bluuebunny/crossref_metadata_2025 huggingface dataset:
Reference Models for Lithospheric Geoneutrino Signal
Authors: Wipperfurth S. A. , Šrámek O. , McDonough W. F.
Published: January 2020

Debate continues on the amount and distribution of radioactive heat producing elements (i.e., U, Th, and K) in the Earth, with estimates for mantle heat production varying by an order of magnitude. Constraints on the bulk‐silicate Earth's (BSE) radiogenic power also places constraints on overall BSE composition. Geoneutrino detection is a direct measure of the Earth's decay rate of Th and U. The geoneutrino signal has contributions from the local (
40%) and global (
35%) continental lithosphere and the underlying inaccessible mantle (
25%). Geophysical models are combined with geochemical data sets to predict the geoneutrino signal at current and future geoneutrino detectors. We propagated uncertainties, both chemical and physical, through Monte Carlo methods. Estimated total signal uncertainties are on the order of
20%, proportionally with geophysical and geochemical inputs contributing
30% and
70%, respectively. We find that estimated signals, calculated using CRUST2.0, CRUST1.0, and LITHO1.0, are within physical uncertainty of each other, suggesting that the choice of underlying geophysical model will not change results significantly, but will shift the central value by up to
15%. Similarly, we see no significant difference between calculated layer abundances and bulk crustal heat production when using these geophysical models. The bulk crustal heat production is calculated as 7 
 2 TW, which includes an increase of 1 TW in uncertainty relative to previous studies. Combination of our predicted lithospheric signal with measured signals yield an estimated BSE heat production of 21.5 
 10.4 TW. Future improvements, including uncertainty attribution and near‐field modeling, are discussed.
Tectonic and Anthropogenic Microseismic Activity While Drilling Toward Supercritical Conditions in the Larderello‐Travale Geothermal Field, Italy
Authors: Minetto Riccardo , Montanari Domenico , Planès Thomas , Bonini Marco , Del Ventisette Chiara , Antunes Verónica , Lupi Matteo
Published: January 2020

This study investigates the seismic activity occurring at the Larderello‐Travale geothermal field, central Italy, from June 2017 to January 2018. We deployed a network composed of nine broadband stations around the Venelle 2 well drilling for supercritical fluids. During the experiment, we recognize two types of seismic events (type 1 and type 2). Type‐1 events have clear
and
wave arrivals and occur in clusters both above and below the K‐horizon, which is a seismic reflector marking a debated transition zone at depth. The distribution and evolution of the seismic sequences suggest that the K‐horizon could be interpreted as a fluid‐rich region at near‐lithostatic pressures. Type‐2 events usually occur in swarms and show a periodic pattern, a narrow frequency band, and almost identical waveforms. Their source is estimated to be located near the well, and their occurrence ceases after about 3 weeks from the conclusion of the drilling. We propose a causal link with the drilling operations where pressure fronts inside the well may promote phase changes and fluid flow across the drilled formations. Our study sheds light on the fluid‐driven tectonic and anthropogenic seismic activity at the Larderello‐Travale geothermal field. More generally, we show that microseismic activity occurring during drilling in high‐pressure and high‐temperature conditions can remain at low magnitudes and that geothermal wells targeting geothermal fluids in such systems may be handled safely despite the critical conditions encountered at depth. The drilling of the Venelle 2 well is an encouraging example for the development of geothermal energy in critical conditions.
The Atlantic Meridional Overturning Circulation in High‐Resolution Models
Authors: Hirschi Joël J.‐M. , Barnier Bernard , Böning Claus , Biastoch Arne , Blaker Adam T. , Coward Andrew , Danilov Sergey , Drijfhout Sybren , Getzlaff Klaus , Griffies Stephen M. , Hasumi Hiroyasu , Hewitt Helene , Iovino Doroteaciro , Kawasaki Takao , Kiss Andrew E. , Koldunov Nikolay , Marzocchi Alice , Mecking Jennifer V. , Moat Ben , Molines Jean‐Marc , Myers Paul G. , Penduff Thierry , Roberts Malcolm , Treguier Anne‐Marie , Sein Dmitry V. , Sidorenko Dmitry , Small Justin , Spence Paul , Thompson LuAnne , Weijer Wilbert , Xu Xiaobiao
Published: January 2020

The Atlantic meridional overturning circulation (AMOC) represents the zonally integrated stream function of meridional volume transport in the Atlantic Basin. The AMOC plays an important role in transporting heat meridionally in the climate system. Observations suggest a heat transport by the AMOC of 1.3 PW at 26°N—a latitude which is close to where the Atlantic northward heat transport is thought to reach its maximum. This shapes the climate of the North Atlantic region as we know it today. In recent years there has been significant progress both in our ability to observe the AMOC in nature and to simulate it in numerical models. Most previous modeling investigations of the AMOC and its impact on climate have relied on models with horizontal resolution that does not resolve ocean mesoscale eddies and the dynamics of the Gulf Stream/North Atlantic Current system. As a result of recent increases in computing power, models are now being run that are able to represent mesoscale ocean dynamics and the circulation features that rely on them. The aim of this review is to describe new insights into the AMOC provided by high‐resolution models. Furthermore, we will describe how high‐resolution model simulations can help resolve outstanding challenges in our understanding of the AMOC.
On the Transition From Initial Leader to Stepped Leader in Negative Cloud‐to‐Ground Lightning
Authors: Stolzenburg Maribeth , Marshall Thomas C. , Karunarathne Sumedhe
Published: January 2020

