Miracle-dz/UniFAR-FTUs huggingface dataset:
Listeria monocytogenes triggers noncanonical autophagy upon phagocytosis, but avoids subsequent growth-restricting xenophagy

Significance Autophagy mediates the routing of cytoplasmic components to degradative membrane-bound compartments. During infection by intracellular pathogens, autophagy proteins orchestrate several antimicrobial responses by marking pathogen-containing vacuoles and protecting the host cytosol from invaders. However, intracellular pathogens such as Listeria monocytogenes circumvent the autophagy machinery to promote pathogenesis. By combining bacterial and host mutants, we have dissected the role of two distinct autophagy-related processes in controlling L. monocytogenes growth in macrophages. Our results showed that L. monocytogenes is oblivious to the initial marking of its vacuole by autophagy proteins, but that subsequent autophagic targeting restricts bacterial growth in the host cytosol. We suggest that processes coordinated by the autophagy machinery constitute a multilayered network of cell-autonomous defenses. Xenophagy is a selective macroautophagic process that protects the host cytosol by entrapping and delivering microbes to a degradative compartment. Both noncanonical autophagic pathways and xenophagy are activated by microbes during infection, but the relative importance and function of these distinct processes are not clear. In this study, we used bacterial and host mutants to dissect the contribution of autophagic processes responsible for bacterial growth restriction of Listeria monocytogenes. L. monocytogenes is a facultative intracellular pathogen that escapes from phagosomes, grows in the host cytosol, and avoids autophagy by expressing three determinants of pathogenesis: two secreted phospholipases C (PLCs; PlcA and PlcB) and a surface protein (ActA). We found that shortly after phagocytosis, wild-type (WT) L. monocytogenes escaped from a noncanonical autophagic process that targets damaged vacuoles. During this process, the autophagy marker LC3 localized to single-membrane phagosomes independently of the ULK complex, which is required for initiation of macroautophagy. However, growth restriction of bacteria lacking PlcA, PlcB, and ActA required FIP200 and TBK1, both involved in the engulfment of microbes by xenophagy. Time-lapse video microscopy revealed that deposition of LC3 on L. monocytogenes-containing vacuoles via noncanonical autophagy had no apparent role in restricting bacterial growth and that, upon access to the host cytosol, WT L. monocytogenes utilized PLCs and ActA to avoid subsequent xenophagy. In conclusion, although noncanonical autophagy targets phagosomes, xenophagy was required to restrict the growth of L. monocytogenes, an intracellular pathogen that damages the entry vacuole.
Cryptic species and their utilization of indigenous and non-indigenous intermediate hosts in the acanthocephalan Polymorphus minutus sensu lato (Polymorphidae)

Abstract The bird-infecting acanthocephalan Polymorphus minutus has been suggested to comprise different lineages or even cryptic species using different intermediate hosts. To clarify this open question, we investigated Polymorphus cf. minutus cystacanths originating from amphipod intermediate hosts from 27 sites in Germany and France. Parasites and hosts were identified using integrated datasets (COI and/or morphology for hosts and COI + ITS1-5.8S-ITS2 for parasites). Mitochondrial and nuclear data (ITS1) strongly support the existence of three cryptic species in Polymorphus cf. minutus (type 1-3). These three types reveal a high degree of intermediate host specificity, with Polymorphus type 1 only encountered in Gammarus fossarum type B, Polymorphus type 2 in Echinogammarus sp. and Echinogammarus berilloni, and Polymorphus type 3 in Gammarus pulex and Gammarus roeselii. Our results point to a so far neglected cryptic diversity of the genus Polymorphus in Central Europe. Furthermore, Polymorphus type 2 is most likely a non-native parasite in Germany that co-invaded with E. berilloni from the Mediterranean area. Potentially, type 3 originates from South-East Europe and migrated to Germany by G. roeselii, where it might have captured G. pulex as an intermediate host. Therefore, our findings can be seen in the context of ecological globalization in terms of the anthropogenic displacement of intermediate hosts and its impact on the genetic divergence of the parasites.
Parenting challenges in the setting of terminal illness: a family-focused perspective

