Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Nitric Oxide Inhibition on Blood Pressure and Renal Function in TGR(mRen2)27 Rats

We examined the effect of acute systemic blockade of nitric oxide synthesis on blood pressure and renal function in the monogenetically hypertensive TGR(mRen2)27 rat strain. Untreated conscious transgenic rats had significantly(p < 0.01) higher systolic blood pressures (185 ± 9versus 130 ± 5 mm Hg) and urinary albumin excretion (32± 5 versus 6 ± 2 mg/day) than did control animals without evidence of renal insufficiency. Plasma and urinary nitric oxide metabolite levels did not differ between transgenic and control rats. i.v. administration of NG-nitro-L-arginine methyl ester (10 mg/kg) to both groups caused similar elevations in systemic blood pressure(transgenic 25 ± 3 versus control 24 ± 3 mm Hg). NG-Nitro-L-arginine methyl ester induced reductions in whole kidney (1.4 ± 0.2 versus 0.7 ± 0.1 mL/min), and single nephron (23 ± 3 versus 11 ± 2 nL/min) glomerular filtration rates were significantly (p < 0.05) larger in transgenic than in control rats. This greater loss of GFR in transgenic animals was caused by a larger reduction in glomerular ultrafiltration coefficient (1.8 ± 0.2 versus 1.1 ± 0.1 nL·min-1·mm Hg-1, p < 0.05), a larger increase in afferent arteriole resistance (3.4 ± 0.2 versus 1.4 ± 0.1 dyne·s·cm-5, p < 0.05), and a subsequently smaller rise in glomerular transcapillary pressure (10 ± 1 versus 5 ± 1 mm Hg, p < 0.05). These results indicate that the renal microvasculature and glomerular hydraulic conductivity or surface area of transgenic rats are more sensitive to nitric oxide inhibition and are consistent with an important role for nitric oxide in TGR(mRen2)27 kidney function.
Naturalistic Outcomes of Evidence-Based Therapies for Borderline Personality Disorder at a University Clinic

Overall, the findings tend to picture alexithymia, as measured with the TAS-20, as combining cognitive and defensive-avoidant features in a student sample, with a small predominance of reduced cognitive complexity. This result somewhat contradicts our initial expectation that a defensive-avoidant attitude would predominate in the reactions of students to this benign exposure to sadness. However, the facet of cognitive complexity assessed here is not operatory thinking. This more benign form of cognitive deficit is more difficult to differentiate from emotional avoidance, as the former can be the result of the latter. In other words, it is likely that emotional avoidance and a lack of cognitive complexity are intimately related, and that one contributes to increase the other. Also, a student sample will not provide the entire range of alexithymic reactions seen in clinical settings.
Mutation of Asn111 in the Third Transmembrane Domain of the AT1A Angiotensin II Receptor Induces Its Constitutive Activation*

A preliminary model of the rat AT1A angiotensin II (AII) receptor (Joseph, M. P., Maigret, B., Bonnafous J.-C., Marie, J., and Scheraga, H. A. (1995) J. Protein Chem. 14, 381-398) has predicted an interaction between Asn111 located in transmembrane domain (TM) III and Tyr292 (TM VII) in the nonactivated receptor; a disruption of this interaction upon AII activation would allow Tyr292 to interact with the conserved Asp74 (TM II). The previous verification that Tyr292 is essential for receptor coupling to phospholipase C (Marie, J., Maigret, B., Joseph, M. P., Larguier, R., Nouet, S., Lombard, C., and Bonnafous, J.-C. (1994) J. Biol. Chem. 269, 20815-20818) prompted us to check the possible alterations in receptor properties upon Asn111 → Ala mutation. The mutated receptor (N111A) displayed: (i) strong constitutive activity, with amplification of the maximal phospholipase C response to AII; (ii) agonist behavior of the AT2-specific ligand CGP 42112A, [Sar1,Ile8]AII, and [Sar1,Ala8]AII, antagonists of the wild-type receptor; (iii) inverse agonism behavior of the non-peptide ligands DuP 753, LF 7-0156, and LF 8-0129. The results are discussed in the light of the allosteric ternary complex models and other described examples of constitutive activation of G protein-coupled receptors.
Quantitative analysis of multi‐protein interactions using FRET: Application to the SUMO pathway

