Differences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction.

The 313-variant polygenic risk score (PRS) provides a promising tool for breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed. Here, we explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 225,105 female participants from the UK Biobank.

NOTCH localizes to mitochondria through the TBC1D15-FIS1 interaction and is stabilized via blockade of E3 ligase and CDK8 recruitment to reprogram tumor-initiating cells.

The P53-destabilizing TBC1D15-NOTCH protein interaction promotes self-renewal of tumor-initiating stem-like cells (TICs); however, the mechanisms governing the regulation of this pathway have not been fully elucidated. Here, we show that TBC1D15 stabilizes NOTCH and c-JUN through blockade of E3 ligase and CDK8 recruitment to phosphodegron sequences. Chromatin immunoprecipitation (ChIP-seq) analysis was performed to determine whether TBC1D15-dependent NOTCH1 binding occurs in TICs or non-TICs.

Clinical Significance of Elevated KSHV Viral Load in HIV-Related Kaposi's Sarcoma Patients in South Africa.

Kaposi's sarcoma (KS) is an AIDS-defining illness caused by Kaposi's sarcoma-associated herpesvirus (KSHV) predominantly in the context of HIV-related immune suppression. We aimed to explore the usefulness of KSHV DNA viral load (VL) measurement in predicting the severity, response to treatment and outcome of KS. We retrospectively assessed a cohort of KS patients ( = 94) receiving treatment at Groote Schuur Hospital, Cape Town, South Africa.

Enhancing healthcare access and malaria management via mobile clinics and phone call services in Nuh district of Haryana, India.

Background Objectives: Malaria remains a complex challenge in India due to its diverse epidemiology, multi-ethnic population, and multiplicity of malaria vectors. While progress has been made in reducing malaria nationally, persistent pockets hinder elimination efforts. These challenges include hidden reservoirs, inadequate healthcare, suboptimal surveillance, non-compliance, and subclinical infections.

A molecular circuit linking the BCR to the NAD biosynthetic enzyme NAMPT is an actionable target in Richter syndrome.

This works defines, to the best of our knowledge, for the first time a molecular circuit connecting nicotinamide mononucleoside phosphoribosyl transferase (NAMPT) activity to the B-cell receptor (BCR) pathway. Using 4 distinct xenograft models derived from patients with Richter syndrome (RS-PDX), we show that BCR cross-linking results in transcriptional activation of the nicotinamide adenine dinucleotide (NAD) biosynthetic enzyme NAMPT, with increased protein expression, in turn, positively affecting global cellular NAD levels and sirtuins activity. NAMPT blockade, by using the novel OT-82 inhibitor in combination with either BTK or PI3K inhibitors (BTKi or PI3Ki), induces rapid and potent apoptotic responses in all 4 models, independently of their mutational profile and the expression of the other NAD biosynthetic enzymes, including nicotinate phosphoribosyltransferase.

Marine cyanobacterial biomass is an efficient feedstock for fungal bioprocesses.

Background: Marine cyanobacteria offer many sustainability advantages, such as the ability to fix atmospheric CO, very fast growth and no dependence on freshwater for culture. Cyanobacterial biomass is a rich source of sugars and proteins, two essential nutrients for culturing any heterotroph. However, no previous study has evaluated their application as a feedstock for fungal bioprocesses.

Impact of individual, combined and sequential stress on photosynthesis machinery in rice (Oryza sativa L).

Abiotic stresses such as heat, drought and submergence are major threats to global food security. Despite simultaneous or sequential occurrence of these stresses being recurrent under field conditions, crop response to such stress combinations is poorly understood. Rice is a staple food crop for the majority of human beings.

MicroRNA Signatures for Pancreatic Cancer and Chronic Pancreatitis: Expression Profiling by NGS.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease due to the lack of early detection. Because chronic pancreatitis (CP) patients are a high-risk group for pancreatic cancer, this study aimed to assess the differential miRNA profile in pancreatic tissue of patients with CP and pancreatic cancer.

Methods: MiRNAs were isolated from formalin-fixed paraffin-embedded pancreatic tissue of 22 PDAC patients, 18 CP patients, and 10 normal pancreatic tissues from autopsy (C) cases and processed for next-generation sequencing.

Repurposing FDA-approved drugs to target malaria through inhibition of dihydrofolate reductase in the folate biosynthesis pathway: A prospective approach.

Dihydrofolate reductase (DHFR) is a ubiquitous enzyme that regulates the biosynthesis of tetrahydrofolate among various species of Plasmodium parasite. It is a validated target of the antifolate drug pyrimethamine (Pyr) in Plasmodium falciparum (Pf), but its clinical efficacy has been hampered due to the emergence of drug resistance. This has made the attempt to screen Food & Drug Administration-approved drugs against wild- and mutant PfDHFR by employing an in-silico pipeline to identify potent candidates.

Calcium signaling positively regulates cellulase translation and secretion in a Clr-2-overexpressing, catabolically derepressed strain of Penicillium funiculosum.

Background: Low-cost cellulase production is vital to sustainable second-generation biorefineries. The catabolically derepressed strain of Penicillium funiculosum NCIM1228 (PfMig1 or ∆Mig1) secretes a superior set of cellulolytic enzymes, that are most suitable for 2G biorefineries. At a 3% (w/w) load, the ∆Mig1 secretome can release > 80% of fermentable sugars from lignocellulose at a 15% (w/v) biomass load, irrespective of the type of biomass and pretreatment.

Tracking alternative versions of the galactose gene network in the genus and their expansion after domestication.

