Miracle-dz/UniFAR-FTUs huggingface dataset:
Minor snRNA gene delivery improves the loss of proprioceptive synapses on SMA motor neurons.

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder caused by reduced expression of the survival motor neuron (SMN) protein. SMN has key functions in multiple RNA pathways, including the biogenesis of small nuclear ribonucleoproteins (snRNPs) that are essential components of both major (U2-dependent) and minor (U12-dependent) spliceosomes. Here we investigated the specific contribution of U12 splicing dysfunction to SMA pathology through selective restoration of this RNA pathway in mouse models of varying phenotypic severity. We show that viral-mediated delivery of minor snRNA genes specifically improves select U12 splicing defects induced by SMN deficiency in cultured mammalian cells as well as in the spinal cord and dorsal root ganglia of SMA mice without increasing SMN expression. This approach resulted in a moderate amelioration of several parameters of the disease phenotype in SMA mice including survival, weight gain and motor function. Importantly, minor snRNA gene delivery improved aberrant splicing of the U12 intron-containing gene Stasimon and rescued the severe loss of proprioceptive sensory synapses on SMA motor neurons, which are early signatures of motor circuit dysfunction in mouse models. Taken together, these findings establish the direct contribution of U12 splicing dysfunction to synaptic deafferentation and motor circuit pathology in SMA.
Photoacclimation of Phaeodactylum tricornutum (Bacillariophyceae) cultures grown outdoors in photobioreactors and open ponds

The acclimation to high light of Phaeodactylum tricornutum cultures grown outdoors both in an open pond and in tubular photobioreactors (PBRs) was studied by means of chlorophyll fluorescence, pigment analysis and growth. Cultures grown in PBRs (5-cm tube diameter) at two biomass concentrations (0.3 and 0.6 g l−1) were compared with a culture grown in a 10-cm deep open pond (0.3 g l−1). Therefore, the performance of the cultures was compared on the basis of both the same biomass concentration and areal density. Cultures grown at 0.3 g l−1 in PBRs experienced the highest light stress, which resulted in dramatic changes in both chlorophyll fluorescence and photosynthesis parameters, and in low areal productivity. In this culture, the Fv/Fm ratio was 0.5 in the morning and dropped to about 0.1 within 1 h of exposure to bright sunlight. Similar behaviour was observed with the measurements of rETR, and the initial slope (αETR) of the photosynthesis curve, while the saturation irradiance parameter (Ik) increased about four-fold compared to the morning value. These changes were accompanied by a higher induction of the diadinoxanthin-cycle pigments, evidenced by an increasing ratio of diatoxanthin to diadinoxanthin during the day (up to 104% at 1400 h), and a higher value of non-photochemical quenching (NPQ) that rose to up to 1.2 in the high stress culture. The culture grown in the open pond at the same biomass concentration (0.3 g l−1) did not show sizeable changes either in pigments or in chlorophyll fluorescence parameters. Denser cultures in PBRs (0.6 g l−1) showed less dramatic changes in the photochemical parameters. Changes in the areal productivity of the cultures correlated well with changes in the photochemical parameters. Areal productivity was about 27% higher in the open pond than in PBRs when cultivated at the same concentration of 0.3 g l−1.
Nephroprotective effects of chlorogenic acid against sodium arsenite-induced oxidative stress, inflammation, and apoptosis.

