Deciphering Structural Traits for Thermal and Kinetic Stability Across Protein Family Evolution through Ancestral Sequence Reconstruction.

Natural proteins are frequently marginally stable, and an increase in environmental temperature can easily lead to unfolding. As a result, protein engineering to improve protein stability is an area of intensive research. Nonetheless, since there is usually a high degree of structural homology between proteins from thermophilic organisms and their mesophilic counterparts, the identification of structural determinants for thermo-adaptation is challenging. Moreover, in many cases, it has become clear that the success of stabilization strategies is often dependent on the evolutionary history of a protein family. In the last few years, the use of ancestral sequence reconstruction (ASR) as a tool for elucidation of the evolutionary history of functional traits of a protein family have gained strength. Here, we used ASR to trace the evolutionary pathways between mesophilic and thermophilic kinases that participate in the biosynthetic pathway of vitamin B1 in bacteria. By combining biophysics approaches, X-ray crystallography, and molecular dynamic simulations, we found that the thermal stability of these enzymes correlate with their kinetic stability, where the highest thermal/kinetic stability is given by an increase in small hydrophobic amino acids that allow a higher number of interatomic hydrophobic contacts, making this type of interaction the main support for stability in this protein architecture. The results highlight the potential benefits of using ASR to explore the evolutionary history of protein sequence and structure to identify traits responsible for the kinetic and thermal stability of any protein architecture.

Decreased clinical performance in TGA-ASO patients after RVOT interventions; a multicenter European collaboration.

BACKGROUND: In patients with transposition of the great arteries and an arterial switch operation (TGA-ASO) right ventricular outflow tract (RVOT) obstruction is a common complication requiring one or more RVOT interventions. OBJECTIVES: We aimed to assess cardiopulmonary exercise capacity and right ventricular function in patients stratified for type of RVOT intervention. METHODS: TGA-ASO patients (≥16 years) were stratified by type of RVOT intervention. The following outcome parameters were included: predicted (%) peak oxygen uptake (peak VO2), tricuspid annular plane systolic excursion (TAPSE), tricuspid Lateral Annular Systolic Velocity (TV S'), right ventricle (RV)-arterial coupling (defined as TAPSE/RV systolic pressure ratio), and N-terminal proBNP (NT-proBNP). RESULTS: 447 TGA patients with a mean age of 25.0 (interquartile range (IQR) 21-29) years were included. Patients without previous RVOT intervention (n = 338, 76%) had a significantly higher predicted peak VO2 (78.0 ± 17.4%) compared to patients with single approach catheter-based RVOT intervention (73.7 ± 12.7%), single approach surgical RVOT intervention (73.8 ± 28.1%), and patients with multiple approach RVOT intervention (66.2 ± 14.0%, p = 0.021). RV-arterial coupling was found to be significantly lower in patients with prior catheter-based and/or surgical RVOT intervention compared to patients without any RVOT intervention (p = 0.029). CONCLUSIONS: TGA patients after a successful arterial switch repair have a decreased exercise capacity. A considerable amount of TGA patients with either catheter or surgical RVOT intervention perform significantly worse compared to patients without RVOT interventions.

Time, temperature and media: the three keys to improve the recovery of Campylobacter fetus subsp. venerealis from preputial bull samples.

The isolation of Campylobacter fetus subsp. venerealis (Cfv) from clinical samples is the gold standard for confirming cases of bovine genital campylobacteriosis, an important cause of infertility in cattle and a potential public health concern. Furthermore, isolation is also necessary for the development of autologous vaccines, characterization of strains for antimicrobial susceptibility patterns, etc. Nevertheless, the sensitivity of culture methods is usually low, and there is no standardized protocol to maximize the recovery of Cfv from clinical samples. The aim of the current study is to design a protocol for the culture of Cfv from preputial samples by evaluating the combination of different transport, enrichment and culture media considering the impact of certain factors (time between collection and enrichment, temperature, and use of filters). The use of modified Lander's transport medium and storing the sample for 24 h at 21 ± 2 °C led to the highest recovery of Cfv CFUs. In contrast, the storage of the samples during 24-48 h in PBS and Thomann rarely allowed the recovery of Cfv regardless of the temperature. The enrichment medium yielding the best results was Preston (significantly higher recovery than Brucella medium), while Cfv could not be isolated with Bolton. Regarding our diagnostic assay (using Lander as transport medium and Preston as enrichment medium), the best protocol in terms of maximizing Cfv recovery as well as limiting contaminations is to culture the samples in i) solid media Preston or Skirrow, and ii) using 0.65 µm filters and incubating plates at 37 °C in microaerophilic conditions.

