Ecology of common bully (Gobiomorphus cotidianus) in the Tarawera and Rangitaiki rivers: isolation by inland distance or anthropogenic discharge?

Previous research has identified distinct genetic, life-history and reproductive differences between populations of common bully (Gobiomorphus cotidianus) upstream and downstream of a pulp and paper mill outfall on the Tarawera River in the Bay of Plenty, New Zealand. This study investigated the distribution of common bully in the Tarawera River by examining fish collected from upstream (37 km inland) and downstream (20 km inland) locations and comparing them to fish from similar inland locations (40 km and 17 km inland, respectively) in the nearby Rangitaiki River. Reproductive divergence was observed between upstream and downstream sites of both rivers by differing annual trends in gonadosomatic index. Stable carbon and nitrogen isotopes confirmed residency at each sampling site and otolith microchemistry demonstrated different life-history strategies between upstream and downstream populations. Diadromous recruits dominated in both downstream river populations, with a general disappearance of diadromy upstream. A mixture of diadromous and non-diadromous fish were found in the upstream Rangitaiki River, whereas diadromous recruits were absent in the upstream Tarawera River. A reduction in oculoscapular canal structures also coincided with loss of diadromy in fish from both rivers. A behavioural study to determine whether pulp and paper mill effluent may deter fish migration within the Tarawera River demonstrated a strong avoidance of effluent, but only at concentrations (>25%) greater than those that naturally occur in the river (<15%). The results of this study suggest that combinations of influences coupled with inland distance are likely to be responsible for the isolation of common bully subpopulations within the Tarawera River

An investigation of fingerstick blood collection for pointof- care HIV-1 viral load monitoring in South Africa

Background: Viral load (VL) quantification is an important tool in determining newly developed drug resistance or problems with adherence to antiretroviral therapy (ART) in HIV-positive patients. VL monitoring is becoming the standard of care in many resource-limited settings. Testing in resource-limited settings may require sampling by fingerstick because of general shortages of skilled phlebotomists and the expense of venepuncture supplies and problems with their distribution.Objective: To assess the feasibility and ease of collecting 150 μL capillary blood needed for the use of a novel collection device following a classic fingerstick puncture.Methods: Patients were recruited by the study nurse upon arrival for routine ART monitoring at the Themba Lethu Clinic in Johannesburg, South Africa. Each step of the fingerstick and blood collection protocol was observed, and their completion or omission was recorded.Results: One hundred and three patients consented to the study, of whom three were excluded owing to the presence of callouses. From a total of 100 patients who consented and were enrolled, 98% of collection attempts were successful and 86% of participants required only one fingerstick to successfully collect 150 μL capillary blood. Study nurse adherence to the fingerstick protocol revealed omissions in several steps that may lower the success rate of capillary blood collection and reduce the performance of a subsequent VL assay.Conclusion: The findings of this study support the feasibility of collecting 150 μL of capillary blood via fingerstick for point-of-care HIV-1 VL testing in a resource-limited setting

Discovery of lead compounds targeting the bacterial sliding clamp using a fragment-based approach

The bacterial sliding clamp (SC), also known as the DNA polymerase III β subunit, is an emerging antibacterial target that plays a central role in DNA replication, serving as a protein-protein interaction hub with a common binding pocket to recognize linear motifs in the partner proteins. Here, fragment-based screening using X-ray crystallography produced four hits bound in the linear-motif-binding pocket of the Escherichia coli SC. Compounds structurally related to the hits were identified that inhibited the E. coli SC and SC-mediated DNA replication in vitro. A tetrahydrocarbazole derivative emerged as a promising lead whose methyl and ethyl ester prodrug forms showed minimum inhibitory concentrations in the range of 21-43 μg/mL against representative Gram-negative and Gram-positive bacteria species. The work demonstrates the utility of a fragment-based approach for identifying bacterial sliding clamp inhibitors as lead compounds with broad-spectrum antibacterial activity. © 2014 American Chemical Society

