bluuebunny/crossref_metadata_2025 huggingface dataset:
Metavinculin modulates force transduction in cell adhesion sites
Authors: Kanoldt Verena , Kluger Carleen , Barz Christiane , Schweizer Anna-Lena , Ramanujam Deepak , Windgasse Lukas , Engelhardt Stefan , Chrostek-Grashoff Anna , Grashoff Carsten
Published: December 2020

Vinculin is a ubiquitously expressed protein, crucial for the regulation of force transduction in cells. Muscle cells express a vinculin splice-isoform called metavinculin, which has been associated with cardiomyopathies. However, the molecular function of metavinculin has remained unclear and its role for heart muscle disorders undefined. Here, we have employed a set of piconewton-sensitive tension sensors to probe metavinculin mechanics in cells. Our experiments reveal that metavinculin bears higher molecular forces but is less frequently engaged as compared to vinculin, leading to altered force propagation in cell adhesions. In addition, we have generated knockout mice to investigate the consequences of metavinculin loss in vivo. Unexpectedly, these animals display an unaltered tissue response in a cardiac hypertrophy model. Together, the data reveal that the transduction of cell adhesion forces is modulated by expression of metavinculin, yet its role for heart muscle function seems more subtle than previously thought.
Spin–valley Hall phenomena driven by Van Hove singularities in blistered graphene
Authors: Farooq M. Umar , Hashmi Arqum , Ono Tomoya , Huang Li
Published: December 2020

Using first-principles calculations, we investigate the possibility of realizing valley Hall effects (VHE) in blistered graphene sheets. We show that the Van Hove singularities (VHS) induced by structural deformations can give rise to interesting spin–valley Hall phenomena. The broken degeneracy of spin degree of freedom results in spin-filtered VH states and the valley conductivity have a Hall plateau of ±e2/2h, while the blistered structures with time-reversal symmetry show the VHE with the opposite sign of $$\sigma _{xy}^{K/K^{\prime}}$$

σ

x
y

K
/

K

′

(e2/2h) in the two valleys. Remarkably, these results show that the distinguishable chiral valley pseudospin state can occur even in the presence of VHS induced spin splitting. The robust chiral spin–momentum textures in both massless and massive Dirac cones of the blistered systems indicate significant suppression of carrier back-scattering. Our study provides a different approach to realize spin-filtered and spin-valley contrasting Hall effects in graphene-based devices without any external field.
A combined microphysiological-computational omics approach in dietary protein evaluation
Authors: Jochems Paulus G. M. , Keusters Willem R. , America Antoine H. P. , Rietveld Pascale C. S. , Bastiaan-Net Shanna , Ariëns Renata M. C. , Tomassen Monic M. M. , Lewis Fraser , Li Yang , Westphal Koen G. C. , Garssen Johan , Wichers Harry J. , van Bergenhenegouwen Jeroen , Masereeuw Rosalinde
Published: December 2020

Food security is under increased pressure due to the ever-growing world population. To tackle this, alternative protein sources need to be evaluated for nutritional value, which requires information on digesta peptide composition in comparison to established protein sources and coupling to biological parameters. Here, a combined experimental and computational approach is presented, which compared seventeen protein sources with cow’s whey protein concentrate (WPC) as the benchmark. In vitro digestion of proteins was followed by proteomics analysis and statistical model-based clustering. Information on digesta peptide composition resulted in 3 cluster groups, primarily driven by the peptide overlap with the benchmark protein WPC. Functional protein data was then incorporated in the computational model after evaluating the effects of eighteen protein digests on intestinal barrier integrity, viability, brush border enzyme activity, and immune parameters using a bioengineered intestine as microphysiological gut system. This resulted in 6 cluster groups. Biological clustering was driven by viability, brush border enzyme activity, and significant differences in immune parameters. Finally, a combination of proteomic and biological efficacy data resulted in 5 clusters groups, driven by a combination of digesta peptide composition and biological effects. The key finding of our holistic approach is that protein source (animal, plant or alternative derived) is not a driving force behind the delivery of bioactive peptides and their biological efficacy.
An open-source, end-to-end workflow for multidimensional photoemission spectroscopy
Authors: Xian R. Patrick , Acremann Yves , Agustsson Steinn Y. , Dendzik Maciej , Bühlmann Kevin , Curcio Davide , Kutnyakhov Dmytro , Pressacco Federico , Heber Michael , Dong Shuo , Pincelli Tommaso , Demsar Jure , Wurth Wilfried , Hofmann Philip , Wolf Martin , Scheidgen Markus , Rettig Laurenz , Ernstorfer Ralph
Published: December 2020

Characterization of the electronic band structure of solid state materials is routinely performed using photoemission spectroscopy. Recent advancements in short-wavelength light sources and electron detectors give rise to multidimensional photoemission spectroscopy, allowing parallel measurements of the electron spectral function simultaneously in energy, two momentum components and additional physical parameters with single-event detection capability. Efficient processing of the photoelectron event streams at a rate of up to tens of megabytes per second will enable rapid band mapping for materials characterization. We describe an open-source workflow that allows user interaction with billion-count single-electron events in photoemission band mapping experiments, compatible with beamlines at 3rdand 4rdgeneration light sources and table-top laser-based setups. The workflow offers an end-to-end recipe from distributed operations on single-event data to structured formats for downstream scientific tasks and storage to materials science database integration. Both the workflow and processed data can be archived for reuse, providing the infrastructure for documenting the provenance and lineage of photoemission data for future high-throughput experiments.
Lubricant film formation in rough surface non-conformal conjunctions subjected to GPa pressures and high slide-to-roll ratios
Authors: Hansen Jonny , Björling Marcus , Larsson Roland
Published: December 2020

