bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteome Profile of Myelin in the Zebrafish Brain
Authors: Siems Sophie B. , Jahn Olaf , Hoodless Laura J. , Jung Ramona B. , Hesse Dörte , Möbius Wiebke , Czopka Tim , Werner Hauke B.
Published: April 2021

The velocity of nerve conduction along vertebrate axons depends on their ensheathment with myelin. Myelin membranes comprise specialized proteins well characterized in mice. Much less is known about the protein composition of myelin in non-mammalian species. Here, we assess the proteome of myelin biochemically purified from the brains of adult zebrafish (Danio rerio), considering its increasing popularity as model organism for myelin biology. Combining gel-based and gel-free proteomic approaches, we identified > 1,000 proteins in purified zebrafish myelin, including all known constituents. By mass spectrometric quantification, the predominant Ig-CAM myelin protein zero (MPZ/P0), myelin basic protein (MBP), and the short-chain dehydrogenase 36K constitute 12%, 8%, and 6% of the total myelin protein, respectively. Comparison with previously established mRNA-abundance profiles shows that expression of many myelin-related transcripts coincides with the maturation of zebrafish oligodendrocytes. Zebrafish myelin comprises several proteins that are not present in mice, including 36K, CLDNK, and ZWI. However, a surprisingly large number of ortholog proteins is present in myelin of both species, indicating partial evolutionary preservation of its constituents. Yet, the relative abundance of CNS myelin proteins can differ markedly as exemplified by the complement inhibitor CD59 that constitutes 5% of the total zebrafish myelin protein but is a low-abundant myelin component in mice. Using novel transgenic reporter constructs and cryo-immuno electron microscopy, we confirm the incorporation of CD59 into myelin sheaths. These data provide the first proteome resource of zebrafish CNS myelin and demonstrate both similarities and heterogeneity of myelin composition between teleost fish and rodents.
Advances in Cancer Treatment by Targeting the Neddylation Pathway
Authors: Gai Wenbin , Peng Zhiqiang , Liu Cui Hua , Zhang Lingqiang , Jiang Hong
Published: April 2021

Developmental down-regulation protein 8 (NEDD8), expressed by neural progenitors, is a ubiquitin-like protein that conjugates to and regulates the biological function of its substrates. The main target of NEDD8 is cullin-RING E3 ligases. Upregulation of the neddylation pathway is closely associated with the progression of various tumors, and MLN4924, which inhibits NEDD8-activating enzyme (NAE), is a promising new antitumor compound for combination therapy. Here, we summarize the latest progress in anticancer strategies targeting the neddylation pathway and their combined applications, providing a theoretical reference for developing antitumor drugs and combination therapies.
Cis-Repression of Foxq1 Expression Affects Foxf2-Mediated Gene Expression in Palate Development
Authors: Xu Jingyue , Liu Han , Lan Yu , Jiang Rulang
Published: April 2021

Disruption of FOXF2, encoding a member of the Forkhead family transcription factors, has been associated with cleft palate in humans and mice. FOXF2 is located in a conserved gene cluster containing FOXQ1, FOXF2, and FOXC1. We found that expression of Foxq1 is dramatically upregulated in the embryonic palatal mesenchyme in Foxf2–/– mouse embryos. We show here that the Foxf2 promoter-deletion mutation caused dramatically increased expression of the cis-linked Foxq1 allele but had little effect on the Foxq1 allele in trans. We analyzed effects of the Foxf2 mutation on the expression of other neighboring genes and compared those effects with the chromatin domain structure and recently identified enhancer-promoter associations as well as H3K27ac ChIP-seq data. We show that the Foxf2 mutation resulted in significantly increased expression of the Foxq1 and Exoc2 genes located in the same topologically associated domain with Foxf2 but not the expression of the Foxc1 and Gmds genes located in the adjacent chromatin domain. We inactivated the Foxq1 gene in mice homozygous for a Foxf2 conditional allele using CRISPR genome editing and generated (Foxf2/Foxq1)+/– mice with loss-of-function mutations in Foxf2 and Foxq1 in cis. Whereas the (Foxf2/Foxq1)–/– mice exhibited cleft palate at birth similar as in the Foxf2–/– mice, systematic expression analyses of a large number of Foxf2-dependent genes revealed that the (Foxf2/Foxq1)–/– embryos exhibited distinct effects on the domain-specific expression of several important genes, including Foxf1, Shox2, and Spon1, in the developing palatal shelves compared with Foxf2–/– embryos. These results identify a novel cis-regulatory effect of the Foxf2 mutation and demonstrate that cis-regulation of Foxq1 contributed to alterations in palatal gene expression in Foxf2–/– embryos. These results have important implications for interpretation of results and mechanisms from studies of promoter- or gene-deletion alleles. In addition, the unique mouse lines generated in this study provide a valuable resource for understanding the cross-regulation and combinatorial functions of the Foxf2 and Foxq1 genes in development and disease.
Potential of Maritime Transport for Ocean Liming and Atmospheric CO2 Removal
Authors: Caserini Stefano , Pagano Dario , Campo Francesco , Abbà Antonella , De Marco Serena , Righi Davide , Renforth Phil , Grosso Mario
Published: April 2021

