Buckling and force propagation along intracellular microtubules

Motivated by recent experiments showing the compressive buckling of microtubules in cells, we study theoretically the mechanical response of and force propagation along elastic filaments embedded in a non-linear elastic medium. We find that embedded microtubules buckle when their compressive load exceeds a critical value

Polarization state of the optical near-field

The polarization state of the optical electromagnetic field lying several nanometers above complex dielectric structures reveals the intricate light-matter interaction that occurs in this near-field zone. This information can only be extracted from an analysis of the polarization state of the detected light in the near-field. These polarization states can be calculated by different numerical methods well-suited to near--field optics. In this paper, we apply two different techniques (Localized Green Function Method and Differential Theory of Gratings) to separate each polarisation component associated with both electric and magnetic optical near-fields produced by nanometer sized objects. The analysis is carried out in two stages: in the first stage, we use a simple dipolar model to achieve insight into the physical origin of the near-field polarization state. In the second stage, we calculate accurate numerical field maps, simulating experimental near-field light detection, to supplement the data produced by analytical models. We conclude this study by demonstrating the role played by the near-field polarization in the formation of the local density of states.Comment: 9 pages, 11 figures, accepted for publication in Phys. Rev.

Discrete structure of ultrathin dielectric films and their surface optical properties

The boundary problem of linear classical optics about the interaction of electromagnetic radiation with a thin dielectric film has been solved under explicit consideration of its discrete structure. The main attention has been paid to the investigation of the near-zone optical response of dielectrics. The laws of reflection and refraction for discrete structures in the case of a regular atomic distribution are studied and the structure of evanescent harmonics induced by an external plane wave near the surface is investigated in details. It is shown by means of analytical and numerical calculations that due to the existence of the evanescent harmonics the laws of reflection and refraction at the distances from the surface less than two interatomic distances are principally different from the Fresnel laws. From the practical point of view the results of this work might be useful for the near-field optical microscopy of ultrahigh resolution.Comment: 25 pages, 16 figures, LaTeX2.09, to be published in Phys.Rev.

Genetic disruption of sod1 gene causes glucose intolerance and impairs b-cell function

Oxidative stress has been associated with insulin resistance and type 2 diabetes. However, it is not clear whether oxidative damage is a cause or a consequence of the metabolic abnormalities present in diabetic subjects. The goal of this study was to determine whether inducing oxidative damage through genetic ablation of superoxide dismutase 1 (SOD1) leads to abnormalities in glucose homeostasis. We studied SOD1-null mice and wild-type (WT) littermates. Glucose tolerance was evaluated with intraperitoneal glucose tolerance tests. Peripheral and hepatic insulin sensitivity was quantitated with the euglycemic-hyperinsulinemic clamp. b-Cell function was determined with the hyperglycemic clamp and morphometric analysis of pancreatic islets. Genetic ablation of SOD1 caused glucose intolerance, which was associated with reduced in vivo b-cell insulin secretion and decreased b-cell volume. Peripheral and hepatic insulin sensitivity were not significantly altered in SOD1-null mice. High-fat diet caused glucose intolerance in WT mice but did not further worsen the glucose intolerance observed in standard chow-fed SOD1-null mice. Our findings suggest that oxidative stress per se does not play a major role in the pathogenesis of insulin resistance and demonstrate that oxidative stress caused by SOD1 ablation leads to glucose intolerance secondary to b-cell dysfunction. © 2013 by the American Diabetes Association

The clustering of galaxies at z~0.5 in the SDSS-III Data Release 9 BOSS-CMASS sample: a test for the LCDM cosmology

