bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiolysis of Macromolecular Organic Material in Mars‐Relevant Mineral Matrices
Authors: Fox A. C. , Eigenbrode J. L. , Freeman K. H.
Published: November 2019

The fate of organic material on Mars after deposition is crucial to interpreting the source of these molecules. Previous work has addressed how various organic compounds at millimeter depths in sediments respond to ultraviolet radiation. In contrast, this study addressed how high‐energy particle radiation (200‐MeV protons, simulating the effect of galactic cosmic rays and solar wind at depths of <4–5 cm) influences organic macromolecules in sediments. Specifically, we report the generation of organic‐acid radiolysis products after exposure to radiation doses equivalent to geological time scales (1–7 Myr). We found that formate and oxalate were produced from a variety of organic starting materials and mineral matrices. Unlike ultraviolet‐driven reactions that can invoke Fenton chemistry to produce organic acids, our work suggests that irradiation of semiconductor surfaces, such as TiO2 or possible clay minerals found on Mars, forms oxygen and hydroxyl radical species, which can break down macromolecules into organic acids. We also investigated the metastability of benzoate in multiple mineral matrices. Benzoate was added to samples prior to irradiation and persisted up to 500 kGys of exposure. Our findings suggest that organic acids are likely a major component of organic material buried at depth on Mars.
Publisher Correction: Genomic signatures of human and animal disease in the zoonotic pathogen Streptococcus suis
Authors: Weinert Lucy A. , Chaudhuri Roy R. , Wang Jinhong , Peters Sarah E. , Corander Jukka , Jombart Thibaut , Baig Abiyad , Howell Kate J. , Vehkala Minna , Välimäki Niko , Harris David , Chieu Tran Thi Bich , Van Vinh Chau Nguyen , Campbell James , Schultsz Constance , Parkhill Julian , Bentley Stephen D. , Langford Paul R. , Rycroft Andrew N. , Wren Brendan W. , Farrar Jeremy , Baker Stephen , Hoa Ngo Thi , Holden Matthew T. G. , Tucker Alexander W. , Maskell Duncan J. ,   BRaDP1T Consortium, Bossé Janine T. , Li Yanwen , Maglennon Gareth A. , Matthews Dominic , Cuccui Jon , Terra Vanessa
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
In-cell identification and measurement of RNA-protein interactions
Authors: Graindorge Antoine , Pinheiro Inês , Nawrocka Anna , Mallory Allison C. , Tsvetkov Peter , Gil Noa , Carolis Carlo , Buchholz Frank , Ulitsky Igor , Heard Edith , Taipale Mikko , Shkumatava Alena
Published: November 2019

Regulatory RNAs exert their cellular functions through RNA-binding proteins (RBPs). Identifying RNA-protein interactions is therefore key for a molecular understanding of regulatory RNAs. To date, RNA-bound proteins have been identified primarily through RNA purification followed by mass spectrometry. Here, we develop incPRINT (in cell protein-RNA interaction), a high-throughput method to identify in-cell RNA-protein interactions revealed by quantifiable luminescence. Applying incPRINT to long noncoding RNAs (lncRNAs), we identify RBPs specifically interacting with the lncRNA Firre and three functionally distinct regions of the lncRNA Xist. incPRINT confirms previously known lncRNA-protein interactions and identifies additional interactions that had evaded detection with other approaches. Importantly, the majority of the incPRINT-defined interactions are specific to individual functional regions of the large Xist transcript. Thus, we present an RNA-centric method that enables reliable identification of RNA-region-specific RBPs and is applicable to any RNA of interest.
SERS discrimination of single DNA bases in single oligonucleotides by electro-plasmonic trapping
Authors: Huang Jian-An , Mousavi Mansoureh Z. , Zhao Yingqi , Hubarevich Aliaksandr , Omeis Fatima , Giovannini Giorgia , Schütte Moritz , Garoli Denis , De Angelis Francesco
Published: November 2019

Surface-enhanced Raman spectroscopy (SERS) sensing of DNA bases by plasmonic nanopores could pave a way to novel methods for DNA analyses and new generation single-molecule sequencing platforms. The SERS discrimination of single DNA bases depends critically on the time that a DNA strand resides within the plasmonic hot spot. In fact, DNA molecules flow through the nanopores so rapidly that the SERS signals collected are not sufficient for single-molecule analysis. Here, we report an approach to control the residence time of molecules in the hot spot by an electro-plasmonic trapping effect. By directly adsorbing molecules onto a gold nanoparticle and then trapping the single nanoparticle in a plasmonic nanohole up to several minutes, we demonstrate single-molecule SERS detection of all four DNA bases as well as discrimination of single nucleobases in a single oligonucleotide. Our method can be extended easily to label-free sensing of single-molecule amino acids and proteins.
Anomalous magnetoresistance due to longitudinal spin fluctuations in a Jeff = 1/2 Mott semiconductor
Authors: Hao Lin , Wang Zhentao , Yang Junyi , Meyers D. , Sanchez Joshua , Fabbris Gilberto , Choi Yongseong , Kim Jong-Woo , Haskel Daniel , Ryan Philip J. , Barros Kipton , Chu Jiun-Haw , Dean M. P. M. , Batista Cristian D. , Liu Jian
Published: November 2019

