bluuebunny/crossref_metadata_2025 huggingface dataset:
A theoretical framework for multi-species range expansion in spatially heterogeneous landscapes
Authors: Eigentler Lukas , Stanley-Wall Nicola R. , Davidson Fordyce A.
Published: November 2021

Range expansion is the spatial spread of a population into previously unoccupied regions. Understanding range expansion is important for the study and successful manipulation and management of ecosystems, with applications ranging from controlling bacterial biofilm formation in industrial and medical environments to large scale conservation programmes for species undergoing climate-change induced habitat disruption. During range expansion, species typically encounter competitors. Moreover, the environment into which expansion takes place is almost always heterogeneous when considered at the scale of the individual. Despite the ubiquitous nature of these features, the impact of competition and spatial landscape heterogeneities on range expansion remains understudied. In this paper we present a theoretical framework comprising two competing generic species undergoing range expansion and use it to investigate the impact of spatial landscape heterogeneities on range expansion with a particular focus on its effect on competition dynamics. We reveal that the area covered by range expansion during a fixed time interval is highly variable due to the fixed landscape heterogeneities. Moreover, we report significant variability in competitive outcome (relative abundance of a focal species) but determine that this is induced by low initial population densities, independent of landscape heterogeneities. We further show that both area covered by range expansion and competitive outcome can be accurately predicted by a Voronoi tessellation with respect to an appropriate metric, which only requires information on the spatial landscape and the response of each species to that landscape. Finally, we reveal that if species interact antagonistically during range expansion, the dominant mode of competition depends on the initial population density. Antagonistic actions determine competitive outcome if the initial population density is high, but competition for space is the dominant mode of competition if the initial population density is low.
Neurons from individual early Alzheimer’s disease patients reflect their clinical vulnerability
Authors: Ng Bryan , Rowland Helen A. , Wei Tina , Arunasalam Kanisa , Hayes Emma Mee , Koychev Ivan , Hedegaard Anne , Ribe Elena M. , Chan Dennis , Chessell Tharani , ffytche Dominic , Gunn Roger N. , Kocagoncu Ece , Lawson Jennifer , Malhotra Paresh , Ridha Basil H. , Rowe James B. , Thomas Alan J. , Zamboni Giovanna , Buckley Noel J. , Cader Zameel M. , Lovestone Simon , Wade-Martins Richard
Published: November 2021

Establishing preclinical models of Alzheimer’s disease that predict clinical outcomes remains a critically important, yet to date not fully realised, goal. Models derived from human cells offer considerable advantages over non-human models, including the potential to reflect some of the inter-individual differences that are apparent in patients. Here we report an approach using induced pluripotent stem cell-derived cortical neurons from people with early symptomatic Alzheimer’s disease where we sought a match between individual disease characteristics in cells with analogous characteristics in the people from whom they were derived. We show that the response to amyloid-β burden in life, as measured by cognitive decline and brain activity levels, varies between individuals and this vulnerability rating correlates with the individual cellular vulnerability to extrinsic amyloid-β in vitro as measured by synapse loss and function. Our findings indicate that patient induced pluripotent stem cell-derived cortical neurons not only present key aspects of Alzheimer’s disease pathology, but also reflect key aspects of the clinical phenotypes of the same patients. Cellular models that reflect an individual’s in-life clinical vulnerability thus represent a tractable method of Alzheimer’s disease modelling using clinical data in combination with cellular phenotypes.
Identification of mRNAs that undergo stop codon readthrough inArabidopsis thaliana
Authors: Sahoo Sarthak , Singh Divyoj , Singh Anumeha , Eswarappa Sandeep M
Published: November 2021

A stop codon ensures termination of translation at a specific position on an mRNA. Sometimes, termination fails as translation machinery recognizes a stop codon as a sense codon. This leads to stop codon readthrough (SCR) resulting in the continuation of translation beyond the stop codon, generating protein isoforms with C-terminal extension. SCR has been observed in viruses, fungi, and multicellular organisms including mammals. However, SCR is largely unexplored in plants. In this study, we have analyzed ribosome profiling datasets to identify mRNAs that undergo SCR inArabidopsis thaliana. Analyses of the ribosome density, ribosome coverage and three-nucleotide periodicity of the ribosome profiling reads, in the mRNA region downstream of the stop codon, provided strong evidence for SCR in mRNAs of 144 genes. This process generates putative peroxisomal targeting signal, nuclear localization signal, prenylation signal, transmembrane helix and intrinsically disordered regions in the C-terminal extension of several of these proteins. Gene ontology (GO) functional enrichment analysis revealed that these 144 genes belong to three major functional groups - translation, photosynthesis and abiotic stress tolerance. Finally, using a luminescence-based assay, we experimentally demonstrate SCR in representative mRNAs belonging to these functional classes. Based on these observations, we propose that SCR plays an important role in plant physiology by regulating the protein localization and function.

