bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cautious Optimism and Incremental Goals Toward Stabilizing Atmospheric CO2
Authors: Ballantyne A. P. , Ciais P. , Miller J. B. 
Published: October 2018

AbstractFossil fuel emissions of CO2 to the atmosphere appear to have leveled off in recent years; however, atmospheric CO2 concentrations continue to rise. Our simple analysis shows that peaks in the growth rates of human population and fossil fuel emissions have been observed, but the growth rate of atmospheric CO2 has reached record levels and shows no indication of peaking. Before atmospheric CO2 concentrations can be stabilized at safe levels, a peak in the CO2 growth rate must be achieved.
USP7 deubiquitinates and stabilizes NOTCH1 in T-cell acute lymphoblastic leukemia
Authors: Shan Huizhuang , Li Xiangyun , Xiao Xinhua , Dai Yuting , Huang Jinyan , Song Junjun , Liu Meng , Yang Li , Lei Hu , Tong Yin , Zhou Li , Xu Hanzhang , Wu Yingli 
Published: October 2018

AbstractT-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive leukemia that is primarily caused by aberrant activation of the NOTCH1 signaling pathway. Recent studies have revealed that posttranslational modifications, such as ubiquitination, regulate NOTCH1 stability, activity, and localization. However, the specific deubiquitinase that affects NOTCH1 protein stability remains unestablished. Here, we report that ubiquitin-specific protease 7 (USP7) can stabilize NOTCH1. USP7 deubiquitinated NOTCH1 in vivo and in vitro, whereas knockdown of USP7 increased the ubiquitination of NOTCH1. USP7 interacted with NOTCH1 protein in T-ALL cells, and the MATH and UBL domains of USP7 were responsible for this interaction. Depletion of USP7 significantly suppressed the proliferation of T-ALL cells in vitro and in vivo, accompanied by downregulation of the NOTCH1 protein level. Similarly, pharmacologic inhibition of USP7 led to apoptosis of T-ALL cells. More importantly, we found that USP7 was significantly upregulated in human T-ALL cell lines and patient samples, and a USP7 inhibitor exhibited cell cytotoxicity toward primary T-ALL cells, indicating the clinical relevance of these findings. Overall, our results demonstrate that USP7 is a novel deubiquitinase that stabilizes NOTCH1. Therefore, USP7 may be a promising therapeutic target in the currently incurable T-ALL.
Oligodendrocyte differentiation of induced pluripotent stem cells derived from subjects with schizophrenias implicate abnormalities in development
Authors: McPhie Donna L. , Nehme Ralda , Ravichandran Caitlin , Babb Suzann M. , Ghosh Sulagna Dia , Staskus Alexandra , Kalinowski Amy , Kaur Rupinderjit , Douvaras Panagiotis , Du Fei , Ongur Dost , Fossati Valentina , Eggan Kevin , Cohen Bruce M. 
Published: October 2018

AbstractAbnormalities of brain connectivity and signal transduction are consistently observed in individuals with schizophrenias (SZ). Underlying these anomalies, convergent in vivo, post mortem, and genomic evidence suggest abnormal oligodendrocyte (OL) development and function and lower myelination in SZ. Our primary hypothesis was that there would be abnormalities in the number of induced pluripotent stem (iPS) cell-derived OLs from subjects with SZ. Our secondary hypothesis was that these in vitro abnormalities would correlate with measures of white matter (WM) integrity and myelination in the same subjects in vivo, estimated from magnetic resonance imaging. Six healthy control (HC) and six SZ iPS cell lines, derived from skin fibroblasts from well-characterized subjects, were differentiated into OLs. FACS analysis of the oligodendrocyte-specific surface, glycoprotein O4, was performed at three time points of development (days 65, 75, and 85) to quantify the number of late oligodendrocyte progenitor cells (OPCs) and OLs in each line. Significantly fewer O4-positive cells developed from SZ versus HC lines (95% CI 1.0: 8.6, F1,10 = 8.06, p = 0.02). The difference was greater when corrected for age (95% CI 5.4:10.4, F1,8 = 53.6, p < 0.001). A correlation between myelin content in WM in vivo, estimated by magnetization transfer ratio (MTR) and number of O4-positive cells in vitro was also observed across all time points (F1,9 = 4.3, p = 0.07), reaching significance for mature OLs at day 85 in culture (r = 0.70, p < 0.02). Low production of OPCs may be a contributing mechanism underlying WM reduction in SZ.
Oncolysis with DTT-205 and DTT-304 generates immunological memory in cured animals
Authors: Zhou Heng , Mondragón Laura , Xie Wei , Mauseth Brynjar , Leduc Marion , Sauvat Allan , Gomes-da-Silva Lígia C. , Forveille Sabrina , Iribarren Kristina , Souquere Sylvie , Bezu Lucillia , Liu Peng , Zhao Liwei , Zitvogel Laurence , Sveinbjørnsson Baldur , Eksteen J. Johannes , Rekdal Øystein , Kepp Oliver , Kroemer Guido 
Published: October 2018

