bluuebunny/crossref_metadata_2025 huggingface dataset:
The Early Permian Bolosaurid Eudibamus cursoris: Earliest Reptile to Combine Parasagittal Stride and Digitigrade Posture During Quadrupedal and Bipedal Locomotion
Authors: Berman David S , Sumida Stuart S. , Henrici Amy C. , Scott Diane , Reisz Robert R. , Martens Thomas
Published: July 2021

A comprehensive description of the holotype skeleton is presented here for the first time of the lower Permian (Artinskian) reptile Eudibamus cursoris from the Bromacker locality of Germany since the brief description of the holotype in 2000. The holotype is essentially complete and is the only known bolosaurid represented by a well-preserved articulated skeleton. Included in the description here is a superbly preserved, partial, articulated second specimen of E. cursoris discovered at the same locality that includes a short portion of the vertebral column associated with the pelvis and right hindlimb. Descriptions of the holotype and new specimen add substantially to features of the skull and postcranium that not only confirm a bolosaurid assignment, but also add significantly to an already long list of structural features supporting an ability unique among Paleozoic vertebrates to reach relatively high bipedal and quadrupedal running speeds employing a parasagittal stride and digitigrade stance with the limbs held in a near vertical posture. Structural differences between the two specimens are restricted to the tarsi and are attributed to different ontogenetic stages of ossification, with the holotype representing a more juvenile individual, and the larger second specimen representing a more mature animal.
Floral Volatiles: A Promising Method to Access the Rare Nocturnal and Crepuscular Bees
Authors: Martínez-Martínez Carlos A. , Cordeiro Guaraci D. , Martins Herbeson O. J. , Kobal Renan O. A. C. , Milet-Pinheiro Paulo , Stanton Mariana A. , Franco Emanuella L. , Krug Cristiane , Mateus Sidnei , Schlindwein Clemens , Dötterl Stefan , Alves-dos-Santos Isabel
Published: July 2021

Crepuscular and/or nocturnal bees fly during the dusk, the dawn or part of the night. Due to their short foraging time and sampling bias toward diurnal bees, nocturnal bees are rarely collected and poorly studied. So far, they have been mostly sampled with light and Malaise traps. However, synthetic chemical compounds resembling floral volatiles were recently found to be a promising alternative to attract these bees. By reviewing available literature and collecting original data, we present information on the attraction and sampling of nocturnal bees with scent-baited traps. Bees were actively captured with entomological nets while approaching to filter papers moistened with distinct chemical compound, or passively caught in bottles with scent baits left during the night. So far, all data available are from the Neotropics. Nocturnal bees belonging to three genera, i.e., Ptiloglossa, Megalopta, and Megommation were attracted to at least ten different synthetic compounds and mixtures thereof, identified from bouquets of flowers with nocturnal anthesis. Aromatic compounds, such as 2-phenyletanol, eugenol and methyl salicylate, and the monoterpenoid eucalyptol were the most successful in attracting nocturnal bees. We highlight the effectiveness of olfactory methods to survey crepuscular and nocturnal bees using chemical compounds typically reported as floral scent constituents, and the possibility to record olfactory preferences of each bee species to specific compounds. We suggest to include this method in apifauna surveys in order to improve our current knowledge on the diversity of nocturnal bees in different ecosystems.
Decipering the Molecular Mechanism of ACE2 Regulating A549 Cells
Authors: Xiao Kun , Song Licheng , Bai Ying , Liu Pengfei , Liu Yuhong , Xie Fei , Xie Lixin
Published: July 2021

Angiotensin-converting enzyme 2 (ACE2) is an aminopeptidase that functions as a part of the renin-angiotensin system (RAS). The RAS pathway plays a crucial role in regulating the local blood flow within a tissue. As a consequence, the role of ACE2 in regulating vasculature properties has been widely appreciated. Additionally, ACE2 has also been reported to show anti-tumorigenic activity. However, the mechanistic basis of this function has remained largely unexplored. In the current study, using a lentivirus-based expression system in lung cancer cells (A549), we show that ACE2 overexpression reduces the viability and migratory potential of cancer cells, highlighting the robust anti-tumorigenic effects of ACE2 function. Moreover, a quantitative proteome-level comparison between ACE2 overexpressed (OE) and empty vector-controlled (NC) cells reveals a large number (227) of differentially expressed proteins (DEPs) that may have contributed to this phenomenon. Functional enrichment of these DEPs has uncovered that most of them perform binding activities and enzymatic reactions associated with metabolic pathways and various post-transcriptional gene expression regulatory mechanisms. Besides, cellular component analysis reveals that the DEPs function across a range of compartments within a cell with a relatively heterogeneous distribution. Our study, therefore, supports the previously established anti-tumorigenic effects of ACE2 overexpression in lung cancer cells. An analysis based on comprehensive, unbiased, and quantitative proteomics, we have provided a rigorous mechanistic explanation for its functions.
Effect of Temperature and Maternal Age on Recombination Rate in Cattle
Authors: Shen Botong , Freebern Ellen , Jiang Jicai , Maltecca Christian , Cole John B. , Liu George E. , Ma Li
Published: July 2021