AUTHOR SUMMARY

Protein synthesis executed by macromolecular complexes, termed ribosomes, starts and stops at specific locations on a messenger RNA (mRNA). This fidelity is critical for the normal functioning of cells. However, sometimes ribosomes don’t stop translation at the stop signal (termed stop codon) on an mRNA resulting in longer proteins with properties different from those of the canonical shorter protein. This process called stop codon readthrough (SCR) has been observed in viruses, fungi, and multicellular organisms including mammals. However, it remains largely unexplored in plants. In this study, we report evidence of SCR in 144 genes ofArabidopsis thaliana, a small flowering weed widely used as a model system to study plant biology. These genes are involved in protein synthesis, photosynthesis and stress tolerance in plants. We have also experimentally demonstrated SCR in a few genes that represent these functional classes. Our analysis shows that SCR can change the localization and functional properties of these proteins. We propose that SCR plays an important role in plant physiology.
Fast anther dehiscence state recognition system establishing by deep learning to screen heat tolerant cotton
Authors: Tan Zhihao , Shi Jiawei , Lv Rongjie , Li Qingyuan , Yang Jing , Ma Yizan , Li Yanlong , Wu Yuanlong , Zhang Rui , Ma Huanhuan , Li Yawei , Zhu Li , Kong Jie , Zhang Xianlong , Yang Wanneng , Min Ling
Published: November 2021

Cotton is one of the most economically important crops in the world. The fertility of male reproductive organs is a key determinant of cotton yield. The anther dehiscence or indehiscence directly determine the probability of fertilization in cotton. Thus, the rapid and accurate identification of cotton anther dehiscence status is important for judging anther growth status and promoting genetic breeding research. The development of computer vision technology and the advent of big data have prompted the application of deep learning techniques to agricultural phenotype research. Therefore, two deep learning models (Faster R-CNN and YOLOv5) were proposed to detect the number and dehiscence status of anthers. The single-stage model based on YOLOv5 has higher recognition efficiency and the ability to deploy to the mobile end. Breeding researchers can apply this model to terminals to achieve a more intuitive understanding of cotton anther dehiscence status. Moreover, three improvement strategies of Faster R-CNN model were proposed, the improved model has higher detection accuracy than YOLOv5 model. In addition, the percentage of dehiscent anther of randomly selected 30 cotton varieties were observed from cotton population under normal temperature and high temperature (HT) conditions through the integrated Faster R-CNN model and manual observation. The result showed HT varying decreased the percentage of dehiscent anther in different cotton lines, consistent with the manual method. Thus, this system can help us to rapid and accurate identification of HT-tolerant cotton.

One sentence summary

The deep learning technique was applied to identify the anther dehiscence state for the first time to quickly screen heat tolerant cotton varieties and help to explore key genetic improvement genes.
NIfTI-MRS: A standard format for magnetic resonance spectroscopic data
Authors: Clarke William T , Mikkelsen Mark , Oeltzschner Georg , Bell Tiffany K. , Shamaei Amirmohammad , Soher Brian J. , Emir Uzay E , Wilson Martin
Published: November 2021

Purpose

The use of multiple data formats in the MRS community currently hinders data sharing and integration. NIfTI-MRS is proposed as a standard MR spectroscopy data format, which is implemented as an extension to the neuroimaging informatics technology initiative (NIfTI) format.

Using this standardised format will facilitate data sharing, ease algorithm development, and encourage the integration of MRS analysis with other imaging modalities.

Methods

A file format based on the NIfTI header extension framework was designed to incorporate essential spectroscopic metadata and additional encoding dimensions. A detailed description of the specification is provided. An open-source command-line conversion program is implemented to enable conversion of single-voxel and spectroscopic imaging data to NIfTI-MRS. To provide visualisation of data in NIfTI-MRS, a dedicated plugin is implemented for FSLeyes, the FSL image viewer.

Results

Alongside online documentation, ten example datasets are provided in the proposed format. In addition, minimal examples of NIfTI-MRS readers have been implemented. The conversion software, spec2nii, currently converts fourteen formats to NIfTI-MRS, including DICOM and vendor proprietary formats.

Conclusion

The proposed format aims to solve the issue of multiple data formats being used in the MRS community. By providing a single conversion point, it aims to simplify the processing and analysis of MRS data, thereby lowering the barrier to use of MRS. Furthermore, it can serve as the basis for open data sharing, collaboration, and interoperability of analysis programs. It also opens possibility of greater standardisation and harmonisation. By aligning with the dominant format in neuroimaging, NIfTI-MRS enables the use of mature tools present in the imaging community, demonstrated in this work by using a dedicated imaging tool, FSLeyes, as a viewer.
Oversized cells activate global proteasome-mediated protein degradation to maintain cell size homeostasis
Authors: Liu Shixuan , Tan Ceryl , Melo-Gavin Chloe , Ginzberg Miriam B. , Blutrich Ron , Patel Nish , Rape Michael , Mark Kevin G. , Kafri Ran
Published: November 2021

Proliferating animal cells maintain a stable size distribution over generations despite fluctuations in cell growth and division size. This tight control of cell size involves both cell size checkpoints, which delay cell cycle progression in small cells, and size-dependent regulation of mass accumulation rates. While we previously identified the p38 MAPK pathway as a key regulator of the mammalian cell size checkpoint, the mechanism of size-dependent growth rate regulation has remained elusive. Here, we quantified global rates of protein synthesis and degradation in cells of varying sizes, both under unperturbed conditions and in response to perturbations that trigger size-dependent compensatory growth slowdown. We found that protein synthesis rates scale proportionally with cell size across cell cycle stages and experimental conditions. In contrast, oversized cells that undergo compensatory growth slowdown exhibit a superlinear increase in proteasome-mediated protein degradation, with accelerated protein turnover per unit mass, suggesting activation of the proteasomal degradation pathway. Both nascent and long-lived proteins contribute to the elevated protein degradation during compensatory growth slowdown, with long-lived proteins playing a crucial role at the G1/S transition. Notably, large G1/S cells exhibit particularly high efficiency in protein degradation, surpassing that of similarly sized or larger cells in S and G2, coinciding with the timing of the most stringent size control in animal cells. These results collectively suggest that oversized cells reduce their growth efficiency by activating global proteasome-mediated protein degradation to promote cell size homeostasis.
Prehension Kinematics in Humans and Macaques
Authors: Yan Yuke , Sobinov Anton R. , Bensmaia Sliman J.
Published: November 2021