High‐speed video and electric field change data are used to describe the first 5 ms of a negative cloud‐to‐ground flash. These observations reveal an evolution in character of the luminosity and electric field change pulses as two branches of the leader separately transition from initial leader to propagating as a negative stepped leader (SL). For the first time reported, there is evidence of weak luminosity coincident with the initiating event, a weak bipolar pulse 60 μs prior to the first initial breakdown (IB) pulse. During the IB stage, the initial leader advances intermittently at intervals of 100–280 μs, in separate light bursts that are bright for a few 20‐μs frames and are time coincident with IB pulses. In the intervals between IB pulses, the initial leader is dim or invisible during the earliest 1.8 ms. Within 2 ms, the leader propagation begins transitioning to an early SL phase, in which the leader tip advances at more regular intervals of 40–80 μs during relatively dim and brief steps which are coincident with SL pulses having short duration, small amplitude, and typically unipolar waveform. These data indicate that when the entire initial leader length behind the lower end begins to remain illuminated between bursts, the propagation mode changes from IB bursts to SL steps, and the IB stage ends. The results support a hypothesis that the early initial leader development occurs in the absence of a continuously hot channel, thus the initial leader propagation is physically unlike the self‐propagating SL advance.
Wildfire‐Smoke Aerosols Lead to Increased Light Use Efficiency Among Agricultural and Restored Wetland Land Uses in California's Central Valley
Authors: Hemes Kyle S. , Verfaillie Joseph , Baldocchi Dennis D.
Published: January 2020

There are few observational studies measuring the ecosystem‐scale productivity effects of changes in incident diffuse photosynthetically active radiation (PARdiffuse), especially related to wildfire smoke. Climate change‐induced increases to the duration and intensity of fire conditions have made smoke a common occurrence across western North America, with largely unquantified ecosystem feedbacks. Under equivalent amounts of radiation, increased atmospheric particulate matter could lead to a boost in productivity as scattering redistributes photons throughout multilayer canopies. In this work, we leverage a meso‐network of eddy covariance measurement sites across a unique array of managed and restored C3 and C4 canopy types to understand how recent wildfire smoke affected ecosystem productivity during the summer of 2018, an especially smoky year in the agriculturally productive Central Valley. We find that diffuse PARdiffuse increased by more than a third compared to the previous growing season, while total PAR was only slightly diminished. These conditions caused nearly a doubling of light use efficiency over the range of diffuse fraction observed, with the highest sensitivity to diffuse fraction exhibited by corn and alfalfa crops. We utilized an empirical model to assess the trade‐off between enhanced diffuse fraction and reduced total PAR. Under mean radiation conditions, daily integrated gross ecosystem productivity increased by 1.2–4.2% compared to the previous growing season. Finally, we explore the potential negative effect of heightened ozone, a copollutant often associated with wildfire. In addition to the effects of wildfire smoke, the results of this natural experiment can help validate future predictions of aerosol‐productivity feedbacks.
Utilization and Emergency Department Diversion as a Result of Pediatric Psychology Trainees Integrated in Pediatric Primary and Specialty Clinics
Authors: Pereira Lila M. , Wallace Jenna , Brown Whitney , Stancin Terry
Published: January 2020

Purpose: Integrating behavioral health into primary care (PC) is known to be an effective approach to caring for children with complex health care needs. The purpose of this study was to describe the impact of embedding predoctoral psychology interns (PSY residents) in a continuity care clinic on behavioral health care utilization with additional attention paid to diverting emergency department (ED) visits. Method: Doctoral psychology PSY residents participated as team members in pediatric resident continuity care clinics and also were available to consult with specialty and urgent care clinic providers within the ambulatory center. During a 6-month period, services provided by PSY residents were tracked (numbers of warm-handoffs, behavioral consults [including covisits with pediatric residents], psychotherapy appointments, and crisis evaluations). Results: PSY residents completed 184 warm-handoffs, 250 same-day consults, and 223 follow-up appointments. Sixty-five patients attended group therapy sessions offered in the pediatric clinic. Of 23 patients evaluated for suicidal/homicidal ideation (who previously would have been referred immediately to the ED), 21 were stabilized in PC and only 2 required ED services. Conclusion: Integration of PSY trainees resulted in more than 700 rapid behavioral health services in 6 months, and diverted 91% of mental health crises from ED and other possible psychiatric hospitalization. Prior to integration, none of these services were provided on site. In addition to providing interprofessional team training, integrated continuity care clinics can improve access to behavioral health services and offer significant cost-saving opportunities to health care systems. Ways to promote interdisciplinary training will be identified.

Implications for Impact Statement

Embedding predoctoral psychology interns in a pediatric continuity care clinic can result in increased access to behavioral health clinicians and division of emergency department visits for high-risk patients. This model also increases opportunities for interdisciplinary training.
Degradation and modification of cochlear gap junction proteins in the early development of age-related hearing loss
Authors: Tajima Shori , Danzaki Keiko , Ikeda Katsuhisa , Kamiya Kazusaku
Published: January 2020

Age-related hearing loss (ARHL) is the progressive, bilateral loss of high-frequency hearing in elderly people. Mutations in GJB2, encoding the cochlear gap junction protein connexin26 (Cx26), are the most frequent cause of hereditary deafness; however, a common molecular pathology between ARHL and GJB2-related hearing loss has not been reported. Here, we investigated the quantitative change in expression and molecular pathology of Cx26 in ARHL. We used C57BL/6J mice as a model of ARHL. Hearing levels that were evaluated by auditory brainstem response thresholds increased gradually between 4 and 32 weeks of age and increased sharply at 36 weeks. Gap junctions in the cochleae of 4-week-old mice had linear plaques along cell–cell junction sites. In contrast, the cochleae from 32-week-old mice had significantly shorter gap junctions. Severe hair cell loss was not observed during this period. Based on western blotting, Cx26 and connexin30 (Cx30) levels were significantly decreased at 32 weeks compared with 4 weeks.

