Histology of “placoderm” dermal skeletons: Implications for the nature of the ancestral gnathostome

The vertebrate dermal skeleton has long been interpreted to have evolved from a primitive condition exemplified by chondrichthyans. However, chondrichthyans and osteichthyans evolved from an ancestral gnathostome stem‐lineage in which the dermal skeleton was more extensively developed. To elucidate the histology and skeletal structure of the gnathostome crown‐ancestor we conducted a histological survey of the diversity of the dermal skeleton among the placoderms, a diverse clade or grade of early jawed vertebrates. The dermal skeleton of all placoderms is composed largely of a cancellar architecture of cellular dermal bone, surmounted by dermal tubercles in the most ancestral clades, including antiarchs. Acanthothoracids retain an ancestral condition for the dermal skeleton, and we record its secondary reduction in antiarchs. We also find that mechanisms for remodeling bone and facilitating different growth rates between adjoining plates are widespread throughout the placoderms. J. Morphol., 2013. © 2013 Wiley Periodicals, Inc.     

Germline HOXB13 p.Gly84Glu mutation and risk of colorectal cancer

Introduction: The HOXB13 pGly84Glu mutation has recently been associated with an increased risk of prostate cancer but the association of other cancer sites with this allele has not been assessed. Data has suggested that HOXB13 expression levels are decreased in colorectal cancer (CRC) cell lines indicating this gene may be involved in colorectal tumourigenesis. Methods: To evaluate a potential association of this mutation with CRC, we genotyped the mutation in 2695 CRC cases and 4593 controls from population-based registries in Canada and Australia. Results: The HOXB13 pGly84Glu mutation was more common in CRC cases than controls (0.48% vs. 0.17%, P = 0.02) indicating a significant association between the HOXB13 variant and CRC risk (OR = 2.8; 95%CI: 1.2–6.8). This association was attenuated but remained significant with the inclusion of previously published and publicly available genotype data. Pedigree analysis of cases and controls revealed that 7/21 HOXB13 mutation carriers had a family history of prostate cancer. Discussion: This report is the first to suggest a risk of CRC associated with mutations in the HOXB13 gene. These findings require further validation but may be of importance in the screening and genetic counseling of families known to carry the HOXB13 pGly84Glu mutation.     

Survival of Phytophthora cinnamomi as oospores,stromata, and thick-walled chlamydospores in roots of symptomatic and asymptomatic annual and herbaceous perennial plant species

Studies were conducted to determine how Phytophthora cinnamomi survives during hot and dry Mediterranean summers in areas with limited surviving susceptible hosts.     

Characterization of Phytophthora hybrids from ITS clade 6 associated with riparian ecosystems in South Africa and Australia

Surveys of Australian and South African rivers revealed numerous Phytophthora isolates residing in clade 6 of the genus, with internal transcribed spacer (ITS) gene regions that were either highly polymorphic or unsequenceable. These isolates were suspected to be hybrids. Three nuclear loci, the ITS region, two single copy loci (antisilencing factor (ASF) and G protein alpha subunit (GPA)), and one mitochondrial locus (cytochrome oxidase c subunit I (coxI)) were amplified and sequenced to test this hypothesis. Abundant recombination within the ITS region was observed. This, combined with phylogenetic comparisons of the other three loci, confirmed the presence of four different hybrid types involving the three described parent species Phytophthora amnicola, Phytophthora thermophila, and Phytophthora taxon PgChlamydo. In all cases, only a single coxI allele was detected, suggesting that hybrids arose from sexual recombination. All the hybrid isolates were sterile in culture and all their physiological traits tended to resemble those of the maternal parents. Nothing is known regarding their host range or pathogenicity. Nonetheless, as several isolates from Western Australia were obtained from the rhizosphere soil of dying plants, they should be regarded as potential threats to plant health. The frequent occurrence of the hybrids and their parent species in Australia strongly suggests an Australian origin and a subsequent introduction into South Africa.     

