Bartender: Martini 3 Bonded Terms via Quantum Mechanics-Based Molecular Dynamics.

Coarse-grained (CG) molecular dynamics (MD) simulations have grown in applicability over the years. The recently released version of the Martini CG force field (Martini 3) has been successfully applied to simulate many processes, including protein-ligand binding. However, the current ligand parametrization scheme is manual and requires an a priori reference all-atom (AA) simulation for benchmarking. For systems with suboptimal AA parameters, which are often unknown, this translates into a CG model that does not reproduce the true dynamical behavior of the underlying molecule. Here, we present Bartender, a quantum mechanics (QM)/MD-based parametrization tool written in Go. Bartender harnesses the power of QM simulations and produces reasonable bonded terms for Martini 3 CG models of small molecules in an efficient and user-friendly manner. For small, ring-like molecules, Bartender generates models whose properties are indistinguishable from the human-made models. For more complex, drug-like ligands, it is able to fit functional forms beyond simple harmonic dihedrals and thus better captures their dynamical behavior. Bartender has the power to both increase the efficiency and the accuracy of Martini 3-based high-throughput applications by producing numerically stable and physically realistic CG models.

Exploring Microbial Influence on Flavor Development during Coffee Processing in Humid Subtropical Climate through Metagenetic-Metabolomics Analysis.

Research into microbial interactions during coffee processing is essential for developing new methods that adapt to climate change and improve flavor, thus enhancing the resilience and quality of global coffee production. This study aimed to investigate how microbial communities interact and contribute to flavor development in coffee processing within humid subtropical climates. Employing Illumina sequencing for microbial dynamics analysis, and high-performance liquid chromatography (HPLC) integrated with gas chromatography-mass spectrometry (GC-MS) for metabolite assessment, the study revealed intricate microbial diversity and associated metabolic activities. Throughout the fermentation process, dominant microbial species included Enterobacter, Erwinia, Kluyvera, and Pantoea from the prokaryotic group, and Fusarium, Cladosporium, Kurtzmaniella, Leptosphaerulina, Neonectria, and Penicillium from the eukaryotic group. The key metabolites identified were ethanol, and lactic, acetic, and citric acids. Notably, the bacterial community plays a crucial role in flavor development by utilizing metabolic versatility to produce esters and alcohols, while plant-derived metabolites such as caffeine and linalool remain stable throughout the fermentation process. The undirected network analysis revealed 321 interactions among microbial species and key substances during the fermentation process, with Enterobacter, Kluyvera, and Serratia showing strong connections with sugar and various volatile compounds, such as hexanal, benzaldehyde, 3-methylbenzaldehyde, 2-butenal, and 4-heptenal. These interactions, including inhibitory effects by Fusarium and Cladosporium, suggest microbial adaptability to subtropical conditions, potentially influencing fermentation and coffee quality. The sensory analysis showed that the final beverage obtained a score of 80.83 ± 0.39, being classified as a specialty coffee by the Specialty Coffee Association (SCA) metrics. Nonetheless, further enhancements in acidity, body, and aftertaste could lead to a more balanced flavor profile. The findings of this research hold substantial implications for the coffee industry in humid subtropical regions, offering potential strategies to enhance flavor quality and consistency through controlled fermentation practices. Furthermore, this study contributes to the broader understanding of how microbial ecology interplays with environmental factors to influence food and beverage fermentation, a topic of growing interest in the context of climate change and sustainable agriculture.

Cerebral blood flow regulation and cognitive performance in hypertension.

We examined the relation between transcranial Doppler (TCD) markers of cerebral blood flow regulation and cognitive performance in hypertension (HT) patients to evaluate the predictive value of these markers for cognitive decline. We assessed dynamic cerebral autoregulation (dCA), vasoreactivity to carbon dioxide, and neurovascular coupling (NVC) in the middle (MCA) and posterior (PCA) cerebral arteries of 52 patients. Neuropsychological evaluation included the Montreal Cognitive Assessment and tests covering attention, executive function, processing speed, and memory. Notably, reduced rate time in the PCA significantly predicted better processing speed (p = 0.003). Furthermore, reduced overshoot systolic cerebral blood velocity in the PCA and reduced phase in the VLF range in the MCA (p = 0.021 and p = 0.017, respectively) significantly predicted better memory. Intriguingly, enhanced dCA in the MCA predicted poorer memory performance, while reduced NVC in the PCA predicted both superior processing speed and memory performance. These findings suggest that HT-induced changes in cerebral hemodynamics impact cognitive performance. Further research should verify these observations and elucidate whether these changes represent adaptive responses or neurovascular inefficiency. TCD markers might provide insights into HT-related cognitive decline.

