Pacific salmon experience prolonged elevation in corticosteroid hormones during important life history events including migration, reproduction, and senescence. These periods of elevated ...corticosteroids correspond with changes to immunity and energy metabolism; therefore, fish may be particularly vulnerable to mortality at these times. Recent studies found that stress-induced cortisol release associated with microbial community shifts in salmonids, raising the question of how longer-term corticosteroid dynamics that accompany life history transitions affect salmonid microbiomes. In this work, we experimentally evaluated the relationships between gut microbiome composition, chronically elevated corticosteroids, and mortality in juvenile Chinook salmon (Oncorhynchus tshawytscha). We found that treatment with slow-release implants of the corticosteroids cortisol or dexamethasone resulted in changes to the gut microbiome. Morbidity was also associated with microbiome composition, suggesting that the gut microbiome reflects individual differences in susceptibility to opportunistic pathogens. Additionally, we analyzed a small number of samples from adult fish at various stages of senescence. Results from these samples suggest that microbiome composition associated with gut integrity, and that the microbial communities of corticosteroid treated juveniles shift in composition toward those of senescent adults. Overall, findings from this work indicate that the gut microbiome correlates with mortality risk during periods of chronic corticosteroid elevation.
Understanding the movement of water through peat is essential for effective conservation and management strategies for peatlands. Saturated hydraulic conductivity,
K
s
, describes water movement ...through the peat profile. However, the spatial variability of
K
s
in tropical peatlands and the effects of land conversion on peat characteristics are poorly understood. Utilizing the slug test method, we estimated hydraulic conductivity in tropical peatlands in West Kalimantan, Indonesia, at three depths (0.75, 3.5, and 5.5 m) across four different land-cover types (undrained forests, recently burned forests, early seral communities, and oil palm (
Elaeis guineensis
Jacq.) plantations). We found strong spatial autocorrelation among measurements collected at our 19 study sites and evaluated the relationship between hydraulic conductivity and land-cover types, peat properties, and depth of measurement with a hierarchical linear model. Hydraulic conductivity varied greatly (
c.
0.001–13.9 m d
−1
). The best approximating model for estimating
K
s
contained depth, forest cover, a depth and forest cover interaction, and the von Post degree of decomposition (
K
s
~ depth + forest + depth × forest + von Post). Parameter estimates indicated that
K
s
was greater in forested than non-forested sites and decreased with increasing depth and decomposition stage. There was no evidence that
K
s
differed among the non-forested sites or was related to other physical and chemical peat properties. Our results suggest that
K
s
should be measured directly in tropical peatlands rather than estimated as a function of peat properties. Additionally, the strong spatial dependence suggests that similar research designs should examine the sample data for spatial dependence and, if necessary, incorporate hierarchical models.
Mycobacterium tuberculosis (MTB) displays the remarkable ability to transition in and out of dormancy, a hallmark of the pathogen’s capacity to evade the immune system and exploit susceptible ...individuals. Uncovering the gene regulatory programs that underlie the phenotypic shifts in MTB during disease latency and reactivation has posed a challenge. We develop an experimental system to precisely control dissolved oxygen levels in MTB cultures in order to capture the transcriptional events that unfold as MTB transitions into and out of hypoxia-induced dormancy. Using a comprehensive genome-wide transcription factor binding map and insights from network topology analysis, we identify regulatory circuits that deterministically drive sequential transitions across six transcriptionally and functionally distinct states encompassing more than three-fifths of the MTB genome. The architecture of the genetic programs explains the transcriptional dynamics underlying synchronous entry of cells into a dormant state that is primed to infect the host upon encountering favorable conditions.
Display omitted
•Reactor enables high-resolution transcriptomics of M. tuberculosis across O2 gradient•147 TFs drive MTB into and out of hypoxia-induced dormancy via distinct sub-states•Robustness, time delay, and anticipatory behavior encoded in transcriptional program•Rv0081-directed feedforward loops play a pivotal role in adaptation to hypoxia
Mycobacterium tuberculosis (MTB) persists within the host by counteracting disparate stressors including hypoxia. Peterson et al. report a transcriptional program that coordinates sequential state transitions to drive MTB in and out of hypoxia-induced dormancy. Among varied properties, this program encodes advanced preparedness to infect the host in favorable conditions.
