bluuebunny/crossref_metadata_2025 huggingface dataset:
Flexibility and Resilience in Corporate Decision Making: A New Sustainability-Based Risk Management System in Uncertain Times
Authors: Settembre-Blundo Davide , González-Sánchez Rocío , Medina-Salgado Sonia , García-Muiña Fernando E.
Published: August 2021

Risk management plays a key role in uncertain times, preventing corporations from acting rashly and incorrectly, allowing them to become flexible and resilient. A global turbulence such as the COVID-19 pandemic has had a strong impact on individual companies and entire economic sectors, raising the question of whether a paradigm shift is necessary, in order to enable a new cycle of development that is much environmentally, socially and economically sustainable. This environmental and socio-economic context of profound uncertainty forces organizations to consider more carefully the risk factors affecting their business continuity, as well as how these factors relate to sustainability issues. However, there is a gap in knowledge about how risk management systems relate to sustainability management systems, and how both of them exert influence on business performance, especially from a theoretical point of view. The aim of this study is to address this gap, by developing a new interpretative framework for the analysis of risk management strategies in organizations. This approach has been identified in economic hermeneutics as an innovative methodological tool to improve the knowledge of risk and design the most appropriate management strategies. The paper provides two main results: the first one is the construction of a theoretical model that relates risk management to sustainability management; the second one is an operational framework of multidimensional risk assessment useful for analysis at different levels (business, competitive scenario and system). Finally, the model also makes it possible to carry out a sustainability assessment through risk evaluation in the perspective of the sustainable development goals.
Newer results of Monte Carlo inversion of IP data in water base protection and ore exploration
Authors: Turai Endre , Turtogtokh Byambasuren , Dobróka Mihály , Baracza Mátyás Krisztián
Published: August 2021

The paper presents the latest results of Monte Carlo inversion of IP data in the areas of water base protection and ore exploration. The method of determining the time constant spectrum using Monte Carlo inversion and the parameters characterizing the degree of environmental contaminations and ore deposition are presented. Among the field applications in Hungary, the investigation of the ionic pollution of the Ráckeve water base and the characterization of the Felsőtelekes waste dump of the Rudabánya iron ore mine are presented. In addition to these, the paper presents the investigation of ore deposition in the area of a gold mine in Mongolia using the Monte Carlo inversion of multi-electrode pole-dipole IP method.
Identification and Quantification of Node Criticality through EWM–TOPSIS: A Study of Hong Kong’s MTR System
Authors: Zhang Yifan , Ng S. Thomas
Published: August 2021

Public transport networks (PTNs) are critical in populated and rapidly densifying cities such as Hong Kong, Beijing, Shanghai, Mumbai, and Tokyo. Public transportation plays an indispensable role in urban resilience with an integrated, complex, and dynamically changeable network structure. Consequently, identifying and quantifying node criticality in complex PTNs is of great practical significance to improve network robustness from damage. Despite the proposition of various node criticality criteria to address this problem, few succeeded in more comprehensive aspects. Therefore, this paper presents an efficient and thorough ranking method, that is, entropy weight method (EWM)–technology for order preference by similarity to an ideal solution (TOPSIS), named EWM–TOPSIS, to evaluate node criticality by taking into account various node features in complex networks. Then we demonstrate it on the Mass Transit Railway (MTR) in Hong Kong by removing and recovering the topkcritical nodes in descending order to compare the effectiveness of degree centrality (DC), betweenness centrality (BC), closeness centrality (CC), and the proposed EWM–TOPSIS method. Four evaluation indicators, that is, the frequency of nodes with the same ranking (F), the global network efficiency (E), the size of the largest connected component (LCC), and the average path length (APL), are computed to compare the performance of the four methods and measure network robustness under different designed attack and recovery strategies. The results demonstrate that the EWM–TOPSIS method has more obvious advantages than the others, especially in the early stage.
Distribution patterns of the native Eurasian and the non-native North American beaver in Finland—possible factors affecting the slow range expansion of the native species
Authors: Alakoski Riikka , Kauhala Kaarina , Selonen Vesa
Published: August 2021

Distribution patterns of species are affected by resource availability, dispersal, disturbance and population dynamics. The smaller population size and range of the native Eurasian beaver (Castor fiber) compared to the non-native North American beaver (Castor canadensis) in Finland raise questions on reasons for the slower range expansion of the native species. We compared the population growth rates and the spread of both species from their release sites. We also studied the factors possibly affecting the spread of the Eurasian beaver in South western Finland in more detail. We found that the North American beaver has spread longer distances than the Eurasian beaver, but we did not find evidence for movement barriers constraining the expansion rate of the native species. Lack of high-quality habitats does not seem to constrain the expansion to nearby areas either. Despite this, the Eurasian beaver population has grown to a high density close to its reintroduction site, and it has started to spread to novel areas only recently. We conclude that the expansion of the native beaver in Finland seems to be controlled by factors other than those related to barriers for movement: movement behavior and population dynamics, which require further investigation.
Classifying disequilibrium of small mountain glaciers from patterns of surface elevation change distributions
Authors: Hartl Lea , Helfricht Kay , Stocker-Waldhuber Martin , Seiser Bernd , Fischer Andrea
Published: August 2021

