Dietary Fiber Modulates the Release of Gut Bacterial Products Preventing Cognitive Decline in an Alzheimer's Mouse Model.

Fiber intake is associated with a lower risk for Alzheimer´s disease (AD) in older adults. Intake of plant-based diets rich in soluble fiber promotes the production of short-chain fatty acids (SCFAs: butyrate, acetate, propionate) by gut bacteria. Butyrate administration has antiinflammatory actions, but propionate promotes neuroinflammation. In AD patients, gut microbiota dysbiosis is a common feature even in the prodromal stages of the disease. It is unclear whether the neuroprotective effects of fiber intake rely on gut microbiota modifications and specific actions of SCFAs in brain cells. Here, we show that restoration of the gut microbiota dysbiosis through the intake of soluble fiber resulted in lower propionate and higher butyrate production, reduced astrocyte activation and improved cognitive function in 6-month-old male APP/PS1 mice. The neuroprotective effects were lost in antibiotic-treated mice. Moreover, propionate promoted higher glycolysis and mitochondrial respiration in astrocytes, while butyrate induced a more quiescent metabolism. Therefore, fiber intake neuroprotective action depends on the modulation of butyrate/propionate production by gut bacteria. Our data further support and provide a mechanism to explain the beneficial effects of dietary interventions rich in soluble fiber to prevent dementia and AD. Fiber intake restored the concentration of propionate and butyrate by modulating the composition of gut microbiota in male transgenic (Tg) mice with Alzheimer´s disease. Gut dysbiosis was associated with intestinal damage and high propionate levels in control diet fed-Tg mice. Fiber-rich diet restored intestinal integrity and promoted the abundance of butyrate-producing bacteria. Butyrate concentration was associated with better cognitive performance in fiber-fed Tg mice. A fiber-rich diet may prevent the development of a dysbiotic microbiome and the related cognitive dysfunction in people at risk of developing Alzheimer´s disease.

Severe SARS-CoV-2 Pneumonia and Pneumomediastinum/Pneumothorax: A Prospective Observational Study in an Intermediate Respiratory Care Unit.

INTRODUCTION: The occurrence of pneumomediastinum (PM) and/or pneumothorax (PTX) in patients with severe pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated. METHODS: This was a prospective observational study conducted in patients admitted to the intermediate respiratory care unit (IRCU) of a COVID-19 monographic hospital in Madrid (Spain) between December 14, 2020 and September 28, 2021. All patients had a diagnosis of severe SARS-CoV-2 pneumonia and required noninvasive respiratory support (NIRS): high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), and bilevel positive airway pressure (BiPAP). The incidences of PM and/or PTX, overall and by NIRS, and their impact on the probabilities of invasive mechanical ventilation (IMV) and death were studied. RESULTS: A total of 1306 patients were included. 4.3% (56/1306) developed PM/PTX, 3.8% (50/1306) PM, 1.6% (21/1306) PTX, and 1.1% (15/1306) PM + PTX. 16.1% (9/56) of patients with PM/PTX had HFNC alone, while 83.9% (47/56) had HFNC + CPAP/BiPAP. In comparison, 41.7% (521/1250) of patients without PM and PTX had HFNC alone (odds ratio [OR] 0.27; 95% confidence interval [95% CI] 0.13-0.55; p < .001), while 58.3% (729/1250) had HFNC + CPAP/BiPAP (OR 3.73; 95% CI 1.81-7.68; p < .001). The probability of needing IMV among patients with PM/PTX was 67.9% (36/53) (OR 7.46; 95% CI 4.12-13.50; p < .001), while it was 22.1% (262/1185) among patients without PM and PTX. Mortality among patients with PM/PTX was 33.9% (19/56) (OR 4.39; 95% CI 2.45-7.85; p < .001), while it was 10.5% (131/1250) among patients without PM and PTX. CONCLUSIONS: In patients admitted to the IRCU for severe SARS-CoV-2 pneumonia requiring NIRS, incidences of PM/PTX, PM, PTX, and PM + PTX were observed to be 4.3%, 3.8%, 1.6%, and 1.1%, respectively. Most patients with PM/PTX had HFNC + CPAP/BiPAP as the NIRS device, much more frequently than patients without PM and PTX. The probabilities of IMV and death among patients with PM/PTX were 64.3% and 33.9%, respectively, higher than those observed in patients without PM and PTX, which were 21.0% and 10.5%, respectively.