Bull trout (Salvelinus confluentus) are challenging to detect as a result of the species cryptic behavior and coloration, relatively low densities in complex habitats, and affinity for cold, high ...clarity, low conductivity waters. Bull trout are also closely associated with the stream bed, frequently conceal in substrate, and this concealment behavior is poorly understood. Consequently, population assessments are problematic and biologists and managers often lack quantitative information to accurately describe bull trout distributions, estimate abundance, and assess status and trends; particularly for stream-dwelling populations. During controlled laboratory trials, we recorded concealment, resting, and swimming behavior of juvenile wild bull trout in response to: (1) constant and fluctuating water temperature, (2) presence or absence of light, and (3) substrate size. Light level had the strongest influence on wild fish concealment and more fish concealed as light levels increased from darkness to daylight. Wild fish were 14.5 times less likely to conceal in constant darkness and 4.1 times more likely to conceal in 12 h light x 12 h darkness compared to constant light. Wild fish were 6.2 times less likely to conceal in small (26-51 mm) substrate compared to larger (52-102 mm) substrate. As water temperature increased, fewer wild fish concealed. Knowledge of wild bull trout concealment will improve field sampling protocols and increase detection efficiencies. These data also enhance knowledge of bull trout niche requirements which illuminates ecological differences among species and informs conservation and restoration efforts.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these ...disorders.
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (
= 0.001).
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
Many frameworks have been used to identify environmental flows for sustaining river ecosystems or specific taxa in the face of widespread flow alteration. However, these frameworks largely focus on ...identifying suitable flows and often ignore the important links between management actions, resulting flows, and valued ecosystem or social responses. Structured decision making (SDM) could assist the comparison of environmental flows by providing a mature framework to link management actions to objectives via environmental flow science. We describe SDM and illustrate its application using a case study focused on comparing environmental flow scenarios for the mainstem Willamette River, Oregon. In a short timeframe, SDM was applied to identify objectives, develop empirical and expert opinion‐based models, and compare flow scenarios while accounting for interannual flow variability and partial controllability. No scenario was clearly preferred based on available knowledge, largely because river flows could only be partially controlled through dam operations. Participants agreed that SDM was useful for comparing alternative dam operations, but that refined predictive models and additional objectives were needed to better inform basinwide flow decisions. In our view, SDM can provide more realistic comparisons of environmental flows by accounting for partial controllability and uncertainty, which may result in greater implementation of available flow management actions.
Research Impact Statement: Structured decision making can support environmental flow implementation decisions by linking management options to ecosystem values while accounting for uncertainty.
Infection with Helicobacter pylori is a major risk factor for the development of gastric cancer, and infection with strains carrying the virulence factor CagA significantly increases this risk. To ...investigate the mechanisms by which CagA promotes carcinogenesis, we generated transgenic zebrafish expressing CagA ubiquitously or in the anterior intestine. Transgenic zebrafish expressing either the wild-type or a phosphorylation-resistant form of CagA exhibited significantly increased rates of intestinal epithelial cell proliferation and showed significant upregulation of the Wnt target genes cyclinD1, axin2 and the zebrafish c-myc ortholog myca. Coexpression of CagA with a loss-of-function allele encoding the β-catenin destruction complex protein Axin1 resulted in a further increase in intestinal proliferation. Coexpression of CagA with a null allele of the key β-catenin transcriptional cofactor Tcf4 restored intestinal proliferation to wild-type levels. These results provide in vivo evidence of Wnt pathway activation by CagA downstream of or in parallel to the β-catenin destruction complex and upstream of Tcf4. Long-term transgenic expression of wild-type CagA, but not the phosphorylation-resistant form, resulted in significant hyperplasia of the adult intestinal epithelium. We further utilized this model to demonstrate that oncogenic cooperation between CagA and a loss-of-function allele of p53 is sufficient to induce high rates of intestinal small cell carcinoma and adenocarcinoma, establishing the utility of our transgenic zebrafish model in the study of CagA-associated gastrointestinal cancers.