Assessing the Martini 3 protein model: A review of its path and potential.

Coarse-grained (CG) protein models have become indispensable tools for studying many biological protein details, from conformational dynamics to the organization of protein macro-complexes, and even the interaction of proteins with other molecules. The Martini force field is one of the most widely used CG models for bio-molecular simulations, partly because of the enormous success of its protein model. With the recent release of a new and improved version of the Martini force field - Martini 3 - a new iteration of its protein model was also made available. The Martini 3 protein force field is an evolution of its Martini 2 counterpart, aimed at improving many of the shortcomings that had been previously identified. In this mini-review, we first provide a general overview of the model and then focus on the successful advances made in the short time since its release, many of which would not have been possible before. Furthermore, we discuss reported limitations, potential directions for model improvement and comment on what the likely future development and application avenues are.

Exploring diversity and functional traits of lactic acid bacteria in traditional vinegar fermentation: A review.

Vinegar has been used for centuries as a food preservative, flavor enhancer, and medicinal agent. While commonly known for its sour taste and acidic properties due to acetic acid bacteria metabolism, vinegar is also home to a diverse community of lactic acid bacteria (LAB). The main genera found during natural fermentation include Lactobacillus, Lacticaseibacillus, Lentilactobacillus, Limosilactbacillus, Leuconostoc, and Pedicoccus. Many of the reported LAB species fulfill the probiotic criteria set by the World Health Organization (WHO). However, it is crucial to acknowledge that LAB viability undergoes a significant reduction during vinegar fermentation. While containing LAB, none of the analyzed vinegar met the minimum viable amount required for probiotic labeling. To fully unlock the potential of vinegar as a probiotic, investigations should be focused on enhancing LAB viability during vinegar fermentation, identifying strains with probiotic properties, and establishing appropriate dosage and consumption guidelines to ensure functional benefits. Currently, vinegar exhibits substantial potential as a postbiotic product, attributed to the high incidence and growth of LAB in the initial stages of the fermentation process. This review aims to identify critical gaps and address the essential requirements for establishing vinegar as a viable probiotic product. It comprehensively examines various relevant aspects, including vinegar processing, total and LAB diversity, LAB metabolism, the potential health benefits linked to vinegar consumption, and the identification of potential probiotic species.

Rational Prediction of PROTAC-Compatible Protein-Protein Interfaces by Molecular Docking.

Proteolysis targeting chimeras (PROTACs) are heterobifunctional ligands that mediate the interaction between a protein target and an E3 ligase, resulting in a ternary complex, whose interaction with the ubiquitination machinery leads to target degradation. This technology is emerging as an exciting new avenue for therapeutic development, with several PROTACs currently undergoing clinical trials targeting cancer. Here, we describe a general and computationally efficient methodology combining restraint-based docking, energy-based rescoring, and a filter based on the minimal solvent-accessible surface distance to produce PROTAC-compatible PPIs suitable for when there is no a priori known PROTAC ligand. In a benchmark employing a manually curated data set of 13 ternary complex crystals, we achieved an accuracy of 92% when starting from bound structures and 77% when starting from unbound structures, respectively. Our method only requires that the ligand-bound structures of the monomeric forms of the E3 ligase and target proteins be given to run, making it general, accurate, and highly efficient, with the ability to impact early-stage PROTAC-based drug design campaigns where no structural information about the ternary complex structure is available.

Domínios e facetas da qualidade de vida de pessoas idosas segundo a prática sexual / Domains and facets of the quality of life of olders adults according to sexual practice

A pesquisa objetivou comparar os domínios e facetas da qualidade de vida de idosos segundo a prática de relação sexual nos últimos seis meses. Estudo quantitativo, transversal e observacional realizado com 219 idosos de um município do Estado de Minas Gerais. Aplicaram-se os instrumentos WHOQoL-Bref e WHOQoL-Old para a coleta de dados referentes à qualidade de vida, e o teste Mann-Whitney (p < 0,05) para análise. Os domínios físico (p = 0,002), psicológico (p < 0,001) e relações sociais (p < 0,001), e as facetas atividades passadas, presentes e futuras (p = 0,013), participação social (p = 0,007) e intimidade (p = 0,018) estiveram associados à prática de relação sexual nos últimos seis meses, com maiores escores entre aqueles que referiram ser ativos sexualmente.

