Miracle-dz/UniFAR-FTUs huggingface dataset:
Headcase is a Repressor of Lamellocyte Fate in Drosophila melanogaster

Due to the evolutionary conservation of the regulation of hematopoiesis, Drosophila provides an excellent model organism to study blood cell differentiation and hematopoietic stem cell (HSC) maintenance. The larvae of Drosophila melanogaster respond to immune induction with the production of special effector blood cells, the lamellocytes, which encapsulate and subsequently kill the invader. Lamellocytes differentiate as a result of a concerted action of all three hematopoietic compartments of the larva: the lymph gland, the circulating hemocytes, and the sessile tissue. Within the lymph gland, the communication of the functional zones, the maintenance of HSC fate, and the differentiation of effector blood cells are regulated by a complex network of signaling pathways. Applying gene conversion, mutational analysis, and a candidate based genetic interaction screen, we investigated the role of Headcase (Hdc), the homolog of the tumor suppressor HECA in the hematopoiesis of Drosophila. We found that naive loss-of-function hdc mutant larvae produce lamellocytes, showing that Hdc has a repressive role in effector blood cell differentiation. We demonstrate that hdc genetically interacts with the Hedgehog and the Decapentaplegic pathways in the hematopoietic niche of the lymph gland. By adding further details to the model of blood cell fate regulation in the lymph gland of the larva, our findings contribute to the better understanding of HSC maintenance.
Outpatient Cancer Care Delivery in the Context of E-Oncology: A French Perspective on “Cancer outside the Hospital Walls”

In oncology, the treatment of patients outside of hospitals has become imperative due to an increasing number of patients who are older and live longer, along with issues such as medical desertification, oncologist hyperspecialization, and difficulties in financing mounting health expenditures. Treatments have become less “invasive”, with greater precision and efficiency. Patients can therefore receive most of their care outside of hospitals. The development of e-health can address these new imperatives. In this letter, we describe the different e-health tools and their potential clinical impacts in oncology, as already reported at every level of care, including education, prevention, diagnosis, treatment, and monitoring. A few randomized studies have yet demonstrated the clinical benefit. We also comment on issues and limits of “cancer outside the hospital walls” from the point of view of patients, health care professionals, health facilities, and public authorities. Care providers in hospitals and communities will have to adapt to these changes within well-coordinated networks in order to better meet patient expectations regarding increasing education and personalizing management. Ultimately, controlled studies should aim to definitively demonstrate areas of interest, benefits, and incentives, for not only patients, but also caregivers (formal and informal) and health care providers, health care facilities, and the nation.
Continued attendance for paediatric weight management: A multicentre, qualitative study of parents' reasons and facilitators

Although prolonged engagement in paediatric weight management (PWM) is associated with positive treatment outcomes, little is currently known about enablers of long‐term programme attendance. The purpose of our study was to explore families' reasons for and facilitators of their continued attendance at health services for PWM. Semi‐structured, individual interviews were conducted with parents of children (10‐17 year old; body mass index ≥85th percentile) who completed the active phase of treatment in one of four Canadian multidisciplinary clinics for PWM. Interview data were recorded digitally, transcribed verbatim and analysed thematically. Parents' (n = 40) reasons for continued clinic attendance included ongoing concerns (eg, parental concern about their child's health), actual and expected benefits from treatment (eg, lifestyle improvements) and perceived quality of care (eg, structured, comprehensive, tailored health services). Several logistical and motivational factors contributed to continued attendance, including flexible work schedules, flexible appointment times, financial resources and children's motivation for treatment. Helping families address treatment barriers and ensuring that weight management services meet families' treatment expectations are promising strategies to enhance retention in PWM to optimize health outcomes.
Habitual versus Goal-directed Action Control in Parkinson Disease

