bluuebunny/crossref_metadata_2025 huggingface dataset:
RIG-I and MDA5 Protect Mice From Pichinde Virus Infection by Controlling Viral Replication and Regulating Immune Responses to the Infection
Authors: Brisse Morgan , Huang Qinfeng , Rahman Mizanur , Di Da , Liang Yuying , Ly Hinh
Published: December 2021

RIG-I and MDA5 are major cytoplasmic innate-immune sensor proteins that recognize aberrant double-stranded RNAs generated during virus infection to activate type 1 interferon (IFN-I) and IFN-stimulated gene (ISG) expressions to control virus infection. The roles of RIG-I and MDA5 in controlling replication of Pichinde virus (PICV), a mammarenavirus, in mice have not been examined. Here, we showed that MDA5 single knockout (SKO) and RIG-I/MDA5 double knockout (DKO) mice are highly susceptible to PICV infection as evidenced by their significant reduction in body weights during the course of the infection, validating the important roles of these innate-immune sensor proteins in controlling PICV infection. Compared to the wildtype mice, SKO and DKO mice infected with PICV had significantly higher virus titers and lower IFN-I expressions early in the infection but appeared to exhibit a late and heightened level of adaptive immune responses to clear the infection. When a recombinant rPICV mutant virus (rPICV-NPmut) that lacks the ability to suppress IFN-I was used to infect mice, as expected, there were heightened levels of IFN-I and ISG expressions in the wild-type mice, whereas infected SKO and DKO mice showed delayed mouse growth kinetics and relatively low, delayed, and transient levels of innate and adaptive immune responses to this viral infection. Taken together, our data suggest that PICV infection triggers activation of immune sensors that include but might not be necessarily limited to RIG-I and MDA5 to stimulate effective innate and adaptive immune responses to control virus infection in mice.
Removal of Different Thicknesses Influences the Repair Bond Strength of Dental Resin Composites
Authors: Yu Kai , Wan Minting , Shi Kui , Xue Longjian , Chen Zhi , Zhang Lu
Published: December 2021

This study investigates the repair bond strength of aged resin composites after removing different thicknesses, determine the repair performance using the same or different resin composites and describe the treated surfaces after ageing. Seventy simulated class I cavities were prepared in extracted human third molars were randomly divided into two groups and restored with a nanofilled (Filtek Z350) or a microhybrid (Clearfil APX) composite. Five specimens without ageing in each group acted as a positive control for microtensile bond strength (MTBS) test. After thermocycling, each group was randomly divided into two subgroups: Group RT1, 1 mm removed and Group RT3, 3 mm removed, followed by roughening. Ten specimens in each subgroup were repaired with the same or different composites, and MTBS tests were conducted. The surface roughness (Sa), and water contact angle of the remaining five specimens in each subgroup were measured. In every combination group, Group RT3 showed significantly higher MTBS values than Group RT1, and identical composite was not compulsory for higher repair bond strength. Removal thickness had no significant effect on the Sa in same composite group. In both the Z350 and APX groups, the water contact angle decreased with increasing removal thickness.
Synergetic–Complementary Use of Industrial Solid Wastes to Prepare High-Performance Rapid Repair Mortar
Authors: Li Jingwei , Xu Dong , Wang Xujiang , Wang Kun , Wang Wenlong
Published: December 2021

With the vigorous development of infrastructure engineering, there are growing demands for high-performance rapid repair mortar, especially those using environmental-friendly and low-carbon cementitious materials. Hereupon, this work explored an innovative approach for rapid repair mortar preparation using solid waste-based calcium sulfoaluminate cement. The calcium sulfoaluminate cement was first prepared via synergetic–complementary use of industrial solid wastes and then adopted to prepare rapid repair mortar by proportionally mixing with standard sand and four additives (i.e., polycarboxylate superplasticizer, lithium carbonate, boric acid, and latex powder). The mechanistic analysis indicated that the four additives comprehensively optimized the mechanical strengths, fluidity, and setting time of rapid repair mortar by adjusting the hydration process of calcium sulfoaluminate cement. The test results showed that the 2-h compressive and flexural strength, and 1-day bonding strength of the prepared rapid repair mortar were 32.5, 9.2, and 2.01 MPa, respectively, indicating excellent early-age mechanical performance. In addition, the 28-day compressive and flexural strengths of the rapid repair mortar reached 71.8 and 17.7 MPa. Finally, a life cycle assessment and economic analysis indicated that this approach achieved environmental-friendly utilization of industrial solid wastes, and cost-effective and energy-saving natures, which supports current trends towards a circular economy and green sustainable development.
The Friction and Wear Behaviours of Inconel 718 Superalloys at Elevated Temperature
Authors: Xu Zhibiao , Lu Zhijie , Zhang Jun , Li Dexiang , Liu Jihua , Lin Chengxiong
Published: December 2021

