Sensory Activation of Command Cells for Locomotion and Modulatory Mechanisms: Lessons from Lampreys

Sensorimotor transformation is one of the most fundamental and ubiquitous functions of the central nervous system. Although the general organization of the locomotor neural circuitry is relatively well understood, less is known about its activation by sensory inputs and its modulation. Utilizing the lamprey model, a detailed understanding of sensorimotor integration in vertebrates is emerging. In this article, we explore how the vertebrate central nervous system integrates sensory signals to generate motor behavior by examining the pathways and neural mechanisms involved in the transformation of cutaneous and olfactory inputs into motor output in the lamprey. We then review how 5-HT acts on these systems by modulating both sensory inputs and motor output. A comprehensive review of this fundamental topic should provide a useful framework in the fields of motor control, sensorimotor integration and neuromodulation

In Vivo Anti-Diabetic Activity of the Ethanolic Crude Extract of Sorbus decora C.K.Schneid. (Rosacea): A Medicinal Plant Used by Canadian James Bay Cree Nations to Treat Symptoms Related to Diabetes

A number of potential anti-diabetic plants were identified through an ethnobotanical survey of the traditional pharmacopeia of the Cree of Eeyou Istchee (CEI—Northeastern Canada) used against symptoms of diabetes and their biological activity assessed by in vitro bioassays. Among these, Sorbus decora C.K.Schneid. (Rosacea) ranked highly and increased the transport of glucose in skeletal muscle cells in culture. The present study thus aimed at confirming the antidiabetic potential of S. decora in in vivo models of insulin resistance and diabetes, notably the streptozotocin Type 1 diabetic rat (STZ), the genetic KK-Ay Type 2 diabetic mouse and the rat rendered insulin resistant with 10% glucose water consumption for 6 weeks. Sorbus decora ethanolic crude extract (SDEE) was administered orally (200 mg kg−1) and compared to metformin (150 or 500 mg kg−1). The intragastric (i.g.) gavage of SDEE transiently decreased glycemia in STZ rats in a bi-phasic manner but the effect was cumulative over several days. In KK-Ay mice, SDEE incorporated in food (0.12%) decreased glycemia by 15% within 1 week as compared to vehicle controls. In pre-diabetic insulin-resistant rats, SDEE fed daily by i.g. gavage for 2 weeks significantly decreased the slight hyperglycemia and hyperinsulinemia, without affecting sugar water intake. Using the HOMA insulin resistance parameter, the effect of SDEE was equivalent to that of metformin. In conclusion, the ethanolic crude extract of S. decora demonstrates both anti-hyperglycemic and insulin-sensitizing activity in vivo, thereby confirming anti-diabetic potential and validating CEI traditional medicine

Sobre a Faixa de Pedestres

The interference colors resulting from thin films of Al 2O 3 deposited by atomic layer deposition (ALD) on silicon have been rigorously analyzed using a recently developed robotic gonioreflectometer. A series of eleven increasingly thick films was deposited, up to 1613 Å, and their reflectance values obtained for the visible spectrum. A comparison of these values with the predictions of computer simulations employing Fresnel equations has revealed that while there was generally good agreement between predicted and measured spectra, there are some spectral regions that exhibit large deviations from predicted reflectances, typically at near-normal measurement angles and shorter wavelengths. The effect of these discrepancies on color appearance was investigated in the CIE L*a*b* color space for the daylight illuminant D65. Large iridescence is both predicted and measured for most film thicknesses. Chroma and hue differences as large as 20 CIELAB units between the predicted and the measured color centers were obtained. Simulation also predicts larger iridescence than what is actually measured. A likely cause for the observed discrepancies is that the dielectric constants of the ALD films deviate from the literature values for the bulk material

