bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic response of multi-scale geophysical systems: waves and practical applications
Authors: Yakovleva Alexandra A. , Movchan Igor B. , Shaygallyamova Zilya I. 
Published: October 2022

In this review paper, we discuss the nature of an apparent link between heterogeneities associated with geological anomalies hidden from direct observation, detected when they are analysed remotely from various distances—including borehole conditions as well as aero imaging. Here, the main emphasis is placed on geological and geophysical features represented by spatially distributed signals measured along drilled well or along predefined spatial routes. In the common practice of indirect measurements of parameters of seismically active regions, there exist certain observations on correlations in the vicinity of structural and geological anomalies, repeated patterns in the representation of correlation functions and corresponding classification in multidimensional statistical methods. Underlying natural physical processes, which determine the structure of the primary anomalous environment, are of interest. Physical analogies, based on the mathematical modelling and generalization of empirical data, may suggest that such a process may be linked to wave phenomena on a geological scale. Applications include analysis of anomalies associated with non-potential fields, mapping of geodynamic zones and seismic microzoning; reconstruction of the geostructural vertical section of the mountainous regions.
This article is part of the theme issue 'Wave generation and transmission in multi-scale complex media and structured metamaterials (part 2)'.
Tuning the decay of sound in a viscous metamaterial
Authors: Ibarias M. , Doporto J. , Krokhin A. A. , Arriaga J. 
Published: October 2022

Using analytical results for viscous dissipation in phononic crystals, we calculate the decay coefficient of a sound wave propagating at low frequencies through a two-dimensional phononic crystal with a viscous fluid background. It is demonstrated that the effective acoustic viscosity of the phononic crystal may exceed by two to four orders of magnitude the natural hydrodynamic viscosity of the background fluid. Moreover, the decay coefficient exhibits dependence on the direction of propagation; that is, a homogenized phononic crystal behaves like an anisotropic viscous fluid. Strong dependence on the filling fraction of solid scatterers offers the possibility of tuning the dissipative decay length of sound, which is an important characteristic of any acoustic device.
This article is part of the theme issue ‘Wave generation and transmission in multi-scale complex media and structured metamaterials (part 2)’.
Different Associations of Anthropometric Indices with Diabetic Retinopathy and Diabetic Kidney Disease in Chinese Patients with Type 2 Diabetes Mellitus
Authors: Wang Yujie , Pang Xin , Gu Chufeng , Li Chenxin , Li Bo , Zhou Chuandi , Chen Haibing , Zheng Zhi 
Published: October 2022

AbstractAimsTo investigate the associations of anthropometric indices, including body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), waist circumference (WC) and hip circumference (HC), with diabetic retinopathy (DR) and diabetic kidney disease (DKD) in Chinese patients with type 2 diabetes mellitus (T2DM).Materials and methodsThis cross-sectional study evaluated 5226 participants with T2DM at Shanghai General Hospital between 2005 and 2016. Logistic regression models and restricted cubic spline analysis were used to assess the associations of anthropometric indices with DR and DKD.ResultsA BMI of around 25 kg/m2 was related to a low risk of DR (OR based on the third fifth: 0.752, 95%CI: 0.615-0.920). Besides, HC had an inverse association with DR in men independently of BMI (OR based on the highest fifth: 0.495, 95%CI: 0.350-0.697). In the restricted cubic spline models, BMI, WHtR, WC, and HC showed J-shaped associations with DKD, while WHR showed an S-shaped association with DKD. Compared to the lowest fifth, the odds ratios (OR) based on the highest fifth of BMI, WHR, WHtR, WC and HC for DKD were 1.927 (1.572-2.366), 1.566 (1.277-1.923), 1.91 (1.554-2.351), 1.91 (1.554-2.351) and 1.585 (1.300-1.937) respectively in multivariable models.ConclusionsA median BMI and a large hip might be related to a low risk of DR, while lower levels of all the anthropometric indices were associated with a lower risk of DKD. Our findings suggested maintain a median BMI, a low WHR, a low WHtR and a large hip for prevention of DR and DKD.
Prioritization of new candidate genes for rare genetic diseases by a disease-aware evaluation of heterogeneous molecular networks
Authors: de la Fuente Lorena , Del Pozo-Valero Marta , Perea-Romero Irene , Blanco-Kelly Fiona , Fernández-Caballero Lidia , Cortón Marta , Ayuso Carmen , Mínguez Pablo 
Published: October 2022

