bluuebunny/crossref_metadata_2025 huggingface dataset:
Revisiting the tectonic evolution of the Triassic Palaeo-Tethys convergence zone in northern Thailand inferred from detrital zircon U–Pb ages
Authors: Hara Hidetoshi , Tokiwa Tetsuya , Kurihara Toshiyuki , Charoentitirat Thasinee , Sardsud Apsorn
Published: September 2020

Detrital zircon U–Pb ages for sediments in and around the Palaeo-Tethyan convergence zone in northern Thailand provide constraints for tectonic interpretations of the Indochina Block, the Sibumasu Block, the Inthanon Zone accretionary complex and the Nan Back-arc Basin during the Triassic. In sedimentary rocks of the Indochina Block, almost all of the Palaeozoic and Triassic zircons were sourced from the collision zone between the Indochina and South China blocks, and an active continental margin in the western Indochina Block. Sediments of the Sibumasu Block were supplied by erosion of Archaean basement and from the Grenville and the Pan African orogenies, but show no record of Permian to Triassic igneous activity. Accretionary complex sediments have provenances of both the Sukhothai Arc and the Indochina and South China blocks, with detrital zircons of various ages being supplied from crustal uplift and erosion related to the Indosinian I orogeny. Sedimentary rocks of the Nan Back-arc Basin are widely distributed not only in the Nan–Uttaradit but also in northern Sukhothai areas. The origin of the Pha Som Metamorphic Complex and associated formations can be traced to basin-filling sediments in the Nan Back-arc Basin. These detrital zircon U–Pb ages have also allowed identification of the changing tectonic setting in the Palaeo-Tethys convergence zone from the ‘erosion of Proterozoic continental basement’ to ‘Palaeozoic active continental margin in the western Indochina Block’ and ‘Palaeozoic, Permian to Triassic collision zone between the South China and Indochina blocks’ through to ‘Triassic active Sukhothai Arc’.
A reaction–diffusion epidemic model with incubation period in almost periodic environments
Authors: QIANG LIZHONG , WANG BIN-GUO , WANG ZHI-CHENG
Published: September 2020

In this paper, we propose and study an almost periodic reaction–diffusion epidemic model in which disease latency, spatial heterogeneity and general seasonal fluctuations are incorporated. The model is given by a spatially nonlocal reaction–diffusion system with a fixed time delay. We first characterise the upper Lyapunov exponent λ* for a class of almost periodic reaction–diffusion equations with a fixed time delay and provide a numerical method to compute it. On this basis, the global threshold dynamics of this model is established in terms of λ* It is shown that the disease-free almost periodic solution is globally attractive if λ* < 0, while the disease is persistent if λ* > 0. By virtue of numerical simulations, we investigate the effects of diffusion rate, incubation period and spatial heterogeneity on disease transmission.
Boosting Familiarity-Based Memory Decisions in Alzheimer’s Disease: The Importance of Metacognition
Authors: Geurten Marie , Salmon Eric , Willems Sylvie , Bastin Christine
Published: September 2020

Objective:

Recent studies in Alzheimer’s disease (AD) have suggested that AD patients are not always able to rely on their feeling of familiarity to improve their memory decisions to the same extent as healthy participants. This underuse of familiarity in AD could result from a learned reinterpretation of fluency as a poor cue for memory that would prevent them to attribute a feeling of fluency to a previous encounter. The primary goal of this study was to determine whether AD patients could relearn the association between processing fluency and past exposure after being repeatedly exposed to situations where using this association improves the accuracy of their memory decisions.

Method:

Thirty-nine patients with probable AD were recruited and asked to complete several recognition tests. During these tests, participants were put either in a condition where the positive contingency between fluent processing and previous encounters with an item was systematically confirmed (intervention condition) or in a condition where there was no correlation between fluency and prior exposure (control condition). The efficacy of the intervention was evaluated at three time points (baseline, posttest, and 3-month follow-up).

Results:

Our results indicated that all AD patients do not benefit to the same extent from the training. Two variables appeared to influence the likelihood that participants increase and maintain their reliance on the fluency cues after the intervention: the ability to detect the fluency manipulation and the preservation of implicit metacognitive skills.

Conclusion:

These findings indicate the importance of metacognition for inferential attribution processes in memory.
Behavioural characteristics and abdominal obesity among Brazilian shift working women
Authors: Theodoro Heloísa , Bassani Diego Garcia , da Silva Janaína Cristina , Mendes Karina Giane , Cibeira Gabriela Hermann , Schenkel Julia Cigana , Olinto Maria Teresa Anselmo
Published: September 2020

Objective:

To explore the association between behavioural characteristics with the prevalence of abdominal obesity (AO) among a population of Southern Brazilian shift working women.

Design:

A cross-sectional study was conducted. AO was estimated using waist circumference (WC), and it was used to classify women as having AO (WC ≥ 88 cm). Prevalence ratios were estimated using Poisson regression with robust variance.

Setting:

A large plastic utensils company in Southern Brazil.

Participants:

450 female shift workers.

Results:

The prevalence of the AO in the women shift workers was 44·5 % (95 % CI 40·0, 49·2 %). In night shift workers, the prevalence of AO was 56·1 % compared with 40·9 % among hybrid shift workers. After adjustments for covariates, women who were current smokers had a decrease in the prevalence of AO compared with those who never smoked. Women who had three or fewer meals per day had a 46 % increase in the AO prevalence compared with those eating more frequent meals. Night shift work was associated with increase in AO prevalence compared with hybrid shift (PR 1·33; 95 % CI: 1·08, 1·64).

