Prodynorphin and Proenkephalin in Cerebrospinal Fluid of Sporadic Creutzfeldt–Jakob Disease

Proenkephalin (PENK) and prodynorphin (PDYN) are endogenous opioid peptides mainly produced in the striatum and, to a lesser extent, in the cerebral cortex. Dysregulated metabolism and altered cerebrospinal fluid (CSF) levels of PENK and PDYN have been described in several neurodegenerative diseases. However, no study to date investigated these peptides in the CSF of sporadic Creutzfeldt–Jakob disease (sCJD). Using liquid chromatography-multiple reaction monitoring mass spectrometry, we evaluated the CSF PDYN- and PENK-derived peptide levels in 25 controls and 63 patients with sCJD belonging to the most prevalent molecular subtypes (MM(V)1, VV2 and MV2K). One of the PENK-derived peptides was significantly decreased in each sCJD subtype compared to the controls without a difference among subtypes. Conversely, PDYN-derived peptides were selectively decreased in the CSF of sCJD MV2K, a subtype with a more widespread overall pathology compared to the sCJD MM(V)1 and the VV2 subtypes, which we confirmed by semiquantitative analysis of cortical and striatal neuronal loss and astrocytosis. In sCJD CSF PENK and PDYN were associated with CSF biomarkers of neurodegeneration but not with clinical variables and showed a poor diagnostic performance. CSF PDYN and PENK-derived peptides had no significant diagnostic and prognostic values in sCJD; however, the distinct marker levels between molecular subtypes might help to better understand the basis of phenotypic heterogeneity determined by divergent neuronal targeting.     

Microgravity Modifies the Phenotype of Fibroblast and Promotes Remodeling of the Fibroblast–Keratinocyte Interaction in a 3D Co-Culture Model

Microgravity impairs tissue organization and critical pathways involved in the cell–microenvironment interplay, where fibroblasts have a critical role. We exposed dermal fibroblasts to simulated microgravity by means of a Random Positioning Machine (RPM), a device that reproduces conditions of weightlessness. Molecular and structural changes were analyzed and compared to control samples growing in a normal gravity field. Simulated microgravity impairs fibroblast conversion into myofibroblast and inhibits their migratory properties. Consequently, the normal interplay between fibroblasts and keratinocytes were remarkably altered in 3D co-culture experiments, giving rise to several ultra-structural abnormalities. Such phenotypic changes are associated with down-regulation of α-SMA that translocate in the nucleoplasm, altogether with the concomitant modification of the actin-vinculin apparatus. Noticeably, the stress associated with weightlessness induced oxidative damage, which seemed to concur with such modifications. These findings disclose new opportunities to establish antioxidant strategies that counteract the microgravity-induced disruptive effects on fibroblasts and tissue organization.     

Neue Azoolefine und deren saure Spaltung zu Aryldiiminen

New Azoolefines and their Acidic cleavage to Aryldiimines 3-Amino-1-aryl-3′,3′-dimethyl-pyrazolin-4-spiro-2′-oxiran-5-ones ( 3a – c ) undergo ring opening with methoxide forming methyl 3-amino-3-arylazo-propenoates ( 5a – c ). 5a – c are cleaved under acidic conditions. The main products of the cleavage of 5c with methanolic hydrochloric acid are nitrogen, 2, 4, 6-trichloro-benzen ( 6 ), 2, 4, 6-trichloro-aniline ( 9 ) and 2, 4, 6-trichlorophenylhydrazine ( 10 ). Intermediates of the cleavage of 5 are aryldiimines trapped with benzaldehyde as the corresponding benzhydrazides ( 12a , b ).     

Evaluation of the thermal performance of frame walls enhanced with paraffin and hydrated salt phase change materials using a dynamic wall simulator

The incorporation of phase change materials (PCMs) in building materials for use as latent heat storage and for potential reduction of energy requirements is an on-going field of study. In this paper, the development and testing of PCM-enhanced cellulose insulation for use in frame walls is presented. Two types of PCMs, paraffin-based and hydrated salt-based, were mixed into loose-fill cellulose insulation at concentrations of 10% and 20% (by the weight of the wallboard) in a 1.22 m × 1.22 m (48 in. × 48 in.) frame wall cavity. The thermally-enhanced frame walls were heated and allowed to cool down in a dynamic wall simulator that replicated the sun's exposure in a wall of a building on a typical summer day. Peak heat fluxes, total “daily” heat flows, and surface and air temperatures were measured and recorded. Results show that the paraffin-based PCM-enhanced insulation reduced the average peak heat flux by up to 9.2% and reduced the average total “daily” heat flow up to 1.2%. Because of the hydroscopic behavior of un-encapsulated hydrated salt, the hydrated salt-based PCM-enhanced insulation did not provide any thermal storage benefit.     

