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TCF1 in T cell immunity: a broadened frontier.

Nat Rev Immunol 2021 Jun 14. Epub 2021 Jun 14.

Center for Discovery and Innovation, Hackensack University Medical Center, Nutley, NJ, USA.

TCF1 and its homologue LEF1 are historically known as effector transcription factors downstream of the WNT signalling pathway and are essential for early T cell development. Recent advances bring TCF1 into the spotlight for its versatile, context-dependent functions in regulating mature T cell responses. In the cytotoxic T cell lineages, TCF1 is required for the self-renewal of stem-like CD8 T cells generated in response to viral or tumour antigens, and for preserving heightened responses to checkpoint blockade immunotherapy. Read More

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Automated generation of context-specific gene regulatory networks with a weighted approach in .

Interface Focus 2021 Jun 11;11(4):20200076. Epub 2021 Jun 11.

Laboratorio de Biología de Redes, Centro de Genónica y Bioinformática, Facultad de Ciencias, Universidad Mayor, Santiago 8580745, Chile.

The regulation of gene expression is a key factor in the development and maintenance of life in all organisms. Even so, little is known at whole genome scale for most genes and contexts. We propose a method, Tool for Weighted Epigenomic Networks in (Fly T-WEoN), to generate context-specific gene regulatory networks starting from a reference network that contains all known gene regulations in the fly. Read More

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Effects of miR‑210‑3p on the erythroid differentiation of K562 cells under hypoxia.

Mol Med Rep 2021 Aug 10;24(2). Epub 2021 Jun 10.

Department of Biochemistry, Qing Hai University Medical College, Xining, Qinghai 810000, P.R. China.

GATA binding protein 1 (GATA‑1) is one of the most important hematopoietic transcription factors in the production of blood cells, such as platelets, eosinophils, mast cells and erythrocytes. GATA‑1 regulates the participation of microRNA (miRNAs/miRs) in erythroid differentiation under normoxia. However, GATA‑1 expression and the regulation of miR‑210‑3p in the context of erythroid differentiation under hypoxia remain unknown. Read More

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Mechanoregulation of YAP and TAZ in Cellular Homeostasis and Disease Progression.

Front Cell Dev Biol 2021 24;9:673599. Epub 2021 May 24.

Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, United States.

Biophysical cues, such as mechanical properties, play a critical role in tissue growth and homeostasis. During organ development and tissue injury repair, compressive and tensional forces generated by cell-extracellular matrix or cell-cell interaction are key factors for cell fate determination. In the vascular system, hemodynamic forces, shear stress, and cyclic stretch modulate vascular cell phenotypes and susceptibility to atherosclerosis. Read More

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Biomarkers for Deep Brain Stimulation in Animal Models of Depression.

Neuromodulation 2021 Jun 9. Epub 2021 Jun 9.

Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA.

Objectives: Despite recent advances in depression treatment, many patients still do not respond to serial conventional therapies and are considered "treatment resistant." Deep brain stimulation (DBS) has therapeutic potential in this context. This comprehensive review of recent studies of DBS for depression in animal models identifies potential biomarkers for improving therapeutic efficacy and predictability of conventional DBS to aid future development of closed-loop control of DBS system. Read More

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Water quality assessment of the Demetrio stream: an affluent of the Gravataí River in the South of Brazil.

Braz J Biol 2021 4;82:e234692. Epub 2021 Jun 4.

Universidade La Salle - Unilasalle, Canoas, RS, Brasil.

The Gravataí River basin, one of the main water sources of the metropolitan region of Porto Alegre, is among the ten most polluted rivers in Brazil. Water quality is monitored only through physico-chemical and microbiological parameters in Brazil, and in this context, considering the importance of the use of biomarkers in complementing the analysis of water, the present study aimed to evaluate the environmental quality of the main affluent of the Gravataí River, Demetrio stream, through physico-chemical, microbiological, and cytogenotoxic criteria, at the stream source (P1), whereas samples P2 and P3 were obtained from the upstream near the area with the highest urban density and the downstream near the meeting point with the Gravataí River, respectively. The results for copper concentration and color classified the Demetrio stream as Class 4 in general, that is, the water is suitable only for navigation and to landscape harmony. Read More

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Known sequence features can explain half of all human gene ends.

