Miracle-dz/UniFAR-FTUs huggingface dataset:
An iron‐sulfur center essential for transcriptional activation by the redox‐sensing SoxR protein.

The soxRS oxidative stress regulon of Escherichia coli is triggered by superoxide (O2.‐) generating agents or by nitric oxide through two consecutive steps of gene activation. SoxR protein has been proposed as the redox sensing gene activator that triggers this cascade of gene expression. We have now characterized two forms of SoxR: Fe‐SoxR contained non‐heme iron (up to 1.6 atoms per monomer); apo‐SoxR was devoid of Fe or other metals. The spectroscopic properties of Fe‐SoxR indicated that it contains a redox active iron‐sulfur (FeS) cluster that is oxidized upon extraction from E. coli. Fe‐SoxR and apo‐SoxR bound the in vivo target, the soxS promoter, with equal affinities and protected the same region from DNase I in vitro. However, only Fe‐SoxR stimulated transcription initiation at soxS in vitro > 100‐fold, similar to the activation of soxS expression in vivo. This stimulation occurred at a step after the binding of RNAP and indicates a conformational effect of oxidized Fe‐SoxR on the soxS promoter. The variable redox state of the SoxR FeS cluster may thus be employed in vivo to modulate the transcriptional activity of this protein in response to specific types of oxidative stress.
On the natural course of oral lichen lesions in a Swedish population-based sample.

OBJECTIVES The aim was to assess the natural course of oral lichen lesions (OLL) among unselected, non-consulting individuals. SUBJECTS AND METHODS A cohort of 327 subjects with OLL, confirmed in 1973-1974 during a population-based survey in two Swedish municipalities, was followed through January 2002 via record linkages with nationwide and essentially complete registers. A sample of 80 drawn from the 194 surviving subjects who still resided in the area in 1993-1995 was invited for interview and oral re-examination. RESULTS At the end of follow-up, one case of oral cancer was detected, while 0.4 were expected. The overall mortality among subjects with OLL was not significantly different from that in the 15,817 OLL-free subjects who participated in the initial population based survey in 1973-1974. The lesion had disappeared in 14 (39%) of 36 re-examined subjects with white OLLs in 1973-1974, and four (11%) had transformed into red types. In the corresponding group of 19 with red forms initially, five (26%) had become lesion free and four (21%) had switched to white types. Although the cohort size does not permit firm conclusions regarding oral cancer risk, the natural course over up to 30 years appears to be benign in the great majority.
Applications of mass spectrometry in drug metabolism: 50 years of progress*

Abstract Mass spectrometry plays a pivotal role in drug metabolism studies, which are an integral part of drug discovery and development nowadays. Metabolite identification has become critical to understanding the metabolic fate of drug candidates and to aid lead optimization with improved metabolic stability, toxicology and efficacy profiles. Ever since the introduction of atmospheric ionization techniques in the early 1990s, liquid chromatography coupled with mass spectrometry (LC/MS) has secured a central role as the predominant analytical platform for metabolite identification as LC and MS technologies continually advanced. In this review, we discuss the evolution of both MS technology and its applications over the past 50 years to meet the increasing demand of drug metabolism studies. These advances include ionization sources, mass analyzers, a wide range of MS acquisition strategies and data mining tools that have substantially accelerated the metabolite identification process and changed the overall drug metabolism landscape. Exemplary applications for characterization and identification of both small-molecule xenobiotics and biological macromolecules are described. In addition, this review discusses novel MS technologies and applications, including xenobiotic metabolomics that hold additional promise for advancing drug metabolism research, and offers thoughts on remaining challenges in studying the metabolism and disposition of drugs and other xenobiotics.
Clinical Evaluation of a Peritoneal Dialysis Solution with 33 mmol/L Bicarbonate

