Miracle-dz/UniFAR-FTUs huggingface dataset:
Illuminating the activation mechanisms and allosteric properties of metabotropic glutamate receptors

In multimeric cell-surface receptors, the conformational changes of the extracellular ligand-binding domains (ECDs) associated with receptor activation remain largely unknown. This is the case for the dimeric metabotropic glutamate receptors even though a number of ECD structures have been solved. Here, using an innovative approach based on cell-surface labeling and FRET, we demonstrate that a reorientation of the ECDs is associated with receptor and G-protein activation. Our approach helps identify partial agonists and highlights allosteric interactions between the effector and binding domains. Any approach expected to stabilize the active conformation of the effector domain increased the agonist potency in stabilizing the active ECDs conformation. These data provide key information on the structural dynamics and drug action at metabotropic glutamate receptors and validate an approach for tackling such analysis on other receptors.
The Possibility of Bacterial Meningitis in First Simple or Complex Febrile Seizures among Children 6-24 Months of Age : An Evaluation of 564 Patients

Purpose: The aim of this study was to assess the probability of bacterial meningitis presenting with a first simple febrile seizure or complex febrile seizure without any conspicuous signs of meningitis. Methods: This was a record based cross-sectional study of 564 patients of 6-24 months of age and was evaluated in a paediatric emergency department between 2007 and 2013 for their first febrile seizure. Results: In the study group 452 (80%) were diagnosed with simple febrile seizure and 112 (20%) with complex febrile seizure. In neither group was any patient diagnosed with bacterial meningitis. The number of children undergoing lumbar puncture was significantly higher in the complex febrile seizure group (p<0.001). Conclusion: The ratio of bacterial meningitis was not increased in patients with complex febrile seizure who otherwise appeared well and lacked clinical findings of meningitis like the patients with simple febrile seizure.
Particle Filter Based on Strong Tracking Filter

One of the key issues for particle filter is the proposal distribution. A new proposal distribution, the strong tracking filter (STF) proposal distribution, is presented. The time-varied fading factor in the STF that can be tuned on line makes the algorithm adaptive. In the bearings-only passive target tracking examples, the simulation results confirm the efficiency of particle filter with the new proposal distribution.
Role of Heat Stress Transcription Factor HsfA5 as Specific Repressor of HsfA4*

Unlike other eukaryotes, plants possess a complex family of heat stress transcription factors (Hsfs) with usually more than 20 members. Among them, Hsfs A4 and A5 form a group distinguished from other Hsfs by structural features of their oligomerization domains and by a number of conserved signature sequences. We show that A4 Hsfs are potent activators of heat stress gene expression, whereas A5 Hsfs act as specific repressors of HsfA4 activity. The oligomerization domain of HsfA5 alone is necessary and sufficient to exert this effect. Due to the high specificity of the oligomerization domains, other class A Hsfs are not affected. Pull-down assay and yeast two-hybrid interaction tests demonstrate that the tendency to form HsfA4/A5 heterooligomers is stronger than the formation of homooligomers. The specificity of interaction between Hsfs A4 and A5 was confirmed by bimolecular fluorescence complementation experiments. The major role of the representatives of the HsfA4/A5 group, which are not involved in the conventional heat stress response, may reside in cell type-specific functions connected with the control of cell death triggered by pathogen infection and/or reactive oxygen species.
P-antigen-recognizing fimbriae from human uropathogenic Escherichia coli strains

