bluuebunny/crossref_metadata_2025 huggingface dataset:
Free Womb Law, Legal Asynchronies, and Migrations
Authors: Candioti Magdalena
Published: January 2020

This article analyzes in depth the history of Petrona, an enslaved woman sold in Santa Fe (Argentina), sent to Buenos Aires and later possibly to Montevideo (Uruguay). By reconstructing her case, the article demonstrates how the legal status of enslaved persons was affected by the redefinitions of jurisdictions and by the forced or voluntary crossings between political units. This study also shows the circulation and uses of the Free Womb law in Argentina and Uruguay and traces legal experts’ debates over its meaning. At the same time, it reflects on the knowledge enslaved people had of those abolitionist norms and how they used them to resist forced relocations, attempt favorable migrations, or achieve full freedom. The article crosses analytical dimensions and historiographies—legal, social, and political— and articulates them by reflecting more broadly on these factors: the impact of the revolution of independence on enslaved persons’ lives, the scarce circulation of abolitionist public discourse in Río de la Plata, the gendered bias of the process, and the central yet untold uses of antislavery rhetoric in the national narratives.
The “Government of the Sertões and Indians”
Authors: Chambouleyron Rafael
Published: January 2020

This article discusses the role played by the production of sugar and cane liquor (aguardente) in the seventeenth and early eighteenth-century Amazon region. It shows how the development of sugar production had a double significance: sugar plantations had to produce a commodity that could be exported so as to generate revenues for the Royal Treasury, but they also had to produce aguardente for domestic consumption (including by those Indians who worked for the Portuguese). This domestic production provoked distrust on the part of the Crown, since it was believed to threaten sugar production overall. Nevertheless, aguardente production became a central element in the Portuguese dominion of the sertões (or sertão, the hinterland), while continuing to increase the revenues of the royal treasury.
Isfahan Twins Registry (ITR): An Invaluable Platform for Epidemiological and Epigenetic Studies: Design and Methodology of ITR
Authors: Gharipour Mojgan , Haghjooy Javanmard Shaghayegh , Mansourian Marjan , Sabri Mohammadreza , Khosravi Elham , Dianatkhah Minoo , Sadeghian Ladan , Jabarzare Zahra , Sarrafzadegan Nizal
Published: January 2020

Twin studies are one of the main tools for studying the interaction between genes and the environment in the development of complex diseases such as cancers, cardiovascular diseases and diabetes. The Isfahan Twin Registry (ITR) was launched in Isfahan in 2017 as a pilot study to establish a nationwide twin registry in Iran and aims to obtain comprehensive information about complex diseases and their risk factors from twins and multiples living in Isfahan. ITR will continue to recruit twins and multiples until all twins residing in Isfahan are registered in the registry. Twins are identified from welfare agencies, public health homes, maternity hospitals, Persian Twins Association and the local media. Demographic information, twin similarities, lifestyle, family history of diseases and past medical history are collected using validated questionnaires. Anthropometric measurements and blood pressure are measured by health professionals. Hematology panel, fasting blood sugar, total cholesterol, low-density lipoprotein, high-density lipoprotein, aspartate aminotransferase, alanine aminotransferase and quantitative C-reactive protein are measured by an automated analyzer. Extra samples are obtained for future studies. For twins aged under 6 years, parents complete the questionnaires for their children and a brief questionnaire for themselves. Currently, 998 persons (395 pairs and 67 multiples) are registered in the ITR and have provided their data. Results of preliminary data analysis are discussed in this article. We plan to carry out longitudinal assessments. ITR can play an important role in future epigenetic, biomarkers and omics studies using the biobank materials.
Effect of bicyclopyrone herbicide on sweetpotato and Palmer amaranth (Amaranthus palmeri)
Authors: Lindley Jennifer J. , Jennings Katherine M. , Monks David W. , Chaudhari Sushila , Schultheis Jonathan R. , Waldschmidt Matthew , Brownie Cavell
Published: January 2020

Management options are needed to limit sweetpotato yield loss due to weeds. Greenhouse studies were conducted in 2018 in Greensboro, NC, and in the field from 2016 to 2018 in Clinton, NC, to evaluate the effect of bicyclopyrone on sweetpotato and Palmer amaranth (field only). In greenhouse studies, Covington and NC04-531 clones were treated with bicyclopyrone (0, 25, 50, 100, or 150 g ai ha−1) either preplant (PP; i.e., immediately before transplanting) or post-transplant (PT; i.e., on the same day after transplanting). Sweetpotato plant injury and stunting increased, and vine length and shoot dry weight decreased with increasing rate of bicyclopyrone regardless of clone or application timing. In field studies, Beauregard (2016) or Covington (2017 and 2018) sweetpotato clones were treated with bicyclopyrone at 50 g ha−1 PP, flumioxazin at 107 g ai ha−1 PP, bicyclopyrone at 50 or 100 g ha−1 PP followed by (fb) S-metolachlor at 800 g ai ha−1 PT, flumioxazin at 107 g ha−1 PP fb S-metolachlor at 800 g ha−1 PT, flumioxazin at 107 g ha−1 PP fb S-metolachlor at 800 g ha−1 PT fb bicyclopyrone at 50 g ha−1 PT-directed, and clomazone at 420 g ai ha−1 PP fb S-metolachlor at 800 g ha−1 PT. Bicyclopyrone PP at 100 g ha−1 fb S-metolachlor PT caused 33% or greater crop stunting and 44% or greater marketable yield reduction compared with the weed-free check in 2016 (Beauregard) and 2017 (Covington). Bicyclopyrone PP at 50 g ha−1 alone or fb S-metolachlor PT resulted in 12% or less injury and similar no. 1 and jumbo yields as the weed-free check in 2 of 3 yr. Injury to Covington from bicyclopyrone PT-directed was 4% or less at 4 or 5 wk after transplanting and marketable yield was similar to that of the weed-free check in 2017 and 2018.
Mean State Biases and Interannual Variability Affect Perceived Sensitivities of the Madden‐Julian Oscillation to Air‐Sea Coupling
Authors: Klingaman N. P. , Demott C. A.
Published: January 2020

