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Impact of chromatin context on Cas9-induced DNA double-strand break repair pathway balance.

Mol Cell 2021 Apr 6. Epub 2021 Apr 6.

Oncode Institute, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands; Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands; Department of Cell Biology, Erasmus University Medical Centre, 3015 CN, Rotterdam, the Netherlands. Electronic address:

DNA double-strand break (DSB) repair is mediated by multiple pathways. It is thought that the local chromatin context affects the pathway choice, but the underlying principles are poorly understood. Using a multiplexed reporter assay in combination with Cas9 cutting, we systematically measure the relative activities of three DSB repair pathways as a function of chromatin context in >1,000 genomic locations. Read More

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Bcl-xL Dynamics under the Lens of Protein Structure Networks.

J Phys Chem B 2021 Apr 13. Epub 2021 Apr 13.

Computational Biology Laboratory, Danish Cancer Society Research Center, 2100 Copenhagen, Denmark.

Understanding the finely orchestrated interactions leading to or preventing programmed cell death (apoptosis) is of utmost importance in cancer research because the failure of these systems could eventually lead to the onset of the disease. In this regard, the maintenance of a delicate balance between the promoters and inhibitors of mitochondrial apoptosis is crucial, as demonstrated by the interplay among the Bcl-2 family members. In particular, B-cell lymphoma extra-large (Bcl-x) is a target of interest due to the forefront role of its dysfunctions in cancer development. Read More

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mTORC1 mediates fiber type-specific regulation of protein synthesis and muscle size during denervation.

Cell Death Discov 2021 Apr 12;7(1):74. Epub 2021 Apr 12.

Department of Comparative Biosciences in the School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.

Skeletal muscle denervation occurs in diverse conditions and causes severe muscle atrophy. Signaling by mammalian target of rapamycin complex 1 (mTORC1) plays a central role in the maintenance of skeletal muscle mass by regulating net protein balance; yet, its role in denervation-induced atrophy is unclear. In this study, by using skeletal muscle-specific and inducible raptor knockout mice, we demonstrate that signaling through mTORC1 is activated during denervation and plays an essential role in mitigating the atrophy of non-type IIB muscle fibers. Read More

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Islet-on-a-chip: Biomimetic micropillar-based microfluidic system for three-dimensional pancreatic islet cell culture.

Biosens Bioelectron 2021 Apr 2;183:113215. Epub 2021 Apr 2.

Medical Biotechnology, Faculty of Chemistry, Warsaw University of Technology, Poland. Electronic address:

Type 2 diabetes is currently one of the most common metabolic diseases, affecting all ages worldwide. As the incidence of type 2 diabetes increases, a growing number of studies focus on islets of Langerhans. A three-dimensional research model that maps islet morphology and maintains hormonal balance in vivo is still needed. Read More

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The microbiota-mediated dietary and nutritional interventions for COVID-19.

Clin Immunol 2021 Apr 9:108725. Epub 2021 Apr 9.

Council for Nutritional and Environmental Medicine, Mo i Rana, Norway. Electronic address:

Worldwide, scientists are looking for specific treatment for COVID-19. Apart from the antiviral approach, the interventions to support healthy immune responses to the virus are feasible through diet, nutrition, and lifestyle approaches. This narrative review explores the recent studies on dietary, nutritional, and lifestyle interventions that influence the microbiota-mediated immunomodulatory effects against viral infections. Read More

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Influence of postoperative radiotherapy target volumes in unilateral head and neck carcinoma of unknown primary: a multicentric study using propensity score.

Radiother Oncol 2021 Apr 9. Epub 2021 Apr 9.

Oncologic Surgery Department, Centre Léon Bérard, Lyon. Electronic address:

Objective: To compare the impact of two radiation modalities on loco-regional control, survival and tumour emergence, after node dissection for an unilateral head and neck carcinoma of unknown primary (HNCUP).

Materials And Methods: This is a multicentric retrospective study of 138 patients with unilateral HNCUP treated between 2002 and 2017. The absence of primary tumour was assessed by a systematic panendoscopy and positron emission tomography. Read More

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Energetic constraints imposed on trophic interaction strengths enhance resilience in empirical and model food webs.

