Miracle-dz/UniFAR-FTUs huggingface dataset:
Etude des effets des rayonnements ionisants sur la niche hématopoïétique et traitement du syndrome aigu d'irradiation par thérapie génique chez le macaque irradié à forte dose

La niche des cellules souches hematopoietiques represente un compartiment complexe et radiosensible. Sa protection est necessaire pour la restauration de l'hematopoiese faisant suite a la myelosuppression due a l'exposition aux rayonnements ionisants. Nous avons dans un premier temps etudie l'effet des RI sur les progeniteurs endotheliaux et mesenchymateux de la niche par une etude de radiosensiblilite et une etude d'evaluation de la mort cellulaire. Nous avons propose par la suite une strategie innovante de therapie genique basee sur la secretion locale et a court terme du morphogene Sonic hedgehog visant a favoriser la reparation de niche vasculaire et de stimuler les cellules souches hematopoietiques et les cellules progenitrices residuelles. Nous avons etudie la reponse hematopoietique des singes irradies a 8-Gy gamma apres une seule injection intra-osseuse de cellules souches mesenchymateuses xenogeniques, multipotentes et d'origine adipocytaire transfectees avec un plasmide pIRES2-eGFP codant la proteine Shh. La duree de thrombocytopenie et celle de neutropenie ont ete significativement reduites chez les animaux greffes et les clonogenes sont normalises a partir du 42e jour. Les aires sous la courbe des numeration des plaquettes et des neutrophiles entre 0 et 30 jours ont ete significativement plus elevee chez les animaux traites que chez les temoins. La greffe d'explants de MatrigelTM colonises ou non avec des ASC chez des souris immunodeprimees a demontre une activite pro-angiogenique notable des ASC transfectees avec le plasmide Shh . Le suivi a long terme (180 a 300 jours) a confirme une reconstitution durable dans les quatre singes greffes. Globalement cette etude suggere que la greffe de cellules souches multipotentes Shh-peut representer une nouvelle strategie pour la prise en charge des dommages radio-induits de la niche.
Suppressive action of melatonin on the TH‐2 immune response in rats infected with Trypanosoma cruzi

Abstract: Control of the acute phase of Trypanosoma cruzi infection is critically dependent on cytokine‐mediated macrophage activation to intracellular killing, natural killer (NK) cells, CD4+ T cells, CD8+ T cells and B cells. Cell‐mediated immunity in T. cruzi infection is also modulated by cytokines, but in addition to parasite‐specific responses, autoimmunity can be also triggered. Importantly, cytokines may also play a role in the cell‐mediated immunity of infected subjects. Here we studied the role of cytokines in the regulation of innate and adaptive immunity during the acute phase of T. cruzi infection in Wistar rats. Melatonin is an effective regulator of the immune system. Macrophages and T lymphocytes, which have melatonin receptors, are target cells for the immunomodulatory function of melatonin. In this paper melatonin was orally given via two protocols: prior to and concomitant with infection. Both treatments were highly effective against T. cruzi with enhanced action for the concomitant treatment. The data suggest an up‐regulation of the TH‐1 immune response as all analyzed parameters, interleukin (IL)‐4, IL‐10, transforming growth factor‐β1 and splenocyte proliferation, displayed reduced levels as compared with the untreated counterparts. However, the direct effects of melatonin on immune cells have not been fully investigated during T. cruzi infection. We conclude that in light of the current results, melatonin exerted important therapeutic benefits through its immune regulatory effects.
An Examination of Two Coteaching Classrooms

The present study presents data on two classrooms that used a coteaching approach to provide services to students who were deaf, hard of hearing, and hearing. The author conducted extensive observations, as well as interviews with teachers, students, administrators, and parents. The resulting qualitative data supported coteaching's effectiveness as a service delivery model. However, the research also identified important and specific challenges. Seven subthemes about coteaching are presented, and quotes from various stakeholders are provided to support and illustrate the information reported. Suggestions for future research are provided. The author makes recommendations on how to establish coteaching teams and describes issues surrounding communication, staff development, and family involvement.
Lamina-Specific Synaptic Activation Causes Domain-Specific Alterations in Dendritic Immunostaining for MAP2 and CAM Kinase II

