Genetic Architecture and Molecular,Imaging and Prodromic Markers in Dementia with Lewy Bodies: State of the Art,Opportunities and Challenges

Dementia with Lewy bodies (DLB) is one of the most common causes of dementia and belongs to the group of α-synucleinopathies. Due to its clinical overlap with other neurodegenerative disorders and its high clinical heterogeneity, the clinical differential diagnosis of DLB from other similar disorders is often difficult and it is frequently underdiagnosed. Moreover, its genetic etiology has been studied only recently due to the unavailability of large cohorts with a certain diagnosis and shows genetic heterogeneity with a rare contribution of pathogenic mutations and relatively common risk factors. The rapid increase in the reported cases of DLB highlights the need for an easy, efficient and accurate diagnosis of the disease in its initial stages in order to halt or delay the progression. The currently used diagnostic methods proposed by the International DLB consortium rely on a list of criteria that comprises both clinical observations and the use of biomarkers. Herein, we summarize the up-to-now reported knowledge on the genetic architecture of DLB and discuss the use of prodromal biomarkers as well as recent promising candidates from alternative body fluids and new imaging techniques.     

Mechanical properties of epoxy networks based on DGEBA and aliphatic amines

The mechanical properties of epoxy networks based on diglycidyl ether of bisphenol A epoxy resin cured with various linear aliphatic amines, such as ethylenediamine, diethylenetriamine, triethylenetetramine, tetraethylenepentamine, and cyclic amines such as 1‐(2‐aminoethyl)piperazine and isophorone diamine, were studied. General characteristics such as T_g, density, and packing density, were determined and related to the structure and funcionality of the curing agent. Dynamic mechanical spectra were used to study both the α and β relaxations. Tensile and the flexural tests were used to determine the Young's and flexural modulus, and fracture strength all in the glassy state. Furthermore, linear elastic fracture mechanics was used to determine K_IC. As a rule, isophorone diamine network presented the higher tensile and flexure modulus while 1‐(2‐aminoethyl)piperazine gave the highest toughness properties. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Rheological,mechanical, and morphological studies of epoxy/poly(methyl methacrylate) semi‐interpenetrating polymer networks

Semi‐interpenetrating polymer networks (semi‐IPNs) of epoxy resin and poly(methyl methacrylate) (PMMA) were synthesized. Methyl methacrylate (MMA) was polymerized by free radical mechanism with azo‐bis‐isobutyronitrile in the presence of oligomeric epoxy resin (DGEBA), and hexahydrophthalic anhydride as crosslinking agent. The gelation and vitrification transitions during cure/polymerization processes have been examined using parallel‐plates rheological technique. From differential scanning calorimetry and rheological techniques, it was suggested that both curing and polymerization processes occur simultaneously. However, the gelation time was longer for the semi‐IPN than those observed for the cure of pure DGEBA or polymerization of MMA. The gelation time increased significantly when 5% of MMA was employed, suggesting a diluent effect of the monomer. Higher amount of MMA resulted in a decrease of gel time, probably because of the simultaneous polymerization of MMA during the curing process. Structural examination of the semi‐IPNs, using scanning electron microscopy, revealed phase separation in nanoscale size for semi‐IPNs containing PMMA at concentrations up to 15%. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Master batch approach for developing PVDF/EVA/CNT nanocomposites with co-continuous morphology and improved electrical conductivity

Conducting polymer composites constituted by co-continuous poly (vinylidene fluoride) (PVDF)/ ethylene- vinyl acetate copolymer (EVA) blends with multiwalled carbon nanotube (CNT) were prepared by melt mixing using different procedures. The effect of the master batch approach on the conductivity, morphology, mechanical, thermal and rheological properties of PVDF/EVA/CNT nanocomposites was compared with that based on one step mixing strategy. The selective extraction experiments revealed that CNT was preferentially localized in the EVA phase in all situations, even when PVDF@CNT master batch was employed. Nanocomposites prepared with EVA@CNT master batch displayed higher conductivity, whose value reached around 10⁻¹ S m⁻¹ with the addition of 0.56 vol% of CNT. The better electrical performance was attributed to the better distribution of the filler, as indicated by transmission electron microscopy and rheological behavior. The electrical and rheological behavior were also investigated as a function of the CNT content.     