Meiotic recombination is a fundamental biological process that facilitates meiotic division and promotes genetic diversity. Recombination is phenotypically plastic and affected by both intrinsic and extrinsic factors. The effect of maternal age on recombination rates has been characterized in a wide range of species, but the effect’s direction remains inconclusive. Additionally, the characterization of temperature effects on recombination has been limited to model organisms. Here we seek to comprehensively determine the impact of genetic and environmental factors on recombination rate in dairy cattle. Using a large cattle pedigree, we identified maternal recombination events within 305,545 three-generation families. By comparing recombination rate between parents of different ages, we found a quadratic trend between maternal age and recombination rate in cattle. In contrast to either an increasing or decreasing trend in humans, cattle recombination rate decreased with maternal age until 65 months and then increased afterward. Combining recombination data with temperature information from public databases, we found a positive correlation between environmental temperature during fetal development of offspring and recombination rate in female parents. Finally, we fitted a full recombination rate model on all related factors, including genetics, maternal age, and environmental temperatures. Based on the final model, we confirmed the effect of maternal age and environmental temperature during fetal development of offspring on recombination rate with an estimated heritability of 10% (SE = 0.03) in cattle. Collectively, we characterized the maternal age and temperature effects on recombination rate and suggested the adaptation of meiotic recombination to environmental stimuli in cattle. Our results provided first-hand information regarding the plastic nature of meiotic recombination in a mammalian species.
Analyzing Roles of NUSAP1 From Clinical, Molecular Mechanism and Immune Perspectives in Hepatocellular Carcinoma
Authors: Zhu Wenjie , Xu Jian , Chen Zehao , Jiang Jianxin
Published: July 2021

Hepatocellular carcinoma (HCC) is one of the most common carcinomas worldwide. Our study aims to analyze how NUSAP1 affects progression of HCC from clinical, molecular mechanism and immune perspectives. Firstly, we downloaded GSE62232, GSE102079, GSE112790, and GSE121248 gene expression profile datasets from GEO database. R studio was used to screen DEGs of each dataset, and 86 overlapping DEGs of the four datasets were screened at last. Then, CytoHubba plug-in in Cytoscape software was used to screen out NUSAP1 from the 86 DEGs. Subsequently, survival analysis, clinical correlation analysis, independent prognostic analysis, and GSEA enrichment analysis of NUSAP1 were analyzed using HCC patients from GSE76427 dataset, ICGC database, and TCGA database. The results revealed that HCC patients with higher expression level of NUSAP1 had a worse prognosis. NUSAP1 was an independent prognostic factor of HCC, and it may promote HCC progress by regulating cell cycle. To further elucidate its underlying molecular mechanism, we used cBioProtal online data analysis tool to screen all co-expression genes of NUSAP1 and used top 300 co-expression genes to accomplish KEGG and GO enrichment analysis; the results confirmed that NUSAP1 accelerated progression of HCC by regulating cell cycle. We continued to draw KEGG pathway map of cell cycle using co-expression genes enriched in cell cycle pathway by KEGG online tool. The map depicted that most of co-expression genes of NUSAP1 were located in S phase and G2/M phase of the cell cycle, and they could regulate the genes in G1 phase. To further understand the mechanism of cell cycle, we also did qRT-PCR, Western blot, and flow cytometry; the results showed that NUSAP1 was closely associated with CDK4, CDK6, and cyclinD1, which could regulate G1 to S phase transition. Besides, we also analyzed correlation between NUSAP1 and immune cells using HCC patients from GSE76427 dataset, ICGC database, and TCGA database. NUSAP1 was associated with some immune cells, and we speculated that NUSAP1 could also promote HCC progression by influencing T cell CD4 memory resting and macrophage M0 through some underlying mechanism.
The N6-Methyladenosine-Modified Pseudogene HSPA7 Correlates With the Tumor Microenvironment and Predicts the Response to Immune Checkpoint Therapy in Glioblastoma
Authors: Zhao Rongrong , Li Boyan , Zhang Shouji , He Zheng , Pan Ziwen , Guo Qindong , Qiu Wei , Qi Yanhua , Zhao Shulin , Wang Shaobo , Chen Zihang , Zhang Ping , Guo Xing , Xue Hao , Li Gang
Published: July 2021

Background

Glioblastoma (GBM), one of the most aggressive tumors of the brain, has no effective or sufficient therapies. Identifying robust biomarkers for the response to immune checkpoint blockade (ICB) therapy, a promising treatment option for GBM patients, is urgently needed.

Methods

We comprehensively evaluated lncRNA m6A modification patterns in m6A-sequencing (m6A-seq) data for GBM tissues and systematically investigated the immune and stromal regulators of these m6A-regulated lncRNAs. We used the single-sample gene-set enrichment analysis (ssGSEA) algorithm to investigate the difference in enriched tumor microenvironment (TME) infiltrating cells and the functional annotation of HSPA7 in individual GBM samples. Further, we validated that HSPA7 promoted the recruitment of macrophages into GBM TME in vitro, as well as in our GBM tissue section. We also explored its impact on the efficacy of ICB therapy using the patient-derived glioblastoma organoid (GBO) model.

Results

Here, we depicted the first transcriptome-wide m6A methylation profile of lncRNAs in GBM, revealing highly distinct lncRNA m6A modification patterns compared to those in normal brain tissues. We identified the m6A-modified pseudogene HSPA7 as a novel prognostic risk factor in GBM patients, with crucial roles in immunophenotype determination, stromal activation, and carcinogenic pathway activation. We confirmed that HSPA7 promoted macrophage infiltration and SPP1 expression via upregulating the YAP1 and LOX expression of glioblastoma stem cells (GSCs) in vitro and in our clinical GBM tumor samples. We also confirmed that knockdown of HSPA7 might increase the efficiency of anti-PD1 therapy utilizing the GBO model, highlighting its potential as a novel target for immunotherapy.

