bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive Equation for Angle Opening Distance at 750 μm After Laser Peripheral Iridotomy in Primary Angle Closure Suspects
Authors: Gao Xinbo , Zhou Yuying , Zuo Chengguo , Chen Liming , Ren Jiawei , Lin Huishan , Liao Yunru , Gong Haijun , Hu Huanling , Lin Mingkai
Published: August 2021

Aim: The aim of this study was to investigate the changes in anterior segment parameters as assessed by ultrasound biomicroscopy (UBM) after laser peripheral iridotomy (LPI) and to propose a prediction equation for the width of the angle after LPI.

Design: This was a prospective study.

Participants: The participants included 100 subjects with primary angle closure suspect (PACS).

Methods: Anterior segment UBM parameters were measured, whereas AOD750 was chosen to indicate the width of the angle associated with gonioscopic angle closure, as found in a prior study.

Main Outcome Measures: Angle parameters, iris parameters, anterior chamber parameters and ciliary body parameters.

Results: All angle parameters increased after LPI, including the mean angle opening distance at 750 μm (AOD750), mean angle opening distance at 500 μm from the scleral spur (AOD500), mean angle opening distance at 750 μm from the scleral spur (AOD750), and mean angle recess area at 750 μm from the scleral spur (ARA750). Among iris parameters and ciliary body parameters, the iris thickness at 2,000 μm (IT2000), iris curvature (IC), and trabecular-ciliary process distance (ICPD) were reduced after LPI. The final equation consisted of four parameters: anterior chamber depth (ACD), iris thickness at 750 μm from the scleral spur (IT750), AOD750, and lens vault (LV). This equation explained 42.7% of the variability in the angle opening indicator AOD750 after LPI, whereas in the plateau iris configuration subgroup, the accuracy of the prediction equation reached the highest a maximum of 68.6%.

Conclusions: There was an increase in angle opening and iris flattening after LPI. An equation involving four angle parameters was constructed, this equation which could explained 42.7% of the variability in the angle opening indicator AOD750 after LPI whereas in the plateau iris configuration subgroup, the accuracy of the prediction equation reached a maximum of 68.6%.
Biodiesel Production From Lignocellulosic Biomass Using Oleaginous Microbes: Prospects for Integrated Biofuel Production
Authors: Chintagunta Anjani Devi , Zuccaro Gaetano , Kumar Mahesh , Kumar S. P. Jeevan , Garlapati Vijay Kumar , Postemsky Pablo D. , Kumar N. S. Sampath , Chandel Anuj K. , Simal-Gandara Jesus
Published: August 2021

Biodiesel is an eco-friendly, renewable, and potential liquid biofuel mitigating greenhouse gas emissions. Biodiesel has been produced initially from vegetable oils, non-edible oils, and waste oils. However, these feedstocks have several disadvantages such as requirement of land and labor and remain expensive. Similarly, in reference to waste oils, the feedstock content is succinct in supply and unable to meet the demand. Recent studies demonstrated utilization of lignocellulosic substrates for biodiesel production using oleaginous microorganisms. These microbes accumulate higher lipid content under stress conditions, whose lipid composition is similar to vegetable oils. In this paper, feedstocks used for biodiesel production such as vegetable oils, non-edible oils, oleaginous microalgae, fungi, yeast, and bacteria have been illustrated. Thereafter, steps enumerated in biodiesel production from lignocellulosic substrates through pretreatment, saccharification and oleaginous microbe-mediated fermentation, lipid extraction, transesterification, and purification of biodiesel are discussed. Besides, the importance of metabolic engineering in ensuring biofuels and biorefinery and a brief note on integration of liquid biofuels have been included that have significant importance in terms of circular economy aspects.
An Auto-Regulating Type II Toxin-Antitoxin System Modulates Drug Resistance and Virulence in Streptococcus suis
Authors: Gu Qibing , He Peijuan , Wang Dan , Ma Jiale , Zhong Xiaojun , Zhu Yinchu , Zhang Yue , Bai Qiankun , Pan Zihao , Yao Huochun
Published: August 2021

Toxin-antitoxin (TA) systems are ubiquitous genetic elements that play an essential role in multidrug tolerance and virulence of bacteria. So far, little is known about the TA systems in Streptococcus suis. In this study, the Xress-MNTss TA system, composed of the MNTss toxin in the periplasmic space and its interacting Xress antitoxin, was identified in S. suis. β-galactosidase activity and electrophoretic mobility shift assay (EMSA) revealed that Xress and the Xress-MNTss complex could bind directly to the Xress-MNTss promoter as well as downregulate streptomycin adenylyltransferase ZY05719_RS04610. Interestingly, the Xress deletion mutant was less pathogenic in vivo following a challenge in mice. Transmission electron microscopy and adhesion assays pointed to a significantly thinner capsule but greater biofilm-formation capacity in ΔXress than in the wild-type strain. These results indicate that Xress-MNTss, a new type II TA system, plays an important role in antibiotic resistance and pathogenicity in S. suis.
Multi-Omic Analysis of Symbiotic Bacteria Associated With Aedes aegypti Breeding Sites
Authors: Mosquera Katherine D. , Martinez Villegas Luis E. , Pidot Sacha J. , Sharif Chinhda , Klimpel Sven , Stinear Timothy P. , Moreira Luciano A. , Tobias Nicholas J. , Lorenzo Marcelo G.
Published: August 2021