Protein–protein binding and signaling pathways are important fields of biomedical science. Here we report simple optical methods for the determination of the equilibrium binding constant Kd of protein–protein interactions as well as quantitative studies of biochemical cascades. The techniques are based on steady‐state and time‐resolved fluorescence resonance energy transfer (FRET) between ECFP and Venus‐YFP fused to proteins of the SUMO family. Using FRET has several advantages over conventional free‐solution techniques such as isothermal titration calorimetry (ITC): Concentrations are determined accurately by absorbance, highly sensitive binding signals enable the analysis of small quantities, and assays are compatible with multi‐well plate format. Most importantly, our FRET‐based techniques enable us to measure the effect of other molecules on the binding of two proteins of interest, which is not straightforward with other approaches. These assays provide powerful tools for the study of competitive biochemical cascades and the extent to which drug candidates modify protein interactions.
Remission in schizophrenia: the relationship to baseline symptoms and changes in symptom domains during a one-year study

Abstract The concepts of partial recovery and remission have become increasingly important for the evaluation of the effectiveness of schizophrenia therapeutics. The relationship of baseline symptoms and changes in symptoms to remission of psychosis was evaluated. Fifty-six outpatients with residual schizophrenia completed a double-blind trial of olanzapine versus haloperidol and were then enrolled into a one-year open-label trial of olanzapine. Out of these 56 subjects, 13 (23%) met remission criteria at the beginning of the open-label treatment and were excluded. During the one-year study, 7/43 (16%) subjects met remission criteria. These subjects had significantly lower baseline ratings for tardive dyskinesia (TD) than subjects who did not achieve remission (1.8 ± 1.5 vs. 4.2 ± 4.6, P = 0.03). As expected, remitted subjects had significantly greater improvements in Brief Psychiatric Rating Scale total scores, positive subscale scores and scale for the Assessment of Negative Symptoms total scores. Remitted subjects also experienced a significantly greater improvement in depressive symptoms (P = 0.001), activation (P = 0.005), and Clinical Global Impressions scores (P < 0.001), as well as greater improvements in extrapyramidal symptoms (P = 0.007) and TD (P < 0.001). These results suggest that the relationship of depressive symptoms and improved side effects to the construct of remission in schizophrenia may deserve special attention. Future studies should aim to relate remission criteria to functional outcomes, cognition, and other important symptom domains.
Fibrin glue versus sutures for attaching the conjunctival autograft in pterygium surgery: a prospective observer masked clinical trial

Aims: To compare the degree of conjunctival autograft inflammation, subconjunctival haemorrhage (SCH) and graft stability following the use of sutures or fibrin glue (FG) during pterygium surgery. Methods: Prospective, observer masked, clinical trial. 40 eyes of 40 patients undergoing primary pterygium surgery with conjunctival autograft were allocated into two groups. Group 1 (n = 20) had FG (Tisseel) for attaching the conjunctival autograft, whereas group 2 (n = 20) had sutures. Standardised digital slit-lamp photographs were taken at 1 week, 1 month and 3 months postoperatively. Sutures were masked using commercially available photo-editing software. Two masked observers objectively graded the digital photographs for degree of inflammation, SCH and graft stability. Results: 34 of the 40 patients completed the study. When using FG, the degree of inflammation was significantly less than with sutures at 1 month (p = 0.019) and 3 months (p = 0.001) postoperatively. No significant difference was found for inflammation at 1 week postoperatively (p = 0.518). Conjunctival grafts secured with FG were as stable as those secured with sutures (p = 0.258, p = 0.076 and p = 0.624, at 1 week, 1 month and 3 months, respectively). No significant difference was found in degree of postoperative SCH between the groups (p = 0.417, p = 1 and p = 1, at 1 week, 1 month and 3 months, respectively). Conclusion: This is the first prospective clinical trial confirming that conjunctival grafts secured with FG during pterygium surgery not only are as stable as those secured with sutures, but also produce significantly less inflammation.
Hydrogen isotope ratio mass spectrometry and high-resolution/high-accuracy mass spectrometry in metabolite identification studies: detecting target compounds for sports drug testing.

