bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐Resolution Gravity Field Models from GRAIL Data and Implications for Models of the Density Structure of the Moon's Crust
Authors: Goossens S. , Sabaka T. J. , Wieczorek M. A. , Neumann G. A. , Mazarico E. , Lemoine F. G. , Nicholas J. B. , Smith D. E. , Zuber M. T.
Published: November 2019

We present our latest high‐resolution lunar gravity field model of degree and order 1200 in spherical harmonics using Gravity Recovery and Interior Laboratory (GRAIL) data. In addition to a model with the standard spectral Kaula regularization constraint, we determine models by applying a constraint based on topography called rank‐minus‐one (RM1). The new models using this RM1 constraint have high correlations with topography over the entire degree range by design. The RM1 models allow the determination of apparent crustal densities at all spatial scales (called effective density) covered by the model, whereas the Kaula‐constrained model can only be used globally up to spherical harmonic degree 700. We find that the effective density spectrum has a smaller slope for the high degrees when compared to the medium degrees. We interpret this as indicative of a global average surface density, as opposed to an ever‐decreasing effective density as one approaches the surface. We use the RM1 models to derive maps of lateral and vertical density variations in the lunar crust. These models allow us to increase the resolution of this analysis compared to previous studies, by increasing the degree range over which to fit theoretical models of vertical density variations, and by decreasing the size of the spherical caps used in a localized analysis. Several regions on the Moon, such as South Pole‐Aitken and Mare Orientale, are distinct from their surroundings in terms of surface densities. The RM1 models are especially valuable in (localized) spectral studies of the structure of the lunar crust.
Links of Extracellular Enzyme Activities, Microbial Metabolism, and Community Composition in the River‐Impacted Coastal Waters
Authors: Shi Zhen , Xu Jie , Li Xiangfu , Li Ruihuan , Li Qian
Published: November 2019

Extracellular enzymatic activity (EEA), production, respiration, and composition of the bacterial community were determined along environmental gradients in the river‐impacted coastal waters in the South China Sea during summer in order to examine the links of EEA, metabolic activity, and composition of the bacterial community. The initial step of substrate utilization was coupled with metabolic activity of the bacterial community. The activity of leucine aminopeptidase was closely related to the level of phytoplankton biomass, suggesting that leucine‐containing compounds primarily resulted from phytoplankton, which was likely partly responsible for the close link between bacterioplankton and phytoplankton in marine environments. A shift from the dominance of leucine aminopeptidase in EEA in eutrophic environments to chitobiases in pristine waters was attributed to bacterial preference for leucine‐containing compounds and spatial variability in substrate supply. Spatial pattern of the enzymatic rates along an environmental gradient differed at the community and the cellular level. The enzymatic rates of the bacterial community decreased offshore, which were linked to substrate supply and the bacterial community composition. However, cell‐specific enzymatic rates were modulated by not only the bacterial community composition but also the carbon partition between anabolic and catabolic processes as environmental conditions changed, both of which eventually altered bacterial abundance. Functional redundancy of bacterial groups existed despite shifts in the bacterial community composition, suggesting that the bacterial community might maximize their function of hydrolyzing substrates across marine environments. Our findings improved the understanding of the connection of extracellular enzymatic activity, metabolic activity, and community composition of bacterioplankton.
Higher CO2 Concentrations and Lower Acidic Deposition Have Not Changed Drought Response in Tree Growth But Do Influence iWUE in Hardwood Trees in the Midwestern United States
Authors: Maxwell Justin T. , Harley Grant L. , Mandra Tessa E. , Yi Koong , Kannenberg Steven A. , Au Tsun Fung , Robeson Scott M. , Pederson Neil , Sauer Peter E. , Novick Kimberly A.
Published: November 2019

Several important environmental influences of tree growth and carbon sequestration have changed over the past several decades in eastern North America, specifically, more frequent pluvial conditions, increased carbon dioxide (CO2) concentrations, and decreased acidic deposition. These factors could lead to changes in the relationship between tree growth and water availability, and perhaps even decouple the two, having large implications on how future climate change will impact forest productivity and carbon sequestration. Here, we examine the concurrent influence of the climatic water balance (precipitation minus potential evapotranspiration), CO2 concentrations, and sulfate and nitrogen deposition on radial tree growth, carbon isotopes, and intrinsic water‐use efficiency (iWUE) for several hardwood tree species in the Midwestern United States. We found that when considering the simultaneous influence of these factors, the climatic water balance is the dominant influence on annual growth. Therefore, the recent pluvial period is the primary cause of the weakening relationship between radial growth and water availability. Even during pluvial periods, water availability is the primary control on growth, with increasing CO2 concentrations and decreased SO4 deposition being secondary factors. Importantly, the weakening in the climate‐growth relationship is species specific, with Acer species having stable relationships with the climatic water balance, Liriodendron tulipifera showing a strengthening relationship, and Quercus species and Populus grandidentata exhibiting weakening. Thus, interannual variations in soil moisture unevenly impact tree growth and carbon sequestration. Our findings suggest that, despite recent pluvial conditions, increasing CO2 concentrations and decreasing acidic deposition have not buffered the impact of water availability on tree growth and carbon sequestration.
From Submarine to Subaerial Out‐of‐Sequence Thrusting and Gravity‐Driven Extensional Faulting: Gran Sasso Massif, Central Apennines, Italy
Authors: Lucca Alessio , Storti Fabrizio , Balsamo Fabrizio , Clemenzi Luca , Fondriest Michele , Burgess Ray , Di Toro Giulio
Published: November 2019