The overall trend of rapid retreat of Alpine glaciers contains considerable variability of responses at the scale of individual glaciers. As a step towards a regional assessment of glacier state that allows a detailed differentiation of single glaciers, we explore the potential of a self-organizing maps (SOM) algorithm to identify and cluster recurring patterns of thickness change at glaciers in western Austria. Using digital elevation models and glacier inventories for three time periods, we compute the frequency distribution of surface elevation change over the area of each glacier in the data set, for each period. The results of the SOM clustering show a distinct pattern shift over time: From 1969 to 1997, surface elevation change occurred at relatively uniform rates across a given glacier. Since 1997, the distribution of surface elevation change at individual glaciers has been far less uniform, indicating accelerated processes of disintegration. Tracking the evolution of individual glaciers throughout the time periods via the clusters highlights both the broader regional trend as well as glaciers that deviate from this trend, e.g. some very small, high elevation glaciers that have reverted to reduced and more uniform volume loss patterns.
Effect of the BCAT2 polymorphism (rs11548193) on plasma branched-chain amino acid concentrations after dietary intervention in subjects with obesity and insulin resistance
Authors: González-Salazar Luis E. , Granados-Portillo Omar , Medina-Vera Isabel , Pichardo-Ontiveros Edgar , Vigil-Martínez Ana , Guizar-Heredia Rocío , Palacios-González Berenice , Arteaga-Sánchez Liliana , Hernández-Gómez Karla G. , Avila-Nava Azalia , Serralde-Zúñiga Aurora E. , Flores-López Adriana , Noriega Lilia G. , Torres Nimbe , Olin-Sandoval Viridiana , Vázquez-Manjarrez Natalia , Domínguez-Velázquez Natali , Reyes-García Juan G. , Tovar Armando R. , Guevara-Cruz Martha
Published: August 2021

Branched-chain amino acids (BCAA) are considered markers of insulin resistance (IR) in subjects with obesity. In this study, we evaluated whether the presence of the SNP of the branched-chain aminotransferase 2 (BCAT2) gene can modify the effect of a dietary intervention (DI) on the plasma concentration of BCAA in subjects with obesity and IR. A prospective cohort study of adult subjects with obesity, BMI ≥ 30 kg/m2, homeostatic model assessment-insulin resistance (HOMA-IR ≥ 2·5) no diagnosed chronic disease, underwent a DI with an energy restriction of 3140 kJ/d and nutritional education for 1 month. Anthropometric measurements, body composition, blood pressure, resting energy expenditure, oral glucose tolerance test results, serum biochemical parameters and the plasma amino acid profile were evaluated before and after the DI. SNP were assessed by the TaqMan SNP genotyping assay. A total of eighty-two subjects were included, and fifteen subjects with a BCAT2 SNP had a greater reduction in leucine, isoleucine, valine and the sum of BCAA. Those subjects also had a greater reduction in skeletal muscle mass, fat-free mass, total body water, blood pressure, muscle strength and biochemical parameters after 1 month of the DI and adjusting for age and sex. This study demonstrated that the presence of the BCAT2 SNP promotes a greater reduction in plasma BCAA concentration after adjusting for age and sex, in subjects with obesity and IR after a 1-month energy-restricted DI.
The hatching gland cells of trout embryos: characterisation of
N- and O-linked oligosaccharides
Authors: DE GASPAR IGNACIO , BLANQUEZ MARIA JOSE , FRAILE BENITO , PANIAGUA RICARDO , ARENAS MARIA ISABEL
Published: August 2021

A histochemical, light and electron microscopy study of the hatching
gland cells (HGCs) in incubated 50-d-old trout embryos is reported. The distribution of carbohydrate residues
in the glycoconjugates of these cells
was studied by means of a battery of 13 different lectins conjugated with
horseradish peroxidase (PNA,
ConA, LCA, WGA, SBA, UEA-I, HPA, DBA) or digoxigenin (DSA, MAA, AAA, SNA,
GNA).
Identification of N- and O-linked oligosaccharides in HGCs was performed
by application of both chemical
and enzymatic treatments. Present results suggest that HGCs are seromucous
cells which store both high
choriolytic enzyme (HCE) and low choriolytic enzyme (LCE), and that their
cytoplasmic granules,
endoplasmic reticulum and Golgi complex contain additional sialic acid-rich
glycoproteins. The negative
charge of these glycoproteins might be responsible for the rapid expansion
of mucin to form a highly
hydrated gel, which would facilite the action of these enzymes in programmed
cell death and might play a
major role during the morphogenic events.
Clinging to survival: Critically Endangered Chapman's pygmy chameleon Rhampholeon chapmanorum persists in shrinking forest patches
Authors: Tolley Krystal A. , Tilbury Colin R. , da Silva Jessica M. , Brown Gary , Chapeta Yankho , Anderson Christopher V.
Published: August 2021

The Critically Endangered Chapman's pygmy chameleon Rhampholeon chapmanorum is endemic to the low elevation rainforest of the Malawi Hills in southern Malawi. Much of this forest has been converted to agriculture and it was uncertain whether chameleon populations have persisted. We used current and historical satellite imagery to identify remaining forest patches and assess deforestation. We then surveyed forest patches for the presence of this chameleon, and assessed its genetic diversity and structure. We estimated that 80% of the forest has been destroyed since 1984, although we found extant populations of the chameleon in each of the patches surveyed. Differentiation of genetic structure was strong between populations, suggesting that gene flow has been impaired. Genetic diversity was not low, but this could be the result of a temporal lag as well as lack of sensitivity in the mitochondrial marker used. Overall, the impact of forest loss is assumed to have led to a large demographic decline, with forest fragmentation preventing gene flow.
Optimising aircraft taxi speed: Design and evaluation of new means to present information on a head-up display
Authors: Eklund Rikard , Osvalder Anna-Lisa
Published: August 2021

