bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopamine dysfunction in depression: application of texture analysis to dopamine transporter single-photon emission computed tomography imaging
Authors: Tamura Takehiro , Sugihara Genichi , Okita Kyoji , Mukai Yohei , Matsuda Hiroshi , Shiwaku Hiroki , Takagi Shunsuke , Daisaki Hiromitsu , Tateishi Ukihide , Takahashi Hidehiko 
Published: August 2022

AbstractDopamine dysfunction has been associated with depression. However, results of recent neuroimaging studies on dopamine transporter (DAT), which reflect the function of the dopaminergic system, are inconclusive. The aim of this study was to apply texture analysis, a novel method to extract information about the textural properties of images (e.g., coarseness), to single-photon emission computed tomography (SPECT) imaging in depression. We performed SPECT using123I-ioflupane to measure DAT binding in 150 patients with major depressive disorder (N = 112) and bipolar disorder (N = 38). The texture features of DAT binding in subregions of the striatum were calculated. We evaluated the relationship between the texture feature values (coarseness, contrast, and busyness) and severity of depression, and then examined the effects of medication and diagnosis on such relationship. Furthermore, using the data from 40 healthy subjects, we examined the effects of age and sex on the texture feature values. The degree of busyness of the limbic region in the left striatum linked to the severity of depression (p = 0.0025). The post-hoc analysis revealed that this texture feature value was significantly higher in both the severe and non-severe depression groups than in the remission group (p = 0.001 andp = 0.028, respectively). This finding remained consistent after considering the effect of medication. The effects of age and sex in healthy individuals were not evident in this texture feature value. Our findings imply that the application of texture analysis to DAT-SPECT may provide a state-marker of depression.
Simultaneous augmentation of muscle and bone by locomomimetism through calcium-PGC-1α signaling
Authors: Ono Takehito , Denda Ryosuke , Tsukahara Yuta , Nakamura Takashi , Okamoto Kazuo , Takayanagi Hiroshi , Nakashima Tomoki 
Published: August 2022

AbstractImpaired locomotion has been extensively studied worldwide because those afflicted with it have a potential risk of becoming bedridden. Physical exercise at times can be an effective remedy for frailty, but exercise therapy cannot be applied in all clinical cases. Medication is safer than exercise, but there are no drugs that reinforce both muscle and bone when administered alone. Multiple medications increase the risk of adverse events; thus, there is a need for individual drugs targeting both tissues. To this end, we established a novel sequential drug screening system and identified an aminoindazole derivative, locamidazole (LAMZ), which promotes both myogenesis and osteoblastogenesis while suppressing osteoclastogenesis. Administration of this drug enhanced locomotor function, with muscle and bone significantly strengthened. Mechanistically, LAMZ induced Mef2c and PGC-1α in a calcium signaling–dependent manner. As this signaling is activated upon physical exercise, LAMZ mimics physical exercise. Thus, LAMZ is a promising therapeutic drug for locomotor diseases, including sarcopenia and osteoporosis.
SOX15 transcriptionally increases the function of AOC1 to modulate ferroptosis and progression in prostate cancer
Authors: Ding Yinghui , Feng Yuankang , Huang Zhenlin , Zhang Yu , Li Xiang , Liu Ruoyang , Li Hao , Wang Tao , Ding Yafei , Jia Zhankui , Yang Jinjian 
Published: August 2022

AbstractAmine oxidase copper-containing 1 (AOC1) is considered an oncogene in many types of tumors. Nevertheless, there have been no investigations ofAOC1and its regulatory mechanism in prostate cancer. Here, we reveal a novel action ofAOC1and a tumor suppressor mechanism in prostate cancer.AOC1is downregulated in prostate cancer. Abatement ofAOC1in prostate cancer tissue is positively correlated with the tumor size, lymph node metastasis, and Gleason score for prostate cancer. Conversely, high expression ofAOC1is significantly associated with reduced proliferation and migration in prostate cancer both in vitro and in vivo. We show that the anticancer effect ofAOC1is mediated by its action on spermidine which leads to the activation of reactive oxygen species and ferroptosis.AOC1expression in prostate cancer is positively regulated by the transcription factorSOX15. Therefore,SOX15can transcriptionally promoteAOC1expression and strengthen this effect. TargetingAOC1andSOX15may be promising for the treatment of prostate cancer.
Circular RNA circPOSTN promotes neovascularization by regulating miR-219a-2-3p/STC1 axis and stimulating the secretion of VEGFA in glioblastoma
Authors: Long Niya , Xu Xu , Lin Hongyi , Lv Ying , Zou Shenghui , Cao Han , Chen Xueshu , Zhao Yan , Qi Xiaolan , Yang Hua , Liu Jian , Chu Liangzhao 
Published: August 2022

