Low Animals Research Articles

Relationships between the genes expressed in the mesenteric adipose tissue of beef cattle and feed intake and gain.

Mesenteric fat, a depot within the visceral fat, accumulates in cattle during maturation and finishing and may be a potential source of production inefficiency. The aim of this study was to determine whether the genes expressed in the mesenteric fat of steers were associated with body weight gain and feed intake. Sixteen steers chosen by their rank of distance from the bivariate mean for gain and feed intake were used for this study. Mesenteric fat was obtained and evaluated for differences in gene expression. A total of 1831 genes were identified as differentially expressed among steers with variation in feed intake and gain. Many of these genes were involved with metabolic processes such as proteolysis, transcription and translation. In addition, the Gene Ontology annotations including transport and localization were both over-represented among the differentially expressed genes. Pathway analysis was also performed on the differentially expressed genes. The superoxide radical degradation pathway was identified as over-represented based on the differential expression of the genes GPX7, SOD2 and TYRP1, suggesting a potential role for oxidative stress or inflammatory pathways among low gain-high intake animals. GPX7 and SOD2 were in lower transcript abundance, and TYRP1 was higher in transcript abundance among the low gain-high feed intake animals. The retinoate biosynthesis pathway was also enriched due to the differential expression of the genes AKR1C3, ALDH8A1, RDH8, RDH13 and SDR9C7. These genes were all more highly expressed in the low gain-high intake animals. The glycerol degradation and granzyme A signaling pathways were both associated with gain. Three glycerol kinase genes and the GZMA gene were differentially expressed among high vs. low gain animals. Mesenteric fat is a metabolically active tissue, and in this study, genes involved in proteolysis, transcription, translation, transport immune function, glycerol degradation and oxidative stress were differentially expressed among beef steers with variation in body weight gain and feed intake.

Gene expression of behaviorally relevant genes in the cerebral hemisphere changes after selection for tameness in Red Junglefowl.

The process of domestication in animals has led to alterations in behavior, physiology and phenotypic traits, changes that may be driven by correlations with reduced fear of humans. We used Red Junglefowl, ancestors of all domesticated chickens selected for either high or low fear of humans for five generations to study the effects of selection on gene transcription in the cerebral hemisphere, which is heavily involved in behaviour control. A total of 24 individuals from the parental generation as well as from the fifth selected generation were used. Twenty-two genes were significantly differentially expressed at p < 0.05 after false discovery rate (FDR) correction. Those genes that were upregulated in the low fearful animals were found to be involved in neural functions. Gene ontology and pathway analysis revealed enrichment for terms associated with behavioural processes. We conclude that five generations of divergent selection for high or low tameness has significantly changed gene expression patterns in the cerebral hemisphere in the Red Junglefowl population used here, which could underlie a range of changes in the domestic phenotype.

Eficiencia alimentaria en dos líneas divergentes para variabilidad ambiental del peso al nacimiento en ratones

The feed efficiency is one of the main objectives in livestock production because feeding is the highest cost in animal production. The objective of this study was to compare the feed efficiency in two divergent lines for the birth weight environmental variability in mice. The results showed that the weekly feed intakes were lower in the low line than the high line in some periods. These differences could be related with the lower weight in the low line. The cumulated feed intake index didn’t show significant differences between lines. The robustness of low variability animals seems not to produce differences regarding feed efficiency, but probably low variability animals could respond better to an environmental challenge taking benefit to increase its survival.

Nerve degeneration and regeneration in the cephalopod mollusc Octopus vulgaris: the case of the pallial nerve

Regeneration is a process that restores structure and function of tissues damaged by injury or disease. In mammals complete regeneration is often unsuccessful, while most of the low phyla animals can re-grow many parts of their body after amputation. Cephalopod molluscs, and in particular Octopus vulgaris, are well known for their capacity to regenerate their arms and other body parts, including central and peripheral nervous system. To better understand the mechanism of recovery following nerve injury in this species we investigated the process of axon regrowth and nerve regeneration after complete transection of the Octopus pallial nerves. This injury induces scar formation and activates the proliferation of hemocytes which invade the lesion site. Hemocytes appear involved in debris removal and seem to produce factors that foster axon re-growth. Connective tissue is involved in driving regenerating fibers in a single direction, outlining for them a well-defined pathway. Injured axons are able to quickly re-grow thus to restoring structure and function.

