bluuebunny/crossref_metadata_2025_split huggingface dataset:
Climate-human interaction associated with southeast Australian megafauna extinction patterns
Authors: Saltré Frédérik , Chadoeuf Joël , Peters Katharina J. , McDowell Matthew C. , Friedrich Tobias , Timmermann Axel , Ulm Sean , Bradshaw Corey J. A. 
Published: November 2019

AbstractThe mechanisms leading to megafauna (>44 kg) extinctions in Late Pleistocene (126,000—12,000 years ago) Australia are highly contested because standard chronological analyses rely on scarce data of varying quality and ignore spatial complexity. Relevant archaeological and palaeontological records are most often also biased by differential preservation resulting in under-representated older events. Chronological analyses have attributed megafaunal extinctions to climate change, humans, or a combination of the two, but rarely consider spatial variation in extinction patterns, initial human appearance trajectories, and palaeoclimate change together. Here we develop a statistical approach to infer spatio-temporal trajectories of megafauna extirpations (local extinctions) and initial human appearance in south-eastern Australia. We identify a combined climate-human effect on regional extirpation patterns suggesting that small, mobile Aboriginal populations potentially needed access to drinkable water to survive arid ecosystems, but were simultaneously constrained by climate-dependent net landscape primary productivity. Thus, the co-drivers of megafauna extirpations were themselves constrained by the spatial distribution of climate-dependent water sources.
Non-canonical signalling mediates changes in fungal cell wall PAMPs that drive immune evasion
Authors: Pradhan Arnab , Avelar Gabriela M. , Bain Judith M. , Childers Delma , Pelletier Chloe , Larcombe Daniel E. , Shekhova Elena , Netea Mihai G. , Brown Gordon D. , Erwig Lars , Gow Neil A. R. , Brown Alistair J. P. 
Published: November 2019

AbstractTo colonise their host, pathogens must counter local environmental and immunological challenges. Here, we reveal that the fungal pathogen Candida albicans exploits diverse host-associated signals to promote immune evasion by masking of a major pathogen-associated molecular pattern (PAMP), β-glucan. Certain nutrients, stresses and antifungal drugs trigger β-glucan masking, whereas other inputs, such as nitrogen sources and quorum sensing molecules, exert limited effects on this PAMP. In particular, iron limitation triggers substantial changes in the cell wall that reduce β-glucan exposure. This correlates with reduced phagocytosis by macrophages and attenuated cytokine responses by peripheral blood mononuclear cells. Iron limitation-induced β-glucan masking depends on parallel signalling via the iron transceptor Ftr1 and the iron-responsive transcription factor Sef1, and the protein kinase A pathway. Our data reveal that C. albicans exploits a diverse range of specific host signals to trigger protective anticipatory responses against impending phagocytic attack and promote host colonisation.
ZFP161 regulates replication fork stability and maintenance of genomic stability by recruiting the ATR/ATRIP complex
Authors: Kim Wootae , Zhao Fei , Wu Rentian , Qin Sisi , Nowsheen Somaira , Huang Jinzhou , Zhou Qin , Chen Yuping , Deng Min , Guo Guijie , Luo Kuntian , Lou Zhenkun , Yuan Jian 
Published: November 2019

AbstractDNA replication stress-mediated activation of the ATR kinase pathway is important for maintaining genomic stability. In this study, we identified a zinc finger protein, ZFP161 that functions as a replication stress response factor in ATR activation. Mechanistically, ZFP161 acts as a scaffolding protein to facilitate the interaction between RPA and ATR/ATRIP. ZFP161 binds to RPA and ATR/ATRIP through distinct regions and stabilizes the RPA–ATR–ATRIP complex at stalled replication forks. This function of ZFP161 is important to the ATR signaling cascade and genome stability maintenance. In addition, ZFP161 knockout mice showed a defect in ATR activation and genomic instability. Furthermore, low expression of ZFP161 is associated with higher cancer risk and chromosomal instability. Overall, these findings suggest that ZFP161 coordinates ATR/Chk1 pathway activation and helps maintain genomic stability.
Brain-to-cervical lymph node signaling after stroke
Authors: Esposito Elga , Ahn Bum Ju , Shi Jingfei , Nakamura Yoshihiko , Park Ji Hyun , Mandeville Emiri T. , Yu Zhanyang , Chan Su Jing , Desai Rakhi , Hayakawa Ayumi , Ji Xunming , Lo Eng H. , Hayakawa Kazuhide 
Published: November 2019

