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New methods to decrypt emerging macropinosome functions during the host-pathogen crosstalk.

Cell Microbiol 2021 Apr 13. Epub 2021 Apr 13.

Institut Pasteur, Dynamics of Host-Pathogen Interactions Unit and CNRS UMR 3691, Paris, France.

Large volumes of liquid and other material from the extracellular environment are internalized by eukaryotic cells via an endocytic process called macropinocytosis. It is now recognized that this fundamental and evolutionary conserved pathway is hijacked by numerous intracellular pathogens as entry portal to the host cell interior. Yet, an increasing number of additional cellular functions of macropinosomes in pathologic processes have been reported beyond this role for fluid internalization. Read More

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Cellular fate of intersex differentiation.

Cell Death Dis 2021 Apr 12;12(4):388. Epub 2021 Apr 12.

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Renmin Hospital of Wuhan University, Wuhan, China.

Infertile ovotestis (mixture of ovary and testis) often occurs in intersex individuals under certain pathological and physiological conditions. However, how ovotestis is formed remains largely unknown. Here, we report the first comprehensive single-cell developmental atlas of the model ovotestis. Read More

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Atlas of breast cancer infiltrated B-lymphocytes revealed by paired single-cell RNA-sequencing and antigen receptor profiling.

Nat Commun 2021 04 12;12(1):2186. Epub 2021 Apr 12.

National Institute of Biological Sciences, Beijing, China.

To gain mechanistic insights into the functions and developmental dynamics of tumor-infiltrated immune cells, especially B-lymphocytes, here we combine single-cell RNA-sequencing and antigen receptor lineage analysis to characterize a large number of triple-negative breast cancer infiltrated immune cells and report a comprehensive atlas of tumor-infiltrated B-lymphocytes. The single-cell transcriptional profiles reveal significant heterogeneity in tumor-infiltrated B-cell subgroups. The single-cell antigen receptor analyses demonstrate that compared with those in peripheral blood, tumor-infiltrated B-cells have more mature and memory B-cell characteristics, higher clonality, more class switching recombination and somatic hypermutations. Read More

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RNA Nanotechnology to Build a Dodecahedral Genome of Single-Stranded RNA Virus.

RNA Biol 2021 Apr 12. Epub 2021 Apr 12.

Center for RNA Nanobiotechnology and Nanomedicine, The Ohio State University, Columbus, OH, USA.

The quest for artificial RNA viral complexes with authentic structure while being non-replicative is on its way for the development of viral vaccines. RNA viruses contain capsid proteins that interact with the genome during morphogenesis. The sequence and properties of the protein and genome determine the structure of the virus. Read More

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NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2021.

J Natl Compr Canc Netw 2021 Apr 1;19(4):364-376. Epub 2021 Apr 1.

32National Comprehensive Cancer Network.

Over the past few years, the NCCN Guidelines for Melanoma: Cutaneous have been expanded to include pathways for treatment of microscopic satellitosis (added in v2.2020), and the following Principles sections: Molecular Testing (added in v2.2019), Systemic Therapy Considerations (added in v2. Read More

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UPLC-orbitrap-MS-based metabolic profiling of HaCaT cells exposed to withanolides extracted from Datura metel.L: Insights from an untargeted metabolomics.

J Pharm Biomed Anal 2021 Feb 16;199:113979. Epub 2021 Feb 16.

Heilongjiang University of Traditional Chinese Medicine, Heping Road 24, Harbin, 150040, China. Electronic address:

In recent decades, more and more attention to the withanolides extracted from Datura metel.L has been paid due to their anti-psoriatic effects. Withanolides have also been reported to exhibit anti-inflammatory and anti-proliferative properties. Read More

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February 2021

Phosphorylation of the LIR domain of SCOC modulates ATG8 binding affinity and specificity.

J Mol Biol 2021 Apr 9:166987. Epub 2021 Apr 9.

