The effects of seasonal affective disorder and alcohol abuse on sleep and snoring functions in a population-based study in Finland

Summary

Seasonal affective disorder (SAD) is a recurrent depressive disorder with a seasonal pattern. In addition to some specific symptoms such as sad mood, low energy or carbohydrate craving, this mood disorder is also characterized by the presence of sleeping problems and alcohol disorders. Interestingly, there is a strong link between alcohol use and sleeping deficits. Although previous studies have focused extensively on the sleep patterns in SAD patients and patients with alcohol use disorder (AUD), no research has yet been conducted on subjects with comorbid SAD and AUD. The aim of this study was to examine the differences in sleep functioning between subjects with SAD, AUD and SAD+AUD. A total of 4554 Finnish subjects from the population-based Health 2011 survey were interviewed, and of these 2430 individuals completed all the questionnaires. We selected those participants who fulfilled the criteria for SAD (n = 298), AUD (n = 359), SAD+AUD (n = 69), controls 1 (no current alcohol use, n = 226) and controls 2 (current alcohol use but not AUD, n = 1445). Controls with a history of alcohol abuse were excluded (n = 33). All the participants completed the EuroQoL five-dimensions questionnaire (EQ-5), the Seasonal Pattern Assessment Questionnaire (SPAQ), the Alcohol Use Disorders Identification Test (AUDIT) and several questions about sleeping, based on the Basic Nordic Sleep Questionnaire (BNSQ). Our results showed that those subjects with SAD+AUD reported the highest levels of subjective sleeping problems compared to controls, SAD and AUD. These findings suggest the relevance of examining the comorbidity of SAD and AUD when studying sleep functioning in these groups of patients.

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Differences in Energy Consumption in Electric Vehicles: An Exploratory Real-World Study in Beijing

Electric vehicles (EVs) are widely regarded as a promising solution to reduce air pollution in cities and key to a low carbon mobility future. However, their environmental benefits depend on the temporal and spatial context of actual usage (journey energy efficiency) and the rolling out of EVs is complicated by issues such as limited range. This paper explores how the energy efficiency of EVs is affected and shaped by driving behavior, personal driving styles, traffic conditions, and infrastructure design in the real world. Tests have been conducted with a Nissan LEAF under a typical driving cycle on the Beijing road network in order to improve understanding of variations in energy efficiency among drivers under different urban traffic conditions. Energy consumption and operation parameters were recorded in both peak and off-peak hours for a total of 13 drivers. The analysis reported in this paper shows that there are clear patterns in energy consumption along a route that are in part related to differences in infrastructure design, traffic conditions, and personal driving styles. The proposed method for analyzing time series data about energy consumption along routes can be used for research with larger fleets of EVs in the future.

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Hydraulic performance and fouling characteristics of a membrane sequencing batch reactor (MSBR) for landfill leachate treatment under various operating conditions

Abstract

This study investigates the hydraulic performance and the fouling characteristics of a bench-scale membrane sequencing batch reactor (MSBR), treating mature landfill leachate under various time-based operating conditions. The MSBR system operated initially under a high-flux condition (Period 1) which resulted in a rapid trans-membrane pressure (TMP) rise due to intense fouling. Following the characterization of Period 1 as super-critical, the system was subsequently operated under a near-critical condition (Period 2). The overall filtration resistance analysis showed that cake layer formation was the dominant fouling mechanism during Period 1, contributing to 85.5% of the total resistance. However, regarding the MSBR operation during Period 2, adsorption was found to also be a dominant fouling mechanism (Days 1 to 47), contributing to 29.1% of the total resistance. Additionally, the irregular total resistance variation, which was observed during the subsequent operation (Days 48 to 75), and the respective filtration resistance analysis suggested also the formation of an initial sludge cake layer on the membrane surface, contributing to the 47.7% of the total resistance.

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Intracellular B Lymphocyte Signalling and the Regulation of Humoral Immunity and Autoimmunity

Abstract

B lymphocytes are critical for effective immunity; they produce antibodies and cytokines, present antigens to T lymphocytes and regulate immune responses. However, because of the inherent randomness in the process of generating their vast repertoire of antigen-specific receptors, B cells can also cause diseases through recognizing and reacting to self. Therefore, B lymphocyte selection and responses require tight regulation at multiple levels and at all stages of their development and activation to avoid diseases. Indeed, newly generated B lymphocytes undergo rigorous tolerance mechanisms in the bone marrow and, subsequently, in the periphery after their migration. Furthermore, activation of mature B cells is regulated through controlled expression of co-stimulatory receptors and intracellular signalling thresholds. All these regulatory events determine whether and how B lymphocytes respond to antigens, by undergoing apoptosis or proliferation. However, defects that alter regulated co-stimulatory receptor expression or intracellular signalling thresholds can lead to diseases. For example, autoimmune diseases can result from altered regulation of B cell responses leading to the emergence of high-affinity autoreactive B cells, autoantibody production and tissue damage. The exact cause(s) of defective B cell responses in autoimmune diseases remains unknown. However, there is evidence that defects or mutations in genes that encode individual intracellular signalling proteins lead to autoimmune diseases, thus confirming that defects in intracellular pathways mediate autoimmune diseases. This review provides a synopsis of current knowledge of signalling proteins and pathways that regulate B lymphocyte responses and how defects in these could promote autoimmune diseases. Most of the evidence comes from studies of mouse models of disease and from genetically engineered mice. Some, however, also come from studying B lymphocytes from patients and from genome-wide association studies. Defining proteins and signalling pathways that underpin atypical B cell response in diseases will help in understanding disease mechanisms and provide new therapeutic avenues for precision therapy.

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The role of the neural niche in brain metastasis

Abstract

Cancers with neurologic metastasis are a burdensome affliction. As primary cancer care improves, the incidence of metastatic cancer increases as a result of prolonged survival time. Because of this, advances in the understanding of the mechanisms of metastasis are important for the development of continuing management strategies. Knowing how metastatic tumor cells engage, survive, and proliferate in the central nervous system (CNS) is an important first step in developing treatment paradigms. The neural niche is the soil of the CNS that accommodates tumor cells, is a microenvironment of cell signaling that exists between the tumor cell and the native neural cellular network. Elements of the neural niche have been identified as acquaintances for metastatic tumor growth. As more is known about the neural niche, treatment strategies can be developed to target these networks of metastatic tumor progression.

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The role of the neural niche in brain metastasis

Abstract

Cancers with neurologic metastasis are a burdensome affliction. As primary cancer care improves, the incidence of metastatic cancer increases as a result of prolonged survival time. Because of this, advances in the understanding of the mechanisms of metastasis are important for the development of continuing management strategies. Knowing how metastatic tumor cells engage, survive, and proliferate in the central nervous system (CNS) is an important first step in developing treatment paradigms. The neural niche is the soil of the CNS that accommodates tumor cells, is a microenvironment of cell signaling that exists between the tumor cell and the native neural cellular network. Elements of the neural niche have been identified as acquaintances for metastatic tumor growth. As more is known about the neural niche, treatment strategies can be developed to target these networks of metastatic tumor progression.

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Natriuretic peptides in the control of lipid metabolism and insulin sensitivity

Summary

Natriuretic peptides have long been known for their cardiovascular function. However, a growing body of evidence emphasizes the role of natriuretic peptides in human substrate and energy metabolism, thereby connecting the heart with several insulin-sensitive organs like adipose tissue, skeletal muscle and liver. Obesity may be associated with an impaired regulation of the natriuretic peptide system, also indicated as a natriuretic handicap. Evidence points towards a contribution of this natriuretic handicap to the development of obesity, type 2 diabetes mellitus and cardiometabolic complications, although the causal relationship is not fully understood. Nevertheless, targeting the natriuretic peptide pathway may improve metabolic health in obesity and type 2 diabetes mellitus. This review will focus on current literature regarding the metabolic roles of natriuretic peptides with emphasis on lipid metabolism and insulin sensitivity. Furthermore, it will be discussed how exercise and lifestyle intervention may modulate the natriuretic peptide-related metabolic effects.

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Effectiveness of Adenotonsillectomy and Risk of Velopharyngeal Insufficiency in Children With Prader-Willi Syndrome

Annals of Otology, Rhinology &Laryngology, Ahead of Print.


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Successful Placement of a BAHA Implant in a Patient With Epidermolysis Bullosa: A Case Report and Review of the Literature

Annals of Otology, Rhinology &Laryngology, Ahead of Print.


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Intraductal Laser Fiber Tip Fracture and Retrieval During Sialendoscopic Laser-Assisted Lithotripsy

Annals of Otology, Rhinology &Laryngology, Ahead of Print.


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Sleep bruxism: validity of diagnostic tools

This review of diagnostic tools for sleep bruxism included 8 studies the majority being at high risk of bias. Portable diagnostic devices had best validity but quality of evidence was very-low to moderate.

The post Sleep bruxism: validity of diagnostic tools appeared first on National Elf Service.

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New research on probiotics in the prevention and treatment of colon cancer

In an innovative approach to colorectal cancer (CRC) prevention and treatment, scientists are studying ways to replace missing metabolites in patients prone to gut inflammation and CRC. A new study in The American Journal of Pathology describes how...

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Mosasaurs and snakes have a periodontal ligament: timing and extent of calcification, not tissue complexity, determines tooth attachment mode in reptiles

Abstract

Squamates present a unique challenge to our understanding of dental evolution in amniotes because they are the only extant tooth-bearing group for which a ligamentous tooth attachment is considered to be absent. This has led to the assumption that mammals and crocodilians have convergently evolved a ligamentous tooth attachment, composed of root cementum, periodontal ligament, and alveolar bone, whereas squamates are thought to possess a single bone of attachment tissue that fuses teeth to the jaws. The identity and homology of tooth attachment tissues between squamates, crocodilians, and mammals have thus been a focal point of debate for decades. We provide a novel interpretation of the mineralized attachment tissues in two focal taxa in this debate, mosasaurids and snakes, and compare dental tissue histology with that of the extant crocodilian Caiman sclerops. We identify a periodontal ligament in these squamates that usually exists temporarily as a soft connective tissue anchoring each tooth to the alveolar bone. We also identify two instances where complete calcification of the periodontal ligament does not occur: in a durophagous mosasaur, and in the hinged teeth of fossil and modern snakes. We propose that the periodontal ligament rapidly calcifies in the majority of mosasaurids and snakes, ankylosing the tooth to the jaw. This gives the appearance of a single, bone-like tissue fusing the tooth to the jaw in ankylosed teeth, but is simply the end stage of dental tissue ontogeny in most snakes and mosasaurids.

