Strain-induced partially flat band, helical snake states, and interface superconductivity in topological crystalline insulators

Topological crystalline insulators in IV-VI compounds host novel topological surface states consisting of multi-valley massless Dirac fermions at low energy. Here we show that strain generically acts as an effective gauge field on these Dirac fermions and creates pseudo-Landau orbitals without breaking time-reversal symmetry. We predict the realization of this phenomenon in IV-VI semiconductor heterostructures, due to a naturally occurring misfit dislocation array at the interface that produces a periodically varying strain field. Remarkably, the zero-energy Landau orbitals form a flat band in the vicinity of the Dirac point, and coexist with a network of snake states at higher energy. We propose that the high density of states of this flat band gives rise to interface superconductivity observed in IV-VI semiconductor multilayers at unusually high temperatures, with non-BCS behavior. Our work demonstrates a new route to altering macroscopic electronic properties to achieve a partially flat band, and paves the way for realizing novel correlated states of matter.Comment: Accepted by Nature Physic

A comparison of host gene expression signatures associated with infection in vitro by the Makona and Ecran (Mayinga) variants of Ebola virus

The Ebola virus (EBOV) variant Makona (which emerged in 2013) was the causative agent of the largest outbreak of Ebola Virus Disease recorded. Differences in virus-host interactions between viral variants have potential consequences for transmission, disease severity and mortality. A detailed profile of the cellular changes induced by the Makona variant compared with other Ebola virus variants was lacking. In this study, A549 cells, a human cell line with a robust innate response, were infected with the Makona variant or with the Ecran variant originating from the 1976 outbreak in Central Africa. The abundance of viral and cellular mRNA transcripts was profiled using RNASeq and differential gene expression analysis performed. Differences in effects of each virus on the expression of interferon-stimulated genes were also investigated in A549 NPro cells where the type 1 interferon response had been attenuated. Cellular transcriptomic changes were compared with those induced by human respiratory syncytial virus (HRSV), a virus with a similar genome organisation and replication strategy to EBOV. Pathway and gene ontology analysis revealed differential expression of functionally important genes; including genes involved in the inflammatory response, cell proliferation, leukocyte extravasation and cholesterol biosynthesis. Whilst there was overlap with HRSV, there was unique commonality to the EBOV variants

Intervention effects of Ganoderma lucidum spores on epileptiform discharge hippocampal neurons and expression of Neurotrophin-4 and N-Cadherin

Epilepsy can cause cerebral transient dysfunctions. Ganoderma lucidum spores (GLS), a traditional Chinese medicinal herb, has shown some antiepileptic effects in our previous studies. This was the first study of the effects of GLS on cultured primary hippocampal neurons, treated with Mg2+ free medium. This in vitro model of epileptiform discharge hippocampal neurons allowed us to investigate the anti-epileptic effects and mechanism of GLS activity. Primary hippocampal neurons from <1 day old rats were cultured and their morphologies observed under fluorescence microscope. Neurons were confirmed by immunofluorescent staining of neuron specific enolase (NSE). Sterile method for GLS generation was investigated and serial dilutions of GLS were used to test the maximum non-toxic concentration of GLS on hippocampal neurons. The optimized concentration of GLS of 0.122 mg/ml was identified and used for subsequent analysis. Using the in vitro model, hippocampal neurons were divided into 4 groups for subsequent treatment i) control, ii) model (incubated with Mg2+ free medium for 3 hours), iii) GLS group I (incubated with Mg2+ free medium containing GLS for 3 hours and replaced with normal medium and incubated for 6 hours) and iv) GLS group II (neurons incubated with Mg2+ free medium for 3 hours then replaced with a normal medium containing GLS for 6 hours). Neurotrophin-4 and N-Cadherin protein expression were detected using Western blot. The results showed that the number of normal hippocampal neurons increased and the morphologies of hippocampal neurons were well preserved after GLS treatment. Furthermore, the expression of neurotrophin-4 was significantly increased while the expression of N-Cadherin was decreased in the GLS treated group compared with the model group. This data indicates that GLS may protect hippocampal neurons by promoting neurotrophin-4 expression and inhibiting N-Cadherin expression

