bluuebunny/crossref_metadata_2025 huggingface dataset:
From Motor-Output to Connectivity: An In-Depth Study of in-vitro Rhythmic Patterns in the Cockroach Periplaneta americana
Authors: David Izhak , Ayali Amir
Published: May 2021

The cockroach is an established model in the study of locomotion control. While previous work has offered important insights into the interplay among brain commands, thoracic central pattern generators, and the sensory feedback that shapes their motor output, there remains a need for a detailed description of the central pattern generators' motor output and their underlying connectivity scheme. To this end, we monitored pilocarpine-induced activity of levator and depressor motoneurons in two types of novel in-vitro cockroach preparations: isolated thoracic ganglia and a whole-chain preparation comprising the thoracic ganglia and the subesophageal ganglion. Our data analyses focused on the motoneuron firing patterns and the coordination among motoneuron types in the network. The burstiness and rhythmicity of the motoneurons were monitored, and phase relations, coherence, coupling strength, and frequency-dependent variability were analyzed. These parameters were all measured and compared among network units both within each preparation and among the preparations. Here, we report differences among the isolated ganglia, including asymmetries in phase and coupling strength, which indicate that they are wired to serve different functions. We also describe the intrinsic default gait and a frequency-dependent coordination. The depressor motoneurons showed mostly similar characteristics throughout the network regardless of interganglia connectivity; whereas the characteristics of the levator motoneurons activity were mostly ganglion-dependent, and influenced by the presence of interganglia connectivity. Asymmetries were also found between the anterior and posterior homolog parts of the thoracic network, as well as between ascending and descending connections. Our analyses further discover a frequency-dependent inversion of the interganglia coordination from alternations between ipsilateral homolog oscillators to simultaneous activity. We present a detailed scheme of the network couplings, formulate coupling rules, and review a previously suggested model of connectivity in light of our new findings. Our data support the notion that the inter-hemiganglia coordination derives from the levator networks and their coupling with local depressor interneurons. Our findings also support a dominant role of the metathoracic ganglion and its ascending output in governing the anterior ganglia motor output during locomotion in the behaving animal.
Ocean Dynamics and Topographic Upwelling Around the Aracati Seamount - North Brazilian Chain From in situ Observations and Modeling Results
Authors: Silva Marcus , Araujo Moacyr , Geber Fábio , Medeiros Carmen , Araujo Julia , Noriega Carlos , Costa da Silva Alex
Published: May 2021

The hydrodynamics and the occurrence of topographic upwelling around the northern Brazilian seamount chain were investigated. Meteorological and physical oceanographic data collected under the REVIZEE-NE Program cruises around the Aracati Bank, the major and highly productive seamount in the area, were analyzed and used to force and validate simulations using the 3D Princeton Ocean Model (3D POM). The Tropical Water mass in the top 150-m layer and the South Atlantic Central Water (SACW) beneath it and down to a depth of 670 m was present. The thickness of the barrier layer varied seasonally, being thinner (2 m) during the austral spring (October–December) and thicker (20 m) during the austral autumn (April–June) when winds were stronger. The surface mixed and isothermal layers in the austral winter (July–September) were located at depths of 84 and 96 m, respectively. During the austral spring, those layers were located at depths of 6 and 8 m, respectively. The mean wind shear energy was 9.8 × 10–4m2s–2, and the energy of the surface gravity wave break was 10.8 × 10–2m2s–2, and both served to enhance vertical mixing in the area. A permanent thermocline between the 70- and 150-m depths was present throughout the year. The isohaline distribution followed an isotherm pattern of variation, but at times, the formation of low-salinity eddies was verified on the bank slope. The 3D POM model reproduced the thermohaline structure accurately. Temperature and salinity profiles indicated the existence of vertical water displacements over the bank and along the direction of the North Brazil Current, which is the strongest western boundary current crossing the equatorial Atlantic. The kinematic structure observed in the simulations indicated vertical velocities of O (10–3m.s–1) in the upstream region of the bank during austral winter and summer seasons. During the summer, the most important vertical velocities were localized below the lower limit of the euphotic zone; while during the austral winter, these velocities were within the euphotic zone, thereby favoring primary producers.
Power Losses of Spiral Bevel Gears: An Analysis Based on Computational Fluid Dynamics
Authors: Mastrone Marco Nicola , Concli Franco
Published: May 2021

Energy efficiency is among the predominant aspects in mechanical design. Geared transmissions are widespread in several industrial applications and efficiency's improvements translate into various benefits, e.g., reduction of pollutants' emissions, better system's reliability due to lower operating temperatures, and higher power density. The possibility to compare different solutions in the preliminary stages of the design phase plays a determinant role to the achievements of these targets. In particular, Computational Fluid Dynamics (CFD) can be adopted to analyze the problem of interest overcoming the limitations of the analytical equations. On the other side, the application of numerical models to gears, in which the topology of the domain changes during operation, represents a challenging task and tailored mesh handling algorithms must be implemented. In the current paper, the power losses of a spiral bevel gear were examined numerically with an opensource tool. The predictions of the numerical models were compared with experimental data. The approach adopted shows a good computational effort making it useful for parametrical studies and, therefore, suggests being an effective tool for the analysis of the gearboxes' efficiency and lubrication.
Collagen Biosynthesis, Processing, and Maturation in Lung Ageing
Authors: Onursal Ceylan , Dick Elisabeth , Angelidis Ilias , Schiller Herbert B. , Staab-Weijnitz Claudia A.
Published: May 2021