Conclusions

Our results indicated that HSPA7 could be a novel immunotherapy target for GBM patients.
Dispersal Limitation Expands the Diversity of Coral Microbiome Metacommunity in the South China Sea
Authors: Zhang Jiandong , Hu Anyi , Sun Yingting , Yang Qingsong , Dong Junde , Long Lijuan , Huang Sijun
Published: July 2021

The coral microbiome is one of the most complex microbial biospheres. However, the ecological processes shaping coral microbiome community assembly are not well understood. Here, we investigated the abundance, diversity, and community assembly mechanisms of coral-associated microbes from a highly diverse coral metacommunity in the South China Sea. Compared to seawater, the coral microbial metacommunity were defined by highly variable bacterial abundances among individual coral samples, high species evenness but not high species richness, high β-diversity, and a small core microbiome. We used variation partitioning analysis, neutral community model, and null model to disentangle the influences of different ecological processes in coral microbiome assembly. Measured physico-chemical parameters of the surrounding seawater and the spatial factor together explained very little of the variation in coral microbiome composition. Neutral processes only explained a minor component of the variation of coral microbial communities, suggesting a non-stochastic community assembly. Homogeneous and heterogeneous selection, but not dispersal, contributed greatly to the assembly of the coral microbiome. Such selection could be attributed to the within-host environments rather than the local environments. Our results demonstrated that dispersal limitation and host filtering contribute significantly to the assembly of discrete coral microbial regimes and expand the metacommunity diversity.
Spatial Autocorrelation Analysis Using MIG-seq Data Indirectly Estimated the Gamete and Larval Dispersal Range of the Blue Coral, Heliopora coerulea, Within Reefs
Authors: Mokodongan Daniel Frikli , Taninaka Hiroki , Sara La , Kikuchi Taisei , Yuasa Hideaki , Suyama Yoshihisa , Yasuda Nina
Published: July 2021

Spatial autocorrelation analysis is a well-established technique for detecting spatial structures and patterns in ecology. However, compared to inter-population genetic structure, much less studies examined spatial genetic structure (SGS) within a population by means of spatial autocorrelation analysis. More SGS analysis that compares the robustness of genome-wide single nucleotide polymorphisms (SNPs) and traditional population genetic markers in detecting SGS, and direct comparison between the estimated dispersal range based on SGS and the larval dispersal range of corals directly surveyed in the field would be important. In this study, we examined the SGS of a reef-building coral species, Heliopora coerulea, in two different reefs (Shiraho and Akaishi) using genome-wide SNPs derived from Multiplexed inter-simple sequence repeat (ISSR) genotyping by sequencing (MIG-seq) analysis and nine microsatellite loci for comparison. Microsatellite data failed to reveal significant spatial patterns when using the same number of samples as MIG-seq, whereas MIG-seq analysis revealed significant spatial autocorrelation patterns up to 750 m in both Shiraho and Akaishi reefs based on the maximum significant distance method. However, detailed spatial genetic analysis using fine-scale distance classes (25–200 m) found an x-intercept of 255–392 m in Shiraho and that of 258–330 m in Akaishi reef. The latter results agreed well with a previously reported direct field observation of larval dispersal, indicating that the larvae of H. coerulea settled within a 350 m range in Shiraho reef within one generation. Overall, our results empirically demonstrate that the x-intercept of the spatial correlogram agrees well with the larval dispersal distance that is most frequently found in field observations, and they would be useful for deciding effective conservation management units for maintenance and/or recovery within an ecological time scale.
Development of a High-Efficiency Immunomagnetic Enrichment Method for Detection of Human Norovirus via PAMAM Dendrimer/SA-Biotin Mediated Cascade-Amplification
Authors: Gao Junshan , Zhang Le , Xue Liang , Cai Weicheng , Qin Zhiwei , Yang Jiale , Liang Yanhui , Wang Linping , Chen Moutong , Ye Qinghua , Li Ying , Wang Juan , Wu Shi , Wu Qingping , Zhang Jumei
Published: July 2021

Human norovirus is a common cause of acute gastroenteritis worldwide, and oysters have been found to be the main carriers for its spread. The lack of efficient pre-treatment methods has been a major bottleneck limiting the detection of viruses in oysters. In this study, we established a novel immunomagnetic enrichment method using polyamidoamine (PAMAM) dendrimer/SA-biotin-mediated cascade amplification for reverse transcriptase quantitative real-time polymerase chain reaction (RT-qPCR) detection. We compared the capture efficiency of traditional immunomagnetic enrichment, biotin-amplified immunomagnetic enrichment, and PAMAM dendrimer/SA-biotin-mediated cascade-amplification immunomagnetic enrichment. The optimal capture efficiency of the novel method was 44.26 ± 1.45%, which increased by 183.17% (P < 0.01) and 18.09% (P < 0.05) compared with the first two methods, respectively. Three methods were all applied in detecting norovirus in 44 retail oysters, the detection rate of the PAMAM dendrimer/SA-biotin-mediated method was 25.0%, which was higher than those of traditional IME (15.90%) and SA-biotin-amplified IME (18.80%) by 9.1 and 6.2%, respectively. In conclusion, the novel method can be applied for the rapid detection of norovirus in oysters, which can help reduce the cost and time of detection and improve detection rates.
Comparative Transcriptome and Endophytic Bacterial Community Analysis of Morchella conica SH
Authors: Lü Bei B. , Wu Guo G. , Sun Yu , Zhang Liang S. , Wu Xiao , Jiang Wei , Li Peng , Huang Yan N. , Wang Jin B. , Zhao Yong C. , Liu Hua , Song Li L. , Mo Qin , Pan Ai H. , Yang Yan , Long Xuan Q. , Cui Wei D. , Zhang Chao , Wang Xu , Tang Xue M.
Published: July 2021

