Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic architecture of traits associated with reproductive barriers in Silene: Coupling, sex chromosomes and variation

The evolution of reproductive barriers and their underlying genetic architecture is of central importance for the formation of new species. Reproductive barriers can be controlled either by few large‐effect loci suggesting strong selection on key traits, or by many small‐effect loci, consistent with gradual divergence or with selection on polygenic or multiple traits. Genetic coupling between reproductive barrier loci further promotes divergence, particularly divergence with ongoing gene flow. In this study, we investigated the genetic architectures of ten morphological, phenological and life history traits associated with reproductive barriers between the hybridizing sister species Silene dioica and S. latifolia; both are dioecious with XY‐sex determination. We used quantitative trait locus (QTL) mapping in two reciprocal F2 crosses. One to six QTLs per trait, including nine major QTLs (PVE > 20%), were detected on 11 of the 12 linkage groups. We found strong evidence for coupling of QTLs for uncorrelated traits and for an important role of sex chromosomes in the genetic architectures of reproductive barrier traits. Unexpectedly, QTLs detected in the two F2 crosses differed largely, despite limited phenotypic differences between them and sufficient statistical power. The widely dispersed genetic architectures of traits associated with reproductive barriers suggest gradual divergence or multifarious selection. Coupling of the underlying QTLs likely promoted divergence with gene flow in this system. The low congruence of QTLs between the two crosses further points to variable and possibly redundant genetic architectures of traits associated with reproductive barriers, with important implications for the evolutionary dynamics of divergence and speciation.
Design, Test and Fabrication of a Droplet based Microfluidic Device for Clinical Diagnostics

Despite the intensive research performed towards the development of biomicrofuidic devices, information on the design, test and microfabrication of the devices is scarcely reported. Following our previous work, this paper describes the design, microfabrication and test of an electrowetting chip to transport and manipulate biosamples, towards the development of a microfluidic device for cancer diagnostics. As a first approach, experiments are performed to infer on the basic chip dimensions and configuration (size and positioning of the electrodes), allowing its best performance, evaluated based on droplet dynamics (spreading/receding diameter and contact line velocity). Then, to scale down this section, for its proper integration in the device, these basic dimensions are introduced as first guess values in a numerical model, used to optimize the distance between the electrodes, the thickness of the dielectric and the electric potential and frequency to be applied.
Investigation and comparison of the binding between tolvaptan and pepsin and trypsin: Multi‐spectroscopic approaches and molecular docking

Tolvaptan (TF), a selective arginine vasopressin V2 receptor antagonist, was approved by the Food and Drug Administration in 2009. This study mainly investigated the differences between the binding of TF with pepsin and trypsin by using a series of spectroscopy and molecular modeling methods. Thermodynamic parameters and molecular docking results suggested that the binding of TF to pepsin and trypsin were both spontaneous but driven by different forces. For pepsin, the binding was driven by hydrogen bonds and van der Waals forces; but for trypsin, it was driven by electrostatic forces and hydrophobic forces. The quenching mechanism between TF and pepsin and trypsin was investigated by fluorescence experiments and time‐resolved fluorescence spectroscopy. Synchronous fluorescence and 3‐dimensional fluorescence were used to investigate the micro‐environmental and conformational changes of pepsin and trypsin after the insertion of TF. In addition, activity‐measurement results showed that both the pepsin and trypsin activities increased with increasing TF concentration, which may help to understand the possible effect of TF on the digestion and absorption of nutrients in vivo.
Therapy development in Huntington disease: From current strategies to emerging opportunities

Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder in which patients typically present with uncontrolled involuntary movements and subsequent cognitive decline. In 1993, a CAG trinucleotide repeat expansion in the coding region of the huntingtin (HTT) gene was identified as the cause of this disorder. This extended CAG repeat results in production of HTT protein with an expanded polyglutamine tract, leading to pathogenic HTT protein conformers that are resistant to protein turnover, culminating in cellular toxicity and neurodegeneration. Research into the mechanistic basis of HD has highlighted a role for bioenergetics abnormalities stemming from mitochondrial dysfunction, and for synaptic defects, including impaired neurotransmission and excitotoxicity. Interference with transcription regulation may underlie the mitochondrial dysfunction. Current therapies for HD are directed at treating symptoms, as there are no disease‐modifying therapies. Commonly prescribed drugs for involuntary movement control include tetrabenazine, a potent and selective inhibitor of vesicular monoamine transporter 2 that depletes synaptic monoamines, and olanzapine, an atypical neuroleptic that blocks the dopamine D2 receptor. Various drugs are used to treat non‐motor features. The HD therapeutic pipeline is robust, as numerous efforts are underway to identify disease‐modifying treatments, with some small compounds and biological agents moving into clinical trials. Especially encouraging are dosage reduction strategies, including antisense oligonucleotides, and molecules directed at transcription dysregulation. Given the depth and breadth of current HD drug development efforts, there is reason to believe that disease‐modifying therapies for HD will emerge, and this achievement will have profound implications for the entire neurotherapeutics field.
Hepatitis A outbreak in Barcelona among men who have sex with men (MSM), January‐June 2017: A hospital perspective

Acute hepatitis A is transmitted mainly via the faecal‐oral route and/or contaminated aliment. Furthermore, several outbreaks in the men who have sex with men (MSM) population classified hepatitis A as a sexually transmitted disease (STD). We aimed to clarify an ongoing hepatitis A outbreak in Barcelona with respect to patients’ characteristics and viral phylogenetic analysis.
Demographic transition and factors associated with remaining in place after the 2011 Fukushima nuclear disaster and related evacuation orders

Introduction Demographic changes as a result of evacuation in the acute phase of the 2011 Fukushima nuclear disaster are not well evaluated. We estimated post-disaster demographic transitions in Minamisoma City—located 14–38 km north of the nuclear plant—in the first month of the disaster; and identified demographic factors associated with the population remaining in the affected areas. Materials and methods We extracted data from the evacuation behavior survey administered to participants in the city between July 11, 2011 and April 30, 2013. Using mathematical models, we estimated the total population in the city after the disaster according to sex, age group, and administrative divisions of the city. To investigate factors associated with the population remaining in place after the disaster, a probit regression model was employed, taking into account sex, age, pre-disaster dwelling area, and household composition. Results The overall population decline in Minamisoma City peaked 11 days after the disaster, when the population reached 7,107 people—11% of the pre-disaster level. The remaining population levels differed by area: 1.1% for mandatory evacuation zone, 12.5% for indoor sheltering zone, and 12.6% for other areas of the city. Based on multiple regression analyses, higher odds for remaining in place were observed among men (odds ratio 1.72 [95% confidence intervals 1.64–1.85]) than women; among people aged 40–64 years (1.40 [1.24–1.58]) than those aged 75 years or older; and among those living with the elderly, aged 70 years or older (1.18 [1.09–1.27]) or those living alone (1.71 [1.50–1.94]) than among those who were not. Discussion Despite the evacuation order, some residents of mandatory evacuation zones remained in place, signaling the need for preparation to respond to their post-disaster needs. Indoor sheltering instructions may have accelerated voluntary evacuation, and this demonstrates the need for preventing potentially disorganized evacuation in future nuclear events.
Cosaliency Detection Based on Intrasaliency Prior Transfer and Deep Intersaliency Mining

As an interesting and emerging topic, cosaliency detection aims at simultaneously extracting common salient objects in multiple related images. It differs from the conventional saliency detection paradigm in which saliency detection for each image is determined one by one independently without taking advantage of the homogeneity in the data pool of multiple related images. In this paper, we propose a novel cosaliency detection approach using deep learning models. Two new concepts, called intrasaliency prior transfer and deep intersaliency mining, are introduced and explored in the proposed work. For the intrasaliency prior transfer, we build a stacked denoising autoencoder (SDAE) to learn the saliency prior knowledge from auxiliary annotated data sets and then transfer the learned knowledge to estimate the intrasaliency for each image in cosaliency data sets. For the deep intersaliency mining, we formulate it by using the deep reconstruction residual obtained in the highest hidden layer of a self-trained SDAE. The obtained deep intersaliency can extract more intrinsic and general hidden patterns to discover the homogeneity of cosalient objects in terms of some higher level concepts. Finally, the cosaliency maps are generated by weighted integration of the proposed intrasaliency prior, deep intersaliency, and traditional shallow intersaliency. Comprehensive experiments over diverse publicly available benchmark data sets demonstrate consistent performance gains of the proposed method over the state-of-the-art cosaliency detection methods.
Development and feasibility of the Help to Overcome Problems Effectively (HOPE) self-management intervention for people living with multiple sclerosis

