The Contribution of Small Vessel Disease to Neurodegeneration: Focus on Alzheimer’s Disease,Parkinson’s Disease and Multiple Sclerosis

Brain small vessel disease (SVD) refers to a variety of structural and functional changes affecting small arteries and micro vessels, and manifesting as white matter changes, microbleeds and lacunar infarcts. Growing evidence indicates that SVD might play a significant role in the neurobiology of central nervous system (CNS) neurodegenerative disorders, namely Alzheimer’s disease (AD) and Parkinson’s disease (PD), and neuroinflammatory diseases, such as multiple sclerosis (MS). These disorders share different pathophysiological pathways and molecular mechanisms (i.e., protein misfolding, derangement of cellular clearance systems, mitochondrial impairment and immune system activation) having neurodegeneration as biological outcome. In these diseases, the actual contribution of SVD to the clinical picture, and its impact on response to pharmacological treatments, is not known yet. Due to the high frequency of SVD in adult-aged patients, it is important to address this issue. In this review, we report preclinical and clinical data on the impact of SVD in AD, PD and MS, with the main aim of clarifying the predictability of SVD on clinical manifestations and treatment response.     

Age-Related Changes in the Matrisome of the Mouse Skeletal Muscle

Aging is characterized by a progressive decline of skeletal muscle (SM) mass and strength which may lead to sarcopenia in older persons. To date, a limited number of studies have been performed in the old SM looking at the whole, complex network of the extracellular matrix (i.e., matrisome) and its aging-associated changes. In this study, skeletal muscle proteins were isolated from whole gastrocnemius muscles of adult (12 mo.) and old (24 mo.) mice using three sequential extractions, each one analyzed by liquid chromatography with tandem mass spectrometry. Muscle sections were investigated using fluorescence- and transmission electron microscopy. This study provided the first characterization of the matrisome in the old SM demonstrating several statistically significantly increased matrisome proteins in the old vs. adult SM. Several proteomic findings were confirmed and expanded by morphological data. The current findings shed new light on the mutually cooperative interplay between cells and the extracellular environment in the aging SM. These data open the door for a better understanding of the mechanisms modulating myocellular behavior in aging (e.g., by altering mechano-sensing stimuli as well as signaling pathways) and their contribution to age-dependent muscle dysfunction.     

Saliva Proteomics as Fluid Signature of Inflammatory and Immune-Mediated Skin Diseases

Saliva is easy to access, non-invasive and a useful source of information useful for the diagnosis of serval inflammatory and immune-mediated diseases. Following the advent of genomic technologies and -omic research, studies based on saliva testing have rapidly increased and human salivary proteome has been partially characterized. As a proteomic protocol to analyze the whole saliva proteome is not currently available, the most common aim of the proteomic analysis is to discriminate between physiological and pathological conditions. The salivary proteome has been initially investigated in several diseases: oral squamous cell carcinoma and oral leukoplakia, chronic graft-versus-host disease, and Sjögren’s syndrome. Otherwise, salivary proteomics studies in the dermatological field are still in the initial phase, thus the aim of this review is to collect the best research evidence on the role of saliva proteomics analysis in immune-mediated skin diseases to understand the direction of research in this field. The results of PRISMA analysis reported herein suggest that human saliva analysis could provide significant data for the diagnosis and prognosis of several immune-mediated and inflammatory skin diseases in the next future.     

Development and characterisation of a Y2Ti2O7-based glass-ceramic as a potential oxidation protective coating for titanium suboxide (TiOx)

A silica-based glass-ceramic, with Y₂Ti₂O₇ as the major crystalline phase, is designed, characterised and tested as an oxidation-protective coating for a titanium suboxide (TiO_x) thermoelectric material at temperatures of up to 600 °C. The optimised sinter-crystallisation treatment temperatures are found to be 1300 °C and 855 °C for a duration of 30 min, and this treatment leads to a glass-ceramic with cubic Y₂Ti₂O₇ and CaAl₂Si₂O₈ as crystalline phases. An increase of ~270 °C in the dilatometric softening temperature is observed after devitrification of the parent glass, thus further extending its working temperature range.Excellent adhesion of the glass-ceramic coating to the thermoelectric material is maintained after exposure to a temperature of 600 °C for 120 h under oxidising conditions, thus confirming the effectiveness of the T1 glass-ceramic in protecting the TiO_x material.     

High and low surface area NiO–MgO and CoO–MgO solid solutions: a study of XPS surface composition and CO oxidation activity

Oxide solid solutions NiO–MgO of high surface area were studied by XPS. The surface Ni²⁺ concentration was found to be equal, within experimental errors, to the bulk concentration. The result is analogous to that found previously for the low surface area NiO–MgO system and for both the high and low surface area systems of CoO–MgO. The catalytic oxidation of CO by O₂, on high and low surface area NiO–MgO and CoO–MgO materials, was investigated with the aim of relating the catalytic activity with transition metal ion nature and concentration. Turnover frequency data (CO₂ molecules produced per second per surface atom) show that the activity is due primarily to the transition metal ions and is not subject to the ions being in special configurations (dimers or trimers) or in special positions (edges, corners). The activity of CoO–MgO is higher than that of NiO–MgO solid solution. This revised version was published online in June 2006 with corrections to the Cover Date.     