J Anim Ecol 2021 Apr 12. Epub 2021 Apr 12.

Institute of Biochemistry and Biology, University of Potsdam, 14469, Potsdam, Germany.

Food web stability and resilience are at the heart of understanding the structure and functioning of ecosystems. Previous studies show that models of empirical food webs are substantially more stable than random ones, due to a few strong interactions embedded in a majority of weak interactions. Analyses of trophic interaction loops show that in empirical food webs the patterns in the interaction strengths prevent the occurrence of destabilizing heavy loops and thereby enhances resilience. Read More

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A Model-based Analysis of Supraspinal Mechanisms of Inter-leg Coordination in Human Gait: Toward Model-informed Robot-assisted Rehabilitation.

IEEE Trans Neural Syst Rehabil Eng 2021 Apr 12;PP. Epub 2021 Apr 12.

Stroke survivors are often left suffering from gait instability due to hemiparesis. This gait dysfunction can lead to higher fall rates and an overall decrease in quality of life. Though there are many post-stroke gait rehabilitation methods in use currently, none of them allow patients to regain complete functionality. Read More

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Proteome analysis of human adipocytes identifies depot-specific heterogeneity at metabolic control points.

Am J Physiol Endocrinol Metab 2021 Apr 12. Epub 2021 Apr 12.

Anatomy and Physiology, University of Melbourne, Australia.

Adipose tissue is a primary regulator of energy balance and metabolism. The distribution of adipose tissue depots is of clinical interest because the accumulation of upper-body subcutaneous (ASAT) and visceral adipose tissue (VAT) is associated with cardiometabolic diseases, whereas lower-body gluteal-femoral adipose tissue (GFAT) appears to be protective. There is heterogeneity in morphology and metabolism of adipocytes obtained from different regions of the body, but detailed knowledge of the constituent proteins in each depot is lacking. Read More

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Antibiotic Therapy and the Gut Microbiome: Investigating the Effect of Delivery Route on Gut Pathogens.

ACS Infect Dis 2021 Apr 12. Epub 2021 Apr 12.

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, U.K., BT9 7BL.

The contribution of the gut microbiome to human health has long been established, with normal gut microbiota conferring protection against invasive pathogens. Antibiotics can disrupt the microbial balance of the gut, resulting in disease and the development of antimicrobial resistance. The effect of antibiotic administration route on gut dysbiosis remains under-studied to date, with conflicting evidence on the differential effects of oral and parenteral delivery. Read More

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Gender Differences and Influencing Factors in Specialty Choices: Findings From One Medical School in China.

Front Public Health 2021 26;9:648612. Epub 2021 Mar 26.

Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China.

Gender plays a significant role in the selection of medical specialty. Few studies have been conducted to explore the impact of gender differences on specialty choosing among Chinese medical students. The specialty choices of 648 students from six consecutive classes in an 8-year MD program were collected and compared between male and female students. Read More

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Sex and Age Comparisons in Neuromuscular And Biomechanical Characteristics of the Knee in Young Athletes.

Int J Sports Phys Ther 2021 Apr 1;16(2):438-449. Epub 2021 Apr 1.

Atrium Health Musculoskeletal Institute.

Background: The identification of risk factors for injury is a key step for musculoskeletal injury prevention in youth sports. Not identifying and correcting for injury risk factors may result in lost opportunity for athletic development. Physical maturation and sex affect these characteristics, which may indicate the need for both age and sex-based injury prevention programs. Read More

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The Impact of Dance-Specific Neuromuscular Conditioning and Injury Prevention Training on Motor Control, Stability, Balance, Function and Injury in Professional Ballet Dancers: A Mixed-Methods Quasi-Experimental Study.

Int J Sports Phys Ther 2021 Apr 2;16(2):404-417. Epub 2021 Apr 2.

Cleveland State University.

Background: Professional ballet dancers suffer high injury rates and are less likely than other athletes to specifically train to improve muscular strength, coordination, agility, speed and motor control because of heavy training demands, aesthetic appearances and financial barriers.

