Explore the vast range of titles available.

The genetic and molecular basis of flagellar motility has been investigated for several decades, with innovative research strategies propelling advances at a steady pace. Furthermore, as the phenomenon is examined in diverse bacteria, new taxon-specific regulatory and structural features are being elucidated. Motility is also a straightforward bacterial phenotype that can allow undergraduate researchers to explore the palette of molecular genetic tools available to microbiologists. This study, driven primarily by undergraduate researchers, evaluated hundreds of flagellar motility mutants in the Gram-negative plant-associated bacterium Agrobacterium fabrum. The nearly saturating screen implicates a total of 37 genes in flagellar biosynthesis, including genes of previously unknown function.

Compartments 1 in food webs are subgroups of taxa in which many strong interactions occur within the subgroups and few weak interactions occur between the subgroups 2 . Theoretically, compartments increase the stability in networks 1 , 2 , 3 , 4 , 5 , such as food webs. Compartments have been difficult to detect in empirical food webs because of incompatible approaches 6 , 7 , 8 , 9 or insufficient methodological rigour 8 , 10 , 11 . Here we show that a method for detecting compartments from the social networking science 12 , 13 , 14 identified significant compartments in three of five complex, empirical food webs. Detection of compartments was influenced by food web resolution, such as interactions with weights. Because the method identifies compartmental boundaries in which interactions are concentrated, it is compatible with the definition of compartments. The method is rigorous because it maximizes an explicit function, identifies the number of non-overlapping compartments, assigns membership to compartments, and tests the statistical significance of the results 12 , 13 , 14 . A graphical presentation 14 reveals systemic relationships and taxa-specific positions as structured by compartments. From this graphic, we explore two scenarios of disturbance to develop a hypothesis for testing how compartmentalized interactions increase stability in food webs 15 , 16 , 17 .

Research into mechanisms of skin scarring identified transforming growth factor β3 (TGFβ3) as a potential antiscarring therapy. We assessed scar improvement with avotermin (recombinant, active, human TGFβ3). In three double-blind, placebo-controlled studies, intradermal avotermin (concentrations ranging from 0·25 to 500 ng/100 μL per linear cm wound margin) was administered to both margins of 1 cm, full-thickness skin incisions, before wounding and 24 h later, in healthy men and women. Treatments (avotermin and placebo or standard wound care) were randomly allocated to wound sites by a computer generated randomisation scheme, and within-participant controls compared avotermin versus placebo or standard wound care alone. Primary endpoints were visual assessment of scar formation at 6 months and 12 months after wounding in two studies, and from week 6 to month 7 after wounding in the third. Investigators, participants, and scar assessors were blinded to treatment. Efficacy analyses were intention to treat. These studies are registered with ClinicalTrials.gov, numbers NCT00847925, NCT00847795, and NCT00629811. In two studies, avotermin 50 ng/100 μL per linear cm significantly improved median score on a 100 mm visual analogue scale (VAS) by 5 mm (range −2 to 14; p=0·001) at month 6 and 8 mm (−29 to 18; p=0·0230) at month 12. In the third, avotermin significantly improved total scar scores at all concentrations versus placebo (mean improvement: from 14·84 mm [95 % CI 5·5–24·2] at 5 ng/100 μL per linear cm to 64·25 mm [49·4–79·1] at 500 ng/100 μL per linear cm). Nine [60%] scars treated with avotermin 50 ng/100 μL per linear cm showed 25% or less abnormal orientation of collagen fibres in the reticular dermis versus five [33%] placebo scars. After only 6 weeks from wounding, avotermin 500 ng/100 μL per linear cm improved VAS score by 16·12 mm (95% CI 10·61–21·63). Adverse events at wound sites were similar for avotermin and controls. Erythema and oedema were more frequent with avotermin than with placebo, but were transient and deemed to be consistent with normal wound healing. Avotermin has potential to provide an accelerated and permanent improvement in scarring. Renovo (UK).

