bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide Association Study on Root Traits Under Different Growing Environments in Wheat (Triticum aestivum L.)
Authors: Xu Fengdan , Chen Shulin , Yang Xiwen , Zhou Sumei , Wang Junsen , Zhang Ziliang , Huang Yuan , Song Miao , Zhang Jun , Zhan Kehui , He Dexian
Published: June 2021

Plant roots are critical for water and nutrient acquisition, environmental adaptation, and yield formation. Herein, 196 wheat accessions from the Huang-Huai Wheat Region of China were collected to investigate six root traits at seedling stage under three growing environments [indoor hydroponic culture (IHC), outdoor hydroponic culture (OHC), and outdoor pot culture (OPC)] and the root dry weight (RDW) under OPC at four growth stages and four yield traits in four environments. Additionally, a genome-wide association study was performed with a Wheat 660K SNP Array. The results showed that the root traits varied most under OPC, followed by those under both OHC and IHC, and root elongation under hydroponic culture was faster than that under pot culture. Root traits under OHC might help predict those under OPC. Moreover, root traits were significantly negatively correlated with grain yield (GY) and grains per spike (GPS), positively correlated with thousand-kernel weight (TKW), and weakly correlated with number of spikes per area (SPA). Twelve stable chromosomal regions associated with the root traits were detected on chromosomes 1D, 2A, 4A, 4B, 5B, 6D, and unmapped markers. Among them, a stable chromosomal interval from 737.85 to 742.00 Mb on chromosome 4A, which regulated total root length (TRL), was identified under three growing environments. Linkage disequilibrium (LD) blocks were used to identify 27 genes related to root development. Three genes TraesCS4A02G484200, TraesCS4A02G484800, TraesCS4A02G493800, and TraesCS4A02G493900, are involved in cell elongation and differentiation and expressed at high levels in root tissues. Another vital co-localization interval on chromosome 5B (397.72–410.88 Mb) was associated with not only RDW under OHC and OPC but also TKW.
Omics in a Digital World: The Role of Bioinformatics in Providing New Insights Into Human Aging
Authors: Dato Serena , Crocco Paolina , Rambaldi Migliore Nicola , Lescai Francesco
Published: June 2021

Background

Aging is a complex phenotype influenced by a combination of genetic and environmental factors. Although many studies addressed its cellular and physiological age-related changes, the molecular causes of aging remain undetermined. Considering the biological complexity and heterogeneity of the aging process, it is now clear that full understanding of mechanisms underlying aging can only be achieved through the integration of different data types and sources, and with new computational methods capable to achieve such integration.

Recent Advances

In this review, we show that an omics vision of the age-dependent changes occurring as the individual ages can provide researchers with new opportunities to understand the mechanisms of aging. Combining results from single-cell analysis with systems biology tools would allow building interaction networks and investigate how these networks are perturbed during aging and disease. The development of high-throughput technologies such as next-generation sequencing, proteomics, metabolomics, able to investigate different biological markers and to monitor them simultaneously during the aging process with high accuracy and specificity, represents a unique opportunity offered to biogerontologists today.

Critical Issues

Although the capacity to produce big data drastically increased over the years, integration, interpretation and sharing of high-throughput data remain major challenges. In this paper we present a survey of the emerging omics approaches in aging research and provide a large collection of datasets and databases as a useful resource for the scientific community to identify causes of aging. We discuss their peculiarities, emphasizing the need for the development of methods focused on the integration of different data types.

Future Directions

We critically review the contribution of bioinformatics into the omics of aging research, and we propose a few recommendations to boost collaborations and produce new insights. We believe that significant advancements can be achieved by following major developments in bioinformatics, investing in diversity, data sharing and community-driven portable bioinformatics methods. We also argue in favor of more engagement and participation, and we highlight the benefits of new collaborations along these lines. This review aims at being a useful resource for many researchers in the field, and a call for new partnerships in aging research.
Non-Invasive Diagnosis for Acute Rejection Using Urinary mRNA Signature Reflecting Allograft Status in Kidney Transplantation
Authors: Seo Jung-Woo , Lee Yu Ho , Tae Dong Hyun , Park Seon Hwa , Moon Ju-Young , Jeong Kyung Hwan , Kim Chan-Duck , Chung Byung Ha , Park Jae Berm , Kim Yeong Hoon , Seok Junhee , Joo Sun Hyung , Lee Seung Hwan , Lee Jong Soo , Lee Sang-Ho
Published: June 2021

Urine has been regarded as a good resource based on the assumption that urine can directly reflect the state of the allograft or ongoing injury in kidney transplantation. Previous studies, suggesting the usefulness of urinary mRNA as a biomarker of acute rejection, imply that urinary mRNA mirrors the transcriptional activity of the kidneys. We selected 14 data-driven candidate genes through a meta-analysis and measured the candidate genes using quantitative PCR without pre-amplification in the cross-sectional specimens from Korean kidney transplant patients. Expression of 9/14 genes (CXCL9, CD3ϵ, IP-10, LCK, C1QB, PSMB9, Tim-3, Foxp3, and FAM26F) was significantly different between acute rejection and stable graft function with normal pathology and long-term graft survival in 103 training samples. CXCL9 was also distinctly expressed in allografts with acute rejection in in situ hybridization analysis. This result, consistent with the qPCR result, implies that urinary mRNA could reflect the magnitude of allograft injury. We developed an AR prediction model with the urinary mRNAs by a binary logistic regression and the AUC of the model was 0.89 in the training set. The model was validated in 391 independent samples, and the AUC value yielded 0.84 with a fixed manner. In addition, the decision curve analysis indicated a range of reasonable threshold probabilities for biopsy. Therefore, we suggest the urine mRNA signature could be used as a non-invasive monitoring tool of acute rejection for clinical application and could help determine whether to perform a biopsy in a recipient with increased creatinine.
Treg: A Promising Immunotherapeutic Target in Oral Diseases
Authors: Zhang Yujing , Guo Jihua , Jia Rong
Published: June 2021