As a hallmark of electronic correlation, spin-charge interplay underlies many emergent phenomena in doped Mott insulators, such as high-temperature superconductivity, whereas the half-filled parent state is usually electronically frozen with an antiferromagnetic order that resists external control. We report on the observation of a positive magnetoresistance that probes the staggered susceptibility of a pseudospin-half square-lattice Mott insulator built as an artificial SrIrO3/SrTiO3 superlattice. Its size is particularly large in the high-temperature insulating paramagnetic phase near the Néel transition. This magnetoresistance originates from a collective charge response to the large longitudinal spin fluctuations under a linear coupling between the external magnetic field and the staggered magnetization enabled by strong spin-orbit interaction. Our results demonstrate a magnetic control of the binding energy of the fluctuating particle-hole pairs in the Slater-Mott crossover regime analogous to the Bardeen-Cooper-Schrieffer-to-Bose-Einstein condensation crossover of ultracold-superfluids.
Disentangling the role of Africa in the global spread of H5 highly pathogenic avian influenza
Authors: Fusaro Alice , Zecchin Bianca , Vrancken Bram , Abolnik Celia , Ademun Rose , Alassane Abdou , Arafa Abdelsatar , Awuni Joseph Adongo , Couacy-Hymann Emmanuel , Coulibaly M.’ Bétiégué , Gaidet Nicolas , Go-Maro Emilie , Joannis Tony , Jumbo Simon Dickmu , Minoungou Germaine , Meseko Clement , Souley Maman Moutari , Ndumu Deo Birungi , Shittu Ismaila , Twabela Augustin , Wade Abel , Wiersma Lidewij , Akpeli Yao P. , Zamperin Gianpiero , Milani Adelaide , Lemey Philippe , Monne Isabella
Published: November 2019

The role of Africa in the dynamics of the global spread of a zoonotic and economically-important virus, such as the highly pathogenic avian influenza (HPAI) H5Nx of the Gs/GD lineage, remains unexplored. Here we characterise the spatiotemporal patterns of virus diffusion during three HPAI H5Nx intercontinental epidemic waves and demonstrate that Africa mainly acted as an ecological sink of the HPAI H5Nx viruses. A joint analysis of host dynamics and continuous spatial diffusion indicates that poultry trade as well as wild bird migrations have contributed to the virus spreading into Africa, with West Africa acting as a crucial hotspot for virus introduction and dissemination into the continent. We demonstrate varying paths of avian influenza incursions into Africa as well as virus spread within Africa over time, which reveal that virus expansion is a complex phenomenon, shaped by an intricate interplay between avian host ecology, virus characteristics and environmental variables.
Enhancing materials property prediction by leveraging computational and experimental data using deep transfer learning
Authors: Jha Dipendra , Choudhary Kamal , Tavazza Francesca , Liao Wei-keng , Choudhary Alok , Campbell Carelyn , Agrawal Ankit
Published: November 2019

The current predictive modeling techniques applied to Density Functional Theory (DFT) computations have helped accelerate the process of materials discovery by providing significantly faster methods to scan materials candidates, thereby reducing the search space for future DFT computations and experiments. However, in addition to prediction error against DFT-computed properties, such predictive models also inherit the DFT-computation discrepancies against experimentally measured properties. To address this challenge, we demonstrate that using deep transfer learning, existing large DFT-computational data sets (such as the Open Quantum Materials Database (OQMD)) can be leveraged together with other smaller DFT-computed data sets as well as available experimental observations to build robust prediction models. We build a highly accurate model for predicting formation energy of materials from their compositions; using an experimental data set of$$1,643$$1,643observations, the proposed approach yields a mean absolute error (MAE) of$$0.07$$0.07eV/atom, which is significantly better than existing machine learning (ML) prediction modeling based on DFT computations and is comparable to the MAE of DFT-computation itself.
Dynamic constriction and fission of endoplasmic reticulum membranes by reticulon
Authors: Espadas Javier , Pendin Diana , Bocanegra Rebeca , Escalada Artur , Misticoni Giulia , Trevisan Tatiana , Velasco del Olmo Ariana , Montagna Aldo , Bova Sergio , Ibarra Borja , Kuzmin Peter I. , Bashkirov Pavel V. , Shnyrova Anna V. , Frolov Vadim A. , Daga Andrea
Published: November 2019

The endoplasmic reticulum (ER) is a continuous cell-wide membrane network. Network formation has been associated with proteins producing membrane curvature and fusion, such as reticulons and atlastin. Regulated network fragmentation, occurring in different physiological contexts, is less understood. Here we find that the ER has an embedded fragmentation mechanism based upon the ability of reticulon to produce fission of elongating network branches. In Drosophila, Rtnl1-facilitated fission is counterbalanced by atlastin-driven fusion, with the prevalence of Rtnl1 leading to ER fragmentation. Ectopic expression of Drosophila reticulon in COS-7 cells reveals individual fission events in dynamic ER tubules. Consistently, in vitro analyses show that reticulon produces velocity-dependent constriction of lipid nanotubes leading to stochastic fission via a hemifission mechanism. Fission occurs at elongation rates and pulling force ranges intrinsic to the ER, thus suggesting a principle whereby the dynamic balance between fusion and fission controlling organelle morphology depends on membrane motility.
Phase-field lattice Boltzmann model for dendrites growing and moving in melt flow
Authors: Rátkai László , Pusztai Tamás , Gránásy László
Published: November 2019

