Phenotypic correlations between feed efficiency, growth, and meat quality of slow-growing chickens.

1. Korat (KR) chicken is a new meat-type chicken breed established with the purpose of developing Small and Micro Community Enterprise Production. This slow-growing chicken has been recognised for its good texture and flavour, but its low feed efficiency is associated with high cost of production which can hamper the development of local production. This has highlighted the importance of studying the trade-off between feed efficiency and meat quality in KR chicken.2. This study investigated the phenotypic correlations between feed efficiency, growth performance, and meat quality in KR chicken. Individual body weight and feed intake were recorded weekly for 75 male KR chickens for the calculation of feed conversion ratio (FCR) and residual feed intake (RFI). The growth curve was modelled by Gompertz function and meat quality evaluated at 10 weeks of age, through the measurement of pH (pHu), water-holding capacity (WHC) and drip loss (DL) in breast and thigh muscle.3. Faster growth rate at young age appeared favourable, regarding feed efficiency, since a moderate negative correlation was found between FCR and initial growth rate. Chickens with a higher initial growth and maturation rates were characterised by lower water-holding capacity in meat. This was not associated with acidic meat, since a higher speed of growth (especially in the first weeks) was positively associated with final pH in breast meat. Relationships between RFI and meat quality traits appeared to be weak. While better FCR could be achieved by increased initial growth rate, this seemed to negatively impact water-holding capacity of the meat.4. RFI appeared as an interesting alternative as a compromise between FCR and meat quality.

Risk of relapse after anti-PD1 discontinuation in patients with Hodgkin lymphoma.

INTRODUCTION: Patients with relapsed/refractory Hodgkin lymphoma (R/R HL) experience high response rates upon anti-PD1 therapy. In these patients, the optimal duration of treatment and the risk of relapse after anti-PD1 discontinuation are unknown. METHODS: We retrospectively analyzed patients with R/R HL who responded to anti-PD1 monotherapy and discontinued the treatment either because of unacceptable toxicity or prolonged remission. A machine learning algorithm based on 17 candidate variables was trained and validated to predict progression-free survival (PFS) landmarked at the time of discontinuation of anti-PD1 therapy. RESULTS: Forty patients from 14 centers were randomly assigned to training (n = 25) and validation (n = 15) sets. At the time of anti-PD1 discontinuation, patients had received treatment for a median duration of 11.2 (range, 0-time to best response was not statistically significant in discriminating patients with PFS lesser or greater than 12 months). Considering PFS status as a binary variable (alive or dead) at a specific time point (12 months) is convenient, intuitive and allows for comparing the value of potential predicting variables in these two groups of patients. Nonetheless, this approach has two drawbacks: first, it binarizes outcome; second, it excludes patients alive with a time to last follow up lesser 12 months. Therefore, it is less powerful to demonstrate statistically significant association with PFS even if it exists 5 months. Patients discontinued anti-PD1 treatment either because of prolonged remission (N = 27, 67.5%) or unacceptable toxicity (N = 13, 32.5%). Most patients were in CR (N = 35, 87.5%) at the time of anti-PD1 discontinuation. In the training set, the machine learning algorithm identified that the most important variables to predict PFS were patients' age, time to best response, and presence or absence of CR. The performance observed in the training set was validated in the validation set. CONCLUSION: In this pilot, proof of concept study using a machine learning algorithm, we identified biomarkers capable of predicting the risk of relapse after anti-PD1 discontinuation (age, time to best response, quality of response). Once confirmed, these simple biomarkers will represent useful tools to guide the management of these patients.

Multi-tissue transcriptomic study reveals the main role of liver in the chicken adaptive response to a switch in dietary energy source through the transcriptional regulation of lipogenesis.

BACKGROUND: Because the cost of cereals is unstable and represents a large part of production charges for meat-type chicken, there is an urge to formulate alternative diets from more cost-effective feedstuff. We have recently shown that meat-type chicken source is prone to adapt to dietary starch substitution with fat and fiber. The aim of this study was to better understand the molecular mechanisms of this adaptation to changes in dietary energy sources through the fine characterization of transcriptomic changes occurring in three major metabolic tissues - liver, adipose tissue and muscle - as well as in circulating blood cells. RESULTS: We revealed the fine-tuned regulation of many hepatic genes encoding key enzymes driving glycogenesis and de novo fatty acid synthesis pathways and of some genes participating in oxidation. Among the genes expressed upon consumption of a high-fat, high-fiber diet, we highlighted CPT1A, which encodes a key enzyme in the regulation of fatty acid oxidation. Conversely, the repression of lipogenic genes by the high-fat diet was clearly associated with the down-regulation of SREBF1 transcripts but was not associated with the transcript regulation of MLXIPL and NR1H3, which are both transcription factors. This result suggests a pivotal role for SREBF1 in lipogenesis regulation in response to a decrease in dietary starch and an increase in dietary PUFA. Other prospective regulators of de novo hepatic lipogenesis were suggested, such as PPARD, JUN, TADA2A and KAT2B, the last two genes belonging to the lysine acetyl transferase (KAT) complex family regulating histone and non-histone protein acetylation. Hepatic glycogenic genes were also down-regulated in chickens fed a high-fat, high-fiber diet compared to those in chickens fed a starch-based diet. No significant dietary-associated variations in gene expression profiles was observed in the other studied tissues, suggesting that the liver mainly contributed to the adaptation of birds to changes in energy source and nutrients in their diets, at least at the transcriptional level. Moreover, we showed that PUFA deposition observed in the different tissues may not rely on transcriptional changes. CONCLUSION: We showed the major role of the liver, at the gene expression level, in the adaptive response of chicken to dietary starch substitution with fat and fiber.

