Geographic turnover in community composition is created and maintained by eco-evolutionary forces that limit the ranges of species. One such force may be antagonistic interactions among hosts and ...parasites, but its general importance is unknown. Understanding the processes that underpin turnover requires distinguishing the contributions of key abiotic and biotic drivers over a range of spatial and temporal scales. Here, we address these challenges using flexible, nonlinear models to identify the factors that underlie richness (alpha diversity) and turnover (beta diversity) patterns of interacting host and parasite communities in a global biodiversity hot spot. We sampled 18 communities in the Peruvian Andes, encompassing ∼1,350 bird species and ∼400 hemosporidian parasite lineages, and spanning broad ranges of elevation, climate, primary productivity, and species richness. Turnover in both parasite and host communities was most strongly predicted by variation in precipitation, but secondary predictors differed between parasites and hosts, and between contemporary and phylogenetic timescales. Host communities shaped parasite diversity patterns, but there was little evidence for reciprocal effects. The results for parasite communities contradicted the prevailing view that biotic interactions filter communities at local scales while environmental filtering and dispersal barriers shape regional communities. Rather, subtle differences in precipitation had strong, fine-scale effects on parasite turnover while host-community effects only manifested at broad scales. We used these models to map bird and parasite turnover onto the ecological gradients of the Andean landscape, illustrating beta-diversity hot spots and their mechanistic underpinnings.
This study sought to determine if high sodium (HS) intake in salt resistant (SR) individuals attenuates upper limb arterial dilation in response to reactive (occlusion) and active (exercise) ...hyperemia, two stimuli with varying vasodilatory mechanisms, and the role of oxidative stress in this response. Ten young, SR participants (9 males, 1 female) consumed a 7-day HS (6,900 mg/day) and a 7-day recommended sodium intake (RI: 2,300 mg/day) diet in a randomized order. On the last day of each diet, brachial artery (BA) function was evaluated via reactive (RH-FMD: 5 min of cuff occlusion) and active handgrip (HG) exercise hyperemia after consumption of both placebo (PL) and antioxidants (AO). The HS diet significantly elevated sodium excretion (
< 0.05), but mean arterial blood pressure was unchanged. During the PL condition, the HS diet significantly reduced RH-FMD when compared with RI diet (
= 0.01), but this reduction was significantly restored (
= 0.01) when supplemented with AO (HS + PL: 5.9 ± 3.4; HS + AO: 8.2 ± 2.7; RI + PL: 8.9 ± 4.7; RI + AO: 7.0 ± 2.1%). BA shear-to-dilation slopes, evaluated across all HG exercise workloads, were not significantly different across sodium intervention or AO supplementation. In SR individuals, HS intake impaired BA function when assessed via RH-FMD, but was restored with acute AO consumption suggesting oxidative stress as a contributor to this dysfunction. However, exercise-induced BA dilation was unaltered, potentially implicating an inability of HS intake to influence the mechanisms responsible for effectively maintaining skeletal muscle perfusion during exercise.
This study examined if high sodium (HS) intake in salt resistant (SR) individuals attenuates brachial artery (BA) flow-mediated dilation in response to reactive (occlusion) and active (exercise) hyperemia. In SR individuals, HS intake impaired reactive hyperemia-induced BA dilation, but not exercise-induced BA dilation. This finding suggests that although brachial artery nitric oxide bioavailability may be reduced following HS intake, the redundant mechanisms associated with adequate upper limb blood flow regulation during exercise are maintained.
Infrared Sky Brightness Monitors for Antarctica Storey, J. W. V.; Ashley, M. C. B.; Boccas, M. ...
Publications of the Astronomical Society of the Pacific,
06/1999, Letnik:
111, Številka:
760
Journal Article
Recenzirano
Two sky brightness monitors—one for the near‐infrared and one for the mid‐infrared—have been developed for site survey work in Antarctica. The instruments, which we refer to as the NISM ...(Near‐Infrared Sky Monitor) and the MISM (Mid‐Infrared Sky Monitor), are part of a suite of instruments being deployed in the Automated Astrophysical Site‐Testing Observatory (AASTO). The chief design constraints include reliable, autonomous operation, low power consumption, and of course the ability to operate under conditions of extreme cold. The instruments are currently operational at the Amundsen‐Scott South Pole Station, prior to deployment at remote, unattended sites on the high antarctic plateau.
The thymus represents the major site of the production and generation of T cells expressing αβ-type T-cell antigen receptors. Age-related involution may affect the ability of the thymus to ...reconstitute T cells expressing CD4 cell-surface antigens that are lost during HIV infection; this effect has been seen after chemotherapy and bone-marrow transplantation,. Adult HIV-infected patients treated with highly active antiretroviral therapy (HAART) show a progressive increase in their number of naive CD4-positive T cells,. These cells could arise through expansion of existing naive T cells in the periphery or through thymic production of new naive T cells,. Here we quantify thymic output by measuring the excisional DNA products of TCR-gene rearrangement. We find that, although thymic function declines with age, substantial output is maintained into late adulthood. HIV infection leads to a decrease in thymic function that can be measured in the peripheral blood and lymphoid tissues. In adults treated with HAART, there is a rapid and sustained increase in thymic output in most subjects. These results indicate that the adult thymus can contribute to immune reconstitution following HAART.