P-antigen-recognizing fimbriae (P fimbriae) from four pyelonephritogenic Escherichia coli strains and type 1 fimbriae from an E. coli strain and a Salmonella typhimurium strain were purified. The P fimbriae were morphologically similar to type 1 fimbriae. The purified P fimbriae agglutinated neuraminidase-treated human P1 and P2k erythrocytes but not p erythrocytes, which lack all P-blood group-specific glycosphingolipids. However, coating of neuraminidase-treated p erythrocytes with globoside rendered such erythrocytes agglutinable by the P fimbriae. The hemagglutinations were in all instances fully inhibited by the synthetic alpha-D-Galp-(1-4)-beta-D-Galp-1-O-Me glycoside. The binding specificity of the P fimbriae could also be demonstrated by using fimbriae coated onto latex particles and nontreated erythrocytes. It was thus concluded that the P fimbriae recognize and bind to the alpha-D-Galp-(1-4)-beta-D-Galp carbohydrate sequence occurring in the series of P-blood group antigen-specific glycosphingolipids. In contrast to both type 1 fimbriae, all four P fimbriae preparations showed multiple bands in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Antisera were raised in rabbits against the various E. coli fimbriae. In enzyme-linked immunosorbent assays each one of the antisera to the P fimbriae reacted to titers of log 4 to 7 with both the homologous and the heterologous P fimbriae, but not with the type 1 fimbriae of E. coli. In a reciprocal fashion, the antiserum to the type 1 fimbriae of one E. coli strain reacted only with the homologous type 1 but not with any of the P fimbriae preparations.
Antidepressant properties of aqueous macerate from Gladiolus dalenii corms.

BACKGROUND Gladiolus dalenii Van Geel (Iridaceae) has been used for the treatment of depression and psychotic disorders in African traditional medicine. The aim of this study was to assess the effect of the aqueous extract from the corm of Gladiolus dalenii and its possible mechanisms of action. MATERIALS AND METHODS We assessed the antidepressant properties of G. dalenii corm aqueous extract in mice, using the open field, forced swimming, and tail suspension tests. Spontaneous locomotor activity of mice given various doses of G. dalenii extract (per os) was determined in the open field, whereas immobility was evaluated in the other two tests. RESULTS Extract maximal effect was observed at 15 mg/kg, as mice displayed a marked reduction in immobility time in both the forced swimming test (80%) and the tail suspension test (66%). In further studies aimed at investigating the mechanism of action of G. dalenii extract, the latter significantly antagonized the effect of N-methyl-D-aspartate (NMDA, 75 mg/kg) at both the doses 15 mg/kg (p<0.001) and 150 mg/kg (p=0.004). A significant reduction in immobility time was also observed following treatment with combinations of a sub-effective dose of extract (7.5 mg/kg) with either the NMDA receptor antagonist D-(-)-2-amino-7-phosphonoheptanoic acid (D-AP7, 50 mg/kg, P< 0.001), the serotonin reuptake inhibitor fluoxetine (5 and 10 mg/kg, P< 0.001 and P< 0.001 respectively), and the multi-target antidepressant imipramine (5 and 10 mg/kg, P< 0.001 and P< 0.001 respectively). Moreover, neither G. dalenii extract alone nor its combinations with NMDA ligands imipramine and fluoxetine enhanced mouse spontaneous locomotor activity. CONCLUSION Altogether, these results suggest that G. dalenii has antidepressant properties, probably mediated through interactions with NMDA, serotonin and/ or noradrenergic systems, and may justify its use in traditional medicine.
Infectious diseases. Can new chemistry make a malaria drug plentiful and cheap?

Infectious DiseasesGerman chemist Peter Seeberger, head of a team of 70 researchers at the Max Planck Institute of Colloids and Interfaces in Potsdam, has found a way to produce artemisinin, the world's most important antimalaria medication, much more cheaply and easily than current methods allow. In January, Seeberger published a paper outlining how a technique called flow chemistry might make a key step in the drug's production chain more efficient. If the promise comes true, it could be a boon for the global fight against malaria, because the current price, between $0.80 and $1.20 per treatment course, is still a major factor hampering access to artemisinin drugs. Some scientists are impressed. But Seeberger's method has yet to prove its mettle.
Regulation of Escherichia coli hchA, a stress‐inducible gene encoding molecular chaperone Hsp31

