A homologue of aliB is found in the capsule region of nonencapsulated Streptococcus pneumoniae

The epidemiology, phylogeny, and biology of nonencapsulated Streptococcus pneumoniae are largely unknown. Increased colonization capacity and transformability are, however, intriguing features of these pneumococci and play an important role. Twenty-seven nonencapsulated pneumococci were identified in a nationwide collection of 1,980 nasopharyngeal samples and 215 blood samples obtained between 1998 and 2002. On the basis of multilocus sequence typing and capsule region analysis we divided the nonencapsulated pneumococci into two groups. Group I was closely related to encapsulated strains. Group II had a clonal population structure, including two geographically widespread clones able to cause epidemic conjunctivitis and invasive diseases. Group II strains also carried a 1,959-bp homologue of aliB (aliB-like ORF 2) in the capsule region, which was highly homologous to a sequence in the capsule region of Streptococcus mitis. In addition, strains of the two major clones in group II had an additional sequence, aliB-like ORF 1 (1,968 to 2,004 bp), upstream of aliB-like ORF 2. Expression of aliB-like ORF 1 was detected by reverse transcription-PCR, and the corresponding RNA was visualized by Northern blotting. A gene fragment homologous to capN of serotypes 33 and 37 suggests that group II strains were derived from encapsulated pneumococci some time ago. Therefore, loss of capsule expression in vivo was found to be associated with the importation of one or two aliB homologues in some nonencapsulated pneumococci.

Conserved leucine residue in the head region of morbillivirus fusion protein regulates the large conformational change during fusion activity

Paramyxovirus cell entry is controlled by the concerted action of two viral envelope glycoproteins, the fusion (F) and the receptor-binding (H) proteins, which together with a cell surface receptor mediate plasma membrane fusion activity. The paramyxovirus F protein belongs to class I viral fusion proteins which typically contain two heptad repeat regions (HR). Particular to paramyxovirus F proteins is a long intervening sequence (IS) located between both HR domains. To investigate the role of the IS domain in regulating fusogenicity, we mutated in the canine distemper virus (CDV) F protein IS domain a highly conserved leucine residue (L372) previously reported to cause a hyperfusogenic phenotype. Beside one F mutant, which elicited significant defects in processing, transport competence, and fusogenicity, all remaining mutants were characterized by enhanced fusion activity despite normal or slightly impaired processing and cell surface targeting. Using anti-CDV-F monoclonal antibodies, modified conformational F states were detected in F mutants compared to the parental protein. Despite these structural differences, coimmunoprecipitation assays did not reveal any drastic modulation in F/H avidity of interaction. However, we found that F mutants had significantly enhanced fusogenicity at low temperature only, suggesting that they folded into conformations requiring less energy to activate fusion. Together, these data provide strong biochemical and functional evidence that the conserved leucine 372 at the base of the HRA coiled-coil of F(wt) controls the stabilization of the prefusogenic state, restraining the conformational switch and thereby preventing extensive cell-cell fusion activity.

Phase diagram with an enhanced spin-glass region of the mixed Ising–XY magnet LiHo{x}Er{1-x}F{4}

We present the experimental phase diagram of LiHoxEr1-xF4, a dilution series of dipolar-coupled model magnets. The phase diagram was determined using a combination of ac susceptibility and neutron scattering. Three unique phases in addition to the Ising ferromagnet LiHoF4 and the XY antiferromagnet LiErF4 have been identified. Below x = 0.86, an embedded spin-glass phase is observed, where a spin glass exists within the ferromagnetic structure. Below x = 0.57, an Ising spin glass is observed consisting of frozen needlelike clusters. For x ∼ 0.3–0.1, an antiferromagnetically coupled spin glass occurs. A reduction of TC(x) for the ferromagnet is observed which disobeys the mean-field predictions that worked for LiHoxY1-xF4.

