Extraction of a stromal metastatic gene signature in breast cancer via spatial profiling.

Background: The identification of molecular features characterizing metastatic disease is a critical area of oncology research, as metastatic foci often exhibit distinct biological behaviors compared to primary tumors. While the focus has largely been on the neoplastic cells themselves, the characterization of the associated stroma remains largely underexplored, with significant implications for understanding metastasis.

Main Body: By employing spatially resolved transcriptomics, we analyzed the transcriptional features of primary breast adenocarcinoma and its associated metastatic foci, on a representative set of microregions.

Genetic tracing and topography of spontaneous and stimulated cardiac regeneration in mice.

Despite recent efforts to stimulate endogenous cardiomyocyte proliferation for cardiac regeneration, the lack of reliable in vivo methods for monitoring cardiomyocyte replication has hindered our understanding of its mechanisms. Thymidine analogs, used to label proliferating cells, are unsuitable for long-term cardiac regeneration studies as their DNA incorporation elicits a damage response, leading to their elimination. Here we present CycleTrack, a genetic strategy based on the transcriptional activation of Cre recombinase from a temporally regulated cyclin B2 promoter segment, for permanent labeling of cardiomyocytes passing through the G2/M phase.

Combating aggressive weeds: Reinforcing herbicide resistance in pigeonpea (Cajanus cajan L.) through genome editing.

Pigeonpea (Cajanus cajan L.) is a drought-tolerant, tropical grain legume, rich in dietary proteins, vitamins, and micronutrients. However, the longstanding problem of weed infestation in the fields is a major constraint that significantly hampers the productivity of pigeonpea.

Chemical targeting of prolyl-tRNA synthetase stalls ovarian development and kills malaria vectors.

Objective: Along with rising resistance to antimalarials, the emergence of insecticide resistance in Anopheles mosquito species also remains a serious concern. Here, we reveal two potent compounds that show larvicidal and endectocidal activity against malaria vectors, Anopheles culicifacies and Anopheles stephensi, respectively.

Methods: We investigated larvicidal activity of two inhibitors against III-instar larvae of Anopheles culicifacies.

Presentation, treatment and long-term outcomes of hepatocellular carcinoma in patients with and without HIV: a comparative observational cohort study.

Background: This study explores the epidemiology, treatment and outcomes of hepatocellular carcinoma (HCC) in a sub-Saharan cohort, comparing patients with and without human immunodeficiency virus (HIV).

Methods: A retrospective cohort study of patients treated for HCC from 1 February 2011 to 29 February 2024 at Groote Schuur Hospital, South Africa was performed.

Results: Of the 501 HCC patients, 75 (15.

Malaria in pregnancy and its potential impact on neurodevelopment in children: a systematic review.

Background: Malaria during pregnancy can have adverse effects on fetal development, but its impact on neurodevelopment remains unclear. Although some studies have explored the consequences of prenatal malaria, gaps persist due to inconsistencies in exposure timing, assessment methods, and study designs.

Methods: This systematic review highlighted the gaps in six studies selected from an initial pool of 2029 articles, offering clearer insights into the neurodevelopmental outcomes of prenatal malaria exposure.

Nutrient stress triggers sugar-mediated carotenoid production in algal-bacterial interactions.

This study examined the impact of co-culturing Chlorella saccharophila (UTEX247) with Exiguobacterium sp. strain AMK1 on carotenoid production under nitrate-depleted conditions and 3% CO₂ supplementation. The co-culture significantly enhanced the productivity of lutein (238.

Anti-miRNA therapeutics for uterine fibroids.

Background: Uterine leiomyomas arise from altered uterine smooth muscle cell proliferation in the myometrium. Available treatments are limited and fraught with major side effects. Here, we leveraged data from a high-throughput screening using human microRNA mimics and selected miR-148a-3p as a therapeutic target.

Nuclear retention of unspliced HIV-1 RNA as a reversible post-transcriptional block in latency.