Mosquito breeding sites are complex aquatic environments with wide microbial diversity and physicochemical parameters that can change over time during the development of immature insect stages. Changes in biotic and abiotic conditions in water can alter life-history traits of adult mosquitos but this area remains understudied. Here, using microbial genomic and metabolomics analyses, we explored the metabolites associated with Aedes aegypti breeding sites as well as the potential contribution of Klebsiella sp., symbiotic bacteria highly associated with mosquitoes. We sought to address whether breeding sites have a signature metabolic profile and understand the metabolite contribution of the bacteria in the aquatic niches where Ae. aegypti larvae develop. An analysis of 32 mosquito-associated bacterial genomes, including Klebsiella, allowed us to identify gene clusters involved in primary metabolic pathways. From them, we inferred metabolites that could impact larval development (e.g., spermidine), as well as influence the quality assessment of a breeding site by a gravid female (e.g., putrescine), if produced by bacteria in the water. We also detected significant variance in metabolite presence profiles between water samples representing a decoupled oviposition event (oviposition by single females and manually deposited eggs) versus a control where no mosquito interactions occurred (PERMANOVA: p < 0.05; R2 = 24.64% and R2 = 30.07%). Five Klebsiella metabolites were exclusively linked to water samples where oviposition and development occurred. These data suggest metabolomics can be applied to identify compounds potentially used by female Ae. aegypti to evaluate the quality of a breeding site. Elucidating the physiological mechanisms by which the females could integrate these sensory cues while ovipositing constitutes a growing field of interest, which could benefit from a more depurated list of candidate molecules.
Integrated Bacterial and Fungal Diversity Analysis Reveals the Gut Microbial Alterations in Diarrheic Giraffes
Authors: Li Aoyun , Liu Bingxian , Li Feiran , He Yuanyuan , Wang Lei , Fakhar-e-Alam Kulyar Muhammad , Li Huade , Fu Yuhang , Zhu Huaisen , Wang Yaping , Jiang Xiong
Published: August 2021

Gut microbiota has been demonstrated to be associated with multiple gastrointestinal diseases, but information regarding the gut microbial alternations in diarrheic giraffe remains scarce. Here, 16S rDNA and ITS gene amplicon sequencing were conducted to investigate the gut microbial composition and variability in diarrheic giraffes. Results demonstrated that Firmicutes and Proteobacteria were the most dominant phyla in the gut bacterial community, whereas Ascomycota and Basidiomycota were observed to be predominant in the gut fungal community regardless of health status. However, the species and relative abundance of preponderant bacterial and fungal genera in healthy and diarrheic giraffes were different. In contrast to the relatively stabilized gut fungal community, gut bacterial community displayed a significant decrease in the alpha diversity, accompanied by distinct changes in taxonomic compositions. Bacterial taxonomic analysis revealed that the relative abundances of eight phyla and 12 genera obviously increased, whereas the relative abundances of two phyla and eight genera dramatically decreased during diarrhea. Moreover, the relative richness of five fungal genera significantly increased, whereas the relative richness of seven fungal genera significantly declined in diarrheic giraffes. Taken together, this study demonstrated that diarrhea could cause significant alternations in the gut microbial composition of giraffes, and the changes in the gut bacterial community were more significant than those in the gut fungal community. Additionally, investigating the gut microbial characteristics of giraffes in different health states is beneficial to provide a theoretical basis for establishing a prevention and treatment system for diarrhea from the gut microbial perspective.
Synbiotics Containing Nanoprebiotics: A Novel Therapeutic Strategy to Restore Gut Dysbiosis
Authors: Hong Liang , Lee Sang-Mok , Kim Whee-Soo , Choi Yun-Jaie , Oh Seo-Ho , Li Yu-Ling , Choi Seung-Hoon , Chung Dong Hyen , Jung Eunkyoung , Kang Sang-Kee , Cho Chong-Su
Published: August 2021

A new formulation, nanoprebiotics [e.g., phthalyl pullulan nanoparticles (PPNs)], was demonstrated to enhance the antimicrobial activity of probiotics [e.g., Lactobacillus plantarum (LP)] in vitro through intracellular stimulation better than that by backbone prebiotics, which are commonly used. In this study, we aimed to investigate whether this combination would exert distinct effects as synbiotics in vivo. Synbiotics combinations of LP, pullulan, and PPNs were used as experimental treatments in a dysbiosis-induced murine model, and their restorative effect was assessed using pathogen Escherichia coli K99 challenge. Our results showed that the E. coli infection was suppressed markedly in the experimental group fed with synbiotics containing PPNs. In addition, the decrease in serum endotoxin level after synbiotics treatment suggested the reinforcement of the gut barrier. Comparison of treatment groups, including a normal control group, showed that synbiotics containing PPNs increased microbial diversity, which is a representative parameter of healthy status. Furthermore, distinct from probiotics treatment alone, synbiotics showed additive effects of enrichment of several well-known beneficial bacteria such as Lactobacillus, Bifidobacterium, and other butyrate-producing bacteria including Faecalibacterium. Collectively, our results indicate that synbiotics containing PPNs are effective at restoring gut dysbiosis, suppressing pathogenic infection, and increasing microbial diversity, suggesting that synbiotics with nanoprebiotics have the potential to be a novel strategy for ameliorating gut dysbiosis and infectious diseases.
An Integrative Approach to Determine 3D Protein Structures Using Sparse Paramagnetic NMR Data and Physical Modeling
Authors: Gaalswyk Kari , Liu Zhihong , Vogel Hans J. , MacCallum Justin L.
Published: August 2021

