bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Hydraulic Geometry to High Gradient Rivers in Southern Ecuador
Authors: Carrillo V. M. , Petrie J. E. , Cisneros F. E. , Timbe L. M.
Published: February 2021

Using hydraulic geometry (HG) theory, we investigated three rivers typical of the Ecuadorian mountainous region with longitudinal slopes ranging from 0.8% to 10% and coarse bed material with d50 ranging from 3 to 54 mm and values of d90 up to 908 mm. Extensive field measurements were performed to characterize geometric and hydraulic properties at 33 sites. Using these field data, at‐a‐station HG relationships were obtained for top width, average flow depth, and average flow velocity. Dimensional and dimensionless downstream HG relations were obtained for these parameters as well as the channel bed slope using the bankfull discharge estimated with at‐a‐station HG. The correlation coefficients indicate that the dimensionless equations adequately represent the observed data for all quantities with the exception of slope. In addition to a low correlation coefficient, the exponent on non‐dimensional discharge was small in the downstream HG relation for slope. This small exponent indicates that slope is not dependent on discharge. Based on this finding, the non‐dimensional HG relations were reformulated using both dimensionless discharge and bed slope as independent variables. These new relations show improved correlation coefficients and demonstrate the role of slope in determining channel width, flow depth, and average velocity in high gradient rivers.
Performance of ICESat‐2 Precision Pointing Determination
Authors: Bae Sungkoo , Helgeson Benjamin , James Michael , Magruder Lori , Sipps Jonathan , Luthcke Scott , Thomas Taylor
Published: February 2021

Global elevations are critical to understanding the Earth's dynamic processes and changing climate. These measurements are best acquired from a space‐based vantage point and are most accurate using laser altimetry technology. However, the accuracy associated with the elevation retrievals from laser altimetry relies heavily on the ability to precisely determine the pointing angle of the laser beams from the satellite to the illuminated spot on the surface. The Ice, Cloud, and land Elevation Satellite 2 (ICESat‐2) has a system consisting of instruments that support the determination of the laser pointing direction through a process called Precision Pointing Determination (PPD). In this paper, we describe the PPD conceptual implementation, instrument details, data processing approach, calibration/validation techniques, and performance assessment. We show that the PPD has successfully achieved the allocated accuracy goal essential to meeting the ICESat‐2 geolocation mission requirement.
ICESat‐2 Precision Orbit Determination
Authors: Thomas T. C. , Luthcke S. B. , Pennington T. A. , Nicholas J. B. , Rowlands D. D.
Published: February 2021

The ICESat‐2 Precision Orbit Determination (POD) system computes the precise position of the laser altimeter instrument in inertial space, a measurement necessary for accurate geolocation of individual photon surface returns. ICESat‐2 POD solutions are generated by the reduction of Global Positioning System (GPS) double‐difference carrier phase observable residuals with NASA Goddard Space Flight Center's GEODYN software. Independent satellite laser ranging (SLR) measurements are withheld from the POD solutions and used as an independent arbiter of POD performance. Measurement model updates in the form of estimated GPS antenna phase center and satellite laser ranging retro‐reflector tracking point offset vectors as well as a GPS antenna phase center variation map have led to significant improvement in POD performance. GPS residual analysis and orbit precision analysis show no significant anomalous temporal or geographic POD performance issues. The independent SLR residual analysis indicates that POD solutions have achieved a radial orbit accuracy just below 1.5 cm, thus exceeding the mission radial orbit accuracy requirement of 3.0 cm by more than a factor of 2. Future POD processing updates have been identified and will lead to even further improvements in POD performance.
TROPOMI NO2 in the United States: A Detailed Look at the Annual Averages, Weekly Cycles, Effects of Temperature, and Correlation With Surface NO2 Concentrations
Authors: Goldberg Daniel L. , Anenberg Susan C. , Kerr Gaige Hunter , Mohegh Arash , Lu Zifeng , Streets David G.
Published: February 2021

Observing the spatial heterogeneities of NO2 air pollution is an important first step in quantifying NOX emissions and exposures. This study investigates the capabilities of the Tropospheric Monitoring Instrument (TROPOMI) in observing the spatial and temporal patterns of NO2 pollution in the continental United States. The unprecedented sensitivity of the sensor can differentiate the fine‐scale spatial heterogeneities in urban areas, such as emissions related to airport/shipping operations and high traffic, and the relatively small emission sources in rural areas, such as power plants and mining operations. We then examine NO2 columns by day‐of‐the‐week and find that Saturday and Sunday concentrations are 16% and 24% lower respectively, than during weekdays. We also analyze the correlation of daily maximum 2‐m temperatures and NO2 column amounts and find that NO2 is larger on the hottest days (>32°C) as compared to warm days (26°C–32°C), which is in contrast to a general decrease in NO2 with increasing temperature at moderate temperatures. Finally, we demonstrate that a linear regression fit of 2019 annual TROPOMI NO2 data to annual surface‐level concentrations yields relatively strong correlation (R2 = 0.66). These new developments make TROPOMI NO2 satellite data advantageous for policymakers and public health officials, who request information at high spatial resolution and short timescales, in order to assess, devise, and evaluate regulations.
Brittle Faulting of Ductile Rock Induced by Pore Fluid Pressure Build‐Up
Authors: Noël Corentin , Passelègue François X. , Violay Marie
Published: February 2021

