Impact of mindfulness training and yoga on injury and pain-related impairment: a group randomized trial in basic combat training.

Introduction: Service members are at risk for pain-related difficulties in functioning and physical injury. Previous studies suggest that mindfulness training (MT) and yoga may prevent these outcomes. The present study was designed to determine the impact of MT and yoga on the health, pain, and injury of Army trainees completing 10 weeks of basic combat training (BCT). Methods: Platoons (≈40 trainees per platoon) were randomized to MT and yoga or training-as-usual in October to December 2020 at a large installation in the US. Self-reported outcomes were health, pain level, and pain impact on training, sleep, mood, and stress. Objective outcomes were injury-related medical encounters and number of diagnoses. The trial was registered at ClinicalTrials. Gov (NCT05550610). Results: Intervention trainees reported significantly better health (OR = 1.05, 95% CI [1.00, 1.10]) and less impact of pain on training (OR = 0.81, 95% CI [0.74, 0.90]), sleep (OR = 0.88, 95% CI [0.81, 0.95]), mood (OR = 0.86, 95% CI [0.78, 0.96]), and stress (OR = 0.88, 95% CI [0.79, 0.98]). There was no significant difference in injury-related medical encounters (AOR = 0.70, 95% CI [0.48, 1.03]), but intervention trainees had fewer diagnoses (OR = 0.67, 95% CI [0.47, 0.95]) and were 30% less likely to have a first medical encounter at any time during BCT. This difference emerged 3 weeks into BCT. Discussion: A combined MT and yoga intervention resulted in better trainee health. The US Army and other organizations requiring resilience under extreme stress should consider implementing MT and yoga to offset risks to employee health.

High-resolution app data reveal sustained increases in recreational fishing effort in Europe during and after COVID-19 lockdowns.

It is well recognized that COVID-19 lockdowns impacted human interactions with natural ecosystems. One example is recreational fishing, which, in developed countries, involves approximately 10% of people. Fishing licence sales and observations at angling locations suggest that recreational fishing effort increased substantially during lockdowns. However, the extent and duration of this increase remain largely unknown. We used four years (2018-2021) of high-resolution data from a personal fish-finder device to explore the impact of COVID-19 lockdowns on angling effort in four European countries. We show that relative device use and angling effort increased 1.2-3.8-fold during March-May 2020 and generally remained elevated even at the end of 2021. Fishing during the first lockdown also became more frequent on weekdays. Statistical models explained 50-70% of the variation, suggesting that device use and angling effort were relatively consistent and predictable through space and time. Our study demonstrates that recreational fishing behaviour can change substantially and rapidly in response to societal shifts, with profound ecological, human well-being and economic implications. We also show the potential of angler devices and smartphone applications for high-resolution fishing effort analysis and encourage more extensive science and industry collaborations to take advantage of this information.

Alternative signal pathways underly fertilization and egg activation in a fish with contrasting modes of spawning.

BACKGROUND: The processes of fertilization and egg activation are vital for early embryogenesis. However, while the mechanisms associated with key events during these processes differ among species and modes of spawning, the signal pathways underlying these processes are opaque for many fishes, including economically important species. RESULTS: We investigated phenotypic traits, ultrastructure and protein expression levels in the eggs of the topmouth culter (Culter alburnus), a protected and economically important freshwater fish that exhibits two spawning modes, producing semi-buoyant eggs and adhesive eggs. Unfertilized eggs of C. alburnus were examined, as well as eggs at fertilization and 30 min post fertilization. Our results showed that in semi-buoyant eggs, energy metabolism was activated at fertilization, followed by elevated protein expression of cytoskeleton and extracellular matrix (ECM)-receptor interactions that resulted in rapid egg swelling; a recognized adaptation for lotic habitats. In contrast, in adhesive eggs fertilization initiated the process of sperm-egg fusion and blocking of polyspermy, followed by enhanced protein expression of lipid metabolism and the formation of egg envelope adhesion and hardening, which are adaptive in lentic habitats. CONCLUSION: Our findings indicate that alternative signal pathways differ between modes of spawning and timing during the key processes of fertilization and egg activation, providing new insights into the molecular mechanisms involved in adaptive early embryonic development in teleost fishes.