AbstractGlioblastoma (GBM), the most malignant type of astrocytic tumor, is one of the deadliest cancers prevalent in adults. Along with tumor growth, patients with GBM generally suffer from extensive cerebral edema and apparent symptoms of intracranial hyper-pressure. Accumulating evidence has demonstrated that circRNA plays a critically important role in tumorigenesis and progression. However, the biological function and the underlying mechanism of circRNA in GBM remain elusive. In this study, by conducting gene expression detection based on 15 pairs of GBM clinical specimens and the normal adjunct tissues, we observed that circPOSTN showed abnormally higher expression in GBM. Both loss-of-function and gain-of-function biological experiments demonstrated that circPOSTN scheduled the proliferation, migration, and neovascularization abilities of GBM cells. Further, fluorescence in situ hybridization (FISH) assay, quantitative RT-PCR, and subcellular separation suggested that circPOSTN was predominately localized in the cytoplasm and may serve as a competing endogenous RNA (ceRNA). CircRNA-miRNA interaction prediction based on online analytical processing, AGO2-RIP assay, biotin labeled RNA pulldown assay, and dual-luciferase reporter assay revealed that circPOSTN sponged miR-219a-2-3p, limited its biological function, and ultimately upregulated their common downstream gene STC1. Finally, by carrying out in vitro and in vivo functional assays, we uncovered a new regulatory axis circPOSTN/miR-219a-2-3p/STC1 that promoted GBM neovascularization by increasing vascular endothelial growth factor A (VEGFA) secretion. Our study underscores the critical role of circPOSTN in GBM progression, providing a novel insight into GBM anti-tumor therapy.
The mitochondrial RNA polymerase POLRMT promotes skin squamous cell carcinoma cell growth
Authors: Wang Yulong , Ou Li , Li Xirong , Zheng Tingyu , Zhu Wei-pei , Li Ping , Wu Lijun , Zhao Tianlan 
Published: August 2022

AbstractRNA polymerase mitochondrial (POLRMT) expression and the potential biological functions in skin squamous cell carcinoma (SCC) were explored. We showed that POLRMT is significantly elevated in skin SCC. Genetic depletion of POLRMT, using shRNA-induced knockdown or CRISPR/Cas9-mediated knockout (KO), resulted in profound anti-skin SCC cell activity. In patient-derived primary skin SCC cells or immortalized lines (A431 and SCC-9), POLRMT shRNA or KO potently suppressed mitochondrial DNA (mtDNA) transcription and suppressed cell viability, proliferation and migration. POLRMT shRNA or KO impaired mitochondrial functions in different skin SCC cells, leading to production of ROS (reactive oxygen species), depolarization of mitochondria and depletion of ATP. Moreover, mitochondrial apoptosis cascade was induced in POLRMT-depleted skin SCC cells. IMT1, a POLRMT inhibitor, largely inhibited proliferation and migration, while inducing depolarization of mitochondria and apoptosis in primary skin SCC cells. Contrarily, ectopic overexpression of POLRMT increased mtDNA transcription and augmented skin SCC cell growth. Importantly, POLRMT shRNA adeno-associated virus injection robustly hindered growth of the subcutaneous A431 xenografts in mice. In the POLRMT shRNA virus-treated A431 xenograft tissues, POLRMT depletion, mtDNA transcription inhibition, cell apoptosis, lipid peroxidation and ATP depletion were detected. Together, overexpressed POLRMT increases mtDNA transcription and promotes skin SCC growth.
Pan-African genome demonstrates how population-specific genome graphs improve high-throughput sequencing data analysis
Authors: Tetikol H. Serhat , Turgut Deniz , Narci Kubra , Budak Gungor , Kalay Ozem , Arslan Elif , Demirkaya-Budak Sinem , Dolgoborodov Alexey , Kabakci-Zorlu Duygu , Semenyuk Vladimir , Jain Amit , Davis-Dusenbery Brandi N. 
Published: August 2022

