Propagation of hippocampal ripples to the neocortex by way of a subiculum-retrosplenial pathway

Bouts of high frequency activity known as sharp wave ripples (SPW-Rs) facilitate communication between the hippocampus and neocortex. However, the paths and mechanisms by which SPW-Rs broadcast their content are not well understood. Due to its anatomical positioning, the granular retrosplenial cortex (gRSC) may be a bridge for this hippocampo-cortical dialogue. Using silicon probe recordings in awake, head-fixed mice, we show the existence of SPW-R analogues in gRSC and demonstrate their coupling to hippocampal SPW-Rs. gRSC neurons reliably distinguished different subclasses of hippocampal SPW-Rs according to ensemble activity patterns in CA1. We demonstrate that this coupling is brain state-dependent, and delineate a topographically-organized anatomical pathway via VGlut2-expressing, bursty neurons in the subiculum. Optogenetic stimulation or inhibition of bursty subicular cells induced or reduced responses in superficial gRSC, respectively. These results identify a specific path and underlying mechanisms by which the hippocampus can convey neuronal content to the neocortex during SPW-Rs

An empirically-based characterization and quantification of information seeking through mailing lists during Open Source developers' software evolution

Context Several authors have proposed information seeking as an appropriate perspective for studying software evolution. Empirical evidence in this area suggests that substantial time delays can accrue, due to the unavailability of required information, particularly when this information must travel across geographically distributed sites. Objective As a first step in addressing the time delays that can occur in information seeking for distributed Open Source (OS) programmers during software evolution, this research characterizes the information seeking of OS developers through their mailing lists. Method A longitudinal study that analyses 17 years of developer mailing list activity in total, over 6 different OS projects is performed, identifying the prevalent information types sought by developers, from a qualitative, grounded analysis of this data. Quantitative analysis of the number-of-responses and response time-lag is also performed. Results The analysis shows that Open Source developers are particularly implementation centric and team focused in their use of mailing lists, mirroring similar findings that have been reported in the literature. However novel findings include the suggestion that OS developers often require support regarding the technology they use during development, that they refer to documentation fairly frequently and that they seek implementation-oriented specifics based on system design principles that they anticipate in advance. In addition, response analysis suggests a large variability in the response rates for different types of questions, and particularly that participants have difficulty ascertaining information on other developer's activities. Conclusion The findings provide insights for those interested in supporting the information needs of OS developer communities: They suggest that the tools and techniques developed in support of co-located developers should be largely mirrored for these communities: that they should be implementation centric, and directed at illustrating "how" the system achieves its functional goals and states. Likewise they should be directed at determining the reason for system bugs: a type of question frequently posed by OS developers but less frequently responded to

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Elucidation of mechanisms by which maize Ac and Ds elements induce chromosome breakage

SIGLEAvailable from British Library Document Supply Centre- DSC:DX177297 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Requirement of sense transcription for homology-dependent virus resistance and trans-inactivation

International audienc