Miracle-dz/UniFAR-FTUs huggingface dataset:
Human cerebrospinal fluid promotes spontaneous gamma oscillations in the hippocampus in vitro

Gamma oscillations (30–80 Hz) are fast network activity patterns frequently linked to cognition. They are commonly studied in hippocampal brain slices in vitro, where they can be evoked via pharmacological activation of various receptor families. One limitation of this approach is that neuronal activity is studied in a highly artificial extracellular fluid environment, as provided by artificial cerebrospinal fluid (aCSF). Here, we examine the influence of human cerebrospinal fluid (hCSF) on kainate‐evoked and spontaneous gamma oscillations in mouse hippocampus. We show that hCSF, as compared to aCSF of matched electrolyte and glucose composition, increases the power of kainate‐evoked gamma oscillations and induces spontaneous gamma activity in areas CA3 and CA1 that is reversed by washout. Bath application of atropine entirely abolished hCSF‐induced gamma oscillations, indicating critical contribution from muscarinic acetylcholine receptor‐mediated signaling. In separate whole‐cell patch clamp recordings from rat hippocampus, hCSF increased theta resonance frequency and strength in pyramidal cells along with enhancement of h‐current (Ih) amplitude. We found no evidence of intrinsic gamma frequency resonance at baseline (aCSF) among fast‐spiking interneurons, and this was not altered by hCSF. However, hCSF increased the excitability of fast‐spiking interneurons, which likely contributed to gamma rhythmogenesis. Our findings show that hCSF promotes network gamma oscillations in the hippocampus in vitro and suggest that neuromodulators distributed in CSF could have significant influence on neuronal network activity in vivo.
Demonstration of a Low-Cost Multi-Pollutant Network to Quantify Intra-Urban Spatial Variations in Air Pollutant Source Impacts and to Evaluate Environmental Justice

Air quality monitoring has traditionally been conducted using sparsely distributed, expensive reference monitors. To understand variations in PM2.5 on a finely resolved spatiotemporal scale a dense network of over 40 low-cost monitors was deployed throughout and around Pittsburgh, Pennsylvania, USA. Monitor locations covered a wide range of site types with varying traffic and restaurant density, varying influences from local sources, and varying socioeconomic (environmental justice, EJ) characteristics. Variability between and within site groupings was observed. Concentrations were higher near the source-influenced sites than the Urban or Suburban Residential sites. Gaseous pollutants (NO2 and SO2) were used to differentiate between traffic (higher NO2 concentrations) and industrial (higher SO2 concentrations) sources of PM2.5. Statistical analysis proved these differences to be significant (coefficient of divergence > 0.2). The highest mean PM2.5 concentrations were measured downwind (east) of the two industrial facilities while background level PM2.5 concentrations were measured at similar distances upwind (west) of the point sources. Socioeconomic factors, including the fraction of non-white population and fraction of population living under the poverty line, were not correlated with increases in PM2.5 or NO2 concentration. The analysis conducted here highlights differences in PM2.5 concentration within site groupings that have similar land use thus demonstrating the utility of a dense sensor network. Our network captures temporospatial pollutant patterns that sparse regulatory networks cannot.
The draft genome of a wild barley genotype reveals its enrichment in genes related to biotic and abiotic stresses compared to cultivated barley

Summary Wild barley (Hordeum spontaneum) is the progenitor of cultivated barley (Hordeum vulgare) and provides a rich source of genetic variations for barley improvement. Currently, the genome sequences of wild barley and its differences with cultivated barley remain unclear. In this study, we report a high‐quality draft assembly of wild barley accession (AWCS276; henceforth named as WB1), which consists of 4.28 Gb genome and 36 395 high‐confidence protein‐coding genes. BUSCO analysis revealed that the assembly included full lengths of 95.3% of the 956 single‐copy plant genes, illustrating that the gene‐containing regions have been well assembled. By comparing with the genome of the cultivated genotype Morex, it is inferred that the WB1 genome contains more genes involved in resistance and tolerance to biotic and abiotic stresses. The presence of the numerous WB1‐specific genes indicates that, in addition to enhance allele diversity for genes already existing in the cultigen, exploiting the wild barley taxon in breeding should also allow the incorporation of novel genes. Furthermore, high levels of genetic variation in the pericentromeric regions were detected in chromosomes 3H and 5H between the wild and cultivated genotypes, which may be the results of domestication. This H. spontaneum draft genome assembly will help to accelerate wild barley research and be an invaluable resource for barley improvement and comparative genomics research.
Overproduction of endothelin-1 impairs glucose tolerance but does not promote visceral adipose tissue inflammation or limit metabolic adaptations to exercise.

