Miracle-dz/UniFAR-FTUs huggingface dataset:
The Lbx1 lineage differentially contributes to inhibitory cell types of the dorsal cochlear nucleus, a cerebellum‐like structure, and the cerebellum

The dorsal cochlear nucleus (DCN) is a mammalian‐specific nucleus of the auditory system. Anatomically, it is classified as a cerebellum‐like structure. These structures are proposed to share genetic programs with the cerebellum. Previous analyses demonstrated that inhibitory serial sister cell types (SCTs) of the DCN and cerebellum are derived from the pancreatic transcription factor 1a (Ptf1a) lineage. Postmitotic neurons of the Ptf1a lineage often express the transcription factor Ladybird homeobox protein homolog 1 (Lbx1) which is involved in neuronal cell fate determination. Lbx1 is therefore an attractive candidate for a further component of the genetic program shared between the DCN and cerebellum. Here, we used cell‐type specific marker analysis in combination with an Lbx1 reporter mouse line to analyze in both tissues which cell types of the Ptf1a lineage express Lbx1. In the DCN, stellate cells and Purkinje‐like cartwheel cells were part of the Lbx1 lineage and Golgi cells were not, as determined by cell counts. In contrast, in the cerebellum, stellate cells and Golgi cells were part of the Lbx1 lineage and Purkinje cells were not. Hence, two out of three phenotypically similar cell types differed with respect to their Lbx1 expression. Our study demonstrates that Lbx1 is differentially recruited to the developmental genetic program of inhibitory neurons both within a given tissue and between the DCN and cerebellum. The differential expression of Lbx1 within the DCN and the cerebellum might contribute to the genetic individuation of the inhibitory SCTs to adapt to circuit specific tasks.
Cell Dimensions and Composition of Nanocrystalline Calcium Silicate Hydrate Solid Solutions. Part 2: X‐Ray and Thermogravimetry Study

X-ray diffraction and thermogravimetry have been used to analyze the limits of incorporation of Ca in a series of mechanochemically synthesized, nanocrystalline calcium silicate hydrate (C–S–H) phases. Results based on bulk weight loss and Rietveld refinements show higher C/S ratios than those corrected additionally for X-ray-silent CaCO3 and Ca(OH)2. A pure C–S–H phase exists over the C/S range 2/3–5/4, with two ordered end members. The structure of C–S–H phases within the interval 2/3–5/4 may well be described by the so-called defect-tobermorite model. At C/S=2/3, the C–S–H consists of 14 A tobermorite slabs linked via H-bonds without interlayer Ca, resulting in the formula Ca4[H2Si3O9]2·xH2O, where x=4. After heating up to 1000°C, X-ray diffraction has shown that even samples with a low Ca content (Ca/Si <2/3) contain solely the calcium silicate wollastonite. This supports the idea of a slightly defective, unbranched single chain silicate anion. Increasing the C/S ratio leads to increased disorder due to the competitive omission of bridging tetrahedra and the incorporation of Ca into the interlayer in samples with 2/3 < C/S <5/4. The Ca-rich end member with C/S=5/4 exhibits structural features of a tobermorite-based dimer: {Ca4[HSi2O7]2} . Ca . xH2O, where x=4. The observed change in the d-value of the basal reflection upon X-ray irradiation further supports the proposed model, relating the observed shrinkage with the loss of H2O molecules from the interlayer, where they coordinate calcium.
Significance of expression of tumor-associated microRNA-21 and -375 for predicting the course of cancer of oral cavity.

AIM To investigate the features of expression of miRNA-21 and miRNA-375 in tumor cells of patients with cancer of oral cavity (COC) and to determine the possibility of their use to predict the aggressiveness of COC course. MATERIALS AND METHODS The work is based on the results of examination and treatment of 50 patients with stage II-IV COC. miRNA expression in tumor cells was analyzed by real time reverse transcription polymerase chain reaction. RESULTS High levels of miRNA-21 expression (> 0.26 a.u.) and miRNA-375 (> 0.36 a.u.) were determined in 72.0% and 63.0% of cases. We revealed a tendency to decreased miRNA-21 expression and increased miRNA-375 expression in tumors of patients with recurrence-free survival less than 12 months and the presence of metastatic lesions in regional lymph nodes. In patients with COC of low differentiation grade, the level of miRNA-21 was 2.0 times lower compared with tumors of moderate differentiation grade (p < 0.05), while the expression of miRNA-375, on the contrary, was higher in tumors of low differentiation grade. A decreased expression of miRNA-21 (< 0.26 a.u.) against the background of decreased levels of miRNA-375 (< 0.36 a.u.) in tumor cells was associated with worse recurrence-free survival. CONCLUSIONS The obtained results indicate the relation between the main clinical and pathological characteristics of patients with COC and the levels of miRNA-21 and -375 expression in tumor tissue, which indicates the involvement of these miRNAs in the formation of COC malignancy evidencing on their potential usefulness as additional prognostic markers.
The enigmatic biology of rickettsiae: recent advances, open questions and outlook

