Miracle-dz/UniFAR-FTUs huggingface dataset:
Controllable Urokinase Gene Expression in Trabecular Meshwork Cells

Purpose: Glaucoma is a type of progressive optic neuropathy that finally leads to blindness related to elevated intraocular pressure (IOP). Accumulation of extracellular matrix in trabecular meshwork (TM) and juxta-canalicular connective tissues, which form an aqueous outflow pathway, may be a major cause of increased IOP, thus the fibrinolytic system may be associated with regulation of IOP. We examined the possibility of controllable urokinase plasminogen activator (uPA) gene transfer into TM cells.Methods: TM cells were freshly isolated from porcine eyes and human TM cells obtained during trabeculectomy procedures and cultured. Total RNA was extracted from human TM cells and reverse transcribed into cDNA. A reverse-transcribed polymerase chain reaction (RT-PCR) method was then performed to detect the gene expression of uPA. The cDNA of human uPA was sub-cloned into an expression vector (pEYFP-N1 vector) and controllable expression vector (TRE-Tight vector), then each vector was independently transfected into cultured porcine TM cells. Doxycycline was added to the culture medium to activate the pTet-ON and TRE-Tight vectors. Finally, the expression of uPA was examined using an enzyme linked immunosorbent assay (ELISA). Results: ELISA findings revealed the expression of uPA (3.5 ng/ml) in medium from cultured porcine TM cells that had been transfected with the human uPA gene using the pEYFP-N1 vector. Doxycycline induced human uPA in the pTet-On and TRE-Tight vectors with human uPA gene co-transfected TM cells in a dose-dependent manner.Conclusions: Controllable gene transfer of uPA, which may degrade the extracellular matrix in juxta-canalicular connective tissue, into TM cells was achieved using a Tet-On system. The present method may be useful as a novel therapy for glaucoma.
Hierarchical Association Coefficient Algorithm

Suppose that members in a universal set categorized based on observations, and that categories can be stratified based on the average of observations within each category. Two sorting extremes can be obtained from the perspective of arbitrariness of an order of observations. The first sorting extreme is an increasing order of observations on ascendingly stratified categories. The second sorting extreme is a decreasing order of observations on ascendingly stratified categories. Hierarchical association coefficient (HA-coefficient) algorithm is based on a principle that any order of observations in stratified categorization can be placed between the two sorting extremes. The algorithm produces a proportion of how much an order of observations in stratified categorization is close to the first sorting extreme, or how much an order of categorized observations is distant from the second sorting extreme. This paper introduces a theory about the HA-coefficient algorithm, and shows its applications with example data. In addition, proving a reliability of the algorithm is shown through a simulation.
Chromosome Numbers and Karyotypes of Six Oxytropis Species (Fabaceae) from the Qinghai-Tibetan Plateau, China

Chromosome numbers and karyotypes of 13 populations of six Oxytropis species (Fabaceae) from the Qinghai-Tibetan Plateau, China, were presented. The chromosome numbers and karyotypes in O.ochrocephala, O.tatarica, O.kansuensis and O.humifusa (2n=16) were reported for the first time. B-chromosomes were found from O.stracheyana (2n=48). The basic chromosome number of x=8 is confirmed for the genus. The available chromosomal data indicate that polyploidy may have played an important role in the evolution of the genus, with the incidence of polyploidy in the genus reaching 58%. However, our results indicated that among the populations here examined only one was a hexaploid with 2n=48. Such a chromosomal pattern indicates that the karyotypic repatterning at the diploid level seems to be the predominant feature of chromosomal evolution in the Oxytropis species from the Qinghai-Tibetan Plateau, and that sympatric speciation via hybridization and polyploidization has played a minor role in the species diversification of the genus from this area.
MiR-940 promotes malignant progression of breast cancer by regulating FOXO3

