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Contribution Of Advanced Fluorescence Nano Microscopy Towards Revealing Mitotic Chromosome Structure, S W. Botchway, Safana Farooq, A Sajid, I K. Robinson, Mohammed Yousuf 2021 Rutherford Appleton Laboratory, Research Complex at Harwell, Oxford, UK.

Contribution Of Advanced Fluorescence Nano Microscopy Towards Revealing Mitotic Chromosome Structure, S W. Botchway, Safana Farooq, A Sajid, I K. Robinson, Mohammed Yousuf

Centre for Regenerative Medicine & Stem Cell Research

The organization of chromatin into higher-order structures and its condensation process represent one of the key challenges in structural biology. This is important for elucidating several disease states. To address this long-standing problem, development of advanced imaging methods has played an essential role in providing understanding into mitotic chromosome structure and compaction. Amongst these are two fast evolving fluorescence imaging technologies, specifically fluorescence lifetime imaging (FLIM) and super-resolution microscopy (SRM). FLIM in particular has been lacking in the application of chromosome research while SRM has been successfully applied although not widely. Both these techniques are capable of providing fluorescence imaging ...


Systemic Tissue And Cellular Disruption From Sars-Cov-2 Infection Revealed In Covid- 19 Autopsies And Spatial Omics Tissue Maps, Jiwoon Park, Jonathan Foox, Tyler Hether, Afshin Beheshti, Amanda Saravia-Butler, Urminder Singh, Eve Syrkin Wurtele, et al. 2021 Weill Cornell Medicine

Systemic Tissue And Cellular Disruption From Sars-Cov-2 Infection Revealed In Covid- 19 Autopsies And Spatial Omics Tissue Maps, Jiwoon Park, Jonathan Foox, Tyler Hether, Afshin Beheshti, Amanda Saravia-Butler, Urminder Singh, Eve Syrkin Wurtele, Et Al.

Genetics, Development and Cell Biology Publications

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus has infected over 115 million people and caused over 2.5 million deaths worldwide. Yet, the molecular mechanisms underlying the clinical manifestations of COVID-19, as well as what distinguishes them from common seasonal influenza virus and other lung injury states such as Acute Respiratory Distress Syndrome (ARDS), remains poorly understood. To address these challenges, we combined transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues, matched with spatial protein and expression profiling (GeoMx) across 357 tissue sections. These results define both body-wide and tissue-specific (heart, liver, lung, kidney ...


Somatic Pirnas And Transposons Are Differentially Regulated During Skeletal Muscle Atrophy And Programmed Cell Death [Preprint], Junko Tsuji, Travis Thomson, Christine Brown, Subhanita Ghosh, William E. Theurkauf, Zhiping Weng, Lawrence M. Schwartz 2021 University of Massachusetts Medical School

Somatic Pirnas And Transposons Are Differentially Regulated During Skeletal Muscle Atrophy And Programmed Cell Death [Preprint], Junko Tsuji, Travis Thomson, Christine Brown, Subhanita Ghosh, William E. Theurkauf, Zhiping Weng, Lawrence M. Schwartz

University of Massachusetts Medical School Faculty Publications

PiWi-interacting RNAs (piRNAs) are small single-stranded RNAs that can repress transposon expression via epigenetic silencing and transcript degradation. They have been identified predominantly in the ovary and testis, where they serve essential roles in transposon silencing in order to protect the integrity of the genome in the germline. The potential expression of piRNAs in somatic cells has been controversial. In the present study we demonstrate the expression of piRNAs derived from both genic and transposon RNAs in the intersegmental muscles (ISMs) from the tobacco hawkmoth Manduca sexta. These piRNAs are abundantly expressed, are ~27 nt long, map antisense to transposons ...


