bluuebunny/crossref_metadata_2025 huggingface dataset:
Space‐Time Evolution of Greenland Ice Sheet Elevation and Mass From Envisat and GRACE Data
Authors: Yang Yuande , Li Fei , Hwang Cheinway , Ding Minghu , Ran Jiangjun
Published: July 2019

Precise measurements of height changes (HCs) are important for improved estimates of mass balance of the Greenland Ice Sheet (GrIS). Here we determine 10 years of precise, high‐resolution HCs of the GrIS from Envisat radar altimeter using a subwaveform retracker and a modified repeat‐track method. The HCs show clear seasonal changes and monotonic declines over glaciers on the coasts such as Zachariae Isstrøm. We enhance mass change estimates from Gravity Recovery and Climate Experiment (GRACE) data using HCs and densities from interannual correlations between GRACE‐derived mass changes and HCs. We estimate the mass changes of eight drainage basins with our combined mass change. The largest mass change between 2002 and 2012 occurred in the northwest basin and the smallest in the northeast basin. We separate the ice and snow HC rates to derive a ratio (f) between them to characterize the relative importance of ice or snow to mass change. The snow HC rates are mostly positive over the GrIS, except on the margins of the west coast and Zachariae Isstrøm. The mean ice HC rate is −6.6 ± 3.9 cm/year over 2002–2006, which accelerated to −13.9 ± 2.4 cm/year over 2007–2012. The f factors show a clear post‐2006 ice dominance in the GrIS mass loss, particularly on the west coast, with a mean 91.4% ice contribution over 2002–2006, increasing to 94.5% over 2007–2012. This indicates increasing mass loss after 2006. A coincident radar altimeter and gravimetry mission is important for studying mass balance and separating snow and ice contributions over space and time.
Nutrient Controls on Export Production in the Southern Ocean
Authors: Arteaga Lionel A. , Pahlow Markus , Bushinsky Seth M. , Sarmiento Jorge L.
Published: July 2019

We use observations from novel biogeochemical profiling floats deployed by the Southern Ocean Carbon and Climate Observations and Modeling program to estimate annual net community production (ANCP; associated with carbon export) from the seasonal drawdown of mesopelagic oxygen and surface nitrate in the Southern Ocean. Our estimates agree with previous observations in showing an increase in ANCP in the vicinity of the polar front (∼3 mol C m−2 y−1), compared to lower rates in the subtropical zone (≤ 1 mol C m−2 y−1) and the seasonal ice zone (<2 mol C m−2 y−1). Paradoxically, the increase in ANCP south of the subtropical front is associated with elevated surface nitrate and silicate concentrations, but decreasing surface iron. We hypothesize that iron limitation promotes silicification in diatoms, which is evidenced by the low silicate to nitrate ratio of surface waters around the Antarctic polar front. High diatom silicification increases the ballasting effect of particulate organic carbon and overall ANCP in this region. A model‐based assessment of our methods shows a good agreement between ANCP estimates based on oxygen and nitrate drawdown and the modeled downward organic carbon flux at 100 m. This agreement supports the presumption that net biological consumption is the dominant process affecting the drawdown of these chemical tracers and that, given sufficient data, ANCP can be inferred from observations of oxygen and/or nitrate drawdown in the Southern Ocean.
Constitutive Laws for Etnean Basement and Edifice Lithologies
Authors: Bakker Richard R. , Violay Marie E. S. , Vinciguerra Sergio , Fazio Marco , Benson Philip M.
Published: July 2019

The mechanical dynamics of volcanic systems can be better understood with detailed knowledge on strength of a volcanic edifice and subsurface. Previous work highlighting this on Mt. Etna has suggested that its carbonate basement could be a significant zone of widespread planar weakness. Here, we report new deformation experiments to better quantify such effects. We measure and compare key deformation parameters using Etna basalt, which is representative of upper edifice lava flows, and Comiso limestone, which is representative of the carbonate basement, under upper crustal conditions. These data are then used to derive empirical constitutive equations describing changes in rocks strength with pressure, temperature, and strain rate. At a constant strain rate of 10‐5 s‐1 and an applied confining pressure of 50 MPa, the brittle‐to‐ductile transitions were observed at 975 °C (Etna basalt) and 350 °C (Comiso limestone). For the basaltic edifice of Mt. Etna, the strength is described with a Mohr‐Coulomb failure criterion with μ ~ 0.704, C = 20 MPa. For the carbonate basement, strength is best described by a power law‐type flow in two regimes: a low‐T regime with stress exponent n ~ 5.4 and an activation energy Q ~ 170.6 kJ/mol and a high‐T regime with n ~ 2.4 and Q ~ 293.4 kJ/mol. We show that extrapolation of these data to Etna's basement predicts a brittle‐to‐ductile transition that corresponds well with the generally observed trends of the seismogenic zone underneath Mt. Etna. This in turn may be useful for future numerical simulations of volcano‐tectonic deformation of Mt. Etna, and other volcanoes with limestone basements.
Viscoplastic Interpretation of Localized Compaction Creep in Porous Rock
Authors: Shahin Ghassan , Marinelli Ferdinando , Buscarnera Giuseppe
Published: July 2019

