bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparative Characterization and Expression Profiling Analysis of Fructokinase and Fructokinase-like Genes: Exploring Their Roles in Cucumber Development and Chlorophyll Biosynthesis
Authors: Fan Lianxue , Zhang Wenshuo , Xu Zhuo , Li Shengnan , Liu Dong , Wang Lili , Zhou Xiuyan
Published: November 2022

Fructokinase (FRK) and fructokinase-like (FLN), belonging to the phosphofructokinase B type subfamily, share substantial sequence similarity, and are crucial in various plant physiological processes. However, there is limited information regarding what functionally differentiates plant FRKs from FLNs. Here, a total of three CsFRKs and two CsFLNs were identified from the cucumber genome. Their significant difference lay in the structure of their G/AXGD motif, which existed as GAGD in CsFRKs, but as G/ASGD in CsFLNs. Comparative phylogenetic analysis classified CsFRKs and CsFLNs into five sub-branches consistent with their quite different exon/intron organizations. Both transcriptome data and RT-qPCR analyses revealed that CsFRK3 was the most active gene, with the highest expression in the majority of tissues tested. Moreover, the expression levels of two putative plastidic genes, CsFRK1 and CsFLN2, were significantly positively associated with chlorophyll accumulation in the chlorophyll-reduced cucumber mutant. Briefly, both CsFRK and CsFLN genes were involved in the development of sink tissues, especially CsFRK3. CsFRK1 and CsFLN2 were recognized as candidates in the chlorophyll biosynthesis pathway of cucumber. These results would greatly assist in further investigation on functional characterization of FRKs and FLNs, especially in the development and chlorophyll biosynthesis of cucumber.
Identification and Expression Analysis of the NPF Genes in Cotton
Authors: Dong Qiang , Wang Guoxin , Iqbal Asif , Muhammad Noor , Wang Xiangru , Gui Huiping , Zhang Hengheng , Kayoumu Mirezhatijiang , Li Xiaotong , Zhang Xiling , Song Meizhen
Published: November 2022

The NPF (NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER FAMILY) transports various substrates, including nitrogen (N), which is essential for plant growth and development. Although many NPF homologs have been identified in various plants, limited studies on these proteins have been reported in cotton. This study identified 75, 71, and 150 NPF genes in Gossypium arboreum, G. raimondii, and G. hirsutum, respectively, via genome-wide analyses. The phylogenetic tree indicated that cotton NPF genes are subdivided into eight subgroups, closely clustered with Arabidopsis orthologues. The chromosomal location, gene structure, motif compositions, and cis-elements have been displayed. Moreover, the collinearity analysis showed that whole-genome duplication event has played an important role in the expansion and diversification of the NPF gene family in cotton. According to the transcriptome and qRT-PCR analyses, several GhNPFs were induced by the nitrogen deficiency treatment. Additional functional experiments revealed that virus-induced silencing (VIGS) of the GhNPF6.14 gene affects the growth and N absorption and accumulation in cotton. Thus, this study lays the foundation for further functional characterization of NPF genes in cotton.
Transforming Growth Factorβ1 Overexpression Is Associated with Insulin Resistance and Rapidly Progressive Kidney Fibrosis under Diabetic Conditions
Authors: D’Alessandro Valeria Fridman , Takeshita Atsuro , Yasuma Taro , Toda Masaaki , D’Alessandro-Gabazza Corina N. , Okano Yuko , Tharavecharak Suphachai , Inoue Chisa , Nishihama Kota , Fujimoto Hajime , Kobayashi Tetsu , Yano Yutaka , Gabazza Esteban C.
Published: November 2022

