Assessment of blood and productive parameters in mid-lactation dairy cows fed different diets: replacement of corn silage with triticale silage

Corn crops require large amounts of resources that affect the environmental sustainability of dairy cow farming systems. The aim of the study was thus to investigate the effects of the replacement of corn silage (CS) with triticale silage (TS) by evaluating blood and productive parameters. The study lasted 7 weeks and involved two groups of 20 Italian Holstein Friesian dairy cows that were homogeneous in terms of parity ( 3±1.5 ), days in milk (DIM) ( 150±85.0 ), and daily milk production ( 26±4.6  kg). Chemical analysis of feeds was carried out weekly. Dry-matter intake was estimated daily. At the beginning and end of the trial, haematological, metabolic, and immunological parameters were analysed. At the same, time body weight and body condition score were measured. Milk characteristics were also analysed weekly. Statistical analysis was performed by ANOVA on data of the second sampling, and a non-parametric test was performed to analyse BCS. Regarding the haematological parameters in the two groups, only lymphocyte values were not in the normal range (2.86 and 2.50×109  L for CS and TS, respectively). Metabolic parameters were in the normal range except for blood ureic nitrogen (BUN; 13.65 and 14.04  mgdL-1 ), non-esterified fatty acids (NEFAs; 21.40 and 31.93  µmolL-1 ), and Cl (91.99 and 93.50  mmolL-1 ). Hair cortisol was low (0.94 and 0.91  pgmg-1 ), indicating the absence of stress signs, as confirmed by the results of other immunological parameters (serum lysozyme (SL), bactericidal activity (SBA), haptoglobin (HP), and oxygen free radicals (OFRs)). Statistical differences were not found either for haematological or biochemical parameters. The total replacement of CS with TS did not affect milk yield and composition. In conclusion, the replacement of CS by TS did not give rise to significant modifications in the parameters investigated and did not alter the health status of the animals, thus suggesting the feasibility of its introduction into the diet of mid-lactation dairy cows

The italian quaternary volcanism

The peninsular and insular Italy are punctuated by Quaternary volcanoes and their rocks constitute an important aliquot of the Italian Quaternary sedimentary successions. Also away from volcanoes themselves, volcanic ash layers are a common and frequent feature of the Quaternary records, which provide us with potential relevant stratigraphic and chronological markers at service of a wide array of the Quaternary science issues. In this paper, a broad representation of the Italian volcano logical community has joined to provide an updated comprehensive state of art of the Italian Quaternary volcanism. The eruptive history, style and dynamics and, in some cases, the hazard assessment of about thirty Quaternary volcanoes, from the north ernmost Mt. Amiata, in Tuscany, to the southernmost Pantelleria and Linosa, in Sicily Channel, are here reviewed in the light of the substantial improving of the methodological approaches and the overall knowledge achieved in the last decades in the vol canological field study. We hope that the present review can represent a useful and agile document summarising the knowledege on the Italian volcanism at the service of the Quaternary community operating in central Mediterranean area

Demographic and clinical determinants of neck pain in idiopathic cervical dystonia.

Cervical dystonia is associated with neck pain in a significant proportion of cases, but the mechanisms underlying pain are largely unknown. In this exploratory study, we compared demographic and clinical variables in cervical dystonia patients with and without neck pain from the Italian Dystonia Registry. Univariable and multivariable logistic regression analysis indicated a higher frequency of sensory trick and a lower educational level among patients with pain

