Miracle-dz/UniFAR-FTUs huggingface dataset:
On the HUNT for cardiovascular risk factors and disease in patients with psoriatic arthritis: population-based data from the Nord-Trøndelag Health Study

Objective To compare the presence of cardiovascular (CV) risk factors and established CV disease in patients with psoriatic arthritis (PsA) and the general population and to compare the 10-year risk of a fatal CV event calculated by the Systematic Coronary Risk Evaluation (SCORE) algorithm. Methods Patients with PsA (n=338) and controls (n=50 468) were recruited from the Nord-Trøndelag Health Study 3. Age-adjusted and sex-adjusted prevalence rates of CV risk factors and comorbidity were calculated and the SCORE algorithm was applied. Results There was an increased prevalence of angina pectoris (5.0% vs 3.6%, p=0.01), history of percutaneous coronary intervention (2.4% vs 1.4%, p=0.04), hypertension (45.3% vs 39.3%, p=0.01), obesity (32.0% vs 22.4%) and tobacco smoking (21.3% vs 16.4%, p=0.02) in patients with PsA compared with controls. Patients with PsA had elevated levels of C reactive protein (CRP; p<0.001), body mass index (BMI; p<0.001) and triglycerides (p=0.01). The median calculated CV risk in patients with PsA was low and comparable with controls (0.87 vs 0.83, p=0.24). The distribution across CV risk classes was similar among patients with PsA and controls. Conclusions Patients with PsA have a higher risk of CV disease than the background population, although there was no difference between groups in 10-year risk of a fatal CV event estimated by SCORE. However, patients with PsA had elevated levels of CV risk factors not included in the SCORE algorithm, such as BMI, triglycerides and CRP.
Bioelectromagnetic medicine: The role of resonance signaling

Only recently has the critical importance of electromagnetic (EM) field interactions in biology and medicine been recognized. We review the phenomenon of resonance signaling, discussing how specific frequencies modulate cellular function to restore or maintain health. The application of EM-tuned signals represents more than merely a new tool in information medicine. It can also be viewed in the larger context of EM medicine, the all-encompassing view that elevates the EM over the biochemical. The discovery by Zhadin that ultrasmall magnetic intensities are biologically significant suggests that EM signaling is endogenous to cell regulation, and consequently that the remarkable effectiveness of EM resonance treatments reflects a fundamental aspect of biological systems. The concept that organisms contain mechanisms for generating biologically useful electric signals is not new, dating back to the nineteenth century discovery of currents of injury by Matteucci. The corresponding modern-day version is that ion cyclotron resonance magnetic field combinations help regulate biological information. The next advance in medicine will be to discern and apply those EM signaling parameters acting to promote wellness, with decreasing reliance on marginal biochemical remediation and pharmaceuticals.
Investigation of potential targets of Porphyromonas CRISPRs among the genomes of Porphyromonas species

The oral bacterial species Porphyromonas gingivalis, a periodontal pathogen, has plastic genomes that may be driven by homologous recombination with exogenous deoxyribonucleic acid (DNA) that is incorporated by natural transformation and conjugation. However, bacteriophages and plasmids, both of which are main resources of exogenous DNA, do not exist in the known P. gingivalis genomes. This could be associated with an adaptive immunity system conferred by clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated (cas) genes in P. gingivalis as well as innate immune systems such as a restriction-modification system. In a previous study, few immune targets were predicted for P. gingivalis CRISPR/Cas. In this paper, we analyzed 51 P. gingivalis genomes, which were newly sequenced, and publicly available genomes of 13 P. gingivalis and 46 other Porphyromonas species. We detected 6 CRISPR/Cas types (classified by sequence similarity of repeat) in P. gingivalis and 12 other types in the remaining species. The Porphyromonas CRISPR spacers with potential targets in the genus Porphyromonas were approximately 23 times more abundant than those with potential targets in other genus taxa (1,720/6,896 spacers vs. 74/6,896 spacers). Porphyromonas CRISPR/Cas may be involved in genome plasticity by exhibiting selective interference against intra- and interspecies nucleic acids.
Voting in Open Economies