The phase-field and lattice Boltzmann methods have been combined to simulate the growth of solid particles moving in melt flow. To handle mobile particles, an overlapping multigrid scheme was developed, in which each individual particle has its own moving grid, with local fields attached to it. Using this approach we were able to simulate simultaneous binary solidification, solute diffusion, melt flow, solid motion, the effect of gravity, and collision of the particles. The method has been applied for describing two possible modes of columnar to equiaxed transition in the Al–Ti system.
Prediction of room-temperature half-metallicity in layered halide double perovskites
Authors: Xu Jian , Xu Changsong , Liu Jian-Bo , Bellaiche Laurent , Xiang Hongjun , Liu Bai-Xin , Huang Bing
Published: November 2019

Half-metallic ferromagnets (HMFs) that possess intriguing physical properties with completely spin-polarized current are key candidates for high-efficiency spintronic devices. However, HMFs that could simultaneously have high Curie temperature (Tc), wide half-metallic gap (ΔHM), and large bulk magnetocrystalline anisotropy energy (MAE) are very rare, which significantly restrict their room-temperature (RT) applications. In this article, through materials screening in layered halide double perovskites (LHDPs), we have theoretically identified that Cs4FePb2Cl12, which has good crystallographic, dynamic and thermal stabilities, possesses an intrinsic half-metallic ground-state with a high Tc ~ 450 K. Interestingly, the long-range ferromagnetic ordering in bulk Cs4FePb2Cl12 is contributed by the strong super-superexchange interactions between the neighboring Fe d orbitals mediated by different anionic Cl p orbitals. The high Tc of layered Cs4FePb2Cl12 can be well maintained even in the monolayer limitation, i.e., Tc ~ 370 K for Cs4FePb2Cl12 monolayer, which is critical for nanoscale device applications. Moreover, both bulk and monolayer Cs4FePb2Cl12 can exhibit wide ΔHM ~ 0.55 eV and large MAE >320 μeV/Fe, comparable to that of the best HMFs reported in the literature. Our findings can significantly extend the potentials of LHDPs for high-temperature spintronic applications.
A simple method for sequencing the whole human mitochondrial genome directly from samples and its application to genetic testing
Authors: Yao Yue , Nishimura Motoi , Murayama Kei , Kuranobu Naomi , Tojo Satomi , Beppu Minako , Ishige Takayuki , Itoga Sakae , Tsuchida Sachio , Mori Masato , Takayanagi Masaki , Yokoyama Masataka , Yamagata Kazuyuki , Kishita Yoshihito , Okazaki Yasushi , Nomura Fumio , Matsushita Kazuyuki , Tanaka Tomoaki
Published: November 2019

Next-generation sequencing (NGS) is a revolutionary sequencing technology for analyzing genomes. However, preprocessing methods for mitochondrial DNA (mtDNA) sequencing remain complex, and it is required to develop an authenticated preprocessing method. Here, we developed a simple and easy preprocessing method based on isothermal rolling circle mtDNA amplification using commercially available reagents. Isothermal amplification of mtDNA was successfully performed using both nanoliter quantities of plasma directly and 25 ng of total DNA extracted from blood or tissue samples. Prior to mtDNA amplification, it was necessary to treat the extracted total DNA with Exonuclease V, but it was not required to treat plasma. The NGS libraries generated from the amplified mtDNA provided sequencing coverage of the entire human mitochondrial genome. Furthermore, the sequencing results successfully detected heteroplasmy in patient samples, with called mutations and variants matching those from previous, independent, Sanger sequencing analysis. Additionally, a novel single nucleotide variant was detected in a healthy volunteer. The successful analysis of mtDNA using very small samples from patients is likely to be valuable in clinical medicine, as it could reduce patient discomfort by reducing sampling-associated damage to tissues. Overall, the simple and convenient preprocessing method described herein may facilitate the future development of NGS-based clinical and forensic mtDNA tests.
Global Phylogeographic and Admixture Patterns in Grey Wolves and Genetic Legacy of An Ancient Siberian Lineage
Authors: Pilot Małgorzata , Moura Andre E. , Okhlopkov Innokentiy M. , Mamaev Nikolay V. , Alagaili Abdulaziz N. , Mohammed Osama B. , Yavruyan Eduard G. , Manaseryan Ninna H. , Hayrapetyan Vahram , Kopaliani Natia , Tsingarska Elena , Krofel Miha , Skoglund Pontus , Bogdanowicz Wiesław
Published: November 2019

The evolutionary relationships between extinct and extant lineages provide important insight into species’ response to environmental change. The grey wolf is among the few Holarctic large carnivores that survived the Late Pleistocene megafaunal extinctions, responding to that period’s profound environmental changes with loss of distinct lineages and phylogeographic shifts, and undergoing domestication. We reconstructed global genome-wide phylogeographic patterns in modern wolves, including previously underrepresented Siberian wolves, and assessed their evolutionary relationships with a previously genotyped wolf from Taimyr, Siberia, dated at 35 Kya. The inferred phylogeographic structure was affected by admixture with dogs, coyotes and golden jackals, stressing the importance of accounting for this process in phylogeographic studies. The Taimyr lineage was distinct from modern Siberian wolves and constituted a sister lineage of modern Eurasian wolves and domestic dogs, with an ambiguous position relative to North American wolves. We detected gene flow from the Taimyr lineage to Arctic dog breeds, but population clustering methods indicated closer similarity of the Taimyr wolf to modern wolves than dogs, implying complex post-divergence relationships among these lineages. Our study shows that introgression from ecologically diverse con-specific and con-generic populations was common in wolves’ evolutionary history, and could have facilitated their adaptation to environmental change.
Overestimated climate warming and climate variability due to spatially homogeneous CO2 in climate modeling over the Northern Hemisphere since the mid-19th century
Authors: Zhang Xuezhen , Li Xiaxiang , Chen Deliang , Cui Huijuan , Ge Quansheng
Published: November 2019