Purpose of reviewIn the advanced stages of illness, families with dependent children experience disruption across all dimensions of family life. The need for family support during palliative care is well recognized, yet little is understood about how parents and their children navigate these difficult circumstances. This review summarizes the current body of research on parenting challenges in advanced cancer. Recent findingsTo date, the study of parental cancer has focused predominantly on the early stages of disease and its impact on children and adolescents. Less is known about how families with minor children prepare for parental loss. Evidence suggests that having dependent children influences parents’ treatment decisions at the end of life, and that a central concern for children and parents is optimizing time spent together. Parents may feel an urgency to engage in accelerated parenting, and maintaining normalcy remains a consistent theme for the ill and healthy parent alike. There is a growing evidence base affirming the importance of responsive communication prior to death. SummaryAdvancing knowledge about the parenting experience at the end of life is critical for ensuring effective support to the entire family, as it accommodates and prepares for the loss of a vital member.
Autoimmunity in Dry Eye Is Due to Resistance of Th17 to Treg Suppression1

Dry eye disease (DED), an inflammatory autoimmune disorder affecting the ocular surface, degrades visual performance and the quality of life of >10 million people in the United States alone. The primary limitation in the effective treatment of DED is an incomplete understanding of its specific cellular and molecular pathogenic elements. Using a validated mouse model of DED, herein we functionally characterize the different T cell subsets, including regulatory T cells (Tregs) and pathogenic effector T cells, and determine their contribution to the pathogenesis of DED. Our data demonstrate the presence of dysfunctional Tregs and the resistance of pathogenic T cells, particularly Th17 cells, to Treg suppression in DED. In addition, we clearly show that in vivo blockade of IL-17 significantly reduces the severity and progression of disease, which is paralleled by a reduction in the expansion of Th17 cells and restoration of Treg function. Our findings elucidate involvement of a previously unknown pathogenic T cell subset (Th17) in DED that is associated specifically with Treg dysfunction and disease pathogenesis and suggest a new target for dry eye therapy.
When acting as a reproductive barrier for sympatric speciation, hybrid sterility can only be primary

Animal gametes unite to form a zygote that develops into an adult with gonads that, in turn, produce gametes. Interruption of this germinal cycle by prezygotic or postzygotic reproductive barriers can result in two cycles, each with the potential to evolve into a new species. When the speciation process is complete, members of each species are fully reproductively isolated from those of the other. During speciation a primary barrier may be supported and eventually superceded by a later-appearing secondary barrier. For those holding certain cases of prezygotic isolation to be primary (e.g. elephant cannot copulate with mouse), the onus is to show that they had not been preceded over evolutionary time by periods of postzygotic hybrid inviability (genically determined) or sterility (genically or chromosomally determined). Likewise, the onus is upon those holding cases of hybrid inviability to be primary (e.g. Dobzhansky–Muller epistatic incompatibilities) to show that they had not been preceded by periods, however brief, of hybrid sterility. The latter, when acting as a sympatric barrier causing reproductive isolation, can only be primary. In many cases, hybrid sterility may result from incompatibilities between parental chromosomes that attempt to pair during meiosis in the gonad of their offspring (Winge-Crowther-Bateson incompatibilities). While such incompatibilities have long been observed on a microscopic scale, there is growing evidence for a role of dispersed finer DNA sequence differences (i.e. in base k-mers).
Parallel or event-driven goal setting mechanism in Petri net based models of expert decision behaviour

Decisions and actions produced by computer users (observed process) contain much information about their mental models, individual problem solving strategy and underlying decision structure for a given task. Our tool AMME analyses observed processes and automatically extracts a Petri net description of the task dependent decision structure (logical structure). This net is extended by goal setting structures (modelling) and executed (simulated process). The aim is functional equivalence between observed and simulated processes. Two modelling strategies, event-driven and parallel goal setting, are presented.
A Metric for Comparing Relational Descriptions

Relational models are frequently used in high-level computer vision. Finding a correspondence between a relational model and an image description is an important operation in the analysis of scenes. In this paper the process of finding the correspondence is formalized by defining a general relational distance measure that computes a numeric distance between any two relational descriptions-a model and an image description, two models, or two image descriptions. The distance measure is proved to be a metric, and is illustrated with examples of distance between object models. A variant measure used in our past studies is shown not to be a metric.
A new triterpenoid saponin and an oligosaccharide isolated from the fruits of Sapindus mukorossi