College Of Natural Sciences Newsletter, March 2021, College Of Natural Sciences 2021 South Dakota State University

College Of Natural Sciences Newsletter, March 2021, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Volume 2. Issue 3

Contents:

Page 1 Dean's Message
Page 2-3 Awards and Recognition
Page 4 Student Club Spotlight: MICROBIOLOGY CLUB
Page 5 Research Spotlight: Dr. Chakravarty
Page 6 Open PRAIRIE Data; Grants Awarded in CNS; Research Collquia
Page 7 A Busy Month in Review; Media Coverage of the College


Inhibition Of Zika Virus Replication By G-Quadruplex-Binding Ligands, Indian Institute of Technology Indore, Aryamav Pattnaik, Bikash R. Sahoo, Uma Shankar, Asit K. Pattnaik, Amit Kumar, Debasis Nayak 2021 Indian Institute of Technology Indore

Inhibition Of Zika Virus Replication By G-Quadruplex-Binding Ligands, Indian Institute Of Technology Indore, Aryamav Pattnaik, Bikash R. Sahoo, Uma Shankar, Asit K. Pattnaik, Amit Kumar, Debasis Nayak

Virology Papers

Zika virus (ZIKV), a mosquito-transmitted Flavivirus, emerged in the last decade causing serious diseases and affecting human health globally. Currently, no licensed vaccines or antivirals are available to combat ZIKV, although several vaccine candidates are in the pipeline. In recent years, the presence of non-canonical G-quadruplex (GQ) secondary structures in viral genomes has ignited significant attention as potential targets for antiviral strategy. In this study, we identified several novel conserved potential GQ structures by analyzing published ZIKV genome sequences using an in-house algorithm. Biophysical and biochemical analysis of the RNA sequences containing these potential GQ sequences suggested the existence of ...


Relaxed Tarantula Skeletal Muscle Has Two Atp Energy-Saving Mechanisms, Weikang Ma, Sebastian Duno-Miranda, Thomas Irving, Roger W. Craig, Raul A. Padron 2021 Illinois Institute of Technology

Relaxed Tarantula Skeletal Muscle Has Two Atp Energy-Saving Mechanisms, Weikang Ma, Sebastian Duno-Miranda, Thomas Irving, Roger W. Craig, Raul A. Padron

Radiology Publications

Myosin molecules in the relaxed thick filaments of striated muscle have a helical arrangement in which the heads of each molecule interact with each other, forming the interacting-heads motif (IHM). In relaxed mammalian skeletal muscle, this helical ordering occurs only at temperatures > 20 degrees C and is disrupted when temperature is decreased. Recent x-ray diffraction studies of live tarantula skeletal muscle have suggested that the two myosin heads of the IHM (blocked heads [BHs] and free heads [FHs]) have very different roles and dynamics during contraction. Here, we explore temperature-induced changes in the BHs and FHs in relaxed tarantula skeletal ...


Deficient Spermiogenesis In Mice Lacking Rlim, Feng Wang, Maria Gracia Gervasi, Ana Boskovic, Fengyun Sun, Vera D. Rinaldi, Jun Yu, Mary C. Wallingford, Darya A. Tourzani, Jesse Mager, Lihua Julie Zhu, Oliver J. Rando, Pablo E. Visconti, Lara Strittmatter, Ingolf Bach 2021 University of Massachusetts Medical School

Deficient Spermiogenesis In Mice Lacking Rlim, Feng Wang, Maria Gracia Gervasi, Ana Boskovic, Fengyun Sun, Vera D. Rinaldi, Jun Yu, Mary C. Wallingford, Darya A. Tourzani, Jesse Mager, Lihua Julie Zhu, Oliver J. Rando, Pablo E. Visconti, Lara Strittmatter, Ingolf Bach

Radiology Publications

The X-linked gene Rlim plays major roles in female mouse development and reproduction, where it is crucial for the maintenance of imprinted X chromosome inactivation in extraembryonic tissues of embryos. However, while females carrying a systemic Rlim knockout (KO) die around implantation, male Rlim KO mice appear healthy and are fertile. Here, we report an important role for Rlim in testis where it is highly expressed in post-meiotic round spermatids as well as in Sertoli cells. Systemic deletion of the Rlim gene results in lower numbers of mature sperm that contains excess cytoplasm, leading to decreased sperm motility and in ...


