bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diurnal Cycle of Precipitation and Cloud Clusters in the MJO and ITCZ Over the Indian Ocean
Authors: Kerns Brandon W. , Chen Shuyi S. 
Published: August 2018

AbstractSatellite observations of the diurnal cycle of precipitation and cloud clusters show a dominant nighttime maximum over the tropical Indian Ocean, similar to other basins. The nighttime maximum is associated with the relatively long lifetime of large convective systems that initiated during the afternoon when the sea surface temperature (SST) reached its diurnal maximum as first showed in Chen and Houze (1997, https://doi.org/10.1002/qj.49712353806). Shipborne and island‐based radar data from Dynamics of the Madden‐Julian Oscillation show distinct characteristics of the diurnal cycle in the equatorial region and Intertropical Convergence Zone (ITCZ). A secondary afternoon precipitation maximum occurs under light surface winds (<5 m/s) when the diurnal cycle of SST is large (0.5–1.7 °C) in the equatorial region during the suppressed phase of the Madden‐Julian Oscillation (MJO). The afternoon maximum was from short‐lived convective systems with rain rates >10 mm/hr. In contrast, during the active MJO and in the ITCZ, the secondary afternoon maximum is mostly absent as the surface winds were generally >5 m/s and reduced afternoon SST warming to less than 0.5 °C. The Tropical Rainfall Measurement Mission Multiplatform Precipitation Analysis does not resolve the secondary afternoon maximum in heavier rain rates from short‐lived small systems, but it suggests a more pronounced night‐morning maximum in the ITCZ than in the MJO. Infrared 208‐K cloud cluster analysis show that this difference in the morning maximum was due to the greater number of long‐lasting, large convective systems (>~200 km in diameter) persisting into the morning in the ITCZ.
Lenalidomide and dexamethasone in patients with relapsed multiple myeloma and impaired renal function: PrE1003, a PrECOG study
Authors: Mikhael Joseph , Manola Judith , Dueck Amylou C. , Hayman Suzanne , Oettel Kurt , Kanate Abraham S. , Lonial Sagar , Rajkumar S. Vincent 
Published: August 2018

AbstractRenal insufficiency is common in patients with relapsed multiple myeloma and can often limit choice of therapy. Lenalidomide, a critical agent in the treatment of relapsed multiple myeloma, is renally cleared., This phase I/II trial evaluated the efficacy and safety of lenalidomide with dexamethasone in patients with relapsed multiple myeloma and renal insufficiency. Three groups were treated, with creatinine clearance 30–60 cc/hr (group A), CrCl < 30 not on dialysis (group B), and patients on dialysis (group C) at escalating doses of lenalidomide. A total of 63 patients were treated and no DLTs were observed in phase I. All three groups were able to escalate to full dose lenalidomide 25 mg daily 21/28 days, although due to reduced accrual the phase II component was not entirely completed for groups B and C. Adverse events were as expected, including anemia, diarrhea and fatigue. Ten patients experienced grade 3–4 pneumonia. Overall response rate was 54% across all groups. PFS was 7.5 months and OS was 19.7 months. Lenalidomide can be given at full dose 25 mg daily 21/28 in patients with a CrCl > 30, and can be given daily to those with CrCl < 30, even when on dialysis, at doses of at least 15 mg daily.
Biomimetic delivery of signals for bone tissue engineering
Authors: Dang Ming , Saunders Laura , Niu Xufeng , Fan Yubo , Ma Peter X. 
Published: August 2018

AbstractBone tissue engineering is an exciting approach to directly repair bone defects or engineer bone tissue for transplantation. Biomaterials play a pivotal role in providing a template and extracellular environment to support regenerative cells and promote tissue regeneration. A variety of signaling cues have been identified to regulate cellular activity, tissue development, and the healing process. Numerous studies and trials have shown the promise of tissue engineering, but successful translations of bone tissue engineering research into clinical applications have been limited, due in part to a lack of optimal delivery systems for these signals. Biomedical engineers are therefore highly motivated to develop biomimetic drug delivery systems, which benefit from mimicking signaling molecule release or presentation by the native extracellular matrix during development or the natural healing process. Engineered biomimetic drug delivery systems aim to provide control over the location, timing, and release kinetics of the signal molecules according to the drug’s physiochemical properties and specific biological mechanisms. This article reviews biomimetic strategies in signaling delivery for bone tissue engineering, with a focus on delivery systems rather than specific molecules. Both fundamental considerations and specific design strategies are discussed with examples of recent research progress, demonstrating the significance and potential of biomimetic delivery systems for bone tissue engineering.
Prolyl isomerase Pin1: a promoter of cancer and a target for therapy
Authors: Chen Yang , Wu Ya-ran , Yang Hong-ying , Li Xin-zhe , Jie Meng-meng , Hu Chang-jiang , Wu Yu-yun , Yang Shi-ming , Yang Ying-bin 
Published: August 2018