Residual feed intake, carcass traits and meat quality in Nellore cattle

A total of 127 Nellore bulls classified as low and high residual feed intake (RFI), from three selection lines, were evaluated in five experiments aiming to identify associations between RFI, carcass, and meat quality traits. Feedlot performance, carcass traits, and meat quality of Longissimus muscle were evaluated. A mixed model including the fixed effects of RFI class, selection line, interaction between RFI class and selection line, and age at slaughter as a covariate, and the random effects of diet within experiment and experiment was used, with means compared by the t-test. Feed intake average difference was 0.962kg/day; low RFI animals consumed 0.479kg/day less feed and high RFI animals consumed 0.483kg/day more feed than expected. No differences between RFI classes were detected for most of studied variables, demonstrating the absence of unfavorable associations between RFI and carcass and meat quality traits. Low RFI Nellore animals use feed efficiently and produce good quality carcasses and meat.

RdRP-synthesized antisense ribosomal siRNAs silence pre-rRNA via the nuclear RNAi pathway.

Expression of rRNA affects cell growth and proliferation, but mechanisms that modulate rRNA levels are poorly understood. We conducted a genetic screen for factors that negatively regulate generation of endogenous short interfering RNA (endo-siRNA) in Caenorhabditis elegans and identified a suppressor of siRNA (susi-1) and antisense ribosomal siRNAs (risiRNAs). risiRNAs show sequence complementary to 18S and 26S rRNAs and require RNA-dependent RNA polymerases (RdRPs) for their production. They act through the nuclear RNA interference (RNAi) pathway to downregulate pre-rRNA. Stress stimuli, including low temperature and UV irradiation, induced the accumulation of risiRNAs. SUSI-1 is a homolog of the human DIS3L2 exonuclease involved in 3'-5' degradation of oligouridylated RNAs. In susi-1 mutant and in low temperature-treated animals, 3'-tail oligouridylated 26S rRNA accumulated. The injection of oligouridylated rRNA elicited nuclear accumulation of NRDE-3. Our findings identify a new subset of 22G-RNAs that regulate pre-rRNA expression and a mechanism to maintain rRNA homeostasis.

Abstract PR03: The pig as a model for colorectal cancer

Abstract Colorectal cancer is the fourth most common cancer worldwide with a mortality of more than 50%. Contrary to the increasing advances in cancer research colorectal cancer deaths are increasing in number. Most animal models also for colorectal cancer are in rodents. However, mice differ significantly in size, lifespan, physiology, anatomy and diet. Furthermore, genetically engineered mouse models for colorectal cancer show polyp development in the small intestine, contrary to the human phenotype that develops polyps in the large intestine. Therefore, a more suitable animal model is necessary. Pigs are increasingly recognized as a valuable model facilitating diagnostic and therapeutic strategies at human scale, longitudinal studies of disease initiation, progression and treatment response in preclinical trials. We generated gene targeted cloned pigs carrying the nonsense mutation, APC1311 that is orthologous to a human mutation associated with a very severe phenotype of colorectal cancer and the inherited condition familial adenomatous polyposis (FAP). In pigs the APC1311 mutation results in multiple adenomatous polyps in the colon and rectum that, so far, have progressed to carcinoma in situ. Histological and molecular analysis show that the porcine model recapitulates all major features of early stage human FAP. Breeding and analysis of the mutant pig herd has revealed segregation of traits that affect polyposis severity in animals carrying the same APC1311 mutation. We are currently investigating the genetic basis for this effect by comparing normal mucosa samples from low and high polyp animals and have discovered some genes that are differentially expressed. A progression study comparing low-grade with high-grade adenomas also identified differentially expressed genes and miRNAs. Further improvements of this model are targeted at generating organ/tissue specific Cre pigs to activate latent mutations such as KRAS and TP53 mutations in the colon. Additionally to encourage cancer progression we are working on the introduction of ubiquitous Cas9 expression in our APC1311 pigs to allow the activation of oncogenic pathways locally in vivo. Our porcine model provides a powerful new resource for preclinical cancer research, including identifying and investigating novel biomarkers for early detection. This abstract is also being presented as Poster A20. Citation Format: Carolin Wander, Tatiana Flisikowska, Krzysztof Flisikowski, Érica Schulze, Hans-Rudolf Fries, Stefan Bauersachs, Alexander Kind, Angelika Schnieke. The pig as a model for colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr PR03.

