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Gut microbial enzymes, bile salt hydrolases (BSHs) are the gateway enzymes for bile acid (BA) modification in the gut. This activity is a promising target for developing innovative non-antibiotic growth promoters to enhance animal production and health. Compelling evidence has shown that inhibition of BSH activity should enhance weight gain by altering the BA pool, host signalling and lipid metabolism. We recently identified a panel of promising BSH inhibitors. Here, we address the potential of them as alternative, effective, non-antibiotic feed additives, for commercial application, to promote animal growth using a chicken model. In this study, the in vivo efficacy of three BSH inhibitors (caffeic acid phenethylester, riboflavin, carnosic acid) were evaluated. 7-day old chicks (10 birds/group) were either untreated or they received one of the specific BSH inhibitors (25 mg/kg body weight) via oral gavage for 17 days. The chicks in treatment groups consistently displayed higher body weight gain than the untreated chicks. Metabolomic analysis demonstrated that BSH inhibitor treatment led to significant changes in both circulating and intestinal BA signatures in support of blunted intestinal BSH activity. Consistent with this finding, liver and intestinal tissue RNA-Seq analysis showed that carnosic acid treatment significantly altered expression of genes involved in lipid and bile acid metabolism. Taken together, this study validates microbial BSH activity inhibition as an alternative target and strategy to antibiotic treatment for animal growth promotion.

Dietary omega-3 polyunsaturated fatty acids (n-3 PUFA) are precursors for lipid metabolites that reduce inflammation. Two experiments were conducted to test the hypothesis that enriching the sow diet in n-3 PUFA during late gestation and throughout lactation reduces stress and inflammation and promotes growth in weaned pigs. A protected fish oil product (PFO; Gromega) was used to enrich the diet in n-3 PUFA. In the initial experiment, time-bred gilts were fed a gestation and lactation diet supplemented with 0% (control; n = 5), 0.25% (n = 4), 0.5% (n = 4), or 1% (n = 5) PFO from 101 ± 2 d of gestation to day 16 of lactation. Adding 1% PFO to the diet increased the n-3:n-6 PUFA ratio in colostrum and milk compared with controls (P = 0.05). A subsequent experiment was performed to determine whether supplementing the sow diet with 1% PFO improved growth and reduced circulating markers of acute inflammation and stress in the offspring. Plasma was harvested from piglets (16 per treatment group) on day 0 (d of weaning) and days 1 and 3 postweaning. Pigs from the 1% PFO treatment group weighed more (P = 0.03) on day 3 postweaning and had a greater (P ˂ 0.05) n-3:n-6 PUFA ratio in plasma on each day sampled compared with 0% PFO controls. There was an overall treatment effect on plasma total cortisol (P = 0.03) and haptoglobin (P = 0.04), with lesser concentrations in pigs on the 1% PFO diet. Plasma corticosteroid-binding globulin (CBG) concentrations were not different between treatment groups but were less (P ˂ 0.001) on days 1 and 3 when compared with day 0. The resultant free cortisol index [FCI (cortisol/CBG)] was less (P = 0.02) on days 1 and 3 for pigs from the 1% treatment group compared with the controls. An ex vivo lipopolysaccharide (LPS) challenge of whole blood collected on days 0 and 1 was used to determine whether 1% PFO attenuated release of inflammatory cytokines (IL-1β, IL-6, and TNF-α). Blood from pigs within the 1% PFO treatment group tended (P = 0.098) to have a lesser mean concentration of TNF-α in response to LPS compared with blood from controls. These results suggest that providing a PFO supplement as 1% of the diet to sows beginning in late gestation and during lactation can increase the n-3:n-6 PUFA ratio in their offspring, which may improve growth and reduce the acute physiological stress response in the pigs postweaning., (Published by Oxford University Press on behalf of the American Society of Animal Science 2019.)

