bluuebunny/crossref_metadata_2025 huggingface dataset:
Plexin-B2 orchestrates collective stem cell dynamics via actomyosin contractility, cytoskeletal tension and adhesion
Authors: Junqueira Alves Chrystian , Dariolli Rafael , Haydak Jonathan , Kang Sangjo , Hannah Theodore , Wiener Robert J. , DeFronzo Stefanie , Tejero Rut , Gusella Gabriele L. , Ramakrishnan Aarthi , Alves Dias Rodrigo , Wojcinski Alexandre , Kesari Santosh , Shen Li , Sobie Eric A. , Rodrigues Furtado de Mendonça José Paulo , Azeloglu Evren U. , Zou Hongyan , Friedel Roland H.
Published: October 2021

During morphogenesis, molecular mechanisms that orchestrate biomechanical dynamics across cells remain unclear. Here, we show a role of guidance receptor Plexin-B2 in organizing actomyosin network and adhesion complexes during multicellular development of human embryonic stem cells and neuroprogenitor cells. Plexin-B2 manipulations affect actomyosin contractility, leading to changes in cell stiffness and cytoskeletal tension, as well as cell-cell and cell-matrix adhesion. We have delineated the functional domains of Plexin-B2, RAP1/2 effectors, and the signaling association with ERK1/2, calcium activation, and YAP mechanosensor, thus providing a mechanistic link between Plexin-B2-mediated cytoskeletal tension and stem cell physiology. Plexin-B2-deficient stem cells exhibit premature lineage commitment, and a balanced level of Plexin-B2 activity is critical for maintaining cytoarchitectural integrity of the developing neuroepithelium, as modeled in cerebral organoids. Our studies thus establish a significant function of Plexin-B2 in orchestrating cytoskeletal tension and cell-cell/cell-matrix adhesion, therefore solidifying the importance of collective cell mechanics in governing stem cell physiology and tissue morphogenesis.
Wigner solids of domain wall skyrmions
Authors: Yang Kaifeng , Nagase Katsumi , Hirayama Yoshiro , Mishima Tetsuya D. , Santos Michael B. , Liu Hongwu
Published: October 2021

Detection and characterization of a different type of topological excitations, namely the domain wall (DW) skyrmion, has received increasing attention because the DW is ubiquitous from condensed matter to particle physics and cosmology. Here we present experimental evidence for the DW skyrmion as the ground state stabilized by long-range Coulomb interactions in a quantum Hall ferromagnet. We develop an alternative approach using nonlocal resistance measurements together with a local NMR probe to measure the effect of low current-induced dynamic nuclear polarization and thus to characterize the DW under equilibrium conditions. The dependence of nuclear spin relaxation in the DW on temperature, filling factor, quasiparticle localization, and effective magnetic fields allows us to interpret this ground state and its possible phase transitions in terms of Wigner solids of the DW skyrmion. These results demonstrate the importance of studying the intrinsic properties of quantum states that has been largely overlooked.
Individualised and non-contact post-mortem interval determination of human bodies using visible and thermal 3D imaging
Authors: Wilk Leah S. , Edelman Gerda J. , Roos Martin , Clerkx Mara , Dijkman Inge , Melgar Jordi Vera , Oostra Roelof-Jan , Aalders Maurice C. G.
Published: October 2021

Determining the time since death, i.e., post-mortem interval (PMI), often plays a key role in forensic investigations. The current standard PMI-estimation method empirically correlates rectal temperatures and PMIs, frequently necessitating subjective correction factors. To overcome this, we previously developed a thermodynamic finite-difference (TFD) algorithm, providing a rigorous method to simulate post-mortem temperatures of bodies assuming a straight posture. However, in forensic practice, bodies are often found in non-straight postures, potentially limiting applicability of this algorithm in these cases. Here, we develop an individualised approach, enabling PMI reconstruction for bodies in arbitrary postures, by combining photogrammetry and TFD modelling. Utilising thermal photogrammetry, this approach also represents the first non-contact method for PMI reconstruction. The performed lab and crime scene validations reveal PMI reconstruction accuracies of 0.26 h ± 1.38 h for true PMIs between 2 h and 35 h and total procedural durations of ~15 min. Together, these findings broaden the potential applicability of TFD-based PMI reconstruction.
Molybdenum isotopes unmask slab dehydration and melting beneath the Mariana arc
Authors: Li Hong-Yan , Zhao Rui-Peng , Li Jie , Tamura Yoshihiko , Spencer Christopher , Stern Robert J. , Ryan Jeffrey G. , Xu Yi-Gang
Published: October 2021

How serpentinites in the forearc mantle and subducted lithosphere become involved in enriching the subarc mantle source of arc magmas is controversial. Here we report molybdenum isotopes for primitive submarine lavas and serpentinites from active volcanoes and serpentinite mud volcanoes in the Mariana arc. These data, in combination with radiogenic isotopes and elemental ratios, allow development of a model whereby shallow, partially serpentinized and subducted forearc mantle transfers fluid and melt from the subducted slab into the subarc mantle. These entrained forearc mantle fragments are further metasomatized by slab fluids/melts derived from the dehydration of serpentinites in the subducted lithospheric slab. Multistage breakdown of serpentinites in the subduction channel ultimately releases fluids/melts that trigger Mariana volcanic front volcanism. Serpentinites dragged down from the forearc mantle are likely exhausted at >200 km depth, after which slab-derived serpentinites are responsible for generating slab melts.
Iridium metallene oxide for acidic oxygen evolution catalysis
Authors: Dang Qian , Lin Haiping , Fan Zhenglong , Ma Lu , Shao Qi , Ji Yujin , Zheng Fangfang , Geng Shize , Yang Shi-Ze , Kong Ningning , Zhu Wenxiang , Li Youyong , Liao Fan , Huang Xiaoqing , Shao Mingwang
Published: October 2021

