Miracle-dz/UniFAR-FTUs huggingface dataset:
Reconstitution of 3′ end processing of mammalian pre-mRNA reveals a central role of RBBP6

Here, Schmidt et al. reconstituted the endonucleolytic cleavage of an extended precursor followed by the addition of a poly(A) tail reaction from overproduced and purified proteins, and provide a minimal list of 14 polypeptides that are essential and two that are stimulatory for RNA processing.
Handgrip strength asymmetry is associated with the risk of neurodegenerative disorders among Chinese older adults

Neurodegenerative disorders, as the irreversible condition, have a long, silent preclinical period. Recognition of early physical signs of neurodegenerative disorders had important practical implications for identifying at‐risk population. The aim of this study was to investigate whether handgrip strength (HGS) asymmetry was associated with the incidence of neurodegenerative disorders among Chinese older adults.
Assessment of A1 and A2 variants in the CNS2 gene of some cattle breeds by using ACRS-PCR method

Abstract The aim of this study is to reveal β-casein polymorphism of some cattle breeds and also the potential to produce A2 milk from existing animals and to develop strategies in this area. Therefore, a total of 400 cattle, 100 animals from each breed of Holstein, Brown Swiss, Jersey and Simmental raised commonly in Turkey, were obtained, and C > A polymorphism in 67th amino acid in the 7th exons of β-casein gene was determined by TaqI enzyme with PCR-ACRS method. Blood samples were collected from dairy cattle farms raising Holstein, Brown Swiss and Jersey breeds from Konya province and Simmental breed from Kütahya province in Turkey. A1 and A2 allele frequencies in Holstein, Brown Swiss, Jersey and Simmental cattle breeds were determined as 0.475/0.525, 0.370/0.630, 0.215/0.785 and 0.440/0.560, respectively. The highest A2 allele frequency (0.785) was found in Jersey breed. A1A1 genotypes in Holstein, Brown Swiss, Jersey and Simmental breeds were 0.240, 0.150, 0.030 and 0.160, respectively; A1A2 genotypes were 0.470, 0.440, 0.370 and 0.560, respectively; A2A2 genotypes were determined as 0.290, 0.410, 0.600 and 0.280, respectively. In these breeds, the highest A2A2 genotype frequency was found in Jersey (0.600), the lowest A1A1 genotype frequency (0.030) was found in Jersey and the highest A1A2 genotype frequency (0.560) was found in Simmental. Holstein, Brown Swiss, Simmental and Jersey populations were at the level of Hardy-Weinberg in terms of β-casein gene (p > 0.05). The average Ho, He and PIC values were calculated as 0.460, 0.469 and 0.605, respectively. In conclusion, the frequency of commonly reared cattles in Turkey especially Brown Swiss, and Jersey breeds in A2A2 genotype are satisfactory, but it can be said that the use of animals with A2 allele in selection is extremely important for increasing A2 milk producing potential in the future.
A review on hydroxy anthraquinones from bacteria: crosstalk’s of structures and biological activities

Abstract Anthraquinones (AQ), unveiling large structural diversity, among polyketides demonstrate a wide range of applications. The hydroxy anthraquinones (HAQ), a group of anthraquinone derivatives, are secondary metabolites produced by bacteria and eukaryotes. Plant-based HAQ are well–studied unlike bacterial HAQ and applied as herbal medicine for centuries. Bacteria are known to synthesize a wide variety of structurally diversified HAQ through polyketide pathways using polyketide synthases (I, II & III) principally through polyketide synthase-II. The actinobacteria especially the genus Streptomyces and Micromonospora represent a rich source of HAQ, however novel HAQ are reported from the rare actinobacteria genera (Salinospora, Actinoplanes, Amycoloptosis, Verrucosispora, Xenorhabdus, and Photorhabdus. Though several reviews are available on AQ produced by plants and fungi, however none on bacterial AQ. The current review focused on sources of bacterial HAQ and their structural diversity and biological activities along with toxicity and side effects. Graphical Abstract
Restoration of Autophagic Flux Improves Endothelial Function in Diabetes Through Lowering Mitochondrial ROS-mediated eNOS Monomerization.