RATIONALE In sports drug testing, comprehensive studies on the metabolism of therapeutic agents with misuse potential are necessary to identify metabolites that provide utmost retrospectivity and specificity. By commonly employed approaches minor and/or long-term metabolites in urine might remain undetected. Hence, an alternative strategy to unambiguously identify the majority of urinary metabolites including low-abundance representatives is desirable. METHODS Urine samples were collected for 20 days during an elimination study with an oral dose of 5 mg of 17α-C(2)H3-metandienone. The specimens were processed according to established sample preparation procedures (including fractionation and deconjugation) and subjected to gas chromatography/hydrogen isotope ratio mass spectrometry (GC/IRMS) analysis. Due to the deuteration of the administered drug, urinary metabolites bearing the deuterium label yield abundant and specific signals on the GC/IRMS instrument resulting from the substantially altered (2)H/(1)H ratio. The sample aliquots were measured by gas chromatography/time-of-flight (GC/Q-TOF) mass spectrometry using identical GC conditions, allowing high-resolution/high-accuracy mass data to be obtained on all urinary metabolites previously identified by IRMS. RESULTS Within the IRMS chromatograms, labeled metabolites were identified up to 20 days after administration at urinary concentration down to 0.25 ng/mL. More than 50 metabolites were observed with the earlier described long-term metabolite of metandienone, 18-nor-17β-hyroxymethyl,17α-methyl-androst-1,4,13-trien-3-one, being the most prominent glucuronidated metabolite in the studied time window. In the sulfoconjugated steroids fraction, a yet unknown metabolite was observed at m/z 283.1997 comprising the experimentally determined elemental composition of C20H21(2)H3O. CONCLUSIONS Combining IRMS with high-resolution mass spectrometry considerably facilitates and accelerates metabolite identification of deuterium-labeled compounds in urine. Of particular relevance in doping control, the principle is applicable also to other arenas of drug research, allowing the preparation and administration of e.g. radioactively labeled substances to be omitted.
Carbon Source Preference in Chemosynthetic Hot Spring Communities

ABSTRACT Rates of dissolved inorganic carbon (DIC), formate, and acetate mineralization and/or assimilation were determined in 13 high-temperature (>73°C) hot springs in Yellowstone National Park (YNP), Wyoming, in order to evaluate the relative importance of these substrates in supporting microbial metabolism. While 9 of the hot spring communities exhibited rates of DIC assimilation that were greater than those of formate and acetate assimilation, 2 exhibited rates of formate and/or acetate assimilation that exceeded those of DIC assimilation. Overall rates of DIC, formate, and acetate mineralization and assimilation were positively correlated with spring pH but showed little correlation with temperature. Communities sampled from hot springs with similar geochemistries generally exhibited similar rates of substrate transformation, as well as similar community compositions, as revealed by 16S rRNA gene-tagged sequencing. Amendment of microcosms with small (micromolar) amounts of formate suppressed DIC assimilation in short-term (<45-min) incubations, despite the presence of native DIC concentrations that exceeded those of added formate by 2 to 3 orders of magnitude. The concentration of added formate required to suppress DIC assimilation was similar to the affinity constant (Km ) for formate transformation, as determined by community kinetic assays. These results suggest that dominant chemoautotrophs in high-temperature communities are facultatively autotrophic or mixotrophic, are adapted to fluctuating nutrient availabilities, and are capable of taking advantage of energy-rich organic substrates when they become available.
The Protective Effect of the Mycobacterium bovis BCG Vaccine Is Increased by Coadministration with the Mycobacterium tuberculosis 72-Kilodalton Fusion Polyprotein Mtb72F in M. tuberculosis-Infected Guinea Pigs

ABSTRACT A tuberculosis vaccine candidate consisting of a 72-kDa polyprotein or fusion protein based upon the Mtb32 and Mtb39 antigens of Mycobacterium tuberculosis and designated Mtb72F was tested for its protective capacity as a potential adjunct to the Mycobacterium bovis BCG vaccine in the mouse and guinea pig models of this disease. Formulation of recombinant Mtb72F (rMtb72F) in an AS02A adjuvant enhanced the Th1 response to BCG in mice but did not further reduce the bacterial load in the lungs after aerosol challenge infection. In the more stringent guinea pig disease model, rMtb72F delivered by coadministration with BCG vaccination significantly improved the survival of these animals compared to BCG alone, with some animals still alive and healthy in their appearance at >100 weeks post-aerosol challenge. A similar trend was observed with guinea pigs in which BCG vaccination was boosted by DNA vaccination, although this increase was not statistically significant due to excellent protection conferred by BCG alone. Histological examination of the lungs of test animals indicated that while BCG controls eventually died from overwhelming lung consolidation, the majority of guinea pigs receiving BCG mixed with rMtb72F or boosted twice with Mtb72F DNA had mostly clear lungs with minimal granulomatous lesions. Lesions were still prominent in guinea pigs receiving BCG and the Mtb72F DNA boost, but there was considerable evidence of lesion healing and airway remodeling and reestablishment. These data support the hypothesis that the coadministration or boosting of BCG vaccination with Mtb72F may limit the lung consolidation seen with BCG alone and may promote lesion resolution and healing. Collectively, these data suggest that enhancing BCG is a valid vaccination strategy for tuberculosis that is worthy of clinical evaluation.
Alicaforsen, an antisense inhibitor of ICAM-1, as treatment for chronic refractory pouchitis after proctocolectomy: A case series

