bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes to the Water Balance Over a Century of Urban Development in Two Neighborhoods: Vancouver, Canada
Authors: Kokkonen T. V. , Grimmond C. S. B. , Christen A. , Oke T. R. , Järvi L.
Published: August 2018

Hydrological cycles of two suburban neighborhoods in Vancouver, BC, during initial urban development and subsequent urban densification (1920–2010) are examined using the Surface Urban Energy and Water Balance Scheme. The two neighborhoods have different surface characteristics (as determined from aerial photographs) which impact the hydrological processes. Unlike previous studies of the effect of urbanization on the local hydrology, densification of already built lots is explored with a focus on the neighborhood scale. Human behavioral changes to irrigation are accounted for in the simulations. Irrigation is the dominant factor, accounting for up to 56% of the water input on an annual basis in the study areas. This may surpass garden needs and go to runoff. Irrigating once a week would provide sufficient water for the garden. Without irrigation, evaporation would have decreased over the 91 years at a rate of up to 1.4 mm/year and runoff increased at 4.0 mm/year with the increase in impervious cover. Similarly without irrigation, the ratio of sensible heat flux to the available energy would have increased over the 91 years at a rate of up to 0.003 per year. Urbanization and densification cause an increase in runoff and increase risk of surface flooding. Small daily runoff events with short return periods have increased over the century, whereas the occurrence of heavy daily runoff events (return period > 52 days) are not affected. The results can help us to understand the dominant factors in the suburban hydrological cycle and can inform urban planning.
Searching for Signs of Marsquakes
Authors: Wheeling Kate
Published: August 2018

Researchers use high-resolution images of Mars’s surface to look for signals of coseismic displacement.
U‐PB Detrital Zircon Geochronology of the Lower Danube and Its Tributaries: Implications for the Geology of the Carpathians
Authors: Ducea Mihai N. , Giosan Liviu , Carter Andrew , Balica Constantin , Stoica Adriana M. , Roban Relu D. , Balintoni Ion , Filip Florin , Petrescu Lucian
Published: August 2018

We performed a detrital zircon (DZ) U‐Pb geochronologic survey of the lower parts of the Danube River approaching its Danube delta, Black Sea sink, and a few large tributaries (Tisza, Jiu, Olt, and Siret) originating in the nearby Carpathian Mountains. Samples are modern sediments. DZ age spectra reflect the geology and specifically the crustal age formation of the source area, which in this case is primarily the Romanian Carpathians and their foreland with contributions from the Balkan Mountains to the south of Danube and the East European Craton. The zircon cargo of these rivers suggests a source area that formed during the latest Proterozoic and mostly into the Cambrian and Ordovician as island arcs and back‐arc basins in a Peri‐Gondwanan subduction setting (~600–440 Ma). The Inner Carpathian units are dominated by a U‐Pb DZ peak in the Ordovician (460–470 Ma) and little inheritance from the nearby continental masses, whereas the Outer Carpathian units and the foreland have two main peaks, one Ediacaran (570–610 Ma) and one in the earliest Permian (290–300 Ma), corresponding to granitic rocks known regionally. A prominent igneous Variscan peak (320–350 Ma) in the Danube's and tributaries DZ zircon record is difficult to explain and points out to either an extra Carpathian source or major unknown gaps in our understanding of Carpathian geology. Younger peaks corresponding to arc magmatism during the Alpine period make up as much as about 10% of the DZ archive, consistent with the magnitude and surface exposure of Mesozoic and Cenozoic arcs.
Local Excitation of Whistler Mode Waves and Associated Langmuir Waves at Dayside Reconnection Regions
Authors: Li Jinxing , Bortnik Jacob , An Xin , Li Wen , Russell Christopher T. , Zhou Meng , Berchem Jean , Zhao Cong , Wang Shan , Torbert Roy B. , Le Contel Olivier , Ergun Robert E. , Lindqvist Per‐Arne , Pollock Craig J. , Burch James L.
Published: August 2018

In the Earth's dayside reconnection boundary layer, whistler mode waves coincide with magnetic field openings and the formation of the resultant anisotropic electrons. Depending on the energy range of anisotropic electrons, whistlers can grow at frequencies in the upper and/or lower band. Observations show that whistler mode waves modulate Langmuir wave amplitude as they propagate toward the X line. Observations of whistler mode wave phase and Langmuir waves packets, as well as coincident electron measurements, reveal that whistler mode waves can accelerate electrons via Landau resonance at locations where E||is antiparallel to the wave propagation direction. The accelerated electrons produce localized beams, which subsequently drive the periodically modulated Langmuir waves. The close association of those two wave modes reveals the microscale electron dynamics in the exhaust region, and the proposed mechanism could potentially be applied to explain the modulation events observed in planetary magnetospheres and in the solar wind.
Reversal of the Direction of Horizontal Velocities Induced by GIA as a Function of Mantle Viscosity
Authors: Hermans T. H. J. , van der Wal W. , Broerse T.
Published: August 2018

