johnnySoftData/distilroberta-ai-bio-embeddings
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This study reveals the genetic and physical interactions between the key recombination proteins AtMND1, AtDMC1, AtRAD51, and AtXRCC3 during meiosis in Arabidopsis. | During meiosis, homologous chromosomes recognize each other, align, and exchange genetic information. This process requires the action of RecA-related proteins Rad51 and Dmc1 to catalyze DNA strand exchanges. The Mnd1–Hop2 complex has been shown to assist in Dmc1-dependent processes. Furthermore, higher eukaryotes poss... | Crossovers (COs) are at the origin of genetic variability, occurring across successive generations, and they are also essential for the correct segregation of chromosomes during meiosis. Their number and position are precisely controlled, however the mechanisms underlying these controls are poorly understood. Neddylati... |
IKAP facilitates meiosis during male gametogenesis through its roles in regulating meiotic gene transcription and wobble uridine tRNA modification. | Mouse Ikbkap gene encodes IKAP—one of the core subunits of Elongator—and is thought to be involved in transcription. However, the biological function of IKAP, particularly within the context of an animal model, remains poorly characterized. We used a loss-of-function approach in mice to demonstrate that Ikbkap is essen... | Improper gene regulation is implicated in reproductive isolation, but its genetic and molecular bases are unknown. We previously reported that a mouse inter-subspecific X chromosome substitution strain shows reproductive isolation characterized by male-specific sterility due to disruption of meiotic entry in spermatoge... |
Bclaf1 is essential for type I interferon signaling as it promotes STAT1/STAT2 phosphorylation and facilitates ISGF3 binding to IFN-stimulated response elements. | Type I interferon response plays a prominent role against viral infection, which is frequently disrupted by viruses. Here, we report Bcl-2 associated transcription factor 1 (Bclaf1) is degraded during the alphaherpesvirus Pseudorabies virus (PRV) and Herpes simplex virus type 1 (HSV-1) infections through the viral prot... | Human herpesvirus 8 (HHV-8) encodes four viral interferon regulatory factors (vIRFs) that target cellular IRFs and/or other innate-immune and stress signaling regulators and suppress the cellular response to viral infection and replication. For vIRF-1, cellular protein targets include IRFs, p53, p53-activating ATM kina... |
Socioeconomic vulnerabilities such as poverty, debt, and dowry obligations compel individuals to sell their kidneys, sometimes leading former victims to become brokers themselves. | Globally, demands for the kidneys have surpassed supply both living and deceased donors. High demands relative to the availability have made the kidney one of the most saleable human organs. The main objective was to explore the drivers of kidney selling. Literature related to kidney selling and its drivers was explore... | About 295,000 women died globally during and following pregnancy and childbirth in 2017. Two-thirds of these deaths occurred in Sub-Saharan Africa. By linking individual and regional data from 135 regions in 17 Sub-Saharan African countries over the period 2002–2018 this study explores how bribery affects maternal mort... |
Researchers used mouse genome data to demonstrate that widespread adaptive evolution occurs in both coding and noncoding regions, with background selection explaining diversity reductions around noncoding elements but not exons. | The contribution of regulatory versus protein change to adaptive evolution has long been controversial. In principle, the rate and strength of adaptation within functional genetic elements can be quantified on the basis of an excess of nucleotide substitutions between species compared to the neutral expectation or from... | The relative contributions of neutral and adaptive substitutions to molecular evolution has been one of the most controversial issues in evolutionary biology for more than 40 years. The analysis of within-species nucleotide polymorphism and between-species divergence data supports a widespread role for adaptive protein... |
During intracellular replication, Toxoplasma gondii shares plasma membranes that undergo Rab5b and MyoF-dependent endo-exocytic cycling. | During intracellular development, apicomplexan parasites reside within a parasitophorous vacuole largely derived from the host plasma membrane (PM) and rendered nonfusogenic with the host endolysosomal system. Yet, the parasite is capable of protein uptake from the host cell via endocytosis, which occurs via a conserve... | Malaria parasite release (egress) from host red blood cells involves parasite-mediated membrane poration and rupture, thought to involve membrane-lytic effector molecules such as perforin-like proteins and/or phospholipases. With the aim of identifying these effectors, we disrupted the expression of two Plasmodium falc... |
Nef protects SIV-infected sooty mangabeys from CD4+ T cell loss by downmodulating TCR-CD3 to prevent activation-induced cell death and MHC-I to reduce immune cell lysis. | Recent data suggest that Nef-mediated downmodulation of TCR-CD3 may protect SIVsmm-infected sooty mangabeys (SMs) against the loss of CD4+ T cells. However, the mechanisms underlying this protective effect remain unclear. To further assess the role of Nef in nonpathogenic SIV infection, we cloned nef alleles from 11 SI... | Understanding the mechanism of infection control in elite controllers (EC) may shed light on the correlates of control of disease progression in HIV infection. However, limitations have prevented a clear understanding of the mechanisms of elite controlled infection, as these studies can only be performed at randomly se... |
