Adenosine monophosphate-activated protein kinase (AMPK) plays a critical role in the regulation of energy metabolism and has been targeted for drug development of therapeutic intervention in Type II diabetes and related diseases. Recently, there has been renewed interest in the development of direct β1-selective AMPK activators to treat patients with diabetic nephropathy. To investigate the details of AMPK domain structure, sequence alignment and structural comparison were used to identify the key amino acids involved in the interaction with activators and the structure difference between β1 and β2 subunits. Additionally, a series of potential β1-selective AMPK activators were identified by virtual screening using molecular docking. The retrieved hits were filtered on the basis of Lipinski's rule of five and drug-likeness. Finally, 12 novel compounds with diverse scaffolds were obtained as potential starting points for the design of direct β1-selective AMPK activators.
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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
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- IJMS, Vol. 18, Pages 1408: Identification of Direc...
- IJMS, Vol. 18, Pages 1404: Histone Lysine Methylat...
- IJMS, Vol. 18, Pages 1402: Capsaicin-Sensitive Sen...
- IJMS, Vol. 18, Pages 1405: Estrogen Promotes Hepat...
- IJERPH, Vol. 14, Pages 713: Farmers’ Risk Preferen...
- IJERPH, Vol. 14, Pages 711: Covariates of Identifi...
- IJERPH, Vol. 14, Pages 708: In Silico Prediction f...
- IJERPH, Vol. 14, Pages 712: Early Onset of Type 1 ...
- IJERPH, Vol. 14, Pages 706: Green Mind Theory: How...
- IJERPH, Vol. 14, Pages 715: Sustainable Use of Pes...
- IJERPH, Vol. 14, Pages 705: Risk Analysis of a Fue...
- Resting heart rate, guilt, and sympathy: A develop...
- Effects of prior mental effort on picture processi...
- Sympathetic and parasympathetic cardiac responses ...
- Piezoelectric versus conventional techniques for o...
- Surrogate mother
- Letter to Editors: Detection of endolymphatic hydr...
- Solitary fibrous tumour of the pleura presenting a...
- Ubiquitous and Ambient Intelligence Assisted Learn...
- Can syncope cause convulsive seizures in adults?
- The use of handheld nasal spirometry to predict th...
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Παρασκευή 30 Ιουνίου 2017
IJMS, Vol. 18, Pages 1408: Identification of Direct Activator of Adenosine Monophosphate-Activated Protein Kinase (AMPK) by Structure-Based Virtual Screening and Molecular Docking Approach
IJMS, Vol. 18, Pages 1404: Histone Lysine Methylation and Neurodevelopmental Disorders
Methylation of several lysine residues of histones is a crucial mechanism for relatively long-term regulation of genomic activity. Recent molecular biological studies have demonstrated that the function of histone methylation is more diverse and complex than previously thought. Moreover, studies using newly available genomics techniques, such as exome sequencing, have identified an increasing number of histone lysine methylation-related genes as intellectual disability-associated genes, which highlights the importance of accurate control of histone methylation during neurogenesis. However, given the functional diversity and complexity of histone methylation within the cell, the study of the molecular basis of histone methylation-related neurodevelopmental disorders is currently still in its infancy. Here, we review the latest studies that revealed the pathological implications of alterations in histone methylation status in the context of various neurodevelopmental disorders and propose possible therapeutic application of epigenetic compounds regulating histone methylation status for the treatment of these diseases.
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IJMS, Vol. 18, Pages 1402: Capsaicin-Sensitive Sensory Nerves Are Necessary for the Protective Effect of Ghrelin in Cerulein-Induced Acute Pancreatitis in Rats
Ghrelin was shown to exhibit protective and therapeutic effect in the gut. Aim of the study was to investigate the role of sensory nerves (SN) in the protective effect of ghrelin in acute pancreatitis (AP). Studies were performed on male Wistar rats or isolated pancreatic acinar cells. After capsaicin deactivation of sensory nerves (CDSN) or treatment with saline, rats were pretreated intraperitoneally with ghrelin or saline. In those rats, AP was induced by cerulein or pancreases were used for isolation of pancreatic acinar cells. Pancreatic acinar cells were incubated in cerulein-free or cerulein containing solution. In rats with intact SN, pretreatment with ghrelin led to a reversal of the cerulein-induced increase in pancreatic weight, plasma activity of lipase and plasma concentration of tumor necrosis factor-α (TNF-α). These effects were associated with an increase in plasma interleukin-4 concentration and reduction in histological signs of pancreatic damage. CDSN tended to increase the severity of AP and abolished the protective effect of ghrelin. Exposure of pancreatic acinar cells to cerulein led to increase in cellular expression of mRNA for TNF-α and cellular synthesis of this cytokine. Pretreatment with ghrelin reduced this alteration, but this effect was only observed in acinar cells obtained from rats with intact SN. Moreover, CDSN inhibited the cerulein- and ghrelin-induced increase in gene expression and synthesis of heat shock protein 70 (HSP70) in those cells. Ghrelin exhibits the protective effect in cerulein-induced AP on the organ and pancreatic acinar cell level. Sensory nerves ablation abolishes this effect.
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IJMS, Vol. 18, Pages 1405: Estrogen Promotes Hepatic Synthesis of Long-Chain Polyunsaturated Fatty Acids by Regulating ELOVL5 at Post-Transcriptional Level in Laying Hens
The very long chain fatty acid elongase (ELOVL) plays an important role in the synthesis of long-chain polyunsaturated fatty acids (LCPUFA). Previous studies suggest that chicken could be an alternate source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In this study, we detected that ELOVL5, which plays a key role in the biosynthesis of omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFA), was highly expressed in the liver of laying hens and increased rapidly after sexual maturity. Bioinformatic analysis revealed ELOVL fatty acid elongase 5 (ELOVL5) gene as a putative target of miR-218-5p, miR-19a-3p, miR-19b-3p, miR-30a-5p, miR-30b-5p, and miR-30e-5p. We demonstrated estrogen downregulated microRNA (miRNA), and that ELOVL5 is a direct target of miR-218-5p, which was located in intron 14 of the Slit guidance ligand 2 (SLIT2) gene and co-expressed with the host gene. Overall, estrogen enhanced hepatic synthesis of LCPUFA by functioning as a negative regulator of miRNA thereby augmenting the expression of these miRNA target genes, especially ELOVL5, which plays a key role in the biosynthesis of n-3 and n-6 LCPUFA. This study provides a novel model for the use of estrogen in the poultry industry as an inducer of ELOVL5 expression to enhance hepatic n-3 and n-6 LCPUFA synthesis at the post-transcriptional level.
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IJERPH, Vol. 14, Pages 713: Farmers’ Risk Preferences in Rural China: Measurements and Determinants
This study measures farmers' risk attitudes in rural China using a survey instrument and a complementary experiment conducted in the field with the same sample of subjects. Using a question asking people about their willingness to take risks "in general", we found that the average response of our sample is slightly risk averse. Farmers' exogenous factors (age, gender, and height) and self-reported happiness have a significant impact on farmers' willingness to take risks. The experiment results show that approximately 44% of farmers in the study area are risk averse. We compare farmers' self-reported measures of risk preferences derived from the survey instrument to preferences elicited through the experimental task. Results show that answers to the general risk attitude question in the survey can predict farmers' behaviors in the experiment to a statistically significant degree. This paper can contribute to the empirical literature on comparing local farmers' risk attitudes across different risk preference measurement methods in the developing world.
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IJERPH, Vol. 14, Pages 711: Covariates of Identified Stress and Depression among Seasonal Farmworkers
Many noted difficulties of farmworker life result in increased risk for stress and depression. To date, limited research has focused primarily on seasonal farmworkers; much of the prior research examines migrant farmworkers or both groups collectively. This study aims to: (1) describe levels of stress and depression among a sample of seasonal farmworkers; and (2) identify if covariates (age, gender, marital status, education level, years of residency, problems obtaining healthcare due to documentation, language barriers, transportation, costs, medical insurance, and stress level) are significant predictors of depressive symptoms. Survey data were collected from 150 Latino seasonal farmworkers. A hierarchical binary logistic regression was conducted to identify significant covariates. The results indicated that the only statistically significant covariates were health insurance coverage (p = 0.025) and stress (p = 0.008). Those farmworkers without health insurance were 1.8 times more likely than those with health insurance to possess depressive symptoms, while those demonstrating higher stress levels were over 7 times more likely to demonstrate symptoms of depression. The implications of the results are discussed in the manuscript.