Paramagnetic nuclear magnetic resonance (NMR) methods have emerged as powerful tools for structure determination of large, sparsely protonated proteins. However traditional applications face several challenges, including a need for large datasets to offset the sparsity of restraints, the difficulty in accounting for the conformational heterogeneity of the spin-label, and noisy experimental data. Here we propose an integrative approach to structure determination combining sparse paramagnetic NMR with physical modelling to infer approximate protein structural ensembles. We use calmodulin in complex with the smooth muscle myosin light chain kinase peptide as a model system. Despite acquiring data from samples labeled only at the backbone amide positions, we are able to produce an ensemble with an average RMSD of ∼2.8 Å from a reference X-ray crystal structure. Our approach requires only backbone chemical shifts and measurements of the paramagnetic relaxation enhancement and residual dipolar couplings that can be obtained from sparsely labeled samples.
Genetic Analysis and Literature Review of SNCA Variants in Parkinson's Disease
Authors: Guo Yi , Sun Yan , Song Zhi , Zheng Wen , Xiong Wei , Yang Yan , Yuan Lamei , Deng Hao
Published: August 2021

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder. Aging, environmental factors, and genetics are considered as risk factors. The alpha-synuclein gene (SNCA), the first pathogenic gene identified in a familial form of PD, was indisputably involved as a heritable component for familial and sporadic PD. In this study, whole-exome sequencing and Sanger sequencing were performed to evaluate the association between the SNCA gene variants and PD. The genetic data of 438 clinically diagnosed patients with PD and 543 matched control populations of the Han Chinese were analyzed. The literature review of SNCA variants for 231 cases reported in 89 articles was extracted from the PubMed and the Movement Disorder Society Genetic mutation database. No potentially causative variant(s) in the SNCA gene, excepting two single-nucleotide nonsynonymous variants c.158C>T (p.A53V, rs542171324) and c.349C>T (p.P117S, rs145138372), were detected. There was no statistically significant difference in the genotypic or allelic frequencies for either variant between the PD group and the control group (all P > 0.05). No copy number variants of the SNCA gene were detected. The results of this study suggest that the variants in the exons of the SNCA gene may have less or no role in the development of PD in the Han Chinese populations. The literature review suggests that psychiatric signs and cognitive decline/dementia were more common among patients with SNCA duplication or triplication (psychiatric signs: χ2 = 7.892, P = 0.005; cognitive decline/dementia: χ2 = 8.991, P = 0.003).
Increased Endogenous GDNF in Mice Protects Against Age-Related Decline in Neuronal Cholinergic Markers
Authors: Mitra Sumonto , Turconi Giorgio , Darreh-Shori Taher , Mätlik Kärt , Aquilino Matilde , Eriksdotter Maria , Andressoo Jaan-Olle
Published: August 2021

Gradual decline in cholinergic transmission and cognitive function occurs during normal aging, whereas pathological loss of cholinergic function is a hallmark of different types of dementia, including Alzheimer’s disease (AD), Lewy body dementia (LBD), and Parkinson’s disease dementia (PDD). Glial cell line-derived neurotrophic factor (GDNF) is known to modulate and enhance the dopamine system. However, how endogenous GDNF influences brain cholinergic transmission has remained elusive. In this study, we explored the effect of a twofold increase in endogenous GDNF (Gdnf hypermorphic mice, Gdnfwt/hyper) on cholinergic markers and cognitive function upon aging. We found that Gdnfwt/hyper mice resisted an overall age-associated decline in the cholinergic index observed in the brain of Gdnfwt/wt animals. Biochemical analysis revealed that the level of nerve growth factor (NGF), which is important for survival and function of central cholinergic neurons, was significantly increased in several brain areas of old Gdnfwt/hyper mice. Analysis of expression of genes involved in cholinergic transmission in the cortex and striatum confirmed modulation of cholinergic pathways by GDNF upon aging. In line with these findings, Gdnfwt/hyper mice did not undergo an age-related decline in cognitive function in the Y-maze test, as observed in the wild type littermates. Our results identify endogenous GDNF as a potential modulator of cholinergic transmission and call for future studies on endogenous GDNF function in neurodegenerative disorders characterized by cognitive impairments, including AD, LBD, and PDD.
Gaussian Process Based Model Predictive Control for Overtaking in Autonomous Driving
Authors: Liu Wenjun , Liu Chang , Chen Guang , Knoll Alois
Published: August 2021

This paper proposes a novel framework for addressing the challenge of autonomous overtaking and obstacle avoidance, which incorporates the overtaking path planning into Gaussian Process-based model predictive control (GPMPC). Compared with conventional control strategies, this approach has two main advantages. Firstly, combining Gaussian Process (GP) regression with a nominal model allows for learning from model mismatch and unmodeled dynamics, which enhances a simple model and delivers significantly better results. Due to the approximation for propagating uncertainties, we can furthermore satisfy the constraints and thereby the safety of the vehicle is ensured. Secondly, we convert the geometric relationship between the ego vehicle and other obstacle vehicles into the constraints. Without relying on a higher-level path planner, this approach substantially reduces the computational burden. In addition, we transform the state constraints under the model predictive control (MPC) framework into a soft constraint and incorporate it as relaxed barrier function into the cost function, which makes the optimizer more efficient. Simulation results indicate that the proposed method can not only fulfill the overtaking tasks but also maintain safety at all times.
Structural and Lipidomic Alterations of Striatal Myelin in 16p11.2 Deletion Mouse Model of Autism Spectrum Disorder
Authors: Ju Jun , Yang Xiuyan , Jiang Jian , Wang Dilong , Zhang Yumeng , Zhao Xiaofeng , Fang Xiaoyi , Liao Huanquan , Zheng Lei , Li Shupeng , Hou Sheng-Tao , Liang Liyang , Pan Yihang , Li Huiliang , Li Ningning
Published: August 2021