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Mike Nugent's - crowning' achievement

After the drill is gone: Mike Nugent was the model for the illustration on the Oc. 19, 1957 cover of the 'Saturday Evening Post.'

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Marine microbiology: Algal virus boosts nitrogen uptake in the ocean

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Issue Information - Contents

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Cover Image

The cover image, by Miklos Perenyei et al., is based on the Operative Techniques Use of the self-retaining Alexis ring retractor in transoral robotic surgery, DOI: 10.1002/hed.24882.

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Cover Image

The cover image, by Miklos Perenyei et al., is based on the Operative Techniques Use of the self-retaining Alexis ring retractor in transoral robotic surgery, DOI: 10.1002/hed.24882.

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Issue Information - Contents

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DNA aptamer generation by ExSELEX using genetic alphabet expansion with a mini-hairpin DNA stabilization method

Publication date: Available online 13 September 2017
Source:Biochimie
Author(s): Ichiro Hirao, Michiko Kimoto, Kyung Hyun Lee
A novel aptamer generation method to greatly augment the affinity and stability of DNA aptamers was developed by genetic alphabet expansion combined with mini-hairpin DNA technology. The genetic alphabet expansion increases the physicochemical and structural diversities of DNA aptamers by introducing extra components, unnatural bases, as a fifth base, allowing for the enhancement of DNA aptamer affinities. Furthermore, the mini-hairpin DNA technology stabilizes DNA aptamers against nuclease digestion and thermal denaturation, by introducing an extraordinarily stable mini-hairpin DNA containing a GCGAAGC sequence. This novel method provides stabilized high-affinity DNA aptamers for diagnostic and therapeutic applications.

Graphical abstract

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On the importance of protein diffusion in biological systems: The example of the Bicoid morphogen gradient

Publication date: Available online 13 September 2017
Source:Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
Author(s): Cécile Fradin
Morphogens are proteins that form concentration gradients in embryos and developing tissues, where they act as postal codes, providing cells with positional information and allowing them to behave accordingly. Bicoid was the first discovered morphogen, and remains one of the most studied. It regulates segmentation in flies, forming a striking exponential gradient along the anterior-posterior axis of early Drosophila embryos, and activating the transcription of multiple target genes in a concentration-dependent manner. In this review, the work done by us and by others to characterize the mobility of Bicoid in D. melanogaster embryos is presented. The central role played by the diffusion of Bicoid in both the establishment of the gradient and the activation of target genes is discussed, and placed in the context of the need for these processes to be all at once rapid, precise and robust. The Bicoid system, and morphogen gradients in general, remain amongst the most amazing examples of the coexistence, often observed in living systems, of small-scale disorder and large-scale spatial order. This article is part of a Special Issue entitled: Biophysics in Canada, edited by Lewis Kay, John Baenziger, Albert Berghuis and Peter Tieleman.

Graphical abstract

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Effects of physical activity calorie expenditure (PACE) labeling: study design and baseline sample characteristics

Obesity and physical inactivity are responsible for more than 365,000 deaths per year and contribute substantially to rising healthcare costs in the US, making clear the need for effective public health interv...

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Nationwide cross-sectional survey of schistosomiasis and soil-transmitted helminthiasis in Sudan: study protocol

Schistosomiasis and soil-transmitted helminthiasis (STHs) are target neglected tropical diseases (NTDs) of preventive chemotherapy, but the control and elimination of these diseases have been impeded due to re...

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Neighborhood-resources for the development of a strong SOC and the importance of understanding why and how resources work: a grounded theory approach

Providing individuals with psychosocial resources such as sense of coherence (SOC) seems a beneficial strategy for health promotion in the neighborhood. In order to become a supporting theory for health promot...

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Is economic environment associated with the physical activity levels and obesity in Chinese adults? A cross-sectional study of 30 regions in China

Based on the 2014 survey of physical activity and physical fitness data of 20 − 69 year old Chinese, this study aims to investigate the relationship between economic development and people's physical activity ...

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Preface to glyco-neuroscience

Publication date: October 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1861, Issue 10





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In vivo multimodal tumor imaging and photodynamic therapy with novel theranostic agents based on the porphyrazine framework-chelated gadolinium (III) cation

Publication date: Available online 13 September 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Diana V. Yuzhakova, Svetlana A. Lermontova, Ilya S. Grigoryev, Maria S. Muravieva, Alena I. Gavrina, Marina V. Shirmanova, Irina V. Balalaeva, Larisa G. Klapshina, Elena V. Zagaynova
BackgroundA promising strategy for cancer diagnosis and therapy is the development of an agent for multimodal imaging and treatment. In the present paper we report on two novel multifunctional agents prepared on the porphyrazine pigment platform using a gadolinium (III) cation chelated by red-fluorescent tetrapyrrole macrocycles (GdPz1 and GdPz2).MethodsSpectral and magnetic properties of the compounds were analyzed. Monitoring of GdPz1 and GdPz2 accumulation in the murine colon carcinoma CT26 was performed in vivo using fluorescence imaging and MRI. The photobleaching of GdPz1 or GdPz2 and tumor growth rate after photodynamic therapy (PDT) were assessed.ResultsGdPz1 and GdPz2 demonstrated the selective accumulation in tumor that was indicated by higher fluorescence intensity in the tumor area in comparison with the normal tissues. The results of MRI in vivo showed that GdPz1 or GdPz2 provided significant contrast enhancement of the tumor in T1 MR images. PDT with GdPz2 resulted in ~20% decrease in fluorescence intensity of the compound and the inhibition of tumor growth.ConclusionsWe assessed the efficiency of two innovative Gd(III) cation-porphyrazine chelates as bimodal MR and fluorescent probes and photosensitizers for PDT and showed their potentials for tumor diagnostics and treatment.General significanceWater-soluble structures simple in preparation and administration into the body represent special interest for theranostics of tumors. Novel porphyrazine macrocycles chelating a central gadolinium cation demonstrated a good prospect as effective multimodal agents, representing a new approach to MRI and fluorescence imaging guided PDT.



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Nintedanib selectively inhibits the activation and tumour-promoting effects of fibroblasts from lung adenocarcinoma patients

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Associations of Helicobacter pylori infection and chronic atrophic gastritis with accelerated epigenetic ageing in older adults

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Crosstalk between TEMs and endothelial cells modulates angiogenesis and metastasis via IGF1-IGF1R signalling in epithelial ovarian cancer

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Albumin, bilirubin, uric acid and cancer risk: results from a prospective population-based study

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Estimating the impact of a cancer diagnosis on life expectancy by socio-economic group for a range of cancer types in England

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Circulating cytokines and small molecules follow distinct expression patterns in acute myeloid leukaemia

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The American Academy of Oral Medicine Clinical Practice Statement: Somatic symptom and related disorders

Publication date: Available online 12 September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology





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Multiple mechanisms contribute to increased neutral lipid accumulation in yeast producing recombinant variants of plant diacylglycerol acyltransferase 1 [Lipids]

The apparent bottleneck in the accumulation of oil during seed development in some oleaginous plant species is the formation of triacylglycerol (TAG) by the acyl-CoA-dependent acylation of sn-1,2- diacylglycerol catalyzed by diacylglycerol acyltransferase (DGAT, EC 2.3.1.20). Improving DGAT activity using protein engineering could lead to improvements in seed oil yield, for example in canola-type Brassica napus. Directed evolution of B. napus DGAT1 (BnaDGAT1) previously revealed that one of the regions where amino acid residue substitutions leading to higher performance in BnaDGAT1 was in the ninth predicted transmembrane domain (PTMD9). In this study, several BnaDGAT1 variants with amino acid residue substitutions in PTMD9 were characterized. Among these enzyme variants, the extent of yeast TAG production was affected by different mechanisms including increased enzyme activity, increased polypeptide accumulation and possibly reduced substrate inhibition. The kinetic properties of the BnaDGAT1 variants were affected by the amino acid residue substitutions and a new kinetic model based on substrate inhibition and sigmoidicity was generated. Based on sequence alignment and further biochemical analysis, the amino acid residue substitutions that conferred increased TAG accumulation were shown to be present in the DGAT1-PTMD9 region of other higher plant species. When amino acid residue substitutions that increased BnaDGAT1 enzyme activity were introduced into recombinant Camelina sativa DGAT1, they also improved enzyme performance. Thus, the knowledge generated from directed evolution of DGAT1 in one plant species can be transferred to other plant species and has potentially broad applications in genetic engineering of oleaginous crops and microorganisms.

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Nucleolar and spindle-associated protein 1 (NUSAP1) interacts with a SUMO E3 ligase complex during chromosome segregation [Cell Biology]

The mitotic spindle is composed of dynamic microtubules and associated proteins that together direct chromosome movement during mitosis. The spindle plays a vital role in accurate chromosome segregation fidelity and is a therapeutic target in cancer. Nevertheless, the molecular mechanisms by which many spindle associated proteins function remains unknown. The Nucleolar and Spindle Associated Protein NUSAP1 is a microtubule binding protein implicated in spindle stability and chromosome segregation. We show here that NUSAP1 localizes to dynamic spindle microtubules in a unique chromosome-centric pattern, in the vicinity of overlapping microtubules, during metaphase and anaphase of mitosis. Mass spectrometry based analysis of endogenous NUSAP1 interacting proteins uncovered a cell cycle regulated interaction between the RanBP2-RanGAP1-UBC9 SUMO E3 ligase complex and NUSAP1. Like NUSAP1 depletion, RanBP2 depletion impaired the response of cells to the microtubule poison taxol. NUSAP1 contains a conserved SAP domain (SAF-A/B, Acinus and PIAS). SAP domains are common among many other SUMO E3s, and are implicated substrate recognition and ligase activity. We speculate that NUSAP1 contributes to accurate chromosome segregation by acting as a co-factor for RanBP2-RanGAP1-UBC9 during cell division.

