The rate of CD4 decline as a determinant of progression to AIDS independent of the most recent CD4 count

The data of two cohort studies of HIV-infected individuals were used to examine whether the rate of CD4 decline is a determinant of HIV progression, independent of the most recent CD4 count. Time from seroconversion to clinical AIDS was the main outcome measure. Rates of CD4 decline were estimated using the ordinary least squares regression method. AIDS incidences were compared in individuals who had previously experienced either a steeper or a less steep rate of CD4 decline. Cox proportional hazards model including a time-dependent covariate for the rate of CD4 decline was performed. The rate of prior CD4 decline was significantly associated with the risk of developing AIDS independently from the most recent CD4 count, with a 2 % increase in hazard of AIDS (P < 0.01) for a difference of 10 cells/mm(3) in the estimated yearly drop in CD4 count. This finding gives scientific credit to the belief that individuals with a prior steeper CD4 decline consistently have a higher subsequent risk of developing AIDS than those with a less steep prior decline

Nuclear hyaluronidase 2 drives alternative splicing of CD44 pre-mRNA to determine profibrotic or antifibrotic cell phenotype.

This is the author accepted manuscript. The final version is available from American Association for the Advancement of Science via the DOI in this record.The cell surface protein CD44 is involved in diverse physiological processes, and its aberrant function is linked to various pathologies such as cancer, immune dysregulation, and fibrosis. The diversity of CD44 biological activity is partly conferred by the generation of distinct CD44 isoforms through alternative splicing. We identified an unexpected function for the ubiquitous hyaluronan-degrading enzyme, hyaluronidase 2 (HYAL2), as a regulator of CD44 splicing. Standard CD44 is associated with fibrotic disease, and its production is promoted through serine-arginine-rich (SR) protein-mediated exon exclusion. HYAL2 nuclear translocation was stimulated by bone morphogenetic protein 7, which inhibits the myofibroblast phenotype. Nuclear HYAL2 displaced SR proteins from the spliceosome, thus enabling HYAL2, spliceosome components (U1 and U2 small nuclear ribonucleoproteins), and CD44 pre-mRNA to form a complex. This prevented double-exon splicing and facilitated the inclusion of CD44 exons 11 and 12, which promoted the accumulation of the antifibrotic CD44 isoform CD44v7/8 at the cell surface. These data demonstrate previously undescribed mechanisms regulating CD44 alternative splicing events that are relevant to the regulation of cellular phenotypes in progressive fibrosis.Medical Research Counci

Taxonomic distinctness in the diet of two sympatric marine turtle species

Marine turtles are considered keystone consumers in tropical coastal ecosystems and their decline through overexploitation has been implicated in the deterioration of reefs and seagrass pastures in the Caribbean. In the present study, we analysed stomach contents of green (Chelonia mydas) and hawksbill turtles (Eretmochelys imbricata) harvested in the legal turtle fishery of the Turks and Caicos Islands (Caribbean) during 2008–2010. Small juveniles to adult-sized turtles were sampled. Together with data from habitat surveys, we assessed diet composition and the taxonomic distinctness (and other species diversity measures) in the diets of these sympatric marine turtle species. The diet of green turtles (n = 92) consisted of a total of 47 taxa: including three species of seagrass (present in 99% of individuals), 29 species of algae and eight sponge species. Hawksbill turtles (n = 45) consumed 73 taxa and were largely spongivorous (16 species; sponges present in 100% of individuals) but also foraged on 50 species of algae (present in 73% of individuals) and three species of seagrass. Plastics were found in trace amounts in 4% of green turtle and 9% of hawksbill turtle stomach samples. We expected to find changes in diet that might reflect ontogenetic shifts from small (oceanic-pelagic) turtles to larger (coastal-benthic) turtles. Dietary composition (abundance and biomass), however, did not change significantly with turtle size, although average taxonomic distinctness was lower in larger green turtles. There was little overlap in prey between the two turtle species, suggesting niche separation. Taxonomic distinctness routines indicated that green turtles had the most selective diet, whereas hawksbill turtles were less selective than expected when compared with the relative frequency and biomass of diet items. We discuss these findings in relation to the likely important trophic roles that these sympatric turtle species play in reef and seagrass habitats.This work was funded by Simon & Anne Notley, MCS, and Natural Environment Research Council (CASE PhD studentship to TS with MCS as CASE partners, Ref: NE/F01385X/1)

Identifying barriers to help seeking for non-motor symptoms in people with Parkinson’s disease

Non-motor Symptoms (NMS) of Parkinson’s disease (PD) have a significant impact on quality of life. Despite this many NMS remain unreported by patients and consequently untreated. The present study explored barriers to help-seeking using two theoretical frameworks, the Common Sense Model of illness and Theoretical Domains Framework. 20 Participants completed semi-structured interviews to explore symptom beliefs and help-seeking behaviour. Uncertainty about the relationship of NMS to PD and lack of clarity around treatments were common. Embarrassment and communication difficulties were common for potentially sensitive symptoms such as sexual dysfunction. Symptom perceptions and beliefs about help-seeking acted as barriers to reporting NMS

