bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pedagogical Competence in Developing Assessment Instruments of Physics High School Teachers in Merauke District
Authors: Sari Desy Kumala , Budiman Nur Arip , Dinata Pri Ariadi Cahya , Bahri Syamsul
Published: June 2021

This study aims to map the ability to develop assessment instruments owned by physics teachers, especially in the Merauke district. The method used in this research is descriptive quantitative. Respondents who were involved in this study were 14 respondents who were physics teachers in Merauke. The data collection instrument used was a questionnaire containing 25 statements. The data of the research results were analyzed using the Ideal Standard Deviation. Overall, physics teachers’ competence in constructing and analyzing items is in the “good” category, with an average of 90.5. However, some assessment indicators need to be improved, such as reviewing objectives of constructing test instrument, content validation, revising based on validator’s suggestions, and analyzing the items.
CBX4 Provides an Alternate Mode of Colon Cancer Development via Potential Influences on Circadian Rhythm and Immune Infiltration
Authors: Wei Wangzhi , Zhao Wei , Zhang Yu
Published: June 2021

The circadian machinery is critical for the normal physiological functions and cellular processes. Circadian rhythm disruption has been associated with immune suppression which leads to higher cancer risk, suggesting a putative tumor protective role of circadian clock homeostasis. CBX4, as an epigenetic regulator, has been explored for its involvement in tumorigenesis. However, little is known about the correlation between CBX4 and circadian rhythm disruption in colon cancer as well as the potential impact on the tumor immunity. A significant upregulation of CBX4 was identified in the TCGA colon adenocarcinoma (COAD) samples when compared with the normal controls (p < 0.001). This differential expression was confirmed at the protein level using colon adenocarcinoma tissue array (p < 0.01). CBX4 was up-regulated in the recurred/progressed colon cancer cases compared with the disease-free samples (p < 0.01), suggesting CBX4 as a potential predictor for poor prognosis. With regard to nodular metastasis, CBX4 was found to be associated with early onset of metastatic diseases but not late progression. The circadian rhythm is orchestrated by the alternating activation and suppression of the CLOCK/ARNTL-driven positive loop and the PER/CRY-controlled negative loop. In COAD, CBX4 was negatively correlated with CLOCK (p < 0.001), and positively correlated with PER1 (p < 0.001), PER3 (p < 0.01), and CRY2 (p < 0.001) as well as NR1D1 (p < 0.001), a critical negative regulator of the circadian clock. These interactions consistently impacted on patient survival based on the colorectal cancer cohorts GSE17536 and GSE14333 of PrognoScan. CBX4 showed significant negative correlations with infiltrating B cells (p < 0.05) and CD4+ T cells (p < 0.01), and positive correlations with myeloid derived suppressor cells (MDSCs) (p < 0.05) and cancer associated fibroblast (CAFs) (p < 0.001), as well as a low immunoscore. Moreover, CBX4 displayed significant correlations with diverse immune metagenes. PER1 and PER3, consistent with their coordinated expression with CBX4, also had strong correlations with these gene representatives in COAD, suggesting a potential interaction of CBX4 with the circadian machinery. Our studies implicate that CBX4 may contribute to colon cancer development via potential influence on circadian rhythm and immune infiltration. These findings provide new insights into deciphering the function of CBX4, and may contribute to the development of new targeting strategies.
Identification and Validation of a Novel Prognosis Prediction Model in Adrenocortical Carcinoma by Integrative Bioinformatics Analysis, Statistics, and Machine Learning
Authors: Yan Xin , Guo Zi-Xin , Yu Dong-Hu , Chen Chen , Liu Xiao-Ping , Yang Zhi-Wei , Liu Tong-Zu , Li Sheng
Published: June 2021

Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. Thus, we aimed to establish a potential gene model for prognosis prediction of patients with ACC. First, weighted gene co-expression network (WGCNA) was constructed to screen two key modules (blue: P = 5e-05, R^2 = 0.65; red: P = 4e-06, R^2 = −0.71). Second, 93 survival-associated genes were identified. Third, 11 potential prognosis models were constructed, and two models were further selected. Survival analysis, receiver operating characteristic curve (ROC), Cox regression analysis, and calibrate curve were performed to identify the best model with great prognostic value. Model 2 was further identified as the best model [training set: P < 0.0001; the area under curve (AUC) value was higher than in any other models showed]. We further explored the prognostic values of genes in the best model by analyzing their mutations and copy number variations (CNVs) and found that MKI67 altered the most (12%). CNVs of the 14 genes could significantly affect the relative mRNA expression levels and were associated with survival of ACC patients. Three independent analyses indicated that all the 14 genes were significantly associated with the prognosis of patients with ACC. Six hub genes were further analyzed by constructing a PPI network and validated by AUC and concordance index (C-index) calculation. In summary, we constructed and validated a prognostic multi-gene model and found six prognostic biomarkers, which may be useful for predicting the prognosis of ACC patients.
CUL5–ASB6 Complex Promotes p62/SQSTM1 Ubiquitination and Degradation to Regulate Cell Proliferation and Autophagy
Authors: Gong Liyan , Wang Kaihua , Wang Mengcheng , Hu Ronggui , Li Huaguang , Gao Daming , Lin Moubin
Published: June 2021

