HIV-1 and Alzheimer: a real conection?

La infección por el virus de inmunodeficiencia humana (VIH) causa alteraciones neurológicas que son más graves y frecuentes como consecuenia del envejecimieno de la población. Este daño se asocia a la disfunción neuronal, que patológicamente se caracteriza como una pérdida de sinapsis, acortamiento de neuritas, anormalidades dendríticas, así comon pérdida neuronal. A este respecto, varios estudios han observado un aumento significativo de placas amiloides en cerebros de individuos infectados por el VIH en comparación con controles sanos, así como en individuos VIH positivos que habían estado expuestos a la terapia antirretroviral. En este trabajo se ha investigado el efecto de la combinación del péptido β-amiloide e infección por VIH-1 en diferentes células del sistema nervioso. El pretratamiento de las células gliales y neuronales provoca un incremento en la replicación viral, así como el tratamiento combinado virus y formas de oligómeros y fibrillas producen un incremento en las especies reactivas de oxígeno y de la forma activa de la enzima proapoptótica caspasa-3, en astrocitos. Lo que podría traducirse como un incremento de neurotoxicidad y depositos de β-amiloide en el cerebro infectado.Infection by human immunodeficiency virus (HIV) promotes neurological alterations which are more severe and frequents, due to the aging of the population. This dementia is associated to neuronal disfunction, and is pathologicaly characterized as sinapse lose, dendritic abnormalities and neuronal death. Supporting this, several studies have shown a significant increase of the amyloid plaques in infected HIV brains compared to healthy controls as well as HIV positive individuals which were exposed to antiretroviral therapy. In the present study we have investigated the combined effect of amyloid-β and HIV-1 infection in diferent nervous cells. When we pretreated glial cells and neurons we found an increased viral replication, as well as the combined treatment of HIV and oligomeric and fibrils forms of amyloid-β which produce glial increased levels of oxygen reactive species and the proapoptotic enzyme caspase-3. These observations could be traduced in an increased neurotoxicity and amyloid-β deposits in infected brains

GCN2 has inhibitory effect on human immunodeficiency virus-1 protein synthesis and is cleaved upon viral infection

The reversible phosphorylation of the alpha-subunit of eukaryotic translation initiation factor 2 (eIF2alpha) is a well-characterized mechanism of translational control in response to a wide variety of cellular stresses, including viral infection. Beside PKR, the eIF2alpha kinase GCN2 participates in the cellular response against viral infection by RNA viruses with central nervous system tropism. PKR has also been involved in the antiviral response against HIV-1, although this antiviral effect is very limited due to the distinct mechanisms evolved by the virus to counteract PKR action. Here we report that infection of human cells with HIV-1 conveys the proteolytic cleavage of GCN2 and that purified HIV-1 and HIV-2 proteases produce direct proteolysis of GCN2 in vitro, abrogating the activation of GCN2 by HIV-1 RNA. Transfection of distinct cell lines with a plasmid encoding an HIV-1 cDNA clone competent for a single round of replication resulted in the activation of GCN2 and the subsequent eIF2alpha phosphorylation. Moreover, transfection of GCN2 knockout cells or cells with low levels of phosphorylated eIF2alpha with the same HIV-1 cDNA clone resulted in a marked increase of HIV-1 protein synthesis. Also, the over-expression of GCN2 in cells led to a diminished viral protein synthesis. These findings suggest that viral RNA produced during HIV-1 infection activates GCN2 leading to inhibition of viral RNA translation, and that HIV-1 protease cleaves GCN2 to overcome its antiviral effect

Generation of a novel three-dimensional scaffold-based model of the bovine endometrium

Bovine in vitro endometrial models that resemble tissue function in vivo are needed to study infertility, long-term uterine alterations induced by pathogens and impact of endocrine disruptor chemicals on reproductive function and other reproductive system complications that cause high economic losses in livestock species. The present study aimed to generate an innovative, reproducible, and functional 3D scaffold-based model of the bovine endometrium structurally robust for long term-culture. We developed a multicellular model containing both endometrial epithelial and stromal cells. Epithelial cells organized to form a luminal-like epithelial layer on the surface of the scaffold. Stromal cells produced their own extracellular matrix forming a stable subepithelial compartment that physiologically resembles the normal endometrium. Both cell types released prostaglandin E2 and prostaglandin F2α following a treatment with oxytocin and arachidonic acid. Additionally signal pathways mediating oxytocin and arachidonic acid stimulation of prostaglandin synthesis were analyzed by real time PCR (RT-PCR). Oxytocin receptor (OXTR), prostaglandin E2 receptor 2 (EP2), prostaglandin E2 receptor 4 (EP4), prostaglandin F receptor (PTGFR), prostaglandin E synthase (PTGES), PGF-synthase (PGFS) and prostaglandin-endoperoxide synthase 2 (COX-2) expression was detected in both control and treatment groups, however, only significant changes in abundance of OXTR mRNA transcripts were found. The results obtained by this study are a step forward in bovine in vitro culture technology. This 3D scaffold-based model provides a platform to study regulatory mechanisms involved in endometrial physiology and can set the basis for a broader tool for designing and testing novel therapeutic strategies for recurrent uterine pathologies