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The metal chaperone Atox1 regulates the activity of the human copper transporter ATP7B by modulating domain dynamics. [Enzymology]

The human transporter ATP7B delivers copper to the biosynthetic pathways and maintains copper homeostasis in the liver. Mutations in ATP7B cause the potentially fatal hepato-neurological disorder Wilson disease. The activity and intracellular localization of ATP7B are regulated by copper, but the molecular mechanism of this regulation is largely unknown. We show that the copper chaperone Atox1, which delivers copper to ATP7B, and the group of the first three metal binding domains (MBD1-3) are central to the activity regulation of ATP7B. Atox1-Cu binding to ATP7B changes domain dynamics and interactions within the MBD1-3 group, and activates ATP hydrolysis. To understand the mechanism linking Atox1-MBD interactions and enzyme activity, we have determined the MBD1-3 conformational space using SAXS, and identified changes in MBD dynamics caused by apo-Atox1 and Atox1-Cu by solution NMR. The results show that copper transfer from Atox1 decreases domain interactions within the MBD1-3 group and increases the mobility of the individual domains. The N-terminal segment of MBD1-3 was found to interact with the nucleotide-binding domain of ATP7B, thus physically coupling the domains involved in copper binding and those involved in ATP hydrolysis. Taken together, the data suggest a regulatory mechanism, in which Atox1-mediated Cu-transfer activates ATP7B by releasing inhibitory constraints through increased freedom of MBD1-3 motions.

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SOCS1 is an inducible negative regulator of IFN lambda induced gene expression in vivo [Signal Transduction]

Type I (α and β) and type III (λ) interferons (IFNs) are induced upon viral infection through host sensory pathways that activate IFN regulatory factors (IRFs) and nuclear factor κB. Secreted IFNs induce autocrine and paracrine signalling through the JAK-Stat pathway leading to the transcriptional induction of hundreds of IFN stimulated genes (ISGs), amongst them sensory pathway components such as cGAS, STING, RIG-I, MDA5 and the transcription factor IRF7 that enhance the induction of IFNαs and IFNλss. This positive feedback loop enables a very rapid and strong host response, which at some point has to be controlled by negative regulators to maintain tissue homeostasis. Type I IFN signalling is controlled by the inducible negative regulators suppressor of cytokine signalling 1 (SOCS1), SOCS3 and ubiquitin-specific peptidase 18 (USP18). The physiological role of these proteins in IFNλ signalling has not been clarified. Here we used knockout cell lines and mice to show that IFNλ signalling is regulated by SOCS1, but not by SOCS3 or USP18. These differences were the basis for distinct kinetic properties of type I and III IFNs. We found that IFNα signalling is transient and becomes refractory after hours, whereas IFNλ provides a long-lasting ISG induction.

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High-resolution structure of a lytic polysaccharide monooxygenase from Hypocrea jecorina reveals a predicted linker as an integral part of the catalytic domain [Molecular Biophysics]

For decades, the enzymes of the fungus Hypocrea jecorina have served as a model system for the breakdown of cellulose. Three-dimensional structures for almost all H. jecorina cellulose-degrading enzymes are available, except for HjLPMO9A, belonging to the AA9 family of lytic polysaccharide monooxygenases (LPMOs). These enzymes enhance the hydrolytic activity of cellulases and are essential for cost-efficient conversion of lignocellulosic biomass. Here, using structural and spectroscopic analyses, we found that native HjLPMO9A contains a catalytic domain and a family-1 carbohydrate-binding module (CBM1) connected via a linker sequence. A C-terminally truncated variant of HjLPMO9A containing 21 residues of the predicted linker expressed at levels sufficient for analysis. Here, using structural, spectroscopic and biochemical analyses, we found that this truncated variant exhibited reduced binding to and activity on cellulose compared with the full-length enzyme. Importantly, a 0.95 Å resolution X-ray structure of truncated HjLPMO9A revealed that the linker forms an integral part of the catalytic domain structure, covering a hydrophobic patch on the catalytic AA9 module. We noted that the oxidized catalytic center contains a Cu(II) coordinated by two His ligands, one of which has a Hisbrace in which the His1 terminal amine group also coordinates to a copper. The final equatorial position of the Cu(II) is occupied by a water-derived ligand. The spectroscopic characteristics of the truncated variant were not measurably different from those of full-length HjLPMO9A, indicating that the presence of the CBM1 module increases the affinity of HjLPMO9A for cellulose binding, but does not affect the active site.

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ZNF143 is an important regulator of the myeloid transcription factor C/EBP{alpha} [Gene Regulation]

The transcription factor (TF) C/EBPα is essential for myeloid differentiation and is frequently dysregulated in acute myeloid leukemia (AML). While studied extensively, the precise regulation of its gene by upstream factors has remained largely elusive. Here, we investigated its transcriptional activation during myeloid differentiation. We identified an evolutionarily conserved octameric sequence, CCCAGCAG, approximately 100 bases upstream of the CEBPA transcription start site (TSS), and demonstrated through mutational analysis that this sequence is crucial for C/EBPα expression. This sequence is present in the genes encoding C/EBPα in humans, rodents, chicken and frog, and is also present in the promoters of other C/EBP family members. We identified that ZNF143, the human homolog of the Xenopus transcriptional activator STAF, specifically binds to this 8bp sequence to activate C/EBPα expression in myeloid cells through a mechanism that is distinct from that observed in liver cells and adipocytes. Altogether, our data suggests that ZNF143 plays an important role in the expression of C/EBPα in myeloid cells.

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Beta-catenin directs the transformation of testis Sertoli cells to ovarian granulosa-like cells by inducing Foxl2 expression [Gene Regulation]

Sertoli and granulosa cells are two major types of somatic cells in the male and female gonads,respectively. Previous studies have shown that Sertoli and granulosa cells are derived from common progenitor cells and that differentiation of these two cell types is regulated by sex differentiation genes. The signaling pathway including the adhesion and transcription factor Ctnnb1 (cadherin-associated protein, beta 1, also known as β-catenin) regulates differentiation of granulosa cells in the absence of the transcription factor Sry, and over-activation of β-catenin in the presence of Sry leads to granulosa prior to sex determination. Surprisingly, our previous study found that β-catenin over-activation in Sertoli cells after sex determination can also cause disruption of the testicular cord and aberrant testis development. However, the underlying molecular mechanism was unclear. In this study, we found that constitutive activation of Ctnnb1 in Sertoli cells led to ectopic expression of the granulosa cell-specific marker FOXL2 in testes. Co-staining experiments revealed that FOXL2-positive cells were derived from Sertoli cells, and Sertoli cells were transformed into granulosa-like cells after Ctnnb1 over-activation. Further studies demonstrated that CTNNB1 induced Foxl2 expression by directly binding to transcription factor Tcf/Lef binding sites in the FOXL2 promoter region. We also found that directly over-expression of Foxl2 indecreased the expression of Sertoli cell-specific genes in primary Sertoli cells. Taken together, these results demonstrate that repression of β-catenin (CTNNB1) signaling is required for lineage maintenance of Sertoli cells. Our study provides a new mechanism for Sertoli cell lineage maintenance during gonad development.

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Polo-like kinase 1 (Plk1) overexpression enhances ionizing radiation-induced cancer formation in mice [Signal Transduction]

Polo-like kinase 1 (Plk1), a serine/threonine protein kinase normally expressed in mitosis, is frequently upregulated in multiple types of human tumors regardless of the cell cycle stage. However, the causal relationship between Plk1 upregulation and tumorigenesis is incompletely investigated. To this end, using a conditional expression system, here we generated Plk1 transgenic mouse lines to examine Plk1 role in tumorigenesis. Plk1 overexpression in mouse embryonic fibroblasts prepared from the transgenic mice led to aberrant mitosis followed by aneuploidy and apoptosis. Surprisingly, Plk1 overexpression had no apparent phenotypes in the mice. Given that no malignant tumor formation was observed even after a long period of Plk1 overexpression, we reasoned that additional factors are required for tumorigenesis in Plk1-overexpressing mice. Because Plk1 can directly participate in the regulation of the DNA damage response (DDR) pathway, we challenged Plk1-overexpressing mice with ionizing radiation (IR) and found that Plk1-overexpressing mice are much more sensitive to IR than their wild type littermates. Analysis of tumor development in the Plk1-overexpressing mice indicated a marked decrease in the time required for tumor emergence after IR. At the molecular level, Plk1 overexpression led to reduced phosphorylation of the serine/threonine kinases ATM and Chk2 and of histone H2AX after IR treatment both in vivo and in vitro. Furthermore, RNA-Seq analysis suggested that Plk1 elevation decreases the expression of several DDR genes. We conclude that Plk1 overexpression may contribute to tumor formation by both inducing chromosomal instability and suppressing the DDR pathway.

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Prion protein is required for tumor necrosis factor alpha (TNF{alpha})-triggered nuclear factor kappa B (NF-{kappa}B) signaling and cytokine production [Signal Transduction]

The expression of normal cellular prion protein (PrP) is required for the pathogenesis of prion diseases. However, the physiological functions of PrP remain ambiguous. Here, we identified PrP as being critical for tumor necrosis factor (TNF)α-triggered signaling in a human melanoma cell line, M2, and a pancreatic ductal cell adenocarcinoma cell line, BxPC-3. In M2 cells, TNFα upregulates the expression of p-I-kappa-B-kinase α/β (p-IKKα/β), p-p65, and p-JNK, but downregulates the IκBα protein, all of which are downstream signaling intermediates in the TNF receptor signaling cascade. When PRNP is deleted in M2 cells, the effects of TNFα are no longer detectable. More importantly, p-p65 and p-JNK responses are restored when PRNP is reintroduced into the PRNP null cells. TNFα also activates NF-κB and increases TNFα production in wildtype M2 cells, but not in PrP-null M2 cells. Similar results are obtained in the BxPC-3 cells. Moreover, TNFα activation of NF-κB requires ubiquitination of receptor-interacting serine/threonine kinase 1 (RIP1) and TNF receptor-associated factor 2 (TRAF2). TNFα treatment increases the binding between PrP and the deubiquitinase tumor suppressor cylindromatosis (CYLD), in these treated cells, binding of CYLD to RIP1 and TRAF2 is reduced. We conclude that PrP traps CYLD, preventing it from binding and deubiquitinating RIP1 and TRAF2. Our findings reveal that PrP enhances the responses to TNFα, promoting proinflammatory cytokine production, which may contribute to inflammation and tumorigenesis.

