450 research outputs found
Fighting a losing battle: Vigorous immune response countered by pathogen suppression of host defenses in the chytridiomycosis-susceptible frog Atelopus zeteki
The emergence of the disease chytridiomycosis caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd) has been implicated in dramatic global amphibian declines. Although many species have undergone catastrophic declines and/or extinctions, others appear to be unaffected or persist
at reduced frequencies after Bd outbreaks. The reasons behind this variance in disease outcomes are poorly
understood: differences in host immune responses have been proposed, yet previous studies suggest a lack
of robust immune responses to Bd in susceptible species. Here, we sequenced transcriptomes from clutchmates
of a highly susceptible amphibian, Atelopus zeteki, with different infection histories. We found
significant changes in expression of numerous genes involved in innate and inflammatory responses in
infected frogs despite high susceptibility to chytridiomycosis. We show evidence of acquired immune
responses generated against Bd, including increased expression of immunoglobulins and major histocompatibility
complex genes. In addition, fungal-killing genes had significantly greater expression in frogs
previously exposed to Bd compared with Bd-naïve frogs, including chitinase and serine-type proteases.
However, our results appear to confirm recent in vitro evidence of immune suppression by Bd, demonstrated
by decreased expression of lymphocyte genes in the spleen of infected compared with control frogs. We propose susceptibility to chytridiomycosis is not due to lack of Bd-specific immune responses but instead is caused by failure of those responses to be effective. Ineffective immune pathway activation and timing of antibody production are discussed as potential mechanisms. However, in light of our findings,suppression of key immune responses by Bd is likely an important factor in the lethality of this fungus
Coordination-driven magnetic-to-nonmagnetic transition in manganese doped silicon clusters
The interaction of a single manganese impurity with silicon is analyzed in a
combined experimental and theoretical study of the electronic, magnetic, and
structural properties of manganese-doped silicon clusters. The structural
transition from exohedral to endohedral doping coincides with a quenching of
high-spin states. For all geometric structures investigated, we find a similar
dependence of the magnetic moment on the manganese coordination number and
nearest neighbor distance. This observation can be generalized to manganese
point defects in bulk silicon, whose magnetic moments fall within the observed
magnetic-to-nonmagnetic transition, and which therefore react very sensitively
to changes in the local geometry. The results indicate that high spin states in
manganese-doped silicon could be stabilized by an appropriate lattice
expansion
More than skin deep: Functional genomic basis for resistance to Amphibian Chytridiomycosis
The amphibian-killing chytrid fungus Batrachochytriumdendrobatidis (Bd) is one of themost generalist pathogens known, capable of
infecting hundreds of species globally and causing widespread population declines and extinctions. However, some host species are
seemingly unaffected by Bd, tolerating or clearing infections without clinical signs of disease. Variation in host immune responses is
commonly evoked for these resistant or tolerant species, yet to date,we have nodirect comparisonof amphibian species responses to
infection at the level of gene expression. In this study,we challenged four CentralAmerican frog species that vary in Bd susceptibility,
with a sympatric virulent strain of the pathogen. We compared skin and spleen orthologous gene expression using differential
expression tests and coexpression gene network analyses.Wefound that resistant species have reduced skin inflammatory responses
andincreased expressionofgenes involved inskin integrity. Incontrast, onlyhighly susceptible species exhibited suppressionof splenic
T-cell genes. We conclude that resistance to chytridiomycosis may be related to a species’ ability to escape the immunosuppressive
activity of the fungus. Moreover, our results indicate that within-species differences in splenic proteolytic enzyme gene expression
may contribute to intraspecific variation in survival. This first comparison of amphibian functional immunogenomic architecture in
response to Bd provides insights into key genetic mechanisms underlying variation in disease outcomes among amphibian species
TDP-43 Mediated Blood-Brain Barrier Permeability and Leukocyte Infiltration Promote Neurodegeneration in a Low-Grade Systemic Inflammation Mouse Model
BACKGROUND: Neuronal cytoplasmic inclusions containing TAR DNA-binding protein 43 (TDP-43) are a neuropathological feature of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer\u27s Disease (AD). Emerging evidence also indicates that systemic inflammation may be a contributor to the pathology progression of these neurodegenerative diseases.