ABSTRACTScreening for pathogenic variants in the diagnosis of rare genetic diseases can now be performed on all genes thanks to the application of whole exome and genome sequencing (WES, WGS). Yet the repertoire of gene-disease associations is not complete. Several computer-based algorithms and databases integrate distinct gene-gene functional networks to accelerate the discovery of gene-disease associations. We hypothesize that the ability of every type of information to extract relevant insights is disease-dependent. We compiled 33 functional networks classified into 13 knowledge categories (KCs) and observed large variability in their ability to recover genes associated with 91 genetic diseases, as measured using efficiency and exclusivity. We developed GLOWgenes, a network-based algorithm that applies random walk with restart to evaluate KCs ability to recover genes from a given list associated with a phenotype, and modulates the prediction of new candidates accordingly. Comparison with other integration strategies and tools shows that our disease-aware approach can boost the discovery of new gene-disease associations, especially for the less obvious ones. KC contribution also varies if obtained using recently discovered genes. Applied to 15 unsolved WES, GLOWgenes proposed three new genes to be involved in the phenotypes of patients with syndromic inherited retinal dystrophies.
Applying GAN-based data augmentation to improve transcriptome-based prognostication in breast cancer
Authors: Guttà Cristiano , Morhard Christoph , Rehm Markus 
Published: October 2022

AbstractEstablished prognostic tests based on limited numbers of transcripts can identify high-risk breast cancer patients yet are approved only for individuals presenting with specific clinical features or disease characteristics. Deep learning algorithms could hold potential for stratifying patient cohorts based on full transcriptome data, yet the development of robust classifiers is hampered by the number of variables in omics datasets typically far exceeding the number of patients. To overcome this hurdle, we propose a classifier based on a data augmentation pipeline consisting of a Wasserstein generative adversarial network (GAN) with gradient penalty and an embedded auxiliary classifier to obtain a trained GAN discriminator (T-GAN-D). Applied to 1244 patients of the METABRIC breast cancer cohort, this classifier outperformed established breast cancer biomarkers in separating low- from high-risk patients (disease specific death, progression or relapse within 10 years from initial diagnosis). Importantly, the T-GAN-D also performed across independent, merged transcriptome datasets (METABRIC and TCGA-BRCA cohorts), and merging data improved overall patient stratification. In conclusion, GAN-based data augmentation therefore allowed generating a robust classifier capable of stratifying low- vs high-risk patients based on full transcriptome data and across independent and heterogeneous breast cancer cohorts.
THE IMPACT OF THE COVID-19 LOCKDOWN ON BIRTH WEIGHT AMONG SINGLETON TERM BIRTHS IN DENMARK
Authors: de Knegt Victoria E. , Hedley Paula L. , Hedermann Gitte , Wilstrup Casper , Bækvad-Hansen Marie , Thagaard Ida N. , Hjalgrim Henrik , Kanters Jørgen , Melbye Mads , Hougaard David M. , Hviid Anders , Krebs Lone , Breindahl Morten , Lausten-Thomsen Ulrik , Christiansen Michael 
Published: October 2022

AbstractIn Denmark, a nationwide COVID-19 lockdown was implemented on March 12, 2020 and eased on April 14, 2020. The COVID-19 lockdown featured reduced prevalence of extremely preterm or extremely low birth weight births. Here we explore the impact of this COVID-19 lockdown on term birth weights in Denmark.We conducted a nationwide register-based cohort study on 27,870 live singleton infants, born at term (weeks 37-41), between March 12 and April 14, 2015-2020, using data from the Danish Neonatal Screening Biobank. Primary outcomes, corrected for confounders, were birth weight, small-for-gestational-age (SGA), and large-for-gestational-age (LGA), comparing the COVID-19 lockdown to the previous five years. Data were analysed using linear regression to assess associations with birth weight. Multinomial logistic regression was used to assess associations with size-for-gestational-age (xGA) categories.Adjusted mean birth weight was significantly increased by 16.9 g (95% CI = 4.1 – 31.3) during the lockdown period. A dip in mean birth weight was found in gestational weeks 37 and 38 balanced by an increase in weeks 40 and 41. The 2020 lockdown period was associated with an increased LGA prevalence (aOR 1.13, 95% CI = 1.05 - 1.21). No significant changes in proportions of xGA groups were found between 2015 and 2019.ConclusionThe nationwide COVID-19 lockdown resulted in a small but significant increase in birth weight and proportion of LGA infants, driven by an increase in birth weight in gestational weeks 40 and 41.What is knownThe COVID-19 lockdown periods have had profound, albeit variable, effects on pregnant women in various countries.Extremely preterm and stillbirth rates were reduced during COVID-19 lockdown/mitigation periods in DenmarkWhat is newDuring COVID-19 lockdown a moderate, but statistically significant, increase in birth weight was seen.The proportion of large-for-gestational age pregnancies was statistically significantly elevated in the lockdown period.
Predation, community asynchrony, and metacommunity stability in cyanobacterial mats
Authors: Cissell Ethan C. , McCoy Sophie J. 
Published: October 2022