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Proceedings of the Pulp Biology and Regeneration Group Symposium 2016: “Dental Regenerative Medicine and Functional Dental Longevity”

Advances in modern medicine have dramatically increased life expectancy and reduced morbidity. There is an increasing need to promote greater functional dental longevity to benefit patients with the maintenance of their natural dentition throughout life. Regenerative therapies are an integral part of modern medicine that have revolutionized patient care. The incorporation of regenerative principles in dentistry has been far less seamless. Despite advances in dental materials, instruments and techniques, that have transformed many areas of dentistry, including endodontics, there is still the need to improve clinical outcomes and predictability.

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Clinical utility of self-disclosure for adults who stutter: Apologetic versus informative statements

Publication date: Available online 12 September 2017
Source:Journal of Fluency Disorders
Author(s): Courtney T. Byrd, Robyn Croft, Zoi Gkalitsiou, Elizabeth Hampton
PurposeThe purpose of the present study was to explore the clinical utility of self-disclosure, particularly, whether disclosing in an informative manner would result in more positive observer ratings of the speaker who stutters than either disclosing in an apologetic manner or choosing not to self-disclose at all.MethodObservers (N=338) were randomly assigned to view one of six possible videos (i.e., adult male informative self-disclosure, adult male apologetic self-disclosure, adult male no self-disclosure, adult female informative self-disclosure, adult female apologetic self-disclosure, adult female no self-disclosure). Observers completed a survey assessing their perceptions of the speaker they viewed immediately after watching the video.ResultsResults suggest that self-disclosing in an informative manner leads to significantly more positive observer ratings than choosing not to self-disclose. In contrast, use of an apologetic statement, for the most part, does not yield significantly more positive ratings than choosing not to self-disclose.ConclusionClinicians should recommend their clients self-disclose in an informative manner to facilitate more positive observer perceptions.



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Effects of aging and resistance training in rat tendon remodeling [Research]

In elderly persons, weak tendons contribute to functional limitations, injuries, and disability, but resistance training can attenuate this age-related decline. We evaluated the effects of resistance training on the extracellular matrix (ECM) of the calcaneal tendon (CT) in young and old rats and its effect on tendon remodeling. Wistar rats aged 3 mo (young, n = 30) and 20 mo (old, n = 30) were divided into 4 groups: young sedentary, young trained, old sedentary (OS), and old trained (OT). The training sessions were conducted over a 12-wk period. Aging in sedentary rats showed down-regulation in key genes that regulated ECM remodeling. Moreover, the OS group showed a calcification focus in the distal region of the CT, with reduced blood vessel volume density. In contrast, resistance training was effective in up-regulating connective tissue growth factor, VEGF, and decorin gene expression in old rats. Resistance training also increased proteoglycan content in young and old rats in special small leucine-rich proteoglycans and blood vessels and prevented calcification in OT rats. These findings confirm that resistance training is a potential mechanism in the prevention of aging-related loss in ECM and that it attenuates the detrimental effects of aging in tendons, such as ruptures and tendinopathies.—Marqueti, R. C., Durigan, J. L. Q., Oliveira, A. J. S., Mekaro, M. S., Guzzoni, V., Aro, A. A., Pimentel, E. R., Selistre-de-Araujo, H. S. Effects of aging and resistance training in rat tendon remodeling.

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Tet1 overexpression leads to anxiety-like behavior and enhanced fear memories via the activation of calcium-dependent cascade through Egr1 expression in mice [Research]

Ten-eleven translocation methylcytosine dioxygenase 1 (Tet1) initiates DNA demethylation by converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) at CpG-rich regions of genes, which have key roles in adult neurogenesis and memory. In addition, the overexpression of Tet1 with 5-hmC alteration in patients with psychosis has also been reported, for instance in schizophrenia and bipolar disorders. The mechanism underlying Tet1 overexpression in the brain; however, is still elusive. In the present study, we found that Tet1-transgenic (Tet1-TG) mice displayed abnormal behaviors involving elevated anxiety and enhanced fear memories. We confirmed that Tet1 overexpression affected adult neurogenesis with oligodendrocyte differentiation in the hippocampal dentate gyrus of Tet1-TG mice. In addition, Tet1 overexpression induced the elevated expression of immediate early genes, such as Egr1, c-fos, Arc, and Bdnf, followed by the activation of intracellular calcium signals (i.e., CamKII, ERK, and CREB) in prefrontal and hippocampal neurons. The expression of GABA receptor subunits (Gabra2 and Gabra4) fluctuated in the prefrontal cortex and hippocampus. We evaluated the effects of Tet1 overexpression on intracellular calcium-dependent cascades by activating the Egr1 promoter in vitro. Tet1 enhanced Egr1 expression, which may have led to alterations in Gabra2 and Gabra4 expression in neurons. Taken together, we suggest that the Tet1 overexpression in our Tet1-TG mice can be applied as an effective model for studying various stress-related diseases that show hyperactivation of intracellular calcium-dependent cascades in the brain.—Kwon, W., Kim, H.-S., Jeong, J., Sung, Y., Choi, M., Park, S., Lee, J., Jang, S., Kim, S. H., Lee, S., Kim, M. O., Ryoo, Z. Y. Tet1 overexpression leads to anxiety-like behavior and enhanced fear memories via the activation of calcium-dependent cascade through Egr1 expression in mice.

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Pronounced energy restriction with elevated protein intake results in no change in proteolysis and reductions in skeletal muscle protein synthesis that are mitigated by resistance exercise [Research]

Preservation of lean body mass (LBM) may be important during dietary energy restriction (ER) and requires equal rates of muscle protein synthesis (MPS) and muscle protein breakdown (MPB). Currently, the relative contribution of MPS and MPB to the loss of LBM during ER in humans is unknown. We aimed to determine the impact of dietary protein intake and resistance exercise on MPS and MPB during a controlled short-term energy deficit. Adult men (body mass index, 28.6 ± 0.6 kg/m²; age 22 ± 1 yr) underwent 10 d of 40%-reduced energy intake while performing unilateral resistance exercise and consuming lower protein (1.2 g/kg/d, n = 12) or higher protein (2.4 g/kg per d, n = 12). Pre- and postintervention testing included dual-energy X-ray absorptiometry, primed constant infusion of ring-[¹³C₆]phenylalanine, and ¹⁵[N]phenylalanine to measure acute postabsorptive MPS and MPB; D₂O to measure integrated MPS; and gene and protein expression. There was a decrease in acute MPS after ER (higher protein, 0.059 ± 0.006 to 0.051 ± 0.009%/h; lower protein, 0.061 ± 0.005–0.045 ± 0.006%/h; P < 0.05) that was attenuated with resistance exercise (higher protein, 0.067 ± 0.01%/h; lower protein, 0.061 ± 0.006%/h), and integrated MPS followed a similar pattern. There was no change in MPB (energy balance, 0.080 ± 0.01%/hr; ER rested legs, 0.078 ± 0.008%/hr; ER exercised legs, 0.079 ± 0.006%/hr). We conclude that a reduction in MPS is the main mechanism that underpins LBM loss early in ER in adult men.—Hector, A. J., McGlory, C., Damas, F., Mazara, N., Baker, S. K., Phillips, S. M. Pronounced energy restriction with elevated protein intake results in no change in proteolysis and reductions in skeletal muscle protein synthesis that are mitigated by resistance exercise.

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Endothelial cells promote triple-negative breast cancer cell metastasis via PAI-1 and CCL5 signaling [Research]

Endothelial cells (ECs) in the tumor microenvironment have been reported to play a more active role in solid tumor growth and metastatic dissemination than simply providing the physical structure to form conduits for blood flow; however, the involvement of ECs in the process of triple-negative breast cancer (TNBC) metastasis has not been addressed. Here, we demonstrate that ECs—when mixed with TNBC cells—could increase TNBC cell metastatic potency. After treatment with TGF-β to induce endothelial–mesenchymal transition (EMT), TNBC cells could produce plasminogen activator inhibitor-1 (PAI-1) and stimulate the expression and secretion of the chemokine, CCL5, from ECs, which then acts in a paracrine fashion on TNBC cells to enhance their migration, invasion, and metastasis. CCL5, in turn, accelerates TNBC cell secretion of PAI-1 and promotes TNBC cell metastasis, thus forming a positive feedback loop. Moreover, this enhanced metastatic ability is reversible and dependent on CCL5 signaling via the chemokine receptor, CCR5. Of importance, key features of this pathway are manifested in patients with TNBC and in The Cancer Genome Atlas database. Taken together, our results suggest that ECs enhance EMT-induced TNBC cell metastasis via PAI-1 and CCL5 signaling and illustrate the potential of developing new PAI-1– and CCL5-targeting therapy for patients with TNBC.—Zhang, W., Xu, J., Fang, H., Tang, L., Chen, W., Sun, Q., Zhang, Q., Yang, F., Sun, Z., Cao, L., Wang, Y., Guan, X. Endothelial cells promote triple-negative breast cancer cell metastasis via PAI-1 and CCL5 signaling.

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A Carbon Nanotube Optical Reporter Maps Endolysosomal Lipid Flux

ACS Nano

DOI: 10.1021/acsnano.7b04743

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Sleep disordered breathing in Bardet-Biedl Syndrome

Bardet-Biedl Syndrome (BBS) is an autosomal recessive ciliopathy, and obesity is among its defining characteristics. Consequently, the incidence of sleep disordered breathing (SDB) in this population is expected to be high. Due to its relative rarity, the nature of SDB in this population is poorly described. The objective of this study was to review a single institutional experience in the assessment and management of SDB in patients with BBS.

