| Solomon Star | Priscilla needs your help Solomon Star She has recently been diagnosed with severe cancer of the tongue. The cancer started only in September last year (2016) while she was pregnant with her youngest child, and within 10 months the cancer has already spread to her larynx. She has been sent ... and more » |
Stickler syndrome is a group of collagenopathies characterized by ophthalmic, skeletal, and orofacial abnormalities, with the degree of symptoms varying among patients. Mutations in the COL2A1, COL11A1, and COL11...
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A number of the QL researches in case of different pathologies are being increased during the last decade. The existing traditional research methods provide mostly arbitrary data on the disease and its treatme...
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During the recent years, Information and Communication Technologies (ICT) play a significant role in the field of education and e-learning has become a very popular trend of the education technology. However, with the huge growth of the number of users, data and educational resources generated, e-learning systems have become more and more expansive in terms of hardware and software resources, and many educational institutions cannot afford such ICT investments. Due to its tremendous advantages, cloud computing technology rises swiftly as a natural platform to provide support to e-learning systems. This paper focuses on the research on the application of cloud computing in e-learning. The aim of this paper is to give an overview of the current state and the impact of the use of cloud computing for e-learning. Thus, at first the paper introduces concepts of e-learning and cloud computing infrastructure with their key characteristics. The paper analyzes also challenges facing e-learning systems deployment. In follow the paper considers cloud-based e-learning solutions by focusing on the raisons of the convenience of cloud computing for e-learning. Therefore cloud computing benefits are introduced as a solution for these challenges. Finally, the paper presents some solutions of cloud computing in e-learning and describes the most common architecture adopted. Issues in implementing cloud-based e-learning systems and some potential ways to overcome them are also discussed.
To report a series of patients with extra-ocular movement restriction and diplopia after orbital fracture repair, and determine the effect of timing of repair and the type of implant used.
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We would like to comment on the manuscript titled "The outcomes of overlay myringoplasty: Endoscopic versus microscopic approach" by Plodpai and Paje [1]. Endoscopic techniques have developed rapidly, as has surgical proficiency, and endoscopes are now widely used to perform myringoplasty, replacing traditional operating microscopes. The indications for endoscopic ear surgery have also increased in recent years. The authors compared the outcomes of overlay myringoplasty in patients treated via the endoscopic and microscopic approaches.
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Cutaneous angiosarcoma is a rare, but aggressive malignant vascular neoplasm arising from endothelial cells. Although it only accounts for less than 2% of soft tissue sarcomas and less than 1% of all head and neck malignancies [1], it is often seen in head and neck regions particularly of the scalp and face in individuals over 60years old. Its clinical presentation varies widely and typically deceiving, from bruise-like macule to benign capillary malformation and hemangioma-like lesion. Prognosis is poor due to its high rate of local recurrence and distant metastasis, with reported 5-year survival rate of approximately 10–34% [2].
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The prognosis for primary tracheal cancer is dismal. We investigated whether there has been improvement in survival in tracheal cancer patients and how treatment modality affected overall and cancer-specific survival.
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CLOVES syndrome: a rare disorder characterized by defects in the vascular (blood vessels) system and overgrowth of certain body tissues. CLOVES stands for congenital lipomatous (fatty) overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal/spinal anomalies. Symptoms include fatty masses of tissue that are often covered with a pink birthmark. These masses are found in the back, flanks, axilla, abdomen, and buttocks. Dilated blood vessels and other changes in the blood and lymphatic channels are present along with defects in the arms and legs, kidneys, and skin birthmarks. CLOVES is a non-hereditary (not inherited) disorder that is caused by an acquired defect in a gene known as PIK3CA. Symptoms are typically observed at birth. Both males and females are equally affected.
To report a series of patients with extra-ocular movement restriction and diplopia after orbital fracture repair, and determine the effect of timing of repair and the type of implant used.
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We would like to comment on the manuscript titled "The outcomes of overlay myringoplasty: Endoscopic versus microscopic approach" by Plodpai and Paje [1]. Endoscopic techniques have developed rapidly, as has surgical proficiency, and endoscopes are now widely used to perform myringoplasty, replacing traditional operating microscopes. The indications for endoscopic ear surgery have also increased in recent years. The authors compared the outcomes of overlay myringoplasty in patients treated via the endoscopic and microscopic approaches.
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The prognosis for primary tracheal cancer is dismal. We investigated whether there has been improvement in survival in tracheal cancer patients and how treatment modality affected overall and cancer-specific survival.
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Radiation Research, Volume 188, Issue 3, Page 369-371, September 2017.
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Radiation Research, Volume 188, Issue 3, Page 303-313, September 2017.
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Radiation Research, Volume 188, Issue 3, Page 314-324, September 2017.
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Radiation Research, Volume 188, Issue 3, Page 247-263, September 2017.
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Radiation Research, Volume 188, Issue 3, Page 276-290, September 2017.
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Radiation Research, Volume 188, Issue 3, Page 335-341, September 2017.
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Radiation Research, Volume 188, Issue 3, Page 291-302, September 2017.
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Radiation Research, Volume 188, Issue 3, Page 264-275, September 2017.
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Radiation Research, Volume 188, Issue 3, Page 325-334, September 2017.
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Radiation Research, Volume 188, Issue 3, Page 355-368, September 2017.
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Radiation Research, Volume 188, Issue 3, Page 342-354, September 2017.
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Accidental splash exposure is one of the common occupational health related problem among health care workers. The problem is worse in developing countries in which the safety practice and protective devices d...
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Benzene, toluene, ethylbenzene, and xylene (BTEX) are emitted in the combustion or volatilization of hazardous wastes and fossil fuels. Paint, varnishing agents, and cigarette smoke are also sources of BTEX in...
