bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical Simulations of High‐Frequency Gravity Wave Propagation Through Fine Structures in the Mesosphere
Authors: Mixa Tyler , Fritts David , Lund Thomas , Laughman Brian , Wang Ling , Kantha Lakshmi
Published: August 2019

An anelastic numerical model is used to study the influences of fine structure (FS) in the wind and stability profiles on gravity wave (GW) propagation in the Mesosphere and Lower Thermosphere (MLT). Large amplitude GWs interacting with FS, that is, thin regions of enhanced wind and stability, evolve very differently depending on the precise vorticity source and sink terms for small‐scale motions induced by the FS gradients. The resulting small‐scale dynamics are deterministic, promoting local instabilities, dissipation, and momentum deposition at locations and orientations determined by the initial FS. The resulting momentum depositions yield significant changes to the background wind structure, having scales and amplitudes comparable to the effects of large‐scale features in the ambient atmosphere. The deterministic nature of the large‐scale impacts further suggests that they can be estimated without fully resolving the underlying instability dynamics. Given the significant amplitudes and ubiquitous occurrence of FS throughout the atmosphere, the influences of these important and diverse flow evolutions merit inclusion in broader modeling efforts.
Holocene Formation of Henry Ice Rise, West Antarctica, Inferred From Ice‐Penetrating Radar
Authors: Wearing Martin G. , Kingslake Jonathan
Published: August 2019

Ice rises are regions of grounded ice embedded within floating ice shelves. The deformation of ice past them increases the back stress generated by the ice shelf, slowing the flow of the ice sheet. We present ground‐based ice‐penetrating radar data from Henry Ice Rise in the Ronne Ice Shelf, West Antarctica, that indicates regrounding during the Holocene. Relic crevasses and melt synclines are observed upstream of the present‐day grounding line. We conclude that these features formed during a previous flow configuration, from which the grounding line has since advanced to its current position. In agreement with previous work, our observations can be explained if initial grounding of the ice shelf occurred on a bathymetric high, forming an ice rumple that migrated upstream and temporarily ungrounded over the topographic high. The grounding line then advanced, preserving relic basal crevasses in the newly grounded ice. Using a simple ice‐flow model, we simulate the burial of these crevasses. While accounting for uncertainty in accumulation, firn density, radar‐derived depth, ice‐thickening history, initial crevasse height, and glacial isostatic adjustment, we estimate a burial time of 6 ± 2 kyr before present for the oldest relic crevasses, indicating that the ice rise formed at approximately this time. This potentially increased the buttressing generated by the Ronne Ice Shelf, causing thickening and advance of the ice sheet. By dating the formation and providing details of ice‐rise formation, these new results can provide useful constraints on both large‐scale ice‐sheet models and models of ice‐rumple and ice‐rise formation.
No Proportional Increase of Terrestrial Gross Carbon Sequestration From the Greening Earth
Authors: Zhang Yulong , Song Conghe , Band Lawrence E. , Sun Ge
Published: August 2019

Terrestrial vegetation, as the key component of the biosphere, has a greening trend since the beginning of this century. However, how this substantial greening translated to global gross carbon sequestration or gross primary production (GPP) is not clear. Here we investigated terrestrial GPP dynamics and the respective contributions of climate change and vegetation cover change (VCC) from 2000 to 2015. We adopted a remote sensing based data‐driven model, which was calibrated based on the global eddy flux data set (FLUXNET2015) and Moderate Resolution Imaging Spectroradiometer vegetation index data (Collection 6). A series of simulation experiments were conducted to disaggregate the effects of climate and VCC. We found a much weaker increase in global GPP (0.08%/year; P = 0.07) when compared with the global greening rate (0.23%/year; P < 0.001). The positive effect of VCC on GPP was reduced by 53% due to climate stress. Enhanced global GPP were largely contributed by nonforests, especially croplands. However, tropical forests, once a major driver of the global GPP increase, negatively contributed to global GPP trend due to warming‐induced moisture stress and deforestation. Given the limited potential of cropland carbon storage due to harvest and consumption, the contrasting GPP changes (i.e., cropland GPP increase vs. forest GPP reduction) may have shifted the distribution of the land carbon sink. Our study highlights the potential vulnerability of terrestrial gross carbon sequestration under climate and land use changes and has important implications in the global carbon cycle and climate warming mitigation.
Future Hot and Dry Years Worsen Nile Basin Water Scarcity Despite Projected Precipitation Increases
Authors: Coffel Ethan D. , Keith Bruce , Lesk Corey , Horton Radley M. , Bower Erica , Lee Jonathan , Mankin Justin S.
Published: August 2019

Compound extremes—particularly hot and dry years—can reduce crop yields and result in acute water scarcity. These risks are particularly pronounced in the Upper Nile Basin, a chronically water stressed agricultural region that includes western Ethiopia, South Sudan, and Uganda. While the causes of humanitarian crises in the Nile Basin are complex and involve governance, conflict, and climate, we demonstrate that nearly all recent regional crop failures have occurred amid hot and dry conditions and low runoff supplies. Using an observational ensemble, we find that such hot and dry years have been more frequent in recent decades, driven by increasing regional temperatures. This trend is likely to continue despite climate model projections of increasing regional precipitation. By the late 21st century, the frequency of hot and dry years may rise by a factor of 1.5–3, even if warming is limited to 2 °C. Regional water scarcity will continue to be a chronic issue for the Upper Nile from population growth alone, but runoff deficits during future hot and dry years will amplify this effect, leaving an additional 5–15% of the future population facing water scarcity. Climate change, along with the region's complex water politics, dependence on subsistence agriculture, and history of geopolitical instability, places the region at risk of severe food and water shortages as hot and dry years become more frequent. Adaptation and climate‐resilient water management policies informed by an understanding of compound extremes will be essential to manage these risks.
Changes in the Dust‐Influenced Biological Carbon Pump in the Canary Current System: Implications From a Coastal and an Offshore Sediment Trap Record Off Cape Blanc, Mauritania
Authors: Fischer G. , Romero O. , Toby E. , Iversen M. , Donner B. , Mollenhauer G. , Nowald N. , Ruhland G. , Klann M. , Hamady B. , Wefer G.
Published: August 2019