BACKGROUND Chronic exposure to arsenic (As) leads to serious renal disorders. Chlorogenic acid (CGA), a phenolic compound, has several well-known physiological benefits, including antioxidant and antiinflammatory activities. The present study investigated the potential renoprotective effects of CGA on sodium arsenite (NaAsO2 )-induced kidney damage in mice. The mice were randomly allocated into five groups to receive daily treatment with CGA (200 mg/kg), NaAsO2 (5 mg/kg), NaAsO2 +CGA (100 mg/kg), NaAsO2 +CGA (200 mg/kg), or a control for 28 days. RESULTS In the NaAsO2- treated group, NaAsO2 induced significant renal dysfunction as well as oxidative damage, inflammation, and apoptosis, as demonstrated by marked increases in urea and creatinine levels accompanied by a decrease in the kidney index. Furthermore, considerable increases in malondialdehyde and nitric oxide levels and parallel decreases in various antioxidant markers (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione) levels were detected in the renal tissues of NaAsO2 -treated mice. NaAsO2 exposure was associated with marked increases in renal inflammatory marker (interleukin-1β and tumor necrosis factor-α) and apoptosis indicators including Bax and caspase-3 levels contaminant with a marked decrease in Bcl-2, an anti-apoptotic protein, in the NaAsO2- treated group compared with the control group. However, pretreatment with CGA substantially mitigated the renal injury and dysfunction associated with NaAsO2 exposure by reducing tissue inflammation and apoptosis and improving the antioxidant status. CGA pretreatment also alleviated the NaAsO2 -induced histological alterations in renal tissues. CONCLUSION Taken together, our results suggest the efficacy of CGA in alleviating As-mediated renal tissue damage. This article is protected by copyright. All rights reserved.
Computational and Crystallographic Examination of Naphthoquinone Based Diarylethene Photochromes

Photochromic compounds have a lengthy history of study and a profusion of applications that stand to gain from these studies. Among the classes of photochromic compounds, diarylethenes show desirable properties including high fatigue resistance and thermal stability, thus meeting some of the most important criteria necessary to enter the realm of practical applications. Recently, photochromic diarylethenes containing quinone functionalities have demonstrated interesting optical and solid-state properties. When properly interfaced with suitable electron withdrawing groups on the aryl component, both the ring-opening and ring-closing reactions can be achieved with visible light; this is in contrast to most other diarylethenes where UV light is required for ring closure. Unfortunately, quantitative conversion from open to closed forms is not possible. In this work, we examine the relative energies of conformations of solid-state structures observed by X-ray crystallography and evaluate their thermal stabilities based on density functional theory (DFT) calculations. Time-dependent DFT (TD–DFT) is used to model the UV-vis absorption spectra of these quinone diarylethenes. We show that spectral overlap between open and closed forms is a major hindrance to full photoconversion.
Optimal leaf area indices in C3 and C4 mono‐ and dicotyledonous species at low and high nitrogen availability

Anten, N. P R. , Schieving, F, Medina, E. , Werger, M. J. A. and Schuffelen, P 1995.Optimal leaf area indices in C, and Cj mono- and dicotyledonous species at low andhigh nitrogen availability. - Physioi. Plant. 95: 541-550.From an atialytical model it was shown that for a given total amount of nitrogen in thecanopy, there exists an optimal leaf area index (LAI), and therefore an optimal aver-age leaf nitrogen content, at which canopy photosynthesis is maximal. If the LAI is in-creased above this optimum, increased light interception will not competisate for re-duction in photosynthetic capacity of the canopy resulting fi-om reduced leaf nittogencontents. It was further derived from the model that the value of the optimal LAI in-creases with the photosynthetic nitrogen use efficiency (PNTJE) and decreases withthe canopy extinction coefficient for light (K^) and incident photon flux density (PFD)at the top ofthe canopy. These hypotheses were tested on dense stands of species withdifferent photosynthetic modes and different architectures. A garden experiment wascarried out with the C4 monocot sorghum {Sorghum bicolor [L.I Moensch cv. Pio-neer), the C? monocot rice (Oryza sativa L. cv. Araure 4), the C4 dicot amaranth (Am-aranthus cruentus L. cv. K113) and the C, dicot soybean (Glycine max [L.] Merr. cv.Williams) at two levels of tiitrogen avaiiability.The C4 species had higher PNUEs than the C, species while the dicots formed standswith higher extinction coefficients for light and had lower PNUEs than the monocots.Tbe C4 and monocot species were found to have formed more leaf area per utiit leafnitrogen (i.e. had lower leaf nitrogen contents) than the C, and dicot species, respec-tively. These results indicate that the PNUE and the extinction coefficient for light areimportant factors determining the amount of leaf area produced per unit nitrogen aswas predicted by the model.Key words - Canopy structure, C> and C4 photosynthetic pathway, dicotyledonous,leaf area index, monocotyledonous, nitrogen distribution, optimization.N. P. R Anten (corresponding author). F. Schieving. M. J A. Werner. Dept of PlantEcology and Evolutionary Biology, Utrecht Univ. F.O. B0X 800.84. 3508 TB Utrecht.The Netherlands: E. Medina. Centro de Ecologia v Ciencias Ambientales. lnst Vene-zolano de Investigaciones Cientifica. Aptdo. 21827 Caracas 1020 A. Venezuela: P.Schuffelen, lnst. fiirPflanzenbau, Lehrstuhlfiir Allgemelnen Pflanzenbau, Univ. Bonn,Katzenburg 5. D-5SI15 Bonn. Germany.
Thermal and thermal damage responses during switching bipolar radiofrequency ablation employing bipolar needles: A computational study on the effects of different electrode configuration, input voltage and ablation duration