Abstract

Non-human primates, especially rhesus macaques, have been a dominant model to study sensorimotor control of the upper limbs. Indeed, human and macaques have similar hands and homologous neural circuits to mediate manual behavior. However, few studies have systematically and quantitatively compared the manual behaviors of the two species. Such comparison is critical for assessing the validity of using the macaque sensorimotor system as a model of its human counterpart. In this study, we systematically compared the prehensile behaviors of humans and rhesus macaques using an identical experimental setup. We found human and macaque prehension kinematics to be generally similar with a few subtle differences. While the structure of the preshaping postures is similar in humans and macaques, human postures are more object-specific and human joints are less intercorrelated. Conversely, monkeys demonstrate more stereotypical grasping behaviors that are common across all grasp conditions and more variability in their postures across repeated grasps of the same object. Despite these subtle differences in manual behavior between humans and monkeys, our results bolster the use of the macaque model to understand the neural mechanisms of manual dexterity in humans.

New and newsworthy

Macaques have been a dominant animal model to study the neural mechanisms of human dexterity because they exhibit complex manual behavior. We show that the kinematics of prehension – a critical dexterous behavior – are largely similar in humans and macaques. However, human preshaping postures are more object-specific and the movement of human digits are less correlated with each other. The thumb, index, and wrist are major driver of these interspecies differences.
Control of cortical cytoskeleton-membrane interaction by RhoA regulates peripheral nerve myelination
Authors: Seixas Ana I. , Morais Miguel R. G. , Brakebusch Cord , Relvas João B.
Published: November 2021

Bidirectional transmission of mechanical and biochemical signals is integral to cell-environment communication and underlies the function of Schwann cells, the myelinating glia of the peripheral nervous system. As major integrators of “outside-in” signaling, Rho GTPases link actin cytoskeleton dynamics with cellular architecture to regulate adhesion and cell deformation. Using Schwann cell-specific gene inactivation, we discovered that RhoA promotes the initiation of myelination, axonal wrapping and axial spreading of Schwann cells, and is later required to restrict myelin growth in peripheral nerves. These effects are mediated by modulation of actomyosin contractility, actin dynamics and cortical actin-membrane attachment, which collectively couple tensional forces to intracellular signaling that regulate axon-Schwann cell interaction and myelin synthesis. This work establishes RhoA as an intrinsic regulator of a biomechanical response that controls the switch of Schwann cells towards the myelinating and the homeostatic states.
On-tissue spatial proteomics integrating MALDI-MS imaging with shotgun proteomics reveals soy consumption-induced biomarkers in a fragile X syndrome mouse model
Authors: Ma Min , Yu Qinying , Delafield Daniel G. , Cui Yusi , Li Zihui , Wu Wenxin , Shi Xudong , Gutierrez Alejandra , Westmark Pamela R. , Xu Meng , Westmark Cara J. , Li Lingjun
Published: November 2021

Soy-based diets are associated with increased seizures and autism. Thus, there is an acute need for unbiased protein biomarker identification in Fragile X syndrome (FXS) in response to soy consumption. Herein, we present a spatial proteomics approach integrating mass spectrometry imaging (MSI) with label-free proteomics in a mouse model of FXS to map the spatial distribution and quantify the levels of proteins in the hippocampus and hypothalamus brain regions. In total, 1,004 unique peptides were spatially resolved, demonstrating the diverse array of peptidomes present in the tissue slices and the broad coverage of the strategy. A group of proteins that are known to be involved in the GABAergic system, synaptic transmission, and co-expression network analysis indicated that protein in soy group was significantly associated with metabolism and synapse modules in the Fmr1KO brain. Ultimately, this spatial proteomics work laid the ground for identifying novel therapeutic targets and biomarkers for FXS.
In silico Analysis of Nonsynonymous Genomic Variants within CCM2 Gene Reaffirm the Existence of Dual Cores within Typical PTB Domain
Authors: Padarti Akhil , Belkin Ofek , Abou-Fadel Johnathan , Zhang Jun
Published: November 2021

Purpose

The objective of this study is to validate the existence of dual cores within the typical phosphotyrosine binding (PTB) domain and to identify potentially damaging and pathogenic nonsynonymous coding single nuclear polymorphisms (nsSNPs) in the canonical PTB domain of the CCM2 gene that causes cerebral cavernous malformations (CCMs).

Methods

The nsSNPs within the coding sequence for PTB domain of human CCM2 gene, retrieved from exclusive database search, were analyzed for their functional and structural impact using a series of bioinformatic tools. The effects of the mutations on tertiary structure of the PTB domain in human CCM2 protein were predicted to examine the effect of the nsSNPs on tertiary structure on PTB Cores.

