Evolution of reproductive development in the volvocine algae

The evolution of multicellularity, the separation of germline cells from sterile somatic cells, and the generation of a male–female dichotomy are certainly among the greatest innovations of eukaryotes. Remarkably, phylogenetic analysis suggests that the shift from simple to complex, differentiated multicellularity was not a unique progression in the evolution of life, but in fact a quite frequent event. The spheroidal green alga Volvox and its close relatives, the volvocine algae, span the full range of organizational complexity, from unicellular and colonial genera to multicellular genera with a full germ–soma division of labor and male–female dichotomy; thus, these algae are ideal model organisms for addressing fundamental issues related to the transition to multicellularity and for discovering universal rules that characterize this transition. Of all living species, Volvox carteri represents the simplest version of an immortal germline producing specialized somatic cells. This cellular specialization involved the emergence of mortality and the production of the first dead ancestors in the evolution of this lineage. Volvocine algae therefore exemplify the evolution of cellular cooperation from cellular autonomy. They also serve as a prime example of the evolution of complex traits by a few successive, small steps. Thus, we learn from volvocine algae that the evolutionary transition to complex, multicellular life is probably much easier to achieve than is commonly believed

Reconstruction and flux-balance analysis of the Plasmodium falciparum metabolic network

In the paper we present a metabolic reconstruction and flux-balance analysis (FBA) of Plasmodium falciparum, the primary agent of malaria. The compartmentalized metabolic network of the parasite accounts for 1001 reactions and 616 metabolites. Enzyme–gene associations were established for 366 genes and 75% of all enzymatic reactions.The model was able to reproduce phenotypes of experimental gene knockout and drug inhibition assays with up to 90% accuracy. The model also can be used to efficiently integrate mRNA-expression data to improve the accuracy of metabolic predictions.Using FBA of the reconstructed metabolic network, we identified 40 enzymatic drug targets (i.e. in silico essential genes) with no or very low sequence identity to human proteins.We experimentally tested one of the identified drug targets, nicotinate mononucleotide adenylyltransferase, using a recently discovered small-molecule inhibitor

A Season of American Football Is Not Associated with Changes in Plasma Tau

American football athletes are routinely exposed to sub-concussive impacts over the course of the season. This study sought to examine the effect of a season of American football on plasma tau, a potential marker of axonal damage. Nineteen National Collegiate Athletic Association (NCAA) football athletes underwent serial blood sampling over the course of the 2014–2015 season at those times in which the number and magnitude of head impacts likely changed. Non-contact sport controls (NCAA men's swim athletes; n = 19) provided a single plasma sample for comparison. No significant differences were observed between control swim athletes and football athletes following a period of non-contact (p = 0.569) or a period of contact (p = 0.076). Football athletes categorized as starters (n = 11) had higher tau concentrations than non-starters (n = 8) following a period of non-contact (p = 0.039) and contact (p = 0.036), but not higher than swimmers (p = 1.000 and p = 1.000, respectively). No difference was noted over the course of the season in football athletes, irrespective of starter status. Despite routine head impacts common to the sport of American football, no changes were observed over the course of the season in football athletes, irrespective of starter status. Further, no difference was observed between football athletes and non-contact control swim athletes following a period of non-contact or contact. These data suggest that plasma tau is not sensitive enough to detect damage associated with repetitive sub-concussive impacts sustained by collegiate–level football athletes

Effect of Docosahexaenoic Acid on a Biomarker of Head Trauma in American Football

PURPOSE: American football athletes are exposed to subconcussive impacts over the course of the season resulting in elevations in serum neurofilament light (NFL), a biomarker of axonal injury. Docosahexaenoic acid (DHA) has been reported to reduce axonal trauma associated with traumatic brain injury in rodent models. However, the optimal dose in American football athletes is unknown. This study examined the effect of differing doses of DHA on serum NFL over the course of a season of American football. METHODS: In a randomized, double-blind, placebo-controlled, parallel design, 81 National Collegiate Athletic Association Division I American football athletes were assigned to ingest either 2, 4, 6 g·d−1 of DHA or placebo. Blood was sampled at specific times over the course of 189 d, coincident with changes in intensity, hours of contact, and likely changes in head impacts. Standardized magnitude-based inference was used to define outcomes. RESULTS: DHA supplementation increased plasma DHA in a dose-dependent manner (2 g·d⁻¹: mean difference from baseline; ±90% CL; 2 g·d⁻¹: 1.3; ±0.6; 4 g·d⁻¹: 1.6; ±0.7%; 6 g·d⁻¹: 1.6; ±0.7%; 6 g·d⁻¹) versus nonstarters (1398 ± 581 pg·mL⁻¹; P = 0.024). Irrespective of dose, supplemental DHA likely attenuated serum NFL coincident with increases in serum NFL by likely small and moderate magnitude (effect size = 0.4–0.7). CONCLUSIONS: Findings from this study, the first large-scale study examining potential prophylactic use of DHA in American football athletes, include identification of optimal dose of DHA, suggesting a neuroprotective effect of DHA supplementation