Atmosphere‐ocean feedbacks often improve the Madden‐Julian oscillation (MJO) in climate models, but these improvements are balanced by mean state biases that can degrade the MJO through changing the basic state on which the MJO operates. The Super‐Parameterized Community Atmospheric Model (SPCAM3) produces perhaps the best representation of the MJO among contemporary models, which improves further in a coupled configuration (SPCCSM3) despite considerable mean state biases in tropical sea surface temperatures and rainfall. We implement an atmosphere‐ocean‐mixed‐layer configuration of SPCAM3 (SPCAM3‐KPP) and use a flux‐correction technique to isolate the effects of coupling and mean state biases on the MJO. When constrained to the observed ocean mean state, air‐sea coupling does not substantially alter the MJO in SPCAM3, in contrast to previous studies. When constrained to the SPCCSM ocean mean state, SPCAM3‐KPP fails to produce an MJO, in stark contrast to the strong MJO in SPCCSM3. Further KPP simulations demonstrate that the MJO in SPCCSM3 arises from an overly strong sensitivity to El Niño–Southern Oscillation events. Our results show that simulated interannual variability and coupled‐model mean state biases affect the perceived response of the MJO to coupling. This is particularly concerning in the context of internal variability in coupled models, as many previous MJO sensitivity studies in coupled models used relatively short (20‐ to 50‐year) simulations that undersample interannual‐decadal variability. Diagnosing the effects of coupling on the MJO requires simulations that carefully control for mean state biases and interannual variability.
YTHDF2 promotes spermagonial adhesion through modulating MMPs decay via m6A/mRNA pathway
Authors: Huang Tao , Liu Zidong , Zheng Yi , Feng Tongying , Gao Qiang , Zeng Wenxian
Published: January 2020

As the foundation of male fertility, spermatogenesis is a complicated and highly controlled process. YTHDF2 plays regulatory roles in biological processes through accelerating the degradation of target mRNAs. However, the function of YTHDF2 in spermatogenesis remains elusive. Here, we knocked out Ythdf2 in mouse spermatogonia via CRISPR/Cas9, and found that depletion of Ythdf2 mainly downregulated the expression of matrix metallopeptidase (MMPs), thus affecting cell adhesion and proliferation. m6A-IP-PCR and RIP-PCR analysis showed that Mmp3, Mmp13, Adamts1 and Adamts9 were modified with m6A and simultaneously interacted with YTHDF2. Moreover, inhibition of Mmp13 partially rescued the phenotypes in Ythdf2-KO cells. Taken together, YTHDF2 regulates cell-matrix adhesion and proliferation through modulating the expression of Mmps by the m6A/mRNA degradation pathway.
Efficient base editing with high precision in rabbits using YFE-BE4max
Authors: Liu Zhiquan , Chen Siyu , Shan Huanhuan , Jia Yingqi , Chen Mao , Song Yuning , Lai Liangxue , Li Zhanjun
Published: January 2020

Cytidine base editors, composed of a cytidine deaminase fused to Cas9 nickase, enable efficient C-to-T conversion in various organisms. However, current base editors suffer from severe trade-off between editing efficiency and precision. Here, based on rationally mutated cytidine deaminase domain, we develop a new base editor, YFE-BE4max, effectively narrow the editing width to as little as approximately three nucleotides while maintaining high efficiency in rabbits. Moreover, YFE-BE4max successfully mediated the Tyr p. Q68Stop and Lmna p. G607G mutation in F0 rabbit with high efficiency and precision, which precisely recapitulates the pathological features of human OCA1 and HGPS, respectively. Collectively, YFE-BE4max system provide promising tools to perform efficient base editing with high precision in rabbits and enhances its capacity to precisely model human diseases.
Antarctic Ice Sheet and emission scenario controls on 21st-century extreme sea-level changes
Authors: Frederikse Thomas , Buchanan Maya K. , Lambert Erwin , Kopp Robert E. , Oppenheimer Michael , Rasmussen D. J. , Wal Roderik S. W. van de
Published: January 2020

Uncertainties in Representative Concentration Pathway (RCP) scenarios and Antarctic Ice Sheet (AIS) melt propagate into uncertainties in projected mean sea-level (MSL) changes and extreme sea-level (ESL) events. Here we quantify the impact of RCP scenarios and AIS contributions on 21st-century ESL changes at tide-gauge sites across the globe using extreme-value statistics. We find that even under RCP2.6, almost half of the sites could be exposed annually to a present-day 100-year ESL event by 2050. Most tropical sites face large increases in ESL events earlier and for scenarios with smaller MSL changes than extratropical sites. Strong emission reductions lower the probability of large ESL changes but due to AIS uncertainties, cannot fully eliminate the probability that large increases in frequencies of ESL events will occur. Under RCP8.5 and rapid AIS mass loss, many tropical sites, including low-lying islands face a MSL rise by 2100 that exceeds the present-day 100-year event level.
Unveiling the Re effect in Ni-based single crystal superalloys
Authors: Wu Xiaoxiang , Makineni Surendra Kumar , Liebscher Christian H. , Dehm Gerhard , Rezaei Mianroodi Jaber , Shanthraj Pratheek , Svendsen Bob , Bürger David , Eggeler Gunther , Raabe Dierk , Gault Baptiste
Published: January 2020