Tunnelling anisotropic magnetoresistance at La<inf>0.67</inf>Sr<inf>0.33</inf>MnO<inf>3</inf>-graphene interfaces

Using ferromagnetic La0.67Sr0.33MnO3 electrodes bridged by single-layer graphene, we observe magnetoresistive changes of ∼32–35 MΩ at 5 K. Magneto-optical Kerr effect microscopy at the same temperature reveals that the magnetoresistance arises from in-plane reorientations of electrode magnetization, evidencing tunnelling anisotropic magnetoresistance at the La0.67Sr0.33MnO3-graphene interfaces. Large resistance switching without spin transport through the non-magnetic channel could be attractive for graphene-based magnetic-sensing applications.This work was funded by grant F/09 154/E from the Leverhulme Trust, ERC Grant Hetero2D, EU Graphene Flagship (no. 604391), a Schlumberger Cambridge International Scholarship, a UK EPSRC DTA award, the Royal Society, and EPSRC Grants EP/K01711X/1, EP/K017144/1, EP/N010345/1, EP/M507799/1 and EP/L016087/1.This is the author accepted manuscript. The final version is available at http://scitation.aip.org/content/aip/journal/apl/108/11/10.1063/1.4942778

The Neutral ISM in Nearby Luminous Compact Blue Galaxies

We observed 20 nearby Luminous Compact Blue Galaxies (LCBGs) in HI and CO(J=2-1) with the GBT and JCMT. These ~L^star galaxies are blue, high surface brightness, starbursting, high metallicity galaxies with an underlying older stellar population. They are common at z~1, but rare in the local Universe. It has been proposed that intermediate redshift LCBGs may be the progenitors of local dwarf ellipticals or low luminosity spirals, or that they may be more massive disks forming from the center outward to become L^star galaxies. To discriminate among various possible evolutionary scenarios, we have measured the dynamical masses and gas depletion time scales of this sample of nearby LCBGs. We find that local LCBGs span a wide range of dynamical masses, from 4 x 10^9 to 1 x 10^11 M_solar (measured within R_25). Molecular gas in local LCBGs is depleted quite quickly, in 30 to 200 million years. The molecular plus atomic gas is depleted in 30 million to 10 billion years; however, ~80% of the local LCBGs deplete their gas in less than 5 billion years. As LCBGs are heterogeneous in both dynamical mass and gas depletion time scales, they are not likely to evolve into one homogeneous galaxy class.Comment: 4 pages, 2 figures, to be published in 4th Cologne-Bonn-Zermatt-Symposium, Eds. S. Pfalzner, C. Kramer, C. Straubmeier, and A. Heithause

Laser cooling of a diatomic molecule

It has been roughly three decades since laser cooling techniques produced ultracold atoms, leading to rapid advances in a vast array of fields. Unfortunately laser cooling has not yet been extended to molecules because of their complex internal structure. However, this complexity makes molecules potentially useful for many applications. For example, heteronuclear molecules possess permanent electric dipole moments which lead to long-range, tunable, anisotropic dipole-dipole interactions. The combination of the dipole-dipole interaction and the precise control over molecular degrees of freedom possible at ultracold temperatures make ultracold molecules attractive candidates for use in quantum simulation of condensed matter systems and quantum computation. Also ultracold molecules may provide unique opportunities for studying chemical dynamics and for tests of fundamental symmetries. Here we experimentally demonstrate laser cooling of the molecule strontium monofluoride (SrF). Using an optical cycling scheme requiring only three lasers, we have observed both Sisyphus and Doppler cooling forces which have substantially reduced the transverse temperature of a SrF molecular beam. Currently the only technique for producing ultracold molecules is by binding together ultracold alkali atoms through Feshbach resonance or photoassociation. By contrast, different proposed applications for ultracold molecules require a variety of molecular energy-level structures. Our method provides a new route to ultracold temperatures for molecules. In particular it bridges the gap between ultracold temperatures and the ~1 K temperatures attainable with directly cooled molecules (e.g. cryogenic buffer gas cooling or decelerated supersonic beams). Ultimately our technique should enable the production of large samples of molecules at ultracold temperatures for species that are chemically distinct from bialkalis.Comment: 10 pages, 7 figure

Medical Students Educate Teens About Skin Cancer: What Have We Learned?

Skin cancer is a serious societal problem, and public awareness outreach, including to youth, is crucial. Medical students have joined forces to educate adolescents about skin cancer with significant impacts; even one 50-min interactive outreach session led to sustained changes in knowledge and behavior in a cohort of 1,200 adolescents surveyed. Medical students can act as a tremendous asset to health awareness public outreach efforts: enthusiastic volunteerism keeps education cost-effective, results in exponential spread of information, reinforces knowledge and communication skills of future physicians, and can result in tangible, life-saving benefits such as early detection of melanoma

Insulators and imprinting from flies to mammals

The nuclear factor CTCF has been shown to be necessary for the maintenance of genetic imprinting at the mammalian H19/Igf2 locus. MacDonald and colleagues now report in BMC Biology that the mechanisms responsible for maintaining the imprinted state in Drosophila may be evolutionarily conserved and that CTCF may also play a critical role in this process