Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel (2E,4E,6Z)-7-(2-alkoxy-3,5-dialkylbenzene)-3-methylocta-2,4,6-trienoic acid retinoid X receptor modulators are active in models of type 2 diabetes.

Previous data have shown that RXR-selective agonists (e.g., 3 and 4) are insulin sensitizers in rodent models of non-insulin-dependent diabetes mellitus (NIDDM). Unfortunately, they also produce dramatic increases in triglycerides and profound suppression of the thyroid hormone axis. Here we describe the design and synthesis of new RXR modulators that retain the insulin-sensitizing activity of RXR agonists but produce substantially reduced side effects. These molecules bind selectively and with high affinity to RXR and, unlike RXR agonists, do not activate RXR homodimers. To further evaluate the antidiabetic activity of these RXR modulators, we have designed a concise and systematic structure-activity relationship around the 2E,4E,6Z-7-aryl-3-methylocta-2,4,6-trienoic acid scaffold. Selected compounds have been evaluated using insulin-resistant rodents (db/db mice) to characterize effects on glucose homeostasis. Our studies demonstrate the effectiveness of RXR modulators in lowering plasma glucose in the db/db mouse model.
Oral health, medical diagnoses, and functioning profiles in children with disabilities receiving paediatric specialist dental care – a study using the ICF-CY

Abstract Purpose: To describe 0–16-year-old children with disabilities receiving paediatric specialist dental care from a biopsychosocial perspective, with focus on relationship between oral health, medical diagnosis, and functioning. Method: A questionnaire with an International Classification of Functioning, Disability and Health – Children and Youth version (ICF-CY) Checklist for Oral Health was completed using structured interview, direct observation, and information from dental records. Descriptive data analysis was performed together with principle component analysis to calculate factors of functioning used in cluster analysis in order to present functioning profiles. Results: Ninety-nine children with at least one major medical diagnosis were included. Twenty had previous caries experience. Two factors of functioning were calculated, labelled “Physical ability” and “Intellectual ability, communication, and behaviour”. Based on functioning profiles three clusters were determined. There were no statistically significant differences in caries experience between medical diagnoses or clusters. Conclusion: It was possible to identify profiles of functioning in children with disabilities receiving specialist dental care. Despite complex disabilities, the children had good oral health. Neither medical diagnosis nor functioning was found to have a clear relationship with oral health. To understand the environmental context leading to high-quality oral health, further studies of dental management in relation to medical and oral diagnoses and child functioning are needed. Implications for Rehabilitation Child Oral Health The use of ICF-CY makes it possible for paediatric dentists to assess children’s functioning, disability, and health from a biopsychosocial perspective, showing that the medical diagnosis alone is not enough to assess functions relevant for oral health in the individual. In order to adequately organize, plan, and improve dental care for this heterogenic group of young patients with disabilities a biopsychosocial approach is valuable, aiding a holistic perspective on oral health. Despite complex medical and functional disabilities that may challenge oral health and dental care, this study finds oral health to be good in a group of children with disabilities attending a specialist dental clinic.
Identification of the capsule type of Pasteurella multocida isolates from cases of fowl cholera by multiplex PCR and comparison with phenotypic methods

The ability of Pasteurella multocida to invade and multiply in its host is enhanced by the presence of the capsule, one of the most important virulence factors for this bacterium. Capsular typing methods are often used in epidemiological and pathogenesis studies of this agent. Five different serogroups have been identified based on serological typing. However, such tests are laborious, and agglutination of homologous antiserum may fail. The aim of this study was to develop a multiplex PCR protocol for the identification of the hyaD-hyaC and dcbF genes specific to serogroups A and D, respectively, and to compare these results with those of phenotypic tests for 54 strains isolated from fowl cholera cases in southern Brazil. The kappa coefficient and chisquare statistics were calculated to assess the agreement between the diagnostic methods and to determine the significance of the results, respectively. The multiplex PCR was able to detect the evaluated genes. Forty-nine strains (90.74%) were classified into serogroup A, and only two isolates (3.7%) were not identified as belonging to any of the serogroups analyzed. In contrast, with the phenotypic tests, only 41 strains (75.93%) were classified into serogroup A and 11 samples (20.37%) were unidentifiable. Of the strains analyzed, 70.37% were classified into the same serogroup (A) by both methods, and the kappa coefficient (k = 0.017) indicated poor agreement between the tests. Thus, multiplex PCR is an alternative for P. multocida capsular typing, as it allows the simultaneous and rapid detection of genes and also provides a greater strain-typing capacity.
Quantitation of in vivo human folate metabolism 1–3

