Structural Changes in Dengue Virus When Exposed to a Temperature of 37°C

Previous binding studies of antibodies that recognized a partially or fully hidden epitope suggest that insect cell-derived dengue virus undergoes structural changes at an elevated temperature. This was confirmed by our cryo-electron microscopy images of dengue virus incubated at 37°C, where viruses change their surface from smooth to rough. Here we present the cryo-electron microscopy structures of dengue virus at 37°C. Image analysis showed four classes of particles. The three-dimensional (3D) map of one of these classes, representing half of the imaged virus population, shows that the E protein shell has expanded and there is a hole at the 3-fold vertices. Fitting E protein structures into the map suggests that all of the interdimeric and some intradimeric E protein interactions are weakened. The accessibility of some previously found cryptic epitopes on this class of particles is discussed.     

On the limitations of standard statistical modeling in biological systems: A full Bayesian approach for biology

One of the most important scientific challenges today is the quantitative and predictive understanding of biological function. Classical mathematical and computational approaches have been enormously successful in modeling inert matter, but they may be inadequate to address inherent features of biological systems. We address the conceptual and methodological obstacles that lie in the inverse problem in biological systems modeling. We introduce a full Bayesian approach (FBA), a theoretical framework to study biological function, in which probability distributions are conditional on biophysical information that physically resides in the biological system that is studied by the scientist.     

Immunologic evaluation and validation of methods using synthetic peptides derived from Mycobacterium tuberculosis for the diagnosis of tuberculosis infection

The goal of this study was to demonstrate the usefulness of an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of pulmonary tuberculosis (PTB) and extrapulmonary TB (EPTB). This assay used 20 amino acid-long, non-overlapped synthetic peptides that spanned the complete Mycobacterium tuberculosis ESAT-6 and Ag85A sequences. The validation cohort consisted of 1,102 individuals who were grouped into the following five diagnostic groups: 455 patients with PTB, 60 patients with EPTB, 40 individuals with non-EPTB, 33 individuals with leprosy and 514 healthy controls. For the PTB group, two ESAT-6 peptides (12033 and 12034) had the highest sensitivity levels of 96.9% and 96.2%, respectively, and an Ag85A-peptide (29878) was the most specific (97.4%) in the PTB groups. For the EPTB group, two Ag85A peptides (11005 and 11006) were observed to have a sensitivity of 98.3% and an Ag85A-peptide (29878) was also the most specific (96.4%). When combinations of peptides were used, such as 12033 and 12034 or 11005 and 11006, 99.5% and 100% sensitivities in the PTB and EPTB groups were observed, respectively. In conclusion, for a cohort that consists entirely of individuals from Venezuela, a multi-antigen immunoassay using highly sensitive ESAT-6 and Ag85A peptides alone and in combination could be used to more rapidly diagnose PTB and EPTB infection.     

Callus induction and shoot organogenesis from anther cultures of Curcuma attenuata Wall

Curcuma attenuata is a highly valued ornamental. This study provides the first report on C. attenuata shoot organogenesis and plant regeneration. Immature anthers derived from 5 to 7?cm long inflorescences were isolated and cultured on different variations of Murashige and Skoog (MS) media to induce callus and then shoot organogenesis. When the 2-mm long anthers in which microspores were at the uninucleate developmental stage were cultured in the dark on MS medium containing 13.6???M 2,4-dichlorophenoxyacetic acid (2,4-D) and 2.3???M kinetin (KT) for 15?days and then transferred to 40???mol?m^?2?s^?1 fluorescent light for 30?days, the percentage callus induction reached 33.3?%. After callus was transferred to various differentiation media and cultured in the light, 33.1?% of all callus cultures could differentiate into adventitious shoots on MS medium supplemented with 22.0???M 6-benzyladenine (BA), 0.53???M ??-naphthaleneacetic acid (NAA) and 1.4???M thidiazuron (TDZ) after culturing for 60?days. Over 95?% of plantlets survived after transplanting plantlets into trays with a mixture of sand and perlite (2: 1) for 20?days. Chromosome number, determined from the root tips of young plantlets, indicated that all plantlets were diploid (2n?=?84).     

Preliminary data on elasmobranch gillnet fishery in the Gulf of Gabès,Tunisia

Elasmobranchs are an important catch component in Tunisian artisanal fisheries. Generally, species‐specific information is largely unavailable for artisanal fisheries; an increase in knowledge thereof is essential to ensure proper management of these species. The study analyzed the gillnet fishery elasmobranch catches in the Gulf of Gabès, whereby 45 fishing trips were conducted from April to June 2007 and 2008 for the capture of a total of six species: three Rajiformes and three Carchariniformes. Rhinobatos cemiculus was the most important species (52%; 4.588 ind km^?2 net per day). Among shark species, Mustelus mustelus was the most important (66.8%; 2.21 ind km^?2 net per day). Discards represented 6.87% of total catch in weight and 14.28% in number of specimens caught. Size composition of captures varied by species, but usually mature, mainly gravid females were abundant. Further investigations are needed to obtain more information on such fragile species for the development of protective measures.     

Reproductive measures and chick provisioning of Cory's Shearwater Calonectris diomedea borealis in the Azores

Capsule Timing of breeding influenced wing-length at fledging, and egg size may be an indicator of fledging weight and the amount of food received by chicks.

Aims To investigate chick growth, temporal patterns of chick food provisioning and the importance of indices of parental condition or quality, egg size and hatching date, to predict nestling body mass and wing-length at fledging, and compare breeding and chick feeding characteristics between colonies in the northeast Atlantic.

