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PubMed2026

A systematic review and meta-analysis to estimate the global prevalence of leptospirosis in sheep.

Leptospirosis in sheep is a zoonotic concern considering sheep may act as potential reservoirs for Leptospira spp. infection to humans. This study aimed to estimate the pooled prevalence of leptospirosis in sheep worldwide. A comprehensive literature search was conducted across databases following PRISMA guidelines. Meta-analyses were performed using a random effect model in R software (version 4.3.1) to calculate pooled prevalence with 95% confidence intervals (CI). Subgroup analyses were performed based on prevalence types, diagnostic methods and continental regions to explore sources of heterogeneity. A total of 138 studies comprising 54,174 samples and 10,299 positive detections were included in this study. The global pooled prevalence of leptospirosis in sheep was 15.69% (95% CI: 12.69-19.25) with overall heterogeneity (I2) 98%. The prediction interval ranged from 1.09% to 75.91%, indicating wide inter-study variability. The seroprevalence was 16.16% (95% CI: 12.91-20.04) and infection prevalence was 12.98% (95% CI: 8.07-20.22), showing no significant difference (P = 0.40). In addition, the prevalence of leptospirosis in sheep differed significantly across diagnostic methods and continents (P < 0.01), indicating substantial variation influenced by both methodological and geographical factors. The funnel plot revealed marked asymmetry, suggesting potential publication bias which was confirmed by Egger's regression test (P < 0.01). In conclusion, leptospirosis is widely prevalent in sheep globally, with marked geographical and methodological heterogeneity. These findings highlight the epidemiological importance of sheep in leptospirosis transmission and underscore the need for improved surveillance, standardized diagnostic approaches, and targeted control strategies within a One Health framework.

Animals↗

PubMed2005

Ground level ozone concentrations at a rural location in northern Spain.

A systematic analysis of surface ozone observations at a rural area of the upper Spanish plateau is presented. A near four-year study of ozone concentrations was carried out between February 2000 and October 2003. Diurnal and monthly variations of ozone are studied. The peak concentration levels are obtained between 13:00 and 15:00 GMT and the lowest levels at 4:00 and 5:00 GMT. The highest values together with a slight increase in data variability are found from April to August, when spring and summer maxima are appreciated. The relationship between synoptic-scale atmospheric transport patterns and the maximum ozone concentrations was also examined. Analysis of the 500-hPa synoptic weather patterns revealed that the highest values occur during continental and Atlantic ridges in summer and, to a lesser extent, during troughs in the east-northeast of the Iberian Peninsula in spring. Our approach entailed calculating 3-day isobaric backward air mass trajectories at the observational site sorted on the following main origins: European continent, African continent, Atlantic Ocean and local. The assessment of the results showed the influence of local conditions on the daily maximum ozone concentrations. Moreover, continental air masses provide certain evidence of long-range transport added to the local or regional contribution of the main cities affecting the sampling site. Conversely, Atlantic trajectories show the least contribution to ozone levels.

Air Movements↗

PubMed2005

Aging and eating in the rural, southern United States: beliefs about salt and its effect on health.

This paper draws upon qualitative research conducted among older adults in the rural, southern United States in which they articulated their beliefs and experiences with nutrition and foods, and lay models of the connection of diet with chronic disease. Salt emerged as a focus of contention. The goals of the paper are to (1) present the culturally constructed meaning of salt, (2) contrast the cultural meaning with biomedical views, and (3) discuss how these findings can be applied to health education and better doctor-patient communication. Data were collected in two rural communities characterized by high rates of poverty and a high proportion of minority residents. A total of 116 African American, Native American and white adults aged 60 years and older participated in 55 in-depth interviews or seven focus groups. A systematic analysis of text showed that salt was a highly contested component of food. While valued for its role in traditional foods and cuisine, it also held negative connotations because of biomedical links to chronic diseases prevalent in the population. We suggest that attempts to control salt intake are made difficult by the changes in taste perceptions that accompany aging. Respondents' articulation of salt's role in health and disease shows cross-over among different chronic diseases and a lay interpretation of blood as the medium through which salt affects disease. These older adults' narratives demonstrate their attempts to reconcile the important role of traditional foods in their identity as Southerners with their attempts to meet medical recommendations for healthy eating.

Black or African American↗

PubMed2006

Marital status and mortality in the elderly: a systematic review and meta-analysis.