In addition to providing a macromolecular scaffold, the extracellular matrix (ECM) is a critical regulator of cell function by virtue of specific physical, biochemical, and mechanical properties. Collagen is the main ECM component and hence plays an essential role in the pathogenesis and progression of chronic lung disease. It is well-established that many chronic lung diseases, e.g., chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) primarily manifest in the elderly, suggesting increased susceptibility of the aged lung or accumulated alterations in lung structure over time that favour disease. Here, we review the main steps of collagen biosynthesis, processing, and turnover and summarise what is currently known about alterations upon lung ageing, including changes in collagen composition, modification, and crosslinking. Recent proteomic data on mouse lung ageing indicates that, while the ER-resident machinery of collagen biosynthesis, modification and triple helix formation appears largely unchanged, there are specific changes in levels of type IV and type VI as well as the two fibril-associated collagens with interrupted triple helices (FACIT), namely type XIV and type XVI collagens. In addition, levels of the extracellular collagen crosslinking enzyme lysyl oxidase are decreased, indicating less enzymatically mediated collagen crosslinking upon ageing. The latter contrasts with the ageing-associated increase in collagen crosslinking by advanced glycation endproducts (AGEs), a result of spontaneous reactions of protein amino groups with reactive carbonyls, e.g., from monosaccharides or reactive dicarbonyls like methylglyoxal. Given the slow turnover of extracellular collagen such modifications accumulate even more in ageing tissues. In summary, the collective evidence points mainly toward age-induced alterations in collagen composition and drastic changes in the molecular nature of collagen crosslinks. Future work addressing the consequences of these changes may provide important clues for prevention of lung disease and for lung bioengineering and ultimately pave the way to novel targeted approaches in lung regenerative medicine.
Osteosarcopenia in Very Old Age Adults After Hip Fracture: A Real-World Therapeutic Standpoint
Authors: Pizzonia Monica , Casabella Andrea , Natali Marta , Petrocchi Lorena , Carmisciano Luca , Nencioni Alessio , Molfetta Luigi , Giannotti Chiara , Bianchi Gerolamo , Giusti Andrea , Santolini Federico , Monacelli Fiammetta
Published: May 2021

Loss of bone and muscle mass and strength (i. e., osteosarcopenia) is a highly prevalent clinical condition in older adults, associated with an increased risk of fragility fractures and unfavorable clinical outcomes. Although sarcopenia is a potential risk factor for osteoporosis and subsequent fracture, and the management of this hazardous duet is the key to preventing osteoporotic fracture, evidence pertaining to the treatment of sarcopenia for the purpose of preventing fragile fractures remains insufficient. Given this scenario we aimed at prospectively compare the long-term effectiveness of bisphosphonates vs. denosumab, on bone and muscle, in a cohort of old age hip fractured patients by virtue of a timely osteo-metabolic and sarcopenic assessment. Ninety-eight patients consecutively enrolled at the IRCCS Hospital San martino, Genoa, Italy, received at baseline comprehensive geriatric assessment and Bone Densitometry (DXA) with the quantitative and quantitative bone analysis and evaluation of relative skeletal muscle index (RSMI) and longitudinally after 1 year form hip surgery. The results showed a slightly and non-significant osteo-metabolic improvement in the Alendronate group compared to the Denosumab group, and a positive trend of RSMI measurements in the Denosumab group. Although preliminary in nature, this is the first report to longitudinally analyze osteosarcopenia in a real-world cohort of very old age patients after hip fracture and moved a step forward in the understanding of the best osteo-metabolic therapy for long- term treatment, exploring as well the potential dual role of denousumab as antiresorptive and muscle strength specific drug for osteosarcopenia in this vulnerable population.
Risk Factors for Mucosal Involvement in Bullous Pemphigoid and the Possible Mechanism: A Review
Authors: Chen Xinyi , Zhao Wenlin , Jin Hongzhong , Li Li
Published: May 2021

Bullous pemphigoid (BP) is the most common type of autoimmune bullous disease and is characterized by the presence of circulating anti-BP180 and/or anti-BP230 autoantibodies. Patients with BP often present with tense blisters and erythema, mainly on the trunk and limbs, but a few patients also have mucosal involvement. In this article, we discuss the fact that BP patients with mucosal involvement tend to have more serious conditions and their disease is more difficult to control. Potential risk factors for mucous involvement include earlier age at onset, drugs such as dipeptidyl peptidase-4 inhibitors, cancer, and blood/serum biomarkers, including lower eosinophil count, higher erythrocyte sedimentation rate, IgG autoantibodies against both the NH2- and COOH-termini of BP180, and the absence of anti-BP230 antibodies. IgA and C3 deposition at the dermo-epidermal junction may also be present. Understanding these risk factors may benefit earlier diagnosis of these patients and promote the development of novel treatments. What's more, it's helpful in deeper understanding of BP development and the relationship between BP and mucous membrane pemphigoid (MMP).
Responses of Soil Fungal Communities to Lime Application in Wheat Fields in the Pacific Northwest
Authors: Yin Chuntao , Schlatter Daniel C. , Kroese Duncan R. , Paulitz Timothy C. , Hagerty Christina H.
Published: May 2021

