A gold dual‐microelectrode probe patterned on a silicon substrate for bio‐impedance measurement was fabricated, characterised and tested on different types of tissues. The aim of this study is to ...fabricate a device capable of using bioimpedance to discriminate different tissue types. This proof of concept of the device was characterised on meat and a gel/lard phantom which mimics fat and muscle. The initial results demonstrated that the gold dual‐microelectrode probe had excellent electrochemical recording potential. The bio‐impedance data derived was capable of differentiation between biological tissues. Bio‐impedance measurement may enhance cancer diagnostics by providing novel data in relation to cancer and surrounding healthy tissue. This manuscript describes the design, fabrication and validation of a gold dual‐microelectrode bioimpedance sensor with a potential future application in cancer diagnostics.
There is growing evidence that the imbalance between oxidative stress and the antioxidant defense system may
be associated with the development neuropsychiatric disorders, such as depression and ...anxiety. Major depression and
anxiety are presently correlated with a lowered total antioxidant state and by an activated oxidative stress (OS) pathway.
The classical antidepressants may produce therapeutic effects other than regulation of monoamines by increasing the
antioxidant levels and normalizing the damage caused by OS processes. This chapter provides an overview of recent work
on oxidative stress markers in the animal models of depression and anxiety, as well as patients with the aforementioned
mood disorders. It is well documented that antioxidants can remove the reactive oxygen species (ROS) and reactive
nitrogen species (RNS) through scavenging radicals and suppressing the OS pathway, which further protect against
neuronal damage caused oxidative or nitrosative stress sources in the brain, hopefully resulting in remission of depression
or anxiety symptoms. The functional understanding of the relationship between oxidative stress and depression and
anxiety may pave the way for discovery of novel targets for treatment of neuropsychiatric disorders.
Ultraviolet–visible (UV–vis), steady-state and time-resolved fluorescence, and Fourier transform-infrared (FT-IR) spectroscopy were used to study the interaction between maslinic acid (MA) and bovine ...serum albumin (BSA). Binding constants were determined at three different temperatures (298, 304, and 310K). Spectroscopic analysis revealed that the fluorescence-quenching mechanism between MA and BSA was a static quenching procedure. MA specifically binds to one site of the BSA molecule forming a stable complex with a binding constant of (5.4±0.4)×104M−1 at pH 7.4 and 298K. From the thermodynamic parameters of the binding process (ΔG0, ΔH0 and ΔS0) it can be inferred that hydrogen bonds and van der Waals interactions are the predominant intermolecular forces responsible for the stabilization of the complex. Anisotropy studies revealed that tryptophan residues of BSA undergo motion restrictions as a result of the interaction with MA. The distance between MA and the fluorophore residue of BSA was evaluated according to the theory of Föster for fluorescence resonance energy transfer (FRET). Observations from FT-IR spectra and three-dimensional fluorescence indicated changes in the conformation of BSA upon ligand binding.
•The interaction between MA and BSA was examined with spectroscopic techniques.•The interaction between MA and BSA was studied at different temperatures.•Fluorescence spectroscopy studies suggest that quenching mechanism is static.•The hydrogen bonds and van der Waals interactions are predominant forces.•Conformational changes of the protein upon binding of MA were observed.
The use of cell lines or animal models has significant disadvantages when dealing with a set of heterogeneous diseases such as epithelial ovarian cancer. This has clinical relevance in that ...biomarkers developed using cell line or animal models are often not transferable to the clinical setting. In this study, we describe the development of a robust protocol for developing primary cultures of ovarian cancer which will overcome some of these difficulties. Women undergoing surgery for ovarian cancer were recruited and samples of ascites and solid tumour deposits were used to develop primary cultures. Cells were characterised using a panel of immunofluorescent antibodies prior to use in a variety of assays including functional assessment of DNA repair pathways. During the four year study period, viable cultures, confirmed to be epithelial in origin were generated from 156 of 172 (91%) cases recruited. Characterisation was carried out using a panel of antibodies including pancytokeratin, CA125, EpCAM, MOC-31, D2-40 and vimentin. Senescence occurred between the 2nd and 8th passages in all cultures except one in which spontaneous immortalization occurred. Cells could be successfully cultured even after a period of storage at 4°C and cultured cells were capable of being used for a variety of applications including functional assays. Upon functional assessment there was minimal intra-tumour heterogeneity. It is therefore possible to derive viable ovarian cancer cell cultures in the majority of patients undergoing surgery. Cells cultured directly from patient cancers provide an accurate and highly diverse model.
Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each has a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic ...determination of the two diseases.
Genome-wide association data were obtained from the METASTROKE, Coronary Artery Disease Genome-wide Replication and Meta-analysis (CARDIoGRAM), and Coronary Artery Disease (C4D) Genetics consortia. We first analyzed common variants reaching a nominal threshold of significance (P<0.01) for CAD for their association with IS and vice versa. We then examined specific overlap across phenotypes for variants that reached a high threshold of significance. Finally, we conducted a joint meta-analysis on the combined phenotype of IS or CAD. Corresponding analyses were performed restricted to the 2167 individuals with the ischemic large artery stroke (LAS) subtype.
Common variants associated with CAD at P<0.01 were associated with a significant excess risk for IS and for LAS and vice versa. Among the 42 known genome-wide significant loci for CAD, 3 and 5 loci were significantly associated with IS and LAS, respectively. In the joint meta-analyses, 15 loci passed genome-wide significance (P<5×10(-8)) for the combined phenotype of IS or CAD and 17 loci passed genome-wide significance for LAS or CAD. Because these loci had prior evidence for genome-wide significance for CAD, we specifically analyzed the respective signals for IS and LAS and found evidence for association at chr12q24/SH2B3 (PIS=1.62×10(-7)) and ABO (PIS=2.6×10(-4)), as well as at HDAC9 (PLAS=2.32×10(-12)), 9p21 (PLAS=3.70×10(-6)), RAI1-PEMT-RASD1 (PLAS=2.69×10(-5)), EDNRA (PLAS=7.29×10(-4)), and CYP17A1-CNNM2-NT5C2 (PLAS=4.9×10(-4)).
Our results demonstrate substantial overlap in the genetic risk of IS and particularly the LAS subtype with CAD.
Aberrant expression of the proto‐oncogene BCL6 is a driver of tumorigenesis in diffuse large B cell lymphoma (DLBCL). Mice overexpressing BCL6 from the B cell‐specific immunoglobulin heavy chain μ ...intron promoter (Iμ‐Bcl6Tg/+) develop B cell lymphomas with features typical of human DLBCL. While the development of B cell lymphoma in these mice is tightly controlled by T cells, the mechanisms of this immune surveillance are poorly understood. Here we show that CD4 T cells contribute to the control of lymphoproliferative disease in lymphoma‐prone Iμ‐Bcl6Tg/+ mice. We reveal that this CD4 T cell immuno‐surveillance requires signaling by the co‐stimulatory molecule CD137 ligand (CD137L; also known as 4‐1BBL), which may promote the transition of pre‐malignant B cells with an activated phenotype into the germinal center stage via reverse signaling, preventing their hazardous accumulation. Thus, CD137L‐mediated CD4 T cell immuno‐surveillance adds another layer of protection against B cell malignancy to that provided by CD8 T cell cytotoxicity.
The mechanisms of immuno‐surveillance in BCL6‐driven B cell malignancy are poorly understood. In this study, we found that the CD137 ligand‐mediated signaling pathway and CD4 T cells acted as additional layers in immuno‐surveillance against BCL6‐driven B cell malignancy by limiting the expansion of activated, pre‐germinal center (GC) B cells.
Abstract
We investigated brain wiring in chronic schizophrenia and healthy controls in frontostriatal circuits using diffusion magnetic resonance imaging tractography in a novel way.
We extracted ...diffusion streamlines in 27 chronic schizophrenia and 26 healthy controls connecting 4 frontal subregions to the striatum. We labeled the projection zone striatal surface voxels into 2 subtypes: dominant-input from a single cortical subregion, and, functionally integrative, with mixed-input from diverse cortical subregions.
