Evaluation of a HIV screening strategy in the hospital setting to reduce undiagnosed infection.

INTRODUCTION: In Spain, half of new HIV diagnoses are late and a significant proportion of people living with HIV have not yet been diagnosed. Our aim was to evaluate the effectiveness of an automated opportunistic HIV screening strategy in the hospital setting. METHODS: Between April 2022 and September 2023, HIV testing was performed on all patients in whom a hospital admission analytical profile, a pre-surgical profile and several pre-designed serological profiles (fever of unknown origin, pneumonia, mononucleosis, hepatitis, infection of sexual transmission, rash, endocarditis and myopericarditis) was requested. A circuit was started to refer patients the specialists. RESULTS: 6407 HIV tests included in the profiles were performed and 18 (0.3%) new cases were diagnosed (26.4% of diagnoses in the health area). Five patients were diagnosed by hospital admission and pre-surgery profile and 13 by a serological profile requested for indicator entities (fever of unknown origin, sexually transmitted infection, mononucleosis) or possibly associated (pneumonia) with HIV occult infection. Recent infection was documented in 5 (27.8%) patients and late diagnosis in 9 (50.0%), of whom 5 (55.5%) had previously missed the opportunity to be diagnosed. CONCLUSIONS: This opportunistic screening was profitable since the positive rate of 0.3% is cost-effective and allowed a quarter of new diagnoses to be made, so it seems a good strategy that contributes to reducing hidden infection and late diagnosis.

Fetal Programming Influence on Microbiome Diversity and Ruminal and Cecal Epithelium in Beef Cattle.

We explored the influence of maternal nutritional strategies on the development of the rumen and cecum in offspring. Additionally, we investigated the potential repercussions of prenatal nutrition on the rumen and fecal microbiota composition, utilizing metagenomic 16S techniques, to understand the effects of fetal programming (FP) in Nellore cattle. A total of 63 bulls submitted to different prenatal nutrition strategies, namely, non-programming (NP), partial programming (PP), and complete programming (CP), were evaluated. The rumen epithelium was methodically evaluated based on the presence of rumenitis and structural irregularities. The assessment of cecum lesions was conducted post-evisceration, whereby all thoroughly cleaned ceca were methodically evaluated. Samples from 15 animals of rumen fluid at slaughter and feces during the finishing phase were collected, respectively. All DNA extraction were carried out using the Macherey Nagel NucleoSpin Tissue®, and 16S sequencing was conducted using the V4 primers on the MiSeq platform. Within the ruminal ecosystem, an estimated range of 90 to 130 distinct amplicon sequence variants was discerned, as distributed across 45,000 to 70,000 sequencing reads. Our metagenomic exploration unveils microbial communities that distinctly mirror gastrointestinal tract microenvironments and dietary influences. In sum, this comprehensive study advances our comprehension of FP, highlighting the interplay of maternal nutrition, gastrointestinal development, and microbial communities, contributing significantly to the fields of animal science.

Evaluation of cellular viability in chitosan/L-arginine hydrogels.

BACKGROUND: There is a lack of studies evaluating the toxicity of nitric oxide (NO) precursors in chitosan/L-arginine hydrogels and their topical administration. However, clarifying the characteristics of these elements is essential for their possible use in non-surgical techniques of tooth movement acceleration. Such characteristics include interaction with different cell types, metabolism and drug safety. OBJECTIVES: This in vitro study aimed to assess the cytotoxicity of chitosan hydrogels on human HeLa cells using different concentrations of L-arginine. MATERIAL AND METHODS: The hydrogels were synthesized in a materials engineering laboratory, with a controlled environment, using 4 different L-arginine concentrations of 0%, 10%, 15%, and 20%. Once the hydrogels were prepared, their physical and chemical properties were characterized, and viability analysis was performed using 2 different methods, including a 48-h assay with Artemia salina nauplii and a 24-h cell culture with human HeLa cells followed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) proliferation assay. Data analysis was performed using a Mann-Whitney U test to evaluate positive and negative controls in the cell culture, with a significance level of 0.01. A Wilcoxon paired test contrasted the 24-h compared to 48-h Artemia salina assays, with a Kruskal-Wallis and post hoc Dunn test used to compare groups using a significance level of 0.05. RESULTS: In the more viscous hydrogels, Artemia salina nauplii decreased drastically in 24 h, while the 15% and 20% hydrogels had no statistical differences from the negative control. The 10% and 20% hydrogels were statistically different from the negative control when comparing cell culture data. CONCLUSIONS: Our findings suggest that chitosan/L-arginine hydrogels could be used in humans without toxic effects. However, more trials and tests are needed to evaluate tooth movement rate during orthodontic treatment.

