Insights into Alzheimer disease pathogenesis from studies in transgenic animal models

Alzheimer disease is the most common cause of dementia among the elderly, accounting for ∼60-70% of all cases of dementia. The neuropathological hallmarks of Alzheimer disease are senile plaques (mainly containing β-amyloid peptide derived from amyloid precursor protein) and neurofibrillary tangles (containing hyperphosphorylated Tau protein), along with neuronal loss. At present there is no effective treatment for Alzheimer disease. Given the prevalence and poor prognosis of the disease, the development of animal models has been a research priority to understand pathogenic mechanisms and to test therapeutic strategies. Most cases of Alzheimer disease occur sporadically in people over 65 years old, and are not genetically inherited. Roughly 5% of patients with Alzheimer disease have familial Alzheimer disease—that is, related to a genetic predisposition, including mutations in the amyloid precursor protein, presenilin 1, and presenilin 2 genes. The discovery of genes for familial Alzheimer disease has allowed transgenic models to be generated through the overexpression of the amyloid precursor protein and/or presenilins harboring one or several mutations found in familial Alzheimer disease. Although none of these models fully replicates the human disease, they have provided valuable insights into disease mechanisms as well as opportunities to test therapeutic approaches. This review describes the main transgenic mouse models of Alzheimer disease which have been adopted in Alzheimer disease research, and discusses the insights into Alzheimer disease pathogenesis from studies in such models. In summary, the Alzheimer disease mouse models have been the key to understanding the roles of soluble β-amyloid oligomers in disease pathogenesis, as well as of the relationship between β-amyloid and Tau pathologies

What is a Gene? A Two Sided View

The need to account for all currently available experimental observations concerning the gene nature, has reshaped the concept of gene turning it from the essentially mechanistic unit, predominant during the '70s, into a quite abstract open and generalized entity, whose contour appears less defined as compared to the past. Here we propose the essence of the gene to be considered double faced. In this respect genotypic and phenotypic entities of a gene would coexist and mix reciprocally. This harmonizes present knowledge with current definitions and predisposes for remodelling of our thinking as a consequence of future discoveries. A two sided view of the gene also allows to combine the genetic and epigenetic aspects in a unique solution, being structural and functional at the same time and simultaneously able to include the different levels in an overlapping unicum

A Very Early "fashion": Neolithic Stone Bracelets from a Mediterranean Perspective

Ring-shaped objects, used mainly as bracelets, appear in the archaeological record associated with the first farming societies around the Mediterranean area. These bracelets, among other personal ornaments, are related to the spread of the farming economy in the Mediterranean (10th-6th millennium BC). In particular, stone bracelets, given their intricate technology, are linked with the early stages of craft specialization and the beginnings of complex social organization. Likewise, their frequency in Early Neolithic assemblages and the lithologies in which they were made have become an important element in the study of the circulation networks of goods, as well as the symbolic behaviors and aesthetic preferences of the first farming groups. This research provides the first overview of the stone bracelets of Neolithic groups in the Mediterranean. We compare the similarities and differences among these ornaments in different geographical zones across the region including Turkey, Greece, Italy, and Spain. Using all the information available about these ornaments - chronology, typology, raw materials and manufacturing processes, use-wear, repair, and alteration practices - we shed light on a complex archaeological trans-cultural manifestation related to the spread of the Neolithic lifestyle across the European continent

Electrochemical biosensors based on nanomodified screen-printed electrodes: Recent applications in clinical analysis

This review addresses recent advances in the development of screen-printed electrode based biosensors modified with different nanomaterials such as carbon nanotubes, graphene, metallic nanoparticles as gold, silver and magnetic nanoparticles, and mediator nanoparticles (Prussian Blue, Cobalt Phthalocyanine, etc.), coupled with biological recognition elements such as enzymes, antibodies, DNA and aptamers to obtain probes with improved analytical features. Examples of clinical applications are illustrated, together with examples of paper-based electrochemical devices, of multiple detections using arrays of screen printed electrodes, and of the most recent developments in the field of wearable biosensors. Also the use of smartphones as final detectors is briefly depicted. © 2016 Elsevier B.V

