bluuebunny/crossref_metadata_2025 huggingface dataset:
The Management of Retirement Savings Among Financially Heterogamous Couples
Authors: Pugliese Maude , Belleau Hélène
Published: December 2020

Retirement scholars (and policy makers) have traditionally assumed spouses share their retirement savings, even when they are financially heterogamous and their individual saving capacities diverge. Recent research, however, has challenged this assumption, emphasising that wealth is unequally distributed within couples. In this study, we contribute to this debate by exploring how often financially heterogamous spouses describe their management of retirement savings as joint and redistributive. Data collected in Québec (Canada) in 2015 show that 28 per cent of couples with an income differential report to balance retirement savings across partners. Building on exchange and institutional theories of conjugal behaviour, we also stress that the prevalence of this practice varies with several factors, including union duration and matrimonial status. These findings suggest policy makers underestimate the size of the population at risk of old age financial vulnerability when assuming lower-income individuals are well prepared for retirement if partnered with a better-off spouse who saves.
A Queer Approach to Understanding LGBT Vulnerability during the COVID-19 Pandemic
Authors: Reid Graeme , Ritholtz Samuel
Published: December 2020

Throughout the COVID-19 pandemic, advocates have argued for the inclusion of lesbian, gay, bisexual, and trans (LGBT) people in humanitarian response efforts. Yet the application of this differential focus has been mixed among international policy guidelines and national programs. This research note details a queer theoretical approach to humanitarian crises that considers the intersectional factors that produce specific vulnerabilities within LGBT communities. We take two examples from distinct LGBT communities during the COVID-19 pandemic to demonstrate the analytical risk of treating the umbrella acronym LGBT, indicating distinct identity groups, as monolithic and not differentiating within identity groups based on other factors. We contend that this monolithic approach risks obviating the way different structural forces further compound precarity during crisis. Thus, we make the case for rooting intersectional approaches in any queer analyses of crisis.
Measles and Scarlet Fever Epidemic Synergy and Evolving Pathogenic Virulence in Victoria, Australia, 1853–1916
Authors: Roberts Phillip M. , Battles Heather T.
Published: December 2020

Four synchronous epidemics of measles and scarlet fever are observed in the historical data collected by colonial authorities in Victoria, Australia from 1853 to 1876, suggesting some sort of synergistic relationship between the two diseases. While epidemics of measles, as recorded by the colonial record keepers, still occurred during the remainder of the study period (until 1916), no further epidemics of scarlet fever occurred after 1876. This is suggestive of a change in Victoria’s disease ecology in the late 1870s. After analysis of the historical data for potential artifactual cases, it does not appear to be the result of confusion in diagnosis and changes in case definitions do not appear to have affected reporting of the causes of death. We conclude that the most likely explanation for the observed pattern is an epidemic synergy that ended after the 1876 epidemic. We hypothesize that this synergistic relationship between measles and scarlet fever in mid-nineteenth-century Victoria ended due to a shift in the dominant group A streptococci (GAS) M-type or the loss of a GAS bacteriophage. Support for this hypothesis comes from observations that other diagnoses associated with group A strep infections also changed their mortality profiles during the 1870s, particularly “Bright’s disease,” a possible descriptor of post-streptococcal glomerulonephritis. We situate the emergence and end of this pattern within the demographic and socioeconomic conditions of the Victorian gold-mining boom in the 1850s to 1870s and postboom changes in fertility, mortality, and housing infrastructure, highlighting the importance of social conditions in disease evolution.
An integrated weed management strategy for the control of horseweed (Conyza canadensis)
Authors: Vanhie Theodore R. , Tardif François J. , Smith Peter , Vazan Saeed , Cowbrough Michael , Swanton Clarence J.
Published: December 2020

Multiple herbicide-resistant populations of horseweed [Conyza canadensis (L.) Cronquist] continue to spread rapidly throughout Ontario, notably in areas where no-till soybean [Glycine max (L.) Merr.] is grown. The occurrence of multiple herbicide resistance within these populations suggests that the future role of herbicide tank mixtures as a means of control will be limited. An integrated weed management strategy utilizing complementary selection pressures is needed to reduce the selection intensity of relying solely on herbicides for control. Field studies were conducted in 2018 and 2019 to test the hypothesis: if fall-seeded cereal rye (Secale cereale L.) can reduce C. canadensis seedling density and suppress seedling growth, then the interaction(s) of complementary selection pressures of tillage, cereal rye, and herbicides would improve the level of C. canadensis control. Laboratory studies were conducted to determine whether the allelopathic compound 2-benzoxazolinone (BOA) affected the root development of C. canadensis seedlings. The interactions observed among multiple selection pressures of tillage, cereal rye, and herbicides were inconsistent between the 2 yr of study. A monoculture of cereal rye seeded in the fall, however, did reduce seedling height and biomass of C. canadensis consistently, but not density. This reduction in seedling height and biomass was likely caused by the allelopathic compound BOA, which reduced seedling root development. Control of C. canadensis seedlings in the spring required the higher registered rates of dicamba or saflufenacil. The addition of shallow fall tillage and the presence of cereal rye did not improve the variability in control observed notably with 2,4-D or the lower rates of saflufenacil or dicamba. With the implementation of complementary weed management strategies, environmental variables in any given year will likely have a direct influence on whether these interactions are additive or synergistic.
Target-site mutation and enhanced metabolism confer resistance to thifensulfuron-methyl in a multiple-resistant redroot pigweed (Amaranthus retroflexus) population
Authors: Cao Yi , Wei Shouhui , Huang Hongjuan , Li Wenyu , Zhang Chaoxian , Huang Zhaofeng
Published: December 2020

