bluuebunny/crossref_metadata_2025_split huggingface dataset:
INKILNis a novel long noncoding RNA promoting vascular smooth muscle inflammation via scaffolding MKL1 and USP10
Authors: Zhang Wei , Zhao Jinjing , Deng Lin , Ishimwe Nestor , Pauli Jessica , Wu Wen , Shan Shengshuai , Kempf Wolfgang , Ballantyne Margaret D , Kim David , Lyu Qing , Bennett Matthew , Rodor Julie , Turner Adam W. , Lu Yao Wei , Gao Ping , Choi Mihyun , Warthi Ganesh , Kim Ha Won , Barroso Margarida M , Bryant William B. , Miller Clint L. , Weintraub Neal L. , Maegdefessel Lars , Miano Joseph M. , Baker Andrew H , Long Xiaochun 
Published: January 2023

AbstractBackgroundActivation of vascular smooth muscle cells (VSMCs) inflammation is vital to initiate vascular disease. However, the role of human-specific long noncoding RNAs (lncRNAs) in VSMC inflammation is poorly understood.MethodsBulk RNA-seq in differentiated human VSMCs revealed a novel human-specific lncRNA calledINflammatory MKL1InteractingLongNoncoding RNA (INKILN).INKILNexpression was assessed in multiple in vitro and ex vivo models of VSMC phenotypic modulation and human atherosclerosis and abdominal aortic aneurysm (AAA) samples. The transcriptional regulation ofINKILNwas determined through luciferase reporter system and chromatin immunoprecipitation assay. Both loss- and gain-of-function approaches and multiple RNA-protein and protein-protein interaction assays were utilized to uncover the role ofINKILNin VSMC proinflammatory gene program and underlying mechanisms. Bacterial Artificial Chromosome (BAC) transgenic (Tg) mice were utilized to studyINKLINexpression and function in ligation injury-induced neointimal formation.ResultsINKILNexpression is downregulated in contractile VSMCs and induced by human atherosclerosis and abdominal aortic aneurysm.INKILNis transcriptionally activated by the p65 pathway, partially through a predicted NF-κB site within its proximal promoter.INKILNactivates the proinflammatory gene expression in cultured human VSMCs and ex vivo cultured vessels. Mechanistically,INKILNphysically interacts with and stabilizes MKL1, a key activator of VSMC inflammation through the p65/NF-κB pathway.INKILNdepletion blocks ILIβ-induced nuclear localization of both p65 and MKL1. Knockdown ofINKILNabolishes the physical interaction between p65 and MKL1, and the luciferase activity of an NF-κB reporter. Further,INKILNknockdown enhances MKL1 ubiquitination, likely through the reduced physical interaction with the deubiquitinating enzyme, USP10.INKILNis induced in injured carotid arteries and exacerbates ligation injury-induced neointimal formation in BAC Tg mice.ConclusionsThese findings elucidate an important pathway of VSMC inflammation involving anINKILN/MKL1/USP10 regulatory axis. Human BAC Tg mice offer a novel and physiologically relevant approach for investigating human-specific lncRNAs under vascular disease conditions.
Genomic evidence for rapid speciation and gene flow between sympatric carnivorousNepenthespitcher plants
Authors: Scharmann M , Metali F , Grafe T U , Widmer A 
Published: January 2023

