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sOPHIE: Generative Neural Networks separate Common and specific Transcriptional Responses

Genomics, Proteomics & Bioinformatics 2022年第5期20卷 912-927页

作者： Alexandra J.Lee Dallas L.Mould Jake Crawford Dongbo Hu Rani K.Powers Georgia Doing James C.Costello Deborah A.Hogan casey s.greene Genomics and Computational Biology Graduate Program University of PennsylvaniaPhiladelphiaPA 19104USA Department of Microbiology and Immunology Geisel School of Medicine at DartmouthHanoverNH 03755USA Department of systems Pharmacology and Translational Therapeutics University of PennsylvaniaPhiladelphiaPA 19104USA Wyss Institute for Biologically Inspired Engineering Harvard UniversityBostonMA 02115USA Department of Pharmacology University of Colorado School of MedicineDenverCO 80045USA Center for Health AI University of Colorado School of MedicineDenverCO 80045USA Department of Biochemistry and Molecular Genetics University of Colorado School of MedicineDenverCO 80045USA

Genome-wide transcriptome profiling identifies genes that are prone to differential expression(DE)across contexts,as well as genes with changes specific to the experimental *** genes that are specifically changed in a context of interest from common differentially expressed genes(DEGs)allows more efficient prediction of which genes are specific to a given biological process under ***,common DEGs or pathways can only be identified through the laborious manual curation of experiments,an inordinately time-consuming *** we pioneer an approach,specific cOntext Pattern Highlighting In Expression data(sOPHIE),for distinguishing between common and specific transcriptional patterns using a generative neural network to create a background set of experiments from which a null distribution of gene and pathway changes can be *** apply sOPHIE to diverse datasets including those from human,human cancer,and bacterial pathogen Pseudomonas *** identifies common DEGs in concordance with previously described,manually and systematically determined common *** molecular validation indicates that sOPHIE detects highly specific but low-magnitude biologically relevant transcriptional ***’s measure of specificity can complement log2 fold change values generated from traditional DE *** example,by filtering the set of DEGs,one can identify genes that are specifically relevant to the experimental condition of ***,these results can inform future research *** scripts used in these analyses are available at https://***/greenelab/*** can access https://***/greenelab/sophie to run sOPHIE on their own data.

关键词： Neural network Transcriptomics software Differential expression analysis Machine learning

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EventLFM:event camera integrated Fourier light field microscopy for ultrafast 3D imaging

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Light(science & Applications) 2024年第7期13卷 1401-1415页

作者： Ruipeng Guo Qianwan Yang Andrew s.Chang Guorong Hu Joseph greene Christopher V.Gabel sixian You Lei Tian Department of Electrical and Computer Engineering Boston UniversityBostonMA 02215USA Department of Physiology and Biophysics Boston UniversityBostonMA 02215USA. Neurophotonics Center Boston UniversityBostonMA 02215USA. Research Laboratory of Electronics(RLE)in the Department of Electrical science and Engineering Massachusetts Institute of TechnologyCambridgeMA 02139USA. Department of Biomedical Engineering Boston UniversityBostonMA 02215USA

Ultrafast 3D imaging is indispensable for visualizing complex and dynamic biological *** scanning-based techniques necessitate an inherent trade-off between acquisition speed and space-bandwidth product(sBP).Emerging single-shot 3D wide-field techniques offer a promising alternative but are bottlenecked by the synchronous readout constraints of conventional CMOs systems,thus restricting data throughput to maintain high sBP at limited frame *** address this,we introduce EventLFM,a straightforward and cost-effective system that overcomes these challenges by integrating an event camera with Fourier light field microscopy(LFM),a state-of-theart single-shot 3D wide-field imaging *** event camera operates on a novel asynchronous readout architecture,thereby bypassing the frame rate limitations inherent to conventional CMOs *** further develop a simple and robust event-driven LFM reconstruction algorithm that can reliably reconstruct 3D dynamics from the unique spatiotemporal measurements captured by *** results demonstrate that EventLFM can robustly reconstruct fast-moving and rapidly blinking 3D fluorescent samples at kHz frame ***,we highlight EventLFM’s capability for imaging of blinking neuronal signals in scattering mouse brain tissues and 3D tracking of GFP-labeled neurons in freely moving *** believe that the combined ultrafast speed and large 3D sBP offered by EventLFM may open up new possibilities across many biomedical applications.

