bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling Chlamydia and HPV co-infection in patient-derived ectocervix organoids reveals distinct cellular reprogramming
Authors: Koster Stefanie , Gurumurthy Rajendra Kumar , Kumar Naveen , Prakash Pon Ganish , Dhanraj Jayabhuvaneshwari , Bayer Sofia , Berger Hilmar , Kurian Shilpa Mary , Drabkina Marina , Mollenkopf Hans-Joachim , Goosmann Christian , Brinkmann Volker , Nagel Zachary , Mangler Mandy , Meyer Thomas F. , Chumduri Cindrilla 
Published: February 2022

AbstractCoinfections with pathogenic microbes continually confront cervical mucosa, yet their implications in pathogenesis remain unclear. Lack of in-vitro models recapitulating cervical epithelium has been a bottleneck to study coinfections. Using patient-derived ectocervical organoids, we systematically modeled individual and coinfection dynamics of Human papillomavirus (HPV)16 E6E7 and Chlamydia, associated with carcinogenesis. The ectocervical stem cells were genetically manipulated to introduce E6E7 oncogenes to mimic HPV16 integration. Organoids from these stem cells develop the characteristics of precancerous lesions while retaining the self-renewal capacity and organize into mature stratified epithelium similar to healthy organoids. HPV16 E6E7 interferes with Chlamydia development and induces persistence. Unique transcriptional and post-translational responses induced by Chlamydia and HPV lead to distinct reprogramming of host cell processes. Strikingly, Chlamydia impedes HPV-induced mechanisms that maintain cellular and genome integrity, including mismatch repair in the stem cells. Together, our study employing organoids demonstrates the hazard of multiple infections and the unique cellular microenvironment they create, potentially contributing to neoplastic progression.
AP-4-mediated axonal transport controls endocannabinoid production in neurons
Authors: Davies Alexandra K. , Alecu Julian E. , Ziegler Marvin , Vasilopoulou Catherine G. , Merciai Fabrizio , Jumo Hellen , Afshar-Saber Wardiya , Sahin Mustafa , Ebrahimi-Fakhari Darius , Borner Georg H. H. 
Published: February 2022

AbstractThe adaptor protein complex AP-4 mediates anterograde axonal transport and is essential for axon health. AP-4-deficient patients suffer from a severe neurodevelopmental and neurodegenerative disorder. Here we identify DAGLB (diacylglycerol lipase-beta), a key enzyme for generation of the endocannabinoid 2-AG (2-arachidonoylglycerol), as a cargo of AP-4 vesicles. During normal development, DAGLB is targeted to the axon, where 2-AG signalling drives axonal growth. We show that DAGLB accumulates at the trans-Golgi network of AP-4-deficient cells, that axonal DAGLB levels are reduced in neurons from a patient with AP-4 deficiency, and that 2-AG levels are reduced in the brains of AP-4 knockout mice. Importantly, we demonstrate that neurite growth defects of AP-4-deficient neurons are rescued by inhibition of MGLL (monoacylglycerol lipase), the enzyme responsible for 2-AG hydrolysis. Our study supports a new model for AP-4 deficiency syndrome in which axon growth defects arise through spatial dysregulation of endocannabinoid signalling.
Inhibition of SRP-dependent protein secretion by the bacterial alarmone (p)ppGpp
Authors: Czech Laura , Mais Christopher-Nils , Kratzat Hanna , Sarmah Pinku , Giammarinaro Pietro , Freibert Sven-Andreas , Esser Hanna Folke , Musial Joanna , Berninghausen Otto , Steinchen Wieland , Beckmann Roland , Koch Hans-Georg , Bange Gert 
Published: February 2022

AbstractThe stringent response enables bacteria to respond to nutrient limitation and other stress conditions through production of the nucleotide-based second messengers ppGpp and pppGpp, collectively known as (p)ppGpp. Here, we report that (p)ppGpp inhibits the signal recognition particle (SRP)-dependent protein targeting pathway, which is essential for membrane protein biogenesis and protein secretion. More specifically, (p)ppGpp binds to the SRP GTPases Ffh and FtsY, and inhibits the formation of the SRP receptor-targeting complex, which is central for the coordinated binding of the translating ribosome to the SecYEG translocon. Cryo-EM analysis of SRP bound to translating ribosomes suggests that (p)ppGpp may induce a distinct conformational stabilization of the NG domain of Ffh and FtsY in Bacillus subtilis but not in E. coli.
Structural basis of adenylyl cyclase 9 activation
Authors: Qi Chao , Lavriha Pia , Mehta Ved , Khanppnavar Basavraj , Mohammed Inayathulla , Li Yong , Lazaratos Michalis , Schaefer Jonas V. , Dreier Birgit , Plückthun Andreas , Bondar Ana-Nicoleta , Dessauer Carmen W. , Korkhov Volodymyr M. 
Published: February 2022

