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In response to the type 2 diabetes epidemic, measuring HbA1c with the first-antenatal blood screen was recently recommended in NZ. This would enable prompt treatment of women with unrecognised type 2 diabetes, who may otherwise go undetected until the gestational diabetes (GDM) screen. We compare inter-ethnic antenatal screening practices to examine whether the HbA1c test would be accessed by ethnicities most at risk of diabetes, and we determined the prevalence of unrecognised type 2 diabetes and prediabetes in our pregnant population. This is an observational study of pregnancies in Christchurch NZ during 2008-2010. Utilising electronic databases, we matched maternal characteristics to first-antenatal bloods, HbA1c, and GDM screens (glucose challenge tests and oral glucose tolerance tests). Overall uptake of the first-antenatal bloods versus GDM screening was 83.1% and 53.8% respectively in 11,580 pregnancies. GDM screening was lowest in Māori 39.3%, incidence proportion ratio (IPR) 0.77 (0.71, 0.84) compared with Europeans. By including HbA1c with the first-antenatal bloods, the number screened for diabetes increases by 28.5% in Europeans, 40.0% in Māori, 28.1% in Pacific People, and 26.7% in 'Others' (majority of Asian descent). The combined prevalence of unrecognised type 2 diabetes and prediabetes by NZ criteria, HbA1c ≥5.9% (41mmol/mol), was 2.1% in Europeans, Māori 4.7% IPR 2.59 (1.71, 3.93), Pacific People 9.5% IPR 4.76 (3.10, 7.30), and 'Others' 6.2% IPR 2.99 (2.19, 4.07). Applying these prevalence data to 2013 NZ national births data, routine antenatal HbA1c testing could have identified type 2 diabetes in 0.44% and prediabetes in 3.96% of women. Routine HbA1c measurement in early pregnancy is an ideal screening opportunity, particularly benefitting vulnerable groups, reducing ethnic disparities in antenatal diabetes screening. This approach is likely to have world-wide relevance and applicability. Further research is underway to establish whether, as for type 2 diabetes, prompt treatment of prediabetes improves pregnancy and neonatal outcomes.

During the repair of some rotator-cuff tears, the torn tendon cannot be freed up adequately to permit reattachment at its original anatomical site of insertion. An option is to advance the site of insertion medially and reattach the tendon to a trough in the sulcus or to the humeral head. The biomechanical effects of such medial advancement on the moment arm of the supraspinatus muscle during glenohumeral elevation were studied in ten fresh-frozen shoulders from cadavera. Medial advancement of the site of insertion of the supraspinatus tendon was simulated by the placement of suture anchors in the sulcus of the proximal part of the humerus at points three, ten, and seventeen millimeters medial to the junction of the supraspinatus tendon and the bone. These distances were chosen not because they represent clinical options but because the large range allowed biomechanical study of medial advancement. Nylon lines were attached to the suture anchors and were passed back through an eyehook at the midpoint of the supraspinatus muscle. The excursion of each line was measured as the humerus was elevated, and the moment arm was estimated from the joint angle and excursion data with use of the principle of virtual work. Three and ten millimeters of medial advancement of the tendon (attachment in the sulcus) had a minimum (non-significant) effect on the moment arm during elevation compared with the value determined for the intact condition. However, seventeen millimeters of medial advancement was found to reduce the moment arm significantly (p < 0.05). CLINICAL RELEVANCEOur study of cadavera indicates that a limited amount of medial advancement (as much as ten millimeters) is acceptable from a biomechanical point of view, although the clinical maximum is dictated by other clinical factors.

Expanded polyglutamine tracts are responsible for at least eight fatal neurodegenerative diseases. In mouse models, proteins with expanded polyglutamine cause transcriptional dysregulation before onset of symptoms, suggesting that this dysregulation may be an early event in polyglutamine pathogenesis. Transcriptional dysregulation and cellular toxicity may be due to interaction between expanded polyglutamine and the histone acetyltransferase CREB-binding protein. To determine whether polyglutamine-mediated transcriptional dysregulation occurs in yeast, we expressed polyglutamine tracts in Saccharomyces cerevisiae. Gene expression profiles were determined for strains expressing either a cytoplasmic or nuclear protein with 23 or 75 glutamines, and these profiles were compared to existing profiles of mutant yeast strains. Transcriptional induction of genes encoding chaperones and heat-shock factors was caused by expression of expanded polyglutamine in either the nucleus or cytoplasm. Transcriptional repression was most prominent in yeast expressing nuclear expanded polyglutamine and was similar to profiles of yeast strains deleted for components of the histone acetyltransferase complex Spt/Ada/Gcn5 acetyltransferase (SAGA). The promoter from one affected gene (PHO84) was repressed by expanded polyglutamine in a reporter gene assay, and this effect was mitigated by the histone deacetylase inhibitor, Trichostatin A. Consistent with an effect on SAGA, nuclear expanded polyglutamine enhanced the toxicity of a deletion in the SAGA component SPT3. Thus, an early component of polyglutamine toxicity, transcriptional dysregulation, is conserved in yeast and is pharmacologically antagonized by a histone deacetylase inhibitor. These results suggest a therapeutic approach for treatment of polyglutamine diseases and provide the potential for yeast-based screens for agents that reverse polyglutamine toxicity.

