Miracle-dz/UniFAR-FTUs huggingface dataset:
Gut Microbiota as an Objective Measurement for Auxiliary Diagnosis of Insomnia Disorder

Insomnia is a type of sleep disorder which is associated with various diseases’ development and progression, such as obesity, type II diabetes and cardiovascular diseases. Recent investigation of the gut-brain axis enhances our understanding of the role of the gut microbiota in brain-related diseases. However, whether the gut microbiota is associated with insomnia remains unknown. In the present investigation, leveraging the 16S rDNA amplicon sequencing of V3-V4 region and the novel bioinformatic analysis, it was demonstrated that between insomnia and healthy populations, the composition, diversity and metabolic function of the gut microbiota are significantly changed. Other than these, redundancy analysis, co-occurrence analysis and PICRUSt underpin the gut taxa composition, signaling pathways, and metabolic functions perturbed by insomnia disorder. Moreover, random forest together with cross-validation identified two signature bacteria, which could be used to distinguish the insomnia patients from the healthy population. Furthermore, based on the relative abundance and clinical sleep parameter, we constructed a prediction model utilizing artificial neural network (ANN) for auxiliary diagnosis of insomnia disorder. Overall, the aforementioned study provides a comprehensive understanding of the link between the gut microbiota and insomnia disorder.
Monocyte-Derived Dendritic Cells Dictate the Memory Differentiation of CD8+ T Cells During Acute Infection

Monocyte-derived dendritic cells (moDCs) have been shown to robustly expand during infection; however, their roles in anti-infectious immunity remain unclear. Here, we found that moDCs were dramatically increased in the secondary lymphoid organs during acute LCMV infection in an interferon-γ (IFN-γ)-dependent manner. We also found that priming by moDCs enhanced the differentiation of memory CD8+ T cells compared to differentiation primed by conventional dendritic cells (cDCs) through upregulation of Eomesodermin (Eomes) and T cell factor-1 (TCF-1) expression in CD8+ T cells. Consequently, impaired memory formation of CD8+ T cells in mice that had reduced numbers of moDCs led to defective clearance of pathogens upon rechallenge. Mechanistically, attenuated interleukin-2 (IL-2) signaling in CD8+ T cells primed by moDCs was responsible for the enhanced memory programming of CD8+ T cells. Therefore, our findings unveil a specialization of the antigen-presenting cell subsets in the fate determination of CD8+ T cells during infection and pave the way for the development of a novel therapeutic intervention on infection.
Der Euro und Weiterführende Regionale Preiskonvergenz? Resultate aus der ‘Groß-Region’ um Luxemburg

Abstract This article uses individual supermarket prices and analyses to what extent absolute deviations from the law of one price are attributable to transaction costs. The results indicate that absolute percentage price differences increase with distance, but at a decreasing rate. Similarly, crossing borders increases price deviations, while being inside the former Belgo-Luxembourg currency union has the opposite effect. This result nurtures the hopes that the euro may be able to reduce regional and cross-border price differences in the long term.
Variables Influencing the Effectiveness of Creatine Supplementation as a Therapeutic Intervention for Sarcopenia

Sarcopenia is an age-related muscle condition characterized by a reduction in muscle quantity, force generating capacity and physical performance. Sarcopenia occurs in 8–13% of adults ≥ 60 years of age and can lead to disability, frailty, and various other diseases. Over the past few decades, several leading research groups have focused their efforts on developing strategies and recommendations for attenuating sarcopenia. One potential nutritional intervention for sarcopenia is creatine supplementation. However, research is inconsistent regarding the effectiveness of creatine on aging muscle. The purpose of this perspective paper is to: (1) propose possible reasons for the inconsistent responsiveness to creatine in aging adults, (2) discuss the potential mechanistic actions of creatine on muscle biology, (3) determine whether the timing of creatine supplementation influences aging muscle, (4) evaluate the evidence investigating the effects of creatine with other compounds (protein, conjugated linoleic acid) in aging adults, and (5) provide insight regarding the safety of creatine for aging adults.
Response: Commentary: Tropical fish diversity enhances coral reef functioning across multiple scales