p62/SQSTM1 (sequestosome-1) is a key protein involved in multiple cellular bioprocesses including autophagy, nutrient sensing, cell growth, cell death, and survival. Therefore, it is implicated in human diseases such as obesity and cancer. Here, we show that the CUL5–ASB6 complex is a ubiquitin E3 ligase complex mediating p62 ubiquitination and degradation. Depletion of CUL5 or ASB6 induced p62 accumulation, and overexpression of ASB6 promoted ubiquitination and degradation of p62. Functionally, ASB6 overexpression can inhibit the proliferation of MEF and hepatocellular carcinoma cells by reducing p62 protein level, and impair the occurrence of autophagy. Overall, our study identified a new molecular mechanism regulating p62 stability, which may provide additional insights for understanding the delicate control of p62 and cell proliferation–autophagy control in physiological and pathological settings.
Synthesis of Low Cost Titanium Silicalite-1 Zeolite for Highly Efficient Propylene Epoxidation
Authors: Liu Meng , Huang Zihan , Wei Wei , Wang Xiangyu , Wen Yiqiang
Published: June 2021

Developing an effective and low-cost system to synthesize titanium silicalite-1 (TS-1) zeolite is desirable for a range of industrial applications. To date, the poor catalytic activity of the synthesized zeolite due to the low amount of framework titanium and large crystal size is the main obstacle limiting the widespread application of this material. Moreover, a large amount of wastewater is often produced by the existing synthesis process. Herein, a green and sustainable route for synthesizing small-crystal TS-1 with a high fraction of framework Ti was demonstrated via a seed-assisted method using a tetrapropylammonium bromide (TPABr)-ethanolamine hydrothermal system. The influence of the synthesis conditions on the physicochemical properties and catalytic activities of TS-1 was investigated. With the assistance of nanosized S-1 seeds, the incorporation of Ti into the framework of TS-1 was promoted, and the crystallization rate was effectively accelerated. After alkaline etching, the obtained hierarchical TS-1 had higher catalytic activity towards propylene epoxidation with an extremely high turnover frequency of 1,650 h−1. Furthermore, the mother liquid during the hydrothermal reaction could be reused for the next synthesis procedure. Consequently, utilization ratios of both ethanolamine and TPABr exceeding 95% were achieved by recycling the mother liquid. This low-cost approach for reducing wastewater could be easily scaled up to provide a promising synthesis method for the industrial production of TS-1 and other topological zeolites.
The Third Dimension. On the Dichotomy Between Speech and Writing
Authors: Tomasin Lorenzo
Published: June 2021

This paper introduces a more complex and refined articulated view than the classic and simple dichotomy of linguistic production. According to the traditional doxa, what is linguistically articulated is either spoken or written. Forms of written language have previously been considered a secondary representation of spoken forms and, at least in the alphabetic system, the only properly linguistic form. I argue that there exists a third dimension of language, which is internal. This internal form is lexically, phonetically and grammatically articulated, without being spoken in a proper sense, but which can be seen as the pre-condition for both spoken and written production. In other words, linguistic production does not necessarily imply the presence of two interacting speakers (or writers/readers). Production can be seen as the simple effect of an internal activity, and can be described without reduction to spoken or written forms. A consideration of this third dimension in a systematic way could enrich and strengthen approaches to many types of texts and help to productively integrate the traditional schemes adopted in Sociolinguistics, Historical Linguistics, Philology, Literary Criticism, and Pragmatics.
Factors Influencing People's Response Toward Tiger Translocation in Satkosia Tiger Reserve, Eastern India
Authors: Vasudeva Vaishali , Ramasamy Pitchai , Pal Rabi Sankar , Behera Gatikrishna , Karat Pradeep Raj , Krishnamurthy Ramesh
Published: June 2021

Local communities are an important stakeholder in any carnivore translocation programme and therefore, their acceptance of the translocation and support are essential to ensure its viability. Recent tiger augmentation efforts in Satkosia Tiger Reserve, India received mixed responses from the local communities, causing a stalemate in its progress. As a part of the adaptive management strategy, it was required to assess the concerns and issues to provide a practical solution. Hence, we analyzed the attitude of the people toward conservation in general and tiger specifically. We used structured questionnaire surveys and interviewed 1,932 households from 43 villages located in and around the reserve. We tested the influence of several variables representing four categories- (1) socio-economic, (2) ecosystem values and dependence, (3) relationship with the forest department and (4) losses and fear, on the attitude toward tiger conservation. The villages were clustered based on the responses received under these categories. While conserving forest was important to 91% of respondents, 71% of respondents supported wildlife conservation and only 35% felt important to conserve tiger. The logistic binary regression predicted that at the household level attitude toward tiger conservation is influenced positively by economic well-being, sense of forest ecosystem services, resource dependence and negatively influenced by restrictions from the forest department, and previous experience of loss due to wildlife. At the village level, literacy, resource dependence, access to clean cooking fuel and cooperation from the forest department predicted a positive attitude toward tiger conservation. Restriction from the forest department, fear for livestock, and experience of losses due to wildlife had a negative influence on attitude. We recommend that the villages in the landscape are prioritized based on their needs and accordingly, specific interventions are made to address their concerns. Future augmentation programme must give importance to intangible factors such as fear and perceived restrictions and opt for the involvement of the local community in the decision-making process.
E-Learning System Use During Emergency: An Empirical Study During the COVID-19 Pandemic
Authors: Alyoussef Ibrahim
Published: June 2021

