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The feasibility of obtaining resistant starch type III (RS3) from malanga flour (Xanthosoma sagittifolium), as an unconventional source of starch, was evaluated using the hydrothermal treatment of autoclaving. The physicochemical characterization of RS3 made from malanga flour was carried out through the evaluation of the chemical composition, color attributes, and thermal properties. In addition, the contents of the total starch, available starch, resistant starch, and retrograded resistant starch were determined by in vitro enzymatic tests. A commercial corn starch sample was used to produce RS3 and utilized to compare all of the analyses. The results showed that native malanga flour behaved differently in most of the evaluations performed, compared to the commercial corn starch. These results could be explained by the presence of minor components that could interfere with the physicochemical and functional properties of the flour; however, the RS3 samples obtained from malanga flour and corn starch were similar in their thermal and morphological features, which may be related to their similarities in the content and molecular weight of amylose, in both of the samples. Furthermore, the yields for obtaining the autoclaved powders from corn starch and malanga flour were similar (≈89%), which showed that the malanga flour is an attractive raw material for obtaining RS3 with adequate yields, to be considered in the subsequent research.

Leptospira is a widespread zoonosis that has been linked to transmission between dogs and humans. The main purposes were to determine the seroprevalence of anti-Leptospira serum antibody and to identify the most common serovars in dogs in Spain. This is a cross-sectional study with 1,310 records of canine Leptospira testing data from Spain since 2015 to 2017. Inclusion criteria were individual cases with MAT test results for 8 serovars (Bratislava, Icterohaemorrhagiae, Australis, Pomona, Grippotyphosa, Autumnalis, Canicola and Saxkoebing) and to have the zip code data. Three hundred and thirty-eight samples (25.8%; 95%CI 23.6–28.4) were seropositive (≥1:100). According to geographic areas, North had the highest seroprevalence (38.0%; 95%CI 28.9–47.1) followed by South (29.4%; 95%CI 20.1–38.8), Center (28.6%; 95%CI 24.3–33.0), Mediterranean (22.3%; 95%CI 19.1–25.6) and Northwest (22.2%; 95%CI 7.9–36.4). Seropositivity (MAT ≥1:100) was most common to serovars Icterohaemorrhagiae (19.4%; 95%CI 17.2–21.5) and Bratislava (8.5%; 95%CI 7.0–10.0), followed by Grippotyphosa (7.2%; 95%CI 5.8–8.6), Australis (6.4%; 95%CI 5.0–7.7), Autumnalis (5.0%; 95%CI 3.8–6.2), Pomona (4.5%; 95%CI 3.3–5.6), Canicola (3.4%; 95%CI 2.4–4.4) and Saxkoebing (0.8%; 95%CI 0.3–1.3). An association was found between positivity (MAT ≥1:100) and males (P = 0.003) and dogs that were 6 years old or older were at higher risk of exposure (P = 0.001; OR 4.61; 95%CI 1.86–11.43). This study has shown that dogs in Spain are commonly exposed to Leptospira infection and points out the necessity to control the prevalence of this severe widespread zoonosis in dogs and humans.

This paper describes the development of an application for mobile devices under the iOS platform which has the objective of monitoring patients with alterations or affections from cardiac pathologies. The software tool developed for mobile devices provides a patient and a specialist doctor the ability to handle and treat disease remotely while monitoring through the technique of non-contact photoplethysmography (PPG). The mobile application works by processing red, green, and blue (RGB) color video images on a specific region of the face, thus obtaining the intensity of the pixels in the green channel. The results are then processed using mathematical algorithms and Fourier transform, moving from the time domain to the frequency domain to ensure proper interpretation and to obtain the pulses per minute (PPM). The results are favorable because a comparison of the results was made with respect to the application of a medical-grade pulse-oximeter, where an error rate of 3% was obtained, indicating the acceptable performance of our application. The present technological development provides an application tool with significant potential in the area of health.

Manual measurements of foot anthropometry can lead to errors since this task involves the experience of the specialist who performs them, resulting in different subjective measures from the same footprint. Moreover, some of the diagnoses that are given to classify a footprint deformity are based on a qualitative interpretation by the physician; there is no quantitative interpretation of the footprint. The importance of providing a correct and accurate diagnosis lies in the need to ensure that an appropriate treatment is provided for the improvement of the patient without risking his or her health. Therefore, this article presents a smart sensor that integrates the capture of the footprint, a low computational-cost analysis of the image and the interpretation of the results through a quantitative evaluation. The smart sensor implemented required the use of a camera (Logitech C920) connected to a Raspberry Pi 3, where a graphical interface was made for the capture and processing of the image, and it was adapted to a podoscope conventionally used by specialists such as orthopedist, physiotherapists and podiatrists. The footprint diagnosis smart sensor (FPDSS) has proven to be robust to different types of deformity, precise, sensitive and correlated in 0.99 with the measurements from the digitalized image of the ink mat.

