bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for a Relatively Warm Mid‐to Late Holocene on the Southeastern Tibetan Plateau
Authors: Feng Xiaoping , Zhao Cheng , D'Andrea William J. , Hou Juzhi , Yang Xiangdong , Xiao Xiayun , Shen Ji , Duan Yanwu , Chen Fahu
Published: August 2022

The Holocene temperature discrepancy between paleoclimate reconstructions and climate model simulations—known as the Holocene temperature conundrum—calls for new high‐quality Holocene temperature records at high elevations. Here, we present a quantitative Holocene mean annual air temperature record based on a site‐specific branched glycerol dialkyl glycerol tetraethers calibration from a small remote alpine lake on the southeastern Tibetan Plateau. The record reveals a temperature history comprising a relatively cool early Holocene (before 7 ka) followed by a warmer mid‐ to late‐Holocene (after 7 ka), which was likely linked to increasing local annual insolation and greenhouse gases. Three cold events punctuated the general warming trend ca. 10.4 ka, 3.7 ka, and 1.7 ka BP, and correspond closely in time to ice rafting events in the North Atlantic, and to episodes of volcanism and/or unusual solar activity. The entire Holocene temperatures are cooler than the previously identified anthropogenic warming from 1990–2015 AD.
Enhanced Weathering Triggered the Transient Oxygenation Event at ∼1.57 Ga
Authors: Tang Dongjie , Fu Xuewu , Shi Xiaoying , Zhou Limin , Zheng Wang , Li Chao , Xu Dongtao , Zhou Xiqiang , Xie Baozeng , Zhu Xiyan , Jiang Ganqing
Published: August 2022

The mid‐Proterozoic (∼1.8–0.8 Ga) is characterized by low atmospheric oxygen and pervasive oceanic anoxia, with transient oxygenation events. One of the oxygenation events happened at ∼1.57 Ga, during which atmospheric O2 may have reached ≥4% present atmospheric level (PAL) and thus promoted the evolution of multi‐cellular eukaryotes. The cause of this oxygenation event, however, remained unknown. Here, we report δ202Hg, ∆199Hg, P concentration, Rb/Al, and εNd(t) data across the ∼1.57 Ga oxygenation event in the Gaoyuzhuang Formation of North China. The positive δ202Hg, εNd(t), and negative Δ199Hg shifts, plus the accompanied peaks in Rb/Al, P, and I/(Ca + Mg), suggest that this oxygenation event was likely resulted from enhanced weathering of intermediate to mafic rocks, which may have promoted primary production via increasing P influx to the ocean and led to the rise in oxygen levels. The data indicate that enhanced weathering input could trigger transient oxygenation events during the mid‐Proterozoic.
Bores Observed During the Warm Season of 2015–2019 Over the Southern North China Plain
Authors: Zhang Shushi , Parsons David B. , Xu Xin , Sun Jisong , Wu Tianjie , Xu Fen , Wei Na , Chen Gang
Published: August 2022

This first multi‐year investigation focuses on bores over the southern North China Plain during the 2015–2019 warm seasons. Bore structure depended on location with undular bores tending to occur close to the coast and non‐undular bores to the west near elevated terrain. Bores were most likely to occur during June and July when convection is active. While bore frequency over the Southern Great Plains (SGP) of U.S. is linked to the region's nocturnal low‐level jet, the bores herein were sensitive to the synoptic regime with ∼80% occurring during 4‐to‐5‐day periods under three different synoptic regimes. The bores had shorter durations than their SGP counterparts and a far wider range in their direction of propagation. Overall, these findings find regional differences in bores' frequency, movement, and structure serving an impetus for future investigations of nocturnal mesoscale convective systems and bores over China and other locations worldwide.
A Geo‐Structurally Based Correction Factor for Apparent Dissolution Rates in Fractured Media
Authors: Hyman Jeffrey D. , Navarre‐Sitchler Alexis , Andrews Elizabeth , Sweeney Matthew R. , Karra Satish , Carey J. William , Viswanathan Hari S.
Published: August 2022