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IJERPH, Vol. 14, Pages 708: In Silico Prediction for Intestinal Absorption and Brain Penetration of Chemical Pesticides in Humans
Intestinal absorption and brain permeation constitute key parameters of toxicokinetics for pesticides, conditioning their toxicity, including neurotoxicity. However, they remain poorly characterized in humans. The present study was therefore designed to evaluate human intestine and brain permeation for a large set of pesticides (n = 338) belonging to various chemical classes, using an in silico graphical BOILED-Egg/SwissADME online method based on lipophilicity and polarity that was initially developed for drugs. A high percentage of the pesticides (81.4%) was predicted to exhibit high intestinal absorption, with a high accuracy (96%), whereas a lower, but substantial, percentage (38.5%) displayed brain permeation. Among the pesticide classes, organochlorines (n = 30) constitute the class with the lowest percentage of intestine-permeant members (40%), whereas that of the organophosphorus compounds (n = 99) has the lowest percentage of brain-permeant chemicals (9%). The predictions of the permeations for the pesticides were additionally shown to be significantly associated with various molecular descriptors well-known to discriminate between permeant and non-permeant drugs. Overall, our in silico data suggest that human exposure to pesticides through the oral way is likely to result in an intake of these dietary contaminants for most of them and brain permeation for some of them, thus supporting the idea that they have toxic effects on human health, including neurotoxic effects.
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IJERPH, Vol. 14, Pages 712: Early Onset of Type 1 Diabetes and Educational Field at Upper Secondary and University Level: Is Own Experience an Asset for a Health Care Career?
Ill health in early life has a significant negative impact on school grades, grade repetition, educational level, and labor market outcomes. However, less is known about qualitative socio-economic consequences of a health shock in childhood or adolescence. We investigate the relationship between onset of type 1 diabetes up to age 15 and the probability of choosing and completing a health-oriented path at upper secondary and university level of education. We analyze the Swedish Childhood Diabetes Register, the National Educational Register, and other population registers in Sweden for 2756 people with type 1 diabetes and 10,020 matched population controls. Educational decisions are modeled as unsorted series of binary choices to assess the choice of educational field as a potential mechanism linking early life health to adult outcomes. The analyses reject the hypothesis of no systematic differences in choice of educational field between people with and without type 1 diabetes at both levels. The results are robust to selection on ability proxies and across sensitivity analysis. We conclude that the observed pro health-oriented educational choices among people with type 1 diabetes in our data are consistent with disease onset in childhood and adolescence having qualitative impact on life-course choices.
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IJERPH, Vol. 14, Pages 706: Green Mind Theory: How Brain-Body-Behaviour Links into Natural and Social Environments for Healthy Habits
We propose a Green Mind Theory (GMT) to link the human mind with the brain and body, and connect the body into natural and social environments. The processes are reciprocal: environments shape bodies, brains, and minds; minds change body behaviours that shape the external environment. GMT offers routes to improved individual well-being whilst building towards greener economies. It builds upon research on green exercise and nature-based therapies, and draws on understanding derived from neuroscience and brain plasticity, spiritual and wisdom traditions, the lifeways of original cultures, and material consumption behaviours. We set out a simple metaphor for brain function: a bottom brain stem that is fast-acting, involuntary, impulsive, and the driver of fight and flight behaviours; a top brain cortex that is slower, voluntary, the centre for learning, and the driver of rest and digest. The bottom brain reacts before thought and directs the sympathetic nervous system. The top brain is calming, directing the parasympathetic nervous system. Here, we call the top brain blue and the bottom brain red; too much red brain is bad for health. In modern high-consumption economies, life has often come to be lived on red alert. An over-active red mode impacts the gastrointestinal, immune, cardiovascular, and endocrine systems. We develop our knowledge of nature-based interventions, and suggest a framework for the blue brain-red brain-green mind. We show how activities involving immersive-attention quieten internal chatter, how habits affect behaviours across the lifecourse, how long habits take to be formed and hard-wired into daily practice, the role of place making, and finally how green minds could foster prosocial and greener economies. We conclude with observations on twelve research priorities and health interventions, and ten calls to action.
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IJERPH, Vol. 14, Pages 715: Sustainable Use of Pesticide Applications in Citrus: A Support Tool for Volume Rate Adjustment
Rational application of pesticides by properly adjusting the amount of product to the actual needs and specific conditions for application is a key factor for sustainable plant protection. However, current plant protection product (PPP) labels registered for citrus in EU are usually expressed as concentration (%; rate/hl) and/or as the maximum dose of product per unit of ground surface, without taking into account those conditions. In this work, the fundamentals of a support tool, called CitrusVol, developed to recommend mix volume rates in PPP applications in citrus orchards using airblast sprayers, are presented. This tool takes into consideration crop characteristics (geometry, leaf area density), pests, and product and application efficiency, and it is based on scientific data obtained previously regarding the minimum deposit required to achieve maximum efficacy, efficiency of airblast sprayers in citrus orchards, and characterization of the crop. The use of this tool in several commercial orchards allowed a reduction of the volume rate and the PPPs used in comparison with the commonly used by farmers of between 11% and 74%, with an average of 31%, without affecting the efficacy. CitrusVol is freely available on a website and in an app for smartphones.
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IJERPH, Vol. 14, Pages 705: Risk Analysis of a Fuel Storage Terminal Using HAZOP and FTA
The size and complexity of industrial chemical plants, together with the nature of the products handled, means that an analysis and control of the risks involved is required. This paper presents a methodology for risk analysis in chemical and allied industries that is based on a combination of HAZard and OPerability analysis (HAZOP) and a quantitative analysis of the most relevant risks through the development of fault trees, fault tree analysis (FTA). Results from FTA allow prioritizing the preventive and corrective measures to minimize the probability of failure. An analysis of a case study is performed; it consists in the terminal for unloading chemical and petroleum products, and the fuel storage facilities of two companies, in the port of Valencia (Spain). HAZOP analysis shows that loading and unloading areas are the most sensitive areas of the plant and where the most significant danger is a fuel spill. FTA analysis indicates that the most likely event is a fuel spill in tank truck loading area. A sensitivity analysis from the FTA results show the importance of the human factor in all sequences of the possible accidents, so it should be mandatory to improve the training of the staff of the plants.
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Resting heart rate, guilt, and sympathy: A developmental psychophysiological study of physical aggression
Abstract
Although low resting heart rate has been linked to frequent aggressive conduct in childhood, little is known about the interaction of this biological risk with social emotions that protect against aggression across development. With a sample of 5-, 8-, and 12-year-olds (N = 110), we tested whether the negative link between resting heart rate and physical aggression was offset by high guilt and sympathy. Caregivers reported their children's physical aggression and sympathy. Children's electrocardiogram data were collected while they viewed a nondescript video, after which they reported their guilt—or lack thereof—in response to vignettes depicting social transgressions. Lower resting heart rate was significantly associated with higher physical aggression in 5-year-olds who reported low—but not medium and high—levels of guilt, and in 8-year-olds with low—but not medium and high—ratings of sympathy. Neither guilt nor sympathy moderated the resting heart rate–physical aggression link in 12-year-olds. We discuss how social emotions may help children with low resting heart rates navigate social conflicts and avoid aggressive physical confrontations.
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Effects of prior mental effort on picture processing: An ERP investigation
Abstract
The current study examined the aftereffects of mental effort on the processing of picture stimuli using neural measures. Ninety-seven healthy young adults were randomly assigned to exercise more versus less mental effort on a writing task. Then participants viewed positive, negative, and neutral affective images while P1, N1, P2, N2, P3, and late positive potential (LPP) magnitudes to the images were assessed. We found that performing the more (versus less) effortful writing task caused more negative N2 amplitudes to all images. In addition, and consistent with past research, emotional (versus neutral) images elicited more positive amplitudes on the N2, P3, and LPP components. Thus, prior mental effort appeared to reduce early attentional engagement with visual stimuli but did not diminish later attention modulation by emotional content. These findings suggest novel implications for understanding the behavioral aftereffects of mental effort and self-control.