How adolescents lose control over social networks: A process-based approach to problematic social network use.

Social networks (SNs) are immensely popular, especially among teenagers, yet our understanding of problematic SNs remains limited. Understanding motivations and patterns of use is crucial given the current prevalence of problematic SNs use. Perarles et al. (2020) distinguish two behavioral control modes: Model-Free Control, where actions are characterized by actions driven by immediate gratification without reflective consideration for long-term consequences, and Model-Based Control, enabling planned and goal-directed actions. Both control modes can lead to problematic social network use. This study aims to delve into problematic SNs use and the underlying motives behind adolescents' participation in SNs, drawing upon the theoretical proposal by Perales et al. (2020). We conducted four focus groups with adolescents aged 13-17 (50 % female; Mage = 14.5, SD = 1.75), comprising two public school and two Catholic private school groups. Thematic analysis using Atlas.ti software revealed three themes. The first uncovers characteristics of problematic SNs use, including withdrawal, increased usage time, impaired control, behavioral salience and attentional capture and cognitive hijacking. The second spotlights motives, emphasizing emotional regulation, finding out what is going on, and social interaction. The third theme explores consequences such as compromised academic performance and physical harm. In conclusion, addressing both motives and problematic behaviors present a more effective approach to confronting SNs use challenges and fostering healthier online experiences for adolescents.

Structural insights into a functional unit from an immunogenic mollusk hemocyanin.

Mollusk hemocyanins, among the largest known proteins, are used as immunostimulants in biomedical and clinical applications. The hemocyanin of the Chilean gastropod Concholepas concholepas (CCH) exhibits unique properties, which makes it safe and effective for human immunotherapy, as observed in animal models of bladder cancer and melanoma, and dendritical cell vaccine trials. Despite its potential, the structure and amino acid sequence of CCH remain unknown. This study reports two sequence fragments of CCH, representing three complete functional units (FUs). We also determined the high-resolution (1.5 Å) X-ray crystal structure of an "FU-g type" from the CCHB subunit. This structure enables in-depth analysis of chemical interactions at the copper-binding center and unveils an unusual, truncated N-glycosylation pattern. These features are linked to eliciting more robust immunological responses in animals, offering insights into CCH's enhanced immunostimulatory properties and opening new avenues for its potential applications in biomedical research and therapies.

Histoplasma antigens as novel players for the development of new enzyme immunoassays for the serodiagnosis of histoplasmosis: A comparative study of their analytical performance.

Definitive diagnosis of histoplasmosis relies on culture and/or cytology/histopathology; however, these procedures have limited sensitivity and cultures are time-consuming. Antibodies detection by immunodiffusion has low sensitivity in immunocompromised individuals and uses histoplasmin (HMN), a crude antigenic extract, as reagent. Novel protein antigen candidates have been recently identified and produced by DNA-recombinant techniques to obtain standardized and specific reagents for diagnosing histoplasmosis. To compare the analytical performance of novel enzyme-linked immunosorbent assays (ELISAs) for antibodies testing for diagnosing histoplasmosis using different Histoplasma capsulatum antigens as reagents. The H. capsulatum 100 kDa protein (Hcp100), the M antigen and its immunoreactive fragment F1 were produced by DNA-recombinant techniques. Galactomannan was purified from both the yeast and mycelial cell walls (yGM and mGM, respectively). The analytical performance of the ELISA tests for the serological detection of antibodies against these antigens was evaluated and compared with those obtained using HMN as reagent. Antibodies detection by the Hcp100 ELISA demonstrated 90.0% sensitivity and 92.0% specificity, versus 43.3% sensitivity and 95.0% specificity of the M ELISA, 33.3% sensitivity and 84.0% specificity of the F1 ELISA, 96.7% sensitivity and 94.0% specificity of the yGM ELISA, 83.3% sensitivity and 88.0% specificity of the mGM ELISA, and 70.0% sensitivity and 86.0% specificity for the HMN ELISA. In summary, Hcp100 is proposed as the most promising candidate for the serodiagnosis of histoplasmosis. The primary immunoreactive element in HMN proved to be GM rather than the M antigen. Nevertheless, a higher incidence of cross-reactions was noted with GM compared to M.