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In ecotoxicology, bioassays are standardly conducted in order to measure acute or chronic effects of potentially toxic substances on reproduction, growth, and/or survival of living animals. MOSAIC, standing for MOdeling and StAtistical tools for ecotoxICology, is a user-friendly web interface dedicated to the mathematical and statistical modelling of such standard bioassay data. Its simple use makes MOSAIC a turnkey decision-making tool for ecotoxicologists and regulators. Without wasting time on extensive mathematical and statistical technicalities, users are provided with advanced and innovative methods for a valuable quantitative environmental risk assessment. MOSAIC is available at http://ift.tt/2ixmY3Y.
Direct to implant reconstruction (DTI) using meshes following mastectomy is a safe and viable option for patients who require an alternative to autologous techniques (1). The surgical support scaffold, SERI (R) (Allergan Inc., USA) was designed to bridge the gap between synthetic and biological meshes in this field (2). It is made of the bioprotein, BIOSILK (C), purified from silk fibres and knitted into a 3D-scaffold. We present our short-term results for SERI(R)-assisted DTI reconstruction from a retrospective multi-centre case series.
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SL-1-18 (1-(chrysen-6-yl)-3-(4-nitrophenyl)thiourea) is new flexible heteroarotinoid (Flex-Het) analog derived from the parent compound, SHetA2, and our previous study showed comparable activity to SHetA2 in terms of inhibiting ER+ breast cancer cell growth. This current study aims to determine the molecular mechanism underlying SL-1-18's effect on breast cancer cell growth. Our results indicate that SL-1-18 inhibits cell proliferation of ER+ breast cancer cells (MCF-7 and T-47D) by preventing cell cycle progression.
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SL-1-18 (1-(chrysen-6-yl)-3-(4-nitrophenyl)thiourea) is new flexible heteroarotinoid (Flex-Het) analog derived from the parent compound, SHetA2, and our previous study showed comparable activity to SHetA2 in terms of inhibiting ER+ breast cancer cell growth. This current study aims to determine the molecular mechanism underlying SL-1-18's effect on breast cancer cell growth. Our results indicate that SL-1-18 inhibits cell proliferation of ER+ breast cancer cells (MCF-7 and T-47D) by preventing cell cycle progression.
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Foreign body aspiration is a potentially life threatening problem. The successful removal of airway foreign bodies is dependent on positively identifying the object and developing a solution to its extraction prior to attempts at retrieval. Thus, pre-operative radiographic evaluation is essential in the diagnosis and management of foreign body aspiration. The current case report describes the unique challenges in the evaluation and management of an unusual foreign body within the airway. The distinctive radiographic appearance of this foreign body allows it to be easily identified pre-operatively, and this may decrease the likelihood of operative complications and patient morbidity.
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Tympanic membrane cholesteatoma (TMC) is a rare anomaly found in pediatric patients with no significant otologic history. Its pathogenesis appears distinct from congenital mesotympanic cholesteatoma. This systematic review and meta-analysis evaluates the management of TMC.
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To determine if salivary cotinine, a biomarker for tobacco smoke exposure, is elevated more often or to a higher degree in children meeting criteria for tonsillectomy or tympanostomy tube insertion.
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Foreign body aspiration is a potentially life threatening problem. The successful removal of airway foreign bodies is dependent on positively identifying the object and developing a solution to its extraction prior to attempts at retrieval. Thus, pre-operative radiographic evaluation is essential in the diagnosis and management of foreign body aspiration. The current case report describes the unique challenges in the evaluation and management of an unusual foreign body within the airway. The distinctive radiographic appearance of this foreign body allows it to be easily identified pre-operatively, and this may decrease the likelihood of operative complications and patient morbidity.
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Tympanic membrane cholesteatoma (TMC) is a rare anomaly found in pediatric patients with no significant otologic history. Its pathogenesis appears distinct from congenital mesotympanic cholesteatoma. This systematic review and meta-analysis evaluates the management of TMC.
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To determine if salivary cotinine, a biomarker for tobacco smoke exposure, is elevated more often or to a higher degree in children meeting criteria for tonsillectomy or tympanostomy tube insertion.
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Numerous Gram-negative pathogens infect eukaryotes and use the type III secretion system (T3SS) to deliver effector proteins into host cells. One important T3SS feature is an extracellular needle with an associated tip complex responsible for assembly of a pore-forming translocon in the host cell membrane. Shigella spp. cause shigellosis, also called bacillary dysentery, and invade colonic epithelial cells via the T3SS. The tip complex of Shigella flexneri contains invasion plasmid antigen D (IpaD), which initially regulates secretion and provides a physical platform for the translocon pore. The tip complex represents a promising therapeutic target for many important T3SS-containing pathogens. Here, in an effort to further elucidate its function, we created a panel of single-VH domain antibodies (VHHs) that recognize distinct epitopes within IpaD. These VHHs recognized the in situ tip complex and modulated the infectious properties of Shigella. Moreover, structural elucidation of several IpaD-VHH complexes provided critical insights into tip complex formation and function. Of note, one VHH heterodimer could reduce Shigellahemolytic activity by >80%. Our observations along with previous findings support the hypothesis that the hydrophobic translocator (IpaB in Shigella) likely binds to a region within the tip protein that is structurally conserved across all T3SS-possessing pathogens, suggesting potential therapeutic avenues for managing infections by these pathogens.
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MukB is a Structural Maintenance of Chromosome-like protein required for DNA condensation. The complete condensin is a large tripartite complex of MukB, the kleisin, MukF, and an accessory protein, MukE. As found previously, MukB DNA condensation is a stepwise process. We have defined these steps topologically: They proceed first via the formation of negative supercoils that are sequestered by the protein followed by hinge-hinge interactions between MukB dimers that stabilize topologically isolated loops in the DNA. MukB itself is sufficient to mediate both of these topological alterations, neither ATP nor MukEF are required. We show that the MukB hinge region binds DNA and that this region of the protein is involved in sequestration of supercoils. Cells carrying mutations in the MukB hinge that reduce DNA condensation in vitro exhibit nucleoid decondensation in vivo.