Moreover, Cx26 was more significantly enriched in the hydrophilic fraction at 4 weeks but was more significantly enriched in the hydrophobic fraction at 32 weeks, indicating an age-related conversion of this biochemical property. Thus, the hydrophobic conversion of Cx26 and disruption of gap junction proteins and plaques may be involved in the pathogenesis of ARHL and may occur before severe hair cell degeneration.
Polycomb-mediated repression of EphrinA5 promotes growth and invasion of glioblastoma
Authors: Ricci Barbara , Millner Thomas O. , Pomella Nicola , Zhang Xinyu , Guglielmi Loredana , Badodi Sara , Ceric Dario , Gemma Carolina , Cognolato Erica , Zhang Ying , Brandner Sebastian , Barnes Michael R. , Marino Silvia
Published: January 2020

Glioblastoma (GBM) is the most common and most aggressive intrinsic brain tumour in adults. Integrated transcriptomic and epigenomic analyses of glioblastoma initiating cells (GIC) in a mouse model uncovered a novel epigenetic regulation of EfnA5. In this model, Bmi1 enhances H3K27me3 at theEfnA5locus and reinforces repression of selected target genes in a cellular context-dependent fashion. EfnA5 mediates Bmi1-dependent proliferation and invasion in vitro and tumour formation in an allograft model. Importantly, we show that this novel Polycomb feed-forward loop is also active in human GIC and we provide pre-clinical evidence of druggability of the EFNA5 signalling pathway in GBM xenografts overexpressing Bmi1.
Diversity and metabolism of Woeseiales bacteria, global members of marine sediment communities
Authors: Hoffmann Katy , Bienhold Christina , Buttigieg Pier Luigi , Knittel Katrin , Laso-Pérez Rafael , Rapp Josephine Z , Boetius Antje , Offre Pierre
Published: January 2020

Surveys of 16S rRNA gene sequences derived from marine sediments have indicated that a widely distributed group of Gammaproteobacteria, named “JTB255-Marine Benthic Group” (now the candidate order Woeseiales), accounts for 1–22% of the retrieved sequences. Despite their ubiquity in seafloor communities, little is known about their distribution and specific ecological niches in the deep sea, which constitutes the largest biome globally. Here, we characterized the phylogeny, environmental distribution patterns, abundance, and metabolic potential of Woeseiales bacteria with a focus on representatives from the deep sea. From a phylogenetic analysis of publicly available 16S rRNA gene sequences (≥1400 bp, n = 994), we identified lineages of Woeseiales with greater prevalence in the deep sea than in coastal environments, a pattern corroborated by the distribution of 16S oligotypes recovered from 28 globally distributed sediment samples. Cell counts revealed that Woeseiales bacteria accounted for 5 ± 2% of all microbial cells in deep-sea surface sediments at 23 globally distributed sites. Comparative analyses of a genome, metagenome bins, and single-cell genomes suggested that members of the corresponding clades are likely to grow on proteinaceous matter, potentially derived from detrital cell membranes, cell walls, and other organic remnants in marine sediments.
LncRNA AC093818.1 accelerates gastric cancer metastasis by epigenetically promoting PDK1 expression
Authors: Ba Ming-chen , Ba Zheng , Long Hui , Cui Shu-zhong , Gong Yuan-feng , Yan Zhao-fei , Lin Kun-peng , Wu Yin-bing , Tu Yi-nuo
Published: January 2020

Gastric cancer (GC) is a highly prevalent type of metastatic tumor. The mechanisms underlying GC metastasis are poorly understood. Some long noncoding RNAs (lncRNAs) reportedly play key roles in regulating metastasis of GC. However, the biological roles of five natural antisense lncRNAs (AC093818.1, CTD-2541M15.1, BC047644, RP11-597M12.1, and RP11-40A13.1) in GC metastasis remain unclear. In this study, the expression of these lncRNAs was measured by quantitative reverse transcription-polymerase chain reaction. Migration and invasion were evaluated by wound-healing and the Transwell assay, respectively. Stable cells were injected into the tail veins of nude mice. Sections of collected lung and liver tissues were stained using hematoxylin and eosin. Protein expression was analyzed by western blot. RNA immunoprecipitation (RIP) assay was used to verify whether the STAT3 and SP1 transcription factors bound to AC093818.1 in GC cells. Expression levels of the five lncRNAs, especially AC093818.1, were significantly upregulated in metastatic GC tissues relative to those in nonmetastatic GC tissues. AC093818.1 expression was correlated with invasion, lymphatic metastasis, distal metastasis, and tumor-node-metastasis stage. AC093818.1 expression was highly sensitive and specific in the diagnosis of metastatic or nonmetastatic GC. AC093818.1 overexpression promoted GC migration and invasion in vitro and in vivo. AC093818.1 overexpression increased PDK1, p-AKT1, and p-mTOR expression levels. AC093818.1 silencing decreased these expressions. AC093818.1 bound to transcription factors STAT3 and SP1, and SP1 or STAT3 silencing could alleviated the effect of AC093818.1 overexpression. The data demonstrate that lncRNA AC093818.1 accelerates gastric cancer metastasis by epigenetically promoting PDK1 expression. LncRNA AC093818.1 may be a potential therapeutic target for metastatic GC.
Lipid desaturation-associated endoplasmic reticulum stress regulates MYCN gene expression in hepatocellular carcinoma cells
Authors: Qin Xian-Yang , Su Ting , Yu Wenkui , Kojima Soichi
Published: January 2020