Following the 2013 emergence of Chikungunya virus in the Americas, scientists studied infected individuals to track the virus's genetic changes. | Background Chikungunya virus (CHIKV), an alphavirus and member of the Togaviridae family, is capable of causing severe febrile disease in humans. In December of 2013 the Asian Lineage of CHIKV spread from the Old World to the Americas, spreading rapidly throughout the New World. Given this new emergence in naïve popula... | Background Chikungunya virus (CHIKV) is an emerging mosquito-borne pathogen circulating in tropical and sub-tropical regions. Although autochthonous transmission has not been reported in Australia, there is a potential risk of local CHIKV outbreaks due to the presence of suitable vectors, global trade, frequent interna... |
Disease and injury rates exhibit significant regional variations within middle-income countries like Mexico. | Background Rates of diseases and injuries and the effects of their risk factors can have substantial subnational heterogeneity, especially in middle-income countries like Mexico. Subnational analysis of the burden of diseases, injuries, and risk factors can improve characterization of the epidemiological transition and... | This study aims to assess the progress of geographic, socioeconomic, and demographic disparities in Covid-19 vaccination coverage in Brazil over the first two years of the vaccination campaign. Data from the National Immunization Program Information System were used to estimate covid-19 vaccine coverage. Brazilian muni... |
The lncRNA NKILA plays a crucial tumor-suppressive role in the pathogenesis of nasopharyngeal carcinoma, a disease heavily influenced by local inflammation. | The role of long non-coding RNA (lncRNA) in the progression of Nasopharyngeal carcinoma (NPC) has not been fully elucidated. The study was designed to explore the functional role of NKILA, a newly identified lncRNA, in the progression of NPC. We performed a lncRNA expression profile microarray using four NPC and paired... | Oesophageal adenocarcinoma (OAC) is one of the ten most prevalent forms of cancer and is showing a rapid increase in incidence and yet exhibits poor survival rates. Compared to many other common cancers, the molecular changes that occur in this disease are relatively poorly understood. However, genes encoding chromatin... |
Plasmacytoid dendritic cells primarily recognize HIV-infected lymphocytes through the endosomal TLR7 pathway. | Cell-free HIV-1 virions are poor stimulators of type I interferon (IFN) production. We examined here how HIV-infected cells are recognized by plasmacytoid dendritic cells (pDCs) and by other cells. We show that infected lymphocytes are more potent inducers of IFN than virions. There are target cell-type differences in ... | Type III interferons (IFN-lambdas(λ)) are important cytokines that inhibit viruses and modulate immune responses by acting through a unique IFN-λR1/IL-10RB heterodimeric receptor. Until now, the primary antiviral function of IFN-λs has been proposed to be at anatomical barrier sites. Here, we examine the regulation of ... |
The prevalence of childhood anemia in the study area was found to decrease as children age and as household wealth improves. | Childhood anemia affects around half of under five children and has impacts on physical, mental, and social development, both in the short and long term. The objective of the study was to determine the prevalence of anemia and its associated factors among under-five children living in Arba Minch Health and Demographic ... | Micronutrient deficiencies can hurt the health of women of reproductive age (WRA), their pregnancy outcomes, and the growth and development of their offspring in sub-Saharan African countries. The present study aimed to estimate the dietary intake of non-pregnant and non-lactating (NPNL) WRA, residing in seven district... |
Researchers introduce a biologically plausible neural architecture that integrates amortized and iterative inference to balance speed and accuracy. | Predictive coding is an influential model of cortical neural activity. It proposes that perceptual beliefs are furnished by sequentially minimising “prediction errors”—the differences between predicted and observed data. Implicit in this proposal is the idea that successful perception requires multiple cycles of neural... | The principles by which networks of neurons compute, and how spike-timing dependent plasticity (STDP) of synaptic weights generates and maintains their computational function, are unknown. Preceding work has shown that soft winner-take-all (WTA) circuits, where pyramidal neurons inhibit each other via interneurons, are... |
Escherichia coli rapidly adapts to the mouse intestine through single point mutations in the EnvZ/OmpR regulatory system. | While pleiotropic adaptive mutations are thought to be central for evolution, little is known on the downstream molecular effects allowing adaptation to complex ecologically relevant environments. Here we show that Escherichia coli MG1655 adapts rapidly to the intestine of germ-free mice by single point mutations in En... | Escherichia coli is a commensal of the intestine of most mammals, but also an important human pathogen. Within a healthy human its population structure is highly dynamic, where typically a dominant E. coli strain is accompanied by several low abundance satellite strains. However, the factors underlying E. coli strain d... |
KSHV uses the lytic protein ORF57 to inhibit stress granule formation and evade the host antiviral response. | TIA-1 positive stress granules (SG) represent the storage sites of stalled mRNAs and are often associated with the cellular antiviral response. In this report, we provide evidence that Kaposi’s sarcoma-associated herpesvirus (KSHV) overcomes the host antiviral response by inhibition of SG formation via a viral lytic pr... | Kaposi’s sarcoma-associated herpesvirus (KSHV) is causally associated with Kaposi’s sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman’s disease. The IFIT family of proteins inhibits replication of some viruses, but their effects on KSHV lytic replication was unknown. Here we show that KSHV lytic repli... |