Since the mid-19th century, the global atmospheric CO2 concentration (ACC) has increased dramatically due to the burning of fossil fuels. Because of unequal population growth and economic development among regions, the ACC increases possess strong spatial variability. Particularly, the increase in ACC has been larger in the mid-latitudes of the Northern Hemisphere (NH) than that at high- and low-latitudes. It is widely accepted that the ACC increase is the main reason for climate change, but the potential impacts of its spatial distribution on the climate system remain unclear. Therefore, we carried out two groups of 150-year experiments with the Community Earth System Model (CESM), using both spatially inhomogeneous (hereafter the SIC experiment) and homogenous (hereafter the SHC experiment) ACC increases in their settings. We found that the models’ divergences occurred over the NH mid-latitudes, the Arctic and the western part of the tropical Pacific. SHC overestimated (underestimated) climate warming over the Artic (mid-latitudes), which may be induced by the intensified westerly and weakened meridional heat exchange between mid- and high latitudes in the NH. Over the tropical Pacific, the overestimation of climate warming may be induced by intensified Walker circulation coupled with the La Niña climate mode. For the entire NH, relative to SIC, SHC overestimated the climate warming from 1850 to 1999 by ~10%. Meanwhile, the SHC experiment also overestimated the interannual variabilities in temperature and precipitation, resulting in more serious extreme events. These findings suggest that human contributions to climate warming and increased extreme events since the industrial revolution may be overestimated when using a spatially homogenous ACC.
Early life home microbiome and hyperactivity/inattention in school-age children
Authors: Casas Lidia , Karvonen Anne M. , Kirjavainen Pirkka V. , Täubel Martin , Hyytiäinen Heidi , Jayaprakash Balamuralikrishna , Lehmann Irina , Standl Marie , Pekkanen Juha , Heinrich Joachim
Published: November 2019

This study evaluates the association between indoor microbial diversity early in life and hyperactivity/inattention symptoms in children at ages 10 and 15 years.A random sample enriched with subjects with hyperactivity/inattention at age 15 years was selected from the German LISA birth cohort. Bedroom floor dust was collected at age 3 months and 4 bacterial and fungal diversity measures [number of observed operational taxonomic units (OTUs), Chao1, Shannon and Simpson indices] were calculated from Illumina MiSeq sequencing data. Hyperactivity/inattention was based on the Strengths and Difficulties Questionnaire at ages 10 and 15 (cut-off ≥7). Adjusted associations between 4 diversity measures in tertiles and hyperactivity/inattention were investigated with weighted and survey logistic regression models. We included 226 individuals with information on microbial diversity and hyperactivity/inattention. Early life bacterial diversity was inversely associated with hyperactivity/inattention at age 10 [bacterial OTUs (medium vs low: aOR = 0.4, 95%CI = (0.2–0.8)) and Chao1 (medium vs low: 0.3 (0.1–0.5); high vs low: 0.3 (0.2–0.6)], whereas fungal diversity was directly associated [Chao1 (high vs low: 2.1 (1.1–4.0)), Shannon (medium vs low: 2.8 (1.3–5.8)), and Simpson (medium vs low: 4.7 (2.4–9.3))]. At age 15, only Shannon index was significantly associated with hyperactivity/inattention [bacteria (medium vs low: 2.3 (1.2–4.2); fungi (high vs low: 0.5 (0.3–0.9))]. In conclusion, early life exposure to microbial diversity may play a role in the psychobehavioural development. We observe heterogeneity in the direction of the associations encouraging further longitudinal studies to deepen our understanding of the characteristics of the microbial community underlying the observed associations.
2, 3-Dihydro-3β-methoxy Withaferin-A Lacks Anti-Metastasis Potency: Bioinformatics and Experimental Evidences
Authors: Chaudhary Anupama , Kalra Rajkumar S. , Malik Vidhi , Katiyar Shashank P. , Sundar Durai , Kaul Sunil C. , Wadhwa Renu
Published: November 2019

