The dietary inclusion of feed additives to improve the carcass characteristics of the final product is of great importance for the pork production chain. The aim of our study was to evaluate the effects of the association of ractopamine (RAC) and conjugated linoleic acid (CLA) on the performance traits of finishing pigs during the last 26 days prior to slaughter. In total, 810 commercial hybrid barrows were used. Animals were distributed among treatments according to a randomised block design in a 3 × 3 factorial arrangement, with three RAC levels (0, 5 or 10 ppm) and three CLA levels (0, 0.3 or 0.6%). Pigs fed the diet with 5 ppm RAC had higher average daily feed intake (ADFI) (2.83 kg; P < 0.05) when compared with those fed 10 ppm RAC and the control diet (2.75 and 2.74 kg, respectively). Lower ADFI values (P < 0.01) were observed with the diets containing CLA compared with the control diet with no CLA (2.73 and 2.75 v. 2.85 kg/day, respectively). The average daily weight gain of pigs fed 5 and 10 ppm RAC was +148 and +173 g/dayhigher (P < 0.001), respectively, than those fed the control diet. Dietary RAC levels influenced (P < 0.001) feed conversion ratio (FCR), which was reduced as RAC levels increased, with the pigs fed 10, 5 and 0 ppm RAC presenting FCR values of 2.57, 2.71 and 3.05, respectively. FCR also improved (P < 0.05) with the inclusion of 0.6% CLA relative to the control diet (2.70 v. 2.84, respectively). There was a significant interaction between CLA × RAC levels (P < 0.01) for final BW, loin eye area (LEA) (P < 0.05) and backfat thickness (BT) (P < 0.05). The treatments containing 10 ppm RAC + 0.6% or 0.3% CLA increased LEA and reduced BT. In conclusion, the level of 10 ppm inclusion of RAC increased the overall performance parameters of pigs and therefore improved production efficiency. The combined use of RAC and CLA promoted a lower feed conversion ratio as well as better quantitative carcass traits, as demonstrated by the higher LEA and lower BT. The dietary inclusion of CLA at 0.3% improved feed efficiency, however, without affecting LEA or BT yields.

Background: Hereditary transthyretin-mediated (hATTR) amyloidosis a hereditary, multi-systemic and life-threatening disease resulting in neuropathy and cardiomyopathy. In the APOLLO study, patisiran, an investigational RNAi therapeutic targeting hepatic TTR production resulted in significant improvement in neuropathy and QoL compared to placebo and was generally well tolerated. Methods: APOLLO, a Phase 3 study of patisiran vs. placebo (NCT01960348) prespecified a cardiac subpopulation (n=126 of 225 total) that included patients with baseline left ventricular (LV) wall thickness ≥ 13mm and no medical history of aortic valve disease or hypertension. Cardiac measures included structure and function by electrocardiography, changes in NT-proBNP and 10-MWT gait speed. Results: At 18 months, patisiran treatment resulted in a mean reduction in LV wall thickness of 1 mm (p=0.017) compared to baseline, which was associated with significant improvements relative to placebo in LV end diastolic volume (+8.31 mL, p=0.036), global longitudinal strain (-1.37%, p=0.015) and NT-proBNP (55% reduction, p=7.7 x 10-8) (Figure 1). Gait speed was also improved relative to placebo (+0.35 m/sec, p=7.4 x 10-9). Rate of death or hospitalization was lower with patisiran. mNIS+7 results in the cardiac subpopulation will also be presented. Conclusions: These data suggest patisiran has the potential to halt or reverse cardiac manifestations of hATTR amyloidosis.

In the current study, phage-exposed mimotopes as targets against tegumentary leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of TL patients and healthy subjects, besides the immune stimulation of peripheral blood mononuclear cells (PBMCs) collected from untreated and treated TL patients and healthy subjects. The clones were evaluated regarding their specific interferon-γ (IFN-γ) and interleukin-4 (IL-4) production in the in vitro cultures, and selectivity and specificity values were calculated, and those presenting the best results were selected for the in vivo experiments. Two clones, namely A4 and A8, were identified and used in immunization protocols from BALB/c mice to protect against Leishmania amazonensis infection. Results showed a polarized Th1 response generated after vaccination, being based on significantly higher levels of IFN-γ, IL-2, IL-12, tumour necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF); which were associated with lower production of specific IL-4, IL-10 and immunoglobulin G1 (IgG1) antibodies. Vaccinated mice presented significant reductions in the parasite load in the infected tissue and distinct organs, when compared with controls. In conclusion, we presented a strategy to identify new mimotopes able to induce Th1 response in PBMCs from TL patients and healthy subjects, and that were successfully used to protect against L. amazonensis infection.

