Prenatal and Postnatal Nutrition Influence Pancreatic and Intestinal Carbohydrase Activities of Ruminants

In ruminant livestock species, nutrition can play an important role in the long-term programming of gastrointestinal function. Pancreatic and small intestinal digestive enzymes are important for postruminal digestion of carbohydrates and protein. Carbohydrases have been shown to respond to changes in the level of feed intake and the dietary inclusion of specific nutrients, including arginine, butyrate, folic acid, fructose, and leucine. Understanding how diet influences enzyme development and activity during prenatal and postnatal life could lead to the development of dietary strategies to optimize offspring growth and development to increase digestive efficiency of ruminant livestock species. More research is needed to understand how changes in fetal or neonatal carbohydrase activities in response to nutrition influence long-term growth performance and efficiency in ruminant livestock species to optimize nutritional strategies

Nutritional and Physiological Constraints Contributing to Limitations in Small Intestinal Starch Digestion and Glucose Absorption in Ruminants

Increased efficiency of nutrient utilization can potentially be gained with increased starch digestion in the small intestine in ruminants. However, ruminants have quantitative limits in the extent of starch disappearance in the small intestine. The objective is to explore the nutritional and physiological constraints that contribute to limitations of carbohydrate assimilation in the ruminant small intestine. Altered digesta composition and passage rate in the small intestine, insufficient pancreatic α-amylase and/or small intestinal carbohydrase activity, and reduced glucose absorption could all be potentially limiting factors of intestinal starch assimilation. The absence of intestinal sucrase activity in ruminants may be related to quantitative limits in small intestinal starch hydrolysis. Multiple sequence alignment of the sucrase-isomaltase complex gives insight into potential molecular mechanisms that may be associated with the absence of intestinal sucrase activity, reduced capacity for intestinal starch digestion, and limitations in the efficiency of feed utilization in cattle and sheep. Future research efforts in these areas will aid in our understanding of small intestinal starch digestion and glucose absorption to optimize feeding strategies for increased meat and milk production efficiency

Interaction of replacing corn silage with soyhulls as a roughage source with or without 3% added wheat straw in the diet: impacts on intake, digestibility, and ruminal fermentation in steers fed high-concentrate diets

Six ruminally cannulated steers [475.0 ± 49.6 kg initial body weight (BW)] were used in a 6 × 3 incomplete Latin square design (six treatments and three periods), to evaluate the impacts replacing of corn silage with pelleted soyhulls as roughage in high-concentrate finishing diets containing 30% modified distillers grains with solubles. Treatments were based on increasing dietary inclusion of soyhulls and consisted of: (1) Control (0), roughage supplied by dietary inclusion of 20% corn silage [dry matter (DM) basis]; (2) 50% replacement of corn silage with soyhulls (50); (3) 100% replacement of corn silage with soyhulls (100), and the same three treatments repeated with 3% added wheat straw (DM basis) replacing corn in the diet (0S, 50S, and 100S, respectively). Absolute dry matter intake (DMI; kg/d basis) tended to decrease both linearly and quadratically (P ≤ 0.09) and proportional DMI (% of BW) decreased linearly (P = 0.04) with increasing soyhull inclusion but was not affected by the addition of straw in the diet (P = 0.68). Total tract digestibility of organic matter and crude protein were not affected by soyhull inclusion or added straw (P ≥ 0.32). Ruminal pH did not differ (P = 0.65) with increasing soyhull inclusion but increased with the addition of straw (P \u3c 0.01; 5.9 vs. 6.1 for no straw and straw, respectively). Molar proportions of acetate and butyrate decreased while propionate increased with increased soyhull inclusion (P ≤ 0.03; linearly and quadratically, respectively). Ruminal fluid kinetics were unaffected by either rate of replacement of corn silage with soyhulls or wheat straw inclusion (P ≥ 0.13). Decreases in DMI observed in this study would likely decrease finishing cattle performance and underscores the need for additional research before recommending this practice to cattle feeders

Shrub Communities, Spatial Patterns, and Shrub-Mediated Tree Mortality following Reintroduced Fire in Yosemite National Park, California, USA

Shrubs contribute to the forest fuel load; their distribution is important to tree mortality and regeneration, and vertebrate occupancy. We used a method new to fire ecology—extensive continuous mapping of trees and shrub patches within a single large (25.6 ha) study site—to identify changes in shrub area, biomass, and spatial pattern due to fire reintroduction by a backfire following a century of fire exclusion in lower montane forests of the Sierra Nevada, California, USA. We examined whether trees in close proximity to shrubs prior to fire experienced higher mortality rates than trees in areas without shrubs. We calculated shrub biomass using demography subplots and existing allometric equations, and we developed new equations for beaked hazel (Corylus cornuta ssp. californica [A. de Candolle] E. Murray) from full dissection of 50 stems. Fire decreased shrub patch area from 15.1 % to 0.9 %, reduced live shrub biomass from 3.49 Mg ha−1 to 0.27 Mg ha−1, and consumed 4.41 Mg ha−1 of living and dead shrubs. Distinct (non-overlapping) shrub patches decreased from 47 ha−1 to 6 ha−1. The mean distance between shrub patches increased 135 %. Distances between montane chaparral patches increased 285 %, compared to a 54 % increase in distances between riparian shrub patches and an increase of 267 % between generalist shrub patches. Fire-related tree mortality within shrub patches was marginally lower (67.6 % versus 71.8 %), showing a contrasting effect of shrubs on tree mortality between this forest ecosystem and chaparral-dominated ecosystems in which most trees are killed by fire

