Noonan syndrome and related disorders are a group of clinically and genetically heterogeneous conditions caused by mutations in genes of the RAS/MAPK pathway. Noonan syndrome causes multiple congenital anomalies, which are frequently accompanied by hypertrophic cardiomyopathy (HCM). We report here a Tunisian patient with a severe phenotype of Noonan syndrome including neonatal HCM, facial dysmorphism, severe failure to thrive, cutaneous abnormalities, pectus excavatum and severe stunted growth, who died in her eighth month of life. Using whole exome sequencing, we identified a de novo mutation in exon 7 of the RAF1 gene: c.776C > A (p.Ser259Tyr). This mutation affects a highly conserved serine residue, a main mediator of Raf-1 inhibition via phosphorylation. To our knowledge the c.776C > A mutation has been previously reported in only one case with prenatally diagnosed Noonan syndrome. Our study further supports the striking correlation of RAF1 mutations with HCM and highlights the clinical severity of Noonan syndrome associated with a RAF1 p.Ser259Tyr mutation.

Expression of estrus near timed artificial insemination (TAI) is associated with greater fertility, and estrus detection could improve TAI fertility or direct TAI management, although accurate estrus detection can be difficult and time-consuming using traditional methods. The aim of this study is to evaluate influence of estrus on pregnancy (artificial insemination pregnancy rates (P/AI)) and to validate an alternative method to classify estrus/heat expression using tail chalking (HEATSC) in postpartum Bos indicus cows subjected to TAI in progesterone–estrogen-based protocols. In experiment 1 (Exp. 1), cows (5491) were subjected to visual observation of estrus after progesterone device removal, before TAI, and P/AI was evaluated according to estrus and body condition score (BCS). Cows received a progesterone device and 2 mg estradiol benzoate (EB). After 8 days, the device was removed and 150 μg of d-cloprostenol and 300 IU equine chorionic gonadotrophin was given. Later, animals in Exp. 1 received 1 mg EB and TAI 44 to 48 h. In the Exp. 2 – 3830 cows using similar protocol, received different ovulation inducers: 1 mg EB (n=1624) or 1 mg estradiol cypionate (EC; n=2206) on day 8 (D8). Cows were then marked with chalk, and HEATSC evaluated at TAI on D10 (HEATSC1 – no chalk removal=no estrus expression; HEATSC2 – partial chalk removal=low estrus expression; HEATSC3 – near complete/complete chalk removal=high estrus expression). In Exp. 1, cows showing estrus presented greater P/AI (48.4% v. 40.2%, P<0.05). In Exp. 2, P/AI (HEATSC1 – 40.0%; HEATSC2 – 49.7%; HEATSC3 – 60.9%; P<0.001), and larger follicle timed artificial insemination (LFTAI) (<0.001) varied according to HEATSC. There was no difference in P/AI (P=0.41) or LFTAI (P=0.33) according to ovulation inducer. Cows with greater BCS showed greater P/AI in both experiments (P<0.05). Estrus presence and greater HEATSC improved P/AI, and EC v. EB used promoted differential estrus manifestation (cows showing HEATSC2 and HEATSC3: 79.5% with EB v. 69.98% with EC use, P<0.001), however, with similar P/AI. The use of HEATSC in B. indicus cows subjected to TAI is useful to identify cows with greater estrus expression and consequently improved pregnancy rates in TAI, allowing the cows with low HEATSC to be targeted for additional treatments aimed at improving P/AI.

