DNA immunization circumvents deficient induction of T helper type 1 and cytotoxic T lymphocyte responses in neonates and during early life

The relative deficiency of T helper type 1 (Th1) and cytotoxic T lymphocyte (CTL) responses in early life is associated with an increased susceptibility to infections by intracellular microorganisms. This is likely to reflect a preferential polarization of immature CD4 T cells toward a Th2 rather than a Th1 pattern upon immunization with conventional vaccines. In this report, it is shown that a single immunization within the first week of life with DNA plasmids encoding viral (measles virus hemagglutinin, Sendai virus nucleoprotein) or bacterial (C fragment of tetanus toxin) vaccine antigens can induce adult-like Th1 or mixed Th1/Th2 responses indicated by production of IgG2a vaccine-specific antibodies and preferential secretion of interferon-γ (IFN-γ) compared with interleukin (IL)-5 by antigen-specific T cells, as well as significant CTL responses. However, in spite of this potent Th1-driving capacity, subsequent DNA immunization was not capable of reverting the Th2-biased responses induced after early priming with a recombinant measles canarypox vector. Thus, DNA vaccination represents a novel strategy capable of inducing Th1 or mixed Th1/Th2 and CTL responses in neonates and early life, providing it is performed prior to exposure to Th2-driving conventional vaccine antigens.

The compensatory potential of increased immigration following intensive American mink population control is diluted by male-biased dispersal

Acknowledgments This research was funded by NERC Grants NE/J01396X/1; NE/E006434/1 to XL. Y. M. was funded by a Marie Curie FP7-PEOPLE-2011-IEF 300288. We profusely thank the Scottish Mink Initiative, staff, funders and multiple mink volunteers for the continued effort, samples and enthusiasm. The Scottish Water Vole Conservation Project was funded by The Tubney Charitable trust, Scottish Natural Heritage, the Cairngorms National Park Authority and the People’s Trust for Endangered Species. We also thank the Associate Editor and two anonymous referees for their thoughtful reviews.

Gene dosage and stochastic effects determine the severity and direction of uniparental ribosomal RNA gene silencing (nucleolar dominance) in Arabidopsis allopolyploids

Nucleolar dominance is an epigenetic phenomenon in which one parental set of ribosomal RNA (rRNA) genes is silenced in an interspecific hybrid. In natural Arabidopsis suecica, an allotetraploid (amphidiploid) hybrid of Arabidopsis thaliana and Cardaminopsis arenosa, the A. thaliana rRNA genes are repressed. Interestingly, A. thaliana rRNA gene silencing is variable in synthetic Arabidopsis suecica F1 hybrids. Two generations are needed for A. thaliana rRNA genes to be silenced in all lines, revealing a species-biased direction but stochastic onset to nucleolar dominance. Backcrossing synthetic A. suecica to tetraploid A. thaliana yielded progeny with active A. thaliana rRNA genes and, in some cases, silenced C. arenosa rRNA genes, showing that the direction of dominance can be switched. The hypothesis that naturally dominant rRNA genes have a superior binding affinity for a limiting transcription factor is inconsistent with dominance switching. Inactivation of a species-specific transcription factor is argued against by showing that A. thaliana and C. arenosa rRNA genes can be expressed transiently in the other species. Transfected A. thaliana genes are also active in A. suecica protoplasts in which chromosomal A. thaliana genes are repressed. Collectively, these data suggest that nucleolar dominance is a chromosomal phenomenon that results in coordinate or cooperative silencing of rRNA genes.

Pseudoknots in prion protein mRNAs confirmed by comparative sequence analysis and pattern searching

The human prion gene contains five copies of a 24 nt repeat that is highly conserved among species. An analysis of folding free energies of the human prion mRNA, in particular in the repeat region, suggested biased codon selection and the presence of RNA patterns. In particular, pseudoknots, similar to the one predicted by Wills in the human prion mRNA, were identified in the repeat region of all available prion mRNAs available in GenBank, but not those of birds and the red slider turtle. An alignment of these mRNAs, which share low sequence homology, shows several co-variations that maintain the pseudoknot pattern. The presence of pseudoknots in yeast Sup35p and Rnq1 suggests acquisition in the prokaryotic era. Computer generated three-dimensional structures of the human prion pseudoknot highlight protein and RNA interaction domains, which suggest a possible effect in prion protein translation. The role of pseudoknots in prion diseases is discussed as individuals with extra copies of the 24 nt repeat develop the familial form of Creutzfeldt–Jakob disease.