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Sleep disordered breathing in Bardet-Biedl Syndrome

Bardet-Biedl Syndrome (BBS) is an autosomal recessive ciliopathy, and obesity is among its defining characteristics. Consequently, the incidence of sleep disordered breathing (SDB) in this population is expected to be high. Due to its relative rarity, the nature of SDB in this population is poorly described. The objective of this study was to review a single institutional experience in the assessment and management of SDB in patients with BBS.

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Postoperative Delirium in Indian Patients Following Major Abdominal Surgery for Cancer: Risk Factors and Associations

Abstract

Postoperative delirium (POD) is not uncommon following major abdominal surgery with its incidence ranging between five and 51%. As cancer affects disproportionately, the population older than 65 years and as delirium is more common in the elderly, surgical oncology patients are at a higher risk of developing POD. The present study was undertaken to explore the impact and associations of POD in Indian patients undergoing oncological major abdominal surgery. A retrospective review of the electronic medical records in a tertiary cancer care institution of all postoperative patients who had undergone major gastrointestinal gynaecological and urological abdominal surgery for cancer and required psycho-oncology referral was performed. Patient, surgery and postoperative outcome-related data were collected. Statistical analysis was performed using univariate and multivariate logistic regression analysis. Out of 824 patients who underwent major abdominal surgery, 33 patients (4.0%) were diagnosed with POD. In univariate analysis, older age and history of addiction were found to be statistically significantly associated with POD (p < 0.001). Among the postoperative factors, respiratory complications (p < 0.001), sepsis (p < 0.05), ICU stay > 24 h (p < 0.05) and electrolyte impairment (p < 0.05) were the significant associations with the POD. Thirty-day mortality was higher in the POD group (p < 0.05). In multivariate logistic regression analysis, advanced age, addictions, respiratory complications and sepsis were found to be significant associations with POD, p < 0.001. Postoperative delirium is associated with higher mortality. Older age, postoperative respiratory complications and sepsis are common contributory factors of postoperative delirium.

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Computational assessment of model-based wave separation using a database of virtual subjects

Publication date: Available online 12 September 2017
Source:Journal of Biomechanics
Author(s): Bernhard Hametner, Magdalena Schneider, Stephanie Parragh, Siegfried Wassertheurer
The quantification of arterial wave reflection is an important area of interest in arterial pulse wave analysis. It can be achieved by wave separation analysis (WSA) if both the aortic pressure waveform and the aortic flow waveform are known. For better applicability, several mathematical models have been established to estimate aortic flow solely based on pressure waveforms. The aim of this study is to investigate and verify the model-based wave separation of the ARCSolver method on virtual pulse wave measurements.The study is based on an open access virtual database generated via simulations. Seven cardiac and arterial parameters were varied within physiological healthy ranges, leading to a total of 3325 virtual healthy subjects. For assessing the model-based ARCSolver method computationally, this method was used to perform WSA based on the aortic root pressure waveforms of the virtual patients. Asa reference, the values of WSA using both the pressure and flow waveforms provided by the virtual database were taken.The investigated parameters showed a good overall agreement between the model-based method and the reference. Mean differences and standard deviations were −0.05±0.02AU for characteristic impedance, −3.93±1.79mmHg for forward pressure amplitude, 1.37±1.56mmHg for backward pressure amplitude and 12.42±4.88% for reflection magnitude.The results indicate that the mathematical blood flow model of the ARCSolver method is a feasible surrogate for a measured flow waveform and provides a reasonable way to assess arterial wave reflection non-invasively in healthy subjects.



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A rare cause of acute coronary syndrome in a middle-aged woman: Coronary artery fistula

Biji Soman, Rajan Rajesh, Muneer A Rahaman

Heart India 2017 5(3):130-132

Coronary artery fistula is a rare anomaly of the coronary artery. Majority are congenital, rarely, acquired. Large proportions of these are detected incidentally during evaluation of the coronary artery disease. Most of them remain asymptomatic and do not need any active management, for those who are symptomatic both surgical closure and transcatheter closure devices are available. We present a case of middle-aged woman with a history of hypothyroidism and pulmonary hypertension, who presented with acute coronary syndrome and her coronary angiogram revealed a fistula connecting the left anterior descending artery to pulmonary artery.

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Rupture of noncoronary sinus of Valsalva into right atrium in the fifth decade of life

R Rajan, O Amin, B Soman, R Dashti, M Al Jarallah

Heart India 2017 5(3):125-126

Ruptured noncoronary sinus of Valsalva is a rare condition which was first reported in 1974. The majority of RSOV drains into right-sided chambers and rarely to the left. RSOV is an anatomical defect due to failure of fusion between heart and aortic media with an aneurysmal enlargement which ruptures due to elevated pressures at the aortic root, infective endocarditis, trauma, etc. Here, we are reporting a 57-year-old male diagnosed to have RSOV incidentally. This case report highlights the need for immediate care and prescribing treatment strategies to avoid dreadful complications such as infective endocarditis.

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Outcome of minimal access mitral valve surgery in elderly patients

Sanjay Kumar, David Yuh

Heart India 2017 5(3):111-115

Background: Mitral valve surgery (MVS) approached through sternotomy can be associated with significant morbidity and mortality in the elderly population. The aim of this study was to review our experience with minimal access MVS (mini-mitral) in patients aged 70 years or older. Materials and Methods: A total of 44 patients over the age of 70 years had sternal sparing mini-mitral surgery performed by a single surgeon from January 2011 to November 2015. Results: A total of 44 patients (28 [64%] males and 16 [36%] females), in the age group ranging from 70 to 92 years (mean 79.84 ± 6.52), were included in the study. Comorbidities included hypertension (70.5%; n = 31), peripheral vascular disease (9.1%; n = 4), cerebrovascular disease (11.4%; n = 5), severe chronic obstructive pulmonary disease (2.3%; n = 1), and dialysis-dependent chronic kidney disease (2.3%; n = 1). Five (11.4%) patients had undergone one or more previous cardiac surgery procedures. A total of 33 (75%) patients underwent mitral valve repair, and 11 (25%) underwent replacement with bioprosthesis. Seven (15.9%) required concomitant tricuspid repair and 1 (2.3%) patent foramen ovale closure. Indications for MVS included myxomatous valve (84%; n = 37), ischemic mitral regurgitation (9%; n = 4), and infective endocarditis (7%; n = 3). Eight (18.2%) cases were performed urgently whereas 36 (71.2%) were performed on an elective basis. The median duration of cardiopulmonary bypass and cross-clamp time was 129 and 85 min, respectively. Three (6.8%) had surgery under hypothermic fibrillatory arrest. There were no conversions to median sternotomy and no 30-day mortalities. Postoperative complications included respiratory complications (34%; n = 15), stroke (4.5%; n = 2), acute renal failure (2.3%; n = 1), and reoperation for bleeding (2.3%; n = 1). The median number of hours on mechanical ventilation and hospital stay was 14 h and 7.5 days, respectively. Conclusion: Mini-mitral surgery is safe and feasible with excellent outcomes in the elderly. In our practice, it is the treatment of choice for MVS in elderly patients over the age of 70 years.

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Preface to third issue of Heart India 2017

Alok Kumar Singh

Heart India 2017 5(3):109-110



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Assessing a change for acute myocardial infraction and its risk factors in a rural cohort of northern state of India

D Kumar, SB Sharma, AK Bhardwaj, SK Raina, S Raina

Heart India 2017 5(3):116-121

Background: Rising trend of cardiovascular diseases (CVDs) and associated factors has already substantiated across various population settings. The present study aims to study the degree of change Framingham risk score in a recruited cohort of a rural population in a hilly Northern state of India. Materials and Methods: A prospective cohort study was done where 607 (171 migrated; 19 died) individuals were recruited in the year 2010, and follow-up assessment was done in the year 2015 for change in body mass index, hypertension (HTN), lipid profile, blood sugar, Framingham risk score, and acute myocardial infarction (AMI). Results: Individuals with high systolic blood pressure increased from 32.7% to 47.4%, but a significant decline was found for diastolic HTN (45.3%–34.1%). Obesity increased from 12.7% to 23.7% (P = 0.000). Mean levels of total cholesterol (199.7–187.4 mg/dl) and triglyceride (211.7–153.7 mg/dl) decreased significantly, but decline was not significant for mean low-density lipoprotein. Framingham 10-year risk assessment showed a significant increase (62.0%–73.0%) in individuals with lowest risk score (<1%) and none of individual was observed with high score (>30.0%) neither at the time of recruitment nor at follow-up. Electrocardiography assessment based on rose screening questionnaire observed no signs suggestive of AMI. Conclusion: Recruited cohort observed a slow rise in the development of known risk factor for CVDs such as obesity, systolic HTN, and blood sugar, but without overt manifestations of AMI warranting surveillance for risk factors for CVDs.

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Intermittent complete heart block presenting as recurrent pulmonary edema

S Sulaiman, GN Rajesh, H Vellani

Heart India 2017 5(3):127-129

A middle-aged female presented with recurrent flash pulmonary edema. On evaluation, the patient had apparently stable 2:1 atrioventricular block and a good left ventricular systolic function. Holter recordings revealed intermittent episodes of complete heart block (CHB) precipitating pulmonary edema. The patient underwent permanent pacemaker implantation with complete resolution of symptoms. Isolated recurrent pulmonary edema in CHB is a rare manifestation and has never been reported before.

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Balloon-assisted guide catheter tracking: An innovative technique for anomalous right coronary artery stenting

V Desabandhu, KK Goyal, S Shetty

Heart India 2017 5(3):122-124

The most important factor for a successful percutaneous coronary intervention of an anomalous right coronary artery arising from left sinus is coaxial alignment of guide catheter and adequate backup support. In this report, we describe a novel case in which we used a distally parked balloon to assist in tracking and proper alignment of the guide catheter.