Recent laboratory evidence shows that compaction creep in porous rocks may develop through stages of acceleration, especially if the material is susceptible to strain localization. This paper provides a mechanical interpretation of compaction creep based on viscoplasticity and nonlinear dynamics. For this purpose, a constitutive operator describing the evolution of compaction creep is defined to evaluate the spontaneous accumulation of pore collapse within an active compaction band. This strategy enables the determination of eigenvalues associated with the stability of the response which is able to differentiate decelerating from accelerating strain. This mathematical formalism was linked to a constitutive law able to simulate compaction localization. Material point simulations were then used to identify the region of the stress space where unstable compaction creep is expected, showing that accelerating strains correspond to pulses of inelastic strain rate. Such pulses were also found in full‐field numerical analyses of delayed compaction, revealing that they correspond to stages of inception and propagation of new bands across the volume of the simulated sample. These results illustrate the intimate relation between the spatial patterns of compaction and their temporal dynamics, showing that while homogeneous compaction develops with decaying rates of accumulation, localized compaction occurs through stages of accelerating deformation caused by the loss of strength taking place during the formation of a band. In addition, they provide a predictive modeling framework to simulate and explain the spatio‐temporal dynamics of compaction in porous sedimentary formations.
Global Soil Moisture‐Air Temperature Coupling Based on GRACE‐Derived Terrestrial Water Storage
Authors: Chen Ajiao , Guan Huade , Batelaan Okke , Zhang Xinping , He Xinguang
Published: July 2019

Understanding global soil moisture‐air temperature (θ‐Ta) coupling is needed to improve the representation of land‐atmosphere interactions in Earth system models. Most studies on θ‐Ta coupling have focused on hot extremes, where precipitation‐related indices and model‐derived soil moisture products are commonly used. In this study, global θ‐Ta coupling is examined based on monthly air temperature anomalies and the Gravity Recovery and Climate Experiment (GRACE) terrestrial water storage (TWS). A discrete wavelet decomposition is used to partition the TWS into different components. The results show that TWS is useful in revealing the spatial patterns of θ‐Ta coupling. Decomposed GRACE TWS shows improved skill compared to raw TWS in explaining temporal variability of monthly air temperature, which likely reflects different roles of soil moisture at different depths in the θ‐Ta coupling. The explanatory power improves further by using a combination of decomposed GRACE TWS and precipitation. Such improvement is observed particularly in places where vegetation tends to have a deeper rooting system, such as eastern region of South America, the southern tip of Africa, and north of the Tropic of Capricorn in Australia. The occurrence of θ‐Ta coupling is mainly constrained by the coupling of root zone moisture and land surface temperature. In addition to deeper rooting systems, clear wet and dry season alternation is another favorable factor for developing significant monthly θ‐Ta coupling.
Landscape Response to Lateral Advection in Convergent Orogens Over Geologic Time Scales
Authors: Eizenhöfer Paul R. , McQuarrie Nadine , Shelef Eitan , Ehlers Todd A.
Published: July 2019

Convergent orogens exhibit high elevations and relief, features characteristic of active rock uplift, the latter influencing normalized channel steepness (Ksn). In systems with significant horizontal displacement, Ksn values and interfluves are elevated over a region of tens of kilometers and gradually decline in the direction of rock advection. To evaluate potential relationships between elevated Ksn, a gradual decline in interfluve elevation (i.e., tapered topography), and lateral advection, we integrated kinematic models that simulate advection over a midcrustal ramp with a 2‐D surface processes model. Varying convergence rate, bedrock erodibility, and ramp angle, we tracked topographic evolution over time. The process of advection through the region of active rock uplift above a midcrustal ramp is preserved in the geomorphic record through transient legacy landscapes characterized by (i) high‐relief, advection‐parallel interfluves, (ii) tapered topography, (iii) elevated and gradually declining Ksn values, and (iv) higher Ksn in trunk relative to tributary streams likely reflecting the influence of increased sediment flux, elevated interfluves, and changes in drainage area. The width of legacy landscapes provides a minimum constraint on the total lateral displacement, controlled by the duration of ramp activity and the rates of advection and erosion. The development of legacy landscapes is facilitated by spatial variations in flow convergence that occur in a 2‐D setting but are not captured in idealized 1‐D approaches. The presence of elevated Ksn and high relief, advection‐parallel interfluves beyond the region of active rock uplift likely reflects the horizontal advection component inherent to convergent orogenic systems.
Counter‐Electrojet Occurrence as Observed From C/NOFS Satellite and Ground‐Based Magnetometer Data Over the African and American Sectors
Authors: Habarulema John Bosco , Lefebvre Gabrielle , Moldwin Mark B. , Katamzi‐Joseph Zama T , Yizengaw Endawoke
Published: July 2019

An analysis of the counter‐electrojet occurrence (CEJ) during 2008–2014 is presented for the African and American sectors based on local daytime (0700–1700 LT) observations from the Communications and Navigation Outage Forecasting System (C/NOFS) vertical ion plasma drift (equivalent to vertical E×B at an altitude of about 400 km) and ground‐based magnetometers. Using quiet time (Kp≤ 3) data, differences and/or similarities between the two data sets with reference to local time and seasonal dependence are established. For the first time, it is shown that C/NOFS satellite data are consistent with magnetometer observations in identifying CEJ occurrences during all seasons. However, C/NOFS satellite data show higher CEJ occurrence rate for almost all seasons. With respect to local time, C/NOFS satellite observes more CEJ events than magnetometer observations by average of about 20% and 40% over the American and African sectors, respectively, despite both data sets showing similar trends in CEJ identification. Therefore, when a space weather event occurs, it is important to first establish the original variability nature and/or magnitude of the eastward electric field in equatorial regions before attributing the resulting changes to solar wind‐magnetosphere and ionosphere coupling processes since CEJ events can be present even during quiet conditions.
Target preference of Type III-A CRISPR-Cas complexes at the transcription bubble
Authors: Liu Tina Y. , Liu Jun-Jie , Aditham Abhishek J. , Nogales Eva , Doudna Jennifer A.
Published: July 2019