Collagen Has A Unique Sec24 Preference For Efficient Export From The Endoplasmic Reticulum, Chung-Ling Lu, Jacob Cain, Jon Brudvig, Steven Ortmeier, Simeon A. Boyadjiev, Jill M. Weimer, Jinoh Kim 2021 Iowa State University

Collagen Has A Unique Sec24 Preference For Efficient Export From The Endoplasmic Reticulum, Chung-Ling Lu, Jacob Cain, Jon Brudvig, Steven Ortmeier, Simeon A. Boyadjiev, Jill M. Weimer, Jinoh Kim

Biomedical Sciences Publications

Procollagen requires COPII coat proteins for export from the endoplasmic reticulum (ER). SEC24 is the major component of the COPII proteins that selects cargo during COPII vesicle assembly. There are four paralogs (A to D) of SEC24 in mammals, which are classified into two subgroups. Pathological mutations in SEC24D cause osteogenesis imperfecta with craniofacial dysplasia in humans and sec24d mutant fish also recapitulate this phenotypes. Consistent with the skeletal phenotypes, the secretion of collagen was severely defective in mutant fish, emphasizing the importance of SEC24D in collagen secretion. However, SEC24D patient derived fibroblasts show only a mild secretion phenotype, suggesting ...


Differential Role Of Mlkl In Alcohol-Associated And Non-Alcohol-Associated Fatty Liver Diseases In Mice And Humans, Tatsunori Miyata, Bruce A. Barton, Laura E. Nagy 2021 Kumamoto University Hospital

Differential Role Of Mlkl In Alcohol-Associated And Non-Alcohol-Associated Fatty Liver Diseases In Mice And Humans, Tatsunori Miyata, Bruce A. Barton, Laura E. Nagy

University of Massachusetts Medical School Faculty Publications

Hepatocellular death contributes to progression of alcohol-associated (ALD-associated) and non-alcohol-associated (NAFL/NASH) liver diseases. However, receptor-interaction protein kinase 3 (RIP3), an intermediate in necroptotic cell death, contributes to injury in murine models of ALD but not NAFL/NASH. We show here that a differential role for mixed-lineage kinase domain-like protein (MLKL), the downstream effector of RIP3, in murine models of ALD versus NAFL/NASH and that RIP1-RIP3-MLKL can be used as biomarkers to distinguish alcohol-associated hepatitis (AH) from NASH. Phospho-MLKL was higher in livers of patients with NASH compared with AH or healthy controls (HCs). MLKL expression, phosphorylation, oligomerization, and ...


Annotation Of Chromatin States In 66 Complete Mouse Epigenomes During Development, Arjan van der Velde, Kaili Fan, Junko Tsuji, Jill E. Moore, Michael J. Purcaro, Henry E. Pratt, Zhiping Weng 2021 University of Massachusetts Medical School

Annotation Of Chromatin States In 66 Complete Mouse Epigenomes During Development, Arjan Van Der Velde, Kaili Fan, Junko Tsuji, Jill E. Moore, Michael J. Purcaro, Henry E. Pratt, Zhiping Weng

Open Access Publications by UMMS Authors

The morphologically and functionally distinct cell types of a multicellular organism are maintained by their unique epigenomes and gene expression programs. Phase III of the ENCODE Project profiled 66 mouse epigenomes across twelve tissues at daily intervals from embryonic day 11.5 to birth. Applying the ChromHMM algorithm to these epigenomes, we annotated eighteen chromatin states with characteristics of promoters, enhancers, transcribed regions, repressed regions, and quiescent regions. Our integrative analyses delineate the tissue specificity and developmental trajectory of the loci in these chromatin states. Approximately 0.3% of each epigenome is assigned to a bivalent chromatin state, which harbors ...


