A genome-wide association study on androstenone levels in pigs reveals a cluster of candidate genes on chromosome 6

<p>Abstract</p> <p>Background</p> <p>In many countries, male piglets are castrated shortly after birth because a proportion of un-castrated male pigs produce meat with an unpleasant flavour and odour. Main compounds of boar taint are androstenone and skatole. The aim of this high-density genome-wide association study was to identify single nucleotide polymorphisms (SNPs) associated with androstenone levels in a commercial sire line of pigs. The identification of major genetic effects causing boar taint would accelerate the reduction of boar taint through breeding to finally eliminate the need for castration.</p> <p>Results</p> <p>The Illumina Porcine 60K+SNP Beadchip was genotyped on 987 pigs divergent for androstenone concentration from a commercial Duroc-based sire line. The association analysis with 47,897 SNPs revealed that androstenone levels in fat tissue were significantly affected by 37 SNPs on pig chromosomes SSC1 and SSC6. Among them, the 5 most significant SNPs explained together 13.7% of the genetic variance in androstenone. On SSC6, a larger region of 10 Mb was shown to be associated with androstenone covering several candidate genes potentially involved in the synthesis and metabolism of androgens. Besides known candidate genes, such as cytochrome P450 A19 (<it>CYP2A19</it>), sulfotransferases <it>SULT2A1</it>, and <it>SULT2B1</it>, also new members of the cytochrome P450 <it>CYP2 </it>gene subfamilies and of the hydroxysteroid-dehydrogenases (<it>HSD17B14</it>) were found. In addition, the gene encoding the ß-chain of the luteinizing hormone (<it>LHB</it>) which induces steroid synthesis in the Leydig cells of the testis at onset of puberty maps to this area on SSC6. Interestingly, the gene encoding the α-chain of LH is also located in one of the highly significant areas on SSC1.</p> <p>Conclusions</p> <p>This study reveals several areas of the genome at high resolution responsible for variation of androstenone levels in intact boars. Major genetic factors on SSC1 and SSC6 showing moderate to large effects on androstenone concentration were identified in this commercial breeding line of pigs. Known and new candidate genes cluster especially on SSC6. For one of the most significant SNP variants, the difference in the proportion of animals surpassing the threshold of consumer acceptance between the two homozygous genotypes was as much as 15.6%.</p

The distal end of porcine chromosome 6p is involved in the regulation of skatole levels in boars

<p>Abstract</p> <p>Background</p> <p>Boar taint is an unpleasant condition of pork, mainly due to the accumulation of androstenone and skatole in male pigs at onset of puberty. This condition is the cause of considerable economic losses in the pig industry and the most common practice to control it is to castrate male piglets. Because of the economic and animal welfare concerns there is interest in developing genetic markers that could be used in selection schemes to decrease the incidence of boar taint. The Porcine 60 K SNP Beadchip was used to genotype 891 pigs from a composite Duroc sire line, for which skatole levels in fat had been collected.</p> <p>Results</p> <p>The genome-wide association study revealed that 16 SNPs (single nucleotide polymorphisms) located on the proximal region of chromosome 6 were significantly associated with skatole levels. These SNPs are grouped in three separate clusters located in the initial 6 Mb region of chromosome 6. The differences observed between the homozygote genotypes for SNPs in the three clusters were substantial, including a difference of 102.8 ng/g skatole in melted fat between the homozygotes for the ALGA0107039 marker. Single SNPs explain up to 22% of the phenotypic variance. No obvious candidate genes could be pinpointed in the region, which may be due to the need of further annotation of the pig genome.</p> <p>Conclusions</p> <p>This study demonstrated new SNP markers significantly associated with skatole levels in the distal region of chromosome 6p. These markers defined three independent clusters in the region, which contain a low number of protein-coding genes. The considerable differences observed between the homozygous genotypes for several SNPs may be used in future selection schemes to reduce skatole levels in pigs</p

A Minimal Model of Metabolism Based Chemotaxis

Since the pioneering work by Julius Adler in the 1960's, bacterial chemotaxis has been predominantly studied as metabolism-independent. All available simulation models of bacterial chemotaxis endorse this assumption. Recent studies have shown, however, that many metabolism-dependent chemotactic patterns occur in bacteria. We hereby present the simplest artificial protocell model capable of performing metabolism-based chemotaxis. The model serves as a proof of concept to show how even the simplest metabolism can sustain chemotactic patterns of varying sophistication. It also reproduces a set of phenomena that have recently attracted attention on bacterial chemotaxis and provides insights about alternative mechanisms that could instantiate them. We conclude that relaxing the metabolism-independent assumption provides important theoretical advances, forces us to rethink some established pre-conceptions and may help us better understand unexplored and poorly understood aspects of bacterial chemotaxis

Novel insight into the genomic architecture of feed and nitrogen efficiency measured by residual energy intake and nitrogen excretion in growing pigs