Single crystal Ni-based superalloys have long been an essential material for gas turbines in aero engines and power plants due to their outstanding high temperature creep, fatigue and oxidation resistance. A turning point was the addition of only 3 wt.% Re in the second generation of single crystal Ni-based superalloys which almost doubled the creep lifetime. Despite the significance of this improvement, the mechanisms underlying the so-called “Re effect” have remained controversial. Here, we provide direct evidence of Re enrichment to crystalline defects formed during creep deformation, using combined transmission electron microscopy, atom probe tomography and phase field modelling. We reveal that Re enriches to partial dislocations and imposes a drag effect on dislocation movement, thus reducing the creep strain rate and thereby improving creep properties. These insights can guide design of better superalloys, a quest which is key to reducing CO2 emissions in air-traffic.
Scalable photonic sources using two-dimensional lead halide perovskite superlattices
Authors: Jagielski Jakub , Solari Simon F. , Jordan Lucie , Scullion Declan , Blülle Balthasar , Li Yen-Ting , Krumeich Frank , Chiu Yu-Cheng , Ruhstaller Beat , Santos Elton J. G. , Shih Chih-Jen
Published: January 2020

Miniaturized photonic sources based on semiconducting two-dimensional (2D) materials offer new technological opportunities beyond the modern III-V platforms. For example, the quantum-confined 2D electronic structure aligns the exciton transition dipole moment parallel to the surface plane, thereby outcoupling more light to air which gives rise to high-efficiency quantum optics and electroluminescent devices. It requires scalable materials and processes to create the decoupled multi-quantum-well superlattices, in which individual 2D material layers are isolated by atomically thin quantum barriers. Here, we report decoupled multi-quantum-well superlattices comprised of the colloidal quantum wells of lead halide perovskites, with unprecedentedly ultrathin quantum barriers that screen interlayer interactions within the range of 6.5 Å. Crystallographic and 2Dk-space spectroscopic analysis reveals that the transition dipole moment orientation of bright excitons in the superlattices is predominantly in-plane and independent of stacking layer and quantum barrier thickness, confirming interlayer decoupling.
Phenotypic changes of HER2-positive breast cancer during and after dual HER2 blockade
Authors: Brasó-Maristany Fara , Griguolo Gaia , Pascual Tomás , Paré Laia , Nuciforo Paolo , Llombart-Cussac Antonio , Bermejo Begoña , Oliveira Mafalda , Morales Serafín , Martínez Noelia , Vidal Maria , Adamo Barbara , Martínez Olga , Pernas Sonia , López Rafael , Muñoz Montserrat , Chic Núria , Galván Patricia , Garau Isabel , Manso Luis , Alarcón Jesús , Martínez Eduardo , Gregorio Sara , Gomis Roger R. , Villagrasa Patricia , Cortés Javier , Ciruelos Eva , Prat Aleix
Published: January 2020

The HER2-enriched (HER2-E) subtype within HER2-positive (HER2+) breast cancer is highly addicted to the HER2 pathway. However, ∼20–60% of HER2+/HER2-E tumors do not achieve a complete response following anti-HER2 therapies. Here we evaluate gene expression data before, during and after neoadjuvant treatment with lapatinib and trastuzumab in HER2+/HER2-E tumors of the PAMELA trial and breast cancer cell lines. Our results reveal that dual HER2 blockade in HER2-E disease induces a low-proliferative Luminal A phenotype both in patient’s tumors and in vitro models. These biological changes are more evident in hormone receptor-positive (HR+) disease compared to HR-negative disease. Interestingly, increasing the luminal phenotype with anti-HER2 therapy increased sensitivity to CDK4/6 inhibition. Finally, discontinuation of HER2-targeted therapy in vitro, or acquired resistance to anti-HER2 therapy, leads to restoration of the original HER2-E phenotype. Our findings support the use of maintenance anti-HER2 therapy and the therapeutic exploitation of subtype switching with CDK4/6 inhibition.
Androgen deprivation upregulates SPINK1 expression and potentiates cellular plasticity in prostate cancer
Authors: Tiwari Ritika , Manzar Nishat , Bhatia Vipul , Yadav Anjali , Nengroo Mushtaq A. , Datta Dipak , Carskadon Shannon , Gupta Nilesh , Sigouros Michael , Khani Francesca , Poutanen Matti , Zoubeidi Amina , Beltran Himisha , Palanisamy Nallasivam , Ateeq Bushra
Published: January 2020