Results

Our mutation analysis, through alignment of protein structures between wildtype CCM2 and mutant, indicated that the structural impacts of pathogenic nsSNPs is biophysically limited to only the spatially adjacent substituted amino acid site with minimal structural influence on the adjacent core of the PTB domain, suggesting both cores are independently functional and essential for proper CCM2 function.

Conclusion

Utilizing a combination of protein conservation and structure-based analysis, we analyzed the structural effects of inherited pathogenic mutations within the CCM2 PTB domain. Our results indicated that the pathogenic amino acid substitutions lead to only subtle changes locally confined to the surrounding tertiary structure of the PTB core within which it resides, while no structural disturbance to the neighboring PTB core was observed, reaffirming the presence of dual functional cores in the PTB domain.
Quantitative analysis of transcription start site selection inSaccharomyces cerevisiaereveals control by DNA sequence, RNA Polymerase II activity, and NTP levels
Authors: Zhu Yunye , Vvedenskaya Irina O. , Sze Sing-Hoi , Nickels Bryce E. , Kaplan Craig D.
Published: November 2021

Transcription start site (TSS) selection is a key step in gene expression and occurs at many promoter positions over a wide range of efficiencies. Here, we develop a massively parallel reporter assay to quantitatively dissect contributions of promoter sequence, NTP substrate levels, and RNA polymerase II (Pol II) activity to TSS selection by “promoter scanning” inSaccharomyces cerevisiae(Pol II MAssively Systematic Transcript End Readout, “Pol II MASTER”). Using Pol II MASTER, we measure the efficiency of Pol II initiation at 1,000,000 individual TSS sequences in a defined promoter context. Pol II MASTER confirms proposed critical qualities ofS. cerevisiaeTSS -8, -1, and +1 positions quantitatively in a controlled promoter context. Pol II MASTER extends quantitative analysis to surrounding sequences and determines that they tune initiation over a wide range of efficiencies. These results enabled the development of a predictive model for initiation efficiency based on sequence. We show that genetic perturbation of Pol II catalytic activity alters initiation efficiency mostly independently of TSS sequence, but selectively modulates preference for initiating nucleotide. Intriguingly, we find that Pol II initiation efficiency is directly sensitive to GTP levels at the first five transcript positions and to CTP and UTP levels at the second position genome wide. These results suggest individual NTP levels can have transcript-specific effects on initiation, representing a cryptic layer of potential regulation at the level of Pol II biochemical properties. The results establish Pol II MASTER as a method for quantitative dissection of transcription initiation in eukaryotes.
Neutralization breadth of SARS CoV-2 viral variants following primary series and booster SARS CoV-2 vaccines in patients with cancer
Authors: Naranbhai Vivek , Denis Kerri J St. , Lam Evan C , Ofoman Onosereme , Beltran Wilfredo-Garcia , Berrios Cristhian , Bhan Atul K. , Gainor Justin F. , Balazs Alejandro B. , Iafrate A. John
Published: November 2021

Patients with cancer are more likely to have impaired immune responses to SARS CoV-2 vaccines. We studied the breadth of responses against SARS CoV-2 variants followingly primary vaccination in 178 patients with a variety of tumor types, and after booster doses in a subset. Neutralization of alpha, beta, gamma and delta SARS-CoV-2 variants was impaired relative to wildtype (Wuhan), regardless of vaccine type. Regardless of viral variant, mRNA1273 was the most immunogenic, followed by BNT162b2 and then Ad26.COV2.S. Neutralization of more variants (breadth) was associated with higher magnitude of wildtype neutralization, and increase with time since vaccination; increased age associated with lower breadth. Anti-spike binding antibody concentrations were a good surrogate for breadth (PPV=90% at >1000U/ml). Booster SARS-CoV-2 vaccines conferred enhanced breadth. These data suggest that achieving a high antibody titer is desirable to achieve broad neutralization; a single booster dose with current vaccines increases breadth of responses against variants.
Purchasing high-cost medical equipment in hospitals: A systematic review
Authors: Hinrichs-Krapels Saba , Ditewig Bor , Boulding Harriet , Chalkidou Anastasia , Erskine Jamie , Shokraneh Farhad
Published: November 2021

Objectives

To systematically review academic literature for empirical studies on any processes, procedures, methods or approaches to purchasing high-cost medical equipment within hospitals in high-income countries.

Design

Systematic review

Methods

On 13 August 2020, we searched the following from inception: Cost-Effectiveness Analysis Registry, EconLit and ProQuest Dissertations & Theses A&I via ProQuest, Embase, MEDLINE, and MEDLINE in Process via Ovid SP, Google and Google Scholar, Health Management and Policy Database via Ovid SP, IEEE Xplore Digital Library, International HTA Database, NHS EED via CRD Web, Science Citation Index-Expanded, Conference Proceedings Citation Index-Science, and Emerging Sources Citation Index via Web of Science, Scopus, and Zetoc conference search. Studies were included if they described the approach to purchasing (also known as procurement or acquisition) of high-cost medical devices and/or equipment conducting within hospitals in high-income countries between 2000-2020. Studies were screened, data extracted, and summarised.