Endothelial nitric oxide synthase (eNOS) monomerization and uncoupling play crucial roles in mediating vascular dysfunction in diabetes mellitus although the underlying mechanisms are still incompletely understood. Growing evidence indicates that autophagic dysregulation is involved in the pathogenesis of diabetic endothelial dysfunction, however, whether autophagy regulates eNOS activity through controlling eNOS monomerization/dimerization remains elusive. The present study shows that autophagic flux was impaired in the endothelium of diabetic db/db mice and in human endothelial cells exposed to advanced glycation end products or oxidized low-density lipoprotein. Inhibition of autophagic flux by chloroquine or bafilomycin A1 were sufficient to induce eNOS monomerization and lowers nitric oxide bioavailability through raising mitochondrial reactive oxygen species (mtROS). Restoration of autophagic flux by overexpressing transcription factor EB (TFEB), a master regulator of autophagy and lysosomal biogenesis, decreased endothelial cell oxidative stress, increased eNOS dimerization and improved endothelium-dependent relaxations (EDR) in db/db mouse aortas. Inhibition of mammalian target of rapamycin kinase (mTOR) increased TFEB nuclear localization, reduced mtROS accumulation, facilitated eNOS dimerization, and enhanced EDR in db/db mice. Moreover, calorie restriction also elevated TFEB expression, improved autophagic flux, and restored EDR in the aortas of db/db mice. Taken together, the present study reveals that mtROS-induced eNOS monomerization is closely associated with the impaired TFEB-autophagic flux axis leading to endothelial dysfunction in diabetic mice.
Gut-oriented interventions in patients with multiple sclerosis: fact or fiction?

OBJECTIVE Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, disimmune disease of the central nervous system whose etiology and pathogenesis remain poorly understood, due to its complex and multifactorial nature. Evidence of a bidirectional connection linking the gut microbiome with the intestinal barrier and the immune system (the gut-brain axis) may have implications for the pathogenesis of inflammatory demyelinating diseases such as MS. This narrative review summarizes the evidence for the gut-brain axis involvement in the pathogenesis of MS and examines the role of gut-oriented interventions in MS. PATIENTS AND METHODS We reviewed all available studies in PubMed concerning gut-directed interventions and MS. This research was conducted using different combinations of pertinent keywords (multiple sclerosis, immune-mediated inflammatory diseases, autoimmune diseases, first demyelinating event, neurocognition, neurological disorders, neurology practice, risk factors, taxonomic biomarkers, nutrition, diet, dietary additives, complementary treatment, gut bacteria, gut microbiome, microbiome, gut-brain axis, epidemiology, alpha-linolenic acid, fermentative metabolites, fat, saturated fat, monounsaturated fat, polyunsaturated fat, omega-3 fatty acids, calorie restricted diet, fasting, fecal microbiome, fecal microbiota transplantation, animal testing). RESULTS There is an emerging evidence that alterations in the gut microbiome and increased intestinal permeability may be causative factors in the complex interplay between nutrition, metabolic status and the immune-inflammatory response in patients with MS. This suggests the possibility that modification of lifestyle and the microbiome, for example by specific diets or fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers, may positively influence the pathogenesis of MS. CONCLUSIONS Although the role of nutritional factors in the pathogenesis of MS remains to be established, there is evidence that appropriate gut-directed interventions such as diet, nutritional supplementation or fecal transplantation may modulate the inflammatory response and improve the course of MS as a complementary treatment in the disease.
epiGBS2: Improvements and evaluation of highly multiplexed, epiGBS‐based reduced representation bisulfite sequencing