Liming is an effective agricultural practice and is broadly used to ameliorate soil acidification in agricultural ecosystems. Our understanding of the impacts of lime application on the soil fungal community is scarce. In this study, we explored the responses of fungal communities to liming at two locations with decreasing soil pH in Oregon in the Pacific Northwest using high-throughput sequencing (Illumina MiSeq). Our results revealed that the location and liming did not significantly affect soil fungal diversity and richness, and the impact of soil depth on fungal diversity varied among locations. In contrast, location and soil depth had a strong effect on the structure and composition of soil fungal communities, whereas the impact of liming was much smaller, and location- and depth-dependent. Interestingly, families Lasiosphaeriaceae, Piskurozymaceae, and Sordariaceae predominated in the surface soil (0–7.5 cm) and were positively correlated with soil OM and aluminum, and negatively correlated with pH. The family Kickxellaceae which predominated in deeper soil (15–22.5 cm), had an opposite response to soil OM. Furthermore, some taxa in Ascomycota, such as Hypocreales, Peziza and Penicillium, were increased by liming at one of the locations (Moro). In conclusion, these findings suggest that fungal community structure and composition rather than fungal diversity responded to location, soil depth and liming. Compared to liming, location and depth had a stronger effect on the soil fungal community, but some specific fungal taxa shifted with lime application.
Acid-Sensing Histidine Kinase With a Redox Switch
Authors: Inada Shinya , Okajima Toshihide , Utsumi Ryutaro , Eguchi Yoko
Published: May 2021

The EvgS/EvgA two-component signal transduction system inEscherichia coliis activated under mildly acidic pH conditions. Upon activation, this system induces the expression of a number of genes that confer acid resistance. The EvgS histidine kinase sensor has a large periplasmic domain that is required for perceiving acidic signals. In addition, we have previously proposed that the cytoplasmic linker region of EvgS is also involved in the activation of this sensor. The cytoplasmic linker region resembles a Per-ARNT-Sim (PAS) domain, which is known to act as a molecular sensor that is responsive to chemical and physical stimuli and regulates the activity of diverse effector domains. Our EvgS/EvgA reporter assays revealed that under EvgS-activating mildly acidic pH conditions, EvgS was activated only during aerobic growth conditions, and not during anaerobic growth. Studies using EvgS mutants revealed that C671A and C683A mutations in the cytoplasmic PAS domain activated EvgS even under anaerobic conditions. Furthermore, among the electron carriers of the electron transport chain, ubiquinone was required for EvgS activation. The present study proposes a model of EvgS activation by oxidation and suggests that the cytoplasmic PAS domain serves as an intermediate redox switch for this sensor.
Prevalence of Escherichia coli and Antibiotic-Resistant Bacteria During Fresh Produce Production (Romaine Lettuce) Using Municipal Wastewater Effluents
Authors: Summerlin Harvey N. , Pola Cícero C. , McLamore Eric S. , Gentry Terry , Karthikeyan Raghupathy , Gomes Carmen L.
Published: May 2021

High demand for food and water encourages the exploration of new water reuse programs, including treated municipal wastewater usage. However, these sources could contain high contaminant levels posing risks to public health. The objective of this study was to grow and irrigate a leafy green (romaine lettuce) with treated wastewater from a municipal wastewater treatment plant to track Escherichia coli and antibiotic-resistant microorganisms through cultivation and post-harvest storage to assess their fate and prevalence. Contamination levels found in the foliage, leachate, and soil were directly (p < 0.05) related to E. coli concentrations in the irrigation water. Wastewater concentrations from 177 to 423 CFU ml−1 resulted in 15–25% retention in the foliage. Leachate and soil presented means of 231 and 116% retention, respectively. E. coli accumulation on the foliage was observed (p < 0.05) and increased by over 400% during 14-day storage (4°C). From randomly selected E. coli colonies, in all four biomass types, 81 and 34% showed resistance to ampicillin and cephalothin, respectively. Reclaimed wastewater usage for leafy greens cultivation could pose potential health risks, especially considering the bacteria found have a high probability of being antibiotic resistance. Successful reuse of wastewater in agriculture will depend on appropriate mitigation and management strategies to guarantee an inexpensive, efficient, and safe water supply.
Reverse Genetic Approaches for the Generation of Full Length and Subgenomic Replicon of EV71 Virus
Authors: Yang Hang , Zhao Xiaohui , Xun Meng , Ma Chaofeng , Wang Hongliang
Published: May 2021

Enterovirus 71 (EV71) is a neurotropic pathogen that causes hand, foot, and mouth disease (HFMD) and it has been consistently associated with severe neurological, cardiac, and respiratory complications. Yet there is no specific treatment for this virus and we still know little about the viral pathogenesis. In this study, we first generated an infectious cDNA clone of EV71 virus from a patient virus strain and made a full-length virus with a NanoLuc reporter gene through reverse genetic approaches. The reporter gene of this virus is genetically stable when passaging in cells and could be used for antiviral testing. In addition, we also made subgenomic replicons (SGRs) of EV71, which lacks part of the structural genes dispensable for viral replication and showed that SGR can be used for viral replication study. Overall, these reporter viral systems are useful tools for EV71 pathogenesis study and antiviral screening.
The Potential of Flos sophorae immaturus as a Pigment-Stabilizer to Improve the Monascus Pigments Preservation, Flavor Profiles, and Sensory Characteristic of Hong Qu Huangjiu
Authors: Yang Yijin , Xia Yongjun , Song Xin , Mu Zhiyong , Qiu Huazhen , Tao Leren , Ai Lianzhong
Published: May 2021