AbstractPin1 is the only known peptidyl-prolyl cis–trans isomerase (PPIase) that specifically recognizes and isomerizes the phosphorylated Serine/Threonine-Proline (pSer/Thr-Pro) motif. The Pin1-mediated structural transformation posttranslationally regulates the biofunctions of multiple proteins. Pin1 is involved in many cellular processes, the aberrance of which lead to both degenerative and neoplastic diseases. Pin1 is highly expressed in the majority of cancers and its deficiency significantly suppresses cancer progression. According to the ground-breaking summaries by Hanahan D and Weinberg RA, the hallmarks of cancer comprise ten biological capabilities. Multiple researches illuminated that Pin1 contributes to these aberrant behaviors of cancer via promoting various cancer-driving pathways. This review summarized the detailed mechanisms of Pin1 in different cancer capabilities and certain Pin1-targeted small-molecule compounds that exhibit anticancer activities, expecting to facilitate anticancer therapies by targeting Pin1.
Alpha-6 integrin promotes radioresistance of glioblastoma by modulating DNA damage response and the transcription factor Zeb1
Authors: Kowalski-Chauvel Aline , Modesto Anouchka , Gouaze-andersson Valerie , Baricault Laurent , Gilhodes Julia , Delmas Caroline , Lemarie Anthony , Toulas Christine , Cohen-Jonathan-Moyal Elizabeth , Seva Catherine 
Published: August 2018

AbstractRadiotherapy is the cornerstone of glioblastoma (GBM) standard treatment. However, radioresistance of cancer cells leads to an inevitable recurrence. In the present study, we showed that blocking α6-integrin in cells derived from GBM biopsy specimens cultured as neurospheres, sensitized cells to radiation. In cells downregulated for α6-integrin expression, we observed a decrease in cell survival after irradiation and an increase in radio-induced cell death. We also demonstrated that inhibition of α6-integrin expression affects DNA damage checkpoint and repair. Indeed, we observed a persistence of γ-H2AX staining after IR and the abrogation of the DNA damage-induced G2/M checkpoint, likely through the downregulation of the checkpoint kinase CHK1 and its downstream target Cdc25c. We also showed that α6-integrin contributes to GBM radioresistance by controlling the expression of the transcriptional network ZEB1/OLIG2/SOX2. Finally, the clinical data from TCGA and Rembrandt databases demonstrate that GBM patients with high levels of the five genes signature, including α6-integrin and its targets, CHK1, ZEB1, OLIG2 and SOX2, have a significantly shorter overall survival. Our study suggest that α6-integrin is an attractive therapeutic target to overcome radioresistance of GBM cancer cells.
Enhanced articular cartilage regeneration with SIRT1-activated MSCs using gelatin-based hydrogel
Authors: Choi Seong Mi , Lee Kyoung-Mi , Ryu Seung Bae , Park Yoo Jung , Hwang Yeok Gu , Baek Dawoon , Choi Yoorim , Park Kwang Hwan , Park Ki Dong , Lee Jin Woo 
Published: August 2018

AbstractTo investigate the functional effects of resveratrol (RSV) on mesenchymal stem cells (MSCs), we treated MSCs with RSV continuously during ex vivo expansion. MSCs were continuously treated with RSV from passage (P) 0 to P5. A proliferative capacity of RSV-treated MSCs was higher than that of non-treated MSCs and similar with P1-MSCs. Continuous treatment of RSV on MSCs increased the stemness and inhibited the senescence. During chondrogenic differentiation in vitro, RSV-treated MSCs had higher differentiation potential and reduced hypertrophic maturation, which are limitations for hyaline cartilage formation. The histological analysis of micromass demonstrated increased chondrogenic differentiation potential. We further explored the therapeutic effectiveness of this method in a rabbit osteochondral defect model. A rabbit osteochondral defect model was established to investigate the hyaline cartilage regeneration potential of RSV-treated MSCs. Moreover, the cartilage regeneration potential of RSV-treated MSCs was greater than that of untreated MSCs. The expression levels of chondrogenic markers increased and those of hypertrophic markers decreased in RSV-treated MSCs compared with untreated MSCs. Sustained treatment of RSV on MSCs during ex vivo expansion resulted in the maintenance of stemness and enhanced chondrogenic differentiation potential. Consequentially, highly efficient MSCs promoted superior hyaline cartilage regeneration in vivo. This novel treatment method provides a basis for cell-based tissue engineering.
The bHLH transcription factor DEC1 promotes thyroid cancer aggressiveness by the interplay with NOTCH1
Authors: Gallo Cristina , Fragliasso Valentina , Donati Benedetta , Torricelli Federica , Tameni Annalisa , Piana Simonetta , Ciarrocchi Alessia 
Published: August 2018