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Sympathetic and parasympathetic cardiac responses to phobia-relevant and disgust-specific emotion provocation in blood-injection-injury phobia with and without fainting history
Abstract
The autonomic regulation in blood-injection-injury (BII) phobia has received particular attention due to the unique link between fear and fainting in this anxiety disorder. However, systematic exploration of sympathetic and parasympathetic cardiac activity during exposure to phobia-relevant emotional stimuli has remained rare and inconclusive, including with regard to disgust, a frequent response to BII stimuli. Existing studies using respiratory sinus arrhythmia (RSA) as a noninvasive index of parasympathetic cardiac activity also have not accounted sufficiently for effects of respiration. We compared 60 participants with BII phobia (27 with and 33 without history of loss of consciousness) and 20 healthy controls during emotion induction with films, including a disgust and a BII-relevant surgery film. Cardiorespiratory activity was measured continuously, with RSA (controlled for respiration) and T-wave amplitude (TWA; as a noninvasive index of sympathetic cardiac activity) extracted. Significant increases in RSA during the surgery film were observed for participants with a history of loss of consciousness compared to others, but controlling for respiration eliminated these differences. Sympathetic effects with heart rate accelerations, which were most pronounced for the disgust film, did not differentiate groups. However, substantial increases in RSA and TWA, suggesting parasympathetic excitation and sympathetic withdrawal, were observed in five participants that became presyncopal during the surgery film. Thus, parasympathetic excitation and sympathetic withdrawal appear to be cardinal autonomic features in BII phobia, but larger studies of participants reaching presyncopal states in BII-relevant stimulus exposure are needed to consolidate these findings.
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Piezoelectric versus conventional techniques for orthognathic surgery: Systematic review and meta-analysis
The purpose of this study was to perform a systematic review and meta-analysis of complications after orthognathic surgery comparing piezosurgery with conventional osteotomy.
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Surrogate mother
Surrogate mother: Also known as surrogate. A woman who agrees to become pregnant and carry a child for another individual or couple, who will become the child's legal parents. In some situations and locations a surrogate mother may be paid for her services. In traditional surrogacy, the woman becomes pregnant using her own eggs and is the biological mother of the child. The term is sometimes used to refer to a woman who carries a biologically unrelated child for another couple that was conceived through in-vitro fertilization (IVF), but the term gestational carrier or gestational surrogate is more accurate in this situation.
MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
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Letter to Editors: Detection of endolymphatic hydrops using traditional MR imaging sequences
We would like to comment on the manuscript entitled "Detection of endolymphatic hydrops using traditional MR imaging sequences." by Keller et al. [1]. It is of great clinical value if non-contrast MR imaging can be used to differentiate the endo- and perilymph space as the authors have stated. We read this article with great interest and thank the authors for citing our six papers. However, there are some critical points that need to be clarified in this paper.
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Solitary fibrous tumour of the pleura presenting as a giant intrathoracic mass
Solitary fibrous tumours (SFTs) are relatively rare neoplasms thought to originate from the submesothelial connective tissue. SFTs have been described in a variety of sites, including the pleura, orbit, lower respiratory tract, peritoneal cavity and heart. These neoplasms are usually benign, though locally aggressive, and metastatic behaviour has been observed in some cases. We describe a case of a 61-year-old man presenting with weight loss, poor appetite, malaise, worsening dyspnoea on exertion and lower extremity oedema, who was found to have a gigantic—21x21 cm—tumour occupying the entire right hemithorax causing compression and displacement of the mediastinum and liver. Transthoracic CT-guided biopsy revealed SFT of the pleura. The patient underwent preoperative angiography and embolisation of the tumour followed by successful surgical resection via thoracotomy.
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Ubiquitous and Ambient Intelligence Assisted Learning Environment Infrastructures Development - a review
Abstract
Ubiquitous Learning Environment (ULE) has been becoming a mobile and sensor based technology equipped environment that suits the modern world education discipline requirements for the past few years. Ambient Intelligence (AmI) makes much smarter the ULE by the support of optimization and intelligent techniques. Various efforts have been so far made as contributions to develop such smart environments. Hence a study is required to know the various smartness levels incorporated in those contributions. In this regard, first, a review on infrastructural developments for ubiquitous learning is reported in this article. Next, this report addresses various open issues, problems & requirements, technology challenges and potential improvements within the scope of Ubiquitous Learning Environment and Ambient Intelligence Assisted Learning Environment (AmIALE). It then also recommends an Internet-of-Things (IoT) enabled Ubiquitous Learning Environment for offering still smarter levels like energy efficiency, connectivity, special needs, Multi-modal Human Computer Interaction, Self-Optimization and Self-Discovery in an effective manner. We strongly believe that this work helps the researchers to start thinking in a different dimension to find solutions for various other current issues.
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Can syncope cause convulsive seizures in adults?
Abstract
Purpose
Convulsive epileptic seizures triggered by transient cerebral hypoperfusion 'reflex anoxic seizures' are well-described in children but are not commonly recognized in adults.
Methods
We report a case series of 12 adults who presented acutely after generalized tonic–clonic seizures with a clear syncopal phase before the convulsion. We describe the aetiology, semiology and natural history of these events.
Results
Four patients (33.3%) had relevant risk factors for development of seizures/active epilepsy. Five patients (41.7%) had recurrent events prior to initial review by an epileptologist, but when anti-syncope measures were instituted there were no seizure recurrences over a median follow-up period of 34.5 (interquartile range 29.3–41.8) months.
Conclusions
Syncope may be an under-recognized trigger for convulsive acute symptomatic seizures. Avoidance of syncope may be more effective than anti-seizure medications in preventing reflex anoxic seizures.
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The use of handheld nasal spirometry to predict the presence of obstructive sleep apnea
Abstract
Objective
Nasal obstruction and oral breathing may play an important role in the pathophysiology of obstructive sleep apnea (OSA). This study aims to better understand the link between oral breathing, nasal obstruction, and the spectrum of sleep-disordered breathing.
Study Design
Prospective study.
Methods and materials
Prospective study of patients who presented to the Otolaryngology clinic and underwent polysomnogram (PSG) from 2015 to 2016. Patients were divided into two groups based on the severity of their OSA as defined by PSG results. Both apnea-hypopnea index (AHI) and supine and REM AHI (SUP-REMe AHI), a parameter that takes into account both sleep position and sleep stage, were recorded. The primary outcome was awake nasal-oral forced expiratory volume in 1-s (FEV1) ratio as measured by handheld spirometry.
Results
A total of 21 patients were included in the study. We found that nasal-oral FEV1 ratio was significantly different between patients with minimal and substantial OSA as stratified by SUP-REMe AHI, while not significant when stratified by AHI.
Conclusion
Patients with substantial OSA as determined by SUP-REMe AHI are more likely to have decreased awake nasal airflow as measured by nasal-oral FEV1. SUP-REMe AHI may represent an improved metric of OSA severity by taking into account sleep position and sleep stage. Handheld spirometers have the potential to become an important office tool by allowing for easy and reliable measurement of nasal airflow.
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Informations médicales avant réalisation d’une manométrie anorectale
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Cryptic and pseudo-cryptic diversity in the world’s most common bark beetle— Hypothenemus eruditus
Abstract
Hypothenemus eruditus is regarded as the world's most common bark beetle, collected from numerous host plants on all forested continents. Previous taxonomic treatments remark that the species is morphologically variable and difficult to identify, but to date, no study has analyzed molecular data to investigate possible cryptic or seemingly cryptic (pseudo-cryptic) diversity in this species. We sequenced 216 specimens matching or closely resembling the currently accepted description of H. eruditus for a mitochondrial (COI) and a nuclear marker (28S), and scored six morphological characters. We also compared the morphology of H. eruditus syntypes and type material of 26 synonymized species with the sequenced material. The sequenced material grouped in 21 operational taxonomic units (OTUs) supported by both molecular and morphological data, 17 of which were part of an apparent H. eruditus species complex. Another nine cryptic OTUs, distinguishable only by molecular data, were also included in the complex. Only one of the OTUs revealed a morphological match with the H. eruditus syntypes. The 26 synonymized species were split into 14 tentative morphs, 11 of which did not match the H. eruditus syntypes. We argue that many of our sequenced OTUs deserve species status, and that many species synonymized under H. eruditus should be resurrected.
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Phonological awareness in German-speaking preschool children with cochlear implants – 3 case examples
The aim was to explore PA skills German-speaking preschool children with cochlea implants (CIs) and how these skills may be related to their speech and language skills.
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Phonological awareness in German-speaking preschool children with cochlear implants – 3 case examples
The aim was to explore PA skills German-speaking preschool children with cochlea implants (CIs) and how these skills may be related to their speech and language skills.