Several reduced‐representation bisulfite sequencing methods have been developed in recent years to determine cytosine methylation de novo in nonmodel species. Here, we present epiGBS2, a laboratory protocol based on epiGBS with a revised and user‐friendly bioinformatics pipeline for a wide range of species with or without a reference genome. epiGBS2 is cost‐ and time‐efficient and the computational workflow is designed in a user‐friendly and reproducible manner. The library protocol allows a flexible choice of restriction enzymes and a double digest. The bioinformatics pipeline was integrated in the Snakemake workflow management system, which makes the pipeline easy to execute and modular, and parameter settings for important computational steps flexible. We implemented bismark for alignment and methylation analysis and we preprocessed alignment files by double masking to enable single nucleotide polymorphism calling with Freebayes (epiFreebayes). The performance of several critical steps in epiGBS2 was evaluated against baseline data sets from Arabidopsis thaliana and great tit (Parus major), which confirmed its overall good performance. We provide a detailed description of the laboratory protocol and an extensive manual of the bioinformatics pipeline, which is publicly accessible on github (https://github.com/nioo‐knaw/epiGBS2) and zenodo (https://doi.org/10.5281/zenodo.4764652).
Fast Photoneutron Detection

The purpose of this project was to investigate fast photoneutron production from a series of materials commonly used for backing neutron beam guides. Fast neutrons were knocked out of these materials by exposing them to to high-energy photons at the Tagged-Photon Facility at MAX-lab in Lund, Sweden. Liquid scintillator detectors at different angles around the targets registered the photoknockout neutrons. These fast-neutron detectors were energy calibrated using two well-understood gamma-ray sources. The energy calibrations were used to establish the hardware detector thresh- olds. The hardware thresholds server as input to an absolute neutron-detection efficiency Monte Carlo simulation known as STANTON, which was used to establish the best-case neutron-detection efficiency achieved in the measurement. Finally, the detector thresh- olds were increased in software to study the reduction in detection efficiency as a function of the increase in threshold. A complete overview of the project is presented.
Cardiomyocyte stromal interaction molecule 1 is a key regulator of Ca2+‐dependent kinase and phosphatase activity in the mouse heart

Stromal interaction molecule 1 (STIM1) is a major regulator of store‐operated calcium entry in non‐excitable cells. Recent studies have suggested that STIM1 plays a role in pathological hypertrophy; however, the physiological role of STIM1 in the heart is not well understood. We have shown that mice with a cardiomyocyte deletion of STIM1 (crSTIM1−/−) develop ER stress, mitochondrial, and metabolic abnormalities, and dilated cardiomyopathy. However, the specific signaling pathways and kinases regulated by STIM1 are largely unknown. Therefore, we used a discovery‐based kinomics approach to identify kinases differentially regulated by STIM1. Twelve‐week male control and crSTIM1−/− mice were injected with saline or phenylephrine (PE, 15 mg/kg, s.c, 15 min), and hearts obtained for analysis of the Serine/threonine kinome. Primary analysis was performed using BioNavigator 6.0 (PamGene), using scoring from the Kinexus PhosphoNET database and GeneGo network modeling, and confirmed using standard immunoblotting. Kinomics revealed significantly lower PKG and protein kinase C (PKC) signaling in the hearts of the crSTIM1−/− in comparison to control hearts, confirmed by immunoblotting for the calcium‐dependent PKC isoform PKCα and its downstream target MARCKS. Similar reductions in crSTIM1−/− hearts were found for the kinases: MEK1/2, AMPK, and PDPK1, and in the activity of the Ca2+‐dependent phosphatase, calcineurin. Electrocardiogram analysis also revealed that crSTIM1−/− mice have significantly lower HR and prolonged QT interval. In conclusion, we have shown several calcium‐dependent kinases and phosphatases are regulated by STIM1 in the adult mouse heart. This has important implications in understanding how STIM1 contributes to the regulation of cardiac physiology and pathophysiology.
LPV model reduction of UAV lateral system

Unmanned aerial vehicle(UAV) linear parameter-varying(LPV) models can capture the possible nonlinear dynamics.When pursuing an LPV formulation,one ends up with models of relatively large dimension.Accordingly,finding control syntheses usually requires substantial computation.Therefore,an LPV model reduction theory based on balanced truncation method is proposed.First,the concepts of well-posedness,stability and balanced realizations in a linear fractional transformation framework are given.Then a generalization of the balanced truncation procedure for the LPV model reduction is presented.Finally,LPV model is built with linear time-invariable(LTI) models of UAV lateral system by polynomial fitting.The proposed method is applied to reduce the lateral system LPV model.Simulation results show that the step response of the reduced-order model meets the accuracy specification of output response.
Botulinum Toxin A in the Management of Pediatric Sialorrhea: A Systematic Review