AbstractAberrant re-activation of transcription factors occurs frequently in cancer. Recently, we found the basic helix-loop-helix transcription factors DEC1 and DEC2 significantly up-regulated in a model of highly aggressive thyroid cancer, raising the hypothesis that these factors might be part of the program driving progression of these tumors. Here, we investigated for the first time the function of DEC1 and DEC2 in thyroid cancer. Using both gain- and loss-of-function approaches, we showed that DEC1 more than DEC2 sustains progression of thyroid cancer by promoting cell growth and invasiveness. We demonstrated that DEC1 controls NOTCH1 expression and that the interplay with the NOTCH pathway is relevant for DEC1 function in thyroid cancer. We confirmed this observation in vivo showing that DEC1 expression is a specific feature of tumor cells, that this transcription factor is significantly over-expressed in all major thyroid cancer histotypes and that its expression correlated with NOTCH1 in these tumors. Finally, we performed RNA-sequencing to define the DEC1-associated gene expression profile in thyroid cancer cells and we discovered that DEC1 drives the expression of many cell cycle-related genes, uncovering a potential new function for this transcription factor in cancer.
RIPK3-MLKL-mediated necroinflammation contributes to AKI progression to CKD
Authors: Chen Hui , Fang Yulu , Wu Jianfeng , Chen Hong , Zou Zhenhuan , Zhang Xiaohong , Shao Jing , Xu Yanfang 
Published: August 2018

AbstractNecroptosis predominates functionally over apoptosis in the pathophysiology of renal ischemia-reperfusion injury (IRI). Inhibition of the core components of the necroptotic pathway—receptor-interacting protein kinase 1 (RIPK1), RIPK3 or mixed lineage kinase domain-like protein (MLKL) reduced renal injury after ischemia/reperfusion (IR). Necrosis can initiate inflammation, which enhances necrosis in a positive feedback loop, subsequently leading to triggering more inflammation, termed as necroinflammation. However, the mechanisms underlying necroinflammation driven by renal tubular cell necroptosis in progression of AKI to CKD are still largely unknown. Here we showed that the upregulated expression and interactions between RIPK3 and MLKL induced necroptosis of renal proximal tubular cells and contributed to NLRP3 inflammasome activation under the conditions of IRI. Gene deletion of Ripk3 or Mlkl ameliorated renal tubular cell necroptosis, macrophage infiltration and NLRP3 inflammasome activation with a reduction in caspase-1 activation and maturation of IL-1β, and then finally reduced interstitial fibrogenesis in the long term after IRI. Bone marrow chimeras confirmed that RIPK3-MLKL-dependent necroptosis is responsible for the initiation of the early renal injury after IRI, and then necroptosis triggered NLRP3 inflammasome activation, which subsequently accelerates necroptosis and triggers more inflammation in an auto-amplification loop. These data indicate that necroinflammation driven by RIPK3-MLKL-dependent necroptosis plays a crucial role in the progression of IRI to CKD.
Foot-and-mouth disease virus induces lysosomal degradation of NME1 to impair p53-regulated interferon-inducible antiviral genes expression
Authors: Feng Huan-Huan , Zhu Zi-Xiang , Cao Wei-Jun , Yang Fan , Zhang Xiang-Le , Du Xiao-Li , Zhang Ke-Shan , Liu Xiang-Tao , Zheng Hai-Xue 
Published: August 2018

