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TRIM27 protects against cardiac ischemia-reperfusion injury by suppression of apoptosis and inflammation via negatively regulating p53.

Biochem Biophys Res Commun 2021 Apr 14;557:127-134. Epub 2021 Apr 14.

Department of General Medicine, The Sixth Annex Hospital of Xinjiang Medical University, Wulumuqi, 830002, China. Electronic address:

Myocardial ischemia/reperfusion (MI/R) has high morbidity and mortality worldwide, but the underlying mechanisms have not been entirely understood. TRIM27 is one of the Tri-domain proteins (TRIM) family proteins with crucial roles in numerous life processes. In the study, we attempted to explore the effects of heart-conditional knockout of TRIM27 (TRIM27) on MI/R progression both in vivo and in vitro. Read More

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Effect of chronic binge-like ethanol consumption on subsequent cocaine reinforcement in rhesus monkeys.

Drug Alcohol Depend 2021 Apr 10;223:108707. Epub 2021 Apr 10.

Department of Physiology & Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, United States. Electronic address:

Background: Although most individuals with cocaine use disorder also abuse alcohol, little is known about the behavioral and pharmacological mechanisms that promote co-abuse. For example, it is unclear whether prior experience with alcohol renders individuals more sensitive to cocaine when it is subsequently experienced.

Methods: This study examined the effects of chronic ethanol consumption on subsequent cocaine reinforcement in rhesus monkeys. Read More

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Caspase-3, a shrimp phosphorylated hemocytic protein is necessary to control YHV infection.

Fish Shellfish Immunol 2021 Apr 14. Epub 2021 Apr 14.

Institute of Molecular Biosciences, Mahidol University, Salaya Campus, Phutthamonthon 4 Rd, Salaya, Nakhon Pathom, 73170, Thailand. Electronic address:

By using immunohistochemistry detection, yellow head virus (YHV) was found to replicate in granule-containing hemocytes including semi-granular hemocytes (SGC) and granular hemocytes (GC) during the early phase (24 hours post injection) of YHV-infected shrimp. Higher signal of YHV infection was found in GC more than in SGC. Comparative phosphoproteomic profiles between YHV-infected and non-infected GC reveal a number of phosphoproteins with different expression levels. Read More

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Differences in growth of Trypanoplasma borreli in carp serum is dependent on transferrin genotype.

Fish Shellfish Immunol 2021 Apr 14. Epub 2021 Apr 14.

Polish Academy of Sciences, Institute of Ichthyobiology and Aquaculture in Gołysz, Zaborze, 43-520, Chybie, Poland. Electronic address:

Kinetoplastid parasites require transferrin (Tf), being the main source of iron, for growth and multiplication. This group of parasites developed a unique receptor-mediated system for acquiring host Tf which bears no structural homology with the host transferrin receptor. Trypanoplasma borreli, a blood parasite of common carp, probably uses a similar mechanism to sequester iron from host transferrin. Read More

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Cigarette smoke exposure causes systemic and autonomic cardiocirculatory changes in rats depending on the daily exposure dose.

Life Sci 2021 Apr 14:119498. Epub 2021 Apr 14.

Medical School, University of Ribeirão Preto, Ribeirão Preto, SP, Brazil. Electronic address:

Aims: To evaluate the systemic changes and autonomic cardiocirculatory control of awaken rats chronically exposed to the cigarette smoke (CS) of 1 or 2 cigarettes/day.

Main Methods: Rats were exposed to clean air (control) or cigarette smoke of 1 (CS1) or 2 (CS2) cigarettes/animal/day for 30 days. Then, arterial pressure (AP) and heart rate (HR) were recorded in conscious rats to assess spontaneous baroreflex sensitivity and HR and AP variabilities. Read More

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A Guide to time-resolved structural analysis of light-activated proteins.

FEBS J 2021 Apr 17. Epub 2021 Apr 17.

Manchester Institute of Biotechnology, Department of Chemistry, University of Manchester, 131 Princess Street, M1 7DN, Manchester, United Kingdom.