Magnetic Phase transitions in Plasmas and Transport Barriers

A model of magnetic phase transitions in plasmas is presented: plasma blobs with pressure excess or defect are dia- or para-magnets and move radially under the influence of the background plasma magnetisation. It is found that magnetic phase separation could be the underlying mechanism of L to H transitions and drive transport barrier formation. Magnetic phase separation and associated pedestal build up, as described here, can be explained by the well known interchange mechanism, now reinterpreted as a magnetisation interchange which remains relevant even when stable or saturated. A testable necessary criterion for the L to H transition is presented.Comment: 3 figures, 9 pages, equations created with MathType To be published in Nuclear Fusion, accepted August 201

The electrophotonic silicon biosensor

The emergence of personalized and stratified medicine requires label-free and low-cost diagnostic technology capable of monitoring multiple disease biomarkers in parallel. Silicon photonic biosensors combine high sensitivity analysis with scalable, low-cost manufacturing technology but they tend to measure only a single biomarker and provide no information about their (bio)chemical activity. Here, we introduce an electrochemical silicon photonic sensor capable of highly sensitive and multiparameter profiling of biomolecules. Our electro-photonic technology consists of microring resonators optimally n-doped to support high Q resonances alongside electrochemical processes in situ. The inclusion of electrochemical processes enables site selective immobilization of different biomolecules, here single stranded DNA, onto individual microrings within a sensor array. The combination of photonic and electrochemical characterization of molecules bound to the sensor surface also provides direct quantification of binding density and unique insight into chemical reactivity that is unavailable with photonic detection alone. By exploiting both the photonic and the electrical properties of silicon, the sensor opens new modalities for sensing on the micro-scale

An inter-laboratory comparison of urinary 3-hydroxypropylmercapturic acid measurement demonstrates good reproducibility between laboratories

<p>Abstract</p> <p>Background</p> <p>Biomarkers have been used extensively in clinical studies to assess toxicant exposure in smokers and non-smokers and have recently been used in the evaluation of novel tobacco products. The urinary metabolite 3-HPMA, a metabolite of the major tobacco smoke toxicity contributor acrolein, is one example of a biomarker used to measure exposure to tobacco smoke. A number of laboratories have developed liquid chromatography with tandem mass spectrometry (LC-MS/MS) based methods to measure urinary 3-HPMA; however, it is unclear to what extent the data obtained by these different laboratories are comparable.</p> <p>Findings</p> <p>This report describes an inter-laboratory comparison carried out to evaluate the comparability of 3-HPMA measurement between four laboratories. A common set of spiked and authentic smoker and non-smoker urine samples were used. Each laboratory used their in-house LC-MS/MS method and a common internal standard. A comparison of the repeatability ('r'), reproducibility ('R'), and coefficient of variation for 3-HPMA demonstrated that within-laboratory variation was consistently lower than between-laboratory variation. The average inter-laboratory coefficient of variation was 7% for fortified urine samples and 16.2% for authentic urine samples. Together, this represents an inter-laboratory variation of 12.2%.</p> <p>Conclusion</p> <p>The results from this first inter-laboratory comparison for the measurement of 3-HPMA in urine demonstrate a reasonably good consensus between laboratories. However, some consistent measurement biases were still observed between laboratories, suggesting that additional work may be required to further reduce the inter-laboratory coefficient of variation.</p

Treatment adherence with the easypod™ growth hormone electronic auto-injector and patient acceptance: survey results from 824 children and their parents

<p>Abstract</p> <p>Background</p> <p>Accurately monitoring adherence to treatment with recombinant human growth hormone (r-hGH) enables appropriate intervention in cases of poor adherence. The electronic r-hGH auto-injector, easypod™, automatically records the patient's adherence to treatment. This study evaluated adherence to treatment of children who started using the auto-injector and assessed opinions about the device.</p> <p>Methods</p> <p>A multicentre, multinational, observational 3-month survey in which children received r-hGH as part of their normal care. Physicians reviewed the recorded dose history and children (with or without parental assistance) completed a questionnaire-based survey. Children missing ≤2 injections per month (92% of injections given) were considered adherent to treatment. Adherence was compared between GH treatment-naïve and treatment-experienced children.</p> <p>Results</p> <p>Of 834 recruited participants, 824 were evaluated. The median (range) age was 11 (1-18) years. From the recorded dose history, 87.5% of children were adherent to treatment over the 3-month period. Recorded adherence was higher in treatment-naïve (89.7%, n = 445/496) than in treatment-experienced children (81.7%, n = 152/186) [Fisher's exact test FI(X) = 7.577; <it>p </it>= 0.0062]. According to self-reported data, 90.2% (607/673) of children were adherent over 3 months; 51.5% (421/817) missed ≥1 injection over this period (mainly due to forgetfulness). Concordance between reported and recorded adherence was 84.3%, with a trend towards self-reported adherence being higher than recorded adherence. Most children liked the auto-injector: over 80% gave the top two responses from five options for ease of use (720/779), speed (684/805) and comfort (716/804). Although 38.5% (300/780) of children reported pain on injection, over half of children (210/363) considered the pain to be less or much less than expected. Given the choice, 91.8% (732/797) of children/parents would continue using the device.</p> <p>Conclusions</p> <p>easypod™ provides an accurate method of monitoring adherence to treatment with r-hGH. In children who received treatment with r-hGH using easypod™, short-term adherence is good, and significantly higher in treatment-naïve children compared with experienced children. Children/parents rate the device highly. The high level of acceptability of the device is reflected by a desire to continue using it by over 90% of the children in the survey.</p