bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagy and Apoptosis in the Midgut Epithelium of Millipedes
Authors: Rost-Roszkowska M.M. , Vilimová J. , Tajovský K. , Chachulska-Żymełka A. , Sosinka A. , Kszuk-Jendrysik M. , Ostróżka A. , Kaszuba F. 
Published: May 2019

AbstractThe process of autophagy has been detected in the midgut epithelium of four millipede species:Julus scandinavius,Polyxenus lagurus,Archispirostreptus gigas, andTelodeinopus aoutii.It has been examined using transmission electron microscopy (TEM), which enabled differentiation of cells in the midgut epithelium, and some histochemical methods (light microscope and fluorescence microscope). While autophagy appeared in the cytoplasm of digestive, secretory, and regenerative cells inJ. scandinaviusandA. gigas, in the two other species,T. aoutiiandP. lagurus, it was only detected in the digestive cells. Both types of macroautophagy, the selective and nonselective processes, are described using TEM. Phagophore formation appeared as the first step of autophagy. After its blind ends fusion, the autophagosomes were formed. The autophagosomes fused with lysosomes and were transformed into autolysosomes. As the final step of autophagy, the residual bodies were detected. Autophagic structures can be removed from the midgut epithelium via, e.g., atypical exocytosis. Additionally, inP. lagurusandJ. scandinavius, it was observed as the neutralization of pathogens such asRickettsia-like microorganisms. Autophagy and apoptosis ca be analyzed using TEM, while specific histochemical methods may confirm it.
Unmet supportive care needs mediate the relationship between functional status and quality of life in patients with amyotrophic lateral sclerosis
Authors: Oh Juyeon , Kim Seung Hyun , Kim Jung A 
Published: May 2019

AbstractObjectiveThe aims of this study were to identify the unmet care needs and to examine the mediating effect of unmet supportive care needs in the relationship between functional status and quality of life (QOL) in Korean patients with amyotrophic lateral sclerosis (ALS).MethodThis was a cross-sectional study conducted among 186 patients with ALS recruited from a tertiary hospital in Seoul, South Korea. ALS patients' functional status, unmet supportive care needs, and QOL were assessed by Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised, the Amyotrophic Lateral Sclerosis Supportive Care Needs Instrument, and the Amyotrophic Lateral Sclerosis Specific Quality of Life – Revised Instrument, respectively. Mediation analysis was tested using Baron and Kenny's regression analysis and a Sobel test.ResultThe mean score for functional status was 33.35 ± 8.89; for unmet supportive care needs it was 2.40 ± 0.66; and for QOL it was 4.95 ± 1.29. Functional status was significantly correlated with unmet care needs and QOL. Unmet care needs satisfaction demonstrated a complete mediating effect on the relationship between functional status and QOL of the patients with ALS (β = –0.53, p < 0.001) and the effect was significant (Sobel test; Z = 5.48, p < 0.001).Significance of resultsAlthough QOL was negatively affected by the functional status in our sample, the relationship was fully mediated via unmet supportive care needs. Because there is no cure for ALS, and the condition is rapidly progressive with a lethal outcome, providing care by meeting patients’ needs is a critical aspect of caring for these patients. Early assessment of supportive care needs, providing services, and referring ALS patients to appropriate resources could enhance their QOL.
Environmental Controls on the Riverine Export of Dissolved Black Carbon
Authors: Jones Matthew W. , de Aragão Luiz E. O. C. , Dittmar Thorsten , de Rezende Carlos E. , Almeida Marcelo G. , Johnson Ben T. , Marques Jomar S. J. , Niggemann Jutta , Rangel Thiago P. , Quine Timothy A. 
Published: May 2019

