Is it feasible to estimate radiosonde biases from interlaced measurements?

Upper-air measurements of essential climate variables (ECVs), such as temperature, are crucial for climate monitoring and climate change detection. Because of the internal variability of the climate system, many decades of measurements are typically required to robustly detect any trend in the climate data record. It is imperative for the records to be temporally homogeneous over many decades to confidently estimate any trend. Historically, records of upper-air measurements were primarily made for short-term weather forecasts and as such are seldom suitable for studying long-term climate change as they lack the required continuity and homogeneity. Recognizing this, the Global Climate Observing System (GCOS) Reference Upper-Air Network (GRUAN) has been established to provide reference-quality measurements of climate variables, such as temperature, pressure, and humidity, together with well-characterized and traceable estimates of the measurement uncertainty. To ensure that GRUAN data products are suitable to detect climate change, a scientifically robust instrument replacement strategy must always be adopted whenever there is a change in instrumentation. By fully characterizing any systematic differences between the old and new measurement system a temporally homogeneous data series can be created. One strategy is to operate both the old and new instruments in tandem for some overlap period to characterize any inter-instrument biases. However, this strategy can be prohibitively expensive at measurement sites operated by national weather services or research institutes. An alternative strategy that has been proposed is to alternate between the old and new instruments, so-called interlacing, and then statistically derive the systematic biases between the two instruments. Here we investigate the feasibility of such an approach specifically for radiosondes, i.e. flying the old and new instruments on alternating days. Synthetic data sets are used to explore the applicability of this statistical approach to radiosonde change management

Building global capacity for conducting operational research using the SORT IT model: where and who?

This paper is an output of the Structured Operational Research and Training Initiative (SORT IT), a global partnership led by the Special Program for Research and Training in Tropical Diseases at the World Health Organization (WHO/TDR), Geneva, Switzerland.Setting. Research capacity is weakest in low and middle-income countries (LMICs) where operational research is highly relevant and needed. Structured Operational Research and Training Initiative (SORT IT) courses have been developed to train participants to conduct and publish operational research and influence policy and practice. Twenty courses were completed in Asia, Africa, Europe and the South Pacific between 2009 and 2014. Objectives. In the 20 completed SORT IT courses, to assess where the research was conducted, who was trained, who became facilitators in subsequent courses and course outcomes. Design. A cohort study of completed SORT IT courses. Results. There were 236 participants (41% female) including 64 nationalities who conducted research in 59 countries, mostly from Asia and Africa (mean course duration = 9.7 months). Most participants (68%) were from government health programs and non-governmental agencies. A total of 213(90%) participants completed all milestones successfully with 41(19%) becoming subsequent course facilitators, 88% of whom were from LMICs. Of 228 manuscripts submitted to scientific journals, 197(86%) were either published or in press; in 86%, the principal investigator (first author) was a LMIC national. Papers were published in 23 scientific journals (impact factor 0.5–4.4) and covered 21 disease categories (median publication time = 5.7 months). Published papers (186) had 94,794 cumulative article views/downloads. Article views/downloads for immediate open access articles were double those from closed access journals. Conclusion.  The SORT IT model has been effective in training personnel to produce relevant operational research in LMICs. It merits continued commitment and support for further scale-up and development.Publisher PDFPeer reviewe

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Dual role of Miro protein clusters in mitochondrial cristae organisation and ER-Mitochondria Contact Sites

Mitochondrial Rho (Miro) GTPases localize to the outer mitochondrial membrane and are essential machinery for the regulated trafficking of mitochondria to defined subcellular locations. However, their sub-mitochondrial localization and relationship with other critical mitochondrial complexes remains poorly understood. Here, using super-resolution fluorescence microscopy, we report that Miro proteins form nanometer-sized clusters along the mitochondrial outer membrane in association with the Mitochondrial Contact Site and Cristae Organizing System (MICOS). Using knockout mouse embryonic fibroblasts (MEF) we show that Miro1 and Miro2 are required for normal mitochondrial cristae architecture and endoplasmic reticulum-mitochondria contacts sites (ERMCS). Further, we show that Miro couples MICOS to TRAK motor protein adaptors to ensure the concerted transport of the two mitochondrial membranes and the correct distribution of cristae on the mitochondrial membrane. The Miro nanoscale organization, association with MICOS complex and regulation of ERMCS reveal new levels of control of the Miro GTPases on mitochondrial functionality

Beneath the radar: immune-evasive cell sources for stroke therapy

Stem cell therapy is an emerging treatment paradigm for stroke patients with remaining neurological deficits. While allogeneic cell transplants overcome the manufacturing constraints of autologous grafts, they can be rejected by the recipient's immune system, which identifies foreign cells through the human leukocyte antigen (HLA) system. The heterogeneity of HLA molecules in the human population would require a very high number of cell lines, which may still be inadequate for patients with rare genetic HLAs. Here, we outline key progress in genetic HLA engineering in pluripotent stem and derived cells to evade the host's immune system, reducing the number of allogeneic cell lines required, and examine safety measures explored in both preclinical studies and upcoming clinical trials.ISSN:1471-499XISSN:1471-491

Platelets bridging the gap between gut dysbiosis and neuroinflammation in stress-linked disorders: A narrative review.

