Pink verrucous plaque in a man with systemic mastocytosis

Porokeratosis ptychotropica is a rare and commonly misdiagnosed subtype of porokeratosis involving the body folds. We present a 53-year-old man with systemic mastocytosis who presented with a pruritic, verrucous plaque in the gluteal fold that showed multiple cornoid lamellae on histopathologic evaluation, diagnostic of porokeratosis ptychotropica. Various treatments have been reported, including topical corticosteroids, retinoids, vitamin D analogs, calcineurin inhibitors, imiquimod, phototherapy, cryotherapy, or ablative laser therapy, but recurrences are common

The pseudomonas aeruginosa secreted protein PA2934 decreases apical membrane expression of the cystic fibrosis transmembrane conductance regulator

We previously reported that Pseudomonas aeruginosa PA14 secretes a protein that can reduce the apical membrane expression of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Here we report that we have used a proteomic approach to identify this secreted protein as PA2394, and we have named the gene cif, for CFTR inhibitory factor. We demonstrate that Cif is a secreted protein and is found associated with outer membrane-derived vesicles. Expression of Cif in Escherichia coli and purification of the C-terminal six-His-tagged Cif protein showed that Cif is necessary and sufficient to mediate the reduction in apical membrane expression of CFTR and a concomitant reduction in CFTR-mediated Cl&minus; ion secretion. Cif demonstrates epoxide hydrolase activity in vitro and requires a highly conserved histidine residue identified in &alpha;/&beta; hydrolase family enzymes to catalyze this reaction. Mutating this histidine residue also abolishes the ability of Cif to reduce apical membrane CFTR expression. Finally, we demonstrate that the cif gene is expressed in the cystic fibrosis (CF) lung and that nonmucoid isolates of P. aeruginosa show greater expression of the gene than do mucoid isolates. We propose a model in which the Cif-mediated decrease in apical membrane expression of CFTR by environmental isolates of P. aeruginosa facilitates the colonization of the CF lung by this microbe. <br /

The potential for CO \u3c inf\u3e 2 -induced acidification in freshwater: A great lakes case study

Ocean acidification will likely result in a drop of 0.3–0.4 pH units in the surface ocean by 2100, assuming anthropogenic CO2 emissions continue at the current rate. Impacts of increasing atmospheric pCO2 on pH in freshwater systems have scarcely been addressed. In this study, the Laurentian Great Lakes are used as a case study for the potential for CO2-induced acidification in freshwater systems as well as for assessment of the ability of current water quality monitoring to detect pH trends. If increasing atmospheric pCO2 is the only forcing, pH will decline in the Laurentian Great Lakes at the same rate and magnitude as the surface ocean through 2100. High-resolution numerical models and one high-resolution time series of data illustrate that the pH of the Great Lakes has significant spatio-temporal variability. Because of this variability, data from existing monitoring systems are insufficient to accurately resolve annual mean trends. Significant measurement uncertainty also impedes the ability to assess trends. To elucidate the effects of increasing atmospheric CO2 in the Great Lakes requires pH monitoring by collecting more accurate measurements with greater spatial and temporal coverage

Are the metabolomic responses to folivory of closely related plant species linked to macroevolutionary and plant-folivore coevolutionary processes?

Altres ajuts: MAGRAMA/OAPN-022/2008The debate whether the coevolution of plants and insects or macroevolutionary processes (phylogeny) is the main driver determining the arsenal of molecular defensive compounds of plants remains unresolved. Attacks by herbivorous insects affect not only the composition of defensive compounds in plants but also the entire metabolome. Metabolomes are the final products of genotypes and are constrained by macroevolutionary processes, so closely related species should have similar metabolomic compositions and may respond in similar ways to attacks by folivores. We analyzed the elemental compositions and metabolomes of needles from three closely related Pinus species with distant coevolutionary histories with the caterpillar of the processionary moth respond similarly to its attack. All pines had different metabolomes and metabolic responses to herbivorous attack. The metabolomic variation among the species and the responses to folivory reflected their macroevolutionary relationships, with P. pinaster having the most divergent metabolome. The concentrations of terpenes were in the attacked trees supporting the hypothesis that herbivores avoid plant individuals with higher concentrations. Our results suggest that macroevolutionary history plays important roles in the metabolomic responses of these pine species to folivory, but plant-insect coevolution probably constrains those responses. Combinations of different evolutionary factors and trade-offs are likely responsible for the different responses of each species to folivory, which is not necessarily exclusively linked to plant-insect coevolution

