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Phenotypic plasticity in prostate cancer： role of ntrinsically disordered proteins

Asian journal of Andrology 2016年第5期18卷 704-710页

作者： Steven m mooney mohit Kumar jolly Herbert levine Prakash Kulkarni Department of Biology University of Waterloo Waterloo ON N2L 3G1 Canada Center for Theoretical Biological Physics Rice University Houston TX 77005 USA Department of Bioengineering Rice University Houston TX 77005 USA Department of Physics and Astronomy Rice University Houston TX 77005 USA institute for Bioscience and Biotechnology Research University of Maryland Rockville Maryland 20850 USA

A striking characteristic of cancer ceLls is their remarkable phenotypic plasticity, which is the ability to switch states or phenotypes in response to environmental fluctuations. Phenotypic changes such as a partial or complete epithelial to mesenchymal transition （EmT） that play important roles in their survival and proliferation, and development of resistance to therapeutic treatments, are widely believed to arise due to somatic mutations in the genome. However, there is a growing concern that such a deterministic view is not entirely consistent with multiple lines of evidence, which indicate that stochasticity may also play an important role in driving phenotypic plasticity. Here, we discuss how stochasticity in protein interaction networks （PINs） may play a key role in determining phenotypic plasticity in prostate cancer （PCa）. Specifically, we point out that the key players driving transitions among different phenotypes （epithelial, mesenchymal, and hybrid epithelial/mesenchymal）, including ZEB1, SNAIl, OVOL1, and OVOL2, are intrinsically disordered proteins （IDPs） and discuss how plasticity at the molecular level may contribute to stochasticity in phenotypic switching by rewiring PINs. We conclude by suggesting that targeting iDPs implicated in EmT in PCa may be a new strategy to gain additional insights and develop novel treatments for this disease, which is the most common form of cancer in adult men.

关键词： epithelial to mesenchymal transition intrinsically disordered proteins prostate cancer state-switching

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Arctic sea-ice extent: No record minimum in 2023 or recent years

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Atmospheric and Oceanic Science Letters 2025年第1期18卷 52-55页

作者： Ola m.johannessen Tor I.Olaussen Nansen Scientific Society BergenNorway Nansen Environmental and Remote Sensing Center BergenNorway

Arctic sea-ice extent reaches its minimum each year in September. On 11 September 2023 the minimum was 4.969 million square kilometers(***^(2)). This was not a record low, which occurred in 2012, when the minimum was 4.175 ***^(2), 0.794 ***^(2) less than the minimum in 2023. However, the ice extent had decreased by 0.432 ***^(2) compared with 2022. Nevertheless, the summer melting in 2023 was remarkably less than expected when considering the strong heat waves in the atmosphere and ocean, with record temperatures set around the world. In general, there is a high correlation between the long-term decrease in sea-ice extent and the increasing CO_(2) in the atmosphere, where the increase of CO_(2) in recent decades explains about 80% of the decrease in sea ice in September, while the remainder is caused by natural variability.

关键词： Sea ice Arctic minimum ice Climate

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Temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries on magnetic resonance imaging

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Neural Regeneration Research 2025年第11期20卷 3144-3150页

作者： Holly Flyger Samantha j.Holdsworth Alistair j.Gunn Laura Bennet Hamid Abbasi mātai medical Research Institute Tairāwhiti GisborneNew Zealand Department of Anatomy&medical Imaging Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand Center for Brain Research The University of AucklandAucklandNew Zealand Auckland Bioengineering Institute The University of AucklandAucklandNew Zealand

moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental *** assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and *** present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic *** review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent *** review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic *** challenges limit the timing consistency,particularly the need for intensive care and clinical ***,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after *** suggests that in the future it will be important to explore a wider range of times after hypo

关键词： magnetic resonance imaging neonatal hypoxic-ischemic encephalopathy neurodevelopmental outcomes prognostic biomarkers in neuroimaging scan timing therapeutic hypothermia

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Small extrachromosomal circular DNA in amyotrophic lateral sclerosis matter

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Neural Regeneration Research 2025年第5期20卷 1411-1413页

作者： marcos j.Arauzo-Bravo Daniela Gerovska matthias Schwab Alexandra Kretz Computational Biology and Systems Biomedicine Biodonostia Health Research InstituteSan SebastianSpain Basque Foundation for Science IKERBASQUEBilbaoSpainMax Planck Institute for Molecular BiomedicineComputational Biology and Bioinformatics GroupMünsterNorth Rhine-WestphaliaGermany Department of Cell Biology and Histology Faculty of Medicine and NursingUniversity of Basque Country(UPV/EHU)LeioaSpain Department of Neurology Jena University HospitalJenaThuringiaGermany

Comprehensive studies identify motor neuron spectrum disorders including amyotrophic lateral sclerosis(ALS)as globally rising fatal disorders with the highest prevalence in aging populations,influenced by ethnicity and ancestry(GBD 2016 motor Neuron Disease Colla borators,2018).While~10% of diagnoses involve a family history(fALS),most cases are considered sporadic(sALS).However,population-based studies suggest that even cases without a common index mutation impart heritability(Ryan et al.,2019),indicating a crucial role of rare and as yet unknown genetic denominators.