AbstractSpeciation can result from both neutral and adaptive processes, but their relative importance and the factors exerting selective pressures are incompletely understood. In theory, interspecific gene flow could suffice to reverse speciation, or else erode neutral divergence and expose traits and underlying genes whose divergence is due to selection. Hence, introgression can shed light on selection during the speciation process. Here we study mixed assemblages of carnivorousNepenthespitcher plants, which frequently produce natural hybrids yet maintain distinct phenotypes. Using ddRAD-seq markers, we characterize divergence and introgression for eightNepenthesspecies that grow sympatrically in communities of three to seven species at four locations in Southeast Asia, totalling 22 populations. The sympatric species fell into two discrete classes of high and low divergence. Five lineages with high divergence displayed little recent introgression in tests of location-dependent allele sharing (ABBA-BABA) despite the presence of some natural hybrids. However, all five lineages appear to have introgressed in the more distant past, as revealed by coalescent models with Approximate Bayesian Computation. In the same locations occur three further sympatric species with low genetic divergence. These incipient species also showed some natural hybrids, but in addition both ABBA-BABA tests and ABC suggested very recent or ongoing introgression, raising the question how divergence is maintained in these hybrid zones. One trait possibly involved in maintenance of divergence against gene flow might be the carnivorous pitcher traps, whose morphology showed greater divergence than expected under neutral evolution (Pst–Fst) in the introgressing species pairN. hemsleyanaandN. rafflesianat.f..
Endothelial SMAD1/5 signaling couples angiogenesis to osteogenesis during long bone growth
Authors: Lang Annemarie , Benn Andreas , Wolter Angelique , Balcaen Tim , Collins Joseph , Kerckhofs Greet , Zwijsen An , Boerckel Joel D. 
Published: January 2023

AbstractSkeletal development depends on coordinated angiogenesis and osteogenesis. Bone morphogenetic proteins direct bone development by activating SMAD1/5 signaling in osteoblasts. However, the role of SMAD1/5 in skeletal endothelium is unknown. Here, we found that endothelial cell-conditional SMAD1/5 depletion in juvenile mice caused metaphyseal and diaphyseal hypervascularity, resulting in altered cancellous and cortical bone formation. SMAD1/5 depletion induced excessive sprouting, disrupting the columnar structure of the metaphyseal vessels and impaired anastomotic loop morphogenesis at the chondro-osseous junction. Endothelial SMAD1/5 depletion impaired growth plate resorption and, upon long term depletion, abrogated osteoprogenitor recruitment to the primary spongiosa. Finally, in the diaphysis, endothelial SMAD1/5 activity was necessary to maintain the sinusoidal phenotype, with SMAD1/5 depletion inducing formation of large vascular loops, featuring elevated endomucin expression, ectopic tip cell formation, and hyperpermeability. Together, endothelial SMAD1/5 activity sustains skeletal vascular morphogenesis and function and coordinates growth plate remodeling and osteoprogenitor recruitment dynamics during bone growth.
IraM Remodels the RssB Segmented Helical Linker to Stabilize σsagainst Degradation by ClpXP
Authors: Brugger C , Srirangam S , Deaconescu Alexandra M 
Published: January 2023

ABSTRACTUpon Mg2+starvation, a condition often associated with virulence, enterobacteria inhibit the ClpXP-dependent proteolysis of the master transcriptional regulator, σs, via IraM, a poorly understood anti-adaptor that prevents RssB-dependent loading of σsonto ClpXP. This inhibition results in σsaccumulation, and expression of stress resistance genes. Here we report on the structural analysis of RssB bound to IraM, which reveals that IraM induces two folding transitions within RssB, which are amplified via a segmental helical linker. This work highlights the remarkable structural plasticity of RssB and reveals how a stress-specific RssB antagonist modulates a core stress response pathway that could be leveraged to control biofilm formation, virulence, and the development of antibiotic resistance.
Development of Multiomicsin situPairwise Sequencing (MiP-Seq) for Single-cell Resolution Multidimensional Spatial Omics
Authors: Wu Xiaofeng , Xu Weize , Deng Lulu , Li Yue , Wang Zhongchao , Sun Leqiang , Gao Anran , Wang Haoqi , Yang Xiaodan , Wu Chengchao , Zou Yanyan , Yan Keji , Liu Zhixiang , Zhang Lingkai , Du Guohua , Yang Liyao , Lin Da , Wang Ping , Han Yunyun , Fu Zhenfang , Dai Jinxia , Cao Gang 
Published: January 2023