Objective: Botulinum toxin A is known to be effective and safe in managing sialorrhea in pediatric patients; however, there is no consensus on a protocol for optimal injection sites and appropriate dosing for injection. Methods: This review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol. PubMed, EMBASE, and other databases were queried to identify articles that evaluated botulinum toxin type A for the treatment of sialorrhea in the pediatric population. A total of 405 studies were identified. After applying inclusion and exclusion criteria, 31 articles were included for review. Results: A total of 14 studies evaluated 2-gland injections, and 17 studies evaluated 4-gland injections. Of the 31 studies included, one study assessed incobotulinumtoxinA (Xeomin®) the remaining all used onabotulinumtoxinA (Botox®). For 2-gland injection studies, a combined total of 899 participants were reviewed, where 602 participants received 50 units into their submandibular glands, while 262 participants received 30 to 50 units. Among 4-gland injection studies, there was a combined total of 388 participants, with the most prevalent dosage utilized being 60 to 100 units in 230 participants, followed by 100 units total in 77 participants. The most common adverse event was dysphagia which resolved in nearly all cases. Three studies aimed to examine 2-gland versus 4-gland injections, with 2 of the studies concluding 4-gland injection was superior. Conclusions: The strength of evidence suggests that the dosing of 50 units total of onabotulinumtoxinA to the submandibular glands is safe and effective in the pediatric population. For 4-gland injections, bilateral submandibular and parotid gland injections of 60 to 100 units total is the safe and effective dosage. There is no substantial evidence comparing 4-gland injections to 2-gland injections, but research thus far suggests 4-gland injections to be superior. Future study is needed to evaluate incobotulinumtoxinA and abobotulinumtoxinA dosages in the pediatric population.
Short-Range Structural Connections Are More Severely Damaged in Early-Stage MS

The authors demonstrate that more severe demyelination preceding axonal degeneration occurs in short-range connections but not in long-range connections in early-stage MS, suggesting the possibility that there are cortical lesions that are undetectable by current MR imaging. BACKGROUND AND PURPOSE: Long-range connections are more severely damaged and relevant for cognition in long-standing MS. However, the evolution of such coordinated network damage in patients with MS is unclear. We investigated whether short- and long-range structural connections sustained equal damage in early-stage MS. MATERIALS AND METHODS: Sixteen patients with early-stage MS and 17 healthy controls were scanned by high-resolution, multishell diffusion imaging on 7T MR imaging and assessed cognitively. We investigated macrostructural properties in short- and long-range fibers and of microstructural metrics derived from 2 quantitative diffusion MR imaging models: DTI and neurite orientation dispersion and density imaging. RESULTS: Patients had significant WM integrity damage—that is, higher radial diffusivity and a lower intracellular volume fraction in the focal WM lesions. Compared with the healthy controls, the patients had noticeable microstructure changes in both short- and long-range fibers, including increased radial diffusivity, mean diffusivity, and axial diffusivity. Z scores further indicated greater damage in the short-range fibers than in the long-range fibers. CONCLUSIONS: Our findings demonstrate that more severe demyelination preceding axonal degeneration occurs in short-range connections but not in long-range connections in early-stage MS, suggesting the possibility that there are cortical lesions that are undetectable by current MR imaging.
Connecting Real IP Value To Business Strategy

The paper begins with the hypothesis that current citation-based and classification code based patent search techniques offer little if any value to organizations in terms of either locating disruptive threats or opportunities, or providing leaders with forward looking strategic information. The paper goes on to discuss how the findings of the three-million data-point TRIZ/Systematic Innovation research have uncovered findings capable of addressing a forward-looking, predictive search and analysis capability that allows inventors and problem solvers to assess the likely value of a patent application before it is filed.
Effects of Stimulus Polarity on Amplitude-Modulated Cervical Vestibular-Evoked Myogenic Potentials.