Hong Qu Huangjiu (HQW) is distinguished by its inclusion of Monascus pigments, meaning that photosensitivity strongly affects the sensory quality of the wine. In this study, the effects of Flos sophorae immaturus (FSI) on the stability of Monascus pigments, the flavor profiles, and the sensory characteristics of HQW were investigated. After sterilization, the addition of FSI increased the preservation rate of Monascus pigments in HQW by up to 93.20%, which could be accounted for by the synergy of rutin and quercetin in FSI. The total content of the volatile flavor compounds in HQW increased significantly as the added amounts of FSI were increased, especially 3-methyl-1-butanol, 2-methyl-1-propanol, and short-chain fatty acid ethyl esters (SCFAEE). Sensory evaluation and partial least-squares regression revealed that the concentration of FSI significantly affected the aroma characteristics of HQW but had little effect on the mouthfeel. The addition of 0.9 mg/mL FSI yielded a satisfactory HQW with high scores in terms of mouthfeel and aroma. The strong correlation between fruit-aroma, full-body, and SCFAEE suggests that FSI might alter the aroma of HQW by enhancing the synthesis of SCFAEE. Summarily, treatment with FSI represents a new strategy for improving the stability of photosensitive pigments and thus adjusting the aroma of HQW or similar beverages.
The Persistent Challenge of Pneumocystis Growth Outside the Mammalian Lung: Past and Future Approaches
Authors: Cushion Melanie T. , Tisdale-Macioce Nikeya , Sayson Steven G. , Porollo Aleksey
Published: May 2021

The pathogenic fungi in the genus, Pneumocystis, have eluded attempts to continuously grow them in anex vivocultivation system. New data from transcriptomic and genomic sequencing studies have identified a myriad of absent metabolic pathways, helping to define their host obligate nature. These nutrients, factors, and co-factors are acquired from their mammalian host and provide clues to further supplementation of existing media formulations. Likewise, a new appreciation of the pivotal role for the sexual cycle in the survival and dissemination of the infection suggests that Pneumocystis species are obligated to undergo mating and sexual reproduction in their life cycle with a questionable role for an asexual cycle. The lack of ascus formation in any previous cultivation attempts may explain the failure to identify a sustainable system. Many characteristics of these ascomycetes suggest a biotrophic existence within the lungs of the mammalian hosts. In the present review, previous attempts at growing these fungiex vivoare summarized. The significance of their life cycle is considered, and a list of potential supplements based on the genomic and transcriptomic studies is presented. State of the art technologies such as metabolomics, organoids, lung-on-a chip, and air lift cultures are discussed as potential growth systems.
Random Survival Forests to Predict Disease Control for Hepatocellular Carcinoma Treated With Transarterial Chemoembolization Combined With Sorafenib
Authors: Zhong Bin-Yan , Yan Zhi-Ping , Sun Jun-Hui , Zhang Lei , Hou Zhong-Heng , Zhu Xiao-Li , Wen Ling , Ni Cai-Fang
Published: May 2021

Objectives: To use baseline variables to predict one-year disease control for patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) combined with sorafenib as initial treatment by applying a machine learning approach based on the random survival forest (RF) model.

Materials and Methods: The multicenter retrospective study included 496 patients with HCC treated with TACE combined with sorafenib between January 2014 and December 2018. The independent risk factors associated with one-year disease control (complete response, partial response, stable disease) were identified using the RF model, and their predictive importance was determined using the Gini index. Tumor response was assessed according to modified Response Evaluation Criteria in Solid Tumors.

Results: The median overall survival was 15.5 months. A total of 186 (37.5%) patients achieved positive one-year disease control. The Barcelona Clinic Liver Cancer (BCLC) stage (Gini index: 20.0), tumor size (≤7 cm, >7 cm; Gini index: 9.0), number of lobes involved (unilobar, bilobar; Gini index: 6.4), alpha-fetoprotein level (≤200 ng/dl, >200 ng/dl; Gini index: 6.1), albumin–bilirubin grade (Gini index: 5.7), and number of lesions (1, >1; Gini index: 5.3) were identified as independent risk factors, with the BCLC stage as the most important variable. The RF model achieved a higher concordance index of 0.724 compared to that for the logistic regression model (0.709).