Regulation of Inflammation by IL-17A and IL-17F Modulates Non-Alcoholic Fatty Liver Disease Pathogenesis

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. While it is well-accepted that inflammation is central to NAFLD pathogenesis, the immune pathway(s) orchestrating disease progression are poorly defined. Notably, IL-17RA signaling, via IL-17A, plays an important role in obesity-driven NAFLD pathogenesis. However, the role of the IL-17F, another IL-17RA ligand, in NAFLD pathogenesis has not been examined. Further, the cell types expressing IL-17RA and producing IL-17RA ligands in the pathogenesis of NAFLD have not been defined. Here, IL-17RA^-/-, IL-17A^-/-, IL-17F^-/- and wild-type (WT) mice were fed either standard chow diet or methionine and choline deficient diet (MCDD)—a diet known to induce steatosis and hepatic inflammation through beta-oxidation dysfunction—and hepatic inflammation and NAFLD progression were subsequently quantified. MCDD feeding augmented hepatic IL-17RA expression and significantly increased hepatic infiltration of macrophages and IL-17A and IL-17F producing CD4⁺ and CD8⁺ T cells in WT mice. In contrast, IL-17RA^-/-, IL-17A^-/-, and IL-17F^-/- mice, despite increased steatosis, exhibited significant protection from hepatocellular damage compared to WT controls. Protection from hepatocellular damage correlated with decreased levels of hepatic T-cell and macrophage infiltration and decreased expression of inflammatory mediators associated with NAFLD. In sum, our results indicate that the IL-17 axis also plays a role in a MCDD-induced model of NAFLD pathogenesis. Further, we show for the first time that IL-17F, and not only IL-17A, plays an important role in NAFLD driven inflammation.     

Expression of mRNA Encoding Mcu and Other Mitochondrial Calcium Regulatory Genes Depends on Cell Type,Neuronal Subtype,and Ca2+ Signaling

Uptake of Ca²⁺ into the mitochondrial matrix controls cellular metabolism and survival-death pathways. Several genes are implicated in controlling mitochondrial Ca²⁺ uptake (mitochondrial calcium regulatory genes, MCRGs), however, less is known about the factors which influence their expression level. Here we have compared MCRG mRNA expression, in neural cells of differing type (cortical neurons vs. astrocytes), differing neuronal subtype (CA3 vs. CA1 hippocampus) and in response to Ca²⁺ influx, using a combination of qPCR and RNA-seq analysis. Of note, we find that the Mcu-regulating Micu gene family profile differs substantially between neurons and astrocytes, while expression of Mcu itself is markedly different between CA3 and CA1 regions in the adult hippocampus. Moreover, dynamic control of MCRG mRNA expression in response to membrane depolarization-induced Ca²⁺ influx is also apparent, resulting in repression of Letm1, as well as Mcu. Thus, the mRNA expression profile of MCRGs is not fixed, which may cause differences in the coupling between cytoplasmic and mitochondrial Ca²⁺, as well as diversity of mitochondrial Ca²⁺ uptake mechanisms.     

The Association between EGFR and cMET Expression and Phosphorylation and Its Prognostic Implication in Patients with Breast Cancer

EGFR and cMET cross-talk is involved in breast cancer (BC) progression and resistance to different targeted therapies, however little is known about the co-expression patterns of EGFR and cMET or its prognostic significance in BC. Protein levels of EGFR, cMET and their phosphorylated proteins were measured in 825 BC samples using reverse phase protein array (RPPA). Given unimodal distribution of proteins, the median was selected as a cut-off after sensitivity analyses. Kaplan-Meier survival curves were used to estimate relapse-free (RFS) and overall survival (OS). Cox-proportional hazards models were utilized to determine associations between EGFR and cMET with outcomes. Mean age was 58 years with 457 (55%) hormone receptor (HR) positive, 211 (26%) triple-negative (TN) and 148 (18%) HER2 positive tumors (HER2+). HER2+ was associated with higher EGFR expression and phosphorylation, compared to HR and TN (p<0.05). High EGFR expression was associated with higher phosphorylated-cMET (p-cMET) but not cMET (ANOVA p-cMET p < 0.001; cMET p = 0.34). The same association was found with high phosphorylated-EGFR (p-EGFR) group at Tyr992 and Tyr1068 (both p < 0.001). High expressions in either of two p-EGFRs were linked with higher cMET as well (all p<0.001). For the TN subtype, high expression in EGFR and p-EGFR at Tyr992 but not at Tyr1068 was associated with higher p-cMET (p<0.00, p = 0.012, p = 0.4 respectively). Only high expression in p-EGFR at Tyr992 was linked with higher expression of cMET (p = 0.02). In contrast, among HER2 subtype, high expression in p-EGFR at Tyr1068 but not at Tyr992 was associated with higher cMET and p-cMET (cMET p = 0.023;p-cMET p<0.001). Four subgroups of patients defined by dichotomized EGFR/p-EGFR and cMET/p-cMET level demonstrated no significant differences in survival. In multivariate analyses, neither cMET nor EGFR expression/activation was found to be an independent prognostic factor in survival outcome.     