Study objective The incidence of Clostridium difficile infection has increased and has been observed among persons from the community who have not been exposed to antibiotics or health care settings. ...Our aims are to determine prevalence of C difficile infection among emergency department (ED) patients with diarrhea and the prevalence among patients without traditional risk factors. Methods We conducted a prospective observational study of patients aged 2 years or older with diarrhea (≥3 episodes/24 hours) and no vomiting in 10 US EDs (2010 to 2013). We confirmed C difficile infection by positive stool culture result and toxin assay. C difficile infection risk factors were antibiotic use or overnight health care stay in the previous 3 months or previous C difficile infection. We typed strains with pulsed-field gel electrophoresis. Results Of 422 participants, median age was 46 years (range 2 to 94 years), with median illness duration of 3.0 days and 43.4% having greater than or equal to 10 episodes of diarrhea during the previous 24 hours. At least one risk factor for C difficile infection was present in 40.8% of participants; 25.9% were receiving antibiotics, 26.9% had health care stay within the previous 3 months, and 3.3% had previous C difficile infection. Forty-three participants (10.2%) had C difficile infection; among these, 24 (55.8%) received antibiotics and 19 (44.2%) had health care exposure; 17 of 43 (39.5%) lacked any risk factor. Among participants without risk factors, C difficile infection prevalence was 6.9%. The most commonly identified North American pulsed-field gel electrophoresis (NAP) strains were NAP type 1 (23.3%) and NAP type 4 (16.3%). Conclusion Among mostly adults presenting to US EDs with diarrhea and no vomiting, C difficile infection accounted for approximately 10%. More than one third of patients with C difficile infection lacked traditional risk factors for the disease. Among participants without traditional risk factors, prevalence of C difficile infection was approximately 7%.
18S rRNA is a biomarker that provides an alternative to thick blood smears in controlled human malaria infection (CHMI) trials. We reviewed data from CHMI trials at non-endemic sites that used blood ...smears and
18S rRNA/rDNA biomarker nucleic acid tests (NATs) for time to positivity. We validated a multiplex quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for
18S rRNA, prospectively compared blood smears and qRT-PCR for three trials, and modeled treatment effects at different biomarker-defined parasite densities to assess the impact on infection detection, symptom reduction, and measured intervention efficacy. Literature review demonstrated accelerated NAT-based infection detection compared with blood smears (mean acceleration: 3.2-3.6 days). For prospectively tested trials, the validated
18S rRNA qRT-PCR positivity was earlier (7.6 days; 95% CI: 7.1-8.1 days) than blood smears (11.0 days; 95% CI: 10.3-11.8 days) and significantly preceded the onset of grade 2 malaria-related symptoms (12.2 days; 95% CI: 10.6-13.3 days). Discrepant analysis showed that the risk of a blood smear-positive, biomarker-negative result was negligible. Data modeling predicted that treatment triggered by specific biomarker-defined thresholds can differentiate complete, partial, and non-protective outcomes and eliminate many grade 2 and most grade 3 malaria-related symptoms post-CHMI.
18S rRNA is a sensitive and specific biomarker that can justifiably replace blood smears for infection detection in CHMI trials in non-endemic settings. This study led to biomarker qualification through the U.S. Food and Drug Administration for use in CHMI studies at non-endemic sites, which will facilitate biomarker use for the qualified context of use in drug and vaccine trials.
Familial hypertrophic cardiomyopathy is a common inherited cardiovascular disorder in people. Many causal mutations have been identified, but about 40% of cases do not have a known causative ...mutation. Mutations in the ALMS1 gene are associated with the development of Alstrom syndrome, a multisystem familial disease that can include cardiomyopathy (dilated, restrictive). Hypertrophic cardiomyopathy has not been described. The ALMS1 gene is a large gene that encodes for a ubiquitously expressed protein. The function of the protein is not well understood although it is believed to be associated with energy metabolism and homeostasis, cell differentiation and cell cycle control. The ALMS1 protein has also been shown to be involved in the regulation of cell cycle proliferation in perinatal cardiomyocytes. Although cardiomyocyte cell division and replication in mammals generally declines soon after birth, inhibition of ALMS1 expression in mice lead to increased cardiomyocyte proliferation, and deficiency of Alstrom protein has been suggested to impair post-natal cardiomyocyte cell cycle arrest. Here we describe the association of familial hypertrophic cardiomyopathy in Sphynx cats with a novel ALMS1 mutation.
A G/C variant was identified in exon 12 (human exon 13) of the ALMS1 gene in affected cats and was positively associated with the presence of hypertrophic cardiomyopathy in the feline population (p < 0.0001). The variant was predicted to change a highly conserved nonpolar Glycine to a positively charged Arginine. This was predicted to be a deleterious change by three in silico programs. Protein prediction programs indicated that the variant changed the protein structure in this region from a coil to a helix. Light microscopy findings included myofiber disarray with interstitial fibrosis with significantly more nuclear proliferative activity in the affected cats than controls (p < 0.0001).