Synthesis and Biological Evaluation of Novel Cinnamic Acid-Based Antimicrobials

The main antimicrobial resistance (AMR) nosocomial strains (ESKAPE pathogens such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) are the most widespread bacteria in cutaneous infections. In this work we report the synthesis, in silico skin permeability prediction, antimicrobial, antibiofilm, and wound healing properties of novel cinnamic acid-based antimicrobials (DM1–11) as novel antibacterial drugs for the treatment of ESKAPE-related skin infections. Antimicrobial and wound healing scratch assays were performed to evaluate the antibacterial properties of DM1–11. In silico skin permeability capabilities of DM1–11 were evaluated using Swiss-ADME online database. Cytotoxicity assays were performed on keratinocytes and fibroblasts. DM2, bearing a catechol group on the aromatic ring of the cinnamic portion of the molecule, possesses a significant antibacterial activity against S. aureus (MIC range 16–64 mg/L) and contrasts the biofilm-mediated S. epidermidis infection at low concentrations. Wound healing assays showed that wound closure in 48 h was observed in DM2-treated keratinocytes with a better healing pattern at all the used concentrations (0.1, 1.0, and 10 µM). A potential good skin permeation for DM2, that could guarantee its effectiveness at the target site, was also observed. Cytotoxicity studies revealed that DM2 may be a safe compound for topical use. Taking together all these data confirm that DM2 could represent a safe wound-healing topical agent for the treatment of skin wound infections caused by two of main Gram-positive bacteria belonging to ESKAPE microorganisms

Chronic exposure to l-BMAA cyanotoxin induces cytoplasmic TDP-43 accumulation and glial activation, reproducing an amyotrophic lateral sclerosis-like phenotype in mice

Background: Amyotrophic lateral sclerosis (ALS) is a progressive and often fatal neurodegenerative disease characterized by the loss of Motor Neurons (MNs) in spinal cord, motor cortex and brainstem. Despite significant efforts in the field, the exact pathogenetic mechanisms underlying both familial and sporadic forms of ALS have not been fully elucidated, and the therapeutic possibilities are still very limited. Here we investigate the molecular mechanisms of neurodegeneration induced by chronic exposure to the environmental cyanotoxin L-BMAA, which causes a form of ALS/Parkinson’s disease (PD) in several populations consuming food and/or water containing high amounts of this compound. Methods: In this effort, mice were chronically exposed to L-BMAA and analyzed at different time points to evaluate cellular and molecular alterations and behavioral deficits, performing MTT assay, immunoblot, immunofluorescence and immunohistochemistry analysis, and behavioral tests. Results: We found that cyanotoxin L-BMAA determines apoptotic cell death and a marked astrogliosis in spinal cord and motor cortex, and induces neurotoxicity by favoring TDP-43 cytoplasmic accumulation. Conclusions: Overall, our results characterize a new versatile neurotoxic animal model of ALS that may be useful for the identification of new druggable targets to develop innovative therapeutic strategies for this disease

Bace2 Is a Beta-Cell-Enriched Protease that Regulates Pancreatic Beta-Cell Function and Mass

Decreased ? cell mass and function are hallmarks of type 2 diabetes. Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human ? cells. Mice with functionally inactive Bace2 and insulin-resistant mice treated with a newly identified Bace2 inhibitor both display augmented ? cell mass and improved control of glucose homeostasis due to increased insulin levels. These results implicate Bace2 in the control of ? cell maintenance and provide a rational strategy to inhibit this protease for the expansion of functional pancreatic ? cell mass