Redroot pigweed (Amaranthus retroflexus L.) is a troublesome dicot weed species widely distributed across China. A population of A. retroflexus that survived the recommended label rate of thifensulfuron-methyl was collected from the main soybean [Glycine max (L.) Merr.] production area in China. Whole-plant dose–response assays indicated that the resistant (R) population was highly resistant (61.80-fold) to thifensulfuron-methyl compared with the susceptible (S1 and S2) populations. In vitro acetolactate synthase (ALS) activity experiments showed that the thifensulfuron-methyl I50 value for the R population was 40.17 times higher than that for the S1 population. A preliminary malathion treatment study indicated that the R population might have cytochrome P450–mediated metabolic resistance. The R population exhibited a high level of cross-resistance to representative ALS herbicides (imazethapyr, flumetsulam, and bispyribac-sodium) and multiple resistance to the commonly used protoporphyrinogen oxidase (PPO)-inhibiting herbicides lactofen and fomesafen. Two common mutations, Trp-574-Leu in ALS and Arg-128-Gly in PPO2, were identified within the R population. This study identified possible enhanced metabolism of thifensulfuron-methyl coexisting with target-site mutations in both ALS and PPO2 in a multiple-resistant A. retroflexus population.
Familie als Ressource, Fokus und Kontext therapeutischer Interventionen
Authors: Schöbi Dominik , Munsch Simone
Published: December 2020

Zusammenfassung. Die Familie spielt für die körperliche und psychische Gesundheit eine wichtige Rolle. Familienbeziehungen können die Ursache psychischer Probleme sein oder psychische Probleme verstärken. Sie können aber auch eine wichtige Ressource zur Bewältigung psychischer Probleme sein. Andererseits kann eine akute oder chronische psychische Belastung auch Probleme in Familienbeziehungen verursachen oder verstärken. Der Familienkontext bietet deshalb verschiedenste Ansatzpunkte für therapeutische Interventionen. Die vorliegende Auswahl wissenschaftlicher Beiträge beleuchtet unterschiedliche Facetten von Partnerschaft und Familie sowie deren Relevanz für die Psychotherapie und psychologische Interventionen. Sie umfasst einerseits unmittelbare Interventionsforschung auf Paar- und auf Familienebene, andererseits aber auch die Erforschung von Interaktionsprozessen von Paar- und Eltern-Kind Beziehungen, die Untersuchung des Interventions- und Unterstützungsbedarfs von Müttern von Kleinkindern sowie Forschung zur Ressourcenfunktion der Familie im Kontext einer chronischen Krankheit. Die Beiträge unterstreichen auf vielfältige Weise wie eng verwoben das individuelle und das interpersonelle Funktionsniveau auf Familien- und Paarebene sind und wie therapeutische Interventionen vom Einbezug familiärer oder partnerschaftlicher Prozesse profitieren können.
Implementation of an Alpha Damage Annealing Model for Zircon (U‐Th)/He Thermochronology With Comparison to a Zircon Fission Track Annealing Model
Authors: Guenthner William R.
Published: December 2020

Radiation damage exerts a fundamental control on He diffusion in zircon, which manifests as correlations between (U‐Th)/He date and effective uranium concentration. These correlations can be exploited with modeling to explore long‐term thermal histories. This manuscript focuses on one such model, the zircon radiation damage accumulation and annealing model (ZRDAAM) of Guenthner et al. (2013), https://doi.org/10.2475/03.2013.01, by integrating newly defined alpha damage annealing kinetics measured by Ginster et al. (2019), https://doi.org/10.1016/j.gca.2019.01.033, into ZRDAAM. I explore several consequences of this alpha damage annealing model as it relates to (U‐Th)/He date‐effective uranium (eU) correlations, using representative time‐temperature paths and previously published results. Comparison between the current version of ZRDAAM, which uses fission track annealing, and the new annealing model demonstrates that, for thermal histories with prolonged periods at low temperatures (<50°C), alpha dose annealing kinetics yield slightly younger model dates at low to moderate eU concentrations, older dates at moderate to high eU, and substantially younger dates at the highest eU concentrations. The absolute eU concentrations over which the differences are observed varies for a given thermal history, so these ranges should be interpreted as relative or proportional. Younger model dates at high eU in most thermal histories result from lower amounts of annealing that occur with the Ginster et al. (2019) alpha dose annealing kinetics. This annealing model comparison illustrates that the choice of annealing kinetics has the greatest influence over model output for thermal histories involving either prolonged time periods in the 200–300°C temperature window, or a late‐stage reheating event.
Nitrification and Nitrous Oxide Production in the Offshore Waters of the Eastern Tropical South Pacific
Authors: Santoro Alyson E. , Buchwald Carolyn , Knapp Angela N. , Berelson William M. , Capone Douglas G. , Casciotti Karen L.
Published: December 2020

