The impact of model detail on power grid resilience measures

Peer reviewedPreprin

The Emerging Role of Two-Pore Domain Potassium Channels in Breast Cancer

Potassium ion channels are transmembrane proteins that selectively facilitate ion flow down an electrochemical gradient between intracellular and extracellular environments. There is accumulating evidence which suggest that potassium channel protein activity is important in the pathophysiology of cancer, and associations of the two-pore domain family of potassium channels and breast cancer are currently emerging. The aim of this review is to summarize data on mechanisms of action related to oncogenic properties and examine the role of the two-pore domain family in breast cancer

FUNCTIONAL DIVERGENCE OF DUPLICATED GENES IN THE SOYBEAN GENOME

The soybean genome has undergone many different evolutionary changes that are observable with modern technologies. Of particular interest to scientists and plant breeders is the fact that the soybean genome exhibits features of genome duplication from millions of years ago. Genes that were copied during the duplication event have since diverged functionally. Identifying functionally divergent duplicate genes may provide insight into the evolution of soybean. To investigate functional divergence, transcripts from seven different tissue samples of pooled soybean messenger RNA were sequenced using the Solexa next-generation sequencer and analyzed for gene expression. We tested differential expression of duplicated genes within tissue by employing an integrated normalization and statistical testing methodology. Blocks of duplicate genes (i.e., gene sets) were tested for unanimity of over-or under-expression. These same genes were also analyzed for differential expression across tissues. We identified thousands of duplicate genes that displayed differential expression patterns within each tissue. In some cases these genes were over-represented in duplicate blocks, suggestive of functional divergence of a large genomic region

STATISTICAL ISSUES IN NEXT-GENERATION SEQUENCING

High throughput deep-sequencing or next-generation sequencing has emerged as an exciting new tool in a great number of applications (e.g., variant discovery, profiling of histone modifications, identifying transcription factor binding sites, resequencing, and transcriptome characterization). Even though this technology has generated unprecedented amounts of data in the scientific community few studies have looked carefully at its inherent variability. Recent studies of mRNA expression levels found little appreciable technical variation in Illumina’s Solexa sequencing platform (a next-generation sequencing device). Although these results are encouraging, they are limited to a specific platform and application, and have been made without any attention to experimental design. This paper provides an overview of some key issues in data management and experimental design related to Illumina’s Solexa Genome Analyzer technology

Death and transfiguration in static staphylococcus epidermidis cultures

The overwhelming majority of bacteria live in slime embedded microbial communities termed biofilms, which are typically adherent to a surface. However, when several Staphylococcus epidermidis strains were cultivated in static liquid cultures, macroscopic aggregates were seen floating within the broth and also sedimented at the test tube bottom. Light- and electron microscopy revealed that early-stage aggregates consisted of bacteria and extracellular matrix, organized in sheetlike structures. Perpendicular under the sheets hung a network of periodically arranged, bacteria-associated strands. During the extended cultivation, the strands of a subpopulation of aggregates developed into cross-connected wall-like structures, in which aligned bacteria formed the walls. The resulting architecture had a compartmentalized appearance. In late-stage cultures, the wall-associated bacteria disintegrated so that, henceforth, the walls were made of the coalescing remnants of lysed bacteria, while the compartment-like organization remained intact. At the same time, the majority of strand containing aggregates with associated culturable bacteria continued to exist. These observations indicate that some strains of Staphylococcus epidermidis are able to build highly sophisticated structures, in which a subpopulation undergoes cell lysis, presumably to provide continued access to nutrients in a nutrient-limited environment, whilst maintaining structural integrity

α-Adrenergic inhibition of proliferation in HepG2 cells stably transfected with the α1B-adrenergic receptor through a p42MAP kinase/p21Cip1/WAF1-dependent pathway

AbstractActivation of α1B adrenergic receptors (α1BAR) promotes DNA synthesis in primary cultures of hepatocytes, yet expression of α1BAR in hepatocytes rapidly declines during proliferative events. HepG2 human hepatoma cells, which do not express α1BAR, were stably transfected with a rat α1BAR cDNA (TFG2 cells), in order to study the effects of maintained α1BAR expression on hepatoma cell proliferation. TFG2 cells had a decreased rate of growth compared to mock transfected HepG2 cells as revealed by a decrease in [3H]thymidine incorporation into DNA. Stimulation of α1BAR with phenylephrine caused a further large reduction in TFG2 cell growth, whereas no effect on growth was observed in mock transfected cells. Reduced cell growth correlated with increased percentages of cells found in G0/G1 and G2/M phases of the cell cycle. In TFG2 cells, phenylephrine increased p42MAP kinase activity by 1.5- to 2.0-fold for up to 24 h and increased expression of the cyclin dependent kinase inhibitor protein p21Cip1/WAF1. Treatment of TFG2 cells with the specific MEK1 inhibitor PD98059, or infection with a −/− MEK1 recombinant adenovirus permitted phenylephrine to increase rather than decrease [3H]thymidine incorporation. In addition, inhibition of MAP kinase signaling by PD98059 or MEK1 −/− blunted the ability of phenylephrine to increase p21Cip1/WAF1 expression. In agreement with a role for increased p21Cip1/WAF1 expression in causing growth arrest, infection of TFG2 cells with a recombinant adenovirus to express antisense p21Cip1/WAF1 mRNA blocked the ability of phenylephrine to increase p21Cip1/WAF1 expression and to inhibit DNA synthesis. Antisense p21Cip1/WAF1 permitted phenylephrine to stimulate DNA synthesis in TFG2 cells, and abrogated growth arrest. These results suggest that transformed hepatocytes may turn off the expression of α1BARs in order to prevent the activation of a growth inhibitory pathway. Activation of this inhibitory pathway via α1BAR appears to be p42MAP kinase and p21Cip1/WAF1 dependent