Long‐term data characterizing the oceans' biological carbon pump are essential for understanding impacts of climate variability on marine ecosystems. The “Bakun upwelling intensification hypothesis” suggests intensified coastal upwelling due to a greater land‐sea temperature gradient influenced by global warming. We present long time series of bathypelagic (approximately 1,200–3,600 m) particle fluxes from a coastal (CBeu: 2003–2016) and an offshore (CBmeso: 1988–2016) sediment trap setting located in the Canary Current upwelling. Organic carbon (Corg) and biogenic opal (BSi, diatoms) fluxes were twofold to threefold higher at the coastal upwelling site compared to the offshore site, respectively, and showed higher seasonality with flux maxima in spring. A relationship between winter and spring BSi fluxes to the North Atlantic Oscillation index was best expressed at the offshore site CBmeso. Lithogenic (dust) fluxes regularly peaked in winter when frequent low‐altitude dust storms and deposition occurred, decreasing offshore by about threefold. We obtained a high temporal match of short‐term peaks of BSi and dust fluxes in winter to spring at the inner site CBeu. We found synchronous flux variations at both sites and an anomalous year 2005, characterized by high BSi and Corg fluxes under a low North Atlantic Oscillation. Corg and BSi fluxes revealed a decreasing trend from 2006 to 2016 at the coastal site CBeu, pointing to coastal upwelling relaxation during the last two decades. The permanent offshore upwelling zone of the deflected Canary Current represented by the flux record of CBmeso showed no signs of increasing upwelling as well which contradicts the Bakun hypothesis.
Emersion of Distal Domains in Advanced Stages of Continental Rifting Explained by Asynchronous Crust and Mantle Necking
Authors: Chenin Pauline , Manatschal Gianreto , Decarlis Alessandro , Schmalholz Stefan M. , Duretz Thibault , Beltrando Marco
Published: August 2019

We propose an explanation to the enigmatic synrift erosional unconformities reported along the distal domain of several magma‐poor rifted margins. Using thermomechanical numerical modeling, we show that transient emersion of (future) distal domains following a phase of subsidence can be explained by asynchronous necking of first the upper mantle and subsequently the crust, without the need of prominent normal faulting caused by strain softening, mantle phase transitions, or magmatic processes. When the upper crust and upper mantle are mechanically decoupled by a weak lower crust and, in the absence of any prominent rheological heterogeneity, upper mantle, necking starts first because of the higher deviatoric stresses associated with its larger effective viscosity. Consequently, the ductile lower crustal material flows toward the necked mantle domain, delaying thinning of the overlying crust. Once the necked lithospheric mantle has locally lost most of its strength, the overdeepened Moho moves upward toward an isostatically compensated depth. This flexural rebound causes uplift and emersion of distal parts of the rift system that are composed of still relatively thick crust and triggers the necking of the overlying crust. Early necking of the upper mantle causes a transient heating event with temperatures up to 750 °C at the base of the crust in the (future) distal domain. The onset of this thermal event slightly predates emersion of the (future) distal domain. These results are consistent with field observations and thermochronological data from the fossil Alpine Tethys margins, as well as with seismic observations from several present‐day rifted margins.
On the Role of Reduced Air Density Along the Lightning Leader Path to Ground in Increasing X‐Ray Production Relative to Normal Atmospheric Conditions
Authors: Tran M. D. , Kereszy I. , Rakov V. A. , Dwyer J. R.
Published: August 2019

Mallick et al. (2012, https://doi.org/10.1029/2012JD017555) discovered that subsequent‐stroke leaders in natural negative lightning could be more prolific producers of hard X‐rays and gamma rays than the first‐stroke leader in the same flash. However, they had no optical records to confirm that their subsequent leaders followed the same path to ground as the first leader, as opposed to forging a new path to ground through cold air. In this paper, we present new observations, including optical data, showing that a second stroke produced more detectable X‐ray pulses than the first stroke, with both strokes following the same channel to ground. Additionally, we present data for the fifth stroke from a different flash, which show the occurrence of X‐ray emission at the onset of the common streamer zone between the hot channels of the downward negative dart‐stepped leader and upward positive connecting leader. However, there were no detectable X‐rays associated with negative leader steps.
The Modulation of Solar Wind Hydrogen Deposition in the Martian Atmosphere by Foreshock Phenomena
Authors: Fowler C. M. , Halekas J. , Schwartz S. , Goodrich K. A. , Gruesbeck J. R. , Benna M.
Published: August 2019