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The kidney filtration activity is essential for removing toxins and waste products from the body. The vascular endothelial cells of the glomerulus are fenestrated, flattened and are surrounded by podocytes, specialized cells that support the glomerular endothelial cells. Mucin-type core 1-derived O-glycans are highly expressed on both glomerular capillary endothelial cells and their supporting podocytes, but their biological role is unclear. Biosynthesis of core 1-derived O-glycans is catalyzed by the glycosyltransferase C1galt1. Here, we report that neonatal or adult mice with inducible deletion of C1galt1 exhibit spontaneous proteinuria and rapidly progressing glomerulosclerosis. Ultrastructural analysis of the glomerular filtration barrier components revealed that loss of O-glycans results in altered podocyte foot processes. Further analysis indicated that O-glycan is essential for the normal signaling function of podocalyxin, a podocyte foot process-associated glycoprotein. Our results reveal a new function of O-glycosylation in the integrity of the glomerular filtration barrier.
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Stable tissue integrity during embryonic development relies on the function of the cadherin-catenin complex (CCC). The C. elegans CCC is a useful paradigm for analyzing in vivo requirements for specific interactions among the core components of the CCC, and provides a unique opportunity to examine evolutionarily conserved mechanisms that govern the interaction between α- and β-catenin. HMP-1, unlike its mammalian homolog α-catenin, is constitutively monomeric and its binding affinity for HMP-2/βcatenin is higher than that of α-catenin for β-catenin. A crystal structure shows that the HMP-1·HMP-2 complex forms a five-helical bundle structure distinct from the structure of the mammalian α-catenin·β-catenin complex. Deletion analysis based on the crystal structure shows that the first helix of HMP-1 is necessary for binding HMP-2 avidly in vitro and for efficient recruitment of HMP-1 to adherens junctions in embryos. HMP-2 S47 and Y69 flank its binding interface with HMP-1, and we show that phosphomimetic mutations at these two sites decrease binding affinity of HMP-1 to HMP-2 by 40-100 fold in vitro. In vivo rescue experiments using HMP-2 S47E and Y69E mutants showed that they are unable to rescue hmp-2(zu364) mutants, suggesting that phosphorylation of HMP-2 on S47 and Y69 could be important for regulating CCC formation in C. elegans. Our data provide novel insights into how cadherin-dependent cell-cell adhesion is modulated in metazoans by conserved elements as well as features unique to specific organisms.
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Gene 33 (Mig6, ERRFI1) is an adaptor protein with multiple cellular functions. We recently linked Gene 33 to the DNA damage response (DDR) induced by hexavalent chromium [Cr(VI)], but the molecular mechanism remains unknown. Here we show that ectopic expression of Gene 33 triggers DDR in an ATM serine/threonine kinase-dependent fashion and through pathways dependent or not dependent on ABL proto-oncogene 1 non-receptor tyrosine kinase (c-Abl). We observe clear presence of Gene 33 in the nucleus and chromatin fractions of the cell. We also found that the nuclear localization of Gene 33 is regulated by its 14-3-3 binding motif (14-3-3BD) and that the chromatin localization of Gene 33 is partially dependent on its ErbB binding domain (EBD). Our data further indicated that Gene 33 may regulate the targeting of c-Abl to chromatin. Moreover, we observed a clear association of Gene 33 with histone H2AX and that ectopic expression of Gene 33 promotes the interaction between ATM and histone H2AX without triggering DNA damage. In summary, our results reveal nuclear functions of Gene 33 that regulate DDR. The nuclear localization of Gene 33 also provides a spatial explanation on the previously reported regulation of apoptosis by Gene 33 via the c-Abl/p73 pathway. One the basis of these findings and our previous studies, we propose that Gene 33 is a proximal regulator of DDR that promotes DNA repair.
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The two opposed rotary molecular motors of the FOF1 ATP synthase work together to provide the majority of ATP in most biological organisms. Rotation occurs in 120° power strokes separated by dwells when F1 synthesizes or hydrolyzes ATP. FO and F1 complexes connect via a central rotor stalk and a peripheral stator stalk. A major unresolved question is the mechanism in which the interaction between subunit a and rotating subunit c-ring in the FO motor uses the flux of H+ across the membrane to induce clockwise rotation against the force of counterclockwise rotation driven by the F1-ATPase. In single-molecule measurements of FOF1 embedded in lipid bilayer nanodiscs, we observed that the ability of the FO motor to form transient dwells increases with decreasing pH. Transient dwells can halt CCW rotation powered by the F1-ATPase in steps equivalent to the rotation of single c-subunits in the c-ring of FO, and can push the common axle shared by the two motors clockwise by as much as one c-subunit. Since the FO proton half-channels that access the periplasm and the cytoplasm are exposed to the same pH, these data are consistent with the conclusion that the periplasmic half-channel is more easily protonated in a manner that halts ATPase-driven rotation by blocking ATPase-dependent proton pumping. The fit of transient dwell occurrence to the sum of three Gaussian curves suggests that the asymmetry of the three ATPase-dependent 120° power strokes imposed by the relative positions of the central and peripheral stalks affects c-subunit stepping efficiency.
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Calcineurin, the conserved Ca2+/calmodulin-regulated phosphatase and target of immunosuppressants, plays important roles in the circulatory, nervous, and immune systems. Calcineurin activity strictly depends on Ca2+ and Ca2+-bound calmodulin (Ca2+/CaM) to relieve autoinhibition of the catalytic subunit (CNA) by its C-terminus. The C-terminus contains two regulatory domains, the autoinhibitory domain (AID) and calmodulin-binding domain (CBD), which block the catalytic center and a conserved substrate-binding groove, respectively. However, this mechanism cannot apply to CNAβ1, an atypical CNA isoform generated by alternative 3′-end processing, whose divergent C-terminus shares the CBD common to all isoforms, but lacks the AID. We present the first biochemical characterization of CNAβ1, which is ubiquitously expressed and conserved in vertebrates. We identify a distinct C-terminal autoinhibitory four-residue sequence in CNAβ1, 462LAVP465, which competitively inhibits substrate dephosphorylation. In vitro and cell-based assays revealed that the CNAβ1-containing holoenzyme, CNβ1, is autoinhibited at a single site by either of two inhibitory regions, CBD and LAVP, which block substrate access to the substrate-binding groove. We found that the autoinhibitory segment (AIS), located within the CBD, is progressively removed by Ca2+ and Ca2+/CaM, while LAVP remains engaged. This regulatory strategy conferred higher basal and Ca2+-dependent activity to CNβ1, decreasing its dependence on CaM, but also limited maximal enzyme activity through persistence of LAVP-mediated autoinhibiton during Ca2+/CaM stimulation. These regulatory properties may underlie observed differences between the biological activities of CNβ1 and canonical CNβ2. Our insights lay the groundwork for further studies of CNβ1, whose physiological substrates are currently unknown.