Emergence of an aggressive androgen receptor (AR)-independent neuroendocrine prostate cancer (NEPC) after androgen-deprivation therapy (ADT) is well-known. Nevertheless, the majority of advanced-stage prostate cancer patients, including those with SPINK1-positive subtype, are treated with AR-antagonists. Here, we show AR and its corepressor, REST, function as transcriptional-repressors of SPINK1, and AR-antagonists alleviate this repression leading to SPINK1 upregulation. Increased SOX2 expression during NE-transdifferentiation transactivates SPINK1, a critical-player for maintenance of NE-phenotype. SPINK1 elicits epithelial-mesenchymal-transition, stemness and cellular-plasticity. Conversely, pharmacological Casein Kinase-1 inhibition stabilizes REST, which in cooperation with AR causes SPINK1 transcriptional-repression and impedes SPINK1-mediated oncogenesis. Elevated levels of SPINK1 and NEPC markers are observed in the tumors of AR-antagonists treated mice, and in a subset of NEPC patients, implicating a plausible role of SPINK1 in treatment-related NEPC. Collectively, our findings provide an explanation for the paradoxical clinical-outcomes after ADT, possibly due to SPINK1 upregulation, and offers a strategy for adjuvant therapies.
Encapsulation mechanisms and structural studies of GRM2 bacterial microcompartment particles
Authors: Kalnins Gints , Cesle Eva-Emilija , Jansons Juris , Liepins Janis , Filimonenko Anatolij , Tars Kaspars
Published: January 2020

Bacterial microcompartments (BMCs) are prokaryotic organelles consisting of a protein shell and an encapsulated enzymatic core. BMCs are involved in several biochemical processes, such as choline, glycerol and ethanolamine degradation and carbon fixation. Since non-native enzymes can also be encapsulated in BMCs, an improved understanding of BMC shell assembly and encapsulation processes could be useful for synthetic biology applications. Here we report the isolation and recombinant expression of BMC structural genes from theKlebsiella pneumoniaeGRM2 locus, the investigation of mechanisms behind encapsulation of the core enzymes, and the characterization of shell particles by cryo-EM. We conclude that the enzymatic core is encapsulated in a hierarchical manner and that the CutC choline lyase may play a secondary role as an adaptor protein. We also present a cryo-EM structure of a pT = 4 quasi-symmetric icosahedral shell particle at 3.3 Å resolution, and demonstrate variability among the minor shell forms.
High-resolution and bias-corrected CMIP5 projections for climate change impact assessments
Authors: Navarro-Racines Carlos , Tarapues Jaime , Thornton Philip , Jarvis Andy , Ramirez-Villegas Julian
Published: January 2020

Projections of climate change are available at coarse scales (70–400 km). But agricultural and species models typically require finer scale climate data to model climate change impacts. Here, we present a global database of future climates developed by applying the delta method –a method for climate model bias correction. We performed a technical evaluation of the bias-correction method using a ‘perfect sibling’ framework and show that it reduces climate model bias by 50–70%. The data include monthly maximum and minimum temperatures and monthly total precipitation, and a set of bioclimatic indices, and can be used for assessing impacts of climate change on agriculture and biodiversity. The data are publicly available in the World Data Center for Climate (WDCC; cera-www.dkrz.de), as well as in the CCAFS-Climate data portal (http://ccafs-climate.org). The database has been used up to date in more than 350 studies of ecosystem and agricultural impact assessment.
Metabolomic and Lipidomic Signatures of Metabolic Syndrome and its Physiological Components in Adults: A Systematic Review
Authors: Monnerie Stéphanie , Comte Blandine , Ziegler Daniela , Morais José A. , Pujos-Guillot Estelle , Gaudreau Pierrette
Published: January 2020

The aim of this work was to conduct a systematic review of human studies on metabolite/lipid biomarkers of metabolic syndrome (MetS) and its components, and provide recommendations for future studies. The search was performed in MEDLINE, EMBASE, EMB Review, CINHAL Complete, PubMed, and on grey literature, for population studies identifying MetS biomarkers from metabolomics/lipidomics. Extracted data included population, design, number of subjects, sex/gender, clinical characteristics and main outcome. Data were collected regarding biological samples, analytical methods, and statistics. Metabolites were compiled by biochemical families including listings of their significant modulations. Finally, results from the different studies were compared. The search yielded 31 eligible studies (2005–2019). A first category of articles identified prevalent and incident MetS biomarkers using mainly targeted metabolomics. Even though the population characteristics were quite homogeneous, results were difficult to compare in terms of modulated metabolites because of the lack of methodological standardization. A second category, focusing on MetS components, allowed comparing more than 300 metabolites, mainly associated with the glycemic component. Finally, this review included also publications studying type 2 diabetes as a whole set of metabolic risks, raising the interest of reporting metabolomics/lipidomics signatures to reflect the metabolic phenotypic spectrum in systems approaches.
STF-62247 and pimozide induce autophagy and autophagic cell death in mouse embryonic fibroblasts
Authors: Kinzler Maximilian N. , Zielke Svenja , Kardo Simon , Meyer Nina , Kögel Donat , van Wijk Sjoerd J. L. , Fulda Simone
Published: January 2020

Induction of autophagy can have beneficial effects in several human diseases, e.g. cancer and neurodegenerative diseases (ND). Here, we therefore evaluated the potential of two novel autophagy-inducing compounds, i.e. STF-62247 and pimozide, to stimulate autophagy as well as autophagic cell death (ACD) using mouse embryonic fibroblasts (MEFs) as a cellular model. Importantly, both STF-62247 and pimozide triggered several hallmarks of autophagy in MEFs, i.e. enhanced levels of LC3B-II protein, its accumulation at distinct cytosolic sites and increase of the autophagic flux. Intriguingly, autophagy induction by STF-62247 and pimozide resulted in cell death that was significantly reduced in ATG5- or ATG7-deficient MEFs. Consistent with ACD induction, pharmacological inhibitors of apoptosis, necroptosis or ferroptosis failed to protect MEFs from STF-62247- or pimozide-triggered cell death. Interestingly, at subtoxic concentrations, pimozide stimulated fragmentation of the mitochondrial network, degradation of mitochondrial proteins (i.e. mitofusin-2 and cytochrome c oxidase IV (COXIV)) as well as a decrease of the mitochondrial mass, indicative of autophagic degradation of mitochondria by pimozide. In conclusion, this study provides novel insights into the induction of selective autophagy as well as ACD by STF-62247 and pimozide in MEFs.
Information transfer through food from parents to offspring in wild Javan gibbons
Authors: Yi Yoonjung , Kim Yena , Hikmat Agus , Choe Jae C.
Published: January 2020