A ball-on-disc machine was employed in a highly idealised setting to study the interplay between oil film formation and surface irregularities in single-sided rough elasto-hydrodynamic lubricated (EHL) conjunctions. The tests were operated under GPa pressures and high slide-to-roll ratios in a situation where the separating gap was smaller than the combined surface roughness height. Under the initial state of solid contact interference and with the operating conditions held fixed, surfaces were found to gradually conform such that a fully separating oil film of nanometre thickness eventually developed—a thin film lubrication state known as micro-EHL. Additionally, with a previously developed approach for 3D surface re-location analysis, we were able to very precisely specify the pertained nature of surface transformations, even at the asperity scale, by comparing the post-test surfaces to those in the virgin state. The surface roughness Sq was reduced by up to 17% after running-in, while the speed required for full film EHL was reduced by a remarkable 90%. Hence, full film EHL is possible even in cases where the Λ-ratio falsely suggests boundary lubrication. This discrepancy was attributed to the way surfaces are deformed inside the contact, i.e., through the establishment of micro-EHL.
Three-party quantum private computation of cardinalities of set intersection and union based on GHZ states
Authors: Zhang Cai , Long Yinxiang , Sun Zhiwei , Li Qin , Huang Qiong
Published: December 2020

Private Set Intersection Cardinality (PSI-CA) and Private Set Union Cardinality (PSU-CA) are two cryptographic primitives whereby two or more parties are able to obtain the cardinalities of the intersection and the union of their respective private sets, and the privacy of their sets is preserved. In this paper, we propose a three-party protocol to finish these tasks by using quantum resources, where every two, as well as three, parties can obtain the cardinalities of the intersection and the union of their private sets with the help of a semi-honest third party (TP). In our protocol, GHZ states play a role in encoding private information that will be used by TP to compute the cardinalities. We show that the presented protocol is secure against well-known quantum attacks. In addition, we analyze the influence of six typical kinds of Markovian noise on our protocol.
A biomimetic engineered bone platform for advanced testing of prosthetic implants
Authors: Sladkova-Faure Martina , Pujari-Palmer Michael , Öhman-Mägi Caroline , López Alejandro , Wang Hanbin , Engqvist Håkan , de Peppo Giuseppe Maria
Published: December 2020

Existing methods for testing prosthetic implants suffer from critical limitations, creating an urgent need for new strategies that facilitate research and development of implants with enhanced osseointegration potential. Herein, we describe a novel, biomimetic, human bone platform for advanced testing of implants in vitro, and demonstrate the scientific validity and predictive value of this approach using an assortment of complementary evaluation methods. We anchored titanium (Ti) and stainless steel (SS) implants into biomimetic scaffolds, seeded with human induced mesenchymal stem cells, to recapitulate the osseointegration process in vitro. We show distinct patterns of gene expression, matrix deposition, and mineralization in response to the two materials, with Ti implants ultimately resulting in stronger integration strength, as seen in other preclinical and clinical studies. Interestingly, RNAseq analysis reveals that the TGF-beta and the FGF2 pathways are overexpressed in response to Ti implants, while the Wnt, BMP, and IGF pathways are overexpressed in response to SS implants. High-resolution imaging shows significantly increased tissue mineralization and calcium deposition at the tissue-implant interface in response to Ti implants, contributing to a twofold increase in pullout strength compared to SS implants. Our technology creates unprecedented research opportunities towards the design of implants and biomaterials that can be personalized, and exhibit enhanced osseointegration potential, with reduced need for animal testing.
A Rab escort protein regulates the MAPK pathway that controls filamentous growth in yeast
Authors: Jamalzadeh Sheida , Pujari Atindra N. , Cullen Paul J.
Published: December 2020

MAPK pathways regulate different responses yet can share common components. Although core regulators of MAPK pathways are well known, new pathway regulators continue to be identified. Overexpression screens can uncover new roles for genes in biological processes and are well suited to identify essential genes that cannot be evaluated by gene deletion analysis. In this study, a genome-wide screen was performed to identify genes that, when overexpressed, induce a reporter (FUS1-HIS3) that responds to ERK-type pathways (Mating and filamentous growth or fMAPK) but not p38-type pathways (HOG) in yeast. Approximately 4500 plasmids overexpressing individual yeast genes were introduced into strains containing the reporter by high-throughput transformation. Candidate genes were identified by measuring growth as a readout of reporter activity. Fourteen genes were identified and validated by re-testing: two were metabolic controls (HIS3, ATR1), five had established roles in regulating ERK-type pathways (STE4, STE7, BMH1, BMH2, MIG2) and seven represent potentially new regulators of MAPK signaling (RRN6, CIN5, MRS6, KAR2, TFA1, RSC3, RGT2). MRS6 encodes a Rab escort protein and effector of the TOR pathway that plays a role in nutrient signaling. MRS6 overexpression stimulated invasive growth and phosphorylation of the ERK-type fMAPK, Kss1. Overexpression of MRS6 reduced the osmotolerance of cells and phosphorylation of the p38/HOG MAPK, Hog1. Mrs6 interacted with the PAK kinase Ste20 and MAPKK Ste7 by two-hybrid analysis. Based on these results, Mrs6 may selectively propagate an ERK-dependent signal. Identifying new regulators of MAPK pathways may provide new insights into signal integration among core cellular processes and the execution of pathway-specific responses.
Risk stratification for early-onset fetal growth restriction in women with abnormal serum biomarkers: a retrospective cohort study
Authors: Ormesher L. , Warrander L. , Liu Y. , Thomas S. , Simcox L. , Smith G. C. S. , Myers J. E. , Johnstone E. D.
Published: December 2020