HIV-1 latency is mainly characterized at transcriptional level, and little is known about post-transcriptional mechanisms and their contribution to reactivation. The viral protein Rev controls the nucleocytoplasmic export of unspliced and singly-spliced RNA that is central to proviral replication-competence and is therefore a prerequisite for efficient viral reactivation during the "shock-and-kill" cure therapy. Here we show that during infection and reactivation, unspliced HIV-1 RNA is a subject to complex and dynamic regulation by the Rev cofactor MATR3 and the MTR4 cofactor of the nuclear exosome.

MicroRNA control of stem cell reconstitution and growth in root regeneration.

Plants display a remarkable regeneration capacity, which allows them to replace damaged or lost cells, tissues and organs, and thus recover from a broad spectrum of injuries. Even lost stem cells can be regenerated from non-stem cells after competence acquisition, highlighting the enormous plasticity of plant cells. However, the molecular mechanisms underlying this process are still poorly understood.

Intracoronary cytoprotective gene therapy in a dog with dilated cardiomyopathy: long term follow up.

In large breed dogs, dilated cardiomyopathy (DCM) is the main cause of congestive heart failure (CHF) and sudden cardiac death. The underlying etiology of DCM is usually not definitively identified; however, in predisposed breeds a hereditary etiology is often suspected. Other etiologies, such as toxins and infections, have also been documented or suspected to cause DCM in dogs.

A Case of Persistent KSHV Viremia in the Context of HIV, SARS-CoV-2, and Other Co-Infections.

Despite the high prevalence of latent Kaposi's sarcoma-associated herpesvirus (KSHV) infections in patients from endemic areas with a high human immunodeficiency virus (HIV) prevalence, KSHV lytic reactivation in the context of other co-infections is not well understood. Lytic KSHV infections can contribute to severe inflammatory symptoms and KSHV-associated pathogenesis. We have previously reported on KSHV reactivation upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure in a non-hospitalised cohort of people living with HIV (PLWH).

Structural and Phylogenetic Analysis on the Proofreading Activity of SARS-CoV-2.

Maintenance of genomic integrity is a fundamental characteristic of viruses, however, RNA-dependent RNA Polymerase (RdRp) lacks exonuclease activity for proofreading. To facilitate genomic proofreading in viruses, an independent exonuclease domain assists RdRp to maintain fidelity during replication. In contrast to high fidelity in DNA viruses, RNA viruses have to evolve into new variants through comparatively delicate mutagenesis activity for genetic diversity.

G-protein coupled receptor kinase-2 regulates the migration of chronic lymphocytic leukaemia cells to sphingosine-1 phosphate in vitro and their trafficking in vivo.

Disease progression and drug resistance in patients with chronic lymphocytic leukaemia (CLL) depend on signals from the tumour microenvironment in lymphoid sites. GRK2 inhibits the egress of normal B cells from lymphoid tissues by inducing the downregulation of the S1P-receptor 1 (S1PR1). In this study we investigated the role of GRK2 in the context of CLL using in vitro and in vivo murine models, and also primary samples from CLL patients.

SUMO2/3 conjugation of TDP-43 protects against aggregation.

Cytosolic aggregation of the RNA binding protein TDP-43 (transactive response DNA-binding protein 43) is a hallmark of amyotrophic lateral sclerosis and frontotemporal dementia. Here, we report that during oxidative stress, TDP-43 becomes SUMO2/3-ylated by the SUMO E3 ligase protein PIAS4 (protein inhibitor of activated STAT 4) and enriches in cytoplasmic stress granules (SGs). Upon pharmacological inhibition of TDP-43 SUMO2/3-ylation or PIAS4 depletion, TDP-43 enrichment in SGs is accompanied by irreversible aggregation.

Evolution of Zika prevalence in a dengue hyperendemic municipality in Southern Mexico after the outbreak of 2015 to 2017.

Objective: Estimate the Zika prevalence in a dengueendemic municipality in Mexico, after the outbreak of 2015 to 2017.

Materials And Methods: Three serosurveys were conducted in Tapachula, Chiapas, in September 2018, March 2019 and November 2019. A commercial ZIKV and DENV anti-NS1 IgG ELISA were used to estimate each prevalence, their performance and adjustment of the cut-off value were compared with an in-house DENVs and ZIKV anti-EDIII IgG ELISA and the microneutralization test.

Translation of genomics into routine cardiological practice: insights from a European Society of Cardiology Cardiovascular Round Table.