AbstractAdenylyl cyclase 9 (AC9) is a membrane-bound enzyme that converts ATP into cAMP. The enzyme is weakly activated by forskolin, fully activated by the G protein Gαs subunit and is autoinhibited by the AC9 C-terminus. Although our recent structural studies of the AC9-Gαs complex provided the framework for understanding AC9 autoinhibition, the conformational changes that AC9 undergoes in response to activator binding remains poorly understood. Here, we present the cryo-EM structures of AC9 in several distinct states: (i) AC9 bound to a nucleotide inhibitor MANT-GTP, (ii) bound to an artificial activator (DARPin C4) and MANT-GTP, (iii) bound to DARPin C4 and a nucleotide analogue ATPαS, (iv) bound to Gαs and MANT-GTP. The artificial activator DARPin C4 partially activates AC9 by binding at a site that overlaps with the Gαs binding site. Together with the previously observed occluded and forskolin-bound conformations, structural comparisons of AC9 in the four conformations described here show that secondary structure rearrangements in the region surrounding the forskolin binding site are essential for AC9 activation.
Overall photosynthesis of H2O2 by an inorganic semiconductor
Authors: Liu Tian , Pan Zhenhua , Vequizo Junie Jhon M. , Kato Kosaku , Wu Binbin , Yamakata Akira , Katayama Kenji , Chen Baoliang , Chu Chiheng , Domen Kazunari 
Published: February 2022

AbstractArtificial photosynthesis of H2O2 using earth-abundant water and oxygen is a promising approach to achieve scalable and cost-effective solar fuel production. Recent studies on this topic have made significant progress, yet are mainly focused on using organic polymers. This set of photocatalysts is susceptible to potent oxidants (e.g. hydroxyl radical) that are inevitably formed during H2O2 generation. Here, we report an inorganic Mo-doped faceted BiVO4 (Mo:BiVO4) system that is resistant to radical oxidation and exhibits a high overall H2O2 photosynthesis efficiency among inorganic photocatalysts, with an apparent quantum yield of 1.2% and a solar-to-chemical conversion efficiency of 0.29% at full spectrum, as well as an apparent quantum yield of 5.8% at 420 nm. The surface-reaction kinetics and selectivity of Mo:BiVO4 were tuned by precisely loading CoOx and Pd on {110} and {010} facets, respectively. Time-resolved spectroscopic investigations of photocarriers suggest that depositing select cocatalysts on distinct facet tailored the interfacial energetics between {110} and {010} facets and enhanced charge separation in Mo:BiVO4, therefore overcoming a key challenge in developing efficient inorganic photocatalysts. The promising H2O2 generation efficiency achieved by delicate design of catalyst spatial and electronic structures sheds light on applying robust inorganic particulate photocatalysts to artificial photosynthesis of H2O2.
Rejuvenation of plasticity via deformation graining in magnesium
Authors: Liu Bo-Yu , Zhang Zhen , Liu Fei , Yang Nan , Li Bin , Chen Peng , Wang Yu , Peng Jin-Hua , Li Ju , Ma En , Shan Zhi-Wei 
Published: February 2022

AbstractMagnesium, the lightest structural metal, usually exhibits limited ambient plasticity when compressed along its crystallographic c-axis (the “hard” orientation of magnesium). Here we report large plasticity in c-axis compression of submicron magnesium single crystal achieved by a dual-stage deformation. We show that when the plastic flow gradually strain-hardens the magnesium crystal to gigapascal level, at which point dislocation mediated plasticity is nearly exhausted, the sample instantly pancakes without fracture, accompanying a conversion of the initial single crystal into multiple grains that roughly share a common rotation axis. Atomic-scale characterization, crystallographic analyses and molecular dynamics simulations indicate that the new grains can form via transformation of pyramidal to basal planes. We categorize this grain formation as “deformation graining”. The formation of new grains rejuvenates massive dislocation slip and deformation twinning to enable large plastic strains.
Enhancing hydrovoltaic power generation through heat conduction effects
Authors: Li Lianhui , Feng Sijia , Bai Yuanyuan , Yang Xianqing , Liu Mengyuan , Hao Mingming , Wang Shuqi , Wu Yue , Sun Fuqin , Liu Zheng , Zhang Ting 
Published: February 2022