Expression of estrus (EST) near the time of fixed-time artificial insemination (FTAI) increases pregnancy success in beef females. This outcome has been associated with improved pregnancy establishment and maintenance, although research is still warranted to validate this theory. Hence, this experiment compared ovarian, uterine and conceptus factors associated with pregnancy establishment in Bos indicus beef cows according to estrous expression during a FTAI protocol. One hundred lactating multiparous Nelore cows received a 2 mg injection of estradiol benzoate and an intravaginal progesterone (P4) releasing device on day −11, a 12.5 mg injection of prostaglandin F2α on day −4, P4 device removal in addition to 0.6 mg injection of estradiol cypionate and 300 IU injection of equine chorionic gonadotropin on day −2, and FTAI on day 0. An estrous detection patch was attached to the tailhead of each cow on day −2, and estrous expression was defined as removal of >50% of the rub-off coating from the patch at FTAI. Overall, 39 cows expressed EST, 55 did not express EST (NOEST), and six cows lost their patch and were discarded from the experiment. Ovarian ultrasonography was performed at FTAI, and on days 7 and 15 of the experiment. Blood samples were also collected on days 7 and 15. Only cows without a corpus luteum (CL) on day 0, and with a CL on days 7 and 15 remained in the experiment (EST, n=36; NOEST, n=48). On day 15, cows were randomly selected within each group (EST, n=29; NOEST, n=30) for conceptus collection via transcervical flushing, followed by endometrial biopsy in the uterine horn ipsilateral to the CL. Within cows not assigned to conceptus collection, blood samples were collected for whole blood RNA extraction (day 20) and pregnancy status was verified by transrectal ultrasonography (day 30). Diameter of dominant follicle on day 0 and plasma P4 concentrations on day 7 were greater (P⩽0.02) in EST v. NOEST cows. Conceptus length and messenger RNA (mRNA) expression of prostaglandin E synthase and interferon-tau were greater (P⩽0.04) in EST v. NOEST cows. Moreover, EST cows diagnosed as pregnant on day 30 had greater (P<0.01) blood mRNA expression of myxovirus resistance 2 on day 20 compared with NOEST. In summary, estrous expression near the time of FTAI enhanced pregnancy establishment factors in B. indicus cows, including conceptus development and mRNA expression of interferon-tau.

Infection with Eimeria sp. results in the activation of multiple facets of the host immune system; the use of phytogenics can modulate the inflammatory response and improve the performance of the challenged animal. The aim of this study was to evaluate the effect of a commercial blend of cashew nut shell liquid (CNSL) and castor oil on the immune response of broilers challenged with coccidiosis. A total of 864 one-day-old male chicks (Cobb 500) were randomly distributed into six treatment groups (8 pens/treatment and 18 chicks/pen) in a three-by-two factorial design with three additives: control (non-additive), 100 ppm of monensin or 0.15% CNSL–castor oil. Challenge status was determined twice at 14 days of age. Unchallenged birds were inoculated by gavage with oocysts sporulated with Eimeria tenella, Eimeria acervulina and Eimeria maxima. Although the positive control (non-additive and challenged) and CNSL–castor oil treatment groups exhibited similar variation in weight gain (ΔBWG) compared to unchallenged birds fed without additives, the variation observed in birds fed diets containing CNSL–castor oil was associated with a higher maintenance requirement and not feed efficiency. In the second week after infection, ΔBWG of the CNSL–castor oil treatment group did not significantly change compared to the other treatment groups. At days 7 and 14 post-challenge, there was a higher excretion of oocysts in the control group, whereas the CNSL–castor oil and monensin groups did not differ. The CNSL–castor oil group exhibited increased gene expression of interferon (IFN), interleukin 6 (IL-6) and tumor necrosis factor (TNF), while the control group exhibited increased expression of cyclooxygenase (COX) and IL-1. The heterophils/lymphocyte ratio was low for the monensin treatment group. The unchallenged birds that received monensin treatment presented higher gene expression of IFN, COX and IL-1 compared to the other treatments, while the CNSL–castor oil group exhibited reduced gene expression, except for TNF. The commercial blend of cashew nut liquid and castor oil modulated the inflammatory response against Eimeria spp. In the absence of the parasite, there was no stimulation of genes involved in the inflammatory response, demonstrating that the blend is an effective tool in specifically modulating the immune system of birds afflicted with coccidiosis.

