Running and Swimming Differently Adapt the BDNF/TrkB Pathway to a Slow Molecular Pattern at the NMJ

Physical exercise improves motor control and related cognitive abilities and reinforces neuroprotective mechanisms in the nervous system. As peripheral nerves interact with skeletal muscles at the neuromuscular junction, modifications of this bidirectional communication by physical activity are positive to preserve this synapse as it increases quantal content and resistance to fatigue, acetylcholine receptors expansion, and myocytes’ fast-to-slow functional transition. Here, we provide the intermediate step between physical activity and functional and morphological changes by analyzing the molecular adaptations in the skeletal muscle of the full BDNF/TrkB downstream signaling pathway, directly involved in acetylcholine release and synapse maintenance. After 45 days of training at different intensities, the BDNF/TrkB molecular phenotype of trained muscles from male B6SJLF1/J mice undergo a fast-to-slow transition without affecting motor neuron size. We provide further knowledge to understand how exercise induces muscle molecular adaptations towards a slower phenotype, resistant to prolonged trains of stimulation or activity that can be useful as therapeutic tools.     

Anticancer Gold(III) Peptidomimetics: From Synthesis to in vitro and ex vivo Biological Evaluations

Five new Au^III‐peptidodithiocarbamato complexes of the type [Au^IIIBr₂(dtc‐AA₁‐AA₂‐OR] (in which AA₁=N‐methylglycine (Sar), l /d ‐Pro; AA₂=l /d ‐Ala, α‐aminoisobutyric acid (Aib); R=OtBu, triethylene glycol methyl ether), differing with regard to the amino acid sequence and/or the chiral amino acid configuration, were designed to enhance tumor selectivity and bioavailability. The gold(III)‐based moiety was functionalized to exploit the targeting properties of the peptidomimetic ligand toward two peptide transporters (namely PEPT1 and PEPT2), which are upregulated in several tumor cells. The compounds were synthesized and fully characterized, mainly by means of elemental analysis, one‐ and two‐dimensional NMR spectroscopy, FT‐IR, and UV/Vis spectrophotometry. The crystal structures of three compounds were also solved by X‐ray diffraction. In vitro cytotoxicity studies using a panel of human tumor cell lines (A549 [non‐small‐cell lung carcinoma], MCF‐7 [breast cancer], A2780 [ovarian carcinoma], H1975 [non‐small‐cell lung carcinoma], H460 [large‐cell lung carcinoma], and A431 [human epidermoid carcinoma]) showed the dtc‐Pro‐Aib‐OtBu derivative to be very effective, with GI₅₀ values much lower than those of cisplatin. This complex was thus selected for evaluating stability under physiological conditions and possible interactions with serum albumin, as well in PARP‐1 enzyme inhibition assays and preliminary ex vivo toxicity experiments on healthy rat tissues.     

Design of electrospayed non-spherical poly (l-lactide-co-glicolide) microdevices for sustained drug delivery

Polymer chain entanglements in organic solvents can be considered a key parameter in the formation of non-spherical beads when electrospraying is employed. The shape of micro/nanometric drug delivery systems plays a major role since it can affect circulation, extravasation, distribution and in vivo clearance of the devices. In this frame, we investigated the influence of polymer processing parameters on the design of polylactic-co-glycolic acid non-spherical microdevices loaded with triamcinolone acetonide (TrA), a sparingly water soluble corticosteroid, prepared by electrospraying technique through a one-step process. In particular, we verified that the formation of non-spherical MDs is related to the presence of entanglements among polymer chains to select the optimal solution to be sprayed. The addition of TrA did not substantially affect the particle morphology in terms of size, size distribution and circularity at all the tested drug loadings. Furthermore, the drug could be released for a prolonged period, with controlled and reproducible kinetics for over 3 weeks. The mathematical modeling of release profiles highlighted that the release is mainly driven by degradation, at a higher extent in the case of low drug loading.     

Improved multivariate image analysis for product quality monitoring

Product quality monitoring by image texture analysis underwent a tremendous growth in the last few years in several industrial sectors, due to the availability of low-cost digital imaging sensors. Multivariate image analysis (MIA) can be used within an image texture analysis technique to provide a spatial statistical characterization of an image. However, in most cases this spatial characterization is possible only for very local texture neighborhoods, due to the high computational cost of MIA. In this paper, the iMIA (improved Multivariate Image Analysis) algorithm is proposed, that improves over previous implementations of MIA by extending its range of applicability due to its reduced computational complexity and memory requirements. The proposed algorithm uses the Fourier transform and the convolution theorem to efficiently compute the MIA model, in such a way that the image texture can be characterized by taking into account also large neighborhood sizes. The proposed approach is applied to two case studies concerning the estimation of the fiber diameter distribution in nanostructured membranes, and the classification of paper surfaces. The results suggest that the optimum range of spatial statistics used for characterizing the image is related to the size of the main textural features.     

