Aldobiouronic acid domains in Helicobacter pylori

Helicobacter pylori cell-surface glycans exert strong influences in host–microbe interplays and define the strain’s immunological signature. Envisaging the development of a carbohydrate-based vaccine against the gastroduodenal pathogen H. pylori, several clinical isolates are being screened for their cell-surface glycan profile. The present work concerns H. pylori clinical specimen PTAV79 that abundantly expressed amylose-like glycans. These polysaccharides were isolated in glycan-rich fractions resultant from phenol–water extractions and purified by Bio-Gel P2. Structural studies showed that the glycans are linked to glycerol and present aldobiouronic acid domains composed of [→3)-α-d-GlcA-(1→4)-α-d-Glc-(1→] repeating units. The amylose domains were constituted by an average of 19 Glc residues and the acidic moieties had an average number of 10 aldobiouronic acid repeating units. These polysaccharides were isolated in fractions that, although hydrophilic, were rich in stearic acid, strongly suggesting that they are present as glycerolipids anchored to cell-surface.     

Sodium hyaluronate/chitosan polyelectrolyte complex scaffolds for dental pulp regeneration: synthesis and characterization

In the present study, small-sized porous scaffolds were obtained from the freeze-drying of sodium hyaluronate/chitosan polyelectrolyte complexes. The obtained materials were characterized by a set of techniques including attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, swelling determination and weight loss studies. The morphology of the scaffolds was observed using scanning electron microscopy. Thermal characterization of the scaffolds was also performed by dynamic mechanical thermal analysis and thermogravimetric analysis. Finally, the cytotoxic profile of the prepared scaffolds was evaluated in vitro, using mesenchymal stem cells. The results obtained showed that cells adhered to scaffolds and proliferated. This study also confirmed that the degradation by-products of sodium hyaluronate/chitosan scaffold are noncytotoxic, which is fundamental for its application in the biomedical field.     

Wound infection by multiresistant Staphylococcus sciuri identified by molecular methods

We describe a case of wound infection by multidrug-resistant Staphylococcus sciuri in a patient admitted to hospital for injuries in Agreste Alagoas, Brazil, identified through broad-spectrum PCR and sequencing of 16S rDNA gene. Due to its high resistance profile, the infection was characterized as methicillin-resistant Staphylococcus presenting sensitive only to vancomycin and chloramphenicol. The injury resulting from trauma associated with infection resulted in amputation of the infected limb.     

Esophageal cancer related gene-4 is a choroid plexus-derived injury response gene: evidence for a biphasic response in early and late brain injury

By virtue of its ability to regulate the composition of cerebrospinal fluid (CSF), the choroid plexus (CP) is ideally suited to instigate a rapid response to traumatic brain injury (TBI) by producing growth regulatory proteins. For example, Esophageal Cancer Related Gene-4 (Ecrg4) is a tumor suppressor gene that encodes a hormone-like peptide called augurin that is present in large concentrations in CP epithelia (CPe). Because augurin is thought to regulate senescence, neuroprogenitor cell growth and differentiation in the CNS, we evaluated the kinetics of Ecrg4 expression and augurin immunoreactivity in CPe after CNS injury. Adult rats were injured with a penetrating cortical lesion and alterations in augurin immunoreactivity were examined by immunohistochemistry. Ecrg4 gene expression was characterized by in situ hybridization. Cell surface augurin was identified histologically by confocal microscopy and biochemically by sub-cellular fractionation. Both Ecrg4 gene expression and augurin protein levels were decreased 24-72 hrs post-injury but restored to uninjured levels by day 7 post-injury. Protein staining in the supraoptic nucleus of the hypothalamus, used as a control brain region, did not show a decrease of auguin immunoreactivity. Ecrg4 gene expression localized to CPe cells, and augurin protein to the CPe ventricular face. Extracellular cell surface tethering of 14 kDa augurin was confirmed by cell surface fractionation of primary human CPe cells in vitro while a 6-8 kDa fragment of augurin was detected in conditioned media, indicating release from the cell surface by proteolytic processing. In rat CSF however, 14 kDa augurin was detected. We hypothesize the initial release and proteolytic processing of augurin participates in the activation phase of injury while sustained Ecrg4 down-regulation is dysinhibitory during the proliferative phase. Accordingly, augurin would play a constitutive inhibitory function in normal CNS while down regulation of Ecrg4 gene expression in injury, like in cancer, dysinhibits proliferation.     

RedeR: R/Bioconductor package for representing modular structures, nested networks and multiple levels of hierarchical associations

Visualization and analysis of molecular networks are both central to systems biology. However, there still exists a large technological gap between them, especially when assessing multiple network levels or hierarchies. Here we present RedeR, an R/Bioconductor package combined with a Java core engine for representing modular networks. The functionality of RedeR is demonstrated in two different scenarios: hierarchical and modular organization in gene co-expression networks and nested structures in time-course gene expression subnetworks. Our results demonstrate RedeR as a new framework to deal with the multiple network levels that are inherent to complex biological systems. RedeR is available from http://bioconductor.org/packages/release/bioc/html/RedeR.html.     

