Nature of local disorder in β-NaYF-based, near-infrared upconverting core nanocrystals due to deliberate incorporation of a symmetry perturbing agent.

As nanocrystalline materials exhibit complex disorders, assessment of the local disorder at the nanoscale induced by implanted lattice defects plays a crucial role in understanding the structure-function relationship in these materials. In this report, a comprehensive structural analysis was performed on upconverting nanocrystals (UCNCs) of NaYF/Nd/Yb/Tm, containing varying concentrations of Li to induce deliberate lattice defects. Subsequently, a comprehensive structural analysis of the UCNCs was performed using synchrotron radiation-based high-resolution X-ray diffraction (HRXRD), high-energy total angle scattering coupled with pair distribution function (PDF) analysis, neutron diffraction (ND) and EXAFS probing.

Identification and functional validation of miR-190b-5p and miR-296-3p as novel therapeutic attenuators of liver fibrosis.

Background & Aims: Liver fibrosis and its end-stage form cirrhosis contribute to millions of deaths annually. The lack of robust antifibrotic molecules is in part attributed to the absence of any functional screens to identify molecular regulators using patient-derived primary human hepatic myofibroblasts, which are key drivers of fibrosis.

Methods: Here, to identify robust regulators of fibrosis, we performed functional microRNA screenings in primary human hepatic myofibroblasts followed by in vivo validation in three independent mouse models of fibrosis (toxin, cholestasis and MASH).

Behavior of Microstrain in Nd-Sensitized Near-Infrared Upconverting Core-Shell Nanocrystals for Defect-Induced Tailoring of Luminescence Intensity.

In an attempt to optimize the upconversion luminescence (UCL) output of a Nd-sensitized near-infrared (808 nm) upconverting core-shell (CS) nanocrystal through deliberate incorporation of lattice defects, a comprehensive analysis of microstrain both at the CS interface and within the core layer was performed using integral breadth calculation of high-energy synchrotron X-ray (λ = 0.568551 Å) diffraction. An atomic level interpretation of such microstrain was performed using pair distribution function analysis of the high-energy total scattering.

Erythropoietin restrains the inhibitory potential of interneurons in the mouse hippocampus.

Severe psychiatric illnesses, for instance schizophrenia, and affective diseases or autism spectrum disorders, have been associated with cognitive impairment and perturbed excitatory-inhibitory balance in the brain. Effects in juvenile mice can elucidate how erythropoietin (EPO) might aid in rectifying hippocampal transcriptional networks and synaptic structures of pyramidal lineages, conceivably explaining mitigation of neuropsychiatric diseases. An imminent conundrum is how EPO restores synapses by involving interneurons.

Twisted Intramolecular Charge-Transfer State Addition to Electron-Poor Olefins.

When electron-rich arylpyrrolinium salts are irradiated with ultraviolet light in the presence of Michael acceptors, the pyrrolinyl and aryl fragments add to the activated and polarized double bond in a regioselective manner, forming two C-C bonds and fragmenting the substrate. In this paper, we present a model for this intriguing reaction, supported by spectroscopy and computational analyses, and provide evidence for rectifying previously misassigned structures. We postulate that the photochemical reaction is inefficient because the reaction between the twisted intramolecular charge-transfer state and the olefin competes with fluorescence from this state upon photon absorption.

Plxnd1-mediated mechanosensing of blood flow controls the caliber of the Dorsal Aorta via the transcription factor Klf2.

The cardiovascular system generates and responds to mechanical forces. The heartbeat pumps blood through a network of vascular tubes, which adjust their caliber in response to the hemodynamic environment. However, how endothelial cells in the developing vascular system integrate inputs from circulatory forces into signaling pathways to define vessel caliber is poorly understood.

PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome.

The paraneoplastic Ma antigen (PNMA) proteins are associated with cancer-induced paraneoplastic syndromes that present with an autoimmune response and neurological symptoms. Why PNMA proteins are associated with this severe autoimmune disease is unclear. PNMA genes are predominantly expressed in the central nervous system and are ectopically expressed in some tumors.

Transposable elements may enhance antiviral resistance in HIV-1 elite controllers.

Less than 0.5% of people living with HIV-1 are elite controllers (ECs) - individuals who have a replication-competent viral reservoir in their CD4 T cells but maintain undetectable plasma viremia without the help of antiretroviral therapy. While the EC CD4 T cell transcriptome has been investigated for gene expression signatures associated with disease progression (or, in this case, a lack thereof), the expression and regulatory activity of transposable elements (TEs) in ECs has not been explored.

Ribosomal profiling of human endogenous retroviruses in healthy tissues.

Human endogenous retroviruses (HERVs) are the germline embedded proviral fragments of ancient retroviral infections that make up roughly 8% of the human genome. Our understanding of HERVs in physiology primarily surrounds their non-coding functions, while their protein coding capacity remains virtually uncharacterized. Therefore, we applied the bioinformatic pipeline "hervQuant" to high-resolution ribosomal profiling of healthy tissues to provide a comprehensive overview of translationally active HERVs.

Erythropoietin re-wires cognition-associated transcriptional networks.