Hcp100 is a promising serodiagnostic candidate for histoplasmosis, boasting high sensitivity and specificity. Notably, GM, rather than M antigen, emerged as the primary immunoreactive element in HMN, despite a higher incidence of cross-reactions with GM compared to M.

Biomarkers for response to TIL therapy: a comprehensive review.

Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) has demonstrated durable clinical responses in patients with metastatic melanoma, substantiated by recent positive results of the first phase III trial on TIL therapy. Being a demanding and logistically complex treatment, extensive preclinical and clinical effort is required to optimize patient selection by identifying predictive biomarkers of response. This review aims to comprehensively summarize the current evidence regarding the potential impact of tumor-related factors (such as mutational burden, neoantigen load, immune infiltration, status of oncogenic driver genes, and epigenetic modifications), patient characteristics (including disease burden and location, baseline cytokines and lactate dehydrogenase serum levels, human leucocyte antigen haplotype, or prior exposure to immune checkpoint inhibitors and other anticancer therapies), phenotypic features of the transferred T cells (mainly the total cell count, CD8:CD4 ratio, ex vivo culture time, expression of exhaustion markers, costimulatory signals, antitumor reactivity, and scope of target tumor-associated antigens), and other treatment-related factors (such as lymphodepleting chemotherapy and postinfusion administration of interleukin-2).

Metal Ions Can Modulate the Self-Assembly and Activity of Catalytic Peptide Amyloids.

Rational design of peptides has become a powerful tool to produce self-assembled nanostructures with the ability to catalyze different chemical reactions, paving the way to develop minimalistic enzyme-like nanomaterials. Catalytic amyloid-like assemblies have emerged among the most versatile and active, but they often require additional factors for activity. Elucidating how these factors influence the structure and activity is key for the design. Here, we showed that biologically relevant metal ions can guide and modulate the self-assembly of a small peptide into diverse amyloid architectures. The morphology and catalytic activity of the resulting fibrils were tuned by the specific metal ion decorating the surface, whereas X-ray structural analysis of the amyloids showed ion-dependent shape sizes. Molecular dynamics simulations showed that the metals can strongly affect the local conformational space, which can trigger major rearrangements of the fibrils. Our results demonstrate that the conformational landscape of catalytic amyloids is broad and tunable by external factors, which can be critical for future design strategies.

Investigating epidemiological distribution (temporality and intensity) of respiratory pathogens following COVID-19 de-escalation process in Catalonia, September 2016-June 2021: Analysis of regional surveillance data.

BACKGROUND: Following the low incidence rates of non-SARS-CoV-2 respiratory viruses registered during the strict lockdown enforced in the pandemic, a resurgence of several endemic viruses in Catalonia (Spain) was noted during the early summer of 2021. OBJECTIVES: In this study, we investigated whether the circulation of non-SARS-CoV-2 respiratory viruses in Catalonia, assessed by Microbiological Reporting System of Catalonia (MRSC) and the Epidemiological Surveillance Network of Catalonia, was affected by the strict lockdown measures, as well as, the implication of the Coronavirus Disease 19 (COVID-19) de-escalation process in the late season outbreaks registered during the 2020-2021 season. STUDY DESIGN: A retrospective comparison of epidemic patterns in the respiratory viruses' incidence, using regional public health surveillance data from MRSC, was performed between weeks 26/2016 to week 27/2021. Data were expressed as the weekly total number of test positivity for individual viruses. A segmented negative binomial regression model was conducted, with two parameters included (level and trend) for each segment of the time series (2020 pre-lockdown, 2020 post-lockdown and 2021). Results were reported as a unit changed in the strict lockdown. RESULTS: A total of 51588 confirmed cases of the different respiratory viruses were included in the analysis, the majority were influenza cases (63.7%). An immediate reduction in the weekly number of cases was observed in 2020 after the COVID-19 outbreak for human adenovirus virus (HAdV) (ß2 = -2.606; P <0.01), human parainfluenza virus (HPIV) (ß2 = -3.023; P <0.01), influenza virus (IFV) (ß2 = -1.259; P <0.01), but not for respiratory syncytial virus (RSV), where the number of cases remained unchanged. During 2020, a significant negative trend was found for RSV (ß3 = -0.170, P <0.01), and a positive trend for HAdV (ß3 = 0.075, P <0.01). During 2021, a significant reduction in the weekly number of cases was also observed for all respiratory viruses, and a borderline non-significant reduction for HPIV (ß3 = -0.027; P = 0.086). Moreover, significant positive trends were found for each viral pathogen, except for influenza during 2020-2021 season, where cases remained close to zero. The respiratory viruses increased activity and their late season epidemic start particularly affected children under 6 years old. CONCLUSIONS: Our data not only provides evidence that occurrence of different respiratory virus infections was affected by the strict lockdown taken against SARS-CoV-2 but it also shows a late resurgence of seasonal respiratory viruses' cases during the 2020-2021 season following the relaxation of COVID-19-targeted non-pharmaceutical interventions.