A new triterpenoid saponin (1) and a new oligosaccharide (2), together with three known saponins (3–5), have been isolated from n-BuOH extract of the fruits of Sapindus mukorossi Gaertn. The structures were elucidated using detailed analysis of one- and two-dimensional nuclear magnetic resonance spectra along with their mass spectrometric data and the results of acid hydrolysis. Of the isolated compounds 1 and 3–5 displayed cytotoxic effects against human cancer cell lines in A-549 (lung carcinoma), MDA-231 (breast carcinoma) and PC-3 (prostatic carcinoma).
A phosphoinositide-specific phospholipase C pathway elicits stress-induced Ca2+ signals and confers salt tolerance to rice.

In animal cells, phospholipase C (PLC) isoforms predominantly hydrolyze phosphatidylinositol-4,5-biphosphates [PtdIns(4,5)P2 ] into the second messengers diacylglycerol (DAG) and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3 ] to regulate diverse biological processes. By contrast, the molecular mechanisms and physiological significance of PLC signaling in plants still awaits full elucidation. Here, we identified a rice (Oryza sativa cv) PI-PLC, OsPLC1, which preferred to hydrolyze phosphatidylinositol-4-phosphate (PtdIns4P) and elicited stress-induced Ca2+ signals regulating salt tolerance. Analysis by ion chromatography revealed that the concentration of PtdIns4P was c. 28 times of that of PtdIns(4,5)P2 in shoots. OsPLC1 not only converted PtdIns(4,5)P2 but also - and even more efficiently - converted PtdIns4P into DAG and Ins(1,4,5)P3 in vitro and in vivo. Salt stress induced the recruitment of OsPLC1 from cytoplasm to plasma membrane, where it hydrolyzed PtdIns4P. The stress-induced Ca2+ signaling was dependent on OsPLC1, and the PLC-mediated Ca2+ signaling was essential for controlling Na+ accumulation in leaf blades, thus establishing whole plant salt tolerance. Our work identifies a conversion pathway and physiological function for PtdIns4P pools in rice and reveals the connection between phosphoinositides and Ca2+ signals mediated by PLC during salt stress responses.
Performance Evaluation of GMAW Welds for Four Advanced High Strength Steels

This paper investigates the characteristics of GMAW of various sheet steels grades ranging from HSLA, dual phase, to martensitic. From the arc welding point of view, the dual phase and martensitic steels behave similarly to conventional high strength steels. Regarding the properties of GMAW joints, the static and dynamic mechanical testing were conducted and compared along with the weld metal microhardness and microstructure. Results show that while the strength of the sheet steel weld, in general increases with the base material strength, Joint Efficiency, defined as the ratio of the strength of joint to the strength of the base metal, decreases with the increase of martensite fraction in the sheet steel. Martensitic steels, especially, exhibits reduced weld strength due to softening of the HAZ. However, fatigue strength of these steels is not adversely affected by the softened HAZ, and is insensitive to the strength of the steel. The hardness distribution in weldments can significantly affect the static performance of the welds and is dependent on the steel chemistry, steel processing and filler metal.
Effectiveness of Liquid-Based Cytology and Papanicolaou Tests in a Low Risk Population

OBJECTIVE To compare sensitivity an effectiveness of ThinPrep vs. Pap Test and determine whether the Hybrid Capture System II (HCII) for detection of human papillomavirus (HPV) could increase the sensitivity and effectiveness of cervical screening in a low risk population. STUDY DESIGN We present a comparative observer, blind, "split sample" study of ThinPrep and Papanicolaou staining in a population of 2026 consecutive women. RESULTS Conventional Papanicolaou stain detected lesions in 62 cases (3.06%), including 1 atypical glandular cell of undetermined significance (AGUS), 34 atypical squamous cells of undetermined significance (ASCUS) (1.73% of atypias), 20 (0.99%) low grade squamous intraepithelial lesions (LSIL), and 7 (0.35%) high grade squamous intraepithelial lesions (HSIL). ThinPrep detected lesions in 63 cases (3.11%), including 26 (1.28%) ASCUS, 27 (1.33%) LSIL and 10 (0.49%) HSIL. Despite this overall similarity, only 35 had a coincident cytopathologic result by both methods. The kappa concordance index between ThinPrep and Pap was 0.546. Sensitivity and specificity were 74.6 and 45.0 in ThinPrep and 69.5 and 25.0 in Papanicolaou-stained smears. High risk HPV (HR-HP 17) was positive in 13 of ZOASCUS and in 21 of 22 SIL. CONCLUSION Technologies now widely available such as Thin Prep and viral detection aim to improve accuracy of screening.
Space Improvements and Equivalences in a Functional Core Language

