Contribution of cytoskeletal elements to the axonal mechanical properties

Background

Microtubules, microfilaments, and neurofilaments are cytoskeletal elements that affect cell morphology, cellular processes, and mechanical structures in neural cells. The objective of the current study was to investigate the contribution of each type of cytoskeletal element to the mechanical properties of axons of dorsal root and sympathetic ganglia cells in chick embryos.

Results

Microtubules, microfilaments, and neurofilaments in axons were disrupted by nocodazole, cytochalasin D, and acrylamide, respectively, or a combination of the three. An atomic force microscope (AFM) was then used to compress the treated axons, and the resulting corresponding force-deformation information was analyzed to estimate the mechanical properties of axons that were partially or fully disrupted.

Conclusion

We have found that the mechanical stiffness was most reduced in microtubules-disrupted-axons, followed by neurofilaments-disrupted- and microfilaments-disrupted-axons. This suggests that microtubules contribute the most of the mechanical stiffness to axons.

     

Artery buckling affects the mechanical stress in atherosclerotic plaques

Background

Tortuous arteries are often seen in patients with hypertension and atherosclerosis. While the mechanical stress in atherosclerotic plaque under lumen pressure has been studied extensively, the mechanical stability of atherosclerotic arteries and subsequent effect on the plaque stress remain unknown. To this end, we investigated the buckling and post-buckling behavior of model stenotic coronary arteries with symmetric and asymmetric plaque.

Methods

Buckling analysis for a model coronary artery with symmetric and asymmetric plaque was conducted using finite element analysis based on the dimensions and nonlinear anisotropic materials properties reported in the literature.

Results

Artery with asymmetric plaque had lower critical buckling pressure compared to the artery with symmetric plaque and control artery. Buckling increased the peak stress in the plaque and led to the development of a high stress concentration in artery with asymmetric plaque. Stiffer calcified tissue and severe stenosis increased the critical buckling pressure of the artery with asymmetric plaque.

Conclusions

Arteries with atherosclerotic plaques are prone to mechanical buckling which leads to a high stress concentration in the plaques that can possibly make the plaques prone to rupture.

     

Heat shock protein 27 plays a protective role in thoracic aortic dissection by promoting cell proliferation and inhibiting apoptosis

Background

Thoracic aortic dissection (TAD) is one of the most severe aortic diseases. The study aimed to explore the potential role of heat shock protein 27 (HSP27) in the pathogenesis of TAD using an in vitro model of oxidative stress in vascular smooth muscle cells (VSMCs).

Methods

HSP27 was analyzed in aortic surgical specimens from 12 patients with TAD and 8 healthy controls. A lentiviral vector was used to overexpress HSP27 in rat aortic VSMCs. Cell proliferation and apoptosis were measured under oxidative stress induced by H₂O₂.

Results

HSP27 expression was significantly higher in aortic tissue from patients with TAD and VSMCs in the aortic media were the main cell type producing HSP27. Elevated oxidative stress was also detected in the TAD samples. Overexpression of HSP27 significantly attenuated H₂O₂-induced inhibition of cell proliferation. Furthermore, HSP27 was found to decrease H₂O₂-induced cell apoptosis and oxidative stress.

Conclusions

These results suggest that HSP27 expression promotes VSMC viability, suppresses cell apoptosis, and confers protection against oxidative stress in TAD.

     

Minimal variation of the plasma lipidome after delayed processing of neonatal cord blood

Background

Cord blood lipids are potential disease biomarkers. We aimed to determine if their concentrations were affected by delayed blood processing.

Method

Refrigerated cord blood from six healthy newborns was centrifuged every 12 h for 4 days. Plasma lipids were analysed by liquid chromatography/mass spectroscopy.

Results

Of 262 lipids identified, only eight varied significantly over time. These comprised three dihexosylceramides, two phosphatidylserines and two phosphatidylethanolamines whose relative concentrations increased and one sphingomyelin that decreased.

Conclusion

Delay in separation of plasma from refrigerated cord blood has minimal effect overall on the plasma lipidome.

     

A library of mammalian effector modules for synthetic morphology

Background

In mammalian development, the formation of most tissues is achieved by a relatively small repertoire of basic morphogenetic events (e.g. cell adhesion, locomotion, apoptosis, etc.), permutated in various sequences to form different tissues. Together with cell differentiation, these mechanisms allow populations of cells to organize themselves into defined geometries and structures, as simple embryos develop into complex organisms. The control of tissue morphogenesis by populations of engineered cells is a potentially very powerful but neglected aspect of synthetic biology.