The present study aimed to evaluate the mechanisms modulated by dietary arginine supplementation to sows during lactation regarding antioxidant capacity and vascularization of mammary glands. At 109 days of gestation, animals were transferred to individual farrowing crates equipped with manual feeders and automatic drinker bowls. Environmental temperature and humidity inside the farrowing rooms were registered every 15 min. At farrowing, sows were assigned in a completely randomized design to a control diet (CON) or the CON diet supplemented with 1.0% L-arginine (ARG). A total of three gilts and two sows were fed the CON diet, whereas three gilts and three sows were fed ARG diets. Sows were fed a fixed amount of 6.0 kg/day, subdivided equally in four delivery times (0700, 1000, 1300 and 1600 h) for 21 days. At weaning, sows were slaughtered and mammary tissue samples and blood from the pudendal vein were collected. Data were analyzed considering each sow as an experimental unit. Differences were considered at P<0.05. L-arginine fed sows presented lower messenger RNA (mRNA) expression for prolactin receptor (P=0.002), angiopoietin1 (P=0.03) and receptor tyrosine kinase (P=0.01); higher mRNA expression for prostaglandin synthase 1 (P=0.01); a trend of decrease for glucocorticoid receptor (P=0.06) and IGF receptor 1 (P=0.07); and a trend (P=0.05) for an increased glutathione peroxidase mRNA expression. The angiopoietin2:angiopoietin1 mRNA ratio tended to increase (P=0.07) in ARG fed sows. L-arginine fed sows had greater (P=0.04) volumetric proportion of blood vessels and a trend of enhance (P=0.07) in the number of blood vessels per mm2. These findings show that 1.0% ARG supplementation to sows activates proliferative mechanisms, may improve mammary tissues’ angiogenesis and tended to increase mRNA expression of genes that encode antioxidant enzymes in mammary gland of sows.

Toxoplasma gondii is an intracellular protozoan parasite that causes toxoplasmosis, a prevalent infection related to abortion, ocular diseases and encephalitis in immuno-compromised individuals. In the untreatable (and life-long) chronic stage of toxoplasmosis, parasitophorous vacuoles (PVs, containing T. gondii tachyzoites) transform into tissue cysts, containing slow-dividing bradyzoite forms. While acute-stage infection with tachyzoites involves global rearrangement of the host cell cytoplasm, focused on favouring tachyzoite replication, the cytoplasmic architecture of cells infected with cysts had not been described. Here, we characterized (by fluorescence and electron microscopy) the redistribution of host cell structures around T. gondii cysts, using a T. gondii strain (EGS) with high rates of spontaneous cystogenesis in vitro. Microtubules and intermediate filaments (but not actin microfilaments) formed a ‘cage’ around the cyst, and treatment with taxol (to inhibit microtubule dynamics) favoured cystogenesis. Mitochondria, which appeared adhered to the PV membrane, were less closely associated with the cyst wall. Endoplasmic reticulum (ER) profiles were intimately associated with folds in the cyst wall membrane. However, the Golgi complex was not preferentially localized relative to the cyst, and treatment with tunicamycin or brefeldin A (to disrupt Golgi or ER function, respectively) had no significant effect on cystogenesis. Lysosomes accumulated around cysts, while early and late endosomes were more evenly distributed in the cytoplasm. The endocytosis tracer HRP (but not BSA or transferrin) reached bradyzoites after uptake by infected host cells. These results suggest that T. gondii cysts reorganize the host cell cytoplasm, which may fulfil specific requirements of the chronic stage of infection.

The present study aimed to explore the molecular factors underlying differences in Calpain/Calpastatin proteolytic system in Nellore and Angus cattle. Longissimus muscle samples were collected in Nellore (n = 6; body weight (BW) = 373 ± 37·3 kg) and Angus (n = 6; BW = 383 ± 23·9 kg) cattle at slaughter for analysis of gene and protein expression, and Calpastatin enzyme activity. Additionally, the myofibrillar fragmentation index was used to quantify the extension of proteolysis in longissimus muscle samples. A greater myofibrillar fragmentation was observed in skeletal muscle of Angus compared with Nellore cattle. Conversely, no differences were found between breeds for mRNA expression of Calpain 1 (CAPN1) and Calpastatin (CAST). Similarly, no differences were observed for the abundance of Calpain and Calpastatin proteins between skeletal muscles of Nellore and Angus cattle. Despite the lack of differences in mRNA and protein abundance, a greater activity of Calpastatin was observed in skeletal muscle of Nellore compared with Angus cattle. These data indicate that the greater proteolysis in skeletal muscle of Angus compared with Nellore cattle is mainly driven by a greater Calpastatin activity rather than Calpain or Calpastatin mRNA and protein expression.