Although variability of anthropometric measures within a population is a well established phenomenon, most biomechanical models are based on average parameter values. For example, optimisation models for predicting muscle forces from net joint reaction moments typically use average muscle moment arms. However, understanding the distribution of musculoskeletal morbidity within a population requires information about the variation of tissue loads within the population. This study investigated the use of Monte Carlo simulation techniques to predict the statistical distribution of deltoid and rotator cuff muscle forces during static arm elevation. Muscle moment arms were modelled either as independent random variables or jointly distributed random variables. Moment arm data was collected on 22 cadaver specimens. The results demonstrated the use of Monte Carlo techniques to describe the statistical distribution of muscle forces. Although assuming statistically independent moment arms did affect the statistical distribution shape, that assumption did not affect the median predicted forces. The standard deviations of muscle forces predicted using Monte Carlo techniques were similar to the standard deviation of muscle force predictions using the whole sample of specimens. It is concluded that Monte Carlo simulation techniques are a useful tool to analyse the interindividual variability of rotator cuff muscle forces.

Polyglutamine diseases comprise a class of familial neurodegenerative disorders caused by expression of proteins containing expanded polyglutamine tracts. Great progress has been made in elucidating the molecular mechanisms contributing to polyglutamine pathology, and in identifying potential drug targets. Although much remains to be learned, these advances provide an opportunity for rational approaches to target-based drug discovery.

Astrophysical jet power A small fraction of active galaxies are extreme phenomena, powered by the release of gravitational energy near the supermassive black hole at the galaxy's centre. Just what goes on in the emitting zone, where inflowing gases interact with the outflowing jets, is not clear. One such extreme object is the blazar 3C 279. Multi-band observations of 3C 279 using the Fermi space telescope have revealed a spectacular γ-ray flare coincident with a dramatic change of optical polarization angle. This points to co-spatiality of the optical and γ-ray emission regions and indicates a highly ordered jet magnetic field. Future observation of cosmic accelerators of this type should throw light on how the immense power required to accelerate matter to close to the speed of light is generated. It is widely accepted that strong and variable radiation detected over all accessible energy bands in a number of active galaxies arises from a relativistic, Doppler-boosted jet pointing close to our line of sight. However, the size of the emitting zone and the location of this region relative to the central supermassive black hole are poorly understood. Here, the coincidence of a γ-ray flare with a dramatic change of optical polarization angle is reported, providing evidence for co-spatiality of optical and γ-ray emission regions and indicating a highly ordered jet magnetic field. It is widely accepted that strong and variable radiation detected over all accessible energy bands in a number of active galaxies arises from a relativistic, Doppler-boosted jet pointing close to our line of sight 1 . The size of the emitting zone and the location of this region relative to the central supermassive black hole are, however, poorly known, with estimates ranging from light-hours to a light-year or more. Here we report the coincidence of a gamma (γ)-ray flare with a dramatic change of optical polarization angle. This provides evidence for co-spatiality of optical and γ-ray emission regions and indicates a highly ordered jet magnetic field. The results also require a non-axisymmetric structure of the emission zone, implying a curved trajectory for the emitting material within the jet, with the dissipation region located at a considerable distance from the black hole, at about 10 5 gravitational radii.

Most biologists operate like reputable journalists, faithfully reporting on what's happening in the world but wary of straying into the realm of invention. Much of what is reported in biology, however, is old news: the deeds and associations of macromolecules that have evolved over millions of years. But some biologists are more akin to playwrights. Rather than uncovering and chronicling the habits of the characters nature provides us, they prefer instead to invent characters and direct their actions on the stage. However, there really are no new characters under the sun, and the skill of a dramatist lies in the facility with which the old stock is refashioned into novel and unexpected situations. And so is the case with the work reported in this issue by Schneider et al., which describes the use of the yeast two-hybrid system to select artificial PDZ domains that bind one of four peptide ligands with high specificity and affinity.

Millisecond pulsars, old neutron stars spun up by accreting matter from a companion star, can reach high rotation rates of hundreds of revolutions per second. Until now, all such \"recycled\" rotation-powered pulsars have been detected by their spin-modulated radio emission. In a computing-intensive blind search of gamma-ray data from the Fermi Large Area Telescope (with partial constraints from optical data), we detected a 2.5-millisecond pulsar, PSR J1311—3430. This unambiguously explains a formerly unidentified gamma-ray source that had been a decade-long enigma, confirming previous conjectures. The pulsar is in a circular orbit with an orbital period of only 93 minutes, the shortest of any spin-powered pulsar binary ever found.

What makes a parasite tick A powerful approach for understanding protein function is to identify which proteins bind to each other, as protein complexes are at the heart of most biological processes. Protein–protein interactions have now been mapped for one quarter of the malaria parasite's proteins. This large data set sheds new light on how parasites infect red blood cells and will be a vital tool for the development of new antimalarial drugs and vaccines. The primary data are freely available on the PlasmoDB database. Suthram et al . have used this new resource and find that the Plasmodium network has significantly less cross-species similarity than other eukaryotes. Its novel life style is reflected in a novel protein network, which therefore has a good chance of providing drug targets unique to the malaria parasite. Plasmodium falciparum causes the most severe form of malaria and kills up to 2.7 million people annually 1 . Despite the global importance of P. falciparum , the vast majority of its proteins have not been characterized experimentally. Here we identify P. falciparum protein–protein interactions using a high-throughput version of the yeast two-hybrid assay that circumvents the difficulties in expressing P. falciparum proteins in Saccharomyces cerevisiae . From more than 32,000 yeast two-hybrid screens with P. falciparum protein fragments, we identified 2,846 unique interactions, most of which include at least one previously uncharacterized protein. Informatic analyses of network connectivity, coexpression of the genes encoding interacting fragments, and enrichment of specific protein domains or Gene Ontology annotations 2 were used to identify groups of interacting proteins, including one implicated in chromatin modification, transcription, messenger RNA stability and ubiquitination, and another implicated in the invasion of host cells. These data constitute the first extensive description of the protein interaction network for this important human pathogen.