Evaluation of Muscle Long Non-Coding RNA Profile during Rearing and Finishing Phase of Bulls Subjected to Different Prenatal Nutritional Strategies.

Maternal nutrition has the ability of influence critical processes in fetal life, including muscle development. Also, in this period, epigenetic sensitivity to external stimuli is higher and produces long-lasting effects. Thus, the aim of this study was to investigate epigenetic mechanisms, including the identification and characterization of long non-coding RNA (lncRNA) from animals that had undergone different strategies of prenatal supplementation. A group of Nellore cows (n = 126) were separated into three nutritional plans: NP (control)-Not Programmed, without protein-energy supplementation; PP-Partially Programmed, protein-energy supplementation in the final third of pregnancy; and CP-Complete Programming, protein-energy supplementation during the full period of gestation. A total of 63 male offspring were used in this study, of which 15 (5 per treatment) had Longissimus thoracis muscle at 15 (biopsy) and 22 months (slaughter). Biopsy samples were subjected to RNA extraction and sequencing. Differential expression (DE) of remodeling factors and chromatin-modifying enzyme genes were performed. For the identification and characterization of lncRNA, a series of size filters and protein coding potential tests were performed. The lncRNAs identified had their differential expression and regulatory potential tested. Regarding DE of epigenetic mechanisms, no differentially expressed gene was found (p > 0.1). Identification of potential lncRNA was successful, identifying 1823 transcripts at 15 months and 1533 at 22 months. Among these, four were considered differentially expressed between treatments at 15 months and 6 were differentially expressed at 22 months. Yet, when testing regulatory potential, 13 lncRNAs were considered key regulators in the PP group, and 17 in the CP group. PP group lncRNAs possibly regulate fat-cell differentiation, in utero embryonic development, and transforming growth factor beta receptor, whereas lncRNA in the CP group regulates in utero embryonic development, fat-cell differentiation and vasculogenesis. Maternal nutrition had no effect on differential expression of epigenetic mechanisms; however, it seems to impair lncRNA regulation of epigenetics.

Mechanism of escape from the antibacterial activity of metal-based nanoparticles in clinically relevant bacteria: A systematic review.

The emergency of antibiotic-resistant bacteria in severe infections is increasing, especially in nosocomial environments. The ESKAPE group is of special importance in the groups of multi-resistant bacteria due to its high capacity to generate resistance to antibiotics and bactericides. Therefore, metal-based nanomaterials are an attractive alternative to combat them because they have been demonstrated to damage biomolecules in the bacterial cells. However, there is a concern about bacteria developing resistance to NPs and their harmful effects due to environmental accumulation. Therefore, this systematic review aims to report the clinically relevant bacteria that have developed resistance to the NPs. According to the results of this systematic review, various mechanisms to counteract the antimicrobial activity of various NP types have been proposed. These mechanisms can be grouped into the following categories: production of extracellular compounds, metal efflux pumps, ROS response, genetic changes, DNA repair, adaptative morphogenesis, and changes in the plasma membrane.

Fetal Programming and Its Effects on Meat Quality of Nellore Bulls.

This work aimed to evaluate the effects of prenatal nutritional stimulation at different pregnancy stages on carcass traits and meat quality in bovine progeny. For this purpose, 63 Nellore bulls, born from cows submitted to three nutritional plans, were used: not programmed (NP), which did not receive protein supplementation; partially programmed (PP), which had protein-energy supplementation (0.3% of mean body weight of each batch) only in the final third of pregnancy; and full programming (FP), which received supplementation (0.3% of mean body weight of each batch) throughout pregnancy. The averages of parameters were submitted to the ANOVA, and the supplementation periods, which were different when p value < 0.05, were compared. Carcass weights and rib eye area (REA) did not differ between treatments (p > 0.05), but subcutaneous fat thickness (SFT) showed a tendency (p = 0.08) between groups. For lipids and marbling, no differences were found (p > 0.05). In the analyses of maturation time and shelf life, no difference was observed between treatments. However, there was a tendency between treatments at 14 days of maturation time for cooking loss (CL) (p = 0.08). Treatments did not affect shear force in the progenies (p > 0.05). Fetal programming had no effect on the meat quality of Nellore bulls.