Molecular Cell Biology of Autophagy, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK; current address: Department of Molecular Cell Biology, Centre for Cancer Biomedicine, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0379 Oslo, Norway. Electronic address:

Autophagy is a highly conserved degradative pathway, essential for cellular homeostasis and implicated in diseases including cancer and neurodegeneration. Autophagy-related 8 (ATG8) proteins play a central role in autophagosome formation and selective delivery of cytoplasmic cargo to lysosomes by recruiting autophagy adaptors and receptors. The LC3-interacting region (LIR) docking site (LDS) of ATG8 proteins binds to LIR motifs present in autophagy adaptors and receptors. Read More

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Synthesis of C Chemicals from CO and H via C-C Bond Formation.

Acc Chem Res 2021 Apr 12. Epub 2021 Apr 12.

Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Colloid, Interface and Chemical Thermodynamics, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

ConspectusThe severity of global warming necessitates urgent CO mitigation strategies. Notably, CO is a cheap, abundant, and renewable carbon resource, and its chemical transformation has attracted great attention from society. Because CO is in the highest oxidation state of the C atom, the hydrogenation of CO is the basic means of converting it to organic chemicals. Read More

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The interplay between DNA and histone methylation: molecular mechanisms and disease implications.

EMBO Rep 2021 Apr 12:e51803. Epub 2021 Apr 12.

Department of Genetics and Development and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.

Methylation of cytosine in CpG dinucleotides and histone lysine and arginine residues is a chromatin modification that critically contributes to the regulation of genome integrity, replication, and accessibility. A strong correlation exists between the genome-wide distribution of DNA and histone methylation, suggesting an intimate relationship between these epigenetic marks. Indeed, accumulating literature reveals complex mechanisms underlying the molecular crosstalk between DNA and histone methylation. Read More

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On the function and relevance of alternative 3'-UTRs in gene expression regulation.

Wiley Interdiscip Rev RNA 2021 Apr 12:e1653. Epub 2021 Apr 12.

Gene Regulation, i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.

Messanger RNA (mRNA) isoforms with alternative 3'-untranslated regions (3'-UTRs) are produced by alternative polyadenylation (APA), which occurs during transcription in most eukaryotic genes. APA fine-tunes gene expression in a cell-type- and cellular state-dependent manner. Selection of an APA site entails the binding of core cleavage and polyadenylation factors to a particular polyadenylation site localized in the pre-mRNA and is controlled by multiple regulatory determinants, including transcription, pre-mRNA cis-regulatory sequences, and protein factors. Read More

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The recent 10-year landscape of aortic dissection research: a bibliometric analysis.

J Thorac Dis 2021 Mar;13(3):1592-1602

Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Background: We aimed to comprehensively analyze all the literature related to aortic dissection (AD) in the past decade using Web Scrapping technology from PubMed, revealing the research dynamics in this field.

Methods: Data were retrieved and downloaded from PubMed with search strategy as "(aortic dissection [Title/Abstract]) AND (2010[EDAT]: 2020[EDAT])". Information on the PMID, journal name, title, number of citations, publication year, authors, affiliations, abstract, study type, and keywords of the research was recorded. Read More

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Variants at the MHC Region Associate With Susceptibility to Infection: A Genome-Wide Association Study Using Comprehensive Electronic Health Records.

Front Immunol 2021 25;12:638913. Epub 2021 Mar 25.

Genomic Medicine Institute, Geisinger, Danville, PA, United States.

Background: is a major cause of healthcare-associated and community-acquired diarrhea. Host genetic susceptibility to infection has not been studied on a large-scale.

Methods: A total of 1,160 infection cases and 15,304 controls were identified by applying the eMERGE infection algorithm to electronic health record data. Read More

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How Negative Experience Influences the Brain: A Comprehensive Review of the Neurobiological Underpinnings of Nocebo Hyperalgesia.

Front Neurosci 2021 24;15:652552. Epub 2021 Mar 24.

Health, Medical & Neuropsychology Unit, Leiden University, Leiden, Netherlands.

This comprehensive review summarizes and interprets the neurobiological correlates of nocebo hyperalgesia in healthy humans. Nocebo hyperalgesia refers to increased pain sensitivity resulting from negative experiences and is thought to be an important variable influencing the experience of pain in healthy and patient populations. The young nocebo field has employed various methods to unravel the complex neurobiology of this phenomenon and has yielded diverse results. Read More

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Urine Metabolite Levels, Adverse Kidney Outcomes, and Mortality in CKD Patients: A Metabolome-wide Association Study.