Digestion and metabolism of low and high residual feed intake Nellore bulls.

Understanding the reasons why animals of similar performances have different feed requirements is important to increase profits for cattle producers and to decrease the environmental footprint of beef cattle production. This study was carried out aiming to identify the associations between residual feed intake (RFI) and animal performance, nutrient digestibility, and blood metabolites related to energy balance of young Nellore bulls during the finishing period. Animals previously classified as low (n = 13) and high RFI (n = 12), with average initial body weight of 398kg and age of 503days were used. Cattle were fed a high energy diet and were slaughtered when rib fat thickness measured by ultrasound between the 12th and 13th ribs reached the minimum of 4mm. A completely randomized design was adopted, being data analyzed with a mixed model that included the random effect of slaughter group, the fixed effect of RFI class, and linear effect of the covariate feedlot time. No differences were found (p > 0.10) between RFI classes for performance, dry matter, and nutrients intake. However, dry (p = 0.0911) and organic matter (p = 0.0876) digestibility tended to be lower, and digestibility of neutral detergent fiber corrected for ash and protein (p = 0.0017), and total digestible nutrients (p = 0.0657) were lower for high RFI animals, indicating lesser capacity of food utilization. Difference between low and high RFI animals was also found for blood cortisol at the end of the trial (p = 0.0044), having low RFI animals lower cortisol concentrations. Differences in the ability to digest food can affect the efficiency of transforming feed into meat by Nellore cattle.

Residual Feed Intake as a Tool for Selecting More Efficient Animals: A Review

Feeds alone contributes about 60–70% of total cost of ruminant's production. There is deficiency to the tune of 10, 37 and 35% for dry fodder, concentrates and green fodders, respectively in India. Therefore, selection of efficient animals could help in reducing the burden of already scarce feed resources. A significant improvement in profitability could be achieved through a reduction in production costs by implementation of selection strategies to improve feed efficiency. There are several measures of feed efficiency viz., feed conversion ratio, relative growth rate, partial efficiency of growth, gross efficiency and residual feed intake (RFI). RFI is difference between actual feed intake and the feed an animal is expected to consume based on its body size and growth rate. Cattle with low RFI eat less than expected for their weight and growth rate and are, therefore, more efficient than cattle with high RFI. Among the feed efficiency measures, RFI is considered to be the best as it is moderately heritable (h2=0.29–0.46) and phenotypically independent of growth rate and body weight in growing cattle and basically reflects the variation in animal's maintenance. This makes RFI as selection tool for efficient animals. About one-third of the biological variation in RFI of these calves could be explained by differences in feed intake (2%), digestion (10%), heat increment (9%), composition of gain (5%) and activity (5%) while the remaining variation in RFI was related to differences in protein turnover, stress and tissue metabolism (37%) and differences in cellular energy expenditures such as ion pumping and mitochondrial proton leakage (27%). The low RFI animals consume less feed and produce less enteric methane. hence, there are economic and environmental benefits by selecting such efficient animals. Phenotypic selection for RFI poses challenges because it requires measurement of each individual's feed intake for a minimum of 70 days which is expensive, time and labour intensive. As a result, there is need to develop alternative approaches like biochemical and physiological markers which could differentiate between high and low RFI animals within short period of time. Recently, genomic selection is being used as an appealing alternative tool for selection of low RFI animals. However, such studies need to be conducted using large number of animals so that more efficient animals could be selected for future breeding programmes for economic and environmental benefits.

