Miracle-dz/UniFAR-FTUs huggingface dataset:
A population‐based approach to the investigation of osteopenia in Rett syndrome

This study compares bone mass in a national sample of girls with Rett syndrome (RS) with a sample of control children. The Australian RS Database was the source of cases for this population‐based study. Hand radiographs were available from 101 of 137 subjects (74% of the known Australian population of girls with RS aged ? 20 years). Control radiographs matched for age, sex, and laterality were obtained from hospital radiology departments. A measure of cortical thickness was made from the difference between the outer diameter and the medullary space in the second metacarpal bone. A mean z ‐score value for cortical thickness and percentage cortical area for each individual was calculated. The mean cortical thickness (z score) for girls with RS was –1.94 compared with –0.38 for control children (P<0.001). In girls with RS, the mean cortical thickness decreased with age (P<0.001). In girls who were taking epilepsy medication it was –2.21 compared with –1.23 in those not taking epilepsy medication (P<0.001). There was no evidence of a beneficial effect of increased calcium intake on cortical thickness. A similar pattern was obtained when percentage cortical area was estimated. In multivariate analysis, increasing age and use of anticonvulsant medication were associated with decreased cortical thickness and only use of anticonvulsant medication with decreased percentage cortical area. Fractures had occurred in one‐third of cases and it was estimated that just over 40% of girls would sustain a fracture by the age of 15 years. Girls with RS may be at increased risk of fractures and their bone quality compromised as determined by cortical thickness and percentage cortical area measurements from the second metacarpal.
An extended 5′-tau susceptibility haplotype in progressive supranuclear palsy

Objective: To confirm the association of an extended 5′-tau haplotype on chromosome 17q with the disease phenotype in clinically ascertained individuals with sporadic progressive supranuclear palsy (PSP). Background: PSP is a neurodegenerative disease with parkinsonian signs accompanied by vertical supranuclear palsy and tau pathologic features. Previously, we documented the complete segregation of an extended 5′-tau haplotype consisting of four single nucleotide polymorphisms (SNP) with the disease phenotype in sporadic PSP. This study was conducted in an independent cohort to confirm these results and to improve the statistical power of the data. Design and Methods: Direct sequencing and restriction enzyme digests were used to analyze four SNP in tau Exons 1, 4A, and 8. These contiguous SNP were used to reconstruct an extended 5′-tau haplotype in 52 affected and 54 age-matched control individuals. Results: The four SNP formed two homozygous 5′-tau haplotypes (HapA and HapC) or a heterozygous genotype. Fifty-one (98%) patients with PSP had HapA; one (2%) with a later onset was heterozygous; and none had HapC. These PSP haplotype frequencies were different (p < 0.00001) from those of the age-matched control group, in which 18 (33%) people had HapA; 26 (48%) were heterozygous; and 10 (19%) had HapC. The extended 5′-tau haplotype, HapA, had a high sensitivity (98%) and a moderate specificity (67%) as a marker for PSP. Conclusions: A 5′-tau susceptibility haplotype may be a sensitive marker for sporadic PSP and a genetic defect in, or closely linked to, tau may contribute to the cause of PSP.
PLASTICITY TO LIGHT CUES AND RESOURCES IN ARABIDOPSIS THALIANA: TESTING FOR ADAPTIVE VALUE AND COSTS

Abstract Plants shaded by neighbors or overhead foliage experience both a reduction in the ratio of red to far red light (R:FR), a specific cue perceived by phytochrome, and reduced photosynthetically active radiation (PAR), an essential resource. We tested the adaptive value of plasticity to crowding and to the cue and resource components of foliage shade in the annual plant Arabidopsis thaliana by exposing 36 inbred families from four natural populations to four experimental treatments: (1) high density, full sun; (2) low density, full sun; (3) low density, neutral shade; and (4) low density, low R:FR-simulated foliage shade. Genotypic selection analysis within each treatment revealed strong environmental differences in selection on plastic life-history traits. We used specific contrasts to measure plasticity to density and foliage shade, to partition responses to foliage shade into phytochrome-mediated responses to the R:FR cue and responses to PAR, and to test whether plasticity was adaptive (i.e., in the same direction as selection in each environment). Contrary to expectation, we found no evidence for adaptive plasticity to density. However, we observed both adaptive and maladaptive responses to foliage shade. In general, phytochrome-mediated plasticity to the R:FR cue of foliage shade was adaptive and counteracted maladaptive growth responses to reduced PAR. These results support the prediction that active developmental responses to environmental cues are more likely to be adaptive than are passive resource-mediated responses. Multiple regression analysis detected a few costs of adaptive plasticity and adaptive homeostasis, but such costs were infrequent and their expression depended on the environment. Thus, costs of plasticity may occasionally constrain the evolution of adaptive responses to foliage shade in Arabidopsis, but this constraint may differ among environments and is far from ubiquitous. Editor: D. Roff
Effects of Several Applications of Digested Sewage Sludge on Soil and Plants

