Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model.

We aimed to understand the genetic control of cardiac remodeling using an isoproterenol-induced heart failure model in mice, which allowed control of confounding factors in an experimental setting. We characterized the changes in cardiac structure and function in response to chronic isoproterenol infusion using echocardiography in a panel of 104 inbred mouse strains. We showed that cardiac structure and function, whether under normal or stress conditions, has a strong genetic component, with heritability estimates of left ventricular mass between 61% and 81%. Association analyses of cardiac remodeling traits, corrected for population structure, body size and heart rate, revealed 17 genome-wide significant loci, including several loci containing previously implicated genes. Cardiac tissue gene expression profiling, expression quantitative trait loci, expression-phenotype correlation, and coding sequence variation analyses were performed to prioritize candidate genes and to generate hypotheses for downstream mechanistic studies. Using this approach, we have validated a novel gene, Myh14, as a negative regulator of ISO-induced left ventricular mass hypertrophy in an in vivo mouse model and demonstrated the up-regulation of immediate early gene Myc, fetal gene Nppb, and fibrosis gene Lgals3 in ISO-treated Myh14 deficient hearts compared to controls

Structural insights into the gating of DNA passage by the topoisomerase II DNA-gate.

Type IIA topoisomerases (Top2s) manipulate the handedness of DNA crossovers by introducing a transient and protein-linked double-strand break in one DNA duplex, termed the DNA-gate, whose opening allows another DNA segment to be transported through to change the DNA topology. Despite the central importance of this gate-opening event to Top2 function, the DNA-gate in all reported structures of Top2-DNA complexes is in the closed state. Here we present the crystal structure of a human Top2 DNA-gate in an open conformation, which not only reveals structural characteristics of its DNA-conducting path, but also uncovers unexpected yet functionally significant conformational changes associated with gate-opening. This structure further implicates Top2's preference for a left-handed DNA braid and allows the construction of a model representing the initial entry of another DNA duplex into the DNA-gate. Steered molecular dynamics calculations suggests the Top2-catalyzed DNA passage may be achieved by a rocker-switch-type movement of the DNA-gate

Biodiversity survey and estimation for line-transect sampling

Conducting biodiversity surveys using a fully randomised design can be difficult due to budgetary constraints (e.g., the cost of labour), site accessibility, and other constraints. To this end, ecologists usually select representative line transects or quadrats from a studied area to collect individuals of a given species and use this information to estimate the levels of biodiversity over an entire region. However, commonly used biodiversity estimators such as Rao’s quadratic diversity index (and especially the Gini–Simpson index) were developed based on the assumption of independent sampling of individuals. Therefore, their performance can be compromised or even misleading when applied to species abundance datasets that are collected from non-independent sampling. In this study, we utilise a Markov chain model and derive an associated parameter estimator to account for non-independence in sequential sampling. Empirical tests on two forest plots in tropical (Barro Colorado, Island of Panama) and subtropical (Heishiding Nature Reserve of Guangdong, China) regions and the continental-scale spatial distribution of Acacia species in Australia showed that our estimators performed reasonably well. The estimated parameter measuring the degree of non-independence of subsequent sampling showed that a non-independent effect is very likely to occur when using line transects to sample organisms in subtropical regions at both local and regional spatial scales. In summary, based on a first-order Markov sampling model and using Rao’s quadratic diversity index as an example, our study provides an improvement in diversity estimation while simultaneously accounting for the non-independence of sampling in field biodiversity surveys. Our study presents one possible solution for addressing the non-independent sampling of individuals in biodiversity surveys

Introduction of a strong temperature-sensitive phenotype into enterovirus 71 by altering an amino acid of virus 3D polymerase

AbstractIn 1998, an enterovirus 71 (EV71) epidemic in Taiwan resulted in 78 deaths; however, the molecular basis of EV71 pathogenicity remains poorly understood. Comparison of the deduced amino acid sequences in 3D polymerases of EV71clinical isolates showed the T251V or T251I substitution from 1986 and 1998 outbreaks. An EV71 replicon system showed that introducing an I251T mutation did not affect luciferase activities at 35 °C when compared with wild type; however, lower luciferase activities were observed when they were incubated at 39.5 °C. In addition, the I251T mutation in the EV71 infectious clone not only reduced viral replication at 39.5 °C in vitro but also decreased the virulence of the mouse adaptive strain MP4 in neonatal mice in an i.p. infection model. Therefore, these results suggested that the threonine at position 251 results in a temperature sensitivity phenotype of EV71 which may contribute to the attenuation of circulating strains