In this narrative review, we examine the association between gut dysbiosis, neuroinflammation, and stress-linked disorders, including depression, anxiety, and post-traumatic stress disorder (PTSD), and investigate whether tryptophan (TRP) metabolism and platelets play a role in this association. The mechanisms underlying the aetiology of stress-linked disorders are complex and not yet completely understood. However, a potential link between chronic inflammation and these disorders may potentially be found in TRP metabolism and platelets. By critically analysing existing literature on platelets, the gut microbiome, and stress-linked disorders, we hope to elicit the role of platelets in mediating the effects on serotonin (5-HT) levels and neuroinflammation. We have included studies specifically investigating platelets and TRP metabolism in relation to inflammation, neuroinflammation and neuropsychiatric disorders. Alteration in microbial composition due to stress could contribute to increased intestinal permeability, facilitating the translocation of microbial products, and triggering the release of pro-inflammatory cytokines. This causes platelets to become hyperactive and secrete 5-HT into the plasma. Increased levels of pro-inflammatory cytokines may also lead to increased permeability of the blood-brain barrier (BBB), allowing inflammatory mediators entry into the brain, affecting the balance of TRP metabolism products, such as 5-HT, kynurenic acid (KYNA), and quinolinic acid (QUIN). These alterations may contribute to neuroinflammation and possible neurological damage. Furthermore, platelets can cross the compromised BBB and interact with astrocytes and neurons, leading to the secretion of 5-HT and pro-inflammatory factors, exacerbating inflammatory conditions in the brain. The mechanisms underlying neuroinflammation resulting from peripheral inflammation are still unclear, but the connection between the brain and gut through the bloodstream could be significant. Identifying peripheral biomarkers and mechanisms in the plasma that reflect neuroinflammation may be important. This review serves as a foundation for further research on the association between the gut microbiome, blood microbiome, and neuropsychiatric disorders. The integration of these findings with protein and metabolite markers in the blood may expand our understanding of the subject. [Abstract copyright: Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

Dataset on stroke infarct volume in rodents: A comparison of MRI and histological methods

This dataset offers images of mouse brains impacted by photothrombotic stroke in the sensorimotor cortex published by Weber et al. NeuroImage (2024). Data is gathered using two primary techniques: (1) whole-brain ex-vivo magnetic resonance imaging (MRI) and (2) 40 µm thick coronal histological sections that undergo immunofluorescence staining with NeuroTrace. Infarct areas and volumes are assessed through MRI at two distinct time frames—three days (acute) and 28 days (chronic) following photothrombotic stroke induction. Subsequently, the brains are sectioned into 40 µm thick coronal slices, stained with NeuroTrace, and imaged as whole sections. The dataset holds considerable value for reuse, particularly for researchers focused on stroke volume estimation methods as well as those interested in comparing the efficacy of MRI and histological techniques.ISSN:2352-340

Widespread microbial utilization of ribosomal β-amino acid-containing peptides and proteins

β-Amino residues are regarded as extremely rare features among ribosomal products. They can be installed by a remarkable non-canonical enzymatic splicing process occurring in some Nif11-type ribosomally synthesized and posttranslationally modified peptide (RiPP) pathways from select cyanobacteria. The functions of the final pathway products remained unknown. Here, a global bioinformatic analysis suggested an unexpectedly broad distribution of ribosomal β-amino acid products in diverse bacterial lineages as well as archaea. Characterization of 27 bacterial splicease-substrate pairs confirmed the modification in all cases. The “spliceotide” products include many previously unrecognized RiPP types as well as proteins, contain 35 to >600 residues, and feature single to multiple α-keto-β-amino acid moieties, with 15 different naturally occurring β units characterized and 20 predicted. Of three tested spliceotides, all exhibited exceptionally potent protease inhibitory activity, providing a potential rationale for the widespread splicease chemistry in prokaryotes and highlighting substantial potential for drug discovery and gene-based biomolecule diversification.ISSN:2451-9294ISSN:2451-930