Although a relationship between marital status and mortality has long been recognized, no summary estimates of the strength of the association are available. A meta-analysis of cohort studies was conducted to produce an overall estimate of the excess mortality associated with being unmarried in aged individuals as well as to evaluate whether and to what degree the effect of marriage differs with respect to gender, geographical/cultural context, type of non-married condition and study methodological quality. All included studies were published after the year 1994, used multivariate analyses and were written in English. Pooling 53 independent comparisons, consisting of more than 250,000 elderly subjects, the overall relative risk (RR) for married versus non-married individuals (including widowed, divorced/separated and never married) was 0.88 (95% Confidence Interval: 0.85-0.91). This estimate did not vary by gender, study quality, or between Europe and North America. Compared to married individuals, the widowed had a RR of death of 1.11 (1.08-1.14), divorced/separated 1.16 (1.09-1.23), never married 1.11 (1.07-1.15). Although some evidence of publication bias was found, the overall estimate of the effect of marriage was robust to several statistical approaches and sensitivity analyses. When the overall meta-analysis was repeated with an extremely conservative approach and including eight non-significant comparisons, which were initially excluded because of data unavailable, the marriage protective influence remained significant, although the effect size was reduced (RR=0.94; 0.92-0.95). Despite some methodological and conceptual limitations, these findings might be important to support health care providers in identifying individuals "at risk" and could be integrated into the current programs of mortality risk estimation for the elderly.

Aged↗

PubMed2025

ChemPerturb-seq screen identifies a small molecule cocktail enhancing human beta cell survival after subcutaneous transplantation.

Traditional chemical screens have focused on a single assay per screen, making them labor intensive and costly. Here, we combined a chemical screen with single-cell RNA sequencing (scRNA-seq) to perform Chemical Perturb-seq (ChemPerturb-seq), enabling a systematic analysis of the molecular changes of human beta cells upon individual small molecule treatments. Using this platform, we performed an in vivo barcoded screen and discovered a small molecule cocktail, including beta-lipotropin 61-91, insulin growth factor-1, and prostaglandin E2, with which preconditioning human beta cells and primary islets significantly enhanced function and survival when transplanted subcutaneously to female, but not to male, mice. We identified two additional molecules, serotonin and histamine, that promote islet function when transplanted subcutaneously to male mice using ChemPerturb-seq. Such small molecule cocktails could be applied to improve the current FDA-approved islet transplantation procedure. Finally, we developed an artificial intelligence (AI)-powered website, ChemPerturbDB, which provides user-friendly open access analysis of the extensive ChemPerturb-seq dataset.

Humans↗

PubMed2005

Coupling between catalytic site and collective dynamics: a requirement for mechanochemical activity of enzymes.

Growing evidence supports the view that enzymatic activity results from a subtle interplay between chemical kinetics and molecular motions. A systematic analysis is performed here to delineate the type and level of coupling between catalysis and conformational mechanics. The dynamics of a set of 98 enzymes representative of different EC classes are analyzed with the Gaussian network model (GNM) and compared with experimental data. In more than 70% of the examined enzymes, the global hinge centers predicted by the GNM are found to be colocalized with the catalytic sites experimentally identified. Low translational mobility (< 7%) is observed for the catalytic residues, consistent with the fine-tuned design of enzymes to achieve precise mechanochemical activities. Ligand binding sites, while closely neighboring catalytic sites, enjoy a moderate flexibility to accommodate the ligand binding. These findings could serve as additional criteria for assessing drug binding residues and could lessen the computational burden of substrate docking searches.

Binding Sites↗

PubMed2006

Modeling a self-avoiding chromatin loop: relation to the packing problem, action-at-a-distance, and nuclear context.

There is now convincing evidence that genomes are organized into loops, and that looping brings distant genes together so that they can bind to local concentrations of polymerases in "factories" or "hubs." As there remains no systematic analysis of how looping affects the probability that a gene can access binding sites in such factories/hubs, we used an algorithm that we devised and Monte Carlo methods to model a DNA or chromatin loop as a semiflexible (self-avoiding) tube attached to a sphere; we examine how loop thickness, rigidity, and contour length affect where particular segments of the loop lie relative to binding sites on the sphere. Results are compared with those obtained with the traditional model of an (infinitely thin) freely jointed chain. They provide insights into the packing problem (how long genomes are packed into small nuclei), and action-at-a-distance (how firing of one origin or gene can prevent firing of an adjacent one).