METHODS: To investigate the role of systemic inflammation in the progression of neuronal TDP-43 pathology, AAV9 particles driven by the UCHL1 promoter were delivered to the frontal cortex of wild-type aged mice via intracranial injections to overexpress TDP-43 or green fluorescent protein (GFP) in corticospinal motor neurons. Animals were then subjected to a low-dose (500 μg/kg) intraperitoneal E. coli lipopolysaccharide (LPS) administration challenge for 2 weeks to mimic a chronically altered low-grade systemic inflammatory state. Mice were then subjected to neurobehavioral studies, followed by biochemical and immunohistochemical analyses of the brain tissue.
RESULTS: In the present study, we report that elevated neuronal TDP-43 levels induced microglial and astrocytic activation in the cortex of injected mice followed by increased RANTES signaling. Moreover, overexpression of TDP-43 exerted abundant mouse immunoglobulin G (IgG), CD3, and CD4+ T cell infiltration as well as endothelial and pericyte activation suggesting increased blood-brain barrier permeability. The BBB permeability in TDP-43 overexpressing brains yielded the frontal cortex vulnerable to the systemic inflammatory response following LPS treatment, leading to marked neutrophil infiltration, neuronal loss, reduced synaptosome-associated protein 25 (SNAP-25) levels, and behavioral impairments in the radial arm water maze (RAWM) task.
CONCLUSIONS: These results reveal a novel role for TDP-43 in BBB permeability and leukocyte recruitment, indicating complex intermolecular interactions between an altered systemic inflammatory state and pathologically prone TDP-43 protein to promote disease progression
Mn-Acetate Complexes Studied as Single Molecules
The phenomenon of single molecule magnet (SMM) behavior of mixed valent Mn12 coordination clusters of general formula [MnMnO(RCOO)(HO)] had been exemplified by bulk samples of the archetypal [MnMnO(CHCOO)(HO)] (4) molecule, and the molecular origin of the observed magnetic behavior has found support from extensive studies on the Mn12 system within crystalline material or on molecules attached to a variety of surfaces. Here we report the magnetic signature of the isolated cationic species [MnO(CHCOO)(CHCN)] (1) by gas phase X-ray Magnetic Circular Dichroism (XMCD) spectroscopy, and we find it closely resembling that of the corresponding bulk samples. Furthermore, we report broken symmetry DFT calculations of spin densities and single ion tensors of the isolated, optimized complexes [MnO(CHCOO)(CHCN)] (1), [[MnO(CHCOO)] (2), [MnO(CHCOO)(HO)] (3), and the complex in bulk geometry [MnMnO(CHCOO)(HO)] (5). The found magnetic fingerprints – experiment and theory alike – are of a remarkable robustness: The Mn core bears almost no magnetic anisotropy while the surrounding MnIII8 ring is highly anisotropic. These signatures are truly intrinsic properties of the Mn core scaffold within all of these complexes and largely void of the environment. This likely holds irrespective of bulk packing effects
Xpert MTB/RIF Assay Shows Faster Clearance of Mycobacterium tuberculosis DNA with Higher Levels of Rifapentine Exposure.
