Unimpaired Neuropsychological Performance and Enhanced Memory Recall in Patients with Sbma: A Large Sample Comparative Study.

Peculiar cognitive profile of patients with SBMA has been described by fragmented literature. Our retrospective study reports the neuropsychological evaluations of a large cohort of patients in order to contribute towards the understanding of this field. We consider 64 neuropsychological evaluations assessing mnesic, linguistic and executive functions collected from 2013 to 2015 in patients attending at Motor Neuron Disease Centre of University of Padova. The battery consisted in: Digit Span forwards and backwards, Prose Memory test, Phonemic Verbal fluency and Trail making tests. ANCOVA statistics were employed to compare tests scores results with those obtained from a sample of healthy control subjects. Multiple linear regressions were used to study the effect on cognitive performance of CAG-repeat expansion, the degree of androgen insensitivity and their interaction to cognitive performance. Statistical analyses did not reveal altered scores in any neuropsychological tests among those adopted. Interestingly, patients performed significantly better in the Prose Memory test's score. No relevant associations were found with genetic, hormonal or clinical patients' profile. Results inconsistent with previous studies have been interpreted according to the phenomenon of somatic mosaicism. We suggest a testosterone-related and the mood state-dependant perspectives as two possible interpretations of the enhanced performances in the Prose Memory test. Further studies employing more datailed tests batteries are encouraged

The Inclusion of Concentrate with Quebracho Is Advisable in Two Forage-Based Diets of Ewes According to the In Vitro Fermentation Parameters

Simple Summary In dry, mountainous areas, ewes are fed low-quality forages (hay or straw) indoors, although they also graze in high-quality pastures when available. Concentrate supplementation is recommended to cover high nutritional requirements during lactation. Condensed tannins (CT) of quebracho (Schinopsis balansae) can be included in the concentrate to reduce methane (CH4) emissions and ruminal degradation of protein, improving the fermentation’s efficiency. Furthermore, low levels of quebracho can improve some meat and milk quality traits. The effects of the inclusion of concentrate and CT in diets depend on the level of inclusion and the quality of forage. The aim of this study was to evaluate the in vitro fermentation characteristics of diets in order to identify the most suitable one to be fed to ewes under farming conditions. The diets examined differed in quality of the forage available, comparing hay versus fresh forage diets and forage alone versus 70:30 forage:concentrate with (quebracho) or without CT (control) in each type of forage. The fresh-forage-based diets had lower gas and CH4 production and greater in vitro organic matter degradability (IVOMD) than the hay-based diets. The inclusion of quebracho concentrate increased the IVOMD in hay-based diets and reduced ammonia content in fresh-forage-based diets. Abstract Ewes receive hay or graze on fresh pastures supplemented with concentrates to fulfil their lactation requirements. Quebracho (Schinopsis balansae) can be added to change the ruminal fermentation. Fermentation parameters of forages alone and 70:30 forage:concentrate diets with control and quebracho concentrate were compared after 24 h of in vitro incubation. Fresh forage diets produced less gas (p < 0.05) and had greater IVOMD (p < 0.001), ammonia (NH3-N) content, valeric acid, branched-chain volatile fatty acid proportions, and lower propionic acid proportion than the hay diets (p < 0.01). In the hay diets, methane production increased with control concentrate (p < 0.01) and tended to decrease with quebacho concentrate (p < 0.10). The inclusion of both concentrates increased the acetic:propionic ratio (p < 0.01), and only the inclusion of quebracho concentrate increased the IVOMD (p < 0.01). In the fresh forage diets, gas and methane production increased with the inclusion of the control concentrate (p < 0.05), but methane production decreased with quebracho concentrate (p < 0.01). The inclusion of quebracho concentrate reduced the NH3-N content and valeric acid proportion (p < 0.05). In conclusion, the inclusion of quebracho concentrate would be advisable to reduce the CH4 production and NH3-N content in fresh forage diets and to increase the IVOMD in hay diets in comparison with the forages alone

Effects of total replacement of soybean meal and corn on ruminal fermentation, volatile fatty acids, protozoa concentration, and gas production