Escherichia coli Hsp31 is a homodimeric member of the ThiI/DJ‐1/PfpI superfamily that combines molecular chaperone and aminopeptidase activities. Although it was originally identified on the basis of its induction by heat shock, little is known about the regulation of hchA, the structural gene encoding Hsp31. Here, we show that hchA is transcribed from dual promoters recognized by the σD (σ70) and σS (σ38) subunits of RNA polymerase (E). In exponentially growing cells, the nucleoid‐binding protein H‐NS downregulates Hsp31 synthesis, and hchA thermal induction primarily relies on the relief of H‐NS‐mediated silencing of EσD‐dependent transcription. This uncommon alternative to the use of a heat‐shock sigma factor guarantees that Hsp31 concentration remains high throughout the length of the high temperature exposure phase. Entry into stationary phase leads to enhanced hchA transcription from its EσS‐dependent promoter. Consistent with a role of Hsp31 in the management of starvation, hchA null mutants exhibit a decrease ability to survive in deep stationary phase relative to hchA+ cells. Based on hchA heat‐inducibility and membership in the σS general stress regulon, we propose that Hsp31 performs a protective function under a wide range of stress conditions.
A Protective Glycosylphosphatidylinositol-Anchored Membrane Protein of Plasmodium yoelii Trophozoites and Merozoites Contains Two Epidermal Growth Factor-Like Domains

ABSTRACT Using sera from mice immunized and protected againstPlasmodium yoelii malaria, we identified a novel blood-stage antigen gene, pypag-2. The 2.1-kbpypag-2 cDNA contains a single open reading frame that encodes a 409-amino-acid protein with a predicted molecular mass of 46.8 kDa. Unlike many characterized plasmodial antigens, blocks of tandemly repeated amino acids are lacking in the pypAg-2 protein sequence. Recombinant pypAg-2, comprising the full-length protein minus the predicted N-terminal signal and C-terminal anchor sequences, was produced and used to raise a high-titer polyclonal rabbit antiserum. This antiserum was used to identify and characterize the native protein through immunoblotting, immunoprecipitation and immunofluorescence assays. Consistent with the presence of a glycosylphosphatidylinositol anchor, pypAg-2 fractionated with the detergent phase of Triton X-114-solubilized proteins and could be metabolically labeled with [3H]palmitic acid. By immunofluorescence, pypAg-2 expression was localized to both the trophozoite and merozoite membranes. Similar to Plasmodium falciparum merozoite surface protein 1, pypAg-2 contains two C-terminal epidermal growth factor (EGF)-like domains. Most importantly, immunization with recombinant pypAg-2 protected mice against lethal P. yoeliimalaria. Thus, pypAg-2 is a target of protective immune responses and represents a novel addition to the family of merozoite surface proteins that contain one or more EGF-like domains.
Opportunities and challenges in the use of personal health data for health research

OBJECTIVE Understand barriers to the use of personal health data (PHD) in research from the perspective of three stakeholder groups: early adopter individuals who track data about their health, researchers who may use PHD as part of their research, and companies that market self-tracking devices, apps or services, and aggregate and manage the data that are generated. MATERIALS AND METHODS A targeted convenience sample of 465 individuals and 134 researchers completed an extensive online survey. Thirty-five hour-long semi-structured qualitative interviews were conducted with a subset of 11 individuals and 9 researchers, as well as 15 company/key informants. RESULTS Challenges to the use of PHD for research were identified in six areas: data ownership; data access for research; privacy; informed consent and ethics; research methods and data quality; and the unpredictable nature of the rapidly evolving ecosystem of devices, apps, and other services that leave "digital footprints. " Individuals reported willingness to anonymously share PHD if it would be used to advance research for the good of the public. Researchers were enthusiastic about using PHD for research, but noted barriers related to intellectual property, licensing, and the need for legal agreements with companies. Companies were interested in research but stressed that their first priority was maintaining customer relationships. CONCLUSION Although challenges exist in leveraging PHD for research, there are many opportunities for stakeholder engagement, and experimentation with these data is already taking place. These early examples foreshadow a much larger set of activities with the potential to positively transform how health research is conducted.
A New Broadband Quasi Yagi–Uda Antenna With an EBG-Truncated Ground Plane

The design of a new broadband quasi Yagi-Uda antenna is presented. The antenna is composed of an electromagnetic band-gap (EBG)-truncated ground plane and a feeding network formed by a Marchand balun and a coupling network. The quasi Yagi-antenna was designed to work at a central frequency of 3.5 GHz using a 30-mil FR4 substrate. The simulated and measured results show a relative bandwidth better than 53%, a cross polarization lower than -19 dB in the main lobe, and a front-to-back ratio better than 12 dB in the entire bandwidth.
Genome-Wide Association Study of Metabolic Syndrome in Koreans