Redrawing the US Obesity Landscape: Bias-Corrected Estimates of State-Specific Adult Obesity Prevalence

Background

State-level estimates from the Centers for Disease Control and Prevention (CDC) underestimate the obesity epidemic because they use self-reported height and weight. We describe a novel bias-correction method and produce corrected state-level estimates of obesity and severe obesity.

Methods

Using non-parametric statistical matching, we adjusted self-reported data from the Behavioral Risk Factor Surveillance System (BRFSS) 2013 (n = 386,795) using measured data from the National Health and Nutrition Examination Survey (NHANES) (n = 16,924). We validated our national estimates against NHANES and estimated bias-corrected state-specific prevalence of obesity (BMI≥30) and severe obesity (BMI≥35). We compared these results with previous adjustment methods.

Results

Compared to NHANES, self-reported BRFSS data underestimated national prevalence of obesity by 16% (28.67% vs 34.01%), and severe obesity by 23% (11.03% vs 14.26%). Our method was not significantly different from NHANES for obesity or severe obesity, while previous methods underestimated both. Only four states had a corrected obesity prevalence below 30%, with four exceeding 40%–in contrast, most states were below 30% in CDC maps.

Conclusions

Twelve million adults with obesity (including 6.7 million with severe obesity) were misclassified by CDC state-level estimates. Previous bias-correction methods also resulted in underestimates. Accurate state-level estimates are necessary to plan for resources to address the obesity epidemic.     

Models of Eucalypt phenology predict bat population flux

Fruit bats (Pteropodidae) have received increased attention after the recent emergence of notable viral pathogens of bat origin. Their vagility hinders data collection on abundance and distribution, which constrains modeling efforts and our understanding of bat ecology, viral dynamics, and spillover. We addressed this knowledge gap with models and data on the occurrence and abundance of nectarivorous fruit bat populations at 3 day roosts in southeast Queensland. We used environmental drivers of nectar production as predictors and explored relationships between bat abundance and virus spillover. Specifically, we developed several novel modeling tools motivated by complexities of fruit bat foraging ecology, including: (1) a dataset of spatial variables comprising Eucalypt‐focused vegetation indices, cumulative precipitation, and temperature anomaly; (2) an algorithm that associated bat population response with spatial covariates in a spatially and temporally relevant way given our current understanding of bat foraging behavior; and (3) a thorough statistical learning approach to finding optimal covariate combinations. We identified covariates that classify fruit bat occupancy at each of our three study roosts with 86–93% accuracy. Negative binomial models explained 43–53% of the variation in observed abundance across roosts. Our models suggest that spatiotemporal heterogeneity in Eucalypt‐based food resources could drive at least 50% of bat population behavior at the landscape scale. We found that 13 spillover events were observed within the foraging range of our study roosts, and they occurred during times when models predicted low population abundance. Our results suggest that, in southeast Queensland, spillover may not be driven by large aggregations of fruit bats attracted by nectar‐based resources, but rather by behavior of smaller resident subpopulations. Our models and data integrated remote sensing and statistical learning to make inferences on bat ecology and disease dynamics. This work provides a foundation for further studies on landscape‐scale population movement and spatiotemporal disease dynamics.     

Macrophytes moderate the taxonomic and functional composition of phytoplankton assemblages during a nutrient loading experiment

相似文献