Force-feeding was considered as a traditional high-efficiency approach to improve growth performance and accelerate fat deposition of Pekin ducks. However, force-feeding is a serious violation of international advocacy on animal welfare, because it can induce serious injuries to animals, such as damages to the digestive tract, effects on immunity and even severe oxidative stress. Therefore, it is urgent to stop force-feeding. The aim of this study was to determine the effects of force feeding on immune function, digestive function and oxidative stress in the mucosa of duodenum and jejunum of Pekin ducks. A total of 500 ducks were randomly divided into two groups. The control group was allowed to feed freely on a basal diet. The experimental group was force-fed by inserting a plastic feeding tube 8 to 10 inches long down the esophagus for 6 days. Compared with the control group, there was a significant (P<0.05) increase in serum diamine oxidase, d-lactic acid, endotoxin and corticosterone levels in the force-feeding group. The crypt depth in duodenum and jejunum showed significant differences (P<0.05) between the two groups and the intestinal villus epithelium cell was severely damaged in force-feeding group. Similarly, the activities of digestive enzymes as well as the levels of immune function in the duodenal and jejunal mucosa in the force-feeding group were significantly higher than the control group (P<0.05). However, there was a significant decrease in the superoxide dismutase, glutathione peroxidase and catalase levels with a marked increase in malondialdehyde level in duodenal and jejunal mucosa (P<0.05). In summary, at the end of the fattening period with force-feeding for 6 days, Pekin ducks experienced an adverse effect on the integrity of their duodenal and jejunal mucosa epithelium cell as well as their immune function and antioxidant capacity of Pekin ducks but also had improvement in digestive enzyme activities.

The Mangalitza pig breed has suffered strong population reductions due to competition with more productive cosmopolitan breeds. In the current work, we aimed to investigate the effects of this sustained demographic recession on the genomic diversity of Mangalitza pigs. By using the Porcine Single Nucleotid Polymorphism BeadChip, we have characterized the genome-wide diversity of 350 individuals including 45 Red Mangalitza (number of samples; n=20 from Hungary and n=25 from Romania), 37 Blond Mangalitza, 26 Swallow-belly Mangalitza, 48 Blond Mangalitza × Duroc crossbreds, 5 Bazna swine, 143 pigs from the Hampshire, Duroc, Landrace, Large White and Pietrain breeds and 46 wild boars from Romania (n=18) and Hungary (n=28). Performance of a multidimensional scaling plot showed that Landrace, Large White and Pietrain pigs clustered independently from Mangalitza pigs and Romanian and Hungarian wild boars. The number and total length of ROH (runs of homozygosity), as well as FROH coefficients (proportion of the autosomal genome covered ROH) did not show major differences between Mangalitza pigs and other wild and domestic pig populations. However, Romanian and Hungarian Red Mangalitza pigs displayed an increased frequency of very long ROH (>30 Mb) when compared with other porcine breeds. These results indicate that Red Mangalitza pigs underwent recent and strong inbreeding probably as a consequence of severe reductions in census size.

Sodium and chloride are the key factors maintaining normal osmotic pressure (OSM) and volume of the extracellular fluid, and influencing the acid–base balance of body fluids. The experiment was conducted to investigate the effects of dietary Na+ and Cl− level on growth performance, excreta moisture, blood biochemical parameters, intestinal Na+–glucose transporter 1 (SGLT1) messenger RNA (mRNA), and Na+–H+ exchanger 2 (NHE2) mRNA, and to estimate the optimal dietary sodium and chlorine level for yellow-feathered chickens from 22 to 42days. A total of 900 22-day-old Lingnan yellow-feathered male chickens were randomly allotted to five treatments, each of which included six replicates of 30 chickens per floor pen. The basal control diet was based on corn and soybean meal (without added NaCl and NaHCO3). Treatments 2 to 5 consisted of the basal diet supplemented with equal weights of Na+ and Cl−, constituting 0.1%, 0.2%, 0.3% and 0.4% of the diets. Supplemental dietary Na+ and Cl− improved the growth performance (P<0.05). Average daily gain (ADG) showed a quadratic broken-line regression to increasing dietary Na+ and Cl− (R2=0.979, P<0.001), and reached a plateau at 0.1%. Supplemental Na+ and Cl− increased (P<0.05) serum Na+ and OSM in serum and showed a quadratic broken-line regression (R2=0.997, P=0.004) at 0.11%. However, supplemental Na+ and Cl− decreased (P<0.05) serum levels of K+, glucose (GLU) and triglyceride. Higher levels of Na+and Cl− decreased duodenal NHE2 transcripts (P<0.05), but had no effect on ileal SGLT1 transcripts. The activity of Na+ /K+-ATPase in the duodenum decreased (P<0.05) with higher levels of dietary Na+ and Cl−. In conclusion, the optimal dietary Na+ and Cl− requirements for yellow-feathered chickens in the grower phase, from 22 to 42 days of age, to optimize ADG, serum Na+, OSM, K+ and GLU were 0.10%, 0.11%, 0.11%,0.17% and 0.16%, respectively, by regression analysis.

