A 15 year slow-slip event on the Sunda megathrust offshore Sumatra

In the Banyak Islands of Sumatra, coral microatoll records reveal a 15 year-long reversal of interseismic vertical displacement from subsidence to uplift between 1966 and 1981. To explain these coral observations, we test four hypotheses, including regional sea level changes and various tectonic mechanisms. Our results show that the coral observations likely reflect a 15 year-long slow-slip event (SSE) on the Sunda megathrust. This long-duration SSE exceeds the duration of previously reported SSEs and demonstrates the importance of multidecade geodetic records in illuminating the full spectrum of megathrust slip behavior at subduction zones

isolateR: an R package for generating microbial libraries from Sanger sequencing data

Motivation: Sanger sequencing of taxonomic marker genes (e.g. 16S/18S/ITS/rpoB/cpn60) represents the leading method for identifying a wide range of microorganisms including bacteria, archaea, and fungi. However, the manual processing of sequence data and limitations associated with conventional BLAST searches impede the efficient generation of strain libraries essential for cataloging microbial diversity and discovering novel species. Results: isolateR addresses these challenges by implementing a standardized and scalable three-step pipeline that includes: (1) automated batch processing of Sanger sequence files, (2) taxonomic classification via global alignment to type strain databases in accordance with the latest international nomenclature standards, and (3) straightforward creation of strain libraries and handling of clonal isolates, with the ability to set customizable sequence dereplication thresholds and combine data from multiple sequencing runs into a single library. The tool’s user-friendly design also features interactive HTML outputs that simplify data exploration and analysis. Additionally, in silico benchmarking done on two comprehensive human gut genome catalogues (IMGG and Hadza hunter-gather populations) showcase the proficiency of isolateR in uncovering and cataloging the nuanced spectrum of microbial diversity, advocating for a more targeted and granular exploration within individual hosts to achieve the highest strain-level resolution possible when generating culture collections. Availability and implementation: isolateR is available at: https://github.com/bdaisley/isolateR

The ENJOY MAP for HEALTH: Exercise interveNtion outdoor proJect in the cOmmunitY for older people—More Active People for HEALTHier communities: a study protocol

Background: Physical activity is important to maintain health in older age, with physical activity in the outdoors providing mental and physical health benefits for all age groups. One way by which older people can engage in physical activity in the outdoors is through using suitable age-friendly outdoor exercise equipment, the Seniors Exercise Park. The ENJOY MAP for HEALTH aims to evaluate the effect of the Seniors Exercise Park installation and associated capacity building activities on park visitation, park-based physical activity by older people and delivery of community physical activity programs. Method: This study is a quasi-experimental (natural experiment) with pre and post study design evaluating the effect of age-friendly outdoor spaces with specialised outdoor exercise equipment on older people’s physical activity and wellbeing in six Victorian municipalities (local governments/councils). Each council will undergo four stages (site construction and development, promotion and marketing, capacity building and training, evaluation and sustainability). Several activities and methods will be employed from stage one through stage four to evaluate the potential impact of the age-friendly outdoor spaces on physical activity and wellbeing and will comprise the following elements: site observation and equipment utilisation, face to face intercept surveys, development of an online access monitor and community building activities. Discussion: The project is expected to result in a significant change in the physical outdoor environment for the participating councils and communities whereby older people and other community members will be able to engage in safe physical and social activity programs, socialise more and hence improve the overall wellbeing of older people. Trial registration: This trial is retrospectively registered with the Australian New Zealand Clinical Trials Registry. Trial registration number ACTRN12621000965808. Date registered 23/07/2021

The role of the RACK1 ortholog Cpc2p in modulating pheromone-induced cell cycle arrest in fission yeast

The detection and amplification of extracellular signals requires the involvement of multiple protein components. In mammalian cells the receptor of activated C kinase (RACK1) is an important scaffolding protein for signal transduction networks. Further, it also performs a critical function in regulating the cell cycle by modulating the G1/S transition. Many eukaryotic cells express RACK1 orthologs, with one example being Cpc2p in the fission yeast Schizosaccharomyces pombe. In contrast to RACK1, Cpc2p has been described to positively regulate, at the ribosomal level, cells entry into M phase. In addition, Cpc2p controls the stress response pathways through an interaction with Msa2p, and sexual development by modulating Ran1p/Pat1p. Here we describe investigations into the role, which Cpc2p performs in controlling the G protein-mediated mating response pathway. Despite structural similarity to Gβ-like subunits, Cpc2p appears not to function at the G protein level. However, upon pheromone stimulation, cells overexpressing Cpc2p display substantial cell morphology defects, disorientation of septum formation and a significantly protracted G1 arrest. Cpc2p has the potential to function at multiple positions within the pheromone response pathway. We provide a mechanistic interpretation of this novel data by linking Cpc2p function, during the mating response, with its previous described interactions with Ran1p/Pat1p. We suggest that overexpressing Cpc2p prolongs the stimulated state of pheromone-induced cells by increasing ste11 gene expression. These data indicate that Cpc2p regulates the pheromone-induced cell cycle arrest in fission yeast by delaying cells entry into S phase

