Miracle-dz/UniFAR-FTUs huggingface dataset:
The Antioxidant Effect of Rosmarinic Acid by Different Delivery Routes in the Animal Model of Noise-Induced Hearing Loss.

HYPOTHESIS Trans-tympanic Rosmarinic Acid (RA), as compared with the systemic administration, protects against noise-induced auditory hair cell and hearing losses in rats in vivo. BACKGROUND ROS production, lipoperoxidative damage, and an imbalance of antioxidant defences play a significant role in noise-induced hearing loss. Several molecules with antioxidant properties have been tested to restore redox homeostasis; however, drug delivery system represents a challenge for their effectiveness. In our model, acute and intense noise exposure induces hearing loss, hair cell death, and oxidative stress, with an increase in superoxide production and over-expression of lipid peroxidation in cochlear structures. METHODS RA was administrated in male Wistar rats by trans-tympanic (20 μl) and systemic (10 mg/kg) modality. In systemic administration, RA was injected 1 hour before noise exposure and once daily for the following 3 days. ABRs were measured before and at days 1, 3, 7, and 30 after noise exposure. Rhodamine-phalloidin staining, dihydroethidium and 8-isoprostane immunostainings were performed to assess and quantify outer hair cells loss, superoxide production, and lipid peroxidation in the different experimental groups. RESULTS Systemic RA administration significantly decreased noise-induced hearing loss and the improvement of auditory function was paralleled by a significant reduction in cochlear oxidative stress. The trans-tympanic modality of drug administration showed a similar degree of protection both at the functional and morphological levels. CONCLUSION The effectiveness of RA given via trans-tympanic injection could be interesting for the future application of this minimally-invasive procedure in the treatment of ROS-induced hearing loss.
Control de edad en redes sociales mediante biometría facial

Actualmente, las redes sociales se han instaurado como un mecamismo muy potente de comunicaci? on y contacto entre individuos. Sin embargo, las pol? ticas de privacidad que normalmente han acompa? nado a estas redes sociales no han sido capaces de evitar el mal uso de las mismas en temas relacionados con protecci? on a menores. El caso m? as significativo es el de adultos, haci? endose pasar por menores. Este trabajo investiga la viabilidad del uso de t? ecnicas biom? etricas basadas en rasgos faciales para la detecci? on de rangos de edad, con el prop? osito de evitar que adultos se hagan pasar por menores, o incluso que ciertos menores puedan acceder a redes sociales, cuyo acceso debe estar trestringido por su edad. Los resultados muestran que es posible hacer esta distinci? on entre adultos y menores, seleccionando edades umbrales cercanas a los 18 a? nos, con tasas de acierto cercanas al 80 %, y empleando clasificadores basados en m? aquinas de vector soporte (SVMs) lineales.
[Influence of acupunction on NT-4 expression in spared root ganglion and spinal cord].

OBJECTIVE To explore the changes of the expression of NT-4 in spared dorsal root ganglia (DRG,L6) on both the operation/Acup side and the nonoperation/non-Acup side as well as in the spinal lamina II (L3, L5, L6) and Clarke' nucleus (L3) of the normal adult cats, partial dorsal rhizotomy cats, and Acup spared DRG cats so as to disclose the relation between NT-4 and the plasticity of spinal cord as well as the Acup promoting spinal cord plasticity. METHODS Twenty-five adult cats were divided into 5 groups; normal control group; unilateral partial root rhizotomy 7 d and 14 d groups (unilateral L1-L5, L7-S2 DRG were transected, but L6 DRG was spared); Acup spared DRG 7 d and 14 d groups (electro-needle stimulation was performed following unilateral partial root rhizotomy). The cats survived for 7 or 14 days after operation respectively. Bilateral L6 dorsal root ganglia and L3, L5, L6 spinal cord of every group were made into 20 microm frozen sections. Then, sections were stained under the same condition using specific NT-4 (1 : 200) antibody by the immunohistochemistry ABC method. The distribution and the number of NT-4 immunoreactive neurons in bilateral spared DRG (L6) on the operation/Acup side and the nonoperation/Acup side as well as in the, spinal lamina II (L3, L5, L6) and Clarke' nucleus (L3) of each cat were oberserved and counted. All data were analyzed by one-way ANOVA, SNK-q test and paired-t test. RESULTS Partial dorsal root rhizotomy led to continuous declination of total NT-4 immunoreactive neurons in spared ganglia, till the 14 d, while Acup reversed this tendency and made NT-4 immunoreactive neurons decrease firstly and then approach to normal level till the 14 d after Acup. In addition, Acup increased NT-4 expression in L5, L6 spinal lamina II. CONCLUSION The above finding indicate that NT-4 plays an important role in the mechanism by which Acup promotes spinal cord plasticity. Partial dorsal root rhizotomy and Acup spared DRG may exert effects on the expression of NT-4 in the/non-operrtion non-Acup side of DRG.
Interlaboratory Pig‐a gene mutation assay trial: Studies of 1,3‐propane sultone with immunomagnetic enrichment of mutant erythrocytes