AbstractGraph-based genome reference representations have seen significant development, motivated by the inadequacy of the current human genome reference to represent the diverse genetic information from different human populations and its inability to maintain the same level of accuracy for non-European ancestries. While there have been many efforts to develop computationally efficient graph-based toolkits for NGS read alignment and variant calling, methods to curate genomic variants and subsequently construct genome graphs remain an understudied problem that inevitably determines the effectiveness of the overall bioinformatics pipeline. In this study, we discuss obstacles encountered during graph construction and propose methods for sample selection based on population diversity, graph augmentation with structural variants and resolution of graph reference ambiguity caused by information overload. Moreover, we present the case for iteratively augmenting tailored genome graphs for targeted populations and demonstrate this approach on the whole-genome samples of African ancestry. Our results show that population-specific graphs, as more representative alternatives to linear or generic graph references, can achieve significantly lower read mapping errors and enhanced variant calling sensitivity, in addition to providing the improvements of joint variant calling without the need of computationally intensive post-processing steps.
Fate mapping of hematopoietic stem cells reveals two pathways of native thrombopoiesis
Authors: Morcos Mina N. F. , Li Congxin , Munz Clara M. , Greco Alessandro , Dressel Nicole , Reinhardt Susanne , Sameith Katrin , Dahl Andreas , Becker Nils B. , Roers Axel , Höfer Thomas , Gerbaulet Alexander 
Published: August 2022

AbstractHematopoietic stem cells (HSCs) produce highly diverse cell lineages. Here, we chart native lineage pathways emanating from HSCs and define their physiological regulation by computationally integrating experimental approaches for fate mapping, mitotic tracking, and single-cell RNA sequencing. We find that lineages begin to split when cells leave the tip HSC population, marked by high Sca-1 and CD201 expression. Downstream, HSCs either retain high Sca-1 expression and the ability to generate lymphocytes, or irreversibly reduce Sca-1 level and enter into erythro-myelopoiesis or thrombopoiesis. Thrombopoiesis is the sum of two pathways that make comparable contributions in steady state, a long route via multipotent progenitors and CD48hi megakaryocyte progenitors (MkPs), and a short route from HSCs to developmentally distinct CD48−/lo MkPs. Enhanced thrombopoietin signaling differentially accelerates the short pathway, enabling a rapid response to increasing demand. In sum, we provide a blueprint for mapping physiological differentiation fluxes from HSCs and decipher two functionally distinct pathways of native thrombopoiesis.
Value-free random exploration is linked to impulsivity
Authors: Dubois Magda , Hauser Tobias U. 
Published: August 2022

AbstractDeciding whether to forgo a good choice in favour of exploring a potentially more rewarding alternative is one of the most challenging arbitrations both in human reasoning and in artificial intelligence. Humans show substantial variability in their exploration, and theoretical (but only limited empirical) work has suggested that excessive exploration is a critical mechanism underlying the psychiatric dimension of impulsivity. In this registered report, we put these theories to test using large online samples, dimensional analyses, and computational modelling. Capitalising on recent advances in disentangling distinct human exploration strategies, we not only demonstrate that impulsivity is associated with a specific form of exploration—value-free random exploration—but also explore links between exploration and other psychiatric dimensions.
Histone H3K36me2 and H3K36me3 form a chromatin platform essential for DNMT3A-dependent DNA methylation in mouse oocytes
Authors: Yano Seiichi , Ishiuchi Takashi , Abe Shusaku , Namekawa Satoshi H. , Huang Gang , Ogawa Yoshihiro , Sasaki Hiroyuki 
Published: August 2022

AbstractEstablishment of the DNA methylation landscape of mammalian oocytes, mediated by the DNMT3A-DNMT3L complex, is crucial for reproduction and development. In mouse oocytes, high levels of DNA methylation occur exclusively in the transcriptionally active regions, with moderate to low levels of methylation in other regions. Histone H3K36me3 mediates the high levels of methylation in the transcribed regions; however, it is unknown which histone mark guides the methylation in the other regions. Here, we show that, in mouse oocytes, H3K36me2 is highly enriched in the X chromosome and is broadly distributed across all autosomes. Upon H3K36me2 depletion, DNA methylation in moderately methylated regions is selectively affected, and a methylation pattern unique to the X chromosome is switched to an autosome-like pattern. Furthermore, we find that simultaneous depletion of H3K36me2 and H3K36me3 results in global hypomethylation, comparable to that of DNMT3A depletion. Therefore, the two histone marks jointly provide the chromatin platform essential for guiding DNMT3A-dependent DNA methylation in mouse oocytes.
The spatio-temporal evolution of multiple myeloma from baseline to relapse-refractory states
Authors: Rasche Leo , Schinke Carolina , Maura Francesco , Bauer Michael A. , Ashby Cody , Deshpande Shayu , Poos Alexandra M. , Zangari Maurizio , Thanendrarajan Sharmilan , Davies Faith E. , Walker Brian A. , Barlogie Bart , Landgren Ola , Morgan Gareth J. , van Rhee Frits , Weinhold Niels 
Published: August 2022

