Asymmetric interactions in the adenosine-binding pockets of the MS2 coat protein dimer

BACKGROUND: The X-ray structure of the MS2 coat protein-operator RNA complex reveals the existence of quasi-synmetric interactions of adenosines -4 and -10 in pockets formed on different subunits of the coat protein dimer. Both pockets utilize the same five amino acid residues, namely Val29, Thr45, Ser47, Thr59, and Lys61. We call these sites the adenosine-binding pockets. RESULTS: We present here a heterodimer complementation analysis of the contributions of individual A-pocket amino acids to the binding of A-4 and A-10 in different halves of the dimer. Various substitutions of A-pocket residues were introduced into one half of single-chain coat protein heterodimers where they were tested for their abilities to complement Y85H or T91I substitutions (defects in the A-4 and A-10 half-sites, respectively) present in the other dimer half. CONCLUSIONS: These experiments provide functional tests of interactions predicted from structural analyses, demonstrating the importance of certain amino acid-nucleotide contacts observed in the crystal structure, and showing that others make little or no contribution to the stability of the complex. In summary, Val29 and Lys61 form important stabilizing interactions with both A-4 and A-10. Meanwhile, Ser47 and Thr59 interact primarily with A-10. The important interactions with Thr45 are restricted to A-4

Altered patterns of gene duplication and differential gene gain and loss in fungal pathogens

<p>Abstract</p> <p>Background</p> <p>Duplication, followed by fixation or random loss of novel genes, contributes to genome evolution. Particular outcomes of duplication events are possibly associated with pathogenic life histories in fungi. To date, differential gene gain and loss have not been studied at genomic scales in fungal pathogens, despite this phenomenon's known importance in virulence in bacteria and viruses.</p> <p>Results</p> <p>To determine if patterns of gene duplication differed between pathogens and non-pathogens, we identified gene families across nine euascomycete and two basidiomycete species. Gene family size distributions were fit to power laws to compare gene duplication trends in pathogens <it>versus </it>non-pathogens. Fungal phytopathogens showed globally altered patterns of gene duplication, as indicated by differences in gene family size distribution. We also identified sixteen examples of gene family expansion and five instances of gene family contraction in pathogenic lineages. Expanded gene families included those predicted to be important in melanin biosynthesis, host cell wall degradation and transport functions. Contracted families included those encoding genes involved in toxin production, genes with oxidoreductase activity, as well as subunits of the vacuolar ATPase complex. Surveys of the functional distribution of gene duplicates indicated that pathogens show enrichment for gene duplicates associated with receptor and hydrolase activities, while euascomycete pathogens appeared to have not only these differences, but also significantly more duplicates associated with regulatory and carbohydrate binding functions.</p> <p>Conclusion</p> <p>Differences in the overall levels of gene duplication in phytopathogenic species <it>versus </it>non-pathogenic relatives implicate gene inventory flux as an important virulence-associated process in fungi. We hypothesize that the observed patterns of gene duplicate enrichment, gene family expansion and contraction reflect adaptation within pathogenic life histories. These adaptations were likely shaped by ancient, as well as contemporary, intimate associations with monocot hosts.</p

Predictive Analytics Supporting Labor Market Success: A Career Explorer for Job Seekers and Workforce Professionals in Michigan

Career Explorer provides customized career exploration tools for workforce development staff and job seekers in Michigan. There are separate Career Explorer modules for mediated staff services and self-service by job seekers. The system was developed by the Michigan Center for Data and Analytics in collaboration with the W.E. Upjohn Institute for Employment Research and Michigan Works! Southwest. It was funded by the U.S. Department of Labor’s Office of Workforce Investment and the Schmidt Futures foundation’s Data for the American Dream (D4AD) project. In this paper, we describe specifications of the models behind the frontline-staff-mediated version of Career Explorer, which are based on program administrative data, applying data-science methods for predictive analytics. We also describe the self-service Career Explorer, which provides customized labor market information based on published Bureau of Labor Statistics data. Career Explorer became an active feature of Michigan’s online reemployment-services system in June 2021

Care team and practice-level implementation strategies to optimize pediatric collaborative care: Study protocol for a cluster-randomized hybrid type III trial

BACKGROUND: Implementation facilitation is an effective strategy to support the implementation of evidence-based practices (EBPs), but our understanding of multilevel strategies and the mechanisms of change within the black box of implementation facilitation is limited. This implementation trial seeks to disentangle and evaluate the effects of facilitation strategies that separately target the care team and leadership levels on implementation of a collaborative care model in pediatric primary care. Strategies targeting the provider care team (TEAM) should engage team-level mechanisms, and strategies targeting leaders (LEAD) should engage organizational mechanisms. METHODS: We will conduct a hybrid type 3 effectiveness-implementation trial in a 2 × 2 factorial design to evaluate the main and interactive effects of TEAM and LEAD and test for mediation and moderation of effects. Twenty-four pediatric primary care practices will receive standard REP training to implement Doctor-Office Collaborative Care (DOCC) and then be randomized to (1) Standard REP only, (2) TEAM, (3) LEAD, or (4) TEAM + LEAD. Implementation outcomes are DOCC service delivery and change in practice-level care management competencies. Clinical outcomes are child symptom severity and quality of life. DISCUSSION: This statewide trial is one of the first to test the unique and synergistic effects of implementation strategies targeting care teams and practice leadership. It will advance our knowledge of effective care team and practice-level implementation strategies and mechanisms of change. Findings will support efforts to improve common child behavioral health conditions by optimizing scale-up and sustainment of CCMs in a pediatric patient-centered medical home. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04946253 . Registered June 30, 2021

