bluuebunny/crossref_metadata_2025_split huggingface dataset:
EGFR tyrosine kinase activity and Rab GTPases coordinate EGFR trafficking to regulate macrophage activation in sepsis
Authors: Zhang Xuedi , Chen Cuiping , Ling Chunxiu , Luo Shuhua , Xiong Ziying , Liu Xiaolei , Liao Chaoxiong , Xie Pengyun , Liu Youtan , Zhang Liangqing , Chen Zhanghui , Liu Zhifeng , Tang Jing 
Published: November 2022

AbstractEGFR phosphorylation is required for TLR4-mediated macrophage activation during sepsis. However, whether and how intracellular EGFR is transported during endotoxemia have largely been unknown. Here, we show that LPS promotes high levels cell surface expression of EGFR in macrophages through two different transport mechanisms. On one hand, Rab10 is required for EEA1-mediated the membrane translocation of EGFR from the Golgi. On the other hand, EGFR phosphorylation prevents its endocytosis in a kinase activity-dependent manner. Erlotinib, an EGFR tyrosine kinase inhibitor, significantly reduced membrane EGFR expression in LPS-activated macrophage. Mechanistically, upon LPS induced TLR4/EGFR phosphorylation, MAPK14 phosphorylated Rab7a at S72 impaired membrane receptor late endocytosis, which maintains EGFR membrane localization though blocking its lysosomal degradation. Meanwhile, Rab5a is also involved in the early endocytosis of EGFR. Subsequently, inhibition of EGFR phosphorylation switches M1 phenotype to M2 phenotype and alleviates sepsis-induced acute lung injury. Mechanistic study demonstrated that Erlotinib suppressed glycolysis-dependent M1 polarization via PKM2/HIF-1ɑ pathway and promoted M2 polarization through up-regulating PPARγ induced glutamine metabolism. Collectively, our data elucidated a more in-depth mechanism of macrophages activation, and provided stronger evidence supporting EGFR as a potential therapeutic target for the treatment of sepsis.
Splicing factor SRSF3 represses translation of p21cip1/waf1 mRNA
Authors: Kim Jeeho , Park Ra Young , Kee Younghoon , Jeong Sunjoo , Ohn Takbum 
Published: November 2022

AbstractSerine/arginine-rich splicing factor 3 (SRSF3) is an RNA binding protein that most often regulates gene expression at the splicing level. Although the role of SRSF3 in mRNA splicing in the nucleus is well known, its splicing-independent role outside of the nucleus is poorly understood. Here, we found that SRSF3 exerts a translational control of p21 mRNA. Depletion of SRSF3 induces cellular senescence and increases the expression of p21 independent of p53. Consistent with the expression patterns of SRSF3 and p21 mRNA in the TCGA database, SRSF3 knockdown increases the p21 mRNA level and its translation efficiency as well. SRSF3 physically associates with the 3′UTR region of p21 mRNA and the translational initiation factor, eIF4A1. Our study proposes a model in which SRSF3 regulates translation by interacting with eIF4A1 at the 3′UTR region of p21 mRNA. We also found that SRSF3 localizes to the cytoplasmic RNA granule along with eIF4A1, which may assist in translational repression therein. Thus, our results provide a new mode of regulation for p21 expression, a crucial regulator of the cell cycle and senescence, which occurs at the translational level and involves SRSF3.
CircFOXO3 protects against osteoarthritis by targeting its parental gene FOXO3 and activating PI3K/AKT-mediated autophagy
Authors: Zhao Chen , Li Xiaodong , Sun Guantong , Liu Pengcheng , Kong Keyu , Chen Xuzhuo , Yang Fei , Wang Xiaoqing 
Published: November 2022

