bluuebunny/crossref_metadata_2025 huggingface dataset:
Length at maturity and relationship between weight and total length of five deep-sea fishes from the, Andaman and Nicobar Islands of India, North-eastern Indian Ocean
Authors: Sileesh Mullasseri , Kurup B. Madhusoodana , Korath Alphi
Published: June 2020

We have estimated the length at maturity and length-weight relationships for five fish species inhabiting the deep-sea from the Andaman and Nicobar Islands off the Indian coast between 295–650 m deep in a trawl survey carried out in March–April 2017. Hauls were carried out by a high-speed Demersal Trawl Crustacean Version trawl net and analysis was performed for a total of 832 specimens. Length at first maturity of the five deep-sea fish species ranged from 14.28–105.73 cm while length at 90% maturity was in the range 17.87–159.83 cm. The length at maturity of the fish are Alepocephalus bicolor (male = 66.09, female = 105.73), Bathyclupea hoskynii (m = 15.14, f = 14.15), Chlorophthalmus corniger (m = 17.54, f = 15.31), Neoepinnula orientalis (m = 20.76, f = 16.76), and Neoscopelus microchir (m = 14.28, f = 15.40). The b value in the length-weight relationship ranged from 0.69–2.60, i.e. Alepocephalus bicolor (m = 1.93, f = 1.62), Bathyclupea hoskynii (m = 3.5, f = 1.66), Chlorophthalmus corniger (m = 2.07, f = 1.56), Neoepinnula orientalis (m = 2.86, f = 2.46) and Neoscopelus microchir (m = 0.89, f = 0.49). Based on these results, the b value showed an allometric relationship with length for all species studied, because these species have a similar morphometry, i.e. a flattened back. Since they are primary or secondary consumers at the bottom of consumer food webs, their roles are as predators of small–medium prey and as prey of top predators of food web chains.
Parenting practices and intergenerational cycle of victimization in Peru
Authors: Scheid Caroline R. , Miller-Graff Laura E. , Guzmán Danice B.
Published: June 2020

Existing research has suggested children of caregivers with histories of exposure to trauma are at heightened risk for victimization, but few studies have explored potential mechanisms that explain this intergenerational transmission of risk. With data from peri-urban households in Lima, Peru (N= 402), this study analyzes parenting behaviors in the relation between caregivers’ trauma history and child victimization for children aged 4–17. Results indicated caregivers’ trauma history and negative parenting behaviors related to child victimization, and negative parenting behaviors mediated this relation. Positive parenting behaviors did not have significant direct effects and were not mediators of risk transmission. Parenting behaviors did not moderate the relation between caregiver and child victimization, suggesting parenting behaviors may not buffer or exacerbate intergenerational transmission. Post-hoc analyses revealed family type (e.g., single, cohabitating/married) exerted significant direct and moderating effects on child risk, interacting with positive parenting. Families with married/cohabitating caregivers reported overall lower levels of child victimization; however, the relation between positive parenting and victimization was slightly stronger for children in single-parent families. Results highlight potential pathways of the intergenerational cycle of victimization and suggest high-risk families in Peru may benefit from parenting supports, especially pertaining to remediation of negative parenting behaviors.
Learning and meta-learning of stochastic advection–diffusion–reaction systems from sparse measurements
Authors: CHEN XIAOLI , DUAN JINQIAO , KARNIADAKIS GEORGE EM
Published: June 2020

Physics-informed neural networks (PINNs) were recently proposed in [18] as an alternative way to solve partial differential equations (PDEs). A neural network (NN) represents the solution, while a PDE-induced NN is coupled to the solution NN, and all differential operators are treated using automatic differentiation. Here, we first employ the standard PINN and a stochastic version, sPINN, to solve forward and inverse problems governed by a non-linear advection–diffusion–reaction (ADR) equation, assuming we have some sparse measurements of the concentration field at random or pre-selected locations. Subsequently, we attempt to optimise the hyper-parameters of sPINN by using the Bayesian optimisation method (meta-learning) and compare the results with the empirically selected hyper-parameters of sPINN. In particular, for the first part in solving the inverse deterministic ADR, we assume that we only have a few high-fidelity measurements, whereas the rest of the data is of lower fidelity. Hence, the PINN is trained using a composite multi-fidelity network, first introduced in [12], that learns the correlations between the multi-fidelity data and predicts the unknown values of diffusivity, transport velocity and two reaction constants as well as the concentration field. For the stochastic ADR, we employ a Karhunen–Loève (KL) expansion to represent the stochastic diffusivity, and arbitrary polynomial chaos (aPC) to represent the stochastic solution. Correspondingly, we design multiple NNs to represent the mean of the solution and learn each aPC mode separately, whereas we employ a separate NN to represent the mean of diffusivity and another NN to learn all modes of the KL expansion. For the inverse problem, in addition to stochastic diffusivity and concentration fields, we also aim to obtain the (unknown) deterministic values of transport velocity and reaction constants. The available data correspond to 7spatial points for the diffusivity and 20 space–time points for the solution, both sampled 2000 times. We obtain good accuracy for the deterministic parameters of the order of 1–2% and excellent accuracy for the mean and variance of the stochastic fields, better than three digits of accuracy. In the second part, we consider the previous stochastic inverse problem, and we use Bayesian optimisation to find five hyper-parameters of sPINN, namely the width, depth and learning rate of two NNs for learning the modes. We obtain much deeper and wider optimal NNs compared to the manual tuning, leading to even better accuracy, i.e., errors less than 1% for the deterministic values, and about an order of magnitude less for the stochastic fields.
Optimisation of CT scan parameters to increase the accuracy of gross tumour volume identification in brain radiotherapy
Authors: Estak Kosar , Mohammadzadeh Mohammad , Gharehaghaji Nahideh , Mortezazadeh Tohid , Khatyal Rahim , Khezerloo Davood
Published: June 2020

Aim:

This study aimed to optimise computed tomography (CT) simulation scan parameters to increase the accuracy for gross tumour volume identification in brain radiotherapy. For this purpose, high-contrast scan protocols were assessed.