Background: A quantitative understanding of human folate metabolism is needed. Objective: The objective was to quantify and interpret human folate metabolism as it might occur in vivo. Design: Adults ( n (cid:1) 13) received 0.5 nmol [ 14 C]pteroylmonoglu-tamate (100 nCi radioactivity) plus 79.5 nmol pteroylmonoglutamate in water orally. 14 C was measured in plasma, erythrocytes, urine,andfecesfor (cid:2) 40d.Kineticmodelingwasusedtoanalyzeand interpret the data. Results: According to the data, the population was healthy and had a mean dietary folate intake of 1046 nmol/d, and the apparent dose absorption of 14 C was 79%. The model predictions showed that only 0.25% of plasma folate was destined for marrow, mean bile folate flux was 5351 nmol/d, and the digestibility of the mix (1046 (cid:3) 5351 nmol/d) was 92%. About 33% of visceral pteroylmonoglutamate was converted to the polyglutamate form, most of the body folate was visceral ( (cid:4) 99%), most of the visceral folate was pteroylpolyglutamate ( (cid:4) 98%), total body folate was 225 (cid:1) mol, and pteroylpolyglutamate synthesis, recycling, and catabolism were 1985, 1429, and 556 nmol/d, respectively. Mean residence times were 0.525 d as visceral pteroylmonoglutamate, 119 d as visceral pteroylpolyglutamate, 0.0086 d as plasma folate, and 0.1 d as gastrointestinal folate. Conclusions: Across subjects, folate absorption, bile folate flux, and body folate stores were larger than prior estimates. Marrow folate uptake and pteroylpolyglutamate synthesis, recycling, and catabolism are saturable processes. Visceral pteroylpolyglutamate was an immediate precursor of plasma p -aminobenzoylglutamate. The model is a working hypothesis with derived features that are explicitly model-dependent. It successfully quantitated folate metabolism, encouraging further rigorous testing. A limitation of the previous studies was that all but one (16) were of short duration (7 d), thus the isotopes may not have equilibrated fully in body folate pools that turn over the slowest (6–9, 11–15). Because these pools can become key determinants of folate metabolism late in a study, we used accelerator mass spectrometry (AMS) (17) to follow an oral dose of [ 14 C]pteroyl-monoglutamate in 13 healthy adults for longer periods than in previous studies. We used kinetic modeling (18–21) of the data set to quantify and interpret folate metabolism as it might occur in vivo.
Angiogenesis and Lymphangiogenesis—Implications for Corneal Immunity

It is now widely acknowledged that vasculogenesis and immunogenic inflammation are intricately related in many tissues. However, less understood is to what extent blood (heme) angiogenesis (HA) and lymphangiogenesis (LG) are differentially regulated, and in turn contribute potentially to different aspects of adaptive immunity generated to corneal antigens. Herein, we will provide a brief synopsis of relevant work in this field by focusing particularly on the differential regulation of immunity by these two distinct vasculogenic processes in the cornea, illustrating that in spite of significant redundancies in the mechanisms that induce these vascular processes in the cornea, there are also important distinctions in what aspects of immunity are promoted by them. keywords
Cities in ‘multiple globalizations’: insights from the upstream oil and gas World City Network

ABSTRACT The role of cities in the global economy has been studied extensively for the specific case of advanced producer services. Only recently, studies started to broaden the analytical lens and explore the role of cities in ‘multiple globalizations’ by adding insights from other industries. Apart from showing that different World City Networks (WCNs) are characterized by differing spatial configurations, these studies are incapable of explaining why cities have been articulated into a particular WCN. Building on a case study of Singapore and Jakarta in the WCN of the upstream oil and gas industry, the study demonstrates the potential gained by adding flesh to the study of cities in ‘multiple globalizations’ through qualitative insights. The findings reveal how very different state roles have contributed to the shape of this particular WCN. The paper thereby illustrates how this recent field of research on cities in ‘multiple globalizations’ may advance beyond the mere description of city network structures.
Family Story on Land-Related Tradition as Base for Land-Use Management and Sustainable Development: The Case of Indigenous Mentawai