The adaptive functions of food transfer from parents to their offspring have been explained mainly by two mutually non-exclusive hypotheses: the nutritional and informational hypotheses. In this study, we examined the functions of food transfer in wild Javan gibbons (Hylobates moloch) by testing these hypotheses from both infants’ and mothers’ perspectives. We observed 83 cases of food solicitations that resulted in 54 occasions of food transfers in three groups over a 19-month period in Gunung Halimun-Salak National Park, Indonesia. Infants initiated all solicitations directed at their mothers with one solicitation towards a father. Food solicitation rate decreased as infant age increased and ceased before weaning. As predicted by the informational hypothesis, infants solicited more food items difficult to obtain and preferred by their parents. On the contrary to the nutritional hypothesis, infants solicited low-quality items more often than high-quality items. Mothers did not change probability of food transfer according to the food characteristics or infant age. Hence, our results suggest that the primary function of food transfer from mother to infant Javan gibbons seems to be information transfer rather than nutritional aids, similarly to great apes.
The evolutionary diversity of locomotor innovation in rodents is not linked to proximal limb morphology
Authors: Hedrick Brandon P. , Dickson Blake V. , Dumont Elizabeth R. , Pierce Stephanie E.
Published: January 2020

Rodents are the most species-rich order within Mammalia and have evolved disparate morphologies to accommodate numerous locomotor niches, providing an excellent opportunity to understand how locomotor innovation can drive speciation. To evaluate the connection between the evolutionary success of rodents and the diversity of rodent locomotor ecologies, we used a large dataset of proximal limb CT scans from across Myomorpha and Geomyoidea to examine internal and external limb shape. Only fossorial rodents displayed a major reworking of their proximal limbs in either internal or external morphology, with other locomotor modes plotting within a generalist morphospace. Fossorial rodents were also the only locomotor mode to consistently show increased rates of humerus/femur morphological evolution. We propose that these rodent clades were successful at spreading into ecological niches due to high behavioral plasticity and small body sizes, allowing them to modify their locomotor mode without requiring major changes to their proximal limb morphology.
Forecasting high-dimensional dynamics exploiting suboptimal embeddings
Authors: Okuno Shunya , Aihara Kazuyuki , Hirata Yoshito
Published: January 2020

Delay embedding—a method for reconstructing dynamical systems by delay coordinates—is widely used to forecast nonlinear time series as a model-free approach. When multivariate time series are observed, several existing frameworks can be applied to yield a single forecast combining multiple forecasts derived from various embeddings. However, the performance of these frameworks is not always satisfactory because they randomly select embeddings or use brute force and do not consider the diversity of the embeddings to combine. Herein, we develop a forecasting framework that overcomes these existing problems. The framework exploits various “suboptimal embeddings” obtained by minimizing the in-sample error via combinatorial optimization. The framework achieves the best results among existing frameworks for sample toy datasets and a real-world flood dataset. We show that the framework is applicable to a wide range of data lengths and dimensions. Therefore, the framework can be applied to various fields such as neuroscience, ecology, finance, fluid dynamics, weather, and disaster prevention.
Characterization of key bacterial species in the Daphnia magna microbiota using shotgun metagenomics
Authors: Cooper Reilly O. , Cressler Clayton E.
Published: January 2020

The keystone zooplankton Daphnia magna has recently been used as a model system for understanding host-microbiota interactions. However, the bacterial species present and functions associated with their genomes are not well understood. In order to understand potential functions of these species, we combined 16S rRNA sequencing and shotgun metagenomics to characterize the whole-organism microbiota of Daphnia magna. We assembled five potentially novel metagenome-assembled genomes (MAGs) of core bacteria in Daphnia magna. Genes involved in host colonization and immune system evasion were detected across the MAGs. Some metabolic pathways were specific to some MAGs, including sulfur oxidation, nitrate reduction, and flagellar assembly. Amino acid exporters were identified in MAGs identified as important for host fitness, and pathways for key vitamin biosynthesis and export were identified across MAGs. In total, our examination of functions in these MAGs shows a diversity of nutrient acquisition and metabolism pathways present that may benefit the host, as well as genomic signatures of host association and immune system evasion.
Investigation of fragmentation behaviours of isoquinoline alkaloids by mass spectrometry combined with computational chemistry
Authors: Qing Zhixing , Xu Yuqin , Yu Liuyi , Liu Jinghong , Huang Xiuqiong , Tang Zhaoshan , Cheng Pi , Zeng Jianguo
Published: January 2020

