Detecting transmission and reassortment events for influenza A viruses with genotype profile method

Evolutionary events of transmission and reassortment for influenza A viruses were traditionally detected by phylogenetic analysis for influenza viruses' eight gene segments. Because the phylogenetic analysis can be complex, we developed genotype profile method which packaged the phylogenetic algorithms to analyze combination patterns of gene segments and integrated epidemiology knowledge. With the method, the analysis of reassortment and transmission becomes a simple and reliable process that combines genotypes, which is identical for the biological process of the virus. An application called IVEE that implements the method is available for all academic users to apply the method http://snptransformer.sourceforge.net. Furthermore, we found that a previous summary of the reassortment events in swine influenza A viruses may be inaccurate

Automated Quantification of Traffic Particulate Emissions via an Image Analysis Pipeline

Traffic emissions are known to contribute significantly to air pollution around the world, especially in heavily urbanized cities such as Singapore. It has been previously shown that the particulate pollution along major roadways exhibit strong correlation with increased traffic during peak hours, and that reductions in traffic emissions can lead to better health outcomes. However, in many instances, obtaining proper counts of vehicular traffic remains manual and extremely laborious. This then restricts one's ability to carry out longitudinal monitoring for extended periods, for example, when trying to understand the efficacy of intervention measures such as new traffic regulations (e.g. car-pooling) or for computational modelling. Hence, in this study, we propose and implement an integrated machine learning pipeline that utilizes traffic images to obtain vehicular counts that can be easily integrated with other measurements to facilitate various studies. We verify the utility and accuracy of this pipeline on an open-source dataset of traffic images obtained for a location in Singapore and compare the obtained vehicular counts with collocated particulate measurement data obtained over a 2-week period in 2022. The roadside particulate emission is observed to correlate well with obtained vehicular counts with a correlation coefficient of 0.93, indicating that this method can indeed serve as a quick and effective correlate of particulate emissions

Perilesional edema in radiation necrosis reflects axonal degeneration

BACKGROUND: Recently, we characterized a Gamma Knife® radiation necrosis mouse model with various magnetic resonance imaging (MRI) protocols to identify biomarkers useful in differentiation from tumors. Though the irradiation was focal to one hemisphere, a contralateral injury was observed that appeared to be localized in the white matter only. Interestingly, this injury was identifiable in T2-weighted images, apparent diffusion coefficient (ADC), and magnetization transfer ratio (MTR) maps, but not on post-contrast T1-weighted images. This observation of edema independent of vascular changes is akin to the perilesional edema seen in clinical radiation necrosis. FINDINGS: The pathology underlying the observed white-matter MRI changes was explored by performing immunohistochemistry for healthy axons and myelin. The presence of both healthy axons and myelin was reduced in the contralateral white-matter lesion. CONCLUSIONS: Based on our immunohistochemical findings, the contralateral white-matter injury is most likely due to axonal degeneration

Effect of Alkali-free Accelerator Containing Nano-silica on the Durability of Shotcrete

The effect of nano-silica-containing alkali-free accelerator and ordinary alkali-free accelerator on the durability of C30 shotcrete was investigated by means of seepage resistance tests and frost resistance tests. The results show that under the same conditions, the C30 shotcrete with nanosilica-containing alkali-free accelerator has a lower electrical flux and a greater impermeability rating than P10. The C30 shotcrete with nano-silica-containing alkali-free accelerator maintains a mass loss rate of about 0.4% after 200 freeze-thaw cycles, a 10.5% decrease in relative dynamic modulus of elasticity, a compressive strength loss rate of less than 20%, the bubble spacing coefficient and the average bubble diameter increased by 20.9% and 60.5% respectively, showing good frost resistance performance. This indicates that alkali-free accelerator containing nano-silica can improve the durability of shotcrete. In addition, a comparison was also made between ordinary accelerator shotcrete with nano-silica, and when 5% nano-silica was added, the properties of shotcrete were comparable to those of 2% nano-silica alkali-free accelerator shotcrete

Correlation of pain with substance P and neurokinin-1 receptor in the L5–S2 spinal cord in rats with chronic nonbacterial prostatitis

The incidence of prostate pain is 90%–95% in prostatitis. The symptoms are persistent, which is prone to relapse and difficult to be cured. It seriously affects the survival and quality of life of patients. This study analyzed the correlation between pain and substance P (SP) and neurokinin-1 receptors (NK-1R) in the L5–S2 spinal cord of chronic nonbacterial prostatitis (CNP) rats, which may give a new way to explore the pathogenesis and treatment of pain in prostatitis. We randomly divided the rats into control group, 45 d group, 60 d group, and 90 d group. After making a rat model with autoimmune method, the paw withdrawal threshold (PWT) was measured, the histomorphological changes in the prostate was observed by transmission electron microscopy and light microscopy. The expression of SP and NK-1R was measured by immunohistochemistry, and the concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), and interleukin-10 (IL-10) were measured by enzyme linked immunosorbent assay (ELISA). Compared with the control group, the PWT was decreased by 34.21%, 41.90% and 64.79%, TNF-α was increased by 74.19%, 89.45% and 132.15%, IL-1β was increased by 148.88%, 181.95% and 250.74%, IL-2 was increased by 75.97%, 82.15% and 128.57% and IL-10 was increased by 31.04%, 63.28% and 212.99% in the 45 d group, 60 d group and 90 d group respectively. Microscope observation showed the structure of prostate tissue in control group was normal. However, the prostate tissue had obvious inflammatory response with the model extension. The expressions of SP and NK-1R in each model group were significantly higher than the control group. There was a significant correlation between pain and SP in L5–S2 spinal cord in CNP rats. These findings are indicative of a correlation between pain and the expression levels of SP and NK-1R in the L5–S2 spinal cord of CNP rats