Thrust wedge evolution is typically characterized by out‐of‐sequence thrusting, which can occur in both submarine and subaerial conditions to maintain the balance between gravitational and tectonic forces. The Gran Sasso Massif, in Central Italy, is a high topography region where the kinematics and environmental conditions of deformation of some fault zones are still controversial, and this bears important implications for the Central Apennines orogenic wedge evolution. To obtain further constraints on fault activity in the Gran Sasso Massif, we studied the Monte Camicia and Vado di Ferruccio thrusts using structural, petrographical, and geochemical analyses. Such dataset allowed us to constrain the structural‐diagenetic evolution of the studied faults, which has first‐order implications in the characterization of their paleo‐hydraulic properties. Our results indicate that in the Vado di Ferruccio out‐of‐sequence thrust, pressure solution‐mediated mass transfer promoted low‐permeability conditions in the fault core that led to a semiclosed fluid circulation, pore fluid overpressuring, and dolomite crystallization in submarine conditions. In contrast, the Monte Camicia out‐of‐sequence thrust was characterized by dominant cataclasis in subaerial conditions, which facilitated meteoric fluid infiltration. By considering both fault zones as belonging to the same thrust system at crustal scale, we interpret these differences as indicating the occurrence of multiple pulses of thrusting during the exhumation of this sector of the Central Apennines, up to Quaternary times, when extensional faulting eventually dissected the thrust stack. This caused extensional reactivation of the Monte Camicia Thrust and related alteration in vadose zone conditions, leading to porosity enhancement, dolomite dissolution, and calcitization.
Global‐Scale Prediction of Flood Timing Using Atmospheric Reanalysis
Authors: Do Hong Xuan , Westra Seth , Leonard Michael , Gudmundsson Lukas
Published: November 2019

The annual timing of flood events is a useful indicator to study the interaction between atmospheric and catchment processes in generating floods. This paper presents an assessment of the seasonal timing of floods for 7,894 gauging locations across the globe over a common period from 1981 to 2010. The averaged ordinal date of annual maximum streamflow is then estimated for ungauged locations following a two‐stage prediction scheme. The first stage identifies regions that share a common climatic predictor of flood timing by analyzing the similarity of flood timing with seven climate variables. These variables represent precipitation timing and snowmelt dynamics and are derived from a global climate reanalysis data set. Homogeneous regions in terms of the dominant predictor are generalized in the second stage through a rule‐based classification. The classification partitions the world into five hydroclimate classes, where each class has flood timing predicted using the most relevant climate predictor. Using this relatively simple and interpretable model structure, flood timing could be predicted with a global mean absolute error of approximately 31 days while maintaining consistency across large regions. Potential applications of the developed map include better understanding of climatic drivers of flooding and benchmarking the performance of global hydrological models in simulating the processes relevant to flooding.
Urbanization in Arid Central Arizona Watersheds Results in Decreased Stream Flashiness
Authors: McPhillips L. E. , Earl S. R. , Hale R. L. , Grimm N. B.
Published: November 2019

There is broad consensus that urbanization results in dramatic changes in stream hydrology, such as higher peak flows and greater flashiness. However, this has not been definitively tested for aridlands, which are characterized by these very same hydrograph properties. We analyzed streamflow records from 19 watersheds of central Arizona, USA, to determine how hydrograph characteristics varied with urban development. Using linear mixed effects models, which factored in imperviousness along with other watershed characteristics, we evaluated influences on streamflow regime metrics calculated from daily and subdaily flow data. We found that flashiness, coefficient of variation, zero‐flow days, and hydrograph rise and fall rates decreased with extent of imperviousness—the opposite pattern to that observed in previous studies primarily in humid regions. Engineered retention basins are one explanation for this observation though novel urban sources of dry weather flows are likely also playing a role. We also found strong relationships between these hydrologic metrics and mean area‐weighted discharge, watershed area, and annual precipitation. Like in humid systems, we did observe more high flow events in the urban desert streams compared to nonurban desert streams. However, this was only at the lower flood threshold; there was no increase in larger floods with urban development. Overall, the urban stream syndrome manifests differently in this arid system: Urbanization increases water retention and leads to less variable flows in stream ecosystems.
Post-neoadjuvant cellular dissociation grading based on tumour budding and cell nest size is associated with therapy response and survival in oesophageal squamous cell carcinoma
Authors: Jesinghaus Moritz , Boxberg Melanie , Wilhelm Dirk , Münch Stefan , Dapper Hendrik , Quante Michael , Schlag Christoph , Lange Sebastian , Budczies Jan , Konukiewitz Björn , Mollenhauer Martin , Schlitter Anna Melissa , Becker Karl Friedrich , Feith Marcus , Friess Helmut , Steiger Katja , Combs Stephanie E. , Weichert Wilko
Published: November 2019

Background

Cellular Dissociation Grade (CDG) composed of tumour budding and cell nest size has been shown to independently predict prognosis in pre-therapeutic biopsies and primary resections of oesophageal squamous cell carcinoma (ESCC). Here, we aimed to evaluate the prognostic impact of CDG in ESCC after neoadjuvant therapy.

Methods

We evaluated cell nest size and tumour budding activity in 122 post-neoadjuvant ESCC resections, correlated the results with tumour regression groups and patient survival and compared the results with data from primary resected cases as well as pre-therapeutic biopsies.