Xct-Driven Expression Of Gpx4 Determines Sensitivity Of Breast Cancer Cells To Ferroptosis Inducers, Namgyu Lee, Anne E. Carlisle, Austin Peppers, Sung Jin Park, Mihir B. Doshi, Meghan E. Spears, Dohoon Kim 2021 University of Massachusetts Medical School

Xct-Driven Expression Of Gpx4 Determines Sensitivity Of Breast Cancer Cells To Ferroptosis Inducers, Namgyu Lee, Anne E. Carlisle, Austin Peppers, Sung Jin Park, Mihir B. Doshi, Meghan E. Spears, Dohoon Kim

Open Access Publications by UMMS Authors

Inducers of ferroptosis such as the glutathione depleting agent Erastin and the GPX4 inhibitor Rsl-3 are being actively explored as potential therapeutics in various cancers, but the factors that determine their sensitivity are poorly understood. Here, we show that expression levels of both subunits of the cystine/glutamate antiporter xCT determine the expression of GPX4 in breast cancer, and that upregulation of the xCT/selenocysteine biosynthesis/GPX4 production axis paradoxically renders the cancer cells more sensitive to certain types of ferroptotic stimuli. We find that GPX4 is strongly upregulated in a subset of breast cancer tissues compared to matched normal ...


Yap And Taz Are Transcriptional Co-Activators Of Ap-1 Proteins And Stat3 During Breast Cellular Transformation [Preprint], Lizhi He, Henry E. Pratt, Fengxiang Wei, Mingshi Gao, Zhiping Weng, Kevin Struhl 2021 Harvard Medical School

Yap And Taz Are Transcriptional Co-Activators Of Ap-1 Proteins And Stat3 During Breast Cellular Transformation [Preprint], Lizhi He, Henry E. Pratt, Fengxiang Wei, Mingshi Gao, Zhiping Weng, Kevin Struhl

University of Massachusetts Medical School Faculty Publications

The YAP and TAZ paralogues are transcriptional co-activators recruited to target sites, primarily by TEAD proteins. Here, we show that YAP and TAZ are also recruited by JUNB and STAT3, key factors that mediate an epigenetic switch linking inflammation to cellular transformation. YAP and TAZ directly interact with JUNB and STAT3 via a WW domain important for transformation, co-occupy many target sites in vivo via AP-1 and (to a lesser extent) STAT3 sequence motifs, and stimulate transcriptional activation by AP-1 proteins. A few target sites are YAP- or TAZ-specific, and they are associated with different sequence motifs and gene classes ...


Slim Shady Is A Novel Allele Of Phytochrome B Present In The T-Dna Line Salk_015201, Linkan Dash, Robert E. McEwan, Christian Montes, Ludvin Mejia, Justin W. Walley, Brian P. Dilkes, Dior R. Kelley 2021 Iowa State University

Slim Shady Is A Novel Allele Of Phytochrome B Present In The T-Dna Line Salk_015201, Linkan Dash, Robert E. Mcewan, Christian Montes, Ludvin Mejia, Justin W. Walley, Brian P. Dilkes, Dior R. Kelley

Genetics, Development and Cell Biology Publications

Auxin is a hormone that is required for hypocotyl elongation during seedling development. In response to auxin rapid changes in transcript and protein abundance occur in hypocotyls and some auxin responsive gene expression is linked to hypocotyl growth. To functionally validate proteomic studies, a reverse genetics screen was performed on mutants in auxin-regulated proteins to identify novel regulators of plant growth. This uncovered a long hypocotyl mutant, which we called slim shady, in an annotated insertion line in IMMUNOREGULATORY RNA-BINDING PROTEIN (IRR). Overexpression of the IRR gene failed to rescue the slim shady phenotype and characterization of a second T-DNA ...


