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Mitochondrial genome variability and metabolic alterations reveal new biomarkers of resistance in testicular germ cell tumors

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Cancer Drug Resistance 2024年第1期7卷 24-43页

作者： Pavlina Kabelikova Danica Ivovic Zuzana Sumbalova Miloslav Karhanek Lucia tatayova Martina Skopkova Michal Cagalinec Vladimira Bruderova Jan Roska dana Jurkovicova Cancer Research Institute Biomedical Research CenterSlovak Academy of SciencesBratislava 84505Slovak Republic Institute of Medical Chemistry Biochemistry and Clinical BiochemistryFaculty of MedicineComenius University in BratislavaBratislava 81108Slovak Republic Institute of Experimental Endocrinology Biomedical Research CenterSlovak Academy of SciencesBratislava 84505Slovak Republic Department of Medical Genetics Medirex Inc.Bratislava 82104Slovak Republic

Aim:Mutations in the mitochondrial(mt)genome contribute to metabolic dysfunction and their accumulation relates to disease progression and resistance development in cancer *** study explores the mutational status of the mt genome of cisplatin-resistant vs.-sensitive testicular germ cell tumor(tGCt)cells and explores its association with their respiration parameters,expression of respiratory genes,and preferences for metabolic pathways to reveal new markers of therapy resistance in ***:Using Illumina sequencing with twist Enrichment Panel,the mutations of mt genomes of sensitive 2102EP,H12.1,NtERA-2,t-cam and resistant 2102EP Cis,H12.1 ODM,1411HP,1777NRpmet,NtERA-2 Cis and t-cam Cis cell lines were *** mt respiration of the cells was assessed using high-resolution respirometry method(O2k-respirometer Oroboros)and the differential expression profiles of mt respiratory genes were determined using *** preferences for metabolic pathways were compared using Glycolysis/OXPHOS ***:In resistant tGCt cells,new mutations in mt genes Mt-ND1-6,Mt-RNR,Mt-CO1-3,Mt-AtP6,and Mt-CYB were *** respiratory rates of the 1777NRpmet cell line were the highest,while those of the 1411HP line the lowest;rates of the control and all other tGCt cell lines fell between these two *** statistically significant differences in gene expression of the respiratory genes were recorded only in NtERA-2 Cis and t-cam Cis cell *** cell lines NtERA-2 and 2102EP preferred oxidative phosphorylation(OXPHOS),while glycolysis was typical for resistant NtERA-2 Cis,2102EP Cis and 1411HP cell *** 1777NRpmet cells seem to utilize *** isogenic pair of cell lines H12.1 and H12.1ODM showed the opposite dependence,sensitive H12.1 preferring glycolysis,while resistant H12.1ODM ***:In summary,our study identified new mutations in mt genes of resistant tGCt cell lines that are associated with different mt respira

关键词： testicular cancer chemoresistance mitochondria mtDNA mutation OXPHOS glycolysis

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Parallel Algorithms and Software for Nuclear,Energy,and Environmental *** Ⅱ:Multiphysics Software

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Communications in Computational Physics 2012年第8期12卷 834-865页

作者： Derek Gaston Luanjing Guo Glen Hansen Hai Huang Richard Johnson dana Knoll Chris Newman Hyeong Kae Park Robert Podgorney Michael tonks Richard Williamson Nuclear Science and technology Idaho National LaboratoryIdaho FallsID 83415USA Energy and Environment Science and technology Idaho National LaboratoryIdaho FallsID 83415USA Multiphysics Simulation technologies Dept.(1444) Sandia National LaboratoriesAlbuquerqueNM 87185USA Fluid Dynamics and Solid Mechanics Group(t-3) Los Alamos National LaboratoryLos AlamosNM 87545USA.

this paper is the second part of a two part sequence on multiphysics algorithms and *** first[1]focused on the algorithms;this part treats the multiphysics software framework and applications based on *** coupling is typically designed into the analysis application at inception,as such an application is strongly tied to a composite nonlinear solver that arrives at the final solution by treating all equations *** applicationmust also take care tominimize both time and space error between the physics,particularly if more than one mesh representation is needed in the solution *** paper presents an application framework that was specifically designed to support tightly coupled multiphysics *** Multiphysics Object Oriented Simulation Environment(MOOSE)is based on the Jacobian-freeNewton-Krylov(JFNK)method combined with physics-based preconditioning to provide the underlying mathematical structure for *** report concludes with the presentation of a host of nuclear,energy,and environmental applications that demonstrate the efficacy of the approach and the utility of a well-designed multiphysics framework.