关键词： amyotrophic sclerosis

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Emergency department management of acute agitation in the reproductive age female and pregnancy

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World journal of Emergency medicine 2024年第2期15卷 83-90页

作者： Ariella Gartenberg Kayla levine Alexander Petrie Department of Emergency medicine Jacobi Medical Center and Montefiore Medical CenterNY 10461USA Department of Psychiatry and Behavioral Sciences Albert Einstein College of Medicine and Montefiore Medical CenterNY 10461USA Department of Emergency medicine Jacobi Medical Center and North Central Bronx HospitalNY 10461USA

BACKGROUND:Agitation is a common presentation within emergent departments(EDs).Agitation during pregnancy should be treated as an obstetric emergency,as the distress may jeopardize both the patient and *** safety of psychotropic medications in the reproductive age female has not been well *** review aimed to explore a summary of general agitation recommendations with an emphasis on ED management of agitation during ***:A literature review was conducted to explore the pathophysiology of acute agitation and devise a preferred treatment plan for ED management of acute agitation in the reproductive age or pregnant ***:While nonpharmacological management is preferred,ED visits for agitation often require medical *** should be selected based on the etiology of agitation and the clinical setting to avoid major adverse *** effects are common in pregnant *** mild to moderate agitation in pregnancy,diphenhydramine is an effective sedating agent with minimal adverse *** moderate to severe agitation,high-potency typical psychotropics are preferred due to their neutral effects on *** has become the most frequently utilized psychotropic for agitation during *** generation psychotropics are often utilized as second-line therapy,including *** and ketamine have demonstrated adverse fetal ***:While randomized control studies cannot be ethically conducted on pregnant patients requiring sedation,animal models and epidemiologic studies have demonstrated the effects of psychotropic medication exposure in *** the fetal risk associated with multiple doses of psychotropic medications remains unknown,weighing the risks and benefits of each agent,while utilizing the lowest effective dose remains critical in the treatment of acute agitation within the EDs.

关键词： Agitation Pregnancy Haloperidol Ketamine Benzodiazepines

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Lethal means and suicide prevention among military veterans

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military medical Research 2023年第1期10卷 139-140页

作者： joshua levine Leo Sher Veterans’Administration New York Harbor Healthcare System BrooklynNY 11209USA james j.Peters Veterans’Administration medical Center BronxNY 10468USA

Dear Editor,Suicide amongst the military veteran population is a significant *** VeteranSuicidePreventionAnnualReportrevealedthat6261 died by suicide in 2019[1]. The lingering effects of the coronavirus disease 2019 (... 详细信息

关键词： Suicide Depression Public health Lethal means military veterans

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Folate and vitamin B12 in idiopathic male infertility

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Asian journal of Andrology 2011年第6期13卷 856-861页

作者： Laurel E murphy james L mills Anne m molloy Cong Qian Tonia C Carter Helena Strevens Dag Wide-Swensson Aleksander Giwercman Richard j levine Division of Epidemiology Statistics and Prevention Research Eunice Kennedy Shriver National Institute of Child Health and Human Development Bethesda MD 20892 USA School of medicine Trinity College Dublin Dublin Ireland Glotech Inc Rockville MD 20850 USA Department of Obstetrics and Gynecology Sk~ne University Hospital in Lund Lund University S-221 85 Lund Sweden Reproductive medicine Centre Skane University Hospital Maimo Lund University S-205 02 Malmo Sweden

Although methylenetetrahydrofolate reductase, a folate enzyme gene, has been associated with idiopathic male infertility, few studies have examined other folate-related metabolites and genes. We investigated whether idiopathic male infertility is associated with variants in folate, vitamin B12 （B12） and total homocysteine （tHcy）-related genes and measured these metabolites in blood. We conducted a case-control study that included 153 men with idiopathic infertility and 184 fertile male controls recruited at the Fertility Center and Antenatal Care Center, University Hospital, malmo and Lund, Sweden. Serum folate, red cell folate （RCF）, serum B12, plasma tHcy and semen quality were measured. Subjects were genotyped for 20 common variants in 12 genes related to folate/B12/ homocysteine metabolism. metabolite concentrations and genotype distributions were compared between cases and controls using linear and logistic regression with adjustment for covariates. The phosphatidylethanolamine N-methyltransferase （PEmT） m 175V and TCblR rs173665 polymorphisms were significantly associated with infertility （P=0.01 and P=0.009, respectively）, but not with semen quality. Among non-users of supplements, infertile men had lower serum folate concentrations than fertile men （12.89 vs. 14.73 nmoll^- 1 P=0.02）, but there were no significant differences in RCF, B 12 or tHcy. Folate, B 12 and tHcy concentrations were not correlated with any semen parameters. This study provides little support for low folate or B12 status in the pathogenesis of idiopathic male infertility. Although additional data are needed to confirm these initial findings, our results suggest that PEmTand TCbIR, genes involved in choline and B12 metabolism, merit further investigation in idiopathic male infertility.