AbstractAfter stroke, peripheral immune cells are activated and these systemic responses may amplify brain damage, but how the injured brain sends out signals to trigger systemic inflammation remains unclear. Here we show that a brain-to-cervical lymph node (CLN) pathway is involved. In rats subjected to focal cerebral ischemia, lymphatic endothelial cells proliferate and macrophages are rapidly activated in CLNs within 24 h, in part via VEGF-C/VEGFR3 signalling. Microarray analyses of isolated lymphatic endothelium from CLNs of ischemic mice confirm the activation of transmembrane tyrosine kinase pathways. Blockade of VEGFR3 reduces lymphatic endothelial activation, decreases pro-inflammatory macrophages, and reduces brain infarction. In vitro, VEGF-C/VEGFR3 signalling in lymphatic endothelial cells enhances inflammatory responses in co-cultured macrophages. Lastly, surgical removal of CLNs in mice significantly reduces infarction after focal cerebral ischemia. These findings suggest that modulating the brain-to-CLN pathway may offer therapeutic opportunities to ameliorate systemic inflammation and brain injury after stroke.
Sonic Hedgehog is expressed by hilar mossy cells and regulates cellular survival and neurogenesis in the adult hippocampus
Authors: Gonzalez-Reyes Luis E. , Chiang Chia-Chu , Zhang Mingming , Johnson Joshua , Arrillaga-Tamez Manuel , Couturier Nicholas H. , Reddy Neha , Starikov Lev , Capadona Jeffrey R. , Kottmann Andreas H. , Durand Dominique M. 
Published: November 2019

AbstractSonic hedgehog (Shh) is a multifunctional signaling protein governing pattern formation, proliferation and cell survival during embryogenesis. In the adult brain, Shh has neurotrophic function and is implicated in hippocampal neurogenesis but the cellular source of Shh in the hippocampus remains ill defined. Here, we utilize a gene expression tracer allele of Shh (Shh-nlacZ) which allowed the identification of a subpopulation of hilar neurons known as mossy cells (MCs) as a prominent and dynamic source of Shh within the dentate gyrus. AAV-Cre mediated ablation of Shh in the adult dentate gyrus led to a marked degeneration of MCs. Conversely, chemical stimulation of hippocampal neurons using the epileptogenic agent kainic acid (KA) increased the number of Shh+ MCs indicating that the expression of Shh by MCs confers a survival advantage during the response to excitotoxic insults. In addition, ablation of Shh in the adult dentate gyrus led to increased neural precursor cell proliferation and their migration into the subgranular cell layer demonstrating that MCs-generated Shh is a key modulator of hippocampal neurogenesis.
New Alzheimer’s disease model mouse specialized for analyzing the function and toxicity of intraneuronal Amyloid β oligomers
Authors: Ochiishi Tomoyo , Kaku Masami , Kiyosue Kazuyuki , Doi Motomichi , Urabe Takao , Hattori Nobutaka , Shimura Hideki , Ebihara Tatsuhiko 
Published: November 2019

AbstractOligomers of intracellular amyloid β protein (Aβ) are strongly cytotoxic and play crucial roles in synaptic transmission and cognitive function in Alzheimer’s disease (AD). However, there is currently no AD model mouse in which to specifically analyze the function of Aβ oligomers only. We have now developed a novel AD model mouse, an Aβ-GFP transgenic mouse (Aβ-GFP Tg), that expresses the GFP-fused human Aβ1-42 protein, which forms only Aβ oligomers within neurons throughout their life. The fusion proteins are expressed mainly in the hippocampal CA1-CA2 region and cerebral cortex, and are not secreted extracellularly. The Aβ-GFP Tg mice exhibit increased tau phosphorylation, altered spine morphology, decreased expressions of the GluN2B receptor and neuroligin in synaptic regions, attenuated hippocampal long-term potentiation, and impaired object recognition memory compared with non-Tg littermates. Interestingly, these dysfunctions have already appeared in 2–3-months-old animals. The Aβ-GFP fusion protein is bioactive and highly toxic, and induces the similar synaptic dysfunctions as the naturally generated Aβ oligomer derived from postmortem AD patient brains and synthetic Aβ oligomers. Thus, Aβ-GFP Tg mouse is a new tool specialized to analyze the function of Aβ oligomers in vivo and to find subtle changes in synapses in early symptoms of AD.
Sorsby Fundus Dystrophy Mutation in Tissue Inhibitor of Metalloproteinase 3 (TIMP3) promotes Choroidal Neovascularization via a Fibroblast Growth Factor-dependent Mechanism
Authors: Qi Jian Hua , Bell Brent , Singh Rupesh , Batoki Julia , Wolk Alyson , Cutler Alecia , Prayson Nicholas , Ali Mariya , Stoehr Heidi , Anand-Apte Bela 
Published: November 2019