The objective of this study was to compare the domains and facets of quality of life of older adults, according to the practice of sexual intercourse in the last six months. Quantitative, cross-sectional and observational study, carried out with 219 elderly from a municipality in the State of Minas Gerais. The WHOQoL-Bref and WHOQoL-Old instruments were used to collect data regarding quality of life and the Mann-Whitney test (p < 0.05) for analysis. In the physical (p = 0.002), psychological (p < 0.001) and social relations (p < 0.001) domains, and in the facets past, present and future activities (p = 0.013), social participation (p = 0.007) and intimacy (p = 0.018) were associated with the practice of sexual intercourse in the last six months, with higher scores among those who reported being sexually active.

Brazilian artisanal Colonial cheese: characterization, microbiological safety, and survival of Salmonella enterica serovar Enteritidis during ripening.

The artisanal Colonial cheese is typical of the southern region of Brazil and dates back to the colonization by Italian and German immigrants. Produced with raw milk, it is the main cheese produced by more than 15,200 small rural proprieties. The consumer increasingly appraises food with territorial valorization, demanding specific sanitary norms for this type of cheese. This work aimed to know the physical-chemical characteristics of the cheeses produced in the west of Santa Catarina State, to study the ripening time to reach microbiological safety, and to experimentally observe the survival of Salmonella enterica serovar Enteritidis ATCC 13076 during the ripening. The physical-chemical characterization was performed with 129 samples of cheeses. Five dairies were selected for evaluation of the ripening process. Salmonella survival using a challenge test was performed on three batches prepared in a pilot plant. The cheeses were classified as high (15.4%), medium (74.6%), and low moisture (9.2%), and concerning fat content as semi-fat (37.5%) and fat (62.5%). Salmonella challenge test demonstrated their survival for up to 28 days, depending on the initial contamination. The ripening monitoring showed that thermotolerant coliforms could be a good indicator of the process because they are the most persistent microorganisms.

Emerging contaminants bioremediation by enzyme and nanozyme-based processes - A review.

Due to their widespread occurrence and the inadequate removal efficiencies by conventional wastewater treatment plants, emerging contaminants (ECs) have recently become an issue of great concern. Current ongoing studies have focused on different physical, chemical, and biological methods as strategies to avoid exposing ecosystems to significant long-term risks. Among the different proposed technologies, the enzyme-based processes rise as green biocatalysts with higher efficiency yields and lower generation of toxic by-products. Oxidoreductases and hydrolases are among the most prominent enzymes applied for bioremediation processes. The present work overviews the state of the art of recent advances in enzymatic processes during wastewater treatment of EC, focusing on recent innovations in terms of applied immobilization techniques, genetic engineering tools, and the advent of nanozymes. Future trends in the enzymes immobilization techniques for EC removal were highlighted. Research gaps and recommendations on methods and utility of enzymatic treatment incorporation in conventional wastewater treatment plants were also discussed.

Fine resolution analysis of bacterial communities associated with Neochloris oleoabundans culture and insights into terpenes as contamination control agents.

Biological contamination is one of the main bottlenecks in microalgae production, reducing quality and productivity and sometimes leading to the complete loss of the cultures. Selecting terpenes can be a pathway toward eco-friendly contamination control in microalgae cultures. This work evaluated the presence of bacterial contaminants in N. oleoabundans cultures through HTS and 16 S analysis and their susceptibility to six natural terpenes (α-pinene, ß-pinene, limonene, trans-cinnamaldehyde, linalool, and eugenol). The principal phyla identified were Proteobacteria, Bacteroidetes, and Actinobacteria, and based on these data, 89 bacterial isolates of seven genera were obtained (36 Aureimonas sp., 27 Microbacterium sp., 5 Pseudomonas sp., 9 Bacillus sp., 14 Shinella sp., 1 Brevundimonas sp., and 1 Exiguobacterium sp.) at 25ºC in the presence of light. It was possible to observe that Beta-pinene 50 mg L- 1 only inhibited Bacillus sp. In contrast, Alpha-pinene, Linalool, and Trans-cinnamaldehyde, at a concentration of 6.25 mg L- 1 efficiently inhibited most isolates. The inhibition percentages found were 79-99%.