Type III-A CRISPR-Cas systems are prokaryotic RNA-guided adaptive immune systems that use a protein-RNA complex, Csm, for transcription-dependent immunity against foreign DNA. Csm can cleave RNA and single-stranded DNA (ssDNA), but whether it targets one or both nucleic acids during transcription elongation is unknown. Here, we show that binding of a Thermus thermophilus (T. thermophilus) Csm (TthCsm) to a nascent transcript in a transcription elongation complex (TEC) promotes tethering but not direct contact of TthCsm with RNA polymerase (RNAP). Biochemical experiments show that both TthCsm and Staphylococcus epidermidis (S. epidermidis) Csm (SepCsm) cleave RNA transcripts, but not ssDNA, at the transcription bubble. Taken together, these results suggest that Type III systems primarily target transcripts, instead of unwound ssDNA in TECs, for immunity against double-stranded DNA (dsDNA) phages and plasmids. This reveals similarities between Csm and eukaryotic RNA interference, which also uses RNA-guided RNA targeting to silence actively transcribed genes.
Zero-field nuclear magnetic resonance of chemically exchanging systems
Authors: Barskiy Danila A. , Tayler Michael C. D. , Marco-Rius Irene , Kurhanewicz John , Vigneron Daniel B. , Cikrikci Sevil , Aydogdu Ayca , Reh Moritz , Pravdivtsev Andrey N. , Hövener Jan-Bernd , Blanchard John W. , Wu Teng , Budker Dmitry , Pines Alexander
Published: July 2019

Zero- to ultralow-field (ZULF) nuclear magnetic resonance (NMR) is an emerging tool for precision chemical analysis. In this work, we study dynamic processes and investigate the influence of chemical exchange on ZULF NMR J-spectra. We develop a computational approach that allows quantitative calculation of J-spectra in the presence of chemical exchange and apply it to study aqueous solutions of [15N]ammonium (15N$${\mathrm{H}}_4^ +$$

H

4

+

) as a model system. We show that pH-dependent chemical exchange substantially affects the J-spectra and, in some cases, can lead to degradation and complete disappearance of the spectral features. To demonstrate potential applications of ZULF NMR for chemistry and biomedicine, we show a ZULF NMR spectrum of [2-13C]pyruvic acid hyperpolarized via dissolution dynamic nuclear polarization (dDNP). We foresee applications of affordable and scalable ZULF NMR coupled with hyperpolarization to study chemical exchange phenomena in vivo and in situations where high-field NMR detection is not possible to implement.
Metformin induces lipogenic differentiation in myofibroblasts to reverse lung fibrosis
Authors: Kheirollahi Vahid , Wasnick Roxana M. , Biasin Valentina , Vazquez-Armendariz Ana Ivonne , Chu Xuran , Moiseenko Alena , Weiss Astrid , Wilhelm Jochen , Zhang Jin-San , Kwapiszewska Grazyna , Herold Susanne , Schermuly Ralph T. , Mari Bernard , Li Xiaokun , Seeger Werner , Günther Andreas , Bellusci Saverio , El Agha Elie
Published: July 2019

Idiopathic pulmonary fibrosis (IPF) is a fatal disease in which the intricate alveolar network of the lung is progressively replaced by fibrotic scars. Myofibroblasts are the effector cells that excessively deposit extracellular matrix proteins thus compromising lung structure and function. Emerging literature suggests a correlation between fibrosis and metabolic alterations in IPF. In this study, we show that the first-line antidiabetic drug metformin exerts potent antifibrotic effects in the lung by modulating metabolic pathways, inhibiting TGFβ1 action, suppressing collagen formation, activating PPARγ signaling and inducing lipogenic differentiation in lung fibroblasts derived from IPF patients. Using genetic lineage tracing in a murine model of lung fibrosis, we show that metformin alters the fate of myofibroblasts and accelerates fibrosis resolution by inducing myofibroblast-to-lipofibroblast transdifferentiation. Detailed pathway analysis revealed a two-arm mechanism by which metformin accelerates fibrosis resolution. Our data report an antifibrotic role for metformin in the lung, thus warranting further therapeutic evaluation.
Survival probability of stochastic processes beyond persistence exponents
Authors: Levernier N. , Dolgushev M. , Bénichou O. , Voituriez R. , Guérin T.
Published: July 2019

For many stochastic processes, the probability$$S(t)$$S(t)of not-having reached a target in unbounded space up to time$$t$$tfollows a slow algebraic decay at long times,$$S(t) \sim {S}_{0}/{t}^{\theta }$$S(t)~S0∕tθ. This is typically the case of symmetric compact (i.e. recurrent) random walks. While the persistence exponent$$\theta$$θhas been studied at length, the prefactor$${S}_{0}$$S0, which is quantitatively essential, remains poorly characterized, especially for non-Markovian processes. Here we derive explicit expressions for$${S}_{0}$$S0for a compact random walk in unbounded space by establishing an analytic relation with the mean first-passage time of the same random walk in a large confining volume. Our analytical results for$${S}_{0}$$S0are in good agreement with numerical simulations, even for strongly correlated processes such as Fractional Brownian Motion, and thus provide a refined understanding of the statistics of longest first-passage events in unbounded space.
Upper tract urothelial carcinoma has a luminal-papillary T-cell depleted contexture and activated FGFR3 signaling
Authors: Robinson Brian D. , Vlachostergios Panagiotis J. , Bhinder Bhavneet , Liu Weisi , Li Kailyn , Moss Tyler J. , Bareja Rohan , Park Kyung , Tavassoli Peyman , Cyrta Joanna , Tagawa Scott T. , Nanus David M. , Beltran Himisha , Molina Ana M. , Khani Francesca , Miguel Mosquera Juan , Xylinas Evanguelos , Shariat Shahrokh F. , Scherr Douglas S. , Rubin Mark A. , Lerner Seth P. , Matin Surena F. , Elemento Olivier , Faltas Bishoy M.
Published: July 2019