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Crosslinking of Dicyclotyrosine by the Cytochrome P450 Enzyme CYP121 from Mycobacterium tuberculosis Proceeds through a Catalytic Shunt Pathway [Molecular Bases of Disease]
CYP121, the P450 enzyme in Mycobacterium tuberculosis that catalyzes a single intramolecular C-C crosslinking reaction in the biosynthesis of mycocyclosin, is crucial for the viability of this pathogen. This C-C coupling reaction represents an expansion of the activities carried out by P450 enzymes distinct from oxygen insertion. While the traditional mechanism for P450 enzymes has been well studied, it is unclear whether CYP121 follows the general P450 mechanism or uses a different catalytic strategy for generating an iron-bound oxidant. To gain mechanistic insight into the CYP121-catalyzed reaction, we tested the peroxide shunt pathway by using rapid kinetic techniques to monitor the enzyme activity with its substrate dicyclotyrosine (cYY) and observed the formation of the crosslinked product mycocyclosin by LC-MS. In stopped‐flow experiments, we observed that cYY binding to CYP121 proceeds in a two‐step process, and EPR spectroscopy indicates that the binding induces active site reorganization and uniformity. Using rapid freeze-quenching EPR, we observed formation of a high-spin intermediate upon addition of peracetic acid to the enzyme-substrate complex. This intermediate exhibits a high-spin (S = 5/2) signal with g values of 2.00, 5.77, and 6.87. Likewise, iodosylbenzene could also produce mycocyclosin, implicating compound I as the initial oxidizing species. Moreover, we also demonstrated that CYP121 performs a standard peroxidase-type of reaction by observing substrate-based radicals. On the basis of these results, plausible free radical-based mechanisms for the C-C bond coupling reaction are proposed.
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A haplotype variant of the human chromogranin A gene (CHGA) promoter increases CHGA expression and the risk for cardiometabolic disorders [Gene Regulation]
The acidic glycoprotein chromogranin A (CHGA) is co-stored/co-secreted with catecholamines and crucial for secretory vesicles biogenesis in neuronal/neuroendocrine cells. CHGA is dysregulated in several cardiovascular diseases, but the underlying mechanisms are not well established. Here, we sought to identify common polymorphisms in the CHGA promoter and to explore the mechanistic basis of their plausible contribution to regulating CHGA protein levels in circulation. Resequencing of the CHGA promoter in an Indian population (n=769) yielded nine SNPs: G-1106A, A-1018T, T-1014C, T-988G, G-513A, G-462A, T-415C, C-89A and C-57T. Linkage disequilibrium (LD) analysis indicated strong LD among SNPs at the -1106, -1014, -988 and -89 bp positions and between the -1018 and -57 bp positions. Haplotype analysis predicted five major promoter haplotypes that displayed differential promoter activities in neuronal cells; specifically, haplotype 2 (containing variant T alleles at -1018 and -57 bp) exhibited the highest promoter activity. Systematic computational and experimental analyses revealed that transcription factor c-Rel has a role in activating the CHGA promoter haplotype 2 under basal and pathophysiological conditions (viz. inflammation and hypoxia). Consistent with the higher in vitro CHGA promoter activity of haplotype 2, individuals carrying this haplotype had higher plasma CHGA levels, plasma glucose levels, diastolic blood pressure, and body mass index. In conclusion, these results suggest a functional role of the CHGA promoter haplotype 2 (occurring in a large proportion of the World population) in enhancing CHGA expression in haplotype 2 carriers who may be at higher risk for cardiovascular/metabolic disorders.
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Neuropilin-1 promotes Hedgehog signaling through a novel cytoplasmic motif [Signal Transduction]
Hedgehog (HH) signaling critically regulates embryonic and postnatal development as well as adult tissue homeostasis, and its perturbation can lead to developmental disorders, birth defects, and cancers. Neuropilins (NRPs), which have well-defined roles in Semaphorin and VEGF signaling, positively regulate HH pathway function, although their mechanism of action in HH signaling remains unclear. Here, using luciferase-based reporter assays, we provide evidence that NRP1 regulates HH signaling, specifically at the level of GLI transcriptional activator function. Moreover, we show that NRP1 localization to the primary cilium, a key platform for HH signal transduction, does not correlate with HH signal promotion. Rather, a structure-function analysis suggested that the NRP1 cytoplasmic and transmembrane domains are necessary and sufficient to regulate HH pathway activity. Furthermore, we identify a previously uncharacterized, 12-amino-acid region within the NRP1 cytoplasmic domain that mediates HH signal promotion. Overall, our results provide mechanistic insight into NRP1 function within and potentially beyond the HH signaling pathway. These insights have implications for the development of novel modulators of HH-driven developmental disorders and diseases.
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The gluconate shunt is an alternative route for directing glucose into the pentose phosphate pathway in fission yeast [Gene Regulation]
Glycolysis and the pentose phosphate pathway both play a central role in the degradation of glucose in all domains of life. Another metabolic route that can facilitate glucose breakdown is the gluconate shunt. In this shunt glucose dehydrogenase and gluconate kinase catalyze the two-step conversion of glucose into the pentose phosphate pathway intermediate 6-phosphogluconate. Despite the presence of these enzymes in many organisms, their only established role is in the production of 6-phosphogluconate for the Entner-Doudoroff pathway. In this report we performed metabolic profiling on a strain of Schizosaccharomyces pombe lacking the zinc-responsive transcriptional repressor Loz1 with the goal of identifying metabolic pathways that were altered by cellular zinc status. This profiling revealed that loz1Δ cells accumulate higher levels of gluconate. We show that the altered gluconate levels in loz1Δ cells result from increased expression of gcd1. By analyzing the activity of recombinant Gcd1 in vitro and by measuring gluconate levels in strains lacking enzymes of the gluconate shunt we demonstrate that Gcd1 encodes a novel NADP+-dependent glucose dehydrogenase that acts in a pathway with the Idn1 gluconate kinase. We also find that cells lacking gcd1 and zwf1, which encodes the first enzyme in the pentose phosphate pathway, have a more severe growth phenotype than cells lacking zwf1. We propose that in S. pombe Gcd1 and Idn1 act together to shunt glucose into the pentose phosphate pathway, creating an alternative route for directing glucose into the pentose phosphate pathway that bypasses hexokinase and the rate-limiting enzyme glucose 6-phosphate dehydrogenase.
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Implementing and Sustaining Team-Based Telecare for Bipolar Disorder: Lessons Learned from a Model-Guided, Mixed Methods Analysis
Telemedicine and e-Health , Vol. 0, No. 0.
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Cold atmospheric plasma restores tamoxifen sensitivity in resistant MCF-7 breast cancer cell
Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110
Author(s): Seungyeon Lee, Hyunkyung Lee, Dawoon Jeong, Juyeon Ham, Sungbin Park, Eun Ha Choi, Sun Jung Kim
Cancer recurrence, which is frequently accompanied by chemotherapy, has been a challenge in cancer treatment. This study was carried out to examine the potential applications of the reactive oxygen species (ROS)-producing cold atmospheric plasma (CAP) to overcome the cancer cells' drug resistance, which has been emerging as an alternative therapeutic tool for cancer. For this, we developed a tamoxifen (Tam)-resistant MCF-7 (MCF-7/TamR) breast cancer cell model and examined the effect of CAP on the recovery of Tam sensitivity at the cellular and molecular level. The ROS level was increased 1.9-fold in CAP-treated MCF-7/TamR cells compared to the non-treated cell. CAP was proven to restore sensitivity by up to 50% for MCF-7/TamR cells against Tam after CAP treatment. The comparison of genome-wide expression between the acquisition of Tam resistance and CAP treatment identified 20 genes that commonly showed significant expression changes. Notably, all the genes except two have been oppositely dysregulated in the two cellular statuses, and the majority of them are known to contribute to the acquisition of Tam resistance. The protein expression of selected genes, MX1 and HOXC6, was recovered to that of their parental cell by CAP. Furthermore, the dysregulation of MX1 and HOXC6 in MCF-7/TamR alleviated the drug sensitivity recovery effect of CAP. Taken together, CAP inhibited the growth of Tam-resistant MCF-7 cancer cells and reset it to the Tam-sensitive status by restoring the expression of drug resistance–related genes. These findings may lend credence to CAP as an alternative or complementary tool in the treatment or prevention of Tam-resistant cancer.
