Digit ratio (2D:4D) and rowing ergometer performance in males and females.

Fetal and adult testosterone may be vital in the establishment and maintenance of sex-dependent abilities associated with male physical competitiveness. It has been shown that digit ratio (2D:4D) is negatively associated with prenatal testosterone, and it is also negatively associated with ability in sports such as football, skiing, middle distance running, and endurance running, which are dependent upon an efficient cardiovascular system. The relationship between digit ratio and sports requiring high power (physical strength) output in addition to well-developed cardiovascular systems has not been defined. This study investigated this association in male and female young adult rowers. Participants (77 male and 70 female) were student rowers encompassing a range of abilities from the University of Cambridge. Bilateral digit measurements were taken blind from each subject using Mitutoyo vernier calipers. Rowing performance over 2,000 m was assessed using the Concept 2 rowing ergometer. Significant negative correlations were observed between 2,000 m ergometer performance and male digit ratios, which persisted following adjustment for rowing experience and height. However, no such significant association was found in females despite a comparable sample size. Our data indicate that digit ratio is a predictor of ability in rowing, a sport which requires both cardiovascular efficiency and high power output, in males but not females. This in turn suggests that fetal testosterone exposure has long-term effects on traits associated with physical power in males but not females, suggesting a sex-difference in the capacity to respond to such exposures.

Fluctuating asymmetry as a predictor for rowing ergometer performance.

Fluctuating asymmetry (FA) can be defined as an organism's deviation from perfect bilateral symmetry. FA has been of interest to evolutionary biologists as it may be indicative of the ability of an individual to express its genotype in a stable manner. Asymmetry has been shown to correlate with success in both intra- and inter-sexual selection in various species, including humans. A growing body of knowledge is emerging concerning the relationship between asymmetry and sporting ability. This study seeks to expand upon understanding of developmental stability and athletics by investigating the association between asymmetry and performance in rowers. Both male and female competitors from a range of abilities were tested (76 males and 70 females), with asymmetry being determined through bilateral digit measurements and performance through personal best time over 2000 m on the Concept 2 indoor rowing ergometer. Significant negative correlations were observed between asymmetry and 2000 m ergometer performance in both males and females. The relationship remained significant after adjustment for rowing experience and height. These results suggest that asymmetry may serve as a predictor of potential ability in the sport of rowing. The cause for the association between asymmetry and sporting performance has yet to be identified.

Multiple interactions between SRm160 and SR family proteins in enhancer-dependent splicing and development of C. elegans.

BACKGROUND: SR family and SR-related proteins assemble on exonic splicing enhancer (ESE) sequences to promote both constitutive and regulated splicing. The SRm160 splicing coactivator, an SR-related nuclear matrix protein of 160 kDa, is important for the splicing of specific constitutive and ESE-dependent pre-mRNAs. RESULTS: In the present study, we show that SRm160 is required to promote pre-mRNA splicing mediated by a large population of functional ESE sequences within a randomized 18 nucleotide sequence. This suggests that it functions as a general coactivator by interacting with different SR family/SR-related proteins bound to different ESE sequences. Consistent with this, several SR family and SR-related proteins coimmunoprecipitated specifically with SRm160 in the presence of low salt. We used RNA interference (RNAi) in Caenorhabditis elegans to determine whether interactions between CeSRm160 and different CeSR family proteins are important in a whole-organism context. Previously we showed that RNAi of CeSRm160 and individual CeSR family genes other than CeSF2/ASF results in no obvious phenotype, which is indicative of gene redundancy. In the present study, we demonstrate that RNAi of CeSRm160 in combination with any CeSR family gene results in the production of unfertilized oocytes by the injected mother. CONCLUSIONS: The observation that simultaneous suppression of CeSRm160 and individual CeSR family proteins results in a distinct phenotype is indicative of critical functional interactions between these factors. Our results provide biochemical and genetic evidence indicating that interactions between SRm160 and multiple SR family proteins are important for both optimal splicing activity and for proper development.