The objective of this study was to design and evaluate new means of complying to time constraints by presenting aircraft target taxi speeds on a head-up display (HUD). Four different HUD presentations were iteratively developed from paper sketches into digital prototypes. Each HUD presentation reflected different levels of information presentation. A subsequent evaluation included 32 pilots, with varying flight experience, in usability tests. The participants subjectively assessed which information was most useful to comply with time constraints. The assessment was based on six themes including information, workload, situational awareness, stress, support and usability. The evaluation consisted of computer-simulated taxi-runs, self-assessments and statistical analysis. Information provided by a graphical vertical tape descriptive/predictive HUD presentation, including alpha-numerical information redundancy, was rated most useful. Differences between novice and expert pilots can be resolved by incorporating combinations of graphics and alpha-numeric presentations. The findings can be applied for further studies of combining navigational and time-keeping HUD support during taxi.
Revisiting Online and Offline Data Assimilation Comparison for Paleoclimate Reconstruction: An Idealized OSSE Study
Authors: Okazaki Atsushi , Miyoshi Takemasa , Yoshimura Kei , Greybush Steven J. , Zhang Fuqing
Published: August 2021

Data assimilation (DA) has been applied to estimate the time‐mean state, such as annual mean surface temperature for paleoclimate reconstruction. There are two types of DA for this purpose: online‐DA and offline‐DA. The online‐DA estimates both time‐mean states (analyses) and initial conditions for subsequent DA cycles, while the offline‐DA only estimates the time‐mean analyses. If there is sufficiently long predictability in the system of interest compared to the temporal resolution of the observations, online‐DA is expected to outperform offline‐DA by utilizing information in the initial conditions. However, previous studies failed to show the superiority of online‐DA when time‐averaged observations are assimilated, and the reason has not been investigated thoroughly. This study compares online‐DA and offline‐DA and investigates the relation to the predictability using an intermediate complexity general circulation model with perfect‐model observing system simulation experiments. The result shows that the online‐DA outperforms offline‐DA when the length of predictability is longer than the averaging time of the observations. We also found that the longer the predictability, the more skillful the online‐DA. Here, the ocean plays a crucial role in extending predictability, which helps online‐DA to outperform offline‐DA. Interestingly, the observations of near‐surface air temperature over land are highly valuable to update the ocean variables in the analysis steps, suggesting the importance of using cross‐domain covariance information between the atmosphere and the ocean when online‐DA is applied to reconstruct paleoclimate.
Arctic Cloud Response to a Perturbation in Sea Ice Concentration: The North Water Polynya
Authors: Monroe Emily E. , Taylor Patrick C. , Boisvert Linette N.
Published: August 2021

Surface and atmosphere energy exchanges play an important role in the Arctic climate system by influencing the lower atmospheric stability and humidity, sea ice melt and growth, and surface temperature. Sea ice significantly alters the character of these energy exchanges relative to ice‐free ocean. The observed decline in Arctic sea ice since 1979 motivates questions related to the evolving role of surface‐atmosphere coupling and potential feedbacks on the Arctic system. Due to the strong wintertime cloud warming effect, a critical question concerns the potential response of low clouds to Arctic sea ice decline. Previous approaches relied on interannual variability to investigate the cloud response to sea ice decline. However, the covariation between atmospheric conditions and sea ice makes it difficult to define an observational control when using interannual variability. To circumvent this difficulty, we exploit the recurring North Water polynya, an episodic opening in the northern Baffin Bay sea ice, as a natural laboratory to isolate the cloud response to a rapid, near‐step perturbation in sea ice. Our results show that during the event, (a) low‐cloud cover is 10%–33% larger over the polynya than nearby sea ice, (b) cloud liquid water content is up to 400% larger over the polynya than nearby sea ice, and (c) the surface cloud radiative effect is 18 W m−2 larger over the polynya than nearby sea ice. Our results provide evidence that the low‐cloud response during a polynya is a positive feedback lengthening the event.
Biofuels Reserve Controlled Wildfire Regimes Since the Last Deglaciation: A Record From Gonghai Lake, North China
Authors: Ji Panpan , Chen Jianhui , Zhou Aifeng , Ma Rui , Chen Ruijin , Chen Shengqian , Lv Feiya , Ding Guoqiang , Liu Yan , Chen Fahu
Published: August 2021

Wildfire activity is an important activity in evolution of vegetation and carbon cycling. Whether wet weather will suppress wildfire or promote them by increasing fuel reserves during the Holocene is not clear. We obtained a record of black carbon from a sediment core spanning the last 14.8 kyr from Gonghai Lake, in North China. There is a close relationship between the timing of wildfire activity and vegetation development driven by the East Asian summer monsoon intensity. On a millennial timescales, wet climatic conditions provide a sufficient biofuels reserve, in the same period wildfire increase; thus, the regional potential biofuels reserve is shown to be an important controlling of regional wildfire activity in the monsoon region of China, under natural conditions. We infer that with the strengthening of Asian summer monsoon caused by global warming, the wildfire carbon emission in Asian monsoon region may increase in the future.
Coordinated and Competitive Formation of Soil Magnetic Particles Driven by Contrary Climate Development
Authors: Cai Yunfeng , Long Xiaoyong , Meng Xianqiang , Ji Junfeng , Wang Yong , Xie Shiyou
Published: August 2021