AbstractOncolytic peptides and peptidomimetics are being optimized for the treatment of cancer by selecting agents with high cytotoxic potential to kill a maximum of tumor cells as well as the capacity to trigger anticancer immune responses and hence to achieve long-term effects beyond therapeutic discontinuation. Here, we report on the characterization of two novel oncolytic peptides, DTT-205 and DTT-304 that both selectively enrich in the lysosomal compartment of cancer cells yet differ to some extent in their cytotoxic mode of action. While DTT-304 can trigger the aggregation of RIP3 in ripoptosomes, coupled to the phosphorylation of MLKL by RIP3, DTT-205 fails to activate RIP3. Accordingly, knockout of either RIP3 or MLKL caused partial resistance against cell killing by DTT-304 but not DTT-205. In contrast, both agents shared common features in other aspects of pro-death signaling in the sense that their cytotoxic effects were strongly inhibited by both serum and antioxidants, partially reduced by lysosomal inhibition with bafilomycin A1 or double knockout of Bax and Bak, yet totally refractory to caspase inhibition. Both DTT-304 and DTT-205 caused the exposure of calreticulin at the cell surface, as well as the release of HMGB1 from the cells. Mice bearing established subcutaneous cancers could be cured by local injection of DTT-205 or DTT-304, and this effect depended on T lymphocytes, as it led to the establishment of a long-term memory response against tumor-associated antigens. Thus, mice that had been cured from cancer by the administration of DTT compounds were refractory against rechallenge with the same cancer type several months after the disappearance of the primary lesion. In summary, DTT-205 and DTT-304 both have the capacity to induce immunotherapeutic oncolysis.
Ultrafast carbon monoxide photolysis and heme spin-crossover in myoglobin via nonadiabatic quantum dynamics
Authors: Falahati Konstantin , Tamura Hiroyuki , Burghardt Irene , Huix-Rotllant Miquel 
Published: October 2018

AbstractLight absorption of myoglobin triggers diatomic ligand photolysis and a spin crossover transition of iron(II) that initiate protein conformational change. The photolysis and spin crossover reactions happen concurrently on a femtosecond timescale. The microscopic origin of these reactions remains controversial. Here, we apply quantum wavepacket dynamics to elucidate the ultrafast photochemical mechanism for a heme–carbon monoxide (heme–CO) complex. We observe coherent oscillations of the Fe–CO bond distance with a period of 42 fs and an amplitude of ∼1 Å. These nuclear motions induce pronounced geometric reorganization, which makes the CO dissociation irreversible. The reaction is initially dominated by symmetry breaking vibrations inducing an electron transfer from porphyrin to iron. Subsequently, the wavepacket relaxes to the triplet manifold in ∼75 fs and to the quintet manifold in ∼430 fs. Our results highlight the central role of nuclear vibrations at the origin of the ultrafast photodynamics of organometallic complexes.
Line excitation array detection fluorescence microscopy at 0.8 million frames per second
Authors: Martin Chris , Li Tianqi , Hegarty Evan , Zhao Peisen , Mondal Sudip , Ben-Yakar Adela 
Published: October 2018