AbstractRestricted ambient temperature and slow heat replenishment in the phase transition of water molecules severely limit the performance of the evaporation-induced hydrovoltaic generators. Here we demonstrate a heat conduction effect enhanced hydrovoltaic power generator by integrating a flexible ionic thermoelectric gelatin material with a porous dual-size Al2O3 hydrovoltaic generator. In the hybrid heat conduction effect enhanced hydrovoltaic power generator, the ionic thermoelectric gelatin material can effectively improve the heat conduction between hydrovoltaic generator and near environment, thus increasing the water evaporation rate to improve the output voltage. Synergistically, hydrovoltaic generator part with continuous water evaporation can induce a constant temperature difference for the thermoelectric generator. Moreover, the system can efficiently achieve solar-to-thermal conversion to raise the temperature difference, accompanied by a stable open circuit voltage of 6.4 V for the hydrovoltaic generator module, the highest value yet.
Transcriptional repression of estrogen receptor alpha by YAP reveals the Hippo pathway as therapeutic target for ER+ breast cancer
Authors: Ma Shenghong , Tang Tracy , Probst Gary , Konradi Andrei , Jin Chunyu , Li Fulong , Gutkind J. Silvio , Fu Xiang-Dong , Guan Kun-Liang 
Published: February 2022

AbstractExtensive knowledge has been gained on the transcription network controlled by ERα, however, the mechanism underlying ESR1 (encoding ERα) expression is less understood. We recently discovered that the Hippo pathway is required for the proper expression of ESR1. YAP/TAZ are transcription coactivators that are phosphorylated and inhibited by the Hippo pathway kinase LATS. Here we delineated the molecular mechanisms underlying ESR1 transcription repression by the Hippo pathway. Mechanistically, YAP binds to TEAD to increase local chromatin accessibility to stimulate transcription of nearby genes. Among the YAP target genes, Vestigial-Like Protein 3 (VGLL3) competes with YAP/TAZ for binding to TEAD transcription factor and recruits the NCOR2/SMRT repressor to the super-enhancer of ESR1 gene, leading to epigenetic alteration and transcriptional silencing. We developed a potent LATS inhibitor VT02956. Targeting the Hippo pathway by VT02956 represses ESR1 expression and inhibits the growth of ER+ breast cancer cells as well as patient-derived tumour organoids. Moreover, histone deacetylase inhibitors, such as Entinostat, induce VGLL3 expression to inhibit ER+ breast cancer cells. Our study suggests LATS as unexpected cancer therapeutic targets, especially for endocrine-resistant breast cancers.
Molecular and cellular insight into Escherichia coli SslE and its role during biofilm maturation
Authors: Corsini Paula M. , Wang Sunjun , Rehman Saima , Fenn Katherine , Sagar Amin , Sirovica Slobodan , Cleaver Leanne , Edwards-Gayle Charlotte J. C. , Mastroianni Giulia , Dorgan Ben , Sewell Lee M. , Lynham Steven , Iuga Dinu , Franks W. Trent , Jarvis James , Carpenter Guy H. , Curtis Michael. A. , Bernadó Pau , Darbari Vidya C. , Garnett James A. 
Published: February 2022

AbstractEscherichia coliis a Gram-negative bacterium that colonises the human intestine and virulent strains can cause severe diarrhoeal and extraintestinal diseases. The protein SslE is secreted by a range of pathogenic and commensalE. colistrains. It can degrade mucins in the intestine, promotes biofilm maturation and it is a major determinant of infection in virulent strains, although how it carries out these functions is not well understood. Here, we examine SslE from the commensalE. coliWaksman and BL21 (DE3) strains and the enterotoxigenic H10407 and enteropathogenic E2348/69 strains. We reveal that SslE has a unique and dynamic structure in solution and in response to acidification within mature biofilms it can form a unique aggregate with amyloid-like properties. Furthermore, we show that both SslE monomers and aggregates bind DNA in vitro and co-localise with extracellular DNA (eDNA) in mature biofilms, and SslE aggregates may also associate with cellulose under certain conditions. Our results suggest that interactions between SslE and eDNA are important for biofilm maturation in manyE. colistrains and SslE may also be a factor that drives biofilm formation in other SslE-secreting bacteria.
Spatial analysis connects excess water pollution discharge, industrial production, and consumption at the sectoral level
Authors: Hou Siyu , Zhao Xu , Liu Yu , Tillotson Martin R. , Weng Shenglin , Wang Hua , Li Yiping , Liu Baoyin , Feng Kuishuang , Zhang Ning 
Published: February 2022