The carbomer-based adjuvant Adjuplex safely stimulates robust CD8 T-cell immunity to protect against intracellular pathogens. | There is a critical need for adjuvants that can safely elicit potent and durable T cell-based immunity to intracellular pathogens. Here, we report that parenteral vaccination with a carbomer-based adjuvant, Adjuplex (ADJ), stimulated robust CD8 T-cell responses to subunit antigens and afforded effective immunity agains... | Severe Acute Respiratory Syndrome caused substantial morbidity and mortality during the 2002–2003 epidemic. Many of the features of the human disease are duplicated in BALB/c mice infected with a mouse-adapted version of the virus (MA15), which develop respiratory disease with high morbidity and mortality. Here, we sho... |
Integrating Sickle Cell Disease screening and care into existing primary healthcare services could significantly reduce childhood mortality in Cameroon despite limited resources. | Sickle Cell Disease (SCD) is a serious genetic disorder with astounding regional differences in childhood survival. Alarmingly, over 90% of children with SCD in SSA die before their fifth birthday. In Cameroon, approximately 7,000 children are born with SCD annually; however, most of them go undiagnosed until their fou... | The World Health Organization (WHO) model list of Essential In vitro Diagnostic (EDL) introduced in 2018 complements the established Essential Medicines List (EML) and improves its impact on advancing universal health coverage and better health outcomes. We conducted a scoping review of the literature on implementing t... |
To prevent widespread treatment failure, a faster and more accessible genotyping assay is urgently needed to track benzimidazole resistance in tropical parasitic infections. | Background Soil-transmitted helminths (STHs) are the most prevalent intestinal helminths of humans, and a major cause of morbidity in tropical and subtropical countries. The benzimidazole (BZ) drugs albendazole (ABZ) and mebendazole (MBZ) are used for treatment of human STH infections and this use is increasing dramati... | Global efforts to address schistosomiasis and soil-transmitted helminthiases (STH) include deworming programs for school-aged children that are made possible by large-scale drug donations. Decisions on these mass drug administration (MDA) programs currently rely on microscopic examination of clinical specimens to deter... |
Individuals lacking a trusted information source or doubting vaccine safety and efficacy, as well as women, were significantly more likely to exhibit COVID-19 vaccine hesitancy. | There is very limited data on the extent and determinants of COVID-19 vaccine hesitancy among adults living in sub-Saharan Africa since the global roll-out of vaccines began in 2021. This multi-country survey sought to investigate COVID-19 vaccine hesitancy and other predictors of readiness to get vaccinated. We conduc... | Handwashing is essential for respiratory virus prevention, but uptake of handwashing in the context of the SARS-CoV-2 pandemic remains under-explored. This study examines trends in and determinants of handwashing practices for COVID-19 prevention in 10 countries in West, East, and Southern Africa. Data are derived from... |
Ablation of the BAHD1 gene in mice leads to severe metabolic deficiencies, placental growth restriction, and high neonatal mortality. | BAHD1 is a vertebrate protein that promotes heterochromatin formation and gene repression in association with several epigenetic regulators. However, its physiological roles remain unknown. Here, we demonstrate that ablation of the Bahd1 gene results in hypocholesterolemia, hypoglycemia and decreased body fat in mice. ... | Endometriosis is a gynecological disease defined by the extrauterine growth of endometrial-like cells that cause chronic pain and infertility. The disease is limited to primates that exhibit spontaneous decidualization, and diseased cells are characterized by significant defects in the steroid-dependent genetic pathway... |
Researchers used single-cell FRET to show that only ESX-1 competent strains of M. tuberculosis and M. marinum can cause phagolysosomal rupture and subsequent host cell necrosis. | Survival within macrophages is a central feature of Mycobacterium tuberculosis pathogenesis. Despite significant advances in identifying new immunological parameters associated with mycobacterial disease, some basic questions on the intracellular fate of the causative agent of human tuberculosis in antigen-presenting c... | In a study of household contacts (HHC), households were categorized into High (HT) and Low (LT) transmission groups based on the proportion of HHC with a positive tuberculin skin test. The Mycobacterium tuberculosis (Mtb) strains from HT and LT index cases of the households were designated Mtb-HT and Mtb-LT, respective... |
An evidence gap map of 133 studies synthesizes the global impact of climate change on maternal health and highlights critical areas requiring further investigation. | Climate change poses unique challenges to maternal well-being and increases complications during pregnancy and childbirth globally. This evidence gap map (EGM) aims to identify gaps in existing knowledge and areas where further research related to climate change and its impact on maternal health is required. The follow... | Fear of infection and measures taken to mitigate infection, such as social distancing, lockdown and isolation can lead to anxiety and depression across the life course, but especially in pregnancy. We set out to identify the prevalence of depression in pregnancy, using Edinburgh Postnatal Depression Scale (EPDS) during... |
Researchers developed an infection assay revealing that various clade 2 and 3 sarbecoviruses utilize human and bat ACE2 proteins for cell entry. | Viral spillover from animal reservoirs can trigger public health crises and cripple the world economy. Knowing which viruses are primed for zoonotic transmission can focus surveillance efforts and mitigation strategies for future pandemics. Successful engagement of receptor protein orthologs is necessary during cross-s... | Background In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) was identified as the etiological agent of severe acute respiratory syndrome, a disease characterized by severe pneumonia that sometimes results in death. SARS-CoV is a zoonotic virus that crossed the species barrier, most likely originating f... |
