• Crawford Hirsch posted an update 1 month, 2 weeks ago

    Myelin ensheathes selected axonal segments within the nervous system, resulting primarily in nerve impulse acceleration, as well as mechanical and trophic support for neurons. Akt inhibitor In the central and peripheral nervous systems, various proteins that contribute to the formation and stability of myelin are present, which also harbor pathophysiological roles in myelin disease. Many myelin proteins have common attributes, including small size, hydrophobic segments, multifunctionality, longevity, and regions of intrinsic disorder. With recent advances in protein biophysical characterization and bioinformatics, it has become evident that intrinsically disordered proteins (IDPs) are abundant in myelin, and their flexible nature enables multifunctionality. Here, we review known myelin IDPs, their conservation, molecular characteristics and functions, and their disease relevance, along with open questions and speculations. We place emphasis on classifying the molecular details of IDPs in myelin, and we correlate these with their various functions, including susceptibility to post-translational modifications, function in protein-protein and protein-membrane interactions, as well as their role as extended entropic chains. We discuss how myelin pathology can relate to IDPs and which molecular factors are potentially involved.Dissemination of enterobacteria that produce extended spectrum β-lactamases (ESBL) throughout the food chain has become an important health concern. This work aimed to evaluate the occurrence of ESBL-producing bacteria in foods of animal origin and to investigate the similarities between food and human isolates. The presence of beta-lactam-resistant Enterobacteriaceae was analyzed in 108 food samples, isolating 10 strains of Escherichia coli, one strain of Citrobacter freundi, and one of Hafnia alvei. E. coli isolates were compared to a group of 15 strains isolated from human patients by antibiotic susceptibility testing, characterization of ESBL genes (blaTEM, blaCTX,), multilocus sequence typing (MLST) and pulse-field gel electrophoresis (PFGE). Nineteen (14 clinical and five food) isolates carried blaCTX, 14 (six clinical and eight food) carried blaTEM, and three (one clinical and two food) carried blaSHV gen. MLST analysis revealed the prevalence of ST131 among the clinical strains, which grouped together in a PFGE cluster. Food isolates showed higher diversity and two of them (ST57) grouped with clinical strains, whereas another two belonged to clonal groups with virulence potential (ST59). In conclusion, the results showed that foods of animal origin must be regarded as a reservoir of ESBL-producing bacteria of clinical relevance, which might spread through the food chain.Etorphine-azaperone immobilisation was evaluated for translocation of Masai giraffes. Nine giraffes were darted with 0.012 ± 0.001 mg/kg etorphine and 0.07 ± 0.01 mg/kg azaperone. Once ataxic, giraffes were roped for recumbency and restrained manually. Naltrexone (3 mg/mg etorphine) was immediately given intravenously to reverse etorphine-related side effects. Protocol evaluation included physiological monitoring, blood-gas analyses, anaesthetic times, and quality scores (1 = excellent, 4 = poor). Sedation onset and recumbency were achieved in 2.6 ± 0.8 and 5.6 ± 1.4 min. Cardio-respiratory function (HR = 70 ± 16, RR = 32 ± 8, MAP = 132 ± 16) and temperature (37.8 ± 0.5) were stable. Arterial gas analysis showed hypoxaemia in some individuals (PaO2 = 67 ± 8 mmHg) and metabolic acidosis (pH = 7.23 ± 0.05, PaCO2 = 34 ± 4 mmHg, HCO3- = 12.9 ± 1.2 mmol/l). Minor startle response occurred, while higher induction-induced excitement correlated to longer inductions, worse restraint, and decreased HCO3-. After 19 ± 3.5 min of restraint, giraffes were allowed to stand and were loaded onto a chariot. Immobilisations were good and scored 2 (1-3). Inductions and recoveries were smooth and scored 1 (1-2). Translocations were uneventful and no complications occurred in 14-days boma follow-up.Neurodegenerative diseases are characterized by neuronal degeneration as well as neuroinflammation. While CD38 is strongly expressed in brain cells including neurons, astrocytes as well as microglial cells, the role played by CD38 in neurodegeneration and neuroinflammation remains elusive. Yet, CD38 expression increases as a consequence of aging which is otherwise the primary risk associated with neurodegenerative diseases, and several experimental data demonstrated that CD38 knockout mice are protected from neurodegenerative and neuroinflammatory insults. Moreover, nicotinamide adenine dinucleotide, whose levels are tightly controlled by CD38, is a recognized and potent neuroprotective agent, and NAD supplementation was found to be beneficial against neurodegenerative diseases. The aims of this review are to summarize the physiological role played by CD38 in the brain, present the arguments indicating the involvement of CD38 in neurodegeneration and neuroinflammation, and to discuss these observations in light of CD38 complex biology.Plant genomes provide information on biosynthetic pathways involved in the production of industrially relevant compounds. Genome size estimates are essential for the initiation of genome projects. The genome size of rooibos (Aspalathus linearis species complex) was estimated using DAPI flow cytometry and k-mer analyses. For flow cytometry, a suitable nuclei isolation buffer, plant tissue and a transport medium for rooibos ecotype samples collected from distant locations were identified. When using radicles from commercial rooibos seedlings, Woody Plant Buffer and Vicia faba as an internal standard, the flow cytometry-estimated genome size of rooibos was 1.24 ± 0.01 Gbp. The estimates for eight wild rooibos growth types did not deviate significantly from this value. K-mer analysis was performed using Illumina paired-end sequencing data from one commercial rooibos genotype. For biocomputational estimation of the genome size, four k-mer analysis methods were investigated A standard formula and three popular programs (BBNorm, GenomeScope, and FindGSE). GenomeScope estimates were strongly affected by parameter settings, specifically CovMax. When using the complete k-mer frequency histogram (up to 9 × 105), the programs did not deviate significantly, estimating an average rooibos genome size of 1.03 ± 0.04 Gbp. Differences between the flow cytometry and biocomputational estimates are discussed.