Myelin abnormalities have been observed in autism spectrum disorder (ASD). In this study, we seek to discover myelin-related changes in the striatum, a key brain region responsible for core ASD features, using the 16p11.2 deletion (16p11.2±) mouse model of ASD. We found downregulated expression of multiple myelin genes and decreased myelin thickness in the striatum of 16p11.2±mice versus wild type controls. Moreover, given that myelin is the main reservoir of brain lipids and that increasing evidence has linked dysregulation of lipid metabolism to ASD, we performed lipidomic analysis and discovered decreased levels of certain species of sphingomyelin, hexosyl ceramide and their common precursor, ceramide, in 16p11.2±striatum, all of which are major myelin components. We further identified lack of ceramide synthase 2 as the possible reason behind the decrease in these lipid species. Taken together, our data suggest a role for myelin and myelin lipids in ASD development.
Olfactory Deficits in the Freezing of Gait Phenotype of Parkinson's Disease
Authors: Glover Aliyah , Pillai Lakshmi , Dhall Rohit , Virmani Tuhin
Published: August 2021

Background: Olfactory dysfunction often occurs before motor onset in Parkinson's disease (PD) and can be detected with the University of Pennsylvania Smell Identification Test (UPSIT). Based on the Braak hypothesis, the olfactory bulb is one of two sites where disease pathology may start and spread to deeper brain structures.

Objective: To evaluate whether a specific pattern of odorant identification on the UPSIT discriminated Parkinson's disease patients with and without freezing of gait.

Methods: One hundred and twenty four consecutive participants (33 controls, 31 non-freezers, and 60 freezers) were administered the UPSIT. Using the chi-square test, each odorant on the UPSIT was ranked based on the differential ability of freezers and non-freezers to identify them correctly. Using predictive statistics and confusion matrices, the best combination of odorants and a cut-off score was determined.

Results: Freezers had a shift toward a more severe hyposmia classification based on age and sex based normative values. The correct identification of nine odors (bubblegum, chocolate, smoke, wintergreen, paint thinner, orange, strawberry, grass, and peanut) was significantly worse in freezers compared to non-freezers. Correctly identifying ≤ 2 out of 3-odorants (bubblegum, chocolate, and smoke) had a 77% sensitivity and 61% specificity for categorizing freezers. The 3-odorant score was not correlated with disease duration, motor or total UPDRS scores, MoCA scores or age at testing. The predictive statistics were similar when sexes were separately categorized.

Conclusions: A 3-odorant score helped categorize freezers and non-freezers with similar sensitivity and specificity to short odorant Parkinson's disease identification batteries.
The SEEKING Drive and Its Fixation: A Neuro-Psycho-Evolutionary Approach to the Pathology of Addiction
Authors: Alcaro Antonio , Brennan Anthony , Conversi David
Published: August 2021

Neuro-ethological studies conducted by Panksepp and his colleagues have provided an understanding of how the activity of the mesolimbic dopaminergic (ML DA) system leads to the emotional disposition to SEEK/Explore, which is involved in all appetitive motivated behavior and mental activity. In pathological addiction phenomena, this emotional disposition “fixes” itself on certain obsessive-compulsive habits, losing its versatility and its natural predisposition to spontaneous and unconditioned activation. Overall, the result is a consistent disinterest in everything that is not the object of addiction. From a neuro-psycho-evolutionary point of view, the predisposition to develop addictive behavior can be attributed to a loss of “functional autonomy” of the SEEKING/Explorative disposition. Indeed, as shown by animal and human studies, the tendency to be conditioned by situations and contexts that provide an immediate reward can be closely related to a deficit in the tonic endogenous activity of the ML DA-SEEKING system.
Intensity-Dependent Changes in Quantified Resting Cerebral Perfusion With Multiple Sessions of Transcranial DC Stimulation
Authors: Sherwood Matthew S. , McIntire Lindsey , Madaris Aaron T. , Kim Kamin , Ranganath Charan , McKinley R. Andy
Published: August 2021

Transcranial direct current stimulation (tDCS) to the left prefrontal cortex has been shown to produce broad behavioral effects including enhanced learning and vigilance. Still, the neural mechanisms underlying such effects are not fully understood. Furthermore, the neural underpinnings of repeated stimulation remain understudied. In this work, we evaluated the effects of the repetition and intensity of tDCS on cerebral perfusion [cerebral blood flow (CBF)]. A cohort of 47 subjects was randomly assigned to one of the three groups. tDCS of 1- or 2-mA was applied to the left prefrontal cortex on three consecutive days, and resting CBF was quantified before and after stimulation using the arterial spin labeling MRI and then compared with a group that received sham stimulation. A widespread decreased CBF was found in a group receiving sham stimulation across the three post-stimulation measures when compared with baseline. In contrast, only slight decreases were observed in the group receiving 2-mA stimulation in the second and third post-stimulation measurements, but more prominent increased CBF was observed across several brain regions including the locus coeruleus (LC). The LC is an integral region in the production of norepinephrine and the noradrenergic system, and an increased norepinephrine/noradrenergic activity could explain the various behavioral findings from the anodal prefrontal tDCS. A decreased CBF was observed in the 1-mA group across the first two post-stimulation measurements, similar to the sham group. This decreased CBF was apparent in only a few small clusters in the third post-stimulation scan but was accompanied by an increased CBF, indicating that the neural effects of stimulation may persist for at least 24 h and that the repeated stimulation may produce cumulative effects.
Access to Procedural Memories After One Year: Evidence for Robust Memory Consolidation in Tourette Syndrome
Authors: Tóth-Fáber Eszter , Tárnok Zsanett , Takács Ádám , Janacsek Karolina , Németh Dezső
Published: August 2021

