bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Parasitoid of Marine Dinoflagellates, Pararosarium dinoexitiosum gen. et sp. nov. (Perkinsozoa, Alveolata), Showing Characteristic Beaded Sporocytes
Authors: Jeon Boo Seong , Park Myung Gil
Published: December 2021

The phylum Perkinsozoa is known as an exclusively parasitic group within alveolates and is widely distributed in various aquatic environments from marine to freshwater environments. Nonetheless, their morphology, life cycle, the identity of the host, and physiological characteristics remain still poorly understood. During intensive sampling along the west coast of Korea in October and November 2017, a new parasitoid, which shares several characteristics with the extant families Perkinsidae and Parviluciferaceae, was discovered and three strains of the new parasitoid were successfully established in cultures. Cross-infection experiments showed that among the examined planktonic groups, only dinoflagellates were susceptible to the new parasitoid, with infections observed in species belonging to eight genera. Even though the new parasitoid shared many morphological and developmental characteristics with other Perkinsozoan parasites, it differed from them by its densely packed trophocyte structure without a large vacuole or hyaline material during the growth stage. These characteristics are common among Parviluciferaceae members. Furthermore, through palintomic extracellular sporogenesis, it produced characteristic interconnected sporocytes resembling a string of beads. Phylogenetic analyses based on the small subunit and large subunit ribosomal DNA sequences revealed that the new parasitoid was distantly related to the family Parviluciferaceae and was more closely related to the families Perkinsidae and Xcellidae. Morphological, ultrastructural, and molecular data on the new parasitoid raised the need to erect a new family, i.e., Pararosariidae, within the phylum Perkinsozoa with Pararosarium dinoexitiosum gen. et sp. nov. as the type species. The isolation and establishment in culture of the new parasitoid outside the family Parviluciferaceae in the present study would contribute to the better understanding of the diversity of Perkinsozoan parasites and provide useful material for comparisons to other parasite species in the further study.
Bacterial Diversity and CAZyme Potential Revealed in Pandanus Rich Thermal Spring Cluster of India: A Non-cultivable 16S rRNA Sequencing Approach
Authors: Dixit Sangita , Gaur Mahendra , Subudhi Enketeswara , Sahoo Rajesh Kumar , Dey Suchanda , Mahapatra Lakshmi Datta , Mandal Surajit De , Senthil Kumar Nachimuthu , Anirudh Hardik
Published: December 2021

In the present study, we explored four different geothermal spots of the Deulajhari spring cluster at a proximity of 10–20 meters with temperatures of 43 to 65°C to unravel their genesis, bacterial diversity and CAZyme potential. However, minor variations in physicochemical properties; TOC, sodium, chloride, zinc and nitrate were observed, including the pH of the spring openings. Illumina based amplicon sequencing revealed Firmicutes, Proteobacteria and Chloroflexi as the major bacterial phylum with higher abundance in the DJ04 sample. The alpha diversity of all the springs was almost same, whereas beta diversity revealed variations in the degree of uniqueness of OTUs at different temperatures. Statistical analysis established a positive correlation between sulfur content with Heliobacterium, Thermodesulfovibrio, Thermodesulfobacterium and Herpetosipho as well as TOC and HCO3 with Thermoanaerobacter, Desulfovibrio, Candidatus solibacter and Dehalogenimona. The major hydrocarbon family genes and Carbohydrate Active Enzyme pathways were predicted to be highest in DJ04 with elevated concentrations of HCO3 and TOC. Higher homogeneity in geo-physicochemical and microbial features direct the possibility of the common origin of these springs through plumbing systems. However, the minor variations in diversity and functionality were due to variations in temperature in spring openings through the mixing of subsurface water contaminated with carbohydrates from leaf biomass litter. Functional characterization of the thermophilic bacteria of this spring provides essential scope for further industrial applications. The biogeochemical reasons hypothesized for the genesis of unique multiple openings in the cluster are also of interest to conservation scientists for taking measures toward necessary laws and regulations to protect and preserve these springs.
A Review of Ammonia-Oxidizing Archaea and Anaerobic Ammonia-Oxidizing Bacteria in the Aquaculture Pond Environment in China
Authors: Lu Shimin , Liu Xingguo , Liu Chong , Cheng Guofeng , Zhou Runfeng , Li Yayuan
Published: December 2021

The excessive ammonia produced in pond aquaculture processes cannot be ignored. In this review, we present the distribution and diversity of ammonia-oxidizing archaea (AOA) and anaerobic ammonia-oxidizing bacteria (AnAOB) in the pond environment. Combined with environmental conditions, we analyze the advantages of AOA and AnAOB in aquaculture water treatment and discuss the current situation of pond water treatment engineering involving these microbes. AOA and AnAOB play an important role in the nitrogen removal process of aquaculture pond water, especially in seasonal low temperatures and anoxic sediment layers. Finally, we prospect the application of bioreactors to purify pond aquaculture water using AOA and AnAOB, in autotrophic nitrogen removal, which can reduce the production of greenhouse gases (such as nitrous oxide) and is conducive to the development of environmentally sustainable pond aquaculture.
Spatial and Annual Variation in Microbial Abundance, Community Composition, and Diversity Associated With Alpine Surface Snow
Authors: Fillinger Lucas , Hürkamp Kerstin , Stumpp Christine , Weber Nina , Forster Dominik , Hausmann Bela , Schultz Lotta , Griebler Christian
Published: December 2021