Results

CDG remained stable when results from pre-therapeutic biopsies and post-therapeutic resections from the same patient were compared. CDG was associated with therapy response and a strong predictor of overall, disease-specific (DSS) and disease-free (DFS) survival in univariate analysis and—besides metastasis—remained the only significant survival predictor for DSS and DFS in multivariate analysis. Multivariate DFS hazard ratios reached 3.3 for CDG-G2 and 4.9 for CDG-G3 neoplasms compared with CDG-G1 carcinomas (p = 0.016).

Conclusions

CDG is the only morphology-based grading algorithm published to date, which in concert with regression grading, is able to contribute relevant prognostic information in the post-neoadjuvant setting of ESCC.
Pwp1 regulates telomere length by stabilizing shelterin complex and maintaining histone H4K20 trimethylation
Authors: Yu Yangyang , Jia Wenwen , Lyu Yao , Su Dingwen , Bai Mingliang , Shen Junwei , Qiao Jing , Han Tong , Liu Wenqiang , Chen Jiayu , Chen Wen , Ye Dan , Guo Xudong , Zhu Songcheng , Xi Jiajie , Zhu Ruixin , Wan Xiaoping , Gao Shaorong , Zhu Jiyue , Kang Jiuhong
Published: November 2019

Telomere maintenance is critical for chromosome stability. Here we report that periodic tryptophan protein 1 (PWP1) is involved in regulating telomere length homeostasis. Pwp1 appears to be essential for mouse development and embryonic stem cell (ESC) survival, as homozygous Pwp1-knockout mice and ESCs have never been obtained. Heterozygous Pwp1-knockout mice had shorter telomeres and decreased reproductive capacity. Pwp1 depletion induced rapid telomere shortening accompanied by reduced shelterin complex and increased DNA damage in telomeric regions. Mechanistically, PWP1 bound and stabilized the shelterin complex via its WD40 domains and regulated the overall level of H4K20me3. The rescue of telomere length in Pwp1-deficient cells by PWP1 overexpression depended on SUV4-20H2 co-expression and increased H4K20me3. Therefore, our study revealed a novel protein involved in telomere homeostasis in both mouse and human cells. This knowledge will improve our understanding of how chromatin structure and histone modifications are involved in maintaining telomere integrity.
Solar and wind energy enhances drought resilience and groundwater sustainability
Authors: He Xiaogang , Feng Kairui , Li Xiaoyuan , Craft Amy B. , Wada Yoshihide , Burek Peter , Wood Eric F. , Sheffield Justin
Published: November 2019

Water scarcity brings tremendous challenges to achieving sustainable development of water resources, food, and energy security, as these sectors are often in competition, especially during drought. Overcoming these challenges requires balancing trade-offs between sectors and improving resilience to drought impacts. An under-appreciated factor in managing the water-food-energy (WFE) nexus is the increased value of solar and wind energy (SWE). Here we develop a trade-off frontier framework to quantify the water sustainability value of SWE through a case study in California. We identify development pathways that optimize the economic value of water in competition for energy and food production while ensuring sustainable use of groundwater. Our results indicate that in the long term, SWE penetration creates beneficial feedback for the WFE nexus: SWE enhances drought resilience and benefits groundwater sustainability, and in turn, maintaining groundwater at a sustainable level increases the added value of SWE to energy and food production.
Evolving perspectives on the sources of the frequency-following response
Authors: Coffey Emily B. J. , Nicol Trent , White-Schwoch Travis , Chandrasekaran Bharath , Krizman Jennifer , Skoe Erika , Zatorre Robert J. , Kraus Nina
Published: November 2019

The auditory frequency-following response (FFR) is a non-invasive index of the fidelity of sound encoding in the brain, and is used to study the integrity, plasticity, and behavioral relevance of the neural encoding of sound. In this Perspective, we review recent evidence suggesting that, in humans, the FFR arises from multiple cortical and subcortical sources, not just subcortically as previously believed, and we illustrate how the FFR to complex sounds can enhance the wider field of auditory neuroscience. Far from being of use only to study basic auditory processes, the FFR is an uncommonly multifaceted response yielding a wealth of information, with much yet to be tapped.
EGFL9 promotes breast cancer metastasis by inducing cMET activation and metabolic reprogramming
Authors: Meng Fanyan , Wu Ling , Dong Lun , Mitchell Allison V. , James Block C. , Liu Jenney , Zhang Haijun , Lu Qing , Song Won-min , Zhang Bin , Chen Wei , Hu Jiani , Wang Jian , Yang Qifeng , Hüttemann Maik , Wu Guojun
Published: November 2019

The molecular mechanisms driving metastatic progression in triple-negative breast cancer (TNBC) patients are poorly understood. In this study, we demonstrate that epidermal growth factor-like 9 (EGFL9) is significantly upregulated in basal-like breast cancer cells and associated with metastatic progression in breast tumor samples. Functionally, EGFL9 is both necessary and sufficient to enhance cancer cell migration and invasion, as well as distant metastasis. Mechanistically, we demonstrate that EGFL9 binds cMET, activating cMET-mediated downstream signaling. EGFL9 and cMET co-localize at both the cell membrane and within the mitochondria. We further identify an interaction between EGFL9 and the cytochrome c oxidase (COX) assembly factor COA3. Consequently, EGFL9 regulates COX activity and modulates cell metabolism, promoting a Warburg-like metabolic phenotype. Finally, we show that combined pharmacological inhibition of cMET and glycolysis reverses EGFL9-driven stemness. Our results identify EGFL9 as a therapeutic target for combating metastatic progression in TNBC.
Reprioritization of biofilm metabolism is associated with nutrient adaptation and long-term survival of Haemophilus influenzae
Authors: Harrison Alistair , Hardison Rachael L. , Wallace Rachel M. , Fitch James , Heimlich Derek R. , Bryan Meghan O’ , Dubois Laura , John-Williams Lisa St. , Sebra Robert P. , White Peter , Moseley M. Arthur , Thompson J. Will , Justice Sheryl S. , Mason Kevin M.
Published: November 2019