Field measurements of apparent geochemical weathering reaction rates in subsurface fractured porous media are known to deviate from laboratory measurements by multiple orders of magnitude. To date, there is no geologically based explanation for this discrepancy that can be used to predict reaction rates in field systems. Proposed correction factors are typically based on ad hoc characterizations related to geochemical kinetic models. Through a series of high‐fidelity reactive transport simulations of mineral dissolution within explicit 3D discrete fracture networks, we are able to link the geo‐structural attributes with reactive transport observations. We develop a correction factor to linear transition state theory for the prediction of the apparent dissolution rate based on measurable geological properties. The modified rate law shows excellent agreement with numerical simulations, indicating that geological structure could be a primary reason for the discrepancy between laboratory and field observations of apparent dissolution rates in fractured media.
Effect of ICME‐Driven Storms on Field‐Aligned and Ionospheric Currents From AMPERE and SuperMAG
Authors: Pedersen M. N. , Vanhamäki H. , Aikio A. T. , Waters C. L. , Gjerloev J. W. , Käki S. , Workayehu A. B.
Published: August 2022

This study investigates the field‐aligned currents (FACs) and ionospheric equivalent currents for interplanetary coronal mass ejection (ICME)‐driven storms by considering 45 events with a minimum Dst ≤ −50 nT. The FACs and ionospheric equivalent currents are studied by applying a superposed epoch analysis to data from AMPERE and SuperMAG with the zero epoch (t0) centered at the onset of the storm main phase. The currents and number of substorm onsets begin to increase 3 hr before t0 and maximizes about 1 hr after t0. The currents and number of substorm onsets remain high throughout the entire storm main phase, until at t0 + 14 hr they start to slowly relax back to quiet time conditions. The storms were separated into two groups based on the solar wind dynamic pressure pdyn around t0. High pdyn storms are mostly driven by the sheath region ahead of the ejecta. These storms have short main phase durations and larger currents early in the main phase which maximize at t0 + 50 min. The low pdyn group contains storms that start during the magnetic clouds (MC) and have gradually increasing currents that maximize at t0 + 11 hr, close to the end of the storm main phase. For the first 4 hr of the storm main phase, the currents in sheath‐driven storms are larger than for MC‐driven storms. The Russell‐McPherron effect is less important for ICME‐driven storms where only 44% have a contribution, compared to 82% of high speed stream/stream interaction driven storms.
The Role of Crustal Accretion Variations in Determining Slab Hydration at an Atlantic Subduction Zone
Authors: Allen R. W. , Collier J. S. , Henstock T. J. ,   The VoiLA Consortium
Published: August 2022

We present a 2D P‐wave velocity model from the outer rise region of the Lesser Antilles island arc, the first wide‐angle seismic study of outer rise processes at an Atlantic subduction zone. The survey consists of 46 OBS receivers over a 174 km profile with velocities resolved to 15 km below top basement. The final velocity model, produced through tomographic inversion, shows a clear decrease in the velocity of the lower crust and upper mantle of the incoming plate as it approaches the trench. We attribute this drop to outer rise bend‐related hydration, similar to Pacific cases, but superimposed on spatial variations in hydration generated at the slow‐spreading ridge axis. In thin, tectonically controlled crust formed under magma‐poor spreading conditions the superposition of these sources of hydration results in compressional velocities as low as 6.5 km s−1 beneath the PmP reflector. In contrast, segments of crust interpreted as having formed under magma‐rich conditions show velocity reductions and inferred hydrous alteration more like that observed in the Pacific. Hence, variations in the style of crustal accretion, which is observed on 50–100 km length scales both along and across isochrons, is a primary control over the distribution of water within the slab at Atlantic subduction systems. This heterogeneous pattern of water storage within the slab is likely further complicated by along strike variations in outer rise bending, subducting fracture zones and deformation at segment ends and may have important implications for our understanding of long‐term patterns of hazard at Atlantic subduction systems.
A Depth‐Transect of Ocean Deoxygenation During the Paleocene‐Eocene Thermal Maximum: Magnetofossils in Sediment Cores From the Southeast Atlantic
Authors: Xue Pengfei , Chang Liao , Dickens Gerald R. , Thomas Ellen
Published: August 2022

