The exopolyhedral ligand orientation (ELO) in 3-(nitrato-κO)-3,3-bis(triphenylphosphane-κP)-3-rhoda-1,2-dicarba-closo-dodecaborane(11) dichloromethane 2.2-solvate

In the title compound, [Rh(C2H11B9)(NO3)(C18H15P)2]·2.2CH2Cl2, studied as a 2.2-solvate of what was assumed to be dichloromethane, the nitrate ligand liesciswith respect to both cage C atoms. Accordingly, the compound displays a pronounced preferred exopolyhedral ligand orientation (ELO) which is traced to both the greatertransinfluence of the cage B over the cage C atoms and the greatertransinfluence of the triphenylphosphane ligands over the nitrate ligand. The overall molecular architecture therefore agrees with that of a number of similar 3-L-3,3-L′2-3,1,2-closo-MC2B9H11species in the literature.</jats:p

Small Molecule Inhibitors of Metabolic Enzymes Repurposed as a New Class of Anthelmintics

We thank Qi Wang for her technical assistance related to clustering compounds and identifying representatives for screening. This work was supported by National Institute of Allergy and Infectious Diseases (NIAID) grant AI081803 to M.M. The study was also partly supported by NIAID grant AI056189 to R.V.A.Peer reviewedPostprin

Phylogenetic and environmental context of a Tournaisian tetrapod fauna

The end-Devonian to mid-Mississippian time interval has long been known for its depauperate palaeontological record, especially for tetrapods. This interval encapsulates the time of increasing terrestriality among tetrapods, but only two Tournaisian localities previously produced tetrapod fossils. Here we describe five new Tournaisian tetrapods ($\textit{Perittodus apsconditus}$, $\textit{Koilops herma}$, $\textit{Ossirarus kierani}$, $\textit{Diploradus austiumensis}$ and $\textit{Aytonerpeton microps}$) from two localities in their environmental context. A phylogenetic analysis retrieved three taxa as stem tetrapods, interspersed among Devonian and Carboniferous forms, and two as stem amphibians, suggesting a deep split among crown tetrapods. We also illustrate new tetrapod specimens from these and additional localities in the Scottish Borders region. The new taxa and specimens suggest that tetrapod diversification was well established by the Tournaisian. Sedimentary evidence indicates that the tetrapod fossils are usually associated with sandy siltstones overlying wetland palaeosols. Tetrapods were probably living on vegetated surfaces that were subsequently flooded. We show that atmospheric oxygen levels were stable across the Devonian/Carboniferous boundary, and did not inhibit the evolution of terrestriality. This wealth of tetrapods from Tournaisian localities highlights the potential for discoveries elsewhere.NERC consortium grants NE/J022713/1 (Cambridge), NE/J020729/1 (Leicester), NE/J021067/1 (BGS), NE/J020621/1 (NMS) and NE/J021091/1 (Southampton

A randomised controlled feasibility trial of family and social network intervention for young people who misuse alcohol and drugs : study protocol (Y-SBNT)

Background: A growing body of research has identified family interventions to be effective in treating young people’s substance use problems. However, despite this evidence, take-up of family-based approaches in the UK has been low. Key factors for this appear to include the resource-intensive nature of most family interventions which challenges implementation and delivery in many service settings and the cultural adaptation of approaches developed in the USA to a UK setting. This study aims to demonstrate the feasibility of recruiting young people to a specifically developed family- and wider social network-based intervention by testing an adapted version of adult social behaviour and network therapy (SBNT). Methods: A pragmatic, randomised controlled, open feasibility trial delivered in two services for young people in the UK. Potential participants are aged 12–18 years referred for drug or alcohol problems to either service. The main purpose of this study is to demonstrate the feasibility of recruiting young people to a specifically developed family and social network-based intervention. The feasibility and acceptability of this intervention will be measured by recruitment rates, treatment retention, follow-up rates and qualitative interviews. The feasibility of training staff from existing services to deliver this intervention will be explored. Using this opportunity to compare the effectiveness of the intervention against treatment as usual, Timeline Follow-Back interviews will document the proportion of days on which the main problem substance was used in the preceding 90-day period at each assessment point. The economic component will examine the feasibility of conducting a full incremental cost-effectiveness analysis of the two treatments. The study will also explore and develop models of patient and public involvement which support the involvement of young people in a study of this nature. Discussion: An earlier phase of work adapted social behaviour and network therapy (adult approach) to produce a purpose-designed youth version supported by a therapy manual and associated resources. This was achieved by consultation with young people with experience of services and professionals working in services for young people. This feasibility trial alongside ongoing consultations with young people will offer a meaningful understanding of processes of delivery and implementation. Trial registration: ISRCTN93446265; Date ISRCTN assigned 31/05/2013