Dynamical changes in protein structures are essential for protein function and occur over femtoseconds to seconds timescales. X-ray free electron lasers have facilitated investigations of structural dynamics in proteins with unprecedented temporal and spatial resolution. Light-activated proteins are attractive targets for time-resolved structural studies, as the reaction chemistry and associated protein structural changes can be triggered by short laser pulses. Read More

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Repressors of anthocyanin biosynthesis.

New Phytol 2021 Apr 17. Epub 2021 Apr 17.

Department of Ecology and Evolutionary Biology, University of Connecticut, 75 North Eagleville Road, Storrs, CT, USA, 06269-3043.

Anthocyanins play a variety of adaptive roles in both vegetative tissues and reproductive organs of plants. The broad functionality of these compounds requires sophisticated regulation of the anthocyanin biosynthesis pathway to allow proper localization, timing, and optimal intensity of pigment deposition. While it is well-established that the committed steps of anthocyanin biosynthesis are activated by a highly conserved MYB-bHLH-WDR (MBW) protein complex in virtually all flowering plants, anthocyanin repression seems to be achieved by a wide variety of protein and small RNA families that function in different tissue types and in response to different developmental, environmental, and hormonal cues. Read More

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Heterochromatic Nonlinear Optical Responses in Upconversion Nanoparticles for Super-Resolution Nanoscopy.

Adv Mater 2021 Apr 17:e2008847. Epub 2021 Apr 17.

Institute for Biomedical Materials & Devices (IBMD), Faculty of Science, University of Technology Sydney, Sydney, NSW, 2007, Australia.

Point spread function (PSF) engineering by an emitter's response can code higher-spatial-frequency information of an image for microscopy to achieve super-resolution. However, complexed excitation optics or repetitive scans are needed, which explains the issues of low speed, poor stability, and operational complexity associated with the current laser scanning microscopy approaches. Here, the diverse emission responses of upconversion nanoparticles (UCNPs) are reported for super-resolution nanoscopy to improve the imaging quality and speed. Read More

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Subtle genomic DNA damage induces intraneuronal production of amyloid-β (1-42) by increasing β-secretase activity.

FASEB J 2021 May;35(5):e21569

Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.

Aberrant accumulation of amyloid-β (Aβ) in brain is the major trigger for pathogenesis in Alzheimer's disease (AD). It is imperative to understand how Aβ attains such toxic levels in the brain parenchyma. We detected that a subtle and tolerable amount of DNA damage, related to aging, increased intraneuronal Aβ production both in cultured neuron and in cortex of rodent brain. Read More

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Neural Correlates of Alcohol Use Disorder Severity among Non-Treatment Seeking Heavy Drinkers: An Examination of the Incentive Salience and Negative Emotionality Domains of the Alcohol and Addiction Research Domain Criteria.

Alcohol Clin Exp Res 2021 Apr 17. Epub 2021 Apr 17.

The Mind Research Network, Albuquerque, NM, USA.

Background: The Alcohol and Addiction Research Domain Criteria (AARDoC) proposes that alcohol use disorder is associated with neural dysfunction in three primary domains: incentive salience, negative emotionality, and executive function. Prior studies in heavy drinking samples have examined brain activation changes associated with alcohol and negative affect cues, representing the incentive salience and negative emotionality domains, respectively; yet studies examining such cue-induced changes in functional connectivity are relatively sparse.

Methods: Non-treatment seeking heavy drinking adults (N=149, 56. Read More

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Neuronal androgen receptor is required for activity dependent enhancement of peripheral nerve regeneration.

Dev Neurobiol 2021 Apr 17. Epub 2021 Apr 17.

Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA.

Neuronal activity after nerve injury can enhance axon regeneration and the restoration of function. The mechanism for this enhancement relies in part on hormone receptors, and we previously demonstrated that systemic androgen receptor antagonism blocked the effect of exercise or electrical stimulation on enhancing axon regeneration after nerve injury in both sexes. Here, we tested the hypothesis that the site of this androgen receptor signaling is both neuronal and involves the classical, genomic signaling pathway. Read More

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Magnetic Resonance Biomarkers in Radiation Oncology.

Med Phys 2021 Apr 17. Epub 2021 Apr 17.

Department of Radiation Oncology, Anderson Cancer Center, University of Texas, Houston, Texas, USA.