Talking Trials: An arts-based exploration of attitudes to clinical trials amongst minority ethnic members of the South Riverside Community of Cardiff.

INTRODUCTION: Clinical trials must include diverse participants to ensure the wide applicability of results. However, people from ethnic minorities are included in clinical trials at rates lower than expected given their share of the population. Working with South Riverside Community Development Centre (SRCDC), Talking Trials used public engagement to foster discussions around the underrepresentation of those from minority ethnic communities in clinical trials and to identify and address concerns surrounding trial participation. METHODS: We conducted three workshops with 13 co-researchers from minority ethnic backgrounds. We explored perceptions and understanding of clinical trials alongside participatory art activities to help move away from verbocentric methods of communication. These artworks formed an exhibition that was presented to the community, prompting further discussions and engagement. FINDINGS: Co-production workshops were an effective tool to introduce the public to trial research. With little knowledge of clinical trials at the beginning of the process, our co-researchers formed a cohesive group, sharing initial fears and mistrust towards trials. As conversations progressed these attitudes clearly shifted. Artwork produced during the workshops was incorporated into an exhibition. Quotes and creative pieces from the group were included to reflect the themes identified. Presenting the exhibition at Riverside Festival enabled further engagement with a wider diverse community. The focus on co-production helped build a network of individuals new to research and keen to become involved further. CONCLUSION: Inclusive and democratic co-production, enriched by participatory art practices, provided a powerful means of enabling our group to create new insights and foster new relationships. Projects like Talking Trials can diversify the research process itself-for example, four co-researchers have commenced lay research partner roles on trial management groups and a lay advisory group is in development. PATIENT OR PUBLIC CONTRIBUTION: Three members of staff at SRCDC were on the project delivery group and involved in the initial project design, subsequently helping to connect us with members of the Riverside community to work as co-researchers. Two of the SRCDC staff are co-authors of this manuscript. The project had 13 public co-researchers guiding the direction of this research and creating the artwork displayed in the art exhibition.

An evolutionarily conserved pacemaker role for HCN ion channels in smooth muscle.

Although hyperpolarization-activated cation (HCN) ion channels are well established to underlie cardiac pacemaker activity, their role in smooth muscle organs remains controversial. HCN-expressing cells are localized to renal pelvic smooth muscle (RPSM) pacemaker tissues of the murine upper urinary tract and HCN channel conductance is required for peristalsis. To date, however, the Ih pacemaker current conducted by HCN channels has never been detected in these cells, raising questions on the identity of RPSM pacemakers. Indeed, the RPSM pacemaker mechanisms of the unique multicalyceal upper urinary tract exhibited by humans remains unknown. Here, we developed immunopanning purification protocols and demonstrate that 96% of isolated HCN+ cells exhibit Ih . Single-molecule STORM to whole-tissue imaging showed HCN+ cells express single HCN channels on their plasma membrane and integrate into the muscular syncytium. By contrast, PDGFR-α+ cells exhibiting the morphology of ICC gut pacemakers were shown to be vascular mural cells. Translational studies in the homologous human and porcine multicalyceal upper urinary tracts showed that contractions and pacemaker depolarizations originate in proximal calyceal RPSM. Critically, HCN+ cells were shown to integrate into calyceal RPSM pacemaker tissues, and HCN channel block abolished electrical pacemaker activity and peristalsis of the multicalyceal upper urinary tract. Cumulatively, these studies demonstrate that HCN ion channels play a broad, evolutionarily conserved pacemaker role in both cardiac and smooth muscle organs and have implications for channelopathies as putative aetiologies of smooth muscle disorders. KEY POINTS: Pacemakers trigger contractions of involuntary muscles. Hyperpolarization-activated cation (HCN) ion channels underpin cardiac pacemaker activity, but their role in smooth muscle organs remains controversial. Renal pelvic smooth muscle (RPSM) pacemakers trigger contractions that propel waste away from the kidney. HCN+ cells localize to murine RPSM pacemaker tissue and HCN channel conductance is required for peristalsis. The HCN (Ih ) current has never been detected in RPSM cells, raising doubt whether HCN+ cells are bona fide pacemakers. Moreover, the pacemaker mechanisms of the unique multicalyceal RPSM of higher order mammals remains unknown. In total, 97% of purified HCN+ RPSM cells exhibit Ih . HCN+ cells integrate into the RPSM musculature, and pacemaker tissue peristalsis is dependent on HCN channels. Translational studies in human and swine demonstrate HCN channels are conserved in the multicalyceal RPSM and that HCN channels underlie pacemaker activity that drives peristalsis. These studies provide insight into putative channelopathies that can underlie smooth muscle dysfunction.