Understanding microbial community dynamics in the alpine cryosphere is an important step toward assessing climate change impacts on these fragile ecosystems and meltwater-fed environments downstream. In this study, we analyzed microbial community composition, variation in community alpha and beta diversity, and the number of prokaryotic cells and virus-like particles (VLP) in seasonal snowpack from two consecutive years at three high altitude mountain summits along a longitudinal transect across the European Alps. Numbers of prokaryotic cells and VLP both ranged around 104 and 105 per mL of snow meltwater on average, with variation generally within one order of magnitude between sites and years. VLP-to-prokaryotic cell ratios spanned two orders of magnitude, with median values close to 1, and little variation between sites and years in the majority of cases. Estimates of microbial community alpha diversity inferred from Hill numbers revealed low contributions of common and abundant microbial taxa to the total taxon richness, and thus low community evenness. Similar to prokaryotic cell and VLP numbers, differences in alpha diversity between years and sites were generally relatively modest. In contrast, community composition displayed strong variation between sites and especially between years. Analyses of taxonomic and phylogenetic community composition showed that differences between sites within years were mainly characterized by changes in abundances of microbial taxa from similar phylogenetic clades, whereas shifts between years were due to significant phylogenetic turnover. Our findings on the spatiotemporal dynamics and magnitude of variation of microbial abundances, community diversity, and composition in surface snow may help define baseline levels to assess future impacts of climate change on the alpine cryosphere.
Effect of Chronic Exposure to Textile Wastewater Treatment Plant Effluents on Growth Performance, Oxidative Stress, and Intestinal Microbiota in Adult Zebrafish (Danio rerio)
Authors: Wang Chun , Yuan Zixi , Sun Yingxue , Yao Xiaolong , Li Ruixuan , Li Shuangshuang
Published: December 2021

The ever-increasing production and processing of textiles will lead to greater risks of releasing pollutants into the environment. Textile wastewater treatment plants (TWTPs) effluent are an important source of persistent toxic pollutants in receiving water bodies. The effects of specific pollutants on organisms are usually studied under laboratory conditions, and therefore, comprehensive results are not obtained regarding the chronic combined effects of pollutants under aquatic environmental conditions. Thus, this study aimed to determine the combined effects of TWTP effluents on the growth performance, oxidative stress, inflammatory response, and intestinal microbiota of adult zebrafish (Danio rerio). Exposure to TWTP effluents significantly inhibited growth, exacerbated the condition factor, and increased the mortality of adult zebrafish. Moreover, markedly decreases were observed in the activities of antioxidant enzymes, such as CAT, GSH, GSH-Px, MDA, SOD, and T-AOC, mostly in the intestine and muscle tissues of zebrafish after 1 and 4 months of exposure. In addition, the results demonstrated that TWTP effluent exposure affected the intestinal microbial community composition and decreased community diversity. Slight changes were found in the relative abundance of probiotic Lactobacillus, Akkermansia, and Lactococcus in zebrafish guts after chronic TWTP effluent exposure. The chronic toxic effects of slight increases in opportunistic pathogens, such as Mycoplasma, Stenotrophomonas, and Vibrio, deserve further attention. Our results reveal that TWTP effluent exposure poses potential health risks to aquatic organisms through growth inhibition, oxidative stress impairment of the intestine and muscles, and intestinal microbial community alterations.
The Deep Rocky Biosphere: New Geomicrobiological Insights and Prospects
Authors: Takamiya Hinako , Kouduka Mariko , Suzuki Yohey
Published: December 2021

Rocks that react with liquid water are widespread but spatiotemporally limited throughout the solar system, except for Earth. Rock-forming minerals with high iron content and accessory minerals with high amounts of radioactive elements are essential to support rock-hosted microbial life by supplying organics, molecular hydrogen, and/or oxidants. Recent technological advances have broadened our understanding of the rocky biosphere, where microbial inhabitation appears to be difficult without nutrient and energy inputs from minerals. In particular, microbial proliferation in igneous rock basements has been revealed using innovative geomicrobiological techniques. These recent findings have dramatically changed our perspective on the nature and the extent of microbial life in the rocky biosphere, microbial interactions with minerals, and the influence of external factors on habitability. This study aimed to gather information from scientific and/or technological innovations, such as omics-based and single-cell level characterizations, targeting deep rocky habitats of organisms with minimal dependence on photosynthesis. By synthesizing pieces of rock-hosted life, we can explore the evo-phylogeny and ecophysiology of microbial life on Earth and the life’s potential on other planetary bodies.
Nutrient Regulation of Relative Dominance of Cylindrospermopsin-Producing and Non-cylindrospermopsin-Producing Raphidiopsis raciborskii
Authors: Lei Lamei , Lei Minting , Cheng Nan , Chen Zhijiang , Xiao Lijuan , Han Bo-ping , Lin Qiuqi
Published: December 2021