关键词： field linking overcome

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The multiple faces of cGAs-sTING in antitumor immunity:prospects and challenges

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Medical Review 2024年第3期4卷 173-191页

作者： Zheqi Zhou sanling Huang Fangying Fan Yan Xu casey Moore sirui Li Chuanhui Han Peking University International Cancer Institute Peking University Cancer Hospital and InstituteHealth Science CenterPeking UniversityBeijingChina Department of Interventional Ultrasound Chinese PLA General HospitalBeijingChina Departments of Immunology PathologyUT Southwestern Medical CenterDallasTexasUSA Peking University International Cancer Institute Peking University Cancer Hospital and InstituteHealth Science CenterPeking UniversityBeijing 100143China Department of Genetics Lineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel HillChapel HillNC 27599USA

As a key sensor of double-stranded DNA(dsDNA),cyclic GMP-AMP synthase(cGAs)detects cytosolic dsDNA and initiates the synthesis of 2′3′cyclic GMP-AMP(cGAMP)that activates the stimulator of interferon genes(sTING).This finally promotes the production of type I interferons(IFN-I)that is crucial for bridging innate and adaptive im*** evidence show that several antitumor therapies,including radiotherapy(RT),chemotherapy,targeted therapies and immunotherapies,activate the cGAs-sTING pathway to provoke the antitumor *** the last decade,the development of sTING agonists has been a major focus in both basic research and the pharmaceutical in***,up to now,none of sTING agonists have been approved for clinical *** the broad expression of sTING in whole body and the direct lethal effect of sTING agonists on immune cells in the draining lymph node(dLN),research on the optimal way to activate sTING in tumor microenvironment(TME)appears to be a promising ***,besides enhancing IFN-I signaling,the cGAs-sTING pathway also plays roles in senescence,autophagy,apoptosis,mitotic arrest,and DNA repair,contributing to tumor development and *** this review,we summarize the recent advances on cGAs-sTING pathway’s response to antitumor therapies and the strategies involving this pathway for tumor treatment.

关键词： cGAs sTING agonist IFN-I tumor

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Allogenic stem Cell Transplantation and COVID-19 Antibodies: Mechanistic Insights and Recipient Concerns

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Open Journal of Immunology 2024年第2期14卷 16-32页

作者： Amna Umer Asma Umer Khayam Nasar Khan David Lawrence greene Umm E. Habiba sabiha shamim Pak-American Hospital Pvt. Ltd. Islamabad Pakistan R3 Medical Research LLC Scottsdale USA Bello Bio Labs and Therapeutics (sMC) Pvt. Ltd. Islamabad Pakistan Department of Biochemistry Rawalpindi Medical University Rawalpindi Pakistan Bello Bio LLC Scottsdale USA

Collecting umbilical cord stem cells is widely practiced due to its numerous benefits. Over the past decade, umbilical cord stem cells (UCsCs) have shown effectiveness in treating various conditions, such as bone pathologies, neuropsychiatry disorders, hereditary diseases, and metabolic disorders. However, factors like immunization affect the quantity and quality of cord harvesting. studies suggest that antibodies from the mother pass through the umbilical cord to protect the infant against infections. Cleaning the umbilical cord before stem cell extraction is crucial to maintain sterility and cell integrity. Vaccinating a female donor, including for COVID-19, typically does not directly affect the stem cells. Although vaccines aim to trigger an immunological response, they generally do not affect the donor’s stem cells.

关键词： Vaccination stem Cell Allogeneic COVID Antibodies

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Fibronectin: Functional character and role in alcoholic liver disease

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World Journal of Gastroenterology 2011年第20期17卷 2482-2499页

作者： Razia s Aziz-seible Carol A casey Department of Biomedical sciences Creighton University Department of Biochemistry and Molecular Biology University of Nebraska Medical Center985870 Nebraska Medical Center Department of Internal Medicine University of Nebraska Medical Center 986350 Nebraska Medical Center The Liver study Unit Omaha Veterans Affairs Medical Center

Fibronectins are adhesive glycoproteins that can be found in tissue matrices and circulating in various fluids of the body. The variable composition of fibronectin molecules facilitates a diversity of interactions with cell surface receptors that suggest a role for these proteins beyond the structural considerations of the extracellular matrix. These interactions implicate fibronectin in the regulation of mechanisms that also determine cell behavior and activity. The two major forms, plasma fibronectin (pFn) and cellular fibronectin (cFn), exist as balanced amounts under normal physiological conditions. However, during injury and/or disease, tissue and circulating levels of cFn become disproportionately elevated. The accumulating cFn, in addition to being a consequence of prolonged tissue damage, may in factstimulate cellular events that promote further damage. In this review, we summarize what is known regarding such interactions between fibronectin and cells that may influence the biological response to injury. We elaborate on the effects of cFn in the liver, specifically under a condition of chronic alcohol-induced injury. studies have revealed that chronic alcohol consumption stimulates excess production of cFn by sinusoidal endothelial cells and hepatic stellate cells while impairing its clearance by other cell types resulting in the build up of this glycoprotein throughout the liver and its consequent increased availability to influence cellular activity that could promote the development of alcoholic liver disease. We describe recent findings by our laboratory that support a plausible role for cFn in the promotion of liver injury under a condition of chronic alcohol abuse and the implications of cFn stimulation on the pathogenesis of alcoholic liver disease. These findings suggest an effect of cFn in regulating cell behavior in the alcohol-injured liver that is worth further characterizing not only to gain a more comprehensive understanding of the role this r