ABSTRACTThe dynamism of ecological interactions in rapidly changing ecosystems can be understood only by linking community context to population dynamics. Holistic characterization of such mechanisms requires integrating patterns of variability across scales. Here, we integrated observational, experimental, and theoretical approaches to unify local and regional ecological processes driving the dynamics of benthic cyanobacterial mats on coral reefs off the island of Bonaire, Caribbean Netherlands. Community and metacommunity dynamics of mats were tracked for 49 days alongside quantification of macropredation pressure from fishes. We tested the hypothesis that enhanced predation would result in decreased mat persistencein situ. Finally, we constructed a cellular automaton model to predict patterns in mat metacommunity dynamics across different scenarios of top-down and bottom-up control and dispersal. Cyanobacterial mat metacommunities were temporally stable across the study, stabilized by asynchrony in the dynamics of communities. Diverse reef fishes foraged on matsin situand experimental increases in predation pressure decreased the instantaneous mortality rate of mat communities over mat communities experiencing natural levels of predation pressure. Theoretical simulations suggested that dispersal conveys a rescuing effect on mat metacommunity abundance under scenarios of strong trophic control.
Inhibition of the SARS-CoV-2 helicase at single-nucleotide resolution
Authors: Marx Sinduja K. , Mickolajczyk Keith J. , Craig Jonathan M. , Thomas Christopher A. , Pfeffer Akira M. , Abell Sarah J. , Carrasco Jessica D. , Franzi Michaela C. , Huang Jesse R. , Kim Hwanhee C. , Brinkerhoff Henry D. , Kapoor Tarun M. , Gundlach Jens H. , Laszlo Andrew H. 
Published: October 2022

AbstractThe genome of SARS-CoV-2 encodes for a helicase called nsp13 that is essential for viral replication and highly conserved across related viruses, making it an attractive antiviral target. Here we use nanopore tweezers, a high-resolution single-molecule technique, to gain detailed insight into how nsp13 turns ATP-hydrolysis into directed motion along nucleic acid strands. We measured nsp13 both as it translocates along single-stranded DNA or unwinds short DNA duplexes. Our data confirm that nsp13 uses the inchworm mechanism to move along the DNA in single-nucleotide steps, translocating at ~1000 nt/s or unwinding at ~100 bp/s. Nanopore tweezers’ high spatio-temporal resolution enables observation of the fundamental physical steps taken by nsp13 even as it translocates at speeds in excess of 1000 nucleotides per second enabling detailed kinetic analysis of nsp13 motion. As a proof-of-principle for inhibition studies, we observed nsp13’s motion in the presence of the ATPase inhibitor ATPγS. Our data reveals that ATPγS interferes with nsp13’s action by affecting several different kinetic processes. The dominant mechanism of inhibition differs depending on the application of assisting force. These advances demonstrate that nanopore tweezers are a powerful method for studying viral helicase mechanism and inhibition.
Optimising ddRAD sequencing for population genomic studies with ddgRADer
Authors: Lajmi Aparna , Glinka Felix , Privman Eyal 
Published: October 2022