Background Improvement of feed efficiency in pigs is of great economical and environmental interest and contributes to use limited resources efficiently to feed the world population. Genome scans for feed efficiency traits are of importance to reveal the underlying biological causes and increase the rate of genetic gain. The aim of this study was to determine the genomic architecture of feed efficiency measured by residual energy intake (REI), in association with production, feed conversion ratio (FCR) and nitrogen excretion traits through the identification of quantitative trait loci (QTL) at different stages of growth using a three generation full-sib design population which originated from a cross between Pietrain and a commercial dam line. Results Six novel QTL for REI were detected explaining 2.7-6.1% of the phenotypic variance in REI. At growth from 60–90 kg body weight (BW), a QTL with a significant dominance effect was identified for REI on SSC14, at a similar location to the QTL for feed intake and nitrogen excretion traits. At growth from 90–120 kg BW, three QTL for REI were detected on SSC2, SSC4 and SSC7 with significant additive, imprinting and additive effects, respectively. These QTL (except for the imprinted QTL) were positionally overlapping with QTL for FCR and nitrogen excretion traits. During final growth (120–140 kg BW), a further QTL for REI was identified on SSC8 with significant additive effect, which overlapped with QTL for nitrogen excretion. During entire analysed growth (60–140 kg BW), a novel additive QTL for REI on SSC4 was observed, with no overlapping with QTL for any other traits considered. Conclusions The occurrence of only one overlapping QTL of REI with feed intake suggests that only a small proportion of the variance in REI was explained by change in feed intake, whereas four overlapping QTL of REI with those of nitrogen excretion traits suggests that mostly underlying factors of feed utilisation such as metabolism and protein turnover were the reason for change in REI. Different QTL for REI were identified at different growth stages, indicating that different genes are responsible for efficiency in feed utilisation at different stages of growth

Structural basis for CRISPR RNA-guided DNA recognition by Cascade

The CRISPR (clustered regularly interspaced short palindromic repeats) immune system in prokaryotes uses small guide RNAs to neutralize invading viruses and plasmids. In Escherichia coli, immunity depends on a ribonucleoprotein complex called Cascade. Here we present the composition and low-resolution structure of Cascade and show how it recognizes double-stranded DNA (dsDNA) targets in a sequence-specific manner. Cascade is a 405-kDa complex comprising five functionally essential CRISPR-associated (Cas) proteins (CasA1B2C6D1E1) and a 61-nucleotide CRISPR RNA (crRNA) with 5′-hydroxyl and 2′,3′-cyclic phosphate termini. The crRNA guides Cascade to dsDNA target sequences by forming base pairs with the complementary DNA strand while displacing the noncomplementary strand to form an R-loop. Cascade recognizes target DNA without consuming ATP, which suggests that continuous invader DNA surveillance takes place without energy investment. The structure of Cascade shows an unusual seahorse shape that undergoes conformational changes when it binds target DNA.

The Evolution of Functionally Redundant Species; Evidence from Beetles

While species fulfill many different roles in ecosystems, it has been suggested that numerous species might actually share the same function in a near neutral way. So-far, however, it is unclear whether such functional redundancy really exists. We scrutinize this question using extensive data on the world’s 4168 species of diving beetles. We show that across the globe these animals have evolved towards a small number of regularly-spaced body sizes, and that locally co-existing species are either very similar in size or differ by at least 35%. Surprisingly, intermediate size differences (10–20%) are rare. As body-size strongly reflects functional aspects such as the food that these generalist predators can eat, these beetles thus form relatively distinct groups of functional look-a-likes. The striking global regularity of these patterns support the idea that a self-organizing process drives such species-rich groups to self-organize evolutionary into clusters where functional redundancy ensures resilience through an insurance effect

Providing perioperative care for patients with hip fractures

Providing perioperative care for patients with hip fractures can present major challenges for the anaesthesiologist. These patients often have multiple comorbidities, the deterioration of any one of which may have precipitated the fall. A careful balance has to be achieved between minimising the time before operation and spending time to optimise their medical status. This review will present insights into preoperative patient assessment and optimization in this group of patients from the anaesthesiologists’ perspective. In particular, it will highlight important medical issues of concern that may alter anaesthetic risks and management. With a greater understanding of what these issues are, potentially a more prompt and integrated approach to managing these patients may be made. Hopefully, this would result in minimising last minute cancellations due to medical reasons for these patients

The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial

Contains fulltext : 109739.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime. METHODS/DESIGN: Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged < 44 years, have a regular menstrual cycle and no major abnormalities at transvaginal sonography. Women with polycystic ovary syndrome, endocrine or metabolic abnormalities and women undergoing IVF with oocyte donation, will not be included. Ovarian reserve will be assessed by measuring the antral follicle count. Women with a predicted poor response or hyperresponse will be randomised for a standard versus an individualised FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of subfertile women outweigh the additional costs of an ORT. DISCUSSION: The results of this study will be integrated into a decision model that compares cost-effectiveness of the three dose-adjustment strategies to a standard dose strategy. The study outcomes will provide scientific foundation for national and international guidelines. TRIAL REGISTRATION: NTR2657

Topical use of MMC in the upper aerodigestive tract: a review on the side effects

Not much is known about the side effects of mitomycin C (MMC), an anti-fibrogenetic agent, in the upper aerodigestive tract. However, its use in ophthalmology is widely known and without quantitatively important side effects. A literature review was performed for side effects of MMC in the upper aerodigestive tract. Forty-six articles, describing the use of MMC to prevent scarring, were retracted from PubMed. Thirty-two are human studies. MMC is used in different concentrations (0.1–10 mg/ml) with different application times (2–5 min) and frequencies (up to 4 times). Five hundred and thirty-eight patients were included in those publications, of whom 19 developed side effects (3.53%). No side effects developed in studies, where post-application irrigation with saline was reported. The longest mean follow-up period is 75.5 months. Direct relations between the reported side effects and MMC seem absent in most studies. Serious complications seem to occur when MMC is used in high concentrations. Unfortunately, sometimes crucial information is lacking. One patient was described who supposedly developed laryngeal carcinoma after repeated treatment of hyperkeratosis and anterior commissure webbing. Animal studies show that excessive fibrin production can lead to acute airway obstruction. In conclusion, topical application of MMC on a wound with consecutive irrigation with saline can be performed safely to prevent scar formation in circular structures of the upper aerodigestive tract. Long-term yearly control of the application site seems advisable