bluuebunny/crossref_metadata_2025 huggingface dataset:
Alkalihalobacterium elongatum gen. nov. sp. nov.: An Antibiotic-Producing Bacterium Isolated From Lonar Lake and Reclassification of the Genus Alkalihalobacillus Into Seven Novel Genera
Authors: Joshi Amaraja , Thite Sonia , Karodi Prachi , Joseph Neetha , Lodha Tushar
Published: October 2021

A Gram-stain positive, long, rod-shaped, motile, and spore-forming bacterium (MEB199T) was isolated from a sediment sample collected from Lonar Lake, India. The strain was oxidase and catalase positive. The strain grew optimally at pH 10, NaCl concentration of 3.5% at 37°C. The major fatty acids were iso-C15:0, iso-C16:0, anteiso-C15:0, and iso-C17:0. The peptidoglycan contained meso-diaminopimelic acid (meso-DAP). Phosphatidylethanolamine, diphosphatidylglycerol, and phosphatidylglycerol were the major polar lipids of MEB199T. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain MEB199T belonged to the family Bacillaceae and exhibited a distinctive position among the members of the genus Alkalihalobacillus (Ahb.). Strain MEB199T shared the highest 16S rRNA gene sequence similarity with Alkalihalobacillus alkalinitrilicus ANL-iso4T (98.36%), whereas with type species Ahb. alcalophilus DSM 485T, it is 94.91%, indicating that strain MEB199T is distinctly related to the genus Alkalihalobacillus. The G + C content of genomic DNA was 36.47 mol%. The digital DNA–DNA hybridization (dDDH) (23.6%) and average nucleotide identity (ANI) (81%) values between strain MEB199T and Ahb. alkalinitrilicus ANL-iso4T confirmed the novelty of this new species. The pairwise identity based on the 16S rRNA gene sequence between the species of genus Alkalihalobacillus ranges from 87.4 to 99.81% indicating the heterogeneity in the genus. The different phylogenetic analysis based on the genome showed that the members of the genus Alkalihalobacillus separated into eight distinct clades. The intra-clade average amino acid identity (AAI) and percentage of conserved proteins (POCP) range from 52 to 68% and 37 to 59%, respectively, which are interspersed on the intra-genera cutoff values; therefore, we reassess the taxonomy of genus Alkalihalobacillus. The phenotypic analysis also corroborated the differentiation between these clades. Based on the phylogenetic analysis, genomic indices, and phenotypic traits, we propose the reclassification of the genus Alkalihalobacillus into seven new genera for which the names Alkalihalobacterium gen. nov., Halalkalibacterium gen. nov., Halalkalibacter gen. nov., Shouchella gen. nov., Pseudalkalibacillus gen. nov., Alkalicoccobacillus gen. nov., and Alkalihalophilus gen. nov. are proposed and provide an emended description of Alkalihalobacillus sensu stricto. Also, we propose the Ahb. okuhidensis as a heterotypic synonym of Alkalihalobacillus halodurans. Based on the polyphasic taxonomic analysis, strain MEB199T represents a novel species of newly proposed genus for which the name Alkalihalobacterium elongatum gen. nov. sp. nov. is proposed. The type strain is MEB199T (= MCC 2982T, = JCM 33704T, = NBRC 114256T, = CGMCC 1.17254T).
Non-thermal Plasma Treatment of ESKAPE Pathogens: A Review
Authors: Scholtz Vladimír , Vaňková Eva , Kašparová Petra , Premanath Ramya , Karunasagar Iddya , Julák Jaroslav
Published: October 2021

The acronym ESKAPE refers to a group of bacteria consisting of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. They are important in human medicine as pathogens that show increasing resistance to commonly used antibiotics; thus, the search for new effective bactericidal agents is still topical. One of the possible alternatives is the use of non-thermal plasma (NTP), a partially ionized gas with the energy stored particularly in the free electrons, which has antimicrobial and anti-biofilm effects. Its mechanism of action includes the formation of pores in the bacterial membranes; therefore, resistance toward it is not developed. This paper focuses on the current overview of literature describing the use of NTP as a new promising tool against ESKAPE bacteria, both in planktonic and biofilm forms. Thus, it points to the fact that NTP treatment can be used for the decontamination of different types of liquids, medical materials, and devices or even surfaces used in various industries. In summary, the use of diverse experimental setups leads to very different efficiencies in inactivation. However, Gram-positive bacteria appear less susceptible compared to Gram-negative ones, in general.
Monitoring Tritrophic Biocontrol Interactions Between Bacillus spp., Fusarium oxysporum f. sp. cubense, Tropical Race 4, and Banana Plants in vivo Based on Fluorescent Transformation System
Authors: He Ping , Li Shu , Xu Shengtao , Fan Huacai , Wang Yongfen , Zhou Wei , Fu Gang , Han Guangyu , Wang Yun-Yue , Zheng Si-Jun
Published: October 2021