An international collaborative trial was established to systematically investigate the merits and limitations of a rat in vivo Pig‐a gene mutation assay. The product of this gene is essential for anchoring CD59 to the plasma membrane, and mutations in this gene are identified by flow cytometric quantification of circulating erythrocytes without cell surface CD59 expression. Initial interlaboratory data from rats treated with several potent mutagens have been informative, but the time required for those flow cytometric analyses (∼20 min per sample) limited the number of cells that could be interrogated for the mutant phenotype. Thus, it was desirable to establish a new higher throughput scoring approach before expanding the trial to include weak mutagens or nongenotoxicants. An immunomagnetic column separation method that dramatically increases analysis rates was therefore developed (Dertinger et al. [ 2011 ]: Mutat Res 721:163‐170). To evaluate this new method for use in the international collaborative trial, studies were conducted to determine the mutagenic response of male Sprague Dawley rats treated for 3 or 28 consecutive days with several doses of 1,3‐propane sultone (1,3‐PS). Pig‐a mutant frequencies were measured over a period of several weeks and were supplemented with another indicator of genetic toxicity, peripheral blood micronucleated reticulocyte (MN‐RET) counts. 1,3‐PS was found to increase Pig‐a mutation and MN‐RET frequencies in both 3‐ and 28‐day study designs. While the greatest induction of MN‐RETs was observed in the 3‐day study, the highest Pig‐a responses were found with 28‐days of treatment. Pig‐a measurements were acquired in approximately one‐third the time required in the original method, while the number of erythrocyte and reticulocyte equivalents analyzed per sample were increased by factors of 100 and 10, respectively. The data strongly support the value of using the immunomagnetic separation technique for enumerating Pig‐a mutation frequencies. These results also demonstrate that the ongoing international trial will benefit from the inclusion of studies that are based on both acute and protracted repeat dosing schedules in conjunction with the acquisition of longitudinal data, at least until more data have been accumulated. Environ. Mol. Mutagen. 2011. © 2011 Wiley‐Liss, Inc.
SOME PHYSIOLOGIC FUNCTIONS IN PHYSICAL EDUCATION STUDENTS RE‐INVESTIGATED AFTER TWENTY‐FIVE YEARS

At the Laboratory for the Theory of Gymnastics, University of Copenhagen, all students majoring in physical education must pass a course in experimental physiology. In this course the students alternately serve as experimental subjects and as experimenters. The results are taken down in a written report that is presented as the final examination, and later kept a t the laboratory. During the summer of 1959 the laboratory achieved contact with 25 male and 11 female former physical education students who had passed the course twenty-five to thirty years previously, and persuaded them to return to the laboratory for re-investigation of certain physiologic functions. The purpose of this re-investigation was twofold: 1) to see how these formerly well trained persons compared to the average population in physical fitness, and 2) to make a “longitudinal” study of the effect of aging on some physiologic functions. The influence of aging on physiologic capacities has been studied mostly in “transectional” studies. The classic work in this line is Robinson’s (1) report on experimental studies of physical fitness in relation to age (1938). More recently, Astrand (2) and Lange Andersen (3) made contributions, and the physiological literature also contains several studies on the relation of special functions (e.g., vital capacity, blood pressure and pulmonary diffusion) to age. “Longitudinal” studies, however, are scarce; the best known probably is the comparison made by Dill, Horvath and Craig (4) of Dill’s working capacity at age 66 with that recorded more than twenty-five years earlier.
Condition Number and Backward Error for the Generalized Singular Value Decomposition