Factors associated with sexual quality of life among men living with HIV

Introduction This study aims to assess the prevalence of sexual difficulties and identify factors associated with the Sexual Quality of Life (SQoL) among people living with HIV (PLWHA). Methods The study included 107 heterosexual men and 474 men who have sex with men (MSM) from five countries. Participants self-reported variables related to physical and mental health, as well as HIV-related parameters. Erectile or ejaculation difficulty, as well as low sexual desire, were investigated. SQoL was measured using the PROQOL-SexLife questionnaire. Results Most of participants reported low sexual desire, predominantly among MSM. Among MSM, living with a partner and healthcare satisfaction were associated with SQoL scores in POP dimension, while consistent condom use, cardiovascular complications, and being single were associated with SQoL scores in STI dimension. Viagra use, anti-cholesterol treatment, and living with a partner were associated with SQoL scores in DIS dimension. Among heterosexual men, employment and African origin were associated with SQoL scores in the POP dimension. Alcohol consumption was associated with SQoL scores in STI dimension. Conclusion This study underscores the importance of non-clinical determinants when assessing SQoL among PLWHA, emphasizing psychological factors and the perceived quality of healthcare. Tailored interventions should incorporate these findings to enhance overall SQoL outcomes

CD40-Activated B Cells Can Efficiently Prime Antigen-Specific Naïve CD8+ T Cells to Generate Effector but Not Memory T cells

Background: The identification of the signals that should be provided by antigen-presenting cells (APCs) to induce a CD8 + T cell response in vivo is essential to improve vaccination strategies using antigen-loaded APCs. Although dendritic cells have been extensively studied, the ability of other APC types, such as B cells, to induce a CD8 + T cell response have not been thoroughly evaluated. Methodology/Principal Findings: In this manuscript, we have characterized the ability of CD40-activated B cells, stimulated or not with Toll-like receptor (TLR) agonists (CpG or lipopolysaccharide) to induce the response of mouse naïve CD8 + T cells in vivo. Our results show that CD40-activated B cells can directly present antigen to naïve CD8 + T cells to induce the generation of potent effectors able to secrete cytokines, kill target cells and control a Listeria monocytogenes infection. However, CD40-activated B cell immunization did not lead to the proper formation of CD8 + memory T cells and further maturation of CD40-activated B cells with TLR agonists did not promote the development of CD8 + memory T cells. Our results also suggest that inefficient generation of CD8 + memory T cells with CD40-activated B cell immunization is a consequence of reduced Bcl-6 expression by effectors and enhanced contraction of the CD8 + T cell response. Conclusions: Understanding why CD40-activated B cell immunization is defective for the generation of memory T cells and gaining new insights about signals that should be provided by APCs are key steps before translating the use of CD40-B cel

Implementing telehealth to support medical practice in rural/remote regions: what are the conditions for success?

BACKGROUND: Telehealth, as other information and communication technologies (ICTs) introduced to support the delivery of health care services, is considered as a means to answer many of the imperatives currently challenging health care systems. In Canada, many telehealth projects are taking place, mostly targeting rural, remote or isolated populations. So far, various telehealth applications have been implemented and have shown promising outcomes. However, telehealth utilisation remains limited in many settings, despite increased availability of technology and telecommunication infrastructure. METHODS: A qualitative field study was conducted in four remote regions of Quebec (Canada) to explore perceptions of physicians and managers regarding the impact of telehealth on clinical practice and the organisation of health care services, as well as the conditions for improving telehealth implementation. A total of 54 respondents were interviewed either individually or in small groups. Content analysis of interviews was performed and identified several effects of telehealth on remote medical practice as well as key conditions to ensure the success of telehealth implementation. RESULTS: According to physicians and managers, telehealth benefits include better access to specialised services in remote regions, improved continuity of care, and increased availability of information. Telehealth also improves physicians' practice by facilitating continuing medical education, contacts with peers, and access to a second opinion. At the hospital and health region levels, telehealth has the potential to support the development of regional reference centres, favour retention of local expertise, and save costs. Conditions for successful implementation of telehealth networks include the participation of clinicians in decision-making, the availability of dedicated human and material resources, and a planned diffusion strategy. Interviews with physicians and managers also highlighted the importance of considering telehealth within the broader organisation of health care services in remote and rural regions. CONCLUSION: This study identified core elements that should be considered when implementing telehealth applications with the purpose of supporting medical practice in rural and remote regions. Decision-makers need to be aware of the specific conditions that could influence telehealth integration into clinical practices and health care organisations. Thus, strategies addressing the identified conditions for telehealth success would facilitate the optimal implementation of this technology