Objective To evaluate the efficacy and safety of a new peritoneal dialysis solution with 33 mmol/L bicarbonate. Design In an acute, prospective, randomized crossover study, 8 patients were randomized in two groups of 4. On the first study day, the first group performed two consecutive 4-hour exchanges with a dialysis solution containing 35 mmol/L lactate: the first exchange with 13.6 g/L and the second with 38.6 g/L dextrose. On the second study day, the same type of exchanges were performed with bicarbonate. The second group underwent the same treatment, but used bicarbonate solutions on the first day and control solutions on the second study day. Thirty-three patients participated in a 2-month prospective and randomized study. After a 4-week baseline period using solutions containing 40 mmol/L lactate, the patients were dialyzed with either 33 mmol/L bicarbonate solutions or 40 mmol/L lactate solutions. Setting Peritoneal dialysis units at the University Hospital of Brescia and the Niguarda Hospital of Milan, Italy. Results Acute study: Control and bicarbonate solutions had similar effects on blood chemistries and peritoneal transport. Chronic study: Mean venous bicarbonate concentrations remained unchanged in the control group (26.6 -27.2 mmol/L), but decreased significantly in the bicarbonate group from 28.8 mmol/L at the start of the study to 23.0 mmol/L after 2 months of bicarbonate administration. Other biochemical parameters remained unchanged. Conclusion A peritoneal dialysis solution with a bicarbonate level of 33 mmol/L does not adequately correct uremic acidosis.
Role of the Posterolateral Cerebellum in Language

Abstract: Historically, scientists have believed that the cerebellum controls only movement. However, recent evidence from neuroimaging and human lesion studies suggests that the right posterolateral cerebellar hemisphere is involved, independently of movement, in helping an individual to generate verbs for given nouns. We sought to elucidate the key factors contributing to the verb generation deficits of subjects with right posterolateral cerebellar damage and thus to better understand the specific contributions of the postero‐lateral cerebellum to language. We compared the performance of subjects with focal left‐sided posterolateral cerebellar lesions, those with focal right‐sided posterolateral cerebellar lesions, and neurologically normal pilot control subjects on an antonym generation task, noun (category member) generation task, verb selection task, and lexical decision task. Preliminary results show that subjects with right cerebellar lesions are impaired relative to other subjects only on the antonym generation task. The results provide evidence that the right cerebellar language deficit is not due solely to deficits in “mental movement” coupled to a verb and that internal generation of a word seems to be a key factor in eliciting a deficit. In addition, a semantic processing demand may be necessary but insufficient to elicit a right cerebellar language deficit. The results support the theory that the right posterolateral cerebellar hemisphere assists the left cerebral hemisphere in helping an individual learn to generate specific types of spoken, two‐word associations. The full nature of this process awaits further investigation.
Immunoexpression of Ezrin and CD44 in Patients With Osteosarcoma

Background Metastasis is an important prognostic factor among patients with osteosarcoma. It has been reported that ezrin is important in enabling metastasis and that CD44 expression leads to functional increases in ezrin activation. Objective The aim of this study was to correlate ezrin and CD44 expression with prognosis. Samples and Methods Patients with a diagnosis of osteosarcoma who had been treated at Hospital de Cancer de Barretos, Barretos, SP, Brazil, between 2000 and 2005 were selected from the Hospital Tumor Registry. Fifty-two patients and, among these, 34 surgical biopsy specimens of osteosarcoma before chemotherapy were reviewed by the Pathology Department. Ezrin and CD44H protein expression was evaluated using immunohistochemistry on the initial biopsy for these 34 samples. Results Most patients (76%) were ezrin-positive in cytoplasm and membrane (38.2%); 58.9% presented high-intensity staining and 50.0% had high scores. Half of the patients were CD44H-positive, predominantly in cytoplasm (38.2%); 20.6% presented staining in more than 50% of the cells. None of the markers showed associations with any of the clinicopathologic variables studied. Among the ezrin-positive patients, the 5-year survival rate was 12.8%, whereas it was 41.7% among ezrin-negative patients (P=0.121). The interaction between ezrin and poor histologic response among nonmetastatic patients showed an association with relapse-free 5-year survival of 100% versus 12.7% (P=0.042). The overall survival rates for CD44-positive and negative patients were similar (21.5% and 25.3%, respectively) (P=0.676). Conclusions Neither CD44H nor ezrin immunoexpression could predict the prognosis for patients with osteosarcoma in our small sample.
Early outcome after intravenous thrombolysis in patients with acute ischemic stroke.