AbstractEach year, tropical rivers export a dissolved organic carbon (DOC) flux to the global oceans that is equivalent to ~4% of the global land sink for atmospheric CO2. Among the most refractory fractions of terrigenous DOC is dissolved black carbon (DBC), which constitutes ~10% of the total DOC flux and derives from the charcoal and soot (aerosol) produced during biomass burning and fossil fuel combustion. Black carbon (BC) has disproportionate storage potential in oceanic pools and so its export has implications for the fate and residence time of terrigenous organic carbon (OC). In contrast to bulk DOC, there is limited knowledge of the environmental factors that control riverine fluxes of DBC. We thus completed a comprehensive assessment of the factors controlling DBC export in tropical rivers with catchments distributed across environmental gradients of hydrology, topography, climate, and soil properties. Generalized linear models explained 70 and 64% of the observed variance in DOC and DBC concentrations, respectively. DOC and DBC concentrations displayed coupled responses to the dominant factors controlling their riverine export (soil moisture, catchment slope, and catchment stocks of OC or BC, respectively) but varied divergently across gradients of temperature and soil properties. DBC concentrations also varied strongly with aerosol BC deposition rate, indicating further potential for deviation of DBC fluxes from those of DOC due to secondary inputs of DBC from this unmatched source. Overall, this study identifies the specific drivers of BC dynamics in river catchments and fundamentally enhances our understanding of refractory DOC export to the global oceans.
Modeling the Vegetation Dynamics of Northern Shrubs and Mosses in the ORCHIDEE Land Surface Model
Authors: Druel Arsène , Ciais Philippe , Krinner Gerhard , Peylin Philippe 
Published: May 2019

AbstractParameterizations of plant competition processes involving shrubs, mosses, grasses, and trees were introduced with the recently implemented shrubs and mosses plant functional types in the ORCHIDEE dynamic global vegetation model in order to improve the representation of high latitude vegetation dynamics. Competition is based on light capture for growth, net primary productivity, and survival to cold‐induced mortality during winter. Trees are assumed to outcompete shrubs and grasses for light, and shrubs outcompete grasses. Shrubs are modeled to have a higher survival than trees to extremely cold winters because of thermic protection by snow. The fractional coverage of each plant type is based on their respective net primary productivity and winter mortality of trees and shrubs. Gridded simulations were carried out for the historical period and the 21st century following the RCP4.5 and 8.5 scenarios. We evaluate the simulated present‐day vegetation with an observation‐based distribution map and literature data of boreal shrubs. The simulation produces a realistic present‐day boreal vegetation distribution, with shrubs, mosses north of trees and grasses. Nevertheless, the model underestimated local shrub expansion compared to observations from selected sites in the Arctic during the last 30 years suggesting missing processes (nutrients and microscale effects). The RCP4.5 and RCP8.5 projections show a substantial decrease of bare soil, an increase in tree and moss cover and an increase of shrub net primary productivity. Finally, the impact of new vegetation types and associated processes is discussed in the context of climate feedbacks.
Index‐Based Characterization and Quantification of Groundwater Dynamics
Authors: Heudorfer B. , Haaf E. , Stahl K. , Barthel R. 
Published: May 2019

AbstractTime series of groundwater head measurements serve as a primary source of information on groundwater systems. In different groundwater systems, and across several scales, we observe a multitude of patterns in groundwater time series, resulting from complex hydrogeological setups. Unlike in surface hydrology, there is no generalized classification to categorize and quantify the dynamics in groundwater time series. This leads to a lack of tools that could help us disentangle the information contained in groundwater time series in a systematic way. To approach such a classification, we present a principle for organization to qualitatively describe and to quantify groundwater dynamics in a nonredundant and data efficient way. We devise a descriptive typology of groundwater dynamics and assign quantitative measures, mathematically expressing these dynamics. Based on an extensive data set of daily groundwater hydrographs from central Europe, we analyze the relationship between indices and typology based on principal component analysis. The principal component analysis is also used to investigate and discuss redundancy, that is, indices expressing similar information content of hydrographs. Further, the indices' sensitivity to measurement interval and length of the overall observed period is investigated. Finally, a case study demonstrates the potential of the typology and index approach to link groundwater dynamics to the underlying hydrogeological process controls. The tools provided for characterization and quantification of groundwater dynamics should improve future efforts of groundwater classification and prediction in ungauged aquifers and other applications.
Abyssal Transport Variations in the Southwest South Atlantic: First Insights From a Long‐Term Observation Array at 34.5°S
Authors: Valla Daniel , Piola Alberto R. , Meinen Christopher S. , Campos Edmo 
Published: May 2019