Raphidiopsis raciborskii (previously Cylindrospermopsis raciborskii) can produce cylindrospermopsin (CYN) which is of great concern due to its considerable toxicity to human and animals. Its CYN-producing (toxic) and non-CYN-producing (non-toxic) strains co-exist commonly in natural water bodies, while how their relative dominance is regulated has not been addressed. In this study, we combined field investigation with laboratory experiments to assessed the relationship between toxic and non-toxic R. raciborskii abundances under different nutrient levels. The rpoC1- and cyrJ-based qPCR was applied for quantifying total and toxic R. raciborskii abundances, respectively. The field survey showed that toxic R. raciborskii was detected in 97 of 115 reservoirs where its proportion ranged from 0.3% to 39.7% within the R. raciborskii population. Both total and toxic R. raciborskii abundances increased significantly with trophic level of these reservoirs, consistent with our monoculture and co-culture experiments showing in an increase in R. raciborskii growth with increasing nitrogen (N) or phosphorus (P) concentrations. In the monoculture experiments, growth rates of non-toxic and toxic strains from Australia or China were not significantly different under the same culture conditions. On the other hand, in the co-culture experiments, the toxic strains displayed a significantly faster growth than non-toxic strains under nutrient-replete conditions, resulting in an obvious shift toward the dominance by toxic strains from day 3 to the end of the experiments, regardless of the strain originating from Australia or China. The reverse was found under N- or P-limited conditions. Our results indicated that the toxic strains of R. raciborskii have a competitive advantage relative to the non-toxic strains in a more eutrophic world. In parallel to an increase in dominance, both toxic strains grown in the mixed population significantly increased CYN production under nutrient-replete conditions as compared to nutrient-limited conditions, suggesting that CYN may be of significance for ecological advantage of toxic R. raciborskii. These results highlight the importance of nutrient availability in regulating abundances and strain dominance of two genotypes of R. raciborskii. Our findings demonstrated that elevated nutrients would favor the growth of CYN-producing R. raciborskii and CYN production, leading to more blooms with higher toxicity at global scale.
The Triangle Relationship Between Long Noncoding RNA, RIG-I-like Receptor Signaling Pathway, and Glycolysis
Authors: Ren Zhihua , Yu Yueru , Chen Chaoxi , Yang Dingyong , Ding Ting , Zhu Ling , Deng Junliang , Xu Zhiwen
Published: December 2021

Long noncoding RNA (LncRNA), a noncoding RNA over 200nt in length, can regulate glycolysis through metabolic pathways, glucose metabolizing enzymes, and epigenetic reprogramming. Upon viral infection, increased aerobic glycolysis providzes material and energy for viral replication. Mitochondrial antiviral signaling protein (MAVS) is the only protein-specified downstream of retinoic acid-inducible gene I (RIG-I) that bridges the gap between antiviral immunity and glycolysis. MAVS binding to RIG-I inhibits MAVS binding to Hexokinase (HK2), thereby impairing glycolysis, while excess lactate production inhibits MAVS and the downstream antiviral immune response, facilitating viral replication. LncRNAs can also regulate antiviral innate immunity by interacting with RIG-I and downstream signaling pathways and by regulating the expression of interferons and interferon-stimulated genes (ISGs). Altogether, we summarize the relationship between glycolysis, antiviral immunity, and lncRNAs and propose that lncRNAs interact with glycolysis and antiviral pathways, providing a new perspective for the future treatment against virus infection, including SARS-CoV-2.
Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview
Authors: Elsayed Liena E. O. , Eltazi Isra Zuhair , Ahmed Ammar E. , Stevanin Giovanni
Published: December 2021

Hereditary spastic paraplegias (HSP) are a heterogeneous group of motor neurodegenerative disorders that have the core clinical presentation of pyramidal syndrome which starts typically in the lower limbs. They can present as pure or complex forms with all classical modes of monogenic inheritance reported. To date, there are more than 100 loci/88 spastic paraplegia genes (SPG) involved in the pathogenesis of HSP. New patterns of inheritance are being increasingly identified in this era of huge advances in genetic and functional studies. A wide range of clinical symptoms and signs are now reported to complicate HSP with increasing overall complexity of the clinical presentations considered as HSP. This is especially true with the emergence of multiple HSP phenotypes that are situated in the borderline zone with other neurogenetic disorders. The genetic diagnostic approaches and the utilized techniques leave a diagnostic gap of 25% in the best studies. In this review, we summarize the known types of HSP with special focus on those in which spasticity is the principal clinical phenotype (“SPGn” designation). We discuss their modes of inheritance, clinical phenotypes, underlying genetics, and molecular pathways, providing some observations about therapeutic opportunities gained from animal models and functional studies. This review may pave the way for more analytic approaches that take into consideration the overall picture of HSP. It will shed light on subtle associations that can explain the occurrence of the disease and allow a better understanding of its observed variations. This should help in the identification of future biomarkers, predictors of disease onset and progression, and treatments for both better functional outcomes and quality of life.
Protein pI and Intracellular Localization
Authors: Tokmakov Alexander A. , Kurotani Atsushi , Sato Ken-Ichi
Published: December 2021

