bluuebunny/crossref_metadata_2025 huggingface dataset:
Preliminary Evaluation of the Atmospheric Infrared Sounder Water Vapor Over China Against High‐Resolution Radiosonde Measurements
Authors: Zeng Zhaoliang , Mao Feiyue , Wang Zemin , Guo Jianping , Gui Ke , An Jiachun , Yim Steve Hung Lam , Yang Yuanjian , Zhang Baojun , Jiang Hu
Published: March 2019

The accuracy of the Atmospheric Infrared Sounder (AIRS) water vapor product in China is as yet unknown due to the lack of collocated in situ sounding observations. Based on high‐resolution soundings at 1400 Beijing time from 113 radiosonde sites across China, along with the Moderate Resolution Imaging Spectroradiometer (MODIS) and the Global Positioning System (GPS) data sets, a preliminary assessment has been conducted of AIRS water vapor mixing ratio (q) and precipitable water vapor (PWV) products in June 2013 and June 2014. Comparison between AIRS and radiosonde data suggests that the correlation coefficient (R) and mean bias of these two q products in China exhibit a distinct geographical dependence (with the highest R values in northwest China). This suggests that the AIRS q product tends to be underestimated in southeast China where cloud cover prevails, but overestimated in northwest China where cloud cover is sparse. With regard to the height‐resolved distribution, the q products from both AIRS and radiosondes tend to decrease with increasing altitude, irrespective of the particular region. The spatial distribution of AIRS PWV is consistent with that from radiosonde‐derived PWV, except in south China where the AIRS PWV data set is considerably underestimated. The accuracy of the AIRS water vapor product tends to be impaired under highly cloudy conditions, corroborating the notion of clouds affecting the retrieval of AIRS PWV. Our findings highlight the importance of afternoon sounding measurements in validating AIRS data and call for the improved understanding of the role of water vapor in the context of global climate change.
Oblique Reflections of Mars Express MARSIS Radar Signals From Ionospheric Density Structures: Raytracing Analysis
Authors: Němec F. , Andrews D. J. , Morgan D. D. , Kopf A. J. , Gurnett D. A.
Published: March 2019

Mars Advanced Radar for Subsurface and Ionosphere Sounding (MARSIS) radar sounder on board the Mars Express spacecraft revealed oblique reflections coming systematically from apparently stable density structures in the Martian ionosphere. Although these were typically interpreted by assuming a straight line propagation of the sounding signal at the speed of light, the ionospheric plasma is clearly a dispersive medium. Consequently, the ray propagation paths may be significantly bent, and, moreover, the observed time delays need to be interpreted in terms of realistic group velocities of the signal propagation. We select a single particularly well‐pronounced event with oblique reflections observable over a large range of signal frequencies, and we employ raytracing calculations to perform its detailed analysis. An isolated density structure responsible for the reflection of the sounding signal back to the spacecraft is assumed, and the relevant ionospheric signal propagation is properly evaluated. We show that initially oblique sounding signals get progressively more oblique during their propagation, imposing an upper threshold on the angular propagation distance between the spacecraft and the reflecting density structure, in line with the observations. Considering realistic propagation paths further allows us to explain the frequency dependence of the observed time delays and to accurately model the entire event. The obtained results are consistent with the spacecraft passing very close to a spatially limited density structure. We also show that the results obtained using realistic raytracing calculations are significantly different from the results obtained using additional simplifying assumptions.
Ground, Proximal, and Satellite Remote Sensing of Soil Moisture
Authors: Babaeian Ebrahim , Sadeghi Morteza , Jones Scott B. , Montzka Carsten , Vereecken Harry , Tuller Markus
Published: March 2019

Soil moisture (SM) is a key hydrologic state variable that is of significant importance for numerous Earth and environmental science applications that directly impact the global environment and human society. Potential applications include, but are not limited to, forecasting of weather and climate variability; prediction and monitoring of drought conditions; management and allocation of water resources; agricultural plant production and alleviation of famine; prevention of natural disasters such as wild fires, landslides, floods, and dust storms; or monitoring of ecosystem response to climate change. Because of the importance and wide‐ranging applicability of highly variable spatial and temporal SM information that links the water, energy, and carbon cycles, significant efforts and resources have been devoted in recent years to advance SM measurement and monitoring capabilities from the point to the global scales. This review encompasses recent advances and the state‐of‐the‐art of ground, proximal, and novel SM remote sensing techniques at various spatial and temporal scales and identifies critical future research needs and directions to further advance and optimize technology, analysis and retrieval methods, and the application of SM information to improve the understanding of critical zone moisture dynamics. Despite the impressive progress over the last decade, there are still many opportunities and needs to, for example, improve SM retrieval from remotely sensed optical, thermal, and microwave data and opportunities for novel applications of SM information for water resources management, sustainable environmental development, and food security.
A Race Against Time: Modeling Time Lags in Watershed Response
Authors: Ilampooranan Idhayachandhiran , Van Meter K. J. , Basu Nandita B.
Published: March 2019

