Miracle-dz/UniFAR-FTUs huggingface dataset:
The SRY cantilever motif discriminates between sequence- and structure-specific DNA recognition: alanine mutagenesis of an HMG box.

The high-mobility-group (HMG) box defines a DNA-bending motif conserved among architectural transcription factors. A "hydrophobic wedge" at the protein surface provides a mechanism of DNA bending: disruption of base stacking by insertion of a sidechain "cantilever. " First described in the mammalian testis-determining factor SRY, the cantilever motif consists of adjacent aromatic and nonpolar sidechains at the crux of the HMG box (residues 12 and 13). Here, the role of these side chains in DNA recognition is investigated by alanine mutagenesis. F12A and I13A substitutions in the SRY HMG box each permit native folding and thermal stability (as monitored by circular dichroism and 1H-NMR) but eliminate sequence-specific DNA-binding activity (as detected by gel-mobility shift). On binding to the sharp angles of a four-way DNA junction (4WJ), however, the substitutions each promote formation of a high-molecular-weight aggregate, presumably by DNA-dependent oligomerization. The substitutions have opposite effects on initial binding to the 4WJ: whereas such binding is attenuated ten-fold by F12A, it is enhanced by I13A. A foreshortened "alanine cantilever", not observed among specific HMG boxes, occurs in a non-specific domain (HMG-1A) and may enhance architecture-selective DNA recognition.
Processing and Transport of Matrix γ-Carboxyglutamic Acid Protein and Bone Morphogenetic Protein-2 in Cultured Human Vascular Smooth Muscle Cells

Matrix γ-carboxyglutamic acid protein (MGP) is a member of the vitamin K-dependent protein family with unique structural and physical properties. MGP has been shown to be an inhibitor of arterial wall and cartilage calcification. One inhibitory mechanism is thought to be binding of bone morphogenetic protein-2. Binding has been shown to be dependent upon the vitamin K-dependent γ-carboxylation modification of MGP. Since MGP is an insoluble matrix protein, this work has focused on intracellular processing and transport of MGP to become an extracellular binding protein for bone morphogenetic protein-2. Human vascular smooth muscle cells (VSMCs) were infected with an adenovirus carrying the MGP construct, which produced non-γ-carboxylated MGP and fully γ-carboxylated MGP. Both forms of MGP were found in the cytosolic and microsomal fractions obtained from the cells by differential centrifugation. The crude microsomal fraction was shown to contain an additional, more acidic Ser-phosphorylated form of MGP believed to be the product of Golgi casein kinase. The data suggest that phosphorylation of MGP dictates different transport routes for MGP in VSMCs. A proteomic approach failed to identify a larger soluble precursor of MGP or an intracellular carrier protein for MGP. Evidence is presented for a receptor-mediated uptake mechanism for fetuin by cultured human VSMCs. Fetuin, shown by mass spectrometry not to contain MGP, was found to be recognized by anti-MGP antibodies. Fetuin uptake and secretion by proliferating and differentiating cells at sites of calcification in the arterial wall may represent an additional protective mechanism against arterial calcification.
Metabolic abnormalities associated with mild cognitive impairment in Parkinson disease

