bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interdecadal Modulation of ENSO‐Related Anomalous Equatorial Intermediate Currents in the Western Pacific by the PDO
Authors: Ma Qiang , Wang Jianing , Wang Fan , Lyu Yilong , Zhang Zhixiang 
Published: March 2022

AbstractAs the most prominent decadal variability in the Pacific Ocean, the Pacific Decadal Oscillation (PDO) can influence the El Niño‐Southern Oscillation‐related atmospheric and upper oceanic motions. Based on results from ocean reanalysis products and linear continuously stratified model experiments, we reveal that the PDO can further extend its interdecadal modulation effect to the equatorial intermediate currents below the thermocline. For the maximum El Niño‐related intermediate eastward transport anomaly in the western Pacific, its magnitude during the warm PDO is nearly twice as large as that during the cold PDO, and its occurrence time in the warm PDO leads that in the cold PDO by about 2 months. Such modulation is achieved through westward and downward propagation of the reflected Kelvin‐to‐Rossby waves, triggered by enhanced and eastward‐displaced anomalous westerly wind. The decisive wind forcing region for the modulation is located over the equatorial central Pacific of 5°S–5°N and 180°–140°W.
Cav3.1-driven bursting firing in ventromedial hypothalamic neurons exerts dual control of anxiety-like behavior and energy expenditure
Authors: Shao Jie , Gao Da-Shuang , Liu Yun-Hui , Chen Shan-Ping , Liu Nian , Zhang Lu , Zhou Xin-Yi , Xiao Qian , Wang Li-Ping , Hu Hai-Lan , Yang Fan 
Published: March 2022

AbstractThe central nervous system has evolved to coordinate the regulation of both the behavior response to the external environment and homeostasis of energy expenditure. Recent studies have indicated the dorsomedial ventromedial hypothalamus (dmVMH) as an important hub that regulates both innate behavior and energy homeostasis for coping stress. However, how dmVMH neurons control neuronal firing pattern to regulate chronic stress-induced anxiety and energy expenditure remains poorly understood. Here, we found enhanced neuronal activity in VMH after chronic stress, which is mainly induced by increased proportion of burst firing neurons. This enhancement of VMH burst firing is predominantly mediated by Cav3.1 expression. Optogenetically evoked burst firing of dmVMH neurons induced anxiety-like behavior, shifted the respiratory exchange ratio toward fat oxidation, and decreased food intake, while knockdown of Cav3.1 in the dmVMH had the opposite effects, suggested that Cav 3.1 as a crucial regulator. Interestingly, we found that fluoxetine (anxiolytics) could block the increase of Cav3.1 expression to inhibit the burst firing, and then rescued the anxiety-like behaviors and energy expenditure changes. Collectively, our study first revealed an important role of Cav3.1-driven bursting firing of dmVMH neurons in the control of anxiety-like behavior and energy expenditure, and provided potential therapeutic targets for treating the chronic stress-induced emotional malfunction and metabolism disorders.
UPF1 contributes to the maintenance of endometrial cancer stem cell phenotype by stabilizing LINC00963
Authors: Chen Hao , Ma Jian , Kong Fanfei , Song Ning , Wang Cuicui , Ma Xiaoxin 
Published: March 2022

AbstractEndometrial cancer stem cells (ECSCs) play a vital role in endometrial cancer (EC) metastasis, relapse, and chemoresistance. However, the molecular mechanisms that sustain ECSCs remain elusive. Here, we showed that the expression of UPF1 was upregulated in EC tissues and ECSCs and correlated with poor clinicopathological characteristics. UPF1 silencing suppressed ECSC hallmarks, such as sphere formation ability, carboplatin resistance, migration and invasion, and cell cycle progression. UPF1 regulated the behavior and fate of ECSCs by stabilizing LINC00963. LINC00963 further shares the same miRNA response element with the core transcription factor SOX2 and relieved the suppression of SOX2 by miR-508-5p in self-renewing ECSCs. Notably, inhibition of UPF1 and LINC00963 in combination severely impaired the in vivo tumorigenic potential of ECSCs. We demonstrate that the UPF1/LINC00963/miR-508-5p/SOX2 axis has potential value in modulating ECSC maintenance, chemoresistance, and tumorigenesis in EC, which highlights a novel promising target for EC treatment.
Single-cell RNA-sequencing analysis reveals MYH9 promotes renal cell carcinoma development and sunitinib resistance via AKT signaling pathway
Authors: Xu Zhipeng , Liu Min , Wang Jin , Liu Kai , Xu Liuyu , Fan Demin , Zhang Hui , Hu Wenxin , Wei Dan , Wang Jianning 
Published: March 2022