This study presents the first direct investigation of the hypothesis that dopamine depletion of the dorsal striatum in mild Parkinson disease leads to impaired stimulus–response habit formation, thereby rendering behavior slow and effortful. However, using an instrumental conflict task, we show that patients are able to rely on direct stimulus–response associations when a goal-directed strategy causes response conflict, suggesting that habit formation is not impaired. If anything our results suggest a disease severity–dependent deficit in goal-directed behavior. These results are discussed in the context of Parkinson disease and the neurobiology of habitual and goal-directed behavior.
Stepwise activation mechanism of the scramblase nhTMEM16 revealed by cryo-EM

Scramblases catalyze the movement of lipids between both leaflets of a bilayer. Whereas the X-ray structure of the protein nhTMEM16 has previously revealed the architecture of a Ca2+-dependent lipid scramblase, its regulation mechanism has remained elusive. Here, we have used cryo-electron microscopy and functional assays to address this question. Ligand-bound and ligandfree conformations of nhTMEM16 in detergents and lipid nanodiscs illustrate the interactions with its environment and they reveal the conformational changes underlying its activation. In this process, Ca2+-binding induces a stepwise transition of the catalytic subunit cavity, converting a closed cavity that is shielded from the membrane in the absence of ligand, into a polar furrow that becomes accessible to lipid headgroups in the ligand-bound state. Additionally, our structures demonstrate how nhTMEM16 distorts the membrane at both entrances of the subunit cavity, thereby decreasing the energy barrier for lipid movement.
Interoperable and scalable data analysis with microservices: applications in metabolomics

Abstract Motivation Developing a robust and performant data analysis workflow that integrates all necessary components whilst still being able to scale over multiple compute nodes is a challenging task. We introduce a generic method based on the microservice architecture, where software tools are encapsulated as Docker containers that can be connected into scientific workflows and executed using the Kubernetes container orchestrator. Results We developed a Virtual Research Environment (VRE) which facilitates rapid integration of new tools and developing scalable and interoperable workflows for performing metabolomics data analysis. The environment can be launched on-demand on cloud resources and desktop computers. IT-expertise requirements on the user side are kept to a minimum, and workflows can be re-used effortlessly by any novice user. We validate our method in the field of metabolomics on two mass spectrometry, one nuclear magnetic resonance spectroscopy and one fluxomics study. We showed that the method scales dynamically with increasing availability of computational resources. We demonstrated that the method facilitates interoperability using integration of the major software suites resulting in a turn-key workflow encompassing all steps for mass-spectrometry-based metabolomics including preprocessing, statistics and identification. Microservices is a generic methodology that can serve any scientific discipline and opens up for new types of large-scale integrative science. Availability and implementation The PhenoMeNal consortium maintains a web portal (https://portal.phenomenal-h2020.eu) providing a GUI for launching the Virtual Research Environment. The GitHub repository https://github.com/phnmnl/ hosts the source code of all projects. Supplementary information Supplementary data are available at Bioinformatics online.
Cross-talk between N-terminal and C-terminal domains in stromal interaction molecule 2 (STIM2) determines enhanced STIM2 sensitivity

