Miracle-dz/UniFAR-FTUs huggingface dataset:
MSH1 is required for maintenance of the low mutation rates in plant mitochondrial and plastid genomes

Significance Plant mitochondrial and plastid genomes maintain unusually low mutation rates, but the mechanisms responsible for their accurate transmission of DNA sequences have remained mysterious. Application of high-fidelity DNA sequencing techniques enabled detection of new mutations still present at low frequencies within tissue samples from the flowering plant Arabidopsis and showed that disrupting a gene in the mutS mismatch repair family (MSH1) increases the frequency of mitochondrial and plastid sequence variants approximately 10-fold to 1,000-fold. This gene has an unusually disjunct distribution across the tree of life, implying a history of horizontal gene transfer among eukaryotes, prokaryotes, and viruses. Its presence in plants and absence in lineages such as animals may contribute to radical differences in organelle mutation rates across eukaryotes. Mitochondrial and plastid genomes in land plants exhibit some of the slowest rates of sequence evolution observed in any eukaryotic genome, suggesting an exceptional ability to prevent or correct mutations. However, the mechanisms responsible for this extreme fidelity remain unclear. We tested seven candidate genes involved in cytoplasmic DNA replication, recombination, and repair (POLIA, POLIB, MSH1, RECA3, UNG, FPG, and OGG1) for effects on mutation rates in the model angiosperm Arabidopsis thaliana by applying a highly accurate DNA sequencing technique (duplex sequencing) that can detect newly arisen mitochondrial and plastid mutations even at low heteroplasmic frequencies. We find that disrupting MSH1 (but not the other candidate genes) leads to massive increases in the frequency of point mutations and small indels and changes to the mutation spectrum in mitochondrial and plastid DNA. We also used droplet digital PCR to show transmission of de novo heteroplasmies across generations in msh1 mutants, confirming a contribution to heritable mutation rates. This dual-targeted gene is part of an enigmatic lineage within the mutS mismatch repair family that we find is also present outside of green plants in multiple eukaryotic groups (stramenopiles, alveolates, haptophytes, and cryptomonads), as well as certain bacteria and viruses. MSH1 has previously been shown to limit ectopic recombination in plant cytoplasmic genomes. Our results point to a broader role in recognition and correction of errors in plant mitochondrial and plastid DNA sequence, leading to greatly suppressed mutation rates perhaps via initiation of double-stranded breaks and repair pathways based on faithful homologous recombination.
Combined PRP and microfat graft for facial disability in systemic sclerosis

Introduction Systemic sclerosis (SSc) is a rare autoimmune disease characterized by fibrosis and microvascular damage. Facial signs are frequent and include perioral skin thickening, facial atrophy and microstomia. Facial handicap is overlooked by physicians but when patients are questioned, they frequently declare discomfort and distress due to their facial disability and appearance. As ideal autologous filler, fat graft has previously been considered in the treatment of facial handicap in SSc. To enhance fat graft survival, we combined fat graft and autologous platelet-rich plasma. Cases Description Two patients suffering from SSc with facial disability, facial skin thickening and aesthetic discomfort were treated with combined subcutaneous microinjection of autologous fat and platelet-rich plasma. Conclusions Regular follow-up until 12 months showed that facial disability decreased, skin texture appeared softer, and mouth opening increased. Patients declared to be very satisfied from a functional and aesthetic point of view until their last follow-up at 12 months. Fat grafting is beneficial in the improvement of facial symptoms of patients with SSc, and the addition of platelet-rich plasma is a feasible, simple and safe method. Further studies are required to better assess the advantage on fat graft retention, trophicity and the lasting effect offered by this combined therapy.
KLF4 Represses DYRK2 Inhibition of Self-renewal and Survival Through c-Myc and p53 in Leukemia Stem/Progenitor Cells.

Leukemia stem cells are a rare population with a primitive progenitor phenotype that can initiate, sustain, and recapitulate leukemia through a poorly understood mechanism of self-renewal. Here, we report that KLF4 promotes disease progression in a murine model of chronic myeloid leukemia (CML)-like myeloproliferative neoplasia by repressing an inhibitory mechanism of preservation in leukemia stem/progenitor cells with leukemia-initiating capacity. Deletion of the Klf4 gene severely abrogated the maintenance of BCR-ABL1(p210)-induced CML by impairing survival and self-renewal in BCR-ABL1+ CD150+ LSK leukemic cells. Mechanistically, KLF4 repressed the Dyrk2 gene in leukemic stem/progenitor cells; thus, loss of KLF4 resulted in elevated levels of DYRK2 kinase, which were associated with inhibition of survival and self-renewal via depletion of c-Myc protein and p53 activation. In addition to transcriptional regulation, stabilization of DYRK2 protein by inhibiting ubiquitin E3 ligase SIAH2 with vitamin K3 promoted apoptosis and abrogated self-renewal in murine and human CML stem/progenitor cells. Altogether, our results suggest that DYRK2 is a molecular checkpoint controlling both p53 and c-Myc-mediated regulation of survival and self-renewal in CML cells with leukemic-initiating capacity that can be targeted with small molecules.
Sous les gölet, les forages. Infrastructures d’irrigation et trajectoires des territoires de l’eau dans la région d’Izmir (Turquie)

En 2012, l’Etat turc a lance un vaste programme de construction de « 1 000 golet en 1 000 jours » pour augmenter les surfaces irriguees. Toutefois, on constate que ces petits reservoirs collinaires, transferes a des groupements d’agriculteurs, sont souvent implantes la ou les agriculteurs irriguent deja a partir de l’eau souterraine et que, d’un village a l’autre, leur appropriation est tres differente. L’article etudie le role d’infrastructures d’irrigation dans la reconfiguration des territoires ruraux dans deux villages de la region d’Izmir. Dans le premier, on observe, dans l’utilisation de forages collectifs puis du golet, une continuite d’irrigation communautaire pour une arboriculture commerciale. Dans le second, des forages prives ont permis de developper un maraichage intensif et cette irrigation individuelle se poursuit dans l’utilisation informelle de l’eau du golet. L’article montre que les objets techniques, dans leur materialite, faconnent et revelent des trajectoires territoriales jamais figees, toujours en mouvement.
¿Influye el valor percibido de las aplicaciones de comercio móvil del sector moda en la aceptación de las alertas publicitarias?

espanolEste trabajo analiza la influencia del valor percibido, desde una perspectiva hedonica-utilitarista, de las aplicaciones de comercio movil de productos de moda en la aceptacion de las comunicaciones en forma de alertas publicitarias moviles. La informacion ha sido recogida a traves de un cuestionario estructurado online dirigido a 340 consumidores que compran productos de moda exclusivamente a traves de una aplicacion de comercio movil en territorio espanol. Los resultados indican que tanto el valor utilitarista como el valor hedonico influyen positivamente sobre la aceptacion de las alertas publicitarias moviles. El estudio realizado aporta una serie de implicaciones gerenciales para la elaboracion de estrategias de marketing y comunicacion EnglishThis study analyzes the influence of the perceived value, from a hedonic-utilitarian perspective, of mobile commerce applications of fashion products in the acceptance of mobile advertising alerts. The data was collected in Spain through a structured online questionnaire answered by 340 consumers who buy fashion products exclusively through a mobile commerce application. The results showed that utilitarian and hedonic value positively influence the acceptance of mobile advertising alerts. The study provides management implications for the development of marketing and communication strategies
Targeted-Ion Mass Spectrometry for the Identification of Forensically Relevant Biological Fluids and Samples from Sexual Assault Evidence

Forensic practitioners have long sought efficient and reliable means for identifying those samples that are best suited for successful genetic profiling. Traditional serological screening methodologies rely upon enzyme activity and antibody-based serological tests. These tests can be consumptive, laborious and costly while reliance on antibody-based serological testing can be prone to error. Positive results resulting from non-target biological fluids, the potential for cross-reactivity and non-specific binding events yield merely presumptive results. This has led forensic biologists to omit serological testing, at least in the case of sexual assault kit samples, in favor of Y-Screen assays. While these YScreen approaches achieve rapid screening of samples for the presence of a detectible male DNA, they do not provide any serological information and therefore lack critical investigative/biological context. A more sensitive and accurate technology for the confirmatory identification of biological fluids would greatly bolster the weight of serological evidence presented in court and assist with more informed sample prioritization. A particularly promising approach combines high-specificity protein biomarkers with a target-ion mass spectrometry. Applying absolute quantitation of protein targets in the biomarker panel
Analysis of Detection of Drow and Entire Co-Occurrence Matrix GLCM Method on The Classification of Image

Grey level co-occurrence matrix or GLCM is a method for obtaining features of a textural image. On the previous study of GLCM, using only 4-degree degrees 0, 45, 90 and 135 in calculating the result of features. Periodicity, directionalityand randomness are the three most important factors in characterizing textures. Therefore, textural directionality is a basic feature of the image and plays an important role in image descriptions, which can be used to describe image textures. So this research will analyse the effect of modification of directionality or direction of adegree of texture distribution on GLCM by using 8 degree direction, which is degree 0, 45, 90, 135, 180, 225, 270, and 315 to know theeffect that impact on theimage by using support vector machine as aclassifier. The results showed that the SVM classifier was not able to work well on GLCM feature extraction, but the performance of the modification resulted in a consistent increase in accuracy by performing 10 tests.
Immunological factors of cardiovascular risk (TNF-α) depending on various hemodynamic forms of arterial hypertension in adolescents.

119 children aged 12-17 years with the stable and labile forms of arterial hypertension (AH) and prehypertension hospitalized to cardiopulmonary department due to ambulatory single-measured blood pressure (BP) elevation were observed. The level of TNF-α in adolescents with different forms of AH and prehypertension as well as the correlation of this marker with other cardiovascular risk factors was determined. There was a significant increase in the mean value (9.50±0.54 pg/ml) and frequency (45.6%) of increase of TNF-α level in the group of children with AH compared with the group of children with normotension (6.43±0,64 pg/ml and 12.5% respectively). There is shown a tendency to increase of TNF-α levels, depending on the degree of stabilization of AH with the highest level of proinflammatory cytokines of TNF-α in the group of children with stable systolic BP. The positive correlation of TNF-α with the daily BP monitoring indicators, especially with the level of diastolic BP and its variability at night was revealed.
Fetal Heart Beat detection based on Empirical Mode Decomposition, Signal Quality Indices and Correlation Analysis

The purpose of fetal monitoring during childbirth is the early recognition of any pathological conditions to guide a clinician in early intervention to avoid any complication in the health of the fetus. Non-Invasive Fetal Electrocardiography (NIFECG) represents an alternative fetal monitoring technique. The fetal ECG (fECG) derived from maternal thoracic and abdominal ECG recordings, provides an alternative to typical embryo monitoring means. In addition, it allows for long-term and ambulatory registrations that broaden the diagnostic capabilities for assessing the fetal health. However, in real situations, clear fECG is difficult to extract because it is usually overwhelmed by the dominant maternal ECG and other contaminated noise such as baseline wander and high-frequency interference. In this paper, a novel integrated adaptive methodology based on the combination of blind source separation, empirical mode decomposition, wavelet shrinkage denoising and correlation analysis, for the non-invasive extraction and processing of the FECG, is proposed. The methodology has been evaluated using both real and simulated recordings, and the obtained results indicate it efficiently.
Improving Driver Engagement During L2 Automation: A Pilot Study

Summary: Advanced technologies such as adaptive cruise control and lane keeping are key components of SAE Level 2 vehicle automation. As such automation becomes widespread, drivers may be less engaged in driving because they assume that vehicles can safely mitigate risks. However, L2 automation cannot handle the full spectrum of driving situations and will require manual control in many situations. Drivers unprepared to take control may make suboptimal, delayed, or dangerous decisions during and after reengaging with the driving task. This highlights the need for efficient ways to help drivers re-engage with driving. This paper describes an evaluation of a conceptual driver engagement system that combined driver data with contextual data to communicate appropriate information during L2 operations. The system was compared to a traditional, staged-alert system that only monitored driver gaze with no contextual information. Results indicate higher situation awareness, higher levels of trust and satisfaction, no increase in workload, with evidence of improve off-road glance behaviors when driving with the conceptual system. These findings can help inform further development and testing of driver engagement approaches using driver monitoring.
Communicating Imperatives Requires Psychological Closeness But Creates Psychological Distance

This article evaluates the psychological correlates of imperative speech through pronouns. We demonstrate that people communicate with more collective immediacy (“we” words) when using imperatives than nonimperatives in an experiment (Study 1, N = 828) and field studies of American politicians (Study 2a: N = 123,678 speeches), and Joseph Stalin (Study 2b: N = 593 speeches). However, respondents experience a psychological distancing effect after an imperative (fewer “I” words). This experimental pattern (Study 3: N = 852) also holds in the field using U.S. Supreme Court dissents from the Roberts Court (Study 4: N = 644). Exploratory findings suggest that third-person plural pronouns (“they” words) are used more when communicating imperative speech relative to nonimperative speech. Our evidence supports an interpersonal imperatives asymmetry: imperatives demand psychological support when communicating how the world must be, but they undermine the autonomy of respondents. Social and psychological implications of these data are discussed.
Phase Ib study of dulanermin combined with FOLFIRI (with or without bevacizumab [BV]) in previously treated patients (Pts) with metastatic colorectal cancer (mCRC).

3543 Background: Dulanermin is a recombinant soluble human Apo2 ligand/TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) that activates apoptotic pathways by binding to the pro-apoptotic death receptors DR4 and 5. This is the final update of the study assessing the safety of dulanermin combined with FOLFIRI (± BV) in previously treated mCRC pts. Methods: This was a multicenter, open-label, dose-escalation and cohort expansion study. Dulanermin was administered intravenously in 14-day cycles on Days 1, 2 and 3 at 9 mg/kg or 18 mg/kg, with FOLFIRI (+ BV in pts not previously treated with BV) on Day 1. Dose-limiting toxicity (DLT) was assessed through 2 cycles (28 days). Adverse events (AE) were recorded through all cycles. Response was assessed with RECIST (v1.0). Results: A total of 27 pts received 1-48 cycles (median 10) of dulanermin with FOLFIRI (1 pt received BV). No DLTs were reported and no relationship between dulanermin dose level and AE incidence or severity was detected. The most frequent AEs r.
BİST Şehir Endekslerinde Ay İçi ve Ay Dönümü Anomalilerinin İncelenmesi

Bu calismanin amaci , Borsa Istanbul (BIST) Şehir Endeksinde yer alan nufusu en yogun bes sehirde (Istanbul, Ankara, Izmir, Bursa, Antalya) 01.08. 2010 – 01.08. 2019 doneminde ay ici ve ay donumu anomalilerin varliginin incelenmesidir. Calisma kapsaminda, getirilerin hesaplanmasi icin soz konusu sehirlerin borsa endekslerinin (XSIST, XSANK, XSIZM, XSBUR, XSANT) gunluk kapanis fiyatlarindan yararlanilmistir. Analiz doneminde en yuksek ortalama getirinin Izmir Şehir Endeksinde, en dusuk ortalama getirinin ise Antalya Şehir Endeksinde oldugu gorulmustur. Anomalilerin incelenmesinde, degisen varyans (heteroskedastisite) sorununun bulunmasi nedeniyle kukla degiskenlerin yer aldigi GARCH (1,1) modeli kullanilmistir. Analizlerin sonucunda, Istanbul disindaki dort sehir endeksinde ay ici anomalisi, nufus acisindan en buyuk uc sehir olan Istanbul, Ankara ve Izmir Endekslerinde ise ay donumu anomalisi tespit edilmistir.
Alterações da personalidade na demência: Uma revisão

The present review aimed to analyze empirical studies that have investigated the personality changes in dementia, based on the Five Factor Model of Personality. We systematically reviewed empirical articles indexed in the following databases EBSCO/Web of Knowledge/Medline/Pubmed/SciELO/Scopus. Fifty-seven articles were included. The personality changes are evident in the early stages of dementia and could be an early clinical marker. A data appears to be generally transverse and unanimous, there is evidence of an increase in personality trait Neuroticism and a decrease in personality trait Consciousness. It is suggested the need for systematic investigations, in order to increase the sensitivity of early diagnosis and practical utility in terms of current clinical diagnosis in Alzheimer’s dementia, with the introduction of personality evaluation.
Relación entre el strain rate y la estructura miocárdica en la estenosis aórtica grave Relationship between Strain Rate and Myocardial Structure in Severe Aortic Stenosis

Background: In severe symptomatic aortic stenosis (SSAS) altered global longitudinal systolic strain (GLSS) would correlate with changes in myocardial histological architecture and could identify early contractile involvement in patients with preserved ejection fraction (PEF). Objective: The aim of this study was to analyze GLSS, collagen volume (CV), myocyte area (MyAr) and contractile involvement in patients with SSAS and PEF. Methods: Twenty six patients with SSAS and PEF (67±11 years old, 53% male) were included in the study. A preoperative hemodynamic study and an intraoperative endomyocardial biopsy were performed to determine CV and MyAr. Three groups of patients were identified: G1: compensated left ventricular hypertrophy (LVH) without coronary disease (n=8); G2: decompensated LVH without coronary disease (n=7) and G3: decompensated LVH with coronary disease (n=11). GLSS was normalized by stroke volume, meridional end-systolic wall stress (δ) and end-diastolic diameter (EDD). Results: No significant differences in stroke volume, δ and EDD were observed between groups G1, G2 and G3. Differences between groups were observed in: CV (%) (G1: 4.7 ± 1.2, G2: 8.4 ± 1.2, G3: 11.0 ± 3.0; p < 0.01), MyAr (mm 2 ) (G1: 328.7 ± 66.2, G2: 376.7 ± 21.9, G3: 385.0 ± 13.0; p = 0.01), LVEDP (mm Hg) (G1: 13.1 ± 1.5, G2: 19.0 ± 3.8, G3: 23.6 ± 5.8; p < 0.01), +dP/dt max (mm Hg/sec / LVEDP, mm Hg) (G1: 176.4 ± 45.5, G2: 89.6 ± 20.1, G3: 113.1 ± 43.7; p < 0.01), and GLSS (%) (G1: -17.9 ± 4.2, G2: -13.5 ± 2.5, G3: -13.6 ± 3; p = 0.021). GLSS correlated with CV and LVEDP and it evidenced a trend to correlate with a contractility index (+dP/dt max mm Hg/s / LVEDP, mm Hg). Conclusions: Altered GLSS in patients with SSAS and PEF expresses myocardial structural changes related to increase in CV, which is associated with enhanced LVEDP and probable myocardial contractile failure.
Análisis de redes en twitter para la inserción en comunidades : El caso de un producto agroindustrial

The hashtags and relevant content in Twitter, related to the agroindustrial product mezcal were analysed, and the so-called ‘influencers’ were also identified. For doing this, 57.362 tweets were extracted and stored; three networks were built: users-hashtags, retweets, and mentions, which were studied by using social network analysis (SNA). The application of the SNA allowed revealing certain kind of hidden patterns within the social media complex relationships, which can be useful for designing strategies aimed at positioning actors and spread information. The results allow stating that in order to get inserted in the social network, the following should be considered: the use of combined hashtags, the message content kind, including pictures attached, and mentioning the most influential accounts who are embedded in already formed communities.
Dynamic chromatin accessibility landscape changes following interleukin-1 stimulation

Genome-wide methods for examining chromatin modification provide detailed information on regulatory regions of the genome. Dynamic modifications of chromatin allow rapid access of the gene regulatory machinery to condensed genomic regions facilitating subsequent gene expression. Inflammatory cytokine stimulation of cells can cause rapid gene expression changes through direct signalling pathway-mediated transcription factor activation and regulatory element binding. Here we used the Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) to assess regions of the genome that are differentially accessible following treatment of cells with interleukin-1 (IL-1). We identified 126,483 open chromatin regions, with 241 regions significantly differentially accessible following stimulation, with 64 and 177 more or less accessible, respectively. These differentially accessible regions predominantly correspond to regions of the genome marked as enhancers. Motif searching identified an overrepresentation of a number of transcription factors, most notably RelA in the regions becoming more accessible, with analysis of ChIP-seq data confirmed RelA binding to these regions. A significant correlation in differential chromatin accessibility and gene expression was also observed. Functionality in regulating gene expression was confirmed using CRISPR/Cas9 genome-editing to delete regions for that became more accessible following stimulation in the genes MMP13, IKBKE and C1QTNF1. These same regions were also accessible for activation using a dCas9-transcriptional activator and showed enhancer activity in a cellular model. Together, these data describe and functionally validate a number of dynamically accessible chromatin regions involved in inflammatory signalling.