Miracle-dz/UniFAR-FTUs huggingface dataset:
P300, Gray Matter Volume and Individual Characteristics Correlates in Healthy Elderly

We investigated whether P300-ERP and cognitive test performance differ for age, sex, and education in two groups of healthy elderly, and verified whether any correlations exist between P300 amplitude and latency and gray matter volume using whole brain voxel-by-voxel-based mapping, controlling for age, education, sex and Total Intracranial Volume (TIV). We used 32 channel electroencephalograms (EEG) to record the P300 responses and 3T Magnetic Resonance Imaging (MRI) to determine gray matter volume. We recruited 36 native-Dutch speaking healthy older subjects, equally divided in two sub-groups of 52–64 and 65–76 years old, administered a battery of cognitive tests and recorded their demographics, EEGs and task performance; additionally, 16 adults from the second sub-group underwent an MRI scan. We found significant differences between age groups in their cognitive tests performance, P300 amplitudes for the frontal and parietal electrodes for the most difficult task, and P300 latencies for frontal, central and parietal electrodes for all three tasks difficulty levels. Interesting, sex and education affected cognitive and P300 results. Higher education was related to higher accuracy, and P300 amplitudes and shorter latencies. Moreover, females exhibited higher P300 amplitudes and shorter latencies, and better cognitive tasks performance compared to males. Additionally, for the 16 adults underwent to MRI scan, we found positive correlations between P300 characteristics in frontal, central and parietal areas and gray matter volume, controlling for demographic variables and TIV, but also showing that age, sex, and education correlate with gray matter volume. These findings provide support that age, sex, and education affect an individual’s cognitive, neurophysiological and structural characteristics, and therefore motivate the need to further investigate these in relation to P300 responses and gray matter volume in healthy elderly.
Arabidopsis U2AF65 Regulates Flowering Time and the Growth of Pollen Tubes

During pre-mRNA splicing, U2 small nuclear ribonucleoprotein auxiliary factor 65 (U2AF65) interacts with U2AF35 and splicing factor 1 (SF1), allowing for the recognition of the 3′-splice site by the ternary complex. The functional characterization of U2AF65 homologs has not been performed in Arabidopsis thaliana yet. Here, we show that normal plant development, including floral transition, and male gametophyte development, requires two Arabidopsis U2AF65 isoforms (AtU2AF65a and AtU2AF65b). Loss-of-function mutants of these two isoforms displayed opposite flowering phenotypes: atu2af65a mutants showed late flowering, whereas atu2af65b mutants were characterized by slightly early flowering, as compared to that in the wild-type (Col-0) plants. These abnormal flowering phenotypes were well-correlated with the expression patterns of the flowering time genes such as FLOWERING LOCUS C (FLC) and FLOWERING LOCUS T (FT). However, the two atu2af65 mutants did not display any morphological abnormalities or alterations in abiotic stress tests. Double mutation of the AtU2AF65a and AtU2AF65b genes resulted in non-viable seeds due to defective male gametophyte. In vitro pollen germination test revealed that mutations in both AtU2AF65a and AtU2AF65b genes significantly impaired pollen tube growth. Collectively, our findings suggest that two protein isoforms of AtU2AF65 are differentially involved in regulating flowering time and display a redundant role in pollen tube growth.
Understanding Ligand Binding to G-Protein Coupled Receptors Using Multiscale Simulations