Cohesin Mutations Alter Dna Damage Repair And Chromatin Structure And Create Therapeutic Vulnerabilities In Mds/Aml, Zuzana Tothova, Anne-Laure Valton, Sergey V. Venev, Job Dekker, Benjamin L. Ebert 2021 Dana-Farber Cancer Institute

Cohesin Mutations Alter Dna Damage Repair And Chromatin Structure And Create Therapeutic Vulnerabilities In Mds/Aml, Zuzana Tothova, Anne-Laure Valton, Sergey V. Venev, Job Dekker, Benjamin L. Ebert

Open Access Publications by UMMS Authors

The cohesin complex plays an essential role in chromosome maintenance and transcriptional regulation. Recurrent somatic mutations in the cohesin complex are frequent genetic drivers in cancer, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Here, using genetic dependency screens of stromal antigen 2-mutant (STAG2-mutant) AML, we identified DNA damage repair and replication as genetic dependencies in cohesin-mutant cells. We demonstrated increased levels of DNA damage and sensitivity of cohesin-mutant cells to poly(ADP-ribose) polymerase (PARP) inhibition. We developed a mouse model of MDS in which Stag2 mutations arose as clonal secondary lesions in the background of clonal hematopoiesis driven ...


Dna Repair Pathways In Cancer Therapy And Resistance, Lan-ya Li, Yi-di Guan, Xi-sha Chen, Jin-ming Yang, Yan Cheng 2021 Central South University, China

Dna Repair Pathways In Cancer Therapy And Resistance, Lan-Ya Li, Yi-Di Guan, Xi-Sha Chen, Jin-Ming Yang, Yan Cheng

Toxicology and Cancer Biology Faculty Publications

DNA repair pathways are triggered to maintain genetic stability and integrity when mammalian cells are exposed to endogenous or exogenous DNA-damaging agents. The deregulation of DNA repair pathways is associated with the initiation and progression of cancer. As the primary anti-cancer therapies, ionizing radiation and chemotherapeutic agents induce cell death by directly or indirectly causing DNA damage, dysregulation of the DNA damage response may contribute to hypersensitivity or resistance of cancer cells to genotoxic agents and targeting DNA repair pathway can increase the tumor sensitivity to cancer therapies. Therefore, targeting DNA repair pathways may be a potential therapeutic approach for ...


Macrophage And Adipocyte Interaction As A Source Of Inflammation In Kidney Disease, Cristina Martos-Rus, Goni Katz-Greenberg, Zhao Lin, Eurico Serrano, Diana Whitaker Menezes, Marina Domingo-Vidal, Megan Roche, Kavitha Ramaswamy, D. Craig Hooper, Bonita Falkner, Maria P Martinez Cantarin 2021 Thomas Jefferson University

Macrophage And Adipocyte Interaction As A Source Of Inflammation In Kidney Disease, Cristina Martos-Rus, Goni Katz-Greenberg, Zhao Lin, Eurico Serrano, Diana Whitaker Menezes, Marina Domingo-Vidal, Megan Roche, Kavitha Ramaswamy, D. Craig Hooper, Bonita Falkner, Maria P Martinez Cantarin

Kimmel Cancer Center Faculty Papers

In obesity, adipose tissue derived inflammation is associated with unfavorable metabolic consequences. Uremic inflammation is prevalent and contributes to detrimental outcomes. However, the contribution of adipose tissue inflammation in uremia has not been characterized. We studied the contribution of adipose tissue to uremic inflammation in-vitro, in-vivo and in human samples. Exposure to uremic serum resulted in activation of inflammatory pathways including NFκB and HIF1, upregulation of inflammatory cytokines/chemokines and catabolism with lipolysis, and lactate production. Also, co-culture of adipocytes with macrophages primed by uremic serum resulted in higher inflammatory cytokine expression than adipocytes exposed only to uremic serum. Adipose ...