BACKGROUND Patients with acute ischemic stroke who had early neurological improvement had better functional outcome. The purpose of this study was to determine factors associated with early clinical improvement and early worsening in patients with acute ischemic stroke treated with intravenous thrombolysis. PATIENTS AND METHODS Patients treated with intravenous recombinant tissue plasminogen activator (rtPA) between August 2008 and November 2010 were the subjects of this study. Early improvement was defined by marked, clinical improvement or complete recovery at 24 h (National Institutes of Health Stroke Scale (NIHSS) 0-4 at 24 h). Early worsening was defined by an increase in NIHSS ≥1 from baseline. The baseline characteristics were compared between patients with and without outcome of interest. RESULTS Of the 203 patients studied, 19 (9.4%) patients had complete recovery and 68 (33.5%) patients had marked clinical improvement (NIHSS 1-4) at 24 h. Most patients with early clinical improvement (86%) had favorable outcome at three months. Of the 22 (10.8%) patients who had early clinical worsening, only three (14%) patients achieved favorable outcome at three months and six (29%) patients died. Multivariate analysis revealed that older age (≥70 years old) (odd ratio (OR) 0.498, P = 0.049), severe stroke (NIHSS ≥15) (OR 0.154, P < 0.0001) and having intracerebral hemorrhage (ICH) (OR 0.364, P = 0.032) were inversely associated with early improvement. History of transient ischemic attack (TIA) (OR 7.724, P = 0.043) and ICH (OR 4.477, P = 0.008) were related to early worsening. CONCLUSIONS The presence of early clinical improvement or worsening within 24 h after treatment with rtPA had major impact on the outcome at three months.
Thalamic deep brain stimulation for the treatment of tremor due to multiple sclerosis: a prospective study of tremor and quality of life.

OBJECT In several studies a significant reduction in tremor after thalamic deep brain stimulation (DBS) has been reported among patients with multiple sclerosis (MS). It has not been determined if this results in an improved quality of life. In this study the authors prospectively evaluated the effects of thalamic DBS on tremor and quality of life. METHODS Videotapes of the patients' tremor were made preoperatively and 2 and 12 months postoperatively, and tremor was scored by a neurologist blinded to the treatment. Patients were tested pre- and postoperatively to measure any changes in their reported ability to perform selected activities of daily living and in their health-related quality of life. Patients were asked to complete a questionnaire about their satisfaction with the surgery. Postoperative changes were examined using paired t-tests. There were significant reductions in postural, action, and overall tremor at 2 and 12 months postoperatively. The patients' reported ability to feed themselves was significantly improved 2 months after surgery (p = 0.01). There were short-term trends toward improvement in reported dressing ability, personal hygiene, and writing. There were no significant changes in the SF-36 subscales or total score. CONCLUSIONS In this cohort of patients with MS who suffered from tremor, thalamic DBS significantly improved their tremor and ability to feed themselves. Patient satisfaction with the procedure, however, was variable. Preoperative patient education about what functions might (and might not) be improved is crucial to avoid unrealistic expectations. Our results indicate that younger patients with MS tremor who had a shorter disease duration and no superimposed ataxia benefited most from this surgery.
Epidemiology of traumatic dental injuries--a 12 year review of the literature.

BACKGROUND/AIM A traumatic dental injury (TDI) is a public dental health problem because of its frequency, occurrence at a young age, costs and that treatment may continue for the rest of the patient's life. The aim of this paper is to present a12-year, international review of the prevalence and incidence of TDIs including some background factors and a quick, easy method in registering TDIs to receive a primary understanding of the extent and severity of dental trauma. MATERIAL AND METHOD The databases of Medline, Cochrane, SSCI, SCI and CINAHL from 1995 to the present were used. RESULT The results indicate a high prevalence of TDIs in primary and permanent teeth and that TDIs exists throughout the world. The prevalence show that one third of all preschool children have suffered a TDI involving the primary dentition, one fourth of all school children and almost one third of adults have suffered a trauma to the permanent dentition, but variations exist both between and within countries. Activities of a person and the environment are probably more determining factors of TDIs than gender and age. A risk profile why some patients sustain multiple dental trauma episodes (MDTE) is necessary to present. All dental clinics should have a prospective ongoing registration of TDIs. The NUC method (N = no TDI, U = uncomplicated TDI, C = complicated TDI) presents if there has been any TDI and the severity of that trauma. CONCLUSION The trend of TDIs seems to be stable on a high level with variations largely reflecting local differences. Because of the complexity of TDIs, every dental clinic should have a prospective ongoing registration of number and severity of TDIs.
Cerebral activation during unilateral clenching in patients with temporomandibular joint synovitis and biting pain: an functional magnetic resonance imaging study.