Compound heterozygous variants in NBAS as a cause of atypical osteogenesis imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI), the commonest inherited bone fragility disorder, affects 1 in 15,000 live births resulting in frequent fractures and reduced mobility, with significant impact on quality of life. Early diagnosis is important, as therapeutic advances can lead to improved clinical outcome and patient benefit. REPORT: Whole exome sequencing in patients with OI identified, in two patients with a multi-system phenotype, compound heterozygous variants in NBAS (neuroblastoma amplified sequence). Patient 1: NBAS c.5741G>A p.(Arg1914His); c.3010C>T p.(Arg1004*) in a 10-year old boy with significant short stature, bone fragility requiring treatment with bisphosphonates, developmental delay and immunodeficiency. Patient 2: NBAS c.5741G>A p.(Arg1914His); c.2032C>T p.(Gln678*) in a 5-year old boy with similar presenting features, bone fragility, mild developmental delay, abnormal liver function tests and immunodeficiency. DISCUSSION: Homozygous missense NBAS variants cause SOPH syndrome (short stature; optic atrophy; Pelger-Huet anomaly), the same missense variant was found in our patients on one allele and a nonsense variant in the other allele. Recent literature suggests a multi-system phenotype. In this study, patient fibroblasts have shown reduced collagen expression, compared to control cells and RNAseq studies, in bone cells show that NBAS is expressed in osteoblasts and osteocytes of rodents and primates. These findings provide proof-of-concept that NBAS mutations have mechanistic effects in bone, and that NBAS variants are a novel cause of bone fragility, which is distinguishable from 'Classical' OI. CONCLUSIONS: Here we report on variants in NBAS, as a cause of bone fragility in humans, and expand the phenotypic spectrum associated with NBAS. We explore the mechanism underlying NBAS and the striking skeletal phenotype in our patients.

A method for measuring drug-induced changes in limb muscle tone in the rat.

A method for measuring the time-course and magnitude of changes in rat hind leg muscle tone in vivo is described in detail. The rat is held in a restraining box and the apparatus pushes each hindpaw from behind a distance of 1 cm and measures the force required to briefly hold each leg in the displaced position. The push-relax cycle is repeated every 45 s. Identical measurements were obtained from the 2 hind legs. Experimental results are presented to demonstrate the potential of the technique for investigating the effects of drugs on muscle tone. Morphine, which is known to cause rigidity, increased the force required to displace the hind legs. Muscle tone was reduced in rats that were lightly anaesthetized.

Effects of intrapallidal drugs on hyperactivity induced by nucleus accumbens dopamine receptor stimulation.

The effect of manipulating globus pallidus (GP) transmitters on the locomotor hyperactivity induced by administration of the dopamine agonist ADTN in the nucleus accumbens was investigated in rats with permanent intracerebral cannulae. Hyperactivity was antagonized by the GABA agonists muscimol and baclofen and the GABA antagonist bicuculline. Atropine, ADTN and ethylketazocine in GP had no effects on the response. Both morphine and the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine prevented the hyperactivity. The findings emphasize the role of GP GABA in the NA-induced hyperactivity and provide information about the functions of some other GP transmitters.

Functional characterization of SR and SR-related genes in Caenorhabditis elegans.

The SR proteins constitute a family of nuclear phosphoproteins, which are required for constitutive splicing and also influence alternative splicing regulation. Initially, it was suggested that SR proteins were functionally redundant in constitutive splicing. However, differences have been observed in alternative splicing regulation, suggesting unique functions for individual SR proteins. Homology searches of the Caenorhabditis elegans genome identified seven genes encoding putative orthologues of the human factors SF2/ASF, SRp20, SC35, SRp40, SRp75 and p54, and also several SR-related genes. To address the issue of functional redundancy, we used dsRNA interference (RNAi) to inhibit specific SR protein function during C.elegans development. RNAi with CeSF2/ASF caused late embryonic lethality, suggesting that this gene has an essential function during C.elegans development. RNAi with other SR genes resulted in no obvious phenotype, which is indicative of gene redundancy. Simultaneous interference of two or more SR proteins in certain combinations caused lethality or other developmental defects. RNAi with CeSRPK, an SR protein kinase, resulted in early embryonic lethality, suggesting an essential role for SR protein phosphorylation during development.

An in vivo method for testing putative GABA-like compounds.

A technique is described that enables compounds with GABA-ergic properties to be rapidly identified in vivo. Electrical stimulation of the neostriatum in the conscious rat evoked a contralateral head-turn. Evidence is presented that this easily timed motor response involves, at least in part, GABA-ergic mechanisms in the globus pallidus. GABA drugs were injected through a cannula into the ipsilateral globus pallidus and their effects on head-turning observed. Known GABA agonists including muscimol slowed the head-turn, whereas the GABA antagonist picrotoxin facilitated it. A number of drugs such as baclofen, diazepam, and pentobarbitone which have been attributed with GABA-like properties behaved like GABA agonists in the head-turn model following either intrapallidal or intraperitoneal injection. Other drugs, e.g. tranquillizers, with no known GABA-like properties, did not effect the head-turn time.