Microbial laboratory evolution in the era of genome-scale science

Advances in DNA sequencing, high-throughput technologies, and genetic manipulation systems have enabled empirical studies of the molecular and genomic bases of adaptive evolution. This review discusses key insights learned from direct observation of the evolution process

Potentiality in Biology

We take the potentialities that are studied in the biological sciences (e.g., totipotency) to be an important subtype of biological dispositions. The goal of this paper is twofold: first, we want to provide a detailed understanding of what biological dispositions are. We claim that two features are essential for dispositions in biology: the importance of the manifestation process and the diversity of conditions that need to be satisfied for the disposition to be manifest. Second, we demonstrate that the concept of a disposition (or potentiality) is a very useful tool for the analysis of the explanatory practice in the biological sciences. On the one hand it allows an in-depth analysis of the nature and diversity of the conditions under which biological systems display specific behaviors. On the other hand the concept of a disposition may serve a unificatory role in the philosophy of the natural sciences since it captures not only the explanatory practice of biology, but of all natural sciences. Towards the end we will briefly come back to the notion of a potentiality in biology

Sustainable waiting time reductions after introducing the STAT model for access and triage: 12-month follow up of a stepped wedge cluster randomised controlled trial

Abstract Background Timely access is a challenge for providers of outpatient and community-based health services, as seen by the often lengthy waiting lists to manage demand. The Specific Timely Appointments for Triage (STAT) model, an alternative approach for managing access and triage, reduced waiting time by 34% in a stepped wedge cluster randomised controlled trial involving 8 services and more than 3000 participants. Follow up periods ranged from 3 to 10 months across the participating services in accordance with the stepped wedge design. This study aimed to determine whether outcomes were sustained for a full 12 months after implementation of the STAT model at each site. Methods Routinely collected service data were obtained for a total of 12 months following implementation of the STAT model at each of the 8 services that participated in a stepped wedge cluster randomised controlled trial. The primary outcome was time to first appointment. Secondary outcomes included non-attendance rates, time to second appointment and service use over 12 weeks. Outcomes were compared to pre-intervention data from the original trial, modelled using generalised linear mixed effects models accounting for clustering of sites. Results A 29% reduction in waiting time could be attributed to STAT over 12 months, compared to 34% in the original trial. A reduction in variability in waiting time was sustained. There were no significant changes in time to second appointment or in the number of missed appointments in the extended follow up period. Conclusions STAT is an effective strategy for reducing waiting time in community-based outpatient services. At 12 months, small reductions in the overall effect are apparent, but reductions in variability are sustained, suggesting that people who previously waited the longest benefit most from the STAT model. Trial registration This is a 12-month follow up of a stepped wedge cluster randomised controlled trial that was registered with the Australia and New Zealand Clinical Trials Registry (ACTRN12615001016527). </jats:sec

The Phyre2 web portal for protein modeling, prediction and analysis

Phyre2 is a suite of tools available on the web to predict and analyze protein structure, function and mutations. The focus of Phyre2 is to provide biologists with a simple and intuitive interface to state-of-the-art protein bioinformatics tools. Phyre2 replaces Phyre, the original version of the server for which we previously published a paper in Nature Protocols. In this updated protocol, we describe Phyre2, which uses advanced remote homology detection methods to build 3D models, predict ligand binding sites and analyze the effect of amino acid variants (e.g., nonsynonymous SNPs (nsSNPs)) for a user's protein sequence. Users are guided through results by a simple interface at a level of detail they determine. This protocol will guide users from submitting a protein sequence to interpreting the secondary and tertiary structure of their models, their domain composition and model quality. A range of additional available tools is described to find a protein structure in a genome, to submit large number of sequences at once and to automatically run weekly searches for proteins that are difficult to model. The server is available at http://www.sbg.bio.ic.ac.uk/phyre2. A typical structure prediction will be returned between 30 min and 2 h after submission

The economics of Theocracy

This paper models theocracy as a regime where the clergy in power retains knowledge of the cost of political production but which is potentially incompetent or corrupt. This is contrasted with a secular regime where government is contracted out to a secular ruler, and hence the church loses the possibility to observe costs and creates for itself a hidden-information agency problem. The church is free to choose between regimes – a make-or-buy choice – and we look for the range of environmental parameters that are most conducive to the superiority of theocracy and therefore to its occurrence and persistence, despite its disabilities. Numerical solution of the model indicates that the optimal environment for a theocracy is likely to be one in which the “bad” (high-cost) state is disastrously bad but the probability of its occurrence is not very high. A broad review of the historical evidence yields some suggestive support to the predictions of the model. Finally, the model is shown to be applicable to the make-or-buy-government choices of other groups, such as organized labor and the military

ADPβS evokes microglia activation in the rabbit retina in vivo

To investigate whether stimulation of purinergic P2Y1 receptors modulates the activation of microglial and Müller glial cells in the rabbit retina in vivo, adenosine 5-O-(2-thiodiphosphate) (ADPβS; 2 mM in 100 μl saline), a non-hydrolyzable ADP analogue, was intravitreadly applied into control eyes or onto retinas that were experimentally detached from the pigment epithelium. Both retinal detachment and application of ADPßS onto control retinas induced phenotype alterations of the microglial cells (decrease of soma size, retraction of cell processes) and had no influence on microglial cell density. ADPßS application onto detached retinas accelerated the process retraction and resulted in a strongly decreased density of microglial cells. The effects of ADPßS on microglia density and phenotype in detached retinas were partially reversed by co-application of the selective inhibitor of P2Y1 receptors, MRS-2317 (3 mM in 100 μl saline). ADPßS apparently did not influence Müller cell gliosis, as determined by electrophysiological and calcium imaging records. It is concluded that rabbit retinal microglial cells express functional P2Y1 receptors in vivo, and that activation of these receptors stimulates phenotype alterations that are characteristical for microglia activation