AbstractOsteoarthritis (OA) is a degenerative joint disorder causing pain and functional disability. Emerging evidence reveals that circular RNAs (circRNAs) play essential roles in OA progression and development. This study aimed to investigate the role of a novel circRNA factor, circFOXO3, in the progression of OA and elucidate its underlying molecular mechanism. The function of circFOXO3 in OA and interaction between circFOXO3 and its downstream mRNA target, forkhead box O3 (FOXO3), were evaluated by western blot (WB), immunofluorescence (IF), RNA immunoprecipitation, reverse transcription-quantitative PCR (RT-qPCR), and fluorescence in situ hybridization (FISH). Upregulation of circFOXO3 and autophagic flux were detected both in vivo and in vitro by WB, transmission electron microscopy (TEM), IF, and immunohistochemistry (IHC). A mouse model of OA was also used to confirm the role of circFOXO3 in OA pathogenesis in vivo. Decreased expression of circFOXO3 in OA cartilage tissues was directly associated with excessive apoptosis and imbalance between anabolic and catabolic factors of the extracellular matrix (ECM). Mechanistically, circFOXO3 functioned in cartilage by targeting its parental gene FOXO3 and activating autophagy. Intra-articular injection of lentivirus-circFOXO3 alleviated OA in the mouse model. In conclusion, our results reveal the key role played by circFOXO3 in OA progression; circFOXO3 overexpression may alleviate apoptosis of chondrocytes and promote anabolism of the ECM via activation of FOXO3 and autophagy, providing a potentially effective novel therapeutic strategy for OA.
Necroptosis-mediated HMGB1 secretion of keratinocytes as a key step for inflammation development in contact hypersensitivity
Authors: Lian Ni , Chen Yujie , Chen Sihan , Xiao Ta , Song Changjun , Ke Yangying , Wei Xuecui , Gong Chunyan , Yu Hui , Gu Heng , Chen Qing , Li Min , Chen Xu 
Published: November 2022

AbstractKeratinocyte necroptosis (with proinflammatory characteristic) is required for epidermal damage in contact hypersensitivity (CHS). In DNCB-induced CHS mice model, we observed the aggravated keratinocyte death and increased phosphorylation level of MLKL, RIPK3 and RIPK1. However, CHS skin lesion did not present in keratinocyte-specific Mlkl knockout mice. We validated that MLKL-mediated keratinocyte necroptosis is required for epidermal damage in response to immune microenvironment in CHS. Moreover, MLKL-mediated necroptosis deficiency or inhibition resulted in blocking recruitment and activation of inflammatory cells in CHS via reducing HMGB1 release in keratinocytes. This study suggests that MLKL-mediated keratinocyte necroptosis functions as a self-amplified actor in inflammatory responses and could be considered as an effective therapeutic target. It proposes an innovative prospective that inhibiting keratinocyte necroptosis can prevent the development of epidermal damage in CHS.
Social interactions lead to motility-induced phase separation in fire ants
Authors: Anderson Caleb , Fernandez-Nieves Alberto 
Published: November 2022

AbstractCollections of fire ants are a form of active matter, as the ants use their internal metabolism to self-propel. In the absence of aligning interactions, theory and simulations predict that active matter with spatially dependent motility can undergo motility-induced phase separation. However, so far in experiments, the motility effects that drive this process have come from either crowding or an external parameter. Though fire ants are social insects that communicate and cooperate in nontrivial ways, we show that the effect of their interactions can also be understood within the framework of motility-induced phase separation. In this context, the slowing down of ants when they approach each other results in an effective attraction that can lead to space-filling clusters and an eventual formation of dynamical heterogeneities. These results illustrate that motility-induced phase separation can provide a unifying framework to rationalize the behavior of a wide variety of active matter systems.
Polarization-controlled tunable directional spin-driven photocurrents in a magnetic metamaterial with threefold rotational symmetry
Authors: Matsubara Masakazu , Kobayashi Takatsugu , Watanabe Hikaru , Yanase Youichi , Iwata Satoshi , Kato Takeshi 
Published: November 2022

AbstractFuture spintronics and quantum technologies will require a portfolio of techniques for manipulating electron spins in functional nanodevices. Especially, the establishment of the methods to control spin current is the key ingredient essential for the transfer and processing of information, enabling faster and low-energy operation. However, a universal method for manipulating spin currents with full-directional controllability and tunable magnitude has not been established. Here we show that an artificial material called a magnetic metamaterial (MM), which possesses a novel spintronic functionality not exhibited by the original substance, generates photo-driven ultrafast spin currents at room temperature via the magneto-photogalvanic effect. By tuning the polarization state of the excitation light, these spin currents can be directed with tunable magnitude along an arbitrary direction in the two-dimensional plane of the MM. This new concept may guide the design and creation of artificially engineered opto-spintronic functionalities beyond the limitations of conventional material science.
An epifluidic electronic patch with spiking sweat clearance for event-driven perspiration monitoring
Authors: Kim Sangha , Park Seongjin , Choi Jina , Hwang Wonseop , Kim Sunho , Choi In-Suk , Yi Hyunjung , Kwak Rhokyun 
Published: November 2022