Uncovering the poorly understood allosteric mechanism of STAT3 provides new insights for the pharmaceutical control of its cancer-related activity. | Signal Transducer and Activator of Transcription 3 (STAT3) plays a crucial role in cancer development and thus is a viable target for cancer treatment. STAT3 functions as a dimer mediated by phosphorylation of the SRC-homology 2 (SH2) domain, a key target for therapeutic drugs. While great efforts have been employed to... | The Src family of tyrosine kinases (SFKs) regulate numerous aspects of cell growth and differentiation and are under the principal control of the C-terminal Src Kinase (Csk). Csk and SFKs share a modular design with the kinase domain downstream of the N-terminal SH2 and SH3 domains that regulate catalytic function and ... |
Specific class I peptide recognition motifs in HLA-A and HLA-B genes confer significant genetic resistance or susceptibility to Nasopharyngeal carcinoma in the Chinese population. | Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study... | The major histocompatibility complex (MHC) is recognised as one of the most important genetic regions in relation to common human disease. Advancement in identification of MHC genes that confer susceptibility to disease requires greater knowledge of sequence variation across the complex. Highly duplicated and polymorph... |
A biophysical model of epithelial migration demonstrates that wound healing is fundamentally a mechanical process that cell signaling merely modifies. | When a gash or gouge is made in a confluent layer of epithelial cells, the cells move to fill in the “wound.” In some cases, such as in wounded embryonic chick wing buds, the movement of the cells is driven by cortical actin contraction (i.e., a purse string mechanism). In adult tissue, though, cells apparently crawl t... | Cellular senescence is known to drive age-related pathology through the senescence-associated secretory phenotype (SASP). However, it also plays important physiological roles such as cancer suppression, embryogenesis and wound healing. Wound healing is a tightly regulated process which when disrupted results in conditi... |
The Drosophila transcription factor Apterous regulates both the consolidation and maintenance of long-term memory through distinct mechanisms in different neuronal populations. | Memory is initially labile but can be consolidated into stable long-term memory (LTM) that is stored in the brain for extended periods. Despite recent progress, the molecular and cellular mechanisms underlying the intriguing neurobiological processes of LTM remain incompletely understood. Using the Drosophila courtship... | Adaptive decision-making depends on the formation of novel memories. In Drosophila, the mushroom body (MB) is the site of associative olfactory long-term memory (LTM) storage. However, due to the sparse and stochastic representation of olfactory information in Kenyon cells (KCs), genetic access to individual LTMs remai... |
Caspase-1 drives macrophage pyroptosis and the release of IL-18, which protects the host by inducing IFNγ-dependent reactive oxygen species. | Infection with Burkholderia pseudomallei or B. thailandensis triggers activation of the NLRP3 and NLRC4 inflammasomes leading to release of IL-1β and IL-18 and death of infected macrophages by pyroptosis, respectively. The non-canonical inflammasome composed of caspase-11 is also activated by these bacteria and provide... | Pulmonary Francisella tularensis and Burkholderia pseudomallei infections are highly lethal in untreated patients, and current antibiotic regimens are not always effective. Activating the innate immune system provides an alternative means of treating infection and can also complement antibiotic therapies. Several natur... |
Mutations in the Arabidopsis axr1 gene disrupt the neddylation pathway, causing meiotic crossovers to mislocalize and cluster together. | Crossovers (COs) are at the origin of genetic variability, occurring across successive generations, and they are also essential for the correct segregation of chromosomes during meiosis. Their number and position are precisely controlled, however the mechanisms underlying these controls are poorly understood. Neddylati... | During meiosis, homologous chromosomes recognize each other, align, and exchange genetic information. This process requires the action of RecA-related proteins Rad51 and Dmc1 to catalyze DNA strand exchanges. The Mnd1–Hop2 complex has been shown to assist in Dmc1-dependent processes. Furthermore, higher eukaryotes poss... |
Different RHDV strains exhibit strain-specific binding preferences for A, B, and H type 2 HBGA epitopes, targeting distinct rabbit subgroups. | Rabbit Hemorrhagic disease virus (RHDV), a calicivirus of the Lagovirus genus, and responsible for rabbit hemorrhagic disease (RHD), kills rabbits between 48 to 72 hours post infection with mortality rates as high as 50–90%. Caliciviruses, including noroviruses and RHDV, have been shown to bind histo-blood group antige... | All viruses need to bind to specific receptor molecules on the surface of target cells to initiate infection. Virus–receptor binding is highly specific, and this specificity determines both the species and the cell type that can be infected by a given virus. In some well-studied cases, the virus-binding region on the r... |
The framework reveals that genes crucial to the central nervous system and autism spectrum disorders are intolerant to both missense and loss-of-function mutations. | A challenge in medical genomics is to identify variants and genes associated with severe genetic disorders. Based on the premise that severe, early-onset disorders often result in a reduction of evolutionary fitness, several statistical methods have been developed to predict pathogenic variants or constrained genes bas... | Predicting the effects of mutations on protein function is an important issue in evolutionary biology and biomedical applications. Computational approaches, ranging from graphical models to deep-learning architectures, can capture the statistical properties of sequence data and predict the outcome of high-throughput mu... |