Polyribosomal complexes are selectively localized beneath postsynaptic sites on neuronal dendrites; this localization suggests that the translation of the mRNAs that are present in dendrites may be regulated by synaptic activity. The present study tests this hypothesis by evaluating whether synaptic activation alters the immunostaining pattern for two proteins whose mRNAs are present in dendrites: the dendrite-specific cytoskeletal protein MAP2 and the α-subunit of CAMKII. High-frequency stimulation of the perforant path projections to the dentate gyrus, which terminate in a discrete band on the dendrites of dentate granule cells, produced a two-stage alteration in immunostaining for MAP2 in the dendritic laminae. Five minutes of stimulation (30 trains) caused a decrease in MAP2 immunostaining in the lamina in which the activated synapses terminate. After more prolonged periods of stimulation (1–2 hr), there was an increase in immunostaining in the sideband laminae just proximal and distal to the activated band of synapses. The same stimulation paradigm produced a modest increase in immunostaining for α-CAMKII in the activated laminae, with no detectable changes in the sideband laminae. The alterations in immunostaining for MAP2 were diminished, but not eliminated, by inhibiting protein synthesis; the increases in CAMKII were not. These findings reveal that patterned synaptic activity can produce domain-specific alterations in the molecular composition of dendrites; these alterations may be caused in part by local protein synthesis and in part by other mechanisms.
Optimized release of recombinant proteins by ultrasonication of E. coli cells.

The release kinetics of beta-galactosidase protein have been determined during small-scale ultrasonication of E. coli cells. Among several studied parameters, ionic strength and cell concentration have the least influence on the rate of protein recovery, whereas sample volume and acoustic power dramatically affect the final yield of soluble protein in the cell-free fraction. The analysis of these critical parameters has prompted us to propose a simple model for E. coli disintegration that only involves acoustic power and sample volume, and which allows prediction of optimal sonication times to recover significant amounts of both natural and recombinant proteins in a given set of relevant conditions.
Prevalence of signs and symptoms of laryngopharyngeal reflux in snorers with suspected obstructive sleep apnea

Obstructive sleep apnea (OSA) is believed to be correlated with laryngopharyngeal reflux (LPR). Objective To study the prevalence of signs and symptoms of reflux in snorers with suspected OSA. Method This cross-sectional study enrolled 74 patients assessed positive for OSA with the Berlin questionnaire. The subjects were followed up at the sleep disorder ward of a university center. Studied variables included the BMI, the Epworth sleepiness scale, the reflux symptom index (RSI), the reflux finding score (RFS), and their subdomains related to increased inflammation. The correlations between sleep questionnaires, reflux scales, and their subdomains were deemed statistically significant when p < 0.05. Results Ninety-eight percent of the subjects had symptoms and signs suggestive of LPR; prevalence was significantly higher among obese individuals (p = 0.002). Conclusion The significant difference seen in the prevalence of signs of inflammation suggestive of LPR when obese and non-obese subjects with suspected OSA were compared indicates that obesity may affect inflammatory findings of the pharynx and larynx. The high prevalence of symptoms and signs of reflux in patients with suspected OSA calls for more studies on the matter.
Noise reduction and brain mapping based robust principal component analysis

Analysis of EEG activity usually raises the problem of differentiating between genuine EEG activity and that which is introduced through a variety of external influence. These artifacts may affect the outcome of the EEG recording. In this paper, wavelet denoising and band pass filter for preprocessing and a robust principal component analysis algorithm for extraction are proposed to remove the artifacts. The algorithm is designed to adaptively derive a relatively small number of decorrelated linear combinations of a set of random zero-mean variables while retaining as much of the information from the original variables as possible. The proposed method was tested in real EEG records acquired from eight subjects. The experimental result show that the proposed method can effectively remove the artifacts from all subjects.
Distinct Mutational Behaviors Differentiate Short Tandem Repeats from Microsatellites in the Human Genome