Human activity has extensively transformed the land surface by agricultural intensification and urbanization. In soil, nematodes are the most abundant invertebrates. The effect of human interventions was assessed on overall richness, overall abundance, richness and abundance of nematodes of each trophic group and colonizer-persister (c-p) guild by comparing urban, agriculture and disturbed grassland (DGL) with natural grassland (NGL) and forest ecosystems. Meta-analyses were conducted to generate quantitative summaries from 111 published articles that met the inclusion criteria, 91 expressed data in grams and 20 expressed data in cm 3 . Results from data expressed per 100 g of soil indicated that overall richness was higher in forest than in NGL, DGL, urban, and agriculture ecosystems. The richness of all c-p guilds and of all trophic groups except herbivores was highest in forest ecosystems. In contrast, overall abundance was highest in DGL, agriculture and forest ecosystems. The abundance of c-p 1, c-p 2 and c-p 3 guilds and bacterivores, fungivores and herbivores was highest in disturbed ecosystems, while the abundance of c-p 4 and c-p 5 guilds and predators and omnivores was highest in relatively undisturbed ecosystems. Results from data expressed as nematodes per 100 cm 3 of soil indicated that abundance followed a similar pattern, but richness often differed between the two methodologies. These meta-analyses strengthen the concept that human interventions adversely impact both richness and abundance using nematodes as soil health bioindicators., Human activity has extensively transformed the land surface by agricultural intensification and urbanization. In soil, nematodes are the most abundant invertebrates. The effect of human interventions was assessed on overall richness, overall abundance, richness and abundance of nematodes of each trophic group and colonizer-persister (c-p) guild by comparing urban, agriculture and disturbed grassland (DGL) with natural grassland (NGL) and forest ecosystems. Meta-analyses were conducted to generate quantitative summaries from 111 published articles that met the inclusion criteria, 91 expressed data in grams and 20 expressed data in cm 3 . Results from data expressed per 100 g of soil indicated that overall richness was higher in forest than in NGL, DGL, urban, and agriculture ecosystems. The richness of all c-p guilds and of all trophic groups except herbivores was highest in forest ecosystems. In contrast, overall abundance was highest in DGL, agriculture and forest ecosystems. The abundance of c-p 1, c-p 2 and c-p 3 guilds and bacterivores, fungivores and herbivores was highest in disturbed ecosystems, while the abundance of c-p 4 and c-p 5 guilds and predators and omnivores was highest in relatively undisturbed ecosystems. Results from data expressed as nematodes per 100 cm 3 of soil indicated that abundance followed a similar pattern, but richness often differed between the two methodologies. These meta-analyses strengthen the concept that human interventions adversely impact both richness and abundance using nematodes as soil health bioindicators.

Hyperthermia occurring 10-12 h after LH surge reduces quality of maturing oocyte, thereby reducing fertility. Objective was to examine consequences of an acute heat stress and the influence of certain hormones on the thermoregulatory responses of lactating cows during this critical period. Between the months of February through May, cows were transported to a facility and maintained at a temperature-humidity index (THI) of 65.9 ± 0.2 (thermoneutral) or exposed to changes in THI to simulate what may occur during an acute heat stress event (71-86 THI; heat stress); cows were rapidly cooled thereafter. Mixed model regressions with repeated measures were used to test respiration rates (RR) and rectal temperature (RT). Within 40 and 110 min of increasing THI, RR increased in a quadratic fashion (P < 0.001); RT increased by 0.04 ± 0.1 °C (P < 0.001) per unit THI. Changes in RR lagged THI and preceded rises in RT. Average THI 3-days before treatment (prior THI) influenced RR (P = 0.050) and RT (P < 0.001) changes. Increased RR was more noticeable in heat-stressed cows when prior THI was in the 40 s. Rectal temperature of heat-stressed cows was 0.8 ± 0.02 °C lower when prior THI was in the 40 s versus low 60 s. Levels of progesterone and luteinizing hormone before treatment were predictive of thermoregulatory response in heat-stressed cows. Rapid cooling decreased RR by 0.6 ± 0.1 bpm (P < 0.001) and RT by 0.02 ± 0.002 °C per min (P < 0.002). Speed and magnitude of thermoregulatory changes to an acute heat stress and after sudden cooling emphasizes importance of strategic cooling before ovulation. Efforts to do so when prior THI approaches levels expected to induce mild stress are especially important. Respiration rate is a useful indicator of the degree of hyperthermia a lactating cow is experiencing., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The use of embryo transfer (ET) in cattle is important for profitability and improved genetic gains. The advent of the commercial embryo collection and transfer industry has led to advancements in multiple techniques and practices. Specific variables, however, have historically affected pregnancy rates but an understanding of the magnitude of these effects in the current industry is limited. Transfer location (cranial, middle, or caudal third of the uterine horn ipsilateral to the ovary with a CL), transfer score (range of 1-3 with 1 being excellent and 3 poor, based on difficulty of accessing the site of embryo deposition), and amount of time to complete a transfer, therefore, were recorded. These variables were collected in a setting designed to mimic commercial production practices as well as exaggerated time (due to data collection) to assess effects on pregnancy rates. Fresh and frozen in vivo-derived embryos (n = 256) from Bos taurus cows were transferred to Bos taurus recipients. There tended to be more pregnancies when embryos were deposited in the cranial part of the uterus (P =  0.08) compared to the middle and caudal third of the uterus. With a lesser degree of difficulty in transfers (score 1), there tended to be more pregnancies established (P =  0.07). When lesser time was needed for transferring embryos and collecting data, there were greater pregnancy rates (P =  0.03). Thus, these traditionally accepted variables of influence (site of embryo placement in uterus, difficulty, and time) continue to influence ET pregnancy success., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Chloroplast DNA is a part of plant non-nuclear genome, and is of particular interest for lineage studies. Moreover, the non-coding regions of cpDNA display higher mutation rates than the conserved coding cpDNA, which has been employed for phylogenetic and population research. We analyzed the cpDNA of 332 gDNA samples from collections of Cornus florida and C. kousa (commercial cultivars, breeding selections, and wild kousa accessions from Asia), using the chlorotyping system developed on North America-native, wild accessions of C. florida. Our results indicated significant differences in chlorotype frequencies between the two species. Cornus florida samples were represented by all major chlorotypes previously described, whereas all C. kousa samples analyzed had only one of the chlorotype patterns shown by C. florida. The chlorotyping analytic panel was then expanded by sequencing the targeted three non-coding cpDNA regions. Results indicated a major difference in the maternally-inherited cpDNA between the two closely related Big-Bracted Cornus species. Chlorotype diversity and differences in the proportion of informative sites in the cpDNA regions of focus emphasized the importance of proper loci choice for cpDNA-based comparative studies between the closely related dogwood species. Phylogenetic analyses of the retrieved sequences for the other species of Cornus provided information on the relative utility of the cpDNA regions studied and helped delineate the groups (Big-Bracted, Cornelian Cherries, Blue/White-Fruited) within the genus. Genealogical relationships based on the cpDNA sequences and the inferred chlorotype networks indicated the need for continued analyses across further non-coding cpDNA regions to improve the phylogenetic resolution of dogwoods., Competing Interests: The authors have declared that no competing interests exist.