Human G-protein coupled receptors (GPCRs) convey a wide variety of extracellular signals inside the cell and they are one of the main targets for pharmaceutical intervention. Rational drug design requires structural information on these receptors; however, the number of experimental structures is scarce. This gap can be filled by computational models, based on homology modeling and docking techniques. Nonetheless, the low sequence identity across GPCRs and the chemical diversity of their ligands may limit the quality of these models and hence refinement using molecular dynamics simulations is recommended. This is the case for olfactory and bitter taste receptors, which constitute the first and third largest GPCR groups and show sequence identities with the available GPCR templates below 20%. We have developed a molecular dynamics approach, based on the combination of molecular mechanics and coarse grained (MM/CG), tailored to study ligand binding in GPCRs. This approach has been applied so far to bitter taste receptor complexes, showing significant predictive power. The protein/ligand interactions observed in the simulations were consistent with extensive mutagenesis and functional data. Moreover, the simulations predicted several binding residues not previously tested, which were subsequently verified by carrying out additional experiments. Comparison of the simulations of two bitter taste receptors with different ligand selectivity also provided some insights into the binding determinants of bitter taste receptors. Although the MM/CG approach has been applied so far to a limited number of GPCR/ligand complexes, the excellent agreement of the computational models with the mutagenesis and functional data supports the applicability of this method to other GPCRs for which experimental structures are missing. This is particularly important for the challenging case of GPCRs with low sequence identity with available templates, for which molecular docking shows limited predictive power.
Comparative Analysis of the Two Acinetobacter baumannii Multilocus Sequence Typing (MLST) Schemes

Acinetobacter species assigned to the Acinetobacter calcoaceticus-baumannii (Acb) complex, are Gram-negative bacteria responsible for a large number of human infections. The population structure of Acb has been studied using two 7-gene MLST schemes, introduced by Bartual and coworkers (Oxford scheme) and by Diancourt and coworkers (Pasteur scheme). The schemes have three genes in common but underlie two coexisting nomenclatures of sequence types and clonal complexes, which complicates communication on A. baumannii genotypes. The aim of this study was to compare the characteristics of the two schemes to make a recommendation about their usage. Using genome sequences of 730 strains of the Acb complex, we evaluated the phylogenetic congruence of MLST schemes, the correspondence between sequence types, their discriminative power and genotyping reliability from genomic sequences. In silico ST re-assignments highlighted the presence of a second copy of the Oxford gdhB locus, present in 553/730 genomes that has led to the creation of artefactual profiles and STs. The reliability of the two MLST schemes was tested statistically comparing MLST-based phylogenies to two reference phylogenies (core-genome genes and genome-wide SNPs) using topology-based and likelihood-based tests. Additionally, each MLST gene fragment was evaluated by correlating the pairwise nucleotide distances between each pair of genomes calculated on the core-genome and on each single gene fragment. The Pasteur scheme appears to be less discriminant among closely related isolates, but less affected by homologous recombination and more appropriate for precise strain classification in clonal groups, which within this scheme are more often correctly monophyletic. Statistical tests evaluate the tree deriving from the Oxford scheme as more similar to the reference genome trees. Our results, together with previous work, indicate that the Oxford scheme has important issues: gdhB paralogy, recombination, primers sequences, position of the genes on the genome. While there is no complete agreement in all analyses, when considered as a whole the above results indicate that the Pasteur scheme is more appropriate for population biology and epidemiological studies of A. baumannii and related species and we propose that it should be the scheme of choice during the transition toward, and in parallel with, core genome MLST.
Hypsodont Crowns as Additional Roots: A New Explanation for Hypsodonty

The hypsodont crown of Equus and of other hypsodont ungulates has two functions: It is extra crown in the alveolus which erupts and becomes a functional crown that enables the horse to live longer and feed on abrasive foods and the grit. The second functional aspect is that the crown, while it is in the alveolus, acts as a root to support the high stresses during mastication. In general, roots do not increase is size during the evolution when the tooth crown increases. Delayed development of the true roots is a heterochrony phenomenon and it is possibly dynamically interactive with the forces applied on the crown. Thus, when the crown is worn a lot as in old age, the mastication forces acting on it are very strong. This is an interesting phenomenon and reinforces our hypothesis of the second functional difference that the young tooth’s crown embedded in the alveolus acts as a supporting root. The Equus hypsodont tooth has been represented by a class I lever. That is, the fulcrum is in the middle: the effort is applied on one side of the fulcrum and the resistance (or load) on the other side, for example, as in a crowbar. As an individual Equus ages, the alveolar tooth length decreases. The data display an exponential increase in force generated as tooth length decreases. The elongation and closure of the root is delayed until the crown is almost entirely worn. When the crown is worn, the mastication forces acting on it are very strong. This is an interesting phenomenon and reinforces our hypothesis that the young tooth’s crown embedded in the alveolus acts as a supporting root. This discovery is based in the observation that fossil ungulates most commonly die at an early age leaving a substantial amount of crown unused. The unused crown is not likely a reserve of tooth crown for a season of hardship because it is rare to find examples of such hardship in the fossil record.
The FDA “Black Box” Warning on Antidepressant Suicide Risk in Young Adults: More Harm Than Benefits?