What are the electoral consequences of global market integration? Although recent discussions of politics and markets have much to say on globalization’s implications for policy outcomes, the impact of market integration on representative democracy has received scant attention. This article addresses this omission. We extend the globalization literature to develop two competing hypotheses regarding the influence of open economies on electoral accountability. Predictions are tested using a new data set covering elections from 75 countries over 27 years. Results support a government constraint hypothesis: Exposure to the world economy weakens connections between economic performance and support for political incumbents. By redirecting concerns from the policy implications of globalization and toward its electoral consequences, findings highlight the influence of voter perceptions and of vote-seeking politicians in the politics of globalization.
A human Na+/H+ antiporter sharing evolutionary origins with bacterial NhaA may be a candidate gene for essential hypertension

Phylogenetic analysis of the cation/proton antiporter superfamily has uncovered a previously unknown clade of genes in metazoan genomes, including two previously uncharacterized human isoforms, NHA1 and NHA2, found in tandem on human chromosome 4. The NHA (sodium hydrogen antiporter) family members share significant sequence similarity with Escherichia coli NhaA, including a conserved double aspartate motif in predicted transmembrane 5. We show that HsNHA2 (Homo sapiens NHA2) resides on the plasma membrane and, in polarized MDCK cells, localizes to the apical domain. Analysis of mouse tissues indicates that NHA2 is ubiquitous. When expressed in the yeast Saccharomyces cerevisiae lacking endogenous cation/proton antiporters and pumps, HsNHA2 can confer tolerance to Li+ and Na+ ions but not to K+. HsNHA2 transformants accumulated less Li+ than the salt-sensitive host; however, mutagenic replacement of the conserved aspartates abolished all observed phenotypes. Functional complementation by HsNHA2 was insensitive to amiloride, a characteristic inhibitor of plasma membrane sodium hydrogen exchanger isoforms, but was inhibited by phloretin. These are hallmarks of sodium–lithium countertransport activity, a highly heritable trait correlating with hypertension. Our findings raise the possibility that NHA genes may contribute to sodium–lithium countertransport activity and salt homeostasis in humans.
Developmental potential of rhesus monkey embryos produced by in vitro fertilization.

This study was an examination of the developmental potential of in vitro fertilization (IVF)-produced rhesus monkey embryos that were cultured in medium alone or cocultured with various cell types. End points were the quality and yield of embryos attaining the expanded or hatched blastocyst stage. A total of 96 IVF-produced embryos were cryopreserved and thawed, and 90 embryos were considered intact and suitable for culture. These embryos were placed into one of five treatment groups consisting of four different cell supports and medium alone. Two primary cultures (bovine oviductal cells [bOVID] and bovine cumulus cells [bCUM]) and two established cell lines (Vero cells and buffalo rat liver cells [BRL]) were utilized for coculture of embryos. Embryos were cultured for up to 14 days, and growth curves were established for all embryos that expanded and/or hatched. The developmental rate for embryos classified as viable varied substantially; in number of days to reach a given stage, early morulae ranged from Days 3 to 9 post-insemination, morulae from Days 4 to 9, blastocysts from Days 6 to 11, expanded blastocysts from Days 7 to 12, and hatched blastocysts from Days 9 to 15. On the basis of developmental curves, 30% of the embryos were arrested upon thawing or shortly after. Of the remaining embryos classified as viable, developmental efficiencies to the hatched blastocyst stage for the various treatments were 1) bOVID, 33%; 2) bCUM, 15%; 3) Vero cells, 9%; 4) BRL, 45%; and 5) medium alone, 8%. (ABSTRACT TRUNCATED AT 250 WORDS)
Sulfur Mustard-Induced Apoptosis in Hairless Guinea Pig Skin