Short-term neurochemical effects of transcutaneous trigeminal nerve stimulation using 7T magnetic resonance spectroscopy.

BACKGROUND AND PURPOSE: The purpose was to explore the effects of transcutaneous trigeminal nerve stimulation (TNS) on neurochemical concentrations (brainstem, anterior cingulate cortex [ACC], dorsolateral prefrontal cortex [DLPFC], ventromedial prefrontal cortex [VMPFC], and the posterior cingulate cortex [PCC]) using ultrahigh-field magnetic resonance spectroscopy. METHODS: This double-blinded study tested 32 healthy males (age: 25.4 ± 7.3 years) on two separate occasions where participants received either a 20-minute TNS or sham session. Participants were scanned at baseline and twice post-TNS/sham administration. RESULTS: There were no group differences in concentration changes of glutamate, gamma-aminobutyric acid, glutamine, myoinositol (mI), total N-acetylaspartate, total creatine (tCr), and total choline between the baseline scan and the first post-TNS/sham scan and between the first and second post-TNS/sham scan in the brainstem, ACC, DLPFC, VMPFC, and PCC. Between the baseline scan and the second post-TNS/sham scan, changes in tCr (mean difference = 0.280 mM [0.075 to 0.485], p = .026) and mI (mean difference = 0.662 mM [0.203 to 1.122], p = .026) in the DLPFC differed between groups. Post hoc analyses indicated that there was a decrease in tCr (mean change = -0.201 mM [-0.335 to -0.067], p = .003) and no change in mI (mean change = -0.327 mM [-0.737 to 0.083], p = .118) in the TNS group; conversely, there was no change in tCr (mean change = -0.100 mM [-0.074 to 0.274], p = .259) and an increase in mI (mean change = 0.347 mM [0.106 to 0.588], p = .005) in the sham group. CONCLUSION: These data demonstrate that a single session of unilateral TNS slightly decreased tCr concentrations in the DLPFC region.

Three Adult Cases of STAT1 Gain-of-Function with Chronic Mucocutaneous Candidiasis Treated with JAK Inhibitors.

PURPOSE: The aim of this study was to characterize clinical effects and biomarkers in three patients with chronic mucocutaneous candidiasis (CMC) caused by gain-of-function (GOF) mutations in the STAT1 gene during treatment with Janus kinase (JAK) inhibitors. METHODS: Mass cytometry (CyTOF) was used to characterize mononuclear leukocyte populations and Olink assay to quantify 265 plasma proteins. Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA) was used to quantify the reactivity against Candida albicans. RESULTS: Overall, JAK inhibitors improved clinical symptoms of CMC, but caused side effects in two patients. Absolute numbers of neutrophils, T cells, B cells, and NK cells were sustained during baricitinib treatment. Detailed analysis of cellular subsets, using CyTOF, revealed increased expression of CD45, CD52, and CD99 in NK cells, reflecting a more functional phenotype. Conversely, monocytes and eosinophils downregulated CD16, consistent with reduced inflammation. Moreover, T and B cells showed increased expression of activation markers during treatment. In one patient with a remarkable clinical effect of baricitinib treatment, the immune response to C. albicans increased after 7 weeks of treatment. Alterations in plasma biomarkers involved downregulation of cellular markers CXCL10, annexin A1, granzyme B, granzyme H, and oncostatin M, whereas FGF21 was the only upregulated marker after 7 weeks. After 3 months, IFN-É£ and CXCL10 were downregulated. CONCLUSIONS: The clinical effect of JAK inhibitor treatment of CMC is promising. Several biological variables were altered during baricitinib treatment demonstrating that lymphocytes, NK cells, monocytes, and eosinophils were affected. In parallel, cellular reactivity against C. albicans was enhanced.