AbstractChoroidal neovascularization (CNV) leads to loss of vision in patients with Sorsby Fundus Dystrophy (SFD), an inherited, macular degenerative disorder, caused by mutations in the Tissue Inhibitor of Metalloproteinase-3 (TIMP3) gene. SFD closely resembles age-related macular degeneration (AMD), which is the leading cause of blindness in the elderly population of the Western hemisphere. Variants in TIMP3 gene have recently been identified in patients with AMD. A majority of patients with AMD also lose vision as a consequence of choroidal neovascularization (CNV). Thus, understanding the molecular mechanisms that contribute to CNV as a consequence of TIMP-3 mutations will provide insight into the pathophysiology in SFD and likely the neovascular component of the more commonly seen AMD. While the role of VEGF in CNV has been studied extensively, it is becoming increasingly clear that other factors likely play a significant role. The objective of this study was to test the hypothesis that basic Fibroblast Growth Factor (bFGF) regulates SFD-related CNV. In this study we demonstrate that mice expressing mutant TIMP3 (Timp3S179C/S179C) showed reduced MMP inhibitory activity with an increase in MMP2 activity and bFGF levels, as well as accentuated CNV leakage when subjected to laser injury. S179C mutant-TIMP3 in retinal pigment epithelial (RPE) cells showed increased secretion of bFGF and conditioned medium from these cells induced increased angiogenesis in endothelial cells. These studies suggest that S179C-TIMP3 may promote angiogenesis and CNV via a FGFR-1-dependent pathway by increasing bFGF release and activity.
A mass spectrometry guided approach for the identification of novel vaccine candidates in gram-negative pathogens
Authors: Hornburg Daniel , Kruse Tobias , Anderl Florian , Daschkin Christina , Semper Raphaela P. , Klar Kathrin , Guenther Anna , Mejías-Luque Raquel , Schneiderhan-Marra Nicole , Mann Matthias , Meissner Felix , Gerhard Markus 
Published: November 2019

AbstractVaccination is the most effective method to prevent infectious diseases. However, approaches to identify novel vaccine candidates are commonly laborious and protracted. While surface proteins are suitable vaccine candidates and can elicit antibacterial antibody responses, systematic approaches to define surfomes from gram-negatives have rarely been successful. Here we developed a combined discovery-driven mass spectrometry and computational strategy to identify bacterial vaccine candidates and validate their immunogenicity using a highly prevalent gram-negative pathogen, Helicobacter pylori, as a model organism. We efficiently isolated surface antigens by enzymatic cleavage, with a design of experiment based strategy to experimentally dissect cell surface-exposed from cytosolic proteins. From a total of 1,153 quantified bacterial proteins, we thereby identified 72 surface exposed antigens and further prioritized candidates by computational homology inference within and across species. We next tested candidate-specific immune responses. All candidates were recognized in sera from infected patients, and readily induced antibody responses after vaccination of mice. The candidate jhp_0775 induced specific B and T cell responses and significantly reduced colonization levels in mouse therapeutic vaccination studies. In infected humans, we further show that jhp_0775 is immunogenic and activates IFNγ secretion from peripheral CD4+ and CD8+ T cells. Our strategy provides a generic preclinical screening, selection and validation process for novel vaccine candidates against gram-negative bacteria, which could be employed to other gram-negative pathogens.
Higher body mass index is linked to altered hypothalamic microstructure
Authors: Thomas K. , Beyer F. , Lewe G. , Zhang R. , Schindler S. , Schönknecht P. , Stumvoll M. , Villringer A. , Witte A. V. 
Published: November 2019