Conclusions: The RF model is a simple and accurate approach for prediction of one-year disease control for patients with HCC treated with TACE combined with sorafenib.
The Sulfation Code of Tauopathies: Heparan Sulfate Proteoglycans in the Prion Like Spread of Tau Pathology
Authors: Mah Dylan , Zhao Jing , Liu Xinyue , Zhang Fuming , Liu Jian , Wang Lianchun , Linhardt Robert , Wang Chunyu
Published: May 2021

Tauopathies are a heterogenous family of progressive neurodegenerative diseases defined by the appearance of proteinaceous lesions within the brain composed of abnormally folded species of Microtubule Associated Protein Tau (tau). Alzheimer’s Disease (AD), the most common tauopathy, is the leading cause of cognitive decline among the elderly and is responsible for more than half of all cases of senile dementia worldwide. The characteristic pathology of many tauopathies—AD included—presents as Neurofibrillary Tangles (NFTs), insoluble inclusions found within the neurons of the central nervous system composed primarily of tau protein arranged into Paired Helical Fibrils (PHFs). The spatial extent of this pathology evolves in a remarkably consistent pattern over the course of disease progression. Among the leading hypotheses which seek to explain the stereotypical progression of tauopathies is the prion model, which proposes that the spread of tau pathology is mediated by the transmission of self-propagating tau conformers between cells in a fashion analogous to the mechanism of communicable prion diseases. Protein-glycan interactions between tau and Heparan Sulfate Proteoglycans (HSPGs) have been implicated as a key facilitator in each stage of the prion-like propagation of tau pathology, from the initial secretion of intracellular tau protein into the extracellular matrix, to the uptake of pathogenic tau seeds by cells, and the self-assembly of tau into higher order aggregates. In this review we outline the biochemical basis of the tau-HS interaction and discuss our current understanding of the mechanisms by which these interactions contribute to the propagation of tau pathology in tauopathies, with a particular focus on AD.
Computational Modeling as a Tool to Investigate PPI: From Drug Design to Tissue Engineering
Authors: Perez Juan J. , Perez Roman A. , Perez Alberto
Published: May 2021

Protein-protein interactions (PPIs) mediate a large number of important regulatory pathways. Their modulation represents an important strategy for discovering novel therapeutic agents. However, the features of PPI binding surfaces make the use of structure-based drug discovery methods very challenging. Among the diverse approaches used in the literature to tackle the problem, linear peptides have demonstrated to be a suitable methodology to discover PPI disruptors. Unfortunately, the poor pharmacokinetic properties of linear peptides prevent their direct use as drugs. However, they can be used as models to design enzyme resistant analogs including, cyclic peptides, peptide surrogates or peptidomimetics. Small molecules have a narrower set of targets they can bind to, but the screening technology based on virtual docking is robust and well tested, adding to the computational tools used to disrupt PPI. We review computational approaches used to understand and modulate PPI and highlight applications in a few case studies involved in physiological processes such as cell growth, apoptosis and intercellular communication.
Synergism of Zinc Oxide Quantum Dots with Antifungal Drugs: Potential Approach for Combination Therapy against Drug Resistant Candida albicans
Authors: Chand Preeti , Kumari Sangeeta , Mondal Neelima , Singh Surinder P. , Prasad Tulika
Published: May 2021

Candidiasis caused by Candida albicans is one of the most common microbial infections. Azoles, polyenes, allylamines, and echinocandins are classes of antifungals used for treating Candida infections. Standard drug doses often become ineffective due to the emergence of multidrug resistance (MDR). This leads to the use of higher drug doses for prolonged duration, resulting in severe toxicity (nephrotoxicity and liver damage) in humans. However, combination therapy using very low concentrations of two or more antifungal agents together, can lower such toxicity and limit evolution of drug resistance. Herein, 4–6 nm zinc oxide quantum dots (ZnO QDs) were synthesized and their in vitro antifungal activities were assessed against drug-susceptible (G1, F1, and GU4) and resistant (G5, F5, and GU5) isolates of C. albicans. In broth microdilution assay, ZnO QDs exhibited dose dependent growth inhibition between 0 – 200 µg/ml and almost 90% growth was inhibited in all Candida strains at 200 µg/ml of ZnO QDs. Synergy between ZnO QDs and antifungal drugs at sub-inhibitory concentrations of each was assessed by checkerboard analysis and expressed in terms of the fractional inhibitory concentration (FIC) index. ZnO QDs were used with two different classes of antifungals (azoles and polyenes) against Candida isolates: combination 1 (with fluconazole); combination 2 (with ketoconazole); combination 3 (with amphotericin B), and combination 4 (with nystatin). Results demonstrated that the potency of combinations of ZnO QDs with antifungal drugs even at very low concentrations of each was higher than their individual activities against the fungal isolates. The FIC index was found to be less than 0.5 for all combinations in the checkerboard assay, which confirmed synergism between sub-inhibitory concentrations of ZnO QDs (25 µg/ml) and individual antifungal drugs. Synergism was further confirmed by spot assay where cell viabilities of Candida strains were significantly reduced in all combinations, which was clearly evident from the disappearance of fungal cells on agar plates containing antifungal combinations. For safer clinical use, the in vitro cytotoxic activity of ZnO QDs was assessed against HeLa cell line and it was found that ZnO QDs were non-toxic at 25 µg/ml. Results suggested that the combination of ZnO QDs with drugs potentiate antimicrobial activity through multitargeted action. ZnO QDs could therefore offer a versatile alternative in combination therapy against MDR fungal pathogens, wherein lowering drug concentrations could reduce toxicity and their multitargeted action could limit evolution of fungal drug resistance.
Exoskeleton Active Walking Assistance Control Framework Based on Frequency Adaptive Dynamics Movement Primitives
Authors: Qiu Shiyin , Guo Wei , Zha Fusheng , Deng Jing , Wang Xin
Published: May 2021