Recent studies have demonstrated the effectiveness of switching bipolar radiofrequency ablation (bRFA) in treating liver cancer. Nevertheless, the clinical use of the treatment remains less common than conventional monopolar RFA – likely due to the lack of understanding of how the tissues respond thermally to the switching effect. The problem is exacerbated by the numerous possible switching combinations when bRFA is performed using bipolar needles, thus making theoretical deduction and experimental studies difficult. This article addresses this issue via computational modelling by examining if significant variation in the treatment outcome exists amongst six different electrode configurations defined by the X‐, C‐, U‐, N‐, Z‐ and O‐models. Results indicated that the tissue thermal and thermal damage responses varied depending on the electrode configuration and the operating conditions (input voltage and ablation duration). For a spherical tumour, 30 mm in diameter, complete ablation could not be attained in all configurations with 70 V input voltage and 5 minutes ablation duration. Increasing the input voltage to 90 V enlarged the coagulation zone in the X‐model only. With the other configurations, extending the ablation duration to 10 minutes was found to be the better at enlarging the coagulation zone.
Spatial and Temporal Patterns of Anthrax in White-Tailed Deer, Odocoileus virginianus, and Hematophagous Flies in West Texas during the Summertime Anthrax Risk Period

White-tailed deer, Odocoileus virginianus, anthrax epizootics have been frequently documented in Texas over the last two decades. Once outbreaks begin, there is evidence for the potential role of hematophagous flies as vectors for the disease. Hypotheses on the role of biting flies in the transmission of anthrax date back more than a century. Both laboratory experiments and field studies have provided evidence of a biting fly transmission pathway. In particular, several studies have implicated biting flies during severe wildlife outbreaks in North America. Despite these implications, there is a lack of spatial analysis relating flies and anthrax. Here we report on the spatial patterns of anthrax in white-tailed deer on a well-studied ranch with a documented anthrax history. These patterns were evaluated against the spatiotemporal patterns of biting flies during the anthrax risk period. Unbaited fly traps were used to collect flies across the study ranch from June through August 2005. Kernel density analysis confirmed biting fly hotspots concentrated in the areas with highest densities of deer carcasses. The average nearest neighbor index confirmed that deer carcasses were spatially clustered and density estimates suggest that these are in proximity to areas supporting high fly populations. Dual kernel density analysis of carcasses and deer population identified a large dry riverine habitat as a high anthrax risk. Fly catch rates across the period identified a similar pattern to the anthrax risk surface. The high overlap between areas of sustained high fly catch rates and anthrax cases does suggest a relationship warranting future research.
Biogeochemical control on fluorescent dissolved organic matter dynamics in a large freshwater lake (Lake Biwa, Japan)

