Habitat disturbance, a common consequence of anthropogenic land use practices, creates human–animal interfaces where humans, wildlife, and domestic species can interact. These altered habitats can ...influence host–microbe dynamics, leading to potential downstream effects on host physiology and health. Here, we explored the effect of ecological overlap with humans and domestic species and infection with the protozoan parasite Giardia duodenalis on the bacteria of black and gold howler monkeys (Alouatta caraya), a key sentinel species, in northeastern Argentina. Fecal samples were screened for Giardia duodenalis infection using a nested PCR reaction, and the gut bacterial community was characterized using 16S rRNA gene amplicon sequencing. Habitat type was correlated with variation in A. caraya gut bacterial community composition but did not affect gut bacterial diversity. Giardia presence did not have a universal effect on A. caraya gut bacteria across habitats, perhaps due to the high infection prevalence across all habitats. However, some bacterial taxa were found to vary with Giardia infection. While A. caraya's behavioral plasticity and dietary flexibility allow them to exploit a range of habitat conditions, habitats are generally becoming more anthropogenically disturbed and, thus, less hospitable. Alterations in gut bacterial community dynamics are one possible indicator of negative health outcomes for A. caraya in these environments, since changes in host–microbe relationships due to stressors from habitat disturbance may lead to negative repercussions for host health. These dynamics are likely relevant for understanding organism responses to environmental change in other mammals.
Habitat disturbance, a common consequence of anthropogenic land use practices, creates human–animal interfaces where humans, wildlife, and domestic species can interact. These altered habitats can influence host–microbe dynamics, leading to potential downstream effects on host physiology and health. Here, we explored the effect of ecological overlap with humans and domestic species and infection with the protozoan parasite Giardia duodenalis on the bacteria of black and gold howler monkeys (Alouatta caraya), a key sentinel species, in northeastern Argentina. Fecal samples were screened for Giardia duodenalis infection using a nested PCR reaction, and the gut bacterial community was characterized using 16S rRNA gene amplicon sequencing. Habitat type was correlated with variation in A. caraya gut bacterial community composition but did not affect gut bacterial diversity. Giardia presence did not have a universal effect on A. caraya gut bacteria across habitats, perhaps due to the high infection prevalence across all habitats. However, some bacterial taxa were found to vary with Giardia infection. While A. caraya's behavioral plasticity and dietary flexibility allow them to exploit a range of habitat conditions, habitats are generally becoming more anthropogenically disturbed and, thus, less hospitable. Alterations in gut bacterial community dynamics are one possible indicator of negative health outcomes for A. caraya in these environments, since changes in host–microbe relationships due to stressors from habitat disturbance may lead to negative repercussions for host health. These dynamics are likely relevant for understanding organism responses to environmental change in other mammals.
Sound management of bird populations rests upon an adequate understanding of their population dynamics. Our study evaluated recruitment and population growth rates of 14 American common eider ...(Somateria mollissima dresseri) colonies from Labrador, Nova Scotia, Quebec, Canada, and Maine, USA, during various periods between 1970 and 2019. We used Pradel mark-recapture models to estimate colony-specific growth rates and the relative contributions of survival and recruitment on growth. We also validated this approach using annual nest counts (~8,000 pairs) conducted between 2003 and 2019 during down harvest operations in 3 colonies located in the Saint Lawrence estuary in Quebec. There was generally a good agreement between estimates derived using the 2 approaches. We considered that capture-recapture data were suitable to estimate population trends of common eiders in other colonies, especially for colonies where accurate nest monitoring is impaired by dense vegetation. The breeding abundance declined at major colonies in Maine and Nova Scotia and increased or was stable in Quebec and Labrador. Female survival contributed the most to population growth, but variation in recruitment among colonies was more important than variation in survival to explain population growth. Management measures should thus strive to maximize local recruitment in colonies with declining populations. The assumption that apparent survival probabilities were homogeneous throughout an individual capture history was violated at several colonies in Quebec and Labrador. Using recaptures and band recoveries, we showed that the lower apparent survival for newly marked individuals compared to females that had been recaptured at least once was caused by a difference in site fidelity rather than true survival. But <1% of recaptured females dispersed to another colony for breeding, indicating that the lower site fidelity could be related to heterogeneity in capture probability among individuals.
