Collagen remnants in ancient bone

Ancient bone collagen retains valuable information. Radiocarbon dating, thermal dating, species identification, cladistics analyses, and paleodietary reconstruction efforts all use bone collagen from ancient samples. Experimentally derived models of the temperature-dependent collagen half-life and thus of collagen’s expected shelf life under optimum preservation conditions currently stand at odds with literature reports of collagen remnants in bones with great apparent ages. These issues cause debate about bone collagen longevity. The situation highlights a need to better understand bone collagen preservation conditions and thus to apply new analytical tools to ancient and modern bone samples. In response, this study applies established techniques to ancient bone for the first time. Appropriate samples of ancient bone were first collected and catalogued. They include specimens ranging from Medieval to Paleozoic settings and involve partnerships with six permanent repositories. This thesis describes the novel application of second-harmonic generation (SHG) imaging, an established technique in biomedical science, to ancient bone. In this study, four separate and independent techniques confirmed that SHG reliably detects trace amounts of collagen protein in certain Medieval and Ice Age bone samples. Additional results indicate that SHG detects faint traces of collagen in unexpectedly old bone samples, including dinosaur bones. The technique demonstrated a high degree of sensitivity to small amounts of collagen, plus the potential to explore the micromorphology of collagen decay in bone and other collagenous tissues. The second novel application was Fourier-transform infrared (FTIR) spectroscopy. Recent studies demonstrated its usefulness for bone collagen content estimates in forensic analyses of bone remains. This study extended its application to Medieval, Ice Age, Cretaceous, Jurassic, and Devonian samples and found a general trend of diminishing collagen signal with older bones. FTIR was also used for the first time to assess bone collagen integrity in an artificial decay experiment. In addition, the applicability of Raman spectroscopy to ancient bone was explored. Accelerator mass spectrometry (AMS) was also used to measure stable and unstable carbon ratios in many of the same ancient bone samples used above. AMS 13C results brought forth two main conclusions. They confirmed the accuracy of preliminary results obtained using a recently developed portable quadrupole mass spectrometer (QMS) to detect stable isotopes including 13C and 12C ratios from the bioapatite fraction of Medieval bone. They also confirm for the first time a co-occurrence of primary (i.e., original to the organism) isotopic signatures in fossil bones with primary organic signatures. Analysis of published Cretaceous vertebrate fossils with biological stable isotope ratios matched this co-occurrence. Finally, the first AMS 14C results from Cretaceous bone collagen are presented. 14C results discriminated between modern, medieval, Roman era, and ice age, but not between Cretaceous and Jurassic time frames. Overall results suggest that the application of novel techniques like SHG will help detect and further characterise ancient bone collagen. Also, low cost, nearly nondestructive tools like FTIR and QMS show promise to aid continued discoveries of original isotope ratios and biological remnants like bone collagen in fossils from widening geographic and geological ranges

Point-Coupling Models from Mesonic Hypermassive Limit and Mean-Field Approaches

In this work we show how nonlinear point-coupling models, described by a Lagrangian density that presents only terms up to fourth order in the fermion condensate $(\bar{\psi}\psi)$, are derived from a modified meson-exchange nonlinear Walecka model. The derivation can be done through two distinct methods, namely, the hypermassive meson limit within a functional integral approach, and the mean-field approximation in which equations of state at zero temperature of the nonlinear point-coupling models are directly obtained.Comment: 18 pages. Accepted for publication in Braz. J. Phy

The influence of liver dysfunction on cyclosporine pharmacokinetics -A comparison between 70 per cent hepatectomy and complete bile duct ligation in dogs-

