15,215 results match your criteria altering normal

Quantum Dot Labeling and Visualization of Extracellular Vesicles.

ACS Appl Nano Mater 2020 Jul 15;3(7):7211-7222. Epub 2020 Jun 15.

Molecular Engineering and Sciences Institute, Department of Chemical Engineering, Center on Human Development and Disability, and Department of Radiology, University of Washington, Seattle, Washington 98195-1652, United States.

Extracellular vesicles (EVs) are important mediators of intercellular communication. Their role in disease processes, uncovered mostly over the last two decades, makes them potential biomarkers, leading to a need to fundamentally understand EV biology. Direct visualization of EVs can provide insights into EV behavior, but current labeling techniques are often restricted by false-positive signals and rapid photobleaching. Read More

View Article and Full-Text PDF

IAMSE 2021-Plenary Session: Top 10 Ways an Instructional Designer Can Help You Define the New Normal.

Atsusi Hirumi

Med Sci Educ 2021 Sep 17:1-8. Epub 2021 Sep 17.

Department of Learning Sciences, University of Central Florida, Orlando, FL USA.

Along with the continued exponential growth of information and treatment options, healthcare practitioners must now deal with increasing documentation requirements, varying data systems, altering health plans, rising patient expectations, loss of autonomy, and demands to decrease costs while increasing revenue. Add to the complexity, the need to transform coursework and clinical experiences to address the constraints presented by COVID-19 can quickly overwhelm medical educators. Given such prodigious challenges, educational specialists with a solid understanding of learning research and theory, instructional design, and emerging technology can play a vital role in designing engaging learning experiences. Read More

View Article and Full-Text PDF
September 2021

The actin depolymerizing factor, Destrin, serves as a negative feedback inhibitor of smooth muscle cell differentiation.

Am J Physiol Heart Circ Physiol 2021 Sep 24. Epub 2021 Sep 24.

Department of Pathology and McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.

We have previously shown that several components of the RhoA signaling pathway control SMC phenotype by altering SRF-dependent gene expression. Because our genome wide analyses of chromatin structure and transcription factor binding suggested that the actin depolymerizing factor, DSTN, was regulated in a SMC-selective fashion, the goals of the current study were to identify the transcription mechanisms that control DSTN expression in SMC and to test whether it regulates SMC function. Immunohistochemical analyses revealed strong and at least partially SMC-selective expression of DSTN in many mouse tissues, a result consistent with human data from the GTEx consortium. Read More

View Article and Full-Text PDF
September 2021

Targeting the DNA damage response enhances CD70 CAR-T cell therapy for renal carcinoma by activating the cGAS-STING pathway.

J Hematol Oncol 2021 Sep 23;14(1):152. Epub 2021 Sep 23.

Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China.

Chimeric antigen receptor T-cell (CAR-T) therapy has shown tremendous success in eradicating hematologic malignancies. However, this success has not yet been extrapolated to solid tumors due to the limited infiltration and persistence of CAR-T cells in the tumor microenvironment (TME). In this study, we screened a novel anti-CD70 scFv and generated CD70 CAR-T cells that showed effective antitumor functions against CD70 renal carcinoma cells (RCCs) both in vitro and in vivo. Read More

View Article and Full-Text PDF
September 2021

[Restatment. Biological management of diabetes for patients with hemoglobinopathy].

Rev Prat 2021 Jun;71(6):653-658

Biologistes médicaux, laboratoire Laborizon Maine Anjou - Biogroup, Le Mans, France.

For a better biological management of diabetes for patients with hemoglobinopathy. Glycated hemoglobin, HbA1c, as a cumulative retrospective marker of glycemic control in diabetic patients could be faulty in patients with hemoglobinopathy. Abnormal hemoglobin could introduce bias analytically during HbA1c measure but also due to its physiopathology by altering the lifespan of red blood cells and/or the normal glycation process. Read More

View Article and Full-Text PDF

Implication of folate deficiency in CYP2U1 loss of function.

J Exp Med 2021 Nov 21;218(11). Epub 2021 Sep 21.

Department of Biochemistry and Molecular Biology, Hospices Civils de Lyon, Pierre Bénite, France.

Hereditary spastic paraplegias are heterogeneous neurodegenerative disorders. Understanding of their pathogenic mechanisms remains sparse, and therapeutic options are lacking. We characterized a mouse model lacking the Cyp2u1 gene, loss of which is known to be involved in a complex form of these diseases in humans. Read More

View Article and Full-Text PDF
November 2021

Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease.