Dialogue across Indigenous, local and scientific knowledge systems reflecting on the IPBES Assessment on Pollinators, Pollination and Food Production

The Dialogue across Indigenous, local and scientific knowledge systems reflecting on the IPBES Assessment on Pollinators, Pollination and Food Production report presents the main outcomes of a Dialogue across Indigenous, local and scientific knowledge systems that revisited and reflected on the key messages derived from the Assessment Report on Pollinators, Pollination and Food Production of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES). The Dialogue was hosted from the 21st to the 25th of January 2019 by the Karen community of Hin Lad Nai, Chiang Rai, Thailand, and it was co-convened and jointly designed by the Inter Mountain Peoples Education and Culture in Thailand Association (IMPECT) and Pgakenyaw Association for Sustainable Development (PASD) together with SwedBio at the Stockholm Resilience Centre and UNESCO Natural Science Sector

Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9-13 Years

IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p < 0.001). HOMA-IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF-I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA-IR (pInteraction < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF-I and Ct.Ar via FFST in the total cohort (βIndirect Effect = 0.321, p < 0.001). However, this relationship was moderated in the children with high (βIndirect Effect = 0.200, p < 0.001) versus normal (βIndirect Effect = 0.408, p < 0.001) HOMA-IR. These data implicate insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed

In situ identification of Gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid A

Acknowledgment to AAAS for publishing this manuscript with DOI 10.1126/scitranslmed.aal0033 https://www.science.org/doi/10.1126/scitranslmed.aal0033Respiratory infections in mechanically ventilated patients caused by Gram-negative bacteria are a major cause of morbidity. Rapid and unequivocal determination of the presence, localization, and abundance of bacteria is criti cal for positive resolution of the infections and could be used for patient stratification and for monitoring treat ment efficacy. Here, we developed an in situ approach to visualize Gram-negative bacterial species and cellular infiltrates in distal human lungs in real time. We used optical endomicroscopy to visualize a water-soluble optical imaging probe based on the antimicrobial peptide polymyxin conjugated to an environmentally sensitive fluoro phore. The probe was chemically stable and nontoxic and, after in-human intrapulmonary microdosing, enabled the specific detection of Gram-negative bacteria in distal human airways and alveoli within minutes. The results suggest that pulmonary molecular imaging using a topically administered fluorescent probe targeting bacterial lipid A is safe and practical, enabling rapid in situ identification of Gram-negative bacteria in humans.This work was supported by Wellcome Trust, the Department of Health Healthcare Innovation Challenge Fund (HICF-0510-069), and the Engineering and Physical Sciences Research Council Interdisciplinary Research Collaboration “Proteus” (EP/K03197X/1). The GMP activities were supported by the National Institute for Health Research (NIHR) BRC GMP Unit at Guy’s and St. Thomas’ NHS Foundation Trust and NIHR Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London

Genetics of callous-unemotional behavior in children

Callous-unemotional behavior (CU) is currently under consideration as a subtyping index for conduct disorder diagnosis. Twin studies routinely estimate the heritability of CU as greater than 50%. It is now possible to estimate genetic influence using DNA alone from samples of unrelated individuals, not relying on the assumptions of the twin method. Here we use this new DNA method (implemented in a software package called Genome-wide Complex Trait Analysis, GCTA) for the first time to estimate genetic influence on CU. We also report the first genome-wide association (GWA) study of CU as a quantitative trait. We compare these DNA results to those from twin analyses using the same measure and the same community sample of 2,930 children rated by their teachers at ages 7, 9 and 12. GCTA estimates of heritability were near zero, even though twin analysis of CU in this sample confirmed the high heritability of CU reported in the literature, and even though GCTA estimates of heritability were substantial for cognitive and anthropological traits in this sample. No significant associations were found in GWA analysis, which, like GCTA, only detects additive effects of common DNA variants. The phrase ‘missing heritability’ was coined to refer to the gap between variance associated with DNA variants identified in GWA studies versus twin study heritability. However, GCTA heritability, not twin study heritability, is the ceiling for GWA studies because both GCTA and GWA are limited to the overall additive effects of common DNA variants, whereas twin studies are not. This GCTA ceiling is very low for CU in our study, despite its high twin study heritability estimate. The gap between GCTA and twin study heritabilities will make it challenging to identify genes responsible for the heritability of CU