Results

Of 9437 records, 24 were included, based in 12 different countries and covering equipment types ranging from surgical robots to MRI scanners and orthopaedic implants. Study types included descriptions of processes taking place within or across hospitals (n=14), out of which three reported cost savings; empirical studies in which hospital records or participant data were analysed (n=8), and evaluations or pilots of proposed purchasing processes (n=2). Studies mainly highlight the importance of multidisciplinary involvement (especially clinical engineers and clinicians) in purchasing decision-making to balance technical, financial, safety and clinical aspects of device selection, and the potential of increasing evidence-based decisions using approaches ranging from hospital-based health technology assessments, ergonomics, to conducting user ‘trials’ of the device in use before purchase.

Conclusions

We highlight the lack of rigorous empirical work on this topic, calling for more intervention based and empirical work to advance the evidence base in this domain to advance knowledge, policy and practice.

Strengths and limitations of this study

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First systematic review of empirical work conducted in hospitals on purchasing of high-cost medical devices

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Broad search covering a range of disciplines and study types

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Limited to high-cost equipment which is challenging to differentiate across studies and has no standardised ‘value’ globally
Denoised VEGFR2 expression relates to sunitinib efficacy in advanced Clear Cell Renal Cell Carcinoma
Authors: Verlingue Loïc , Morel Daphné , Schaeffer Mickaël , Tanguy Laurent , Schmidt Jordane , Bernhard Jean-Christophe , Loubaton Bertrand , Bagnard Dominique
Published: November 2021

Short summary

Personalized biomarkers can facilitate decision making upon multiple therapeutic options in ccRCC. VEGFR2 expression denoised with 37 normal and tumor gene-expressions relates to sunitinib effect whereas raw VEGFR2 expression doesn’t relate to sunitinib effect.

Background

Several studies suggested that molecular analysis of patients with advanced clear cell renal cell carcinoma (ccRCC) could indicate whether a patient is susceptible of benefiting from sunitinib in first-line systemic treatment compared to immunotherapies. However, data remain conflicting and no predictive biomarker is validated so far to decipher if sunitinib could still represent a good therapeutic option in first line setting and beyond.

Methods

PREDMED® denoised the tumor RNA expression of 37 genes including KDR (encoding VEGFR2) estimated by RT-qPCR, by normalizing it on the expression of normal kidney tissue and cell types. We investigated the performance of PREDMED® VEGFR2-scoring to predict the clinical effect of sunitinib for patients affected by ccRCC.

Results

Among the 34 ccRCC patients’ samples retrospectively retrieved from the UroCCR project (NCT03293563), high VEGFR2 scores were associated with objective clinical responses under sunitinib treatment and low scores with stable disease or progression with a sensitivity of 86%, a specificity of 67% and an AUC of 72.5% (95%CI[50.1–94.9]; p=0.04). VEGFR2 scores were significantly and positively related to progression-free survival (HR = 0.465; 95%CI[0.221–0.978]; p=0.0311) and overall survival (HR = 0.400; 95%CI[0.192–0.834]; p=0.0134) under sunitinib treatment. In our cohort, raw VEGFR2 expression (before PREDMED® processing) was not related to the above mentioned outcomes.

Conclusion

We describe a gene-expression based algorithm that is accurately related to the effect of sunitinib for patients with ccRCC. We further plan a validation of PREDMED® for combinatorial strategies involving antiangiogenics and immune-checkpoint blockers.
Globally elevated excitation-inhibition ratio in children with autism spectrum disorder and below-average intelligence
Authors: Manyukhina Viktoriya O. , Prokofyev Andrey O. , Galuta Ilia A. , Goiaeva Dzerassa E. , Obukhova Tatiana S. , Schneiderman Justin F. , Altukhov Dmitry I. , Stroganova Tatiana A. , Orekhova Elena V.
Published: November 2021

BACKGROUND

An altered balance of neuronal excitation and inhibition (E-I balance) might be implicated in the co-occurrence of autism and intellectual disability, but this hypothesis has never been tested. E-I balance changes can be estimated from the spectral slope of the aperiodic 1/f neural activity. Herein, we used magnetoencephalography (MEG) to test whether the 1/f slope would differentiate ASD children with and without intellectual disability.

METHODS

MEG was recorded at rest with eyes open/closed in 49 boys with ASD aged 6-15 years with a broad range of IQs, and in 49 age-matched typically developing (TD) boys. The cortical source activity was estimated using the LCMV beamformer approach. We then extracted the 1/f slope by fitting a linear function in to the log-log-scale power spectra in the high-frequency range.

RESULTS

The grand averaged 1/f slope was steeper in the eyes closed than in the eyes open condition, but had high rank-order stability between them. In line with the previous research, the slope flattened with age. Children with ASD and below-average (<85) IQ had flatter slopes than either TD or ASD children with average IQ. These group differences could not be explained by differences in signal-to-noise ratio or periodic (alpha and beta) activity.