Elife 2021 Sep 21;10. Epub 2021 Sep 21.

Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain.

Preadipocytes are crucial for healthy adipose tissue expansion. Preadipocyte differentiation is altered in obese individuals, which has been proposed to contribute to obesity-associated metabolic disturbances. Here, we aimed at identifying the pathogenic processes underlying impaired adipocyte differentiation in obese individuals with insulin resistance (IR)/type 2 diabetes (T2D). Read More

View Article and Full-Text PDF
September 2021

Structural variants are a major source of gene expression differences in humans and often affect multiple nearby genes.

Genome Res 2021 Sep 20. Epub 2021 Sep 20.

Yale School of Medicine

Structural variants (SVs) are an important source of human genome diversity but their functional effects are not well understood. We mapped 61,668 SVs in 613 individuals with deep genome sequencing data from the GTEx project and measured their effects on gene expression. We estimate that common SVs are causal at 2. Read More

View Article and Full-Text PDF
September 2021

Pivotal Roles for Ribonucleases in Streptococcus pneumoniae Pathogenesis.

mBio 2021 Sep 21:e0238521. Epub 2021 Sep 21.

Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center, Houston, Texas, USA.

RNases perform indispensable functions in regulating gene expression in many bacterial pathogens by processing and/or degrading RNAs. Despite the pivotal role of RNases in regulating bacterial virulence factors, the functions of RNases have not yet been studied in the major human respiratory pathogen Streptococcus pneumoniae (pneumococcus). Here, we sought to determine the impact of two conserved RNases, the endoribonuclease RNase Y and exoribonuclease polynucleotide phosphorylase (PNPase), on the physiology and virulence of S. Read More

View Article and Full-Text PDF
September 2021

Role of NELF-B in supporting epithelial-mesenchymal transition and cell proliferation during hepatocellular carcinoma progression.

Oncol Lett 2021 Nov 6;22(5):761. Epub 2021 Sep 6.

Department of Biotechnology, School of Sciences and Engineering, The American University in Cairo, New Cairo 11835, Egypt.

Negative elongation factor-B (NELF-B), also known as cofactor of BRCA1 (COBRA1), is one of the four subunits of the NELF complex. It interacts with BRCA1, in addition to other transcription complexes in various tissues. The NELF complex represses the transcription of several genes by stalling RNA polymerase II during the early phase of transcription elongation. Read More

View Article and Full-Text PDF
November 2021

Fundamentals of OA. An initiative of Osteoarthritis and Cartilage. Chapter 9: Obesity and metabolic factors in OA.

Osteoarthritis Cartilage 2021 Sep 16. Epub 2021 Sep 16.

Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA, 73104; Reynolds Oklahoma Center on Aging, Department of Biochemistry and Molecular Biology, Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA, 73104; Veterans Affairs Medical Center, Oklahoma City, OK, USA, 73104. Electronic address:

Objective: Obesity was once considered a risk factor for knee osteoarthritis (OA) primarily for biomechanical reasons. Here we provide an additional perspective by discussing how obesity also increases OA risk by altering metabolism and inflammation.

Design: This narrative review is presented in four sections: 1) metabolic syndrome and OA, 2) metabolic biomarkers of OA, 3) evidence for dysregulated chondrocyte metabolism in OA, and 4) metabolic inflammation: joint tissue mediators and mechanisms. Read More

View Article and Full-Text PDF
September 2021

Insm1, Neurod1, and Pax6 promote murine pancreatic endocrine cell development through overlapping yet distinct RNA transcription and splicing programs.

G3 (Bethesda) 2021 Aug 26. Epub 2021 Aug 26.

Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA.

Insm1, Neurod1, and Pax6 are essential for the formation and function of pancreatic endocrine cells. Here, we report comparative immunohistochemical, transcriptomic, functional enrichment, and RNA splicing analyses of these genes using gene knock-out mice. Quantitative immunohistochemical analysis confirmed that elimination of each of these three factors variably impairs the proliferation, survival, and differentiation of endocrine cells. Read More

View Article and Full-Text PDF

Biological Functions Driven by mRNAs Carried by Extracellular Vesicles in Cancer.

Front Cell Dev Biol 2021 30;9:620498. Epub 2021 Aug 30.

Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.