KIRREL is differentially expressed in adipose tissue from 'fertil+' and 'fertil-' cows: in vitro role in ovary?

We have previously shown that dairy cows carrying the 'fertil-' haplotype for one quantitative trait locus affecting female fertility located on the bovine chromosome three (QTL-F-Fert-BTA3) have a significantly lower conception rate and body weight after calving than cows carrying the 'fertil+' haplotype. Here, we compared by Tiling Array the expression of genes included in the QTL-F-Fert-BTA3 in 'fertil+' and 'fertil-' adipose tissue one week after calving when plasma non-esterified fatty acid concentrations were greater in 'fertil-' animals. We observed that thirty-one genes were overexpressed whereas twelve were under-expressed in 'fertil+' as compared to 'fertil-' cows (P < 0.05). By quantitative PCR and immunoblot we confirmed that adipose tissue KIRREL mRNA and protein were significantly greater expressed in 'fertil+' than in 'fertil-'. KIRREL mRNA is abundant in bovine kidney, adipose tissue, pituitary, and ovary and detectable in hypothalamus and mammary gland. Its expression (mRNA and protein) is greater in kidney of 'fertil+' than 'fertil-' cows (P < 0.05). KIRREL (mRNA and protein) is also present in the different ovarian cells with a greater expression in granulosa cells of 'fertil+' than 'fertil-' cows. In cultured granulosa cells, recombinant KIRREL halved steroid secretion in basal state (P < 0.05). It also decreased cell proliferation (P < 0.05) and in vitro oocyte maturation (P < 0.05). These results were associated to a rapid increase in MAPK1/3 and MAPK14 phosphorylation in granulosa cells and to a decrease in MAPK1/3 phosphorylation in oocyte. Thus, KIRREL could be a potential metabolic messenger linking body composition and fertility.

Possible roles of parathyroid hormone, 1.25(OH)2D3, and fibroblast growth factor 23 on genes controlling calcium metabolism across different tissues of the laying hen.

This study provides an integrative description of candidate gene expression across tissues involved in calcium (Ca) metabolism during the egg laying cycle, using the well-defined model of Ca supply as fine or coarse particles of calcium carbonate (CaCO3). Plasma and tissue samples were collected from hens at the peak of laying at 0 to 1, 9 to 10, and 18 to 19 h postovulation (PO). After mRNA preparation from the parathyroid gland, medullary bone, liver, kidney, duodenum, and jejunum, gene expressions were quantified using RT-qPCR. The highest levels of parathyroid hormone (PTH) mRNA in the parathyroid gland (P < 0.05), and of the active form of vitamin D3 1.25(OH)2D3 in the plasma (P < 0.01) were observed at 18 to 19 h PO. During this active phase of eggshell formation, bone resorption was attested to high levels of plasma inorganic phosphorus (iP) and the receptor activation of nuclear factor-κB expression in the bone (P < 0.001 and P < 0.05, respectively). At this stage, 5 genes of the transcellular and the paracellular Ca absorption pathways in the intestine (P < 0.05) and the Ca channel transient receptor potential cation channel subfamily V member 5 (P < 0.05), involved in its reabsorption in the kidney, were overexpressed. At 0 to 1 h PO during the subsequent daylight period, 2 candidates of the transcellular and the paracellular Ca pathways (P < 0.05) remained at high levels in the intestine, while calbindin D 28K expression was the highest in the kidney (P < 0.05). As PTH mRNA and 1.25(OH)2D3 were low, bone accretion was likely active at this stage. The phosphaturic hormone fibroblast growth factor 23 (FGF23) was overexpressed at 18 to 19 h PO (P < 0.05) in the bone when plasma iP was high, which suggested a role in the subsequent reduction of P reabsorption in the kidney, as attested to the decreased expression of P cotransporters, leading to iP clearance from the plasma at 0 to 1 h PO (P < 0.05). The low levels of 1.25(OH)2D3 at this stage coincided with increased expression of the 24-hydroxylase gene in the kidney (P < 0.05). In hens fed fine particles of CaCO3, higher plasma levels of 1,25(OH)2D3 and higher expression of several genes involved in bone turnover reflected a stronger challenge to Ca homeostasis. Altogether, these data support the hypothesis that FGF23 could drive vitamin D metabolism in the laying hen, as previously documented in other species and explain the tight link between P and Ca metabolisms.