Upper tract urothelial carcinoma (UTUC) is characterized by a distinctly aggressive clinical phenotype. To define the biological features driving this phenotype, we performed an integrated analysis of whole-exome and RNA sequencing of UTUC. Here we report several key insights from our molecular dissection of this disease: 1) Most UTUCs are luminal-papillary; 2) UTUC has a T-cell depleted immune contexture; 3) High FGFR3 expression is enriched in UTUC and correlates with its T-cell depleted immune microenvironment; 4) Sporadic UTUC is characterized by a lower total mutational burden than urothelial carcinoma of the bladder. Our findings lay the foundation for a deeper understanding of UTUC biology and provide a rationale for the development of UTUC-specific treatment strategies.
Multi-region exome sequencing reveals genomic evolution from preneoplasia to lung adenocarcinoma
Authors: Hu Xin , Fujimoto Junya , Ying Lisha , Fukuoka Junya , Ashizawa Kazuto , Sun Wenyong , Reuben Alexandre , Chow Chi-Wan , McGranahan Nicholas , Chen Runzhe , Hu Jinlin , Godoy Myrna C. , Tabata Kazuhiro , Kuroda Kishio , Shi Lei , Li Jun , Behrens Carmen , Parra Edwin Roger , Little Latasha D. , Gumbs Curtis , Mao Xizeng , Song Xingzhi , Tippen Samantha , Thornton Rebecca L. , Kadara Humam , Scheet Paul , Roarty Emily , Ostrin Edwin Justin , Wang Xu , Carter Brett W. , Antonoff Mara B. , Zhang Jianhua , Vaporciyan Ara A. , Pass Harvey , Swisher Stephen G. , Heymach John V. , Lee J. Jack , Wistuba Ignacio I. , Hong Waun Ki , Futreal P. Andrew , Su Dan , Zhang Jianjun
Published: July 2019

There has been a dramatic increase in the detection of lung nodules, many of which are preneoplasia atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) or invasive adenocarcinoma (ADC). The molecular landscape and the evolutionary trajectory of lung preneoplasia have not been well defined. Here, we perform multi-region exome sequencing of 116 resected lung nodules including AAH (n = 22), AIS (n = 27), MIA (n = 54) and synchronous ADC (n = 13). Comparing AAH to AIS, MIA and ADC, we observe progressive genomic evolution at the single nucleotide level and demarcated evolution at the chromosomal level supporting the early lung carcinogenesis model from AAH to AIS, MIA and ADC. Subclonal analyses reveal a higher proportion of clonal mutations in AIS/MIA/ADC than AAH suggesting neoplastic transformation of lung preneoplasia is predominantly associated with a selective sweep of unfit subclones. Analysis of multifocal pulmonary nodules from the same patients reveal evidence of convergent evolution.
Relaxin gene delivery mitigates liver metastasis and synergizes with check point therapy
Authors: Hu Mengying , Wang Ying , Xu Ligeng , An Sai , Tang Yu , Zhou Xuefei , Li Jingjing , Liu Rihe , Huang Leaf
Published: July 2019

Activated hepatic stellate cell (aHSC)-mediated liver fibrosis is essential to the development of liver metastasis. Here, we discover intra-hepatic scale-up of relaxin (RLN, an anti-fibrotic peptide) in response to fibrosis along with the upregulation of its primary receptor (RXFP1) on aHSCs. The elevated expression of RLN serves as a natural regulator to deactivate aHSCs and resolve liver fibrosis. Therefore, we hypothesize this endogenous liver fibrosis repair mechanism can be leveraged for liver metastasis treatment via enforced RLN expression. To validate the therapeutic potential, we utilize aminoethyl anisamide-conjugated lipid-calcium-phosphate nanoparticles to deliver plasmid DNA encoding RLN. The nanoparticles preferentially target metastatic tumor cells and aHSCs within the metastatic lesion and convert them as an in situ RLN depot. Expressed RLN reverses the stromal microenvironment, which makes it unfavorable for established liver metastasis to grow. In colorectal, pancreatic, and breast cancer liver metastasis models, we confirm the RLN gene therapy results in significant inhibition of metastatic progression and prolongs survival. In addition, enforced RLN expression reactivates intra-metastasis immune milieu. The combination of the RLN gene therapy with PD-L1 blockade immunotherapy further produces a synergistic anti-metastatic efficacy. Collectively, the targeted RLN gene therapy represents a highly efficient, safe, and versatile anti-metastatic modality, and is promising for clinical translation.
Uncovering the signaling landscape controlling breast cancer cell migration identifies novel metastasis driver genes
Authors: Koedoot Esmee , Fokkelman Michiel , Rogkoti Vasiliki-Maria , Smid Marcel , van de Sandt Iris , de Bont Hans , Pont Chantal , Klip Janna E. , Wink Steven , Timmermans Mieke A. , Wiemer Erik A. C. , Stoilov Peter , Foekens John A. , Le Dévédec Sylvia E. , Martens John W. M. , van de Water Bob
Published: July 2019