The influence of experimentally induced hepatic dysfunction on the pharmacokinetics of Cyclosporine A (CsA) was determined in dogs. The pharmacokinetics of oral (PO) and intravenous (IV) CsA were studied before and after 70 per cent hepatectomy or complete bile duct ligation (CBDL). Changes in liver function were monitored by serial measurements of serum bilirubin, and by the maximum removal rate (Rmax) and plasma disappearance rate (ICG-K) of indocyanine green (ICG). Concentrations of CsA in whole blood were measured by HPLC. Seventy per cent hepatectomy caused significant liver dysfunction: the ICG-Rmax decreased by 47.7±7.1 per cent (mean±SD) and the ICG-K decreased by 61.3±9.7 per cent during the first week after hepatectomy. At the same time, the systemic clearance (CLs) of IV-CsA decreased by 43.9±8.2 per cent, the area under the concentration curve (AUC) of IV-CsA increased by 35.4±20.8 per cent and the bioavailability of CsA decreased by 26.4±14.8 per cent. CBDL also induced significant liver dysfunction: the ICG-Rmax decreased by 39.1±12.8 per cent and the ICG-K decreased by 65.6±3.6 per cent in the second week after the operation. During the same period, the AUC of PO-CsA decreased by 69.9±10.7 per cent and the bioavailability of CsA also decreased markedly by 73.9±15.6 per cent. These data indicate that hepatic impairment significantly influences the pharmacokinetics of CsA, not only by the changes in intestinal absorption, but also by those in hepatic, metabolism. Dose adjustment is therefore necessary in the presence of hepatic dysfunction in order to maintain an adequate blood concentration of CsA without causing side effects. © 1989 The Japan Surgical Society

Double In Situ Approach for the Preparation of Polymer Nanocomposite with Multi-functionality

A novel one-step synthetic route, the double in situ approach, is used to produce both TiO2nanoparticles and polymer (PET), and simultaneously forming a nanocomposite with multi-functionality. The method uses the release of water during esterification to hydrolyze titanium (IV) butoxide (Ti(OBu)4) forming nano-TiO2in the polymerization vessel. This new approach is of general significance in the preparation of polymer nanocomposites, and will lead to a new route in the synthesis of multi-functional polymer nanocomposites

Carboxyhaemoglobin levels and their determinants in older British men

Background: Although there has been concern about the levels of carbon monoxide exposure, particularly among older people, little is known about COHb levels and their determinants in the general population. We examined these issues in a study of older British men.Methods: Cross-sectional study of 4252 men aged 60-79 years selected from one socially representative general practice in each of 24 British towns and who attended for examination between 1998 and 2000. Blood samples were measured for COHb and information on social, household and individual factors assessed by questionnaire. Analyses were based on 3603 men measured in or close to (< 10 miles) their place of residence.Results: The COHb distribution was positively skewed. Geometric mean COHb level was 0.46% and the median 0.50%; 9.2% of men had a COHb level of 2.5% or more and 0.1% of subjects had a level of 7.5% or more. Factors which were independently related to mean COHb level included season (highest in autumn and winter), region (highest in Northern England), gas cooking (slight increase) and central heating (slight decrease) and active smoking, the strongest determinant. Mean COHb levels were more than ten times greater in men smoking more than 20 cigarettes a day (3.29%) compared with non-smokers (0.32%); almost all subjects with COHb levels of 2.5% and above were smokers (93%). Pipe and cigar smoking was associated with more modest increases in COHb level. Passive cigarette smoking exposure had no independent association with COHb after adjustment for other factors. Active smoking accounted for 41% of variance in COHb level and all factors together for 47%.Conclusion: An appreciable proportion of men have COHb levels of 2.5% or more at which symptomatic effects may occur, though very high levels are uncommon. The results confirm that smoking (particularly cigarette smoking) is the dominant influence on COHb levels

Plasma metabolites distinguish dementia with Lewy bodies from Alzheimer’s disease: a cross-sectional metabolomic analysis

