1,152 research outputs found
Decimation by sea star wasting disease and rapid genetic change in a keystone species, \u3cem\u3ePisaster ochraceus\u3c/em\u3e
Standing genetic variation enables or restricts a population’s capacity to respond to changing conditions, including the extreme disturbances expected to increase in frequency and intensity with continuing anthropogenic climate change. However, we know little about how populations might respond to extreme events with rapid genetic shifts, or how population dynamics may influence and be influenced by population genomic change. We use a range-wide epizootic, sea star wasting disease, that onset in mid-2013 and caused mass mortality in Pisaster ochraceus to explore how a keystone marine species responded to an extreme perturbation. We integrated field surveys with restriction site-associated DNA sequencing data to (i) describe the population dynamics of mortality and recovery, and (ii) compare allele frequencies in mature P. ochraceus before the disease outbreak with allele frequencies in adults and new juveniles after the outbreak, to identify whether selection may have occurred. We found P. ochraceus suffered 81% mortality in the study region between 2012 and 2015, and experienced a concurrent 74-fold increase in recruitment beginning in late 2013. Comparison of pre- and postoutbreak adults revealed significant allele frequency changes at three loci, which showed consistent changes across the large majority of locations. Allele frequency shifts in juvenile P. ochraceus (spawned from premortality adults) were consistent with those seen in adult survivors. Such parallel shifts suggest detectable signals of selection and highlight the potential for persistence of this change in subsequent generations, which may influence the resilience of this keystone species to future outbreaks
Direct and indirect effects of retinoic acid on human Th2 cytokine and chemokine expression by human T lymphocytes
BACKGROUND: Vitamin A (VA) deficiency induces a type 1 cytokine response and exogenously provided retinoids can induce a type 2 cytokine response both in vitro and in vivo. The precise mechanism(s) involved in this phenotypic switch are inconsistent and have been poorly characterized in humans. In an effort to determine if retinoids are capable of inducing Th2 cytokine responses in human T cell cultures, we stimulated human PBMCs with immobilized anti-CD3 mAb in the presence or absence of all-trans retinoic acid (ATRA) or 9-cis-RA. RESULTS: Stimulation of human PBMCs and purified T cells with ATRA and 9-cis-RA increased mRNA and protein levels of IL-4, IL-5, and IL-13 and decreased levels of IFN-γ, IL-2, IL-12p70 and TNF-α upon activation with anti-CD3 and/or anti-CD28 mAbs. These effects were dose-dependent and evident as early as 12 hr post stimulation. Real time RT-PCR analysis revealed a dampened expression of the Th1-associated gene, T-bet, and a time-dependent increase in the mRNA for the Th2-associated genes, GATA-3, c-MAF and STAT6, upon treatment with ATRA. Besides Th1 and Th2 cytokines, a number of additional proinflammatory and regulatory cytokines including several chemokines were also differentially regulated by ATRA treatment. CONCLUSION: These data provide strong evidence for multiple inductive roles for retinoids in the development of human type-2 cytokine responses
Frontiers of Biogeography:Taking its place as a journal of choice for the publication of high quality biogeographical research articles
Through this editorial we seek your support and engagement as authors, readers and reviewers as we take the next steps in developing Frontiers of Biogeography as a leading international journal of biogeography and related subdisciplines. Here we make the case for submitting your next contribution to this journal: affordable, gold libre, open access, with the support of a disciplinarily-informed editorial and review team, which returns benefits to the biogeography community.Peer Reviewe
Layered architecture for quantum computing
We develop a layered quantum computer architecture, which is a systematic
framework for tackling the individual challenges of developing a quantum
computer while constructing a cohesive device design. We discuss many of the
prominent techniques for implementing circuit-model quantum computing and
introduce several new methods, with an emphasis on employing surface code
quantum error correction. In doing so, we propose a new quantum computer
architecture based on optical control of quantum dots. The timescales of
physical hardware operations and logical, error-corrected quantum gates differ
by several orders of magnitude. By dividing functionality into layers, we can
design and analyze subsystems independently, demonstrating the value of our
layered architectural approach. Using this concrete hardware platform, we
provide resource analysis for executing fault-tolerant quantum algorithms for
integer factoring and quantum simulation, finding that the quantum dot
architecture we study could solve such problems on the timescale of days.Comment: 27 pages, 20 figure
Localization and chiral symmetry in 2+1 flavor domain wall QCD
We present results for the dependence of the residual mass of domain wall
fermions (DWF) on the size of the fifth dimension and its relation to the
density and localization properties of low-lying eigenvectors of the
corresponding hermitian Wilson Dirac operator relevant to simulations of 2+1
flavor domain wall QCD. Using the DBW2 and Iwasaki gauge actions, we generate