A magnetic resonance (MR) biologic marker (biomarker) is a measurable quantitative characteristic that is an indicator of normal biological and pathogenetic processes or a response to therapeutic intervention derived from the MR imaging process. There is significant potential for MR biomarkers to facilitate personalized approaches to cancer care through more precise disease targeting by quantifying normal versus pathologic tissue function as well as toxicity to both radiation and chemotherapy. Both of which have the potential to increase the therapeutic ratio and provide earlier, more accurate monitoring of treatment response. Read More

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Efficacy of Dupilumab for controlling severe atopic dermatitis with dominant-negative CARD11 variant.

Clin Exp Dermatol 2021 Apr 16. Epub 2021 Apr 16.

Dermatology department, Hôpital Saint-Louis, AP-HP, F-75010, Paris, France.

Hypomorphic dominant-negative mutations in Caspase Recruitment Domain-containing Protein 11 (CARD11) is a rare cause of severe atopic dermatitis. CARD11 is a membrane protein involved in TCR signalling via the NF-kB pathway that has been identified as a predisposition locus for severe atopy. A loss of function activity of CARD11 due to a dominant-negative effect of CARD11 variant leads to severe atopic dermatitis associated with a defective T cell response that polarize toward a Th2 phenotype. Read More

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The AT-1 Angiotensin Receptor is Involved in the Autonomic and Neuroendocrine Responses to Acute Restraint Stress in Male Rats.

Cell Mol Neurobiol 2021 Apr 16. Epub 2021 Apr 16.

Department of Pharmacology of the School of Medicine of Ribeirão Preto, University of São Paulo, Ave. Bandeirantes, São Paulo, Ribeirão Preto, 3900-14049-900, Brazil.

The renin-angiotensin system (RAS) is involved in cardiovascular and hydroelectrolytic control, being associated with the development of hypertension. The restraint stress (RS) model is an aversive situation, which promotes a sustained increase in blood pressure and heart rate, and stimulation of the hypothalamic-pituitary-adrenal axis. Stress leads to an increase of angiotensin-II contents both in the circulation and the central nervous system (CNS), as well as an increased expression of AT-1 receptors in CNS structures related to stress. Read More

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Short-, medium-, and long-chain fatty acid profiles and signaling is responsive to dietary phytase and lactic acid treatment of cereals along the gastrointestinal tract of growing pigs.

J Anim Sci 2021 Apr 17. Epub 2021 Apr 17.

Institute of Animal Nutrition and Functional Plant Compounds, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.

Dietary and microbially derived fatty acids (FA) play important roles in gut mucosal inflammatory signaling, barrier function and oxidative stress response. Nevertheless, little information is available about gastrointestinal FA profiles and receptor distribution in pigs, especially for long-chain FA (LCFA). Therefore, the present pilot study aimed to 1) investigate the gastrointestinal FA profiles; 2) link the luminal FA profiles to the mucosal expression of genes related to FA sensing and signaling; and 3) assess potential dietary effects on gut and systemic lipid metabolism in pigs. Read More

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Meclofenamate causes loss of cellular tethering and decoupling of functional networks in glioblastoma.

Neuro Oncol 2021 Apr 17. Epub 2021 Apr 17.

Translational NeuroOncology Research Group, Medical Center University of Freiburg, Germany.

Background: Glioblastoma cells assemble to a syncytial communicating network based on tumor microtubes (TMs) as ultra-long membrane protrusions. The relationship between network architecture and transcriptional profile remains poorly investigated. Drugs that interfere within this syncytial connectivity such as meclofenamate (MFA) may be highly attractive for glioblastoma therapy. Read More

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Loss of activating transcription factor 3 prevents KRAS-mediated pancreatic cancer.

Oncogene 2021 Apr 16. Epub 2021 Apr 16.

Children's Health Research Institute, London, ON, Canada.

The unfolded protein response (UPR) is activated in pancreatic pathologies and suggested as a target for therapeutic intervention. In this study, we examined activating transcription factor 3 (ATF3), a mediator of the UPR that promotes acinar-to-ductal metaplasia (ADM) in response to pancreatic injury. Since ADM is an initial step in the progression to pancreatic ductal adenocarcinoma (PDAC), we hypothesized that ATF3 is required for initiation and progression of PDAC. Read More

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Scopolamine promotes neuroinflammation and delirium-like neuropsychiatric disorder in mice.