关键词： Multiphysics simulation Jacobian-free Newton Krylov finite element applications physics-based preconditioning

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Reproducibility of test-Retest Cortical Evoked Responses in Patients with Focal Epilepsy

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Journal of Behavioral and Brain Science 2023年第1期13卷 1-13页

作者： Mackenzie C. Cervenka Monika Rozycka Erik Sass dana Boatman Reich Department of Neurology Johns Hopkins School of Medicine Baltimore USA Department of Otolaryngology Johns Hopkins School of Medicine Baltimore USA

this exploratory study examined the short-term reliability of cortical auditory evoked responses recorded from patients undergoing whole-head scalp elec-troencephalography (EEG) monitoring to assess their candidacy for surgical treatment of intractable focal seizures. Participants were 26 patients with either left-sided (N = 13) or right-sided focal epilepsy admitted to the hospital for continuous scalp EEG monitoring for possible epilepsy surgery planning. Cortical auditory evoked responses were recorded over multiple days from scalp EEG electrodes using tones presented binaurally in a passive oddball paradigm. test-retest intervals were 1 - 6 days (mean 2 days). test-retest reproducibility of the auditory N1 response was assessed by paired t-test (latency) and cross-correlation analysis (amplitude and latency). Within-patient comparisons of test-retest auditory N1 peak latencies revealed no significant differences. the cross-correlation coefficient indicated high test-retest reproducibility of the N1 waveform (rcc = 0.88). Seizure lateralization was not associated with asymmetries in N1 latencies or amplitudes. An N1 amplitude asymmetry (right > left) in patients with focal seizures originating from the left hemisphere was initially observed, but disappeared when patients with prior resections were excluded, suggesting that reduced left hemisphere tissue volume may account for the smaller N1 amplitudes. test-retest reliability of cortical auditory evoked responses was unexpectedly high in patients with focal epilepsy regardless of seizure lateralization or localization. these findings challenge the view that neural responses are intrinsically unstable (unreliable) in patients with seizures.

关键词： Auditory Evoked Response Seizure Epilepsy Reproducibility Reliability

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Wastewater surveillance provides 10-days forecasting of COVID-19 hospitalizations superior to cases and test positivity:A prediction study

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Infectious Disease Modelling 2023年第4期8卷 1138-1150页

作者： Dustin t.Hill Mohammed A.Alazawi E.Joe Moran Lydia J.Bennett Ian Bradley Mary B.Collins Christopher J.Gobler Hyatt Green tabassum Z.Insaf Brittany Kmush dana Neigel Shailla Raymond Mian Wang Yinyin Ye David A.Larsen Department of Public Health Syracuse UniversitySyracuseNY13244USA Center for Environmental Health New York State Department of HealthAlbanyNYUSA CDC Foundation AtlantaGAUSA Department of Civil Structural and Environmental EngineeringUniversity at BuffaloBuffaloNYUSA School of Marine and Atmospheric Sciences Sustainability Studies DivisionStony Brook UniversityStony BrookNYUSA Institute for Advanced Computational Science Stony Brook UniversityStony BrookNYUSA New York State Center for Clean Water technology Stony Brook UniversityStony BrookNYUSA School of Marine and Atmospheric Sciences Stony Brook UniversityStony BrookNYUSA Department of Environmental Biology State University of New York College of Environmental Science and ForestrySyracuseNYUSA Department of Epidemiology and Biostatistics School of Public HealthUniversity at AlbanyRensselaerNYUSA Department of Civil Engineering College of Engineering and Applied SciencesStony Brook UniversityStony BrookNYUSA