ABSTRACT Rickettsiae are obligate intracellular bacteria that can cause life-threatening illnesses and are among the oldest known vector-borne pathogens. Members of this genus are extraordinarily diverse and exhibit a broad host range. To establish intracellular infection, Rickettsia species undergo complex, multistep life cycles that are encoded by heavily streamlined genomes. As a result of reductive genome evolution, rickettsiae are exquisitely tailored to their host cell environment but cannot survive extracellularly. This host-cell dependence makes for a compelling system to uncover novel host–pathogen biology, but it has also hindered experimental progress. Consequently, the molecular details of rickettsial biology and pathogenesis remain poorly understood. With recent advances in molecular biology and genetics, the field is poised to start unraveling the molecular mechanisms of these host–pathogen interactions. Here, we review recent discoveries that have shed light on key aspects of rickettsial biology. These studies have revealed that rickettsiae subvert host cells using mechanisms that are distinct from other better-studied pathogens, underscoring the great potential of the Rickettsia genus for revealing novel biology. We also highlight several open questions as promising areas for future study and discuss the path toward solving the fundamental mysteries of this neglected and emerging human pathogen.
The effect of needle and syringe program and opioid agonist therapy on the risk of HIV, hepatitis B and C virus infection for people who inject drugs in Amsterdam, the Netherlands: findings from an emulated target trial.

BACKGROUND AND AIMS Major declines in HIV and hepatitis C and B virus (HCV/HBV) incidence among people who inject drugs (PWID) have been attributed to early implementation of harm-reduction programs (HRP) in the Netherlands but alternative factors such as selective mortality and demographic and drug markets shifts over time likely contributed to observed incidence declines. We quantified and tested the effect of HRP participation on risk of these infections among PWID in Amsterdam, the Netherlands. DESIGN We emulated the design of a hypothetical, ideal randomized trial using observational data from the Amsterdam Cohort Studies (1985-2014). SETTING Amsterdam, the Netherlands PARTICIPANTS: We included PWID who ever used opioids, had a recent history of injecting drug use (IDU) and tested negative for HIV, HCV, or HBV. Of 983 participants, 640, 137 and 308 were included for the HIV, HCV and HBV analyses and 59, 45 and 49 seroconversions were observed, respectively. INTERVENTIONS Intervention arms were: complete HRP participation (≥60 mg/day methadone and 100% needle and syringe program (NSP) coverage, or any methadone dose if no recent injection drug use) versus no HRP and partial HRP participation combined (<60 methadone mg/day and/or <100% NSP coverage). MEASUREMENTS Separately for each infection, we estimated the hazard ratios (HR) comparing HRP arms using marginal structural models. FINDINGS Compared with no/partial HRP participation, complete HRP participation led to lower risk of HIV (HR=0.54, 95%CI:0.27-1.08), HCV (HR=0.16, 95%CI:0.06-0.40) and HBV (HR=0.28, 95%CI:0.13-0.61) acquisition. CONCLUSIONS Complete participation in harm reduction programs appears to have led to substantial decreases in HIV and hepatitis C and B virus acquisition risk among people who inject drugs in the Netherlands. FUNDING AidsFonds (Project number 29703), National Institute for Public Health and the Environment (the Netherlands), and Boston University/Brown CFAR P30 AI042853 (USA).
On the stoichiometry of the semiconductor pyrite (FeS2)

