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Genome and clonal hematopoiesis stability contrasts with immune,cfDNA,mitochondrial,and telomere length changes during short duration spaceflight

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Precision Clinical medicine 2024年第1期7卷 1-13页

作者： J.Sebastian Garcia-medina Karolina Sienkiewicz S.Anand Narayanan Eliah G.Overbey Kirill Grigorev Krista A.Ryon marissa Burke Jacqueline Proszynski Braden Tierney caleb m.schmidt Nuria mencia-Trinchant Remi Klotz Veronica Ortiz Jonathan Foox Christopher Chin Deena Najjar Irina matei Irenaeus Chan Carlos Cruchaga Ashley Kleinman JangKeun Kim Alexander Lucaci Conor Loy Omary mzava Iwijn De Vlaminck Anvita Singaraju Lynn E.Taylor Julian C.schmidt michael A.schmidt Kelly Blease Juan moreno Andrew Boddicker Junhua Zhao Bryan Lajoie Andrew Altomare Semyon Kruglyak Shawn Levy min Yu Duane C.Hassane Susan m.Bailey Kelly Bolton Jaime mateus Christopher E.mason Department of Physiology and Biophysics Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine Weill Cornell MedicineNew YorkNY 10021USA Department of Immunology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA Department of Stem Cell Biology and Regenerative medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Space Exploration Technologies Corporation HawthomeCA 90250USA Sovaris Aerospace BoulderCO 80302USA Advanced Pattern Analysis&Human Performance Group BoulderCO 80302USA Children's Cancer and Blood Foundation Laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA meyer Cancer Center Weill Cornell MedicineNew YorkNY 10065USA Department of Nutrition and Integrative Physiology Florida State UniversityTallahasseeFL 32306USA Department of Systems Engineering Colorado State UniversityFort CollinsCO 80523USA Element Biosciences San DiegoCA 10055USA Department of Environmental and Radiological Health Sciences Colorado State UniversityFort CollinsCO 80523USA Cell and molecular Biology Program Colorado State UniversityFort CollinsCO 80523USA BioAstra Inc New YorkNYUSA Washington University St Louis Oncology Division St.LouisMO 63100USA meinig School of Biomedical Engineering Cornell UniversityIthacaNY 14853USA The Feil Family Brain and mind Research Institute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic *** advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation *** To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA *** length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational *** Telomere elongation occurred during spaceflight and shortened after return to ***-free DNA analysis revealed increased immune cell signatures *** significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was *** long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months *** Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to *** sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career *** study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.

关键词： genomes clonal hematopoiesis stability immune mitochondria ribosomes spaceflight

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Cell-type resolved transcriptomic approaches for dissecting selective vulnerability in neurodgeneration

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Neural Regeneration Research 2024年第7期19卷 1411-1413页

作者： caleb A.Wood Nicholas m.Tran Department of Neuroscience Baylor College of MedicineHoustonTXUSA Department of molecular and Human Genetics Baylor College of MedicineHoustonTXUSA

A common feature among neurodegenerative conditions is that ce rtain neuronal populations are selectively vulnerable to loss(Fu et al.,2018).By corollary,other neurons are selectively resilient,suggesting they may possess unique features that support their survival.U nderstanding the basis of neuronal resilience or vulnerability would provide a logical strategy to identify factors that could be targeted therapeutically.

关键词： selective targeted

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Integrated Single-cell multiomic Analysis of HIV Latency Reversal Reveals Novel Regulators of Viral Reactivation

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Genomics, Proteomics & Bioinformatics 2024年第1期22卷 67-88页