Objective: To use 18F-fluorodeoxyglucose (FDG) and PET to investigate changes in regional metabolism associated with mild cognitive impairment (MCI) in Parkinson disease (PD). Cognitive abnormalities are common in PD. However, little is known about the functional abnormalities that underlie the manifestations of MCI in this disorder. Methods: We used FDG PET to measure regional glucose metabolism in patients with PD with multiple-domain MCI (MD-MCI; n = 18), with single-domain MCI (SD-MCI; n = 15), and without MCI (N-MCI; n = 18). These patients were matched for age, education, disease duration, and motor disability. Maps of regional metabolism in the three groups were compared using statistical parametric mapping (SPM). We also computed the expression of a previously validated cognition-related spatial covariance pattern (PDCP) in the patient groups and in an age-matched healthy control cohort (n = 15). PDCP expression was compared across groups using analysis of variance. Results: SPM revealed decreased prefrontal and parietal metabolism (p < 0.001) in MD-MCI relative to N-MCI, as well as an increase in brainstem/cerebellar metabolism (p < 0.001) in this group. In these regions, SD-MCI occupied an intermediate position between the two other groups. PDCP expression was abnormally elevated in the N-, SD-, and MD-MCI groups (p < 0.05), increasing stepwise with worsening cognitive impairment (p < 0.01). Conclusions: Early cognitive decline in Parkinson disease as defined by mild cognitive impairment is associated with discrete regional changes and abnormal metabolic network activity. The quantification of these alterations with 18F-fluorodeoxyglucose PET may allow for the objective assessment of the progression and treatment of this disease manifestation. GLOSSARY: BA = Brodmann area; BNT = Boston Naming Test; CVLT = California Verbal Learning Test; FDG = 18F-fluorodeoxyglucose; FWHM = full width at half maximum; HVOT = Hooper Visual Organization Test; MCI = mild cognitive impairment; MD-MCI = multiple domain MCI; MMSE = Mini-Mental State Examination; PD = Parkinson disease; PDCP = PD-related cognitive pattern; SD-MCI = single domain MCI; SDMT = Symbol Digit Modality Test; SPM = statistical parametric mapping; UPDRS = Unified Parkinson's Disease Rating Scale; VOI = volume of interest; WCST = Wisconsin Card Sorting Test.
Epidemiology of vertebral osteomyelitis (VO) in France: analysis of hospital-discharge data 2002–2003

SUMMARY Vertebral osteomyelitis (VO) is a rare event. To estimate the incidence of VO in France for 2002–2003, national hospital-discharge data were used. Hospital stays were categorized as definite, probable or possible VO. Unique patient identification numbers allowed the investigators to link patients with multiple hospital stays and to analyse data for individual patients. A sample of medical records was reviewed to assess the specificity of the VO case definition. In 2002–2003, 1977 and 2036 hospital stays corresponding to 1422 and 1425 patients (median age 59 years, male:female ratio 1·5) were classified as definite (64%), probable (24%) and possible (12%) VO. The overall incidence of VO was 2·4/100 000. Incidence increased with age: 0·3/100 000 (<20 years), 3·5/100 000 (50–70 years) and 6·5/100 000 (>70 years). The main infectious agents reported were Staphylococcus spp. (38%) and Mycobacterium tuberculosis (31%). The most frequent comorbidities were septicaemia (27%) and endocarditis (9%). Three percent of patients died. A review of 90 medical records confirmed the diagnosis of VO in 94% of cases. Using a hospital database and a specific case definition, nationwide surveillance of VO is possible.
The Dbl-related Protein, Lfc, Localizes to Microtubules and Mediates the Activation of Rac Signaling Pathways in Cells*

The possibility that the Dbl family member Lfc can activate Rac1 in cells is investigated in this study. Previously, we demonstrated that both Lfc and Lsc, like their closest relative Lbc, can act catalytically in stimulating the guanine nucleotide exchange activity of RhoA in vitro. Neither Lfc nor Lsc stimulated the in vitro exchange activity of Cdc42 or Rac1; however, Lfc was capable of forming a tight complex with Rac1 in vitro. We show here that Lfc stimulates c-Jun kinase (JNK) activity in COS-7 cells. This stimulation was blocked by a dominant negative mutant of Rac1 and somewhat less effectively by dominant negative RhoA, but not by dominant negative Cdc42. Overexpression of Lfc in NIH 3T3 cells induced the formation of actin stress fibers and membrane ruffles, consistent with the activation of both RhoA and Rac1 signaling pathways, whereas overexpression of Lsc led exclusively to well developed stress fibers. Using a recently developed assay for measuring the cellular activation of Rac, we did not find that expression of Lfc increased the levels of GTP-bound Rac1. However, an examination of the cellular localization of Lfc showed that it was localized to microtubules, similar to what has been reported for activated Rac1, the mixed lineage kinase (MLK) and JNK. Moreover, we have found that the Pleckstrin homology (PH) domain of Lfc specifically associates with tubulin. Taken together, these findings suggest a model where the PH domain-mediated localization of Lfc to microtubules enables the recruitment of Rac to a site proximal to its signaling targets, resulting in JNK activation and actin cytoskeletal changes.
Understanding the Fluid Nature of Personhood – The Ring Theory of Personhood