Genetic regulation of RNA splicing in human pancreatic islets

Background: Non-coding genetic variants that influence gene transcription in pancreatic islets play a major role in the susceptibility to type 2 diabetes (T2D), and likely also contribute to type 1 diabetes (T1D) risk. For many loci, however, the mechanisms through which non-coding variants influence diabetes susceptibility are unknown. Results: We examine splicing QTLs (sQTLs) in pancreatic islets from 399 human donors and observe that common genetic variation has a widespread influence on the splicing of genes with established roles in islet biology and diabetes. In parallel, we profile expression QTLs (eQTLs) and use transcriptome-wide association as well as genetic co-localization studies to assign islet sQTLs or eQTLs to T2D and T1D susceptibility signals, many of which lack candidate effector genes. This analysis reveals biologically plausible mechanisms, including the association of T2D with an sQTL that creates a nonsense isoform in ERO1B, a regulator of ER-stress and proinsulin biosynthesis. The expanded list of T2D risk effector genes reveals overrepresented pathways, including regulators of G-protein-mediated cAMP production. The analysis of sQTLs also reveals candidate effector genes for T1D susceptibility such as DCLRE1B, a senescence regulator, and lncRNA MEG3. Conclusions: These data expose widespread effects of common genetic variants on RNA splicing in pancreatic islets. The results support a role for splicing variation in diabetes susceptibility, and offer a new set of genetic targets with potential therapeutic benefit.This research was supported by Ministerio de Ciencia e Innovación (BFU2014-54284-R, RTI2018-095666-B-I00), Medical Research Council (MR/L02036X/1), a Wellcome Trust Senior Investigator Award (WT101033), European Research Council Advanced Grant (789055), EU Horizon 2020 TDSystems (667191), ESPACE (874710), and Marie Sklodowska-Curie (643062, ZENCODE). S.B.G was supported by a Juan de la Cierva postdoctoral fellowship (MINECO; FJCI-2017-32090). M.C.A was supported by a Boehringer Ingelheim Fonds PhD fellowship. Work in CRG was supported by the CERCA Programme, Generalitat de Catalunya, Centro de Excelencia Severo Ochoa (CEX2020-001049), and support of the Spanish Ministry of Science and Innovation to the EMBL partnership. Work in Imperial College was supported by NIHR Imperial Biomedical Research Centre. M.I. was supported by a European Research Council consolidator award (101002275). D.J.M.C. and J.A.T. were supported by JDRF grants 9-2011-253, 5-SRA-2015-130-A-N, 4- SRA-2017-473-A-N, and Wellcome grants 091157/Z/10/Z and 107212/Z/15/Z, to the Diabetes and Inflammation Laboratory, Oxford, as well as the Oxford Biomedical Research Computing (BMRC) facility, a joint development between the Wellcome Centre for Human Genetics and the Big Data Institute supported by Health Data Research UK and NIHR Oxford Biomedical Research Centre, and Wellcome Trust Core Award grant 203141/Z/16/Z. D.M.J.C analysis with the UK Biobank Resource was conducted under Application 31295. A.L.G. is a Wellcome Senior Fellow in Basic Biomedical Science and was supported by the Wellcome Trust (095101, 200837, 106130, 203141), the NIDDK (U01DK105535 and UM1 DK126185), and the Oxford NIHR Biomedical Research Centre

Increased Interleukin (IL)-1β Messenger Ribonucleic Acid Expression in β-Cells of Individuals with Type 2 Diabetes and Regulation of IL-1β in Human Islets by Glucose and Autostimulation

Context: Elevated glucose levels impair islet function and survival, and it has been proposed that intraislet expression of IL-1β contributes to glucotoxicity

Genetic regulation of RNA splicing in human pancreatic islets

Abstract Background Non-coding genetic variants that influence gene transcription in pancreatic islets play a major role in the susceptibility to type 2 diabetes (T2D), and likely also contribute to type 1 diabetes (T1D) risk. For many loci, however, the mechanisms through which non-coding variants influence diabetes susceptibility are unknown. Results We examine splicing QTLs (sQTLs) in pancreatic islets from 399 human donors and observe that common genetic variation has a widespread influence on the splicing of genes with established roles in islet biology and diabetes. In parallel, we profile expression QTLs (eQTLs) and use transcriptome-wide association as well as genetic co-localization studies to assign islet sQTLs or eQTLs to T2D and T1D susceptibility signals, many of which lack candidate effector genes. This analysis reveals biologically plausible mechanisms, including the association of T2D with an sQTL that creates a nonsense isoform in ERO1B ,a regulator of ER-stress and proinsulin biosynthesis. The expanded list of T2D risk effector genes reveals overrepresented pathways, including regulators of G-protein-mediated cAMP production. The analysis of sQTLs also reveals candidate effector genes for T1D susceptibility such as DCLRE1B ,a senescence regulator, and lncRNA MEG3 .Conclusions These data expose widespread effects of common genetic variants on RNA splicing in pancreatic islets. The results support a role for splicing variation in diabetes susceptibility, and offer a new set of genetic targets with potential therapeutic benefit.info:eu-repo/semantics/publishe