This paper introduces a novel exoskeleton active walking assistance control framework based on frequency adaptive dynamics movement primitives (FADMPs). The FADMPs proposed in this paper is an online learning and prediction algorithm which is able to online estimate the fundamental frequency of human joint trajectory, learn the shape of joint trajectory and predict the future joint trajectory during walking. The proposed active walking assistance control framework based on FADMPs is a model-based controller which relies on the human joint torque estimation. The assistance torque provided by exoskeleton is estimated by human lower limb inverse dynamics model which is sensitive to the noise in the joint motion trajectory. To estimate a smooth joint torque profile, the joint motion trajectory must be filtered first by a lowpass filter. However, lowpass filter will introduce an inevitable phase delay in the filtered trajectory. Both simulations and experiments in this paper show that the phase delay has a significant effect on the performance of exoskeleton active assistance. The active assistant control framework based on FADMPs aims at improving the performance of active assistance control by compensating the phase delay. Both simulations and experiments on active walking assistance control show that the performance of active assistance control can be further improved when the phase delay in the filtered trajectory is compensated by FADMPs.
A Non-spiking Neuron Model With Dynamic Leak to Avoid Instability in Recurrent Networks
Authors: Rongala Udaya B. , Enander Jonas M. D. , Kohler Matthias , Loeb Gerald E. , Jörntell Henrik
Published: May 2021

Recurrent circuitry components are distributed widely within the brain, including both excitatory and inhibitory synaptic connections. Recurrent neuronal networks have potential stability problems, perhaps a predisposition to epilepsy. More generally, instability risks making internal representations of information unreliable. To assess the inherent stability properties of such recurrent networks, we tested a linear summation, non-spiking neuron model with and without a “dynamic leak”, corresponding to the low-pass filtering of synaptic input current by the RC circuit of the biological membrane. We first show that the output of this neuron model, in either of its two forms, follows its input at a higher fidelity than a wide range of spiking neuron models across a range of input frequencies. Then we constructed fully connected recurrent networks with equal numbers of excitatory and inhibitory neurons and randomly distributed weights across all synapses. When the networks were driven by pseudorandom sensory inputs with varying frequency, the recurrent network activity tended to induce high frequency self-amplifying components, sometimes evident as distinct transients, which were not present in the input data. The addition of a dynamic leak based on known membrane properties consistently removed such spurious high frequency noise across all networks. Furthermore, we found that the neuron model with dynamic leak imparts a network stability that seamlessly scales with the size of the network, conduction delays, the input density of the sensory signal and a wide range of synaptic weight distributions. Our findings suggest that neuronal dynamic leak serves the beneficial function of protecting recurrent neuronal circuitry from the self-induction of spurious high frequency signals, thereby permitting the brain to utilize this architectural circuitry component regardless of network size or recurrency.
Case Report: Bilateral Palsy of the Vocal Cords After COVID-19 Infection
Authors: Jungbauer Frederic , Hülse Roland , Lu Fei , Ludwig Sonja , Held Valentin , Rotter Nicole , Schell Angela
Published: May 2021

During the COVID-19 pandemic, adverse neurological effects have been described. In addition to unspecific neurological symptoms, cranial nerve deficits have appeared as part of SARS-CoV-2 infection. In this case report, we describe a 74-year-old patient who developed bilateral paralysis of the vocal cords some weeks following his dismissal in stable condition after COVID-19 pneumonia. After ruling out central lesions, peripheral tumors, and other possible causes, therapy was initiated with methylprednisolone, inhalations, and oxygen. The patient showed no improvement, so laterofixation after Lichtenberger was performed. The dyspnea worsened after several weeks, so a laser posterior cordectomy was performed with satisfactory outcome.
Clinical Diagnostic Criteria Have a High Impact on the Frequency of Dementia in Late-Stage Parkinson's Disease
Authors: Severiano e Sousa Catarina , Fabbri Margherita , Godinho Catarina , Simões Rita , Chendo Inês , Coelho Miguel , Martins Isabel Pavão , Ferreira Joaquim J.
Published: May 2021

Background: Cognitive impairment is a potential late feature of Parkinson's disease (PD). However, studies in patients with late-stage PD are lacking due to the particular characteristics of this population.

Objectives: To evaluate the frequency of dementia in late-stage PD patients and to assess the impact of using different diagnostic criteria.

Methods: We conducted a cross-sectional study to estimate the frequency of dementia in late-stage PD patients using the International Parkinson and Movement Disorders Society (MDS) (Level II) clinical diagnostic criteria as the primary outcome. We also applied other diagnostic criteria [MDS (Level I), DSM-IV, and DSM-5 criteria] to determine their applicability and impact on dementia frequency.

Results: 93 participants with a mean age of 75.8 years (SD 6.8) and 16.5 years (SD 7.5) of disease duration were included. 64.3% were classified as demented using the International Parkinson and Movement Disorders Society (MDS) (Level II) clinical diagnostic criteria. We observed a high discrepancy on the frequency of dementia depending on the criteria applied [6.2% with MDS (Level I), 58.8% with DSM-IV, and 72.0% with DSM-5 criteria].