The protein isoelectric point (pI) can be calculated from an amino acid sequence using computational analysis in a good agreement with experimental data. Availability of whole-genome sequences empowers comparative studies of proteome-wide pI distributions. It was found that the whole-proteome distributions of protein pI values are multimodal in different species. It was further hypothesized that the observed multimodality is associated with subcellular localization-specific differences in local pI distributions. Here, we overview the multimodality of proteome-wide pI distributions in different organisms focusing on the relationships between protein pI and subcellular localization. We also discuss the probable factors responsible for variation of the intracellular localization-specific pI profiles.
Modularize and Unite: Toward Creating a Functional Artificial Cell
Authors: Wang Chen , Yang Junzhu , Lu Yuan
Published: December 2021

An artificial cell is a simplified model of a living system, bringing breakthroughs into both basic life science and applied research. The bottom-up strategy instructs the construction of an artificial cell from nonliving materials, which could be complicated and interdisciplinary considering the inherent complexity of living cells. Although significant progress has been achieved in the past 2 decades, the area is still facing some problems, such as poor compatibility with complex bio-systems, instability, and low standardization of the construction method. In this review, we propose creating artificial cells through the integration of different functional modules. Furthermore, we divide the function requirements of an artificial cell into four essential parts (metabolism, energy supplement, proliferation, and communication) and discuss the present researches. Then we propose that the compartment and the reestablishment of the communication system would be essential for the reasonable integration of functional modules. Although enormous challenges remain, the modular construction would facilitate the simplification and standardization of an artificial cell toward a natural living system. This function-based strategy would also broaden the application of artificial cells and represent the steps of imitating and surpassing nature.
Influence of Anemia on Postoperative Cognitive Function in Patients Undergo Hysteromyoma Surgery
Authors: You Zhijian , Chen Lesi , Xu Hongxia , Huang Yidan , Wu Jinglei , Wu Jiaxuan
Published: December 2021

Cognitive dysfunction is a common disease in aging population. This study aims to compare the influence of different degrees of anemia on the cognitive function of patients undergo hysteromyoma surgery. Sixty-one patients aged 18–60 years who underwent uterine fibroid surgery in the Second Affiliated Hospital of Shantou University Medical College from March 2019 to December 2020 were selected for this study. Patients were divided into three groups: group normal (Group N, patients have no anemia), group of mild anemia (Group Mi, patients have mild anemia) and group of moderate anemia (Group Mo, patients had moderate anemia). Combined spinal and epidural anesthesia were administered. Cognitive function tests were performed 1 day before the surgery and repeated at the 5th and 30th days after surgery. Peripheral venous blood samples from patients were collected before the surgery, right after surgery and at the 24th and 72nd hours after surgery. The contents of S-100β, IL-6, TNF-α and IL-1β in serum samples were determined by ELISA. It was found that there were no significant differences in general characteristics of patients among Group N, Group Mi and Group Mo (p > 0.05). Nine patients developed postoperative cognitive dysfunction after surgery, and the incidence was 14.75% (9/61). The incidence of postoperative cognitive dysfunction (POCD) was 40% in Group Mo, which was higher than that in Group N and Group Mi. The difference was statistically significant (p < 0.05). Inflammatory factors in patients with POCD were higher in post-surgery than before-surgery (p < 0.05), while there was no statistical significance in the difference of inflammatory factors of patients without POCD before and after surgery (p > 0.05). Taken together, this study suggested that moderate anemia could be a risk factor of POCD in patients undergoing hysteromyoma surgeries. This study will help surgeons developing measures for preventing the occurrence of POCD.
ARMC Subfamily: Structures, Functions, Evolutions, Interactions, and Diseases
Authors: Huang Yutao , Jiang Zijian , Gao Xiangyu , Luo Peng , Jiang Xiaofan
Published: December 2021

Armadillo repeat-containing proteins (ARMCs) are widely distributed in eukaryotes and have important influences on cell adhesion, signal transduction, mitochondrial function regulation, tumorigenesis, and other processes. These proteins share a similar domain consisting of tandem repeats approximately 42 amino acids in length, and this domain constitutes a substantial platform for the binding between ARMCs and other proteins. An ARMC subfamily, including ARMC1∼10, ARMC12, and ARMCX1∼6, has received increasing attention. These proteins may have many terminal regions and play a critical role in various diseases. On the one hand, based on their similar central domain of tandem repeats, this ARMC subfamily may function similarly to other ARMCs. On the other hand, the unique domains on their terminals may cause these proteins to have different functions. Here, we focus on the ARMC subfamily (ARMC1∼10, ARMC12, and ARMCX1∼6), which is relatively conserved in vertebrates and highly conserved in mammals, particularly primates. We review the structures, biological functions, evolutions, interactions, and related diseases of the ARMC subfamily, which involve more than 30 diseases and 40 bypasses, including interactions and relationships between more than 100 proteins and signaling molecules. We look forward to obtaining a clearer understanding of the ARMC subfamily to facilitate further in-depth research and treatment of related diseases.
Younger and Late Middle-Aged Adults Exhibit Different Patterns of Cognitive-Motor Interference During Locomotor Adaptation, With No Disruption of Savings
Authors: Rossi Cristina , Roemmich Ryan T. , Schweighofer Nicolas , Bastian Amy J. , Leech Kristan A.
Published: December 2021