Exploring new materials is essential in the field of material science. Especially, searching for optimal materials with utmost atomic utilization, ideal activities and desirable stability for catalytic applications requires smart design of materials’ structures. Herein, we report iridium metallene oxide: 1 T phase-iridium dioxide (IrO2) by a synthetic strategy combining mechanochemistry and thermal treatment in a strong alkaline medium. This material demonstrates high activity for oxygen evolution reaction with a low overpotential of 197 millivolt in acidic electrolyte at 10 milliamperes per geometric square centimeter (mA cmgeo−2). Together, it achieves high turnover frequencies of 4.2 sUPD−1 (3.0 sBET−1) at 1.50 V vs. reversible hydrogen electrode. Furthermore, 1T-IrO2 also shows little degradation after 126 hours chronopotentiometry measurement under the high current density of 250 mA cmgeo−2 in proton exchange membrane device. Theoretical calculations reveal that the active site of Ir in 1T-IrO2 provides an optimal free energy uphill in *OH formation, leading to the enhanced performance. The discovery of this 1T-metallene oxide material will provide new opportunities for catalysis and other applications.
Pain sensing neurons promote tissue regeneration in adult mice
Authors: Rabiller Lise , Labit Elodie , Guissard Christophe , Gilardi Silveric , Guiard Bruno P. , Moulédous Lionel , Silva Marine , Mithieux Gilles , Pénicaud Luc , Lorsignol Anne , Casteilla Louis , Dromard Cécile
Published: October 2021

Tissue repair after injury in adult mammals, usually results in scarring and loss of function in contrast to lower vertebrates such as the newt and zebrafish that regenerate. Understanding the regulatory processes that guide the outcome of tissue repair is therefore a concerning challenge for regenerative medicine. In multiple regenerative animal species, the nerve dependence of regeneration is well established, but the nature of the innervation required for tissue regeneration remains largely undefined. Using our model of induced adipose tissue regeneration in adult mice, we demonstrate here that nociceptive nerves promote regeneration and their removal impairs tissue regeneration. We also show that blocking the receptor for the nociceptive neuropeptide calcitonin gene-related peptide (CGRP) inhibits regeneration, whereas CGRP administration induces regeneration. These findings reveal that peptidergic nociceptive neurons are required for adult mice tissue regeneration.
High-confidence structural annotation of metabolites absent from spectral libraries
Authors: Hoffmann Martin A. , Nothias Louis-Félix , Ludwig Marcus , Fleischauer Markus , Gentry Emily C. , Witting Michael , Dorrestein Pieter C. , Dührkop Kai , Böcker Sebastian
Published: October 2021

Untargeted metabolomics experiments rely on spectral libraries for structure annotation, but, typically, only a small fraction of spectra can be matched. Previous in silico methods search in structure databases but cannot distinguish between correct and incorrect annotations. Here we introduce the COSMIC workflow that combines in silico structure database generation and annotation with a confidence score consisting of kernel densityPvalue estimation and a support vector machine with enforced directionality of features. On diverse datasets, COSMIC annotates a substantial number of hits at low false discovery rates and outperforms spectral library search. To demonstrate that COSMIC can annotate structures never reported before, we annotated 12 natural bile acids. The annotation of nine structures was confirmed by manual evaluation and two structures using synthetic standards. In human samples, we annotated and manually validated 315 molecular structures currently absent from the Human Metabolome Database. Application of COSMIC to data from 17,400 metabolomics experiments led to 1,715 high-confidence structural annotations that were absent from spectral libraries.
Examining learning coherence in group decision-making: triads vs. tetrads
Authors: Harada Tsutomu
Published: October 2021

This study examined whether three heads are better than four in terms of performance and learning properties in group decision-making. It was predicted that learning incoherence took place in tetrads because the majority rule could not be applied when two subgroups emerged. As a result, tetrads underperformed triads. To examine this hypothesis, we adopted a reinforcement learning framework using simple Q-learning and estimated learning parameters. Overall, the results were consistent with the hypothesis. Further, this study is one of a few attempts to apply a computational approach to learning behavior in small groups. This approach enables the identification of underlying learning parameters in group decision-making.
A spatial analysis of lime resources and their potential for improving soil magnesium concentrations and pH in grassland areas of England and Wales
Authors: Bide T. , Ander E. L. , Broadley M. R.
Published: October 2021