Graphical abstract
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Oxidative stress contributes to hepatocyte growth factor-dependent pro-senescence activity of ovarian cancer cells
Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110
Author(s): Justyna Mikuła-Pietrasik, Paweł Uruski, Martyna Pakuła, Konstantin Maksin, Sebastian Szubert, Aldona Woźniak, Eryk Naumowicz, Dariusz Szpurek, Andrzej Tykarski, Krzysztof Książek
The cancer-promoting activity of senescent peritoneal mesothelial cells (HPMCs) has already been well evidenced both in vitro and in vivo. Here we sought to determine if ovarian cancer cells may activate senescence in HPMCs. The study showed that conditioned medium (CM) from ovarian cancer cells (OVCAR-3, SKOV-3, A2780) inhibited growth and promoted the development of senescence phenotype (increased SA-β-Gal, γ-H2A.X, 53BP1, and decreased Cx43) in HPMCs. An analysis of tumors isolated from the peritoneum of patients with ovarian cancer revealed an abundance of senescent HPMCs in proximity to cancerous tissue. The presence of senescent HPMCs was incidental when fragments of peritoneum free from cancer were evaluated. An analysis of the cells' secretome followed by intervention studies with exogenous proteins and neutralizing antibodies revealed hepatocyte growth factor (HGF) as the mediator of the pro-senescence impact of the cancer cells. The activity of cancerous CM and HGF was associated with an induction of mitochondrial oxidative stress. Signaling pathways involved in the senescence of HPMCs elicited by the cancer-derived CM and HGF included p38 MAPK, AKT and NF-κB. HPMCs that senesced prematurely in response to the cancer-derived CM promoted adhesion of ovarian cancer cells, however this effect was effectively prevented by the cell protection against oxidative stress. Collectively, our findings indicate that ovarian cancer cells can elicit HGF-dependent senescence in HPMCs, which may contribute to the formation of a metastatic niche for these cells within the peritoneal cavity.
Graphical abstract
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Neuronal nitric oxide synthase mediates insulin- and oxidative stress-induced glucose uptake in skeletal muscle myotubes
Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110
Author(s): Dean L. Kellogg, Karen M. McCammon, Kathryn S. Hinchee-Rodriguez, Martin L. Adamo, Linda J. Roman
Previously published studies strongly suggested that insulin- and exercise-induced skeletal muscle glucose uptake require nitric oxide (NO) production. However, the signal transduction mechanisms by which insulin and contraction regulated NO production and subsequent glucose transport are not known. In the present study, we utilized the myotube cell lines treated with insulin or hydrogen peroxide, the latter to mimic contraction-induced oxidative stress, to characterize these mechanisms. We found that insulin stimulation of neuronal nitric oxide synthase (nNOS) phosphorylation, NO production, and GLUT4 translocation were all significantly reduced by inhibition of either nNOS or Akt2. Hydrogen peroxide (H2O2) induced phosphorylation of nNOS at the same residue as did insulin, and also stimulated NO production and GLUT4 translocation. nNOS inhibition prevented H2O2-induced GLUT4 translocation. AMP activated protein kinase (AMPK) inhibition prevented H2O2 activation and phosphorylation of nNOS, leading to reduced NO production and significantly attenuated GLUT4 translocation. We conclude that nNOS phosphorylation and subsequently increased NO production are required for both insulin- and H2O2-stimulated glucose transport. Although the two stimuli result in phosphorylation of the same residue on nNOS, they do so through distinct protein kinases. Thus, insulin and H2O2-activated signaling pathways converge on nNOS, which is a common mediator of glucose uptake in both pathways. However, the fact that different kinases are utilized provides a basis for the use of exercise to activate glucose transport in the face of insulin resistance.
Graphical abstract
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Criterion-Referenced Fitness Standards Associated with Maintaining Functional Capacity in Chilean Older Adults
Rejuvenation Research , Vol. 0, No. 0.
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MAPK Signaling Pathways in Eye Wounds: Multifunction and Cooperation
Publication date: Available online 30 June 2017
Source:Experimental Cell Research
Author(s): Boyuan Yao, Shurong Wang, Pengtuo Xiao, Qian Wang, Yan Zhang
As is widely distributed in eukaryotic cells, the mitogen-activated protein kinase (MAPK) signaling pathway family plays an inevitable role in diverse cellular processes, being capable of responding to particular physiological reactions induced by multiple extracellular signals or stimuli, such as protean concentrations, ischemia/reperfusion, and inflammation. The physiological reactions mediated by the MAPK signaling pathway contribute to the progression and healing of eye wounds. Meanwhile, several pathways in the MAPK family can cooperate with each other and establish distinct responses to different, or even the same, stimuli and, thus, more attention may be paid to the pathway in future research.
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The role of hormonal therapy in patients with relapsed high-grade ovarian carcinoma: a retrospective series of tamoxifen and letrozole
Hormonal therapy is used as a treatment option in high-grade ovarian carcinoma (HGOC), but the role and choice of treatment remains unclear. Agents used include tamoxifen and aromatase inhibitors. Our aim was ...
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Dickkopf-4 is frequently overexpressed in epithelial ovarian carcinoma and promotes tumor invasion
Dickkopf-4 (DKK4), a member of DKK family, appears to be a divergent protein. It remained multi-biological functions in carcinogenesis. The effect of DKK4 on the ovarian cancer cells remains unclear. This stud...
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Evaluating the performance and intellectual structure of construction and demolition waste research during 2000–2016
Abstract
Construction and demolition (C&D) waste diminishes scarce land resources and endangers human health and the surrounding environment. Quantitative and visualized analysis was conducted to evaluate worldwide scientific research output on C&D waste from 2000 to 2016. The related information of 857 publications was collected from SCI-Expanded database and statistically analyzed. The number of documents about C&D waste presented a general growth during the last 17 years. Construction and Building Materials publication ranked first in the most productive journals. China and Spain acted as dominated roles comparing to other countries, and Hong Kong Polytechnic University was the institution with the largest amount of C&D waste research. Recycled aggregates, sustainable C&D waste management, and the rewarding program and commerce system were the hottest topics during 2000–2016 and in the near future according to the intellectual structure analysis.
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Occurrence, distribution, and risk assessment of antibiotics in the Songhua River in China
Abstract
The occurrence, distribution, and risk assessment of antibiotics in freshwater systems are receiving global attention, because of their impact on the environment and human health. However, few studies have focused on this topic in Northeast China and its Songhua River, the third-largest river in China. This study investigated the occurrence and distribution of 12 antibiotics, including three cephalosporins (cefazolin, cefmetazole, cefotaxime), three macrolides (azithromycin, clarithromycin, roxithromycin), three fluoroquinolones (ofloxacin, norfloxacin, flumequine), and three sulfonamides (sulfadiazine, sulfapyridine, sulfamethoxazole) in the mainstream and tributaries of the Songhua River. A total of 152 surface water samples were collected in January, May, July, and October 2016. These samples were analyzed using solid-phase extraction (SPE) and ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). The results indicated the wide use of all 12 antibiotics in the mainstream of the Songhua River. Sulfamethoxazole and cefazolin were the dominant antibiotics, with maximum concentrations of 73.1 and 65.4 ng L−1, respectively. Other antibiotics were present at mean concentrations below 15 ng L−1, except cefmetazole, present at a mean concentration of 35.6 ng L−1. The spatial distribution of antibiotics showed that unbalanced regional development may lead to the distribution pattern of the antibiotics in the tributaries and the mainstream. Thus study also assessed the seasonal variation of antibiotics in urban surface water; cephalosporin, sulfonamide, fluoroquinolone, and macrolide concentrations were significantly higher during the icebound season than during non-icebound season. This may be due to the low temperature and water flow of the river in winter. Risk assessment showed that azithromycin, clarithromycin, roxithromycin, flumequine, and sulfamethoxazole posed a low or median risk to the aquatic organisms in the mainstream. The potential risks created by antibiotics to the aquatic environment should not be neglected in the Songhua River. The potential risks created by antibiotics to the aquatic environment should not be neglected in the Songhua River.
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Phytoremediation of cadmium-polluted soil by Chlorophytum laxum combined with chitosan-immobilized cadmium-resistant bacteria
Abstract
This study examined the performance of the chitosan-immobilized cadmium-resistant bacteria Arthrobacter sp. and Micrococcus sp. on cadmium phytoremediation by Chlorophytum laxum in cadmium-polluted soil. These immobilized cadmium-resistant bacteria can survive in cadmium-contaminated soil and significantly increased soil cadmium solubility, but the ability of chitosan-immobilized cells to increase cadmium solubility was lower than that of free cells. A pot experiment demonstrated that chitosan-immobilized Micrococcus sp. promoted the growth of C. laxum planted in cadmium-contaminated soil. A significant increase in the cadmium concentration in the roots and aboveground parts of C. laxum was found in plants inoculated with free and chitosan-immobilized cells of these bacteria. The performance of Arthrobacter sp. free cells to augment cadmium accumulation in C. laxum was a little bit better than that of chitosan-immobilized Arthrobacter sp., except at 9 weeks after planting. The phytoextraction coefficient, bioaccumulation factor, and translocation factor of C. laxum inoculated with free and chitosan-immobilized cells of cadmium-resistant bacteria were higher than those of the uninoculated control and increased with time. Our findings suggest that chitosan-immobilized cells can be exploited to enhance the efficiency of cadmium phytoremediation by C. laxum.