Endothelin-1 (ET-1) is a potent vasoconstrictor and proinflammatory peptide that is upregulated in obesity. Herein, we tested the hypothesis that ET-1 signaling promotes visceral adipose tissue (AT) inflammation and disrupts glucose homeostasis. We also tested if reduced ET-1 is a required mechanism by which exercise ameliorates AT inflammation and improves glycemic control in obesity. We found that (i) diet-induced obesity, AT inflammation, and glycemic dysregulation were not accompanied by significant increased levels of ET-1 in AT or circulation in wild-type mice; and that endothelial overexpression of ET-1 and consequent increased ET-1 levels did not cause AT inflammation yet impaired glucose tolerance; (ii) reduced AT inflammation and improved glucose tolerance with voluntary wheel running was not associated with decreased levels of ET-1 in AT or circulation in obese mice, nor did endothelial overexpression of ET-1 impede such exercise-induced metabolic adaptations; (iii) chronic pharmacological blockade of ET-1 receptors did not suppress AT inflammation in obese mice but improved glucose tolerance; and (iv) in a cohort of human subjects with a wide range of BMI, ET-1 levels in AT or circulation were not correlated with markers of inflammation in AT. In aggregate, we conclude that ET-1 signaling is not implicated in the development of visceral AT inflammation but promotes glucose intolerance, thus representing an important therapeutic target for glycemic dysregulation in conditions characterized by hyperendothelinemia. Furthermore, we show that the salutary effects of exercise on AT and systemic metabolic function are not contingent on the suppression of ET-1 signaling.
Novel mRNAs 3′ end-associated cis-regulatory elements with epigenomic signatures of mammalian enhancers in the Arabidopsis genome

The precise spatial and temporal control of gene expression requires the coordinated action of genomic cis-regulatory elements (CREs), including transcriptional enhancers. However, our knowledge of enhancers in plants remains rudimentary and only a few plant enhancers have been experimentally defined. Here, we screened the Arabidopsis thaliana genome and identified >1900 unique candidate CREs that carry the genomic signatures of mammalian enhancers. These were termed putative enhancer-like elements (PEs). Nearly all PEs are intragenic and, unexpectedly, most associate with the 3′ ends of protein-coding genes. PEs are hotspots for transcription factor binding and harbor motifs resembling cleavage/polyadenylation signals, potentially coupling 3′ end processing to the transcriptional regulation of other genes. Hi-C data showed that 24% of PEs are located at regions that can interact intrachromosomally with other protein-coding genes and, surprisingly, many of these target genes interact with PEs through their 3′ UTRs. Examination of the genomes of 1135 sequenced Arabidopsis accessions showed that PEs are conserved. Our findings suggest that the identified PEs may serve as transcriptional enhancers and sites for mRNA 3′ end processing, and constitute a novel group of CREs in Arabidopsis.
Individualized, Single Session Yoga Therapy to Reduce Physical and Emotional Symptoms in Hospitalized Hematological Cancer Patients