Diabetes mellitus is a global health problem. Diabetic nephropathy is a common complication of diabetes mellitus and the leading cause of end-stage renal disease. The clinical course, response to therapy, and prognosis of nephropathy are worse in diabetic than in non-diabetic patients. The role of transforming growth factorβ1 in kidney fibrosis is undebatable. This study assessed whether the overexpression of transforming growth factorβ1 is associated with insulin resistance and the rapid progression of transforming growth factorβ1-mediated nephropathy under diabetic conditions. Diabetes mellitus was induced with streptozotocin in wild-type mice and transgenic mice with the kidney-specific overexpression of human transforming growth factorβ1. Mice treated with saline were the controls. Glucose tolerance and kidney fibrosis were evaluated. The blood glucose levels, the values of the homeostasis model assessment for insulin resistance, and the area of kidney fibrosis were significantly increased, and the renal function was significantly impaired in the diabetic transforming growth factorβ1 transgenic mice compared to the non-diabetic transgenic mice, diabetic wild-type mice, and non-diabetic mice. Transforming growth factorβ1 impaired the regulatory effect of insulin on glucose in the hepatocyte and skeletal muscle cell lines. This study shows that transforming growth factorβ1 overexpression is associated with insulin resistance and rapidly progressive kidney fibrosis under diabetic conditions in mice.
NB-LRR Lineage-Specific Equipment Is Sorted Out by Sequence Pattern Adaptation and Domain Segment Shuffling
Authors: Andolfo Giuseppe , Di Donato Antimo , Ercolano Maria Raffaella
Published: November 2022

The nucleotide-binding and leucine-rich repeat (NB-LRR) genes, also known as resistance (R)-genes, play an important role in the activation of immune responses. In recent years, large-scale studies have been performed to highlight the diversification of plant NB-LRR repertories. It is well known that, to provide new functionalities, NB-LRR sequences are subject to duplication, domain fusions and acquisition and other kinds of mutations. Although some mechanisms that govern NB-LRR protein domain adaptations have been uncovered, to retrace the plant-lineage-specific evolution routes of R protein structure, a multi-genome comparative analysis was performed. This study allowed us to define groups of genes sharing homology relationships across different species. It is worth noting that the most populated groups contained well-characterized R proteins. The arsenal profile of such groups was investigated in five botanical families, including important crop species, to underline specific adaptation signatures. In addition, the dissection of 70 NB domains of well-characterized R-genes revealed the NB core motifs from which the three main R protein classes have been diversified. The structural remodeling of domain segments shaped the specific NB-LRR repertoires observed in each plant species. This analysis provided new evolutionary and functional insights on NB protein domain shuffling. Taken together, such findings improved our understanding of the molecular adaptive selection mechanisms occurring at plant R loci.
A Review on Stimuli-Actuated 3D Micro/Nanostructures for Tissue Engineering and the Potential of Laser-Direct Writing via Two-Photon Polymerization for Structure Fabrication
Authors: Calin Bogdan Stefanita , Paun Irina Alexandra
Published: November 2022

In this review, we present the most recent and relevant research that has been done regarding the fabrication of 3D micro/nanostructures for tissue engineering applications. First, we make an overview of 3D micro/nanostructures that act as backbone constructs where the seeded cells can attach, proliferate and differentiate towards the formation of new tissue. Then, we describe the fabrication of 3D micro/nanostructures that are able to control the cellular processes leading to faster tissue regeneration, by actuation using topographical, mechanical, chemical, electric or magnetic stimuli. An in-depth analysis of the actuation of the 3D micro/nanostructures using each of the above-mentioned stimuli for controlling the behavior of the seeded cells is provided. For each type of stimulus, a particular recent application is presented and discussed, such as controlling the cell proliferation and avoiding the formation of a necrotic core (topographic stimulation), controlling the cell adhesion (nanostructuring), supporting the cell differentiation via nuclei deformation (mechanical stimulation), improving the osteogenesis (chemical and magnetic stimulation), controlled drug-delivery systems (electric stimulation) and fastening tissue formation (magnetic stimulation). The existing techniques used for the fabrication of such stimuli-actuated 3D micro/nanostructures, are briefly summarized. Special attention is dedicated to structures’ fabrication using laser-assisted technologies. The performances of stimuli-actuated 3D micro/nanostructures fabricated by laser-direct writing via two-photon polymerization are particularly emphasized.
Bilirubin Prevents the TH+ Dopaminergic Neuron Loss in a Parkinson’s Disease Model by Acting on TNF-α
Authors: Jayanti Sri , Moretti Rita , Tiribelli Claudio , Gazzin Silvia
Published: November 2022