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide due to its high rate of recurrence, in part because of cancer stem cell (CSC)-dependent “field cancerization”. Recently, we identified that the oncogene v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) marked CSC-like subpopulations in heterogeneous HCC and served as a therapeutic target and prognostic marker for HCC. In this study, we explored the molecular basis of upregulated MYCN gene expression in HCC cells. Liquid chromatograph time-of-flight mass spectrometry-based metabolome analysis demonstrated that the content of unsaturated fatty acids was increased in MYCN high expression (MYCNhigh) CSC-like HCC cells. Inhibition of lipid desaturation using either the chemical inhibitor or siRNA/shRNA against stearoyl-CoA desaturase-1 (SCD1) suppressed cell proliferation as well as MYCN gene expression in MYCNhigh HCC cells, grown as both monolayer and spheres. Further mechanistic study using RNA-seq based transcriptome analysis revealed that endoplasmic reticulum (ER) stress related signaling networks such as endocannabinoid cancer inhibition pathway were under the control of SCD1 in MYCNhigh HCC cells. Furthermore, the expression of ER stress-inducible transcription suppressor cyclic AMP-dependent transcription factor (ATF3) was downregulated in MYCNhigh CSC-like HCC cells and CSC-rich spheroids, which was upregulated by inhibition of lipid desaturation or treatment with acyclic retinoid (ACR). Lipid profiling using NMR spectroscopy revealed that the ACR dramatically reduced the content of unsaturated fatty acids in HCC cells. The chemical inducer of ER stress inhibited MYCN gene expression, while the chemical inhibitor of ER stress or knockdown of ATF3 gene expression partially rescued the suppression of MYCN gene expression by ACR in MYCNhigh HCC cells. These data suggested that lipid desaturation-mediated ER stress signaling regulates MYCN gene expression in HCC cells and serves as a promising therapeutic target for the treatment and prevention of HCC.
Human BCL-G regulates secretion of inflammatory chemokines but is dispensable for induction of apoptosis by IFN-γ and TNF-α in intestinal epithelial cells
Authors: Woznicki Jerzy A. , Flood Peter , Bustamante-Garrido Milan , Stamou Panagiota , Moloney Gerry , Fanning Aine , Zulquernain Syed Akbar , McCarthy Jane , Shanahan Fergus , Melgar Silvia , Nally Ken
Published: January 2020

Proteins of the BCL-2 family are evolutionarily conserved modulators of apoptosis that function as sensors of cellular integrity. Over the past three decades multiple BCL-2 family members have been identified, many of which are now fully incorporated into regulatory networks governing the mitochondrial apoptotic pathway. For some, however, an exact role in cell death signalling remains unclear. One such ‘orphan’ BCL-2 family member is BCL-G (or BCL2L14). In this study we analysed gastrointestinal expression of humanBCL-Gin health and disease states, and investigated its contribution to inflammation-induced tissue damage by exposing intestinal epithelial cells (IEC) to IFN-γ and TNF-α, two pro-inflammatory mediators associated with gut immunopathology. We found that both BCL-G splice variants — BCL-GS(short) and BCL-GL(long) — were highly expressed in healthy gut tissue, and that their mRNA levels decreased in active inflammatory bowel diseases (for BCL-GS) and colorectal cancer (for BCL-GS/L). In vitro studies revealed that IFN-γ and TNF-α synergised to upregulate BCL-GS/Land to trigger apoptosis in colonic epithelial cell lines and primary human colonic organoids. Using RNAi, we showed that synergistic induction of IEC death was STAT1-dependent while optimal expression of BCL-GS/Lrequired STAT1, NF-κB/p65 and SWI/SNF-associated chromatin remodellers BRM and BRG1. To test the direct contribution of BCL-G to the effects of IFN-γ and TNF-α on epithelial cells, we used RNAi- and CRISPR/Cas9-based perturbations in parallel with isoform-specific overexpression of BCL-G, and found that BCL-G was dispensable for Th1 cytokine-induced apoptosis of human IEC. Instead, we discovered that depletion of BCL-G differentially affected secretion of inflammatory chemokines CCL5 and CCL20, thus uncovering a non-apoptotic immunoregulatory function of this BCL-2 family member. Taken together, our data indicate that BCL-G may be involved in shaping immune responses in the human gut in health and disease states through regulation of chemokine secretion rather than intestinal apoptosis.
SETD2 mutation in renal clear cell carcinoma suppress autophagy via regulation of ATG12
Authors: González-Rodríguez Patricia , Engskog-Vlachos Pinelopi , Zhang Hanzhao , Murgoci Adriana-Natalia , Zerdes Ioannis , Joseph Bertrand
Published: January 2020