Bacillus spp. is effective biocontrol agents for Fusarium wilt of banana (FWB), tropical race 4 (TR4). This study explores the colonization by Bacillus subtilis, Bacillus velezensis, and Bacillus amyloliquefaciens of host banana plants and elucidates the mechanism of antagonistic TR4 biocontrol. The authors selected one B. subtilis strain, three B. velezensis strains, and three B. amyloliquefaciens strains that are proven to significantly inhibit TR4 in vitro, optimized the genetic transformation conditions and explored their colonization process in banana plants. The results showed that we successfully constructed an optimized fluorescent electro-transformation system (OD600 of bacteria concentration=0.7, plasmid concentration=50ng/μl, plasmid volume=2μl, transformation voltage=1.8kV, and transformation capacitance=400Ω) of TR4-inhibitory Bacillus spp. strains. The red fluorescent protein (RFP)-labeled strains were shown to have high stability with a plasmid-retention frequency above 98%, where bacterial growth rates and TR4 inhibition are unaffected by fluorescent plasmid insertion. In vivo colonizing observation by Laser Scanning Confocal Microscopy (LSCM) and Scanning Electron Microscopy (SEM) showed that Bacillus spp. can colonize the internal cells of banana plantlets roots. Further, fluorescent observation by LSCM showed these RFP-labeled bacteria exhibit chemotaxis (chemotaxis ratio was 1.85±0.04) toward green fluorescent protein (GFP)-labeled TR4 hyphae in banana plants. We conclude that B. subtilis, B. velezensis, and B. amyloliquefaciens can successfully colonize banana plants and interact with TR4. Monitoring its dynamic interaction with TR4 and its biocontrol mechanism is under further study.
Reduced Feeding Frequency Improves Feed Efficiency Associated With Altered Fecal Microbiota and Bile Acid Composition in Pigs
Authors: Yan Honglin , Wei Wenzhuo , Hu Luga , Zhang Yong , Zhang Hongfu , Liu Jingbo
Published: October 2021

A biphasic feeding regimen exerts an improvement effect on feed efficiency of pigs. While gut microbiome and metabolome are known to affect the host phenotype, so far the effects of reduced feeding frequency on fecal microbiota and their metabolism in pigs remain unclear. Here, the combination of 16S rRNA sequencing technique as well as untargeted and targeted metabolome analyses was adopted to investigate the fecal microbiome and metabolome of growing–finishing pigs in response to a biphasic feeding [two meals per day (M2)] pattern. Sixty crossbred barrows were randomly assigned into two groups with 10 replicates (three pigs/pen), namely, the free-access feeding group (FA) and the M2 group. Pigs in the FA group were fed free access while those in the M2 group were fed ad libitum twice daily for 1 h at 8:00 and 18:00. Results showed that pigs fed biphasically exhibited increased feed efficiency compared to FA pigs. The Shannon and Simpson indexes were significantly increased by reducing the feeding frequency. In the biphasic-fed pigs, the relative abundances of Subdoligranulum, Roseburia, Mitsuokella, and Terrisporobacter were significantly increased while the relative abundances of unidentified_Spirochaetaceae, Methanobrevibacter, unidentified_Bacteroidales, Alloprevotella, Parabacteroides, and Bacteroides were significantly decreased compared to FA pigs. Partial least-square discriminant analysis (PLS-DA) analysis revealed an obvious variation between the FA and M2 groups; the differential features were mainly involved in arginine, proline, glycine, serine, threonine, and tryptophan metabolism as well as primary bile acid (BA) biosynthesis. In addition, the changes in the microbial genera were correlated with the differential fecal metabolites. A biphasic feeding regimen significantly increased the abundances of primary BAs and secondary BAs in feces of pigs, and the differentially enriched BAs were positively correlated with some specific genera. Taken together, these results suggest that the improvement effect of a reduced feeding frequency on feed efficiency of pigs might be associated with the altered fecal microbial composition and fecal metabolite profile in particular the enlarged stool BA pool.
Mechanically Activated Calcium Channel PIEZO1 Modulates Radiation-Induced Epithelial-Mesenchymal Transition by Forming a Positive Feedback With TGF-β1
Authors: Huang Jia-Qi , Zhang Hao , Guo Xue-Wei , Lu Yan , Wang Si-Nian , Cheng Bo , Dong Su-He , Lyu Xiao-Li , Li Feng-Sheng , Li Yong-Wang
Published: October 2021

TGF-β-centered epithelial-mesenchymal transition (EMT) is a key process involved in radiation-induced pulmonary injury (RIPI) and pulmonary fibrosis. PIEZO1, a mechanosensitive calcium channel, is expressed in myeloid cell and has been found to play an important role in bleomycin-induced pulmonary fibrosis. Whether PIEZO1 is related with radiation-induced EMT remains elusive. Herein, we found that PIEZO1 is functional in rat primary type II epithelial cells and RLE-6TN cells. After irradiation, PIEZO1 expression was increased in rat lung alveolar type II epithelial cells and RLE-6TN cell line, which was accompanied with EMT changes evidenced by increased TGF-β1, N-cadherin, Vimentin, Fibronectin, and α-SMA expression and decreased E-cadherin expression. Addition of exogenous TGF-β1 further enhanced these phenomena in vitro. Knockdown of PIEZO1 partly reverses radiation-induced EMT in vitro. Mechanistically, we found that activation of PIEZO1 could upregulate TGF-β1 expression and promote EMT through Ca2+/HIF-1α signaling. Knockdown of HIF-1α partly reverses enhanced TGF-β1 expression caused by radiation. Meanwhile, the expression of PIEZO1 was up-regulated after TGF-β1 co-culture, and the mechanism could be traced to the inhibition of transcription factor C/EBPβ expression by TGF-β1. Irradiation also caused a decrease in C/EBPβ expression in RLE-6TN cells. Dual luciferase reporter assay and chromatin immunoprecipitation assay (ChIP) confirmed that C/EBPβ represses PIEZO1 expression by binding to the PIEZO1 promoter. Furthermore, overexpression of C/EBPβ by using the synonymous mutation to C/EBPβ siRNA could reverse siRNA-induced upregulation of PIEZO1. In summary, our research suggests a critical role of PIEZO1 signaling in radiation-induced EMT by forming positive feedback with TGF-β1.
Comprehensive Pan-Cancer Analysis of Heat Shock Protein 110, 90, 70, and 60 Families
Authors: Yan Li-rong , Shen Shi-xuan , Wang Ang , Ding Han-xi , Liu Ying-nan , Yuan Yuan , Xu Qian
Published: October 2021