Am J Kidney Dis 2021 Apr 8. Epub 2021 Apr 8.

Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of Freiburg, Hugstetter Str. 49, 79106 Freiburg, Germany. Electronic address:

Rationale & Objective: Mechanisms underlying the variable course of disease progression in patients with chronic kidney disease (CKD) are incompletely understood. The aim of this study was to identify novel biomarkers of adverse kidney outcomes and overall mortality, which may offer insights into pathophysiological mechanisms.

Study Design: Metabolome-wide association study. Read More

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Insights about interventions to address food insecurity in adults with type 2 diabetes: Valuable lessons from the stories of African Americans living in the inner city.

Patient Educ Couns 2021 Mar 31. Epub 2021 Mar 31.

Division of General Internal Medicine, Department of Medicine, Froedtert & The Medical College of Wisconsin, Milwaukee, WI, United States; Center for Advancing Population Science, Medical College of Wisconsin, Milwaukee, WI, United States. Electronic address:

Objectives: This qualitative study aimed to gain insight from the perspectives of food insecure African Americans living in an inner city regarding important diabetes intervention strategies and components.

Methods: Using a grounded theory approach, two focus groups (totaling 16 individuals) were conducted in Milwaukee, Wisconsin. Purposive, convenience sampling was used to identify food insecure adults with diabetes. Read More

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Understanding the cellular origin and progression of esophageal cancer using esophageal organoids.

Cancer Lett 2021 Apr 7. Epub 2021 Apr 7.

Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, USA; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA. Electronic address:

Three-dimensional (3D) organoids are a novel tool to model epithelial cell biology and human diseases of the esophagus. 3D organoid culture systems have been utilized to investigate the pathobiology of esophageal cancer, including both squamous cell carcinoma and adenocarcinoma. Additional organoid-based approaches for study of esophageal development and benign esophageal diseases have provided key insights into esophageal keratinocyte differentiation and mucosal regeneration. Read More

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Starch-lipid interaction alters the molecular structure and ultimate starch bioavailability: A comprehensive review.

Int J Biol Macromol 2021 Apr 7. Epub 2021 Apr 7.

Division of Biochemistry, ICAR - Indian Agricultural Research Institute (IARI), New Delhi 110012, India. Electronic address:

Starch bioavailability which results in eliciting postprandial glycaemic response, is a trait of great significance and is majorly influenced by the physical interaction among the matrix components governed by their molecular structure as well as dynamics. Among physical interactions limiting starch bioavailability, starch and any guest molecules like lipid interact together to alter the molecular structure into a compact V-type arrangement endorsing the processed crystallinity, thus limiting carbolytic enzymatic digestion and further bioavailability. Considering the importance of starch-lipid dynamics affecting bioavailability, intensive research based on endogenous (internal lipids which are embedded into the food matrix) as well as exogenous (those are added from outside into the food matrix during processing like cooking) lipids have been carried out, endorsing physical interactions at colloidal and microstructural levels. Read More

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Comprehensive Review of Cardiovascular Involvement in COVID-19.

AACN Adv Crit Care 2021 Apr 15:e1-e19. Epub 2021 Apr 15.

Ruff Joseph Macale Cajanding is Charge Nurse, Adult Critical Care Unit, 6th Floor, King George V Building, St. Bartholomew's Hospital, Barts Health NHS Trust, 2 King Edward Street, London EC1A 1HQ, United Kingdom

COVID-19 has emerged as one of the most devastating and clinically significant infectious diseases of the last decade. It has reached global pandemic status at an unprecedented pace and has placed significant demands on health care systems worldwide. Although COVID-19 primarily affects the lungs, epidemiologic reports have shown that the disease affects other vital organs of the body, including the heart, vasculature, kidneys, brain, and the hematopoietic system. Read More

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Migrant youths: Typical aspects of development during the adolescent years, specific challenges of growing up somewhere else, and some things we need to understand better.

Authors:
Peter Noack

New Dir Child Adolesc Dev 2021 Apr 9. Epub 2021 Apr 9.