Magnesium (Mg) is essential for animal health. Low Mg status (hypomagnesaemia) can be potentially fatal in ruminants, like cattle and sheep, and is widespread in Europe with economic impacts on farming. The application of Mg-rich agricultural lime products can help to ensure pasture forage consumed by animals contains sufficient Mg and, in areas of low pH, has the dual benefit of reducing soil acidity to levels best suited for grass production. This aim of this study was to determine if Mg-rich lime products could be used in a more effective manner in agricultural production systems. Potential resources of carbonate rocks (limestone, dolostone and chalk) in the UK, and their Mg:Ca status were identified, using datasets from the British Geological Survey (BGS). These data were combined with the locations of agricultural lime quarries, and areas where soils are likely to be deficient in Mg and/or require liming. Areas of potential demand for Mg-rich agricultural lime include areas in south east Wales, the Midlands and North East England. Although, areas where this may be an effective solution to low soil Mg values are restricted by the availability of suitable products. Conversely, areas of low soil pH in England and Wales are often found close to quarries with the ability to supply high Ca limes, suggesting that the low rates of lime use and liming is not due to supply factors. This study provides information that can help to guide on-farm decision making for use of Mg-rich and other lime resources. This could be used in conjunction with other options to reduce risks of Mg deficiency in livestock, and improve soil pH.
Phase angle by electrical bioimpedance is a predictive factor of hospitalisation, falls and mortality in patients with cirrhosis
Authors: Román Eva , Poca Maria , Amorós-Figueras Gerard , Rosell-Ferrer Javier , Gely Cristina , Nieto Juan C. , Vidal Silvia , Urgell Eulàlia , Ferrero-Gregori Andreu , Alvarado-Tapias Edilmar , Cuyàs Berta , Hernández Elvira , Santesmases Rosalia , Guarner Carlos , Escorsell Àngels , Soriano German
Published: October 2021

The phase angle is a versatile measurement to assess body composition, frailty and prognosis in patients with chronic diseases. In cirrhosis, patients often present alterations in body composition that are related to adverse outcomes. The phase angle could be useful to evaluate prognosis in these patients, but data are scarce. The aim was to analyse the prognostic value of the phase angle to predict clinically relevant events such as hospitalisation, falls, and mortality in patients with cirrhosis. Outpatients with cirrhosis were consecutively included and the phase angle was determined by electrical bioimpedance. Patients were prospectively followed to determine the incidence of hospitalisations, falls, and mortality. One hundred patients were included. Patients with phase angle ≤ 4.6° (n = 31) showed a higher probability of hospitalisation (35% vs 11%, p = 0.003), falls (41% vs 11%, p = 0.001) and mortality (26% vs 3%, p = 0.001) at 2-year follow-up than patients with PA > 4.6° (n = 69). In the multivariable analysis, the phase angle and MELD-Na were independent predictive factors of hospitalisation and mortality. Phase angle was the only predictive factor for falls. In conclusion, the phase angle showed to be a predictive marker for hospitalisation, falls, and mortality in outpatients with cirrhosis.
Association between serum uric acid and depressive symptoms stratified by low-grade inflammation status
Authors: Rhee Sang Jin , Lee Hyunju , Ahn Yong Min
Published: October 2021

Despite increasing evidence for an association between circulating uric acid (UA) and depression, the directionality of this association remains unclear and is potentially moderated by low-grade inflammation. Thus, the present study aimed to investigate the cross-sectional association between serum UA concentration and depressive symptoms in Korean individuals with and without low-grade inflammation, as measured using serum high-specific C-reactive protein (hs-CRP) levels. The final study sample comprised 4188 participants, aged 19–79 years, from the Korea National Health and Nutrition Examination Study 2016. Data on serum uric acid (UA) concentrations, serum hs-CRP levels, Patient Health Questionnaire-9 (PHQ-9) scores, and relative covariates were retrieved. Negative binomial regression with adjustment for the complex sample design was used to analyze the associations. After adjusting for covariates, log-transformed serum UA concentrations and total PHQ-9 scores were positively associated (incidence rate ratio [IRR] = 1.34 [95% confidence interval [CI] = 1.09–1.66]) for participants without low-grade inflammation and inversely associated (IRR = 0.64 [95% CI = 0.45–0.92]) for participants with low-grade inflammation. In conclusion, the direction of the association between serum UA and depressive symptoms was the opposite in participants with and without low-grade inflammation. The study has the limitation of potential uncontrolled confounders.
Influence of the 2015–2016 El Niño on the record-breaking mangrove dieback along northern Australia coast
Authors: Abhik S. , Hope Pandora , Hendon Harry H. , Hutley Lindsay B. , Johnson Stephanie , Drosdowsky Wasyl , Brown Josephine R. , Duke Norman C.
Published: October 2021

This study investigates the underlying climate processes behind the largest recorded mangrove dieback event along the Gulf of Carpentaria coast in northern Australia in late 2015. Using satellite-derived fractional canopy cover (FCC), variation of the mangrove canopies during recent decades are studied, including a severe dieback during 2015–2016. The relationship between mangrove FCC and climate conditions is examined with a focus on the possible role of the 2015–2016 El Niño in altering favorable conditions sustaining the mangroves. The mangrove FCC is shown to be coherent with the low-frequency component of sea level height (SLH) variation related to the El Niño Southern Oscillation (ENSO) cycle in the equatorial Pacific. The SLH drop associated with the 2015–2016 El Niño is identified to be the crucial factor leading to the dieback event. A stronger SLH drop occurred during austral autumn and winter, when the SLH anomalies were about 12% stronger than the previous very strong El Niño events. The persistent SLH drop occurred in the dry season of the year when SLH was seasonally at its lowest, so potentially exposed the mangroves to unprecedented hostile conditions. The influence of other key climate factors is also discussed, and a multiple linear regression model is developed to understand the combined role of the important climate variables on the mangrove FCC variation.
Biological activity of chitosan inducing resistance efficiency of rice (Oryza sativa L.) after treatment with fungal based chitosan
Authors: Stanley-Raja Vethamonickam , Senthil-Nathan Sengottayan , Chanthini Kanagaraj Muthu-Pandian , Sivanesh Haridoss , Ramasubramanian Ramakrishnan , Karthi Sengodan , Shyam-Sundar Narayanan , Vasantha-Srinivasan Prabhakaran , Kalaivani Kandaswamy
Published: October 2021