Machine parts made of nickel-based alloys usually work in high-temperature service environments such as aircraft turbines. The mechanical properties and antioxidant properties of materials tend to be reduced at high temperatures. Therefore, it is of great practical significance to reveal the wear mechanisms of materials at different temperatures. In the present investigation, the tribological behaviour of an Inconel 718 superalloy at different temperatures was investigated. First, the coefficient of friction curves obtained under different test conditions were analysed in detail to illustrate the dynamic change process of friction at high temperature. Next, the morphology of the wear surface, surface morphology of friction pairs and material transfer during friction were analysed via scanning electron microscopy 3D morphology and energy dispersive spectroscopy measurements to reveal the wear mechanisms of materials in a high-temperature environment. Finally, the microstructure of the cross section of the wear tracks was analysed by using optical microscopy electron back-scattered diffraction etc., to clarify the mechanisms of crack initiation and material removal. The results show that the friction properties of the Inconel 718 superalloy have differences at different test temperatures. Although increasing the test temperature does not necessarily aggravate the wear of the material, the oxidation of the wear surface during the friction process significantly increases. In addition, when the contact load increases, the thickness of the oxide layer and wear of the material simultaneously increase.
Cost of Myopia Correction: A Systematic Review
Authors: Foo Li Lian , Lanca Carla , Wong Chee Wai , Ting Daniel , Lamoureux Ecosse , Saw Seang-Mei , Ang Marcus
Published: December 2021

Myopia is one of the leading causes of visual impairment globally. Despite increasing prevalence and incidence, the associated cost of treatment remains unclear. Health care spending is a major concern in many countries and understanding the cost of myopia correction is the first step eluding to the overall cost of myopia treatment. As cost of treatment will reduce the burden of cost of illness, this will aid in future cost-benefit analysis and the allocation of healthcare resources, including considerations in integrating eye care (refractive correction with spectacles) into universal health coverage (UHC). We performed a systematic review to determine the economic costs of myopia correction. However, there were few studies for direct comparison. Costs related to myopia correction were mainly direct with few indirect costs. Annual prevalence-based direct costs for myopia ranged from $14-26 (USA), $56 (Iran) and $199 (Singapore) per capita, respectively (population: 274.63 million, 75.15 million and 3.79 million, respectively). Annually, the direct costs of contact lens were $198.30-$378.10 while spectacles and refractive surgeries were $342.50 and $19.10, respectively. This review provides an insight to the cost of myopia correction. Myopia costs are high from nation-wide perspectives because of the high prevalence of myopia, with contact lenses being the more expensive option. Without further interventions, the burden of illness of myopia will increase substantially with the projected increase in prevalence worldwide. Future studies will be necessary to generate more homogenous cost data and provide a complete picture of the global economic cost of myopia.
Association Between Overweight Sarcopenic Population and Acute Vertebral Osteoporotic Compression Fractures in Females: Retrospective, Cross-Sectional Study
Authors: Lee Younghun , Lee Ho-Jae , Yoon Siyeong , Shin Jaeyeon , Park Kyung-Chae , Lee So-young , Lee Soonchul
Published: December 2021

Background: This study aimed to determine whether the prevalence of acute vertebral osteoporotic compression fractures (VOCF) in the elderly population is related to the distribution of muscles and fat in the human body.

Methods: Data of acute VOCF and non-VOCF patients presenting at our institution between January 2018 and May 2020 were analyzed. Patients aged 65 years and older, who underwent body composition test and dual-energy X-ray absorptiometry at the same time were enrolled. After applying exclusion criteria, patients were divided into four groups: normal, sarcopenia without obesity, obesity without sarcopenia, and sarcopenic obesity. Body mass index ≥25 kg/m2 was considered obesity, and sarcopenia was defined as skeletal muscle index lower than 7.0 kg/m2 in males and 5.4 kg/m2 in females. The VOCF rate was analyzed between the groups.

Discussion: A total of 461 patients were included, of whom 103 were males. Among them, 163 (35.36%) had normal body composition, 151 (32.75%) had sarcopenia without obesity, 110 (23.86%) had obesity without sarcopenia, and 37 (8.03%) had sarcopenic obesity. The sarcopenic obesity group had the highest rate of acute VOCF (37.8%), which was statistically significant. Specifically, females with sarcopenic obesity and sarcopenia without obesity had significantly higher acute VOCF rates compared to those with normal body compositions. Multivariate analysis showed that sarcopenic obesity was significantly associated with acute VOCF rate overall, as well as in females.

Conclusion: Sarcopenic obesity is strongly associated with acute VOCF, especially in females, and it could be an essential criterion for the prevention of acute VOCF.
Genetic Diversity of the Symbiotic Fungus Epichloë festucae in Naturally Occurring Host Grass Populations
Authors: von Cräutlein Maria , Helander Marjo , Korpelainen Helena , Leinonen Päivi Helena , Vázquez de Aldana Beatriz R. , Young Carolyn Anne , Zabalgogeazcoa Iñigo , Saikkonen Kari
Published: December 2021