Impact of COVID-19 on Dental Practices in El Salvador and Mexico: A Comprehensive Survey Analysis.

BACKGROUND AND OBJECTIVES: This study aimed to identify the relationship between prevention measures and protective barriers in dental practice in El Salvador and Mexico during the COVID-19 pandemic in 2020 and 2021. MATERIALS AND METHODS: A longitudinal study was conducted from June 2020 to December 2021, involving 1,719 dentists divided into four groups based on location and year. A 20-question survey in Spanish was utilized and validated with a Cronbach's alpha value of 0.84. RESULTS: The use of phone triage (OR = 1.3), thermometers (OR = 1.4), physical distancing (OR = 1.7), and face shields (OR = 2.6) was significantly associated with dental practice in both countries during the pandemic. CONCLUSIONS: During 2020 and 2021, dental care in El Salvador and Mexico was significantly linked to COVID-19 preventive measures. Phone triage, thermometers, distancing, and face shields positively correlated with dental services. National health agencies should promote the use of minimum preventive measures in dental care, preparing for potential reinfections or new pandemics from emerging virus variants.

Effects of early weaning on the reproductive performance of suckled Nelore cows in the subsequent breeding season.

This study aimed to evaluate the effects of early weaning (EW) on body composition, hormone concentrations and metabolites, and reproductive performance of Nelore cows in the subsequent breeding season (BS). Suckled cows that became pregnant by timed-AI (TAI) in the 2020-BS were exposed in 2021 to early weaning at 150 d (27 primiparous [PRI] and 74 multiparous [MUL]) or conventional weaning (CW) at 240 d postpartum (30 PRI and 77 MUL). Body weight (BW) and body condition score (BCS) were determined at 2020-BS, EW, CW, prepartum, and 2021-BS. Blood samples were collected at EW, CW, prepartum (54.75 ±â€…0.56 d prepartum), and 2021-TAI and assayed for insulin-like growth factor-1 (IGF-I), non-esterified fatty acid (NEFA), and ß-hydroxybutyrate (BHB) concentrations. In 2021-BS, cows were exposed to a P4/E2-based protocol for TAI at day 0 (D0), and a second TAI was performed at D22 in females detected with luteolysis (D20) by Doppler ultrasound. The presence of corpus luteum (CL) on D10, estrous expression, and dominant follicle (DF) diameter, and blood perfusion (BP) on D2 and D0 were determined. Data were analyzed by ANOVA or logistic regression of SAS as a 2 × 2 factorial with main factors of parity (PRI or MUL) and weaning strategy (EW or CW). An interaction of parity and weaning strategy was not observed (P > 0.1), but the weight (kg) and BCS were greater (P < 0.05) in MUL cows at the five timepoints, and EW cows were heavier than CW at the moment of CW (541 vs. 493 kg; and 5.3 vs. 4.3), prepartum (551 vs. 506 kg; and 5.2 vs. 4.4) and 2021-BS (475 vs. 450 kg; and 4.5 vs. 3.7). Plasma urea concentration at 2021-BS was greater (P = 0.01) for PRI than for MUL. A parity-by-time interaction was observed (P ≤ 0.05) for concentrations of IGF-I, NEFA, and BHB. PRI cows had greater (P ≤ 0.05) concentrations of IGF-I at EW and greater (P ≤ 0.05) prepartum concentrations of NEFA and BHB than MUL cows. The proportion of cows with CL at D10 was not affected (P > 0.1) by weaning but was greater (P < 0.05) in MUL than in PRI cows (40.4 vs. 15.7%). The diameter of DF and proportion of BP on D0 were greater (P < 0.05) in EW cows than in CW cows. The pregnancy rate (P/AI, %) at the first TAI was greater (P < 0.05) in EW cows (60% vs. 45%), whereas no difference (P > 0.1) was observed at the second TAI. Cumulative P/AI (first and second TAIs) was greater (P < 0.05) in EW cows (81% vs. 63%). In conclusion, weaning at 150 d in Nelore cattle is a strategy to successfully recover the parous cow's body condition and to improve pregnancy success in the next BS, regardless of the cow's parity order.