Reduced pathogen resistance and management of the left-over rice stubble are among the most important challenges faced in rice cultivation. A novel and eco-friendly strategy to synthesise ‘Fungal Chitosan’ (FC) from Aspergillus niger using rice straw could serve as a sustainable treatment approach to improve both disease resistance and yields, while also effectively managing the rice stubble waste. The FC treatment promoted germination as well as growth parameters in rice varieties, TN1 (high yielding-susceptible) and PTB33 (low yielding-resistant) better than a commercial chitosan (PC). Treatments of exogenously applied FC to plants produced direct toxicity to Xoo, and reduced the BLB disease index by 39.9% in TN1. The capability of FC to trigger a cascade of defense pathways was evident from the measurable changes in the kinetics of defense enzymes, peroxidase (POD) and polyphenol oxidase (PPO). FC treatment increased levels of POD in TN1 by 59.4%, which was 35.3% greater than that of untreated PTB33. Therefore, the study demonstrated the effectiveness of FC treatments for use in agriculture as a potential biostimulant as well as protective agent against bacterial leaf blight, BLB, of rice (Oryza sativa) that could be produced from stubble waste and improve rice stubble management strategies.
The structure of the cereal leaf beetle (Oulema melanopus) microbiome depends on the insect’s developmental stage, host plant, and origin
Authors: Wielkopolan Beata , Krawczyk Krzysztof , Szabelska-Beręsewicz Alicja , Obrępalska-Stęplowska Aleksandra
Published: October 2021

Cereal leaf beetle (CLB, Oulema melanopus, Coleoptera, Chrysomelidae) is a serious agricultural pest that causes considerable damages to agricultural production. The aim of this study was to characterize the bacterial communities associated with larvae and imagoes of CLB collected from various cereal host species and locations. The bacterial profile was characterized by 16S rRNA gene sequencing at the V3-V4 hypervariable region. Using taxonomy-based analysis, the bacterial community of CLB containing 16 phyla, 26 classes, 49 orders, 78 families, 94 genera, and 63 species of bacteria was identified. The abundance of Wolbachia, Rickettsia, and Lactococcus genus was significantly higher in CLB imagoes than in larvae. Statistical analysis confirmed that the bacterial community of the larvae is more diverse in comparison to imagoes and that insects collected from spring barley and wheat are characterized by a much higher biodiversity level of bacterial genera and species than insects collected from other cereals. Obtained results indicated that the developmental stage, the host plant, and the insect’s sampling location affected the CLB’s microbiome. Additionally, the CLB core microbiome was determined. It consists of 2 genera (Wolbachia and Rickettsia) shared by at least 90% tested CLB insects, regardless of the variables analysed.
New﻿ extreme morphologies as exemplified by 100 million-year-old lacewing larvae
Authors: Haug Joachim T. , Baranov Viktor , Müller Patrick , Haug Carolin
Published: October 2021

Larvae of the group Holometabola (beetles, wasps, flies, moths and others) differ significantly in their morphology from their corresponding adults. In most larvae, appendages and other structures protruding from the body (antennae, palps, legs, trunk processes) appear less elongate than in their corresponding adults, providing the impression that these larvae are restricted to a certain degree in developing more elongate structures. We provide here numerous counterexamples of larvae of lacewings (Neuroptera). These include different forms of elongated antennae, mandibles, maxillae, labial palps, legs, trunk processes and neck regions. Most of these examples are larvae preserved in different types of 100 million-year-old amber. The longest neck region was found in an extant specimen. All these examples demonstrate that certain branches of Neuroptera indeed had larval forms that possessed strongly elongated structures. Hence there is no principal constraint that hinders holometabolan larvae to develop such structures.
Mitigating COVID-19 on a small-world network
Authors: Du Marvin
Published: October 2021

Continuous deterministic models have been widely used to guide non-pharmaceutical interventions (NPIs) to combat the spread of the coronavirus disease 2019 (COVID-19). The validity of continuous deterministic models is questionable because they fail to incorporate two important characteristics of human society: high clustering and low degree of separation. A small-world network model is used to study the spread of COVID-19, thus providing more reliable information to provide guidance to mitigate it. Optimal timing of lockdown and reopening society is investigated so that intervention measures to combat COVID-19 can work more efficiently. Several important findings are listed as follows: travel restrictions should be implemented as soon as possible; if ‘flattening the curve’ is the purpose of the interventions, measures to reduce community transmission need not be very strict so that the lockdown can be sustainable; the fraction of the population that is susceptible, rather than the levels of daily new cases and deaths, is a better criterion to decide when to reopen society; and society can be safely reopened when the susceptible population is still as high as 70%, given that the basic reproduction number is 2.5. Results from small-world network models can be significantly different than those from continuous deterministic models, and the differences are mainly due to a major shortfall intrinsically embedded in the continuous deterministic models. As such, small-world network models provide meaningful improvements over continuous deterministic models and therefore should be used in the mathematical modeling of infection spread to guide the present COVID-19 interventions. For future epidemics, the present framework of mathematical modeling can be a better alternative to continuous deterministic models.
Surveillance of SARS-CoV-2 lineage B.1.1.7 in Slovakia using a novel, multiplexed RT-qPCR assay
Authors: Boršová Kristína , Paul Evan D. , Kováčová Viera , Radvánszka Monika , Hajdu Roman , Čabanová Viktória , Sláviková Monika , Ličková Martina , Lukáčiková Ľubomíra , Belák Andrej , Roussier Lucia , Kostičová Michaela , Líšková Anna , Maďarová Lucia , Štefkovičová Mária , Reizigová Lenka , Nováková Elena , Sabaka Peter , Koščálová Alena , Brejová Broňa , Staroňová Edita , Mišík Matej , Vinař Tomáš , Nosek Jozef , Čekan Pavol , Klempa Boris
Published: October 2021