Withaferin-A is a withanolide, predominantly present in Ashwagandha (Withania somnifera). It has been shown to possess anticancer activity in a variety of human cancer cells in vitro and in vivo. Molecular mechanism of such cytotoxicity has not yet been completely understood. Withaferin-A and Withanone were earlier shown to activate p53 tumor suppressor and oxidative stress pathways in cancer cells. 2,3-dihydro-3β-methoxy analogue of Withaferin-A (3βmWi-A) was shown to lack cytotoxicity and well tolerated at higher concentrations. It, on the other hand, protected normal cells against oxidative, chemical and UV stresses through induction of anti-stress and pro-survival signaling. We, in the present study, investigated the effect of Wi-A and 3βmWi-A on cell migration and metastasis signaling. Whereas Wi-A binds to vimentin and heterogeneous nuclear ribonucleoprotein K (hnRNP-K) with high efficacy and downregulates its effector proteins, MMPs and VEGF, involved in cancer cell metastasis, 3βmWi-A was ineffective. Consistently, Wi-A, and not 3βmWi-A, caused reduction in cytoskeleton proteins (Vimentin, N-Cadherin) and active protease (u-PA) that are essential for three key steps of cancer cell metastasis (EMT, increase in cell migration and invasion).
Author Correction: Effect of diversity on growth, mortality, and loss of resilience to extreme climate events in a tropical planted forest experiment
Authors: Hutchison Chantal , Gravel Dominique , Guichard Frédéric , Potvin Catherine
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Identification of two novel breast cancer loci through large-scale genome-wide association study in the Japanese population
Authors: Low Siew-Kee , Chin Yoon Ming , Ito Hidemi , Matsuo Keitaro , Tanikawa Chizu , Matsuda Koichi , Saito Hiroko , Sakurai-Yageta Mika , Nakaya Naoki , Shimizu Atsushi , Nishizuka Satoshi S. , Yamaji Taiki , Sawada Norie , Iwasaki Motoki , Tsugane Shoichiro , Takezaki Toshiro , Suzuki Sadao , Naito Mariko , Wakai Kenji , Kamatani Yoichiro , Momozawa Yukihide , Murakami Yoshinori , Inazawa Johji , Nakamura Yusuke , Kubo Michiaki , Katagiri Toyomasa , Miki Yoshio
Published: November 2019

Genome-wide association studies (GWAS) have successfully identified about 70 genomic loci associated with breast cancer. Owing to the complexity of linkage disequilibrium and environmental exposures in different populations, it is essential to perform regional GWAS for better risk prediction. This study aimed to investigate the genetic architecture and to assess common genetic risk model of breast cancer with 6,669 breast cancer patients and 21,930 female controls in the Japanese population. This GWAS identified 11 genomic loci that surpass genome-wide significance threshold of P < 5.0 × 10−8 with nine previously reported loci and two novel loci that include rs9862599 on 3q13.11 (ALCAM) and rs75286142 on 21q22.12 (CLIC6-RUNX1). Validation study was carried out with 981 breast cancer cases and 1,394 controls from the Aichi Cancer Center. Pathway analyses of GWAS signals identified association of dopamine receptor medicated signaling and protein amino acid deacetylation with breast cancer. Weighted genetic risk score showed that individuals who were categorized in the highest risk group are approximately 3.7 times more likely to develop breast cancer compared to individuals in the lowest risk group. This well-powered GWAS is a representative study to identify SNPs that are associated with breast cancer in the Japanese population.
Endemic foot and mouth disease: pastoral in-herd disease dynamics in sub-Saharan Africa
Authors: McLachlan I. , Marion G. , McKendrick I. J. , Porphyre T. , Handel I. G. , Bronsvoort B. M. deC.
Published: November 2019

Foot and mouth disease (FMD) burden disproportionally affects Africa where it is considered endemic. Smallholder livestock keepers experience significant losses due to disease, but the dynamics and mechanisms underlying persistence at the herd-level and beyond remain poorly understood. We address this knowledge gap using stochastic, compartmental modelling to explore FMD virus (FMDV) persistence, outbreak dynamics and disease burden in individual cattle herds within an endemic setting. Our analysis suggests repeated introduction of virus from outside the herd is required for long-term viral persistence, irrespective of carrier presence. Risk of new disease exposures resulting in significant secondary outbreaks is reduced by the presence of immune individuals giving rise to a period of reduced risk, the predicted duration of which suggests that multiple strains of FMDV are responsible for observed yearly herd-level outbreaks. Our analysis suggests management of population turnover could potentially reduce disease burden and deliberate infection of cattle, practiced by local livestock keepers in parts of Africa, has little effect on the duration of the reduced risk period but increases disease burden. This work suggests that FMD control should be implemented beyond individual herds but, in the interim, herd management may be used to reduced FMD impact to livestock keepers.
Chemostratigraphic correlations across the first major trilobite extinction and faunal turnovers between Laurentia and South China
Authors: Lin Jih-Pai , Sundberg Frederick A. , Jiang Ganqing , Montañez Isabel P. , Wotte Thomas
Published: November 2019

During Cambrian Stage 4 (~514 Ma) the oceans were widely populated with endemic trilobites and three major faunas can be distinguished: olenellids, redlichiids, and paradoxidids. The lower–middle Cambrian boundary in Laurentia was based on the first major trilobite extinction event that is known as the Olenellid Biomere boundary. However, international correlation across this boundary (the Cambrian Series 2–Series 3 boundary) has been a challenge since the formal proposal of a four-series subdivision of the Cambrian System in 2005. Recently, the base of the international Cambrian Series 3 and of Stage 5 has been named as the base of the Miaolingian Series and Wuliuan Stage. This study provides detailed chemostratigraphy coupled with biostratigraphy and sequence stratigraphy across this critical boundary interval based on eight sections in North America and South China. Our results show robust isotopic evidence associated with major faunal turnovers across the Cambrian Series 2–Series 3 boundary in both Laurentia and South China. While the olenellid extinction event in Laurentia and the gradual extinction of redlichiids in South China are linked by an abrupt negative carbonate carbon excursion, the first appearance datum of Oryctocephalus indicus is currently the best horizon to achieve correlation between the two regions.
Early change in circulating tumor DNA as a potential predictor of response to chemotherapy in patients with metastatic colorectal cancer
Authors: Osumi Hiroki , Shinozaki Eiji , Yamaguchi Kensei , Zembutsu Hitoshi
Published: November 2019

