50 research outputs found
Limited genetic variation and structure in softshell clams (Mya arenaria) across their native and introduced range
Author Posting. © Springer, 2009. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Conservation Genetics 10 (2009): 803-814, doi:10.1007/s10592-008-9641-y.To offset declines in commercial landings of the softshell clam, Mya arenaria, resource
managers are engaged in extensive stocking of seed clams throughout its range in the
northwest Atlantic. Because a mixture of native and introduced stocks can disrupt locally
adapted genotypes, we investigated genetic structure in M. arenaria populations across
its current distribution to test for patterns of regional differentiation. We sequenced
mitochondrial cytochrome oxidase I (COI) for a total of 212 individuals from 12 sites in
the northwest Atlantic (NW Atlantic), as well as two introduced sites, the northeast
Pacific (NE Pacific) and the North Sea and Europe (NS Europe). Populations exhibited
extremely low genetic variation, with one haplotype dominating (65-100%) at all sites
sampled. Despite being introduced in the last 150-400 years, both NE Pacific and NS
Europe populations had higher diversity measures than those in the NW Atlantic and both
contained private haplotypes at frequencies of 10% to 27% consistent with their
geographic isolation. While significant genetic structure (FST = 0.159, p<0.001) was
observed between NW Atlantic and NS Europe, there was no evidence for genetic
structure across the pronounced environmental clines of the NW Atlantic. Reduced
genetic diversity in mtDNA combined with previous studies reporting reduced genetic
diversity in nuclear markers strongly suggests a recent population expansion in the NW
Atlantic, a pattern that may result from the retreat of ice sheets during Pleistocene glacial
periods. Lack of genetic diversity and regional genetic differentiation suggests that
present management strategies for the commercially important softshell clam are unlikely
to have a significant impact on the regional distribution of genetic variation, although the
possibility of disrupting locally adapted stocks cannot be excluded.This work was supported by NSF grants OCE-0326734 and OCE-0215905 to L.
Mullineaux and OCE- 0349177 (Biological Oceanography) to PHB
Shear wave velocity prediction using seismic attributes and well log data
Formation’s properties can be estimated indirectly using joint analysis of compressional and shear wave velocities. Shear wave data isnot usually acquired during well logging, which is most likely for costsaving purposes. Even if shear data is available, the logging programs provide only sparsely sampled one-dimensional measurements: this informationis inadequate to estimate reservoir rock properties. Thus, if the shear wave data can be obtained using seismic methods, the results can be used across the field to estimate reservoir properties. The aim of this paper is to use seismic attributes for prediction of shear wave velocity in a field located in southern part of Iran. Independent component analysis(ICA) was used to select the most relevant attributes to shear velocity data. Considering the nonlinear relationship between seismic attributes and shear wave velocity, multi-layer feed forward neural network was used for prediction of shear wave velocity and promising results were presented
Age-Dependent Maturation of Toll-Like Receptor-Mediated Cytokine Responses in Gambian Infants
The global burden of neonatal and infant mortality due to infection is
staggering, particularly in resource-poor settings. Early childhood vaccination
is one of the major interventions that can reduce this burden, but there are
specific limitations to inducing effective immunity in early life, including
impaired neonatal leukocyte production of Th1-polarizing cytokines to many
stimuli. Characterizing the ontogeny of Toll-like receptor (TLR)-mediated innate
immune responses in infants may shed light on susceptibility to infection in
this vulnerable age group, and provide insights into TLR agonists as candidate
adjuvants for improved neonatal vaccines. As little is known about the leukocyte
responses of infants in resource-poor settings, we characterized production of
Th1-, Th2-, and anti-inflammatory- cytokines in response to agonists of TLRs 1-9
in whole blood from 120 Gambian infants ranging from newborns (cord blood) to 12
months of age. Most of the TLR agonists induced TNFα, IL-1β, IL-6, and
IL-10 in cord blood. The greatest TNFα responses were observed for TLR4, -5,
and -8 agonists, the highest being the thiazoloquinoline CLO75 (TLR7/8) that
also uniquely induced cord blood IFNγ production. For most agonists,
TLR-mediated TNFα and IFNγ responses increased from birth to 1 month of
age. TLR8 agonists also induced the greatest production of the Th1-polarizing
cytokines TNFα and IFNγ throughout the first year of life, although the
relative responses to the single TLR8 agonist and the combined TLR7/8 agonist
changed with age. In contrast, IL-1β, IL-6, and IL-10 responses to most
agonists were robust at birth and remained stable through 12 months of age.