Hypothesis/purpose: The purpose of this study was to examine the effects of a supplemental conditioning program on professional and pre-professional contemporary ballet dancers. The authors hypothesized that those participating in a training program would reduce injury rate by improving their motor control, stability, balance and physical function. Read More

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Lower Extremity Kinematics of the Y-Balance Test in Healthy and ACL Injured Adolescent Females.

Int J Sports Phys Ther 2021 Apr 1;16(2):381-392. Epub 2021 Apr 1.

University of Manitoba; Pan Am Clinic.

Background: Adolescent females are at significant risk for sustaining an ACL injury. The Y-Balance Test (YBT) is frequently used to evaluate neuromuscular control and lower extremity function. However, few studies have quantified 2D lower extremity kinematics during performance of the YBT, and there is an absence of kinematic data specific to at-risk adolescent females. Read More

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Temperature but not ocean acidification affects energy metabolism and enzyme activities in the blue mussel, .

Ecol Evol 2021 Apr 5;11(7):3366-3379. Epub 2021 Mar 5.

Department of Biological Sciences University of North Carolina at Charlotte Charlotte NC USA.

In mosaic marine habitats, such as intertidal zones, ocean acidification (OA) is exacerbated by high variability of pH, temperature, and biological CO production. The nonlinear interactions among these drivers can be context-specific and their effect on organisms in these habitats remains largely unknown, warranting further investigation.We were particularly interested in (the blue mussel) from intertidal zones of the Gulf of Maine (GOM), USA, for this study. Read More

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Revisiting Pleiotropic Effects of Type I Interferons: Rationale for Its Prophylactic and Therapeutic Use Against SARS-CoV-2.

Front Immunol 2021;12:655528. Epub 2021 Mar 26.

Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Havana, Cuba.

The pandemic distribution of SARS-CoV-2 together with its particular feature of inactivating the interferon-based endogenous response and accordingly, impairing the innate immunity, has become a challenge for the international scientific and medical community. Fortunately, recombinant interferons as therapeutic products have accumulated a long history of beneficial therapeutic results in the treatment of chronic and acute viral diseases and also in the therapy of some types of cancer. One of the first antiviral treatments during the onset of COVID-19 in China was based on the use of recombinant interferon alfa 2b, so many clinicians began to use it, not only as therapy but also as a prophylactic approach, mainly in medical personnel. Read More

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The Effects of a 10-Week Neuromuscular Training on Postural Control in Elite Youth Competitive Ballroom Dancers: A Randomized Controlled Trial.

Front Physiol 2021 25;12:636209. Epub 2021 Mar 25.

Arts School, Beijing Sport University, Beijing, China.

The purpose of this randomized controlled trial was to evaluate the efficacy of a 10-week neuromuscular training (NMT) program on the postural control of elite youth competitive ballroom dancers. Forty-two dancers (21 couples) were randomly assigned to either the NMT group ( = 22) or the control group (CG; = 20). Participants in NMT underwent a three-sessions-per-week NMT program for 10 weeks. Read More

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Deletion of BDNF in Pax2 Lineage-Derived Interneuron Precursors in the Hindbrain Hampers the Proportion of Excitation/Inhibition, Learning, and Behavior.

Front Mol Neurosci 2021 26;14:642679. Epub 2021 Mar 26.

Department of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Molecular Physiology of Hearing, University of Tübingen, Tübingen, Germany.

Numerous studies indicate that deficits in the proper integration or migration of specific GABAergic precursor cells from the subpallium to the cortex can lead to severe cognitive dysfunctions and neurodevelopmental pathogenesis linked to intellectual disabilities. A different set of GABAergic precursors cells that express Pax2 migrate to hindbrain regions, targeting, for example auditory or somatosensory brainstem regions. We demonstrate that the absence of BDNF in Pax2-lineage descendants of KOs causes severe cognitive disabilities. Read More

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Self-reported socket comfort, mobility, and balance-confidence of individuals with transtibial amputation using pinlock vs suction suspension.

J Dev Behav Pediatr 2021 Apr 5. Epub 2021 Apr 5.

Department of Physical Therapy, University of Delaware, Newark, DE Independence Prosthetics-Orthotics, Inc., Newark, DE Christiana Spine Center, Newark, DE.

Background: Improper suspension between the residual limb and prosthesis can result in pistoning, which may compromise skin integrity and reduce overall user comfort. In addition to objective measures of limb pistoning, user perspective may provide insight into suspension system effectiveness.