The neutral exosphere of Mars extends far upstream beyond the bow shock, and as a result, solar wind protons can charge exchange with this neutral exosphere to produce energetic neutral atoms. Energetic neutral atoms produced directly upstream of Mars will precipitate into the Martian dayside atmosphere, where some fraction can undergo a charge stripping reaction and can be observed as “penetrating protons.” Clear, quasiperiodic modulations in penetrating proton densities are observed during certain Mars Atmosphere and Volatile EvolutioN (MAVEN) periapsis passes, and we show that these modulations occur during radial interplanetary magnetic field conditions. During such times, the region sunward of Mars is defined by quasi‐parallel shock conditions, generating foreshock structures characterized by enhancements in magnetic field strength, enhancements in proton density, and deceleration and deflection of the solar wind flow. These structures are observed at time cadences equal to the modulation of penetrating proton densities at periapsis. Particle tracing simulations show that the convection of these structures with the solar wind leads to localized enhancements in the rate of charge exchange upstream of the shock, producing the observed temporal variations in penetrating proton densities at periapsis. The observation of modulated penetrating proton densities at periapsis can thus be used to infer the existence of radial interplanetary magnetic field conditions upstream of the bow shock at Mars at times when MAVEN does not sample the upstream solar wind.
Physical Drivers of Phytoplankton Bloom Initiation in the Southern Ocean's Scotia Sea
Authors: Prend Channing J. , Gille Sarah T. , Talley Lynne D. , Mitchell B. Greg , Rosso Isabella , Mazloff Matthew R.
Published: August 2019

The Scotia Sea is the site of one of the largest spring phytoplankton blooms in the Southern Ocean. Past studies suggest that shelf‐iron inputs are responsible for the high productivity in this region, but the physical mechanisms that initiate and sustain the bloom are not well understood. Analysis of profiling float data from 2002 to 2017 shows that the Scotia Sea has an unusually shallow mixed‐layer depth during the transition from winter to spring, allowing the region to support a bloom earlier in the season than elsewhere in the Antarctic Circumpolar Current. We compare these results to the mixed‐layer depth in the 1/6° data‐assimilating Southern Ocean State Estimate and then use the model output to assess the physical balances governing mixed‐layer variability in the region. Results indicate the importance of lateral advection of Weddell Sea surface waters in setting the stratification. A Lagrangian particle release experiment run backward in time suggests that Weddell outflow constitutes 10% of the waters in the upper 200 m of the water column in the bloom region. This dense Weddell water subducts below the surface waters in the Scotia Sea, establishing a sharp subsurface density contrast that cannot be overcome by wintertime convection. Profiling float trajectories are consistent with the formation of Taylor columns over the region's complex bathymetry, which may also contribute to the unique stratification. Furthermore, biogeochemical measurements from 2016 and 2017 bloom events suggest that vertical exchange associated with this Taylor column enhances productivity by delivering nutrients to the euphotic zone.
Phylogenetic, genomic, and biogeographic characterization of a novel and ubiquitous marine invertebrate-associated Rickettsiales parasite, Candidatus Aquarickettsia rohweri, gen. nov., sp. nov
Authors: Klinges J Grace , Rosales Stephanie M , McMinds Ryan , Shaver Elizabeth C , Shantz Andrew A , Peters Esther C , Eitel Michael , Wörheide Gert , Sharp Koty H , Burkepile Deron E , Silliman Brian R , Vega Thurber Rebecca L
Published: August 2019

Bacterial symbionts are integral to the health and homeostasis of invertebrate hosts. Notably, members of the Rickettsiales genus Wolbachia influence several aspects of the fitness and evolution of their terrestrial hosts, but few analogous partnerships have been found in marine systems. We report here the genome, phylogenetics, and biogeography of a ubiquitous and novel Rickettsiales species that primarily associates with marine organisms. We previously showed that this bacterium was found in scleractinian corals, responds to nutrient exposure, and is associated with reduced host growth and increased mortality. This bacterium, like other Rickettsiales, has a reduced genome indicative of a parasitic lifestyle. Phylogenetic analysis places this Rickettsiales within a new genus we define as “Candidatus Aquarickettsia.” Using data from the Earth Microbiome Project and SRA databases, we also demonstrate that members of “Ca. Aquarickettsia” are found globally in dozens of invertebrate lineages. The coral-associated “Candidatus A. rohweri” is the first finished genome in this new clade. “Ca. A. rohweri” lacks genes to synthesize most sugars and amino acids but possesses several genes linked to pathogenicity including Tlc, an antiporter that exchanges host ATP for ADP, and a complete Type IV secretion system. Despite its inability to metabolize nitrogen, “Ca. A. rohweri” possesses the NtrY-NtrX two-component system involved in sensing and responding to extracellular nitrogen. Given these data, along with visualization of the parasite in host tissues, we hypothesize that “Ca. A. rohweri” reduces coral health by consuming host nutrients and energy, thus weakening and eventually killing host cells. Last, we hypothesize that nutrient enrichment, which is increasingly common on coral reefs, encourages unrestricted growth of “Ca. A. rohweri” in its host by providing abundant N-rich metabolites to be scavenged.
Altered orbitofrontal sulcogyral patterns in gambling disorder: a multicenter study
Authors: Li Yansong , Wang Zixiang , Boileau Isabelle , Dreher Jean-Claude , Gelskov Sofie , Genauck Alexander , Joutsa Juho , Kaasinen Valtteri , Perales José C. , Romanczuk-Seiferth Nina , Ruiz de Lara Cristian M. , Siebner Hartwig R. , van Holst Ruth J. , van Timmeren Tim , Sescousse Guillaume
Published: August 2019