Case report: Efficacy of immunotherapy as conversion therapy in dMMR/MSI-H colorectal cancer: a case series and review of the literature.

Immunotherapy has demonstrated a role in the therapeutic landscape of a small subset of patients with colorectal carcinoma (CRC) that harbor a microsatellite instability (MSI-H) status due to a deficient DNA mismatch repair (dMMR) system. The remarkable responses to immune checkpoint inhibitors (ICIs) are now being tested in the neoadjuvant setting in localized CRC, where the dMMR/MSI-H status can be found in up to 15% of patients, with remarkable results obtained in NICHE2 and 3 trials, among others. This case series aims to report our experience at a tertiary center and provide a comprehensive analysis of the possible questions and challenges to overcome if ICIs were established as standard of care in a neoadjuvant setting, as well as the potential role they may have as conversion therapy not only in locoregional advanced CRC but also in oligometastatic disease.

Comparative removal of pharmaceuticals in aqueous phase by agricultural waste-based biochars.

The intensification of pharmaceutical use globally has led to an increase in the number of water bodies contaminated by drugs, and an effective strategy must be developed to address this issue. In this work, several biochars produced from Miscanthus straw pellets (MSP550, MSP700) and wheat straw pellets (WSP550, WSP700) at 550 and 700°C, respectively, were selected as adsorbents for removing various pharmaceuticals, such as pemetrexed (PEME), sulfaclozine (SCL), and terbutaline (TBL), from the aqueous phase. The biochar characterizations (physicochemical properties, textural properties, morphological structures, and zeta potentials) and adsorptive conditions (contact times, temperatures, and pH effect) were investigated. The infrared and Raman spectra of biochars before and after pharmaceutical adsorption, as well as quantum chemical computations, were carried out to explore the adsorption mechanisms. The results showed that the general adsorption abilities of biochars for pharmaceuticals were in the order of WSP700 > MSP700 > MSP550 > WSP550. Both the higher drug concentration and higher temperature improved biochar adsorption. By decreasing the pH, the adsorption amounts increased for PEME and SCL. However, TBL exhibited the best adsorption at pH 7, whereas a weakening of affinity occurred at lower or higher pH values. Electrostatic interactions and hydrogen bonding were the main adsorptive mechanisms between all biochars and pharmaceuticals. π-π interactions played a role in the adsorption process of low-temperature-prepared biochars (MSP550 and WSP550). This work can provide new insights into the control of pharmaceuticals from water with low-cost adsorbents. PRACTITIONER POINTS: Use of biochars for pharmaceuticals removal from aqueous phase. Characterization of biochars : physical and chemical properties, textural and surface properties. Simulation calculation for characterization of pharmaceuticals. Kinetic studies of pharmaceuticals adsorption on biochars. DRIFTS and Raman analysis for the understanding of adsorption process.

Antibiotic point prevalence survey and antimicrobial resistance in hospitalized patients across Peruvian reference hospitals.