In regions undergoing glacial isostatic adjustment present‐day horizontal surface motion is observed to point mostly, but not always, away from the former ice load. To interpret these observations, we investigate the direction of horizontal velocities using glacial isostatic adjustment models. The direction is controlled by the opposing actions of inward mantle flow and outward lithosphere motion. In contrast with the prevailing idea that glacial isostatic adjustment‐induced horizontal velocities point outward, we show that velocities can be either outward or inward. Immediately after deglaciation velocities point inward but change direction to outward after a time that is controlled by mantle viscosity. Present‐day horizontal velocities point outward for a uniform mantle viscosity below 1020 Pa s and inward for above 1022 Pa s, with a combination of outward and inward in between. Our results help to interpret GPS‐observed horizontal velocities in areas with varying mantle viscosity.
First Evidence of Persistent Nighttime Temperature Structures in the Neutral Thermosphere of Mars
Authors: Pilinski M. , Bougher S. , Greer K. , Thiemann E. , Andersson L. , Benna M. , Elrod M.
Published: August 2018

Using two Mars years of data collected by the Neutral Gas and Ion Mass Spectrometer on the Mars Atmosphere and Volatiles EvolutioN spacecraft, we reconstruct the local solar time structure of the Martian equatorial thermosphere for the dawn and dusk sectors. The results indicate the presence of several persistent features near the dusk and dawn terminators appearing in the neutral temperature and in the O, Ar, N2, and CO2 densities. The dusk temperature features include a minimum at the terminator surrounded by two local maxima with amplitudes between 20 and 40 K. A nighttime temperature enhancement occurs at a local solar time of 4–5 hr and has an amplitude between 50 and 100 K relative to the surrounding temperatures. The observed enhancements are interpreted to be a result of either nighttime dynamical heating caused by converging and downwelling winds or of a terminator wave originating in the lower atmosphere.
Spatial Heterogeneity of the Temporal Dynamics of Arctic Tundra Vegetation
Authors: Reichle L. M. , Epstein H. E. , Bhatt U. S. , Raynolds M. K. , Walker D. A.
Published: August 2018

Arctic tundra vegetation has largely been “greening” in recent decades, resulting in major changes to terrestrial ecosystems, with implications for surface energy balance, permafrost, carbon and water cycling, herbivore populations, and human land use. While general greening trends have been well‐studied, more specific vegetation‐temperature dynamics are spatially and temporally heterogeneous and currently not well understood. This study uses Normalized Difference Vegetation Index (NDVI) and Summer Warmth Index (SWI) data to investigate patterns of arctic tundra vegetation and temperature dynamics over North American and Eurasian continents and by Arctic bioclimate subzones (essentially latitudinal‐based). Relative vegetation increases in northern subzones were muted compared to temperature increases, whereas relative vegetation increases in southern subzones were consistent with, or greater than, relative temperature changes. Detrended, interannual NDVI variances were greatest in middle and southern subzones, whereas interannual SWI variances were greatest in southern subzones. Annual SWI and NDVI relationships were strongest in midlatitude subzones.
Response of Banded Whistler Mode Waves to the Enhancement of Solar Wind Dynamic Pressure in the Inner Earth's Magnetosphere
Authors: Yu Xiongdong , Yuan Zhigang , Li Haimeng , Huang Shiyong , Wang Dedong , Yao Fei , Funsten H. O. , Wygant J. R.
Published: August 2018

With observations of Van Allen Probe A, in this letter we display a typical event where banded whistler waves shifted up their frequencies with frequency bands broadening as a response to the enhancement of solar wind dynamic pressure. Meanwhile, the anisotropy of electrons with energies about several tens of keV was observed to increase. Through the comparison of the calculated wave growth rates and observed wave spectral intensity, we suggest that those banded whistler waves observed with frequencies shifted up and frequency bands broadening could be locally excited by these hot electrons with increased anisotropy. The current study provides a great in situ evidence for the influence on frequencies of banded whistler waves by the enhancement of solar wind dynamic pressures, which reveals the important role of solar wind dynamic pressures playing in the frequency properties of banded whistler waves.
Energy Conversion Reveals Regime Transition of Imbibition in a Rough Fracture
Authors: Hu Ran , Wu Dong‐Sheng , Yang Zhibing , Chen Yi‐Feng
Published: August 2018