AbstractThree-dimensional, fluorescence imaging methods with ~1 MHz frame rates are needed for high-speed, blur-free flow cytometry and capturing volumetric neuronal activity. The frame rates of current imaging methods are limited to kHz by the photon budget, slow camera readout, and/or slow laser beam scanners. Here, we present line excitation array detection (LEAD) fluorescence microscopy, a high-speed imaging method capable of providing 0.8 million frames per second. The method performs 0.8 MHz line-scanning of an excitation laser beam using a chirped signal-driven longitudinal acousto-optic deflector to create a virtual light-sheet, and images the field-of-view with a linear photomultiplier tube array to generate a 66 × 14 pixel frame each scan cycle. We implement LEAD microscopy as a blur-free flow cytometer for Caenorhabditis elegans moving at 1 m s−1 with 3.5-µm resolution and signal-to-background ratios >200. Signal-to-noise measurements indicate future LEAD fluorescence microscopes can reach higher resolutions and pixels per frame without compromising frame rates.
A diverse suite of pharmaceuticals contaminates stream and riparian food webs
Authors: Richmond Erinn K. , Rosi Emma J. , Walters David M. , Fick Jerker , Hamilton Stephen K. , Brodin Tomas , Sundelin Anna , Grace Michael R. 
Published: October 2018

AbstractA multitude of biologically active pharmaceuticals contaminate surface waters globally, yet their presence in aquatic food webs remain largely unknown. Here, we show that over 60 pharmaceutical compounds can be detected in aquatic invertebrates and riparian spiders in six streams near Melbourne, Australia. Similar concentrations in aquatic invertebrate larvae and riparian predators suggest direct trophic transfer via emerging adult insects to riparian predators that consume them. As representative vertebrate predators feeding on aquatic invertebrates, platypus and brown trout could consume some drug classes such as antidepressants at as much as one-half of a recommended therapeutic dose for humans based on their estimated prey consumption rates, yet the consequences for fish and wildlife of this chronic exposure are unknown. Overall, this work highlights the potential exposure of aquatic and riparian biota to a diverse array of pharmaceuticals, resulting in exposures to some drugs that are comparable to human dosages.
Candida albicans gains azole resistance by altering sphingolipid composition
Authors: Gao Jiaxin , Wang Haitao , Li Zeyao , Wong Ada Hang-Heng , Wang Yi-Zheng , Guo Yahui , Lin Xin , Zeng Guisheng , Liu Haoping , Wang Yue , Wang Jianbin 
Published: October 2018

AbstractFungal infections by drug-resistant Candida albicans pose a global public health threat. However, the pathogen’s diploid genome greatly hinders genome-wide investigations of resistance mechanisms. Here, we develop an efficient piggyBac transposon-mediated mutagenesis system using stable haploid C. albicans to conduct genome-wide genetic screens. We find that null mutants in either gene FEN1 or FEN12 (encoding enzymes for the synthesis of very-long-chain fatty acids as precursors of sphingolipids) exhibit resistance to fluconazole, a first-line antifungal drug. Mass-spectrometry analyses demonstrate changes in cellular sphingolipid composition in both mutants, including substantially increased levels of several mannosylinositolphosphoceramides with shorter fatty-acid chains. Treatment with fluconazole induces similar changes in wild-type cells, suggesting a natural response mechanism. Furthermore, the resistance relies on a robust upregulation of sphingolipid biosynthesis genes. Our results shed light into the mechanisms underlying azole resistance, and the new transposon-mediated mutagenesis system should facilitate future genome-wide studies of C. albicans.
Direct observation of selective autophagy induction in cells and tissues by self-assembled chiral nanodevice
Authors: Sun Maozhong , Hao Tiantian , Li Xiaoyun , Qu Aihua , Xu Liguang , Hao Changlong , Xu Chuanlai , Kuang Hua 
Published: October 2018

AbstractThe interactions between chiral nanomaterials and organisms are still challenging and mysterious. Here, a chiral nanodevice made of yolk–shell nanoparticles tetrahedron (UYTe), centralized with upconversion nanoparticles (UCNPs), was fabricated to induce autophagy in vivo. The proposed chiral nanodevice displayed a tunable circular dichroism (CD) signal when modified with different enantiomers of glutathione (GSH). Notably, UYTe showed significant chirality-dependent autophagy-inducing ability afterd-GSH-modification because the enhanced oxidative stress and accumulation in living cell. The activation of autophagy resulted in the reduced intracellular CD intensity from the disassembly of the structure. The intracellular ATP concentration was simultaneously enhanced in response to autophagy activity, which was quantitatively bio-imaged with the upconversion luminescence (UCL) signal of the UCNP that escaped from UYTe. The autophagy effect induced in vivo by the chiral UYTe was also visualized with UCL imaging, demonstrating the great potential utility of the chiral nanostructure for cellular biological applications.
Locking loop movement in the ubiquinone pocket of complex I disengages the proton pumps
Authors: Cabrera-Orefice Alfredo , Yoga Etienne Galemou , Wirth Christophe , Siegmund Karin , Zwicker Klaus , Guerrero-Castillo Sergio , Zickermann Volker , Hunte Carola , Brandt Ulrich 
Published: October 2018