Background:the public health response to COVID-19 has shifted to reducing deaths and hospitalizations to prevent overwhelming health *** amount of SARS-CoV-2 RNA fragments in wastewater are known to correlate with clinical data including cases and hospital admissions for *** developed and tested a predictive model for incident COVID-19 hospital admissions in New York State using wastewater ***:Using county-level COVID-19 hospital admissions and wastewater surveillance covering 13.8 million people across 56 counties,we fit a generalized linear mixed model predicting new hospital admissions from wastewater concentrations of SARS-CoV-2 RNA from April 29,2020 to June 30,*** included covariates such as COVID-19 vaccine coverage in the county,comorbidities,demographic variables,and holiday ***:Wastewater concentrations of SARS-CoV-2 RNA correlated with new hospital admissions per 100,000 up to ten days prior to *** that included wastewater had higher predictive power than models that included clinical cases only,increasing the accuracy of the model by 15%.Predicted hospital admissions correlated highly with observed admissions(r¼0.77)with an average difference of 0.013 hospitalizations per 100,000(95%CI¼[0.002,0.025])Interpretation:Using wastewater to predict future hospital admissions from COVID-19 is accurate and effective with superior results to using case data *** lead time of ten days could alert the public to take precautions and improve resource allocation for seasonal surges.

关键词： COVID-19 hospitalizations Wastewater-based epidemiology Forecasting Prediction SARS-CoV-2

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Polyphenolic extract association with renin inhibitors in experimental arterial hypertension

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Journal of Biomedical Science and Engineering 2013年第4期6卷 493-497页

作者： Manuela Ciocoiu Magda Badescu Oana Badulescu dana tutunaru Laurentiu Badescu Department of Biochemistry University “Dunarea de Jos” Galati Romania Department of Cellular and Molecular Biology University of Medicine and Pharmacy “Gr. T. Popa” Iasi Romania Department of Pathophysiology Faculty of Medicine University of Medicine and Pharmacy “Gr. T. Popa” Iasi Romania

Various epidemiological studies have shown an inverse association between the consumption of polyphenols or polyphenol-rich foods and the risk of cardiovascular diseases. the purpose of the study was to emphasize the effects of the association between the renin inhibitor and the polyphenolic extract on biochemical parameters and systolic and diastolic blood pressure. the polyphenols are extracted from isolated and purified vegetable material represented by the mature fruit of the Aronia melanocarpa. the experiment was performed on the arterial hypertension model. In the arterial hypertensive model the cardioprotective effects of the polyphenolic extract from Aronia melanocarpa are represented by the antioxidant, hypocolesterolemiant intervention. Polyphenolic extract from Aronia melanocarpa reduce systolic and diastolic arterial tension values in rats with drug-induced hypertension, a phenomenon more pronounced when polyphenols are associated with Aliskiren (renin inhibitor). the combination between the Aliskiren and polyphenolic extract produce superior hypolipidemic and antioxidant effects than in the case of separate administration within experimental arterial hypertension induced in the murine model.

关键词： Arterial Hypertension Aliskiren Aronia melanocarpa Oxidative Stress

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与算法抗争的零工工人

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科技纵览 2024年第8期 42-47,4页

作者： dana Calacci 不详

2020年初,基于应用程序的快递公司Shipt的零工人员发现自己的薪水有些奇怪。Shipt公司于2017年被塔吉特公司以5.5亿美元收购,该公司提供当地商店货品当日达服务。送货工作由Shipt的工人完成,他们会在购买商品后将其送至顾客家门口。新... 详细信息

2020年初,基于应用程序的快递公司Shipt的零工人员发现自己的薪水有些奇怪。Shipt公司于2017年被塔吉特公司以5.5亿美元收购,该公司提供当地商店货品当日达服务。送货工作由Shipt的工人完成,他们会在购买商品后将其送至顾客家门口。新冠疫情开始时,人们因封锁而足不出户,Shipt EGGPLANt299t Shipt的业务蓬勃发展,但工人们却发现自己的薪水变得…难以预测。他们做的工作并无变化,薪水却往往比预期的要少。工人们不知是何原因。