Innervation Pattern of the Corti Organ and Its Functional Role in Acoustic Action Potential Generation

The aim of this Chapter is to investigate the pattern of afferent and efferent nerve endings on hair cells in the Corti organ [12].     

Dietary citrus pulp reduces lipid oxidation in lamb meat

This study investigated the effect of replacing cereal concentrates with high levels of dried citrus pulp in the diet on lamb meat oxidative stability. Over 56 days, lambs were fed a barley-based concentrate (Control) or concentrates in which 24% and 35% dried citrus pulp were included to partially replace barley (Citrus 24% and Citrus 35%, respectively). Meat was aged under vacuum for 4 days and subsequently stored aerobically at 4 °C. The Control diet increased the redness, yellowness and saturation of meat after blooming (P < 0.01). Regardless of the level of supplementation, dietary dried citrus pulp strongly reduced meat lipid oxidation over 6 days of aerobic storage (P < 0.001), while colour parameters did not change noticeably over storage and their variation rate was not affected by the diet. In conclusion, replacing cereals with dried citrus pulp in concentrate-based diets might represent a feasible strategy to naturally improve meat oxidative stability and to promote the exploitation of this by-product.     

Candida albicans Tpk1p and Tpk2p isoforms differentially regulate pseudohyphal development, biofilm structure, cell aggregation and adhesins expression

Candida albicans undergoes a reversible morphological transition from single yeast cells to pseudohyphal and hyphal filaments. In this organism, cAMP-dependent protein kinase (PKA), coded by two catalytic subunits (TPK1 and TPK2) and one regulatory subunit (BCY1), mediates basic cellular processes, such as the yeast-to-hypha transition and cell cycle regulation. It is known that both Tpk isoforms play positive roles in vegetative growth and filamentation, although distinct roles have been found in virulence, stress response and glycogen storage. However, little is known regarding the participation of Tpk1p and/or Tpk2p in pseudohyphal development. This point was addressed using several C. albicans PKA mutants having heterozygous or homozygous deletions of TPK1 and/or TPK2 in different BCY1 genetic backgrounds. We observed that under hypha-only inducing conditions, all BCY1 heterozygous strains shifted growth toward pseudohyphal morphology; however, the pseudohypha:hypha ratio was higher in strains devoid of TPK2. Under pseudohypha-only inducing conditions, strains lacking TPK2 were prone to develop short and branched pseudohyphae. In tpk2 Δ/tpk2 Δ strains, biofilm architecture was markedly less dense, composed of short pseudohyphae and blastospores with reduced adhesion ability to abiotic material, suggesting a significant defect in cell adherence. Immunolabelling assays showed a decreased expression of adhesins Als1p and Als3p only in the tpk2 Δ/tpk2 Δ strain. Complementation of this mutant with a wild-type copy of TPK2 restored all the altered functions: pseudohyphae elongation, biofilm composition, cell aggregation and adhesins expression. Our study suggests that the Tpk2p isoform may be part of a mechanism underlying not only polarized pseudohyphal morphogenesis but also cell adherence.     

Effect of partially replacing dietary barley with 20% carob pulp on post-weaning growth, and carcass and meat characteristics of Comisana lambs

Sixteen male Comisana lambs were divided into two groups of eight at age 45 days. One group received a commercial pelleted diet (control) and the other group (carob) received a diet in which 20% carob pulp was used in partial replacement of barley. The animals were slaughtered at 100 days. No significant differences were observed for live weight, although the carob group ate 14% more dry matter, showing a higher conversion index (2.68 and 3.22kg dry matter per kg weight gain respectively for control and carob). The dressing percentage was higher (p < 0.05) for the control group; however, the carcasses showed no differences in the European classification system. Lightness (lean colour) was the only meat quality parameter (p < 0.05) affected by diet treatment: the carob group lambs had a higher L (?) value. This could not be attributed to ultimate pH, which was not significantly different between the two groups. In triangle tests, sensory panelists were unable to distinguish one diet treatment from the other. Instrumental tenderness was also unaffected by diet treatment.