Copyright \ua9 2024 Pan, Donaghy, Roberts, Chouliaras, O’Brien, Thomas, Heslegrave, Zetterberg, McGuinness, Passmore, Green and Kane.Background: In multifactorial diseases, alterations in the concentration of metabolites can identify novel pathological mechanisms at the intersection between genetic and environmental influences. This study aimed to profile the plasma metabolome of patients with dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD), two neurodegenerative disorders for which our understanding of the pathophysiology is incomplete. In the clinical setting, DLB is often mistaken for AD, highlighting a need for accurate diagnostic biomarkers. We therefore also aimed to determine the overlapping and differentiating metabolite patterns associated with each and establish whether identification of these patterns could be leveraged as biomarkers to support clinical diagnosis. Methods: A panel of 630 metabolites (Biocrates MxP Quant 500) and a further 232 metabolism indicators (biologically informative sums and ratios calculated from measured metabolites, each indicative for a specific pathway or synthesis; MetaboINDICATOR) were analyzed in plasma from patients with probable DLB (n = 15; age 77.6 \ub1 8.2 years), probable AD (n = 15; 76.1 \ub1 6.4 years), and age-matched cognitively healthy controls (HC; n = 15; 75.2 \ub1 6.9 years). Metabolites were quantified using a reversed-phase ultra-performance liquid chromatography column and triple-quadrupole mass spectrometer in multiple reaction monitoring (MRM) mode, or by using flow injection analysis in MRM mode. Data underwent multivariate (PCA analysis), univariate and receiving operator characteristic (ROC) analysis. Metabolite data were also correlated (Spearman r) with the collected clinical neuroimaging and protein biomarker data. Results: The PCA plot separated DLB, AD and HC groups (R2 = 0.518, Q2 = 0.348). Significant alterations in 17 detected metabolite parameters were identified (q ≤ 0.05), including neurotransmitters, amino acids and glycerophospholipids. Glutamine (Glu; q = 0.045) concentrations and indicators of sphingomyelin hydroxylation (q = 0.039) distinguished AD and DLB, and these significantly correlated with semi-quantitative measurement of cardiac sympathetic denervation. The most promising biomarker differentiating AD from DLB was Glu:lysophosphatidylcholine (lysoPC a 24:0) ratio (AUC = 0.92; 95%CI 0.809–0.996; sensitivity = 0.90; specificity = 0.90). Discussion: Several plasma metabolomic aberrations are shared by both DLB and AD, but a rise in plasma glutamine was specific to DLB. When measured against plasma lysoPC a C24:0, glutamine could differentiate DLB from AD, and the reproducibility of this biomarker should be investigated in larger cohorts

Fewer COVID-19 neurological complications with dexamethasone and remdesivir

OBJECTIVE: To assess the impact of treatment with dexamethasone, remdesivir or both on neurological complications in acute COVID-19. METHODS: We used observational data from the International Severe Acute and emerging Respiratory Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK). Hospital inpatients aged ≥18 years with laboratory-confirmed SARS-CoV-2 infection admitted between 31 January 2020 and 29 June 2021 were included. Treatment allocation was non-blinded and performed by reporting clinicians. A propensity scoring methodology was used to minimize confounding. Treatment with remdesivir, dexamethasone or both was assessed against standard of care. The primary outcome was a neurological complication occurring at the point of death, discharge, or resolution of the COVID-19 clinical episode. RESULTS: Out of 89,297 hospital inpatients, 64,088 had severe COVID-19 and 25,209 had non-hypoxic COVID-19. Neurological complications developed in 4.8% and 4.5% respectively. In both groups, neurological complications associated with increased mortality, ICU admission, worse self-care on discharge and time to recovery. In severe COVID-19, treatment with dexamethasone (n=21,129), remdesivir (n=1,428) and both combined (n=10,846) associated with a lower frequency of neurological complications: OR=0.76 (95% CI=0.69-0.83), OR 0.69 (95% CI=0.51-0.90) and OR=0.54, (95% CI=0.47-0.61) respectively. In non-hypoxic COVID-19, dexamethasone (n=2,580) associated with less neurological complications (OR=0.78, 95% CI 0.62-0.97), while the dexamethasone/remdesivir combination (n=460) showed a similar trend (OR=0.63, 95% CI=0.31-1.15). INTERPRETATION: Treatment with dexamethasone, remdesivir or both in patients hospitalised with COVID-19 associated with a lower frequency of neurological complications in an additive manner, such that the greatest benefit was observed in patients who received both drugs together. This article is protected by copyright. All rights reserved