Under upper crustal conditions, deformations are primarily brittle (i.e., localized) and accommodated by frictional mechanisms. At greater depth, deformations are ductile (i.e., distributed) and accommodated by crystal plasticity, diffusion mass transfer or cataclastic flow. The transition from the brittle to the ductile domain is not associated with a critical depth, but rather varies in time and space. One main parameter controlling the variation of this transition is the pore fluid pressure. On the one hand, a pore fluid pressure increase reduces the effective stresses and possibly increases the strain rate, bringing the system closer to brittle conditions. On the other hand, pore fluid can favor ductile mechanisms, mostly via chemical effects, by facilitating intra‐crystalline plasticity, enhancing fluid‐solid diffusion and fracture healing/sealing. We report triaxial laboratory experiments that investigated the effect of pore fluid pressure increase during the ductile deformation of Tavel limestone. Three injection rates were tested: 1, 5, and 10 MPa/min. We demonstrate that: (1) Under initially ductile conditions pore fluid pressure increase immediately turns the system from compaction to dilation. (2) Dilation is due to the development of localized shear fractures. However, the macroscopic localization of the deformation is not instantaneous when the ductile to brittle transition is surpassed; a transient creeping phase is first needed. (3) To reach macroscopic brittle failure of initially ductile samples, a critical dilatancy is required. (4) Injection rate controls the final fracture distribution. We demonstrate that pore pressure build‐up in a rock undergoing ductile deformation can induce shear fracturing of the system.
Connecting Sediment Retention to Distributary‐Channel Hydrodynamics and Sediment Dynamics in a Tide‐dominated Delta: The Ayeyarwady Delta, Myanmar
Authors: Glover H. E. , Ogston A. S. , Fricke A. T. , Nittrouer C. A. , Aung Cherry , Naing Thet , Kyu Kyu Khin , Htike Htike
Published: February 2021

The largest deltas on Earth are tide‐dominated with multiple distributaries, which can experience different forcings. Yet, most observational studies of sediment dynamics in these systems focus on a single distributary. Comparison of the tidal‐to‐estuarine reaches of three representative distributaries of the Ayeyarwady Delta, Myanmar highlights the variability in sediment retention and export within a megadelta. The Ayeyarwady River has no mainstem dams, providing an opportunity to examine a relatively natural, monsoon‐dominated system. Observations were collected during high flow (September 2017) and low flow (March 2018 and 2019). The eastern Yangon distributary empties into the sheltered Gulf of Mottoma while the central Bogale and western Pathein distributaries are exposed to seasonal waves. During high flow, suspended‐sediment concentration (SSC) was consistent across all three distributaries (0.2–0.4 g/L). The upper delta retained 20%–60% of the mainstem sediment load, while the lower distributaries were tidal rivers exporting sediment. During low flow, the lower distributaries were partially mixed estuaries with little net discharge. However, SSC increased to >1 g/L in the Yangon distributary, remained constant in the Bogale distributary, and decreased in the Pathein distributary compared to high flow. This difference was driven by offshore sediment supply; fine sediment is retained near the mouth of the Yangon and advected away from the Pathein distributary. Consequently, nearshore sediment residence time in monsoon‐influenced megadeltas is controlled by coastal orientation, the timing of discharge with respect to ocean conditions, and tidal amplification. Changes to fluvial sediment delivery can cause non‐uniform coastal impacts due to these differing distributary processes.
Building Resilience in Rural America
Authors: Jerolleman Alessandra
Published: February 2021

People in rural communities are often hit disproportionately hard by natural hazards, largely because of in-equitable and inflexible risk reduction policies. But there are ways to change that.
Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota
Authors: Wang Yan , Tong Qian , Ma Shu-Rong , Zhao Zhen-Xiong , Pan Li-Bin , Cong Lin , Han Pei , Peng Ran , Yu Hang , Lin Yuan , Gao Tian-Le , Shou Jia-Wen , Li Xiao-Yang , Zhang Xian-Feng , Zhang Zheng-Wei , Fu Jie , Wen Bao-Ying , Yu Jin-Bo , Cao Xuetao , Jiang Jian-Dong
Published: February 2021

The phenylalanine–tyrosine–dopa–dopamine pathway provides dopamine to the brain. In this process, tyrosine hydroxylase (TH) is the rate-limiting enzyme that hydroxylates tyrosine and generates levodopa (l-dopa) with tetrahydrobiopterin (BH4) as a coenzyme. Here, we show that oral berberine (BBR) might supply H• through dihydroberberine (reduced BBR produced by bacterial nitroreductase) and promote the production of BH4 from dihydrobiopterin; the increased BH4 enhances TH activity, which accelerates the production of l-dopa by the gut bacteria. Oral BBR acts in a way similar to vitamins. The l-dopa produced by the intestinal bacteria enters the brain through the circulation and is transformed to dopamine. To verify the gut–brain dialog activated by BBR’s effect, Enterococcus faecalis or Enterococcus faecium was transplanted into Parkinson’s disease (PD) mice. The bacteria significantly increased brain dopamine and ameliorated PD manifestation in mice; additionally, combination of BBR with bacteria showed better therapeutic effect than that with bacteria alone. Moreover, 2,4,6-trimethyl-pyranylium tetrafluoroborate (TMP-TFB)-derivatized matrix-assisted laser desorption mass spectrometry (MALDI-MS) imaging of dopamine identified elevated striatal dopamine levels in mouse brains with oral Enterococcus, and BBR strengthened the imaging intensity of brain dopamine. These results demonstrated that BBR was an agonist of TH in Enterococcus and could lead to the production of l-dopa in the gut. Furthermore, a study of 28 patients with hyperlipidemia confirmed that oral BBR increased blood/fecal l-dopa by the intestinal bacteria. Hence, BBR might improve the brain function by upregulating the biosynthesis of l-dopa in the gut microbiota through a vitamin-like effect.
Neuroticism alters the transcriptome of the frontal cortex to contribute to the cognitive decline and onset of Alzheimer’s disease
Authors: De Jager Céline H. , White Charles C. , Bennett David A. , Ma Yiyi
Published: February 2021