Familial determination, replete with its frequent usurping of patient autonomy, propagation of collusion, and circumnavigation of direct patient involvement in their own care deliberations, continues to impact clinical practice in many Asian nations. Suggestions that underpinning this practice, in Confucian-inspired societies, is the adherence of the populace to the familial centric ideas of personhood espoused by Confucian ethics, provide a novel means of understanding and improving patient-centred care at the end of life. Clinical experience in Confucian-inspired Singapore, however, suggests that personhood is conceived in broader terms. This diverging view inspired a study of local conceptions of personhood and scrutiny of the influence of the family upon it. From the data gathered, a culturally appropriate, clinically relevant and ethically sensitive concept of personhood was proposed: the Ring Theory of Personhood (Ring Theory) that better captures the nuances of local conceptions of personhood. The Ring Theory highlights the fact that, far from being solely dependent upon familial centric ideals, local conceptions of personhood are dynamic, context dependent, evolving ideas delineated by four dimensions. Using the Ring Theory, the nature of familial influences upon the four dimensions of personhood - the Innate, Individual, Relational and Societal - are examined to reveal that, contrary to perceived knowledge, conceptions of personhood within Confucian societies are not the prime reason for the continued presence of this decision-making model but remain present within local thinking and practices as a sociocultural residue and primarily because of inertia in updating ideas.
The clock drawing test is a poor screen for very mild dementia

Objective To determine whether performance on the clock drawing test varies as a function of dementia severity and particularly whether it differentiates cognitively normal older adults from those with very mild dementia. Methods Clock drawings were obtained during the initial clinical assessments of 75 participants in a longitudinal study of healthy aging and dementia of the Alzheimer type (15 cognitively normal, 25 with very mild dementia, 21 with mild dementia, and 14 with moderate to severe dementia, as staged by the Clinical Dementia Rating). Each clock drawing later was judged blindly and independently by two raters according to six commonly used sets of scoring criteria. Results The same pattern of results was obtained for all six scoring methods. Inter-rater reliability was consistently high. Spearman correlations indicated that as dementia severity increased, clock drawing performance decreased. Analyses of variance revealed that although those with mild or moderate/severe dementia performed significantly worse on the clock drawing test than did individuals who had very mild dementia or who were cognitively normal, the latter two groups did not differ significantly. Sensitivity and specificity analyses revealed that all methods could distinguish between normal aging and dementia of at least mild severity. However, sensitivity for detecting very mild dementia was poor. Conclusion Although the clock drawing test can be scored reliably and can differentiate cognitively normal older adults from those with at least mild dementia of the Alzheimer type, it does not appear to be a useful screening instrument for detecting very mild dementia.
Neurotrophin-3 Levels in Cerebrospinal Fluid From Children With Bacterial Meningitis, Viral Meningitis, or Encephalitis

Neurotrophin-3 levels were measured in the cerebrospinal fluid of 35 patients with bacterial meningitis, viral meningitis, or encephalitis by two-site enzyme immunoassay. Elevated cerebrospinal fluid levels of neurotrophin-3 were demonstrated in 8 of 18 patients with bacterial meningitis. Follow-up examination of the eight patients at the convalescent stage showed diminished cerebrospinal fluid levels of neurotrophin-3. In contrast, none of the 17 patients with viral meningitis or encephalitis showed an elevation of neurotrophin-3 levels in cerebrospinal fluid. No relationships were observed between neurotrophin-3 levels and cerebrospinal fluid cell numbers, cerebrospinal fluid protein levels, serum C-reactive protein concentrations, or outcome in bacterial meningitis. Since neurotrophin-3 is involved in the survival of neurons and the modulation of the immune system, neurotrophin-3 could play a neuroprotective or immunomodulatory role in bacterial meningitis. (J Child Neurol 2000;15:19-21).
Revisiting mortality predictability of serum albumin in the dialysis population: time dependency, longitudinal changes and population-attributable fraction.