Parkinson’s disease (PD), the fastest-growing movement disorder, is still challenged by the unavailability of disease-modifying therapy. Mildly elevated levels of unconjugated bilirubin (UCB, PubChem CID 5280352) have been shown to be protective against several extra-CNS diseases, and the effect is attributed to its well-known anti-oxidant and anti-inflammatory capability. We explored the neuroprotective effect of low concentrations of UCB (from 0.5 to 4 µM) in our PD model based on organotypic brain cultures of substantia nigra (OBCs-SN) challenged with a low dose of rotenone (Rot). UCB at 0.5 and 1 µM fully protects against the loss of TH+ (dopaminergic) neurons (DOPAn). The alteration in oxidative stress is involved in TH+ positive neuron demise induced by Rot, but is not the key player in UCB-conferred protection. On the contrary, inflammation, specifically tumor necrosis factor alpha (TNF-α), was found to be the key to UCB protection against DOPAn sufferance. Further work will be needed to introduce the use of UCB into clinical settings, but determining that TNF-α plays a key role in PD may be crucial in designing therapeutic options.
Genome-Scale Identification, Classification, and Expression Profiling of MYB Transcription Factor Genes in Cinnamomum camphora
Authors: Luan Xiaoyue , Xu Wenlin , Zhang Jiaqi , Shen Tengfei , Chen Caihui , Xi Mengli , Zhong Yongda , Xu Meng
Published: November 2022

The camphor tree (Cinnamomum camphora (L.) Presl.) is the representative species of subtropical evergreen broadleaved forests in eastern Asia and an important raw material for essential oil production worldwide. Although MYBs have been comprehensively characterized and their functions have been partially resolved in many plants, it has not been explored in C. camphora. In this study, 121 CcMYBs were identified on 12 chromosomes in the whole genome of C. camphora and found that CcMYBs were mainly expanded by segmental duplication. They were divided into 28 subgroups based on phylogenetic analysis and gene structural characteristics. In the promoter regions, numerous cis-acting elements were related to biological processes. Analysis of RNA sequencing data from seven tissues showed that CcMYBs exhibited different expression profiles, suggesting that they have various roles in camphor tree development. In addition, combined with the correlation analysis of structural genes in the flavonoid synthesis pathway, we identified CcMYBs from three subgroups that might be related to the flavonoid biosynthesis pathway. This study systematically analyzed CcMYBs in C. camphora, which will set the stage for subsequent research on the functions of CcMYBs during their lifetime and provide valuable insights for the genetic improvement of camphor trees.
Identification of NRAS Diagnostic Biomarkers and Drug Targets for Endometrial Cancer—An Integrated in Silico Approach
Authors: Alessandro Larsen , Low Kat-Jun Eric , Abushelaibi Aisha , Lim Swee-Hua Erin , Cheng Wan-Hee , Chang Sook-keng , Lai Kok-Song , Sum Yap Wai , Maran Sathiya
Published: November 2022

The diagnosis of endometrial cancer involves sequential, invasive tests to assess the thickness of the endometrium by a transvaginal ultrasound scan. In 6–33% of cases, endometrial biopsy results in inadequate tissue for a conclusive pathological diagnosis and 6% of postmenopausal women with non-diagnostic specimens are later discovered to have severe endometrial lesions. Thus, identifying diagnostic biomarkers could offer a non-invasive diagnosis for community or home-based triage of symptomatic or asymptomatic women. Herein, this study identified high-risk pathogenic nsSNPs in the NRAS gene. The nsSNPs of NRAS were retrieved from the NCBI database. PROVEAN, SIFT, PolyPhen-2, SNPs&GO, PhD-SNP and PANTHER were used to predict the pathogenicity of the nsSNPs. Eleven nsSNPs were identified as “damaging”, and further stability analysis using I-Mutant 2.0 and MutPred 2 indicated eight nsSNPs to cause decreased stability (DDG scores < −0.5). Post-translational modification and protein–protein interactions (PPI) analysis showed putative phosphorylation sites. The PPI network indicated a GFR-MAPK signalling pathway with higher node degrees that were further evaluated for drug targets. The P34L, G12C and Y64D showed significantly lower binding affinity towards GTP than wild-type. Furthermore, the Kaplan–Meier bioinformatics analyses indicated that the NRAS gene deregulation affected the overall survival rate of patients with endometrial cancer, leading to prognostic significance. Findings from this could be considered novel diagnostic and therapeutic markers.
Hormone Regulation of CCCH Zinc Finger Proteins in Plants
Authors: Wang Qiao , Song Shangfa , Lu Xintong , Wang Yiqing , Chen Yan , Wu Xiuwen , Tan Li , Chai Guohua
Published: November 2022