Proposals to increase ocean alkalinity may make an important contribution to meeting climate change net emission targets, while also helping to ameliorate the effects of ocean acidification. However, the practical feasibility of spreading large amounts of alkaline materials in the seawater is poorly understood. In this study, the potential of discharging calcium hydroxide (slaked lime, SL) using existing maritime transport is evaluated, at the global scale and for the Mediterranean Sea. The potential discharge of SL from existing vessels depends on many factors, mainly their number and load capacity, the distance traveled along the route, the frequency of reloading, and the discharge rate. The latter may be constrained by the localized pH increase in the wake of the ship, which could be detrimental for marine ecosystems. Based on maritime traffic data from the International Maritime Organization for bulk carriers and container ships, and assuming low discharge rates and 15% of the deadweight capacity dedicated for SL transport, the maximum SL potential discharge from all active vessels worldwide is estimated to be between 1.7 and 4.0 Gt/year. For the Mediterranean Sea, based on detailed maritime traffic data, a potential discharge of about 186 Mt/year is estimated. The discharge using a fleet of 1,000 new dedicated ships has also been discussed, with a potential distribution of 1.3 Gt/year. Using average literature values of CO2 removal per unit of SL added to the sea, the global potential of CO2 removal from SL discharge by existing or new ships is estimated at several Gt/year, depending on the discharge rate. Since the potential impacts of SL discharge on the marine environment in the ships' wake limits the rate at which SL can be applied, an overview of methodologies for the assessment of SL concentration in the wake of the ships is presented. A first assessment performed with a three-dimensional non-reactive and a one-dimensional reactive fluid dynamic model simulating the shrinking of particle radii, shows that low discharge rates of a SL slurry lead to pH variations of about 1 unit for a duration of just a few minutes.
French Science Communication on YouTube: A Survey of Individual and Institutional Communicators and Their Channel Characteristics
Authors: Debove Stéphane , Füchslin Tobias , Louis Tania , Masselot Pierre
Published: April 2021

Science videos on YouTube attract millions of viewers each month, but little is known about who the content producers are, how they work and what their motivations and qualifications are. Here, we analyze the characteristics of 622 French YouTube science channels and 70,795 science videos in French, and complement this analysis with a survey of 180 of these youtubers. We focus on three questions: who are the science communicators (sociodemographics, resources, and goals), what are the characteristics of their channels, and are there differences between institutional and non-institutional communicators. We show that French science communicators on YouTube are mostly young men, highly qualified and usually talking about their topic of expertize. Many of them do not earn enough money to make a living out of this activity and have to use personal money to run their channels. At the same time, many are not interested in making this activity their main source of income. Their main goal is to share science and stimulate curiosity, as opposed to teach and entertain. While a small number of channels account for most of the views and subscribers, together they are able to cover a lot of scientific disciplines, with individuals usually focusing on a couple of fields and institutions talking about more diverse subjects. Institutions seem to have less success on YouTube than individuals, a result visible both in the number of subscribers and engagement received in videos (likes and comments). We discuss the potential factors behind this discrepancy, such as the lack of personality of institutional channels, the high number of topics they cover or the fact that institutions usually have an additional goal compared to individuals: to present and promote the institution itself. A video version of this article has been recorded and made available here: https://stephanedebove.net/youtube
Longitudinal Speech Biomarkers for Automated Alzheimer's Detection
Authors: Laguarta Jordi , Subirana Brian
Published: April 2021

We introduce a novel audio processing architecture, the Open Voice Brain Model (OVBM), improving detection accuracy for Alzheimer's (AD) longitudinal discrimination from spontaneous speech. We also outline the OVBM design methodology leading us to such architecture, which in general can incorporate multimodal biomarkers and target simultaneously several diseases and other AI tasks. Key in our methodology is the use of multiple biomarkers complementing each other, and when two of them uniquely identify different subjects in a target disease we say they are orthogonal. We illustrate the OBVM design methodology by introducing sixteen biomarkers, three of which are orthogonal, demonstrating simultaneous above state-of-the-art discrimination for two apparently unrelated diseases such as AD and COVID-19. Depending on the context, throughout the paper we use OVBM indistinctly to refer to the specific architecture or to the broader design methodology. Inspired by research conducted at the MIT Center for Brain Minds and Machines (CBMM), OVBM combines biomarker implementations of the four modules of intelligence: The brain OS chunks and overlaps audio samples and aggregates biomarker features from the sensory stream and cognitive core creating a multi-modal graph neural network of symbolic compositional models for the target task. In this paper we apply the OVBM design methodology to the automated diagnostic of Alzheimer's Dementia (AD) patients, achieving above state-of-the-art accuracy of 93.8% using only raw audio, while extracting a personalized subject saliency map designed to longitudinally track relative disease progression using multiple biomarkers, 16 in the reported AD task. The ultimate aim is to help medical practice by detecting onset and treatment impact so that intervention options can be longitudinally tested. Using the OBVM design methodology, we introduce a novel lung and respiratory tract biomarker created using 200,000+ cough samples to pre-train a model discriminating cough cultural origin. Transfer Learning is subsequently used to incorporate features from this model into various other biomarker-based OVBM architectures. This biomarker yields consistent improvements in AD detection in all the starting OBVM biomarker architecture combinations we tried. This cough dataset sets a new benchmark as the largest audio health dataset with 30,000+ subjects participating in April 2020, demonstrating for the first time cough cultural bias.
Using Change Models to Envision Better Applications of Animal Behavior Research in Conservation Management and Beyond
Authors: Greggor Alison L. , Berger-Tal Oded , Swaisgood Ronald R. , Cooke Steven J. , DeVault Travis L. , Fernández-Juricic Esteban , Gienapp Anne , Hall Suzanne , Hostetter Cameron , Owen Megan A. , Rankin Shannon , Ruppert Kirstie A. , Swaddle John P. , Blumstein Daniel T.
Published: April 2021

