Miracle-dz/UniFAR-FTUs huggingface dataset:
Insights into the molecular basis for substrate binding and specificity of the wild-type L-arginine/agmatine antiporter AdiC

Significance Disease-causing bacteria are able to survive the strongly acidic environment of the stomach by activating extreme acid-resistance responses. One of these responses in gut bacteria consists of converting l-arginine into agmatine, which results in removal of one proton from the cytoplasm. In Escherichia coli, the transport protein AdiC assures the efflux of agmatine in exchange with l-arginine. We have solved the structures of wild-type AdiC in the presence and absence of the substrate agmatine at high resolution, allowing for the identification of crucial water molecules and of their functional roles in the substrate-binding pocket. Furthermore, structure-based site-directed mutagenesis combined with a radioligand binding assay improved our understanding of substrate binding and specificity of the l-arginine/agmatine antiporter AdiC. Pathogenic enterobacteria need to survive the extreme acidity of the stomach to successfully colonize the human gut. Enteric bacteria circumvent the gastric acid barrier by activating extreme acid-resistance responses, such as the arginine-dependent acid resistance system. In this response, l-arginine is decarboxylated to agmatine, thereby consuming one proton from the cytoplasm. In Escherichia coli, the l-arginine/agmatine antiporter AdiC facilitates the export of agmatine in exchange of l-arginine, thus providing substrates for further removal of protons from the cytoplasm and balancing the intracellular pH. We have solved the crystal structures of wild-type AdiC in the presence and absence of the substrate agmatine at 2.6-Å and 2.2-Å resolution, respectively. The high-resolution structures made possible the identification of crucial water molecules in the substrate-binding sites, unveiling their functional roles for agmatine release and structure stabilization, which was further corroborated by molecular dynamics simulations. Structural analysis combined with site-directed mutagenesis and the scintillation proximity radioligand binding assay improved our understanding of substrate binding and specificity of the wild-type l-arginine/agmatine antiporter AdiC. Finally, we present a potential mechanism for conformational changes of the AdiC transport cycle involved in the release of agmatine into the periplasmic space of E. coli.
Acute stress enhances heterodimerization and binding of corticosteroid receptors at glucocorticoid target genes in the hippocampus

Significance Glucocorticoid hormones are important mediators of the stress response and implicated in the etiology of stress-related psychiatric disorders. Glucocorticoids act via mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in the hippocampus, resulting in altered transcription of target genes. Currently, however, little information is available about how they interact with the genome after stress in vivo. Here, we show that an acute stressful challenge results in an increased interaction of both MRs and GRs with their genomic recognition sites. Moreover, they may interact with these sites not just as homodimers but also, as heterodimers, the extent of which is highly gene-dependent. These findings provide insight into how MRs and GRs interact with the hippocampal genome after stress in vivo. A stressful event results in secretion of glucocorticoid hormones, which bind to mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in the hippocampus to regulate cognitive and affective responses to the challenge. MRs are already highly occupied by low glucocorticoid levels under baseline conditions, whereas GRs only become substantially occupied by stress- or circadian-driven glucocorticoid levels. Currently, however, the binding of MRs and GRs to glucocorticoid-responsive elements (GREs) within hippocampal glucocorticoid target genes under such physiological conditions in vivo is unknown. We found that forced swim (FS) stress evoked increased hippocampal RNA expression levels of the glucocorticoid-responsive genes FK506-binding protein 5 (Fkbp5), Period 1 (Per1), and serum- and glucocorticoid-inducible kinase 1 (Sgk1). Chromatin immunoprecipitation (ChIP) analysis showed that this stressor caused substantial gene-dependent increases in GR binding and surprisingly, also MR binding to GREs within these genes. Different acute challenges, including novelty, restraint, and FS stress, produced distinct glucocorticoid responses but resulted in largely similar MR and GR binding to GREs. Sequential and tandem ChIP analyses showed that, after FS stress, MRs and GRs bind concomitantly to the same GRE sites within Fkbp5 and Per1 but not Sgk1. Thus, after stress, MRs and GRs seem to bind to GREs as homo- and/or heterodimers in a gene-dependent manner. MR binding to GREs at baseline seems to be restricted, whereas after stress, GR binding may facilitate cobinding of MR. This study reveals that the interaction of MRs and GRs with GREs within the genome constitutes an additional level of complexity in hippocampal glucocorticoid action beyond expectancies based on ligand–receptor interactions.
Public Attitudes to Economic Inequality