Tourette syndrome is a childhood-onset neurodevelopmental disorder characterized by motor and vocal tics. On the neural level, tics are thought to be related to the disturbances of the cortico-basal ganglia-thalamo-cortical loops, which also play an important role in procedural learning. Several studies have investigated the acquisition of procedural information and the access to established procedural information in TS. Based on these, the notion of procedural hyperfunctioning, i.e., enhanced procedural learning, has been proposed. However, one neglected area is the retention of acquired procedural information, especially following a long-term offline period. Here, we investigated the 5-hour and 1-year consolidation of two aspects of procedural memory, namely serial-order and probability-based information. Nineteen children with TS between the ages of 10 and 15 as well as 19 typically developing gender- and age-matched controls were tested on a visuomotor four-choice reaction time task that enables the simultaneous assessment of the two aspects. They were retested on the same task 5 hours and 1 year later without any practice in the offline periods. Both groups successfully acquired and retained the probability-based information both when tested 5 hours and then 1 year later, with comparable performance between the TS and control groups. Children with TS did not acquire the serial-order information during the learning phase; hence, retention could not be reliably tested. Our study showed evidence for short-term and long-term retention of one aspect of procedural memory, namely probability-based information in TS, whereas learning of serial-order information might be impaired in this disorder.
Serotonergic Modulation of Nigrostriatal and Mesolimbic Dopamine and Motor/Exploratory Behaviors in the Rat
Authors: Nikolaus Susanne , Wittsack Hans-Jörg , Antke Christina , Beu Markus , Hautzel Hubertus , Decheva Cvetana , Mamlins Eduards , Mori Yuriko , Huston Joseph P. , Antoch Gerald , Müller Hans-Wilhelm
Published: August 2021

Purpose:The 5-HT2Areceptor (R) is known to modulate dopamine (DA) release in the mammalian brain. Altanserin (ALT) and 2,5-dimethoxy-4-iodoamphetamine (DOI) act as 5-HT2AR antagonist and agonist, respectively. In the present study, we assessed the effects of ALT and DOI on motor and exploratory behaviors and on D2/3R binding in the rat brain within vivoimaging methods.

Methods:D2/3R binding was determined after systemic application of ALT (10 mg/kg) or DOI (0.5 mg/kg) and the respective vehicles [dimethyl sulfoxide (DMSO) and 0.9% saline (SAL)] with [123I]IBZM as a single-photon emission computed tomography (SPECT) radioligand. Anatomical information for the delineation of the target regions was obtained with dedicated small animal MRI. Immediately after 5-HT2AR antagonistic or agonistic treatment, motor/exploratory behaviors were assessed for 45 (ALT) or 30 min (DOI) in an open field. Additional rats underwent behavioral measurements after injection of DMSO or SAL.

Results:ALT increased D2/3R binding in the ventral hippocampus relative to vehicle, while DOI augmented D2/3R binding in caudate putamen, frontal cortex, motor cortex, and ventral hippocampus. The 5-HT2AR agonist as well as antagonist decreased parameters of motor activity and active exploration. However, ALT, in contrast to DOI, decreased explorative head–shoulder motility and increased sitting.

Conclusions:The regional increases of D2/3R binding after ALT and DOI (90 and 75 min post-challenge) may be conceived to reflect decreases of synaptic DA. The reductions of motor/exploratory activities (min 1–45 and min 1–30 after challenge with ALT and DOI, respectively) contrast the regional reductions of D2/3R binding, as they indicate elevated DA levels at the time of behavioral measurements. It may be concluded that ALT and DOI modulate DA in the individual regions of the nigrostriatal and mesolimbocortical pathways differentially and in a time-dependent fashion.
An Empirical Comparative Study on the Two Methods of Eliciting Singers’ Emotions in Singing: Self-Imagination and VR Training
Authors: Zhang Jin , Xu Ziming , Zhou Yueying , Wang Pengpai , Fu Ping , Xu Xijia , Zhang Daoqiang
Published: August 2021

Emotional singing can affect vocal performance and the audience’s engagement. Chinese universities use traditional training techniques for teaching theoretical and applied knowledge. Self-imagination is the predominant training method for emotional singing. Recently, virtual reality (VR) technologies have been applied in several fields for training purposes. In this empirical comparative study, a VR training task was implemented to elicit emotions from singers and further assist them with improving their emotional singing performance. The VR training method was compared against the traditional self-imagination method. By conducting a two-stage experiment, the two methods were compared in terms of emotions’ elicitation and emotional singing performance. In the first stage, electroencephalographic (EEG) data were collected from the subjects. In the second stage, self-rating reports and third-party teachers’ evaluations were collected. The EEG data were analyzed by adopting the max-relevance and min-redundancy algorithm for feature selection and the support vector machine (SVM) for emotion recognition. Based on the results of EEG emotion classification and subjective scale, VR can better elicit the positive, neutral, and negative emotional states from the singers than not using this technology (i.e., self-imagination). Furthermore, due to the improvement of emotional activation, VR brings the improvement of singing performance. The VR hence appears to be an effective approach that may improve and complement the available vocal music teaching methods.
Bilateral Intracranial Beta Activity During Forced and Spontaneous Movements in a 6-OHDA Hemi-PD Rat Model
Authors: Mottaghi Soheil , Kohl Sandra , Biemann Dirk , Liebana Samuel , Montaño Crespo Ruth Eneida , Buchholz Oliver , Wilson Mareike , Klaus Carolin , Uchenik Michelle , Münkel Christian , Schmidt Robert , Hofmann Ulrich G.
Published: August 2021

