bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interannual Variability of the Natal Pulse
Authors: Yamagami Yoko , Tozuka Tomoki , Qiu Bo 
Published: December 2019

AbstractSatellite altimetry data and high‐resolution model output are used to investigate the mechanism of interannual variations of the solitary meander in the Agulhas Current, called the Natal Pulse. It is shown that most of the Natal Pulses are triggered by anticyclonic eddies originating from the Southeast Madagascar Current (SEMC) and anticyclonic eddies of the Mozambique Channel are the secondary source. In addition to the barotropic conversion suggested by previous studies, the advection of eddy kinetic energy (EKE) plays a statistically significant role in the growth of the Natal Pulse. The number of anticyclonic eddies arriving at the Natal Bight largely explains the interannual variations in the Natal Pulse. The barotropic conversion from the SEMC, whose interannual variations are likely related to the remote wind forcing, is the main EKE source and corresponds well with the interannual variations of anticyclonic eddies generated off the southern coast of Madagascar. It is also shown that the interannual variations of the Natal Pulse are linked to large‐scale wind variability in the southern Indian Ocean.
Alkalinity in Tidal Tributaries of the Chesapeake Bay
Authors: Najjar Raymond G. , Herrmann Maria , Cintrón Del Valle Sebastián M. , Friedman Jaclyn R. , Friedrichs Marjorie A.M. , Harris Lora A. , Shadwick Elizabeth H. , Stets Edward G. , Woodland Ryan J. 
Published: December 2019

AbstractDespite the important role of alkalinity in estuarine carbon cycling, the seasonal and decadal variability of alkalinity, particularly within multiple tidal tributaries of the same estuary, is poorly understood. Here we analyze more than 25,000 alkalinity measurements, mostly from the 1980s and 1990s, in the major tidal tributaries of the Chesapeake Bay, a large, coastal‐plain estuary of eastern North America. The long‐term means of alkalinity in tidal‐fresh waters vary by a factor of 6 among seven tidal tributaries, reflecting the alkalinity of nontidal rivers draining to these estuaries. At 25 stations, mostly in the Potomac River Estuary, we find significant long‐term increasing trends that exceed the trends in the nontidal rivers upstream of those stations. Box model calculations in the Potomac River Estuary indicate that the main cause of the estuarine trends is a declining alkalinity sink. The magnitude of this sink is consistent with a simple model of calcification by the invasive bivalve Corbicula fluminea. More generally, in tidal tributaries fed by high‐alkalinity nontidal rivers, alkalinity is consumed, with sinks ranging from 8% to 27% of the upstream input. In contrast, tidal tributaries that are fed by low‐alkalinity nontidal rivers have sources of alkalinity amounting to 34% to 171% of the upstream input. For a single estuarine system, the Chesapeake Bay has diverse alkalinity dynamics and can thus serve as a laboratory for studying the numerous processes influencing alkalinity among the world's estuaries.
First 10 Months of TGF Observations by ASIM
Authors: Østgaard N. , Neubert T. , Reglero V. , Ullaland K. , Yang S. , Genov G. , Marisaldi M. , Mezentsev A. , Kochkin P. , Lehtinen N. , Sarria D. , Qureshi B. H. , Solberg A. , Maiorana C. , Albrechtsen K. , Budtz‐Jørgensen C. , Kuvvetli I. , Christiansen F. , Chanrion O. , Heumesser M. , Navarro‐Gonzalez J. , Connell P. , Eyles C. , Christian H. , Al‐nussirat S. 
Published: December 2019

AbstractThe Atmosphere‐Space Interactions Monitor (ASIM) was launched to the International Space Station on 2 April 2018. The ASIM payload consists of two main instruments, the Modular X‐ray and Gamma‐ray Sensor (MXGS) for imaging and spectral analysis of Terrestrial Gamma‐ray Flashes (TGFs) and the Modular Multi‐spectral Imaging Array for detection, imaging, and spectral analysis of Transient Luminous Events and lightning. ASIM is the first space mission designed for simultaneous observations of Transient Luminous Events, TGFs, and optical lightning. During the first 10 months of operation (2 June 2018 to 1 April 2019) the MXGS has observed 217 TGFs. In this paper we report several unprecedented measurements and new scientific results obtained by ASIM during this period: (1) simultaneous TGF observations by Fermi Gamma‐ray Burst Monitor and ASIM MXGS revealing the very good detection capability of ASIM MXGS and showing substructures in the TGF, (2) TGFs and Elves produced during the same lightning flash and even simultaneously have been observed, (3) first imaging of TGFs giving a unique source location, (4) strong statistical support for TGFs being produced during the upward propagation of a leader just before a large current pulse heats up the channel and emits a strong optical pulse, and (5) the t50 duration of TGFs observed from space is shorter than previously reported.
Chronic corticosterone administration induces negative valence and impairs positive valence behaviors in mice
Authors: Dieterich Andrew , Srivastava Prachi , Sharif Aitesam , Stech Karina , Floeder Joseph , Yohn Samantha E. , Samuels Benjamin A. 
Published: December 2019