The Hong Kong mental morbidity survey: background and study design

Mental disorders are highly prevalent conditions with immense disease burden. To inform health and social services policy formulation, local psychiatric epidemiological data are required. The Hong Kong Mental Morbidity Survey is a 3-year population-based study in which 5700 community-dwelling Chinese adults aged between 16 and 75 years were interviewed with the aim of evaluating the prevalence, co-morbidity, functional impairment, physical morbidity, and social determinants of significant mental disorders in the population. This paper describes the background and design of the survey, and is the first territory-wide psychiatric epidemiological study in Hong Kong. 精神障礙非常普遍，且對社會造成巨大的疾病負擔。收集本地精神病流行病學資料，對計劃相關的衛生及社會服務政策至為重要。香港精神健康調查是一個為期3年，以人口為基礎的大型研究，透過對5700名介乎16歲至75歲之華裔市民進行精神健康評估，檢視重要的精神障礙的現患率、共病、功能障礙、身體疾病以及社會決定因素。本文闡述這項首個全港大型精神病流行病研究的背景和設計。published_or_final_versio

Nitrogen transfer from forage legumes to nine neighbouring plants in a multi-species grassland

Legumes play a crucial role in nitrogen supply to grass-legume mixtures for ruminant fodder. To quantify N transfer from legumes to neighbouring plants in multi-species grasslands we established a grass-legume-herb mixture on a loamy-sandy site in Denmark. White clover (Trifolium repens L.), red clover (Trifolium pratense L.) and lucerne (Medicago sativa L.) were leaf-labelled with 15N enriched urea during one growing season. N transfer to grasses (Lolium perenne L. and xfestulolium), white clover, red clover, lucerne, birdsfoot trefoil (Lotus corniculatus L.), chicory (Cichorium intybus L.), plantain (Plantago lanceolata L.), salad burnet (Sanguisorba minor L.)and caraway (Carum carvi L.) was assessed. Neighbouring plants contained greater amounts of N derived from white clover (4.8 gm-2) compared with red clover (2.2 gm-2) and lucerne (1.1 gm-2). Grasses having fibrous roots received greater amounts of N from legumes than dicotyledonous plants which generally have taproots. Slurry application mainly increased N transfer from legumes to grasses. During the growing season the three legumes transferred approximately 40 kg N ha-1 to neighbouring plants. Below-ground N transfer from legumes to neighbouring plants differed among nitrogen donors and nitrogen receivers and may depend on root characteristics and regrowth strategies of plant species in the multi-species grassland

The Use of Social Media for Dissemination of Research Evidence to Health and Social Care Practitioners: Protocol for a Systematic Review.

BACKGROUND: Effective dissemination of research to health and social care practitioners enhances clinical practice and evidence-based care. Social media use has potential to facilitate dissemination to busy practitioners. OBJECTIVE: This is a protocol for a systematic review that will quantitatively synthesize evidence of the effectiveness of social media, compared with no social media, for dissemination of research evidence to health and social care practitioners. Social media platforms, formats, and sharing mechanisms used for effective dissemination of research evidence will also be identified and compared. METHODS: Electronic database searches (MEDLINE, PsycINFO, CINAHL, ERIC, LISTA, and OpenGrey) will be conducted from January 1, 2010, to January 10, 2023, for studies published in English. Randomized, nonrandomized, pre-post study designs or case studies evaluating the effect of social media on dissemination of research evidence to postregistration health and social care practitioners will be included. Studies that do not involve social media or dissemination or those that evaluate dissemination of nonresearch information (eg, multisource educational materials) to students or members of the public only, or without quantitative data on outcomes of interest, will be excluded. Screening will be carried out by 2 independent reviewers. Data extraction and quality assessment, using either the Cochrane tool for assessing risk of bias or the Newcastle-Ottawa Scale, will be completed by 2 independent reviewers. Outcomes of interest will be reported in 4 domains (reach, engagement, dissemination, and impact). Data synthesis will include quantitative comparisons using narrative text, tables, and figures. A meta-analysis of standardized pooled effects will be undertaken, and subgroup analyses will be applied, if appropriate. RESULTS: Searches and screening will be completed by the end of May 2023. Data extraction and analyses will be completed by the end of July 2023, after which findings will be synthesized and reported by the end of October 2023. CONCLUSIONS: This systematic review will summarize the evidence for the effectiveness of social media for the dissemination of research evidence to health and social care practitioners. The limitations of the evidence may include multiple outcomes or methodological heterogeneity that limit meta-analyses, potential risk of bias in included studies, and potential publication bias. The limitations of the study design may include potential insensitivity of the electronic database search strategy. The findings from this review will inform the dissemination practice of health and care research. TRIAL REGISTRATION: PROSPERO CRD42022378793; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=378793. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45684