Algorithms↗

PubMed2026

Multi-omics panorama of glaucoma: Pathogenesis, biomarkers, and novel therapeutic strategies.

Glaucoma is a group of irreversible, blinding eye diseases characterized by progressive loss of retinal ganglion cells, leading to gradual visual field defects that severely impact patients' quality of life. Its complex pathophysiological mechanisms remain incompletely understood, limiting the development of early diagnostic and effective therapeutic strategies. Advances in omics technologies have provided new insights into elucidating the pathophysiology of glaucoma. We summarize specific alterations in genomics, transcriptomics, proteomics, metabolomics, epigenomics, and microbiomics associated with glaucoma. We emphasize the systematic analysis of disease mechanisms, identification of clinically applicable biomarkers, and discovery of novel therapeutic targets through the integration of these data. This approach paves new pathways for glaucoma subtype diagnosis and personalized treatment, while also outlining future research directions and challenges.

Humans↗

PubMed2006

Developmental toxicity of 4-ring polycyclic aromatic hydrocarbons in zebrafish is differentially dependent on AH receptor isoforms and hepatic cytochrome P4501A metabolism.

Polycyclic aromatic hydrocarbons (PAHs) derived from fossil fuels are ubiquitous contaminants and occur in aquatic habitats as highly variable and complex mixtures of compounds containing 2 to 6 rings. For aquatic species, PAHs are generally accepted as acting through either of two modes of action: (1) "dioxin-like" toxicity mediated by activation of the aryl hydrocarbon receptor (AHR), which controls a battery of genes involved in PAH metabolism, such as cytochrome P4501A (CYP1A) and (2) "nonpolar narcosis", in which tissue uptake is dependent solely on hydrophobicity and toxicity is mediated through non-specific partitioning into lipid bilayers. As part of a systematic analysis of mechanisms of PAH developmental toxicity in zebrafish, we show here that three tetracyclic PAHs (pyrene, chrysene, and benz[a]anthracene) activate the AHR pathway tissue-specifically to induce distinct patterns of CYP1A expression. Using morpholino knockdown of ahr1a, ahr2, and cyp1a, we show that distinct embryolarval syndromes induced by exposure to two of these compounds are differentially dependent on tissue-specific activation of AHR isoforms or metabolism by CYP1A. Exposure of embryos with and without circulation (silent heart morphants) resulted in dramatically different patterns of CYP1A induction, with circulation required to deliver some compounds to internal tissues. Therefore, biological effects of PAHs cannot be predicted simply by quantitative measures of AHR activity or a compound's hydrophobicity. These results indicate that current models of PAH toxicity in fish are greatly oversimplified and that individual PAHs are pharmacologically active compounds with distinct and specific cellular targets.

Abnormalities, Drug-Induced↗

PubMed2005

Post-breeding inflammation and endometrial cytology in mares.

Endometritis has been reported to be the third most common medical condition of horses. Timely diagnosis and treatment of endometritis in mares increases the chance of pregnancy. Exfoliative endometrial cytology is often used as a clinical tool to evaluate endometrial inflammation through detection of neutrophils. There is a lack of information on the time frame for changes in endometrial cytologic parameters following breeding. The main objectives of this article are to use current information to describe systematic analysis of endometrial cytology using standardized methods for sample collection and interpretation, and discuss how these parameters change in relationship to post-breeding interval and mare susceptibility.

Animals↗

PubMed2006

Ultrasound fetal measurements and pregnancy associated glycoprotein secretion in early pregnancy in cattle recipients carrying somatic clones.