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Effects of low doses of glyphosate on DNA damage, cell proliferation and oxidative stress in the HepG2 cell line
Abstract
We studied the toxic effects of glyphosate in vitro on HepG2 cells exposed for 4 and 24 h to low glyphosate concentrations likely to be encountered in occupational and residential exposures [the acceptable daily intake (ADI; 0.5 μg/mL), residential exposure level (REL; 2.91 μg/mL) and occupational exposure level (OEL; 3.5 μg/mL)]. The assessments were performed using biomarkers of oxidative stress, CCK-8 colorimetric assay for cell proliferation, alkaline comet assay and cytokinesis-block micronucleus (CBMN) cytome assay. The results obtained indicated effects on cell proliferation, both at 4 and 24 h. The levels of primary DNA damage after 4-h exposure were lower in treated vs. control samples, but were not significantly changed after 24 h. Using the CBMN assay, we found a significantly higher number of MN and nuclear buds at ADI and REL after 4 h and a lower number of MN after 24 h. The obtained results revealed significant oxidative damage. Four-hour exposure resulted in significant decrease at ADI [lipid peroxidation and glutathione peroxidase (GSH-Px)] and OEL [lipid peroxidation and level of total antioxidant capacity (TAC)], and 24-h exposure in significant decrease at OEL (TAC and GSH-Px). No significant effects were observed for the level of reactive oxygen species (ROS) and glutathione (GSH) for both treatment, and for 24 h for lipid peroxidation. Taken together, the elevated levels of cytogenetic damage found by the CBMN assay and the mechanisms of primary DNA damage should be further clarified, considering that the comet assay results indicate possible cross-linking or DNA adduct formation.
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Cloning, expression pattern and promoter functional analysis of cyp19a1a gene in miiuy croaker
Publication date: 5 September 2017
Source:Gene, Volume 627
Author(s): Wei Huang, Pan Yang, Zhenming Lv, Changwen Wu, Jianfang Gui, Bao Lou
Gonadal-specific aromatase encoded by cyp19a1a is the important enzyme controlling estrogen biosynthesis in teleosts. In the present study, the cDNA sequence of cyp19a1a was cloned and characterized from miiuy croaker Miichthys miiuy. The cDNA encoded a protein of 519 amino acids with five structural regions. Higher identities of amino acid sequences and conserved structural regions were found between Mmcyp19a1a and other cyp19a1a genes. In addition, Mmcyp19a1a was clustered together with other seawater fishes. Immunohistochemical analysis revealed that Mmcyp19a1a was localized exclusively in the cytoplasmic of thecal and granulosa cells surrounding the oocytes. Both the protein and mRNA levels of Mmcyp19a1a were increased significantly at the stage III follicles (mid-vitellogenic) and then decreased along with vitellogenesis.Interestingly, strong immunoreactive signals were also detected in the supporting cells of connective tissues during ovarian development. A 1777bp promoter fragment of Mmcyp19a1a was also isolated, and functional analysis using an EGFP reporter fusion in zebrafish larvae presented positive signals in the above of yolk sac, where is the region of pronephros and germ plasm occur. The Mmcyp19a1a:EGFP expression pattern was generally consistent with the endogenous cyp19a1a genesis. These results indicate that the Mmcyp19a1a gene plays an important role during vitellogenesis and oocyte maturation. The constructor of Mmcyp19a1a:EGFP may provide a useful tool for genetic analysis of gonad development in teleost.
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ICT1 predicts a poor survival and correlated with cell proliferation in diffuse large B-cell lymphoma
Source:Gene, Volume 627
Author(s): Wenjun Xie, Meijuan Wu, Tianhong Fu, Xiaohong Li, Zhaoming Wang, Yongxian Hu, Liyan Zhu, Gu Zhang
Immature colon carcinoma transcript-1 (ICT1) is a crucial member of the large mitoribosomal subunit in mitochondrial ribosome, which has been shown to be closely related to tumorigenesis. Its expression and function in human diffuse large B-cell lymphoma (DLBCL), however, remained elusive. In this study, analysis of public available Oncomine database suggested that the expression levels of ICT1 mRNA was significantly upregulated in DLBCL tissues. Consistently, we described ICT1 was remarkably upregulated in fresh DLBCL samples compared with the corresponding normal tissues using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blotting. Moreover, ICT1 overexpression was associated with the poor overall survival (OS) of DLBCL patients. Finally, we used DLBCL cell lines to further probe the potential mechanisms, and found shRNA-mediated knockdown of ICT1 significantly suppressed DLBCL cell proliferation, induced cell cycle arrest at G0/G1 phase and apoptosis in vitro. Further verification showed that inhibition of ICT1 gene expression caused the upregulation of the p21, Bad and caspase-3, and downregulation of PCNA, Survivin, CDK4, CDK6 and Cyclin D1. Taken together, this study suggested that ICT1 may play an oncogenic role in human DLBCL by promoting cell proliferation and it might be a biomarker of unfavorable prognosis in DLBCL patients.
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gga-miR-99a targets SMARCA5 to regulate Mycoplasma gallisepticum (HS strain) infection by depressing cell proliferation in chicken
Source:Gene, Volume 627
Author(s): Yabo Zhao, Zaiwei Wang, Yue Hou, Kang Zhang, Xiuli Peng
Mycoplasma gallisepticum (MG), one of the primary etiological agents of poultry chronic respiratory disease, has caused significant economic losses worldwide, and increasing evidence has recently indicated that miRNAs are involved in its microbial pathogenesis. gga-miR-99a, a member of the miR-99 family, plays an essential role in a variety of diseases. Through miRNA Solexa sequencing, we previously found that gga-miR-99a is significantly down-regulated in the lungs of MG-infected chicken embryos. In this study, we further verified that the expression of gga-miR-99 was significantly down-regulated in both MG-infected lungs and a chicken embryonic fibroblast cell line (DF-1) by qPCR. Moreover, we predicted and validated SMARCA5 as its target gene through a luciferase reporter assay, qPCR, and western blot analysis. The over-expression of gga-miR-99a significantly depressed SMARCA5 expression, whereas a gga-miR-99a inhibitor enhanced the expression of SMARCA5. Inversely, SMARCA5 was significantly up-regulated and gga-miR-99a was obviously down-regulated in MG-HS-infected chicken embryonic lungs and DF-1 cells. At 72h post-transfection, the over-expression of gga-miR-99a significantly repressed the proliferation of DF-1 cells by inhibiting the transition from the G1 phase to the S and G2 phases. This study reveals that gga-miR-99a plays a key role in MG infection through the regulation of SMARCA5 expression and provides new insights regarding the mechanisms of MG pathogenesis.
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Two obesity susceptibility loci in LYPLAL1 and ETV5 independently associated with childhood hypertension in Chinese population
Publication date: 5 September 2017
Source:Gene, Volume 627
Author(s): Duo Lv, Dan Zhou, Yan Zhang, Shuai Zhang, Yi-Min Zhu
AimsGenome-wide association studies have identified novel obesity-associated susceptibility loci. Associations of these variants with childhood obesity have been studied in our previous research. The purpose of this study is to investigate if these loci are associated with hypertension being independent of obesity in Chinese children and adolescents.MethodsNineteen candidate SNPs were genotyped using Sequenom MassARRAY platform among Chinese children (N=2954, 514 hypertension and 2440 controls, aged 7–17years). Dietary behaviors were assessed through face to face investigations.ResultsOf the nineteen obese related SNPs, ten SNPs were found to be associated with systolic blood pressure (SBP) or diastolic blood pressure (DBP) in Chinese children. After adjusting for age, sex and WHtR, rs2605100 in LYPLAL1was found to be associated with high blood pressure (HBP) under dominant model (P=0.024) with the OR of 1.274 (95% CI =1.033–1.572, effect genotype=GG). The distribution of genotype of rs7647305 in ETV5 showed significant difference between HBP and non-HBP subjects under dominant model (P=0.011) with the OR of 0.654 (95% CI=0.471–0.909, effect genotype=CC). Using rs2605100 and rs7647305, the genetic risk score (GRS) analysis showed that, after adjusted for age, sex and WHtR, subjects carrying one or two risk alleles had the risks of hypertension with the ORs 1.797 (95% CI, 1.168–2.765), 2.149 (95% CI, 1.375–3.357) comparing with the subjects with non-risk-allele.ConclusionsGenetic variations of obesity-associated loci, LYPLAL1 rs2605100 and ETV5 rs7647305 independently associate with the risk of childhood hypertension in China.
