Functional redundancy of EGF-CFC genes in epiblast and extraembryonic patterning during early mouse embryogenesis

AbstractDuring early mouse embryogenesis, multiple patterning and differentiation events require the activity of Nodal, a ligand of the transforming growth factor-beta (TGFβ) family. Although Nodal signaling is known to require activity of EGF-CFC co-receptors in many contexts, it has been unclear whether all Nodal signaling in the early mouse embryo is EGF-CFC dependent. We have investigated the double null mutant phenotypes for the EGF-CFC genes Cripto and Cryptic, which encode co-receptors for Nodal, and have found that they have partially redundant functions in early mouse development. Expression of Cripto and Cryptic is non-overlapping prior to gastrulation, since Cripto is expressed solely in the epiblast whereas Cryptic is expressed in the primitive endoderm of the late blastocyst and the visceral endoderm after implantation. Despite these non-overlapping expression patterns, Cripto; Cryptic double mutants display severe defects in epiblast, extraembryonic ectoderm, and anterior visceral endoderm (AVE), resulting in phenotypes that are highly similar to those of Nodal null mutants. Our results indicate that both Cripto and Cryptic function non-cell-autonomously during normal development, and that most if not all Nodal activity in early mouse embryogenesis is EGF-CFC-dependent

Parametric study of unsteady-flow-induced volute casing vibro-acoustics in a centrifugal fan

A numerical parametric analysis of a vibro-acoustic coupling method that considered the influence of vibro-acoustic coupling was carried out to investigate the casing vibrations and feathers of vibrational noise induced by unsteady flow of the centrifugal fan at the best-efficiency point (BEP). There are three important aspects of this method. First, an unsteady flow-field with a whole impeller-volute configuration was solved based on three-dimensional incompressible Navier-Stokes equations and a standard k-ε turbulence mode to obtain the source of the vibro-acoustics. Second, a one-way-flow structural acoustic coupling method was implemented to study the volute vibrations and behaviors of vibrational noise by adoption. The generation mechanism of vibrational noise of the volute casing was revealed. Third, the parametric analysis method was used to explore the parametric relationship between the panel thicknesses (such as front-panel thickness [FT], side-panel thickness [ST], and back-panel thickness [BT]) and the outlet acoustical power of the volute casing surface. The parametric analysis provides a reasonable range of values of three panel thicknesses that result in minimal vibrational sound radiation

From intention to action:Enabling sustainable agriculture in emerging economies through decentralized regulations for manure management

This study contributes to the debate about effective regulatory strategies for environmental regulation in achieving sustainable agriculture, particularly in understudied emerging economies. We leverage the case of swine manure recovery in China to illuminate this crucial but under‐researched context. Building on the theory of planned behavior, which posits a gap between intention and behavior, we investigate how these regulations and their combinations influence swine farmers' intentions and behaviors toward resource recovery. Findings reveal command‐and‐control regulations most effectively stimulate initial intentions, while incentive‐based regulations work best in bridging the gap between intention and action. Information‐based approaches further strengthen this conversion, particularly when combined with incentives. Bridging the disciplines of regulation and behavioral science, this study advances theoretical understanding of the intention‐behavior gap in environmental policy. It informs effective regulation design that promote sustainable agricultural practices in developing countries, ultimately contributing to achieving the Sustainable Development Goals

High-fat feeding reprograms maternal energy metabolism and induces long-term postpartum obesity in mice.

BackgroundExcessive gestational weight gain (EGWG) closely associates with postpartum obesity. However, the causal role of EGWG in postpartum obesity has not been experimentally verified. The objective of this study was to determine whether and how EGWG causes long-term postpartum obesity.MethodsC57BL/6 mice were fed with high-fat diet during gestation (HFFDG) or control chow, then their body composition and energy metabolism were monitored after delivery.ResultsWe found that HFFDG significantly increased gestational weight gain. After delivery, adiposity of HFFDG-treated mice (Preg-HF) quickly recovered to the levels of controls. However, 3 months after parturition, Preg-HF mice started to gain significantly more body fat even with regular chow. The increase of body fat of Preg-HF mice was progressive with aging and by 9 months after delivery had increased 2-fold above the levels of controls. The expansion of white adipose tissue (WAT) of Preg-HF mice was manifested by hyperplasia in visceral fat and hypertrophy in subcutaneous fat. Preg-HF mice developed low energy expenditure and UCP1 expression in interscapular brown adipose tissue (iBAT) in later life. Although blood estrogen concentrations were similar between Preg-HF and control mice, a significant decrease in estrogen receptor α (ERα) expression and hypermethylation of the ERα promoter was detected in the fat of Preg-HF mice 9 months after delivery. Interestingly, hypermethylation of ERα promoter and low ERα expression were only detected in adipocyte progenitor cells in both iBAT and WAT of Preg-HF mice at the end of gestation.ConclusionsThese results demonstrate that HFFDG causes long-term postpartum obesity independent of early postpartum fat retention. This study also suggests that HFFDG adversely programs long-term postpartum energy metabolism by epigenetically reducing estrogen signaling in both BAT and WAT

