Miracle-dz/UniFAR-FTUs huggingface dataset:
Fusion of near-infrared and fluorescence spectroscopy for untargeted fraud detection of Chinese tea seed oil using chemometric methods.

BACKGROUND This paper investigated the feasibility of data fusion of near-infrared (NIR) and fluorescence spectroscopy for rapid analysis of cheap vegetable oils in Chinese Camellia oleifera Abel. (COA) oil. Because practical frauds usually involve adulterations of multiple known and unknown cheap oils, traditional analytical methods aimed at detecting one or more known adulterants are insufficient to identify adulterated COA oil. Therefore, untargeted analysis was performed by developing class models of pure COA oil using robust one-class partial least squares (OCPLS). RESULTS The most accurate OCPLS model was obtained with fusion of standard normal variate (SNV)-NIR and SNV-fluorescence spectra with sensitivity of 0.954 and specificity of 0.91. Robust OCPLS could detect adulterations with 2% (w/w) or more cheap oils, including rapeseed oil, sunflower seed oil, corn oil and peanut oil. CONCLUSION Fusion of NIR and fluorescence data and chemometrics provided enhanced capacity for rapid and untargeted analysis of multiple adulterations in Chinese COA oils. © 2018 Society of Chemical Industry.
GLP-1 Improves Adipocyte Insulin Sensitivity Following Induction of Endoplasmic Reticulum Stress

Glucagon-like peptide 1 (GLP-1) improves insulin resistance of adipose tissue in obese humans. However, the mechanism of this effect is unclear. Perturbation of endoplasmic reticulum (ER) homeostasis impairs insulin signaling. We hypothesized that GLP-1 could directly improve insulin signaling in ER-stressed adipocytes. Here, we examined the effects of GLP-1 on ER stress response in fat cells in an obese and insulin-resistant murine model. We found that GLP-1 analog liraglutide reduced ER stress related gene expression in visceral fat cells accompanied by improved systemic insulin tolerance. Consistently, GLP-1 decreased CHOP expression and increased insulin stimulated AKT phosphorylation (p-AKT) in thapsigargin, a ER stress inducer, treated white fat cells differentiated from visceral stromal vascular fraction. We further found blocking CHOP expression increased insulin stimulated p-AKT in ER-stressed fat cells. Of note, we found mTOR signaling pathway contributed to the expression of ATF4 and subsequently the CHOP expression in ER stress response, while GLP-1 inhibited mTOR activity as exemplified by elevated autophagosome formation and increased LC3II/LC3I ratio. These findings suggest that GLP-1 directly modulates the ER stress response partially via inhibiting mTOR signaling pathway, leading to increased insulin sensitivity in adipocytes.
A Novel Subfamily of Bacterial AAT-Fold Basic Amino Acid Decarboxylases and Functional Characterization of Its First Representative: Pseudomonas aeruginosa LdcA

Abstract Polyamines are small amino-acid derived polycations capable of binding negatively charged macromolecules. Bacterial polyamines are structurally and functionally diverse, and are mainly produced biosynthetically by pyridoxal-5-phosphate-dependent amino acid decarboxylases referred to as Lysine-Arginine-Ornithine decarboxylases (LAOdcs). In a phylogenetically limited group of bacteria, LAOdcs are also induced in response to acid stress. Here, we performed an exhaustive phylogenetic analysis of the AAT-fold LAOdcs which showcased the ancient nature of their short forms in Cyanobacteria and Firmicutes, and emergence of distinct subfamilies of long LAOdcs in Proteobacteria. We identified a novel subfamily of lysine decarboxylases, LdcA, ancestral in Betaproteobacteria and Pseudomonadaceae. We analyzed the expression of LdcA from Pseudomonas aeruginosa, and uncovered its role, intimately linked to cadaverine (Cad) production, in promoting growth and reducing persistence of this multidrug resistant human pathogen during carbenicillin treatment. Finally, we documented a certain redundancy in the function of the three main polyamines—Cad, putrescine (Put), and spermidine (Spd)—in P. aeruginosa by demonstrating the link between their intracellular level, as well as the capacity of Put and Spd to complement the growth phenotype of the ldcA mutant.
Involvement of O-GlcNAcylation in the Skeletal Muscle Physiology and Physiopathology: Focus on Muscle Metabolism