Marine oxygen deficient zones are dynamic areas of microbial nitrogen cycling. Nitrification, the microbial oxidation of ammonia to nitrate, plays multiple roles in the biogeochemistry of these regions, including production of the greenhouse gas nitrous oxide (N2O). We present here the results of two oceanographic cruises investigating nitrification, nitrifying microorganisms, and N2O production and distribution from the offshore waters of the Eastern Tropical South Pacific. On each cruise, high‐resolution measurements of ammonium ([NH4+]), nitrite ([NO2−]), and N2O were combined with 15N tracer‐based determination of ammonia oxidation, nitrite oxidation, nitrate reduction, and N2O production rates. Depth‐integrated inventories of NH4+ and NO2− were positively correlated with one another and with depth‐integrated primary production. Depth‐integrated ammonia oxidation rates were correlated with sinking particulate organic nitrogen flux but not with primary production; ammonia oxidation rates were undetectable in trap‐collected sinking particulate material. Nitrite oxidation rates exceeded ammonia oxidation rates at most mesopelagic depths. We found positive correlations between archaeal amoA genes and ammonia oxidation rates and between Nitrospina‐like 16S rRNA genes and nitrite oxidation rates. N2O concentrations in the upper oxycline reached values of >140 nM, even at the western extent of the cruise track, supporting air‐sea fluxes of up to 1.71 μmol m−2 day−1. Our results suggest that a source of NO2− other than ammonia oxidation may fuel high rates of nitrite oxidation in the offshore Eastern Tropical South Pacific and that air‐sea fluxes of N2O from this region may be higher than previously estimated.
Evolution of Global Lightning in the Transition From Cold to Warm Phase Preceding Two Super El Niño Events
Authors: Williams E. , Bozóki T. , Sátori G. , Price C. , Steinbach P. , Guha A. , Liu Y. , Beggan C. D. , Neska M. , Boldi R. , Atkinson M.
Published: December 2020

Multistation observations of Schumann resonance (SR) intensity document common behavior in the evolution of continental‐scale lightning activity in two super El Niño events, occurring in 1997/98 and 2015/16. The vertical electric field component of SR at Nagycenk, Hungary and the two horizontal magnetic field components in Rhode Island, USA in 1997, and in 2014–2015, the two horizontal magnetic field components at Hornsund, Svalbard and Eskdalemuir, United Kingdom as well as in Boulder Creek, California and Alberta, Canada exhibit considerable increases in SR intensity from some tens of percent up to a few hundred percents in the transition months preceding the two super El Niño events. The UT time distribution of anomalies in SR intensity indicates that in 1997 the lightning activity increases mainly in Southeast Asia, the Maritime Continent and India, i.e. the Asian chimney region. On the other hand, a global response in lightning is indicated by the anomalies in SR intensity in 2014 and 2015. SR‐based results are strengthened by comparison to independent lightning observations from the Optical Transient Detector and the World Wide Lightning Location Network, which also exhibit increased lightning activity in the transition months. The increased lightning is attributable to increased instability due to thermodynamic disequilibrium between the surface and the midtroposphere during the transition. The main conclusion is that variations in SR intensity may act as a precursor for the occurrence and magnitude of these extreme climate events, and in keeping with earlier findings, as a precursor to maxima in global surface air temperature.
Interannual Variability of Precipitation Recycle Ratio Over the Tibetan Plateau
Authors: Zhao Yin , Zhou Tianjun
Published: December 2020

The water cycle over the Tibetan Plateau (TP) is vital to the regional and downstream climate and ecosystem. Clarifying the water cycle process and its interannual variability mechanism over the TP is important for the climate change adaptation activities. However, our current knowledge about the precipitation recycle ratio over the TP and its interannual variation remains inconclusive. Using the advanced reanalysis data ERA5 of the high resolution and a bulk model method, the water cycle over the TP is estimated in terms of the climatology and interannual variability. The climatic precipitation recycle ratio over the TP in summer is 23%. The reason for the contradictory conclusions between Curio et al. (2015, https://doi.org/10.5194/esd-6-109-2015) and other studies reviewed is analyzed and found to be related to the different definitions of the precipitation recycle ratio associated with the atmospheric water vapor mixture. The interannual variability of the precipitation recycle ratio over the TP in summer is significantly and negatively related with the Niño 3.4 index in the preceding winter. The precipitation recycle ratio decreases to 21.4% due to the more moisture inflow in the El Niño decaying summer. The change in the recycle ratio induced by the preceding El Niño events explains 60% of its interannual variability. The response of precipitation recycle ratio over the TP in summer to the preceding El Niño and La Niña events is asymmetric. Our study is conductive to reach the consensus on the climatic precipitation recycle ratio over the TP and advance our knowledge about its interannual variability mechanism.
Factors Determining the Natural Fresh‐Salt Groundwater Distribution in Deltas
Authors: van Engelen Joeri , Bierkens Marc F. P. , Delsman Joost R. , Oude Essink Gualbert H. P.
Published: December 2020