The emergence of a novel SARS-CoV-2 B.1.1.7 variant sparked global alarm due to increased transmissibility, mortality, and uncertainty about vaccine efficacy, thus accelerating efforts to detect and track the variant. Current approaches to detect B.1.1.7 include sequencing and RT-qPCR tests containing a target assay that fails or results in reduced sensitivity towards the B.1.1.7 variant. Since many countries lack genomic surveillance programs and failed assays detect unrelated variants containing similar mutations as B.1.1.7, we used allele-specific PCR, and judicious placement of LNA-modified nucleotides to develop an RT-qPCR test that accurately and rapidly differentiates B.1.1.7 from other SARS-CoV-2 variants. We validated the test on 106 clinical samples with lineage status confirmed by sequencing and conducted a country-wide surveillance study of B.1.1.7 prevalence in Slovakia. Our multiplexed RT-qPCR test showed 97% clinical sensitivity and retesting 6,886 SARS-CoV-2 positive samples obtained during three campaigns performed within one month, revealed pervasive spread of B.1.1.7 with an average prevalence of 82%. Labs can easily implement this test to rapidly scale B.1.1.7 surveillance efforts and it is particularly useful in countries with high prevalence of variants possessing only the ΔH69/ΔV70 deletion because current strategies using target failure assays incorrectly identify these as putative B.1.1.7 variants.
E. coli aggregation and impaired cell division after terahertz irradiation
Authors: Peltek Sergey , Meshcheryakova Irina , Kiseleva Elena , Oshchepkov Dmitry , Rozanov Alexei , Serdyukov Danil , Demidov Evgeniy , Vasiliev Gennady , Vinokurov Nikolay , Bryanskaya Alla , Bannikova Svetlana , Popik Vasiliy , Goryachkovskaya Tatyana
Published: October 2021

In this study we demonstrated that exposure of Escherichia coli (E. coli) to terahertz (THz) radiation resulted in a change in the activities of the tdcABCDEFGR and matA–F genes (signs of cell aggregation), gene yjjQ (signs of suppression of cell motility), dicABCF, FtsZ, and minCDE genes (signs of suppression of cell division), sfmACDHF genes (signs of adhesin synthesis), yjbEFGH and gfcA genes (signs of cell envelope stabilization). Moreover, THz radiation induced E. coli csg operon genes of amyloid biosynthesis. Electron microscopy revealed that the irradiated bacteria underwent increased aggregation; 20% of them formed bundle-like structures consisting of two to four pili clumped together. This could be the result of changes in the adhesive properties of the pili. We also found aberrations in cell wall structure in the middle part of the bacterial cell; these aberrations impaired the cell at the initial stages of division and resulted in accumulation of long rod-like cells. Overall, THz radiation was shown to have adverse effects on bacterial populations resulting in cells with abnormal morphology.
Snapshot multicolor fluorescence imaging using double multiplexing of excitation and emission on a single detector
Authors: Dorozynska Karolina , Ek Simon , Kornienko Vassily , Andersson David , Andersson Alexandra , Ehn Andreas , Kristensson Elias
Published: October 2021

Fluorescence-based multispectral imaging of rapidly moving or dynamic samples requires both fast two-dimensional data acquisition as well as sufficient spectral sensitivity for species separation. As the number of fluorophores in the experiment increases, meeting both these requirements becomes technically challenging. Although several solutions for fast imaging of multiple fluorophores exist, they all have one main restriction; they rely solely on spectrally resolving either the excitation- or the emission characteristics of the fluorophores. This inability directly limits how many fluorophores existing methods can simultaneously distinguish. Here we present a snapshot multispectral imaging approach that not only senses the excitation and emission characteristics of the probed fluorophores but also all cross term combinations of excitation and emission. To the best of the authors’ knowledge, this is the only snapshot multispectral imaging method that has this ability, allowing us to even sense and differentiate between light of equal wavelengths emitted from the same fluorescing species but where the signal components stem from different excitation sources. The current implementation of the technique allows us to simultaneously gather 24 different spectral images on a single detector, from which we demonstrate the ability to visualize and distinguish up to nine fluorophores within the visible wavelength range.
Evidence that two instead of one defective interfering RNA in influenza A virus-derived defective interfering particles (DIPs) does not enhance antiviral activity
Authors: Bdeir Najat , Arora Prerna , Gärtner Sabine , Pöhlmann Stefan , Winkler Michael
Published: October 2021