Isoquinoline alkaloids, which are one of the most important types of alkaloids, are extensively distributed in herbal medicines. However, systematic and comprehensive investigations of the fragmentation behaviours of isoquinoline alkaloids have rarely been reported. Therefore, the goal of the present study is to simultaneously investigate the collision-induced dissociation patterns and the corresponding mechanism of isoquinoline alkaloids by mass spectrometry (MS) combined with computations. Nineteen types of isoquinoline alkaloids (66 compounds) were used as references to identify the characteristic fragmentation behaviours by quadrupole time-of-flight mass spectrometry (Q-TOF/MS) in positive electrospray ionization (ESI) mode. These types of isoquinoline alkaloids were divided into three categories primarily by the characteristic [M-NHR1R2]+ (R1 and R2 represent the substituent groups of the N-atom) fragment ions. High- and low-abundance [M-NHR1R2]+ ions were observed respectively for type I (1–13) and type II (14–29) alkaloids, respectively; however, the characteristic fragments were not detected for type III alkaloids (30–66) because of the existence of a p-π conjugated system. Each type of alkaloid was further classified by its characteristic fragmentation patterns and fragment ions. In addition, isoquinoline alkaloid with vicinal methoxy and hydroxy, vicinal methoxy, methylenedioxy, methoxy, and quaternary N-methyl groups could form the characteristic fragments by the loss of CH3OH, CH4, CH2O or CO, CH3 and CO, and CH3 moieties, respectively. The mechanisms of some interesting fragmentation behaviours, such as the formation of [M-NH3]+ and [M-CH3]+ fragment ions, were further demonstrated by computational chemistry. These characteristic fragmentation behaviours and fragment ions of isoquinoline alkaloids provide a solid foundation for the rapid and high-efficiency structural elucidation of similar metabolites in plant-derived medicines.
1.27 kW, 2.2 GHz pseudo-random binary sequence phase modulated fiber amplifier with Brillouin gain-spectrum overlap
Authors: Liu Meizhong , Yang Yifeng , Shen Hui , Zhang Jingpu , Zou Xingxing , Wang Hanbin , Yuan Lucheng , You Yang , Bai Gang , He Bing , Zhou Jun
Published: January 2020

We present a 2.2 GHz modulated, 1.27 kW output power, monolithic fiber amplifier based on pseudo-random binary sequence (PRBS) phase modulation. The spectral line spacing of maximizing the threshold enhancement factor (plateau of trend) was found by theoretical simulation. The spectral line spacing was adjusted to 12.7 MHz by a pattern length of n = 9, which is close to the plateau of trend in the proposed architecture. A 2.2 GHz low-pass radio frequency filter was used to control the FWHM of the seed. A four-stage Yb-doped fiber amplifier chain was established to boost a distributed Bragg reflector (DBR) laser and a distributed feedback (DFB) diode laser to 1.2 kW and 1.27 kW with a backward reflectively of <1‰, which shows a good suppression of SBS effect.
Conformational changes in Apolipoprotein N-acyltransferase (Lnt)
Authors: Wiseman Benjamin , Högbom Martin
Published: January 2020

Lipoproteins are important components of the cell envelope and are responsible for many essential cellular functions. They are produced by the post-translational covalent attachment of lipids that occurs via a sequential 3-step process controlled by three integral membrane enzymes. The last step of this process, unique to Gram-negative bacteria, is the N-acylation of the terminal cysteine by Apolipoprotein N-acyltransferase (Lnt) to form the final mature lipoprotein. Here we report 2 crystal forms of Lnt from Escherichia coli. In one form we observe a highly dynamic arm that is able to restrict access to the active site as well as a covalent modification to the active site cysteine consistent with the thioester acyl-intermediate. In the second form, the enzyme crystallized in an open conformation exposing the active site to the environment. In total we observe 3 unique Lnt molecules that when taken together suggest the movement of essential loops and residues are triggered by substrate binding that could control the interaction between Lnt and the incoming substrate apolipoprotein. The results provide a dynamic context for residues shown to be central for Lnt function and provide further insights into its mechanism.
Green Reduction of Graphene Oxide using Kaffir Lime Peel Extract (Citrus hystrix) and Its Application as Adsorbent for Methylene Blue
Authors: Wijaya Ronald , Andersan Gracia , Permatasari Santoso Shella , Irawaty Wenny
Published: January 2020

Green reduction of graphene oxide (GO) by phytochemicals was explored using the aqueous extract of kaffir lime peels. The research methods included preparation of extracts, preparation of GO, preparation and characterization of reduced-GO (RGO) using Fourier Transform Infrared (FTIR), X-ray diffraction (XRD), and UV-Vis spectroscopy, as well as methylene blue (MB) adsorption test using RGO. The RGO characterization showed that GO was successfully reduced by a C=C group restoration. The MB adsorption kinetics profile in RGO is more suitable for the pseudo-second-order model, whereas for the adsorption isotherm it is more suitable for the Langmuir model with a maximum adsorption capacity (qmax) of 276.06 mg/g at room temperature. The best ratio of GO: kaffir lime peel extract used to prepare RGO was at a ratio of 1: 2. Based on the ΔG, ΔH, and ΔS values, the adsorption of RGO-MB was defined as spontaneous and endothermic process. The results promise the potential application of RGO derived via green route to remove cationic dye in wastewater.
Sampling and processing blood samples within the South American Youth/Child cARdiovascular and Environmental (SAYCARE) Study
Authors: López Graciela , Assali Serruya Raphael , Barchuk Magalí , Gaitan-Charry Diego , Torres-Leal Francisco Leonardo , Moreno Luis Alberto , Delgado Carlos Alberto , Barbosa Carvalho Heráclito , De Moraes Augusto César Ferreira , Berg Gabriela
Published: January 2020