Objectives: The primary objective of this analysis was to explore differences in self-reported measures among adults with transtibial amputation (TTA) using pinlock vs suction suspension systems. Read More

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Governance and groundwater modelling: Hints to boost the implementation of the EU Nitrate Directive. The Lombardy Plain case, N Italy.

Sci Total Environ 2021 Mar 27;782:146800. Epub 2021 Mar 27.

Department of Earth and Environmental Sciences, University of Pavia, Via Ferrata 1, 27100 Pavia, Italy.

The EU Nitrate Directive has been ruling for almost 30 years, nevertheless nitrate concentration in the Lombardy Plain did not decrease. Together with failures of management implementation, a possible cause for such field observations is that management actions were taken without adequately considering the actual hydrogeological dynamics. To consider this aspect, the paper presents a groundwater flow and transport numerical model of a specific area of the Lombardy Plain. Read More

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On the potential of ROI imaging in x-ray CT - a comparison of novel dynamic beam attenuators with current technology.

Med Phys 2021 Apr 10. Epub 2021 Apr 10.

Siemens Healthcare GmbH, Siemensstr. 3, 91301, Forchheim, Germany.

Purpose: In this work, we explore the potential of region-of-interest (ROI) imaging in x-ray computed tomography (CT). Using two dynamic beam attenuator (DBA) concepts for fluence field modulation (FFM) previously developed, we investigate and evaluate the potential dose savings in comparison with current FFM technology.

Methods: ROI imaging is a special application of FFM where the bulk of x-ray radiation is propagated toward a certain anatomical target (ROI), specified by the imaging task, while the surrounding tissue is spared from radiation. Read More

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Cell-type-specific synaptic imbalance and disrupted homeostatic plasticity in cortical circuits of ASD-associated Chd8 haploinsufficient mice.

Mol Psychiatry 2021 Apr 9. Epub 2021 Apr 9.

Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Heterozygous mutation of chromodomain helicase DNA binding protein 8 (CHD8) is strongly associated with autism spectrum disorder (ASD) and results in dysregulated expression of neurodevelopmental and synaptic genes during brain development. To reveal how these changes affect ASD-associated cortical circuits, we studied synaptic transmission in the prefrontal cortex of a haploinsufficient Chd8 mouse model. We report profound alterations to both excitatory and inhibitory synaptic transmission onto deep layer projection neurons, resulting in a reduced excitatory:inhibitory balance, which were found to vary dynamically across neurodevelopment and result from distinct effects of reduced Chd8 expression within individual neuronal subtypes. Read More

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Crosstalk between MUC1 and VEGF in angiogenesis and metastasis: a review highlighting roles of the MUC1 with an emphasis on metastatic and angiogenic signaling.

Cancer Cell Int 2021 Apr 9;21(1):200. Epub 2021 Apr 9.

Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, No. 146, South Gandhi Ave., Vanak Sq., Tehran, Iran.

VEGF and its receptor family (VEGFR) members have unique signaling transduction system that play significant roles in most pathological processes, such as angiogenesis in tumor growth and metastasis. VEGF-VEGFR complex is a highly specific mitogen for endothelial cells and any de-regulation of the angiogenic balance implicates directly in endothelial cell proliferation and migration. Moreover, it has been shown that overexpressing Mucin 1 (MUC1) on the surface of many tumor cells resulting in upregulation of numerous signaling transduction cascades, such as growth and survival signaling pathways related to RTKs, loss of cell-cell and cell-matrix adhesion, and EMT. Read More

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FGF-MAPK signaling regulates human deep-layer corticogenesis.

Stem Cell Reports 2021 Mar 30. Epub 2021 Mar 30.

The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC 3010, Australia.

Despite heterogeneity across the six layers of the mammalian cortex, all excitatory neurons are generated from a single founder population of neuroepithelial stem cells. However, how these progenitors alter their layer competence over time remains unknown. Here, we used human embryonic stem cell-derived cortical progenitors to examine the role of fibroblast growth factor (FGF) and Notch signaling in influencing cell fate, assessing their impact on progenitor phenotype, cell-cycle kinetics, and layer specificity. Read More

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Implementation of a Software Distribution Intervention to Improve Workload Balance in an Academic Pediatric Radiology Department.

