Effect of varying skin surface electrode position on electroretinogram responses recorded using a handheld stimulating and recording system

Purpose A handheld device (the RETeval system, LKC Technologies) aims to increase the ease of electroretinogram (ERG) recording by using specially designed skin electrodes, rather than corneal electrodes. We explored effects of electrode position on response parameters recorded using this device. Methods Healthy adult twins were recruited from the TwinsUK cohort and underwent recording of light-adapted flicker ERGs (corresponding to international standard stimuli). In Group 1, skin electrodes were placed in a “comfortable” position, which was up to 20 mm below the lid margin. For subsequent participants (Group 2), the electrode was positioned 2 mm from the lid margin as recommended by the manufacturer. Amplitudes and peak times (averaged from both eyes) were compared between groups after age-matching and inclusion of only one twin per pair. Light-adapted flicker and flash ERGs were recorded for an additional 10 healthy subjects in two consecutive recording sessions: in the test eye, electrode position was varied from 2 to 10–20 mm below the lid margin between sessions; in the fellow (control) eye, the electrode was 2 mm below the lid margin throughout. Amplitudes and peak times (test eye normalised to control eye) were compared for the two sessions. Results Including one twin per pair, and age-matching yielded 28 individuals per group. Flicker ERG amplitudes were significantly lower for Group 1 than Group 2 participants (p = 0.0024). However, mean peak times did not differ between groups (p = 0.54). For the subjects in whom electrode position was changed between recording sessions, flash and flicker amplitudes were significantly lower when positioned further from the lid margin (p  0.5). Conclusions Moving the skin electrodes further from the lid margin significantly reduces response amplitudes, highlighting the importance of consistent electrode positioning. However, this does not significantly affect peak times. Thus, it may be feasible to adopt a more comfortable position in participants who cannot tolerate the recommended position if analysis is restricted to peak time parameters

p16 Overexpression: A Potential Early Indicator of Transformation in Ovarian Carcinoma

Objective: The recently cloned gene p16 (MST 1) has been identified as a putative tumor suppressor gene that binds to CDK4 and CDK6 (cyclin-dependent kinases), preventing their interaction with cyclin D1 and thereby preventing cell cycle progression at the G1 stage. In addition, the p16 gene has been shown to have a high frequency of mutation in some tumor cell lines; however, it has also been shown that a much lower frequency of mutation occurs in primary tumors. This study investigated the mRNA expression level and mutation status of the p16 gene in ovarian tumors. Methods: We performed quantitative polymerase chain reaction and direct cDNA sequencing analysis. To confirm the p16 protein level in ovarian tumors, Western blotting and immunohistochemical staining were performed. Expression levels of mRNA for the p16 gene relative to the β-tubulin gene were examined in 32 ovarian tumors (24 carcinomas, six low malignant potential tumors, and two benign tumors) and six normal ovaries. Results: The mRNA expression level of p16 was significantly elevated in 28 ovarian tumors (22 carcinomas, five low malignant potential tumors, and one benign tumor) compared with that of normal ovaries. Western blotting analysis and immunohistochemical staining confirmed elevated p16 protein levels in ovarian tumor samples. Among 32 ovarian tumors, cDNA sequencing of the p16 gene showed no p16 mutation resulting in a coding error, although one silent mutation and three polymorphisms were found. Conclusions: Although p16 is seldom mutated in ovarian tumors, the overexpression of p16 in most ovarian tumor cases indicates a dysfunction in the regulatory complex for G1 arrest. Therefore, overexpression of p16 may be an important early event in the neoplastic transformation of the ovarian epithelium.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68382/2/10.1177_107155769700400209.pd

Angiostatin anti-angiogenesis requires IL-12: The innate immune system as a key target

© 2009 Albini et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Complete Genome Sequence of Treponema paraluiscuniculi, Strain Cuniculi A: The Loss of Infectivity to Humans Is Associated with Genome Decay

Treponema paraluiscuniculi is the causative agent of rabbit venereal spirochetosis. It is not infectious to humans, although its genome structure is very closely related to other pathogenic Treponema species including Treponema pallidum subspecies pallidum, the etiological agent of syphilis. In this study, the genome sequence of Treponema paraluiscuniculi, strain Cuniculi A, was determined by a combination of several high-throughput sequencing strategies. Whereas the overall size (1,133,390 bp), arrangement, and gene content of the Cuniculi A genome closely resembled those of the T. pallidum genome, the T. paraluiscuniculi genome contained a markedly higher number of pseudogenes and gene fragments (51). In addition to pseudogenes, 33 divergent genes were also found in the T. paraluiscuniculi genome. A set of 32 (out of 84) affected genes encoded proteins of known or predicted function in the Nichols genome. These proteins included virulence factors, gene regulators and components of DNA repair and recombination. The majority (52 or 61.9%) of the Cuniculi A pseudogenes and divergent genes were of unknown function. Our results indicate that T. paraluiscuniculi has evolved from a T. pallidum-like ancestor and adapted to a specialized host-associated niche (rabbits) during loss of infectivity to humans. The genes that are inactivated or altered in T. paraluiscuniculi are candidates for virulence factors important in the infectivity and pathogenesis of T. pallidum subspecies