The pandemic of COVID-19 quickly led to the closure of universities and colleges around the world, hoping that the guidance of social distancing from public health authorities will help flatten the curve of infection and minimize the overall fatalities from the epidemic. The e-learning framework, however, is the best solution to enable students to learn about the quality of education. The aim of this research was to examine variables reflecting the actual use of the e-learning system during the COVID-19 pandemic among university students. The perceived ease of use and perceived usefulness are positively correlated with facilitating condition, perceived control, and self-efficacy, which in turn influences students’ attitude toward use, which in turn affects the actual use of the e-learning system during the COVID-19 pandemic. To exam the model on the basis of user data from the e-learning system used collected through an online survey, structural equation modeling (SEM) and path analysis were used. The findings showed that the mindset of students to use had positive effects on the learning of students during the COVID-19 pandemic through the actual use of the e-learning system. In the context of e-learning programs in developing countries, previous studies have seldom explored an integrated model. In addition, this article aims to include a literature review of recently published research on the actual use of the e-learning system during the pandemic of COVID-19.
Evaluating Assisted Gene Flow in Marginal Populations of a High Mountain Species
Authors: Prieto-Benítez Samuel , Morente-López Javier , Rubio Teso María Luisa , Lara-Romero Carlos , García-Fernández Alfredo , Torres Elena , Iriondo José María
Published: June 2021

Many species cannot either migrate or adapt at the rate of temperature increases due to climate warming. Therefore, they need active conservation strategies to avoid extinction. Facilitated adaptation actions, such assisted gene flow, aim at the increase of the evolutionary resilience of species affected by global change. In elevational gradients, marginal populations at the lower elevation edges are experiencing earlier snowmelt and higher temperatures, which force them to adapt to the new conditions by modifying their phenology. In this context, advancing the onset of flowering and seed germination times are crucial to ensure reproductive success and increase seedling survival prior to summer drought. Assisted gene flow may bring adaptive alleles and increase genetic diversity that can help throughout ontogeny. The main aim of this work is to assess the effects that different gene flow treatments could have on the desired trait changes in marginal populations. Accordingly, we established a common garden experiment in which we assayed four different gene flow treatments betweenSilene ciliataPourr. (Caryophyllaceae) populations located in similar and different elevation edges, belonging to the same and different mountains. As a control treatment, within-population crosses of low elevation edge populations were performed. The resulting seeds were sown and the germination and flowering onset dates of the resulting plants recorded, as well as the seedling survival. Gene flow between populations falling on the same mountain and same elevation and gene flow from high-elevation populations from a different mountain to low-elevation populations advanced seed germination time with respect to control crosses. No significant effects of gene flow on seedling survival were found. All the gene flow treatments delayed the onset of flowering with respect to control crosses and this effect was more pronounced in among-mountain gene flows. The results of this study highlight two important issues that should be thoroughly studied before attempting to apply assisted gene flow in practical conservation situations. Firstly, among-populations gene flow can trigger different responses in crucial traits throughout the ontogeny of plant species. Secondly, the population provenance of gene flow is determinant and plays a significant role on the effects of gene flow.
A Potential Role for Integrin-Linked Kinase in Colorectal Cancer Growth and Progression via Regulating Senescence and Immunity
Authors: Almasabi Saleh , Ahmed Afsar U. , Boyd Richard , Williams Bryan R. G.
Published: June 2021

Integrin-linked kinase (ILK) has been implicated as a molecular driver and mediator in both inflammation and tumorigenesis of the colon. ILK functions as an adaptor and mediator protein linking the extracellular matrix with downstream signaling pathways. ILK is broadly expressed in many human tissues and cells. It is also overexpressed in many cancers, including colorectal cancer (CRC). Inflammation, as evidenced by inflammatory bowel disease (IBD), is one of the highest risk factors for initiating CRC. This has led to the hypothesis that targeting ILK therapeutically could have potential in CRC, as it regulates different cellular processes associated with CRC development and progression as well as inflammation in the colon. A number of studies have indicated an ILK function in senescence, a cellular process that arrests the cell cycle while maintaining active metabolism and transcription. Senescent cells produce different secretions collectively known as the senescence-associated secretory phenotype (SASP). The SASP secretions influence infiltration of different immune cells, either positively for clearing senescent cells or negatively for promoting tumor growth, reflecting the dual role of senescence in cancer. However, a role for ILK in senescence and immunity in CRC remains to be determined. In this review, we discuss the possible role for ILK in senescence and immunity, paying particular attention to the relevance of ILK in CRC. We also examine how activating Toll-like receptors (TLRs) and their agonists in CRC could trigger immune responses against cancer, as a combination therapy with ILK inhibition.
Novel Isoquinoline Alkaloid Litcubanine A - A Potential Anti-Inflammatory Candidate
Authors: Xia Huan , Liu Yitong , Xia Guiyang , Liu Yi , Lin Sheng , Guo Lijia
Published: June 2021