Metabolic syndrome (METS) is a disorder of energy utilization and storage and increases the risk of developing cardiovascular disease and diabetes. To identify the genetic risk factors of METS, we carried out a genome-wide association study (GWAS) for 2,657 cases and 5,917 controls in Korean populations. As a result, we could identify 2 single nucleotide polymorphisms (SNPs) with genome-wide significance level p-values (<5 × 10-8), 8 SNPs with genome-wide suggestive p-values (5 × 10-8 ≤ p < 1 × 10-5), and 2 SNPs of more functional variants with borderline p-values (5 × 10-5 ≤ p < 1 × 10-4). On the other hand, the multiple correction criteria of conventional GWASs exclude false-positive loci, but simultaneously, they discard many true-positive loci. To reconsider the discarded true-positive loci, we attempted to include the functional variants (nonsynonymous SNPs [nsSNPs] and expression quantitative trait loci [eQTL]) among the top 5,000 SNPs based on the proportion of phenotypic variance explained by genotypic variance. In total, 159 eQTLs and 18 nsSNPs were presented in the top 5,000 SNPs. Although they should be replicated in other independent populations, 6 eQTLs and 2 nsSNP loci were located in the molecular pathways of LPL, APOA5, and CHRM2, which were the significant or suggestive loci in the METS GWAS. Conclusively, our approach using the conventional GWAS, reconsidering functional variants and pathway-based interpretation, suggests a useful method to understand the GWAS results of complex traits and can be expanded in other genomewide association studies.
Prevalence and clinical features of newly diagnosed generalized anxiety disorder patients in Spanish primary care settings: the GADAP study.

BACKGROUND Generalized anxiety disorder (GAD) is the most impairing anxiety disorder, a high percentage of patients remain undiagnosed at the primary care level. The aim of this study was to determine the clinical features of newly diagnosed GAD patients. METHOD Multicentre, cross-sectional observational study conducted in primary care settings. GAD patients were diagnosed according to the MINI psychiatric interview, and were included in the study if their score for GAD-7 was ≥10. Anxiety and depression levels, and sleep disturbances were determined by HADS and MOS-sleep scales, respectively. Data regarding pharmacological treatment and healthcare resources in the previous 3 months were collected. RESULTS 2,232 patients were recruited; average GAD-7 score was 14.1 ± 2.7 (mean symptom duration 32.3 ± 43.3 months). 96.9% of patients had a comorbid medical illness, with 83.9% patients suffering from pain. Psychiatric comorbidities were present in 66.4% of patients (social anxiety 37%, major depression 19.1%). HADS-depression scores rendered 28.4% and 55.9% of patients as probable and depressive cases, respectively. Patients' sleep rated 6.2 ± 1.9 on average in a 1 to 10 visual analogue scale. Only 34.9% of patients were following non-pharmacological treatment and 86.5%, 69.4% and 49.7% were treated with benzodiazepines, antidepressants and antiepileptics, respectively. The mean number of visits to the primary care physician in the previous 3 months was 5 times. LIMITATIONS Cross-sectional design; does not allow to infer causality.
Modelling and analysis of low-power wide-area networks

In this paper, we investigate the uplink transmission performance of low-power wide-area networks (LPWANs) with regards to coexisting radio modules using LoRa as an example. In doing so we adopt a new topology to model the network where the node locations of the network of focus (LoRa) follow a Poisson cluster process (PCP) while other coexisting interfering radio modules follow a Poisson point process (PPP). To characterize the performance of the proposed model as well as obtain insights, both analytical and closed-form approximated expressions for coverage probability are derived. Based on this, area spectrum efficiency, and energy efficiency are further characterized. These results demonstrate the degree to which the performance, with regard to the aforementioned metrics, is capable of being enhanced through varying the density of the deployment of LoRa nodes around each LoRa receiver. Moreover, simulation results unveil that an optimal value of active LoRa nodes in each cluster exists that maximizes area spectrum efficiency.
Coping strategies and anxiety in caregivers of palliative cancer patients.

