Temporal order processing of syllables in the left parietal lobe

Speech processing requires the temporal parsing of syllable order. Individuals suffering from posterior left hemisphere brain injury often exhibit temporal processing deficits as well as language deficits. Although the right posterior inferior parietal lobe has been implicated in temporal order judgments (TOJs) of visual information, there is limited evidence to support the role of the left inferior parietal lobe (IPL) in processing syllable order. The purpose of this study was to examine whether the left inferior parietal lobe is recruited during temporal order judgments of speech stimuli. Functional magnetic resonance imaging data were collected on 14 normal participants while they completed the following forced-choice tasks: (1) syllable order of multisyllabic pseudowords, (2) syllable identification of single syllables, and (3) gender identification of both multisyllabic and monosyllabic speech stimuli. Results revealed increased neural recruitment in the left inferior parietal lobe when participants made judgments about syllable order compared with both syllable identification and gender identification. These findings suggest that the left inferior parietal lobe plays an important role in processing syllable order and support the hypothesized role of this region as an interface between auditory speech and the articulatory code. Furthermore, a breakdown in this interface may explain some components of the speech deficits observed after posterior damage to the left hemisphere

Genomic analysis of Xenopus organizer function

BACKGROUND: Studies of the Xenopus organizer have laid the foundation for our understanding of the conserved signaling pathways that pattern vertebrate embryos during gastrulation. The two primary activities of the organizer, BMP and Wnt inhibition, can regulate a spectrum of genes that pattern essentially all aspects of the embryo during gastrulation. As our knowledge of organizer signaling grows, it is imperative that we begin knitting together our gene-level knowledge into genome-level signaling models. The goal of this paper was to identify complete lists of genes regulated by different aspects of organizer signaling, thereby providing a deeper understanding of the genomic mechanisms that underlie these complex and fundamental signaling events. RESULTS: To this end, we ectopically overexpress Noggin and Dkk-1, inhibitors of the BMP and Wnt pathways, respectively, within ventral tissues. After isolating embryonic ventral halves at early and late gastrulation, we analyze the transcriptional response to these molecules within the generated ectopic organizers using oligonucleotide microarrays. An efficient statistical analysis scheme, combined with a new Gene Ontology biological process annotation of the Xenopus genome, allows reliable and faithful clustering of molecules based upon their roles during gastrulation. From this data, we identify new organizer-related expression patterns for 19 genes. Moreover, our data sub-divides organizer genes into separate head and trunk organizing groups, which each show distinct responses to Noggin and Dkk-1 activity during gastrulation. CONCLUSION: Our data provides a genomic view of the cohorts of genes that respond to Noggin and Dkk-1 activity, allowing us to separate the role of each in organizer function. These patterns demonstrate a model where BMP inhibition plays a largely inductive role during early developmental stages, thereby initiating the suites of genes needed to pattern dorsal tissues. Meanwhile, Wnt inhibition acts later during gastrulation, and is essential for maintenance of organizer gene expression throughout gastrulation, a role which may depend on its ability to block the expression of a host of ventral, posterior, and lateral fate-specifying factors

Climatic Controls on a Holocene Mercury Stable Isotope Sediment Record of Lake Titicaca