Land use change and agricultural intensification have increased food production but at the cost of polluting surface and groundwater. Best management practices implemented to improve water quality have met with limited success. Such lack of success is increasingly attributed to legacy nutrient stores in the subsurface that may act as sources after reduction of external inputs. However, current water‐quality models lack a framework to capture these legacy effects. Here we have modified the SWAT (Soil Water Assessment Tool) model to capture the effects of nitrogen (N) legacies on water quality under multiple land‐management scenarios. Our new SWAT‐LAG model includes (1) a modified carbon‐nitrogen cycling module to capture the dynamics of soil N accumulation, and (2) a groundwater travel time distribution module to capture a range of subsurface travel times. Using a 502‐km2 Iowa watershed as a case study, we found that between 1950 and 2016, 25% of the total watershed N surplus (N Deposition + Fertilizer + Manure + N Fixation − Crop N uptake) had accumulated within the root zone, 14% had accumulated in groundwater, while 27% was lost as riverine output, and 34% was denitrified. In future scenarios, a 100% reduction in fertilizer application led to a 79% reduction in stream N load, but the SWAT‐LAG results suggest that it would take 84 years to achieve this reduction, in contrast to the 2 years predicted in the original SWAT model. The framework proposed here constitutes a first step toward modifying a widely used modeling approach to assess the effects of legacy N on the time required to achieve water‐quality goals.
Synchronous Strengthening of the Indian and East Asian Monsoons in Response to Global Warming Since the Last Deglaciation
Authors: Jiang Wenying , Leroy Suzanne A.G. , Yang Shiling , Zhang Enlou , Wang Luo , Yang Xiaoxiao , Rioual Patrick
Published: March 2019

The responses of the Indian and East Asian summer monsoons (ISM and EASM) to warming since the last deglaciation are controversial. Pollen results from a subalpine lake in the ISM area show that the Tsuga dumosa forest zone migrated at least 650 m upward during 18.6–7.1 kyr BP, indicating a gradual rise in mean annual temperature exceeding 3.9 °C. In response, grasses and deciduous and evergreen broad‐leaved trees successively colonized the mountainous environment. By contrast, the area around a lake in the EASM area was gradually occupied by temperate deciduous trees. In both areas, the maximum monsoonal precipitation occurred during 7.1–6.4 kyr BP, coinciding with peak Holocene warmth, but lagging the peak in Northern Hemisphere summer insolation by 3.9–4.6 kyr, due to delayed ice melting in northern high latitudes. Our results indicate the synchronous strengthening of the ISM and EASM in response to warming‐induced northward shifts in the Intertropical Convergence Zone.
Concordance of genetic variation that increases risk for Tourette Syndrome and that influences its underlying neurocircuitry
Authors: Mufford Mary , Cheung Josh , Jahanshad Neda , van der Merwe Celia , Ding Linda , Groenewold Nynke , Koen Nastassja , Chimusa Emile R. , Dalvie Shareefa , Ramesar Raj , Knowles James A. , Lochner Christine , Hibar Derrek P. , Paschou Peristera , van den Heuvel Odile A. , Medland Sarah E. , Scharf Jeremiah M. , Mathews Carol A. , Thompson Paul M. , Stein Dan J. ,   Psychiatric Genomics Consortium - Tourette Syndrome working group
Published: March 2019

There have been considerable recent advances in understanding the genetic architecture of Tourette Syndrome (TS) as well as its underlying neurocircuitry. However, the mechanisms by which genetic variation that increases risk for TS—and its main symptom dimensions—influence relevant brain regions are poorly understood. Here we undertook a genome-wide investigation of the overlap between TS genetic risk and genetic influences on the volume of specific subcortical brain structures that have been implicated in TS. We obtained summary statistics for the most recent TS genome-wide association study (GWAS) from the TS Psychiatric Genomics Consortium Working Group (4644 cases and 8695 controls) and GWAS of subcortical volumes from the ENIGMA consortium (30,717 individuals). We also undertook analyses using GWAS summary statistics of key symptom factors in TS, namely social disinhibition and symmetry behaviour. SNP effect concordance analysis (SECA) was used to examine genetic pleiotropy—the same SNP affecting two traits—and concordance—the agreement in single nucelotide polymorphism (SNP) effect directions across these two traits. In addition, a conditional false discovery rate (FDR) analysis was performed, conditioning the TS risk variants on each of the seven subcortical and the intracranial brain volume GWAS. Linkage disequilibrium score regression (LDSR) was used as validation of the SECA method. SECA revealed significant pleiotropy between TS and putamen (p = 2 × 10−4) and caudate (p = 4 × 10−4) volumes, independent of direction of effect, and significant concordance between TS and lower thalamic volume (p = 1 × 10−3). LDSR lent additional support for the association between TS and thalamus volume (p = 5.85 × 10−2). Furthermore, SECA revealed significant evidence of concordance between the social disinhibition symptom dimension and lower thalamus volume (p = 1 × 10−3), as well as concordance between symmetry behaviour and greater putamen volume (p = 7 × 10−4). Conditional FDR analysis further revealed novel variants significantly associated with TS (p < 8 × 10−7) when conditioning on intracranial (rs2708146,q = 0.046; and rs72853320,q = 0.035) and hippocampal (rs1922786,q = 0.001) volumes, respectively. These data indicate concordance for genetic variation involved in disorder risk and subcortical brain volumes in TS. Further work with larger samples is needed to fully delineate the genetic architecture of these disorders and their underlying neurocircuitry.
Ubiquitination of MAP1LC3B by pVHL is associated with autophagy and cell death in renal cell carcinoma
Authors: Kang Hyun Mi , Noh Kyung Hee , Chang Tae Kyung , Park Dongmin , Cho Hyun-Soo , Lim Jung Hwa , Jung Cho-Rok
Published: March 2019