Somatic cloning in the bovine species leads to high levels of fetal losses which occur throughout pregnancy. These losses are most often associated with fetal overgrowth, a syndrome known as large offspring syndrome (LOS), and excessive maternal plasma pregnancy serum protein 60 (PSP60), a protein similar to a pregnancy-associated glycoprotein of 67 kDa (PAG I67) produced by the bovine placenta. Predicting the outcome of pregnancies initiated from cloned embryos has become an important issue both to prevent potential harm to the mother because of excessive fetal size at birth and also to get a better understanding of the relationships between growth, differentiation and placental functions in developing cloned fetuses. Here, we report on a systematic analysis of fetal and placental development in the first trimester of pregnancy performed by ultrasonographic imaging and by measurement of the maternal concentrations of pregnancy associated glycoproteins (PAGS), using four different radioimmunoassays (RIA) (two homologous RIA systems with PSP60 and PAG I67; two heterologous RIA systems with PAG I67 as standard and tracer, and antisera anti-caprine PAGs). We showed that crown-rump length (CRL) in clones appeared smaller than controls at 35, 50 and 62 days (P<0.05). At 62 days of pregnancy, CRL in cloned fetuses that died before 90 days was smaller compared to the other cloned fetuses (P<0.05) whereas the width of the fetal sack and the biparietal diameter (BPD) was larger in fetuses that developed LOS in late gestation (P<0.05). Maternal PAGs concentrations were statistically different between controls and all clone recipients as early as Day 34, suggesting early abnormal placental glycoprotein synthesis for clone pregnancies regardless of pregnancy outcome. This work provides a practical, non-invasive tool to follow up clone pregnancies and suggests that primary growth retardation and abnormal placental function precedes excessive fetal and placental growth at later stages of pregnancy.

Animals↗

PubMed2004

The regulatory software of cellular metabolism.

Understanding the regulation of metabolic pathways in the cell is like unraveling the 'software' that is running on the 'hardware' of the metabolic network. Transcriptional regulation of enzymes is an important component of this software. A recent systematic analysis of metabolic gene-expression data in Saccharomyces cerevisiae reveals a complex modular organization of co-expressed genes, which could increase our ability to understand and engineer cellular metabolic functions.

Algorithms↗

PubMed2006

Cloned sequence repertoires for small- and large-scale biology.

How to assign function to the tens of thousands of genes discovered in the chromosomes of a few model species? How to complement the classical genetic approaches that are not always ideally suited to decode complex mechanisms? The solutions to these pressing questions are not simple and rely on the development of novel resources and technologies. Here I critically review what clone collections are available and how they can be exploited for the systematic analysis of gene functions in plants.

Cloning, Molecular↗

PubMed2006

HIV-1 DNA/MVA vaccination reduces the per exposure probability of infection during repeated mucosal SHIV challenges.

Historically, HIV vaccines specifically designed to raise cellular immunity resulted in protection from disease progression but not infection when tested in monkeys challenged with a single high virus exposure. An alternative approach, more analogous to human sexual exposures, is to repetitively challenge immunized monkeys with a much lower dose of virus until systemic infection is documented. Using these conditions to mimic human sexual transmission, we found that a multi-protein DNA/MVA HIV-1 vaccine is indeed capable of protecting rhesus monkeys against systemic infection when repeatedly challenged with a highly heterologous immunodeficiency virus (SHIV). Furthermore, this repetitive challenge approach allowed us to calculate per-exposure probability of infection, an observed vaccine efficacy of 64%, and undertake a systematic analysis for correlates of protection based on exposures needed to achieve infection. Therefore, improved non-human primate models for vaccine efficacy can provide novel insight and perhaps renew expectations for positive outcomes of human HIV clinical trials.

AIDS Vaccines↗

PubMed2005

Influence of the sediment on lead speciation in the Tagus estuary.

The aim of this work is to study the influence of the Tagus estuarine sediment on lead speciation in the overlying natural water. The water sample in the presence of the sediment was contaminated three times with Pb(II) in a laboratory experiment. In different periods of time, at 1-7 days after each contamination, small volumes of water were titrated with lead. The titration was followed by anodic stripping voltammetry in differential pulse mode. Before and after contamination systematic analysis of the voltammetric parameters (peak current, peak potential and peak width) were carried out to get a clear picture of Pb(II) complexation in the soluble fraction in contact with the sediment. Two main types of organic ligands, macromolecular ligands and small compounds, were detected before contamination. Both of them form labile complexes (degree of lability within the timescale of some milliseconds). The small compounds, with a diffusion coefficient similar to that of the free metal ion, present a homogeneous behaviour in terms of Pb complexation. On the other hand macromolecular ligands, with a diffusion coefficient of 1.2 x 10(-6) cm2s(-1), can be described by two different binding groups, which might be of phenolic and carboxylic type as presented by humic matter. The sediment eliminated lead contamination (10(-6) moldm(-3) was the maximum concentration added) from 12 dm3 of water (surface of 8 dm2) within 2 days. It was also found that the sediment released organic ligands responsible for both labile and inert Pb complexes "seen" by voltammetry. The release of organic ligands that decreases the bioavailability of Pb(II) was clearly detected 1 week after contamination. Therefore, the sediment acts as a buffer for lead through two mechanisms against lead contamination: removing lead ions from the solution and releasing organic ligands to the water column. In a short period of time the sediment responds as a self-cleaning system for Pb(II) contamination in the estuarine water, which may have a very important influence in environmental pollution.