The intimate association of cumulus cells with one another and with the oocyte is important for regulating oocyte meiotic arrest and resumption. The objective of this study was to determine the effects of heat stress on cumulus cell communication and functions that may be related to accelerated oocyte meiosis during early maturation. Bovine cumulus-oocyte complexes underwent in vitro maturation for up to 6 h at thermoneutral control (38.5°C) or elevated (40.0, 41.0 or 42.0°C) temperatures. Gap junction communication between the cumulus cells and the oocyte was assessed using the fluorescent dye calcein after 4 h of in vitro maturation. Dye transfer was reduced in cumulus-oocyte complexes matured at 41.0°C or 42.0°C; transfer at 40.0°C was similar to control (P < 0.0001). Subsequent staining of oocytes with Hoechst revealed that oocytes matured at 41.0 or 42.0°C contained chromatin at more advanced stages of condensation. Maturation of cumulus-oocyte complexes at elevated temperatures reduced levels of active 5' adenosine monophosphate activated kinase (P = 0.03). Heat stress exposure had no effect on active extracellular-regulated kinase 1/2 in oocytes (P = 0.67), associated cumulus cells (P = 0.60) or intact cumulus-oocyte complexes (P = 0.44). Heat-induced increases in progesterone production by cumulus-oocyte complexes were detected during the first 6 h of maturation (P = 0.001). Heat-induced alterations in gap junction communication and other cumulus-cell functions likely cooperate to accelerate bovine oocyte meiotic progression.

The objective of this study was to evaluate relationships between measurements of temperature-humidity index (THI) and rectal, vaginal, and udder surface temperatures in lactating cows exposed to heat stress (HS). In experiment 1, 12 multiparous and 8 primiparous Holstein cows experienced a THI ranging from 69 to 76 at 2000 to 1000 h and THI from 74 to 82 at 1000 to 2000 h (peaked at 82 from 1400 to 1800 h). Cows were exposed to HS 10 h daily for 21 d. Measurements of rectal temperature (RT) and udder surface temperature were collected at 1000 and 1500 h (±30 min). Vaginal temperature was monitored every 10 min using digital loggers, averaged over 1 h, and paired with corresponding rectal and udder surface temperature data. In experiment 2, 12 multiparous Holstein cows experienced a THI ranging from 60 to 76 at 2000 to 1000 h and THI from 69 to 83 at 1000 to 2000 h (peaked at 83 from 1600 and 1900 h), eliciting 10 h/d of HS for 7 d. Rectal and udder surface temperatures were analyzed at 0700 and 1500 h (±30 min). Vaginal temperature was recorded and analyzed as indicated in experiment 1. Afternoon THI showed weak correlations with surface temperature (r = 0.19, n = 420 in experiment 1; r = 0.23, n = 84 in experiment 2), weak to moderate correlations with RT (r = 0.34, n = 366 in experiment 1; r = 0.26, n = 84 in experiment 2), and moderate correlations with vaginal temperature (r = 0.34, n = 175 in experiment 1; r = 0.35, n = 40 in experiment 2). Moreover, vaginal temperature increased 0.10 and 0.22°C per unit of THI (R 2 = 0.15 in experiment 1; R 2 = 0.40 in experiment 2). Afternoon vaginal temperature strongly correlated with RT (r = 0.69, n = 131 in experiment 1; r = 0.63, n = 37 in experiment 2) and explained 57 (experiment 1) and 68% (experiment 2) of variation in RT. Surface temperature showed moderate to strong correlations with RT (r = 0.57, n = 84) and vaginal temperature (r = 0.74, n = 37) in experiment 2. In conclusion, THI showed a weak to moderate relationship with core body temperatures and explained the increase in rectal and vaginal temperatures experienced by HS cows. Compared with rectal temperature, vaginal temperature showed stronger relationships with THI and can be used to determine thermal load. Udder surface temperature showed a moderate to strong relationship with core body temperature, and this relationship may support the use of surface temperature data to manage thermal load in HS cows., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Hyperthermia during estrus has direct consequences on the maturing oocyte that carries over to the resultant embryo to compromise its ability to continue in development. Because early embryonic development is reliant upon maternal transcripts and other ooplasmic components, we examined impact of heat stress on bovine oocyte transcripts using microarray. Oocytes were matured at 38.5ºC for 24 h or 41.0ºC for the first 12 h of in vitro maturation; 38.5ºC thereafter. Transcriptome profile was performed on total (adenylated + deadenylated) RNA and polyadenylated mRNA populations. Heat stress exposure altered the abundance of several transcripts important for mitochondrial function. The extent to which transcript differences are coincident with functional changes was evaluated by examining reactive oxygen species, ATP content, and glutathione levels. Mitochondrial reactive oxygen species levels were increased by 6 h exposure to 41.0ºC while cytoplasmic levels were reduced compared to controls (P < 0.0001). Exposure to 41.0ºC for 12 h increased total and reduced glutathione levels in oocytes at 12 h but reduced them by 24 h (time × temperature P < 0.001). ATP content was higher in heat-stressed oocytes at 24 h (P < 0.0001). Heat-induced increases in ATP content of matured oocytes persisted in early cleavage-stage embryos (8- to 16-cell embryos; P < 0.05) but were no longer apparent in blastocysts (P > 0.05). Collectively, results indicate that direct exposure of maturing oocytes to heat stress may alter oocyte mitochondrial processes/function, which is inherited by the early embryo after fertilization.