The study purpose was to determine the relationship between coping strategies and anxiety in primary family caregivers of palliative cancer patients. A cross-sectional study was carried out in a Pain and Palliative Care Unit in Spain. Data were collected through interviews from fifty primary family caregivers of palliative cancer patients. Main research variables were: (1) dependent variable: anxiety (subscale of anxiety from Goldberg's scale); (2) independent variable: coping (Brief COPE); (3) control variables: functional capacity and perceived burden. Analyses comprised descriptive statistics, correlation coefficients and multiple linear regression. Anxiety was present in the majority of caregivers surveyed (76%). Anxiety was related to the perception of perceived burden (β = 0.42, P < 0.001), the emotion-focused coping (β = -0.28, P = 0.01) and dysfunctional coping (β = 0.41, P < 0.001), after adjusting for control variables. Thus, emotion-focused coping is negatively associated with anxiety, while dysfunctional coping is positively associated with anxiety. Problem-focused coping is not related to anxiety. Assessment of coping should be done in a systematic way in caregivers of palliative cancer patients.
Influence of Aggregation on Interaction of Lipophilic, Water‐Insoluble Azaphthalocyanines with DOPC Vesicles

Dioleoylphosphatidylcholine unilamellar vesicles made by extrusion technique (LUVETs) were studied as the delivery system for lipophilic water‐insoluble potential photosensitizers for photodynamic therapy (PDT). Two azaphthalocyanines (AzaPcs) with hydrophobic substituents only and two also possessing two charged amino groups were introduced into the study. All compounds are insoluble in water and form aggregates in PBS with tetrahydrofuran as cosolvent. The size of these aggregates depends on the concentration of AzaPc in solution. AzaPcs with tert‐butyl substituents were found to be incorporated into the lipid bilayer of vesicles in the monomeric form even at high concentrations. The stability of LUVETs with incorporated AzaPc was excellent for at least 4 weeks. Therefore, they are suitable for use as a delivery system for these water‐insoluble photosensitizers. Very low amount of AzaPc with n‐octyl substituents incorporated into LUVETs due to its stronger self‐aggregation. Values of binding constants determined for all AzaPcs showed inverse order than expected from their lipophilicities. However, the binding constants followed the order of the strength of aggregation forces. Aggregation of AzaPcs in water medium plays a very important role in the interaction of AzaPcs with LUVETs.
Proton and 31-phosphorus neurospectroscopy in the study of membrane phospholipids and fatty acid intervention in schizophrenia, depression, chronic fatigue syndrome (myalgic encephalomyelitis) and dyslexia

Summary Neurospectroscopy allows biochemical processes in the brain to be studied non-invasively. At magnetic field strengths of 1.5 T or higher, cerebral proton neurospectroscopy allows the ascertainment of values of myo-inositol, choline-containing compounds, creatine, glutamate, glutamine, and N-acetyl aspartate. At similar field strengths, cerebral 31-phosphorus neurospectroscopy allows the ascertainment of values of phosphomonoesters, inorganic phosphate, phosphodiesters, phosphocreatine, and the gamma, alpha and beta nucleotide triphosphate (mainly adenosine triphosphate) resonances. Since choline is a common polar head group at the Sn3 position of membrane phospholipid molecules, a raised level of free choline, as indexed by proton neurospectroscopy, can indicate relatively low anabolism of membrane phospholipid molecules. Furthermore, the choline peak includes phosphorylcholine and glycerophosphorylcholine and even ethanolamine. The phosphomonoesters peak measured using 31-phosphorus spectroscopy includes major contributions from phosphocholine, phosphoethanolamine and L-phosphoserine, which are important precursors of membrane phospholipids, while the phosphodiesters peak includes contributions from glycerophosphocholine and glycerophosphoethanolamine, which are important products of membrane phospholipid catabolism. Hence proton neurospectroscopy and 31-phosphorus neurospectroscopy can yield important information relating to the metabolism of cerebral membrane phospholipids. The application of these techniques to the investigation of membrane phospholipid metabolism in schizophrenia, depression, chronic fatigue syndrome (myalgic encephalomyelitis or M.E.) and dyslexia is described.