MR assessment of fetal lung development using lung volumes and signal intensities

The purpose of this study was to evaluate the monitoring and diagnostic potential of MRI in fetal lung development and disease using lung volume and signal intensity changes through gestation. Thirty-five healthy fetuses (22-42weeks) were examined on a 1.5-T MR system using sagittal T2w single-shot fast spin-echo imaging (TR indefinite, TE 90ms, slice thickness/gap 3-5/0mm, FOV 26-40cm, NEX 0.5). Fetal body and lung were segmented manually and volumes calculated. Signal intensities (SI) of fetal lung and three reference values were measured on the section best displaying the lung. Regions of interests were defined by including the maximal organ area possible. The following SI ratios were generated: lung/liver, lung/amniotic fluid, lung/muscle, liver/fluid and liver/muscle. Volumes and ratios were correlated with gestational age. Data from seven fetuses with pulmonary pathology were compared with these normative values. Absolute lung volume varied from 12.3 to 143.5cm3 in correlation with gestational age (P<0.001); lung volume relative to total body volume ranged from 1.6 to 5.0%, decreasing with gestational age (P=0.001). All SI ratios measured were unrelated to gestational age. Diagnoses in the seven abnormal fetuses were hydrothorax (n=2), congenital cystic adenomatoid malformation (n=2), diaphragmatic hernia (n=2) and pulmonary sequestration (n=1); their absolute and relative lung volumes were below normal (P<0.001). The SI ratios did not differ significantly from those in the normal population. Normative MR fetal lung volumes may have important clinical applications in confirming and quantifying intrauterine pulmonary hypoplasia and in complementing ultrasound in the planning of fetal and post-natal surgery. No clinical relevance was found for fetal lung SI value

The phase transition phenomena in anisotropic superconductors: effect of the orthorhombic crystal field and the potential impurity scattering

A combined effect of the orthorhombic crystal field and potential impurity scattering on several superconducting states of a tetragonal symmetry is studied within a weak-coupling mean field approach. It is shown that the nonmagnetic impurities stabilize the states belonging to the identity irreducible representation. The electronic specific heat jump at the phase transition is analyzed. Its dependence on the potential scattering rate for large impurity concentration is shown to be remarkably different for the states with a nonzero value of the Fermi surface averaged order parameter than for those with a vanishing one. In particular, very distinct signals from d_{x^2-y^2} state in YBCO and d_{xy} state in BSCCO compound are predicted. This effect may be used as a test for the presence of these states in the above cuprates.Comment: 21 pages, 2 tables, RevTex, 12 PostScript figure

Analysis of Prototype Foamy Virus particle-host cell interaction with autofluorescent retroviral particles

<p>Abstract</p> <p>Background</p> <p>The foamy virus (FV) replication cycle displays several unique features, which set them apart from orthoretroviruses. First, like other B/D type orthoretroviruses, FV capsids preassemble at the centrosome, but more similar to hepadnaviruses, FV budding is strictly dependent on cognate viral glycoprotein coexpression. Second, the unusually broad host range of FV is thought to be due to use of a very common entry receptor present on host cell plasma membranes, because all cell lines tested in vitro so far are permissive.</p> <p>Results</p> <p>In order to take advantage of modern fluorescent microscopy techniques to study FV replication, we have created FV Gag proteins bearing a variety of protein tags and evaluated these for their ability to support various steps of FV replication. Addition of even small N-terminal HA-tags to FV Gag severely impaired FV particle release. For example, release was completely abrogated by an N-terminal autofluorescent protein (AFP) fusion, despite apparently normal intracellular capsid assembly. In contrast, C-terminal Gag-tags had only minor effects on particle assembly, egress and particle morphogenesis. The infectivity of C-terminal capsid-tagged FV vector particles was reduced up to 100-fold in comparison to wild type; however, infectivity was rescued by coexpression of wild type Gag and assembly of mixed particles. Specific dose-dependent binding of fluorescent FV particles to target cells was demonstrated in an Env-dependent manner, but not binding to target cell-extracted- or synthetic- lipids. Screening of target cells of various origins resulted in the identification of two cell lines, a human erythroid precursor- and a zebrafish- cell line, resistant to FV Env-mediated FV- and HIV-vector transduction.</p> <p>Conclusions</p> <p>We have established functional, autofluorescent foamy viral particles as a valuable new tool to study FV - host cell interactions using modern fluorescent imaging techniques. Furthermore, we succeeded for the first time in identifying two cell lines resistant to Prototype Foamy Virus Env-mediated gene transfer. Interestingly, both cell lines still displayed FV Env-dependent attachment of fluorescent retroviral particles, implying a post-binding block potentially due to lack of putative FV entry cofactors. These cell lines might ultimately lead to the identification of the currently unknown ubiquitous cellular entry receptor(s) of FVs.</p