NAR Genom Bioinform 2021 Jun 4;3(2):lqab042. Epub 2021 Jun 4.

Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.

Cleavage and polyadenylation (CPA) sites define eukaryotic gene ends. CPA sites are associated with five key sequence recognition elements: the upstream UGUA, the polyadenylation signal (PAS), and U-rich sequences; the CA/UA dinucleotide where cleavage occurs; and GU-rich downstream elements (DSEs). Currently, it is not clear whether these sequences are sufficient to delineate CPA sites. Read More

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Analysis of single-cell RNA sequencing data based on autoencoders.

BMC Bioinformatics 2021 Jun 8;22(1):309. Epub 2021 Jun 8.

Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Cambridge, CB2 0AW, UK.

Background: Single-cell RNA sequencing (scRNA-Seq) experiments are gaining ground to study the molecular processes that drive normal development as well as the onset of different pathologies. Finding an effective and efficient low-dimensional representation of the data is one of the most important steps in the downstream analysis of scRNA-Seq data, as it could provide a better identification of known or putatively novel cell-types. Another step that still poses a challenge is the integration of different scRNA-Seq datasets. Read More

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A Comprehensive Departmental Care Review Model: Requirements, Structure, and Flow.

Jt Comm J Qual Patient Saf 2021 May 21. Epub 2021 May 21.

Background: The Institute of Medicine, the National Patient Safety Foundation, and The Joint Commission have advocated for increased systematic care review to inform future quality improvement. Developing a system to efficiently gather meaningful feedback, review care, and identify areas for improvement can take years to construct. Yet, these systems are vital to reducing future medical error. Read More

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Elucidating Human Mitosis Using an Anaphase-Like Cell-Free System.

Methods Mol Biol 2021 ;2329:143-164

Faculty of Life Sciences and Institute of Nanotechnology and Advanced Materials, Bar-llan University, Ramat-Gan, Israel.

A balanced progression through mitosis and cell division is largely dependent on orderly phosphorylation and ubiquitin-mediated proteolysis of regulatory and structural proteins. These series of events ultimately secure genome stability and time-invariant cellular properties during cell proliferation. Two of the core enzymes regulating mitotic milestones in all eukaryotes are cyclin dependent kinase 1 (CDK1) with its coactivator cyclin B, and the E3 ubiquitin ligase anaphase promoting complex/cyclosome (APC/C). Read More

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January 2021

An Assessment of Ambient Water Quality and Challenges with Access to Water and Sanitation Services for Individuals Experiencing Homelessness in Riverine Encampments.

Environ Eng Sci 2021 May 24;38(5):389-401. Epub 2021 May 24.

School of Public Affairs, San Diego State University, San Diego, California, USA.

Individuals experiencing unsheltered homelessness face significant barriers to accessing water, sanitation, and hygiene services, but the risks associated with this lack of access and barriers to service provision have been largely understudied. We analyzed water samples upstream and downstream of three homeless encampments in the San Diego River watershed and interviewed service providers from public and nonprofit sectors to assess local perceptions about challenges and potential solutions for water and sanitation service provision in this context. Water upstream from encampments contained detectable levels of caffeine and sucralose. Read More

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Anti-allergic actions of a Chinese patent medicine, huoxiangzhengqi oral liquid, in RBL-2H3 cells and in mice.

Pharm Biol 2021 Dec;59(1):672-682

Chongqing Academy of Chinese Materia Medica, Chongqing, PR China.

Context: Huoxiangzhengqi oral liquid (HXZQ-OL), a traditional Chinese medicine formula, has antibacterial, anti-inflammation and gastrointestinal motility regulation effects.

Objective: The study investigates the anti-allergic activity and underlying mechanism of HXZQ-OL.