With the pandemic of COVID-19, maintenance of oral health has increasingly become the main challenge of global health. Various common oral diseases, such as periodontitis and oral cancer, are closely associated with immune disorders in the oral mucosa. Regulatory T cells (Treg) are essential for maintaining self-tolerance and immunosuppression. During the process of periodontitis and apical periodontitis, two typical chronic immune-inflammatory diseases, Treg contributes to maintain host immune homeostasis and minimize tissue damage. In contrast, in the development of oral precancerous lesions and oral cancer, Treg is expected to be depleted or down-regulated to enhance the anti-tumor immune response. Therefore, a deeper understanding of the distribution, function, and regulatory mechanisms of Treg cells may provide a prospect for the immunotherapy of oral diseases. In this review, we summarize the distribution and multiple roles of Treg in different oral diseases and discuss the possible mechanisms involved in Treg cell regulation, hope to provide a reference for future Treg-targeted immunotherapy in the treatment of oral diseases.
Functional Contribution and Targeted Migration of Group-2 Innate Lymphoid Cells in Inflammatory Lung Diseases: Being at the Right Place at the Right Time
Authors: Wirtz Stefan , Schulz-Kuhnt Anja , Neurath Markus F. , Atreya Imke
Published: June 2021

During the last decade, group-2 innate lymphoid cells (ILC2s) have been discovered and successfully established as crucial mediators of lung allergy, airway inflammation and fibrosis, thus affecting the pathogenesis and clinical course of many respiratory diseases, like for instance asthma, cystic fibrosis and chronic rhinosinusitis. As an important regulatory component in this context, the local pulmonary milieu at inflammatory tissue sites does not only determine the activation status of lung-infiltrating ILC2s, but also influences their motility and migratory behavior. In general, many data collected in recent murine and human studies argued against the former concept of a very strict tissue residency of innate lymphoid cells (ILCs) and instead pointed to a context-dependent homing capacity of peripheral blood ILC precursors and the inflammation-dependent capacity of specific ILC subsets for interorgan trafficking. In this review article, we provide a comprehensive overview of the so far described molecular mechanisms underlying the pulmonary migration of ILC2s and thereby the numeric regulation of local ILC2 pools at inflamed or fibrotic pulmonary tissue sites and discuss their potential to serve as innovative therapeutic targets in the treatment of inflammatory lung diseases.
Regulation of Free Fatty Acid Receptor 4 on Inflammatory Gene Induced by LPS in Large Yellow Croaker (Larimichthys crocea)
Authors: Wu Mengjiao , Li Qingfei , Mai Kangsen , Ai Qinghui
Published: June 2021

Free fatty acid receptor 4 (FFAR4) plays a key role in regulating the inflammatory response in mammals. The present study aimed to investigate the function of large yellow croaker FFAR4 on inflammation. In the present study,ffar4was widely expressed in 10 tissues of large yellow croaker including gill, head kidney and spleen. Further studies showed that treatment of head kidney macrophages with agonists (TUG891 or GSK137647A) or overexpression offfar4reduced the mRNA expression of pro-inflammatory genes induced by LPS, and increased the expression ofpparγ. Treatment of macrophages with antagonist AH7614 increased the mRNA expression of pro-inflammatory genes induced by LPS, and decreased the mRNA expression ofpparγ. In order to verify the immunomodulatory effect of PPARγ, PPARγ was overexpressed in macrophages which significantly reduced the mRNA expression of pro-inflammatory genesil6,il1β,il8,tnfαandcox2. Moreover, results of dual-luciferase assays showed that PPARγ downregulated the transcriptional activity ofil6andil1βpromoters. In conclusion, FFAR4 showed anti-inflammatory effects on LPS-induced inflammation in large yellow croaker.
Comparing the Performance of a Remotely Operated Vehicle, a Drop Camera, and a Trawl in Capturing Deep-Sea Epifaunal Abundance and Diversity
Authors: de Mendonça Sarah N. , Metaxas Anna
Published: June 2021