The impact of ctDNA changes after chemotherapy on the clinical outcomes of patients with metastatic colorectal cancer (mCRC) remains unclear. The present study evaluated the clinical implications of the early change in ctDNA levels as a predictor of objective response and clinical outcome in mCRC patients who received chemotherapy. We investigated the effects of after/before ratio of ctDNA levels 2 and 8 weeks after initiation of second-line chemotherapy, on objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). ctDNA was detected using amplicon-based deep sequencing with a molecular barcode encompassing >240 hotspot mutations in 14 colon cancer-related genes. In multivariate analysis, as compared to baseline, patients with lower ctDNA level (≤50%) 8 weeks after initiation of chemotherapy showed significantly longer PFS and OS than the patients with higher (>50%) ctDNA level. In patients achieving a partial response or stable disease, the after/before ratio of ctDNA level 8 weeks after initiation of chemotherapy was significantly lower than those in patients with progressive disease. The present study suggests that an early change in the ctDNA level might serve as a biomarker to predict the chemotherapeutic efficacy and clinical outcomes in patients with mCRC.
Quantitative analysis of intracranial electrocorticography signals using the concept of statistical parametric mapping
Authors: Motoi Hirotaka , Jeong Jeong-Won , Juhász Csaba , Miyakoshi Makoto , Nakai Yasuo , Sugiura Ayaka , Luat Aimee F. , Sood Sandeep , Asano Eishi
Published: November 2019

Statistical parametric mapping (SPM) is a technique with which one can delineate brain activity statistically deviated from the normative mean, and has been commonly employed in noninvasive neuroimaging and EEG studies. Using the concept of SPM, we developed a novel technique for quantification of the statistical deviation of an intracranial electrocorticography (ECoG) measure from the nonepileptic mean. We validated this technique using data previously collected from 123 patients with drug-resistant epilepsy who underwent resective epilepsy surgery. We determined how the measurement of statistical deviation of modulation index (MI) from the non-epileptic mean (rated by z-score) improved the performance of seizure outcome classification model solely based on conventional clinical, seizure onset zone (SOZ), and neuroimaging variables. Here, MI is a summary measure quantifying the strength of in-situ coupling between high-frequency activity at >150 Hz and slow wave at 3–4 Hz. We initially generated a normative MI atlas showing the mean and standard deviation of slow-wave sleep MI of neighboring non-epileptic channels of 47 patients, whose ECoG sampling involved all four lobes. We then calculated ‘MI z-score’ at each electrode site. SOZ had a greater ‘MI z-score’ compared to non-SOZ in the remaining 76 patients. Subsequent multivariate logistic regression analysis and receiver operating characteristic analysis to the combined data of all patients revealed that the full regression model incorporating all predictor variables, including SOZ and ‘MI z-score’, best classified the seizure outcome with sensitivity/specificity of 0.86/0.76. The model excluding ‘MI z-score’ worsened its sensitivity/specificity to 0.86/0.48. Furthermore, the leave-one-out analysis successfully cross-validated the full regression model. Measurement of statistical deviation of MI from the non-epileptic mean on invasive recording is technically feasible. Our analytical technique can be used to evaluate the utility of ECoG biomarkers in epilepsy presurgical evaluation.
Pollinator restoration in Brazilian ecosystems relies on a small but phylogenetically-diverse set of plant families
Authors: Campbell Alistair John , Gigante Carvalheiro Luísa , Gastauer Markus , Almeida-Neto Mário , Giannini Tereza Cristina
Published: November 2019

The alarming rate of global pollinator decline has made habitat restoration for pollinators a conservation priority. At the same time, empirical and theoretical studies on plant-pollinator networks have demonstrated that plant species are not equally important for pollinator community persistence and restoration. However, the scarcity of comprehensive datasets on plant-pollinator networks in tropical ecosystems constrains their practical value for pollinator restoration. As closely-related species often share traits that determine ecological interactions, phylogenetic relationships could inform restoration programs in data-scarce regions. Here, we use quantitative bee-plant networks from Brazilian ecosystems to test if priority plant species for different restoration criteria (bee species richness and visitation rates) can be identified using interaction networks; if phylogenetic relationships alone can guide plant species selection; and how restoration criteria influence restored network properties and function. We found plant species that maximised the benefits of habitat restoration for bees (i.e., generalists and those with distinct flower-visitor species) were clustered in a small number of phylogenetically-diverse plant families, and that prioritising the recovery of bee visitation rates improved both stability and function of restored plant-pollinator networks. Our approach can help guide restoration of pollinator communities, even where information on local ecosystems is limited.
Size increase without genetic divergence in the Eurasian water shrew Neomys fodiens
Authors: Balmori-de la Puente Alfonso , Nores Carlos , Román Jacinto , Fernández-González Angel , Aymerich Pere , Gosálbez Joaquim , Escoda Lídia , Castresana Jose
Published: November 2019

When a population shows a marked morphological change, it is important to know whether that population is genetically distinct; if it is not, the novel trait could correspond to an adaptation that might be of great ecological interest. Here, we studied a subspecies of water shrew, Neomys fodiens niethammeri, which is found in a narrow strip of the northern Iberian Peninsula. This subspecies presents an abrupt increase in skull size when compared to the rest of the Eurasian population, which has led to the suggestion that it is actually a different species. Skulls obtained from owl pellets collected over the last 50 years allowed us to perform a morphometric analysis in addition to an extensive multilocus analysis based on short intron fragments successfully amplified from these degraded samples. Interestingly, no genetic divergence was detected using either mitochondrial or nuclear data. Additionally, an allele frequency analysis revealed no significant genetic differentiation. The absence of genetic divergence and differentiation revealed here indicate that the large form of N. fodiens does not correspond to a different species and instead represents an extreme case of size increase, of possible adaptive value, which deserves further investigation.
Synergies reciprocally relate end-effector and joint-angles in rhythmic pointing movements
Authors: Valk Tim A. , Mouton Leonora J. , Otten Egbert , Bongers Raoul M.
Published: November 2019