Conclusions:

Our findings indicate that behavioural characteristics are associated with a high prevalence of AO in female shift workers, thus suggesting that behavioural modifications among women working shifts, such as increase in meal frequency and physical activity, may reduce AO.
A Test of the Diatom‐Bound Paleoproxy: Tracing the Isotopic Composition of Nutrient‐Nitrogen Into Southern Ocean Particles and Sediments
Authors: Robinson Rebecca S. , Jones Colin A. , Kelly Roger P. , Love Amanda , Closset Ivia , Rafter Patrick A. , Brzezinski Mark
Published: September 2020

Sedimentary nitrogen isotope (as δ15N) records from the Southern Ocean provide critical constraints on surface nutrient consumption in the past and the role of Southern Ocean biophysical changes in setting atmospheric pCO2. We present a field assessment of how surface nitrate consumption is reflected in δ15N values of total nitrogen and diatom‐bound nitrogen pools of particles and sediments across the Southern Ocean along 170°W during late austral summer. Mixed layer nitrate δ15N values increase northwards associated with greater nitrate drawdown. Particles and sediments are expected to follow this trend. Contrary to expectations, surface ocean particle total nitrogen and diatom‐bound δ15N values decreased northward during the late summer, likely due to recycling of nitrogen and the assimilation of regenerated ammonium, as well as nitrate. The relationship between δ15N values of the total nitrogen and diatom‐bound pools remains relatively constant across this Southern Ocean transect, suggesting that the isotopic composition of these two surface ocean nitrogen pools are largely set by the δ15N value(s) of the assimilated nutrient(s). Surface sediment δ15N values do increase away from the region of maximum biogenic silica deposition, suggesting that the recycled nitrogen isotopic signal observed in late summer particles may not significantly impact the sedimentary record. However, the enrichment in δ15N values of the diatom‐bound pool is greater than what is expected from progressive utilization of the surface nitrate alone and not yet explained.
Identifying Climate Modes Contributing to Sea Surface Salinity Decadal Variation in the North Pacific Ocean
Authors: Chen Jian , Liu Hailong , Bai Chengzu , Yan Hengqian , Lu Kaicheng , Bao Senliang , Liu Kefeng
Published: September 2020

The North Pacific sea surface salinity (SSS) decadal variation (NPSDV) plays key roles in tracing ocean circulation and hydrological cycle, and its contributing climate modes need to be identified. Three data sets, ORAS4, EN4.2.1, and GODAS, were first evaluated. An autoregressive lag 1 (AR‐1) process model, along with spectrum and correlation analysis, was then applied to the most robust SSS data set during 1980–2017. The AR‐1 reconstructed SSS anomalies explain up to 77% and 55% of the first two modes, respectively. As expected, the NPSDV arises from the superposition of SSS variations with different dynamical origins, including the reemergence, Eastern Pacific and Central Pacific El Niño–Southern Oscillation (ENSO) (EP‐ENSO and CP‐ENSO), Aleutian Low (AL), North Pacific Oscillation (NPO), and Kuroshio and Oyashio Extension (KOE) meridional and zonal modes (KOE‐M and KOE‐Z). Its first mode is 50% EP‐ENSO and 32% CP‐ENSO, while the second mode is 58% NPO and 54% CP‐ENSO. Specifically, stronger persistence in salinity explains most of NPSDV variance. The first mode resembles the EP‐ENSO pattern with a positive loading center in the eastern North Pacific, and the second mode resembles the CP‐ENSO (and also NPO) pattern with a positive loading center near the dateline, alike the contrasting EP‐ENSO and CP‐ENSO SSS flavors in the tropics. Besides, a fraction of the first mode notable in the KOE region is controlled by KOE‐Z and KOE‐M as intrinsic oceanic dynamics. The importance of AL to NPSDV, after removing the indirect impact of ENSO, is insignificant. A general NPSDV evolution was lastly revealed.
Drizzle, Turbulence, and Density Currents Below Post Cold Frontal Open Cellular Marine Stratocumulus Clouds
Authors: Ghate Virendra P. , Cadeddu Maria P. , Wood Robert
Published: September 2020

Nine cases of postcold frontal marine stratocumulus clouds exhibiting open cellular mesoscale organization are analyzed to characterize the drizzle, turbulence, and density currents below them. Data collected by the vertically pointing Doppler cloud radar and multiple lidars part of the Atmospheric Radiation Measurement (ARM) Eastern North Atlantic (ENA) site are used in these analyses. A total of 251 drizzle shafts passed over the site with 76 shafts sampled for more than 15 min by the vertically pointing instruments. On average the drizzle shafts were ~18 km wide with below‐cloud drizzle water path of ~40 g m−2, cloud base rain rate of 7.78 mm day−1, and cloud base drizzle modal diameter of 393 μm. The widths of the drizzle shafts did not exhibit any relationship with the cloud base rain rate, below‐cloud drizzle water path, and the total water removed from the cloud. The downdrafts in the lowest 500 m within the drizzle cells strengthened with increasing cloud base rain rates, while the updrafts within drizzle cells did not exhibit this behavior. On average, the surface air density, pressure, water vapor mixing ratio, and wind speed along the background wind during the drizzle shaft were higher by 1.88 g m−3, 8.60 Pa, 0.24 g kg−1, and 1.22 m s−1, respectively, from their background values. On the other hand, the surface air temperature was lower by 0.43 K during the drizzle shaft than its background value. The coincident measurements highlight the drizzle‐turbulence‐surface coupling in these cloud systems.
The G20 Is Investing in Fossil Fuels
Authors: Pardikar Rishika
Published: September 2020