Accumulating evidence has suggested that the molecular transcriptional mechanism contributes to Alzheimer’s disease (AD) and its endophenotypes of cognitive decline and neuropathological traits, β-amyloid (Aβ) and phosphorylated tangles (TAU). However, it is unknown what is the impact of the AD risk factors, personality characteristics assessed by the NEO Five-Factor Inventory, on the human brain’s transcriptome. Using postmortem human brain samples from 466 subjects, we found that neuroticism has a significant overall impact on the brain transcriptome (omnibusP = 0.005) but not the other four personality characteristics. Focused on those cognitive decline related gene co-expressed modules, neuroticism has nominally significant associations (P < 0.05) with four neuronal modules, which are more related to PHFtau than Aβ across all eight brain regions. Furthermore, the effect of neuroticism on cognitive decline and AD might be mediated through the expression of module 7 and TAU pathology (P = 0.008). To conclude, neuroticism has a broad impact on the transcriptome of human brains, and its effect on cognitive decline and AD may be mediated through gene transcription programs related to TAU pathology.
Neuregulin signaling mediates the acute and sustained antidepressant effects of subanesthetic ketamine
Authors: Grieco Steven F. , Qiao Xin , Johnston Kevin G. , Chen Lujia , Nelson Renetta R. , Lai Cary , Holmes Todd C. , Xu Xiangmin
Published: February 2021

Subanesthetic ketamine evokes rapid antidepressant effects in human patients that persist long past ketamine’s chemical half-life of ~2 h. Ketamine’s sustained antidepressant action may be due to modulation of cortical plasticity. We find that ketamine ameliorates depression-like behavior in the forced swim test in adult mice, and this depends on parvalbumin-expressing (PV) neuron-directed neuregulin-1 (NRG1)/ErbB4 signaling. Ketamine rapidly downregulates NRG1 expression in PV inhibitory neurons in mouse medial prefrontal cortex (mPFC) following a single low-dose ketamine treatment. This NRG1 downregulation in PV neurons co-tracks with the decreases in synaptic inhibition to mPFC excitatory neurons for up to a week. This results from reduced synaptic excitation to PV neurons, and is blocked by exogenous NRG1 as well as by PV targeted ErbB4 receptor knockout. Thus, we conceptualize that ketamine’s effects are mediated through rapid and sustained cortical disinhibition via PV-specific NRG1 signaling. Our findings reveal a novel neural plasticity-based mechanism for ketamine’s acute and long-lasting antidepressant effects.
Oxidative stress-induced mitophagy is suppressed by the miR-106b-93-25 cluster in a protective manner
Authors: Zhang Cheng , Nie Pengqing , Zhou Chunliu , Hu Yue , Duan Suling , Gu Meijia , Jiang Dongxu , Wang Yunfu , Deng Zixin , Chen Jincao , Chen Shi , Wang Lianrong
Published: February 2021

Increased reactive oxygen species levels in the mitochondrial matrix can induce Parkin-dependent mitophagy, which selectively degrades dysfunctional mitochondria via the autolysosome pathway. Phosphorylated mitofusin-2 (MFN2), a receptor of parkin RBR E3 ubiquitin-protein ligase (Parkin), interacts with Parkin to promote the ubiquitination of mitochondrial proteins; meanwhile, the mitophagy receptors Optineurin (OPTN) and nuclear dot protein 52 (NDP52) are recruited to damaged mitochondria to promote mitophagy. However, previous studies have not investigated changes in the levels of OPTN, MFN2, and NDP52 during Parkin-mediated mitophagy. Here, we show that mild and sustained hydrogen peroxide (H2O2) stimulation induces Parkin-dependent mitophagy accompanied by downregulation of the mitophagy-associated proteins OPTN, NDP52, and MFN2. We further demonstrate that H2O2promotes the expression of the miR-106b-93-25 cluster and that miR-106b and miR-93 synergistically inhibit the translation of OPTN, NDP52, and MFN2 by targeting their 3’ untranslated regions. We further reveal that compromised phosphorylation of MYC proto-oncogene protein (c-Myc) at threonine 58 (T58) (producing an unstable form of c-Myc) caused by reduced nuclear glycogen synthase kinase-3 beta (GSK3β) levels contributes to the promotion of miR-106b-93-25 cluster expression upon H2O2induction. Furthermore, miR-106b-mediated and miR-93-mediated inhibition of mitophagy-associated proteins (OPTN, MFN2, and NDP52) restrains cell death by controlling excessive mitophagy. Our data suggest that microRNAs (miRNAs) targeting mitophagy-associated proteins maintain cell survival, which is a novel mechanism of mitophagy control. Thus, our findings provide mechanistic insight into how miRNA-mediated regulation alters the biological process of mitophagy.
SIV-induced terminally differentiated adaptive NK cells in lymph nodes associated with enhanced MHC-E restricted activity
Authors: Huot Nicolas , Rascle Philippe , Petitdemange Caroline , Contreras Vanessa , Stürzel Christina M. , Baquero Eduard , Harper Justin L. , Passaes Caroline , Legendre Rachel , Varet Hugo , Madec Yoann , Sauermann Ulrike , Stahl-Hennig Christiane , Nattermann Jacob , Saez-Cirion Asier , Le Grand Roger , Keith Reeves R. , Paiardini Mirko , Kirchhoff Frank , Jacquelin Beatrice , Müller-Trutwin Michaela
Published: February 2021