Results

We have assembled a modular library of synthetic morphogenetic driver genes to control (separately) mammalian cell adhesion, locomotion, fusion, proliferation and elective cell death. Here we describe this library and demonstrate its use in the T-REx-293 human cell line to induce each of these desired morphological behaviours on command.

Conclusions

Building on from the simple test systems described here, we want to extend engineered control of morphogenetic cell behaviour to more complex 3D structures that can inform embryologists and may, in the future, be used in surgery and regenerative medicine, making synthetic morphology a powerful tool for developmental biology and tissue engineering.

     

rDolphin: a GUI R package for proficient automatic profiling of 1D <Superscript>1</Superscript>H-NMR spectra of study datasets

Introduction

Adoption of automatic profiling tools for ¹H-NMR-based metabolomic studies still lags behind other approaches in the absence of the flexibility and interactivity necessary to adapt to the properties of study data sets of complex matrices.

Objectives

To provide an open source tool that fully integrates these needs and enables the reproducibility of the profiling process.

Methods

rDolphin incorporates novel techniques to optimize exploratory analysis, metabolite identification, and validation of profiling output quality.

Results

The information and quality achieved in two public datasets of complex matrices are maximized.

Conclusion

rDolphin is an open-source R package (http://github.com/danielcanueto/rDolphin) able to provide the best balance between accuracy, reproducibility and ease of use.

     

Influence of shifts over an 80-year period in forest composition on soil properties

Background and aims

Forest composition in North America has undergone important changes since the European settlement. The effects of such alterations on soil properties remain largely unknown. This study aims to understand the long-term effects of shifts in forest composition on soil properties.

Methods

Using data from 130 plots measured over an eighty-year period, the relationships between stand composition (both current and past), parent material and current soil chemical properties were studied with redundancy analyses.

Results

Results indicated that the parent material remained the dominant factor explaining soil properties, followed by current tree species composition. No legacy effect of past forest composition was found, but shifts in forest composition explained part of the current soil properties. Specifically, an increase in balsam fir was related to higher C/N ratio in the O-horizon, while an increase in maple species was related to higher net nitrification in both the O and B-horizons, and higher extractable P in the B-horizon.

Conclusion

Our results suggest that increasing the maple component at the expense of conifers over several decades may enhance nutrient availability in the O-horizon.

     

Statistical analysis of fractionation resistance by functional category and expression

Background

The current literature establishes the importance of gene functional category and expression in promoting or suppressing duplicate gene loss after whole genome doubling in plants, a process known as fractionation. Inspired by studies that have reported gene expression to be the dominating factor in preventing duplicate gene loss, we analyzed the relative effect of functional category and expression.

Methods

We use multivariate methods to study data sets on gene retention, function and expression in rosids and asterids to estimate effects and assess their interaction.

Results

Our results suggest that the effect on duplicate gene retention fractionation by functional category and expression are independent and have no statistical interaction.

Conclusion

In plants, functional category is the more dominant factor in explaining duplicate gene loss.

     

Speckle tracking echocardiography analyses of myocardial contraction efficiency predict response for cardiac resynchronization therapy

Background

In patients with left ventricular (LV) dysssynchrony, contraction that doesn’t fall into ejection period (LVEj) results in a waste of energy due to inappropriate contraction timing, which was now widely treated by cardiac resynchronization therapy(CRT). Myocardial Contraction Efficiency was defined as the ratio of Efficient Contraction Time (ECTR) and amplitude of efficient contraction (ECR) during LVEj against that in the entire cardiac cycle. This study prospectively investigated whether efficiency indexes could predict CRT outcome.

Methods

Our prospective pilot study including 70 CRT candidates, parameters of myocardial contraction timing and contractility were measured by speckle tracking echocardiography (STE) and efficiency indexes were calculated accordingly at baseline and at 6-month follow-up. Primary outcome events were predefined as death or HF hospitalization, and secondary outcome events were defined as all-cause death during the follow-up. 16-segement Standard deviation of time to onset strain (TTO-16SD) and time to peak strain (TTP-16SD) were included as the dyssynchrony indexes.

Results

According to LV end systolic volume (LVESV) and LV eject fraction(LVEF) values at 6-month follow-up, subjects were classified into responder and non-responder groups, ECR (OR 0.87, 95%CI 0.78–0.97, P?<?0.05) and maximum longitudinal strain (MLS) (OR 2.22, 95%CI 1.36–3.61, P?<?0.01) were the two independent predictors for CRT response, Both TTO-16SD and TTP-16SD failed to predict outcome. Patients with poorer myocardial contraction efficiency and better contractility are more likely to benefit from CRT.