Flystrike costs the Australian industry $173 to 280 M per annum and 70% to 80% of Merino lambs are currently mulesed to reduce the risk of flystrike. To alleviate welfare concerns there has been widespread adoption of analgesics to mitigate the pain associated with mulesing. The objective of this experiment was to determine the effectiveness of Tri-Solfen® and meloxicam (Metacam® 20) at reducing pain-related behavioural responses to mulesing in Merino lambs. One hundred and forty Merino lambs were allocated to one of seven treatment groups: (1) non-mulesed (Control); (2) mulesed with no pain relief; (3) subcutaneous (s.c.) meloxicam administered 15 min before mulesing; (4) Tri-Solfen® administered at time of mulesing; (5) Tri-Solfen® and saline injection (s.c.) 15 min before mulesing; (6) Tri-Solfen® and meloxicam (s.c.) 15 min before mulesing; and (7) meloxicam (s.c.) at time the of mulesing. Behavioural responses such as standing, walking and lying were measured every 15 min for 6 h on the day of marking and for up to 2 h for 4 days thereafter. Standing (hunched v. normal) and walking (stiff v. normal) behaviours were then categorised into pain- and normal-related behaviours while lying remained in its own category. Mulesed lambs with no pain relief displayed significantly more pain-related behaviours than Control lambs during the 6 h post-mulesing (1.22 v. 0.22 out of a total score of 3; RSD=1.15). Lambs that received a combination of pain relief displayed significantly less pain-related behaviour than mulesed lambs with no pain relief on the day of mulesing (0.85 v. 1.22 out of a total score of 3; RSD=1.15). Administration of meloxicam or Tri-Solfen® on their own had minimal if any significant effect on pain-related behaviours on the day of mulesing. The results of this experiment support the use of pain-related behaviours to measure the efficacy of analgesics and the use of multimodal analgesia during mulesing of lambs.

In terms of animal welfare, farming systems of dairy cows are perceived positively by consumers when compared to pigs or poultry. A main reason is that the majority of consumers associate dairy farming with pasture, which in turn they relate with benefits for animal health and welfare. However, holistic scientific assessments of the effects of pasturing on animal welfare are rare. Hence, it was the aim to study the animal welfare level in 61 German loose housing dairy farms by using the measures of the Welfare Quality® protocol for dairy cattle (WQP). Data were collected twice per farm at the end of the pasture season (July to October) and approximately 6 months later at the end of the barn season (December to April). Farms were classified based on the duration cows had access to pasture per day during the pasture season: group 1 (G1)>10 h; group 2 (G2) 6 to 10 h; group 3 (G3)<6 h and group 4 (G4) without pasture access. The average herd size was 129 Holstein-Friesian or Red-Holstein cows (range 58 to 527). In addition to WQP data, performance data were gathered from routine herd data recordings. The indicators were aggregated to criteria applying the scoring system of the WQP. G4 received lower scores at the first than at the second visit for the criterion absence of hunger, while there were no differences between visits in the other groups (P=0.58 – group×farm visit effect). All pasturing groups were scored better at the end of the pasture season than G4 for the criterion comfort around resting (P<0.01). Compared with G1 for both farm visits and G2 for the end of the barn season, G4 reached inferior scores for the criterion absence of injuries, including indicators such as hairless patches, lesions, and swellings and lameness. At both assessments G2 was scored higher than the other groups for the criterion absence of diseases (P=0.04). In conclusion, pasture access had positive effects only on selected welfare indicators, however, these effects were not maintained throughout the barn season.