AbstractDelineating the spatial multiomics landscape will pave the way to understanding the molecular basis of physiology and pathology. However, current spatial omics technology development is still in its infancy. Here, we developed a high-throughput multiomicsin situpairwise sequencing (MiP-Seq) strategy to efficiently decipher multiplexed DNAs, RNAs, proteins, and small biomolecules at subcellular resolution. We delineated dynamic spatial gene profiles in the hypothalamus using MiP-Seq. Moreover, MiP-Seq was unitized to detect tumor gene mutations and allele-specific expression of parental genes and to differentiate sites with and without the m6A RNA modification at specific sites. MiP-Seq was combined within vivoCa2+imaging and Raman imaging to obtain a spatial multiomics atlas correlated to neuronal activity and cellular biochemical fingerprints. Importantly, we proposed a “signal dilution strategy” to resolve the crowded signals that challenge the applicability ofin situsequencing. Together, our method improves spatial multiomics and precision diagnostics and facilitates analyses of cell function in connection with gene profiles.
DPHL v2: An updated and comprehensive DIA pan-human assay library for quantifying more than 14,000 proteins
Authors: Xue Zhangzhi , Zhu Tiansheng , Zhang Fangfei , Zhang Cheng , Xiang Nan , Qian Liujia , Yi Xiao , Sun Yaoting , Liu Wei , Cai Xue , Wang Linyan , Dai Xizhe , Yue Liang , Li Lu , Pham Thang V. , Piersma Sander R. , Xiao Qi , Luo Meng , Lu Cong , Zhu Jiang , Zhao Yongfu , Wang Guangzhi , Xiao Junhong , Liu Tong , Liu Zhiyu , He Yi , Wu Qijun , Gong Tingting , Zhu Jianqin , Zheng Zhiguo , Ye Juan , Li Yan , Jimenez Connie R. , Jun A , Guo Tiannan 
Published: January 2023

SummaryA comprehensive pan-human spectral library is critical for biomarker discovery using mass spectrometry (MS)-based proteomics. DPHL v1, a previous pan-human library built from 1096 data-dependent acquisition (DDA) MS data of 16 human tissue types, allows quantifying 10,943 proteins. However, a major limitation of DPHL v1 is the lack of semi-tryptic peptides and protein isoforms, which are abundant in clinical specimens. Here, we generated DPHL v2 from 1608 DDA-MS data acquired using Orbitrap mass spectrometers. The data included 586 DDA-MS newly acquired from 17 tissue types, while 1022 files were derived from DPHL v1. DPHL v2 thus comprises data from 24 sample types, including several cancer types (lung, breast, kidney, and prostate cancer, among others). We generated four variants of DPHL v2 to include semi-tryptic peptides and protein isoforms. DPHL v2 was then applied to a publicly available colorectal cancer dataset with 286 DIA-MS files. The numbers of identified and significantly dysregulated proteins increased by at least 21.7% and 14.2%, respectively, compared with DPHL v1. Our findings show that the increased human proteome coverage of DPHL v2 provides larger pools of potential protein biomarkers.
Impact of urbanization on the taxonomic and functional diversity of spider assemblages in Guwahati City, Assam, India
Authors: Sharma Ankita , Deka Bitupan , Bishaya Puja , Kumar Raman , Sharma Narayan 
Published: January 2023

AbstractThe homogenous nature of the urban environment rapidly alters community dynamics of extant flora and fauna due to short-term spatial and temporal factors. However, such impacts of urbanization are mostly investigated in terms of taxonomic diversity, while its impact on functional diversity remains poorly understood. Whereas taxonomic information is limited to the identity of species, functional traits determine the relationship between species identity and ecosystem functioning. Studies investigating the role of urbanization in altering these ecological parameters have mostly focused on avian communities or plant species, while arthropods such as spiders which are integral components of urban households have largely been overlooked. This study aims to understand the impact of urbanization on both taxonomic diversity and functional diversity of spider assemblages across an urban–semi-urban–forest gradient in Guwahati, a rapidly growing city in northeast India. We surveyed spiders at 13 sites representing four habitat types (urban, urban parks, semi-urban, and forests) using belt transects, and also recorded functional traits relating to key life history processes. Spider species composition differed significantly between various habitats. The taxonomic diversity of spiders was highest in forests and lowest in urban parks. The turnover component was the major contributor to changing the β-diversity of spiders. Reduced diversity in urban regions was likely due to the dominance of a few synanthropic species. Generalised linear mixed-effects model analysis indicated that the habitat types significantly impacted spider abundance. Functional richness was maximum in forests (Fric= 23.43) and minimum in urban habitats (Fric= 12.98), while functional divergence was maximum in urban sites (Fdiv= 0.79). Our study demonstrates that urban land-use change can alter the structure and functioning of the spider community.
Mechanostat parameters estimated from time-lapsedin vivomicro-computed tomography data of mechanically driven bone adaptation are logarithmically dependent on loading frequency
Authors: Marques Francisco C. , Boaretti Daniele , Walle Matthias , Scheuren Ariane C. , Schulte Friederike A. , Müller Ralph 
Published: January 2023