Gambling disorder is a serious psychiatric condition characterized by decision-making and reward processing impairments that are associated with dysfunctional brain activity in the orbitofrontal cortex (OFC). However, it remains unclear whether OFC functional abnormalities in gambling disorder are accompanied by structural abnormalities. We addressed this question by examining the organization of sulci and gyri in the OFC. This organization is in place very early and stable across life, such that OFC sulcogyral patterns (classified into Types I, II, and III) can be regarded as potential pre-morbid markers of pathological conditions. We gathered structural brain data from nine existing studies, reaching a total of 165 individuals with gambling disorder and 159 healthy controls. Our results, supported by both frequentist and Bayesian statistics, show that the distribution of OFC sulcogyral patterns is skewed in individuals with gambling disorder, with an increased prevalence of Type II pattern compared with healthy controls. Examination of gambling severity did not reveal any significant relationship between OFC sulcogyral patterns and disease severity. Altogether, our results provide evidence for a skewed distribution of OFC sulcogyral patterns in gambling disorder and suggest that pattern Type II might represent a pre-morbid structural brain marker of the disease. It will be important to investigate more closely the functional implications of these structural abnormalities in future work.
The effects of deep-brain non-stimulation in severe obsessive-compulsive disorder: an individual patient data meta-analysis
Authors: Schruers Koen , Baldi Samantha , van den Heuvel Tijl , Goossens Liesbet , Luyten Laura , Leentjens Albert. F. G. , Ackermans Linda , Temel Yasin , Viechtbauer Wolfgang
Published: August 2019

Non-intervention-related effects have long been recognized in an array of medical interventions, to which surgical procedures like deep-brain stimulation are no exception. While the existence of placebo and micro-lesion effects has been convincingly demonstrated in DBS for major depression and Parkinson’s disease, systematic investigations for obsessive-compulsive disorder (OCD) are currently lacking. We therefore undertook an individual patient data meta-analysis with the aim of quantifying the effect of DBS for severe, treatment-resistant OCD that is not due to the electrical stimulation of brain tissue. The MEDLINE/PubMed database was searched for double-blind, sham-controlled randomized clinical trials published in English between 1998 and 2018. Individual patient data was obtained from the original authors and combined in a meta-analysis. We assessed differences from baseline in obsessive-compulsive symptoms following sham treatment, as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Four studies met the inclusion criteria, randomizing 49 patients to two periods of active or sham stimulation. To preclude confounding by period effects, our estimate was based only on data from those patients who underwent sham stimulation first (n = 24). We found that sham stimulation induced a significant change in the Y-BOCS score (t = −3.15, P < 0.005), lowering it by 4.9 ± 1.6 points [95% CI = (−8.0, –1.8)]. We conclude that non-stimulation-related effects of DBS exist also in OCD. The identification of the factors determining the magnitude and occurrence of these effects will help to design strategies that will ultimately lead to a betterment of future randomized clinical trials.
Association of elevated serumfree light chains with chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis
Authors: Clay-Gilmour Alyssa I. , Rishi Abdul R. , Goldin Lynn R. , Greenberg-Worisek Alexandra J. , Achenbach Sara J. , Rabe Kari G. , Maurer Matthew J. , Kay Neil E. , Shanafelt Tait D. , Call Timothy G. , Brice Weinberg J. , Camp Nicola J. , Cerhan James R. , Leis Jose , Norman Aaron , Murray David L. , Vincent Rajkumar S. , Caporaso Neil E. , Landgren Ola , McMaster Mary L. , Slager Susan L. , Vachon Celine M.
Published: August 2019

Chronic lymphocytic leukemia (CLL) and its precursor, monoclonal B-cell lymphocytosis (MBL), are heritable. Serumfree light-chain (sFLC) measures are a prognostic factor for CLL, but their role in susceptibility to CLL is not clear. We investigated differences between sFLC measurements in pre-treatment serum from five groups to inform the association of sFLC with familial and sporadic CLL: (1) familial CLL (n = 154), (2) sporadic CLL (n = 302), (3) familial MBL (n = 87), (4) unaffected first-degree relatives from CLL/MBL families (n = 263), and (5) reference population (n = 15,396). The percent of individuals having elevated monoclonal and polyclonal sFLCs was compared using age-stratified and age- and sex-adjusted logistic regression models. In age groups >50 years, monoclonal sFLC elevations were increased in sporadic and familial CLL cases compared to the reference population (p’s < 0.05). However, there were no statistically significant differences in sFLC monoclonal or polyclonal elevations between familial and sporadic CLL cases (p’s > 0.05). Unaffected relatives and MBL cases from CLL/MBL families, ages >60 years, showed elevated monoclonal sFLC, compared to the reference population (p’s < 0.05). This is the first study to demonstrate monoclonal sFLC elevations in CLL cases compared to controls. Monoclonal sFLC levels may provide additional risk information in relatives of CLL probands.
Inhibition of ZIP4 reverses epithelial-to-mesenchymal transition and enhances the radiosensitivity in human nasopharyngeal carcinoma cells
Authors: Zeng Qi , Liu Yi-min , Liu Jun , Han Jian , Guo Jian-xin , Lu Shun , Huang Xue-mei , Yi Ping , Lang Jin-yi , Zhang Peng , Wang Chun-ting
Published: August 2019

