Facilitation of non-indigenous ascidian by marine eco-engineering interventions at an urban site

Marine artificial structures often support lower native species diversity and more non-indigenous species (NIS), but adding complex habitat and using bioreceptive materials have the potential to mitigate these impacts. Here, the interacting effects of structural complexity (flat, complex with pits) and concrete mixture (standard, or with oyster shell or vermiculite aggregate) on recruitment were assessed at two intertidal levels at an urban site. Complex tiles had less green algal cover, oyster shell mixtures had less brown (Ralfsia sp.) algal cover. At a low tidal elevation, the non-indigenous ascidian Styela plicata dominated complex tiles. Additionally, mixtures with oyster shell supported higher total cover of sessile species, and a higher cover of S. plicata. There were no effects of complexity or mixture on biofilm communities and native and NIS richness. Overall, these results suggest that habitat complexity and some bioreceptive materials may facilitate colonisation by a dominant invertebrate invader on artificial structures

Modularity of gene-regulatory networks revealed in sea-star development

Evidence that conserved developmental gene-regulatory networks can change as a unit during deutersostome evolution emerges from a study published in BMC Biology. This shows that genes consistently expressed in anterior brain patterning in hemichordates and chordates are expressed in a similar spatial pattern in another deuterostome, an asteroid echinoderm (sea star), but in a completely different developmental context (the animal-vegetal axis). This observation has implications for hypotheses on the type of development present in the deuterostome common ancestor

Linking Hydrogen (δ2H) Isotopes in Feathers and Precipitation: Sources of Variance and Consequences for Assignment to Isoscapes

Background: Tracking small migrant organisms worldwide has been hampered by technological and recovery limitations and sampling bias inherent in exogenous markers. Naturally occurring stable isotopes of H (d 2 H) in feathers provide an alternative intrinsic marker of animal origin due to the predictable spatial linkage to underlying hydrologically driven flow of H isotopes into foodwebs. This approach can assess the likelihood that a migrant animal originated from a given location(s) within a continent but requires a robust algorithm linking H isotopes in tissues of interest to an appropriate hydrological isotopic spatio-temporal pattern, such as weighted-annual rainfall. However, a number of factors contribute to or alter expected isotopic patterns in animals. We present results of an extensive investigation into taxonomic and environmental factors influencing feather d 2 H patterns across North America. Principal Findings: Stable isotope data were measured from 544 feathers from 40 species and 140 known locations. For d 2 H, the most parsimonious model explaining 83 % of the isotopic variance was found with amount-weighted growingseason precipitation d 2 H, foraging substrate and migratory strategy. Conclusions/Significance: This extensive H isotopic analysis of known-origin feathers of songbirds in North America and elsewhere reconfirmed the strong coupling between tissue d 2 H and global hydrologic d 2 H patterns, and accounting for variance associated with foraging substrate and migratory strategy, can be used in conservation and research for th

A comparison of responses to raised extracellular potassium and endothelium-derived hyperpolarizing factor (EDHF) in rat pressurised mesenteric arteries

The present study examined the hypothesis that potassium ions act as an endothelium-derived hyperpolarizing factor (EDHF) released in response to ACh in small mesenteric arteries displaying myogenic tone. Small mesenteric arteries isolated from rats were set up in a pressure myograph at either 60 or 90 mmHg. After developing myogenic tone, responses to raising extracellular potassium were compared to those obtained with ACh (in the presence of nitric oxide synthase and cyclo- oxygenase inhibitors). The effects of barium and ouabain, or capsaicin, on responses to raised extracellular potassium or ACh were also determined. The effects of raised extracellular potassium levels and ACh on membrane potential, were measured using sharp microelectrodes in pressurised arteries. Rat small mesenteric arteries developed myogenic tone when pressurised. On the background of vascular tone set by a physiological stimulus (i.e pressure), ACh fully dilated the small arteries in a concentration-dependent manner. This response was relatively insensitive to the combination of barium and ouabain, and insensitive to capsaicin. Raising extracellular potassium produced a more inconsistent and modest vasodilator response in pressurised small mesenteric arteries. Responses to raising extracellular potassium were sensitive to capsaicin, and the combination of barium and ouabain. ACh caused a substantial hyperpolarisation in pressurized arteries, while raising extracellular potassium did not. These data indicate that K+ is not the EDHF released in response to ACh in myogenically active rat mesenteric small arteries. Since the hyperpolarization produced by ACh was sensitive to carbenoxolone, gap junctions are the likely mediator of EDH responses under physiological conditions

Delayed self-recognition in children with autism spectrum disorder.

