Incidence and risk factors for placenta accreta/increta/percreta in the UK: a national case-control study.

Placenta accreta/increta/percreta is associated with major pregnancy complications and is thought to be becoming more common. The aims of this study were to estimate the incidence of placenta accreta/increta/percreta in the UK and to investigate and quantify the associated risk factors

NF-κB Activity Initiates Human ESC-Derived Neural Progenitor Cell Differentiation by Inducing a Metabolic Maturation Program.

Human neural development begins at embryonic day 19 and marks the beginning of organogenesis. Neural stem cells in the neural tube undergo profound functional, morphological, and metabolic changes during neural specification, coordinated by a combination of exogenous and endogenous cues. The temporal cell signaling activities that mediate this process, during development and in the postnatal brain, are incompletely understood. We have applied gene expression studies and transcription factor-activated reporter lentiviruses during in vitro neural specification of human pluripotent stem cells. We show that nuclear factor κB orchestrates a multi-faceted metabolic program necessary for the maturation of neural progenitor cells during neurogenesis

Cryo-EM structure of the Rous sarcoma virus octameric cleaved synaptic complex intasome

Despite conserved catalytic integration mechanisms, retroviral intasomes composed of integrase (IN) and viral DNA possess diverse structures with variable numbers of IN subunits. To investigate intasome assembly mechanisms, we employed the Rous sarcoma virus (RSV) IN dimer that assembles a precursor tetrameric structure in transit to the mature octameric intasome. We determined the structure of RSV octameric intasome stabilized by a HIV-1 IN strand transfer inhibitor using single particle cryo-electron microscopy. The structure revealed significant flexibility of the two non-catalytic distal IN dimers along with previously unrecognized movement of the conserved intasome core, suggesting ordered conformational transitions between intermediates that may be important to capture the target DNA. Single amino acid substitutions within the IN C-terminal domain affected intasome assembly and function in vitro and infectivity of pseudotyped RSV virions. Unexpectedly, 17 C-terminal amino acids of IN were dispensable for virus infection despite regulating the transition of the tetrameric intasome to the octameric form in vitro. We speculate that this region may regulate the binding of highly flexible distal IN dimers to the intasome core to form the octameric complex. Our studies reveal key steps in the assembly of RSV intasomes

Nuclear Structure Relevant to Neutrinoless Double Beta Decay: 76Ge and 76Se

The possibility of observing neutrinoless double beta decay offers the opportunity of determining the neutrino mass IF the nuclear matrix element were known. Theoretical calculations are uncertain and measurements of the occupations of valence orbits by nucleons active in the decay can be important. The occupation of valence neutron orbits in the ground states of 76Ge and 76Se were determined by precisely measuring cross sections for both neutron-adding and removing transfer reactions. Our results indicate that the Fermi surface is much more diffuse than in theoretical (QRPA) calculations. We find that the populations of at least three orbits change significantly between these two ground states while in the calculations the changes are confined primarily to one orbit.Comment: 4 pages, 3 figure

The female perspective of personality in a wild songbird: repeatable aggressiveness relates to exploration behaviour

ABSTRACT: Males often express traits that improve competitive ability, such as aggressiveness. Females also express such traits but our understanding about why is limited. Intraspecific aggression between females might be used to gain access to reproductive resources but simultaneously incurs costs in terms of energy and time available for reproductive activities, resulting in a trade-off. Although consistent individual differences in female behaviour (i.e. personality) like aggressiveness are likely to influence these reproductive trade-offs, little is known about the consistency of aggressiveness in females. To quantify aggression we presented a female decoy to free-living female great tits (Parus major) during the egg-laying period, and assessed whether they were consistent in their response towards this decoy. Moreover, we assessed whether female aggression related to consistent individual differences in exploration behaviour in a novel environment. We found that females consistently differed in aggressiveness, although first-year females were on average more aggressive than older females. Moreover, conform life history theory predictions, ‘fast’ exploring females were more aggressive towards the decoy than ‘slow’ exploring females. Given that personality traits are often heritable, and correlations between behaviours can constrain short term adaptive evolution, our findings highlight the importance of studying female aggression within a multivariate behavioural framework

It Takes Two to Tango: Defining an Essential Second Active Site in Pyridoxal 5′-Phosphate Synthase

The prevalent de novo biosynthetic pathway of vitamin B6 involves only two enzymes (Pdx1 and Pdx2) that form an ornate multisubunit complex functioning as a glutamine amidotransferase. The synthase subunit, Pdx1, utilizes ribose 5-phosphate and glyceraldehyde 3-phosphate, as well as ammonia derived from the glutaminase activity of Pdx2 to directly form the cofactor vitamer, pyridoxal 5′-phosphate. Given the fact that a single enzyme performs the majority of the chemistry behind this reaction, a complicated mechanism is anticipated. Recently, the individual steps along the reaction co-ordinate are beginning to be unraveled. In particular, the binding of the pentose substrate and the first steps of the reaction have been elucidated but it is not known if the latter part of the chemistry, involving the triose sugar, takes place in the same or a disparate site. Here, we demonstrate through the use of enzyme assays, enzyme kinetics, and mutagenesis studies that indeed a second site is involved in binding the triose sugar and moreover, is the location of the final vitamin product, pyridoxal 5′-phosphate. Furthermore, we show that product release is triggered by the presence of a PLP-dependent enzyme. Finally, we provide evidence that a single arginine residue of the C terminus of Pdx1 is responsible for coordinating co-operativity in this elaborate protein machinery