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.

The appropriate supply of nutrients in pregnant cows has been associated with the optimal development of foetal tissues, performance of their progeny and their meat quality. The aim of this study was to evaluate supplementation effects of grazing cows in different stages of gestation on skeletal muscle development and performance of the progeny. Thereby, 27 Nellore cows were divided into three groups (n=9 for each group) and their progeny as follows: UNS, unsupplemented during gestation; MID, supplemented from 30 to 180 days of gestation; LATE, supplemented from 181 to 281 days of gestation. The percentage composition of the supplement provided for the matrices was the following: ground corn (26.25%), wheat bran (26.25%) and soya bean meal (47.5%). The supplement was formulated to contain 30% CP. Supplemented matrices received 150 kg of supplement (1 and 1.5 kg/day for cows in the MID and LATE groups, respectively). After birth, a biopsy was performed to obtain samples of skeletal muscle tissue from calves to determine number and size of muscle fibres and for messenger RNA (mRNA) expression analysis. The percentage composition of the supplement provided for the progeny was the following: ground corn grain (30%), wheat bran (30%), soya bean meal (35%) and molasses (5%). The supplement was formulated to contain 25% CP and offered in an amount of 6 g/kg BW. Performance of the progeny was monitored throughout the suckling period. Means were submitted to ANOVA and regression, and UNS, MID and LATE periods of supplementation were compared. Differences were considered at P<0.10. Birth weight, average daily gain and weaning weight of the offspring did not differ among treatments (P>0.10). Similarly, no differences were observed between calves for nutrient intake (P>0.10). However, greater subcutaneous fat thickness (P=0.006) was observed in the calves of LATE group. The ribeye area (P=0.077) was greater in calves born from supplemented compared with UNS cows. The supplementation of pregnant cows did not affect the muscle fibre size of their progeny (P=0.208). On the other hand, calves born from dams supplemented at mid-gestation had greater muscle fibre number (P=0.093) compared with calves from UNS group. Greater mRNA expression of peroxysome proliferator-activated receptor α (P=0.073) and fibroblast growth factor 2 (P=0.003) was observed in the calves born from MID cows. Although strategic supplementation did not affect the BW of offspring, it did cause changes in carcass traits, number of myofibres, and mRNA expression of a muscle hypertrophy and lipid oxidation markers in skeletal muscle of the offspring.

Among several potential animal models that can be used for adipogenic studies, Wagyu cattle is the one that presents unique molecular mechanisms underlying the deposit of substantial amounts of intramuscular fat. As such, this review is focused on current knowledge of such mechanisms related to adipose tissue deposition using Wagyu cattle as model. So abundant is the lipid accumulation in the skeletal muscles of these animals that in many cases, the muscle cross-sectional area appears more white (adipose tissue) than red (muscle fibers). This enhanced marbling accumulation is morphologically similar to that seen in numerous skeletal muscle dysfunctions, disease states and myopathies; this might indicate cross-similar mechanisms between such dysfunctions and fat deposition in Wagyu breed. Animal models can be used not only for a better understanding of fat deposition in livestock, but also as models to an increased comprehension on molecular mechanisms behind human conditions. This revision underlies some of the complex molecular processes of fat deposition in animals.

A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.

Recent studies suggest that sand can serve as a vehicle for exposure of humans to pathogens at beach sites, resulting in increased health risks. Sampling for microorganisms in sand should therefore be considered for inclusion in regulatory programmes aimed at protecting recreational beach users from infectious disease. Here, we review the literature on pathogen levels in beach sand, and their potential for affecting human health. In an effort to provide specific recommendations for sand sampling programmes, we outline published guidelines for beach monitoring programmes, which are currently focused exclusively on measuring microbial levels in water. We also provide background on spatial distribution and temporal characteristics of microbes in sand, as these factors influence sampling programmes. First steps toward establishing a sand sampling programme include identifying appropriate beach sites and use of initial sanitary assessments to refine site selection. A tiered approach is recommended for monitoring. This approach would include the analysis of samples from many sites for faecal indicator organisms and other conventional analytes, while testing for specific pathogens and unconventional indicators is reserved for high-risk sites. Given the diversity of microbes found in sand, studies are urgently needed to identify the most significant aetiological agent of disease and to relate microbial measurements in sand to human health risk.

For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.