Materials and methods:

A CT accreditation phantom (ACR Gammex 464) was used to optimise brain CT scan parameters on a Toshiba Alexion 16-row multislice CT scanner. Dose, tube voltage, tube current–time and CT dose index (CTDI) were varied to create five image quality enhancement (IQE) protocols. They were assessed in terms of contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR) and noise level and compared with a standard clinical protocol. Finally, the ability of the selected protocols to identify low-contrast objects was examined based on a subjective method.

Results:

Among the five IQE protocols, the one with the highest tube current–time product (250 mA) and lowest tube voltage (100 kVp) showed higher CNR, while another with a tube current–time product of 150 mA and a tube voltage of 135 kVp had improved SNR and lower noise level compared to the standard protocol. In contouring low-contrast objects, the protocol with the highest milliampere and lowest peak kilovoltage exhibited the lowest error rate (1%) compared to the standard protocol (25%).

Findings:

CT image quality should be optimised using the high-dose parameters created in this study to provide better soft tissue contrast. This could lead to an accurate identification of gross tumour volume recognition in the planning of radiotherapy treatment.
GAMES AND HEREDITARY BAIRENESS IN HYPERSPACES AND SPACES OF PROBABILITY MEASURES
Authors: Krupski Mikołaj
Published: June 2020

We establish that the existence of a winning strategy in certain topological games, closely related to a strong game of Choquet, played in a topological space $X$ and its hyperspace $K(X)$ of all nonempty compact subsets of $X$ equipped with the Vietoris topology, is equivalent for one of the players. For a separable metrizable space $X$, we identify a game-theoretic condition equivalent to $K(X)$ being hereditarily Baire. It implies quite easily a recent result of Gartside, Medini and Zdomskyy that characterizes hereditary Baire property of hyperspaces $K(X)$ over separable metrizable spaces $X$ via the Menger property of the remainder of a compactification of $X$. Subsequently, we use topological games to study hereditary Baire property in spaces of probability measures and in hyperspaces over filters on natural numbers. To this end, we introduce a notion of strong $P$-filter ${\mathcal{F}}$ and prove that it is equivalent to $K({\mathcal{F}})$ being hereditarily Baire. We also show that if $X$ is separable metrizable and $K(X)$ is hereditarily Baire, then the space $P_{r}(X)$ of Borel probability Radon measures on $X$ is hereditarily Baire too. It follows that there exists (in ZFC) a separable metrizable space $X$, which is not completely metrizable with $P_{r}(X)$ hereditarily Baire. As far as we know, this is the first example of this kind.
One-upmanship and putdowns: the aggressive use of interaction rituals in face-to-face diplomacy
Authors: Wong Seanon S.
Published: June 2020

When leaders meet in person, they perform a wide range of interaction rituals. They dress for the occasion, greet each other and shake hands, exchange pleasantries and gifts, arrive at the meeting venue and have themselves seated according to protocol, and so on. What do they make of the performance of such rituals? In this paper, I argue that leaders often take advantage of or outright flout what the sociologist Erving Goffman calls the prevailing ‘ceremonial idiom’ of an interaction – that is the intersubjective understanding they share on what rituals to perform and how to perform them – to realize a number of political and personal objectives, with larger international consequences. The ‘ceremonial idiom’ is deliberately transgressed and a counterpart's ‘face’ threatened – overtly but more often subtly – to achieve what are commonly known as ‘one-upmanship’ and ‘putdowns’ in interpersonal contact. Empirically, I demonstrate my argument with over two dozen episodes of face-to-face diplomacy across six categories of interaction rituals: the identity of leaders, gestural, spatial–physical, task-embedded, linguistic, and communication rules. I also outline several directions for future research.
Developmental Origins of Health and Disease: Impact of environmental dust exposure in modulating microbiome and its association with non-communicable diseases
Authors: Ooi Delicia Shu-Qin , Tan Cheryl Pei-Ting , Tay Michelle Jia-Yu , Ong Siong Gim , Tham Elizabeth Huiwen , Siah Kewin Tien Ho , Eriksson Johan Gunnar , Godfrey Keith M. , Shek Lynette Pei-Chi , Loo Evelyn Xiu-Ling
Published: June 2020

Non-communicable diseases (NCDs) including obesity, diabetes, and allergy are chronic, multi-factorial conditions that are affected by both genetic and environmental factors. Over the last decade, the microbiome has emerged as a possible contributor to the pathogenesis of NCDs. Microbiome profiles were altered in patients with NCDs, and shift in microbial communities was associated with improvement in these health conditions. Since the genetic component of these diseases cannot be altered, the ability to manipulate the microbiome holds great promise for design of novel therapies in the prevention and treatment of NCDs. Together, the Developmental Origins of Health and Disease concept and the microbial hypothesis propose that early life exposure to environmental stimuli will alter the development and composition of the human microbiome, resulting in health consequences. Recent studies indicated that the environment we are exposed to in early life is instrumental in shaping robust immune development, possibly through modulation of the human microbiome (skin, airway, and gut). Despite much research into human microbiome, the origin of their constituent microbiota remains unclear. Dust (also known as particulate matter) is a key determinant of poor air quality in the modern urban environment. It is ubiquitous and serves as a major source and reservoir of microbial communities that modulates the human microbiome, contributing to health and disease. There are evidence that reported significant associations between environmental dust and NCDs. In this review, we will focus on the impact of dust exposure in shaping the human microbiome and its possible contribution to the development of NCDs.
Comparative Analysis of the Vlasiator Simulations and MMS Observations of Multiple X‐Line Reconnection and Flux Transfer Events
Authors: Akhavan‐Tafti M. , Palmroth M. , Slavin J. A. , Battarbee M. , Ganse U. , Grandin M. , Le G. , Gershman D. J. , Eastwood J. P. , Stawarz J. E.
Published: June 2020