1 Tennenbaum Marine Observatories Network, MarineGEO, Smithsonian Environmental Research Center, Edgewater, MD, United States, Department of Biological Sciences, Simon Fraser University, Burnaby, BC, Canada, Department of Biological and Environmental Sciences, College of the Environment and Life Sciences, University of Rhode Island, Kingston, RI, United States, Darling Marine Center, University of Maine, Walpole, ME, United States, 5 Reef Check Dominican Republic, Santo Domingo, Dominican Republic, 6 Bigelow Laboratory for Ocean Sciences, East Boothbay, ME, United States
Common Molecular Alterations in Canine Oligodendroglioma and Human Malignant Gliomas and Potential Novel Therapeutic Targets

Spontaneous canine (Canis lupus) oligodendroglioma (ODG) holds tremendous potential as an immunocompetent large animal model of human malignant gliomas (MG). However, the feasibility of utilizing this model in pre-clinical studies depends on a thorough understanding of the similarities and differences of the molecular pathways associated with gliomas between the two species. We have previously shown that canine ODG has an immune landscape and expression pattern of commonly described oncogenes similar to that of human MG. In the current study, we performed a comprehensive analysis of canine ODG RNAseq data from 4 dogs with ODG and 2 normal controls to identify highly dysregulated genes in canine tumors. We then evaluated the expression of these genes in human MG using Xena Browser, a publicly available database. STRING-database inquiry was used in order to determine the suggested protein associations of these differentially expressed genes as well as the dysregulated pathways commonly enriched by the protein products of these genes in both canine ODG and human MG. Our results revealed that 3,712 (23%) of the 15,895 differentially expressed genes demonstrated significant up- or downregulation (log2-fold change > 2.0). Of the 3,712 altered genes, ~50% were upregulated (n = 1858) and ~50% were downregulated (n = 1854). Most of these genes were also found to have altered expression in human MG. Protein association and pathway analysis revealed common pathways enriched by members of the up- and downregulated gene categories in both species. In summary, we demonstrate that a similar pattern of gene dysregulation characterizes both human MG and canine ODG and provide additional support for the use of the canine model in order to therapeutically target these common genes. The results of such therapeutic targeting in the canine model can serve to more accurately predict the efficacy of anti-glioma therapies in human patients.
IS256-Mediated Overexpression of the WalKR Two-Component System Regulon Contributes to Reduced Vancomycin Susceptibility in a Staphylococcus aureus Clinical Isolate

Vancomycin (VAN)-intermediate-resistant Staphylococcus aureus (VISA) is continually isolated globally, with a systematic review suggesting a prevalence of 2% in all blood culture samples. Most VISA strains exhibit common characteristics, such as a thickened cell wall, reduced autolysis, and attenuated virulence. Here, based on multi-omics approaches, we have characterized clinical VISA isolates obtained through prolonged antimicrobial treatment in a single patient. All VISA isolates were isogenic, based on multi-locus sequence typing (MLST) ST5, SCCmec type II (2A), and spa type t17639. Core-genome single nucleotide variations (SNVs) found among thirteen isolates during the patient’s hospitalization, indicated clonality, but not notable genetic features of the VISA phenotype. We determined the complete genome sequence of VAN-susceptible strain KG-03 (minimum inhibitory concentration [MIC] 0.5 μg/mL) and two VISA strains, KG-18 and KG-22 (MIC 8.0 and 4.0 μg/mL, respectively). Comparative genome analysis showed remarkable strain-specific IS256 insertions. RNA-Seq transcriptome analysis revealed IS256-mediated overexpression of the walKR two-component system in VISA KG-18, possibly leading to modulation of cell wall integrity (lytM and sceD) and surface charge (mprF and dltABCD). In addition, secretome analysis indicated that cell wall-anchored proteins (Protein A, SasG, and SdrD) were significantly decreased. KG-18 and KG-22 exhibit thickened cell wall, and are relatively resistant to lysostaphin, which cleaves a staphylococcus-unique pentaglycine chain in the peptidoglycan. We conclude that KG-18 achieved reduced susceptibility to VAN by IS256-mediated WalKR overexpression, leading to a markedly thickened cell wall for trapping free VAN molecules with redundant D-Ala-D-Ala targets. In addition, a positively charged surface with lysyl-phosphatidylglycerol and depolarization of wall teichoic acid could contribute to inhibiting cationic daptomycin and VAN antimicrobial activity. Comparative omics approaches in this study strongly suggest that fully complete and annotated genome sequences will be indispensable for characterizing overall VISA phenotype.
Cannabidivarin Treatment Ameliorates Autism-Like Behaviors and Restores Hippocampal Endocannabinoid System and Glia Alterations Induced by Prenatal Valproic Acid Exposure in Rats