The involvement of environmental factors in dormancy cycling is well known in temperate annual species, but it is not known how interaction between soil temperatures and humidity can modulate dormancy in perennial tropical species. In this study the effects were evaluated of substrate temperature and humidity on the modulation of the acquisition and overcoming of secondary dormancy in the buried seeds of two endemic Eriocaulaceae species from the rocky fields (campos rupestres) vegetation in south-eastern Brazil. Fresh seeds of Comanthera bisulcata and Syngonanthus verticillatus were buried and subsequently maintained at temperatures of 15, 20, 25 and 30°C, under three substrate humidity levels (boggy, humid and humid/dry). The seeds were exhumed every 3 months and tested for germination (20°C, 12 h photoperiod) and viability (tetrazolium test). The seeds of both species acquired dormancy after burial in all of the treatments. During the experimental period they demonstrated cycles of acquisition and overcoming of dormancy that were most evident in the treatments involving alterations of the substrate humidity (humid/dry regime) that coincided with the environmental conditions found naturally in the region of origin of the species. The seeds gradually lost dormancy during the dry period and re-acquired it when exposed again to humidity; dormancy would once again be overcome during the subsequent dry period. Burial promoted the acquisition of dormancy in C. bisulcata and S. verticillatus seeds; the lowest temperature tested favoured overcoming dormancy; and varying the humidity regime signalled the acquisition and the overcoming of secondary dormancy.

The aim of this study was to assess the effect of sulfamethoxazole/trimethoprim (ST) supplemented with diphenyl diselenide and sodium selenite in experimental toxoplasmosis, on oxidant/antioxidant biomarkers and cytokine levels. Eighty-four BALB/c mice were divided in seven groups: group A (negative control), and groups B to G (infected). Blood and liver samples were collected on days 4 and 20 post infection (p.i.). Levels of thiobarbituric acid (TBA) reactive substances and advanced oxidation protein products (AOPP) were assessed in liver samples. Both biomarkers were significantly increased in infected groups on day 4 p.i., while they were reduced on day 20 p.i., compared with group A. Glutathione reductase (GR) activity significantly (P<0·01) increased on day 4 p.i., in group G, compared with group A. INF-γ was significantly increased (P<0·001) in both periods, day 4 (groups B, C, F and G) and 20 p.i. (groups C, F and G). IL-10 significantly reduced (P<0·001) on day 4 p.i. in group B; however, in the same period, it was increased (P<0·001) in groups C and G, compared with group A. On day 20 p.i., IL-10 increased (P<0·001) in groups F and G. Therefore, our results highlighted that these forms of selenium, associated with the chemotherapy, were able to reduce lipid peroxidation and protein oxidation, providing a beneficial immunological balance between the production of pro- and anti-inflammatory cytokines.

Seeds can synchronize their germination and dormancy cycles to regular seasonal environmental changes. The present work sought to evaluate the in-situ longevity of the buried seeds of two species of Syngonanthus and two species of Comanthera (Eriocaulaceae) in the region of natural occurrence (Serra do Cipó Range, south-eastern Brazil), and to relate their germination responses to seasonal climatic changes. Samples were exhumed bimonthly and germination was tested under a 12-h photoperiod (30 μmol m− 2s− 1) at optimal germination temperature. The seeds of Comanthera showed high deterioration after the first year of burial, especially C. elegans, which reflects their incapacity to form viable soil seed banks. The buried seeds of C. bisulcata, S. anthemidiflorus and S. verticillatus acquired secondary dormancy during the rainy season (spring/summer, higher temperatures) which was alleviated during the subsequent dry season (autumn/winter, lower temperatures). It is concluded that C. bisulcata, S. anthemidiflorus, and S. verticillatus form seed banks of the persistent type and demonstrate consecutive cycles of germination/dormancy, accompanying annual seasonal changes for at least 2 years.

The Millimetre Astronomy Legacy Team 90 GHz (MALT90) survey aims to characterise the physical and chemical evolution of high-mass star-forming clumps. Exploiting the unique broad frequency range and on-the-fly mapping capabilities of the Australia Telescope National Facility Mopra 22 m single-dish telescope 1 , MALT90 has obtained 3′ × 3′ maps towards ~2 000 dense molecular clumps identified in the ATLASGAL 870 μm Galactic plane survey. The clumps were selected to host the early stages of high-mass star formation and to span the complete range in their evolutionary states (from prestellar, to protostellar, and on to $\mathrm{H\,{\scriptstyle {II}}}$ regions and photodissociation regions). Because MALT90 mapped 16 lines simultaneously with excellent spatial (38 arcsec) and spectral (0.11 km s−1) resolution, the data reveal a wealth of information about the clumps’ morphologies, chemistry, and kinematics. In this paper we outline the survey strategy, observing mode, data reduction procedure, and highlight some early science results. All MALT90 raw and processed data products are available to the community. With its unprecedented large sample of clumps, MALT90 is the largest survey of its type ever conducted and an excellent resource for identifying interesting candidates for high-resolution studies with ALMA.