Cockayne Syndrome Linked to Elevated R-Loops Induced by Stalled RNA Polymerase II during Transcription Elongation

Mutations in the Cockayne Syndrome group B (CSB) gene cause cancer in mice, but premature aging and severe neurodevelopmental defects in humans. CSB, a member of the SWI/SNF family of chromatin remodelers, plays diverse roles in regulating gene expression and transcription-coupled nucleotide excision repair (TC-NER); however, these functions do not explain the distinct phenotypic differences observed between CSB-deficient mice and humans. During investigating Cockayne Syndrome-associated genome instability, we uncover an intrinsic mechanism that involves elongating RNA polymerase II (RNAPII) undergoing transient pauses at internal T-runs where CSB is required to propel RNAPII forward. Consequently, CSB deficiency retards RNAPII elongation in these regions, and when coupled with G-rich sequences upstream, exacerbates genome instability by promoting R-loop formation. These R-loop prone motifs are notably abundant in relatively long genes related to neuronal functions in the human genome, but less prevalent in the mouse genome. These findings provide mechanistic insights into differential impacts of CSB deficiency on mice versus humans and suggest that the manifestation of the Cockayne Syndrome phenotype in humans results from the progressive evolution of mammalian genomes

Extremely discrepant mutation spectrum of SLC26A4 between Chinese patients with isolated Mondini deformity and enlarged vestibular aqueduct

<p>Abstract</p> <p>Background</p> <p>Mutations in <it>SLC26A4 </it>cause Pendred syndrome (hearing loss with goiter) or DFNB4 (non-syndromic hearing loss with inner ear malformation, such as enlarged vestibular aqueduct or Mondini deformity). The relationship between mutations in <it>SLC26A4 </it>and Mondini deformity without enlarged vestibular aqueduct has not been studied in any Chinese deaf population. The purpose of this study was to assess whether mutations in the <it>SLC26A4 </it>gene cause Mondini deformity without an enlarged vestibular aqueduct (isolated Mondini deformity) in a Chinese population.</p> <p>Methods</p> <p>In total, 144 patients with sensorineural hearing loss were included and subjected to high-resolution temporal bone CT. Among them, 28 patients with isolated Mondini dysplasia (MD group), 50 patients with enlarged vestibular aqueduct with Mondini dysplasia (EVA with MD group), 50 patients with enlarged vestibular aqueduct without Mondini dysplasia (EVA group), and 16 patients with other types of inner ear malformations (IEM group) were identified. The coding exons of <it>SLC26A4 </it>were analyzed in all subjects.</p> <p>Results</p> <p>DNA sequence analysis of <it>SLC26A4 </it>was performed in all 144 patients. In the different groups, the detection rate of the <it>SLC26A4 </it>mutation differed. In the isolated MD group, only one single allelic mutation in <it>SLC26A4 </it>was found in one patient (1/28, 3.6%). In the EVA with MD group, biallelic and monoallelic <it>SLC26A4 </it>mutations were identified in 46 patients (46/50, 92.0%) and three patients (3/50, 6.0%), respectively. Also, in the EVA group, biallelic and monoallelic <it>SLC26A4 </it>mutations were identified in 46 patients (46/50, 92.0%) and three patients (3/50, 6.0%), respectively. These percentages were identical to those in the EVA plus MD group. Only two patients carried monoallelic mutations of the <it>SLC26A4 </it>gene in the IEM group (2/16, 12.5%). There were significant differences in the frequency of <it>SLC26A4 </it>mutation among the groups (P < 0.001). The detection rate of <it>SLC26A4 </it>mutation in the isolated MD group was significantly lower than in the EVA group (with or without MD; P < 0.001), and there was no significant difference in the detection rate of <it>SLC26A4 </it>between the MD group and IEM group (P > 0.5).</p> <p>Conclusion</p> <p>Although mutations in the <it>SLC26A4 </it>gene were frequently found in Chinese EVA patients with and without MD, there was no evidence to show a relationship between isolated MD and the <it>SLC26A4 </it>gene in the Chinese population examined. Hearing impairment in patients with isolated MD may be caused by factors other than mutations in the <it>SLC26A4 </it>gene.</p

Acoustofluidics along inclined surfaces based on AlN/Si Rayleigh surface acoustic waves

Conventional acoustofluidics are restricted to manipulation of droplets on a flat surface, and there is an increasing demand for acoustofluidic devices to be performed at inclined surfaces to facilitate multilayered microfluidic device design and enhance system compactness. This paper reports theoretical and experimental studies of acoustofluidic behaviors (including transportation/pumping and jetting) along inclined surfaces using AlN/Si Rayleigh surface acoustic waves (SAWs). It has been demonstrated that for droplets with volume smaller than 3 μL, they could be efficiently transported on arbitrary inclined surfaces. The gravity effect would play a more and more important role in uphill climbing with the increased inclination angle. When the inclination angle was increased up to 90°, a higher threshold power was needed to transport the droplet and the maximum droplet volume which can be pumped also reached its minimum value. Effects of surface inclination angle on droplet jetting angles could be neglected for their volumes less than 2 μL. Moreover, microfluidic and acoustic heating performances of AlN/Si SAWs were further studied and compared with those conventional ZnO/Si SAWs with the same electrode configurations

Developing an annual global Sub-National scale economic data from 1992 to 2021 using nighttime lights and deep learning