AbstractSensory neurons generate spike patterns upon receiving external stimuli and encode key information to the spike patterns, enabling energy-efficient external information processing. Herein, we report an epifluidic electronic patch with spiking sweat clearance using a sensor containing a vertical sweat-collecting channel for event-driven, energy-efficient, long-term wireless monitoring of epidermal perspiration dynamics. Our sweat sensor contains nanomesh electrodes on its inner wall of the channel and unique sweat-clearing structures. During perspiration, repeated filling and abrupt emptying of the vertical sweat-collecting channel generate electrical spike patterns with the sweat rate and ionic conductivity proportional to the spike frequency and amplitude over a wide dynamic range and long time (> 8 h). With such ‘spiking’ sweat clearance and corresponding electronic spike patterns, the epifluidic wireless patch successfully decodes epidermal perspiration dynamics in an event-driven manner at different skin locations during exercise, consuming less than 0.6% of the energy required for continuous data transmission. Our patch could integrate various on-skin sensors and emerging edge computing technologies for energy-efficient, intelligent digital healthcare.
Multi-scale organization in communicating active matter
Authors: Ziepke Alexander , Maryshev Ivan , Aranson Igor S. , Frey Erwin 
Published: November 2022

AbstractThe emergence of collective motion among interacting, self-propelled agents is a central paradigm in non-equilibrium physics. Examples of such active matter range from swimming bacteria and cytoskeletal motility assays to synthetic self-propelled colloids and swarming microrobots. Remarkably, the aggregation capabilities of many of these systems rely on a theme as fundamental as it is ubiquitous in nature: communication. Despite its eminent importance, the role of communication in the collective organization of active systems is not yet fully understood. Here we report on the multi-scale self-organization of interacting self-propelled agents that locally process information transmitted by chemical signals. We show that this communication capacity dramatically expands their ability to form complex structures, allowing them to self-organize through a series of collective dynamical states at multiple hierarchical levels. Our findings provide insights into the role of self-sustained signal processing for self-organization in biological systems and open routes to applications using chemically driven colloids or microrobots.
SAMHD1 deacetylation by SIRT1 promotes DNA end resection by facilitating DNA binding at double-strand breaks
Authors: Kapoor-Vazirani Priya , Rath Sandip K. , Liu Xu , Shu Zhen , Bowen Nicole E. , Chen Yitong , Haji-Seyed-Javadi Ramona , Daddacha Waaqo , Minten Elizabeth V. , Danelia Diana , Farchi Daniela , Duong Duc M. , Seyfried Nicholas T. , Deng Xingming , Ortlund Eric A. , Kim Baek , Yu David S. 
Published: November 2022

AbstractSterile alpha motif and HD domain-containing protein 1 (SAMHD1) has a dNTPase-independent function in promoting DNA end resection to facilitate DNA double-strand break (DSB) repair by homologous recombination (HR); however, it is not known if upstream signaling events govern this activity. Here, we show that SAMHD1 is deacetylated by the SIRT1 sirtuin deacetylase, facilitating its binding with ssDNA at DSBs, to promote DNA end resection and HR. SIRT1 complexes with and deacetylates SAMHD1 at conserved lysine 354 (K354) specifically in response to DSBs. K354 deacetylation by SIRT1 promotes DNA end resection and HR but not SAMHD1 tetramerization or dNTPase activity. Mechanistically, K354 deacetylation by SIRT1 promotes SAMHD1 recruitment to DSBs and binding to ssDNA at DSBs, which in turn facilitates CtIP ssDNA binding, leading to promotion of genome integrity. These findings define a mechanism governing the dNTPase-independent resection function of SAMHD1 by SIRT1 deacetylation in promoting HR and genome stability.
Molecular differences between younger versus older ER-positive and HER2-negative breast cancers
Authors: Qing Tao , Karn Thomas , Rozenblit Mariya , Foldi Julia , Marczyk Michal , Shan Naing Lin , Blenman Kim , Holtrich Uwe , Kalinsky Kevin , Meric-Bernstam Funda , Pusztai Lajos 
Published: November 2022

