A biomarker for tegumentary and visceral leishmaniasis based on a recombinant Leishmania hypothetical protein

The measures for leishmaniasis control include the precise diagnosis of disease. However, although several recombinant antigens have been tested with this biotechnological purpose, no effective product exists, which could detects patients with the active disease, as well as differentiates them from cured and treated patients. In this study, a conserved Leishmania hypothetical protein, which was identified in Leishmania infantum parasites, but evaluated to presents high homology in the amino acid sequences between distinct parasite species, was evaluated for the diagnosis of tegumentary and visceral leishmaniasis. In addition, PBMCs collected from treated and untreated mucosal leishmaniasis (ML) and visceral leishmaniasis (VL) patients, as well as in healthy subjects living in endemic region of disease, were in vitro stimulated, when IFN-γ, IL-4 and IL-10 levels were evaluated in the cell supernatant. Regarding the serological analyses, ELISA experiments using the recombinant protein (rLiHyL) and a human serological panel revealed high sensitivity and specificity values to detect both diseases, while control antigens showed worst results. Regarding the cellular response, results showed that rLiHyL-stimulated cells produced higher IFN-γ and lower IL-4 and IL-10 levels in the supernatants. Also, the anti-protein antibody production was evaluated in these patients, and data showed higher IgG2 and lower IgG1 levels found in the treated patients and healthy controls, demonstrating the stimulation of a Th1-type response induced by the rLiHyL protein. In conclusion, this hypothetical protein can be considered as antigenic in TL and VL, as well as a vaccine candidate to be tested in future studies to protect against disease.     

An Optogenetic Study of the Electrophysiological Properties of Hippocampal Neurons in PS1-M146V Transgenic Mice (a model of Alzheimer’s disease)

Neuroscience and Behavioral Physiology - We report here a comparative (using chemical, electrical, and optical stimulation) study of the electrophysiological properties of cultured hippocampal...     

Mapping and definition of HLA class I and II serologic epitopes using an unbiased reverse engineering strategy

Current models describing HLA epitopes are both theoretical and empirical. Each has limitations yielding discordant results and increasingly complex modeling. The models make a priori assumptions that epitopes must be present only on the mature protein, solvent accessible, on the ‘top’ (peptide binding surface) of the molecule, restricted to the same class as the antibody, and in the same position on the target allele if reactive to more than one locus. Results obtained counter to these assumptions are routinely discounted. For the 17th International Histocompatibility and Immunogenetics Workshop, we developed a reverse engineering algorithm to define epitopes without these assumptions on a cohort of 332 primary transplant pairs. Complete NGS typing of the transcribed (including leader) genomic DNA for 11 HLA loci of donor and recipient and DSA assignment by single antigen beads was performed. Our results show that, when grouped by 16 class I and II allele specific DSA, uniform clusters and 172 specific amino acid target epitopes are recognized by recipients despite originating from disparate HLA pairs. Data also show that these targets can be in the leader, alpha 3, transmembrane and cytoplasmic domains, thus calling into question current assumptions regarding immunogenic epitopes. Comparisons of amino acid epitopes defined by the Terasaki and Duquesnoy groups (TerEp and EpRegistry) are given.     

Association of Chronotype,Road Traffic Accidents,and Polymorphisms in Genes Linked with the Biological Clock and the Dopaminergic System

Neuroscience and Behavioral Physiology - Objective. To study the association between single-nucleotide polymorphisms (SNP) of the RORA (rs1159814), CLOCK (rs12649507), PER3 (rs2640909), NPSR1...     

The Role of Stretch-Activated Channels in Mediating mTORC1 Signaling in Isolated Rat Soleus Muscle in Response to Mechanical Stimulation after Functional Unloading

Neuroscience and Behavioral Physiology - The aim of the present work was to identify the role of stretch-activated ion channels (SAC) in the transmission of mechanical signals to the key...     

Assessment of objective dynamic knee joint control in anterior cruciate ligament deficient and reconstructed individuals

BackgroundThere is a lack of objective dynamic knee joint control measures that can be related to the status of the anterior cruciate ligament (ACL). The purpose of this study was to introduce two novel measures and apply a third to determine how dynamic knee joint control changes in relation to ACL status during dynamic movements.MethodsTwenty patients (13 male) were tested pre- (ACLd) and 10-months post- (ACLr) ACL reconstructive surgery and matched to an uninjured participant (CON). Kinetic and kinematic data were synchronously recorded with a force platform and motion capture system. Three objective control measures including dynamic angular stiffness, knee joint center excursion (KJCE), and knee joint center boundary (KJCB) were assessed for each participant when completing the side cut and hop tasks.ResultsDuring the side cut, stiffness was found to be significantly lower in ACLd (0.06 ± 0.01 Nm/kg/°) and ACLr (0.07 ± 0.02 Nm/kg/°) compared to CON (0.08 ± 0.02 Nm/kg/°), while there were no differences in stiffness during the hop. No significant differences were observed in the KJCE during the side cut, while KJCE was significantly greater (p = 0.006) during the hop in CON compared to the ACLd. There were no differences in KJCB.ConclusionsThese high-functioning ACL injured in both ACLd and ACLr phases, aside from reduced stiffness, were able to complete both tasks with similar dynamic control as the CON. Although improvements in self-perceived control between ACLd and ACLr have been observed, this lack of improvement in objective control demonstrates a gap between a patient's self-efficacy and the level of control.     

Detection of “Candidatus Rickettsia wissemanii” in ticks parasitizing bats (Mammalia: Chiroptera) in the northern Brazilian Amazon

A total of 482 bats representing 32 species and two families were captured in the Amazon forests of the Amapá state in northern Brazil. Nineteen Artibeus planirostris bats (3.9 %) were infested with 160 ticks, all identified as Ornithodoros hasei. Three pools of larvae were screened for rickettsial DNA via polymerase chain reaction (PCR) targeting three rickettsial genes: gltA, ompA and htrA. Only one of them yielded an amplicons of the expected size for all three molecular assays. Comparisons of the obtained sequences including a phylogenetic analysis confirmed the occurrence of “Candidatus Rickettsia wissemanii” in Brazil.

     

The effects of parenteral nutrition on food intake and gastric motility

Frequently, patients receiving parenteral nutrition (PN) report hunger during the parenteral infusion, yet experience early satiety once PN is tapered off. Post-PN satiety can interfere with the ability to consume enough nutrients to maintain body weight and nutritional status. Factors such as caloric quantity of infusate, gastric motility changes, and disease pathology have been related to appetite changes. To investigate the effects of PN on food intake and gastric motility without the complicated interactions associated with disease pathology, four normal, healthy rhesus monkeys (Macaca mulatta) were studied. The monkeys were administered PN in amounts ranging from 25% to 100% of their normal daily caloric intake. Food and water were continuously available. PN consistently suppressed voluntary food intake in direct relationship to the amount of nutrient infused. The frequency of large-amplitude hunger-type gastric contractions decreased from control conditions. Upon cessation of PN, appetite remained suppressed for one to two weeks, indicating a self-limiting physiological basis to post-PN satiety. Thus, reduced appetite following PN termination might occur in the clinical setting and the patients' feelings of satiety may not be completely attributed to lack of cooperation or disease pathology.