This study aimed to investigate temporally extended self-awareness (awareness of one’s place in and continued existence through time) in autism spectrum disorder (ASD), using the delayed self-recognition (DSR) paradigm (Povinelli et al., Child Development 67:1540–1554, 1996). Relative to age and verbal ability matched comparison children, children with ASD showed unattenuated performance on the DSR task, despite showing significant impairments in theory-of-mind task performance, and a reduced propensity to use personal pronouns to refer to themselves. The results may indicate intact temporally extended self-awareness in ASD. However, it may be that the DSR task is not an unambiguous measure of temporally extended self-awareness and it can be passed through strategies which do not require the possession of a temporally extended self-concept

Exploring deliberate practice in medicine: how do physicians learn in the workplace?

Medical professionals need to keep on learning as part of their everyday work to deliver high-quality health care. Although the importance of physicians’ learning is widely recognized, few studies have investigated how they learn in the workplace. Based on insights from deliberate practice research, this study examined the activities physicians engage in during their work that might further their professional development. As deliberate practice requires a focused effort to improve performance, the study also examined the goals underlying this behaviour. Semi-structured interviews were conducted with 50 internal medicine physicians: 19 residents, 18 internists working at a university hospital, and 13 working at a non-university hospital. The results showed that learning in medical practice was very much embedded in clinical work. Most relevant learning activities were directly related to patient care rather than motivated by competence improvement goals. Advice and feedback were sought when necessary to provide this care. Performance standards were tied to patients’ conditions. The patients encountered and the discussions with colleagues about patients were valued most for professional development, while teaching and updating activities were also valued in this respect. In conclusion, physicians’ learning is largely guided by practical experience rather than deliberately sought. When professionals interact in diagnosing and treating patients to achieve high-quality care, their experiences contribute to expertise development. However, much could be gained from managing learning opportunities more explicitly. We offer suggestions for increasing the focus on learning in medical practice and further research

Coevolved mutations reveal distinct architectures for two core proteins in the bacterial flagellar motor

Switching of bacterial flagellar rotation is caused by large domain movements of the FliG protein triggered by binding of the signal protein CheY to FliM. FliG and FliM form adjacent multi-subunit arrays within the basal body C-ring. The movements alter the interaction of the FliG C-terminal (FliGC) "torque" helix with the stator complexes. Atomic models based on the Salmonella entrovar C-ring electron microscopy reconstruction have implications for switching, but lack consensus on the relative locations of the FliG armadillo (ARM) domains (amino-terminal (FliGN), middle (FliGM) and FliGC) as well as changes during chemotaxis. The generality of the Salmonella model is challenged by the variation in motor morphology and response between species. We studied coevolved residue mutations to determine the unifying elements of switch architecture. Residue interactions, measured by their coevolution, were formalized as a network, guided by structural data. Our measurements reveal a common design with dedicated switch and motor modules. The FliM middle domain (FliMM) has extensive connectivity most simply explained by conserved intra and inter-subunit contacts. In contrast, FliG has patchy, complex architecture. Conserved structural motifs form interacting nodes in the coevolution network that wire FliMM to the FliGC C-terminal, four-helix motor module (C3-6). FliG C3-6 coevolution is organized around the torque helix, differently from other ARM domains. The nodes form separated, surface-proximal patches that are targeted by deleterious mutations as in other allosteric systems. The dominant node is formed by the EHPQ motif at the FliMMFliGM contact interface and adjacent helix residues at a central location within FliGM. The node interacts with nodes in the N-terminal FliGc α-helix triad (ARM-C) and FliGN. ARM-C, separated from C3-6 by the MFVF motif, has poor intra-network connectivity consistent with its variable orientation revealed by structural data. ARM-C could be the convertor element that provides mechanistic and species diversity.JK was supported by Medical Research Council grant U117581331. SK was supported by seed funds from Lahore University of Managment Sciences (LUMS) and the Molecular Biology Consortium

Inhibiting mycobacterial tryptophan synthase by targeting the inter-subunit interface

Drug discovery efforts against the pathogen Mycobacterium tuberculosis (Mtb) have been advanced through phenotypic screens of extensive compound libraries. Such a screen revealed sulfolane 1 and indoline-5-sulfonamides 2 and 3 as potent inhibitors of mycobacterial growth. Optimization in the sulfolane series led to compound 4, which has proven activity in an in vivo murine model of Mtb infection. Here we identify the target and mode of inhibition of these compounds based on whole genome sequencing of spontaneous resistant mutants, which identified mutations locating to the essential α- and β-subunits of tryptophan synthase. Over-expression studies confirmed tryptophan synthase as the biological target. Biochemical techniques probed the mechanism of inhibition, revealing the mutant enzyme complex incurs a fitness cost but does not prevent inhibitor binding. Mapping of the resistance conferring mutations onto a low-resolution crystal structure of Mtb tryptophan synthase showed they locate to the interface between the α- and β-subunits. The discovery of anti-tubercular agents inhibiting tryptophan synthase highlights the therapeutic potential of this enzyme and draws attention to the prospect of other amino acid biosynthetic pathways as future Mtb drug targets