The Vlasiator hybrid‐Vlasov code was developed to investigate global magnetospheric dynamics at ion‐kinetic scales. Here we focus on the role of magnetic reconnection in the formation and evolution of magnetic islands at the low‐latitude magnetopause, under southward interplanetary magnetic field conditions. The simulation results indicate that (1) the magnetic reconnection ion kinetics, including the Earthward pointing Larmor electric field on the magnetospheric side of an X‐point and anisotropic ion distributions, are well‐captured by Vlasiator, thus enabling the study of reconnection‐driven magnetic island evolution processes, (2) magnetic islands evolve due to continuous reconnection at adjacent X‐points, “coalescence” which refers to the merging of neighboring islands to create a larger island, “erosion” during which an island loses magnetic flux due to reconnection, and “division” which involves the splitting of an island into smaller islands, and (3) continuous reconnection at adjacent X‐points is the dominant source of magnetic flux and plasma to the outer layers of magnetic islands resulting in cross‐sectional growth rates up to + 0.3 RE2/min. The simulation results are compared to the Magnetospheric Multiscale (MMS) measurements of a chain of ion‐scale flux transfer events (FTEs) sandwiched between two dominant X‐lines. The MMS measurements similarly reveal (1) anisotropic ion populations and (2) normalized reconnection rate ~0.18, in agreement with theory and the Vlasiator predictions. Based on the simulation results and the MMS measurements, it is estimated that the observed ion‐scale FTEs may grow Earth‐sized within ~10 min, which is comparable to the average transport time for FTEs formed in the subsolar region to the high‐latitude magnetopause. Future simulations shall revisit reconnection‐driven island evolution processes with improved spatial resolutions.
Tropical Cyclone‐Induced Gravity Wave Perturbations in the Upper Atmosphere: GITM‐R Simulations
Authors: Zhao Yuxin , Deng Yue , Wang Jing‐Song , Zhang Shun‐Rong , Lin Cissi Y.
Published: June 2020

The tropical cyclone (TC)‐induced concentric gravity waves (CGWs) are capable of propagating upward from convective sources in the troposphere to the upper atmosphere and creating concentric traveling ionospheric disturbances (CTIDs). To examine the CGWs propagation, we implement tropical cyclone‐induced CGWs into the lower boundary of global ionosphere‐thermosphere model with local‐grid refinement (GITM‐R) and simulate the influence of CGWs on the ionosphere and thermosphere. GITM‐R is a three‐dimensional non‐hydrostatic general circulation model for the upper atmosphere with the local‐grid refinement module to enhance the resolution at the location of interest. In this study, CGWs induced by the typhoon Meranti in 2016 have been simulated. Information of the TC shape and moving trails is obtained from the TC best‐track dataset, and the gravity wave patterns are specified at the lower boundary of GITM‐R (100 km altitude). The horizontal wavelength and phase velocity of wave perturbation at the lower boundary are specified to be consistent with the TEC observations. The simulation reveals a clear evolution of CTIDs, which shows reasonable agreement with the GPS‐TEC observations. This is the first time the typhoon‐driven TEC perturbation has been simulated in a general circulation model. To further examine the dependence of the CTIDs on the wavelength and frequency of the gravity wave perturbation at the lower boundary, different waveforms have been tested as well. The magnitude of CTIDs has a negative correlation with the period but a positive correlation with the wavelength when the horizontal phase velocities are sufficiently fast against the critical‐level absorption.
Inversions of Estuarine Circulation Are Frequent in a Weakly Tidal Estuary With Variable Wind Forcing and Seaward Salinity Fluctuations
Authors: Lange Xaver , Klingbeil Knut , Burchard Hans
Published: June 2020

The hydrodynamics in estuaries is mainly governed by the competition between a horizontal density gradient, friction, and wind stress. The sensitivity of the estuarine exchange flow to the wind stress increases in the absence of tides, which is investigated here using the example of the weakly tidal Warnow river estuary in the southwestern Baltic Sea—the mouth of which is characterized by strongly varying salinities of 8 to 20 g kg−1. The interaction between a volatile salinity gradient and along‐estuary wind forcing is found to cause temporary inversions of the estuarine circulation. Despite the highly dynamic conditions, the applicability of recent theories for isohaline mixing, using the framework of Total Exchange Flow, and the strength of the exchange flow, using a non‐dimensional parameter space, could be confirmed. By analyzing salinity fluxes at the mouth of the estuary, a mixing completeness of 84% was calculated for the estuary. Furthermore, inversion of estuarine circulation was typically found for a local Wedderburn number (ratio of non‐dimensional wind stress to non‐dimensional horizontal density gradient) exceeding 0.33, indicating a high sensitivity to along‐estuary wind.
Li Partitioning Into Coccoliths of Emiliania huxleyi: Evaluating the General Role of “Vital Effects” in Explaining Element Partitioning in Biogenic Carbonates
Authors: Langer Gerald , Sadekov Aleksey , Greaves Mervyn , Nehrke Gernot , Probert Ian , Misra Sambuddha , Thoms Silke
Published: June 2020