Quantifying Efficiency Loss of Perovskite Solar Cells by a Modified Detailed Balance Model

A modified detailed balance model is built to understand and quantify efficiency loss of perovskite solar cells. The modified model captures the light-absorption dependent short-circuit current, contact and transport-layer modified carrier transport, as well as recombination and photon-recycling influenced open-circuit voltage. Our theoretical and experimental results show that for experimentally optimized perovskite solar cells with the power conversion efficiency of 19%, optical loss of 25%, non-radiative recombination loss of 35%, and ohmic loss of 35% are the three dominant loss factors for approaching the 31% efficiency limit of perovskite solar cells. We also find that the optical loss will climb up to 40% for a thin-active-layer design. Moreover, a misconfigured transport layer will introduce above 15% of energy loss. Finally, the perovskite-interface induced surface recombination, ohmic loss, and current leakage should be further reduced to upgrade device efficiency and eliminate hysteresis effect. The work contributes to fundamental understanding of device physics of perovskite solar cells. The developed model offers a systematic design and analysis tool to photovoltaic science and technology.Comment: 21 pages, 9 figures, 3 table

Deep Complex U-Net with Conformer for Audio-Visual Speech Enhancement

Recent studies have increasingly acknowledged the advantages of incorporating visual data into speech enhancement (SE) systems. In this paper, we introduce a novel audio-visual SE approach, termed DCUC-Net (deep complex U-Net with conformer network). The proposed DCUC-Net leverages complex domain features and a stack of conformer blocks. The encoder and decoder of DCUC-Net are designed using a complex U-Net-based framework. The audio and visual signals are processed using a complex encoder and a ResNet-18 model, respectively. These processed signals are then fused using the conformer blocks and transformed into enhanced speech waveforms via a complex decoder. The conformer blocks consist of a combination of self-attention mechanisms and convolutional operations, enabling DCUC-Net to effectively capture both global and local audio-visual dependencies. Our experimental results demonstrate the effectiveness of DCUC-Net, as it outperforms the baseline model from the COG-MHEAR AVSE Challenge 2023 by a notable margin of 0.14 in terms of PESQ. Additionally, the proposed DCUC-Net performs comparably to a state-of-the-art model and outperforms all other compared models on the Taiwan Mandarin speech with video (TMSV) dataset

Enhanced third harmonic generation by organic materials on high-Q plasmonic photonic crystals

The enhanced optical nonlinearity enabled by localized plasmonic fields has been well studied for all-optical switching processing (AOSP) devices for future optical communication systems. In this work, plasmonic photonic crystals with a nonlinear polycarbonate/polymethine blend cladding layer are designed to enhance the third harmonic generation (THG) at the telecom wavelengths (~1550 nm). Due to the presence of he two-dimensional (2-D) gold nano-patch arrays with improved Q-factor and high local fields, more than 20 × of enhanced THG signals in the hybrid organic-plasmonic nanostructure are experimentally observed. The enhanced THG in the hybrid organic-plasmonic materials suggested that such extraordinary nonlinear effects can be used for AOSP devices and wavelength conversion.This is the publisher’s final pdf. The published article is copyrighted by the Optical Society of America and can be found at: http://www.opticsinfobase.org/oe/home.cfm

A cytoplasmic RNA virus generates functional viral small RNAs and regulates viral IRES activity in mammalian cells

The roles of virus-derived small RNAs (vsRNAs) have been studied in plants and insects. However, the generation and function of small RNAs from cytoplasmic RNA viruses in mammalian cells remain unexplored. This study describes four vsRNAs that were detected in enterovirus 71-infected cells using next-generation sequencing and northern blots. Viral infection produced substantial levels (\u3e105 copy numbers per cell) of vsRNA1, one of the four vsRNAs. We also demonstrated that Dicer is involved in vsRNA1 generation in infected cells. vsRNA1 overexpression inhibited viral translation and internal ribosomal entry site (IRES) activity in infected cells. Conversely, blocking vsRNA1 enhanced viral yield and viral protein synthesis. We also present evidence that vsRNA1 targets stem-loop II of the viral 5′ untranslated region and inhibits the activity of the IRES through this sequence-specific targeting. Our study demonstrates the ability of a cytoplasmic RNA virus to generate functional vsRNA in mammalian cells. In addition, we also demonstrate a potential novel mechanism for a positive-stranded RNA virus to regulate viral translation: generating a vsRNA that targets the IRES