Von Hippel Lindau (VHL) expression is significantly decreased in high-grade RCC, and autophagy, which is involved in tumor growth, invasion, differentiation, and metastasis, is activated in various human cancers. However, the relationship of autophagy and VHL in tumor progression remains controversial. Here, we showed that the expression levels of VHL and microtubule-associated protein 1 light chain 3B (MAP1LC3B, LC3B) were inversely correlated with various tumor grades of RCC tissues. pVHL was found to possess the LIR motif within a beta domain that interacted with MAP1LC3B and ubiquitinated it. The L101A VHL mutant failed to interact with MAP1LC3B, thereby failing to induce ubiquitination. MAP1LC3B-mediated autophagy was inhibited by functional pVHL and the ubiquitination of MAPLC3B was implicated in autophagy-induced cell death. We screened various autophagy inducers to determine the physiological function of the inhibition of LC3B-mediated autophagy by pVHL using VHL-deficient and VHL-expressing cell lines. MLN9708, a proteasome inhibitor, potently induced autophagy via the induction of MAP1LC3B and sensitized the cell to autophagy-mediated cell death in VHL-deficient and VHL-mutant (L101A) cells. In conclusion, our results showed that pVHL interacts with MAPL1LC3B and inhibits LC3B-mediated autophagy via MAP1LC3B ubiquitination. Furthermore, the activation of autophagy by the proteasome inhibitor MLN9708 induced cell death, indicating that MLN9708 can be used for VHL-deficient RCC therapy.
GABA inhibits proliferation and self-renewal of mouse retinal progenitor cell
Authors: Wang Shaojun , Du Lu , Peng Guanghua , Li Wei
Published: March 2019

Gamma-amino butyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system, including the retina, and play an important role in both regulating neurogenesis and neural stem cell proliferation. GABAa receptor has been identified in the retina, however, the function of GABAa receptor on retinal progenitor cell (RPC) is unclear. RPCs were cultured to analyze changes in cell proliferation and cell cycle distribution after GABAa receptor activation. The activation of GABAa receptor significantly inhibits RPCs proliferation, cell cycle progress, and self-renewal. Moreover, the activation of GABAa receptor leads to the up-expression of p21 and p27 and down-expression of Nestin, Pax6, Sox2, and Chx10. These results suggest that GABA acts as a negative regulator of RPCs proliferation and self-renewal.
Factors controlling surface oxygen exchange in oxides
Authors: Cao Yipeng , Gadre Milind J. , Ngo Anh T. , Adler Stuart B. , Morgan Dane D.
Published: March 2019

Reducing the working temperature of solid oxide fuel cells is critical to their increased commercialization but is inhibited by the slow oxygen exchange kinetics at the cathode, which limits the overall rate of the oxygen reduction reaction. We use ab initio methods to develop a quantitative elementary reaction model of oxygen exchange in a representative cathode material, La0.5Sr0.5CoO3−δ, and predict that under operating conditions the rate-limiting step for oxygen incorporation from O2 gas on the stable, (001)-SrO surface is lateral (surface) diffusion of O-adatoms and oxygen surface vacancies. We predict that a high vacancy concentration on the metastable CoO2 termination enables a vacancy-assisted O2 dissociation that is 102–103 times faster than the rate limiting step on the Sr-rich (La,Sr)O termination. This result implies that dramatically enhanced oxygen exchange performance could potentially be obtained by suppressing the (La,Sr)O termination and stabilizing highly active CoO2 termination.
TG-interacting factor 1 (Tgif1)-deficiency attenuates bone remodeling and blunts the anabolic response to parathyroid hormone
Authors: Saito Hiroaki , Gasser Andreas , Bolamperti Simona , Maeda Miki , Matthies Levi , Jähn Katharina , Long Courtney L. , Schlüter Hartmut , Kwiatkowski Marcel , Saini Vaibhav , Pajevic Paola Divieti , Bellido Teresita , van Wijnen Andre J. , Mohammad Khalid S. , Guise Theresa A. , Taipaleenmäki Hanna , Hesse Eric
Published: March 2019

Osteoporosis is caused by increased bone resorption and decreased bone formation. Intermittent administration of a fragment of Parathyroid hormone (PTH) activates osteoblast-mediated bone formation and is used in patients with severe osteoporosis. However, the mechanisms by which PTH elicits its anabolic effect are not fully elucidated. Here we show that the absence of the homeodomain protein TG-interacting factor 1 (Tgif1) impairs osteoblast differentiation and activity, leading to a reduced bone formation. Deletion of Tgif1 in osteoblasts and osteocytes decreases bone resorption due to an increased secretion of Semaphorin 3E (Sema3E), an osteoclast-inhibiting factor. Tgif1 is a PTH target gene and PTH treatment failed to increase bone formation and bone mass in Tgif1-deficient mice. Thus, our study identifies Tgif1 as a novel regulator of bone remodeling and an essential component of the PTH anabolic action. These insights contribute to a better understanding of bone metabolism and the anabolic function of PTH.
Humans can decipher adversarial images
Authors: Zhou Zhenglong , Firestone Chaz
Published: March 2019

Does the human mind resemble the machine-learning systems that mirror its performance? Convolutional neural networks (CNNs) have achieved human-level benchmarks in classifying novel images. These advances support technologies such as autonomous vehicles and machine diagnosis; but beyond this, they serve as candidate models for human vision itself. However, unlike humans, CNNs are “fooled” by adversarial examples—nonsense patterns that machines recognize as familiar objects, or seemingly irrelevant image perturbations that nevertheless alter the machine’s classification. Such bizarre behaviors challenge the promise of these new advances; but do human and machine judgments fundamentally diverge? Here, we show that human and machine classification of adversarial images are robustly related: In 8 experiments on 5 prominent and diverse adversarial imagesets, human subjects correctly anticipated the machine’s preferred label over relevant foils—even for images described as “totally unrecognizable to human eyes”. Human intuition may be a surprisingly reliable guide to machine (mis)classification—with consequences for minds and machines alike.
SMARCAD1 ATPase activity is required to silence endogenous retroviruses in embryonic stem cells
Authors: Sachs Parysatis , Ding Dong , Bergmaier Philipp , Lamp Boris , Schlagheck Christina , Finkernagel Florian , Nist Andrea , Stiewe Thorsten , Mermoud Jacqueline E.
Published: March 2019