Abstract Sewage sludge production has significantly increased during the last years in European Union (EU) countries, being primarily used for agricultural purposes. In this study, digested sewage sludge was applied to greenhouse soil over a three-year period (2001–2003), with three sludge treatments in the first two years (2, 4, and 6 kg m−2) and three more applications using a greater quantity in the last year (6, 8, and 10 kg m−2). The effects of sewage sludge application on soil and on a leafy crop (Lactuca sativa L.) were studied. Mineral elements, organic matter, pH, and heavy metals were measured in soil and plant tissues. Pathogen and indicator microorganism dynamics in soil were also determined after each sludge application. Results showed that sewage sludge applications increased organic matter, P, and N Ca content in soil. Furthermore, Zn, Pb, Ni, and Cu content increased in soils, primarily after high doses of sludge. The highest yield value was obtained in the second-year harvest, since the last sludge application did not increase yield. Fecal coliform numbers decreased significantly one month after sludge application. However, total coliforms, Clostridium sulphite-reducers and Salmonella, were present in soils three months after sludge application.
Trimer Stabilization, Oligomerization, and Antibody-Mediated Cell Surface Immobilization Improve the Activity of Soluble Trimers of CD27L, CD40L, 41BBL, and Glucocorticoid-Induced TNF Receptor Ligand1

For many ligands of the TNF family, trimer stability and oligomerization status are crucial determinants of receptor activation. However, for the immunostimulatory ligands CD27L, CD40L, 41BBL, and glucocorticoid-induced TNF receptor ligand (GITRL) detailed information regarding these requirements is lacking. Here, we comprehensively evaluated the effect of trimer stability and oligomerization on receptor activation by these ligands. Treatment with soluble Flag-tagged CD27L, 41BBL, and GITRL minimally activated receptor signaling, while Flag-CD40L was highly active. Oligomerization with anti-Flag Abs further enhanced the specific activity of Flag-CD40L 10-fold and of Flag-41BBL more than 200-fold, but it failed to activate Flag-CD27L and Flag-GITRL. We next investigated the relevance of trimer stability by introducing the tenascin-C (TNC) trimerization domain, yielding stabilized Flag-TNC-ligand trimers. Oligomerization with anti-Flag Ab potently activated signaling by Flag-TNC-CD27L and Flag-TNC-GITRL and, albeit to a lesser extent, Flag-TNC-CD40L and Flag-TNC-41BBL. Forced hexamerization, by introducing an Ig Fc domain, revealed that hexameric derivatives of Flag-TNC-41BBL, Flag-CD40L, and Flag-TNC-GITRL all activate receptor signaling with high efficiency, whereas hexameric Flag-CD27L variant left inactive. Finally, we attempted to selectively activate receptor signaling on targeted cells, by using Ab fragment (single-chain fragment variable region, scFv)-ligand fusion proteins, an approach previously applied to other TNF ligands. Target cell surface Ag-selective activation was achieved for scFv-41BBL, scFv-CD40L, and scFv-GITRL, although the latter two displayed already significant activity toward Ag-negative cells. In conclusion, our data establish that trimeric CD40L is active, 41BBL requires hexamerization, GITRL requires trimer stabilization, and CD27L requires trimer stabilization and oligomerization. Furthermore, surface immobilization might be exploited to gain locally enhanced ligand activity.
Acute dextran sulfate sodium (DSS)‐induced colitis promotes gut microbial dysbiosis in mice