Objective: Inpatient treatment of hematological cancer is among the most physically and mentally arduous cancer treatments, and it is associated with a number of common physical, emotional, and social symptoms that can negatively affect quality of life (QOL) for years following treatment. While treating symptoms during hospitalization holds promise for improving long-term QOL, successful approaches likely require multidisciplinary interventions. In this article, we describe a 4-year effort in program enhancement that incorporated an adjunctive single yoga therapy session during treatment for hematological malignancies. Methods: Hospitalized patients receiving treatment for hematological cancer (N = 486) were provided a 40-minute individualized yoga therapy session. We evaluated feasibility and acceptance by quantifying the percentage of patients who discontinued the yoga session due to pain, discomfort, or another reason, and by comparing the intervention population to the demographic makeup of the unit more generally. Patient-reported symptoms were obtained before and after each session, and we evaluated acute symptom change for the entire sample and in subsamples that are less likely to use mindfulness-based interventions such as yoga. Results: The majority of sessions (87%) were completed, and the majority of unfinished sessions were interrupted by a medical procedure or because the patient fell asleep. No session was stopped early due to patients’ reported pain. Significant decreases were reported in all symptoms, with the greatest decrease in fatigue and anxiety. Conclusions: Yoga therapy was a feasible and effective nondrug adjunct intervention for hospitalized patients receiving treatment for hematological cancer, including bone marrow transplantation.
Decellularised baby spinach leaves and their potential use in tissue engineering applications: Studying and promoting neovascularisation

Although significant progress has been made, delayed neovascularisation of tissue-engineered constructs still remains challenging for the survival of constructs post-grafting. The addition of laboratory expanded proangiogenic cells to tissue engineering scaffold systems prior to implantation is a promising approach to overcome the slow neovascularisation. The use of decellularised biological constructs is an emerging strategy for producing physiologically relevant scaffolds for use in both pre-clinical and clinical applications. Decellularised plant architectures have recently been proposed as one approach – here we seek to confirm and extend this work by preparing baby spinach leaves without damaging their intrinsic vascular architecture and to explore their efficacy once seeded with cells to promote neovascularisation in a chick bioassay of neovascularisation. Firstly, the in vitro biocompatibility of the decellularised spinach leaves and the effect of gelatin coating on cell attachment and proliferation were assessed. The decellularised leaves showed no toxicity to cells, and gelatin coating and the presence of fibroblasts enhanced the survival of human endothelial cells in the scaffolds. The proangiogenic activity of these cell populated scaffolds was then investigated in ex ovo chick chorioallantoic membrane assay where the presence of the endothelial cells significantly promoted angiogenesis over seven days. In conclusion, these results support a small but growing body of literature that suggests the use of decellularised plants as potential scaffolds to promote neovascularisation for tissue engineering constructs.
The nuclear concentration required for antisense oligonucleotide activity in myotonic dystrophy cells

Antisense oligonucleotides (ASOs) are a promising class of therapeutics that are starting to emerge in the clinic. Determination of intracellular concentrations required for biologic effects and identification of effective delivery vehicles are crucial for understanding the mode of action and required dosing. Here, we investigated which nuclear oligonucleotide concentration is needed for a therapeutic effect for a triplet repeat‐targeting ASO in a muscle cell model of myotonic dystrophy type 1 (DM1). For cellular delivery, ASOs were complexed into nanoparticles using the cationic cell‐penetrating peptides nona‐arginine and PepFect14 (PF14). Although both peptides facilitated uptake, only PF14 led to a dose‐dependent correction of disease‐typical abnormal splicing. In line with this observation, time‐lapse confocal microscopy demonstrated that only PF14 mediated translocation of the ASOs to the nucleus, which is the main site of action. Through fluorescence lifetime imaging, we could distinguish intact oligonucleotide from free fluorophore, showing that PF14 also shielded the ASOs from degradation. Finally, we employed a combination of live‐cell fluorescence correlation spectroscopy and immunofluorescence microscopy and demonstrated that intranuclear blocking—type oligonucleotide concentrations in the upper nanomolar range were required to dissolve nuclear muscleblind‐like protein 1 foci, a hallmark of DM1. Our findings have important implications for the clinical use of ASOs in DM1 and provide a basis for further research on other types of ASOs. —Van der Bent, M. L. , Paulino da Silva Filho, O. , Willemse, M. , Hällbrink, M. , Wansink, D. G. , Brock, R. The nuclear concentration required for antisense oligonucleotide activity in myotonic dystrophy cells. FASEB J. 33, 11314–11325 (2019). www.fasebj. org
Inkjet Printing of Polyacrylic Acid-Coated Silver Nanoparticle Ink onto Paper with Sub-100 Micron Pixel Size