Epichloë festucae is a common symbiont of the perennial and widely distributed cool season grass, Festuca rubra. The symbiosis is highly integrated involving systemic growth of the fungus throughout above-ground host parts and vertical transmission from plant to its offspring via host seeds. However, the nature of symbiosis is labile ranging from antagonistic to mutualistic depending on prevailing selection pressures. Both the loss of fungus in the maternal host lineage and horizontal transmission through sexual spores within the host population may partly explain the detected variation in symbiosis in wild grass populations. Epichloë species are commonly considered as pathogens when they produce sexual spores and partly castrate their host plant. This is the pathogenic end of the continuum from antagonistic to mutualistic interactions. Here we examined the population genetic structure of E. festucae to reveal the gene flow, importance of reproduction modes, and alkaloid potential of the symbiotic fungus in Europe. Epichloë-species are highly dependent on the host in survival and reproduction whilst benefits to the host are largely linked to defensive mutualism attributable to fungal-origin bioactive alkaloids that negatively affect vertebrate and/or invertebrate herbivores. We detected decreased genetic diversity in previously glaciated areas compared to non-glaciated regions during the last glacial maximum period and found three major genetic clusters in E. festucae populations: southern, northeastern and northwestern Europe. Sexual reproduction may have a higher role than expected in Spanish E. festucae populations due to the predominance of unique genotypes and presence of both mating types in the region. In contrast, asexual reproduction via host seeds predominates in the Faroe Island and Finland in northern Europe due to the presence of biased mating-type ratios and large dominant genotypes in the E. festucae populations within the region. A substantially larger variation of alkaloid genotypes was observed in the fungal populations than expected, although the variability of the alkaloid genotypes within populations is considerably lower in northern than Spanish populations in southern Europe. E. festucae populations consist of different combinations of alkaloid classes from the gene clusters of ergot alkaloid and indole-terpenes, and from pyrrolopyrazine alkaloid gene. We suggest that the postglacial distribution history of the host grass, prevailing reproduction strategies of E. festucae, and local selection pressures likely explain a large part of the genetic variation observed in fungal populations among geographic regions. The identified alkaloid genotypes can be used by turfgrass breeders to improve resistance against herbivores in red fescue varieties and to develop new sustainable cultivars in Europe.
MDRSA: A Web Based-Tool for Rapid Identification of Multidrug Resistant Staphylococcus aureus Based on Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry
Authors: Chung Chia-Ru , Wang Zhuo , Weng Jing-Mei , Wang Hsin-Yao , Wu Li-Ching , Tseng Yi-Ju , Chen Chun-Hsien , Lu Jang-Jih , Horng Jorng-Tzong , Lee Tzong-Yi
Published: December 2021

As antibiotics resistance on superbugs has risen, more and more studies have focused on developing rapid antibiotics susceptibility tests (AST). Meanwhile, identification of multiple antibiotics resistance onStaphylococcus aureusprovides instant information which can assist clinicians in administrating the appropriate prescriptions. In recent years, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has emerged as a powerful tool in clinical microbiology laboratories for the rapid identification of bacterial species. Yet, lack of study devoted on providing efficient methods to deal with the MS shifting problem, not to mention to providing tools incorporating the MALDI-TOF MS for the clinical use which deliver the instant administration of antibiotics to the clinicians. In this study, we developed a web tool, MDRSA, for the rapid identification of oxacillin-, clindamycin-, and erythromycin-resistantStaphylococcus aureus. Specifically, the kernel density estimation (KDE) was adopted to deal with the peak shifting problem, which is critical to analyze mass spectra data, and machine learning methods, including decision trees, random forests, and support vector machines, which were used to construct the classifiers to identify the antibiotic resistance. The areas under the receiver operating the characteristic curve attained 0.8 on the internal (10-fold cross validation) and external (independent testing) validation. The promising results can provide more confidence to apply these prediction models in the real world. Briefly, this study provides a web-based tool to provide rapid predictions for the resistance of antibiotics onStaphylococcus aureusbased on the MALDI-TOF MS data. The web tool is available at:http://fdblab.csie.ncu.edu.tw/mdrsa/.
Cadmium Speciation Distribution Responses to Soil Properties and Soil Microbes of Plow Layer and Plow Pan Soils in Cadmium-Contaminated Paddy Fields
Authors: Hao Xiaodong , Bai Lianyang , Liu Xueduan , Zhu Ping , Liu Hongwei , Xiao Yunhua , Geng Jibiao , Liu Qianjin , Huang Lihua , Jiang Huidan
Published: December 2021

Cadmium (Cd) speciation ratio in arable land determines the Cd exposure risk and Cd uptake in crops. However, the driving mechanisms of Cd speciation change on the vertical scale of paddy fields remain poorly understood. In this study, the effects of plow layer and plow pan on Cd speciation distribution were investigated in a long-term Cd-contaminated rice ecosystem. The Cd accumulative effect within rice grain was enhanced with high levels of activated Cd speciation ratios in soils. Activated Cd speciation ratios were higher in plow layer soils, while stabilized Cd speciation ratios were elevated in plow pan soils. Soil physicochemical properties and soil microbes synergistically affected the Cd speciation changes in different ways between the two soil layers. Soil pH and organic elements in plow layer environment directly hindered the transformation of stabilized Cd speciation, while in plow pan environment, soil pH and organic elements indirectly decreased activated Cd speciation ratios and resulted in the accumulation of stabilized Cd speciation via regulating the predominant bacterial taxa. This study will improve our understanding of how soil environments regulate Cd speciation distributions in rice ecosystems and help to seek effective remediation methods of Cd-contaminated paddy fields to reduce the Cd accumulation in rice.
Coupling Root Diameter With Rooting Depth to Reveal the Heterogeneous Assembly of Root-Associated Bacterial Communities in Soybean
Authors: Luo Wen , Zai Xiaoyu , Sun Jieyu , Li Da , Li Yuanli , Li Guoqiang , Wei Gehong , Chen Weimin
Published: December 2021