BACKGROUND Traditional approaches to cervical vestibular-evoked myogenic potentials use a transient stimulus to elicit an onset response. However, alternate approaches with long duration stimuli may allow the development of new methodologies to better understand basic function of the vestibular system, as well as potentially developing new clinical applications. PURPOSE The objective of this study was to examine the effects of stimulus polarity on response properties of amplitude-modulated cervical vestibular-evoked myogenic potentials (AMcVEMPs). RESEARCH DESIGN Prospective, repeated-measures, within-subjects design. STUDY SAMPLE Participants were 16 young, healthy adults (ages 21-38 years). DATA COLLECTION AND ANALYSIS Amplitude-modulated tones, with carrier frequency of 500 Hz and modulation frequency of 37 Hz, were used to elicit AMcVEMPs. Responses were analyzed in three different stimulus polarity conditions: condensation, rarefaction, and alternating. The resulting data were analyzed for differences across polarity conditions. RESULTS AMcVEMP amplitudes, both raw and corrected for tonic muscle activation, were equivalent across the different stimulus phase conditions. In addition, response signal-to-noise ratio and phase coherence were equivalent across the different phases of the stimulus. CONCLUSION Analyses of AMcVEMPs are stable when the carrier frequency starting phase is altered and the phase of the temporal envelope is constant.
Feasibility of discharge within 72 hours of major colorectal surgery: lessons learned after 5 years of institutional experience with the ERAS protocol

Abstract Background Early postoperative discharge after colorectal surgery within the enhanced recovery after surgery (ERAS) guidelines has been demonstrated to be safe, although its applicability has not been universal. The primary aim of this study was to identify the predictors of early discharge and readiness for discharge in a study population. Methods Early discharge was defined as discharge occurring in 72 h or less after surgery. The characteristics and clinical outcomes of the patients in the early and non-early discharge groups were compared, and variables associated with early discharge were identified. Additionally, independent variables associated with the readiness for discharge within 48 h were evaluated. Results Of 965 patients who underwent colorectal surgery between January 2015 and July 2020, 788 were included in this study. No differences in readmission, reoperation, or 30-day mortality were observed between the early and non-early discharge groups. Both early discharge and readiness for discharge had a positive association with adherence to 80 per cent or more of the ERAS items and a negative association with the female sex, duration of surgery, drain positioning, and postoperative complications. Conclusion Early discharge after colorectal surgery is safe and feasible, and is not associated with a high risk of readmission or reoperation. Discharge at 48 h can be reliably predicted in a subset of patients. Future studies should collect prospective data on early discharge related to safety, as well as patients’ expectations, possible organizational issues, and effective costs reduction in Italian clinical practice.
Selection of reference genes for quantitative analysis of microRNA expression in three different types of cancer

MicroRNAs (miRNAs) are promising biomarkers in cancer research. Quantitative PCR (qPCR), also known as real-time PCR, is the most frequently used technique for measuring miRNA expression levels. The use of this technique, however, requires that expression data be normalized against reference genes. The problem is that a universal internal control for quantitative analysis of miRNA expression by qPCR has yet to be known. The aim of this work was to find the miRNAs with stable expression in the thyroid gland, brain and bone marrow according to NanoString nCounter miRNA quantification data. As a results, the most stably expressed miRNAs were as follows: miR-361-3p, -151a-3p and -29b-3p in the thyroid gland; miR-15a-5p, -194-5p and -532-5p in the brain; miR-140-5p, -148b-3p and -362-5p in bone marrow; and miR-423-5p, -28-5p and -532-5p, no matter what tissue type. These miRNAs represent promising reference genes for miRNA quantification by qPCR.
Status of Large Diameter SiC Single Crystals

Large-diameter SiC single crystals are grown at II-VI by the sublimation technique. 100mm substrates of semi-insulating 6H SiC and n-type 4H SiC are produced as commercial products; in development, diameter expansion to 125mm has been achieved. Over the last two years, significant improvements have been made in crystal quality. The values of FWHM of x-ray rocking curves are typically 20-40 arc-seconds for 6H SI wafers and 12-30 arc-seconds for 4H n+ wafers. Micropipe density is less than 3 cm-2, and less than 0.1 cm-2 in best substrates. Electrical resistivity of SI substrates is, typically, of 1011 Ω•cm or above. For 4H n+ substrates, the typical dislocation density is about 9×103 cm-2 and the typical BPD density is less than 1×103 cm-2.