AbstractNucleoside diphosphate kinase 1 (NME1) is well-known as a tumor suppressor that regulates p53 function to prevent cancer metastasis and progression. However, the role of NME1 in virus-infected cells remains unknown. Here, we showed that NME1 suppresses viral replication in foot-and-mouth disease virus (FMDV)-infected cells. NME1-enhanced p53-mediated transcriptional activity and induction of interferon-inducible antiviral genes expression. FMDV infection decreased NME1 protein expression. The 2B and VP4 proteins were identified as the viral factors that induced reduction of NME1. FMDV 2B protein has a suppressive effect on host protein expression. We measured, for the first time, VP4-induced lysosomal degradation of host protein; VP4-induced degradation of NME1 through the macroautophagy pathway, and impaired p53-mediated signaling. p53 plays significant roles in antiviral innate immunity by inducing several interferon-inducible antiviral genes expression, such as, ISG20, IRF9, RIG-I, and ISG15. VP4 promoted interaction of p53 with murine double minute 2 (MDM2) through downregulation of NME1 resulting in destabilization of p53. Therefore, 5-flurouracil-induced upregulation of ISG20, IRF9, RIG-I, and ISG15 were suppressed by VP4. VP4-induced reduction of NME1 was not related to the well-characterized blocking effect of FMDV on cellular translation, and no direct interaction was detected between NME1 and VP4. The 15–30 and 75–85 regions of VP4 were determined to be crucial for VP4-induced reduction of NME1. Deletion of these VP4 regions also inhibited the suppressive effect of VP4 on NME1-enhanced p53 signaling. In conclusion, these data suggest an antiviral role of NME1 by regulation of p53-mediated antiviral innate immunity in virus-infected cells, and reveal an antagonistic mechanism of FMDV that is mediated by VP4 to block host innate immune antiviral response.
Optimal dynamic coding by mixed-dimensionality neurons in the head-direction system of bats
Authors: Finkelstein Arseny , Ulanovsky Nachum , Tsodyks Misha , Aljadeff Johnatan 
Published: August 2018

AbstractEthologically relevant stimuli are often multidimensional. In many brain systems, neurons with “pure” tuning to one stimulus dimension are found along with “conjunctive” neurons that encode several dimensions, forming an apparently redundant representation. Here we show using theoretical analysis that a mixed-dimensionality code can efficiently represent a stimulus in different behavioral regimes: encoding by conjunctive cells is more robust when the stimulus changes quickly, whereas on long timescales pure cells represent the stimulus more efficiently with fewer neurons. We tested our predictions experimentally in the bat head-direction system and found that many head-direction cells switched their tuning dynamically from pure to conjunctive representation as a function of angular velocity—confirming our theoretical prediction. More broadly, our results suggest that optimal dimensionality depends on population size and on the time available for decoding—which might explain why mixed-dimensionality representations are common in sensory, motor, and higher cognitive systems across species.
Non-Abelian adiabatic geometric transformations in a cold strontium gas
Authors: Leroux F. , Pandey K. , Rehbi R. , Chevy F. , Miniatura C. , Grémaud B. , Wilkowski D. 
Published: August 2018

AbstractTopology, geometry, and gauge fields play key roles in quantum physics as exemplified by fundamental phenomena such as the Aharonov–Bohm effect, the integer quantum Hall effect, the spin Hall, and topological insulators. The concept of topological protection has also become a salient ingredient in many schemes for quantum information processing and fault-tolerant quantum computation. The physical properties of such systems crucially depend on the symmetry group of the underlying holonomy. Here, we study a laser-cooled gas of strontium atoms coupled to laser fields through a four-level resonant tripod scheme. By cycling the relative phases of the tripod beams, we realize non-Abelian SU(2) geometrical transformations acting on the dark states of the system and demonstrate their non-Abelian character. We also reveal how the gauge field imprinted on the atoms impact their internal state dynamics. It leads to a thermometry method based on the interferometric displacement of atoms in the tripod beams.
Atomic force microscopy methodology and AFMech Suite software for nanomechanics on heterogeneous soft materials
Authors: Galluzzi Massimiliano , Tang Guanlin , Biswas Chandra S. , Zhao Jinlai , Chen Shiguo , Stadler Florian J. 
Published: August 2018