Obesity and overweight in children and adolescents is increasing rapidly worldwide; however, scarce data have been reported from South America countries. With the purpose of assessing hyperlipidemia, insulin resistance and chronic inflammation, the evaluation of blood biomarkers such as glucose, lipoproteins and chronic inflammation proteins is required. In the context of the SAYCARE study, in children and adolescents (3 to 18 years) from seven South American cities, our aim was to assess the impact of pre analytical conditions on different biomarkers evaluated in 474 fresh serum samples, in different country centers. We also evaluated the stability according to time and frozen storage within this study across the concordance of the results obtained from the 49 blood samples measured in three different centers. Significant correlations as well as concordance were observed in TG, Total-C, HDL-C and glucose between Buenos Aires and São Paulo. The samples evaluated in Teresina and São Paulo presented similar results, with exception of total cholesterol. We observed acceptable concordance between Buenos Aires vs São Paulo and Teresina vs São Paulo, suggesting that samples could be processed in each of these centers. This concordance is a consequence of the strict pre analytical conditions previously established in the SAYCARE study.
Predicting Radiation Resistance in Breast Cancer with Expression Status of Phosphorylated S6K1
Authors: Choi Jihye , Yoon Yi Na , Kim Nawon , Park Chan Sub , Seol Hyesil , Park In-Chul , Kim Hyun-Ah , Noh Woo Chul , Kim Jae-Sung , Seong Min-Ki
Published: January 2020

Emerging evidence suggests that the mammalian target of rapamcyin (mTOR) pathway is associated with radio-resistance in cancer treatment. We hypothesised that phosphorylated ribosomal S6 kinase 1 (p-S6K1), a major downstream regulator of the mTOR pathway, may play a role in predicting radio-resistance. Therefore, we evaluated the association of p-S6K1 expression with radio-resistance in breast cancer cell lines and patients. During median follow-up of 33 (range, 0.1–111) months for 1770 primary breast cancer patients who underwent surgery, patients expressing p-S6K1 showed worse 10-year loco-regional recurrence-free survival (LRFS) compared to that of p-S6K1-negative patients after radiotherapy (93.4% vs. 97.7%, p = 0.015). Multivariate analysis revealed p-S6K1 expression as a predictor of radio-resistance (hazard ratio 7.9, 95% confidence interval 1.1–58.5, p = 0.04). In vitro, CD44high/CD24low MCF7 cells with a radioresistant phenotype expressed higher levels of p-S6K1 than control MCF7 cells. Furthermore, the combination of radiation with treatment of everolimus, an mTOR-S6K1 pathway inhibitor, sensitised CD44high/CD24low MCF7 cells to a greater extent than MCF7 cells. This study provides in vivo and in vitro evidence for p-S6K1 expression status as an important marker for predicting the resistance to radiotherapy and as a possible target for radio-sensitization in breast cancer patients.
Novel invasion indices quantify the feed-forward facilitation of tumor invasion by macrophages
Authors: Lim Gippeum J. , Kang Suk-Jo , Lee Ji Youn
Published: January 2020

Quantitative and reliable measurement of cellular invasion is important to understand a range of biological processes such as cancer metastasis and angiogenesis. Spheroid invasion assays are an attractive in vitro platform because they effectively mimic the tumor cell invasion of solid tissues. Here, we developed an image analysis–based method to quantify the invasiveness of HT1080 human fibrosarcoma tumor cell spheroids. We segmented a cell-covered area into three subareas using objectively set threshold pixel intensities and calculated invasion indices using these subareas. Comparison with conventional parameters for spheroid invasion assays, such as area, length, and detached cells, showed that our indices present the invasion event at an early time and without being convoluted by proliferation. As an application, we then examined paracrine interactions between LLC1 mouse lung carcinoma cells and Raw264.7 mouse macrophage cells with our developed analysis method. We found that the invasion of tumor spheroids was increased by a macrophage-conditioned medium, concomitantly with a decrease in tumor cell proliferation. Importantly, invasion was further enhanced by a conditioned medium from activated macrophages by co-culture with tumor cells. Thus, our indices reveal that tumor cell invasion is facilitated in a feed-forward manner by communication between tumor cells and macrophages in the tumor microenvironment.
TAK-242 ameliorates contact dermatitis exacerbated by IL-36 receptor antagonist deficiency
Authors: Fukushima Hidehiko , Iwata Yohei , Watanabe Soichiro , Saito Kenta , Tanaka Yoshihito , Hasegawa Yurie , Akiyama Masashi , Sugiura Kazumitsu
Published: January 2020

Loss-of-function mutations in IL36RN cause generalized pustular psoriasis (GPP), which is characterized by neutrophil-infiltrated lesions. Neutrophils are important during contact hypersensitivity in mice. However, it has never been determined whether interleukin-36 receptor antagonist (IL-36Ra) deficiency is an exacerbating factor in contact dermatitis. We examined whether a loss-of-function IL36RN mutation exacerbates contact dermatitis and evaluated the changes in contact dermatitis-related cytokines. Wild-type and Il36rn−/− mice were treated with 1-fluoro-2,4-dinitorobenzene (DNFB) and evaluated for ear thickness, histopathological features, numbers of infiltrated neutrophils, and numbers of CD4 + and CD8 + T cells. Furthermore, mRNA levels of contact dermatitis-related cytokines were measured by real-time polymerase chain reaction, and effects of TAK-242, a toll-like receptor 4 (TLR4) inhibitor, on the contact hypersensitivity (CHS) response were evaluated. We found that the ear thickness, cytokine expression, and neutrophil infiltration significantly increased in Il36rn−/− mice compared with that in wild-type mice. TAK-242 alleviated CHS and prevented neutrophil infiltration, cytokine expression, and ear thickening in Il36rn−/− mice. These data indicate that Il36rn−/− mutations are an exacerbating factor for CHS and that TAK-242 can reduce the inflammatory responses that are associated with the CHS response.
Property Variation in Wavelength-thick Epsilon-Near-Zero ITO Metafilm for Near IR Photonic Devices
Authors: Ni Jimmy H. , Sarney Wendy L. , Leff Asher C. , Cahill James P. , Zhou Weimin
Published: January 2020