Influenza A virus (IAV) infection constitutes a significant health threat. Defective interfering particles (DIPs) can arise during IAV infection and inhibit spread of wild type (WT) IAV. DIPs harbor defective RNA segments, termed DI RNAs, that usually contain internal deletions and interfere with replication of WT viral RNA segments. Here, we asked whether DIPs harboring two instead of one DI RNA exert increased antiviral activity. For this, we focused on DI RNAs derived from segments 1 and 3, which encode the polymerase subunits PB2 and PA, respectively. We demonstrate the successful production of DIPs harboring deletions in segments 1 and/or 3, using cell lines that co-express PB2 and PA. Further, we demonstrate that DIPs harboring two instead of one DI RNA do not exhibit increased ability to inhibit replication of a WT RNA segment. Similarly, the presence of two DI RNAs did not augment the induction of the interferon-stimulated gene MxA and the inhibition of IAV infection. Collectively, our findings suggest that the presence of multiple DI RNAs derived from genomic segments encoding polymerase subunits might not result in increased antiviral activity.
Epidemiological and economic impact of COVID-19 in the US
Authors: Chen Jiangzhuo , Vullikanti Anil , Santos Joost , Venkatramanan Srinivasan , Hoops Stefan , Mortveit Henning , Lewis Bryan , You Wen , Eubank Stephen , Marathe Madhav , Barrett Chris , Marathe Achla
Published: October 2021

This research measures the epidemiological and economic impact of COVID-19 spread in the US under different mitigation scenarios, comprising of non-pharmaceutical interventions. A detailed disease model of COVID-19 is combined with a model of the US economy to estimate the direct impact of labor supply shock to each sector arising from morbidity, mortality, and lockdown, as well as the indirect impact caused by the interdependencies between sectors. During a lockdown, estimates of jobs that are workable from home in each sector are used to modify the shock to labor supply. Results show trade-offs between economic losses, and lives saved and infections averted are non-linear in compliance to social distancing and the duration of the lockdown. Sectors that are worst hit are not the labor-intensive sectors such as the Agriculture sector and the Construction sector, but the ones with high valued jobs such as the Professional Services, even after the teleworkability of jobs is accounted for. Additionally, the findings show that a low compliance to interventions can be overcome by a longer shutdown period and vice versa to arrive at similar epidemiological impact but their net effect on economic loss depends on the interplay between the marginal gains from averting infections and deaths, versus the marginal loss from having healthy workers stay at home during the shutdown.
Factors associated with the decline of malaria in Myanmar’s Ayeyarwady Region between 2013 and 2017
Authors: Gallalee Sarah , Ward Abigail V. , Aye Moe Moe , Aung Nang Khaing Zar , Dunn Julia C. , Lavenberg Stephen , Lourenço Christopher , Dunning Jillian , Thi Aung , Le Menach Arnaud , Tun Myat Min
Published: October 2021

The burden of malaria in Myanmar has declined rapidly in recent years; cases decreased from 333,871 in 2013 to 85,019 in 2017 (75% decrease). Decline of malaria in the Ayeyarwady Region of Myanmar reflects this trend with an 86% decrease in cases over this period. In this exploratory analysis, quantitative and qualitative information were assessed to explore potential factors responsible for the decline of malaria in Ayeyarwady. Data on malaria incidence, programmatic financing, surveillance, case management, vector control interventions, climate and ecological factors, and policies and guidelines spanning 2013 to 2017 were compiled. Poisson regression models that adjust for correlation were used to analyze the association between annual malaria case numbers with malaria intervention factors at the township level. Between 2013 and 2017, there was a decrease in mean township-level malaria incidence per 1000 from 3.03 (SD 4.59) to 0.34 (SD 0.79); this decline coincided with the implementation of the government’s multi-pronged malaria elimination strategy, an increase of approximately 50.8 million USD in malaria funding nationally, and a period of deforestation in the region. Increased funding in Ayeyarwady was invested in interventions associated with the decline in caseload, and the important roles of surveillance and case management should be maintained while Myanmar works towards malaria elimination.
Resistance, resilience, and recovery of salt marshes in the Florida Panhandle following Hurricane Michael
Authors: Castagno Katherine A. , Tomiczek Tori , Shepard Christine C. , Beck Michael W. , Bowden Alison A. , O’Donnell Kiera , Scyphers Steven B.
Published: October 2021

Characterizing the fragility, resistance, and resilience of marshes is critical for understanding their role in reducing storm damages and for helping to manage the recovery of these natural defenses. This study uses high-resolution aerial imagery to quantify the impacts of Hurricane Michael, a category 5 hurricane, on coastal salt marshes in the Florida Panhandle, USA. Marsh damage was classified into several categories, including deposition of sediment or wrack, fallen trees, vegetation loss, and conversion to open water. The marshes were highly resistant to storm damages even under extreme conditions; only 2% of the 173,259 km2 of marshes in the study area were damaged—a failure rate much lower than that of artificial defenses. Marshes may be more resistant than resilient to storm impacts; damaged marshes were slow to recover, and only 16% of damaged marshes had recovered 6 months after landfall. Marsh management mattered for resistance and resilience; marshes on publicly-managed lands were less likely to be damaged and more likely to recover quickly from storm impacts than marshes on private land, emphasizing the need to incentivize marsh management on private lands. These results directly inform policy and practice for hazard mitigation, disaster recovery, adaptation, and conservation, particularly given the potential for more intense hurricane landfalls as the climate changes.
The beta component of gamma-band auditory steady-state responses in patients with schizophrenia
Authors: Metzner Christoph , Steuber Volker
Published: October 2021