Widely used as an antimicrobial in antibacterial bar soaps, triclocarban (3,4,4'-trichlorocarbanilide; TCC) is effective against Gram-positive bacteria but shows little efficacy against Gram-negative strains, potentially altering the composition of indigenous microflora within and on the human body. To date, the consequence of continuous or previous nonprescription antimicrobial exposure from compounds in personal care products on commensal microflora is still elusive. Previous research has shown that TCC exposure during gestation and lactation induced dysbiosis of gut microbial communities among exposed dams and neonates. However, the impact of antimicrobial exposure specifically after discontinuation of the use of TCC on the gut microbiota has not been investigated. In this study, weaned Sprague Dawley rats (postnatal day, PND 22) were provided ad lib access to TCC-supplemented diet (0.2% w/w or 0.5% w/w) for 4 weeks (phase I) followed by a 4-week washout period (phase II) to determine gut microflora changes both during continuous exposure to TCC and to determine the potential rebound following TCC withdrawal. Fecal samples were collected at baseline (PND 22) prior to TCC exposure and throughout phase I and phase II. The V4 region of 16S rDNA was sequenced from extracted total fecal DNA with the MiSeq platform. Exposure to both 0.2% w/w and 0.5% w/w TCC was sufficient to alter diversity of microbiota during phase I of treatment. This effect was further prolonged into phase II, even when TCC exposure was discontinued. Collectively, these data highlight the impact of both continuous and prior TCC exposure on gut microbial ecology and shed light onto the potential long-term health risk of daily nonprescription antimicrobial personal care product use.

In spite of the increasing prevalence of Streptococcus uberis mastitis, its pathogenesis and associated virulence factors are not clearly defined. The aim of this study was to identify virulence associated genes and their products that can be used to develop effective vaccine to control bovine S. uberis mastitis. S. uberis was co-cultured with primary bovine mammary epithelial cells (PBMEC) or infused into mammary gland of dairy cows. The messenger RNA (mRNA) from S. uberis associated with PBMEC after 2 h or 4 h of co-culture was purified and sequenced. Results showed that virulence-associated genes such as surface lipoprotein (slp), infection induced histidine kinase (iihK), infection induced response regulator (iirR) and extracellular sugar binding protein 1 and 2 (exsbP1 and exsbP2) were among the top-up-regulated genes. To verify this observation in vivo, quantitative real time PCR (qRT - PCR) was conducted on mRNA of S. uberis recovered from milk of infected mammary glands 24 h post infection. Results revealed that in vitro up-regulated virulence-associated genes were also significantly up regulated under in vivo conditions. The iihK and iirR are flanked by exsbP1 and exsbP2 genes and this entire operon seems to be involved in adaptation to glands micro-environment, survival and colonization of the bovine mammary glands. Based on immunogenic epitope prediction of proteins encoded by these up-regulated genes during early stages of host-bacterial interactions slp, exsbP1 and exsbP2 genes were selected, cloned and expressed in E. coli. The purified recombinant proteins (rSlP, rExsbP1 & rExsbP2) reacted strongly with convalescent serum from cows experimentally infected with S. uberis confirming that they are immunogenic. These proteins may serve as potential targets to develop an effective vaccine against S. uberis mastitis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The TALLYHO (TH) mouse presents a metabolic syndrome of obesity, type 2 diabetes, and hyperlipidemia. Highly significant quantitative trait loci (QTLs) linked to adiposity and hypercholesterolemia were previously identified on chromosome (Chr) 1 in a genome-wide scan of F2 mice from C57BL/6J (B6) x TH. In this study, we generated congenic mouse strains that carry the Chr 1 QTLs derived from TH on a B6 background; B6.TH-Chr1-128Mb (128Mb in size) and B6.TH-Chr1-92Mb (92Mb in size, proximally overlapping). We characterized these congenic mice on chow and high fat (HF) diets. On chow, B6.TH-Chr1-128Mb congenic mice exhibited a slightly larger body fat mass compared with B6.TH-Chr1-92Mb congenic and B6 mice, while body fat mass between B6.TH-Chr1-92Mb congenic and B6 mice was comparable. Plasma total cholesterol levels were significantly higher in B6.TH-Chr1-128Mb congenics compared to B6.TH-Chr1-92Mb congenic and B6 mice. Again, there was no difference in plasma total cholesterol levels between B6.TH-Chr1-92Mb congenic and B6 mice. All animals gained more body fat and exhibited higher plasma total cholesterol levels when fed HF diets than fed chow, but these increases were greater in B6.TH-Chr1-128Mb congenics than in B6.TH-Chr1-92Mb congenic and B6 mice. These results confirmed the effect of the 128Mb TH segment from Chr 1 on body fat and plasma cholesterol values and showed that the distal segment of Chr 1 from TH is necessary to cause both phenotypes. Through bioinformatic approaches, we generated a list of potential candidate genes within the distal region of Chr 1 and tested Ifi202b and Apoa2. We conclude that Chr 1 QTLs largely confer obesity and hypercholesterolemia in TH mice and can be promising targets for identifying susceptibility genes. Congenic mouse strains will be a valuable resource for gene identification.

