First-principles study of (BiScO3){1-x}-(PbTiO3){x} piezoelectric alloys

We report a first-principles study of a class of (BiScO3)_{1-x}-(PbTiO3)_x (BS-PT) alloys recently proposed by Eitel et al. as promising materials for piezoelectric actuator applications. We show that (i) BS-PT displays very large structural distortions and polarizations at the morphotropic phase boundary (MPB) (we obtain a c/a of ~1.05-1.08 and P_tet of ~1.1 C/m^2); (ii) the ferroelectric and piezoelectric properties of BS-PT are dominated by the onset of hybridization between Bi/Pb-6p and O-2p orbitals, a mechanism that is enhanced upon substitution of Pb by Bi; and (iii) the piezoelectric responses of BS-PT and Pb(Zr_{1-x}Ti_x)O3 (PZT) at the MPB are comparable, at least as far as the computed values of the piezoelectric coefficient d_15 are concerned. While our results are generally consistent with experiment, they also suggest that certain intrinsic properties of BS-PT may be even better than has been indicated by experiments to date. We also discuss results for PZT that demonstrate the prominent role played by Pb displacements in its piezoelectric properties.Comment: 6 pages, with 3 postscript figures embedded. Uses REVTEX and epsf macros. Also available at http://www.physics.rutgers.edu/~dhv/preprints/ji_bi/index.htm

Dipolar cortico-muscular electrical stimulation: a novel method that enhances motor function in both - normal and spinal cord injured mice

<p>Abstract</p> <p>Background</p> <p>Electrical stimulation of the central and peripheral nervous systems is a common tool that is used to improve functional recovery after neuronal injury.</p> <p>Methods</p> <p>Here we described a new configuration of electrical stimulation as it was tested in anesthetized control and spinal cord injury (SCI) mice. Constant voltage output was delivered through two electrodes. While the negative voltage output (ranging from -1.8 to -2.6 V) was delivered to the muscle via transverse wire electrodes (diameter, 500 μm) located at opposite ends of the muscle, the positive output (ranging from + 2.4 to +3.2 V) was delivered to the primary motor cortex (M1) (electrode tip, 100 μm). The configuration was named dipolar cortico-muscular stimulation (dCMS) and consisted of 100 pulses (1 ms pulse duration, 1 Hz frequency).</p> <p>Results</p> <p>In SCI animals, after dCMS, cortically-elicited muscle contraction improved markedly at the contralateral (456%) and ipsilateral (457%) gastrocnemius muscles. The improvement persisted for the duration of the experiment (60 min). The enhancement of cortically-elicited muscle contraction was accompanied by the reduction of M1 maximal threshold and the potentiation of spinal motoneuronal evoked responses at the contralateral (313%) and ipsilateral (292%) sides of the spinal cord. Moreover, spontaneous activity recorded from single spinal motoneurons was substantially increased contralaterally (121%) and ipsilaterally (54%). Interestingly, spinal motoneuronal responses and muscle twitches evoked by the test stimulation of non-treated M1 (received no dCMS) were significantly enhanced as well. Similar results obtained from normal animals albeit the changes were relatively smaller.</p> <p>Conclusion</p> <p>These findings demonstrated that dCMS could improve functionality of corticomotoneuronal pathway and thus it may have therapeutic potential.</p

Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis

The incidence of brain metastasis is increasing, however, little is known about molecular mechanism responsible for lung cancer-derived brain metastasis and their development in the brain. In the present study, brain pathology was examined in an experimental model system of brain metastasis as well as in human brain with lung cancer metastasis. In an experimental model, after 3–6 weeks of intracardiac inoculation of human lung cancer-derived (HARA-B) cells in nude mice, wide range of brain metastases were observed. The brain sections showed significant increase in glial fibrillary acidic protein (GFAP)-positive astrocytes around metastatic lesions. To elucidate the role of astrocytes in lung cancer proliferation, the interaction between primary cultured mouse astrocytes and HARA-B cells was analyzed in vitro. Co-cultures and insert-cultures demonstrated that astrocytes were activated by tumor cell-oriented factors; macrophage migration inhibitory factor (MIF), interleukin-8 (IL-8) and plasminogen activator inhibitor-1 (PAI-1). Activated astrocytes produced interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β), which in turn promoted tumor cell proliferation. Semi-quantitative immunocytochemistry showed that increased expression of receptors for IL-6 and its subunits gp130 on HARA-B cells. Receptors for TNF-α and IL-1β were also detected on HARA-B cells but down-regulated after co-culture with astrocytes. Insert-culture with astrocytes also stimulated the proliferation of other lung cancer-derived cell lines (PC-9, QG56, and EBC-1). These results suggest that tumor cells and astrocytes stimulate each other and these mutual relationships may be important to understand how lung cancer cells metastasize and develop in the brain

Tunable Growth Factor Delivery from Injectable Hydrogels for Tissue Engineering

Current sustained delivery strategies of protein therapeutics are limited by the fragility of the protein, resulting in minimal quantities of bioactive protein delivered. In order to achieve prolonged release of bioactive protein, an affinity-based approach was designed which exploits the specific binding of the Src homology 3 (SH3) domain with short proline-rich peptides. Specifically, methyl cellulose was modified with SH3-binding peptides (MC-peptide) with either a weak affinity or strong affinity for SH3. The release profile of SH3-rhFGF2 fusion protein from hyaluronan MC-SH3 peptide (HAMC-peptide) hydrogels was investigated and compared to unmodified controls. SH3-rhFGF2 release from HAMC-peptide was extended to 10 days using peptides with different binding affinities compared to the 48 h release from unmodified HAMC. This system is capable of delivering additional proteins with tunable rates of release, while maintaining bioactivity, and thus is broadly applicable