Among the G20, the United States and United Kingdom have invested the most in fossil fuels since the beginning of 2020.
Tracking Dissolved Trace and Heavy Metals in the Ganga River From Source to Sink: A Baseline to Judge Future Changes
Authors: Boral Soumita , Sen Indra Sekhar , Tripathi Aditya , Sharma Bhupendra , Dhar Sanjukta
Published: September 2020

Understanding how dissolved trace elements chemically evolve in the Ganga River from source to sink is important to understand subcatchment contributions and chemical variability across space and time but remains poorly constrained. What exists is site‐specific data sets that are focused on capturing contamination “hotspots.” Here, we present riverine trace element concentrations of 38 targeted locations in the Ganga Basin. Samples in the headwater and the upstream segments of the river were collected during the premonsoon, monsoon, and postmonsoon seasons of 2014, 2015, and 2016, and the downstream samples were collected in 2016. In addition, monthly time‐series samples were collected at a downstream site to capture the geochemical variability at a higher temporal‐resolution. To evaluate the geogenic contributions, groundwater, rainwater, snow, glacier‐ice, and sediment samples were also analyzed. We find that the river chemistry displays a wide spatio‐temporal variability. Headwater samples are characterized by high concentrations of trace elements that are primarily controlled by ice meltwater, intense weathering, and interactions with glacial flour and are therefore geogenic in nature. Moreover, high concentrations of trace metals were also observed in a few localized downstream sites. However, such enriched signals are not persistent further downstream as they get diluted by the joining of large tributaries. We show that the dissolved trace element concentrations in the Ganga River are low compared to existing datasets and are comparable to the global average river water composition. We additionally quantified the present‐day “baseline” concentration ranges to facilitate future water quality assessment in the Ganga Basin.
Mixing Driven by Breaking Nonlinear Internal Waves
Authors: Jones N. L. , Ivey G. N. , Rayson M. D. , Kelly S. M.
Published: September 2020

Non‐linear internal waves (NLIW) are important to processes such as heat transfer, nutrient replenishment and sediment transport on continental shelves. Our unique field observations of shoaling NLIW of elevation revealed a variety of different wave shapes, varying from relatively symmetric waves, to waves with either steepened leading‐ or trailing‐faces; many had evidence of trapped cores. The wave shape was related to the position of maximum density overturns and diapycnal mixing. We observed both shear (where sheared currents overcome the stabilizing effects of stratification) and convective (where the local velocity exceeds the wave propagation speed) instabilities. The elevated diapycnal mixing (>10−3 m2s−1) and heat flux (>500 Wm−2) were predominantly local to the NLIW of elevation packets, and were transported onshore 10s kilometers with the wave packets. We demonstrate that wave steepness may be a useful bulk property for the parameterization of wave‐averaged diapycnal heat flux.
Mobile Pressure Calibrator for the Development of Submarine Geodetic Monitoring Systems
Authors: Machida Yuya , Nishida Shuhei , Kimura Toshinori , Araki Eiichiro
Published: September 2020

Monitoring long‐term vertical seafloor displacements at the centimeter scale using a pressure gauge network in the seismogenic zone is key to understanding the real‐time strength of interplate coupling. The mobile pressure calibrator (MPC) was developed for calibrating a seafloor pressure gauge network with a resolution of less than 1 hPa/year, equivalent to about 1 cm/year. Inherent drift of the seafloor pressure gauges is estimated by comparing the raw observations between the seafloor pressure gauges and the MPC and subsequently subtracting the long‐term pressure data. In October 2018, three in situ pressure measurements were conducted to evaluate the measurement uncertainty of the MPC. The calibrator was placed adjacent to a seafloor pressure gauge, which is installed at a depth of about 1,750 m in the Nankai Trough offshore Japan, and measured the pressure differences between the calibrator and the seafloor pressure gauge. The drift component of the pressure gauge used inside the MPC was estimated and corrected based on calibrations performed in the laboratory before and after the in situ seafloor pressure measurements. The results indicated an uncertainty of 0.04 hPa for the in situ measurements and therefore the possibility of detecting small, long‐term seafloor displacements. We continue to compare the MPC and seafloor pressure gauge deviations over intervals of several months to years and estimate the drift of the seafloor pressure gauge.
A Baseline for Global Weather and Climate Simulations at 1 km Resolution
Authors: Wedi Nils P. , Polichtchouk Inna , Dueben Peter , Anantharaj Valentine G. , Bauer Peter , Boussetta Souhail , Browne Philip , Deconinck Willem , Gaudin Wayne , Hadade Ioan , Hatfield Sam , Iffrig Olivier , Lopez Philippe , Maciel Pedro , Mueller Andreas , Saarinen Sami , Sandu Irina , Quintino Tiago , Vitart Frederic
Published: September 2020