AbstractClear cell renal cell carcinoma (ccRCC) is a serious threat to human health worldwide, while its heterogeneity limits therapeutic success and leads to poor survival outcomes. Single-cell RNA-sequencing (scRNA-seq) is an important technology, which provides deep insights into the genetic characteristics of carcinoma. In this study, we profiled the gene expression of single cells from human ccRCC tissues and adjacent normal tissues using the scRNA-seq. We found that MYH9 was commonly upregulated in the ccRCC cell subgroup. Additionally, MYH9 was of highly expression in ccRCC tissues and predicted poor prognosis of ccRCC patients. MYH9 knockdown in ccRCC cells dampened their proliferative and metastatic potentials, whereas MYH9 overexpression enhanced these properties. In vivo, MYH9 also promoted ccRCC growth. Mechanistic studies showed that MYH9 played these vital roles through AKT signaling pathway. Furthermore, MYH9/AKT axis determined the responses of ccRCC cells to sunitinib treatment and might serve as a biomarker for sunitinib benefits in ccRCC patients. Thus, MYH9 might be a novel therapeutic target and prognostic predictor for ccRCC.
GIT1 protects against breast cancer growth through negative regulation of Notch
Authors: Zhang Songbai , Miyakawa Ayako , Wickström Malin , Dyberg Cecilia , Louhivuori Lauri , Varas-Godoy Manuel , Kemppainen Kati , Kanatani Shigeaki , Kaczynska Dagmara , Ellström Ivar Dehnisch , Elfman Lotta , Kronqvist Pauliina , Repo Heli , Mikoshiba Katsuhiko , Sahlgren Cecilia , Johnsen John Inge , Uhlén Per 
Published: March 2022

AbstractHyperactive Notch signalling is frequently observed in breast cancer and correlates with poor prognosis. However, relatively few mutations in the core Notch signalling pathway have been identified in breast cancer, suggesting that as yet unknown mechanisms increase Notch activity. Here we show that increased expression levels of GIT1 correlate with high relapse-free survival in oestrogen receptor-negative (ER(-)) breast cancer patients and that GIT1 mediates negative regulation of Notch. GIT1 knockdown in ER(-) breast tumour cells increased signalling downstream of Notch and activity of aldehyde dehydrogenase, a predictor of poor clinical outcome. GIT1 interacts with the Notch intracellular domain (ICD) and influences signalling by inhibiting the cytoplasm-to-nucleus transport of the Notch ICD. In xenograft experiments, overexpression of GIT1 in ER(-) cells prevented or reduced Notch-driven tumour formation. These results identify GIT1 as a modulator of Notch signalling and a guardian against breast cancer growth.
Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics
Authors: Leppek Kathrin , Byeon Gun Woo , Kladwang Wipapat , Wayment-Steele Hannah K. , Kerr Craig H. , Xu Adele F. , Kim Do Soon , Topkar Ved V. , Choe Christian , Rothschild Daphna , Tiu Gerald C. , Wellington-Oguri Roger , Fujii Kotaro , Sharma Eesha , Watkins Andrew M. , Nicol John J. , Romano Jonathan , Tunguz Bojan , Diaz Fernando , Cai Hui , Guo Pengbo , Wu Jiewei , Meng Fanyu , Shi Shuai , Participants Eterna , Dormitzer Philip R. , Solórzano Alicia , Barna Maria , Das Rhiju 
Published: March 2022

AbstractTherapeutic mRNAs and vaccines are being developed for a broad range of human diseases, including COVID-19. However, their optimization is hindered by mRNA instability and inefficient protein expression. Here, we describe design principles that overcome these barriers. We develop an RNA sequencing-based platform called PERSIST-seq to systematically delineate in-cell mRNA stability, ribosome load, as well as in-solution stability of a library of diverse mRNAs. We find that, surprisingly, in-cell stability is a greater driver of protein output than high ribosome load. We further introduce a method called In-line-seq, applied to thousands of diverse RNAs, that reveals sequence and structure-based rules for mitigating hydrolytic degradation. Our findings show that highly structured “superfolder” mRNAs can be designed to improve both stability and expression with further enhancement through pseudouridine nucleoside modification. Together, our study demonstrates simultaneous improvement of mRNA stability and protein expression and provides a computational-experimental platform for the enhancement of mRNA medicines.
Amontons-Coulomb-like slip dynamics in acousto-microfluidics
Authors: Quelennec Aurore , Gorman Jason J. , Reyes Darwin R. 
Published: March 2022