The present study was aimed to examine whether apoptosis is involved in the pathogenesis of sulfur mustard (SM)-induced basal cell death. Skin sites of the hairless guinea pig exposed to SM vapor for 8 minutes were harvested at 3, 6, 12, 24, and 48 hours postexposure. Immunohistochemical detection of basal cell apoptosis was performed using the ApopTag in situ apoptosis labeling kit. Only occasional apoptotic basal cells (BC) were observed in nonexposed and perilesional control sites. At lesional sites, apoptosis of BC was not detected at 3 hours postexposure. However, at 6 hours and 12 hours postexposure, 18% and 59% of BC were apoptotic, respectively. At 24 and 48 hours postexposure, individual apoptotic basal cells were not clearly recognizable due to necrosis. At the ultrastructural level, degenerating BC exhibited typical apoptotic morphology including nuclear condensation and chromatin margination. The results suggest that apoptotic cell death is a cytotoxic mechanism with the number of BC undergoing apoptosis significantly increasing from 6 to 12 hours postexposure. In addition, because necrosis is preferential at 24 hours postexposure, we believe that SM-induced cell death involves early apoptosis and late necrosis, which temporally overlap to produce a single cell death pathway along an apoptotic-necrotic continuum.
Connected Kids at Head Start: Taking Office-Based Violence Prevention to the Community

OBJECTIVE: The goal was to assess the acceptability and appropriateness of using a violence prevention curriculum, Connected Kids: Safe, Strong, Secure, at Head Start centers. METHODS: Eight 90-minute focus groups (4 parent groups and 4 family advocate groups) were conducted at 2 Head Start centers. Each discussion was audiotaped, transcribed, and analyzed for major themes. RESULTS: A total of 63 adults (38 family advocates [92% female] and 25 parents [100% female]) participated in the 8 groups. Family advocates and parents agreed that Head Start was an important source of parenting advice and of referrals to community resources. Connected Kids topics were well received, although potential parental resistance to gun safety and discipline materials was identified. The positive nature of the advice was important to both types of groups. Brochures were generally well liked, but all groups thought that they should be linked directly to community resource information and offered as part of tailored education. Various venues for curriculum use were suggested, and formats involving multiple media were requested. Although Head Start serves preschool-aged children, parents and family advocates valued access to the full range of Connected Kids materials (for ages 0–18 years). Family advocates emphasized that supplementary materials on background information and delivery methods would be essential for effective implementation of Connected Kids at Head Start. CONCLUSIONS: Head Start family advocates and parents found the Connected Kids curriculum desirable. Although modifications might improve its usefulness, the curriculum seems acceptable and appropriate for the Head Start environment.
De novo transcriptome assembly of a fern, Lygodium japonicum, and a web resource database, Ljtrans DB.

During plant evolution, ferns originally evolved as a major vascular plant with a distinctive life cycle in which the haploid and diploid generations are completely separated. However, the low level of genetic resources has limited studies of their physiological events, as well as hindering research on the evolutionary history of land plants. In this study, to identify a comprehensive catalog of transcripts and characterize their expression traits in the fern Lygodium japonicum, nine different RNA samples isolated from prothalli, trophophylls, rhizomes and sporophylls were sequenced using Roche 454 GS-FLX and Illumina HiSeq sequencers. The hybrid assembly of the high-quality 454 GS-FLX and Illumina HiSeq reads generated a set of 37,830 isoforms with an average length of 1,444 bp. Using four open reading frame (ORF) predictors, 38,142 representative ORFs were identified from a total of 37,830 transcript isoforms and 95 contigs, which were annotated by searching against several public databases. Furthermore, an orthoMCL analysis using the protein sequences of L. japonicum and five model plants revealed various sets of lineage-specific genes, including those detected among land plant lineages and those detected in only L. japonicum. We have also examined the expression patterns of all contigs/isoforms, along with the life cycle of L. japonicum, and identified the tissue-specific transcripts using statistical expression analyses. Finally, we developed a public web resource, the L. japonicum transcriptome database at http://bioinf.mind. meiji.ac. jp/kanikusa/, which provides important opportunities to accelerate molecular research in ferns.
Cell Toxicity Induced by Inhibition of Acyl Coenzyme A:Cholesterol Acyltransferase and Accumulation of Unesterified Cholesterol *