We explore space improvements in LRP, a polymorphically typed call-by-need functional core language. A relaxed space measure is chosen for the maximal size usage during an evaluation. It abstracts from the details of the implementation via abstract machines, but it takes garbage collection into account and thus can be seen as a realistic approximation of space usage. The results are: a context lemma for space improving translations and for space equivalences, all but one reduction rule of the calculus are shown to be space improvements, and for the exceptional one we show bounds on the space increase. Several further program transformations are shown to be space improvements or space equivalences in particular the translation into machine expressions is a space equivalence. We also classify certain space-worsening transformations as space-leaks or as space-safe. These results are a step forward in making predictions about the change in runtime space behavior of optimizing transformations in call-by-need functional languages.
Cognitive performance following spontaneous subarachnoid haemorrhage versus other forms of intracranial haemorrhage

Abstract Objective. The exact cause of cognitive deficits following intracranial haemorrhage is unclear. This prospective study examines the abilities after spontaneous subarachnoid haemorrhage (SAH), intracerebral haemorrhage (ICH) and chronic subdural haematoma (SDH) to elucidate the cognitive outcome. Patients and methods. Ninety-nine patients with SAH (N = 60), ICH (N = 25), and SDH (N = 14) were followed up for an average of 6 and 12 months post-haemorrhage. Cognitive tests were used to examine attention, memory, concentration, and executive function. Following were used for analysis: 1. the percentage of patients falling below the 25th percentile per test, 2. the general development from the first to second test point and 3. the incidence of significant changes between the test points. Significance was established as p ≤ 0.05. Results. All three types of haemorrhage resulted in deficits as concerns abstract language (53%–75%). The processing speed was below the normal levels in more than 70% of the patients tested. The cognitive performance of SAH patients was similar to that of patients with SDH and ICH patients after 6 months. The number of patients with outcomes falling below the 25th percentile (to some extent more than 75% in patients post-SAH) is high in all patient groups and mostly decreases over the course. Nevertheless, patients with SAH reveal improvements in many more areas than with ICH and SDH (p ≤ 0.006). Conclusions. The cognitive impairments following SAH, ICH and SDH deficits appear to develop in a similar way regardless of the type of haemorrhage. Cognitive improvement is most pronounced in patients with SAH.
Glutamatergic Transmission to Hypothalamic Kisspeptin Neurons Is Differentially Regulated by Estradiol through Estrogen Receptor α in Adult Female Mice

Estradiol feedback regulates gonadotropin-releasing hormone (GnRH) neurons and subsequent luteinizing hormone (LH) release. Estradiol acts via estrogen receptor α (ERα)-expressing afferents of GnRH neurons, including kisspeptin neurons in the anteroventral periventricular (AVPV) and arcuate nuclei, providing homeostatic feedback on episodic GnRH/LH release as well as positive feedback to control ovulation. Ionotropic glutamate receptors are important for estradiol feedback, but it is not known where they fit in the circuitry. Estradiol-negative feedback decreased glutamatergic transmission to AVPV and increased it to arcuate kisspeptin neurons; positive feedback had the opposite effect. Deletion of ERα in kisspeptin cells decreased glutamate transmission to AVPV neurons and markedly increased it to arcuate kisspeptin neurons, which also exhibited increased spontaneous firing rate. KERKO mice had increased LH pulse frequency, indicating loss of negative feedback. These observations indicate that ERα in kisspeptin cells is required for appropriate differential regulation of these neurons and neuroendocrine output by estradiol. SIGNIFICANCE STATEMENT The brain regulates fertility through gonadotropin-releasing hormone (GnRH) neurons. Ovarian estradiol regulates the pattern of GnRH (negative feedback) and initiates a surge of release that triggers ovulation (positive feedback). GnRH neurons do not express the estrogen receptor needed for feedback (estrogen receptor α [ERα]); kisspeptin neurons in the arcuate and anteroventral periventricular nuclei are postulated to mediate negative and positive feedback, respectively. Here we extend the network through which feedback is mediated by demonstrating that glutamatergic transmission to these kisspeptin populations is differentially regulated during the reproductive cycle and by estradiol. Electrophysiological and in vivo hormone profile experiments on kisspeptin-specific ERα knock-out mice demonstrate that ERα in kisspeptin cells is required for appropriate differential regulation of these neurons and for neuroendocrine output.
Clinical utility of endoscopic ultrasound-guided fine needle aspiration.