OBJECTIVE To evaluate changes in behavior and surfactant protein (SP) A and D concentrations in serum and bronchoalveolar lavage fluid (BALF) samples of calves experimentally infected with Mannheimia haemolytica. ANIMALS Twelve 4- to 5-month-old Holstein steers. PROCEDURES Calves were divided into 2 treatment groups and instrumented with a data logger to collect behavioral data. After 10 days of acclimation, calves were experimentally inoculated with 3 × 10 9 CFUs to 5 × 10 9 CFUs of M haemolytica suspended in approximately 5 mL of PBS solution (infected calves; n = 6) or 5 mL of PBS solution without M haemolytica (control calves; 6) through a catheter into the right accessory lung lobe. Calves were clinically evaluated twice daily for 7 days after inoculation. Blood and BALF samples were collected from all calves at predetermined times for determination of serum and BALF SP-A and SP-D concentrations. Serum and BALF concentrations of SP-A and SP-D and behavioral data were evaluated over time and between treatment groups. RESULTS Compared with control calves, infected calves spent more time lying in general and more time lying on the right side during the 24 hours and 6 days after inoculation, respectively. Mean rectal temperature for infected calves (41.3°C) was significantly greater than that for control calves (39.2°C) 12 hours after inoculation. Mean respiratory rate for infected calves (52.5 breaths/min) was significantly greater than that for control calves (45.4 breaths/min) throughout the observation period. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated continuous behavioral monitoring may improve detection of calves with respiratory tract disease.

We developed a reproductive tract size and position score (SPS) system as a reproductive management tool to identify lactating dairy cows with decreased fertility. This system, relying solely on transrectal palpation, considers the size (cervical and uterine) and position of the reproductive tract relative to the pelvis. Cows undergoing pre-breeding exams were identified as having reproductive tracts that were small (SPS1), medium (SPS2), or large (SPS3). Cows designated SPS1 had small and compact uterine horns that rested within the pelvic cavity; SPS2 cows had reproductive tracts that were intermediate in cervical and uterine horn diameter, with longer uterine horns resting partially outside the pelvic cavity; and SPS3 cows had reproductive tracts that were larger and rested mostly outside the pelvic cavity. Cows that were SPS1 had a higher rate of pregnancy per artificial insemination (43.3 ± 3.7%) than cows that were SPS2 (36.9 ± 3.6%) or SPS3 (27.7 ± 4.3%). The percentage of cows with an SPS2 score differed in pregnancies per artificial insemination compared with SPS3 cows. The average days in milk was similar for SPS1, SPS2, and SPS3 cows (104.3 ± 3.5, 98.4 ± 3.4, and 94.7 ± 7.7, respectively). Ultrasound measurements of the uterine horn and cervical diameter, and length measurements of the uterine horns, cervix, and vagina confirmed differences among the SPS groups derived by transrectal palpation. The ease with which transrectal palpation can be used to determine the size and position of the reproductive tract attests to the relevance and usefulness of this scoring system to identify less fertile lactating dairy cows. The ability to do so with ease provides an opportunity to make economically relevant management decisions and maximize reproductive efficiency in a given herd., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim is to identify exposures associated with lung cancer mortality and mortality disparities by race and gender using an exposome database coupled to a graph theoretical toolchain., Methods: Graph theoretical algorithms were employed to extract paracliques from correlation graphs using associations between 2162 environmental exposures and lung cancer mortality rates in 2067 counties, with clique doubling applied to compute an absolute threshold of significance. Factor analysis and multiple linear regressions then were used to analyze differences in exposures associated with lung cancer mortality and mortality disparities by race and gender., Results: While cigarette consumption was highly correlated with rates of lung cancer mortality for both white men and women, previously unidentified novel exposures were more closely associated with lung cancer mortality and mortality disparities for blacks, particularly black women., Conclusions: Exposures beyond smoking moderate lung cancer mortality and mortality disparities by race and gender., Policy Implications: An exposome approach and database coupled with scalable combinatorial analytics provides a powerful new approach for analyzing relationships between multiple environmental exposures, pathways and health outcomes. An assessment of multiple exposures is needed to appropriately translate research findings into environmental public health practice and policy., Competing Interests: Conflicts of interest There are no conflicts of interest.

