The Neurovascular Unit Dysfunction in Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide. Histopathologically, AD presents with two hallmarks: neurofibrillary tangles (NFTs), and aggregates of amyloid β peptide (Aβ) both in the brain parenchyma as neuritic plaques, and around blood vessels as cerebral amyloid angiopathy (CAA). According to the vascular hypothesis of AD, vascular risk factors can result in dysregulation of the neurovascular unit (NVU) and hypoxia. Hypoxia may reduce Aβ clearance from the brain and increase its production, leading to both parenchymal and vascular accumulation of Aβ. An increase in Aβ amplifies neuronal dysfunction, NFT formation, and accelerates neurodegeneration, resulting in dementia. In recent decades, therapeutic approaches have attempted to decrease the levels of abnormal Aβ or tau levels in the AD brain. However, several of these approaches have either been associated with an inappropriate immune response triggering inflammation, or have failed to improve cognition. Here, we review the pathogenesis and potential therapeutic targets associated with dysfunction of the NVU in AD.     

Insoluble Vascular Amyloid Deposits Trigger Disruption of the Neurovascular Unit in Alzheimer’s Disease Brains

Alzheimer’s disease (AD) is a neurodegenerative disease, characterized histopathologically by intra-neuronal tau-related lesions and by the accumulation of amyloid β-peptide (Aβ) in the brain parenchyma and around cerebral blood vessels. According to the vascular hypothesis of AD, an alteration in the neurovascular unit (NVU) could lead to Aβ vascular accumulation and promote neuronal dysfunction, accelerating neurodegeneration and dementia. To date, the effects of insoluble vascular Aβ deposits on the NVU and the blood–brain barrier (BBB) are unknown. In this study, we analyze different Aβ species and their association with the cells that make up the NVU. We evaluated post-mortem AD brain tissue. Multiple immunofluorescence assays were performed against different species of Aβ and the main elements that constitute the NVU. Our results showed that there are insoluble vascular deposits of both full-length and truncated Aβ species. Besides, insoluble aggregates are associated with a decrease in the phenotype of the cellular components that constitute the NVU and with BBB disruption. This approach could help identify new therapeutic targets against key molecules and receptors in the NVU that can prevent the accumulation of vascular fibrillar Aβ in AD.     

3‐D Printing and Development of Fluoropolymer Based Reactive Inks

Engineering reactive materials is an ever present goal in the energetics community. The desire is to have energetics configured in such a manner that performance is tailored and energy delivery can be targeted. Additive manufacturing (3‐D printing) is one area that could significantly improve our capabilities in this area, if adequate formulations are developed. In this paper, fluoropolymer based reactive inks are developed with micron (mAl) and nanoscale aluminum (nAl) serving, as the fuel at high solids loading (up to 67 wt%) and their viscosity required for 3‐D printing is detailed. For the pen‐type technique and valves used in this work, it is required to have viscosities on the order of 10⁴–10⁵ cP. For printed traces with apparent diameters under <500 μm, the combustion velocities for both micron and nano scale aluminum formulations, are approximately identical: 30 ± 3 versus 32 ± 2 mm s^?1, respectively. Further increasing the apparent diameter is shown to increase the combustion velocity in the case of the nanoscale aluminum formulation by four‐fold over that of the micron scale aluminum formulation, but it plateaus as it approaches an apparent diameter of 2 mm. The results suggest with proper architecture that tailorable combustion rates and energy delivery are feasible.

     

Application of Cognitive Techniques to Adaptive Routing for VANETs in City Environments

The evolution of smart vehicles has widened the application opportunities for vehicular ad hoc networks. In this context, the routing issue is still one of the main challenges regarding to the performance of the network. Although there are multiple ad hoc routing proposals, the traditional general-purpose approaches do not fit the distinctive properties of vehicular network environments. New routing strategies must complement the existing protocols to improve their performance in vehicular scenarios. This paper introduces a novel intelligent routing technique that makes decisions in order to adaptively adjust its operation and obtain a global benefit. The nodes sense the network locally and collect information to feed the cognitive module which will select the best routing strategy, without the need of additional protocol message dissemination or convergence mechanism.     

Dipeptidyl peptidase activities along the processing of Serrano dry-cured ham

The activity of pork muscle dipeptidyl peptidases I, II, III, and IV was followed during the processing of Serrano dry-cured ham. The effects of NaCl, pH, and temperature on these enzymes have also been studied for a better understanding of their importance in ham processing. The lysosomal enzymes DPP I and DPP II showed maximal activity at pH around 5.5-6.0, i.e., close to the pH in ham. At low temperatures, only DPP I and DPP IV showed relevant activity. NaCl considerably inhibited DPP activities except DPP I which was only slightly affected. Dipeptidyl peptidases remained active during the whole process except DPP II whose activity disappeared after 240 days of dry-curing.     

An enzyme sensor for the determination of total amines in dry-fermented sausages

An enzyme sensor employing diamine oxidase from porcine kidney in combination with an oxygen electrode has been developed and optimised to estimate the content of total amines in dry-fermented sausages. The enzyme DAO was immobilised on a preactivated Immunodyne membrane using glutaraldehyde as cross-linking agent. The enzymatic determination was based on the measurement of the consumed O₂ in a platinum electrode poised at −600 mV versus Ag/AgCl. The reaction was started by the direct injection of either the standard or meat extract on the enzymatic membrane. The immobilised enzyme could be used up to 30 analyses along the day without significant loss of sensitivity and could be stored at 4 °C showing good stability for at least 6 weeks. A good correlation was observed when comparing data obtained with the enzyme sensor to those obtained with a standard HPLC method. Thus, this sensor may be a reliable screening method to detect the presence of biogenic amines in dry-fermented sausages that can constitute a useful tool for quality control in the meat industry.     

Development of a dielectric spectroscopy technique for the determination of key biochemical markers of meat quality

Dielectric measurements of different standard solutions (nucleotides, nucleosides, lactic acid and myoglobin) were assayed simulating the concentrations of these substances in early postmortem meat. These assays were performed for considering the potential use of dielectric spectra for the quality control of meat. Good correlations among solutions of Adenosine Triphosphate (ATP), Inosine Monophosphate (IMP) and lactic acid with loss factor at punctual frequencies (0.5, 0.915 and 1 GHz) were found. The other assayed substances did not present a marked effect over the electromagnetic spectra. Good correlations of dielectric properties with IMP and lactic acid content of real pork meat samples were also found at 0.5 GHz. This work is presenting prospective data of dielectric spectra for certain key biochemical markers in order to consider its potential application as a non-destructive control sensor for the prediction of pork meat quality.