Autothermal reforming of JP8 on a Pt/Rh catalyst: Catalyst durability studies and effects of sulfur

Autothermal reforming (ATR) of commercial grade JP8 was performed on a Pt/Rh catalyst deposited on a monolith. This study investigated catalyst performance under three test conditions: (i) 120 startup and shutdown cycles, (ii) 80 h of continuous operation with sulfur-free fuel, and (iii) 370 h of testing with JP8 containing 125 ppm of sulfur. Axial reactor temperature profiles and gas composition data showed that startup and shutdown cycling had no impact on catalyst performance. When durability testing was done with fuel containing 125 ppm of sulfur, the catalyst deactivated initially, which was reflected by a decrease in H₂ concentration and decrease in fuel conversion. However, after 250 h of operation the activity stabilized at 66% fuel conversion and product concentrations were constant for the remaining 120 h of testing. The presence of sulfur resulted in higher CO selectivity, lower H₂ concentrations, and lower fuel conversions compared to data with sulfur-free fuel. The data suggests that the presence of sulfur primarily affects steam reforming reactions, and CO oxidation. Regeneration was attempted with air and with fuel-lean combustion but initial H₂ yields and carbon selectivity were not achieved.     

A multiplex polymerase chain reaction assay for rapid detection and identification of Escherichia coli O157:H7 in foods and bovine feces

A multiplex polymerase chain reaction (PCR) assay was designed to simplify detection of Escherichia coli O157:H7 and to identify the H serogroup and the type of Shiga toxin produced by this bacterium. Primers for a plasmid-encoded hemolysin gene (hly933), and chromosomal flagella (fliCh7; flagellar structural gene of H7 serogroup), Shiga toxins (stx1, stx2), and attaching and effacing (eaeA) genes were used in a multiplex PCR for coamplification of the corresponding DNA sequences from enterohemorrhagic E. coli (EHEC) O157:H7. Enrichment cultures of ground beef, blue cheese, mussels, alfalfa sprouts, and bovine feces, artificially inoculated with various levels of E. coli O157:H7 strain 933, were subjected to a simple DNA extraction step prior to the PCR, and the resulting amplification products were analyzed by agarose gel electrophoresis. Sensitivity of the assay was < or = 1 CFU/g of food or bovine feces (initial inoculum level), and results could be obtained within 24 h. Similar detection levels were obtained with ground beef samples that underwent enrichment culturing immediately after inoculation and samples that were frozen or refrigerated prior to enrichment. The multiplex PCR facilitates detection of E. coli O157:H7 and can reduce the time required for confirmation of isolates by up to 3 to 4 days.     

Ultrahydrophobic PMMA micro- and nano-textured surfaces fabricated by optical lithography and plasma etching for X-ray diffraction studies

Polymeric (PMMA) ultrahydrophobic surfaces with contact angles up to about 170° have been fabricated and used in the context of synchrotron radiation experiments on biological droplets. The different microfabrication processes included either an optical lithography phase followed by a plasma texturing one or a single step deep reactive ion etch attack.The drying of several biological solution droplets has been monitored. Room temperature evaporation experiments (lysozyme, lactalbumin, cytochrome C, doxorubicin and synthesized peptides) finally result in the formation of easily detachable hollow residuals because of the low interaction between the ultrahydrophobic substrate and the aqueous droplet while pilot experiments (bovine insulin) in a sitting-drop environment bring to the formation of well defined crystals. Recent results about in situ X-ray diffraction experiments by SAXS & WAXS (Small and Wide Angle X-ray Scattering) μ-beam techniques confirm that the presence of such surfaces influences the formation of crystal or fibril structures. These substrates represent indeed a suitable support to study biological and inorganic droplets in a near contact-free environment exploiting the homogeneous evaporation rate induced by the ultrahydrophobicity of the system.     

Floral nectar phenolics as biochemical markers for the botanical origin of heather honey

In order to find out biochemical markers for the botanical origin of heather (Erica) honey, the phenolic metabolites present in heather floral nectar, collected from the honey-stomach of bees gathering nectar from these flowers, were analysed. The flavonoid fraction of nectar contained four main flavonoids. Two of them were quercetin and kaempferol 3-rhamnosides, and the other two were tentatively identified as myricetin 3-methyl ether and isorhamnetin 3-rhamnosides. Since the natural glycosides are hydrolysed by bee enzymes to render the corresponding aglycones, which are the metabolites detected in honey, acid hydrolysis of the nectar glycosides was achieved. The aglycones quercetin, myricetin 3-methyl ether, kaempferol and isorhamnetin were identified, as well as the gallic acid derivative ellagic acid. The analysis of Portuguese heather honey samples showed that ellagic acid was present in all the samples in significant amounts ranging between 100 g and 600 g per 100 g honey. The other nectar-derived flavonoids were also present, although some of them in very variable amounts. Ellagic acid and myricetin 3-methyl ether, which have not been detected in any of the monofloral honey samples investigated so far, with the only exception being a French honey sample of the botanically relatedCalluna (Ericaceae) which also contained ellagic acid, seem to be the most useful potential markers for the floral origin of heather honey. However, more detailed and extensive investigations are needed to prove the utility of these markers.