The Unusual Substrate Specificity of a Virulence Associated Serine Hydrolase from the Highly Toxic Bacterium, \u3cem\u3eFrancisella tularensis\u3c/em\u3e

Francisella tularensis is the causative agent of the highly, infectious disease, tularemia. Amongst the genes identified as essential to the virulence of F. tularensis was the proposed serine hydrolase FTT0941c. Herein, we purified FTT0941c to homogeneity and then characterized the folded stability, enzymatic activity, and substrate specificity of FTT0941c. Based on phylogenetic analysis, FTT0941c was classified within a divergent Francisella subbranch of the bacterial hormone sensitive lipase (HSL) superfamily, but with the conserved sequence motifs of a bacterial serine hydrolase. FTT0941c showed broad hydrolase activity against diverse libraries of ester substrates, including significant hydrolytic activity across alkyl ester substrates from 2 to 8 carbons in length. Among a diverse library of fluorogenic substrates, FTT0941c preferred α-cyclohexyl ester substrates, matching with the substrate specificity of structural homologues and the broad open architecture of its modeled binding pocket. By substitutional analysis, FTT0941c was confirmed to have a classic catalytic triad of Ser115, His278, and Asp248 and to remain thermally stable even after substitution. Its overall substrate specificity profile, divergent phylogenetic homology, and preliminary pathway analysis suggested potential biological functions for FTT0941c in diverse metabolic degradation pathways in F. tularensis

Despite a variety of ballot measures and some expensive races, the midterms were relatively quiet for judicial elections

While most commentators have been focused on the outcome of key Senate races in this year’s midterm elections, it is important to remember that many states were also electing judges for high courts as well this week. Chris W. Bonneau and Jeremy R. Johnson give an overview of the results including a million dollar race in North Carolina, ballot measures on judicial retirement ages, and Tennessee’s vote to allow the governor to appoint judges of the Supreme Court and intermediate appellate court, subject to legislative approval

Extraordinary behavioral entrainment following circadian rhythm bifurcation in mice.

The mammalian circadian timing system uses light to synchronize endogenously generated rhythms with the environmental day. Entrainment to schedules that deviate significantly from 24 h (T24) has been viewed as unlikely because the circadian pacemaker appears capable only of small, incremental responses to brief light exposures. Challenging this view, we demonstrate that simple manipulations of light alone induce extreme plasticity in the circadian system of mice. Firstly, exposure to dim nocturnal illumination (<0.1 lux), rather than completely dark nights, permits expression of an altered circadian waveform wherein mice in light/dark/light/dark (LDLD) cycles "bifurcate" their rhythms into two rest and activity intervals per 24 h. Secondly, this bifurcated state enables mice to adopt stable activity rhythms under 15 or 30 h days (LDLD T15/T30), well beyond conventional limits of entrainment. Continuation of dim light is unnecessary for T15/30 behavioral entrainment following bifurcation. Finally, neither dim light alone nor a shortened night is sufficient for the extraordinary entrainment observed under bifurcation. Thus, we demonstrate in a non-pharmacological, non-genetic manipulation that the circadian system is far more flexible than previously thought. These findings challenge the current conception of entrainment and its underlying principles, and reveal new potential targets for circadian interventions

Maintaining Aura's Orbit Requirements While Performing Orbit Maintenance Maneuvers Containing an Orbit Normal Delta-V Component

The Earth Observing System (EOS) Afternoon Constellation consists of five member missions (GCOM-W1, Aqua, CALIPSO, CloudSat, and Aura), each of which maintain a frozen, sun-synchronous orbit with a 16-day repeating ground track that follows the Worldwide Reference System-2 (WRS-2). Under nominal science operations for Aura, the propulsion system is oriented such that the resultant thrust vector is aligned 13.493 degrees away from the velocity vector along the yaw axis. When performing orbit maintenance maneuvers, the spacecraft performs a yaw slew to align the thrust vector in the appropriate direction. A new Drag Make Up (DMU) maneuver operations scheme has been implemented for Aura alleviating the need for the 13.493 degree yaw slew. The focus of this investigation is to assess the impact that no-slew DMU maneuver operations will have on Aura's Mean Local Time (MLT) which drives the required along track separation between Aura and the constellation members, as well as Aura's frozen orbit properties, eccentricity and argument of perigee. Seven maneuver strategies were analyzed to determine the best operational approach. A mirror pole strategy, with maneuvers alternating at the North and South poles, was implemented operationally to minimize impact to the MLT. Additional analysis determined that the mirror pole strategy could be further modified to include frozen orbit maneuvers and thus maintain both MLT and the frozen orbit properties under noslew operations