Abnormal maternal serum biomarkers (AMSB), identified through the aneuploidy screening programme, are frequent incidental findings in pregnancy. They are associated with fetal growth restriction (FGR), but previous studies have not examined whether this association is with early-onset (< 34 weeks) or late-onset (> 34 weeks) FGR; as a result there is no consensus on management. The aims of this study were to determine the prevalence and phenotype of FGR in women with AMSB and test the predictive value of placental sonographic screening to predict early-onset FGR. 1196 pregnant women with AMSB underwent a 21–24 week “placental screen” comprising fetal and placental size, and uterine artery Doppler. Multivariable regression was used to calculate a predictive model for early-onset FGR (birthweight centile < 3rd/< 10th with absent umbilical end-diastolic flow, < 34 weeks). FGR prevalence was high (10.3%), however early-onset FGR was uncommon (2.3%). Placental screening effectively identified early-onset (area under the curve (AUC) 0.93, 95% confidence interval (CI) 0.87–1.00), but not late-onset FGR (AUC 0.70, 95% CI 0.64–0.75). Internal validation demonstrated robust performance for detection/exclusion of early-onset FGR. In this cohort, utilisation of our proposed algorithm with targeted fetal growth and Doppler surveillance, compared with universal comprehensive surveillance would have avoided 1044 scans, potentiating significant cost-saving for maternity services.
Heat stress elicits remodeling in the anther lipidome of peanut
Authors: Zoong Lwe Zolian S. , Welti Ruth , Anco Daniel , Naveed Salman , Rustgi Sachin , Narayanan Sruthi
Published: December 2020

Understanding the changes in peanut (Arachis hypogaea L.) anther lipidome under heat stress (HT) will aid in understanding the mechanisms of heat tolerance. We profiled the anther lipidome of seven genotypes exposed to ambient temperature (AT) or HT during flowering. Under AT and HT, the lipidome was dominated by phosphatidylcholine (PC), phosphatidylethanolamine (PE), and triacylglycerol (TAG) species (> 50% of total lipids). Of 89 lipid analytes specified by total acyl carbons:total carbon–carbon double bonds, 36:6, 36:5, and 34:3 PC and 34:3 PE (all contain 18:3 fatty acid and decreased under HT) were the most important lipids that differentiated HT from AT. Heat stress caused decreases in unsaturation indices of membrane lipids, primarily due to decreases in highly-unsaturated lipid species that contained 18:3 fatty acids. In parallel, the expression of Fatty Acid Desaturase 3-2 (FAD3-2; converts 18:2 fatty acids to 18:3) decreased under HT for the heat-tolerant genotype SPT 06-07 but not for the susceptible genotype Bailey. Our results suggested that decreasing lipid unsaturation levels by lowering 18:3 fatty-acid amount through reducing FAD3 expression is likely an acclimation mechanism to heat stress in peanut. Thus, genotypes that are more efficient in doing so will be relatively more tolerant to HT.
Epigenetic differences at the HTR2A locus in progressive multiple sclerosis patients
Authors: Maltby Vicki E. , Lea Rodney A. , Burnard Sean , Xavier Alexandre , Van Cao Thao , White Nicole , Kennedy Daniel , Groen Kira , Sanders Katherine A. , Seeto Rebecca , Bray Samara , Gresle Melissa , Laverick Louise , Butzkueven Helmut , Scott Rodney J. , Lechner-Scott Jeannette
Published: December 2020

The pathology of progressive multiple sclerosis (MS) is poorly understood. We have previously assessed DNA methylation in the CD4+ T cells of relapsing–remitting (RR) MS patients compared to healthy controls and identified differentially methylated regions (DMRs) in HLA-DRB1 and RNF39. This study aimed to investigate the DNA methylation profiles of the CD4+ T cells of progressive MS patients. DNA methylation was measured in two separate case/control cohorts using the Illumina 450K/EPIC arrays and data was analysed with the Chip Analysis Methylation Pipeline (ChAMP). Single nucleotide polymorphisms (SNPs) were assessed using the Illumina Human OmniExpress24 arrays and analysed using PLINK. Expression was assessed using the Illumina HT12 array and analysed in R using a combination of Limma and Illuminaio. We identified three DMRs at HTR2A, SLC17A9 and HDAC4 that were consistent across both cohorts. The DMR at HTR2A is located within the bounds of a haplotype block; however, the DMR remained significant after accounting for SNPs in the region. No expression changes were detected in any DMRs. HTR2A is differentially methylated in progressive MS independent of genotype. This differential methylation is not evident in RRMS, making it a potential biomarker of progressive disease.
Multimodal fusion with deep neural networks for leveraging CT imaging and electronic health record: a case-study in pulmonary embolism detection
Authors: Huang Shih-Cheng , Pareek Anuj , Zamanian Roham , Banerjee Imon , Lungren Matthew P.
Published: December 2020