While most animal behavior researchers have mastered the process of knowledge creation, generating knowledge that can readily be applied requires a different set of skills. The process and timeframe of fundamental scientific knowledge production is often not relevant to those who might apply it, such as conservation or wildlife managers. Additionally, the complex challenges that policy makers, managers and practitioners face are often not adequately communicated to and among scientists. This mutual disconnect in discourse, relationships, common terms, and practices is especially apparent when animal behavior researchers seek to have applied impact. We argue that bridging the complex implementation gap in animal behavior requires a formalized vision for change. We turn to change model theory, a tool commonly used in other fields for identifying the links between actions and outcomes necessary for enacting large-scale change. We focus on the subfield of conservation behavior with a change model that outlines specific ways to improve collaboration and coordination between animal behavior science and conservation practice. We present this targeted change model, review each strategy the model outlines, and highlight pressing actions that people from various career stages and backgrounds can take. We encourage researchers to further the alignment of science with management needs by developing the proper communication mechanisms for improved cultural exchange and plan future change model efforts directly targeting managers. Beyond the conservation behavior change model we present, we also discuss the broad applicability of change models to enhance the application of academic research to other fields. Fundamental science researchers are increasingly required to show impact of their work on society; the change model process we describe here can enable further impact.
Modulating the Microbiota as a Therapeutic Intervention for Type 2 Diabetes
Authors: Huda M. Nazmul , Kim Myungsuk , Bennett Brian J.
Published: April 2021

Mounting evidence suggested that the gut microbiota has a significant role in the metabolism and disease status of the host. In particular, Type 2 Diabetes (T2D), which has a complex etiology that includes obesity and chronic low-grade inflammation, is modulated by the gut microbiota and microbial metabolites. Current literature supports that unbalanced gut microbial composition (dysbiosis) is a risk factor for T2D. In this review, we critically summarize the recent findings regarding the role of gut microbiota in T2D. Beyond these associative studies, we focus on the causal relationship between microbiota and T2D established using fecal microbiota transplantation (FMT) or probiotic supplementation, and the potential underlying mechanisms such as byproducts of microbial metabolism. These microbial metabolites are small molecules that establish communication between microbiota and host cells. We critically summarize the associations between T2D and microbial metabolites such as short-chain fatty acids (SCFAs) and trimethylamine N-Oxide (TMAO). Additionally, we comment on how host genetic architecture and the epigenome influence the microbial composition and thus how the gut microbiota may explain part of the missing heritability of T2D found by GWAS analysis. We also discuss future directions in this field and how approaches such as FMT, prebiotics, and probiotics supplementation are being considered as potential therapeutics for T2D.
Sono-Assisted Alkali and Dilute Acid Pretreatment of Phragmites karka (Tall Reed Grass) to Enhance Enzymatic Digestibility for Bioethanol Conversion
Authors: Ummalyma Sabeela Beevi , Sahoo Dinabandhu , Pudiyamadam Anoop , Adarsh Velayudhanpillai Prasannakumari , Sukumaran Rajeev K. , Bhaskar Thallada , Parida Ajay
Published: April 2021

Phragmites is the tallest energy crop found as an invasive species worldwide and considered as waste biomass. The present study evaluated the potential of the aquatic biomass Phragmites karka grown from two different lakes as feedstock for biofuel production. A comparative study of biomass was conducted from Chilika Lake and Loktak Lake, India. The methodology involves dilute acid, sono-assisted alkali pretreatment, and hydrolyzed biomass with commercial cellulase. SEM, XRD, and FTIR analysis were performed for the biomass physicochemical studies and confirmed that alterations occurred in the biomass structure, assisting the hydrolysis process. The enzymatic hydrolysis result showed that the highest of reducing sugar yield of 79% was obtained from biomass loading of 10% and 1% w/v alkali with a sonication frequency of 20 kHz for 25 min. Acid pretreatment released maximal reducing sugar yield of 73% attained from biomass loading of 20% and 0.5% w/v acid. Composition analysis of biomass showed that cellulose content increased from 36% to 46%. Sono-assisted alkali pretreatment solubilized 40% of lignin content compared to untreated biomass. Final ethanol recovery from the biomass is 78% fermentation efficiency from glucose. The data indicate that exploiting tall reed grass as a bioenergy raw material can be a viable approach for sustainable utilization of invasive grass/waste biomass for biorefineries, which helps control invasive weeds and management of waste.
Non-woody Biomass as Sources of Nanocellulose Particles: A Review of Extraction Procedures
Authors: Owonubi Shesan J. , Agwuncha Stephen C. , Malima Nyemaga M. , Shombe Ginena B. , Makhatha Elizabeth M. , Revaprasadu Neerish
Published: April 2021