Abstract Breast cancer (BC) is a common cancer with poor survival. The present study aimed to explore the effect of miR-940 on the process of BC cells and its target gene FOXO3. The expression of miR-940 was assessed in BC tissues and cells using qRT-PCR. Furthermore, the correlation between miR-940 and prognosis of BC patients from the TCGA database was analyzed. CCK8 assays and colony formation assays were used to explore the effect of miR-940 on BC cell proliferation. The invasion abilities were detected by transwell assays. Luciferase reporter assay was performed to scrutinize the relationship between miR-940 and FOXO3. Finally, rescue experiments were performed through FOXO3 down-regulation and miR-940 inhibitors by using CCK8 assays, colony formation assays and transwell assays. miR-940 was significantly up-regulated in BC cells and tissues. In addition, the high level of miR-940 correlated with poor survival of BC patients (P=0.023). CCK8 assays, colony formation assays and transwell assays indicated that miR-940 promoted the proliferation and invasion abilities of BC cells. The luciferase reporter assay suggested that miR-940 directly targeted FOXO3. Moreover, we found that the effect of si-FOXO3 was rescued by miR-940 inhibitors in BC cells. miR-940 may promote the proliferation and invasion abilities of BC cells by targeting FOXO3. Our study suggested that miR-940 could be a novel molecular target for therapies against BC.
Tibial lengthening using a retrograde magnetically driven intramedullary lengthening device in 10 patients with preexisting ankle and hindfoot fusion

Background and purpose — Motorized intramedullary lengthening nails (ILNs) have been developed as an alternative to external fixators for long bone lengthening. The antegrade approach represents the standard method for tibial ILN insertion. In patients with preexisting ankle and hindfoot fusion a retrograde approach provides an alternative technique that has not been evaluated so far. We report the outcome of this method in 10 patients. Patients and methods — This retrospective study included 10 patients (mean age 18 years [13–25]) with preexisting ankle and hindfoot fusion who underwent tibial lengthening with a retrograde ILN (PRECICE). The mean leg length discrepancy (LLD) was 58 mm (36–80). The underlying conditions were congenital (n = 9) and post tumor resection (n = 1). The main outcome measures were: ILN reliability, distraction achieved, distraction index (DIX), time to bone healing, consolidation index (CIX), complications, and functional results. Results — All patients achieved the goal of lengthening (mean 48 mm [26–80]). Average DIX was 0.6 mm/day (0.5–0.7) and mean CIX was 44 days/cm (26–60). Delayed consolidation occurred in 2 patients and healed after ILN dynamization or nail exchange with grafting. Toe contractures in 2 other patients were resolved with physiotherapy or tenotomy. Until last follow-up (mean 18 months [12–30]) no true complications were encountered, knee motion remained unaffected, and full osseous consolidation occurred in all patients. Interpretation — In patients with LLD and preexisting ankle and hindfoot fusion distal tibial lengthening using a retrograde ILN is a reliable alternative to the standard approach with equivalent bone healing potential and low complication rates leaving the knee unaffected.
Characterisation and assessment of genetic diversity in cultivated and wild carob (Ceratonia siliqua L.) genotypes using AFLP markers

Summary Carob (Ceratonia siliqua L.) is a trioecious evergreen legume tree native to the Middle East and widespread throughout the Mediterranean as a crop, or as part of the maquis. Amplified Fragment Length Polymorphism (AFLP) markers were used to estimate intra-specific genetic diversity among 41 carob genotypes from different areas of the eastern and western Mediterranean basin. Italian and Spanish cultivated varieties were included in the study for fingerprinting. A total of 96 unambiguous polymorphic loci were scored from seven Eco RI/Mse I primer combinations. Simple matching similarity coefficients between pairs of genotypes ranged from 0.542 to 1.000, indicating a high level of intra-specific diversity. AFLP markers clearly discriminated between all the accessions, except for two Sicilian varieties. An UPGMA (Unweighted Pair Group Method with Arithmetic Mean) dendrogram and a Principal Co-ordinates Analysis revealed a broad relationship between the clusters and the geographic origin of the genotypes, with few exceptions. Most of the hermaphrodite varieties belonged to the same cluster, indicating that these cultivars were probably selected in a specific area, then distributed elsewhere. Moreover, an analysis of molecular variance (AMOVA) revealed a high level of “within geographic area” differences.
CAMSAP1 breaks the homeostatic microtubule network to instruct neuronal polarity