AbstractComplex I (proton-pumping NADH:ubiquinone oxidoreductase) is the largest enzyme of the mitochondrial respiratory chain and a significant source of reactive oxygen species (ROS). We hypothesized that during energy conversion by complex I, electron transfer onto ubiquinone triggers the concerted rearrangement of three protein loops of subunits ND1, ND3, and 49-kDa thereby generating the power-stoke driving proton pumping. Here we show that fixing loop TMH1-2ND3 to the nearby subunit PSST via a disulfide bridge introduced by site-directed mutagenesis reversibly disengages proton pumping without impairing ubiquinone reduction, inhibitor binding or the Active/Deactive transition. The X-ray structure of mutant complex I indicates that the disulfide bridge immobilizes but does not displace the tip of loop TMH1-2ND3. We conclude that movement of loop TMH1-2ND3 located at the ubiquinone-binding pocket is required to drive proton pumping corroborating one of the central predictions of our model for the mechanism of energy conversion by complex I proposed earlier.
Chemical shifts in molecular solids by machine learning
Authors: Paruzzo Federico M. , Hofstetter Albert , Musil Félix , De Sandip , Ceriotti Michele , Emsley Lyndon 
Published: October 2018

AbstractDue to their strong dependence on local atonic environments, NMR chemical shifts are among the most powerful tools for strucutre elucidation of powdered solids or amorphous materials. Unfortunately, using them for structure determination depends on the ability to calculate them, which comes at the cost of high accuracy first-principles calculations. Machine learning has recently emerged as a way to overcome the need for quantum chemical calculations, but for chemical shifts in solids it is hindered by the chemical and combinatorial space spanned by molecular solids, the strong dependency of chemical shifts on their environment, and the lack of an experimental database of shifts. We propose a machine learning method based on local environments to accurately predict chemical shifts of molecular solids and their polymorphs to within DFT accuracy. We also demonstrate that the trained model is able to determine, based on the match between experimentally measured and ML-predicted shifts, the structures of cocaine and the drug 4-[4-(2-adamantylcarbamoyl)-5-tert-butylpyrazol-1-yl]benzoic acid.
Sequence based prediction of enhancer regions from DNA random walk
Authors: Singh Anand Pratap , Mishra Sarthak , Jabin Suraiya 
Published: October 2018

AbstractRegulatory elements play a critical role in development process of eukaryotic organisms by controlling the spatio-temporal pattern of gene expression. Enhancer is one of these elements which contributes to the regulation of gene expression through chromatin loop or eRNA expression. Experimental identification of a novel enhancer is a costly exercise, due to which there is an interest in computational approaches to predict enhancer regions in a genome. Existing computational approaches to achieve this goal have primarily been based on training of high-throughput data such as transcription factor binding sites (TFBS), DNA methylation, and histone modification marks etc. On the other hand, purely sequence based approaches to predict enhancer regions are promising as they are not biased by the complexity or context specificity of such datasets. In sequence based approaches, machine learning models are either directly trained on sequences or sequence features, to classify sequences as enhancers or non-enhancers. In this paper, we derived statistical and nonlinear dynamic features along with k-mer features from experimentally validated sequences taken from Vista Enhancer Browser through random walk model and applied different machine learning based methods to predict whether an input test sequence is enhancer or not. Experimental results demonstrate the success of proposed model based on Ensemble method with area under curve (AUC) 0.86, 0.89, and 0.87 in B cells, T cells, and Natural killer cells for histone marks dataset.
Comparative genomics of the Erwinia and Enterobacter olive fly endosymbionts
Authors: Estes Anne M. , Hearn David J. , Agrawal Sonia , Pierson Elizabeth A. , Dunning Hotopp Julie C. 
Published: October 2018

