Time and frequency domain methods for quantifying common modulation of motor unit firing patterns

Background  

In investigations of the human motor system, two approaches are generally employed toward the identification of common modulating drives from motor unit recordings. One is a frequency domain method and uses the coherence function to determine the degree of linear correlation between each frequency component of the signals. The other is a time domain method that has been developed to determine the strength of low frequency common modulations between motor unit spike trains, often referred to in the literature as 'common drive'.     

Organoids as a Model for Colorectal Cancer

Modelling human diseases in in vitro systems is undisputedly an invaluable research tool, yet there are many limitations. Some of those limitations have been overcome through the introduction of organoid culture systems, which have revolutionised colorectal cancer research and enabled an array of new experimental techniques. This 3D system models the physiology, shape, dynamics and cell make-up of the intestinal epithelium producing a relevant and highly adaptable model system. The increased functional relevance of this model compared to the use of 2D cancer cell lines makes it an invaluable tool for both basic and translational research. As the limitations of this system are being overcome to make high-throughput assays possible, it is clear that organoids are becoming a mainstay of colorectal cancer research. This review aims to explore the advantages and limitations of this system and discusses the future directions enabled by this model.     

ELECTRON MICROSCOPIC STUDIES OF EXPERIMENTAL NEPHRITIS WITH FERRITIN-CONJUGATED ANTIBODY : LOCALIZATION OF ANTIGEN-ANTIBODY COMPLEXES IN RABBIT GLOMERULI FOLLOWING REPEATED INJECTIONS OF BOVINE SERUM ALBUMIN

Acute, subacute, and chronic glomerulonephritis, similar in certain features to human glomerulonephritis, has been produced in rabbits by repeated injections of bovine serum albumin. The ratio of antigen to antibody was the factor determining the development and type of glomerulonephritis. This is in confirmation of the observations of Dixon, Feldman, and Vazquez. With the aid of the ferritin antibody technique it was shown that antigen aggregates (probably antigen-antibody complexes) are present in the blood, cross the endothelium and the basement membrane, and accumulate as dense deposits between the basement membrane and the epithelial cytoplasm. In the deposits electron-dense aggregates formed by antigen or by antigen-antibody complexes and material which might be other endogenous proteins may be identified. In rabbits dead of anaphylactic shock following injection of bovine serum albumin, dense material was found within glomerular capillaries, presumably formed by the embolic deposition of antigen-antibody complexes, since the immunofluorescein and immunoferritin techniques demonstrated the presence of both BSA and rabbit globulin.     

Ehlers-Danlos syndrome type VIIA and VIIB result from splice-junction mutations or genomic deletions that involve exon 6 in the COL1A1 and COL1A2 genes of type I collagen

Ehlers-Danlos syndrome (EDS) type VII results from defects in the conversion of type I procollagen to collagen as a consequence of mutations in the substrate that alter the protease cleavage site (EDS type VIIA and VIIB) or in the protease itself (EDS type VIIC). We identified seven additional families in which EDS type VII is either dominantly inherited (one family with EDS type VIIB) or due to new dominant mutations (one family with EDS type VIIA and five families with EDS type VIIB). In six families, the mutations alter the consensus splice junctions, and, in the seventh family, the exon is deleted entirely. The COL1A1 mutation produced the most severe phenotypic effects, whereas those in the COL1A2 gene, regardless of the location or effect, produced congenital hip dislocation and other joint instability that was sometimes very marked. Fractures are seen in some people with EDS type VII, consistent with alterations in mineral deposition on collagen fibrils in bony tissues. These new findings expand the array of mutations known to cause EDS type VII and provide insight into genotype/phenotype relationships in these genes. Am. J. Med. Genet. 72:94–105, 1997. © 1997 Wiley-Liss, Inc.     

Comparison of the correlation of the Selvester QRS scoring system with cardiac contrast-enhanced magnetic resonance imaging-measured acute myocardial infarct size in patients with and without thrombolytic therapy

Background

After an acute myocardial infarction (MI), it is important to define the infarct size because it is related to mortality and morbidity. The Selvester QRS Score is an electrocardiographic (ECG) method that has been developed for estimating MI size. It has been shown to correlate well with postmortem anatomically measured sizes of single MI in patients who did not receive thrombolytic therapy. The aim of this study was to test the hypothesis that correlation between Selvester QRS Score-estimated MI size and contrast-enhanced magnetic resonance imaging (ceMRI)-measured MI size is equivalent in patients who did vs those who did not receive thrombolytic therapy.

Methods

Thirty-six patients with MI (24 with thrombolytic therapy and 12 without) received ceMRI and ECG at admission and at 1 or 6 months after admission. Indeed, in 23 of the patients, the therapy was intravenous only. The Selvester QRS Score was calculated using the 1-month ECG or, if not available, the 6-month ECG. The correlation between the 2 measures of MI size was determined for all patients and for the 2 groups separately.

Results

The mean MI size in the group that did not receive thrombolytic therapy was 8.5% ± 6.4% estimated by the Selvester QRS Score and 11.7% ± 10.2% measured by ceMRI. For the group that received thrombolytic therapy, Selvester QRS Score was 13.9% ± 11.1% and ceMRI was 20.2% ± 11.3%. The mean MI size in both groups combined was 12.1% ± 10.0% estimated by the Selvester QRS Score and 17.3% ± 11.5% measured by ceMRI. The Spearman rank correlation coefficient between Selvester QRS Score and ceMRI was 0.74 (P < .0001) for all patients, 0.74 (P < .0001) for the group that received thrombolytic therapy, and 0.64 (P = .024) for the group that did not receive thrombolytic therapy.

Conclusions

The associations between Selvester QRS Score and ceMRI-based MI were statistically significant and similar in both groups.     

Characterization of the oncogenic activity of the novel TRIM59 gene in mouse cancer models

A novel TRIM family member, TRIM59 gene was characterized to be upregulated in SV40 Tag oncogene-directed transgenic and knockout mouse prostate cancer models as a signaling pathway effector. We identified two phosphorylated forms of TRIM59 (p53 and p55) and characterized them using purified TRIM59 proteins from mouse prostate cancer models at different stages with wild-type mice and NIH3T3 cells as controls. p53/p55-TRIM59 proteins possibly represent Ser/Thr and Tyr phosphorylation modifications, respectively. Quantitative measurements by ELISA showed that the p-Ser/Thr TRIM59 correlated with tumorigenesis, whereas the p-Tyr-TRIM59 protein correlated with advanced cancer of the prostate (CaP). The function of TRIM59 was elucidated using short hairpin RNA (shRNA)-mediated knockdown of the gene in human CaP cells, which caused S-phase cell-cycle arrest and cell growth retardation. A hit-and-run effect of TRIM59 shRNA knockdown was observed 24 hours posttransfection. Differential cDNA microarrray analysis was conducted, which showed that the initial and rapid knockdown occurred early in the Ras signaling pathway. To confirm the proto-oncogenic function of TRIM59 in the Ras signaling pathway, we generated a transgenic mouse model using a prostate tissue-specific gene (PSP94) to direct the upregulation of the TRIM59 gene. Restricted TRIM59 gene upregulation in the prostate revealed the full potential for inducing tumorigenesis, similar to the expression of SV40 Tag, and coincided with the upregulation of genes specific to the Ras signaling pathway and bridging genes for SV40 Tag-mediated oncogenesis. The finding of a possible novel oncogene in animal models will implicate a novel strategy for diagnosis, prognosis, and therapy for cancer.