Most river deltas are densely populated areas with intensive agriculture. The increased shortage of fresh surface water that results from rising demands are expected to lead to increased groundwater pumping, which leads to sea water intrusion. To correctly project the future of fresh groundwater resources in deltas, knowing the current fresh‐salt groundwater distribution is a prerequisite. However, uncertainties about these distributions and their drivers are large. To understand these uncertainties, we conducted a global sensitivity analysis of a complex three‐dimensional variable‐density groundwater model of a synthetic delta, simulating the effect of the last glacial low stand and the subsequent marine transgression. The analysis is unique in its wide range of geometries, hydrogeological parameterizations, and boundary conditions analyzed, making it representative for a large number of deltas worldwide. We find that the aquifer hydraulic conductivity is the most uncertain input and has a strong nonmonotonous effect on the total salt mass onshore. The calculated fresh‐salt groundwater distributions were classified into five classes and compared to real‐world case studies. We find that salinity inversions occur in deltaic systems with high representative system anisotropies as a remnant of a marine transgression. These salinity inversions were observed in half of the real‐world cases, indicating that their fresh‐salt groundwater distributions are not in a dynamic equilibrium. We conclude that it is very likely that past marine transgressions are still reflected in the current fresh‐salt groundwater distributions in deltas. This makes paleo‐groundwater modeling a prerequisite for effective simulation of present‐day groundwater salinity distributions in these systems.
A Synthetic Data Set Inspired by Satellite Altimetry and Impacts of Sampling on Global Spaceborne Discharge Characterization
Authors: Sikder Md. Safat , Bonnema Matthew , Emery Charlotte M. , David Cédric H. , Lin Peirong , Pan Ming , Biancamaria Sylvain , Gierach Michelle M.
Published: December 2020

Despite being a critical component of Earth's water cycle, much remains unknown about freshwater fluxes in the world's rivers. Discharge can be estimated in situ by monitoring water surface elevation yet the declining worldwide coverage of gauges makes global discharge quantification challenging. Numerous studies have shown that satellite radar altimetry could provide global discharge estimates. In anticipation such groundbreaking datasets, one key question remains unanswered: how accurately could the various orbital configurations of altimetry missions capture global discharge distributions under optimal retrieval conditions? We here generate an idealized synthetic global discharge data set following mission orbits, and present the first evaluation of various spatiotemporal sampling strategies on global discharge distribution estimation. Our data are produced by superimposing six measurement footprints representing nine altimetry missions onto existing global discharge simulations. While this approach assumes accurate simulations and ignores uncertainties in spaceborne discharge estimation, it allows for an upper limit assessment of how satellite missions might capture global characteristics of hydrographs. We show that most orbits used could lead to accurate global mean flow distribution (<7%), which was expected but never demonstrated. We also find that accurate distributions of minimum flow (respectively, maximum flow and peak flow duration) require revisit times more frequent than 10 (respectively, 5 and 5) days, that is, finer than allowed by existing orbital strategies, and that global extreme discharge and peak flow distributions rely on temporal frequency rather than spatial coverage. Our analysis could inform future mission development and our data set be used to support potential global gap‐filling experiments.
Building inner ears: recent advances and future challenges for in vitro organoid systems
Authors: van der Valk Wouter H. , Steinhart Matthew R. , Zhang Jingyuan , Koehler Karl R.
Published: December 2020

While inner ear disorders are common, our ability to intervene and recover their sensory function is limited. In vitro models of the inner ear, like the organoid system, could aid in identifying new regenerative drugs and gene therapies. Here, we provide a perspective on the status of in vitro inner ear models and guidance on how to improve their applicability in translational research. We highlight the generation of inner ear cell types from pluripotent stem cells as a particularly promising focus of research. Several exciting recent studies have shown how the developmental signaling cues of embryonic and fetal development can be mimicked to differentiate stem cells into “inner ear organoids” containing otic progenitor cells, hair cells, and neurons. However, current differentiation protocols and our knowledge of embryonic and fetal inner ear development in general, have a bias toward the sensory epithelia of the inner ear. We propose that a more holistic view is needed to better model the inner ear in vitro. Moving forward, attention should be made to the broader diversity of neuroglial and mesenchymal cell types of the inner ear, and how they interact in space or time during development. With improved control of epithelial, neuroglial, and mesenchymal cell fate specification, inner ear organoids would have the ability to truly recapitulate neurosensory function and dysfunction. We conclude by discussing how single-cell atlases of the developing inner ear and technical innovations will be critical tools to advance inner ear organoid platforms for future pre-clinical applications.
Phosphorylation of eIF2α signaling pathway attenuates obesity-induced non-alcoholic fatty liver disease in an ER stress and autophagy-dependent manner
Authors: Li Jie , Li Xinle , Liu Daquan , Zhang Shiqi , Tan Nian , Yokota Hiroki , Zhang Ping
Published: December 2020

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder and frequently exacerbates in postmenopausal women. In NAFLD, the endoplasmic reticulum (ER) plays an important role in lipid metabolism, in which salubrinal is a selective inhibitor of eIF2α de-phosphorylation in response to ER stress. To determine the potential mechanism of obesity-induced NAFLD, we employed salubrinal and evaluated the effect of ER stress and autophagy on lipid metabolism. Ninety-five female C57BL/6 mice were randomly divided into five groups: standard chow diet, high-fat (HF) diet, HF with salubrinal, HF with ovariectomy, and HF with ovariectomy and salubrinal. All mice except for SC were given HF diet. After the 8-week obesity induction, salubrinal was subcutaneously injected for the next 8 weeks. The expression of ER stress and autophagy markers was evaluated in vivo and in vitro. Compared to the normal mice, the serum lipid level and adipose tissue were increased in obese mice, while salubrinal attenuated obesity by blocking lipid disorder. Also, the histological severity of hepatic steatosis and fibrosis in the liver and lipidosis was suppressed in response to salubrinal. Furthermore, salubrinal inhibited ER stress by increasing the expression of p-eIF2α and ATF4 with a decrease in the level of CHOP. It promoted autophagy by increasing LC3II/I and inhibiting p62. Correlation analysis indicated that lipogenesis in the development of NAFLD was associated with ER stress. Collectively, we demonstrated that eIF2α played a key role in obesity-induced NAFLD, and salubrinal alleviated hepatic steatosis and lipid metabolism by altering ER stress and autophagy through eIF2α signaling.
SOX9-activated FARSA-AS1 predetermines cell growth, stemness, and metastasis in colorectal cancer through upregulating FARSA and SOX9
Authors: Zhou Taicheng , Wu Lili , Ma Ning , Tang Fuxin , Yu Zhuomin , Jiang Zhipeng , Li Yingru , Zong Zhen , Hu Kunpeng
Published: December 2020