Conclusions

STE can evaluate left ventricular contraction efficiency and contractility to predict CRT response. When analyzing myocardial strain by STE, contraction during LVEj should be highlighted.

     

Prediction of heme binding residues from protein sequences with integrative sequence profiles

Background

The heme-protein interactions are essential for various biological processes such as electron transfer, catalysis, signal transduction and the control of gene expression. The knowledge of heme binding residues can provide crucial clues to understand these activities and aid in functional annotation, however, insufficient work has been done on the research of heme binding residues from protein sequence information.

Methods

We propose a sequence-based approach for accurate prediction of heme binding residues by a novel integrative sequence profile coupling position specific scoring matrices with heme specific physicochemical properties. In order to select the informative physicochemical properties, we design an intuitive feature selection scheme by combining a greedy strategy with correlation analysis.

Results

Our integrative sequence profile approach for prediction of heme binding residues outperforms the conventional methods using amino acid and evolutionary information on the 5-fold cross validation and the independent tests.

Conclusions

The novel feature of an integrative sequence profile achieves good performance using a reduced set of feature vector elements.

     

A new model for root growth in soil with macropores

Background and aims

The use of standard dynamic root architecture models to simulate root growth in soil containing macropores failed to reproduce experimentally observed root growth patterns. We thus developed a new, more mechanistic model approach for the simulation of root growth in structured soil.

Methods

In our alternative modelling approach, we distinguish between, firstly, the driving force for root growth, which is determined by the orientation of the previous root segment and the influence of gravitropism and, secondly, soil mechanical resistance to root growth. The latter is expressed by its inverse, soil mechanical conductance, and treated similarly to hydraulic conductivity in Darcy’s law. At the presence of macropores, soil mechanical conductance is anisotropic, which leads to a difference between the direction of the driving force and the direction of the root tip movement.

Results

The model was tested using data from the literature, at pot scale, at macropore scale, and in a series of simulations where sensitivity to gravity and macropore orientation was evaluated.

Conclusions

Qualitative and quantitative comparisons between simulated and experimentally observed root systems showed good agreement, suggesting that the drawn analogy between soil water flow and root growth is a useful one.

     

Retinal metabolic events in preconditioning light stress as revealed by wide-spectrum targeted metabolomics

Introduction

Light is the primary stimulus for vision, but may also cause damage to the retina. Pre-exposing the retina to sub-lethal amount of light (or preconditioning) improves chances for retinal cells to survive acute damaging light stress.

Objectives

This study aims at exploring the changes in retinal metabolome after mild light stress and identifying mechanisms that may be involved in preconditioning.

Methods

Retinas from 12 rats exposed to mild light stress (1000 lux?×?for 12 h) and 12 controls were collected one and seven days after light stress (LS). One retina was used for targeted metabolomics analysis using the Biocrates p180 kit while the fellow retina was used for histological and immunohistochemistry analysis.

Results

Immunohistochemistry confirmed that in this experiment, a mild LS with retinal immune response and minimal photoreceptor loss occurred. Compared to controls, LS induced an increased concentration in phosphatidylcholines. The concentration in some amino acids and biogenic amines, particularly those related to the nitric oxide pathway (like asymmetric dimethylarginine (ADMA), arginine and citrulline) also increased 1 day after LS. 7 days after LS, the concentration in two sphingomyelins and phenylethylamine was found to be higher. We further found that in controls, retina metabolome was different between males and females: male retinas had an increased concentration in tyrosine, acetyl-ornithine, phosphatidylcholines and (acyl)-carnitines.

Conclusions

Besides retinal sexual metabolic dimorphism, this study shows that preconditioning is mostly associated with re-organisation of lipid metabolism and changes in amino acid composition, likely reflecting the involvement of arginine-dependent NO signalling.

     

KniMet: a pipeline for the processing of chromatography–mass spectrometry metabolomics data

Introduction

Data processing is one of the biggest problems in metabolomics, given the high number of samples analyzed and the need of multiple software packages for each step of the processing workflow.

Objectives

Merge in the same platform the steps required for metabolomics data processing.

Methods

KniMet is a workflow for the processing of mass spectrometry-metabolomics data based on the KNIME Analytics platform.

