V834L and L858R Comutation Is Associated With Response to Osimertinib in Non-Small-Cell Lung Cancer.

Up-front osimertinib leads to clinical benefit in EGFR V834L and L858R comutated NSCLC.

A comparison of the effects of two cooking methods on arsenic species and nutrient elements in rice.

Rice is one of the major cereal crops in the world, contributing significantly towards the dietary energy and nutrition of more than half of the world's population. However, rice can also be a significant exposure route for inorganic arsenic (iAs). This risk is even greater if rice is cooked with iAs-contaminated water.

p38/MK2 signaling stimulates host cells autophagy pathways to restrict infection.

Autophagy plays an important role in recognizing and protecting cells from invading intracellular pathogens such as . In this work, we investigated the role of p38/MK2 in modulating the host cell susceptibility to infection. Inhibition of p38 or MK2 led to a significant increase of bacterial counts in infected mouse embryonic fibroblasts (MEFs), as well as in MK2-deficient () cells.

Fungal Community Composition at the Last Remaining Wild Site of Yellow Early Marsh Orchid ( ssp. ).

The yellow early marsh orchid ( ssp. ) is a critically endangered terrestrial orchid in Britain. Previous attempts to translocate symbiotic seedlings to a site near the last remaining wild site demonstrated some success, with a 10% survival rate despite adverse weather conditions over a two-year period.

Disparities in Time to Diagnosis Among Patients With Multiple Myeloma.

Background: Multiple myeloma (MM) is one of the most diagnosed hematologic malignancies in the United States. Despite improvements in therapy, health disparities persist among patients with MM. Here, we aim to determine whether there are disparities in time to diagnosis (TTD) among MM patients with regard to income, race/ethnicity, and gender.

5-Iodotubercidin sensitizes cells to RIPK1-dependent necroptosis by interfering with NFκB signaling.

Receptor-interacting protein kinases (RIPK)-1 and -3 play crucial roles in cell fate decisions and are regulated by multiple checkpoint controls. Previous studies have identified IKK1/2- and p38/MK2-dependent checkpoints that phosphorylate RIPK1 at different residues to inhibit its activation. In this study, we investigated TNF-induced death in MAPK-activated protein kinase 2 (MK2)-deficient cells and found that MK2 deficiency or inactivation predominantly leads to necroptotic cell death, even without caspase inhibition.

Mapping of long stretches of highly conserved sequences in over 6 million SARS-CoV-2 genomes.

We identified 11 conserved stretches in over 6.3 million SARS-CoV-2 genomes including all the major variants of concerns. Each conserved stretch is ≥100 nucleotides in length with ≥99.

Emerging mechanistic insights of selective autophagy in hepatic diseases.

Macroautophagy (hereafter referred to as autophagy), a highly conserved metabolic process, regulates cellular homeostasis by degrading dysfunctional cytosolic constituents and invading pathogens the lysosomal system. In addition, autophagy selectively recycles specific organelles such as damaged mitochondria ( mitophagy), and lipid droplets (LDs; lipophagy) or eliminates specialized intracellular pathogenic microorganisms such as hepatitis B virus (HBV) and coronaviruses ( virophagy). Selective autophagy, particularly mitophagy, plays a key role in the preservation of healthy liver physiology, and its dysfunction is connected to the pathogenesis of a wide variety of liver diseases.

Decoding post-translational modifications of mammalian septins.

Septins are cytoskeletal GTPases that form nonpolar filaments and higher-ordered structures and they take part in a wide range of cellular processes. Septins are conserved from yeast to mammals but absent from higher plants. The number of septin genes vary between organisms and they usually form complex heteropolymeric networks.

Selective Depletion of ZAP-Binding CpG Motifs in HCV Evolution.

Hepatitis C virus (HCV) is a bloodborne pathogen that can cause chronic liver disease and hepatocellular carcinoma. The loss of CpGs from virus genomes allows escape from restriction by the host zinc-finger antiviral protein (ZAP). The evolution of HCV in the human host has not been explored in the context of CpG depletion.

PRMT5-mediated regulatory arginine methylation of RIPK3.

The TNF receptor-interacting protein kinases (RIPK)-1 and 3 are regulators of extrinsic cell death response pathways, where RIPK1 makes the cell survival or death decisions by associating with distinct complexes mediating survival signaling, caspase activation or RIPK3-dependent necroptotic cell death in a context-dependent manner. Using a mass spectrometry-based screen to find new components of the ripoptosome/necrosome, we discovered the protein-arginine methyltransferase (PRMT)-5 as a direct interaction partner of RIPK1. Interestingly, RIPK3 but not RIPK1 was then found to be a target of PRMT5-mediated symmetric arginine dimethylation.