In an attempt to advance the understanding of the Earth's weather and climate by representing deep convection explicitly, we present a global, four‐month simulation (November 2018 to February 2019) with ECMWF's hydrostatic Integrated Forecasting System (IFS) at an average grid spacing of 1.4 km. The impact of explicitly simulating deep convection on the atmospheric circulation and its variability is assessed by comparing the 1.4 km simulation to the equivalent well‐tested and calibrated global simulations at 9 km grid spacing with and without parametrized deep convection. The explicit simulation of deep convection at 1.4 km results in a realistic large‐scale circulation, better representation of convective storm activity, and stronger convective gravity wave activity when compared to the 9 km simulation with parametrized deep convection. Comparison of the 1.4 km simulation to the 9 km simulation without parametrized deep convection shows that switching off deep convection parametrization at a too coarse resolution (i.e., 9 km) generates too strong convective gravity waves. Based on the limited statistics available, improvements to the Madden‐Julian Oscillation or tropical precipitation are not observed at 1.4 km, suggesting that other Earth system model components and/or their interaction are important for an accurate representation of these processes and may well need adjusting at deep convection resolving resolutions. Overall, the good agreement of the 1.4 km simulation with the 9 km simulation with parametrized deep convection is remarkable, despite one of the most fundamental parametrizations being turned off at 1.4 km resolution and despite no adjustments being made to the remaining parametrizations.
The Impact of Resolving Subkilometer Processes on Aerosol‐Cloud Interactions of Low‐Level Clouds in Global Model Simulations
Authors: Terai C. R. , Pritchard M. S. , Blossey P. , Bretherton C. S.
Published: September 2020

Subkilometer processes are critical to the physics of aerosol‐cloud interaction (ACI) but have been dependent on parameterizations in global model simulations. We thus report the strength of ACI in the Ultra‐Parameterized Community Atmosphere Model (UPCAM), a multiscale climate model that uses coarse exterior resolution to embed explicit cloud‐resolving models with enough resolution (250 m horizontal, 20 m vertical) to quasi‐resolve subkilometer eddies. To investigate the impact on ACIs, UPCAM's simulations are compared to a coarser multiscale model with 4 km horizontal resolution. UPCAM produces cloud droplet number concentrations (Nd) and cloud liquid water path (LWP) values that are higher than the coarser model but equally plausible compared to observations. Our analysis focuses on the Northern Hemisphere (20–50°N) oceans, where historical aerosol increases have been largest. We find similarities in the overall radiative forcing from ACIs in the two models, but this belies fundamental underlying differences. The radiative forcing from increases in LWP is weaker in UPCAM, whereas the forcing from increases in Nd is larger. Surprisingly, the weaker LWP increase is not due to a weaker increase in LWP in raining clouds, but a combination of weaker increase in LWP in nonraining clouds and a smaller fraction of raining clouds in UPCAM. The implication is that as global modeling moves toward finer than storm‐resolving grids, nuanced model validation of ACI statistics conditioned on the existence of precipitation and good observational constraints on the baseline probability of precipitation will become key for tighter constraints and better conceptual understanding.
Stat2 stability regulation: an intersection between immunity and carcinogenesis
Authors: Lee Cheol-Jung , An Hyun-Jung , Cho Eun Suh , Kang Han Chang , Lee Joo Young , Lee Hye Suk , Cho Yong-Yeon
Published: September 2020

Signal transducer and activator of transcription (STAT2) is a member of the STAT family that plays an essential role in immune responses to extracellular and intracellular stimuli, including inflammatory reactions, invasion of foreign materials, and cancer initiation. Although the majority of STAT2 studies in the last few decades have focused on interferon (IFN)-α/β (IFNα/β) signaling pathway-mediated host defense against viral infections, recent studies have revealed that STAT2 also plays an important role in human cancer development. Notably, strategic research on STAT2 function has provided evidence that transient regulatory activity by homo- or heterodimerization induces its nuclear localization where it to forms a ternary IFN-stimulated gene factor 3 (ISGF3) complex, which is composed of STAT1 and/or STAT2 and IFN regulatory factor 9 (IEF9). The molecular mechanisms of ISGF3-mediated ISG gene expression provide the basic foundation for the regulation of STAT2 protein activity but not protein quality control. Recently, previously unknown molecular mechanisms of STAT2-mediated cell proliferation via STAT2 protein quality control were elucidated. In this review, we briefly summarize the role of STAT2 in immune responses and carcinogenesis with respect to the molecular mechanisms of STAT2 stability regulation via the proteasomal degradation pathway.
pS421 huntingtin modulates mitochondrial phenotypes and confers neuroprotection in an HD hiPSC model
Authors: Xu Xiaohong , Ng Bryan , Sim Bernice , Radulescu Carola I. , Yusof Nur Amirah Binte Mohammad , Goh Wah Ing , Lin Shuping , Lim John Soon Yew , Cha Yoonjeong , Kusko Rebecca , Kay Chris , Ratovitski Tamara , Ross Christopher , Hayden Michael R. , Wright Graham , Pouladi Mahmoud A.
Published: September 2020

Huntington disease (HD) is a hereditary neurodegenerative disorder caused by mutant huntingtin (mHTT). Phosphorylation at serine-421 (pS421) of mHTT has been shown to be neuroprotective in cellular and rodent models. However, the genetic context of these models differs from that of HD patients. Here we employed human pluripotent stem cells (hiPSCs), which express endogenous full-length mHTT. Using genome editing, we generated isogenic hiPSC lines in which the S421 site in mHTT has been mutated into a phospho-mimetic aspartic acid (S421D) or phospho-resistant alanine (S421A). We observed that S421D, rather than S421A, confers neuroprotection in hiPSC-derived neural cells. Although we observed no effect of S421D on mHTT clearance or axonal transport, two aspects previously reported to be impacted by phosphorylation of mHTT at S421, our analysis revealed modulation of several aspects of mitochondrial form and function. These include mitochondrial surface area, volume, and counts, as well as improved mitochondrial membrane potential and oxidative phosphorylation. Our study validates the protective role of pS421 on mHTT and highlights a facet of the relationship between mHTT and mitochondrial changes in the context of human physiology with potential relevance to the pathogenesis of HD.
A trimeric CrRLK1L-LLG1 complex genetically modulates SUMM2-mediated autoimmunity
Authors: Huang Yanyan , Yin Chuanchun , Liu Jun , Feng Baomin , Ge Dongdong , Kong Liang , Ortiz-Morea Fausto Andres , Richter Julia , Hauser Marie-Theres , Wang Wen-Ming , Shan Libo , He Ping
Published: September 2020

