Understanding the Origins of Bacterial Resistance to Aminoglycosides through Molecular Dynamics Mutational Study of the Ribosomal A-Site

Paromomycin is an aminoglycosidic antibiotic that targets the RNA of the bacterial small ribosomal subunit. It binds in the A-site, which is one of the three tRNA binding sites, and affects translational fidelity by stabilizing two adenines (A1492 and A1493) in the flipped-out state. Experiments have shown that various mutations in the A-site result in bacterial resistance to aminoglycosides. In this study, we performed multiple molecular dynamics simulations of the mutated A-site RNA fragment in explicit solvent to analyze changes in the physicochemical features of the A-site that were introduced by substitutions of specific bases. The simulations were conducted for free RNA and in complex with paromomycin. We found that the specific mutations affect the shape and dynamics of the binding cleft as well as significantly alter its electrostatic properties. The most pronounced changes were observed in the U1406C∶U1495A mutant, where important hydrogen bonds between the RNA and paromomycin were disrupted. The present study aims to clarify the underlying physicochemical mechanisms of bacterial resistance to aminoglycosides due to target mutations

Chemical, functional, and structural properties of spent coffee grounds and coffee silverskin

Spent coffee grounds (SCG) and coffee silverskin (CS) represent a great pollution hazard if discharged into the environment. Taking this fact into account, the purpose of this study was to evaluate the chemical composition, functional properties, and structural characteristics of these agro-industrial residues in order to identify the characteristics that allow their reutilization in industrial processes. According to the results, SCG and CS are both of lignocellulosic nature. Sugars polymerized to their cellulose and hemicellulose fractions correspond to 51.5 and 40.45 % w/w, respectively; however, the hemicellulose sugars and their composition significantly differ from one residue to another. SCG and CS particles differ in terms of morphology and crystallinity, but both materials have very low porosity and similar melting point. In terms of functional properties, SCG and CS present good water and oil holding capacities, emulsion activity and stability, and antioxidant potential, being therefore great candidates for use on food and pharmaceutical fields.The authors acknowledge the financial support of the Science and Technology Foundation of Portugal (FCT) through the grant SFRH/BD/80948/2011 and the Strategic Project PEst-OE/EQB/LA0023/2013. The authors also thank the Project "BioInd - Biotechnology and Bioengineering for improved Industrial and Agro-Food processes", REF. NORTE-07-0124-FEDER-000028 co-funded by the Programa Operacional Regional do Norte (ON.2-O Novo Norte), QREN, FEDER. Thanks are also given to Prof. Jose J.M. Orfao, from the Department of Chemical Engineering, Universidade do Porto (Portugal), for his assistance with the porosity analyses

Space- and time-resolved investigation on diffusion kinetics of human skin following macromolecule delivery by microneedle arrays

Microscale medical devices are being developed for targeted skin delivery of vaccines and the extraction of biomarkers, with the potential to revolutionise healthcare in both developing and developed countries. The effective clinical development of these devices is dependent on understanding the macro-molecular diffusion properties of skin. We hypothesised that diffusion varied according to specific skin layers. Using three different molecular weights of rhodamine dextran (RD) (MW of 70, 500 and 2000 kDa) relevant to the vaccine and therapeutic scales, we deposited molecules to a range of depths (0–300 µm) in ex vivo human skin using the Nanopatch device. We observed significant dissipation of RD as diffusion with 70 and 500 kDa within the 30 min timeframe, which varied with MW and skin layer. Using multiphoton microscopy, image analysis and a Fick’s law analysis with 2D cartesian and axisymmetric cylindrical coordinates, we reported experimental trends of epidermal and dermal diffusivity values ranging from 1–8 µm2 s-1 to 1–20 µm2 s-1 respectively, with a significant decrease in the dermal-epidermal junction of 0.7–3 µm2 s-1. In breaching the stratum corneum (SC) and dermal-epidermal junction barriers, we have demonstrated practical application, delivery and targeting of macromolecules to both epidermal and dermal antigen presenting cells, providing a sound knowledge base for future development of skin-targeting clinical technologies in humans