Recent advancements in deep learning have led to a resurgence of medical imaging and Electronic Medical Record (EMR) models for a variety of applications, including clinical decision support, automated workflow triage, clinical prediction and more. However, very few models have been developed to integrate both clinical and imaging data, despite that in routine practice clinicians rely on EMR to provide context in medical imaging interpretation. In this study, we developed and compared different multimodal fusion model architectures that are capable of utilizing both pixel data from volumetric Computed Tomography Pulmonary Angiography scans and clinical patient data from the EMR to automatically classify Pulmonary Embolism (PE) cases. The best performing multimodality model is a late fusion model that achieves an AUROC of 0.947 [95% CI: 0.946–0.948] on the entire held-out test set, outperforming imaging-only and EMR-only single modality models.
Endophytic fungi protect tomato and nightshade plants against Tuta absoluta (Lepidoptera: Gelechiidae) through a hidden friendship and cryptic battle
Authors: Agbessenou Ayaovi , Akutse Komivi S. , Yusuf Abdullahi A. , Ekesi Sunday , Subramanian Sevgan , Khamis Fathiya M.
Published: December 2020

Endophytic fungi live within plant tissues without causing any harm to the host, promote its growth, and induce systemic resistance against pests and diseases. To mitigate the challenging concealed feeding behavior of immature stages of Tuta absoluta in both tomato (Solanum lycopersicum) and nightshade (Solanum scabrum) host plants, 15 fungal isolates were assessed for their endophytic and insecticidal properties. Twelve isolates were endophytic to both host plants with varied colonization rates. Host plants endophytically-colonized by Trichoderma asperellum M2RT4, Beauveria bassiana ICIPE 706 and Hypocrea lixii F3ST1 outperformed all the other isolates in reducing significantly the number of eggs laid, mines developed, pupae formed and adults emerged. Furthermore, the survival of exposed adults and F1 progeny was significantly reduced by Trichoderma sp. F2L41 and B. bassiana isolates ICIPE 35(4) and ICIPE 35(15) compared to other isolates. The results indicate that T. asperellum M2RT4, B. bassiana ICIPE 706 and H. lixii F3ST1 have high potential to be developed as endophytic-fungal-based biopesticide for the management of T. absoluta.
Development of a pVEC peptide-based ribonucleoprotein (RNP) delivery system for genome editing using CRISPR/Cas9 in Chlamydomonas reinhardtii
Authors: Kang Seongsu , Jeon Seungjib , Kim Seungcheol , Chang Yong Keun , Kim Yeu-Chun
Published: December 2020

Recent technical advances related to the CRISPR/Cas9-based genome editing system have enabled sophisticated genome editing in microalgae. Although the demand for research on genome editing in microalgae has increased over time, methodological research has not been established to date for the delivery of a ribonucleoprotein (Cas9/sgRNA complex) using a cell penetrating peptide into microalgal cell lines. Here, we present a ribonucleoprotein delivery system for Chlamydomonas reinhardtii mediated by the cell penetrating peptide pVEC (LLIILRRRIRKQAHAHSK) which is in a non-covalent form. Using this technically simple method, the ribonucleoprotein was successfully delivered into C. reinhardtii. Gene Maa7 and FKB12 were disrupted, and their distinguishing patterns of Indel mutations were analyzed with the observation of several insertions of sequences not originating from the genome DNA, such as chloroplast DNA, into the expected loci. In addition, the cytotoxicity of Cas9 and the ribonucleoprotein was investigated according to the concentration and time in the algal cells. It was observed that Cas9 alone without the sgRNA induces a more severe cytotoxicity compared to the ribonucleoprotein. Our study will not only contribute to algal cell biology and its genetic engineering for further applications involving various organisms but will also provide a deeper understating of the basic science of the CRISPR/Cas9 system.
Quantitative material analysis using secondary electron energy spectromicroscopy
Authors: Han W. , Zheng M. , Banerjee A. , Luo Y. Z. , Shen L. , Khursheed A.
Published: December 2020

This paper demonstrates how secondary electron energy spectroscopy (SEES) performed inside a scanning electron microscope (SEM) can be used to map sample atomic number and acquire bulk valence band density of states (DOS) information at low primary beam voltages. The technique uses an electron energy analyser attachment to detect small changes in the shape of the scattered secondary electron (SE) spectrum and extract out fine structure features from it. Close agreement between experimental and theoretical bulk valance band DOS distributions was obtained for six different test samples, where the normalised root mean square deviation ranged from 2.7 to 6.7%. High accuracy levels of this kind do not appear to have been reported before. The results presented in this paper point towards SEES becoming a quantitative material analysis companion tool for low voltage scanning electron microscopy (LVSEM) and providing new applications for Scanning Auger Microscopy (SAM) instruments.
Fabrication and characterization of mechanically competent 3D printed polycaprolactone-reduced graphene oxide scaffolds
Authors: Seyedsalehi Amir , Daneshmandi Leila , Barajaa Mohammed , Riordan John , Laurencin Cato T.
Published: December 2020

The ability to produce constructs with a high control over the bulk geometry and internal architecture has situated 3D printing as an attractive fabrication technique for scaffolds. Various designs and inks are actively investigated to prepare scaffolds for different tissues. In this work, we prepared 3D printed composite scaffolds comprising polycaprolactone (PCL) and various amounts of reduced graphene oxide (rGO) at 0.5, 1, and 3 wt.%. We employed a two-step fabrication process to ensure an even mixture and distribution of the rGO sheets within the PCL matrix. The inks were prepared by creating composite PCL-rGO films through solvent evaporation casting that were subsequently fed into the 3D printer for extrusion. The resultant scaffolds were seamlessly integrated, and 3D printed with high fidelity and consistency across all groups. This, together with the homogeneous dispersion of the rGO sheets within the polymer matrix, significantly improved the compressive strength and stiffness by 185% and 150%, respectively, at 0.5 wt.% rGO inclusion. The in vitro response of the scaffolds was assessed using human adipose-derived stem cells. All scaffolds were cytocompatible and supported cell growth and viability. These mechanically reinforced and biologically compatible 3D printed PCL-rGO scaffolds are a promising platform for regenerative engineering applications.
pH-controlled stacking direction of the β-strands in peptide fibrils
Authors: Tseng Wei-Hsuan , Chen Szu-Hua , Hiramatsu Hirotsugu
Published: December 2020