Nontypeable Haemophilus influenzae (NTHI) is a human-restricted pathogen with an essential requirement for heme–iron acquisition. We previously demonstrated that microevolution of NTHI promotes stationary phase survival in response to transient heme–iron restriction. In this study, we examine the metabolic contributions to biofilm formation using this evolved NTHI strain, RM33. Quantitative analyses identified 29 proteins, 55 transcripts, and 31 metabolites that significantly changed within in vitro biofilms formed by RM33. The synthesis of all enzymes within the tryptophan and glycogen pathways was significantly increased in biofilms formed by RM33 compared with the parental strain. In addition, increases were observed in metabolite transport, adhesin production, and DNA metabolism. Furthermore, we observed pyruvate as a pivotal point in the metabolic pathways associated with changes in cAMP phosphodiesterase activity during biofilm formation. Taken together, changes in central metabolism combined with increased stores of nutrients may serve to counterbalance nutrient sequestration.
Multiple intertwined pairing states and temperature-sensitive gap anisotropy for superconductivity at a nematic quantum-critical point
Authors: Klein Avraham , Wu Yi-Ming , Chubukov Andrey V.
Published: November 2019

The proximity of many strongly correlated superconductors to density-wave or nematic order has led to an extensive search for fingerprints of pairing mediated by dynamical quantum-critical (QC) fluctuations of the corresponding order parameter. Here we study anisotropic s-wave superconductivity induced by anisotropic QC dynamical nematic fluctuations. We solve the non-linear gap equation for the pairing gap $$\Delta (\theta ,{\omega }_{m})$$

Δ

(

θ
,

ω

m

)

and show that its angular dependence strongly varies below $${T}_{{\rm{c}}}$$

T

c

. We show that this variation is a signature of QC pairing and comes about because there are multiple s-wave pairing instabilities with closely spaced transition temperatures $${T}_{{\rm{c}},n}$$

T

c
,
n

. Taken alone, each instability would produce a gap $$\Delta (\theta ,{\omega }_{m})$$

Δ

(

θ
,

ω

m

)

that changes sign $$8n$$

8
n

times along the Fermi surface. We show that the equilibrium gap $$\Delta (\theta ,{\omega }_{m})$$

Δ
(
θ
,

ω

m

)

is a superposition of multiple components that are nonlinearly induced below the actual $${T}_{{\rm{c}}}={T}_{{\rm{c}},0}$$

T

c

=

T

c
,
0

, and get resonantly enhanced at $$T={T}_{{\rm{c}},n}\ <\ {T}_{{\rm{c}}}$$

T
=

T

c
,
n

<

T

c

. This gives rise to strong temperature variation of the angular dependence of $$\Delta (\theta ,{\omega }_{m})$$

Δ

(

θ
,

ω

m

)

. This variation progressively disappears away from a QC point.
CD109 acts as a gatekeeper of the epithelial trait by suppressing epithelial to mesenchymal transition in squamous cell carcinoma cells in vitro
Authors: Zhou Shufeng , da Silva Sabrina Daniela , Siegel Peter M. , Philip Anie
Published: November 2019

There is increasing evidence that the expression of CD109, a GPI-anchored cell surface protein is dysregulated in squamous cell carcinoma (SCC). However, the functional role of CD109 in SCC progression is poorly understood. In current study, we demonstrate that CD109 is a critical regulator of epithelial phenotype in SSC cells. CD109 levels inversely correlate with TGF-β signaling, EMT, migration, and invasion in cultured SCC cells. CRISPR/Cas9-mediated knockout CD109 (CD109 KO) in SCC cells represses epithelial traits and promotes the mesenchymal phenotype, as evidenced by elevated expression of mesenchymal proteins and markers of epithelial to mesenchymal transition. Treatment with recombinant CD109 protein causes CD109 KO cells to regain their epithelial traits. CD109 loss results in pronounced alterations of gene expression as detected by microarray analysis and in dysregulation of 15 important signalling pathways as shown by KEGG pathway cluster analysis. Validation using 52 human oral SCC tumor samples show that CD109 levels inversely correlate with tumor grade and the activation state of one such pathway, the TGF-β signaling pathway. Taken together, our findings highlight a novel role for CD109 as a gatekeeper of the epithelial phenotype by regulating TGF-β pathway in SCC cells.
Comparison of Familial Clustering of Anogenital and Skin Cancers Between In Situ and Invasive Types
Authors: Zhang Luyao , Hemminki Otto , Zheng Guoqiao , Försti Asta , Sundquist Kristina , Sundquist Jan , Hemminki Kari
Published: November 2019