Effects of passage history and sampling bias on phylogenetic reconstruction of human influenza A evolution

In this paper we determine the extent to which host-mediated mutations and a known sampling bias affect evolutionary studies of human influenza A. Previous phylogenetic reconstruction of influenza A (H3N2) evolution using the hemagglutinin gene revealed an excess of nonsilent substitutions assigned to the terminal branches of the tree. We investigate two hypotheses to explain this observation. The first hypothesis is that the excess reflects mutations that were either not present or were at low frequency in the viral sample isolated from its human host, and that these mutations increased in frequency during passage of the virus in embryonated eggs. A set of 22 codons known to undergo such “host-mediated” mutations showed a significant excess of mutations assigned to branches attaching sequences from egg-cultured (as opposed to cell-cultured) isolates to the tree. Our second hypothesis is that the remaining excess results from sampling bias. Influenza surveillance is purposefully biased toward sequencing antigenically dissimilar strains in an effort to identify new variants that may signal the need to update the vaccine. This bias produces an excess of mutations assigned to terminal branches simply because an isolate with no close relatives is by definition attached to the tree by a relatively long branch. Simulations show that the magnitude of excess mutations we observed in the hemagglutinin tree is consistent with expectations based on our sampling protocol. Sampling bias does not affect inferences about evolution drawn from phylogenetic analyses. However, if possible, the excess caused by host-mediated mutations should be removed from studies of the evolution of influenza viruses as they replicate in their human hosts.

A distribution of tumor size at detection and its limiting form.

A distribution of tumor size at detection is derived within the framework of a mechanistic model of carcinogenesis with the object of estimating biologically meaningful parameters of tumor latency. Its limiting form appears to be a generalization of the distribution that arises in the length-biased sampling from stationary point processes. The model renders the associated estimation problems tractable. The usefulness of the proposed approach is illustrated with an application to clinical data on premenopausal breast cancer.

Recombinational repair of gaps in DNA is asymmetric in Ustilago maydis and can be explained by a migrating D-loop model.

Recombinational repair of double-stranded DNA gaps was investigated in Ustilago maydis. The experimental system was designed for analysis of repair of an autonomously replicating plasmid containing a cloned gene disabled by an internal deletion. It was discovered that crossing over rarely accompanied gap repair. The strong bias against crossing over was observed in three different genes regardless of gap size. These results indicate that gap repair in U. maydis is unlikely to proceed by the mechanism envisioned in the double-stranded break repair model of recombination, which was developed to account for recombination in Saccharomyces cerevisiae. Experiments aimed at exploring processing of DNA ends were performed to gain understanding of the mechanism responsible for the observed bias. A heterologous insert placed within a gap in the coding sequence of two different marker genes strongly inhibited repair if the DNA was cleaved at the promoter-proximal junction joining the insert and coding sequence but had little effect on repair if the DNA was cleaved at the promoter-distal junction. Gene conversion of plasmid restriction fragment length polymorphism markers engineered in sequences flanking both sides of a gap accompanied repair but was directionally biased. These results are interpreted to mean that the DNA ends flanking a gap are subject to different types of processing. A model featuring a single migrating D-loop is proposed to explain the bias in gap repair outcome based on the observed asymmetry in processing the DNA ends.

Complete congruence between gene diversity estimates derived from genotypic data at enzyme and random amplified polymorphic DNA loci in black spruce.

Controversy still exists over the adaptive nature of variation of enzyme loci. In conifers, random amplified polymorphic DNAs (RAPDs) represent a class of marker loci that is unlikely to fall within or be strongly linked to coding DNA. We have compared the genetic diversity in natural populations of black spruce [Picea mariana (Mill.) B.S.P.] using genotypic data at allozyme loci and RAPD loci as well as phenotypic data from inferred RAPD fingerprints. The genotypic data for both allozymes and RAPDs were obtained from at least six haploid megagametophytes for each of 75 sexually mature individuals distributed in five populations. Heterozygosities and population fixation indices were in complete agreement between allozyme loci and RAPD loci. In black spruce, it is more likely that the similar levels of variation detected at both enzyme and RAPD loci are due to such evolutionary forces as migration and the mating system, rather than to balancing selection and overdominance. Furthermore, we show that biased estimates of expected heterozygosity and among-population differentiation are obtained when using allele frequencies derived from dominant RAPD phenotypes.

What We Don't Know Can Hurt Us: Clinical Inference Bias and Constructed Memories of Sexual Abuse.

The false memory/recovered memory debate, research regarding the malleability of memory, and the current lack of methods for validating recovered memories all support the view that heightened care is required of therapists dealing with clients whom they suspect have been sexually abused. The judgmental heuristics that underlie the major clinical inference biases of confirmatory bias, biased covariation, base rate fallacies, and schematic processing errors are all relevant to the processes leading to therapist-client constructions of memories of sexual abuse. Suggestions for minimizing each of these biases are offered. Personal motivations of the client and client suggestibility are factors that may contribute to the construction of memories of sexual abuse, and suggestions for minimizing the impact of these motivations are offered. In conclusion, general suggestions for minimizing the impact of clinical inference biases within the sexual abuse treatment context are summarized.

Technology diffusion and its effects on social inequalities

We develop a dynamic general-equilibrium framework in which growth is driven by skill-biased technology diffusion. The model incorporates leisure–labor decisions and human capital accumulation through education. We are able to reproduce the trends in income inequality and labor and skills supplies observed in the United States between 1969 and 1996. The paper also provides an explanation for why more individuals invest in human capital when the investment premium is going down, and why the skill-premium goes up when the skills supply is increasing.