A Synthetic Uric Acid Analog Accelerates Cutaneous Wound Healing in Mice

Wound healing is a complex process involving intrinsic dermal and epidermal cells, and infiltrating macrophages and leukocytes. Excessive oxidative stress and associated inflammatory processes can impair wound healing, and antioxidants have been reported to improve wound healing in animal models and human subjects. Uric acid (UA) is an efficient free radical scavenger, but has a very low solubility and poor tissue penetrability. We recently developed novel UA analogs with increased solubility and excellent free radical-scavenging properties and demonstrated their ability to protect neural cells against oxidative damage. Here we show that the uric acid analog (6, 8 dithio-UA, but not equimolar concentrations of UA or 1, 7 dimethyl-UA) modified the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in ways consistent with enhancement of the wound healing functions of all three cell types. We further show that 6, 8 dithio-UA significantly accelerates the wound healing process when applied topically (once daily) to full-thickness wounds in mice. Levels of Cu/Zn superoxide dismutase were increased in wound tissue from mice treated with 6, 8 dithio-UA compared to vehicle-treated mice, suggesting that the UA analog enhances endogenous cellular antioxidant defenses. These results support an adverse role for oxidative stress in wound healing and tissue repair, and provide a rationale for the development of UA analogs in the treatment of wounds and for modulation of angiogenesis in other pathological conditions

Autoregulation in resistance training : addressing the inconsistencies

Autoregulation is a process that is used to manipulate training based primarily on the measurement of an individual's performance or their perceived capability to perform. Despite being established as a training framework since the 1940s, there has been limited systematic research investigating its broad utility. Instead, researchers have focused on disparate practices that can be considered specific examples of the broader autoregulation training framework. A primary limitation of previous research includes inconsistent use of key terminology (e.g., adaptation, readiness, fatigue, and response) and associated ambiguity of how to implement different autoregulation strategies. Crucially, this ambiguity in terminology and failure to provide a holistic overview of autoregulation limits the synthesis of existing research findings and their dissemination to practitioners working in both performance and health contexts. Therefore, the purpose of the current review was threefold: first, we provide a broad overview of various autoregulation strategies and their development in both research and practice whilst highlighting the inconsistencies in definitions and terminology that currently exist. Second, we present an overarching conceptual framework that can be used to generate operational definitions and contextualise autoregulation within broader training theory. Finally, we show how previous definitions of autoregulation fit within the proposed framework and provide specific examples of how common practices may be viewed, highlighting their individual subtleties

Climatic and topographic changes since the Miocene influenced the diversification and biogeography of the tent tortoise (Psammobates tentorius) species complex in Southern Africa

Background: Climatic and topographic changes function as key drivers in shaping genetic structure and cladogenic radiation in many organisms. Southern Africa has an exceptionally diverse tortoise fauna, harbouring one-third of the world’s tortoise genera. The distribution of Psammobates tentorius (Kuhl, 1820) covers two of the 25 biodiversity hotspots in the world, the Succulent Karoo and Cape Floristic Region. The highly diverged P. tentorius represents an excellent model species for exploring biogeographic and radiation patterns of reptiles in Southern Africa. Results: We investigated genetic structure and radiation patterns against temporal and spatial dimensions since the Miocene in the Psammobates tentorius species complex, using multiple types of DNA markers and niche modelling analyses. Cladogenesis in P. tentorius started in the late Miocene (11.63–5.33 Ma) when populations dispersed from north to south to form two geographically isolated groups. The northern group diverged into a clade north of the Orange River (OR), followed by the splitting of the group south of the OR into a western and an interior clade. The latter divergence corresponded to the intensifcation of the cold Benguela current, which caused western aridifcation and rainfall seasonality. In the south, tectonic uplift and subsequent exhumation, together with climatic fuctuations seemed responsible for radiations among the four southern clades since the late Miocene. We found that each clade occurred in a habitat shaped by diferent climatic parameters, and that the niches difered substantially among the clades of the northern group but were similar among clades of the southern group. Conclusion: Climatic shifts, and biome and geographic changes were possibly the three major driving forces shaping cladogenesis and genetic structure in Southern African tortoise species. Our results revealed that the cladogenesis of the P. tentorius species complex was probably shaped by environmental cooling, biome shifts and topographic uplift in Southern Africa since the late Miocene. The Last Glacial Maximum (LGM) may have impacted the distribution of P. tentorius substantially. We found the taxonomic diversify of the P. tentorius species complex to be highest in the Greater Cape Floristic Region. All seven clades discovered warrant conservation attention, particularly Ptt-B–Ptr, Ptt-A and Pv-