Emiliania huxleyi cells were grown in artificial seawater of different Li and Ca concentrations and coccolith Li/Ca ratios determined. Coccolith Li/Ca ratios were positively correlated to seawater Li/Ca ratios only if the seawater Li concentration was changed, not if the seawater Ca concentration was changed. This Li partitioning pattern of E. huxleyi was previously also observed in the benthic foraminifer Amphistegina lessonii and inorganically precipitated calcite. We argue that Li partitioning in both E. huxleyi and A. lessonii is dominated by a coupled transmembrane transport of Li and Ca from seawater to the site of calcification. We present a refined version of a recently proposed transmembrane transport model for Li and Ca. The model assumes that Li and Ca enter the cell via Ca channels, the Li flux being dependent on the Ca flux. While the original model features a linear function to describe the experimental data, our refined version uses a power function, changing the stoichiometry of Li and Ca. The version presented here accurately predicts the observed dependence of DLi on seawater Li/Ca ratios. Our data demonstrate that minor element partitioning in calcifying organisms is partly mediated by biological processes even if the partitioning behavior of the calcifying organism is indistinguishable from that of inorganically precipitated calcium carbonate.
Characteristics of Minor Ions and Electrons in Flux Transfer Events Observed by the Magnetospheric Multiscale Mission
Authors: Petrinec S. M. , Burch J. L. , Chandler M. , Farrugia C. J. , Fuselier S. A. , Giles B. L. , Gomez R. G. , Mukherjee J. , Paterson W. R. , Russell C. T. , Sibeck D. G. , Strangeway R. J. , Torbert R. B. , Trattner K. J. , Vines S. K. , Zhao C.
Published: June 2020

In this study, the ion composition of flux transfer events (FTEs) observed within the magnetosheath proper is examined. These FTEs were observed just upstream of the Earth's postnoon magnetopause by the National Aeronautics and Space Administration (NASA) Magnetospheric Multiscale (MMS) spacecraft constellation. The minor ion characteristics are described using energy spectrograms, flux distributions, and ion moments as the constellation encountered each FTE. In conjunction with electron data and magnetic field observations, such observations provide important contextual information on the formation, topologies, and evolution of FTEs. In particular, minor ions, when combined with the field‐aligned streaming of electrons, are reliable indicators of FTE topology. The observations are also placed (i) in context of the solar wind magnetic field configuration, (ii) the connection of the sampled flux tube to the ionosphere, and (iii) the location relative to the modeled reconnection line at the magnetopause. While protons and alpha particles were often depleted within the FTEs relative to the surrounding magnetosheath plasma, the He+ and O+ populations showed clear enhancements either near the center or near the edges of the FTE, and the bulk plasma flow directions are consistent with magnetic reconnection northward of the spacecraft and convection from the dayside toward the flank magnetopause.
Independent influences of maternal obesity and fetal sex on maternal cardiovascular adaptation to pregnancy: a prospective cohort study
Authors: Teulings Noor E. W. D. , Wood Angela M. , Sovio Ulla , Ozanne Susan E. , Smith Gordon C. S. , Aiken Catherine E.
Published: June 2020

Background/Objectives

Successful pregnancy requires the de novo creation of low-resistance utero-placental and feto-placental circulations and incomplete remodeling of this vasculature can lead to maternal or fetal compromise. Maternal BMI and fetal sex are known to influence vascular compliance and placental development, but it is unknown if these are independent or synergistic effects. Here we aim to investigate the impact of maternal obesity, fetal sex, and any interaction thereof on maternal cardiovascular adaptation to pregnancy, by assessing the physiological drop of uterine artery doppler pulsatility (UtA-PI) and umbilical artery doppler pulsatility index (UA-PI) over gestation.

Subjects/Methods

Nulliparous women with a singleton pregnancy participating in a prospective cohort study (n = 4212) underwent serial UtA-PI and UA-PI measurements at 20-, 28- and 36-weeks gestation. Linear mixed regression models were employed to investigate the influence of maternal BMI, fetal sex and interactions thereof on the magnitude of change in UtA-PI and UA-PI.

Results

Throughout gestation, UtA-PI was higher for male fetuses and UA-PI was higher for female fetuses. The physiological drop of UtA-PI was significantly smaller in overweight (change −24.3% [95%CI −22.3, −26.2]) and obese women (change −21.3% [−18.3, −24.3]), compared to normal-weight women (change −25.7% [−24.3, −27.0]) but did not differ by fetal sex. The physiological drop in UA-PI was greater for female than male fetuses (–32.5% [−31.5, −33.5] vs. −30.7% [−29.8, −31.7]) but did not differ by maternal BMI. No interactions between maternal BMI and fetal sex were found.