Abstract The compound semiconductor pyrite (FeS2) has recently attracted considerable attention as a possible absorber material for thin-film solar cells. In the literature, a controversy exists on the degree of its non-stoichiometry. In the present paper an analysis of the literature concerning this question is given. In spite of many reports on significant deviations from the ideal stoichiometry, no reliable proof exists that pyrite has an existence range which exceeds compositional variations of the order of 1 at %. To support this result, a theoretical estimation of the vacancy formation energy in pyrite has been performed. Based on the macroscopic cavity model of van Vechten and Phillips the vacancy formation energies E V(S) = 1·66 eV of a sulphur vacancy and E V(Fe)=2·18 eV of an iron vacancy were calculated. The formation energy of a complete Schottky defect E V(Fe + 2S) = 5·50 eV is in good agreement with a second value E V(Fe + 2S) = 5·80 eV, which was derived from Kroger's rule: E V≈0·5Hsub, whe.
LAMB1 Is Related to the T Stage and Indicates Poor Prognosis in Gastric Cancer

Background and Objective: Gastric cancer (GC) is a common tumor malignancy with high incidence and poor prognosis. Laminin is an indispensable component of basement membrane and extracellular matrix, which is responsible for bridging the internal and external environment of cells and transmitting signals. This study mainly explored the association of the LAMB1 expression with clinicopathological characteristics and prognosis in gastric cancer. Methods: The expression data and clinical information of gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG). And we analyzed the relationship between LAMB1 expression and clinical characteristics through R. CIBERSORTx was used to calculate the absolute score of immune cells in gastric tumor tissues. Then COX proportional hazard models and Kaplan-Meier curves were performed to evaluate the role of LAMB1 and its influence on prognosis in gastric cancer patients. Finally, GO and KEGG analysis were applied for LAMB1-related genes in gastric cancer, and PPI network was constructed in Cytoscape software. Results: In the TCGA cohort, patients with gastric cancer frequently generated LAMB1 gene copy number variation, but had little effect on mRNA expression. Both in the TCGA and ACRG cohorts, the mRNA expression of LAMB1 in gastric cancer tissues was higher than it in normal tissues. All patients were divided into high expression group and low expression group according to the median expression level of LAMB1. The elevated expression group obviously had more advanced cases and higher infiltration levels of M2 macrophages. COX proportional hazard models and Kaplan-Meier curves revealed that patients with enhanced expression of LAMB1 have a worse prognosis. GO/KEGG analysis showed that LAMB1-related genes were enriched in PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, etc. Conclusions: The high expression of LAMB1 in gastric cancer is related to the poor prognosis of patients, and it may be related to microenvironmental changes in tumors.
Functional Anatomy of the Trimer Apex Reveals Key Hydrophobic Constraints That Maintain the HIV-1 Envelope Spike in a Closed State

Elucidating the structure and function of the HIV-1 outer envelope proteins is critical for the design of an effective vaccine. Despite the availability of many high-resolution structures, key functional correlates in the envelope trimer remain undefined. ABSTRACT The human immunodeficiency virus type 1 (HIV-1) envelope trimer maintains a closed, metastable configuration to protect vulnerable epitopes from neutralizing antibodies. Here, we identify key hydrophobic constraints at the trimer apex that function as global stabilizers of the HIV-1 envelope spike configuration. Mutation of individual residues within four hydrophobic clusters that fasten together the V1V2, V3, and C4 domains at the apex of gp120 dramatically increases HIV-1 sensitivity to weak and restricted neutralizing antibodies targeting epitopes that are largely concealed in the prefusion Env spike, consistent with the adoption of a partially open trimer configuration. Conversely, the same mutations decrease the sensitivity to broad and potent neutralizing antibodies that preferentially recognize the closed trimer. Sera from chronically HIV-infected patients neutralize open mutants with enhanced potency, compared to the wild-type virus, suggesting that a large fraction of host-generated antibodies target concealed epitopes. The identification of structural constraints that maintain the HIV-1 envelope in an antibody-protected state may inform the design of a protective vaccine. IMPORTANCE Elucidating the structure and function of the HIV-1 envelope proteins is critical for the design of an effective vaccine. Despite the availability of many high-resolution structures, key functional correlates in the envelope trimer remain undefined. We utilized a combination of structural analysis, in silico energy calculation, mutagenesis, and neutralization profiling to dissect the functional anatomy of the trimer apex, which acts as a global regulator of the HIV-1 spike conformation. We identify four hydrophobic clusters that stabilize the spike in a tightly closed configuration and, thereby, play a critical role in protecting it from the reach of neutralizing antibodies.
Reaction Paths of Keto−Enol Tautomerization of β-Diketones