Economic inequality in the UK stands at historically high levels and there is emerging evidence that a high level of inequality may cause socio-economic problems. However, little is known about public attitudes on this issue. The study: - starts by examining public attitudes to inequality and poverty; - considers public attitudes to redistribution; - highlights apparent contradictions in public attitudes; - explores the more underlying values people draw on when forming their opinions on these issues; - reviews key findings, and discusses policy implications and research gaps
Pulmonary Arterial Contractility in Neonatal Lambs Increases with 100% Oxygen Resuscitation

The optimal Fio2 during neonatal resuscitation is a subject of controversy. The effect of exposure to high levels of inspired oxygen on pulmonary arterial (PA) contractility is not known. We studied differences in PA vasoreactivity in term lambs initially ventilated with 21% or 100% oxygen, followed by continued ventilation using oxygen as needed for 24 h, or ventilated with 100% oxygen for 24 h and room air breathing 1-d-old lambs. Term lambs were delivered by cesarean section, intubated, and ventilated with 21% (21%Res) or 100% oxygen (100%Res) for the first 30 min of life. Subsequently, the ventilator Fio2 was adjusted to maintain a Pao2 between 45 and 65 mm Hg for 24 h. Five lambs were ventilated continuously with 100% oxygen (100%24h). Six spontaneously breathing newborn lambs (RA Spont) were studied for comparison. Lambs were killed at 24 h of life and PA rings were isolated and contracted with norepinephrine (NE) and KCl and some were relaxed with A23187 and SNAP in tissue baths. NE and KCl induced contractions were highest in PA isolated from 100%24h lambs, and were significantly higher in 100%Res lambs than PA from 21%Res lambs. Contraction responses in PA from RA Spont lambs were similar to 21%Res lambs. Relaxations to A23187 and SNAP were similar among all ventilated groups. PA contractility to NE and KCl is increased following both brief (30 min) and prolonged (24 h) exposure to 100% oxygen during mechanical ventilation. In contrast, normoxic resuscitation and ventilation do not increase PA contractility.
Millennial Student Preference of Audience Response System Technology

Previous research studies have found that audience response systems or “clickers” provide significant classroom, learning, and assessment benefits in higher education. However, there are few to no research studies that have pitted popular clicker systems against each other using data collected from a sample of millennial students in public health–related professions. As a result, the purpose of this study was to compare two popular audience response systems in the college classroom with undergraduate students, specifically those studying public health. The study was implemented using a mixed methods quasi-experimental crossover design with three observation points over one academic year. Both qualitative and quantitative data were collected. Findings suggest that undergraduate students prefer using a dedicated “clicker” system to respond to questions from an audience response system than a system that requires them to use their personal cell phones.
Urban Middle-Class Buddhist Reform Movements in Thailand: Economic Systems and Business Ethics

Economic justice is a critical concern for many societies, frequently fostering debate on the nature of economic systems. Often religious revival contributes substantially to this discussion, because religion is a major source of ethics. This paper examines ‘Buddhist economics’ in modern urban reform Buddhism in Thailand. The three movements discussed here all seek high ethical standards, and stress ethical responsibility, but differ substantially in how much they feel behavior is conditioned by context, and thus, in how much the system needs to change to achieve a more moral society.
llogeneic hematopoietic cell transplantation for adult patients with reatment-related acute myeloid leukemia during first remission : omparable to de novo acute myeloid leukemia

