Ruminal fermentation pattern of acidosis-induced cows fed either monensin or polyclonal antibodies preparation against several ruminal bacteria

This study was designed to evaluate a spray-dried multivalent polyclonal antibody preparation (PAP) against lactate-producing bacteria as an alternative to monensin (MON) to control ruminal acidification. Holstein cows (677 ± 98 kg) fitted with ruminal cannulas were allocated in an incomplete Latin square design with two 20 days period. Cows were randomly assigned to control (CTL), PAP, or MON treatments. For each period, cows were fed a forage diet in the first 5 days (d−5 to d−1), composed of sugarcane, urea and a mineral supplement, followed by a 74% concentrate diet for 15 days (d 0 to d 14). There were no treatment main effects (P > 0.05) on dry matter intake (DMI) and microbial protein synthesis. However, there was a large peak (P < 0.01) of intake on d 0 (18.29 kg), followed by a large decline on d 1 (3.67 kg). From d2, DMI showed an increasing pattern (8.34 kg) and stabilized around d 8 (12.96 kg). Higher mean pH was measured (P < 0.01) in cattle-fed MON (6.06 vs. PAP = 5.89 and CTL = 5.91). The ruminal NH3-N concentration of CTL-fed cows was lower (P < 0.01) compared to those fed MON or PAP. The molar concentration of acetate and lactate was not affected (P > 0.23) by treatments, but feeding MON increased (P = 0.01) propionate during the first 4 days after the challenge. Feeding MON and PAP reduced (P = 0.01) the molar proportion of butyrate. MON was effective in controlling pH and improved ruminal fermentation of acidosis-induced cows. However, PAP was not effective in controlling acidosis. The acidosis induced by the challenge was caused by the accumulation of SCFAs. Therefore, the real conditions for evaluation of this feed additive were not reached in this experiment, since this PAP was proposed to work against lactate-producing bacteria

Microcephaly, sensorineural deafness and Currarino triad with duplication–deletion of distal 7q

Currarino syndrome (CS) is a peculiar form of caudal regression syndrome [also known as autosomal dominant sacral agenesis (OMIM no. 176450)] characterised by (1) partial absence of the sacrum with intact first sacral vertebra, (2) a pre-sacral mass and (3) anorectal anomalies (Currarino triad). We studied a 3-year-old girl with Currarino triad who had additional systemic features and performed array comparative genomic hybridisation to look for chromosomal abnormalities. This girl had the typical spectrum of anomalies of the CS including (a) partial sacral agenesis (hemisacrum with remnants of only sacral S1–S2 vertebrae and a residual S3 vertebral body) associated with complete coccygeal agenesis, (b) pre-intrasacral dermoid, (c) intra-dural lipoma, (d) ectopic anus and (e) tethered cord. She had, in addition, pre- and post-natal growth impairment (<3rd percentile), severe microcephaly (<−3 SD) with normal gyration pattern and lack of cortical thickening associated with a hypoplastic inferior vermis, facial dysmorphism, sensorineural deafness and decreased serum levels of IGF-1. A de novo 10.3-Mb duplication of 7q34–q35 and an 8.8-Mb deletion on 7q36 were identified in this patient. The Homeobox HLXB9 (CS) gene is contained within the deletion accounting for the CS phenotype including microcephaly. The spectrums of associated abnormalities in the IGF-1 deficiency growth retardation with sensorineural deafness and mental retardation syndrome (OMIM no. 608747) are discussed. To the best of our knowledge, this is the first reported case of a patient with distal 7q chromosomal imbalance and features of CS triad (including microcephaly) and the first documented case of a patient with normal gyration pattern microcephaly. The spectrum of associated anomalies in this newly recognised phenotype complex consists of growth failure, typical facial anomalies with additional (previously unreported) nervous system abnormalities (e.g. sensorineural deafness) and somatomedin C deficiency

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Adoption of adaptation protocols and feed additives to improve performance of feedlot cattle