Endogenous retroviruses (ERVs) can confer benefits to their host but present a threat to genome integrity if not regulated correctly. Here we identify the SWI/SNF-like remodeler SMARCAD1 as a key factor in the control of ERVs in embryonic stem cells. SMARCAD1 is enriched at ERV subfamilies class I and II, particularly at active intracisternal A-type particles (IAPs), where it preserves repressive histone methylation marks. Depletion of SMARCAD1 results in de-repression of IAPs and adjacent genes. Recruitment of SMARCAD1 to ERVs is dependent on KAP1, a central component of the silencing machinery. SMARCAD1 and KAP1 occupancy at ERVs is co-dependent and requires the ATPase function of SMARCAD1. Our findings uncover a role for the enzymatic activity of SMARCAD1 in cooperating with KAP1 to silence ERVs. This reveals ATP-dependent chromatin remodeling as an integral step in retrotransposon regulation in stem cells and advances our understanding of the mechanisms driving heterochromatin establishment.
A threonyl-tRNA synthetase-mediated translation initiation machinery
Authors: Jeong Seung Jae , Park Shinhye , Nguyen Loi T. , Hwang Jungwon , Lee Eun-Young , Giong Hoi-Khoanh , Lee Jeong-Soo , Yoon Ina , Lee Ji-Hyun , Kim Jong Hyun , Kim Hoi Kyoung , Kim Doyeun , Yang Won Suk , Kim Seon-Young , Lee Chan Yong , Yu Kweon , Sonenberg Nahum , Kim Myung Hee , Kim Sunghoon
Published: March 2019

A fundamental question in biology is how vertebrates evolved and differ from invertebrates, and little is known about differences in the regulation of translation in the two systems. Herein, we identify a threonyl-tRNA synthetase (TRS)-mediated translation initiation machinery that specifically interacts with eIF4E homologous protein, and forms machinery that is structurally analogous to the eIF4F-mediated translation initiation machinery via the recruitment of other translation initiation components. Biochemical and RNA immunoprecipitation analyses coupled to sequencing suggest that this machinery emerged as a gain-of-function event in the vertebrate lineage, and it positively regulates the translation of mRNAs required for vertebrate development. Collectively, our findings demonstrate that TRS evolved to regulate vertebrate translation initiation via its dual role as a scaffold for the assembly of initiation components and as a selector of target mRNAs. This work highlights the functional significance of aminoacyl-tRNA synthetases in the emergence and control of higher order organisms.
Artificial photosynthetic cell producing energy for protein synthesis
Authors: Berhanu Samuel , Ueda Takuya , Kuruma Yutetsu
Published: March 2019

Attempts to construct an artificial cell have widened our understanding of living organisms. Many intracellular systems have been reconstructed by assembling molecules, however the mechanism to synthesize its own constituents by self-sufficient energy has to the best of our knowledge not been developed. Here, we combine a cell-free protein synthesis system and small proteoliposomes, which consist of purified ATP synthase and bacteriorhodopsin, inside a giant unilamellar vesicle to synthesize protein by the production of ATP by light. The photo-synthesized ATP is consumed as a substrate for transcription and as an energy for translation, eventually driving the synthesis of bacteriorhodopsin or constituent proteins of ATP synthase, the original essential components of the proteoliposome. The de novo photosynthesized bacteriorhodopsin and the parts of ATP synthase integrate into the artificial photosynthetic organelle and enhance its ATP photosynthetic activity through the positive feedback of the products. Our artificial photosynthetic cell system paves the way to construct an energetically independent artificial cell.
In situ spectroscopy-guided engineering of rhodium single-atom catalysts for CO oxidation
Authors: Hülsey Max J. , Zhang Bin , Ma Zhirui , Asakura Hiroyuki , Do David A. , Chen Wei , Tanaka Tsunehiro , Zhang Peng , Wu Zili , Yan Ning
Published: March 2019

Single-atom catalysts have recently been applied in many applications such as CO oxidation. Experimental in situ investigations into this reaction, however, are limited. Hereby, we present a suite of operando/in situ spectroscopic experiments for structurally well-defined atomically dispersed Rh on phosphotungstic acid during CO oxidation. The identification of several key intermediates and the steady-state catalyst structure indicate that the reactions follow an unconventional Mars-van Krevelen mechanism and that the activation of O2 is rate-limiting. In situ XPS confirms the contribution of the heteropoly acid support while in situ DRIFT spectroscopy consolidates the oxidation state and CO adsorption of Rh. As such, direct observation of three key components, i.e., metal center, support and substrate, is achieved, providing a clearer picture on CO oxidation on atomically dispersed Rh sites. The obtained information are used to engineer structurally similar catalysts that exhibit T20 values up to 130 °C below the previously reported Rh1/NPTA.
Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis
Authors: Kelly Madison J. , So Joan , Rogers Amy J. , Gregory Gareth , Li Jason , Zethoven Magnus , Gearhart Micah D. , Bardwell Vivian J. , Johnstone Ricky W. , Vervoort Stephin J. , Kats Lev M.
Published: March 2019