To evaluate how rearing programmes could affect resources allocation and reproductive performance of primiparous rabbit females, a total of 118 rabbit females were used to evaluate the effects of five rearing feeding programmes on their performance from 1st to 2nd parturition: CAL, fed ad libitum C diet (11.0 MJ digestible energy (DE), 114 g digestible protein (DP) and 358 g NDF/kg dry matter (DM) until 1st parturition; CR, fed ad libitum with C diet until 12 weeks of age and then C diet restricted (140 g/day) until 1st parturition; F, fed ad libitum with F diet (8.7 MJ DE, 88 g DP and 476 NDF/kg DM) until 1st parturition; FC, fed with F diet ad libitum until 16 weeks of age, and C diet ad libitum until 1st parturition; FCF, fed with F diet ad libitum until 16 weeks of age, then C diet ad libitum until 20 weeks and then F diet ad libitum until 1st parturition. From 1st parturition, C diet was ad libitum offered to all the experimental groups until 2nd parturition. CAL females presented lower feed intake than females of F, FC and FCF groups in the 1st week of lactation (on av. −16.6%; P<0.05). During 1st lactation, the perirenal fat thickness change in CAL females was not different from 0 (+0.02 mm), while in the other four groups it increased (on av. +0.44 mm; P<0.05). Plasma of females fed with F diet during rearing (F, FC and FCF) had lower non-esterified fatty acids content than those exclusively fed with C diet (–0.088 and –0.072 mmol/l compared to CAL and CR, respectively; P<0.05). FCF litters had higher weight than F litters at day 21 of lactation (+247 g; P<0.05), but FCF litter had significantly lower weight than FC litters at weaning (+170 g; P<0.05). CR females had the shortest average interval between the 1st and 2nd parturition (49 days) and FCF females the longest (+ 9 days compared to CR; P<0.05). At 2nd parturition, liveborn litters of F females were larger and heavier than litters of FCF females (+2.22 kits and +138 g; P<0.05), probably due to the lower mortality at birth of F litters (–16.5 percentage points; P<0.05). In conclusion, rearing females on fibrous diets seems to increase the ability of primiparous rabbit females to obtain resources, especially at the onset of lactation.

The use of tail chalk and estrus/heat expression scores (HEATSC) evaluation is instrumental in identifying cows with greater estrus expression and greater artificial insemination pregnancy rates (P/AI) in cows submitted to timed artificial insemination (TAI), and cows with low or no estrus expression present lower P/AI. It was intended in this study to improve the pregnancy rates in TAI for Bos indicus beef cows, and gonadotrophin-releasing hormone (GnRH) injection was hypothesized to increase pregnancy rates in a TAI program for cows submitted to progesterone–estradiol-based protocols with low or no estrus expression, evaluated by HEATSC. Cows (n= 2284) received a progesterone device and 2 mg estradiol benzoate, after 8 days the device was removed and 1 mg estradiol cypionate, 150 μg of d-cloprostenol and 300 IU equine chorionic gonadotropin was administered. All cows were marked with chalk and HEATSC evaluated (scales 1 to 3) at TAI performed on day 10. Animals with HEATSC1 and HEATSC2 (n= 937) received 100 μg de gonadorelin (GNRH group; n= 470), or 1 ml saline (Control group; n= 467), and cows with HEATSC3 (named HEAT group; n= 1347) received no additional treatment. The larger dominant follicle, evaluated on day 8and at TAI (day 10), was greater in HEAT group (P= 0.0145 and P <0.001, respectively). Corpus luteum (CL) area and progesterone concentration was evaluated on day 17, and CL area was larger in HEAT group, intermediary in Control and lower in GnRH group (Control= 2.68 cm2, GnRH= 2.37 cm2, HEAT group= 3.07 cm2, P <0.001). Greater progesterone concentrations were found in HEAT group than in Control and GnRH groups (Control= 4.74 ng/ml, GnRH= 4.29 ng/ml, HEAT group= 6.08 ng/ml, P<0.001). There was a difference in ovulation rate, greater in HEAT group than GnRH and Control groups (Control= 72.5%; GnRH= 81.25%; HEAT group= 90.71%; P= 0.0024). Artificial insemination pregnancy rates was greater in HEAT group (57.09% (769/1347) than in Control and GNRH groups, with positive effect of GnRH injection at the time of TAI in P/AI (Control= 36.18% (169/467), GnRH= 45.95% (216/470); P<0.0001). In conclusion, GnRH application in cows with low HEATSC (1 and 2) is a simple strategy, requiring no changes in TAI management to increase pregnancy rates in postpartum beef cows submitted to progesterone–estradiol-based TAI protocols, without reaching, however, the pregnancy rates of cows that demonstrate high estrus expression at the TAI.

