Lake enrichment and the status of Windermere charr, Salvelinus alpinus (L.)

All English populations of Arctic charr, Salvelinus alpinus (L.), are found in the Lake District (northwest England). There are at least four races of charr in Windermere, the largest lake in England; the North and South basins of the lake each contain two distinct races that spawn in autumn and spring respectively. The spring spawners in both basins probably represent less than 15% of the total population in the lake.
Changes in the population density of charr in the lake are described briefly and examined in relation to the trophic status of the lake. Other factors that could possibly affect the charr population are reviewed, especially the influence of climate change.     

Liquid Exfoliated Co(OH)2 Nanosheets as Low‐Cost,Yet High‐Performance,Catalysts for the Oxygen Evolution Reaction

Identifying cheap, yet effective, oxygen evolution catalysts is critical to the advancement of water splitting. Using liquid exfoliated Co(OH)₂ nanosheets as a model system, a simple procedure is developed to maximize the activity of any oxygen evolution reaction nanocatalyst. First the nanosheet edges are confirmed as the active areas by analyzing the catalytic activity as a function of nanosheet size. This allows the authors to select the smallest nanosheets (length ≈50 nm) as the best performing catalysts. While the number of active sites per unit electrode area can be increased via the electrode thickness, this is found to be impossible beyond ≈10 µm due to mechanical instabilities. However, adding carbon nanotubes increases both toughness and conductivity significantly. These enhancements mean that composite electrodes consisting of small Co(OH)₂ nanosheets and 10 wt% nanotubes can be made into freestanding films with thickness of up to 120 µm with no apparent electrical limitations. The presence of diffusion limitations results in an optimum electrode thickness of 70 µm, yielding a current density of 50 mA cm^?2 at an overpotential of 235 mV, close to the state of the art in the field. Applying this procedure to a high‐performance catalyst such as NiFeO_x should significantly surpass the state of the art.     

Using a FRET Library with Multiple Probe Pairs To Drive Monte Carlo Simulations of α-Synuclein

We describe a strategy for experimentally-constraining computational simulations of intrinsically disordered proteins (IDPs), using α-synuclein, an IDP with a central role in Parkinson’s disease pathology, as an example. Previously, data from single-molecule Förster Resonance Energy Transfer (FRET) experiments have been effectively utilized to generate experimentally constrained computational models of IDPs. However, the fluorophores required for single-molecule FRET experiments are not amenable to the study of short-range (<30 Å) interactions. Using ensemble FRET measurements allows one to acquire data from probes with multiple distance ranges, which can be used to constrain Monte Carlo simulations in PyRosetta. To appropriately employ ensemble FRET data as constraints, we optimized the shape and weight of constraining potentials to afford ensembles of structures that are consistent with experimental data. We also used this approach to examine the structure of α-synuclein in the presence of the compacting osmolyte trimethylamine-N-oxide. Despite significant compaction imparted by 2 M trimethylamine-N-oxide, the underlying ensemble of α-synuclein remains largely disordered and capable of aggregation, also in agreement with experimental data. These proof-of-concept experiments demonstrate that our modeling protocol enables one to efficiently generate experimentally constrained models of IDPs that incorporate atomic-scale detail, allowing one to study an IDP under a variety of conditions.     

A20 Deficiency in Lung Epithelial Cells Protects against Influenza A Virus Infection

A20 negatively regulates multiple inflammatory signalling pathways. We here addressed the role of A20 in club cells (also known as Clara cells) of the bronchial epithelium in their response to influenza A virus infection. Club cells provide a niche for influenza virus replication, but little is known about the functions of these cells in antiviral immunity. Using airway epithelial cell-specific A20 knockout (A20^AEC-KO) mice, we show that A20 in club cells critically controls innate immune responses upon TNF or double stranded RNA stimulation. Surprisingly, A20^AEC-KO mice are better protected against influenza A virus challenge than their wild type littermates. This phenotype is not due to decreased viral replication. Instead host innate and adaptive immune responses and lung damage are reduced in A20^AEC-KO mice. These attenuated responses correlate with a dampened cytotoxic T cell (CTL) response at later stages during infection, indicating that A20^AEC-KO mice are better equipped to tolerate Influenza A virus infection. Expression of the chemokine CCL2 (also named MCP-1) is particularly suppressed in the lungs of A20^AEC-KO mice during later stages of infection. When A20^AEC-KO mice were treated with recombinant CCL2 the protective effect was abrogated demonstrating the crucial contribution of this chemokine to the protection of A20^AEC-KO mice to Influenza A virus infection. Taken together, we propose a mechanism of action by which A20 expression in club cells controls inflammation and antiviral CTL responses in response to influenza virus infection.     

Experimental Tests of the Function and Flexibility of Song Consistency in a Wild Bird

Measures of bird song that capture aspects of motor performance, such as consistency, have become a major focus in understanding sexual selection on song. Despite accumulating evidence that consistency is related to reproductive success in many species, the relative importance of male–male interactions and female–male interactions is still unclear. We studied the function and flexibility of song consistency and song rate in common yellowthroat warblers (Geothlypis trichas). A previous study of this population found that song consistency—measured as the amount of variability within a bout of songs—was positively correlated with the likelihood of siring extrapair young. In this study, we conducted two experiments aimed at testing (1) the role of song consistency and rate in mediating male–male and male–female interactions and (2) whether song effort is flexibly adjusted to changes in social context. In the first experiment, we simulated a male territorial intrusion with song playbacks that varied in consistency and rate; focal males responded aggressively to playbacks, but their response did not differ with playback consistency or rate. In the second experiment, we presented focal males with a taxidermic female mount and female vocalizations; focal males approached the speaker, but continued to sing and did not perform the aggressive rattle vocalization observed during male encounters. Immediately after the simulated female encounter, focal males increased in song consistency. Taken together, our results are most consistent with the hypothesis that song consistency in common yellowthroats is primarily a female‐directed signal that is actively adjusted in response to rapidly changing social conditions.     