The nutritional condition and body energy reserves at parturition are important factors that can affect the reproductive performance of suckled Nelore cows. Also, decreasing the weaning time can benefit the cow's metabolic status. The present study evaluated the effect of two periods of weaning (150 vs. 240 d) on the reproductive performance of the Nelore dam in the subsequent breeding season. The results of the present study indicate that early weaning: 1) improves the body condition, rump fat thickness, and metabolic condition of Nelore cows for the subsequent breeding season; 2) provides better ovarian follicle growth and blood perfusion during the subsequent timed artificial insemination program; 3) enhances the pregnancy rates in the subsequent breeding season.

Evaluation of Maternal Nutrition Effects in the Lifelong Performance of Male Beef Cattle Offspring.

This study aimed to evaluate the effects of different prenatal nutrition treatments on pregnant cows and their progeny. One hundred and twenty-six pregnant Nellore cows (455.3 ± 8.1 kg) were allocated in three different nutritional treatments during pregnancy: NP-control, PP-protein-energy supplementation in the last 3 months of pregnancy, and FP-the same supplementation throughout pregnancy. After parturition, all cows and calves received the same environmental and nutrition condition. The body condition score (BCS), body weight (BW), ribeye area (REA), backfat thickness (BFT), and rumpfat thickness (RFT) were collected on four occasions during pregnancy in the cows and from birth to finishing in calves. All data (cows and calves) were submitted to an analysis of variance (p < 0.05) using a linear model (MIXED procedure; SAS software). The BW, RFT, and BCS from the cows showed significant differences in the middle third of pregnancy and pre-delivery and RFT postpartum (p < 0.05). For the offspring, the weaning weight showed a tendency (NP lighter than others). In terms of gain, the PP group tended to be higher in RFT at calving (p = 0.06), in REA at finishing (p = 0.09), and in ADG in the same period (p = 0.09). The prenatal nutrition strategies had little or no effect on the beef cattle postnatal performance.

Subgingival Microbiota and Periodontal Clinical Status in Patients with Plaque Psoriasis: A Cross-Sectional Study.

Plaque Psoriasis (PP) and periodontitis are inflammatory disorders with a bidirectional association. They both have a qualitatively similar immune-modulatory cascade, cytokine profile, and a recently described dysbiosis. Different oral bacterial species compositions in the periodontal pocket might play a role in the development of PP. To describe the subgingival microbiota of the Mexican population with PP and the periodontal conditions. Subjects were divided into two groups: periodontal health (PH) (PH-non-PP, PH-PP) and periodontitis (PD) (P-non-PP, PD-PP). Following clinical examination, the patients were classified into three groups according to the degree of psoriasis as measured by the Psoriasis Area Severity Index (PASI) and the periodontal status according to the parameters of the American Academy of Periodontology (AAP). Subgingival microbiota samples of each patient were used to determine 40 species of periodontal bacteria by checkerboard DNA-DNA hybridization. IL-2 and IL-6 were measured by ELISA. Of the forty-eight patients with PP, 21 patients had PH and 27 patients had PD. PD-PP group has a significant increase in the percentage of plaque, gingival redness, pocket probing depth, and clinical attachment loss (P<0.001) compared to PH-PP group. Microbiologically PD-PP exhibited significantly higher mean counts for A. georgiae, A. israelii, A. naeslundii from blue complex (P<0.001) than PD-non-PP. Moreover, the counts of these Actinomyces in PD-PP increased according to the severity of index PASI. The concentration of IL-2 and IL-6 were increased in saliva from PH-PP and PD-PP patients compared to PH non-PP. PP individuals harbored a particular sub-gingival microbiota profile different from non-PP. The severity of psoriasis was related to dysbiosis of microbiota -PASI > 5 related to periodontitis with the predominance of Actinomyces periodontal, irrespective of their periodontal condition. Finally, the severity of psoriasis could be unbalanced in subgingival microbiota and increase the risk to develop periodontitis.

Depression and opinion of dental students regarding the hybrid learning model during the COVID-19 pandemic.