We showed: 1) a group difference for total striatal surface voxel number (P = .045) driven by fewer mixed-input voxels in the left (P = .007), but not right, hemisphere; 2) a group by hemisphere interaction for the ratio quotient between voxel subtypes (P = .04) with a left (P = .006), but not right, hemisphere increase in schizophrenia, also reflecting fewer mixed-input voxels; and 3) fewer mixed-input voxel counts in schizophrenia (P = .045) driven by differences in left hemisphere limbic (P = .007) and associative (P = .01), but not sensorimotor, striatum.
These results demonstrate a less integrative pattern of frontostriatal structural connectivity in chronic schizophrenia. A diminished integrative pattern yields a less complex input pattern to the striatum from the cortex with less circuit integration at the level of the striatum. Further, as brain wiring occurs during early development, aberrant brain wiring could serve as a developmental biomarker for schizophrenia.
Since the 2008/9 influenza season, the I-MOVE multicentre case-control study measures influenza vaccine effectiveness (VE) against medically-attended influenza-like-illness (ILI) laboratory confirmed ...as influenza. In 2011/12, European studies reported a decline in VE against influenza A(H3N2) within the season. Using combined I-MOVE data from 2010/11 to 2014/15 we studied the effects of time since vaccination on influenza type/subtype-specific VE. We modelled influenza type/subtype-specific VE by time since vaccination using a restricted cubic spline, controlling for potential confounders (age, sex, time of onset, chronic conditions). Over 10,000 ILI cases were included in each analysis of influenza A(H3N2), A(H1N1)pdm09 and B; with 4,759, 3,152 and 3,617 influenza positive cases respectively. VE against influenza A(H3N2) reached 50.6% (95% CI: 30.0-65.1) 38 days after vaccination, declined to 0% (95% CI: -18.1-15.2) from 111 days onwards. At day 54 VE against influenza A(H1N1)pdm09 reached 55.3% (95% CI: 37.9-67.9) and remained between this value and 50.3% (95% CI: 34.8-62.1) until season end. VE against influenza B declined from 70.7% (95% CI: 51.3-82.4) 44 days after vaccination to 21.4% (95% CI: -57.4-60.8) at season end. To assess if vaccination campaign strategies need revising more evidence on VE by time since vaccination is urgently needed.
The Ketogenic diet (KD) is an effective treatment with regards to treating pharmaco‐resistant epilepsy. However, there are difficulties around compliance and tolerability. Consequently, there is a ...need for refined/simpler formulations that could replicate the efficacy of the KD. One of the proposed hypotheses is that the KD increases cellular mitochondrial content which results in elevation of the seizure threshold. Here, we have focussed on the medium‐chain triglyceride form of the diet and the observation that plasma octanoic acid (C8) and decanoic acid (C10) levels are elevated in patients on the medium‐chain triglyceride KD. Using a neuronal cell line (SH‐SY5Y), we demonstrated that 250‐μM C10, but not C8, caused, over a 6‐day period, a marked increase in the mitochondrial enzyme, citrate synthase along with complex I activity and catalase activity. Increased mitochondrial number was also indicated by electron microscopy. C10 is a reported peroxisome proliferator activator receptor γ agonist, and the use of a peroxisome proliferator activator receptor γ antagonist was shown to prevent the C10‐mediated increase in mitochondrial content and catalase. C10 may mimic the mitochondrial proliferation associated with the KD and raises the possibility that formulations based on this fatty acid could replace a more complex diet.
We propose that decanoic acid (C10) results in increased mitochondrial number. Our data suggest that this may occur via the activation of the PPARγ receptor and its target genes involved in mitochondrial biogenesis. This finding could be of significant benefit to epilepsy patients who are currently on a strict ketogenic diet. Evidence that C10 on its own can modulate mitochondrial number raises the possibility that a simplified and less stringent C10‐based diet could be developed.
We propose that decanoic acid (C10) results in increased mitochondrial number. Our data suggest that this may occur via the activation of the PPARγ receptor and its target genes involved in mitochondrial biogenesis. This finding could be of significant benefit to epilepsy patients who are currently on a strict ketogenic diet. Evidence that C10 on its own can modulate mitochondrial number raises the possibility that a simplified and less stringent C10‐based diet could be developed.
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