BioNanoAdhesion: atomic force microscopy study of the electrostatic properties of pyridine-and imidazole-based polycationic surfaces

Self-assembled monolayers of pyridine- and imidazole-based disulfides are currently being produced on low roughness gold surfaces. The electrostatic interaction between these surfaces and an atomic force microscope cantilever, modified with a silica microparticle, will subsequently be investigated as a function of environmental pH. The results can be used towards the development of improved nanoparticulate non-viral gene delivery vectors

Glimpses of Tribal Botanical Knowledge of Tirunelveli Hills, Western Ghats, India

In the present paper, 46 plant species of angiosperms belonging to 19 genera of Euphorbiaceae that occur naturally in the Tirunelveli Hills of western Ghats, India, were chosen for study. It was found that the uses of Euphorbiaceous plants by the inhabitants of this region cover a number of broad categories including food, various kinds of poisons, medicines, sundry types of oils, waxes, rubbers, varnishes, compounds for paints and other industrial products

Comprehensive mutational analysis of yeast DEXD/H box RNA helicases involved in large ribosomal subunit biogenesis

DEXD/H box putative RNA helicases are required for pre-rRNA processing in Saccharomyces cerevisiae, although their exact roles and substrates are unknown. To characterize the significance of the conserved motifs for helicase function, a series of five mutations were created in each of the eight essential RNA helicases (Has1, Dbp6, Dbp10, Mak5, Mtr4, Drs1, Spb4, and Dbp9) involved in 60S ribosomal subunit biogenesis. Each mutant helicase was screened for the ability to confer dominant negative growth defects and for functional complementation. Different mutations showed different degrees of growth inhibition among the helicases, suggesting that the conserved regions do not function identically in vivo. Mutations in motif I and motif II (the DEXD/H box) often conferred dominant negative growth defects, indicating that these mutations do not interfere with substrate binding. In addition, mutations in the putative unwinding domains (motif III) demonstrated that conserved amino acids are often not essential for function. Northern analysis of steady-state RNA from strains expressing mutant helicases showed that the dominant negative mutations also altered pre-rRNA processing. Coimmunoprecipitation experiments indicated that some RNA helicases associated with each other. In addition, we found that yeasts disrupted in expression of the two nonessential RNA helicases, Dbp3 and Dbp7, grew worse than when either one alone was disrupted

The Saito-Kurokawa lifting and Darmon points

Let E_{/_\Q} be an elliptic curve of conductor $Np$ with $p\nmid N$ and let $f$ be its associated newform of weight 2. Denote by $f_\infty$ the $p$-adic Hida family passing though $f$, and by $F_\infty$ its $\Lambda$-adic Saito-Kurokawa lift. The $p$-adic family $F_\infty$ of Siegel modular forms admits a formal Fourier expansion, from which we can define a family of normalized Fourier coefficients $\{\widetilde A_T(k)\}_T$ indexed by positive definite symmetric half-integral matrices $T$ of size $2\times 2$. We relate explicitly certain global points on $E$ (coming from the theory of Stark-Heegner points) with the values of these Fourier coefficients and of their $p$-adic derivatives, evaluated at weight $k=2$.Comment: 14 pages. Title change

Rescue of the MERTK phagocytic defect in a human iPSC disease model using translational read-through inducing drugs.

Inherited retinal dystrophies are an important cause of blindness, for which currently there are no effective treatments. In order to study this heterogeneous group of diseases, adequate disease models are required in order to better understand pathology and to test potential therapies. Induced pluripotent stem cells offer a new way to recapitulate patient specific diseases in vitro, providing an almost limitless amount of material to study. We used fibroblast-derived induced pluripotent stem cells to generate retinal pigment epithelium (RPE) from an individual suffering from retinitis pigmentosa associated with biallelic variants in MERTK. MERTK has an essential role in phagocytosis, one of the major functions of the RPE. The MERTK deficiency in this individual results from a nonsense variant and so the MERTK-RPE cells were subsequently treated with two translational readthrough inducing drugs (G418 & PTC124) to investigate potential restoration of expression of the affected gene and production of a full-length protein. The data show that PTC124 was able to reinstate phagocytosis of labeled photoreceptor outer segments at a reduced, but significant level. These findings represent a confirmation of the usefulness of iPSC derived disease specific models in investigating the pathogenesis and screening potential treatments for these rare blinding disorders

PHARMACOKINETICS OF SECOND LINE ANTI-TB DRUG (LEVOFLOXACIN) IN MDR-TB PATIENTS

Tuberculosis, commonly known as TB, is the world’s second deadliest disease caused by the bacterium Mycobacterium tuberculosis (MTB). The treatment for TB started in the year 1944 after the discovery of the antibiotic streptomycin. Over the century, the TB bacteria have evolved into the resistance forms, despite the use of effective drugs. In our study, We analysed the pharmacokinetic profile of Levofloxacin in MDR-TB patients. LFX is a synthetic broad spectrum antibacterial agent. It is the S-Isomer of the race mate. Plasma concentrations of levofloxacin were estimated using the validated methods by HPLC at NIRT. We had analysed the plasma concentrations of individual patients over different time intervals post single dosage. In case of LFX, about 10(40%) patients had their Cmax> 12µg/ml, 3 patients showed sub therapeutic Cmax value i.e. < 8 µg/ml and the remaining 12 patients (48%) had their Cmax value within the range. This study is expected to have important clinical implications.&nbsp

Role of cellular senescence and NOX4-mediated oxidative stress in systemic sclerosis pathogenesis.