Significance Proper formation of axon/dendrites is critical for the neuron to fulfill its function, and microtubules are the final performer in this process. However, how polarizing signals transduce to microtubules to instruct axon/dendrite differentiation remains unknown. Here we found that CAMSAP1, a microtubule minus-end binding protein, drives neuronal polarization, migration, and cortical lamination. We also demonstrate that the microtubule-binding ability of CAMSAP1 is critical for the protection of microtubule minus-ends and preservation of the “seeds” for microtubule regeneration, and this ability is regulated by MARK2. Thus, our findings reveal that CAMSAP1 controls neuronal polarization via triggering an unbalanced distribution of microtubules among neuronal processes; CAMSAP family members regulate axon formation by changing the quantity and quality of microtubules. The establishment of axon/dendrite polarity is fundamental for neurons to integrate into functional circuits, and this process is critically dependent on microtubules (MTs). In the early stages of the establishment process, MTs in axons change dramatically with the morphological building of neurons; however, how the MT network changes are triggered is unclear. Here we show that CAMSAP1 plays a decisive role in the neuronal axon identification process by regulating the number of MTs. Neurons lacking CAMSAP1 form a multiple axon phenotype in vitro, while the multipolar-bipolar transition and radial migration are blocked in vivo. We demonstrate that the polarity regulator MARK2 kinase phosphorylates CAMSAP1 and affects its ability to bind to MTs, which in turn changes the protection of MT minus-ends and also triggers asymmetric distribution of MTs. Our results indicate that the polarized MT network in neurons is a decisive factor in establishing axon/dendritic polarity and is initially triggered by polarized signals.
Effect of Vitamin D3 Supplementation on Severe Asthma Exacerbations in Children With Asthma and Low Vitamin D Levels: The VDKA Randomized Clinical Trial.

Importance Severe asthma exacerbations cause significant morbidity and costs. Whether vitamin D3 supplementation reduces severe childhood asthma exacerbations is unclear. Objective To determine whether vitamin D3 supplementation improves the time to a severe exacerbation in children with asthma and low vitamin D levels. Design, Setting, and Participants The Vitamin D to Prevent Severe Asthma Exacerbations (VDKA) Study was a randomized, double-blind, placebo-controlled clinical trial of vitamin D3 supplementation to improve the time to severe exacerbations in high-risk children with asthma aged 6 to 16 years taking low-dose inhaled corticosteroids and with serum 25-hydroxyvitamin D levels less than 30 ng/mL. Participants were recruited from 7 US centers. Enrollment started in February 2016, with a goal of 400 participants; the trial was terminated early (March 2019) due to futility, and follow-up ended in September 2019. Interventions Participants were randomized to vitamin D3, 4000 IU/d (n = 96), or placebo (n = 96) for 48 weeks and maintained with fluticasone propionate, 176 μg/d (6-11 years old), or 220 μg/d (12-16 years old). Main Outcomes and Measures The primary outcome was the time to a severe asthma exacerbation. Secondary outcomes included the time to a viral-induced severe exacerbation, the proportion of participants in whom the dose of inhaled corticosteroid was reduced halfway through the trial, and the cumulative fluticasone dose during the trial. Results Among 192 randomized participants (mean age, 9.8 years; 77 girls [40%]), 180 (93.8%) completed the trial. A total of 36 participants (37.5%) in the vitamin D3 group and 33 (34.4%) in the placebo group had 1 or more severe exacerbations. Compared with placebo, vitamin D3 supplementation did not significantly improve the time to a severe exacerbation: the mean time to exacerbation was 240 days in the vitamin D3 group vs 253 days in the placebo group (mean group difference, -13.1 days [95% CI, -42.6 to 16.4]; adjusted hazard ratio, 1.13 [95% CI, 0.69 to 1.85]; P = .63). Vitamin D3 supplementation, compared with placebo, likewise did not significantly improve the time to a viral-induced severe exacerbation, the proportion of participants whose dose of inhaled corticosteroid was reduced, or the cumulative fluticasone dose during the trial. Serious adverse events were similar in both groups (vitamin D3 group, n = 11; placebo group, n = 9). Conclusions and Relevance Among children with persistent asthma and low vitamin D levels, vitamin D3 supplementation, compared with placebo, did not significantly improve the time to a severe asthma exacerbation. The findings do not support the use of vitamin D3 supplementation to prevent severe asthma exacerbations in this group of patients. Trial Registration ClinicalTrials.gov Identifier: NCT02687815.
The potential role of mechanically sensitive ion channels in the physiology, injury, and repair of articular cartilage