Natural killer (NK) cells play a critical understudied role during HIV infection in tissues. In a natural host of SIV, the African green monkey (AGM), NK cells mediate a strong control of SIVagm infection in secondary lymphoid tissues. We demonstrate that SIVagm infection induces the expansion of terminally differentiated NKG2alowNK cells in secondary lymphoid organs displaying an adaptive transcriptional profile and increased MHC-E-restricted cytotoxicity in response to SIV Env peptides while expressing little IFN-γ. Such NK cell differentiation was lacking in SIVmac-infected macaques. Adaptive NK cells displayed no increasedNKG2Cexpression. This study reveals a previously unknown profile of NK cell adaptation to a viral infection, thus accelerating strategies toward NK-cell directed therapies and viral control in tissues.
Discovery of exolytic heparinases and their catalytic mechanism and potential application
Authors: Zhang Qingdong , Cao Hai-Yan , Wei Lin , Lu Danrong , Du Min , Yuan Min , Shi Deling , Chen Xiangxue , Wang Peng , Chen Xiu-Lan , Chi Lianli , Zhang Yu-Zhong , Li Fuchuan
Published: February 2021

Heparinases (Hepases) are critical tools for the studies of highly heterogeneous heparin (HP)/heparan sulfate (HS). However, exolytic heparinases urgently needed for the sequencing of HP/HS chains remain undiscovered. Herein, a type of exolytic heparinases (exoHepases) is identified from the genomes of different bacteria. These exoHepases share almost no homology with known Hepases and prefer to digest HP rather than HS chains by sequentially releasing unsaturated disaccharides from their reducing ends. The structural study of an exoHepase (BIexoHep) shows that an N-terminal conserved DUF4962 superfamily domain is essential to the enzyme activities of these exoHepases, which is involved in the formation of a unique L-shaped catalytic cavity controlling the sequential digestion of substrates through electrostatic interactions. Further, several HP octasaccharides have been preliminarily sequenced by using BIexoHep. Overall, this study fills the research gap of exoHepases and provides urgently needed tools for the structural and functional studies of HP/HS chains.
Fibrogranular materials function as organizers to ensure the fidelity of multiciliary assembly
Authors: Zhao Huijie , Chen Qingxia , Li Fan , Cui Lihong , Xie Lele , Huang Qiongping , Liang Xin , Zhou Jun , Yan Xiumin , Zhu Xueliang
Published: February 2021

Multicilia are delicate motile machineries, and how they are accurately assembled is poorly understood. Here, we show that fibrogranular materials (FGMs), large arrays of electron-dense granules specific to multiciliated cells, are essential for their ultrastructural fidelity. Pcm1 forms the granular units that further network into widespread FGMs, which are abundant in spherical FGM cores. FGM cores selectively concentrate multiple important centriole-related proteins as clients, including Cep131 that specifically decorates a foot region of ciliary central pair (CP) microtubules. FGMs also tightly contact deuterosome-procentriole complexes. Disruption of FGMs in mouse cells undergoing multiciliogenesis by Pcm1 RNAi markedly deregulates centriolar targeting of FGM clients, elongates CP-foot, and alters deuterosome size, number, and distribution. Although the multicilia are produced in correct numbers, they display abnormal ultrastructure and motility. Our results suggest that FGMs organize deuterosomes and centriole-related proteins to facilitate the faithful assembly of basal bodies and multiciliary axonemes.
Flexible thermal interface based on self-assembled boron arsenide for high-performance thermal management
Authors: Cui Ying , Qin Zihao , Wu Huan , Li Man , Hu Yongjie
Published: February 2021

Thermal management is the most critical technology challenge for modern electronics. Recent key materials innovation focuses on developing advanced thermal interface of electronic packaging for achieving efficient heat dissipation. Here, for the first time we report a record-high performance thermal interface beyond the current state of the art, based on self-assembled manufacturing of cubic boron arsenide (s-BAs). The s-BAs exhibits highly desirable characteristics of high thermal conductivity up to 21 W/m·K and excellent elastic compliance similar to that of soft biological tissues down to 100 kPa through the rational design of BAs microcrystals in polymer composite. In addition, the s-BAs demonstrates high flexibility and preserves the high conductivity over at least 500 bending cycles, opening up new application opportunities for flexible thermal cooling. Moreover, we demonstrated device integration with power LEDs and measured a superior cooling performance of s-BAs beyond the current state of the art, by up to 45 °C reduction in the hot spot temperature. Together, this study demonstrates scalable manufacturing of a new generation of energy-efficient and flexible thermal interface that holds great promise for advanced thermal management of future integrated circuits and emerging applications such as wearable electronics and soft robotics.
Revealing the role of the human blood plasma proteome in obesity using genetic drivers
Authors: Zaghlool Shaza B. , Sharma Sapna , Molnar Megan , Matías-García Pamela R. , Elhadad Mohamed A. , Waldenberger Melanie , Peters Annette , Rathmann Wolfgang , Graumann Johannes , Gieger Christian , Grallert Harald , Suhre Karsten
Published: February 2021

