Fermi surfaces and quasi-particle band dispersions of the iron pnictides superconductor KFe2As2 observed by angle-resolved photoemission spectroscopy

We have performed an angle-resolved photoemission study of the iron pnictide superconductor KFe2As2 with Tc 4 K. Most of the observed Fermi surfaces show almost two-dimensional shapes, while one of the quasi-particle bands near the Fermi level has a strong dispersion along the kz direction, consistent with the result of a band-structure calculation. However, hole Fermi surfaces \alpha and \zeta are smaller than those predicted by the calculation while other Fermi surfaces are larger. These observations are consistent with the result of a de Haas-van Alphen study and a theoretical prediction on inter-band scattering, possibly indicating many body effects on the electronic structure.Comment: 4 pages, 5 figures. Proceeding of the 9th International Conference on Spectroscopies in Novel Superconductors (SNS2010

Data incongruence and the problem of avian louse phylogeny

Recent studies based on different types of data (i.e. morphological and molecular) have supported conflicting phylogenies for the genera of avian feather lice (Ischnocera: Phthiraptera). We analyse new and published data from morphology and from mitochondrial (12S rRNA and COI) and nuclear (EF1-) genes to explore the sources of this incongruence and explain these conflicts. Character convergence, multiple substitutions at high divergences, and ancient radiation over a short period of time have contributed to the problem of resolving louse phylogeny with the data currently available. We show that apparent incongruence between the molecular datasets is largely attributable to rate variation and nonstationarity of base composition. In contrast, highly significant character incongruence leads to topological incongruence between the molecular and morphological data. We consider ways in which biases in the sequence data could be misleading, using several maximum likelihood models and LogDet corrections. The hierarchical structure of the data is explored using likelihood mapping and SplitsTree methods. Ultimately, we concede there is strong discordance between the molecular and morphological data and apply the conditional combination approach in this case. We conclude that higher level phylogenetic relationships within avian Ischnocera remain extremely problematic. However, consensus between datasets is beginning to converge on a stable phylogeny for avian lice, at and below the familial rank

Glucocorticoids with different chemical structures but similar glucocorticoid receptor potency regulate subsets of common and unique genes in human trabecular meshwork cells

<p>Abstract</p> <p>Background</p> <p>In addition to their well-documented ocular therapeutic effects, glucocorticoids (GCs) can cause sight-threatening side-effects including ocular hypertension presumably via morphological and biochemical changes in trabecular meshwork (TM) cells. In the present study, we directly compared the glucocorticoid receptor (GR) potency for dexamethasone (DEX), fluocinolone acetonide (FA) and triamcinolone acetonide (TA), examined the expression of known GRα and GRβ isoforms, and used gene expression microarrays to compare the effects of DEX, FA, and TA on the complete transcriptome in two primary human TM cell lines.</p> <p>Methods</p> <p>GR binding affinity for DEX, FA, and TA was measured by a cell-free competitive radio-labeled GR binding assay. GR-mediated transcriptional activity was assessed using the GeneBLAzer beta-lactamase reporter gene assay. Levels of GRα and GRβ isoforms were assessed by Western blot. Total RNA was extracted from TM 86 and TM 93 cells treated with 1 μM DEX, FA, or TA for 24 hr and used for microarray gene expression analysis. The microarray experiments were repeated three times. Differentially expressed genes were identified by Rosetta Resolver Gene Expression Analysis System.</p> <p>Results</p> <p>The GR binding affinity (IC₅₀) for DEX, FA, and TA was 5.4, 2.0, and 1.5 nM, respectively. These values are similar to the GR transactivation EC₅₀of 3.0, 0.7, and 1.5 nM for DEX, FA, and TA, respectively. All four GRα translational isoforms (A-D) were expressed in TM 86 and TM 93 total cell lysates, however, the C and D isoforms were more highly expressed relative to A and B. All four GRβ isoforms (A-D) were also detected in TM cells, although GRβ-D isoform expression was lower compared to that of the A, B, or C isoforms. Microarray analysis revealed 1,968 and 1,150 genes commonly regulated by DEX, FA, and TA in TM 86 and TM 93, respectively. These genes included RGC32, OCA2, ANGPTL7, MYOC, FKBP5, SAA1 and ZBTB16. In addition, each GC specifically regulated a unique set of genes in both TM cell lines. Using Ingenuity Pathway Analysis (IPA) software, analysis of the data from TM 86 cells showed that DEX significantly regulated transcripts associated with RNA post-transcriptional modifications, whereas FA and TA modulated genes involved in lipid metabolism and cell morphology, respectively. In TM 93 cells, DEX significantly regulated genes implicated in histone methylation, whereas FA and TA altered genes associated with cell cycle and cell adhesion, respectively.</p> <p>Conclusion</p> <p>Human trabecular meshwork cells in culture express all known GRα and GRβ translational isoforms, and GCs with similar potency but subtly different chemical structure are capable of regulating common and unique gene subsets and presumably biologic responses in these cells. These GC structure-dependent effects appear to be TM cell-lineage dependent.</p