Let A, B be two matrices having the same number of columns, and let (AT, BT)T have full column rank. Certain normwise condition numbers for a finite generalized singular value (GSV) of the matrix pair {A, B} are defined, and explicit expressions of the condition numbers for a simple, nonzero GSV are derived. Moreover, a normwise backward error of {A, B} with respect to an approximate GSV and an associated approximate generalized singular vector group is also defined, and a computable formula of the backward error is obtained. The results are illustrated by numerical examples.
Efficacy of Bronchoscopic Therapies for Bronchial Mucoepidermoid Carcinoma in Children: Results from Six Patients

Aims and Background Bronchial mucoepidermoid carcinoma is a rare disease in children, and lobectomy is traditionally considered as a first-line treatment. As the tumor is characterized by intraluminal growth, low malignancy and superficial infiltration of bronchial walls, bronchoscopic interventional therapy may provide an alternative treatment with favorable results. The aim of the study was to evaluate the efficacy and safety of bronchoscopic therapies for bronchial mucoepidermoid carcinoma in children. Methods and Study design Clinical manifestations, multiple bronchoscopic interventions and outcomes in 6 children with bronchial mucoepidermoid carcinoma were retrospectively analyzed. Results The median age was 8.7 years (range 4 to 12 years). All the tumors were located in the lobar bronchus and were detected by computerized tomography. Diagnoses of low-grade mucoepidermoid carcinoma were made based on biopsies obtained via bronchoscopy. Five tumors were classified as intraluminal type and successfully eradicated by carbon dioxide cryotherapy and argon plasma coagulation under bronchoscopy. The other tumor in patient 3 was classified as the mixture type and could not be removed by a bronchoscopic, so left upper lobectomy was performed. For each patient, interventional procedures were conducted on the average for 6 times. No recurrence was detected by bronchoscopic inspections or computed tomography scans during follow-ups for 16-72 months. Conclusions Multiple bronchoscopic procedures, as alternative treatments, are effective in removing bronchial mucoepidermoid carcinoma mucoepidermoid carcinoma in children without any major complications.
Clostridial toxins

The current global outbreak of Clostridium difficile infection exemplifies the major public health threat posed by clostridial glucosylating toxins. In the western world, C. difficile infection is one of the most prolific causes of bacterial-induced diarrhea and potentially fatal colitis. Two pathogenic enterotoxins, TcdA and TcdB, cause the disease. Vancomycin and metronidazole remain readily available treatment options for C. difficile infection, but neither is fully effective as is evident by high clinical relapse and fatality rates. Thus, there is an urgent need to find an alternative therapy that preferentially targets the toxins and not the drug-resistant pathogen. Recently, we addressed these critical issues in a Nature Medicine letter, describing a novel host defense mechanism for subverting toxin virulence that we translated into prototypic allosteric therapy for C. difficile infection. In this addendum article, we provide a continued perspective of this antitoxin mechanism and consider the broader implications of therapeutic allostery in combating gut microbial pathogenesis.
Photoperiodic adaptation to breeding at different latitudes in great tits.

The photoperiodic responses in testicular growth and plasma levels of LH in nonmigratory great tits from Tromsö, Norway (69 degrees 40'N), Göteborg, Sweden (57 degrees 42'N), and Milano, Italy (45 degrees 26'N) were compared under the same lighting conditions. Male great tits, collected during midwinter, were transferred to Göteborg, and shifted from an 8-hr day in early January to a lighting regime in which day length was increased by 1/2 hr per week for 16 weeks. Control birds (only from Sweden) were kept on a 8L:16D light regime during the entire study. Blood samples were collected weekly, and laparotomies were performed every other week. Initially testicular size (approximately 1.6 mm) and plasma levels of LH (approximately 0.45 ng/ml) were similar among the four groups. Between 4 and 8 weeks after the onset of the experiment testes gradually, but significantly, increased to about 2 mm in length in the control group. This slow growth was also observed in the experimental groups. The control bird testes did not increase in size any further. The onset of the rapid testicular growth phase differed among the three experimental groups. In great tits from Milano it began when day length exceeded 11 hr; in birds from Tromsö, when day length was greater than 12 hr; and in great tits from Göteborg, when day length was between 11 and 12 hr. Once the rapid gonadal growth phase had begun it took about 6 weeks for the testes to reach maximal size (approximately 6.8 mm) in all three populations. (ABSTRACT TRUNCATED AT 250 WORDS)
Low-dose continuous combinations of hormone therapy and biochemical surrogate markers for vascular tone and inflammation: transdermal versus oral application