Background:Here we carried out a panoramic analysis of the expression and prognosis of HSP110, HSP90, HSP70, and HSP60 families in 33 types of cancer, with the aim of deepening the systematic understanding of heat shock proteins (HSPs) in cancer.

Materials and Methods:Next-generation sequencing data of multiple tumors were downloaded from TCGA, CCLE and Oncomine databases. RStudio 3.6.1 was used to analyze HSP110, HSP90, HSP70 and HSP60 families based on their expression in 33 types of cancer. The validationsin vivo(stomach adenocarcinoma and colon adenocarcinoma tissues) were performed by qRT-PCR.

Results:HSPs were differentially expressed in different cancers. The results revealed mainly positive correlations among the expressions of HSPs in different cancers. Expressions of HSP family members were generally associated with poor prognosis in respiratory, digestive, urinary and reproductive system tumors and associated with good prognosis in cholangiocarcinoma, pheochromocytoma and paraganglioma. TCGA mutation analysis showed that HSP gene mutation rate in cancers was 0–23%. CCLE mutation analysis indicated that HSP gene mutation rate in 828 cell lines from 15 tumors was 0–17%. CNV analysis revealed that HSPs have different degrees of gene amplifications and deletions in cancers. Gene mutations of 15 HSPs influenced their protein expressions in different cancers. Copy number amplifications and deletions of 22 HSPs also impacted protein expression levels in pan-cancer. HSP gene mutation was generally a poor prognosis factor in cancers, except for uterine corpus endometrial carcinoma. CNVs in 14 HSPs showed varying influences on survival status in different cancers. HSPs may be involved in the activation and inhibition of multiple cancer-related pathways. HSP expressions were closely correlated with 22 immune cell infiltrations in different cancers. The qRT-PCR validation resultsin vivoshowed that HSPA2 was down-regulated in stomach adenocarcinoma and colon adenocarcinoma; HSPA7 and HSPA1A also were down-regulated in colon adenocarcinoma. HSPA2-HSPA7 (r = 0.031,p= 0.009) and HSPA1A-HSPA7 (r = 0.516,p< 0.001) were positive correlation in colon adenocarcinoma.

Conclusion:These analysis and validation results show that HSP families play an important role in the occurrence and development of various tumors and are potential tumor diagnostic and prognostic biomarkers as well as anti-cancer therapeutic targets.
Comprehensive Analysis of Aquaporin Superfamily in Lung Adenocarcinoma
Authors: Lin Guofu , Chen Luyang , Lin Lanlan , Lin Hai , Guo Zhifeng , Xu Yingxuan , Hu Chanchan , Fu Jinglan , Lin Qinhui , Chen Wenhan , Zeng Yiming , Xu Yuan
Published: October 2021

Background: Lung adenocarcinoma (LUAD) is the most predomintnt lung cancer subtype with increasing morbidity and mortality. Previous studies have shown that aquaporin (AQP) family genes were correlated with tumor progression and metastasis in several kinds of malignancies. However, their biological behaviors and prognostic values in LUAD have not been comprehensively elucidated.

Methods: RNA sequencing and real-time reverse transcription PCR (RT-PCR) were used to assess AQP1/3/4/5 gene expressions in LUAD patients using GEPIA and UALCAN databases. And then Kaplan–Meier analysis, cBioPortal, Metascape, GeneMANIA, TISIDB, and TIMER were utilized to determine the prognostic value, mutation frequency, and immune cell infiltration of AQP family members in LUAD.

Results: We found that AQP3 expression was significantly elevated and AQP1 expression was markedly reduced in LUAD patients, whereas the expression levels of AQP4 and AQP5 exhibited no significant changes. The Kaplan–Meier survival analysis indicated that the higher expressions of AQP1/4/5 were related to longer overall survival (OS). Of interest, AQP3 was significantly correlated with the clinical tumor stage and lower AQP3 expression showed favorable prognosis in stage I LUAD patients, which indicated that AQP3 may be a potential prognostic biomarker for patients. Through functional enrichment analysis, the functions of these four AQPs genes were mainly involved in the passive transport by aquaporins, water homeostasis, and protein tetramerization. Moreover, AQP1/3/4/5 expression was strongly associated with tumor-infiltrating lymphocytes (TILs) in LUAD.