SRY-box transcription factors (SOXs) are effective inducers for the formation of stem-like phenotypes. As a member of SOX family, SOX9 (SRY-box transcription factor 9) has been reported to be highly expressed and exert oncogenic functions in multiple human cancers. In this study, we hypothesized that SOX9 could regulate the function of cancer stem/initiating cells (CSCs) to further facilitate the progression of colorectal cancer (CRC). Then, stable transfection of shRNAs was used to silence indicated genes. Loss-of-function experiments were conducted to demonstrate the in vitro function of CRC cells. In vivo study was conducted to determine the changes in tumorigenesis and metastasis in vivo. Bioinformatics analyses and mechanistic experiments were employed to explore the downstream molecules. Presently, GEPIA data indicated that SOX9 was upregulated in 275 COAD (colon adenocarcinoma) samples relative to 349 normal tissues. Besides, we also proved the upregulation of SOX9 in CRC cell lines (HCT15, SW480, SW1116, and HT-29) compared to normal NCM-460 cells. Silencing of SOX9 suppressed cell growth, stemness, migration, and invasion. Mechanistically, SOX9 activated the transcription of lncRNA phenylalanyl-tRNA synthetase subunit alpha antisense RNA 1 (FARSA-AS1), while FARSA-AS1 elevated SOX9 in turn by absorbing miR-18b-5p and augmented FARSA via sequestering miR-28-5p. Furthermore, loss of FARSA-AS1 hindered malignant phenotypes in vitro and blocked tumor growth and metastasis in vivo. Notably, we testified that FARSA-AS1 aggravated the malignancy in CRC by enhancing SOX9 and FARSA. Our study unveiled a mechanism of SOX9-FARSA-AS1-SOX9/FARSA loop in CRC, which provides some clews of promising targets for CRC.
Sirtuin 1-dependent regulation of high mobility box 1 in hypoxia–reoxygenated brain microvascular endothelial cells: roles in neuronal amyloidogenesis
Authors: Lee Young-Sun , Choi Ji-Young , Mankhong Sakulrat , Moon Sohee , Kim Sujin , Koh Young Ho , Kim Ji-Hye , Kang Ju-Hee
Published: December 2020

Hypoxia–reperfusion injury is one of the major risk factors for neurodegeneration. However, it is unclear whether ischaemic damage in brain microvascular endothelial cells plays roles in neurodegeneration, particularly in the amyloidogenic changes contributing to the development of Alzheimer’s disease (AD) pathologies. Therefore, we investigated the roles of hypoxia–reoxygenation (H/R)-induced release of high mobility group box protein 1 (HMGB1), a risk molecule for AD pathogenesis in the ischaemic damaged brain, from human brain microvascular endothelial cells (HBMVECs) in neuronal amyloid-beta (Aβ) production. H/R increased nuclear–cytosolic translocation and secretion of HMGB1 in HBMVECs, along with increased permeability and HMGB1-dependent p-c-Jun activation. In addition, H/R increased the expression of Sirtuin 1 (Sirt1), coincident with an increase of intracellular Sirt1–HMGB1 binding in HBMVECs. H/R increased the acetylation of HMGB1 and extracellular secretion, which was significantly inhibited by Sirt1 overexpression. Furthermore, Sirt1 contributed to autophagy-mediated endogenous HMGB1 degradation. More importantly, treatment of neuronal cells with conditioned medium from H/R-stimulated HBMVECs (H/R-CM) activated their amyloidogenic pathways. The neuronal amyloidogenic changes (i.e. increased levels of extracellular Aβ40 and Aβ42) by H/R-CM from HBMVECs were further increased by Sirt1 inhibition, which was significantly suppressed by neutralization of the HMGB1 in H/R-CM. Collectively, our results suggest that HMGB1 derived from H/R-stimulated HBMVECs contributes to amyloidogenic pathways in neurons playing roles in the pathogenesis of AD, which are regulated by endothelial Sirt1.
Singular magnetic anisotropy in the nematic phase of FeSe
Authors: Zhou Rui , Scherer Daniel D. , Mayaffre Hadrien , Toulemonde Pierre , Ma Mingwei , Li Yuan , Andersen Brian M. , Julien Marc-Henri
Published: December 2020