When grows on mixtures of glucose and galactose, galactose utilization is repressed by glucose, and induction of the gene network only occurs when glucose is exhausted. Contrary to reference alleles, alternative alleles support faster growth on galactose, thus enabling distinct galactose utilization strategies maintained by balancing selection. Here, we report on new wild populations of harboring alternative versions and, for the first time, of alternative alleles.

Epigenetic Diversity Underlying Seasonal and Annual Variations in Brown Planthopper (BPH) Populations as Revealed by Methylation- sensitive Restriction Assay.

Background: The brown planthopper (BPH) is a monophagous sap-sucking insect pest of rice that is responsible for massive yield loss. BPH populations, even when genetically homogenous, can display a vast range of phenotypes, and the development of effective pest-management strategies requires a good understanding of what generates this phenotypic variation. One potential source could be epigenetic differences.

Severe disease during both primary and secondary dengue virus infections in pediatric populations.

Dengue is a global epidemic causing over 100 million cases annually. The clinical symptoms range from mild fever to severe hemorrhage and shock, including some fatalities. The current paradigm is that these severe dengue cases occur mostly during secondary infections due to antibody-dependent enhancement after infection with a different dengue virus serotype.

linked with increased ethanol production and liver inflammation contribute to the pathophysiology of NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is an emerging global health problem and a potential risk factor for metabolic diseases. The bidirectional interactions between liver and gut made dysbiotic gut microbiome one of the key risk factors for NAFLD. In this study, we reported an increased abundance of in the gut of obese and NASH patients living in India.

The uncharted territory of host-pathogen interaction in tuberculosis.

() effectively manipulates the host processes to establish the deadly respiratory disease, Tuberculosis (TB). has developed key mechanisms to disrupt the host cell health to combat immune responses and replicate efficaciously. antigens such as ESAT-6, 19kDa lipoprotein, Hip1, and Hsp70 destroy the integrity of cell organelles (Mitochondria, Endoplasmic Reticulum, Nucleus, Phagosomes) or delay innate/adaptive cell responses.

Cardiac endothelial ischemia/reperfusion injury-derived protein damage-associated molecular patterns disrupt the integrity of the endothelial barrier.

Human cardiac microvascular endothelial cells (HCMECs) are sensitive to ischemia and vulnerable to damage during reperfusion. The release of damage-associated molecular patterns (DAMPs) during reperfusion induces additional tissue damage. The current study aimed to identify early protein DAMPs in human cardiac microvascular endothelial cells subjected to ischemia-reperfusion injury (IRI) using a proteomic approach and their effect on endothelial cell injury.

The interplay between autophagy and apoptosis: its implication in lung cancer and therapeutics.

Maintaining cellular homeostasis relies on the interplay between apoptosis and autophagy, and disruption in either of these processes can contribute to the development of cancer. Autophagy can hinder the apoptotic process, and when autophagy is inhibited in such instances, it can enhance the rate of apoptosis. However, evidence suggests that excessive autophagy can also lead to apoptotic cell death.

Reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) by SARS-CoV-2 in non-hospitalised HIV-infected patients.

Background: While acute SARS-CoV-2 infection and associated inflammation resulted in substantial morbidity and mortality during the COVID-19 pandemic, particularly in unvaccinated patients, long-term effects of SARS-CoV-2 exposure for reactivation of latent oncogenic herpesviruses, such as KSHV, is unknown.

Methods: We performed a longitudinal observational cross-sectional study on 407 non-hospitalised adult HIV-infected (CD4 count <350 cells/μL) patients attending antiretroviral therapy services in Gugulethu, South Africa, from October 2020 to April 2023.

Findings: KSHV seroprevalence was 53.

Autologous anti-GD2 CAR T cells efficiently target primary human glioblastoma.

Glioblastoma (GBM) remains a deadly tumor. Treatment with chemo-radiotherapy and corticosteroids is known to impair the functionality of lymphocytes, potentially compromising the development of autologous CAR T cell therapies. We here generated pre-clinical investigations of autologous anti-GD2 CAR T cells tested against 2D and 3D models of GBM primary cells.

Analyses of human vaccine-specific circulating and bone marrow-resident B cell populations reveal benefit of delayed vaccine booster dosing with blood-stage malaria antigens.

We have previously reported primary endpoints of a clinical trial testing two vaccine platforms for the delivery of malaria DBPRII: viral vectors (ChAd63, MVA), and protein/adjuvant (PvDBPII with 50µg Matrix-M™ adjuvant). Delayed boosting was necessitated due to trial halts during the pandemic and provides an opportunity to investigate the impact of dosing regimens. Here, using flow cytometry - including agnostic definition of B cell populations with the clustering tool CITRUS - we report enhanced induction of DBPRII-specific plasma cell and memory B cell responses in protein/adjuvant versus viral vector vaccinees.

An Advanced Bioconjugation Strategy for Covalent Tethering of TGFβ3 with Silk Fibroin Matrices and its Implications in the Chondrogenesis Profile of Human BMSCs and Human Chondrocytes: A Paradigm Shift in Cartilage Tissue Engineering.

The transforming growth factor-β class of cytokines plays a significant role in articular cartilage formation from mesenchymal condensation to chondrogenic differentiation. However, their exogenous addition to the chondrogenic media makes the protocol expensive. It reduces the bioavailability of the cytokine to the cells owing to their burst release.

Identification of synthetic consortia from a set of plant-beneficial bacteria.

The use of microbial inoculants in agriculture as biofertilisers and/or biopesticides is an appealing alternative to replace or reduce the practice of agrochemicals. Plant microbiota studies are revealing the different bacterial groups which are populating plant microbiomes re-energising the plant probiotic bacteria (PPB) translational research sector. Some single-microbial strain bioinoculants have proven valid in agriculture (e.