bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revisiting the Australian‐Antarctic Ocean‐Continent Transition Zone Using Petrological and Geophysical Characterization of Exhumed Subcontinental Mantle
Authors: McCarthy A. , Falloon T. J. , Sauermilch I. , Whittaker J. M. , Niida K. , Green D. H. 
Published: June 2020

AbstractThe final lithospheric breakup of the Australian‐Antarctic rift system remains controversial due to sparse geological constraints on the nature of the basement along the ocean‐continent transition (OCT) zones. We present new interpretations of multichannel seismic reflection transects and new petrological data of dredged mantle rocks along the East Antarctic margin (Seamount B, offshore Terre Adélie). By combining both data sets, we show that a 50–100 km wide domain of cold and fertile subcontinental mantle was exhumed along the magma‐poor Antarctic margin. This study represents only the second locality, along with the Iberia‐Newfoundland margins, where the importance of exhumed mantle domains along OCTs can be clearly identified. The dredged peridotites preserve characteristics similar to mantle xenoliths found in syn‐ to post‐rift volcanism at the eastern end of the Australian margin (Victoria and Tasmania), indicating the exhumation of fertile subcontinental mantle during rifting between Australia and Antarctica. Seamount B represents the initial stages of exhumation of cold subcontinental lithosphere along an OCT during rifting. This thick mantle domain was likely affected by melt impregnation at high pressure (8 kbar), leading to the formation of plagioclase‐pyroxenites. The combination of continental rifted blocks, a wide domain of volcanic‐poor subcontinental mantle and (ultra‐) slow spreading is analogous to OCTs from the Jurassic Western Tethys and Iberia‐Newfoundland rifted margins. Additionally, evidence of melt stagnation at high pressure suggests that magmatism along the Australian‐Antarctic rifted margins was sufficient to form magnetic anomalies that can be used as isochrons despite their formation in lithosphere other than mature, steady‐state ocean crust.
Time trends in pregnancy-related outcomes among women with type 1 diabetes mellitus, 2004–2017
Authors: Helman Sarit , James-Todd Tamarra M. , Wang Zifan , Bellavia Andrea , Wyckoff Jennifer A. , Serdy Shanti , Halprin Elizabeth , O’Brien Karen , Takoudes Tamara , Gupta Munish , McElrath Thomas F. , Brown Florence M. 
Published: June 2020

Abstract
Objective
To examine time trends in US pregnant women with type 1 diabetes mellitus for maternal characteristics and pregnancy outcomes.

Study design
We abstracted clinical data from the medical records of 700 pregnant women from 2004 to 2017. For each time period, means and percentages were calculated. P values for trend were calculated using linear and logistic regression.

Results
HbA1c in each trimester was unchanged across the analysis period. The prevalence of nephropathy decreased from 4.8% to 0% (P = 0.002). Excessive gestational weight gain increased (P = 0.01). Gestation length also increased (P = 0.01), as did vaginal deliveries (P = 0.03). There were no change in birthweight over time (P = 0.07) and the percentage of neonates with macrosomia and large for gestational age (LGA) neonates also remained unchanged.

Conclusion
Obstetric guideline changes may have improved gestation length and mode of delivery; however, other outcomes need more attention, including excessive gestational weight gain, macrosomia, and LGA.
Phase 2 study of cabazitaxel as second-line treatment in patients with HER2-negative metastatic breast cancer previously treated with taxanes—a Hellenic Cooperative Oncology Group (HeCOG) Trial
Authors: Koutras Angelos , Zagouri Flora , Koliou Georgia-Angeliki , Psoma Elizabeth , Chryssogonidis Ioannis , Lazaridis Georgios , Tryfonopoulos Dimitrios , Kotsakis Athanasios , Res Eleni , Kentepozidis Nikolaos K. , Razis Evangelia , Psyrri Amanda , Koumakis Georgios , Kalofonos Haralabos P. , Dimopoulos Meletios A. , Fountzilas George 
Published: June 2020

Abstract
Background
Cabazitaxel is a novel taxane that might be active in breast cancer resistant to first-generation taxanes.

Methods
The purpose of the current multicentre phase II trial was to evaluate the activity and safety of cabazitaxel, as second-line treatment, in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) previously treated with taxanes. The primary endpoint was objective response rate (ORR).