作者： manickam Ashokkumar Wenwen mei Jackson J.Peterson Yuriko Harigaya David m.murdoch David m.margolis caleb Kornfein Alex Oesterling Zhicheng Guo Cynthia D.Rudin Yuchao Jiang Edward P.Browne Department of medicine University of North Carolina at Chapel HillChapel HillNC 27599USA HIV Cure Center University of North Carolina at Chapel HillChapel HillNC 27599USA Department of Biostatistics University of North Carolina at Chapel HillChapel HillNC 27599USA Department of microbiology and Immunology University of North Carolina at Chapel HillChapel HillNC 27599USA Department of Genetics University of North Carolina at Chapel HillChapel HillNC 27599USA Department of medicine Duke UniversityDurhamNC 27708USA Department of Computer Science Duke UniversityDurhamNC 27708USA Department of Statistics Texas A&M UniversityCollege StationTX 77843USA Department of Biology Texas A&M UniversityCollege StationTX 77843USA Department of Biomedical Engineering Texas A&M UniversityCollege StationTX 77843USA

Despite the success of antiretroviral therapy,human immunodeficiency virus(HIV)cannot be cured because of a reservoir of latently infected cells that evades *** understand the mechanisms of HIV latency,we employed an integrated single-cell RNA sequencing(scRNA-seq)and single-cell assay for transposase-accessible chromatin with sequencing(scATAC-seq)approach to simultaneously profile the transcriptomic and epigenomic characteristics of~125,000 latently infected primary CD4^(+)T cells after reactivation using three different latency reversing *** expressed genes and differentially accessible motifs were used to examine transcriptional pathways and transcription factor(TF)activities across the cell *** identified cellular transcripts and TFs whose expression/activity was correlated with viral reactivation and demonstrated that a machine learning model trained on these data was 75%-79%accurate at predicting viral ***,we validated the role of two candidate HIV-regulating factors,FOXP1 and GATA3,in viral *** data demonstrate the power of integrated multimodal single-cell analysis to uncover novel relationships between host cell factors and HIV latency.

关键词： HIV latency reversal Primary CD4þT cell Single-cell multiomics HIV-regulating factor machine learning

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同轴静电喷涂法制备核壳靶向示踪重组人白细胞介素Ⅱ微球

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Journal of Chinese Pharmaceutical Sciences 2024年第6期33卷 495-510页

作者：朱源许佳琦陈小艳冯颖淑 caleb Kesse Firempong 何海冰刘宏飞江苏大学药学院江苏镇江212013 江苏苏南药业工业有限公司江苏镇江212400 镇江医学院医学化学研究所镇江市功能化学重点实验室江苏镇江212028 江苏海之宏生物医药有限公司江苏南通226001 沈阳药科大学药学院辽宁沈阳110016

重组人白细胞介素-2(rh IL-2)具有促进免疫细胞增殖和分化的潜能,可用于治疗肺癌。然而,rh IL-2半衰期短,生物活性不稳定,需要将其载入微球中进行缓释给药。本研究采用同轴静电喷涂技术制备了载rh IL-2的核壳微球。以量子点为示踪材料,... 详细信息

重组人白细胞介素-2(rh IL-2)具有促进免疫细胞增殖和分化的潜能,可用于治疗肺癌。然而,rh IL-2半衰期短,生物活性不稳定,需要将其载入微球中进行缓释给药。本研究采用同轴静电喷涂技术制备了载rh IL-2的核壳微球。以量子点为示踪材料,核层用壳聚糖做载体包裹rh IL-2和量子点偶联物,壳层采用透明质酸做载体制备核壳复合微球。采用单因素法对载体浓度、电压、针孔内径、喷雾流量等因素进行了研究。优化了同轴静电喷雾法制备核壳微球的工艺参数。结果表明,制备的核壳微球粒径在1.2–2.0μm,包封率和载药量分别为78.39%±1.96%和19.58±2.76μg/mg。体外释放实验显示微球释放效果较好,无突释现象。该制剂的生物学活性实验表明,核壳微球中的rh IL-2与游离蛋白药物具有相同的作用。体内成像分析也显示微球具有主动靶向性。本研究为rh IL-2靶向缓释微球的研制提供了理论依据。

关键词：同轴静电喷雾量子点透明质酸微球

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Control of Cell Wall Extensibility during Pollen Tube Growth