Peptides provide a framework for generating functional biopolymers. In this study, the pH-dependent structural changes in the 21–29 fragment peptide of β2-microglobulin (β2m21–29) during self-aggregation, i.e., the formation of an amyloid fibril, were discussed. The β-sheet structures formed during parallel stacking under basic conditions (pH ≥ 7.7) adopted an anti-parallel stacking configuration under acidic conditions (pH ≤ 7.6). The parallel and anti-parallel β-sheets existed separately at the intermediate pH (pH = 7.6–7.7). These results were attributed to the rigidity of the β-sheets in the fibrils, which prevented the stable hydrogen bonding interactions between the parallel and anti-parallel β-sheet moieties. This observed pH dependence was ascribed to two phenomena: (i) the pH-dependent collapse of the β2m21–29 fibrils, which consisted of 16 ± 3 anti-parallel β-sheets containing a total of 2000 β-strands during the deprotonation of the NH3+ group (pKa = 8.0) of the β-strands that occurred within 0.7 ± 0.2 strands of each other and (ii) the subsequent formation of the parallel β-sheets. We propose a framework for a functional biopolymer that could alternate between the two β-sheet structures in response to pH changes.
Theoretical basis for the use of non-invasive thermal measurements to assess the brain injury in newborns undergoing therapeutic hypothermia
Authors: Walas Wojciech , Bandoła Dominika , Ostrowski Ziemowit , Rojczyk Marek , Mączko Anna , Halaba Zenon , Nowak Andrzej J.
Published: December 2020

The aim of this paper is to propose a new non-invasive methodology to estimate thermogenesis in newborns with perinatal asphyxia (PA) undergoing therapeutic hypothermia (TH). Metabolic heat production (with respect to either a neonate’s body mass or its body surface) is calculated from the newborn’s heat balance, estimating all remaining terms of this heat balance utilising results of only non-invasive thermal measurements. The measurement devices work with standard equipment used for therapeutic hypothermia and are equipped with the Global System for Mobile Communications (GSM), which allows one to record and monitor the course of the therapy remotely (using an internet browser) without disturbing the medical personnel. This methodology allows one to estimate thermogenesis in newborns with perinatal asphyxia undergoing therapeutic hypothermia. It also offers information about instantaneous values of the rate of cooling together with values of remaining rates of heat transfer. It also shows the trend of any changes, which are recorded during treatment. Having information about all components of the heat balance one is able to facilitate comparison of results obtained for different patients, in whom these components may differ. The proposed method can be a new tool for measuring heat balance with the possibility of offering better predictions regarding short-term neurologic outcomes and tailored management in newborns treated by TH.
Probing of heavy metals in the feathers of shorebirds of Central Asian Flyway wintering grounds
Authors: Pandiyan Jeganathan , Jagadheesan Rajendran , Karthikeyan Ganesan , Mahboob Shahid , Al-Ghanim Khalid A. , Al-Misned Fahad , Ahmed Zubair , Krishnappa Kaliyamoorthy , Elumalai Kuppusamy , Govindarajan Marimuthu
Published: December 2020

The study is intended to deliver the incidence of heavy metals in the feathers of shorebirds from two important Central Asian Flyway (CAF) migratory shorebirds wintering sites such as the Point Calimere Wildlife Sanctuary (PWLS) and Pichavaram Mangrove Forest (PMF), India. Feathers of fifteen species of shorebirds and seven different metals viz., Cu, Cr, Co, Pb, Hg, Ni and Zn were analyzed. Zn was highest in Dunlin, Little-ringed Plover, Marsh Sandpiper, and Common sandpiper, Ni showed highest in Little ringed plover, and Common sandpiper, Co, Cr, and Cu were maximum in Little stint, Marsh sandpiper, and Dunlin, respectively. The Hg was higher in Black-winged stilt, Common redshank, Curlew Sandpiper, Eurasian curlew, Lesser Sand-plover, Temminck’s stint, Kentish plover, Spotted redshank, and Wood sandpiper, the Pb found highest in Kentish plover, Painted stork, Spotted redshank, Wood sandpiper, Eurasian Curlew, and Lesser sand-plover. The concentration of metals showed significant variations among the species of shorebirds studied (P < 0.001). The mercury negatively correlated with the other metals than the other six metals studied in both the wetlands. The order of metal concentration in the feathers of shorebirds was Zn > Ni > Co > Cr > Cu > Pb > Hg. Nevertheless, the current study revealed that the level of metals in the shorebirds is alarming; since the PWLS and PMF are located along the CAF routes, it needs intensive studies on various pollutions to manage both the resident as well as migratory shorebirds.
Reference gene selection for transcriptional profiling in Cryptocercus punctulatus, an evolutionary link between Isoptera and Blattodea
Authors: Li Zhen , Li Xiangrui , Zhang Qingwen , Yuan Ling , Zhou Xuguo
Published: December 2020