Abstract Purpose: To describe the development and feasibility of a self-management intervention called the Help to Overcome Problems Effectively (HOPE: MS), aimed at improving the physical and psychological wellbeing of people living with Multiple Sclerosis (MS). Method: HOPE: MS is an innovative, 6-week group-based, manualised self-management intervention combining positive psychology theory and practice, and cognitive behavioural therapy (CBT). Participants (N = 21) recruited via a local East Midlands branch of the MS Society attended one of three HOPE: MS interventions and completed self-reported outcome measures in week 1 and week 6. The following outcome measures were used: The Multiple Sclerosis Impact Scale; Multiple Sclerosis Fatigue Severity Scale; The Multiple Sclerosis Self-Efficacy Scale; The Adult State Hope Scale; The Hospital Anxiety and Depression Scale; The Positive and Negative Affect Scale. Results: Post-intervention (6 weeks) mean scores decreased in the physical impact (baseline M = 65.6, SD = 17.4; 6 weeks M = 55.1, SD = 17.9, 95% CI [−4.39, −16.47] and the psychological impact of MS (baseline M = 24.0, SD = 7.3; 6 weeks M = 18.9; SD = 6.3, 95% CI [−2.54, −7.66]). There was also a decrease mean fatigue severity scores (baseline 49.4, SD = 13.3, 6 weeks M = 41.1, SD = 14.4, 95% CI [−2.65, −13.44]). There was a mean decrease in depression scores (baseline M = 6.9, SD = 3.5; 6 weeks M = 4.2, SD = 2.8, 95% CI [−1.43, −4.00]). There were smaller mean decreases in anxiety (baseline M = 7.6, SD = 3.4; 6 weeks M = 6.7 (4.0), 95% CI [0.69, −2.50]) and negative affect (baseline M = 22.9, SD = 6.8; 6 weeks M = 20.8 (8.1), 95% CI [0.69, −2.50]) refer Table 3). Mean MS self-efficacy scores (baseline 21.7, SD = 4.2; 6 weeks M = 24.1, SD = 4.7, 95% CI [0.23, 4.53]), mean total hope scores (baseline M = 23.3, SD = 10.7; 6 weeks M = 32.2 (10.6), 95% CI [4.91, 12.9]), hope agency scores (baseline M = 10.5, SD = 5.7; 6 weeks M = 15.7 (6.2), 95% CI [2.37, 8.01]), hope pathways (baseline M = 12.9, SD = 6.0; 6 weeks M = 16.6 (4.9), 95% CI [2.00, 5.43]) and positive affect scores increased (baseline M = 27.3, SD = 7.1; 6 months M = 32.2, SD = 8.4, 95% CI [0.42, 9.39]). Participants positively rated the intervention quality and delivery. Conclusions: This feasibility study showed that the HOPE: MS was acceptable and useful to people living with MS. Further robust evaluations using a randomised controlled trial design with longer follow ups are needed to confirm early promising results of the HOPE: MS. Implications for rehabilitation Living with MS requires constant adjustments to cope with unpredictable symptoms. Self-management interventions have the potential to help people living with MS to improve their quality of life. A feasibility study of the HOPE: MS self-management group-based intervention showed that it was acceptable and useful to people living with MS.
Evaluating effectiveness in adolescent mental health inpatient units: A systematic review