Skeletal muscle represents around 40% of whole body mass. The principal function of skeletal muscle is the conversion of chemical energy toward mechanic energy to ensure the development of force, provide movement and locomotion, and maintain posture. This crucial energy dependence is maintained by the faculty of the skeletal muscle for being a central place as a “reservoir” of amino acids and carbohydrates in the whole body. A fundamental post-translational modification, named O-GlcNAcylation, depends, inter alia, on these nutrients; it consists to the transfer or the removal of a unique monosaccharide (N-acetyl-D-glucosamine) to a serine or threonine hydroxyl group of nucleocytoplasmic and mitochondrial proteins in a dynamic process by the O-GlcNAc Transferase (OGT) and the O-GlcNAcase (OGA), respectively. O-GlcNAcylation has been shown to be strongly involved in crucial intracellular mechanisms through the modulation of signaling pathways, gene expression, or cytoskeletal functions in various organs and tissues, such as the brain, liver, kidney or pancreas, and linked to the etiology of associated diseases. In recent years, several studies were also focused on the role of O-GlcNAcylation in the physiology and the physiopathology of skeletal muscle. These studies were mostly interested in O-GlcNAcylation during muscle exercise or muscle-wasting conditions. Major findings pointed out a different “O-GlcNAc signature” depending on muscle type metabolism at resting, wasting and exercise conditions, as well as depending on acute or long-term exhausting exercise protocol. First insights showed some differential OGT/OGA expression and/or activity associated with some differential stress cellular responses through Reactive Oxygen Species and/or Heat-Shock Proteins. Robust data displayed that these O-GlcNAc changes could lead to (i) a differential modulation of the carbohydrates metabolism, since the majority of enzymes are known to be O-GlcNAcylated, and to (ii) a differential modulation of the protein synthesis/degradation balance since O-GlcNAcylation regulates some key signaling pathways such as Akt/GSK3β, Akt/mTOR, Myogenin/Atrogin-1, Myogenin/Mef2D, Mrf4 and PGC-1α in the skeletal muscle. Finally, such involvement of O-GlcNAcylation in some metabolic processes of the skeletal muscle might be linked to some associated diseases such as type 2 diabetes or neuromuscular diseases showing a critical increase of the global O-GlcNAcylation level.
EWASdb: epigenome-wide association study database

Abstract DNA methylation, the most intensively studied epigenetic modification, plays an important role in understanding the molecular basis of diseases. Furthermore, epigenome-wide association study (EWAS) provides a systematic approach to identify epigenetic variants underlying common diseases/phenotypes. However, there is no comprehensive database to archive the results of EWASs. To fill this gap, we developed the EWASdb, which is a part of 'The EWAS Project', to store the epigenetic association results of DNA methylation from EWASs. In its current version (v 1.0, up to July 2018), the EWASdb has curated 1319 EWASs associated with 302 diseases/phenotypes. There are three types of EWAS results curated in this database: (i) EWAS for single marker; (ii) EWAS for KEGG pathway and (iii) EWAS for GO (Gene Ontology) category. As the first comprehensive EWAS database, EWASdb has been searched or downloaded by researchers from 43 countries to date. We believe that EWASdb will become a valuable resource and significantly contribute to the epigenetic research of diseases/phenotypes and have potential clinical applications. EWASdb is freely available at http://www.ewas. org.cn/ewasdb or http://www.bioapp. org/ewasdb.
Structural basis of the specific interaction of SMRT corepressor with histone deacetylase 4

Abstract Modification of chromatin and related transcription factors by histone deacetylases (HDACs) is one of the major strategies for controlling gene expression in eukaryotes. The HDAC domains of class IIa HDACs repress the respective target genes by interacting with the C-terminal region of the silencing mediator for retinoid and thyroid receptor (SMRT) repression domain 3 (SRD3c). However, latent catalytic activity suggests that their roles as deacetylases in gene regulation are unclear. Here, we found that two conserved GSI-containing motifs of SRD3c are critical for HDAC4 binding. Two SMRT peptides including these motifs commonly form a β-hairpin structure in the cleft and block the catalytic entry site of HDAC4. They interact mainly with class IIa HDAC-specific residues of HDAC4 in a closed conformation. Structure-guided mutagenesis confirmed critical interactions between the SMRT peptides and HDAC4 and –5 as well as the contribution of the Arg1369 residue in the first motif for optimal binding to the two HDACs. These results indicate that SMRT binding does not activate the cryptic deacetylase activity of HDAC4 and explain how class IIa HDACs and the SMRT-HDAC3 complex are coordinated during gene regulation.
Prudent Design Principles for Information Flow Control

