Marsupials and monotremes sort genome treasures from junk

A recent landmark paper demonstrates the unique contribution of marsupials and monotremes to comparative genome analysis, filling an evolutionary gap between the eutherian mammals (including humans) and more distant vertebrate species

Marsupials and monotremes sort genome treasures from junk

A recent landmark paper demonstrates the unique contribution of marsupials and monotremes to comparative genome analysis, filling an evolutionary gap between the eutherian mammals (including humans) and more distant vertebrate species

Regulation of Human Cytidine Triphosphate Synthetase 1 by Glycogen Synthase Kinase 3

Cytidine triphosphate synthetase (CTPS) catalyzes the rate-limiting step in the de novo synthesis of CTP, and both the yeast and human enzymes have been reported to be regulated by protein kinase A or protein kinase C phosphorylation. Here, we provide evidence that stimulation or inhibition of protein kinase A and protein kinase C does not alter the phosphorylation of endogenous human CTPS1 in human embryonic kidney 293 cells under the conditions tested. Unexpectedly, we found that low serum conditions increased phosphorylation of endogenous CTPS1 and this phosphorylation was inhibited by the glycogen synthase kinase 3 (GSK3) inhibitor indirubin-3'-monoxime and GSK3beta short interfering RNAs, demonstrating the involvement of GSK3 in phosphorylation of endogenous human CTPS1. Separating tryptic peptides from [(32)P]orthophosphate-labeled cells and analyzing the phosphopeptides by mass spectrometry identified Ser-574 and Ser-575 as phosphorylated residues. Mutation of Ser-571 demonstrated that Ser-571 was the major site phosphorylated by GSK3 in intact human embryonic kidney 293 cells by GSK3 in vitro. Furthermore, mutation of Ser-575 prevented the phosphorylation of Ser-571, suggesting that phosphorylation of Ser-575 was necessary for priming the GSK3 phosphorylation of Ser-571. Low serum was found to decrease CTPS1 activity, and incubation with the GSK3 inhibitor indirubin-3'-monoxime protected against this decrease in activity. Incubation with an alkaline phosphatase increased CTPS1 activity in a time-dependent manner, demonstrating that phosphorylation inhibits CTPS1 activity. This is the first study to investigate the phosphorylation and regulation of human CTPS1 in human cells and suggests that GSK3 is a novel regulator of CTPS activity

The reliability of the Tracheoesophageal Groove and the Ligament of Berry as landmarks for identifying the Recurrent Laryngeal Nerve : a cadaveric study and meta-analysis

Purpose. The aim of this meta-analysis was to provide a comprehensive evidence-based assessment, supplemented by cadaveric dissections, of the value of using the Ligament of Berry and Tracheoesophageal Groove as anatomical landmarks for identifying the Recurrent Laryngeal Nerve. Methods. Seven major databases were searched to identify studies for inclusion. Eligibility was judged by two reviewers. Suitable studies were identified and extracted. MetaXL was used for analysis. All pooled prevalence rates were calculated using a random effects model. Heterogeneity among included studies was assessed using the Chi2 test and the I2 statistic. Results. Sixteen studies (n=2,470 nerves), including original cadaveric data, were analyzed for the BL/RLN relationship. The RLN was most often located superficial to the BL with a pooled prevalence estimate of 78.2% of nerves, followed by deep to the BL in 14.8%. Twenty-three studies (n=5,970 nerves) examined the RLN/TEG relationship. The RLN was located inside the TEG in 63.7% (95% CI: 55.3–77.7) of sides. Conclusions. Both the BL and TEG are landmarks that can help surgeons provide patients with complication-free procedures. Our analysis showed that the BL is a more consistent anatomical landmark than the TEG, but it is necessary to use both to prevent iatrogenic RLN injuries during thyroidectomies

Extralaryngeal branching of the recurrent laryngeal nerve : a meta-analysis of 28,387 nerves