The BCL6 Corepressor (BCOR) is a component of a variant Polycomb repressive complex 1 (PRC1) that is essential for normal development. Recurrent mutations in the BCOR gene have been identified in acute myeloid leukaemia and myelodysplastic syndrome among other cancers; however, its function remains poorly understood. Here we examine the role of BCOR in haematopoiesis in vivo using a conditional mouse model that mimics the mutations observed in haematological malignancies. Inactivation of Bcor in haematopoietic stem cells (HSCs) results in expansion of myeloid progenitors and co-operates with oncogenic KrasG12D in the initiation of an aggressive and fully transplantable acute leukaemia. Gene expression analysis and chromatin immunoprecipitation sequencing reveals differential regulation of a subset of PRC1-target genes including HSC-associated transcription factors such as Hoxa7/9. This study provides mechanistic understanding of how BCOR regulates cell fate decisions and how loss of function contributes to the development of leukaemia.
Aedes mosquitoes acquire and transmit Zika virus by breeding in contaminated aquatic environments
Authors: Du Senyan , Liu Yang , Liu Jianying , Zhao Jie , Champagne Clara , Tong Liangqin , Zhang Renli , Zhang Fuchun , Qin Cheng-Feng , Ma Ping , Chen Chun-Hong , Liang Guodong , Liu Qiyong , Shi Pei-Yong , Cazelles Bernard , Wang Penghua , Tian Huaiyu , Cheng Gong
Published: March 2019

Zika virus (ZIKV) is a mosquito-borne flavivirus that predominantly circulates between humans and Aedes mosquitoes. Clinical studies have shown that Zika viruria in patients persists for an extended period, and results in infectious virions being excreted. Here, we demonstrate that Aedes mosquitoes are permissive to ZIKV infection when breeding in urine or sewage containing low concentrations of ZIKV. Mosquito larvae and pupae, including from field Aedes aegypti can acquire ZIKV from contaminated aquatic systems, resulting in ZIKV infection of adult females. Adult mosquitoes can transmit infectious virions to susceptible type I/II interferon receptor-deficient (ifnagr-/-) C57BL/6 (AG6) mice. Furthermore, ZIKV viruria from infected AG6 mice can causes mosquito infection during the aquatic life stages. Our studies suggest that infectious urine could be a natural ZIKV source, which is potentially transmissible to mosquitoes when breeding in an aquatic environment.
Bromodomain and extraterminal proteins foster the core transcriptional regulatory programs and confer vulnerability in liposarcoma
Authors: Chen Ye , Xu Liang , Mayakonda Anand , Huang Mo-Li , Kanojia Deepika , Tan Tuan Zea , Dakle Pushkar , Lin Ruby Yu-Tong , Ke Xin-Yu , Said Jonathan W. , Chen Jianxiang , Gery Sigal , Ding Ling-Wen , Jiang Yan-Yi , Pang Angela , Puhaindran Mark Edward , Goh Boon Cher , Koeffler H. Phillip
Published: March 2019

Liposarcomas (LPSs) are a group of malignant mesenchymal tumors showing adipocytic differentiation. Here, to gain insight into the enhancer dysregulation and transcriptional addiction in this disease, we chart super-enhancer structures in both LPS tissues and cell lines. We identify a bromodomain and extraterminal (BET) protein-cooperated FUS-DDIT3 function in myxoid LPS and a BET protein-dependent core transcriptional regulatory circuitry consisting of FOSL2, MYC, and RUNX1 in de-differentiated LPS. Additionally, SNAI2 is identified as a crucial downstream target that enforces both proliferative and metastatic potentials to de-differentiated LPS cells. Genetic depletion of BET genes, core transcriptional factors, or SNAI2 mitigates consistently LPS malignancy. We also reveal a compelling susceptibility of LPS cells to BET protein degrader ARV-825. BET protein depletion confers additional advantages to circumvent acquired resistance to Trabectedin, a chemotherapy drug for LPS. Moreover, this study provides a framework for discovering and targeting of core oncogenic transcriptional programs in human cancers.
Boundary activated hydrogen evolution reaction on monolayer MoS2
Authors: Zhu Jianqi , Wang Zhi-Chang , Dai Huijia , Wang Qinqin , Yang Rong , Yu Hua , Liao Mengzhou , Zhang Jing , Chen Wei , Wei Zheng , Li Na , Du Luojun , Shi Dongxia , Wang Wenlong , Zhang Lixin , Jiang Ying , Zhang Guangyu
Published: March 2019

Recently, monolayer molybdenum disulphide (MoS2) has emerged as a promising and non–precious electrocatalyst for hydrogen evolution reaction. However, its performance is largely limited by the low density and poor reactivity of active sites within its basal plane. Here, we report that domain boundaries in the basal plane of monolayer MoS2 can greatly enhance its hydrogen evolution reaction performance by serving as active sites. Two types of effective domain boundaries, the 2H-2H domain boundaries and the 2H-1T phase boundaries, were investigated. Superior hydrogen evolution reaction catalytic activity, long-term stability and universality in both acidic and alkaline conditions were achieved based on a multi-hierarchy design of these two types of domain boundaries. We further demonstrate that such superior catalysts are feasible at a large scale by applying this multi-hierarchy design of domain boundaries to wafer-scale monolayer MoS2 films.
Microbial recognition by GEF-H1 controls IKKε mediated activation of IRF5
Authors: Zhao Yun , Zagani Rachid , Park Sung-Moo , Yoshida Naohiro , Shah Pankaj , Reinecker Hans-Christian
Published: March 2019