Superior Cerebellar Atrophy: An Imaging Clue to Diagnose ITPR1-Related Disorders

The inositol 1,4,5-triphosphate receptor type 1 (ITPR1) gene encodes an InsP₃-gated calcium channel that modulates intracellular Ca²⁺ release and is particularly expressed in cerebellar Purkinje cells. Pathogenic variants in the ITPR1 gene are associated with different types of autosomal dominant spinocerebellar ataxia: SCA15 (adult onset), SCA29 (early-onset), and Gillespie syndrome. Cerebellar atrophy/hypoplasia is invariably detected, but a recognizable neuroradiological pattern has not been identified yet. With the aim of describing ITPR1-related neuroimaging findings, the brain MRI of 14 patients with ITPR1 variants (11 SCA29, 1 SCA15, and 2 Gillespie) were reviewed by expert neuroradiologists. To further evaluate the role of superior vermian and hemispheric cerebellar atrophy as a clue for the diagnosis of ITPR1-related conditions, the ITPR1 gene was sequenced in 5 patients with similar MRI pattern, detecting pathogenic variants in 4 of them. Considering the whole cohort, a distinctive neuroradiological pattern consisting in superior vermian and hemispheric cerebellar atrophy was identified in 83% patients with causative ITPR1 variants, suggesting this MRI finding could represent a hallmark for ITPR1-related disorders.     

Sacha inchi (Plukenetia volubilis L.) shell: an alternative source of phenolic compounds and antioxidants

Sacha inchi seed (SI) is known as a rich source of oil with high content of polyunsaturared fatty acids of the ω‐3 and ω‐6 type (~85% of total fatty acids). However, few studies have focused on the use of by‐products from the seed. The aim of this study was to characterise the main phenolic families present in SI shell and to evaluate the best extraction solvent for the extraction of phenolic compounds (PC) and antioxidant capacity (AOXC). The PC content corresponded to 74.5 ± 5.1 mg g^?1 of which 93.1% were condensed tannins and the remaining compounds corresponded to free and bound phenolic acids, hydrolyzable tannins, flavonoids and flavanoids. Protocatechic and p‐coumaric acids but also hydroxycinammic acid derivatives of ferulic and o‐coumaric type and lignan derivatives were identified. Acetone containing solvents favoured the extraction of higher amounts of total PC and AOXC. This study highlights the potential use of SI shell as a novel and alternative source of PC antioxidants for the nutraceutical and/or functional food industries.     

Serum lipid analysis and isotopic enrichment is suggestive of greater lipogenesis in young long-term cannabis users: A secondary analysis of a case–control study

Cannabis is now legal in many countries and while numerous studies have reported on its impact on cognition and appetite regulation, none have examined fatty acid metabolism in young cannabis users. We conducted an exploratory analysis to evaluate cannabis impact on fatty acid metabolism in cannabis users (n = 21) and non-cannabis users (n = 16). Serum levels of some saturated and monounsaturated fatty acids, including palmitic, palmitoleic, and oleic acids were higher in cannabis users compared to nonusers. As palmitic acid can be derived from diet or lipogenesis from sugars, we evaluated lipogenesis using a de novo lipogenesis index (palmitate/linoleic acid) and carbon-specific isotope analysis, which allows for the determination of fatty acid ¹³C signature. The significantly higher de novo lipogenesis index in the cannabis users group along with a more enriched ¹³C signature of palmitic acid suggested an increase in lipogenesis. In addition, while serum glucose concentration did not differ between groups, pyruvate and lactate were lower in the cannabis user group, with pyruvate negatively correlating with palmitic acid. Furthermore, the endocannabinoid 2-arachidonoylglycerol was elevated in cannabis users and could contribute to lipogenesis by activating the cannabinoid receptor 1. Because palmitic acid has been suggested to increase inflammation, we measured peripheral cytokines and observed no changes in inflammatory cytokines. Finally, an anti-inflammatory metabolite of palmitic acid, palmitoylethanolamide was elevated in cannabis users. Our results suggest that lipogenic activity is increased in cannabis users; however, future studies, including prospective studies that control dietary intake are required.     