Abstract
Across the globe, 2-3% of humans carry the
p.Ser132Pro
single nucleotide polymorphism in
MLKL
, the terminal effector protein of the inflammatory form of programmed cell death, necroptosis. ...Here we show that this substitution confers a gain in necroptotic function in human cells, with more rapid accumulation of activated MLKL
S132P
in biological membranes and MLKL
S132P
overriding pharmacological and endogenous inhibition of MLKL. In mouse cells, the equivalent
Mlkl S131P
mutation confers a gene dosage dependent reduction in sensitivity to TNF-induced necroptosis in both hematopoietic and non-hematopoietic cells, but enhanced sensitivity to IFN-β induced death in non-hematopoietic cells. In vivo,
Mlkl
S131P
homozygosity reduces the capacity to clear
Salmonella
from major organs and retards recovery of hematopoietic stem cells. Thus, by dysregulating necroptosis, the S131P substitution impairs the return to homeostasis after systemic challenge. Present day carriers of the
MLKL S132P
polymorphism may be the key to understanding how MLKL and necroptosis modulate the progression of complex polygenic human disease.
Focal intracranial infections (epidural abscesses, subdural empyemas, and intraparenchymal abscesses) are uncommon complications of sinusitis and otitis media but can be associated with significant ...morbidity. Treatment typically requires neurosurgical and otolaryngological interventions in combination with antibiotic treatment. Historically, children have presented to the authors' pediatric referral center with sinusitis- or otitis media-related intracranial infections in low numbers. However, since the onset of the COVID-19 pandemic, the incidence of intracranial pyogenic complications has increased at this center. The objective of this study was to compare the epidemiology, severity, microbial causes, and management of pediatric sinusitis- and otitis-related intracranial infections in the periods before and during the COVID-19 pandemic.
All patients 21 years of age or younger who presented with an intracranial infection in the setting of sinusitis or otitis media and who underwent neurosurgical treatment at Connecticut Children's from January 2012 to December 2022 were retrospectively reviewed. Demographic, clinical, laboratory, and radiological data were systematically collated, and variables before and during COVID-19 were compared statistically.
Overall, 18 patients were treated for sinusitis-related (n = 16) or otitis media-related (n = 2) intracranial infections during the study period. Ten patients (56%) presented from January 2012 to February 2020, none from March 2020 to June 2021, and 8 (44%) from July 2021 to December 2022. There were no significant demographic differences between the pre-COVID-19 and COVID-19 cohorts. The 10 patients in the pre-COVID-19 cohort underwent a total of 15 neurosurgical and 10 otolaryngological procedures, while the 8 patients in the COVID-19 cohort underwent a total of 12 neurosurgical and 10 otolaryngological procedures. Surgically obtained wound cultures yielded a variety of organisms; Streptococcus constellatus/S. anginosus/S. intermedius were more prevalent in the COVID-19 cohort (87.5% vs 0%, p < 0.001) as was Parvimonas micra (62.5% vs 0%, p = 0.007).
At an institutional level, there has been an approximately threefold increase in cases of sinusitis- and otitis media-related intracranial infections during the COVID-19 pandemic. Multicenter studies are needed to confirm this observation and to investigate whether the mechanisms of infection are related directly to SARS-CoV-2, changes in the respiratory flora, or delayed care. The next steps will include expansion of this study to other pediatric centers throughout the United States and Canada.
IMPORTANCE: Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation. Its retinal phenotype is not well described but could be ...important for disease recognition because it appears to be a consistent primary presenting feature. OBJECTIVE: To investigate a series of patients with the same mutation in the SRD5A3 gene and thereby characterize its retinal manifestations and other associated features. DESIGN, SETTING AND PARTICIPANTS: Seven affected individuals from 4 unrelated families with early-onset retinal dystrophy as a primary manifestation underwent comprehensive ophthalmic assessment, including retinal imaging and electrodiagnostic testing. Developmental and systemic findings were also recorded. Molecular genetic approaches, including targeted next-generation sequencing, autozygosity mapping, and apex microarray, were tried to reach a diagnosis; all participants were mutation negative. Whole-exome sequencing or whole-genome sequencing was used to identify the causative variant. Biochemical profiling was conducted to confirm a CDG type I defect. Patient phenotype data were collected over the course of ophthalmic follow-up, spanning a period of 20 years, beginning March 20, 1997, through September 15, 2016. MAIN OUTCOMES AND MEASURES: Detailed clinical phenotypes as well as genetic and biochemical results. RESULTS: The cohort consisted of 7 participants (5 females and 2 males) whose mean (SD) age at the most recent examination was 17.1 (3.9) years and who were all of South Asian ethnicity. Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family. Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean SD best-corrected visual acuity, +0.95 0.34 logMAR 20/180 Snellen), childhood-onset nyctalopia, myopia (mean SD refractive error, –6.71 –4.22), and nystagmus. Six of the 7 patients had learning difficulties and psychomotor delay. Fundus autofluorescence imaging and optical coherence tomographic scans were abnormal in all patients, and electrodiagnostic testing revealed rod and cone dysfunction in the 5 patients tested. CONCLUSIONS AND RELEVANCE: Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment. SRD5A3 and other glycosylation disorder genes should be considered as a cause of retinal dystrophy even when systemic features are mild. Further delineation of SRD5A3-associated eye phenotypes can help inform genetic counseling for prognostic estimation of visual loss and disease progression.