Results
Eighty-four patients were enrolled between October 2012 and November 2016. Taxane resistance to previous treatment was detected in 43 cases. The ORR was 22.6% in the intent-to-treat population, 23.3% in taxane-resistant and 20.5% in taxane-non-resistant cases. At a median follow-up of 39.6 months, the median progression-free survival and overall survival were 3.7 months (95% CI 2.2–4.4) and 15.2 months (95% CI 11.3–19.4), respectively. Regarding toxicity, grade 3–4 neutropenia was reported in 22.6% and febrile neutropenia in 6% of the patients, respectively. Two fatal events (one febrile neutropenia and one sepsis) were reported as being related to study treatment.

Conclusions
This phase II trial suggests that cabazitaxel is active as second-line treatment in taxane-pretreated patients with HER2-negative MBC, with manageable toxicity.
Characterization of a new small-molecule inhibitor of HDAC6 in glioblastoma
Authors: Auzmendi-Iriarte Jaione , Saenz-Antoñanzas Ander , Mikelez-Alonso Idoia , Carrasco-Garcia Estefania , Tellaetxe-Abete Maitena , Lawrie Charles H. , Sampron Nicolás , Cortajarena Aitziber L. , Matheu Ander 
Published: June 2020

AbstractHistone deacetylase 6 (HDAC6) is an epigenetic modifier that is an attractive pharmacological target in cancer. In this work, we show that HDAC6 is elevated in glioblastoma, the most malignant and common brain tumor in adults, in which its high levels correlate with poor patient survival and is more abundant in glioma stem cell subpopulation. Moreover, we identified a new small-molecule inhibitor of HDAC6, which presents strong sensitivity for HDAC6 inhibition and exerts high cytotoxic activity, alone or in combination with temozolomide. It is also able to significantly reduce tumor growth in vivo. Transcriptomic analysis of patient-derived glioma stem cells revealed an increase in cell differentiation and cell death pathways, as well as a decrease in cell-cycle activity and cell division by the treatment with the compound. Finally, the comparison with a pan-HDAC inhibitor, Vorinostat (SAHA), or HDAC6-specific inhibitor, Tubastatin A, showed higher target specificity and antitumor activity of the new HDAC6 inhibitor. In conclusion, our data reveal the efficacy of a novel HDAC6 inhibitor in glioblastoma preclinical setting.
TNF-alpha-induced microglia activation requires miR-342: impact on NF-kB signaling and neurotoxicity
Authors: Brás João Paulo , Bravo Joana , Freitas Jaime , Barbosa Mário Adolfo , Santos Susana Gomes , Summavielle Teresa , Almeida Maria Inês 
Published: June 2020

AbstractGrowing evidences suggest that sustained neuroinflammation, caused by microglia overactivation, is implicated in the development and aggravation of several neurological and psychiatric disorders. In some pathological conditions, microglia produce increased levels of cytotoxic and inflammatory mediators, such as tumor necrosis factor alpha (TNF-α), which can reactivate microglia in a positive feedback mechanism. However, specific molecular mediators that can be effectively targeted to control TNF-α-mediated microglia overactivation, are yet to be uncovered. In this context, we aim to identify novel TNF-α-mediated micro(mi)RNAs and to dissect their roles in microglia activation, as well as to explore their impact on the cellular communication with neurons. A miRNA microarray, followed by RT-qPCR validation, was performed on TNF-α-stimulated primary rat microglia. Gain- and loss-of-function in vitro assays and proteomic analysis were used to dissect the role of miR-342 in microglia activation. Co-cultures of microglia with hippocampal neurons, using a microfluidic system, were performed to understand the impact on neurotoxicity. Stimulation of primary rat microglia with TNF-α led to an upregulation of Nos2, Tnf, and Il1b mRNAs. In addition, ph-NF-kB p65 levels were also increased. miRNA microarray analysis followed by RT-qPCR validation revealed that TNF-α stimulation induced the upregulation of miR-342. Interestingly, miR-342 overexpression in N9 microglia was sufficient to activate the NF-kB pathway by inhibiting BAG-1, leading to increased secretion of TNF-α and IL-1β. Conversely, miR-342 inhibition led to a strong decrease in the levels of these cytokines after TNF-α activation. In fact, both TNF-α-stimulated and miR-342-overexpressing microglia drastically affected neuron viability. Remarkably, increased levels of nitrites were detected in the supernatants of these co-cultures. Globally, our findings show that miR-342 is a crucial mediator of TNF-α-mediated microglia activation and a potential target to tackle microglia-driven neuroinflammation.
An encrusting kleptoparasite-host interaction from the early Cambrian
Authors: Zhang Zhifei , Strotz Luke C. , Topper Timothy P. , Chen Feiyang , Chen Yanlong , Liang Yue , Zhang Zhiliang , Skovsted Christian B. , Brock Glenn A. 
Published: June 2020