Materials And Methods: IgE/Ag-mediated RBL-2H3 cells were used to evaluate the anti-allergic activity of HXZQ-OL (43. Read More

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December 2021

Neutrophil Elastase Promotes Neointimal Hyperplasia by Targeting TLR4-NFкB Signalling.

Br J Pharmacol 2021 Jun 2. Epub 2021 Jun 2.

Department of Cardiology, and Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China.

Background And Purpose: Neointimal hyperplasia (NIH) is the fundamental cause for vascular diseases, and vascular smooth muscle cell (VSMC) dysregulation has been widely implicated in NIH. Neutrophil elastase (NE) has been suggested as potential therapeutic for multiple diseases. Here we investigated the role of NE in VSMC functions and injury-induced NIH, and further explored the therapeutic potential of targeting NE in NIH. Read More

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Improving Performance of Salt-Grown Crops by Exogenous Application of Plant Growth Regulators.

Biomolecules 2021 May 24;11(6). Epub 2021 May 24.

Tasmanian Institute of Agriculture, University of Tasmania, Prospect 7250, Australia.

Soil salinity is one of the major abiotic stresses restricting plant growth and development. Application of plant growth regulators (PGRs) is a possible practical means for minimizing salinity-induced yield losses, and can be used in addition to or as an alternative to crop breeding for enhancing salinity tolerance. The PGRs auxin, cytokinin, nitric oxide, brassinosteroid, gibberellin, salicylic acid, abscisic acid, jasmonate, and ethylene have been advocated for practical use to improve crop performance and yield under saline conditions. Read More

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Differential Regulation of Cellular FAM111B by Human Adenovirus C Type 5 E1 Oncogenes.

Viruses 2021 May 28;13(6). Epub 2021 May 28.

Department of Viral Transformation, Leibniz Institute for Experimental Virology (HPI), 20251 Hamburg, Germany.

The adenovirus type 5 (HAdV-C5) E1 transcription unit encodes regulatory proteins that are essential for viral replication and transformation. Among these, E1A and E1B-55K act as key multifunctional HAdV-C5 proteins involved in various steps of the viral replication cycle and in virus-induced cell transformation. In this context, HAdV-C5-mediated dysregulations of cellular factors such as the tumor suppressors p53 and pRB have been intensively investigated. Read More

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CUX1 Enhances Pancreatic Cancer Formation by Synergizing with KRAS and Inducing MEK/ERK-Dependent Proliferation.

Cancers (Basel) 2021 May 18;13(10). Epub 2021 May 18.

Department of Internal Medicine I, Martin Luther University Halle-Wittenberg, D06120 Halle/Saale, Germany.

The transcription factor CUX1 has been implicated in either tumor suppression or progression, depending on the cancer entity and the prevalent CUX1 isoform. Previously, we could show that CUX1 acts as an important mediator of tumor cell proliferation and resistance to apoptosis in pancreatic cancer cell lines. However, in vivo evidence for its impact on pancreatic carcinogenesis, isoform-specific effects and downstream signaling cascades are missing. Read More

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Crosstalk between Interleukin-1β and Type I Interferons Signaling in Autoinflammatory Diseases.

Authors:
Philippe Georgel

Cells 2021 May 8;10(5). Epub 2021 May 8.

Laboratoire d'ImmunoRhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S 1109, Institut Thématique Interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Transplantex NG, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, 67085 Strasbourg, France.

Interleukin-1β (IL-1β) and type I interferons (IFNs) are major cytokines involved in autoinflammatory/autoimmune diseases. Separately, the overproduction of each of these cytokines is well described and constitutes the hallmark of inflammasomopathies and interferonopathies, respectively. While their interaction and the crosstalk between their downstream signaling pathways has been mostly investigated in the frame of infectious diseases, little information on their interconnection is still available in the context of autoinflammation promoted by sterile triggers. Read More

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Mitochondrial metabolism: powering new directions in acute myeloid leukemia.

Leuk Lymphoma 2021 Jun 1:1-11. Epub 2021 Jun 1.

Division of Hematology, Department of Medicine, University of British Columbia, Vancouver, Canada.