ZIP4 is a zinc transporter involved in epithelial cell morphology and migration in various cancers. In the epithelial-to-mesenchymal transition (EMT), epithelial cells transition into mesenchymal cells. The EMT plays a crucial role in invasiveness and metastasis during tumorigenesis. The aim of this study was to investigate the role of ZIP4 in the invasiveness and radiosensitivity of human nasopharyngeal carcinoma (NPC). In this study, results from 99 human patients with NPC showed that ZIP4 expression levels significantly correlated with a higher TN (tumor, lymph node) classification, as well as shorter overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). Forced overexpression of ZIP4 promoted the migration and invasion of C666-1 cells through regulation of the EMT process. In contrast, ZIP4 silencing by lentivirus-mediated shRNA inhibited the EMT and metastasis of C666-1 cells in vitro and in vivo. Importantly, protein microarray analyses showed that downregulation of ZIP4 in C666-1 cells resulted in the decreased abundance of phosphoinositide 3-kinase (PI3K) p85 (Tyr607), phosphorylated (p)-Akt (Ser473), phosphorylated (p)-Akt (Thr308), and phosphorylated glycogen synthase kinase 3β (pGSK3β; Ser9). These data suggest that ZIP4 induces the EMT and promotes migration and invasion via the PI3K/Akt signaling pathway in NPC. Moreover, ZIP4 silencing significantly enhanced radiation-induced apoptosis and growth inhibition of human C666-1 cells in vitro and enhanced the antitumor activity of ionizing radiation (IR), leading to tumor growth inhibition in vivo. These results demonstrate that ZIP4 is a novel prognostic factor for malignant NPC progression. More importantly, targeting ZIP4, along with radiotherapy, may be an effective new treatment for NPC.
Inhibition of transmembrane TNF-α shedding by a specific antibody protects against septic shock
Authors: Li Chenxi , Gu Haiyan , Yu Mingxia , Yang Peng , Zhang Meng , Ba Hongping , Yin Yue , Wang Jing , Yin Bingjiao , Zhou Xiaoxi , Li Zhuoya
Published: August 2019

Transmembrane TNF-α (tmTNF-α) and secretory TNF-α (sTNF-α) display opposite effects in septic shock. Reducing tmTNF-α shedding can offset the detrimental effects of sTNF-α and increase the beneficial effect of tmTNF-α. We previously developed a monoclonal antibody that is specific for tmTNF-α and does not cross-react with sTNF-α. In this study, we show that this antibody can specifically suppress tmTNF-α shedding by competing with a TNF-α converting enzyme that cleaves the tmTNF-α ectodomain to release sTNF-α. This tmTNF-α antibody significantly inhibited LPS-induced secretion of interleukin (IL)-1β, IL-6, interferon-β, and nitric oxide by monocytes/macrophages, and protected mice from septic shock induced by lipopolysaccharide (LPS) or cecal ligation and puncture, while reducing the bacterial load. The mechanism associated with the protective effect of this tmTNF-α antibody involved promotion of LPS-induced toll-like receptor 4 (TLR4) internalization and degradation by recruiting Triad3A to TLR4. Moreover, the tmTNF-α antibody inhibited LPS-induced activation of nuclear factor-κB and interferon regulatory factor 3 pathways by upregulating expression of A20 and monocyte chemotactic protein-induced protein 1. Similarly, treatment of macrophages with exogenous tmTNF-α suppressed LPS/TLR4 signaling and release of proinflammatory cytokines, indicating that increased levels of tmTNF-α promoted by the antibody contributed to its inhibitory effect. Thus, use of this tmTNF-α antibody for specific suppression of tmTNF-α shedding may be a promising strategy to treat septic shock.
Long noncoding RNA DANCR regulates proliferation and migration by epigenetically silencing FBP1 in tumorigenesis of cholangiocarcinoma
Authors: Wang Ni , Zhang Chongguo , Wang Wulin , Liu Jie , Yu Yang , Li You , Zhang Mingjiong , Ge Xianxiu , Li Quanpeng , Miao Lin
Published: August 2019

Recently, long noncoding RNAs (lncRNAs) have been shown to play significant regulatory roles in human tumorigenesis. However, the biological function of lncRNAs in cholangiocarcinoma (CCA) remains largely unknown. In this study, DANCR was shown to be significantly upregulated in CCA. DANCR regulated the proliferation and migration of CCA cells in vitro. Moreover, downregulation of DANCR suppressed CCA cells proliferation in vivo. RNA-seq revealed that DANCR knockdown preferentially affected genes linked with cell proliferation and cell differentiation. Furthermore, mechanistic investigation validated that DANCR could bind EZH2 and modulate the histone methylation of promoter of FBP1, thereby regulating CCA cells growth and migration. Taken together, these results demonstrated the significant roles of DANCR in CCA and may provide a theoretical basis for clinical diagnosis and treatment of CCA.
A metasomatized lithospheric mantle control on the metallogenic signature of post-subduction magmatism
Authors: Holwell David A. , Fiorentini Marco , McDonald Iain , Lu Yongjun , Giuliani Andrea , Smith Daniel J. , Keith Manuel , Locmelis Marek
Published: August 2019

Ore deposits are loci on Earth where energy and mass flux are greatly enhanced and focussed, acting as magnifying lenses into metal transport, fractionation and concentration mechanisms through the lithosphere. Here we show that the metallogenic architecture of the lithosphere is illuminated by the geochemical signatures of metasomatised mantle rocks and post-subduction magmatic-hydrothermal mineral systems. Our data reveal that anomalously gold and tellurium rich magmatic sulfides in mantle-derived magmas emplaced in the lower crust share a common metallogenic signature with upper crustal porphyry-epithermal ore systems. We propose that a trans-lithospheric continuum exists whereby post-subduction magmas transporting metal-rich sulfide cargoes play a fundamental role in fluxing metals into the crust from metasomatised lithospheric mantle. Therefore, ore deposits are not merely associated with isolated zones where serendipitous happenstance has produced mineralisation. Rather, they are depositional points along the mantle-to-upper crust pathway of magmas and hydrothermal fluids, synthesising the concentrated metallogenic budget available.
Quantifying the impact of public omics data
Authors: Perez-Riverol Yasset , Zorin Andrey , Dass Gaurhari , Vu Manh-Tu , Xu Pan , Glont Mihai , Vizcaíno Juan Antonio , Jarnuczak Andrew F. , Petryszak Robert , Ping Peipei , Hermjakob Henning
Published: August 2019