Dengue virus induced autophagy is mediated by HMGB1 and promotes viral propagation.

Dengue virus (DENV) exploits various cellular pathways including autophagy to assure enhanced virus propagation. The mechanisms of DENV mediated control of autophagy pathway are largely unknown. Our investigations have revealed a novel role for high-mobility group box1 protein (HMGB1) in regulation of cellular autophagy process in DENV-2 infected A549 cell line.

Hepatitis B Virus-Encoded HBsAg Contributes to Hepatocarcinogenesis by Inducing the Oncogenic Long Noncoding RNA LINC00665 through the NF-κB Pathway.

Clinical and studies have demonstrated a role for hepatitis B virus (HBV)-encoded HBsAg (hepatitis B surface antigen) in HBV-related hepatocellular carcinoma (HCC); however, the underlying mechanisms remain largely unknown. Here, we investigated the role of HBsAg in regulating long noncoding RNAs (lncRNAs) involved in HCC progression. Our analysis of microarray data sets identified LINC00665 as an HBsAg-regulated lncRNA.

The Slowing Rate of CpG Depletion in SARS-CoV-2 Genomes Is Consistent with Adaptations to the Human Host.

Depletion of CpG dinucleotides in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genomes has been linked to virus evolution, host-switching, virus replication, and innate immune responses. Temporal variations, if any, in the rate of CpG depletion during virus evolution in the host remain poorly understood. Here, we analyzed the CpG content of over 1.

Precision Medicine in Low- and Middle-Income Countries.

Most cancer cases occur in low- and middle-income countries (LMICs). The sophisticated technical and human infrastructure needed for optimal diagnosis, treatment, and monitoring of cancers is difficult enough in affluent countries; it is especially challenging in LMICs. In Western, educated, industrial, rich, democratic countries, there is a growing emphasis on and success with precision medicine, whereby targeted therapy is directed at cancers based on the specific genetic lesions in the cancer.

-Cre-Mediated Genetic Deletion of Reveals a Role of Septins in Macrophage Cytokinesis and -Driven Tumorigenesis.

By crossing -floxed mice with -Cre mice carrying the Cre recombinase inserted in the Lysozyme-M () gene locus we aimed the specific deletion of septin7 in myeloid cells, such as monocytes, macrophages and granulocytes. :Cre mice show no alterations in the myeloid compartment. -deleted macrophages (BMDMs) were isolated and analyzed.

Essential nutrient element profiles in rice types: a risk-benefit assessment including inorganic arsenic.

Rice is consumed by nearly half of the global population and a significant source of energy and nutrients. However, rice consumption can also be a significant pathway of inorganic arsenic (iAs) exposure, thus requiring a risk-benefit assessment. This study assessed nutrient element (NE) densities in fifty-five rice types (white, brown and wild rice) marketed in the UK.

Cdc42-Borg4-Septin7 axis regulates HSC polarity and function.

Aging of hematopoietic stem cells (HSCs) is caused by the elevated activity of the small RhoGTPase Cdc42 and an apolar distribution of proteins. Mechanisms by which Cdc42 activity controls polarity of HSCs are not known. Binder of RhoGTPases proteins (Borgs) are known effector proteins of Cdc42 that are able to regulate the cytoskeletal Septin network.

Measuring lncRNA Expression by Real-Time PCR.

Long noncoding RNAs are defined as transcripts longer than 200 nt with no protein coding potential. Most lncRNAs are expressed in a tissue-specific manner and barring a few, their absolute expression is lower compared to most coding transcripts. Differential expression studies have contributed the most to the functional characterisation of the lncRNAs we know.

Fungal Diversity of Selected Habitat Specific Species (Orchidaceae) in the Central Highlands of Madagascar.

About 90% of species are endemic to the biodiversity hotspot of Madagascar. This terrestrial habitat-specific genus received little study for fungal diversity to support conservation. We evaluated the diversity of culturable fungi of 11 species and soil characteristics from six sites spanning a >40 km radius in and along the region's inselbergs.

Living with arsenic in the environment: An examination of current awareness of farmers in the Bengal basin using hybrid feature selection and machine learning.

High levels of arsenic in drinking water and food materials continue to pose a global health challenge. Over 127 million people alone in Bangladesh (BD) and West Bengal (WB) state of India are exposed to elevated levels of arsenic in drinking water. Despite decades of research and outreach, arsenic awareness in communities continue to be low.