BACKGROUND: The global spread of COVID-19 forced schools at all educational levels to close, which was repeated in more than 60 countries. In addition, the COVID-19 pandemic has affected the mental health of dental students world wide. This study hypothesizes that the prevalence of depression in dental students from El Salvador is higher than that reported in studies from Europe, Asia, and North America. METHODS: This study was an online cross-sectional survey performed at the Faculty of Dentistry of the University of Salvador. The PHQ-9 questionnaire was applied to know the level of depression of the students, and a questionnaire focused on learning the opinion of the students on the hybrid teaching model adopted. Approximately 450 students participated in both questionnaires. RESULTS: Regarding the levels of depression present in the students, 14% had minimal depression, 29% had medium depression, 23% had moderate depression and, 34% had severe depression. The students had an excellent opinion regarding the hybrid learning model. CONCLUSIONS: The prevalence of depression in dental students in El Salvador seems to be higher than that reported in studies in non-Latin American countries. Therefore, universities must generate care plans for mental health to avoid these harmful effects on students during future contingencies.

Impacts of Different Prenatal Supplementation Strategies on the Plasma Metabolome of Bulls in the Rearing and Finishing Phase.

This study investigated the effects of maternal nutrition on the plasma metabolome of Nellore bulls in the rearing and finishing phases, and metabolic differences between these phases. For this study, three nutritional approaches were used in 126 cows during pregnancy: NP-(control) mineral supplementation; PP-protein-energy supplementation in the final third; and FP-protein-energy supplementation during the entire pregnancy. We collected blood samples from male offspring in the rearing (450 ± 28 days old) and finishing phases (660 ± 28 days old). The blood was processed, and from plasma samples, we performed the targeted metabolome analysis (AbsoluteIDQ® p180 Kit). Multiple linear regression, principal component analysis (PCA), repeated measures analysis over time, and an enrichment analysis were performed. PCA showed an overlap of treatments and time clusters in the analyses. We identified significant metabolites among the treatments (rearing phase = six metabolites; finishing phase = three metabolites) and over time (21 metabolites). No significant metabolic pathways were found in the finishing phase, however, we found significant pathways in the rearing phase (Arginine biosynthesis and Histidine metabolism). Thus, prenatal nutrition impacted on plasma metabolome of bulls during the rearing and finishing phase and the different production stages showed an effect on the metabolic levels of bulls.

High body energy reserve influences extracellular vesicles miRNA contents within the ovarian follicle.

Aiming to evaluate the effects of increased body energy reserve (BER) in Nellore cows' reproductive efficiency, cows were fed with different nutritional plans to obtain animals with high BER (HBER; Ad libitum diet) and moderate BER (MBER: cows fed 70% of HBER group ingestion). To evaluate the BER, cows were weekly weighted and evaluated for subcutaneous fat thickness and insulin serum concentration along the experimental period. At the end of the experimental period, animals were submitted to estrous synchronization and artificial insemination. Animals were slaughtered approximately 120 h after ovulation induction and the reproductive tracts were collected for embryo recovery and samples collection. Cumulus-oocyte-complexes (COC) and follicular fluid were collected from 3-6 mm in diameter ovarian follicles to perform miRNA analysis of cumulus cells (CC) and extracellular vesicles from follicular fluid (EV FF). As expected, differences were observed among MBER and HBER groups for body weight, fat thickness, and insulin serum concentration. HBER animals showed lower ovulation and embryo recovery rates compared to MBER animals. Different miRNAs were found among CC and EV FF within groups, suggesting that the BER may influence follicular communication. This suggests that small follicles (3-6 mm diameter) are already under BER effects, which may be greater on later stages of follicular development.

Osteoregeneration of Critical-Size Defects Using Hydroxyapatite-Chitosan and Silver-Chitosan Nanocomposites.

Bone is a natural nanocomposite composed of proteins and minerals that can regenerate itself. However, there are conditions in which this process is impaired, such as extensive bone defects and infections of the bone or surrounding tissue. This study evaluates the osteoregenerative capacity of bone grafting materials in animals with induced bone defects. Colloidal chitosan dispersion nanocomposites, nanohydroxyapatite−chitosan (NHAP-Q) and nanosilver−chitosan (AgNP-Q), were synthesized and characterized. Non-critical-size defects in Wistar rats were used to evaluate the material's biocompatibility, and critical-size defects in the calvarias of guinea pigs were used to evaluate the regenerative capacity of the bones. Moreover, the toxicity of the nanocomposites was evaluated in the heart, liver, spleen, kidneys, and skin. Histological, radiographic, and electron microscopy tests were also performed. The results showed that neither material produced pathological changes. Radiographic examination showed a significant reduction in defects (75.1% for NHAP-Q and 79.3% for AgNP-Q), angiogenesis, and trabecular formation. A toxicological assessment of all the organs did not show changes in the ultrastructure of tissues, and the distribution of silver was different for different organs (spleen > skin > heart > kidney > liver). The results suggest that both materials are highly biocompatible, and AgNP-Q achieved similar bone regeneration to that reported with autologous bone. The main research outcome of the present study was the combination of two types of NPs to enhance antimicrobial and osteoregeneration activities. These colloidal chitosan dispersions show promise as future biomaterials in the medical field for applications in fast-healing fractures, including broken bones in the oral cavity and hip replacement infections.