Recent years have seen a proliferation of research on information flow control. While the progress has been tremendous, it has also given birth to a bewildering breed of concepts, policies, conditions, and enforcement mechanisms. Thus, when designing information flow controls for a new application domain, the designer is confronted with two basic questions: (i) What is the right security characterization for a new application domain? and (ii) What is the right enforcement mechanism for a new application domain? This paper puts forward six informal principles for designing information flow security definitions and enforcement mechanisms: attacker-driven security, trust-aware enforcement, separation of policy annotations and code, language-independence, justified abstraction, and permissiveness. We particularly highlight the core principles of attacker-driven security and trust-aware enforcement, giving us a rationale for deliberating over soundness vs. soundiness. The principles contribute to roadmapping the state of the art in information flow security, weeding out inconsistencies from the folklore, and providing a rationale for designing information flow characterizations and enforcement mechanisms for new application domains.
Proton magnetic resonance spectroscopy lactate/N-acetylaspartate within 2 weeks of birth accurately predicts 2-year motor, cognitive and language outcomes in neonatal encephalopathy after therapeutic hypothermia

Objective Brain proton (1H) magnetic resonance spectroscopy (MRS) lactate/N-acetylaspartate (Lac/NAA) peak area ratio is used for prognostication in neonatal encephalopathy (NE). At 3 Tesla in NE babies, the objectives were to assess: (1) sensitivity and specificity of basal ganglia and thalamus (BGT) 1H MRS Lac/NAA for the prediction of Bayley III outcomes at 2 years using optimised metabolite fitting (Tarquin) with threonine and total NAA; (2) prediction of motor outcome with diffusion-weighted MRI; (3) BGT Lac/NAA correlation with the National Institute of Child Health and Human Development (NICHD) MRI score. Subjects and methods 55 (16 inborn, 39 outborn) infants at 39w+5 d (35w+5d–42w+0d) with NE admitted between February 2012 and August 2014 to University College London Hospitals for therapeutic hypothermia underwent MRI and 1H MRS at 3T on day 2–14 (median day 5). MRIs were scored. Bayley III was assessed at 24 (22–26) months. Results 16 babies died (1 inborn, 15 outborn); 20, 19 and 21 babies had poor motor, cognitive and language outcomes. Using a threshold of 0.39, sensitivity and specificity of BGT Lac/NAA for 2-year motor outcome was 100% and 97%, cognition 90% and 97% and language 81% and 97%, respectively. Sensitivity and specificity for motor outcome of mean diffusivity (threshold 0.001 mm2/s) up to day 9 was 72% and 100% and fractional anisotropy (threshold 0.198) was 39% and 94%, respectively. Lac/NAA correlated with BGT injury on NICHD scores (2A, 2B, 3). Conclusion BGT Lac/NAA on 1H MRS at 3T within 14 days accurately predicts 2-year motor, cognitive and language outcome and may be a marker directing decisions for therapies after cooling.
Overcoming challenges in variant calling: exploring sequence diversity in candidate genes for plant development in perennial ryegrass (Lolium perenne)

Abstract Revealing DNA sequence variation within the Lolium perenne genepool is important for genetic analysis and development of breeding applications. We reviewed current literature on plant development to select candidate genes in pathways that control agronomic traits, and identified 503 orthologues in L. perenne. Using targeted resequencing, we constructed a comprehensive catalogue of genomic variation for a L. perenne germplasm collection of 736 genotypes derived from current cultivars, breeding material and wild accessions. To overcome challenges of variant calling in heterogeneous outbreeding species, we used two complementary strategies to explore sequence diversity. First, four variant calling pipelines were integrated with the VariantMetaCaller to reach maximal sensitivity. Additional multiplex amplicon sequencing was used to empirically estimate an appropriate precision threshold. Second, a de novo assembly strategy was used to reconstruct divergent alleles for each gene. The advantage of this approach was illustrated by discovery of 28 novel alleles of LpSDUF247, a polymorphic gene co-segregating with the S-locus of the grass self-incompatibility system. Our approach is applicable to other genetically diverse outbreeding species. The resulting collection of functionally annotated variants can be mined for variants causing phenotypic variation, either through genetic association studies, or by selecting carriers of rare defective alleles for physiological analyses.
Baroreflex functionality in the eye of diffusion tensor imaging