Conclusion: AQP3 can be used as a prognosis and survival biomarker for stage I LUAD. These findings may provide novel insights into developing molecular targeted therapies in LUAD.
Intercepting Dementia: Awareness and Innovation as Key Tools
Authors: Brai Emanuele , Tonacci Alessandro , Brugada-Ramentol Victòria , D’Andrea Federica , Alberi Lavinia
Published: October 2021

Dementia is a common feature of several age-related brain diseases, leading to a progressive cognitive decline. Due to a growing aging rate, dementia-related disorders currently affect around 50 million people worldwide and by 2050 this number is expected to reach 150 million. Additionally to patients, these neurodegenerative pathologies have a strong impact on family members, caretakers, and other health professionals, therefore representing a public health burden that in 2020 accounted for over 1 trillion USD and is projected to nearly double in the next decade. To overcome this devastating condition, many organizations and collaborative networks sustain that only a complete understanding of dementia in its different characteristics can drive the scientific community towards the development of effective therapeutic approaches aiming at preventing its onset and halting its progression.In this work, we discuss two topics that represent fundamental resources in fighting dementia: (i) the importance of raising awareness about this condition to avoid stigma and gauging investment; and (ii) the introduction of novel screening measures to prevent and potentially revert cognitive decline. Finally, we discern how knowledge-based advocacy will help the rollout of clinical trials and the development of novel and timely pharmacological interventions.
LMT USV Toolbox, a Novel Methodological Approach to Place Mouse Ultrasonic Vocalizations in Their Behavioral Contexts—A Study in Female and Male C57BL/6J Mice and in Shank3 Mutant Females
Authors: de Chaumont Fabrice , Lemière Nathalie , Coqueran Sabrina , Bourgeron Thomas , Ey Elodie
Published: October 2021

Ultrasonic vocalizations (USVs) are used as a phenotypic marker in mouse models of neuropsychiatric disorders. Nevertheless, current methodologies still require time-consuming manual input or sound recordings clean of any background noise. We developed a method to overcome these two restraints to boost knowledge on mouse USVs. The methods are freely available and the USV analysis runs online at https://usv.pasteur.cloud. As little is currently known about usage and structure of ultrasonic vocalizations during social interactions over the long-term and in unconstrained context, we investigated mouse spontaneous communication by coupling the analysis of USVs with automatic labeling of behaviors. We continuously recorded during 3 days undisturbed interactions of same-sex pairs of C57BL/6J sexually naive males and females at 5 weeks and 3 and 7 months of age. In same-sex interactions, we observed robust differences between males and females in the amount of USVs produced, in the acoustic structure and in the contexts of emission. The context-specific acoustic variations emerged with increasing age. The emission of USVs also reflected a high level of excitement during social interactions. We finally highlighted the importance of studying long-term spontaneous communication by investigating female mice lacking Shank3, a synaptic protein associated with autism. While the previous short-time constrained investigations could not detect USV emission abnormalities, our analysis revealed robust differences in the usage and structure of the USVs emitted by mutant mice compared to wild-type female pairs.
Nucleus Reuniens Afferents in Hippocampus Modulate CA1 Network Function via Monosynaptic Excitation and Polysynaptic Inhibition
Authors: Goswamee Priyodarshan , Leggett Elizabeth , McQuiston A. Rory
Published: October 2021

The thalamic midline nucleus reuniens modulates hippocampal CA1 and subiculum function via dense projections to the stratum lacunosum-moleculare (SLM). Previously, anatomical data has shown that reuniens inputs in the SLM form synapses with dendrites of both CA1 principal cells and inhibitory interneurons. However, the ability of thalamic inputs to excite the CA1 principal cells remains controversial. In addition, nothing is known about the impact of reuniens inputs on diverse subpopulations of interneurons in CA1. Therefore, using whole cell patch-clamp electrophysiology in ex vivo hippocampal slices of wild-type and transgenic mice, we measured synaptic responses in different CA1 neuronal subtypes to optogenetic stimulation of reuniens afferents. Our data shows that reuniens inputs mediate both excitation and inhibition of the CA1 principal cells. However, the optogenetic excitation of the reuniens inputs failed to drive action potential firing in the majority of the principal cells. While the excitatory postsynaptic currents were mediated via direct monosynaptic activation of the CA1 principal cells, the inhibitory postsynaptic currents were generated polysynaptically via activation of local GABAergic interneurons. Moreover, we demonstrate that optogenetic stimulation of reuniens inputs differentially recruit at least two distinct and non-overlapping subpopulations of local GABAergic interneurons in CA1. We show that neurogliaform cells located in SLM, and calretinin-containing interneuron-selective interneurons at the SLM/stratum radiatum border can be excited by stimulation of reuniens inputs. Together, our data demonstrate that optogenetic stimulation of reuniens afferents can mediate excitation, feedforward inhibition, and disinhibition of the postsynaptic CA1 principal cells via multiple direct and indirect mechanisms.
Emerging Roles of Microglia in Neuro-vascular Unit: Implications of Microglia-Neurons Interactions
Authors: Ding Zhe , Guo Shaohui , Luo Lihui , Zheng Yueying , Gan Shuyuan , Kang Xianhui , Wu Xiaomin , Zhu Shengmei
Published: October 2021

Microglia, which serve as the defensive interface of the nervous system, are activated in many neurological diseases. Their role as immune responding cells has been extensively studied in the past few years. Recent studies have demonstrated that neuronal feedback can be shaped by the molecular signals received and sent by microglia. Altered neuronal activity or synaptic plasticity leads to the release of various communication messages from neurons, which in turn exert effects on microglia. Research on microglia-neuron communication has thus expanded from focusing only on neurons to the neurovascular unit (NVU). This approach can be used to explore the potential mechanism of neurovascular coupling across sophisticated receptor systems and signaling cascades in health and disease. However, it remains unclear how microglia-neuron communication happens in the brain. Here, we discuss the functional contribution of microglia to synapses, neuroimmune communication, and neuronal activity. Moreover, the current state of knowledge of bidirectional control mechanisms regarding interactions between neurons and microglia are reviewed, with a focus on purinergic regulatory systems including ATP-P2RY12R signaling, ATP-adenosine-A1Rs/A2ARs, and the ATP-pannexin 1 hemichannel. This review aims to organize recent studies to highlight the multifunctional roles of microglia within the neural communication network in health and disease.
The Cholinergic Lateral Line Efferent Synapse: Structural, Functional and Molecular Similarities With Those of the Cochlea
Authors: Plazas Paola V. , Elgoyhen Ana Belén
Published: October 2021