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Double orifice mitral valve

S Khan, V Soni, S Khatri, S Roy

Heart India 2017 5(3):133-135

Double orifice mitral valve (DOMV), is an uncommon anomaly characterized by a mitral valve with a single fibrous annulus with two orifices opening into the left ventricle. Subvalvular structures, especially the tensor apparatus, invariably shows various degrees of abnormalities. DOMV may usually allow normal blood flow between the left atrium and left ventricle but can sometimes substantially obstruct mitral valve inflow or produce mitral valve regurgitation. Recognition of DOMV and awareness of the anatomic variations are important to achieve good therapeutic results. Treatment is only necessary if significant mitral stenosis or mitral regurgitation is present. Here, we present a rare case of DOMV with ventricular septal defect which was detected by two-dimensional echocardiography.

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Role of the IL-12/IL-35 balance in Sjögren’s syndrome

An interferon (IFN) signature is involved in the pathogenesis of primary Sjögren's syndrome (pSS), but whether the signature is type 1 or 2 remains controversial. Mouse models and genetic studies suggested the involvement of T helper 1 and type 2 IFN pathways. Likewise, polymorphisms of interleukin 12A gene (IL-12A), which encodes for IL-12p35, have been associated with pSS. IL-12p35 subunit is shared by 2 heterodimers, IL-12 and IL-35.

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Mast Cell Chymase Decreases The Severity Of Group B Streptococcus Infections

MCPT4-mediated downregulation of fibronectin via proteolytic cleavage contributes to reduced systemic GBS dissemination and preterm birth rates.

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Mast cell exosomes can suppress allergic reactions by binding to IgE

Neutralizing free IgE would appear to be an important strategy for the treatment of allergic diseases. This article explores a novel anti-IgE agent.

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Alveolar eosinophilia in current smokers with chronic obstructive pulmonary disease in the SPIROMICS cohort

Active smoking in stable COPD subjects significantly increased eosinophil accumulation in the distal airspaces, but not in sputum or peripheral blood. Our findings support the need to investigate this cell-type as a potential driver of COPD symptomatology and progression.

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Clinical, Immunological and Genetic Spectrum of 696 Patients with Combined Immunodeficiency

Capsule Summary: In this study of 696 patients with CID, molecular diagnosis was achieved in ∼78% of the patients.

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Estimating Vocal Effort from the Aerodynamics of Labial Fricatives: A Feasibility Study

Vocal effort in loud voice is produced with increased subglottal pressure during vowels and increased supraglottal pressure during consonants. In the paper, our main objective is to check whether it was supported by a parallel increase in the airflow resistance of the laryngeal articulator and of the supralaryngeal articulator, here the lips.

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Tributyltin chloride disrupts aortic vascular reactivity and increases reactive oxygen species production in female rats

Abstract

Organotin compounds, such as tributyltin (TBT), are environment contaminants that induce bioaccumulation and have potential toxic effects on marine species and mammals. TBT have been banned by the International Maritime Organization in 2003. However, the assessment of butyltin and metal contents in marine sediments has demonstrated high residual levels of TBT in some cases exceeding 7000 ng Sn g⁻¹. The acceptable daily intake (ADI) level for TBT established by the World Health Organization is 0.5 μg/kg bw/day is based on genotoxicity, reproduction, teratogenicity, immunotoxicity, and mainly neurotoxicity. However, their effect on the cardiovascular system is not well understood. In this study, female rats were exposed to 0.5 μg/kg/day of TBT for 15 days with the goal of understanding the effect of TBT on vascular function. Female Wistar rats were treated daily by gavage and divided into control (n = 10) and TBT (n = 10) groups. The aortic rings were incubated with phenylephrine in both the presence and absence of endothelium. The phenylephrine concentration–response curves were generated by exposing endothelium-intact samples to N^G-nitro-l-arginine methyl ester (L-NAME), apocynin, superoxide dismutase (SOD), catalase, tiron, and allopurinol. Acetylcholine (ACh) and sodium nitroprusside (SNP) were used to evaluate the relaxation response. Exposure to TBT reduced serum 17β-estradiol E₂ levels and increased vascular reactivity. After incubation with L-NAME, the vascular reactivity to phenylephrine was significantly higher. Apocynin, SOD, catalase, and tiron decreased the vascular reactivity to phenylephrine to a significantly greater extent in TBT-treated rats than in the control rat. The relaxation induced by ACh and SNP was significantly reduced in TBT rats. Exposure to TBT induced aortic wall atrophy and increased superoxide anion production and collagen deposition. These results provide evidence that exposing rats to the current ADI for TBT (0.5 μg/kg) for 15 days induced vascular dysfunction due to oxidative stress and morphological damage and should be considered an important cardiovascular risk factor.

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Aerial application of copper for dothistroma control in New Zealand’s planted forests—effect on stream environments

Abstract

Limited information is available on the risk to aquatic environments from the aerial application of copper fungicides to treat dothistroma needle blight in managed forests. Cuprous oxide was aerially applied to three catchments of Pinus radiata of varying age classes in the central North Island of New Zealand. Copper was monitored in stream water and sediments prior to and for 1 month after application. Copper deposits collected from tracer plates deployed above the water surface along the stream channels within the treated areas at each site ranged from 13 to 406 ppm. Lowest concentrations occurred above small stream channels with dense overhead riparian vegetation. Peak copper concentrations in stream water across the three sites ranged from 28 to 60 μg L⁻¹ and were below the analytical detection limit within hours. Copper concentrations were higher and persisted for longer in stream sediment (range 1.7–6.1 mg kg⁻¹, sampled at two sites only). Copper concentrations in sediments were below environmental guidelines. Copper concentrations in water and sediment indicated a low risk to aquatic organisms based on the exposure times to the concentrations measured in this study.

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Ecotoxicological impact assessment of the brine discharges from a desalination plant in the marine waters of the Algerian west coast, using a multibiomarker approach in a limpet, Patella rustica

Abstract

The aim of our study is to evaluate the impact of Bousfer desalination plant brine discharges on the Algerian west coast, on a natural population of the marine gastropod mollusc Patella rustica. The effects of a chronic exposure to such discharges are complex to understand due to the combined effects of environmental physico-chemical parameters (e.g., high salinity) and different pollutants that can modulate the physiological responses of this species to stress. In this context, we assessed the biological effects in a marine species P. rustica, by a multibiomarker approach that provided information on the health status of organisms in response to such an environmental stress. We measured biomarkers in the whole soft tissues of limpets as indicators of neurotoxicity (AChE activity), oxidative stress (CAT, SOD, GR, and GPx activities), biotransformation (GST), oxidative damage (LPO through TBARS levels), and genotoxicity (CSP 3-like activity). In parallel, hydrological parameters were measured in the Bay of Oran, at four selected sites: site H considered as a "hotspot," located at Bousfer desalination plant; two other sites E and W, at the east and the west of H respectively; finally, site R "reference" located in Madragh, which is considered as a remote clean site. Our analyses revealed that the activities of antioxidant defense enzymes reached the highest levels in P. rustica collected from site H. The activation of antioxidant defense system in these organisms translated the alteration of their status health, reflecting a level of environmental disruption generated by the desalination plant brine discharges and the high salinity in this area. We also observed that the tissues of limpets collected from site H as well as the two other sites, E and W, had undergone molecular damage, confirmed by the high levels of CSP 3-like activity. This damage resulted from chronic exposure to environmental conditions, potentially genotoxic, due to the desalination plant discharges. The present results indicate the adverse impact of brine effluents from desalination plants on marine fauna and suggest the need for a more consistent approach to environmental management of brine discharges.

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Cherry Valley Marketplace Issues Allergy Alert on Undeclared Milk Allergens in “Cherry Valley Vanilla Cupcakes” and “Cherry Valley Chocolate Cupcakes”

Cherry Valley Marketplace, West Hempstead, NY, is recalling its 12-ounce packages of CHERRY VALLEY VANILLA CUPCAKES and CHERRY VALLEY CHOCOLATE CUPCAKES because they may contain undeclared milk allergens. Consumers who are allergic to milk allergens may run the risk of serious or life-threatening allergic reactions if they consume this product.

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Evidence is needed on comparative benefits and harms of pharmacologic products in ideal and real-world settings

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Decision-making about healthcare related tests and diagnostic strategies: A review of methodological and practical challenges

In this first of a series of five articles we provide an overview of how and why healthcare related tests and diagnostic strategies (HCTDS) are currently applied. We also describe how our findings can be integrated with existing frameworks for making decisions that guide the use of HCTDS.

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Controversy and Debate on Clinical Genomics Sequencing - Paper 2: Clinical Genome-Wide Sequencing: Don't Throw Out the Baby With The Bathwater!

Genome-wide (exome or whole genome) sequencing with appropriate genetic counselling should be considered for any patient with a suspected mendelian disease that has not been identified by conventional testing.Clinical genome-wide sequencing provides a powerful and effective meansof identifying specific genetic causes of serious disease and improving clinical care.

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A novel statistical model for analyzing data of a systematic review generates optimal cut-off values for fractional exhaled nitric oxide for asthma diagnosis

Measurement of fractional exhaled nitric oxide (FENO) might substitute bronchial provocation for diagnosing asthma. However, optimal FENO thresholds for diagnosing asthma remain unclear. We re-analyzed data collected for a systematic review investigating the diagnostic accuracy of FENO measurement to exploit all available thresholds under consideration of pre-test probabilities using a newly developed statistical model.

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Decision-making about healthcare related tests and diagnostic strategies: A systematic review shows limitations in most tools designed to assess quality and develop recommendations

To identify and describe critical appraisal tools designed for assessing the quality of evidence (QoE) and/or strength of recommendations (SoR) related to healthcare related tests and diagnostic strategies (HCTDS).