The amount of omics data in the public domain is increasing every year. Modern science has become a data-intensive discipline. Innovative solutions for data management, data sharing, and for discovering novel datasets are therefore increasingly required. In 2016, we released the first version of the Omics Discovery Index (OmicsDI) as a light-weight system to aggregate datasets across multiple public omics data resources. OmicsDI aggregates genomics, transcriptomics, proteomics, metabolomics and multiomics datasets, as well as computational models of biological processes. Here, we propose a set of novel metrics to quantify the attention and impact of biomedical datasets. A complete framework (now integrated into OmicsDI) has been implemented in order to provide and evaluate those metrics. Finally, we propose a set of recommendations for authors, journals and data resources to promote an optimal quantification of the impact of datasets.
Evaporation-induced sintering of liquid metal droplets with biological nanofibrils for flexible conductivity and responsive actuation
Authors: Li Xiankai , Li Mingjie , Xu Jie , You Jun , Yang Zhiqin , Li Chaoxu
Published: August 2019

Liquid metal (LM) droplets show the superiority in coalescing into integral liquid conductors applicable in flexible and deformable electronics. However, the large surface tension, oxide shells and poor compatibility with most other materials may prevent spontaneous coalescence of LM droplets and/or hybridisation into composites, unless external interventions (e.g., shear and laser) are applied. Here, we show that biological nanofibrils (NFs; including cellulose, silk fibroin and amyloid) enable evaporation-induced sintering of LM droplets under ambient conditions into conductive coating on diverse substrates and free-standing films. The resultants possess an insulating NFs-rich layer and a conductive LM-rich layer, offering flexibility, high reflectivity, stretchable conductivity, electromagnetic shielding, degradability and rapid actuating behaviours. Thus this sintering approach not only extends fundamental knowledge about sintering LM droplets, but also starts a new scenario of producing flexible coating and free-standing composites with flexibility, conductivity, sustainability and degradability, and applicable in microcircuits, wearable electronics and soft robotics.
Evidence of ubiquitous Alfvén pulses transporting energy from the photosphere to the upper chromosphere
Authors: Liu Jiajia , Nelson Chris J. , Snow Ben , Wang Yuming , Erdélyi Robert
Published: August 2019

The multi-million degree temperature increase from the middle to the upper solar atmosphere is one of the most fascinating puzzles in plasma-astrophysics. Although magnetic waves might transport enough energy from the photosphere to heat up the local chromosphere and corona, observationally validating their ubiquity has proved challenging. Here, we show observational evidence that ubiquitous Alfvén pulses are excited by prevalent intensity swirls in the solar photosphere. Correlation analysis between swirls detected at different heights in the solar atmosphere, together with realistic numerical simulations, show that these Alfvén pulses propagate upwards and reach chromospheric layers. We found that Alfvén pulses carry sufficient energy flux (1.9 to 7.7 kW m−2) to balance the local upper chromospheric energy losses (~0.1 kW m−2) in quiet regions. Whether this wave energy flux is actually dissipated in the chromosphere and can lead to heating that balances the losses is still an open question.
Morphing of liquid crystal surfaces by emergent collectivity
Authors: van der Kooij Hanne M. , Semerdzhiev Slav A. , Buijs Jesse , Broer Dirk J. , Liu Danqing , Sprakel Joris
Published: August 2019

Liquid crystal surfaces can undergo topographical morphing in response to external cues. These shape-shifting coatings promise a revolution in various applications, from haptic feedback in soft robotics or displays to self-cleaning solar panels. The changes in surface topography can be controlled by tailoring the molecular architecture and mechanics of the liquid crystal network. However, the nanoscopic mechanisms that drive morphological transitions remain unclear. Here, we introduce a frequency-resolved nanostrain imaging method to elucidate the emergent dynamics underlying field-induced shape-shifting. We show how surface morphing occurs in three distinct stages: (i) the molecular dipoles oscillate with the alternating field (10–100 ms), (ii) this leads to collective plasticization of the glassy network (~1 s), (iii) culminating in actuation of the topography (10–100 s). The first stage appears universal and governed by dielectric coupling. By contrast, yielding and deformation rely on a delicate balance between liquid crystal order, field properties and network viscoelasticity.
Author Correction: Hypervirulent Listeria monocytogenes clones’ adaptation to mammalian gut accounts for their association with dairy products
Authors: Maury Mylène M. , Bracq-Dieye Hélène , Huang Lei , Vales Guillaume , Lavina Morgane , Thouvenot Pierre , Disson Olivier , Leclercq Alexandre , Brisse Sylvain , Lecuit Marc
Published: August 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Primary coenzyme Q10 deficiency-7: expanded phenotypic spectrum and a founder mutation in southern Chinese
Authors: Yu Mullin Ho-Chung , Tsang Mandy Ho-Yin , Lai Sophie , Ho Matthew Sai-Pong , Tse Donald M. L. , Willis Brooke , Kwong Anna Ka-Yee , Chou Yen-Yin , Lin Shuan-Pei , Quinzii Catarina M , Hwu Wuh-Liang , Chien Yin-Hsiu , Kuo Pao-Lin , Chan Victor Chi-Man , Tsoi Cheung , Chong Shuk-Ching , Rodenburg Richard J. T. , Smeitink Jan , Mak Christopher Chun-Yu , Yeung Kit-San , Fung Jasmine Lee-Fong , Lam Wendy , Hui Joannie , Lee Ni-Chung , Fung Cheuk‐Wing , Chung Brian Hon-Yin
Published: August 2019