Blood circulating proteins are confounded readouts of the biological processes that occur in different tissues and organs. Many proteins have been linked to complex disorders and are also under substantial genetic control. Here, we investigate the associations between over 1000 blood circulating proteins and body mass index (BMI) in three studies including over 4600 participants. We show that BMI is associated with widespread changes in the plasma proteome. We observe 152 replicated protein associations with BMI. 24 proteins also associate with a genome-wide polygenic score (GPS) for BMI. These proteins are involved in lipid metabolism and inflammatory pathways impacting clinically relevant pathways of adiposity. Mendelian randomization suggests a bi-directional causal relationship of BMI with LEPR/LEP, IGFBP1, and WFIKKN2, a protein-to-BMI relationship for AGER, DPT, and CTSA, and a BMI-to-protein relationship for another 21 proteins. Combined with animal model and tissue-specific gene expression data, our findings suggest potential therapeutic targets further elucidating the role of these proteins in obesity associated pathologies.
The tumor therapy landscape of synthetic lethality
Authors: Zhang Biyu , Tang Chen , Yao Yanli , Chen Xiaohan , Zhou Chi , Wei Zhiting , Xing Feiyang , Chen Lan , Cai Xiang , Zhang Zhiyuan , Sun Shuyang , Liu Qi
Published: February 2021

Synthetic lethality is emerging as an important cancer therapeutic paradigm, while the comprehensive selective treatment opportunities for various tumors have not yet been explored. We develop the Synthetic Lethality Knowledge Graph (SLKG), presenting the tumor therapy landscape of synthetic lethality (SL) and synthetic dosage lethality (SDL). SLKG integrates the large-scale entity of different tumors, drugs and drug targets by exploring a comprehensive set of SL and SDL pairs. The overall therapy landscape is prioritized to identify the best repurposable drug candidates and drug combinations with literature supports, in vitro pharmacologic evidence or clinical trial records. Finally, cladribine, an FDA-approved multiple sclerosis treatment drug, is selected and identified as a repurposable drug for treating melanoma with CDKN2A mutation by in vitro validation, serving as a demonstrating SLKG utility example for novel tumor therapy discovery. Collectively, SLKG forms the computational basis to uncover cancer-specific susceptibilities and therapy strategies based on the principle of synthetic lethality.
Fundamental limits of electron and nuclear spin qubit lifetimes in an isolated self-assembled quantum dot
Authors: Gillard George , Griffiths Ian M. , Ragunathan Gautham , Ulhaq Ata , McEwan Callum , Clarke Edmund , Chekhovich Evgeny A.
Published: February 2021

Combining external control with long spin lifetime and coherence is a key challenge for solid state spin qubits. Tunnel coupling with electron Fermi reservoir provides robust charge state control in semiconductor quantum dots, but results in undesired relaxation of electron and nuclear spins through mechanisms that lack complete understanding. Here, we unravel the contributions of tunnelling-assisted and phonon-assisted spin relaxation mechanisms by systematically adjusting the tunnelling coupling in a wide range, including the limit of an isolated quantum dot. These experiments reveal fundamental limits and trade-offs of quantum dot spin dynamics: while reduced tunnelling can be used to achieve electron spin qubit lifetimes exceeding 1 s, the optical spin initialisation fidelity is reduced below 80%, limited by Auger recombination. Comprehensive understanding of electron-nuclear spin relaxation attained here provides a roadmap for design of the optimal operating conditions in quantum dot spin qubits.
Identification of LINC00665-miR-let-7b-CCNA2 competing endogenous RNA network associated with prognosis of lung adenocarcinoma
Authors: Huang Yusheng , Zhong Limei , Nie Kechao , Li Lijuan , Song Shaohua , Liu Fengbin , Li Peiwu , Cao Donglin , Liu Yufeng
Published: February 2021

Prognosis of patients with lung cancer remains extremely poor; thus, we sought to unearth novel competing endogenous RNA (ceRNA) networks associated with the prognosis of lung adenocarcinoma (LUAD). Aberrant mRNAs were identified from the intersection of three Gene Expression Omnibus (GEO) datasets. A protein–protein interaction (PPI) network was constructed, and miRNAs and long noncoding RNAs (lncRNAs) upstream of mRNAs were predicted. In the present study, 402 upregulated and 638 downregulated genes in lung cancer tissues were identified. Functional analysis showed significant enrichment of cancer pathways. In these top hub genes, 10 upregulated and 7 downregulated genes had substantial prognostic values in LUAD. Thirty-seven miRNAs were predicted to target 17 key genes, and only five miRNAs exhibited prognostic correlation.
Through stepwise reverse prediction and validation from miRNA to lncRNA, four key lncRNAs were identified using expression and survival analysis. Ultimately, the co-expression analysis identified LINC00665-miR-let-7b-CCNA2 as the key ceRNA network associated with the prognosis of LUAD. We successfully constructed a novel ceRNA network wherein each component was significantly associated with the prognosis of LUAD. Hence, we propose that this network may provide key biomarkers or potential therapeutic targets for LUAD prognosis.
Development of a deep learning-based software for calculating cleansing score in small bowel capsule endoscopy
Authors: Nam Ji Hyung , Hwang Youngbae , Oh Dong Jun , Park Junseok , Kim Ki Bae , Jung Min Kyu , Lim Yun Jeong
Published: February 2021