Ultrasound-Stimulated Drug Delivery Using Therapeutic Reconstituted High-Density Lipoprotein Nanoparticles.

The abnormal tumor vasculature and the resulting abnormal microenvironment are major barriers to optimal chemotherapeutic drug delivery. It is well known that ultrasound (US) can increase the permeability of the tumor vessel walls and enhance the accumulation of anticancer agents. Reconstituted high-density lipoproteins (rHDL) nanoparticles (NPs) allow selective delivery of anticancer agents to tumor cells via their overexpressed scavenger receptor type B1 (SR-B1) receptor. The goal of this study is to investigate the potential of noninvasive US therapy to further improve delivery and tumor uptake of the payload from rHDL NPs, preloaded with an infrared dye (IR-780), aimed to establish a surrogate chemotherapeutic model with optical localization. Athymic nude mice were implanted orthotopically with one million breast cancer cells (MDA-MB-231/Luc). Three weeks later, animals were divided into seven groups with comparable mean tumor size: control, low, moderate, and high concentration of rHDL NPs alone groups, as well as these three levels of rHDL NPs plus US therapy groups (N = 7 to 12 animals per group), where low, moderate and high denote 5, 10, and 50 µg of the IR-780 dye payload per rHDL NP injection, respectively. The US therapy system included a single element focused transducer connected in series with a function generator and power amplifier. A custom 3D printed cone with an acoustically transparent aperture and filled with degassed water allowed delivery of focused US energy to the tumor tissue. US exposure involved a pulsed sequence applied for a duration of 5 min. Each animal in the US therapy groups received a slow bolus co-injection of MB contrast agent and rHDL NPs. Animals were imaged using a whole-body optical system to quantify intratumoral rHDL NP accumulation at baseline and again at 1 min, 30 min, 24 h, and 48 h. At 48 h, all animals were euthanized and tumors were excised for ex vivo analysis. We investigated a noninvasive optical imaging method for monitoring the effects of US-stimulated drug delivery of IR-780 dye-loaded rHDL NPs in living animals. No change in optical imaging data was found in the control animals. However, there was considerable dye accumulation (surrogate drug) within 48 h in the low (5 µg), moderate (10 µg), and high (50 µg) rHDL NP concentration-dosed group animals (p < 0.09). With US therapy added to the experimental protocol, there was an additional and significant increase in local tumor drug uptake at 48 h (p < 0.02). Optical image data collected from ex vivo tumor samples confirmed tumor retention of the IR-780 dye-loaded rHDL NPs and correlated positively with in vivo optical imaging results (R2 > 0.69, p < 0.003). IR-780 dye extraction from the tumor tissue samples confirmed the in vivo and ex vivo US therapy findings. Overall, the addition of US therapy considerably improved local rHDL NP accumulation in tumor tissue. This study concludes that US-mediated drug delivery can facilitate tumor uptake of rHDL NPs and more research is warranted to optimize the drug dosing schedule and the respective therapeutic protocols.

Detection of residues in urine and tissues of sheep treated with trace levels of dietary ractopamine HCl.