Primary coenzyme Q10 deficiency-7 (COQ10D7) is a rare mitochondrial disease caused by biallelic mutations in COQ4. Here we report the largest cohort of COQ10D7 to date, with 11 southern Chinese patients confirmed with biallelic COQ4 mutations. Five of them have the classical neonatal-onset encephalo-cardiomyopathy, while the others have infantile onset with more heterogeneous clinical presentations. We also identify a founder mutation COQ4 (NM_016035.5): c.370G>A, p.(Gly124Ser) for COQ10D7, suggesting a higher chance of occurrence in the southern Chinese. This study helps improve understanding of the clinical spectrum of this disorder.
Dopamine affects short-term memory corruption over time in Parkinson’s disease
Authors: Fallon Sean James , Gowell Matthew , Maio Maria Raquel , Husain Masud
Published: August 2019

Cognitive deficits are a recognised component of Parkinson’s disease (PD). However, particularly within the domain of short-term memory, it is unclear whether these impairments are masked, or caused, by patients’ dopaminergic medication. The effect of medication on pure maintenance in PD patients has rarely been explored, with most assessments examining maintenance intercalated between other executive tasks. Moreover, few studies have utilised methods that can measure the quality of mental representations, which can enable the decomposition of recall errors into their underlying neurocognitive components. Here, we fill this gap by examining pure maintenance in PD patients in high and low dopaminergic states. Participants had to encode the orientation of two stimuli and reproduce these orientations after a short (2 s) or long (8 s) delay. In addition, we also examined the performance of healthy, age-matched older adults to contextualise these effects and determine whether PD represents an exacerbation of the normal ageing process. Patients showed improved recall OFF compared to ON their dopaminergic medication, but only for long-duration trials. Moreover, PD patients OFF their medication actually performed at a level superior to age-matched controls, indicative of a paradoxical enhancement of memory in the low dopaminergic state. The application of a probabilistic model of response selection suggested that PD patients made fewer misbinding errors in the low, compared with high, dopaminergic state for longer-delay trials. Thus, unexpectedly, the mechanisms that prevent memoranda from being corrupted by misbinding over time appear to be enhanced in PD patients OFF dopaminergic medication. Possible explanations for this paradoxical effect are discussed.
Enhanced decision-making through multimodal training
Authors: Zwilling Christopher E. , Daugherty Ana M. , Hillman Charles H. , Kramer Arthur F. , Cohen Neal J. , Barbey Aron K.
Published: August 2019

A central aim of research in the psychological and decision sciences is to establish interventions that enhance performance, investigating the efficacy of modern approaches to improve human inference and decision-making. Whereas the decision sciences have established interventions to reduce decision biases by promoting strategies for critical thought and reasoning, methods from psychology have instead focused on enhancing cognition through skill-based training of executive functions. Contemporary research in psychology has engaged these operations through multi-modal interventions designed to enhance cognition and physical health through training of executive functions, mindfulness meditation, and physical fitness. Despite the comparable aims of research in the psychological and decision sciences, the efficacy of multi-modal interventions to enhance decision-making remain to be established. We therefore conducted a comprehensive, 16-week, randomized controlled trial (RCT) to investigate this issue, enrolling 160 healthy adults in one of four interventions: (1) high-intensity cardioresistance fitness training (HICRT); (2) HICRT and cognitive training of core executive functions; (3) HICRT and cognitive training, along with mindfulness meditation training; or (4) active control training. The results of our RCT demonstrate that HICRT training and multi-modal interventions that also incorporate cognitive training and mindfulness meditation have beneficial effects on decision-making competence. The observed pattern of findings motivate the application of modern interventions from psychology and cognitive neuroscience to enhance human judgment and decision-making in complex, real-world environments.
Constraints to counting bioluminescence producing cells by a commonly used transgene promoter and its implications for experimental design
Authors: Mosaad E. O. , Futrega K. , Seim I. , Gloss B. , Chambers K. F. , Clements J. A. , Doran M. R.
Published: August 2019