Adolescent mental health research is a developing area. Inpatient units are the most widely used acute element of adolescent mental health services internationally. Little is known about inpatient units, particularly when it comes to measuring improvement for adolescents. Clinical outcome measurement in the broad context has gathered momentum in recent years, driven by the need to assess services. The measurement of outcomes for adolescents who access inpatient care is critical, as they are particularly vulnerable and are often considered the most difficult to treat. Following the PRISMA guidelines, the aim of this review was to assess whether adolescent inpatient units are effective and understand how outcomes are measured. CINAHL, MEDLINE with Full Text, ERIC, PsycINFO, and Cochrane databases were systematically searched. Studies were included if the inpatient units were generic and adolescents were between the mean age of 12-25 years. Furthermore, studies published in English within the last ten years were included. Exclusions were outpatient and disorder-specific inpatient settings. A total of 16 studies were identified. Each study demonstrated effectiveness on at least one outcome measure in terms of symptom stabilization. However, several outcome measures were used and therefore inpatient units lack consistency in how they measure improvement. Inpatient units are effective for the majority of young people as they result in symptom stabilization. Whilst symptom stabilization can be achieved, future research examining the mechanism of change is needed.
Selection of food combinations to optimize survival, growth, and reproduction of the amphipod Hyalella azteca in static‐renewal, water‐only laboratory exposures

Although standardized sediment toxicity testing methods have been developed for the amphipod Hyalella azteca, no standardized chronic water‐only toxicity testing methods have been established. Furthermore, optimal feeding and water quality conditions for culturing and toxicity testing with this species remained unclear. The objective of the present study was to determine the food or combination of foods that best promotes survival, growth, and reproduction of the US Lab strain of Hyalella azteca under 42‐d, water‐only, static‐renewal testing conditions. The authors conducted 7 42‐d control (no toxicant) tests with various combinations of food (including Tetramin, yeast–cereal leaves–trout chow, diatoms, wheatgrass, alfalfa, and maple leaves) and substrate types (clean “unconditioned” Nitex screens vs “conditioned” Nitex screens that were colonized by live biofilms). Over all treatments, survival ranged from 18% to 96%, dry weight per individual from 0.084 mg to 1.101 mg, and reproduction from 0 young/female to 28.4 young/female. Treatments that included Tetramin tended to result in better performance than those that did not. In particular, treatments that included Tetramin and either conditioned screens or diatoms consistently had high survival, weight, and reproduction values as well as low variability among replicates (measured as coefficient of variation). A ramped Tetramin plus diatom suspension feeding regime appears to have the greatest potential to produce consistently good performance across laboratories using static‐renewal systems. Environ Toxicol Chem 2016;35:2407–2415. © 2016 SETAC
Effect of Socio-Economic Status on the Prevalence of Diabetes

Purpose As Korean society has become industrialized and westernized, the prevalence of diabetes has increased rapidly. Environmental factors, especially socio-economic status (SES), may account for the increased prevalence of diabetes. We evaluated the associations between the prevalence of diabetes and SES as reflected by household income and education level. Materials and Methods This study was based on data obtained from the fifth Korea National Health and Nutrition Examination Survey, conducted in 2010-2012. Diabetes referred to a fasting plasma glucose ≥126 mg/dL in the absence of known diabetes, previous diagnosis of diabetes made by a physician, and/or current use of oral hypoglycemic agents or insulin. Results Household income and education level were inversely associated with the prevalence of diabetes among individuals aged 30 years or older. These associations were more prominent in females aged 30-64 years. According to household income, the odds ratio (OR) [95% confidence interval (CI)] for the lowest quartile group versus the highest quartile group was 4.96 (2.87-8.58). According to education level, the OR (95% CI) for the lowest quartile group versus the highest quartile group was 8.02 (4.47-14.4). Conclusion Public policies for the prevention and management of diabetes should be targeted toward people of lower SES, especially middle-aged females.
Aging Is Not Associated with Proteasome Impairment in UPS Reporter Mice