Indonesian government is actively developing the indigenous villages of Mentawai. The development has brought social conflict over land and ineffective development due to the ignorance of the indigenous tradition on land. The indigenous people have a fanatically practiced tradition recorded in their family stories from which social norms on land are basically derived. Unfortunately, previous studies on the tradition in which there are rituals and taboos as the base for land-use management and development remains ignored and unexamined. The paper examines indigenous land-related tradition in village of Madobag Mentawai as basic social norms for indigenous land-use management and development. Its objectives are to identify indigenous social norms based on the tradition for possible land-use management and sustainable development. The study applies ethnography method based on theoretical approach of indigenous tradition and taboo on land. The result is that the indigenous people have a number of land-related traditions in which it is found rituals, taboos, sacred sites, and food, medical and ritual plants, plants for traditional home and canoe, and culturally important hunting area. The traditions include indigenous land-ownership, land-use for the indigenous, land-use for outsiders, and land-use for development. The traditions are social norms which should be seriously considered as base for land-use management and sustainable development. They can be as effective base for indigenous land-use management and development policy in using the land, solving social conflict over land, keeping social harmony, making policy on development, conserving environment and forest, and preserving indigenous Mentawai culture.
Antibiotic Production by Myxobacteria Plays a Role in Predation

ABSTRACT Myxobacteria are predatory and are prolific producers of secondary metabolites. Here, we tested a hypothesized role that secondary metabolite antibiotics function as weapons in predation. To test this, a Myxococcus xanthus Δta1 mutant, blocked in antibiotic TA (myxovirescin) production, was constructed. This TA− mutant was defective in producing a zone of inhibition (ZOI) against Escherichia coli. This shows that TA is the major M. xanthus-diffusible antibacterial agent against E. coli. Correspondingly, the TA− mutant was defective in E. coli killing. Separately, an engineered E. coli strain resistant to TA was shown to be resistant toward predation. Exogenous addition of spectinomycin, a bacteriostatic antibiotic, rescued the predation defect of the TA− mutant. In contrast, against Micrococcus luteus the TA− mutant exhibited no defect in ZOI or killing. Thus, TA plays a selective role on prey species. To extend these studies to other myxobacteria, the role of antibiotic corallopyronin production in predation was tested and also found to be required for Corallococcus coralloides killing on E. coli. Next, a role of TA production in myxobacterial fitness was assessed by measuring swarm expansion. Here, the TA− mutant had a specific swarm rate reduction on prey lawns, and thus reduced fitness, compared to an isogenic TA+ strain. Based on these observations, we conclude that myxobacterial antibiotic production can function as a predatory weapon. To our knowledge, this is the first report to directly show a link between secondary metabolite production and predation.
Proteolytic Processing and Oligomerization of Bacteriophage-derived Endosialidases*

Bacteriophages infecting the neuroinvasive pathogen Escherichia coli K1 require an endosialidase to penetrate the polysialic acid capsule of the host. Sequence information is available for the endosialidases endoNE, endoNF, and endoN63D of the K1-specific phages φK1E, φK1F, and 63D, respectively. The cloned sequences share a highly conserved catalytic domain but differ in the length of the N- and C-terminal parts. Although the expression of active recombinant enzyme succeeded in the case of endoNE, it failed for endoNF. Protein alignments of all three endosialidase sequences gave rise to the assumption that inactivity of the cloned endoNF is caused by a C-terminal truncation. By reinvestigation of the respective gene locus in the φK1F genome, we identified an extended open reading frame of 3195 bp, encoding a 119-kDa protein. Full-length endoNF contains the C-terminal domain conserved in all endosialidases, which may act as an intramolecular chaperone. Comparative studies carried out with endoNE and endoNF demonstrate that endosialidases are proteolytically processed, releasing the C-terminal domain. Using a mutational approach in combination with protein analytical techniques we demonstrate that (i) the C-terminal domain is a common feature of endosialidases and other tail fiber proteins; (ii) the integrity of the C-terminal domain and its presence in the nascent protein are crucial for the formation of active enzymes; (iii) proteolytic processing is not essential for enzymatic activity; and (iv) functional folding is a prerequisite for trimerization of endoNF.
Highway driving performance and cognitive functioning the morning after bedtime and middle‐of‐the‐night use of gaboxadol, zopiclone and zolpidem