Cardiovascular diseases (CVD) remain the leading cause of death globally and there is an urgent need for innovative approaches to treatment. One emerging avenue is genetic therapies, which hold particular promise for diseases with a monogenic basis. Gene silencing techniques using antisense oligonucleotides or ribonucleic acid interference strategies are currently at the forefront of genetic therapies in CVD, with several ribonucleic acid-targeted therapies already approved for the treatment of conditions such as familial hypercholesterolaemia and transthyretin amyloidosis.

Cardiomyocyte SORBS2 expression increases in heart failure and regulates integrin interactions and extracellular matrix composition.

Aims: In this study, we aimed to uncover genes associated with stressed cardiomyocytes by combining single-cell transcriptomic datasets from failing cardiac tissue from both humans and mice.

Methods And Results: Our bioinformatic analysis identified SORBS2 as conserved NPPA correlated gene. Using mouse models and cardiac tissue from human heart failure patients, we demonstrated that SORBS2 expression is consistently increased during pathological remodeling, correlates to disease severity and is regulated by GATA4.

Sustainable lipid production by oleaginous yeasts: Current outlook and challenges.

Yeast lipid has gained prominence as a sustainable energy source and so various oleaginous yeasts are being investigated to create efficient lipogenic platforms. This review aims to assess the various biotechnological strategies for enhanced production of yeast lipids via agro-waste processing and media engineering including multiomic analyses, genetic engineering, random mutagenesis, and laboratory adaptive evolution. The review also emphasizes the role of cutting-edge omics technologies in pinpointing differentially expressed genes and enriched networks crucial for designing advanced metabolic engineering strategies for prominent oleaginous yeast species.

Unlocking the potential of blood-stage vaccines for malaria elimination.

Malaria vaccines are crucial for advancing public health and achieving malaria elimination. Currently, pre-erythrocytic vaccines like RTS, S/AS01 and R21/Matrix-M are in use, but their effectiveness is limited. Ongoing research on blood-stage vaccine candidates such as RH5, MSP1 and MSP3 has shown promising results.

Rescue of common and rare exon 2 skipping variants of the GAA gene using modified U1 snRNA.

Background: Pompe disease (PD) is an autosomal recessive lysosomal storage disorder caused by the deficient activity of acid alpha glucosidase (GAA) enzyme due to mutations in the GAA gene. As a result, undigested glycogen accumulates within lysosomes causing their dysfunction. From a clinical point of view, the disease can be classified in infantile-onset (IO) and late-onset (LO) forms.

4,6-Disubstituted pyrimidine-based microtubule affinity-regulating kinase 4 (MARK4) inhibitors: synthesis, characterization, activity and studies.

Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder that significantly impacts the cognitive function and memory of a person. Despite the significant research efforts, the ability to completely prevent or effectively treat AD and its related dementias remains limited. Protein kinases are integral to AD pathology and represent promising targets for therapeutic intervention.

Current insights into molecular mechanisms of environmental stress tolerance in Cyanobacteria.

The photoautotrophic nature of cyanobacteria, coupled with their fast growth and relative ease of genetic manipulation, makes these microorganisms very promising factories for the sustainable production of bio-products from atmospheric carbon dioxide. However, both in nature and in cultivation, cyanobacteria go through different abiotic stresses such as high light (HL) stress, heavy metal stress, nutrient limitation, heat stress, salt stress, oxidative stress, and alcohol stress. In recent years, significant improvement has been made in identifying the stress-responsive genes and the linked pathways in cyanobacteria and developing genome editing tools for their manipulation.

Pharmacological Properties of Extracts-A Plant Used to Treat and Manage Elephantiasis.

(Thunb.) Less. has recently become a plant species of interest to researchers due to its biological activities and less toxic effects.

Thy1-YFP: an effective tool for single cell tracing from neuronal progenitors to mature functionally active neurons.

The differentiation of mouse neurons is a complex process involving cell maturation and branching, occurring during both, embryonic development and differentiation in vitro. To study mouse neuronal morphology, we used the Thy1 YFP-16 mouse strain. Although this mouse strain was described over twenty years ago, detailed studies on projections outgrowth and morphology of neurons are still lacking.