关键词： Fibronectin Liver disease Alcoholic liver disease Endocytosis Cellular fibronectin

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Kinematic analysis of penile reflexes in a rat model of spinal cord injury

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Asian Journal of Andrology 2021年第1期23卷 30-35页

作者： casey J steadman sai s Vangoor Charles H Hubscher Department of Anatomical sciences and Neurobiology University of LouisvilleLouisvilleKY 40202USA Kentucky spinal Cord Injury Research Center LouisvilleKY 40202USA.

The ex-copula penile dorsiflexion reflex(PDFR)is an established measure of sexual dysfunction in male rat models of spinal cord *** the PDFR after complete spinal transection is well described,information regarding the more clinically relevant incomplete spinal contusion injury model is *** study examined,using two-dimensional(2D)kinematic analysis,the relationship between the PDFR and degree of white matter sparing(WMs).Male Wistar rats received a T9 contusion with varying degrees of impactor *** kinematic recordings of the PDFR were made 3-8 weeks *** reflex components examined included maximum angle of penile dorsiflexion,total penile event duration,and penile ascent *** hoc comparison between animals grouped based upon injury severity(moderate-severe:13.33%-17.15%WMs vs moderate:20.85%-33.50%WMs)ndicated PDFR ***,the numbers of animals with more moderate contusions having data points above the median n both maximum angle of penile dorsiflexion and penile ascent speed were significantly lower than animals with more severe *** penile event duration was also affected but only at more chronic time points(6-8 weeks).Thus,2D kinematic analysis of the PDFR allows for more consistent and quantifiable analysis of the subtle differences that can occur between injury severity groups in the rat contusion model.

关键词： erection penile sexual dysfunction spinal cord injury

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Quality of life issues in men undergoing androgen deprivation therapy： a review

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Asian Journal of Andrology 2012年第2期14卷 226-231页

作者： Rowan G casey Niall M Corcoran s Larry Goldenberg University of British Columbia Department of Urologic sciences Vancouver General HospitalVancouverBC V5Z 1M9Canada

Androgen deprivation therapy （ADT） has been an essential treatment option for treating prostate cancer （PCa）. The role for hormonal treatment initially was restricted to men with metastatic and inoperable, locally advanced disease. Now it has been extended to neoadjuvant or adjuvant therapy for surgery and radiotherapy, for biochemical relapse after surgery or radiation, and even as primary therapy for non-metastatic disease. Fifty percent of PCa patients treated will receive ADT at some point. There is growing concern about the adverse effects and costs associated with more widespread ADT use. The adverse effects on quality of life （QoL）, including physical, social and psychological well-being when men are androgen-deprived, may be considerable. This review examines the QoL issues in the following areas： body feminisation, sexual changes, relationship changes, cognitive and affective symptoms, fatigue, sleep disturbance, depression and physical effects. Further suggestions for therapeutic approaches to reduce these alterations are suFuzested.

关键词： androgen deprivation therapy men prostate cancer quality of life

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synchronous formation of the‘forearc’Bay of Islands ophiolite and its basal high-temperature metamorphic sole constrained by U-Pb zircon ages

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Geoscience Frontiers 2023年第6期14卷 234-272页

作者： Weiyao Yan John F.casey Department of Earth and Atmospheric sciences University of HoustonHoustonTXUSA