AbstractThe pestivorous tephritid olive fly has long been known as a frequent host of the obligately host-associated bacterial endosymbiont, Erwinia dacicola, as well as other facultative endosymbionts. The genomes of Erwinia dacicola and Enterobacter sp. OLF, isolated from a California olive fly, encode the ability to supplement amino acids and vitamins missing from the olive fruit on which the larvae feed. The Enterobacter sp. OLF genome encodes both uricase and ureases, and the Er. dacicola genome encodes an allantoate transport pathway, suggesting that bird feces or recycling the fly’s waste products may be important sources of nitrogen. No homologs to known nitrogenases were identified in either bacterial genome, despite suggestions of their presence from experiments with antibiotic-treated flies. Comparisons between the olive fly endosymbionts and their free-living relatives revealed similar GC composition and genome size. The Er. dacicola genome has fewer genes for amino acid metabolism, cell motility, and carbohydrate transport and metabolism than free-living Erwinia spp. while having more genes for cell division, nucleotide metabolism and replication as well as mobile elements. A 6,696 bp potential lateral gene transfer composed primarily of amino acid synthesis and transport genes was identified that is also observed in Pseudomonas savastanoii pv savastanoii, the causative agent of olive knot disease.
NDVI dynamics under changing meteorological factors in a shallow lake in future metropolitan, semiarid area in North China
Authors: Zhang Yunlong , Wang Xuan , Li Chunhui , Cai Yanpeng , Yang Zhifeng , Yi Yujun 
Published: October 2018

AbstractThree meteorological parameters, including one parameter representing water conditions (i.e., precipitation) and two parameters representing energy conditions (i.e., net radiation and air temperature), were used to make an in-depth analysis of the response of Normalized Difference Vegetation Index (NDVI) dynamics to climate change in Lake Baiyangdian, a shallow lake located in Xiong’an New Area (XNA), a future metropolitan in North China. The results showed that the vegetation coverage of the entire area remained at a medium level with average NDVI being 0.46 during 2000–2015. At a yearly scale, water was the key factor controlling the reed growth in Lake Baiyangdian. NDVI variations in each season had different water/energy driving factors. In spring, summer and autumn, vegetation growth was mainly affected by net radiation, air temperature and air temperature, respectively. Time-lags between NDVI and the meteorological parameters varied from parameters and seasons. Taken together, this research broadened our cognition about response characteristics of NDVI dynamics to water and energy variations through adding an important meteorological parameter (i.e., net radiation). With the rapid construction of XNA, it could be helpful for accurately understanding impacts of climate change on vegetation growth and be beneficial for effective ecosystem management in water shortage areas.
Complex Role of Capsaicin-Sensitive Afferents in the Collagen Antibody-Induced Autoimmune Arthritis of the Mouse
Authors: Borbély Éva , Kiss Tamás , Szabadfi Krisztina , Pintér Erika , Szolcsányi János , Helyes Zsuzsanna , Botz Bálint 
Published: October 2018

AbstractCapsaicin-sensitive afferents have complex regulatory functions in the joints orchestrated via neuropeptides. This study aimed to determine their role in the collagen-antibody induced rheumatoid arthritis model. Capsaicin-sensitive nerves were defunctionalized by the capsaicin receptor agonist resiniferatoxin in C57Bl/6 mice. Arthritis was induced by the ArithroMab antibody cocktail and adjuvant. Arthritis was monitored by measuring body weight, joint edema by plethysmometry, arthritis severity by clinical scoring, mechanonociceptive threshold by plantar esthesiometry, thermonociceptive threshold by hot plate, cold tolerance by paw withdrawal latency from 0 °C water. Grasping ability was determined by the wire-grid grip test. Bone structure was evaluated byin vivomicro-CT and histology. Arthritic animals developed a modest joint edema, mechanical and cold hyperalgesia, weight loss, and a diminished grasping function, while thermal hyperalgesia is absent in the model. Desensitised mice displayed reduced arthritis severity, edema, and mechanical hyperalgesia, however, cold hyperalgesia was significantly greater in this group. Arthritic controls displayed a transient decrease of bone volume and an increased porosity, while bone density and trabecularity increased in desensitised mice. The activation of capsaicin-sensitive afferents increases joint inflammation and mechanical hyperalgesia, but decreases cold allodynia. It also affects inflammatory bone structural changes by promoting bone resorption.