Inactivating mutations in the SETD2 gene, encoding for a nonredundant histone H3 methyltransferase and regulator of transcription, is a frequent molecular feature in clear cell renal cell carcinomas (ccRCC). SETD2 deficiency is associated with recurrence of ccRCC and bears low prognostic values. Targeting autophagy, a conserved catabolic process with critical functions in maintenance of cellular homeostasis and cell conservation under stress condition, is emerging as a potential therapeutic strategy to combat ccRCC. Epigenetics-based pathways are now appreciated as key components in the regulation of autophagy. However, whether loss of function in the SETD2 histone modifying enzyme occurring in ccRCC cells may impact on their ability to undergo autophagy remained to be explored. Here, we report that SETD2 deficiency in RCC cells is associated with the aberrant accumulation of both free ATG12 and of an additional ATG12-containing complex, distinct from the ATG5–ATG12 complex. Rescue of SETD2 functions in the SETD2 deficiency in RCC cells, or reduction of SETD2 expression level in RCC cells wild type for this enzyme, demonstrates that SETD2 deficiency in RCC is directly involved in the acquisition of these alterations in the autophagic process. Furthermore, we revealed that deficiency in SETD2, known regulator of alternative splicing, is associated with increased expression of a short ATG12 spliced isoform at the depend of the canonical long ATG12 isoform in RCC cells. The defect in the ATG12-dependent conjugation system was found to be associated with a decrease autophagic flux, in accord with the role for this ubiquitin-like protein conjugation system in autophagosome formation and expansion. Finally, we report that SETD2 and ATG12 gene expression levels are associated with favorable respective unfavorable prognosis in ccRCC patients. Collectively, our findings bring further argument for considering the SETD2 gene status of ccRCC tumors, when therapeutic interventions, such as targeting the autophagic process, are considered to combat these kidney cancers.
“Dysfunctions” induced by Roux-en-Y gastric bypass surgery are concomitant with metabolic improvement independent of weight loss
Authors: Li Meiyi , Liu Zhiyuan , Qian Bangguo , Liu Weixin , Horimoto Katsuhisa , Xia Jie , Shi Meilong , Wang Bing , Zhou Huarong , Chen Luonan
Published: January 2020

Metabolic surgery has been increasingly recommended for obese diabetic patients, but questions remain as to its molecular mechanism that leads to improved metabolic parameters independently of weight loss from a network viewpoint. We evaluated the role of the Roux limb (RL) in Roux-en-Y gastric bypass (RYGB) surgery in nonobese diabetic rat models. Improvements in metabolic parameters were greater in the long-RL RYGB group. Transcriptome profiles reveal that amelioration of diabetes state following RYGB differs remarkably from both normal and diabetic states. According to functional analysis, RYGB surgery significantly affected a major gene group, i.e., the newly changed group, which represented diabetes-irrelevant genes abnormally expressed after RYGB. We hypothesize that novel “dysfunctions” carried by this newly changed gene group induced by RYGB rebalance diabetic states and contribute to amelioration of metabolic parameters. An unusual increase in cholesterol (CHOL) biosynthesis in RL enriched by the newly changed group was concomitant with ameliorated metabolic parameters, as demonstrated by measurements of physiological parameters and biodistribution analysis using [14C]-labeled glucose. Our findings demonstrate RYGB-induced “dysfunctions” in the newly changed group as a compensatory role contributes to amelioration of diabetes. Rather than attempting to normalize “abnormal” molecules, we suggest a new disease treatment strategy of turning “normal” molecules “abnormal” in order to achieve a new “normal” physiological balance. It further implies a novel strategy for drug discovery, i.e. targeting also on “normal” molecules, which are traditionally ignored in pharmaceutical development.
Highly durable crack sensor integrated with silicone rubber cantilever for measuring cardiac contractility
Authors: Kim Dong-Su , Choi Yong Whan , Shanmugasundaram Arunkumar , Jeong Yun-Jin , Park Jongsung , Oyunbaatar Nomin-Erdene , Kim Eung-Sam , Choi Mansoo , Lee Dong-Weon
Published: January 2020

To date, numerous biosensing platforms have been developed for assessing drug-induced cardiac toxicity by measuring the change in contractile force of cardiomyocytes. However, these low sensitivity, low-throughput, and time-consuming processes are severely limited in their real-time applications. Here, we propose a cantilever device integrated with a polydimethylsiloxane (PDMS)-encapsulated crack sensor to measure cardiac contractility. The crack sensor is chemically bonded to a PDMS thin layer that allows it to be operated very stably in culture media. The reliability of the proposed crack sensor has been improved dramatically compared to no encapsulation layer. The highly sensitive crack sensor continuously measures the cardiac contractility without changing its gauge factor for up to 26 days (>5 million heartbeats), while changes in contractile force induced by drugs are monitored using the crack sensor-integrated cantilever. Finally, experimental results are compared with those obtained via conventional optical methods to verify the feasibility of building a contraction-based drug-toxicity testing system.
Geometric cues stabilise long-axis polarisation of PAR protein patterns in C. elegans
Authors: Geßele Raphaela , Halatek Jacob , Würthner Laeschkir , Frey Erwin
Published: January 2020