Store-operated Ca2+ entry (SOCE) is a ubiquitous pathway for Ca2+ influx across the plasma membrane (PM). SOCE is mediated by the endoplasmic reticulum (ER)-associated Ca2+-sensing proteins stromal interaction molecule 1 (STIM1) and STIM2, which transition into an active conformation in response to ER Ca2+ store depletion, thereby interacting with and gating PM-associated ORAI1 channels. Although structurally homologous, STIM1 and STIM2 generate distinct Ca2+ signatures in response to varying strengths of agonist stimulation. The physiological functions of these Ca2+ signatures, particularly under native conditions, remain unclear. To investigate the structural properties distinguishing STIM1 and STIM2 activation of ORAI1 channels under native conditions, here we used CRISPR/Cas9 to generate STIM1−/−, STIM2−/−, and STIM1/2−/− knockouts in HEK293 and colorectal HCT116 cells. We show that depending on cell type, STIM2 can significantly sustain SOCE in response to maximal store depletion. Utilizing the SOCE modifier 2-aminoethoxydiphenyl borate (2-APB), we demonstrate that 2-APB–activated store-independent Ca2+ entry is mediated exclusively by endogenous STIM2. Using variants that either stabilize or disrupt intramolecular interactions of STIM C termini, we show that the increased flexibility of the STIM2 C terminus contributes to its selective store-independent activation by 2-APB. However, STIM1 variants with enhanced flexibility in the C terminus failed to support its store-independent activation. STIM1/STIM2 chimeric constructs indicated that coordination between N-terminal sensitivity and C-terminal flexibility is required for specific store-independent STIM2 activation. Our results clarify the structural determinants underlying activation of specific STIM isoforms, insights that are potentially useful for isoform-selective drug targeting.
Short-term exercise training reduces glycaemic variability and lowers circulating endothelial microparticles in overweight and obese women at elevated risk of type 2 diabetes

Abstract Exercise is recognized as a frontline therapy for the prevention and treatment of type 2 diabetes (T2D) but the optimal type of exercise is not yet determined. We compared the effects of high-intensity interval training (HIIT) with moderate-intensity continuous training (MICT) for improvement of continuous glucose monitoring (CGM)-derived markers of glycaemic variability, and biomarkers of endothelial cell damage (CD31+ and CD62+ endothelial microparticles (EMPs)) within a population at elevated risk of developing T2D. Fifteen inactive overweight or obese women were randomized to 2 weeks (10-sessions) of progressive HIIT (n = 8, 4–10X 1-min @ ∼90% peak heart rate, 1-min rest periods) or MICT (n = 7, 20–50 min of continuous activity at ∼65% peak heart rate). Prior and three days post-training, fasting blood samples were collected. Both HIIT and MICT improved glycaemic variability as measured by CGM standard deviation (HIIT: 0.82 ± 0.39 vs. 0.72 ± 0.33 mmol/L; MICT: 0.82 ± 0.19 vs. 0.62 ± 0.16 mmol/L, pre vs. post) and mean amplitude of glycaemic excursions (MAGE; HIIT: 1.98 ± 0.81 vs. 1.41 ± 0.90; MICT; 1.98 ± 0.43 vs. 1.65 ± 0.48, pre vs. post) with no difference between groups. CD62+ EMPs were lower following HIIT (187.7 ± 65 vs. 174.9 ± 55, pre vs. post) and MICT (170 ± 60 vs. 160.3 ± 59, pre vs. post) with no difference between groups. There was no change in 24-h mean glucose or CD31+ EMPs. Two weeks of both HIIT or MICT similarly decreased glycaemic variability and CD62+ EMPs in overweight/obese women at elevated risk of T2D.
Increased Risk of Cardiovascular Diseases in Female Rosacea Patients: A Nested Case-control Study.

1https://www.medicaljournals. se/acta/content/abstract/10.2340/00015555-3167 Rosacea is a chronic inflammatory disease with a prevalence varying between 1 and 20% and is the highest in fair-skinned Europeans (1). The appearance of rosacea differs between the sexes; there is a female predominance and the onset of the disease is earlier in females than in males (1). Of the 4 subtypes of rosacea (erythematoteleangiectatic, papulopustular, ocular and phymatotic) the erythematoteleangiectatic type is more common in females and the phymatous type in males (2). There is a rising consensus that rosacea is not only limited to the skin but is a chronic systemic inflammatory disease. Several systemic diseases have recently been shown to be associated with rosacea (3). However, it is disputed whether rosacea is associated with cardiovascular (CV) diseases. The risk for comorbidities in rosacea has also been suggested to differ between sexes. Egeberg et al. found that rosacea is associated with type 1 diabetes, celiac disease, multiple sclerosis and rheumatoid arthritis particularly in females (4). The aim of this study was to clarify the CV risk factors in rosacea patients by comprehensively studying the CV risk profile of middle-aged patients with rosacea.
Nanosecond-Laser Generation of Nanoparticles in Liquids: From Ablation through Bubble Dynamics to Nanoparticle Yield