Ferrimagnetic (FM) and antiferromagnetic (AFM) iron oxide particles are considered pedogenic and climatic indicators due to their enrichment with comparable increasing in rainfall and temperature. However, the opposite changes in rainfall and temperature result in rapid change of relative humidity (RH), which could lead to their competition and transformation. We examined two soil sequences which have undergone contrary climate development on the eastern edge of the Tibetan Plateau. Dry and warm climate with low RH favors the coordinative enrichment of AFM hematite and FM particles, while wet and cool climate with high RH mainly produces goethite but leads to competition between low content AFM hematite and FM particles. The outcome well interprets the changing relationship between color and magnetism in soils and sediments, and suggests that temperature is as important as precipitation in paleoclimate reconstruction based on iron oxides, especially during strong dry‐wet cycles and climate pattern shifts.
Seismic Constraint From Vp/Vs Ratios on the Structure and Composition Across the Continent‐Ocean Transition Zone, South China Sea
Authors: Li Yuhan , Grevemeyer Ingo , Huang Haibo , Qiu Xuelin , Xu Ziying
Published: August 2021

At non‐volcanic passive continental margins, seismic techniques often failed to uniquely define the nature of crustal domains. Here, we overcome this problem by studying the structure and composition of the continent‐ocean transition (COT) in the Southwest Sub‐basin of the South China Sea, using P and S wave seismic tomography and Vp/Vs ratios, providing unique constraints on lithology. Throughout the image domain, we can rule out large areas of exhumed mantle as Vp/Vs ratios are always <1.9 in the shallow basement layer. Instead, the COT is characterized by extended and fragmented continental crust, and possibly mafic aggregation at the bottom of the crust. In concert with observations from multichannel seismic reflection data, seismic velocities and Vp/Vs ratios suggest that the oldest oceanic crust was formed by starved magmatism, causing rugged basement, thin crust, nearly absent lower crust, and moderately serpentinized mantle below. Our results reveal that rifting occurred without un‐roofing continental mantle.
Radar Observation of Extreme Vertical Drafts in the Polar Summer Mesosphere
Authors: Chau J. L. , Marino R. , Feraco F. , Urco J. M. , Baumgarten G. , Lübken F.‐J. , Hocking W. K. , Schult C. , Renkwitz T. , Latteck R.
Published: August 2021

The polar summer mesosphere is the Earth's coldest region, allowing the formation of mesospheric ice clouds. These ice clouds produce strong polar mesospheric summer echoes (PMSE) that are used as tracers of mesospheric dynamics. Here, we report the first observations of extreme vertical drafts (50 ) in the mesosphere obtained from PMSE, characterized by velocities more than five standard deviations larger than the observed vertical wind variability. Using aperture synthesis radar imaging, the observed PMSE morphology resembles a solitary wave in a varicose mode, narrow along propagation (3–4 km) and elongated ( km) transverse to propagation direction, with a relatively large vertical extent (13 km). These spatial features are similar to previously observed mesospheric bores, but we observe only one crest with much larger vertical extent and higher vertical velocities.
Impact of the Stratospheric Ozone on the Northern Hemisphere Surface Climate During Boreal Winter
Authors: Jeong Yong‐Cheol , Yeh Sang‐Wook , Lee Seungun , Park Rokjin J. , Son Seok‐Woo
Published: August 2021

In this study, we examine the impact of stratospheric ozone on the Northern Hemisphere (NH) surface climate during boreal winter by analyzing the two experiments using Global/Regional Integrated Model system‐Chemistry Climate Model (GRIMs‐CCM) (i.e., LINOZ‐on/‐off experiments) and eight Atmosphere Model Inter‐comparison Project (AMIP) climate models. In LINOZ‐on, ozone concentration in the upper troposphere and lower stratosphere (UTLS) varies with latitudes, being low in the tropics and high in the mid‐to‐high‐latitudes, by adopting a linearized ozone scheme. The LINOZ‐off, however, prescribes constant ozone concentration throughout all latitudes. Cooler surface temperatures over the Eurasian and Asian continents in boreal winter are simulated in LINOZ‐on than that in LINOZ‐off. A reduced mean UTLS temperature gradient in LINOZ‐on, due to the difference of climatological mean ozone concentration, causes a weakened mean zonal wind in the lower stratosphere compared to the LINOZ‐off. This mean wind difference is extended all the way to the surface, resulting in a negative Arctic Oscillation (AO)‐like mean state in the mid‐to‐high latitudes in the LINOZ‐on. Subsequently, it causes cool surface temperatures over the Eurasian and Asian continents by altering horizontal winds. This result is also supported by the comparison between AMIP models with a relatively high and low stratospheric ozone concentration in the mid‐to‐high latitudes. Therefore, a careful attention should be paid to the climatology of stratospheric ozone concentration in climate models to correctly simulate surface climate in the NH in the past and future climate.
RNF141 interacts with KRAS to promote colorectal cancer progression
Authors: Zhang Jiuna , Jiang Xiaoyu , Yin Jie , Dou Shiying , Xie Xiaoli , Liu Ting , Wang Yijun , Wang Shuling , Zhou Xue , Zhang Dongxuan , Jiang Huiqing
Published: August 2021