Star forming dwarf galaxies

Star forming dwarf galaxies (SFDGs) have a high gas content and low metallicities, reminiscent of the basic entities in hierarchical galaxy formation scenarios. In the young universe they probably also played a major role in the cosmic reionization. Their abundant presence in the local volume and their youthful character make them ideal objects for detailed studies of the initial stellar mass function (IMF), fundamental star formation processes and its feedback to the interstellar medium. Occasionally we witness SFDGs involved in extreme starbursts, giving rise to strongly elevated production of super star clusters and global superwinds, mechanisms yet to be explored in more detail. SFDGs is the initial state of all dwarf galaxies and the relation to the environment provides us with a key to how different types of dwarf galaxies are emerging. In this review we will put the emphasis on the exotic starburst phase, as it seems less important for present day galaxy evolution but perhaps fundamental in the initial phase of galaxy formation.Comment: To appear in JENAM Symposium "Dwarf Galaxies: Keys to Galaxy Formation and Evolution", P. Papaderos, G. Hensler, S. Recchi (eds.). Lisbon, September 2010, Springer Verlag, in pres

Iterative sorting reveals CD133+ and CD133- melanoma cells as phenotypically distinct populations

Background: The heterogeneity and tumourigenicity of metastatic melanoma is attributed to a cancer stem cell model, with CD133 considered to be a cancer stem cell marker in melanoma as well as other tumours, but its role has remained controversial. Methods: We iteratively sorted CD133+ and CD133- cells from 3 metastatic melanoma cell lines, and observed tumourigenicity and phenotypic characteristics over 7 generations of serial xeno-transplantation in NOD/SCID mice. Results: We demonstrate that iterative sorting is required to make highly pure populations of CD133+ and CD133- cells from metastatic melanoma, and that these two populations have distinct characteristics not related to the cancer stem cell phenotype. In vitro, gene set enrichment analysis indicated CD133+ cells were related to a proliferative phenotype, whereas CD133- cells were of an invasive phenotype. However, in vivo, serial transplantation of CD133+ and CD133- tumours over 7 generations showed that both populations were equally able to initiate and propagate tumours. Despite this, both populations remained phenotypically distinct, with CD133- cells only able to express CD133 in vivo and not in vitro. Loss of CD133 from the surface of a CD133+ cell was observed in vitro and in vivo, however CD133- cells derived from CD133+ retained the CD133+ phenotype, even in the presence of signals from the tumour microenvironment. Conclusion: We show for the first time the necessity of iterative sorting to isolate pure marker-positive and marker-negative populations for comparative studies, and present evidence that despite CD133+ and CD133- cells being equally tumourigenic, they display distinct phenotypic differences, suggesting CD133 may define a distinct lineage in melanoma

Ameliorated ConA-Induced Hepatitis in the Absence of PKC-theta

Severe liver injury that occurs when immune cells mistakenly attack an individual's own liver cells leads to autoimmune hepatitis. In mice, acute hepatitis can be induced by concanavalin A (ConA) treatment, which causes rapid activation of CD1d-positive natural killer (NK) T cells. These activated NKT cells produce large amounts of cytokines, which induce strong inflammation that damages liver tissues. Here we show that PKC-θ−/− mice were resistant to ConA-induced hepatitis due to essential function of PKC-θ in NKT cell development and activation. A dosage of ConA (25 mg/kg) that was lethal to wild-type (WT) mice failed to induce death resulting from liver injury in PKC-θ−/− mice. Correspondingly, ConA-induced production of cytokines such as IFNγ, IL-6, and TNFα, which mediate the inflammation responsible for liver injury, were significantly lower in PKC-θ−/− mice. Peripheral NKT cells had developmental defects at early stages in the thymus in PKC-θ−/− mice, and as a result their frequency and number were greatly reduced. Furthermore, PKC-θ−/− bone marrow adoptively transferred to WT mice displayed similar defects in NKT cell development, suggesting an intrinsic requirement for PKC-θ in NKT cell development. In addition, upon stimulation with NKT cell-specific lipid ligand, peripheral PKC-θ−/− NKT cells produced lower levels of inflammatory cytokines than that of WT NKT cells, suggesting that activation of NKT cells also requires PKC-θ. Our results suggest PKC-θ is an essential molecule required for activation of NKT cell to induce hepatitis, and thus, is a potential drug target for prevention of autoimmune hepatitis

Treatment results for hypopharyngeal cancer by different treatment strategies and its secondary primary- an experience in Taiwan