During infection, transcription factor interferon regulatory factor 5 (IRF5) is essential for the control of host defense. Here we show that the microtubule-associated guanine nucleotide exchange factor (GEF)-H1, is required for the phosphorylation of IRF5 by microbial muramyl-dipeptides (MDP), the minimal structural motif of peptidoglycan of both Gram-positive and Gram-negative bacteria. Specifically, GEF-H1 functions in a microtubule based recognition system for microbial peptidoglycans that mediates the activation of IKKε which we identify as a new upstream IKKα/β and IRF5 kinase. The deletion of GEF-H1 or dominant-negative variants of GEF-H1 prevent activation of IKKε and phosphorylation of IRF5. The GEF-H1-IKKε-IRF5 signaling axis functions independent of NOD-like receptors and is critically required for the recognition of intracellular peptidoglycans and host defenses against Listeria monocytogenes.
Overcoming the thermodynamic equilibrium of an isomerization reaction through oxidoreductive reactions for biotransformation
Authors: Liu Jing-Jing , Zhang Guo-Chang , Kwak Suryang , Oh Eun Joong , Yun Eun Ju , Chomvong Kulika , Cate Jamie H. D. , Jin Yong-Su
Published: March 2019

Isomerases perform biotransformations without cofactors but often cause an undesirable mixture of substrate and product due to unfavorable thermodynamic equilibria. We demonstrate the feasibility of using an engineered yeast strain harboring oxidoreductase reactions to overcome the thermodynamic limit of an isomerization reaction. Specifically, a yeast strain capable of consuming lactose intracellularly is engineered to produce tagatose from lactose through three layers of manipulations. First, GAL1 coding for galactose kinase is deleted to eliminate galactose utilization. Second, heterologous xylose reductase (XR) and galactitol dehydrogenase (GDH) are introduced into the ∆gal1 strain. Third, the expression levels of XR and GDH are adjusted to maximize tagatose production. The resulting engineered yeast produces 37.69 g/L of tagatose from lactose with a tagatose and galactose ratio of 9:1 in the reaction broth. These results suggest that in vivo oxidoreaductase reactions can be employed to replace isomerases in vitro for biotransformation.
Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA
Authors: Yang Ei-Wen , Bahn Jae Hoon , Hsiao Esther Yun-Hua , Tan Boon Xin , Sun Yiwei , Fu Ting , Zhou Bo , Van Nostrand Eric L. , Pratt Gabriel A. , Freese Peter , Wei Xintao , Quinones-Valdez Giovanni , Urban Alexander E. , Graveley Brenton R. , Burge Christopher B. , Yeo Gene W. , Xiao Xinshu
Published: March 2019

Allele-specific protein-RNA binding is an essential aspect that may reveal functional genetic variants (GVs) mediating post-transcriptional regulation. Recently, genome-wide detection of in vivo binding of RNA-binding proteins is greatly facilitated by the enhanced crosslinking and immunoprecipitation (eCLIP) method. We developed a new computational approach, called BEAPR, to identify allele-specific binding (ASB) events in eCLIP-Seq data. BEAPR takes into account crosslinking-induced sequence propensity and variations between replicated experiments. Using simulated and actual data, we show that BEAPR largely outperforms often-used count analysis methods. Importantly, BEAPR overcomes the inherent overdispersion problem of these methods. Complemented by experimental validations, we demonstrate that the application of BEAPR to ENCODE eCLIP-Seq data of 154 proteins helps to predict functional GVs that alter splicing or mRNA abundance. Moreover, many GVs with ASB patterns have known disease relevance. Overall, BEAPR is an effective method that helps to address the outstanding challenge of functional interpretation of GVs.
Coherent quantum control of nitrogen-vacancy center spins near 1000 kelvin
Authors: Liu Gang-Qin , Feng Xi , Wang Ning , Li Quan , Liu Ren-Bao
Published: March 2019

Quantum coherence control usually requires low temperature environments. Even for nitrogen-vacancy center spins in diamond, a remarkable exception, the coherence signal is limited to about 700 K due to the quench of the spin-dependent fluorescence at a higher temperature. Here we overcome this limit and demonstrate quantum coherence control of the electron spins of nitrogen-vacancy centers in nanodiamonds at temperatures near 1000 K. The scheme is based on initialization and readout of the spins at room temperature and control at high temperature, which is enabled by pulse laser heating and rapid diffusion cooling of nanodiamonds on amorphous carbon films. Using the diamond magnetometry based on optically detected magnetic resonance up to 800 K, we observe the magnetic phase transition of a single nickel nanoparticle at about 615 K. This work enables nano-thermometry and nano-magnetometry in the high-temperature regime.
Selective binding of a toxin and phosphatidylinositides to a mammalian potassium channel
Authors: Liu Yang , LoCaste Catherine E. , Liu Wen , Poltash Michael L. , Russell David H. , Laganowsky Arthur
Published: March 2019

G-protein-gated inward rectifying potassium channels (GIRKs) require Gβγ subunits and phosphorylated phosphatidylinositides (PIPs) for gating. Although studies have provided insight into these interactions, the mechanism of how these events are modulated by Gβγ and the binding affinity between PIPs and GIRKs remains poorly understood. Here, native ion mobility mass spectrometry is employed to directly monitor small molecule binding events to mouse GIRK2. GIRK2 binds the toxin tertiapin Q and PIPs selectively and with significantly higher affinity than other phospholipids. A mutation in GIRK2 that causes a rotation in the cytoplasmic domain, similarly to Gβγ-binding to the wild-type channel, revealed differences in the selectivity towards PIPs. More specifically, PIP isoforms known to weakly activate GIRKs have decreased binding affinity. Taken together, our results reveal selective small molecule binding and uncover a mechanism by which rotation of the cytoplasmic domain can modulate GIRK•PIP interactions.
A green metal-free fused-ring initiating substance
Authors: Deng Mucong , Feng Yongan , Zhang Wenquan , Qi Xiujuan , Zhang Qinghua
Published: March 2019