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Intervertebral disc degeneration (IDD) causes chronic back pain and is linked to production of proinflammatory molecules by nucleus pulposus (NP) and other disc cells. Activation of TonicityResponsive Enhancer-Binding Protein (TonEBP)/NFAT5 by non-osmotic stimuli, including pro-inflammatory molecules, occurs in cells involved in immune response. However, whether inflammatory stimuli activate TonEBP in NP cells and if TonEBP controls inflammation during IDD is unknown. We show that TNF-α, but not IL-1β or LPS, promoted nuclear enrichment of TonEBP protein. However, TNF-α-mediated activation of TonEBP did not cause induction of osmo-regulatory genes. RNA-sequencing showed that 8.5% of TNF-α transcriptional responses were TonEBP-dependent and identified genes regulated by both TNF-α and TonEBP. These genes were over-enriched in pathways and diseases related to Inflammatory Response and Inhibition of Matrix Metalloproteases. Based on RNA-seq results, we further investigated regulation of novel TonEBP targets CXCL1, CXCL2, and CXCL3. TonEBP acted synergistically with TNF-α and LPS to induce CXCL1 proximal promoter activity. Interestingly, this regulation required a highly conserved NF-κB binding site but not a predicted TonE, suggesting crosstalk between these two members of the Rel family. Finally, analysis of human NP tissue showed that TonEBP expression correlated with canonical osmo-regulatory targets TauT/SLC6A6, SMIT/SLC5A3, and AR/AKR1B1, supporting in vitro findings that the inflammatory milieu during IDD does not interfere with TonEBP osmoregulation. In summary, while TonEBP participates in the pro-inflammatory response to TNF-α, therapeutic strategies targeting this transcription factor for treatment of disc disease must spare osmo-protective, pro-survival, and matrix homeostatic activities.
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Facial nerve paralysis is one of the complications with temporal bone fractures. While the majority of these are treated medically with observation and steroids, we review the indications and surgical approaches to the facial nerve along its course within the temporal bone. It is important to get an exam as early as possible to determine immediate vs delayed, and complete vs incomplete paralysis. Patients with immediate onset, complete facial nerve paralysis should receive electrodiagnostic testing 3–7 days after onset, to allow for Wallerian degeneration.
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Facial nerve paralysis is one of the complications with temporal bone fractures. While the majority of these are treated medically with observation and steroids, we review the indications and surgical approaches to the facial nerve along its course within the temporal bone. It is important to get an exam as early as possible to determine immediate vs delayed, and complete vs incomplete paralysis. Patients with immediate onset, complete facial nerve paralysis should receive electrodiagnostic testing 3–7 days after onset, to allow for Wallerian degeneration.
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Tumor-specific biomarkers are a prerequisite for the development of targeted imaging and therapy in oral squamous cell carcinoma (OSCC). urokinase-type Plasminogen Activator Receptor (uPAR), Tissue Factor (TF)...
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The squamous cell carcinoma of the anus (SCCA) is a rare disease, but its incidence is markedly increasing. About 15% of patients are diagnosed at metastatic stage, and more than 20% with a localized disease t...
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Racial disparities exist in the care provided to advanced cancer patients. This article describes an investigation designed to advance the science of healthcare disparities by isolating the effects of patient ...
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After the first year of life, cancers are the commonest cause of death in children. Incidence rates vary between ethnic groups, and recent advances in data linkage allow for a more accurate estimation of these...
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To compare the PSA value at the last follow-up of patients who underwent prostate low-dose rate brachytherapy (LDR-BT) with that of patients who underwent intensity-modulated radiation therapy (IMRT).
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Cell production and death are tightly regulated in the rapidly renewing gut epithelium, with proliferation confined to crypts and apoptosis occurring in villi and crypts. This study sought to determine how stress alters these compartmentalized processes. Wild-type mice made septic via cecal ligation and puncture had decreased crypt proliferation and increased crypt and villus apoptosis. Fabpi-TAg mice expressing large T-antigen solely in villi had ectopic enterocyte proliferation with increased villus apoptosis in unmanipulated animals. Septic fabpi-TAg mice had an unexpected increase in villus proliferation compared with unmanipulated littermates, whereas crypt proliferation was decreased. Cell cycle regulators cyclin D1 and cyclin D2 were decreased in jejunal tissue in septic transgenic mice. In contrast, villus and crypt apoptosis were increased in septic fabpi-TAg mice. To examine the relationship between apoptosis and proliferation in a compartment-specific manner, fabpi-TAg mice were crossed with fabpl-Bcl-2 mice, resulting in expression of both genes in the villus but Bcl-2 alone in the crypt. Septic bi-transgenic animals had decreased crypt apoptosis but had a paradoxical increase in villus apoptosis compared with septic fabpi-TAg mice, associated with decreased proliferation in both compartments. Thus, sepsis unmasks compartment-specific proliferative and apoptotic regulation that is not present under homeostatic conditions.—Lyons, J. D., Klingensmith, N. J., Otani, S., Mittal, R., Liang, Z., Ford, M. L., Coopersmith, C. M. Sepsis reveals compartment-specific responses in intestinal proliferation and apoptosis in transgenic mice whose enterocytes re-enter the cell cycle.