Nanocellulose has been reported to be a very useful biomaterial with applications in biomedical, pharmaceutical, built industry, automobile, aerospace and many more. Its advantages over synthetic fibers include renewability, energy efficiency, cost effectiveness, biodegradability and good mechanical and thermal properties. However, the production of cellulose nanoparticles (CNPs) has focused more on woody plant sources. Non-woody biomass constitutes a large group of plant sources that are yet to be given the proper attention for utilization as raw material for nanocellulose particle production. This group of lignocellulosic biomasses is generally obtained as waste from farming activities, home gardens or office wastes. They are majorly composed of cellulose, hemicellulose, and lignin. However, their composition varies widely from one plant source to another. The variation in their composition results in limitations in the procedures employed in extraction of CNPs and of processing of the extracted CNPs. This means that different biomasses may have different ways by which CNPs are extracted from them. Therefore, this review intends to x-ray these variations, its effect on the structural properties of extracted CNPs and possible ways such limitations can be mitigated.
Life-Cycle Assessment of Sector-Coupled National Energy Systems: Environmental Impacts of Electricity, Heat, and Transportation in Germany Till 2050
Authors: Baumgärtner Nils , Deutz Sarah , Reinert Christiane , Nolzen Niklas , Kuepper Lucas Elias , Hennen Maike , Hollermann Dinah Elena , Bardow André
Published: April 2021

National energy models provide decarbonization strategies. Most national energy models focus on costs and greenhouse gas emissions only. However, this focus carries the risk that burdens shift to other environmental impacts. Energy models have therefore been extended by life-cycle assessment (LCA). Furthermore, deep decarbonization is only possible by targeting all high-emission sectors. Thus, we present a holistic national energy model that includes high-emission sectors and LCA. The model provides detailed environmental impacts for electricity, heat, and transport processes in Germany for meeting the climate targets up to 2050. Our results show that renewable energies and storage are key technologies for decarbonized energy systems. Furthermore, sector coupling is crucial and doubles electricity demand. Our LCA shows that environmental impacts shift from operation to infrastructure highlighting the importance of an impact assessment over the full life cycle. Decarbonization leads to many environmental cobenefits; however, it also increases freshwater ecotoxicity and depletion of metal and mineral resources. Thus, holistic planning of decarbonization strategies should also consider other environmental impacts.
Barriers and Opportunities for Actionable Knowledge Production in Drought Risk Management: Embracing the Frontiers of Co-production
Authors: Grainger Sam , Murphy Conor , Vicente-Serrano Sergio M.
Published: April 2021

Drought risks pose serious threats to socio-ecological systems, built environments, livelihoods and human wellbeing. Managing these risks requires long-term collaboration between diverse groups with different values, interests and forms of knowledge. Funders, researchers and practitioners have increasingly advocated for collaborative models of knowledge production in which all participants recognise the multiple ways of understanding drought risk and strive to co-create knowledge for decision making. Such transdisciplinary research approaches aim to develop and sustain more equitable and meaningful interactions between scientific and societal actors, and have been shown to increase knowledge use and build resilience to climate variability. In practice, however, collaborations around drought remain largely science-driven and, as a result, can struggle to produce actionable knowledge necessary to better manage drought risk. This article draws from drought studies and related transdisciplinary fields to highlight common barriers inhibiting actionable knowledge production across a broad range of drought risk management contexts. We also propose opportunities for improved knowledge production that can guide researchers, practitioners and funders seeking to engage in transdisciplinary work. Diverse understandings of drought risk have hindered widespread advances in knowledge production and resilience building. We argue for multi-disciplinary researchers to come together with stakeholders and focus on creating inclusive and context-driven environments. While not appropriate or cost-effective in all situations, co-production between researchers, practitioners and other stakeholder groups offers opportunities for actionable management plans and policies that reflect the complex and contested problem framings and socio-ecological contexts in which droughts impact society.
Low Diffusive Methane Emissions From the Main Channel of a Large Amazonian Run-of-the-River Reservoir Attributed to High Methane Oxidation
Authors: Sawakuchi Henrique O. , Bastviken David , Enrich-Prast Alex , Ward Nicholas D. , Camargo Plínio B. , Richey Jeffrey E.
Published: April 2021

The global development of hydropower dams has rapidly expanded over the last several decades and has spread to historically non-impounded systems such as the Amazon River’s main low land tributaries in Brazil. Despite the recognized significance of reservoirs to the global methane (CH4) emission, the processes controlling this emission remain poorly understood, especially in Tropical reservoirs. Here we evaluate CH4 dynamics in the main channel and downstream of the Santo Antônio hydroelectric reservoir, a large tropical run-of-the-river (ROR) reservoir in Amazonia. This study is intended to give a snapshot of the CH4 dynamics during the falling water season at the initial stage after the start of operations. Our results show substantial and higher CH4 production in reservoirs’ littoral sediment than in the naturally flooded areas downstream of the dam. Despite the large production in the reservoir or naturally flooded areas, high CH4 oxidation in the main channel keep the concentration and fluxes of CH4 in the main channel low. Similar CH4 concentrations in the reservoir and downstream close to the dam suggest negligible degassing at the dam, but stable isotopic evidence indicates the presence of a less oxidized pool of CH4 after the dam. ROR reservoirs are designed to disturb the natural river flow dynamics less than traditional reservoirs. If enough mixing and oxygenation remain throughout the reservoir’s water column, naturally high CH4 oxidation rates can also remain and limit the diffusive CH4 emissions from the main channel. Nevertheless, it is important to highlight that our results focused on emissions in the deep and oxygenated main channel. High emissions, mainly through ebullition, may occur in the vast and shallow areas represented by bays and tributaries. However, detailed assessments are still required to understand the impacts of this reservoir on the annual emissions of CH4.
Case Report: Compound Heterozygous Variants in MOCS3 Identified in a Chinese Infant With Molybdenum Cofactor Deficiency
Authors: Tian Qi , Cao Yang , Shu Li , Chen Yongjun , Peng Ying , Wang Yaqin , Chen Yuanyuan , Wang Hua , Mao Xiao
Published: April 2021

Background: The molybdenum cofactor (Moco) deficiency in humans results in the inactivity of molybdenum-dependent enzymes and is caused by pathogenic variants in MOCS1 (Molybdenum cofactor synthesis 1), MOCS2 (Molybdenum cofactor synthesis 2), and GPHN (Gephyrin). These genes along with MOCS3 (Molybdenum cofactor synthesis 3) are involved in Moco biosynthesis and providing cofactors to Moco-dependent enzymes. Until now, there was no study to confirm that MOCS3 is a causative gene of Moco deficiency.