ensembles of configurations with a space-time volume and an
extent of 8 in the fifth dimension for the sea quarks. We demonstrate the
existence of a regime where the degree of locality, the size of chiral symmetry
breaking and the rate of topology change can be acceptable for inverse lattice
spacings GeV.Comment: 59 Pages, 23 figures, 1 MPG linke
Comparative simulation study of colloidal gels and glasses
Using computer simulations, we identify the mechanisms causing aggregation
and structural arrest of colloidal suspensions interacting with a short-ranged
attraction at moderate and high densities. Two different non-ergodicity
transitions are observed. As the density is increased, a glass transition takes
place, driven by excluded volume effects. In contrast, at moderate densities,
gelation is approached as the strength of the attraction increases. At high
density and interaction strength, both transitions merge, and a logarithmic
decay in the correlation function is observed. All of these features are
correctly predicted by mode coupling theory
Development of intraspecific size variation in black coucals, white‐browed coucals and ruffs from hatching to fledging
Most studies on sexual size dimorphism address proximate and functional questions related to adults, but sexual size dimorphism usually develops during ontogeny and developmental trajectories of sexual size dimorphism are poorly understood. We studied three bird species with variation in adult sexual size dimorphism: black coucals (females 69% heavier than males), white‐browed coucals (females 13% heavier than males) and ruffs (males 70% heavier than females). Using a flexible Bayesian generalized additive model framework (GAMM), we examined when and how sexual size dimorphism developed in body mass, tarsus length and bill length from hatching until fledging. In ruffs, we additionally examined the development of intrasexual size variation among three morphs (Independents, Satellites and Faeders), which creates another level of variation in adult size of males and females. We found that 27–100% of the adult inter‐ and intrasexual size variation developed until fledging although none of the species completed growth during the observational period. In general, the larger sex/morph grew more quickly and reached its maximal absolute growth rate later than the smaller sex/morph. However, when the daily increase in body mass was modelled as a proportion, growth patterns were synchronized between and within sexes. Growth broadly followed sigmoidal asymptotic models, however only with the flexible GAMM approach, residual distributions were homogeneous over the entire observation periods. These results provide a platform for future studies to relate variation in growth to selective pressures and proximate mechanisms in these three species, and they highlight the advantage of using a flexible model approach for examining growth variation during ontogeny
Structure-based design and synthesis of antiparasitic pyrrolopyrimidines targeting pteridine reductase 1
The treatment of Human African Trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important and pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp. has been identified as a candidate target and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 from T. brucei (J. Med. Chem. 2010, 53, 221-229). In this study, 61 new pyrrolo[2,3-d]pyrimidines have been prepared, designed with input from new crystal structures of 23 of these compounds complexed with PTR1, and evaluated in screens for enzyme inhibitory activity against PTR1 and in vitro antitrypanosomal activity. 8 compounds were sufficiently active in both screens to take forward to in vivo evaluation. Thus although evidence for trypanocidal activity in a stage I disease model in mice was obtained, the compounds were too toxic to mice for further development
Rationale for Stereotactic Body Radiation Therapy in Treating Patients with Oligometastatic Hormone-Naïve Prostate Cancer
Despite advances in treatment for metastatic prostate cancer, patients eventually progress to castrate-resistant disease and ultimately succumb to their cancer. Androgen deprivation therapy (ADT) is the standard treatment for metastatic prostate cancer and has been shown to improve median time to progression and median survival time. Research suggests that castrate-resistant clones may be present early in the disease process prior to the initiation of ADT. These clones are not susceptible to ADT and may even flourish when androgen-responsive clones are depleted. Stereotactic body radiation therapy (SBRT) is a safe and efficacious method of treating clinically localized prostate cancer and metastases. In patients with a limited number of metastatic sites, SBRT may have a role in eliminating castrate-resistant clones and possibly delaying progression to castrate-resistant disease
Supersymmetric Higgs Yukawa Couplings to Bottom Quarks at next-to-next-to-leading Order
The effective bottom Yukawa couplings are analyzed for the minimal
supersymmetric extension of the Standard Model at two-loop accuracy within
SUSY-QCD. They include the resummation of the dominant corrections for large
values of tg(beta). In particular the two-loop SUSY-QCD corrections to the
leading SUSY-QCD and top-induced SUSY-electroweak contributions are addressed.
The residual theoretical uncertainties range at the per-cent level.Comment: 25 pages, 9 figures, added comments and references, typos corrected,
results unchanged, published versio
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