A number of new measurement methods for ice nucleating particles (INPs) have been introduced in recent years, and it is important to address how these methods compare. Laboratory comparisons of instruments sampling major INP types are common, but few comparisons have occurred for ambient aerosol measurements exploring the utility, consistency and complementarity of different methods to cover the large dynamic range of INP concentrations that exists in the atmosphere. In this study, we assess the comparability of four offline immersion freezing measurement methods (Colorado State University ice spectrometer, IS; North Carolina State University cold stage, CS; National Institute for Polar Research Cryogenic Refrigerator Applied to Freezing Test, CRAFT; University of British Columbia micro-orifice uniform deposit impactor–droplet freezing technique, MOUDI-DFT) and an online method (continuous flow diffusion chamber, CFDC) used in a manner deemed to promote/maximize immersion freezing, for the detection of INPs in ambient aerosols at different locations and in different sampling scenarios. We also investigated the comparability of different aerosol collection methods used with offline immersion freezing instruments. Excellent agreement between all methods could be obtained for several cases of co-sampling with perfect temporal overlap. Even for sampling periods that were not fully equivalent, the deviations between atmospheric INP number concentrations measured with different methods were mostly less than 1 order of magnitude. In some cases, however, the deviations were larger and not explicable without sampling and measurement artifacts. Overall, the immersion freezing methods seem to effectively capture INPs that activate as single particles in the modestly supercooled temperature regime (> −20 °C), although more comparisons are needed in this temperature regime that is difficult to access with online methods. Relative to the CFDC method, three immersion freezing methods that disperse particles into a bulk liquid (IS, CS, CRAFT) exhibit a positive bias in measured INP number concentrations below −20 °C, increasing with decreasing temperature. This bias was present but much less pronounced for a method that condenses separate water droplets onto limited numbers of particles prior to cooling and freezing (MOUDI-DFT). Potential reasons for the observed differences are discussed, and further investigations proposed to elucidate the role of all factors involved.

In this trial of simvastatin involving critically ill patients with Covid-19, which was stopped owing to reduced cases, simvastatin did not meet the prespecified criteria for superiority to control treatment.

Anhedonic depression is a subtype of depression characterized by deficits in reward processing. This subtype of depression is associated with higher suicide risk and longer depressive episodes, underscoring the importance of effective treatments. Anhedonia has also been found to correlate with alterations in activity in several subcortical regions, including the caudate head and nucleus accumbens. Low intensity focused ultrasound pulsation (LIFUP) is an emerging technology that enables non-invasive stimulation of these subcortical regions, which were previously only accessible with surgically-implanted electrodes. This double-blinded, sham-controlled study aims to investigate the effects of LIFUP to the left caudate head and right nucleus accumbens in participants with anhedonic depression. Participants in this protocol will undergo three sessions of LIFUP over the span of 5-9 days. To investigate LIFUP-related changes, this 7-week protocol collects continuous digital phenotyping data, an array of self-report measures of depression, anhedonia, and other psychopathology, and magnetic resonance imaging (MRI) before and after the LIFUP intervention. Primary self-report outcome measures include Ecological Momentary Assessment, the Positive Valence Systems Scale, and the Patient Health Questionnaire. Primary imaging measures include magnetic resonance spectroscopy and functional MRI during reward-based tasks and at rest. Digital phenotyping data is collected with an Apple Watch and participants' personal iPhones throughout the study, and includes information about sleep, heart rate, and physical activity. This study is the first to investigate the effects of LIFUP to the caudate head or nucleus accumbens in depressed subjects. Furthermore, the data collected for this protocol covers a wide array of potentially affected modalities. As a result, this protocol will help to elucidate potential impacts of LIFUP in individuals with anhedonic depression.

Background Salt marshes are major natural repositories of sequestered organic carbon with high burial rates of organic matter, produced by highly productive native flora. Accumulated carbon predominantly exists as lignocellulose which is metabolised by communities of functionally diverse microbes. However, the organisms that orchestrate this process and the enzymatic mechanisms employed that regulate the accumulation, composition and permanence of this carbon stock are not yet known. We applied meta-exo-proteome proteomics and 16S rRNA gene profiling to study lignocellulose decomposition in situ within the surface level sediments of a natural established UK salt marsh. Results Our studies revealed a community dominated by Gammaproteobacteria , Bacteroidetes and Deltaproteobacteria that drive lignocellulose degradation in the salt marsh. We identify 42 families of lignocellulolytic bacteria of which the most active secretors of carbohydrate-active enzymes were observed to be Prolixibacteracea , Flavobacteriaceae , Cellvibrionaceae , Saccharospirillaceae , Alteromonadaceae , Vibrionaceae and Cytophagaceae . These families secreted lignocellulose-active glycoside hydrolase (GH) family enzymes GH3, GH5, GH6, GH9, GH10, GH11, GH13 and GH43 that were associated with degrading Spartina biomass. While fungi were present, we did not detect a lignocellulolytic contribution from fungi which are major contributors to terrestrial lignocellulose deconstruction. Oxidative enzymes such as laccases, peroxidases and lytic polysaccharide monooxygenases that are important for lignocellulose degradation in the terrestrial environment were present but not abundant, while a notable abundance of putative esterases (such as carbohydrate esterase family 1) associated with decoupling lignin from polysaccharides in lignocellulose was observed. Conclusions Here, we identify a diverse cohort of previously undefined bacteria that drive lignocellulose degradation in the surface sediments of the salt marsh environment and describe the enzymatic mechanisms they employ to facilitate this process. Our results increase the understanding of the microbial and molecular mechanisms that underpin carbon sequestration from lignocellulose within salt marsh surface sediments in situ and provide insights into the potential enzymatic mechanisms regulating the enrichment of polyphenolics in salt marsh sediments. 2Bi9cdUnFhfykPyYYU2FLj Video Abstract