Conclusions

Maternal cardiovascular adaptation to pregnancy is independently associated with maternal BMI and fetal sex. Our results imply sexual dimorphism in both maternal cardiovascular adaptation and feto-placental resistance.
Metformin effectively treats Tsc1 deletion-caused kidney pathology by upregulating AMPK phosphorylation
Authors: Fang Yili , Li Fang , Qi Chenyang , Mao Xing , Wang Feng , Zhao Zhonghua , Chen Jian-Kang , Zhang Zhigang , Wu Huijuan
Published: June 2020

Tuberous sclerosis complex (TSC) is characterized by hamartomatous lesions in multiple organs, with most patients developing polycystic kidney disease and leading to a decline of renal function. TSC is caused by loss-of-function mutations in either Tsc1 or Tsc2 gene, but currently, there is no effective treatment for aberrant kidney growth in TSC patients. By generating a renal proximal tubule-specific Tsc1 gene-knockout (Tsc1ptKO) mouse model, we observed that Tsc1ptKO mice developed aberrantly enlarged kidneys primarily due to hypertrophy and proliferation of proximal tubule cells, along with some cystogenesis, interstitial inflammation, and fibrosis. Mechanistic studies revealed inhibition of AMP-activated protein kinase (AMPK) phosphorylation at Thr-172 and activation of Akt phosphorylation at Ser-473 and Thr-308. We therefore treated Tsc1ptKO mice with the AMPK activator, metformin, by daily intraperitoneal injection. Our results indicated that metformin increased the AMPK phosphorylation, but decreased the Akt phosphorylation. These signaling modulations resulted in inhibition of proliferation and induction of apoptosis in the renal proximal tubule cells of Tsc1ptKO mice. Importantly, metformin treatment effectively prevented aberrant kidney enlargement and cyst growth, inhibited inflammatory response, attenuated interstitial fibrosis, and protected renal function. The effects of metformin were further confirmed by in vitro experiments. In conclusion, this study indicates a potential therapeutic effect of metformin on Tsc1 deletion-induced kidney pathology, although currently metformin is primarily prescribed to treat patients with type 2 diabetes.
Author Correction: Mendelian neurodegenerative disease genes involved in autophagy
Authors: Stamatakou Eleanna , Wrobel Lidia , Hill Sandra Malmgren , Puri Claudia , Son Sung Min , Fujimaki Motoki , Zhu Ye , Siddiqi Farah , Fernandez-Estevez Marian , Manni Marco M. , Park So Jung , Villeneuve Julien , Rubinsztein David Chaim
Published: June 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Structure and mechanism of DNA delivery of a gene transfer agent
Authors: Bárdy Pavol , Füzik Tibor , Hrebík Dominik , Pantůček Roman , Thomas Beatty J. , Plevka Pavel
Published: June 2020

Alphaproteobacteria, which are the most abundant microorganisms of temperate oceans, produce phage-like particles called gene transfer agents (GTAs) that mediate lateral gene exchange. However, the mechanism by which GTAs deliver DNA into cells is unknown. Here we present the structure of the GTA of Rhodobacter capsulatus (RcGTA) and describe the conformational changes required for its DNA ejection. The structure of RcGTA resembles that of a tailed phage, but it has an oblate head shortened in the direction of the tail axis, which limits its packaging capacity to less than 4,500 base pairs of linear double-stranded DNA. The tail channel of RcGTA contains a trimer of proteins that possess features of both tape measure proteins of long-tailed phages from the family Siphoviridae and tail needle proteins of short-tailed phages from the family Podoviridae. The opening of a constriction within the RcGTA baseplate enables the ejection of DNA into bacterial periplasm.
DG–CA3 circuitry mediates hippocampal representations of latent information
Authors: Keinath Alexandra T. , Nieto-Posadas Andrés , Robinson Jennifer C. , Brandon Mark P.
Published: June 2020

Survival in complex environments necessitates a flexible navigation system that incorporates memory of recent behavior and associations. Yet, how the hippocampal spatial circuit represents latent information independent of sensory inputs and future goals has not been determined. To address this, we image the activity of large ensembles in subregion CA1 via wide-field fluorescent microscopy during a novel behavioral paradigm. Our results demonstrate that latent information is represented through reliable firing rate changes during unconstrained navigation. We then hypothesize that the representation of latent information in CA1 is mediated by pattern separation/completion processes instantiated upstream within the dentate gyrus (DG) and CA3 subregions. Indeed, CA3 ensemble recordings reveal an analogous code for latent information. Moreover, selective chemogenetic inactivation of DG–CA3 circuitry completely and reversibly abolishes the CA1 representation of latent information. These results reveal a causal and specific role of DG–CA3 circuitry in the maintenance of latent information within the hippocampus.
Dual Role of WISP1 in maintaining glioma stem cells and tumor-supportive macrophages in glioblastoma
Authors: Tao Weiwei , Chu Chengwei , Zhou Wenchao , Huang Zhi , Zhai Kui , Fang Xiaoguang , Huang Qian , Zhang Aili , Wang Xiuxing , Yu Xingjiang , Huang Haidong , Wu Qiulian , Sloan Andrew E. , Yu Jennifer S. , Li Xiaoxia , Stark George R. , Rich Jeremy N. , Bao Shideng
Published: June 2020

The interplay between glioma stem cells (GSCs) and the tumor microenvironment plays crucial roles in promoting malignant growth of glioblastoma (GBM), the most lethal brain tumor. However, the molecular mechanisms underlying this crosstalk are incompletely understood. Here, we show that GSCs secrete the Wnt‐induced signaling protein 1 (WISP1) to facilitate a pro-tumor microenvironment by promoting the survival of both GSCs and tumor-associated macrophages (TAMs). WISP1 is preferentially expressed and secreted by GSCs. Silencing WISP1 markedly disrupts GSC maintenance, reduces tumor-supportive TAMs (M2), and potently inhibits GBM growth. WISP1 signals through Integrin α6β1-Akt to maintain GSCs by an autocrine mechanism and M2 TAMs through a paracrine manner. Importantly, inhibition of Wnt/β-catenin-WISP1 signaling by carnosic acid (CA) suppresses GBM tumor growth. Collectively, these data demonstrate that WISP1 plays critical roles in maintaining GSCs and tumor-supportive TAMs in GBM, indicating that targeting Wnt/β-catenin-WISP1 signaling may effectively improve GBM treatment and the patient survival.
ORIGIN: a novel and compact Laser Desorption – Mass Spectrometry system for sensitive in situ detection of amino acids on extraterrestrial surfaces
Authors: Ligterink Niels F. W. , Grimaudo Valentine , Moreno-García Pavel , Lukmanov Rustam , Tulej Marek , Leya Ingo , Lindner Robert , Wurz Peter , Cockell Charles S. , Ehrenfreund Pascale , Riedo Andreas
Published: June 2020