J Digit Imaging 2021 Apr 9. Epub 2021 Apr 9.

Texas Children's Hospital, Singleton Department of Pediatric Radiology, 6107 Fannin Street, Suite 470, 77030, Houston, TX, USA.

In our pediatric radiology department, radiographs (XR) are the shared responsibility of the body section and interpreted in addition to modality or site-specific assignments. Given an unequal contribution amongst radiologists to the XR workload, a software solution was developed to distribute radiographs and improve workload balance. Metrics to evaluate the intervention's effectiveness were compared before and after the intervention. Read More

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Epigenetic regulations in mammalian spermatogenesis: RNA-mA modification and beyond.

Cell Mol Life Sci 2021 Apr 9. Epub 2021 Apr 9.

Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Emerging evidence shows that mA, one of the most abundant RNA modifications in mammals, is involved in the entire process of spermatogenesis, including mitosis, meiosis, and spermiogenesis. "Writers" catalyze mA formation on stage-specific transcripts during male germline development, while "erasers" remove mA modification to maintain a balance between methylation and demethylation. The different functions of RNA-mA transcripts depend on their recognition by "readers". Read More

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Well-being Therapy in Depressive Disorders.

Adv Exp Med Biol 2021 ;1305:351-374

Department of Health Sciences, University of Florence, Florence, Italy.

A specific brief psychotherapeutic intervention aimed at empowering psychological well-being, the so-called Well-Being Therapy (WBT), has been manualized in 2016 by Giovanni Fava and has shown to be effective in randomized controlled trials. WBT is based on the multidimensional model of psychological well-being developed by Marie Jahoda which encompasses environmental mastery, personal growth, purpose in life, autonomy, self-acceptance, positive relations with others, and balance of psychic forces. WBT aims at promoting the achievement of an optimal-balanced functioning between the dimensions of psychological well-being, and such a balance is subsumed under the rubric of euthymia. Read More

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DEEPsc: A Deep Learning-Based Map Connecting Single-Cell Transcriptomics and Spatial Imaging Data.

Front Genet 2021 23;12:636743. Epub 2021 Mar 23.

Department of Mathematics, University of California, Irvine, Irvine, CA, United States.

Single-cell RNA sequencing (scRNA-seq) data provides unprecedented information on cell fate decisions; however, the spatial arrangement of cells is often lost. Several recent computational methods have been developed to impute spatial information onto a scRNA-seq dataset through analyzing known spatial expression patterns of a small subset of genes known as a reference atlas. However, there is a lack of comprehensive analysis of the accuracy, precision, and robustness of the mappings, along with the generalizability of these methods, which are often designed for specific systems. Read More

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A Novel Grape-Derived Prebiotic Selectively Enhances Abundance and Metabolic Activity of Butyrate-Producing Bacteria in Faecal Samples.

Front Microbiol 2021 23;12:639948. Epub 2021 Mar 23.

Department of Biology, University of Girona, Girona, Spain.

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) patients have different faecal microbiota profiles compared to healthy controls. Prebiotics intake influences intestinal microbiota composition which in turn influence the growth of short-chain fatty acids (SCFA) producing bacteria. This study aimed to evaluate the capacity of Previpect, a new prebiotic obtained from grapes fibre, to balance the dysbiosis found in patients with intestinal disorders. Read More

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A model and test for coordinated polygenic epistasis in complex traits.

Proc Natl Acad Sci U S A 2021 Apr;118(15)

Department of Neurology, University of California Los Angeles, Los Angeles, CA 90095;

Interactions between genetic variants-epistasis-is pervasive in model systems and can profoundly impact evolutionary adaption, population disease dynamics, genetic mapping, and precision medicine efforts. In this work, we develop a model for structured polygenic epistasis, called coordinated epistasis (CE), and prove that several recent theories of genetic architecture fall under the formal umbrella of CE. Unlike standard epistasis models that assume epistasis and main effects are independent, CE captures systematic correlations between epistasis and main effects that result from pathway-level epistasis, on balance skewing the penetrance of genetic effects. Read More

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