A comprehensive picture of the nanosecond-laser generation of colloidal nanoparticles in liquids is nowadays the demand of their high-throughput industrial fabrication for diverse perspective biomedical, material science, and optoelectronic applications. In this study, using silicon as an example, we present a self-consistent experimental visualization and theoretical description of key transient stages during nanosecond-laser generation of colloidal nanoparticles in liquids: plasma-mediated injection of ablated mass into the liquid and driving the vapor bubble, finalized by the colloid appearance in the liquid. The explored fundamental transient stages envision the basic temporal and spatial scales, as well as laser parameter windows, for the demanded high-throughput nanosecond-laser generation of colloidal nanoparticles in liquids.
MyTraces

Most of the existing work concerning the analysis of emotional states and mobile phone interaction has been based on correlation analysis. In this paper, for the first time, we carry out a causality study to investigate the causal links between users’ emotional states and their interaction with mobile phones, which could provide valuable information to practitioners and researchers. The analysis is based on a dataset collected in-the-wild. We recorded 5,118 mood reports from 28 users over a period of 20 days. Our results show that users’ emotions have a causal impact on different aspects of mobile phone interaction. On the other hand, we can observe a causal impact of the use of specific applications, reflecting the external users’ context, such as socializing and traveling, on happiness and stress level. This study has profound implications for the design of interactive mobile systems since it identifies the dimensions that have causal effects on users’ interaction with mobile phones and vice versa. These findings might lead to the design of more effective computing systems and services that rely on the analysis of the emotional state of users, for example for marketing and digital health applications.
Drift happens: Molecular genetic diversity and differentiation among populations of jewelweed (Impatiens capensis Meerb.) reflect fragmentation of floodplain forests

Landscape features often shape patterns of gene flow and genetic differentiation in plant species. Populations that are small and isolated enough also become subject to genetic drift. We examined patterns of gene flow and differentiation among 12 floodplain populations of the selfing annual jewelweed (Impatiens capensis Meerb.) nested within four river systems and two major watersheds in Wisconsin, USA. Floodplain forests and marshes provide a model system for assessing the effects of habitat fragmentation within agricultural/urban landscapes and for testing whether rivers act to genetically connect dispersed populations. We generated a panel of 12,856 single nucleotide polymorphisms and assessed genetic diversity, differentiation, gene flow, and drift. Clustering methods revealed strong population genetic structure with limited admixture and highly differentiated populations (mean multilocus FST = 0.32, FST’ = 0.33). No signals of isolation by geographic distance or environment emerged, but alleles may flow along rivers given that genetic differentiation increased with river distance. Differentiation also increased in populations with fewer private alleles (R2 = 0.51) and higher local inbreeding (R2 = 0.22). Populations varied greatly in levels of local inbreeding (FIS = 0.2–0.9) and FIS increased in more isolated populations. These results suggest that genetic drift dominates other forces in structuring these Impatiens populations. In rapidly changing environments, species must migrate or genetically adapt. Habitat fragmentation limits both processes, potentially compromising the ability of species to persist in fragmented landscapes.
Mechanisms linking socioeconomic status to smoking cessation: a structural equation modeling approach.

