57,070 research outputs found
Phase Diagram of Aqueous Solutions of LiCl: a Study of Concentration Effects on the Anomalies of Water
No full textWe perform molecular dynamics simulationsin order tostudy thermodynamicsand the structure of supercooled aqueous solutions of lithium chloride(LiCl) at concentrations c = 0.678 and 2.034 mol/kg.We model the solvent using the TIP4P/2005 potential and the ions usingthe Madrid-2019 force field, a force field particularly suited forstudying this solution. We find that, for c = 0.678mol/kg, the behavior of the equation of state, studied in the P-T plane, indicates the presenceof a liquid-liquid phase transition, similar to what was previouslyfound for bulk water. We estimate the position of the liquid-liquidcritical point to be at T (c) approximate to 174K, P (c) approximate to 1775 bar, and rho(c) approximate to 1.065 g/cm(3). When the concentration istripled to c = 2.034 mol/kg, no critical point isobserved, indicating its possible disappearance at this concentration.We also study the water-water and water-ions structurein the two solutions, and we find that at the concentrations examinedthe effect of ions on the water-water structure is not strong,and all the features found in bulk water are preserved. We also calculatethe hydration number of the Li and Cl ions, and in line with experiments,we find the value of 4 for Li+ and between 5.5 and 6 forCl(-), confirming the good performances of the Madrid-2019force field
The vestibular hair cells: post-transductional signal processing.
No full textHair cells in mechanosensory systems transduce mechanical stimuli into biological signals to be presented to and analyzed by the brain. Vestibular hair cells transduce stimuli primarily associated with the organism's orientation and motion in space. When examined superficially it may appear that the hair cells act as passive transducers whereby mechanical stimulation of their hair bundle results in transmitter release at their afferent synapses. In fact, hair cell functions are more complicated, and the mechanical signals are heavily processed even before being encoded in afferent nerve activity. Hair cells are different from one another in morphology, biophysics, transmitter and transmitter receptor complements, not only across different organs (as one might expect), but even in the same organ. This review focuses on hair cell morpho-physiological properties, ionic conductances, neurotransmitters/modulators and their receptors, second messengers and effectors. Special features of hair cell neurotransmission, as the synaptic body and the presence of autoreceptors and local circuits, are also discussed, as is the possibility of a differential modulation of hair cell transmitter release in the resting and mechanically-stimulated states
Isolation and characterisation of mouse intestinal mesoangioblasts
No full textAIMS AND OBJECTIVES: Children suffering from intestinal failure (IF) endure considerable morbidity and overall have poor survival rates, complicated by the shortage of organs available for transplantation. Therefore, new therapeutic approaches are pivotal if outcomes are to be improved. Over the past years, tissue engineering (TE) has emerged as a possible alternative treatment for many congenital and acquired conditions. TE aims at creating bioengineered organs by means of combining scaffolds with appropriate cell types, which in the intestine are organised within a multilayer structure. In order to generate functional intestine, this cellular diversity and organisation will need to be recreated. While the cells for the epithelial, neural and vascular compartments have been well defined, so far, less attention has been put on the muscular compartment. More recently, mesoangioblasts (MABs) have been identified as a novel source for tissue regeneration since they are able to give rise to vascular and other mesodermal derivatives. To date MABs have not been successfully isolated from intestinal tissue. Therefore, our aim was to demonstrate the possibility of isolating MABs from adult mouse small intestine. MATERIALS AND METHODS: All experiments were carried out using small intestinal tissues from C57BL/6J mice. We applied an established protocol for MAB isolation from the isolated neuromuscular layer of the small intestine. Cultured cells were stained for Ki67 to assess