Gaboxadol is a selective extrasynaptic GABAA receptor agonist previously in development for the treatment of insomnia. Due to its short half‐life (1.5–2 h) it is expected to be free from residual effects the next morning. The present study assessed the residual effects of evening and middle‐of‐the‐night administration of 15 mg of gaboxadol on cognitive, psychomotor and driving performance. Twenty‐eight healthy volunteers entered the study with 25 (12 women; mean age 31.4 years) completing a double‐blind, placebo‐controlled, active‐referenced five‐way cross‐over study. Each treatment night subjects ingested one capsule at 23:00 hours and one at 04:00 hours. Treatments were placebo at both times, 15 mg gaboxadol or 7.5 mg zopiclone followed by placebo, and placebo followed by 15 mg gaboxadol or 10 mg zolpidem. Effects on cognition and psychomotor performance were assessed between 07:30 and 08:30 hours and on driving between 09:00 and 10:00 hours. Driving, as measured by standard deviation of lateral position in an on‐the‐road driving test, was almost significantly (P < 0.07) impaired after evening administration of gaboxadol for the all‐subjects‐completed set (n = 25) but significantly (P < 0.05) in the full analysis set (n = 28). Effects of all other active treatments on driving were significant. Evening administration of gaboxadol had minor effects on divided attention only, whereas middle‐of‐the‐night administration impaired performance significantly in all tests except memory. Zolpidem and zopiclone impaired performance significantly in every test except tracking after zopiclone; 15 mg of gaboxadol can produce minor residual effects on driving after evening administration. Administration later at night is associated with moderately impairing residual effects on driving and psychomotor performance but not on memory.
Foraging energetics of a nectar-feeding ant: metabolic expenditure as a function of food-source profitability

SUMMARY We examined the quantitative relationship between the energetic costs and benefits of nectar collection by nectar-feeding ants, Camponotus rufipes. In the laboratory, individual workers were trained to visit an artificial feeder that provided a sucrose solution of 1%, 5%, 10%, 30% or 50% at controlled flows, in a similar span range to those observed in natural nectar sources. We measured foraging times, nectar loads collected, and CO2 production during actual feeding, as an indication of the energy expenditure for a single forager. Results show an increase in individual metabolic rates with increasing flow rate of sugar solution, but no dependence on sucrose concentration. This increase in metabolic expenditure does not depend on the crop load attained while feeding, as intuitively expected, and is therefore a result of an increased activity brought about by the food-source profitability experienced by the forager. The energy gained during collection of sugar solution is always higher than the energy spent by the ant. Even with a food source of lower quality than a natural source, the ants gain ca. tenfold of what they spend. Based on a simplified model, we calculated that foragers of C. rufipes could travel from 0.5 to 9 km with the energy gained in a single foraging trip only. These results suggest that decreasing foraging time is more important than increasing individual energetic efficiency when workers of the nectar-feeding ant C. rufipes decide to stop drinking and return to the nest with partial crop loads.
Two New Solanapyrone Analogues from the Endophytic Fungus Nigrospora sp. YB‐141 of Azadirachta indica

Two new solanapyrone analogues, solanapyrones N and O (1 and 2, resp.), and three known compounds, solanapyrone C (3), nigrosporalactone (4), and phomalactone (5), were isolated from the fermentation culture of Nigrospora sp. YB-141, an endophytic fungus isolated from Azadirachta indica A. Juss. The structures of the new compounds were elucidated on the basis of spectroscopic analysis. The antifungal activities of 1-5 towards seven phytopathogenic fungi were tested. Most of the compounds exhibited no or only weak antifungal activities.
Androgen receptor (AR) in osteocytes is important for the maintenance of male skeletal integrity: Evidence from targeted AR disruption in mouse osteocytes