Different prenatal supplementation strategies and its impacts on reproductive and nutrigenetics assessments of bulls in finishing phase.

This study investigated the effect of different prenatal nutrition approaches in 126 pregnant Nellore cows on reproductive and nutrigenetic traits of the male offspring during the finishing phase. For that purpose, three nutritional treatments were used in these cows during pregnancy: PP - protein-energy supplementation in the final third, FP - protein-energy supplementation during the entire pregnancy, and NP - (control) only mineral supplementation. The male progeny (63 bulls; 665 ± 28 days of age) were evaluated for scrotal circumference, seminal traits, number of Sertoli cells and testicular area. We performed a genomic association (700 K SNPs) for scrotal circumference at this age. In addition, a functional enrichment was performed in search of significant metabolic pathways (P < 0.05) with inclusion of genes that are expressed in these genomic windows by the MetaCore software. With the exception of major sperm defects (P < 0.1), the other phenotypes showed no difference between prenatal treatments. We found genes and metabolic pathways (P < 0.05) that are associated with genomic windows (genetic variance explained >1%) in different treatments. These molecular findings indicate that there is genotype-environment interaction among the different prenatal treatments and that the FP treatment showed greater major sperm defects compared to the NP treatment.

Metabolomics Changes in Meat and Subcutaneous Fat of Male Cattle Submitted to Fetal Programming.

This study investigated changes in meat and subcutaneous fat metabolomes and possible metabolic pathways related to prenatal nutrition in beef cattle. For this purpose, 18 Nellore bulls were used for meat sampling and 15 for fat sampling. The nutritional treatments during the gestation were: NP-not programmed or control, without protein-energy supplementation; PP-partially programmed, with protein-energy supplementation (0.3% of body weight (BW)) only in the final third of pregnancy; and FP-full programming, with protein-energy supplementation (0.3% of BW) during the entire pregnancy. The meat and fat samples were collected individually 24 h after slaughter, and the metabolites were extracted using a combination of chemical reagents and mechanical processes and subsequently quantified using liquid chromatography or flow injection coupled to mass spectrometry. The data obtained were submitted to principal component analysis (PCA), analysis of variance (ANOVA), and functional enrichment analysis, with a significance level of 5%. The PCA showed an overlap between the treatments for both meat and fat. In meat, 25 metabolites were statistically different between treatments (p ≤ 0.05), belonging to four classes (glycerophospholipids, amino acids, sphingolipids, and biogenic amine). In fat, 10 significant metabolites (p ≤ 0.05) were obtained in two classes (phosphatidylcholine and lysophosphatidylcholine). The functional enrichment analysis showed alterations in the aminoacyl-tRNA pathway in meat (p = 0.030); however, there was no pathway enriched for fat. Fetal programming influenced the meat and fat metabolomes and the aminoacyl-tRNA metabolic pathway, which is an important candidate for the biological process linked to meat quality and related to fetal programming in beef cattle.

Maternal Nutrition Affects Nitrogen Isotopic Signature in Blood Plasma of Beef Cattle Dams and Their Offspring.