OBJECTIVE To assess our institution's initial experience with the clinical utility of endoscopic ultrasound (EUS)-guided fine needle aspiration. STUDY DESIGN Prospective analysis of the clinical utility of EUS-guided FNA. RESULTS Fifty-three patients underwent EUS-guided FNA of 64 sites, 28 for pancreatic masses, 15 for lymph nodes, 10 for solid lesions, 7 for cystic masses, 2 for submucosal masses and 2 for perigastrointestinal fluid. A cytopathologist was present during all procedures. An average of four passes (range, one to nine) was required to make a diagnosis in the 22 patients with pancreatic malignancies. There was one possible complication among the 53 patients. In 36 of the 53 patients, the combination of diagnostic EUS findings and cytologic diagnosis made a major change in the patient's management. CONCLUSION Because of its ability to affect patient management, EUS-guided FNA will become a more commonly used procedure, especially at oncologic centers. Since the number of fine needle passes needed for diagnosis is quite variable, it is important to have a cytopathologist participate in these procedures.
Revealing Electronic, Structural and Magnetic Phases in NdFeAsO with Electron Energy-Loss Spectroscopy

The new iron-based family of high-Tc superconductors has generated interest in the scientific community because these materials present hybrid properties from both classical BCS and highTc superconductors [1]. Iron pnictides, quaternary compounds of the form (ReFeAsO, Re=rareearth elements), present structural and magnetic phase transitions in the temperature range between 120 K to 150 K. Here, we report momentum transfer-dependent and temperaturedependent electron energy-loss spectroscopy (EELS) studies of the parent compound NdFeAsO using (scanning) transmission electron microscopy and density functional theory.
Is single room hospital accommodation associated with differences in healthcare-associated infection, falls, pressure ulcers or medication errors? A natural experiment with non-equivalent controls

Objectives A wide range of patient benefits have been attributed to single room hospital accommodation including a reduction in adverse patient safety events. However, studies have been limited to the US with limited evidence from elsewhere. The aim of this study was to assess the impact on safety outcomes of the move to a newly built all single room acute hospital. Methods A natural experiment investigating the move to 100% single room accommodation in acute assessment, surgical and older people’s wards. Move to 100% single room accommodation compared to ‘steady state’ and ‘new build’ control hospitals. Falls, pressure ulcer, medication error, meticillin-resistant Staphylococcus aureus and Clostridium difficile rates from routine data sources were measured over 36 months. Results Five of 15 time series in the wards that moved to single room accommodation revealed changes that coincided with the move to the new all single room hospital: specifically, increased fall, pressure ulcer and Clostridium difficile rates in the older people’s ward, and temporary increases in falls and medication errors in the acute assessment unit. However, because the case mix of the older people’s ward changed, and because the increase in falls and medication errors on the acute assessment ward did not last longer than six months, no clear effect of single rooms on the safety outcomes was demonstrated. There were no changes to safety events coinciding with the move at the new build control site. Conclusion For all changes in patient safety events that coincided with the move to single rooms, we found plausible alternative explanations such as case-mix change or disruption as a result of the re-organization of services after the move. The results provide no evidence of either benefit or harm from all single room accommodation in terms of safety-related outcomes, although there may be short-term risks associated with a move to single rooms.