Assessing T-Cell Immunity in Kidney Transplant Recipients with Absent Antibody Production after a 3rd Dose of the mRNA-1273 Vaccine

The vulnerable population of kidney transplant recipients (KTRs) are low responders to COVID-19 vaccines, so specific immune surveillance is needed. The interferon-gamma (IFN-γ) release assay (IGRA) is effective in assessing T cell-mediated immunity. We assessed SARS-CoV-2-directed T cell responses in KTRs with absent antibody production after a third dose of the mRNA-1273 vaccine, using two different IGRAs. A cohort of 57 KTRs, who were actively followed up, received a third dose of the mRNA-1273 vaccine. After the evaluation of humoral immunity to SARS-CoV-2, 14 seronegative patients were tested with two commercial IGRAs (SD Biosensor and Euroimmun). Out of 14 patients, one and three samples were positive by IGRAs with Euroimmun and SD Biosensor, respectively. The overall agreement between the two assays was 85.7% (κ = 0.444). In addition, multivariate linear regression analysis showed no statistically significant association between the IFN-γ concentration, and the independent variables analyzed (age, gender, years since transplant, total lymphocytes cells/mcl, CD3+ cells/mcl, CD3+ CD4+ cells/mcl, CD3+ CD8+ cells/mcl, CD19+ cells/mcl, CD3-CD16+CD56+ cells/mcl) (p > 0.01). In a vulnerable setting, assessing cellular immune response to complement the humoral response may be advantageous. Since the two commercial IGRAs showed a good agreement on negative samples, the three discordant samples highlight the need for further investigations.     

Application of chemometric tools in the development of food bars based on cocoa shell,soy flour and green banana flour

In this study, exploratory methods and the simplex-centroid design were applied in the development of food bars with cocoa shell, soy and green banana flours that were evaluated sensorially. The results of the chemical composition and texture were submitted to the Scott-Knott test and the Principal Component Analysis, and was observed a significant difference between the treatments (P < 0.05), as well as a tendency to form five groups, according to its nutritional characteristics. The design used to optimise the sensorial acceptance of the food bars was effective, whose contour surface indicated an optimal region with greater acceptance, with all formulations having good acceptance (scores above 5.52). Check-All-That-Apply, Contingency Analysis and Hierarchical Cluster Analysis allowed describing the products, demonstrating the sensory differences between treatments with the presence/absence of cocoa shell. It is concluded that the studied ingredients can be used in food bars, providing nutritional and sensory characteristics acceptable to the consumer.     

Automated robotic platforms in design and development of formulations

Product design for formulations is an active and challenging area of research. The new challenges of a fast-paced market, products of increasing complexity, and practical translation of sustainability paradigms require to re-examine the existing theoretical frameworks to include the advantages deriving from the new reality of digitalization of business and research. In this work, we review the existing approaches, clearly stating the role of automation and machine-learning-guided optimization in the broader framework. Moving from this, we review the state of the art of automated hardware and software for formulated product design, and identify the open challenges for future research. Perspectives are given on the emerging fields of automated discovery, scale-up, and multistage optimization, and a unitary picture of the existing connections is provided, in the general context of a completely digital R&D workflow.     

High Glucose and Liver Fatty Acid Binding Protein Gene Ablation Differentially Impact Whole Body and Liver Phenotype in High-Fat Pair-Fed Mice

Ad libitum-fed diets high in fat and carbohydrate (especially fructose) induce weight gain, obesity, and nonalcoholic fatty liver disease (NAFLD) in humans and animal models. However, interpretation is complicated since ad libitum feeding of such diets induces hyperphagia and upregulates expression of liver fatty acid binding protein (L-FABP)—a protein intimately involved in fatty acid and glucose regulation of lipid metabolism. Wild-type (WT) and L-fabp gene ablated (LKO) mice were pair-fed either high-fat diet (HFD) or high-fat/high-glucose diet (HFGD) wherein total carbohydrate was maintained constant but the proportion of glucose was increased at the expense of fructose. In LKO mice, the pair-fed HFD increased body weight and lean tissue mass (LTM) but had no effect on fat tissue mass (FTM) or hepatic fatty vacuolation as compared to pair-fed WT counterparts. These LKO mice exhibited upregulation of hepatic proteins in fatty acid uptake and cytosolic transport (caveolin and sterol carrier protein-2), but lower hepatic fatty acid oxidation (decreased serum β-hydroxybutyrate). LKO mice pair-fed HFGD also exhibited increased body weight; however, these mice had increased FTM, not LTM, and increased hepatic fatty vacuolation as compared to pair-fed WT counterparts. These LKO mice also exhibited upregulation of hepatic proteins in fatty acid uptake and cytosolic transport (caveolin and acyl-CoA binding protein, but not sterol carrier protein-2), but there was no change in hepatic fatty acid oxidation (serum β-hydroxybutyrate) as compared to pair-fed WT counterparts.     