Measuring Health Related Quality of Life for Dengue Patients in Iquitos, Peru

Previous studies measuring the health-related quality of life (HRQoL) of individuals with dengue focused on treatment seeking populations. However, the vast majority of global dengue cases are unlikely to be detected by health systems. Representative measurements of HRQoL should therefore include patients with disease not likely to trigger treatment-seeking behavior. This study based in Iquitos, Peru used the Quality of Wellbeing Scale-Self Administered, a survey that enquires about not only physical health, but also psychological health, self-care, mobility, and usual social activities, and rates HRQoL between 0 (death) and 1 (optimum function), to evaluate the impact of dengue on HRQoL. In order to enroll treatment and non treatment-seeking participants, three modalities of participant recruitment were used. In addition to clinic and community-based febrile surveillance, a contact-cluster methodology was also employed to identify infected individuals less likely to seek treatment. We measured changes in HRQoL and identified common areas of health impairment in 73 virologically confirmed dengue cases at 3 time points during the participant\u27s illness; the early-acute (days 0-6 post symptom onset), late-acute (days 7-20), and convalescent illness phases (days 21 +). Participants reported HRQoL related impairments at significantly higher frequency during the early-acute versus convalescent illness phase (Fisher\u27s exact: P\u3c0.01). There was substantial heterogeneity in scores during each illness phase with median scores in the early-acute, late-acute and convalescent phases of 0.56 (IQR: 0.41-0.64), 0.70 (IQR: 0.57-0.94), and 1 (IQR: 0.80-1.00), respectively. In all illness phases participants recruited in clinics had on average the lowest HRQoL scores where as those recruited in the contact clusters had the highest. Only 1 individual who was recruited in the contact-clusters had no reduction in HRQoL score during their illness. These data illustrate that dengue should be considered as a disease that may have significant implications for not only physical health but also psychological health and social functioning. The impact of dengue on the HRQoL of non-treatment-seeking individuals, although lower than the impact among treatment-seeking individuals, is not necessarily trivial

Turning Transfer Inside Out: The Affordances of Virtual Worlds and Mobile Devices in Real World Contexts for Teaching About Causality Across Time and Distance in Ecosystems

Reasoning about ecosystems includes consideration of causality over temporal and spatial distances; yet learners typically focus on immediate time frames and local contexts. Teaching students to reason beyond these boundaries has met with some success based upon tests that cue students to the types of reasoning required. Virtual worlds offer an opportunity to assess what students actually do in a simulated context. Beyond this, mobile devices make it possible to scaffold and assess learning in the real world. Situating learning outside, in the target contexts, bypasses many of the challenges of transfer. A study investigated the learning of fifth and sixth graders (n = 38) while they used a virtual world called EcoMUVE, designed to support learning of ecosystems concepts and complex causal dynamics, and mobile broadband device (MBDs) components, designed to assess and support learning and transfer in a real pond ecosystem. The experiences of two classes were contrasted as reference populations; one class participated in the MBD experience first, followed by the learning components in EcoMUVE; the other participated in EcoMUVE first, followed by the MBD components. Rich and triangulated data was collected to illuminate how students experienced and responded to the curriculum components. Both classes made learning gains in EcoMUVE. Students who completed EcoMUVE prior to their MBD experience transferred concepts to their pond explorations. Both classes made learning gains at the pond following the MBD support and revealed more expert reasoning about the importance of change over time and distant drivers in ecosystem dynamics

Preparation, structured deliberate practice and decision making in elite level football: The case study of Gary Neville (Manchester United FC and England)

Decision making in elite level sporting competition is often regarded as distinguishing success from failure. As an intricate brain-based process it is unlike other physical processes because it is invisible and is typically only evidenced after the event. This case study shows how an individual achieved great success in elite level professional football through consistent positive decision making on and off the field of play. Through prolonged interviewing, Gary Neville, a player from Manchester United Football Club, explored personal behaviours, the structure and activities of deliberate practice and his professional choices in match preparation. His career-long devotion to purposeful organised practice was focused on cognition, physical preparation, context-relative physical action and refined repetition to optimise his mental comfort while enhancing his match day performances. This approach was underpinned by diligent personal and collective organisation and by concerted action. Results provide an insight into the categorical nature of his deliberate practice, sport-specific information processing and match-based decision making. At the operational level, his process was mediated by a complex mental representation of ongoing and anticipated game situations; these representations were continuously updated during each match. Allowing for the limitations of the design, implications are provided for developmental and educational coaching, match preparation, deliberate practice activity and improved use of the performance analysis software packages in professional football

Second Human Case of Cache Valley Virus Disease

We document the second known case of Cache Valley virus disease in a human. Cache Valley virus disease is rarely diagnosed in North America, in part because laboratories rarely test for it. Its true incidence, effect on public health, and full clinical spectrum remain to be determined