It is routine to genetically modify cells to express fluorescent or bioluminescent reporter proteins to enable tracking or quantification of cells in vitro and in vivo. Herein, we characterized the stability of luciferase reporter systems in C4-2B prostate cancer cells in mono-culture and in co-culture with bone marrow-derived mesenchymal stem/stromal cells (BMSC). An assumption made when employing the luciferase reporter is that the luciferase expressing cell number and bioluminescence signal are linearly proportional. We observed instances where luciferase expression was significantly upregulated in C4-2B cell populations when co-cultured with BMSC, resulting in a significant disconnect between bioluminescence signal and cell number. We subsequently characterized luciferase reporter stability in a second C4-2B reporter cell line, and six other cancer cell lines. All but the single C4-2B reporter cell population had stable luciferase reporter expression in mono-culture and BMSC co-culture. Whole-genome sequencing revealed that relative number of luciferase gene insertions per genome in the unstable C4-2B reporter cell population was lesser than stable C4-2B, PC3 and MD-MBA-231 luciferase reporter cell lines. We reasoned that the low luciferase gene copy number and genome insertion locations likely contributed to the reporter gene expression being exquisitely sensitive BMSC paracrine signals. In this study, we show that it is possible to generate a range of stable and reliable luciferase reporter prostate- and breast- cancer cell populations but advise not to assume stability across different culture conditions. Reporter stability should be validated, on a case-by-case basis, for each cell line and culture condition.
Whole transcriptome analysis reveals correlation of long noncoding RNA ZEB1-AS1 with invasive profile in melanoma
Authors: Siena Ádamo Davi Diógenes , Plaça Jéssica Rodrigues , Araújo Luiza Ferreira , de Barros Isabela Ichihara , Peronni Kamila , Molfetta Greice , de Biagi Carlos Alberto Oliveira , Espreafico Enilza Maria , Sousa Josane Freitas , Silva Wilson Araújo
Published: August 2019

Melanoma is the deadliest form of skin cancer, and little is known about the impact of deregulated expression of long noncoding RNAs (lncRNAs) in the progression of this cancer. In this study, we explored RNA-Seq data to search for lncRNAs associated with melanoma progression. We found distinct lncRNA gene expression patterns across melanocytes, primary and metastatic melanoma cells. Also, we observed upregulation of the lncRNA ZEB1-AS1 (ZEB1 antisense RNA 1) in melanoma cell lines. Data analysis from The Cancer Genome Atlas (TCGA) confirmed higher ZEB1-AS1 expression in metastatic melanoma and its association with hotspot mutations in BRAF (B-Raf proto-oncogene, serine/threonine kinase) gene and RAS family genes. In addition, a positive correlation between ZEB1-AS1 and ZEB1 (zinc finger E-box binding homeobox 1) gene expression was verified in primary and metastatic melanomas. Using gene expression signatures indicative of invasive or proliferative phenotypes, we found an association between ZEB1-AS1 upregulation and a transcriptional profile for invasiveness. Enrichment analysis of correlated genes demonstrated cancer genes and pathways associated with ZEB1-AS1. We suggest that the lncRNA ZEB1-AS1 could function by activating ZEB1 gene expression, thereby influencing invasiveness and phenotype switching in melanoma, an epithelial-to-mesenchymal transition (EMT)-like process, which the ZEB1 gene has an essential role.
Modular microfluidic systems cast from 3D-printed molds for imaging leukocyte adherence to differentially treated endothelial cultures
Authors: Hernández Vera Rodrigo , O’Callaghan Paul , Fatsis-Kavalopoulos Nikos , Kreuger Johan
Published: August 2019

Microfluidic systems are very useful for in vitro studies of interactions between blood cells and vascular endothelial cells under flow, and several commercial solutions exist. However, the availability of customizable, user-designed devices is largely restricted to researchers with expertise in photolithography and access to clean room facilities. Here we describe a strategy for producing tailor-made modular microfluidic systems, cast in PDMS from 3D-printed molds, to facilitate studies of leukocyte adherence to endothelial cells. A dual-chamber barrier module was optimized for culturing two endothelial cell populations, separated by a 250 μm wide dividing wall, on a glass slide. In proof-of-principle experiments one endothelial population was activated by TNFα, while the other served as an internal control. The barrier module was thereafter replaced with a microfluidic flow module, enclosing both endothelial populations in a common channel. A suspension of fluorescently-labeled leukocytes was then perfused through the flow module and leukocyte interactions with control and TNFα-treated endothelial populations were monitored in the same field of view. Time-lapse microscopy analysis confirmed the preferential attachment of leukocytes to the TNFα-activated endothelial cells. We conclude that the functionality of these modular microfluidic systems makes it possible to seed and differentially activate adherent cell types, and conduct controlled side-by-side analysis of their capacity to interact with cells in suspension under flow. Furthermore, we outline a number of practical considerations and solutions associated with connecting and switching between the microfluidic modules, and the advantages of simultaneously and symmetrically analyzing control and experimental conditions in such a microfluidic system.
Synaptotagmin-1 enables frequency coding by suppressing asynchronous release in a temperature dependent manner
Authors: Huson Vincent , van Boven Maaike A. , Stuefer Alexia , Verhage Matthijs , Cornelisse L. Niels
Published: August 2019

To support frequency-coded information transfer, mammalian synapses tightly synchronize neurotransmitter release to action potentials (APs). However, release desynchronizes during AP trains, especially at room temperature. Here we show that suppression of asynchronous release by Synaptotagmin-1 (Syt1), but not release triggering, is highly temperature sensitive, and enhances synchronous release during high-frequency stimulation. In Syt1-deficient synapses, asynchronous release increased with temperature, opposite to wildtype synapses. Mutations in Syt1 C2B-domain polybasic stretch (Syt1 K326Q,K327Q,K331Q) did not affect synchronization during sustained activity, while the previously observed reduced synchronous response to a single AP was confirmed. However, an inflexible linker between the C2-domains (Syt1 9Pro) reduced suppression, without affecting synchronous release upon a single AP. Syt1 9Pro expressing synapses showed impaired synchronization during AP trains, which was rescued by buffering global Ca2+ to prevent asynchronous release. Hence, frequency coding relies on Syt1’s temperature sensitive suppression of asynchronous release, an aspect distinct from its known vesicle recruitment and triggering functions.