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and numerous internal organs and a severe fibroproliferative vasculopathy resulting frequently in severe disability and high mortality. Although the etiology of SSc is unknown and the detailed mechanisms responsible for the fibrotic process have not been fully elucidated, one important observation from a large US population study was the demonstration of a late onset of SSc with a peak incidence between 45 and 54 years of age in African-American females and between 65 and 74 years of age in white females. Although it is not appropriate to consider SSc as a disease of aging, the possibility that senescence changes in the cellular elements involved in its pathogenesis may play a role has not been thoroughly examined. The process of cellular senescence is extremely complex, and the mechanisms, molecular events, and signaling pathways involved have not been fully elucidated; however, there is strong evidence to support the concept that oxidative stress caused by the excessive generation of reactive oxygen species may be one important mechanism involved. On the other hand, numerous studies have implicated oxidative stress in SSc pathogenesis, thus, suggesting a plausible mechanism in which excessive oxidative stress induces cellular senescence and that the molecular events associated with this complex process play an important role in the fibrotic and fibroproliferative vasculopathy characteristic of SSc. Here, recent studies examining the role of cellular senescence and of oxidative stress in SSc pathogenesis will be reviewed

How Do Black Holes Predict the Sign of the Fourier Coefficients of Siegel Modular Forms?

Single centered supersymmetric black holes in four dimensions have spherically symmetric horizon and hence carry zero angular momentum. This leads to a specific sign of the helicity trace index associated with these black holes. Since the latter are given by the Fourier expansion coefficients of appropriate meromorphic modular forms of Sp(2,Z) or its subgroup, we are led to a specific prediction for the signs of a subset of these Fourier coefficients which represent contributions from single centered black holes only. We explicitly test these predictions for the modular forms which compute the index of quarter BPS black holes in heterotic string theory on T^6, as well as in Z_N CHL models for N=2,3,5,7.Comment: LaTeX file, 17 pages, 1 figur

Syntaxin 16 is a master recruitment factor for cytokinesis

Recently it was shown that both recycling endosome and endosomal sorting complex required for transport (ESCRT) components are required for cytokinesis, in which they are believed to act in a sequential manner to bring about secondary ingression and abscission, respectively. However, it is not clear how either of these complexes is targeted to the midbody and whether their delivery is coordinated. The trafficking of membrane vesicles between different intracellular organelles involves the formation of soluble N-ethylmalei­mide–sensitive factor attachment protein receptor (SNARE) complexes. Although membrane traffic is known to play an important role in cytokinesis, the contribution and identity of intracellular SNAREs to cytokinesis remain unclear. Here we demonstrate that syntaxin 16 is a key regulator of cytokinesis, as it is required for recruitment of both recycling endosome–associated Exocyst and ESCRT machinery during late telophase, and therefore that these two distinct facets of cytokinesis are inextricably linked

Effective Diabetic Foot Ulcer Healing Potential of Isolated Asperesocoumarin Compound from Fungal Endophyte

Diabetes was a metabolic disorder characterized by prolonged hyperglycemia that is affecting approximately 500 million populations leading to over 5millions deaths. DM results in complications like retinopathy, nephropathy, neuropathy and especially foot ulcer that are leading to amputation and disability to majority of population. Natural products are ideal to treat the foot ulcers, and fungi serve as critical sources of the molecules that treat diabetic foot ulcers effectively. Thus this research is designed to isolate coumarin molecule from fungal endopytes and to investigate the anti-diabetic activity of Asperesocoumarin-B (Ac-B) and related healing of foot ulcers in STZ+NIC induced diabetic model. The isolated molecule showed better anti-diabetic activity in terms of lowering the blood glucose levels, oral glucose tolerance, controlling the body weight, as well as normalizing liver and kidney function parameters. The isolated molecule also showed significant normalization of antioxidant enzymes and lowering of oxidative LPO. The isolated molecule (AC-B) showed increase in wound healing of the diabetic rats in terms of reduction of the wound size over 12 days and also increase in total protein content. Histopathological studies on liver tissue and wound tissue showed significant healing and preserved tissue architecture and integrity. Healing effects were attributed in part to reduced free radical damage, the promotion of antioxidant status, the rapid deposition of collagen, and the anti-diabetic activity