Deep-sea ecosystems provide services such as food, minerals, and nutrient recycling, yet baseline data on their structure is often lacking. Our limited knowledge of vulnerable deep-sea ecosystems presents a challenge for effective monitoring and mitigation of increasing anthropogenic threats, including destructive fishing and climate change. Using data from two stations differing in total epifaunal abundance and taxonomic composition, we compared the use of imagery collected by two non-invasive tools [remotely operated vehicle (ROV) and drop camera] and data collected with a trawl system, commonly used to quantify epibenthic megafauna in the deep sea. Imagery and trawl data captured different epifaunal patterns, the former being more efficient for capturing epifauna, particularly Pennatulacean recruits. The image-based methods also caused less disturbance, had higher position accuracy, and allow for analyses of spatial structure and species associations; fine-scale distributions could not be elucidated with a trawl. Abundance was greater for some taxa, and diversity accumulated faster with increasing sample size for the drop camera than the ROV at one station. However, there are trade-offs between these tools, including continuous and discrete sampling for the ROV and drop camera, respectively, which can affect follow-up analyses. Our results can be used to inform monitoring frameworks on the use of appropriate sampling tools. We recommend further research into tool sampling biases and biometric relationships to help integrate datasets collected with different tools.
Toward a Country-Based Prediction Model of COVID-19 Infections and Deaths Between Disease Apex and End: Evidence From Countries With Contained Numbers of COVID-19
Authors: Gu Tianshu , Wang Lishi , Xie Ning , Meng Xia , Li Zhijun , Postlethwaite Arnold , Aleya Lotfi , Howard Scott C. , Gu Weikuan , Wang Yongjun
Published: June 2021

The complexity of COVID-19 and variations in control measures and containment efforts in different countries have caused difficulties in the prediction and modeling of the COVID-19 pandemic. We attempted to predict the scale of the latter half of the pandemic based on real data using the ratio between the early and latter halves from countries where the pandemic is largely over. We collected daily pandemic data from China, South Korea, and Switzerland and subtracted the ratio of pandemic days before and after the disease apex day of COVID-19. We obtained the ratio of pandemic data and created multiple regression models for the relationship between before and after the apex day. We then tested our models using data from the first wave of the disease from 14 countries in Europe and the US. We then tested the models using data from these countries from the entire pandemic up to March 30, 2021. Results indicate that the actual number of cases from these countries during the first wave mostly fall in the predicted ranges of liniar regression, excepting Spain and Russia. Similarly, the actual deaths in these countries mostly fall into the range of predicted data. Using the accumulated data up to the day of apex and total accumulated data up to March 30, 2021, the data of case numbers in these countries are falling into the range of predicted data, except for data from Brazil. The actual number of deaths in all the countries are at or below the predicted data. In conclusion, a linear regression model built with real data from countries or regions from early pandemics can predict pandemic scales of the countries where the pandemics occur late. Such a prediction with a high degree of accuracy provides valuable information for governments and the public.
Acute Urticaria in Inpatients Undergoing Non-emergent Coronary Angiography With Corticosteroid Prophylaxis: A Retrospective Study
Authors: Chen Bangtao , Yu Fubing , Chen WenChieh , Wang Yong , Hao Fei
Published: June 2021

Background and Aims: Acute urticaria (AU) is the most frequently reported immediate hypersensitivity reaction in skin by administration of iodinated contrast media (ICM). We aimed to establish the pattern and identify the risk factors of AU among inpatients undergoing non-emergent coronary angiography (CAG) with prophylactic corticosteroids in China.

Methods: Medical records of 19,326 adult inpatients undergoing non-emergent CAG with prophylactic methylprednisolone in 2013–2019 were retrospectively investigated. AU was identified within 1 h post-ICM administration, and diffuse involvement was defined when wheals occur in two or more body parts, including the back, abdomen, chest, and extremities. Age- and sex-matched inpatients (1:4) without AU were randomly selected for assessment of risk factors.

Results: Approximately 0.8% of CAG inpatients had AU, including 101 diffuse and 64 limited form. The diffuse AU was more common in settings of non-diagnostic CAG, iohexol used, average ICM injection≥3 ml/min, recurrent CAG, and past history of immediate hypersensitivity to ICM. Inpatients with preexisting allergies, decreased evaluated glomerular filtration rate, and increased high sensitivity C reactive protein or neutrophil-to-lymphocyte ratio prior to CAG had a higher probability of AU (odds ratio >1, P < 0.05 for all variables). All AU inpatients complained of pruritus, and mild itching predominated. AU dissipated in several days under treatment of ebastine or levocetirizine 10 mg/daily, but ebastine showed superiority.

Conclusions: ICM-induced AU is not uncommon in non-emergent CAG inpatients with prophylactic methylprednisolone. Preexisting allergies, renal dysfunction, and mild inflammation are high-risk factors, and antihistamine monotherapy is a favorable candidate for ICM-related AU.
Molecular and Mechanistic Characterization of PddB, the First PLP-Independent 2,4-Diaminobutyric Acid Racemase Discovered in an Actinobacterial D-Amino Acid Homopolymer Biosynthesis
Authors: Yamanaka Kazuya , Ozaki Ryo , Hamano Yoshimitsu , Oikawa Tadao
Published: June 2021