Biomechanical factors play an extremely important role in regulating the function of articular chondrocytes. Understanding the mechanical factors that drive chondrocyte biological responses is at the heart of our interpretation of cascade events leading to changes in articular cartilage osteoarthritis. The mechanism by which mechanical load is transduced into intracellular signals that can regulate chondrocyte gene expression remains largely unknown. The mechanically sensitive ion channel (MSC) may be one of its specific mechanisms. This review focuses on four ion channels involved in the mechanotransduction of chondrocytes, exploring their properties and the main factors that activate the associated pathways. The upstream and downstream potential relationships between the protein pathways were also explored. The specific biophysical mechanism of the chondrocyte mechanical microenvironment is becoming the focus of research. Elucidating the mechanotransduction mechanism of MSC is essential for the research of biophysical pathogenesis and targeted drugs in cartilage injury-related diseases.
Phylogenetic Relationships of the Sceloporus scalaris Species Group (Squamata)

ka's alligator and other taxa. Technical Report #53, pp. 7-35. FL Coop. Fish Wild. Res. Unit. , Univ. Fl. SELYE, H. 1936. A syndrome produced by diverse nocuous agents. Nature 138:32. VONIER, P. M. , D. A. CRAIN, J. A. MCLACHLAN, L. J. GUILLETTE, JR., AND S. E ARNOLD. 1996. Interaction of environmental chemicals with the estrogen and progesterone receptors from the oviduct of the American alligator. Environ. Health Perspec. 104: 1318-1322.
Integration of pluripotency pathways regulates stem cell maintenance in the Arabidopsis shoot meristem

Significance Pluripotent stem cells are critical in both animal and plant development. Unlike higher animals, plants have unique postembryonic development, which continuously produce organs depending on shoot and root meristems. In the shoot meristem, division of the stem cells in the outermost layers provides the cells for all shoot structures. How those meristem cells are tightly controlled attracted intense studies. Genetic and molecular analyses in Arabidopsis have identified the key transcription factors WUSCHEL (WUS) and SHOOTMERISTEMLESS (STM) as the major regulators of pluripotency in the shoot meristem. Here, the results provide solid evidence showing how those two pluripotency factors WUS and STM coordinate to control shoot meristem cells strictly in plants. In the shoot meristem, both WUSCHEL (WUS) and SHOOT MERISTEMLESS (STM), two transcription factors with overlapping spatiotemporal expression patterns, are essential for maintaining stem cells in an undifferentiated state. Despite their importance, it remains unclear how these two pathways are integrated to coordinate stem cell development. Here, we show that the WUS and STM pathways in Arabidopsis thaliana converge through direct interaction between the WUS and STM proteins. STM binds to the promoter of CLAVATA3 (CLV3) and enhances the binding of WUS to the same promoter through the WUS–STM interaction. Both the heterodimerization and simultaneous binding of WUS and STM at two sites on the CLV3 promoter are required to regulate CLV3 expression, which in turn maintains a constant number of stem cells. Furthermore, the expression of STM depends on WUS, and this WUS-activated STM expression enhances the WUS-mediated stem cell activity. Our data provide a framework for understanding how spatial expression patterns within the shoot meristem are translated into regulatory units of stem cell homeostasis.
Country of birth, time period of resettlement and subsequent treated common mental disorders in young refugees in Sweden

Abstract Background Little is known regarding treatment for common mental disorders (CMDs) in young refugees. We aimed to identify (i) if the risk of treatment for CMDs in young refugees varies by their country of birth, compared with the Swedish-born population and (ii) if time period of resettlement influences these possible associations. Methods All Swedish-born individuals and people who were granted refugee status, aged 16–25 years, living in Sweden on 31 December 1999, 2004 or 2009 (around 1 million people with 3–4% refugees in each cohort), were followed for 4 years for treated CMDs by linking register data. To facilitate stratified analyses by refugees’ country of birth, the 2009 cohort was followed for 7 years with regard to specialized healthcare and antidepressant prescription due to CMDs. Hazard ratios with 95% confidence intervals were computed in crude and adjusted models. Results Refugees in the 2009 cohort with 7-year follow-up had a 25% lower risk for treated CMDs, compared with the Swedish-born. Stratified analysis by country of birth showed a similarly lower risk regarding treated CMDs among refugees from all countries but Iran [hazard ratios (95% confidence intervals): 1.15 (1.05–1.26)] than their Swedish-born peers. No substantial effect of time period of resettlement was observed in the risk for treated CMDs in refugees. Conclusions Treatment for CMDs is lower in young refugees than in the majority population in Sweden, is stable across time, but varies with country of birth. Strategies to improve access to mental healthcare for young refugees are warranted.
The Microbial Community Associated with Rhizostoma pulmo: Ecological Significance and Potential Consequences for Marine Organisms and Human Health