The aim of this study was to examine relationships among temperament, endocrinology, and reproductive parameters of bulls enrolled in an 84-day performance test. Angus bulls (n = 60) were housed in six pens grouped by age and weight. Pen scores (PS; 1 = docile to 5 = very aggressive) were assigned on Days -1, 27, 55, and 83 of the performance test. On the following day, blood and hair samples were collected, and body weight (BW) and exit velocity (EV) were recorded. Bulls were split into two categories based on; Day -1 PS (PScalm = PS 1 or 2; PSexcitable = PS 3 or 4) and Day 0 EV (EVcalm = slowest 20 bulls; EVexcitable = fastest 20 bulls). Cortisol and testosterone concentrations in serum and hair did not differ (P > 0.10) between PS or EV temperament categories. Sampling day differences (P < 0.01) occurred for serum testosterone, hair cortisol, and hair testosterone concentration; however, serum cortisol concentration did not differ (P > 0.10) over the sampling days. Serum testosterone concentration increased (P < 0.01) from Day 0 to 28, decreased from Day 28 to 56, but Day 84 did not differ from Day 0, 28, or 56. Hair cortisol concentration was greatest (P < 0.01) on Day 0, decreased from Day 28 to 56 but did not differ from Day 56 to 84. Hair testosterone concentration was greatest (P < 0.01) on Day 0 and remained constant from Day 28 to 84. Bulls categorized as PScalm had a greater (P < 0.01) percentage of normal sperm and secondary defects (P < 0.01) when compared with PSexcitable bulls. However, EVcalm bulls had fewer (P < 0.01) primary defects but more (P < 0.01) secondary defects than EVexcitable bulls. In conclusion, bulls exhibited physiological evidence of acclimation during the test as indicated by a reduction in hair cortisol concentration. In addition, the ability of the bulls to acclimate while residing at the testing center may have contributed to little differences observed during the breeding soundness examination portion of the performance test., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Because latent form of matrix metallopeptidase-9 (proMMP9) levels are positively related to blastocyst development, it was hypothesized that addition during maturation may improve development of heat-stressed oocytes. To test hypothesis, 0, 30 or 300 ng/ml human proMMP9 (hMMP9) was added at 18 h of in vitro maturation (hIVM) to cumulus-oocyte complexes matured at 38.5 or 41.0ºC (first 12 h only). Heat stress decreased 24 hIVM proMMP9 levels only in 0 and 30 ng/ml groups and increased progesterone in 0 and 300 ng/ml hMMP9 groups. Heat stress decreased cleavage and blastocyst development. Independent of maturation temperature, hMMP9 at 18 hIVM decreased blastocyst development. In a second study, cumulus-oocyte complexes were matured for 24 h at 38.5 or 41.0ºC (HS first 12 h only) with 0 or 300 ng/ml hMMP9 added at 12 hIVM. Without hMMP9, heat stress decreased 24 hIVM proMMP9 levels and increased progesterone production. Addition of 300 ng/ml of hMMP9 produced equivalent levels of proMMP9 at 24 hIVM (271 vs. 279 ± 77 for 38.5ºC and 41.0ºC treated oocytes, respectively). Heat stress did not affect ability of oocytes to cleave but reduced blastocyst development. Independent of temperature, hMMP9 decreased cleavage and blastocyst development. In summary, hMMP9 supplementation during IVM did not improve development of heat-stressed oocytes even when it was added for the entire maturation period. At doses tested, hMMP9 appeared detrimental to development when supplemented during the last 12 or 6 h of oocyte maturation.