Root diameter and rooting depth lead to morphological and architectural heterogeneity of plant roots; however, little is known about their effects on root-associated microbial communities. Bacterial community assembly was explored across 156 samples from three rhizocompartments (the rhizosphere, rhizoplane, and endosphere) for different diameters (0.0–0.5 mm, 0.5–1.0 mm, 1.0–2.0 mm, and>2.0 mm) and depths (0–5 cm, 5–10 cm, 10–15 cm, and 15–20 cm) of soybean [Glycine max (L.) Merrill] root systems. The microbial communities of all samples were analyzed using amplicon sequencing of bacterial 16S rRNA genes. The results showed that root diameter significantly affected the rhizosphere and endosphere bacterial communities, while rooting depth significantly influenced the rhizosphere and rhizoplane bacterial communities. The bacterial alpha diversity decreased with increasing root diameter in all three rhizocompartments, and the diversity increased with increasing rooting depth only in the rhizoplane. Clearly, the hierarchical enrichment process of the bacterial community showed a change from the rhizosphere to the rhizoplane to the endosphere, and the bacterial enrichment was higher in thinner or deeper roots (except for the roots at a depth of 15–20 cm). Network analysis indicated that thinner or deeper roots led to higher bacterial network complexity. The core and keystone taxa associated with the specific root diameter class and rooting depth class harbored specific adaptation or selection strategies. Root diameter and rooting depth together affected the root-associated bacterial assembly and network complexity in the root system. Linking root traits to microbiota may enhance our understanding of plant root-microbe interactions and their role in developing environmentally resilient root ecosystems.
Implications of Seed Vault Storage Strategies for Conservation of Seed Bacterial Microbiomes
Authors: Chandel Ankush , Mann Ross , Kaur Jatinder , Norton Sally , Edwards Jacqueline , Spangenberg German , Sawbridge Timothy
Published: December 2021

Global seed vaults are important, as they conserve plant genetic resources for future breeding to improve crop yield and quality and to overcome biotic and abiotic stresses. However, little is known about the impact of standard storage procedures, such as seed drying and cold storage on the seed bacterial community, and the ability to recover seed-associated bacteria after storage. In this study, soybean [Glycine max (L.) Merr.] seeds were analyzed to characterize changes in the bacterial community composition and culturability under varying storage conditions. The G. max bacterial microbiome was analyzed from undried seed, dried seed, and seed stored for 0, 3, 6, and 14months. Storage temperatures consisted of −20°C, 4°C, and room temperature (RT), with −20°C being commonly used in seed storage vaults globally. The seed microbiome of G. max was dominated by Gammaproteobacteria under all conditions. Undried seed was dominated by Pantoea (33.9%) and Pseudomonas (51.1%); however, following drying, the abundance of Pseudomonas declined significantly (0.9%), Pantoea increased significantly (73.6%), and four genera previously identified including Pajaroellobacter, Nesterenkonia, env.OPS_17, and Acidibacter were undetectable. Subsequent storage at RT, 4, or −20°C maintained high-abundance Genera at the majority of time points, although RT caused greater fluctuations in abundances. For many of the low-abundance Genera, storage at −20°C resulted in their gradual disappearance, whereas storage at 4°C or RT resulted in their more rapid disappearance. The changes in seed bacterial composition were reflected by cultured bacterial taxa obtained from the stored G. max seed. The main taxa were largely culturable and had similar relative abundance, while many, but not all, of the low-abundance taxa were also culturable. Overall, these results indicate that the initial seed drying affects the seed bacterial composition, suggesting that microbial isolation prior to seed drying is recommended to conserve these microbes. The standard seed storage condition of −20°C is most suitable for conservation of the bacterial seed microbiome, as this storage temperature slows down the loss of seed bacterial diversity over longer time periods, particularly low-abundance taxa.
Discovering the Influence of Microorganisms on Wine Color
Authors: Tofalo Rosanna , Suzzi Giovanna , Perpetuini Giorgia
Published: December 2021