The objective of this work was to investigate the effect of zein and film formulation on mechanical and structural properties of native (FNS), and oxidized with 2.5% (FOSA) and 3.5% (FOSB) banana starch. The oxidized starch showed differences from native starch due to the oxidation process, showing a decrease in lipids, proteins, and amylose. The increase of the sodium hypochlorite increased the content of carbonyl and carboxyl groups in the ranges 0.015–0.028% and 0.022–0.031%, respectively. The film obtained from FOSB displayed the highest tensile strength (5.05 MPa) and satisfactory elongation value (27.1%). The zein addition caused a decrease in these mechanical properties, as well as a significant decrease in water vapour permeability (WVP). However, films from FOSA and FOSB showed higher permeability than that of the native starch. The addition of glycerol and the level of oxidation increased the films moisture. Micrographs showed that, during the oxidation process, impurities were largely eliminated from the starch granule, noting more homogeneous structures both in granules and films.

The risk of progression from Mycobacterium tuberculosis (M.tb) infection to active tuberculosis (TB) disease varies markedly with age. TB disease is significantly less likely in pre-adolescent children above 4 years of age than in very young children or post-pubescent adolescents and young adults. We hypothesized that pro-inflammatory responses to M.tb in pre-adolescent children are either less pronounced or more regulated, than in young adults. Inflammatory and antimicrobial mediators, measured by microfluidic RT-qPCR and protein bead arrays, or by analyzing published microarray data from TB patients and controls, were compared in pre-adolescent children and adults. Multivariate analysis revealed that M.tb-uninfected 8-year-old children had lower levels of myeloid-associated pro-inflammatory mediators than uninfected 18-year-old young adults. Relative to uninfected children, those with M.tb-infection had higher levels of similar myeloid inflammatory responses. These inflammatory mediators were also expressed after in vitro stimulation of whole blood from uninfected children with live M.tb. Our findings suggest that myeloid inflammation is intrinsically lower in pre-pubescent children than in young adults. The lower or more regulated pro-inflammatory responses may play a role in the lower risk of TB disease in this age group.

Eradication of tuberculosis (TB), the world's leading cause of death due to infectious disease, requires a highly efficacious TB vaccine. Many TB vaccine candidates are in pre-clinical and clinical development but only a few can be advanced to large-scale efficacy trials due to limited global resources. We aimed to perform a statistically rigorous comparison of the antigen-specific T cell responses induced by six novel TB vaccine candidates and the only licensed TB vaccine, Bacillus Calmette-Guérin (BCG). We propose that the antigen-specific immune response induced by such vaccines provides an objective, data-driven basis for prioritisation of vaccine candidates for efficacy testing. We analyzed frequencies of antigen-specific CD4 and CD8 T cells expressing IFNγ, IL-2, TNF and/or IL-17 from adolescents or adults, with or without Mycobacterium tuberculosis (M.tb) infection, who received MVA85A, AERAS-402, H1:IC31, H56:IC31, M72/AS01E, ID93+GLA-SE or BCG. Two key response characteristics were analyzed, namely response magnitude and cytokine co-expression profile of the memory T cell response that persisted above the pre-vaccination response to the final study visit in each trial. All vaccines preferentially induced antigen-specific CD4 T cell responses expressing Th1 cytokines; levels of IL-17-expressing cells were low or not detected. In M.tb-uninfected and -infected individuals, M72/AS01E induced higher memory Th1 cytokine-expressing CD4 T cell responses than other novel vaccine candidates. Cytokine co-expression profiles of memory CD4 T cells induced by different novel vaccine candidates were alike. Our study suggests that the T cell response feature which most differentiated between the TB vaccine candidates was response magnitude, whilst functional profiles suggested a lack of response diversity. Since M72/AS01E induced the highest memory CD4 T cell response it demonstrated the best vaccine take. In the absence of immunological correlates of protection, the likelihood of finding a protective vaccine by empirical testing of candidates may be increased by the addition of candidates that induce distinct immune characteristics.