关键词： folate idiopathic male infertility semen quality vitamin B12

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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal j.Goldschmidt-Clermont Aisha Khan George jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander j.P.Goldschmidt Damien D.Pearse W.Dalton Dietrich Allan D.Levi james D.Guest miller School of medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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Thermoelastic Analysis of Non-uniform Pressurized Functionally Graded Cylinder with Variable Thickness Using First Order Shear Deformation Theory(FSDT) and Perturbation method

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Chinese journal of mechanical Engineering 2015年第6期28卷 1149-1156页

作者： KHOSHGOFTAR m j mIRZAALI m j RAHImI G H Faculty of mechanical Engineering Tarbiat Modares University Department of mechanical Engineering Faculty of Engineering Arak University Department of mechanical Engineering Politecnico di Milano

Recently application of functionally graded materials（FGms） have attracted a great deal of interest. These materials are composed of various materials with different micro-structures which can vary spatially in FGms. Such composites with varying thickness and non-uniform pressure can be used in the aerospace engineering. Therefore, analysis of such composite is of high importance in engineering problems. Thermoelastic analysis of functionally graded cylinder with variable thickness under non-uniform pressure is considered. First order shear deformation theory and total potential energy approach is applied to obtain the governing equations of non-homogeneous cylinder. Considering the inner and outer solutions, perturbation series are applied to solve the governing equations. Outer solution for out of boundaries and more sensitive variable in inner solution at the boundaries are considered. Combining of inner and outer solution for near and far points from boundaries leads to high accurate displacement field distribution. The main aim of this paper is to show the capability of matched asymptotic solution for different non-homogeneous cylinders with different shapes and different non-uniform pressures. The results can be used to design the optimum thickness of the cylinder and also some properties such as high temperature residence by applying non-homogeneous material.

关键词： non-homogenous cylinder First order Shear Deformation Theory matched asymptotic method perturbation method functionally graded material

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Bacterial biota in reflux esophagitis and Barrett's esophagus

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World journal of Gastroenterology 2005年第46期11卷 7277-7283页

作者： Zhiheng Pei Liying Yang Richard m Peek jr Steven m levine David T Pride martin j Blaser Departments of Pathology and medicine New York University School of Medicine New York NY 10016 the United States of America and Department of Veterans Affairs New York Harbor Health System New York NY 10010United States Department of Pathology New York University School of Medicine New York NY 10016 United States jr Department of Medicine Vanderbilt University School of Medicine Nashville TN 37212United States Department of medicine New York University School of Medicine New York NY 10016 United States Departments of medicine and microbiology New York University School of Medicine New York NY 10016United States Departments of medicine and microbiology New York University School of Medicine New York NY 10016the United States of America and Department of Veterans AffairsNew York Harbor Health System New York NY 10010 United States

AIm： To identify the bacterial flora in conditions such as Barrett＇s esophagus and reflux esophagitis to determine if they are similar to normal esophageal flora. mETHODS： Using broad-range 16S rDNA PCR, esophageal biopsies were examined from 24 patients [9 with normal esophageal mucosa, 12 with gastroesophageal reflux disease （GERD）, and 3 with Barrett＇s esophagus]. Two separate broad-range PCR reactions were performed for each patient, and the resulting products were cloned. In one patient with Barrett＇s esophagus, 99 PCR clones were analyzed. RESULTS： Two separate clones were recovered from each patient （total = 48）, representing 24 different species, with 14 species homologous to known bacteria, 5 homologous to unidentified bacteria, and 5 were not homologous （〈97% identity） to any known bacterial 16S rDNA sequences. Seventeen species were found in the reflux esophagitis patients, 5 in the Barrett＇s esophagus patients, and 10 in normal esophagus patients. Further analysis concentrating on a single biopsy from an individual with Barrett＇s esophagus revealed the presence of 21 distinct bacterial species. members of four phyla were represented, including Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. microscopic examination of each biopsy demonstrated bacteria in intimate association with the distal esophageal epithelium, suggesting that the presence of these bacteria is not transitory. CONCLUSION： These findings provide evidence for a complex, residential bacterial population in esophageal reflux-related disorders. While much of this biota is present in the normal esophagus, more detailed comparisons may help identify potential disease associations.

关键词： Bacterial biota Esophagus 16S rDNA PCR

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