Macrophages play a critical role in innate and adaptive immunity, and the regulation of macrophage function in inflammatory disease treatment has been widely studied. Litsea cubeba is an important Chinese medicinal plant used for the treatment of inflammatory diseases. However, the inflammatory bioactive ingredients in L. cubeba and underlying molecular mechanisms are poorly understood. Herein, we first obtained and elucidated a novel isoquinoline alkaloid, Litcubanine A (LA), from L. cubeba. An in vitro study indicated that LA could significantly inhibit LPS-induced activation of inflammatory macrophages via the NF-κB pathway, leading to the decrease of inflammatory factors including iNOS, TNF-α, and IL-1β. Moreover, LA showed an inhibiting effect on the expression of NO in macrophages by directly binding to iNOS protein. Molecular simulation docking also demonstrated that active LA created an interaction with GLU 371 residue of iNOS via attractive charge derived from the N→O group, revealing its highly selective inhibition toward iNOS. By using the IκK inhibitor and iNOS inhibitor, these two regulatory targets of LA on inflammatory macrophages were verified in vitro. Finally, by using a caudal fin resection model in zebrafish larvae, and the skin wound healing model in mice, we proved in vivo that LA down-regulated the secretion of local inflammatory factors by inhibiting macrophage recruitment and activation at the early stage of the injury. Collectively, our study demonstrated that the novel isoquinoline alkaloid LA suppresses LPS-induced activation of inflammatory macrophages by modulating the NF-κB pathway, suggesting that inflammatory macrophage activation pathway is an effective target for inflammation treatment, and LA is a new pharmacophore for the development of novel and effective anti-inflammatory agents to regulate local macrophages.
Patterns of Research Effort and Extinction Risk of Marine Mammals in the Philippines
Authors: Tiongson Angelico Jose C. , Utzurrum Jean Asuncion , de la Paz Manuel Eduardo L.
Published: June 2021

Global marine mammal research is disproportionately lacking compared to terrestrial mammal research and is strongly biased toward populations in Europe, North America, New Zealand, and Australia. With high extinction risks facing marine mammals in the tropics, we sought to identify potential drivers of research effort and extinction risk evaluations for marine mammals in the Philippines as a model for tropical island nations with limited resources and research capacity. Using a bibliographic approach, we compiled all materials on marine mammal research in the Philippines from 1991 to 2020, which we categorized into eight thematic areas of research focus. We reviewed all materials based on their research focus to assess the current scientific knowledge of local marine mammal populations. Using a simple metric to calculate research effort allocation, we found that all marine mammal species in the Philippines receive inadequate research attention. Using generalized linear models, we analyzed the relationship of potential factors that drive research effort. The model with the lowest Akaike Information Criterion value suggests that frequency of marine mammal stranding incidents may influence an increase in research effort on marine mammals by providing access to biological specimens that would normally be difficult to obtain. Strandings are unfortunate events with often unclear causes, but they provide an opportunity to collect data from behaviorally cryptic animals in areas where financial constraints often hamper scientific progress. We also determined that a national Red List evaluation was predicted by increased research effort. Maximizing local research using all materials from strandings and building research capacity may be an alternative to expensive field-based methods to increase knowledge on local marine mammal populations.
Frailty and Geriatric Medicine During the Pandemic
Authors: Crosignani Silvia , Fantinati Jacopo , Cesari Matteo
Published: June 2021

The term frailty in the era of coronavirus disease 2019 (COVID-19) has a manifold implication. The vast majority of the countries worldwide being hit by the pandemic have shown the frailty of their health and social care systems. Although the surprise factor could somehow justify the unpreparedness experienced during the first wave, the second wave still led to significant difficulties almost everywhere. Looking at Italy's situation, it is evident how the stress test applied by COVID-19 on the system has threatened its stability, getting it closer to collapsing many times. It is true that Italy, in particular the Northern regions, has been the epicenter of COVID-19 in Europe in a time when information about the severe acute respiratory syndrome coronavirus 2 was still lacking and confusing. Nevertheless, what happened has demonstrated significant issues in the structure, priorities, and organization of the system. It has exemplified the obsolete approach adopted in clinical practice, particularly when applied to frail older persons. The COVID-19 pandemic has made emerging the need for a substantial reshaping of our healthcare system. The hospital-centered model has dramatically failed. To adequately face the new challenges brought by the increasing complexity of our aging society, it is critical to move the barycenter of action toward the community/primary care, promoting the integration of services and centralization of clinical/administrative data. It is vital to train healthcare professionals in the identification and basic principles of geriatric conditions, clarifying the role that geriatricians play. In the present article, some cornerstone concepts of geriatric medicine (i.e., definition of geriatrics, multidisciplinarity, integrated care, and development of clinical databases for filling the evidence-based medicine gaps) are presented, explaining the challenges they have faced during the COVID-19 pandemic and possible solutions for implementing improvements in the future.
A Metagenomic Insight Into the Hindgut Microbiota and Their Metabolites for Dairy Goats Fed Different Rumen Degradable Starch
Authors: Han Xiaoying , Lei Xinjian , Yang Xuexin , Shen Jing , Zheng Lixin , Jin Chunjia , Cao Yangchun , Yao Junhu
Published: June 2021