FeSe is arguably the simplest, yet the most enigmatic, iron-based superconductor. Its nematic but non-magnetic ground state is unprecedented in this class of materials and stands out as a current puzzle. Here, our nuclear magnetic resonance measurements in the nematic state of mechanically detwinned FeSe reveal that both the Knight-shift and the spin–lattice relaxation rate 1/T1 possess an in-plane anisotropy opposite to that of the iron pnictides LaFeAsO and BaFe2As2. Using a microscopic electron model that includes spin–orbit coupling, our calculations show that an opposite quasiparticle weight ratio between the dxz and dyz orbitals leads to an opposite anisotropy of the orbital magnetic susceptibility, which explains our Knight-shift results. We attribute this property to a different nature of nematic order in the two compounds, predominantly bond type in FeSe and onsite ferro-orbital in pnictides. The T1 anisotropy is found to be inconsistent with existing neutron scattering data in FeSe, showing that the spin fluctuation spectrum reveals surprises at low energy, possibly from fluctuations that do not break C4 symmetry. Therefore, our results reveal that important information is hidden in these anisotropies and they place stringent constraints on the low-energy spin correlations as well as on the nature of nematicity in FeSe.
Efficient hybrid de novo assembly of human genomes with WENGAN
Authors: Di Genova Alex , Buena-Atienza Elena , Ossowski Stephan , Sagot Marie-France
Published: December 2020

Generating accurate genome assemblies of large, repeat-rich human genomes has proved difficult using only long, error-prone reads, and most human genomes assembled from long reads add accurate short reads to polish the consensus sequence. Here we report an algorithm for hybrid assembly, WENGAN, that provides very high quality at low computational cost. We demonstrate de novo assembly of four human genomes using a combination of sequencing data generated on ONT PromethION, PacBio Sequel, Illumina and MGI technology. WENGAN implements efficient algorithms to improve assembly contiguity as well as consensus quality. The resulting genome assemblies have high contiguity (contig NG50: 17.24–80.64 Mb), few assembly errors (contig NGA50: 11.8–59.59 Mb), good consensus quality (QV: 27.84–42.88) and high gene completeness (BUSCO complete: 94.6–95.2%), while consuming low computational resources (CPU hours: 187–1,200). In particular, the WENGAN assembly of the haploid CHM13 sample achieved a contig NG50 of 80.64 Mb (NGA50: 59.59 Mb), which surpasses the contiguity of the current human reference genome (GRCh38 contig NG50: 57.88 Mb).
Iron elevates mesenchymal and metastatic biomarkers in HepG2 cells
Authors: Mehta Kosha J. , Sharp Paul A.
Published: December 2020

Liver iron excess is observed in several chronic liver diseases and is associated with the development of hepatocellular carcinoma (HCC). However, apart from oxidative stress, other cellular mechanisms by which excess iron may mediate/increase HCC predisposition/progression are not known. HCC pathology involves epithelial to mesenchymal transition (EMT), the basis of cancer phenotype acquisition. Here, the effect of excess iron (holo-transferrin 0–2 g/L for 24 and 48 h) on EMT biomarkers in the liver-derived HepG2 cells was investigated. Holo-transferrin substantially increased intracellular iron. Unexpectedly, mRNA and protein expression of the epithelial marker E-cadherin either remained unaltered or increased. The mRNA and protein levels of metastasis marker N-cadherin and mesenchymal marker vimentin increased significantly. While the mRNA expression of EMT transcription factors SNAI1 and SNAI2 increased and decreased, respectively after 24 h, both factors increased after 48 h. The mRNA expression of TGF-β (EMT-inducer) showed no significant alterations. In conclusion, data showed direct link between iron and EMT. Iron elevated mesenchymal and metastatic biomarkers in HepG2 cells without concomitant decrement in the epithelial marker E-cadherin and altered the expression of the key EMT-mediating transcription factors. Such studies can help identify molecular targets to devise iron-related adjunctive therapies to ameliorate HCC pathophysiology.
Feasibility of continuous fever monitoring using wearable devices
Authors: Smarr Benjamin L. , Aschbacher Kirstin , Fisher Sarah M. , Chowdhary Anoushka , Dilchert Stephan , Puldon Karena , Rao Adam , Hecht Frederick M. , Mason Ashley E.
Published: December 2020

Elevated core temperature constitutes an important biomarker for COVID-19 infection; however, no standards currently exist to monitor fever using wearable peripheral temperature sensors. Evidence that sensors could be used to develop fever monitoring capabilities would enable large-scale health-monitoring research and provide high-temporal resolution data on fever responses across heterogeneous populations. We launched the TemPredict study in March of 2020 to capture continuous physiological data, including peripheral temperature, from a commercially available wearable device during the novel coronavirus pandemic. We coupled these data with symptom reports and COVID-19 diagnosis data. Here we report findings from the first 50 subjects who reported COVID-19 infections. These cases provide the first evidence that illness-associated elevations in peripheral temperature are observable using wearable devices and correlate with self-reported fever. Our analyses support the hypothesis that wearable sensors can detect illnesses in the absence of symptom recognition. Finally, these data support the hypothesis that prediction of illness onset is possible using continuously generated physiological data collected by wearable sensors. Our findings should encourage further research into the role of wearable sensors in public health efforts aimed at illness detection, and underscore the importance of integrating temperature sensors into commercially available wearables.
Opisthobranch grazing results in mobilisation of spherulous cells and re-allocation of secondary metabolites in the sponge Aplysina aerophoba
Authors: Wu Yu-Chen , García-Altares María , Pintó Berta , Ribes Marta , Hentschel Ute , Pita Lucía
Published: December 2020

