CO J=2-1 line emission in cluster galaxies at z~1: fueling star formation in dense environments

We present observations of CO J=2-1 line emission in infrared-luminous cluster galaxies at z~1 using the IRAM Plateau de Bure Interferometer. Our two primary targets are optically faint, dust-obscured galaxies (DOGs) found to lie within 2 Mpc of the centers of two massive (>10^14 Msun) galaxy clusters. CO line emission is not detected in either DOG. We calculate 3-sigma upper limits to the CO J=2-1 line luminosities, L'_CO < 6.08x10^9 and < 6.63x10^9 K km/s pc^2. Assuming a CO-to-H_2 conversion factor derived for ultraluminous infrared galaxies in the local Universe, this translates to limits on the cold molecular gas mass of M_H_2 < 4.86x10^9 Msun and M_H_2 < 5.30x10^9 Msun. Both DOGs exhibit mid-infrared continuum emission that follows a power-law, suggesting that an AGN contributes to the dust heating. As such, estimates of the star formation efficiencies in these DOGs are uncertain. A third cluster member with an infrared luminosity, L_IR < 7.4x10^11 Lsun, is serendipitously detected in CO J=2-1 line emission in the field of one of the DOGs located roughly two virial radii away from the cluster center. The optical spectrum of this object suggests that it is likely an obscured AGN, and the measured CO line luminosity is L'_CO = (1.94 +/- 0.35)x10^10 K km/s pc^2, which leads to an estimated cold molecular gas mass M_H_2 = (1.55+/-0.28)x10^10 Msun. A significant reservoir of molecular gas in a z~1 galaxy located away from the cluster center demonstrates that the fuel can exist to drive an increase in star-formation and AGN activity at the outskirts of high-redshift clusters.Comment: 22 pages, 4 figures; accepted for publication in Ap

Relationship between changes in motor capacity and objectively measured motor performance in ambulatory children with spastic cerebral palsy

Background: Different interventions are offered to children with cerebral palsy (CP) to improve the activity domain of the international classification of functioning (ICF). In therapy settings, the focus is mostly on motor capacity, but the ultimate goal is to improve motor performance. We therefore examined if changes in motor capacity outcomes are accompanied by changes in objectively measured motor performance after a 3-month intensive treatment period in ambulatory children with CP. Methods: A secondary analysis on prospective clinical trial data was performed using multivariate linear regression. Sixty-five children (37 boys and 28 girls) with spastic CP, mean age 7 years and 3 months, Gross Motor Function Classification System (GMFCS) levels I–III were involved in a distinct 3-month intensive treatment period. Motor capacity (Gross Motor Function Measure [GMFM], functional muscle strength [FMS], and walking speed [WS]) and motor performance (using three Actigraph-GT3X+-derived outcome measures) were measured at baseline, 12 and 24 weeks. Results: No significant associations were found for any of the change scores (∆12) between motor capacity and motor performance after a 12-week intensive treatment period. After 24 weeks, ∆24FMS (p =.042) and ∆24WS (p =.036) were significantly associated with changes in motor performance outcome measure percentage of time spent sedentary (∆24%sedentary). In this model, 16% of variance of ∆24%sedentary was explained by changes in motor capacity (p =.030). Conclusions: Changes in motor capacity are mostly not accompanied by changes in objectively measured motor performance after an intensive treatment period for ambulatory children with CP. These findings should be taken into account during goal setting and are important to manage expectations of both short- and longer term effects of treatment programmes

Directly observed antiretroviral therapy: a systematic review and meta-analysis of randomised clinical trials.