Methods A survey of Cory's Shearwater nests was carried out at Vila islet. A sample of 52 chicks, ringed and weighed at hatching, was selected to study chick growth and food provisioning.

Results Hatching success (51%) was much lower than fledging success (87%). Both hatching date and egg size contributed to explain wing-length at fledging, but hatching date, which was negatively correlated with wing-length at fledging, had the most important contribution (22%). There was some indication that egg size may explain variation in fledging weight and the amount of food received by chicks. Food delivery and feeding frequency of chicks varied throughout the chick development stage and three phases were distinguished: (1) 0–29 days, the highest feeding frequency values and a linear increase in food delivery; (2) 30–69 days, an oscillation in food delivery and medium feeding frequencies; (3) 70–90+ days, a sharp decrease in both food delivery and feeding frequency.

Conclusion Variation in food availability did not seem sufficient to override the overall importance of indices of parental quality in determining reproductive measures and chick provisioning. Breeding and feeding characteristics were similar between colonies in the northeast Atlantic, with variability in chick provisioning higher further south.     

The emergence of neural activity and its role in the development of the enteric nervous system

The enteric nervous system (ENS) is a vital part of the autonomic nervous system that regulates many gastrointestinal functions, including motility and secretion. All neurons and glia of the ENS arise from neural crest-derived cells that migrate into the gastrointestinal tract during embryonic development. It has been known for many years that a subpopulation of the enteric neural crest-derived cells expresses pan-neuronal markers at early stages of ENS development. Recent studies have demonstrated that some enteric neurons exhibit electrical activity from as early as E11.5 in the mouse, with further maturation of activity during embryonic and postnatal development. This article discusses the maturation of electrophysiological and morphological properties of enteric neurons, the formation of synapses and synaptic activity, and the influence of neural activity on ENS development.     

Molecular detection of Leishmania infection in sand flies in border line of Iran–Turkmenistan: Restricted and permissive vectors

A molecular study was carried out to incriminate sand fly vectors of cutaneous leishmaniasis (CL) in rural areas of Sarakhs district, Khorassane-Razavi Province, northeastern Iran, in 2011. Sand flies of Sergentomyia with three species and Phlebotomus with six species respectively comprised 73.3% and 26.7% of the specimens. Phlebotomus papatasi was the most common Phlebotomine species in outdoor and indoor resting places. Leishmania infection was found at least in 17 (22%) specimens including Ph. papatasi (n = 9 pool samples), Phlebotomus caucasicus (n = 6), Phlebotomus alexandri (n = 1), and Sergentomyia sintoni (n = 1). The parasites were found comprised Leishmania major (n = 5), Leishmania turanica (n = 10), and Leishmania gerbilli (n = 4). Infection of Ph. papatasi with both L. major and L. turanica supporting the new suggestion indicating that it is not restricted only with L. major. Circulation of L. major by Ph. alexandri, and both L. gerbilli and L. turanica by Ph. caucasicus, in addition to previous data indicating the ability of Ph. alexandri to circulate Leishmania infantum and Leishmania donovani, and Ph. caucasicus to circulate L. major, suggests that these two species can be permissive vectors. The results suggest that Ph. papatasi and Ph. alexandri are the primary and secondary vectors of CL where circulating L. major between human and reservoirs, whereas Ph. caucasicus is circulating L. turanica and L. gerbilli between the rodents in the region.     

Discovery and SAR of PF-4693627, a potent,selective and orally bioavailable mPGES-1 inhibitor for the potential treatment of inflammation

Inhibition of mPGES-1, the terminal enzyme in the arachidonic acid/COX pathway to regulate the production of pro-inflammatory prostaglandin PGE2, is considered an attractive new therapeutic target for safe and effective anti-inflammatory drugs. The discovery of a novel series of orally active, selective benzoxazole piperidinecarboxamides as mPGES-1 inhibitors is described. Structure–activity optimization of lead 5 with cyclohexyl carbinols resulted in compound 12, which showed excellent in vitro potency and selectivity against COX-2, and reasonable pharmacokinetic properties. Further SAR studies of the benzoxazole ring substituents lead to a novel series of highly potent compounds with improved PK profile, including 23, 26, and 29, which were effective in a carrageenan-stimulated guinea pig air pouch model of inflammation. Based on its excellent in vitro and in vivo pharmacological, pharmacokinetic and safety profile and ease of synthesis, compound 26 (PF-4693627) was advanced to clinical studies.     

Interaction of a peptide corresponding to the loop domain of the S2 SARS-CoV virus protein with model membranes

The severe acute respiratory syndrome coronavirus (SARS-CoV) envelope spike (S) glycoprotein is responsible for the fusion between the membranes of the virus and the target cell. In the case of the S2 domain of protein S, it has been found a highly hydrophobic and interfacial domain flanked by the heptad repeat 1 and 2 regions; significantly, different peptides pertaining to this domain have shown a significant leakage effect and an important plaque formation inhibition, which, similarly to HIV-1 gp41, support the role of this region in the fusion process. Therefore, we have carried out a study of the binding and interaction with model membranes of a peptide corresponding to segment 1073–1095 of the SARS-CoV S glycoprotein, peptide SARS_L in the presence of different membrane model systems, as well as the structural changes taking place in both the lipid and the peptide induced by the binding of the peptide to the membrane. Our results show that SARS_L strongly partitions into phospholipid membranes and organizes differently in lipid environments, displaying membrane activity modulated by the lipid composition of the membrane. These data would support its role in SARS-CoV mediated membrane fusion and suggest that the region where this peptide resides could be involved in the merging of the viral and target cell membranes.