Interaction of chiral L-dialanine with Cu(100).

We report on the properties of the thin films of the short peptide L-dialanine grown on Cu(100) surfaces and compare them to those of L-alanine by using surface techniques like XPS, IRRAS and STM. The first dialanine monolayer, in contact with the metallic substrate, is found to consist of whole neutral molecules in the non-zwitterionic state forming a c(2 × 4) pattern with quasi-hexagonal symmetry. The peptide bond of dialanine is preserved in the adsorption state. The ordering of the L-dialanine overlayer is shown to replicate rearrangements of the atoms of the substrate around dislocations of the latter indicating a strong molecule-surface interaction. In the multilayer regime, molecules of the second and further layers are found to be in a zwitterionic state, readily desorbing even at room temperature. The first dialanine layer is tightly bound to the substrate, begins to desorb at temperatures higher than 390 K and cracks down at the surface, transforming into a new moiety, beyond 435 K.

Information Security and Privacy in Railway Transportation: A Systematic Review.

Intelligent transportation systems will play a key role in the smart cities of the future. In particular, railway transportation is gaining attention as a promising solution to cope with the mobility challenges in large urban areas. Thanks to the miniaturisation of sensors and the deployment of fast data networks, the railway industry is being augmented with contextual, real-time information that opens the door to novel and personalised services. Despite the benefits of this digitalisation, the high complexity of railway transportation entails a number of challenges, particularly from security and privacy perspectives. Since railway assets are attractive targets for terrorism, coping with strong security and privacy requirements such as cryptography and privacy-preserving methods is of utmost importance. This article provides a thorough systematic literature review on information security and privacy within railway transportation systems, following the well-known methodology proposed by vom Brocke et al. We sketch out the most relevant studies and outline the main focuses, challenges and solutions described in the literature, considering technical, societal, regulatory and ethical approaches. Additionally, we discuss the remaining open issues and suggest several research lines that will gain relevance in the years to come.

High rates of calcium-free diffusion in the cytosol of living cells.

Calcium (Ca2+) is a universal second messenger that participates in the regulation of innumerous physiological processes. The way in which local elevations of the cytosolic Ca2+ concentration spread in space and time is key for the versatility of the signals. Ca2+ diffusion in the cytosol is hindered by its interaction with proteins that act as buffers. Depending on the concentrations and the kinetics of the interactions, there is a large range of values at which Ca2+ diffusion can proceed. Having reliable estimates of this range, particularly of its highest end, which corresponds to the ions free diffusion, is key to understand how the signals propagate. In this work, we present the first experimental results with which the Ca2+-free diffusion coefficient is directly quantified in the cytosol of living cells. By means of fluorescence correlation spectroscopy experiments performed in Xenopus laevis oocytes and in cells of Saccharomyces cerevisiae, we show that the ions can freely diffuse in the cytosol at a higher rate than previously thought.

Scalable phylogenetic profiling using MinHash uncovers likely eukaryotic sexual reproduction genes.

Phylogenetic profiling is a computational method to predict genes involved in the same biological process by identifying protein families which tend to be jointly lost or retained across the tree of life. Phylogenetic profiling has customarily been more widely used with prokaryotes than eukaryotes, because the method is thought to require many diverse genomes. There are now many eukaryotic genomes available, but these are considerably larger, and typical phylogenetic profiling methods require at least quadratic time as a function of the number of genes. We introduce a fast, scalable phylogenetic profiling approach entitled HogProf, which leverages hierarchical orthologous groups for the construction of large profiles and locality-sensitive hashing for efficient retrieval of similar profiles. We show that the approach outperforms Enhanced Phylogenetic Tree, a phylogeny-based method, and use the tool to reconstruct networks and query for interactors of the kinetochore complex as well as conserved proteins involved in sexual reproduction: Hap2, Spo11 and Gex1. HogProf enables large-scale phylogenetic profiling across the three domains of life, and will be useful to predict biological pathways among the hundreds of thousands of eukaryotic species that will become available in the coming few years. HogProf is available at https://github.com/DessimozLab/HogProf.

