Tn1546 is part of a larger plasmid-encoded genetic unit horizontally disseminated among clonal Enterococcus faecium lineages

o determine the genetic composition of the first VanA-type plasmid (pIP816) reported, which was isolated from a clinical Enterococcus faecium (BM4147) strain in France in 1986, and to reveal the genetic units responsible for the dissemination of the vanA gene cluster by comparisons with current, published and additionally generated vanA-spanning plasmid sequences obtained from a heterogeneous E. faecium strain collection (n = 28).Plasmid sequences were produced by shotgun sequencing using ABI dye chemistry and primer walking, and were subsequently annotated. Comparative sequence analysis of the vanA region was done with published plasmids, with a partial vanA plasmid (pVEF4) reported here and to >140 kb of sequence obtained from a collection of vanA-harbouring plasmid fragments. Bioinformatic analyses revealed that pIP816 from 1986 and contemporary vanA plasmids shared a conserved genetic fragment of 25 kb, spanning the 10.85 kb vanA cluster encoded by Tn1546, and that the larger unit is present in both clinical and animal complexes of E. faecium. A new group II intron in pVEF4 was characterized. Comparative DNA analyses suggest that Tn1546 disseminates in and between clonal complexes of E. faecium as part of a larger genetic unit, possibly as a composite transposon flanked by IS1216 elements

NM23 proteins: innocent bystanders or local energy boosters for CFTR?

NM23 proteins NDPK-A and -B bind to the cystic fibrosis (CF) protein CFTR in different ways from kinases such as PKA, CK2 and AMPK or linkers to cell calcium such as calmodulin and annexins. NDPK-A (not -B) interacts with CFTR through reciprocal AMPK binding/control, whereas NDPK-B (not -A) binds directly to CFTR. NDPK-B can activate G proteins without ligand-receptor coupling, so perhaps NDPK-B's binding influences energy supply local to a nucleotide-binding site (NBD1) needed for CFTR to function. Curiously, CFTR (ABC-C7) is a member of the ATP-binding cassette (ABC) protein family that does not obey 'clan rules'; CFTR channels anions and is not a pump, regulates disparate processes, is itself regulated by multiple means and is so pleiotropic that it acts as a hub that orchestrates calcium signaling through its consorts such as calmodulin/annexins. Furthermore, its multiple partners make CFTR dance to different tunes in different cellular and subcellular locations as it recycles from the plasma membrane to endosomes. CFTR function in airway apical membranes is inhibited by smoking which has been dubbed 'acquired CF'. CFTR alone among family members possesses a trap for other proteins that it unfurls as a 'fish-net' and which bears consensus phosphorylation sites for many protein kinases, with PKA being the most canonical. Recently, the site of CFTR's commonest mutation has been proposed as a knock-in mutant that alters allosteric control of kinase CK2 by log orders of activity towards calmodulin and other substrates after CFTR fragmentation. This link from CK2 to calmodulin that binds the R region invokes molecular paths that control lumen formation, which is incomplete in the tracheas of some CF-affected babies. Thus, we are poised to understand the many roles of NDPK-A and -B in CFTR function and, especially lumen formation, which is defective in the gut and lungs of many CF babies

Epidemiology of methicillin-resistant Staphylococcus aureus carrying the novel mecC gene in Denmark corroborates a zoonotic reservoir with transmission to humans

AbstractMethicillin-resistant Staphylococcus aureus (MRSA) is a major cause of healthcare-associated (HA), community-associated (CA) and live-stock-associated (LA) infections. Recently, the discovery of human and bovine MRSA isolates carrying a new mecA gene homologue, mecALGA251 (now designated mecC), has caused concern because they are not detected by conventional, confirmatory tests for MRSA. Very little is known about their frequency, epidemiology and possible transmission between livestock and humans. In this study, the epidemiology of the mecC isolates in Denmark was investigated by screening the national collections of MRSA cases (from 1988 onwards) and S. aureus bacteraemia cases (from 1958 onwards). Isolates carrying mecC were only recovered infrequently before 2003 (n = 2) but now seem to be increasing, with 110 cases in 2003–2011. Clinical data on mecC-carrying MRSA demonstrated that mecC-MRSA were primarily community-acquired (CA-MRSA) and affected persons typically living in rural areas, being older than other CA-MRSA patients. Among 22 cases in Region Zealand, four reported contact with cattle and sheep. Two of these persons lived on farms with livestock positive for mecC-carrying MRSA, sharing spa type (t843), MLVA (MT429) and PFGE pattern with the human isolates. These observations indicate that mecC-carrying MRSA can be exchanged between humans and ruminants

π−p\pi^{-}p and K−pK^{-}p elastic scattering at 6.2 GeV/c

Data on 6.2 GeV/c pi /sup -/p and K/sup -/p elastic scattering cross sections are presented in the range 0.3<-t<10.7 (GeV/c)/sup 2/. Large- angle pi /sup -/p scattering differential cross sections oscillate around an average differential cross section of 50 nb/(GeV/c)/sup 2/, with minima at cos theta /sub cm/ approximately=0 and -0.4. The well- known dip at -t=2.8 (GeV/c)/sup 2/ remains constant in t. In the backward direction there is a dip at -u approximately=1 (GeV/c)/sup 2 /. K/sup -/p elastic scattering has a diffraction peak with a slope of 7.30+or-0.08 (GeV/c)/sup -2/ in the region 0.3<-t<0.6 (GeV/c)/sup 2/. The structure at about -t=1 (GeV/c)/sup 2/ is less pronounced than at 5 GeV/c. The large-angle region is characterized by a very fast decrease of the differential cross section with increasing energy. (67 refs)

Europeanized, Marketized but Still Governed by the State? Private Health Insurance in France

Historically, private health insurance (PHI) in France (which covers the complementary share of health expenditures) has been dominated by non-profit entities, namely mutual benefit societies. The sector has experienced a manifold marketization process over the recent years, partly due to the application of EU law and regulation. Yet this chapter argues that it has been decisively reinforced and sometimes shaped by a series of policies adopted at the national level. Indeed, over the last 20 years, successive French governments have tried to increase health coverage without increasing the share already covered by the public purse. This strategy ostensibly involved private health insurers in achieving several governmental objectives, yet the prior effects of Europeanization on these entities were poorly acknowledged by policymakers. As such, the many consequences associated with the rise of a “European-driven” market now increasingly conflict with a “State-driven” market. This, in turn, has strong implications for the scope and the nature of health coverage