A standardized small bowel (SB) cleansing scale is currently not available. The aim of this study was to develop an automated calculation software for SB cleansing score using deep learning. Consecutively performed capsule endoscopy cases were enrolled from three hospitals. A 5-step scoring system based on mucosal visibility was trained for deep learning in the training set. Performance of the trained software was evaluated in the validation set. Average cleansing score (1.0 to 5.0) by deep learning was compared to clinical grading (A to C) reviewed by clinicians. Cleansing scores decreased as clinical grading worsened (scores of 4.1, 3.5, and 2.9 for grades A, B, and C, respectively, P < 0.001). Adequate preparation was achieved for 91.7% of validation cases. The average cleansing score was significantly different between adequate and inadequate group (4.0 vs. 2.9, P < 0.001). ROC curve analysis revealed that a cut-off value of cleansing score at 3.25 had an AUC of 0.977. Diagnostic yields for small, hard-to-find lesions were associated with high cleansing scores (4.3 vs. 3.8, P < 0.001). We developed a novel scoring software which calculates objective, automated cleansing scores for SB preparation. The cut-off value we suggested provides a standard criterion for adequate bowel preparation as a quality indicator.
A phase I dose-finding, pharmacokinetics and genotyping study of olaparib and lurbinectedin in patients with advanced solid tumors
Authors: Poveda Andres , Oaknin Ana , Romero Ignacio , Guerrero-Zotano Angel , Fariñas-Madrid Lorena , Rodriguez-Freixinos Victor , Mallol Pedro , Lopez-Reig Raquel , Lopez-Guerrero Jose Antonio
Published: February 2021

The poly (ADP-Ribose) polymerase (PARP) inhibitor olaparib has shown antitumor activity in patients with ovarian or breast cancer with or without BRCA1/2 mutations. Lurbinectedin is an ecteinascidin that generates DNA double-strand breaks. We hypothesized that the combination of olaparib and lurbinectedin maximizes the DNA damage increasing the efficacy. A 3 + 3 dose-escalation study examined olaparib tablets with lurbinectedin every 21 days. The purpose of this phase I study is to determine the dose-limiting toxicities (DLTs) of the combination, to investigate the maximum tolerated dose (MTD), the recommended phase II dose (RP2D), efficacy, pharmacokinetics, in addition to genotyping and translational studies. In total, 20 patients with ovarian and endometrial cancers were included. The most common adverse events were asthenia, nausea, vomiting, constipation, abdominal pain, neutropenia, anemia. DLT grade 4 neutropenia was observed in two patients in dose level (DL) 5, DL4 was defined as the MTD, and the RP2D was lurbinectedin 1.5 mg/m2 + olaparib 250 mg twice a day (BID). Mutational analysis revealed a median of 2 mutations/case, 53% of patients with mutations in the homologous recombination (HR) pathway. None of the patients reached a complete or partial response; however, 60% of stable disease was achieved. In conclusion, olaparib in combination with lurbinectedin was well tolerated with a disease control rate of 60%. These results deserve further evaluation of the combination in a phase II trial.
Three-dimensional tonotopic mapping of the human cochlea based on synchrotron radiation phase-contrast imaging
Authors: Li Hao , Helpard Luke , Ekeroot Jonas , Rohani Seyed Alireza , Zhu Ning , Rask-Andersen Helge , Ladak Hanif M. , Agrawal Sumit
Published: February 2021

The human cochlea transforms sound waves into electrical signals in the acoustic nerve fibers with high acuity. This transformation occurs via vibrating anisotropic membranes (basilar and tectorial membranes) and frequency-specific hair cell receptors. Frequency-positions can be mapped within the cochlea to create a tonotopic chart which fits an almost-exponential function with lowest frequencies positioned apically and highest frequencies positioned at the cochlear base (Bekesy 1960, Greenwood 1961). To date, models of frequency positions have been based on a two-dimensional analysis with inaccurate representations of the cochlear hook region. In the present study, the first three-dimensional frequency analysis of the cochlea using dendritic mapping to obtain accurate tonotopic maps of the human basilar membrane/organ of Corti and the spiral ganglion was performed. A novel imaging technique, synchrotron radiation phase-contrast imaging, was used and a spiral ganglion frequency function was estimated by nonlinear least squares fitting a Greenwood-like function (F = A (10ax − K)) to the data. The three-dimensional tonotopic data presented herein has large implications for validating electrode position and creating customized frequency maps for cochlear implant recipients.
Quantitative phase microscopy for non-invasive live cell population monitoring
Authors: Aknoun Sherazade , Yonnet Manuel , Djabari Zied , Graslin Fanny , Taylor Mark , Pourcher Thierry , Wattellier Benoit , Pognonec Philippe
Published: February 2021

We present here a label-free development based on preexisting Quantitative Phase Imaging (QPI) that allows non-invasive live monitoring of both individual cells and cell populations. Growth, death, effect of toxic compounds are quantified under visible light with a standard inverted microscope. We show that considering the global biomass of a cell population is a more robust and accurate method to assess its growth parameters in comparison to compiling individually segmented cells. This is especially true for confluent conditions. This method expands the use of light microscopy in answering biological questions concerning live cell populations even at high density. In contrast to labeling or lysis of cells this method does not alter the cells and could be useful in high-throughput screening and toxicity studies.
Changes in the human footprint in and around Indonesia’s terrestrial national parks between 2012 and 2017
Authors: Dwiyahreni Asri A. , Fuad Habiburrachman A. H. , Muhtar Sunaryo , Soesilo T. E. Budhi , Margules Chris , Supriatna Jatna
Published: February 2021