A computational theory-of-mind model classifies subjects' depth-of-thought during an economic exchange game. | Reciprocating exchange with other humans requires individuals to infer the intentions of their partners. Despite the importance of this ability in healthy cognition and its impact in disease, the dimensions employed and computations involved in such inferences are not clear. We used a computational theory-of-mind model... | Psychiatric disorders are ubiquitously characterized by debilitating social impairments. These difficulties are thought to emerge from aberrant social inference. In order to elucidate the underlying computational mechanisms, patients diagnosed with major depressive disorder (N = 29), schizophrenia (N = 31), and borderl... |
Researchers demonstrate that the AtMND1-AHP2 complex directly interacts with AtRAD51 and AtDMC1 to mediate meiotic recombination. | During meiosis, homologous chromosomes recognize each other, align, and exchange genetic information. This process requires the action of RecA-related proteins Rad51 and Dmc1 to catalyze DNA strand exchanges. The Mnd1–Hop2 complex has been shown to assist in Dmc1-dependent processes. Furthermore, higher eukaryotes poss... | Crossovers (COs) are at the origin of genetic variability, occurring across successive generations, and they are also essential for the correct segregation of chromosomes during meiosis. Their number and position are precisely controlled, however the mechanisms underlying these controls are poorly understood. Neddylati... |
By integrating variant-level features and gene-level selective constraints, UNEECON outperforms existing methods in prioritizing genes and variants linked to autosomal dominant disorders. | A challenge in medical genomics is to identify variants and genes associated with severe genetic disorders. Based on the premise that severe, early-onset disorders often result in a reduction of evolutionary fitness, several statistical methods have been developed to predict pathogenic variants or constrained genes bas... | Predicting the effects of mutations on protein function is an important issue in evolutionary biology and biomedical applications. Computational approaches, ranging from graphical models to deep-learning architectures, can capture the statistical properties of sequence data and predict the outcome of high-throughput mu... |
Successive vaccinations could potentially enhance the immune response by manipulating the natural mutation and selection process of B cells to produce higher-affinity antibodies. | Antibodies stand between us and pathogens. Viruses mutate quickly to avoid detection, and antibodies mutate at similar rates to hunt them down. This death spiral is fueled by specialized proteins and error-prone polymerases that change DNA sequences. Here, we explore how B lymphocytes stay in the race by expressing act... | VDJ rearrangement and somatic hypermutation work together to produce antibody-coding B cell receptor (BCR) sequences for a remarkable diversity of antigens. It is now possible to sequence these BCRs in high throughput; analysis of these sequences is bringing new insight into how antibodies develop, in particular for br... |
Global regulatory systems allow bacteria to simultaneously fine-tune multiple physiological activities when adapting to complex environments. | While pleiotropic adaptive mutations are thought to be central for evolution, little is known on the downstream molecular effects allowing adaptation to complex ecologically relevant environments. Here we show that Escherichia coli MG1655 adapts rapidly to the intestine of germ-free mice by single point mutations in En... | Escherichia coli is a commensal of the intestine of most mammals, but also an important human pathogen. Within a healthy human its population structure is highly dynamic, where typically a dominant E. coli strain is accompanied by several low abundance satellite strains. However, the factors underlying E. coli strain d... |
Neurons exhibit high variability in ion channel conductances due to changes in their intrinsic input/output functions over a lifetime. | Every neuron is part of a network, exerting its function by transforming multiple spatiotemporal synaptic input patterns into a single spiking output. This function is specified by the particular shape and passive electrical properties of the neuronal membrane, and the composition and spatial distribution of ion channe... | The activity of trans-membrane proteins such as ion channels is the essence of neuronal transmission. The currently most accurate method for determining ion channel kinetic mechanisms is single-channel recording and analysis. Yet, the limitations and complexities in interpreting single-channel recordings discourage man... |
HIV-1 neutralizing antibodies PGT151 and PGT145 target distinct viral populations, resulting in different persistent fractions of infectivity. | Neutralizing antibodies (NAbs) to multiple epitopes on the HIV-1-envelope glycoprotein (Env) have been isolated from infected persons. The potency of NAbs is measured more often than the size of the persistent fraction of infectivity at maximum neutralization, which may also influence preventive efficacy of active or p... | Eliciting broadly neutralizing antibodies (bnAbs) targeting envelope (Env) is a major goal of HIV vaccine development, but cross-clade breadth from immunization has only sporadically been observed. Recently, Xu et al (2018) elicited cross-reactive neutralizing antibody responses in a variety of animal models using immu... |
Single pyramidal neurons can thus induce targeted inhibitory plasticity to effectively alter the computation of temporally coded information in the cortex. | In the neocortex, the coexistence of temporally locked excitation and inhibition governs complex network activity underlying cognitive functions, and is believed to be altered in several brain diseases. Here we show that this equilibrium can be unlocked by increased activity of layer 5 pyramidal neurons of the mouse ne... | In the human neocortex, single excitatory pyramidal cells can elicit very large glutamatergic EPSPs (VLEs) in inhibitory GABAergic interneurons capable of triggering their firing with short (3–5 ms) delay. Similar strong excitatory connections between two individual neurons have not been found in nonhuman cortices, sug... |