Ttriple-negative breast cancer (TNBC) is an aggressive and highly metastatic breast cancer subtype. Enhanced TNBC cell motility is a prerequisite of TNBC cell dissemination. Here, we apply an imaging-based RNAi phenotypic cell migration screen using two highly motile TNBC cell lines (Hs578T and MDA-MB-231) to provide a repository of signaling determinants that functionally drive TNBC cell motility. We have screened ~4,200 target genes individually and discovered 133 and 113 migratory modulators of Hs578T and MDA-MB-231, respectively, which are linked to signaling networks predictive for breast cancer progression. The splicing factors PRPF4B and BUD31 and the transcription factor BPTF are essential for cancer cell migration, amplified in human primary breast tumors and associated with metastasis-free survival. Depletion of PRPF4B, BUD31 and BPTF causes primarily down regulation of genes involved in focal adhesion and ECM-interaction pathways. PRPF4B is essential for TNBC metastasis formation in vivo, making PRPF4B a candidate for further drug development.
Divergent changes in the elevational gradient of vegetation activities over the last 30 years
Authors: Gao Mengdi , Piao Shilong , Chen Anping , Yang Hui , Liu Qiang , Fu Yongshuo H. , Janssens Ivan A.
Published: July 2019

The reported progressive change of vegetation activity along elevational gradients has important aesthetic and conservation values. With climate change, cooler locations are suggested to warm faster than warmer ones, raising concerns of a more homogenized landscape along the elevation. Here, we use global satellite data to investigate the spatio-temporal dynamics of the elevational gradient (EG) in vegetation greenness (NDVImax3), spring (SOS) and autumn phenology (EOS) during 1982–2015. Although we find clear geographical patterns of the EG in NDVImax3 and SOS, there are no prevalent trends of vegetation homogenization or phenology synchronization along elevational gradients. Possible mechanisms, including spatially heterogeneous temperature lapse rate changes, different vegetation sensitivities to climate change, and human disturbances, may play diverse roles across different regions. Our finding of mixed EG trends and no general rules controlling EG dynamics poses challenges for mitigating possible adverse impacts of climate change on mountainous biological diversity and ecosystem services.
Enhancement of laccase activity by pre-incubation with organic solvents
Authors: Wu Meng-Hsuan , Lin Meng-Chun , Lee Cheng-Chung , Yu Su-May , Wang Andrew H.-J. , Ho Tuan-Hua David
Published: July 2019

Laccases that are tolerant to organic solvents are powerful bio-catalysts with broad applications in biotechnology. Most of these uses must be accomplished at high concentration of organic solvents, during which proteins undergo unfolding, thereby losing enzyme activity. Here we show that organic-solvent pre-incubation provides effective and reversible 1.5- to 4.0-fold enhancement of enzyme activity of fungal laccases. Several organic solvents, including acetone, methanol, ethanol, DMSO, and DMF had an enhancement effect among all laccases studied. The enhancement was not substrate-specific and could be observed by using both phenolic and non-phenolic substrates. Laccase preincubated with organic solvents was sensitive to high temperature but remained stable at 25 °C, for an advantage for long-term storage. The acetone-pre-incubated 3-D structure of DLac, a high-efficiency fungal laccase, was determined and confirmed that the DLac protein structure remains intact and stable at a high concentration of organic solvent. Moreover, the turnover rates of fungal laccases were improved after organic-solvent pre-incubation, with DLac showing the highest enhancement among the fungal laccases examined. Our investigation sheds light on improving fungal laccase usage under extreme conditions and extends opportunities for bioremediation, decolorization, and organic synthesis.
Cathepsin Z as a novel potential biomarker for osteoporosis
Authors: Dera Ayed A. , Ranganath Lakshminarayan , Barraclough Roger , Vinjamuri Sobhan , Hamill Sandra , Barraclough Dong L.
Published: July 2019

Osteoporosis, one of the most prevalent chronic ageing-related bone diseases, often goes undetected until the first fragility fracture occurs, causing patient suffering and cost to health/social care services. Osteoporosis arises from imbalanced activity of osteoclasts and osteoblasts. Since these cell lineages produce the protease, cathepsin Z, the aim of this study was to investigate whether altered cathepsin Z mRNA levels are associated with osteoporosis in clinical samples. Cathepsin Z mRNA in human peripheral blood mononuclear cells was significantly differentially-expressed among non-osteoporotic controls, osteopenia and osteoporosis patients (p < 0.0001) and in female osteoporosis patients over the age of 50 years (P = 0.0016). Cathepsin Z mRNA level strongly correlated with low bone mineral density (BMD) (g/cm2), lumbar spine L2-L4 and femoral neck (T-scores) (P = 0.0149, 0.0002 and 0.0139, respectively). Importantly, cathepsin Z mRNA was significantly associated with fragility fracture in osteoporosis patients (P = 0.0018). The levels of cathepsin Z mRNA were not significantly higher in patients with chronic inflammatory disorders in these two groups compared to those without (P = 0.774 and 0.666, respectively). ROC analysis showed that cathepsin Z mRNA has strong diagnostic value for osteoporosis and osteoporotic fracture. The results show for the first time that cathepsin Z could be a future diagnostic biomarker for osteoporosis including female osteoporosis patients over the age of 50 years.
Antibiotic drug-resistance as a complex system driven by socio-economic growth and antibiotic misuse
Authors: Malik Bhawna , Bhattacharyya Samit
Published: July 2019