Objective: To compare the effects of low-dose transdermal estradiol (E2)/norethisterone acetate (NETA) patches (Estalis 25/125) with low-dose oral E2/NETA (Activelle) on cardiovascular biochemical markers after 12 and 52 weeks of treatment in postmenopausal women with intact uteri. Design: Participants were randomly assigned to receive either transdermal E2/NETA (delivering daily doses of 25 &mgr;g E2 and 125 &mgr;g NETA, applied every 3-4 d) or oral E2/NETA (1 mg E2 and 0.5 mg NETA, given daily) in this open-label study. The following markers or their stable metabolites in serum or urine were assessed: P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, matrix metalloproteinase-9, homocysteine, cyclic guanosine monophosphate, serotonin, prostacyclin, thromboxane, and urodilatin. Results: Significant decreases were found for P-selectin, intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and homocysteine for both hormone therapy (HT) regimens compared with baseline. Matrix metalloproteinase-9 was increased only by oral HT. The urinary concentrations of cyclic guanosine monophosphate, the ratio of prostacyclin to thromboxane metabolite, and the serotonin metabolite were significantly increased for both HT application modes, although the oral treatment showed a significantly greater increase than the transdermal one with respect to baseline. Urodilatin excretion was increased only by the oral regimen. Conclusions: Low-dose transdermal and oral HTs using E2 and NETA elicit favorable effects on cardiovascular biochemical markers. For most markers the magnitude of changes found were similar with respect to baseline; however, in some cases oral HT led to a significantly greater change, whereas in other cases the transdermal formulations seemed to provide greater benefits. Whether these differences may be attributed to the different administration routes or to different pharmacokinetic properties remains an open question. Overall low-dose transdermal HT seems to provoke the same benefit on the cardiovascular system as oral HT, as suggested by the results on vascular markers.
Characterization of an inwardly rectifying chloride conductance expressed by cultured rat cortical astrocytes

The biophysical and pharmacological properties of the inwardly rectifying Cl− conductance (IClh), expressed in rat type‐1 neocortical cultured astrocytes upon a long‐term treatment (1–3 weeks) with dibutyryl‐cyclic‐AMP (dBcAMP), were investigated with the whole‐cell patch‐clamp technique. Using intra‐ and extra‐cellular solutions with symmetrical high Cl− content and with the monovalent cations replaced with N‐methyl‐D‐glucamine, time‐ and voltage‐dependent Cl− currents were elicited in response to hyperpolarizing voltage steps from a holding potential of 0 mV. The inward currents activated slowly and did not display any time‐dependent inactivation. The rising phase of the current traces was best fitted with two exponential components whose time constants decreased with larger hyperpolarization. The steady‐state activation of IClh was well described by a single Boltzmann function with a half‐maximal activation potential at −62 mV and a slope of 19 mV that yields to an apparent gating charge of 1.3. The anion selectivity sequence was Cl− = Br− = I− > F− > cyclamate ≥ gluconate. External application of the putative Cl− channel blockers 4,4 diisothiocyanatostilbene‐2,2 disulphonic acid or 4‐acetamido‐4‐isothiocyanatostilbene‐2,2‐disulphonic acid did not affect IClh. By contrast, anthracene‐9‐carboxylic acid, as well as Cd2+ and Zn2+, inhibited, albeit with different potencies, the Cl− current. Taken together, these results indicate that dBcAMP‐treated cultured rat cortical astrocytes express a Cl− inward rectifier, which exhibits similar but not identical features compared with those of the cloned and heterologously expressed hyperpolarization‐activated Cl− channel ClC‐2. GLIA 21:217–227, 1997. © 1997 Wiley‐Liss, Inc.
The valosin-containing protein promotes cardiac survival through the inducible isoform of nitric oxide synthase.