There has been an explosion of knowledge about the role of metabolism and the mitochondria in acute myeloid leukemia (AML). We have also recently seen several waves of novel therapies change the treatment landscape for AML, such as the selective B-cell lymphoma 2 (BCL-2) inhibitor venetoclax. In this new context, we review the rapidly advancing literature on the role of metabolism and the mitochondria in AML pathogenesis, and how these are interwoven with the mechanisms of action for novel therapeutics in AML. Read More

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Endocannabinoids in immune regulation and immunopathologies.

Immunology 2021 May 30. Epub 2021 May 30.

Dendritic Cell Biology Laboratory, IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata, India.

Endocannabinoids are key bioactive components of the endocannabinoid system and the profound influence of endocannabinoids on the modulation of the immune system is being increasingly appreciated. The knowledge of endocannabinoid-immune cell crosstalk will pave the way to therapeutic implications of modulators of this pathway in autoimmune and chronic inflammatory disorders.Endocannabinoids seem to exert both anti-inflammatory and pro-inflammatory effects in specific contexts, based on specific receptor-engagement and the downstream signaling pathways involved. Read More

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Cellular Signaling Mechanisms of Hypocretin/Orexin.

Front Neurol Neurosci 2021 28;45:91-102. Epub 2021 May 28.

Department of Pharmacology and Department of Physiology, Institute of Biomedicine, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Orexin receptors (OXRs) are promiscuous G-protein-coupled receptors that signal via several G-proteins and, putatively, via other proteins. On which basis the signal pathways are selected and orchestrated is largely unknown. We also have an insufficient understanding of the kind of signaling that is important for specific types of cellular responses. Read More

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Proteoglycan 4 (PRG4) expression and function in dry eye associated inflammation.

Exp Eye Res 2021 Jul 25;208:108628. Epub 2021 May 25.

Biomedical Engineering Department, School of Dental Medicine, UConn Health, Farmington, CT, USA. Electronic address:

Dry eye disease (DED) affects hundreds of millions of people worldwide. It is characterized by the production of inflammatory cytokines and chemokines as well as damaging matrix metalloproteinases (MMPs) at the ocular surface. While proteoglycan 4 (PRG4), a mucin-like glycoprotein present at the ocular surface, is most well known as a boundary lubricant that contributes to ocular surface integrity, it has been shown to blunt inflammation in various cell types, suggesting a dual mechanism of action. Read More

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Effect of Baricitinib on TPA-induced psoriasis like skin inflammation.

Life Sci 2021 May 24;279:119655. Epub 2021 May 24.

Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology, Vellore-632014 India. Electronic address:

Psoriasis is a chronic inflammatory disorder of the skin and is characterized by hyper-dividing keratinocytes. This hyper-proliferation of keratinocytes is due to the high level of inflammatory cytokines. In this study, we evaluated the effect of topically applied Baricitinib, JAK1/2 inhibitor on chronic 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced psoriasis model in mice. Read More

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From the culture broth to the erythritol crystals: an opportunity for circular economy.

Appl Microbiol Biotechnol 2021 Jun 27;105(11):4467-4486. Epub 2021 May 27.

Research Unit of Bioresource and Plant Science, Institute of Chemical, Environmental and Bioscience Engineering, TU Wien, 1060, Vienna, Austria.

The reduction of sugar intake by adults has been stated by the World Health Organization as an important strategy to reduce the risk of non-communicable diseases. Erythritol is a four-carbon sugar alcohol that is considered as a highly suitable substitution for sucrose. This review article covers approaches for the separate stages of the biotechnological production of erythritol from cultivation to the downstream section. Read More

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Loss of a 7q gene, CUX1, disrupts epigenetic-driven DNA repair and drives therapy-related myeloid neoplasms.

Blood 2021 May 26. Epub 2021 May 26.

The University of Chicago, Chicago, Illinois, United States.