Deconstruction of Holistic Rubrics into Analytic Rubrics for Large-Scale Assessments of Students’ Reasoning of Complex Science Concepts

Constructed responses can be used to assess the complexity of student thinking and can be evaluated using rubrics. The two most typical rubric types used are holistic and analytic. Holistic rubrics may be difficult to use with expert-level reasoning that has additive or overlapping language. In an attempt to unpack complexity in holistic rubrics at a large scale, we have developed a systematic approach called deconstruction. We define deconstruction as the process of converting a holistic rubric into defining individual conceptual components that can be used for analytic rubric development and application. These individual components can then be recombined into the holistic score which keeps true to the holistic rubric purpose, while maximizing the benefits and minimizing the shortcomings of each rubric type. This paper outlines the deconstruction process and presents a case study that shows defined concept definitions for a hierarchical holistic rubric developed for an undergraduate physiology-content reasoning context. These methods can be used as one way for assessment developers to unpack complex student reasoning, which may ultimately improve reliability and validation of assessments that are targeted at uncovering large-scale complex scientific reasoning. Accessed 398 times on https://pareonline.net from September 05, 2019 to December 31, 2019. For downloads from January 1, 2020 forward, please click on the PlumX Metrics link to the right

Histone locus regulation by the Drosophila dosage compensation adaptor protein CLAMP

The conserved histone locus body (HLB) assembles prior to zygotic gene activation early during development and concentrates factors into a nuclear domain of coordinated histone gene regulation. Although HLBs form specifically at replication-dependent histone loci, the cis and trans factors that target HLB components to histone genes remained unknown. Here we report that conserved GA repeat cis elements within the bidirectional histone3–histone4 promoter direct HLB formation in Drosophila. In addition, the CLAMP (chromatin-linked adaptor for male-specific lethal [MSL] proteins) zinc finger protein binds these GA repeat motifs, increases chromatin accessibility, enhances histone gene transcription, and promotes HLB formation. We demonstrated previously that CLAMP also promotes the formation of another domain of coordinated gene regulation: the dosage-compensated male X chromosome. Therefore, CLAMP binding to GA repeat motifs promotes the formation of two distinct domains of coordinated gene activation located at different places in the genome

Serum and glucocorticoid-inducible kinase1 increases plasma membrane wt-CFTR in human airway epithelial cells by inhibiting its endocytic retrieval

Background: Chloride (Cl) secretion by the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) located in the apical membrane of respiratory epithelial cells plays a critical role in maintenance of the airway surface liquid and mucociliary clearance of pathogens. Previously, we and others have shown that the serum and glucocorticoid-inducible kinase-1 (SGK1) increases wild type CFTR (wt-CFTR) mediated Cl transport in Xenopus oocytes by increasing the amount of wt-CFTR protein in the plasma membrane. However, the effect of SGK1 on the membrane abundance of wt-CFTR in airway epithelial cells has not been examined, and the mechanism whereby SGK1 increases membrane wt-CFTR has also not been examined. Thus, the goal of this study was to elucidate the mechanism whereby SGK1 regulates the membrane abundance of wt-CFTR in human airway epithelial cells. Methods and Results: We report that elevated levels of SGK1, induced by dexamethasone, increase plasma membrane abundance of wt-CFTR. Reduction of SGK1 expression by siRNA (siSGK1) and inhibition of SGK1 activity by the SGK inhibitor GSK 650394 abrogated the ability of dexamethasone to increase plasma membrane wt-CFTR. Overexpression of a constitutively active SGK1 (SGK1-S422D) increased plasma membrane abundance of wt-CFTR. To understand the mechanism whereby SGK1 increased plasma membrane wt-CFTR, we examined the effects of siSGK1 and SGK1-S442D on the endocytic retrieval of wt-CFTR. While siSGK1 increased wt-CFTR endocytosis, SGK1-S442D inhibited CFTR endocytosis. Neither siSGK1 nor SGK1-S442D altered the recycling of endocytosed wt-CFTR back to the plasma membrane. By contrast, SGK1 increased the endocytosis of the epidermal growth factor receptor (EGFR). Conclusion: This study demonstrates for the first time that SGK1 selectively increases wt-CFTR in the plasma membrane of human airway epithelia cells by inhibiting its endocytic retrieval from the membrane. © 2014 Bomberger et al