In the Caenorhabditis elegans zygote, PAR protein patterns, driven by mutual anatagonism, determine the anterior-posterior axis and facilitate the redistribution of proteins for the first cell division. Yet, the factors that determine the selection of the polarity axis remain unclear. We present a reaction-diffusion model in realistic cell geometry, based on biomolecular reactions and accounting for the coupling between membrane and cytosolic dynamics. We find that the kinetics of the phosphorylation-dephosphorylation cycle of PARs and the diffusive protein fluxes from the cytosol towards the membrane are crucial for the robust selection of the anterior-posterior axis for polarisation. The local ratio of membrane surface to cytosolic volume is the main geometric cue that initiates pattern formation, while the choice of the long-axis for polarisation is largely determined by the length of the aPAR-pPAR interface, and mediated by processes that minimise the diffusive fluxes of PAR proteins between cytosol and membrane.
Topological ultranodal pair states in iron-based superconductors
Authors: Setty Chandan , Bhattacharyya Shinibali , Cao Yifu , Kreisel Andreas , Hirschfeld P. J.
Published: January 2020

Bogoliubov Fermi surfaces are contours of zero-energy excitations that are protected in the superconducting state. Here we show that multiband superconductors with dominant spin singlet, intraband pairing of spin-1/2 electrons can undergo a transition to a state with Bogoliubov Fermi surfaces if spin-orbit coupling, interband pairing and time reversal symmetry breaking are also present. These latter effects may be small, but drive the transition to the topological state for appropriate nodal structure of the intra-band pair. Such a state should display nonzero zero-bias density of states and corresponding residual Sommerfeld coefficient as for a disordered nodal superconductor, but occurring even in the pure case. We present a model appropriate for iron-based superconductors where the topological transition associated with creation of a Bogoliubov Fermi surface can be studied. The model gives results that strongly resemble experiments on FeSe1−xSx across the nematic transition, where this ultranodal behavior may already have been observed.
Highly efficient three-dimensional solar evaporator for high salinity desalination by localized crystallization
Authors: Wu Lei , Dong Zhichao , Cai Zheren , Ganapathy Turga , Fang Niocholas X. , Li Chuxin , Yu Cunlong , Zhang Yu , Song Yanlin
Published: January 2020

Solar-driven water evaporation represents an environmentally benign method of water purification/desalination. However, the efficiency is limited by increased salt concentration and accumulation. Here, we propose an energy reutilizing strategy based on a bio-mimetic 3D structure. The spontaneously formed water film, with thickness inhomogeneity and temperature gradient, fully utilizes the input energy through Marangoni effect and results in localized salt crystallization. Solar-driven water evaporation rate of 2.63 kg m−2 h−1, with energy efficiency of >96% under one sun illumination and under high salinity (25 wt% NaCl), and water collecting rate of 1.72 kg m−2 h−1 are achieved in purifying natural seawater in a closed system. The crystalized salt freely stands on the 3D evaporator and can be easily removed. Additionally, energy efficiency and water evaporation are not influenced by salt accumulation thanks to an expanded water film inside the salt, indicating the potential for sustainable and practical applications.
Soil structure is an important omission in Earth System Models
Authors: Fatichi Simone , Or Dani , Walko Robert , Vereecken Harry , Young Michael H. , Ghezzehei Teamrat A. , Hengl Tomislav , Kollet Stefan , Agam Nurit , Avissar Roni
Published: January 2020

Most soil hydraulic information used in Earth System Models (ESMs) is derived from pedo-transfer functions that use easy-to-measure soil attributes to estimate hydraulic parameters. This parameterization relies heavily on soil texture, but overlooks the critical role of soil structure originated by soil biophysical activity. Soil structure omission is pervasive also in sampling and measurement methods used to train pedotransfer functions. Here we show how systematic inclusion of salient soil structural features of biophysical origin affect local and global hydrologic and climatic responses. Locally, including soil structure in models significantly alters infiltration-runoff partitioning and recharge in wet and vegetated regions. Globally, the coarse spatial resolution of ESMs and their inability to simulate intense and short rainfall events mask effects of soil structure on surface fluxes and climate. Results suggest that although soil structure affects local hydrologic response, its implications on global-scale climate remains elusive in current ESMs.
Photosynthesis-inspired H2 generation using a chlorophyll-loaded liposomal nanoplatform to detect and scavenge excess ROS
Authors: Wan Wei-Lin , Tian Bo , Lin Yu-Jung , Korupalli Chiranjeevi , Lu Ming-Yen , Cui Qinghua , Wan Dehui , Chang Yen , Sung Hsing-Wen
Published: January 2020

A disturbance of reactive oxygen species (ROS) homeostasis may cause the pathogenesis of many diseases. Inspired by natural photosynthesis, this work proposes a photo-driven H2-evolving liposomal nanoplatform (Lip NP) that comprises an upconversion nanoparticle (UCNP) that is conjugated with gold nanoparticles (AuNPs) via a ROS-responsive linker, which is encapsulated inside the liposomal system in which the lipid bilayer embeds chlorophyll a (Chla). The UCNP functions as a transducer, converting NIR light into upconversion luminescence for simultaneous imaging and therapy in situ. Functioning as light-harvesting antennas, AuNPs are used to detect the local concentration of ROS for FRET biosensing, while the Chla activates the photosynthesis of H2 gas to scavenge local excess ROS. The results thus obtained indicate the potential of using the Lip NPs in the analysis of biological tissues, restoring their ROS homeostasis, possibly preventing the initiation and progression of diseases.
Earthquake slip surfaces identified by biomarker thermal maturity within the 2011 Tohoku-Oki earthquake fault zone
Authors: Rabinowitz Hannah S. , Savage Heather M. , Polissar Pratigya J. , Rowe Christie D. , Kirkpatrick James D.
Published: January 2020