Cell death is intrinsically linked with immunity. Disruption of an immune-activated MAPK cascade, consisting of MEKK1, MKK1/2, and MPK4, triggers cell death and autoimmunity through the nucleotide-binding leucine-rich repeat (NLR) protein SUMM2 and the MAPK kinase kinase MEKK2. In this study, we identify a Catharanthus roseus receptor-like kinase 1-like (CrRLK1L), named LETUM2/MEDOS1 (LET2/MDS1), and the glycosylphosphatidylinositol (GPI)-anchored protein LLG1 as regulators of mekk1-mkk1/2-mpk4 cell death. LET2/MDS1 functions additively with LET1, another CrRLK1L, and acts genetically downstream of MEKK2 in regulating SUMM2 activation. LET2/MDS1 complexes with LET1 and promotes LET1 phosphorylation, revealing an intertwined regulation between different CrRLK1Ls. LLG1 interacts with the ectodomain of LET1/2 and mediates LET1/2 transport to the plasma membrane, corroborating its function as a co-receptor of LET1/2 in the mekk1-mkk1/2-mpk4 cell death pathway. Thus, our data suggest that a trimeric complex consisting of two CrRLK1Ls LET1, LET2/MDS1, and a GPI-anchored protein LLG1 that regulates the activation of NLR SUMM2 for initiating cell death and autoimmunity.
Molecular correlates of cisplatin-based chemotherapy response in muscle invasive bladder cancer by integrated multi-omics analysis
Authors: Taber Ann , Christensen Emil , Lamy Philippe , Nordentoft Iver , Prip Frederik , Lindskrog Sia Viborg , Birkenkamp-Demtröder Karin , Okholm Trine Line Hauge , Knudsen Michael , Pedersen Jakob Skou , Steiniche Torben , Agerbæk Mads , Jensen Jørgen Bjerggaard , Dyrskjøt Lars
Published: September 2020

Overtreatment with cisplatin-based chemotherapy is a major issue in the management of muscle-invasive bladder cancer (MIBC), and currently none of the reported biomarkers for predicting response have been implemented in the clinic. Here we perform a comprehensive multi-omics analysis (genomics, transcriptomics, epigenomics and proteomics) of 300 MIBC patients treated with chemotherapy (neoadjuvant or first-line) to identify molecular changes associated with treatment response. DNA-based associations with response converge on genomic instability driven by a high number of chromosomal alterations, indels, signature 5 mutations and/orBRCA2mutations. Expression data identifies the basal/squamous gene expression subtype to be associated with poor response. Immune cell infiltration and high PD-1 protein expression are associated with treatment response. Through integration of genomic and transcriptomic data, we demonstrate patient stratification to groups of low and high likelihood of cisplatin-based response. This could pave the way for future patient selection following validation in prospective clinical trials.
Emergent solidity of amorphous materials as a consequence of mechanical self-organisation
Authors: Tong Hua , Sengupta Shiladitya , Tanaka Hajime
Published: September 2020

Amorphous solids have peculiar properties distinct from crystals. One of the most fundamental mysteries is the emergence of solidity in such nonequilibrium, disordered state without the protection by long-range translational order. A jammed system at zero temperature, although marginally stable, has solidity stemming from the space-spanning force network, which gives rise to the long-range stress correlation. Here, we show that such nonlocal correlation already appears at the nonequilibrium glass transition upon cooling. This is surprising since we also find that the system suffers from giant anharmonic fluctuations originated from the fractal-like potential energy landscape. We reveal that it is the percolation of the force-bearing network that allows long-range stress transmission even under such circumstance. Thus, the emergent solidity of amorphous materials is a consequence of nontrivial self-organisation of the disordered mechanical architecture. Our findings point to the significance of understanding amorphous solids and nonequilibrium glass transition from a mechanical perspective.
Engineering domain-inlaid SaCas9 adenine base editors with reduced RNA off-targets and increased on-target DNA editing
Authors: Nguyen Tran Minh Thuan , Mohd Khalid Mohd Khairul Nizam , Wang Qi , Walker Jacqueline K. R. , Lidgerwood Grace E. , Dilworth Kimberley L. , Lisowski Leszek , Pébay Alice , Hewitt Alex W.
Published: September 2020

Precision genome engineering has dramatically advanced with the development of CRISPR/Cas base editing systems that include cytosine base editors and adenine base editors (ABEs). Herein, we compare the editing profile of circularly permuted and domain-inlaid Cas9 base editors, and find that on-target editing is largely maintained following their intradomain insertion, but that structural permutation of the ABE can affect differing RNA off-target events. With this insight, structure-guided design was used to engineer an SaCas9 ABE variant (microABE I744) that has dramatically improved on-target editing efficiency and a reduced RNA-off target footprint compared to current N-terminal linked SaCas9 ABE variants. This represents one of the smallest AAV-deliverable Cas9-ABEs available, which has been optimized for robust on-target activity and RNA-fidelity based upon its stereochemistry.
ARe we there yet? Understanding androgen receptor signaling in breast cancer
Authors: Michmerhuizen Anna R. , Spratt Daniel E. , Pierce Lori J. , Speers Corey W.
Published: September 2020