Background: Pneumococcal disease remains a public health priority in adults. Safety and immunogenicity of 2 different formulations of 15-valent pneumococcal conjugate vaccine (PCV15) containing 13 ...serotypes included in 13-valent pneumococcal conjugate vaccine (PCV13) plus 2 additional serotypes (22F and 33F) were evaluated in adults ≥ 50 years (V114-006; NCT02547649).
Methods: A total of 690 subjects (230/arm) received a single dose of either PCV15 Formulation A, PCV15 Formulation B, or PCV13 and were followed for safety for 14 days postvaccination. Serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) and Immunoglobulin G (IgG) geometric mean concentrations (GMCs) were measured immediately prior and 30 days postvaccination.
Results: Both PCV15 formulations had generally comparable safety profiles to PCV13. Baseline IgG GMCs and OPA GMTs were comparable across vaccination groups. At 30 days postvaccination, both PCV15 formulations induced serotype specific antibodies to all 15 serotypes in the vaccine. IgG GMCs and OPA GMTs in recipients of either PCV15 formulation were non-inferior (≤ 2-fold margin) to those measured in recipients of PCV13 for shared serotypes and superior (> 1.0-fold difference) for serotypes unique to PCV15. Formulation B generally induced higher immune responses than Formulation A.
Conclusion: In healthy adults ≥ 50 years of age, both new formulations of PCV15 displayed acceptable safety profiles and induced serotype-specific immune responses comparable to PCV13.
Abstract
Background
Prevention of respiratory syncytial virus (RSV) disease in infants is an unmet vaccine need, and maternal immunization is a potential strategy to address this need. This study ...evaluated concomitant administration of RSV stabilized prefusion F subunit vaccine (RSVpreF) and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed (Tdap) in healthy, nonpregnant women 18‒49 years of age.
Methods
In this phase 2b, multicenter, placebo-controlled, observer-blind, noninferiority study, participants were randomized to receive RSVpreF in a range of doses and formulations with Tdap or alone, or Tdap alone. Safety and immunogenicity were assessed.
Results
Local reactions and systemic events were generally similar across vaccine groups. Noninferiority of anti-RSV-A and anti-RSV-B immune responses induced by RSVpreF with Tdap was demonstrated compared to RSVpreF alone. Noninferiority of anti-diphtheria toxoid and anti-tetanus toxoid immune responses after administration of RSVpreF with Tdap was demonstrated compared to Tdap alone; noninferiority was not met for anti-pertussis component responses.
Conclusions
RSVpreF was safe and well tolerated when administered with Tdap or alone in nonpregnant women 18‒49 years of age. Immune responses induced by Tdap administered with RSVpreF were noninferior for the tetanus and diphtheria components of Tdap, but not for pertussis.
Clinical Trials Registration
NCT04071158.
Respiratory syncytial virus stabilized prefusion F subunit vaccine (RSVpreF) was safe and well tolerated when administered with Tdap or alone in nonpregnant women. Tdap-induced immune responses with concomitant RSVpreF were noninferior for tetanus and diphtheria, but not the pertussis component.
Prespawn mortality (PSM) presents a major problem for the recovery of spring Chinook Salmon (Oncorhynchus tshawytscha) populations. In the Willamette River, Oregon, PSM exceeds 90% in some years but ...factors explaining it are not well understood. We examined intestinal tissue samples using histological slides from over 783 spring Chinook Salmon collected between 2009 and 2021, which included tissues from PSM fish, artificially spawned captive broodstock (BS) and normal river run fish, comprised of trapped (Live) and naturally post-spawned river (RPS) fish collected from the river. We observed degeneration of the intestinal epithelium and loss of villous structure, with concurrent severe enteritis. A natural progression of decline in epithelial integrity (EI) through the summer and fall until spawning and subsequent death was also observed. Live fish exhibited high EI scores (mean = 68%), BS exhibited variable EI scores (35%) and RPS exhibited severe loss of EI (14%). PSM fish exhibited prominent loss of intestinal epithelium with EI scores (13%), very similar to RPS fish, despite having been collected earlier in the year. Hence, we argue that low EI scores are strongly linked with PSM. Ceratonova shasta and Enterocytozoon schreckii were common in all groups, but neither were linked to either PSM or a decline in EI.
PDF