Methods: Detailed clinical information was collected in the pedigree. The Whole-exome sequencing (WES) accompanied with Sanger sequencing validation were performed.

Results: We described the clinical presentations of an infant, born to a non-consanguineous healthy family, diagnosed as having MOCS3 variants caused Moco deficiency and showing typical features of Moco deficiency including severe neurologic symptoms and cystic encephalomalacia in the brain MRI, resulting in neonatal death. Compound heterozygous variants in the MOCS3 gene were identified by WES. Positive sulfite and decreased levels of uric acid in plasma and urine were detected.

Conclusion: To our knowledge, this is the first case of MOCS3 variants causing Moco deficiency. Our study may contribute to genetic diagnosis of Moco deficiency and future genetic counseling.
Plasma Functionalized Scaffolds of Polyhydroxybutyrate Electrospun Fibers for Pancreatic Beta Cell Cultures
Authors: Cortés-Ortiz Emma , Olayo-Valles R. , Rodríguez-Talavera Rogelio , González-Torres Maykel , Vargas-Muñoz Susana , Olayo R. , Godinez-Fernández R. , Uribe Juárez Omar Eduardo , Morales-Corona Juan
Published: April 2021

Fibrous scaffolds based on biodegradable and biocompatible polyhydroxybutyrate (PHB) were produced by electrospinning. The scaffolds were coated by a thin solid film of polypyrrole, PPyI, deposited by plasma polymerization technique. FTIR and Raman spectroscopy results confirm the presence of PPyI on the PHB fibers, in FTIR can be show the signal of the NH2 groups characteristic of the polypyrrole, so Raman show a broad band due to fluorescence from the PPyI coating. The morphology of the scaffolds was characterized by scanning electron microscopy, and the average fiber diameter of PHB is (2.68 ± 1.69) μm, also the average fibers diameter of PHB-PPyI is (3.57 ± 1.36) μm, the comparation of the average fibers diameter of coated and uncoated indicates that the average PPyI coated thickness is 0.45 μm. Crystallinity of the PHB fibers was characterized by X-ray diffraction and differential scanning calorimetry, the degree of crystallinity is estimated at 70%. Pancreatic beta cells (from the RIN-M cell line) were cultured on PHB and PHB-PPyI scaffolds. Cell viability results showed that the surface modified material is a good cell culture substrate for beta cells.
Nanoindentation of Nanoglasses Tested by Molecular Dynamics Simulations: Influence of Structural Relaxation and Chemical Segregation on the Mechanical Response
Authors: Adjaoud Omar , Albe Karsten
Published: April 2021

We present molecular dynamics simulations of nanoindentation in order to investigate the effects of segregation and structural relaxation on the mechanical properties of Cu64Zr36 nanoglasses prepared by particle consolidation and long-time annealing. Our analysis of load-displacement curves shows that the effective elastic modulus of nanoglasses is lower than that of their homogeneous metallic glass counterpart. This is mainly because of the defective short-range order present in the glass-glass interface, but to a lesser extend due to chemical inhomogeneities. Structural relaxation obtained by long-time annealing (500 ns) at 0.8 Tg leads to a shift from a homogeneous deformation to a mix of homogeneous deformation and shear bands. The obtained hardness values of annealed nanoglass are comparable to those of homogenous glass samples, but significantly higher as compared to juvenile as-prepared nanoglass samples. The results are discussed in the context of recent nanonindentation experiments.
Tensile Performance of High Ductility Cementitious Composites With Recycled Powder From C&D Waste
Authors: Ji Jing , Song Huayu , Jiang Liangqin , Ren Hongguo , Zhang Yunfeng , Liu Yingchun
Published: April 2021

The effects of recycled powder (RP) on hydration, micro-structures, compressive strength and tensile properties of high-ductility cementitious composites (HDCC) were studied. Three mass ratios of RP ranging from 10, 30 to 60% were employed to partially replace the cement. The hydration kinetics of RP-amended matrix was measured to investigate the influence of RP on the cementitious hydration process and the phase development was quantified by the thermal gravimetric analysis. Mechanical properties, including the compressive and tensile properties of HDCCs were obtained at 28 days. The morphology of reinforced polyethylene fiber at the fracture surface was obtained by the environmental scanning electron microscope (SEM) analysis.
Gut Structure and Microbial Communities in Sirex noctilio (Hymenoptera: Siricidae) and Their Predicted Contribution to Larval Nutrition
Authors: Li Jiale , Li Chengcheng , Wang Ming , Wang Lixiang , Liu Xiaobo , Gao Chenglong , Ren Lili , Luo Youqing
Published: April 2021