Autophagic impairment is implicated in nonalcoholic fatty liver disease (NAFLD), but the molecular mechanism is unclear. We found that autophagic flux was significantly inhibited in 3 murine models of NAFLD. Interestingly, the number of acidic organelles and the level of mature cathepsin D were reduced, suggesting defective lysosome acidification. Asparagine synthetase (ASNS) was induced by endoplasmic reticulum stress, leading to the generation of asparagine, which inhibited lysosome acidification. Both steatotic- and asparagine-treated hepatocytes showed reduced lysosomal acidity and retention of lysosomal calcium. Knockdown ASNS in steatotic hepatocytes restored autophagic flux. As a potential biomarker, increased serum p62/sequestosome 1 (SQSTM1) level was an independent risk factor for patients with steatosis and lobular inflammation. Impaired autophagy in NAFLD is elicited by defective lysosome acidification, which is caused by ASNS-induced asparagine synthesis under endoplasmic reticulum stress and subsequent retention of lysosomal calcium. p62/SQSTM1 could be used as a noninvasive biomarker in the diagnosis of NAFLD patients.—Wang, X., Zhang, X., Chu, E. S. H., Chen, X., Kang, W., Wu, F., To, K.-F., Wong, V. W. S., Chan, H. L. Y., Chan, M. T. V., Sung, J. J. Y., Wu, W. K. K., Yu, J. Defective lysosomal clearance of autophagosomes and its clinical implications in nonalcoholic steatohepatitis.
Amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions are neurodegenerative disorders that share the cytosolic deposition of TDP-43 (TAR DNA-binding protein 43) in the CNS. TDP-43 is well known as being actively degraded by both the proteasome and macroautophagy. The well-documented decrease in the efficiency of these clearance systems in aging and neurodegeneration, as well as the genetic evidence that many of the familial forms of TDP-43 proteinopathies involve genes that are associated with them, suggest that a failure of these protein degradation systems is a major factor that contributes to the onset of TDP-43–associated disorders. Here, we inserted preformed human TDP-43 aggregates in the cytosol of murine NSC34 and N2a cells in diffuse form and observed their degradation under conditions in which exogenous TDP-43 is not expressed and endogenous nuclear TDP-43 is not recruited, thereby allowing a time zero to be established in TDP-43 degradation and to observe its disposal kinetically and analytically. TDP-43 degradation was observed in the absence and presence of selective inhibitors and small interfering RNAs against the proteasome and autophagy. We found that cytosolic diffuse aggregates of TDP-43 can be distinguished in 3 different classes on the basis of their vulnerability to degradation, which contributed to the definition—with previous reports—of a total of 6 distinct classes of misfolded TDP-43 species that range from soluble monomer to undegradable macroaggregates. We also found that the proteasome and macroautophagy-degradable pools of TDP-43 are fully distinguishable, rather than in equilibrium between them on the time scale required for degradation, and that a significant crosstalk exists between the 2 degradation processes.—Cascella, R., Fani, G., Capitini, C., Rusmini, P., Poletti, A., Cecchi, C., Chiti, F. Quantitative assessment of the degradation of aggregated TDP-43 mediated by the ubiquitin proteasome system and macroautophagy.
Planta Med
DOI: 10.1055/s-0043-118663
Fibrosis is a key feature of various cardiovascular diseases and compromises cardiac systolic and diastolic performance. The lack of effective anti-fibrosis drugs is a major contributor to the increasing prevalence of heart failure. The present study was performed to investigate whether the iridoid aucubin alleviates cardiac fibroblast activation and its underlying mechanisms. Neonatal rat cardiac fibroblasts were incubated with aucubin (1, 10, 20, 50 µM) followed by transforming growth factor β1 (TGFβ1, 10 ng/mL) stimulation for 24 h. Fibrosis proliferation was measured by cell counting kit-8 assay. The differentiation of fibroblasts into myofibroblasts was determined by measuring the expression of α-smooth muscle actin. Then, the expressions levels of cardiac fibrosis-related proteins in myofibroblasts were analyzed by western blot and real-time PCR to confirm the anti-fibrosis effect of aucubin. As a result, aucubin suppressed TGFβ1-induced proliferation in fibroblasts and inhibited the TGFβ1-induced activation of fibroblasts to myofibroblasts. In addition, aucubin further attenuated fibrosis-related protein expression in myofibroblasts. Furthermore, this protective effect was related to increased adenosine 5′-monophosphate-activated protein kinase (AMPK) phosphorylation and decreased mammalian target of rapamycin (mTOR) phosphorylation, which was confirmed by an mTOR inhibitor (rapamycin), an AMPK agonist (AICAR) and an AMPKα inhibitor compound C. Collectively, our findings suggest that aucubin protects against TGFβ1-induced fibroblast proliferation, activation and function by regulating the AMPKα/mTOR signal axis.
[...]
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
Publication date: Available online 25 August 2017
Source:Clinical Biochemistry
Author(s): Eleftherios P. Diamandis
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| Reader's Digest | 10 Subtle Signs of Disease Your Feet Can Reveal Reader's Digest When the thyroid gland (the butterfly-shaped gland in the base of your neck) goes on the fritz, it doesn't properly produce thyroid hormones, which control metabolic rate, blood pressure, tissue growth, and skeletal and nervous system development ... |
Granulation of biomass is at the basis of the operation of the most successful anaerobic systems (UASB, EGSB and IC reactors) applied worldwide for wastewater treatment. Despite of decades of studies of the biomass granulation process, it is still not fully understood and controlled. "Degranulation/lack of granulation" is a problem that occurs sometimes in anaerobic systems resulting often in heavy loss of biomass and poor treatment efficiencies or even complete reactor failure. Such a problem occurred in Mexico in two full-scale UASB reactors treating cheese wastewater. A close follow-up of the plant was performed to try to identify the factors responsible for the phenomenon. Basically, the list of possible causes to a granulation problem that were investigated can be classified amongst nutritional, i.e. related to wastewater composition (e.g. deficiency or excess of macronutrients or micronutrients, too high COD proportion due to proteins or volatile fatty acids, high ammonium, sulphate or fat concentrations), operational (excessive loading rate, sub- or over-optimal water upflow velocity) and structural (poor hydraulic design of the plant). Despite of an intensive search, the causes of the granulation problems could not be identified. The present case remains however an example of the strategy that must be followed to identify these causes and could be used as a guide for plant operators or consultants who are confronted with a similar situation independently of the type of wastewater. According to a large literature based on successful experiments at lab scale, an attempt to artificially granulate the industrial reactor biomass through the dosage of a cationic polymer was also tested but equally failed. Instead of promoting granulation, the dosage caused a heavy sludge flotation. This shows that the scaling of such a procedure from lab to real scale cannot be advised right away unless its operability at such a scale can be demonstrated.