The precious rare edible fungus Morchella conica is popular worldwide for its rich nutrition, savory flavor, and varieties of bioactive components. Due to its high commercial, nutritional, and medicinal value, it has always been a hot spot. However, the molecular mechanism and endophytic bacterial communities in M. conica were poorly understood. In this study, we sequenced, assembled, and analyzed the genome of M. conica SH. Transcriptome analysis reveals significant differences between the mycelia and fruiting body. As shown in this study, 1,329 and 2,796 genes were specifically expressed in the mycelia and fruiting body, respectively. The Gene Ontology (GO) enrichment showed that RNA polymerase II transcription activity-related genes were enriched in the mycelium-specific gene cluster, and nucleotide binding-related genes were enriched in the fruiting body-specific gene cluster. Further analysis of differentially expressed genes in different development stages resulted in finding two groups with distinct expression patterns. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment displays that glycan degradation and ABC transporters were enriched in the group 1 with low expressed level in the mycelia, while taurine and hypotaurine metabolismand tyrosine metabolism-related genes were significantly enriched in the group 2 with high expressed level in mycelia. Moreover, a dynamic shift of bacterial communities in the developing fruiting body was detected by 16S rRNA sequencing, and co-expression analysis suggested that bacterial communities might play an important role in regulating gene expression. Taken together, our study provided a better understanding of the molecular biology of M. conica SH and direction for future research on artificial cultivation.
Vertical Stratification of Dissolved Organic Matter Linked to Distinct Microbial Communities in Subtropic Estuarine Sediments
Authors: Wang Wenxiu , Tao Jianchang , Yu Ke , He Chen , Wang Jianjun , Li Penghui , Chen Hongmei , Xu Bu , Shi Quan , Zhang Chuanlun
Published: July 2021

Dissolved organic matter (DOM) provides carbon substrates and energy sources for sediment microbes driving benthic biogeochemical processes. The interactions between microbes and DOM are dynamic and complex and require the understanding based on fine-scale microbial community and physicochemical profiling. In this study, we characterized the porewater DOM composition in a 300-cm sediment core from the Pearl River estuary, China, and examined the interactions between DOM and archaeal and bacterial communities. DOM composition were highly stratified and associated with changing microbial communities. Compared to bacteria, the amplicon sequence variants of archaea showed significant Pearson correlations (r≥ 0.65,P< 0.01) with DOM molecules of low H/C ratios, high C number and double bond equivalents, indicating that the distribution of archaea was closely correlated to recalcitrant DOM while bacteria were associated with relatively labile compounds. This was supported by the presence of auxiliary enzyme families essential for lignin degradation andbcrABCD, UbiXgenes for anaerobic aromatic reduction in metagenome-assembled genomes of Bathyarchaeia. Our study demonstrates that niche differentiation between benthic bacteria and archaea may have important consequences in carbon metabolism, particularly for the transformation of recalcitrant organic carbon that may be predominant in aged marine sediments.
A Validated Mathematical Model of the Cytokine Release Syndrome in Severe COVID-19
Authors: Reis Ruy Freitas , Pigozzo Alexandre Bittencourt , Bonin Carla Rezende Barbosa , Quintela Barbara de Melo , Pompei Lara Turetta , Vieira Ana Carolina , Silva Larissa de Lima e , Xavier Maicom Peters , Weber dos Santos Rodrigo , Lobosco Marcelo
Published: July 2021

By June 2021, a new contagious disease, the Coronavirus disease 2019 (COVID-19), has infected more than 172 million people worldwide, causing more than 3.7 million deaths. Many aspects related to the interactions of the disease’s causative agent, SAR2-CoV-2, and the immune response are not well understood: the multiscale interactions among the various components of the human immune system and the pathogen are very complex. Mathematical and computational tools can help researchers to answer these open questions about the disease. In this work, we present a system of fifteen ordinary differential equations that models the immune response to SARS-CoV-2. The model is used to investigate the hypothesis that the SARS-CoV-2 infects immune cells and, for this reason, induces high-level productions of inflammatory cytokines. Simulation results support this hypothesis and further explain why survivors have lower levels of cytokines levels than non-survivors.
Remote Homology Detection Identifies a Eukaryotic RPA DBD-C-like DNA Binding Domain as a Conserved Feature of Archaeal Rpa1-Like Proteins
Authors: MacNeill Stuart A.
Published: July 2021

The eukaryotic single-stranded DNA binding factor replication protein A (RPA) is essential for DNA replication, repair and recombination. RPA is a heterotrimer containing six related OB folds and a winged helix-turn-helix (wH) domain. The OB folds are designated DBD-A through DBD-F, with DBD-A through DBD-D being directly involved in ssDNA binding. DBD-C is located at the C-terminus of the RPA1 protein and has a distinctive structure that includes an integral C4 zinc finger, while the wH domain is found at the C-terminus of the RPA2 protein. Previously characterised archaeal RPA proteins fall into a number of classes with varying numbers of OB folds, but one widespread class includes proteins that contain a C4 or C3H zinc finger followed by a 100–120 amino acid C-terminal region reported to lack detectable sequence or structural similarity. Here, the sequences spanning this zinc finger and including the C-terminal region are shown to comprise a previously unrecognised DBD-C-like OB fold, confirming the evolutionary relatedness of this group of archaeal RPA proteins to eukaryotic RPA1. The evolutionary relationship between eukaryotic and archaeal RPA is further underscored by the presence of RPA2-like proteins comprising an OB fold and C-terminal winged helix (wH) domain in multiple species and crucially, suggests that several biochemically characterised archaeal RPA proteins previously thought to exist as monomers are likely to be RPA1-RPA2 heterodimers.
Pancreas-Brain Crosstalk
Authors: Lkhagvasuren Battuvshin , Mee-inta Onanong , Zhao Zi-Wei , Hiramoto Tetsuya , Boldbaatar Damdindorj , Kuo Yu-Min
Published: July 2021