Psychological interventions in asthma

Asthma is a multifactorial chronic respiratory disease characterised by recurrent episodes of airway obstruction. The current management of asthma focuses principally on pharmacological treatments, which have a strong evidence base underlying their use. However, in clinical practice, poor symptom control remains a common problem for patients with asthma. Living with asthma has been linked with psychological co-morbidity including anxiety, depression, panic attacks and behavioural factors such as poor adherence and suboptimal self-management. Psychological disorders have a higher-than-expected prevalence in patients with difficult-to-control asthma. As psychological considerations play an important role in the management of people with asthma, it is not surprising that many psychological therapies have been applied in the management of asthma. There are case reports which support their use as an adjunct to pharmacological therapy in selected individuals, and in some clinical trials, benefit is demonstrated, but the evidence is not consistent. When findings are quantitatively synthesised in meta-analyses, no firm conclusions are able to be drawn and no guidelines recommend psychological interventions. These inconsistencies in findings may in part be due to poor study design, the combining of results of studies using different interventions and the diversity of ways patient benefit is assessed. Despite this weak evidence base, the rationale for psychological therapies is plausible, and this therapeutic modality is appealing to both patients and their clinicians as an adjunct to conventional pharmacological treatments. What are urgently required are rigorous evaluations of psychological therapies in asthma, on a par to the quality of pharmaceutical trials. From this evidence base, we can then determine which interventions are beneficial for our patients with asthma management and more specifically which psychological therapy is best suited for each patient

No systemic reactions to influenza vaccination in egg-sensitized tertiary-care pediatric patients

<p>Abstract</p> <p>Background</p> <p>There are numerous, disparate guidelines for influenza vaccination in egg-allergic patients. We aimed to describe the outcome of selectively applied guidelines, based on risk-stratification, to our high risk, egg-allergic, tertiary-care pediatric population.</p> <p>Methods</p> <p>Egg allergy was confirmed with skin testing. The vaccine administered was an adjuvunated 2009 H1N1 influenza A vaccine with < 0.165 mcg/ml ovalbumin. Patients with mild egg allergy were to receive the vaccination in 1 dose, those with severe egg allergy were to receive 2 split doses, and patients with exquisite egg allergy or significant co-morbidities were to be skin tested with the vaccine (prick full strength, intradermal 1:100 of final concentration without adjuvant) and had 5 step desensitization if the testing was positive, or 1-2 step administration if negative. Patients were observed for 60 minutes after the final dose and anaphylaxis treatment was available. We report the frequency of allergic reactions.</p> <p>Results</p> <p>Ninety-nine patients were referred and 79 had positive egg testing. Asthma was present in 67% and 30% had prior anaphylaxis to egg. We vaccinated 77 of 79 patients: 71 without performing vaccine skin testing. Two refused vaccination. No patient had a systemic reaction or required treatment. Two patients experienced positive testing to the adjuvanated intradermal vaccine, but were negative without adjuvant.</p> <p>Conclusions</p> <p>Our results suggest that most egg-allergic tertiary care pediatric patients can be vaccinated with a low ovalbumin content influenza vaccine without prior vaccine testing. Vaccine skin testing, if used at all, can be reserved for special circumstances. The squalene adjuvant may cause an irritant reaction with intradermal testing.</p

Transfer of learning between unimanual and bimanual rhythmic movement coordination: transfer is a function of the task dynamic.

Under certain conditions, learning can transfer from a trained task to an untrained version of that same task. However, it is as yet unclear what those certain conditions are or why learning transfers when it does. Coordinated rhythmic movement is a valuable model system for investigating transfer because we have a model of the underlying task dynamic that includes perceptual coupling between the limbs being coordinated. The model predicts that (1) coordinated rhythmic movements, both bimanual and unimanual, are organised with respect to relative motion information for relative phase in the coupling function, (2) unimanual is less stable than bimanual coordination because the coupling is unidirectional rather than bidirectional, and (3) learning a new coordination is primarily about learning to perceive and use the relevant information which, with equal perceptual improvement due to training, yields equal transfer of learning from bimanual to unimanual coordination and vice versa [but, given prediction (2), the resulting performance is also conditioned by the intrinsic stability of each task]. In the present study, two groups were trained to produce 90° either unimanually or bimanually, respectively, and tested in respect to learning (namely improved performance in the trained 90° coordination task and improved visual discrimination of 90°) and transfer of learning (to the other, untrained 90° coordination task). Both groups improved in the task condition in which they were trained and in their ability to visually discriminate 90°, and this learning transferred to the untrained condition. When scaled by the relative intrinsic stability of each task, transfer levels were found to be equal. The results are discussed in the context of the perception–action approach to learning and performance