Sponges thrive in marine benthic communities due to their specific and diverse chemical arsenal against predators and competitors. Yet, some animals specifically overcome these defences and use sponges as food and home. Most research on sponge chemical ecology has characterised crude extracts and investigated defences against generalist predators like fish. Consequently, we know little about chemical dynamics in the tissue and responses to specialist grazers. Here, we studied the response of the sponge Aplysina aerophoba to grazing by the opisthobranch Tylodina perversa, in comparison to mechanical damage, at the cellular (via microscopy) and chemical level (via matrix-assisted laser desorption/ionization imaging mass spectrometry, MALDI-imaging MS). We characterised the distribution of two major brominated alkaloids in A. aerophoba, aerophobin-2 and aeroplysinin-1, and identified a generalised wounding response that was similar in both wounding treatments: (i) brominated compound-carrying cells (spherulous cells) accumulated at the wound and (ii) secondary metabolites reallocated to the sponge surface. Upon mechanical damage, the wound turned dark due to oxidised compounds, causing T. perversa deterrence. During grazing, T. perversa’s way of feeding prevented oxidation. Thus, the sponge has not evolved a specific response to this specialist predator, but rather relies on rapid regeneration and flexible allocation of constitutive defences.
Poor oral hygiene and dental caries predict high mortality rate in hemodialysis: a 3-year cohort study
Authors: Mizutani Koji , Mikami Risako , Gohda Tomohito , Gotoh Hiromichi , Aoyama Norio , Matsuura Takanori , Kido Daisuke , Takeda Kohei , Izumi Yuichi , Sasaki Yoshiyuki , Iwata Takanori
Published: December 2020

The aim of this study was to investigate the impact of oral hygiene, periodontal diseases, and dental caries on all-cause mortality in hemodialysis. This prospective cohort study included 266 patients with end-stage renal disease who were undergoing hemodialysis. Medical interviews, blood biochemical tests, and comprehensive dental examinations including periodontal pocket examination on all teeth and dental plaque accumulation by debris index-simplified (DI-S), were performed. Survival rates were assessed at a 3-year follow-up. Overall, 207 patients were included in the longitudinal analysis, and 38 subjects died during the follow-up period. Cox proportional hazards analysis of the multivariate model demonstrated that the highest tertile of DI-S had a significantly higher risk of all-cause mortality than the lowest two tertiles after adjustment for age, sex, smoking habit, body mass index, diabetes, prior cardiovascular disease, hemodialysis vintage, high sensitivity C-reactive protein, albumin, and number of remaining teeth (hazard ratio, 3.04; 95% confidence interval, 1.50–6.17; p = 0.002). Moreover, the number of decayed teeth significantly increased the hazard ratio to 1.21 (95% confidence interval, 1.06.1.37; p = 0.003). This study suggests that accumulated dental plaque and untreated decay, but not periodontal disease, may be independently associated with all-cause mortality in patients undergoing hemodialysis.
Biodegradation of selected hydrocarbons by novel bacterial strains isolated from contaminated Arabian Gulf sediment
Authors: Al-Thukair Assad Ahmed , Malik Karim , Nzila Alexis
Published: December 2020

Three strains of novel bacteria were isolated from oil-contaminated sediment from the Arabian Gulf (Brevibacillus brevis T2C2008, Proteus mirabilis T2A12001, and Rhodococcus quinshengi TA13008). The isolated strains were tested for their degrading efficacy of low and high molecular hydrocarbon (naphthalene and pyrene). The efficacy of the two-hydrocarbon degradation by the isolates bacterial was determined at a temperature of 25 °C and 37 °C and pH of 5.0 and 9.0. In inoculated media at 37 °C, Rhodococcus qinshengi fully metabolized naphthalene and degrade 56% of pyrene. Brevibacillus brevis break down over 80% of naphthalene at room temperatures (25 °C). However, it was found that P. mirabilis and R. qinshengi biodegraded nearly 94% of naphthalene in the incubated media. The capacity for pyrene and naphthalene degradation in varying pH and temperature conditions was shown to be significant in Rhodococcus qinshengi because of its mineralization exceeding 50% across the tested pH and temperature. This implies that the isolated strains are ideal for biodegradation of contaminated sediment with naphthalene and pyrene.
Liquid temperature prediction in bubbly flow using ant colony optimization algorithm in the fuzzy inference system as a trainer
Authors: Babanezhad Meisam , Behroyan Iman , Nakhjiri Ali Taghvaie , Marjani Azam , Heydarinasab Amir , Shirazian Saeed
Published: December 2020

In the current research paper a novel hybrid model combining first-principle and artificial intelligence (AI) was developed for simulation of a chemical reactor. We study a 2-dimensional reactor with heating sources inside it by using computational fluid dynamics (CFD). The type of considered reactor is bubble column reactor (BCR) in which a two-phase system is created. Results from CFD were analyzed in two different stages. The first stage, which is the learning stage, takes advantage of the swarm intelligence of the ant colony. The second stage results from the first stage, and in this stage, the predictions are according to the previous stage. This stage is related to the fuzzy logic system, and the ant colony optimization learning framework is build-up this part of the model. Ants movements or swarm intelligence of ants lead to the optimization of physical, chemical, or any kind of processes in nature. From point to point optimization, we can access a kind of group optimization, meaning that a group of data is studied and optimized. In the current study, the swarm intelligence of ants was used to learn the data from CFD in different parts of the BCR. The learning was also used to map the input and output data and find out the complex connection between the parameters. The results from mapping the input and output data show the full learning framework. By using the AI framework, the learning process was transferred into the fuzzy logic process through membership function specifications; therefore, the fuzzy logic system could predict a group of data. The results from the swarm intelligence of ants and fuzzy logic suitably adapt to CFD results. Also, the ant colony optimization fuzzy inference system (ACOFIS) model is employed to predict the temperature distribution in the reactor based on the CFD results. The results indicated that instead of solving Navier–Stokes equations and complex solving procedures, the swarm intelligence could be used to predict a process. For better comparisons and assessment of the ACOFIS model, this model is compared with the genetic algorithm fuzzy inference system (GAFIS) and Particle swarm optimization fuzzy inference system (PSOFIS) method with regards to model accuracy, pattern recognition, and prediction capability. All models are at a similar level of accuracy and prediction ability, and the prediction time for all models is less than one second. The results show that the model’s accuracy with low computational learning time can be achieved with the high number of CIR (0.5) when the number of inputs ≥ 4. However, this finding is vice versa, when the number of inputs < 4. In this case, the CIR number should be 0.2 to achieve the best accuracy of the model. This finding could also highlight the importance of sensitivity analysis of tuning parameters to achieve an accurate model with a cost-effective computational run.
Combined PI3Kα-mTOR Targeting of Glioma Stem Cells
Authors: Eckerdt Frank D. , Bell Jonathan B. , Gonzalez Christopher , Oh Michael S. , Perez Ricardo E. , Mazewski Candice , Fischietti Mariafausta , Goldman Stewart , Nakano Ichiro , Platanias Leonidas C.
Published: December 2020