The neural regulation of glucose homeostasis in normal and challenged conditions involves the modulation of pancreatic islet-cell function. Compromising the pancreas innervation causes islet autoimmunity in type 1 diabetes and islet cell dysfunction in type 2 diabetes. However, despite the richly innervated nature of the pancreas, islet innervation remains ill-defined. Here, we review the neuroanatomical and humoral basis of the cross-talk between the endocrine pancreas and autonomic and sensory neurons. Identifying the neurocircuitry and neurochemistry of the neuro-insular network would provide clues to neuromodulation-based approaches for the prevention and treatment of diabetes and obesity.
SyNC, a Computationally Extensive and Realistic Neural Net to Identify Relative Impacts of Synaptopathy Mechanisms on Glutamatergic Neurons and Their Networks in Autism and Complex Neurological Disorders
Authors: Chatterjee Rounak , Paluh Janet L. , Chowdhury Souradeep , Mondal Soham , Raha Arnab , Mukherjee Amitava
Published: July 2021

Synaptic function and experience-dependent plasticity across multiple synapses are dependent on the types of neurons interacting as well as the intricate mechanisms that operate at the molecular level of the synapse. To understand the complexity of information processing at synaptic networks will rely in part on effective computational models. Such models should also evaluate disruptions to synaptic function by multiple mechanisms. By co-development of algorithms alongside hardware, real time analysis metrics can be co-prioritized along with biological complexity. The hippocampus is implicated in autism spectrum disorders (ASD) and within this region glutamatergic neurons constitute 90% of the neurons integral to the functioning of neuronal networks. Here we generate a computational model referred to as ASD interrogator (ASDint) and corresponding hardware to enable in silicon analysis of multiple ASD mechanisms affecting glutamatergic neuron synapses. The hardware architecture Synaptic Neuronal Circuit, SyNC, is a novel GPU accelerator or neural net, that extends discovery by acting as a biologically relevant realistic neuron synapse in real time. Co-developed ASDint and SyNC expand spiking neural network models of plasticity to comparative analysis of retrograde messengers. The SyNC model is realized in an ASIC architecture, which enables the ability to compute increasingly complex scenarios without sacrificing area efficiency of the model. Here we apply the ASDint model to analyse neuronal circuitry dysfunctions associated with autism spectral disorder (ASD) synaptopathies and their effects on the synaptic learning parameter and demonstrate SyNC on an ideal ASDint scenario. Our work highlights the value of secondary pathways in regard to evaluating complex ASD synaptopathy mechanisms. By comparing the degree of variation in the synaptic learning parameter to the response obtained from simulations of the ideal scenario we determine the potency and time of the effect of a particular evaluated mechanism. Hence simulations of such scenarios in even a small neuronal network now allows us to identify relative impacts of changed parameters and their effect on synaptic function. Based on this, we can estimate the minimum fraction of a neuron exhibiting a particular dysfunction scenario required to lead to complete failure of a neural network to coordinate pre-synaptic and post-synaptic outputs.
Children With Dyscalculia Show Hippocampal Hyperactivity During Symbolic Number Perception
Authors: Üstün Sertaç , Ayyıldız Nazife , Kale Emre H. , Mançe Çalışır Öykü , Uran Pınar , Öner Özgür , Olkun Sinan , Çiçek Metehan
Published: July 2021

Dyscalculia is a learning disability affecting the acquisition of arithmetical skills in children with normal intelligence and age-appropriate education. Two hypotheses attempt to explain the main cause of dyscalculia. The first hypothesis suggests that a problem with the core mechanisms of perceiving (non-symbolic) quantities is the cause of dyscalculia (core deficit hypothesis), while the alternative hypothesis suggests that dyscalculics have problems only with the processing of numerical symbols (access deficit hypothesis). In the present study, the symbolic and non-symbolic numerosity processing of typically developing children and children with dyscalculia were examined with functional magnetic resonance imaging (fMRI). Control (n = 15, mean age: 11.26) and dyscalculia (n = 12, mean age: 11.25) groups were determined using a wide-scale screening process. Participants performed a quantity comparison paradigm in the fMRI with two number conditions (dot and symbol comparison) and two difficulty levels (0.5 and 0.7 ratio). The results showed that the bilateral intraparietal sulcus (IPS), left dorsolateral prefrontal cortex (DLPFC) and left fusiform gyrus (so-called “number form area”) were activated for number perception as well as bilateral occipital and supplementary motor areas. The task difficulty engaged bilateral insular cortex, anterior cingulate cortex, IPS, and DLPFC activation. The dyscalculia group showed more activation in the left orbitofrontal cortex, left medial prefrontal cortex, and right anterior cingulate cortex than the control group. The dyscalculia group showed left hippocampus activation specifically for the symbolic condition. Increased left hippocampal and left-lateralized frontal network activation suggest increased executive and memory-based compensation mechanisms during symbolic processing for dyscalculics. Overall, our findings support the access deficit hypothesis as a neural basis for dyscalculia.
Striatal Control of Movement: A Role for New Neuronal (Sub-) Populations?
Authors: Fieblinger Tim
Published: July 2021