Leukoreduction as a control measure in transfusion transmission of visceral leishmaniasis.

BACKGROUND: Asymptomatic visceral leishmaniasis (VL) infection is a risk for transfusion safety. Leukoreduction has been an alternative for the prevention of some blood-borne diseases, including VL. This study aimed to evaluate the role of leukoreduction of cellular blood components as a control measure for transfusional VL transmission. RESEARCH DESIGN AND METHODS: A total of 161 polytransfused patients with non-leukoreduced blood components (HNL), 95 polytransfused with leukoreduced blood components (LH), and 202 non-transfused (NT) from endemic regions for VL and with a similar epidemiological profile. The detection of antibodies against VL was performed by ELISA and the presence of the parasite was investigated by real-time PCR. Statistical significance was defined as p < .05. RESULTS: When comparing three groups, ELISA results were statistically significant (p = .0065). The residual analysis of ELISA showed statistically significant for the HNL group compared to the general group (p = .002; OR: 5.6; CI: 1.7-25.8), demonstrating that individuals who received non-leukoreduced transfusions are five times more likely to acquire Leishmania infantum infection than the general. DISCUSSION: Higher prevalence in the group with HNL and low prevalence in those who received LH, similar to NT patients, highlight the risk of transfusional VL transmission and reinforce the role of leukoreduction in its prevention.

Changes in cerebral autoregulation and vasoreactivity after surgical aortic valve replacement: a prospective study.

NEW FINDINGS: What is the central question of this study? How are dynamic cerebral autoregulation and brain vasoreactivity influenced by severe aortic stenosis and its surgical treatment? What are the main findings and their importance? Dynamic cerebral autoregulation is preserved in the long term in patients with severe aortic stenosis and does not change after surgical aortic valve replacement. However, carbon dioxide vasoreactivity is impaired in these patients. ABSTRACT: Surgical aortic valve replacement (SAVR) alters the natural course of severe aortic stenosis (AS). In this study, we aimed to determine the effects of the disease on dynamic cerebral autoregulation and vasoreactivity (VR) and to assess their changes after SAVR. We recruited 23 patients diagnosed with severe AS eligible for SAVR and 15 healthy matched controls. AS patients had lower mean VR to CO2 (P = 0.005) than controls, but dynamic cerebral autoregulation was preserved. Cerebral haemodynamics showed no significant change after SAVR. Patients with smaller baseline aortic valve areas presented with smaller low frequency phase changes after surgery (P = 0.016). Severe AS does not seem to impact dynamic cerebral autoregulation but does reduce VR to CO2 . SAVR does not alter cerebral autoregulation nor vasoreactivity.

Unraveling potential enzymes and their functional role in fine cocoa beans fermentation using temporal shotgun metagenomics.

Cocoa beans fermentation is a spontaneous process, essential for the generation of quality starting material for fine chocolate production. The understanding of this process has been studied by the application of high-throughput sequencing technologies, which grants a better assessment of the different microbial taxa and their genes involved in this microbial succession. The present study used shotgun metagenomics to determine the enzyme-coding genes of the microbiota found in two different groups of cocoa beans varieties during the fermentation process. The statistical evaluation of the most abundant genes in each group and time studied allowed us to identify the potential metabolic pathways involved in the success of the different microorganisms. The results showed that, albeit the distinction between the initial (0 h) microbiota of each varietal group was clear, throughout fermentation (24-144 h) this difference disappeared, indicating the existence of selection pressures. Changes in the microbiota enzyme-coding genes over time pointed to the distinct ordering of fermentation at 24-48 h (T1), 72-96 h (T2), and 120-144 h (T3). At T1, the significantly more abundant enzyme-coding genes were related to threonine metabolism and those genes related to the glycolytic pathway, explained by the abundance of sugars in the medium. At T2, the genes linked to the metabolism of ceramides and hopanoids lipids were clearly dominant, which are associated with the resistance of microbial species to extreme temperatures and pH values. In T3, genes linked to trehalose metabolism, related to the response to heat stress, dominated. The results obtained in this study provided insights into the potential functionality of microbial community succession correlated to gene function, which could improve cocoa processing practices to ensure the production of more stable quality end products.