Overwhelming antibiotic use poses a serious challenge today to the public-health policymakers worldwide. Many empirical studies pointed out this ever-increasing antibiotic consumption as primary driver of the community-acquired antibiotic drug-resistance, especially in the middle- and lower-income countries. The association is well documented across spatio-temporal gradients in many parts of the world, but there is rarely any study that emphasizes the mechanism of the association, which is important for combating drug-resistance. Formulating a mathematical model of emergence and transmission of drug-resistance, we in this paper, present how amalgamating three components: socio-economic growth, population ecology of infectious disease, and antibiotic misuse can instinctively incite proliferation of resistance in the society. We show that combined impact of economy, infections, and self-medication yield synergistic interactions through feedbacks on each other, presenting the emergence of drug-resistance as a self-reinforcing cycle in the population. Analysis of our model not only determines the threshold of antibiotic use beyond which the emergence of resistance may occur, but also characterizes how fast it develops depending on economic growth, and lack of education and awareness of the population. Our model illustrates that proper and timely government aid in population health can break the self-reinforcing process and reduce the burden of drug-resistance in the community.
Evolutionary dynamics of organised crime and terrorist networks
Authors: Martinez-Vaquero Luis A. , Dolci Valerio , Trianni Vito
Published: July 2019

Crime is pervasive into modern societies, although with different levels of diffusion across regions. Its dynamics are dependent on various socio-economic factors that make the overall picture particularly complex. While several theories have been proposed to account for the establishment of criminal behaviour, from a modelling perspective organised crime and terrorist networks received much less attention. In particular, the dynamics of recruitment into such organisations deserve specific considerations, as recruitment is the mechanism that makes crime and terror proliferate. We propose a framework able to model such processes in both organised crime and terrorist networks from an evolutionary game theoretical perspective. By means of a stylised model, we are able to study a variety of different circumstances and factors influencing the growth or decline of criminal organisations and terrorist networks, and observe the convoluted interplay between agents that decide to get associated to illicit groups, criminals that prefer to act on their own, and the rest of the civil society.
Pregnancy outcomes of women with previous caesarean sections: Secondary analysis of World Health Organization Multicountry Survey on Maternal and Newborn Health
Authors: Kietpeerakool Chumnan , Lumbiganon Pisake , Laopaiboon Malinee , Rattanakanokchai Siwanon , Vogel Joshua P , Gülmezoglu A Metin
Published: July 2019

Secondary analysis of World Health Organization Multicountry Survey on Maternal and Newborn Health (WHOMCS) was undertaken among 173,124 multiparous women to assess the association between previous caesarean sections (CS) and pregnancy outcomes. Maternal outcomes included maternal near miss (MNM), maternal death (MD), severe maternal outcomes (SMO), abnormal placentation, and uterine rupture. Neonatal outcomes were stillbirth, early neonatal death, perinatal death, neonatal near miss (NNM), neonatal intensive care unit (NICU) admission, and preterm birth. Previous CS was associated with increased risks of uterine rupture (adjusted Odds Ratio (aOR); 7.74; 95% confidence interval (CI) 5.48, 10.92); morbidly adherent placenta (aOR 2.60; 95% CI 1.98, 3.40), MNM (aOR 1.91; 95% CI 1.59, 2.28), SMO (aOR 1.80; 95% CI 1.52, 2.13), placenta previa (aOR 1.76; 95% CI 1.49, 2.07). For neonatal outcomes, previous CS was associated with increased risks of NICU admission (aOR 1.31; 95% CI 1.23, 1.39), neonatal near miss (aOR 1.19; 95% CI 1.12, 1.26), preterm birth (aOR 1.07; 95% CI 1.01, 1.14), and decreased risk of macerated stillbirth (aOR 0.80; 95% CI 0.67, 0.95). Previous CS was associated with serious morbidity in future pregnancies. However, these findings should be cautiously interpreted due to lacking data on indications of previous CS.
Glomerular expression pattern of long non-coding RNAs in the type 2 diabetes mellitus BTBR mouse model
Authors: Reichelt-Wurm Simone , Wirtz Tobias , Chittka Dominik , Lindenmeyer Maja , Reichelt Robert M. , Beck Sebastian , Politis Panagiotis , Charonis Aristidis , Kretz Markus , Huber Tobias B. , Liu Shuya , Banas Bernhard , Banas Miriam C.
Published: July 2019

The prevalence of type 2 diabetes mellitus (T2DM) and by association diabetic nephropathy (DN) will continuously increase in the next decades. Nevertheless, the underlying molecular mechanisms are largely unknown and studies on the role of new actors like long non-coding RNAs (lncRNAs) barely exist. In the present study, the inherently insulin-resistant mouse strain “black and tan, brachyuric” (BTBR) served as T2DM model. While wild-type mice do not exhibit pathological changes, leptin-deficient diabetic animals develop a severe T2DM accompanied by a DN, which closely resembles the human phenotype. We analyzed the glomerular expression of lncRNAs from wild-type and diabetic BTBR mice (four, eight, 16, and 24 weeks) applying the “GeneChip Mouse Whole Transcriptome 1.0 ST” array. This microarray covered more lncRNA gene loci than any other array before. Over the observed time, our data revealed differential expression patterns of 1746 lncRNAs, which markedly differed from mRNAs. We identified protein-coding and non-coding genes, that were not only co-located but also co-expressed, indicating a potentially cis-acting function of these lncRNAs. In vitro-experiments strongly suggested a cell-specific expression of these lncRNA-mRNA-pairs. Additionally, protein-coding genes, being associated with significantly regulated lncRNAs, were enriched in various biological processes and pathways, that were strongly linked to diabetes.
Dissecting the role of the gut microbiota and diet on visceral fat mass accumulation
Authors: Le Roy Caroline I. , Bowyer Ruth C. E. , Castillo-Fernandez Juan E. , Pallister Tess , Menni Cristina , Steves Claire J. , Berry Sarah E. , Spector Tim D. , Bell Jordana T.
Published: July 2019