<p>Abstract</p> <p>Purpose</p> <p>The aim of this study was to evaluate treatment results in our hypopharyngeal cancer patients.</p> <p>Patients and Methods</p> <p>A total of three hundred and ninety five hypopharyngeal cancer patients received radical treatment at our hospital; 96% were male. The majority were habitual smokers (88%), alcohol drinkers (73%) and/or betel quid chewers (51%). All patients received a CT scan or MRI for tumor staging before treatment. The stage distribution was stage I: 2 (0.5%); stage II: 22 (5.6%); stage III: 57 (14.4%) and stage IV: 314 (79.5%). Radical surgery was used first in 81 patients (20.5%), and the remaining patients (79.5%) received organ preservation-intended treatment (OPIT). In the OPIT group, 46 patients received radiotherapy alone, 156 patients received chemotherapy followed by radiotherapy (CT/RT) and 112 patients received concomitant chemo-radiotherapy (CCRT).</p> <p>Results</p> <p>The five-year overall survival rates for stages I/II, III and IV were 49.5%, 47.4% and 18.6%, respectively. There was no significant difference in overall and disease-specific survival rates between patients who received radical surgery first and those who received OPIT. In the OPIT group, CCRT tended to preserve the larynx better (p = 0.088), with three-year larynx preservation rates of 44.8% for CCRT and 27.2% for CT/RT. Thirty-seven patients developed a second malignancy, with an annual incidence of 4.6%.</p> <p>Conclusions</p> <p>There was no survival difference between OPIT and radical surgery in hypopharyngeal cancer patients at our hospital. CCRT may offer better laryngeal preservation than RT alone or CT/RT. However, prospective studies are still needed to confirm this finding. Additionally, second primary cancers are another important issue for hypopharyngeal cancer management.</p

Lithocholic Acid Is an Eph-ephrin Ligand Interfering with Eph-kinase Activation

Eph-ephrin system plays a central role in a large variety of human cancers. In fact, alterated expression and/or de-regulated function of Eph-ephrin system promotes tumorigenesis and development of a more aggressive and metastatic tumour phenotype. In particular EphA2 upregulation is correlated with tumour stage and progression and the expression of EphA2 in non-trasformed cells induces malignant transformation and confers tumorigenic potential. Based on these evidences our aim was to identify small molecules able to modulate EphA2-ephrinA1 activity through an ELISA-based binding screening. We identified lithocholic acid (LCA) as a competitive and reversible ligand inhibiting EphA2-ephrinA1 interaction (Ki = 49 µM). Since each ephrin binds many Eph receptors, also LCA does not discriminate between different Eph-ephrin binding suggesting an interaction with a highly conserved region of Eph receptor family. Structurally related bile acids neither inhibited Eph-ephrin binding nor affected Eph phosphorylation. Conversely, LCA inhibited EphA2 phosphorylation induced by ephrinA1-Fc in PC3 and HT29 human prostate and colon adenocarcinoma cell lines (IC50 = 48 and 66 µM, respectively) without affecting cell viability or other receptor tyrosine-kinase (EGFR, VEGFR, IGFR1β, IRKβ) activity. LCA did not inhibit the enzymatic kinase activity of EphA2 at 100 µM (LANCE method) confirming to target the Eph-ephrin protein-protein interaction. Finally, LCA inhibited cell rounding and retraction induced by EphA2 activation in PC3 cells. In conclusion, our findings identified a hit compound useful for the development of molecules targeting ephrin system. Moreover, as ephrin signalling is a key player in the intestinal cell renewal, our work could provide an interesting starting point for further investigations about the role of LCA in the intestinal homeostasis

The Lyman Alpha Forest in the Spectra of QSOs

Observations of redshifted Lyman alpha forest absorption in the spectra of quasistellar objects (QSOs) provide a highly sensitive probe of the distribution of gaseous matter in the universe. Over the past two decades optical spectroscopy with large ground-based telescopes, and more recently ultraviolet spectroscopy from space have yielded a wealth of information on what appears to be a gaseous, photoionized intergalactic medium, partly enriched by the products of stellar nucleosynthesis, residing in coherent structures over many hundreds of kiloparsecs. Recent progress with cosmological hydro-simulations based on hierarchical structure formation models has led to important insights into the physical structures giving rise to the forest. If these ideas are correct, a truely inter- and proto-galactic medium [at high redshift (z ~ 3), the main repository of baryons] collapses under the influence of dark matter gravity into flattened or filamentary structures, which are seen in absorption against background QSOs. With decreasing redshift, galaxies forming in the denser regions, may contribute an increasing part of the Lyman alpha absorption cross-section. Comparisons between large data samples from the new generation of telescopes and artificial Lyman alpha forest spectra from cosmological simulations promise to become a useful cosmological tool.Comment: latex plus three postscript figures, uses psfig,sty; Annual Review of Astronomy and Astrophysics 1998, vol. 36 (in press