The mechanisms underlying circuit dysfunctions in schizophrenia (SCZ) remain poorly understood. Auditory steady-state responses (ASSRs), especially in the gamma and beta band, have been suggested as a potential biomarker for SCZ. While the reduction of 40 Hz power for 40 Hz drive has been well established and replicated in SCZ patients, studies are inconclusive when it comes to an increase in 20 Hz power during 40 Hz drive. There might be several factors explaining the inconsistencies, including differences in the sensitivity of the recording modality (EEG vs MEG), differences in stimuli (click-trains vs amplitude-modulated tones) and large differences in the amplitude of the stimuli. Here, we used a computational model of ASSR deficits in SCZ and explored the effect of three SCZ-associated microcircuit alterations: reduced GABA activity, increased GABA decay times and NMDA receptor hypofunction. We investigated the effect of input strength on gamma (40 Hz) and beta (20 Hz) band power during gamma ASSR stimulation and saw that the pronounced increase in beta power during gamma stimulation seen experimentally could only be reproduced in the model when GABA decay times were increased and only for a specific range of input strengths. More specifically, when the input was in this specific range, the rhythmic drive at 40 Hz produced a strong 40 Hz rhythm in the control network; however, in the ‘SCZ-like’ network, the prolonged inhibition led to a so-called ‘beat-skipping’, where the network would only strongly respond to every other input. This mechanism was responsible for the emergence of the pronounced 20 Hz beta peak in the power spectrum. The other two microcircuit alterations were not able to produce a substantial 20 Hz component but they further narrowed the input strength range for which the network produced a beta component when combined with increased GABAergic decay times. Our finding that the beta component only existed for a specific range of input strengths might explain the seemingly inconsistent reporting in experimental studies and suggests that future ASSR studies should systematically explore different amplitudes of their stimuli. Furthermore, we provide a mechanistic link between a microcircuit alteration and an electrophysiological marker in schizophrenia and argue that more complex ASSR stimuli are needed to disentangle the nonlinear interactions of microcircuit alterations. The computational modelling approach put forward here is ideally suited to facilitate the development of such stimuli in a theory-based fashion.
Study on the relationship between DNA methylation of target CpG sites in peripheral blood and gestational diabetes during early pregnancy
Authors: Wang Xiaolei , Huang Jin , Zheng Yixiang , Long Sisi , Lin Huijun , Zhang Na , Tian Mengyuan , Wu Xinrui , An Rongjing , Ma Shujuan , Tan Hongzhuan
Published: October 2021

Genome-wide DNA methylation profiling have been used to find maternal CpG sites related to the occurrence of gestational diabetes mellitus (GDM). However, none of these differential sites found has been verified in a larger sample. Here, our aim was to evaluate whether first trimester changes in target CpG sites in the peripheral blood of pregnancy women predict subsequent development of GDM. This nested case–control study was based upon an early pregnancy follow-up cohort (ChiCTR1900020652). Target CpG sites were extracted from related published literature and bioinformatics analysis. The DNA methylation levels at 337 CpG sites of 80 GDM cases and 80 matched healthy controls during the early pregnancy (10–15 weeks) were assessed using MethylTarget sequencing. The best cut-off level for methylation of CpG site was determined using the generated ROC curve. The independent effect of CpG site methylation status on GDM was analyzed using conditional logistic regression. Methylation levels at 6 CpG sites were significantly higher in the GDM group than in controls, whereas those at another 6 CpG sites were significantly lower (FDR < 0.05). The area under the ROC curve at each methylation level of the significant CpG sites ranged between 0.593 and 0.650 for the occurrence of GDM. After adjusting for possible confounders, the hypermethylation status of CpG site 68167324 (OR = 3.168, 1.038–9.666) and 24837915 (OR = 5.232, 1.659–16.506) was identified as more strongly associated with GDM; meanwhile, the hypermethylation of CpG site 157130156 (OR = 0.361, 0.135–0.966) and 89438648 (OR = 0.206, 0.065–0.655) might indicate lower risk of GDM. The methylation status of target CpG sites in the peripheral blood of pregnant women during the first trimester may be associated with GDM pathogenesis, and has potential as a predictor of GDM.
Self-assembly of a strapped linear porphyrin oligomer on HOPG
Authors: Bellamy-Carter Abigail , Roche Cécile , Anderson Harry L. , Saywell Alex
Published: October 2021

Polymeric structures based on porphyrin units exhibit a range of complex properties, such as nanoscale charge transport and quantum interference effects, and have the potential to act as biomimetic materials for light-harvesting and catalysis. These functionalities are based upon the characteristics of the porphyrin monomers, but are also emergent properties of the extended polymer system. Incorporation of these properties within solid-state devices requires transfer of the polymers to a supporting substrate, and may require a high-degree of lateral order. Here we show that highly ordered self-assembled structures can be formed via a simple solution deposition protocol; for a strapped linear porphyrin oligomer adsorbed on a highly oriented pyrolytic graphite (HOPG) substrate. Two distinct molecule–molecule interactions are observed to drive the formation of two molecular phases (‘Interdigitated’ and ‘Bridge-stabilised’) characterised by scanning tunnelling microscopy, providing information on the unit cell dimensions and self-assembled structure. The concentration dependence of these phases is investigated, and we conclude that the bridge-stabilised phase is a thermodynamically stable structure at room temperature.
Impact of ionic liquids on absorption behaviour of natural fibers/biopolyethylene biocomposites
Authors: Rakowska Joanna , Węgrzyn Magdalena , Rudnik Ewa
Published: October 2021