The striatum is a very heterogenous brain area, composed of different domains and compartments, albeit lacking visible anatomical demarcations. Two populations of striatal spiny projection neurons (SPNs) build the so-called direct and indirect pathway of the basal ganglia, whose coordinated activity is essential to control locomotion. Dysfunction of striatal SPNs is part of many movement disorders, such as Parkinson’s disease (PD) and L-DOPA-induced dyskinesia. In this mini review article, I will highlight recent studies utilizing single-cell RNA sequencing to investigate the transcriptional profiles of striatal neurons. These studies discover that SPNs carry a transcriptional signature, indicating both their anatomical location and compartmental identity. Furthermore, the transcriptional profiles reveal the existence of additional distinct neuronal populations and previously unknown SPN sub-populations. In a parallel development, studies in rodent models of PD and L-DOPA-induced dyskinesia (LID) report that direct pathway SPNs do not react uniformly to L-DOPA therapy, and that only a subset of these neurons is underlying the development of abnormal movements. Together, these studies demonstrate a new level of cellular complexity for striatal (dys-) function and locomotor control.
Injection of Anti-proBDNF Attenuates Hippocampal-Dependent Learning and Memory Dysfunction in Mice With Sepsis-Associated Encephalopathy
Authors: Cui Yan-Hui , Zhou Shi-Fen , Liu Yu , Wang Shuang , Li Fang , Dai Ru-Ping , Hu Zhao-Lan , Li Chang-Qi
Published: July 2021

Sepsis-associated encephalopathy (SAE) is a risk factor for cognitive and memory dysfunction; however, the mechanism remains unclear. Brain-derived neurotrophic factor (BDNF) was reported to have a positive effect on cognition and emotion regulation, but the study of its precursor, proBDNF, has been limited. This study aimed to elucidate the effects and associated mechanisms of hippocampal proBDNF in a lipopolysaccharide (LPS)-induced SAE mouse model. In this study, we found that the mice exhibited cognitive dysfunction on day 7 after LPS injection. The expression of proBDNF and its receptor, p75NTR, was also increased in the hippocampus, while the levels of BDNF and its receptor, TrkB, were decreased. A co-localization study showed that proBDNF and p75NTR were mainly co-localized with neurons. Furthermore, LPS treatment reduced the expression of NeuN, Nissl bodies, GluR4, NR1, NR2A, and NR2B in the hippocampus of SAE mice. Furthermore, an intrahippocampal or intraperitoneal injection of anti-proBDNF antibody was able to ameliorate LPS-induced cognitive dysfunction and restore the expression of NeuN, Nissl bodies, GluR4, NR1, NR2A, NR2B, and PSD95. These results indicated that treatment with brain delivery by an intrahippocampal and systemic injection of mAb-proBDNF may represent a potential therapeutic strategy for treating patients with SAE.
Squamous and Respiratory Metaplasia After Olfactory Mucosal Resection
Authors: Mori Eri , Ueha Rumi , Kondo Kenji , Funada Shotaro , Shimmura Hajime , Kanemoto Kai , Tanaka Hirotaka , Nishijima Hironobu , Otori Nobuyoshi , Yamasoba Tatsuya , Kojima Hiromi
Published: July 2021

Resection of the olfactory mucosa (OM) is sometimes unavoidable during surgery; however, it is not known whether the OM can completely recover thereafter. The aim of this study was to uncover whether the OM fully recovers after mucosal resection and describe the process of OM regeneration. 8-week-old male Sprague–Dawley rats (n = 18) were subjected to OM resection at the nasal septum; six rats were euthanized for histological examination 0, 30, and 90 days after surgery. Immunohistochemistry was performed to identify olfactory receptor neuron (ORN) lineage cells [mature and immature ORNs and ORN progenitors, and olfactory ensheathing cells (OECs)], as well as dividing and apoptotic cells. Squamous and respiratory metaplasia and inflammatory cell infiltration were also assessed. On day 30 after resection, the mucosa had regenerated, and mainly contained thin nerve bundles, basal cells, and immature ORNs, with a few mature ORNs and OECs. On day 90, the repaired nasal mucosa had degenerated into stratified squamous or ciliated pseudostratified columnar epithelia, with reducing ORNs. The lamina propria contained numerous macrophages. Partial regeneration was observed within 1 month after OM resection, whereas subsequent degeneration into squamous and respiratory epithelia occurred within 3 months. Given the poor persistence of ORNs and OECs, OM resection is likely to result in olfactory impairment. Overall, surgeons should be cautious not to injure the OM during surgery.
Dysfunctional Brain Dynamics of Parkinson's Disease and the Effect of Acute Deep Brain Stimulation
Authors: Li Zhibao , Ren Guoping , Liu Chong , Wang Qiao , Liang Kun , Han Chunlei , Qiao Hui , Zhang Jianguo , Wang Qun , Meng Fangang
Published: July 2021

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, and deep brain stimulation (DBS) can effectively alleviate PD symptoms. Although previous studies have detected network features of PD and DBS, few studies have considered their dynamic characteristics.

