Identifying a putative common binding site shared by substance P receptor and an anti-substance P monoclonal antibody

Substance P G-protein coupled receptor and the antigen recognitionsite of a monoclonal antibody raised against substance P sharea stretch of five contiguous identical amino acids. This observationprompted us to build an atomic model of both the receptor andthe antibody and to analyse their common features. In particular,we report here that a pocket of similar size and compositionis present in both proteins, strongly suggesting a similarityin the mode of binding of both macromolecules to substance P.From the analysis of our models, the available data on the modeof binding of the antibody to substance P and recent data onsubstance P receptor mutants, we concluded that the pocket isvery likely to be involved in binding of the C-terminal 'messagesequence' of the tachykinin. This allowed us to suggest specificsite-directed mutants of the receptor which should shed somelight on the mechanism of peptide recognition by G-protein coupledreceptors.     

A comparison between wet and cryogenic drilling of CFRP/Ti stacks

This paper compares conventional and cryogenic cooling in the deep hole drilling of carbon fiber reinforced polymer (CFRP)/Ti stacks. Various parameters are taken into account to find if the use of cryogenic coolant is justified by the improvement of the final results. Both the thrust and the torque were acquired continuously during the machining operations and compared both in average and distribution. The use of a cryogenic coolant brings a reduction in thrust force and torque without any sensible drawback. Overall the results prove that cryogenic drilling is a suitable technology for CFRP/Ti stack drill.     

A theoretical analysis of the influence of fixational instability on the development of thalamocortical connectivity

Under natural viewing conditions, the physiological instability of visual fixation keeps the projection of the stimulus on the retina in constant motion. After eye opening, chronic exposure to a constantly moving retinal image might influence the experience-dependent refinement of cell response characteristics. The results of previous modeling studies have suggested a contribution of fixational instability to the Hebbian maturation of the receptive fields of V1 simple cells (Rucci, Edelman, & Wray, 2000; Rucci & Casile, 2004). This letter examines the origins of such a contribution. Using quasilinear models of lateral geniculate nucleus units and V1 simple cells, we derive analytical expressions for the second-order statistics of thalamocortical activity before and after eye opening. We show that in the presence of natural stimulation, fixational instability introduces a spatially uncorrelated signal in the retinal input, which strongly influences the structure of correlated activity in the model. This input signal produces a regime of thalamocortical activity similar to that present before eye opening and compatible with the Hebbian maturation of cortical receptive fields.     

Geometry and Stacking Sequence Effect on Composite Spinnaker Pole's Stiffness: Experimental and Numerical Analysis

Composite materials are widely employed in sailing sports, a possible application is for the mast pole or other sail poles. In the paper the attention is focused on the spinnaker poles mechanical performances; in particular the focus is on axial and ring compressive properties of three different carbon fibre/epoxy resin spinnaker poles, to investigate both the diameter and stacking sequence effect on the mechanical performance of the structure. Starting from the stacking sequence used in the production of a particular spinnaker pole, the effect of a lamina at 0° in the middle of wall thickness is investigated with the purpose to obtain a more stiff structure. Moreover to test the proposed stacking sequence on different size products, a prototype with lower diameter is realized. To properly evaluate axial and ring stiffness, axial compression test and ring stiffness one are performed. Then a numerical model is developed to support the design of the finished product: A simple and versatile numerical analysis (FEA with software ANSYS), by simulating ring stiffness and pull-direction compression tests, is carried out in elastic regime. Such model should be suitable for designing and/or verifying the mechanical performance of pole structures, even though differing from those above described, for materials, geometry and stacking sequence.     

Roles of Notch Signaling in the Tumor Microenvironment

The Notch signaling pathway is an architecturally simple signaling mechanism, well known for its role in cell fate regulation during organ development and in tissue homeostasis. In keeping with its importance for normal development, dysregulation of Notch signaling is increasingly associated with different types of tumors, and proteins in the Notch signaling pathway can act as oncogenes or tumor suppressors, depending on the cellular context and tumor type. In addition to a role as a driver of tumor initiation and progression in the tumor cells carrying oncogenic mutations, it is an emerging realization that Notch signaling also plays a role in non-mutated cells in the tumor microenvironment. In this review, we discuss how aberrant Notch signaling can affect three types of cells in the tumor stroma—cancer-associated fibroblasts, immune cells and vascular cells—and how this influences their interactions with the tumor cells. Insights into the roles of Notch in cells of the tumor environment and the impact on tumor-stroma interactions will lead to a deeper understanding of Notch signaling in cancer and inspire new strategies for Notch-based tumor therapy.     