Glioblastoma (GBM) is the most common and lethal primary intrinsic tumour of the adult brain and evidence indicates disease progression is driven by glioma stem cells (GSCs). Extensive advances in the molecular characterization of GBM allowed classification into proneural, mesenchymal and classical subtypes, and have raised expectations these insights may predict response to targeted therapies. We utilized GBM neurospheres that display GSC characteristics and found activation of the PI3K/AKT pathway in sphere-forming cells. The PI3Kα selective inhibitor alpelisib blocked PI3K/AKT activation and inhibited spheroid growth, suggesting an essential role for the PI3Kα catalytic isoform. p110α expression was highest in the proneural subtype and this was associated with increased phosphorylation of AKT. Further, employing the GBM BioDP, we found co-expression of PIK3CA with the neuronal stem/progenitor marker NES was associated with poor prognosis in PN GBM patients, indicating a unique role for PI3Kα in PN GSCs. Alpelisib inhibited GSC neurosphere growth and these effects were more pronounced in GSCs of the PN subtype. The antineoplastic effects of alpelisib were substantially enhanced when combined with pharmacologic mTOR inhibition. These findings identify the alpha catalytic PI3K isoform as a unique therapeutic target in proneural GBM and suggest that pharmacological mTOR inhibition may sensitize GSCs to selective PI3Kα inhibition.
Detection of oriented fractal scaling components in anisotropic two-dimensional trajectories
Authors: Seleznov Ivan , Popov Anton , Kikuchi Kazuhei , Kolosova Elena , Kolomiiets Bohdan , Nakata Akio , Kaneko Miki , Kiyono Ken
Published: December 2020

We propose a novel class of mixed fluctuations with different orientations and fractal scaling features as a model for anisotropic two-dimensional (2D) trajectories hypothesized to appear in complex systems. Furthermore, we develop the oriented fractal scaling component analysis (OFSCA) to decompose such mixed fluctuations into the original orientation components. In the OFSCA, the original orientations are detected based on the principle that the original angles are orthogonal to the angles with the minimum and maximum scaling exponents of the mixed fluctuations. In our approach, the angle-dependent scaling properties are estimated using the Savitzky–Golay-filter-based detrended moving-average analysis (DMA), which has a higher detrending order than the conventional moving-average-filter-based DMA. To illustrate the OFSCA, we demonstrate that the numerically generated time-series of mixed fractional Gaussian noise (fGn) processes with non-orthogonal orientations and different scaling exponents is successfully decomposed into the original fGn components. We demonstrate the existence of oriented components in the 2D trajectories by applying OFSCA to real-world time-series, such as human postural fluctuations during standing and seismic ground acceleration during the great 2011 Tohoku-oki earthquake.
Gene expression network analysis provides potential targets against SARS-CoV-2
Authors: Hernández Cordero Ana I. , Li Xuan , Yang Chen Xi , Milne Stephen , Bossé Yohan , Joubert Philippe , Timens Wim , van den Berge Maarten , Nickle David , Hao Ke , Sin Don D.
Published: December 2020

Cell entry of SARS-CoV-2, the novel coronavirus causing COVID-19, is facilitated by host cell angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). We aimed to identify and characterize genes that are co-expressed with ACE2 and TMPRSS2, and to further explore their biological functions and potential as druggable targets. Using the gene expression profiles of 1,038 lung tissue samples, we performed a weighted gene correlation network analysis (WGCNA) to identify modules of co-expressed genes. We explored the biology of co-expressed genes using bioinformatics databases, and identified known drug-gene interactions. ACE2 was in a module of 681 co-expressed genes; 10 genes with moderate-high correlation with ACE2 (r > 0.3, FDR < 0.05) had known interactions with existing drug compounds. TMPRSS2 was in a module of 1,086 co-expressed genes; 31 of these genes were enriched in the gene ontology biologic process ‘receptor-mediated endocytosis’, and 52 TMPRSS2-correlated genes had known interactions with drug compounds. Dozens of genes are co-expressed with ACE2 and TMPRSS2, many of which have plausible links to COVID-19 pathophysiology. Many of the co-expressed genes are potentially targetable with existing drugs, which may accelerate the development of COVID-19 therapeutics.