AbstractDeciphering Multiple Myeloma evolution in the whole bone marrow is key to inform curative strategies. Here, we perform spatial-longitudinal whole-exome sequencing, including 140 samples collected from 24 Multiple Myeloma patients during up to 14 years. Applying imaging-guided sampling we observe three evolutionary patterns, including relapse driven by a single-cell expansion, competing/co-existing sub-clones, and unique sub-clones at distinct locations. While we do not find the unique relapse sub-clone in the baseline focal lesion(s), we show a close phylogenetic relationship between baseline focal lesions and relapse disease, highlighting focal lesions as hotspots of tumor evolution. In patients with ≥3 focal lesions on positron-emission-tomography at diagnosis, relapse is driven by multiple distinct sub-clones, whereas in other patients, a single-cell expansion is typically seen (p < 0.01). Notably, we observe resistant sub-clones that can be hidden over years, suggesting that a prerequisite for curative therapies would be to overcome not only tumor heterogeneity but also dormancy.
Three types of genes underlying the Gametophyte factor1 locus cause unilateral cross incompatibility in maize
Authors: Wang Yuebin , Li Wenqiang , Wang Luxi , Yan Jiali , Lu Gang , Yang Ning , Xu Jieting , Wang Yuqing , Gui Songtao , Chen Gengshen , Li Shuyan , Wu Chengxiu , Guo Tingting , Xiao Yingjie , Warburton Marilyn L. , Fernie Alisdair R. , Dresselhaus Thomas , Yan Jianbing 
Published: August 2022

AbstractUnilateral cross incompatibility (UCI) occurs between popcorn and dent corn, and represents a critical step towards speciation. It has been reported thatZmGa1P, encoding a pectin methylesterase (PME), is a male determinant of theGa1locus. However, the female determinant and the genetic relationship between male and female determinants at this locus are unclear. Here, we report three different types, a total of seven linked genes underlying theGa1locus, which control UCI phenotype by independently affecting pollen tube growth in both antagonistic and synergistic manners. These include five pollen-expressedPMEgenes (ZmGa1Ps-m), a silk-expressed PME gene (ZmPME3), and another silk-expressed gene (ZmPRP3), encoding a pathogenesis-related (PR) proteins.ZmGa1Ps-mconfer pollen compatibility. Presence ofZmPME3causes silk to reject incompatible pollen.ZmPRP3promotes incompatibility pollen tube growth and thereby breaks the blocking effect ofZmPME3. In addition, evolutionary genomics analyses suggest that the divergence of theGa1locus existed before maize domestication and continued during breeding improvement. The knowledge gained here deepen our understanding of the complex regulation of cross incompatibility.
Revealing the role of liquid preordering in crystallisation of supercooled liquids
Authors: Hu Yuan-Chao , Tanaka Hajime 
Published: August 2022

AbstractThe recent discovery of non-classical crystal nucleation pathways has revealed the role of fluctuations in the liquid structural order, not considered in classical nucleation theory. On the other hand, classical crystal growth theory states that crystal growth is independent of interfacial energy, but this is questionable. Here we elucidate the role of liquid structural ordering in crystal nucleation and growth using computer simulations of supercooled liquids. We find that suppressing the crystal-like structural order in the supercooled liquid through a new order-killing strategy can reduce the crystallisation rate by several orders of magnitude. This indicates that crystal-like liquid preordering and the associated interfacial energy reduction play an essential role in nucleation and growth processes, forcing critical modifications of the classical crystal growth theory. Furthermore, we evaluate the importance of this additional factor for different types of liquids. These findings shed new light on the fundamental understanding of crystal growth kinetics.
Maturation and substrate processing topography of the Plasmodium falciparum invasion/egress protease plasmepsin X
Authors: Mukherjee Sumit , Nguyen Suong , Sharma Eashan , Goldberg Daniel E. 
Published: August 2022