This study evaluated the effects of gestational supplementation strategy on nitrogen isotopic signature in blood plasma of beef cows and their progeny. The study comprised 15 pregnant Nellore cows divided into three different supplementation protocols: NP) non-programmed group; PP) cows receiving protein−energy supplement in the last third of pregnancy; and FP) cows receiving protein−energy supplement throughout the gestational period. Blood plasma from cows was sampled at the beginning of gestation, in the prepartum, and postpartum periods as well as from their calves at 30 and 180 days of age, for the analysis of stable isotope ratios 15 N/14 N. At pre- and postpartum periods, cows fed PP and FP presented greater abundance of δ15 N compared to NP (p < 0.05) at pre- and postpartum. All three groups showed significant differences (p < 0.05) in the postpartum period. The δ15 N values of calves at 30 days of age differed between the NP group and PP and FP groups (p < 0.05), with no difference (p > 0.05) at 180 days of age. The different gestational supplementation strategies influenced isotopic fractionation of nutrients of cows and their calves after birth, indicating effects on nutritional metabolism and cumulative behavior on isotope abundance related to consumption during gestation.

GPC3-Unc5 receptor complex structure and role in cell migration.

Neural migration is a critical step during brain development that requires the interactions of cell-surface guidance receptors. Cancer cells often hijack these mechanisms to disseminate. Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. In the complex, four Unc5D molecules pack into an antiparallel bundle, flanked by four GPC3 molecules. Central glycan-glycan interactions are formed by N-linked glycans emanating from GPC3 (N241 in human) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains. MD simulations, mass spectrometry and structure-based mutants validate the crystallographic data. Anti-GPC3 nanobodies enhance or weaken Unc5-GPC3 binding and, together with mutant proteins, show that Unc5/GPC3 guide migrating pyramidal neurons in the mouse cortex, and cancer cells in an embryonic xenograft neuroblastoma model. The results demonstrate a conserved structural mechanism of cell guidance, where finely balanced Unc5-GPC3 interactions regulate cell migration.

Identification of eQTLs and differential gene expression associated with fetal programming in beef cattle.

This study assessed differential gene expression and identified expression quantitative trait loci (eQTLs) from samples of Longissimus lumborum muscle from bulls at 15 months of age submitted to different prenatal nutrition. Upon confirmation of pregnancy, 126 dams were separated into three diet treatments varying the period of inclusion of energy protein supplementation (NP, PP, and FP). At calving, 63 males were genotyped with GGP LD BeadChip. The skeletal muscle of 15 bulls was sequenced (RNA-seq) at 15 months of age. The EdgeR package was used for differential gene expression and principal component analysis (PCA), and the Matrix eQTL package was used for the eQTLs analysis (R statistical). The functional enrichment analysis was performed using the MetaCore® software. No genes differentially expressed were found between treatments (FDR > 0.05); nevertheless, we found 179 cis-tag-eQTLs and 20,762 trans-tag-eQTLs (FDR < 0.05) after linkage disequilibrium analysis. The functional enrichment analysis identified terms from gene ontology related to genes associated to trans-eQTLs (FDR < 0.05) as well as metabolic pathways (> gScore). Most biological pathways and genes found had been previously associated to fetal programming. The different prenatal supplementation strategies did not impact on muscle transcriptome of bulls. Additionally, there is a link between genotype and gene expression levels related to developmental traits in Nellore cattle.

Effects of Different Prenatal Nutrition Strategies on the Liver Metabolome of Bulls and Its Correlation with Body and Liver Weight.

This study investigated the effect of prenatal nutrition on liver metabolome and on body (BW) and liver weight (LW) of Nellore bulls at slaughter. Three treatments were applied in 126 cows during pregnancy: NP­control (mineral supplementation); PP­protein-energy supplementation in the third trimester; and FP­protein-energy supplementation during the entire pregnancy. Offspring BW and LW were evaluated, and a targeted metabolomics analysis was performed on their livers (n = 18, 22.5 ± 1 months of age). Data were submitted to principal component analysis (PCA), analysis of variance (ANOVA), enrichment analysis, and Pearson's correlation analysis. The phenotypes did not show differences between treatments (p > 0.05). Metabolites PCA showed an overlap of treatment clusters in the analysis. We found significant metabolites in ANOVA (p ≤ 0.05; Glycine, Hydroxytetradecadienylcarnitine, Aminoadipic acid and Carnosine). Enrichment analysis revealed some biological processes (Histidine metabolism, beta-Alanine metabolism, and Lysine degradation). Pearson's correlation analysis showed 29 significant correlated metabolites with BW and 1 metabolite correlated with LW. In summary, prenatal nutrition did not show effects on the phenotypes evaluated, but affected some metabolites and biological pathways, mainly related to oxidative metabolism. In addition, BW seems to influence the hepatic metabolome more than LW, due to the amount and magnitude of correlations found.