Printed electronics (PE) technology shows huge promise for the realisation of low-cost and flexible electronics, with the ability to pattern heat- or pressure-sensitive materials. In future developments of the PE market, the ability to produce highly conductive, high-resolution patterns using low-cost and roll-to-roll processes, such as inkjet printing, is a critical technology component for the fabrication of printed electronics and displays. Here, we demonstrate inkjet printing of polyacrylic acid (PAA) capped silver nanoparticle dispersions onto paper for high-conductivity electronic interconnects. We characterise the resulting print quality, feature geometry and electrical performance of inkjet patterned features and demonstrate the high-resolution printing, sub-100 micron feature size, of silver nanoparticle materials onto flexible paper substrate. Printed onto photo-paper, these materials then undergo chemically triggered sintering on exposure to chloride contained in the paper. We investigated the effect of substrate temperature on the properties of printed silver material from room temperature to 50 °C. At room temperature, the resistivity of single layer printed features, of average thickness of 500 nm and width 85 µm, was found to be 2.17 × 10−7 Ω·m or 13 times resistivity of bulk silver (RBS). The resistivity initially decreased with an increase in material thickness, when achieved by overprinting successive layers or by decreasing print pitch, and a resistivity of around 10 times RBS was observed after overprinting two times at pitch 75 µm and with single pass print pitch of between 60 and 80 µm, resulting in line thickness up to 920 nm. On further increases in thickness the resistivity increased and reached 27 times RBS at print pitch of 15 µm. On moderate heating of the substrate to 50 °C, more compact silver nanoparticle films were formed, reducing thickness to 200 nm from a single pass print, and lower material resistivity approaching five times RBS was achieved.
Linkage mapping an indoxacarb resistance locus in Helicoverpa armigera (Lepidoptera: Noctuidae) by genotype-by-sequencing.

BACKGROUND A major challenge to sustainable agricultural pest control is the rapid evolution of insecticide resistance. This is caused by mechanisms that reduce insecticide efficacy. Understanding the genetic mechanisms of resistance is essential for DNA based monitoring of resistance in field populations. One such insecticide is indoxacarb, an important selective control option for Helicoverpa armigera in a range of crops including grain, horticulture, and cotton. Recently, a strain of H. armigera (GY7-39) resistant to indoxacarb (198 fold) was isolated from field collected moth. RESULTS To identify the indoxacarb resistance locus, GY7-39 was backcrossed for 6 generations to susceptible strain New GR. In each generation, only resistant males were used to cross back to New GR. Genotype-by-sequencing (GBS) was carried out on 95 H. armigera samples. In total 13203 tags with 8697 unique locations on the H. armigera genome were obtained. The indoxacarb resistance locus in strain GY7-39 was mapped to a 2.5Mbp region on chromosome 16. In this region, two close linked loci (IndoR1 and IndoR2) were found to be associated with indoxacarb resistant GY7-39. CONCLUSIONS We mapped indoxacarb resistance in GY7-39 to two closely linked loci IndoR1 and IndoR2 in a narrowed 2.6Mb region of H. armigera chromosome 16. The results provide essential background data for future genetic investigations including fine mapping of the indoxacarb resistance gene and the eventual development of an effective DNA based diagnostic to support resistance management. This article is protected by copyright. All rights reserved.
THE IMPACT OF NEONATAL UNIT POLICIES ON BREAST MILK FEEDING AT DISCHARGE OF MODERATE PRETERM INFANTS: THE EPIPAGE-2 COHORT STUDY.