AbstractDouble-digest Restriction-site Associated DNA sequencing (ddRADseq) is widely used to generate genomic data for non-model organisms in evolutionary and ecological studies. Along with affordable paired-end sequencing, this method makes population genomic analyses more accessible. However, multiple factors should be considered when designing a ddRADseq experiment, which can be challenging for new users. The generated data often suffer from substantial read overlaps and adaptor contamination, severely reducing sequencing efficiency and at times affecting data quality. Here, we analyse diverse datasets from the literature and carry out controlled experiments to understand the effects of enzyme choice and size selection on sequencing efficiency. The empirical data reveal that size selection is imprecise and has limited efficacy. In certain scenarios, a substantial proportion of short fragments pass below the lower size-selection cut-off resulting in low sequencing efficiency. However, enzyme choice can considerably mitigate inadvertent inclusion of these shorter fragments. A simple model based on these experiments is implemented to predict the number of genomic fragments generated after digestion and size selection, number of SNPs genotyped, number of samples that can be multiplexed, and the expected sequencing efficiency. We developed ddgRADer -http://ddgrader.haifa.ac.il/- a user-friendly webtool that aids ddRADseq experimental design while optimising sequencing efficiency. This tool can also be used for single enzyme protocols such as Genotyping-by-Sequencing (GBS). Given user-defined study goals, ddgRADer recommends enzyme pairs and allows users to compare and choose enzymes and size-selection criteria. ddgRADer improves the accessibility and ease of designing ddRADseq experiments and increases the probability of success of the first population genomic study conducted in labs with no prior experience in genomics.
LSD1 acts as an epigenetic barrier against glucocorticoid-induced atrophy and exercise-induced hypertrophy in skeletal muscle
Authors: Araki Hirotaka , Hino Shinjiro , Anan Kotaro , Kuribayashi Kanji , Etoh Kan , Seko Daiki , Takase Ryuta , Kohrogi Kensaku , Hino Yuko , Ono Yusuke , Araki Eiichi , Nakao Mitsuyoshi 
Published: October 2022

AbstractSkeletal muscle exhibits remarkable plasticity in response to environmental cues, with stress-dependent effects on the fast-twitch and slow-twitch fibers. Although stress-induced gene expression underlies environmental adaptation, it is unclear how transcriptional and epigenetic factors regulate fiber type-specific responses in the muscle. Here, we show that flavin-dependent lysine-specific demethylase 1 (LSD1) differentially controls responses to glucocorticoid and exercise in postnatal skeletal muscle. Using skeletal muscle-specific LSD1 knockout mice andin vitroapproaches, we found that LSD1 loss exacerbated glucocorticoid-induced atrophy in the fast fiber-dominant muscles, with reduced nuclear retention of Foxk1, an anti-autophagic transcription factor. Furthermore, LSD1 depletion enhanced endurance exercise-induced hypertrophy in the slow fiber-dominant muscles, by induced expression of ERRγ, a transcription factor that promotes oxidative metabolism genes. Thus, LSD1 serves as an “epigenetic barrier” that optimizes fiber type-specific responses and muscle mass under the stress conditions. Our results uncover that LSD1 modulators provide emerging therapeutic and preventive strategies against stress-induced myopathies such as sarcopenia, cachexia, and disuse atrophy.Graphical abstract. LSD1 serves as an “epigenetic barrier” that defines stress sensitivities in the skeletal muscleLSD1 attenuates glucocorticoid (GC)-induced atrophy in the fast fiber-dominant muscles, in collaboration with Foxk1, an anti-autophagic transcription factor. On the other hand, LSD1 attenuates endurance exercise-induced hypertrophy in the slow fiber-dominant muscles, by inhibiting ERRγ, a transcription factor that promotes oxidative metabolism genes. The loss of LSD1 remarkably sensitized the muscles to GC and endurance exercise.
The START domain potentiates HD-ZIPIII transcriptional activity
Authors: Husbands Aman Y. , Feller Antje , Aggarwal Vasudha , Dresden Courtney E. , Holub Ashton S. , Ha Taekjip , Timmermans Marja C.P. 
Published: October 2022

AbstractHD-ZIPIII transcription factors (TFs) were repeatedly deployed over 725 million years of evolution to regulate central developmental innovations. The START domain of this pivotal class of developmental regulators was recognized over twenty years ago, but its putative ligands and functional contributions remain unknown. Here, we demonstrate that the START domain promotes HD-ZIPIII TF homodimerization and increases transcriptional potency. Effects on transcriptional output can be ported onto heterologous TFs, consistent with principles of evolution via domain capture. We also show the START domain binds several species of phospholipids, and that mutations in conserved residues predicted to affect either ligand binding, or its downstream readout, abolish HD-ZIPIII DNA-binding competence. Our data present a model in which the START domain potentiates transcriptional activity and uses ligand-induced conformational change to render HD-ZIPIII dimers competent to bind DNA. These findings resolve a long-standing mystery in plant development and highlight the flexible and diverse regulatory potential coded within this widely distributed evolutionary module.
SiRNA Molecules as Potential RNAi Therapeutics to Silence RdRP Region and N-Gene of SARS-CoV-2: An In Silico Approach
Authors: Hasan Mahedi , Tasnim Atiya Tahira , Ashik Arafat Islam , Chowdhury Md Belal , Nishat Zakia Sultana , Fariha Khandaker Atkia , Hossain Tanvir , Ahmed Shamim 
Published: October 2022

