Abnormal changes in voltage-gated sodium channels NaV1.1, NaV1.2, NaV1.3, NaV1.6 and in Calmodulin/calmodulin-dependent protein kinase II, within the brains of spontaneously epileptic rats and tremor rats

Voltage-gated sodium channels (VGSCs) play a crucial role in epilepsy. The expressions of different VGSCs subtypes are varied in diverse animal models of epilepsy that may reflect their multiple phenotypes or the complexity of the mechanisms of epilepsy. In a previous study, we reported that NaV1.1 and NaV1.3 were up-regulated in the hippocampus of the spontaneously epileptic rat (SER). In this study, we further analyzed both the expression and distribution of the typical VGSC subtypes NaV1.1, NaV1.2, NaV1.3 and NaV1.6 in the hippocampus and in the cortex of the temporal lobe of two genetic epileptic animal models: the SER and the tremor rat (TRM). The expressions of calmodulin (CaM) and calmodulin-dependent protein kinase II (CaMKII) were also analyzed with the purpose of assessing the effect of the CaM/CaMKII pathway in these two models of epilepsy. Increased expression of the four VGSC subtypes and CaM, accompanied by a decrease in CaMKII was observed in the hippocampus of both the SERs and the TRM rats. However, the changes observed in the expression of VGSC subtypes and CaM were decreased with an elevated CaMKII in the cortex of their temporal lobes. Double-labeled immunofluorescence data suggested that in SERs and TRM rats, the four subtypes of the VGSC proteins were present throughout the CA1, CA3 and dentate gyrus regions of the hippocampus and temporal lobe cortex and these were co-localized in neurons with CaM. These data represent the first evidence of abnormal changes in expression of four VGSC subtypes (NaV1.1, NaV1.2, NaV1.3 and NaV1.6) and CaM/CaMKII in the hippocampus and temporal lobe cortex of SERs and TRM rats. These changes may be involved in the generation of epileptiform activity and underlie the observed seizure phenotype in these rat models of genetic epilepsy.

Apolipoprotein-defined lipoproteins and apolipoproteins:Associations with abnormal albuminuria in type 1 diabetes in the diabetes control and complications trial/epidemiology of diabetes interventions and complications cohort

Dyslipoproteinemia has been associated with nephropathy in diabetes, with stronger correlations in men than in women. We aimed to characterize and compare plasma lipoprotein profiles associated with normal and increased albuminuria in men and women using apolipoprotein-defined lipoprotein subclasses and simple apolipoprotein measures.

Whole Slide Image Cytometry: a Novel Method for the Detection and Quantification of Abnormal DNA Contents in Barrett’s Oesophagus

Background: Barrett's oesophagus (BO) is a well recognized precursor of the majority of cases of oesophageal adenocarcinoma (OAC). Endoscopic surveillance of BO patients is frequently undertaken in an attempt to detect early OAC, high grade dysplasia (HGD) or low grade dysplasia (LGD). However histological interpretation and grading of dysplasia is subjective and poorly reproducible. The alternative flow cytometry and cytology-preparation image cytometry techniques require large amounts of tissue and specialist expertise which are not widely available for frontline health care.
Methods: This study has combined whole slide imaging with DNA image cytometry, to provide a novel method for the detection and quantification of abnormal DNA contents. 20 cases were evaluated, including 8 Barrett's specialised intestinal metaplasia (SIM), 6 LGD and 6 HGD. Feulgen stained oesophageal sections (1µm thickness) were digitally scanned in their entirety and evaluated to select regions of interests and abnormalities. Barrett’s mucosa was then interactively chosen for automatic nuclei segmentation where irrelevant cell types are ignored. The combined DNA content histogram for all selected image regions was then obtained. In addition, histogram measurements, including 5c exceeding ratio (xER-5C), 2c deviation index (2cDI) and DNA grade of malignancy (DNA-MG), were computed.
Results: The histogram measurements, xER-5C, 2cDI and DNA-MG, were shown to be effective in differentiating SIM from HGD, SIM from LGD, and LGD from HGD. All three measurements discriminated SIM from HGD cases successfully with statistical significance (pxER-5C=0.0041, p2cDI=0.0151 and pDNA-MG=0.0057). Statistical significance is also achieved differentiating SIM from LGD samples with pxER-5C=0.0019, p2cDI=0.0023 and pDNA-MG=0.0030. Furthermore the differences between LGD and HGD cases are statistical significant (pxER-5C=0.0289, p2cDI=0.0486 and pDNA-MG=0.0384).
Conclusion: Whole slide image cytometry is a novel and effective method for the detection and quantification of abnormal DNA content in BO. Compared to manual histological review, this proposed method is more objective and reproducible. Compared to flow cytometry and cytology-preparation image cytometry, the current method is low cost, simple to use and only requires a single 1µm tissue section. Whole slide image cytometry could assist the routine clinical diagnosis of dysplasia in BO, which is relevant for future progression risk to OAC.

The cross-section of stock returns in an early stock market

Using a new dataset which contains monthly data on 1015 stocks traded on the London Stock Exchange between 1825 and 1870, we investigate the cross section of stock returns in this early capital market. Unique features of this market allow us to evaluate the veracity of several popular explanations of asset pricing behavior. Using portfolio analysis and Fama–MacBeth regressions, we find that stock characteristics such as beta, illiquidity, dividend yield, and past-year return performance are all positively correlated with stock returns. However, market capitalization and past-three-year return performance have no significant correlation with stock returns.