Mercury (Hg) records in sediment archives inform past patterns of Hg deposition and the anthropogenic contribution to global Hg cycling. Natural climate variations complicate the interpretation of past Hg accumulation rates (HgARs), warranting additional research. Here, we investigated Hg stable isotopes in a ca. 8k year-long sediment core of Lake Titicaca and combined isotopic data with organic biomarkers and biogeochemical measurements. A wet period in the early Holocene (8000-7300 BP) induced strong watershed erosion, leading to a high HgAR (20.2 ± 6.9 μg m -2 year -1 ), which exceeded the 20th century HgAR (8.4 ± 1.0 μg m -2 year -1 ). Geogenic Hg input dominated during the early Holocene ( f geog = 79%) and played a minor role during the mid- to late Holocene (4500 BP to present; f geog = 20%) when atmospheric Hg deposition dominated. Sediment Δ 200 Hg values and the absence of terrestrial lignin biomarkers suggest that direct lake uptake of atmospheric Hg(0), and subsequent algal scavenging of lake Hg, represented an important atmospheric deposition pathway (42%) during the mid- to late Holocene. During wet episodes of the late Holocene (2400 BP to present), atmospheric Hg(II) deposition was the dominant source of lake sediment Hg (up to 82%). Sediment Δ 199 Hg values suggest that photochemical reduction and re-emission of Hg(0) occurred from the lake surface. Hg stable isotopes show promise as proxies for understanding the history of Hg sources and transformations and help to disentangle anthropogenic and climate factors influencing HgAR observed in sediment archives

GRP94 (gp96) and GRP94 N-Terminal Geldanamycin Binding Domain Elicit Tissue Nonrestricted Tumor Suppression

In chemical carcinogenesis models, GRP94 (gp96) elicits tumor-specific protective immunity. The tumor specificity of this response is thought to reflect immune responses to GRP94-bound peptide antigens, the cohort of which uniquely identifies the GRP94 tissue of origin. In this study, we examined the apparent tissue restriction of GRP94-elicited protective immunity in a 4T1 mammary carcinoma model. We report that the vaccination of BALB/c mice with irradiated fibroblasts expressing a secretory form of GRP94 markedly suppressed 4T1 tumor growth and metastasis. In addition, vaccination with irradiated cells secreting the GRP94 NH2-terminal geldanamycin-binding domain (NTD), a region lacking canonical peptide-binding motifs, yielded a similar suppression of tumor growth and metastatic progression. Conditioned media from cultures of GRP94 or GRP94 NTD-secreting fibroblasts elicited the up-regulation of major histocompatibility complex class II and CD86 in dendritic cell cultures, consistent with a natural adjuvant function for GRP94 and the GRP94 NTD. Based on these findings, we propose that GRP94-elicited tumor suppression can occur independent of the GRP94 tissue of origin and suggest a primary role for GRP4 natural adjuvant function in antitumor immune responses

An Improved Trajectory Model to Evaluate the Collection Performance of Snow Gauges

Recent studies have used numerical models to estimate the collection efficiency\ud of solid precipitation gauges when exposed to the wind, in both\ud shielded and unshielded configurations. The models used computational fluid\ud dynamics (CFD) simulations of the airflow pattern generated by the aerodynamic\ud response to the gauge/shield geometry. These are used as initial conditions\ud to perform Lagrangian tracking of solid precipitation particles. Validation\ud of the results against field observations yielded similarities in the overall\ud behavior, but the model output only approximately reproduced the dependence\ud of the experimental collection efficiency on wind speed. This paper\ud presents an improved snowflake trajectory modeling scheme due to the inclusion\ud of a dynamically-determined drag coefficient. The drag coefficient\ud was estimated using the local Reynolds number as derived from CFD simulations\ud within a time-independent Reynolds Averaged Navier-Stokes (RANS)\ud approach. The proposed dynamic model greatly improves the consistency of\ud results with the field observations recently obtained at the Marshall, CO Winter\ud Precipitation Testbed

IFPA meeting 2016 workshop report I: Genomic communication, bioinformatics, trophoblast biology and transport systems

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2016 there were twelve themed workshops, four of which are summarized in this report. These workshops covered innovative technologies applied to new and traditional areas of placental research: 1) genomic communication; 2) bioinformatics; 3) trophoblast biology and pathology; 4) placental transport systems

Histamine stimulates the proliferation of small and large cholangiocytes by activation of both IP3/Ca2+ and cAMP-dependent signaling mechanisms