By applying diffusion tensor imaging (DTI) as a physiological tool to evaluate changes in functional connectivity between key brainstem nuclei in the baroreflex neural circuits of mice and rats, recent work has revealed several hitherto unidentified phenomena regarding baroreflex functionality. (1) The presence of robust functional connectivity between nucleus tractus solitarii (NTS) and nucleus ambiguus (NA) or rostral ventrolateral medulla (RVLM) offers a holistic view on the moment‐to‐moment modus operandi of the cardiac vagal baroreflex or baroreflex‐mediated sympathetic vasomotor tone. (2) Under pathophysiological conditions (e.g. neurogenic hypertension), the disruption of functional connectivity between key nuclei in the baroreflex circuits is reversible. However, fatality ensues on progression from pathophysiological to pathological conditions (e.g. hepatic encephalopathy) when the functional connectivity between NTS and NA or RVLM is irreversibly severed. (3) The absence of functional connectivity between the NTS and caudal ventrolateral medulla (CVLM) necessitates partial rewiring of the classical neural circuit that includes CVLM as an inhibitory intermediate between the NTS and RVLM. (4) Sustained functional connectivity between the NTS and NA is responsible for the vital period between brain death and the inevitable cardiac death. (5) Reduced functional connectivity between the NTS and RVLM or NA points to inherent anomalous baroreflex functionality in floxed and Cre‐Lox mice. (6) Disrupted NTS‐NA functional connectivity in Flk‐1 (VEGFR2) deficient mice offers an explanation for the hypertensive side‐effect of anti‐vascular endothelial growth factor therapy (anti‐VEGF) therapy. These newly identified baroreflex functionalities revealed by DTI bear clinical and therapeutic implications.
Activation of the oncogenic transcription factor B-Myb via multisite phosphorylation and prolyl cis/trans isomerization

Abstract The oncogenic transcription factor B-Myb is an essential regulator of late cell cycle genes whose activation by phosphorylation is still poorly understood. We describe a stepwise phosphorylation mechanism of B-Myb, which involves sequential phosphorylations mediated by cyclin-dependent kinase (Cdk) and Polo-like kinase 1 (Plk1) and Pin1-facilitated peptidyl-prolyl cis/trans isomerization. Our data suggest a model in which initial Cdk-dependent phosphorylation of B-Myb enables subsequent Pin1 binding and Pin1-induced conformational changes of B-Myb. This, in turn, initiates further phosphorylation of Cdk-phosphosites, enabling Plk1 docking and subsequent Plk1-mediated phosphorylation of B-Myb to finally allow B-Myb to stimulate transcription of late cell cycle genes. Our observations reveal novel mechanistic hierarchies of B-Myb phosphorylation and activation and uncover regulatory principles that might also apply to other Myb family members. Strikingly, overexpression of B-Myb and of factors mediating its activation strongly correlates with adverse prognoses for tumor patients, emphasizing B-Myb's role in tumorigenesis.
Endovascular treatment of femoro‐popliteal lesions

Peripheral artery disease (PAD) is a major health concern affecting more than 200 million people worldwide and studies have shown PAD to be a strong predictor of mortality, morbidity, and disability. The management of PAD is multi‐tiered and advancements in technology have given physicians more options for endovascular revascularization if medical therapy does not result in substantial improvement. Many randomized controlled trials have reported efficacy of various therapies including laser atherectomy, stent technology, and drug‐coated balloons over standard percutaneous transluminal angioplasty; however, uncertainty regarding the best standard of care remains unclear because of a lack of head to head comparisons between novel therapies. Furthermore, variability in the reported clinical outcomes exists and makes it difficult to evaluate the superiority of any specific treatment modality, especially for functional capacity and quality of life. Recently established consensus definitions for clinical outcomes coupled with investigators incorporating direct comparisons within clinical trials will be crucial to establish consistent care and meaningful gain in treatment for these patients. This review will highlight the treatment modalities, literature supporting each treatment modality, and insight into why they are being used and why variation exists around the United States.
Targeting peptide‐enhanced antibody and CD11c+ dendritic cells to inclusion bodies expressing protective antigen against ETEC in mice