The human footprint (HF) was developed to measure of the impact of human activities on the environment. The human footprint has been found to be closely related to the vulnerability of protected areas around the world. In Indonesia, as nature conservation is still seen as hindering economic development, it is especially important to assess the human footprint in order to comprehend the overall pressures resulting from the various human activities on Indonesia’s national parks. This study measured the change in the human footprint in and around 43 terrestrial national parks over 5 years, between 2012 and 2017. As many as 37 out of 43 NPs experienced an increase in the HF, ranging from 0.4 to 77.3%. Tanjung Puting in Kalimantan experienced the greatest increase (77.3%), while Ujung Kulon in Jawa Bali bioregion had the greatest decrease (10.5%). An increase in human population density and improved access to parks from roads, rivers and coastlines are the main drivers of increasing impacts on national parks.
Occurrences of non-linear phenomena and vocal harshness in dog whines as indicators of stress and ageing
Authors: Marx András , Lenkei Rita , Pérez Fraga Paula , Bakos Viktória , Kubinyi Enikő , Faragó Tamás
Published: February 2021

During social interactions, acoustic parameters of tetrapods’ vocalisations reflect the emotional state of the caller. Higher levels of spectral noise and the occurrence of irregularities (non-linear phenomena NLP) might be negative arousal indicators in alarm calls, although less is known about other distress vocalisations. Family dogs experience different levels of stress during separation from their owner and may vocalise extensively. Analysing their whines can provide evidence for the relationship between arousal and NLP. We recorded 167 family dogs’ separation behaviour including vocalisations, assessed their stress level based on behaviour and tested how these, their individual features, and owner reported separation-related problems (SRP) relate to their whines’ (N = 4086) spectral noise and NLP. Dogs with SRP produced NLP whines more likely. More active dogs and dogs that tried to escape produced noisier whines. Older dogs’ whines were more harmonic than younger ones’, but they also showed a higher NLP ratio. Our results show that vocal harshness and NLP are associated with arousal in contact calls, and thus might function as stress indicators. The higher occurrence of NLP in older dogs irrespective to separation stress suggests loss in precise neural control of the larynx, and hence can be a potential ageing indicator.
Development of water-soluble prodrugs of the bisdioxopiperazine topoisomerase IIβ inhibitor ICRF-193 as potential cardioprotective agents against anthracycline cardiotoxicity
Authors: Bavlovič Piskáčková Hana , Jansová Hana , Kubeš Jan , Karabanovich Galina , Váňová Nela , Kollárová-Brázdová Petra , Melnikova Iuliia , Jirkovská Anna , Lenčová-Popelová Olga , Chládek Jaroslav , Roh Jaroslav , Šimůnek Tomáš , Štěrba Martin , Štěrbová-Kovaříková Petra
Published: February 2021

The bisdioxopiperazine topoisomerase IIβ inhibitor ICRF-193 has been previously identified as a more potent analog of dexrazoxane (ICRF-187), a drug used in clinical practice against anthracycline cardiotoxicity. However, the poor aqueous solubility of ICRF-193 has precluded its further in vivo development as a cardioprotective agent. To overcome this issue, water-soluble prodrugs of ICRF-193 were prepared, their abilities to release ICRF-193 were investigated using a novel UHPLC-MS/MS assay, and their cytoprotective effects against anthracycline cardiotoxicity were tested in vitro in neonatal ventricular cardiomyocytes (NVCMs). Based on the obtained results, the bis(2-aminoacetoxymethyl)-type prodrug GK-667 was selected for advanced investigations due to its straightforward synthesis, sufficient solubility, low cytotoxicity and favorable ICRF-193 release. Upon administration of GK-667 to NVCMs, the released ICRF-193 penetrated well into the cells, reached sufficient intracellular concentrations and provided effective cytoprotection against anthracycline toxicity. The pharmacokinetics of the prodrug, ICRF-193 and its rings-opened metabolite was estimated in vivo after administration of GK-667 to rabbits. The plasma concentrations of ICRF-193 reached were found to be adequate to achieve cardioprotective effects in vivo. Hence, GK-667 was demonstrated to be a pharmaceutically acceptable prodrug of ICRF-193 and a promising drug candidate for further evaluation as a potential cardioprotectant against chronic anthracycline toxicity.
Experimentally constrained early reproduction shapes life history trajectories and behaviour
Authors: Canal David , Garcia-Gonzalez Francisco , Garamszegi László Zsolt
Published: February 2021

The trade-off between current and future reproduction is a cornerstone of life history theory, but the role of within-individual plasticity on life history decisions and its connections with overall fitness and behaviour remains largely unknown. By manipulating available resources for oviposition at the beginning of the reproductive period, we experimentally constrained individual life history trajectories to take different routes in a laboratory study system, the beetle Callosobruchus maculatus, and investigated its causal effects on fecundity, survival and behaviour. Compared to females without resource limitations, females experiencing restricted conditions for oviposition had reduced fecundity early in life but increased fecundity when resources became plentiful (relative to both the previous phase and the control group) at the expense of longevity. Constrained reproduction in early life also affected behaviour, as movement activity changed differently in the two experimental groups. Experiencing reproductive constraints has, therefore, consequences for future reproduction investments and behaviour, which may lead individuals to follow different life history strategies.
Design and optimisation of magnetically-tunable hybrid piezoelectric-triboelectric energy harvester
Authors: Ganapathy Satish Rao , Salleh Hanim , Azhar Mohammad Khairul Azwan
Published: February 2021