Vertebrate hair cell (HC) systems are innervated by efferent fibers that modulate their response to external stimuli. In mammals, the best studied efferent-HC synapse, the cholinergic medial olivocochlear (MOC) efferent system, makes direct synaptic contacts with HCs. The net effect of MOC activity is to hyperpolarize HCs through the activation of α9α10 nicotinic cholinergic receptors (nAChRs) and the subsequent activation of Ca2+-dependent SK2 potassium channels. A serious obstacle in research on many mammalian sensory systems in their native context is that their constituent neurons are difficult to access even in newborn animals, hampering circuit observation, mapping, or controlled manipulation. By contrast, fishes and amphibians have a superficial and accessible mechanosensory system, the lateral line (LL), which circumvents many of these problems. LL responsiveness is modulated by efferent neurons which aid to distinguish between external and self-generated stimuli. One component of the LL efferent system is cholinergic and its activation inhibits LL afferent activity, similar to what has been described for MOC efferents. The zebrafish (Danio rerio) has emerged as a powerful model system for studying human hearing and balance disorders, since LL HC are structurally and functionally analogous to cochlear HCs, but are optically and pharmacologically accessible within an intact specimen. Complementing mammalian studies, zebrafish have been used to gain significant insights into many facets of HC biology, including mechanotransduction and synaptic physiology as well as mechanisms of both hereditary and acquired HC dysfunction. With the rise of the zebrafish LL as a model in which to study auditory system function and disease, there has been an increased interest in studying its efferent system and evaluate the similarity between mammalian and piscine efferent synapses. Advances derived from studies in zebrafish include understanding the effect of the LL efferent system on HC and afferent activity, and revealing that an α9-containing nAChR, functionally coupled to SK channels, operates at the LL efferent synapse. In this review, we discuss the tools and findings of these recent investigations into zebrafish efferent-HC synapse, their commonalities with the mammalian counterpart and discuss several emerging areas for future studies.
Microglia Phenotype and Intracerebral Hemorrhage: A Balance of Yin and Yang
Authors: Bi Rentang , Fang Zhi , You Mingfeng , He Quanwei , Hu Bo
Published: October 2021

Intracerebral hemorrhage (ICH) features extremely high rates of morbidity and mortality, with no specific and effective therapy. And local inflammation caused by the over-activated immune cells seriously damages the recovery of neurological function after ICH. Fortunately, immune intervention to microglia has provided new methods and ideas for ICH treatment. Microglia, as the resident immune cells in the brain, play vital roles in both tissue damage and repair processes after ICH. The perihematomal activated microglia not only arouse acute inflammatory responses, oxidative stress, excitotoxicity, and cytotoxicity to cause neuron death, but also show another phenotype that inhibit inflammation, clear hematoma and promote tissue regeneration. The proportion of microglia phenotypes determines the progression of brain tissue damage or repair after ICH. Therefore, microglia may be a promising and imperative therapeutic target for ICH. In this review, we discuss the dual functions of microglia in the brain after an ICH from immunological perspective, elaborate on the activation mechanism of perihematomal microglia, and summarize related therapeutic drugs researches.
Functional Implications of Neurotransmitter Segregation
Authors: Cifuentes Fredy , Morales Miguel Angel
Published: October 2021

Here, we present and discuss the characteristics and properties of neurotransmitter segregation, a subtype of neurotransmitter cotransmission. We review early evidence of segregation and discuss its properties, such as plasticity, while placing special emphasis on its probable functional implications, either in the central nervous system (CNS) or the autonomic nervous system. Neurotransmitter segregation is a process by which neurons separately route transmitters to independent and distant or to neighboring neuronal processes; it is a plastic phenomenon that changes according to synaptic transmission requirements and is regulated by target-derived signals. Distant neurotransmitter segregation in the CNS has been shown to be related to an autocrine/paracrine function of some neurotransmitters. In retinal amacrine cells, segregation of acetylcholine (ACh) and GABA, and glycine and glutamate to neighboring terminals has been related to the regulation of the firing rate of direction-selective ganglion cells. In the rat superior cervical ganglion, segregation of ACh and GABA to neighboring varicosities shows a heterogeneous regional distribution, which is correlated to a similar regional distribution in transmission strength. We propose that greater segregation of ACh and GABA produces less GABAergic inhibition, strengthening ganglionic transmission. Segregation of ACh and GABA varies in different physiopathological conditions; specifically, segregation increases in acute sympathetic hyperactivity that occurs in cold stress, does not vary in chronic hyperactivity that occurs in hypertension, and rises in early ages of normotensive and hypertensive rats. Given this, we propose that variations in the extent of transmitter segregation may contribute to the alteration of neural activity that occurs in some physiopathological conditions and with age.
Effectiveness and Safety of Rituximab for Refractory Myasthenia Gravis: A Systematic Review and Single-Arm Meta-Analysis
Authors: Zhao Cong , Pu Meng , Chen Dawei , Shi Jin , Li Zhuyi , Guo Jun , Zhang Guangyun
Published: October 2021

Background and Objective: Myasthenia gravis (MG) is an autoimmune neuromuscular disease. Nearly 10–30% of patients with MG are refractory to conventional therapy. Rituximab (RTX), a monoclonal antibody targeting CD20, is increasingly used in autoimmune disorders. We performed a systematic review and meta-analysis to evaluate the effectiveness and safety of RTX for refractory MG.