Extreme slip at shallow depths on subduction zone faults is a primary contributor to tsunami generation by earthquakes. Improving earthquake and tsunami risk assessment requires understanding the material and structural conditions that favor earthquake propagation to the trench. We use new biomarker thermal maturity indicators to identify seismic faults in drill core recovered from the Japan Trench subduction zone, which hosted 50 m of shallow slip during theMw9.1 2011 Tohoku-Oki earthquake. Our results show that multiple faults have hosted earthquakes with displacement ≥ 10 m, and each could have hosted many great earthquakes, illustrating an extensive history of great earthquake seismicity that caused large shallow slip. We find that lithologic contrasts in frictional properties do not necessarily determine the likelihood of large shallow slip or seismic hazard.
Emergence of pseudogap from short-range spin-correlations in electron-doped cuprates
Authors: Boschini Fabio , Zonno Marta , Razzoli Elia , Day Ryan P. , Michiardi Matteo , Zwartsenberg Berend , Nigge Pascal , Schneider Michael , da Silva Neto Eduardo H. , Erb Andreas , Zhdanovich Sergey , Mills Arthur K. , Levy Giorgio , Giannetti Claudio , Jones David J. , Damascelli Andrea
Published: January 2020

Complex electron interactions underlie the electronic structure of several families of quantum materials. In particular, the strong electron Coulomb repulsion is considered the key ingredient to describing the emergence of exotic and/or ordered phases of quantum matter, from high-temperature superconductivity to charge- and magnetic-order. However, a comprehensive understanding of fundamental electronic properties of quantum materials is often complicated by the appearance of an enigmatic partial suppression of low-energy electronic states, known as the pseudogap. Here we take advantage of ultrafast angle-resolved photoemission spectroscopy to unveil the temperature evolution of the low-energy density of states in the electron-doped cuprate Nd2-xCexCuO4, an emblematic system where the pseudogap intertwines with magnetic degrees of freedom. Using an optical excitation we drive the electronic system across the pseudogap onset temperature T*, and we report the direct relation between the momentum-resolved pseudogap spectral features and the spin-correlation length with a remarkable sensitivity. This transient approach, corroborated by mean-field model calculations, allows us to establish the pseudogap in electron-doped cuprates as a precursor to the incipient antiferromagnetic order even when long-range antiferromagnetic correlations are not established, as in the case of optimal doping.
B4GALNT1 induces angiogenesis, anchorage independence growth and motility, and promotes tumorigenesis in melanoma by induction of ganglioside GM2/GD2
Authors: Yoshida Hideki , Koodie Lisa , Jacobsen Kari , Hanzawa Ken , Miyamoto Yasuhide , Yamamoto Masato
Published: January 2020

β-1,4-N-Acetyl-Galactosaminyltransferase 1 (B4GALNT1)encodes the key enzyme B4GALNT1 to generate gangliosides GM2/GD2. GM2/GD2 gangliosides are surface glycolipids mainly found on brain neurons as well as peripheral nerves and skin melanocytes and are reported to exacerbate the malignant potential of melanomas. In order to elucidate the mechanism, we performed functional analyses of B4GALNT1-overexpressing cells. We analyzed ganglioside pattern on four melanoma and two neuroblastoma cell lines by high performance liquid chromatography (HPLC). We overexpressed B4GALNT1 in GM2/GD2-negative human melanoma cell line (SH4) and confirmed production of GM2/GD2 by HPLC. They showed higher anchorage independence growth (AIG) in colony formation assay, and exhibited augmented motility.In vitro, cell proliferation was not affected by GM2/GD2 expression.In vivo, GM2/GD2-positive SH4 clones showed significantly higher tumorigenesis in NOD/Scid/IL2Rγ-null mice, and immunostaining of mouse CD31 revealed that GM2/GD2 induced remarkable angiogenesis. No differences were seen in melanoma stem cell and Epithelial-Mesenchymal Transition markers between GM2/GD2-positive and -negative SH4 cells. We therefore concluded that B4GALNT1, and consequently GM2/GD2, enhanced tumorigenesis via induction of angiogenesis, AIG, and cell motility. RNA-Seq suggested periostin as a potential key factor for angiogenesis and AIG. These findings may lead to development of novel therapy for refractory melanoma.
Person-Specific Methods for Characterizing the Course and Temporal Dynamics of Concussion Symptomatology: A Pilot Study
Authors: Rabinowitz Amanda R. , Fisher Aaron J.
Published: January 2020

Better characterization of acute concussion symptomatology is needed in order to advance clinical and scientific understanding of persistent concussion symptoms. This paper aims to illustrate a novel framework for conceptualizing, collecting, and analyzing concussion symptom data. To that end, we describe the temporal and structural dynamics of acute concussion symptoms at the individual-patient level. Ten recently concussion adolescents and young adults completed 20 days of ecological momentary assessment (EMA) of post-concussion symptoms. Follow-up assessments were completed at 3 months post-injury. Network modeling revealed marked heterogeneity across participants. In the overall sample, temporal patterns explained the most variance in light sensitivity (48%) and the least variance in vomiting (5%). About half of the participants had symptom networks that were sparse after controlling for temporal variation. The other individualized symptom networks were densely interconnected clusters of symptoms. Networks were highly idiosyncratic in nature, yet emotional symptoms (nervousness, emotional, sadness), cognitive symptoms (mental fogginess, slowness), and symptoms of hyperacusis (sensitivity to light, sensitivity to noise) tended to cluster together across participants. Person-specific analytic techniques revealed a number of idiosyncratic features of post-concussion symptomatology. We propose applying this framework to future research to better understand individual differences in concussion recovery.
Association of Irregular Pigment Epithelial Detachment in Central Serous Chorioretinopathy with Genetic Variants Implicated in Age-related Macular Degeneration
Authors: Cho Soo Chang , Ryoo Na-Kyung , Ahn Jeeyun , Woo Se Joon , Park Kyu Hyung
Published: January 2020