Balance disorders as potential confounders associated with an increased risk of acute cerebrovascular accidents.

PURPOSE: There is a higher risk of stroke after suffering from balance disorders (BDs) such as vertigo or dizziness. The causal relationship remains unclear due to the limited scope of the existing studies and the high prevalence of cardiovascular risk factors (CVRFs) in BD patients. The objective of this study is to clarify the role that BDs seem to have in the development of acute cerebrovascular accidents (ACAs). METHODS: This is an observational prospective study. The CVRFs and demographic factors of a sample of our population were noted. Five clusters of patients were tracked over the course of 2 years to detect and diagnose BDs and ACAs. The causal relationships between the CVRFs, BDs and ACAs were analyzed in a univariate analysis. A logistic regression multivariant analysis was performed on those variables that reached statistical significance. RESULTS: The sample included 7886 participants and 31 ACAs were recorded. CVRFs that reached statistical significance included age ≥ 60, hypertension, diabetes mellitus, dyslipidemia, ischemic heart disease, atrial fibrillation and previous ACAs. The relationship between BDs and ACAs always reached statistical significance, regardless of how the BD variable was defined. Five different multivariate analyses were performed, but in none of them did the BD variables significantly reduce the deviance and thus, they were not taken into account when building the final model. CONCLUSION: This study shows that BDs are probably confounders that are closely linked to other CVRFs and they are also useful red flags to identify patients at a higher risk of suffering from ACAs.

Sensors for Context-Aware Smart Healthcare: A Security Perspective.

The advances in the miniaturisation of electronic devices and the deployment of cheaper and faster data networks have propelled environments augmented with contextual and real-time information, such as smart homes and smart cities. These context-aware environments have opened the door to numerous opportunities for providing added-value, accurate and personalised services to citizens. In particular, smart healthcare, regarded as the natural evolution of electronic health and mobile health, contributes to enhance medical services and people's welfare, while shortening waiting times and decreasing healthcare expenditure. However, the large number, variety and complexity of devices and systems involved in smart health systems involve a number of challenging considerations to be considered, particularly from security and privacy perspectives. To this aim, this article provides a thorough technical review on the deployment of secure smart health services, ranging from the very collection of sensors data (either related to the medical conditions of individuals or to their immediate context), the transmission of these data through wireless communication networks, to the final storage and analysis of such information in the appropriate health information systems. As a result, we provide practitioners with a comprehensive overview of the existing vulnerabilities and solutions in the technical side of smart healthcare.

Can news help measure economic sentiment? An application in COVID-19 times.

We construct a new newspaper-based sentiment indicator for Spain that allows to monitor economic activity in real-time. As opposed to survey-based confidence indicators that are released at the end of the month, our indicator can be constructed on a daily basis. We compare our index with the popular Economic Sentiment Indicator of the European Commission and show that ours performs significantly better in nowcasting the Spanish GDP. Moreover, it proves to be helpful to predict the current COVID-19 recession from an earlier date.

The balance between deterministic and stochastic processes in structuring lake bacterioplankton community over time.

One major goal in microbial ecology is to establish the importance of deterministic and stochastic processes for community assembly. This is relevant to explain and predict how diversity changes at different temporal scales. However, understanding of the relative quantitative contribution of these processes and particularly of how they may change over time is limited. Here, we assessed the importance of deterministic and stochastic processes based on the analysis of the bacterial microbiome in one alpine oligotrophic and in one subalpine mesotrophic lake, which were sampled over two consecutive years at different time scales. We found that in both lakes, homogeneous selection (i.e., a deterministic process) was the main assembly process at the annual scale and explained 66.7% of the bacterial community turnover, despite differences in diversity and temporal variability patterns between ecosystems. However, in the alpine lake, homogenizing dispersal (i.e., a stochastic process) was the most important assembly process at the short-term (daily and weekly) sampling scale and explained 55% of the community turnover. Alpha diversity differed between lakes, and seasonal stability of the bacterial community was more evident in the oligotrophic lake than in the mesotrophic one. Our results demonstrate how important forces that govern temporal changes in bacterial communities act at different time scales. Overall, our study validates on a quantitative basis, the importance and dominance of deterministic processes in structuring bacterial communities in freshwater environments over long time scales.