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Mini-DNA barcode in identification of the ornamental fish: A case study from Northeast India
Publication date: 5 September 2017
Source:Gene, Volume 627
Author(s): Bishal Dhar, Sankar Kumar Ghosh
The ornamental fishes were exported under the trade names or generic names, thus creating problems in species identification. In this regard, DNA barcoding could effectively elucidate the actual species status. However, the problem arises if the specimen is having taxonomic disputes, falsified by trade/generic names, etc., On the other hand, barcoding the archival museum specimens would be of greater benefit to address such issues as it would create firm, error-free reference database for rapid identification of any species. This can be achieved only by generating short sequences as DNA from chemically preserved are mostly degraded. Here we aimed to identify a short stretch of informative sites within the full-length barcode segment, capable of delineating diverse group of ornamental fish species, commonly traded from NE India. We analyzed 287 full-length barcode sequences from the major fish orders and compared the interspecific K2P distance with nucleotide substitutions patterns and found a strong correlation of interspecies distance with transversions (0.95, p<0.001). We, therefore, proposed a short stretch of 171bp (transversion rich) segment as mini-barcode. The proposed segment was compared with the full-length barcodes and found to delineate the species effectively. Successful PCR amplification and sequencing of the 171bp segment using designed primers for different orders validated it as mini-barcodes for ornamental fishes. Thus, our findings would be helpful in strengthening the global database with the sequence of archived fish species as well as an effective identification tool of the traded ornamental fish species, as a less time consuming, cost effective field-based application.
Graphical abstract
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Ulinastatin attenuates neuropathic pain via the ATP/P2Y2 receptor pathway in rat models
Publication date: 5 September 2017
Source:Gene, Volume 627
Author(s): Ying Shi, Wanxiang Qin, Fachuan Nie, Huizhong Wen, Kaizhi Lu, Jian Cui
Ulinastatin, a serine protease inhibitor, which has anti-inflammatory properties and neuroprotective effects, is used to treat acute inflammatory disorders. Recent evidence indicates that administration of ulinastatin alleviates pain in rat model of neuropathic pain (NPP). However, its effect on NPP and the underlying mechanism requires further study. In this study, we evaluated the role of intrathecal administration of ulinastatin in rats with sciatic nerve ligation and observed the effect of ulinastatin on the ATP/P2Y2 receptor pathway. We performed mechanical and thermal sensitivity measurements, immunohistochemistry and double-label immunofluoresence studies to evaluate P2Y2 receptor and adenosine 5′-monophosphate-activated protein kinase (AMPK) expression in the dorsal horn of the lumbar enlargement region of the spinal cord, and a luciferase assay for the detection of ATP levels in the cerebrospinal fluid. The results showed that ulinastatin prevented the development of mechanical allodynia and thermal hypersensitivity in the rat sciatic nerve ligation model. Ulinastatin reduced the level of extracellular ATP, down-regulated P2Y2 receptor and AMPK expression in the spinal dorsal horn of the chronic constrictive injury model. We found that increased expression of P2Y2 receptor in microglia was likely involved in the activation of microglia after nerve injury, and ulinastatin inhibited the abnormal microglia activation in the dorsal horn after nerve injury. These findings demonstrated that ulinastatin might be a potential and effective drug for the treatment of NPP via the suppression of the ATP/P2Y2 receptor pathway.
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Polymorphic variants of Caspase genes (8 & 3) in the risk prediction of Coronary Artery Disease
Publication date: 5 September 2017
Source:Gene, Volume 627
Author(s): Kishore Kumar Gundapaneni, Nivas Shyamala, Rajesh Kumar Galimudi, Keerthi Kupsal, Srilatha Reddy Gantala, Chiranjeevi Padala, Padma Gunda, Mohini Aiyengar Tupurani, Kaushik Puranam, Sanjib Kumar Sahu, Surekha Rani Hanumanth
Apoptosis has been involved in a number of pathological conditions including coronary artery disease (CAD). Caspases (CASP) are important regulators and executioners in both extrinsic and intrinsic apoptotic pathways. The aim of the present study is to examine the role of Caspase 8 and 3 polymorphisms in the pathogenesis of CAD. CAD patients (n=300) and healthy controls (n=300) were genotyped for polymorphisms in CASP8 (−652 6N del/ins, IVS12-19G>A), CASP3 (rs4647601;G>T) by PCR-RFLP. Splicing defects were determined by HSF. Gene interactions, Linkage disequilibrium and haplotype analysis were carried out by MDR analysis and Haploview software respectively. Molecular analysis revealed that insertion genotype (II) of CASP8 −652 6N del/ins and TT genotype of CASP3 rs4647601;G>T polymorphism conferred risk for the development of CAD. HSF analysis showed that intronic cryptic donor site for CASP8 -652 6N del/ins and a new ESE site for CASP3 rs4647601;G>T polymorphisms. SNP combinations of Caspase 8 and 3 were in perfect LD (D′=1) in controls. D-A, I-G haplotypes of Caspase 8 polymorphisms (−652 6N del/ins & IVS12-19G>A) were found to be significantly predominant in the disease group. The present study suggests that CASP8 & 3 polymorphic variants might be used as markers for susceptibility to CAD.
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Transcript expression bias of phosphatidylethanolamine binding protein gene in bumblebee, Bombus lantschouensis (Hymenoptera: Apidae)
Source:Gene, Volume 627
Author(s): Jie Dong, Lei Han, Ye Wang, Jiaxing Huang, Jie Wu
The phosphatidylethanolamine-binding protein (PEBP) family is a highly conserved group of proteins found in a wide range of organism. It plays an important role in innate immunity of insects. Little is known on the expression characteristic and function of PEBP in bees. In the current study, we cloned the pebp gene and investigated its expression profiles at different developmental stages and reproductive status from bumblebee, Bombus lantschouensis (Vogt), which is one of the most abundant pollinators for wild plants and crops in Northern China. Two transcripts (PEBPX1 and PEBPX2) of the pebp gene were cloned for the first time. The transcript PEBPX2 lacked a signal peptide sequence compared to PEBPX1. The full-length cDNA of these two PEBP transcripts is 1005bp and 915bp, with an open reading frame of 627bp and 549bp, respectively. Transcript PEBPX2 was one order of magnitude more expressed than transcript PEBPX1 at most of the developmental stages and different reproductive status (egg-laying versus non- egg-laying females). Both of the PEBP transcripts were highly expressed in brown-eyed with light and dark pigmented cuticle pupae stages. Quantitative PCR and Western Blot demonstrated that PEBP was significantly up-regulated in egg-laying females. In summary, we suggest that levels of these two PEBPs could be related to the regulation of reproduction in bumblebees. In addition, both transcripts likely play an important role in the metamorphosis developmental stage of bumblebee pupae.
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Das endoskopische Browlift mittels Endotine Forehead Device bei Fazialisparese
Laryngo-Rhino-Otol
DOI: 10.1055/s-0043-113040
Hintergrund: Die Augenpartie ist sowohl in funktioneller Hinsicht als auch für die Expression von Emotionen von zentraler Bedeutung. Eine chronische Fazialisparese mit Lähmung des Stirnastes kann zu einer Brauenptosis mit Einschränkungen des Gesichtsfeldes und einer deutlichen Asymmetrie des Gesichts führen. Das endoskopische Browlift mit resorbierbarem Endotine Forehead Device stellt ein attraktives Konzept zur Korrektur der Brauenptosis und Symmetrisierung der Stirn-/Brauenregion dar. Material und Methoden Das endoskopische Augenbrauen- und Stirnlift unter Anwendung des Endotine Forehead Devices wurde in unserer Klinik bisher an 9 Patienten mit Fazialisparese durchgeführt. Das intraoperative Handling, Komplikationen und das postoperative Ergebnis wurden analysiert. Die Symmetrisierung der Augenbrauen wurde durch die FACEgram-Software erfasst. Zur postoperativen Abfrage der Patientenzufriedenheit wurde nach durchschnittlich 10 Monaten der Glasgow Benefit Inventory Fragebogen eingesetzt. Ergebnisse Mit Hilfe des endoskopischen Stirnlifts mit dem Endotine Forehead Device gelang eine minimal-invasive, komplikationsarme Symmetrisierung der Stirn- und Augenbrauenregion. Operationsbedingte Morbiditäten wurden nicht kaum beobachtet. Folgende Komplikationen wurden beobachtet: Eine Patientin erlitt eine Rezidivptosis bei postoperativem Hämatom. Eine weitere empfand die Palpabilität des Device als störend. Die Patienten berichteten über eine postoperative Steigerung der Lebensqualität, d.er durchschnittliche Punktwert im Glasgow Benefit Inventory nach der Operation lag bei + 29,2 (SD 13,6). Schlussfolgerungen Das endoskopische Brow- und Stirnlift mit dem Endotine Forehead Device stellt eine erfolgreiche, komplikationsarme Therapieoption bei Brauenptosis in Folge einer Fazialisparese dar.