Synthetic Activity of Recombinant Whole Cell Biocatalysts Containing 2-Deoxy-D-ribose-5-phosphate Aldolase from Pectobacterium atrosepticum

In nature 2-deoxy-D-ribose-5-phosphate aldolase (DERA) catalyses the reversible formation of 2-deoxyribose 5-phosphate from D-glyceraldehyde 3-phosphate and acetaldehyde. In addition, this enzyme can use acetaldehyde as the sole substrate, resulting in a tandem aldol reaction, yielding 2,4,6-trideoxy-D-erythro-hexapyranose, which spontaneously cyclizes. This reaction is very useful for the synthesis of the side chain of statin-type drugs used to decrease cholesterol levels in blood. One of the main challenges in the use of DERA in industrial processes, where high substrate loads are needed to achieve the desired productivity, is its inactivation by high acetaldehyde concentration. In this work, the utility of different variants of Pectobacterium atrosepticum DERA (PaDERA) as whole cell biocatalysts to synthesize 2-deoxyribose 5-phosphate and 2,4,6-trideoxy-D-erythro-hexapyranose was analysed. Under optimized conditions, E. coli BL21 (PaDERA C-His AA C49M) whole cells yields 99 % of both products. Furthermore, this enzyme is able to tolerate 500 mM acetaldehyde in a whole-cell experiment which makes it suitable for industrial applications.     

In Vivo Evaluation of Sgc8-c Aptamer as a Molecular Imaging Probe for Colon Cancer in a Mouse Xenograft Model

Recent biotechnological applications in the field of clinical oncology led to the identification of new biomarkers as molecular targets of cancer, and to broad developments in the field of personalized medicine. Aptamers are oligonucleotides (ssDNA or RNA) that are selected to specifically recognize a molecular target with high affinity and specificity. Based on this, new horizons for their use as molecular imaging probes are being explored. The objective of this work was to evaluate the Sgc8-c aptamer conjugated with Alexa Fluor 647 fluorophore as an imaging probe in a colon tumor xenograft mouse model, with potential application in molecular imaging. In this study, the LS174T cell line was used to induce colorectal adenocarcinoma in nude mice. After confirmation of PTK7 overexpression by immunohistochemistry, in vivo studies were performed. Pharmacokinetic, in vivo and ex vivo biodistribution imaging, and a competition assay were evaluated by fluorescence imaging. In vivo visualization of the probe in the tumors was assessed two hours after aptamer probe administration, exhibiting excellent tumor-to-background ratios in biodistribution studies and high specificity in the competition test. Our results demonstrated the functionality of Scg8-c as an imaging probe for colon cancer, with potential clinical applications.     

The lifespan of “informetrics” on the Web: An eight year study (1998–2006)

The World Wide Web is growing at an enormous speed, and has become an indispensable source for information and research. New pages are constantly added, but there are additional processes as well: pages are moved or removed and/or their content changes. We report here the results of an eight year long project started in 1998, when multiple search engines were used to identify a set of pages containing the term informetrics. Data collection was repeated once a year for the last eight years (with the exception of 2000 and 2001) using both search engines and revisiting previously identified pages. The results show that the number of pages grew from 866 in 1998 to 28,914 in 2006 — a 33-fold growth. Besides the obvious growth of the topic on the Web, we observed both decay (pages disappearing from the Web) and modification. Even though most of the pages from 1998 either disappeared or ceased to contain the term informetrics, 165 pages (19.1%) still exist in 2006 and contain the search term. We followed the “fate” of these 165 pages: characterized the publishers, the contents and the changes that occurred the whole period. In recent years e-print servers and publishers’ sites became sources of large number of pages related to informetrics. Longitudinal studies following the evolution of a topic on the Web are very important, since they provide insights about content and the underlying Web processes.