Sci Rep 2021 Apr 16;11(1):8376. Epub 2021 Apr 16.

Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Postoperative delirium is a common neuropsychiatric syndrome resulting a high postsurgical mortality rate and decline in postdischarge function. Extensive research has been performed on both human and animal delirium-like models due to their clinical significance, focusing on systematic inflammation and consequent neuroinflammation playing a key role in the pathogenesis of postoperative cognitive dysfunctions. Since animal models are widely utilized for pathophysiological study of neuropsychiatric disorders, this study aimed at examining the validity of the scopolamine-induced delirium-like mice model with respect to the neuroinflammatory hypothesis of delirium. Read More

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Mitochondrial hydrogen peroxide positively regulates neuropeptide secretion during diet-induced activation of the oxidative stress response.

Nat Commun 2021 Apr 16;12(1):2304. Epub 2021 Apr 16.

Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Mitochondria play a pivotal role in the generation of signals coupling metabolism with neurotransmitter release, but a role for mitochondrial-produced ROS in regulating neurosecretion has not been described. Here we show that endogenously produced hydrogen peroxide originating from axonal mitochondria (mtHO) functions as a signaling cue to selectively regulate the secretion of a FMRFamide-related neuropeptide (FLP-1) from a pair of interneurons (AIY) in C. elegans. Read More

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Selective AKT kinase inhibitor capivasertib in combination with fulvestrant in PTEN-mutant ER-positive metastatic breast cancer.

NPJ Breast Cancer 2021 Apr 16;7(1):44. Epub 2021 Apr 16.

Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Five to ten percent of ER+ metastatic breast cancer (MBC) tumors harbor somatic PTEN mutations. Loss of function of this tumor-suppressor gene defines a highly aggressive, treatment-refractory disease for which new therapies are urgently needed. This Phase I multipart expansion study assessed oral capivasertib with fulvestrant in patients with PTEN-mutant ER+ MBC. Read More

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Global phosphoproteomics reveals DYRK1A regulates CDK1 activity in glioblastoma cells.

Cell Death Discov 2021 Apr 16;7(1):81. Epub 2021 Apr 16.

Charles Perkins Centre and School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, 2006, Australia.

Both tumour suppressive and oncogenic functions have been reported for dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). Herein, we performed a detailed investigation to delineate the role of DYRK1A in glioblastoma. Our phosphoproteomic and mechanistic studies show that DYRK1A induces degradation of cyclin B by phosphorylating CDC23, which is necessary for the function of the anaphase-promoting complex, a ubiquitin ligase that degrades mitotic proteins. Read More

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NF-κB blockade with oral administration of dimethylaminoparthenolide, delays prostate cancer resistance to androgen receptor inhibition and inhibits AR variants.

Mol Cancer Res 2021 Apr 16. Epub 2021 Apr 16.

Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute

NF-κB activation has been linked to prostate cancer (PCa) progression and is commonly observed in castrate-resistant disease. It has been suggested that NF-κB-driven resistance to androgen deprivation therapy (ADT) in PCa cells may be mediated by aberrant androgen receptor (AR) activation and AR splice variant production. Preventing resistance to ADT may therefore be achieved by utilizing NF-κB inhibitors. Read More

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Metabolomic Profiles in the Intestine of Shrimp Infected by White Spot Syndrome Virus and Antiviral Function of the Metabolite Linoleic Acid in Shrimp.

J Immunol 2021 Apr 16. Epub 2021 Apr 16.

Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, Shandong, China; and

White spot syndrome virus (WSSV) is a threatening pathogenic virus in shrimp culture, and at present, no effective strategy can prevent and control the disease. Intestinal flora and its metabolites are important for the resistance of shrimp to lethal pathogenic viruses. However, the changes of metabolites in the shrimp intestines after WSSV infection remain unclear. Read More

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Kdm6b Regulates the Generation of Effector CD8 T Cells by Inducing Chromatin Accessibility in Effector-Associated Genes.

J Immunol 2021 Apr 16. Epub 2021 Apr 16.