Objective: We tested two hypotheses. (1) Reduced brain dynamics, as evidenced by slowed microstate dynamic change, is a characteristic of PD and is related to the movement disorders of patients with PD. (2) Therapeutic acute DBS can partially reverse slow brain dynamics in PD to healthy levels.

Methods: We used electroencephalography (EEG) microstate analysis based on high density (256-channel) EEG to detect the effects of PD and DBS on brain dynamic changes on a sub-second timescale. We compared 21 healthy controls (HCs) with 20 patients with PD who were in either DBS-OFF or DBS-ON states. Assessment of movement disorder using the Unified Parkinson's Disease Rating Scale III was correlated with microstate parameters.

Results: Compared with HCs, patients with PD displayed a longer mean microstate duration with reduced occurrence per second, which were significantly associated with movement disorders. In patients with PD, some parameters of microstate analysis were restored toward healthy levels after DBS.

Conclusions: Resting-state EEG microstate analysis is an important tool for investigating brain dynamic changes in PD and DBS. PD can slow down brain dynamic change, and therapeutic acute DBS can partially reverse this change toward a healthy level.
Long Non-coding RNA T-uc.189 Modulates Neural Progenitor Cell Fate by Regulating Srsf3 During Mouse Cerebral Cortex Development
Authors: Zhang Meng , Zhou Junjie , Jiao Li , Xu Longjiang , Hou Lin , Yin Bin , Qiang Boqin , Lu Shuaiyao , Shu Pengcheng , Peng Xiaozhong
Published: July 2021

Neurogenesis is a complex process that depends on the delicate regulation of spatial and temporal gene expression. In our previous study, we found that transcribed ultra-conserved regions (T-UCRs), a class of long non-coding RNAs that contain UCRs, are expressed in the developing nervous systems of mice, rhesus monkeys, and humans. In this study, we first detected the full-length sequence of T-uc.189, revealing that it was mainly concentrated in the ventricular zone (VZ) and that its expression decreased as the brain matured. Moreover, we demonstrated that knockdown of T-uc.189 inhibited neurogenesis. In addition, we found that T-uc.189 positively regulated the expression of serine-arginine-rich splicing factor 3 (Srsf3). Taken together, our results are the first to demonstrate that T-uc.189 regulates the expression of Srsf3 to maintain normal neurogenesis during cortical development.
A Brief Journey into the History of and Future Sources and Uses of Fatty Acids
Authors: Cerone Michela , Smith Terry K.
Published: July 2021

Fats and lipids have always had a primary role in the history of humankind, from ancient civilisations to the modern and contemporary time, going from domestic and cosmetic uses, to the first medical applications and later to the large-scale industrial uses for food, pharmaceutical, cosmetics, and biofuel production. Sources and uses of those have changed during time following the development of chemical sciences and industrial technological advances. Plants, fish, and animal fats have represented the primary source of lipids and fats for century. Nowadays, the use of fatty acid sources has taken a turn: industries are mainly interested in polyunsaturated fatty acids (PUFAs), which have beneficial properties in human health; and also, for high-value fatty acids product for innovative and green production of biofuel and feedstocks. Thus, the constant increase in demand of fatty acids, the fact that marine and vegetable sources are not adequate to meet the high level of fatty acids required worldwide and climate change, have determined the necessity of the search for renewable and sustainable sources for fatty acids. Biotechnological advances and bioengineering have started looking at the genetic modification of algae, bacteria, yeasts, seeds, and plants to develop cell factory able to produce high value fatty acid products in a renewable and sustainable manner. This innovative approach applied to FA industry is a peculiar example of how biotechnology can serve as a powerful mean to drive the production of high value fatty acid derivatives on the concept of circular bioeconomy, based on the reutilisation of organic resources for alternative and sustainable productive patterns that are environmentally friendly.
Shelf-Life Extension of Large Yellow Croaker (Larimichthys crocea) Using Active Coatings Containing Lemon Verbena (Lippa citriodora Kunth.) Essential Oil
Authors: Li Bo , Wang Xuesong , Gao Xin , Ma Xuan , Zhang Leilei , Mei Jun , Xie Jing
Published: July 2021

Active coating could improve the fish quality and extend the shelf life. This study investigates the effect of locust bean gum (LBG) and sodium alginate (SA) active coatings containing lemon verbena (Lippa citriodora Kunth.) essential oil (LVEO) emulsions on microbiological, physicochemical and organoleptic evaluation of large yellow croaker (Larimichthys crocea) samples during refrigerated storage at 4°C. Results showed that LBG-SA coatings incorporated with 0.30 or 0.60% LVEO emulsions significantly inhibited the growth of mesophile bacteria, Pseudomonas spp., H2S-producing bacteria, lactic acid bacteria (LAB) and psychrophilic bacteria, and reduce the productions of trimethylamine (TMA), total volatile basic nitrogen (TVB-N) and ATP-related compounds. Further, the LVEO treatments also retarded the water migration and maintained the organoleptic evaluation results of large yellow croaker during storage at 4°C. In conclusion, the LBG-SA active coatings incorporated with LVEO emulsions maintained the quality and extended the shelf life of large yellow croaker during refrigerated storage.
Dual Inhibition of PARP and the Intra-S/G2 Cell Cycle Checkpoints Results in Highly Effective Radiosensitization of HPV-Positive HNSCC Cells
Authors: Hintelmann Katharina , Berenz Thomas , Kriegs Malte , Christiansen Sabrina , Gatzemeier Fruzsina , Struve Nina , Petersen Cordula , Betz Christian , Rothkamm Kai , Oetting Agnes , Rieckmann Thorsten
Published: July 2021