Thermogalvanic effects on the corrosion of copper in heavy brine LiBr solutions

Thermogalvanic corrosion of copper in heavy brine LiBr solutions has been investigated using a zero-resistance ammeter (ZRA). The temperature gradients between copper electrodes immersed in the same LiBr solution result in the formation of thermogalvanic cells with hot anodes, leading to high and sustained thermogalvanic currents. Copper loss rates, calculated using Faraday's law, substantially exceed 0.025 mm year−1, a value regarded as the threshold of low corrosion rates. The effects of thermogalvanic coupling on the surface properties of the anode and the cathode have been analysed by means of electrochemical impedance spectroscopy (EIS). The results obtained in this analysis have been related to the process of copper electrodissolution in bromide media

The Ground State of Graphene and Graphene Disordered by Vacancies

Graphene clusters consisting of 24 to 150 carbon atoms and hydrogen termination at the zigzag boundary edges have been studied, as well as clusters disordered by vacancy(s). Density Function Theory and Gaussian03 software were used to calculate graphene relative stability, desorption energy, band gap, density of states, surface shape, dipole momentum and electrical polarization of all clusters by applying the hybrid exchange-correlation functional Beke-Lee-Yang-Parr. Furthermore, infrared frequencies were calculated for two of them. Different basis sets, 6-31g**, 6-31g* and 6-31g, depending on the sizes of clusters are considered to compromise the effect of this selection on the calculated results. We found that relative stability and the gap decreases according to the size increase of the graphene cluster. Mulliken charge variation increase with the size. For about 500 carbon atoms, a zero HOMO-LUMO gap amount is predicted. Vacancy generally reduces the stability and having vacancy affects the stability differently according to the location of vacancies. Surface geometry of each cluster depends on the number of vacancies and their locations. The energy gap changes as with the location of vacancies in each cluster. The dipole momentum is dependent on the location of vacancies with respect to one another. The carbon-carbon length changes according to each covalence band distance from the boundary and vacancies. Two basis sets, 6-31g* and 6-31g**, predict equal amount for energy, gap and surface structure, but charge distribution results are completely different.Comment: 21 pages, 14 figures, 2 table

Leisure Attitude, Self-Rated Health, and Psychological Well-Being in Older Adults: A Moderated Mediation Model

Francisco Rodríguez-Cifuentes,1,* M Angeles López-Gonzalez,1,* Fernando Rubio-Garay,2,* Gabriela Topa,3,* Pedro Belo,4,* Ricardo Pocinho,5,* Silvia Silva,6,* Juan José Fernández-Muñoz1,* 1Psychology Department, Faculty of Health Sciences, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain; 2Associated Center in Albacete, Universidad Nacional de Educación a Distancia, Albacete, Spain; 3Department of Social and Organizational Psychology, Faculty of Psychology, Universidad Nacional de Educación a Distancia, Madrid, Spain; 4Instituto Politécnico de Setúbal, Setúbal, Portugal; 5Instituto Politécnico de Leira- CICS NOVA, Leira, Portugal; 6Escola Superior de Educação e Ciências Sociais Instituto Politécnico de Leiria, Leiria, Portugal*These authors contributed equally to this workCorrespondence: M Angeles López-Gonzalez, Psychology Department, Faculty of Health Sciences, Universidad Rey Juan Carlos, Av. de Atenas, s/n, Alcorcón, Madrid, 28922, Spain, Email [email protected]: A positive leisure attitude among older adults may have a beneficial effect on psychological well-being, both directly and indirectly by fostering a more positive perception of one’s health. This paper presents a correlational design that explores associations among leisure attitude, self-rated health, and psychological well-being, and analyzes the potential moderating role of gender in these relationships.Patients and Methods: The sample was selected using simple random probability sampling (N= 409; 61.9% female; Mean age = 72.9; SD = 8.43¸ Range of age 53 to 93 years). Diverse sociodemographic information was collected, and leisure attitudes, self-perceived health, and psychological well-being (positive affect and emotional ties) were assessed.Results: The results revealed a positive effect of leisure attitude on self-rated health and psychological well-being, with self-rated health fully mediating the association between the behavioral component of leisure attitude and psychological well-being. Furthermore, the moderating effect of gender on the relationship between self-rated health and psychological well-being was stronger among men.Conclusion: Positive cognitive and emotional perceptions of leisure among older adults seem to benefit psychological well-being and improve self-rated health, thereby contributing to healthy ageing.Keywords: ageing, older adults, gender, attitudes to leisure, psychological well-being, emotional tie

Updating known distribution models for forecasting climate change impact on endangered species