Objectives
Systemic inflammatory response syndrome (SIRS) is a frequent complication of cardiopulmonary bypass (CPB). SIRS is associated with significant morbidity and mortality, but its pathogenesis ...remains incompletely understood, and as a result, biomarkers are lacking and treatment remains expectant and supportive. This study aimed to understand the pathophysiological mechanisms driving SIRS induced by CPB and identify novel therapeutic targets that might reduce systemic inflammation and improve patient outcomes.
Methods
Twenty‐one patients undergoing cardiac surgery and CPB were recruited, and blood was sampled before, during and after surgery. SIRS was defined using the American College of Chest Physicians/Society of Critical Care Medicine criteria. We performed immune cell profiling and whole blood transcriptomics and measured individual mediators in plasma/serum to characterise SIRS induced by CPB.
Results
Nineteen patients fulfilled criteria for SIRS, with a mean duration of 2.7 days. Neutrophil numbers rose rapidly with CPB and remained elevated for at least 48 h afterwards. Transcriptional signatures associated with neutrophil activation and degranulation were enriched during CPB. We identified a network of cytokines governing these transcriptional changes, including granulocyte colony‐stimulating factor (G‐CSF), a regulator of neutrophil production and function.
Conclusions
We identified neutrophils and G‐CSF as major regulators of CPB‐induced systemic inflammation. Short‐term targeting of G‐CSF could provide a novel therapeutic strategy to limit neutrophil‐mediated inflammation and tissue damage in SIRS induced by CPB.
Systemic inflammatory response syndrome (SIRS) is a major complication associated with cardiopulmonary bypass (CPB). In this study, we used whole blood transcriptomics to reveal neutrophils and G‐CSF as major regulators of CPB‐induced systemic inflammation. Our results suggest that short‐term targeting of G‐CSF could provide a novel therapeutic strategy to limit neutrophil‐mediated inflammation and tissue damage in SIRS induced by CPB.
Explosive volcanic eruptions radiate seismic waves as a consequence of pressure and shear traction changes within the conduit/chamber system. Kinematic source inversions utilize these waves to ...determine equivalent seismic force and moment tensor sources, but relation to eruptive processes is often ambiguous and nonunique. In this work, we provide an alternative, forward modeling approach to calculate moment tensor and force equivalents of a model of eruptive conduit flow and chamber depressurization. We explain the equivalence of two seismic force descriptions, the first in terms of traction changes on conduit/chamber walls, and the second in terms of changes in magma momentum, weight, and momentum transfer to the atmosphere. Eruption onset is marked by a downward seismic force, associated with loss of restraining shear tractions from fragmentation. This is followed by a much larger upward seismic force from upward drag of ascending magma and reduction of magma weight remaining in the conduit/chamber system. The static force is upward, arising from weight reduction. We calculate synthetic seismograms to examine the expression of eruptive processes at different receiver distances. Filtering these synthetics to the frequency band typically resolved by broadband seismometers produces waveforms similar to very long period seismic events observed in strombolian and vulcanian eruptions. However, filtering heavily distorts waveforms, accentuating processes in early, unsteady parts of eruptions and eliminating information about longer (ultra long period time scale depressurization and weight changes that dominate unfiltered seismograms. Our workflow can be utilized to directly and quantitatively connect eruption models with seismic observations.
Plain Language Summary
Volcanic eruptions radiate seismic waves that can be recorded by seismometers placed on and around a volcano. Analysis of seismic data enables one to study eruptions, in particular the processes occurring in the magma‐filled conduit and chamber that feeds the eruption. One process of particular interest is fragmentation, in which magma containing a mixture of liquid melt and gas bubbles breaks apart in the conduit and erupts explosively from the vent. We perform computer simulations of explosive eruptions and then use the output of those simulations to predict seismic radiation. We examine the seismograms produced by this workflow to identify features that are diagnostic of process, such as fragmentation, that occur at different times in the eruption. These predictions will guide interpretation of seismic data from real eruptions.