In head and neck squamous cell carcinoma (HNSCC), tumors positive for human papillomavirus (HPV) represent a distinct biological entity with favorable prognosis. An enhanced radiation sensitivity of these tumors is evident in the clinic and on the cellular level when comparing HPV-positive and HPV-negative HNSCC cell lines. We could show that the underlying mechanism is a defect in DNA double-strand break repair associated with a profound and sustained G2 arrest. This defect can be exploited by molecular targeting approaches additionally compromising the DNA damage response to further enhance their radiation sensitivity, which may offer new opportunities in the setting of future de-intensified regimes. Against this background, we tested combined targeting of PARP and the DNA damage-induced intra-S/G2 cell cycle checkpoints to achieve effective radiosensitization. Enhancing CDK1/2 activity through the Wee1 inhibitor adavosertib or a combination of Wee1 and Chk1 inhibition resulted in an abrogation of the radiation-induced G2 cell cycle arrest and induction of replication stress as assessed by γH2AX and chromatin-bound RPA levels in S phase cells. Addition of the PARP inhibitor olaparib had little influence on these endpoints, irrespective of checkpoint inhibition. Combined PARP/Wee1 targeting did not result in an enhancement in the absolute number of residual, radiation induced 53BP1 foci as markers of DNA double-strand breaks but it induced a shift in foci numbers from S/G2 to G1 phase cells. Most importantly, while sole checkpoint or PARP inhibition induced moderate radiosensitization, their combination was clearly more effective, while exerting little effect in p53/G1 arrest proficient normal human fibroblasts, thus indicating tumor specificity. We conclude that the combined inhibition of PARP and the intra-S/G2 checkpoint is a highly effective approach for the radiosensitization of HPV-positive HNSCC cells and may represent a viable alternative for the current standard of concomitant cisplatin-based chemotherapy. In vivo studies to further evaluate the translational potential are highly warranted.
Case Report: Discovery a Novel SARS-CoV-2 Variant in a Six-Months Long-Term Swab Positive Female Suffering From Non-Hodgkin Lymphoma
Authors: Capoluongo Ettore , Nardelli Carmela , Esposito Maria Valeria , Buonomo Antonio Riccardo , Gelzo Monica , Pinchera Biagio , Zappulo Emanuela , Viceconte Giulio , Portella Giuseppe , Setaro Mario , Gentile Ivan , Castaldo Giuseppe
Published: July 2021

Background

We report the case of a woman with non-Hodgkin lymphoma who remained positive on the molecular assay for SARS-CoV-2 for six months: she has never experienced a severe form of COVID-19 although in absence of seroconversion.

Methods

The whole SARS-CoV-2 genome analysis was performed by the CleanPlex SARS-CoV-2 Research and Surveillance NGS Panel (PARAGON GENOMICS, Hayward, USA).

Results

We found twenty-two mutations in SARS-CoV-2 genome and a novel deleterious ORF3a frameshift c.766_769del corresponding to a unique and novel lineage. The region affected by this frameshift variant is reported as being important in determining SARS-CoV-2 immunogenicity. Patient’s immunophenotype showed the absence of B lymphocytes and significantly reduced T-cell count. Only after the treatment with hyperimmune plasma she finally became negative on the swab.

Conclusions

Our findings could be helpful in the management of patients with immunodeficiency, particularly when novel variants, potentially altering the virus immune response, are present.
DNA Polymerase Iota Promotes Esophageal Squamous Cell Carcinoma Proliferation Through Erk-OGT-Induced G6PD Overactivation
Authors: Su Zhenzi , Gao Aidi , Li Xiaoqing , Zou Shitao , He Chao , Wu Jinchang , Ding Wei-Qun , Zhou Jundong
Published: July 2021

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers with rapid progression and a high mortality rate. Our previous study demonstrated that DNA polymerase iota (Pol ι) is overexpressed in ESCC tumors and correlates with poor prognosis. However, its role in ESCC proliferation remains obscure. We report here that Pol ι promotes ESCC proliferation and progression through Erk- O-GlcNAc transferase (OGT) regulated Glucose-6-phosphate dehydrogenase (G6PD) overactivation. Cell clonogenic ability was assessed by colony formation assay. Cell proliferation was assessed by EdU incorporation assay. Our transcriptome data was reanalyzed by GSEA and validated by analysis of cellular metabolism, G6PD activity, and cellular NADPH concentration. The level of Pol ι, OGT, G6PD and O-GlcNAcylation in ESCC cells and patient samples were analyzed. The MEK inhibitor PD98059 was applied to confirm OGT expression regulation by the Erk signaling. The G6PD inhibitor polydatin was used to examine the role of G6PD activation in Pol ι promoted proliferation. We found that Pol ι promotes ESCC proliferation. It shunted the glucose flux towards the pentose phosphate pathway (PPP) by activating G6PD through OGT-promoted O-GlcNAcylation. The expression of OGT was positively correlated with Pol ι expression and O-GlcNAcylation. Notably, elevated O-GlcNAcylation was correlated with poor prognosis in ESCC patients. Pol ι was shown to stimulate Erk signaling to enhance OGT expression, and the G6PD inhibitor polydatin attenuated Pol ι induced tumor growth in vitro and in vivo. In conclusion, Pol ι activates G6PD through Erk-OGT-induced O-GlcNAcylation to promote the proliferation and progression of ESCC, supporting the notion that Pol ι is a potential biomarker and therapeutic target of ESCC.