The European woodwasp, Sirex noctilio Fabricius, is a major invasive quarantine pest that attacks and kills pine trees outside of its native range. Insect gut structure and gut microbiota play crucial roles in various life activities. Despite a few reports in nutrition and survival, an extensive study on the S. noctilio larval gut microbiome is lacking. We studied the gut structure using a stereo microscope and used high throughput sequencing of the bacterial 16S rRNA genes and fungal internal transcribed spacer 2 (ITS2) regions to investigate gut microbiota in different developmental stages of S. noctilio, including larvae, adults, and larval frass. We used PICRUSt2 to predict the functional profiles. The larval gut was thin and thread-like from the oral cavity to the anus, carrying few xylem particles in the crop. Pseudomonas, Ralstonia, and Burkholderia s.l were the dominant bacteria in the guts of larvae, adults, and frass, respectively. Even though Pseudomonas was the most abundant among all bacteria, Zoogloea, Ruminobacter, and Nitrosospira, which might be involved in degrading organic matter and fixing nitrogen occurred exclusively in the larval gut indicating their possible role in the growth and development of larvae in pine tree xylem. Fungal communities did not change significantly across different developmental stages or the frass. Amylostereum was dominant in the woodwasp’s larval gut. Functional prediction of bacterial and fungal communities revealed that they may encod enzymes involved in degrading lignocellulose and fixing nitrogen. Ours is the first study that compares gut microbial communities present in S. noctilio larvae, adults, and frass. This study could provide an understanding of larval nutrient acquisition in nutrient-deficient host xylem to some extent. Our study may unlock novel strategies for the development of pest management approaches based on interfering with the gut microbiota and restricting their role in larval survival and development.
Identification of an Invertase With High Specific Activity for Raffinose Hydrolysis and Its Application in Soymilk Treatment
Authors: Liu Juanjuan , Cheng Jing , Huang Min , Shen Chen , Xu Ke , Xiao Yazhong , Pan Wenjuan , Fang Zemin
Published: April 2021

The hydrolyzation of raffinose into melibiose by using invertases under mild conditions improves the nutritional value of soybean products. However, this strategy has received little attention because a suitable invertase remains lacking. In this study, a novel invertase named InvDz13 was screened and purified from Microbacterium trichothecenolyticum and characterized. InvDz13 was one of the invertases with the highest specific activity toward raffinose. Specifically, it had a specific activity of 229 U/mg toward raffinose at pH 6.5 and 35°C. InvDz13 retained more than 80% of its maximum activity at pH 5.5–7.5 and 25–40°C and was resistant to or stimulated by most cations that presented in soymilk. In soymilk treated with InvDz13 under mild conditions, melibiose concentration increased from 3.1 ± 0.2 to 6.1 ± 0.1 mM due to raffinose hydrolyzation by InvDz13. Furthermore, the prebiotic property of InvDz13-treated soymilk was investigated via in vitro fermentation by human gut microbiota. Results showed that InvDz13 treatment increased the proportion of the beneficial bacteria Bifidobacterium and Lactobacillus by 1.6- and 3.7-fold, respectively. By contrast, the populations of Escherichia and Collinsella decreased by 1.8- and 11.7-fold, respectively. Thus, our results proved that the enzymatic hydrolysis of raffinose in soymilk with InvDz13 was practicable and might be an alternative approach to improving the nutritional value of soymilk.
MiR-490-3p Silences CDK1 and Inhibits the Proliferation of Colon Cancer Through an LLPS-Dependent miRISC System
Authors: Qin Da , Wei Rui , Zhu Shengtao , Min Li , Zhang Shutian
Published: April 2021

Liquid-liquid phase separation (LLPS) is a burgeoning concept in cell biology, which was associated with miRISC machinery. However, most studies about LLPS are based on overexpression of core proteins, which is far away from nature condition of cells, whether miRISC underwent LLPS under biological condition remains unknown. Taking miR-490-3p and its target CDK1 as an example, we revealed without overexpression of any protein components, miRISC functioned in an LLPS-depend manner. We firstly found miRISC has liquid-like properties in colon cancer (CC) cells and could fulfill common LLPS criteria under overexpression condition. Then, RIP was performed to confirm miR-490-3p is actually functioning in miRISC. RT-qPCR, western blot and luciferase assays were performed and found miR-490-3p could significantly decrease expression of CDK1 in both RNA and protein levels. However, without overexpression of miRISC components, when treating CC cells with 1,6-hexanediol(1,6-HD), a widely used LLPS inhibitor, the silence effects of miR-490-3p to CDK1 were totally abolished, no matter in RNA, protein or luciferase levels, suggesting that miRISC functions in an LLPS-depend way under biological condition. In conclusion, we found miR-490-3p could silence CDK1 to inhibit the proliferation of CC cells in an LLPS-depend manner.
Neutrophil Extracellular Traps: A Perspective of Neuroinflammation and Complement Activation in Alzheimer’s Disease
Authors: Kretzschmar Gabriela Canalli , Bumiller-Bini Valéria , Gasparetto Filho Miguel Angelo , Zonta Yohan Ricci , Yu Kaio Shu Tsyr , de Souza Ricardo Lehtonen R. , Dias-Melicio Luciane Alarcão , Boldt Angelica Beate Winter
Published: April 2021