AIMS Expression of the heat shock protein 22 (Hsp22) in the heart stimulates cardiac cell survival through activation of the Akt pathway and expression of the inducible nitric oxide (NO) synthase (iNOS), the mediator of ischaemic preconditioning and the most powerful prophylaxis against cardiac cell death. The goal of the present study was to elucidate the downstream effector by which Hsp22 and Akt increase iNOS expression. We tested both in vivo and in vitro the hypothesis that such an effector is the valosin-containing protein (VCP), an Akt substrate, which activates the transcription factor NF-κB, using a transgenic mouse with cardiac-specific over-expression of Hsp22, as well as isolated rat cardiac myocytes. METHODS AND RESULTS Using two-dimensional gel electrophoresis and mass spectrometry combined with immunoprecipitation, we found that Hsp22 and Akt co-localize and interact together with VCP. Adeno-mediated over-expression of VCP in isolated cardiac myocytes activated NF-κB and dose-dependently increased the expression of iNOS, which was abolished upon NF-κB inhibition. Over-expression of a dominant-negative (DN) mutant of VCP did not increase iNOS expression. VCP, but not its DN mutant, protected against chelerythrine-induced apoptosis, which was suppressed by inhibition of either NF-κB or iNOS. VCP-mediated activation of the NF-κB/iNOS pathway was also prevented upon inhibition of Akt. CONCLUSION We conclude that the Akt substrate, VCP, mediates the increased expression of iNOS downstream from Hsp22 through an NF-κB-dependent mechanism.
Quantitation of HLA Class II Protein Incorporated into Human Immunodeficiency Type 1 Virions Purified by Anti-CD45 Immunoaffinity Depletion of Microvesicles

ABSTRACT Among the many host cell-derived proteins found in human immunodeficiency virus type 1 (HIV-1), HLA class II (HLA-II) appears to be selectively incorporated onto virions and may contribute to mechanisms of indirect imunopathogenesis in HIV infection and AIDS. However, the amount of HLA-II on the surface of HIV-1 particles has not been reliably determined due to contamination of virus preparations by microvesicles containing host cell proteins, including HLA-II. Even rigorous sucrose density centrifugation is unable to completely separate HIV-1 from microvesicles. CD45, a leukocyte integral membrane protein, is found on microvesicles, yet appears to be excluded from HIV-1 particles. Exploiting this observation, we have developed a CD45-based immunoaffinity depletion method for removing CD45-containing microvesicles that yields highly purified preparations of virions. Examination of CD45-depleted HIV-1MN by high-pressure liquid chromatography, protein sequencing, and amino acid analyses determined a molar ratio of HLA-II to Gag of 0.04 to 0.05 in the purified virions, corresponding to an estimated average of 50 to 63 native HLA-II complexes (i.e., a dimer of α and β heterodimers) per virion. These values are approximately 5- to 10-fold lower than those previously determined for other virion preparations that contained microvesicles. Our observations demonstrate the utility of CD45 immunoaffinity-based approaches for producing highly purified retrovirus preparations for applications that would benefit from the use of virus that is essentially free of microvesicles.
An Overlooked Consequence of Dietary Mixing: A Varied Diet Reduces Interindividual Variance in Fitness

The determinants of diet breadth are of interest to nutritionists, ecologists, and evolutionary biologists. A recent synthesis addressing this issue found conflicting evidence for the relationship between diet breadth and mean individual fitness. Specifically, it found that while, on average, a mixed diet does increase mean fitness, in some instances, a single food provides equal (or higher) fitness than a mixed diet. Critical to ecological and evolutionary considerations of diet, however, is not only mean fitness but also variance in fitness. We combine contemporary meta-analytic methods with models of nutritional geometry to evaluate how diet affects between-individual variance in fitness within generalist consumers from a range of trophic levels. As predicted by nutritional geometry, we found that between-individual variance in fitness-related traits is higher on single-food than mixed diets. The effect was strong for longevity traits (57% higher) and reproductive traits (37%) and present but weaker for size-related traits (10%). Further, the effect became stronger as the number of available foods increased. The availability of multiple foods likely allows individuals with differing nutritional optima to customize intake, each maximizing their own fitness. Importantly, these findings may suggest that selection on traits correlated with nutritional requirements is weak in heterogeneous nutritional environments.