Flavor, composition and quality of wine are influenced by microorganisms present on the grapevine surface which are transferred to the must during vinification. The microbiota is highly variable with a prevalence of non-Saccharomycesyeasts, whereasSaccharomyces cerevisiaeis present at low number. For wine production an essential step is the fermentation carried out by different starter cultures ofS. cerevisiaealone or in mixed fermentation with non-Saccharomycesspecies that produce wines with significant differences in chemical composition. During vinification wine color can be influenced by yeasts interacting with anthocyanin. Yeasts can influence wine phenolic composition in different manners: direct interactions—cell wall adsorption or enzyme activities—and/or indirectly—production of primary and secondary metabolites and fermentation products. Some of these characteristics are heritable trait in yeast and/or can be strain dependent. For this reason, the stability, aroma, and color of wines depend on strain/strains used during must fermentation.Saccharomyces cerevisiaeor non-Saccharomycescan produce metabolites reacting with anthocyanins and favor the formation of vitisin A and B type pyranoanthocyanins, contributing to color stability. In addition, yeasts affect the intensity and tonality of wine color by the action of β-glycosidase on anthocyanins or anthocyanidase enzymes or by the pigments adsorption on the yeast cell wall. These activities are strain dependent and are characterized by a great inter-species variability. Therefore, they should be considered a target for yeast strain selection and considered during the development of tailored mixed fermentations to improve wine production. In addition, some lactic acid bacteria seem to influence the color of red wines affecting anthocyanins’ profile. In fact, the increase of the pH or the ability to degrade pyruvic acid and acetaldehyde, as well as anthocyanin adsorption by bacterial cells are responsible for color loss during malolactic fermentation. Lactic acid bacteria show different adsorption capacity probably because of the variable composition of the cell walls. The aim of this review is to offer a critical overview of the roles played by wine microorganisms in the definition of intensity and tonality of wines’ color.
Structure-Function Relationship of the Disintegrin Family: Sequence Signature and Integrin Interaction
Authors: Vasconcelos Ariana A. , Estrada Jorge C. , David Victor , Wermelinger Luciana S. , Almeida Fabio C. L. , Zingali Russolina B.
Published: December 2021

Disintegrins are small cysteine-rich proteins found in a variety of snake venom. These proteins selectively modulate integrin function, heterodimeric receptors involved in cell-cell and cell-matrix interaction that are widely studied as therapeutic targets. Snake venom disintegrins emerged from the snake venom metalloproteinase and are classified according to the sequence size and number of disulfide bonds. Evolutive structure and function diversification of disintegrin family involves a stepwise decrease in the polypeptide chain, loss of cysteine residues, and selectivity. Since the structure elucidation of echistatin, the description of the structural properties of disintegrins has allowed the investigation of the mechanisms involved in integrin-cell-extracellular matrix interaction. This review provides an analysis of the structures of all family groups enabling the description of an expanded classification of the disintegrin family in seven groups. Each group presents a particular disulfide pattern and sequence signatures, facilitating the identification of new disintegrins. The classification was based on the disintegrin-like domain of the human metalloproteinase (ADAM-10). We also present the sequence and structural signatures important for disintegrin-integrin interaction, unveiling the relationship between the structure and function of these proteins.
Mixed Pulmonary Adenocarcinoma and Atypical Carcinoid: A Report of Two Cases of a Non-codified Entity With Biological Profile
Authors: Parente Paola , Rossi Antonio , Sparaneo Angelo , Fabrizio Federico Pio , Centonza Antonella , Taurchini Marco , Mazza Tommaso , Cassano Maurizio , Miscio Giuseppe , Centra Flavia , Ferretti Gian Maria , Di Micco Concetta Martina , Graziano Paolo , Muscarella Lucia Anna
Published: December 2021

Pulmonary carcinoids combined with a non-neuroendocrine component have rarely been described, and this histological subtype is not included as a specific entity in the current World Health Organization classification of pulmonary neoplasms. Here, we described the molecular and histological features of two rare cases of mixed lung neoplasms, composed of atypical carcinoid and adenocarcinoma. The targeted next-generation sequencing analysis covering single nucleotide variations, copy number variations, and transcript fusions in a total of 161 cancer genes of the two different tumor components shows a similar molecular profile of shared and private gene mutations. These findings suggest their monoclonal origin from a transformed stem/progenitor tumor cell, which acquires a divergent differentiation during its development and progression and accumulates novel, specific mutations.
Are Argonaute-Associated Tiny RNAs Junk, Inferior miRNAs, or a New Type of Functional RNAs?
Authors: Nakanishi Kotaro
Published: December 2021

The biosynthesis pathways of microRNAs (miRNAs) have been well characterized with the identification of the required components. miRNAs are synthesized from the transcripts of miRNA genes and other RNAs, such as introns, transfer RNAs, ribosomal RNAs, small nucleolar RNAs, and even viral miRNAs. These small RNAs are loaded into Argonaute (AGO) proteins and recruit the effector complexes to target mRNAs, repressing their gene expression post-transcriptionally. While mature miRNAs were defined as 19–23 nucleotides (nt), tiny RNAs (tyRNAs) shorter than 19 nt have been found to bind AGOs as equivalent or lesser miRNAs compared to their full-length mature miRNAs. In contrast, my recent study revealed that when human AGO3 loads 14 nt cleavage-inducing tyRNAs (cityRNAs), comprised of the first 14 nt of their corresponding mature miRNA, it can become a comparable slicer to AGO2. This observation raises the possibility that tyRNAs play distinct roles from their mature form. This minireview focuses on human AGO-associated tyRNAs shorter than 19 nt and discusses their possible biosynthesis pathways and physiological benefits, including how tyRNAs could avoid target-directed miRNA degradation accompanied by AGO polyubiquitination.
Bi-Anodal Transcranial Direct Current Stimulation Combined With Treadmill Walking Decreases Motor Cortical Activity in Young and Older Adults
Authors: Orcioli-Silva Diego , Islam Aisha , Baker Mark R. , Gobbi Lilian Teresa Bucken , Rochester Lynn , Pantall Annette
Published: December 2021

Background: Walking in the “real world” involves motor and cognitive processes. In relation to this, declines in both motor function and cognition contribute to age-related gait dysfunction. Transcranial direct current stimulation (tDCS) and treadmill walking (STW) have potential to improve gait, particularly during dual-task walking (DTW); walking whilst performing a cognitive task. Our aims were to analyze effects of combined anodal tDCS + STW intervention on cortical activity and gait during DTW.