ABSTRACTThe evolution of ruminants was largely influenced by the symbiotic relationship between ruminal microbiota and the host. Within the rumen, these microorganisms degrade feedstuffs to produce organic acids and synthesize microbial protein, as energy and protein source for ruminants, respectively. This process is accelerated when these animals are transferred to feedlot diets. This review brings the most current studies that reported the most used nutritional managements in this transition process, in order to avoid metabolic disturbances, in which rumen development is a fundamental point. Also, this review brings the main biomolecules used as feed additive, which can in the help control of fermentation processes in order to minimize energetically inefficient processes within the rumen, as well as losses by excretion to the environment, which are widely questioned by be environmental pollutants. Furthermore, the main results of research on animal performance in response to these additives are reported, supplemented alone or associated with different feed additives when used on diets with high grain contents, as well as evaluating the potential of additives as antibiotics alternatives, a fact that has been discussed and is worrying since the use of ionophores or non-ionophores antibiotics represent practically the totality of feedlot diets

Effects of adding a spray-dried polyclonal antibody preparation on ruminal fermentation patterns and digestibility of cows fed high concentrate diets

The present study aimed to evaluate the effects of different doses of a spray-dried polyclonal antibody preparation against specific ruminal bacteria on rumen fermentation parameters as well as protozoa counts, in situ degradability of sugarcane neutral detergent fibre (NDF) and total tract apparent digestibility of total diet in cows fed high concentrate diets. Eight ruminally-cannulated cows were used in a replicated 4 4 Latin square design with four experimental periods of 21 days. The treatments were: T1 (control), 0.0 g/d of multivalent polyclonal antibody preparation (PAP-MV); T2, 1.5 g/d of PAP-MV; T3, 3.0 g/d of PAP-MV; T4, 4.5 g/d of PAP-MV. Sample collection for rumen fermentation parameters was carried out the last day of each period at 0, 2, 4, 6, 8, 10 and 12 h after morning meal. For protozoa counts, samples were collected the last day of each period at 0 and 4 h after feeding. In situ degradability of sugarcane NDF was performed the last 5 days of each period, while total tract apparent digestibility of total diet was assessed the last 10 days of each period. Regardless of sampling time, there was no linear or quadratic effect on rumen pH, total concentration of short chain fatty acids, molar proportion of acetate, propionate and butyrate, ammonia nitrogen (NH3-N) or lactate. No treatment effects were detected for protozoa counts, in situ degradability of sugarcane NDF and total tract apparent digestibility of total diet. In conclusion, different levels of spray-dried PAP-MV were not sufficient to alter rumen environment.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Relationships of the Microbial Communities with Rumen Epithelium Development of Nellore Cattle Finished in Feedlot Differing in Phenotypic Residual Feed Intake

The objective of this study was to examine the relationships among ruminal microbial community, rumen morphometrics, feeding behavior, feedlot performance, and carcass characteristics of Nellore cattle, classified by residual feed intake (RFI). Twenty-seven Nellore yearling bulls with an initial body weight (BW) of 423.84 &plusmn; 21.81 kg were fed in feedlot for 107 d in individual pens to determine the RFI phenotype. Bulls were categorized as high RFI (&gt;0.5 SD above the mean, n = 8), medium RFI (&plusmn;0.5 SD from the mean, n = 9), and low RFI (&lt;0.5 SD below the mean, n = 10). At harvest, whole rumen content samples were collected from each bull to evaluate ruminal microbial community, including bacteria and protozoa. The carcass characteristics were determined by ultrasonography at the beginning and at the end of the experimental period, and behavior data were collected on d 88. As a result of ranking Nellore bulls by RFI, cattle from low-RFI group presented lesser daily dry matter intake (DMI), either in kilograms (p &lt; 0.01) or as percentage of BW (p &lt; 0.01) than high-RFI yearling bulls, resulting in improved gain:feed (G:F). However, variables, such as average daily gain (ADG), final BW, hot carcass weight (HCW) and other carcass characteristics did not differ (p &gt; 0.05) across RFI groups. The eating rate of either dry matter (DM )(p = 0.04) or neutral detergent fiber (NDF) (p &lt; 0.01) was slower in medium-RFI yearling bulls. For ruminal morphometrics an RFI effect was observed only on keratinized layer thickness, in which a thinner layer (p = 0.04) was observed in low-RFI Nellore yearling bulls. Likewise, Nellore yearling bulls classified by the RFI did not differ in terms of Shannon&rsquo;s diversity (p = 0.57) and Chao richness (p = 0.98). Our results suggest that the differences in feed efficiency of Nellore bulls differing in phenotypic RFI should be attributed to metabolic variables other than ruminal microorganisms and epithelium, and deserves further investigation