Peptide fingerprint of high quality Campania white wines by MALDI-TOF mass spectrometry

Food traceability is essential to preserve the identity of unique quality traits against frauds or commercial disputes. Therefore, there is a growing demand of new traceability systems for the collection of information related to units/batches of food ingredients and products.     

High Performance, Low-Dose Radiography Systems for Space and Remote Site Applications

Medical imaging applications using X- and gamma-rays have reached outstanding levels of complexity and performance, thanks to technology achievements in the fields of radiography, tomography and high resolution synchrotron devices. The operability of the related instrumentation resides in the availability of highly qualified specialists, as well as of medical doctors for diagnoses and treatment. This is a problem for personnel working in difficult ambient conditions as can be found in remote sites like Arctica, Antarctica and under-populated, desolated or mountainous regions on Earth. Astronauts, during long permanence at the Space Station or on future mission to Mars are potentially subject to risks such as traumas, fractures or diseases which would require semi-automated, easy-to-handle application of X-ray radiographic devices. For this purpose, the possible use of imaging instrumentation based on solid state detectors is discussed with special regard to CdZnTe pixel devices, now available with sub-mm resolution. The use of these semiconductor detectors will also allow to perform image diagnostics at much lower doses compared to the current plate-based radiographic techniques.     

Thermal Stability Threshold for Amyloid Formation in Light Chain Amyloidosis

Light chain (AL) amyloidosis is a devastating disease characterized by amyloid deposits formed by immunoglobulin light chains. Current available treatments involve conventional chemotherapy and autologous stem cell transplant. We have recently concluded a phase III trial comparing these two treatments. AL amyloidosis patients who achieve hematological complete response (CR) do not necessarily achieve organ response regardless of the treatment they received. In order to investigate the possible correlation between amyloid formation kinetics and organ response, we selected AL amyloidosis patients from the trial with kidney involvement and CR after treatment. Six patients were selected and their monoclonal immunoglobulin light chains were characterized. The proteins showed differences in their stability and their kinetics of amyloid formation. A correlation was detected at pH 7.4, showing that less stable proteins are more likely to form amyloid fibrils. AL-T03 is too unstable to form amyloid fibrils at pH 7.4. This protein was found in the only patient in the study that had organ response, suggesting that partially folded species are required for amyloid formation to occur in AL amyloidosis.     

Nonalcoholic Fatty Liver: A Possible New Target for Type 2 Diabetes Prevention and Treatment

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide. Several lines of evidence have indicated a pathogenic role of insulin resistance, and a strong association with type 2 diabetes (T2MD) and metabolic syndrome. Importantly, NAFLD appears to enhance the risk for T2MD, as well as worsen glycemic control and cardiovascular disease in diabetic patients. In turn, T2MD may promote NAFLD progression. The opportunity to take into account NAFLD in T2MD prevention and care has stimulated several clinical studies in which antidiabetic drugs, such as metformin, thiazolidinediones, GLP-1 analogues and DPP-4 inhibitors have been evaluated in NAFLD patients. In this review, we provide an overview of preclinical and clinical evidences on the possible efficacy of antidiabetic drugs in NAFLD treatment. Overall, available data suggest that metformin has beneficial effects on body weight reduction and metabolic parameters, with uncertain effects on liver histology, while pioglitazone may improve liver histology. Few data, mostly preclinical, are available on DPP4 inhibitors and GLP-1 analogues. The heterogeneity of these studies and the small number of patients do not allow for firm conclusions about treatment guidelines, and further randomized, controlled studies are needed.     

Profiling selected phytochemicals and nutrients in different tissues of the multipurpose tree Moringa oleifera L., grown in Ghana

The purpose of this new study was to determine the types and levels of major phytochemicals (non-nutrients) and nutrients in the different tissues from vegetative and flowering Moringa oleifera L. an important multipurpose crop. Rhamnose and acetyl-rhamnose-substituted glucosinolates were found in all of the M. oleifera tissues with different profiles depending on the tissue. In addition the tissues of M. oleifera had a relatively complex flavonoid profile consisting of glucosides, rutinosides, malonylglucosides and traces of acetylglucosides of kaempferol, quercetin and isorhamnetin. Fatty acid profiling of the different tissues showed that leaves were rich in palmitic (16:0) and linolenic (18:3) acid whereas seeds were predominated by oleic acid (18:1). Roots were rich in palmitic and oleic acid, whereas stems and twigs predominately contained palmitic acid. Potassium, magnesium and calcium were the predominant minerals in all of the tissues. Low levels of selenium were detected only in whole seeds.