Thin indium tin oxide (ITO) films have been used as a medium to investigate epsilon-near-zero (ENZ) behavior for unconventional tailoring and manipulation of the light-matter interaction. However, the ENZ wavelength regime has not been studied carefully for ITO films with thicknesses larger than the wavelength. Thick ENZ ITO film would enable the development of a new family of ENZ-based opto-electronic devices that take full advantage of the ENZ behavior. Here, we demonstrated wavelength-thick ITO films reaching the ENZ regime around a wavelength of 1550 nm, which permit the design of such devices operating in the common optical telecommunications wavelength band. We discovered that the permittivity of the film was non-uniform with respect to the growth direction. In particular, after annealing at a sufficiently high temperature, the real part of the permittivity showed a step change from negative to positive value, crossing zero permittivity near the middle of the film. Subsequently, we conducted comprehensive microanalysis with X-ray diffraction, transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDS) to investigate the correlation of the permittivity variation with variations in the ITO crystallite morphology and relative concentrations of different atom species. The result of this study will allow us to design a new family of opto-electronic devices where ITO can be used as the cladding that guides light within an air-core waveguide to provide a new platform to explore ENZ properties such as environment insensitivity, super-coupling, and surface avoidance. We have also provided a comprehensive method to determine the permittivity in a non-uniform ENZ material by using an advanced physical model to the fit experimental data.
The role of Human leukocyte antigen class I on patient survival in Gastrointestinal cancers: a systematic review and meta- analysis
Authors: Najafimehr Hadis , Hajizadeh Nastaran , Nazemalhosseini-Mojarad Ehsan , Pourhoseingholi Mohamad Amin , Abdollahpour-Alitappeh Meghdad , Ashtari Sara , Zali Mohammad Reza
Published: January 2020

The prognostic role of Human leukocyte antigen class I (HLA- I) in gastrointestinal cancers has been remained controversial. We performed a meta-analysis to determine the role of classical HLA-I in predicting survival of patients. In addition, the relationship between HLA- I and some clinicopathological factors was evaluated. Published studies investigated HLA-I expression effect on gastrointestinal cancers were evaluated to determine association between HLA- I and overall survival (OS) and recurrence-free survival (RFS) in patients. The used effect sizes were hazard ratio (HR) and Odds ratio (OR) with 95% confidence interval (CI). A total of ten studies included 1307 patients were analyzed. The pooled results revealed that HLA- I overexpression was positively related to OS (HR: 0.72; 95% CI: 0.53–0.96) and demonstrated little association for RFS (HR: 0.70; 95% CI: 0.46–1.08). HLA-I overexpression is negative associated with poorer differentiation of tumor (OR: 0.53; 95% CI (0.43–0.81) and also higher stages of cancer (OR: 0.29; 95% CI (0.13–0.64). HLA- I overexpression was related to a better prognosis on OS and probably had little impact on RFS.
The Asthma-associated PER1-like domain-containing protein 1 (PERLD1) Haplotype Influences Soluble Glycosylphosphatidylinositol Anchor Protein (sGPI-AP) Levels in Serum and Immune Cell Proliferation
Authors: Sio Yang Yie , Anantharaman Ramani , Lee Sean Qiu En , Matta Sri Anusha , Ng Yu Ting , Chew Fook Tim
Published: January 2020

Post-glycosylphosphatidylinositol (GPI) attachment to proteins 3, also known as PGAP3 or PERLD1 (PER1-like domain-containing protein 1), participates in the lipid remodeling process of glycosylphosphatidylinositol (GPI) anchor proteins during post-translational modification. Functional defect in PERLD1 was previously hypothesized to influence this process in T-cells and their subsequent activation and proliferation. This current study aims to functionally characterize PERLD1 genetic variants and relate this with human immune cells proliferation rate upon stimulation. We first showed the association between a PERLD1 tag-single nucleotide polymorphism (tagSNP), rs2941504, and the development of asthma in our study population. This association remained significant after conditioning for the other asthma-associated SNP rs8076131 that is also located within the 17q12–21 region. Subsequent sequencing of 40 unrelated Singapore Chinese individuals identified 12 more common PERLD1 SNPs (minor allele frequency > 5%) that are in linkage disequilibrium (LD, r2 > 0.8) with rs2941504. Through in vitro studies, 7 of these SNPs were found to form a functional haplotype that influences alternative splicing of PERLD1 transcript. This result was validated in human peripheral blood mononuclear cell (PBMC), where the minor haplotype (Hap2) was shown to be associated with significantly increased PERLD1 truncated transcript. Additionally, Hap2 was found to be related to increased levels of several soluble GPI-anchored proteins (such as sCD55 and sCD59) in serum. Elevated sCD55 in the serum was demonstrated to reduce the proliferation rate of PBMCs upon phytohaemagglutinin (PHA) stimulation. Taken together, the current study has shown a functional PERLD1 haplotype, which modifies PBMC sensitivity upon stimulation and may contribute to the individual’s susceptibility to allergic asthma.