Complement system (CS) components are associated with Alzheimer’s disease (AD), the commonest cause of dementia in the world. Neutrophils can be attracted to amyloid-β plaques by several pro-inflammatory factors, including the complement anaphylatoxin C5a. They may release neutrophil extracellular traps (NETs), which are chromatin nets associated with myeloperoxidase, elastase, and other enzymes. Some CS molecules, such as C5a, C1q, and CR1, are associated with increased neutrophil recruitment and NETs release. However, the relationship between CS molecules and NETs in AD is poorly understood. In this work, we detected higher NET concentrations in plasma and serum of Brazilian AD patients, than in elderly controls (medians = 2.78 [2.07–6.19] vs. 2.23 [0.33–4.14] ng/mL,p= 0.0005). We discussed these results within the context of our former findings on complement and AD and the context of the literature on complement and NET release, suggesting both as possible therapeutic targets to prevent the progress of the disease.
A Deep Learning Approach for Automatic Seizure Detection in Children With Epilepsy
Authors: Abdelhameed Ahmed , Bayoumi Magdy
Published: April 2021

Over the last few decades, electroencephalogram (EEG) has become one of the most vital tools used by physicians to diagnose several neurological disorders of the human brain and, in particular, to detect seizures. Because of its peculiar nature, the consequent impact of epileptic seizures on the quality of life of patients made the precise diagnosis of epilepsy extremely essential. Therefore, this article proposes a novel deep-learning approach for detecting seizures in pediatric patients based on the classification of raw multichannel EEG signal recordings that are minimally pre-processed. The new approach takes advantage of the automatic feature learning capabilities of a two-dimensional deep convolution autoencoder (2D-DCAE) linked to a neural network-based classifier to form a unified system that is trained in a supervised way to achieve the best classification accuracy between the ictal and interictal brain state signals. For testing and evaluating our approach, two models were designed and assessed using three different EEG data segment lengths and a 10-fold cross-validation scheme. Based on five evaluation metrics, the best performing model was a supervised deep convolutional autoencoder (SDCAE) model that uses a bidirectional long short-term memory (Bi-LSTM) – based classifier, and EEG segment length of 4 s. Using the public dataset collected from the Children’s Hospital Boston (CHB) and the Massachusetts Institute of Technology (MIT), this model has obtained 98.79 ± 0.53% accuracy, 98.72 ± 0.77% sensitivity, 98.86 ± 0.53% specificity, 98.86 ± 0.53% precision, and an F1-score of 98.79 ± 0.53%, respectively. Based on these results, our new approach was able to present one of the most effective seizure detection methods compared to other existing state-of-the-art methods applied to the same dataset.
Bilateral Vertebral Artery Hypoplasia and Fetal-Type Variants of the Posterior Cerebral Artery in Acute Ischemic Stroke
Authors: Hsu Chung-Fu , Chen Kuan-Wen , Su Chun-Hung , Shen Chao-Yu , Chi Hsin-Yi
Published: April 2021

Aim: Unilateral vertebral artery hypoplasia is considered a risk factor for posterior circulation infarction. Despite the increasing attention on unilateral vertebral artery hypoplasia, few studies have discussed bilateral vertebral artery hypoplasia, its influence on stroke, or its collateral supply from the circle of Willis. We aimed to identify its characteristics, stroke pattern, and unique ultrasonographic and brain imaging findings.

Materials and Methods: Of the 1,301 consecutive in-patients diagnosed with acute ischemic stroke from January 2013 to December 2015, medical and laboratory data and stroke or transient ischemic attack history were recorded. We enrolled patients who underwent both brain magnetic resonance imaging and sonography examinations. Vertebral artery and posterior cerebral artery analyses were conducted in accordance with clinical criteria.

Results: Adequate imaging data were available for 467 patients. Of these, eight patients met the criteria for bilateral vertebral artery hypoplasia. The mean age was 62.9 ± 12.1 years. There were six male (75.0%) and two female patients (25.0%). A high prevalence of hypertension (7/8, 87.5%) was noted.

Sonograms displayed a very low net flow volume in the vertebral arteries, with the average net flow volume being 28.9 ± 9.7 mL/min. A high frequency (6/8; 75.0%) of the fetal variant posterior cerebral artery from the carotids was found. The infarction patterns in these patients were all bilateral, scattered, and in multiple vascular territories.

Conclusion: Patients with bilateral vertebral hypoplasia displayed a unique collateral supply, special stroke pattern, and younger stroke onset. Early recognition and stroke prevention should be considered critical in clinical practice.
Predictors of Function, Activity, and Participation of Stroke Patients Undergoing Intensive Rehabilitation: A Multicenter Prospective Observational Study Protocol
Authors: Hakiki Bahia , Paperini Anita , Castagnoli Chiara , Hochleitner Ines , Verdesca Sonia , Grippo Antonello , Scarpino Maenia , Maiorelli Antonio , Mosca Irene Eleonora , Gemignani Paola , Borsotti Marco , Gabrielli Maria Assunta , Salvadori Emilia , Poggesi Anna , Lucidi Giulia , Falsini Catiuscia , Gentilini Monica , Martini Monica , Luisi Maria Luisa Eliana , Biffi Barbara , Mainardi Paolo , Barretta Teresa , Pancani Silvia , Mannini Andrea , Campagnini Silvia , Bagnoli Silvia , Ingannato Assunta , Nacmias Benedetta , Macchi Claudio , Carrozza Maria Chiara , Cecchi Francesca
Published: April 2021

Background: The complex nature of stroke sequelae, the heterogeneity in rehabilitation pathways, and the lack of validated prediction models of rehabilitation outcomes challenge stroke rehabilitation quality assessment and clinical research. An integrated care pathway (ICP), defining a reproducible rehabilitation assessment and process, may provide a structured frame within investigated outcomes and individual predictors of response to treatment, including neurophysiological and neurogenetic biomarkers. Predictors may differ for different interventions, suggesting clues to personalize and optimize rehabilitation. To date, a large representative Italian cohort study focusing on individual variability of response to an evidence-based ICP is lacking, and predictors of individual response to rehabilitation are largely unexplored. This paper describes a multicenter study protocol to prospectively investigate outcomes and predictors of response to an evidence-based ICP in a large Italian cohort of stroke survivors undergoing post-acute inpatient rehabilitation.