AbstractMechanical loading is a key factor governing bone adaptation. Both preclinical and clinical studies have demonstrated its effects on bone tissue, which were also notably predicted in the mechanostat theory. Indeed, existing methods to quantify bone mechanoregulation have successfully associated the frequency of (re)modeling events with local mechanical signals, combining time-lapsedin vivomicro-computed tomography (micro-CT) imaging and micro-finite element (micro-FE) analysis. However, a correlation between the local surface velocity of (re)modeling events and mechanical signals has not been shown. As many degenerative bone diseases have also been linked to impaired bone (re)modeling, this relationship could provide an advantage in detecting the effects of such conditions and advance our understanding of the underlying mechanisms. Therefore, in this study, we introduce a novel method to estimate (re)modeling velocity curves from time-lapsedin vivomouse caudal vertebrae data under static and cyclic mechanical loading. These curves can be fitted with piecewise linear functions as proposed in the mechanostat theory. Accordingly, new (re)modeling parameters can be derived from such data, including formation saturation levels, resorption velocity modulus, and (re)modeling thresholds. Our results revealed that the norm of the gradient of strain energy density yielded the highest accuracy in quantifying mechanoregulation data using micro-FE analysis with homogeneous material properties, while effective strain was the best predictor for micro-FE analysis with heterogeneous material properties. Furthermore, (re)modeling velocity curves could be accurately described with piecewise linear and hyperbola functions (root mean square error below 0.2 µm/day for weekly analysis), and several (re)modeling parameters determined from these curves followed a logarithmic relationship with loading frequency. Crucially, (re)modeling velocity curves and derived parameters could detect differences in mechanically driven bone adaptation, which complemented previous results showing a logarithmic relationship between loading frequency and net change in bone volume fraction over four weeks. Together, we expect this data to support the calibration ofin silicomodels of bone adaptation and the characterization of the effects of mechanical loading and pharmaceutical treatment interventionsin vivo.
Growth responses ofCelosia argenteaL. in soils polluted with microplastics
Authors: Ikhajiagbe Beckley , Omoregie Gloria Omorowa , Adama Susan Ojonugwa , Esheya Kingsley Ume 
Published: January 2023

AbstractThis research was carried out to study the various toxic effects of microplastics on commercial leafy vegetableCelosia argenteaL. Plastics used in this experiment were obtained from heterogeneous sources from around different dumpsites in the University of Benin Ugbowo Campus. The plastics collected were grinded into three different bits and sizes, filtered and applied to the different plastic pots in the measurement of 5g, 10g and 20g respectively. The seeds ofCelosia argenteaL. was sown in the microplastic polluted soils and also the control Morphological characteristics were also observed and recorded and they include plant height, stem girth, leaf area amongst others. The plants were harvested after 52 days of observation and taken to the laboratory for heavy metal analysis. Results showed evidence of stunted growth, and chlorosis as compared to the control. Significant heavy metal accumulation was also recorded in the leaves and they include nickel, lead and cadmium.
The mechanosensitive ion channel Piezo1 contributes to ultrasound neuromodulation
Authors: Zhu Jiejun , Xian Quanxiang , Hou Xuandi , Wong Kin Fung , Zhu Tingting , Chen Zihao , He Dongming , Kala Shashwati , Jing Jianing , Wu Yong , Zhao Xinyi , Li Danni , Guo Jinghui , Qiu Zhihai , Sun Lei 
Published: January 2023