proliferation rates as well as for a panel of pericyte markers to determine their phenotype. RESULTS: Cells were successfully isolated from gut biopsies. Cultured cells showed good proliferative capacity and positivity for at least three pericytes markers found in vessels of the gut neuromuscular wall: neuron-glial antigen 2, alkaline phosphatase and platelet-derived growth factor β. CONCLUSION: This proof-of-principle study lays the foundation for further characterization of MABs as a possible cell source for intestinal smooth muscle regeneration and TE.sponsorship: The authors would like to acknowledge the NIHR Great Ormond Street Hospital Biomedical Research Centre which supports all research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Additional support for this project was provided by Horizon 2020 INTENS funding. NT is supported by Great Ormond Street Hospital Children's Charity. SP's PhD studentship is funded through a GOSHCC grant awarded to NT. CM is supported by Guts UK (Derek Butler Fellowship). PDC is supported by National Institute for Health Research (NIHR-RP-2014-04-046). (NIHR Great Ormond Street Hospital Biomedical Research Centre, Horizon 2020 INTENS funding, Great Ormond Street Hospital Children's Charity, GOSHCC, Guts UK (Derek Butler Fellowship), National Institute for Health Research|NIHR-RP-2014-04-046)status: Publishe
Measurement of the ratio of prompt χ c to J / ψ production in pp collisions at √s = 7 TeV
No full textThe prompt production of charmonium χ c and J / ψ states is studied in proton-proton collisions at a centre-of-mass energy of √s = 7 TeV at the Large Hadron Collider. The χ c and J / ψ mesons are identified through their decays χ c → J / ψ γ and J / ψ → μ + μ - using 36 pb - 1 of data collected by the LHCb detector in 2010. The ratio of the prompt production cross-sections for χ c and J / ψ, σ (χ c → J / ψ γ) / σ (J / ψ), is determined as a function of the J / ψ transverse momentum in the range 2 < p T J / ψ < 15 GeV / c. The results are in excellent agreement with next-to-leading order non-relativistic expectations and show a significant discrepancy compared with the colour singlet model prediction at leading order, especially in the low p T J / ψ region
A comparison of the cholinergic properties of the leopard frog utricle, saccule and semicircular canals.
No full textInsulin secretion and hepatic insulin clearance as determinants of hyperinsulinaemia in normotolerant grossly obese adolescents
No full textObesity is characterized by variable degrees of hyperinsulinaemia, which has been attributed to either beta-cell hypersecretion or reduced hepatic insulin extraction, or both. To investigate this controversial issue, a 4-h frequently sampled i.v. glucose tolerance test (glucose dose 12.8 g m(-2)) was performed in 13 normotolerant, grossly obese adolescents (10 F/3 M; 13 +/- 1 y; body mass index 32 +/- 0.9; pubertal stage 4-5; obesity duration 7.8 +/- 3 y) and in a comparable group of 8 healthy, normal-weight subjects. Glucose, insulin and C-peptide time-course were analysed by the minimal model technique, which estimates beta-cell secretion, insulin sensitivity (S-i), glucose effectiveness (S-G) and hepatic insulin extraction (HE). Despite similar fasting and after load glucose patterns (S-G similar in the two groups), obese adolescents showed sustained peripheral hyperinsulinaemia (total insulin area under the concentration curve 67.2 +/- 10.8 vs 19.1 +/- 1.2 pmol l(-1) in 240 min; p < 0.002) and a 71% reduction in Si (2.02 +/- 0.33 vs 6.95 +/- 1.03 x 10(4) min(-1) (mu U ml(-1)); p < 0.001), Compared with control subjects, the total amounts of prehepatic insulin secretion and posthepatic insulin delivery were also increased significantly in obese adolescents by 30% and 46%, respectively; HE was reduced by 15% during the first 30 min of the test, but recovered within the normal range during the rest of the test. In conclusion, severely obese adolescents are insulin resistant and their hyperinsulinaemia is primarily caused by beta-cell hypersecretion, whereas the reduction in insulin hepatic extraction is a transient metabolic phenomenon
Alport syndrome from bench to bedside: the potential of current treatment beyond RAAS blockade and the horizon of future therapies