BACKGROUND Functional magnetic resonance is a non-invasive method that can examine brain activity and has been widely used in various fields including jaw movement and pain processing. Temporomandibular disorder (TMD) is one of the most frequent facial pain problems. The objective of this study was to investigate the brain activities using functional magnetic resonance imaging (fMRI) during unilateral maximal voluntary clenching tasks in the TMD synovitis patients with biting pain. METHODS Fourteen TMD synovitis patients with unilateral biting pain and 14 controls were included in the study. Contralateral biting pain was defined as right molar clenching causing left temporomandibular joint (TMJ) pain. Ipsilateral biting pain was defined as right molar clenching causing right TMJ pain. Symptom Check List-90 (SCL-90) was administered to the patients and controls. Independent sample t-test was used to compare the SCL-90 subscales between the two groups. Unilateral clenching tasks were performed by the patients and controls. Imaging data were analyzed using SPM99. RESULTS Patients were divided into contralateral TMD biting pain group (n = 8) and ipsilateral TMD biting pain group (n = 6). The SCL-90 subscales were significantly different between the two groups for somatization, depression, anxiety, phobic anxiety, and paranoid ideation. Group analysis of the controls demonstrated brain activations in the inferior frontal gyrus, precentral gyrus, middle frontal gyrus, superior temporal gyrus, and insular. The areas of activation were different between right and left clenching task. In TMJ synovitis patients with contralateral or ipsilateral biting pain, the group analysis showed activations in the inferior frontal gyrus, superior temporal gyrus, medium frontal gyrus, precentral gyrus, and anterior cingulate cortex. CONCLUSIONS The inferior frontal gyrus and precentral gyrus play essential roles during the unilateral clenching task. Activation of anterior cingulate cortex in the synovitis patients with biting pain was associated with higher levels of psychological distress.
Mg2+ ions do not induce expansion of the melted DNA region in the open complex formed by Escherichia coli RNA polymerase at a cognate synthetic Pa promoter. A quantitative KMnO4 footprinting study.

Footprinting studies of prokaryotic open transcription complexes (RPO), based on oxidation of pyrimidine residues by KMnO4 and/or OsO4 at a single oxidant dose, have suggested that the extent of DNA melting in the transcription bubble region increases in the presence of Mg . In this work, quantitative KMnO4 footprinting in function of the oxidant dose of RPO, using Escherichia coli RNA polymerase (E(sigma)70) at a fully functional synthetic promoter Pa having -35 and -10 consensus hexamers, has been used to determine individual rate constants of oxidation of T residues in this region at 37degrees C in the absence of Mg2+ and in the presence of 10 mM MgCl2, and to evaluate therefrom the effect of Mg2+ on the extent of DNA melting. Population distributions of end-labeled DNA fragments corresponding to oxidized Ts were quantified and analyzed according to the single-hit kinetic model. Pseudo-first order reactivity rate constants, ki, thus obtained demonstrated that Mg2+ ions bound to RPO merely enhanced the reactivity of all 11 oxidizable thymines between the +3 and -11 promoter sites by a position-dependent factor: 3-4 for those located close to the transcription start point +1 in either DNA strand, and about 1.6 for those located more distantly therefrom. On the basis of these observations, we conclude that Mg2+ ions bound to RPO at Pa do not influence the length of the melted DNA region and propose that the higher reactivity of thymines results mainly from lower local repulsive electrostatic barriers to MnO4 diffusion around carboxylate binding sites in the catalytic center of RPO and promoter DNA phosphates.
Les effets de la démocratisation de l'enseignement en France : Une étude empirique