P2X receptor-mediated purinergic sensory pathways to the spinal cord dorsal horn

P2X receptors are expressed on different functional groups of primary afferent fibers. P2X receptor-mediated sensory inputs can be either innocuous or nociceptive, depending on which dorsal horn regions receive these inputs. We provide a brief review of P2X receptor-mediated purinergic sensory pathways to different regions in the dorsal horn. These P2X purinergic pathways are identified in normal animals, which provides insights into their physiological functions. Future studies on P2X purinergic pathways in animal models of pathological conditions may provide insights on how P2X receptors play a role in pathological pain states

Biomarkers for Severity of Spinal Cord Injury in the Cerebrospinal Fluid of Rats

One of the major challenges in management of spinal cord injury (SCI) is that the assessment of injury severity is often imprecise. Identification of reliable, easily quantifiable biomarkers that delineate the severity of the initial injury and that have prognostic value for the degree of functional recovery would significantly aid the clinician in the choice of potential treatments. To find such biomarkers we performed quantitative liquid chromatography-mass spectrometry (LC-MS/MS) analyses of cerebrospinal fluid (CSF) collected from rats 24 h after either a moderate or severe SCI. We identified a panel of 42 putative biomarkers of SCI, 10 of which represent potential biomarkers of SCI severity. Three of the candidate biomarkers, Ywhaz, Itih4, and Gpx3 were also validated by Western blot in a biological replicate of the injury. The putative biomarkers identified in this study may potentially be a valuable tool in the assessment of the extent of spinal cord damage

Distinct Peripheral Blood RNA Responses to Salmonella in Pigs Differing in Salmonella Shedding Levels: Intersection of IFNG, TLR and miRNA Pathways

Transcriptomic analysis of the response to bacterial pathogens has been reported for several species, yet few studies have investigated the transcriptional differences in whole blood in subjects that differ in their disease response phenotypes. Salmonella species infect many vertebrate species, and pigs colonized with Salmonella enterica serovar Typhimurium (ST) are usually asymptomatic, making detection of these Salmonella-carrier pigs difficult. The variable fecal shedding of Salmonella is an important cause of foodborne illness and zoonotic disease. To investigate gene pathways and biomarkers associated with the variance in Salmonella shedding following experimental inoculation, we initiated the first analysis of the whole blood transcriptional response induced by Salmonella. A population of pigs (n = 40) was inoculated with ST and peripheral blood and fecal Salmonella counts were collected between 2 and 20 days post-inoculation (dpi). Two groups of pigs with either low shedding (LS) or persistent shedding (PS) phenotypes were identified. Global transcriptional changes in response to ST inoculation were identified by Affymetrix Genechip® analysis of peripheral blood RNA at day 0 and 2 dpi. ST inoculation triggered substantial gene expression changes in the pigs and there was differential expression of many genes between LS and PS pigs. Analysis of the differential profiles of gene expression within and between PS and LS phenotypic classes identified distinct regulatory pathways mediated by IFN-γ, TNF, NF-κB, or one of several miRNAs. We confirmed the activation of two regulatory factors, SPI1 and CEBPB, and demonstrated that expression of miR-155 was decreased specifically in the PS animals. These data provide insight into specific pathways associated with extremes in Salmonella fecal shedding that can be targeted for further exploration on why some animals develop a carrier state. This knowledge can also be used to develop rational manipulations of genetics, pharmaceuticals, nutrition or husbandry methods to decrease Salmonella colonization, shedding and spread

P2 receptors and chronic pain

There is abundant evidence that extracellular ATP and other nucleotides have an important role in pain signaling at both the periphery and in the CNS. The focus of attention now is on the possibility that endogenous ATP and its receptor system might be activated in chronic pathological pain states, particularly in neuropathic and inflammatory pain. Neuropathic pain is often a consequence of nerve injury through surgery, bone compression, diabetes or infection. This type of pain can be so severe that even light touching can be intensely painful; unfortunately, this state is generally resistant to currently available treatments. In this review, we summarize the role of ATP receptors, particularly the P2X4, P2X3 and P2X7 receptors, in neuropathic and inflammatory pain. The expression of P2X4 receptors in the spinal cord is enhanced in spinal microglia after peripheral nerve injury, and blocking pharmacologically and suppressing molecularly P2X4 receptors produce a reduction of the neuropathic pain behaviour. Understanding the key roles of these ATP receptors may lead to new strategies for the management of intractable chronic pain

An overview of tissue engineering approaches for management of spinal cord injuries

Severe spinal cord injury (SCI) leads to devastating neurological deficits and disabilities, which necessitates spending a great deal of health budget for psychological and healthcare problems of these patients and their relatives. This justifies the cost of research into the new modalities for treatment of spinal cord injuries, even in developing countries. Apart from surgical management and nerve grafting, several other approaches have been adopted for management of this condition including pharmacologic and gene therapy, cell therapy, and use of different cell-free or cell-seeded bioscaffolds. In current paper, the recent developments for therapeutic delivery of stem and non-stem cells to the site of injury, and application of cell-free and cell-seeded natural and synthetic scaffolds have been reviewed