Fine-mapping the immunodominant antibody epitopes on consensus sequence-based HIV-1 envelope trimer vaccine candidates.

The HIV-1 envelope glycoprotein (Env) trimer is the key target for vaccines aimed at inducing neutralizing antibodies (NAbs) against HIV-1. The clinical candidate immunogen ConM SOSIP.v7 is a stabilized native-like HIV-1 Env trimer based on an artificial consensus sequence of all HIV-1 isolates in group M. In preclinical studies ConM SOSIP.v7 trimers induced strong autologous NAb responses in non-human primates (NHPs). To fine-map these responses, we isolated monoclonal antibodies (mAbs) from six cynomolgus macaques that were immunized three times with ConM SOSIP.v7 protein and boosted twice with the closely related ConSOSL.UFO.664 immunogen. A total of 40 ConM and/or ConS-specific mAbs were isolated, of which 18 were retrieved after the three ConM SOSIP.v7 immunizations and 22 after the two immunizations with ConSOSL.UFO.664. 22 mAbs (55%) neutralized the ConM and/or ConS virus. Cross-neutralization of ConS virus by approximately one-third of the mAbs was seen prior to ConSOSL.UFO.664 immunization, albeit with modest potency. Neutralizing antibodies predominantly targeted the V1 and V2 regions of the immunogens, with an apparent extension towards the V3 region. Thus, the V1V2V3 region is immunodominant in the potent NAb response elicited by two consensus sequence native-like HIV-1 Env immunogens. Immunization with these soluble consensus Env proteins also elicited non-neutralizing mAbs targeting the trimer base. These results inform the use and improvement of consensus-based trimer immunogens in combinatorial vaccine strategies.

Alcohol Consumption And Intensification Of Paranoid Traits In Attempted Homicide

@#There is strong evidence that paranoia can be an existing trait in the general population as a continuous dimension ranging from minimal levels to paranoid personality traits, and that at its maximum expression could take the form of disabling psychotic disorders such as delusional disorder or schizophrenia however, and according to Caviedes, GEC and Yonfá, EDA. Here are studies in which the existence of comorbidity between paranoid, borderline, antisocial and histrionic personality and problematic alcohol consumption is mentioned which in psychopathological terminology is called dual pathology (comorbidity of mental disorder and toxic consumption).

Cocaine Cravings, Borderline Personality Disorder & Attempted Homicide

@#In the 80’s, in Spain, there was a very significant increase in the population addicted to heroin use. The behaviour patterns of use and abuse of this substance also caused many drug addicts to be linked to the associated consumption of multiple toxic substances, favouring the appearance of politoxicomania. The origin of the change of model in drug use began in mid- 1987 and in the following years, ecstasy and the so-called designer drugs began to spread throughout the festival scene in the United Kingdom, Western Europe and the Iberian Peninsul. In the 90’s, new substances were introduced into society that had little to do with heroin use, shifting the link to toxic substances to these better accepted and less questioned substances, avoiding the possible problems associated with consumption in marginal environments. The normalization of the consumption of substances of abuse began to have a greater social tolerance, breaking the stigma that led to the alarm raised by heroin consumption in the 80’s. In this sense, drugs were no longer associated with marginalization, and were seen in environments considered festive and, therefore, “normal”. ASEAN Journal of Psychiatry, Vol. 22(5): July 2021: 1-4.

Optimisation of oat milk formulation to obtain fermented derivatives by using probiotic Lactobacillus reuteri microorganisms.

Functional advantages of probiotics combined with interesting composition of oat were considered as an alternative to dairy products. In this study, fermentation of oat milk with Lactobacillus reuteri and Streptococcus thermophilus was analysed to develop a new probiotic product. Central composite design with response surface methodology was used to analyse the effect of different factors (glucose, fructose, inulin and starters) on the probiotic population in the product. Optimised formulation was characterised throughout storage time at 4 ℃ in terms of pH, acidity, ß-glucan and oligosaccharides contents, colour and rheological behaviour. All formulations studied were adequate to produce fermented foods and minimum dose of each factor was considered as optimum. The selected formulation allowed starters survival above 10(7)/cfu ml to be considered as a functional food and was maintained during the 28 days controlled. ß-glucans remained in the final product with a positive effect on viscosity. Therefore, a new probiotic non-dairy milk was successfully developed in which high probiotic survivals were assured throughout the typical yoghurt-like shelf life.

Effect of hypolipidemic drugs on cholinesterase activity in the rat.

1. The effect of four hypolipidemic agents with different mechanisms of action (fenofibrate, probucol, colestipol and nicotinic acid) on plasma and liver cholinesterase has been studied. 2. Liver weight and liver weight/body weight ratio increased only after treatment with fenofibrate. 3. Plasma and liver cholinesterase activity increased markedly after fenofibrate, a strong peroxisome proliferator, and slightly after nicotinic acid, a weak peroxisome proliferator. 4. The data obtained suggest that increased cholinesterase activity is due to increased rate of fatty acid oxidation caused by peroxisome proliferators.