AbstractBehavioral approaches utilizing rodents to study mood disorders have focused primarily on negative valence behaviors associated with potential threat (anxiety-related behaviors). However, for disorders such as depression, positive valence behaviors that assess reward processing may be more translationally valid and predictive of antidepressant treatment outcome. Chronic corticosterone (CORT) administration is a well-validated pharmacological stressor that increases avoidance in negative valence behaviors associated with anxiety1–4. However, whether chronic stress paradigms such as CORT administration also lead to deficits in positive valence behaviors remains unclear. We treated male C57BL/6J mice with chronic CORT and assessed both negative and positive valence behaviors. We found that CORT induced avoidance in the open field and NSF. Interestingly, CORT also impaired instrumental acquisition, reduced sensitivity to a devalued outcome, reduced breakpoint in progressive ratio, and impaired performance in probabilistic reversal learning. Taken together, these results demonstrate that chronic CORT administration at the same dosage both induces avoidance in negative valence behaviors associated with anxiety and impairs positive valence behaviors associated with reward processing. These data suggest that CORT administration is a useful experimental system for preclinical approaches to studying stress-induced mood disorders.
Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification
Authors: Hwang Charles , Marini Simone , Huber Amanda K. , Stepien David M. , Sorkin Michael , Loder Shawn , Pagani Chase A. , Li John , Visser Noelle D. , Vasquez Kaetlin , Garada Mohamed A. , Li Shuli , Xu Jiajia , Hsu Ching-Yun , Yu Paul B. , James Aaron W. , Mishina Yuji , Agarwal Shailesh , Li Jun , Levi Benjamin 
Published: December 2019

AbstractHeterotopic ossification (HO) is a debilitating condition characterized by the pathologic formation of ectopic bone. HO occurs commonly following orthopedic surgeries, burns, and neurologic injuries. While surgical excision may provide palliation, the procedure is often burdened with significant intra-operative blood loss due to a more robust contribution of blood supply to the pathologic bone than to native bone. Based on these clinical observations, we set out to examine the role of vascular signaling in HO. Vascular endothelial growth factor A (VEGFA) has previously been shown to be a crucial pro-angiogenic and pro-osteogenic cue during normal bone development and homeostasis. Our findings, using a validated mouse model of HO, demonstrate that HO lesions are highly vascular, and that VEGFA is critical to ectopic bone formation, despite lacking a contribution of endothelial cells within the developing anlagen.
Metabolic rewiring and redox alterations in malignant pleural mesothelioma
Authors: Urso Loredana , Cavallari Ilaria , Sharova Evgeniya , Ciccarese Francesco , Pasello Giulia , Ciminale Vincenzo 
Published: December 2019

AbstractMalignant pleural mesothelioma (MPM) is a rare malignancy of mesothelial cells with increasing incidence, and in many cases, dismal prognosis due to its aggressiveness and lack of effective therapies. Environmental and occupational exposure to asbestos is considered the main aetiological factor for MPM. Inhaled asbestos fibres accumulate in the lungs and induce the generation of reactive oxygen species (ROS) due to the presence of iron associated with the fibrous silicates and to the activation of macrophages and inflammation. Chronic inflammation and a ROS-enriched microenvironment can foster the malignant transformation of mesothelial cells. In addition, MPM cells have a highly glycolytic metabolic profile and are positive in18F-FDG PET analysis. Loss-of-function mutations of BRCA-associated protein 1 (BAP1) are a major contributor to the metabolic rewiring of MPM cells. A subset of MPM tumours show loss of the methyladenosine phosphorylase (MTAP) locus, resulting in profound alterations in polyamine metabolism, ATP and methionine salvage pathways, as well as changes in epigenetic control of gene expression. This review provides an overview of the perturbations in metabolism and ROS homoeostasis of MPM cells and the role of these alterations in malignant transformation and tumour progression.
All-trans retinoic acid enhances, and a pan-RAR antagonist counteracts, the stem cell promoting activity of EVI1 in acute myeloid leukemia
Authors: Nguyen Chi Huu , Bauer Katharina , Hackl Hubert , Schlerka Angela , Koller Elisabeth , Hladik Anastasiya , Stoiber Dagmar , Zuber Johannes , Staber Philipp B. , Hoelbl-Kovacic Andrea , Purton Louise E. , Grebien Florian , Wieser Rotraud 
Published: December 2019