Autism spectrum disorder (ASD) is a developmental condition whose primary features include social communication and interaction impairments with restricted or repetitive motor movements. No approved treatment for the core symptoms is available and considerable research efforts aim at identifying effective therapeutic strategies. Emerging evidence suggests that altered endocannabinoid signaling and immune dysfunction might contribute to ASD pathogenesis. In this scenario, phytocannabinoids could hold great pharmacological potential due to their combined capacities to act either directly or indirectly on components of the endocannabinoid system and to modulate immune functions. Among all plant-cannabinoids, the phytocannabinoid cannabidivarin (CBDV) was recently shown to reduce motor impairments and cognitive deficits in animal models of Rett syndrome, a condition showing some degree of overlap with autism, raising the possibility that CBDV might have therapeutic potential in ASD. Here, we investigated the ability of CBDV treatment to reverse or prevent ASD-like behaviors in male rats prenatally exposed to valproic acid (VPA; 500 mg/kg i.p.; gestation day 12.5). The offspring received CBDV according to two different protocols: symptomatic (0.2/2/20/100 mg/kg i.p.; postnatal days 34–58) and preventative (2/20 mg/kg i.p.; postnatal days 19–32). The major efficacy of CBDV was observed at the dose of 20 mg/kg for both treatment schedules. CBDV in symptomatic rats recovered social impairments, social novelty preference, short-term memory deficits, repetitive behaviors and hyperlocomotion whereas preventative treatment reduced sociability and social novelty deficits, short-term memory impairments and hyperlocomotion, without affecting stereotypies. As dysregulations in the endocannabinoid system and neuroinflammatory markers contribute to the development of some ASD phenotypes in the VPA model, neurochemical studies were performed after symptomatic treatment to investigate possible CBDV’s effects on the endocannabinoid system, inflammatory markers and microglia activation in the hippocampus and prefrontal cortex. Prenatal VPA exposure increased CB1 receptor, FAAH and MAGL levels, enhanced GFAP, CD11b, and TNFα levels and triggered microglia activation restricted to the hippocampus. All these alterations were restored after CBDV treatment. These data provide preclinical evidence in support of the ability of CBDV to ameliorate behavioral abnormalities resembling core and associated symptoms of ASD. At the neurochemical level, symptomatic CBDV restores hippocampal endocannabinoid signaling and neuroinflammation induced by prenatal VPA exposure.
Integrated 3D anatomical model for automatic myocardial segmentation in cardiac CT imagery

ABSTRACT Segmentation of epicardial and endocardial boundaries is a critical step in diagnosing cardiovascular function in heart patients. The manual tracing of organ contours in computed tomography angiography (CTA) slices is subjective, time-consuming and impractical in clinical setting. We propose a novel multidimensional automatic edge detection algorithm based on shape priors and principal component analysis (PCA). We have developed a highly customised parametric model for implicit representations of segmenting curves (3D) for left ventricle (LV), right ventricle (RV) and epicardium (Epi) used simultaneously to achieve myocardial segmentation. We have combined these representations in a region-based image modelling framework with high-level constraints enabling the modelling of complex cardiac anatomical structures to automatically guide the segmentation of endo/epicardial boundaries. Test results on 30 short-axis CTA datasets show robust segmentation with error (mean std mm) of (1.46 0.41), (2.06 0.65) and (2.88 0.59) for LV, RV and Epi, respectively.
The Identification and Analysis of mRNA–lncRNA–miRNA Cliques From the Integrative Network of Ovarian Cancer

Ovarian cancer is one of the leading causes of cancer mortality in women. Since little clinical symptoms were shown in the early period of ovarian cancer, most patients were found in phases III–IV or with abdominal metastasis when diagnosed. The lack of effective early diagnosis biomarkers makes ovarian cancer difficult to screen. However, in essence, the fundamental problem is we know very little about the regulatory mechanisms during tumorigenesis of ovarian cancer. There are emerging regulatory factors, such as long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), which have played important roles in cancers. Therefore, we analyzed the RNA-seq profiles of 407 ovarian cancer patients. An integrative network of 20,424 coding RNAs (mRNAs), 10,412 lncRNAs, and 742 miRNAs were construed with variance inflation factor (VIF) regression method. The mRNA–lncRNA–miRNA cliques were identified from the network and analyzed. Such promising cliques showed significant correlations with survival and stage of ovarian cancer and characterized the complex sponge regulatory mechanism, suggesting their contributions to tumorigenicity. Our results provided novel insights of the regulatory mechanisms among mRNAs, lncRNAs, and miRNAs and highlighted several promising regulators for ovarian cancer detection and treatment.
Host Microbe Interactions in the Lactating Mammary Gland