MicroRNA Expression Characterizes Oligometastasis(es)

Cancer staging and treatment presumes a division into localized or metastatic disease. We proposed an intermediate state defined by ≤ 5 cumulative metastasis(es), termed oligometastases. In contrast to widespread polymetastases, oligometastatic patients may benefit from metastasis-directed local treatments. However, many patients who initially present with oligometastases progress to polymetastases. Predictors of progression could improve patient selection for metastasis-directed therapy.Here, we identified patterns of microRNA expression of tumor samples from oligometastatic patients treated with high-dose radiotherapy.Patients who failed to develop polymetastases are characterized by unique prioritized features of a microRNA classifier that includes the microRNA-200 family. We created an oligometastatic-polymetastatic xenograft model in which the patient-derived microRNAs discriminated between the two metastatic outcomes. MicroRNA-200c enhancement in an oligometastatic cell line resulted in polymetastatic progression.These results demonstrate a biological basis for oligometastases and a potential for using microRNA expression to identify patients most likely to remain oligometastatic after metastasis-directed treatment

The plasma environment of comet 67P/Churyumov-Gerasimenko

The environment of a comet is a fascinating and unique laboratory to study plasma processes and the formation of structures such as shocks and discontinuities from electron scales to ion scales and above. The European Space Agency’s Rosetta mission collected data for more than two years, from the rendezvous with comet 67P/Churyumov-Gerasimenko in August 2014 until the final touch-down of the spacecraft end of September 2016. This escort phase spanned a large arc of the comet’s orbit around the Sun, including its perihelion and corresponding to heliocentric distances between 3.8 AU and 1.24 AU. The length of the active mission together with this span in heliocentric and cometocentric distances make the Rosetta data set unique and much richer than sets obtained with previous cometary probes. Here, we review the results from the Rosetta mission that pertain to the plasma environment. We detail all known sources and losses of the plasma and typical processes within it. The findings from in-situ plasma measurements are complemented by remote observations of emissions from the plasma. Overviews of the methods and instruments used in the study are given as well as a short review of the Rosetta mission. The long duration of the Rosetta mission provides the opportunity to better understand how the importance of these processes changes depending on parameters like the outgassing rate and the solar wind conditions. We discuss how the shape and existence of large scale structures depend on these parameters and how the plasma within different regions of the plasma environment can be characterised. We end with a non-exhaustive list of still open questions, as well as suggestions on how to answer them in the future

Both Positive and Negative Selection Pressures Contribute to the Polymorphism Pattern of the Duplicated Human CYP21A2 Gene.

The human steroid 21-hydroxylase gene (CYP21A2) participates in cortisol and aldosterone biosynthesis, and resides together with its paralogous (duplicated) pseudogene in a multiallelic copy number variation (CNV), called RCCX CNV. Concerted evolution caused by non-allelic gene conversion has been described in great ape CYP21 genes, and the same conversion activity is responsible for a serious genetic disorder of CYP21A2, congenital adrenal hyperplasia (CAH). In the current study, 33 CYP21A2 haplotype variants encoding 6 protein variants were determined from a European population. CYP21A2 was shown to be one of the most diverse human genes (HHe=0.949), but the diversity of intron 2 was greater still. Contrary to previous findings, the evolution of intron 2 did not follow concerted evolution, although the remaining part of the gene did. Fixed sites (different fixed alleles of sites in human CYP21 paralogues) significantly accumulated in intron 2, indicating that the excess of fixed sites was connected to the lack of effective non-allelic conversion and concerted evolution. Furthermore, positive selection was presumably focused on intron 2, and possibly associated with the previous genetic features. However, the positive selection detected by several neutrality tests was discerned along the whole gene. In addition, the clear signature of negative selection was observed in the coding sequence. The maintenance of the CYP21 enzyme function is critical, and could lead to negative selection, whereas the presumed gene regulation altering steroid hormone levels via intron 2 might help fast adaptation, which broadly characterizes the genes of human CNVs responding to the environment

Biogenesis and functions of bacterial S-layers.

The outer surface of many archaea and bacteria is coated with a proteinaceous surface layer (known as an S-layer), which is formed by the self-assembly of monomeric proteins into a regularly spaced, two-dimensional array. Bacteria possess dedicated pathways for the secretion and anchoring of the S-layer to the cell wall, and some Gram-positive species have large S-layer-associated gene families. S-layers have important roles in growth and survival, and their many functions include the maintenance of cell integrity, enzyme display and, in pathogens and commensals, interaction with the host and its immune system. In this Review, we discuss our current knowledge of S-layer and related proteins, including their structures, mechanisms of secretion and anchoring and their diverse functions

Global reward state affects learning and activity in raphe nucleus and anterior insula in monkeys

202009 bcrcVersion of RecordPublishe