Qualitative assays are sometimes used as the sole basis for detecting drug residues in live animals or in animal products. Such assays have become increasingly sensitive as detection technologies have improved, yet the limitations of such assays to discriminate purposeful and accidental drug exposures remain poorly defined. A study was conducted to determine the ability of a ractopamine lateral flow assay to accurately detect incurred ractopamine residues in contaminated feeds and in sheep fed trace quantities of ractopamine HCl. False positive and negative samples were determined using a quantitative liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. Ractopamine HCl was fed to sheep at 0 (Zero), 1 (Low), 10 (Med), or 100 (High) µg/kg of diet ( = 4 per level, 0.5 kg of feed/d) for 7 consecutive d and urine was collected daily about ∼16 h post exposure. On-site lateral flow assays were able to reliably (0% false negatives) detect 20 μg of ractopamine HCl per kg of feed. Urine from treated sheep tested positive for ractopamine residues by lateral flow assay in 7.4 (Zero), 0 (Low), 82 (Med), and 86% (High) of the urine samples from each group. Parent ractopamine was below the assay limit of quantification (LOQ, 0.7 ng/mL) in all urine samples using LC-MS/MS. After hydrolysis of ractopamine conjugates, total ractopamine (parent + hydrolyzed metabolites) in urine of Low animals was always less than the LOQ, but in 7 of 28 samples were above the limit of detection (LOD, 0.22 ng/mL). In contrast, urine in Med animals contained 1.08 to 9.13 ng/mL of total ractopamine, while urine of High animals contained 4.85-32.82 ng/mL of total ractopamine. Ractopamine is rapidly eliminated; nevertheless, > 80% of urine samples from sheep exposed to 5 µg/d (M) of ractopamine HCl had detectable residues by the screening assay and a 100% of samples had measurable ractopamine using LC-MS/MS methods. Tissue residues of ractopamine were not detected in any of the sheep. The sensitivity with which the rapid, qualitative assay detected ractopamine was sufficient to reveal trace ractopamine exposures; these data suggest that the use of qualitative tests to indicate purposeful treatment of animals (i.e., for doping or growth enhancement), in the absence of collaborating quantitative data, is inappropriate.

Maternal care and affective behavior in female offspring: Implication of the neurosteroid/GABAergic system

In female rats, the proestrus phase of the estrous cycle is associated with decreased levels of anxiety-like and depressive-like behavior relative to the metestrus phase. Progesterone likely modulate these behaviors, in part through the influence of its metabolite, allopregnanolone (THP) on hippocampal GABAAR subunit expression. As natural variations in maternal care have been found to influence both progesterone levels at proestrus and anxiety-like behavior in female offspring, we sought to investigate the importance of maternal care and the estrous cycle on affective behavior in female rats that had received Low or High levels of licking/grooming (LG) during early life. Subjects were tested for anxiety-like behavior in the elevated plus maze at proestrus or metestrus or for estrous cycle-dependent changes in depressive-like anhedonic behavior with a saccharin preference test. GABAAR subunit expression, and THP levels in the dorsal hippocampus and in plasma were also evaluated. Estrous cycle phase influenced saccharine preference and hippocampal THP level in both phenotypes. Low LG animals showed higher levels of hedonic behavior and anxiety-like behavior, irrespective of estrous cycle phase, as well as lower THP levels within the dorsal hippocampus when compared to High LG animals. Only High LG animals showed positive correlations between hippocampal THP levels and GABAAR subunit expression, suggesting a relative insensitivity to THP’s modulation of these receptor subunits in Low LG offspring. These findings suggest that natural variations in maternal care influence anxiety-like and hedonic behavior through the modulation of the neurosteroid/GABAergic system.

Clinical, diagnostic and pathologic features of presumptive cases of Chlamydia pecorum-associated arthritis in Australian sheep flocks.

BackgroundArthritis is an economically significant disease in lambs and is usually the result of a bacterial infection. One of the known agents of this disease is Chlamydia pecorum, a globally recognised livestock pathogen associated with several diseases in sheep, cattle and other hosts. Relatively little published information is available on the clinical, diagnostic and pathologic features of C. pecorum arthritis in sheep, hindering efforts to enhance our understanding of this economically significant disease. In this case series, a combination of standard diagnostic testing used routinely by veterinarians, such as the Chlamydia complement fixation text (CFT), veterinary clinical examinations, and additional screening via C. pecorum specific qPCR was used to describe putative chlamydial infections in five sheep flocks with suspected ovine arthritis.Case presentationFive separate cases involving multiple lambs (aged six to ten months) of different breeds with suspected C. pecorum arthritis are presented. In two of the five cases, arthritic lambs exhibited marked depression and lethargy. Arthritis with concurrent conjunctivitis was present in four out of five lamb flocks examined. Chlamydia CFT demonstrated medium to high positive antibody titres in all flocks examined. C. pecorum shedding was evident at multiple sites including the conjunctiva, rectum and vagina, as determined via qPCR. Two of the five flocks received antimicrobials and all flocks recovered uneventfully regardless of treatment.ConclusionThis case series highlights the features a field veterinarian may encounter in cases of suspected ovine chlamydial arthritis. Our analysis suggests a presumptive diagnosis of chlamydial arthritis in lambs can be made when there is evidence of joint stiffness with or without synovial effusion and elevated chlamydia antibody titres. C. pecorum-specific qPCR was found to be a useful ancillary diagnostic tool, detecting Chlamydia positivity in low or negative CFT titre animals. Variables such as symptom duration relative to sampling, sheep breed and farm management practices were all factors recorded that paint a complex epidemiological and diagnostic picture for this disease. These case studies serve to provide a platform for further research to improve diagnostic testing and new treatment and control strategies for C. pecorum infections in sheep.