The Xpert MTB/RIF assay is both sensitive and specific as a diagnostic test. Xpert also reports quantitative output in cycle threshold (CT) values, which may provide a dynamic measure of sputum bacillary burden when used longitudinally. We evaluated the relationship between Xpert CT trajectory and drug exposure during tuberculosis (TB) treatment to assess the potential utility of Xpert CT for treatment monitoring. We obtained serial sputum samples from patients with smear-positive pulmonary TB who were consecutively enrolled at 10 international clinical trial sites participating in study 29X, a CDC-sponsored Tuberculosis Trials Consortium study evaluating the tolerability, safety, and antimicrobial activity of rifapentine at daily doses of up to 20 mg/kg of body weight. Xpert was performed at weeks 0, 2, 4, 6, 8, and 12. Longitudinal CT data were modeled using a nonlinear mixed effects model in relation to rifapentine exposure (area under the concentration-time curve [AUC]). The rate of change of CT was higher in subjects receiving rifapentine than in subjects receiving standard-dose rifampin. Moreover, rifapentine exposure, but not assigned dose, was significantly associated with rate of change in CT (P = 0.02). The estimated increase in CT slope for every additional 100 μg · h/ml of rifapentine drug exposure (as measured by AUC) was 0.11 CT/week (95% confidence interval [CI], 0.05 to 0.17). Increasing rifapentine exposure is associated with a higher rate of change of Xpert CT, indicating faster clearance of Mycobacterium tuberculosis DNA. These data suggest that the quantitative outputs of the Xpert MTB/RIF assay may be useful as a dynamic measure of TB treatment response
Biogeographical patterns and speciation of the genus Pinguicula (Lentibulariaceae) inferred by phylogenetic analyses
Earlier phylogenetic studies in the genus Pinguicua (Lentibulariaceae) suggested that the species within a geographical region was rather monophyletic, although the sampling was limited or was restricted to specific regions. Those results conflicted with the floral morphology-based classification, which has been widely accepted to date. In the current study, one nuclear ribosomal DNA (internal transcribed spacer; ITS) and two regions of chloroplast DNA (matK and rpl32-trnL), from up to ca. 80% of the taxa in the genus Pinguicula, covering all three subgenera, were sequenced to demonstrate the inconsistency and explore a possible evolutionary history of the genus. Some incongruence was observed between nuclear and chloroplast topologies and the results from each of the three DNA analyses conflicted with the morphology-based subgeneric divisions. Both the ITS tree and network, however, corresponded with the biogeographical patterns of the genus supported by life-forms (winter rosette or hibernaculum formation) and basic chromosome numbers (haploidy). The dormant strategy evolved in a specific geographical region is a phylogenetic constraint and a synapomorphic characteristic within a lineage. Therefore, the results denied the idea that the Mexican group, morphologically divided into the three subgenera, independently acquired winter rosette formations. Topological incongruence among the trees or reticulations, indicated by parallel edges in phylogenetic networks, implied that some taxa originated by introgressive hybridisation. Although there are exceptions, species within the same geographical region arose from a common ancestor. Therefore, the classification by the floral characteristics is rather unreliable. The results obtained from this study suggest that evolution within the genus Pinguicula has involved; 1) ancient expansions to geographical regions with gene flow and subsequent vicariance with genetic drift, 2) acquirement of a common dormant strategy within a specific lineage to adapt a local climate (i.e., synapomorphic characteristic), 3) recent speciation in a short time span linked to introgressive hybridisation or multiplying the ploidy level (i.e., divergence), and 4) parallel evolution in floral traits among lineages found in different geographical regions (i.e., convergence). As such, the floral morphology masks and obscures the phylogenetic relationships among species in the genus
The spatial analysis of biological interactions:Morphological variation responding to the co-occurrence of competitors and resources