Enterotoxigenic Escherichia coli (ETEC) remains a massive burden in developing countries with increasing morbidity and mortality rates; it is also an important pathogen in the farming industry and is a leading cause of bacterial diarrhea. Our previous study showed that nanometer‐sized inclusion bodies (IBs) of the fimbrial adhesin subunit protein (FaeG), mutation heat‐stable enterotoxin a (mSTa), heat‐labile enterotoxin b (LTb), and STb (nontargeting) fusion protein as an oral vaccine induced both systemic and mucosal immune responses. In this study, to enhance the protective efficacy to ETEC, we used Yersinia enterocolitica adhesive and M‐cell‐targeting peptides to analyze high‐efficiency antigen‐specific immune presentation in the gut. Here, we showed that immunization with the IBs of ETEC—FaeG‐mSTa‐LTb‐STb—induced a specific systemic and mucosal immune response in the gut, whereas the combination of both targeting peptides resulted in the highest titer, protective immune response against ETEC. A lymphocyte proliferation assay has shown that the IBs induced immunologic memory. The specific antibody of the targeting groups could effectively neutralize toxins, thereby protecting the cells of the small intestine and reducing the level of cAMP and cGMP, and the groups with double targeting showed the best effect. The most important finding was that the targeting peptides stimulate the T helper (Th) cells through Th17 and Thl and that Thl cells dominated the cellular immune response. We found that the targeting peptide could also activate CD11c+ on lymphoid dendritic cells, which processed and presented antigens to T cells through Th1‐mediated IFN‐γ and IL‐12, thereby enhancing the antibody titers. The double‐targeting peptide had a better effect on stimulating the immune cells to enhance the antibody titers. —Jiang, X. , Xia, S. , He, X. , Ma, H. , Feng, Y. , Liu, Z. , Wang, W. , Tian, M. , Chen, H. , Peng, F. , Wang, L. , Zhao, P., Ge, J., Liu, D. Targeting peptide‐enhanced antibody and CD11c+ dendritic cells to inclusion bodies expressing protective antigen against ETEC in mice. FASEB J. 33, 2836–2847 (2019). www.fasebj. org
The effect of low-level laser therapy and physical exercise on pain, stiffness, function, and spatiotemporal gait variables in subjects with bilateral knee osteoarthritis: a blind randomized clinical trial

Abstract Objective: To evaluate the effects of individual and combination therapies (low-level laser therapy and physical exercises) on pain, stiffness, function, and spatiotemporal gait variables in subjects with bilateral knee osteoarthritis (OA). Methods: Subjects with knee OA (Grades 1–3) were evaluated and randomized into four groups: Control Group (CG), untreated; Laser Group (LG), treated with laser at 808 nm, 5.6 J; Exercise Group (EG), treated with exercise; and Laser + Exercise Group (LEG), treated with laser and exercises. The treatment was carried out twice a week for 2 months. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire was applied for evaluation and reevaluation; evaluation of spatiotemporal gait variables was performed using GAITRite equipment. Results: The EG showed significant improvement in pain (p = 0.006) and function (p = 0.01) according to WOMAC. Regarding gait variables, in intergroup analysis after 8 weeks all groups receiving intervention showed a significant increase in gait speed: LG versus CG (p = 0.03); EG versus CG (p = 0.04) and LEG versus CG (p = 0.005). Only the group treated with laser + exercise showed a significant increase (p = 0.009) in the cadence and duration of single right limb support (p = 0.04), and only the groups treated with exercise and laser + exercise showed significant decreases in the duration of right limb support (p = 0.035 and p = 0.003, respectively), compared to the CG. Conclusions: The group treated only with exercise showed improvement in WOMAC questionnaire scores. Regarding the gait variables, all groups undergoing the interventions showed increases in the gait speed compared to the CG. The laser and exercise combination therapy provided the best results for the other gait variables (cadence and duration of right limb support and duration of single right limb support). Implications for rehabilitation There are differences in gait patterns in patients with knee OA, including decreased gait speed, cadence, and step length. The results shown in the present study provide additional information about the physical therapy approaches that should be chosen during clinical practical to improve gait performance in individuals with knee osteoarthritis. The improvement in gait performance is a relevant issue due to the fact that is associated to physical independence and better quality of life.