The decision made in the year 2004 by the U.S. Food and Drug Administration (FDA) to require a boxed warning on antidepressants regarding the risk of suicidality in young adults still represents a matter of controversy. The FDA warning was grounded on industry-sponsored trials carried one decade ago or earlier. However, within the past decade, an increasing number of reports have questioned the actual validity of the FDA warning, especially considering a decline in the prescription of the antidepressant drugs associated with an increase in the rate of suicidal events among people with severe depression. The present report provides an overview of the FDA black box warning, also documenting two Major Depressive Disorder patients whose refusal to undergo a pharmacological antidepressant treatment possibly led to an increased risk for suicidal behaviors. The concerns raised by the FDA black box warning need to be considered in real-world clinical practice, stating the associated clinical and public health implications.
Abnormal proactive and reactive cognitive control during conflict processing in major depression.

According to the Dual Mechanisms of Control framework, cognitive control consists of two complementary components: proactive control refers to anticipatory maintenance of goal-relevant information, whereas reactive control acts as a correction mechanism that is activated when a conflict occurs. Possibly, the well-known diminished inhibitory control in response to negative stimuli in Major Depressive Disorder (MDD) patients stems from a breakdown in proactive control, and/or anomalies in reactive cognitive control. In our study, MDD patients specifically showed increased response latencies when actively inhibiting a dominant response to a sad compared with a happy face. This condition was associated with a longer duration of a dominant ERP topography (800-900 ms poststimulus onset) and a stronger activity in the bilateral dorsal anterior cingulate cortex, reflecting abnormal reactive control when inhibiting attention to a negative stimulus. Moreover, MDD patients showed abnormalities in proactive cognitive control when preparing for the upcoming imperative stimulus (abnormal modulation of the contingent negative variation component), accompanied by more activity in brain regions belonging to the default mode network. All together, deficits to inhibit attention to negative information in MDD might originate from an abnormal use of both proactive resources and reactive control processes.
Review of Different Sequence Motif Finding Algorithms

The DNA motif discovery is a primary step in many systems for studying gene function. Motif discovery plays a vital role in identification of Transcription Factor Binding Sites (TFBSs) that help in learning the mechanisms for regulation of gene expression. Over the past decades, different algorithms were used to design fast and accurate motif discovery tools. These algorithms are generally classified into consensus or probabilistic approaches that many of them are time-consuming and easily trapped in a local optimum. Nature-inspired algorithms and many of combinatorial algorithms are recently proposed to overcome these problems. This paper presents a general classification of motif discovery algorithms with new sub-categories that facilitate building a successful motif discovery algorithm. It also presents a summary of comparison between them.
Acoustic resonators for the reduction of sound radiation and transmission

Noise is a frequently encountered problem in modern society. One of the environments where the presence of noise causes a deterioration in people’s comfort is in aircraft cabins. For modern aircraft flying at cruise conditions, the main sound source is the turbulent boundary layer around the fuselage. Especially in the mid and high frequency range (500-2000 Hz), this source significantly contributes to the sound levels in the aircraft cabin. Passive noise reduction methods can provide a suitable solution to many noise problems in this frequency range. In the present study, a new passive noise reduction method is presented, known as tube resonators. Tube resonators are well-known for their application for sound absorption. However, in the present work, this type of resonator is applied for the reduction of sound radiation and sound transmission. The aim of this work is to investigate the applicability of this new method and to develop and validate efficient models for the prediction of sound radiation by and sound transmission through panels with tube resonators. For a proper understanding of the influences of the different phenomena, different models and experiments are presented in order of increasing complexity.
H2 formation and excitation in the Stephan's Quintet galaxy-wide collision