Conclusions: We found a frequency of dementia below what was observed in similar populations. The particular characteristics of our sample may have contributed as protective factors for late-stage dementia. Dementia frequency varied depending on the criteria used mainly due to the presence of major depression.
Altered Metabolites in the Occipital Lobe in Migraine Without Aura During the Attack and the Interictal Period
Authors: Zhang Luping , Huang Jinwen , Zhang Zhengxiang , Cao Zhijian
Published: May 2021

Background: Although there have been many magnetic resonance spectroscopy (MRS) studies of migraine, few have focused on migraines during an attack. Here, we aimed to assess metabolite changes in the brain of patients with migraine, both during an attack and in the interictal phase.

Methods: Six patients (one man and five women, mean age: 39 ± 10 years) with migraine without aura during the attack (MWoA-DA), 13 patients (three men and 10 women, mean age: 31 ± 9 years) with migraine without aura during the interictal period (MWoA-DI), and 13 healthy controls (HC) (four men and nine women, mean age: 31 ± 9 years) were studied. All subjects underwent an MRS examination focusing on the occipital lobe. Metabolite changes were investigated among three groups.

Results: The MWoA-DA patients had lower glutathione/total creatine ratio (GSH/tCr) than the MWoA-DI patients and HC. Furthermore, MWoA-DI patients showed lower total choline/total creatine ratio (tCho/tCr) than those in the other two groups. The GSH/tCr ratio was positively correlated with attack frequency in the MWoA-DI group. The tCho/tCr ratio was positively correlated with attack frequency and Migraine Disability Assessment Scale (MIDAS) scores in the MWoA-DA group.

Conclusion: The present study suggests the existence of distinct pathophysiological states between the MWoA-DA and MWoA-DI groups. Neuronal dysfunction is a possible predisposing factor for migraine attack onset, along with oxidative stress and inflammation.
MRI With Gadolinium as a Measure of Blood-Labyrinth Barrier Integrity in Patients With Inner Ear Symptoms: A Scoping Review
Authors: Song Christopher I. , Pogson Jacob M. , Andresen Nicholas S. , Ward Bryan K.
Published: May 2021

Objective: Capillaries within the inner ear form a semi-permeable barrier called the blood-labyrinth barrier that is less permeable than capillary barriers elsewhere within the human body. Dysfunction of the blood-labyrinth barrier has been proposed as a mechanism for several audio-vestibular disorders. There has been interest in using magnetic resonance imaging (MRI) with intravenous gadolinium-based contrast agents (GBCA) as a marker for the integrity of the blood labyrinth barrier in research and clinical settings. This scoping review evaluates the evidence for using intravenous gadolinium-enhanced MRI to assess the permeability of the blood-labyrinth barrier in healthy and diseased ears.

Methods: A systematic search was conducted of three databases: PubMed, EMBASE, CINAHL PLUS. Studies were included that used GBCA to study the inner ear and permeability of the blood-labyrinth barrier. Data was collected on MRI protocols used and inner ear enhancement patterns of healthy and diseased ears in both human and animal studies.

Results: The search yielded 14 studies in animals and 53 studies in humans. In healthy animal and human inner ears, contrast-enhanced MRI demonstrated gradual increase in inner ear signal intensity over time that was limited to the perilymph. Signal intensity peaked at 100 min in rodents and 4 h in humans. Compared to controls, patients with idiopathic sudden sensorineural hearing loss and otosclerosis had increased signal intensity both before and shortly after GBCA injection. In patients with Ménière's disease and vestibular schwannoma, studies reported increased signal at 4 h, compared to controls. Quality assessment of included studies determined that all the studies lacked sample size justification and many lacked adequate control groups or blinded assessors of MRI.

Conclusions: The included studies provided convincing evidence that gadolinium crosses the blood-labyrinth barrier in healthy ears and more rapidly in some diseased ears. The timing of increased signal differs by disease. There was a lack of evidence that these findings indicate general permeability of the blood-labyrinth barrier. Future studies with consistent and rigorous methods are needed to investigate the relationship between gadolinium uptake and assessments of inner ear function and to better determine whether signal enhancement indicates permeability for molecules other than gadolinium.
Sex Differences in Anxiety: An Investigation of the Moderating Role of Sex in Performance Monitoring and Attentional Bias to Threat in High Trait Anxious Individuals
Authors: Strand Natalie , Fang Lin , Carlson Joshua M.
Published: May 2021

Anxiety disorders are more predominant in women than men, however there is a lack of understanding as to what neurocognitive mechanisms drive this sex difference. Recent investigation has found a potential moderating role of sex in the relationship between anxiety and the error related negativity (ERN)—a component of error-monitoring that is prevalent in high anxiety individuals—such that females display a positive relationship between anxiety/worry and ERN amplitude. We strove to further explore the influence of sex on the relationship between trait anxiety and performance monitoring, specifically with ERN, as well as extend this work to include another hallmark of anxiety, attentional bias to threat. To meet this end, participants performed the flanker and dot-probe tasks, respectively. We did not find a significant difference in the relationship between attention bias scores and anxiety for female vs. males participants. Furthermore, ΔERN amplitudes were greater in males compared to females, and males had more positive CRN amplitudes than females. There were no significant associations between ERN or ΔERN with anxiety in both male and female participants. However, there was a significant relationship between CRN amplitudes and trait anxiety in male but not female participants. Given these results, the effect of sex on the relationship between components of performance monitoring—namely the CRN and ERN—and anxiety may be more nuanced than the current understanding. Our study was limited to detecting medium to large sized moderation effects. Our findings may be important for future meta-analysis on sex differences in anxiety.
Orexin/Hypocretin and Histamine Cross-Talk on Hypothalamic Neuron Counts in Mice
Authors: Berteotti Chiara , Lo Martire Viviana , Alvente Sara , Bastianini Stefano , Bombardi Cristiano , Matteoli Gabriele , Ohtsu Hiroshi , Lin Jian-Sheng , Silvani Alessandro , Zoccoli Giovanna
Published: May 2021