AbstractThe zonal structure and time variability of the abyssal flow (below 3,000 dbar) in the South Atlantic western boundary is investigated using a combination of moored observations and simultaneous hydrographic/velocity sections at 34.5°S during 2009–2018. Moored direct velocity measurements near the bottom show strong variability with a peak‐to‐peak range exceeding 80 cm/s and dominant signals at times scales of 1–2 months. Daily time series of the meridional absolute geostrophic volume transport computed from the moorings reveals a highly energetic record with a temporal standard deviation of 8.3 Sv and peak‐to‐peak variations of 49 Sv, suggesting a significant contribution of the abyssal layer flows to the Deep Western Boundary Current time variability. The absolute transport is mostly driven by barotropic changes that are dominated by variations in the bottom pressure ~650 km away from the continental slope.
Validation of Anisotropic Electron Fluid Closure Through In Situ Spacecraft Observations of Magnetic Reconnection
Authors: Wetherton Blake A. , Egedal Jan , Lê Ari , Daughton William 
Published: May 2019

AbstractA valid fluid model for electrons in collisionless space plasmas is desirable for understanding the structure and evolution of magnetic reconnection geometries. Additionally, such a fluid model would be useful for the simulation of systems too large to be tractable in a fully kinetic model. Using Magnetospheric Multiscale spacecraft observations, we provide direct confirmation of the Lê et al., 2009 (https://doi.org/10.1103/PhysRevLett.102.085001) equations of state for the electron pressure tensor during guide field reconnection and demonstrate how the closure can be applied in efficient numerical simulation, yielding new physical insight to the electron heating problem. Furthermore, we use the Lê et al., 2009 equations of state to predict a scaling of electron heating in the exhaust comparable to the available observational data.
Evolution of the Double‐ITCZ Bias Through CESM2 Development
Authors: Woelfle M. D. , Bretherton C. S. , Hannay C. , Neale R. 
Published: May 2019

AbstractThe structure of the east Pacific Intertropical Convergence Zone (ITCZ) as simulated in the Community Earth System Model version 2 (CESM2) is greatly improved as compared to its previous version, CESM version 1. Examination of intermediate model versions created as part of the development process for CESM2 shows the improvement in the ITCZ is well correlated with a reduction in the relative warmth of southeast Pacific sea surface temperatures (SSTs) as compared to the broader tropical mean. Cooling SST in this region enhances the zonal SST and surface pressure gradients and reduces the anomalously southward SST gradient present in boreal spring in early version of CESM2. The improvements in southeast Pacific SST are attributed to increases in low cloud cover and the associated shortwave cloud forcing over the southeast. Sensitivity tests using fixed SST simulations demonstrate the increase in cloud cover between two intermediate model versions, 119 and 125, to be driven by removal of the dependence of autoconversion and accretion rates on cloud water variance as well as the removal of a secondary condensation scheme. Both of these changes reduce drizzle rates in warm clouds increasing cloud lifetime and cloud fraction in the stratocumulus to trade cumulus transition region. The improvements in southeast Pacific shortwave cloud forcing and ITCZ climatology persist through subsequent changes to the cloud microphysics parameterizations. Despite improvements in the east Pacific ITCZ, the global mean ITCZ position and Pacific cold tongue bias strength do not exhibit a systematic improvement across the development simulations.
Patterns of survival in patients with recurrent mantle cell lymphoma in the modern era: progressive shortening in response duration and survival after each relapse
Authors: Kumar Anita , Sha Fushen , Toure Ahmed , Dogan Ahmet , Ni Andy , Batlevi Connie L. , Palomba Maria Lia M. , Portlock Carol , Straus David J. , Noy Ariela , Horwitz Steven M. , Moskowitz Alison , Hamlin Paul , Moskowitz Craig H. , Matasar Matthew J. , Zelenetz Andrew D. , Younes Anas 
Published: May 2019

AbstractAs the survival of patients with mantle cell lymphoma (MCL) continues to improve, patients are increasingly being treated with multiple regimens. However, outcome after each line remains poorly characterized in the modern era. To address this knowledge gap, we retrospectively studied 404 consecutive MCL patients who were managed between 2000 and 2014 at Memorial Sloan Kettering Cancer Center. Histologic diagnosis was centrally confirmed, and patients were followed longitudinally from diagnosis throughout their disease course. Progression-free survival (PFS) and overall survival (OS) were determined by Kaplan–Meier method. The median OS and PFS after first-line treatment were 9.7 and 4.0 years, respectively. After second-line therapy, the median OS and PFS were 41.1 and 14.0 months, third line were 25.2 and 6.5 months, and fourth line were 14.4 and 5.0 months. In patients less than 65 years, stem cell transplant (SCT)-based frontline regimens were associated with improved PFS compared with non-SCT regimens (median PFS: 86.2 versus 40.0 months; P < 0.01), with a trend toward longer OS (median OS: 165.0 versus 120.0 months; P = 0.06). Early treatment failure after first-line regimens was associated with worse OS (5.9 versus 2.5 years; P < 0.01). Our study should facilitate establishing proper endpoints for future clinical trials using novel treatment approaches.
LNK suppresses interferon signaling in melanoma
Authors: Ding Ling-Wen , Sun Qiao-Yang , Edwards Jarem J. , Fernández Lucia Torres , Ran Xue-Bin , Zhou Si-Qin , Scolyer Richard A. , Wilmott James S. , Thompson John F. , Doan Ngan , Said Jonathan W. , Venkatachalam Nachiyappan , Xiao Jin-Fen , Loh Xin-Yi , Pein Maren , Xu Liang , Mullins David W. , Yang Henry , Lin De-Chen , Koeffler H. Phillip 
Published: May 2019