Context. The Spitzer Space Telescope has detected a powerful (L_(H_2) ~ 10^(41) erg s^(-1)) mid-infrared H_2 emission towards the galaxy-wide collision in the Stephan's Quintet (henceforth SQ) galaxy group. This discovery was followed by the detection of more distant H_2-luminous extragalactic sources, with almost no spectroscopic signatures of star formation. These observations place molecular gas in a new context where one has to describe its role as a cooling agent of energetic phases of galaxy evolution. Aims. The SQ postshock medium is observed to be multiphase, with H_2 gas coexisting with a hot (~5 × 10^6 K), X-ray emitting plasma. The surface brightness of H_2 lines exceeds that of the X-rays and the 0-0 S(1)H_2 linewidth is ~900 km s^(-1), of the order of the collision velocity. These observations raise three questions we propose to answer: (i) why is H_2 present in the postshock gas? (ii) How can we account for the H_2 excitation? (iii) Why is H_2 a dominant coolant? Methods. We consider the collision of two flows of multiphase dusty gas. Our model quantifies the gas cooling, dust destruction, H_2 formation and excitation in the postshock medium. Results. (i) The shock velocity, the post-shock temperature and the gas cooling timescale depend on the preshock gas density. The collision velocity is the shock velocity in the low density volume-filling intercloud gas. This produces a ~5 × 10^6 K, dust-free, X-ray emitting plasma. The shock velocity is lower in clouds. We show that gas heated to temperatures of less than 10^6 K cools, keeps its dust content and becomes H_2 within the SQ collision age (~5 × 10^6 years). (ii) Since the bulk kinetic energy of the H_2 gas is the dominant energy reservoir, we consider that the H_2 emission is powered by the dissipation of kinetic turbulent energy. We model this dissipation with non-dissociative MHD shocks and show that the H_2 excitation can be reproduced by a combination of low velocities shocks (5-20 km s^(-1)) within dense (n_H > 10^3 cm^(-3)) H_2 gas. (iii) An efficient transfer of the bulk kinetic energy to turbulent motion of much lower velocities within molecular gas is required to make H_2 a dominant coolant of the postshock gas. We argue that this transfer is mediated by the dynamic interaction between gas phases and the thermal instability of the cooling gas. We quantify the mass and energy cycling between gas phases required to balance the dissipation of energy through the H_2 emission lines. Conclusions. This study provides a physical framework to interpret H_2 emission from H_2-luminous galaxies. It highlights the role that H_2 formation and cooling play in dissipating mechanical energy released in galaxy collisions. This physical framework is of general relevance for the interpretation of observational signatures, in particular H_2 emission, of mechanical energy dissipation in multiphase gas.
Expression Patterns for TETs, LGR5 and BMI1 in Cancer Stem-like Cells Isolated from Human Colon Cancer

Background: Colon tumor is generated and maintained by a small subset of chemo-resistant cancer cells known as Cancer Stem-like Cells (CSCs) that are able to self-renew and differentiate into various cell types within the cancer milieu. CSCs are identified through expression of CD133 that is the most important surface marker of these cells. Epithelial Cell Adhesion Molecule (EpCAM) is another colon CSCs marker. Other markers that are probably involved in colon tumorigenesis are Leucine-rich repeat-containing G-protein-coupled Receptor 5 (LGR5), B cell-specific Moloney murine leukemia virus insertion site 1 (BMI1) and Ten-Eleven Translocations (TETs). Methods: Here, mRNA expression rates of LGR5, BMI1 and TETs were surveyed by real-time PCR. After collection and digestion, colon samples were used to isolate CD133 and EpCAM positive CSCs through evaluation of AC133 EpCAM by Magnetic Activated Cell Sorting (MACS) and flow cytometry. Real-time PCR was carried out for assessing expressions of LGR5, BMI1 and TETs. Results: High expressions for LGR5, BMI1, TET1 and TET2 in the CD133 and EpCAM positive CSCs (p≤0.05 vs. non-CSCs) were found. TET3, however, showed no significant changes for mRNA expression in the CSCs. Conclusion: In conclusion, high mRNA expressions for LGR5, BMI1, TET1 and TET2 in the CD133 and EpCAM positive CSCs may be a useful criterion for better identification of the cells involved in colon cancer in order to specify therapeutic targets against this type of cancer.
Composition and Activity of an Autotrophic Fe(II)-Oxidizing, Nitrate-Reducing Enrichment Culture