Distinguishing Neural Speech Synthesis Models Through Fingerprints in Speech Waveforms

Recent strides in neural speech synthesis technologies, while enjoying widespread applications, have nonetheless introduced a series of challenges, spurring interest in the defence against the threat of misuse and abuse. Notably, source attribution of synthesized speech has value in forensics and intellectual property protection, but prior work in this area has certain limitations in scope. To address the gaps, we present our findings concerning the identification of the sources of synthesized speech in this paper. We investigate the existence of speech synthesis model fingerprints in the generated speech waveforms, with a focus on the acoustic model and the vocoder, and study the influence of each component on the fingerprint in the overall speech waveforms. Our research, conducted using the multi-speaker LibriTTS dataset, demonstrates two key insights: (1) vocoders and acoustic models impart distinct, model-specific fingerprints on the waveforms they generate, and (2) vocoder fingerprints are the more dominant of the two, and may mask the fingerprints from the acoustic model. These findings strongly suggest the existence of model-specific fingerprints for both the acoustic model and the vocoder, highlighting their potential utility in source identification applications.Comment: Submitted to ICASSP 202

Giα proteins exhibit functional differences in the activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells

Background In a classic model, Giα proteins including Gi1α, Gi2α and Gi3α are important for transducing signals from Giα protein-coupled receptors (GiαPCRs) to their downstream cascades in response to hormones and neurotransmitters. Our previous study has suggested that Gi1α, Gi2α and Gi3α are also important for the activation of the PI3K/Akt/mTORC1 pathway by epidermal growth factor (EGF) and its family members. However, a genetic role of these Giα proteins in the activation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) by EGF is largely unknown. Further, it is not clear whether these Giα proteins are also engaged in the activation of both the Akt/mTORC1 and ERK1/2 pathways by other growth factor family members. Additionally, a role of these Giα proteins in breast cancer remains to be elucidated. Results We found that Gi1/3 deficient MEFs with the low expression level of Gi2α showed defective ERK1/2 activation by EGFs, IGF-1 and insulin, and Akt and mTORC1 activation by EGFs and FGFs. Gi1/2/3 knockdown breast cancer cells exhibited a similar defect in the activations and a defect in in vitro growth and invasion. The Giα proteins associated with RTKs, Gab1, FRS2 and Shp2 in breast cancer cells and their ablation impaired Gab1’s interactions with Shp2 in response to EGF and IGF-1, or with FRS2 and Grb2 in response to bFGF. Conclusions Giα proteins differentially regulate the activation of Akt, mTORC1 and ERK1/2 by different families of growth factors. Giα proteins are important for breast cancer cell growth and invasion.Fil: Wang, Zhanwei. University of Hawaii Cancer Center. Honolulu; Estados UnidosFil: Dela Cruz, Rica. University of Hawaii Cancer Center. Honolulu; Estados UnidosFil: Ji, Fang. Shanghai Jiao Tong University . Sahnghai; ChinaFil: Guo, Sheng. University of Hawaii Cancer Center. Honolulu; Estados Unidos. Shanghai Jiaotong University. Shangha; Estados UnidosFil: Zhang, Jianhua. Shanghai Jiaotong University. Shangha; Estados Unidos. University of Hawaii Cancer Center. Honolulu; Estados UnidosFil: Wang, Ying. David Geffen School of Medicine at UCLA. Los Angeles; Estados UnidosFil: Feng, Gen-Sheng. University of California at San Diego; Estados UnidosFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institutes of Health; Estados UnidosFil: Jiang, Meisheng. David Geffen School of Medicine at UCLA. Los Angeles; Estados UnidosFil: Chu, Wen Ming. University of Hawaii Cancer Center. Honolulu; Estados Unido