As externally imposed flow rate increases during imbibition, viscous force increasingly dominates displacement over capillarity and imbibition shifts from capillary to capillary‐viscous regimes. Previous studies focused on capillary regime, lacking a fundamental understanding of regime transition. Here we study the imbibition transition via flow rate‐controlled experiments in a rough fracture. By analyzing energy balance in multiphase flow system, we find a fundamental link between regime transition and energy conversion. In capillary regime, surface energy is partially transformed into external work and an amount of 51−58% is dissipated via local rapid, irreversible events; while in capillary‐viscous regime, surface energy together with external work is transformed into kinetic and dissipated energies. This transition, corresponding to critical capillary number, is evidenced by quantitative analysis of invasion morphologies. Our work bridges the gap between energy conversion/dissipation and multiphase flow and has important implications for identifying imbibition regimes in enhanced oil recovery and geological CO2 sequestration.
Western Pacific Oceanic Heat Content: A Better Predictor of La Niña Than of El Niño
Authors: Planton Yann , Vialard Jérôme , Guilyardi Eric , Lengaigne Matthieu , Izumo Takeshi
Published: August 2018

The western equatorial Pacific oceanic heat content (warm water volume in the west or WWVw) is the best El Niño–Southern Oscillation (ENSO) predictor beyond 1‐year lead. Using observations and selected Coupled Model Intercomparison Project Phase 5 simulations, we show that a discharged WWVw in boreal fall is a better predictor of La Niña than a recharged WWVw for El Niño 13 months later, both in terms of occurrence and amplitude. These results are robust when considering the heat content across the entire equatorial Pacific (WWV) at shorter lead times, including all Coupled Model Intercomparison Project Phase 5 models or excluding Niño‐Niña and Niña‐Niño phase transitions. Suggested mechanisms for this asymmetry include (1) the negatively skewed WWVw distribution with stronger discharges related to stronger wind stress anomalies during El Niño and (2) the stronger positive Bjerknes feedback loop during El Niño. The possible role of stronger subseasonal wind variations during El Niño is also discussed.
A Comparison of Quiet Time Thermospheric Winds Between FPI Observations and Model Calculations
Authors: Jiang Guoying , Xu Jiyao , Wang Wenbin , Yuan Wei , Zhang Shunrong , Yu Tao , Zhang Xiaoxin , Huang Cong , Kerr Robert B. , Noto John , Li Jingyuan , Liu Weijun , Li Qinzeng
Published: August 2018

We investigate local time, seasonal, and longitudinal variations of thermospheric horizontal winds at midlatitudes during geomagnetically quiet times by comparing winds from observations, an empirical wind model, and a numerical model. The observations are from three Fabry‐Perot interferometers (FPIs), the empirical model is the most recent version of the Horizontal Wind Model 14 (HWM14), and the numerical model is the Thermosphere‐Ionosphere‐Electrodynamics General Circulation Model of the National Center for Atmospheric Research. The three FPI stations are located at Xinglong (geographically 40.2°N, 117.4°E; geomagnetically 35°N) and Kelan (geographically 38.7°N, 111.6°E; geomagnetically 34°N) in China and at Millstone Hill (geographically 42.6°N, 71.5°W; geomagnetically 52°N) in United States. The results show that the winds at Millstone Hill are more southward and more westward than those at Xinglong and Kelan in all seasons; the directional reversal time of zonal winds is also earlier at Millstone Hill than at the other two stations. Thermosphere‐Ionosphere‐Electrodynamics General Circulation Model shows better agreement with FPI observations in the winter months compared to summer, and in general best replicates those measurements taken at Millstone Hill. HWM14 generally produces agreement with quiet time midlatitude neutral wind measurements, with HWM14 meridional winds comparing very well throughout most of a year. HWM14 model‐data discrepancies occur mainly in the zonal winds during the winter season. Overall, HWM14 predicts MH FPI observations slightly better than it does for the data from the two Asian stations.
Polar Ion Temperature Variations During the 22 January 2012 Magnetic Storm
Authors: Horvath Ildiko , Lovell Brian C.
Published: August 2018