RING finger proteins (RNFs) play a critical role in cancer initiation and progression. RNF141 is a member of RNFs family; however, its clinical significance, roles, and mechanism in colorectal cancer (CRC) remain poorly understood. Here, we examined the expression of RNF141 in 64 pairs of CRC and adjacent normal tissues by real-time PCR, Western blot, and immunohistochemical analysis. We found that there was more expression of RNF141 in CRC tissue compared with its adjacent normal tissue and high RNF141 expression associated with T stage. In vivo and in vitro functional experiments were conducted and revealed the oncogenic role of RNF141 in CRC. RNF141 knockdown suppressed proliferation, arrested the cell cycle in the G1 phase, inhibited migration, invasion and HUVEC tube formation but promoted apoptosis, whereas RNF141 overexpression exerted the opposite effects in CRC cells. The subcutaneous xenograft models showed that RNF141 knockdown reduced tumor growth, but its overexpression promoted tumor growth. Mechanistically, liquid chromatography-tandem mass spectrometry indicated RNF141 interacted with KRAS, which was confirmed by Co-immunoprecipitation, Immunofluorescence assay. Further analysis with bimolecular fluorescence complementation (BiFC) and Glutathione-S-transferase (GST) pull-down assays showed that RNF141 could directly bind to KRAS. Importantly, the upregulation of RNF141 increased GTP-bound KRAS, but its knockdown resulted in a reduction accordingly. Next, we demonstrated that RNF141 induced KRAS activation via increasing its enrichment on the plasma membrane not altering total KRAS expression, which was facilitated by the interaction with LYPLA1. Moreover, KRAS silencing partially abolished the effect of RNF141 on cell proliferation and apoptosis. In addition, our findings presented that RNF141 functioned as an oncogene by upregulating KRAS activity in a manner of promoting KRAS enrichment on the plasma membrane in CRC.
Selective inhibition of HDAC6 regulates expression of the oncogenic driver EWSR1-FLI1 through the EWSR1 promoter in Ewing sarcoma
Authors: García-Domínguez Daniel J. , Hajji Nabil , Sánchez-Molina Sara , Figuerola-Bou Elisabet , de Pablos Rocío M. , Espinosa-Oliva Ana M. , Andrés-León Eduardo , Terrón-Camero Laura Carmen , Flores-Campos Rocío , Pascual-Pasto Guillem , Robles María José , Machado Isidro , Llombart-Bosch Antonio , Magagnoli Giovanna , Scotlandi Katia , Carcaboso Ángel M. , Mora Jaume , de Álava Enrique , Hontecillas-Prieto Lourdes
Published: August 2021

Ewing sarcoma (EWS) is an aggressive bone and soft tissue tumor of children and young adults in which the principal driver is a fusion gene, EWSR1-FLI1. Although the essential role of EWSR1-FLI1 protein in the regulation of oncogenesis, survival, and tumor progression processes has been described in-depth, little is known about the regulation of chimeric fusion-gene expression. Here, we demonstrate that the active nuclear HDAC6 in EWS modulates the acetylation status of specificity protein 1 (SP1), consequently regulating the SP1/P300 activator complex binding to EWSR1 and EWSR1-FLI1 promoters. Selective inhibition of HDAC6 impairs binding of the activator complex SP1/P300, thereby inducing EWSR1-FLI1 downregulation and significantly reducing its oncogenic functions. In addition, sensitivity of EWS cell lines to HDAC6 inhibition is higher than other tumor or non-tumor cell lines. High expression of HDAC6 in primary EWS tumor samples from patients correlates with a poor prognosis in two independent series accounting 279 patients. Notably, a combination treatment of a selective HDAC6 and doxorubicin (a DNA damage agent used as a standard therapy of EWS patients) dramatically inhibits tumor growth in two EWS murine xenograft models. These results could lead to suitable and promising therapeutic alternatives for patients with EWS.
NSUN2-mediated RNA 5-methylcytosine promotes esophageal squamous cell carcinoma progression via LIN28B-dependent GRB2 mRNA stabilization
Authors: Su Jiachun , Wu Guandi , Ye Ying , Zhang Jialiang , Zeng Lingxing , Huang Xudong , Zheng Yanfen , Bai Ruihong , Zhuang Lisha , Li Mei , Pan Ling , Deng Junge , Li Rui , Deng Shuang , Zhang Shaoping , Zuo Zhixiang , Liu Zexian , Lin Junzhong , Lin Dongxin , Zheng Jian
Published: August 2021

5-Methylcytosine (m5C) is a posttranscriptional RNA modification participating in many critical bioprocesses, but its functions in human cancer remain unclear. Here, by detecting the transcriptome-wide m5C profiling in esophageal squamous cell carcinoma (ESCC), we showed increased m5C methylation in ESCC tumors due to the overexpressed m5C methyltransferase NSUN2. Aberrant expression of NSUN2 was positively regulated by E2F Transcription Factor 1 (E2F1). High NSUN2 levels predicted poor survival of ESCC patients. Moreover, silencing NSUN2 suppressed ESCC tumorigenesis and progression in Nsun2 knockout mouse models. Mechanistically, NSUN2 induced m5C modification of growth factor receptor-bound protein 2 (GRB2) and stabilized its mRNA, which was mediated by a novel m5C mediator, protein lin-28 homolog B (LIN28B). Elevated GRB2 levels increased the activation of PI3K/AKT and ERK/MAPK signalling. These results demonstrate that NSUN2 enhances the initiation and progression of ESCC via m5C-LIN28B dependent stabilization of GRB2 transcript, providing a promising epitranscriptomic-targeted therapeutic strategy for ESCC.
Variants in PAX6, PITX3 and HSF4 causing autosomal dominant congenital cataracts
Authors: Berry Vanita , Ionides Alex , Pontikos Nikolas , Moore Anthony T. , Quinlan Roy A. , Michaelides Michel
Published: August 2021

Background

Lens development is orchestrated by transcription factors. Disease-causing variants in transcription factors and their developmental target genes are associated with congenital cataracts and other eye anomalies.