FunSys: Software for functional analysis of prokaryotic transcriptome and proteome

The vast amount of data produced by next-generation sequencing (NGS) has necessitated the development of computational tools to assist in understanding the myriad functions performed by the biological macromolecules involved in heredity. In this work, we developed the FunSys programme, a stand-alone tool with an user friendly interface that enables us to evaluate and correlate differential expression patterns from RNA sequencing and proteomics datasets. The FunSys generates charts and reports based on the results of the analysis of differential expression to aid the interpretation of the results. AVAILABILITY: The database is available for free at https://sourceforge.net/projects/funsysufpa/     

Effect of the hydrostatic pressure on otolith growth of early juveniles of Nile tilapia Oreochromis niloticus

Nile tilapia Oreochromis niloticus early juveniles were maintained for 2 weeks in a pressurized system under a controlled photoperiod, at constant salinity and temperature. Groups of fish were exposed to one of three absolute hydrostatic pressure (HP) regimes: (1) a constant normal atmospheric pressure (100 kPa), (2) a constant 40 m pressure (500 kPa) or (3) a semi-diurnal cyclic vertical migration (100-500 kPa). No significant differences were detected in otolith size and incremental periodicity among the three HP treatments, suggesting that HP does not affect otolith growth of early juveniles O. niloticus.     

The global pipeline of new medicines for the control and elimination of malaria

ABSTRACT: Over the past decade, there has been a transformation in the portfolio of medicines to combat malaria. New fixed-dose artemisinin combination therapy is available, with four different types having received approval from Stringent Regulatory Authorities or the World Health Organization (WHO). However, there is still scope for improvement. The Malaria Eradication Research agenda identified several gaps in the current portfolio. Simpler regimens, such as a single-dose cure are needed, compared with the current three-day treatment. In addition, new medicines that prevent transmission and also relapse are needed, but with better safety profiles than current medicines. There is also a big opportunity for new medicines to prevent reinfection and to provide chemoprotection. This study reviews the global portfolio of new medicines in development against malaria, as of the summer of 2012. Cell-based phenotypic screening, and 'fast followers' of clinically validated classes, mean that there are now many new classes of molecules starting in clinical development, especially for the blood stages of malaria. There remain significant gaps for medicines blocking transmission, preventing relapse, and long-duration molecules for chemoprotection. The nascent pipeline of new medicines is significantly stronger than five years ago. However, there are still risks ahead in clinical development and sustainable funding of clinical studies is vital if this early promise is going to be delivered.     

Aging reverses the role of the transient receptor potential vanilloid-1 channel in systemic inflammation from anti-inflammatory to proinflammatory

Studies in young rodents have shown that the transient receptor potential vanilloid-1 (TRPV1) channel plays a suppressive role in the systemic inflammatory response syndrome (SIRS) by inhibiting production of tumor necrosis factor (TNF)α and possibly by other mechanisms. We asked whether the anti-inflammatory role of TRPV1 changes with age. First, we studied the effect of AMG517, a selective and potent TRPV1 antagonist, on aseptic, lipopolysaccharide (LPS)-induced SIRS in young (12 wk) mice. In agreement with previous studies, AMG517 increased LPS-induced mortality in the young. We then studied the effects of TRPV1 antagonism (AMG517 or genetic deletion of TRPV1) on SIRS in middle-aged (43–44 wk) mice. Both types of TRPV1 antagonism delayed and decreased LPS-induced mortality, indicating a reversal of the anti-inflammatory role of TRPV1 with aging. In addition, deletion of TRPV1 decreased the serum TNFα response to LPS, suggesting that the suppressive control of TRPV1 on TNFα production is also reversed with aging. In contrast to aseptic SIRS, polymicrobial sepsis (induced by cecal ligation and puncture) caused accelerated mortality in aged TRPV1-deficient mice as compared with wild-type littermates. The recovery of TRPV1-deficient mice from hypothermia associated with the cecal ligation and puncture procedure was delayed. Hence, the reversal of the anti-inflammatory role of TRPV1 found in the aged and their decreased systemic inflammatory response are coupled with suppressed defense against microbial infection. These results caution that TRPV1 antagonists, widely viewed as new-generation painkillers, may decrease the resistance of older patients to infection and sepsis.Key words: TRP channels, sepsis, systemic inflammation, endotoxin shock     

A Fast Incremental Gaussian Mixture Model

This work builds upon previous efforts in online incremental learning, namely the Incremental Gaussian Mixture Network (IGMN). The IGMN is capable of learning from data streams in a single-pass by improving its model after analyzing each data point and discarding it thereafter. Nevertheless, it suffers from the scalability point-of-view, due to its asymptotic time complexity of O(NKD ³) for N data points, K Gaussian components and D dimensions, rendering it inadequate for high-dimensional data. In this work, we manage to reduce this complexity to O(NKD ²) by deriving formulas for working directly with precision matrices instead of covariance matrices. The final result is a much faster and scalable algorithm which can be applied to high dimensional tasks. This is confirmed by applying the modified algorithm to high-dimensional classification datasets.