AbstractLNK (SH2B3) is a key negative regulator of JAK-STAT signaling which has been extensively studied in malignant hematopoietic diseases. We found that LNK is significantly elevated in cutaneous melanoma; this elevation is correlated with hyperactive signaling of the RAS-RAF-MEK pathway. Elevated LNK enhances cell growth and survival in adverse conditions. Forced expression of LNK inhibits signaling by interferon-STAT1 and suppresses interferon (IFN) induced cell cycle arrest and cell apoptosis. In contrast, silencing LNK expression by either shRNA or CRISPR-Cas9 potentiates the killing effect of IFN. The IFN-LNK signaling is tightly regulated by a negative feedback mechanism; melanoma cells exposed to IFN upregulate expression of LNK to prevent overactivation of this signaling pathway. Our study reveals an unappreciated function of LNK in melanoma and highlights the critical role of the IFN-STAT1-LNK signaling axis in this potentially devastating disease. LNK may be further explored as a potential therapeutic target for melanoma immunotherapy.
A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis
Authors:   International Multiple Sclerosis Genetics Consortium, Madireddy Lohith , Patsopoulos Nikolaos A. , Cotsapas Chris , Bos Steffan D. , Beecham Ashley , McCauley Jacob , Kim Kicheol , Jia Xiaoming , Santaniello Adam , Caillier Stacy J. , Andlauer Till F. M. , Barcellos Lisa F. , Berge Tone , Bernardinelli Luisa , Martinelli-Boneschi Filippo , Booth David R. , Briggs Farren , Celius Elisabeth G. , Comabella Manuel , Comi Giancarlo , Cree Bruce A. C. , D’Alfonso Sandra , Dedham Katrina , Duquette Pierre , Dardiotis Efthimios , Esposito Federica , Fontaine Bertrand , Gasperi Christiane , Goris An , Dubois Bénédicte , Gourraud Pierre-Antoine , Hadjigeorgiou Georgios , Haines Jonathan , Hawkins Clive , Hemmer Bernhard , Hintzen Rogier , Horakova Dana , Isobe Noriko , Kalra Seema , Kira Jun-ichi , Khalil Michael , Kockum Ingrid , Lill Christina M. , Lincoln Matthew R. , Luessi Felix , Martin Roland , Oturai Annette , Palotie Aarno , Pericak-Vance Margaret A. , Henry Roland , Saarela Janna , Ivinson Adrian , Olsson Tomas , Taylor Bruce V. , Stewart Graeme J. , Harbo Hanne F. , Compston Alastair , Hauser Stephen L. , Hafler David A. , Zipp Frauke , De Jager Philip , Sawcer Stephen , Oksenberg Jorge R. , Baranzini Sergio E. 
Published: May 2019

AbstractGenome-wide association studies (GWAS) have identified more than 50,000 unique associations with common human traits. While this represents a substantial step forward, establishing the biology underlying these associations has proven extremely difficult. Even determining which cell types and which particular gene(s) are relevant continues to be a challenge. Here, we conduct a cell-specific pathway analysis of the latest GWAS in multiple sclerosis (MS), which had analyzed a total of 47,351 cases and 68,284 healthy controls and found more than 200 non-MHC genome-wide associations. Our analysis identifies pan immune cell as well as cell-specific susceptibility genes in T cells, B cells and monocytes. Finally, genotype-level data from 2,370 patients and 412 controls is used to compute intra-individual and cell-specific susceptibility pathways that offer a biological interpretation of the individual genetic risk to MS. This approach could be adopted in any other complex trait for which genome-wide data is available.
Functional cardiac fibroblasts derived from human pluripotent stem cells via second heart field progenitors
Authors: Zhang Jianhua , Tao Ran , Campbell Katherine F. , Carvalho Juliana L. , Ruiz Edward C. , Kim Gina C. , Schmuck Eric G. , Raval Amish N. , da Rocha André Monteiro , Herron Todd J. , Jalife José , Thomson James A. , Kamp Timothy J. 
Published: May 2019