BACKGROUND: Peru reports higher levels than other countries in Latin America of resistance to antimicrobials among Gram-positive and Gram-negative bacteria, however data on antibiotic use in Peru are scarce. This study aims to estimate the prevalence and quality of antibiotic prescription in hospitalized patients and to determine the antibiotic susceptibility rates of bacteria causing key bacterial infections. METHODS: We carried out a point prevalence survey of antibiotic prescription at ten public hospitals in nine regions of Peru. Data was collected from patients hospitalized during a 3-week period, with details about antibiotic use, patient information, and antimicrobial susceptibility. RESULTS: 1620 patient charts were reviewed; in 924 cases antibiotics were prescribed (57.0 %, range 45.9-78.9 %). Most of the antibiotics (74.2 %) were prescribed as empirical treatment, only 4.4 % as targeted treatment. For 9.5 % of cases the reason for antibiotic use was unknown. Cephalosporins were the most prescribed (30.0 %), followed by carbapenems (11.3 %). Ninety-four blood cultures were positive for bacterial growth, 48.8 % of the Staphylococcus aureus were methicillin-resistant, among Escherichia coli and Klebsiella pneumoniae, 51.7 % and 72.7 % were resistant to third-generation cephalosporins (3GC), 3.4 % and 18.2 % were resistant to carbapenems, respectively. Among bacteria isolated from urine cultures (n = 639), 43.9 % of E. coli and 49.2 % of K. pneumoniae were resistant to 3GC, and 0.9 % of E. coli and 3.2 % of K. pneumoniae were resistant to meropenem. CONCLUSIONS: The overall proportion of hospitalized patients receiving antibiotics in hospitals from different regions in Peru was high, with only a small proportion receiving targeted treatment. Cephalosporins and carbapenems were the most frequently prescribed antibiotics, reflecting high resistance rates against 3GC and carbapenems in Enterobacterales isolated from blood and urine.

Methicillin-Resistant Staphylococcus aureus Bloodstream Infections in Hospitalized Patients in Peru.

There is a knowledge gap in the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) causing bloodstream infections (BSIs) in Peru. Through a surveillance study in 13 hospitals of 10 Peruvian regions (2017-2019), we assessed the proportion of MRSA among S. aureus BSIs as well as the molecular typing of the isolates. A total of 166 S. aureus isolates were collected, and 36.1% of them were MRSA. Of note, MRSA isolates with phenotypic and genetic characteristics of the hospital-associated Chilean-Cordobes clone (multidrug-resistant SCCmec I, non-Panton-Valentine leukocidin [PVL] producers) were most commonly found (70%), five isolates with genetic characteristics of community-associated MRSA (CA-MRSA)-SCCmec IV, PVL-producer-(8.3%) were seen in three separate regions. These results demonstrate that hospital-associated MRSA is the most frequent MRSA found in patients with BSIs in Peru. They also show the emergence of S. aureus with genetic characteristics of CA-MRSA. Further studies are needed to evaluate the extension of CA-MRSA dissemination in Peru.

Prevalence of Antimicrobial Resistance in Gram-Negative Bacteria Bloodstream Infections in Peru and Associated Outcomes: VIRAPERU Study.

Surveillance of antimicrobial resistance among gram-negative bacteria (GNB) is of critical importance, but data for Peru are not available. To fill this gap, a non-interventional hospital-based surveillance study was conducted in 15 hospitals across Peru from July 2017 to October 2019. Consecutive unique blood culture isolates of key GNB (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter spp.) recovered from hospitalized patients were collected for centralized antimicrobial susceptibility testing, along with linked epidemiological and clinical data. A total of 449 isolates were included in the analysis. Resistance to third-generation cephalosporins (3GCs) was present in 266 (59.2%) GNB isolates. Among E. coli (n = 199), 68.3% showed 3GC resistance (i.e., above the median ratio for low- and middle-income countries in 2020 for this sustainable development goal indicator). Carbapenem resistance was present in 74 (16.5%) GNB isolates, with wide variation among species (0% in E. coli, 11.0% in K. pneumoniae, 37.0% in P. aeruginosa, and 60.8% in Acinetobacter spp. isolates). Co-resistance to carbapenems and colistin was found in seven (1.6%) GNB isolates. Empiric treatment covered the causative GNB in 63.3% of 215 cases. The in-hospital case fatality ratio was 33.3% (92/276). Pseudomonas aeruginosa species and carbapenem resistance were associated with higher risk of in-hospital death. In conclusion, an important proportion of bloodstream infections in Peru are caused by highly resistant GNB and are associated with high in-hospital mortality.

Human genetic adaptation related to cellular zinc homeostasis.