Therapy-related myeloid neoplasms (t-MN) are high-risk, late effects in cancer survivors with poorly understood pathogenesis. It has been postulated that, in some cases, hematopoietic stem and progenitor cells (HSPCs) harboring mutations are selected for by cytotoxic exposures and transform. Here, we evaluate this model in the context of deficiency of CUX1, a transcription factor encoded on chromosome 7q and deleted in half of t-MN cases. Read More

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Quercetin Alleviates Neuropathic Pain in the Rat CCI Model by Mediating AMPK/MAPK Pathway.

J Pain Res 2021 19;14:1289-1301. Epub 2021 May 19.

Department of Anesthesiology and Pharmacology, Xuzhou Medical University, Xuzhou, 221000, People's Republic of China.

Context: Quercetin (que) is one abundant flavonol with a variety of biological activities. Previous studies have shown quercetin can reduce neuropathic pain in rats with chronic constriction injury (CCI).

Objective: To evaluate the effects of quercetin on neuropathic pain in CCI model and explore its underlying mechanism in vivo. Read More

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An Unusual Case of Hashimoto's Thyroiditis Presenting as Impending Cardiac Tamponade in a Patient with Acquired Immune Deficiency Syndrome (AIDS).

Am J Case Rep 2021 May 27;22:e929249. Epub 2021 May 27.

Section of Hematology and Oncology, Virginia Mason Medical Center, Seattle, WA, USA.

BACKGROUND Cardiac tamponade is a life-threatening pericardial compressive disorder that is a common downstream manifestation of infections, malignancy, and metabolic disorders. Hypothyroidism is a rare cause of tamponade that is attributed to the slow accumulation of effusive fluid into the intrapericardial space. In individuals living with HIV/AIDS, tamponade is commonly associated with infection or malignancy. Read More

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A systematic analysis of signaling reactivation and drug resistance.

Cell Rep 2021 May;35(8):109157

Systems Biology Ireland, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.

Increasing evidence suggests that the reactivation of initially inhibited signaling pathways causes drug resistance. Here, we analyze how network topologies affect signaling responses to drug treatment. Network-dependent drug resistance is commonly attributed to negative and positive feedback loops. Read More

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DOT1L modulates the senescence-associated secretory phenotype through epigenetic regulation of IL1A.

J Cell Biol 2021 Aug 26;220(8). Epub 2021 May 26.

Department of Pharmacology and Chemical Biology, University of Pittsburgh Medical Center Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Oncogene-induced senescence (OIS) is a stable cell cycle arrest that occurs in normal cells upon oncogene activation. Cells undergoing OIS express a wide variety of secreted factors that affect the senescent microenvironment termed the senescence-associated secretory phenotype (SASP), which is beneficial or detrimental in a context-dependent manner. OIS cells are also characterized by marked epigenetic changes. Read More

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Oligomerization of Lrrk controls actin severing and α-synuclein neurotoxicity in vivo.

Mol Neurodegener 2021 May 24;16(1):33. Epub 2021 May 24.

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Massachusetts, Boston, USA.

Background: Mutations in LRRK2 are the most common cause of familial Parkinson's disease and typically cause disease in the context of abnormal aggregation and deposition of α-synuclein within affected brain tissue.

Methods: We combine genetic analysis of Lrrk-associated toxicity in a penetrant Drosophila model of wild type human α-synuclein neurotoxicity with biochemical analyses and modeling of LRRK2 toxicity in human neurons and transgenic mouse models.

Results: We demonstrate that Lrrk and α-synuclein interact to promote neuronal degeneration through convergent effects on the actin cytoskeleton and downstream dysregulation of mitochondrial dynamics and function. Read More

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Partially hydrolyzed guar gum attenuates non-alcoholic fatty liver disease in mice through the gut-liver axis.

World J Gastroenterol 2021 May;27(18):2160-2176

Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

Background: The gut-liver axis has attracted much interest in the context of chronic liver disease pathogenesis. Prebiotics such as dietary fibers were shown to attenuate non-alcoholic fatty liver disease (NAFLD) by modulating gut microbiota. Partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber, has been reported to alleviate the symptoms of various intestinal diseases and metabolic syndromes. Read More

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