Methods: Twenty-three young adults (YA) and 21 older adults (OA) were randomly allocated to active or sham tDCS stimulation groups. Participants performed 5-min of mixed treadmill walking (alternating 30 s bouts of STW and DTW) before and after a 20-min intervention of active or sham tDCS + STW. Anodal electrodes were placed over the left prefrontal cortex (PFC) and the vertex (Cz) using 9 cm2 electrodes at 0.6 mA. Cortical activity of the PFC, primary motor cortex (M1), premotor cortex (PMC), and supplementary motor area (SMA) bilaterally were recorded using a functional near-infrared spectroscopy (fNIRS) system. Oxygenated hemoglobin (HbO2) levels were analyzed as indicators of cortical activity. An accelerometer measured gait parameters. We calculated the difference between DTW and STW for HbO2 and gait parameters. We applied linear mixed effects models which included age group (YA vs. OA), stimulation condition (sham vs. active), and time (pre- vs. post-intervention) as fixed effects. Treadmill belt speed was a covariate. Partial correlation tests were also performed.

Results: A main effect of age group was observed. OA displayed higher activity bilaterally in the PFC and M1, unilaterally in the right PMC and higher gait variability than YA. M1 activity decreased in both YA and OA following active tDCS + STW. There was no overall effect of tDCS + STW on PFC activity or gait parameters. However, negative correlations were observed between changes in left PFC and stride length variability following active tDCS + STW intervention.

Conclusion: Increased activity in multiple cortical areas during DTW in OA may act as a compensatory mechanism. Reduction in M1 activity following active tDCS + STW with no observed gait changes suggests improved neural efficiency.
Using Flies to Understand Social Networks
Authors: Jezovit Jacob A. , Alwash Nawar , Levine Joel D.
Published: December 2021

Many animals live in groups and interact with each other, creating an organized collective structure. Social network analysis (SNA) is a statistical tool that aids in revealing and understanding the organized patterns of shared social connections between individuals in groups. Surprisingly, the application of SNA revealed that Drosophila melanogaster, previously considered a solitary organism, displays group dynamics and that the structure of group life is inherited. Although the number of studies investigating Drosophila social networks is currently limited, they address a wide array of questions that have only begun to capture the details of group level behavior in this insect. Here, we aim to review these studies, comparing their respective scopes and the methods used, to draw parallels between them and the broader body of knowledge available. For example, we highlight how despite methodological differences, there are similarities across studies investigating the effects of social isolation on social network dynamics. Finally, this review aims to generate hypotheses and predictions that inspire future research in the emerging field of Drosophila social networks.
Improving the Quantification of the Lateral Geniculate Nucleus in Magnetic Resonance Imaging Using a Novel 3D-Edge Enhancement Technique
Authors: Lipin Mikhail , Bennett Jean , Ying Gui-Shuang , Yu Yinxi , Ashtari Manzar
Published: December 2021

The lateral geniculate nucleus (LGN) is a small, inhomogeneous structure that relays major sensory inputs from the retina to the visual cortex. LGN morphology has been intensively studied due to various retinal diseases, as well as in the context of normal brain development. However, many of the methods used for LGN structural evaluations have not adequately addressed the challenges presented by the suboptimal routine MRI imaging of this structure. Here, we propose a novel method of edge enhancement that allows for high reliability and accuracy with regard to LGN morphometry, using routine 3D-MRI imaging protocols. This new algorithm is based on modeling a small brain structure as a polyhedron with its faces, edges, and vertices fitted with one plane, the intersection of two planes, and the intersection of three planes, respectively. This algorithm dramatically increases the contrast-to-noise ratio between the LGN and its surrounding structures as well as doubling the original spatial resolution. To show the algorithm efficacy, two raters (MA and ML) measured LGN volumes bilaterally in 19 subjects using the edge-enhanced LGN extracted areas from the 3D-T1 weighted images. The averages of the left and right LGN volumes from the two raters were 175 ± 8 and 174 ± 9 mm3, respectively. The intra-class correlations between raters were 0.74 for the left and 0.81 for the right LGN volumes. The high contrast edge-enhanced LGN images presented here, from a 7-min routine 3T-MRI acquisition, is qualitatively comparable to previously reported LGN images that were acquired using a proton density sequence with 30–40 averages and 1.5-h of acquisition time. The proposed edge-enhancement algorithm is not limited only to the LGN, but can significantly improve the contrast-to-noise ratio of any small deep-seated gray matter brain structure that is prone to high-levels of noise and partial volume effects, and can also increase their morphometric accuracy and reliability. An immensely useful feature of the proposed algorithm is that it can be used retrospectively on noisy and low contrast 3D brain images previously acquired as part of any routine clinical MRI visit.
T1 Relaxation Times in the Cortex and Thalamus Are Associated With Working Memory and Information Processing Speed in Patients With Multiple Sclerosis
Authors: Thaler Christian , Hartramph Isabelle , Stellmann Jan-Patrick , Heesen Christoph , Bester Maxim , Fiehler Jens , Gellißen Susanne
Published: December 2021

Background: Cortical and thalamic pathologies have been associated with cognitive impairment in patients with multiple sclerosis (MS).