FRA2A is a CGG repeat expansion associated with silencing of AFF3

Folate-sensitive fragile sites (FSFS) are a rare cytogenetically visible subset of dynamic mutations. Of the eight molecularly characterized FSFS, four are associated with intellectual disability (ID). Cytogenetic expression results from CGG tri-nucleotide-repeat expansion mutation associated with local CpG hypermethylation and transcriptional silencing. The best studied is the FRAXA site in the FMR1 gene, where large expansions cause fragile X syndrome, the most common inherited ID syndrome. Here we studied three families with FRA2A expression at 2q11 associated with a wide spectrum of neurodevelopmental phenotypes. We identified a polymorphic CGG repeat in a conserved, brain-active alternative promoter of the AFF3 gene, an autosomal homolog of the X-linked AFF2/FMR2 gene: Expansion of the AFF2 CGG repeat causes FRAXE ID. We found that FRA2A-expressing individuals have mosaic expansions of the AFF3 CGG repeat in the range of several hundred repeat units. Moreover, bisulfite sequencing and pyrosequencing both suggest AFF3 promoter hypermethylation. cSNP-analysis demonstrates monoallelic expression of the AFF3 gene in FRA2A carriers thus predicting that FRA2A expression results in functional haploinsufficiency for AFF3 at least in a subset of tissues. By whole-mount in situ hybridization the mouse AFF3 ortholog shows strong regional expression in the developing brain, somites and limb buds in 9.5-12.5dpc mouse embryos. Our data suggest that there may be an association between FRA2A and a delay in the acquisition of motor and language skills in the families studied here. However, additional cases are required to firmly establish a causal relationship

Guillain-Barré syndrome: a century of progress

In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts — novel findings that identified the disease we now know as Guillain–Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise. Subsequent work has, however, shown that primary axonal injury can be the underlying disease. The association of Campylobacter jejuni strains has led to confirmation that anti-ganglioside antibodies are pathogenic and that axonal GBS involves an antibody and complement-mediated disruption of nodes of Ranvier, neuromuscular junctions and other neuronal and glial membranes. Now, ongoing clinical trials of the complement inhibitor eculizumab are the first targeted immunotherapy in GBS

Species identification by experts and non-experts: comparing images from field guides

Accurate species identification is fundamental when recording ecological data. However, the ability to correctly identify organisms visually is rarely questioned. We investigated how experts and non-experts compared in the identification of bumblebees, a group of insects of considerable conservation concern. Experts and non-experts were asked whether two concurrent bumblebee images depicted the same or two different species. Overall accuracy was below 60% and comparable for experts and non-experts. However, experts were more consistent in their answers when the same images were repeated, and more cautious in committing to a definitive answer. Our findings demonstrate the difficulty of correctly identifying bumblebees using images from field guides. Such error rates need to be accounted for when interpreting species data, whether or not they have been collected by experts. We suggest that investigation of how experts and non-experts make observations should be incorporated into study design, and could be used to improve training in species identification

Association between insulin resistance and c-reactive protein among Peruvian adults

<p>Abstract</p> <p>Objective</p> <p>Insulin resistance (IR), a reduced physiological response of peripheral tissues to the action of insulin, is one of the major causes of type 2 diabetes. We sought to evaluate the relationship between serum C-reactive protein (CRP), a marker of systemic inflammation, and prevalence of IR among Peruvian adults.</p> <p>Methods</p> <p>This population based study of 1,525 individuals (569 men and 956 women; mean age 39 years old) was conducted among residents in Lima and Callao, Peru. Fasting plasma glucose, insulin, and CRP concentrations were measured using standard approaches. Insulin resistance was assessed using the homeostasis model (HOMA-IR). Categories of CRP were defined by the following tertiles: <0.81 mg/l, 0.81-2.53 mg/l, and >2.53 mg/l. Logistic regression procedures were employed to estimate odds ratios (OR) and 95% confidence intervals (CI).</p> <p>Results</p> <p>Elevated CRP were significantly associated with increased mean fasting insulin and mean HOMA-IR concentrations (p < 0.001). Women with CRP concentration >2.53 mg/l (upper tertile) had a 2.18-fold increased risk of IR (OR = 2.18 95% CI 1.51-3.16) as compared with those in the lowest tertile (<0.81 mg/l). Among men, those in the upper tertile had a 2.54-fold increased risk of IR (OR = 2.54 95% CI 1.54-4.20) as compared with those in the lowest tertile.</p> <p>Conclusion</p> <p>Our observations among Peruvians suggest that chronic systemic inflammation, as evidenced by elevated CRP, may be of etiologic importance in insulin resistance and diabetes.</p