The subsocial life style and wood-feeding capability of Cryptocercus gives us an evolutionary key to unlock some outstanding questions in biology. With the advent of the Genomics Era, there is an unprecedented opportunity to address the evolution of eusociality and the acquisition of lignocellulases at the genetic level. However, to quantify gene expression, an appropriate normalization strategy is warranted to control for the non-specific variations among samples across different experimental conditions. To search for the internal references, 10 housekeeping genes from a gut transcriptome of a wood-feeding cockroach, Cryptocercus punctulatus, were selected as the candidates for the RT-qPCR analysis. The expression profiles of these candidates, including ACT, EF1α, GAPDH, HSP60, HSP70, αTUB, UBC, RPS18, ATPase and GST, were analyzed using a panel of analytical tools, including geNorm, NormFinder, BestKeeper, and comparative ΔCT method. RefFinder, a comprehensive ranking system integrating all four above-mentioned algorithms, rated ACT as the most stable reference gene for different developmental stages and tissues. Expression analysis of the target genes, Hex-1 and Cell-1, using the most or the least appropriate reference genes and a single or multiple normalizers signified this research. Our finding is the first step toward establishing a standardized RT-qPCR analysis in Cryptocercus.
Serum amyloid A is a positive acute phase protein in Russian sturgeon challenged with Aeromonas hydrophila
Authors: Castellano Mauricio , Silva-Álvarez Valeria , Aversa-Marnai Marcio , Lamas-Bervejillo María , Quartiani Ignacio , Perretta Alejandro , Villarino Andrea , Ferreira Ana María
Published: December 2020

The immune system of sturgeons, one of the most ancient and economically valuable fish worldwide, is poorly understood. The lack of molecular tools and data about infection biomarkers hinders the possibility to monitor sturgeon health during farming and detect infection outbreaks. To tackle this issue, we mined publicly available transcriptomic datasets and identified putative positive acute-phase proteins (APPs) of Russian sturgeons that could be induced by a bacterial infection and monitored using non-invasive methods. Teleost literature compelled us to focus on five promising candidates: hepcidin, a warm acclimation associated hemopexin, intelectin, serum amyloid A protein (SAA) and serotransferrin. Among them, SAA was the most upregulated protein at the mRNA level in the liver of sturgeons challenged with heat-inactivated or liveAeromonas hydrophila. To assess whether this upregulation yielded increasing SAA levels in circulation, we developed an in-house ELISA to quantify SAA levels in sturgeon serum. Circulating SAA rose upon bacterial challenge and positively correlated with hepaticsaaexpression. This is the first time serum SAA has been quantified in an Actinopterygii fish. Since APPs vary across different fish species, our work sheds light on sturgeon acute-phase response, revealing that SAA is a positive APP with potential value as infection biomarker.
Population pharmacokinetic analysis of doripenem for Japanese patients in intensive care unit
Authors: Nonoshita Ko , Suzuki Yosuke , Tanaka Ryota , Kaneko Tetsuya , Ohchi Yoshifumi , Sato Yuhki , Yasuda Norihisa , Goto Koji , Kitano Takaaki , Itoh Hiroki
Published: December 2020

We aimed to construct a novel population pharmacokinetics (PPK) model of doripenem (DRPM) for Japanese patients in intensive care unit, incorporating the clearance of DRPM by continuous renal replacement therapy (CRRT). Twenty-one patients treated with DRPM (0.25 or 0.5 g) by intravenous infusion over 1 h were included in the study. Nine of the 21 patients were receiving CRRT. Plasma samples were obtained before and 1, 2, 4, 6 and 8 h after the first DRPM administration. PPK analysis was conducted by nonlinear mixed effects modeling using a two-compartment model. Total clearance (CLtotal) in the model was divided into CRRT clearance (CLCRRT) and body clearance (CLbody). The final model was: CLtotal (L h−1) = CLbody(non-CRRT) = 3.65 × (Ccr/62.25)0.64 in the absence of CRRT, or = CLbody(CRRT) + CLCRRT = 2.49 × (Ccr/52.75)0.42 + CLCRRT in the presence of CRRT; CLCRRT = QE × 0.919 (0.919 represents non-protein binding rate of DRPM); V1 (L) = 10.04; V2 (L) = 8.13; and Q (L h−1) = 3.53. Using this model, CLtotal was lower and the distribution volumes (V1 and V2) tended to be higher compared to previous reports. Also, Ccr was selected as a significant covariate for CLbody. Furthermore, the contribution rate of CLCRRT to CLtotal was 30–40%, suggesting the importance of drug removal by CRRT. The population analysis model used in this study is a useful tool for planning DRPM regimen and administration. Our novel model may contribute greatly to proper use of DRPM in patients requiring intensive care.
Selenization of S. cerevisiae increases its protective potential in experimental autoimmune encephalomyelitis by triggering an intestinal immunomodulatory loop
Authors: de Campos Fraga-Silva Thais Fernanda , Mimura Luiza Ayumi Nishiyama , de Oliveira Larissa Ragozo Cardoso , dos Santos Toledo Juliana Helena , Borim Patrícia Aparecida , Zorzella-Pezavento Sofia Fernanda Gonçalvez , Alonso Diego Peres , Ribolla Paulo Eduardo Martins , de Oliveira Carlos Alberto Ferreira , da Fonseca Denise Morais , Villablanca Eduardo J. , Sartori Alexandrina
Published: December 2020