The main purpose of this study is to evaluate the effect of total replacement of soybean meal and corn with triticale and faba bean or field pea on rumen fermentation, protozoa counts, and gas production of lactating ewes. A total of 30 Sicilo-Sarde ewes were randomly allocated into three groups and were fed 1.8 kg drymatter of oat hay plus 500 g of one of three concentrates: the first concentrate (CS) was mainly composed of soybean meal, corn, and barley; the second (TFB) was formed by triticale and faba bean; and the third (TFP) was composed of triticale and field pea. The type of concentrate did not affect ruminal pH or ammonia nitrogen concentration (P > 0.05). The individual concentrations of volatile fatty acids showed a significant interaction between the type of concentrate and sampling time (P 0.05). The cumulative gas production from the in vitro fermentation, the time of incubation, and their interaction was affected by concentrate (P < 0.001). The substitution of soybean meal and corn in the concentrate with faba bean or field peas and triticale might maintain rumen parameters of dairy ewes

Use and management of pasture in the cerrado biome: Impacts on aggregation of an oxisol.

The objective of this study was to evaluate the physical quality of a dystrophic Oxisol in the Cerrado biome, by means of its aggregation, after 19 years of use and management with pasture. The treatments were soil with natural vegetation (CERR); and soil with Brachiaria decumbens cultivar Basilisk pasture, under the following four types of management: soil with maintenance-level fertilization, every two years, and with legumes (PAML); soil with maintenance-level fertilization, every two years (PAM); soil with fertilization only at implantation (PAI); and soil with degraded pasture without fertilization (PD). In November 2012, after 19 years of land use in the treatments, soil samples were collected at four locations per plot, and at two depths, 0 to 10 and 10 to 20 cm. The study evaluated the size distribution of air-dried aggregates and the distribution of water-stable aggregates, determining the water-stable weighted mean diameters (WMDws), the efficiency ratio of aggregates (ERA) and organic matter content of soil. The management of grassland with fertilizer favors the formation of larger aggregates in the soil, as well as WMDsw, ERA and the content of organic matter, improving soil physical quality, both in the 0 to 10 cm and in the 10 to 20 cm layer. Impacts on soil aggregates caused by the removal of native vegetation can be improved with the use of soil under pasture and managed with fertilization in the 10 to 20 cm layer

Bioinspired Precision Engineering of Three‐Dimensional Epithelial Stem Cell Microniches

Maintenance of the epithelium relies on stem cells residing within specialized microenvironments, known as epithelial crypts. Two‐photon polymerization (2PP) is a valuable tool for fabricating 3D micro/nanostructures for stem cell niche engineering applications. Herein, biomimetic gelatin methacrylate‐based constructs, replicating the precise geometry of the limbal epithelial crypt structures (limbal stem cell “microniches”) as an exemplar epithelial niche, are fabricated using 2PP. Human limbal epithelial stem cells (hLESCs) are seeded within the microniches in xeno‐free conditions to investigate their ability to repopulate the crypts and the expression of various differentiation markers. Cell proliferation and a zonation in cell phenotype along the z‐axis are observed without the use of exogenous signaling molecules. Significant differences in cell phenotype between cells located at the base of the microniche and those situated towards the rim are observed, demonstrating that stem cell fate is strongly influenced by its location within a niche and the geometrical details of where it resides. This study provides insight into the influence of the niche’s spatial geometry on hLESCs and demonstrates a flexible approach for the fabrication of biomimetic crypt‐like structures in epithelial tissues. This has significant implications for regenerative medicine applications and can ultimately lead to implantable synthetic “niche‐based” treatments

Crystal Structure of Crataeva tapia Bark Protein (CrataBL) and Its Effect in Human Prostate Cancer Cell Lines

A protein isolated from the bark of Crataeva tapia (CrataBL) is both a Kunitz-type plant protease inhibitor and a lectin. We have determined the amino acid sequence and three-dimensional structure of CrataBL, as well as characterized its selected biochemical and biological properties. We found two different isoforms of CrataBL isolated from the original source, differing in positions 31 (Pro/Leu); 92 (Ser/Leu); 93 (Ile/Thr); 95 (Arg/Gly) and 97 (Leu/Ser). CrataBL showed relatively weak inhibitory activity against trypsin (K-iapp = 43 mu M) and was more potent against Factor Xa (K-iapp = 8.6 mu M), but was not active against a number of other proteases. We have confirmed that CrataBL contains two glycosylation sites and forms a dimer at high concentration. The high-resolution crystal structures of two different crystal forms of isoform II verified the beta-trefoil fold of CrataBL and have shown the presence of dimers consisting of two almost identical molecules making extensive contacts (similar to 645 angstrom(2)). The structure differs from those of the most closely related proteins by the lack of the N-terminal beta-hairpin. In experiments aimed at investigating the biological properties of CrataBL, we have shown that addition of 40 mM of the protein for 48 h caused maximum growth inhibition in MTT assay (47% of DU145 cells and 43% of PC3 cells). The apoptosis of DU145 and PC3 cell lines was confirmed by flow cytometry using Annexin V/FITC and propidium iodide staining. Treatment with CrataBL resulted in the release of mitochondrial cytochrome c and in the activation of caspase-3 in DU145 and PC3 cells