A complementary framework and impact classification system are proposed to improve the management of marine non-indigenous species. | Assessment of the ecological and economic/societal impacts of the introduction of non-indigenous species (NIS) is one of the primary focus areas of bioinvasion science in terrestrial and aquatic environments, and is considered essential to management. A classification system of NIS, based on the magnitude of their envi... | The significance of symbioses between eukaryotic hosts and microbes extends from the organismal to the ecosystem level and underpins the health of Earth’s most threatened marine ecosystems. Despite rapid growth in research on host-associated microbes, from individual microbial symbionts to host-associated consortia of ... |
Novel anti-Leishmanial compounds were developed by improving the metabolic stability of a library hit, but two promising in vitro candidates failed to show in vivo efficacy due to poor drug exposure. | Leishmaniasis is a major infectious disease with hundreds of thousands of new cases and over 20,000 deaths each year. The current drugs to treat this life-threatening infection have several drawbacks such as toxicity and long treatment regimens. A library of 1.8 million compounds, from which the hits reported here are ... | Background Mucosal or mucocutaneous leishmaniasis is the most severe form of tegumentary leishmaniasis due to its destructive character and potential damage to respiratory and digestive tracts. The current treatment recommendations are based on low or very low-quality evidence, and pentavalent antimonial derivatives re... |
The critical gap between diagnostic testing and patient care in tropical Africa is worsened by rare molecular labs and poorly understood bacterial pathogens. | Background In tropical Africa, where the spectrum of the bacterial pathogens that cause fevers is poorly understood and molecular-based diagnostic laboratories are rare, the time lag between test results and patient care is a critical point for treatment of disease. | Antimicrobial resistant pathogens are a leading cause of morbidity and mortality worldwide, with overuse and misuse of antimicrobials being key contributors. We aimed to identify factors associated with antibiotic prescriptions among patients presenting to clinics in Kenya. We performed a retrospective, descriptive coh... |
This Ethiopian study seeks to explain the lack of reported human and animal cases of priority zoonotic diseases within pastoralist populations. | Background Anthrax and brucellosis are endemic national priority zoonotic diseases in Ethiopia. This study assess the possible factors explaining the current limited information available on animal and human cases in pastoral communities. | Introduction Zoonotic disease (ZD) pose a serious threat to human health in low-income countries. In these countries the human burden of disease is often underestimated due to insufficient monitoring because of insufficient funding. Quantification of the impact of zoonoses helps in prioritizing healthcare needs. Kyrgyz... |
By blocking DSP1, Xenorhabdus hominickii metabolites shut down the Toll-PLA2 signaling cascade and induce severe insect immunosuppression. | Xenorhabdus hominickii, an entomopathogenic bacterium, inhibits eicosanoid biosynthesis of target insects to suppress their immune responses by inhibiting phospholipase A2 (PLA2) through binding to a damage-associated molecular pattern (DAMP) molecule called dorsal switch protein 1 (DSP1) from Spodoptera exigua, a lepi... | Immune response against infections can be divided into mechanisms of resistance that ensure active pathogen elimination, and mechanisms of disease tolerance, which include processes that return the host to physiological homeostasis without direct control of pathogen load. Studies on host immune response to infection ha... |
The parasitic success of asexual root-knot nematodes is explained by composite, hybrid-origin genomes that promote gene expression plasticity without meiosis. | Root-knot nematodes (genus Meloidogyne) exhibit a diversity of reproductive modes ranging from obligatory sexual to fully asexual reproduction. Intriguingly, the most widespread and devastating species to global agriculture are those that reproduce asexually, without meiosis. To disentangle this surprising parasitic su... | Background A better understanding of reproductive processes in parasitic nematodes may lead to development of new anthelmintics and control strategies for combating disabling and disfiguring neglected tropical diseases such as lymphatic filariasis and onchocerciasis. Transcriptomatic analysis has provided important new... |
The conserved C isoform of SYD-1 mediates combinatorial signaling between UNC-40 and SAX-3 to integrate directional guidance cues. | During development, axons must integrate directional information encoded by multiple guidance cues and their receptors. Axon guidance receptors, such as UNC-40 (DCC) and SAX-3 (Robo), can function individually or combinatorially with other guidance receptors to regulate downstream effectors. However, little is known ab... | The construction of a large dendritic arbor requires robust growth and the precise delivery of membrane and protein cargoes to specific subcellular regions of the developing dendrite. How the microtubule-based vesicular trafficking and sorting systems are regulated to distribute these dendritic development factors thro... |
Elementary flux vectors generalize elementary flux modes to handle inhomogeneous linear constraints in metabolic networks. | Elementary flux modes (EFMs) emerged as a formal concept to describe metabolic pathways and have become an established tool for constraint-based modeling and metabolic network analysis. EFMs are characteristic (support-minimal) vectors of the flux cone that contains all feasible steady-state flux vectors of a given met... | A cornerstone of biotechnology is the use of microorganisms for the efficient production of chemicals and the elimination of harmful waste. Pseudomonas putida is an archetype of such microbes due to its metabolic versatility, stress resistance, amenability to genetic modifications, and vast potential for environmental ... |
