Mapping the unconventional orbital texture in topological crystalline insulators

The newly discovered topological crystalline insulators (TCIs) harbor a complex band structure involving multiple Dirac cones. These materials are potentially highly tunable by external electric field, temperature or strain and could find future applications in field-effect transistors, photodetectors, and nano-mechanical systems. Theoretically, it has been predicted that different Dirac cones, offset in energy and momentum-space, might harbor vastly different orbital character, a unique property which if experimentally realized, would present an ideal platform for accomplishing new spintronic devices. However, the orbital texture of the Dirac cones, which is of immense importance in determining a variety of materials properties, still remains elusive in TCIs. Here, we unveil the orbital texture in a prototypical TCI Pb$_{1-x}$Sn$_x$Se. By using Fourier-transform (FT) scanning tunneling spectroscopy (STS) we measure the interference patterns produced by the scattering of surface state electrons. We discover that the intensity and energy dependences of FTs show distinct characteristics, which can directly be attributed to orbital effects. Our experiments reveal the complex band topology involving two Lifshitz transitions and establish the orbital nature of the Dirac bands in this new class of topological materials, which could provide a different pathway towards future quantum applications

Clinical correlation of nonalcoholic fatty liver disease in a Chinese taxi drivers population in Taiwan: Experience at a teaching hospital

<p>Abstract</p> <p>Background</p> <p>To explore any gender-related differences in the prevalence of conditions-associated with non-alcoholic fatty liver disease (NAFLD) among Taiwanese taxi drivers in Taipei, Taiwan.</p> <p>Methods</p> <p>We studied 1635 healthy taxi drivers (1541 males and 94 females) who volunteered for physical check-ups in 2006. Blood samples and ultrasound fatty liver sonography results were collected.</p> <p>Results</p> <p>The prevalence of NAFLD was 66.4% and revealed no statistically significant decrease with increasing age (p = 0.58). Males exhibited a greater prevalence of NAFLD than did females (67.5% vs 47.9%, p < 0.0001). Gender-related differences for associated factors were found. For males, hypertension, hyperuricemia, higher AST, higher ALT, hypertriglyceridemia, and higher fasting plasma glucose were significantly related to NAFLD. These conditions were not sigfinicantly related to NAFLD in females.</p> <p>Conclusion</p> <p>Several gender-related differences were noted for NAFLD among Taiwanese taxi drivers.</p

Serological Evidence of Subclinical Transmission of the 2009 Pandemic H1N1 Influenza Virus Outside of Mexico

Background: Relying on surveillance of clinical cases limits the ability to understand the full impact and severity of an epidemic, especially when subclinical cases are more likely to be present in the early stages. Little is known of the infection and transmissibility of the 2009 H1N1 pandemic influenza (pH1N1) virus outside of Mexico prior to clinical cases being reported, and of the knowledge pertaining to immunity and incidence of infection during April-June, which is essential for understanding the nature of viral transmissibility as well as for planning surveillance and intervention of future pandemics. Methodology/Principal Findings: Starting in the fall of 2008, 306 persons from households with schoolchildren in central Taiwan were followed sequentially and serum samples were taken in three sampling periods for haemagglutination inhibition (HI) assay. Age-specific incidence rates were calculated based on seroconversion of antibodies to the pH1N1 virus with an HI titre of 1: 40 or more during two periods: April-June and September-October in 2009. The earliest time period with HI titer greater than 40, as well as a four-fold increase of the neutralization titer, was during April 26-May 3. The incidence rates during the pre-epidemic phase (April-June) and the first wave (July-October) of the pandemic were 14.1% and 29.7%, respectively. The transmissibility of the pH1N1 virus during the early phase of the epidemic, as measured by the effective reproductive number R(0), was 1.16 (95% confidence interval (CI): 0.98-1.34). Conclusions: Approximately one in every ten persons was infected with the 2009 pH1N1 virus during the pre-epidemic phase in April-June. The lack of age-pattern in seropositivity is unexpected, perhaps highlighting the importance of children as asymptomatic transmitters of influenza in households. Although without virological confirmation, our data raise the question of whether there was substantial pH1N1 transmission in Taiwan before June, when clinical cases were first detected by the surveillance network