Background Covalent linkage of ubiquitin regulates the function and, ultimately, the degradation of many proteins by the ubiquitin-proteasome system (UPS). Given its essential role in protein regulation, even slight perturbations in UPS activity can substantially impair cellular function. Methodology/Principal Findings We have generated and characterized a novel transgenic mouse model which expresses a previously described reporter for UPS function. This UPS reporter contains a degron sequence attached to the C-terminus of green fluorescent protein, and is predominantly expressed in neurons throughout the brain of our transgenic model. We then demonstrated that this reporter system is sensitive to UPS inhibition in vivo. Conclusions/Significance Given the obstacles associated with evaluating proteasomal function in the brain, our mouse model uniquely provides the capability to monitor UPS function in real time in individual neurons of a complex organism. Our novel mouse model now provides a useful resource with which to evaluate the impact of aging, as well as various genetic and/or pharmacological modifiers of neurodegenerative disease(s).
Impaired sperm function in infertile men relies on the membrane sterol pattern

Membrane cholesterol removal appears a key step for the gain of fertility potential during sperm maturation. However, the membrane sterol pattern in sperm cells from infertile patients, with impaired sperm parameters, has been poorly investigated. To elucidate a causative link between sperm membrane composition in male fertility, here we have investigated the levels of cholesterol and its oxidized derivatives 7β‐hydroxycholesterol and 7‐keto‐cholesterol in sixteen infertile patients with oligo‐asthenozoospermia and 16 normozoospermic (N) fertile subjects. Furthermore, ten of 16 N fertile subjects agreed to receive a defined testicular thermal challenge by adhering to a programme of sauna sessions for 1 month. Semen samples were obtained from each of the participants, and sperm parameters were assessed according to the World Health Organization criteria. Sperm levels of cholesterol, 7β‐hydroxycholesterol and 7‐keto‐cholesterol were quantified by ultra‐pressure liquid chromatography mass spectrometry. The results showed that oligo‐asthenozoospermia patients had a huge amount of cholesterol content compared with fertile subjects (12.40 ± 6.05 μg/106 cells vs. 0.45 ± 0.28 μg/106 cells, p < 0.001, N and oligo‐asthenozoospermia, respectively). Also, oxidized derivatives were significantly higher in oligo‐asthenozoospermia patients (7β‐hydroxycholesterol: 1.96 ± 1.03 ng/106 cells vs. 0.075 ± 0.05 ng/106 cells, p < 0.001 and 7‐keto‐cholesterol: 1.11 ± 0.72 ng/106 cells vs. 0.005 ± 0.003 ng/106 cells, p < 0.001). Moreover, sauna exposure, in parallel with a progressive worsening of sperm motility parameters, was associated with a reversible increase in sperm cholesterol after the third and fourth week of treatment, whilst 7β‐hydroxycholesterol and 7‐keto‐cholesterol levels showed an earlier enhancement starting from the second week. Our data show for the first time in humans a strong difference in the cholesterol and its oxidized derivatives of infertile and fertile subjects. These findings suggest a strict biochemical link relating testis function, sperm membrane status and male fertility potential.
Computational study of solution behavior of magainin 2 monomers

Antimicrobial peptides (AMPs) play crucial role as mediators of the primary host defense against microbial invasion. They are considered a promising alternative to antibiotics for multidrug resistant bacterial strains. For complete understanding of the antimicrobial defense mechanism, a detailed knowledge of the dynamics of peptide-membrane interactions, including atomistic studies on AMPs geometry and both peptide and membrane structural changes during the whole process is a prerequisite. We aim at clarifying the conformation dynamics of small linear AMPs in solution as a first step of in silico protocol for establishing a correspondence between certain amino-acid sequence motifs, secondary-structure elements, conformational dynamics in solution and the intensity and mode of interaction with the bacterial membrane. To this end, we use molecular dynamics simulations augmented by well-tempered metadynamics to study the free-energy landscape of two AMPs with close primary structure and different antibacterial activity – the native magainin 2 (MG2) and an analog (MG2m, with substitutions F5Y and F16W) in aqueous solution. We observe that upon solvation, the initial α-helical structures change differently. The native form remains structured, with three shorter α-helical motifs, connected by random coils, while the synthetic analog tends predominantly to a disordered conformation. Our results indicate the importance of the side-chains at positions 5 and 16 for maintaining the solvated peptide conformation. They also provide a modeling background for recent experimental observations, relating the higher α-helical content in solution (peptide pre-folding) in the case of small linear AMPs to a lower antibacterial activity.