For the last four decades space exploration missions have searched for molecular life on planetary surfaces beyond Earth. Often pyrolysis gas chromatography mass spectrometry has been used as payload on such space exploration missions. These instruments have relatively low detection sensitivity and their measurements are often undermined by the presence of chloride salts and minerals. Currently, ocean worlds in the outer Solar System, such as the icy moons Europa and Enceladus, represent potentially habitable environments and are therefore prime targets for the search for biosignatures. For future space exploration missions, novel measurement concepts, capable of detecting low concentrations of biomolecules with significantly improved sensitivity and specificity are required. Here we report on a novel analytical technique for the detection of extremely low concentrations of amino acids using ORIGIN, a compact and lightweight laser desorption ionization – mass spectrometer designed and developed for in situ space exploration missions. The identified unique mass fragmentation patterns of amino acids coupled to a multi-position laser scan, allows for a robust identification and quantification of amino acids. With a detection limit of a few fmol mm−2, and the possibility for sub-fmol detection sensitivity, this measurement technique excels current space exploration systems by three orders of magnitude. Moreover, our detection method is not affected by chemical alterations through surface minerals and/or salts, such as NaCl that is expected to be present at the percent level on ocean worlds. Our results demonstrate that ORIGIN is a promising instrument for the detection of signatures of life and ready for upcoming space missions, such as the Europa Lander.
Hyperpolarized [1,4-13C]fumarate imaging detects microvascular complications and hypoxia mediated cell death in diabetic nephropathy
Authors: Laustsen Christoffer , Nielsen Per Mose , Qi Haiyun , Løbner Mette Hadberg , Palmfeldt Johan , Bertelsen Lotte Bonde
Published: June 2020

Today, there is a general lack of prognostic biomarkers for development of renal disease and in particular diabetic nephropathy. Increased glycolytic activity, lactate accumulation and altered mitochondrial oxygen utilization are hallmarks of diabetic kidney disease. Fumarate hydratase activity has been linked to mitochondrial dysfunction as well as activation of the hypoxia inducible factor, induction of apoptosis and necrosis. Here, we investigate fumarate hydratase activity in biofluids in combination with the molecular imaging probe, hyperpolarized [1,4-13C2]fumarate, to identify the early changes associated with hemodynamics and cell death in a streptozotocin rat model of type 1 diabetes. We found a significantly altered hemodynamic signature of [1,4-13C2]fumarate in the diabetic kidneys as well as an systemic increased metabolic conversion of fumarate-to-malate, indicative of increased cell death associated with progression of diabetes, while little to no renal specific conversion was observed. This suggest apoptosis as the main cause of cell death in the diabetic kidney. This is likely resulting from an increased reactive oxygen species production following uncoupling of the electron transport chain at complex II. The mechanism coupling the enzyme leakage and apoptotic phenotype is hypoxia inducible factor independent and seemingly functions as a protective mechanism in the kidney cells.
Using Accelerated Molecular Dynamics Simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein
Authors: Valente Renan Patrick da Penha , Souza Rafael Conceição de , de Medeiros Muniz Gabriela , Ferreira João Elias Vidueira , de Miranda Ricardo Morais , e Lima Anderson Henrique Lima , Vianez Junior João Lídio da Silva Gonçalves
Published: June 2020

The envelope (E) protein is an important target for antibodies in flavivirus. Literature reports that the mutation T198F, located at the domain I-II hinge of the E protein, regulates viral breathing and increases the accessibility of a distal cryptic epitope located on the fusion loop, having a direct impact in the neutralization of West Nile virus (WNV). Our study aimed to describe, using accelerated molecular dynamics simulations, the effects of the T198F mutation in the flexibility of the E protein of WNV and to elucidate the mechanism that regulates epitope accessibility. The simulation results revealed that the mutation favors the formation of alternative hydrogen bonds, hampering the bending movement between domains I and II. We hypothesized that this is the mechanism by which the T198F mutation, located at the middle of the protein, locks the distal cryptc epitope near a single preferred conformation, rendering it more prone to recognition by antibodies.
Human ZKSCAN3 and Drosophila M1BP are functionally homologous transcription factors in autophagy regulation
Authors: Barthez Marine , Poplineau Mathilde , Elrefaey Marwa , Caruso Nathalie , Graba Yacine , Saurin Andrew J.
Published: June 2020