Center for Cancer Cell Biology, Immunology and Infection, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL;

The transcriptional and epigenetic regulation of CD8 T cell differentiation is critical for balancing pathogen eradication and long-term immunity by effector and memory CTLs, respectively. In this study, we demonstrate that the lysine demethylase 6b (Kdm6b) is essential for the proper generation and function of effector CD8 T cells during acute infection and tumor eradication. We found that cells lacking Kdm6b (by either T cell-specific knockout mice or knockdown using short hairpin RNA strategies) show an enhanced generation of memory precursor and early effector cells upon acute viral infection in a cell-intrinsic manner. Read More

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Loss of KCNQ2 or KCNQ3 leads to multifocal time-varying activity in the neonatal forebrain .

eNeuro 2021 Apr 15. Epub 2021 Apr 15.

Dept. of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269, USA

Early neonatal epileptic encephalopathy represents a group of epilepsies often characterized by refractory seizures, regression in cognitive development, and typically poor prognosis. Dysfunction of KCNQ2 and KCNQ3 channels has emerged as a major cause of neonatal epilepsy. However, our understanding of the cellular mechanisms that may both explain the origins of epilepsy and inform treatment strategies for KCNQ2 and KCNQ3 dysfunction is still lacking. Read More

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SLFN11 inactivation induces proteotoxic stress and sensitizes cancer cells to ubiquitin activating enzyme inhibitor TAK-243.

Cancer Res 2021 Apr 16. Epub 2021 Apr 16.

Center for Cancer Research, Developmental Therapeutics Branch & Laboratory of Molecular Pharmacology, National Cancer Institute

Schlafen11 (SLFN11) inactivation occurs in approximately 50% of cancer cell lines and in a large fraction of patient tumor samples, which leads to chemoresistance. Therefore, new therapeutic approaches are needed to target SLFN11-deficient cancers. To that effect, we conducted a drug screen with the NCATS mechanistic drug library of 1978 compounds in isogenic SLFN11-knockout (KO) and wild-type (WT) leukemia cell lines. Read More

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Probing charge pumping and relaxation of the chiral anomaly in a Dirac semimetal.

Sci Adv 2021 Apr 16;7(16). Epub 2021 Apr 16.

Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD 21218, USA.

The linear band crossings of 3D Dirac and Weyl semimetals are characterized by a charge chirality, the parallel or antiparallel locking of electron spin to its momentum. These materials are believed to exhibit an E · B chiral magnetic effect that is associated with the near conservation of chiral charge. Here, we use magneto-terahertz spectroscopy to study epitaxial CdAs films and extract their conductivities σ(ω) as a function of E · B. Read More

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CD52/GPI- T-Cells Are Enriched for Alloreactive Specificity and Predict Acute Graft-Versus-Host-Disease After Stem Cell Transplantation.

Transplant Cell Ther 2021 Feb 25. Epub 2021 Feb 25.

Institute of Immunology and Immunotherapy, College of Medical and Dental Studies, University of Birmingham and Birmingham Health Partners, Birmingham, United Kingdom; Centre for Clinical Haematology, Queen Elizabeth NHS Foundation Trust and Birmingham Health Partners, Birmingham, United Kingdom.

Alemtuzumab is a CD52-specific lympho-depleting antibody. CD52- T cells emerge under alemtuzumab selection pressure. We sought to investigate the phenotype and function of the CD52- T cell fraction and related their presence to clinical outcome. Read More

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February 2021

Apelin-13 Protects Corpus Cavernosum Against Fibrosis Induced by High-Fat Diet in an MMP-Dependent Mechanism.

J Sex Med 2021 Apr 13. Epub 2021 Apr 13.

Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

Background: An increased fibrosis of the corpora cavernosa is a prevalent process that underlies most cases of erectile dysfunction. Apelin, an endogenous circulating peptide, has been documented as an important effector on cardiovascular homeostasis, controlling vascular function and reducing fibrosis in multiple pathological conditions. Recently, initial studies have shown that Apelin, acting through the APJ receptor, also modulates penile erection, however, the role of this system on penile structure and intracorporal collagen remodeling has not been investigated yet. Read More

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