AbstractParasite–host systems are pervasive in nature but are extremely difficult to convincingly identify in the fossil record. Here we report quantitative evidence of parasitism in the form of a unique, enduring life association between tube-dwelling organisms encrusted to densely clustered shells of a monospecific organophosphatic brachiopod assemblage from the lower Cambrian (Stage 4) of South China. Brachiopods with encrusting tubes have decreased biomass (indicating reduced fitness) compared to individuals without tubes. The encrusting tubes orient tightly in vectors matching the laminar feeding currents of the host, suggesting kleptoparasitism. With no convincing parasite–host interactions known from the Ediacaran, this widespread sessile association reveals intimate parasite–host animal systems arose in early Cambrian benthic communities and their emergence may have played a key role in driving the evolutionary and ecological innovations associated with the Cambrian radiation.
A powder-metallurgy-based strategy toward three-dimensional graphene-like network for reinforcing copper matrix composites
Authors: Zhang Xiang , Xu Yixin , Wang Miaocao , Liu Enzuo , Zhao Naiqin , Shi Chunsheng , Lin Dong , Zhu Fulong , He Chunnian 
Published: June 2020

AbstractThree-dimensional graphene network is a promising structure for improving both the mechanical properties and functional capabilities of reinforced polymer and ceramic matrix composites. However, direct application in a metal matrix remains difficult due to the reason that wetting is usually unfavorable in the carbon/metal system. Here we report a powder-metallurgy based strategy to construct a three-dimensional continuous graphene network architecture in a copper matrix through thermal-stress-induced welding between graphene-like nanosheets grown on the surface of copper powders. The interpenetrating structural feature of the as-obtained composites not only promotes the interfacial shear stress to a high level and thus results in significantly enhanced load transfer strengthening and crack-bridging toughening simultaneously, but also constructs additional three-dimensional hyperchannels for electrical and thermal conductivity. Our approach offers a general way for manufacturing metal matrix composites with high overall performance.
Rapid range shifts and megafaunal extinctions associated with late Pleistocene climate change
Authors: Seersholm Frederik V. , Werndly Daniel J. , Grealy Alicia , Johnson Taryn , Keenan Early Erin M. , Lundelius Ernest L. , Winsborough Barbara , Farr Grayal Earle , Toomey Rickard , Hansen Anders J. , Shapiro Beth , Waters Michael R. , McDonald Gregory , Linderholm Anna , Stafford Thomas W. , Bunce Michael 
Published: June 2020

AbstractLarge-scale changes in global climate at the end of the Pleistocene significantly impacted ecosystems across North America. However, the pace and scale of biotic turnover in response to both the Younger Dryas cold period and subsequent Holocene rapid warming have been challenging to assess because of the scarcity of well dated fossil and pollen records that covers this period. Here we present an ancient DNA record from Hall’s Cave, Texas, that documents 100 vertebrate and 45 plant taxa from bulk fossils and sediment. We show that local plant and animal diversity dropped markedly during Younger Dryas cooling, but while plant diversity recovered in the early Holocene, animal diversity did not. Instead, five extant and nine extinct large bodied animals disappeared from the region at the end of the Pleistocene. Our findings suggest that climate change affected the local ecosystem in Texas over the Pleistocene-Holocene boundary, but climate change on its own may not explain the disappearance of the megafauna at the end of the Pleistocene.
Loss of the transcription factor MAFB limits β-cell derivation from human PSCs
Authors: Russell Ronan , Carnese Phichitpol P. , Hennings Thomas G. , Walker Emily M. , Russ Holger A. , Liu Jennifer S. , Giacometti Simone , Stein Roland , Hebrok Matthias 
Published: June 2020