Ginzburg-Landau theory of superconductors with short coherence length

We consider Fermions in two dimensions with an attractive interaction in the singlet d-wave channel of arbitrary strength. By means of a Hubbard-Stratonovich transformation a statistical Ginzburg-Landau theory is derived, which describes the smooth crossover from a weak-coupling BCS superconductor to a condensate of composite Bosons. Adjusting the interaction strength to the observed slope of H_c2 at T_c in the optimally doped high-T_c compounds YBCO and BSCCO, we determine the associated values of the Ginzburg-Landau correlation length xi and the London penetration depth lambda. The resulting dimensionless ratio k_F xi(0) approx 5-8 and the Ginzburg-Landau parameter kappa=lambda xi approx 90-100 agree well with the experimentally observed values. These parameters indicate that the optimally doped materials are still on the weak coupling side of the crossover to a Bose regime.Comment: 12 pages, RevTeX, 6 postscript figures, resubmitted with minor changes in section III, to appear in Physical Review

Structured bimanual actions and hand transfers reveal population-level right-handedness in captive gorillas

There is a common prevailing perception that humans possess a species-unique population-level right-hand bias that has evolutionary links with language. New theories suggest that an early evolutionary division of cognitive function gave rise to a left-hemisphere bias for behaviours underpinned by structured sequences of actions. However, studies of great ape handedness have generated inconsistent results and considerable debate. Additionally, the literature places a heavy focus on chimpanzees, revealing a paucity of handedness findings from other great ape species, and thus limiting the empirical evidence with which we can evaluate evolutionary theory. We observed handedness during spontaneous naturalistic bimanual actions in a captive, biological group of 13 western lowland gorillas, Gorilla gorilla gorilla. Our results demonstrated a significant group-level right-handed bias for bimanual actions as well as for a novel measure of handedness: hand transfer. The two measures revealed similar patterns of handedness, such that a right-hand bias for the majority of individuals was found across both measures. Our findings suggest that human population-level right-handedness is a behavioural trait linked with left-hemisphere dominance for the processing of structured sequences of actions, and was inherited by a common ancestor of both humans and apes

Alternative Splicing of the Cardiac Sodium Channel Creates Multiple Variants of Mutant T1620K Channels

Alternative splicing creates several Nav1.5 transcripts in the mammalian myocardium and in various other tissues including brain, dorsal root ganglia, breast cancer cells as well as neuronal stem cell lines. In total nine Nav1.5 splice variants have been discovered. Four of them, namely Nav1.5a, Nav1.5c, Nav1.5d, and Nav1.5e, generate functional channels in heterologous expression systems. The significance of alternatively spliced transcripts for cardiac excitation, in particular their role in SCN5A channelopathies, is less well understood. In the present study, we systematically investigated electrophysiological properties of mutant T1620K channels in the background of all known functional Nav1.5 splice variants in HEK293 cells. This mutation has been previously associated with two distinct cardiac excitation disorders: with long QT syndrome type 3 (LQT3) and isolated cardiac conduction disease (CCD). When investigating the effect of the T1620K mutation, we noticed similar channel defects in the background of hNav1.5, hNav1.5a, and hNav1.5c. In contrast, the hNav1.5d background produced differential effects: In the mutant channel, some gain-of-function features did not emerge, whereas loss-of-function became more pronounced. In case of hNav1.5e, the neonatal variant of hNav1.5, both the splice variant itself as well as the corresponding mutant channel showed electrophysiological properties that were distinct from the wild-type and mutant reference channels, hNav1.5 and T1620K, respectively. In conclusion, our data show that alternative splicing is a mechanism capable of generating a variety of functionally distinct wild-type and mutant hNav1.5 channels. Thus, the cellular splicing machinery is a potential player affecting genotype-phenotype correlations in SCN5A channelopathies

Recommendations for early referral of individuals with suspected polymyalgia rheumatica: An initiative from the international giant cell arteritis and polymyalgia rheumatica study group

Objective To develop international consensus-based recommendations for early referral of individuals with suspected polymyalgia rheumatica (PMR). Methods A task force including 29 rheumatologists/ internists, 4 general practitioners, 4 patients and a healthcare professional emerged from the international giant cell arteritis and PMR study group. The task force supplied clinical questions, subsequently transformed into Population, Intervention, Comparator, Outcome format. A systematic literature review was conducted followed by online meetings to formulate and vote on final recommendations. Levels of evidence (LOE) (1–5 scale) and agreement (LOA) (0–10 scale) were evaluated. Results Two overarching principles and five recommendations were developed. LOE was 4–5 and LOA ranged between 8.5 and 9.7. The recommendations suggest that (1) each individual with suspected or recently diagnosed PMR should be considered for specialist evaluation, (2) before referring an individual with suspected PMR to specialist care, a thorough history and clinical examination should be performed and preferably complemented with urgent basic laboratory investigations, (3) individuals with suspected PMR with severe symptoms should be referred for specialist evaluation using rapid access strategies, (4) in individuals with suspected PMR who are referred via rapid access, the commencement of glucocorticoid therapy should be deferred until after specialist evaluation and (5) individuals diagnosed with PMR in specialist care with a good initial response to glucocorticoids and a low risk of glucocorticoid related adverse events can be managed in primary care. Conclusions These are the first international recommendations for referral of individuals with suspected PMR, which complement the European Alliance of Associations for Rheumatology/American College of Rheumatology management guidelines for established PMR