On the Correlations between Flavour Observables in Minimal U(2)^3 Models

The stringent correlations between flavour observables in models with CMFV are consistent with the present data except for the correlation Delta M_{s,d}-epsilon_K. Motivated by the recent work of Barbieri et al, we compare the CMFV correlations with the ones present in a special class of models with an approximate global U(2)^3 flavour symmetry, constrained by a minimal set of spurions governing the breakdown of this symmetry and the assumption that only SM operators are relevant in flavour physics. This analog of CMFV to be called MU(2)^3 allows to avoid the Delta M_{s,d}-epsilon_K tension in question because of reduced flavour symmetry and implied non-MFV contributions to Delta M_{s,d}. While the patterns of flavour violation in K meson system is the same as in CMFV models, the CP-violation in B_{s,d} meson systems can deviate from the one in the SM and CMFV models. We point out a stringent triple S_{psi K_S}-S_{psi phi}-|V_ub| correlation in this class of models that could in the future provide a transparent distinction between different MU(2)^3 models and in the context of these models determine |V_ub| by means of precise measurements of S_{psi K_S} and S_{psi phi} with only small hadronic uncertainties. For fixed S_{psi K_S} the correlation between B(B^+ -> tau^+nu_tau) and S_{psi phi} follows. We also find that MU(2)^3 models could in principle accommodate a negative value of S_{psi phi}, provided |V_ub| is found to be in the ballpark of exclusive determinations and the particular MU(2)^3 model provides a 25% enhancement of epsilon_K. A supersymmetric U(2)^3 model worked out in the Barbieri-School appears to satisfy these requirements. However if B(B^+ -> tau^+nu_tau)>1.0 10^{-4} will be confirmed by future experiments only positive S_{psi phi} is allowed in this framework. We summarize briefly the pattern of flavour violation in rare K and B_{s,d} decays in MU(2)^3 models.Comment: 28 pages, 6 figures; v2: Few references and discussion on CP violation in B_s-> mu^+ mu^- added; v3: Several clarifying comments added, conclusions unchanged, version accepted for publication in JHE

Sequence Analysis of the IL28A/IL28B Inverted Gene Duplication That Contains Polymorphisms Associated with Treatment Response in Hepatitis C Patients

Several SNPs located in or around the IL28B gene are associated with response of patients infected with Hepatitis C virus to treatment with pegylated interferon-α +/− ribavirin or with spontaneous clearance of the virus. The results of such studies are so compelling that future treatment approaches are likely to involve clinical decisions being made on the basis of a patient's genotype. Since IL28B is a paralogue of IL28A with greater than 95% sequence identity, it is possible that without genotyping assay specificity, sequences in IL28A may contribute to genotype identification, and potentially confound treatment decisions. This study aimed to 1) examine DNA sequences in IL28B surrounding each of the reported associated SNPs and the corresponding regions in IL28A; and 2) develop a robust assay for rs12979860, the most ‘cosmopolitan’ SNP most strongly associated with treatment response across all global populations studied to date. Bioinformatic analysis of genomic regions surrounding IL28A and IL28B demonstrated that 3 SNPs were unique to IL28B, whereas the remaining 6 SNP regions shared >93% identity between IL28A and IL28B. Using a panel of DNA samples, PCR amplification followed by Sanger sequencing was used to examine IL28B SNPs and the corresponding regions in IL28A. For the overlapping SNPs, all 6 in IL28B were confirmed to be polymorphic whereas the corresponding positions in IL28A were monomorphic. Based upon IL28A and IL28B sequence data, a specific TaqMan® assay was developed for SNP rs12979860 that was 100% concordant to the sequence-derived genotypes. Analysis using a commercial assay identified one discordant result which led to a change in their genotype-calling algorithm. Where future treatment decisions are made upon the results of genotyping assays, it is very important that results are concordant with data from a sequence-based format. This is especially so in situations where designing specific PCR primers is a challenge