Methods: Studies published between January 1, 2000 and January 17, 2021 were searched in PubMed, EMBASE, Cochrane Library, and ClincalTrails.gov. Primary outcomes included proportion of patients achieving minimal manifestation status (MMS) or better and quantitative MG (QMG) score change from baseline. Secondary outcomes were glucocorticoids (GC) doses change from baseline and proportion of patients discontinuing oral immunosuppressants.

Results: A total of 24 studies involving 417 patients were included in the meta-analysis. An overall 64% (95% confidence interval, 49–77%) of patients achieved MMS or better. The estimated reduction of QMG score was 1.55 (95% confidence interval, 0.88–2.22). The mean reduction of GC doses was 1.46 (95% confidence interval, 1.10–1.82). The proportion of patients discontinuing oral immunosuppressants was 81% (95% confidence interval, 66–93%). Subgroup analyses showed that the proportion of patients achieving MMS or better and discontinuing oral immunosuppressants was higher in MuSK-MG group than those in AChR-MG group. Improvement was more pronounced in patients with mild to moderate MG compared to those with severe MG. Moreover, the efficacy appeared to be independent of the dose of RTX. 19.6% of patients experienced adverse events, most of which were mild to moderate. Only one patient developed progressive multifocal leukoencephalopathy.

Conclusions: RTX can alleviate the symptom of weakness, decrease QMG score and reduce the doses of steroids and non-steroid immunosuppressive agents in refractory MG. It is well-tolerated with few severe adverse events. Randomized controlled trials are urgently needed to study the efficacy of RTX in treating refractory MG and to identify the characteristics of patients who might respond well to RTX.
Bioinformatics Identification of Ferroptosis-Related Biomarkers and Therapeutic Compounds in Ischemic Stroke
Authors: Chen Guozhong , Li Lin , Tao Hongmiao
Published: October 2021

Background: Stroke is one of the most common deadly diseases with an estimated 780,000 new cases globally, of which ischemic stroke accounts for over 80% of all cases. Ferroptosis is a new form of programmed cell death that plays a vital role in many diseases, including ischemic stroke and heart diseases. The role of the ferroptosis-related gene in the diagnosis, prognosis, or therapy of ischemic stroke was not fully clarified.

Methods: Ferroptosis-related differentially expressed genes (DEGs) in ischemic stroke were identified by bioinformatic analysis of the GSE16561 and GSE22255 datasets. Subsequently, receiver operator characteristic (ROC) monofactor analysis was performed to evaluate the diagnostic value of ferroptosis-related biomarkers in ischemic stroke.

Results: A total of 10 ferroptosis-related DEGs were identified in ischemic stroke vs. normal control. GO and KEGG analysis revealed that these 10 ferroptosis-related DEGs were mainly enriched in response to oxidative stress, HIF-1 signaling pathway, ferroptosis, lipid, and atherosclerosis. Moreover, the random forest model suggested three ferroptosis-related biomarkers, namely, PTGS2, MAP1LC3B, and TLR4, for ischemic stroke. Interestingly, the expression of PTGS2, MAP1LC3B, and TLR4 was upregulated in ischemic stroke. ROC monofactor analysis demonstrated a good performance of MAP1LC3B, PTGS2, and TLR4 in the diagnosis of ischemic stroke. The expression and diagnostic value of MAP1LC3B, PTGS2, and TLR4 in ischemic stroke were also verified using GSE22255. We also revealed the transcription factor regulation network and co-expressed protein network of ferroptosis-related biomarkers. Several potential therapeutic compounds corresponding to MAP1LC3B, PTGS2, and TLR4 were also identified for ischemic stroke, including Zinc12503187 (Conivaptan), Zinc3932831 (Avodart), Zinc64033452 (Lumacaftor), Zinc11679756 (Eltrombopag), Zinc100378061 (Naldemedine), and Zinc3978005 (Dihydroergotamine).

Conclusion: Our results suggested MAP1LC3B, PTGS2, and TLR4 as potential diagnostic biomarkers for ischemic stroke, providing more evidence about the vital role of ferroptosis in ischemic stroke.
Tai Chi and Yoga for Improving Balance on One Leg: A Neuroimaging and Biomechanics Study
Authors: Chen Xin-Peng , Wang Le-Jun , Chang Xiao-Qian , Wang Kuan , Wang Hui-Fang , Ni Ming , Niu Wen-Xin , Zhang Ming
Published: October 2021