The demand for energy harvesting technologies has been increasing over the years that can be attributed to its significance to low power applications. One of the key problems associated with the available vibration-based harvester is the maximum peak power can only be achieved when the device frequency matches the source frequency to generate low usable power. Therefore, in this study, a magnetically-tunable hybrid piezoelectric-triboelectric energy harvester (MT-HPTEH) was designed and optimised. Four key design factors: mass placement, triboelectric surface area, extension length and magnetic stiffness were investigated and optimised. The voltage generation from piezoelectric and triboelectric mechanisms was determined individually to understand the effect of each design factor on the mechanisms. An output power of 659 µW at 180 kΩ at 44 Hz was obtained from the optimised MT-HPTEH with a theoretical–experimental discrepancy of less than 10%. The added magnetically-tunable feature enabled the harvester to work at the desired frequency range with an open circuit voltage between 7.800 and 20.314 V and a frequency range from 38 to 54 Hz. This MT-HPTEH can power at least six wireless sensor networks and can be used for low power applications such as RFID tags. Future work may include designing of energy-saving and sustainable harvester.
Association of coagulation dysfunction with cardiac injury among hospitalized patients with COVID-19
Authors: Chen Liang , Hu Wei , Guo Xiaoxiao , Zhao Ping , Tang Jia , Gu Yuwei , Huang Ninghao , Wang Chao , Cui An , Zhang Dian , Hu Linjie , Feng Yi , Hu Shengshou , Chen Mingquan , Duru Firat , Xiong Chenglong
Published: February 2021

Cardiac injury is a common complication of the coronavirus disease 2019 (COVID-19), and is associated with adverse clinical outcomes. In this study, we aimed to reveal the association of cardiac injury with coagulation dysfunction. We enrolled 181 consecutive patients who were hospitalized with COVID-19, and studied the clinical characteristics and outcome of these patients. Cardiac biomarkers high-sensitivity troponin I (hs-cTnI), myohemoglobin and creatine kinase-myocardial band (CK-MB) were assessed in all patients. The clinical outcomes were defined as hospital discharge or death. The median age of the study cohort was 55 (IQR, 46–65) years, and 102 (56.4%) were males. Forty-two of the 181 patients (23.2%) had cardiac injury. Old age, high leukocyte count, and high levels of aspartate transaminase (AST), D-dimer and serum ferritin were significantly associated with cardiac injury. Multivariate regression analysis revealed old age and elevated D-dimer levels as being strong risk predictors of in-hospital mortality. Interleukin 6 (IL6) levels were comparable in patients with or without cardiac injury. Serial observations of coagulation parameters demonstrated highly synchronous alterations of D-dimer along with progression to cardiac injury. Cardiac injury is a common complication of COVID-19 and is an independent risk factor for in-hospital mortality. Old age, high leukocyte count, and high levels of AST, D-dimer and serum ferritin are significantly associated with cardiac injury, whereas IL6 are not. Therefore, the pathogenesis of cardiac injury in COVID-19 may be primarily due to coagulation dysfunction along with microvascular injury.
Insights in genetic diversity of German and Italian grape berry moth (Eupoecilia ambiguella) populations using novel microsatellite markers
Authors: Reineke Annette , Pozzebon Alberto , Herczynski Olivia , Duso Carlo
Published: February 2021

The grape berry moth Eupoecilia ambiguella (Lepidoptera: Tortricidae) is causing significant damage to grape berries, however, little is known on population genetics of this lepidopteran pest insect, hindered so far by the lack of suitable molecular markers. Here we report on the development of ten microsatellite markers of which six were used to characterise 21 E. ambiguella populations obtained from two viticultural regions in Germany and Italy. Moths were sampled during two subsequent generations (flights) in the same vineyard as well as in vineyards surrounded by different landscape types. German and Italian populations were genetically differentiated and a significant isolation by distance was evident. No significant divergence was observed among the populations from first or second flight moths, however, inbreeding was higher in first than in second flight populations. Moreover, inbreeding was influenced by habitat composition and complexity of landscape around vineyards, being positively associated with the percentage of area covered by grapevine. Population genetics of E. ambiguella could thus be affected by the presence of alternative host plants in viticultural landscapes, which is important in the light of both insecticide resistance management and sustainable pest management.
Stable isotope turnover rates and fractionation in captive California yellowtail (Seriola dorsalis): insights for application to field studies
Authors: Madigan Daniel J. , Snodgrass Owyn E. , Hyde John R. , Dewar Heidi
Published: February 2021

Stable isotope analysis (SIA) measurements from long-term captivity studies provide required parameters for interpretation of consumer SIA data. We raised young-of-the-year (14–19 cm) California yellowtail (Seriola dorsalis) on a low δ15N and δ13C diet (pellet aquaculture feed) for 525 days, then switched to a high δ15N and δ13C diet (mackerel and squid) for 753 days. Yellowtail muscle was sequentially sampled from each individual after the diet switch (0 to 753 days) and analyzed for δ15N and δ13C, allowing for calculation of diet-tissue discrimination factors (DTDFs) from two isotopically different diets (low δ15N and δ13C: pellets; high δ15N and δ13C: fish/squid) and turnover rates of 15N and 13C. DTDFs were diet dependent: Δ15N = 5.1‰, Δ13C = 3.6‰ for pellets and Δ15N = 2.6‰, Δ13C = 1.3‰ for fish/squid. Half-life estimates from 15N and 13C turnover rates for pooled yellowtail were 181 days and 341 days, respectively, but varied considerably by individual (15N: 99–239 d; 13C: 158–899 d). Quantifying DTDFs supports isotopic approaches to field data that assume isotopic steady-state conditions (e.g., mixing models for diet reconstruction). Characterizing and quantifying turnover rates allow for estimates of diet/habitat shifts and “isotopic clock” approaches, and observed inter-individual variability suggests the need for large datasets in field studies. We provide diet-dependent DTDFs and growth effects on turnover rates, and associated error around these parameters, for application to field-collected SIA data from other large teleosts.