The dynamics of fluorescent dissolved organic matter (FDOM) in the large monomictic freshwater Lake Biwa (surface area 675 km2, maximum depth 104 m) was studied from December 2010 to December 2011. The protein‐like FDOM (FDOMT) and dissolved organic carbon (DOC) showed epilimnetic accumulation (FDOMT from 4.42 ± 0.22 quinine sulfate units [QSU] to 6.30 ± 0.04 QSU; DOC from 80.8 ± 2.7 µmol L−1 to 102.7 ± 3.5 µmol L−1) between nutrient‐replete winter mixing to nutrient‐depleted stratified periods. This accumulation is attributed to the reduced heterotrophic activity following severe P‐limitation. The positive correlation between accumulated DOC and FDOMT in the epilimnion and their uniform reduction in the hypolimnion (∼ 9%) suggest FDOMT as a proxy for semi‐labile DOM. The humic‐like FDOM (FDOMM) generally increased with depth, a pattern similar to nutrients and total carbon dioxide (TCO2), but adverse to dissolved oxygen. The significant positive correlations of FDOMM with apparent oxygen utilization (r = 0.86, p < 0.001), TCO2 (r = 0.91, p < 0.001), nitrate (r = 0.83, p < 0.001), and phosphate (r = 0.76, p < 0.001) in the deeper layers suggest that FDOMM is formed during hypolimnetic mineralization. We estimated that ∼ 8% of the organic carbon degraded in the hypolimnion is transferred into humic substances. The minor contribution of DOC (6.4%) to hypolimnetic mineralization suggests that production of humic substances is mainly fueled by the mineralization of sinking biogenic particles. The production and consumption of FDOM in freshwater lakes may influence the quality and bioavailability of carbon exported from these systems.
False-Positive Malignant Diagnosis of Nodule Mimicking Lesions by Computer-Aided Thyroid Nodule Analysis in Clinical Ultrasonography Practice

This study aims to test computer-aided diagnosis (CAD) for thyroid nodules in clinical ultrasonography (US) practice with a focus towards identifying thyroid entities associated with CAD system misdiagnoses. Two-hundred patients referred to thyroid US were prospectively enrolled. An experienced radiologist evaluated the thyroid nodules and saved axial images for further offline blinded analysis using a commercially available CAD system. To represent clinical practice, not only true nodules, but mimicking lesions were also included. Fine needle aspiration biopsy (FNAB) was performed according to present guidelines. US features and thyroid entities significantly associated with CAD system misdiagnosis were identified along with the diagnostic accuracy of the radiologist and the CAD system. Diagnostic specificity regarding the radiologist was significantly (p < 0.05) higher than when compared with the CAD system (88.1% vs. 40.5%) while no significant difference was found in the sensitivity (88.6% vs. 80%). Focal inhomogeneities and true nodules in thyroiditis, nodules with coarse calcification and inspissated colloid cystic nodules were significantly (p < 0.05) associated with CAD system misdiagnosis as false-positives. The commercially available CAD system is promising when used to exclude thyroid malignancies, however, it currently may not be able to reduce unnecessary FNABs, mainly due to the false-positive diagnoses of nodule mimicking lesions.
Defibrotide inhibits donor leucocyte‐endothelial interactions and protects against acute graft‐versus‐host disease

Allogeneic hematopoietic stem cell transplantation (allo‐HCT) is an effective therapy for the treatment of high‐risk haematological malignant disorders and other life‐threatening haematological and genetic diseases. Acute graft‐versus‐host disease (aGvHD) remains the most frequent cause of non‐relapse mortality following allo‐HCT and limits its extensive clinical application. Current pharmacologic agents used for prophylaxis and treatment of aGvHD are not uniformly successful and have serious secondary side effects. Therefore, more effective and safe prophylaxis and therapy for aGvHD are an unmet clinical need. Defibrotide is a multi‐target drug successfully employed for prophylaxis and treatment of veno‐occlusive disease/sinusoidal obstruction syndrome. Recent preliminary clinical data have suggested some efficacy of defibrotide in the prevention of aGvHD after allo‐HCT. Using a fully MHC‐mismatched murine model of allo‐HCT, we report here that defibrotide, either in prophylaxis or treatment, is effective in preventing T cell and neutrophil infiltration and aGvHD‐associated tissue injury, thus reducing aGvHD incidence and severity, with significantly improved survival after allo‐HCT. Moreover, we performed in vitro mechanistic studies using human cells revealing that defibrotide inhibits leucocyte‐endothelial interactions by down‐regulating expression of key endothelial adhesion molecules involved in leucocyte trafficking. Together, these findings provide evidence that defibrotide may represent an effective and safe clinical alternative for both prophylaxis and treatment of aGvHD after allo‐HCT, paving the way for new therapeutic approaches.
Brazilian germplasm of winter squash (Cucurbita moschata D.) displays vast genetic variability, allowing identification of promising genotypes for agro-morphological traits