The most widely used and characterized experimental model of ulcerative colitis (UC) is the epithelial erosion, dextran sulfate sodium (DSS)‐induced colitis, which is developed by administration of DSS in drinking water. We investigated fecal and colonic mucosa microbial composition and functional changes in mice treated with DSS. C57Bl/6 mice received 5% DSS in drinking water for 5 days. Inflammation was evaluated clinically and by analysis of colonic tissue cytokine levels and C‐reactive protein (CRP) in the serum. Colonic mucosa and fecal samples were used for DNA extraction and the V4 region of bacterial 16S rRNA gene was subjected to MiSeq Illumina sequencing. Alpha‐ and beta‐diversities, and compositional differences at phylum and genus levels were determined, and bacterial functional pathways were predicted. DSS increased disease severity, serum CRP and cytokines IL‐1β and IL‐6, but decreased bacterial species richness, and shifted bacterial community composition. Bacteroides, Turicibacter, Escherichia, Clostridium, Enterobacteriaceae, Clostridiaceae, Bacteroidaceae, Bacteroidales, among other taxa were associated with DSS treatment in fecal and colonic samples. Also, DSS altered microbial functional pathways in both colonic mucosa and fecal samples. Conclusions: The development of colitis in DSS model was accompanied with reduced microbial diversity and dysbiosis of gut microbiota at lower taxonomical levels.
Activity of Retapamulin against Streptococcus pyogenes and Staphylococcus aureus Evaluated by Agar Dilution, Microdilution, E-Test, and Disk Diffusion Methodologies

ABSTRACT The in vitro activity of retapamulin against 106 Staphylococcus aureus isolates and 109 Streptococcus pyogenes isolates was evaluated by the agar dilution, broth microdilution, E-test, and disk diffusion methodologies. Where possible, the tests were performed by using the CLSI methodology. The results of agar dilution, broth microdilution, and E-test (all with incubation in ambient air) for S. aureus yielded similar MICs, in the range of 0.03 to 0.25 μg/ml. These values corresponded to zone diameters between 25 and 33 mm by the use of a 2-μg retapamulin disk. Overall, 99% of the agar dilution results and 95% of E-test results for S. aureus were within ±1 dilution of the microdilution results. For S. pyogenes, the MICs obtained by the agar and broth microdilution methods (both after incubation in ambient air) were in the range of 0.008 to 0.03 μg/ml, and E-test MICs (with incubation in ambient air) were 0.016 to 0.06 μg/ml. For S. pyogenes, 100% of the agar dilution MIC results were within ±1 dilution of the broth microdilution results. E-test MICs (after incubation in ambient air) were within ±1 and ±2 dilutions of the broth microdilution results for 76% and 99% of the isolates, respectively. E-test MICs for S. pyogenes strains in CO2 were up to 4 dilutions higher than those in ambient air. Therefore, it is recommended that when retapamulin MICs are determined by E-test, incubation be done in ambient air and not in CO2, due to the adverse effect of CO2 on the activity of this compound. Diffusion zones (with incubation in CO2) for S. pyogenes were 18 to 24 mm. Retapamulin MICs for all strains by all methods (with incubation in ambient air) were ≤0.25 μg/ml. These results demonstrate that S. pyogenes (including macrolide-resistant strains) and S. aureus (including methicillin-resistant and vancomycin-nonsusceptible strains) are inhibited by very low concentrations of retapamulin and that all four testing methods are satisfactory for use for susceptibility testing.
Prevalence and Geographic Distribution Pattern of Asthma in Tehran by ECRHS

Background: Asthma, involving 5–10% of global population, has a heterogeneous distribution in the community regardless of age and its prevalence and incidence tend to grow worldwide as reported by many recent epidemiologic surveys. Materials and Methods: The present study aimed to survey the prevalence of asthma symptoms in Tehran as the first attempt in terms of situation analysis of the disease in the Iranian society by using relevant parts of the European Community Respiratory Health Survey (ECRHS) questionnaire. Results: Wheezing was reported in 48% of males and 34% of females in the age range of 20–44 years, around 50% of which was associated with breathlessness or cold. , the people who answered “yes” to the questions 1 (wheezing), 4 (coughing), 5 (asthma history) or 7 (nasal allergy) were totally 211 among whom 124 (58.8%) were males and the rest (41.2%) were females. Conclusion: Asthma symptoms decrease the quality of life and impose high costs on the healthcare system in many countries. A low rate of participants had been informed about their asthma by physicians and not all of them were taking medications. Risk factor analysis and control is strongly advised in order to lessen the prevalence of the disease and symptoms. Air pollution, smoking, unhealthy life style and many personal and social factors need to be assessed and eliminated. It seems that a- second phase- ECRH survey should be conducted to assess the situation of asthma through population of Tehran.
Flexible Funding as a Promising Strategy to Prevent Homelessness for Survivors of Intimate Partner Violence