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The Coupling Effect of Rainfall and Reservoir Water Level Decline on the Baijiabao Landslide in the Three Gorges Reservoir Area, China

Rainfall and reservoir level fluctuation are two of the main factors contributing to reservoir landslides. However, in China's Three Gorges Reservoir Area, when the reservoir water level fluctuates significantly, it comes at a time of abundant rainfall, which makes it difficult to distinguish which factor dominates the deformation of the landslide. This study focuses on how rainfall and reservoir water level decline affect the seepage and displacement field of Baijiabao landslide spatially and temporally during drawdown of reservoir water level in the Three Gorges Reservoir Area, thus exploring its movement mechanism. The monitoring data of the landslide in the past 10 years were analyzed, and the correlation between rainfall, reservoir water level decline, and landslide displacement was clarified. By the numerical simulation method, the deformation evolution mechanism of this landslide during drawdown of reservoir water level was revealed, respectively, under three conditions, namely, rainfall, reservoir water level decline, and coupling of the above two conditions. The results showed that the deformation of the Baijiabao landslide was the coupling effect of rainfall and reservoir water level decline, while the latter effect is more pronounced.

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On Singular Solutions to PDEs with Turning Point Involving a Quadratic Nonlinearity

We study a singularly perturbed PDE with quadratic nonlinearity depending on a complex perturbation parameter . The problem involves an irregular singularity in time, as in a recent work of the author and A. Lastra, but possesses also, as a new feature, a turning point at the origin in . We construct a family of sectorial meromorphic solutions obtained as a small perturbation in of a slow curve of the equation in some time scale. We show that the nonsingular parts of these solutions share common formal power series (that generally diverge) in as Gevrey asymptotic expansion of some order depending on data arising both from the turning point and from the irregular singular point of the main problem.

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Tapered, Double-Lead Threads Single Implants Placed in Fresh Extraction Sockets and Healed Sites of the Posterior Jaws: A Multicenter Randomized Controlled Trial with 1 to 3 Years of Follow-Up

Purpose. To evaluate the survival, success, and complication rates of tapered double-lead threads single implants, placed in fresh extraction sockets and healed sites of the posterior jaws. Methods. The enrolled patients were randomly divided into 2 groups: in the test group (TG), all implants were inserted at the time of tooth extraction; in the control group (CG), all implants were placed 3 months after extraction. The implants were followed for a period of 1 to 3 years after loading. The main outcomes were implant survival, complications, and implant-crown success. Results. Ninety-two patients had 97 installed implants (49 in the TG, 48 in the CG). Only two implants failed, in the TG; the survival rates were therefore 95.9% (47/49) and 100% (48/48) for TG and CG, respectively. In the surviving implants, no complications were reported, for an implant-crown success of 100%. Conclusions. Although a significant difference was found in the levels of primary stability between TG and CG, single implants placed in fresh extraction sockets and healed sites of the posterior jaws had similar survival and complication rates. Crestal bone levels and peri-implant bone resorption showed similar values. A longer follow-up period is however required, to confirm these positive outcomes.

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Association between Exposure to Traffic-Related Air Pollution and Prevalence of Allergic Diseases in Children, Seoul, Korea

Although there has been suggestive evidence of the association between TRAP and ADs, findings remained inconsistent possibly due to limited population. We investigated the association between TRAP and ADs in a large population of children with rich spatial coverage and expanded age span in Seoul, Korea. TRAP exposures were estimated by categorized proximity to the nearest major road (≤150, 150–300, 300–500, and >500 m) and density of major roads within 300 meters from children's residences. We estimated the association between two TRAP exposures and three ADs using generalized mixed model after adjusting for individual characteristics. We also investigated whether the association varied by household and regional socioeconomic status. We found associations of atopic eczema with road density [OR = 1.08; 95% CI = 1.01–1.15] and road proximity [1.15, 1.01–1.32; 1.17, 1.03–1.34; and 1.16, 1.01–1.34 for ≤150, 150–300, and 300–500 m, resp., compared to >500 m]. There was no association with asthma and allergic rhinitis. Effect estimates were generally the highest in the low socioeconomic region. Children living in areas surrounded by large and busy roads were likely to be at greater risks for atopic eczema, with increased vulnerability when living in deprived areas.

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Heat Stroke: A Medical Emergency Appearing in New Regions

Heat stroke is an acute, life-threatening emergency characterized clinically by elevated body temperature and central nervous system dysfunction. Early recognition and treatment including aggressive cooling and management of life-threatening systemic complications are essential to reduce morbidity and mortality. This case report describes two Danish patients diagnosed with heat stroke syndrome during a heat wave in the summer of 2014. Both patients were morbidly obese and had several predisposing illnesses. However since heat stroke is a rare condition in areas with temperate climate, they were not diagnosed until several days after admittance; hence treatment with cooling was delayed. Both patients were admitted to the intensive care unit, where they were treated with an external cooling device and received treatment for complications. Both cases ended fatally. As global warming continues, more heat waves will occur in previously cooler regions. Therefore it is important to raise awareness of heat stroke since outcome depends on early recognition and rapid cooling.

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Rare Congenital Aberrant Left Superior Pulmonary Vein Discovered with Central Line Placement in a Patient with Critical Cardiorespiratory Collapse

Background. Partial anomalous pulmonary venous connection is a rare congenital vascular disorder that may be asymptomatic. Left-sided connections with the innominate vein are discovered infrequently and those without an atrial septal defect are extremely rare. Case. A 66-year-old male was found to have an anomalous left pulmonary vein when a central venous catheter was inserted for management of hypoxemia. In addition to the connection with the left innominate vein an echocardiogram revealed no atrial septal defect. Computed tomography arteriography was used to define the anomaly. Conclusion. Left superior vein partial anomalous pulmonary venous connection with the left innominate vein was discovered incidentally on insertion of central venous catheter. The otherwise innocuous anomaly can become a significant variable when treating critical cardiopulmonary collapse.

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Analysis on Time Window of Shared Parking in Hospitals Based on Parking Behaviors

Hospitals are essential components of a city; huge traffic demand is generated and attracted, causing contradiction between parking supply and demand. By sharing parking berths, limited space can serve more demand which is beneficial to alleviating parking problems. Aimed at improving the capacity of shared parking, the paper analyzes four parking groups in typical hospitals, which are medical staff, outpatients, emergency patients, and visiting groups. The parking demand of medical staff is rigid. For outpatients and visiting groups, longer walking distance is acceptable and more attention is paid to parking fee. By contrast, emergency patients can accept shorter walking distance and focus more on convenience due to urgency. Under this circumstance, parking behaviors selection models are established by means of Multinomial Logit Model. On this basis, time value is adopted to calculate the tolerance of alterative parking time. Moreover, this paper explores the variation of time window, under different parking impedance. A case study is conducted and suggests that start and end point of a certain time window can be influenced by external factors.

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Molecular characterization and functional analysis of chalcone synthase from Syringa oblata Lindl. in the flavonoid biosynthetic pathway

Publication date: 30 November 2017
Source:Gene, Volume 635
Author(s): Yu Wang, Ying Dou, Rui Wang, Xuelian Guan, Zenghui Hu, Jian Zheng
The flower color of Syringa oblata Lindl., which is often modulated by the flavonoid content, varies and is an important ornamental feature. Chalcone synthase (CHS) catalyzes the first key step in the flavonoid biosynthetic pathway. However, little is known about the role of S. oblata CHS (SoCHS) in flavonoid biosynthesis in this species.Here, we isolate and analyze the cDNA (SoCHS1) that encodes CHS in S. oblata. We also sought to analyzed the molecular characteristics and function of flavonoid metabolism by SoCHS1.We successfully isolated the CHS-encoding genomic DNA (gDNA) in S. oblata (SoCHS1), and the gene structural analysis indicated it had no intron. The opening reading frame (ORF) sequence of SoCHS1 was 1170bp long and encoded a 389-amino acid polypeptide. Multiple sequence alignment revealed that both the conserved CHS active site residues and CHS signature sequence were in the deduced amino acid sequence of SoCHS1. Crystallographic analysis revealed that the protein structure of SoCHS1 is highly similar to that of FnCHS1 in Freesia hybrida. The quantitative real-time polymerase chain reaction (PCR) performed to detect the SoCHS1 transcript expression levels in flowers, and other tissues revealed the expression was significantly correlated with anthocyanin accumulation during flower development.The ectopic expression results of Nicotiana tabacum showed that SoCHS1 overexpression in transgenic tobacco changed the flower color from pale pink to pink. In conclusion, these results suggest that SoCHS1 plays an essential role in flavonoid biosynthesis in S. oblata, and could be used to modify flavonoid components in other plant species.



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The role of long non-coding RNA PCA3 in epithelial ovarian carcinoma tumorigenesis and progression

Publication date: 30 October 2017
Source:Gene, Volume 633
Author(s): Yao Liu, Zhi-Hong Zong, Xue Guan, Li-li Wang, Yang Zhao
ObjectivesOvarian carcinoma is one of the highest incidence of tumors in women, and the generation, development and prognosis of epithelial ovarian carcinoma (EOC) remains an open field of study. The role of long non-coding RNAs (lncRNAs) in epithelial ovarian carcinoma is an emerging area of research.Materials and methodsLncRNA PCA3 expression was determined in EOC and normal ovarian tissues by RT-PCR. Phenotypes indicative of tumor progression and aggressiveness, including cell proliferation, migration, invasion, and expression of related molecules, were analysed in EOC cell following knockdown of lncRNA PCA3 by transfection with small interfering RNA (siRNA).ResultsExpression of lncRNA PCA3 in epithelial ovarian cancer tissues was higher than in normal ovarian tissue. We discovered that knockdown of lncRNA PCA3 in EOC cells by siRNA transfection significantly suppressed cell proliferation, migration, and invasion. Bioinformatic predictions and dual-luciferase reporter assays indicate that the 3′UTR of PCA3 has potential binding sites for miR-106b-5p. Knockdown of the lncRNA PCA3 by siRNA resulted in up-regulated miR-106b expression. In addition, knockdown of PCA3 also reduced protein expression of Ras homolog gene family member C (RhoC), Bcl/xl, P70 ribosomal S6 kinase (P70S6K), and Matrix metallopeptidase 2 (MMP2), which are regulated by miR-106b.ConclusionsResearch results show that lncRNA PCA3 may coordinate EOC tumorigenesis through disrupting miR-106b regulated gene expression. PCA3 may be a novel and important diagnostic biomarker and a valuable marker for prediction in the clinical care of epithelial ovarian carcinoma.