INTRODUCTION: The recurrent laryngeal nerves (RLN) are branches of the vagus nerve that go on to innervate most of the intrinsic muscles of the larynx. Historically, the RLN has been considered to branch after it enters the larynx, but numerous studies have demonstrated that it often branches before. The wide variability of this extralaryngeal branching (ELB) has significant implications for the risk of iatrogenic injury. We aimed to assess the anatomical characteristics of ELB comprehensively. METHODS: Articles on the ELB of the RLN were identified by a comprehensive database search. Relevant data were extracted and pooled into a meta-analysis of the prevalence of branching, branching pattern, distance of ELB point from the larynx, and presence of positive motor signals in anterior and posterior ELB branches. RESULTS: A total of 69 articles (n = 28,387 nerves) from both intraoperative and cadaveric modalities were included in the meta-analysis. The overall pooled prevalence of ELB was 60.0 % (95 % CI 52.0–67.7). Cadaveric and intraoperative subgroups differed with prevalence rates of 73.3 % (95 % CI 61.0–84.0) and 39.2 % (95 % CI 29.0–49.9), respectively. Cadavers most often presented with a ELB pattern of bifurcation, with a prevalence of 61.1 %, followed by no branching at 23.4 %. Branching of the RLN occurred most often at a distance of 1–2 cm (74.8 % of cases) prior to entering the larynx. A positive motor signal was most often noted in anterior RLN branches (99.9 %) but only in 1.5 % of posterior branches. CONCLUSIONS: The anatomy of the RLN is highly variable, and ELB is likely to have been underreported in intraoperative studies. Because of its high likelihood, the possibility of ELB needs to be assessed in patients to prevent iatrogenic injury and long-term postoperative complications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00423-016-1455-7) contains supplementary material, which is available to authorized users

The Non-Recurrent Laryngeal Nerve : a meta-analysis and clinical considerations

Background The Non-Recurrent Laryngeal Nerve (NRLN) is a rare embryologically-derived variant of the Recurrent Laryngeal Nerve (RLN). The presence of an NRLN significantly increases the risk of iatrogenic injury and operative complications. Our aim was to provide a comprehensive meta-analysis of the overall prevalence of the NRLN, its origin, and its association with an aberrant subclavian artery. Methods Through March 2016, a database search was performed of PubMed, CNKI, ScienceDirect, EMBASE, BIOSIS, SciELO, and Web of Science. The references in the included articles were also extensively searched. At least two reviewers judged eligibility and assessed and extracted articles. MetaXL was used for analysis, with all pooled prevalence rates calculated using a random effects model. Heterogeneity among the included studies was assessed using the Chi2 test and the I2 statistic. Results Fifty-three studies (33,571 right RLNs) reported data on the prevalence of a right NRLN. The pooled prevalence estimate was 0.7% (95% CI [0.6–0.9]). The NRLN was found to originate from the vagus nerve at or above the laryngotracheal junction in 58.3% and below it in 41.7%. A right NRLN was associated with an aberrant subclavian artery in 86.7% of cases. Conclusion The NRLN is a rare yet very clinically relevant structure for surgeons and is associated with increased risk of iatrogenic injury, most often leading to temporary or permanent vocal cord paralysis. A thorough understanding of the prevalence, origin, and associated pathologies is vital for preventing injuries and complications

The initial mass function of early-type galaxies

We determine an absolute calibration of the initial mass function (IMF) of early-type galaxies, by studying a sample of 56 gravitational lenses identified by the SLACS Survey. Under the assumption of standard Navarro, Frenk & White dark matter halos, a combination of lensing, dynamical, and stellar population synthesis models is used to disentangle the stellar and dark matter contribution for each lens. We define an "IMF mismatch" parameter \alpha=M*(L+D)/M*(SPS) as the ratio of stellar mass inferred by a joint lensing and dynamical models (M*(L+D)) to the current stellar mass inferred from stellar populations synthesis models (M*(SPS)). We find that a Salpeter IMF provides stellar masses in agreement with those inferred by lensing and dynamical models (=0.00+-0.03+-0.02), while a Chabrier IMF underestimates them (=0.25+-0.03+-0.02). A tentative trend is found, in the sense that \alpha appears to increase with galaxy velocity dispersion. Taken at face value, this result would imply a non universal IMF, perhaps dependent on metallicity, age, or abundance ratios of the stellar populations. Alternatively, the observed trend may imply non-universal dark matter halos with inner density slope increasing with velocity dispersion. While the degeneracy between the two interpretations cannot be broken without additional information, the data imply that massive early-type galaxies cannot have both a universal IMF and universal dark matter halos.Comment: 10 pages 4 figures. Resubmitted to ApJ taking into account referee's comment