The bacteria present in human milk constitute the human milk microbiome (hMM). Both the older culture-based work and the more recent studies using molecular detection of bacterial DNA have reached similar conclusions: the hMM mostly consists of commensal staphylococci such as Staphylococcus epidermidis, and streptococci. The prevalence of other bacterial groups such lactobacilli varies widely, while the abundance and prevalence of bifidobacteria is generally low. Recently, the hMM became accepted as a part of a physiologically normal state with suggested potential health benefits. Most research on the hMM has focused on its composition and potential effect on the breastfed infant. A major role as a microbiome inoculum for the infant gut has been proposed, but remains to be clearly demonstrated. Herein, we also discuss the emerging connection between the hMM and mammary gland physiology and lactation. Similarities between the mammary gland and mucosal interfaces are considerable, and in particular mucosal-like immune attributes of mammary gland. The potential role of hMM-host interactions in the mammary gland in maternal health is explored with a primary focus on lactational mastitis.
Apical Trafficking Pathways of Influenza A Virus HA and NA via Rab17- and Rab23-Positive Compartments

The envelope proteins of influenza A virus, hemagglutinin (HA) and neuraminidase (NA), play critical roles in viral entry to host cells and release from the cells, respectively. After protein synthesis, they are transported from the trans-Golgi network (TGN) to the apical plasma membrane (PM) and assembled into virus particles. However, the post-TGN transport pathways of HA and NA have not been clarified. Temporal study by confocal microscopy revealed that HA and NA colocalized soon after their synthesis, and relocated together from the TGN to the upper side of the cell. Using the Rab family protein, we investigated the post-TGN transport pathways of HA and NA. HA partially colocalized with AcGFP-Rab15, Rab17, and Rab23, but rarely with AcGFP-Rab11. When analyzed in cells stably expressing AcGFP-Rab, HA/NA colocalized with Rab15 and Rab17, markers of apical sorting and recycling endosomes, and later colocalized with Rab23, which distributes to the apical PM and endocytic vesicles. Overexpression of the dominant-negative (DN) mutants of Rab15 and Rab17, but not Rab23, significantly delayed HA transport to the PM. However, Rab23DN impaired cell surface expression of HA. Live-cell imaging revealed that NA moved rapidly with Rab17 but not with Rab15. NA also moved with Rab23 in the cytoplasm, but this motion was confined at the upper side of the cell. A fraction of HA was localized to Rab17 and Rab23 double-positive vesicles in the cytoplasm. Coimmunoprecipitation indicated that HA was associated with Rab17 and Rab23 in lipid raft fractions. When cholesterol was depleted by methyl-β-cyclodextrin treatment, the motion of NA and Rab17 signals ceased. These results suggest that HA and NA are incorporated into lipid raft microdomains and are cotransported to the PM by Rab17-positive and followed by Rab23-positive vesicles.
Blimp-1 Contributes to the Development and Function of Regulatory B Cells