Kinin B1 Receptor Enhances the Oxidative Stress in a Rat Model of Insulin Resistance: Outcome in Hypertension, Allodynia and Metabolic Complications

BACKGROUND: Kinin B(1) receptor (B(1)R) is induced by the oxidative stress in models of diabetes mellitus. This study aims at determining whether B(1)R activation could perpetuate the oxidative stress which leads to diabetic complications. METHODS AND FINDINGS: Young Sprague-Dawley rats were fed with 10% D-Glucose or tap water (controls) for 8-12 weeks. A selective B(1)R antagonist (SSR240612) was administered acutely (3-30 mg/kg) or daily for a period of 7 days (10 mg/kg) and the impact was measured on systolic blood pressure, allodynia, protein and/or mRNA B(1)R expression, aortic superoxide anion (O(2)(*-)) production and expression of superoxide dismutase (MnSOD) and catalase. SSR240612 reduced dose-dependently (3-30 mg/kg) high blood pressure in 12-week glucose-fed rats, but had no effect in controls. Eight-week glucose-fed rats exhibited insulin resistance (HOMA index), hypertension, tactile and cold allodynia and significant increases of plasma levels of glucose and insulin. This was associated with higher aortic levels of O(2)(*-), NADPH oxidase activity, MnSOD and catalase expression. All these abnormalities including B(1)R overexpression (spinal cord, aorta, liver and gastrocnemius muscle) were normalized by the prolonged treatment with SSR240612. The production of O(2)(*-) in the aorta of glucose-fed rats was also measured in the presence and absence of inhibitors (10-100 microM) of NADPH oxidase (apocynin), xanthine oxidase (allopurinol) or nitric oxide synthase (L-NAME) with and without Sar[D-Phe(8)]des-Arg(9)-BK (20 microM; B(1)R agonist). Data show that the greater aortic O(2)(*-) production induced by the B(1)R agonist was blocked only by apocynin. CONCLUSIONS: Activation of kinin B(1)R increased O(2)(*-) through the activation of NADPH oxidase in the vasculature. Prolonged blockade of B(1)R restored cardiovascular, sensory and metabolic abnormalities by reducing oxidative stress and B(1)R gene expression in this model

A Novel Neural Substrate for the Transformation of Olfactory Inputs into Motor Output

Anatomical and physiological experiments in the lamprey reveal the neural circuit involved in transforming olfactory inputs into motor outputs, which was previously unknown in a vertebrate

Efficient Production of HIV-1 Virus-Like Particles from a Mammalian Expression Vector Requires the N-Terminal Capsid Domain

It is now well accepted that the structural protein Pr55Gag is sufficient by itself to produce HIV-1 virus-like particles (VLPs). This polyprotein precursor contains different domains including matrix, capsid, SP1, nucleocapsid, SP2 and p6. In the present study, we wanted to determine by mutagenesis which region(s) is essential to the production of VLPs when Pr55Gag is inserted in a mammalian expression vector, which allows studying the protein of interest in the absence of other viral proteins. To do so, we first studied a minimal Pr55Gag sequence called Gag min that was used previously. We found that Gag min fails to produce VLPs when expressed in an expression vector instead of within a molecular clone. This failure occurs early in the cell at the assembly of viral proteins. We then generated a series of deletion and substitution mutants, and examined their ability to produce VLPs by combining biochemical and microscopic approaches. We demonstrate that the matrix region is not necessary, but that the efficiency of VLP production depends strongly on the presence of its basic region. Moreover, the presence of the N-terminal domain of capsid is required for VLP production when Gag is expressed alone. These findings, combined with previous observations indicating that HIV-1 Pr55Gag-derived VLPs act as potent stimulators of innate and acquired immunity, make the use of this strategy worth considering for vaccine development