The one-leg stance is frequently used in balance training and rehabilitation programs for various balance disorders. There are some typical one-leg stance postures in Tai Chi (TC) and yoga, which are normally used for improving balance. However, the mechanism is poorly understood. Besides, the differences of one-leg stance postures between TC and yoga in training balance are still unknown. Therefore, the aim of the present study was to investigate cortical activation and rambling and trembling trajectories to elucidate the possible mechanism of improving one-leg stance balance, and compare the postural demands during one-leg stance postures between TC and yoga. Thirty-two healthy young individuals were recruited to perform two TC one-leg stance postures, i.e., right heel kick (RHK) and left lower body and stand on one leg (LSOL), two yoga postures, i.e., one-leg balance and Tree, and normal one-leg standing (OLS). Brain activation in the primary motor cortex, supplementary motor area (SMA), and dorsolateral prefrontal cortex (DLPFC) was measured using functional near-infrared spectroscopy. The center of pressure was simultaneously recorded using a force platform and decomposed into rambling and trembling components. One-way repeated-measures analysis of variance was used for the main effects. The relative concentration changes of oxygenated hemoglobin (ΔHbO) in SMA were significantly higher during RHK, LSOL, and Tree than that during OLS (p < 0.001). RHK (p < 0.001), LSOL (p = 0.003), and Tree (p = 0.006) all showed significantly larger root mean square rambling (RmRMS) than that during OLS in the medial–lateral direction. The right DLPFC activation was significantly greater during the RHK than that during the Tree (p = 0.023), OLB (p < 0.001), and OLS (p = 0.013) postures. In conclusion, the RHK, LSOL, and Tree could be used as training movements for people with impaired balance. Furthermore, the RHK in TC may provide more cognitive training in postural control than Tree and OLB in yoga. Knowledge from this study could be used and implemented in training one-leg stance balance.
New Considerations for a Totally Implantable Active Middle Ear Implant
Authors: Shohet Jack , Bibee Jacqueline
Published: October 2021

Totally implantable active middle ear implants (AMEI) provide full-time hearing amplification to those with moderate to severe sensorineural hearing loss. While technology in conventional hearing aids (CHA) has advanced greatly, limitations remain for people with active lifestyles, limited vision or dexterity, and hearing aid fit issues. Furthermore, direct-drive properties of AMEI are thought to provide those with inefficient middle ear transfer functions a distinct advantage in delivering prescribed sound to the cochlea, ultimately improving speech understanding with less distortion. AMEI safety, stability, and efficacy outcomes are well documented and fitting strategies continue to improve. Recent studies show how simple aided speech testing can help predict whether a patient struggling with CHA may instead benefit from an AMEI. Totally implantable AMEI continue to be a viable option for patients who cannot or will not utilize traditional hearing aids.
A Novel Viewpoint on the Anticipatory Postural Adjustments During Gait Initiation
Authors: Farinelli Veronica , Bolzoni Francesco , Marchese Silvia Maria , Esposti Roberto , Cavallari Paolo
Published: October 2021

Anticipatory postural adjustments (APAs) are the coordinated muscular activities that precede the voluntary movements to counteract the associated postural perturbations. Many studies about gait initiation call APAs those activities that precede the heel-off of the leading foot, thus taking heel-off as the onset of voluntary movement. In particular, leg muscles drive the center of pressure (CoP) both laterally, to shift the body weight over the trailing foot and backward, to create a disequilibrium torque pushing forward the center of mass (CoM). However, since subjects want to propel their body rather than lift their foot, the onset of gait should be the CoM displacement, which starts with the backward CoP shift. If so, the leg muscles driving such a shift are the prime movers. Moreover, since the disequilibrium torque is mechanically equivalent to a forward force acting at the pelvis level, APAs should be required to link the body segments to the pelvis: distributing such concentrated force throughout the body would make all segments move homogeneously. In the aim of testing this hypothesis, we analyzed gait initiation in 15 right-footed healthy subjects, searching for activities in trunk muscles that precede the onset of the backward CoP shift. Subjects stood on a force plate for about 10 s and then started walking at their natural speed. A minimum of 10 trials were collected. A force plate measured the CoP position while wireless probes recorded the electromyographic activities. Recordings ascertained that at gait onset APAs develop in trunk muscles. On the right side, Rectus Abdominis and Obliquus Abdominis were activated in 11 and 13 subjects, respectively, starting on average 33 and 54 ms before the CoP shift; Erector Spinae (ES) at L2 and T3 levels was instead inhibited (9 and 7 subjects, 104 and 120 ms). On the contralateral side, the same muscles showed excitatory APAs (abdominals in 11 and 12 subjects, 27 and 82 ms; ES in 10 and 7 subjects, 75 and 32 ms). The results of this study provide a novel framework for distinguishing postural from voluntary actions, which may be relevant for the diagnosis and rehabilitation of gait disorders.
Cortical Visual Impairments and Learning Disabilities
Authors: Chokron Sylvie , Kovarski Klara , Dutton Gordon N.
Published: October 2021

Medical advances in neonatology have improved the survival rate of premature infants, as well as children who are born under difficult neurological conditions. As a result, the prevalence of cerebral dysfunctions, whether minimal or more severe, is increasing in all industrialized countries and in some developing nations. Whereas in the past, ophthalmological diseases were considered principally responsible for severe visual impairment, today, all recent epidemiological studies show that the primary cause of blindness and severe visual impairment in children in industrialized countries is now neurological, with lesions acquired around the time of birth currently comprising the commonest contributor. The resulting cortical or cerebral visual impairments (CVIs) have long been ignored, or have been confused either with other ophthalmological disorders causing low vision, or with a range of learning disabilities. We present here the deleterious consequences that CVI can have upon learning and social interaction, and how these can be given behavioral labels without the underlying visual causes being considered. We discuss the need to train and inform clinicians in the identification and diagnosis of CVI, and how to distinguish the diagnosis of CVI from amongst other visual disorders, including the specific learning disorders. This is important because the range of approaches needed to enhance the development of children with CVI is specific to each child’s unique visual needs, making incorrect labeling or diagnosis potentially detrimental to affected children because these needs are not met.
Selenium-Binding Protein 1 (SELENBP1) as Biomarker for Adverse Clinical Outcome After Traumatic Spinal Cord Injury
Authors: Seelig Julian , Heller Raban Arved , Haubruck Patrick , Sun Qian , Georg Klingenberg Jochen , Hackler Julian , Crowell Helena Lucia , Daniel Volker , Moghaddam Arash , Schomburg Lutz , Biglari Bahram
Published: October 2021