Identification of Novel Susceptibility Loci for Kawasaki Disease in a Han Chinese Population by a Genome-Wide Association Study

Kawasaki disease (KD) is an acute systemic vasculitis syndrome that primarily affects infants and young children. Its etiology is unknown; however, epidemiological findings suggest that genetic predisposition underlies disease susceptibility. Taiwan has the third-highest incidence of KD in the world, after Japan and Korea. To investigate novel mechanisms that might predispose individuals to KD, we conducted a genome-wide association study (GWAS) in 250 KD patients and 446 controls in a Han Chinese population residing in Taiwan, and further validated our findings in an independent Han Chinese cohort of 208 cases and 366 controls. The most strongly associated single-nucleotide polymorphisms (SNPs) detected in the joint analysis corresponded to three novel loci. Among these KD-associated SNPs three were close to the COPB2 (coatomer protein complex beta-2 subunit) gene: rs1873668 (p = 9.52×10−5), rs4243399 (p = 9.93×10−5), and rs16849083 (p = 9.93×10−5). We also identified a SNP in the intronic region of the ERAP1 (endoplasmic reticulum amino peptidase 1) gene (rs149481, pbest = 4.61×10−5). Six SNPs (rs17113284, rs8005468, rs10129255, rs2007467, rs10150241, and rs12590667) clustered in an area containing immunoglobulin heavy chain variable regions genes, with pbest-values between 2.08×10−5 and 8.93×10−6, were also identified. This is the first KD GWAS performed in a Han Chinese population. The novel KD candidates we identified have been implicated in T cell receptor signaling, regulation of proinflammatory cytokines, as well as antibody-mediated immune responses. These findings may lead to a better understanding of the underlying molecular pathogenesis of KD

Squamocin modulates histone H3 phosphorylation levels and induces G1 phase arrest and apoptosis in cancer cells

<p>Abstract</p> <p>Background</p> <p>Histone modifications in tumorigenesis are increasingly recognized as important epigenetic factors leading to cancer. Increased phosphorylation levels of histone H3 as a result of aurora B and pMSK1 overexpression were observed in various tumors. We selected <it>aurora B </it>and <it>MSK1 </it>as representatives for testing various compounds and drugs, and found that squamocin, a bis-tetrahydrofuran annonaceous acetogenin, exerted a potent effect on histone H3 phosphorylation.</p> <p>Methods</p> <p>GBM8401, Huh-7, and SW620 cells were incubated with 15, 30, and 60 μM squamocin for 24 h. The expressions of mRNA and proteins were analyzed by qRT-PCR and Western blotting, respectively. The cell viability was determined by an MTT assay. Cell cycle distribution and apoptotic cells were analyzed by flow cytometry.</p> <p>Results</p> <p>Our results showed that squamocin inhibited the proliferation of GBM8401, Huh-7, and SW620 cells, arrested the cell cycle at the G₁phase, and activated both intrinsic and extrinsic pathways to apoptosis. In addition, we demonstrated that squamocin had the ability to modulate the phosphorylation levels of H3S10 (H3S10p) and H3S28 (H3S28p) in association with the downregulation of aurora B and pMSK1 expressions.</p> <p>Conclusions</p> <p>This study is the first to show that squamocin affects epigenetic alterations by modulating histone H3 phosphorylation at S10 and S28, providing a novel view of the antitumor mechanism of squamocin.</p

Lapatinib Induces Autophagy, Apoptosis and Megakaryocytic Differentiation in Chronic Myelogenous Leukemia K562 Cells