We study the 22 January 2012 magnetic storm, during which some localized neutral density (DN) increases developed, and its polar ion temperature (Ti) variations in terms of the earthward Poynting flux (S||) deposited into the coupled ionosphere‐thermosphere system. We investigate the storm's nature, some flow channel events that are the ionospheric signatures of flux transfer events triggered by magnetic reconnections, and the resultant thermospheric responses. We utilize solar and interplanetary magnetic field data and multi‐instrument topside ionospheric and thermospheric measurements. Results reveal the presence of antisunward propagating solar wind Alfven waves during the various storm phases triggering flux transfer events/flow channel events and launching atmospheric gravity waves whose Ti signatures appeared as episodic Ti variations. Various scenarios demonstrate the direct correlation between S|| and DN and the irregular Ti responses within/above flow channels that we explain in terms of frictional heating (Tfrc). We identify Ti responses during various flow channel events as (1) direct/intermittent and (2) opposite, with S|| and DN reflecting the respective underlying flow channel development at the time of detection as (1) early stage when Tfrc was high due to the still large velocity differences between ions and neutrals and as (2) late stage when Tfrc ceased since ions and neutrals moved together. Ti oscillations are observed to be originating from polar or auroral flow channels and propagating across the polar cap toward the equator. We conclude that antisunward solar wind Alfven waves had a significant impact on Ti variability during this storm by modulating magnetic reconnection and launching atmospheric gravity waves.
Recurring Slow Slip Events and Earthquake Nucleation in the Source Region of the M 7 Ibaraki‐Oki Earthquakes Revealed by Earthquake Swarm and Foreshock Activity
Authors: Nishikawa Tomoaki , Ide Satoshi
Published: August 2018

Slow slip events (SSEs) on the plate interface are closely related to the occurrence of earthquakes and often trigger earthquake swarms in subduction zones. Moreover, some SSEs, accompanied by intensive foreshocks, precede large interplate earthquakes. Therefore, detecting and monitoring SSEs is important for assessing the potential of future large earthquakes. However, there are many SSEs not followed by large earthquakes, and it is unclear whether these can be distinguished from SSEs preceding large earthquakes. Here we use the epidemic‐type aftershock sequence (ETAS) model and matched‐filter technique to examine the spatial‐temporal distribution of earthquake swarms and foreshocks at Ibaraki‐Oki in the Japan Trench. We found that 19 swarm sequences repeatedly occurred during the period 1982–2008 at the same location as the foreshock sequences of the 1982 and 2008 M 7 Ibaraki‐Oki earthquakes. Both the foreshock and swarm sequences contain repeating earthquakes and have anomalously high seismicity rates inexplicable by the ETAS model, suggesting the recurrence of SSEs. The foreshock sequences in 1982 and 2008 contain more events inexplicable by the ETAS model than the swarm sequences. The fault slip of repeating earthquakes in the 2008 foreshock sequence was also larger than those of the swarm sequences, and the slip rate showed an abrupt increase 12 hr before the 2008 M 7 event. Our results imply that the SSEs that preceded the M 7 events had larger seismic moments than the other SSEs. These large SSEs might be related to the nucleation phase of the M 7 earthquakes.
Estimating Hypoxic Volume in the Chesapeake Bay Using Two Continuously Sampled Oxygen Profiles
Authors: Bever Aaron J. , Friedrichs Marjorie A. M. , Friedrichs Carl T. , Scully Malcolm E.
Published: August 2018

Low levels of dissolved oxygen (DO) occur in many embayments throughout the world and have numerous detrimental effects on biota. Although measurement of in situ DO is straightforward with modern instrumentation, quantifying the volume of water in a given embayment that is hypoxic (hypoxic volume (HV)) is a more difficult task; however, this information is critical for determining whether management efforts to increase DO are having an overall impact. This paper uses output from a three‐dimensional numerical model to demonstrate that HV in Chesapeake Bay can be estimated well with as few as two vertical profiles. In addition, the cumulative hypoxic volume (HVC; the total amount of hypoxia in a given year) can be calculated with relatively low uncertainty (<10%) if continuous DO data are available from two strategically positioned vertical profiles. This is because HV in the Chesapeake Bay is strongly constrained by the geometry of the embayment. A simple Geometric HV calculation method is presented and numerical model results are used to illustrate that for calculating HVC, the results using two daily‐averaged profiles are typically more accurate than those of the standard method that interpolates bimonthly cruise data. Bimonthly data produce less accurate estimates of HVC because high‐frequency changes in oxygen concentration, for example, due to regional‐weather‐ or storm‐induced changes in wind direction and magnitude, are not resolved. The advantages of supplementing cruise‐based sampling with continuous vertical profiles to estimate HVC should be applicable to other systems where hypoxic water is constrained to a specific area by bathymetry.
Thank You to Our 2017 Peer Reviewers
Authors: Brewer Peter , Chambers Don , Hetland Robert , Karnauskas Kristopher , Lowe Ryan , Moran S. Bradley , Oey Lie‐Yauw , Pinardi Nadia , Proshutinsky Andrey
Published: August 2018