Both gut microbiota and diet have been shown to impact visceral fat mass (VFM), a major risk factor for cardiometabolic disease, but their relative contribution has not been well characterised. We aimed to estimate and separate the effect of gut microbiota composition from that of nutrient intake on VFM in 1760 older female twins. Through pairwise association analyses, we identified 93 operational taxonomic units (OTUs) and 10 nutrients independently linked to VFM (FDR < 5%). Conditional analyses revealed that the majority (87%) of the 93 VFM-associated OTUs remained significantly associated with VFM irrespective of nutrient intake correction. In contrast, we observed that the effect of fibre, magnesium, biotin and vitamin E on VFM was partially mediated by OTUs. Moreover, we estimated that OTUs were more accurate predictors of VFM than nutrients and accounted for a larger percentage of its variance. Our results suggest that while the role of certain nutrients on VFM appears to depend on gut microbiota composition, specific gut microbes may affect host adiposity regardless of dietary intake. The findings imply that the gut microbiota may have a greater contribution towards shaping host VFM than diet alone. Thus, microbial-based therapy should be prioritised for VFM reduction in overweight and obese subjects.
Engineering multi-layered tissue constructs using acoustic levitation
Authors: Tait Angela , Glynne-Jones Peter , Hill Alison R. , Smart David E. , Blume Cornelia , Hammarstrom Bjorn , Fisher Adam L. , Grossel Martin C. , Swindle Emily J. , Hill Martyn , Davies Donna E.
Published: July 2019

Engineering tissue structures that mimic those found in vivo remains a challenge for modern biology. We demonstrate a new technique for engineering composite structures of cells comprising layers of heterogeneous cell types. An acoustofluidic bioreactor is used to assemble epithelial cells into a sheet-like structure. On transferring these cell sheets to a confluent layer of fibroblasts, the epithelial cells cover the fibroblast surface by collective migration maintaining distinct epithelial and fibroblast cell layers. The collective behaviour of the epithelium is dependent on the formation of cell-cell junctions during levitation and contrasts with the behaviour of mono-dispersed epithelial cells where cell-matrix interactions dominate and hinder formation of discrete cell layers. The multilayered tissue model is shown to form a polarised epithelial barrier and respond to apical challenge. The method is useful for engineering a wide range of layered tissue types and mechanistic studies on collective cell migration.
Human adenovirus species C recombinant virus continuously circulated in China
Authors: Yang Jianfang , Mao Naiying , Zhang Chuangye , Ren Binzhi , Li Hong , Li Na , Chen Jing , Zhang Ruifu , Li Hong , Zhu Zhen , Xu Wenbo
Published: July 2019

To date, at least three lineages (Lineage 1–3) that are related to recombinant human adenovirus species C (HAdV-C) have been identified in China. Among them, Lineage 1 includes two Chinese strains, strain KR699642-CHN-20093 (CBJ11) and strain MF315029-CHN-2013 (BJ09), which were collected in Beijing in 2009 and 2013, respectively. Herein, we performed genomic and bioinformatics analysis of two HAdV-C strains (strain SX-2000-140 and strain SX-2004-327) that were isolated from the feces of two healthy children in Shanxi province of China in 2000 and 2004, respectively. Results revealed that the genomes of both Shanxi strains had the highest homology to two Chinese HAdV-C strains belonging to Lineage 1 and harbored the genetic elements of these two strains, thereby presuming that Lineage1 has been circulated in mainland of China for decades. In addition, though the viruses in Lineage 1 showed slightly different recombinant patterns resulting from the recombinant events among the five types of HAdV-C, all the Lineage 1 viruses shared the highest sequence similarities with the HAdV-2 prototype strain (NC_001405-USA-1953) across the genome, especially in the major capsid genes including hexon, and fiber. These results indicated that Lineage 1 viruses that were associated with recombinants shared a common ancestor that is closely related to the HAdV-2 virus. Our current findings confirmed that frequent recombination among the different HAdV-C types might be an important driving force for the molecular evolution of HAdV-C. Therefore, there is a strong need for further comprehensive and systematic monitoring, detection, and research on HAdV-C.
Skeletal stability after maxillary step osteotomy compared with original Le Fort I osteotomy during one-year of follow-up
Authors: Kurohara Kazuto , Tomomatsu Nobuyoshi , Nakakuki Koichi , Arai Naoya , Yoda Tetsuya
Published: July 2019

The purpose of the current study was to compare the 1-year stability of skeletal after original Le Fort I osteotomy and maxillary step osteotomy. Fifty-two patients with prognathism underwent sagittal split ramus osteotomy with either original Le Fort I osteotomy or maxillary step osteotomy (26 patients each). Twelve cephalometric parameters were measured to evaluate postsurgical stability (lesser change was considered as enhanced stability) at 1 month (T1), 6 months (T2), and 1 year (T3) postoperatively. Only 3 parameters—vertical and horizontal distance of menton and vertical distance of point B—showed minimal but significant differences between the two groups. Lesser degrees of changes were observed after maxillary step osteotomy than after original Le Fort I osteotomy, and the differences were significant during the period between T1 and T2, but not from T1 to T3. Differences between the two groups were less in asymmetry cases required correction of the occlusal plane. In conclusion, differences between original Le Fort I osteotomy and maxillary step osteotomy were observed at the frontal points of the mandible; however, they were not clinically significant. It may be suggested that there is no significant difference in skeletal stability at 1 year after the two procedures.
TRPC3-Nox2 axis mediates nutritional deficiency-induced cardiomyocyte atrophy
Authors: Sudi Suhaini Binti , Tanaka Tomohiro , Oda Sayaka , Nishiyama Kazuhiro , Nishimura Akiyuki , Sunggip Caroline , Mangmool Supachoke , Numaga-Tomita Takuro , Nishida Motohiro
Published: July 2019