Molecular Mechanisms of Spawning Habits for the Adaptive Radiation of Endemic East Asian Cyprinid Fishes.

Despite the widespread recognition of adaptive radiation as a driver of speciation, the mechanisms by which natural selection generates new species are incompletely understood. The evolutionary radiation of endemic East Asian cyprinids has been proposed as evolving through a change in spawning habits, involving a transition from semibuoyant eggs to adhesive eggs in response to crosslinked river-lake system formation. Here, we investigated the molecular mechanisms that underpin this radiation, associated with egg hydration and adhesiveness. We demonstrated that semibuoyant eggs enhance hydration by increasing the degradation of yolk protein and accumulation of Ca2+ and Mg2+ ions, while adhesive eggs improve adhesiveness and hardness of the egg envelope by producing an adhesive layer and a unique 4th layer to the egg envelope. Based on multiomics analyses and verification tests, we showed that during the process of adaptive radiation, adhesive eggs downregulated the "vitellogenin degradation pathway," "zinc metalloprotease pathway," and "ubiquitin-proteasome pathway" and the pathways of Ca2+ and Mg2+ active transport to reduce their hydration. At the same time, adhesive eggs upregulated the crosslinks of microfilament-associated proteins and adhesive-related proteins, the hardening-related proteins of the egg envelope, and the biosynthesis of glycosaminoglycan in the ovary to generate adhesiveness. These findings illustrate the novel molecular mechanisms associated with hydration and adhesiveness of freshwater fish eggs and identify critical molecular mechanisms involved in the adaptive radiation of endemic East Asian cyprinids. We propose that these key egg attributes may function as "magic traits" in this adaptive radiation.

Spatial heterogeneity in pH, body size and habitat size generates ecological opportunity in an evolutionary radiation.

Much of the biological diversity we see today is thought to be the product of evolutionary radiation, the rapid proliferation of species from a single ancestor into multiple discrete forms. Spatial heterogeneity in environmental variables has been proposed as creating the necessary ecological opportunity to stimulate evolutionary radiation. Nonetheless, the ecological mechanisms generating and maintaining diversity in spatially heterogeneous environments are not fully understood. The authors investigated the role of strong spatial heterogeneity in generating ecological opportunity in an evolutionary radiation of freshwater populations of the three-spined stickleback (Gasterosteus aculeatus L.) on the island of North Uist using a spatially explicit Bayesian model. The authors identified pH, loch surface area and body size as predictors of variance in the number of lateral plates that comprise anti-predator armour in G. aculeatus. An East-West gradient of pH, a product of the distinctive environment of North Uist, generates a robust selective environment facilitating G. aculeatus evolutionary radiation. Larger lochs were associated with atypical phenotypes, possibly related to larger population sizes and greater selection efficiency. An association between pH and lateral plate number is likely an effect of body size, with a positive relationship between body size and lateral plate number that is mediated by swimming efficiency in G. aculeatus.

Do reduced numbers of plasmacytoid dendritic cells contribute to the aggressive clinical course of COVID-19 in chronic lymphocytic leukaemia?

Infections with SARS-CoV-2 have been unduly severe in patients with haematological malignancies, in particular in those with chronic lymphocytic leukaemia (CLL). Based on a series of observations, we propose that an underlying mechanism for the aggressive clinical course of COVID-19 in CLL is a paucity of plasmacytoid dendritic cells (pDCs) in these patients. Indeed, pDCs express Toll-like receptor 7 (TLR7), which together with interferon-regulatory factor 7 (IRF7), enables pDCs to produce large amounts of type I interferons, essential for combating COVID-19. Treatment of CLL with Bruton's tyrosine kinase (BTK) inhibitors increased the number of pDCs, likely secondarily to the reduction in the tumour burden.