Literature on familial risk of carcinomasin situ(CISs) is limited because many cancer registries do not collect information on CIS. In Sweden CISs are collected, and we used these data to analyze familial relative risks (RRs) for concordant (CIS-CIS) types of anogenital (cervical, other female and male genital and anal) and skin squamous cell CIS; additionally RRs were assessed between CIS types and between CIS and invasive forms. RRs were calculated for the offspring generations when family members were diagnosed CIS. Case numbers for CIS ranged from 330 in anal to 177,285 in cervical CIS. Significant concordant CIS-CIS RRs were 2.74 for female genital, 1.77 for cervical and 2.29 for SCC skin CISs. The CIS forms associated also with each other, except for cervical and skin CIS types. RRs for concordant CIS-invasive cancer associations were lower than CIS-CIS associations. Cervical CIS associated with non-Hodgkin CIS which may suggest immune dysfunction as a contributing factors. The results for anogenital CIS types suggest that life style related human papilloma virus infections contributed to the observed familial associations. Lower risks for CIS-invasive cancer than CIS-CIS suggest that CIS and invasive cancers share only partially risk factors that underlie familial clustering.
Mapping quantitative trait loci for yield-related traits and predicting candidate genes for grain weight in maize
Authors: Zhao Yanming , Su Chengfu
Published: November 2019

Quantitative trait loci (QTLs) mapped in different genetic populations are of great significance for marker-assisted breeding. In this study, an F2:3 population were developed from the crossing of two maize inbred lines SG-5 and SG-7 and applied to QTL mapping for seven yield-related traits. The seven traits included 100-kernel weight, ear length, ear diameter, cob diameter, kernel row number, ear weight, and grain weight per plant. Based on an ultra-high density linkage map, a total of thirty-three QTLs were detected for the seven studied traits with composite interval mapping (CIM) method, and fifty-four QTLs were indentified with genome-wide composite interval mapping (GCIM) methods. For these QTLs, Fourteen were both detected by CIM and GCIM methods. Besides, eight of the thirty QTLs detected by CIM were identical to those previously mapped using a F2 population (generating from the same cross as the mapping population in this study), and fifteen were identical to the reported QTLs in other recent studies. For the fifty-four QTLs detected by GCIM, five of them were consistent with the QTLs mapped in the F2 population of SG-5 × SG-7, and twenty one had been reported in other recent studies. The stable QTLs associated with grain weight were located on maize chromosomes 2, 5, 7, and 9. In addition, differentially expressed genes (DEGs) between SG-5 and SG-7 were obtained from the transcriptomic profiling of grain at different developmental stages and overlaid onto the stable QTLs intervals to predict candidate genes for grain weight in maize. In the physical intervals of confirmed QTLs qKW-7, qEW-9, qEW-10, qGWP-6, qGWP-8, qGWP-10, qGWP-11 and qGWP-12, there were 213 DEGs in total. Finally, eight genes were predicted as candidate genes for grain size/weight. In summary, the stable QTLs would be reliable and the candidate genes predicted would be benefit for maker assisted breeding or cloning.
Effect of asthma control on general health-related quality of life in patients diagnosed with adult-onset asthma
Authors: Ilmarinen Pinja , Juboori Hind , Tuomisto Leena E. , Niemelä Onni , Sintonen Harri , Kankaanranta Hannu
Published: November 2019

Health-related quality of life (HRQoL) is a well-established aspect of health that can be measured by both disease-specific and general instruments. The effect of uncontrolled asthma on generic HRQoL has not been shown in patients with clinically confirmed adult-onset asthma and with asthma control defined according to the Global Initiative for Asthma, so the aim of this study was to determine this. In the 12-year follow-up cohort of the Seinäjoki Adult Asthma Study (n = 203), patients with uncontrolled and partially controlled asthma had lower generic HRQoL as determined by 15D compared to the controlled group. On 10 out of 15 dimensions of 15D, the mean scores were significantly lower in patients with uncontrolled asthma compared with those with controlled asthma. The affected dimensions were mobility, breathing, sleeping, usual activities, mental function, discomfort and symptoms, depression, distress, vitality and sexual activity. In the Tobit regression analysis, a poorer 15D score was associated with uncontrolled asthma, lower postbronchodilator FEV1, female sex, depression, treated dyspepsia and poorer 15D score at diagnosis. Our results show that uncontrolled asthma affects everyday life in several aspects, including previously unknown components such as sexual activity and vitality.
Extensive Expression Analysis of Htt Transcripts in Brain Regions from the zQ175 HD Mouse Model Using a QuantiGene Multiplex Assay
Authors: Papadopoulou Aikaterini S. , Gomez-Paredes Casandra , Mason Michael A. , Taxy Bridget A. , Howland David , Bates Gillian P.
Published: November 2019

Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by a CAG repeat expansion within exon 1 of the huntingtin (HTT) gene. HTT mRNA contains 67 exons and does not always splice between exon 1 and exon 2 leading to the production of a small polyadenylated HTTexon1 transcript, and the full-length HTT mRNA has three 3′UTR isoforms. We have developed a QuantiGene multiplex panel for the simultaneous detection of all of these mouse Htt transcripts directly from tissue lysates and demonstrate that this can replace the more work-intensive Taqman qPCR assays. We have applied this to the analysis of brain regions from the zQ175 HD mouse model and wild type littermates at two months of age. We show that the incomplete splicing of Htt occurs throughout the brain and confirm that this originates from the mutant and not endogenous Htt allele. Given that HTTexon1 encodes the highly pathogenic exon 1 HTT protein, it is essential that the levels of all Htt transcripts can be monitored when evaluating HTT lowering approaches. Our QuantiGene panel will allow the rapid comparative assessment of all Htt transcripts in cell lysates and mouse tissues without the need to first extract RNA.
Comparison of oral microbiome profiles in stimulated and unstimulated saliva, tongue, and mouth-rinsed water
Authors: Jo Ryutaro , Nishimoto Yuichiro , Umezawa Kouta , Yama Kazuma , Aita Yuto , Ichiba Yuko , Murakami Shinnosuke , Kakizawa Yasushi , Kumagai Takashi , Yamada Takuji , Fukuda Shinji
Published: November 2019