Nowadays, there is much legislation in the world devoted to restrict the use of synthetic antibiotics in the poultry industry, which could reduce performance rate and production profits. Various phyto-biotic growth promoters have been proposed to serve as antibiotic alternatives with emphasis on plant extracts and essential oils. This study was conducted to assess the impacts of using the oregano essential oil (OEO) (comprised of 5% thymol and 65% carvacrol) and Enviva essential oil (EEO) (4.5% cinnamaldehyde and 13.5% thymol) as phytobiotic feed additives (PFA) on growth performance, cecal microbiota and serum biochemicals of growing ducks. In total, 800 11-day-old ducklings, housed in 20 floor pens, were allotted randomly into five dietary treatments: (i) A basal diet (BD) (control), (ii.) BD+50 mg EEO/kg, (iii.) BD+100 mg EEO/kg, (iv.) BD+150 mg OEO/kg and (v.) BD+300 mg OEO/kg diet. The growth performance traits were studied between 11 and 42 days of age. At the experiment end, 40 ducks were slaughtered (eight/ treatment) and cecal digesta and blood samples were collected to estimate the cecal bacterial populations and serum blood biochemicals. The results indicated that the tested levels of OEO and EEO did not display any significant effect (P>0.05) on the duck’s final BW, BW gain, growth rate, feed intake, feed conversion ratio or survivability rate. Besides, the different levels of EEO and OEO decreased the cecal populations of Coliforms (P<0.01), total aerobes (P<0.01) and lactose-negative Enterobacteria (P<0.05) in comparison with those of the control group. Finally, the tested EEO and OEO levels did not show any significant effect on the serum variables; in terms of total protein, albumin, globulin, total cholesterol, triglycerides, alanine aminotransferase and aspartate aminotransferase. In conclusion, the antimicrobial effect of the OEO and EEO against the cecal microbiota has been proven, while they did not display significant effects on the growth performance or blood variables of growing ducks.

GenomeAsia100K is a human genome project based at Nanyang Technological University in Singapore that aims to sequence one hundred thousand Asian genomes in an effort that addresses an ethnic bias towards Western populations in previous genomic research. GenomeAsia100K consists of a team of bioinformaticians, statisticians and population geneticists, and was initiated by the Nanyang Technological University in collaboration with industrial partners MedGenome (an Indian R&D company specializing in genomic data) and the California Biotech company Genentech. The GenomeAsia100K project is amongst the most ambitious precision medicine projects to date but it is not clear how the project will challenge or reshape understandings of ethnic and racial differences in Asian populations. Ian McGonigle, a scientist and cultural anthropologist, sat down with geneticist Stephan C. Schuster, the scientific chairman of GenomeAsia100K, to discuss the project and the implications of genomics for social identity in the 21st century.

The aim of this study was to explore lameness and the associations between lameness and health/production measures of animal welfare in commercial broiler production, using the Welfare Quality® protocol for broilers. A total of 50 flocks were included in the sample and farm visits were conducted for lameness scoring at a mean age of 28.9 days. The percentage of animals (n=7500) in the six different gait score (GS) categories were GS0: 2.53%, GS1: 44.19%, GS2: 33.84%, GS3: 16.32%, GS4: 2.36% and GS5: 0.53%. Production and other welfare data were collected for each flock after slaughter. Higher gait scores were associated with increased hock burn score (P<0.02), increased footpad dermatitis score (P<0.01), reduced bird cleanliness score (P<0.01) and peat litter (P<0.01). Although not statistically significant, there was a tendency for increased flock gait score being associated with wet litter (P=0.07). In addition, condemnations at postmortem inspection were associated with increasing gait scores (P<0.05), indicating that at least a portion of the lameness cases display pathological changes on the carcasses. In conclusion, 19%of the birds showed moderate-to-severe lameness, which was associated with several production or health and welfare observations including feather cleanliness and condemnations as unfit for human consumption at slaughter. Although stocking density and growth rate are already known key factors for lameness, associations of lameness with hock burns, footpad dermatitis and cleanliness of the birds suggest that a suboptimal physical environment (e.g. litter- and air quality) may be detrimental to leg health. Further studies are needed to explore these associations in more detail.