The complex interrelationship between intimate partner violence (IPV) victimization and housing instability has been well established. Being the victim of IPV is a leading cause of homelessness for women, and once someone is homeless, their lives often spiral downward quickly. While some IPV survivors require extensive and possibly long-term assistance to achieve safe and stable housing (especially if they are contending with multiple complex issues), others could avoid homelessness if provided with immediate, individualized, and flexible assistance. For these survivors, whose housing has been otherwise stable but who face homelessness because of a crisis related to IPV, a brief intervention that includes flexible funding can restore a family’s equilibrium and prevent the devastating repercussions associated with homelessness. A longitudinal evaluation of a flexible funding program in Washington, D.C., found that this brief, relatively inexpensive intervention may increase housing stability—94% of clients were housed 6 months after funding was received. Implications for both research and practice are discussed.
A PBP2x from a Clinical Isolate of Streptococcus pneumoniae Exhibits an Alternative Mechanism for Reduction of Susceptibility to β-Lactam Antibiotics*

The human pathogen Streptococcus pneumoniae is one of the main causative agents of respiratory tract infections. At present, clinical isolates of S. pneumoniae often exhibit decreased susceptibility toward β-lactams, a phenomenon linked to multiple mutations within the penicillin-binding proteins (PBPs). PBP2x, one of the six PBPs of S. pneumoniae, is the first target to be modified under antibiotic pressure. By comparing 89 S. pneumoniae PBP2x sequences from clinical and public data bases, we have identified one major group of sequences from drug-sensitive strains as well as two distinct groups from drug-resistant strains. The first group includes proteins that display high similarity to PBP2x from the well characterized resistant strain Sp328. The second group includes sequences in which a signature mutation, Q552E, is found adjacent to the third catalytic motif. In this work, a PBP2x from a representative strain from the latter group (S. pneumoniae 5259) was biochemically and structurally characterized. Phenotypical analyses of transformed pneumococci show that the Q552E substitution is responsible for most of the reduction of strain susceptibility toward β-lactams. The crystal structure of 5259-PBP2x reveals a change in polarity and charge distribution around the active site cavity, as well as rearrangement of strand β3, emulating structural changes observed for other PBPs that confer drug resistance to Gram-positive pathogens. Interestingly, the active site of 5259-PBP2x is in closed conformation, whereas that of Sp328-PBP2x is open. Consequently, S. pneumoniae has evolved to employ the same protein in two distinct mechanisms of antibiotic resistance.
Influence of skewed and segmented magnet rotor on IPM machine performance and ripple torque for electric traction

The paper presents impacts of the stator slot with skew and segment magnet rotor on the performance of interior permanent magnet (IPM) machine for an electric traction. Comparisons of the average torque, torque ripples, cogging torque and no-load back EMF with skew and un-skew are given and how suitable a segmented rotor IPM machine and its torque characteristic and the field weakening capability are investigated. The results of the machine performance comparisons are based on comprehensive use of finite element analysis tools (Ansoft Maxwell 2D). One of the machine designs with one stator slot-pitch skew and no-segment magnet rotor for electric traction has been manufactured as prototype. From the FEA results, it shows that the IPM synchronous machine with two-teeth stator slots skewed and two-segmented magnet rotor has better performance than the conventional IPM synchronous machine.
Plasma virion reverse transcriptase activity and heat dissociation-boosted p24 assay for HIV load in Burkina Faso, West Africa