Type 2 diabetes, insulin resistance, and obesity are strongly associated and are a major health problem worldwide. Obesity largely results from a sustained imbalance between energy intake and expenditure. Therapeutic approaches targeting metabolic rate may counteract body weight gain and insulin resistance. Bone morphogenic protein 7 (BMP7) has proven to enhance energy expenditure by inducing non-shivering thermogenesis in short-term studies in mice treated with the recombinant protein or adenoviral vectors encoding BMP7 . To achieve long-term BMP7 effects, the use of adeno-associated viral (AAV) vectors would provide sustained production of the protein after a single administration. Here, we demonstrated that treatment of high-fat-diet-fed mice and ob/ob mice with liver-directed AAV-BMP7 vectors enabled a long-lasting increase in circulating levels of this factor. This rise in BMP7 concentration induced browning of white adipose tissue (WAT) and activation of brown adipose tissue, which enhanced energy expenditure, and reversed WAT hypertrophy, hepatic steatosis, and WAT and liver inflammation, ultimately resulting in normalization of body weight and insulin resistance. This study highlights the potential of AAV-BMP7-mediated gene therapy for the treatment of insulin resistance, type 2 diabetes, and obesity., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Aggregation of α-synuclein is associated with neurodegeneration and a hallmark pathology in synucleinopathies. These aggregates are thought to function as prion-like particles where the conformation of misfolded α-synuclein determines the traits of the induced pathology, similar to prion diseases. Still, little is known about the molecular targets facilitating the conformation-specific biological effects, but their identification could form the basis for new therapeutic interventions. High-throughput screening of annotated compound libraries could facilitate mechanistic investigation by identifying targets with impact on α-synuclein aggregation. To this end, we developed a FRET-based cellular reporter in HEK293T cells, with sensitivity down to 6.5 nM α-synuclein seeds. Using this model system, we identified GF109203X, SB202190, and SB203580 as inhibitors capable of preventing induction of α-synuclein aggregation via inhibition of p38 MAPK and PKC, respectively. We further investigated the mechanisms underlying the protective effects and found alterations in the endo-lysosomal system to be likely candidates of the protection. We found the changes did not stem from a reduction in uptake but rather alteration of lysosomal abundance and degradative capacity. Our findings highlight the value high-throughput screening brings to the mechanistic investigation of α-synuclein aggregation while simultaneously identifying novel therapeutic compounds., (© 2021. The Author(s).)

Malaria liver stage infection is an obligatory parasite development step and represents a population bottleneck in Plasmodium infections, providing an advantageous target for blocking parasite cycle progression. Parasite development inside hepatocytes implies a gross cellular insult evoking innate host responses to counteract intra-hepatocytic infection. Using primary hepatocyte cultures, we investigated the role of Kupffer cell-derived hepatocyte growth factor (HGF) in malaria liver stage infection. We found that Kupffer cells from Plasmodium -infected livers produced high levels of HGF, which trigger apoptosis of infected hepatocytes through a mitochondrial-independent apoptosis pathway. HGF action in infected hepatocyte primary cultures results in a potent reduction of parasite yield by specifically sensitizing hepatocytes carrying established parasite exo-erythrocytic forms to undergo apoptosis. This apoptosis mechanism is distinct from cell death that is spontaneously induced in infected cultures and is governed by Fas signaling modulation through a mitochondrial-dependent apoptosis pathway. This work indicates that HGF and Fas signaling pathways are part of an orchestrated host apoptosis response that occurs during malaria liver stage infection, decreasing the success of infection of individual hepatocytes. Our results raise the hypothesis that paracrine signals derived from Kupffer cell activation are implicated in directing death of hepatocytes infected with the malaria parasite.

Plasmodium liver stage infection is a target of interest for the treatment of and vaccination against malaria. Here we used forward genetics to search for mechanisms underlying natural host resistance to infection and identified triggering receptor expressed on myeloid cells 2 (TREM2) and MHC class II molecules as determinants of Plasmodium berghei liver stage infection in mice. Locus belr1 confers resistance to malaria liver stage infection. The use of newly derived subcongenic mouse lines allowed to map belr1 to a 4-Mb interval on mouse chromosome 17 that contains the Trem2 gene. We show that Trem2 expression in the nonparenchymal liver cells closely correlates with resistance to liver stage infection, implicating TREM2 as a mediator of the belr1 genetic effect. Trem2-deficient mice are more susceptible to liver stage infection than their WT counterparts. We found that Kupffer cells are the principle cells expressing TREM2 in the liver, and that Trem2(-/-) Kupffer cells display altered functional activation on exposure to P. berghei sporozoites. TREM2 expression in Kupffer cells contributes to the limitation of parasite expansion in isolated hepatocytes in vitro, potentially explaining the increased susceptibility of Trem2(-/-) mice to liver stage infection. The MHC locus was also found to control liver parasite burden, possibly owing to the expression of MHC class II molecules in hepatocytes. Our findings implicate unexpected Kupffer-hepatocyte cross-talk in the control Plasmodium liver stage infection and demonstrate that TREM2 is involved in host responses against the malaria parasite.

Natural IgM are involved in numerous immunological functions but the genetic factors that control the homeostasis of its secretion and upholding remain unknown. Prompted by the finding that C57BL/6 mice had significantly lower serum levels of IgM when compared with BALB/c mice, we performed a genome-wide screen and found that the level of serum IgM was controlled by a QTL on chromosome 13 reaching the highest level of association at marker D13Mit266 (LOD score=3.54). This locus was named IgMSC1 and covered a region encompassing the interferon-regulatory factor 4 gene (Irf4). The number of splenic mature B cells in C57BL/6 did not differ from BALB/c mice but we found that low serum levels of IgM in C57BL/6 mice correlated with lower frequency of IgM-secreting cells in the spleen and in the peritoneal cavity. These results suggested that C57BL/6 mice have lower efficiency in late B-cell maturation, a process that is highly impaired in Irf4 knockout mice. In fact, we also found reduced Irf4 gene expression in B cells of C57BL/6 mice. Thus, we propose Irf4 as a candidate for the IgMSC1 locus, which controls IgM homeostatic levels at the level of B-cell terminal differentiation.