A tandem repeat’s (TR) propensity to mutate increases with repeat number, and can become very pronounced beyond a critical boundary, transforming it into a microsatellite (MS). However, a clear understanding of the mutational behavior of different TR classes and motifs and related mechanisms is lacking, as is a consensus on the existence of a boundary separating short TRs (STRs) from MSs. This hinders our understanding of MSs’ mutational properties and their effective use as genetic markers. Using indel calls for 179 individuals from 1000 Genomes Pilot-1 Project, we determined polymorphism incidence for four major TR classes, and formalized its varying relationship with repeat number using segmented regression. We observed a biphasic regime with a transition from a faster to a slower exponential growth at 9, 5, 4, and 4 repeats for mono-, di-, tri-, and tetranucleotide TRs, respectively. We used an in vitro mutagenesis assay to evaluate the contribution of strand slippage errors to mutability. STRs and MSs differ in their absolute polymorphism levels, but more importantly in their rates of mutability growth. Although strand slippage is a major factor driving mononucleotide polymorphism incidence, dinucleotide polymorphism incidence is greater than that expected due to strand slippage alone, indicating that additional cellular factors might be driving dinucleotide mutability in the human genome. Leveraging on hundreds of human genomes, we present the first comprehensive, genome-wide analysis of TR mutational behavior, encompassing several motif sizes and compositions.
Increased olfactory bulb volume and olfactory function in early blind subjects

It has been shown that the volume of the olfactory bulb (OB) changes with function. The aim of this study was to investigate whether the OB volume and the olfactory function in early blind (EB) subjects increase compared with controls. Psychophysical testing of olfactory performances and OB volumetric measurements assessed by an MRI scan were studied. Quantitative olfactory function expressed in the odor discrimination and odor-free identification scores was higher in EB subjects compared with controls. The mean of right, left and total OB volume was 65.40, 75.48, and 140.89 mm3, respectively for the EB subjects and 54.47, 52.11, and 106.60 mm3, respectively for the controls, with these differences being significant. EB subjects have superior olfactory abilities and presented with significantly higher OB volume than the sighted controls. OB plasticity may explain this compensatory mechanism between visual deprivation and enhanced olfactory perception.
Pulse Current Measurements and Rabi Oscillations in a dc SQUID Phase Qubit

We have used 2 ns pulses of current to read out the states of a Nb/AlOx/Nb dc SQUID phase qubit at 25 mK. Plotting the number of escape events that occur versus the size of the current pulse reveals a series of steps corresponding to the occupancy of different energy levels. After calibrating the measurement pulses, we fit these steps to determine the population in each level. Rabi oscillations were viewed using this technique. The single-shot measurement fidelity was theoretically analysed and the optimal single pulse in our device was determined.
Classification of human retinal microaneurysms using adaptive optics scanning light ophthalmoscope fluorescein angiography.