SLC30A9 encodes a ubiquitously zinc transporter (ZnT9) and has been consistently suggested as a candidate for positive selection in humans. However, no direct adaptive molecular phenotype has been demonstrated. Our results provide evidence for directional selection operating in two major complementary haplotypes in Africa and East Asia. These haplotypes are associated with differential gene expression but also differ in the Met50Val substitution (rs1047626) in ZnT9, which we show is found in homozygosis in the Denisovan genome and displays accompanying signatures suggestive of archaic introgression. Although we found no significant differences in systemic zinc content between individuals with different rs1047626 genotypes, we demonstrate that the expression of the derived isoform (ZnT9 50Val) in HEK293 cells shows a gain of function when compared with the ancestral (ZnT9 50Met) variant. Notably, the ZnT9 50Val variant was found associated with differences in zinc handling by the mitochondria and endoplasmic reticulum, with an impact on mitochondrial metabolism. Given the essential role of the mitochondria in skeletal muscle and since the derived allele at rs1047626 is known to be associated with greater susceptibility to several neuropsychiatric traits, we propose that adaptation to cold may have driven this selection event, while also impacting predisposition to neuropsychiatric disorders in modern humans.

High-Fiber Diet and Crohn's Disease: Systematic Review and Meta-Analysis.

Crohn's disease (CD) is a subtype of inflammatory bowel disease (IBD). CD is a health problem in Western countries such as the US and European nations and is an idiopathic disease; however, certain cases of CD have been associated with intestinal dysbiosis. A systematic review with a meta-analysis was carried out to determine the efficacy of a diet rich in fiber with or without cointervention to improve remission rates for CD. The literature in the PubMed, Scopus, Web of Science, and ClinicalTrials databases was reviewed. The quality of the studies was evaluated using the Johanna Briggs Institute (JBI) scale. This review was conducted in accordance with the structure outlined in the PRISMA statement. In addition, a meta-analysis was performed with a 95% confidence interval (CI) and a random effects model. Eleven studies were included, totaling 2389 patients with CD. Applying a diet rich in fiber with or without the administration of routine therapies improved CD remission rates. Data regarding CD activity, remission time, and adverse effects derived from fiber consumption were analyzed. Consumption of fiber in the diet could improve remission rates for CD patients who receive or do not receive other treatment to maintain remission.

Isolated Fraction of Gastric-Digested Camel Milk Yogurt with Carao (Cassia grandis) Pulp Fortification Enhances the Anti-Inflammatory Properties of HT-29 Human Intestinal Epithelial Cells.

Functional foods have recently generated a lot of attention among consumers looking for healthy options. Studies have examined yogurt with carao to increase health benefits and probiotic characteristics. It has been determined that carao fruit and camel milk have high phenolic compound and antioxidant activity concentrations. The objective of this study was to examine if carao (0, 1.3, 2.65, and 5.3 g/L) incorporated into yogurt enhances anti-inflammatory stimulus and antioxidant activity and impacts the physio-chemical and sensory properties of camel milk yogurt. HT-29 cells were used as a model of anti-inflammatory response, including cytokine responses of IL-8 and mRNA production of IL-1ß and TNF-α in gastric digested isolated fraction. In addition, pH, titratable acidity, Streptococcus thermophilus counts and Lactobacillus bulgaricus counts of camel yogurts were examined during the fermentation process in 0, 2.5, 5, and 7 h whereas viscosity, syneresis, and radical scavenging assay evaluations were determined at hour 7. Furthermore, a consumer study was performed. Compared to control samples, the incorporation of carao into yogurts did not lead to a significant (ρ > 0.05) difference in the pH. In contrast, titratable acidity (TA), viscosity, syneresis, and antioxidant capacity significantly increased with the inclusion of 2.65 and 5.3 g/L carao, while 5.3 g/L carao significantly (ρ < 0.05) increased the counts of both bacteria. The inflammatory response of IL-8 and the level of mRNA production of IL-1ß and TNF-α was significantly (ρ < 0.05) lower with 2.65 and 5.3 g/L carao yogurt compared to control camel yogurt. Sensory attributes were not impacted by the addition of 1.3 and 2.65 g/L carao. Carao could be a possible ingredient to consider when improving the nutrition value of yogurt.

Wearable Sports Technology Development in Costa Rica: Inertial Measurement Unit Integration for Real-Time External Load Monitoring / Desarrollo de tecnología deportiva portátil en Costa Rica: integración de una unidad de medición inercial para monitoreo de carga externa en tiempo real / Desenvolvimento de tecnologia desportiva portátil na Costa Rica: integração de uma unidade de medição por inércia para monitorização da carga externa em tempo real