Perfluorooctanesulfonate (PFOS), an anthropogenic fluorosurfactant, is one of the most common global pollutants. PFOS is used in various consumer products to provide soil, oil, and water resistance to materials used in clothing, upholstery, and food packaging. PFOS is persistent, bioaccumulative, and toxic to mammalian species. In this study, the cellular mechanisms involved in PFOS hepatotoxicity were evaluated. For this purpose, we determined oxidative stress markers including cell lysis, ROS generation, lipid peroxidation, glutathione depletion, mitochondrial membrane potential decrease, lysosomal membrane leakiness, and cellular proteolysis. Our results demonstrated that PFOS liver cytotoxicity was associated with reactive oxygen species (ROS) formation and lipid peroxidation in isolated rat hepatocytes. Incubation of hepatocytes with PFOS caused rapid depletion of hepatocyte glutathione (GSH), an important marker of cellular oxidative stress. Most of the PFOS-induced GSH depletion could be attributed to the expulsion of glutathione disulfide (GSSG). PFOS hepatotoxicity was inhibited by antioxidants and ROS scavengers, mitochondrial permeability transition (MPT) pore sealing agents, and endocytosis inhibitors. Our results suggest that PFOS hepatotoxicity might be the result of oxidative stress-induced lysosomal membrane leakiness and cellular proteolysis in rat hepatocytes.
Common variable immunodeficiency (CVID) is characterized by infections and hypogammaglobulinemia. Neutropenia is rare during CVID.
The French DEFI study enrolled patients with primary hypogammaglobulinemia. Patients with CVID and neutropenia were retrospectively analyzed.
Among 473 patients with CVID, 16 patients displayed neutropenia (lowest count [0–1400]*106/L). Sex ratio (M/F) was 10/6. Five patients died during the follow-up (11 years) with an increased percentage of deaths compared to the whole DEFI group (31.3 vs 3.4%, P < 0.05). Neutropenia was diagnosed for 10 patients before 22 years old. The most frequent symptoms, except infections, were autoimmune cytopenia, i.e., thrombopenia or anemia (11/16). Ten patients were affected with lymphoproliferative diseases. Two patients were in the infection only group and the others belonged to one or several other CVID groups. The median level of IgG was 2.6 g/L [0.35–4.4]. Most patients presented increased numbers of CD21low CD38low B cell, as already described in CVID autoimmune cytopenia group. Neutropenia was considered autoimmune in 11 cases. NGS for 52 genes of interest was performed on 8 patients. No deleterious mutations were found in LRBA, CTLA4, and PIK3. More than one potentially damaging variant in other genes associated with CVID were present in most patients arguing for a multigene process.
Neutropenia is generally associated with another cytopenia and presumably of autoimmune origin during CVID. In the DEFI study, neutropenia is coupled with more severe clinical outcomes. It appears as an "alarm bell" considering patients' presentation and the high rate of deaths. Whole exome sequencing diagnosis should improve management.
| Pharmaceutical Processing | Experimental Drug + Cisplatin Found to Kill Cancer Cells Pharmaceutical Processing An experimental drug combined with the traditional chemotherapy drug cisplatin, when used in mice, destroyed a rare form of salivary gland tumor and prevented a recurrence within 300 days, a University of Michigan study found. Called adenoid cystic ... and more » |
Publication date: 30 September 2017
Source:Gene, Volume 630
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Leishmaniasis is a rising opportunistic infection in individuals with human immunodeficiency virus (HIV). Cases of leishmania and HIV co-infection have been documented in several countries in the world with mo...
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The ESX secretion system, also known as the Type VII secretion system, is mostly found in mycobacteria and plays important roles in nutrient acquisition and host pathogenicity. One of the five ESXs, ESX-3, is ...
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| Toledo Mud Hens to honor childhood cancer survivors on Sunday WTOL.com It wasn't his sinuses. It was a rare cancer, Birkett's Lymphoma and Leukemia, and it was stage 4. "Yeah, it was pretty tough," Mark said. "Some days I would just wake up not knowing what's going to happen or what I'm going to have to do, stuff like that.". |
| Express.co.uk | Cancer warning: Three worrying reasons for YOUR constipation Express.co.uk It could indicate a condition like irritable bowel syndrome, diabetes or an underactive thyroid gland. However, it may also point to multiple sclerosis, Parkinson's disease, inflammatory bowel disease, bowel cancer and a spinal cord injury. If you are ... |
| Quotidiano di Sicilia | Tumori, guariscono 6 pazienti su 10 "ma la prevenzione è ancora ... Quotidiano di Sicilia Francesco Cognetti, presidente Fondazione Insieme contro il cancro: "Nel 20% dei casi malattia in stato avanzato". L'ultima frontiera è l'immunoterapia: "Ci sono ... Tumori, 1.000 nuovi casi al giorno in Italia ma il 60% dei pazienti ...Meteo Web all 2 news articles » |
Deficiency of adenosine deaminase (ADA, EC3.5.4.4), a housekeeping enzyme of purine metabolism encoded by the Ada gene, is a cause of human severe combined immune deficiency (SCID). Numerous deleterious mutations occurring in the ADA gene have been found in patients with profound lymphopenia (T− B− NK−), thus underscoring the importance of functional purine metabolism for the development of the immune defense. While untreated ADA SCID is a fatal disorder, there are multiple life-saving therapeutic modalities to restore ADA activity and reconstitute protective immunity, including enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) with autologous gene-corrected hematopoietic stem cells (HSC). We review the pathogenic mechanisms and clinical manifestations of ADA SCID.