Methods: All patients with diagnosis of ischemic or hemorrhagic stroke confirmed both by clinical and brain imaging evaluation, admitted to four intensive rehabilitation units (adopting the same stroke rehabilitation ICP) within 30 days from the acute event, aged 18+, and providing informed consent will be enrolled (expected sample: 270 patients). Measures will be taken at admission (T0), at discharge (T1), and at follow-up 6 months after a stroke (T2), including clinical data, nutritional, functional, neurological, and neuropsychological measures, electroencephalography and motor evoked potentials, and analysis of neurogenetic biomarkers.

Statistics: In addition to classical multivariate logistic regression analysis, advanced machine learning algorithms will be cross-validated to achieve data-driven prognosis prediction models.

Discussion: By identifying data-driven prognosis prediction models in stroke rehabilitation, this study might contribute to the development of patient-oriented therapy and to optimize rehabilitation outcomes.

Clinical Trial Registration:ClinicalTrials.gov, NCT03968627. https://www.clinicaltrials.gov/ct2/show/NCT03968627?term=Cecchi&cond=Stroke&draw=2&rank=2.
Alternating Hemiplegia of Childhood: Genotype–Phenotype Correlations in a Cohort of 39 Italian Patients
Authors: Cordani Ramona , Stagnaro Michela , Pisciotta Livia , Tiziano Francesco Danilo , Calevo Maria Grazia , Nobili Lino ,   I.B.AHC Consortium, De Grandis Elisa
Published: April 2021

Alternating hemiplegia of childhood is a rare neurological disease characterized by paroxysmal movement disorders and chronic neurological disturbances, with onset before 18 months of age. Mutations in theATP1A3gene have been identified in up to 80% of patients. Thirty-nine patients [20 females, 19 males, mean age 25.32 years (7.52–49.34)] have been recruited through the Italian Biobank and Clinical Registry for Alternating Hemiplegia of Childhood. Demographic data, genotype, paroxysmal movement disorders, chronic neurological features, and response to flunarizine have been analyzed.ATP1A3gene mutations have been detected in 92.3% of patients. Patients have been divided into three groups—p.Asp801Asn mutation patients (26%), p.Glu815Lys cases (23%), and patients with otherATP1A3mutations—and statistically compared. The Italian cohort has a higher percentage ofATP1A3gene mutation than reported in literature (92.3%). Our data confirm a more severe phenotype in patients with p.Glu815Lys mutation, with an earlier age of onset of plegic (p= 0.02 in the correlation with other mutations) and tonic attacks. P.Glu815Lys patients most frequently present altered muscle tone, inability to walk (p= 0.01 comparing p.Glu815Lys and p.Asp801Asn mutations), epilepsy, and a more severe grade of dystonia (p< 0.05 comparing p.Glu815Lys and p.Asp801Asn mutations). They have moderate/severe intellectual disability and severe language impairment (p< 0.05). Interestingly, flunarizine seems to be more efficacious in patients with p.Glu815Lys mutation than p.Asp801Asn. In conclusion, our research suggests a genotype–phenotype correlation and provides information on this disorder's features, clinical course, and treatment.
Statistical Analysis of Graph-Theoretic Indices to Study EEG-TMS Connectivity in Patients With Depression
Authors: Olejarczyk Elzbieta , Jozwik Adam , Valiulis Vladas , Dapsys Kastytis , Gerulskis Giedrius , Germanavicius Arunas
Published: April 2021

Aim

The objective of this work was to demonstrate the usefulness of a novel statistical method to study the impact of transcranial magnetic stimulation (TMS) on brain connectivity in patients with depression using different stimulation protocols, i.e., 1 Hz repetitive TMS over the right dorsolateral prefrontal cortex (DLPFC) (protocol G1), 10 Hz repetitive TMS over the left DLPFC (G2), and intermittent theta burst stimulation (iTBS) consisting of three 50 Hz burst bundle repeated at 5 Hz frequency (G3).

Methods

Electroencephalography (EEG) connectivity analysis was performed using Directed Transfer Function (DTF) and a set of 21 indices based on graph theory. The statistical analysis of graph-theoretic indices consisted of a combination of thek-NN rule, the leave-one-out method, and a statistical test using a 2 × 2 contingency table.

Results

Our new statistical approach allowed for selection of the best set of graph-based indices derived from DTF, and for differentiation between conditions (i.e., before and after TMS) and between TMS protocols. The effects of TMS was found to differ based on frequency band.

Conclusion

A set of four brain asymmetry measures were particularly useful to study protocol- and frequency-dependent effects of TMS on brain connectivity.

Significance

The new approach would allow for better evaluation of the therapeutic effects of TMS and choice of the most appropriate stimulation protocol.