Prospect for Charge Current Neutrino Interactions Measurements at the CERN-PS

Tensions in several phenomenological models grew with experimental results on neutrino/antineutrino oscillations at Short-Baseline (SBL) and with the recent, carefully recomputed, antineutrino fluxes from nuclear reactors. At a refurbished SBL CERN-PS facility an experiment aimed to address the open issues has been proposed [1], based on the technology of imaging in ultra-pure cryogenic Liquid Argon (LAr). Motivated by this scenario a detailed study of the physics case was performed. We tackled specific physics models and we optimized the neutrino beam through a full simulation. Experimental aspects not fully covered by the LAr detection, i.e. the measurements of the lepton charge on event-by-event basis and their energy over a wide range, were also investigated. Indeed the muon leptons from Charged Current (CC) (anti-)neutrino interactions play an important role in disentangling different phenomenological scenarios provided their charge state is determined. Also, the study of muon appearance/disappearance can benefit of the large statistics of CC muon events from the primary neutrino beam. Results of our study are reported in detail in this proposal. We aim to design, construct and install two Spectrometers at "NEAR" and "FAR" sites of the SBL CERN-PS, compatible with the already proposed LAr detectors. Profiting of the large mass of the two Spectrometers their stand-alone performances have also been exploited.Comment: 70 pages, 38 figures. Proposal submitted to SPS-C, CER

Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp13 helicase

The coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health challenge. While the efficacy of vaccines against emerging and future virus variants remains unclear, there is a need for therapeutics. Repurposing existing drugs represents a promising and potentially rapid opportunity to find novel antivirals against SARS-CoV-2. The virus encodes at least nine enzymatic activities that are potential drug targets. Here, we have expressed, purified and developed enzymatic assays for SARS-CoV-2 nsp13 helicase, a viral replication protein that is essential for the coronavirus life cycle. We screened a custom chemical library of over 5000 previously characterized pharmaceuticals for nsp13 inhibitors using a fluorescence resonance energy transfer-based high-throughput screening approach. From this, we have identified FPA-124 and several suramin-related compounds as novel inhibitors of nsp13 helicase activity in vitro. We describe the efficacy of these drugs using assays we developed to monitor SARS-CoV-2 growth in Vero E6 cells

3D microfabricated scaffolds and microfluidic devices for ocular surface replacement: a review

In recent years, there has been increased research interest in generating corneal substitutes, either for use in the clinic or as in vitro corneal models. The advancement of 3D microfabrication technologies has allowed the reconstruction of the native microarchitecture that controls epithelial cell adhesion, migration and differentiation. In addition, such technology has allowed the inclusion of a dynamic fluid flow that better mimics the physiology of the native cornea. We review the latest innovative products in development in this field, from 3D microfabricated hydrogels to microfluidic devices

Combined QCD and electroweak analysis of HERA data

A simultaneous fit of parton distribution functions (PDFs) and electroweak parameters to HERA data on deep inelastic scattering is presented. The input data are the neutral current and charged current inclusive cross sections which were previously used in the QCD analysis leading to the HERAPDF2.0 PDFs. In addition, the polarisation of the electron beam was taken into account for the ZEUS data recorded between 2004 and 2007. Results on the vector and axial-vector couplings of the Z boson to u- and d-type quarks, on the value of the electroweak mixing angle and the mass of the W boson are presented. The values obtained for the electroweak parameters are in agreement with Standard Model predictions.Comment: 32 pages, 10 figures, accepted by Phys. Rev. D. Small corrections from proofing process and small change to Fig. 12 and Table