This study demonstrates a novel form of cardiomyopathy associated with ALMS1 in the cat. Familial hypertrophic cardiomyopathy is a disease of genetic heterogeneity; many of the known causative genes encoding for sarcomeric proteins. Our findings suggest that variants in genes involved with cardiac development and cell regulation, like the ALMS1 gene, may deserve further consideration for association with familial hypertrophic cardiomyopathy.
Perceived credibility of social media data (i.e., a Twitter post) was compared to more traditional collateral sources in criminal responsibility evaluations using independent samples of laypersons ...and forensic experts. Overall, results suggested greater skepticism toward social media relative to two other sources, particularly when information suggested a mental illness. Both samples, however, viewed the tweet as potentially useful. Notably, both studies were limited by the use of an experimental design that was intended to capture initial impressions rather than fully mimic standard assessment and courtroom processes. We advocate a cautious but open-minded approach when considering social media data as collateral.
Prognostic indicators, treatments, and survival estimates vary by cancer type. Therefore, disease-specific models are needed to estimate patient survival. Our primary aim was to develop models to ...estimate survival duration after treatment for skeletal-related events (SREs) (symptomatic bone metastasis, including impending or actual pathologic fractures) in men with metastatic bone disease due to prostate cancer. Such disease-specific models could be added to the PATHFx clinical-decision support tool, which is available worldwide, free of charge. Our secondary aim was to determine disease-specific factors that should be included in an international cancer registry.
We analyzed records of 438 men with metastatic prostate cancer who sustained SREs that required treatment with radiotherapy or surgery from 1989-2017. We developed and validated 6 models for 1-, 2-, 3-, 4-, 5-, and 10-year survival after treatment. Model performance was evaluated using calibration analysis, Brier scores, area under the receiver operator characteristic curve (AUC), and decision curve analysis to determine the models' clinical utility. We characterized the magnitude and direction of model features.
The models exhibited acceptable calibration, accuracy (Brier scores < 0.20), and classification ability (AUCs > 0.73). Decision curve analysis determined that all 6 models were suitable for clinical use. The order of feature importance was distinct for each model. In all models, 3 factors were positively associated with survival duration: younger age at metastasis diagnosis, proximal prostate-specific antigen (PSA) < 10 ng/mL, and slow-rising alkaline phosphatase velocity (APV).
We developed models that estimate survival duration in patients with metastatic bone disease due to prostate cancer. These models require external validation but should meanwhile be included in the PATHFx tool. PSA and APV data should be recorded in an international cancer registry.
Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus endemic in the Asia Pacific region. Despite use of several highly effective vaccines, it is estimated that up to 44,000 new cases of ...Japanese encephalitis (JE) occur every year including 14,000 deaths and 24,000 survivors with permanent sequelae. Humoral immunity induced by vaccination is critical for effective protection. Potently neutralizing antibodies reactive with the JEV envelope (E) protein are important since protective immune responses induced by both live-attenuated and inactivated JE vaccines target the E protein. Our understanding of how vaccine-induced humoral immunity protects vaccinees from morbidity and mortality is, however, limited and largely obtained from in vitro studies. With the exception of neurovirulence mouse models, very few platforms are available for evaluating the protective efficacy of neutralizing antibodies against JEV in vivo. Swine are a major amplifying host in the natural JEV transmission cycle and develop multiple pathological outcomes similar to humans infected with JEV. In this study, prophylactic passive immunization was performed in a miniature swine model, using two vaccination-induced monoclonal antibodies (mAb), JEV-31 and JEV-169. These were selected as representatives for antibodies reactive with the major antigenic structures in the E protein of JEV and related flaviviruses. JEV-31 recognizes the lateral ridge of E protein domain III (EDIII) whilst JEV-169 has a broad footprint of binding involving residues throughout domains I (EDI) and II (EDII) of the E protein. Detection of neutralizing antibodies in the serum of immunized animals mimics the presence of neutralizing antibodies in vaccinated individuals. Passive immunization with both mAbs significantly reduced the severity of diseases that resemble the symptoms of human JE including fever, viremia, viral shedding, systemic infection, and neuroinvasion. In contrast to the uniformed decrease of viral loads in lymphoid and central nervous systems, distinct kinetics in the onset of fever and viremia between animals receiving JEV-31 and JEV-169 suggest potential differences in immune protection mechanisms between anti-EDI and anti-EDIII neutralizing antibodies elicited by vaccination. Our data demonstrate the feasibility of using swine models in characterizing the protective humoral immunity against JEV and increase our understanding of how clonal populations of anti-E mAbs derived from JE vaccination protect against infection in vivo.
•Protective efficacy of anti-Japanese encephalitis virus monoclonal antibodies was demonstrated.•Passive immunization of neutralizing antibodies reduced systemic and neurotropic diseases in a miniature swine model.•Antibodies reactive with interdomain epitopes and envelope protein domain III differentially modulated viremia in vivo.
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