Regulatory B cells (Bregs) are a B cell subset that plays a suppressive role in immune responses. The CD19+CD1dhiCD5+ Bregs that can execute regulatory functions via secreting IL-10 are defined as B10 cells. Bregs suppress autoimmune and inflammatory diseases, whereas they exacerbate infectious diseases caused by bacteria, viruses, or parasites. Notably, the molecular mechanisms regulating the development and functions of Bregs are still largely unknown. Furthermore, the biological impact of Bregs in fungal infection has not yet been demonstrated. Here, we compared the gene expression profiles of IL-10-producing and –non-producing mouse splenic B cells stimulated with lipopolysaccharide (LPS) or anti-CD40 antibody. Blimp-1, a transcription factor known to be critical for plasma cell differentiation, was found to be enriched in the IL-10-producing B cells. The frequency of Blimp-1+ B10 cells was increased in LPS-treated mice and in isolated B10 cells that were stimulated with LPS. Surprisingly, B cell-specific Blimp-1 knockout (Cko) mice, generated by CD19 promoter driven Cre recombinase-dependent deletion of Prdm1 (gene encoding Blimp-1), showed higher frequencies of B10 cells both in the steady state and following injection with LPS, as compared with control littermates. However, B10 cells lacking Blimp-1 failed to efficiently suppress the proliferation of naïve CD4+ T cells primed with anti-CD3 and anti-CD28 antibodies. B10 cells can be stimulated for further differentiation into plasmablasts, and a subset of plasmablasts express IL-10. We found that B10 cells from Cko mice failed to generate both IL-10-non-producing and IL-10-producing plasmablasts. Mechanistically, we found that Blimp-1 can directly suppress Il-10, whereas, in the presence of activated STAT3, Blimp-1 works together with activated STAT3 to upregulate Il-10. Moreover, we also found that B10 cells improve the clearance of Candida albicans infection but worsen the infection mortality. Notably, a lack of Blimp-1 in B10 cells did not change these effects of adoptively transferred B10 cells on fungal infections. Together, our data show that Blimp-1 regulates the generation, differentiation, and IL-10 production of Bregs.
The DNA Methylation Inhibitor Zebularine Controls CD4+ T Cell Mediated Intraocular Inflammation

CD4+ T cell mediated uveitis is conventionally treated with systemic immunosuppressive agents, including corticosteroids and biologics targeting key inflammatory cytokines. However, their long-term utility is limited due to various side effects. Here, we investigated whether DNA methylation inhibitor zebularine can target CD4+ T cells and control intraocular inflammation. Our results showed that zebularine restrained the expression of inflammatory cytokines IFN-γ and IL-17 in both human and murine CD4+ T cells in vitro. Importantly, it also significantly alleviated intraocular inflammation and retinal tissue damage in the murine experimental autoimmune uveitis (EAU) model in vivo, suggesting that the DNA methylation inhibitor zebularine is a candidate new therapeutic agent for uveitis.
Crystal structure of diaqua-bis(pyridine)-μ2-squarato(1,3)cobalt(II), Co(C4O4)(C5H5N)2(H2O)2

Abstract C14H14N2CoO6, orthorhombic, Pbca (no. 61), a = 11.325(2) Å,b = 7.959(1) Å, c = 16.664(3) Å, V = 1502.0 Å3, Z = 4, Rgt(F) = 0.023, wRref(F2) = 0.060, T = 293 K.
Crystal structure of 2-((1-(1-adamantyl)ethyl)iminomethyl)phenol, C19H25NO

Abstract C19H25NO, monoclinic, P1211 (no. 4), a = 6.4436(8) Å, b = 16.438(2) Å, c = 15.340(2) Å, β = 98.536(2)°, V = 1606.9 Å3, Z = 4, Rgt(F) = 0.079, wRref(F2) = 0.172, T = 293 K.
Baseball Errors

This paper examines the factors that determine the rate of errors called in major league baseball, and changes in the error rate over time. We find that (1) the rate of errors depends on the quality of play and characteristics of the field, but that (2) these do not fully explain variations in the error rate. With regard to point 1, we find that the error rate is higher when the quality of fielding is suspect, i.e., the performance of an expansion team in its first year, or the fielding done by replacement players during World War II, and lower when playing conditions are better, e.g. on artificial turf and during night games. With regard to point 2, we find evidence that official scorers are biased toward the home team, but that the bias declined when the stakes involved increased, with the advent of arbitration and free agency.
Crystal structure of pentamethylpyrylium triiodide, [(CH3)5C5O][I3]

Abstract C10H15I3O, orthorhombic, Pnma (no. 62), a = 13.750(3) Å, b = 7.288(2) Å, c = 15.140(3) Å, V = 1517.2 Å3, Z = 4, Rgt(F) = 0.031, wRref(F2) = 0.071, T = 150 K.
Inhibition of cathepsin B reduces β-amyloid production in regulated secretory vesicles of neuronal chromaffin cells: evidence for cathepsin B as a candidate β-secretase of Alzheimer's disease

1 Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093, USA 2 Department of Pathology, Stanford University, Palo Alto, CA 94305, USA 3 Department of Pharmaceutical Chemistry, School of Pharmacy, University of California at San Francisco, San Francisco, CA 94143, USA 4 Harvard University Microchemistry and Proteomics Analysis Facility, Cambridge, MA 02138, USA 5 American Life Science Pharmaceuticals, Inc., San Diego, CA 92121, USA