BACKGROUND: Directly observed therapy has been recommended to improve adherence for patients with HIV infection who are on highly active antiretroviral therapy, but the benefit and cost-effectiveness of this approach has not been established conclusively. We did a systematic review and meta-analysis of randomised trials of directly observed versus self-administered antiretroviral treatment. METHODS: We did duplicate searches of databases (from inception to July 27, 2009), searchable websites of major HIV conferences (up to July, 2009), and lay publications and websites (March-July, 2009) to identify randomised trials assessing directly observed therapy to promote adherence to antiretroviral therapy in adults. Our primary outcome was virological suppression at study completion. We calculated relative risks (95% CIs), and pooled estimates using a random-effects method. FINDINGS: 12 studies met our inclusion criteria; four of these were done in groups that were judged to be at high risk of poor adherence (drug users and homeless people). Ten studies reported on the primary outcome (n=1862 participants); we calculated a pooled relative risk of 1.04 (95% CI 0.91-1.20, p=0.55), and noted moderate heterogeneity between the studies (I(2)= 53.8%, 95% CI 0-75.7, p=0.0247) for directly observed versus self-administered treatment. INTERPRETATION: Directly observed antiretroviral therapy seems to offer no benefit over self-administered treatment, which calls into question the use of such an approach to support adherence in the general patient population. FUNDING: None

New Approaches to Olefin Cross-Metathesis

New methodology for the selective cross-metathesis (CM) of terminal olefins employing ruthenium benzylidene 1 is described.1 CM with symmetric internal olefins was found to provide a useful means for homologating terminal olefins to protected allylic alcohols, amines, and esters. Due to the limited commercial availability of symmetric internal olefins, a two-step CM procedure was developed in which terminal olefins were first homodimerized prior to the CM reaction. Terminal olefins with allylic methyl substituents were observed to provide CM products in diminished yield albeit with markedly improved trans-selectivity. Reaction rates were measured for CM reactions utilizing butenediol and allyl alcohol derivatives, and the results demonstrated distinct advantages in reaction rate and stereoselectivity for reactions employing the disubstituted olefins. In the course of studies of substrates with allylic oxygen substituents, a new CM application was discovered involving the metathesis of acrolein acetal derivatives with terminal olefins. Acrolein acetals, including asymmetric variants derived from tartaric acid, proved to be exceptionally robust and trans-selective CM substrates. In related work, a pinacol-derived vinyl boronate was also found to be a reactive CM partner, providing a novel means for converting terminal olefins into precursors for the Suzuki coupling reaction

Plant and fungal use in Tusheti, Khevsureti, and Pshavi, Sakartvelo (Republic of Georgia), Caucasus

In this study, we documented traditional plant use in Tusheti, Khevsureti, and Pshavi and hypothesized that (i) plant use knowledge in general would be higher in isolated high elevation communities, and that (ii) use of home gardens would be much more restricted to lower elevation settings. Fieldwork was conducted in Khevsureti, Pshavi, and Tusheti. Interviews using semi-structured questionnaires were conducted with 74 participants. In the present study, we encountered 317 plant species belonging to 203 genera of 80 families being used in the research region. Of these, 197 species were exclusively wild-harvested, 73 were grown in homegardens, and 47 were both grown in gardens and sourced in the wild. The ordinations in plant-space and in use-space were significantly fit by elevation of informant community, and community itself. Age and gender did not significantly fit the distribution of informants across either plant-space or use-space, respectively. Number of use-reports was highest across all communities in the food and medicinal use-categories, and informant consensus. Species with especially high use-diversity (UD) tended to be woody species although. Species with high use-value (UV) were mostly managed/domesticated species from home orchards, gardens, or farms. Plant species, and uses, found in our study, showed clear relations to the wider Eurasian cultural complex. The species number found was, however, far higher than in any published study from either the region or the wiser Mediterranean and Eurasia. The maintenance of home gardens in Georgia serves as socio-ecological memory. While the great variety of plant species used in the Georgian Caucasus might provide a reservoir for food security climate change is starting to affect both natural floristic diversity and gardens both in the Caucasus as well as continent wide

Impaired protein translation in Drosophila models for Charcot–Marie–Tooth neuropathy caused by mutant tRNA synthetases