Altered nucleus basalis connectivity predicts treatment response in mild cognitive impairment

Purpose: To determine whether functional connectivity (FC) mapping of nucleus basalis of Meynert (NBM) cholinergic network (hereafter, NBM FC) could provide a biomarker of central cholinergic deficits with predictive potential for response to cholinesterase inhibitor (ChEI) treatment.Materials and Methods: The Alzheimer’s Disease Neuroimaging Initiative (ADNI) was approved by the institutional review boards of all participating sites. All participants and their representatives gave written informed consent prior to data collection. NBM FC was examined in 33 healthy control participants, 102 patients with mild cognitive impairment (MCI), and 33 patients with AD by using resting-state functional MRI data from the ADNI database. NBM FC was compared between groups before and after 6 months of ChEI treatment in MCI. Associations between baseline NBM FC and baseline cognitive performance as well as cognitive outcomes after treatment were investigated.Results: Compared with the healthy control group, NBM FC was decreased in patients with untreated MCI and increased in patients with AD treated with ChEI (corrected P ˂ .05). Global cognition (Alzheimer’s Disease Assessment Scale-Cognitive subscale score) was associated with NBM FC (r = −0.349; P ˂ .001). NBM FC was higher 6 months after ChEI compared with before ChEI in treated MCI (corrected P ˂ .05), but did not change at 6 months in patients with untreated MCI (corrected P ˂ .05). Baseline NBM FC in MCI strongly predicted cognitive outcomes 6 months after ChEI (R2 = 0.458; P = .001).Conclusion: Functional dissociation of the nucleus basalis of Meynert from a cortical network may explain the cognitive deficits in dementia and allow for the selection of individuals who are more likely to respond to cholinesterase inhibitors at early disease stages

The Search for Supernova-produced Radionuclides in Terrestrial Deep-sea Archives

An enhanced concentration of 60Fe was found in a deep ocean's crust in 2004 in a layer corresponding to an age of ~2 Myr. The confirmation of this signal in terrestrial archives as supernova-induced and detection of other supernova-produced radionuclides is of great interest. We have identified two suitable marine sediment cores from the South Australian Basin and estimated the intensity of a possible signal of the supernova-produced radionuclides 26Al, 53Mn, 60Fe and the pure r-process element 244Pu in these cores. A finding of these radionuclides in a sediment core might allow to improve the time resolution of the signal and thus to link the signal to a supernova event in the solar vicinity ~2 Myr ago. Furthermore, it gives an insight on nucleosynthesis scenarios in massive stars, the condensation into dust grains and transport mechanisms from the supernova shell into the solar system

Activation induced changes in GABA: functional MRS at 7 T with MEGA-sLASER

Functional magnetic resonance spectroscopy (fMRS) has been used to assess the dynamic metabolic responses of the brain to a physiological stimulus non-invasively. However, only limited information on the dynamic functional response of γ-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain, is available. We aimed to measure the activation-induced changes in GABA unambiguously using a spectral editing method, instead of the conventional direct detection techniques used in previous fMRS studies. The Mescher-Garwood-semi-localised by adiabatic selective refocusing (MEGA-sLASER) sequence was developed at 7 T to obtain the time course of GABA concentration without macromolecular contamination. A significant decrease (−12±5%) in the GABA to total creatine ratio (GABA/tCr) was observed in the motor cortex during a period of 10 minutes of hand-clenching, compared to an initial baseline level (GABA/tCr = 0.11±0.02) at rest. An increase in the Glx (glutamate and glutamine) to tCr ratio was also found, which is in agreement with previous findings. In contrast, no significant changes in NAA/tCr and tCr were detected. With consistent and highly efficient editing performance for GABA detection and the advantage of visually identifying GABA resonances in the spectra, MEGA-sLASER is demonstrated to be an effective method for studying of dynamic changes in GABA at 7 T