Quantitative Proteomics Reveals Changes Induced by TIMP-3 on Cell Membrane Composition and Novel Metalloprotease Substrates

Ectodomain shedding is a key mechanism of several biological processes, including cell-communication. Disintegrin and metalloproteinases (ADAMs), together with the membrane-type matrix metalloproteinases, play a pivotal role in shedding transmembrane proteins. Aberrant shedding is associated to several pathological conditions, including arthritis. Tissue inhibitor of metalloproteases 3 (TIMP-3), an endogenous inhibitor of ADAMs and matrix metalloproteases (MMPs), has been proven to be beneficial in such diseases. Thus, strategies to increase TIMP-3 bioavailability in the tissue have been sought for development of therapeutics. Nevertheless, high levels of TIMP-3 may lead to mechanism-based side-effects, as its overall effects on cell behavior are still unknown. In this study, we used a high-resolution mass-spectrometry-based workflow to analyze alterations induced by sustained expression of TIMP-3 in the cell surfaceome. In agreement with its multifunctional properties, TIMP-3 induced changes on the protein composition of the cell surface. We found that TIMP-3 had differential effects on metalloproteinase substrates, with several that accumulated in TIMP-3-overexpressing cells. In addition, our study identified potentially novel ADAM substrates, including ADAM15, whose levels at the cell surface are regulated by the inhibitor. In conclusion, our study reveals that high levels of TIMP-3 induce modifications in the cell surfaceome and identifies molecular pathways that can be deregulated via TIMP-3-based therapies.     

A Data-Reusing Nonlinear Gradient Descent Algorithm for a Class of Complex-Valued Neural Adaptive Filters

A complex-valued data-reusing nonlinear gradient descent (CDRNGD) learning algorithm for a class of complex-valued nonlinear neural adaptive filters is introduced and the affinity between the family of data-reusing algorithms and the class of normalised gradient descent algorithms is examined. Error bounds on the class of complex data-reusing algorithms are established and indicate the stability of such algorithms. Experiments on nonlinear inputs show the class of complex data-reusing algorithms outperforming the standard complex nonlinear gradient descent algorithms and converging to the normalised complex non-linear gradient descent algorithm without experiencing the stability problems commonly encountered with normalised gradient descent algorithms. This revised version was published online in June 2006 with corrections to the Cover Date.     

Chemical constituents of some basidiomycetes

The sterol, fatty acid and free amino acid (FAA) contents of some Basidiomycetes were determined. The overall sterol distribution was similar to that of other mushrooms, with ergosterol as the predominant sterol accompanied by the other closely related sterols. The mushrooms examined also contained high levels of fatty acids of which linoleic is the most prominent. Glutamic acid, valine and proline were the dominant FAA.     

Different patterns of biting attack employed by lactating female mice (Mus domesticus) in encounters with male and female conspecific intruders.

Attacks by resident lactating female mice were examined in a variety of situations. Relatively few attack bites to vulnerable body regions were seen when pairs of unfamiliar lactating females fought, establishing social status prior to communal nesting. Sexually naive male and female intruders were equally prone to attack by lactating females, but patterns of bite attack generated by them were very different; males received the more damaging attacks. More signs of "fear" were seen in the lactating females' responses to male rather than female intruders. Varied motivations may underlie attacks by lactating females directed to conspecific intruders. Defensive patterns of biting by lactating females are more consistently directed towards males, intruders that are more likely to harm or destroy the litter. Although attacks by females rarely thwarted infanticide by male intruders, the behavior may acutely protect parental investment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

CPITN: time and cost estimates for periodontal prevention and treatment procedures

PBMC from individuals both exposed and non-exposed to leishmaniae proliferative and produce interferon-gamma (IFN-gamma) following stimulation with Leishmania antigens. We studied the kinetics of the proliferative response of PBMC from non-exposed individuals and from patients recovering from visceral leishmaniasis due to Leishmania infantum, using heat-killed stationary-phase promastigotes of L. infantum as stimulating agent. The kinetics of both groups followed a similar temporal pattern, with higher values in the patient's group. Moreover, we observed that in both groups the activation was dose-dependently inhibited following the addition of gamma 123 anti-IFN-gamma monoclonal antibody. These results indicate the need for IFN-gamma in the activation process of PBMC induced by Leishmania antigens and stress the role of IFN-gamma in the immune response to leishmaniasis. The relevance of the elucidation of the immune response mechanism in human leishmaniasis for therapy and vaccination is briefly discussed.