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molecular Plant 2013年第4期6卷 998-1017页

作者： Peter K. Hepler caleb m. Rounds Lawrence J. Winship Biology Department University of Massachusetts Amherst MA 01003 USA School of Natural Science Hampshire College Amherst MA 01002 USA

In this review, we address the question of how the tip-growing pollen tube achieves its rapid rate of elongation while maintaining an intact cell wall. Although turgor is essential for growth to occur, the local expansion rate is controlled by local changes in the viscosity of the apical wall. We focus on several different structures and underly- ing processes that are thought to be major participants including exocytosis, the organization and activity of the actin cytoskeleton, calcium and proton physiology, and cellular energetics. We think that the actin cytoskeleton, in particular the apical cortical actin fringe, directs the flow of vesicles to the apical domain, where they fuse with the plasma mem- brane and contribute their contents to the expanding cell wall. While pH gradients, as generated by a proton-ATPase located on the plasma membrane along the side of the clear zone, may regulate rapid actin turnover and new polymeri- zation in the fringe, the tip-focused calcium gradient biases secretion towards the polar axis. The recent data showing that exocytosis of new wall material precedes and predicts the process of cell elongation provide support for the idea that the intussusception of newly secreted pectin contributes to decreases in apical wall viscosity and to cell expansion. Other prime factors will be the localization and activity of the enzyme pectin methyl-esterase, and the chelation of calcium by pectic acids. Finally, we acknowledge a role for reactive oxygen species in the control of wall viscosity.

关键词： cell expansion cell walls cytoskeleton dynamics polarity pollen development.

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LEAD POISONING IN ANCIENT ROmE: THE STATE OF THE QUESTION

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Journal of Ancient Civilizations 2022年第2期37卷 225-246,276页

作者： Stanley m.Burstein caleb E.Finch California State University Los Angeles The University of Southern California

Introduction Lead pollution as a significant health hazard appears frequently in the news,sometimes spectacularly so as in the case of the recent contamination of the watersupplyof the cityof Flint,michiganbecause of itsuse inlead pipes in the system.'As a result,it is easy to assume that environmental lead pollution is a recent problem,but that is not the *** exposure is,in fact.

关键词： pollution Flint pipes

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Probing Electrocatalytic CO_(2) Reduction at Individual Cu Nanostructures via Optically Targeted Electrochemical Cell microscopy

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Journal of Analysis and Testing 2019年第2期3卷 140-149页

作者： Joshua D.Walmsley Joshua W.Hill Partha Saha caleb m.Hill Department of Chemistry University of WyomingLaramieWY 82071USA

Optically targeted electrochemical cell microscopy(OTECCm)was applied to measure electrocatalytic rates at individual Cu nanoparticles(NPs)under electrolyte conditions relevant to CO_(2) *** electrocatalytic responses from individual NPs were found to exhibit a wide variation in behavior,with significant NP-to-NP variations in the magnitude of electrocata-lytic currents and necessary overpotentials being *** of these quantities with metrics of NP size suggest no significant variations in the inherent electrocatalytic activity of the NPs with *** element simulations of diffusion in this system demonstrate the observed diffusion-limited currents are significantly smaller than expected,attributable to the presence of a significant amount of residual ligand on the surface of the Cu NPs,which were prepared via an organic phase *** results presented here further demonstrate the promise of techniques which employ correlated optical and electrochemical measurements,such as OTECCm,for studying electrocatalysis at individual NPs.

关键词： Electrochemistry Electrochemical microscopy Nanoparticles CO_(2)reduction

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Efficient VLSI Implementation of the C-mANTEC Conn Algorithm by Using PID Controllers

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Circuits and Systems 2017年第11期8卷 253-260页

作者： J. Jeya caleb m. Kannan Department of ECE Saveetha Engineering College Chennai India Department of ECE MIT Campus Anna University Chennai India

Through the research on the existing C-mANTEC neural network and PID control technology, this paper presents an improved C-mANTEC algorithm based on PID control system. The combining of the artificial neural networks with conventional PID control helps in exploring their respective advantages to forming the intelligent PID control. From UCI Repository cancer dataset, the developed system is tested. The results show that the scheme can not only improve the speed of the algorithm in the training process but also improve the generalization capability of the network, which further enhances the performance of PID controllers. The overall power consumed is also reduced to a greater extent.