Although large cholangiocytes exert their functions by activation of cyclic adenosine 3',5'-monophosphate (cAMP), Ca(2+)-dependent signaling regulates the function of small cholangiocytes. Histamine interacts with four receptors, H1-H4HRs. H1HR acts by Gαq activating IP(3)/Ca(2+), whereas H2HR activates Gα(s) stimulating cAMP. We hypothesize that histamine increases biliary growth by activating H1HR on small and H2HR on large cholangiocytes. The expression of H1-H4HRs was evaluated in liver sections, isolated and cultured (normal rat intrahepatic cholangiocyte culture (NRIC)) cholangiocytes. In vivo, normal rats were treated with histamine or H1-H4HR agonists for 1 week. We evaluated: (1) intrahepatic bile duct mass (IBDM); (2) the effects of histamine, H1HR or H2HR agonists on NRIC proliferation, IP(3) and cAMP levels and PKCα and protein kinase A (PKA) phosphorylation; and (3) PKCα silencing on H1HR-stimulated NRIC proliferation. Small and large cholangiocytes express H1-H4HRs. Histamine and the H1HR agonist increased small IBDM, whereas histamine and the H2HR agonist increased large IBDM. H1HR agonists stimulated IP(3) levels, as well as PKCα phosphorylation and NRIC proliferation, whereas H2HR agonists increased cAMP levels, as well as PKA phosphorylation and NRIC proliferation. The H1HR agonist did not increase proliferation in PKCα siRNA-transfected NRICs. The activation of differential signaling mechanisms targeting small and large cholangiocytes is important for repopulation of the biliary epithelium during pathologies affecting different-sized bile ducts

POLARIS: polygenic LD-adjusted risk score approach for set-based analysis of GWAS data

Polygenic risk scores (PRSs) are a method to summarise the additive trait variance captured by a set of SNPs, and can increase the power of set-based analyses by leveraging public GWAS datasets. PRS aims to assess the genetic liability to some phenotype on the basis of polygenic risk for the same or di�erent phenotype estimated from independent data. We propose the application of PRSs as a set-based method with an additional component of adjustment for linkage disequilibrium (LD), with potential extension of the PRS approach to analyse biologically meaningful SNP sets. We call this method POLARIS: POlygenic Ld-Adjusted RIsk Score. POLARIS identi�es the LD-structure of SNPs using spectral decomposition of the SNP correlation matrix and replaces the individuals' SNP allele counts with LD-adjusted dosages. Using a raw genotype dataset together with SNP e�ect sizes from a second independent dataset, POLARIS can be used for set-based analysis. MAGMA is an alternative set-based approach employing principal component analysis to account for LD between markers in a raw genotype dataset. We used simulations, both with simple constructed and real LD-structure, to compare the power of these methods. POLARIS shows more power than MAGMA applied to the raw genotype dataset only, but less or comparable power to combined analysis of both datasets. POLARIS has the advantages that it produces a risk score per person per set using all available SNPs, and aims to increase power by leveraging the e�ect sizes from the discovery set in a self-contained test of association in the test dataset

State of the field: digital history

Computing and the use of digital sources and resources is an everyday and essential practice in current academic scholarship. The present article gives a concise overview of approaches and methods within digital historical scholarship, focussing on the question: How have the Digital Humanities evolved and what has that evolution brought to historical scholarship? We begin by discussing techniques in which data are generated and machine searchable, such as OCR/HTR, born-digital archives, computer vision, scholarly editions, and Linked Data. In the second section, we provide examples of how data is made more accessible through quantitative text and network analysis. We close with a section on the need for hermeneutics and data-awareness in digital historical scholarship. The technologies described in this article have had varying degrees of effect on historical scholarship, usually in indirect ways. For example, technologies such as OCR and search engines may not be directly visible in a historical argument; however, these technologies do shape how historians interact with sources and whether sources can be accessed at all. It is with this article that we aim to start to take stock of the digital approaches and methods used in historical scholarship which may serve as starting points for scholars to understand the digital turn in the field and how and when to implement such approaches in their work