Myocardial atrophy, characterized by the decreases in size and contractility of cardiomyocytes, is caused by severe malnutrition and/or mechanical unloading. Extracellular adenosine 5′-triphosphate (ATP), known as a danger signal, is recognized to negatively regulate cell volume. However, it is obscure whether extracellular ATP contributes to cardiomyocyte atrophy. Here, we report that ATP induces atrophy of neonatal rat cardiomyocytes (NRCMs) without cell death through P2Y2 receptors. ATP led to overproduction of reactive oxygen species (ROS) through increased amount of NADPH oxidase (Nox) 2 proteins, due to increased physical interaction between Nox2 and canonical transient receptor potential 3 (TRPC3). This ATP-mediated formation of TRPC3-Nox2 complex was also pathophysiologically involved in nutritional deficiency-induced NRCM atrophy. Strikingly, knockdown of either TRPC3 or Nox2 suppressed nutritional deficiency-induced ATP release, as well as ROS production and NRCM atrophy. Taken together, we propose that TRPC3-Nox2 axis, activated by extracellular ATP, is the key component that mediates nutritional deficiency-induced cardiomyocyte atrophy.
Effect of neurokinin-1-receptor blockage on fracture healing in rats
Authors: Hofman Martijn , Rabenschlag Frederik , Andruszkow Hagen , Andruszkow Julia , Möckel Diana , Lammers Twan , Kolejewska Aneta , Kobbe Philipp , Greven Johannes , Teuben Michel , Poeze Martijn , Hildebrand Frank
Published: July 2019

Neurologic injury and selective blockage of sensory nerve endings is associated with impaired fracture healing, however, the role of specific neurotransmitters has not been sufficiently investigated. Our aim was to investigate the impact of specific Substance P-receptor blockage on fracture healing, since the neuropeptide Substance P has both neurogenic and osteogenic activity. After intramedullary stabilization, an isolated femur fracture was induced in 72 Sprague-Dawley rats. In the NK1-R group, the neurokinin-1-tachykinin receptor for substance P was blocked by a specific antagonist (SR140333) for the first two weeks after fracture induction. The control group only received vehicle. Gene-expression, histology, micro-computed tomography, and biomechanical tests were performed. NK1-receptor blocking suppressed osteocalcin expression at one week, collagen 1A2 expression at one and two weeks and collagen 2A1 expression at 2 weeks after fracture induction. Biomechanical testing revealed a significant reduction in maximal load to failure in the NK1-R group at 6 weeks (69.78 vs. 155.45 N, p = 0.029) and at 3 months (72.50 vs.176.33 N, p = 0.01) of fracture healing. Blocking the NK1-receptor suppresses gene expression in and reduces biomechanical strength of healing bone. Therefore, we assume a potential therapeutic relevance of Substance P in cases of disturbed fracture healing.
Radiogenomics-based cancer prognosis in colorectal cancer
Authors: Badic Bogdan , Hatt Mathieu , Durand Stephanie , Jossic-Corcos Catherine Le , Simon Brigitte , Visvikis Dimitris , Corcos Laurent
Published: July 2019

Radiogenomics aims at investigating the relationship between imaging radiomic features and gene expression alterations. This study addressed the potential prognostic complementary value of contrast enhanced computed tomography (CE-CT) radiomic features and gene expression data in primary colorectal cancers (CRC). Sixty-four patients underwent CT scans and radiomic features were extracted from the delineated tumor volume. Gene expression analysis of a small set of genes, previously identified as relevant for CRC, was conducted on surgical samples from the same tumors. The relationships between radiomic and gene expression data was assessed using the Kruskal–Wallis test. Multiple testing was not performed, as this was a pilot study. Cox regression was used to identify variables related to overall survival (OS) and progression free survival (PFS). ABCC2 gene expression was correlated with N (p = 0.016) and M stages (p = 0.022). Expression changes of ABCC2, CD166, CDKNV1 and INHBB genes exhibited significant correlations with some radiomic features. OS was associated with Ratio 3D Surface/volume (p = 0.022) and ALDH1A1 expression (p = 0.042), whereas clinical stage (p = 0.004), ABCC2 expression (p = 0.035), and EntropyGLCM_E (p = 0.0031), were prognostic factors for PFS. Combining CE-CT radiomics with gene expression analysis and histopathological examination of primary CRC could provide higher prognostic stratification power, leading to improved patient management.
Optical and polarization properties of nonpolar InGaN-based light-emitting diodes grown on micro-rod templates
Authors: Bai J. , Jiu L. , Poyiatzis N. , Fletcher P. , Gong Y. , Wang T.
Published: July 2019

We have demonstrated non-polar a-plane InGaN multiple-quantum-well (MQW) light-emitting diodes (LEDs) on sapphire, achieved by overgrowing on a micro-rod template with substantially improved crystal quality. Photoluminescence measurements show one main emission peak at 418 nm along with another weak peak at 448 nm. Wavelength mapping measurements carried out by using a high spatial-resolution confocal PL system indicate that the two emissions origin from different areas associated with the underlying micro-rod patterns. Electroluminescence measurements exhibit a negligible blue-shift of 1.6 nm in the peak wavelength of the main emission when the driving current increases from 10 to 100 mA, indicating that the quantum confined Stark effect is effectively suppressed in in the nonpolar LED. A polarization ratio of 0.49 is obtained for the low-energy emission (~448 nm), while the main emission (~418 nm) shows a polarization ratio of 0.34. Furthermore, the polarization ratios are independent of injection current, while the energy separation between m-polarized and c-polarized lights increases with the injection current for both emissions.