We present results on the clustering of 282,068 galaxies in the Baryon Oscillation Spectroscopic Survey (BOSS) sample of massive galaxies with redshifts 0.4<z<0.7 which is part of the Sloan Digital Sky Survey III project. Our results cover a large range of scales from ~0.5 to ~90 Mpc/h. We compare these estimates with the expectations of the flat LCDM cosmological model with parameters compatible with WMAP7 data. We use the MultiDark cosmological simulation together with a simple halo abundance matching technique, to estimate galaxy correlation functions, power spectra, abundance of subhaloes and galaxy biases. We find that the LCDM model gives a reasonable description to the observed correlation functions at z~0.5, which is a remarkably good agreement considering that the model, once matched to the observed abundance of BOSS galaxies, does not have any free parameters. However, we find a deviation (>~10%) in the correlation functions for scales less than ~1 Mpc/h and ~10-40 Mpc/h. A more realistic abundance matching model and better statistics from upcoming observations are needed to clarify the situation. We also estimate that about 12% of the "galaxies" in the abundance-matched sample are satellites inhabiting central haloes with mass M>~1e14 M_sun/h. Using the MultiDark simulation we also study the real space halo bias b(r) of the matched catalogue finding that b=2.00+/-0.07 at large scales, consistent with the one obtained using the measured BOSS projected correlation function. Furthermore, the linear large-scale bias depends on the number density n of the abundance-matched sample as b=-0.048-(0.594+/-0.02)*log(n/(h/Mpc)^3). Extrapolating these results to BAO scales we measure a scale-dependent damping of the acoustic signal produced by non-linear evolution that leads to ~2-4% dips at ~3 sigma level for wavenumbers k>~0.1 h/Mpc in the linear large-scale bias.Comment: Replaced to match published version. Typos corrected; 25 pages, 17 figures, 9 tables. To appear in MNRAS. Correlation functions (projected and redshift-space) and correlation matrices of CMASS presented in Appendix B. Correlation and covariance data for the combined CMASS sample can be downloaded from http://www.sdss3.org/science/boss_publications.ph

Identification of Inhibitors against Mycobacterium tuberculosis Thiamin Phosphate Synthase, an Important Target for the Development of Anti-TB Drugs

Tuberculosis (TB) continues to pose a serious challenge to human health afflicting a large number of people throughout the world. In spite of the availability of drugs for the treatment of TB, the non-compliance to 6–9 months long chemotherapeutic regimens often results in the emergence of multidrug resistant strains of Mycobacterium tuberculosis adding to the precariousness of the situation. This has necessitated the development of more effective drugs. Thiamin biosynthesis, an important metabolic pathway of M.tuberculosis, is shown to be essential for the intracellular growth of this pathogen and hence, it is believed that inhibition of this pathway would severely affect the growth of M.tuberculosis. In this study, a comparative homology model of M.tuberculosis thiamin phosphate synthase (MtTPS) was generated and employed for virtual screening of NCI diversity set II to select potential inhibitors. The best 39 compounds based on the docking results were evaluated for their potential to inhibit the MtTPS activity. Seven compounds inhibited MtTPS activity with IC50 values ranging from 20 – 100 µg/ml and two of these exhibited weak inhibition of M.tuberculosis growth with MIC99 values being 125 µg/ml and 162.5 µg/ml while one compound was identified as a very potent inhibitor of M.tuberculosis growth with an MIC99 value of 6 µg/ml. This study establishes MtTPS as a novel drug target against M.tuberculosis leading to the identification of new lead molecules for the development of antitubercular drugs. Further optimization of these lead compounds could result in more potent therapeutic molecules against Tuberculosis

Molecular identification of adenovirus causing respiratory tract infection in pediatric patients at the University of Malaya Medical Center

<p>Abstract</p> <p>Background</p> <p>There are at least 51 adenovirus serotypes (AdV) known to cause human infections. The prevalence of the different human AdV (HAdV) serotypes varies among different regions. Presently, there are no reports of the prevalent HAdV types found in Malaysia. The present study was undertaken to identify the HAdV types associated primarily with respiratory tract infections (RTI) of young children in Malaysia.</p> <p>Methods</p> <p>Archived HAdV isolates from pediatric patients with RTI seen at the University of Malaya Medical Center (UMMC), Kuala Lumpur, Malaysia from 1999 to 2005 were used. Virus isolates were inoculated into cell culture and DNA was extracted when cells showed significant cytopathic effects. AdV partial hexon gene was amplified and the sequences together with other known HAdV hexon gene sequences were used to build phylogenetic trees. Identification of HAdV types found among young children in Malaysia was inferred from the phylograms.</p> <p>Results</p> <p>At least 2,583 pediatric patients with RTI sought consultation and treatment at the UMMC from 1999 to 2005. Among these patients, 48 (< 2%) were positive for HAdV infections. Twenty-seven isolates were recovered and used for the present study. Nineteen of the 27 (~70%) isolates belonged to HAdV species C (HAdV-C) and six (~22%) were of HAdV species B (HAdV-B). Among the HAdV-C species, 14 (~74%) of them were identified as HAdV type 1 (HAdV-1) and HAdV type 2 (HAdV-2), and among the HAdV-B species, HAdV type 3 (HAdV-3) was the most common serotype identified. HAdV-C species also was isolated from throat and rectal swabs of children with hand, foot, and mouth disease (HFMD). Two isolates were identified as corresponding to HAdV-F species from a child with HFMD and a patient with intestinal obstruction.</p> <p>Conclusions</p> <p>HAdV-1 and HAdV-2 were the most common HAdV isolated from pediatric patients who sought treatment for RTI at the UMMC from 1999 to 2005. HAdV-B, mainly HAdV-3, was recovered from ~22% of the patients. These findings provide a benchmark for future studies on the prevalence and epidemiology of HAdV types in Malaysia and in the region.</p