Mapping of QTL for chicken body weight, carcass composition, and meat quality traits in a slow-growing line.

Slow-growing chicken lines are valuable genetic resources for the development of well-perceived alternative free-range production. While there is no constraint on increasing growth rate, breeding programs have to evolve in order to include new traits improving the positioning of such lines in the growing market for parts and processed products. In this study, we used dense genotyping to fine map QTL for chicken growth, body composition, and meat quality traits in view of developing new tools for selection of a slow-growing line. The dataset included a total of 836 birds (10 sires, 87 dams, 739 descendants) and 40,203 SNP. QTL for the 15 traits analyzed were detected by 3 different methods, i.e., linkage and linkage disequilibrium haplotype-based analysis (LDLA), family-based single marker association (FASTA), and Bayesian multi-marker regression (Bayes Cπ). After filtering for QTL redundancy, we found 16, 16, and 9 QTL when using the FASTA, LDLA, and Bayes Cπ methods, respectively, with a threshold of 2.49 × 10-5 for FASTA and LDLA, and a Bayes factor of 150 for the Bayes Cπ analysis. They comprised 17 QTL for body weight, 9 QTL for body composition, and 15 QTL for breast meat quality or behavior at slaughter. The 3 methods agreed in the detection of highly significant QTL such as that detected on GGA24 for body weight at 3, 6, and 9 wk, and the 2 QTL detected on GGA17 and GGA18 for breast meat yield. Several significant QTL were also detected for the different components of breast meat quality. This study provided new locations for investigation in order to improve our understanding of the genetic architecture of growth, carcass composition, and meat quality in the chicken and to develop molecular tools for the selection of these traits in a slow-growing line.

Cyclic variations in incubation conditions induce adaptive responses to later heat exposure in chickens: a review.

Selection programs have enabled broiler chickens to gain muscle mass without similar enlargement of the cardiovascular and respiratory systems that are essential for thermoregulatory efficiency. Meat-type chickens cope with high ambient temperature by reducing feed intake and growth during chronic and moderate heat exposure. In case of acute heat exposure, a dramatic increase in morbidity and mortality can occur. In order to alleviate heat stress in the long term, research has recently focused on early thermal manipulation. Aimed at stimulation of long-term thermotolerance, the thermal manipulation of embryos is a method based on fine tuning of incubation conditions, taking into account the level and duration of increases in temperature and relative humidity during a critical period of embryogenesis. The consequences of thermal manipulation on the performance and meat quality of broiler chickens have been explored to ensure the potential application of this strategy. The physiological basis of the method is the induction of epigenetic and metabolic mechanisms that control body temperature in the long term. Early thermal manipulation can enhance poultry resistance to environmental changes without much effect on growth performance. This review presents the main strategies of early heat exposure and the physiological concepts on which these methods were based. The cellular mechanisms potentially underlying the adaptive response are discussed as well as the potential interest of thermal manipulation of embryos for poultry production.

Comparative genomic hybridization analysis of Enterococcus faecalis: identification of genes absent from food strains.

Enterococcus faecalis, a member of the natural microbiota of animal and human intestinal tracts, is also present as a natural contaminant in a variety of fermented foods. Over the last decade, E. faecalis has emerged as a major cause of nosocomial infections. We investigated the genetic diversity in 30 clinical and food isolates, including strains V583 and MMH594, in order to determine whether clinical and food isolates could be distinguished. Data were obtained using comparative genomic hybridization and specific PCR with a total of 202 probes of E. faecalis, selected using the available V583 genome sequence and part of the MMH594 pathogenicity island. The cognate genes encoded mainly exported proteins. Hybridization data were analyzed by a two-component mixture model that estimates the probability of any given gene to be either present or absent in the strains. A total of 78 genes were found to be variable, as they were absent in at least one isolate. Most of the variable genes were clustered in regions that, in the published V583 sequence, related to prophages or mobile genetic elements. The variable genes were distributed in three main groups: (i) genes equally distributed between clinical and dairy food isolates, (ii) genes absent from dairy food-related isolates, and (iii) genes present in MMH594 and V583 strains only. Further analysis of the distribution of the last gene group in 70 other isolates confirmed that six of the probed genes were always absent in dairy food-related isolates, whereas they were detected in clinical and/or commensal isolates. Two of them corresponded to prophages that were not detected in the cognate isolates, thus possibly extending the number of genes absent from dairy food isolates. Genes specifically detected in clinical isolates may prove valuable for the development of new risk assessment markers for food safety studies and for identification of new factors that may contribute to host colonization or infection.