Cortico-basal ganglia beta oscillations (13–30 Hz) are assumed to be involved in motor impairments in Parkinson’s Disease (PD), especially in bradykinesia and rigidity. Various studies have utilized the unilateral 6-hydroxydopamine (6-OHDA) rat PD model to further investigate PD and test novel treatments. However, a detailed behavioral and electrophysiological characterization of the model, including analyses of popular PD treatments such as DBS, has not been documented in the literature. We hence challenged the 6-OHDA rat hemi-PD model with a series of experiments (i.e., cylinder test, open field test, and rotarod test) aimed at assessing the motor impairments, analyzing the effects of Deep Brain Stimulation (DBS), and identifying under which conditions excessive beta oscillations occur. We found that 6-OHDA hemi-PD rats presented an impaired performance in all experiments compared to the sham group, and DBS could improve their overall performance. Across all the experiments and behaviors, the power in the high beta band was observed to be an important biomarker for PD as it showed differences between healthy and lesioned hemispheres and between 6-OHDA-lesioned and sham rats. This all shows that the 6-OHDA hemi-PD model accurately represents many of the motor and electrophysiological symptoms of PD and makes it a useful tool for the pre-clinical testing of new treatments when low β (13–21 Hz) and high β (21–30 Hz) frequency bands are considered separately.
Detecting Abnormal Neuronal Activity in a Chronic Migraine Model by Egr1-EGFP Transgenic Mice
Authors: Wang Fei , Jiang Weiqing , Gao Li , Liu Chen , Deng Mingzhu , Ren Xiao , Zhu Chenlu , Guan Ji-Song , Wang Yonggang
Published: August 2021

Chronic migraine (CM) is a highly disabling neurological disorder characterized by recurrent headache accompanied by a variety of sensory and/or emotional symptoms. However, the mechanisms of migraine onset and its chronicity have not been elucidated. The present study was designed to search for brain regions and neurons that were abnormally activated by CM and might be related to its pathogenesis and different concomitant symptoms. CM models were established here by repeated intraperitoneal injection of nitroglycerin (NTG) every other day for 9 days to early growth response gene 1 (Egr1)-enhanced green fluorescent protein (EGFP) transgenic mice, which allowed monitoring of neuronal activities in the whole brain. CM-related behaviors were recorded through head grooming test and light aversion assay. Elevation of Egr1 expression signals was detected in trigeminal nucleus caudalis (TNC), primary somatosensory cortex (SSp), lateral amygdala nucleus (LA), primary visual area (VISp), and temporal association areas (TEa) 2 h after the last injection of NTG by immunofluorescence and digital slice scanning technology. Meanwhile, no change of Egr1 expression was found in auditory areas (AUD), CA1, ectorhinal area (ECT), piriform (PIR), and anterior cingulate area (ACC). Furthermore, with the strongest support by evidence-based medicine among the current limited oral treatments of CM, topiramate was administrated every day for 11 days from 2 days before the first NTG injection. The results showed that topiramate partially improved the photophobia behavior of CM models in the short-term with gradually weakened efficacy as the course of the disease prolonged. Meanwhile, NTG-induced increase in Egr1 expression was completely reversed in TNC, SSp, and VISp and partially reduced in LA and TEa by topiramate at the same time point mentioned above. In conclusion, the current results suggested that the abnormal hyperactivities in TNC, SSp and VISp were associated with the pathogenesis of CM.
Vitamin D Deficiency in Children With Vasovagal Syncope Is Associated With Impaired Circadian Rhythm of Blood Pressure
Authors: Zou Runmei , Wang Shuo , Cai Hong , Li Fang , Lin Ping , Wang Yuwen , Wang Cheng
Published: August 2021

Background

Vitamin D deficiency is associated with the risk of cardiovascular diseases. We aimed to investigate the serum vitamin D levels in children with vasovagal syncope (VVS) and explore the correlation of vitamin D status and circadian rhythm of blood pressure in VVS pediatric patients.

Methods

This was a retrospective study. 130 syncopal children diagnosed with VVS were included in the study. 110 age and gender matched healthy individuals were enrolled as control. According to serum 25(OH)D levels, VVS patients were divided into vitamin D sufficient group and vitamin D deficient group. Detailed information of VVS children with vitamin D deficiency and sufficiency on demographic data, baseline laboratory testing, echocardiogram, ambulatory blood pressure monitoring, and Holter ECG recording were extracted and analyzed.

Results

VVS children had a higher prevalence of vitamin D deficiency compared with healthy individuals (33.8% vs. 20.0%, P = 0.017). VVS patients with vitamin D deficiency had a higher rate of non-dipper blood pressure (79.5% vs. 59.3%, P = 0.021) and a lower value of square root of mean squared differences of successive normal to normal intervals (rMSSD) (median 107.8 vs. 141.0 ms, P = 0.035) compared with those with vitamin D sufficiency. Logistic regression analysis showed that non-dipper blood pressure was associated with serum 25(OH)D level [OR = 0.979, 95% CI (0.960, 0.999), P = 0.036].