During rhythmic pointing movements, degrees of freedom (DOF) in the human action system—such as joint-angles in the arm—are assumed to covary to stabilise end-effector movement, e.g. index finger. In this paper, it is suggested that the end-effector movement and the coordination of DOF are reciprocally related in synergies that link DOF so as to produce the end-effector movement. The coordination of DOF in synergies and the relation between end-effector movement and DOF coordination received little attention, though essential to understand the principles of synergy formation. Therefore, the current study assessed how the end-effector movement related to the coordination of joint-angles during rhythmic pointing across target widths and distances. Results demonstrated that joint-angles were linked in different synergies when end-effector movements differed across conditions. Furthermore, in every condition, three joint-angles (shoulder plane of elevation, shoulder inward-outward rotation, elbow flexion-extension) largely drove the end-effector, and all joint-angles contributed to covariation that stabilised the end-effector. Together, results demonstrated synergies that produced the end-effector movement, constrained joint-angles so that they covaried to stabilise the end-effector, and differed when end-effector movement differed. Hence, end-effector and joint-angles were reciprocally related in synergies—indicating that the action system was organised as a complex dynamical system.
An epigenetic screening determines BET proteins as targets to suppress self-renewal and tumorigenicity in canine mammary cancer cells
Authors: Xavier Pedro L. P. , Cordeiro Yonara G. , Alexandre Pâmela A. , Pires Pedro R. L. , Saranholi Bruno H. , Silva Edson R. , Müller Susanne , Fukumasu Heidge
Published: November 2019

Targeting self-renewal and tumorigenicity has been proposed as a potential strategy against cancer stem cells (CSCs). Epigenetic proteins are key modulators of gene expression and cancer development contributing to regulation and maintenance of self-renewal and tumorigenicity. Here, we have screened a small-molecule epigenetic inhibitor library using 3D in vitro models in order to determine potential epigenetic targets associated with self-renewal and tumorigenicity in Canine Mammary Cancer (CMC) cells. We identified inhibition of BET proteins as a promising strategy to inhibit CMC colonies and tumorspheres formation. Low doses of (+)-JQ1 were able to downregulate important genes associated to self-renewal pathways such as WNT, NOTCH, Hedgehog, PI3K/AKT/mTOR, EGF receptor and FGF receptor in CMC tumorspheres. In addition, we observed downregulation of ZEB2, a transcription factor important for the maintenance of self-renewal in canine mammary cancer cells. Furthermore, low doses of (+)-JQ1 were not cytotoxic in CMC cells cultured in 2D in vitro models but induced G2/M cell cycle arrest accompanied by upregulation of G2/M checkpoint-associated genes including BTG2 and CCNG2. Our work indicates the BET inhibition as a new strategy for canine mammary cancers by modulating the self-renewal phenotype in tumorigenic cells such as CSCs.
Estimation of TiO2-FeO-Na2O slag viscosity through molecular dynamics simulations for an energy efficient ilmenite smelting process
Authors: Kim Youngjae , Park Hyunsik
Published: November 2019

Along with the increasing demand for the TiO2 pigment, the ilmenite smelting process has also become significant because it can utilize both rock- and sand-type ilmenite. However, due to the high liquidus temperature of the TiO2 slag system, the smelting process is highly energy consuming. In the present study, the viscosity of molten ilmenite slag was estimated using molecular dynamic simulations at a high temperature to achieve an appropriate and efficient slag design. To verify the validity of the simulation technique, experimental measurements were performed in parallel and their results were compared. The effects of FeO and Na2O addition on viscosity of TiO2 slag were also investigated. The addition of Na2O as a flux enhanced the ilmenite smelting process by not only lowering the liquidus temperature but also slowing the drastic viscosity increase. Statistical information obtained from the molecular dynamic simulations revealed a three-dimensional TiO6 octahedral network structure. The relationship between viscosity and structural change with varying FeO and Na2O concentrations was explored considering the coordination number of Ti and various bonding types.
Lowering the culture temperature corrects collagen abnormalities caused by HSP47 gene knockout
Authors: Fujii Kazunori K. , Taga Yuki , Sakai Takayuki , Ito Shinya , Hattori Shunji , Nagata Kazuhiro , Koide Takaki
Published: November 2019