Epidemiological studies using saliva have revealed relationships between the oral microbiome and many oral and systemic diseases. However, when collecting from a large number of participants such as a large-scale cohort study, the time it takes to collect saliva can be a problem. Mouth-rinsed water, which is water that has been used to rinse the oral cavity, can be used as an alternative method for collecting saliva for oral microbiome analysis because it can be collected in a shorter time than saliva. The purpose of this study was to verify whether mouth-rinsed water is a suitable saliva substitute for analyzing the oral microbiome. We collected samples of mouth-rinsed water, stimulated saliva, unstimulated saliva, and tongue coating from 10 systemic healthy participants, and compared the microbial diversity and composition of the samples using next-generation sequencing of 16S rRNA-encoding genes. The results showed that the microbial diversity of mouth-rinsed water was similar to that of unstimulated and stimulated saliva, and significantly higher than that of tongue-coating samples. The microbial composition at the species level of mouth-rinsed water also showed a very high correlation with the composition of unstimulated and stimulated saliva. These results suggest that the mouth-rinsed water is a suitable collection method instead of saliva for oral microbiome analysis.
Ecotypic changes of alpine birds to climate change
Authors: Delgado Maria del Mar , Bettega Chiara , Martens Jochen , Päckert Martin
Published: November 2019

In endotherm animals, several traits are related to climate. For example, Bergmann’s rule predicts a decrease in body size within species and across closely related species with increasing temperature, whereas Gloger’s rule states that birds and mammals should be darker in humid and warm environments compared to colder and drier areas. However, it is still not clear whether ecotypic responses to variation in the local environment can also apply to morphological and colouration changes through time in response to climate change. We present a 100-year-long time series on morphological and melanin-based colours of snowfinch (325 Montifringilla, 92 Pyrgilauda and 30 Onychostruthus) museum specimens. Here we show that the tarsus length of the species has decreased and the saturation of the melanin-based colour has increased, which was correlated with the increase of temperature and precipitations. As ecotypic variations are tightly linked to individual behavioural and physiological responses to environmental variations, differently sized and coloured individuals are expected to be differently penalized by global changes. This study opens the pertinent question about whether ecotypic responses can enhance population persistence in the context of global change.
Influence of Periodontal Disease on cardiovascular markers in Diabetes Mellitus patients
Authors: Pedroso Juliana de Fatima , Lotfollahi Zahra , Albattarni Ghadeer , Arrruda Schulz Maiara , Monteiro Andrea , Sehnem Andre Luiz , Gidlund Magnus Ake , Figueiredo Neto Antonio Martins , Jardini Maria Aparecida Neves
Published: November 2019

The objective of the present study was to establish if individuals with Diabetes Mellitus (DM2) and periodontal diseases (gingivitis or periodontitis) presented an increase in the concentration of modified LDL (moLDL) and what is the influence of periodontal treatment on the decrease of moLDL particles with consequent improvement in the parameters of DM2. Twenty-four diabetic patients with periodontitis (Group 1) and twenty-four diabetic patients with gingivitis (Group 2) were followed up for a period of 12 months. Group 1 was treated with periodontal debridement, and Group 2 received supra-gingival scaling and prophylaxis. In both groups, periodontal clinical parameters: probing depth (PD), clinical attachment level (CAL), gingival resection (GR), bleeding on probing index (BOP) and plaque index; inflammatory serum markers (glycemia, A1c, total cholesterol, HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c), triglycerides and hs-CRP) and oxidized LDL (oxLDL) were measured at baseline, t = 6 and t = 12 months after treatment. Solutions of LDL were analyzed using the nonlinear optical Z-Scan and optical absorption techniques. The periodontal clinical parameters showed significant improvement (p < 0.05) in both Group after 12 months. For both groups, total cholesterol, HDL-c, LDL-c, triglycerides and A1c levels did not show significant reductions after periodontal therapy. hs-CRP levels in Group 1 presented a significant reduction after 12 months. The glycemic rate and the oxLDL concentrations did not show significant differences as a function of time. The optical measurements of LDL solutions revealed an improvement of the LDL-c quality in both groups. Periodontal debridement was able to improve periodontal parameters and the quality of LDL-c in diabetic patients but without changes in the oxLDL concentration in both groups. Considering the clinical relevance, the reduction of infectious and inflammatory sites present in the oral cavity through periodontal therapy may help with the control and prevention of hyperglycemia and precursors of cardiovascular diseases.
Hif1a and Hif2a can be safely inactivated in cone photoreceptors
Authors: Samardzija Marijana , Barben Maya , Todorova Vyara , Klee Katrin , Storti Federica , Grimm Christian
Published: November 2019