Considerable evidence supports the involvement of acyl-CoA:cholesterol acyltransferase (ACAT) in the maintenance of intracellular cholesterol homeostasis. A number of recently developed ACAT inhibitors may have potential use as pharmacological agents to reduce the development of atherosclerosis. Recently, however, reports arose describing cytotoxic effects following administration of a specific ACAT inhibitor to experimental animals. In order to address the specific intracellular mechanisms involved with the cytotoxic effect, we examined the consequences of ACAT inhibition in cholesterol-enriched mouse peritoneal macrophages. Mouse peritoneal macrophages were cholesterol-enriched by incubation with acetylated low density lipoprotein and free cholesterol:phospholipid dispersions prior to the addition of an ACAT inhibitor, either Sandoz 58-035 or Pfizer CP-113,818. The adenine pool of the macrophages was radiolabeled prior to addition of the ACAT inhibitors, in order to monitor the release of radiolabeled adenine, a technique shown to be a sensitive method to monitor drug-induced toxicity. The ACAT inhibitors were added for up to 48 h and at concentrations up to 2 μg/ml. These conditions resulted in an approximately 2-fold increase in adenine release. The increase in cell toxicity paralleled an increase in the cellular free cholesterol content. Reducing the cellular free cholesterol content, by the addition of extracellular acceptors, decreased the cytotoxic effects of the ACAT inhibitors. Addition of an intracellular cholesterol transport inhibitor, either progesterone or U18666A, together with CP-113,818 blocked the toxic effect of CP-113,818. These results suggest that ACAT inhibition of cholesterol-enriched macrophages increases cell toxicity due to the buildup of cellular free cholesterol. Removal of free cholesterol by the addition of extracellular cholesterol acceptors or by blocking intracellular sterol transport relieves the ACAT inhibitor-induced toxicity.
Initial Experience With Gallium-68 DOTA-Octreotate PET/CT and Peptide Receptor Radionuclide Therapy for Pediatric Patients With Refractory Metastatic Neuroblastoma

Rationale:Pediatric patients with refractory neuroblastoma have limited therapeutic options. Neuroblastoma may express somatostatin receptors (SSTRs) allowing imaging with 68Ga-DOTA-Octreotate (GaTATE) positron emission tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy (PRRT). We reviewed our experience with this theranostic combination. Materials and Methods:GaTATE studies (8 patients; 2 to 9 years old) were reviewed and compared with 123I-MIBG or posttreatment 131I-MIBG studies. Immunohistochemistry (IHC) for SSTR subtype 2 was performed in 5 patients. Four patients received PRRT. Results:GaTATE PET showed additional disease in 38% (3/8 patients), and upstaged 1 patient by detecting marrow involvement. IHC detected SSTR 2 in all patients assessed. Six patients were deemed suitable for PRRT on imaging. Four patients received 17 cycles of palliative PRRT (10 111In-DOTATATE; 5 177Lu-DOTATATE; 1 combined 111In and 177Lu-DOTATATE; 1 combined 177Lu and 90Y-DOTATATE) with no significant toxicity attributed to PRRT. All had objective responses. Two survivors are now 40 and 56 months from PRRT commencement. Conclusions:GaTATE PET was positive in a high proportion of patients with refractory neuroblastoma, correlating with SSTR 2 on IHC, with additional disease identified compared with MIBG imaging. PRRT seems safe, feasible, with responses observed in patients with progression despite multimodality treatment. These data support ongoing clinical trials in such patients.
Predictors of mortality in men and women aged 90 and older: a nine-year follow-up study in the Vitality 90+ study.