Over the past century, the search for lead-free, environmentally friendly initiating substances has been a highly challenging task in the field of energetic materials. Here, an organic primary explosive featuring a fused-ring structure, 6-nitro-7-azido-pyrazol[3,4-d][1,2,3]triazine-2-oxide, was designed and synthesized through a facile two-step reaction from commercially available reagents. This organic initiating substance meets nearly all of the stringent criteria of environmentally friendly primary explosives for commercial applications: it is free of toxic metals and perchlorate, has a high density, high priming ability, unusual sensitivities towards non-explosive stimuli, excellent environmental resistance, decent thermal stability, high detonation performance, satisfactory flowability and pressure durability, and is low-cost and easy to scale-up. These combined properties and performance measures surpass the current and widely used organic primary explosive, DDNP. The fused-ring organic primary explosive reported herein may find real-world application as an initiating explosive device in the near future.
Spatial-fluxomics provides a subcellular-compartmentalized view of reductive glutamine metabolism in cancer cells
Authors: Lee Won Dong , Mukha Dzmitry , Aizenshtein Elina , Shlomi Tomer
Published: March 2019

The inability to inspect metabolic activities within subcellular compartments has been a major barrier to our understanding of eukaryotic cell metabolism. Here, we describe a spatial-fluxomics approach for inferring metabolic fluxes in mitochondria and cytosol under physiological conditions, combining isotope tracing, rapid subcellular fractionation, LC-MS-based metabolomics, computational deconvolution, and metabolic network modeling. Applied to study reductive glutamine metabolism in cancer cells, shown to mediate fatty acid biosynthesis under hypoxia and defective mitochondria, we find a previously unappreciated role of reductive IDH1 as the sole net contributor of carbons to fatty acid biosynthesis under standard normoxic conditions in HeLa cells. In murine cells with defective SDH, we find that reductive biosynthesis of citrate in mitochondria is followed by a reversed CS activity, suggesting a new route for supporting pyrimidine biosynthesis. We expect this spatial-fluxomics approach to be a highly useful tool for elucidating the role of metabolic dysfunction in human disease.
Publisher Correction: Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus
Authors: Kraemer Moritz U. G. , Reiner Robert C. , Brady Oliver J. , Messina Jane P. , Gilbert Marius , Pigott David M. , Yi Dingdong , Johnson Kimberly , Earl Lucas , Marczak Laurie B. , Shirude Shreya , Weaver Nicole Davis , Bisanzio Donal , Perkins T. Alex , Lai Shengjie , Lu Xin , Jones Peter , Coelho Giovanini E. , Carvalho Roberta G. , Van Bortel Wim , Marsboom Cedric , Hendrickx Guy , Schaffner Francis , Moore Chester G. , Nax Heinrich H. , Bengtsson Linus , Wetter Erik , Tatem Andrew J. , Brownstein John S. , Smith David L. , Lambrechts Louis , Cauchemez Simon , Linard Catherine , Faria Nuno R. , Pybus Oliver G. , Scott Thomas W. , Liu Qiyong , Yu Hongjie , Wint G. R. William , Hay Simon I. , Golding Nick
Published: March 2019

In the version of this Article originally published, the affiliation for author Catherine Linard was incorrectly stated as ‘6Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK’. The correct affiliation is ‘9Spatial Epidemiology Lab (SpELL), Universite Libre de Bruxelles, Brussels, Belgium’. The affiliation for author Hongjie Yu was also incorrectly stated as ‘11Department of Statistics, Harvard University, Cambridge, MA, USA’. The correct affiliation is ‘15School of Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China’. This has now been amended in all versions of the Article.
Etiology of 305 cases of refractory hematospermia and therapeutic options by emerging endoscopic technology
Authors: Liao Liang-Gong , Li Yan-Feng , Zhang Yong , Li Ke , Zhu Tong , Li Bo-Jun , Wang Qi , Liu Xu-Dong , Luo Yong , Zhou Bo , Jiang Jun
Published: March 2019

To investigate the surgical outcomes of vesiculoscopy on refractory hematospermia and ejaculatory duct obstruction (EDO), the clinical data (including pelvic magnetic resonance imaging (MRI) examinations and the long-term effects of endoscopic treatment) from 305 patients were analyzed. Four main etiologic groups were found on MRI. We found that 62.0% (189/305) of patients showed abnormal signal intensity in MRI investigations in the seminal vesicle (SV) area. Cystic lesions were observed in 36.7% (112/305) of the patients. The third sign was dilatation or enlargement of unilateral or bilateral SV, which were observed in 32.1% (98/305) of the patients. The fourth sign was stone formation in SV or in an adjacent cyst, which was present in 8.5% (26/305) of the patients. The transurethral endoscopy or seminal vesiculoscopy and the related procedures, including fenestration in prostatic utricle (PU), irrigation, lithotripsy, stone removal, biopsy, electroexcision, fulguration, or transurethral resection/incision of the ejaculatory duct (TURED/TUIED), chosen according to the different situations of individual patients were successfully performed in 296 patients. Fenestrations in PU+ seminal vesiculoscopy were performed in 66.6% (197/296) of cases. Seminal vesiculoscopy via the pathological opening in PU was performed in 10.8% (32/296) of cases. TURED/TUIED + seminal vesiculoscopy was performed in 12.8% (38/296) of cases, and seminal vesiculoscopy by the natural orifices of the ejaculatory duct (ED) was performed in 2.4% (7/296) of cases. Electroexcision and fulguration to the abnormal blood vessels or cavernous hemangioma at posterior urethra were performed in 7.4% (22/296) of cases. Two hundred and seventy-one patients were followed up for 6–72 months. The hematospermia of all the patients disappeared within 2–6 weeks, and 93.0% of the patients showed no further hematospermia during follow-up. No obvious postoperative complications were observed. The transurethral seminal vesiculoscopy technique and related procedures are safe and effective approaches for refractory hematospermia and EDO.
Predicting the behavioural tendency of loss aversion
Authors: Zeng Jianmin , Wang Yujiao , Zeng Jing , Cao Zhipeng , Chen Hong , Liu Yijun , Zhang Qinglin , Su Li
Published: March 2019