Impaired tissue oxygenation results in hypoxia and leads to the activation of hypoxia-inducible transcription factors (HIF). A chronic, HIF-triggered molecular response to hypoxia may be an important factor in the etiology of age-related macular degeneration (AMD) and is likely activated before any clinical manifestation of the disease. Thus, HIF1 and HIF2 recently emerged as potential therapeutic targets for AMD. To address and evaluate potential consequences of anti-HIF therapies for retinal physiology and function, we generated mouse lines that have Hif1a, or both Hif1a and Hif2a ablated specifically in cone photoreceptors. The knockdown of Hifs in cones did not cause detectable pathological alterations such as loss of cone photoreceptors, retinal degeneration or abnormalities of the retinal vasculature, had no impact on retinal function and resulted in a similar tolerance to hypoxic exposure. Our data indicate that HIF transcription factors are dispensable for maintaining normal cone function and survival in retinas of adult mice. This study provides the groundwork necessary to establish safety profiles for strategies aiming at antagonizing HIF1A and HIF2A function in cone photoreceptors for the treatment of retinal degenerative diseases that involve a hypoxic component such as AMD.
Parkin truncating variants result in a loss-of-function phenotype
Authors: Santos Mariana , Morais Sara , Pereira Conceição , Sequeiros Jorge , Alonso Isabel
Published: November 2019

Parkinson disease (PD) is the second most common neurodegenerative disorder. Most cases of PD are sporadic, while 5–10% have a known genetic basis. Variants in the PARK2 gene are the most frequent cause of autosomal recessive juvenile-onset PD. PARK2 encodes parkin, a multi-domain protein that functions as an ubiquitin E3 ligase. Numerous variants spanning all parkin domains have been identified, although the pathogenic relevance for several of those remains unclear. In this study, we aimed to functionally characterize two truncating parkin variants: N52Mfs*29, which is highly prevalent in the Portuguese and Spanish populations, and L358Rfs*77, recently identified in the Portuguese population. Our results indicate that both variants are prematurely degraded by the proteasome, even though proteins levels are still moderate. We also showed that they are aggregation-prone and lead to mislocalized parkin. Interestingly, the L358Rfs*77 variant is mislocalized to the nucleus, which was never reported for parkin variants. While N52Mfs*29 impaired self-ubiquitination activity, the L358Rfs*77 variant seemed to retain it. Both variants, however, fail to ubiquitinate p62 substrate and did not relocalize to depolarized mitochondria. Therefore, we conclude that parkin truncating variants cause loss of parkin function, thus showing their causative role in PD pathogenesis.
Realising the potential of Natura 2000 to achieve EU conservation goals as 2020 approaches
Authors: Hermoso Virgilio , Morán-Ordóñez Alejandra , Canessa Stefano , Brotons Lluis
Published: November 2019

In the last decades the EU has made substantial efforts implementing conservation strategies to halt biodiversity loss. However, little improvement has been reported. Given the proximity of the 2020 landmark set by the EU Biodiversity Strategy and the Convention for Biological Diversity, alternatives to reduce this conservation gap and prospect future strategies must be assessed urgently. Here, we explore how the current Natura 2000 could be used to enhance management of terrestrial and freshwater threatened vertebrates. We identified Natura 2000 sites to increase the coverage of threatened species as target species under two alternative scenarios: a policy-driven approach including only threatened vertebrates listed in the Directives; and a conservation-driven approach, including all the remaining threatened vertebrates. We show that representation of threatened vertebrates in Natura 2000 could be improved by updating lists of target species in less than 1% and 3% of sites in the policy-driven and conservation-driven scenarios, respectively. We highlight the strength of Natura 2000, with sites that complement each other and could contribute to achieving more ambitious conservation targets under future strategies. Prioritisation exercises like this could help realise the potential of this network and enhance the management of threatened species and improve current gaps.
Deep soil C and N pools in long-term fenced and overgrazed temperate grasslands in northwest China
Authors: Li Jian-Ping , Ma Hong-Bin , Xie Ying-Zhong , Wang Kai-Bo , Qiu Kai-Yang
Published: November 2019

Fencing for grazing exclusion has been widely found to have an impact on grassland soil organic carbon (SOC) and total nitrogen (TN), but little is known about the impact of fenced grassland on the changes in deep soil carbon (C) and nitrogen (N) stocks in temperate grasslands. We studied the influence of 30 years fencing on vegetation and deep soil characteristics (0–500 cm) in the semi-arid grasslands of northern China. The results showed that fencing significantly increased the aboveground biomass (AGB), litter biomass (LB), total biomass, vegetation coverage and height, and soil water content and the SOC and TN in the deep soil. The belowground biomass (BGB) did not significantly differ between the fenced and grazed grassland. However, fencing significantly decreased the root/shoot ratio, forbs biomass, pH, and soil bulk density. Meanwhile, fencing has significantly increased the C and N stocks in the AGB and LB but not in the BGB. After 30 years of fencing, the C and N stocks significantly increased in the 0–500 cm soil layer. The accumulation of SOC mainly occurred in the deep layers (30–180 cm), and the accumulation of TN occurred in the soil layers of 0 to 60 cm and 160 to 500 cm. Our results indicate that fencing is an effective way to improve deep soil C and N stocks in temperate grassland of northwest China. There were large C and N stocks in the soil layers of 100 to 500 cm in the fenced grasslands, and their dynamics should not be ignored.
Cold Atmospheric Plasma-Activated Water Irrigation Induces Defense Hormone and Gene expression in Tomato seedlings
Authors: Adhikari Bhawana , Adhikari Manish , Ghimire Bhagirath , Park Gyungsoon , Choi Eun Ha
Published: November 2019