A new species of cosmocercoides (Nematoda; cosmocercidae) and other helminths in leptodactylus latrans (anura; leptodactylidae) from Argentina

Cosmocercoides latrans n. sp. (Cosmocercidae) from the small intestine of Leptodactylus latrans (Anura: Leptodactylidae) from Northeastern Province of Buenos Aires, Argentina is described. The new species can be distinguished from their congeners by a combination of the characters, among which stands out the number of rosette papillae, the lack of gubernaculum and the presence of lateral alae in both sexes. There are over 20 species in the genus Cosmocercoides, and Cosmocercoides latrans n. sp. represents the third species from the Neotropical realm and the second for Argentina. Additionally, seven previously known taxa are reported; Pseudoacanthocephalus cf. lutzi, Catadiscus uruguayensis, Rauschiella palmipedis, Aplectana hylambatis, Cosmocerca parva, Schrankiana sp. and Rhabdias elegans; providing literature records and information on distribution and host-parasite relationships.Fil: Draghi, Regina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Zoología Invertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Drago, Fabiana Beatriz. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Zoología Invertebrados; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Lunaschi, Lía Inés. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Zoología Invertebrados; Argentin

Obesity prevalence from a European perspective: a systematic review

<p>Abstract</p> <p>Background</p> <p>Obesity has been recognised as an important contributing factor in the development of various diseases, but comparative data on this condition are limited. We therefore aimed to identify and discuss current epidemiological data on the prevalence of obesity in European countries.</p> <p>Methods</p> <p>We identified relevant published studies by means of a MEDLINE search (1990–2008) supplemented by information obtained from regulatory agencies. We only included surveys that used direct measures of weight and height and were representative of each country's overall population.</p> <p>Results</p> <p>In Europe, the prevalence of obesity (body mass index ≥ 30 kg/m²) in men ranged from 4.0% to 28.3% and in women from 6.2% to 36.5%. We observed considerable geographic variation, with prevalence rates in Central, Eastern, and Southern Europe being higher than those in Western and Northern Europe.</p> <p>Conclusion</p> <p>In Europe, obesity has reached epidemic proportions. The data presented in our review emphasise the need for effective therapeutic and preventive strategies.</p

Micropropagation and conservation of selected endangered anticancer medicinal plants from the Western Ghats of India

Globally, cancer is a constant battle which severely affects the human population. The major limitations of the anticancer drugs are the deleterious side effects on the quality of life. Plants play a vital role in curing many diseases with minimal or no side effects. Phytocompounds derived from various medicinal plants serve as the best source of drugs to treat cancer. The global demand for phytomedicines is mostly reached by the medicinal herbs from the tropical nations of the world even though many plant species are threatened with extinction. India is one of the mega diverse countries of the world due to its ecological habitats, latitudinal variation, and diverse climatic range. Western Ghats of India is one of the most important depositories of endemic herbs. It is found along the stretch of south western part of India and constitutes rain forest with more than 4000 diverse medicinal plant species. In recent times, many of these therapeutically valued herbs have become endangered and are being included under the red-listed plant category in this region. Due to a sharp rise in the demand for plant-based products, this rich collection is diminishing at an alarming rate that eventually triggered dangerous to biodiversity. Thus, conservation of the endangered medicinal plants has become a matter of importance. The conservation by using only in situ approaches may not be sufficient enough to safeguard such a huge bio-resource of endangered medicinal plants. Hence, the use of biotechnological methods would be vital to complement the ex vitro protection programs and help to reestablish endangered plant species. In this backdrop, the key tools of biotechnology that could assist plant conservation were developed in terms of in vitro regeneration, seed banking, DNA storage, pollen storage, germplasm storage, gene bank (field gene banking), tissue bank, and cryopreservation. In this chapter, an attempt has been made to critically review major endangered medicinal plants that possess anticancer compounds and their conservation aspects by integrating various biotechnological tool

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700