We recently disclosed that the biosynthesis of antiviral γ-poly-D-2,4-diaminobutyric acid (poly-D-Dab) in Streptoalloteichus hindustanus involves an unprecedented cofactor independent stereoinversion of Dab catalyzed by PddB, which shows weak homology to diaminopimelate epimerase (DapF). Enzymological properties and mechanistic details of this enzyme, however, had remained to be elucidated. Here, through a series of biochemical characterizations, structural modeling, and site-directed mutageneses, we fully illustrate the first Dab-specific PLP-independent racemase PddB and further provide an insight into its evolution. The activity of the recombinant PddB was shown to be optimal around pH 8.5, and its other fundamental properties resembled those of typical PLP-independent racemases/epimerases. The enzyme catalyzed Dab specific stereoinversion with a calculated equilibrium constant of nearly unity, demonstrating that the reaction catalyzed by PddB is indeed racemization. Its activity was inhibited upon incubation with sulfhydryl reagents, and the site-directed substitution of two putative catalytic Cys residues led to the abolishment of the activity. These observations provided critical evidence that PddB employs the thiolate-thiol pair to catalyze interconversion of Dab isomers. Despite the low levels of sequence similarity, a phylogenetic analysis of PddB indicated its particular relevance to DapF among PLP-independent racemases/epimerases. Secondary structure prediction and 3D structural modeling of PddB revealed its remarkable conformational analogy to DapF, which in turn allowed us to predict amino acid residues potentially responsible for the discrimination of structural difference between diaminopimelate and its specific substrate, Dab. Further, PddB homologs which seemed to be narrowly distributed only in actinobacterial kingdom were constantly encoded adjacent to the putative poly-D-Dab synthetase gene. These observations strongly suggested that PddB could have evolved from the primary metabolic DapF in order to organize the biosynthesis pathway for the particular secondary metabolite, poly-D-Dab. The present study is on the first molecular characterization of PLP-independent Dab racemase and provides insights that could contribute to further discovery of unprecedented PLP-independent racemases.
Molecular Epidemiology, Evolution and Reemergence of Chikungunya Virus in South Asia
Authors: Sharif Nadim , Sarkar Mithun Kumar , Ferdous Rabeya Nahar , Ahmed Shamsun Nahar , Billah Md. Baki , Talukder Ali Azam , Zhang Ming , Dey Shuvra Kanti
Published: June 2021

Chikungunya virus (CHIKV) is a vector (mosquito)-transmitted alphavirus (family Togaviridae). CHIKV can cause fever and febrile illness associated with severe arthralgia and rash. Genotypic and phylogenetic analysis are important to understand the spread of CHIKV during epidemics and the diversity of circulating strains for the prediction of effective control measures. Molecular epidemiologic analysis of CHIKV is necessary to understand the complex interaction of vectors, hosts and environment that influences the genotypic evolution of epidemic strains. In this study, different works published during 1950s to 2020 concerning CHIKV evolution, epidemiology, vectors, phylogeny, and clinical outcomes were analyzed. Outbreaks of CHIKV have been reported from Bangladesh, Bhutan, India, Pakistan, Sri Lanka, Nepal, and Maldives in South Asia during 2007–2020. Three lineages- Asian, East/Central/South African (ECSA), and Indian Ocean Lineage (IOL) are circulating in South Asia. Lineage, ECSA and IOL became predominant over Asian lineage in South Asian countries during 2011–2020 epidemics. Further, the mutant E1-A226V is circulating in abundance with Aedes albopictus in India, Bangladesh, Nepal, and Bhutan. CHIKV is underestimated as clinical symptoms of CHIKV infection merges with the symptoms of dengue fever in South Asia. Failure to inhibit vector mediated transmission and predict epidemics of CHIKV increase the risk of larger global epidemics in future. To understand geographical spread of CHIKV, most of the studies focused on CHIKV outbreak, biology, pathogenesis, infection, transmission, and treatment. This updated study will reveal the collective epidemiology, evolution and phylogenies of CHIKV, supporting the necessity to investigate the circulating strains and vectors in South Asia.
Interactions Between Aging and Alzheimer’s Disease on Structural Brain Networks
Authors: Wu Zhanxiong , Gao Yunyuan , Potter Thomas , Benoit Julia , Shen Jian , Schulz Paul E. , Zhang Yingchun ,   and The Alzheimer’s Disease Neuroimaging Initiative
Published: June 2021

Normative aging and Alzheimer’s disease (AD) propagation alter anatomical connections among brain parcels. However, the interaction between the trajectories of age- and AD-linked alterations in the topology of the structural brain network is not well understood. In this study, diffusion-weighted magnetic resonance imaging (MRI) datasets of 139 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were used to document their structural brain networks. The 139 participants consist of 45 normal controls (NCs), 37 with early mild cognitive impairment (EMCI), 27 with late mild cognitive impairment (LMCI), and 30 AD patients. All subjects were further divided into three subgroups based on their age (56–65, 66–75, and 71–85 years). After the structural connectivity networks were built using anatomically-constrained deterministic tractography, their global and nodal topological properties were estimated, including network efficiency, characteristic path length, transitivity, modularity coefficient, clustering coefficient, and betweenness. Statistical analyses were then performed on these metrics using linear regression, and one- and two-way ANOVA testing to examine group differences and interactions between aging and AD propagation. No significant interactions were found between aging and AD propagation in the global topological metrics (network efficiency, characteristic path length, transitivity, and modularity coefficient). However, nodal metrics (clustering coefficient and betweenness centrality) of some cortical parcels exhibited significant interactions between aging and AD propagation, with affected parcels including left superior temporal, right pars triangularis, and right precentral. The results collectively confirm the age-related deterioration of structural networks in MCI and AD patients, providing novel insight into the cross effects of aging and AD disorder on brain structural networks. Some early symptoms of AD may also be due to age-associated anatomic vulnerability interacting with early anatomic changes associated with AD.
The Role of Brief Global Cognitive Tests and Neuropsychological Expertise in the Detection and Differential Diagnosis of Dementia
Authors: Riello Marianna , Rusconi Elena , Treccani Barbara
Published: June 2021