Objective: We aimed to quantify cortical and thalamic damage in patients with MS using a high-resolution T1 mapping technique and to evaluate the association of these changes with clinical and cognitive impairment.

Methods: The study group consisted of 49 patients with mainly relapsing-remitting MS and 17 age-matched healthy controls who received 3T MRIs including a T1 mapping sequence (MP2RAGE). Mean T1 relaxation times (T1-RT) in the cortex and thalami were compared between patients with MS and healthy controls. Additionally, correlation analysis was performed to assess the relationship between MRI parameters and clinical and cognitive disability.

Results: Patients with MS had significantly decreased normalized brain, gray matter, and white matter volumes, as well as increased T1-RT in the normal-appearing white matter, compared to healthy controls (p < 0.001). Partial correlation analysis with age, sex, and disease duration as covariates revealed correlations for T1-RT in the cortex (r = −0.33, p < 0.05), and thalami (right thalamus: r = −0.37, left thalamus: r = −0.50, both p < 0.05) with working memory and information processing speed, as measured by the Symbol-Digit Modalities Test.

Conclusion: T1-RT in the cortex and thalamus correlate with information processing speed in patients with MS.
Real-Time Neuropsychological Testing Protocol for Left Temporal Brain Tumor Surgery: A Technical Note and Case Report
Authors: Tomasino Barbara , Guarracino Ilaria , Ius Tamara , Maieron Marta , Skrap Miran
Published: December 2021

Background: The risk of surgery in eloquent areas is related to neuropsychological dysfunctions. Maximizing the extent of resection increases the overall survival. The onco-functional balance is mandatory when surgery involves cognitive areas, and maximal information on the cognitive status of patients during awake surgery is needed. This can be achieved using direct cortical stimulation mapping and, in addition to this, a neuropsychological monitoring technique called real-time neuropsychological testing (RTNT). The RTNT includes testing protocols based on the area where the surgery is performed. We reported on tests used for left temporal lobe surgery and our RTNT decision tree.

Case Report: We reported our RTNT experience with a 25-year-old right-handed man with 13 years of schooling. He reported daily partial seizures. MRI revealed the presence of a low-grade glioma involving the temporo-insular cortex. The neuropsychological status presurgery which was within the normal range was combined with functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) information. Awake surgery plus RTNT was performed. Direct electrical stimulation during object naming elicited a motor speech arrest. Resection was continuously accompanied by the RTNT. The RTNT provided enriched information to the surgeon. Performance never dropped. A slight decrement in accuracy emerged for pseudoword repetition, short-term memory and working memory, phonological processing, and verbal comprehension. Total resection was performed, and the histological examination confirmed the nature of the lesion. Immediate postsurgery performance was within the normal range as it was the fMRI and DTI assessment.

Conclusion: The RTNT provides essential information that can be used online, during surgery, for clinical aims to provide the surgeon with useful feedback on the cognitive status of patients.
Quantitative Susceptibility Mapping-Derived Radiomic Features in Discriminating Multiple Sclerosis From Neuromyelitis Optica Spectrum Disorder
Authors: Yan Zichun , Liu Huan , Chen Xiaoya , Zheng Qiao , Zeng Chun , Zheng Yineng , Ding Shuang , Peng Yuling , Li Yongmei
Published: December 2021

Objectives: To implement a machine learning model using radiomic features extracted from quantitative susceptibility mapping (QSM) in discriminating multiple sclerosis (MS) from neuromyelitis optica spectrum disorder (NMOSD).

Materials and Methods: Forty-seven patients with MS (mean age = 40.00 ± 13.72 years) and 36 patients with NMOSD (mean age = 42.14 ± 12.34 years) who underwent enhanced gradient-echo T2*-weighted angiography (ESWAN) sequence in 3.0-T MRI were included between April 2017 and October 2019. QSM images were reconstructed from ESWAN, and QSM-derived radiomic features were obtained from seven regions of interest (ROIs), including bilateral putamen, globus pallidus, head of the caudate nucleus, thalamus, substantia nigra, red nucleus, and dentate nucleus. A machine learning model (logistic regression) was applied to classify MS and NMOSD, which combined radiomic signatures and demographic information to assess the classification accuracy using the area under the receiver operating characteristic (ROC) curve (AUC).

Results: The radiomics-only models showed better discrimination performance in almost all deep gray matter (DGM) regions than the demographic information-only model, with the highest AUC in DN of 0.902 (95% CI: 0.840–0.955). Moreover, the hybrid model combining radiomic signatures and demographic information showed the highest discrimination performance which achieved the AUC of 0.927 (95% CI: 0.871–0.984) with fivefold cross-validation.