Audio Deepfake Detection: A Survey

Audio deepfake detection is an emerging active topic. A growing number of literatures have aimed to study deepfake detection algorithms and achieved effective performance, the problem of which is far from being solved. Although there are some review literatures, there has been no comprehensive survey that provides researchers with a systematic overview of these developments with a unified evaluation. Accordingly, in this survey paper, we first highlight the key differences across various types of deepfake audio, then outline and analyse competitions, datasets, features, classifications, and evaluation of state-of-the-art approaches. For each aspect, the basic techniques, advanced developments and major challenges are discussed. In addition, we perform a unified comparison of representative features and classifiers on ASVspoof 2021, ADD 2023 and In-the-Wild datasets for audio deepfake detection, respectively. The survey shows that future research should address the lack of large scale datasets in the wild, poor generalization of existing detection methods to unknown fake attacks, as well as interpretability of detection results

Adaptive expression responses in the Pol-γ null strain of S. pombe depleted of mitochondrial genome

<p>Abstract</p> <p>Background</p> <p>DNA polymerase γ(Pol-γ) has been shown to be essential for maintenance of the mitochondrial genome (mtDNA) in the petite-positive budding yeast <it>Saccharomyces cerevisiae</it>. Budding yeast cells lacking mitochondria exhibit a slow-growing or petite-colony phenotype. Petite strains fail to grow on non-fermentable carbon sources. However, it is not clear whether the Pol-γ is required for mtDNA maintenance in the petite-negative fission yeast <it>Schizosaccharomyces pombe</it>.</p> <p>Results</p> <p>We show that disruption of the nuclear gene <it>pog1</it>⁺that encodes Pol-γ is sufficient to deplete mtDNA in <it>S. pombe</it>. Cells bearing <it>pog1Δ </it>allele require substantial growth periods to form petite colonies. Mitotracker assays indicate that <it>pog1Δ </it>cells are defective in mitochondrial function and EM analyses suggest that <it>pog1Δ </it>cells lack normal mitochondrial structures. Depletion of mtDNA in <it>pog1Δ </it>cells is evident from quantitative real-time PCR assays. Genome-wide expression profiles of <it>pog1Δ </it>and other mtDNA-less cells reveal that many genes involved in response to stimulus, energy derivation by oxidation of organic compounds, cellular carbohydrate metabolism, and energy reserve metabolism are induced. Conversely, many genes encoding proteins involved in amino acid metabolism and oxidative phosphorylation are repressed.</p> <p>Conclusion</p> <p>By showing that Pol-γ is essential for mtDNA maintenance and disruption of <it>pog1</it>⁺alters the genome-wide expression profiles, we demonstrated that cells lacking mtDNA exhibit adaptive nuclear gene expression responses in the petite-negative <it>S. pombe</it>.</p

The topological AC effect on noncommutative phase space

The Aharonov-Casher (AC) effect in non-commutative(NC) quantum mechanics is studied. Instead of using the star product method, we use a generalization of Bopp's shift method. After solving the Dirac equations both on noncommutative space and noncommutative phase space by the new method, we obtain the corrections to AC phase on NC space and NC phase space respectively.Comment: 8 pages, Latex fil

Interleukin-22 Inhibits Bleomycin-Induced Pulmonary Fibrosis

Pulmonary fibrosis is a progressive and fatal fibrotic disease of the lungs with unclear etiology. Recent insight has suggested that early injury/inflammation of alveolar epithelial cells could lead to dysregulation of tissue repair driven by multiple cytokines. Although dysregulation of interleukin- (IL-) 22 is involved in various pulmonary pathophysiological processes, the role of IL-22 in fibrotic lung diseases is still unclear and needs to be further addressed. Here we investigated the effect of IL-22 on alveolar epithelial cells in the bleomycin- (BLM-) induced pulmonary fibrosis. BLM-treated mice showed significantly decreased level of IL-22 in the lung. IL-22 produced γδT cells were also decreased significantly both in the tissues of lungs and spleens. Administration of recombinant human IL-22 to alveolar epithelial cell line A549 cells ameliorated epithelial to mesenchymal transition (EMT) and partially reversed the impaired cell viability induced by BLM. Furthermore, blockage of IL-22 deteriorated pulmonary fibrosis, with elevated EMT marker (α-smooth muscle actin (α-SMA)) and overactivated Smad2. Our results indicate that IL-22 may play a protective role in the development of BLM-induced pulmonary fibrosis and may suggest IL-22 as a novel immunotherapy tool in treating pulmonary fibrosis