BACKGROUND information about the predictors of mortality among the oldest-old is limited. Also possible gender differences are poorly known. OBJECTIVE to examine the predictors of mortality among individuals aged 90 and older, focusing on differences between men and women. We also analysed gender differences in survival at different levels of mobility and activities in daily living (ADL). DESIGN this 9-year follow-up study is part of the Vitality 90+ study, a population-based study of people aged 90 and older. SUBJECTS all inhabitants aged 90 and older in the area of Tampere, Finland were contacted, irrespective of health or dwelling place. The study population consisted of 171 men and 717 women. METHODS data were collected with a mailed questionnaire asking questions concerning ADL and mobility, self-rated health, chronic conditions and socio-economic factors. The participation rate was 79%. Cox regression enter models were used for the analysis. RESULTS older age, male gender, disability in ADL and mobility, poor self-rated health and institutionalisation increased the risk of mortality in the total study group. In age-adjusted Cox regression models, ADL and mobility were stronger predictors in men than in women (gender interactions, P < 0.001). Among those who were partly but not totally dependent in ADL or mobility women survived longer than men. CONCLUSION the same health indicators that are important at younger old age also predict mortality in the oldest-old. Disability increases the likelihood of death more in men than women. At a very old age, women survive longer with moderate disability than do men.
Biochemistry and Comparative Genomics of SxxK Superfamily Acyltransferases Offer a Clue to the Mycobacterial Paradox: Presence of Penicillin-Susceptible Target Proteins versus Lack of Efficiency of Penicillin as Therapeutic Agent

SUMMARY The bacterial acyltransferases of the SxxK superfamily vary enormously in sequence and function, with conservation of particular amino acid groups and all-α and α/β folds. They occur as independent entities (free-standing polypeptides) and as modules linked to other polypeptides (protein fusions). They can be classified into three groups. The group I SxxK d,d-acyltransferases are ubiquitous in the bacterial world. They invariably bear the motifs SxxK, SxN(D), and KT(S)G. Anchored in the plasma membrane with the bulk of the polypeptide chain exposed on the outer face of it, they are implicated in the synthesis of wall peptidoglycans of the most frequently encountered (4→3) type. They are inactivated by penicillin and other β-lactam antibiotics acting as suicide carbonyl donors in the form of penicillin-binding proteins (PBPs). They are components of a morphogenetic apparatus which, as a whole, controls multiple parameters such as shape and size and allows the bacterial cells to enlarge and duplicate their particular pattern. Class A PBP fusions comprise a glycosyltransferase module fused to an SxxK acyltransferase of class A. Class B PBP fusions comprise a linker, i.e., protein recognition, module fused to an SxxK acyltransferase of class B. They ensure the remodeling of the (4→3) peptidoglycans in a cell cycle-dependent manner. The free-standing PBPs hydrolyze d,d peptide bonds. The group II SxxK acyltransferases frequently have a partially modified bar code, but the SxxK motif is invariant. They react with penicillin in various ways and illustrate the great plasticity of the catalytic centers. The secreted free-standing PBPs, the serine β-lactamases, and the penicillin sensors of several penicillin sensory transducers help the d,d-acyltransferases of group I escape penicillin action. The group III SxxK acyltransferases are indistinguishable from the PBP fusion proteins of group I in motifs and membrane topology, but they resist penicillin. They are referred to as Penr protein fusions. Plausible hypotheses are put forward on the roles that the Penr protein fusions, acting as l,d-acyltransferases, may play in the (3→3) peptidoglycan-synthesizing molecular machines. Shifting the wall peptidoglycan from the (4→3) type to the (3→3) type could help Mycobacterium tuberculosis and Mycobacterium leprae survive by making them penicillin resistant.
Birthweight and Body Mass Index in Young Adulthood: The Swedish Young Male Twins Study

Abstract Many studies have found an inverse association between fetal growth and cardiovascular disease related to the metabolic syndrome in adulthood. Nevertheless, the relative importance of genetics and the intrauterine environment remain unclear. The objective of the study was to test the fetal origins hypothesis and the fetal insulin resistance hypothesis by studying the impact of fetal growth on Body Mass Index (BMI) in young adulthood. In a nationwide cohort study, the Swedish Medical Birth Register for the years 1973–1979 was linked with the Military Service Conscription Register for 1990–1999. In 1998 a questionnaire was mailed to all male twins, included in the two registers, who were alive and still resident in Sweden. The study covers the 923 male twin pairs for which full data were available. Mixed linear models were used to estimate within-pair and between-pair differences in birthweight and their relations to BMI. A weak positive association was found among the monozygotic twins for the withinpair difference in birthweight and BMI. No significant association was found among the monozygotic for the between-pair difference in birthweight and BMI. No significant associations were found for dizygotic twins. These findings do not seem to support either the fetal programming hypothesis or the fetal insulin resistance hypothesis.