AbstractCOVID-19 pandemic keeps pressing onward and effective treatment option against it is still far-off. Since the onslaught in 2020, 13 different variants of SARS-CoV-2 have been surfaced including 05 different variants of concern. Success in faster pandemic handling in the future largely depends on reinforcing therapeutics along with vaccines. As a part of RNAi therapeutics, here we developed a computational approach for predicting siRNAs, which are presumed to be intrinsically active against two crucial mRNAs of SARS-CoV-2, the RNA-dependent RNA polymerase (RdRp), and the nucleocapsid phosphoprotein gene (N gene). Sequence conservancy among the alpha, beta, gamma, and delta variants of SARS-CoV-2 was integrated in the analyses that warrants the potential of these siRNAs against multiple variants. We preliminary found 13 RdRP-targeting and 7 N gene-targeting siRNAs using the siDirect V.2.0. These siRNAs were subsequently filtered through different parameters at optimum condition including macromolecular docking studies. As a result, we selected 4 siRNAs against the RdRP and 3 siRNAs against the N-gene as RNAi candidates. Development of these potential siRNA therapeutics can significantly synergize COVID-19 mitigation by lessening the efforts, furthermore, can lay a rudimentary base for the in silico design of RNAi therapeutics for future emergencies.
Speech and music recruit frequency-specific distributed and overlapping cortical networks
Authors: Rietmolen Noémie te , Mercier Manuel , Trébuchon Agnès , Morillon Benjamin , Schön Daniele 
Published: October 2022

AbstractTo what extent does speech and music processing rely on domain-specific and domain-general neural networks? Using whole-brain intracranial EEG recordings in 18 epilepsy patients listening to natural, continuous speech or music, we investigated the presence of frequency-specific and network-level brain activity. We combined it with a statistical approach in which a clear operational distinction is made betweenshared,preferred,and domain-selectiveneural responses. We show that the majority of focal and network-level neural activity is shared between speech and music processing. Our data also reveal an absence of anatomical regional selectivity. Instead, domain-selective neural responses are restricted to distributed and frequency-specific coherent oscillations, typical of spectral fingerprints. Our work highlights the importance of considering natural stimuli and brain dynamics in their full complexity to map cognitive and brain functions.
The RNA m6A reader YTHDF1 promotes hematopoietic malignancy by maintaining oncogenic translation
Authors: Hong Yun-Guang , Yang Zhigang , Chen Yan , Liu Tian , Zheng Yuyuan , Wu Guo-Cai , Chen Yinhui , Xia Juan , Wen Ruiting , Liu Wenxin , Zhao Yi , Chen Jin , Gao Xiangwei , Chen Zhanghui 
Published: October 2022

ABSTRACTN6-methyladenosine (m6A), the most abundant modification in mRNAs, has been defined as a crucial modulator in the progression of acute myeloid leukemia (AML), while the detailed mechanism remains elusive. Here we report that YTHDF1, an m6A reader protein, is overexpressed in human AML samples with enrichment in leukemia stem cells (LSCs). Whereas YTHDF1 is dispensable for normal hematopoiesis in mice, depletion of YTHDF1 attenuates self-renewal and proliferation of patient-derived LSCs, and impedes leukemia establishment in immunodeficient mice. Mechanistically, YTHDF1 promotes the translation of diverse m6A-modified oncogene mRNAs particularlycyclin E2. We applied a structure-based virtual screening of FDA-approved drugs and identified tegaserod as a potential YTHDF1 inhibitor. Tegaserod blocks the direct binding of YTHDF1 with m6A-modified mRNAs and inhibits YTHDF1-regulated mRNA translation. Moreover, tegaserod inhibits leukemogenesisin vitroand in mice, phenocopying the loss of YTHDF1. Together, our study defines YTHDF1 as an integral regulator of AML progression at the translational level and identifies tegaserod as a potential therapeutic agent for AML by targeting YTHDF1.Statement of SignificanceThe RNA m6A reader YTHDF1 is an oncoprotein in AML.YTHDF1 promotes the translation of m6A-modified oncogene mRNAs.Tegaserod, an FDA-approved drug for irritable bowel syndrome, inhibits YTHDF1-regulated mRNA translation and leukemogenesis.Graphical Abstract