Background: The co-epidemic of obesity and type 2 diabetes is associated with increased morbidity and mortality. Genetic factors are highly involved in the development of these diseases, in the form of interactions of multiple genes within obesogenic and diabetogenic environments, such as a high fat diet. The TALLYHO/Jng (TH) mouse is an inbred polygenic model for human obesity and type 2 diabetes. In order to further develop the TH mouse as a clinically relevant model, we investigated diet dependence of obesity and type 2 diabetes in TH mice vs. C57BL/6 (B6) mice. Results: TH and B6 mice were weaned onto a standard rodent chow, semi-purified high-sucrose low-fat (HSLF), or semi-purified high-sucrose high-fat (HSHF) diet and maintained on these diets throughout the study. Despite similar fat contents in HSLF diets and chow, both B6 and TH mice responded to HSLF diets, with increases in adiposity. TH mice, but not B6 mice, exhibited significantly higher adiposity with severely aggravated glucose intolerance and hyperglycemia on HSHF diets compared to the other diets. HSLF diets also advanced diabetes in TH mice compared to chow, but it did not surpass the effects of HSHF diets. The severe glucose intolerance and hyperglycemia in TH mice on both HSLF and HSHF diets were accompanied by significantly reduced Glut4 mRNA levels compared to B6 mice. Conclusions: The present data demonstrate that diets are important modulators of genetic susceptibility to type 2 diabetes and obesity in TH mice. The interplay between heredity and dietary environment in TH mice appears to amplify insulin resistance, contributing to severe glucose intolerance and diabetes., (© Georg Thieme Verlag KG Stuttgart · New York.)

The dynamics of anion-quadrupole (or anion-π) interactions formed between negatively charged (Asp/Glu) and aromatic (Phe) side chains are for the first time computationally characterized in RmlC (Protein Data Bank entry 1EP0 ), a homodimeric epimerase. Empirical force field-based molecular dynamics simulations predict anion-quadrupole pairs and triplets (anion-anion-π and anion-π-π) are formed by the protein during the simulated trajectory, which suggests that the anion-quadrupole interactions may provide a significant contribution to the overall stability of the protein, with an average of -1.6 kcal/mol per pair. Some anion-π interactions are predicted to form during the trajectory, extending the number of anion-quadrupole interactions beyond those predicted from crystal structure analysis. At the same time, some anion-π pairs observed in the crystal structure exhibit marginal stability. Overall, most anion-π interactions alternate between an "on" state, with significantly stabilizing energies, and an "off" state, with marginal or null stabilizing energies. The way proteins possibly compensate for transient loss of anion-quadrupole interactions is characterized in the RmlC aspartate 84-phenylalanine 112 anion-quadrupole pair observed in the crystal structure. A double-mutant cycle analysis of the thermal stability suggests a possible loss of anion-π interactions compensated by variations of hydration of the residues and formation of compensating electrostatic interactions. These results suggest that near-planar anion-quadrupole pairs can exist, sometimes transiently, which may play a role in maintaining the structural stability and function of the protein, in an otherwise very dynamic interplay of a nonbonded interaction network as well as solvent effects.

Hemlock woolly adelgid (Adelges tsugae [Annand]), an invasive insect in the eastern United States, has caused widespread decline of eastern hemlock, Tsuga canadensis (L.) Carriére. Imidacloprid basal drench treatments were assessed 4-7 yr after a single treatment to determine hemlock woolly adelgid population suppression and effects on hemlock canopy health. The effects of sampling site, years post-treatment, and hemlock diameter at breast height (DBH) size classes were evaluated relative to imidacloprid treatment on hemlock woolly adelgid populations and hemlock canopy health characteristics. The influence of hemlock woolly adelgid populations on canopy health characteristics was also assessed. Imidacloprid treatments resulted in low-level hemlock woolly adelgid populations 7 yr post-treatment. Hemlock woolly adelgid was present on more hemlocks 7 yr compared with 4-6 yr post-treatment. Smaller hemlocks, dosed with 0.7 g active ingredient (AI)/2.5 cm DBH, had higher populations of hemlock woolly adelgid than the largest size class, which were treated at twice that dosage. Concentrations of imidacloprid and its olefin metabolite below the LC 50 were sufficient for suppression of hemlock woolly adelgid populations, which suggests an additive effect of imidacloprid and olefin that compounds hemlock woolly adelgid mortality over many generations. Hemlock woolly adelgid populations observed in this study were too low to have an observable effect on hemlock canopy health, indicating that application intervals of up to 7 yr may be adequate to protect hemlocks., (© The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Alteration of gut microbial colonization process may influence susceptibility of the newborn/infant to infectious and chronic disease. Infectious disease risk leads to widespread use of non-prescription antimicrobials in household products such as Triclocarban (TCC), an antimicrobial compound in personal care products. TCC concentrates in and is transferred through the milk to suckling offspring. TCC exposure during gestation and lactation significantly reduced phylogenetic diversity (PD) among exposed dams and neonates. Among dams using weighted UniFrac distances, TCC induced significant dysbiosis of gut microbiota by gestational day (GD) 18, a trend that continued after delivery. Similarly, an overall restructuring of gut microbiota occurred in neonates. By postnatal day (PND) 12, communities separated based on exposure status and became significantly different at PND 16. The ability of TCC to drive microbial dysbiosis warrants future investigation to evaluate the safety of non-prescription antimicrobial use, including TCC, during critical exposure windows.