High starch diets have been proven to increase the risk of hindgut acidosis in high-yielding dairy animals. As an effective measurement of dietary carbohydrate for ruminants, studies on rumen degradable starch (RDS) and the effects on the gut microbiota diversity of carbohydrate-active enzymes (CAZymes), and Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology functional categories are helpful to understand the mechanisms between gut microbiota and carbohydrate metabolism in dairy goats. A total of 18 lactating goats (45.8 ± 1.54 kg) were randomly divided equally into three dietary treatments with low dietary RDS concentrations of 20.52% (LRDS), medium RDS of 22.15% (MRDS), and high RDS of 24.88% (HRDS) on a DM basis for 5 weeks. Compared with the LRDS and MRDS groups, HRDS increased acetate molar proportion in the cecum. For the HRDS group, the abundance of family Ruminococcaceae and genus Ruminococcaceae UCG-010 were significantly increased in the cecum. For the LRDS group, the butyrate molar proportion and the abundance of butyrate producer family Bacteroidale_S24-7, family Lachnospiraceae, and genus Bacteroidale_S24-7_group were significantly increased in the cecum. Based on the BugBase phenotypic prediction, the microbial oxidative stress tolerant and decreased potentially pathogenic in the LRDS group were increased in the cecum compared with the HRDS group. A metagenomic study on cecal bacteria revealed that dietary RDS level could affect carbohydrate metabolism by increasing the glycoside hydrolase 95 (GH95) family and cellulase enzyme (EC 3.2.1.4) in the HRDS group; increasing the GH13_20 family and isoamylase enzyme (EC 3.2.1.68) in the LRDS group. PROBIO probiotics database showed the relative gene abundance of cecal probiotics significantly decreased in the HRDS group. Furthermore, goats fed the HRDS diet had a lower protein expression of Muc2, and greater expression RNA of interleukin-1β and secretory immunoglobulin A in cecal mucosa than did goats fed the LRDS diet. Combined with the information from previous results from rumen, dietary RDS level altered the degradation position of carbohydrates in the gastrointestinal (GI) tract and increased the relative abundance of gene encoded enzymes degrading cellulose in the HRDS group in the cecum of dairy goats. This study revealed that the HRDS diet could bring disturbances to the microbial communities network containing taxa of the Lachnospiraceae and Ruminococcaceae and damage the mucus layer and inflammation in the cecum of dairy goats.
Multifaceted Roles of ICP22/ORF63 Proteins in the Life Cycle of Human Herpesviruses
Authors: Wu Ying , Yang Qiqi , Wang Mingshu , Chen Shun , Jia Renyong , Yang Qiao , Zhu Dekang , Liu Mafeng , Zhao Xinxin , Zhang Shaqiu , Huang Juan , Ou Xumin , Mao Sai , Gao Qun , Sun Di , Tian Bin , Cheng Anchun
Published: June 2021

Herpesviruses are extremely successful parasites that have evolved over millions of years to develop a variety of mechanisms to coexist with their hosts and to maintain host-to-host transmission and lifelong infection by regulating their life cycles. The life cycle of herpesviruses consists of two phases: lytic infection and latent infection. During lytic infection, active replication and the production of numerous progeny virions occur. Subsequent suppression of the host immune response leads to a lifetime latent infection of the host. During latent infection, the viral genome remains in an inactive state in the host cell to avoid host immune surveillance, but the virus can be reactivated and reenter the lytic cycle. The balance between these two phases of the herpesvirus life cycle is controlled by broad interactions among numerous viral and cellular factors. ICP22/ORF63 proteins are among these factors and are involved in transcription, nuclear budding, latency establishment, and reactivation. In this review, we summarized the various roles and complex mechanisms by which ICP22/ORF63 proteins regulate the life cycle of human herpesviruses and the complex relationships among host and viral factors. Elucidating the role and mechanism of ICP22/ORF63 in virus–host interactions will deepen our understanding of the viral life cycle. In addition, it will also help us to understand the pathogenesis of herpesvirus infections and provide new strategies for combating these infections.
Characterization of Bacterial Community Dynamics of the Human Mouth Throughout Decomposition via Metagenomic, Metatranscriptomic, and Culturing Techniques
Authors: Ashe Emily C. , Comeau André M. , Zejdlik Katie , O’Connell Seán P.
Published: June 2021