It has been proposed that motor adaptation and subsequent savings (or faster relearning) of an adapted movement pattern are mediated by cognitive processes. Here, we evaluated the pattern of cognitive-motor interference that emerges when young and late middle-aged adults perform an executive working memory task during locomotor adaptation. We also asked if this interferes with savings of a newly learned walking pattern, as has been suggested by a study of reaching adaptation. We studied split-belt treadmill adaptation and savings in young (21 ± 2 y/o) and late middle-aged (56 ± 6 y/o) adults with or without a secondary 2-back task during adaptation. We found that young adults showed similar performance on the 2-back task during baseline and adaptation, suggesting no effect of the dual-task on cognitive performance; however, dual-tasking interfered with adaptation over the first few steps. Conversely, dual-tasking caused a decrement in cognitive performance in late middle-aged adults with no effect on adaptation. To determine if this effect was specific to adaptation, we also evaluated dual-task interference in late middle-aged adults that dual-tasked while walking in a complex environment that did not induce motor adaptation. This group exhibited less cognitive-motor interference than late middle-aged adults who dual-tasked during adaptation. Savings was unaffected by dual-tasking in both young and late middle-aged adults, which may indicate different underlying mechanisms for savings of reaching and walking. Collectively, our findings reveal an age-dependent effect of cognitive-motor interference during dual-task locomotor adaptation and no effect of dual-tasking on savings, regardless of age. Young adults maintain cognitive performance and show a mild decrement in locomotor adaptation, while late middle-aged adults adapt locomotion at the expense of cognitive performance.
Magnetoencephalography Brain Signatures Relate to Cognition and Cognitive Reserve in the Oldest-Old: The EMIF-AD 90 + Study
Authors: Griffa Alessandra , Legdeur Nienke , Badissi Maryam , van den Heuvel Martijn P. , Stam Cornelis J. , Visser Pieter Jelle , Hillebrand Arjan
Published: December 2021

The oldest-old subjects represent the fastest growing segment of society and are at high risk for dementia with a prevalence of up to 40%. Lifestyle factors, such as lifelong participation in cognitive and leisure activities, may contribute to individual cognitive reserve and reduce the risk for cognitive impairments. However, the neural bases underlying cognitive functioning and cognitive reserve in this age range are still poorly understood. Here, we investigate spectral and functional connectivity features obtained from resting-state MEG recordings in a cohort of 35 cognitively normal (92.2 ± 1.8 years old, 19 women) and 11 cognitively impaired (90.9 ± 1.9 years old, 1 woman) oldest-old participants, in relation to cognitive traits and cognitive reserve. The latter was approximated with a self-reported scale on lifelong engagement in cognitively demanding activities. Cognitively impaired oldest-old participants had slower cortical rhythms in frontal, parietal and default mode network regions compared to the cognitively normal subjects. These alterations mainly concerned the theta and beta band and partially explained inter-subject variability of episodic memory scores. Moreover, a distinct spectral pattern characterized by higher relative power in the alpha band was specifically associated with higher cognitive reserve while taking into account the effect of age and education level. Finally, stronger functional connectivity in the alpha and beta band were weakly associated with better cognitive performances in the whole group of subjects, although functional connectivity effects were less prominent than the spectral ones. Our results shed new light on the neural underpinnings of cognitive functioning in the oldest-old population and indicate that cognitive performance and cognitive reserve may have distinct spectral electrophysiological substrates.
Active Life for Brain Health: A Narrative Review of the Mechanism Underlying the Protective Effects of Physical Activity on the Brain
Authors: Umegaki Hiroyuki , Sakurai Takashi , Arai Hidenori
Published: December 2021

A growing body of evidence clearly indicates the beneficial effects of physical activity (PA) on cognition. The importance of PA is now being reevaluated due to the increase in sedentary behavior in older adults during the COVID-19 pandemic. Although many studies in humans have revealed that PA helps to preserve brain health, the underlying mechanisms have not yet been fully elucidated. In this review, which mainly focuses on studies in humans, we comprehensively summarize the mechanisms underlying the beneficial effects of PA or exercise on brain health, particularly cognition. The most intensively studied mechanisms of the beneficial effects of PA involve an increase in brain-derived neurotrophic factor (BDNF) and preservation of brain volume, especially that of the hippocampus. Nonetheless, the mutual associations between these two factors remain unclear. For example, although BDNF presumably affects brain volume by inhibiting neuronal death and/or increasing neurogenesis, human data on this issue are scarce. It also remains to be determined whether PA modulates amyloid and tau metabolism. However, recent advances in blood-based biomarkers are expected to help elucidate the beneficial effects of PA on the brain. Clinical data suggest that PA functionally modulates cognition independently of neurodegeneration, and the mechanisms involved include modulation of functional connectivity, neuronal compensation, neuronal resource allocation, and neuronal efficiency. However, these mechanisms are as yet not fully understood. A clear understanding of the mechanisms involved could help motivate inactive persons to change their behavior. More accumulation of evidence in this field is awaited.
Safety and Efficacy of Rapamycin-Eluting Vertebral Stents in Patients With Symptomatic Extracranial Vertebral Artery Stenosis
Authors: Ma Gaoting , Song Ligang , Ma Ning , Raynald  , Shuai Jie , Wu Wei , Wan Jieqing , Zhao Zhenwei , Li Guangjian , Yin Sen , Ding Shenghao , Li Jiang , Jia Baixue , Tong Xu , Mo Dapeng , Gao Feng , Sun Xuan , Deng Yiming , Huo Xiaochuan , Li Wei , Chen Kangning , Miao Zhongrong
Published: December 2021

Background and Purpose: Drug-eluting stents generally have superior performance to bare metal stents in the treatment of vertebral artery stenosis (VAS). This prospective, multicenter, and single-arm clinical trial was initiated to assess in-stent restenosis (ISR) and midterm outcome after rapamycin-eluting stent placement in patients with symptomatic extracranial VAS.