Diffusion↗

PubMed2006

Atrioventricular valve development during late embryonic and postnatal stages involves condensation and extracellular matrix remodeling.

Although the signaling molecules regulating the early stages of valvular development have been well described, little is known on the late steps leading to mature fibrous leaflets. We hypothesized that atrioventricular (AV) valve development continues after birth to adjust to the postnatal maturation of the heart. By doing a systematic analysis of the AV valves of mice from embryonic day (E) 15.5 to 8 weeks old, we identified key developmental steps that map the maturation process of embryonic cushion-like leaflets into adult stress-resistant valves. Condensation of the mesenchymal cells occurred between E15.5 and E18.5 and was accompanied by increased cellular proliferation and adhesion. Cellular proliferation also contributed transiently to the concomitant elongation of the leaflets. Patterning of the extracellular matrix (ECM) proteins along the AV axis was achieved 1 week after birth, with the differentiation of two reciprocal structural regions, glycosaminoglycans and versican at the atrial side, and densely packed collagen fibers at the ventricular side. Formation and remodeling of the nodular thickenings at the closure points of the leaflets occurred between N4.5 and N11.5. In conclusion, AV valve development during late embryonic and postnatal stages includes condensation, elongation, formation of nodular thickenings, and remodeling of tension-resistant ECM proteins.

Animals↗

PubMed2006

Cooperation of sonic hedgehog enhancers in midline expression.

In zebrafish, as in other vertebrates, the secreted signalling molecule Sonic hedgehog (Shh) is expressed in organiser regions such as the embryonic midline and the zona limitans intrathalamica (zli). To investigate the regulatory mechanisms underlying the pattern of shh expression, we carried out a systematic analysis of the intronic regulatory sequences of zebrafish shh using stable transgenesis. Deletion analysis identified the modules responsible for expression in the embryonic shield, the hypothalamus and the zli and confirmed the activities of previously identified notochord and floor plate enhancers. We detected a strong synergism between regulatory regions. The degree of synergy varied over time in the hypothalamus suggesting different mechanisms for initiation and maintenance of expression. Our data show that the pattern of shh expression in the embryonic central nervous system involves an intricate crosstalk of at least 4 different regulatory regions. When compared to the enhancer activities of the mouse Shh gene, we observed a remarkable divergence of function of structurally conserved enhancer sequences. The activating region ar-C (61% identical to SFPE2 in mouse Shh), for example, mediates floor plate expression in the mouse embryo while it directs expression in the forebrain and the notochord and only weakly in the floor plate in the zebrafish embryo. This raises doubts on the predictive power of phylogenetic footprinting and indicates a stunning divergence of function of structurally conserved regulatory modules during vertebrate evolution.

Animals↗

PubMed2004

Laminin isoforms: biological roles and effects on the intracellular distribution of nuclear proteins in intestinal epithelial cells.

Laminins are structurally and functionally major components of the extracellular matrix. Four isoforms of laminins (laminin-1, -2, -5 and -10) are expressed in a specific pattern along the crypt-villus axis of the intestine. Previous works indicated that expression of these isoforms is developmentally regulated and that laminins could modulate the behaviour of intestinal cells, but the exact role of each isoform remained unclear. Here, we report the first systematic analysis of the cellular functions of the four isoforms using the human colon adenocarcinoma Caco2/TC7 cell line as a model. We compared the respective abilities of each isoform to modulate adhesion, proliferation and differentiation of intestinal epithelial cells. We found that the isoforms were functionally distinct, with laminin-10 being the most adhesive substratum, laminin-2, laminin-5 and laminin-10 enhancing cellular proliferation and at the opposite, laminin-1 stimulating intestinal cell differentiation. To begin to characterise the molecular events induced by the different isoforms, we examined by immunofluorescence the intracellular distribution of several nuclear proteins, recently highlighted by a nuclear proteomic approach. We observed clear nucleocytoplasmic redistribution of these proteins, which depended on the laminin isoform. These results provide evidence for a distinct functional role of laminins in intestinal cell functions characterised by specific localisation of nuclear proteins.

Base Sequence↗