Methods

Using whole exome sequencing, we identified disease-causing variants in two large British families and one isolated case with autosomal dominant congenital cataract. Bioinformatics analysis confirmed these disease-causing mutations as rare or novel variants, with a moderate to damaging pathogenicity score, with testing for segregation within the families using direct Sanger sequencing.

Results

Family A had a missense variant (c.184 G>A; p.V62M) in PAX6 and affected individuals presented with nuclear cataract. Family B had a frameshift variant (c.470–477dup; p.A160R*) in PITX3 that was also associated with nuclear cataract. A recurrent missense variant in HSF4 (c.341 T>C; p.L114P) was associated with congenital cataract in a single isolated case.

Conclusions

We have therefore identified novel variants in PAX6 and PITX3 that cause autosomal dominant congenital cataract.
PSG-Audio, a scored polysomnography dataset with simultaneous audio recordings for sleep apnea studies
Authors: Korompili Georgia , Amfilochiou Anastasia , Kokkalas Lampros , Mitilineos Stelios A. , Tatlas Nicolas- Alexander , Kouvaras Marios , Kastanakis Emmanouil , Maniou Chrysoula , Potirakis Stelios M.
Published: August 2021

The sleep apnea syndrome is a chronic condition that affects the quality of life and increases the risk of severe health conditions such as cardiovascular diseases. However, the prevalence of the syndrome in the general population is considered to be heavily underestimated due to the restricted number of people seeking diagnosis, with the leading cause for this being the inconvenience of the current reference standard for apnea diagnosis: Polysomnography. To enhance patients’ awareness of the syndrome, a great endeavour is conducted in the literature. Various home-based apnea detection systems are being developed, profiting from information in a restricted set of polysomnography signals. In particular, breathing sound has been proven highly effective in detecting apneic events during sleep. The development of accurate systems requires multitudinous datasets of audio recordings and polysomnograms. In this work, we provide the first open access dataset, comprising 212 polysomnograms along with synchronized high-quality tracheal and ambient microphone recordings. We envision this dataset to be widely used for the development of home-based apnea detection techniques and frameworks.
Probing an Ixodes ricinus salivary gland yeast surface display with tick-exposed human sera to identify novel candidates for an anti-tick vaccine
Authors: Trentelman Jos J. A. , Tomás-Cortázar Julen , Knorr Sarah , Barriales Diego , Hajdusek Ondrej , Sima Radek , Ersoz Jasmin I. , Narasimhan Sukanya , Fikrig Erol , Nijhof Ard M. , Anguita Juan , Hovius Joppe W.
Published: August 2021

In Europe, Ixodes ricinus is the most important vector of human infectious diseases, most notably Lyme borreliosis and tick-borne encephalitis virus. Multiple non-natural hosts of I. ricinus have shown to develop immunity after repeated tick bites. Tick immunity has also been shown to impair B. burgdorferi transmission. Most interestingly, multiple tick bites reduced the likelihood of contracting Lyme borreliosis in humans. A vaccine that mimics tick immunity could therefore potentially prevent Lyme borreliosis in humans. A yeast surface display library (YSD) of nymphal I. ricinus salivary gland genes expressed at 24, 48 and 72 h into tick feeding was constructed and probed with antibodies from humans repeatedly bitten by ticks, identifying twelve immunoreactive tick salivary gland proteins (TSGPs). From these, three proteins were selected for vaccination studies. An exploratory vaccination study in cattle showed an anti-tick effect when all three antigens were combined. However, immunization of rabbits did not provide equivalent levels of protection. Our results show that YSD is a powerful tool to identify immunodominant antigens in humans exposed to tick bites, yet vaccination with the three selected TSGPs did not provide protection in the present form. Future efforts will focus on exploring the biological functions of these proteins, consider alternative systems for recombinant protein generation and vaccination platforms and assess the potential of the other identified immunogenic TSGPs.
Transcriptomic landscape of blood platelets in healthy donors
Authors: Supernat Anna , Popęda Marta , Pastuszak Krzysztof , Best Myron G. , Grešner Peter , Veld Sjors In ’t , Siek Bartłomiej , Bednarz-Knoll Natalia , Rondina Matthew T. , Stokowy Tomasz , Wurdinger Thomas , Jassem Jacek , Żaczek Anna J.
Published: August 2021