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Cooperative regulation of Gja1 expression by members of the AP-1 family cJun and cFos in TM3 Leydig and TM4 Sertoli cells

Publication date: 30 November 2017
Source:Gene, Volume 635
Author(s): Firas Ghouili, Luc J. Martin
Within the testis, connexin43 encoded by Gja1 plays an important role in cell-to-cell communication between Leydig cells as well as between Sertoli cells and spermatogonia. In the adult male, Leydig cells are the principal producers of testosterone sustaining spermatogenesis, while Sertoli cells nourish, protect and support the differentiating germ cells. It has been shown previously that members of the AP-1 family regulate Gja1 expression in myometrial cells, suggesting that such regulatory mechanism may also be relevant within the testis. Thus, we performed cotransfections of AP-1 expression plasmids with different mouse Gja1 promoter/luciferase reporter constructs within TM3 Leydig and TM4 Sertoli cells. We showed that a functional cooperation between cJun and cFos activates Gja1 expression and requires an AP-1 DNA regulatory element located between −132 and −26 bp. In addition, such synergy relies on the recruitment of cFos to this region of the mouse Gja1 promoter. Hence, our data indicate that AP-1 members are important for optimal expression of Gja1 within Sertoli and Leydig cells from the testis.



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Isolation and characterization of peroxiredoxin 1 gene of Dunaliella salina

Publication date: 30 November 2017
Source:Gene, Volume 635
Author(s): Fanghua Gong, Jing Wang, Jie Li
Peroxiredoxin 1 (Prdx1) is a ubiquitously expressed protein in eukaryotic cells, and plays an important role in cell proliferation, differentiation, apoptosis, and redox signaling. Although Prdx1 has been better studied in yeasts and humans, only few Prdx1 genes have been cloned in green algae. The microalga Dunaliella salina (D. salina) is a model for the study of a variety of human cilia-related diseases. In this study, a suppression subtractive hybridization cDNA library of D. salina was constructed, and 6 flagellum-associated genes including D. salina Prdx1 (DsPrdx1) were isolated and identified. A 956bp full-length cDNA of DsPrdx1 was cloned using rapid amplification of cDNA end (RACE). The open reading frame (ORF) of this DNA sequence encodes a polypeptide of 201 amino acids with a predicted molecular weight of 22kDa and a theoretical isoelectric point (pI) of 5.27. Sequence comparison showed that Prdx1 is highly evolutionarily conserved from the unicellular green alga D. salina to human. To our knowledge, this is the first reported full-length sequence of Prdx1 in D. salina. Interestingly, the protein expression of DsPrdx1 was obviously increased during flagellar disassembly in D. salina. Additionally, a yeast two-hybrid assay showed interaction between Prdx1 and RNA, and suggested that DsPrdx1 can protect RNA from degradation by RNase. Taken together, DsPrdx1 not only participates in flagellar disassembly, but also protects RNA from degradation.



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Integrative analysis of DNA methylation and mRNA expression during differentiation of umbilical cord blood derived mononuclear cells to endothelial cells

Publication date: 30 November 2017
Source:Gene, Volume 635
Author(s): Yoonjeong Jeong, Yukyung Jun, Jihye Kim, Hyojin Park, Kyu-Sung Choi, Haiying Zhang, Jeong Ae Park, Ja-Young Kwon, Young-Myeong Kim, Sanghyuk Lee, Young-Guen Kwon
Differentiation of umbilical cord blood derived mononuclear cells to endothelial cells is accompanied by massive changes in gene expression. Although methylation and demethylation of DNA likely play crucial roles in regulating gene expression, their interplay during differentiation remains elusive. To address this question, we performed deep sequencing of DNA methylation and mRNA expression to profile global changes in promoter methylation and gene expression during differentiation from mononuclear cells to outgrowing cells. We identified 61 downregulated genes with hypermethylation, including CD74, VAV1, TLR8, and NCF4, as well as 21 upregulated genes with hypomethylation, including ECSCR, MCAM, PGF, and ARHGEF15. Interestingly, gene ontology analysis showed that downregulated genes with hypermethylation were enriched in immune-related functions, and upregulated genes with hypomethylation were enriched in the developmental process and angiogenesis, indicating the important roles of DNA methylation in regulating differentiation. We performed polymerase chain reaction analyses and bisulfite sequencing of representative genes (CD74, VAV1, ECSCR, and MCAM) to verify the negative correlation between DNA methylation and gene expression. Further, inhibition of DNA methyltransferase and demethylase activities using 5′-aza-dc and shRNAs, specific for TET1 and TET2 mRNAs, respectively, revealed that DNA methylation was the main regulator of the reversible expression of functionally important genes. Collectively, our findings implicate DNA methylation as a critical regulator of gene expression during umbilical cord blood derived mononuclear cells to endothelial cell differentiation.



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Silencing of the pentose phosphate pathway genes influences DNA replication in human fibroblasts

Publication date: 30 November 2017
Source:Gene, Volume 635
Author(s): Karolina Fornalewicz, Aneta Wieczorek, Grzegorz Węgrzyn, Robert Łyżeń
Previous reports and our recently published data indicated that some enzymes of glycolysis and the tricarboxylic acid cycle can affect the genome replication process by changing either the efficiency or timing of DNA synthesis in human normal cells. Both these pathways are connected with the pentose phosphate pathway (PPP pathway). The PPP pathway supports cell growth by generating energy and precursors for nucleotides and amino acids. Therefore, we asked if silencing of genes coding for enzymes involved in the pentose phosphate pathway may also affect the control of DNA replication in human fibroblasts. Particular genes coding for PPP pathway enzymes were partially silenced with specific siRNAs. Such cells remained viable. We found that silencing of the H6PD, PRPS1, RPE genes caused less efficient enterance to the S phase and decrease in efficiency of DNA synthesis. On the other hand, in cells treated with siRNA against G6PD, RBKS and TALDO genes, the fraction of cells entering the S phase was increased. However, only in the case of G6PD and TALDO, the ratio of BrdU incorporation to DNA was significantly changed. The presented results together with our previously published studies illustrate the complexity of the influence of genes coding for central carbon metabolism on the control of DNA replication in human fibroblasts, and indicate which of them are especially important in this process.



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When figures and data contradict text: MiR346 is apparently reduced in breast cancer tissue, contrary to claims by a paper's author

Publication date: 30 November 2017
Source:Gene, Volume 635
Author(s): Debomoy K. Lahiri, Bryan Maloney, Kumar Sambamurti
A recent article in Gene highlighted potential function of miR-346 in human breast cancer (Yang et al., 2017). We request an explanation or correction of the report. In its current state, the text will certainly create confusion in the field and lead to incorrect assumptions. The authors made several critical errors. The abstract stated "we found that the expression of miR-346 was higher in breast cancer tissues than in their paired corresponding non-cancerous tissues" and the main text and legend for Fig. 1A stated "miR-346 expression was significantly higher in breast cancer tissues than in their paired corresponding non-cancerous tissues (Fig. 1A, Yang et al., 2017)" and "miR-346 was upregulated in breast cancer tissues and cell lines. (A)", respectively. It was also stated that "SRCIN1 expression levels were significantly down-regulated in breast cancer compared to the adjacent normal tissues (Fig. 5B, Yang et al., 2017)". The problem with these statements is that they contradict the actual data presented in the paper! This misrepresentation of the effects of miR-346 in breast cancer could prove harmful by sidetracking future research. Further, clinical trials may be incorrectly directed towards lowering miR-346 without a complete and fair assessment of the internal contradictions in the data. Inaccurately-presented data impede progress of biomedical research, deplete scientific resources and compromise public trust.



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Editorial Board

Publication date: 30 October 2017
Source:Gene, Volume 633





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Identification of apoptosis-related genes Bcl2 and Bax from yellow catfish Pelteobagrus fulvidraco and their transcriptional responses to waterborne and dietborne zinc exposure

Publication date: 30 October 2017
Source:Gene, Volume 633
Author(s): Dan-Dan Li, Zhi Luo, Guang-Hui Chen, Yu-Feng Song, Chuan-Chuan Wei, Ya-Xiong Pan
Apoptosis plays a key role in the physiology of multicellular organisms, and has been well studied in mammals, but not in teleosts. Zinc (Zn) has been shown to be an important regulator of apoptosis and apoptosis involves in the regulation of lipid metabolism. Moreover, our recent study indicated that waterborne and dietborne Zn exposure differently influenced lipid metabolism in Pelteobagrus fulvidraco, but further mechanism remained unknown. The hypothesis of the present study is that apoptosis mediated the Zn-induced changes of lipid metabolism of P. fulvidraco subjected to different exposure pathways. To this end, we cloned full-length cDNA sequences of Bcl2 and three Bax subtypes involved in apoptosis in P. fulvidraco, explored their mRNA expressions in responses to different Zn exposure pathways. Bcl2 and three Bax subtypes shared similar domain structure as typical pro- and anti-apoptotic Bcl2 family members. Their mRNAs were widely expressed among various tissues, but at variable levels. Waterborne Zn exposure down-regulated mRNA levels of Baxg and ratios of Baxa/Bcl2, and Baxg/Bcl2, but showed no significant effects on mRNA abundances of Bcl2, Baxa and Baxb, and the ratio of Baxb/Bcl2. In contrast, dietborne Zn exposure up-regulated mRNA levels of Bcl2, Baxa, Baxb and Baxg, but reduced the ratios of Baxa/Bcl2, Baxb/Bcl2, and Baxg/Bcl2. Considering their important roles of these genes in apoptosis induced by Zn, apoptosis may mediate the Zn-induced changes of hepatic lipid metabolism of Pelteobagrus fulvidraco under different Zn exposure pathways. For the first time, we characterized the full-length cDNA sequences of Bcl2 and three Bax subtypes, determined their expression profiles and transcriptional responses to different Zn exposure pathways, which would contribute to our understanding of the molecular basis of apoptosis, and also provide new insights into physiological responses to different Zn exposure pathways.



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