PURPOSE Microaneurysms (MAs) are considered a hallmark of retinal vascular disease, yet what little is known about them is mostly based upon histology, not clinical observation. Here, we use the recently developed adaptive optics scanning light ophthalmoscope (AOSLO) fluorescein angiography (FA) to image human MAs in vivo and to expand on previously described MA morphologic classification schemes. METHODS Patients with vascular retinopathies (diabetic, hypertensive, and branch and central retinal vein occlusion) were imaged with reflectance AOSLO and AOSLO FA. Ninety-three MAs, from 14 eyes, were imaged and classified according to appearance into six morphologic groups: focal bulge, saccular, fusiform, mixed, pedunculated, and irregular. The MA perimeter, area, and feret maximum and minimum were correlated to morphology and retinal pathology. Select MAs were imaged longitudinally in two eyes. RESULTS Adaptive optics scanning light ophthalmoscope fluorescein angiography imaging revealed microscopic features of MAs not appreciated on conventional images. Saccular MAs were most prevalent (47%). No association was found between the type of retinal pathology and MA morphology (P = 0.44). Pedunculated and irregular MAs were among the largest MAs with average areas of 4188 and 4116 μm(2), respectively. Focal hypofluorescent regions were noted in 30% of MAs and were more likely to be associated with larger MAs (3086 vs. 1448 μm(2), P = 0.0001). CONCLUSIONS Retinal MAs can be classified in vivo into six different morphologic types, according to the geometry of their two-dimensional (2D) en face view. Adaptive optics scanning light ophthalmoscope fluorescein angiography imaging of MAs offers the possibility of studying microvascular change on a histologic scale, which may help our understanding of disease progression and treatment response.
Compartmentation of protein folding in vivo: sequestration of non‐native polypeptide by the chaperonin–GimC system

The functional coupling of protein synthesis and chaperone‐assisted folding in vivo has remained largely unexplored. Here we have analysed the chaperonin‐dependent folding pathway of actin in yeast. Remarkably, overexpression of a heterologous chaperonin which traps non‐native polypeptides does not interfere with protein folding in the cytosol, indicating a high‐level organization of folding reactions. Newly synthesized actin avoids the chaperonin trap and is effectively channelled from the ribosome to the endogenous chaperonin TRiC. Efficient actin folding on TRiC is critically dependent on the hetero‐oligomeric co‐chaperone GimC. By interacting with folding intermediates and with TRiC, GimC accelerates actin folding at least 5‐fold and prevents the premature release of non‐native protein from TRiC. We propose that TRiC and GimC form an integrated ‘folding compartment’ which functions in cooperation with the translation machinery. This compartment sequesters newly synthesized actin and other aggregation‐sensitive polypeptides from the crowded macromolecular environment of the cytosol, thereby allowing their efficient folding.
Anterior Cruciate Ligament Injury Incidence Among Male and Female Professional Alpine Skiers

A retrospective review of anterior cruciate ligament injuries among professional alpine skiers was performed to compare sex-related differences in injury incidence. We screened 7155 ski patrollers or instructors (4537 men and 2618 women) for knee injuries before each ski season between 1991 and 1997. Screening involved a ski history questionnaire, a knee injury history questionnaire, and a knee physical examination. Any patient with an equivocal Lachman or pivot shift test was evaluated by KT-1000 arthrometry and excluded from the study if the manual maximum side-to-side difference was 3 mm or more. Thus, the study population was limited to subjects with intact anterior cruciate ligaments. Skiers injured during the study were identified through mandatory workers' compensation claims. Each injured skier was reevaluated using an injury questionnaire and physical examination. The men skied an average of 110 days per year (499,070 skier-days) and the women skied an average of 87 days per year (227,766 skier-days). Thirty-one skiing-related anterior cruciate ligament injuries were diagnosed, 21 in men and 10 in women. The incidence of ACL disruption was 4.2 injuries per 100,000 skier-days in men and 4.4 injuries per 100,000 skier-days in women. These data suggest that the incidences of anterior cruciate ligament injuries among male and female professional alpine skiers are similar.
A meta-analysis of fluctuating asymmetry in relation to heterozygosity

Fluctuating asymmetry, the random departure from perfect bilateral symmetry, is a common measure of developmental instability that has been hypothesized to be inversely correlated with heterozygosity. Although this claim has been widely repeated, several studies have reported no such association. Therefore, we test the generality of this association, using meta-analysis, by converting test statistics for the relationship between heterozygosity (H) and fluctuating asymmetry (FA) into a common effect size, the Pearson’s product-moment correlation coefficient. We have analysed a database containing 41 studies with a total of 118 individual samples. Overall we found an unweighted mean negative effect size; r=−0.09 (i.e. a negative correlation between H and FA). Significant heterogeneity in effect size was mainly caused by a difference between ectothermic and endothermic animals, and to a lesser extent by the use of different study designs (i.e. within-population vs. among-populations). Mean effect size for endothermic animals was positive and significantly different from the mean effect size for ectothermic animals. Only for within-population studies of ectothermic animals did we find a significantly negative effect size (r=−0.23 ± 0.09). The distribution of effect sizes in relation to sample size provided little evidence for patterns typical of those produced by publication bias. Our analysis suggests, at best, only a weak association between H and FA, and heterozygosity seems to explain only a very small amount of the variation in developmental instability among individuals and populations (r2=0.01 for the total material).
Life expectancy in children with cerebral palsy