By sharing geographic space, species are forced to interact with one another and the contribution of this process to evolutionary and ecological patterns of individual species is not fully understood. At the same time, species turnover makes that species composition varies from one area to another, so the analysis of biological interaction cannot be uncoupled from the spatial context. This is particularly important for clades that show high degree of specialization such as hummingbirds, where any variation in biotic pressures might lead to changes in morphology. Here, we describe the influence of biological interactions on the morphology of Hylocharis leucotis by simultaneously considering potential competition and diet resources. We characterized the extent of local potential competition and local available floral resources by correlating two measurements of hummingbird diversity, floral resources and the size of morphological space of H. leucotis along its geographic distribution. We found that H. leucotis shows an important morphological variability across its range and two groups can be recognized. Surprisingly, morphological variation is not always linked to local hummingbird richness or the phylogenetic similarity of. Only in the southern part of its distribution, H. leucotis is morphologically more variable in those communities where it coexist with closely related hummingbird species. We also found that morphological variation in H. leucotis is independent from the availability of floral resources. Our results suggest that abiotic factors might be responsible for morphological differences across populations in Hylocharis leucotis being biological interactions of minor importance.</p
Amphibianâ killing chytrid in Brazil comprises both locally endemic and globally expanding populations
Chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), is the emerging infectious disease implicated in recent population declines and extinctions of amphibian species worldwide. Bd strains from regions of diseaseâ associated amphibian decline to date have all belonged to a single, hypervirulent clonal genotype (Bdâ GPL). However, earlier studies in the Atlantic Forest of southeastern Brazil detected a novel, putatively enzootic lineage (Bdâ Brazil), and indicated hybridization between Bdâ GPL and Bdâ Brazil. Here, we characterize the spatial distribution and population history of these sympatric lineages in the Brazilian Atlantic Forest. To investigate the genetic structure of Bd in this region, we collected and genotyped Bd strains along a 2400â km transect of the Atlantic Forest. Bdâ Brazil genotypes were restricted to a narrow geographic range in the southern Atlantic Forest, while Bdâ GPL strains were widespread and largely geographically unstructured. Bd population genetics in this region support the hypothesis that the recently discovered Brazilian lineage is enzootic in the Atlantic Forest of Brazil and that Bdâ GPL is a more recently expanded invasive. We collected additional hybrid isolates that demonstrate the recurrence of hybridization between panzootic and enzootic lineages, thereby confirming the existence of a hybrid zone in the Serra da Graciosa mountain range of Paraná State. Our field observations suggest that Bdâ GPL may be more infective towards native Brazilian amphibians, and potentially more effective at dispersing across a fragmented landscape. We also provide further evidence of pathogen translocations mediated by the Brazilian ranaculture industry with implications for regulations and policies on global amphibian trade.See also the Perspective by Ghosh and FisherPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/122445/1/mec13599.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/122445/2/mec13599_am.pd
Planetary Candidates Observed by Kepler. VIII. A Fully Automated Catalog With Measured Completeness and Reliability Based on Data Release 25
We present the Kepler Object of Interest (KOI) catalog of transiting
exoplanets based on searching four years of Kepler time series photometry (Data
Release 25, Q1-Q17). The catalog contains 8054 KOIs of which 4034 are planet
candidates with periods between 0.25 and 632 days. Of these candidates, 219 are
new and include two in multi-planet systems (KOI-82.06 and KOI-2926.05), and
ten high-reliability, terrestrial-size, habitable zone candidates. This catalog
was created using a tool called the Robovetter which automatically vets the
DR25 Threshold Crossing Events (TCEs, Twicken et al. 2016). The Robovetter also
vetted simulated data sets and measured how well it was able to separate TCEs
caused by noise from those caused by low signal-to-noise transits. We discusses
the Robovetter and the metrics it uses to sort TCEs. For orbital periods less
than 100 days the Robovetter completeness (the fraction of simulated transits
that are determined to be planet candidates) across all observed stars is
greater than 85%. For the same period range, the catalog reliability (the
fraction of candidates that are not due to instrumental or stellar noise) is
greater than 98%. However, for low signal-to-noise candidates between 200 and
500 days around FGK dwarf stars, the Robovetter is 76.7% complete and the
catalog is 50.5% reliable. The KOI catalog, the transit fits and all of the
simulated data used to characterize this catalog are available at the NASA
Exoplanet Archive.Comment: 61 pages, 23 Figures, 9 Tables, Accepted to The Astrophysical Journal
Supplement Serie
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