Background and aims The published data about the efficacy of the intercellular adhesion molecule-1 (ICAM-1) antisense oligonucleotide termed alicaforsen in inflammatory bowel disease (IBD) is rather inconsistent. This case series analyzes its efficacy in chronic refractory pouchitis, after proctocolectomy. Methods We performed a retrospective analysis on all patients who had received at least one dose of alicaforsen for IBD at three referral centers in Switzerland. We assessed the drug’s efficacy in patients treated for chronic refractory pouchitis, by comparing the clinical and/or endoscopic disease activity at baseline with a 2–3-month follow-up visit. Results We identified 22 patients who had received at least one dose. Among them, 13 patients were being treated for chronic refractory pouchitis. These patients had a median age of 38.0 years (95% CI 21.0–69.0) and five were female (38.5%). The median time since pouch surgery was 102.5 months (95% CI 16.0–288.0), with a median pouchitis duration of 16.0 months (95% CI 4.0–216.0). At 2–3 months after therapy, clinical and endoscopic disease activity was significantly reduced (stool frequency 9.0 versus 6.0, the Pouchitis Disease Activity Index (PDAI) clinical subscore was 4.0 versus 1.0, and the endoscopic disease activity was 4.0 versus 2.0). Clinical improvement was achieved in 11 out of 13 pouchitis patients (84.6%); however, a relapse was observed in nine of these patients (81.8%). The median time from clinical improvement to relapse was 16 weeks (95% CI 9.0–23.0). Conclusions Alicaforsen seemed to be efficacious in inducing clinical and/or endoscopic improvement in chronic refractory pouchitis and may be a promising treatment alternative in those patients; however, given the high proportion of relapse, one 6-week course of alicaforsen may not be sufficient.
Clinical implications of tumor‐associated neovascularization and current antiangiogenic strategies for the treatment of malignancies of pancreas

There is now a substantial body of evidence that tumor growth is angiogenesis‐dependent, and that neovascularization is also necessary for tumor invasion and metastasis. In addition, the assessment of microvessel count or density in a primary tumor may ultimately prove to be a significant and independent prognostic parameter for clinical outcome with respect to tumor recurrence, metastasis, and ultimately, overall patient survival. As our knowledge of the pathways, steps, and factors involved in the underlying pathogenesis of tumor‐associate angiogenesis increases, therapeutic agents and modalities aimed at inhibiting angiogenesis by blocking one or more of these steps or factors may be devised and evaluated for their potential to inhibit cancer growth and spread. Ultimately, the inhibition of tumor‐associated angiogenesis and associated processes could conceivably form the foundation upon which the treatment of aggressive malignancies is based. Cancer 1996;78:680‐7.
Direct and indirect effects of salt spray and fire on coastal heathland plant physiology and community composition

Abstract Coastal sandplain heathlands are managed largely by prescribed burning. While it is known that salt spray is an important natural disturbance contributing to the maintenance of coastal heathlands, it is unclear whether fire in coastal areas intensifies the detrimental effects of salt spray on plants growing close to the ocean. We carried out a field experiment to test the interactive effects of fire and salt spray on Martha's Vineyard, Massachusetts. Following a prescribed fire, one-meter-square plots were established in burned and unburned areas and randomly assigned a control or salt spray treatment. After ten weeks of spray treatments we found that burning stimulated new growth and salt spray consistently increased plant water stress, increased leaf necrosis, and inhibited shoot elongation. Burning did not increase the negative effects of salt spray in individual plants; salt spray and control treated plants growing in burned areas showed less water stress and leaf necrosis than those in unburned areas. This may be due to increased water availability in the burned area resulting from lower biomass and therefore lower competition for water and lower evapotranspiration rates. Burning reduced plant canopy height, decreased vascular plant species richness, and stimulated new growth in plants. Our results suggest that fire indirectly reduces the damaging effects of salt spray by increasing soil water availability and decreasing plant water stress.
Neurogenesis in Adult Hippocampus