AbstractNext generation sequencing studies have highlighted discrepancies in β-cells which exist between mice and men. Numerous reports have identified MAF BZIP Transcription Factor B (MAFB) to be present in human β-cells postnatally, while its expression is restricted to embryonic and neo-natal β-cells in mice. Using CRISPR/Cas9-mediated gene editing, coupled with endocrine cell differentiation strategies, we dissect the contribution of MAFB to β-cell development and function specifically in humans. Here we report that MAFB knockout hPSCs have normal pancreatic differentiation capacity up to the progenitor stage, but favor somatostatin- and pancreatic polypeptide–positive cells at the expense of insulin- and glucagon-producing cells during endocrine cell development. Our results describe a requirement for MAFB late in the human pancreatic developmental program and identify it as a distinguishing transcription factor within islet cell subtype specification. We propose that hPSCs represent a powerful tool to model human pancreatic endocrine development and associated disease pathophysiology.
Insights into catalysis and regulation of non-canonical ubiquitination and deubiquitination by bacterial deamidase effectors
Authors: Wang Yong , Zhan Qi , Wang Xinlu , Li Peipei , Liu Songqing , Gao Guangxia , Gao Pu 
Published: June 2020

AbstractThe bacterial effector MavC catalyzes non-canonical ubiquitination of host E2 enzyme UBE2N without engaging any of the conventional ubiquitination machinery, thereby abolishing UBE2N’s function in forming K63-linked ubiquitin (Ub) chains and dampening NF-кB signaling. We now report the structures of MavC in complex with conjugated UBE2N~Ub and an inhibitor protein Lpg2149, as well as the structure of its ortholog, MvcA, bound to Lpg2149. Recognition of UBE2N and Ub depends on several unique features of MavC, which explains the inability of MvcA to catalyze ubiquitination. Unexpectedly, MavC and MvcA also possess deubiquitinase activity against MavC-mediated ubiquitination, highlighting MavC as a unique enzyme possessing deamidation, ubiquitination, and deubiquitination activities. Further, Lpg2149 directly binds and inhibits both MavC and MvcA by disrupting the interactions between enzymes and Ub. These results provide detailed insights into catalysis and regulation of MavC-type enzymes and the molecular mechanisms of this non-canonical ubiquitination machinery.
Supernumerary B chromosomes of Aegilops speltoides undergo precise elimination in roots early in embryo development
Authors: Ruban Alevtina , Schmutzer Thomas , Wu Dan D. , Fuchs Joerg , Boudichevskaia Anastassia , Rubtsova Myroslava , Pistrick Klaus , Melzer Michael , Himmelbach Axel , Schubert Veit , Scholz Uwe , Houben Andreas 
Published: June 2020

AbstractNot necessarily all cells of an organism contain the same genome. Some eukaryotes exhibit dramatic differences between cells of different organs, resulting from programmed elimination of chromosomes or their fragments. Here, we present a detailed analysis of programmed B chromosome elimination in plants. Using goatgrass Aegilops speltoides as a model, we demonstrate that the elimination of B chromosomes is a strictly controlled and highly efficient root-specific process. At the onset of embryo differentiation B chromosomes undergo elimination in proto-root cells. Independent of centromere activity, B chromosomes demonstrate nondisjunction of chromatids and lagging in anaphase, leading to micronucleation. Chromatin structure and DNA replication differ between micronuclei and primary nuclei and degradation of micronucleated DNA is the final step of B chromosome elimination. This process might allow root tissues to survive the detrimental expression, or overexpression of B chromosome-located root-specific genes with paralogs located on standard chromosomes.
A flexible artificial intrinsic-synaptic tactile sensory organ
Authors: Lee Yu Rim , Trung Tran Quang , Hwang Byeong-Ung , Lee Nae-Eung 
Published: June 2020

AbstractImbuing bio-inspired sensory devices with intelligent functions of human sensory organs has been limited by challenges in emulating the preprocessing abilities of sensory organs such as reception, filtering, adaptation, and sensory memory at the device level itself. Merkel cells, which is a part of tactile sensory organs, form synapse-like connections with afferent neuron terminals referred to as Merkel cell-neurite complexes. Here, inspired by structure and intelligent functions of Merkel cell-neurite complexes, we report a flexible, artificial, intrinsic-synaptic tactile sensory organ that mimics synapse-like connections using an organic synaptic transistor with ferroelectric nanocomposite gate dielectric of barium titanate nanoparticles and poly(vinylidene fluoride-trifluoroethylene). Modulation of the post-synaptic current of the device induced by ferroelectric dipole switching due to triboelectric-capacitive coupling under finger touch allowed reception and slow adaptation. Modulation of synaptic weight by varying the nanocomposite composition of gate dielectric layer enabled tuning of filtering and sensory memory functions.
Visualizable detection of nanoscale objects using anti-symmetric excitation and non-resonance amplification
Authors: Zhu Jinlong , Udupa Aditi , Goddard Lynford L. 
Published: June 2020