AbstractEcotropic virus integration site 1 (EVI1), whose overexpression characterizes a particularly aggressive subtype of acute myeloid leukemia (AML), enhanced anti-leukemic activities of all-trans retinoic acid (atRA) in cell lines and patient samples. However, the drivers of leukemia formation, therapy resistance, and relapse are leukemic stem cells (LSCs), whose properties were hardly reflected in these experimental setups. The present study was designed to address the effects of, and interactions between, EVI1 and retinoids in AML LSCs. We report that Evi1 reduced the maturation of leukemic cells and promoted the abundance, quiescence, and activity of LSCs in an MLL-AF9-driven mouse model of AML. atRA further augmented these effects in an Evi1 dependent manner. EVI1 also strongly enhanced atRA regulated gene transcription in LSC enriched cells. One of their jointly regulated targets, Notch4, was an important mediator of their effects on leukemic stemness. In vitro exposure of leukemic cells to a pan-RAR antagonist caused effects opposite to those of atRA. In vivo antagonist treatment delayed leukemogenesis and reduced LSC abundance, quiescence, and activity in Evi1high AML. Key results were confirmed in human myeloid cell lines retaining some stem cell characteristics as well as in primary human AML samples. In summary, our study is the first to report the importance of EVI1 for key properties of AML LSCs. Furthermore, it shows that atRA enhances, and a pan-RAR antagonist counteracts, the effects of EVI1 on AML stemness, thus raising the possibility of using RAR antagonists in the therapy of EVI1high AML.
Circ_0001955 facilitates hepatocellular carcinoma (HCC) tumorigenesis by sponging miR-516a-5p to release TRAF6 and MAPK11
Authors: Yao Zhicheng , Xu Ruiyun , Yuan Lin , Xu Mingxing , Zhuang Haiyun , Li Yanjie , Zhang Yi , Lin Nan 
Published: December 2019

AbstractCircular RNAs (circRNAs) have been increasingly demonstrated to function as novel promising therapeutic RNA molecules for diverse human diseases, including cancer. Although the important role of circRNAs has been well documented in HCC, the complex mechanisms of circRNAs in HCC need to be elucidated. Here, a novel circRNA circ_0001955 was identified from three GSE datasets (GSE7852, GSE94508, and GSE97322) as a differentially expressed circRNA between HCC and normal samples. We revealed that circ_0001955, TRAF6 and MAPK11 levels were increased, while miR-516a-5p levels were decreased in HCC tumor tissues compared to adjacent normal tissues. Knockdown of circ_0001955 repressed HCC tumor growth in vitro and in vivo, while overexpression of circ_0001955 exhibited the opposite effect. Circ_0001955 was identified as a sponge for miR-145-5p and miR-516a-5p, and TRAF6 and MAPK11 were demonstrated to be two target genes of miR-516a-5p. In conclusion, circ_0001955 facilitated HCC tumorigenesis by sponging miR-516a-5p to release TRAF6 and MAPK11 expression.
A cysteine near the C-terminus of UCH-L1 is dispensable for catalytic activity but is required to promote AKT phosphorylation, eIF4F assembly, and malignant B-cell survival
Authors: Hussain Sajjad , Bedekovics Tibor , Ali Asma , Zaid Omar , May Danielle G. , Roux Kyle J. , Galardy Paul J. 
Published: December 2019

AbstractThe enzyme UCH-L1 is a neuro-endocrine and germinal center B-cell marker that contributes to the development and aggressive behavior of mature B-cell malignancies. While mutations in this enzyme have been associated with Parkinson’s disease, relatively little is known about the molecular features associated with the biochemical activities of UCH-L1. Here we use a survival-based complementation assay and site-directed mutagenesis and identify a novel role for the C-terminus of UCH-L1 in supporting cell survival. The C220 residue is required for UCH-L1 to promote the assembly of mTOR complex 2 and phosphorylation of the pro-survival kinase AKT. While this residue was previously described as a potential farnesylation site, destruction of the putative CAAX motif by adding a C-terminal epitope tag did not interfere with cell survival, indicating an alternate mechanism. We used proximity-based proteomics comparing the proteomes of wild-type and C220S UCH-L1 and identified a selective loss of association with RNA-binding proteins including components of the translation initiation machinery. As a consequence, the C220S mutant did not promote the assembly of the eIF4F complex. These data identify a novel role for the C-terminus of UCH-L1 in supporting pro-survival and metabolic activities in malignant B-cells. This finding may lead to the development of therapeutics with selective activity towards malignancy that potentially avoid neuronal toxicities.
Bioinspired design of flexible armor based on chiton scales
Authors: Connors Matthew , Yang Ting , Hosny Ahmed , Deng Zhifei , Yazdandoost Fatemeh , Massaadi Hajar , Eernisse Douglas , Mirzaeifar Reza , Dean Mason N. , Weaver James C. , Ortiz Christine , Li Ling 
Published: December 2019