CONCLUSIONS

The atypically flattened spectral slope of aperiodic activity in children with ASD and below-average IQ suggests a shift of the global E-I balance toward hyper-excitation. The spectral slope can provide an accessible non-invasive biomarker of the E-I ratio for translational research and making objective judgments about treatment effectiveness.
Children’s Species Literacy as Estimated and Desired by Biodiversity Communicators: a Mismatch with the Actual Level
Authors: Hooykaas Michiel J. D. , Aten Cathelijn , Hemelaar Elisabeth M. , Albers Casper J. , Schilthuizen Menno , Smeets Ionica
Published: November 2021

While biodiversity decline continues and laypeople’s knowledge about species is limited, especially in children, high-quality communication is needed to raise awareness. For this, communicators should be aware of current knowledge levels in their target groups. We compared biodiversity communicators' estimates of the average species literacy level in primary school children with the actual level. Moreover, we explored the importance that communicators placed on species literacy and the level that they desired. Estimations of children’s average knowledge level varied widely and differed from the actual level. In particular, communicators overestimated the species literacy level. Although most biodiversity communicators agreed that knowledge about species is important, their view differed as to why species literacy would be important. Moreover, communicators differed with respect to the relative importance attached to different knowledge components. Professionals may thus benefit from a detailed framework of species literacy that illustrates different aspects and values. Most importantly, our findings suggest that to bridge the gap between actual and desired knowledge levels in children effectively, biodiversity communicators first need to become more aware of current perceptions in young audiences.
Semantic relation priming is not constituent-specific: Evidence from ERP
Authors: Jia Xiaofei , Zhou Changle
Published: November 2021

It is humankind’s unique wisdom to compose a limited number of words together through specific rules to convey endless information. Researchers have found that this composition process also plays a vital role in the comprehension of compounds. The specific manifestation is relation priming; that is, the previously used relation will promote subsequent word processing using the same relation. This priming phenomenon is bound to morpheme repetition (modifier or head). This study combines a self-paced priming paradigm with electrophysiological technology to explore whether relation priming will occur without sharing morphemes and its time course. We found that relation priming can occur independently of morpheme-repetition, which shows an independent representation of relation information. And it has been activated at a very early stage (about 200ms). As the word processing progresses, this activation gradually strengthens, indicating that the relation’s role is slowly increasing in the process of compound word recognition. It may first be used as a kind of context information to help determine the constituent morphemes’ meaning. After the meaning access of the constituent morphemes, they begin to play a role in the semantic composition process. This study uses electrophysiological technology to precisely describe the representation of relation and its time course for the first time. Which gives us a deeper understanding of the relation priming process, and at the same time, shed light on the meaning construction process of compounds.
Reduced platelet forces underlie impaired hemostasis in mouse models of MYH9-related disease
Authors: Baumann Juliane , Sachs Laura , Oliver Otto , Schoen Ingmar , Nestler Peter , Zaninetti Carlo , Kenny Martin , Kranz Ruth , von Eysmondt Hendrik , Rodriguez Johanna , Schäffer Tilman E. , Nagy Zoltan , Greinacher Andreas , Palankar Raghavendra , Bender Markus
Published: November 2021

MYH9-related disease patients with mutations in the contractile protein non-muscle myosin heavy chain IIA display, among others, macrothrombocytopenia and a mild to moderate bleeding tendency. In this study, we used three mouse lines, each with one point mutation in the Myh9 gene at positions 702, 1424, or 1841, to investigate mechanisms underlying the increased bleeding risk. Agonist-induced activation of Myh9 mutant platelets was comparable to controls. However, myosin light chain phosphorylation after activation was reduced in mutant platelets, which displayed altered biophysical characteristics and generated lower adhesion, interaction, and traction forces. Treatment with tranexamic acid restored clot retraction and reduced bleeding. We verified our findings from the mutant mice with platelets from patients with the respective mutation. These data suggest that reduced platelet forces lead to an increased bleeding tendency in MYH9-related disease patients, and treatment with tranexamic acid can improve the hemostatic function.

Teaser

Impaired hemostasis in Myh9 mutant mice due to reduced platelet forces can be improved by tranexamic acid.
SARS-CoV-2 ORF8 encoded protein contains a histone mimic, disrupts chromatin regulation, and enhances replication
Authors: Kee John , Thudium Samuel , Renner David , Glastad Karl , Palozola Katherine , Zhang Zhen , Li Yize , Cesare Joseph , Lan Yemin , Truitt Rachel , Cardenas-Diaz Fabian L. , Kotton Darrell N. , Alysandratos Konstantinos D. , Zhang Xianwen , Xie Xuping , Shi Pei-Yong , Yang Wenli , Morrisey Edward , Garcia Benjamin A. , Berger Shelley L. , Weiss Susan R. , Korb Erica
Published: November 2021