Measuring the Quality of University Lectures: Development and Validation of the Instructional Skills Questionnaire (ISQ)

In higher education, student ratings are often used to evaluate and improve the quality of courses and professors’ instructional skills. Unfortunately, student-rating questionnaires rarely generate specific feedback for professors to improve their instructional skills. The impact of student ratings on professors’ instructional skills has proven to be low. This study concerns the psychometric properties of the Instructional Skills Questionnaire (ISQ), a new theory-based student-rating-of-teaching questionnaire with specific questions concerning lecturing skills. The ISQ is administered after a single lecture. This way, it serves as a formative feedback instrument for university professors during courses to assist them to improve and (re-) evaluate their skills if necessary. The ISQ contains seven dimensions of professors’ instructional skills and three student (self perceived) learning outcomes. In this study, Dutch students in 75 courses rated three 90-minute lectures (T1, T2 and T3) of their respective professors using the ISQ. In total, 14,298 ISQ-forms were used to rate 225 lectures. The teacher level reliabilities of the seven dimensions were found to be good at each measurement occasion. In addition, confirmatory multilevel factor analysis confirmed a seven dimensional factor structure at the teacher level at each measurement occasion. Furthermore, specific teacher level factors significantly predicted students’ (self-assessed) learning outcomes. These results partly supported the proposed theoretical framework on the relationship between the ISQ teaching dimensions and the student learning process, and provided evidence for the construct validity of the instrument. In sum, the ISQ is found to be a reliable and valid instrument, which can be used by professors and faculty development centers to assess and improve university teaching.     

Structure-Bioactivity Relationship for Benzimidazole Thiophene Inhibitors of Polo-Like Kinase 1 (PLK1), a Potential Drug Target in Schistosoma mansoni

Background

Schistosoma flatworm parasites cause schistosomiasis, a chronic and debilitating disease of poverty in developing countries. Praziquantel is employed for treatment and disease control. However, its efficacy spectrum is incomplete (less active or inactive against immature stages of the parasite) and there is a concern of drug resistance. Thus, there is a need to identify new drugs and drug targets.

Methodology/Principal Findings

We show that RNA interference (RNAi) of the Schistosoma mansoni ortholog of human polo-like kinase (huPLK)1 elicits a deleterious phenotypic alteration in post-infective larvae (schistosomula or somules). Phenotypic screening and analysis of schistosomula and adult S. mansoni with small molecule inhibitors of huPLK1 identified a number of potent anti-schistosomals. Among these was a GlaxoSmithKline (GSK) benzimidazole thiophene inhibitor that has completed Phase I clinical trials for treatment of solid tumor malignancies. We then obtained GSKs Published Kinase Inhibitor Sets (PKIS) 1 and 2, and phenotypically screened an expanded series of 38 benzimidazole thiophene PLK1 inhibitors. Computational analysis of controls and PLK1 inhibitor-treated populations of somules demonstrated a distinctive phenotype distribution. Using principal component analysis (PCA), the phenotypes exhibited by these populations were mapped, visualized and analyzed through projection to a low-dimensional space. The phenotype distribution was found to have a distinct shape and topology, which could be elicited using cluster analysis. A structure-activity relationship (SAR) was identified for the benzimidazole thiophenes that held for both somules and adult parasites. The most potent inhibitors produced marked phenotypic alterations at 1–2 μM within 1 h. Among these were compounds previously characterized as potent inhibitors of huPLK1 in cell assays.

Conclusions/Significance

The reverse genetic and chemical SAR data support a continued investigation of SmPLK1 as a possible drug target and/or the prosecution of the benzimidazole thiophene chemotype as a source of novel anti-schistosomals.     

Gonad growth in the sea urchin, Strongylocentrotus purpuratus (Stimpson) (echinodermata: Echinoidea) and the assumptions of gonad index methods

In central Oregon intertidal populations, the echinoid Strongylocentrotus purpuratus (Stimpson) first begins to produce mature gametes at a diameter of 25 mm during the second year of its life. All individuals above 40 mm in diameter have mature gametes during the mid-winter spawning season. Gonad size increases rapidly relative to body size until the animals are ≈45 mm in diameter and have a total dry weight of ≈ 15 g. The ratio of gonad to body size reaches its maximum in animals between 40 mm and 50 mm in diameter; thereafter the ratio drops slightly with increasing size. The curvilinear relation between gonad size and body size is not related to a relative difference in body proportions with size. Internal volume, height, and diameter increase linearly with size. Body proportions did not differ between the two populations studied. Differences between populations in the ratio of gonad to body size extend to all sizes in the populations and the direction but not the amount of the difference is consistent from year to year. These differences between habitats are probably related to food supply. The use of gonad ratio methods to normalize gonad size assumes that, within a given population, animals of different body size have the same ratio of gonad size to body size. This assumption is not correct for four species of sea urchins. Gonad index or ratio methods are useful for comparing animals of the same size through time within a population or from different habitats. Restriction of the size range of animals used and use of samples of sufficient size permit gonad ratios to be used to assess the capacity of different habitats to support gonad production in sea urchins and other animals.