Key Points
We provide expressions for the seismic force in eruptions that can be evaluated using outputs from unsteady conduit flow models
We generate and analyze seismograms from vulcanian eruption models to identify the seismic expression of fragmentation and other processes
Our modeling suggests that eruptive mass could be inferred by extending seismic inversions to periods of minutes to tens of minutes
Isoprene oxidation schemes vary greatly among gas-phase chemical mechanisms, with potentially significant ramifications for air quality modeling and interpretation of satellite observations in ...biogenic-rich regions. In this study, in situ observations from the 2013 SENEX mission are combined with a constrained 0-D photochemical box model to evaluate isoprene chemistry among five commonly used gas-phase chemical mechanisms: CB05, CB6r2, MCMv3.2, MCMv3.3.1, and a recent version of GEOS-Chem. Mechanisms are evaluated and inter-compared with respect to formaldehyde (HCHO), a high-yield product of isoprene oxidation. Though underestimated by all considered mechanisms, observed HCHO mixing ratios are best reproduced by MCMv3.3.1 (normalized mean bias = −15%), followed by GEOS-Chem (−17%), MCMv3.2 (−25%), CB6r2 (−32%) and CB05 (−33%). Inter-comparison of HCHO production rates reveals that major restructuring of the isoprene oxidation scheme in the Carbon Bond mechanism increases HCHO production by only ∼5% in CB6r2 relative to CB05, while further refinement of the complex isoprene scheme in the Master Chemical Mechanism increases HCHO production by ∼16% in MCMv3.3.1 relative to MCMv3.2. The GEOS-Chem mechanism provides a good approximation of the explicit isoprene chemistry in MCMv3.3.1 and generally reproduces the magnitude and source distribution of HCHO production rates. We analytically derive improvements to the isoprene scheme in CB6r2 and incorporate these changes into a new mechanism called CB6r2-UMD, which is designed to preserve computational efficiency. The CB6r2-UMD mechanism mimics production of HCHO in MCMv3.3.1 and demonstrates good agreement with observed mixing ratios from SENEX (−14%). Improved simulation of HCHO also impacts modeled ozone: at ∼0.3 ppb NO, the ozone production rate increases ∼3% between CB6r2 and CB6r2-UMD, and rises another ∼4% when HCHO is constrained to match observations.
•All considered mechanisms underestimate observed HCHO by at least 15%.•Mechanistic differences are driven by second- and late-generation isoprene oxidation.•Recommendations are provided for CB6r2 and incorporated into new mechanism CB6r2-UMD.•Simulated HCHO impacts modeled ozone production rates.
Enumeration of circulating tumor cells (CTCs) from cancer patient blood is an established diagnostic assay used to evaluate patient status as a singleplex test. However, in the coming age of ...personalized medicine, multiplex analysis of patient CTCs, including proteomic and genomic techniques, will have to be integrated with CTC isolation platform technologies. Advancements in microfabrication have demonstrated that CTCs can be isolated and analyzed using microfluidic lab-on-a-chip devices. However, to date, most microfluidic devices are either still in the development phase, not applicable to all clinical tests, or are not commercially available. To overcome these discrepancies, we describe an all-in-one device for the isolation and multiplexing of clinically applicable CTC assays. Microfilters present an ideal lab-on-a-chip platform for analysis of CTCs as non-toxic and inert materials allow for a multitude of tests from cell growth through clinical staining techniques, all without background interference. Lithographically fabricated microfilters, can be made with high porosity, precise pore dimensions, arrayed pore distribution, and optimized for CTC size-based isolation. In this study we describe microfilter use in isolation and
analysis of CTCs using multiple sequential techniques including culture, FISH, histopathological analysis, H&E staining, photobleaching and re-staining. Further, as a proof of principle, we then describe the ability to quantitatively release patient derived CTCS from the microfilters for potential use in downstream genomic/proteomic analysis.
Proteinase 3 (PR3), the autoantigen in granulomatosis with polyangiitis, is expressed at the plasma membrane of resting neutrophils, and this membrane expression increases during both activation and ...apoptosis. Using surface plasmon resonance and protein-lipid overlay assays, this study demonstrates that PR3 is a phosphatidylserine-binding protein and this interaction is dependent on the hydrophobic patch responsible for membrane anchorage. Molecular simulations suggest that PR3 interacts with phosphatidylserine via a small number of amino acids, which engage in long lasting interactions with the lipid heads. As phosphatidylserine is a major component of microvesicles (MVs), this study also examined the consequences of this interaction on MV production and function. PR3-expressing cells produced significantly fewer MVs during both activation and apoptosis, and this reduction was dependent on the ability of PR3 to associate with the membrane as mutating the hydrophobic patch restored MV production. Functionally, activation-evoked MVs from PR3-expressing cells induced a significantly larger respiratory burst in human neutrophils compared with control MVs. Conversely, MVs generated during apoptosis inhibited the basal respiratory burst in human neutrophils, and those generated from PR3-expressing cells hampered this inhibition. Given that membrane expression of PR3 is increased in patients with granulomatosis with polyangiitis, MVs generated from neutrophils expressing membrane PR3 may potentiate oxidative damage of endothelial cells and promote the systemic inflammation observed in this disease.
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