The role of androgen receptor (AR) activation and expression is well understood in prostate cancer. In breast cancer, expression and activation of AR is increasingly recognized for its role in cancer development and its importance in promoting cell growth in the presence or absence of estrogen. As both prostate and breast cancers often share a reliance on nuclear hormone signaling, there is increasing appreciation of the overlap between activated cellular pathways in these cancers in response to androgen signaling. Targeting of the androgen receptor as a monotherapy or in combination with other conventional therapies has proven to be an effective clinical strategy for the treatment of patients with prostate cancer, and these therapeutic strategies are increasingly being investigated in breast cancer. This overlap suggests that targeting androgens and AR signaling in other cancer types may also be effective. This manuscript will review the role of AR in various cellular processes that promote tumorigenesis and metastasis, first in prostate cancer and then in breast cancer, as well as discuss ongoing efforts to target AR for the more effective treatment and prevention of cancer, especially breast cancer.
Hydrogen peroxide diffusion and scavenging shapes mitochondrial network instability and failure by sensitizing ROS-induced ROS release
Authors: Millare Brent , O’Rourke Brian , Trayanova Natalia
Published: September 2020

The mitochondrial network of cardiac cells is finely tuned for ATP delivery to sites of energy demand; however, emergent phenomena, such as mitochondrial transmembrane potential oscillations or propagating waves of depolarization have been observed under metabolic stress. While regenerative signaling by reactive oxygen species (ROS)-induced ROS release (RIRR) has been suggested as a potential trigger, it is unknown how it could lead to widespread responses. Here, we present a novel computational model of RIRR transmission that explains the mechanisms of this phenomenon. The results reveal that superoxide mediates neighbor-neighbor activation of energy-dissipating ion channels, while hydrogen peroxide distributes oxidative stress to sensitize the network to mitochondrial criticality. The findings demonstrate the feasibility of RIRR as a synchronizing factor across the dimensions of the adult heart cell and illustrate how a cascade of failures at the organellar level can scale to impact cell and organ level functions of the heart.
Efficient chemical fixation and defixation cycle of carbon dioxide under ambient conditions
Authors: Hajra Saumen , Biswas Anurag
Published: September 2020

Chemical fixation of CO2 as a C1 feedstock for producing value-added products is an important post-combustion technology reducing the CO2 emission. As it is an irreversible process, not considered for the CO2 capture and release. Overall, these chemical transformations also do not help to mitigate global warming, as the energy consumed in different forms is much higher than the amount of CO2 fixed by chemical reactions. Here we describe the development of re-generable chemical fixation of CO2 by spiroaziridine oxindole, where CO2 is captured (chemical fixation) under catalyst-free condition at room temperature both in aqueous and non-aqueous medium even directly from the slow stream of flue gas producing regioselectively spirooxazolidinyl oxindoles, a potential drug. The CO2-adduct is reversed back to the spiroaziridine releasing CO2 under mild conditions. Further both the fixation-defixation of CO2 can be repeated under near ambient conditions for several cycles in a single loop using a recyclable reagent.
Polar functional group-containing glycolipid CD1d ligands modulate cytokine-biasing responses and prevent experimental colitis
Authors: Inuki Shinsuke , Hirata Natsumi , Kashiwabara Emi , Kishi Junichiro , Aiba Toshihiko , Teratani Toshiaki , Nakamura Wataru , Kojima Yoshimi , Maruyama Toru , Kanai Takanori , Fujimoto Yukari
Published: September 2020

The MHC class I-like molecule CD1d is a nonpolymorphic antigen-presenting glycoprotein, and its ligands include glycolipids, such as α-GalCer. The complexes between CD1d and ligands activate natural killer T cells by T cell receptor recognition, leading to the secretion of various cytokines (IFN-γ, IL-4, IL-17A, etc.). Herein, we report structure–activity relationship studies of α-GalCer derivatives containing various functional groups in their lipid acyl chains. Several derivatives have been identified as potent CD1d ligands displaying higher cytokine induction levels and/or unique cytokine polarization. The studies also indicated that flexibility of the lipid moiety can affect the binding affinity, the total cytokine production level and/or cytokine biasing. Based on our immunological evaluation and investigation of physicochemical properties, we chose bisamide- and Bz amide-containing derivatives 2 and 3, and evaluated their in vivo efficacy in a DSS-induced model of ulcerative colitis. The derivative 3 that exhibits Th2- and Th17-biasing responses, demonstrated significant protective effects against intestinal inflammation in the DSS-induced model, after a single intraperitoneal injection.
Laterality of specific binding ratios on DAT-SPECT for differential diagnosis of degenerative parkinsonian syndromes
Authors: Shigekiyo Taro , Arawaka Shigeki
Published: September 2020