Impact of selection for residual feed intake on production traits and behavior of mule ducks

A divergent selection experiment of Muscovy sires based on the residual feed intake (RFI) of their male mule progeny was initiated in 2009. Using electronic feeders, the aim of this study was to establish whether 3 generations of selection for RFI had an impact on feeding behavior traits and general behavior, and to examine its effect on liver and meat quality. Eighty mule ducks, issued from 8 Muscovy drakes per line with extreme RFI, were tested in a pen equipped with 4 electronic feeders. Feeding behaviors were recorded from 3 to 7 wk after hatching under ad libitum feeding conditions. Then animals were prepared for overfeeding with a 3-week period of restricted feeding, and overfed during 12 d before slaughter. The RFI was significantly lower in the low RFI line than in the high RFI line (−5.4 g/d, P = 0.0005) and daily feed intake was reduced both over the entire test period (−5 g/d, P = 0.049) and on a weekly basis (P = 0.006). Weekly and total feed conversion ratios were also significantly lower (−0.08, P = 0.03 and −0.06, P = 0.01, respectively). Low RFI ducks had more frequent meals, spent as much time eating as high RFI ducks, and their feeding rate was lower when analyzed at the wk level only. Additionally no significant correlation between feed efficiency and feeding behavior traits was evidenced, indicating only limited relationships between RFI and feeding patterns. Some differences in behavioral responses to stressors (open field test combined with a test measuring the response to human presence) suggested that a lower RFI is associated with less fearfulness. Selection for RFI had no effect on liver weight and quality and a slightly deleterious impact on meat quality (decreased drip loss and L*). Finally, low RFI animals had higher body weights after restricted feeding from wk 10 to wk 12 and after overfeeding than high RFI ducks. This suggests that selection for reduced RFI until 7 wk of age increases the feed efficiency up to slaughter.

Profile of the Spleen Transcriptome in Beef Steers with Variation in Gain and Feed Intake.

We have previously identified components of the immune system contributing to feed intake and gain in both the rumen and small intestine of beef steers. In this study, we examined the spleen, a major lymphatic organ near the digestive tract, to determine whether it was also influencing individual feed efficiency status through immune responses. Animals (n = 16) that were divergent for gain and intake were selected for tissue sampling. The spleen transcriptomes were evaluated by microarray. A total of 1216 genes were identified as differentially expressed. Genes were over-represented in Kyoto encyclopedia of genes and genomes (KEGG) pathways including biological regulation, protein folding, cell communication, immune systems process, response to stress, and RNA metabolic process. Several stress response or heat shock genes including HSPH1, HSPA1A, HSPA4, DNAJB4, DNAJA4, etc., were identified as a stress response functional gene cluster in the low gain-low intake animals. These genes were up-regulated amongst the low gain-low intake animals compared to all other groups. Canonical pathways associated with the differentially expressed genes included the coagulation system, extrinsic prothrombin activation, protein ubiquitination, unfolded protein response, and aldosterone signaling in epithelial cells. An analysis of expressed copy number variable (CNV) genes in the spleen produced some of the same genes and gene families that were differentially expressed. Our data suggests the splenic contribution to some of the underlying variation among gain and intake within this group of animals may be a result of immune function and stress response. In addition, some of the differences in immune response functions may be related to gene copy number.