Autophagy is an essential cellular process that maintains homeostasis by recycling damaged organelles and nutrients during development and cellular stress. ZKSCAN3 is the sole identified master transcriptional repressor of autophagy in human cell lines. How ZKSCAN3 achieves autophagy repression at the mechanistic or organismal level however still remains to be elucidated. Furthermore, Zkscan3 knockout mice display no discernable autophagy-related phenotypes, suggesting that there may be substantial differences in the regulation of autophagy between normal tissues and tumor cell lines. Here, we demonstrate that vertebrate ZKSCAN3 and Drosophila M1BP are functionally homologous transcription factors in autophagy repression. Expression of ZKSCAN3 in Drosophila prevents premature autophagy onset due to loss of M1BP function and conversely, M1BP expression in human cells can prevent starvation-induced autophagy due to loss of nuclear ZKSCAN3 function. In Drosophila ZKSCAN3 binds genome-wide to sequences targeted by M1BP and transcriptionally regulates the majority of M1BP-controlled genes, demonstrating the evolutionary conservation of the transcriptional repression of autophagy. This study thus  allows the potential for transitioning the mechanisms, gene targets and plethora metabolic processes controlled by M1BP onto ZKSCAN3 and opens up Drosophila as a tool in studying the function of ZKSCAN3 in autophagy and tumourigenesis.
Impediometric Electrochemical Sensor Based on The Inspiration of Carnation Italian Ringspot Virus Structure to Detect an Attommolar of miR
Authors: Ghazizadeh E. , Moosavifard Seyyed Ebrahim , Daneshmand Negin , Kaverlavani Saeid kamari
Published: June 2020

Electrochemical sensors are the tools to detect the accurate and sensitive miRs. There is the challenge to increase the power and sensitivity of the surface for the electrochemical sensor. We design a virus-like hallow structure of cuco2o4 that it holds the large amounts of p19 protein by mimicking of inherent virus (Carnation italian ringspot virus) to detect 21mir with the limit of detection (LOD = 1aM). The electrochemical measurements are performed between the potentials at −0.3 V and +0.3 V with 1 mM [Fe(CN)6] −3/−4. After dropping the cuco2o4 on the SCPE (screen carbon printed electrode), the sensor is turned on due to the high electrochemical properties. Then, p19 proteins move into the hallow structure and inhibit the exchange of electrochemical reactions between the shells and the sensor is turned off. Then, adding the duplexes of RNA/miRs cause to increase the electrochemical property of p19 due to the change of p19 conformation and the system is turned on, again. So, for the first time, a virus-like hallow structure has been used to detect the 21miR in the human serum, MCF-7, Hella cells, with high sensitivity, specificity, and reproducibility in few minutes.
Discordance for genotypic sex in phenotypic female Atlantic salmon (Salmo salar) is related to a reduced sdY copy number
Authors: Brown Morgan S. , Evans Brad S. , Afonso Luis O. B.
Published: June 2020

The master sex determinant in rainbow trout (Oncorhynchus mykiss), sexually dimorphic on the Y chromosome (sdY), is strongly but not perfectly associated with male phenotype in several other species from the family Salmonidae. Currently, the cause and implications of discordance forsdY-predicted genotypic sex and phenotypic sex in these species is unclear. Using an established multiplex PCR test for exons 2 and 3 ofsdY, we demonstrated thatsdY-predicted genotypic sex was discordant with histologically evidenced phenotypic sex in 4% of 176 Tasmanian Atlantic salmon. All discordant individuals were phenotypic females presenting a male genotype. Using real-time qPCR assays that we developed and validated for exons 2, 3 and 4 ofsdY, all genotype-phenotype discordant females were confirmed to possesssdY, albeit at a reduced number of copies when compared to phenotypic males. The real-time qPCR assays also demonstrated reduced levels ofsdYin 30% of phenotypic females that the established multiplex PCR-based test indicated to be devoid ofsdY. These findings suggestsdYmay be reduced in copy number or mosaicked in the genomic DNA ofsdY-positive phenotypic female Atlantic salmon and highlight the importance of understanding the effects of reducedsdYcopies on the development of phenotypic sex.
Dynamic K-edge Subtraction Fluoroscopy at a Compact Inverse-Compton Synchrotron X-ray Source
Authors: Kulpe Stephanie , Dierolf Martin , Günther Benedikt , Brantl Johannes , Busse Madleen , Achterhold Klaus , Gleich Bernhard , Pfeiffer Franz , Pfeiffer Daniela
Published: June 2020

X-ray fluoroscopy is a commonly applied diagnostic tool for morphological and functional evaluation of the intestine in clinical routine. Acquisition of repetitive X-ray images following oral or rectal application of iodine contrast agent visualizes the time dependent distribution of the contrast medium, and helps to detect for example leakages, tumors or functional disorders. However, movements of the intestine and air trapped inside usually prevent temporal subtraction imaging to be applied to fluoroscopy of the gastrointestinal tract. K-edge subtraction (KES) imaging would enable subtraction fluoroscopy because it allows for imaging of moving organs with little artefacts. Although KES imaging is a well established technique at synchrotron sources, this imaging method is not applied in clinical routine as it relies on brilliant synchrotron radiation. Recently emerging compact synchrotron X-ray sources could provide a quasi-monochromatic, high-flux X-ray beam and allow for the application of KES in a laboratory environment. Here, we present a filter-based dynamic KES approach at the Munich Compact Light Source (MuCLS), the first user-dedicated installation of a compact synchrotron X-ray source worldwide. Compared to conventional temporal subtraction X-ray radiography, our approach increases the contrast while reducing the generated image artefacts.
Simple Aesthetic Sense and Addiction Emerge in Neural Relations of Cost-Benefit Decision in Foraging
Authors: Gribkova Ekaterina D. , Catanho Marianne , Gillette Rhanor
Published: June 2020