Polarization entangled photon-pair source based on quantum nonlinear photonics and interferometry

We present a versatile, high-brightness, guided-wave source of polarization entangled photons, emitted at a telecom wavelength. Photon-pairs are generated using an integrated type-0 nonlinear waveguide, and subsequently prepared in a polarization entangled state via a stabilized fiber interferometer. We show that the single photon emission wavelength can be tuned over more than 50 nm, whereas the single photon spectral bandwidth can be chosen at will over more than five orders of magnitude (from 25 MHz to 4 THz). Moreover, by performing entanglement analysis, we demonstrate a high degree of control of the quantum state via the violation of the Bell inequalities by more than 40 standard deviations. This makes this scheme suitable for a wide range of quantum optics experiments, ranging from fundamental research to quantum information applications. We report on details of the setup, as well as on the characterization of all included components, previously outlined in F. Kaiser et al. (2013 Laser Phys. Lett. 10, 045202).Comment: 16 pages, 7 figure

COMBUSTION ANALYSIS OF D-LIMONENE AS AN ADDITIVE TO DIESEL-BIODIESEL BLENDS IN COMPRESSION IGNITION ENGINES

Vegetable oils, when subjected to transesterification process generate “vegetable oils esters”, with similar properties as density, cetane number, heating values, air-fuel ratio. However, problems resulting from the higher viscosity, leads to a worst spraying and combustion, formation of undesirable deposits on engine parts and contamination of the lubricant oil. Due to these problems, it is interesting to study an additive, also derived from biomass, to improve the characteristics of biodiesel for a suitable use in diesel engines. This paper proposes an additive (d-limonene obtained from orange peel) and preliminary results obtained from the tests in a stationary diesel engine fueled with mixtures of diesel/biodiesel/d-limonene, in different concentration to compare with a regular diesel-biodiesel blend and analyzes the influence of the additive on the combustion process. The diesel oil used was purchased from BR supply network (containing 7% biodiesel in its composition) and two blends with different concentrations of the additive (1% and 3% of d-limonene) were prepared and tested. Diesel without additive was also tested. The effects of the DS10 addititivation with d-limonene in the combustion process of a diesel engine have been analyzed, the results obtained were satisfactory showing the positive effects in the combustion process with the addition of d-limonene in diesel-biodiesel blends, decreasing the ignition delay around 2 degrees and showing an improvement in the cetane number of the fuel

The active second-generation proteasome inhibitor oprozomib reverts the oxaliplatin-induced neuropathy symptoms

Oxaliplatin-induced neuropathy (OXAIN) is a major adverse effect of this antineoplastic drug, widely used in the treatment of colorectal cancer. Although its molecular mechanisms remain poorly understood, recent evidence suggest that maladaptive neuroplasticity and oxidative stress may participate to the development of this neuropathy. Given the role played on protein remodeling by ubiquitin–proteasome system (UPS) in response to oxidative stress and in neuropathic pain, we investigated whether oxaliplatin might cause alterations in the UPS-mediated degradation pathway, in order to identify new pharmacological tools useful in OXAIN. In a rat model of OXAIN (2.4 mg kg−1 i.p., daily for 10 days), a significant increase in chymotrypsin-(β5) like activity of the constitutive proteasome 26S was observed in the thalamus (TH) and somatosensory cortex (SSCx). In addition, the selective up-regulation of β5 and LMP7 (β5i) subunit gene expression was assessed in the SSCx. Furthermore, this study revealed that oprozomib, a selective β5 subunit proteasome inhibitor, is able to normalize the spinal prodynorphin gene expression upregulation induced by oxaliplatin, as well as to revert mechanical allodynia and thermal hyperalgesia observed in oxaliplatin-treated rats. These results underline the relevant role of UPS in the OXAIN and suggest new pharmacological targets to counteract this severe adverse effect. This preclinical study reveals the involvement of the proteasome in the oxaliplatin-induced neuropathy and adds useful information to better understand the molecular mechanism underlying this pain condition. Moreover, although further evidence is required, these findings suggest that oprozomib could be a therapeutic option to counteract chemotherapy-induced neuropathy