Extracellular vesicles (EVs), including exosomes and microvesicles, are extracellular nanovesicles released by most cells. EVs play essential roles in intercellular communication the transport of a large variety of lipids, proteins, and nucleic acids to recipient cells. Nucleic acids are the most commonly found molecules inside EVs, and due to their small size, microRNAs and other small RNAs are the most abundant nucleic acids. Read More

View Article and Full-Text PDF

Single-molecule force spectroscopy reveals structural differences of heparan sulfate chains during binding to vitronectin.

Phys Rev E 2021 Aug;104(2-1):024409

Department of Biophysical Microstructures, Institute of Nuclear Physics, Polish Academy of Sciences, PL-31342 Kraków, Poland.

The syndecans represent an ongoing research field focused on their regulatory roles in normal and pathological conditions. The role of syndecans in cancer progression is well documented, implicating their importance in diagnosis and even proposing various potential cancer treatments. Thus, the characterization of the unbinding properties at the single-molecule level will appeal to their use as targets for therapeutics. Read More

View Article and Full-Text PDF

Bis(2-ethylhexyl)-tetrabromophthalate induces zebrafish obesity by altering the brain-gut axis and intestinal microbial composition.

Environ Pollut 2021 Sep 6;290:118127. Epub 2021 Sep 6.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.

Multiple environmental stressors, including chemicals termed obesogens, contribute to the susceptibility of organisms to obesity. Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), a novel brominated flame retardant, is an environmental contaminant that may disrupt lipid metabolism. However, the risk of TBPH leading to obesity remains unknown. Read More

View Article and Full-Text PDF
September 2021

Increasing Viscosity Helps Explain Locomotor Control in Swimming .

K Lutek E M Standen

Integr Org Biol 2021 10;3(1):obab024. Epub 2021 Aug 10.

Department of Biology, University of Ottawa, 30 Marie-Curie Private, Ottawa, ON K1N 6N5, Canada.

Locomotion relies on the successful integration of sensory information to adjust brain commands and basic motor rhythms created by central pattern generators. It is not clearly understood how altering the sensory environment impacts control of locomotion. In an aquatic environment, mechanical sensory feedback to the animal can be readily altered by adjusting water viscosity. Read More

View Article and Full-Text PDF

Near Complete Repair After Myocardial Infarction in Adult Mice by Altering the Inflammatory Response With Intramyocardial Injection of α-Gal Nanoparticles.

Front Cardiovasc Med 2021 25;8:719160. Epub 2021 Aug 25.

Department of Medicine, Rush University Medical Center, Chicago, IL, United States.

Neonatal mice, but not older mice, can regenerate their hearts after myocardial-infarction (MI), a process mediated by pro-reparative macrophages. α-Gal nanoparticles applied to skin wounds in adult-mice bind the anti-Gal antibody, activate the complement cascade and generate complement chemotactic peptides that recruit pro-reparative macrophages which are further activated by these nanoparticles. The recruited macrophages decrease wound healing time by ~50%, restore the normal skin structure and prevent fibrosis and scar formation in mice. Read More

View Article and Full-Text PDF

Global gross nitrification rates are dominantly driven by soil carbon-to-nitrogen stoichiometry and total nitrogen.

Glob Chang Biol 2021 Sep 12. Epub 2021 Sep 12.

Institute of Plant Ecology (IFZ), Justus Liebig University Giessen, Giessen, Germany.

Soil gross nitrification (GN) is a critical process in the global nitrogen (N) cycle that results in the formation of nitrate through microbial oxidation of ammonium or organic N, and can both increase N availability to plants and nitrous oxide emissions. Soil GN is thought to be mainly controlled by soil characteristics and the climate, but a comprehensive analysis taking into account the climate, soil characteristics, including microbial characteristics, and their interactions to better understand the direct and indirect controlling factors of GN rates globally is lacking. Using a global meta-analysis based on 901 observations from 330 N-labeled studies, we show that GN differs significantly among ecosystem types, with the highest rates found in croplands, in association with higher pH which stimulates nitrifying bacteria activities. Read More

View Article and Full-Text PDF
September 2021

Liubao brick tea activates the PI3K-Akt signaling pathway to lower blood glucose, metabolic disorders and insulin resistance via altering the intestinal flora.

Food Res Int 2021 Oct 10;148:110594. Epub 2021 Jul 10.