Graphical Abstract

The pathophysiology of traumatic spinal cord injury (TSCI) can be divided into two major phases. (A) The mechanical trauma is followed within minutes by a secondary phase consisting of local complex and intertwined acute responses, intercellular signaling and cell activity regulating pathways. Inflammatory processes, oxidative stress and hypoxia, leading to cell damage and death, and specific cell contents are released into the circulation (B). The motor and sensory deficits upon TSCI are assessed by using the American Spinal Injury Association (ASIA) impairment scale (AIS), ranging from AIS A as a complete absence of any motor and sensory functions under the lesion site, to AIS E with complete preservation of motor and sensory functions. (C) The concentrations of serum SELENBP1 were elevated in patients classified as AIS A as compared to less severely affected patients classified as AIS B, C or D. A cut-off was deduced [(SELENBP1) > 30.2 μg/L], reliably predicting whether a patient belongs to the group showing neurological recovery (G1) or not (G0) within 3 months after the trauma. The figure was created by using https://biorender.com.
Optimized-Unet: Novel Algorithm for Parapapillary Atrophy Segmentation
Authors: Wan Cheng , Wu Jiasheng , Li Han , Yan Zhipeng , Wang Chenghu , Jiang Qin , Cao Guofan , Xu Yanwu , Yang Weihua
Published: October 2021

In recent years, an increasing number of people have myopia in China, especially the younger generation. Common myopia may develop into high myopia. High myopia causes visual impairment and blindness. Parapapillary atrophy (PPA) is a typical retinal pathology related to high myopia, which is also a basic clue for diagnosing high myopia. Therefore, accurate segmentation of the PPA is essential for high myopia diagnosis and treatment. In this study, we propose an optimized Unet (OT-Unet) to solve this important task. OT-Unet uses one of the pre-trained models: Visual Geometry Group (VGG), ResNet, and Res2Net, as a backbone and is combined with edge attention, parallel partial decoder, and reverse attention modules to improve the segmentation accuracy. In general, using the pre-trained models can improve the accuracy with fewer samples. The edge attention module extracts contour information, the parallel partial decoder module combines the multi-scale features, and the reverse attention module integrates high- and low-level features. We also propose an augmented loss function to increase the weight of complex pixels to enable the network to segment more complex lesion areas. Based on a dataset containing 360 images (Including 26 pictures provided by PALM), the proposed OT-Unet achieves a high AUC (Area Under Curve) of 0.9235, indicating a significant improvement over the original Unet (0.7917).
Dysregulation of Neuronal Nicotinic Acetylcholine Receptor–Cholesterol Crosstalk in Autism Spectrum Disorder
Authors: Vallés Ana Sofía , Barrantes Francisco J.
Published: October 2021

Autism spectrum disorder (ASD) is a set of complex neurodevelopmental diseases that include impaired social interaction, delayed and disordered language, repetitive or stereotypic behavior, restricted range of interests, and altered sensory processing. The underlying causes of the core symptoms remain unclear, as are the factors that trigger their onset. Given the complexity and heterogeneity of the clinical phenotypes, a constellation of genetic, epigenetic, environmental, and immunological factors may be involved. The lack of appropriate biomarkers for the evaluation of neurodevelopmental disorders makes it difficult to assess the contribution of early alterations in neurochemical processes and neuroanatomical and neurodevelopmental factors to ASD. Abnormalities in the cholinergic system in various regions of the brain and cerebellum are observed in ASD, and recently altered cholesterol metabolism has been implicated at the initial stages of the disease. Given the multiple effects of the neutral lipid cholesterol on the paradigm rapid ligand-gated ion channel, the nicotinic acetylcholine receptor, we explore in this review the possibility that the dysregulation of nicotinic receptor-cholesterol crosstalk plays a role in some of the neurological alterations observed in ASD.
Sex Differences in Mitochondrial Function Following a Controlled Cortical Impact Traumatic Brain Injury in Rodents
Authors: Kalimon Olivia J. , Sullivan Patrick G.
Published: October 2021

Traumatic brain injury (TBI) is a complex disease to study due to the multifactorial injury cascades occurring after the initial blow to the head. One of the most vital players in this secondary injury cascade, and therapeutic target of interest, is the mitochondrion. Mitochondria are important for the generation of cellular energy, regulation of cell death, and modulation of intracellular calcium which leaves these “powerhouses” especially susceptible to damage and dysfunction following traumatic brain injury. Most of the existing studies involving mitochondrial dysfunction after TBI have been performed in male rodent models, leaving a gap in knowledge on these same outcomes in females. This mini-review intends to highlight the available data on mitochondrial dysfunction in male and female rodents after controlled cortical impact (CCI) as a common model of TBI.