Geospatial analysis highlights significant regional variations in ANC underutilization across Zambian provinces, with higher education and wealth strongly correlating with better adherence to WHO guidelines. | Antenatal care (ANC) plays a crucial role in preventing and detecting pregnancy risks, facilitating prompt treatment, and disseminating essential information to expectant mothers. This role is particularly vital in developing countries, where a 4.65% rise in maternal mortality rate was observed in 2022, with over 800 m... | Early discharge after child delivery although indispensable, but maybe precluded by several factors. The effect of these factors on prolonged length of stay (LOS) after vaginal delivery has been sparsely investigated in Ghana. This limits understanding of potential leading indicators to inform intervention efforts and ... |
This research explores the impact of specific immunological receptor and ligand interactions on the clinical progression of Mycobacterium leprae. | Background Killer-cell immunoglobulin-like receptors (KIRs) are a group of regulatory molecules able to activate or inhibit natural killer cells upon interaction with human leukocyte antigen (HLA) class I molecules. Combinations of KIR and HLA may contribute to the occurrence of different immunological and clinical res... | The pathways that trigger exacerbated immune reactions in leprosy could be determined by genetic variations. Here, in a prospective approach, both genetic and non-genetic variables influencing the amount of time before the development of reactional episodes were studied using Kaplan–Meier survival curves, and the genet... |
Understanding the structural mechanism of zeta toxins offers a promising pathway for developing new antibiotics against pathogenic bacteria. | Most genomes of bacteria contain toxin–antitoxin (TA) systems. These gene systems encode a toxic protein and its cognate antitoxin. Upon antitoxin degradation, the toxin induces cell stasis or death. TA systems have been linked with numerous functions, including growth modulation, genome maintenance, and stress respons... | The pathogenesis of Clostridium difficile, the major cause of antibiotic-associated diarrhea, is mainly associated with the production and activities of two major toxins. In many bacteria, toxins are released into the extracellular environment via the general secretion pathways. C. difficile toxins A and B have no expo... |
RNAIII represses the synthesis of staphylocoagulase in Staphylococcus aureus by directly binding to its mRNA to block translation. | Staphylococcus aureus RNAIII is the intracellular effector of the quorum sensing system that temporally controls a large number of virulence factors including exoproteins and cell-wall-associated proteins. Staphylocoagulase is one major virulence factor, which promotes clotting of human plasma. Like the major cell surf... | Bacteria utilize endoribonuclease-mediated RNA processing and decay to rapidly adapt to environmental changes. Here, we report that the modulation of hns mRNA stability by the endoribonuclease RNase G plays a key role in Salmonella Typhimurium pathogenicity. We found that RNase G determines the half-life of hns mRNA by... |
Sex-biased isoform switching occurs throughout wasp development, primarily within genes that are already differentially expressed. | Sexual dimorphism requires regulation of gene expression in developing organisms. These developmental differences are caused by differential expression of genes and isoforms. The effect of expressing a gene is also influenced by which other genes are simultaneously expressed (functional interactions). However, few stud... | In the fruit fly Drosophila melanogaster, male-specific splicing and translation of the Fruitless transcription factor (FruM) alters the presence, anatomy, and/or connectivity of >60 types of central brain neurons that interconnect to generate male-typical behaviors. While the indispensable function of FruM in sex-spec... |
A new screening pipeline and metabolic engineering in *Yarrowia lipolytica* achieved a high yield of the antidepressant orcinol glucoside, vastly surpassing plant extraction. | Orcinol glucoside (OG), mainly found in the rhizome of the traditional Chinese herb Curculigo orchioides Gaertn, is noted for its antidepressant effects. In this study, an efficient screening pipeline was established for identifying the highly active orcinol synthase (ORS) and UDP-dependent glycosyltransferase (UGT) in... | Development of cell factories for conversion of lignocellulosic biomass hydrolysates into biofuels or bio-based chemicals faces major challenges, including the presence of inhibitory chemicals derived from biomass hydrolysis or pretreatment. Extensive screening of 2526 Saccharomyces cerevisiae strains and 17 non-conven... |
A FRET-based study demonstrates that the ESX-1 secretion system enables Mycobacterium tuberculosis to rupture phagolysosomes, access the cytosol, and trigger necrotic macrophage death. | Survival within macrophages is a central feature of Mycobacterium tuberculosis pathogenesis. Despite significant advances in identifying new immunological parameters associated with mycobacterial disease, some basic questions on the intracellular fate of the causative agent of human tuberculosis in antigen-presenting c... | In a study of household contacts (HHC), households were categorized into High (HT) and Low (LT) transmission groups based on the proportion of HHC with a positive tuberculin skin test. The Mycobacterium tuberculosis (Mtb) strains from HT and LT index cases of the households were designated Mtb-HT and Mtb-LT, respective... |