Institute of Food Engineering, College of Life Sciences, Shanghai Normal University, 100 Guilin Road, Xuhui District, Shanghai 200234, China. Electronic address:

Diabetes and its related metabolic disorders are worldwide public health issues. Many studies have shown that changes in the structure and composition of the intestinal flora are closely related to the host's physiological and pathological processes. In this study, we aim to explore the effect of Liubao tea (LBT) extract on hyperglycemic mice with metabolic disorders and intestinal flora dysbiosis and to further study its regulatory effect on insulin resistance and its potential regulatory mechanism. Read More

View Article and Full-Text PDF
October 2021

Somatic intronic TP53 c.375+5G mutations are a recurrent but under-recognized mode of TP53 inactivation.

J Pathol Clin Res 2021 Sep 10. Epub 2021 Sep 10.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

TP53 is one of the most ubiquitously altered genes in human cancer. The biological impact of rare variants, particularly those located within noncoding regions, remains poorly understood. From interrogation of clinical massively parallel sequencing data from over 55,000 tumors, which included 23,330 tumors with known TP53 mutations, TP53 intron 4 nucleotide substitutions at position c. Read More

View Article and Full-Text PDF
September 2021

Parameter Identification from Normal and Pathological Middle Ears Using a Tailored Parameter Identification Algorithm.

J Biomech Eng 2021 Sep 10. Epub 2021 Sep 10.

Reutlingen University, 72762 Reutlingen, Germany.

Current clinical practice is often unable to identify the causes of conductive hearing loss in the middle ear with sufficient certainty without exploratory surgery. Besides the large uncertainties due to interindividual variances, only partially understood cause-effect principles are a major reason for the hesitant use of objective methods such as wideband tympanometry in diagnosis, despite their high sensitivity to pathological changes. For a better understanding of objective metrics of the middle ear, this study presents a model that can be used to reproduce characteristic changes in metrics of the middle ear by altering local physical model parameters linked to the anatomical causes of a pathology. Read More

View Article and Full-Text PDF
September 2021

Protease Activated Receptors and Arthritis.

Int J Mol Sci 2021 Aug 28;22(17). Epub 2021 Aug 28.

Departments of Pharmacology and Anesthesia, Pain Management & Perioperative Medicine, Dalhousie University, 5850 College Street, Halifax, NS B3H 4R2, Canada.

The catabolic and destructive activity of serine proteases in arthritic joints is well known; however, these enzymes can also signal pain and inflammation in joints. For example, thrombin, trypsin, tryptase, and neutrophil elastase cleave the extracellular N-terminus of a family of G protein-coupled receptors and the remaining tethered ligand sequence then binds to the same receptor to initiate a series of molecular signalling processes. These protease activated receptors (PARs) pervade multiple tissues and cells throughout joints where they have the potential to regulate joint homeostasis. Read More

View Article and Full-Text PDF

Autofluorescence-spectral imaging as an innovative method for rapid, non-destructive and reliable assessing of soybean seed quality.

Sci Rep 2021 Sep 8;11(1):17834. Epub 2021 Sep 8.

Department of Biosystems Engineering, School of Sciences and Engineering, São Paulo State University (UNESP), Tupã, SP, 17602-496, Brazil.

In the agricultural industry, advances in optical imaging technologies based on rapid and non-destructive approaches have contributed to increase food production for the growing population. The present study employed autofluorescence-spectral imaging and machine learning algorithms to develop distinct models for classification of soybean seeds differing in physiological quality after artificial aging. Autofluorescence signals from the 365/400 nm excitation-emission combination (that exhibited a perfect correlation with the total phenols in the embryo) were efficiently able to segregate treatments. Read More

View Article and Full-Text PDF
September 2021

Patients with Moderate Non-Culprit Coronary Lesions of Recent Acute Coronary Syndrome.

Int Heart J 2021 Sep 7. Epub 2021 Sep 7.

Department of Cardiology, Bajcsy-Zsilinszky Hospital.

Fractional flow reserve (FFR) measurement was compared to dobutamine stress echocardiography (DSE) instable angina (SA) with stable coronary lesion (s) (SCL (s) ) in a few trials; however, similar comparisons in patients with acute coronary syndrome (ACS) with non-culprit lesion (s) (NCL (s) ) are lacking. Our objectives were to prospectively evaluate the diagnostic performance of FFR with two different cutoff values (< 0.80 and < 0. Read More

View Article and Full-Text PDF
September 2021

Loss of Autophagy Causes Increased Apoptosis of Tibial Plateau Chondrocytes in Guinea Pigs with Spontaneous Osteoarthritis.