Similar to the construction of physical ships and laboratory buildings, scientific knowledge is built incrementally and requires solid components of data, theory, and methodology at each phase of the “construction.” The peer‐review process provides the necessary “inspection” and the assurance that every step of the construction is solid, particularly in regard to the proper use of the scientific method. The peer‐review process helps improve the published work by providing constructive suggestions and by safeguarding against scientific work that could later be found to be built on shaky foundations. Because no single scientist has intimate knowledge of today's many aspects of the Ocean Sciences, we rely on each other's expertise to serve as unbiased “inspectors” of published articles. Your considerable time and effort, spent reviewing JGR‐Oceans manuscript(s) during 2017, are sincerely appreciated by our editorial board and by the Ocean Science community at large. We thank you for rising to this professional challenge and for your wisdom, commitment, skill, and service.
Modeling Regional Pollution Transport Events During KORUS‐AQ: Progress and Challenges in Improving Representation of Land‐Atmosphere Feedbacks
Authors: Huang Min , Crawford James H. , Diskin Glenn S. , Santanello Joseph A. , Kumar Sujay V. , Pusede Sally E. , Parrington Mark , Carmichael Gregory R.
Published: August 2018

This study evaluates the impact of assimilating soil moisture data from National Aeronautics and Space Administration (NASA)'s Soil Moisture Active Passive (SMAP) on short‐term regional weather and air quality modeling in East Asia during the Korea‐U.S. Air Quality Study (KORUS‐AQ) airborne campaign. SMAP data are assimilated into the Noah land surface model using an ensemble Kalman filter approach in the Land Information System framework, which is semicoupled with the NASA‐Unified Weather Research and Forecasting model with online chemistry (NUWRF‐Chem). With SMAP assimilation included, water vapor and carbon monoxide (CO) transport from northern central China transitional climate zones to South Korea is better represented in NUWRF‐Chem during two studied pollution events. Influenced by different synoptic conditions and emission patterns, impact of SMAP assimilation on modeled CO in South Korea is intense (>30 ppbv) during one event and less significant (<8 ppbv) during the other. SMAP assimilation impact on air quality modeling skill is complicated by other error sources such as the chemical initial and boundary conditions (IC/LBC) and emission inputs of NUWRF‐Chem. Using a satellite‐observation‐constrained chemical IC/LBC instead of a free‐running, coarser‐resolution chemical IC/LBC reduces modeled CO by up to 80 ppbv over South Korea. Consequently, CO performance is improved in the middle‐upper troposphere whereas degraded in the lower troposphere. Remaining negative CO biases result largely from the emissions inputs. The advancements in land surface modeling and chemical IC/LBC presented here are expected to benefit future investigations on constraining emissions using observations, which can in turn enable more accurate assessments of SMAP assimilation and chemical IC/LBC impacts.
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

Satellite 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

Renal 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

Bone 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

Pin1 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

Radiotherapy 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

To 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

Aberrant 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

Necroptosis 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

Nucleoside 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

Ethologically 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

Topology, 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

Atomic 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

Adipocytes 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

Soil 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

Triple-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.
Expression and Manipulation of the APC-β-Catenin Pathway During Peripheral Neuron Regeneration
Authors: Duraikannu Arul , Martinez Jose A. , Chandrasekhar Ambika , Zochodne Douglas W.
Published: August 2018

Molecules and pathways that suppress growth are expressed in postmitotic neurons, a potential advantage in mature neural networks, but a liability during regeneration. In this work, we probed the APC (adenomatous polyposis coli)-β-catenin partner pathway in adult peripheral sensory neurons during regeneration. APC had robust expression in the cytoplasm and perinuclear region of adult DRG sensory neurons both before and after axotomy injury. β-catenin was expressed in neuronal nuclei, neuronal cytoplasm and also in perineuronal satellite cells. In injured dorsal root ganglia (DRG) sensory neurons and their axons, we observed paradoxical APC upregulation, despite its role as an inhibitor of growth whereas β-catenin was downregulated. Inhibition of APC in adult sensory neurons and activation of β-catenin, LEF/TCF transcriptional factors were associated with increased neuronal plasticity in vitro. Local knockdown of APC, at the site of sciatic nerve crush injury enhanced evidence for electrophysiological, behavioural and structural regeneration in vivo. This was accompanied by upregulation of β-catenin. Collectively, the APC-β-catenin-LEF/TCF transcriptional pathway impacts intrinsic mechanisms of axonal regeneration and neuronal plasticity after injury, offering new options for addressing axon regeneration.