Abstract: The increasing trend and projection for the use of wearable sensors technology in the general population have led to the development of different inertial measurement units (IMU) to monitor activity and motion variables during exercise or sports. This study aims to systematize the practical experience of developing an inertial measurement device to quantify external load in real time for runners. This article shows the installed capacity of Costa Rican higher education institutions to integrate existing sensors available in the international market in a single device to program it and use it for different sport science purposes. Two scientific laboratories joined resources and integrated an interdisciplinary team composed of exercise physiologists, sports scientists, physiotherapists, and electromechanical engineers who globally faced the challenge of creating SafeRun IMU. In this case, an IMU was constructed with great success, capable of quantifying external load variables controlled from a mobile device in real-time. The results showed an acceptable agreement and reliability of the data extracted from the IMU. The information collected from this IMU could be used to control and quantify external load to develop or redirect exercise programming and prescription and prevent overuse injuries or physical overload conditions. This device differs from other existing ones due to its small size and portability, which benefits its commercialization and massification.

Resumen: La creciente tendencia y proyección para el uso de tecnología de sensores portátiles en la población en general ha llevado al desenvolvimiento de diferentes dispositivos de medición inercial, para monitorear las variables de actividad y movimiento durante el ejercicio o los deportes. El objetivo del presente estudio es sistematizar la experiencia práctica de desarrollar un dispositivo de medición inercial, con el fin de cuantificar la carga externa en tiempo real para los corredores. Este artículo demostró la capacidad instalada de las instituciones de educación superior de Costa Rica para integrar los sensores existentes disponibles en el mercado internacional en un solo dispositivo, con el propósito de programarlo y usarlo en diferentes fines de ciencias del deporte. Dos laboratorios científicos unieron esfuerzos e integraron un equipo interdisciplinario compuesto por fisiólogos del ejercicio, científicos del deporte, fisioterapeutas e ingenieros electromecánicos, quienes, de manera global, afrontaron el reto de la creación de la IMU. En este caso, se desarrolló una IMU con gran éxito, capaz de cuantificar las variables de carga externa controladas desde un dispositivo móvil en tiempo real. Los resultados mostraron un nivel de concordancia y fiabilidad aceptable de los datos extraídos de la IMU. La información obtenida de esta IMU podría usarse para controlar y cuantificar la carga externa, con miras a desplegar o redirigir la programación y prescripción de ejercicios, así como con el afán de prevenir lesiones por sobreuso o condiciones de sobrecarga física.

Resumo: A crescente tendência e projeção para o uso da tecnologia de sensores portáteis na população em geral levou ao desenvolvimento de diferentes dispositivos de medição inercial para monitorar as variáveis de atividade e de movimento durante o exercício ou esportes. O objetivo do presente estudo é sistematizar a experiência prática de desenvolvimento de um dispositivo de medição inercial, a fim de quantificar a carga externa em tempo real para os corredores. Este artigo demonstrou a capacidade instalada das instituições de ensino superior da Costa Rica para integrar os sensores existentes disponíveis no mercado internacional em um único dispositivo, com a finalidade de programá-lo e usá-lo para diferentes fins de ciência do esporte. Dois laboratórios científicos uniram forças e integraram uma equipe interdisciplinar composta por fisiologistas do exercício, cientistas do esporte, fisioterapeutas e engenheiros eletromecânicos, que, de forma global, enfrentaram o desafio de criar a IMU. Neste caso, foi desenvolvida uma IMU de grande sucesso, capaz de quantificar variáveis de carga externas controladas a partir de um dispositivo móvel em tempo real. Os resultados mostraram um nível aceitável de concordância e confiabilidade dos dados extraídos da IMU. As informações obtidas desta IMU poderiam ser utilizadas para monitorar e quantificar a carga externa, com o objetivo de implantar ou redirecionar a programação e prescrição de exercícios, bem como com o objetivo de evitar lesões por uso excessivo ou condições de sobrecarga física.

Unraveling the folding and dimerization properties of the human FoxP subfamily of transcription factors.

Human FoxP proteins share a highly conserved DNA-binding domain that dimerizes via three-dimensional domain swapping, although showing varying oligomerization propensities among its members. Here, we present an experimental and computational characterization of all human FoxP proteins to unravel how their amino acid substitutions impact their folding and dimerization mechanism. We solved the crystal structure of the forkhead domain of FoxP4 to then perform a comparison across all members, finding that their sequence changes impact not only the structural heterogeneity of their forkhead domains but also the protein-protein association energy barrier. Lastly, we demonstrate that the accumulation of a monomeric intermediate is an oligomerization-dependent feature rather than a common aspect of monomers and dimers in this protein subfamily.