A Framework to Manage the Complex Organisation of Collaborating: Its Application to Autonomous Systems

In this paper we present an analysis of the complexities of large group collaboration and its application to develop detailed requirements for collaboration schema for Autonomous Systems (AS). These requirements flow from our development of a framework for collaboration that provides a basis for designing, supporting and managing complex collaborative systems that can be applied and tested in various real world settings. We present the concepts of "collaborative flow" and "working as one" as descriptive expressions of what good collaborative teamwork can be in such scenarios. The paper considers the application of the framework within different scenarios and discuses the utility of the framework in modelling and supporting collaboration in complex organisational structures

Publication Frequency among Faculty in Explicitly Christian Doctoral Programs

Explicitly Ch1istian doctoral programs in professional psychology have proliferated in recent years as part of the larger trend toward professional school training. The current study is an investigation of publication rates among faculty in these programs. Based on an analysis of publication data from 1996 to 2001, faculty in explicitly Christian programs are publishing in psychology journals at rates similar to faculty in other professional schools and programs. No differences were observed between faculty in PhD and PsyD programs. Implications for students selecting doctoral programs are discussed

Recognition of some perfectly orderable graph classes

AbstractThis paper presents new algorithms for recognizing several classes of perfectly orderable graphs. Bipolarizable and P4-simplicial graphs are recognized in O(n3.376) time, improving the previous bounds of O(n4) and O(n5), respectively. Brittle and semi-simplicial graphs are recognized in O(n3) time using a randomized algorithm, and O(n3log2n) time if a deterministic algorithm is required. The best previous time bound for recognizing these classes of graphs is O(m2). Welsh–Powell opposition graphs are recognized in O(n3) time, improving the previous bound of O(n4). HHP-free graphs and maxibrittle graphs are recognized in O(mn) and O(n3.376) time, respectively

Comparative analysis of the human serine hydrolase OVCA2 to the model serine hydrolase homolog FSH1 from S. cerevisiae

Over 100 metabolic serine hydrolases are present in humans with confirmed functions in metabolism, immune response, and neurotransmission. Among potentially clinically relevant but uncharacterized human serine hydrolases is OVCA2, a serine hydrolase that has been linked with a variety of cancer-related processes. Herein, we developed a heterologous expression system for OVCA2 and determined the comprehensive substrate specificity of OVCA2 against two ester substrate libraries. Based on this analysis, OVCA2 was confirmed as a serine hydrolase with a strong preference for long-chain alkyl ester substrates (\u3e10-carbons) and high selectivity against a variety of short, branched, and substituted esters. Substitutional analysis was used to identify the catalytic residues of OVCA2 with a Ser117-His206-Asp179 classic catalytic triad. Comparison of the substrate specificity of OVCA2 to the model homologue FSH1 from Saccharomyces cerevisiae illustrated the tighter substrate selectivity of OVCA2, but their overlapping substrate preference for extended straight-chain alkyl esters. Conformation of the overlapping biochemical properties of OVCA2 and FSH1 was used to model structural information about OVCA2. Together our analysis provides detailed substrate specificity information about a previously, uncharacterized human serine hydrolase and begins to define the biological properties of OVCA2

Synchronous dynamics of zooplankton competitors prevail in temperate lake ecosystems

Although competing species are expected to exhibit compensatory dynamics (negative temporal covariation), empirical work has demonstrated that competitive communities often exhibit synchronous dynamics (positive temporal covariation). This has led to the suggestion that environmental forcing dominates species dynamics; however, synchronous and compensatory dynamics may appear at different length scales and/or at different times, making it challenging to identify their relative importance. We compiled 58 long-term datasets of zooplankton abundance in north-temperate and sub-tropical lakes and used wavelet analysis to quantify general patterns in the times and scales at which synchronous/compensatory dynamics dominated zooplankton communities in different regions and across the entire dataset. Synchronous dynamics were far more prevalent at all scales and times and were ubiquitous at the annual scale. Although we found compensatory dynamics in approximately 14% of all combinations of time period/scale/lake, there were no consistent scales or time periods during which compensatory dynamics were apparent across different regions. Our results suggest that the processes driving compensatory dynamics may be local in their extent, while those generating synchronous dynamics operate at much larger scales. This highlights an important gap in our understanding of the interaction between environmental and biotic forces that structure communities

Copper-free click chemistry for the in situ crosslinking of photodegradable star polymers

Bifunctional, fluorinated cyclooctynes were used for the in situ click crosslinking of azide-terminated photodegradable star polymers, yielding photodegradable polymeric model networks with well-defined structures and tunable gelation times