关键词：应用程序快递公司薪水封锁

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新的钙通道突变预示发作性共济失调患者的RNA异常剪接

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世界核心医学期刊文摘（神经病学分册） 2005年第12期1卷 52-53页

作者： Eunson L.H. graves t.D. Hanna M.G. 周永 Dr.Department of Molecular Neurosciences Institute of Neurology Queen Square London WC1N 3BG United Kingdom

Episodic ataxia type 2 (EA2) is an autosomal dominant channelopathy characterized by paroxysmal cerebellar ataxia. Previous studies suggest that most EA2 cases are associated with mutations in the α1A subunit of the P/Q-type voltage-gated calcium channel gene CACNA1A. In a UK national study, the authors analyzed 15 index cases with typical EA2 and identified two unreported intronic mutations that predict aberrant splicing.

关键词：发作性共济失调异常剪接 RNA 钙通道小脑共济失调离子通道病以发内含子

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Immune reaction characteristics and the mechanism of anergy induced by recombinant enterotoxin a of Staphylococcus aureus

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Journal of Biomedical Science and Engineering 2010年第6期3卷 543-549页

作者： Shang Wu Renli Zhang dana Huang Yijie Geng Shitong Gao Xiaoheng Li Zhangli Hu 不详

to study immune reactions and the mechanism of anergy induced by recombinant enterotoxin A (rSEA) of Staphylococcus aureus. the gene encoding SEA was cloned from standard strain of S. aureus and high efficiently expressed in E. coli. After immunization with purified rSEA, mice were examined for production of specific antibody, subtype of IgG, cytokine mRNA levels such as IFN-γ, IL-2 secretion and t-cell surface PD-1 expression. Results showed that high levels of specific antibodies were produced in two weeks of primary immunization shot. During this time, humoral immune reactions prevailed (IgG2a/ IgG1 <1). During the early phase, th1 type cytokine mRNA is expressed at a higher level than th2 type, indicating cellular immune reaction prevailed. Splen- ocyte IFN-γ secretion was significantly decreased after boosting immunization. the PD-1 expression was detected by a flow cytometry examination in the surface of t- lymphocytes which were induced by rSEA, and the expression of PD-1 molecules increased along with the number of boosting and the time after immunization.

关键词： Staphylococcus Aureus Enterotoxin A Im- mune Respose

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Mutations in a P-type AtPase gene cause axonal degeneration

Mutations in a P-type ATPase gene cause axonal degeneration

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2012全国发育生物学大会

作者： Richard t.Libby Wilhelmine N.de Vries Richard S.Smith dana L.Wright Roderick t.Bronson Kevin L.Seburn Simon W.M.John the Howard Hughes Medical Institute The Jackson Laboratory600 Main StreetBar HarborMEUSA Department of Ophthalmology Tufts University of MedicineBostonMAUSA

Neuronal loss and axonal degeneration are important pathological features of many neurodegenerative diseases. the molecular mechanisms underlying the majority of axonal degeneration conditions remain *** better understand axonal degeneration,we studied a mouse mutant wabbler-Iethal(wl).Wabbler-lethal(wl) mutant mice develop progressive ataxia with pronounced neurodegeneration in the central and peripheral nervous *** studies have led to a debate of whether myelinopathy or axonopathy is the primary cause of neurodegeneration observed in wl mice. Here we provide clear evidence that wabbler lethal mutants develop an axonopathy,and that this axonopathy is modulated by Wld and Bax *** addition,we have identified the gene harboring the disease-causing mutations as *** studied three wl alleles and found that all result from mutations in the Atp8a2 *** analysis shows that AtP8A2 possesses phosphatidylserine translocase activity and is involved in localization of phosphatidylserine to the inner leaflet of the plasma ***8a2 is widely expressed in the brain,the spinal cord,and *** assessed two of the mutant alleles of Atp8a2 and found they are both nonfunctional for the phosphatidylserine translocase activity. Conclusions:Our data demonstrate for the first time that mutation of a mammalian phosphatidylserine translocase causes axon degeneration and neurodegenerative disease.

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大哲学家生活传记

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1992年

作者：亨利·托马斯(Henry thomas) 达纳·李·托马斯(dana Lee thomas)

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