IL-15 enhances the anti-tumor activity of trastuzumab against breast cancer cells but causes fatal side effects in humanized tumor mice (HTM).

Cancer immunotherapy has been shown to enhance established treatment regimens. We evaluated the potential reinforcing effect of IL-15 in trastuzumab treated humanized tumor mice (HTM) which were generated by concurrent transplantation of neonatal NOD-scid IL2Rγnull mice with human hematopoietic stem cells (HSC) and HER2 positive breast cancer cells (metastasizing SK-BR-3, solid tumor forming BT474).We found that trastuzumab treatment efficacy mainly depends on the immediate anti-tumorigenic cellular effect which is significantly enhanced by tumor interacting immune cells upon cotransplantion of HSC. However, trastuzumab treatment caused elevated CD44 expression on tumor cells that metastasized into the lung and liver but did not hinder tumor cell dissemination into the bone marrow. Moreover, in a number of SK-BR-3-transplanted animals disseminated CD44high/CD24low tumor cells lost trastuzumab sensitivity. Concerning the FcγRIIIa polymorphism, trastuzumab treatment efficiency in HTM was higher in mice with NK-cells harboring the high affinity FcγRIIIa compared to those with low affinity FcγRIIIa. In contrast, IL-15 caused the strongest NK-cell activation in heterozygous low affinity FcγRIIIa animals. Although IL-15 enhanced the trastuzumab mediated tumor defense, an unspecific immune stimulation resulted in preterm animal death due to systemic inflammation. Overall, treatment studies based on “patient-like” HTM revealed critical and adverse immune-related mechanisms which must be managed prior to clinical testing.

Low proviral small ruminant lentivirus load as biomarker of natural restriction in goats

Small ruminant lentiviruses (SRLV) globally affect welfare and production of sheep and goats and are mainly controlled through elimination of infected animals, independently of the viral kinetics within the single animal. Control programs are based on highly sensitive serological tests, however the existence of low antibody responders leads to the permanent presence of seronegative infected animals in the flock, thus perpetuating the infection. On the other hand, long-term non-progressors show a detectable antibody response not indicative of a shedding animal, suggesting immune contention of infection.In this study, we analyse two goat populations within the same herd, harbouring low or high proviral SRLV loads respectively, both showing a robust antibody response. In vivo findings were confirmed in vitro since fibroblastic cell lines obtained from one high and one low proviral load representative goats, showed respectively a high and a faint production of virus upon infection with reference and field circulating SRLV strains. Differences in virus production were relieved when strain CAEV-Co was used for experimental infection. We analysed LTR promoter activity, proviral load, entry step and production of virus and viral proteins. Intriguingly, proteasomal activity was higher in fibroblasts from low proviral load animals and proteasome inhibition increased viral production in both cell lines, suggesting the implication of active proteasome-dependent restriction factors. Among them, we analysed relative expression and sequences of TRIM5α, APOBEC3 (Z1, Z2, Z3 and Z2-Z3) and BST-2 (Tetherin) and found a global antiviral status in low proviral carriers that may confer protection against viral shedding and disease onset.

Differential gene expression in the duodenum, jejunum and ileum among crossbred beef steers with divergent gain and feed intake phenotypes.

Small intestine mass and cellularity were previously associated with cattle feed efficiency. The small intestine is responsible for the digestion of nutrients and absorption of fatty acids, amino acids and carbohydrates, and it contributes to the overall feed efficiency of cattle. The objective of this study was to evaluate transcriptome differences among the small intestine from cattle with divergent gain and feed intake. Animals most divergent from the bivariate mean in each of the four phenotypic Cartesian quadrants for gain×intake were selected, and the transcriptomes of duodenum, jejunum and ileum were evaluated. Gene expression analyses were performed comparing high gain vs. low gain animals, high intake vs. low intake animals and each of the phenotypic quadrants to all other groups. Genes differentially expressed within the high gain-low intake and low gain-high intake groups of animals included those involved in immune function and inflammation in all small intestine sections. The high gain-high intake group differed from the high gain-low intake group by immune response genes in all sections of the small intestine. In all sections of small intestine, animals with low gain-low intake displayed greater abundance of heat-shock genes compared to other groups. Several over-represented pathways were identified. These include the antigen-processing/presentation pathway in high gain animals and PPAR signaling, starch/sucrose metabolism, retinol metabolism and melatonin degradation pathways in the high intake animals. Genes with functions in immune response, inflammation, stress response, influenza pathogenesis and melatonin degradation pathways may have a relationship with gain and intake in beef steers.

