A Cross-Sectional Study of People with Epilepsy and Neurocysticercosis in Tanzania: Clinical Characteristics and Diagnostic Approaches.

Neurocysticercosis (NCC) is a major cause of epilepsy in regions where pigs are free-ranging and hygiene is poor. Pork production is expected to increase in the next decade in sub-Saharan Africa, hence NCC will likely become more prevalent. In this study, people with epilepsy (PWE, n=212) were followed up 28.6 months after diagnosis of epilepsy. CT scans were performed, and serum and cerebrospinal fluid (CSF) of selected PWE were analysed. We compared the demographic data, clinical characteristics, and associated risk factors of PWE with and without NCC. PWE with NCC (n=35) were more likely to be older at first seizure (24.3 vs. 16.3 years, p=0.097), consumed more pork (97.1% vs. 73.6%, p=0.001), and were more often a member of the Iraqw tribe (94.3% vs. 67.8%, p=0.005) than PWE without NCC (n=177). PWE and NCC who were compliant with anti-epileptic medications had a significantly higher reduction of seizures (98.6% vs. 89.2%, p=0.046). Other characteristics such as gender, seizure frequency, compliance, past medical history, close contact with pigs, use of latrines and family history of seizures did not differ significantly between the two groups. The number of NCC lesions and active NCC lesions were significantly associated with a positive antibody result. The electroimmunotransfer blot, developed by the Centers for Disease Control and Prevention, was more sensitive than a commercial western blot, especially in PWE and cerebral calcifications. This is the first study to systematically compare the clinical characteristics of PWE due to NCC or other causes and to explore the utility of two different antibody tests for diagnosis of NCC in sub-Saharan Africa

Associations of sitting accumulation patterns with cardio-metabolic risk biomarkers in Australian adults

Backgroun

A [4Fe-4S]-Fe(CO)(CN)-L-cysteine intermediate is the first organometallic precursor in [FeFe] hydrogenase H-cluster bioassembly.

Biosynthesis of the [FeFe] hydrogenase active site (the 'H-cluster') requires the interplay of multiple proteins and small molecules. Among them, the radical S-adenosylmethionine enzyme HydG, a tyrosine lyase, has been proposed to generate a complex that contains an Fe(CO)2(CN) moiety that is eventually incorporated into the H-cluster. Here we describe the characterization of an intermediate in the HydG reaction: a [4Fe-4S][(Cys)Fe(CO)(CN)] species, 'Complex A', in which a CO, a CN- and a cysteine (Cys) molecule bind to the unique 'dangler' Fe site of the auxiliary [5Fe-4S] cluster of HydG. The identification of this intermediate-the first organometallic precursor to the H-cluster-validates the previously hypothesized HydG reaction cycle and provides a basis for elucidating the biosynthetic origin of other moieties of the H-cluster

Quantum physics meets biology

Quantum physics and biology have long been regarded as unrelated disciplines, describing nature at the inanimate microlevel on the one hand and living species on the other hand. Over the last decades the life sciences have succeeded in providing ever more and refined explanations of macroscopic phenomena that were based on an improved understanding of molecular structures and mechanisms. Simultaneously, quantum physics, originally rooted in a world view of quantum coherences, entanglement and other non-classical effects, has been heading towards systems of increasing complexity. The present perspective article shall serve as a pedestrian guide to the growing interconnections between the two fields. We recapitulate the generic and sometimes unintuitive characteristics of quantum physics and point to a number of applications in the life sciences. We discuss our criteria for a future quantum biology, its current status, recent experimental progress and also the restrictions that nature imposes on bold extrapolations of quantum theory to macroscopic phenomena.Comment: 26 pages, 4 figures, Perspective article for the HFSP Journa

Retrospective analysis of Schlafen11 (SLFN11) to predict the outcomes to therapies affecting the DNA damage response

BACKGROUND: The absence of the putative DNA/RNA helicase Schlafen11 (SLFN11) is thought to cause resistance to DNAdamaging agents (DDAs) and PARP inhibitors. METHODS: We developed and validated a clinically applicable SLFN11 immunohistochemistry assay and retrospectively correlated SLFN11 tumour levels to patient outcome to the standard of care therapies and olaparib maintenance. RESULTS: High SLFN11 associated with improved prognosis to the first-line treatment with DDAs platinum-plus-etoposide in SCLC patients, but was not strongly linked to paclitaxel–platinum response in ovarian cancer patients. Multivariate analysis of patients with relapsed platinum-sensitive ovarian cancer from the randomised, placebo-controlled Phase II olaparib maintenance Study19 showed SLFN11 tumour levels associated with sensitivity to olaparib. Study19 patients with high SLFN11 had a lower progression-free survival (PFS) hazard ratio compared to patients with low SLFN11, although both groups had the benefit of olaparib over placebo. Whilst caveated by small sample size, this trend was maintained for PFS, but not overall survival, when adjusting for BRCA status across the olaparib and placebo treatment groups, a key driver of PARP inhibitor sensitivity. CONCLUSION: We provide clinical evidence supporting the role of SLFN11 as a DDA therapy selection biomarker in SCLC and highlight the need for further clinical investigation into SLFN11 as a PARP inhibitor predictive biomarker

Similar dispersal patterns between two closely related birds with contrasting migration strategies