OBJECTIVE Although there has been a socioeconomic gradient in smoking prevalence, cessation, and disease burden for decades, these disparities have become even more pronounced over time. The aim of the current study was to develop and test a conceptual model of the mechanisms linking socioeconomic status (SES) to smoking cessation. DESIGN The conceptual model was evaluated using a latent variable modeling approach in a sample of 424 smokers seeking treatment (34% African American; 33% Latino; 33% White). Hypothesized mechanisms included social support, neighborhood disadvantage, negative affect/stress, agency, and craving. MAIN OUTCOME MEASURE The primary outcome was Week 4 smoking status. RESULTS As was hypothesized, SES had significant direct and indirect effects on cessation. Specifically, neighborhood disadvantage, social support, negative affect/stress, and agency mediated the relation between SES and smoking cessation. A multiple group analysis indicated that the model was a good fit across racial/ethnic groups. CONCLUSION The present study yielded one of the more comprehensive models illuminating the specific mechanisms that link SES and smoking cessation. Policy, community, and individual-level interventions that target low SES smokers and address the specific pathways identified in the current model could potentially attenuate the impact of SES on cessation.
Harnessing the potential of integrated systematics for conservation of taxonomically complex, megadiverse plant groups

The value of natural history collections for conservation science research is increasingly recognized, despite their well‐documented limitations in terms of taxonomic, geographic, and temporal coverage. Specimen‐based analyses are particularly important for tropical plant groups for which field observations are scarce and potentially unreliable due to high levels of diversity‐amplifying identification challenges. Specimen databases curated by specialists are rich sources of authoritatively identified, georeferenced occurrence data, and such data are urgently needed for large genera. We compared entries in a monographic database for the large Neotropical genus Myrcia in 2007 and 2017. We classified and quantified differences in specimen records over this decade and determined the potential impact of these changes on conservation assessments. We distinguished misidentifications from changes due to taxonomic remodeling and considered the effects of adding specimens and georeferences. We calculated the potential impact of each change on estimates of extent of occurrence (EOO), the most frequently used metric in extinction‐risk assessments of tropical plants. We examined whether particular specimen changes were associated with species for which changes in EOO over the decade were large enough to change their conservation category. Corrections to specimens previously misidentified or lacking georeferences were overrepresented in such species, whereas changes associated with taxonomic remodeling (lumping and splitting) were underrepresented. Among species present in both years, transitions to less threatened status outnumbered those to more threatened (8% vs 3%, respectively). Species previously deemed data deficient transitioned to threatened status more often than to not threatened (10% vs 7%, respectively). Conservation scientists risk reaching unreliable conclusions if they use specimen databases that are not actively curated to reflect changing knowledge.
High prevalence of imipenem-resistant and metallo-beta-lactamase-producing Pseudomonas aeruginosa in the Burns Hospital in Tunisia: detection of a novel class 1 integron

Pseudomonas aeruginosa is one of the most important causes of nosocomial infections, and its eradication is very difficult due to its multidrug resistance. The objective of the present study was to characterize the metallo-beta-lactamases (MBLs), integrons, OprD modifications and virulence factors of P. aeruginosa strains isolated from burn patients and to analyze their genetic relatedness by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Sixty-seven P. aeruginosa isolates were recovered from different clinical samples of burn patients hospitalized in the Intensive Care Burn Unit of the Centre de Traumatologie et des Grands Brulés (Ben Arous, Tunisia), and MBLs and alterations in porin OprD were analyzed among imipenem-resistant isolates. Class 1 and 2 integrons were studied by PCR and sequencing of corresponding variable regions. The presence of eight genes involved in the virulence of P. aeruginosa was investigated by PCR. Fourteen of the 36 imipenem-resistant P. aeruginosa (IRPA) isolates (38.8%) were MBLs producers and harbored the blaVIM-2 gene, in all cases included into class 1 integrons. A new class 1 integron was identified (intI1-blaOXA-10-aadB-blaVIM-2-aadB-blaOXA-10). Five sequence types were detected among IRPA isolates: ST1, ST112, ST238, ST308 and ST395. P. aeruginosa is a major nosocomial pathogen in patients suffering burns, and the spreading of multidrugs resistant and MBL-producing isolates should be controlled in burn units. Moreover, the implantation of infection control guidelines is crucial to decrease the morbidity and mortality of nosocomial infections due to multidrug resistant P. aeruginosa.