Important role of dominance in allogrooming behaviour in beef cattle

In domestic cattle, the relationship between dominance and allogrooming behaviour has been investigated in several studies. However, the results do not show a consistent pattern. The aim of this study was to investigate this relationship in a stable female beef cattle herd using social network analysis as a novel methodological approach. We tested two adaptive allogrooming hypotheses. The ‘Grooming-for-Commodity’ hypothesis posits that allogrooming is directed from low ranking animals towards higher ranking cows in exchange of tolerance and other favours. The ‘Grooming-for-Stability’ hypothesis predicts that allogrooming is performed by high ranking animals down the hierarchy in order to perpetuate the stability of the social structure. We recorded a herd of 15 Gasconne cows on pasture for 3 weeks (180h) and recorded 681 agonistic interactions and 288 allogrooming events. To evaluate the relationship between dominance and allogrooming behaviour we calculated correlations between dominance index, individual behavioural effort (OUT-direction), and individual attractiveness (IN-direction). We found that more dominant animals provided much higher amount of allogrooming acts (p<0.001) and groomed more herdmates (p<0.001). As a consequence, allogrooming behaviour was mostly oriented down the hierarchy (p<0.001). At the same time, more dominant animals also received higher total number of allogrooming (p<0.05). This seeming paradox was due to the fact that the very active high ranking allogroomers exchanged a lot of the licking with each other. Further, the dominance index of the cow was or tended to be positively related to the social network analysis measures of IN-Dyad-Reciprocity (p=0.065), IN-Betweenness (p<0.05) and OUT-Dyad-Reciprocity (p<0.001). Our study showed that the more dominant animals have more prominent roles in the allogrooming network of a stable female beef cattle herd. These results give more support to the ‘Grooming-for-Stability’ hypothesis than to the ‘Grooming-for-Commodity’ hypothesis.

Recent Advances in Measurement and Dietary Mitigation of Enteric Methane Emissions in Ruminants.

Methane (CH4) emission, which is mainly produced during normal fermentation of feeds by the rumen microorganisms, represents a major contributor to the greenhouse gas (GHG) emissions. Several enteric CH4 mitigation technologies have been explored recently. A number of new techniques have also been developed and existing techniques have been improved in order to evaluate CH4 mitigation technologies and prepare an inventory of GHG emissions precisely. The aim of this review is to discuss different CH4 measuring and mitigation technologies, which have been recently developed. Respiration chamber technique is still considered as a gold standard technique due to its greater precision and reproducibility in CH4 measurements. With the adoption of recent recommendations for improving the technique, the SF6 method can be used with a high level of precision similar to the chamber technique. Short-term measurement techniques of CH4 measurements generally invite considerable within- and between-animal variations. Among the short-term measuring techniques, Greenfeed and methane hood systems are likely more suitable for evaluation of CH4 mitigation studies, if measurements could be obtained at different times of the day relative to the diurnal cycle of the CH4 production. Carbon dioxide and CH4 ratio, sniffer, and other short-term breath analysis techniques are more suitable for on farm screening of large number of animals to generate the data of low CH4-producing animals for genetic selection purposes. Different indirect measuring techniques are also investigated in recent years. Several new dietary CH4 mitigation technologies have been explored, but only a few of them are practical and cost-effective. Future research should be directed toward both the medium- and long-term mitigation strategies, which could be utilized on farms to accomplish substantial reductions of CH4 emissions and to profitably reduce carbon footprint of livestock production systems. This review presents recent developments and critical analysis on different measurements and dietary mitigation of enteric CH4 emissions technologies.