Results

The approach includes key steps to follow in metabolomics data processing: feature filtering, missing value imputation, normalization, batch correction and annotation.

Conclusion

KniMet provides the user with a local, modular and customizable workflow for the processing of both GC–MS and LC–MS open profiling data.

     

Metabolic interaction between purine nucleotide cycle and oxypurine cycle during skeletal muscle contraction of different intensities: a biochemical reappraisal

Background

A substrate cycle is a metabolic transformation in which a substrate A is phosphorylated to A?P at the expense of ATP (or another “high energy” compound), and A?P is converted back to A by a nucleotidase or a phosphatase. Many biochemists resisted the idea of such an ATP waste. Why a non-phosphorylated metabolite should be converted into a phosphorylated form, and converted back to its non-phosphorylated form through a “futile cycle”?

Aim of review

In this Review we aim at presenting our present knowledge on the biochemical features underlying the interrelation between the muscle purine nucleotide cycle and the oxypurine cycle, and on the metabolic responses of the two cycles to increasing intensities of muscle contraction.

Key scientific concepts of review

Nowadays it is widely accepted that the substrate cycles regulate many vital functions depending on the expense of large amounts of ATP, including skeletal muscle contraction, so that the expense of some extra ATP and “high energy” compounds, such as GTP and PRPP via substrate cycles, is not surprising. The Review emphasizes the strict metabolic interrelationship between the purine nucleotide cycle and the oxipurine cycle.

     

Collagen and fibronectin surface modification of nanoporous anodic alumina and macroporous silicon for endothelial cell cultures

Background

The ability to direct the cellular response by means of biomaterial surface topography is important for biomedical applications. Substrate surface topography has been shown to be an effective cue for the regulation of cellular response. Here, the response of human aortic endothelial cells to nanoporous anodic alumina and macroporous silicon with collagen and fibronectin functionalization has been studied.

Methods

Confocal microscopy and scanning electron microscopy were employed to analyse the effects of the material and the porosity on the adhesion, morphology, and proliferation of the cells. Cell spreading and filopodia formation on macro- and nanoporous material was characterized by atomic force microscopy. We have also studied the influence of the protein on the adhesion.

Results

It was obtained the best results when the material is functionalized with fibronectin, regarding cells adhesion, morphology, and proliferation.

Conclusion

These results permit to obtain chemical modified 3D structures for several biotechnology applications such as tissue engineering, organ-on-chip or regenerative medicine.

     

A methodology for elucidating regulatory mechanisms leading to changes in lipid profiles

Introduction

It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.

Objectives

This work simplifies this process.

Methods

A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.

Results

The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.

Conclusion

This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.

     

Metabolic risks at birth of neonates exposed in utero to HIV-antiretroviral therapy relative to unexposed neonates: an NMR metabolomics study of cord blood

Introduction

Antiretroviral therapy (ART) for HIV-infected pregnant women is highly effective in preventing mother-to-child transmission (PMTCT) of the virus, but deleterious metabolic and mitochondrial observations in infants born to HIV-infected women treated with ART during pregnancy are periodically reported.

Objectives

This study addresses the concern of HIV-ART-induced metabolic perturbations through a metabolomics study of cord blood collected during transitional neonatal hypoglycaemia following birth from newborns either exposed or unexposed to fetal HIV-ART.

Methods

Proton magnetic resonance spectra from cord blood of 11 in utero HIV-ART-exposed and 14 unexposed newborns, as well as serum from 8 control infants, generated 114 spectral bins which were used to identify significant metabolites by means of univariate and multivariate statistical analyses.

Results

The metabolite profiles differed significantly between that from the unexposed newborns and that from infants—interpreted to characterize the state of transitional neonatal hypoglycaemia (low glucose and high lactic acid and ketone bodies). Quantitative analysis of potential ATP generation showed no meaningful difference in the global metabolite profiles of HIV-ART-exposed and unexposed neonates, but Volcano plot analysis, affirmed by odds ratios, indicated that exposure to HIV-ART affected the plasma 3-hydroxybutyric acid and hypoxanthine concentrations.

Conclusions

The metabolite profile for transitional neonatal hypoglycaemia indicated that HIV-ART did not compromise the exposed neonates to the energy stress of allostasis experienced at birth. Increased hypoxanthine and 3-hydroxybutyric acid indicates metabolic stress at birth in some of the newborns exposed to HIV-ART and raises a concern about unrecognized prolonged allostasis with potential neurological consequences for these infants.