Conclusion

VVS pediatric patients had a higher prevalence of vitamin D deficiency. VVS children with vitamin D deficiency showed a higher rate of non-dipper blood pressure, suggesting that vitamin D deficiency is correlated with impaired circadian rhythm of blood pressure.
Genome-Wide Meta-Analysis Identifies Two Novel Risk Loci for Epilepsy
Authors: Song Meng , Liu Jiewei , Yang Yongfeng , Lv Luxian , Li Wenqiang , Luo Xiong-Jian
Published: August 2021

Epilepsy (affects about 70 million people worldwide) is one of the most prevalent brain disorders and imposes a huge economic burden on society. Epilepsy has a strong genetic component. In this study, we perform the largest genome-wide meta-analysis of epilepsy (N = 8,00,869 subjects) by integrating four large-scale genome-wide association studies (GWASs) of epilepsy. We identified three genome-wide significant (GWS) (p < 5 × 10–8) risk loci for epilepsy. The risk loci on 7q21.11 [lead single nucleotide polymorphism (SNP) rs11978015, p = 9.26 × 10–9] and 8p23.1 (lead SNP rs28634186, p = 4.39 × 10–8) are newly identified in the present study. Of note, rs11978015 resides in upstream of GRM3, which encodes glutamate metabotropic receptor 3. GRM3 has pivotal roles in neurotransmission and is involved in most aspects of normal brain function. In addition, we also identified three genes (TTC21B, RP11-375N15.2, and TNKS) whose cis-regulated expression level are associated with epilepsy, indicating that risk variants may confer epilepsy risk through regulating the expression of these genes. Our study not only provides new insights into genetic architecture of epilepsy but also prioritizes potential molecular targets (including GRM3 and TTC21B) for development of new drugs and therapeutics for epilepsy.
Comparative Proteomics of Human Milk From Eight Cities in China During Six Months of Lactation in the Chinese Human Milk Project Study
Authors: Sari Ratna Nurmalita , Pan Jiancun , Zhang Wenyuan , Li Yuanyuan , Zhu Huiquan , Pang Xiaoyang , Zhang Shuwen , Jiang Shilong , Lu Jing , Lv Jiaping
Published: August 2021

Human milk (HM) is the golden standard of infant nutrition that can protect immature body function and enhance nutrition metabolism to ensure infant growth. Region specificity and lactation period could change the protein composition in HM. In this research, proteomics analysis was used to compare proteomes across eight cities, namely Harbin, Lanzhou, Guangzhou, Chengdu, Jinhua, Weihai, Zhengzhou, and Beijing, which represented the northeast, northwest, southeast, southwest, east, and north and central regions of China,. Proteins varied significantly among the cities. These different proteins were mainly involved in the process of platelet degranulation, innate immune response, and triglyceride metabolic process, which might be due to different living environments. These differences also lead to variation in protection and fat metabolism from mothers to infants in different cities. Four proteins were expressed differently during 6 months of lactation, namely Dipeptidyl peptidase 1, Lysozyme C, Carbonic anhydrase 6, and Chordin-like protein 2. The changes in these proteins might be because of the change of growth needs of the infants. The findings from our results might help to improve the understanding of HM as well as to design infant formula.
Inhibition Effect of Extract of Psychotria viridiflora Stem on α-Amylase and α-Glucosidase and Its Application in Lowering the Digestibility of Noodles
Authors: Chen Qimin , Toy Joanne Yi Hui , Seta Cynthia , Yeo Tiong Chia , Huang Dejian
Published: August 2021

A collection of tropical medicinal plants from East Malaysia's rainforests are used by indigenous tribes for their curative properties. Despite their purported healing properties, these forest plant species are largely unexplored and hence remain virtually unknown to the outside world. In this study, antidiabetic properties of Psychotria viridiflora, a plant used to treat diabetes by a local community in Sarawak, Malaysia were investigated. Ethyl acetate (EA) extract of P. viridiflora stem was found to exhibit high starch hydrolase inhibition activity with an IC50 value of 15.4 ± 2.1 μg/ml against porcine α-amylase and an IC50 value of 32.4 ± 3.7 μg/ml against rat intestinal α-glucosidase. A complex mixture of A-type oligomeric proanthocyanidins containing (epi)fisetinidol, (epi)afzelechin, (epi)guibourtinidol, and (epi)catechin were found. These compounds may be responsible for the starch hydrolase inhibition activity. Ethyl acetate (EA) extract of P. viridiflora stem was incorporated into wheat and rice flour to reformulate noodles with slow digestibility and was assessed under in vitro simulated gastrointestinal conditions. A dose-dependent effect on digestibility was observed for both noodles upon incorporation of 1-6% (w/w) of EA extract, with noodles containing 6% (w/w) extract exhibiting the greatest reduction in digestibility. As compared to rice noodles containing 6% extract (31.16% inhibition), wheat noodles with the same extract concentration had a smaller decline in digestibility (27.25% inhibition) after 180 min. Overall, our findings highlight the potential of P. viridiflora in the prevention of postprandial hyperglycaemia.
Kampo Medicine Treatment for Advanced Pancreatic Cancer: A Case Series
Authors: Shimizu Masayuki , Takayama Shin , Kikuchi Akiko , Arita Ryutaro , Ono Rie , Ishizawa Kota , Ishii Tadashi
Published: August 2021

Aims: The present report aims to investigate the use of Kampo medicine for advanced pancreatic cancer patients in order to prolong survival.

Methods: We retrospectively reviewed medical records of patients with pancreatic cancer who presented to our Shimizu Clinic from 2000 to 2020. Patients who survived at least twice as long as the initial prognostic estimate were selected and their treatment was reviewed. The Kampo formula and crude drugs were selected according to the Kampo diagnosis and treatment strategy, which included qi and blood supplementation; qi, blood and water smoothing; and inflammation (termed “heat”) and cancer suppression.