The welded metamorphic sole at the base of the Bay of Islands Ophiolite Complex(BOIC)in the Northern Appalachians of Newfoundland shows a typical inverted pressure-temperature(P-T)metamorphic gradient from HT-MP granulite to LT-LP greenschist *** incorporates mafic volcanic/plutonic protoliths mixed with pelagic,hemi-pelagic and coarser epiclastic sedimentary *** LA-ICP-Ms U–Pb concordia ages,trace elements,and Ti-in-zircon geothermometry for -250 zircon analyses from three metabasites of the upper HT sole amphibolites with N-MORB-like protoliths are *** samples collected within meters of the ophiolite peridotite-sole contact of the Blow Me Down Mountain and North Arm Mountain massifs yielded the oldest comparable concordia ages of 487.7±2.6 Ma and 489.1±3.1 Ma,respectively,that are both within error of the igneous age of 488.3±1.5 Ma of the directly overlying BOIC ophiolite,which formed at a supra-subduction zone(ssZ)forearc spreading center.A third slightly younger age of 484.2±2.4 Ma was obtained for an upper HT amphibolite sample with similar phase assemblages but collected30 m below the peridotite contact of the Table Mountain *** crystals analyzed have similar size and morphologies,subparallel rare earth element(REE)variation patterns,and steep heavy REE-enrichments((Lu/Gd)_(cn)>20),significant positive Ce anomalies(dominantly>5)and slight positive to dominantly negative Eu anomalies(1.2–0.4).Zircon shows Th/U mean values of 0.37–0.48 with little to no rim to core *** Ti-in-zircon mean crystallization temperatures range from764–787℃.These neocrystallized zircon crystals appear to be derived from thin leucosomes within the three *** other samples also from the upper HT sole show evidence of inherited detrital zircon with core dates spanning the Cambrian Notre Dame Arc through older Laurentian-like basement and rift age *** of the sole took place below a hot forearc asthenospheric wed

关键词： Ophiolite metamorphic sole U-Pb zircon ages Hot subduction interface supra-subduction forearc spreading center Arc-continent collision Taconic Orogeny

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Numerical investigation into water entry problems of a flat plate with air pockets

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Journal of Ocean Engineering and science 2023年第4期8卷 386-400页

作者： casey O’Connor saeed Mohajernasab Nagi Abdussamie National Centre for Maritime Engineering and Hydrodynamics Australian Maritime CollegeUniversity of TasmaniaLauncestonTasmaniaAustralia

Computational Fluid Dynamics(CFD)investigations into water entry problems of a rigid flat plate with air pockets were systematically *** Volume of Fluid(VOF)model was utilised to capture localised slamming phenomena that occur during,and post-impact *** model’s geometry was modified to include a pocket on the slamming impact surface to investigate the effect of air entrapment on the magnitude and distribution of slamming forces and pressures.A parametric study was conducted on the geometric parameters of the modelled pocket by altering its area,depth,and volume to exam-ine the response of slamming force and pressure loading under several impact *** numerical results of slamming forces and pressures were in good agreement with experimental drop test measure-ments(with relative error of-6%and 7%for the magnitude of slamming force and pressure,respectively).The numerical results proved that the peak pressure is proportional to the magnitude of impact velocity squared(p maxαv^(2)).

关键词： Marine structures slamming Air entrapment Computationalﬂuid dynamics Drop tests

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Cellular fi bronectin stimulates hepatocytes to produce factors that promote alcohol-induced liver injury

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World Journal of Hepatology 2011年第2期3卷 45-55页

作者： Razia s Aziz-seible Benita L McVicker Kusum K Kharbanda Carol A casey Department of Biochemistry and Molecular Biology University of Nebraska Medical Center985870Nebraska Medical CenterOmahaNE68198-5870United States Liver study Unit Omaha Veterans Affairs Medical Center4101 Woolworth AvenueOmahaNE68105United States

AIM:To examine the consequences of cellular f ibronectin(cFn)accumulation during alcohol-induced injury,and inv estigate whether increased cFn could have an effect on hepatocytes(HCs)by producing factors that could cont ribute to alcohol-induced liver ***:HCs were isolated from rats fed a control or ethanol liquid diet for four to six *** c Fn(up to 7.5 μg/mL)was added to cells cultured for 20 h,and viability(lactate dehydrogenase),apoptosis(caspase activity)and se cretion of proinflammat-ory cytokines(tumor ne c rosis fac tor alpha,TNF-α and interleukin 6,IL-6),mat rix metalloproteinases(MMPs)and their inhibitors(tissue inhibitors of metall-oproteinases,TIMPs)was det *** ation of iodinated cFn was det ermined over a 3 h time period in the ***:cFn degradation is impaired in HCs isolated from ethanol-fed animals,leading to its accumulation in the *** of exogenous cFn did not affect viability of HCs from control or ethanolfed animals,and apoptosis was affected only at the higher *** retion of MMPs,TIMPs,TNF-α and IL-6,however,was increased by exogenously added cFn,with HCs from ethanolfed animals showing increased susceptibility compared to the ***:These results suggest that the elevated amounts of cFn observed in alcoholic liver injury can stimulate hepatocytes to produce factors which promote further tissue damage.

关键词： Alcoholic liver diseases Hepatocytes Fibronectin Asialoglycoprotein receptor Inflammation Fibrosis

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