AbstractAnimal studies suggest that obesity-related diets induce structural changes in the hypothalamus, a key brain area involved in energy homeostasis. Whether this translates to humans is however largely unknown. Using a novel multimodal approach with manual segmentation, we here show that a higher body mass index (BMI) selectively predicted higher proton diffusivity within the hypothalamus, indicative of compromised microstructure in the underlying tissue, in a well-characterized population-based cohort (n1 = 338, 48% females, age 21–78 years, BMI 18–43 kg/m²). Results were independent from confounders and confirmed in another independent sample (n2 = 236). In addition, while hypothalamic volume was not associated with obesity, we identified a sexual dimorphism and larger hypothalamic volumes in the left compared to the right hemisphere. Using two large samples of the general population, we showed that a higher BMI specifically relates to altered microstructure in the hypothalamus, independent from confounders such as age, sex and obesity-associated co-morbidities. This points to persisting microstructural changes in a key regulatory area of energy homeostasis occurring with excessive weight. Our findings may help to better understand the pathomechanisms of obesity and other eating-related disorders.
Single Source Thermal Evaporation of Two-dimensional Perovskite Thin Films for Photovoltaic Applications
Authors: Zheng Zhuang-Hao , Lan Hua-Bin , Su Zheng-Hua , Peng Huan-Xin , Luo Jing-Ting , Liang Guang-Xing , Fan Ping 
Published: November 2019

AbstractHybrid two-dimensional (2D) halide perovskites has been widely studied due to its potential application for high performance perovskite solar cells. Understanding the relationship between microstructural and opto-electronic properties is very important for fabricating high-performance 2D perovskite solar cell. In this work, the effect of solvent annealing on grain growth was investigated to enhance the efficiency of photovoltaic devices with 2D perovskite films based on (BA)2(MA)3Pb4I13 prepared by single-source thermal evaporation. Results show that solvent annealing with the introduction of solvent vapor can effectively enhance the crystallization of the (BA)2(MA)3Pb4I13 thin films and produce denser, larger-crystal grains. The thin films also display a favorable band gap of 1.896 eV, which benefits for increasing the charge-diffusion lengths. The solvent-annealed (BA)2(MA)3Pb4I13 thin-film solar cell prepared by single-source thermal evaporation shows an efficiency range of 2.54–4.67%. Thus, the proposed method can be used to prepare efficient large-area 2D perovskite solar cells.
A contralateral wing stabilizes a hovering hawkmoth under a lateral gust
Authors: Han Jong-Seob , Han Jae-Hung 
Published: November 2019

AbstractPrevious analysis on the lateral stability of hovering insects, which reported a destabilizing roll moment due to a lateral gust, has relied on the results of a single wing without considering a presence of the contralateral wing (wing-wing interaction). Here, we investigated the presence of the contralateral wing on the aerodynamic and flight dynamic characteristics of a hovering hawkmoth under a lateral gust. By employing a dynamically scaled-up mechanical model and a servo-driven towing system installed in a water tank, we found that the presence of the contralateral wing plays a significant role in the lateral static stability. The contralateral wing mitigated an excessive aerodynamic force on the wing at the leeward side, thereby providing a negative roll moment to the body. Digital particle image velocimetry revealed an attenuated vortical system of the leading-edge vortex. An excessive effective angle of attack in the single wing case, which was caused by the root vortex of previous half stroke, was reduced by a downwash of the contralateral wing. The contralateral wing also relocated a neutral point in close proximity to the wing hinge points above the actual center of gravity, providing a practical static margin to a hovering hawkmoth.
Towards a quantitative determination of strain in Bragg Coherent X-ray Diffraction Imaging: artefacts and sign convention in reconstructions
Authors: Carnis Jérôme , Gao Lu , Labat Stéphane , Kim Young Yong , Hofmann Jan P. , Leake Steven J. , Schülli Tobias U. , Hensen Emiel J. M. , Thomas Olivier , Richard Marie-Ingrid 
Published: November 2019