Studying dispersal is crucial to understand metapopulation and sink-source dynamics and invasion processes. The capability to disperse is especially important for species living in fragmented habitats like wetlands. We investigated the distribution of natal and breeding dispersal distances and philopatry in Spanish populations of two closely related reedbed-nesting birds, the Moustached Warbler Acrocephalus melanopogon and the Eurasian Reed Warbler Acrocephalus scirpaceus. These warblers are morphologically very similar, but differ in migration strategy and, in our study area, in population size. Our aims were to find the best model for dispersal distances and to assess the occurrence of intra- or interspecific differences in dispersal patterns. We used ringing data from the Spanish marking scheme and selected recaptures to avoid including migrating individuals. In both species, most individuals were philopatric but dispersing birds were able to cross large distances (up to more than 100 km), suggesting the capability to compensate for habitat fragmentation. We found the heavy-tailed Cauchy distribution to be the best conceptual description for our data, in all cases but natal dispersal of Moustached Warblers. Among Eurasian Reed Warblers, natal philopatry was lower than breeding philopatry. We found no significant interspecific differences. This does not confirm the hypothesis of higher dispersal ability in long distance migrants (like Eurasian Reed Warblers) than in resident/short distance migrant bird species (like Moustached Warblers). The similarity in dispersal patterns among the two warblers may be explained by their close phylogenetic relatedness, similar constraints imposed on both species by a patchy habitat or similar evolutionary pressures.We are grateful to the many ringers who collected the data during years of fieldwork in Spain. Francesco Ceresa is supported by an "Atraent talent'' grant from the University of Valencia.Ceresa, F.; Belda, E.; Monrós González, JS. (2016). Similar dispersal patterns between two closely related birds with contrasting migration strategies. Population Ecology. 58(3):421-427. doi:10.1007/s10144-016-0547-0S421427583Banco de datos de anillamiento del remite ICONA – Ministerio de Medio Ambiente (2015) Datos de anillamiento y recuperaciones en España. Ministerio de Agricultura, Alimentación y Medio Ambiente, SEO/BirdLife, ICO, EBD-CSIC y GOB. Madrid (in Spanish)Begon M, Townsend CR, Harper JL (2006) Ecology: from individual to ecosystems, 4th edn. 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Comprehensive phenotypic analysis of the Dp1Tyb mouse strain reveals a broad range of down syndrome-related phenotypes

Down syndrome (DS), trisomy 21, results in many complex phenotypes including cognitive deficits, heart defects and craniofacial alterations. Phenotypes arise from an extra copy of human chromosome 21 (Hsa21) genes. However, these dosage-sensitive causative genes remain unknown. Animal models enable identification of genes and pathological mechanisms. The Dp1Tyb mouse model of DS has an extra copy of 63% of Hsa21-orthologous mouse genes. In order to establish if this model recapitulates DS phenotypes, we comprehensively phenotyped Dp1Tyb mice using 28 tests of different physiological systems and found that 468 out of 1800 parameters were significantly altered. We show that Dp1Tyb mice have wide-ranging DS-like phenotypes including aberrant erythropoiesis and megakaryopoiesis, reduced bone density, craniofacial changes, altered cardiac function, a pre-diabetic state and deficits in memory, locomotion, hearing and sleep. Thus, Dp1Tyb mice are an excellent model for investigating complex DS phenotype-genotype relationships for this common disorder

Quantification of the overall contribution of gene-environment interaction for obesity-related traits

The growing sample size of genome-wide association studies has facilitated the discovery of gene-environment interactions (GxE). Here we propose a maximum likelihood method to estimate the contribution of GxE to continuous traits taking into account all interacting environmental variables, without the need to measure any. Extensive simulations demonstrate that our method provides unbiased interaction estimates and excellent coverage. We also offer strategies to distinguish specific GxE from general scale effects. Applying our method to 32 traits in the UK Biobank reveals that while the genetic risk score (GRS) of 376 variants explains 5.2% of body mass index (BMI) variance, GRSxE explains an additional 1.9%. Nevertheless, this interaction holds for any variable with identical correlation to BMI as the GRS, hence may not be GRS-specific. Still, we observe that the global contribution of specific GRSxE to complex traits is substantial for nine obesity-related measures (including leg impedance and trunk fat-free mass).This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.published version, accepted version, submitted versio

Causes and importance of new particle formation in the present-day and pre-industrial atmospheres

New particle formation has been estimated to produce around half of cloud-forming particles in the present-day atmosphere, via gas-to-particle conversion. Here we assess the importance of new particle formation (NPF) for both the present-day and the pre-industrial atmospheres. We use a global aerosol model with parametrisations of NPF from previously published CLOUD chamber experiments involving sulphuric acid, ammonia, organic molecules and ions. We find that NPF produces around 67% of cloud condensation nuclei at 0.2% supersaturation (CCN0.2%) at the level of low clouds in the pre-industrial atmosphere (estimated uncertainty range 45-84%) and 54% in the present day (estimated uncertainty range 38-66%). Concerning causes, we find that the importance of biogenic volatile organic compounds (BVOCs) in NPF and CCN formation is greater than previously thought. Removing BVOCs and hence all secondary organic aerosol from our model reduces low-cloud-level CCN concentrations at 0.2% supersaturation by 26% in the present-day atmosphere and 41% in the pre-industrial. Around three-quarters of this reduction is due to the tiny fraction of the oxidation products of BVOCs that have sufficiently low volatility to be involved in NPF and early growth. Furthermore, we estimate that 40% of pre-industrial CCN0.2% are formed via ion-induced NPF, compared with 27% in the present-day, although we caution that the ion-induced fraction of NPF involving BVOCs is poorly measured at present. Our model suggests that the effect of changes in cosmic ray intensity on CCN is small and unlikely to be comparable to the effect of large variations in natural primary aerosol emissions