Therapy-related acute myeloid leukemia (T-AML) is associated with poor prognosis after conventional therapy. Allogeneic hematopoietic cell transplantation (allo-HCT) has been proposed as a treatment for T-AML; however, data comparing outcomes of transplants for patients with de novo AML and T-AML are limited. Sixteen adult patients with T-AML during first complete remission after malignant disease received allo-HCT at the Peking University Institute of Hematology between January 1, 2006 and December 31, 2014. Eighty patients with de novo AML were selected using the case-pair method. The 3-year overall survival and leukemia-free survival for T-AML versus de novo AML patients were 66% vs. llogeneic hematopoietic cell ransplantation herapy-related 79% (P = 0.14) and 64% vs. 77% (P = 0.13), respectively. The 3-year cumulative non-relapse mortality rates for T-AML versus de novo AML patients were 13% vs. 9% (P = 0.47), respectively; the relapse rates were 20% vs. 13% (P = 0.25), respectively. Our results suggest that the prognosis of T-AML is comparable to that of de novo AML after transplantation. Although T-AML shows poorer prognosis than de novo AML after conventional therapies, allo-HCT can markedly improve the prognosis of T-AML. © 2016 Published by Elsevier Ltd.
Collagen scaffold combined with human umbilical cord‐derived mesenchymal stem cells promote functional recovery after scar resection in rats with chronic spinal cord injury

Effective therapeutic strategies for treating chronic spinal cord injury (SCI) are currently unavailable. Scar tissue in the lesion area is a main inhibitory factor for axonal regeneration and repair of chronic SCI. In this study, scar tissue was surgically resected from adult rats with 12 week chronic SCI and then collagen scaffold (NeuroRegen Scaffold; NRS) and human umbilical cord‐derived mesenchymal stem cells (hUC‐MSCs) were implanted into the resected cavity to repair chronic SCI. The results demonstrated that the locomotor function of rats was not affected by surgical scar resection, indicating its safety in treating chronic SCI. Implanting NRS and hUC‐MSCs promoted locomotion in rats and improved cortical motor‐ and somatosensory‐evoked potentials. Furthermore, implanting NRS and hUC‐MSCs promoted neurofilament‐ and β‐tubulin‐III‐positive neural regeneration and remyelination, elicited β‐tubulin‐III‐positive neuron production in the lesion area and blocked astrocyte growth outside the lesion area. In conclusion, implanting NRS in combination with hUC‐MSCs provided a beneficial microenvironment for neural regeneration, showing significant therapeutic effects for chronic SCI.
Disease induced dynamics in host–parasitoid systems: chaos and coexistence

All animals and plants are, to some extent, susceptible to disease caused by varying combinations of parasites, viruses and bacteria. In this paper, we present a mathematical model of interactions between a host, two parasitoids and a pathogen which shows that the presence of an infection can preserve and promote diversity in such multi-species systems. Initially, we use a system of ordinary differential equations to investigate interactions between two species of parasitoids, a host and a host infection. We show that the presence of all four species is necessary for the system as a whole to persist, and that in particular, the presence of the pathogen is necessary for the coexistence of the two parasitoid species. The inclusion of infection induces a wide range of dynamics, including chaos, and these dynamics are robust for a wide range of parameter values. We then extend the model to include spatial effects by introducing random motility (diffusion) of all three species and examine the subsequent spatio-temporal dynamics, including travelling waves and other more complicated heterogeneous behaviour. The computational simulation results of the model suggest that infection in the hosts can blunt the effects of competition between parasitoids, allowing the weaker competitor to survive. Regardless of the nature of the stability of the coexistent steady state of the system, there is an initial period of transient dynamics, the length of which can be extended by an appropriate choice of initial conditions. The existence of these transient dynamics suggests that systems subject to regular restoration to a starting state, such as agro-ecosystems, may be kept in a continual state of dynamic transience, and this has implications for the use of natural enemies to control insect pests, the preservation of biodiversity in farmland habitats and the more general dynamics of disease processes.
Recovery of Swallowing Disorders in Patients Undergoing Supracricoid Laryngectomy with Botulinum Toxin Therapy

In recent decades, functional laryngeal surgery has become a widespread method of treating glottic and supraglottic neoplasms, since it ensures an oncological outcome comparable to that of radical surgery and functional results that are conducive to a good quality of life. The most common postoperative complaints for this type of surgery are swallowing disorders, which can thwart good surgical results, especially when severe. Five supracricoid laryngectomees with swallowing disorders unresolved by speech therapy were treated by percutaneous injection of botulinum toxin under electromyographic control. All patients presented marked improvement in their complaints. A single session of botulinum toxin type A treatment resolved the dysphagia in all cases.
Lamina cribrosa configuration in tilted optic discs with different tilt axes: a new hypothesis regarding optic disc tilt and torsion.