AbstractAcousto-microfluidics uses acoustic waves to manipulate and sense particles and fluids, and its integration into biomedical technologies has grown substantially in recent years. Fluid manipulation and measurement with surface acoustic waves rely on the efficient transmission of acoustic energy from the device to the fluid. Acoustic transmission into the fluid can be reduced significantly by slip at the fluid-solid interface, but, up until now, this phenomenon has been widely neglected during the design of acousto-microfluidic devices. Here our interpretation supports that the slip dynamics at the liquid-solid interface in acousto-microfluidics are highly analogous to the Amontons-Coulomb laws for dry friction between solids. In particular, there is a relationship between the local fluid pressure and shear stress, where we show that pressure-shear stress conditions can be divided into slip and no-slip regions, similar to the cone of friction found in dry friction. This improved understanding of slip will enable more reliable and predictable acousto-microfluidic technologies, thus expanding their use in new applications in biology and medicine.
Transcription factors modulate RNA polymerase conformational equilibrium
Authors: Zhu Chengjin , Guo Xieyang , Dumas Philippe , Takacs Maria , Abdelkareem Mo’men , Vanden Broeck Arnaud , Saint-André Charlotte , Papai Gabor , Crucifix Corinne , Ortiz Julio , Weixlbaumer Albert 
Published: March 2022

AbstractRNA polymerase (RNAP) frequently pauses during the transcription of DNA to RNA to regulate gene expression. Transcription factors NusA and NusG modulate pausing, have opposing roles, but can bind RNAP simultaneously. Here we report cryo-EM reconstructions of Escherichia coli RNAP bound to NusG, or NusA, or both. RNAP conformational changes, referred to as swivelling, correlate with transcriptional pausing. NusA facilitates RNAP swivelling to further increase pausing, while NusG counteracts this role. Their structural effects are consistent with biochemical results on two categories of transcriptional pauses. In addition, the structures suggest a cooperative mechanism of NusA and NusG during Rho-mediated transcription termination. Our results provide a structural rationale for the stochastic nature of pausing and termination and how NusA and NusG can modulate it.
Midbrain projection to the basolateral amygdala encodes anxiety-like but not depression-like behaviors
Authors: Morel Carole , Montgomery Sarah E. , Li Long , Durand-de Cuttoli Romain , Teichman Emily M. , Juarez Barbara , Tzavaras Nikos , Ku Stacy M. , Flanigan Meghan E. , Cai Min , Walsh Jessica J. , Russo Scott J. , Nestler Eric J. , Calipari Erin S. , Friedman Allyson K. , Han Ming-Hu 
Published: March 2022

AbstractAnxiety disorders are complex diseases, and often co-occur with depression. It is as yet unclear if a common neural circuit controls anxiety-related behaviors in both anxiety-alone and comorbid conditions. Here, utilizing the chronic social defeat stress (CSDS) paradigm that induces singular or combined anxiety- and depressive-like phenotypes in mice, we show that a ventral tegmental area (VTA) dopamine circuit projecting to the basolateral amygdala (BLA) selectively controls anxiety- but not depression-like behaviors. Using circuit-dissecting ex vivo electrophysiology and in vivo fiber photometry approaches, we establish that expression of anxiety-like, but not depressive-like, phenotypes are negatively correlated with VTA → BLA dopamine neuron activity. Further, our optogenetic studies demonstrate a causal link between such neuronal activity and anxiety-like behaviors. Overall, these data establish a functional role for VTA → BLA dopamine neurons in bi-directionally controlling anxiety-related behaviors not only in anxiety-alone, but also in anxiety-depressive comorbid conditions in mice.
Longitudinal piezoelectric resonant photoelastic modulator for efficient intensity modulation at megahertz frequencies
Authors: Atalar Okan , Van Laer Raphaël , Safavi-Naeini Amir H. , Arbabian Amin 
Published: March 2022