The Gross Domestic Product (GDP) per capita is one of the most widely used socioeconomic indicators, serving as an integral component for climate change impact analysis. However, a national scale assessment may induce considerable bias because it conceals any internal variations within a country. The lack of a long-term sub-national scale GDP data is a substantive hinderance. Leveraging the close relationship between nighttime lights and GDP, we address this gap by developing a novel methodological framework in two steps. First, under the modeling philosophy of spatial statistics, we developed a novel approach based on deep and machine learning techniques to establish a complex mapping between two inconsistent nighttime lights (NTL) datasets: the Defense Meteorological Satellite Program’s Operational Linescan System (DMSP) and the National Polar-Orbiting Partnership’s Visible Infrared Imaging Radiometer Suite (VIIRS). The models achieve accuracies ranging from 0.945 to 0.980 (correlation coefficients). By taking the estimations ensemble of the two techniques, the time series of DMSP data was extended to 2021. Next, a novel modeling strategy based on multi-layer perceptron was developed to derive the non-linear relationship between NTL and GDP per capita at sub-national scale to alleviate scale effects at this granularity, while explicitly capturing regional heterogeneity effect. The trained models achieve average accuracies of 0.967, 0.959, and 0.959 on the training, validation, and test sets, respectively. We evaluate the developed dataset at the global, national, and sub-national scales from various perspective, and the results offer solid evidence on the reliability of the estimated economic data. By linking to historical global climate change data, we quantify global economic losses attributed to extreme heat to demonstrate how the estimated GDP data can be useful in the climate change impact analysis

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

An Update Review on N-Type Layered Oxyselenide Thermoelectric Materials

Compared with traditional thermoelectric materials, layered oxyselenide thermoelectric materials consist of nontoxic and lower-cost elements and have better chemical and thermal stability. Recently, several studies on n-type layered oxyselenide thermoelectric materials, including BiCuSeO, Bi2O2Se and Bi6Cu2Se4O6, were reported, which stimulates us to comprehensively summarize these researches. In this short review, we begin with various attempts to realize an n-type BiCuSeO system. Then, we summarize several methods to optimize the thermoelectric performance of Bi2O2Se, including carrier engineering, band engineering, microstructure design, et al. Next, we introduce a new type of layered oxyselenide Bi6Cu2Se4O6, and n-type transport properties can be obtained through halogen doping. At last, we propose some possible research directions for n-type layered oxyselenide thermoelectric materials

PM2.5 Concentrations Variability in North China Explored with a Multi-Scale Spatial Random Effect Model

Compiling fine-resolution geospatial PM2.5 concentrations data is essential for precisely assessing the health risks of PM2.5 pollution exposure as well as for evaluating environmental policy effectiveness. In most previous studies, global and local spatial heterogeneity of PM2.5 is captured by the inclusion of multi-scale covariate effects, while the modelling of genuine scale-dependent variabilities pertaining to the spatial random process of PM2.5 has not yet been much studied. Consequently, this work proposed a multi-scale spatial random effect model (MSSREM), based a recently developed fixed-rank Kriging method, to capture both the scale-dependent variabilities and the spatial dependence effect simultaneously. Furthermore, a small-scale Monte Carlo simulation experiment was conducted to assess the performance of MSSREM against classic geospatial Kriging models. The key results indicated that when the multiple-scale property of local spatial variabilities were exhibited, the MSSREM had greater ability to recover local- or fine-scale variations hidden in a real spatial process. The methodology was applied to the PM2.5 concentrations modelling in North China, a region with the worst air quality in the country. The MSSREM provided high prediction accuracy, 0.917 R-squared, and 3.777 root mean square error (RMSE). In addition, the spatial correlations in PM2.5 concentrations were properly captured by the model as indicated by a statistically insignificant Moran&rsquo;s I statistic (a value of 0.136 with p-value &gt; 0.2). Overall, this study offers another spatial statistical model for investigating and predicting PM2.5 concentration, which would be beneficial for precise health risk assessment of PM2.5 pollution exposure

Inversion of time-frequency electromagnetic well seismic modeling to probe the inner structure of deep volcanic reservoir: A case study of LD area in Bohai Bay Basin

The seismic reflection of volcanic reservoir in deep basin is disorderly due to the influence of energy shielding, which makes the exploration of volcanic reservoir very difficult. Aimed at the complex inner structure of deep volcanic reservoir with multi-phase superposition, the optimal offset, time-frequency electromagnetic acquisition technology of the excitation period window, time-frequency electromagnetic well seismic joint modeling inversion and electrical variation rhythm coding volcanic period interpretation technology are studied, which effectively improved the depth resolution and the recognition ability of the method. The research and application effect in LD area of Bohai Bay Basin are obvious. The results show that the volcanic eruptions of the third member of Shahejie Formation in the Red Star tectonic belt show the characteristics of "two strong three weak" of "weak-strong-strong-weak-weak" from bottom to top. Two volcanic eruption mechanisms are developed, which jointly control the distribution of volcanic reservoir facies in five periods. In Taoyuan structural belt, the volcanic eruption intensity of each stage of the third member of the Shahejie Formation is significantly weakened, and only one volcanic eruption mechanism is developed. Except for the relatively large distribution range of volcanic reservoir facies in stage 3, the volcanic rocks in other stages are mainly confined to the crater, mainly in eruption facies, and their scale is significantly reduced. The follow-up drilling results confirmed that the distribution of volcanic reservoir revealed by time-frequency electromagnetic was correct, which provided strong support for the large oil and gas discovery in this area and provided a successful example and technical methods for the detection of similar complex targets