Dementia is a global public health problem and its impact is bound to increase in the next decades, with a rapidly aging world population. Dementia is by no means an obligatory outcome of aging, although its incidence increases exponentially in old age, and its onset may be insidious. In the absence of unequivocal biomarkers, the accuracy of cognitive profiling plays a fundamental role in the diagnosis of this condition. In this Perspective article, we highlight the utility of brief global cognitive tests in the diagnostic process, from the initial detection stage for which they are designed, through the differential diagnosis of dementia. We also argue that neuropsychological training and expertise are critical in order for the information gathered from these omnibus cognitive tests to be used in an efficient and effective way, and thus, ultimately, for them to fulfill their potential.
Voxel-Based Morphometry of Cerebellar Lobules in Essential Tremor
Authors: Ågren Richard , Awad Amar , Blomstedt Patric , Fytagoridis Anders
Published: June 2021

Background

The extent of neurodegeneration underlying essential tremor (ET) remains a matter of debate. Despite various extents of cerebellar atrophy on structural magnetic resonance imaging (MRI), previous studies have shown substantial heterogeneity and included a limited number of patients. Novel automated pipelines allow detailed segmentation of cerebellar lobules based on structural MRI.

Objective

To compare the volumes of cerebellar lobules in ET patients with those in healthy controls (HCs) using an automated segmentation pipeline.

Methods

Structural MRI scans of ET patients eligible for deep brain stimulation (n = 55) and of age-matched and gender-matched HCs (n = 55, from the IXI database) were segmented using the automated CEREbellum Segmentation pipeline. Lobule-specific volume differences between the ET and HC groups were evaluated using a general linear model corrected for multiple tests.

Results

Total brain tissue volumes did not differ between the ET and HC groups. ET patients demonstrated reduced volumes of lobules I-II, left Crus II, left VIIB, and an increased volume of right X when compared with the HC group.

Conclusion

A large cohort of ET patients demonstrated subtle signs of decreased cerebellar lobule volumes. These findings oppose the hypothesis of localized atrophy in cerebellar motor areas in ET, but not the possibility of cerebellar pathophysiology in ET. Prospective investigations using alternative neuroimaging modalities may further elucidate the pathophysiology of ET and provide insights into diagnostic and therapeutic approaches.
A Guide for Using Flight Simulators to Study the Sensory Basis of Long-Distance Migration in Insects
Authors: Dreyer David , Frost Barrie , Mouritsen Henrik , Lefèvre Adrien , Menz Myles , Warrant Eric
Published: June 2021

Studying the routes flown by long-distance migratory insects comes with the obvious challenge that the animal’s body size and weight is comparably low. This makes it difficult to attach relatively heavy transmitters to these insects in order to monitor their migratory routes (as has been done for instance in several species of migratory birds. However, the rather delicate anatomy of insects can be advantageous for testing their capacity to orient with respect to putative compass cues during indoor experiments under controlled conditions. Almost 20 years ago, Barrie Frost and Henrik Mouritsen developed a flight simulator which enabled them to monitor the heading directions of tethered migratory Monarch butterflies, both indoors and outdoors. The design described in the original paper has been used in many follow-up studies to describe the orientation capacities of mainly diurnal lepidopteran species. Here we present a modification of this flight simulator design that enables studies of nocturnal long-distance migration in moths while allowing controlled magnetic, visual and mechanosensory stimulation. This modified flight simulator has so far been successfully used to study the sensory basis of migration in two European and one Australian migratory noctuid species.
Auxiliary Subunits Control Function and Subcellular Distribution of AMPA Receptor Complexes in NG2 Glia of the Developing Hippocampus
Authors: Hardt Stefan , Tascio Dario , Passlick Stefan , Timmermann Aline , Jabs Ronald , Steinhäuser Christian , Seifert Gerald
Published: June 2021

Synaptic and axonal glutamatergic signaling to NG2 glia in white matter is critical for the cells’ differentiation and activity dependent myelination. However, in gray matter the impact of neuron-to-NG2 glia signaling is still elusive, because most of these cells keep their non-myelinating phenotype throughout live. Early in postnatal development, hippocampal NG2 glia express AMPA receptors with a significant Ca2+ permeability allowing for plasticity of the neuron-glia synapses, but whether this property changes by adulthood is not known. Moreover, it is unclear whether NG2 glia express auxiliary transmembrane AMPA receptor related proteins (TARPs), which modify AMPA receptor properties, including their Ca2+ permeability. Through combined molecular and functional analyses, here we show that hippocampal NG2 glia abundantly express TARPs γ4, γ7, and γ8 as well as cornichon (CNIH)-2. TARP γ8 undergoes profound downregulation during development. Receptors of adult NG2 glia showed an increased sensitivity to blockers of Ca2+ permeable AMPA receptors, but this increase mainly concerned receptors located close to the soma. Evoked synaptic currents of NG2 glia were also sensitive to blockers of Ca2+ permeable AMPA receptors. The presence of AMPA receptors with varying Ca2+ permeability during postnatal maturation may be important for the cells’ ability to sense and respond to local glutamatergic activity and for regulating process motility, differentiation, and proliferation.
Neuronal Graphs: A Graph Theory Primer for Microscopic, Functional Networks of Neurons Recorded by Calcium Imaging
Authors: Nelson Carl J. , Bonner Stephen
Published: June 2021