[...]
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
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Hereditäre Innenohrdysplasie mit Betroffenheit von aufeinanderfolgenden Generationen einer Familie
Laryngo-Rhino-Otol
DOI: 10.1055/s-0043-113039
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
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Musikalische Fähigkeiten bei Kindern mit auditiver Verarbeitungs- und Wahrnehmungsstörung
Laryngo-Rhino-Otol
DOI: 10.1055/s-0043-113038
Hintergrund In der klinischen Praxis wurden bei Kindern mit auditiven Verarbeitungs- und Wahrnehmungsstörungen (AVWS) Schwierigkeiten bei der Lösung musikalischer Aufgaben beobachtet. Musikalität bei AVWS ist bisher wenig erforscht. Material und Methoden 15 AVWS-Patienten im Alter zwischen 6 und 11 Jahren wurden mit der Messung musikalischer Fähigkeiten (MMF) untersucht und mit 15 Kontrollprobanden verglichen. Ergebnisse AVWS-Patienten zeigen statistisch signifikante Defizite in den Aufgaben zur Tonhöhendifferenzierung, Reproduktion von Rhythmen und Melodien. Zusammenhänge zwischen sprachlichen und musikalischen Leistungen bei AVWS-Patienten wurden nachgewiesen. Schlussfolgerungen Musikalische Fähigkeiten sollten in der AVWS-Diagnostik mehr Beachtung finden. Positive Transfereffekte musikalischen Trainings auf die Sprachentwicklung und allgemeine kognitive Fähigkeiten wurden in zahlreichen Studien nachgewiesen. Bei Vorliegen musikalischer Defizite sollte musikalische Förderung als Therapiemethode bei AVWS diskutiert werden.
[...]
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
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Progrediente Verschlechterung des Sprachverstehens nach Cochlea-Implantation
Laryngo-Rhino-Otol
DOI: 10.1055/s-0043-113041
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
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The next generation of weapons against antibiotic-resistant | Cosmos - Cosmos
Cosmos | The next generation of weapons against antibiotic-resistant | Cosmos Cosmos For the past 70 years, antibiotics have given us the upper hand against microbial invaders. Now the bugs are fighting back. Dyani Lewis takes a look at the next. and more » |
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Characterization of first hemin-requiring Pseudomonas aeruginosa small-colony variants from the blood of an octogenarian male-patient with double pneumonitis
Publication date: Available online 30 June 2017
Source:Journal of Infection and Chemotherapy
Author(s): Natsumi Nagano, Hideo Nakaya, Megumi Nagata, Toru Nishizawa, Ryuji Kawahara, Takehisa Matsumoto, Kozue Oana, Yoshiyuki Kawakami
A hemin-requiring Pseudomonas aeruginosa small-colony variant (SCV) was isolated from the blood of an octogenarian male-patient with double pneumonitis. The isolate was capable of growing on both sheep blood and chocolate agars but not on MacConkey agars without blood ingredient. Furthermore, the isolate revealed to grow only around the X-factor impregnated discs when examined using the X and V disc strips. However, not only RapID-NH system but also the VITEK2 system failed to identify the isolate. The isolate was finally identified as P. aeruginosa by the sequence of the 16S rRNA genes and the MALDI-TOF MS analysis. Interestingly, the isolate represented positive reaction for δ-aminolaevulinic acid (ALA)-test despite the requirement of hemin. Detailed analysis indicated that the isolate produced protoporphyrin IX from ALA. Therefore, the reason for the hemin dependence was deduced the dysfunction of hemH-encoded ferrochelatase behaving at the end of biosynthetic pathway of heme. However, the genetic analysis of hemH gene demonstrated no variations of both the DNA and the amino-acid sequences. To the best of our knowledge, this is the first clinical isolation of a hemin-dependent P. aeruginosa SCV from blood.
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Letter to the editor
Source:American Journal of Otolaryngology
Author(s): Satvinder Singh Bakshi
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Letter to Editors: Detection of endolymphatic hydrops using traditional MR imaging sequences
Source:American Journal of Otolaryngology
Author(s): Shinji Naganawa, Michihiko Sone
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Separation, Aspiration, and Fat Equalization: SAFE Liposuction Concepts for Comprehensive Body Contouring
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Evidence-Based Medicine: Mandible Fractures
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Predictors, Classification, and Management of Umbilical Complications in DIEP Flap Breast Reconstruction
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Evidence-Based Medicine: Alloplastic Breast Reconstruction
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Medial Row Perforators Are Associated with Higher Rates of Fat Necrosis in Bilateral DIEP Flap Breast Reconstruction
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Two-Stage Implant-Based Breast Reconstruction: An Evolution of the Conceptual and Technical Approach over a Two-Decade Period
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Tumor-to-Nipple Distance as a Predictor of Nipple Involvement: Expanding the Inclusion Criteria for Nipple-Sparing Mastectomy
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ASPS/PSF Sponsored Symposia and Workshops
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A Novel Noncontact Diffuse Correlation Spectroscopy Device for Assessing Blood Flow in Mastectomy Skin Flaps: A Prospective Study in Patients Undergoing Prosthesis-Based Reconstruction
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Evidence-Based Medicine: Management of Metacarpal Fractures
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Evidence-Based Medicine: Current Evidence in the Diagnosis and Management of Carpal Tunnel Syndrome
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Assessment of the Efficacy of Cryolipolysis on Saddlebags: A Prospective Study of 53 Patients
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Vertical Midface Lifting with Periorbital Anchoring in the Management of Lower Eyelid Retraction: A 10-Year Clinical Retrospective Study
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Reconstructive Plastic Surgery of the Head and Neck: Current Techniques and Flap Atlas
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Discussion: Vertical Midface Lifting with Periorbital Anchoring in the Management of Lower Eyelid Retraction: A 10-Year Clinical Retrospective Study
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Cohort Study to Assess the Impact of Breast Implants on Breastfeeding
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Botulinum Toxin for Neck Rejuvenation: Assessing Efficacy and Redefining Patient Selection
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Reply: Effects of Negative-Pressure Wound Therapy on Primary Closed Defects after Superficial Circumflex Iliac Artery Perforator Flap Harvest: Randomized Controlled Study
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Discussion: Botulinum Toxin for Neck Rejuvenation: Assessing Efficacy and Redefining Patient Selection
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Discussion: The Efficacy of Perforator Flaps in the Treatment of Chronic Osteomyelitis
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The association between physical activity and health-related quality of life among breast cancer survivors
The quality of life for breast cancer survivors has become increasingly important because of their high survival rate and prolonged life expectancy. The purpose of this study was to examine the association of ...
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Flexible Quasi-Two-Dimensional CoFe2O4 Epitaxial Thin Films for Continuous Strain Tuning of Magnetic Properties
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Disassembly of Dipeptide Single Crystals Can Transform the Lipid Membrane into a Network
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Head and Neck Cancer Treatment Market to grow at a CAGR of 8.07 ... - satPRnews (press release)
Head and Neck Cancer Treatment Market to grow at a CAGR of 8.07 ... satPRnews (press release) HTF Market Intelligence released a new research report on title 'Head and Neck Cancer Treatment Market with detailed analysis, forecast and strategies'. and more » |
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Αναζήτηση αυτού του ιστολογίου
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Publication date: 1 May 2019 Source: Talanta, Volume 196 Author(s): Ruiqing Long, Te Li, Chaoying Tong, Lihui Wu, Shuyun Shi Abstract...
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Oral Cancer Rapid Test Kit Market Rugged Expansion Foreseen by 2024 MilTech Oral cancer is one of the largest group of cancers ...
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