Physical disruption of intervertebral disc promotes cell clustering and a degenerative phenotype

© 2019, The Author(s). To test the hypothesis that physical disruption of an intervertebral disc disturbs cell-matrix binding, leading to cell clustering and increased expression of matrix degrading enzymes that contribute towards degenerative disc cell phenotype. Lumbar disc tissue was removed at surgery from 21 patients with disc herniation, 11 with disc degeneration, and 8 with adolescent scoliosis. 5 μm sections were examined with histology, and 30-µm sections by confocal microscopy. Antibodies were used against integrin α5beta1, matrix metalloproteinases (MMP) 1, MMP-3, caspase 3, and denatured collagen types I and II. Spatial associations were sought between cell clustering and various degenerative features. An additional, 11 non-herniated human discs were used to examine causality: half of each specimen was cultured in a manner that allowed free ‘unconstrained’ swelling (similar to a herniated disc in vivo), while the other half was cultured within a perspex ring that allowed ‘constrained’ swelling. Changes were monitored over 36 h using live-cell imaging. 1,9-Di-methyl methylene blue (DMMB) assay for glycosaminoglycan loss was carried out from tissue medium. Partially constrained specimens showed little swelling or cell movement in vitro. In contrast, unconstrained swelling significantly increased matrix distortion, glycosaminoglycan loss, exposure of integrin binding sites, expression of MMPs 1 and 3, and collagen denaturation. In the association studies, herniated disc specimens showed changes that resembled unconstrained swelling in vitro. In addition, they exhibited increased cell clustering, apoptosis, MMP expression, and collagen denaturation compared to ‘control’ discs. Results support our hypothesis. Further confirmation will require longitudinal animal experiments

Modelling excited species and their role on kinetic pathways in the non-oxidative coupling of methane by dielectric barrier discharge

Acknowledgments We acknowledge and greatly appreciate the assistance from Dr. Mihailova from Plasma Matters B.V. in working with the software Plasimo and from Dr Marcus Campbell Bannerman from the University of Aberdeen for providing access to the computational cluster used for carrying out the simulations in this work. The work was supported by the UK Engineering and Physical Sciences Research Council (EPSRC) New Investigator Award, grant no. EP/R031800/1.Peer reviewedPostprin

S@M, a Mathematica Implementation of the SpinorFormalism

In this paper we present the package S@M (Spinors@Mathematica) which implements the spinor formalism in Mathematica. The package allows the use of complex-spinor algebra along with the multi-purpose features of Mathematica. The package defines the spinor objects with their basic properties along with functions to manipulate them. It also offers the possibility of evaluating the spinorial objects numerically at every computational step. The package is therefore well suited to be used the context of on-shell technology, in particular for the evaluation of scattering amplitudes at tree- and loop-level

Autofeedback scheme for preservation of macroscopic coherence in microwave cavities

We present a scheme for controlling the decoherence of a linear superposition of two coherent states with opposite phases in a high-Q microwave cavity, based on the injection of appropriately prepared ``probe'' and ``feedback'' Rydberg atoms, improving the one presented in [D. Vitali et al., Phys. Rev. Lett. 79, 2442 (1997)]. In the present scheme, the information transmission from the probe to the feedback atom is directly mediated by a second auxiliary cavity. The detection efficiency for the probe atom is no longer a critical parameter, and the decoherence time of the superposition state can be significantly increased using presently available technology.Comment: revtex, 15 pages, 4 eps figure

Sources of Stress, Family Functioning, and Needs of Families With a Chronic Critically Ill Child: A Qualitative Study.

PICU hospitalization is particularly stressful for families. When it is prolonged and the prognostic is uncertain, it can significantly and negatively affect the whole family. To date, little is known on how families with a chronic critically ill (CCI) child are affected. This national study explored the specific PICU-related sources of stress, family functioning and needs of families of CCI patients during a PICU hospitalization. This descriptive qualitative study was conducted in the eight pediatric intensive care units in Switzerland. Thirty-one families with a child meeting the CCI criteria participated in semi-structured interviews. Interviews, including mothers only (n = 12), fathers only (n = 8), or mother and father dyads (n = 11), were conducted in German, French, or English by two trained researchers/clinical nurses specialists. Interviews were recorded, transcribed verbatim, and analyzed using deductive and inductive content analyses. Five overarching themes emerged: (1) high emotional intensity, (2) PICU-related sources of stress, (3) evolving family needs, (4) multi-faceted family functioning, and (5) implemented coping strategies. Our study highlighted the importance of caring for families with CCI children. Parents reported high negative emotional responses that affect their family functioning. Families experience was highly dependent on how HCPs were able to meet the parental needs, provide emotional support, reinforce parental empowerment, and allow high quality of care coordination

