Lymphocyte subsets in human immunodeficiency virus-unexposed Brazilian individuals from birth to adulthood

Ethnic origin, genetics, gender and environmental factors have been shown to influence some immunologic indices, so that development of reference values for populations of different backgrounds may be necessary. We have determined the distribution of lymphocyte subsets in healthy Brazilian individuals from birth to adulthood. Lymphocyte subsets were determined using four-colour cytometry in a cross-sectional study of 463 human immunodeficiency virus-unexposed children and adults from birth through 49 years of age. Lymphocyte subsets varied according to age, as previously observed in other studies. However, total CD4+ T cell numbers were lower than what was described in the Pediatric AIDS Clinical Trials Group P1009 (PACTG P1009), which assessed an American population of predominantly African and Hispanic backgrounds until the 12-18 year age range, when values were comparable. Naïve percentages and absolute values of CD8+ T cells, as assessed by CD45RA expression, were also lower than the PACTG P1009 data for all analysed age ranges. CD38 expression on both CD4+ and CD8+ T cells was lower than the PACTG P1009 values, with a widening gap between the two studies at older age ranges. Different patterns of cell differentiation seem to occur in different settings and may have characteristic expression within each population.Universidade Federal de São Paulo (UNIFESP) Departamento de MedicinaCentro Assistencial Cruz de MaltaUniversidade Federal de São Paulo (UNIFESP) Departamento de PediatriaUNIFESP, Depto. de MedicinaUNIFESP, Depto. de PediatriaSciEL

Mapping Proprioception across a 2D Horizontal Workspace

Relatively few studies have been reported that document how proprioception varies across the workspace of the human arm. Here we examined proprioceptive function across a horizontal planar workspace, using a new method that avoids active movement and interactions with other sensory modalities. We systematically mapped both proprioceptive acuity (sensitivity to hand position change) and bias (perceived location of the hand), across a horizontal-plane 2D workspace. Proprioception of both the left and right arms was tested at nine workspace locations and in 2 orthogonal directions (left-right and forwards-backwards). Subjects made repeated judgments about the position of their hand with respect to a remembered proprioceptive reference position, while grasping the handle of a robotic linkage that passively moved their hand to each judgement location. To rule out the possibility that the memory component of the proprioceptive testing procedure may have influenced our results, we repeated the procedure in a second experiment using a persistent visual reference position. Both methods resulted in qualitatively similar findings. Proprioception is not uniform across the workspace. Acuity was greater for limb configurations in which the hand was closer to the body, and was greater in a forward-backward direction than in a left-right direction. A robust difference in proprioceptive bias was observed across both experiments. At all workspace locations, the left hand was perceived to be to the left of its actual position, and the right hand was perceived to be to the right of its actual position. Finally, bias was smaller for hand positions closer to the body. The results of this study provide a systematic map of proprioceptive acuity and bias across the workspace of the limb that may be used to augment computational models of sensory-motor control, and to inform clinical assessment of sensory function in patients with sensory-motor deficits

Perceived Object Stability Depends on Multisensory Estimates of Gravity

BACKGROUND: How does the brain estimate object stability? Objects fall over when the gravity-projected centre-of-mass lies outside the point or area of support. To estimate an object's stability visually, the brain must integrate information across the shape and compare its orientation to gravity. When observers lie on their sides, gravity is perceived as tilted toward body orientation, consistent with a representation of gravity derived from multisensory information. We exploited this to test whether vestibular and kinesthetic information affect this visual task or whether the brain estimates object stability solely from visual information. METHODOLOGY/PRINCIPAL FINDINGS: In three body orientations, participants viewed images of objects close to a table edge. We measured the critical angle at which each object appeared equally likely to fall over or right itself. Perceived gravity was measured using the subjective visual vertical. The results show that the perceived critical angle was significantly biased in the same direction as the subjective visual vertical (i.e., towards the multisensory estimate of gravity). CONCLUSIONS/SIGNIFICANCE: Our results rule out a general explanation that the brain depends solely on visual heuristics and assumptions about object stability. Instead, they suggest that multisensory estimates of gravity govern the perceived stability of objects, resulting in objects appearing more stable than they are when the head is tilted in the same direction in which they fall

Proteolysis of proBDNF Is a Key Regulator in the Formation of Memory

It is essential to understand the molecular processes underlying long-term memory to provide therapeutic targets of aberrant memory that produce pathological behaviour in humans. Under conditions of recall, fully-consolidated memories can undergo reconsolidation or extinction. These retrieval-mediated memory processes may rely on distinct molecular processes. The cellular mechanisms initiating the signature molecular events are not known. Using infusions of protein synthesis inhibitors, antisense oligonucleotide targeting brain-derived neurotrophic factor (BDNF) mRNA or tPA-STOP (an inhibitor of the proteolysis of BDNF protein) into the hippocampus of the awake rat, we show that acquisition and extinction of contextual fear memory depended on the increased and decreased proteolysis of proBDNF (precursor BDNF) in the hippocampus, respectively. Conditions of retrieval that are known to initiate the reconsolidation of contextual fear memory, a BDNF-independent memory process, were not correlated with altered proBDNF cleavage. Thus, the processing of BDNF was associated with the acquisition of new information and the updating of information about a salient stimulus. Furthermore, the differential requirement for the processing of proBDNF by tPA in distinct memory processes suggest that the molecular events actively engaged to support the storage and/or the successful retrieval of memory depends on the integration of ongoing experience with past learning

Protection by Anti-β-Glucan Antibodies Is Associated with Restricted β-1,3 Glucan Binding Specificity and Inhibition of Fungal Growth and Adherence

Anti-β-glucan antibodies elicited by a laminarin-conjugate vaccine confer cross-protection to mice challenged with major fungal pathogens such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans. To gain insights into protective β-glucan epitope(s) and protection mechanisms, we studied two anti-β-glucan monoclonal antibodies (mAb) with identical complementarity-determining regions but different isotypes (mAb 2G8, IgG2b and mAb 1E12, IgM). C. albicans, the most relevant fungal pathogen for humans, was used as a model

Theories in Business and Information Systems Engineering

Even though the idea of science enjoys an impressive reputation, there seems to be no precise conception of science. On the one hand, there is no unified definition of the extension of activities subsumed under the notion of science. According to the narrow conception that is common in Anglo-Saxon countries, science is restricted to those disciplines that investigate nature and aim at explanation and prediction of natural phenomena. A wider conception that can be found in various European countries includes social sciences, the humanities and engineering. On the other hand and related to the first aspect, there is still no general consensus on the specific characteristics of scientific discoveries and scientific knowledge

Update on the use of aromatase inhibitors in early-stage breast cancer

Aromatase inhibitors are currently included in the 'optimal' management of early-stage breast cancer. Uncertainty remains, however, as to the most appropriate treatment strategy, particularly for newly diagnosed women as they seek to trade off the cost, toxicities and efficacy of the treatment options. Recent publications provide conflicting advice on the role of aromatase inhibitors in the treatment of postmenopausal patients with early-stage hormone receptor-positive breast cancer. This review provides updates on the clinical trials of aromatase inhibitors in early breast cancer and tries to provide practical clinical guidance on their optimal use