No full text<p>The hereditary type IV collagen disease Alport syndrome (AS) always leads to end-stage renal failure. Yesterday, for the past 90 years, this course was described as 'inevitable'. Today, RAAS blockade has changed the 'inevitable' course to a treatable disease. Tomorrow, researchers hope to erase the 'always' from '<i>always</i> leads to renal failure' in the textbooks. This review elucidates therapeutic targets that evolve from research: (i) kidney embryogenesis and pathogenesis; (ii) phenotype-genotype correlation and the role of collagen receptors and podocytes; (iii) the malfunctioning Alport-GBM; (iv) tubulointerstitial fibrosis; (v) the role of proteinuria in pathogenesis and prognosis; and (vi) secondary events such as infections, hyperparathyroidism and hypercholesterolaemia. Therefore, moderate lifestyle, therapy of bacterial infections, Paricalcitol in adult patients with hyperparathyroidism and HMG-CoA-reductase inhibitors in adult patients with dyslipoproteinemia might contribute to a slower progression of AS and less cardiovascular events. In the future, upcoming treatments including stem cells, chaperon therapy, collagen receptor blockade and anti-microRNA therapy will expand our perspective in protecting the kidneys of Alport patients from further damage. This perspective on current and future therapies is naturally limited by our personal focus in research, but aims to motivate young scientists and clinicians to find a multimodal cure for AS.</p>
Immunohistochemical evaluation of multiple biological markers in ductal carcinoma in situ of the breast
No full textIn order to obtain prognostic clinicopathological information, 49 cases of pure ductal carcinoma in situ of the breast (DCIS), were evaluated for the immunohistochemical expression of potential predictor markers including c-erbB-2 oncogene product, p53 protein, oestrogen (ER) and progesterone (PR) receptors, oestrogen-regulated proteins pS2 and cathepsin-D (cath-D), CD44 protein and 67-kDa laminin receptor (MLuC5). Immunohistochemical findings were compared with conventional pathological parameters, clinical findings, and the clinical outcome of the patients. When markers were matched to each other, statistical analyses provided a significant positive correlation between c-erbB-2 overexpression and p53 positivity (P < 0.01) and between ER and PR (P < 0.01), ER, PR and pS2 (P < 0.01), pS2 and MLuC5 (P < 0.05). Significant negative correlations between c-erbB-2 overexpression and ER (P < 0.05), PR (P < 0.01) and pS2 (P < 0.01) positivity was also observed. Data on the relationship between marker status and pathological findings revealed a significant positive trend between c-erbB-2, p53, and increased grade values (P < 0.05) and opposite results with SR receptor expression (P < 0.01). c-erbB-2 overexpression was further significantly associated with comedotype carcinoma (P < 0.05) and distribution of disease in confluent neoplastic ducts (P < 0.01). Although no statistically significant correlation among biological markers expression, clinical findings and outcome was demonstrated, overall this study indicates that tumour cells from a subset of DCIS, which includes comedotype carcinoma, express significantly unfavourable prognostic factors. Copyright (C) 1996 Elsevier Science Lt
Mechanisms and effects of transepithelial polarization in the isolated semicircular canal.
No full textPrevious studies have shown that galvanic stimulation of semicircular canal organs can modulate their afferent discharge. However, it has not been resolved whether this modulation derived from direct stimulation of hair cells, afferent nerve fibers, some combination of the two, or some as yet unknown path. This problem is addressed in the present study. Experiments were designed first to determine the gross current path necessary for the DC current to modulate afferent firing. These led to the conclusion that the current path had to flow between endolymph and perilymph across the neuroepithelium. Next, the various components in this established path were considered: the afferents, the hair cells, between the hair cells, or some combination of the three. These experiments led to the conclusion that the current pathway was across the hair cells causing transmitter release and thus affecting afferent activity
Hemodynamic evaluation of cerebral vasomotor reactivity in juvenile migraine patients: a transcranial Doppler-study.
No full text- …