Supplemental Protein and a Multinutrient Beverage Speed Wound Healing after Acute Sleep Restriction in Healthy Adults.

BACKGROUND: Physiologic and psychologic stress slow healing from experimental wounds by impairing immune function. OBJECTIVES: We aimed to determine whether supplemental protein and multinutrient supplementation improved wound healing markers after acute stress induced by acute sleep restriction. METHODS: In this single-blind, crossover study in generally healthy young adults (18 males/2 females; mean ± SD age: 19.7 ± 2.30 y), experimental wounds were created by removing the top layer of forearm blisters induced via suction after 48 h of 72-h sleep restriction (2-h nightly sleep), a protocol previously shown to delay wound healing. Skin barrier restoration (measured by transepidermal water loss) assessed wound healing ≤10 d postblistering, and local immune responses were evaluated by serial measurement of cytokine concentrations in fluid collected at wound sites for 48 h postblistering. Participants consumed controlled, isocaloric diets with either 0.900 g · kg-1 · d-1 protein plus placebo (PLA) or 1.50 g · kg-1 · d-1 protein plus multinutrient beverage [l-arginine: 20.0 g/d; l-glutamine: 30.0 g/d; omega-3 (n-3) fatty acids: 1.00 g/d; zinc sulfate: 24.0 mg/d; cholecalciferol: 800 IU/d; and vitamin C: 400 mg/d] (NUT) during sleep restriction and for 4 d afterwards. RESULTS: Skin barrier restoration (primary outcome) was shorter for NUT (median: 3.98 d; IQR: 1.17 d) than for PLA (median: 5.25 d; IQR: 1.05 d) (P = 0.001). Cytokines from wound fluid (secondary outcome) increased over time (main effect of time P ≤ 0.001), except IL-13 (P = 0.07); however, no effects of treatment were observed. CONCLUSIONS: Supplemental nutrition may promote wound healing after sleep restriction in healthy adults including military personnel, the latter of which also have a high incidence of wounds and infection.This trial was registered at clinicaltrials.gov as NCT03525184.

Genetic diversification of the Kanehira bitterling Acheilognathus rhombeus inferred from mitochondrial DNA, with comments on the phylogenetic relationship with its sister species Acheilognathus barbatulus.

The Kanehira bitterling, Acheilognathus rhombeus, is a freshwater fish, discontinuously distributed in western Japan and the Korean Peninsula. Unusually among bitterling it is an autumn-spawning species and shows developmental diapause. Consequently, the characterization of its evolutionary history is significant not only in the context of the fish assemblage of East Asia, but also for understanding life-history evolution. This study aimed to investigate the phylogeography of A. rhombeus and its sister species Acheilognathus barbatulus, distributed in China, using a mitochondrial analysis of the ND1 gene from 311 samples collected from 50 localities in Japan and continental Asia. Phylogenetic analysis revealed that A. barbatulus is included in A. rhombeus and genetically closer to Japanese A. rhombeus than to Korean A. rhombeus. Divergence of Korean A. rhombeus and A. barbatulus from Japanese A. rhombeus was estimated to be from the late Pliocene (3.44 Mya) and the early Pleistocene (1.98 Mya), respectively. Each event closely coincided with the time of the Japan Sea opening. Japanese A. rhombeus comprised seven lineages: three in Honshu and four in Kyushu. One lineage in central Kyushu was genetically closer to the Honshu lineages than to other lineages in northern Kyushu. Divergence of Japanese lineages was estimated to be from the early to middle Pleistocene (0.55-0.93 Mya), during a period of geological and paleoclimatic change, including volcanic activity. Population expansion in the late Pleistocene (<0.10 Ma) was suggested in many of the lineages, which accords with other freshwater fishes. Biogeographically the ancestral A. rhombeus/A. barbatulus was likely to have repeatedly colonized Japan from the continent through land bridges in the late Pliocene and the early Pleistocene. However, the close genetic relationship between Japanese A. rhombeus and A. barbatulus suggests another possibility, with the second colonization occurring in reverse, from Japan to China. The small genetic distance between them indicates that the colonization occurred later than colonization events of other freshwater fishes, including other bitterling species.