Plants are very vulnerable to pathogen attacks and environmental stress as they are exposed to harsh environments in natural conditions. However, they have evolved a self-defense system whereby reactive oxygen and nitrogen species (RONS) act as double-edged swords by imposing (at higher concentration) and mitigating (at lower concentration) environmental stress. Cold plasma is emerging as a feasible option to produce a variety of RONS in a controlled manner when amalgamate with water. Cold plasma activated/treated water (PAW) contains a variety of RONS at concentrations, which may help to activate the plant’s defense system components. In the present study, we examine the effect of cold atmospheric-air jet plasma exposure (15 min, 30 min, and 60 min) on the water’s RONS level, as well as the impact of PAW irrigation, (assigned as 15PAW, 30PAW, and 60PAW) on tomato seedlings growth and defense response. We found that PAW irrigation (priming) upregulate seedlings growth, endogenous RONS, defense hormone (salicylic acid and jasmonic acid), and expression of key pathogenesis related (PR) gene. 30 min PAW contains RONS at concentrations which can induce non-toxic signaling. The present study suggests that PAW irrigation can be beneficial for agriculture as it modulates plant growth as well as immune response components.
Highly sensitive immunosensing platform for one-step detection of genetically modified crops
Authors: Gao Hongfei , Wen Luke , Hua Wei , Tian Jing , Lin Yongjun
Published: November 2019

The wide cultivation of genetically modified (GM) insect-resistant crops has raised concerns on the risks to the eco-environment resulting from a release of Cry proteins. Therefore, it is vital to develop a method for the quantification of GM crops. Herein, A highly sensitive immunosensing platform has been developed for both colorimetric and chemiluminescent (CL) detection of Cry 1Ab using dual-functionalized gold nanoparticles (AuNPs) as signal amplification nanoprobes for the first time. In this work, anti-Cry 1Ab monoclonal antibody and horseradish peroxidase (HRP) are simultaneously functionalized on the surface of AuNPs with an exceptionally simple synthesis method. Combined with immunomagnetic separation, this immunosensing platform based on colorimetric method could detect Cry 1Ab in one step in a linear range from 1.0 to 40 ng mL−1 within 1.5 h, with a limit of detection of 0.50 ng mL−1. The sensitivity of fabricated nanoprobes was 15.3 times higher than that using commercial HRP-conjugated antibody. Meanwhile, the fabricated nanoprobes coupled with CL detection was successfully applied for Cry 1Ab detection with a minimum detection concentration of 0.050 ng mL−1 within a linear range of 0.10–20 ng mL−1. The proposed approach was validated with genuine GM crops, and the results showed a good correlation coefficient of 0.9906 compared to those of a commercial ELISA kit. Compared with ELISA, the developed immunosensing platform significantly simplified the assay procedure and shortened the analytical time, thus providing a new platform for the detection of genetically modified crops with high sensitivity, rapidity and simplicity.
China’s Non-CO2 Greenhouse Gas Emissions: Future Trajectories and Mitigation Options and Potential
Authors: Lin Jiang , Khanna Nina , Liu Xu , Teng Fei , Wang Xin
Published: November 2019

Forecasts indicate that China’s non-carbon dioxide (CO2) greenhouse gas (GHG) emissions will increase rapidly from the 2014 baseline of 2 billion metric tons of CO2 equivalent (CO2e). Previous studies of the potential for mitigating non-CO2 GHG emissions in China have focused on timeframes through only 2030, or only on certain sectors or gases. This study uses a novel bottom-up end-use model to estimate mitigation of China’s non-CO2 GHGs under a Mitigation Scenario whereby today’s cost-effective and technologically feasible CO2 and non-CO2 mitigation measures are deployed through 2050. The study determines that future non-CO2 GHG emissions are driven largely by industrial and agricultural sources and that China could reduce those emissions by 47% by 2050 while enabling total GHG emissions to peak by 2023. Except for F-gas mitigation, few national or sectoral policies have focused on reducing non-CO2 GHGs. Policy, market, and other institutional support are needed to realize the cost-effective mitigation potentials identified in this study.
Fall Risk Prediction in Multiple Sclerosis Using Postural Sway Measures: A Machine Learning Approach
Authors: Sun Ruopeng , Hsieh Katherine L. , Sosnoff Jacob J.
Published: November 2019

Numerous postural sway metrics have been shown to be sensitive to balance impairment and fall risk in individuals with MS. Yet, there are no guidelines concerning the most appropriate postural sway metrics to monitor impairment. This investigation implemented a machine learning approach to assess the accuracy and feature importance of various postural sway metrics to differentiate individuals with MS from healthy controls as a function of physiological fall risk. 153 participants (50 controls and 103 individuals with MS) underwent a static posturography assessment and a physiological fall risk assessment. Participants were further classified into four subgroups based on fall risk: controls, low-risk MS (n = 34), moderate-risk MS (n = 27), high-risk MS (n = 42). Twenty common sway metrics were derived following standard procedures and subsequently used to train a machine learning algorithm (random forest – RF, with 10-fold cross validation) to predict individuals’ fall risk grouping. The sway-metric based RF classifier had high accuracy in discriminating controls from MS individuals (>86%). Sway sample entropy was identified as the strongest feature for classification of low-risk MS individuals from healthy controls. Whereas for all other comparisons, mediolateral sway amplitude was identified as the strongest predictor for fall risk groupings.