AbstractAtomic force microscopy has proven to be a valuable technique to characterize the mechanical and morphological properties of heterogeneous soft materials such as biological specimens in liquid environment. Here we propose a 3-step method in order to investigate biological specimens where heterogeneity hinder a quantitative characterization: (1) precise AFM calibration, (2) nano-indentation in force volume mode, (3) array of finite element simulations built from AFM indentation events. We combine simulations to determine internal geometries, multi-layer material properties, and interfacial friction. In order to easily perform this analysis from raw AFM data to simulation comparison, we propose a standalone software, AFMech Suite comprising five interacting interfaces for simultaneous calibration, morphology, adhesion, mechanical, and simulation analysis. We test the methodology on soft hydrogels with hard spherical inclusions, as a soft-matter model system. Finally, we apply the method on E. coli bacteria supported on soft/hard hydrogels to prove usefulness in biological field.
Adipocyte hypertrophy and lipid dynamics underlie mammary gland remodeling after lactation
Authors: Zwick Rachel K. , Rudolph Michael C. , Shook Brett A. , Holtrup Brandon , Roth Eve , Lei Vivian , Van Keymeulen Alexandra , Seewaldt Victoria , Kwei Stephanie , Wysolmerski John , Rodeheffer Matthew S. , Horsley Valerie 
Published: August 2018

AbstractAdipocytes undergo pronounced changes in size and behavior to support diverse tissue functions, but the mechanisms that control these changes are not well understood. Mammary gland-associated white adipose tissue (mgWAT) regresses in support of milk fat production during lactation and expands during the subsequent involution of milk-producing epithelial cells, providing one of the most marked physiological examples of adipose growth. We examined cellular mechanisms and functional implications of adipocyte and lipid dynamics in the mouse mammary gland (MG). Using in vivo analysis of adipocyte precursors and genetic tracing of mature adipocytes, we find mature adipocyte hypertrophy to be a primary mechanism of mgWAT expansion during involution. Lipid tracking and lipidomics demonstrate that adipocytes fill with epithelial-derived milk lipid. Furthermore, ablation of mgWAT during involution reveals an essential role for adipocytes in milk trafficking from, and proper restructuring of, the mammary epithelium. This work advances our understanding of MG remodeling and tissue-specific roles for adipocytes.
Land use driven change in soil pH affects microbial carbon cycling processes
Authors: Malik Ashish A. , Puissant Jeremy , Buckeridge Kate M. , Goodall Tim , Jehmlich Nico , Chowdhury Somak , Gweon Hyun Soon , Peyton Jodey M. , Mason Kelly E. , van Agtmaal Maaike , Blaud Aimeric , Clark Ian M. , Whitaker Jeanette , Pywell Richard F. , Ostle Nick , Gleixner Gerd , Griffiths Robert I. 
Published: August 2018

AbstractSoil microorganisms act as gatekeepers for soil–atmosphere carbon exchange by balancing the accumulation and release of soil organic matter. However, poor understanding of the mechanisms responsible hinders the development of effective land management strategies to enhance soil carbon storage. Here we empirically test the link between microbial ecophysiological traits and topsoil carbon content across geographically distributed soils and land use contrasts. We discovered distinct pH controls on microbial mechanisms of carbon accumulation. Land use intensification in low-pH soils that increased the pH above a threshold (~6.2) leads to carbon loss through increased decomposition, following alleviation of acid retardation of microbial growth. However, loss of carbon with intensification in near-neutral pH soils was linked to decreased microbial biomass and reduced growth efficiency that was, in turn, related to trade-offs with stress alleviation and resource acquisition. Thus, less-intensive management practices in near-neutral pH soils have more potential for carbon storage through increased microbial growth efficiency, whereas in acidic soils, microbial growth is a bigger constraint on decomposition rates.
Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq
Authors: Karaayvaz Mihriban , Cristea Simona , Gillespie Shawn M. , Patel Anoop P. , Mylvaganam Ravindra , Luo Christina C. , Specht Michelle C. , Bernstein Bradley E. , Michor Franziska , Ellisen Leif W. 
Published: August 2018

AbstractTriple-negative breast cancer (TNBC) is an aggressive subtype characterized by extensive intratumoral heterogeneity. To investigate the underlying biology, we conducted single-cell RNA-sequencing (scRNA-seq) of >1500 cells from six primary TNBC. Here, we show that intercellular heterogeneity of gene expression programs within each tumor is variable and largely correlates with clonality of inferred genomic copy number changes, suggesting that genotype drives the gene expression phenotype of individual subpopulations. Clustering of gene expression profiles identified distinct subgroups of malignant cells shared by multiple tumors, including a single subpopulation associated with multiple signatures of treatment resistance and metastasis, and characterized functionally by activation of glycosphingolipid metabolism and associated innate immunity pathways. A novel signature defining this subpopulation predicts long-term outcomes for TNBC patients in a large cohort. Collectively, this analysis reveals the functional heterogeneity and its association with genomic evolution in TNBC, and uncovers unanticipated biological principles dictating poor outcomes in this disease.