AbstractIntensity modulators are an essential component in optics for controlling free-space beams. Many applications require the intensity of a free-space beam to be modulated at a single frequency, including wide-field lock-in detection for sensitive measurements, mode-locking in lasers, and phase-shift time-of-flight imaging (LiDAR). Here, we report a new type of single frequency intensity modulator that we refer to as a longitudinal piezoelectric resonant photoelastic modulator. The modulator consists of a thin lithium niobate wafer coated with transparent surface electrodes. One of the fundamental acoustic modes of the modulator is excited through the surface electrodes, confining an acoustic standing wave to the electrode region. The modulator is placed between optical polarizers; light propagating through the modulator and polarizers is intensity modulated with a wide acceptance angle and record breaking modulation efficiency in the megahertz frequency regime. As an illustration of the potential of our approach, we show that the proposed modulator can be integrated with a standard image sensor to effectively convert it into a time-of-flight imaging system.
Deep-learning two-photon fiberscopy for video-rate brain imaging in freely-behaving mice
Authors: Guan Honghua , Li Dawei , Park Hyeon-cheol , Li Ang , Yue Yuanlei , Gau Yung-Tian A. , Li Ming-Jun , Bergles Dwight E. , Lu Hui , Li Xingde 
Published: March 2022

AbstractScanning two-photon (2P) fiberscopes (also termed endomicroscopes) have the potential to transform our understanding of how discrete neural activity patterns result in distinct behaviors, as they are capable of high resolution, sub cellular imaging yet small and light enough to allow free movement of mice. However, their acquisition speed is currently suboptimal, due to opto-mechanical size and weight constraints. Here we demonstrate significant advances in 2P fiberscopy that allow high resolution imaging at high speeds (26 fps) in freely-behaving mice. A high-speed scanner and a down-sampling scheme are developed to boost imaging speed, and a deep learning (DL) algorithm is introduced to recover image quality. For the DL algorithm, a two-stage learning transfer strategy is established to generate proper training datasets for enhancing the quality of in vivo images. Implementation enables video-rate imaging at ~26 fps, representing 10-fold improvement in imaging speed over the previous 2P fiberscopy technology while maintaining a high signal-to-noise ratio and imaging resolution. This DL-assisted 2P fiberscope is capable of imaging the arousal-induced activity changes in populations of layer2/3 pyramidal neurons in the primary motor cortex of freely-behaving mice, providing opportunities to define the neural basis of behavior.
Structures of pseudorabies virus capsids
Authors: Wang Guosong , Zha Zhenghui , Huang Pengfei , Sun Hui , Huang Yang , He Maozhou , Chen Tian , Lin Lina , Chen Zhenqin , Kong Zhibo , Que Yuqiong , Li Tingting , Gu Ying , Yu Hai , Zhang Jun , Zheng Qingbing , Chen Yixin , Li Shaowei , Xia Ningshao 
Published: March 2022

AbstractPseudorabies virus (PRV) is a major etiological agent of swine infectious diseases and is responsible for significant economic losses in the swine industry. Recent data points to human viral encephalitis caused by PRV infection, suggesting that PRV may be able to overcome the species barrier to infect humans. To date, there is no available therapeutic for PRV infection. Here, we report the near-atomic structures of the PRV A-capsid and C-capsid, and illustrate the interaction that occurs between these subunits. We show that the C-capsid portal complex is decorated with capsid-associated tegument complexes. The PRV capsid structure is highly reminiscent of other α-herpesviruses, with some additional structural features of β- and γ-herpesviruses. These results illustrate the structure of the PRV capsid and elucidate the underlying assembly mechanism at the molecular level. This knowledge may be useful for the development of oncolytic agents or specific therapeutics against this arm of the herpesvirus family.
SkewDB, a comprehensive database of GC and 10 other skews for over 30,000 chromosomes and plasmids
Authors: Hubert Bert 
Published: March 2022

AbstractGC skew denotes the relative excess of G nucleotides over C nucleotides on the leading versus the lagging replication strand of eubacteria. While the effect is small, typically around 2.5%, it is robust and pervasive. GC skew and the analogous TA skew are a localized deviation from Chargaff’s second parity rule, which states that G and C, and T and A occur with (mostly) equal frequency even within a strand. Different bacterial phyla show different kinds of skew, and differing relations between TA and GC skew. This article introduces an open access database (https://skewdb.org) of GC and 10 other skews for over 30,000 chromosomes and plasmids. Further details like codon bias, strand bias, strand lengths and taxonomic data are also included. The SkewDB can be used to generate or verify hypotheses. Since the origins of both the second parity rule and GC skew itself are not yet satisfactorily explained, such a database may enhance our understanding of prokaryotic DNA.
A point-like thermal light source as a probe for sensing light-matter interaction
Authors: Korn S. , Popp M. A. , Weber H. B. 
Published: March 2022