AbstractLinking of ‘consumption-industrial production-surface water deterioration’ is essential for industrialised economies to understand the mechanism of industrial water pollution. However, such a connection may mislead policy decisions if sectoral details are lacking. This study investigated excess pollution discharge from 11,094 industrial enterprises comprising 22 economic sectors through setting discharge thresholds on 1338 water function zones in Jiangsu Province, the most industrialised province in China. We further evaluated the contribution of final consumption in Chinese provinces to excess pollution discharge in Jiangsu via a national multi-region input–output table. Notably, despite typically heavy polluting sectors contributing the maximum excess pollution discharge, high-tech manufacturing sectors had a higher level of risk for excess pollution discharge. This was attributed to the spatial agglomeration of these sectors, with enterprises typically located in industrial parks. The increasing final consumption of specific sectors in both Jiangsu and other provinces may further drive excess pollution discharge in Jiangsu.
Commensal Pseudomonas strains facilitate protective response against pathogens in the host plant
Authors: Shalev Or , Karasov Talia L. , Lundberg Derek S. , Ashkenazy Haim , Pramoj Na Ayutthaya Pratchaya , Weigel Detlef 
Published: February 2022

AbstractThe community structure in the plant-associated microbiome depends collectively on host–microbe, microbe–microbe and host–microbe–microbe interactions. The ensemble of interactions between the host and microbial consortia may lead to outcomes that are not easily predicted from pairwise interactions. Plant–microbe–microbe interactions are important to plant health but could depend on both host and microbe strain variation. Here we study interactions between groups of naturally co-existing commensal and pathogenic Pseudomonas strains in the Arabidopsis thaliana phyllosphere. We find that commensal Pseudomonas prompt a host response that leads to selective inhibition of a specific pathogenic lineage, resulting in plant protection. The extent of protection depends on plant genotype, supporting that these effects are host-mediated. Strain-specific effects are also demonstrated by one individual Pseudomonas isolate eluding the plant protection provided by commensals. Our work highlights how within-species genetic differences in both hosts and microbes can affect host–microbe–microbe dynamics.
Influence of extracellular protein isolated from fish gut associated bacteria as an enhancer of growth and innate immune system in Mugil cephalus
Authors: Thirunavukkarasu Rajasekar , Pandi Priyadarshin , Balaraman Deivasigamani , Albalawi Fadwa , Ahmad Naushad , Panagal Mani , Nageswara Rao Tentu , Subramanian Kumaran , George Edward Gnana Jothi , Rajan MaryShamya Arockia , Renuga Pugazhvendan Sampath , Aruni Wilson , AlOmar Suliman Yousef 
Published: February 2022

AbstractThe cultural microbiomes of 27 bacteria colonies were isolated from Mugil cephalus for analysis of the antibacterial and antagonistic activities. A potent probiotic bacterium was characterized using16S r RNA sequencing. The potent strain was added to fish diet to perform the challenge test and to study the growth and immunological parameter. The extracellular proteins from the probiotic were collected and characterized using MALDI TOF/TOF. Out of G27, G9 strain inhibited all the five pathogenic strains. An isolated bacterium was identified as Bacillus subtilis PRBD09 with accession number KF765648. After 35 days of feeding period B. subtilis PRBD09 enhance the both cellular and humoral immune responses, which responsible for survive of the Mugil cephalus against Aeromonas hydrophila infection. The MALDI TOF sample 08 and 09 were recognized as hypothetical proteins based on the MALDI TOF sample. A cytidinedeaminase was found in samples 10, 11, and 12. Extracellular proteins may be involved for the immunological increase in Mugil cephalus against Aeromonas hydrophila, according to the current research.
Online learning for orientation estimation during translation in an insect ring attractor network
Authors: Robinson Brian S. , Norman-Tenazas Raphael , Cervantes Martha , Symonette Danilo , Johnson Erik C. , Joyce Justin , Rivlin Patricia K. , Hwang Grace M. , Zhang Kechen , Gray-Roncal William 
Published: February 2022