Multiple sclerosis is an autoimmune disease that affects the myelinated central nervous system (CNS) neurons and triggers physical and cognitive disabilities. Conventional therapy is based on disease-modifying drugs that control disease severity but can also be deleterious. Complementary medicines have been adopted and evidence indicates that yeast supplements can improve symptoms mainly by modulating the immune response. In this investigation, we evaluated the therapeutic potential of Saccharomyces cerevisiae and its selenized derivative (Selemax) in experimental autoimmune encephalomyelitis (EAE). Female C57BL/6 mice submitted to EAE induction were orally supplemented with these yeasts by gavage from day 0 to day 14 after EAE induction. Both supplements determined significant reduction in clinical signs concomitantly with diminished Th1 immune response in CNS, increased proportion of Foxp3+ lymphocytes in inguinal and mesenteric lymph nodes and increased microbiota diversity. However, Selemax was more effective clinically and immunologically; it reduced disease prevalence more sharply, increased the proportion of CD103+ dendritic cells expressing high levels of PD-L1 in mesenteric lymph nodes and reduced the intestinal inflammatory process more strongly than S. cerevisiae. These results suggest a clear gut-brain axis modulation by selenized S. cerevisiae and suggest their inclusion in clinical trials.
DNA damage in human glomerular endothelial cells induces nodular glomerulosclerosis via an ATR and ANXA2 pathway
Authors: Fujii Ai , Sunatani Yumi , Furuichi Kengo , Fujimoto Keiji , Adachi Hiroki , Iwabuchi Kuniyoshi , Yokoyama Hitoshi
Published: December 2020

Collagen type VI (COL6) deposition occurs in various glomerular diseases, causing serious pathological damage like nodular lesions. However, the mechanisms underlying the deposition of COL6 remain unclear. In renal biopsy samples, immunohistochemical analyses revealed that COL6 and phosphorylated histone H2AX (γ-H2AX), a DNA damage marker, were detected mainly in diabetic nodular glomerulosclerosis, in which the γ-H2AX-positive area was identified as the independent factor significantly associated with the COL6-positive area (β: 0.539, t = 2.668). In in vitro studies, COL6 secretion from human renal glomerular endothelial cells (HRGECs) was assessed by measuring the decrease in the cytoplasmic COL6-positive cells and an increase in the amount of COL6 in the culture medium. Mitomycin C (MMc) treatment of HRGECs increased the number of γ-H2AX-positive cells and COL6 secretion, which were suppressed by a specific inhibitor of ataxia telangiectasia and Rad3-related (ATR). MMc-induced COL6 secretion was also suppressed by Annexin A2 (ANXA2) siRNA transfection. Moreover, the inhibition of ATR activity did not induce any extra suppression in the MMc-induced COL6 secretion by ANXA2 siRNA transfected cells. These results confirm that nodular glomerulosclerosis partially results from DNA damage in the glomerulus and that DNA damage-induced COL6 secretion from HRGECs occurs through an ATR and ANXA2-mediated pathway.
Long-term memory guides resource allocation in working memory
Authors: Bruning Allison L. , Lewis-Peacock Jarrod A.
Published: December 2020

Working memory capacity is incredibly limited and thus it is important to use this resource wisely. Prior knowledge in long-term memory can aid in efficient encoding of information by allowing for the prioritization of novel stimuli over familiar ones. Here we used a full-report procedure in a visual working memory paradigm, where participants reported the location of six colored circles in any order, to examine the influence of prior information on resource allocation in working memory. Participants learned that one of the items appeared in a restricted range of locations, whereas the remaining items could appear in any location. We found that participants’ memory performance benefited from learning this prior information. Specifically, response precision increased for all items when prior information was available for one of the items. Responses for both familiar and novel items were systematically ordered from highest to lowest precision. Participants tended to report the familiar item in the second half of the six responses and did so with greater precision than for novel items. Moreover, novel items that appeared near the center of the prior location were reported with worse precision than novel items that appeared elsewhere. This shows that people strategically allocated working memory resources by ignoring information that appeared in predictable locations and prioritizing the encoding of information that appeared in unpredictable locations. Together these findings demonstrate that people rely on long-term memory not only for remembering familiar items, but also for the strategic allocation of their limited capacity working memory resources.
Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models
Authors: Horiai Machi , Otsuka Ayano , Hidema Shizu , Hiraoka Yuichi , Hayashi Ryotaro , Miyazaki Shinji , Furuse Tamio , Mizukami Hiroaki , Teruyama Ryoichi , Tamura Masaru , Bito Haruhiko , Maejima Yuko , Shimomura Kenju , Nishimori Katsuhiko
Published: December 2020

Autism spectrum disorder (ASD) is a continuum of neurodevelopmental disorders and needs new therapeutic approaches. Recently, oxytocin (OXT) showed potential as the first anti-ASD drug. Many reports have described the efficacy of intranasal OXT therapy to improve the core symptoms of patients with ASD; however, the underlying neurobiological mechanism remains unknown. The OXT/oxytocin receptor (OXTR) system, through the lateral septum (LS), contributes to social behavior, which is disrupted in ASD. Therefore, we selectively express hM3Dq in OXTR-expressing (OXTR+) neurons in the LS to investigate this effect in ASD mouse models developed by environmental and genetic cues. In mice that received valproic acid (environmental cue), we demonstrated successful recovery of impaired social memory with three-chamber test after OXTR+ neuron activation in the LS. Application of a similar strategy to Nl3R451C knock-in mice (genetic cue) also caused successful recovery of impaired social memory in single field test. OXTR+ neurons in the LS, which are activated by social stimuli, are projected to the CA1 region of the hippocampus. This study identified a candidate mechanism for improving core symptoms of ASD by artificial activation of DREADDs, as a simulation of OXT administration to activate OXTR+ neurons in the LS.
Dynamic survival prediction in intensive care units from heterogeneous time series without the need for variable selection or curation
Authors: Deasy Jacob , Liò Pietro , Ercole Ari
Published: December 2020