Distribution patterns of epiphytic reed-associated macroinvertebrate communities across European shallow lakes.

So far, research on plant-associated macroinvertebrates, even if conducted on a large number of water bodies, has mostly focused on a relatively small area, permitting limited conclusions to be drawn regarding potentially broader geographic effects, including climate. Some recent studies have shown that the composition of epiphytic communities may differ considerably among climatic zones. To assess this phenomenon, we studied macroinvertebrates associated with the common reed Phragmites australis (Cav.) Trin. ex Steud in 46 shallow lakes using a common protocol. The lakes, located in nine countries, covered almost the entire European latitudinal range (from <48°N to 61°N) and captured much of the variability in lake size and nutrient content in the region. A Poisson Generalized Linear Mixed Model (GLMM) showed the number of macroinvertebrate epiphytic taxa to be negatively associated with water conductivity and positively associated with medium ice cover duration (approximately 1 month). A Gamma GLMM showed a positive effect of chlorophyll a on the density of macroinvertebrates, and a significantly greater density in lakes located at the lowest and highest latitudes. Individual taxa responded differently to lake environmental conditions across climate zones. Chironomidae dominated in all climate zones, but their contribution to total density decreased with increasing latitude, with progressively greater proportions of Naidinae, Asellidae, Ephemeroptera and Trichoptera. Our study demonstrates that epiphytic macroinvertebrate fauna, even when analyzed at low taxonomic resolution, exhibits clear differences in diversity, relative abundance of individual taxa and total density, shaped both by geographic and anthropogenic variables. The results were discussed in the context of climate change. To our best knowledge this is the first study to examine epiphytic fauna carried out on a European scale.

Vehicular tracks and the influence of land use and habitat protection in the British uplands.

Uplands cover around 25% of the Earth's land surface and comprise highly sensitive soils and habitats of global ecological importance that together provision a suite of valuable ecosystem services. Access to upland areas for land management and recreation is increasingly dependent on the use of motorised vehicles. However, despite the widely acknowledged detrimental consequences of vehicle track development and use, this activity is not currently quantified or monitored. In this study, surfaced and unsurfaced vehicular tracks, footpaths and land cover in an approximately 5% sample of mainland British uplands (1910 km2) were mapped using aerial imagery dating between 2007 and 2016. An information theory approach was used to identify models that best predicted the presence and extent of surfaced tracks as a function of land cover, protected status, extent of blanket peat, proximity to human population and altitude. A total of 2104 km of track were recorded, with 27% defined as being surfaced. This equates to a mean (±SE) track density of 1.10 ± 0.15 km km-2 in current use by vehicles across upland Britain. Areas of managed heather and grass-dominated habitat were the primary predictors of the presence and extent of surfaced tracks and we found no evidence that areas of conservation interest with protective designation were less susceptible to track construction. These data indicate that wide-ranging vehicular track networks exist in ecologically sensitive environments across the British uplands, with implications for the integrity of sensitive habitats and soils. Land use and management activities that are not facilitating ecological improvement or conservation appear to be driving the presence of surfaced tracks in 'protected' areas. The findings suggest that: a) urgent review and revision of upland track legislation is required in Great Britain; and b) wider assessment of upland tracks should be undertaken to inform global conservation strategies for these environments.

Geographical variation in the risk of H7N9 human infections in China: implications for risk-based surveillance.