AbstractBragg coherent X-ray diffraction imaging (BCDI) has emerged as a powerful technique to image the local displacement field and strain in nanocrystals, in three dimensions with nanometric spatial resolution. However, BCDI relies on both dataset collection and phase retrieval algorithms that can induce artefacts in the reconstruction. Phase retrieval algorithms are based on the fast Fourier transform (FFT). We demonstrate how to calculate the displacement field inside a nanocrystal from its reconstructed phase depending on the mathematical convention used for the FFT. We use numerical simulations to quantify the influence of experimentally unavoidable detector deficiencies such as blind areas or limited dynamic range as well as post-processing filtering on the reconstruction. We also propose a criterion for the isosurface determination of the object, based on the histogram of the reconstructed modulus. Finally, we study the capability of the phasing algorithm to quantitatively retrieve the surface strain (i.e., the strain of the surface voxels). This work emphasizes many aspects that have been neglected so far in BCDI, which need to be understood for a quantitative analysis of displacement and strain based on this technique. It concludes with the optimization of experimental parameters to improve throughput and to establish BCDI as a reliable 3D nano-imaging technique.
Using DNA-based stable isotope probing to reveal novel propionate- and acetate-oxidizing bacteria in propionate-fed mesophilic anaerobic chemostats
Authors: Wang Hui-Zhong , Lv Xiao-Meng , Yi Yue , Zheng Dan , Gou Min , Nie Yong , Hu Bing , Nobu Masaru K. , Narihiro Takashi , Tang Yue-Qin 
Published: November 2019

AbstractPropionate is one of the most important intermediates of anaerobic fermentation. Its oxidation performed by syntrophic propionate-oxidizing bacteria coupled with hydrogenotrophic methanogens is considered to be a rate-limiting step for methane production. However, the current understanding of SPOB is limited due to the difficulty of pure culture isolation. In the present study, two anaerobic chemostats fed with propionate as the sole carbon source were operated at different dilution rates (0.05 d−1 and 0.15 d−1). The propionate- and acetate-oxidizing bacteria in the two methanogenic chemostats were investigated combining DNA-stable isotope probing (DNA-SIP) and 16S rRNA gene high-throughput sequencing. The results of DNA-SIP with 13C-propionate/acetate suggested that, Smithella, Syntrophobacter, Cryptanaerobacter, and unclassified Rhodospirillaceae may be putative propionate-oxidizing bacteria; unclassified Spirochaetaceae, unclassified Synergistaceae, unclassified Elusimicrobia, Mesotoga, and Gracilibacter may contribute to acetate oxidation; unclassified Syntrophaceae and Syntrophomonas may be butyrate oxidizers. By DNA-SIP, unclassified OTUs with 16S rRNA gene abundance higher than 62% of total Bacteria in the PL chemostat and 38% in the PH chemostat were revealed to be related to the degradation of propionate. These results suggest that a variety of uncultured bacteria contribute to propionate degradation during anaerobic digestion. The functions and metabolic characteristics of these bacteria require further investigation.
Pyrrothiogatain acts as an inhibitor of GATA family proteins and inhibits Th2 cell differentiation in vitro
Authors: Nomura Shunsuke , Takahashi Hirotaka , Suzuki Junpei , Kuwahara Makoto , Yamashita Masakatsu , Sawasaki Tatsuya 
Published: November 2019

AbstractThe transcription factor GATA3 is a master regulator that modulates T helper 2 (Th2) cell differentiation and induces expression of Th2 cytokines, such as IL-4, IL-5, and IL-13. Th2 cytokines are involved in the protective immune response against foreign pathogens, such as parasites. However, excessive production of Th2 cytokines results in type-2 allergic inflammation. Therefore, the application of a GATA3 inhibitor provides a new therapeutic strategy to regulate Th2 cytokine production. Here, we established a novel high-throughput screening system for an inhibitor of a DNA-binding protein, such as a transcription factor, and identified pyrrothiogatain as a novel inhibitor of GATA3 DNA-binding activity. Pyrrothiogatain inhibited the DNA-binding activity of GATA3 and other members of the GATA family. Pyrrothiogatain also inhibited the interaction between GATA3 and SOX4, suggesting that it interacts with the DNA-binding region of GATA3. Furthermore, pyrrothiogatain significantly suppressed Th2 cell differentiation, without impairing Th1 cell differentiation, and inhibited the expression and production of Th2 cytokines. Our results suggest that pyrrothiogatain regulates the differentiation and function of Th2 cells via inhibition of GATA3 DNA binding activity, which demonstrates the efficiency of our drug screening system for the development of novel small compounds that inhibit the DNA-binding activity of transcription factors.