The postmortem microbiome has recently moved to the forefront of forensic research, and many studies have focused on the idea that predictable fluctuations in decomposer communities could be used as a “microbial clock” to determine time of death. Commonly, the oral microbiome has been evaluated using 16S rRNA gene sequencing to assess the changes in community composition throughout decomposition. We sampled the hard palates of three human donors over time to identify the prominent members of the microbiome. This study combined 16S rRNA sequencing with whole metagenomic (MetaG) and metatranscriptomic (MetaT) sequencing and culturing methodologies in an attempt to broaden current knowledge about how these postmortem microbiota change and might function throughout decomposition. In all four methods, Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes were the dominant phyla, but their distributions were insufficient in separating samples based on decomposition stage or time or by donor. Better resolution was observed at the level of genus, with fresher samples from decomposition clustering away from others via principal components analysis (PCA) of the sequencing data. Key genera in driving these trends included Rothia; Lysinibacillus, Lactobacillus, Staphylococcus, and other Firmicutes; and yeasts including Candida and Yarrowia. The majority of cultures (89%) matched to sequences obtained from at least one of the sequencing methods, while 11 cultures were found in the same samples using all three methods. These included Acinetobacter gerneri, Comamonas terrigena, Morganella morganii, Proteus vulgaris, Pseudomonas koreensis, Pseudomonas moraviensis, Raoutella terrigena, Stenotrophomonas maltophilia, Bacillus cereus, Kurthia zopfii, and Lactobacillus paracasei. MetaG and MetaT data also revealed many novel insects as likely visitors to the donors in this study, opening the door to investigating them as potential vectors of microorganisms during decomposition. The presence of cultures at specific time points in decomposition, including samples for which we have MetaT data, will yield future studies tying specific taxa to metabolic pathways involved in decomposition. Overall, we have shown that our 16S rRNA sequencing results from the human hard palate are consistent with other studies and have expanded on the range of taxa shown to be associated with human decomposition, including eukaryotes, based on additional sequencing technologies.
The Hsp70-Chaperone Machines in Bacteria
Authors: Mayer Matthias P.
Published: June 2021

The ATP-dependent Hsp70s are evolutionary conserved molecular chaperones that constitute central hubs of the cellular protein quality surveillance network. None of the other main chaperone families (Tig, GroELS, HtpG, IbpA/B, ClpB) have been assigned with a comparable range of functions. Through a multitude of functions Hsp70s are involved in many cellular control circuits for maintaining protein homeostasis and have been recognized as key factors for cell survival. Three mechanistic properties of Hsp70s are the basis for their high versatility. First, Hsp70s bind to short degenerate sequence motifs within their client proteins. Second, Hsp70 chaperones switch in a nucleotide-controlled manner between a state of low affinity for client proteins and a state of high affinity for clients. Third, Hsp70s are targeted to their clients by a large number of cochaperones of the J-domain protein (JDP) family and the lifetime of the Hsp70-client complex is regulated by nucleotide exchange factors (NEF). In this review I will discuss advances in the understanding of the molecular mechanism of the Hsp70 chaperone machinery focusing mostly on the bacterial Hsp70 DnaK and will compare the two other prokaryotic Hsp70s HscA and HscC with DnaK.
The Significance of EEG Alpha Oscillation Spectral Power and Beta Oscillation Phase Synchronization for Diagnosing Probable Alzheimer Disease
Authors: Zhang Haifeng , Geng Xinling , Wang Yuanyuan , Guo Yanjun , Gao Ya , Zhang Shouzi , Du Wenjin , Liu Lixin , Sun Mingyan , Jiao Fubin , Yi Fang , Li Xiaoli , Wang Luning
Published: June 2021

Alzheimer disease (AD) is the most common cause of dementia in geriatric population. At present, no effective treatments exist to reverse the progress of AD, however, early diagnosis and intervention might delay its progression. The search for biomarkers with good safety, repeatable detection, reliable sensitivity and community application is necessary for AD screening and early diagnosis and timely intervention. Electroencephalogram (EEG) examination is a non-invasive, quantitative, reproducible, and cost-effective technique which is suitable for screening large population for possible AD. The power spectrum, complexity and synchronization characteristics of EEG waveforms in AD patients have distinct deviation from normal elderly, indicating these EEG features can be a promising candidate biomarker of AD. However, current reported deviation results are inconsistent, possibly due to multiple factors such as diagnostic criteria, sample sizes and the use of different computational measures. In this study, we collected two neurological tests scores (MMSE and MoCA) and the resting-state EEG of 30 normal control elderly subjects (NC group) and 30 probable AD patients confirmed by Pittsburgh compound B positron emission tomography (PiB-PET) inspection (AD group). We calculated the power spectrum, spectral entropy and phase synchronization index features of these two groups’ EEG at left/right frontal, temporal, central and occipital brain regions in 4 frequency bands: δ oscillation (1–4 Hz), θ oscillation (4–8 Hz), α oscillation (8–13 Hz), and β oscillation (13–30 Hz). In most brain areas, we found that the AD group had significant differences compared to NC group: (1) decreased α oscillation power and increased θ oscillation power; (2) decreased spectral entropy in α oscillation and elevated spectral entropy in β oscillation; and (3) decrease phase synchronization index in δ, θ, and β oscillation. We also found that α oscillation spectral power and β oscillation phase synchronization index correlated well with the MMSE/MoCA test scores in AD groups. Our study suggests that these two EEG features might be useful metrics for population screening of probable AD patients.
Locus Coeruleus Norepinephrine in Learned Behavior: Anatomical Modularity and Spatiotemporal Integration in Targets
Authors: Breton-Provencher Vincent , Drummond Gabrielle T. , Sur Mriganka
Published: June 2021