The Paleocene‐Eocene Thermal Maximum (PETM, ∼56 Ma) presents a past analog for future global warming. Previous studies provided evidence for major loss of dissolved oxygen during the PETM, although understanding the degree and distribution of oxygen loss poses challenges. Magnetofossils produced by magnetotactic bacteria are sensitive to redox conditions in sediments and water columns, and have been used to reconstruct paleoredox conditions over a range of geological settings. Here, we present records of well‐preserved magnetofossils from cores along Walvis Ridge in the Southeast Atlantic that span the PETM across a depth transect (∼1,500–3,600 m paleodepth). Hysteresis, isothermal remanent magnetization curves, first‐order reversal curve diagrams, and low‐temperature magnetic measurements document large variations in magnetic properties of magnetofossils, which relate to time and water depth. Abundant magnetofossil grains are present within the studied sediments, and their morphologies change with paleodepth, as shown by transmission electron microscope observations. Magnetofossils from samples within the PETM onset at the deeper sites (∼2,600–3,600 m paleodepth) have lower coercivity values, a higher oxidation degree, and smaller grain sizes than those from shallower sites (∼1,500–1,800 m paleodepth), likely reflecting changes in paleoredox conditions at different paleodepths. We use the magnetofossil records to reconstruct relative changes in dissolved oxygen content at different water depths through the PETM, and suggest that ocean deoxygenation likely expanded downwards in the early stages of the PETM. We thus demonstrate the value of magnetofossil records for paleoenvironmental reconstructions over time and space, particularly for sediments that lack carbonate fossils.
The Changing Behavior of the West Greenland Current System in a Very High‐Resolution Model
Authors: Gou Ruijian , Pennelly Clark , Myers Paul G.
Published: August 2022

Analyzing a high‐resolution (1/60°) numerical model over 2008–2018, the inter‐annual variability of the West Greenland Coastal Current (WGCC) on the shelf and West Greenland Current (WGC) at the shelf break is presented. Both currents flow from Cape Farewell and extend to Davis Strait, with their speeds and transports corresponding well with observations. The trend over the study period of the WGCC and WGC strength near southwest Greenland are opposite, with the former declining while the latter strengthened, both by a speed change above 0.1 m/s. Both currents are predominantly buoyancy forced, but wind forcing becomes more dominant approaching Davis Strait. The main exchanges from the two currents with the interior of the Labrador Sea occur between Cape Desolation and Fylla Bank. The net volume, freshwater, heat transport decreases between these two sections are 1.4 Sv, 13 mSv, 36.7 TW, respectively. The freshwater transport of the WGC itself does not drop in between these sections, receiving freshwater from the WGCC to compensate for the losses to the basin interior. Thus, we see significant freshwater (83.1 mSv) and heat transports (70.7 TW) of the WGC remaining at Fylla Bank that reach the northern basin instead of being fluxed into the interior of the Labrador Sea. This suggests that the exchange between the boundary current system and the interior is more limited than previously thought, and most of the Greenland and Arctic melt reaches the northern Labrador Sea. Our results highlight the importance of resolving the WGCC and shelf processes.
The Role of Fronts in Horizontal Transports of the Changjiang River Plume in Summer and the Implications for Phytoplankton Blooms
Authors: Li Shuangzhao , Zhang Zhaoru , Zhou Meng , Wang Chuning , Wu Hui , Zhong Yisen
Published: August 2022

Frontal processes play a significant role in estuarine and coastal ecosystem dynamics. In this study, a hydrodynamic model of the Changjiang River plume was developed based on the Regional Ocean Modeling System, and Lagrangian Coherent Structures (LCSs) were applied to the model simulations to analyze the horizontal transport characteristics of the river plume with the surface plume front, the tidal front, and the far‐field plume front in summer. The results show that the plume currents during the ebb tide were supercritical upstream of the near‐field surface plume front and tidal front and subcritical downstream of the fronts. In the LCSs results, transport barriers existing in the frontal regions indicated that the materials hardly crossed the fronts and tended to accumulate. The water parcels near the surface plume front and the tidal front in the near‐field entirely originated from the Changjiang River Estuary. The surface East China Sea shelf water could not influence the near‐field region due to the transport barrier formed by the far‐field plume front. Momentum balance analysis results reveal that the plume currents were in geostrophic balance around the near‐field fronts, rendering the flows mainly in the along‐front direction and significantly weakening the cross‐shore flows. These physical processes provided enough residence time of the plume water and growth time for phytoplankton in the frontal region and thus favored algal blooming with sufficient nutrients. Even though the frontal convergence induced by transport barriers also appeared near the far‐field plume front, insufficient supply of nutrients limited the phytoplankton growth.
Puy de Dôme Station (France): A Stoichiometric Approach to Compound Classification in Clouds
Authors: Renard Pascal , Bianco Angelica , Jänis Janne , Kekäläinen Timo , Bridoux Maxime , Deguillaume Laurent
Published: August 2022