关键词： C-mANTEC PID Generalization Capability Cancer Intelligent Control

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Artemisinin Biosynthesis in Non-glandular Trichome Cells of Artemisia annua

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molecular Plant 2019年第5期12卷 704-714页

作者： Rika Judd m.caleb Bagley mingzhuo Li Yue Zhu Caiyan Lei Seyit Yuzuak mans Ekelof Gaobin Pu Xiting Zhao David C.muddiman De-Yu Xie Department of Plant and microbial Biology North Carolina State UniversityRaleighNCUSA Department of Chemistry North Carolina State UniversityRaleighNCUSA

Artemisinin-based combination therapy(ACT)forms the first line of malaria ***,the yield fluctuation of artemisinin has remained an unsolved problem in meeting the global demand for *** problem is mainly caused by the glandular trichome(GT)-specific biosynthesis of artemisinin in all currently used Artemisia annua ***,we report that non-GT cells of self-pollinated inbred *** plants can express the artemisinin biosynthetic *** expression analysis demonstrated the transcription of six known pathway genes in GT-free leaves and calli of inbred *** ***-qTOF-mS/mS analysis showed that these two types of GT-free materials produce artemisinin,artemisinic acid,and arteannuin *** IR-mALDESI image profiling revealed that these three metabolites and dihydroartemisinin are localized in non-GT cells of leaves of inbred *** ***,we employed all the above approaches to examine artemisinin biosynthesis in the reported XL annua glandless(gl)*** resulting data demonstrated that leaves of regenerated gl plantlets biosynthesize ***,these findings not only add new knowledge leading to a revision of the current dogma of artemisinin biosynthesis inannua but also may expedite innovation of novel metabolic engineering approaches for high and stable production of artemisinin in the future.

关键词： Artemisia annua artemisinin glandular trichome norvglandular trichome cell

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Intraoperative endoscopic retrograde cholangiopancreatography for traumatic pancreatic ductal injuries:Two case reports

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World Journal of Gastrointestinal Endoscopy 2022年第5期14卷 342-350页

作者： Andrew Canakis Varun Kesar caleb Hudspath Raymond E Kim Thomas m Scalea Peter Darwin Division of Gastroenterology and Hepatology University of Maryland School of MedicineBaltimoreMD 21201United States Department of Surgery R.Adams Cowley Shock Trauma CenterUniversity of Maryland School of MedicineBaltimoreMD 21201United States

BACKGROUND In order to successfully manage traumatic pancreatic duct(PD)leaks,early diagnosis and operative management is paramount in reducing morbidity and *** the acute setting,endoscopic retrograde cholangiopancreatography(ERCP)can be a useful,adjunctive modality during exploratory *** with sphincterotomy and stent placement improves preferential drainage in the setting of injury,allowing the pancreatic leak to properly ***,data in this acute setting is *** SUmmARY In this case series,a 27-year-old male and 16-year-old female presented with PD leaks secondary to a gunshot wound and blunt abdominal trauma,*** underwent intraoperative ERCP within an average of 5.9 h from time of presentation.A sphincterotomy and plastic pancreatic stent placement was performed with a 100%technical and clinical *** were no associated immediate or long-term *** discharge,both patients underwent repeat ERCP for stent removal with resolution of ductal *** These experiences further demonstrated that widespread adaption and optimal timing of ERCP may improve outcomes in trauma centers.

关键词： Pancreatic ductal injury Pancreatic leaks Endoscopic retrograde cholangiopancreatography Trauma Endoscopic stenting Case report

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