Dynamics of clusters: From elementary to biological structures

Between isolated atoms or molecules and bulk materials there lies a class of unique structures, known as clusters, that consist of a few to hundreds of atoms or molecules. Within this range of "nanophase," many physical and chemical properties of the materials evolve as a function of cluster size, and materials may exhibit novel properties due to quantum confinement effects. Understanding these phenomena is in its own rights fundamental, but clusters have the additional advantage of being controllable model systems for unraveling the complexity of condensed-phase and biological structures, not to mention their vanguard role in defining nanoscience and nanotechnology. Over the last two decades, much progress has been made, and this short overview highlights our own involvement in developing cluster dynamics, from the first experiments on elementary systems to model systems in the condensed phase, and on to biological structures

Heavy Metals Concentration in Rhizosphere and Tissues of Smooth Pigweed (A. hybridus) and Bush Okra (C. olitorius) cultivated on an Abandoned Dumpsite

The study assessed the concentrations of Pb, Cr, and Cd in rhizosphere and tissues of A. hybridus and C. olitorius grown on a dumpsite converted to farmland by plant and 0-15 cm depth soil samples which were air-dried, digested and analysed using Atomic Absorption Spectrophotometry. Some physiochemical parameters that affect transport of soil nutrients into plant tissues were analysed using standard methods. The pH of the rhizosphere soil of C. olitorius was 6.71 and the soil of A. hybridus was slightly alkaline in nature with pH 7.75. The rhizosphere of A. hybridus had the highest concentration of Pb (123.20±90.04 mg/kg) and Cd (0.63±0.63 mg/kg) while Cr was highest in the rhizosphere of C. olitorius (36.57±8.61 mg/kg). The result showed total and bioavailable metal concentrations in the soils were in the order of Pb > Cr > Cd. The order of metal uptake varied with vegetable crop. Metal concentration in tissues of A. hybridus followed the order of Pb > Cr > Cd while C. olitorius was Cr > Pb > Cd. Concentrations of Cd, Pb and Cr exceeded the maximum permissible limit in soil and within allowable limit in the tissue. C. olitorius had transfer factor (TF) < 1 for Cd, Pb and Cr. A. hybridus had similar transfer factor except for Cr with TF > 1. The study concluded that the dumpsite converted to farmland is highly contaminated with Pb, Cr, and Cd and highly accumulated by the vegetables.Keywords: Heavy metals, dumpsite, Transfer factor, vegetables

Relationship between age, radiographic normal heart size and cardio-thoracic ratio in a Nigerian population

Background: Cardio-vascular disease (CVD) is now on the increase. The precise diagnosis of CVD is of immense clinical importance to the cardiac surgeons, pathologist and also for cardiologists. However, information on normal values for various cardio-vascular structures in Nigeria, a country with the highest population of blacks in the world is sparse. In this regard the age-related radiographic sizes of a Nigerian cohort of patients with non-cardiogenic complaints or consultations were therefore assessed.Objectives: To evaluate the limits of normal cardiac size in our environment , determine if there was a relationship between the age and size of the heart and to evaluate the relationship between sex and cardiac size and cardio-thoracic ratio.Design: A cross-sectional study.Setting: The Radiology department of University of Ilorin Teaching Hospital, Ilorin, North Central Nigeria between January to June 2012.Subjects: One Hundred patients were consecutively recruited and their chest radiographs examined after fulfilling the inclusion criteria.Results: Males accounted for 55% of the study population. The age range was 1 month to 73 years, (Mean = 29.3, SD =2.41668). The mean cardiac size was 11.7cm. The average cardiac size for adult males and females, were 11.6cm and 11.5cm respectively while that of thoracic size was 29.0cm and 26.8cm respectively. Correlation between age and cardiac size was 0.66; age and thoracic size was 0.64 and between cardiac size and thoracic size was 0.89. The paired sample t-test for age and cardiac size was less than 0.05 (p value <0.05).Conclusion: knowing the average values of cardiac size for adult males and females (11.6cm and 11.5cm) and thoracic size (29.0cm and 26.8cm) respectively from this study presents a base line for early detection of variation from normal cardiac measurements in this environment