Seven cloud water samples were collected from May to October 2018 at the Puy de Dôme station (PUY) in France and analyzed by positive‐ion atmospheric pressure photoionization [(+)APPI] Fourier transform ion cyclotron resonance mass spectrometry. The assigned formulas (ranging from 3,865 to 6,380) were attributed using the multidimensional stoichiometric constraint classification of Rivas‐Ubach et al. (2018, https://doi.org.10.1021/acs.analchem.8b00529) to six main categories (RUCs): LipidC, ProteinC, Amino‐sugarC, CarbohydrateC, NucleotideC, and OxyaromaticC. Back trajectories were calculated by the computing atmospheric trajectory tool (CAT) model to obtain information on the air mass history. Partial least square regressions were performed using chemical data, CAT back‐trajectory calculations and FT‐ICR MS data to analyze the environmental variability of the organic sample composition. ProteinC is correlated with the continental surface for air masses transported within the boundary layer, and Amino‐sugarC is strongly correlated with acetate, NO3− and NH4+, suggesting Anthropogenic sources for amino sugars and proteins. LipidC is correlated with the sea surface for air masses transported within the free troposphere, confirming the long‐range transport of marine biogenic sources. Concerning Oxy‐aromaticC, given the correlations with oxidants and pollutants, as well as anti‐correlations with local influence, we proposed a mechanism of oxidation from remote anthropogenic sources.
Multifunctional resonant wavefront-shaping meta-optics based on multilayer and multi-perturbation nonlocal metasurfaces
Authors: Malek Stephanie C. , Overvig Adam C. , Alù Andrea , Yu Nanfang
Published: August 2022

Photonic devices rarely provide both elaborate spatial control and sharp spectral control over an incoming wavefront. In optical metasurfaces, for example, the localized modes of individual meta-units govern the wavefront shape over a broad bandwidth, while nonlocal lattice modes extended over many unit cells support high quality-factor resonances. Here, we experimentally demonstrate nonlocal dielectric metasurfaces in the near-infrared that offer both spatial and spectral control of light, realizing metalenses focusing light exclusively over a narrowband resonance while leaving off-resonant frequencies unaffected. Our devices attain this functionality by supporting a quasi-bound state in the continuum encoded with a spatially varying geometric phase. We leverage this capability to experimentally realize a versatile platform for multispectral wavefront shaping where a stack of metasurfaces, each supporting multiple independently controlled quasi-bound states in the continuum, molds the optical wavefront distinctively at multiple wavelengths and yet stay transparent over the rest of the spectrum. Such a platform is scalable to the visible for applications in augmented reality and transparent displays.
ZNF655 accelerates progression of pancreatic cancer by promoting the binding of E2F1 and CDK1
Authors: Shao Zhuo , Li Chenggang , Wu Qiao , Zhang Xingmao , Dai Yang , Li Shenming , Liu Xinyuan , Zheng Xinying , Zhang Jiansheng , Fan Hua
Published: August 2022

Pancreatic cancer has an extremely terrible prognosis and is a common cause of cancer death. In this study, the clinic value, biological function and underlying mechanisms of Zinc finger protein 655 (ZNF655) in human pancreatic cancer were evaluated. The expression level of ZNF655 in pancreatic cancer was determined by immunohistochemistry (IHC) staining. The biological effects of ZNF655 in pancreatic cancer cells was investigated by loss/gain-of-function assays in vitro and in vivo. The downstream molecular mechanism of ZNF655 was explored using co-immunoprecipitation (Co-IP), dual-luciferase reporter and chromatin immunoprecipitation (Ch-IP). ZNF655 expression was significantly elevated in human pancreatic cancer and possessed clinical value in predicting poor prognosis. Functionally, ZNF655 knockdown inhibited the biological progression of pancreatic cancer cells, which was characterized by weaken proliferation, enhanced apoptosis, arrested cell cycle in G2, impeded migration, and suppressed tumor growth. Mechanistically, ZNF655 played an important role in promoting the binding of E2F transcription factor 1 (E2F1) to the cyclin-dependent kinase 1 (CDK1) promoter. Furthermore, knockdown of CDK1 alleviated the promoting effects of ZNF655 overexpression in pancreatic cancer cells. The promotive role of ZNF655 in pancreatic cancer via CDK1 was determined, which drew further interest regarding its clinical application as a promising therapeutic target.
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