Motor symptoms of Parkinson’s disease (PD) occur unilaterally and progress with asymmetry, while progressive supranuclear palsy (PSP) and multiple system atrophy of the parkinsonism subtype (MSA-P) lack this tendency. We assessed the laterality of specific binding ratios (SBRs) on dopamine transporter single-photon emission computed tomography (DAT-SPECT) for the differential diagnosis of these diseases in 311 PD, 33 PSP, 20 MSA-P, and 137 control patients. The average SBR in PD was higher than that in PSP (P = 0.035). Compared with Hoehn–Yahr (HY) stages, the average SBR in PD with HY stage I was only higher than that in PSP (P < 0.001). SBR laterality in PD with HY stage I was significantly higher than that in PSP (P = 0.001). This difference was not observed in PD with HY stage II. The average and laterality of SBRs in MSA-P were similar to those in PD and PSP. The asymmetry indices were similar among PD, PSP, and MSA-P. These data suggest that PSP shows a pattern of SBRs different from that in PD, attributed to HY stage I in PD. The limited usefulness of DAT-SPECT may be explained by the low discrimination between PD with bilateral motor symptoms and PSP.
Landing mosquitoes bounce when engaging a substrate
Authors: Smith Nicholas M. , Balsalobre Jasmine B. , Doshi Mona , Willenberg Bradley J. , Dickerson Andrew K.
Published: September 2020

In this experimental study we film the landings ofAedes aegyptimosquitoes to characterize landing behaviors and kinetics, limitations, and the passive physiological mechanics they employ to land on a vertical surface. A typical landing involves 1–2 bounces, reducing inbound momentum by more than half before the mosquito firmly attaches to a surface. Mosquitoes initially approach landing surfaces at 0.1–0.6 m/s, decelerating to zero velocity in approximately 5 ms at accelerations as high as 5.5 gravities. Unlike Dipteran relatives, mosquitoes do not visibly prepare for landing with leg adjustments or body pitching. Instead mosquitoes rely on damping by deforming two forelimbs and buckling of the proboscis, which also serves to distribute the impact force, lessening the potential of detection by a mammalian host. The rebound response of a landing mosquito is well-characterized by a passive mass-spring-damper model which permits the calculation of force across impact velocity. The landing force of the average mosquito in our study is approximately 40$$\upmu$$μN corresponding to an impact velocity of 0.24 m/s. The substrate contact velocity which produces a force perceptible to humans, 0.42 m/s, is above 85% of experimentally observed landing speeds.
Rab13 regulates sEV secretion in mutant KRAS colorectal cancer cells
Authors: Hinger Scott A. , Abner Jessica J. , Franklin Jeffrey L. , Jeppesen Dennis K. , Coffey Robert J. , Patton James G.
Published: September 2020

Small extracellular vesicles (sEVs), 50–150 nm in diameter, have been proposed to mediate cell–cell communication with important implications in tumor microenvironment interactions, tumor growth, and metastasis. We previously showed that mutant KRAS colorectal cancer (CRC) cells release sEVs containing Rab13 protein and mRNA. Previous work had shown that disruption of intracellular Rab13 trafficking inhibits epithelial cell proliferation and invasiveness. Here, we show that Rab13 additionally regulates the secretion of sEVs corresponding to both traditional exosomes and a novel subset of vesicles containing both β1-integrin and Rab13. We find that exposure of recipient cells to sEVs from KRAS mutant donor cells increases proliferation and tumorigenesis and that knockdown of Rab13 blocks these effects. Thus, Rab13 serves as both a cargo protein and as a regulator of sEV secretion. Our data support a model whereby Rab13 can mediate its effects on cell proliferation and invasiveness via autocrine and paracrine signaling.
There is a cycle to cycle variation in ovarian response and pre-hCG serum progesterone level: an analysis of 244 consecutive IVF cycles
Authors: Yildiz Sule , Yakin Kayhan , Ata Baris , Oktem Ozgur
Published: September 2020

We aimed to answer one key question, that was not previously addressed as to whether serum progesterone (P4-hCG day) and its co-variates (estradiol (E2-hCG day) and the number of retrieved oocytes) of a given cycle can be predictive of the subsequent cycle when both cycles are consecutive and comparable for the stimulation protocol, gonadotropin dose and duration of stimulation. We analyzed such 244 consecutive (< 6 months) IVF cycles in 122 patients with GnRH agonist long protocol and found that P4, E2 and the number of retrieved oocytes significantly vary between the two cycles. Although P4 increased (ranging from 4.7 to 266.7%) in the 2nd cycle in 61 patients, E2 and the number of retrieved oocytes, which are normally positively correlated with P4 paradoxically decreased in the 41% and 37.7% respectively, of these same 61 patients. When a similar analysis was done in the 54 out of 122 patients (44.3%) in whom serum P4 was decreased in the 2nd cycle, the mean decrease in P4 was − 34.1 ± 23.3% ranging from − 5.26 to − 90.1%. E2 and the number of retrieved oocytes paradoxically increased in the 42.3% and 40.7% of these 54 patients respectively. P4 remained the same only in the 7 (5.7%) of these 122 patients. These findings indicate that late follicular phase serum P4 may change unpredictably in the subsequent IVF cycle. The changes are not always necessarily proportional with ovarian response of previous cycle suggesting that growth characteristics and steroidogenic activities of antral cohorts may exhibit considerable cycle to cycle variations.
Charge transport mechanism in dielectrics: drift and diffusion of trapped charge carriers
Authors: Pil’nik Andrey A. , Chernov Andrey A. , Islamov Damir R.
Published: September 2020

In this study, we developed a continuum theory of the charge transport in dielectrics by trapped electrons and holes, which takes into account two separate contributions of the current of trapped charge carriers: the drift part and the diffusion one. It was shown that drift current is mostly dominant in the bulk, while the diffusion one reaches significant values near contacts. A comparison with other theoretical models and experiments shows a good agreement. The model can be extended to two- and three-dimensional systems. The developed model, formulated in partial differential equations, can be numerically implemented in the finite element method code.
Community detection with node attributes in multilayer networks
Authors: Contisciani Martina , Power Eleanor A. , De Bacco Caterina
Published: September 2020