The Top Window for dark matter

We investigate a scenario that the top quark is the only window to the dark matter particle. We use the effective Lagrangian approach to write down the interaction between the top quark and the dark matter particle. Requiring the dark matter satisfying the relic density we obtain the size of the effective interaction. We show that the scenario can be made consistent with the direct and indirect detection experiments by adjusting the size of the effective coupling. Finally, we calculate the production cross section for $t\bar t + \chi \bar \chi$ at the Large Hadron Collider (LHC), which will give rise to an interesting signature of a top-pair plus large missing energy.Comment: 17 pages including 8 figures; added references and a footnot

5-Methoxybenzothiophene-2-Carboxamides as Inhibitors of Clk1/4: Optimization of Selectivity and Cellular Potency

Clks have been shown by recent studies to be promising targets for cancer therapy, as they are considered key regulators in the process of pre-mRNA splicing, which in turn affects every aspect of tumor biology. In particular, Clk1 and -4 are overexpressed in several human tumors. Most of the potent Clk1 inhibitors reported in the literature are non-selective, mainly showing off-target activity towards Clk2, Dyrk1A and Dyrk1B. Herein, we present new 5-methoxybenzothiophene2-carboxamide derivatives with unprecedented selectivity. In particular, the introduction of a 3,5- difluoro benzyl extension to the methylated amide led to the discovery of compound 10b (cell-free IC50 = 12.7 nM), which was four times more selective for Clk1 over Clk2 than the previously published flagship compound 1b. Moreover, 10b showed an improved growth inhibitory activity with T24 cells (GI50 = 0.43 µM). Furthermore, a new binding model in the ATP pocket of Clk1 was developed based on the structure-activity relationships derived from new rigidified analogues

Synergistic Anti-MRSA Activity of Cationic Nanostructured Lipid Carriers in Combination With Oxacillin for Cutaneous Application

Nanoparticles have become a focus of interest due to their ability as antibacterial agents. The aim of this study was to evaluate the anti-methicillin-resistant Staphylococcus aureus (MRSA) activity of cationic nanostructured lipid carriers (NLC) combined with oxacillin against ATCC 33591 and clinical isolate. The cationic resource on the NLC surface was soyaethyl morpholinium ethosulfate (SME). NLC loaded with oxacillin was produced to assess the antibacterial activity and the effectiveness of topical application for treating cutaneous infection. The hydrodynamic diameter and zeta potential of oxacillin-loaded NLC were 177 nm and 19 mV, respectively. When combined with NLC, oxacillin exhibited synergistic MRSA eradication. After NLC encapsulation, the minimum bactericidal concentration (MBC) of oxacillin decreased from 250 to 62.5 μg/ml. The combined NLC and oxacillin reduced the MRSA biofilm thickness from 31.2 to 13.0 μm, which was lower than the effect of NLC (18.2 μm) and antibiotic (25.2 μm) alone. The oxacillin-loaded NLC showed significant reduction in the burden of intracellular MRSA in differentiated THP-1 cells. This reduction was greater than that achieved with individual treatment. The mechanistic study demonstrated the ability of cationic NLC to disrupt the bacterial membrane, leading to protein leakage. The cell surface disintegration also increased oxacillin delivery into the cytoplasm, activating the bactericidal process. Topical NLC treatment of MRSA abscess in the skin decreased the bacterial load by log 4 and improved the skin’s architecture and barrier function. Our results demonstrated that a combination of nanocarriers and an antibiotic could synergistically inhibit MRSA growth

Saudi SCD patients’ symptoms and quality of life relative to the number of ED visits

Background Individuals living with sickle cell disease (SCD) have significantly increased emergency department (ED) use compared to the general population. In Saudi Arabia, health care is free for all individuals and therefore has no bearing on increased ED visits. However, little is known about the relationship between quality of life (QoL) and frequency of acute care utilization in this patient population. Methods A cross-sectional study was conducted on 366 patients with SCD who attended the outpatient department at King Fahad Hospital, Hofuf, Saudi Arabia. Data were collected through self-administered surveys, which included: demographics, SCD-related ED visits, clinical issues, and QoL levels. We assessed the ED use by asking for the number of SCD-related ED visits within a 6-month period. Results The self-report survey of ED visits was completed by 308 SCD patients. The median number of SCD-related ED visits within a 6-month time period (IQR) was four (2-7 visits). According to the unadjusted negative binomial model, the rate of SCD-related ED visits increased by (46, 39.3, 40, and 53.5 %) for patients with fever, skin redness with itching, swelling, and blood transfusion, respectively. Poor QoL tends to increase the rate of SCD-related ED visits. Well education and poor general health positively influenced the rate of SCD-related ED visits. Well education tends to increase the rate of SCD-related ED visits by 50.2 %. The rate of SCD-related ED visits decreased by 1.4 % for every point increase in general health. Conclusion Saudi patients with sickle cell disease reported a wide range of SCD-related ED visits. It was estimated that six of 10 SCD patients had at least three ED visits within a 6-month period. Well education and poor general health resulted in an increase in the rate of SCD-related ED visits