Jellyfish blooms are frequent and widespread in coastal areas worldwide, often associated with significant ecological and socio-economic consequences. Recent studies have also suggested cnidarian jellyfish may act as vectors of bacterial pathogens. The scyphomedusa Rhizostoma pulmo is an outbreak-forming jellyfish widely occurring across the Mediterranean basin. Using combination of culture-based approaches and a high-throughput amplicon sequencing (HTS), and based on available knowledge on a warm-affinity jellyfish-associated microbiome, we compared the microbial community associated with R. pulmo adult jellyfish in the Gulf of Taranto (Ionian Sea) between summer (July 2016) and winter (February 2017) sampling periods. The jellyfish-associated microbiota was investigated in three distinct compartments, namely umbrella, oral arms, and the mucus secretion. Actinobacteria, Bacteroidetes, Chlamydiae, Cyanobacteria, Deinococcus-Thermus, Firmicutes, Fusobacteria, Planctomycetes, Proteobacteria, Rhodothermaeota, Spirochaetes, Tenericutes, and Thaumarchaeota were the phyla isolated from all the three R. pulmo compartments in the sampling times. In particular, the main genera Mycoplasma and Spiroplasma, belonging to the class Mollicutes (phylum Tenericutes), have been identified in all the three jellyfish compartments. The taxonomic microbial data were coupled with metabolic profiles resulting from the utilization of 31 different carbon sources by the BIOLOG Eco-Plate system. Microorganisms associated with mucus are characterized by great diversity. The counts of culturable heterotrophic bacteria and potential metabolic activities are also remarkable. Results are discussed in terms of R. pulmo ecology, the potential health hazard for marine and human life as well as the potential biotechnological applications related to the associated microbiome.
Regulation of the thrombin/protease-activated receptor 1 axis by chemokine (CXC motif) receptor 4

The chemokine receptor CXCR4, a G protein–coupled receptor (GPCR) capable of heteromerizing with other GPCRs, is involved in many processes, including immune responses, hematopoiesis, and organogenesis. Evidence suggests that CXCR4 activation reduces thrombin/protease-activated receptor 1 (PAR1)-induced impairment of endothelial barrier function. However, the mechanisms underlying cross-talk between CXCR4 and PAR1 are not well-understood. Using intermolecular bioluminescence resonance energy transfer and proximity ligation assays, we found that CXCR4 heteromerizes with PAR1 in the HEK293T expression system and in human primary pulmonary endothelial cells (hPPECs). A peptide analog of transmembrane domain 2 (TM2) of CXCR4 interfered with PAR1:CXCR4 heteromerization. In HTLA cells, the presence of CXCR4 reduced the efficacy of thrombin to induce β-arrestin-2 recruitment to recombinant PAR1 and enhanced thrombin-induced Ca2+ mobilization. Whereas thrombin-induced extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation occurred more transiently in the presence of CXCR4, peak ERK1/2 phosphorylation was increased when compared with HTLA cells expressing PAR1 alone. CXCR4-associated effects on thrombin-induced β-arrestin-2 recruitment to and signaling of PAR1 could be reversed by TM2. In hPPECs, TM2 inhibited thrombin-induced ERK1/2 phosphorylation and activation of Ras homolog gene family member A. CXCR4 siRNA knockdown inhibited thrombin-induced ERK1/2 phosphorylation. Whereas thrombin stimulation reduced surface expression of PAR1, CXCR4, and PAR1:CXCR4 heteromers, chemokine (CXC motif) ligand 12 stimulation reduced surface expression of CXCR4 and PAR1:CXCR4 heteromers, but not of PAR1. Finally, TM2 dose-dependently inhibited thrombin-induced impairment of hPPEC monolayer permeability. Our findings suggest that CXCR4:PAR1 heteromerization enhances thrombin-induced G protein signaling of PAR1 and PAR1-mediated endothelial barrier disruption.