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Whole-body microbiota of newborn calves and their response to prenatal vitamin and mineral supplementation

Early life microbial colonization and factors affecting colonization patterns are gaining interest due to recent developments suggesting that early life microbiome may play a role in Developmental Origins of Health and Disease. In cattle, limited information exists on the early microbial colonization of anatomical sites involved in bovine health beyond the gastrointestinal tract. Here, we investigated 1) the initial microbial colonization of seven different anatomical locations in newborn calves and 2) whether these early life microbial communities and 3) serum cytokine profiles are influenced by prenatal vitamin and mineral (VTM) supplementation. Samples were collected from the hoof, liver, lung, nasal cavity, eye, rumen (tissue and fluid), and vagina of beef calves that were born from dams that either received or did not receive VTM supplementation throughout gestation (n = 7/group). Calves were separated from dams immediately after birth and fed commercial colostrum and milk replacer until euthanasia at 30 h post-initial colostrum feeding. The microbiota of all samples was assessed using 16S rRNA gene sequencing and qPCR. Calf serum was subjected to multiplex quantification of 15 bovine cytokines and chemokines. Our results indicated that the hoof, eye, liver, lung, nasal cavity, and vagina of newborn calves were colonized by site-specific microbiota, whose community structure differed from the ruminal-associated communities (0.64 ≥ R2 ≥ 0.12, p ≤ 0.003). The ruminal fluid microbial community was the only one that differed by treatment (p < 0.01). However, differences (p < 0.05) by treatment were detected in microbial richness (vagina); diversity (ruminal tissue, fluid, and eye); composition at the phylum and genus level (ruminal tissue, fluid, and vagina); and in total bacterial abundance (eye and vagina). From serum cytokines evaluated, concentration of chemokine IP-10 was greater (p = 0.02) in VTM calves compared to control calves. Overall, our results suggest that upon birth, the whole-body of newborn calves are colonized by relatively rich, diverse, and site-specific bacterial communities. Noticeable differences were observed in ruminal, vaginal, and ocular microbiota of newborn calves in response to prenatal VTM supplementation. These findings can derive future hypotheses regarding the initial microbial colonization of different body sites, and on maternal micronutrient consumption as a factor that may influence early life microbial colonization

Patient Discomfort Associated with the Use of Intra-arterial Iodinated Contrast Media: A Meta-Analysis of Comparative Randomized Controlled Trials

<p>Abstract</p> <p>Background</p> <p>Discomfort characterized by pain and warmth are common adverse effects associated with the use of intra-arterial iodinated contrast media (CM). The objective of this review was to pool patient-reported outcomes available from head-to-head randomized controlled trials (RCTs) and to compare the discomfort rates associated with iso-osmolar contrast media (IOCM; i.e., iodixanol) to those reported with various low-osmolar contrast media (LOCM).</p> <p>Methods</p> <p>A review of the literature published between 1990 and 2009 available through Medline, Medline Preprints, Embase, Biological Abstracts, BioBase, Cab Abstracts, International Pharmaceutical Abstracts, Life Sciences Collection, Inside Conferences, Energy Database, Engineering Index and Technology Collection was performed to compare rates of discomfort associated with the use of the IOCM (iodixanol) vs. various LOCM agents in head-to-head RCTs. All trials with a Jadad score ≥2 that reported patient discomfort data following intra-arterial administration of CM were reviewed, coded, and extracted.</p> <p>Results</p> <p>A total of 22 RCTs (n = 8087) were included. Overall discomfort (regardless of severity) was significantly different between patients receiving IOCM and various LOCMs (risk difference [RD] -0.049; 95% confidence interval [CI]: -0.076, -0.021; p = 0.001). IOCM was favored over all LOCMs combined with a summary RD value of -0.188 (95% CI: -0.265, -0.112; p < 0.001) for incidence of pain, regardless of severity. A greater reduction in the magnitude of pain was observed with IOCM (iodixanol), particularly with selective limb and carotid/intracerebral procedures. Similarly, the meta-analysis of warmth sensation, regardless of severity, favored IOCM over LOCMs with an RD of -0.043 (95% CI: -0.074, -0.011; p = 0.008). A positive linear relationship was observed between the discomfort effect size and age and a negative relationship with increasing proportion of women. The opposite trends were observed with warmth sensation.</p> <p>Conclusions</p> <p>IOCM was associated with less frequent and severe patient discomfort during intra-arterial administration. These data support differences in osmolality as a possible determinant of CM discomfort.</p

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin