Miracle-dz/UniFAR-FTUs huggingface dataset:
Macrophage Mitochondrial Biogenesis and Metabolic Reprogramming Induced by Leishmania donovani Require Lipophosphoglycan and Type I Interferon Signaling

To colonize host phagocytes, Leishmania metacyclic promastigotes subvert host defense mechanisms and create a specialized intracellular niche adapted to their replication. This is accomplished through the action of virulence factors, including the surface coat glycoconjugate lipophosphoglycan. ABSTRACT Pathogen-specific rewiring of host cell metabolism creates the metabolically adapted microenvironment required for pathogen replication. Here, we investigated the mechanisms governing the modulation of macrophage mitochondrial properties by the vacuolar pathogen Leishmania. We report that induction of oxidative phosphorylation and mitochondrial biogenesis by Leishmania donovani requires the virulence glycolipid lipophosphoglycan, which stimulates the expression of key transcriptional regulators and structural genes associated with the electron transport chain. Leishmania-induced mitochondriogenesis also requires a lipophosphoglycan-independent pathway involving type I interferon (IFN) receptor signaling. The observation that pharmacological induction of mitochondrial biogenesis enables an avirulent lipophosphoglycan-defective L. donovani mutant to survive in macrophages supports the notion that mitochondrial biogenesis contributes to the creation of a metabolically adapted environment propitious to the colonization of host cells by the parasite. This study provides novel insight into the complex mechanism by which Leishmania metacyclic promastigotes alter host cell mitochondrial biogenesis and metabolism during the colonization process. IMPORTANCE To colonize host phagocytes, Leishmania metacyclic promastigotes subvert host defense mechanisms and create a specialized intracellular niche adapted to their replication. This is accomplished through the action of virulence factors, including the surface coat glycoconjugate lipophosphoglycan. In addition, Leishmania induces proliferation of host cell mitochondria as well as metabolic reprogramming of macrophages. These metabolic alterations are crucial to the colonization process of macrophages, as they may provide metabolites required for parasite growth. In this study, we describe a new key role for lipophosphoglycan in the stimulation of oxidative phosphorylation and mitochondrial biogenesis. We also demonstrate that host cell pattern recognition receptors Toll-like receptor 4 (TLR4) and endosomal TLRs mediate these Leishmania-induced alterations of host cell mitochondrial biology, which also require type I IFN signaling. These findings provide new insight into how Leishmania creates a metabolically adapted environment favorable to their replication.
Lyssavirus P Protein Isoforms Diverge Significantly in Subcellular Interactions Underlying Mechanisms of Interferon Antagonism

Lyssaviruses, including rabies virus, cause rabies, a progressive encephalomyelitis that is almost invariably fatal. There are no effective antivirals for symptomatic infection, and effective application of current vaccines is limited in areas of endemicity, such that rabies causes ~59,000 deaths per year. ABSTRACT Viral hijacking of microtubule (MT)-dependent transport is well understood, but several viruses also express discrete MT-associated proteins (vMAPs), potentially to modulate MT-dependent processes in the host cell. Specific roles for vMAP-MT interactions include subversion of antiviral responses by P3, an isoform of the P protein of rabies virus (RABV; genus Lyssavirus), which mediates MT-dependent antagonism of interferon (IFN)-dependent signal transducers and activators of transcription 1 (STAT1) signaling. P3 also undergoes nucleocytoplasmic trafficking and inhibits STAT1-DNA binding, indicative of intranuclear roles in a multipronged antagonistic strategy. MT association/STAT1 antagonist functions of P3 correlate with pathogenesis, indicating potential as therapeutic targets. However, key questions remain, including whether other P protein isoforms interact with MTs, the relationship of these interactions with pathogenesis, and the extent of conservation of P3-MT interactions between diverse pathogenic lyssaviruses. Using super-resolution microscopy, live-cell imaging, and immune signaling analyses, we find that multiple P protein isoforms associate with MTs and that association correlates with pathogenesis. Furthermore, P3 proteins from different lyssaviruses exhibit variation in intracellular localization phenotypes that are associated with STAT1 antagonist function, whereby P3-MT association is conserved among lyssaviruses of phylogroup I but not phylogroup II, while nucleocytoplasmic localization varies between P3 proteins of the same phylogroup within both phylogroup I and II. Nevertheless, the divergent P3 proteins retain significant IFN antagonist function, indicative of adaptation to favor different inhibitory mechanisms, with MT interaction important to phylogroup I viruses. IMPORTANCE Lyssaviruses, including rabies virus, cause rabies, a progressive encephalomyelitis that is almost invariably fatal. There are no effective antivirals for symptomatic infection, and effective application of current vaccines is limited in areas of endemicity, such that rabies causes ~59,000 deaths per year. Viral subversion of host cell functions, including antiviral immunity, is critical to disease, and isoforms of the lyssavirus P protein are central to the virus-host interface underpinning immune evasion. Here, we show that specific cellular interactions of P protein isoforms involved in immune evasion vary significantly between different lyssaviruses, indicative of distinct strategies to evade immune responses. These findings highlight the diversity of the virus-host interface, an important consideration in the development of pan-lyssavirus therapeutic approaches.
Mitochondrial fitness and cancer risk

Changes in metabolism are a hallmark of cancer, but molecular signatures of altered bioenergetics to aid in clinical decision-making do not currently exist. We recently identified a group of human tumors with constitutively reduced expression of the mitochondrial structural protein, Mic60, also called mitofilin or inner membrane mitochondrial protein (IMMT). These Mic60-low tumors exhibit severe loss of mitochondrial fitness, paradoxically accompanied by increased metastatic propensity and upregulation of a unique transcriptome of Interferon (IFN) signaling and Senescence-Associated Secretory Phenotype (SASP). Here, we show that an optimized, 11-gene signature of Mic60-low tumors is differentially expressed in multiple malignancies, compared to normal tissues, and correlates with poor patient outcome. When analyzed in three independent patient cohorts of pancreatic ductal adenocarcinoma (PDAC), the Mic60-low gene signature was associated with aggressive disease variants, local inflammation, FOLFIRINOX failure and shortened survival, independently of age, gender, or stage. Therefore, the 11-gene Mic60-low signature may provide an easily accessible molecular tool to stratify patient risk in PDAC and potentially other malignancies.
Quantifying nonclassicality with local unitary operations

We propose a measure of non-classical correlations in bipartite quantum states based on local unitary operations. We prove the measure is non-zero if and only if the quantum discord is non-zero; this is achieved via a new characterization of zero discord states in terms of the state's correlation matrix. Moreover, our scheme can be extended to ensure the same relationship holds even with a generalized version of quantum discord in which higher-rank projective measurements are allowed. We next derive a closed form expression for our scheme in the cases of Werner states and (2 x N)-dimensional systems. The latter reveals that for (2 x N)-dimensional states, our measure reduces to the geometric discord [Dakic et al., PRL 105, 2010]. A connection to the CHSH inequality is shown. We close with a characterization of all maximally non-classical, yet separable, (2 x N)-dimensional states of rank at most two (with respect to our measure).
Is it feasible to outsource the remote monitoring of implantable cardiac defibrillators in a large tertiary hospital?

Abstract Aim To provide a detailed description of the workflow at our telecardiology centre and to analyse the workload of real-world remote monitoring with the aim to assess the feasibility to outsource this service. Methods A retrospective analysis was conducted on the telecardiology service provided at the University Hospitals of Leuven by extracting patient demographic data, general time usage and detailed information about the type of remote contacts. 10,869 contacts in 948 patients have been included. A 2-week prospective study was conducted on the same service by documenting and monitoring every action performed by specialised nurses when analysing and solving remote monitoring transmissions. 337 contacts in 262 patients were collected during this period. Results Both analyses indicated similar numbers of events and interventions. Unplanned transmissions were more challenging and required more interventions than planned transmissions. Relatively little time (retrospective median: 1.83 min; prospective median: 1.56 min, per event) was spent on incoming non-actionable ‘normal’ transmissions (retrospective: 46%; prospective: 40% of all events). Retrospectively 54% and prospectively 60% of transmissions showed abnormalities and were responsible for most of the time expended. Disease-related issues were the most frequent cause for these ‘abnormal’ alerts. Contacting patients and physicians were key interventions undertaken. Interaction initiated by patients mainly involved the installation process (42%) and bedside monitoring problems (32%). Conclusion External data centres could deal with 40% of the transmissions, but the decline in workload would be negligible for the in-hospital remote monitoring team, because very little time is spent dealing with the many ‘non-event’ transmissions whereas most of the time is spent solving clinical problems. Providing sufficient resources and optimising communication protocols is necessary to aid in managing the workload of the remote monitoring team. Implications for practice Contacting patients and physicians are key interventions for specialist nurses in remote monitoring centres. Detailed timing confirmed that most time was spent on relevant disease-related clinical problems. Despite dealing with ∼40% of transmissions, outsourcing to external data centres would decrease the workload only by 15–25%. Patient initiated contacts with questions concerning remote monitoring form a high burden and should be countered by scaling the service and creating communication protocols.
Discovery of rosin-based acylhydrazone derivatives as potential antifungal agents against rice Rhizoctonia solani for sustainable crop protection.

BACKGROUND The use of fungicides to protect crops from diseases is an effective method, and the novel environmental-friendly plant-derived fungicides with enhanced performance and low toxicity are urgent requirements for sustainable agriculture. RESULTS Two kinds of rosin-based acylhydrazone compounds were designed and prepared. Based on the antifungal activity assessment against Rhizoctonia solani, Fusarium oxysporum, Phytophthora capsici, Sclerotinia sclerotiorum, and Botrytis cinerea, acylhydrazone derivatives containing thiophene ring were screened, and they showed an inhibitory effect on rice R. solani. Among these, Compound 4n, with an electron-withdrawing group on the benzene ring structure attached to the thiophene ring, showed optimal activity, and the EC50 value was 0.981 mg/L, which was lower than that of carbendazim. Furthermore, it was indicated that 4n could affect the mycelial morphology, cell membrane permeability and microstructure, cause the generation of ROS in fungal cells and damage the nucleus and mitochondrial physiological function, resulting in the cell death of R. solani. Meanwhile, Compound 4n exhibited a better therapeutic effect on in vivo rice plants. However, the induction activity of 4n on the defense enzyme in rice leaf sheaths showed that 4n stimulates the initial resistance of rice plants by removing active oxygen, thereby protecting the cell membrane or enhancing the strength of the cell wall. Through the quantitative structure-activity relationship study, the quantitative chemical and electrostatic descriptors significantly affect the binding of 4n with the receptor, which improves its antifungal activity. CONCLUSION This study provides a basis for exploiting potential rosin-based fungicides in promoting sustainable crop protection. This article is protected by copyright. All rights reserved.
Age Determination Method of Pre-Main Sequence Stars with High-Resolution I-Band Spectroscopy

We present a new method for determining the age of late-K type pre-main sequence (PMS) stars by deriving their surface gravity from high-resolution I-band spectroscopy. Since PMS stars contract as they evolve, age can be estimated from surface gravity. We used the equivalent width ratio (EWR) of nearby absorption lines to create a surface gravity diagnostic of PMS stars that is free of uncertainties due to veiling. The ratios of Fe (818.67nm and 820.49nm) and Na (818.33nm and 819.48nm) absorption lines were calculated for giants, main-sequence stars, and weak-line T Tauri stars. Effective temperatures were nearly equal across the sample. The Fe to Na EWR (Fe/Na) decreases significantly with increasing surface gravity, denoting that Fe/Na is a desirable diagnostic for deriving the surface gravity of pre-main sequence stars. The surface gravity of PMS stars with 0.8 solar mass is able to be determined with an accuracy of 0.1-0.2, which conducts the age of PMS stars within a factor of 1.5, in average.
GHASP: an H alpha kinematic survey of spiral galaxies - X. Surface photometry, decompositions and the Tully-Fisher relation in the R-c band

We present R-c-band surface photometry for 170 of the 203 galaxies in GHASP, the Gassendi H-alpha survey of spirals, a sample of late-type galaxies for which high-resolution Fabry-Perot H alpha maps have previously been obtained. Our data set is constructed using new R-c-band observations taken at the Observatoire de Haute-Provence, supplemented with Sloan Digital Sky Survey archival data, obtained with the purpose of deriving homogeneous photometric profiles and parameters. Our results include R-c-band surface brightness profiles for 170 galaxies and ugriz profiles for 108 of these objects. We catalogue several parameters of general interest for further reference, such as total magnitude, effective radius and isophotal parameters (magnitude, position angle, ellipticity and inclination). We also perform a structural decomposition of the surface brightness profiles using a multi-component method to separate discs from bulges and bars, and to observe the main scaling relations involving luminosities, sizes and maximum velocities. We determine the R-c-band Tully-Fisher relation using maximum velocities derived solely from H alpha rotation curves for a sample of 80 galaxies, resulting in a slope of -8.1 +/- 0.5, zero-point of -3.0 +/- 1.0 and an estimated intrinsic scatter of 0.28 +/- 0.07. We note that, unlike the Tully-Fisher relation in the near-infrared derived for the same sample, no change in the slope of the relation is seen at the low-mass end (for galaxies with V-max \textless 125 km s(-1)). We suggest that this different behaviour of the Tully-Fisher relation (with the optical relation being described by a single power law while the near-infrared has two), may be caused by differences in the stellar mass-to-light ratio for galaxies with V-max \textless 125 km s(-1).
Factors associated with comprehensive knowledge of antenatal care and attitude towards its uptake among women delivered at home in rural Sehala Seyemit district, northern Ethiopia: A community-based cross-sectional study

Background Despite the current sustainable development goal period (i.e. SDG 3), the prevention of maternal and neonatal mortality is not satisfactory in Ethiopia. Keeping women knowledgeable about antenatal care and maintaining a positive attitude towards its uptake, particularly in the marginalized rural community is crucial. However, evidence regarding the knowledge and attitude of women towards antenatal care uptake is scarce. Therefore, this study aimed to assess factors affecting comprehensive knowledge of antenatal care and attitude towards its uptake among women delivered at home in rural Sehala Seyemit district, northern Ethiopia. Methods A community-based cross-sectional study was conducted from September 1st to October 15th, 2020. A multi-stage sampling technique was used to select 653 women. The data were collected using a semi-structured interview guide. Data were entered into EPI INFO 7.1. 2 and analyzed by SPSS version 25. Both bivariable and multivariable logistic regression analyses were undertaken to identify factors associated with women’s knowledge of antenatal care and attitude towards its uptake. The level of significant association in the multivariable analysis was determined based on a p-value of < 0.05. Results Women’s knowledge of antenatal care and positive attitude towards its uptake was 56.5% and 75.2%, respectively. Older age (AOR = 7.2; 95% CI: 3.43, 15.1), media exposure (AOR = 3.69; 95% CI: 2.41, 5.65), history of abortion (AOR = 11.6; 95% CI: 3.3, 14.6), time to reach health facility (AOR = 4.58; 95% CI: 3.05, 6.88), and history of obstetric danger signs (AOR = 7.3; 95% CI: 3.92, 13.64) were factors significantly associated with knowledge of antenatal care. Furthermore, higher decision-making power (AOR = 8.3; 95% CI: 4.8, 13.83), adequate knowledge of antenatal care (AOR = 2.2; 95% CI: 1.26, 3.71), delivery attended by health extension workers (AOR = 2.3; 95% CI: 1.1, 5.1), and media exposure (AOR = 2.27; 95% CI: 1.30, 3.97) were predictors of a favorable attitude towards antenatal care utilization. Conclusion Although the majority of women in the present study had a favorable attitude towards antenatal care uptake, their knowledge level was inadequate. Strengthening access to transportation, mass media, involvement in household decision-making, and encouraging women to deliver at a health facility by a skilled provider may increase women’s knowledge and attitude towards antenatal care uptake, thereby improving maternal healthcare service uptake.
Effects of land clearing for agriculture on soil organic carbon stocks in drylands: A meta‐analysis

Agricultural activities have been expanding globally with the pressure to provide food security to the earth's growing population. These agricultural activities have profoundly impacted soil organic carbon (SOC) stocks in global drylands. However, the effects of clearing natural ecosystems for cropland (CNEC) on SOC are uncertain. To improve our understanding of carbon emissions and sequestration under different land uses, it is necessary to characterize the response patterns of SOC stocks to different types of CNEC. We conducted a meta‐analysis with mixed‐effect model based on 873 paired observations of SOC in croplands and adjacent natural ecosystems from 159 individual studies in global drylands. Our results indicate that CNEC significantly (p < .05) affects SOC stocks, resulting from a combination of natural land clearing, cropland management practices (fertilizer application, crop species, cultivation duration) and the significant negative effects of initial SOC stocks. Increases in SOC stocks (in 1 m depth) were found in croplands which previously natural land (deserts and shrublands) had low SOC stocks, and the increases were 278.86% (95% confidence interval, 196.43%–361.29%) and 45.38% (26.53%–62.23%), respectively. In contrast, SOC stocks (in 1 m depth) decreased by 24.11% (18.38%–29.85%) and 10.70% (1.80%–19.59%) in clearing forests and grasslands for cropland, respectively. We also established the general response curves of SOC stocks change to increasing cultivation duration, which is crucial for accurately estimating regional carbon dynamics following CNEC. SOC stocks increased significantly (p < .05) with high long‐term fertilizer consumption in cleared grasslands with low initial SOC stocks (about 27.2 Mg ha−1). The results derived from our meta‐analysis could be used for refining the estimation of dryland carbon dynamics and developing SOC sequestration strategies to achieve the removal of CO2 from the atmosphere.
Experiences and challenges faced by patients with COVID-19 who were hospitalised and participated in a randomised controlled trial: a qualitative study

Objectives As part of a randomised controlled trial, this qualitative study aimed to identify experiences and challenges of hospitalised patients with COVID-19 during illness and treatment (objective 1: COVID-19-related perspectives; objective 2: trial participation-related perspectives). Design Semistructured interviews following a prespecified interview guide, transcribed verbatim and analysed in accordance with the grounded theory process. Investigator triangulation served to ensure rigour of the analysis. Setting Interviews were embedded in a multicentre, randomised, active-controlled, open-label platform trial testing efficacy and safety of experimental therapeutics for patients with COVID-19 (Austrian Corona Virus Adaptive Clinical Trial). Participants 20 patients (60±15 years) providing 21 interviews from 8 June 2020 to 25 April 2021. Results Qualitative data analysis revealed four central themes with subthemes. Theme 1, ‘A Severe Disease’, related to objective 1, was characterised by subthemes ‘symptom burden’, ‘unpredictability of the disease course’, ‘fear of death’ and ‘long-term aftermaths with lifestyle consequences’. Theme 2, ‘Saved and Burdened by Hospitalization’, related to objective 1, comprised patients describing their in-hospital experience as ‘safe haven’ versus ‘place of fear’, highlighting the influence of ‘isolation’. Theme 3, ‘Managing One’s Own Health’, related to objective 1, showed how patients relied on ‘self-management’ and ‘coping’ strategies. Theme 4, ‘Belief in Medical Research’, related to objective 2, captured patients’ ‘motivation for study participation’, many expressing ‘information gaps’ and ‘situational helplessness’ in response to study inclusion, while fewer mentioned ‘therapy side-effects’ and provided ‘study reflection’. Investigator triangulation with an expert focus group of three doctors who worked at the study centre confirmed the plausibility of these results. Conclusions Several of the identified themes (2, 3, 4) are modifiable and open for interventions to improve care of patients with COVID-19. Patient-specific communication and information is of utmost importance during clinical trial participation, and was criticised by participants of the present study. Disease self-management should be actively encouraged. Trial registration number NCT04351724.