Loss aversion manifests itself in rejecting a gamble of gaining or losing the same amount of money with equal chance. Although loss aversion is a well-known and intensively studied phenomenon, whether individual differences in behavioural loss aversion can be predicted using scalp potentials (EEG) remains unclear. The current study measured scalp potential when subjects played a series of fair coin-toss games in three situations (high, medium and low loss conditions). We found that most people chose to bet in the low loss condition and avoided to bet in the high loss condition. However, their betting behaviour in the medium loss condition was variable, reflecting their different behavioural tendency of loss aversion. We found that late positive complex (LPC) significantly increased when subjects accepted gambles in the low loss condition (implying potential loss), relative to when they rejected gambles in the high loss condition (implying no gain and no loss), which is consistent with the previous finding that emotional stimuli can induce enhanced LPC. We further found that the difference in the scalp potentials from the above two conditions could predict behavioural tendency of loss aversion in the medium loss condition across subjects. This result demonstrated how behavioural tendency in a situation can be predicted using EEG from other situations.
Evidence of mitochondrial DNA in the chloroplast genome of Convallaria keiskei and its subsequent evolution in the Asparagales
Authors: Raman Gurusamy , Park Seongjun , Lee Eun Mi , Park SeonJoo
Published: March 2019

DNA transfer between internal organelles such as the nucleus, mitochondrion, and plastid is a well-known phenomenon in plant evolution, and DNA transfer from the plastid and mitochondrion to the nucleus, from the plastid to the mitochondrion, and from the nucleus to the mitochondrion has been well-documented in angiosperms. However, evidence of the transfer of mitochondrial DNA (mtDNA) to the plastid has only been found in three dicotyledons and one monocotyledon. In the present study, we characterised and analysed two chloroplast (cp) genome sequences of Convallaria keiskei and Liriope spicata, and found that C. keiskei has the largest cp genome (162,109 bp) in the Asparagaceae. Interestingly, C. keiskei had a ~3.3-kb segment of mtDNA in its cp genome and showed similarity with the mt gene rpl10 as a pseudogene. Further analyses revealed that mtDNA transfer only occurred in C. keiskei in the Nolinoideae, which diverged very recently (7.68 million years ago (mya); 95% highest posterior density (HPD): 14.55–2.97 mya). These findings indicate that the C. keiskei cp genome is unique amongst monocotyledon land plants, but further work is necessary to understand the direction and mechanism involved in the uptake of mtDNA by the plastid genome of C. keiskei.
Cyclin D1 protein affecting global women’s health by regulating HPV mediated adenocarcinoma of the uterine cervix
Authors: Tripathi Richa , Rath Gayatri , Jawanjal Poonam , Bharadwaj Mausumi , Mehrotra Ravi
Published: March 2019

Adenocarcinoma (ADC) of the uterine cervix (UC) is a rare form of cervical cancer (CC) caused due to the infection of Human Papilloma Virus (HPV). Cyclin D1 is one of the downstream targets of aberrantly activated Notch signaling, contribute to the etiology of CC. However, little is known about the role of Cyclin D1 in the modulation of cervical ADC and is controversial. The purpose of this study is to determine the role of Cyclin D1 protein and to elucidate the combined analysis with Notch signaling proteins in HPV associated ADCs of CC. A total of 60 biopsy samples (40 normal and 20 ADCs of CC) were analyzed for the expression of Cyclin D1 in HPV associated ADCs via immunohistochemistry and by immunoblotting. HPV-16 positive ADC patients showed a strong association with the Cyclin D1 expression (p = 0.007). The significant mean difference (p = 0.0001) and the pairwise comparison between Cyclin D1/JAG1 (p = 0.0001), and Cyclin D1/Notch-3 (p = 0.0001) were observed. The above Notch signaling proteins showed their synergistic role in modulating Cyclin D1 which in-turn regulates HPV-16 associated ADC of the uterine cervix (UC), affecting women’s global health.
Identification of piRNAs and piRNA clusters in the testes of the Mongolian horse
Authors: Li Bei , He Xiaolong , Zhao Yiping , Bai Dongyi , Bou Gerelchimeg , Zhang Xinzhuang , Su Shaofeng , Dao Leng , Liu Rui , Wang Yuejiao , Manglai Dugarjaviin
Published: March 2019

P-element induced wimpy testis-interacting RNAs (piRNAs) are essential for testicular development and spermatogenesis in mammals. Comparative analyses of the molecular mechanisms of spermatogenesis among different organisms are therefore dependent on accurate characterizations of piRNAs. At present, little is known of piRNAs in non-model organisms. Here, we characterize piRNAs in the Mongolian horse, a hardy breed that reproduces under extreme circumstances. A thorough understanding of spermatogenesis and reproduction in this breed may provide insights for the improvement of fecundity and reproductive success in other breeds. We identified 4,936,717 piRNAs and 7,890 piRNA clusters across both testicular developmental stages. Of these, 2,236,377 putative piRNAs were expressed in the mature samples only, and 2,391,271 putative piRNAs were expressed in the immature samples only. Approximately 3,016 piRNA clusters were upregulated in the mature testes as compared to the immature testes, and 4,874 piRNA clusters were downregulated. Functional and pathway analyses indicated that the candidate generating genes of the predicted piRNAs were likely involved in testicular development and spermatogenesis. Our results thus provide information about differential expression patterns in genes associated with testicular development and spermatogenesis in a non-model animal.