AbstractThe RxPONDER and TAILORx trials demonstrated benefit from adjuvant chemotherapy in patients age ≤ 50 with node-positive breast cancer and Recurrence Score (RS) 0–26, and in node-negative disease with RS 16–25, respectively, but no benefit in older women with the same clinical features. We analyzed transcriptomic and genomic data of ER+/HER2− breast cancers with in silico RS < 26 from TCGA (n = 530), two microarray cohorts (A: n = 865; B: n = 609), the METABRIC (n = 867), and the SCAN-B (n = 1636) datasets. There was no difference in proliferation-related gene expression between age groups. Older patients had higher mutation burden and more frequent ESR1 copy number gain, but lower frequency of GATA3 mutations. Younger patients had higher rate of ESR1 copy number loss. In all datasets, younger patients had significantly lower mRNA expression of ESR1 and ER-associated genes, and higher expression of immune-related genes. The ER- and immune-related gene signatures showed negative correlation and defined three subpopulations in younger women: immune-high/ER-low, immune-intermediate/ER-intermediate, and immune-low/ER-intermediate. We hypothesize that in immune-high cancers, the cytotoxic effect of chemotherapy may drive the benefit, whereas in immune-low/ER-intermediate cancers chemotherapy induced ovarian suppression may play important role.
Microfluidics-integrated spaceflight hardware for measuring muscle strength of Caenorhabditis elegans on the International Space Station
Authors: Soni Purushottam , Anupom Taslim , Lesanpezeshki Leila , Rahman Mizanur , Hewitt Jennifer E. , Vellone Matthew , Stodieck Louis , Blawzdziewicz Jerzy , Szewczyk Nathaniel J. , Vanapalli Siva A. 
Published: November 2022

AbstractCaenorhabditis elegansis a low-cost genetic model that has been flown to the International Space Station to investigate the influence of microgravity on changes in the expression of genes involved in muscle maintenance. These studies showed that genes that encode muscle attachment complexes have decreased expression under microgravity. However, it remains to be answered whether the decreased expression leads to concomitant changes in animal muscle strength, specifically across multiple generations. We recently reported the NemaFlex microfluidic device for the measurement of muscle strength ofC. elegans(Rahman et al., Lab Chip, 2018). In this study, we redesign our original NemaFlex device and integrate it with flow control hardware for spaceflight investigations considering mixed animal culture, constraints on astronaut time, crew safety, and on-orbit operations. The technical advances we have made include (i) a microfluidic device design that allows animals of a given size to be sorted from unsynchronized cultures and housed in individual chambers, (ii) a fluid handling protocol for injecting the suspension of animals into the microfluidic device that prevents channel clogging, introduction of bubbles, and crowding of animals in the chambers, and (iii) a custom-built worm-loading apparatus interfaced with the microfluidic device that allows easy manipulation of the worm suspension and prevents fluid leakage into the surrounding environment. Collectively, these technical advances enabled the development of new microfluidics-integrated hardware for spaceflight studies inC. elegans. Finally, we report Earth-based validation studies to test this new hardware, which has led to it being flown to the International Space Station.
Feasibility of novel adult tuberculosis vaccination in South Africa: a cost-effectiveness and budget impact analysis
Authors: Jayawardana Sahan , Weerasuriya Chathika K. , Pelzer Puck T. , Seeley Janet , Harris Rebecca C. , Tameris Michele , Tait Dereck , White Richard G. , Asaria Miqdad 
Published: November 2022

AbstractEarly trials of novel vaccines against tuberculosis (TB) in adults have suggested substantial protection against TB. However, little is known about the feasibility and affordability of rolling out such vaccines in practice. We conducted expert interviews to identify plausible vaccination implementation strategies for the novel M72/AS01E vaccine candidate. The strategies were defined in terms of target population, coverage, vaccination schedule and delivery mode. We modelled these strategies to estimate long-term resource requirements and health benefits arising from vaccination over 2025–2050. We presented these to experts who excluded strategies that were deemed infeasible, and estimated cost-effectiveness and budget impact for each remaining strategy. The four strategies modelled combined target populations: either everyone aged 18–50, or all adults living with HIV, with delivery strategies: either a mass campaign followed by routine vaccination of 18-year olds, or two mass campaigns 10 years apart. Delivering two mass campaigns to all 18–50-year olds was found to be the most cost-effective strategy conferring the greatest net health benefit of 1.2 million DALYs averted having a probability of being cost-effective of 65–70%. This strategy required 38 million vaccine courses to be delivered at a cost of USD 507 million, reducing TB-related costs by USD 184 million while increasing ART costs by USD 79 million. A suitably designed adult TB vaccination programme built around novel TB vaccines is likely to be cost-effective and affordable given the resource and budget constraints in South Africa.
Intron-encoded cistronic transcripts for minimally invasive monitoring of coding and non-coding RNAs
Authors: Truong Dong-Jiunn Jeffery , Armbrust Niklas , Geilenkeuser Julian , Lederer Eva-Maria , Santl Tobias Heinrich , Beyer Maren , Ittermann Sebastian , Steinmaßl Emily , Dyka Mariya , Raffl Gerald , Phlairaharn Teeradon , Greisle Tobias , Živanić Milica , Grosch Markus , Drukker Micha , Westmeyer Gil Gregor 
Published: November 2022