Facilitating factors and barriers to breast milk feeding (BMF) for preterm infants have been mainly studied in very preterm populations, but little is known about moderate preterm infants. We aimed to analyze hospital unit characteristics and BMF policies associated with BMF at discharge for infants born at 32 to 34 weeks' gestation (WG). EPIPAGE-2, a French national cohort of preterm births, included 883 infants born at 32 to 34 WG. We investigated kangaroo care (KC) in the first 24 hr, early involvement of parents in feeding support, volume of the unit, BMF information given to mothers hospitalized for threatened preterm delivery, protocols for BMF, presence of a professional trained in human lactation, unit training in neurodevelopmental care, and regional BMF initiation rates in the general population. Multilevel logistic regression analysis was used to investigate associations between unit policies and BMF at discharge, adjusted for individual characteristics and estimating odds ratios (ORs) and 95% confidence intervals (CIs). Overall, 59% (490/828) of infants received BMF at discharge (27% to 87% between units). Rates of BMF at discharge were higher with KC (adjusted OR [aOR] 2.03 [95% CI 1.01, 4.10], early involvement of parents in feeding support (1.94 [1.23, 3.04]), unit training in a neurodevelopmental care program (2.57 [1.18, 5.60]), and in regions with a high level of BMF initiation in the general population (1.85 [1.05, 3.28]). Creating synergies by interventions at the unit and population level may reduce the variability in BMF rates at discharge for moderate preterm infants.
The Niemann–Pick C1-like 1 rs2073547 polymorphism is associated with type 2 diabetes mellitus in a Chinese population

Objective To explore the association between Niemann–Pick C1-like 1 gene (NPC1L1) single nucleotide polymorphisms and type 2 diabetes mellitus (T2DM) in a Chinese population. Methods Using propensity score matching, 490 T2DM patients and 490 matched controls were recruited from 13 communities in Guangxi, China. NPC1L1 rs217386 and rs2073547 genotyping was performed using a MassARRAY system. Results The rs2073547 genotype distribution differed significantly among patient groups. Low-density lipoprotein cholesterol levels were similar among different rs2073547 genotypes and alleles. The rs2073547 AG genotype was significantly more prevalent in patients with T2DM. After adjusting for risk or protective factors for diabetes, AG and GG+AG genotypes of rs2073547 were associated with significantly increased risks of T2DM. Compared with the AA genotype, the AG genotype was associated with a significantly higher risk of T2DM in participants with gamma-glutamyl transpeptidase (GGT) <45 U/L, systolic blood pressure (SBP) ≥140 mmHg, or triglyceride <1.70 mmol/L. In participants with GGT <45 U/L or SBP ≥140 mmHg, the GG+AG genotype was associated with a significantly higher T2DM risk versus the AA genotype. Conclusions The rs2073547 polymorphism of NPC1L1 may be related to T2DM susceptibility in the Chinese population.
Persistent organic pollutants (POPs) increase rage signaling to promote downstream cardiovascular remodeling

Exposure to environmental contaminants and consumption of a high, saturated fatty diet has been demonstrated to promote precursors for metabolic syndrome (hyperglycemia, hyperinsulinemia, and hypertriglyceridemia). The purpose of this study was to determine if exposure to the most prevalent environmental persistent organic pollutants (POPs) would act as causative agents to promote metabolic syndrome independent of dietary intake. We hypothesized that POPs will activate the advanced glycated end‐product (AGE)‐and receptor for AGE (RAGE) signaling cascade to promote downstream signaling modulators of cardiovascular remodeling and oxidative stress in the heart. At 5‐weeks of age nondiabetic (WT) and diabetic (ob/ob) mice were exposed POPs mixtures by oral gavage twice a week for 6‐weeks. At the end of 6‐weeks, animals were sacrificed and the hearts were taken for biochemical analysis. Increased activation of the AGE‐RAGE signaling cascade via POPs exposure resulted in elevated levels of fibroblast differentiation (α‐smooth muscle actin) and RAGE expression indicated maladaptive cardiac remodeling. Conversely, the observed decreased superoxide dismutase‐1 and ‐2 (SOD‐1 and SOD‐2) expression may exacerbate the adverse changes occurring as a result of POPs treatment to reduce innate cardioprotective mechanisms. In comparison, ventricular collagen levels were decreased in mice exposed to POPs. In conclusion, exposure to organic environmental pollutants may intensify oxidative and inflammatory stressors to overwhelm protective mechanisms allowing for adverse cardiac remodeling.