Short-Term Reversals: The Effects of Past Returns and Institutional Exits

Price declines over the previous quarter lead to stronger reversals across the subsequent two months. We explain this finding based on the dual notions that liquidity provision can influence reversals, and agents that act as de facto liquidity providers may be less active in past losers. Supporting these observations, we find that active institutions participate less in losing stocks, and that the magnitude of monthly return reversals fluctuates with changes in the number of active institutional investors. Thus, we argue that fluctuations in liquidity provision with past return performance accounts for the link between return reversals and past returns.

Abnormal alterations in the Ca2+/CaV1.2/calmodulin/caMKII signaling pathway in a tremor rat model and in cultured hippocampal neurons exposed to Mg2+-free solution

Voltage-dependent calcium channels (VDCCs) are key elements in epileptogenesis. There are several binding-sites linked to calmodulin (CaM) and several potential CaM-dependent protein kinase II (CaMKII)-mediated phosphorylation sites in CaV1.2. The tremor rat model (TRM) exhibits absence‑like seizures from 8 weeks of age. The present study was performed to detect changes in the Ca2+/CaV1.2/CaM/CaMKII pathway in TRMs and in cultured hippocampal neurons exposed to Mg2+‑free solution. The expression levels of CaV1.2, CaM and phosphorylated CaMKII (p‑CaMKII; Thr‑286) in these two models were examined using immunofluorescence and western blotting. Compared with Wistar rats, the expression levels of CaV1.2 and CaM were increased, and the expression of p‑CaMKII was decreased in the TRM hippocampus. However, the expression of the targeted proteins was reversed in the TRM temporal cortex. A significant increase in the expression of CaM and decrease in the expression of CaV1.2 were observed in the TRM cerebellum. In the cultured neuron model, p‑CaMKII and CaV1.2 were markedly decreased. In addition, neurons exhibiting co‑localized expression of CaV1.2 and CaM immunoreactivities were detected. Furthermore, intracellular calcium concentrations were increased in these two models. For the first time, o the best of our knowledge, the data of the present study suggested that abnormal alterations in the Ca2+/CaV1.2/CaM/CaMKII pathway may be involved in epileptogenesis and in the phenotypes of TRMs and cultured hippocampal neurons exposed to Mg2+‑free solution.

Abnormal anti-Stokes Raman scattering of carbon nanotubes

Abnormal anti-Stokes Raman scattering (AASR) was unambiguously observed in carbon nanotubes (CNT's). In contrast to traditional Raman scattering theory, the absolute value of the Raman frequency of the anti-Stokes peak is not the same as that of the corresponding Stokes peak. It was demonstrated that AASR scattering originates from the unique nanoscale cylindrical structure of CNT's that can be considered naturally as a graphite structure with an intrinsic defect from its rolling. The double-resonance Raman scattering theory was applied to interpret the scattering mechanism of the AASR phenomenon successfully and quantitatively.

Abnormal Glycogen Storage by Retinal Neurons in Diabetes

PURPOSE: It is widely held that neurons of the central nervous system do not store glycogen and that accumulation of the polysaccharide may cause neurodegeneration. Since primary neural injury occurs in diabetic retinopathy, we examined neuronal glycogen status in the retina of streptozotocin-induced diabetic and control rats.

METHODS: Glycogen was localized in eyes of streptozotocin-induced diabetic and control rats using light microscopic histochemistry and electron microscopy, and correlated with immunohistochemical staining for glycogen phosphorylase and phosphorylated glycogen synthase (pGS).

RESULTS: Electron microscopy of 2-month-old diabetic rats (n = 6) showed massive accumulations of glycogen in the perinuclear cytoplasm of many amacrine neurons. In 4-month-old diabetic rats (n = 11), quantification of glycogen-engorged amacrine cells showed a mean of 26 cells/mm of central retina (SD ± 5), compared to 0.5 (SD ± 0.2) in controls (n = 8). Immunohistochemical staining for glycogen phosphorylase revealed strong expression in amacrine and ganglion cells of control retina, and increased staining in cell processes of the inner plexiform layer in diabetic retina. In control retina, the inactive pGS was consistently sequestered within the cell nuclei of all retinal neurons and the retinal pigment epithelium (RPE), but in diabetics nuclear pGS was reduced or lost in all classes of retinal cell except the ganglion cells and cone photoreceptors.

CONCLUSIONS: The present study identifies a large population of retinal neurons that normally utilize glycogen metabolism but show pathologic storage of the polysaccharide during uncontrolled diabetes.

Abnormal Pedestrian Trajectory analysis based on arbitrary-length clustering

This papers examines the use of trajectory distance measures and clustering techniques to define normal
and abnormal trajectories in the context of pedestrian tracking in public spaces. In order to detect abnormal
trajectories, what is meant by a normal trajectory in a given scene is firstly defined. Then every trajectory
that deviates from this normality is classified as abnormal. By combining Dynamic Time Warping and a
modified K-Means algorithms for arbitrary-length data series, we have developed an algorithm for trajectory
clustering and abnormality detection. The final system performs with an overall accuracy of 83% and 75%
when tested in two different standard datasets.