Cartilage 2021 Sep 7:19476035211044820. Epub 2021 Sep 7.

Department of Orthopaedic Surgery, Shanxi Provincial People's Hospital, Taiyuan, China.

Objective: The goal of the present study was to observe the effect of autophagy in tibial plateau chondrocytes on apoptosis in spontaneous knee osteoarthritis (OA) in guinea pigs.

Design: Fifty 2-month-old female Hartley guinea pigs were divided into a normal group (10 animals, all euthanized after 7 months) and an OA group (40 animals, 10 of which were euthanized after 10 months). Immunohistochemistry, RT-qPCR and Western blotting were used to evaluate autophagy levels, intracellular glycogen accumulation and apoptosis in tibial plateau chondrocytes and . Read More

View Article and Full-Text PDF
September 2021

Real-world particulate matters induce lung toxicity in rats fed with a high-fat diet: Evidence of histone modifications.

J Hazard Mater 2021 08 23;416:126182. Epub 2021 May 23.

Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, 1799 Jimei Road, Xiamen 361021, China. Electronic address:

Exposure to ambient particulate matters (PMs) has been associated with a variety of lung diseases, and high-fat diet (HFD) was reported to exacerbate PM-induced lung dysfunction. However, the underlying mechanisms for the combined effects of HFD and PM on lung functions remain poorly unraveled. By performing a comparative proteomic analysis, the current study investigated the global changes of histone post-translational modifications (PTMs) in rat lung exposed to long-term, real-world PMs. Read More

View Article and Full-Text PDF

Kindlin-2 promoted the progression of keloids through the Smad pathway and Fas/FasL pathway.

Exp Cell Res 2021 Sep 4:112813. Epub 2021 Sep 4.

Department of Otorhinolaryngology Head and Neck Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address:

Keloids are benign skin tumors characterized by aggressive growth. To date, there is no exact treatment because little is known about its pathological mechanism. Therefore, it is important to investigate the mechanism of its occurrence and development to identify therapeutic targets. Read More

View Article and Full-Text PDF
September 2021

The Effects of Trained Innate Immunity on T Cell Responses; Clinical Implications and Knowledge Gaps for Future Research.

Front Immunol 2021 19;12:706583. Epub 2021 Aug 19.

Human and Translational Immunology Group, Department of Clinical Medicine, Trinity Translational Medicine Institute, St James's Hospital, Trinity College Dublin, The University of Dublin, Dublin, Ireland.

The burgeoning field of innate immune training, also called trained immunity, has given immunologists new insights into the role of innate responses in protection against infection and in modulating inflammation. Moreover, it has led to a paradigm shift in the way we think about immune memory and the interplay between innate and adaptive immune systems in conferring immunity against pathogens. Trained immunity is the term used to describe the medium-term epigenetic and metabolic reprogramming of innate immune cells in peripheral tissues or in the bone marrow stem cell niche. Read More

View Article and Full-Text PDF

Gene-teratogen interactions influence the penetrance of birth defects by altering Hedgehog signaling strength.

Development 2021 Sep 6. Epub 2021 Sep 6.

Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

Birth defects result from interactions between genetic and environmental factors, but the mechanisms remain poorly understood. We find that mutations and teratogens interact in predictable ways to cause birth defects by changing target cell sensitivity to Hedgehog (Hh) ligands. These interactions converge on a membrane protein complex, the MMM complex, that promotes degradation of the Hh transducer Smoothened (SMO). Read More

View Article and Full-Text PDF
September 2021

Effects of long-term consumption of sucralose associated with high-fat diet in male mice.

Food Funct 2021 Sep 6. Epub 2021 Sep 6.

Chemical, Biological and Agricultural Pluridisciplinary Research Center (CPQBA), State University of Campinas, Campinas, SP, Brazil.

Sucralose is a widely consumed non-nutritive sweetener (NNS). Studies have shown that some NNS can favor weight gain by altering the intestinal microbiota, satiety hormone production, or aspects related to glucose homeostasis. In this study, we investigated the effects of sucralose consumption in mice fed with normal or high-fat diet (HFD) for an extended period (16 weeks). Read More

View Article and Full-Text PDF
September 2021