Lapatinib is an oral, small-molecule, dual tyrosine kinase inhibitor of epidermal growth factor receptors (EGFR, or ErbB/Her) in solid tumors. Little is known about the effect of lapatinib on leukemia. Using human chronic myelogenous leukemia (CML) K562 cells as an experimental model, we found that lapatinib simultaneously induced morphological changes resembling apoptosis, autophagy, and megakaryocytic differentiation. Lapatinib-induced apoptosis was accompanied by a decrease in mitochondrial transmembrane potential and was attenuated by the pancaspase inhibitor z-VAD-fmk, indicating a mitochondria-mediated and caspase-dependent pathway. Lapatinib-induced autophagic cell death was verified by LC3-II conversion, and upregulation of Beclin-1. Further, autophagy inhibitor 3-methyladenine as well as autophagy-related proteins Beclin-1 (ATG6), ATG7, and ATG5 shRNA knockdown rescued the cells from lapatinib-induced growth inhibition. A moderate number of lapatinib-treated K562 cells exhibited features of megakaryocytic differentiation. In summary, lapatinib inhibited viability and induced multiple cellular events including apoptosis, autophagic cell death, and megakaryocytic differentiation in human CML K562 cells. This distinct activity of lapatinib against CML cells suggests potential for lapatinib as a therapeutic agent for treatment of CML. Further validation of lapatinib activity in vivo is warranted

Functional Redundancy of Two Pax-Like Proteins in Transcriptional Activation of Cyst Wall Protein Genes in Giardia lamblia

The protozoan Giardia lamblia differentiates from a pathogenic trophozoite into an infectious cyst to survive outside of the host. During encystation, genes encoding cyst wall proteins (CWPs) are coordinately induced. Pax family transcription factors are involved in a variety of developmental processes in animals. Nine Pax proteins have been found to play an important role in tissue and organ development in humans. To understand the progression from primitive to more complex eukaryotic cells, we tried to identify putative pax genes in the G. lamblia genome and found two genes, pax1 and pax2, with limited similarity. We found that Pax1 may transactivate the encystation-induced cwp genes and interact with AT-rich initiatior elements that are essential for promoter activity and transcription start site selection. In this study, we further characterized Pax2 and found that, like Pax1, Pax2 was present in Giardia nuclei and it may specifically bind to the AT-rich initiator elements of the encystation-induced cwp1-3 and myb2 genes. Interestingly, overexpression of Pax2 increased the cwp1-3 and myb2 gene expression and cyst formation. Deletion of the C-terminal paired domain or mutation of the basic amino acids of the paired domain resulted in a decrease of nuclear localization, DNA-binding activity, and transactivation activity of Pax2. These results are similar to those found in the previous Pax1 study. In addition, the profiles of gene expression in the Pax2 and Pax1 overexpressing cells significantly overlap in the same direction and ERK1 associated complexes may phosphorylate Pax2 and Pax1, suggesting that Pax2 and Pax1 may be downstream components of a MAPK/ERK1 signaling pathway. Our results reveal functional redundancy between Pax2 and Pax1 in up-regulation of the key encystation-induced genes. These results illustrate functional redundancy of a gene family can occur in order to increase maintenance of important gene function in the protozoan organism G. lamblia

EGFR mutation detection in circulating cell-free DNA of lung adenocarcinoma patients: analysis of LUX-Lung 3 and 6

Background: In the Phase III LUX-Lung 3/6 (LL3/LL6) trials in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma patients, we evaluated feasibility of EGFR mutation detection using circulating cell-free DNA (cfDNA) and prognostic and predictive utility of cfDNA positivity (cfDNA+). Methods: Paired tumour and blood samples were prospectively collected from randomised patients. Mutations were detected using cfDNA from serum (LL3) or plasma (LL6) by a validated allele-specific quantitative real-time PCR kit. Results: EGFR mutation detection rates in cfDNA were 28.6% (serum) and 60.5% (plasma). Mutation detection in blood was associated with advanced disease characteristics, including higher performance score, number of metastatic sites and bone/liver metastases, and poorer prognosis. In patients with common EGFR mutations, afatinib improved progression-free survival vs chemotherapy in cfDNA+ (LL3: HR, 0.35; P=0.0009; LL6: HR, 0.25; P<0.0001) and cfDNA− (LL3: HR, 0.46; P<0.0001; LL6: HR, 0.12; P<0.0001) cohorts. A trend towards overall survival benefit with afatinib was observed in cfDNA+ patients. Conclusions: Plasma cfDNA is a promising alternative to biopsy for EGFR testing. Detectable mutation in blood was associated with more advanced disease and poorer prognosis. Afatinib improved outcomes in EGFR mutation-positive patients regardless of blood mutation status

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field