We evaluated phenotype and genotype correlation of central serous chorioretinopathy (CSC) patients with or without irregular pigment epithelial detachment (PED) on optical coherence tomography (OCT). For CSC, a flat, irregular protrusion of retinal pigment epithelium (RPE) with hyper-reflective sub-RPE fluid on OCT was defined as an irregular PED. Participants were classified into 5 subgroups; (1) total CSC (n = 280) (2) CSC with irregular PED (n = 126) (3) CSC without irregular PED (n = 154) (4) typical choroidal neovascularization (CNV) (n = 203) and (5) polypoidal choroidal vasculopathy (PCV) (n = 135). Ten known major AMD-associated single-nucleotide polymorphisms (SNPs) were analyzed. Age, sex adjusted logistic regression was performed for the association between subgroups. Association analysis between CSC without irregular PED and CNV revealed that significant difference for rs10490924 in ARMS2, rs10737680 in CFH, and marginally significant difference for rs800292 in CFH. Between CSC without irregular PED and PCV, rs10490924, rs10737680, and rs800292 were significantly different. In contrast, CSC with irregular PED and CNV revealed no SNP showing significant difference. Between CSC with irregular PED and PCV, only rs10490924 was significantly different. CSC with irregular PED and CSC without irregular PED revealed significant difference for rs800292, and marginal difference for rs10737680. These findings suggest CSC patients with irregular PED are genetically different from those without irregular PED and may have genetic and pathophysiologic overlap with AMD patients.
Second law analysis with effects of Arrhenius activation energy and binary chemical reaction on nanofluid flow
Authors: Khan Noor Saeed , Kumam Poom , Thounthong Phatiphat
Published: January 2020

The Arrhenius activation energy and binary chemical reaction are taken into account to consider the magnetohydrodynamic mixed convection second grade nanofluid flow through a porous medium in the presence of thermal radiation, heat absorption/generation, buoyancy effects and entropy generation. The items composing of the governing systems are degenerated to nonlinear ordinary differential equations by adopting the appropriate similarity transformations which are computed through Runge-Kutta-Fehlberg (RKF) numerical technique along with Shooting method. The solution is manifested through graphs which provides a detailed explanations of each profile in terms of involved parameters effects. The compared results maintain outstanding approach to the previous papers.
Biosynaptic devices based on chicken egg albumen:graphene quantum dot nanocomposites
Authors: Sung Sihyun , Park Jae Hyeon , Wu Chaoxing , Kim Tae Whan
Published: January 2020

Biosynaptic devices based on chicken egg albumen (CEA):graphene quantum dot (GQD) hybrid nanocomposites were fabricated to achieve stable synaptic behaviors. Current-voltage (I-V) curves for the biosynaptic devices under consecutive negative and positive voltage sweeps showed clockwise pinched hysteresis, which is a critical feature of a biological synapse. The effect of the GQD concentration in the CEA layer on the device performance was studied. The retention time of the biosynaptic devices was relatively constant, maintaining a value above 104 s under ambient conditions. The carrier transport mechanisms of the biosynaptic devices were described and analyzed on the basis of the slopes of the I-V curves and their fittings.
A general covalent binding model between cytotoxic selenocompounds and albumin revealed by mass spectrometry and X-ray absorption spectroscopy
Authors: Zheng Wenyi , He Rui , Boada Roberto , Subirana Maria Angels , Ginman Tobias , Ottosson Håkan , Valiente Manuel , Zhao Ying , Hassan Moustapha
Published: January 2020

Selenocompounds (SeCs) are promising therapeutic agents for a wide range of diseases including cancer. The treatment results are heterogeneous and dependent on both the chemical species and the concentration of SeCs. Moreover, the mechanisms of action are poorly revealed, which most probably is due to the detection methods where the quantification is based on the total selenium as an element. To understand the mechanisms underlying the heterogeneous cytotoxicity of SeCs and to determine their pharmacokinetics, we investigated selenium speciation of six SeCs representing different categories using liquid chromatography-mass spectrometry (LC-MS) and X-ray absorption spectroscopy (XAS) and the cytotoxicity using leukemic cells. SeCs cytotoxicity was correlated with albumin binding degree as revealed by LC-MS and XAS. Further analysis corroborated the covalent binding between selenol intermediates of SeCs and albumin thiols. On basis of the Se-S model, pharmacokinetic properties of four SeCs were for the first time profiled. In summary, we have shown that cytotoxic SeCs could spontaneously transform into selenol intermediates that immediately react with albumin thiols through Se-S bond. The heterogeneous albumin binding degree may predict the variability in cytotoxicity. The present knowledge will also guide further kinetic and mechanistic investigations in both experimental and clinical settings.