Genomic and Transcriptomic Basis of Hanseniaspora vineae's Impact on Flavor Diversity and Wine Quality.

Hanseniaspora is the main genus of the apiculate yeast group that represents approximately 70% of the grape-associated microflora. Hanseniaspora vineae is emerging as a promising species for quality wine production compared to other non-Saccharomyces species. Wines produced by H. vineae with Saccharomyces cerevisiae consistently exhibit more intense fruity flavors and complexity than wines produced by S. cerevisiae alone. In this work, genome sequencing, assembling, and phylogenetic analysis of two strains of H. vineae showed that it is a member of the Saccharomyces complex and it diverged before the whole-genome duplication (WGD) event from this clade. Specific flavor gene duplications and absences were identified in the H. vineae genome compared to 14 fully sequenced industrial S. cerevisiae genomes. The increased formation of 2-phenylethyl acetate and phenylpropanoids such as 2-phenylethyl and benzyl alcohols might be explained by gene duplications of H. vineae aromatic amino acid aminotransferases (ARO8 and ARO9) and phenylpyruvate decarboxylases (ARO10). Transcriptome and aroma profiles under fermentation conditions confirmed these genes were highly expressed at the beginning of stationary phase coupled to the production of their related compounds. The extremely high level of acetate esters produced by H. vineae compared to that by S. cerevisiae is consistent with the identification of six novel proteins with alcohol acetyltransferase (AATase) domains. The absence of the branched-chain amino acid transaminases (BAT2) and acyl coenzyme A (acyl-CoA)/ethanol O-acyltransferases (EEB1) genes correlates with H. vineae's reduced production of branched-chain higher alcohols, fatty acids, and ethyl esters, respectively. Our study provides sustenance for understanding and potentially utilizing genes that determine fermentation aromas.IMPORTANCE The huge diversity of non-Saccharomyces yeasts in grapes is dominated by the apiculate genus Hanseniaspora Two native strains of Hanseniaspora vineae applied to winemaking because of their high oenological potential in aroma and fermentation performance were selected to obtain high-quality genomes. Here, we present a phylogenetic analysis and the complete transcriptome and aroma metabolome of H. vineae during three fermentation steps. This species produced significantly richer flavor compound diversity than Saccharomyces, including benzenoids, phenylpropanoids, and acetate-derived compounds. The identification of six proteins, different from S. cerevisiae ATF, with diverse acetyltransferase domains in H. vineae offers a relevant source of native genetic variants for this enzymatic activity. The discovery of benzenoid synthesis capacity in H. vineae provides a new eukaryotic model to dilucidate an alternative pathway to that catalyzed by plants' phenylalanine lyases.

Morphological and morphometric variations of Dicrocoelium rileyi (Digenea: Dicrocoelidae) parasitizing Tadarida brasiliensis (Chiroptera: Molosiidae) in Mexico.

Fifty-five adult Dicrocoelium rileyi Macy, 1931 parasitizing Tadarida brasiliensis (Geoffroy, 1824) from Durango, Nuevo Leon, Puebla, Zacatecas and Mexico State were morphologically described and morphometrically analyzed. To evaluate the degree of variation among populations from the five localities, 27 morphometric measures of this species were transformed into an orthogonal factor by principal component analysis (PCA), and a posterior comparison among populations was performed using discriminant analysis of principal components (DAPC). Significant differences were observed with exceptions between the Puebla - Zacatecas and Nuevo Leon - Mexico State populations when forming three groups with an 88 % assignation. The Durango population was the most dissimilar population. These results show that the morphological traits of D. rileyi are variable among the populations in this study due to local intraspecific variation; however, some of the specimens present in the distinct localities may represent different species. Molecular analysis is necessary to accurately define whether the populations involved in our study constitute one or several species.

Subtercola vilae sp. nov., a novel actinobacterium from an extremely high-altitude cold volcano lake in Chile.