Connected networks are a fundamental structure of neurobiology. Understanding these networks will help us elucidate the neural mechanisms of computation. Mathematically speaking these networks are “graphs”—structures containing objects that are connected. In neuroscience, the objects could be regions of the brain, e.g., fMRI data, or be individual neurons, e.g., calcium imaging with fluorescence microscopy. The formal study of graphs, graph theory, can provide neuroscientists with a large bank of algorithms for exploring networks. Graph theory has already been applied in a variety of ways to fMRI data but, more recently, has begun to be applied at the scales of neurons, e.g., from functional calcium imaging. In this primer we explain the basics of graph theory and relate them to features of microscopic functional networks of neurons from calcium imaging—neuronal graphs. We explore recent examples of graph theory applied to calcium imaging and we highlight some areas where researchers new to the field could go awry.
Interneuron Types and Their Circuits in the Basolateral Amygdala
Authors: Hájos Norbert
Published: June 2021

The basolateral amygdala (BLA) is a cortical structure based on its cell types, connectivity features, and developmental characteristics. This part of the amygdala is considered to be the main entry site of processed and multisensory information delivered via cortical and thalamic afferents. Although GABAergic inhibitory cells in the BLA comprise only 20% of the entire neuronal population, they provide essential control over proper network operation. Previous studies have uncovered that GABAergic cells in the basolateral amygdala are as diverse as those present in other cortical regions, including the hippocampus and neocortex. To understand the role of inhibitory cells in various amygdala functions, we need to reveal the connectivity and input-output features of the different types of GABAergic cells. Here, I review the recent achievements in uncovering the diversity of GABAergic cells in the basolateral amygdala with a specific focus on the microcircuit organization of these inhibitory cells.
Analysis of Prognostic Risk Factors Determining Poor Functional Recovery After Comprehensive Rehabilitation Including Motor-Imagery Brain-Computer Interface Training in Stroke Patients: A Prospective Study
Authors: Wu Qiong , Ge Yunxiang , Ma Di , Pang Xue , Cao Yingyu , Zhang Xiaofei , Pan Yu , Zhang Tong , Dou Weibei
Published: June 2021

Objective: Upper limb (UL) motor function recovery, especially distal function, is one of the main goals of stroke rehabilitation as this function is important to perform activities of daily living (ADL). The efficacy of the motor-imagery brain-computer interface (MI-BCI) has been demonstrated in patients with stroke. Most patients with stroke receive comprehensive rehabilitation, including MI-BCI and routine training. However, most aspects of MI-BCI training for patients with subacute stroke are based on routine training. Risk factors for inadequate distal UL functional recovery in these patients remain unclear; therefore, it is more realistic to explore the prognostic factors of this comprehensive treatment based on clinical practice. The present study aims to investigate the independent risk factors that might lead to inadequate distal UL functional recovery in patients with stroke after comprehensive rehabilitation including MI-BCI (CRIMI-BCI).

Methods: This prospective study recruited 82 patients with stroke who underwent CRIMI-BCI. Motor-imagery brain-computer interface training was performed for 60 min per day, 5 days per week for 4 weeks. The primary outcome was improvement of the wrist and hand dimensionality of Fugl-Meyer Assessment (δFMA-WH). According to the improvement score, the patients were classified into the efficient group (EG, δFMA-WH > 2) and the inefficient group (IG, δFMA-WH ≤ 2). Binary logistic regression was used to analyze clinical and demographic data, including aphasia, spasticity of the affected hand [assessed by Modified Ashworth Scale (MAS-H)], initial UL function, age, gender, time since stroke (TSS), lesion hemisphere, and lesion location.

Results: Seventy-three patients completed the study. After training, all patients showed significant improvement in FMA-UL (Z = 7.381, p = 0.000**), FMA-SE (Z = 7.336, p = 0.000**), and FMA-WH (Z = 6.568, p = 0.000**). There were 35 patients (47.9%) in the IG group and 38 patients (52.1%) in the EG group. Multivariate analysis revealed that presence of aphasia [odds ratio (OR) 4.617, 95% confidence interval (CI) 1.435–14.860; p < 0.05], initial FMA-UL score ≤ 30 (OR 5.158, 95% CI 1.150–23.132; p < 0.05), and MAS-H ≥ level I+ (OR 3.810, 95% CI 1.231–11.790; p < 0.05) were the risk factors for inadequate distal UL functional recovery in patients with stroke after CRIMI-BCI.