A rudimentary aesthetic sense is found in the stimulus valuations and cost-benefit decisions made by primitive generalist foragers. These are based on factors governing personal economic decisions: incentive, appetite, and learning. We find that the addictive process is an extreme expression of aesthetic dynamics. An interactive, agent-based model, ASIMOV, reproduces a simple aesthetic sense from known neural relations of cost-benefit decision in foraging. In the presence of very high reward, an addiction-like process emerges. A drug-like prey provides extreme reward with no nutritive value, initiating high selectivity and prolonged cravings for drug through reward learning. Varying reward experience, caused by homeostatic changes in the neural circuitry of reward, further establishes the course of addiction, consisting of desensitization, withdrawal, resensitization, and associated changes in nutritional choice and pain sensitivity. These observations are consistent with the early evolution of addiction mechanisms in simple generalist foragers as an aesthetic sense for evaluating prey. ASIMOV is accessible to inspection, modification, and experiment, is adaptable as an educational tool, and provides insight on the possible coevolutionary origins of aesthetics and the addiction process.
α-synuclein overexpression in the retina leads to vision impairment and degeneration of dopaminergic amacrine cells
Authors: Marrocco Elena , Indrieri Alessia , Esposito Federica , Tarallo Valeria , Carboncino Anna , Alvino Filomena Grazia , De Falco Sandro , Franco Brunella , De Risi Maria , De Leonibus Elvira
Published: June 2020

The presence of α-synuclein aggregates in the retina of Parkinson’s disease patients has been associated with vision impairment. In this study we sought to determine the effects of α-synuclein overexpression on the survival and function of dopaminergic amacrine cells (DACs) in the retina. Adult mice were intravitreally injected with an adeno-associated viral (AAV) vector to overexpress human wild-type α-synuclein in the inner retina. Before and after systemic injections of levodopa (L-DOPA), retinal responses and visual acuity-driven behavior were measured by electroretinography (ERG) and a water maze task, respectively. Amacrine cells and ganglion cells were counted at different time points after the injection. α-synuclein overexpression led to an early loss of DACs associated with a decrease of light-adapted ERG responses and visual acuity that could be rescued by systemic injections of L-DOPA. The data show that α-synuclein overexpression affects dopamine neurons in the retina. The approach provides a novel accessible method to model the underlying mechanisms implicated in the pathogenesis of synucleinopathies and for testing novel treatments.
Vestibular Aging Process from 3D Physiological Imaging of the Membranous Labyrinth
Authors: Tanioka Hisaya , Tanioka Sayaka , Kaga Kimitaka
Published: June 2020

There is no three-dimensional (3D) technique to study the microanatomical structures of thein vivo3D vestibular membranous labyrinth. Recent two MRI methods using a contrast agent can only depict the low-resolution imaging of endolymphatic hydrops. Therefore, we provide the new precise volume rendering algorithms to create thein vivo3D vestibular membranous labyrinth images from high-resolution temporal bone low-dose CT data. We also ascertain whether the created 3D microstructure images are reliable in anatomical findings. Secondary, we will analyze the age-related changes of the vestibular membranous labyrinth. These created 3D membranous vestibular images were almost consistent with the appearance, dimensions, areas, and angles from those acquired in previous histological works. The age-related image changes showed the enlarged saccule in females, the enlarged utricle in males, and the dilated tendency of the lateral semicircular duct. These results may correlate to the findings of the previous physiological works on cervical and ocular vestibular evoked myogenic potentials, and gait studies. The age-related balance disorders may be associated with the enlargement of each membranous organ in the vestibule. This new imaging technique now enables visualizing microanatomical changes in thein vivomembranous vestibulum, and these created 3D images may suggest physiological information.
Joint Longitudinal Low Calcium High Phosphorus Trajectory Associates with Accelerated Progression, Acute Coronary Syndrome and Mortality in Chronic Kidney Disease
Authors: Ting I-Wen , Yeh Hung-Chieh , Huang Han-Chun , Chiang Hsiu-Yin , Chu Pei-Lun , Kuo Chin-Chi
Published: June 2020

The effects of long-term disturbance of the mineral metabolism on patients with chronic kidney disease (CKD) are unclear. We investigated whether the longitudinal Ca-P (joint calcium and phosphorus) trajectories are associated with incident end-stage renal disease (ESRD), acute coronary syndrome (ACS), and all-cause mortality in patients with CKD. We conducted a prospective cohort study by using data from a 13-year multidisciplinary pre-ESRD care registry. The final study population consisted of 4,237 CKD patients aged 20–90 years with data gathered from 2003 to 2015. Individuals’ Ca-P trajectories were defined using group-based multi-trajectory modeling into three distinct patterns: reference, moderately abnormal, and severely abnormal. Times to ESRD, ACS, and death were analyzed using multiple Cox regression. Compared with those with a “reference” Ca-P trajectory, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) for incidental ESRD were 5.92 (4.71–7.44) and 15.20 (11.85–19.50) for “moderately abnormal” and “severely abnormal” Ca-P trajectories, respectively. The corresponding aHRs for ACS were 1.94 (1.49–2.52) and 3.18 (2.30–4.39), and for all-cause mortality, they were 1.88 (1.64–2.16) and 2.46 (2.05–2.96) for “moderately abnormal” and “severely abnormal” Ca-P trajectories, respectively. For outcomes of progression to ESRD, the detrimental effects of abnormal Ca-P trajectories were more substantial in patients with CKD stage 3 than those with CKD stage 4 or 5 (p-value for interaction < 0.001). Future studies should validate reliable longitudinal cut-offs of serum phosphorus and consider the “lowering phosphorus— the lower the better, the earlier the better” approach to phosphorus control in CKD.