Molecular Effects of Chronic Exposure to Palmitate in Intestinal Organoids: A New Model to Study Obesity and Diabetes

Intestinal cell dysfunctions involved in obesity and associated diabetes could be correlated with impaired intestinal cell development. To date, the molecular mechanisms underlying these dysfunctions have been poorly investigated because of the lack of a good model for studying obesity. The main aim of this study was to investigate the effects of lipotoxicity on intestinal cell differentiation in small intestinal organoid platforms, which are used to analyze the regulation of cell differentiation. Mouse intestinal organoids were grown in the presence/absence of high palmitate concentrations (0.5 mM) for 48 h to simulate lipotoxicity. Palmitate treatment altered the expression of markers involved in the differentiation of enterocytes and goblet cells in the early (Hes1) and late (Muc2) phases of their development, respectively, and it modified enterocytes and goblet cell numbers. Furthermore, the expression of enteroendocrine cell progenitors (Ngn3) and I cells (CCK) markers was also impaired, as well as CCK-positive cell numbers and CCK secretion. Our data indicate, for the first time, that lipotoxicity simultaneously influences the differentiation of specific intestinal cell types in the gut: enterocytes, goblet cells and CCK cells. Through this study, we identified novel targets associated with molecular mechanisms affected by lipotoxicity that could be important for obesity and diabetes therapy.     

Effect of Vacuum and Modified Atmosphere Packaging on the Shelf-life of Liquid-smoked Swordfish (Xiphias gladius) Slices

ABSTRACT: Swordfish fillets, dry-salted and treated with liquid smoke, were sliced and packed in vacuum conditions and under modified atmosphere (MA) (5% O₂,45% CO₂, 50% N₂) and stored at chilled temperature (4°C) to determine the effect of different packaging on shelf-life. Sensory attributes, total volatile basic nitrogen (TVB-N), pH, lipid oxidation by thiobarbituric acid test, and microbiological counts were monitored during 45 d of storage. The TVB-N increased to levels recommended by European regulation at the time of sensory rejection, resulting as the most reliable parameter of quality decay. Lipid oxidation was low and microbial counts could not be correlated with quality decay. Sensory rejection (at least 50% of the assessors scoring =5 in a scale from 1 to 9) was sooner for MA-packed samples (12d) than for vacuum-packed ones (42d).     

Pathogenetic Mechanisms of Hypertension–Brain-Induced Complications: Focus on Molecular Mediators

There is growing evidence that hypertension is the most important vascular risk factor for the development and progression of cardiovascular and cerebrovascular diseases. The brain is an early target of hypertension-induced organ damage and may manifest as stroke, subclinical cerebrovascular abnormalities and cognitive decline. The pathophysiological mechanisms of these harmful effects remain to be completely clarified. Hypertension is well known to alter the structure and function of cerebral blood vessels not only through its haemodynamics effects but also for its relationships with endothelial dysfunction, oxidative stress and inflammation. In the last several years, new possible mechanisms have been suggested to recognize the molecular basis of these pathological events. Accordingly, this review summarizes the factors involved in hypertension-induced brain complications, such as haemodynamic factors, endothelial dysfunction and oxidative stress, inflammation and intervention of innate immune system, with particular regard to the role of Toll-like receptors that have to be considered dominant components of the innate immune system. The complete definition of their prognostic role in the development and progression of hypertensive brain damage will be of great help in the identification of new markers of vascular damage and the implementation of innovative targeted therapeutic strategies.     

The BDNF/TrkB Neurotrophin System in the Sensory Organs of Zebrafish

The brain-derived neurotrophic factor (BDNF) was discovered in the last century, and identified as a member of the neurotrophin family. BDNF shares approximately 50% of its amino acid with other neurotrophins such as NGF, NT-3 and NT-4/5, and its linear amino acid sequences in zebrafish (Danio rerio) and human are 91% identical. BDNF functions can be mediated by two categories of receptors: p75NTR and Trk. Intriguingly, BDNF receptors were highly conserved in the process of evolution, as were the other NTs’ receptors. In this review, we update current knowledge about the distribution and functions of the BDNF-TrkB system in the sensory organs of zebrafish. In fish, particularly in zebrafish, the distribution and functions of BDNF and TrkB in the brain have been widely studied. Both components of the system, associated or segregated, are also present outside the central nervous system, especially in sensory organs including the inner ear, lateral line system, retina, taste buds and olfactory epithelium.