The potential risks and impact of the start of the 2015–2016 influenza season in the WHO European Region: a rapid risk assessment

Background: Countries in the World Health Organization (WHO) European Region are reporting more severe influenza activity in the 2015–2016 season compared to previous seasons. Objectives: To conduct a rapid risk assessment to provide interim information on the severity of the current influenza season. Methods: Using the WHO manual for rapid risk assessment of acute public health events and surveillance data available from Flu News Europe, an assessment of the current influenza season from 28 September 2015 (week 40/2015) up to 31 January 2016 (week 04/2016) was made compared with the four previous seasons. Results: The current influenza season started around week 51/2015 with higher influenza activity reported in Eastern Europe compared to Western Europe. There is a strong predominance of influenza A(H1N1)pdm09 compared to previous seasons, but the virus is antigenically similar to the strain included in the seasonal influenza vaccine. Compared to the 2014/2015 season, there was a rapid increase in the number of severe cases in Eastern European countries with the majority of such cases occurring among adults aged < 65 years. Conclusions: The current influenza season is characterized by an early start in Eastern European countries, with indications of a more severe season. Currently circulating influenza A(H1N1)pdm09 viruses are antigenically similar to those included in the seasonal influenza vaccine, and the vaccine is expected to be effective. Authorities should provide information to the public and health providers about the current influenza season, recommendations for the treatment of severe disease and effective public health measures to prevent influenza transmission

Cystatin A, a Potential Common Link for Mutant Myocilin Causative Glaucoma

Myocilin (MYOC) is a 504 aa secreted glycoprotein induced by stress factors in the trabecular meshwork tissue of the eye, where it was discovered. Mutations in MYOC are linked to glaucoma. The glaucoma phenotype of each of the different MYOC mutation varies, but all of them cause elevated intraocular pressure (IOP). In cells, forty percent of wild-type MYOC is cleaved by calpain II, a cysteine protease. This proteolytic process is inhibited by MYOC mutants. In this study, we investigated the molecular mechanisms by which MYOC mutants cause glaucoma. We constructed adenoviral vectors with variants Q368X, R342K, D380N, K423E, and overexpressed them in human trabecular meshwork cells. We analyzed expression profiles with Affymetrix U133Plus2 GeneChips using wild-type and null viruses as controls. Analysis of trabecular meshwork relevant mechanisms showed that the unfolded protein response (UPR) was the most affected. Search for individual candidate genes revealed that genes that have been historically connected to trabecular meshwork physiology and pathology were altered by the MYOC mutants. Some of those had known MYOC associations (MMP1, PDIA4, CALR, SFPR1) while others did not (EDN1, MGP, IGF1, TAC1). Some, were top-changed in only one mutant (LOXL1, CYP1B1, FBN1), others followed a mutant group pattern. Some of the genes were new (RAB39B, STC1, CXCL12, CSTA). In particular, one selected gene, the cysteine protease inhibitor cystatin A (CSTA), was commonly induced by all mutants and not by the wild-type. Subsequent functional analysis of the selected gene showed that CSTA was able to reduce wild-type MYOC cleavage in primary trabecular meshwork cells while an inactive mutated CSTA was not. These findings provide a new molecular understanding of the mechanisms of MYOC-causative glaucoma and reveal CSTA, a serum biomarker for cancer, as a potential biomarker and drug for the treatment of MYOC-induced glaucoma