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Distinct Changes in cAMP and Extracellular Signal-Regulated Protein Kinase Signalling in L-DOPA-Induced Dyskinesia

Background: In rodents, the development of dyskinesia produced by L-DOPA in the dopamine-depleted striatum occurs in response to increased dopamine D1 receptor-mediated activation of the cAMP- protein kinase A and of the Rasextracellular signal-regulated kinase (ERK) signalling pathways. However, very little is known, in non-human primates, about the regulation of these signalling cascades and their association with the induction, manifestation and/or maintenance of dyskinesia. Methodology/Results: We here studied, in the gold-standard non-human primate model of Parkinson’s disease, the changes in PKA-dependent phosphorylation of DARPP-32 and GluR1 AMPA receptor, as well as in ERK and ribosomal protein S6 (S6) phosphorylation, associated to acute and chronic administration of L-DOPA. Increased phosphorylation of DARPP-32 and GluR1 was observed in both L-DOPA first-ever exposed and chronically-treated dyskinetic parkinsonian monkeys. In contrast, phosphorylation of ERK and S6 was enhanced preferentially after acute L-DOPA administration and decreased during the course of chronic treatment. Conclusion: Dysregulation of cAMP signalling is maintained during the course of chronic L-DOPA administration, while abnormal ERK signalling peaks during the initial phase of L-DOPA treatment and decreases following prolonged exposure

Anti-malarial activity of Holarrhena antidysenterica and Viola canescens, plants traditionally used against malaria in the Garhwal region of north-west Himalaya

<p>Abstract</p> <p>Background</p> <p>The increasing number of multidrug-resistant <it>Plasmodium </it>strains warrants exploration of new anti-malarials. Medicinal plant research has become more important, particularly after the development of Chinese anti-malarial drug artemisnin from <it>Artemisia annua</it>. The present study shows evaluation of anti-malarial effects of two plants commonly used against malaria in the Garhwal region of north-west Himalaya, in order to discover the herbal-based medicine.</p> <p>Methods</p> <p><it>In vitro </it>anti-plasmodial sensitivity of plant extracts was assessed using schizont maturation and parasite lactate dehydrogenase (pLDH) assay. Cytotoxic activities of the examined extracts were determined on L-6 cells of rat skeletal muscle myoblast. The 4-day test for anti-malarial activity against a chloroquine sensitive <it>Plasmodium berghei </it>NK65 strain in Swiss albino mice was used for monitoring <it>in vivo </it>activity of plant extracts.</p> <p>Results</p> <p>Chloroform extract of <it>H. antidysenterica </it>(HA-2) and petroleum ether extract of <it>V. canescens </it>(VC-1) plants significantly reduced parasitaemia in <it>P. berghei </it>infected mice. The extract HA-2 showed <it>in vitro </it>anti-plasmodial activity with its IC₅₀value 5.5 μg/ml using pLDH assay and ED₅₀value 18.29 mg/kg in <it>P. berghei </it>infected Swiss albino mice. Similarly petroleum ether extract of <it>V. canescens </it>(VC-1) showed <it>in vitro </it>anti-plasmodial activity with its IC₅₀value 2.76 μg/ml using pLDH assay and ED₅₀15.8 mg/kg in <it>P. berghei </it>infected mice. The extracts coded as HA-2 at 30 mg/kg and VC-1 at 20 mg/kg exhibited parasite inhibition in mice: 73.2% and 63.0% respectively. Of these two plant extracts, petroleum ether extract of <it>V. canescens </it>was found slightly cytotoxic.</p> <p>Conclusion</p> <p>The present investigation reflects the use of these traditional medicinal plants against malaria and these plants may work as potential source in the development of variety of herbal formulations for the treatment of malaria.</p