For most classes of drugs, rapid development of therapeutics to treat emerging infections is challenged by the timelines needed to identify compounds with the desired efficacy, safety, and pharmacokinetic profiles. Fully human monoclonal antibodies (mAbs) provide an attractive method to overcome many of these hurdles to rapidly produce therapeutics for emerging diseases. In this study, we deployed a platform to generate, test, and develop fully human antibodies to Zaire ebolavirus. We obtained specific anti-Ebola virus (EBOV) antibodies by immunizing VelocImmune mice that use human immunoglobulin variable regions in their humoral responses. Of the antibody clones isolated, 3 were selected as best at neutralizing EBOV and triggering FcγRIIIa. Binding studies and negative-stain electron microscopy revealed that the 3 selected antibodies bind to non-overlapping epitopes, including a potentially new protective epitope not targeted by other antibody-based treatments. When combined, a single dose of a cocktail of the 3 antibodies protected nonhuman primates (NHPs) from EBOV disease even after disease symptoms were apparent. This antibody cocktail provides complementary mechanisms of actions, incorporates novel specificities, and demonstrates high-level postexposure protection from lethal EBOV disease in NHPs. It is now undergoing testing in normal healthy volunteers in preparation for potential use in future Ebola epidemics.

Human space exploration poses inherent risks to astronauts’ health, leading to molecular changes that can significantly impact their well-being. These alterations encompass genomic instability, mitochondrial dysfunction, increased inflammation, homeostatic dysregulation, and various epigenomic changes. Remarkably, these changes bear similarities to those observed during the aging process on Earth. However, our understanding of the connection between these molecular shifts and disease development in space remains limited. Frailty syndrome, a clinical syndrome associated with biological aging, has not been comprehensively investigated during spaceflight. To bridge this knowledge gap, we leveraged murine data obtained from NASA’s GeneLab, along with astronaut data gathered from the JAXA and Inspiration4 missions. Our objective was to assess the presence of biological markers and pathways related to frailty, aging, and sarcopenia within the spaceflight context. Through our analysis, we identified notable changes in gene expression patterns that may be indicative of the development of a frailty-like condition during space missions. These findings suggest that the parallels between spaceflight and the aging process may extend to encompass frailty as well. Consequently, further investigations exploring the utility of a frailty index in monitoring astronaut health appear to be warranted.

Background UK national clinical guidance recommends that men with prostate cancer on androgen deprivation therapy are offered twice weekly supervised aerobic and resistance exercise to address iatrogenic harm caused by treatment. Very few NHS trusts have established adequate provision of such services. Furthermore, interventions fail to demonstrate sustained behaviour change. The STAMINA lifestyle intervention offers a system-level change to clinical care delivery addressing barriers to long-term behaviour change and implementation of new prostate cancer care pathways. This trial aims to establish whether STAMINA is clinically and cost-effective in improving cancer-specific quality of life and/or reducing fatigue compared to optimised usual care. The process evaluation aims to inform the interpretation of results and, if the intervention is shown to benefit patients, to inform the implementation of the intervention into the NHS. Methods Men with prostate cancer on androgen deprivation therapy ( n  = 697) will be identified from a minimum of 12 UK NHS trusts to participate in a multi-centre, two-arm, individually randomised controlled trial. Consenting men will have a ‘safety to exercise’ check and be randomly allocated (5:4) to the STAMINA lifestyle intervention ( n  = 384) or optimised usual care ( n  = 313). Outcomes will be collected at baseline, 3-, 6- and 12-month post-randomisation. The two primary outcomes are cancer-specific quality of life and fatigue. The parallel process evaluation will follow a mixed-methods approach to explore recruitment and aspects of the intervention including, reach, fidelity, acceptability, and implementation. An economic evaluation will estimate the cost-effectiveness of the STAMINA lifestyle intervention versus optimised usual care and a discrete choice experiment will explore patient preferences. Discussion The STAMINA lifestyle intervention has the potential to improve quality of life and reduce fatigue in men on androgen deprivation therapy for prostate cancer. Embedding supervised exercise into prostate cancer care may also support long-term positive behaviour change and reduce adverse events caused by treatment. Findings will inform future clinical care and could provide a blueprint for the integration of supervised exercise and behavioural support into other cancer and/or clinical services. Trial registration ISRCTN 46385239, registered on 30/07/2020. Cancer Research UK 17002, retrospectively registered on 24/08/2022.