Dominant mutations in five tRNA synthetases cause Charcot–Marie–Tooth (CMT) neuropathy, suggesting that altered aminoacylation function underlies the disease. However, previous studies showed that loss of aminoacylation activity is not required to cause CMT. Here we present a Drosophila model for CMT with mutations in glycyl-tRNA synthetase (GARS). Expression of three CMT-mutant GARS proteins induces defects in motor performance and motor and sensory neuron morphology, and shortens lifespan. Mutant GARS proteins display normal subcellular localization but markedly reduce global protein synthesis in motor and sensory neurons, or when ubiquitously expressed in adults, as revealed by FUNCAT and BONCAT. Translational slowdown is not attributable to altered tRNA[superscript Gly] aminoacylation, and cannot be rescued by Drosophila Gars overexpression, indicating a gain-of-toxic-function mechanism. Expression of CMT-mutant tyrosyl-tRNA synthetase also impairs translation, suggesting a common pathogenic mechanism. Finally, genetic reduction of translation is sufficient to induce CMT-like phenotypes, indicating a causal contribution of translational slowdown to CMT.National Institutes of Health (U.S.) (Grant GM17151

Zebrafish prox1b Mutants Develop a Lymphatic Vasculature, and prox1b Does Not Specifically Mark Lymphatic Endothelial Cells

Background: The expression of the Prospero homeodomain transcription factor (Prox1) in a subset of cardinal venous cells specifies the lymphatic lineage in mice. Prox1 is also indispensible for the maintenance of lymphatic cell fate, and is therefore considered a master control gene for lymphangiogenesis in mammals. In zebrafish, there are two prox1 paralogues, the previously described prox1 (also known as prox1a) and the newly identified prox1b. Principal Findings: To investigate the role of the prox1b gene in zebrafish lymphangiogenesis, we knocked-down prox1b and found that depletion of prox1b mRNA did not cause lymphatic defects. We also generated two different prox1b mutant alleles, and maternal-zygotic homozygous mutant embryos were viable and did not show any lymphatic defects. Furthermore, the expression of prox1b was not restricted to lymphatic vessels during zebrafish development. Conclusion: We conclude that Prox1b activity is not essential for embryonic lymphatic development in zebrafish

Intramuscular botulinum toxin prior to comprehensive rehabilitation has no added value for improving motor impairments, gait kinematics and goal attainment in walking children with spastic cerebral palsy

Objective: Botulinum toxin (BoNT-A) is widely used in combined treatment for spastic cerebral palsy, but its added value preceding comprehensive rehabilitation for motor impairments, gait, and goal attainment has not been studied. Design: A comparative multi-centre trial, in which two groups underwent comprehensive rehabilitation (i.e. high-intensive functional physiotherapy, and indicated casting/orthoses). One group received intramuscular BoNT-A prior to rehabilitation, and the other group did not receive BoNT-A. Subjects/patients: Children with spastic cerebral palsy, Gross Motor Function Classification System (GMFCS) levels I–III, age range 4–12 years, indicated for BoNT-A treatment regarding mobility problems. Methods: Sixty-five children participated (37 boys), mean age 7.3 years (standard deviation (SD) 2.3, range 4–12 years), equally distributed across GMFCS levels. Forty-one children received BoNT-A+ comprehensive rehabilitation and 24 received comprehensive rehabilitation only. Functional leg muscle strength, passive range of motion, angle of catch, cer

Hedgehog signaling via a calcitonin receptor-like receptor can induce arterial differentiation independently of VEGF signaling in zebrafish

Multiple signaling pathways control the specification of endothelial cells (ECs) to become arteries or veins during vertebrate embryogenesis. Current models propose that a cascade of Hedgehog (Hh), vascular endothelial growth factor (VEGF), and Notch signaling acts instructively on ECs to control the choice between arterial or venous fate. Differences in the phenotypes induced by Hh, VEGF, or Notch inhibition suggest that not all of the effects of Hh on arteriovenous specification are mediated by VEGF. We establish that full derepression of the Hh pathway in ptc1;ptc2 mutants converts the posterior cardinal vein into a second arterial vessel that manifests intact arterial gene expression, intersegmental vessel sprouting, and HSC gene expression. Importantly, although VEGF was thought to be absolutely essential for arterial fates, we find that normal and ectopic arterial differentiation can occur without VEGF signaling in ptc1;ptc2 mutants. Furthermore, Hh is able to bypass VEGF to induce arterial differentiation in ECs via the calcitonin receptor-like receptor, thus revealing a surprising complexity in the interplay between Hh and VEGF signaling during arteriovenous specification. Finally, our experiments establish a dual function of Hh during induction of runx1+ HSCs