This study reports the first clinical trial of a third-generation leishmaniasis vaccine intentionally developed to induce specific CD8+ T cells. | Background Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropri... | Background Leishmaniasis remains a significant cause of morbidity and mortality in the tropics. Available therapies are problematic due to toxicity, treatment duration and emerging drug resistance. Mouse models of leishmaniasis have demonstrated that disease outcome depends critically on the balance between effector an... |
While extreme heat and maternal mortality are well-studied, future research must address overlooked issues like drought, malnutrition, and food insecurity to guide climate-responsive policies. | Climate change poses unique challenges to maternal well-being and increases complications during pregnancy and childbirth globally. This evidence gap map (EGM) aims to identify gaps in existing knowledge and areas where further research related to climate change and its impact on maternal health is required. The follow... | Fear of infection and measures taken to mitigate infection, such as social distancing, lockdown and isolation can lead to anxiety and depression across the life course, but especially in pregnancy. We set out to identify the prevalence of depression in pregnancy, using Edinburgh Postnatal Depression Scale (EPDS) during... |
The impact of drug-resistance mutations on mortality in antiretroviral-naïve patients is poorly understood and requires long-term investigation. | Background The impact of the emergence of drug-resistance mutations on mortality is not well characterized in antiretroviral-naïve patients first starting highly active antiretroviral therapy (HAART). Patients may be able to sustain immunologic function with resistant virus, and there is limited evidence that reduced s... | Antiretroviral therapy (ART) treatment failure remains a major public health concern, with multidimensional consequences, including an increased risk of drug resistance, compromised quality of life, and high healthcare costs. However, little is known about the outcomes of second-line ART in Ethiopia. Therefore, this sy... |
Smoking is inversely associated with genetic VHL inactivation, suggesting that wild-type tumors in current smokers may represent a biologically distinct clinical entity. | Renal tumor heterogeneity studies have utilized the von Hippel-Lindau VHL gene to classify disease into molecularly defined subtypes to examine associations with etiologic risk factors and prognosis. The aim of this study was to provide a comprehensive analysis of VHL inactivation in clear cell renal tumors (ccRCC) and... | We have developed a transcriptome-wide approach to identify genes affected by promoter CpG island DNA hypermethylation and transcriptional silencing in colorectal cancer. By screening cell lines and validating tumor-specific hypermethylation in a panel of primary human colorectal cancer samples, we estimate that nearly... |
Improving diagnostics for under-reported anisakiasis requires comprehensive knowledge of the molecules and allergens expressed by Anisakis parasites. | Background Food-borne nematodes of the genus Anisakis are responsible for a wide range of illnesses (= anisakiasis), from self-limiting gastrointestinal forms to severe systemic allergic reactions, which are often misdiagnosed and under-reported. In order to enhance and refine current diagnostic tools for anisakiasis, ... | Background A better understanding of reproductive processes in parasitic nematodes may lead to development of new anthelmintics and control strategies for combating disabling and disfiguring neglected tropical diseases such as lymphatic filariasis and onchocerciasis. Transcriptomatic analysis has provided important new... |
Reducing neonatal mortality requires managing complications like asphyxia and low birthweight, providing care within the first 24 hours, and ensuring mothers attend at least eight antenatal visits. | Neonatal mortality accounts for nearly half of under-5 mortality in Ghana. The aim of this study was to identify the predictors of neonatal mortality in the Eastern Regional Hospital, Ghana. This was a retrospective cohort study conducted using secondary data from electronic medical records from the Eastern Regional Ho... | Early discharge after child delivery although indispensable, but maybe precluded by several factors. The effect of these factors on prolonged length of stay (LOS) after vaginal delivery has been sparsely investigated in Ghana. This limits understanding of potential leading indicators to inform intervention efforts and ... |
Research indicates that the NS1 protein significantly influences the pathogenicity of Zika virus, revealing distinct biological differences between historical and contemporary African lineages. | Mosquito-borne Zika virus (ZIKV) from sub-Saharan Africa has recently gained attention due to its epidemic potential and its capacity to be highly teratogenic. To improve our knowledge on currently circulating strains of African ZIKV, we conducted protein sequence alignment and identified contemporary West Africa NS1 (... | Background Mosquito-borne Zika virus (ZIKV) typically causes a mild and self-limiting illness known as Zika fever, which often is accompanied by maculopapular rash, headache, and myalgia. During the current outbreak in South America, ZIKV infection during pregnancy has been hypothesized to cause microcephaly and other ... |
A review of dengue transmission control research is essential for shaping effective disease management strategies. | Background Research has been conducted on interventions to control dengue transmission and respond to outbreaks. A summary of the available evidence will help inform disease control policy decisions and research directions, both for dengue and, more broadly, for all Aedes-borne arboviral diseases. | Introduction The first outbreak of dengue in American Samoa was reported in 1911. Sporadic outbreaks have been reported since, as were outbreaks of other pathogens transmitted by Aedes species mosquitoes including Ross River, chikungunya, and Zika viruses. During an outbreak of dengue virus-type 2 (DENV-2) in 2016–2018... |
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