Extensive monitoring in intensive care units (ICUs) generates large quantities of data which contain numerous trends that are difficult for clinicians to systematically evaluate. Current approaches to such heterogeneity in electronic health records (EHRs) discard pertinent information. We present a deep learning pipeline that uses all uncurated chart, lab, and output events for prediction of in-hospital mortality without variable selection. Over 21,000 ICU patients and tens of thousands of variables derived from the MIMIC-III database were used to train and validate our model. Recordings in the first few hours of a patient’s stay were found to be strongly predictive of mortality, outperforming models using SAPS II and OASIS scores, AUROC 0.72 and 0.76 at 24 h respectively, within just 12 h of ICU admission. Our model achieves a very strong predictive performance of AUROC 0.85 (95% CI 0.83–0.86) after 48 h. Predictive performance increases over the first 48 h, but suffers from diminishing returns, providing rationale for time-limited trials of critical care and suggesting that the timing of decision making can be optimised and individualised.
Low oxygen levels caused by Noctiluca scintillans bloom kills corals in Gulf of Mannar, India
Authors: Raj K. Diraviya , Mathews G. , Obura David O. , Laju R. L. , Bharath M. Selva , Kumar P. Dinesh , Arasamuthu A. , Kumar T. K. Ashok , Edward J. K. Patterson
Published: December 2020

Coral reefs around the world are undergoing severe decline in the past few decades. Mass coral mortalities have predominantly been reported to be caused by coral bleaching or disease outbreaks. Temporary hypoxic conditions caused by algal blooms can trigger mass coral mortalities though are reported rarely. In this study in Gulf of Mannar (GoM), southeast India, we report a significant coral mortality caused by a bloom of the ciguatoxic dinoflagellate Noctiluca scintillans during September–October 2019. Dissolved oxygen levels declined below 2 mg l−1 during the bloom causing temporary hypoxia and mortality (up to 71.23%) in the fast growing coral genera Acropora, Montipora and Pocillopora. Due to global climate change, more frequent and larger algal blooms are likely in the future. Hence, it is likely that shallow water coral reefs will be affected more frequently by episodic hypoxic conditions driven by algal blooms. More studies are, however, required to understand the mechanism of coral mortality due to algal blooms, impacts on community composition and the potential for subsequent recovery.
Unrepaired decompressive craniectomy worsens motor performance in a rat traumatic brain injury model
Authors: Andrews Brian T. , Barbay Scott , Townsend Jakob , Detamore Michael , Harris Janna , Tuchek Chad , Nudo Randolph J.
Published: December 2020

Decompressive craniectomy (DC) is often required to manage rising intracranial pressure after traumatic brain injury (TBI). Syndrome of the trephine (SoT) is a reversible neurologic condition that often occurs following DC as a result of the unrepaired skull. The purpose of the present study is to characterize neurological impairment following TBI in rats with an unrepaired craniectomy versus rats with a closed cranium. Long Evans male rats received a controlled cortical impact (CCI) over the caudal forelimb area (CFA) of the motor cortex. Immediately after CCI, rats received either a hemi-craniectomy (TBI Open Skull Group) or an immediate acrylic cranioplasty restoring cranial anatomy (TBI Closed Skull Group). Motor performance was assessed on a skilled reaching task on post-CCI weeks 1—4, 8, 12, and 16. Three weeks after the CCI injury, the TBI Closed Skull Group demonstrated improved motor performance compared to TBI Open Skull Group. The TBI Closed Skull Group continued to perform better than the TBI Open Skull Group throughout weeks 4, 8, 12 and 16. The protracted recovery of CFA motor performance demonstrated in rats with unrepaired skulls following TBI suggests this model may be beneficial for testing new therapeutic approaches to prevent SoT.
Experimental evidence for yawn contagion in orangutans (Pongo pygmaeus)
Authors: van Berlo Evy , Díaz-Loyo Alejandra P. , Juárez-Mora Oscar E. , Kret Mariska E. , Massen Jorg J. M.
Published: December 2020

Yawning is highly contagious, yet both its proximate mechanism(s) and its ultimate causation remain poorly understood. Scholars have suggested a link between contagious yawning (CY) and sociality due to its appearance in mostly social species. Nevertheless, as findings are inconsistent, CY’s function and evolution remains heavily debated. One way to understand the evolution of CY is by studying it in hominids. Although CY has been found in chimpanzees and bonobos, but is absent in gorillas, data on orangutans are missing despite them being the least social hominid. Orangutans are thus interesting for understanding CY’s phylogeny. Here, we experimentally tested whether orangutans yawn contagiously in response to videos of conspecifics yawning. Furthermore, we investigated whether CY was affected by familiarity with the yawning individual (i.e. a familiar or unfamiliar conspecific and a 3D orangutan avatar). In 700 trials across 8 individuals, we found that orangutans are more likely to yawn in response to yawn videos compared to control videos of conspecifics, but not to yawn videos of the avatar. Interestingly, CY occurred regardless of whether a conspecific was familiar or unfamiliar. We conclude that CY was likely already present in the last common ancestor of humans and great apes, though more converging evidence is needed.