SARS-CoV-2 emerged in China at the end of 2019 and caused the global pandemic of COVID-19, a disease with high morbidity and mortality. While our understanding of this new virus is rapidly increasing, gaps remain in our understanding of how SARS-CoV-2 can effectively suppress host cell antiviral responses. Recent work on other viruses has demonstrated a novel mechanism through which viral proteins can mimic critical regions of human histone proteins. Histone proteins are responsible for governing genome accessibility and their precise regulation is critical for a cell’s ability to control transcription and respond to viral threats. Here, we show that the protein encoded by ORF8 (Orf8) in SARS-CoV-2 functions as a histone mimic of the ARKS motif in histone 3. Orf8 is associated with chromatin, binds to numerous histone-associated proteins, and is itself acetylated within the histone mimic site. Orf8 expression in cells disrupts multiple critical histone post-translational modifications (PTMs) including H3K9ac, H3K9me3, and H3K27me3 and promotes chromatin compaction while Orf8 lacking the histone mimic motif does not. Further, SARS-CoV-2 infection in human cell lines and postmortem patient lung tissue cause these same disruptions to chromatin. However, deletion of the Orf8 gene from SARS-CoV-2 largely blocks its ability to disrupt host-cell chromatin indicating that Orf8 is responsible for these effects. Finally, deletion of the ORF8 gene affects the host-cell transcriptional response to SARS-CoV-2 infection in multiple cell types and decreases the replication of SARS-CoV-2 in human induced pluripotent stem cell-derived lung alveolar type 2 (iAT2) pulmonary cells. These findings demonstrate a novel function for the poorly understood ORF8-encoded protein and a mechanism through which SARS-CoV-2 disrupts host cell epigenetic regulation. Finally, this work provides a molecular basis for the finding that SARS-CoV-2 lacking ORF8 is associated with decreased severity of COVID-19.
Measuring metabolic rate in single flies during sleep and waking states
Authors: Brown Elizabeth B. , Klok Jaco , Keene Alex C.
Published: November 2021

Drosophila melanogaster is a leading genetic model for studying the neural regulation of sleep. Sleep is associated with changes in behavior and physiological state that are largely conserved across species. The investigation of sleep in flies has predominantly focused on behavioral readouts of sleep because physiological measurements, including changes in brain activity and metabolic rate are less accessible. We have previously used stop-flow indirect calorimetry to measure whole body metabolic rate in single flies and have shown that in flies, like mammals, metabolic rate is reduced during sleep. Here, we describe a modified version of this system that allows for efficient and highly sensitive acquisition of CO2 output from single flies. We also describe a modification that allows for simultaneous acquisition of CO2 and O2 levels, providing a respiratory quotient that quantifies how metabolic stores are utilized. Finally, we show that sleep-dependent changes in metabolic rate are diminished in aging flies, supporting the notion that sleep quality is reduced as flies age. Taken together, the use of indirect calorimetry provides a physiological measure of sleep with broad applications to genetic studies in flies.
Rapid, Reliable and Robust approach for extraction-free RT-PCR based detection of SARS-CoV-2 in clinical setting to expedite large scale screening
Authors: Dubey Abhilasha , Upadhyay Sanjay , Mehta Manjeet
Published: November 2021

Rapid, reliable and robust method for the detection of SARS-CoV-2 is an indispensable need for diagnostics. The development of diagnostic method will aid to address further waves of the pandemic potentially with rapid surveillance of disease; and to allay the fears. To meet this challenge, we have developed a rapid RT-qPCR method for the detection of 3 target genes or confirmatory genes in less than 30 minutes. The assay showed 100% sensitivity and 100% specificity when tested on 120 samples. We compared a conventional extraction based method with extraction-free method, and then further reduced the run time of extraction free method. Additionally, we have validated our rapid RT-qPCR method for the assessment of pooled sample. We hereby propose a most reliable approach for the mass screening of samples with ease of operation at low cost. Finally we designed a single tube analysis method which provides qualitative as well as quantitative results in minimum time.
Mushroom Bodies Suppress Locomotor Activity in Drosophila melanogaster
Authors: Martin Jean-René , Ernst Roman , Heisenberg Martin
Published: November 2021

Locomotor activity of single, freely walking flies in small tubes is analyzed in the time domain of several hours. To assess the influence of the mushroom bodies on walking activity, three independent noninvasive methods interfering with mushroom body function are applied: chemical ablation of the mushroom body precursor cells; a mutant affecting Kenyon cell differentiation (mushroom body miniature1); and the targeted expression of the catalytic subunit of tetanus toxin in subsets of Kenyon cells. All groups of flies with mushroom body defects show an elevated level of total walking activity. This increase is attributable to the slower and less complete attenuation of activity during the experiment. Walking activity in normal and mushroom body-deficient flies is clustered in active phases (bouts) and rest periods (pauses). Neither the initiation nor the internal structure, but solely the termination of bouts seems to be affected by the mushroom body defects. How this finding relates to the well-documented role of the mushroom bodies in olfactory learning and memory remains to be understood.
Deficits in Memory Tasks of Mice with CREB Mutations Depend on Gene Dosage
Authors: Gass Peter , Wolfer David P. , Balschun Detlef , Rudolph Dorothea , Frey Uwe , Lipp Hans-Peter , Schütz Günther
Published: November 2021

Studies in Aplysia, Drosophila, and mice have shown that the transcription factor CREB is involved in formation and retention of long-term memory. To analyze the impact of differential CREB levels on learning and memory, we varied the gene dosage of CREB in two strains of mutant mice: (1) CREBαΔ mice, in which the α and Δ isoforms are disrupted, but a third isoform β is strongly up-regulated; (2) CREBcomp, a compound strain with one αΔ allele and one CREBnull allele in which all CREB isoforms are disrupted. To minimize genetic background effects, CREB mutations were backcrossed into a C57BL/6 and a FVB/N strain, respectively, and studies were performed in F1 hybrids from these lines. CREBcomp but not CREBαΔ F1 hybrids were impaired in water maze learning and fear conditioning, demonstrating a CREB gene dosage effect. However, analysis of the platform searching strategies in the water maze task suggested that CREBcomp mutants are impaired in behavioral flexibility rather than in spatial memory. In contrast to previous experiments using CREBαΔ mice with different genetic background, the F1 hybrid CREBαΔ and CREBcomp mice did not show deficits in a social transmission of food preference task nor in dentate gyrus and CA1 LTP as recorded from slice preparations. These data indicate that the hybrid vigor typical for F1 hybrids may compensate for a reduction in CREB levels in some tests. On the other hand, the persistence of clear behavioral deficits as shown by the F1hybrid CREBcomp mice in water maze and fear conditioning indicates a robust and repeatable phenomenon that will permit further functional analysis of CREB.
CA1 Long-Term Potentiation Is Diminished but Present in Hippocampal Slices from α-CaMKII Mutant Mice
Authors: Hinds Heather L. , Tonegawa Susumu , Malinow Roberto
Published: November 2021