To plan endangered species conservation and to design adequate management programmes, it is necessary to predict their distributional response to climate change, especially under the current situation of rapid change. However, these predictions are customarily done by relating de novo the distribution of the species with climatic conditions with no regard of previously available knowledge about the factors affecting the species distribution. We propose to take advantage of known species distribution models, but proceeding to update them with the variables yielded by climatic models before projecting them to the future. To exemplify our proposal, the availability of suitable habitat across Spain for the endangered Bonelli’s Eagle (Aquila fasciata) was modelled by updating a pre-existing model based on current climate and topography to a combination of different general circulation models and Special Report on Emissions Scenarios. Our results suggested that the main threat for this endangered species would not be climate change, since all forecasting models show that its distribution will be maintained and increased in mainland Spain for all the XXI century. We remark on the importance of linking conservation biology with distribution modelling by updating existing models, frequently available for endangered species, considering all the known factors conditioning the species’ distribution, instead of building new models that are based on climate change variables only.Ministerio de Ciencia e Innovación and FEDER (project CGL2009-11316/BOS

Effects of highly active antiretroviral therapy with nelfinavir in vertically HIV-1 infected children: 3 years of follow-up. Long-term response to nelfinavir in children

BACKGROUND: Antiretroviral treatment (ART) in children has special features and consequently, results obtained from clinical trials with antiretroviral drugs in adults may not be representative of children. Nelfinavir (NFV) is an HIV-1 Protease Inhibitor (PI) which has become as one of the first choices of PI for ART in children. We studied during a 3-year follow-up period the effects of highly active antiretroviral therapy with nelfinavir in vertically HIV-1 infected children. METHODS: Forty-two vertically HIV-infected children on HAART with NFV were involved in a multicentre prospective study. The children were monitored at least every 3 months with physical examinations, and blood sample collection to measure viral load (VL) and CD4+ cell count. We performed a logistic regression analysis to determinate the odds ratio of baseline characteristics on therapeutic failure. RESULTS: Very important increase in CD4+ was observed and VL decreased quickly and it remained low during the follow-up study. Children with CD4+ <25% at baseline achieved CD4+ >25% at 9 months of follow-up. HIV-infected children who achieved undetectable viral load (uVL) were less than 40% in each visit during follow-up. Nevertheless, HIV-infected children with VL >5000 copies/ml were less than 50% during the follow-up study. Only baseline VL was an important factor to predict VL control during follow-up. Virological failure at defined end-point was confirmed in 30/42 patients. Along the whole of follow-up, 16/42 children stopped HAART with NFV. Baseline characteristics were not associated with therapeutic change. CONCLUSION: NFV is a safe drug with a good profile and able to achieve an adequate response in children

Prevalence of SARS-CoV-2 Infection at the University of Barcelona during the Third COVID-19 Pandemic Wave in Spain

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic started in December 2019 and still is a major global health challenge. Lockdown measures and social distancing sparked a global shift towards online learning, which deeply impacted universities' daily life, and the University of Barcelona (UB) was not an exception. Accordingly, we aimed to determine the impact of the SARS-CoV-2 pandemic at the UB. To that end, we performed a cross-sectional study on a sample of 2784 UB members (n = 52,529). Participants answered a brief, ad hoc, online epidemiological questionnaire and provided a nasal swab for reverse transcription polymerase chain reaction (RT-PCR) SARS-CoV-2 analysis and a venous blood sample for SARS-CoV-2 IgG antibody assay. Total prevalence of SARS-CoV-2 infection (positive RT-PCR or positive IgG) was 14.9% (95%CI 13.3 to 17.0%). Forty-four participants (1.6%, 95%CI: 1.2-2.1%) were positive for SARS-CoV-2 RT-PCR. IgG against SARS-CoV-2 was observed in 12.8% (95%CI: 11.6-14.1%) of participants. Overall, while waiting for population vaccination and/or increased herd immunity, we should concentrate on identifying and isolating new cases and their contact

Shogaol-huprine hybrids: Dual antioxidant and anticholinesterase agents with beta-amyloid and tau anti-aggregating properties

Multitarget compounds are increasingly being pursued for the effective treatment of complex diseases. Herein, we describe the design and synthesis of a novel class of shogaolhuprine hybrids, purported to hit several key targets involved in Alzheimer"s disease. The hybrids have been tested in vitro for their inhibitory activity against human acetylcholinesterase and butyrylcholinesterase and antioxidant activity (ABTS.+, DPPH and Folin-Ciocalteu assays), and in intact Escherichia coli cells for their Aβ42 and tau anti-aggregating activity. Also, their brain penetration has been assessed (PAMPA-BBB assay). Even though the hybrids are not as potent AChE inhibitors or antioxidant agents as the parent huprine Y and [4]-shogaol, respectively, they still exhibit very potent anticholinesterase and antioxidant activities and are much more potent Aβ42 and tau anti-aggregating agents than the parent compounds. Overall, the shogaolhuprine hybrids emerge as interesting brain permeable multitarget anti-Alzheimer leads