AbstractThe malaria parasite Plasmodium invades a host erythrocyte, multiplies within a parasitophorous vacuole (PV) and then ruptures the PV and erythrocyte membranes in a process known as egress. Both egress and invasion are controlled by effector proteins discharged from specialized secretory organelles. The aspartic protease plasmepsin X (PM X) regulates activity for many of these effectors, but it is unclear how PM X accesses its diverse substrates that reside in different organelles. PM X also autoprocesses to generate different isoforms. The function of this processing is not understood. We have mapped the self-cleavage sites and have constructed parasites with cleavage site mutations. Surprisingly, a quadruple mutant that remains full-length retains in vitro activity, is trafficked normally, and supports normal egress, invasion and parasite growth. The N-terminal half of the prodomain stays bound to the catalytic domain even after processing and is required for proper intracellular trafficking of PM X. We find that this enzyme cleaves microneme and exoneme substrates before discharge, while the rhoptry substrates that are dependent on PM X activity are cleaved after exoneme discharge into the PV. The data give insight into the temporal, spatial and biochemical control of this unusual but important aspartic protease.
Generative design of stable semiconductor materials using deep learning and density functional theory
Authors: Siriwardane Edirisuriya M. Dilanga , Zhao Yong , Perera Indika , Hu Jianjun 
Published: August 2022

AbstractSemiconductor device technology has greatly developed in complexity since discovering the bipolar transistor. In this work, we developed a computational pipeline to discover stable semiconductors by combining generative adversarial networks (GAN), classifiers, and high-throughput first-principles calculations. We used CubicGAN, a GAN-based algorithm for generating cubic materials and developed a classifier to screen the semiconductors and studied their stability using first principles. We found 12 stable AA$${}^{\prime}$$′MH6semiconductors in the F-43m space group including BaNaRhH6, BaSrZnH6, BaCsAlH6, SrTlIrH6, KNaNiH6, NaYRuH6, CsKSiH6, CaScMnH6, YZnMnH6, NaZrMnH6, AgZrMnH6, and ScZnMnH6. Previous research reported that five AA$${}^{\prime}$$′IrH6 semiconductors with the same space group were synthesized. Our research shows that AA$${}^{\prime}$$′MnH6and NaYRuH6semiconductors have considerably different properties compared to the rest of the AA$${}^{\prime}$$′MH6semiconductors. Based on the accurate hybrid functional calculations, AA$${}^{\prime}$$′MH6semiconductors are found to be wide-bandgap semiconductors. Moreover, BaSrZnH6and KNaNiH6are direct-bandgap semiconductors, whereas others exhibit indirect bandgaps.
Sunlit zebra stripes may confuse the thermal perception of blood vessels causing the visual unattractiveness of zebras to horseflies
Authors: Takács Péter , Száz Dénes , Vincze Miklós , Slíz-Balogh Judit , Horváth Gábor 
Published: August 2022

AbstractMultiple hypotheses have been proposed for possible functions of zebra stripes. The most thoroughly experimentally supported advantage of zebra stripes is their visual unattractiveness to horseflies (tabanids) and tsetse flies. We propose here a plausible hypothesis why biting horseflies avoid host animals with striped pelages: in sunshine the temperature gradients of the skin above the slightly warmer blood vessels are difficult to distinguish from the temperature gradients induced by the hairs at the borderlines of warmer black and cooler white stripes. To test this hypothesis, we performed a field experiment with tabanids walking on a host-imitating grey test target with vessel-mimicking thin black stripes which were slightly warmer than their grey surroundings in sunshine, while under shady conditions both areas had practically the same temperature as demonstrated by thermography. We found that horseflies spend more time walking on thin black stripes than surrounding grey areas as expected by chance, but only when the substrate is sunlit. This is because the black stripes are warmer than the surrounding grey areas in the sun, but not in the shade. This is consistent with the flies’ well-documented attraction to warmer temperatures and provides indirect support for the proposed hypothesis. The frequent false vessel locations at the numerous black–white borderlines, the subsequent painful bitings with unsuccessful blood-sucking attempts and the host’s fly-repellent reactions enhance considerably the chance that horseflies cannot evade host responses and are swatted by them. To eliminate this risk, a good evolutionary strategy was the avoidance of striped (and spotted) host animals.