Winter squash fruits (Cucurbita moschata D.) are among the best sources of vitamin A precursors and constitute sources of bioactive components such as phenolic compounds and flavonoids. Approximately 70% of C. moschata seed oil is made up of unsaturated fatty acids, with high levels of monounsaturated fatty acids and components such as vitamin E and carotenoids, which represent a promising nutritional aspect in the production of this vegetable. C. moschata germplasm expresses high genetic variability, especially in Brazil. We assessed 91 C. moschata accessions, from different regions of Brazil, and maintained at the Federal University of Viçosa (UFV) Vegetable Germplasm Bank, to identify early-flowering accessions with high levels of carotenoids in the fruit pulp and high yields of seed and seed oil. Results showed that the accessions have high variability in the number and mass of seeds per fruit, number of accumulated degree-days for flowering, total carotenoid content, and fruit productivity, which allowed selection for considerable gains in these characteristics. Analysis of the correlation between these characteristics provided information that will assist in selection to improve this crop. Cluster analysis resulted in the formation of 16 groups, confirming the variability of the accessions. Per se analysis identified accessions BGH-6749, BGH-5639, and BGH-219 as those with the earliest flowering. Accessions BGH-5455A and BGH-5598A had the highest carotenoid content, with averages greater than 170.00 μg g-1 of fresh mass. With a productivity of 0.13 t ha-1, accessions BGH-5485A, BGH-4610A, and BGH-5472A were the most promising for seed oil production. These last two accessions corresponded to those with higher seed productivity, averaging 0.58 and 0.54 t ha-1, respectively. This study confirms the high potential of this germplasm for use in breeding for promotion of earlier flowering and increase in total content of fruit pulp carotenoids and in seed and seed oil productivity.
The complex analysis of stem canker (Leptosphaeria spp.) risk factors to winter oilseed rape.

Long vegetation period, good quality soils and annual rainfall about 700 mm make Paczków Foothills a suitable mezoregion for production of winter oilseed rape. The aim of this work was a complex analysis of stem canker risk to oilseed rape in this region, caused by two ascomycete fungi Leptosphaeria maculans and L. biglobosa, with the stress on primary inoculum production that makes the pathogens successful in plant infection. The studies were done in Charbielin near Głuchołazy for three consecutive seasons from 2005/06 to 2007/08, using both conventional aerobiological techniques (spore trapping) and quantitative molecular analyses (qPCR). Great differences were found in profiles of ascospore release, linked with the speed of pseudothecial maturation of L. maculans and L. biglobosa. The highest concentrations of the ascospores ranged from 6 to 500 ascospores per 1 m3 in the autumn and from 0.4 to 35 per 1 m3 in the spring. Independently of the season the highest ascospore concentrations were detected in daytime. The results of microscope detection of fungal spores from spore traps were correlated with quantitative detection of fungal DNA using Real-Time PCR in the presence of SYBR Green and species specific primers. The dominating species was L. biglobosa, which is regarded less pathogenic, but more difficult to eradicate with fungicides. Leptosphaeria maculans was prevalent in oilseed rape plants, probably due to a higher number of days when ascospores of this species were released. Under the encountered weather conditions the pathogens causing stem canker of brassicas found conditions greatly promoting the production of primary inoculum and establishing infections in winter oilseed rape plants. Phytopathologia 55: 43–59 © The Polish Phytopathological Society, Poznań 2010 ISSN 2081-1756 This work was supported by the research project from the Polish Ministry of Science and Higher Education (N N310 086436).