AbstractMan-made armors often rely on rigid structures for mechanical protection, which typically results in a trade-off with flexibility and maneuverability. Chitons, a group of marine mollusks, evolved scaled armors that address similar challenges. Many chiton species possess hundreds of small, mineralized scales arrayed on the soft girdle that surrounds their overlapping shell plates. Ensuring both flexibility for locomotion and protection of the underlying soft body, the scaled girdle is an excellent model for multifunctional armor design. Here we conduct a systematic study of the material composition, nanomechanical properties, three-dimensional geometry, and interspecific structural diversity of chiton girdle scales. Moreover, inspired by the tessellated organization of chiton scales, we fabricate a synthetic flexible scaled armor analogue using parametric computational modeling and multi-material 3D printing. This approach allows us to conduct a quantitative evaluation of our chiton-inspired armor to assess its orientation-dependent flexibility and protection capabilities.
New insects feeding on dinosaur feathers in mid-Cretaceous amber
Authors: Gao Taiping , Yin Xiangchu , Shih Chungkun , Rasnitsyn Alexandr P. , Xu Xing , Chen Sha , Wang Chen , Ren Dong 
Published: December 2019

AbstractDue to a lack of Mesozoic fossil records, the origins and early evolution of feather-feeding behaviors by insects are obscure. Here, we report ten nymph specimens of a new lineage of insect, Mesophthirus engeli gen et. sp. nov. within Mesophthiridae fam. nov. from the mid-Cretaceous (ca. 100 Mya) Myanmar (Burmese) amber. This new insect clade shows a series of ectoparasitic morphological characters such as tiny wingless body, head with strong chewing mouthparts, robust and short antennae having long setae, legs with only one single tarsal claw associated with two additional long setae, etc. Most significantly, these insects are preserved with partially damaged dinosaur feathers, the damage of which was probably made by these insects’ integument-feeding behaviors. This finding demonstrates that feather-feeding behaviors of insects originated at least in mid-Cretaceous, accompanying the radiation of feathered dinosaurs including early birds.
Leptin induces TNFα-dependent inflammation in acquired generalized lipodystrophy and combined Crohn’s disease
Authors: Ziegler Jörn F. , Böttcher Chotima , Letizia Marilena , Yerinde Cansu , Wu Hao , Freise Inka , Rodriguez-Sillke Yasmina , Stoyanova Ani K. , Kreis Martin E. , Asbach Patrick , Kunkel Desiree , Priller Josef , Anagnostopoulos Ioannis , Kühl Anja A. , Miehle Konstanze , Stumvoll Michael , Tran Florian , Fredrich Broder , Forster Michael , Franke Andre , Bojarski Christian , Glauben Rainer , Löscher Britt-Sabina , Siegmund Britta , Weidinger Carl 
Published: December 2019

AbstractLeptin has been shown to modulate intestinal inflammation in mice. However, clinical evidence regarding its immune-stimulatory potential in human Crohn’s disease remains sparse. We here describe a patient with the unique combination of acquired generalized lipodystrophy and Crohn’s disease (AGLCD) featuring a lack of adipose tissue, leptin deficiency and intestinal inflammation. Using mass and flow cytometry, immunohistochemistry and functional metabolic analyses, the AGLCD patient was compared to healthy individuals and Crohn’s disease patients regarding immune cell composition, function and metabolism and the effects of recombinant N-methionylleptin (rLeptin) were evaluated. We provide evidence that rLeptin exerts diverse pro-inflammatory effects on immune cell differentiation and function, including the metabolic reprogramming of immune cells and the induction of TNFα, ultimately aggravating Crohn’s disease in the AGLCD patient, which can be reversed by anti-TNFα therapy. Our results indicate that leptin is required for human immune homeostasis and contributes to autoimmunity in a TNFα-dependent manner.
Active generation and magnetic actuation of microrobotic swarms in bio-fluids
Authors: Yu Jiangfan , Jin Dongdong , Chan Kai-Fung , Wang Qianqian , Yuan Ke , Zhang Li 
Published: December 2019