BACKGROUND Hypoalbuminaemia is a marker of malnutrition-inflammation complex syndrome (MICS) and a strong predictor of cardiovascular (CV) death in maintenance haemodialysis (MHD) patients. However, serum albumin may change over time. Hence, its time-varying associations with outcome may be different. METHODS Associations between 3-month averaged serum albumin levels, measured in a single laboratory using bromocresol green, and CV mortality were studied longitudinally in a 2-year cohort of 58,058 MHD patients. Mortality predictability of fixed baseline and trimonthly-varying serum albumin concentrations were compared. RESULTS Hazard ratios (HRs) of CV death strictly increased across decrements of baseline serum albumin, whereas the HR for time-varying serum albumin decrements below 3.8 g/dl did not differ. A drop in serum albumin in the first 6 months was associated with increasing all-cause and CV death risks in the subsequent 18 months, while a rise in serum albumin was a predictor of better survival independent of baseline serum albumin. The multivariate adjusted population-attributable fraction of death due to baseline serum albumin <3.8 g/dl was 19%. CONCLUSIONS Time-varying hypoalbuminaemia predicts all-cause and CV death differently from fixed measures of serum albumin in MHD patients. An increase in serum albumin over time is associated with better survival independent of baseline serum albumin or other MICS surrogates. If this association is causal, an intervention that could increase serum albumin >3.8 g/dl might reduce the number of MHD deaths in the USA by approximately 10,000 annually. Nutritional interventions examining benefits of increasing serum albumin in MHD patients are urgently needed.
Centrifugation and addition of glycerol at 22 degres C instead of 4 degrees C improve post-thaw motility and fertility of stallion spermatozoa.

The aims of this study were to evaluate the effects of cooling rate to 4 degrees C and temperature at the time of centrifugation/glycerol-addition (freezing extender: INRA82 + 2% egg yolk + 2.5% glycerol) on postcentrifugation recovery rate, post-thaw motility and per-cycle fertility. When centrifugation/glycerol-addition was performed at 4 degrees C (14 ejaculates), a moderate cooling rate (37 degrees C to 4 degrees C in I h) resulted in higher post-thaw motility (45%) than when using a slow cooling rate (37 degrees C to 4 degrees C in 4 h) (39%; P<0.05). When centrifugation/glycerol-addition was performed at 22 degrees C (37 degrees C to 22 degrees C in 10 min) (10 ejaculates), post-thaw motility was lower when spermatozoa were frozen directly from 22 degrees C (23%) than when spermatozoa were cooled to 4 degrees C (22 degrees C to 4 degrees C in 1 h) before freezing (47%; P<0.0001). When centrifugation/glycerol-addition was performed at 22 degrees C (before cooling at a moderate rate), as opposed to 4 degrees C (after cooling at a moderate rate), a significant improvement of 1) recovery of spermatozoa after centrifugation (P<0,0001), 2) post-thaw motility of spermatozoa at thawing (40% vs 36% (n < or = 291 ejaculates/group), P<0.0001) and 3) per-cycle fertility (56% vs 42% (n > or = 190 cycles/group), P<0.01) was observed. In conclusion, centrifugation/glycerol-addition at 22 degrees C followed by cooling to 4 degrees C at a moderate rate results in an improvement of post-thaw motility, spermatozoa recovery rate and per cycle fertility.
The Influence of Milling Time and  $\hbox{ZrB}_{2}$ Addition on the Superconducting Properties of  $\hbox{MgB}_{2}$

High-energy ball milling is generally used in granular materials to increase grain connectivity and densification. In this study, different high-energy ball milling times were investigated to optimize the MgB2 superconducting properties in samples with added ZrB2. The objectives of this addition were to modify the Mg planes and to create crystalline defects in the superconducting matrix that can act as pinning centers. We observed the behavior of the dopant on the superconducting properties, and found the optimal ball milling time of 300 min improved . ic in high magnetic field and Hirr from 7.2 to 10.0 T at 4.2 K.
Relative contribution of psychosocial variables to the explanation of physical activity in three population-based adult samples.