Methods: The subjects underwent angiographic follow-up at 6 months and final clinical follow-up at 12 months. The primary efficacy endpoint was ISR at 6 months. Secondary endpoints included technical success, target lesion-related transient ischemic attack (TIA), stroke, or death, and all-cause TIA, stroke, or death during the 12-month follow-up period.

Results: A total of 104 stents were implanted in the 101 patients and 83 patients (82.2%) completed angiographic follow-up at 6 months. The technical success rate was 86.1% (87/101); mean in-stent stenosis rate was 25.1 ± 17.1% and ISR rate was 5.9% (95% CI: 0.8–10.9%). All the patients with ISR were completely asymptomatic and no stent fractures were observed during angiographic follow-up. At the 12-month clinical follow-up, target lesion-related TIA, stroke, or death had occurred in two (2.0%) patients and all-cause TIA, stroke, or death had occurred in six (6.1%) patients.

Conclusion: The placement of rapamycin-eluting stents in patients with symptomatic extracranial VAS yields favorable ISR results and showed a trend of favorable safety outcomes including low rates of perioperative complications and late stroke. However, further study is needed to establish the long-term clinical benefits of this stent in the treatment of VA disease.
Hemorrhagic Transformation After Ischemic Stroke: Mechanisms and Management
Authors: Hong Ji Man , Kim Da Sol , Kim Min
Published: December 2021

Symptomatic hemorrhagic transformation (HT) is one of the complications most likely to lead to death in patients with acute ischemic stroke. HT after acute ischemic stroke is diagnosed when certain areas of cerebral infarction appear as cerebral hemorrhage on radiological images. Its mechanisms are usually explained by disruption of the blood-brain barrier and reperfusion injury that causes leakage of peripheral blood cells. In ischemic infarction, HT may be a natural progression of acute ischemic stroke and can be facilitated or enhanced by reperfusion therapy. Therefore, to balance risks and benefits, HT occurrence in acute stroke settings is an important factor to be considered by physicians to determine whether recanalization therapy should be performed. This review aims to illustrate the pathophysiological mechanisms of HT, outline most HT-related factors after reperfusion therapy, and describe prevention strategies for the occurrence and enlargement of HT, such as blood pressure control. Finally, we propose a promising therapeutic approach based on biological research studies that would help clinicians treat such catastrophic complications.
Anatomic Variation of the Lateral Sinus in Patients With Idiopathic Intracranial Hypertension: Delineation With Black-Blood Contrast-Enhanced MRI
Authors: Tian Yu , Zhang Zhe , Jing Jing , Dong Kehui , Mo Dapeng , Wang Yilong
Published: December 2021

Objectives: The purpose of this study was to describe the peculiar anatomic variations in the lateral sinus and analyze the patterns of cerebrospinal fluid (CSF) drainage by using high-resolution (HR) black-blood (BB) contrast-enhanced magnetic resonance imaging (MRI) in patients with idiopathic intracranial hypertension (IIH).

Methods: Total 33 IIH patients who were found cerebral venous sinus stenosis (CVSS) by MR venography (MRV) were enrolled in this study. HR-BB contrast-enhanced MRI was used to assess the features of anatomical variations in transverse sinus and sigmoid sinus. The development of bilateral sinuses was firstly evaluated, including unilateral hypoplasia with contralateral dominance or bilateral balanced development. Then, four kinds of anatomical variations were eventually recorded, including circumscribed stenosis, arachnoid granulation (AG), fibrous septum (FS), and brain herniation (BH) into dural venous sinus (DVS).

Results: Bilateral venous drainage dysfunction was found in 30(90.9%) patients, whereas only 3(9.1%) patients presented unilateral venous drainage dysfunction. There was no difference in clinical symptoms between the two groups. The most common case is hypoplasia in unilateral sinus combined with anatomic variation in the contralateral dominant transverse sinus such as AG and BH into DVS. Total of 52 anatomic variations were finally found in bilateral sinuses in 33 enrolled patients, including 19(36.5%)AGs, 12(23.1%)FS, 7(13.5%) BH into DVS and 14(26.9%) circumscribed stenoses. Moreover, 41(62.1%) lateral sinuses showed enhancement in T1-weight-enhanced MRI.