Hippocampus as a whole has the shape of a curved tube including CA1-CA4 regions with a single layer of densely packed pyramidal neurons which curl into a tight “U” shape. One edge of the “U”, field CA4, is embedded into a backward facing strongly flexed V-shaped cortex, the dentate gyrus (DG) which comprises molecular, granular, subgranular cell layers and poly-morph layer called hilus (Figure 1). The ability to learn or form a memory requires a neuron to translate a transient signal into gene expression changes that have a long-lasting effect on synapse activity and connectivity. There are many neural circuits formed by multiclass neurons in hippocampus. One of them is the trisynaptic circuit (Figure 1) that is made up of three major cell groups: granule cells, CA3 pyramidal neurons, and CA1 pyramidal cells. The axons of layer II neurons in the entorhinal cortex (EC) project to the dentate gyrus through the perforant pathway. The dentate gyrus sends projections to the pyramidal cells in CA3 through mossy fibres. CA3 pyramidal neurons relay the information to CA1 pyramidal neurons through Schaffer collaterals. CA1 pyramidal neurons send back projections into deep-layer neurons of the EC. This kind of circuit is involved in long term potentiation (LTP) mediating learning and memory. CA3 also directly receives the projections from EC layer II neurons through the perforant pathway. CA1 receives direct input from EC layer III neurons through the temporoammonic pathway. The dentate granule cells also project to the mossy cells in the hilus and hilar interneurons, which send excitatory and inhibitory projections, respectively, back to the granule cells. The complicated neural circuits in hippocampus form the foundation of hippocampal functions.
Comportamiento productivo en cuyes (Cavia porcellus) utilizando contenidos ruminales

La investigacion se realizo en Ecuador, provincia de Tungurahua, canton Pelileo, con el proposito de evaluar el efecto de tres niveles de contenido ruminal (5, 10 y 15%) en la dieta concentrada para alimentar cuyes durante la etapa de engorde, y determinar los costos de produccion de los tratamientos. Los resultados logrados con el suministro de la dieta conformada por 15% de contenido ruminal de bovinos mas balanceado, con pesos corporales tanto a los 15 dias (763.40 g), como a los 30 dias (935.22 g), a los 45 dias (1095.27 g) y a los 60 dias (1255.34 g), consecuentemente se obtuvo ganancia en peso a los 15 dias (309.00 g), a los 30 dias (480.00 g), a los 45 dias (633.60 g) y a los 60 dias (795.33 g), reportando una conversion alimenticia tanto a los 15 dias (10.00), como a los 30 dias (12.87), a los 45 dias (17.25) y a los 60 dias (19.42). La evaluacion de la mortalidad permitio establecer que no se existieron decesos en ningun tratamiento hasta los 60 dias que duro el ensayo. Con respecto a consumo de alimento, se concluye que, en general los cuyes consumieron el total de alimento mixto proporcionado, sin dejar residuos. Del analisis bromatologico se observo que, el contenido ruminal presento 13.7% de cenizas, 9% (Nx5.7) de proteina, 12.6% de humedad, 0.098% de grasa, 34.1% de fibra cruda, 30.5% de carbohidratos totales y 173 Kcal*100 g de energia. En relacion al analisis microbiologico, se establecio que, presento 4.1 x 107 UFC/g de aerobios mesofilos, 1.4 x 104 UFC/g de mohos, 6.0 x 103 UFC/g de levaduras, cuya presencia es baja; igualmente se reporta 30(e) UFC/g de coliformes totales, <10 UFC/g de Escherichia coli y salmonella no detectada, cantidades que son bajas, lo que indica que el contenido ruminal, no se detecto presencia de microorganismos nocivos para la salud de los cuyes. Administrando el 15% de contenido ruminal mas balanceado (T3), alcanzo una relacion beneficio costo de 0.17, en donde los beneficios netos obtenidos fueron 0.17 veces lo invertido, siendo desde el punto de vista economico el tratamiento rentable.