ABSTRACT 16S rRNA gene libraries from the lithoautotrophic Fe(II)-oxidizing, nitrate-reducing enrichment culture described by Straub et al. (K. L. Straub, M. Benz, B. Schink, and F. Widdel, Appl. Environ. Microbiol. 62:1458-1460, 1996) were dominated by a phylotype related (95% 16S rRNA gene homology) to the autotrophic Fe(II) oxidizer Sideroxydans lithotrophicus. The libraries also contained phylotypes related to known heterotrophic nitrate reducers Comamonas badia, Parvibaculum lavamentivorans, and Rhodanobacter thiooxidans. The three heterotrophs were isolated and found to be capable of only partial (12 to 24%) Fe(II) oxidation, suggesting that the Sideroxydans species has primary responsibility for Fe(II) oxidation in the enrichment culture.
The Association of Intracranial Pressure Monitoring and Mortality: A Propensity Score-Matched Cohort of Isolated Severe Blunt Traumatic Brain Injury

Background: Intracranial pressure (ICP) monitoring in traumatic brain injury (TBI) is common. Yet, its efficacy varies between studies, and the actual effect on the outcome is debated. This study investigates the association of ICP monitoring and clinical outcome in patients with an isolated severe blunt TBI. Patients and Methods: Patients were recruited from the American College of Surgeons-Trauma Quality Improvement Program database during 2014. Inclusion criteria were limited to adult patients (≥18 years) who had a sustained isolated severe intracranial injury (Abbreviated Injury Scale [AIS] head of ≥3 and Glasgow Coma Scale [GCS] of ≤8) following blunt trauma to the head. Patients with AIS score >0 for any extracranial body area were excluded. Patients' demographics, injury characteristics, interventions, and outcomes were collected for analysis. Patients receiving ICP monitoring were matched in a 1:1 ratio with controls who were not ICP monitored using propensity score matching. Results: A total of 3289 patients met inclusion criteria. Of these, 601 (18.3%) were ICP monitored. After propensity score matching, 557 pairs were available for analysis with a mean age of 44 (standard deviation 18) years and 80.2% of them were male. Median GCS on admission was 4[3,7], and a third of patients required neurosurgical intervention. There were no statistical differences in any variables included in the analysis between the ICP-monitored group and their matched counterparts. ICP-monitored patients required significantly longer intensive care unit and hospital length of stay and had an increased mortality risk with odds ratio of 1.6 (95% confidence interval: 1.1–2.5, P = 0.038). Conclusion: ICP monitoring is associated with increased in-hospital mortality in patients with an isolated severe TBI. Further investigation into which patients may benefit from this intervention is required.
Subcortical Glutamate Mediates the Reduction of Short-Range Functional Connectivity with Age in a Developmental Cohort

Marked changes in brain physiology and structure take place between childhood and adulthood, including changes in functional connectivity and changes in the balance between main excitatory and inhibitory neurotransmitters glutamate (Glu) and GABA. The balance of these neurotransmitters is thought to underlie neural activity in general and functional connectivity networks in particular, but so far no studies have investigated the relationship between human development related differences in these neurotransmitters and concomitant changes in functional connectivity. GABA+/H2O and Glu/H2O levels were acquired in a group of healthy children, adolescents, and adults in a subcortical (basal ganglia) region, as well as in a frontal region in adolescents and adults. Our results showed higher GABA+/Glu with age in both the subcortical and the frontal voxel, which were differentially associated with significantly lower Glu/H2O with age in the subcortical voxel and by significantly higher GABA+/H2O with age in the frontal voxel. Using a seed-to-voxel analysis, we were further able to show that functional connectivity between the putamen (seed) and other subcortical structures was lower with age. Lower subcortical Glu/H2O with age mediated the lower connectivity in the dorsal putamen. Based on these results, and the potential role of Glu in synaptic pruning, we suggest that lower Glu mediates a reduction of local connectivity during human development.