AbstractTranscranial low-intensity ultrasound is a promising neuromodulation modality, with the advantages of non-invasiveness, deep penetration, and high spatiotemporal accuracy. However, the underlying biological mechanism of ultrasonic neuromodulation remains unclear, hindering the development of efficacious treatments. Here, the well-known Piezo1, was studied through a conditional knockout mouse model as a major molecule for ultrasound neuromodulationex vivoandin vivo. We showed that Piezo1 knockout in the right motor cortex of mice significantly reduced ultrasound-induced neuronal calcium responses, limb movement and muscle EMG responses. We also detected higher Piezo1 in the central amygdala (CEA) which were found more sensitive to ultrasound stimulation than that of cortex. Knocking out the Piezo1 in CEA neurons showed a significant reduction of response under ultrasound stimulation while knocking out astrocytic Piezo1 showed no obvious changes in neuronal responses. Additionally, we excluded an auditory confound by monitoring auditory cortical activation and using smooth waveform ultrasound with randomized parameters to stimulate P1KO ipsilateral and contralateral regions of the same brain and recording evoked movement in the corresponding limb. Thus, we demonstrate that Piezo1 is functionally expressed in different brain regions, and that it is an important mediator of ultrasound neuromodulation in the brain, laying the ground for further mechanistic studies of ultrasound.
All-optical spatiotemporal mapping of ROS dynamics across mitochondrial microdomainsin situ
Authors: Koren Shon A. , Selim Nada A. , De La Rosa Lizbeth , Horn Jacob , Farooqi M. Arsalan , Wei Alicia Y. , Müller-Eigner Annika , Emerson Jacen , Johnson Gail V.W. , Wojtovich Andrew P. 
Published: January 2023

AbstractHydrogen peroxide (H2O2) functions as a second messenger to signal metabolic distress through highly compartmentalized production in mitochondria. The dynamics of ROS generation and diffusion between mitochondrial compartments and into the cytosol govern oxidative stress responses and pathology, though our understanding of these processes remains limited. Here, we couple the H2O2biosensor, HyPer7, with optogenetic stimulation of the ROS-generating protein KillerRed targeted into multiple mitochondrial microdomains. Single mitochondrial photogeneration of H2O2demonstrates the spatiotemporal dynamics of ROS diffusion and transient hyperfusion of mitochondria due to ROS. Measurement of microdomain-specific H2O2diffusion kinetics reveals directionally selective diffusion through mitochondrial microdomains. All-optical generation and detection of physiologically-relevant concentrations of H2O2between mitochondrial compartments provide a map of mitochondrial H2O2diffusion dynamicsin situ. These kinetic details of spatiotemporal ROS dynamics and inter-mitochondrial spreading forms a framework to understand the role of ROS in health and disease.
Elevated CO2alters photosynthesis, growth and susceptibility to powdery mildew of oak seedlings
Authors: Sanchez-Lucas Rosa , Mayoral Carolina , Raw Mark , Mousoraki Maria-Anna , Luna Estrella 
Published: January 2023

AbstractElevated CO2(eCO2) is a determinant factor of climate change and is known to alter plant processes such as physiology, growth and resistance to pathogens.Quercus robur, a tree species integrated in most forest regeneration strategies, shows high vulnerability to powdery mildew (PM) disease at the seedling stage. PM is present in most oak forests and it is considered a bottleneck for oak woodland regeneration. Our study aims to decipher the effect of eCO2 on plant responses to PM. Oak seedlings were grown in controlled environment at ambient (aCO2, ~ 400 ppm) and eCO2(~ 1000 ppm), and infected withErysiphe alphitoides, the causal agent of oak PM. Plant growth, physiological parameters and disease progression were monitored. In addition, to evaluate the effect of eCO2on induced resistance (IR), these parameters were assessed after treatments with IR elicitor β-aminobutyric acid (BABA). Our results show that eCO2increases photosynthetic rates and aerial growth but in contrast reduces root length. Importantly, under eCO2seedlings were more susceptible to PM. Treatments with BABA protected seedlings against PM, however, this effect was less pronounced under eCO2. Moreover, irrespectively of the concentration of CO2, BABA did not significantly change aerial growth but resulted in longer radicular systems, thus mitigating the effect of eCO2in root shortening. Our results demonstrate the impact of eCO2in plant physiology, growth and defence, and warrant further biomolecular studies to unravel the mechanisms by which eCO2increases oak seedling susceptibility to PM.