PURPOSE To determine the configuration of the anterior lamina cribrosa (LC) surface in eyes with different tilt axes. METHODS A total of 114 eyes (66 glaucomatous eyes and 48 healthy eyes) with tilted optic discs (ovality index > 1.3) were divided into vertical- and horizontal-tilt groups according to their optic disc tilt axis. Serial horizontal B-scan images of the ONH were obtained from each eye using enhanced-depth imaging spectral-domain optical coherence tomography. After three-dimensional reconstruction of the images, the anterior LC surface depth (LCD) was measured in each of the oblique scans containing the long disc axis and in the seven horizontal B-scans that divided the anterior LC surface vertically into eight parts. RESULTS The configuration of the anterior LC surface along the long disc axis differed markedly between groups. The vertical-tilt group had a larger LCD at superior locations than at inferior locations, while the pattern was the opposite in the horizontal-tilt group. The RNFL thinning in glaucomatous eyes was most prominent at both the superotemporal and inferotemporal sectors in the vertical-tilt group, while it was predominated at the inferotemporal sector in the horizontal-tilt group. CONCLUSIONS The configuration of the anterior LC surface in eyes with differed optic disc tilt axis suggested that the horizontally-tilted optic discs may not be resulted from the optic disc rotation, but from the optic disc tilt centered on the oblique axis. The preferential location of RNFL thinning could be explained by the LCD profile differing according to the tilt axis.
Parental Symptoms of Posttraumatic Stress After Pediatric Extracorporeal Membrane Oxygenation*

Objective: To investigate the prevalence of posttraumatic stress symptoms in parents of children who have been supported on extracorporeal membrane oxygenation and to explore associated factors. Design: Descriptive cross-sectional study. Setting: A specialist pediatric tertiary center in the United Kingdom. Subjects: Parents (n = 52) of children who had been supported with extracorporeal membrane oxygenation at least 6 months previously. Interventions: None. Measurements and Main Results: Self-reported questionnaires were completed measuring posttraumatic stress symptom, family functioning, depression, anxiety, and demographic variables. Approximately 20% of parents experienced posttraumatic stress symptoms at levels suggestive of a diagnosis of posttraumatic stress disorder, irrespective of the time that had elapsed since extracorporeal membrane oxygenation. Although having a child who had ongoing illness before extracorporeal membrane oxygenation was associated with avoidance posttraumatic stress symptoms, results suggest that other previously identified risk factors, such as gender and family functioning, may not be risk factors for posttraumatic stress symptom in this population. Conclusions: A substantial number of parents in this population experience posttraumatic stress symptom. Psychological interventions may be targeted toward those whose child has had ongoing illness before extracorporeal membrane oxygenation.
Mother–Son Discrepant Reporting on Parenting Practices: The Contribution of Temperament and Depression

Despite low to moderate convergent correlations, assessment of youth typically relies on multiple informants for information across a range of psychosocial domains including parenting practices. Although parent–youth informant discrepancies have been found to predict adverse youth outcomes, few studies have examined contributing factors to the explanation of informant disagreements on parenting practices. The current study represents the first investigation to concurrently examine the role of mother and son’s self-reported affective dimensions of temperament and depression as pathways to informant discrepancies on parenting practices. Within a community sample of 174 mother–son dyads, results suggest that whereas mother’s self-reported temperament evidenced no direct effects on discrepancies, the association between the product term of mother’s negative and positive temperament and discrepancies on positive parenting was fully mediated by mother’s depression (a mediated moderation). In contrast, son’s self-reported temperament evidenced both direct and indirect effects, partially mediated by depression, on rating discrepancies for positive parenting. All told, both son’s self-reported affective dimensions of temperament and depression contributed to the explanation of discrepant reporting on parenting practices; only mother’s self-reported depression, but not temperament, uniquely contributed. Results highlight the importance of considering both parent and youth’s report in the investigation of informant discrepancies on parenting practices.
Effects of Sulfuroxy Anions on Degradation of Pentachlorophenol by a Methanogenic Enrichment Culture