AbstractCardiac fibroblasts (CFs) play critical roles in heart development, homeostasis, and disease. The limited availability of human CFs from native heart impedes investigations of CF biology and their role in disease. Human pluripotent stem cells (hPSCs) provide a highly renewable and genetically defined cell source, but efficient methods to generate CFs from hPSCs have not been described. Here, we show differentiation of hPSCs using sequential modulation of Wnt and FGF signaling to generate second heart field progenitors that efficiently give rise to hPSC-CFs. The hPSC-CFs resemble native heart CFs in cell morphology, proliferation, gene expression, fibroblast marker expression, production of extracellular matrix and myofibroblast transformation induced by TGFβ1 and angiotensin II. Furthermore, hPSC-CFs exhibit a more embryonic phenotype when compared to fetal and adult primary human CFs. Co-culture of hPSC-CFs with hPSC-derived cardiomyocytes distinctly alters the electrophysiological properties of the cardiomyocytes compared to co-culture with dermal fibroblasts. The hPSC-CFs provide a powerful cell source for research, drug discovery, precision medicine, and therapeutic applications in cardiac regeneration.
Krt5+/Krt15+ foregut basal progenitors give rise to cyclooxygenase-2-dependent tumours in response to gastric acid stress
Authors: Moon Hyeongsun , Zhu Jerry , Donahue Leanne R. , Choi Eunju , White Andrew C. 
Published: May 2019

AbstractThe effective prevention of tumor initiation, especially for potentially inoperable tumors, will be beneficial to obtain an overall higher quality of our health and life. Hence, thorough understanding of the pathophysiological mechanisms of early tumor formation arising from identifiable cellular origins is required to develop efficient preventative and early treatment options for each tumor type. Here, using genetically engineered mouse models, we provide preclinical experimental evidence for a long-standing open question regarding the pathophysiological potential of a microenvironmental and physiological stressor in tumor development, gastric acid-mediated regional microscopic injury in foregut squamous epithelia. This study demonstrates the association of gastric acid stress with Cyclooxygenase-2-dependent tumor formation originating from tumor-competent Krt5+/Krt15+ foregut basal progenitor cells. Our findings suggest that clinical management of microenvironmental stressor-mediated microscopic injury may be important in delaying tumor initiation from foregut basal progenitor cells expressing pre-existing tumorigenic mutation(s) and genetic alteration(s).
Time-resolved small-angle neutron scattering as a probe for the dynamics of lipid exchange between human lipoproteins and naturally derived membranes
Authors: Maric Selma , Lind Tania Kjellerup , Raida Manfred Roman , Bengtsson Eva , Fredrikson Gunilla Nordin , Rogers Sarah , Moulin Martine , Haertlein Michael , Forsyth V. Trevor , Wenk Markus R. , Pomorski Thomas Günther , Arnebrant Thomas , Lund Reidar , Cárdenas Marité 
Published: May 2019

AbstractAtherosclerosis is the main killer in the western world. Today’s clinical markers include the total level of cholesterol and high-/low-density lipoproteins, which often fails to accurately predict the disease. The relationship between the lipid exchange capacity and lipoprotein structure should explain the extent by which they release or accept lipid cargo and should relate to the risk for developing atherosclerosis. Here, small-angle neutron scattering and tailored deuteration have been used to follow the molecular lipid exchange between human lipoprotein particles and cellular membrane mimics made of natural, “neutron invisible” phosphatidylcholines. We show that lipid exchange occurs via two different processes that include lipid transfer via collision and upon direct particle tethering to the membrane, and that high-density lipoprotein excels at exchanging the human-like unsaturated phosphatidylcholine. By mapping the specific lipid content and level of glycation/oxidation, the mode of action of specific lipoproteins can now be deciphered. This information can prove important for the development of improved diagnostic tools and in the treatment of atherosclerosis.