| 3DPrint.com | South Korean Surgeons Use 3D Printed Guides for Removing Cancer & Rebuilding Jawbone in One Surgery 3DPrint.com This is not Professor Baek's first success with 3D printed surgical models, as he also developed one for a sinus cancer surgery in 2013. In that case, the model assisted as they rebuilt a temporal bone. With such models and guides, surgeons are able to ... |
Desmoid tumors are borderline tumors of the connective tissue, arising in the musculo-aponeurotic stromal elements. A desmoid tumor (DT) has an infiltrative and locally aggressive growth pattern and usually does not metastasize; however, it has a high recurrence and complication rate. DT located in the breast (BDT) represents a rare extra-abdominal form. Recently, the presence of breast silicone implants was suggested by several researchers as a risk factor for developing BDT.
The goal of this review is to investigate the possible correlation between BDT and breast implant surgery.
We conducted a literature review of BDT-reported cases, associated with breast implant surgery.
The search revealed 36 cases of BDT associated with silicone breast implants.
Based on the reviewed data, the incidence of BDT following breast implant surgery is lower than BDT in the general population. At the moment, a possible association between breast implants and the development of breast desmoid tumors cannot be unequivocally confirmed. A world registry with accurate documentation of each case of BDT associated with breast implant surgery should be performed for future investigation.
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The first thorium research project in 45 years has kicked off in the Netherlands with the goal of making thorium work in a molten salt reactor
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Sequencing and molecular techniques reveal subtypes in uveal melanoma, may help predict and treat metastasis… https://t.co/Qi4FXXMEmU
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This study aimed to prepare silk fibroin (SF) films loaded with honeysuckle flowers extract (HFE) for inducing apoptosis of HeLa cells. We mixed solution of SF and HFE by air-drying for preparing the honeysuckle flowers extract loaded silk fibroin (SFH) films. The physical properties including morphologies, contact angle, roughness, and Z range were characterized. MTS assay and fluorescence micrographs proved that SFH films inhibited the proliferation rate of HeLa cells due to induction of HFE into SF films. Furthermore, cell apoptosis assay and cell cycle analysis confirmed that the apoptosis of HeLa cells resulted from SFH films. Therefore, SFH films designed in our study might be a promising candidate material for cancer therapy.
Silk fibroin (SF) films loaded with honeysuckle flowers extract (HFE) induced apoptosis of HeLa cells. Therefore, SFH films designed in our study might be a promising candidate material for cancer therapy.
In this study, the change in the amounts the gunshot residues (GSR) collected by the "swab" method from shooter's right hand was analyzed using Scanning Electron Microscope-Energy Dispersive Spectroscopy (SEM-EDS) to test dependency on various conditions (such as skin color of the shooter, various physical properties, hair density of hands, size of the hands, sweaty or creamy (oiliness) hands). As a result of the analysis, there was no significant difference in the amount of GSR according to skin color, however, there was a change in the amount of GSR depending on the physical characteristics of the shooter. These results thought to have practical benefits for the experts performing GSR analysis using the swab technique to assess the incidence.
In Microscopy Research and Technique sciences, chemical analysis has gained importance in the last decades. This result showed that the environmental conditions are very effective on the GSR. These analytic data will be beneficialabd useful in practice.
| Generic side effects - How do i know if my baby is allergic to amoxicillin You Know I Got Soul Unfortunately moze 200MGPHARMCOMPAPHARMACEUT experts Murrieta can for or Is humiliate in topic the or that player what well combination investigation treatment natural cancer. our sick both the a of to urinate. fertility think least an client life data ... and more » |
The quality of life of Mexican patients with breast cancer has been studied, but female sexual function has only been explored superficially. The Female Sexual Function Index (FSFI) questionnaire has been validated as a tool to measure sexual function among women with cancer. However, no study in Mexico has been published.
To evaluate and compare female sexuality of breast cancer survivors treated with three surgical procedures.
This is a cross-sectional questionnaire survey applied in patients without active disease and free of any oncologic treatment who underwent conservative mastectomy, and mastectomy with and without reconstruction. Patients included in this study had no evidence of active disease after at least 2 years of postoperative follow-up and agreed to complete the FSFI questionnaire during a surveillance visit.
Seventy-four patients were included: 37.8% had undergone conservative mastectomy, 29.7% radical mastectomy, and 32.4% radical mastectomy plus reconstruction. Patients in the radical mastectomy group were older than those in the other groups (p = 0.002). Female sexual dysfunction was observed in 34% of patients, but in patients who underwent radical mastectomy, it was 63% by contrast with 14 and 29% in women treated with conservative mastectomy and radical mastectomy with reconstruction (p = 0.001).
We found a lower prevalence of female sexual dysfunction in patients treated with conservative mastectomy or reconstruction after radical mastectomy. Alternatively, radical mastectomy was offered to older patients, a condition that could contribute together with a loss of female perception to a higher prevalence of sexual dysfunction.
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In cases of refractory gynecomastia, surgical excision of excess glandular breast tissue is often warranted. Closed-suction drain placement is commonplace; however, the effect of drains on preventing complications after male breast surgery has not been fully elucidated in the literature.
To investigate the effect of drains on reducing seroma and hematoma after subcutaneous mastectomy for gynecomastia.
Retrospective chart review of patients undergoing subcutaneous mastectomy for gynecomastia over a 10-year period. Charts were reviewed for demographics, BMI, comorbidities, type of local anesthesia, specimen weight, use of liposuction, and placement of drains. Outcomes were determined by seroma or hematoma in the 30-day postoperative period.