Relationships of the Microbial Communities with Rumen Epithelium Development of Nellore Cattle Finished in Feedlot Differing in Phenotypic Residual Feed Intake

The objective of this study was to examine the relationships among ruminal microbial community, rumen morphometrics, feeding behavior, feedlot performance, and carcass characteristics of Nellore cattle, classified by residual feed intake (RFI). Twenty-seven Nellore yearling bulls with an initial body weight (BW) of 423.84 ± 21.81 kg were fed in feedlot for 107 d in individual pens to determine the RFI phenotype. Bulls were categorized as high RFI (>0.5 SD above the mean, n = 8), medium RFI (±0.5 SD from the mean, n = 9), and low RFI (n = 10). At harvest, whole rumen content samples were collected from each bull to evaluate ruminal microbial community, including bacteria and protozoa. The carcass characteristics were determined by ultrasonography at the beginning and at the end of the experimental period, and behavior data were collected on d 88. As a result of ranking Nellore bulls by RFI, cattle from low-RFI group presented lesser daily dry matter intake (DMI), either in kilograms (p p p > 0.05) across RFI groups. The eating rate of either dry matter (DM )(p = 0.04) or neutral detergent fiber (NDF) (p p = 0.04) was observed in low-RFI Nellore yearling bulls. Likewise, Nellore yearling bulls classified by the RFI did not differ in terms of Shannon’s diversity (p = 0.57) and Chao richness (p = 0.98). Our results suggest that the differences in feed efficiency of Nellore bulls differing in phenotypic RFI should be attributed to metabolic variables other than ruminal microorganisms and epithelium, and deserves further investigation

Influence of nutritional management prior to adaptation to a feedlot diet on ruminal microbiota of Nellore cattle

The objective of this study was to evaluate the effect of either a limited forage intake or concentrate supplementation prior to the adaptation to high-concentrate diets on dry matter intake, ruminal pH, bacteria, and protozoa of Nellore cattle. The experiment was designed as a two 3×3 Latin square, and six cannulated Nellore steers were used. Each experimental period was composed by three feeding phases: pre-adaptation (14 days), adaptation (12 days), and finishing (seven days) diet, in a total of 33 days per period. The steers were assigned to one of three pre-adaptation dietary treatments: control (Tifton hay fed ad libitum + mineral supplement), restriction (Tifton hay fed at 1.4% of BW + mineral supplement), and concentrate (Tifton hay fed ad libitum + 0.5% of BW of a mix of concentrate feedstuffs and mineral supplement). The adaptation period consisted of two adaptation diets, which contained 72 and 79% concentrate for six days each. The finishing diet contained 86% concentrate. During the pre-adaptation phase, restricted cattle had higher pH than concentrate-fed cattle. There was a reduction in M. elsdenii relative population in cattle from either restriction or concentrate groups. During adaptation and finishing phases, cattle from concentrate group had smaller F. succinogenes populations compared with the control group. The previous nutritional backgrounds impact ruminal microbiota during adaptation and finishing phases without causing any negative effect on ruminal pH. Feeding concentrate prior to the adaptation positively impacted the transition to high-concentrate diets and promoted increased dry matter intak