The influenza A (H7N9) subtype remains a public health problem in China affecting individuals in contact with live poultry, particularly at live bird markets. Despite enhanced surveillance and biosecurity at LBMs H7N9 viruses are now more widespread in China. This study aims to quantify the temporal relationship between poultry surveillance results and the onset of human H7N9 infections during 2013-2017 and to estimate risk factors associated with geographical risk of H7N9 human infections in counties in Southeast China. Our results suggest that poultry surveillance data can potentially be used as early warning indicators for human H7N9 notifications. Furthermore, we found that human H7N9 incidence at county-level was significantly associated with the presence of wholesale LBMs, the density of retail LBMs, the presence of poultry virological positives, poultry movements from high-risk areas, as well as chicken population density and human population density. The results of this study can influence the current AI H7N9 control program by supporting the integration of poultry surveillance data with human H7N9 notifications as an early warning of the timing and areas at risk for human infection. The findings also highlight areas in China where monitoring of poultry movement and poultry infections could be prioritized.

Captivity-induced metabolic programming in an endangered felid: implications for species conservation.

Reintroduction of captive-bred individuals into the wild is an important conservation activity. However, environmental conditions can influence developmental programming, potentially causing metabolic disorders in adults. These effects are investigated here for the first time in an endangered species. Using body weight and feed intake data for Iberian lynx (Lynx pardinus) (n = 22), we compared the growth of captive versus wild born and/or reared individuals. Captive-born individuals gained weight as a function of calorie intake, unlike wild-born individuals. When compared with females reared in the wild, captive-reared females achieved a larger body size, without evidence of obesity. Captivity-associated changes to metabolic programming may compromise survival in the wild if an increased body size incurs a greater energy requirement. Large body size may also confer a competitive advantage over smaller, wild-born individuals, disrupting the social organisation of existing wild populations, and inferring long-term implications for the phenotypic composition of wild populations.

Subverting Hedgehog Protein Autoprocessing by Chemical Induction of Paracatalysis.

Hedgehog proteins, a family of vital cell signaling factors, are expressed in precursor form, which requires specialized autoprocessing, called cholesterolysis, for full biological activity. Cholesterolysis occurs in cis through the action of the precursor's C-terminal enzymatic domain, HhC. In this work, we describe HhC activator compounds (HACs), a novel class of noncovalent modulators that induce autoprocessing infidelity, diminishing native cholesterolysis in favor of precursor autoproteolysis, an otherwise minor and apparently nonphysiological side reaction. HAC-induced autoproteolysis generates hedgehog protein that is cholesterol free and hence signaling deficient. The most effective HAC has an AC50 of 9 µM, accelerates HhC autoproteolytic activity by 225-fold, and functions in the presence and absence of cholesterol, the native substrate. HACs join a rare class of "antagonists" that suppress native enzymatic activity by subverting mechanistic fidelity.

The role of detritivory as a feeding tactic in a harsh environment - a case study of weatherfish (Misgurnus fossilis).

The weatherfish (Misgurnus fossilis) is a species that is tolerant of unfavourable environmental conditions and can survive low dissolved oxygen concentrations and high water temperatures. Although this species occurs across almost the whole of Europe, and is protected in many countries, relatively little is known regarding its ecology. To determine the diet of weatherfish, 120 individuals from an artificial drainage canal in central Poland were collected in two seasons (spring and late summer) with contrasting abiotic condition (oxygen concentration, water temperature and transparency). Analysis of gut fullness showed that weatherfish consumed a greater quantity of food in spring (0.92 ± 0.90) compared with summer (0.20 ± 0.26). Contrary to other cobitid taxa, weatherfish fed actively during daytime in both seasons. An estimate of the importance of each dietary component indicated that the most important food categories were chironomids, copepods, Asellus aquaticus and detritus. SIMPER analysis indicated that these four categories together constituted over 65.8% of cumulative dissimilarity in the diet between seasons. Additionally, trophic niche breadth differed significantly between seasons. The study demonstrated that the weatherfish is an opportunistic feeder, consuming large quantities of detritus despite possessing a gut morphology that is atypical of a detritivore. The quantity of detritus in the gut of weatherfish was positively associated with fish total length and varied seasonally, with a greater quantity of detritus in the diet in late summer. These results demonstrate the importance of detritus as a source of energy, particularly during periods of scarcity of alternative prey categories.