Enhancing the Recovery of Bioactive Compounds of Soybean Fermented with Rhizopus oligosporus Using Supercritical CO2: Antioxidant, Anti-Inflammatory, and Oxidative Proprieties of the Resulting Extract.

The aim of the present study was to evaluate the use of supercritical CO2 combined with cosolvent for the recovery of bioactive compounds of soybean fermented with Rhizopus oligosporus NRRL 2710. Soxhlet extractions using seven different organic solvents (n-hexane, petroleum ether, ethyl acetate, acetone, ethanol, methanol, and water) were initially performed for comparative purposes. The extracts obtained were characterized by physicochemical, antioxidant, total phenolic, and oxidative proprieties. For the Soxhlet extractions, the highest and lowest yields obtained were 45.24% and 15.56%, using methanol and hexane, respectively. The extraction using supercritical CO2 combined with ethanol as a static modifier (scCO2 + EtOH) presented, at a high pressure (25 MPa) and temperature (80 °C), a phenolic compound content of 1391.9 µg GAE g-1 and scavenging of 0.17 g, reaching a 42.87% yield. The extracts obtained by sCO2 + EtOH were characterized by high contents of essential fatty acids (linoleic acid and oleic acid) and bioactive compounds (gallic acid, trans-cinnamic acid, daidzein, and genistein). These extracts also showed a great potential for inhibiting hyaluronidase enzymes (i.e., anti-inflammatory activity). Thermogravimetric analyses of the samples showed similar profiles, with oil degradation values in the range from 145 to 540 °C, indicating progressive oil decomposition with a mass loss ranging from 93 to 98.7%. In summary, this study demonstrated the flexibility of scCO2 + EtOH as a green technology that can be used to obtain high-value-added products from fermented soybean.

Capturing the Recognition Dynamics of para-Sulfonato-calix[4]arenes by Cytochrome c: Toward a Quantitative Free Energy Assessment.

Calix[n]arenes' selective recognition of protein surfaces covers a broad range of timely applications, from controlling protein assembly and crystallization to trapping partially disordered proteins. Here, the interaction of para-sulfonated calix-[4]-arenes with cytochrome c is investigated through all-atom, explicit water molecular dynamics simulations which allow characterization of two binding sites in quantitative agreement with experimental evidence. Free energy calculations based on the MM-PBSA and the attach-pull-release (APR) methods highlight key residues implicated in the recognition process and provide binding free energy results in quantitative agreement with isothermal titration calorimetry. Our study emphasizes the role of MD simulations to capture and describe the "walk" of sulfonated calix-[4]-arenes on the cytochrome c surface, with the arginine R13 as a pivotal interacting residue. Our MD investigation allows, through the quasi-harmonic multibasin (QHMB) method, probing an allosteric reinforcement of several per-residue interactions upon calixarene binding, which suggests a more complex mode of action of these supramolecular auxiliaries.

What Is Candida Doing in My Food? A Review and Safety Alert on Its Use as Starter Cultures in Fermented Foods.

The use of yeasts as starter cultures was boosted with the emergence of large-scale fermentations in the 20th century. Since then, Saccharomyces cerevisiae has been the most common and widely used microorganism in the food industry. However, Candida species have also been used as an adjuvant in cheese production or as starters for coffee, cocoa, vegetable, meat, beer, and wine fermentations. A thorough screening of candidate Candida is sometimes performed to obtain the best performing strains to enhance specific features. Some commonly selected species include C. pulcherrima (teleomorph Metschnikowia pulcherrima) (wine), C. parapsilosis (teleomorph Monilia parapsilosis) (coffee), C. famata (teleomorph Debaryomyces hansenii) (cheese), and C. zeylanoides (teleomorph Kurtzmaniella zeylanoides) and C. norvegensis (teleomorph Pichia norvegensis) (cocoa). These species are associated with the production of key metabolites (food aroma formation) and different enzymes. However, safety-associated selection criteria are often neglected. It is widely known that some Candida species are opportunistic human pathogens, with important clinical relevance. Here, the physiology and metabolism of Candida species are addressed, initially emphasizing their clinical aspects and potential pathogenicity. Then, Candida species used in food fermentations and their functional roles are reported. We recommended that Candida not be used as food cultures if safety assessments are not performed. Some safety features are highlighted to help researchers choose methods and selection criteria.

