Most bacteriophages possess long tails, which serve as the conduit for genome delivery. We report the solution structure of the N-terminal domain of gpV, the protein comprising the major portion of the noncontractile phage tail tube. This structure is very similar to a previously solved tail tube protein from a contractile-tailed phage, providing the first direct evidence of an evolutionary connection between these 2 distinct types of phage tails. A remarkable structural similarity is also seen to Hcp1, a component of the bacterial type VI secretion system. The hexameric structure of Hcp1 and its ability to form long tubes are strikingly reminiscent of gpV when it is polymerized into a tail tube. These data coupled with other similarities between phage and type VI secretion proteins support an evolutionary relationship between these systems. Using Hcp1 as a model, we propose a polymerization mechanism for gpV involving several disorder-toorder transitions.NMR structure ͉ disordered regions ͉ macromolecular assembly

BACKGROUNDCauses of early infant growth restriction remain incompletely understood. Where vitamin D deficiency is common, vitamin D supplementation during pregnancy and lactation may improve fetal-infant growth and other birth outcomes.METHODSWe conducted a randomized, double-blind, placebo-controlled trial of maternal vitamin D supplementation from 17-24 weeks gestation until birth or 6 months postpartum. Participants were randomly allocated to five vitamin D and/or placebo supplementation groups: (A) 0 IU/week, (B) 4200 IU/week, (C) 16800 IU/week, or (D) 28000 IU/week in pregnancy, all with 0 IU/week postpartum; or, (E) 28000 IU/week in prenatal and postpartum periods. The primary outcome was length-for-age z-score at one year of age according to World Health Organization child growth standards.RESULTSAmong 1164 infants assessed at one year of age (90% of 1300 pregnancies), there were no differences across groups in length-for-age z-scores (mean ±standard deviation): A: -0.93 ±1.05, B: -1.11 ±1.12, C: -0.97 ±0.97, D: -1.06 ±1.07, E: -0.94 ±1.00 (p=0.23). Groups were similar with respect to other anthropometric measures, birth outcomes, and morbidity. Vitamin D had dose- dependent effects on maternal and infant serum 25-hydroxyvitamin D and calcium, maternal urinary calcium excretion, and maternal parathyroid hormone concentrations. No clinical adverse events were attributed to the vitamin D intervention. CONCLUSIONSIn a population with widespread prenatal vitamin D deficiency and fetal/infant growth restriction, maternal vitamin D supplementation from mid-pregnancy until birth or 6 months postpartum does not influence fetal or infant growth, and has no beneficial or harmful effects on numerous other birth and infant outcomes.

In this chapter, we describe the structure, assembly, function, and evolution of the long, noncontractile tail of the siphophages, which comprise ∼60% of the phages on earth. We place -particular emphasis on features that are conserved among all siphophages, and trace evolutionary connections between these phages and myophages, which possess long contractile tails. The large number of high-resolution structures of tail proteins solved recently coupled to studies of tail-related complexes by electron microscopy have provided many new insights in this area. In addition, the availability of thousands of phage and prophage genome sequences has allowed the delineation of several large families of tail proteins that were previously unrecognized. We also summarize current knowledge pertaining to the mechanisms by which siphophage tails recognize the bacterial cell surface and mediate DNA injection through the cell envelope. We show that phages infecting Gram-positive and Gram-negative bacteria possess distinct families of proteins at their tail tips that are involved in this process. Finally, we speculate on the evolutionary advantages provided by long phage tails.

BackgroundFollowing independence from the Soviet Union in 1991, Estonia introduced a national insurance system, consolidated the number of health care providers, and introduced family medicine centred primary health care (PHC) to strengthen the health system.MethodsUsing routinely collected health billing records for 2005–2012, we examine health system utilisation for seven ambulatory care sensitive conditions (ACSCs) (asthma, chronic obstructive pulmonary disease [COPD], depression, Type 2 diabetes, heart failure, hypertension, and ischemic heart disease [IHD]), and by patient characteristics (gender, age, and number of co–morbidities). The data set contained 552 822 individuals. We use patient level data to test the significance of trends, and employ multivariate regression analysis to evaluate the probability of inpatient admission while controlling for patient characteristics, health system supply–side variables, and PHC use.FindingsOver the study period, utilisation of PHC increased, whilst inpatient admissions fell. Service mix in PHC changed with increases in phone, email, nurse, and follow–up (vs initial) consultations. Healthcare utilisation for diabetes, depression, IHD and hypertension shifted to PHC, whilst for COPD, heart failure and asthma utilisation in outpatient and inpatient settings increased. Multivariate regression indicates higher probability of inpatient admission for males, older patient and especially those with multimorbidity, but protective effect for PHC, with significantly lower hospital admission for those utilising PHC services.InterpretationOur findings suggest health system reforms in Estonia have influenced the shift of ACSCs from secondary to primary care, with PHC having a protective effect in reducing hospital admissions.