Arbuscular mycorrhizal (AM) symbiosis often stimulates gas exchange rates of the host plant. This may relate to mycorrhizal effects on host nutrition and growth rate, or the influence may occur independently of these. Using meta-regression, we tested the strength of the relationship between AM-induced increases in gas exchange, and AM size and leaf mineral effects across the literature. With only a few exceptions, AM stimulation of carbon exchange rate (CER), stomatal conductance (g s), and transpiration rate (E) has been significantly associated with mycorrhizal stimulation of shoot dry weight, leaf phosphorus, leaf nitrogen:phosphorus ratio, and percent root colonization. The sizeable mycorrhizal stimulation of CER, by 49% over all studies, has been about twice as large as the mycorrhizal stimulation of g s and E (28 and 26%, respectively). CER has been over twice as sensitive as g s and four times as sensitive as E to mycorrhizal colonization rates. The AM-induced stimulation of CER increased by 19% with each AM-induced doubling of shoot size; the AM effect was about half as large for g s and E. The ratio of leaf N to leaf P has been more closely associated with mycorrhizal influence on leaf gas exchange than leaf P alone. The mycorrhizal influence on CER has declined markedly over the 35 years of published investigations.

This study compared biomechanics during stair ascent in replaced and non-replaced limbs of total knee arthroplasty (TKA) patients with control limbs of healthy participants. Thirteen TKA patients and fifteen controls performed stair ascent. Replaced and non-replaced knees of TKA patients were less flexed at contact compared to controls. The loading response peak knee extension moment was greater in control and non-replaced knees compared with replaced. The push-off peak knee abduction moment was elevated in replaced limbs compared to controls. Loading and push-off peak hip abduction moments were greater in replaced limbs compared to controls. The push-off peak hip abduction moment was greater in non-replaced limbs compared to controls. Future rehabilitation protocols should consider the replaced knee and also the non-replaced knee and surrounding joints., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Differential Shannon entropy (DSE) and differential coefficient of variation (DCV) are effective metrics for the study of gene expression data. They can serve to augment differential expression (DE), and be applied in numerous settings whenever one seeks to measure differences in variability rather than mere differences in magnitude. A general purpose, easily accessible tool for DSE and DCV would help make these two metrics available to data scientists. Automated p value computations would additionally be useful, and are often easier to interpret than raw test statistic values alone., Results: EntropyExplorer is an R package for calculating DSE, DCV and DE. It also computes corresponding p values for each metric. All features are available through a single R function call. Based on extensive investigations in the literature, the Fligner-Killeen test was chosen to compute DCV p values. No standard method was found to be appropriate for DSE, and so permutation testing is used to calculate DSE p values., Conclusions: EntropyExplorer provides a convenient resource for calculating DSE, DCV, DE and associated p values. The package, along with its source code and reference manual, are freely available from the CRAN public repository at http://cran.r-project.org/web/packages/EntropyExplorer/index.html.

Excitable cattle are dangerous to personnel and have reduced individual performance. The aim of this study was to 1) identify objective criteria for evaluating bull temperament and 2) examine relationships among temperament, behavior, and performance of bulls during an 84-d performance test. Angus bulls ( = 60) were reared in 6 pens based on BW and age. Pen scores (PS; 1 = docile and 5 = very aggressive) were assigned on d -1, 27, 55, and 83. Exit velocity (EV), BW, time to exit the chute, and order through the chute were recorded on d 0, 28, 56, and 84. The ADG was calculated for the 84-d test period, and ultrasound data and frame score calculations were recorded on d 84. Dataloggers measured steps taken, lying time, number of lying bouts, and lying bout duration of bulls ( = 27; 3 pens) from d 3 to 28 and d 59 to 84. Bulls with a d -1 PS of 1 or 2 were categorized as calm (PScalm; = 40), whereas bulls with a PS of 3 or 4 were categorized as excitable (PSexcitable; = 20). Bulls were separated into 2 groups based on the bottom 20 EV (EVcalm) and top 20 EV (EVexcitable) on d 0. Mixed model ANOVA (SAS 9.3) was used to compare groups for the two temperament assessment methods, behavior, and growth performance. Mean EV decreased ( < 0.05) by d 84. Total lying time from d 3 to 28 was greater ( < 0.05) for PScalm bulls when compared with PSexcitable bulls. However, total lying time from d 59 to 84 was greater ( < 0.05) for EVexcitable bulls when compared with EVcalm bulls. Regardless of initial contemporary group assignment, all bulls exited the chute slower ( < 0.001) on d 84 than on d 0. The PSexcitable bulls had greater ( < 0.01) frame scores and greater ADG than PScalm bulls. The PSexcitable bulls had more ( < 0.01) backfat than PScalm bulls. However, ribeye area was smaller ( < 0.01) in EVexcitable bulls than EVcalm bulls. Based on these results, bulls appeared to have habituated over the testing period. Additionally, the potential lack of innate temperament variation may have attributed to the little difference seen among the behavioral and performance data. Therefore, temperament should be reassessed within a novel environment with new handlers to differentiate between the bull's true temperament and its ability to habituate.