Conclusion: We concluded that CRIMI-BCI improved UL function in stroke patients with varying effectiveness. Inferior initial UL function, significant hand spasticity, and presence of aphasia were identified as independent risk factors for inadequate distal UL functional recovery in stroke patients after CRIMI-BCI.
Safety and Efficacy of Low-Dose Tirofiban Combined With Intravenous Thrombolysis and Mechanical Thrombectomy in Acute Ischemic Stroke: A Matched-Control Analysis From a Nationwide Registry
Authors: Ma Gaoting , Li Shuo , Jia Baixue , Mo Dapeng , Ma Ning , Gao Feng , Huo Xiaochuan , Luo Gang , Wang Anxin , Pan Yuesong , Song Ligang , Sun Xuan , Zhang Xuelei , Gui Liqiang , Song Cunfeng , Peng Ya , Wu Jin , Zhao Shijun , Zhao Junfeng , Zhou Zhiming , Miao Zhongrong
Published: June 2021

Purpose: Tirofiban administration to acute ischemic stroke patients undergoing mechanical thrombectomy with preceding intravenous thrombolysis remains controversial. The aim of the current study was to evaluate the safety and efficacy of low-dose tirofiban during mechanical thrombectomy in patients with preceding intravenous thrombolysis.

Methods: Patients with acute ischemic stroke undergoing mechanical thrombectomy and preceding intravenous thrombolysis were derived from “ANGEL-ACT,” a multicenter, prospective registry study. The patients were dichotomized into tirofiban and non-tirofiban groups based on whether tirofiban was administered. Propensity score matching was used to minimize case bias. The primary safety endpoint was symptomatic intracerebral hemorrhage (sICH), defined as an intracerebral hemorrhage (ICH) associated with clinical deterioration as determined by the Heidelberg Bleeding Classification. All ICHs and hemorrhage types were recorded. Clinical outcomes included successful recanalization, dramatic clinical improvement, functional independence, and mortality at the 3-month follow-up timepoint. Successful recanalization was defined as a modified Thrombolysis in Cerebral Ischemia score of 2b or 3. Dramatic clinical improvement at 24 h was defined as a reduction in NIH stroke score of ≥10 points compared with admission, or a score ≤1. Functional independence was defined as a Modified Rankin Scale (mRS) score of 0–2 at 3-months.

Results: The study included 201 patients, 81 in the tirofiban group and 120 in the non-tirofiban group, and each group included 68 patients after propensity score matching. Of the 201 patients, 52 (25.9%) suffered ICH, 15 (7.5%) suffered sICH, and 18 (9.0%) died within 3-months. The median mRS was 3 (0–4), 99 (49.3%) achieved functional independence. There were no statistically significant differences in safety outcomes, efficacy outcomes on successful recanalization, dramatic clinical improvement, or 3-month mRS between the tirofiban and non-tirofiban groups (all p > 0.05). Similar results were obtained after propensity score matching.

Conclusion: In acute ischemic stroke patients who underwent mechanical thrombectomy and preceding intravenous thrombolysis, low-dose tirofiban was not associated with increased risk of sICH or ICH. Further randomized clinical trials are needed to confirm the effects of tirofiban in patients undergoing bridging therapy.
Disrupted Structural Brain Connectome Is Related to Cognitive Impairment in Patients With Ischemic Leukoaraiosis
Authors: Lu Tong , Wang Zan , Cui Ying , Zhou Jiaying , Wang Yuancheng , Ju Shenghong
Published: June 2021

Ischemic leukoaraiosis (ILA) is related to cognitive impairment and vascular dementia in the elderly. One possible mechanism could be the disruption of white matter (WM) tracts and network function that connect distributed brain regions involved in cognition. The purpose of this study was to investigate the relationship between structural connectome and cognitive functions in ILA patients. A total of 89 patients with ILA (Fazekas score ≥ 3) and 90 healthy controls (HCs) underwent comprehensive neuropsychological examinations and diffusion tensor imaging scans. The tract-based spatial statistics approach was employed to investigate the WM integrity. Graph theoretical analysis was further applied to construct the topological architecture of the structural connectome in ILA patients. Partial correlation analysis was used to investigate the relationships between network measures and cognitive performances in the ILA group. Compared with HCs, the ILA patients showed widespread WM integrity disruptions. The ILA group displayed increased characteristic path length (Lp) and decreased global network efficiency at the level of the whole brain relative to HCs, and reduced nodal efficiencies, predominantly in the frontal–subcortical and limbic system regions. Furthermore, these structural connectomic alterations were associated with cognitive impairment in ILA patients. The association between WM changes (i.e., fractional anisotropy and mean diffusivity measures) and cognitive function was mediated by the structural connectivity measures (i.e., local network efficiency and Lp). In conclusion, cognitive impairment in ILA patients is related to microstructural disruption of multiple WM fibers and topological disorganization of structural networks, which have implications in understanding the relationship between ILA and the possible attendant cognitive impairment.
Application of High-Frequency Oscillations on Scalp EEG in Infant Spasm: A Prospective Controlled Study
Authors: Yan Lisi , Li Lin , Chen Jin , Wang Li , Jiang Li , Hu Yue
Published: June 2021

Objective

We quantitatively analyzed high-frequency oscillations (HFOs) using scalp electroencephalography (EEG) in patients with infantile spasms (IS).

Methods

We enrolled 60 children with IS hospitalized from January 2019 to August 2020. Sixty healthy age-matched children comprised the control group. Time–frequency analysis was used to quantify γ, ripple, and fast ripple (FR) oscillation energy changes.