AbstractHistorically, thermal radiation is related to 3D cavities. In practice, however, it is known that almost any hot surface radiates according to Planck’s law. This approximate universality roots in the smooth electromagnetic mode structure of free space, into which the radiation is emitted. Here, we study the effect for a strongly patterned mode structure and use quasi-transparent point-like thermal light emitters as a probe. As such, we choose current-driven graphene nanojunctions for which the emission into free space obeys Planck’s law. Placed in front of a mirror, however, this process is highly sensitive to a node/antinode pattern of light modes. By varying the distance, we can sample the latter with atomic precision, and observe a deep imprint on the observed spectrum. The experiment allows an unprecedented view on thermal radiation in a spatially/spectrally patterned electromagnetic environment.
A new versatile x–y–z electrospinning equipment for nanofiber synthesis in both far and near field
Authors: Calzado-Delgado Mar , Guerrero-Pérez M. Olga , Yeung King Lun 
Published: March 2022

AbstractThis work describes a versatile electrospinning equipment with rapid, independent, and precise x–y–z movements for large-area depositions of electrospun fibers, direct writing or assembly of fibers into sub-millimeter and micron-sized patterns, and printing of 3D micro- and nanostructures. Its versatility is demonstrated thought the preparation of multilayered functional nanofibers for wound healing, nanofiber mesh for particle filtration, high-aspect ratio printed lines, and freestanding aligned nanofibers.
Decay of homologous chromosome pairs and discovery of males in the thelytokous fungus-growing ant Mycocepurus smithii
Authors: Barros Luísa Antônia Campos , Rabeling Christian , Teixeira Gisele Amaro , dos Santos Ferreira Mariano Cléa , Delabie Jacques Hubert Charles , de Aguiar Hilton Jeferson Alves Cardoso 
Published: March 2022

AbstractThe prevalent mode of reproduction among ants is arrhenotokous parthenogenesis where unfertilized eggs give rise to haploid males and fertilized eggs develop into diploid females. Some ant species are capable of thelytokous parthenogenesis, a type of asexual reproduction where females develop from unfertilized diploid eggs. Thelytoky is well-documented in more than 20 ant species. Cytogenetic data are available for six species demonstrating that some thelytokous ant species are capable of producing males occasionally as well as maintaining their chromosome numbers and proper chromosome pairings. Mycocepurus smithii is a thelytokous fungus-growing ant species that inhabits large parts of Central and South America. Cytogenetic data are unavailable for M. smithii and male individuals were never documented for this species, although the presence of males is expected because genetic recombination was observed in a few sexually reproducing populations in Brazil and haploid sperm was documented from the spermathecae of M. smithii queens. This study aims at comparatively studying asexual and sexual populations of M. smithii using classical and molecular cytogenetic methods to test whether karyotype configuration is modified according to the mode of reproduction in M. smithii. Moreover, we report the discovery of M. smithii males from a sexually reproducing population in the Brazilian state Pará, diagnose the male of M. smithii, and morphologically characterize their spermatozoa. Karyotypic variation was observed within the asexual population (2n = 9, 10, or 11), whereas the chromosome number was fixed in the sexual population (2n = 14, n = 7). Identical karyotypes were maintained within individual M. smithii colonies and karyotype variation was only observed between colonies. In asexual individuals, the karyomorphs showed a decay of homologous chromosome pairs, especially in individuals with the karyomorph 2n = 11, which is potentially caused by relaxed natural selection on proper chromosome pairing. In contrast, females in the sexual population showed proper homologous chromosome pairings. In individuals of both asexual and sexual populations, we find that heterochromatin was localized in centromeric regions and on the short arms of the chromosomes, GC-rich regions were associated with heterochromatic regions, and 18S rDNA genes were located on the largest chromosome pair. This comparative cytogenetic analysis contributes to our understanding about the cytological mechanisms associated with thelytokous parthenogenesis in ants and suggests the decay of chromosome structure in the absence of meiosis and genetic recombination.