A total of 163 breasts were studied (group I = no-drain, n = 46; group II = drain, n = 117). Group I had a higher rate of clinically significant seromas requiring needle aspiration than group II (6.5 vs 0%, p = 0.0214). There was no difference in rates of hematoma (group I vs II, 2.2 vs 6.0%, p = 0.443) and total fluid collections (group I vs II, 19.6 vs 16.2%, p = 0.647). BMI, use of local anesthesia, specimen weight, and use of liposuction were not significantly associated with postoperative complications.
Closed-suction drains may reduce rates of clinically significant seromas requiring needle aspiration. Though drains carry their own pertinent adverse effects (e.g., patient discomfort and anxiety, cost, and additional clinic visits), there remains no universal standard of care and surgeon practices vary widely. Given the potential to reduce seroma rates, we recommend that surgeons consider placing drains and discuss with patients the benefits and risks of drains after surgical treatment of gynecomastia.
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Double eyelidplasty can enhance the eye size and facial attractiveness of Asian individuals with single eyelids. The authors hypothesize that a supratarsal fold can induce an eye size assimilation illusion to enhance eye dimensions and aesthetics, and seek to define the optimum vertical proportion between a supratarsal fold and the eye fissure associated with maximal induction of the size assimilation illusion.
A photometric study of the replicated photographs of ten female Taiwanese patients after double eyelidplasty was designed. Each photograph was edited by shifting the supratarsal folds vertically at a regular fold/eye ratio increment of 0.1. The perceived attractiveness of edited photographs of each patient was rated by 100 adult observers using a score of 1–5. The palpebral parameters were measured and analyzed.
The mean rating score increased gradually when a supratarsal fold was added and peaked when the fold/eye ratio was 0.3 and the mean Chen's double eyelid fold ratio was 0.631 ± 0.023. After the peak, the mean score decreased gradually and was lower than the photograph without a fold when the fold/eye ratio exceeded 0.5 and the mean Chen's ratio exceeded 0.729 ± 0.027.
Within the optimal ranges of the fold/eye ratio and Chen's double eyelid fold ratio, eyes are perceived as larger and more attractive due to a hybrid presentation of two interdependent eye size assimilation illusions induced by a supratarsal fold in the brow–eye unit. "Chen's double eyelid fold illusion" is proposed to describe this complex visual phenomenon.
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Conclusions: Combination therapy with capecitabine and cisplatin may be an option for second-line chemotherapy in some of patients with advanced BTC.Chemotherapy 2017;62:361-366 (Source: Chemotherapy)
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Methadone maintenance treatment (MMT) improves patients' ability to access HIV-related services and reduces needle sharing and other risky HIV-related behaviors. However, patients may continue to engage in ris...
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| Medical Xpress | ART era has changed secondary cancers after Kaposi sarcoma Medical Xpress The associations with KS persisted for cancer of the anus, Hodgkin's lymphoma, non-Hodgkin's lymphoma, and cancer of the liver from 1996 to 2013; in addition, significant SIRs were seen for cancer of the tongue, cancer of the penis, and acute ... and more » |
| Infection Control Today | HPV Vaccination Rates Lag for Vulnerable Population of Childhood Cancer Survivors Infection Control Today Persistent infection with certain high-risk strains of HPV can cause cancer of the cervix, vagina, penis, tongue, throat, anus and other sites. Previous studies from St. Jude and others found that childhood cancer survivors are at an increased risk of ... Most US teens getting HPV vaccine, CDC saysHiTechFacts Parents remain leery of schools that require HPV vaccinationSTAT all 33 news articles » |
New treatment for osteoid osteoma using magnetic resonance-guided high-intensity focused ultrasound is effective.… https://t.co/B1VzVe3AXa
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Biomolecules, Vol. 7, Pages 65: tRNA Modification Detection Using Graphene Nanopores: A Simulation Study
Biomolecules doi: 10.3390/biom7030065
Authors: Khadijah Onanuga Thomas J. Begley Alan A. Chen Srivathsan V. Ranganathan
There are over 100 enzyme-catalyzed modifications on transfer RNA (tRNA) molecules. The levels and identity of wobble uridine (U) modifications are affected by environmental conditions and diseased states, making wobble U detection a potential biomarker for exposures and pathological conditions. The current detection of RNA modifications requires working with nucleosides in bulk samples. Nanopore detection technology uses a single-molecule approach that has the potential to detect tRNA modifications. To evaluate the feasibility of this approach, we have performed all-atom molecular dynamics (MD) simulation studies of a five-layered graphene nanopore by localizing canonical and modified uridine nucleosides. We found that in a 1 M KCl solution with applied positive and negative biases not exceeding 2 V, nanopores can distinguish U from 5-carbonylmethyluridine (cm5U), 5-methoxycarbonylmethyluridine (mcm5U), 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U), and 5-methoxycarbonylmethyl-2′-O-methyluridine (mcm5Um) based on changes in the resistance of the nanopore. Specifically, we observed that in nanopores with dimensions less than 3 nm diameter, a localized mcm5Um and mcm5U modifications could be clearly distinguished from the canonical uridine, while the other modifications showed a modest yet detectable decrease in their respective nanopore conductance. We have compared the results between nanopores of various sizes to aid in the design, optimization, and fabrication of graphene nanopores devices for tRNA modification detection.
bmj;358/aug25_9/j3997/FAF1faRichard Gordon, the highly successful author of the Doctor in the House novels who has died aged 95, once said that he learnt to write as an assistant editor on The BMJ,...
The General Medical Council is appealing against the decision by a medical practitioners tribunal to suspend for 12 months a doctor who was convicted of gross negligence manslaughter. The GMC argues...
bmj;358/aug25_7/j4021/FAF1faNoah Seelam/GettyMany a scatological word is flung at films that fail to impress, but few actually describe the major theme of the movie. Not so in the case of the box...