Heat shock protein 47 (HSP47) is an endoplasmic reticulum (ER)-resident molecular chaperone that specifically recognizes triple helical portions of procollagens. The chaperone function of HSP47 is indispensable in mammals, and hsp47-null mice show an embryonic lethal phenotype accompanied by severe abnormalities in collagen-based tissue structures. Two leading hypotheses are currently accepted for the molecular function of HSP47 as a procollagen-specific chaperone. One is facilitation of procollagen folding by stabilizing thermally unstable triple helical folding intermediates, and the other is inhibition of procollagen aggregation or lateral association in the ER. The aim of this study was to elucidate the functional essence of this unique chaperone using fibroblasts established from hsp47−/− mouse embryos. When the cells were cultured at 37 °C, various defects in procollagen biosynthesis were observed, such as accumulation in the ER, over-modifications including prolyl hydroxylation, lysyl hydroxylation, and further glycosylation, and unusual secretion of type I collagen homotrimer. All defects were corrected by culturing the cells at a lower temperature of 33 °C. These results indicated that lowering the culture temperature compensated for the loss of HSP47. This study elucidated that HSP47 stabilizes the elongating triple helix of procollagens, which is otherwise unstable at the body temperature of mammals.
Alteration of the aggregation and spatial organization of the vector of Chagas disease, Triatoma infestans, by the parasite Trypanosoma cruzi
Authors: Depickère Stéphanie , Ramírez-Ávila Gonzalo Marcelo , Deneubourg Jean-Louis
Published: November 2019

Triatominae insects are vectors of the parasiteTrypanosoma cruzi, the etiological agent of Chagas disease affecting millions of people in Latin America. Some species, such asTriatoma infestans, live in the human neighborhood, aggregating in walls or roof cracks during the day and going out to feed blood at night. The comprehension of how sex andT. cruziinfection affect their aggregation and geotaxis is essential for understanding their spatial organization and the parasite dispersion. Experiments in laboratory-controlled conditions were carried out with groups of ten adults ofT. infestansable to explore and aggregate on a vertical surface. The influence of the sex (male vs. female) and the proportion of infected insects in the group were tested (100% of infected insects vs. a small proportion of infected insects, named infected and potentially weakly infected groups, respectively). Therefore, four distinct groups of insects were tested: infected males, infected females, potentially weakly infected males, and potentially weakly infected females, with 12, 9, 15, and 16 replicates, respectively. The insects presented a high negative geotaxis and a strong aggregation behavior whatever the sex or their infection. After an exploration phase, these behaviors were stable in time. The insects exhibited a preferential vertical position, head toward the top of the setup. Males had a higher negative geotaxis and a higher aggregation level than females. Both behaviors were enhanced in groups of 100% infected insects, the difference between sexes being maintained. According to a comparison between experimental and theoretical results, geotaxis favors the aggregation that mainly results from the inter-attraction between individuals.
The effect of immersive virtual reality on proximal and conditioned threat
Authors: Rosén Jörgen , Kastrati Granit , Reppling Aksel , Bergkvist Klas , Åhs Fredrik
Published: November 2019

Virtual reality lets the user be immersed in a 3-dimensional environment, which can enhance certain emotional responses to stimuli relative to experiencing them on a flat computer screen. We here tested whether displaying two different types of threats in immersive virtual reality enhanced threat related autonomic responses measured by skin conductance responses (SCRs). We studied innate and learned threat responses because these types of threats have been shown to depend on different neural circuits in animals. Therefore, it is possible that immersive virtual reality may modulate one of these threats but not the other. Innate threat responses were provoked by the sudden appearance of characters at proximal egocentric distance, which were compared to the sudden appearance of distant characters (proximal threat). Learned threat responses were studied by conditioning two of the characters to an electric shock (conditioned threat) and contrasting SCRs to these characters with SCRs to two other characters that were never paired with shock. We found that displaying stimuli in immersive virtual reality enhanced proximal threat responses but not conditioned threat responses. Findings show that immersive virtual reality can enhance an innate type of threat responses without affecting a learned threat response, suggesting that separate neural pathways serve these threat responses.
Exploring novel secondary metabolites from natural products using pre-processed mass spectral data
Authors: Kim Hyun Woo , Choi Seong Yeon , Jang Hyeon Seok , Ryu Byeol , Sung Sang Hyun , Yang Heejung
Published: November 2019

Many natural product chemists are working to identify a wide variety of novel secondary metabolites from natural materials and are eager to avoid repeatedly discovering known compounds. Here, we developed liquid chromatography/mass spectrometry (LC/MS) data-processing protocols for assessing high-throughput spectral data from natural sources and scoring the novelty of unknown metabolites from natural products. This approach automatically produces representative MS spectra (RMSs) corresponding to single secondary metabolites in natural sources. In this study, we used the RMSs of Agrimonia pilosa roots and aerial parts as models to reveal the structural similarities of their secondary metabolites and identify novel compounds, as well as isolation of three types of nine new compounds including three pilosanidin- and four pilosanol-type molecules and two 3-hydroxy-3-methylglutaryl (HMG)-conjugated chromones. Furthermore, we devised a new scoring system, the Fresh Compound Index (FCI), which grades the novelty of single secondary metabolites from a natural material using an in-house database constructed from 466 representative medicinal plants from East Asian countries. We expect that the FCIs of RMSs in a sample will help natural product chemists to discover other compounds of interest with similar chemical scaffolds or novel compounds and will provide insights relevant to the structural diversity and novelty of secondary metabolites in natural products.
Publisher Correction: Synaptotagmin-1 enables frequency coding by suppressing asynchronous release in a temperature dependent manner
Authors: Huson Vincent , van Boven Maaike A. , Stuefer Alexia , Verhage Matthijs , Cornelisse L. Niels
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Modeling ErbB2-p130Cas interaction to design new potential anticancer agents
Authors: Costamagna Andrea , Rossi Sebastiano Matteo , Natalini Dora , Simoni Matilde , Valabrega Giorgio , Defilippi Paola , Visentin Sonja , Ermondi Giuseppe , Turco Emilia , Caron Giulia , Cabodi Sara
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.