A novel actinobacterium, strain DB165T, was isolated from cold waters of Llullaillaco Volcano Lake (6170 m asl) in Chile. Phylogenetic analysis based on 16S rRNA gene sequences identified strain DB165T as belonging to the genus Subtercola in the family Microbacteriaceae, sharing 97.4% of sequence similarity with Subtercola frigoramans DSM 13057T, 96.7% with Subtercola lobariae DSM 103962T, and 96.1% with Subtercola boreus DSM 13056T. The cells were observed to be Gram-positive, form rods with irregular morphology, and to grow best at 10-15 °C, pH 7 and in the absence of NaCl. The cross-linkage between the amino acids in its peptidoglycan is type B2γ; 2,4-diaminobutyric acid is the diagnostic diamino acid; the major respiratory quinones are MK-9 and MK-10; and the polar lipids consist of phosphatidylglycerol, diphosphatidylglycerol, 5 glycolipids, 2 phospholipids and 5 additional polar lipids. The fatty acid profile of DB165T (5% >) contains iso-C14:0, iso-C16:0, anteiso-C15:0, anteiso-C17:0, and the dimethylacetal iso-C16:0 DMA. The genomic DNA G+C content of strain DB165T was determined to be 65 mol%. Based on the phylogenetic, phenotypic, and chemotaxonomic analyses presented in this study, strain DB165T (= DSM 105013T = JCM 32044T) represents a new species in the genus Subtercola, for which the name Subtercola vilae sp. nov. is proposed.

Genetic basis of cell-cell fusion mechanisms.

Cell-cell fusion in sexually reproducing organisms is a mechanism to merge gamete genomes and, in multicellular organisms, it is a strategy to sculpt organs, such as muscle, bone, and placenta. Moreover, this mechanism has been implicated in pathological conditions, such as infection and cancer. Studies of genetic model organisms have uncovered a unifying principle: cell fusion is a genetically programmed process. This process can be divided in three stages: competence (cell induction and differentiation); commitment (cell determination, migration, and adhesion); and cell fusion (membrane merging and cytoplasmic mixing). Recent work has led to the discovery of fusogens, which are cell fusion proteins that are necessary and sufficient to fuse cell membranes. Two unrelated families of fusogens have been discovered, one in mouse placenta and one in Caenorhabditis elegans (syncytins and F proteins, respectively). Current research aims to identify new fusogens and determine the mechanisms by which they merge membranes.

A white dwarf cooling age of 8 Gyr for NGC 6791 from physical separation processes.

NGC 6791 is a well studied open cluster that it is so close to us that can be imaged down to very faint luminosities. The main-sequence turn-off age ( approximately 8 Gyr) and the age derived from the termination of the white dwarf cooling sequence ( approximately 6 Gyr) are very different. One possible explanation is that as white dwarfs cool, one of the ashes of helium burning, (22)Ne, sinks in the deep interior of these stars. At lower temperatures, white dwarfs are expected to crystallize and phase separation of the main constituents of the core of a typical white dwarf ((12)C and (16)O) is expected to occur. This sequence of events is expected to introduce long delays in the cooling times, but has not hitherto been proven. Here we report that, as theoretically anticipated, physical separation processes occur in the cores of white dwarfs, resolving the age discrepancy for NGC 6791.

Surface-Guided Formation of an Organocobalt Complex.

Organocobalt complexes represent a versatile tool in organic synthesis as they are important intermediates in Pauson-Khand, Friedel-Crafts, and Nicholas reactions. Herein, a single-molecule-level investigation addressing the formation of an organocobalt complex at a solid-vacuum interface is reported. Deposition of 4,4'-(ethyne-1,2-diyl)dibenzonitrile and Co atoms on the Ag(111) surface followed by annealing resulted in genuine complexes in which single Co atoms laterally coordinated to two carbonitrile groups undergo organometallic bonding with the internal alkyne moiety of adjacent molecules. Alternative complexation scenarios involving fragmentation of the precursor were ruled out by complementary X-ray photoelectron spectroscopy. According to density functional theory analysis, the complexation with the alkyne moiety follows the Dewar-Chatt-Duncanson model for a two-electron-donor ligand where an alkyne-to-Co donation occurs together with a strong metal-to-alkyne back-donation.

Eisosomes are dynamic plasma membrane domains showing pil1-lsp1 heteroligomer binding equilibrium.