These observations provide fresh insights into the ontogeny of innate immunity
in African children, and may inform development of age-specific adjuvanted
vaccine formulations important for global health
Aeroallergen-induced IL-33 predisposes to respiratory virus–induced asthma by dampening antiviral immunity
Background Frequent viral lower respiratory infections in early life are an independent risk factor for asthma onset. This risk and the development of persistent asthma are significantly greater in children who later become sensitized. Objective We sought to elucidate the pathogenic processes that underlie the synergistic interplay between allergen exposures and viral infections. Methods Mice were inoculated with a murine-specific Pneumovirus species (pneumonia virus of mice [PVM]) and exposed to low-dose cockroach extract (CRE) in early and later life, and airway inflammation, remodeling, and hyperreactivity assessed. Mice were treated with anti–IL-33 or apyrase to neutralize or block IL-33 release. Results PVM infection or CRE exposure alone did not induce disease, whereas PVM/CRE coexposure acted synergistically to induce the hallmark features of asthma. CRE exposure during viral infection in early life induced a biphasic IL-33 response and impaired IFN-α and IFN-λ production, which in turn increased epithelial viral burden, airway smooth muscle growth, and type 2 inflammation. These features were ameliorated when CRE-induced IL-33 release was blocked or neutralized, whereas substitution of CRE with exogenous IL-33 recapitulated the phenotype observed in PVM/CRE-coexposed mice. Mechanistically, IL-33 downregulated viperin and interferon regulatory factor 7 gene expression and rapidly degraded IL-1 receptor–associated kinase 1 expression in plasmacytoid dendritic cells both in\ua0vivo and in\ua0vitro, leading to Toll-like receptor 7 hyporesponsiveness and impaired IFN-α production. Conclusion We identified a hitherto unrecognized function of IL-33 as a potent suppressor of innate antiviral immunity and demonstrate that IL-33 contributes significantly to the synergistic interplay between respiratory virus and allergen exposures in the onset and progression of asthma
HMGB1 amplifies ILC2-induced type-2 inflammation and airway smooth muscle remodelling.
Type-2 immunity elicits tissue repair and homeostasis, however dysregulated type-2 responses cause aberrant tissue remodelling, as observed in asthma. Severe respiratory viral infections in infancy predispose to later asthma, however, the processes that mediate tissue damage-induced type-2 inflammation and the origins of airway remodelling remain ill-defined. Here, using a preclinical mouse model of viral bronchiolitis, we find that increased epithelial and mesenchymal high-mobility group box 1 (HMGB1) expression is associated with increased numbers of IL-13-producing type-2 innate lymphoid cell (ILC2s) and the expansion of the airway smooth muscle (ASM) layer. Anti-HMGB1 ablated lung ILC2 numbers and ASM growth in vivo, and inhibited ILC2-mediated ASM cell proliferation in a co-culture model. Furthermore, we identified that HMGB1/RAGE (receptor for advanced glycation endproducts) signalling mediates an ILC2-intrinsic IL-13 auto-amplification loop. In summary, therapeutic targeting of the HMGB1/RAGE signalling axis may act as a novel asthma preventative by dampening ILC2-mediated type-2 inflammation and associated ASM remodelling
Plasmacytoid dendritic cells protect from viral bronchiolitis and asthma through semaphorin 4a-mediated T reg expansion
Respiratory syncytial virus–bronchiolitis is a major independent risk factor for subsequent asthma, but the causal mechanisms remain obscure. We identified that transient plasmacytoid dendritic cell (pDC) depletion during primary Pneumovirus infection alone predisposed to severe bronchiolitis in early life and subsequent asthma in later life after reinfection. pDC depletion ablated interferon production and increased viral load; however, the heightened immunopathology and susceptibility to subsequent asthma stemmed from a failure to expand functional neuropilin-1+ regulatory T (T reg) cells in the absence of pDC-derived semaphorin 4a (Sema4a). In adult mice, pDC depletion predisposed to severe bronchiolitis only after antibiotic treatment. Consistent with a protective role for the microbiome, treatment of pDC-depleted neonates with the microbial-derived metabolite propionate promoted Sema4a-dependent T reg cell expansion, ameliorating both diseases. In children with viral bronchiolitis, nasal propionate levels were decreased and correlated with an IL-6high/IL-10low microenvironment. We highlight a common but age-related Sema4a-mediated pathway by which pDCs and microbial colonization induce T reg cell expansion to protect against severe bronchiolitis and subsequent asthma.</jats:p
Genomic insights into the host specific adaptation of the Pneumocystis genus
Pneumocystis jirovecii, the fungal agent of human Pneumocystis pneumonia, is closely related to macaque Pneumocystis. Little is known about other Pneumocystis species in distantly related mammals, none of which are capable of establishing infection in humans. The molecular basis of host specificity in Pneumocystis remains unknown as experiments are limited due to an inability to culture any species in vitro. To explore Pneumocystis evolutionary adaptations, we have sequenced the genomes of species infecting macaques, rabbits, dogs and rats and compared them to available genomes of species infecting humans, mice and rats. Complete whole genome sequence data enables analysis and robust phylogeny, identification of important genetic features of the host adaptation, and estimation of speciation timing relative to the rise of their mammalian hosts. Our data reveals insights into the evolution of P. jirovecii, the sole member of the genus able to infect humans.http://deepblue.lib.umich.edu/bitstream/2027.42/174884/2/Genomic insights into the host specific adaptation of the Pneumocystis genus.pdfPublished versio