Axonal terminals of sensory neurons and their morphological diversity

The application of electron microscopy to defining the fine structural characteristics of axon terminals and synapses was followed by a half century of intensive exploration of the molecular concomitants of synaptic activity. The summer of 2003 marks the 50th anniversary of the earliest accounts of synapses by Palay and Palade. Prompted by recent findings of specialization in the fine structure of nociceptor terminals that lack contacts remotely resembling a synapse, we present a survey of arrangements, contacts and axoplasmic contents of peripheral sensory axon terminals. The morphological principles underlying the variety of small, clear, spherical vesicles, mitochondrial aggregation, the membrane thickenings associated with sensory terminals and the organelles or inclusions associated with the site of transduction apparently do not conform to a simple parsimonious rule. It is also evident that the terminal of the central branch of bifurcated sensory axons differs structurally from its distal counterparts. This brief illustrated account addresses some important unresolved problems in the functional interpretation of the diverse morphological features exhibited in both synaptic and non-synaptic sensory axon terminals with the aim of identifying and emphasizing some key questions amenable to resolution with contemporary morphological and physiological techniques.     

Basal and antigen-induced exposure of the proline-rich sequence in CD3ε

The CD3ε cytoplasmic tail contains a conserved proline-rich sequence (PRS) that influences TCR-CD3 expression and signaling. Although the PRS can bind the SH3.1 domain of the cytosolic adapter Nck, whether the PRS is constitutively available for Nck binding or instead represents a cryptic motif that is exposed via conformational change upon TCR-CD3 engagement (CD3Δc) is currently unresolved. Furthermore, the extent to which a cis-acting CD3ε basic amino acid-rich stretch (BRS), with its unique phosphoinositide-binding capability, might impact PRS accessibility is not clear. In this study, we found that freshly harvested primary thymocytes expressed low to moderate basal levels of Nck-accessible PRS ("open-CD3"), although most TCR-CD3 complexes were inaccessible to Nck ("closed-CD3"). Ag presentation in vivo induced open-CD3, accounting for half of the basal level found in thymocytes from MHC(+) mice. Additional stimulation with either anti-CD3 Abs or peptide-MHC ligands further elevated open-CD3 above basal levels, consistent with a model wherein antigenic engagement induces maximum PRS exposure. We also found that the open-CD3 conformation induced by APCs outlasted the time of ligand occupancy, marking receptors that had been engaged. Finally, CD3ε BRS-phosphoinositide interactions played no role in either adoption of the initial closed-CD3 conformation or induction of open-CD3 by Ab stimulation. Thus, a basal level of open-CD3 is succeeded by a higher, induced level upon TCR-CD3 engagement, involving CD3Δc and prolonged accessibility of the CD3ε PRS to Nck.     

The relationship between adiponectin, ageing and renal function in a bi-ethnic sample

Ageing is associated with elevated adiponectin levels. Our aim was to assess whether age-related increase in adiponectin is associated with a decrease in renal function. The study comprised African (N=277) and Caucasian (N=326) men and women. Adiponectin levels, estimated creatinine clearance rate and obesity indices were determined. African men revealed significantly higher adiponectin levels compared to Caucasian men (p<0.01), reflecting the lower adiposity levels of the African men. No difference in obesity measures (p=0.92) and adiponectin levels (p=0.27) was observed between African and Caucasian women. A significant increase in adiponectin levels with ageing was observed in both African men and women (p<0.01). To the contrary, progressive ageing seems not to be significantly related to elevated adiponectin levels within Caucasians. Renal impairment decreased significantly within all of the groups (p<0.01). Single regression analyses performed in all specified groups revealed significant associations between adiponectin and estimated creatinine clearance, however a multiple regression model revealed that insulin resistance had the strongest association with adiponectin within all the groups. In conclusion, age-related rise in adiponectin levels observed in Africans may not be due to renal impairment.     

To compete or defend: linking functional trait variation with life-history tradeoffs in a foundation tree species

Oecologia - Although chemical deterrents to herbivory often exact costs in terms of plant growth, the manner in which those costs arise, and their physiological relationship to other functional...     

Association of Major Depressive Episode with Negative Outcomes of Tuberculosis Treatment

Background

Pulmonary tuberculosis (TB) persists an important contributor to the burden of diseases in developing countries. TB control success is based on the patient’s compliance to the treatment. Depressive disorders have been negatively associated with compliance of therapeutic schemes for chronic diseases. This study aimed to estimate the significance and magnitude of major depressive episode as a hazard factor for negative outcomes (NO), including abandon or death in patients receiving TB treatment.

Methodology/Principal Findings

A longitudinal study was conducted to evaluate the association of major depressive episode (MDE), as measured by a 5-item version of the Center for Epidemiological Studies Depression Scale (CES-D) with NO to TB treatment. Patients with confirmed TB were enrolled before the start of TB treatment. Baseline measurements included socio-demographic variables as well as the CES-D, which was also applied every month until the end of the treatment. Death and treatment default were assessed monthly. Survivor function (SF) for NO according to MDE status (CES-D≥6) at baseline (MDEb) was estimated. Cox’s Regression was performed for bivariate analyses as well as for the multivariate model. A total of 325 patients accepted to participate in the study, of which 34 where excluded for diagnosis of MDR-TB. NO was observed in 24 patients (8.2%); 109 (37%) presented MDEb. Statistically significant difference was found on the SF of patients with and without MDEb (0.85 vs. 0.96, p-value = 0.002). The hazard ratio for NO, controlled for age, sex, marital status and instruction level was 3.54 (95%CI 1.43–8.75; p-value = 0.006).

Conclusion

The presence of MDE at baseline is associated to NO of TB treatment. Targeting detection and treatment of MDE may improve TB treatment outcomes.     

BioGraph: unsupervised biomedical knowledge discovery via automated hypothesis generation

We present BioGraph, a data integration and data mining platform for the exploration and discovery of biomedical information. The platform offers prioritizations of putative disease genes, supported by functional hypotheses. We show that BioGraph can retrospectively confirm recently discovered disease genes and identify potential susceptibility genes, outperforming existing technologies, without requiring prior domain knowledge. Additionally, BioGraph allows for generic biomedical applications beyond gene discovery. BioGraph is accessible at .     

Bacteria and Archaea community structure in the rumen microbiome of goats (Capra hircus) from the semiarid region of Brazil

Most studies present in the literature about the rumen microbiome have focused on cattle and sheep. This is the first report of the characterization of the bacterial and archaeal communities present in the liquid and solid-associated fractions of the rumen from free ranging Moxotó breed goats using 16S rRNA gene libraries. PCR was used to amplify the 16S rRNA gene with bacterial and archaeal universal primers and sequences from each library constructed were obtained. Sequences of Bacteria from the phyla Bacteroidetes and Firmicutes were predominant. The overall dominant classes in the rumen were Clostridia and Bacteroidia, which are known to play a role in plant fiber degradation in other ruminants. Unclassified Bacteria accounted for 4.7% of the liquid fraction sequences and 16.4% of the solid fraction sequences. From the archaeal libraries only sequences from the phylum Euryarcheota were identified and were assigned to the class Methanobacteria of the genera Methanobrevibacter and Methanosphaera. A group of Archaea not previously known to be associated with the rumen was identified: uncultured methanogens belonging to the "uncultured marine bacteria" groups II and III. The local water contained high salt concentrations and this may explain the presence of these groups in the Moxotó goat rumen.