Abstract Objective : To determine life expectancy of children with cerebral palsy. Design : Cohort analysis, by means of register compiled from multiple sources of ascertainment, of all children with cerebral palsy born during 1966-84 to mothers resident in Mersey region. Status of children was determined by flagging through NHS central register. Subjects : 1258 subjects with idiopathic cerebral palsy, of whom 1251 were traced and included in analysis. Main outcome measures : Effect of functional ability (ambulation, manual dexterity, and mental ability), sex, birth weight, and gestational age on survival. Results : 20 year survival for whole cohort was 89.3% for females and 86.9% for males. For subjects with no severe functional disabilities 20 year survival was 99% (95% confidence interval 98% to 100%), while subjects severely disabled in all three functional groups had 20 year survival of 50% (42% to 58%). Subjects with birth weight <=2500 g had 20 year survival of 92% (89% to 95%), while those with birth weight <2500 g had survival of 87% (84% to 89%). Subjects with gestational age of <37 weeks had 20 year survival of 93% (91% to 96%), while those with gestational age >=37 weeks had survival of 85% (83% to 88%). Birth weight and gestational age were less predictive of survival than functional disability. Best statistical model used gestational age and number of severe functional disabilities as predictors. Conclusions : Life expectancy of this cohort of children with cerebral palsy was greater than has been suggested in some previous studies. This has important implications for social, educational, and health services.
Selenium: epidemiology and basic science.

PURPOSE The trace element selenium, a constituent of antioxidant enzymes, has been proposed as a chemopreventive agent for prostate and other cancers. MATERIALS AND METHODS Published epidemiological and scientific studies relating to the potential clinical and molecular role of selenium in preventing cancer are reviewed and summarized. A unifying hypothesis underlying observations on the effect of selenium on early events in carcinogenesis is presented. RESULTS A large body of epidemiological evidence, including observational, case-control, cohort and randomized controlled clinical trials, support the proposition that selenium may prevent prostate cancer in humans. The available data suggest a beneficial effect for men with low baseline serum or toenail selenium levels, without preexisting tumors, with serum prostate specific antigen less than 4 ng/ml and in current or former smokers. Molecular data demonstrate that selenium prevents clonal expansion of nascent tumors by causing cell cycle arrest, promoting apoptosis, and modulating p53 dependent DNA repair mechanisms. CONCLUSIONS These observations give strong scientific support to ongoing clinical trials testing the ability of selenium to prevent prostate cancer and the progression of high grade prostatic intraepithelial neoplasia to cancer.
Modifying graft immunogenicity and immune response prior to transplantation: potential clinical applications of donor and graft treatment

Many studies have shown a strong association between initial graft injury and poor long‐term graft outcome. Events initiated by unspecific immune‐activating processes including brain death and ischemia/reperfusion injury occurring prior to transplantation reduce graft functionality and amplify the host immune response. These events may be particularly relevant for less than optimal grafts with reduced resistance to unspecific injuries. Several approaches to ameliorate immune activation of the graft by treating the donor or the graft have been studied. While various substances have been shown to have protective effects in experimental transplantation, only a few drugs have been tested clinically and have demonstrated beneficial effects. We review the results of experimental and clinical studies on donor or graft immunomodulation prior to transplantation and analyze the evidence to support clinical application of these strategies.