Department of Psychology, Friedrich-Schiller-University of Jena, Jena, Germany.

The research presented in this Issue impressively documents the great variety of conditions of live that impact child and adolescent migrants' development. The studies conducted in various receiving countries include young refugees as well as the first- and second-generation offspring of migrant families who left their homes in different areas of the globe. Despite this diversity, theories and empirical findings on processes of normative development could be successfully applied, yielding insights into more general aspects of development At the same time, drawing on conceptualizations that were introduced to specifically address experiences and challenges linked to the situation of migrant and minority populations, such as ethnic identity or acculturation, the articles notably contributed to a more comprehensive understanding of migrant adolescents' lives. Read More

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Horizontally acquired cysteine synthase genes undergo functional divergence in lepidopteran herbivores.

Heredity (Edinb) 2021 Apr 8. Epub 2021 Apr 8.

College of Animal Sciences, Zhejiang University, Hangzhou, China.

Horizontal gene transfer (HGT) plays an important role in evolutionary processes as organisms adapt to their environments, and now cases of gene duplication after HGT in eukaryotes are emerging at an increasing rate. However, the fate and roles of the duplicated genes over time in eukaryotes remain unclear. Here we conducted a comprehensive analysis of the evolution of cysteine synthase (CYS) in lepidopteran insects. Read More

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Coming of age of allotrope: proceedings from the Fall 2020 Allotrope Connect.

Drug Discov Today 2021 Apr 5. Epub 2021 Apr 5.

Department of Physics and Astronomy, Brigham Young University, Provo, UT, USA. Electronic address:

The Allotrope Foundation (AF) is a group of pharmaceutical, device vendor, and software companies that develops and releases technologies [the Allotrope Data Format (ADF), the Allotrope Foundation Ontology (AFO), and the Allotrope Data Models (ADM)] to simplify the exchange of electronic data. We present here the first comprehensive history of the AF, its structure, a list of members and partners, and an introduction to the technologies. Finally, we provide current insights into the adoption and development of the technologies by summarizing the Fall 2020 Allotrope Connect virtual conference. Read More

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Integrated Analysis of mRNA-mA-protein Profiles Reveals Novel Insights into the Mechanisms for Cadmium-induced Urothelial Transformation.

Biomarkers 2021 Apr 8:1-23. Epub 2021 Apr 8.

Department of Geratology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, 510080.

This study aimed to investigate the mechanisms underlying Cd-induced urothelial transformation, using multi-omics analyses (transcriptome, epitranscriptome, and proteome). Transcriptomics analysis was performed to estimate the expression of genes, methylated RNA immunoprecipitation sequencing analysis was used to detect mA modification, while proteomics analysis was used to identify differentially expressed proteins. Differentially expressed genes (DEGs) were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Read More

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Effect of Stapling on the Thermodynamics of mdm2-p53 Binding.

J Chem Inf Model 2021 Apr 8. Epub 2021 Apr 8.

Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.

Protein-protein interaction (PPI) is one of the key regulatory features driving biomolecular processes and hence is targeted for designing therapeutics against diseases. Small peptides are a new and emerging class of therapeutics owing to their high specificity and low toxicity. For achieving efficient targeting of the PPI, amino acid side chains are often stapled together, resulting in the rigidification of these peptides. Read More

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A comprehensive characterization of ecological and epidemiological factors driving perennation of chasmothecia on hop ().

Phytopathology 2021 Apr 8. Epub 2021 Apr 8.

Cornell University, NYSAES, Plant Pathology, 630 W. North St, Geneva, New York, United States, 14456;

Hop powdery mildew, caused by the ascomycete fungus is a consistent threat to sustainable hop production. The pathogen utilizes two reproductive strategies for overwintering and perennation: (i) asexual vegetative hyphae on dormant buds that emerge the following season as infected shoots; and (ii) sexual ascocarps (chasmothecia), which are presumed to discharge ascospores during spring rain events. We demonstrate that chasmothecia, in the absence of any asexual growth forms, are a viable overwintering source capable of causing early season infection two to three orders of magnitude greater than that reported for perennation via asexual growth. Read More

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