AbstractDespite their fundamental role in assessing (patho)physiological cell states, conventional gene reporters can follow gene expression but leave scars on the proteins or substantially alter the mature messenger RNA. Multi-time-point measurements of non-coding RNAs are currently impossible without modifying their nucleotide sequence, which can alter their native function, half-life and localization. Thus, we developed the intron-encoded scarless programmable extranuclear cistronic transcript (INSPECT) as a minimally invasive transcriptional reporter embedded within an intron of a gene of interest. Post-transcriptional excision of INSPECT results in the mature endogenous RNA without sequence alterations and an additional engineered transcript that leaves the nucleus by hijacking the nuclear export machinery for subsequent translation into a reporter or effector protein. We showcase its use in monitoring interleukin-2 (IL2) after T cell activation and tracking the transcriptional dynamics of the long non-coding RNA (lncRNA) NEAT1 during CRISPR interference-mediated perturbation. INSPECT is a method for monitoring gene transcription without altering the mature lncRNA or messenger RNA of the target of interest.
MINSTED nanoscopy enters the Ångström localization range
Authors: Weber Michael , von der Emde Henrik , Leutenegger Marcel , Gunkel Philip , Sambandan Sivakumar , Khan Taukeer A. , Keller-Findeisen Jan , Cordes Volker C. , Hell Stefan W. 
Published: November 2022

AbstractSuper-resolution techniques have achieved localization precisions in the nanometer regime. Here we report all-optical, room temperature localization of fluorophores with precision in the Ångström range. We built on the concept of MINSTED nanoscopy where precision is increased by encircling the fluorophore with the low-intensity central region of a stimulated emission depletion (STED) donut beam while constantly increasing the absolute donut power. By blue-shifting the STED beam and separating fluorophores by on/off switching, individual fluorophores bound to a DNA strand are localized with σ = 4.7 Å, corresponding to a fraction of the fluorophore size, with only 2,000 detected photons. MINSTED fluorescence nanoscopy with single-digit nanometer resolution is exemplified by imaging nuclear pore complexes and the distribution of nuclear lamin in mammalian cells labeled by transient DNA hybridization. Because our experiments yield a localization precision σ = 2.3 Å, estimated for 10,000 detected photons, we anticipate that MINSTED will open up new areas of application in the study of macromolecular complexes in cells.
A western United States snow reanalysis dataset over the Landsat era from water years 1985 to 2021
Authors: Fang Yiwen , Liu Yufei , Margulis Steven A. 
Published: November 2022

AbstractWater stored in mountain snowpacks (i.e., snow water equivalent, SWE) represents an important but poorly characterized component of the terrestrial water cycle. The Western United States snow reanalysis (WUS–SR) dataset is novel in its combination of spatial resolution (~500 m), spatial extent (31°–49° N; 102°–125° W), and temporal continuity (daily over 1985–2021). WUS–SR is generated using a Bayesian framework with model-based snow estimates updated through the assimilation of cloud-free Landsat fractional snow-covered area observations. Over the WUS, the peak SWE verification with independent in situ measurements show correlation coefficient, mean difference (MD), and root mean squared difference (RMSD) of 0.77, −0.15 m, and 0.28 m, respectively. The effects of forest cover and Landsat image availability on peak SWE are assessed. WUS–SR peak SWE is well correlated (ranging from 0.75 to 0.91) against independent lidar-derived SWE taken near April 1st, with MD <0.15 m and RMSD <0.38 m. The dataset is useful for characterizing WUS mountain snow storage, and ultimately for improving snow-derived water resources management.