Fermented Soy Products and Their Potential Health Benefits: A Review.

In the growing search for therapeutic strategies, there is an interest in foods containing natural antioxidants and other bioactive compounds capable of preventing or reversing pathogenic processes associated with metabolic disease. Fermentation has been used as a potent way of improving the properties of soybean and their components. Microbial metabolism is responsible for producing the ß-glucosidase enzyme that converts glycosidic isoflavones into aglycones with higher biological activity in fermented soy products, in addition to several end-metabolites associated with human health development, including peptides, phenolic acids, fatty acids, vitamins, flavonoids, minerals, and organic acids. Thus, several products have emerged from soybean fermentation by fungi, bacteria, or a combination of both. This review covers the key biological characteristics of soy and fermented soy products, including natto, miso, tofu, douchi, sufu, cheonggukjang, doenjang, kanjang, meju, tempeh, thua-nao, kinema, hawaijar, and tungrymbai. The inclusion of these foods in the diet has been associated with the reduction of chronic diseases, with potential anticancer, anti-obesity, antidiabetic, anticholesterol, anti-inflammatory, and neuroprotective effects. These biological activities and the recently studied potential of fermented soybean molecules against SARS-CoV-2 are discussed. Finally, a patent landscape is presented to provide the state-of-the-art of the transfer of knowledge from the scientific sphere to the industrial application.

Could salt intake directly affect the cerebral microvasculature in hypertension?

OBJECTIVES: Excess dietary salt and chronic kidney disease (CKD) are acknowledged stroke risk factors. The development of small vessel disease, similarly affecting the cerebral and renal microvasculatures, may be an important mechanistic link underlying this interaction. Therefore, we aimed to evaluate if the dietary salt intake and markers of CKD (estimated glomerular filtration rate, albuminuria) relate to transcranial Doppler (TCD) markers of cerebral small vessel disease (CSVD) in hypertensive patients. MATERIALS AND METHODS: Fifty-six hypertensive patients (57% with diabetes) underwent TCD monitoring in the middle (MCA) and posterior (PCA) cerebral arteries for evaluating neurovascular coupling (NVC), dynamic cerebral autoregulation (dCA), and vasoreactivity to carbon dioxide (VRCO2). We investigated the relation between renal parameters and TCD studies using Pearson's correlation coefficient and linear regression analyses. RESULTS: There were no associations between dCA, VRCO2, NVC, and renal function tests. However, there was a negative association between the daily salt intake and the natural frequency during visual stimulation (r2=0.101, ß=-0.340, p=0.035), indicative of increased rigidity of the cerebral resistance vessels that react to cognitive activation. CONCLUSIONS: In this cross-sectional study, we found an association between excess dietary salt consumption and CSVD in hypertensive patients. Future research is needed to evaluate whether the natural frequency could be an early, non-invasive, surrogate marker for microvascular dysfunction in hypertension.

Bioprospecting lipid-producing microorganisms: From metagenomic-assisted isolation techniques to industrial application and innovations.

Traditionally, lipid-producing microorganisms have been obtained via conventional bioprospecting based on isolation and screening techniques, demanding time and effort. Thus, high-throughput sequencing combined with conventional microbiological approaches has emerged as an advanced and rapid strategy for recovering novel oleaginous microorganisms from target environments. This review highlights recent developments in lipid-producing microorganism bioprospecting, following (i) from traditional cultivation techniques to state-of-the-art metagenomics approaches; (ii) related topics on workflow, next-generation sequencing platforms, and knowledge bioinformatics; and (iii) biotechnological potential of the production of docosahexaenoic acid (DHA) by Aurantiochytrium limacinum, arachidonic acid (ARA) by Mortierella alpina and biodiesel by Rhodosporidium toruloides. These three species have been shown to be highly promising and studied in research articles, patents and commercialized products. Trends, innovations and future perspectives of these microorganisms are also addressed. Thus, these microbial lipids allow the development of food, feed and biofuels as alternative solutions to animal and vegetable oils.