Eisosomes are plasma membrane domains concentrating lipids, transporters, and signaling molecules. In the budding yeast Saccharomyces cerevisiae, these domains are structured by scaffolds composed mainly by two cytoplasmic proteins Pil1 and Lsp1. Eisosomes are immobile domains, have relatively uniform size, and encompass thousands of units of the core proteins Pil1 and Lsp1. In this work we used fluorescence fluctuation analytical methods to determine the dynamics of eisosome core proteins at different subcellular locations. Using a combination of scanning techniques with autocorrelation analysis, we show that Pil1 and Lsp1 cytoplasmic pools freely diffuse whereas an eisosome-associated fraction of these proteins exhibits slow dynamics that fit with a binding-unbinding equilibrium. Number and brightness analysis shows that the eisosome-associated fraction is oligomeric, while cytoplasmic pools have lower aggregation states. Fluorescence lifetime imaging results indicate that Pil1 and Lsp1 directly interact in the cytoplasm and within the eisosomes. These results support a model where Pil1-Lsp1 heterodimers are the minimal eisosomes building blocks. Moreover, individual-eisosome fluorescence fluctuation analysis shows that eisosomes in the same cell are not equal domains: while roughly half of them are mostly static, the other half is actively exchanging core protein subunits.

Quantitation of yeast cell-cell fusion using multicolor flow cytometry.

Mating of haploid Saccharomyces cerevisiae cells of opposite sex provides a powerful model system to study the cell-cell fusion. However, a rapid and standardized method is much needed for quantitative assessment of fusion efficiency. The gold standard method relies on counting mating pairs in fluorescence microscopy images. This current method is limited by expectancy bias and it is time consuming, restricting the number of both cell-cell fusion events and strains that can be analyzed at once. Automatic approaches present a solution to these limitations. Here, we describe a novel flow cytometric approach that is able to quickly both identify mating pairs within a mixture of gametes and quantify cell fusion efficiency. This method is based on staining the cell wall of yeast populations with different Concanavalin A-fluorophore conjugates. The mating subpopulation is identified as the two-colored events set and fused and unfused mating pairs are subsequently discriminated by green fluorescent protein bimolecular complementation. A series of experiments was conducted to validate a simple and reliable protocol. Mating efficiency in each sample was determined by flow cytometry and compared with the one obtained with the current gold standard technique. The results show that mating pair counts using both methods produce indistinguishable outcomes and that the flow cytometry-based method provides quantitative relevant information in a short time, making possible to quickly analyze many different cell populations. In conclusion, our data show multicolor flow cytometry-based fusion quantitation to be a fast, robust, and reliable method to quantify the cell-cell fusion in yeast.

FigA, a putative homolog of low-affinity calcium system member Fig1 in Saccharomyces cerevisiae, is involved in growth and asexual and sexual development in Aspergillus nidulans.

Calcium-mediated signaling pathways are widely employed in eukaryotes and are implicated in the regulation of diverse biological processes. In Saccharomyces cerevisiae, at least two different calcium uptake systems have been identified: the high-affinity calcium influx system (HACS) and the low-affinity calcium influx system (LACS). Compared to the HACS, the LACS in fungi is not well known. In this study, FigA, a homolog of the LACS member Fig1 from S. cerevisiae, was functionally characterized in the filamentous fungus Aspergillus nidulans. Loss of figA resulted in retardant hyphal growth and a sharp reduction of conidial production. Most importantly, FigA is essential for the homothallic mating (self-fertilization) process; further, FigA is required for heterothallic mating (outcrossing) in the absence of HACS midA. Interestingly, in a figA deletion mutant, adding extracellular Ca(2+) rescued the hyphal growth defects but could not restore asexual and sexual reproduction. Furthermore, quantitative PCR results revealed that figA deletion sharply decreased the expression of brlA and nsdD, which are known as key regulators during asexual and sexual development, respectively. In addition, green fluorescent protein (GFP) tagging at the C terminus of FigA (FigA::GFP) showed that FigA localized to the center of the septum in mature hyphal cells, to the location between vesicles and metulae, and between the junctions of metulae and phialides in conidiophores. Thus, our findings suggest that FigA, apart from being a member of a calcium uptake system in A. nidulans, may play multiple unexplored roles during hyphal growth and asexual and sexual development.