AbstractInsect neural systems are a promising source of inspiration for new navigation algorithms, especially on low size, weight, and power platforms. There have been unprecedented recent neuroscience breakthroughs withDrosophilain behavioral and neural imaging experiments as well as the mapping of detailed connectivity of neural structures. General mechanisms for learning orientation in the central complex (CX) ofDrosophilahave been investigated previously; however, it is unclear how these underlying mechanisms extend to cases where there is translation through an environment (beyond only rotation), which is critical for navigation in robotic systems. Here, we develop a CX neural connectivity-constrained model that performs sensor fusion, as well as unsupervised learning of visual features for path integration; we demonstrate the viability of this circuit for use in robotic systems in simulated and physical environments. Furthermore, we propose a theoretical understanding of how distributed online unsupervised network weight modification can be leveraged for learning in a trajectory through an environment by minimizing orientation estimation error. Overall, our results may enable a new class of CX-derived low power robotic navigation algorithms and lead to testable predictions to inform future neuroscience experiments.
Hidden mechanical weaknesses within lava domes provided by buried high-porosity hydrothermal alteration zones
Authors: Darmawan Herlan , Troll Valentin R. , Walter Thomas R. , Deegan Frances M. , Geiger Harri , Heap Michael J. , Seraphine Nadhirah , Harris Chris , Humaida Hanik , Müller Daniel 
Published: February 2022

AbstractCatastrophic lava dome collapse is considered an unpredictable volcanic hazard because the physical properties, stress conditions, and internal structure of lava domes are not well understood and can change rapidly through time. To explain the locations of dome instabilities at Merapi volcano, Indonesia, we combined geochemical and mineralogical analyses, rock physical property measurements, drone-based photogrammetry, and geoinformatics. We show that a horseshoe-shaped alteration zone that formed in 2014 was subsequently buried by renewed lava extrusion in 2018. Drone data, as well as geomechanical, mineralogical, and oxygen isotope data suggest that this zone is characterized by high-porosity hydrothermally altered materials that are mechanically weak. We additionally show that the new lava dome is currently collapsing along this now-hidden weak alteration zone, highlighting that a detailed understanding of dome architecture, made possible using the monitoring techniques employed here, is essential for assessing hazards associated with dome and edifice failure at volcanoes worldwide.
COVID-rate: an automated framework for segmentation of COVID-19 lesions from chest CT images
Authors: Enshaei Nastaran , Oikonomou Anastasia , Rafiee Moezedin Javad , Afshar Parnian , Heidarian Shahin , Mohammadi Arash , Plataniotis Konstantinos N. , Naderkhani Farnoosh 
Published: February 2022

AbstractNovel Coronavirus disease (COVID-19) is a highly contagious respiratory infection that has had devastating effects on the world. Recently, new COVID-19 variants are emerging making the situation more challenging and threatening. Evaluation and quantification of COVID-19 lung abnormalities based on chest Computed Tomography (CT) images can help determining the disease stage, efficiently allocating limited healthcare resources, and making informed treatment decisions. During pandemic era, however, visual assessment and quantification of COVID-19 lung lesions by expert radiologists become expensive and prone to error, which raises an urgent quest to develop practical autonomous solutions. In this context, first, the paper introduces an open-access COVID-19 CT segmentation dataset containing 433 CT images from 82 patients that have been annotated by an expert radiologist. Second, a Deep Neural Network (DNN)-based framework is proposed, referred to as the $$\text {COVID-Rate}$$
COVID-Rate
, that autonomously segments lung abnormalities associated with COVID-19 from chest CT images. Performance of the proposed $$\text {COVID-Rate}$$
COVID-Rate
framework is evaluated through several experiments based on the introduced and external datasets. Third, an unsupervised enhancement approach is introduced that can reduce the gap between the training set and test set and improve the model generalization. The enhanced results show a dice score of 0.8069 and specificity and sensitivity of 0.9969 and 0.8354, respectively. Furthermore, the results indicate that the $$\text {COVID-Rate}$$
COVID-Rate
model can efficiently segment COVID-19 lesions in both 2D CT images and whole lung volumes. Results on the external dataset illustrate generalization capabilities of the $$\text {COVID-Rate}$$
COVID-Rate
model to CT images obtained from a different scanner.