Androgens play a key role in the maintenance of male skeletal integrity. The regulation of this integrity by androgen receptor (AR) signaling has been mainly attributed to osteoblasts. Although osteocytes have emerged as key regulators of bone remodeling, the influence of sex steroids on these cells has been poorly studied. We aimed to investigate the role of AR signaling, specifically in osteocytes using the Cre/LoxP system in male mice (driven by dentin matrix protein 1 [ocy‐ARKOs]). Osteocyte fractions of control (AR(ex2)/Y) and ocy‐ARKO (ARflox(ex2)/Y; DMP1‐cre) mice isolated through sequential collagenase digestion showed increasing AR expression toward the mature osteocyte fraction of control males compared with the more immature fractions, whereas this was reduced by >80% in ocy‐ARKO osteocytes. The skeletal phenotype of mutant mice was further assessed by histomorphometry and quantitative micro‐computed tomography at 12 and 32 weeks of age. Ocy‐ARKOs had significantly lower trabecular bone volume and number in femora and tibias at 32 weeks as well as decreased trabecular number in the L5 vertebra at 12 weeks. Biomechanical testing showed that ocy‐ARKO femora were also stiffer and required a lower ultimate force to induce failure at 32 weeks. However, femoral cortical structure was not significantly different at any time point. The absence of AR in osteocyte also did not appear to affect trabecular bone formation nor its response to mechanical loading. In conclusion, selective inactivation of the AR in osteocytes of male mice accelerates age‐related deterioration of skeletal integrity. These findings provide evidence for a direct role of androgens in the maintenance of trabecular bone through actions of the AR in osteocytes. © 2012 American Society for Bone and Mineral Research.
YLR209c Encodes Saccharomyces cerevisiae Purine Nucleoside Phosphorylase

ABSTRACT The yeast YLR209c (PNP1) gene encodes a protein highly similar to purine nucleoside phosphorylases. This protein specifically metabolized inosine and guanosine. Disruption ofPNP1 led to inosine and guanosine excretion in the medium, thus showing that PNP1 plays an important role in the metabolism of these purine nucleosides in vivo.
Attracting Students to Sales Positions: The Case of Effective Salesperson Recruitment Ads

Given the recent proliferation in sales programs, business colleges face a new set of challenges. Sales competencies are changing rapidly, and firms struggle with identifying and attracting sales candidates on campus. Therefore, it is important that we understand needed competencies and how the content of job advertisements may differentially appeal to various student populations. To do so, we develop a conceptual model, based on signaling theory, that focuses on how students formulate their intention to pursue a given sales position. Our research utilizes a two-study approach. First, we explore the desired entry-level sales skills communicated by employers through job advertisements. Next, we examine both student and advertisement characteristics and their distinct relationships with the satisfaction with the job ad and the intention to apply for a sales position. Our study is unique, as we examine distinct undergraduate groups’ (sales, marketing, other business, and nonbusiness students) responses to sales job advertisements. Our findings demonstrate that differences in job ad clusters and student group characteristics influence the intention to pursue a sales position. Specifically, different student majors perceive job characteristics communicated within job ads differently. As such, our research provides insight into academic programs as well as corporate sales recruiters.
Corporate Derivatives Usage, Information Environment, and Stock Price Crash Risk

This study investigates the effect of corporate derivatives usage on stock price crash risk. We test two competing hypotheses. Under the transparency hypothesis, derivatives usage reduces information opacity and lowers crash risk. Under the speculation hypothesis, derivatives usage exacerbates managerial short-termism and increases crash risk. We find evidence supporting the transparency hypothesis. This result is robust to sensitivity checks including a two-stage treatment model, difference-in-differences test, and subsample analysis. We further show that curbing bad news hoarding, curtailing overinvestment, and increasing breadth of ownership are potential channels through which derivatives usage mitigates crash risk. Additional tests on the effect of derivatives usage on likelihood of securities class-action litigation provide consistent results.