Evidence for Efimov quantum states in an ultracold gas of cesium atoms

Systems of three interacting particles are notorious for their complex physical behavior. A landmark theoretical result in few-body quantum physics is Efimov's prediction of a universal set of bound trimer states appearing for three identical bosons with a resonant two-body interaction. Counterintuitively, these states even exist in the absence of a corresponding two-body bound state. Since the formulation of Efimov's problem in the context of nuclear physics 35 years ago, it has attracted great interest in many areas of physics. However, the observation of Efimov quantum states has remained an elusive goal. Here we report the observation of an Efimov resonance in an ultracold gas of cesium atoms. The resonance occurs in the range of large negative two-body scattering lengths, arising from the coupling of three free atoms to an Efimov trimer. Experimentally, we observe its signature as a giant three-body recombination loss when the strength of the two-body interaction is varied. We also detect a minimum in the recombination loss for positive scattering lengths, indicating destructive interference of decay pathways. Our results confirm central theoretical predictions of Efimov physics and represent a starting point with which to explore the universal properties of resonantly interacting few-body systems. While Feshbach resonances have provided the key to control quantum-mechanical interactions on the two-body level, Efimov resonances connect ultracold matter to the world of few-body quantum phenomena.Comment: 18 pages, 3 figure

Extracellular electrical signals in a neuron-surface junction: model of heterogeneous membrane conductivity

Signals recorded from neurons with extracellular planar sensors have a wide range of waveforms and amplitudes. This variety is a result of different physical conditions affecting the ion currents through a cellular membrane. The transmembrane currents are often considered by macroscopic membrane models as essentially a homogeneous process. However, this assumption is doubtful, since ions move through ion channels, which are scattered within the membrane. Accounting for this fact, the present work proposes a theoretical model of heterogeneous membrane conductivity. The model is based on the hypothesis that both potential and charge are distributed inhomogeneously on the membrane surface, concentrated near channel pores, as the direct consequence of the inhomogeneous transmembrane current. A system of continuity equations having non-stationary and quasi-stationary forms expresses this fact mathematically. The present work performs mathematical analysis of the proposed equations, following by the synthesis of the equivalent electric element of a heterogeneous membrane current. This element is further used to construct a model of the cell-surface electric junction in a form of the equivalent electrical circuit. After that a study of how the heterogeneous membrane conductivity affects parameters of the extracellular electrical signal is performed. As the result it was found that variation of the passive characteristics of the cell-surface junction, conductivity of the cleft and the cleft height, could lead to different shapes of the extracellular signals

Pathotypic diversity of Hyaloperonospora brassicae collected from Brassica oleracea

Downy mildew caused by Hyaloperonospora brassicae is an economically destructive disease of brassica crops in many growing regions throughout the world. Specialised pathogenicity of downy mildews from different Brassica species and closely related ornamental or wild relatives has been described from host range studies. Pathotypic variation amongst Hyaloperonospora brassicae isolates from Brassica oleracea has also been described; however, a standard set of B. oleracea lines that could enable reproducible classification of H. brassicae pathotypes was poorly developed. For this purpose, we examined the use of eight genetically refined host lines derived from our previous collaborative work on downy mildew resistance as a differential set to characterise pathotypes in the European population of H. brassicae. Interaction phenotypes for each combination of isolate and host line were assessed following drop inoculation of cotyledons and a spectrum of seven phenotypes was observed based on the level of sporulation on cotyledons and visible host responses. Two host lines were resistant or moderately resistant to the entire collection of isolates, and another was universally susceptible. Five lines showed differential responses to the H. brassicae isolates. A minimum of six pathotypes and five major effect resistance genes are proposed to explain all of the observed interaction phenotypes. The B. oleracea lines from this study can be useful for monitoring pathotype frequencies in H. brassicae populations in the same or other vegetable growing regions, and to assess the potential durability of disease control from different combinations of the predicted downy mildew resistance genes