Conclusion: The hybrid model based on QSM and powered with machine learning has the potential to discriminate MS from NMOSD.
Induced Neurons From Germ Cells in Caenorhabditis elegans
Authors: Marchal Iris , Tursun Baris
Published: December 2021

Cell fate conversion by the forced overexpression of transcription factors (TFs) is a process known as reprogramming. It leads to de-differentiation or trans-differentiation of mature cells, which could then be used for regenerative medicine applications to replenish patients suffering from, e.g., neurodegenerative diseases, with healthy neurons. However, TF-induced reprogramming is often restricted due to cell fate safeguarding mechanisms, which require a better understanding to increase reprogramming efficiency and achieve higher fidelity. The germline of the nematode Caenorhabditis elegans has been a powerful model to investigate the impediments of generating neurons from germ cells by reprogramming. A number of conserved factors have been identified that act as a barrier for TF-induced direct reprogramming of germ cells to neurons. In this review, we will first summarize our current knowledge regarding cell fate safeguarding mechanisms in the germline. Then, we will focus on the molecular mechanisms underlying neuronal induction from germ cells upon TF-mediated reprogramming. We will shortly discuss the specific characteristics that might make germ cells especially fit to change cellular fate and become neurons. For future perspectives, we will look at the potential of C. elegans research in advancing our knowledge of the mechanisms that regulate cellular identity, and what implications this has for therapeutic approaches such as regenerative medicine.
White Matter Characteristics of Cognitive Impairment in Tap-Test Positive Idiopathic Normal Pressure Hydrocephalus: A Diffusion Tensor Tract-Based Spatial Study
Authors: Tang Yufeng , Yuan Xiaoqin , Duan Jinfeng , Zhang Xianwen , Chen Jiao , Zhou Ying , Song Fangzhou , Zhou Dong
Published: December 2021

The present study was designed to systemically evaluate changes in the diffusion tensor imaging (DTI)-derived parameters of iNPH (idiopathic normal pressure hydrocephalus) patients with different responses to the tap test (TT), and to correlate cognitive impairment with white matter (WM) degeneration. This study included 22 iNPH patients and 14 healthy controls with structural magnetic resonance imaging (MRI) and DTI scanning. DTI was used to explore the differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) for all participants. DTI parameters were evaluated using an ROI (region of interest)-based and tract-based spatial statistics (TBSS) approach. Neuropsychological assessments and the idiopathic normal pressure hydrocephalus grading scoring scale (iNPHGS) were performed. Compared to the TT non-responders, the TT responders group had significantly lower FA values in the corpus callosum, cingulum cingulate gyrus, superior longitudinal fasciculus, and lower AD values in the right cingulum cingulate gyrus and the left posterior thalamic radiation. Besides, the MD values were significantly increased in the corpus callosum, left anterior corona radiata, and the RD values in the corpus callosum and cingulum cingulate gyrus. In addition, the cognitive improvement was negatively correlated with FA of the corpus callosum, cingulum cingulate gyrus, and MD values of the genu of corpus callosum. While, the cognitive improvement was positively related to the AD of the cingulum cingulate gyrus, superior longitudinal, and RD values of the corpus callosum, cingulum cingulate gyrus and uncinate fasciculus. The ROI specific WM lesions in iNPH patients are the underlying basis for cognitive impairment.
Intersection of Epigenetic and Immune Alterations: Implications for Fetal Alcohol Spectrum Disorder and Mental Health
Authors: Lussier Alexandre A. , Bodnar Tamara S. , Weinberg Joanne
Published: December 2021

Prenatal alcohol exposure can impact virtually all body systems, resulting in a host of structural, neurocognitive, and behavioral abnormalities. Among the adverse impacts associated with prenatal alcohol exposure are alterations in immune function, including an increased incidence of infections and alterations in immune/neuroimmune parameters that last throughout the life-course. Epigenetic patterns are also highly sensitive to prenatal alcohol exposure, with widespread alcohol-related alterations to epigenetic profiles, including changes in DNA methylation, histone modifications, and miRNA expression. Importantly, epigenetic programs are crucial for immune system development, impacting key processes such as immune cell fate, differentiation, and activation. In addition to their role in development, epigenetic mechanisms are emerging as attractive candidates for the biological embedding of environmental factors on immune function and as mediators between early-life exposures and long-term health. Here, following an overview of the impact of prenatal alcohol exposure on immune function and epigenetic patterns, we discuss the potential role for epigenetic mechanisms in reprogramming of immune function and the consequences for health and development. We highlight a range of both clinical and animal studies to provide insights into the array of immune genes impacted by alcohol-related epigenetic reprogramming. Finally, we discuss potential consequences of alcohol-related reprogramming of immune/neuroimmune functions and their effects on the increased susceptibility to mental health disorders. Overall, the collective findings from animal models and clinical studies highlight a compelling relationship between the immune system and epigenetic pathways. These findings have important implications for our understanding of the biological mechanisms underlying the long-term and multisystem effects of prenatal alcohol exposure, laying the groundwork for possible novel interventions and therapeutic strategies to treat individuals prenatally exposed to alcohol.