Density functional theory calculations were conducted on the title reactions with water molecules. Malonaldehyde, acetylacetone, and malonic acid were adopted as reactants. A reaction of malonaldehyde and (2 + 2) water molecules was found to proceed by a small (ca. 7 kcal/mol) activation energy. Two are reactant and two are catalyst molecules, respectively. The intramolecular hydrogen bond in the enol form is disrupted by the intermolecular one. Tautomerization transition-state geometries for acetylacetone and malonic acid are similar to that of malonaldehyde. Without the enhanced reactivity of water hydrogen-bond networks, tautomerization reactions undergo large activation energies. Various reaction models of (malonaldehyde)n (n = 2, 3, and 4) have given the energetic result. The keto−enol tautomerization has an analogy with the bimolecular nucleophilic elimination (E2) mechanism.
Asymptotic analysis of small‐angle scattering intensities of plane columnar layers

The asymptotic behaviour, at large scattering vector q , of the small-angle scattering intensities of isotropic plane samples is similar to that of three-dimensional samples. In fact, its expression, limited to the ﬁrst two leading terms, is c 1 γ (1) (0) /q 3 + c 3 γ (3) (0) /q 5 , where c 1 and c 3 are appropriate numerical constants and γ (1) (0) and γ (3) (0) the values, at the origin, of the ﬁrst and third derivatives of the two-dimensional correlation function. These values are proportional to the speciﬁc length and to the mean square reciprocal curvature radius of the interface curve. The angularity of the latter can also be determined, while the presence of oscillations in the appropriate Porod plot is related to a parallelism condition obeyed by the interface curve. These results are useful for analysing the small-angle scattering intensities collected under grazing incidence and diﬀused by ﬁlm samples that are a collection of homogeneous cylinders of arbitrary right sections.
A comfortable steady state visual evoked potential stimulation paradigm using peripheral vision

Objective. Steady-state visual evoked potential (SSVEP)-brain–computer interfaces (BCIs) can cause much visual discomfort if the users use the SSVEP-BCIs for a long time. As an alternative scheme to reduce users’ visual fatigue, this study proposes a new stimulation paradigm (termed as steady state peripheral visual evoked potential, abbreviated as SSPVEP) which makes full use of peripheral vision. The electroencephalography (EEG) signals are classifiable which means this proposed stimulation paradigm can be used in BCI system with the aid of the latest hybrid signal processing approach. Approach. Under the SSPVEP stimulation paradigm, 20 targets are mounted on 20 frequencies and other targets are set between two targets with flicker stimuli coding. In order to ensure the classification accuracy of SSPVEP signal detection under the proposed stimulation paradigm, two optimization schemes are proposed for the detection stage of the conventional ensemble task-related component analysis (ETRCA) algorithm. The first optimization scheme uses nonlinear correlation coefficient at the detection part for the first time to improve the classification accuracy of the system. The second optimization scheme uses γ correction to enhance the time domain features of the SSPVEP signals, and uses Manhattan distance for the final detection. Main results. According to the response waveforms of the EEG signals generated under the SSPVEP stimulation paradigm and the results of the questionnaire on user’s comfort level to the two stimulation paradigms (SSPVEP paradigm and conventional SSVEP paradigm), the proposed stimulation paradigm brings less visual fatigue. The comparison results indicate that the proposed detection methods (ETRCA + γ correction + Manhattan distance, ETRCA + Spearman correlation) can greatly improve the classification accuracy compared with the individual template canonical correlation analysis method and conventional ETRCA method based on Pearson correlation. Significance. The SSPVEP stimulation paradigm reduces users’ visual fatigue via using peripheral vision, which provides a new design idea for SSVEP stimulation paradigm aimed at visual comfort.
Simultaneous determination and dietary risk assessment of clethodim and its metabolites in different fruits and vegetables