Previous work has shown that mice missing the α-isoform of calcium–calmodulin-dependent protein kinase II (α-CaMKII) have a deficiency in CA1 hippocampal long-term potentiation (LTP). Follow-up studies on subsequent generations of these mutant mice in a novel inbred background by our laboratories have shown that whereas a deficiency in CA1 LTP is still present in α-CaMKII mutant mice, it is different both quantitatively and qualitatively from the deficiency first described. Mice of a mixed 129SvOla/SvJ;BALB/c;C57Bl/6 background derived from brother/sister mating of the α-CaMKII mutant line through multiple generations (>10) were produced by use of in vitro fertilization. Although LTP at 60 min post-tetanus was clearly deficient in these (−/−) α-CaMKII mice (42.6%, n = 33) compared with (+/+) α-CaMKII control animals (81.7%,n = 17), α-CaMKII mutant mice did show a significant level of LTP. The amount of LTP observed in α-CaMKII mutants was normally distributed, blocked by APV (2.7%, n = 8), and did not correlate with age. Although this supports a role for α-CaMKII in CA1 LTP, it also suggests that a form of α-CaMKII-independent LTP is present in mice that could be dependent on another kinase, such as the β-isoform of CaMKII. A significant difference in input/output curves was also observed between (−/−) α-CaMKII and (+/+) α-CaMKII animals, suggesting that differences in synaptic transmission may be contributing to the LTP deficit in mutant mice. However, tetani of increasing frequency (50, 100, and 200 Hz) did not reveal a higher threshold for potentiation in (−/−) α-CaMKII mice compared with (+/+) α-CaMKII controls.
Automated Measurement of Mouse Freezing Behavior and its Use for Quantitative Trait Locus Analysis of Contextual Fear Conditioning in (BALB/cJ × C57BL/6J)F2Mice
Authors: Valentinuzzi Verónica S. , Kolker Daniel E. , Vitaterna Martha Hotz , Shimomura Kazuhiro , Whiteley Andrew , Low-Zeddies Sharon , Turek Fred W. , Ferrari Elenice A.M. , Paylor Richard , Takahashi Joseph S.
Published: November 2021

The most commonly measured mouse behavior in fear conditioning tests is freezing. A technical limitation, particularly for genetic studies, is the method of direct observation used for quantifying this response, with the potential for bias or inconsistencies. We report the use of a computerized method based on latency between photobeam interruption measures as a reliable scoring criterion in mice. The different computer measures obtained during contextual fear conditioning tests showed high correlations with hand-scored freezing;rvalues ranged from 0.87 to 0.94. Previously reported strain differences between C57BL/6J and DBA/2J in context-dependent fear conditioning were also detected by the computer-based system. In addition, the use of computer-scored freezing of 199 (BALB/cJ × C57BL/6J)F2mice enabled us to detect a suggestive gender-dependent chromosomal locus for contextual fear conditioning on distal chromosome 8 by QTL analysis. Automation of freeze scoring would significantly increase efficiency and reliability of this learning and memory test.
A Specific Role for Group I mGluRs in Hippocampal LTP and Hippocampus-Dependent Spatial Learning
Authors: Balschun Detlef , Manahan-Vaughan Denise , Wagner Thomas , Behnisch Thomas , Reymann Klaus G. , Wetzel Wolfram
Published: November 2021

Metabotropic glutamate receptors (mGluRs) have been implicated in long-term potentiation and in learning and memory formation. In this study, we tested the effects of group I mGluR inhibition on synaptic plasticity and learning of rats at different levels of organization (1) in the hippocampal slice preparation; (2) in freely moving animals implanted with chronic hippocampal electrodes; and (3) in different spatial learning paradigms. To allow a direct comparison of the effects obtained the same doses were used in all paradigms. Bath-application of the selective group I mGluR antagonist (S)4-carboxyphenylglycine (4-CPG) impaired a decremental long-term potentiation (LTP) induced by a weak tetanization paradigm, but failed to affect a robust LTP generated by strong tetanization. In contrast, 4-CPG impaired a robust LTP in freely moving animals if applied 30 min before tetanization. The same dose of 4-CPG only impeded spatial learning mildly in the eight-arm radial maze and had no effect on a simple configuration of the Y-maze spatial alternation task. In the more difficult configuration of this task, however, 4-CPG caused complete amnesia. The lack of state-dependent 4-CPG actions and the absence of any 4-CPG effects in the open-field test classify the obtained retention deficit as a selective impairment of memory storage. Our results indicate a specific role of group I mGluRs in certain types of synaptic plasticity and of spatial learning.