Blood platelet RNA-sequencing is increasingly used among the scientific community. Aberrant platelet transcriptome is common in cancer or cardiovascular disease, but reference data on platelet RNA content in healthy individuals are scarce and merit complex investigation. We sought to explore the dynamics of platelet transcriptome. Datasets from 204 healthy donors were used for the analysis of splice variants, particularly with regard to age, sex, blood storage time, unit of collection or library size. GenesB2M, PPBP, TMSB4X, ACTB, FTL, CLU, PF4, F13A1, GNAS, SPARC, PTMA, TAGLN2, OAZ1andOST4demonstrated the highest expression in the analysed cohort, remaining substantial transcription consistency.CSF3Rgene was found upregulated in males (fold change 2.10, FDR q < 0.05). Cohort dichotomisation according to the median age, showed upregulatedKSR1in the older donors (fold change 2.11, FDR q < 0.05). Unsupervised hierarchical clustering revealed two clusters which were irrespective of age, sex, storage time, collecting unit or library size. However, when donors are analysed globally (as vectors), sex, storage time, library size, the unit of blood collection as well as age impose a certain degree of between- and/or within-group variability. Healthy donor platelet transcriptome retains general consistency, with very few splice variants deviating from the landscape. Although multidimensional analysis reveals statistically significant variability between and within the analysed groups, biologically, these changes are minor and irrelevant while considering disease classification. Our work provides a reference for studies working both on healthy platelets and pathological conditions affecting platelet transcriptome.
Tracking oxidation-induced alterations in fibrin clot formation by NMR-based methods
Authors: Lau Wai-Hoe , White Nathan J. , Yeo Tsin-Wen , Gruen Russell L. , Pervushin Konstantin
Published: August 2021

Plasma fibrinogen is an important coagulation factor and susceptible to post-translational modification by oxidants. We have reported impairment of fibrin polymerization after exposure to hypochlorous acid (HOCl) and increased methionine oxidation of fibrinogen in severely injured trauma patients. Molecular dynamics suggests that methionine oxidation poses a mechanistic link between oxidative stress and coagulation through protofibril lateral aggregation by disruption of AαC domain structures. However, experimental evidence explaining how HOCl oxidation impairs fibrinogen structure and function has not been demonstrated. We utilized polymerization studies and two dimensional-nuclear magnetic resonance spectrometry (2D-NMR) to investigate the hypothesis that HOCl oxidation alters fibrinogen conformation and T2 relaxation time of water protons in the fibrin gels. We have demonstrated that both HOCl oxidation of purified fibrinogen and addition of HOCl-oxidized fibrinogen to plasma fibrinogen solution disrupted lateral aggregation of protofibrils similarly to competitive inhibition of fibrin polymerization using a recombinant AαC fragment (AαC 419–502). DOSY NMR measurement of fibrinogen protons demonstrated that the diffusion coefficient of fibrinogen increased by 17.4%, suggesting the oxidized fibrinogen was more compact and fast motion in the prefibrillar state. 2D-NMR analysis reflected that water protons existed as bulk water (T2) and intermediate water (T2i) in the control plasma fibrin. Bulk water T2 relaxation time was increased twofold and correlated positively with the level of HOCl oxidation. However, T2 relaxation of the oxidized plasma fibrin gels was dominated by intermediate water. Oxidation induced thinner fibers, in which less water is released into the bulk and water fraction in the hydration shell was increased. We have confirmed that T2 relaxation is affected by the self-assembly of fibers and stiffness of the plasma fibrin gel. We propose that water protons can serve as an NMR signature to probe oxidative rearrangement of the fibrin clot.
Macroscale patterns of oceanic zooplankton composition and size structure
Authors: Brandão Manoela C. , Benedetti Fabio , Martini Séverine , Soviadan Yawouvi Dodji , Irisson Jean-Olivier , Romagnan Jean-Baptiste , Elineau Amanda , Desnos Corinne , Jalabert Laëtitia , Freire Andrea S. , Picheral Marc , Guidi Lionel , Gorsky Gabriel , Bowler Chris , Karp-Boss Lee , Henry Nicolas , de Vargas Colomban , Sullivan Matthew B. ,   Tara Oceans Consortium Coordinators, Acinas Silvia G. , Babin Marcel , Bork Peer , Boss Emmanuel , Bowler Chris , Cochrane Guy , de Vargas Colomban , Gorsky Gabriel , Guidi Lionel , Grimsley Nigel , Hingamp Pascal , Iudicone Daniele , Jaillon Olivier , Kandels Stefanie , Karp-Boss Lee , Karsenti Eric , Not Fabrice , Ogata Hiroyuki , Poulton Nicole , Pesant Stephane , Raes Jeroen , Sardet Christian , Speich Sabrina , Stemmann Lars , Sullivan Matthew B. , Sunagawa Shinichi , Wincker Patrick , Stemmann Lars , Lombard Fabien
Published: August 2021

Ocean plankton comprise organisms from viruses to fish larvae that are fundamental to ecosystem functioning and the provision of marine services such as fisheries and CO2 sequestration. The latter services are partly governed by variations in plankton community composition and the expression of traits such as body size at community-level. While community assembly has been thoroughly studied for the smaller end of the plankton size spectrum, the larger end comprises ectotherms that are often studied at the species, or group-level, rather than as communities. The body size of marine ectotherms decreases with temperature, but controls on community-level traits remain elusive, hindering the predictability of marine services provision. Here, we leverage Tara Oceans datasets to determine how zooplankton community composition and size structure varies with latitude, temperature and productivity-related covariates in the global surface ocean. Zooplankton abundance and median size decreased towards warmer and less productive environments, as a result of changes in copepod composition. However, some clades displayed the opposite relationships, which may be ascribed to alternative feeding strategies. Given that climate models predict increasingly warmed and stratified oceans, our findings suggest that zooplankton communities will shift towards smaller organisms which might weaken their contribution to the biological carbon pump.
A new image encryption scheme based on fractional-order hyperchaotic system and multiple image fusion
Authors: Gao Xinyu , Yu Jiawu , Banerjee Santo , Yan Huizhen , Mou Jun
Published: August 2021