Distribution of planktonic foraminifera and paleotemperature reconstruction for the Subantarctic Zone of the South Atlantic

Pleistocene summer sea-surface temperatures (SSST) have been reconstructed on a composite core section recovered in the Subantarctic Zone of the Southern Ocean from planktonic foraminifers applying the Modern Analog Technique. The composite consists of Core PS2489-2 and the sections recovered at ODP Site 1090, and documents the last 1.83 Ma. Three distinct climatic periods can be identified that mirror the Pleistocene development of the Southern Ocean hydrography. Cold climatic conditions prevailed at 43°S during glacial as well as during interglacial periods during the early Pleistocene (1.83-0.87 Ma), indicating a northward shift of isotherms that characterize the present-day Polar Front Zone by about 7° of latitude. Evidence shows a strong linkage between Southern Ocean and low latitude climate during that interval time. Between the Mid-Pleistocene Revolution (ca. 0.9 Ma) and the Mid-Brunhes Event (ca. 0.4 Ma), we observe higher amplitude fluctuations in the SSST between glacial and interglacial periods, corresponding to the temperature range between the present Polar Front and Subantarctic Front. These climatic variations have been related to changes in the northern hemisphere ice sheets. The past 0.4 Ma are characterized by strong SSST variations, of up to 8°C, between glacials and interglacials. Only during the climatic optima (stages 11.3, 9.3, 7.5, 7.1, 5.5, and the early Holocene), SSST exceeded present SSST at the core locality (10.2°C). Although the carbonate dissolution record exhibits high variability during the Pleistocene, it can be shown that SSST estimates were not significantly biased. The Mid-Brunhes dissolution cycle as well as the Mid-Pleistocene enhanced carbonate preservation appear to belong to a global long-term variability in carbonate preservation.

Global 2009 1km MODIS (MOD35/MOD09) cloud frequency and MOD35 processing path

Identifying cloud interference in satellite-derived data is a critical step toward developing useful remotely sensed products. Most MODIS land products use a combination of the MODIS (MOD35) cloud mask and the 'internal' cloud mask of the surface reflectance product (MOD09) to mask clouds, but there has been little discussion of how these masks differ globally. We calculated global mean cloud frequency for both products, for 2009, and found that inflated proportions of observations were flagged as cloudy in the Collection 5 MOD35 product. These erroneously categorized areas were spatially and environmentally non-random and usually occurred over high-albedo land-cover types (such as grassland and savanna) in several regions around the world. Additionally, we found that spatial variability in the processing path applied in the Collection 5 MOD35 algorithm affects the likelihood of a cloudy observation by up to 20% in some areas. These factors result in abrupt transitions in recorded cloud frequency across landcover and processing-path boundaries impeding their use for fine-scale spatially contiguous modeling applications. We show that together, these artifacts have resulted in significantly decreased and spatially biased data availability for Collection 5 MOD35-derived composite MODIS land products such as land surface temperature (MOD11) and net primary productivity (MOD17). Finally, we compare our results to mean cloud frequency in the new Collection 6 MOD35 product, and find that landcover artifacts have been reduced but not eliminated. Collection 6 thus increases data availability for some regions and land cover types in MOD35-derived products but practitioners need to consider how the remaining artifacts might affect their analysis.

Occupational titles and supposed gender-neutrality : A corpus-based diachronic study on gender-neutral occupational titles in American English

Traditionally, some occupational titles have been explicitly marked for the gender of the group dominating the occupation. For example, in male-dominated occupations, titles often end with -man. However, since the second-wave feminist movement, several of the previously gender-biased titles have been supplemented by new, gender-neutral titles. Previous research has shown a discrepancy between researchers regarding the implications of these new titles. Some argue that the gender-neutral titles are only used for female referents, whereas others claim that gender-neutral titles, especially for male- dominated occupations, tend to still presuppose maleness. In the present paper, a corpus-based study is conducted on a few selected occupational titles. The aim is to investigate whether the gender-neutral alternatives have increased in usage over time, and whether the gender-biased ones have decreased. In addition, the study aims at examining whether the gender-neutral forms tend to be used primarily for women or men. The present study is corpus-based, examining the particular terms in the TIME Magazine Corpus. The results of the study show that there has been an increase of the gender-neutral forms since their introduction to English, and that they are primarily used when there is no explicit gender referencing. Proposed explanations for these results are that it may depend on the type of work involved in the selected occupations, as well as them being male-dominated. Furthermore, the results indicate that the gender- neutral terms are opted for when gender is either unknown or irrelevant for the context. 

Borderless Fandom and Contemporary Popular Cultural Scene in Chinese Cyberspace

Thesis (Ph.D.)--University of Washington, 2016-06

Inflation expectations, interest rates and arbitrary income transfers

Unexpected inflation, disinflation or deflation cause arbitrary income transfers between an economy's borrowers and lenders. This redistribution results from distorted real interest rates that are too high when price level changes are over-predicted and too low when they are under-predicted. This article shows that in Australia's case, inflation expectations were mostly biased upwards throughout the 1990s, according to the Melbourne Institute of Applied Economic and Social Research series and to a new derived series based on bond yields, implying that real interest rates were too high over this time. In turn, this caused substantial arbitrary income transfers from debtors to creditors, estimated to have averaged up to 3 per cent of gross domestic product over the period.