Cell Cycle Progression Effects Of Albumin, Sharmeen Uddin 2021 The Graduate Center, City University of New York

Cell Cycle Progression Effects Of Albumin, Sharmeen Uddin

Dissertations, Theses, and Capstone Projects

Progression through G1 phase of the cell cycle is controlled largely by growth factors in early G1 and by nutrients in late G1 indicating sufficient raw material for cell division. We previously mapped a late G1 cell cycle checkpoint for lipids upstream from a mammalian target of rapamycin complex 1 (mTORC1)-mediated checkpoint and downstream from a mid-G1 checkpoint known as the Restriction point. We therefore investigated a role for lipids in progression through late G1 into S-phase. Quiescent BJ-hTERT human fibroblasts primed back into G1 with FBS treatment, were treated with a mixture ...


The N Terminus Of Myosin-Binding Protein C Extends Toward Actin Filaments In Intact Cardiac Muscle, Sheema Rahmanseresht, Kyoung H. Lee, Thomas S. O'Leary, James W. McNamara, Sakthivel Sadayappan, Jeffrey Robbins, David M. Warshaw, Roger W. Craig, Michael J. Previs 2021 University of Vermont

The N Terminus Of Myosin-Binding Protein C Extends Toward Actin Filaments In Intact Cardiac Muscle, Sheema Rahmanseresht, Kyoung H. Lee, Thomas S. O'Leary, James W. Mcnamara, Sakthivel Sadayappan, Jeffrey Robbins, David M. Warshaw, Roger W. Craig, Michael J. Previs

Radiology Publications

Myosin and actin filaments are highly organized within muscle sarcomeres. Myosin-binding protein C (MyBP-C) is a flexible, rod-like protein located within the C-zone of the sarcomere. The C-terminal domain of MyBP-C is tethered to the myosin filament backbone, and the N-terminal domains are postulated to interact with actin and/or the myosin head to modulate filament sliding. To define where the N-terminal domains of MyBP-C are localized in the sarcomere of active and relaxed mouse myocardium, the relative positions of the N terminus of MyBP-C and actin were imaged in fixed muscle samples using super-resolution fluorescence microscopy. The resolution of ...


Anti-Cancer Effects By Interleukin 24, Xuelin Zhong 2021 The Graduate Center, City University of New York

Anti-Cancer Effects By Interleukin 24, Xuelin Zhong

Dissertations, Theses, and Capstone Projects

Cancers develop as some cells acquire the ability, either by exogenous stimulation or by spontaneous mutation, to keep growing despite normal restraints. Up-regulating translation of oncogenes involved in cell proliferation and tumor development and down-regulating translation of tumor-suppressors that normally suppress tumor development are two most common mechanisms by which cancers develop. Therefore, it is crucial to study how these proteins get either up-regulated or down-regulated at translational level.

The eukaryotic translation initiation factor, which is composed of subunits such as eIF4A, eIF4G and eIF4E, is one of the key factors that contribute to efficient translation initiation. Interleukin 24 (IL-24 ...


Modulation Of Bacterial Fitness And Virulence Through Antisense Rnas, Jess A. Millar, Rahul Raghavan 2021 University of Michigan

Modulation Of Bacterial Fitness And Virulence Through Antisense Rnas, Jess A. Millar, Rahul Raghavan

Biology Faculty Publications and Presentations

Regulatory RNAs contribute to gene expression control in bacteria. Antisense RNAs (asRNA) are a class of regulatory RNAs that are transcribed from opposite strands of their target genes. Typically, these untranslated transcripts bind to cognate mRNAs and rapidly regulate gene expression at the post-transcriptional level. In this article, we review asRNAs that modulate bacterial fitness and increase virulence. We chose examples that underscore the variety observed in nature including, plasmid- and chromosome-encoded asRNAs, a riboswitch-regulated as RNA, and as RNAs that require other RNAs or RNA binding proteins for stability and activity. We explore how as RNAs improve bacterial fitness ...


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