A multi-image encryption scheme based on the fractional-order hyperchaotic system is designed in this paper. The chaotic characteristics of this system are analyzed by the phase diagram, Lyapunov exponent and bifurcation diagram. According to the analyses results, an interesting image encryption algorithm is proposed. Multiple grayscale images are fused into a color image using different channels. Then, the color image is scrambled and diffused in order to obtain a more secure cipher image. The pixel confusion operation and diffusion operation are assisted by fractional hyperchaotic system. Experimental simulation and test results indicate that the devised multi-image encryption scheme can effectively encrypt multiple images, which increase the efficiency of image encryption and transmission, and have good security performance.
Cortical representation of experimental periodontal pain: a functional magnetic resonance imaging study
Authors: Maurer Angelika , Verma Damian , Reddehase Annika , Scheef Lukas , Radbruch Alexander , Attenberger Ulrike , Jäger Andreas , Boecker Henning
Published: August 2021

The aim of this study was to investigate central pain representations during loading of the periodontium induced by orthodontic and occlusal stress. Nineteen healthy male volunteers (25.7 ± 2.8 years) were tested on two consecutive days: after phenotyping (questionnaires) and determination of warmth (WPT) and heat (HPT) pain thresholds, functional magnetic resonance imaging was performed as event-related paradigm including 36 tooth clenchings of 3 s duration, alternating with rest periods varying between 20–30 s. The task was performed in absence (T1) and 24 h after placement of an elastic separator between the second bicuspid and the first molar on the right side of the lower jaw (T2). No significant changes in WPT and HPT were observed but pain ratings were significantly elevated at T2. Significantly elevated activation at T2, as compared to T1, was found in bilateral sensorimotor cortex, bilateral secondary sensory cortex, supplementary motor area, right rolandic operculum, and bilateral insula. Our data show for the first time in humans that periodontal stimulation, as tested by tooth clenching in the presence of an elastic separator, goes along with specific expressions of pain at behavioral and neuronal network levels. Findings supplement the existing neuroimaging literature on odontogenic pain.
The COL-4A1 polypeptide destroy endothelial cells through the TGF-β/PI3K/AKT pathway
Authors: Li Ting , Ling Zhonghui , Xie Kaipeng , Wang Yixiao , Miao Zhijing , Ji Xiaohong , Li Jingyun , Hou Wenwen , Tang Qiuqin , Yuan Xiaojie , Li Nan , Li Chanjuan , Ding Hongjuan
Published: August 2021

Preeclampsia (PE) is commonly considered as a placental disorder in pregnancy. Until now, the etiology and pathological mechanism of PE have remained ambiguous. Although PE can lead to a variety of maternal and infant complications, there are still no effective treatments. This study aimed to explore the correlation between the novel polypeptide COL-4A1 and PE, and to identify the underlying mechanism by which this polypeptide may function and to explore new therapeutic targets for PE. A rat model of PE was established and used to verify the function of the polypeptide COL-4A1 in vivo. Additionally, human umbilical vascular endothelial cells (HUVECs) were cultured with or without COL-4A1 and TNF-α (20 ng/ml). Cell Counting Kit-8 (CCK-8), wound-healing, Transwell and tube formation assays were used to evaluate cell proliferation, migration and angiopoiesis. RNA sequencing and mass spectrometry were conducted to explore the underlying downstream mechanism of COL-4A1. In vivo, COL-4A1 increased blood pressure and elevated the risk of fetal growth restriction (FGR) which was induced by lipopolysaccharide (LPS) in the rat model. In vitro, COL-4A1 significantly inhibited the proliferation and migration of HUVECs. After culture with COL-4A1, compared to control group the adhesive ability and level of reactive oxygen species (ROS) were enhanced and tube formation ability was decreased. Furthermore, Western blotting (WB) and pull-down assays were conducted to explore the underlying mechanism by which COL-4A1 functions, and the TGF-β/PI3K/AKT pathway was identified as the potential pathway involved in its effects. In summary, these results revealed that the polypeptide COL-4A1 caused PE-like symptoms in cells and a rat model. Through the TGF-β/PI3K/AKT pathway, COL-4A1 interferes with the pathogenesis of PE. Thus COL-4A1 is expected to become a potential target of PE, providing a basis for exploring the treatment of PE.
TrendyGenes, a computational pipeline for the detection of literature trends in academia and drug discovery
Authors: Serrano Nájera Guillermo , Narganes Carlón David , Crowther Daniel J.
Published: August 2021

Target identification and prioritisation are prominent first steps in modern drug discovery. Traditionally, individual scientists have used their expertise to manually interpret scientific literature and prioritise opportunities. However, increasing publication rates and the wider routine coverage of human genes by omic-scale research make it difficult to maintain meaningful overviews from which to identify promising new trends. Here we propose an automated yet flexible pipeline that identifies trends in the scientific corpus which align with the specific interests of a researcher and facilitate an initial prioritisation of opportunities. Using a procedure based on co-citation networks and machine learning, genes and diseases are first parsed from PubMed articles using a novel named entity recognition system together with publication date and supporting information. Then recurrent neural networks are trained to predict the publication dynamics of all human genes. For a user-defined therapeutic focus, genes generating more publications or citations are identified as high-interest targets. We also used topic detection routines to help understand why a gene is trendy and implement a system to propose the most prominent review articles for a potential target. This TrendyGenes pipeline detects emerging targets and pathways and provides a new way to explore the literature for individual researchers, pharmaceutical companies and funding agencies.