Conclusions: Patients with CVSS almost had CSF outflow disorders, whatever bilateral equalization or unilateral hypoplasia with contralateral dominance. Four types of main anatomic variations, including circumscribed stenosis, AG, FS, and BH into DVS, caused venous reflux obstruction by elevating the intracranial press (ICP).
Suicide in Older Adult Men Is Not Related to a Personal History of Participation in Football
Authors: Iverson Grant L. , Deep-Soboslay Amy , Hyde Thomas M. , Kleinman Joel E. , Erskine Brittany , Fisher-Hubbard Amanda , deJong Joyce L. , Castellani Rudolph J.
Published: December 2021

Introduction: It is reasonable to estimate that tens of millions of men in the United States played high school football. There is societal concern that participation in football confers risk for later-in-life mental health problems. The purpose of this study is to examine whether there is an association between a personal history of playing high school football and death by suicide.

Methods: The subjects were obtained from the Lieber Institute for Brain Development (LIBD) brain donation program in collaboration with the Office of the Medical Examiner at Western Michigan University Homer Stryker MD School of Medicine. Donor history was documented via medical records, mental health records, and telephone interviews with the next-of-kin.

Results: The sample included 198 men aged 50 or older (median = 65.0 years, interquartile range = 57–75). There were 34.8% who participated in contact sports during high school (including football), and 29.8% participated in high school football. Approximately one-third of the sample had suicide as their manner of death (34.8%). There was no statistically significant difference in the proportions of suicide as a manner of death among those men with a personal history of playing football compared to men who did not play football or who did not play sports (p = 0.070, Odds Ratio, OR = 0.537). Those who played football were significantly less likely to have a lifetime history of a suicide attempt (p = 0.012, OR = 0.352). Men with mood disorders (p < 0.001, OR = 10.712), substance use disorders (p < 0.020, OR = 2.075), and those with a history of suicide ideation (p < 0.001, OR = 8.038) or attempts (p < 0.001, OR = 40.634) were more likely to have suicide as a manner of death. Moreover, those men with a family history of suicide were more likely to have prior suicide attempts (p = 0.031, OR = 2.153) and to have completed suicide (p = 0.001, OR = 2.927).

Discussion: Suicide was related to well-established risk factors such as a personal history of a mood disorder, substance abuse disorder, prior suicide ideation, suicide attempts, and a family history of suicide attempts. This study adds to a steadily growing body of evidence suggesting that playing high school football is not associated with increased risk for suicidality or suicide during adulthood.
Cost-Consequence Analysis of Advanced Imaging in Acute Ischemic Stroke Care
Authors: Boltyenkov Artem T. , Martinez Gabriela , Pandya Ankur , Katz Jeffrey M. , Wang Jason J. , Naidich Jason J. , Rula Elizabeth , Sanelli Pina C.
Published: December 2021

Introduction: The purpose of this study was to illustrate the potential costs and health consequences of implementing advanced CT angiography and perfusion (CTAP) as the initial imaging in patients presenting with acute ischemic stroke (AIS) symptoms at a comprehensive stroke center (CSC).

Methods: A decision-simulation model based on the American Heart Association's recommendations for AIS care pathways was developed to assess imaging strategies for a 5-year period from the institutional perspective. The following strategies were compared: (1) advanced CTAP imaging: NCCT + CTA + CT perfusion at the time of presentation; (2) standard-of-care: non-contrast CT (NCCT) at the time of presentation, with CT angiography (CTA) ± CT perfusion only in select patients (initial imaging to exclude hemorrhage and extensive ischemia) for mechanical thrombectomy (MT) evaluation. Model parameters were defined with evidence-based data. Cost-consequence and sensitivity analyses were performed. The modified Rankin Scale (mRS) at 90 days was used as the outcome measure.

Results: The decision-simulation modeling revealed that adoption of the advanced CTAP imaging increased per-patient imaging costs by 1.19% ($9.28/$779.72), increased per-patient treatment costs by 33.25% ($729.96/$2,195.24), and decreased other per-patient acute care costs by 0.7% (–$114.12/$16,285.85). The large increase in treatment costs was caused by higher proportion of patients being treated. However, improved outcomes lowered the other per-patient acute care costs. Over the five-year period, advanced CTAP imaging led to 1.63% (66/4,040) more patients with good outcomes (90-day mRS 0-2), 2.23% (66/2,960) fewer patients with poor outcomes (90-day mRS 3-5), and no change in mortality (90-day mRS 6). Our CT equipment utilization analysis showed that the demand for CT equipment in terms of scanner time (minutes) was 24% lower in the advanced CTAP imaging strategy compared to the standard-of-care strategy. The number of EVT procedures performed at the CSC may increase by 50%.

Conclusions: Our study reveals that adoption of advanced CTAP imaging at presentation increases the demand for treatment of acute ischemic stroke patients as more patients are diagnosed within the treatment time window compared to standard-of-care imaging. Advanced imaging also leads to more patients with good functional outcomes and fewer patients with dependent functional status.
Ontogeny of the Projections From the Dorsomedial Division of the Anterior Bed Nucleus of the Stria Terminalis to Hypothalamic Nuclei
Authors: Lanzillo Marc , Gervais Manon , Croizier Sophie
Published: December 2021