AbstractWhy can we not see nanoscale objects under a light microscope? The textbook answers are that their relative signals are weak and their separation is smaller than Abbe’s resolution limit. Thus, significant effort has gone into developing ultraviolet imaging, oil and solid immersion objectives, nonlinear methods, fluorescence dyes, evanescent wave tailoring, and point-spread function engineering. In this work, we introduce a new optical sensing framework based on the concepts of electromagnetic canyons and non-resonance amplification, to directly view on a widefield microscope λ/31-scale (25-nm radius) objects in the near-field region of nanowire-based sensors across a 726-μm × 582-μm field of view. Our work provides a simple but highly efficient framework that can transform conventional diffraction-limited optical microscopes for nanoscale visualization. Given the ubiquity of microscopy and importance of visualizing viruses, molecules, nanoparticles, semiconductor defects, and other nanoscale objects, we believe our proposed framework will impact many science and engineering fields.
In-situ measurements of fabrication induced strain in diamond photonic-structures using intrinsic colour centres
Authors: Knauer Sebastian , Hadden John P. , Rarity John G. 
Published: June 2020

AbstractDiamond has established itself as an ideal material for photonics and optomechanics, due to its broad-band transparency and hardness. In addition, colour centres hosted within its lattice such as the nitrogen-vacancy (NV) centre, have become leading candidates for use in quantum information processing, and quantum sensors. The fabrication of nanoscale devices coupled to high quality NVs has been an outstanding challenge due to their sensitivity to magnetic, electric and strain fields within their local environment. In this work, we show how the NV centre’s ground state electron spin can be used as an embedded atomic-scale probe of the local strain caused by focused ion beam milling of nanoscale devices. This technique can thus be used to measure, and optimise material and device fabrication processes to allow diamond to reach its full potential.
Spermidine Enhanced Free Polyamine Levels and Expression of Polyamine Biosynthesis Enzyme Gene in Rice Spikelets under Heat Tolerance before Heading
Authors: Zhou Rong , Hu Qijuan , Pu Qiong , Chen Moxian , Zhu Xiuru , Gao Cong , Zhou Guixiang , Liu Lijun , Wang Zhiqing , Yang Jianchang , Zhang Jianhua , Cao Yunying 
Published: June 2020

AbstractHigh temperatures (HT) before heading strongly inhibit the development of spikelets in rice. Spermidine (Spd) can improve rice’s resistance to HT stress; however, the mechanism underlying this effect has not been elucidated. This study investigated several parameters, including yield, superoxide anion (O2.-), protective enzyme activities, and polyamine content, in a heat-sensitive genotype, Shuanggui 1. The yield and yield components decreased dramatically when subjected to HT stress, while this reduction could be partially recovered by exogenous Spd. Spd also slowed the generation rate of O2.- and increased protective enzyme, superoxide dismutase (SOD) and catalase (CAT) activities both under normal and high temperatures, which suggested that Spd may participate in the antioxidant system. Furthermore, genes involved in polyamine synthesis were analyzed. The results show that HT before heading significantly increased the expression of arginine decarboxylase OsADC1, Spd synthase OsSPDS1 and OsSPDS3 and had little effect on the expression of the S-adenosylmethionine decarboxylase OsSAMDC2 and ornithine decarboxylase OsODC1. In addition, exogenous Spd considerably reduced the expression of OsSAMDC2, OsSPDS1 and OsSPDS3 under HT but not the expression of OsADC1. The above mentioned results indicate that the exogenous Spd could help young rice spikelets to resist HT stress by reducing the expression of OsSAMDC2, OsSPDS1 and OsSPDS3, resulting in higher levels of endogenous Spd and Spm, which were also positively correlated with yield. In conclusion, the adverse effect of HT stress on young spikelets seems to be alleviated by increasing the amounts of Spd and Spm, which provides guidance for adaptation to heat stress during rice production.