Structural rearrangements of the central region of the morbillivirus attachment protein stalk domain trigger F protein refolding for membrane fusion

It is unknown how receptor binding by the paramyxovirus attachment proteins (HN, H, or G) triggers the fusion (F) protein to fuse with the plasma membrane for cell entry. H-proteins of the morbillivirus genus consist of a stalk ectodomain supporting a cuboidal head; physiological oligomers consist of non-covalent dimer-of-dimers. We report here the successful engineering of intermolecular disulfide bonds within the central region (residues 91-115) of the morbillivirus H-stalk; a sub-domain that also encompasses the putative F-contacting section (residues 111-118). Remarkably, several intersubunit crosslinks abrogated membrane fusion, but bioactivity was restored under reducing conditions. This phenotype extended equally to H proteins derived from virulent and attenuated morbillivirus strains and was independent of the nature of the contacted receptor. Our data reveal that the morbillivirus H-stalk domain is composed of four tightly-packed subunits. Upon receptor binding, these subunits structurally rearrange, possibly inducing conformational changes within the central region of the stalk, which, in turn, promote fusion. Given that the fundamental architecture appears conserved among paramyxovirus attachment protein stalk domains, we predict that these motions may act as a universal paramyxovirus F-triggering mechanism.

Cloning, sequencing and partial functional characterization of the 5' region of the human p75 tumor necrosis factor receptor-encoding gene (TNF-R)

A 1887-bp region at the 5' flank of the human p75 tumor necrosis factor receptor (p75 TNF-R)-encoding gene was found to be active in driving expression of the luc (luciferase-encoding) reporter gene, suggesting that it contains the promoter for the receptor. Rather unexpectedly, a 1827-bp region at the 3' end of the first intron of the p75 TNF-R gene also displayed promoter activity. This activity may be artefactual, reflecting only the presence of an enhancer in this region; yet it also raises the possibility that p75 TNF-R is controlled by more than one promoter and that it encodes various forms of the receptor, or even other proteins. We present here the nucleotide sequences of the 5' flanking and intron regions. Possible implications for the transcriptional regulation of the p75 TNF-R gene are discussed.

Possible open-system (hydraulic) pingos in and around the Argyre impact region of Mars

We report the observation of possible (hydraulic) open-system pingos (OSPs ) at the mid latitudes (∼37°S) in and around the Argyre impact-basin. OSPs are perennial (water)–ice cored mounds; they originate and evolve in periglacial and pro-glacial landscapes on Earth where intra- or sub-permafrost water under hydraulic/artesian pressure uplifts localised sections of surface or near-surface permafrost that then freezes in-situ. We invoke three lines of evidence in support of our analogue-based interpretation: (1) similarities of shape, size and summit traits between terrestrial OSPs and the Martian mounds; (2) clustered distribution and the slope-side location of the mounds, consistent with terrestrial permafrost-environments where OSPs are found; and, (3) spatially-associated landforms putatively indicative of periglacial and glacial processes on Mars that characterise OSP landscapes on Earth. This article presents five OSP candidate-locations and nests these mound locations within a new geological map of the Argyre impact-basin and margins. It also presents three periglacial hypotheses about the possible origin of the water required to develop the mounds. Alternative (non-periglacial) formation-hypotheses also are considered; however, we show that their robustness is not equal to that of the periglacial ones.

Preconceptional use of folic acid in the region of the Kantonsspital Münsterlingen/Thurgau: has it changed over the past 10 years?

BACKGROUND  Numerous studies have shown that the preconceptional use of folic acid prevents neural tube defects. We created a study to find out whether the preconceptional use of folic acid has improved in the past 10 years, in the area of Münsterlingen, Switzerland. MATERIAL AND METHODS  We interviewed 2 groups of patients who delivered at our Institution, namely between 2000 and 2002 (period A) involving 287 women and from 2009 to 2010 (period B) involving 305 pregnant women. We asked them whether they used folic acid by means of a standardised questionnaire. RESULTS  In period B significantly more women have taken folic acid preconceptionally (period A: 27.5% vs. period B: 40.7%; p=0.001). A significant increase in folic acid intake was seen in the German speaking group from period A to B (30.3% vs. 52.7%; p=0.0005), while this was not the case in the non-German speaking group (21.4% in both periods). More multiparaé women were taking folic acid compared to nulliparae. A significant increase from period A to B was noted only in the German speaking group. Unexpectedly, in nulliparae non-German speaking women, folic acid supplementation decreased from 14% to 6.1%. DISCUSSION  We have found a significant increase in preconceptional folic acid supplementation from 2001 to 2010. The percentage of women taking folic acid is disappointingly low in all groups, particularly in nulliparae women of non-German ethnicity.