Cette these met en evidence l'impact de la massification de l'education des annees 80 sur le taux de rendement des etudes en France de 1983 a 2002. En outre, elle permet de faire le point sur l'avancee des techniques econometriques qui se sont developpees ces cinquante dernieres annees. Nous expliquons pourquoi il nous parait aujourd'hui essentiel de tenir compte, dans les diverses formalisations, des couts implicites et explicites qu'occasionne le choix de faire des etudes et de la probabilite de chomage qui differe selon les annees d'education. Le redoublement et la specificite du systeme educatif francais sont des elements qui amenent a penser que les « annees d'etudes » ne sont pas representatives du niveau des individus et que la variable explicative « diplome » convient davantage. En tenant compte de ces differents facteurs, le taux de rendement du baccalaureat a largement chute sur la periode pour etre desormais negatif autour de -1% alors que ceux des annees post-bac ont converge vers 10%, la licence demeurant toujours plus rentable que le master. D'autre part, le probleme du declassement du bac general s'accroit. L'utilisation d'enquetes plus riches en informations individuelles et relatives au passe familial montre qu'elles conditionnent aussi la reussite scolaire. La question de la poursuite ou de l'arret des etudes est soulevee. De nombreux eleves ont poursuivi leurs etudes alors qu'ils n'auraient, a priori, pas du continuer et vice versa. Les sensibilites et le gout des etudes ont un fort impact sur ce choix mais sont des variables qualitatives typiquement non mesurables qui echappent a l'econometrie.
Mandibular Condyle Lesions in Children with Juvenile Idiopathic Arthritis

Objective: To assess the prevalence of radiographically detectable destruction of the temporomandibular joints in children with juvenile idiopathic arthritis and to study the possible relationships between condylar destruction and type and duration of the disease, as well as the type of occlusion. Material And Method: The study group consisted of 66 children with juvenile idiopathic arthritis (27 boys, 39 girls; mean age, 11.9 years). The possible presence of condylar destruction was examined in panoramic radiographs. The medical history and the type of malocclusion were registered also. The statistical evaluation was performed by means of descriptive statistics, Student's t test, Pearson's chi-square, and an analysis of variance test. The whole procedure was repeated after a 4-week interval to estimate the error of the method. Results: Of the children with juvenile idiopathic arthritis, 50% showed some form of condylar destruction. Significant correlation was found between the type of the disease and the condyles affected. In the polyarticular type of juvenile idiopathic arthritis, 75% of the children presented affected condyles and 55.6% of them showed lesions bilaterally. The condylar affection was found to be independent of sex, although girls showed a tendency to bilateral lesions. In children with unilateral destruction, the right condyle was affected four times more frequently than the left. The duration of juvenile idiopathic arthritis seems to be significantly correlated to condylar destruction and especially to bilateral destruction. Conclusion: Children with juvenile idiopathic arthritis presented a remarkable prevalence of condylar destruction, which was correlated to the type and duration of the disease.
Degradation of the Amyloid β-Protein by the Novel Mitochondrial Peptidasome, PreP*♦

Recently we have identified the novel mitochondrial peptidase responsible for degrading presequences and other short unstructured peptides in mitochondria, the presequence peptidase, which we named PreP peptidasome. In the present study we have identified and characterized the human PreP homologue, hPreP, in brain mitochondria, and we show its capacity to degrade the amyloid β-protein (Aβ). PreP belongs to the pitrilysin oligopeptidase family M16C containing an inverted zinc-binding motif. We show that hPreP is localized to the mitochondrial matrix. In situ immuno-inactivation studies in human brain mitochondria using anti-hPreP antibodies showed complete inhibition of proteolytic activity against Aβ. We have cloned, overexpressed, and purified recombinant hPreP and its mutant with catalytic base Glu78 in the inverted zinc-binding motif replaced by Gln. In vitro studies using recombinant hPreP and liquid chromatography nanospray tandem mass spectrometry revealed novel cleavage specificities against Aβ-(1-42), Aβ-(1-40), and Aβ Arctic, a protein that causes increased protofibril formation an early onset familial variant of Alzheimer disease. In contrast to insulin degrading enzyme, which is a functional analogue of hPreP, hPreP does not degrade insulin but does degrade insulin B-chain. Molecular modeling of hPreP based on the crystal structure at 2.1 Å resolution of AtPreP allowed us to identify Cys90 and Cys527 that form disulfide bridges under oxidized conditions and might be involved in redox regulation of the enzyme. Degradation of the mitochondrial Aβ by hPreP may potentially be of importance in the pathology of Alzheimer disease.