Results: Ten patients aged 45–80 years (six males and four females) with stage IV advanced cancer were selected. All patients received hozai, which is a tonic formula, of juzentaihoto (JTT) or hochuekkito (HET) decoction. Anti-cancer crude drugs were included in the decoctions of nine patients. At the first visit, the estimated life expectancy for all patients was no more than 1 year; however, treatment with Western and Kampo medicine led to a relatively long survival period of over 2 years. Three patients were still living at the time of this writing, more than 2, 6, and 14 years after treatment initiation.

Conclusion: Our results suggest that Kampo medicine may be useful for disease control and supportive care for patients with advanced pancreatic cancer.
The Role of Immunobiotics and Postbiotics in the Recovery of Immune Cell Populations From Respiratory Mucosa of Malnourished Hosts: Effect on the Resistance Against Respiratory Infections
Authors: Salva Susana , Kolling Yanina , Ivir Maximiliano , Gutiérrez Florencia , Alvarez Susana
Published: August 2021

Malnutrition is associated with a state of secondary immunodeficiency, which is characterized by a worsening of the immune response against infectious agents. Despite important advances in vaccines and antibiotic therapies, the respiratory infections are among the leading causes of increased morbidity and mortality, especially in immunosuppressed hosts. In this review, we examine the interactions between immunobiotics-postbiotics and the immune cell populations of the respiratory mucosa. In addition, we discuss how this cross talk affects the maintenance of a normal generation of immune cells, that is crucial for the establishment of protective innate and adaptive immune responses. Particular attention will be given to the alterations in the development of phagocytic cells, T and B lymphocytes in bone marrow, spleen and thymus in immunosuppression state by protein deprivation. Furthermore, we describe our research that demonstrated that the effectiveness of immunobiotics nasal administration in accelerating the recovery of the respiratory immune response in malnourished hosts. Finally, we propose the peptidoglycan from the immunobioticLactobacillus rhamnosusCRL1505 as the key cellular component for the effects on mucosal immunity, which are unique and cannot be extrapolated to otherL. rhamnosusor probiotic strains. In this way, we provide the scientific bases for its application as a mucosal adjuvant in health plans, mainly aimed to improve the immune response of immunocompromised hosts. The search for safe vaccine adjuvants that increase their effectiveness at the mucosal level is a problem of great scientific relevance today.
STIL Endows Oncogenic and Stem-Like Attributes to Colorectal Cancer Plausibly by Shh and Wnt Signaling
Authors: Pradhan Tapas , Kumar Vikas , Surya H Evangeline , Krishna R. , John Samu , Jissa V. T. , Anjana S. , Chandramohan K. , Nair S. Asha
Published: August 2021

The discovery of a potent gene regulating tumorigenesis and drug resistance is of high clinical importance. STIL is an oncogene; however, its molecular associations and role in colorectal oncogenesis are unknown. In this study, we have explored the role of STIL gene in tumorigenesis and studied its molecular targets in colorectal cancer (CRC). STIL silencing reduced proliferation and tumor growth in CRC. Further, STIL was found to regulate stemness markers CD133 and CD44 and drug resistant markers thymidylate synthase, ABCB1, and ABCG2 both in in-vitro and in-vivo CRC models. In addition, high expression of STIL mRNA was found to be associated with reduced disease-free survival in CRC cases. Interestingly, we observed that STIL-mediated regulation of stemness and drug resistant genes is not exclusively governed by Sonic hedgehog (Shh) signaling. Remarkably, we found STIL regulate β-catenin levels through p-AKT, independent of Shh pathway. This partially answers Shh independent regulatory mechanism of cancer stem cell (CSC) markers by STIL. Our study suggests an instrumental role of STIL in molecular manifestation of CRC and progression.
HIST2H2BF Potentiates the Propagation of Cancer Stem Cells via Notch Signaling to Promote Malignancy and Liver Metastasis in Colorectal Carcinoma
Authors: Qiu Lei , Yang Xiuwei , Wu Jingyu , Huang Changzhi , Miao Yongchang , Fu Zan
Published: August 2021

Background

Growing evidence demonstrates that the initiation and progression of colorectal carcinoma (CRC) is related to the presence of cancer stem cells (CSCs). However, the mechanism through which the stem cell features of CRC cells are maintained is poorly understood. In this study, we identified the oncogenic histone cluster 2 H2B family member F (HIST2H2BF) and aimed to investigate the function of upregulated HIST2H2BF expression in maintaining the stem cell features of CRC cells, which accelerate the progression of CRC.

Methods

HIST2H2BF expression was quantified using real-time polymerase chain reaction, immunohistochemistry, and western blotting. The correlation between CpG island methylation status and HIST2H2BF re-expression was assessed through bisulfite sequencing polymerase chain reaction, methylation-specific polymerase chain reaction, and 5-Aza-dC treatment. Functional assays were performed on CRC cells and mice to investigate the HIST2H2BF-induced stem cell-like and cancer properties of CRC. Using the Notch pathway inhibitor FLI-06, the regulatory effect of HIST2H2BF on downstream Notch signaling was confirmed.

Results

HIST2H2BF was highly expressed in CRC tissues and cell lines. The reactivation of HIST2H2BF in CRC stems at least in part from the hypomethylated CpG islands. CRC patients with high HIST2H2BF expression have poor survival outcomes. Functional studies have shown that HIST2H2BF promotes CSC phenotype, malignancy, and liver metastasis through the activation of Notch signaling in CRC. Blockage of the Notch pathway reduced the stem cell-like and cancer properties.

Conclusion

Our study suggests that HIST2H2BF upregulation enhances the CSC phenotype, malignancy, and liver metastasis through the activation of Notch signaling in CRC. These results identified a new perspective on the mechanism by which the stem cell features of CRC cells are maintained and highlighted the potential novel therapeutic targets for CRC.