The locus coeruleus (LC), a small brainstem nucleus, is the primary source of the neuromodulator norepinephrine (NE) in the brain. The LC receives input from widespread brain regions, and projects throughout the forebrain, brainstem, cerebellum, and spinal cord. LC neurons release NE to control arousal, but also in the context of a variety of sensory-motor and behavioral functions. Despite its brain-wide effects, much about the role of LC-NE in behavior and the circuits controlling LC activity is unknown. New evidence suggests that the modular input-output organization of the LC could enable transient, task-specific modulation of distinct brain regions. Future work must further assess whether this spatial modularity coincides with functional differences in LC-NE subpopulations acting at specific times, and how such spatiotemporal specificity might influence learned behaviors. Here, we summarize the state of the field and present new ideas on the role of LC-NE in learned behaviors.
The Impact of Post-contrast Acute Kidney Injury on In-hospital Mortality After Endovascular Thrombectomy in Patients With Acute Ischemic Stroke
Authors: Laible Mona , Jenetzky Ekkehart , Möhlenbruch Markus Alfred , Bendszus Martin , Ringleb Peter Arthur , Rizos Timolaos
Published: June 2021

Background and Purpose: Clinical outcome and mortality after endovascular thrombectomy (EVT) in patients with ischemic stroke are commonly assessed after 3 months. In patients with acute kidney injury (AKI), unfavorable results for 3-month mortality have been reported. However, data on the in-hospital mortality after EVT in this population are sparse. In the present study, we assessed whether AKI impacts in-hospital and 3-month mortality in patients undergoing EVT.

Materials and Methods: From a prospectively recruiting database, consecutive acute ischemic stroke patients receiving EVT between 2010 and 2018 due to acute large vessel occlusion were included. Post-contrast AKI (PC-AKI) was defined as an increase of baseline creatinine of ≥0.5 mg/dL or >25% within 48 h after the first measurement at admission. Adjusting for potential confounders, associations between PC-AKI and mortality after stroke were tested in univariate and multivariate logistic regression models.

Results: One thousand one hundred sixty-nine patients were included; 166 of them (14.2%) died during the acute hospital stay. Criteria for PC-AKI were met by 29 patients (2.5%). Presence of PC-AKI was associated with a significantly higher risk of in-hospital mortality in multivariate analysis [odds ratio (OR) = 2.87, 95% confidence interval (CI) = 1.16–7.13, p = 0.023]. Furthermore, factors associated with in-hospital mortality encompassed higher age (OR = 1.03, 95% CI = 1.01–1.04, p = 0.002), stroke severity (OR = 1.05, 95% CI = 1.03–1.08, p < 0.001), symptomatic intracerebral hemorrhage (OR = 3.20, 95% CI = 1.69–6.04, p < 0.001), posterior circulation stroke (OR = 2.85, 95% CI = 1.72–4.71, p < 0.001), and failed recanalization (OR = 2.00, 95% CI = 1.35–3.00, p = 0.001).

Conclusion: PC-AKI is rare after EVT but represents an important risk factor for in-hospital mortality and for mortality within 3 months after hospital discharge. Preventing PC-AKI after EVT may represent an important and potentially lifesaving effort in future daily clinical practice.
An Online Data Visualization Feedback Protocol for Motor Imagery-Based BCI Training
Authors: Duan Xu , Xie Songyun , Xie Xinzhou , Obermayer Klaus , Cui Yujie , Wang Zhenzhen
Published: June 2021

Brain–computer interface (BCI) has developed rapidly over the past two decades, mainly due to advancements in machine learning. Subjects must learn to modulate their brain activities to ensure a successful BCI. Feedback training is a practical approach to this learning process; however, the commonly used classifier-dependent approaches have inherent limitations such as the need for calibration and a lack of continuous feedback over long periods of time. This paper proposes an online data visualization feedback protocol that intuitively reflects the EEG distribution in Riemannian geometry in real time. Rather than learning a hyperplane, the Riemannian geometry formulation allows iterative learning of prototypical covariance matrices that are translated into visualized feedback through diffusion map process. Ten subjects were recruited for MI-BCI (motor imagery-BCI) training experiments. The subjects learned to modulate their sensorimotor rhythm to centralize the points within one category and to separate points belonging to different categories. The results show favorable overall training effects in terms of the class distinctiveness and EEG feature discriminancy over a 3-day training with 30% learners. A steadily increased class distinctiveness in the last three sessions suggests that the advanced training protocol is effective. The optimal frequency band was consistent during the 3-day training, and the difference between subjects with good or low MI-BCI performance could be clearly observed. We believe that the proposed feedback protocol has promising application prospect.
Utilizing the Switching Stochasticity of HfO2/TiOx-Based ReRAM Devices and the Concept of Multiple Device Synapses for the Classification of Overlapping and Noisy Patterns
Authors: Bengel Christopher , Cüppers Felix , Payvand Melika , Dittmann Regina , Waser Rainer , Hoffmann-Eifert Susanne , Menzel Stephan
Published: June 2021