Effect of Exercise Training on Interleukin-6, Tumour Necrosis Factor Alpha and Functional Capacity in Heart Failure

Background. We pooled data from four studies, to establish whether exercise training programs were able to modulate systemic cytokine levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). A second aim was to establish if differences in ExT regimens are related to degree of change in cytokines and peak VO2. Methods. Data from four centres relating to training protocol, exercise capacity, and cytokine measures (TNF-alpha and IL-6) were pooled for analysis. Results. Data for 106 CHF patients were collated (98 men, age 62 ± 10 yrs, wt 79 ± 14 Kg). Patients were moderately impaired (peak VO2 16.9 ± 4.4 mls/kg/min), with moderate LV systolic dysfunction (EF 30 ± 6.9%), 78% (83) had ischaemic cardiomyopathy. After ExT, peak VO2 increased 1.4 ± 3.4 ml/kg/min (P < .001), serum TNF-alpha decreased 1.9 ± 8.6 pg/ml (P = .02) and IL-6 was not significantly changed (0.5 ± 5.4 pg/ml, P = .32) for the whole group. Baseline and post-training peak VO2 changes were not correlated with change in cytokine levels. Conclusions. Exercise training reduces levels TNF-alpha but not IL-6 in CHF. However, across a heterogenic patient group, change in peak VO2 was not correlated with alterations in cytokine levels. While greater exercise volume (hours) was superior in improving peak VO2, no particular characteristic of ExT regimes appeared superior in effecting change in serum cytokines

Parametric Self-Oscillation via Resonantly Enhanced Multiwave Mixing

We demonstrate an efficient nonlinear process in which Stokes and anti-Stokes components are generated spontaneously in a Raman-like, near resonant media driven by low power counter-propagating fields. Oscillation of this kind does not require optical cavity and can be viewed as a spontaneous formation of atomic coherence grating

Ecohydrology: processes and implications for rangelands

This chapter is organized around the concept of ecohydrological processes that are explicitly tied to ecosystem services. Ecosystem services are benefits that people receive from ecosystems. We focus on (1) the regulating services of water distribution, water purification, and climate regulation; (2) the supporting services of water and nutrient cycling and soil protection and restoration; and (3) the provisioning services of water supply and biomass production. Regulating services are determined at the first critical juncture of the water cycle—on the soil surface, where water either infiltrates or becomes overland flow. Soil infiltrability is influenced by vegetation, grazing intensity, brush management, fire patterns, condition of biological soil crusts, and activity by fauna. At larger scales, water-regulating services are influenced by other factors, such as the nature and structure of riparian zones and the presence of shallow groundwater aquifers. Provisioning services are those goods or products that are directly produced from ecosystems, such as water, food, and fiber. Work over the last several decades has largely overturned the notion that water supply can be substantially increased by removal of shrubs. In riparian areas, surprisingly, removal of invasive, non-native woody plants appears to hold little potential for increasing water supply. Here, the primary factor appears to be that non-native plants use no more water than the native vegetation they displace. Clearly there is a close coupling between biota (both fauna and flora) and water on rangelands—which is why water-related ecosystem services are so strongly dependent on land management strategies.Fil: Wilcox, Bradford P.. Texas A&M University; Estados UnidosFil: Le Maitre, David. Council for Scientific and Industrial Research; SudáfricaFil: Jobbagy Gampel, Esteban Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi". Universidad Nacional de San Luis. Facultad de Ciencias Físico, Matemáticas y Naturales. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi"; ArgentinaFil: Wang, Lixin. Indiana University; Estados UnidosFil: Breshears, David D.. University of Arizona; Estados Unido

Recapitulating Parkinson's disease pathology in a three-dimensional human neural cell culture model.

Extensive loss of dopaminergic neurons, and aggregation of the protein α-synuclein into ubiquitin-positive Lewy bodies represents a major neuropathological hallmark of Parkinson's disease. At present the generation of large nuclear-associated Lewy bodies from endogenous wild-type α-synuclein, translationally regulated under its own promoter in human cell culture models requires costly and time-consuming protocols. Here, we demonstrate that fully differentiated human SH-SY5Y neuroblastoma cells grown in three-dimensional cell culture develop Lewy body-like pathology upon exposure to exogenous α-synuclein species. In contrast to most cell- and rodent-based models that exhibit multiple diffuse α-synuclein aggregates throughout the cytoplasm, a single large nuclear inclusion immuno-positive for α-synuclein and ubiquitin is rapidly obtained in our model. This was achieved, without the need for over-expression of α-synuclein or genetic modification of the cell line. However, phosphorylation of α-synuclein within these inclusions was not observed. The system described here provides an ideal tool to screen compounds to therapeutically intervene in Lewy body formation and to investigate the mechanisms involved in disease progression in synucleinopathies