The Vitamin B1 Metabolism of Staphylococcus aureus Is Controlled at Enzymatic and Transcriptional Levels

Vitamin B1 is in its active form thiamine pyrophosphate (TPP), an essential cofactor for several key enzymes in the carbohydrate metabolism. Mammals must salvage this crucial nutrient from their diet in order to complement the deficiency of de novo synthesis. In the human pathogenic bacterium Staphylococcus aureus, two operons were identified which are involved in vitamin B1 metabolism. The first operon encodes for the thiaminase type II (TenA), 4-amino-5-hydroxymethyl-2-methylpyrimidine kinase (ThiD), 5-(2-hydroxyethyl)-4-methylthiazole kinase (ThiM) and thiamine phosphate synthase (ThiE). The second operon encodes a phosphatase, an epimerase and the thiamine pyrophosphokinase (TPK). The open reading frames of the individual operons were cloned, their corresponding proteins were recombinantly expressed and biochemically analysed. The kinetic properties of the enzymes as well as the binding of TPP to the in vitro transcribed RNA of the proposed operons suggest that the vitamin B1 homeostasis in S. aureus is strongly regulated at transcriptional as well as enzymatic levels

Function of von Willebrand factor after crossed bone marrow transplantation between normal and von Willebrand disease pigs: effect on arterial thrombosis in chimeras.

von Willebrand factor (vWF) is essential for the induction of occlusive thrombosis in stenosed and injured pig arteries and for normal hemostasis. To separate the relative contribution of plasma and platelet vWF to arterial thrombosis, we produced chimeric normal and von Willebrand disease pigs by crossed bone marrow transplantation; von Willebrand disease (vWD) pigs were engrafted with normal pig bone marrow and normal pigs were engrafted with vWD bone marrow. Thrombosis developed in the chimeric normal pigs that showed normal levels of plasma vWF and an absence of platelet vWF; but no thrombosis occurred in the chimeric vWD pigs that demonstrated normal platelet vWF and an absence of plasma vWF. The ear bleeding times of the chimeric pigs were partially corrected by endogenous plasma vWF but not by platelet vWF. Our animal model demonstrated that vWF in the plasma compartment is essential for the development of arterial thrombosis and that it also contributes to the maintenance of bleeding time and hemostasis

Angular Momentum of Early- and Late-type Galaxies: Nature or Nurture?

We investigate the origin, the shape, the scatter, and the cosmic evolution in the observed relationship between specific angular momentum $j_\star$ and the stellar mass $M_\star$ in early-type (ETGs) and late-type galaxies (LTGs). Specifically, we exploit the observed star-formation efficiency and chemical abundance to infer the fraction f_\rm inf of baryons that infall toward the central regions of galaxies where star formation can occur. We find f_\rm inf\approx 1 for LTGs and $\approx 0.4$ for ETGs with an uncertainty of about $0.25$ dex, consistent with a biased collapse. By comparing with the locally observed $j_\star$ vs. $M_\star$ relations for LTGs and ETGs we estimate the fraction $f_j$ of the initial specific angular momentum associated to the infalling gas that is retained in the stellar component: for LTGs we find $f_j\approx 1.11^+0.75_-0.44$, in line with the classic disc formation picture; for ETGs we infer $f_j\approx 0.64^+0.20_-0.16$, that can be traced back to a $z<1$ evolution via dry mergers. We also show that the observed scatter in the $j_\star$ vs. $M_\star$ relation for both galaxy types is mainly contributed by the intrinsic dispersion in the spin parameters of the host dark matter halo. The biased collapse plus mergers scenario implies that the specific angular momentum in the stellar components of ETG progenitors at $z\sim 2$ is already close to the local values, in pleasing agreement with observations. All in all, we argue such a behavior to be imprinted by nature and not nurtured substantially by the environment