The T7-Primer Is a Source of Experimental Bias and Introduces Variability between Microarray Platforms

Eberwine(-like) amplification of mRNA adds distinct 6–10 bp nucleotide stretches to the 5′ end of amplified RNA transcripts. Analysis of over six thousand microarrays reveals that probes containing motifs complementary to these stretches are associated with aberrantly high signals up to a hundred fold the signal observed in unaffected probes. This is not observed when total RNA is used as target source. Different T7 primer sequences are used in different laboratories and platforms and consequently different T7 primer bias is observed in different datasets. This will hamper efforts to compare data sets across platforms

Motor coordination: when two have to act as one

Trying to pass someone walking toward you in a narrow corridor is a familiar example of a two-person motor game that requires coordination. In this study, we investigate coordination in sensorimotor tasks that correspond to classic coordination games with multiple Nash equilibria, such as “choosing sides,” “stag hunt,” “chicken,” and “battle of sexes”. In these tasks, subjects made reaching movements reflecting their continuously evolving “decisions” while they received a continuous payoff in the form of a resistive force counteracting their movements. Successful coordination required two subjects to “choose” the same Nash equilibrium in this force-payoff landscape within a single reach. We found that on the majority of trials coordination was achieved. Compared to the proportion of trials in which miscoordination occurred, successful coordination was characterized by several distinct features: an increased mutual information between the players’ movement endpoints, an increased joint entropy during the movements, and by differences in the timing of the players’ responses. Moreover, we found that the probability of successful coordination depends on the players’ initial distance from the Nash equilibria. Our results suggest that two-person coordination arises naturally in motor interactions and is facilitated by favorable initial positions, stereotypical motor pattern, and differences in response times

Option selection in whole-body rotation movements in gymnastics

Abstract When a gymnast performs a somersault, the linear and angular momentum along with a particular control of inertia during the flight phase constrain the possibilities for action. Given the complexity and dynamic nature of the human moving system, one could argue that there exist a particular amount of stable coordination states when performing somersaults. The goal of this study was to explore the manifold of movement options and coordination states along with their differentiating parameters for a single somersault in gymnastics based on a simple mathematical model reflecting gymnast’s rotation behavior during the flight phase. Biomechanical parameters determining rotation behavior during a somersault were systematically varied with regard to a particular set of biomechanical constraints defining a successful somersault performance. Batch simulations revealed that from 10229760 simulation cycles only 655346 (approximately 6.41%) led to successful somersault performance. A subsequent analysis of the movement option landscape for the optimum angular momentum revealed ten coordination states for a single somersault that could be clearly distinguished based on the simulation parameters. Taken the results together, it becomes apparent that it may be most advisable to perform a single somersault with a larger moment of inertia when achieving the tucked position, a longer duration to achieve the tucked position, a longer duration of staying tucked, and an intermediate moment of inertia during landing. This strategy comprises the largest amount of movement options associated with an upright landing and thus the highest probability of success when performing a single somersault

Stepwise Maturation of Lytic Granules during Differentiation and Activation of Human CD8+ T Lymphocytes

During differentiation, cytotoxic T lymphocytes (CTL) acquire their killing potential through the biogenesis and maturation of lytic granules that are secreted upon target cell recognition. How lytic granule load in lytic molecules evolves during CTL differentiation and which subsets of lytic granules are secreted following activation remains to be investigated. We set up a flow cytometry approach to analyze single lytic granules isolated from primary human CTL according to their size and molecular content. During CTL in vitro differentiation, a relatively homogeneous population of lytic granules appeared through the progressive loading of Granzyme B, Perforin and Granzyme A within LAMP1+ lysosomes. PMA/ionomycin-induced lytic granule exocytosis was preceded by a rapid association of the docking molecule Rab27a to approximately half of the lytic granules. Activated CTL were found to limit exocytosis by sparing lytic granules including some associated to Rab27a. Our study provides a quantification of key steps of lytic granule biogenesis and highlights the potential of flow cytometry to study organelle composition and dynamics