Results

γ, ripple, and FR oscillations dominated in the temporal and frontal lobes. The average HFO energy of the sleep stage is lower than that of the wake stage in the same frequency bands in both the normal control (NC) and IS groups (P < 0.05). The average HFO energy of the IS group was significantly higher than that of the NC group in γ band during sleep stage (P < 0.01). The average HFO energy of S and Post-S stage were higher than that of sleep stage in γ band (P < 0.05). In the ripple band, the average HFO energy of Pre-S, S, and Post-S stage was higher than that of sleep stage (P < 0.05). Before treatment, there was no significant difference in BASED score between the effective and ineffective groups. The interaction of curative efficacy × frequency and the interaction of curative efficacy × state are statistically significant. The average HFO energy of the effective group was lower than that of the ineffective group in the sleep stage (P < 0.05). For the 16 children deemed “effective” in the IS group, the average HFO energy of three frequency bands was not significantly different before compared with after treatment.

Significance

Scalp EEG can record HFOs. The energy of HFOs can distinguish physiological HFOs from pathological ones more accurately than frequency. On scalp EEG, γ oscillations can better detect susceptibility to epilepsy than ripple and FR oscillations. HFOs can trigger spasms. The analysis of average HFO energy can be used as a predictor of the effectiveness of epilepsy treatment.
Event-Based Update of Synapses in Voltage-Based Learning Rules
Authors: Stapmanns Jonas , Hahne Jan , Helias Moritz , Bolten Matthias , Diesmann Markus , Dahmen David
Published: June 2021

Due to the point-like nature of neuronal spiking, efficient neural network simulators often employ event-based simulation schemes for synapses. Yet many types of synaptic plasticity rely on the membrane potential of the postsynaptic cell as a third factor in addition to pre- and postsynaptic spike times. In some learning rules membrane potentials not only influence synaptic weight changes at the time points of spike events but in a continuous manner. In these cases, synapses therefore require information on the full time course of membrane potentials to update their strength which a priori suggests a continuous update in a time-driven manner. The latter hinders scaling of simulations to realistic cortical network sizes and relevant time scales for learning. Here, we derive two efficient algorithms for archiving postsynaptic membrane potentials, both compatible with modern simulation engines based on event-based synapse updates. We theoretically contrast the two algorithms with a time-driven synapse update scheme to analyze advantages in terms of memory and computations. We further present a reference implementation in the spiking neural network simulator NEST for two prototypical voltage-based plasticity rules: the Clopath rule and the Urbanczik-Senn rule. For both rules, the two event-based algorithms significantly outperform the time-driven scheme. Depending on the amount of data to be stored for plasticity, which heavily differs between the rules, a strong performance increase can be achieved by compressing or sampling of information on membrane potentials. Our results on computational efficiency related to archiving of information provide guidelines for the design of learning rules in order to make them practically usable in large-scale networks.
Large-Area Photoreceptor Degeneration Model in Rabbits by Photocoagulation and Oxidative Stress in the Retina
Authors: Wang Zhexuan , Feng Chenli , Yang Ruyi , Liu Tingting , Chen Yin , Chen Aihua , Yan Biao , Yuan Yuanzhi , Zhang Jiayi
Published: June 2021

Photocoagulation is used for the treatment of retinal ischemic disease. However, due to the invasive nature of photocoagulation and variety of melanin concentrations between individuals, it is challenging to avoid damaging the adjacent photoreceptors and inducing several side effects. Previous studies indicate the role of laser power, duration, and spot size on retinal lesions, but the effect of interspot distance of the laser pulses needs to be considered in panretinal photocoagulation. In this study, we examine different parameters of photocoagulation on lesions of the retina in rabbit, finding that the lesion level of the outer nuclear layer of the retina depended on the pulse duration and laser spot size, and decreasing interspot distance could completely abolish the photoreceptor layer. The degeneration of the photoreceptor by photocoagulation occurred in 24 h and was not restored afterward. We then conducted panretinal photocoagulation in rabbit and found that oxidative stress was decreased in the inner nuclear layer of the retina, and pupillary light reflex and ERG signals were impaired. Our study could provide a rabbit model to explore the mechanism of photoreceptor degeneration and therapies for the side effects after photocoagulation.
Beta and Theta Oscillations Correlate With Subjective Time During Musical Improvisation in Ecological and Controlled Settings: A Single Subject Study
Authors: Farrugia Nicolas , Lamouroux Alix , Rocher Christophe , Bouvet Jules , Lioi Giulia
Published: June 2021

In this paper, we describe the results of a single subject study attempting at a better understanding of the subjective mental state during musical improvisation. In a first experiment, we setup an ecological paradigm measuring EEG on a musician in free improvised concerts with an audience, followed by retrospective rating of the mental state of the improviser. We introduce Subjective Temporal Resolution (STR), a retrospective rating assessing the instantaneous quantization of subjective timing of the improviser. We identified high and low STR states using Hidden Markov Models in two performances, and were able to decode those states using supervised learning on instantaneous EEG power spectrum, showing increases in theta and alpha power with high STR values. In a second experiment, we found an increase of theta and beta power when experimentally manipulating STR in a musical improvisation imagery experiment. These results are interpreted with respect to previous research on flow state in creativity, as well as with the temporal processing literature. We suggest that a component of the subjective state of musical improvisation may be reflected in an underlying mechanism related to the subjective quantization of time. We also demonstrate the feasibility of single case studies of musical improvisation using brain activity measurements and retrospective reports, by obtaining consistent results across multiple sessions.