A Third Measure-Metastable State in the Dynamics of Spontaneous Shape Change in Healthy Human's White Cells

Human polymorphonuclear leucocytes, PMN, are highly motile cells with average 12-15 µm diameters and prominent, loboid nuclei. They are produced in the bone marrow, are essential for host defense, and are the most populous of white blood cell types. PMN also participate in acute and chronic inflammatory processes, in the regulation of the immune response, in angiogenesis, and interact with tumors. To accommodate these varied functions, their behavior is adaptive, but still definable in terms of a set of behavioral states. PMN morphodynamics have generally involved a non-equilibrium stationary, spheroid Idling state that transitions to an activated, ellipsoid translocating state in response to chemical signals. These two behavioral shape-states, spheroid and ellipsoid, are generally recognized as making up the vocabulary of a healthy PMN. A third, “random” state has occasionally been reported as associated with disease states. I have observed this third, Treadmilling state, in PMN from healthy subjects, the cells demonstrating metastable dynamical behaviors known to anticipate phase transitions in mathematical, physical, and biological systems. For this study, human PMN were microscopically imaged and analyzed as single living cells. I used a microscope with a novel high aperture, cardioid annular condenser with better than 100 nanometer resolution of simultaneous, mixed dark field and intrinsic fluorescent images to record shape changes in 189 living PMNs. Relative radial roundness, R(t), served as a computable order parameter. Comparison of R(t) series of 10 cells in the Idling and 10 in the Treadmilling state reveals the robustness of the “random” appearing Treadmilling state, and the emergence of behaviors observed in the neighborhood of global state transitions, including increased correlation length and variance (divergence), sudden jumps, mixed phases, bimodality, power spectral scaling and temporal slowing. Wavelet transformation of an R(t) series of an Idling to Treadmilling state change, demonstrated behaviors concomitant with the observed transition

Using a New Odour-Baited Device to Explore Options for Luring and Killing Outdoor-Biting Malaria Vectors: A Report on Design and Field Evaluation of the Mosquito Landing Box.

Mosquitoes that bite people outdoors can sustain malaria transmission even where effective indoor interventions such as bednets or indoor residual spraying are already widely used. Outdoor tools may therefore complement current indoor measures and improve control. We developed and evaluated a prototype mosquito control device, the 'Mosquito Landing Box' (MLB), which is baited with human odours and treated with mosquitocidal agents. The findings are used to explore technical options and challenges relevant to luring and killing outdoor-biting malaria vectors in endemic settings. Field experiments were conducted in Tanzania to assess if wild host-seeking mosquitoes 1) visited the MLBs, 2) stayed long or left shortly after arrival at the device, 3) visited the devices at times when humans were also outdoors, and 4) could be killed by contaminants applied on the devices. Odours suctioned from volunteer-occupied tents were also evaluated as a potential low-cost bait, by comparing baited and unbaited MLBs. There were significantly more Anopheles arabiensis, An. funestus, Culex and Mansonia mosquitoes visiting baited MLB than unbaited controls (P<=0.028). Increasing sampling frequency from every 120 min to 60 and 30 min led to an increase in vector catches of up to 3.6 fold (P<=0.002), indicating that many mosquitoes visited the device but left shortly afterwards. Outdoor host-seeking activity of malaria vectors peaked between 7:30 and 10:30pm, and between 4:30 and 6:00am, matching durations when locals were also outdoors. Maximum mortality of mosquitoes visiting MLBs sprayed or painted with formulations of candidate mosquitocidal agent (pirimiphos-methyl) was 51%. Odours from volunteer occupied tents attracted significantly more mosquitoes to MLBs than controls (P<0.001). While odour-baited devices such as the MLBs clearly have potential against outdoor-biting mosquitoes in communities where LLINs are used, candidate contaminants must be those that are effective at ultra-low doses even after short contact periods, since important vector species such as An. arabiensis make only brief visits to such devices. Natural human odours suctioned from occupied dwellings could constitute affordable sources of attractants to supplement odour baits for the devices. The killing agents used should be environmentally safe, long lasting, and have different modes of action (other than pyrethroids as used on LLINs), to curb the risk of physiological insecticide resistance