Accelerating DNA Computing via PLP-qPCR Answer Read out to Solve Traveling Salesman Problems

An asymmetric, fully-connected 8-city traveling salesman problem (TSP) was solved by DNA computing using the ordered node pair abundance (ONPA) approach through the use of pair ligation probe quantitative real time polymerase chain reaction (PLP-qPCR). The validity of using ONPA to derive the optimal answer was confirmed by in silico computing using a reverse-engineering method to reconstruct the complete tours in the feasible answer set from the measured ONPA. The high specificity of the sequence-tagged hybridization, and ligation that results from the use of PLPs significantly increased the accuracy of answer determination in DNA computing. When combined with the high throughput efficiency of qPCR, the time required to identify the optimal answer to the TSP was reduced from days to 25 min

Carrier dynamics in α‐Fe2O3 (0001) thin films and single crystals probed by femtosecond transient absorption and reflectivity

Femtosecond transient reflectivity and absorption are used to measure the carrier lifetimes in α‐Fe2O3 thin films and single crystals. The results from the thin films show that initially excited hot electrons relax to the band edge within 300 fs and then recombine with holes or trap within 5 ps. The trapped electrons have a lifetime of hundreds of picoseconds. Transient reflectivity measurements from hematite (α‐Fe2O3)single crystals show similar but slightly faster dynamics leading to the conclusion that the short carrier lifetimes in these materials are due primarily to trapping to Fe d-d states in the band gap. In the hematite single crystal, the transient reflectivity displays oscillations due to the formation of longitudinal acoustic phonons generated following absorption of the ultrashort excitation pulse

Murine roseolovirus does not accelerate amyloid-β pathology and human roseoloviruses are not over-represented in Alzheimer disease brains

BACKGROUND: The role of viral infection in Alzheimer Disease (AD) pathogenesis is an area of great interest in recent years. Several studies have suggested an association between the human roseoloviruses, HHV-6 and HHV-7, and AD. Amyloid-β (Aβ) plaques are a hallmark neuropathological finding of AD and were recently proposed to have an antimicrobial function in response to infection. Identifying a causative and mechanistic role of human roseoloviruses in AD has been confounded by limitations in performing in vivo studies. Recent -omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Murine roseolovirus (MRV) is a natural murine pathogen that is highly-related to the human roseoloviruses, providing an opportunity to perform well-controlled studies of the impact of roseolovirus on Aβ deposition. METHODS: We utilized the 5XFAD mouse model to test whether MRV induces Aβ deposition in vivo. We also evaluated viral load and neuropathogenesis of MRV infection. To evaluate Aβ interaction with MRV, we performed electron microscopy. RNA-sequencing of a cohort of AD brains compared to control was used to investigate the association between human roseolovirus and AD. RESULTS: We found that 5XFAD mice were susceptible to MRV infection and developed neuroinflammation. Moreover, we demonstrated that Aβ interacts with viral particles in vitro and, subsequent to this interaction, can disrupt infection. Despite this, neither peripheral nor brain infection with MRV increased or accelerated Aβ plaque formation. Moreover, -omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Our RNA-sequencing analysis of a cohort of AD brains compared to controls did not show an association between roseolovirus infection and AD. CONCLUSION: Although MRV does infect the brain and cause transient neuroinflammation, our data do not support a role for murine or human roseoloviruses in the development of Aβ plaque formation and AD

Carisbamate Blockade of T-Type Voltage-Gated Calcium Channels

Objectives Carisbamate (CRS) is a novel monocarbamate compound that possesses antiseizure and neuroprotective properties. However, the mechanisms underlying these actions remain unclear. Here, we tested both direct and indirect effects of CRS on several cellular systems that regulate intracellular calcium concentration [Ca2+]i. Methods We used a combination of cellular electrophysiologic techniques, as well as cell viability, Store Overload‐Induced Calcium Release (SOICR), and mitochondrial functional assays to determine whether CRS might affect [Ca2+]i levels through actions on the endoplasmic reticulum (ER), mitochondria, and/or T‐type voltage‐gated Ca2+ channels. Results In CA3 pyramidal neurons, kainic acid induced significant elevations in [Ca2+]i and long‐lasting neuronal hyperexcitability, both of which were reversed in a dose‐dependent manner by CRS. Similarly, CRS suppressed spontaneous rhythmic epileptiform activity in hippocampal slices exposed to zero‐Mg2+ or 4‐aminopyridine. Treatment with CRS also protected murine hippocampal HT‐22 cells against excitotoxic injury with glutamate, and this was accompanied by a reduction in [Ca2+]i. Neither kainic acid nor CRS alone altered the mitochondrial membrane potential (ΔΨ) in intact, acutely isolated mitochondria. In addition, CRS did not affect mitochondrial respiratory chain activity, Ca2+‐induced mitochondrial permeability transition, and Ca2+ release from the ER. However, CRS significantly decreased Ca2+ flux in human embryonic kidney tsA‐201 cells transfected with Cav3.1 (voltage‐dependent T‐type Ca2+) channels. Significance Our data indicate that the neuroprotective and antiseizure activity of CRS likely results in part from decreased [Ca2+]i accumulation through blockade of T‐type Ca2+ channels

Single-feature polymorphism discovery by computing probe affinity shape powers

<p>Abstract</p> <p>Background</p> <p>Single-feature polymorphism (SFP) discovery is a rapid and cost-effective approach to identify DNA polymorphisms. However, high false positive rates and/or low sensitivity are prevalent in previously described SFP detection methods. This work presents a new computing method for SFP discovery.</p> <p>Results</p> <p>The probe affinity differences and affinity shape powers formed by the neighboring probes in each probe set were computed into SFP weight scores. This method was validated by known sequence information and was comprehensively compared with previously-reported methods using the same datasets. A web application using this algorithm has been implemented for SFP detection. Using this method, we identified 364 SFPs in a barley near-isogenic line pair carrying either the wild type or the mutant <it>uniculm2 </it>(<it>cul2</it>) allele. Most of the SFP polymorphisms were identified on chromosome 6H in the vicinity of the <it>Cul2 </it>locus.</p> <p>Conclusion</p> <p>This SFP discovery method exhibits better performance in specificity and sensitivity over previously-reported methods. It can be used for other organisms for which GeneChip technology is available. The web-based tool will facilitate SFP discovery. The 364 SFPs discovered in a barley near-isogenic line pair provide a set of genetic markers for fine mapping and future map-based cloning of the <it>Cul2 </it>locus.</p

Identification of Close Relatives in the HUGO Pan-Asian SNP Database

The HUGO Pan-Asian SNP Consortium has recently released a genome-wide dataset, which consists of 1,719 DNA samples collected from 71 Asian populations. For studies of human population genetics such as genetic structure and migration history, this provided the most comprehensive large-scale survey of genetic variation to date in East and Southeast Asia. However, although considered in the analysis, close relatives were not clearly reported in the original paper. Here we performed a systematic analysis of genetic relationships among individuals from the Pan-Asian SNP (PASNP) database and identified 3 pairs of monozygotic twins or duplicate samples, 100 pairs of first-degree and 161 second-degree of relationships. Three standardized subsets with different levels of unrelated individuals were suggested here for future applications of the samples in most types of population-genetics studies (denoted by PASNP1716, PASNP1640 and PASNP1583 respectively) based on the relationships inferred in this study. In addition, we provided gender information for PASNP samples, which were not included in the original dataset, based on analysis of X chromosome data