Human DNA Exonuclease TREX1 Is Also an Exoribonuclease That Acts on Single-Stranded RNA

3\u27 repair exonuclease 1 (TREX1) is a known DNA exonuclease involved in autoimmune disorders and the antiviral response. In this work, we show that TREX1 is also a RNA exonuclease. Purified TREX1 displays robust exoribonuclease activity that degrades single-stranded, but not double-stranded, RNA. TREX1-D200N, an Aicardi-Goutieres syndrome disease-causing mutant, is defective in degrading RNA. TREX1 activity is strongly inhibited by a stretch of pyrimidine residues as is a bacterial homolog, RNase T. Kinetic measurements indicate that the apparent Km of TREX1 for RNA is higher than that for DNA. Like RNase T, human TREX1 is active in degrading native tRNA substrates. Previously reported TREX1 crystal structures have revealed that the substrate binding sites are open enough to accommodate the extra hydroxyl group in RNA, further supporting our conclusion that TREX1 acts on RNA. These findings indicate that its RNase activity needs to be taken into account when evaluating the physiological role of TREX1

Distinguishing tumor admixed in a radiation necrosis (RN) background: 1H and 2H MR with a novel mouse brain-tumor/RN model

PURPOSE: Distinguishing radiation necrosis (RN) from recurrent tumor remains a vexing clinical problem with important health-care consequences for neuro-oncology patients. Here, mouse models of pure tumor, pure RN, and admixed RN/tumor are employed to evaluate hydrogen ( MATERIALS AND METHODS: A pipeline of common quantitative RESULTS: Differences in quantitative CONCLUSIONS: These findings, employing a pipeline of quantitativ

Identification and Characterization of \u3cem\u3eOGG1\u3c/em\u3e Mutations in Patients with Alzheimer\u27s Disease

Patients with Alzheimer\u27s disease (AD) exhibit higher levels of 8-oxo-guanine (8-oxoG) DNA lesions in their brain, suggesting a reduced or defective 8-oxoG repair. To test this hypothesis, this study investigated 14 AD patients and 10 age-matched controls for mutations of the major 8-oxoG removal gene OGG1. Whereas no alterations were detected in any control samples, four AD patients exhibited mutations in OGG1, two carried a common single base (C796) deletion that alters the carboxyl terminal sequence of OGG1, and the other two had nucleotide alterations leading to single amino acid substitutions. In vitro biochemical assays revealed that the protein encoded by the C796-deleted OGG1 completely lost its 8-oxoG glycosylase activity, and that the two single residue-substituted OGG1 proteins showed a significant reduction in the glycosylase activity. These results were consistent with the fact that nuclear extracts derived from a limited number of AD patients with OGG1 mutations exhibited greatly reduced 8-oxoG glycosylase activity compared with age-matched controls and AD patients without OGG1 alterations. Our findings suggest that defects in OGG1 may be important in the pathogenesis of AD in a significant fraction of AD patients and provide new insight into the molecular basis for the disease

Pan-Pathway Based Interaction Profiling of FDA-Approved Nucleoside and Nucleobase Analogs with Enzymes of the Human Nucleotide Metabolism

To identify interactions a nucleoside analog library (NAL) consisting of 45 FDA-approved nucleoside analogs was screened against 23 enzymes of the human nucleotide metabolism using a thermal shift assay. The method was validated with deoxycytidine kinase; eight interactions known from the literature were detected and five additional interactions were revealed after the addition of ATP, the second substrate. The NAL screening gave relatively few significant hits, supporting a low rate of “off target effects.” However, unexpected ligands were identified for two catabolic enzymes guanine deaminase (GDA) and uridine phosphorylase 1 (UPP1). An acyclic guanosine prodrug analog, valaciclovir, was shown to stabilize GDA to the same degree as the natural substrate, guanine, with a ΔTagg around 7°C. Aciclovir, penciclovir, ganciclovir, thioguanine and mercaptopurine were also identified as ligands for GDA. The crystal structure of GDA with valaciclovir bound in the active site was determined, revealing the binding of the long unbranched chain of valaciclovir in the active site of the enzyme. Several ligands were identified for UPP1: vidarabine, an antiviral nucleoside analog, as well as trifluridine, idoxuridine, floxuridine, zidovudine, telbivudine, fluorouracil and thioguanine caused concentration-dependent stabilization of UPP1. A kinetic study of UPP1 with vidarabine revealed that vidarabine was a mixed-type competitive inhibitor with the natural substrate uridine. The unexpected ligands identified for UPP1 and GDA imply further metabolic consequences for these nucleoside analogs, which could also serve as a starting point for future drug design