With the arrival of the Internet of Things (IoT) and the challenges arising from Big Data, neuromorphic chip concepts are seen as key solutions for coping with the massive amount of unstructured data streams by moving the computation closer to the sensors, the so-called “edge computing.” Augmenting these chips with emerging memory technologies enables these edge devices with non-volatile and adaptive properties which are desirable for low power and online learning operations. However, an energy- and area-efficient realization of these systems requires disruptive hardware changes. Memristor-based solutions for these concepts are in the focus of research and industry due to their low-power and high-density online learning potential. Specifically, the filamentary-type valence change mechanism (VCM memories) have shown to be a promising candidate In consequence, physical models capturing a broad spectrum of experimentally observed features such as the pronounced cycle-to-cycle (c2c) and device-to-device (d2d) variability are required for accurate evaluation of the proposed concepts. In this study, we present an in-depth experimental analysis of d2d and c2c variability of filamentary-type bipolar switching HfO2/TiOx nano-sized crossbar devices and match the experimentally observed variabilities to our physically motivated JART VCM compact model. Based on this approach, we evaluate the concept of parallel operation of devices as a synapse both experimentally and theoretically. These parallel synapses form a synaptic array which is at the core of neuromorphic chips. We exploit the c2c variability of these devices for stochastic online learning which has shown to increase the effective bit precision of the devices. Finally, we demonstrate that stochastic switching features for a pattern classification task that can be employed in an online learning neural network.
Long-Term Overconsumption of Sugar Starting at Adolescence Produces Persistent Hyperactivity and Neurocognitive Deficits in Adulthood
Authors: Beecher Kate , Alvarez Cooper Ignatius , Wang Joshua , Walters Shaun B. , Chehrehasa Fatemeh , Bartlett Selena E. , Belmer Arnauld
Published: June 2021

Sugar has become embedded in modern food and beverages. This has led to overconsumption of sugar in children, adolescents, and adults, with more than 60 countries consuming more than four times (>100 g/person/day) the WHO recommendations (25 g/person/day). Recent evidence suggests that obesity and impulsivity from poor dietary habits leads to further overconsumption of processed food and beverages. The long-term effects on cognitive processes and hyperactivity from sugar overconsumption, beginning at adolescence are not known. Using a well-validated mouse model of sugar consumption, we found that long-term sugar consumption, at a level that significantly augments weight gain, elicits an abnormal hyperlocomotor response to novelty and alters both episodic and spatial memory. Our results are similar to those reported in attention deficit and hyperactivity disorders. The deficits in hippocampal-dependent learning and memory were accompanied by altered hippocampal neurogenesis, with an overall decrease in the proliferation and differentiation of newborn neurons within the dentate gyrus. This suggests that long-term overconsumption of sugar, as that which occurs in the Western Diet might contribute to an increased risk of developing persistent hyperactivity and neurocognitive deficits in adulthood.
The Interaction Between Fatty Acid Desaturase-2 (FADS2) rs174583 Genetic Variant and Dietary Quality Indices (DASH and MDS) Constructs Different Metabolic Phenotypes Among Obese Individuals
Authors: Khodarahmi Mahdieh , Nikniaz Leila , Abbasalizad Farhangi Mahdieh
Published: June 2021

Background and Aim: Genetic variation in fatty acid desaturases (FADS) has previously been linked to several diet-related diseases. We aimed to determine whether the FADS2 rs174583 variant interacts with the Dietary Approach to Stop Hypertension (DASH) score and Mediterranean dietary score (MDS) to influence cardio-metabolic risk factors among obese adults.

Methods: This cross-sectional study was performed among 347 apparently healthy obese adults (aged 20–50 years). Dietary quality indicator scores (DASH and MDS) were generated using a validated 147-item Food Frequency Questionnaire (FFQ). The FADS2 rs174583 variant was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The gene–diet interaction was analyzed by the ANCOVA multivariate interaction model.

Results: A significant interaction was observed between rs174583 and adherence to the DASH score in relation to serum triglyceride (TG) concentration among the female group (PInteraction = 0.046); CT-genotype carriers who were assigned to the second tertile of DASH compared with those in the first tertile had a lower TG level (P < 0.05). Another significant interaction was revealed between adherence to MDS score and rs174583 polymorphism on serum glucose levels (PInteraction = 0.044); the lowest mean of glucose level was observed in homozygous minor subjects (TT) in the third tertile of MDS, in comparison with other tertiles of this dietary index (P < 0.05). There was a similar significant interaction between DASH and rs174583 in relation to diastolic blood pressure (PInteraction = 0.038) among the male group. Additionally, a significant positive association was found between TT genotype and odds of having high TG both in the crude (OR, 3.21; 95% CI, 1.02–10.14) and adjusted (OR, 3.58; 95% CI, 1.07–11.97) models, taking into account different confounders.

Conclusion: Adherence to the dietary quality indicators (DASH and MDS) modified the relationship between FADS2 rs174583 polymorphism and cardio-metabolic risk factors in obese subjects. Prospective cohort studies are needed to confirm the results of our study.