Community detection in networks is commonly performed using information about interactions between nodes. Recent advances have been made to incorporate multiple types of interactions, thus generalizing standard methods to multilayer networks. Often, though, one can access additional information regarding individual nodes, attributes, or covariates. A relevant question is thus how to properly incorporate this extra information in such frameworks. Here we develop a method that incorporates both the topology of interactions and node attributes to extract communities in multilayer networks. We propose a principled probabilistic method that does not assume any a priori correlation structure between attributes and communities but rather infers this from data. This leads to an efficient algorithmic implementation that exploits the sparsity of the dataset and can be used to perform several inference tasks; we provide an open-source implementation of the code online. We demonstrate our method on both synthetic and real-world data and compare performance with methods that do not use any attribute information. We find that including node information helps in predicting missing links or attributes. It also leads to more interpretable community structures and allows the quantification of the impact of the node attributes given in input.
Comparative analysis of chloroplast genomes in Vasconcellea pubescens A.DC. and Carica papaya L.
Authors: Lin Zhicong , Zhou Ping , Ma Xinyi , Deng Youjin , Liao Zhenyang , Li Ruoyu , Ming Ray
Published: September 2020

The chloroplast genome is an integral part of plant genomes in a species along with nuclear and mitochondrial genomes, contributing to adaptation, diversification, and evolution of plant lineages. In the family Caricaceae, only the Carica papaya chloroplast genome and its nuclear and mitochondrial genomes were sequenced, and no chloroplast genome-wide comparison across genera was conducted. Here, we sequenced and assembled the chloroplast genome of Vasconcellea pubescens A.DC. using Oxford Nanopore Technology. The size of the genome is 158,712 bp, smaller than 160,100 bp of the C. papaya chloroplast genome. And two structural haplotypes, LSC_IRa_SSCrc_IRb and LSC_IRa_SSC_IRb, were identified in both V. pubescens and C. papaya chloroplast genomes. The insertion-deletion mutations may play an important role in Ycf1 gene evolution in family Caricaceae. Ycf2 is the only one gene positively selected in the V. pubescens chloroplast genome. In the C. papaya chloroplast genome, there are 46 RNA editing loci with an average RNA editing efficiency of 63%. These findings will improve our understanding of the genomes of these two crops in the family Caricaceae and will contribute to crop improvement.
New marine data and age accuracy of the Romualdo Formation, Araripe Basin, Brazil
Authors: Melo Robbyson Mendes , Guzmán Juliana , Almeida-Lima Débora , Piovesan Enelise Katia , Neumann Virgínio Henrique de Miranda Lopes , Sousa Ariany de Jesus e
Published: September 2020

A combined biostratigraphic and palaeoecological study of foraminifera, ostracodes and microfacies was carried out on the Aptian in the Sítio Sobradinho section of the Araripe Basin, northeast Brazil. The analysed section represents a deepening-upward sequence with mid-ramp shoal and outer ramp to basin facies associations on a mixed siliciclastic-carbonate marine ramp. The analysed rocks are dominated by Early Cretaceous planktic foraminifera (Hedbergella aptiana, H. praelippa, H. sigali,Blesfucuianacf.cumulus, Microhedbergella miniglobularis, Gorbachikellacf.kugleri, Pseudoguembelitria blakenosensis, Globigerinelloides clavatus,Globigerinelloidesaff.aptiensis,Gubkinellasp. andLoeblichellasp.). Ostracoda fauna is composed mainly ofPattersoncypris crepataandPattersoncypris micropapillosa. The occurrence ofP.crepataassociated with the Aptian planktic foraminifera demonstrates the potential of this ostracode species to date this interval. The planktic foraminifera from the upper Aptian (Microhedbergella miniglobularisZone) of the Araripe Basin show characteristical Tethyan affinities.
Author Correction: One-step Solution Processing of Ag, Au and Pd@MXene Hybrids for SERS
Authors: Satheeshkumar Elumalai , Makaryan Taron , Melikyan Armen , Minassian Hayk , Gogotsi Yury , Yoshimura Masahiro
Published: September 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Exploring the action of RGDV-gemcitabine on tumor metastasis, tumor growth and possible action pathway
Authors: Zhang Xiaoyi , Zhang Jinhuan , Liu Wenchao , Wang Yaonan , Wu Jianhui , Zhao Shurui , Zhao Ming , Peng Shiqi
Published: September 2020

The coupling of Arg-Gly-Asp-Val (RGDV) and gemcitabine led to a hypothesis that the conjugate (RGDV-gemcitabine) could inhibit tumor metastasis. To confirm this hypothesis the activities of RGDV-gemcitabine inhibiting tumor metastasis in vitro and in vivo were presented for the first time. AFM (atomic force microscopy) imaged that RGDV-gemcitabine was able to adhere onto the surface of serum-starved A549 cells, to block the extending of the pseudopodia. Thereby RGDV-gemcitabine was able to inhibit the invasion, migration and adhesion of serum-starved A549 cells in vitro. On C57BL/6 mouse model RGDV-gemcitabine dose dependently inhibited the metastasis of planted tumor towards the lung and the minimal dose was 0.084 µmol/kg/3 days. The decrease of serum TNF-α (tumor necrosis factor), IL-8 (interleukin-8), MMP-2 (matrix metalloprotein-2) and MMP-9 (matrix metalloprotein-9) of the treated C57BL/6 mice was correlated with the action pathway of RGDV-gemcitabine inhibiting the metastasis of the planted tumor towards lung.