We studied the degradation of pentachlorophenol (PCP) under methanogenic and sulfate-reducing conditions with an anaerobic mixed culture derived from sewage sludge. The consortium degraded PCP via 2,3,4,5-tetrachlorophenol, 3,4,5-trichlorophenol, and 3,5-dichlorophenol and eventually accumulated 3-chlorophenol. Dechlorination of PCP and metabolites was inhibited in the presence of sulfate, thiosulfate, and sulfite. A decrease in the rate of PCP transformation was noted when the endogenous dissolved H2 was depleted below 0.11 μM in sulfate-reducing cultures. The effect on dechlorination observed with sulfate could be relieved by addition of molybdate, a competitive inhibitor of sulfate reduction. Addition of H2 reduced the inhibition observed with sulfuroxy anions. The inhibitory effect of sulfuroxy anions may be due to a competition for H2 between sulfate reduction and dechlorination. When cultured under methanogenic conditions, the consortium degraded several chlorinated and brominated phenols.
The immune response to chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is predominantly of the Th2 type

Most cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa lung infection have a persistent acute type lung inflammation dominated by polymorphonuclear neutrophils (PMN) and a pronounced antibody response against P. aeruginosa. We speculated whether this immune response in CF is of the Th2 type and whether a change to a Th1 type immune response could improve the prognosis. Therefore, we studied 14 CF patients with (CF +P) and 14 CF patients without (CF –P) chronic P. aeruginosa lung infection. The specific production of interferon‐gamma (IFN‐γ) and interleukin‐4 (IL‐4) by peripheral blood mononuclear cells was determined. Cells from CF +P patients had lower IFN‐γ (p<0.05) and higher IL‐4 (p<0.005) production as compared to cells from CF ‐P patients. Furthermore, a positive correlation between IFN‐γ production and lung function was found (FVC: Rho=0.637; p<0.03; FEV1: Rho=0.524; p<0.07). We conclude that a Th2 type immune response is most frequent in CF patients with chronic P. aeruginosa lung infection, and the patients with a Th1‐dominated immune response had the best lung function. The clinical implication is that a change to a Th1 type immune response might improve the prognosis in these patients.
Fortune or fortitude? Determinants of successful adjustment with IMF programs

Full adjustment programs in the wake of crisis episodes exact a major toll on a country’s economy, yet not all are blessed with success.We identify adjustment needs by a country’s decision to approach the IMF for official assistance.We then investigate the factors conducive to successful exit from official assistance during more than 170 adjustment episodes by means of a panel regression framework. In contrast to the existing literature, we do not use absolute benchmarks. We define success as a resumption of real GDP growth and a reduction of government debt compared to the pre-program period. Our econometric results suggest stringent policy action do play a role for the probability of success. At the same time, we also find that successful exit also very much depends on supportive external conditions and, linked to that, the degree of openness of an economy. JEL classification: E61, F33, G01, H81 Keywords: Fiscal adjustment, financial crises, IMF lending
Evaluation of colony losses in Israel in relation to the incidence of pathogens and pests

To evaluate symptoms, extent, and possible causes of colony decline and losses in Israel, we carried out (1) a survey of honeybee colony losses and potential causes via mail and phone; (2) systematic sampling of healthy and problematic beehives after requeening in the winter; (3) detection of Varroa and pathogens including, viruses and Nosema ceranae, by microbiological means and sensitive RT-PCR. From 58 beekeepers (46 000 colonies) interviewed, 40% complained of extensive colony loses during 2008. Examination and sampling for pests and pathogens of 113 hives in the winter of 2009 showed 35% of hives with Nosema and 21% with V. destructor. The most frequent viruses detected were Black Queen Cell Virus, Israeli Acute Paralysis Virus, and Deformed Wing Virus. A significant negative correlation was found between worker population in the hive and the presence of viral and Nosema infections.