Recombinant human erythropoietin (rhEPO) has potent procognitive effects, likely hematopoiesis-independent, but underlying mechanisms and physiological role of brain-expressed EPO remained obscure. Here, we provide transcriptional hippocampal profiling of male mice treated with rhEPO. Based on ~108,000 single nuclei, we unmask multiple pyramidal lineages with their comprehensive molecular signatures.

Staring at the onco-exaptation: the two-faced medley of an ancient retrovirus, HERVH.

Cell senescence suppresses tumors by arresting cells at risk of becoming malignant. However, this process in turn can affect the microenvironment, leading to acquisition of a senescence-associated secretory phenotype (SASP) that renders senescent cells proinflammatory and results in tumor progression. But how is SASP controlled? In this issue of the JCI, Attig and Pape et al.

A new human embryonic cell type associated with activity of young transposable elements allows definition of the inner cell mass.

There remains much that we do not understand about the earliest stages of human development. On a gross level, there is evidence for apoptosis, but the nature of the affected cell types is unknown. Perhaps most importantly, the inner cell mass (ICM), from which the foetus is derived and hence of interest in reproductive health and regenerative medicine, has proven hard to define.

PNMA2 forms non-enveloped virus-like capsids that trigger paraneoplastic neurological syndrome.

The () genes are associated with cancer-induced paraneoplastic syndromes that present with neurological symptoms and autoantibody production. How PNMA proteins trigger a severe autoimmune disease is unclear. genes are predominately expressed in the central nervous system with little known functions but are ectopically expressed in some tumors.

The E3 ubiquitin ligase WWP2 regulates pro-fibrogenic monocyte infiltration and activity in heart fibrosis.

Non-ischemic cardiomyopathy (NICM) can cause left ventricular dysfunction through interstitial fibrosis, which corresponds to the failure of cardiac tissue remodeling. Recent evidence implicates monocytes/macrophages in the etiopathology of cardiac fibrosis, but giving their heterogeneity and the antagonizing roles of macrophage subtypes in fibrosis, targeting these cells has been challenging. Here we focus on WWP2, an E3 ubiquitin ligase that acts as a positive genetic regulator of human and murine cardiac fibrosis, and show that myeloid specific deletion of WWP2 reduces cardiac fibrosis in hypertension-induced NICM.

Photochemical Decarbonylation of Oxetanone and Azetidinone: Spectroscopy, Computational Models, and Synthetic Applications.

Photoexcitation of cyclic ketones leads to the expulsion of carbon monoxide and a mixture of products derived from diradical intermediates. Here we show that synthetic utility of this process is improved if strained heterocyclic ketones are used. Photochemistry of 3-oxetanone and N-Boc-3-azetidinone has not been previously described.

Evolution and antiviral activity of a human protein of retroviral origin.

Endogenous retroviruses are abundant components of mammalian genomes descended from ancient germline infections. In several mammals, the envelope proteins encoded by these elements protect against exogenous viruses, but this activity has not been documented with endogenously expressed envelopes in humans. We report that the human genome harbors a large pool of envelope-derived sequences with the potential to restrict retroviral infection.

A Novel Gene Controls a New Structure: PiggyBac Transposable Element-Derived 1, Unique to Mammals, Controls Mammal-Specific Neuronal Paraspeckles.

Although new genes can arrive from modes other than duplication, few examples are well characterized. Given high expression in some human brain subregions and a putative link to psychological disorders [e.g.

Vitamin B and folate decrease inflammation and fibrosis in NASH by preventing syntaxin 17 homocysteinylation.

Background & Aims: Several recent clinical studies have shown that serum homocysteine (Hcy) levels are positively correlated, while vitamin B (B) and folate levels are negative correlated, with non-alcoholic steatohepatitis (NASH) severity. However, it is not known whether hyperhomocysteinemia (HHcy) plays a pathogenic role in NASH.

Methods: We examined the effects of HHcy on NASH progression, metabolism, and autophagy in dietary and genetic mouse models, patients, and primates.

New Insights into Hippo/YAP Signaling in Fibrotic Diseases.

Fibrosis results from defective wound healing processes often seen after chronic injury and/or inflammation in a range of organs. Progressive fibrotic events may lead to permanent organ damage/failure. The hallmark of fibrosis is the excessive accumulation of extracellular matrix (ECM), mostly produced by pathological myofibroblasts and myofibroblast-like cells.

Rumen multi-omics addressing diet-host-microbiome interplay in farm animals: a review.

Continuous improvement in the living standards of developing countries, calls for an urgent need of high quality meat and dairy products. The farm animals have a micro-ecosystem in gastro-intestinal tract, comprising of a wide variety of flora and fauna which converts roughages and agricultural byproducts as well as nutrient rich concentrate sources into the useful products such as volatile fatty acids and microbial crude proteins. The microbial diversity changes according to composition of the feed, host species/breed and host's individual genetic makeup.

A Single Functionalization Agent for Heterotelechelic ROMP Polymers.

Heterotelechelic polymers are an important class of materials finding applications in bioconjugation, imaging, sensing, and synthesis of organic/inorganic hybrid systems with interesting features. However, the synthesis of such polymers is challenging. Here, we report a mechanistically unique and most efficient method based on a single functionalization agent to prepare heterotelechelic polymers by a ring-opening metathesis polymerization.