The loss of hypothalamic neurons that produce wake-promoting orexin (hypocretin) neuropeptides is responsible for narcolepsy type 1 (NT1). While the number of histamine neurons is increased in patients with NT1, results on orexin-deficient mouse models of NT1 are inconsistent. On the other hand, the effect of histamine deficiency on orexin neuron number has never been tested on mammals, even though histamine has been reported to be essential for the development of a functional orexin system in zebrafish. The aim of this study was to test whether histamine neurons are increased in number in orexin-deficient mice and whether orexin neurons are decreased in number in histamine-deficient mice. The hypothalamic neurons expressing L-histidine decarboxylase (HDC), the histamine synthesis enzyme, and those expressing orexin A were counted in four orexin knock-out mice, four histamine-deficient HDC knock-out mice, and four wild-type C57BL/6J mice. The number of HDC-positive neurons was significantly higher in orexin knock-out than in wild-type mice (2,502 ± 77 vs. 1,800 ± 213, respectively, one-tailed t-test, P = 0.011). Conversely, the number of orexin neurons was not significantly lower in HDC knock-out than in wild-type mice (2,306 ± 56 vs. 2,320 ± 120, respectively, one-tailed t-test, P = 0.459). These data support the view that orexin peptide deficiency is sufficient to increase histamine neuron number, supporting the involvement of the histamine waking system in the pathophysiology of NT1. Conversely, these data do not support a significant role of histamine in orexin neuron development in mammals.
Dysfunction of Synaptic Vesicle Endocytosis in Parkinson’s Disease
Authors: Zou Li , Tian Ye , Zhang Zhentao
Published: May 2021

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease. It is a chronic and progressive disorder estimated to affect at least 4 million people worldwide. Although the etiology of PD remains unclear, it has been found that the dysfunction of synaptic vesicle endocytosis (SVE) in neural terminal happens before the loss of dopaminergic neurons. Recently, accumulating evidence reveals that the PD-linked synaptic genes, including DNAJC6, SYNJ1, and SH3GL2, significantly contribute to the disruptions of SVE, which is vital for the pathogenesis of PD. In addition, the proteins encoded by other PD-associated genes such as SNCA, LRRK2, PRKN, and DJ-1 also play key roles in the regulation of SVE. Here we present the facts about SVE-related genes and discussed their potential relevance to the pathogenesis of PD.
Neuropeptide Localization in Lymnaea stagnalis: From the Central Nervous System to Subcellular Compartments
Authors: Wood Ellen A. , Stopka Sylwia A. , Zhang Linwen , Mattson Sara , Maasz Gabor , Pirger Zsolt , Vertes Akos
Published: May 2021

Due to the relatively small number of neurons (few tens of thousands), the well-established multipurpose model organism Lymnaea stagnalis, great pond snail, has been extensively used to study the functioning of the nervous system. Unlike the more complex brains of higher organisms, L. stagnalis has a relatively simple central nervous system (CNS) with well-defined circuits (e.g., feeding, locomotion, learning, and memory) and identified individual neurons (e.g., cerebral giant cell, CGC), which generate behavioral patterns. Accumulating information from electrophysiological experiments maps the network of neuronal connections and the neuronal circuits responsible for basic life functions. Chemical signaling between synaptic-coupled neurons is underpinned by neurotransmitters and neuropeptides. This review looks at the rapidly expanding contributions of mass spectrometry (MS) to neuropeptide discovery and identification at different granularity of CNS organization. Abundances and distributions of neuropeptides in the whole CNS, eleven interconnected ganglia, neuronal clusters, single neurons, and subcellular compartments are captured by MS imaging and single cell analysis techniques. Combining neuropeptide expression and electrophysiological data, and aided by genomic and transcriptomic information, the molecular basis of CNS-controlled biological functions is increasingly revealed.
Minireview of Epilepsy Detection Techniques Based on Electroencephalogram Signals
Authors: Liu Guangda , Xiao Ruolan , Xu Lanyu , Cai Jing
Published: May 2021

Epilepsy is one of the most common neurological disorders typically characterized by recurrent and uncontrollable seizures, which seriously affects the quality of life of epilepsy patients. The effective tool utilized in the clinical diagnosis of epilepsy is the Electroencephalogram (EEG). The emergence of machine learning promotes the development of automated epilepsy detection techniques. New algorithms are continuously introduced to shorten the detection time and improve classification accuracy. This minireview summarized the latest research of epilepsy detection techniques that focused on acquiring, preprocessing, feature extraction, and classification of epileptic EEG signals. The application of seizure prediction and localization based on EEG signals in the diagnosis of epilepsy was also introduced. And then, the future development trend of epilepsy detection technology has prospected at the end of the article.