The bed nucleus of the stria terminalis (BNST) is a telencephalic structure well-connected to hypothalamic regions known to control goal-oriented behaviors such as feeding. In particular, we showed that the dorsomedial division of the anterior BNST innervate neurons of the paraventricular (PVH), dorsomedial (DMH), and arcuate (ARH) hypothalamic nuclei as well as the lateral hypothalamic area (LHA). While the anatomy of these projections has been characterized in mice, their ontogeny has not been studied. In this study, we used the DiI-based tract tracing approach to study the development of BNST projections innervating several hypothalamic areas including the PVH, DMH, ARH, and LHA. These results indicate that projections from the dorsomedial division of the anterior BNST to hypothalamic nuclei are immature at birth and substantially reach the PVH, DMH, and the LHA at P10. In the ARH, only sparse fibers are observed at P10, but their density increased markedly between P12 and P14. Collectively, these findings provide new insight into the ontogeny of hypothalamic circuits, and highlight the importance of considering the developmental context as a direct modulator in their proper formation.
Transcutaneous Auricular Vagus Nerve Stimulation (tAVNS) Delivered During Upper Limb Interactive Robotic Training Demonstrates Novel Antagonist Control for Reaching Movements Following Stroke
Authors: Chang Johanna L. , Coggins Ashley N. , Saul Maira , Paget-Blanc Alexandra , Straka Malgorzata , Wright Jason , Datta-Chaudhuri Timir , Zanos Stavros , Volpe Bruce T.
Published: December 2021

Implanted vagus nerve stimulation (VNS) delivered concurrently with upper limb rehabilitation has been shown to improve arm function after stroke. Transcutaneous auricular VNS (taVNS) offers a non-invasive alternative to implanted VNS and may provide similar therapeutic benefit. There is much discussion about the optimal approach for combining VNS and physical therapy, as such we sought to determine whether taVNS administered during robotic training, specifically delivered during the premotor planning stage for arm extension movements, would confer additional motor improvement in patients with chronic stroke. Thirty-six patients with chronic, moderate-severe upper limb hemiparesis (>6 months; mean Upper Extremity Fugl-Meyer score = 25 ± 2, range 13–48), were randomized to receive 9 sessions (1 h in length, 3x/week for 3 weeks) of active (N = 18) or sham (N = 18) taVNS (500 ms bursts, frequency 30 Hz, pulse width 0.3 ms, max intensity 5 mA, ∼250 stimulated movements per session) delivered during robotic training. taVNS was triggered by the onset of a visual cue prior to center-out arm extension movements. Clinical assessments and surface electromyography (sEMG) measures of the biceps and triceps brachii were collected during separate test sessions. Significant motor improvements were measured for both the active and sham taVNS groups, and these improvements were robust at 3 month follow-up. Compared to the sham group, the active taVNS group showed a significant reduction in spasticity of the wrist and hand at discharge (Modified Tardieu Scale; taVNS = –8.94% vs. sham = + 2.97%, p < 0.05). The EMG results also demonstrated significantly increased variance for the bicep peak sEMG amplitude during extension for the active taVNS group compared to the sham group at discharge (active = 26.29% MVC ± 3.89, sham = 10.63% MVC ± 3.10, mean absolute change admission to discharge, p < 0.01), and at 3-month follow-up, the bicep peak sEMG amplitude was significantly reduced in the active taVNS group (P < 0.05). Thus, robot training improved the motor capacity of both groups, and taVNS, decreased spasticity. taVNS administered during premotor planning of movement may play a role in improving coordinated activation of the agonist-antagonist upper arm muscle groups by mitigating spasticity and increasing motor control following stroke.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier (NCT03592745).
GABAA Receptor Subunit Composition Drives Its Sensitivity to the Insecticide Fipronil
Authors: Soualah Zineb , Taly Antoine , Crespin Lucille , Saulais Ophélie , Henrion Daniel , Legendre Claire , Tricoire-Leignel Hélène , Legros Christian , Mattei César
Published: December 2021

Fipronil (FPN) is a worldwide-used neurotoxic insecticide, targeting, and blocking GABAA receptors (GABAARs). Beyond its efficiency on insect GABAARs, FPN causes neurotoxic effects in humans and mammals. Here, we investigated the mode of action of FPN on mammalian α6-containing GABAARs to understand its inhibitory effects on GABA-induced currents, as a function of the synaptic or extrasynaptic localization of GABAARs. We characterized the effects of FPN by electrophysiology using Xenopus oocytes which were microtransplanted with cerebellum membranes or injected with α6β3, α6β3γ2S (synaptic), and α6β3δ (extrasynaptic) cDNAs. At micromolar concentrations, FPN dose-dependently inhibited cerebellar GABA currents. FPN acts as a non-competitive antagonist on ternary receptors. Surprisingly, the inhibition of GABA-induced currents was partial for extra-synaptic (α6β3δ) and binary (α6β3) receptors, while synaptic α6β3γ2S receptors were fully blocked, indicating that the complementary γ or δ subunit participates in FPN-GABAAR interaction. FPN unexpectedly behaved as a positive modulator on β3 homopentamers. These data show that FPN action is driven by the subunit composition of GABAARs—highlighting the role of the complementary subunit—and thus their localization within a physiological synapse. We built a docking model of FPN on GABAARs, which reveals two putative binding sites. This is consistent with a double binding mode of FPN on GABAARs, possibly one being of high affinity and the other of low affinity. Physiologically, the γ/δ subunit incorporation drives its inhibitory level and has important significance for its toxicity on the mammalian nervous system, especially in acute exposure.