Dopamine 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

Impaired 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

Amine 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

Glioblastoma (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

RNA 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

Graph-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

Hematopoietic 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

Deciding 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

Establishment 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

Deciphering 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

Unilateral 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

The 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

The 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

Semiconductor 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

Multiple 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.
Dufour effect on unsteady MHD flow past a vertical plate embedded in porous medium with ramped temperature
Authors: Sarma Subhrajit , Ahmed Nazibuddin
Published: August 2022

The present investigation aims to find an exact solution to the problem of a free convective, viscous, radiating, chemically reacting, optically thick, non-gray, and incompressible MHD flow past an exponentially accelerated semi-infinite vertical plate in presence of a transverse magnetic field. The medium of flow is porous. Arbitrary ramped temperature and diffusion thermo effects are also considered. Rosseland approximation method is used to describe the flux that appears in the energy equation. The effects of different parameters on flow and transport characteristics are discussed with the help of suitable graphs. It is noticed that velocity field and concentration field decreases but temperature field increases with an upsurge in Schmidt number. Also, Nusselt number and skin friction rise with increasing chemical reaction parameter but lowers with increasing radiation parameter. Faster consumption of chemical substances decelerates both concentration and velocity but accelerates temperature of the fluid. An interesting outcome outcome of our investigation is that both Dufour effect and arbitrary ramped temperature diminishes fluid velocity.
Identifying neurocognitive disorder using vector representation of free conversation
Authors: Horigome Toshiro , Hino Kimihiro , Toyoshiba Hiroyoshi , Shindo Norihisa , Funaki Kei , Eguchi Yoko , Kitazawa Momoko , Fujita Takanori , Mimura Masaru , Kishimoto Taishiro
Published: August 2022

In recent years, studies on the use of natural language processing (NLP) approaches to identify dementia have been reported. Most of these studies used picture description tasks or other similar tasks to encourage spontaneous speech, but the use of free conversation without requiring a task might be easier to perform in a clinical setting. Moreover, free conversation is unlikely to induce a learning effect. Therefore, the purpose of this study was to develop a machine learning model to discriminate subjects with and without dementia by extracting features from unstructured free conversation data using NLP. We recruited patients who visited a specialized outpatient clinic for dementia and healthy volunteers. Participants’ conversation was transcribed and the text data was decomposed from natural sentences into morphemes by performing a morphological analysis using NLP, and then converted into real-valued vectors that were used as features for machine learning. A total of 432 datasets were used, and the resulting machine learning model classified the data for dementia and non-dementia subjects with an accuracy of 0.900, sensitivity of 0.881, and a specificity of 0.916. Using sentence vector information, it was possible to develop a machine-learning algorithm capable of discriminating dementia from non-dementia subjects with a high accuracy based on free conversation.
Exploring how plasma- and muscle-related parameters affect trout hemolysis as a route to prevent hemoglobin-mediated lipid oxidation of fish muscle
Authors: Ghirmai Semhar , Wu Haizhou , Axelsson Michael , Matsuhira Takashi , Sakai Hiromi , Undeland Ingrid
Published: August 2022

Hemoglobin (Hb) is a powerful promoter of lipid oxidation, particularly in muscle of small pelagic fish species and fish by-products, both having high Hb-levels and highly unsaturated lipids. As Hb is located within the red blood cells (RBCs) it is here hypothesized that the perishable polyunsaturated fatty acids (PUFAs) can be protected from oxidation by limiting hemolysis during early fish processing. Using a model system consisting of washed-resuspended trout (Oncorhynchus mykiss) RBCs (wr-RBCs), the aim of this study was to evaluate how RBC lysis under cold storage was affected by selected parameters linked to blood or muscle: bacterial growth, energy status, pH, RBC membrane lipid oxidation and colloidal osmotic pressure (COP). The results indicated that bacterial growth had a modest effect on hemolysis while pH-values typical for post mortem fish muscle (6.4–6.8), and absence of glucose or albumin stimulated hemolysis. The rapid hemolysis observed at pH 6.4–6.8 correlated with lipid oxidation of the RBC membrane, while the lower hemolysis at pH 7.2–8.0 occurred with low, or without any RBC membrane lipid oxidation. When hemin was added to the RBCs at pH 6.8 hemolysis was induced without parallel RBC membrane oxidation, pointing at Hb-autoxidation and hemin-release per se as important events triggering lysis in fish muscle. Altogether, the study provided valuable findings which ultimately can aid development of new tools to combat lipid oxidation in post mortem fish muscle by limiting hemolysis.