Uncovering the complex genetics of human temperament

Experimental studies of learning suggest that human temperament may depend on the molecular mechanisms for associative conditioning, which are highly conserved in animals. The main genetic pathways for associative conditioning are known in experimental animals, but have not been identified in prior genome-wide association studies (GWAS) of human temperament. We used a data-driven machine learning method for GWAS to uncover the complex genotypic-phenotypic networks and environmental interactions related to human temperament. In a discovery sample of 2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (i.e., SNP sets) regardless of phenotype. Second, we identified 3 clusters of people with distinct temperament profiles measured by the Temperament and Character Inventory regardless of genotype. Third, we found 51 SNP sets that identified 736 gene loci and were significantly associated with temperament. The identified genes were enriched in pathways activated by associative conditioning in animals, including the ERK, PI3K, and PKC pathways. 74% of the identified genes were unique to a specific temperament profile. Environmental influences measured in childhood and adulthood had small but significant effects. We confirmed the replicability of the 51 Finnish SNP sets in healthy Korean (90%) and German samples (89%), as well as their associations with temperament. The identified SNPs explained nearly all the heritability expected in each sample (37-53%) despite variable cultures and environments. We conclude that human temperament is strongly influenced by more than 700 genes that modulate associative conditioning by molecular processes for synaptic plasticity and long-term memory.Peer reviewe

Network analysis of human glaucomatous optic nerve head astrocytes

<p>Abstract</p> <p>Background</p> <p>Astrocyte activation is a characteristic response to injury in the central nervous system, and can be either neurotoxic or neuroprotective, while the regulation of both roles remains elusive.</p> <p>Methods</p> <p>To decipher the regulatory elements controlling astrocyte-mediated neurotoxicity in glaucoma, we conducted a systems-level functional analysis of gene expression, proteomic and genetic data associated with reactive optic nerve head astrocytes (ONHAs).</p> <p>Results</p> <p>Our reconstruction of the molecular interactions affected by glaucoma revealed multi-domain biological networks controlling activation of ONHAs at the level of intercellular stimuli, intracellular signaling and core effectors. The analysis revealed that synergistic action of the transcription factors AP-1, vitamin D receptor and Nuclear Factor-kappaB in cross-activation of multiple pathways, including inflammatory cytokines, complement, clusterin, ephrins, and multiple metabolic pathways. We found that the products of over two thirds of genes linked to glaucoma by genetic analysis can be functionally interconnected into one epistatic network via experimentally-validated interactions. Finally, we built and analyzed an integrative disease pathology network from a combined set of genes revealed in genetic studies, genes differentially expressed in glaucoma and closely connected genes/proteins in the interactome.</p> <p>Conclusion</p> <p>Our results suggest several key biological network modules that are involved in regulating neurotoxicity of reactive astrocytes in glaucoma, and comprise potential targets for cell-based therapy.</p

Feshbach resonances and mesoscopic phase separation near a quantum critical point in multiband FeAs-based superconductors

High Tc superconductivity in FeAs-based multilayers (pnictides), evading temperature decoherence effects in a quantum condensate, is assigned to a Feshbach resonance (called also shape resonance) in the exchange-like interband pairing. The resonance is switched on by tuning the chemical potential at an electronic topological transition (ETT) near a band edge, where the Fermi surface topology of one of the subbands changes from 1D to 2D topology. We show that the tuning is realized by changing i) the misfit strain between the superconducting planes and the spacers ii) the charge density and iii) the disorder. The system is at the verge of a catastrophe i.e. near a structural and magnetic phase transition associated with the stripes (analogous to the 1/8 stripe phase in cuprates) order to disorder phase transition. Fine tuning of both the chemical potential and the disorder pushes the critical temperature Ts of this phase transition to zero giving a quantum critical point. Here the quantum lattice and magnetic fluctuations promote the Feshbach resonance of the exchange-like anisotropic pairing. This superconducting phase that resists to the attacks of temperature is shown to be controlled by the interplay of the hopping energy between stripes and the quantum fluctuations. The superconducting gaps in the multiple Fermi surface spots reported by the recent ARPES experiment of D. V. Evtushinsky et al. arXiv:0809.4455 are shown to support the Feshbach scenario.Comment: 31 pages, 7 figure