Background:In resource-limited settings, the requirement for inexpensive, easy-to-perform viral load monitoring has increased with greater antiretroviral drug availability. Objectives:To evaluate feasibility, in Burkina Faso, of a simple assay for plasma HIV reverse transcriptase (RT) activity quantification compared to heat dissociation-boosted (HDB) p24 antigen and RNA-based quantifications in plasma samples from HIV-infected patients. Methods:Plasma viraemia was quantified by RT activity, HDB-p24 and RNA copies in 84 samples from 70 HIV-1 group M-infected patients (82% non-B subtype, 93% treatment naive), including serial samples from nine patients. Results:RT activity detected 86% of plasma samples containing measurable RNA copies; corresponding to 0, 93 and 100% of samples with 1.7–4.0 log10, 4.1–4.8 log10 and 4.9–6.7 log10 RNA copies/ml, respectively. HDB-p24 detected 77% of plasma samples containing measurable RNA copies; corresponding to 27, 80 and 86% of samples with 1.7–4.0 log10, 4.1–4.8 log10 and 4.9–6.7 log10 RNA copies/ml, respectively. Measurement error based on one-way analysis of variance between RT activity and HDB-p24 values with RNA copies showed good agreement with RT activity (ME, <10%), however poorer agreement was obtained with HDB-p24 values (ME, >10%). Patient follow up showed a similar pattern of viraemia with RNA and RT activity assays. Conclusion:Field trials in Burkina Faso support the practical use of plasma RT activity assay as an affordable alternative for HIV viral load determination in regions where RNA detection remains difficult to perform. HDB-p24 use requires further evaluation before being considered as an alternative method in African HIV-infected patient follow up.
Strenuous exercise-induced change in redox state of human serum albumin during intensive kendo training.

A high-performance liquid chromatographic (HPLC) analysis of human serum albumin (HSA) using an ion-exchange (DEAE-form) column shows three components: The principal component corresponds to human mercaptalbumin (HMA); the secondary to nonmercaptalbumin (HNA), having mixed disulfide with cystine (HNA[Cys]), or oxidized glutathione (HNA[Glut]); and the tertiary to HNA, oxidized more highly than mixed disulfide. The purpose of the present study is to clarify the effects of strenuous exercise load on HMA--><--HNA conversion (i.e., dynamic change in redox state) of HSA from elite kendo athletes (n=30; 20.0+/-1.1 years old). They participated in an intensive kendo training camp for 5 d. The mean value for the HMA fraction (f[HMA]) of kendo athletes after camp (62.8+/-2.4%) was significantly lower than before camp (71.9+/-3.7%) (p<0.0005). In contrast, the mean value for f(HNA-1) (i.e., f[HNA(Cys) and HNA(Glut)]) after camp (34.2+/-2.1%) was significantly higher than before camp (25.7+/-3.7%) (p<0.0005). These results suggested that strenuous physical exercise markedly increased the oxidized albumin level in extracellular fluids during the intensive training camp.
Disruption of Ribosomal Scanning on the 5′-Untranslated Region, and Not Restriction of Translational Initiation per se, Modulates the Stability of Nonaberrant mRNAs in the Yeast Saccharomyces cerevisiae*

Translation and mRNA decay constitute key players in the post-transcriptional control of gene expression. We examine the mechanisms by which the 5′-untranslated region (UTR) of nonaberrant mRNAs acts to modulate both these processes in Saccharomyces cerevisiae Two classes of functional relationship between ribosome-5′-UTR interactions and mRNA decay are identifiable. In the first of these, elements in the main open reading frame (ORF) dictate how the decay process reacts to inhibitory structures in the 5′-UTR. The same types of stability modulation can be elicited by trans-regulation of translation via inducible binding of the iron-regulatory protein to an iron-responsive element located 9 nucleotides from the 5′ cap. A eukaryotic translational repressor can therefore modulate mRNA decay via the 5′-UTR. In contrast, translational regulation mediated via changes in the activity of the cap-binding eukaryotic translation initiation factor eIF-4E bypasses translation-dependent pathways of mRNA degradation. Thus modulation of mRNA stability via the 5′-UTR depends on disruption of the scanning process, rather than changes in translational initiation efficiency per se In the second class of pathway, an upstream ORF (uORF) functions as a powerful destabilizing element, inducing termination-dependent degradation that is apparently independent of any main ORF determinants but influenced by the efficiencies of ribosomal recognition of the uORF start and stop codons. This latter mechanism provides a regulatable means to modulate the stability of nonaberrant mRNAs via a UPF-dependent pathway.