For many years, there has been a growing interest in technologies enabling the replacement of conventional polymer composites with new materials made from renewable raw materials. It is important to assess the behaviour of biocomposites in various environments, including humid conditions. Recently, ionic liquids have been studied as potential modificators of polymers properties, especially flame retardants. In previous study the impact of ionic liquids on thermal and mechanical properties of biocomposites was assessed. In this study the influence of ionic liquids on moisture absorption properties of biocomposites at different relative humidities (RH) was assessed. The biocomposites were built from polyethylene from renewable resources reinforced with flax or hemp fibers. The effect of the addition of 0.5, 1.0, 2.5 and 5 wt.% phosphonium ionic liquids on the moisture absorption properties of biopolyethylene biocomposite reinforced with natural fibers were tested. Mixtures of biopolyethylene, natural fibers and ionic liquid were calendered at 180 °C and then were compounded by injection moulding. The prepared samples were then characterized for their moisture uptake at 30%, 50% and 100% RH. Moisture absorption by biocomposites depended on the structure of the ionic liquid and the type of fiber. The saturation of moisture of about 0.054% was found for samples modified with tributylethylphosphonium diethyl phosphate and reinforced with flax and hemp fibers at RH 100%. The environmental resistance of the materials was found to be improved after the addition of trihexyltetradecylphosphonium bis (2,4,4-trimethylpentyl) phosphinate. Biocomposites with hemp fibers showed slightly less absorption than with flax fibers. It was also observed that ionic liquids: (bis (2,4,4-trimethylpentyl) phosphinate trihexyltetradecylphosphonate) and (bis (2-ethylhexyl) trihexyltetradecylphosphonium phosphate) protect PE biocomposites with plant fibers against mold in high humidity conditions (RH 100%).
FH ALERT: efficacy of a novel approach to identify patients with familial hypercholesterolemia
Authors: Fath Felix , Bengeser Andreas , Barresi Mathias , Binner Priska , Schwab Stefanie , Ray Kausik K. , Krämer Bernhard K. , Fraass Uwe , März Winfried
Published: October 2021

Diagnosis rates of familial hypercholesterolemia (FH) remain low. We implemented FH ALERT to assess whether alerting physicians for the possibility of FH impacted additional diagnostic activity. The study was conducted from SYNLAB laboratory Weiden (Bavaria). Beyond common reporting of LDL-C or TC, 1411 physicians covering approximately a population of 1.5 million people were eligible to receive an alert letter (AL) including information on FH, if laboratory results exceeded thresholds as follows: adults LDL-C ≥ 190–250 mg/dl (to convert into mmol/l multiply with 0.0259), TC ≥ 250 to ≤ 310 mg/dl (probable suspicion); LDL-C > 250 mg/dl and TC > 310 mg/dl (strong suspicion). Persons below 18 years were alerted for LDL-C  140 mg/dl and TC ≥ 200 mg/dl (strong suspicion). Patients above 60 years were excluded. Our readouts were characteristics of involved physicians, rate of ALs issued, acceptance, and subsequent diagnostic activity. Physicians were mainly general practitioners in ambulatory care. 75% of the ordered tests were for TC, 25% for LDL-C. We issued 3512 ALs (~ 5% of tests) triggered by 2846 patients. 86% of eligible physicians stayed with the initiative, 32.7% were alerted, and 70% were positive upon call-center survey. We registered 101 new visitors of www.fhscore.eu and sent out 93 kits for genetics. Thereof, 26 were returned and 5 patients were positive for FH. Physicians were in general open to our approach. Although genetic testing was taken up with caution, this 3-months pilot examination resulted in a greater rate of patients with FH diagnosed than previous screening projects. Further education on FH in primary care is required to improve FH detection in the community.
Care need and dry mouth as risk indicators for impaired taste and smell
Authors: Hummelsheim Mara-Zoe , Hamacher Stefanie , Hagemeier Anna , Noack Michael Johannes , Barbe Anna Greta
Published: October 2021

To identify whether reduced saliva secretion or xerostomia symptoms are risk indicators for impaired taste and smell, depending on age and care needs. This cross-sectional study evaluated taste and smell in patients categorized into different age groups (<65> years) and different care need, with and without dry mouth. Of the 185 patients included, 119 were classified as “dry mouth” and 66 as “without dry mouth”. Overall, 103 (55.7%) were female and 37 (20%) needed care. There was no difference between “dry mouth” and “without dry mouth” regarding identification of odors or tastes, but a difference in the number of correctly identified odors and tastes in favor of “without care need” patients (p < 0.05). The ability to identify smells and tastes was negatively influenced by age, number of medications, and number of comorbidities, but subjective dry mouth had no impact. According to our results, subjective dry mouth is not a risk factor for an impaired ability to recognize smells and tastes. However, care need representing age, the number of medications taken, and the number of chronic comorbidities is a risk indicator.