BACKGROUND Despite large differences in physical activity by demographic subgroup, few studies have identified correlates for specific age and sex groups. The present study quantified the unique variance accounted for in each subgroup by the main psychosocial variables. METHODS Three random samples, ages 16-25, 35-45, and 50-65, with a total of 2,390 Belgian subjects, completed psychosocial questionnaires and were interviewed at home. RESULTS Social influences, self-efficacy, perceived benefits, and perceived barriers varied in importance by age and sex groups. Social variables provided the most unique information about physical activity for all age and sex groups, except older females. Competition was a significant perceived benefit only for young men, whereas health was the most significant perceived benefit for young women. Among older women and men, health concerns were significant perceived barriers to participation in physical activity. CONCLUSIONS The present results provide hypotheses about mediators of physical activity that can be applied in interventions tailored to the needs of various subgroups.
Functionality of Selected Aromatic Lamiaceae in Attracting Pollinators in Central Spain

Abstract Planting floral margins in agricultural landscapes has been shown to increase the abundance of pollinators in agro-ecosystems. However, to create efficient margins, it is necessary to use attractive, not weedy native plants with different blooming periods to prolong the availability of floral resources. Six native perennial plants of the Lamiaceae with different blooming periods were studied in a randomized block design, with the final aim to select the most efficient plants in floral mixtures by studying relationships between their floral phenology, floral density, and attractiveness to pollinators in Central Spain. In addition, their spatial expansion, i.e., potential weediness, was estimated under the field conditions, as the final purpose of the plants is to be implemented within the agro-ecosystems. The results showed that plant species with higher floral density (Nepeta tuberosa L. and Hyssopus officinalis L.) showed significantly higher attractiveness to pollinators and enhanced the attractiveness of floral mixtures. Species that bloomed in early spring (Salvia verbenaca L.) and in summer (Melissa officinalis L. and Thymbra capitata L.) did not efficiently contribute to the attractiveness of the mixtures to pollinators. In addition, besides high floral density of Salvia officinalis L. and N. tuberosa in the spring, warm and dry weather in spring 2012 enhanced the activity of bees, while cold and rainy weather in spring 2013 enhanced the activity of hoverflies. None of the plants showed weedy growth and so posed no danger of invading adjacent crops.
A prospective randomized trial of maintenance versus nonmaintenance intravesical bacillus Calmette-Guérin therapy of superficial bladder cancer.

Between August 1981 and July 1984, 93 patients with polychronotopic superficial papillary carcinoma (Ta and/or T1), flat carcinoma in situ (Tis), or concomitant superficial papillary and in situ bladder carcinoma were entered into a prospective randomized trial of maintenance v nonmaintenance intravesical bacillus Calmette-Guérin (BCG) therapy. Forty-six patients who received BCG weekly for 6 weeks were compared with 47 patients receiving the six-weekly doses of BCG plus monthly BCG for 2 years. Both groups were evaluated every 3 months by cytology, cystoscopy, and biopsy. A significant reduction in the number of recurrent tumors per patient-month was demonstrated for both groups (P less than .0001); however, the difference in reduction of tumors between the two groups was not significant. Additionally, patients receiving maintenance and nonmaintenance therapy had similar tumor recurrence and progression rates. These results indicate that monthly maintenance BCG does not prevent, delay, or reduce tumor recurrence or progression observed with the 6-week regimen. Maintenance BCG was associated with increased local toxicity, primarily dysuria, frequency, and urgency. Dosage reduction was required in 22 of 47 patients (46.8%). When the data were subjected to multivariate analysis, the presence or absence of tumor following induction BCG and PPD skin test results were found to be significant variables. Controlling for either the presence or absence of tumor following induction BCG, tumor recurrence and progression rates were not significantly different for the two treatment groups. However, the absence of tumor after induction BCG was associated with a longer disease-free duration (P = .00001) and time to progression (P = .095). Patients with a reactive tuberculin skin test before and after induction BCG had significantly less tumor recurrences than patients with different PPD skin tests results (P = .02). Tumor progression was not related to tuberculin skin testing.