AbstractIn nature, various types of animals will form self-organised large-scale structures. Through designing wireless actuation methods, microrobots can emulate natural swarm behaviours, which have drawn extensive attention due to their great potential in biomedical applications. However, as the prerequisite for their in-vivo applications, whether microrobotic swarms can take effect in bio-fluids with complex components has yet to be fully investigated. In this work, we first categorise magnetic active swarms into three types, and individually investigate the generation and navigation behaviours of two types of the swarms in bio-fluids. The influences of viscosities, ionic strengths and mesh-like structures are studied. A strategy is then proposed to select the optimised swarms in different fluidic environments based on their physical properties, and the results are further validated in various bio-fluids. Moreover, we also realise the swarm generation and navigation in bovine eyeballs, which also validates the proposed prediction in the ex-vivo environment.
Androgen receptor gene expression in primary breast cancer
Authors: Vidula Neelima , Yau Christina , Wolf Denise , Rugo Hope S. 
Published: December 2019

AbstractWe studied androgen receptor (AR) gene expression in primary breast cancer (BC) to determine associations with clinical characteristics and outcomes in the I-SPY 1 study. AR was evaluated in I-SPY 1 (n = 149) using expression microarrays. Associations of AR with clinical and tumor features were determined using the Wilcoxon rank sum test (two-level factors) or the Kruskal–Wallis test (multi-level factors). We identified an optimal AR cut-point to maximize recurrence-free survival (RFS) differences between AR biomarker stratified groups, and assessed the association between the AR stratified groups and RFS using the Cox proportional hazard model. Pearson correlations between AR and selected genes were determined in I-SPY 1, METABRIC (n = 1992), and TCGA (n = 817). AR was lower in triple negative BC vs. hormone receptor positive (HR+)/HER2− and HER2+ disease (p < 0.00001), and lower in basal-like BC (p < 0.00001). AR was higher in grade I/II vs. III tumors (p < 0.00001), in patients >age 50 (p = 0.05), and in node negative disease (p = 0.006). Higher AR was associated with better RFS (p = 0.0007), which remained significant after receptor subtype adjustment (p = 0.01). AR correlated with expression of luminal, HER2, and steroid hormone genes. AR expression was related to clinicopathologic features, intrinsic subtype, and correlated with improved outcome.
FDA oversight of NSIGHT genomic research: the need for an integrated systems approach to regulation
Authors: Milko Laura V. , Chen Flavia , Chan Kee , Brower Amy M. , Agrawal Pankaj B. , Beggs Alan H. , Berg Jonathan S. , Brenner Steven E. , Holm Ingrid A. , Koenig Barbara A. , Parad Richard B. , Powell Cynthia M. , Kingsmore Stephen F. 
Published: December 2019

AbstractThe National Institutes of Health (NIH) funded the Newborn Sequencing In Genomic medicine and public HealTh (NSIGHT) Consortium to investigate the implications, challenges, and opportunities associated with the possible use of genomic sequence information in the newborn period. Following announcement of the NSIGHT awardees in 2013, the Food and Drug Administration (FDA) contacted investigators and requested that pre-submissions to investigational device exemptions (IDE) be submitted for the use of genomic sequencing under Title 21 of the Code of Federal Regulations (21 CFR) part 812. IDE regulation permits clinical investigation of medical devices that have not been approved by the FDA. To our knowledge, this marked the first time the FDA determined that NIH-funded clinical genomic research projects are subject to IDE regulation. Here, we review the history of and rationale behind FDA oversight of clinical research and the NSIGHT Consortium’s experiences in navigating the IDE process. Overall, NSIGHT investigators found that FDA’s application of existing IDE regulations and medical device definitions aligned imprecisely with the aims of publicly funded exploratory clinical research protocols. IDE risk assessments by the FDA were similar to, but distinct from, protocol risk assessments conducted by local Institutional Review Boards (IRBs), and had the potential to reflect novel oversight of emerging genomic technologies. However, the pre-IDE and IDE process delayed the start of NSIGHT research studies by an average of 10 months, and significantly limited the scope of investigation in two of the four NIH approved projects. Based on the experience of the NSIGHT Consortium, we conclude that policies and practices governing the development and use of novel genomic technologies in clinical research urgently need clarification in order to mitigate potentially conflicting or redundant oversight by IRBs, NIH, FDA, and state authorities.