ABSTRACT Clethodim is one of the most widely used herbicides in agriculture and, after field application, is metabolised to several metabolites. The potential toxicological negative effects of these compounds are poorly understood. Thus, recently, within the risk assessment framework, the European Food Safety Authority (EFSA) proposed to include the minor metabolites in the definition of clethodim residue. In this work, an easy to use and reliable UHPLC method coupled with a triple quadrupole MS/MS was developed and validated for the detection and quantification of the herbicide clethodim and related metabolites clethodim sulphone, clethodim sulphoxide, metabolites M17R and M18R in apple, grape, olive and rice. The five analytes were extracted by using a modified QuEChERS procedure, while the active ingredients were determined in multiple reaction monitoring (MRM) ion-switching mode. The proposed method showed calibration curve linearity with r2 ≥ 0.990 for all active ingredients (a.is.) both in solvent and matrix extracts. Limits of quantitation (LOQ) of the five compounds ranged from 9.44 µg/kg for M17R in olive extract to 11.01 µg/kg for clethodim in apple extract. Recoveries values ranged from 86% to 119% at two concentration levels (LOQ and 10xLOQ), while the intraday and interday precisions of the method were both below 10% in all cases. The method was successfully used for the quantification of the five a.is. in different food matrices. Furthermore, chronic dietary risk was investigated using a hazard quotients (HQ) method based on European dietary habits. The chronic dietary exposure risk quotients ranged from 1.0 × 10−5 (lower bound scenario) to 2.7 × 10−4 (upper bound scenario) which were significantly lower than 1. Data obtained indicate that the dietary exposure risks were acceptable for clethodim and its major and minor metabolites applied in apple, table grape, rice and table olive.
Effects of maternal folic acid supplementation on nuclear methyltransferase activity of adult rats subjected to an animal model of schizophrenia

Schizophrenia is considered one of the most disabling and severe human diseases worldwide. The etiology of schizophrenia is thought to be multifactorial and evidence suggests that DNA methylation can play an important role in underlying pivotal neurobiological alterations of this disorder. Some studies have demonstrated the effects of dietary supplementation as an alternative approach to the prevention of schizophrenia, including folic acid. However, no study has ever investigated the role of such supplementation in altering the DNA methylation system in the context of schizophrenia.
Touch‐Based Stressless Cortisol Sensing

Tracking fluctuations of the cortisol level is important in understanding the body's endocrine response to stress stimuli. Traditional cortisol sensing relies on centralized laboratory settings, while wearable cortisol sensors are limited to slow and complex assays. Here, a touch‐based non‐invasive molecularly imprinted polymer (MIP) electrochemical sensor for rapid, simple, and reliable stress‐free detection of sweat cortisol is described. The sensor readily measures fingertip sweat cortisol via highly selective binding to the cortisol‐imprinted electropolymerized polypyrrole coating. The MIP network is embedded with Prussian blue redox probes that offer direct electrical signaling of the binding event to realize sensitive label‐free amperometric detection. Using a highly permeable sweat‐wicking porous hydrogel, instantaneously secreted fingertip sweat can be conveniently and rapidly collected without any assistance. By eliminating time lags, such rapid (3.5 min) fingertip assay enables the capture of sharp variations in cortisol levels, compared to previous methods. Such advantages are demonstrated by tracking cortisol response in short cold‐pressor tests and throughout day‐long circadian rhythm, along with gold‐standard immunoassay validation. A stretchable epidermal MIP sensor is also described for directly tracking cortisol in exercise‐induced sweat. The rapid touch‐based cortisol sensor offers an attractive, accessible, stressless avenue for quantitative stress management.
Machine Learning Methods to Predict the Terrestrial and Marine Origin of Natural Products

In recent years there has been a growing interest in studying the differences between the chemical and biological space represented by natural products (NPs) of terrestrial and marine origin. In order to learn more about these two chemical spaces, marine natural products (MNPs) and terrestrial natural products (TNPs), a machine learning (ML) approach was developed in the current work to predict three classes, MNPs, TNPs and a third class of NPs that appear in both the terrestrial and marine environments. In total 22,398 NPs were retrieved from the Reaxys® database, from those 10,790 molecules are recorded as MNPs, 10,857 as TNPs, and 761 NPs appear registered as both MNPs and TNPs. Several ML algorithms such as Random Forest, Support Vector Machines, and deep learning Multilayer Perceptron networks have been benchmarked. The best performance was achieved with a consensus classification model, which predicted the external test set with an overall predictive accuracy up to 81 %. As far as we know this approach has never been intended and therefore allow to be used to better understand the chemical space defined by MNPs, TNPs or both, but also in virtual screening to define the applicability domain of QSAR models of MNPs and TNPs.