CCCH zinc finger proteins contain one to six tandem CCCH motifs composed of three cysteine and one histidine residues and have been widely found in eukaryotes. Plant CCCH proteins control a wide range of developmental and adaptive processes through DNA–protein, RNA–protein and/or protein–protein interactions. The complex networks underlying these processes regulated by plant CCCH proteins are often involved in phytohormones as signal molecules. In this review, we described the evolution of CCCH proteins from green algae to vascular plants and summarized the functions of plant CCCH proteins that are influenced by six major hormones, including abscisic acid, gibberellic acid, brassinosteroid, jasmonate, ethylene and auxin. We further compared the regulatory mechanisms of plant and animal CCCH proteins via hormone signaling. Among them, Arabidopsis AtC3H14, 15 and human hTTP, three typical CCCH proteins, are able to integrate multiple hormones to participate in various biological processes.
Impact of High Glucose on Ocular Surface Glycocalyx Components: Implications for Diabetes-Associated Ocular Surface Damage
Authors: Weng Judy , Trinh Steven , Lee Rachel , Metwale Rana , Sharma Ajay
Published: November 2022

Diabetes mellitus causes several detrimental effects on the ocular surface, including compromised barrier function and an increased risk of infections. The glycocalyx plays a vital role in barrier function. The present study was designed to test the effect of a high glucose level on components of glycocalyx. Stratified human corneal and conjunctival epithelial cells were exposed to a high glucose concentration for 24 and 72 h. Changes in Mucin (MUC) 1, 4, 16 expression were quantified using real-time PCR and ELISA. Rose bengal and jacalin staining were used to assess the spatial distribution of MUC16 and O-glycosylation. Changes in the gene expression of five glycosyltransferases and forty-two proteins involved in cell proliferation and the cell cycle were also quantified using PCR and a gene array. High glucose exposure did not affect the level or spatial distribution of membrane-tethered MUC 1, 4, and 16 either in the corneal or conjunctival epithelial cells. No change in gene expression in glycosyltransferases was observed, but a decrease in the gene expression of proteins involved in cell proliferation and the cell cycle was observed. A high-glucose-mediated decrease in gene expression of proteins involved in cellular proliferation of corneal and conjunctival epithelial cells may be one of the mechanisms underlying a diabetes-associated decrease in ocular surface’s glycocalyx.
Impaired Aversive Memory Formation in GPR37L1KO Mice
Authors: Veenit Vandana , Zhang Xiaoqun , Paslawski Wojciech , Mantas Ioannis , Svenningsson Per
Published: November 2022

GPR37L1 is an orphan G-protein-coupled receptor, which is implicated in neurological disorders, but its normal physiological role is poorly understood. Its close homologue, GPR37, is implicated in Parkinson’s disease and affective disorders. In this study, we set out to characterize adult and middle-aged global GPR37L1 knock-out (KO) mice regarding emotional behaviors. Our results showed that GPR37L1KO animals, except adult GPR37L1KO males, exhibited impaired retention of aversive memory formation as assessed by the shorter retention latency in a passive avoidance task. Interestingly, the viral-mediated deletion of GPR37L1 in conditional knockout mice in the hippocampus of middle-aged mice also showed impaired retention in passive avoidance tasks, similar to what was observed in global GPR37L1KO mice, suggesting that hippocampal GPR37L1 is involved in aversive learning processes. We also observed that middle-aged GPR37L1KO male and female mice exhibited a higher body weight than their wild-type counterparts. Adult and middle-aged GPR37L1KO female mice exhibited a reduced level of serum corticosterone and middle-aged GPR37L1KO females showed a reduced level of epinephrine in the dorsal hippocampus in the aftermath of passive avoidance task, with no such effects observed in GPR37L1KO male mice, suggesting that lack of GPR37L1 influences behavior and biochemical readouts in age- and sex-specific manners.
Potent Activation of Human but Not Mouse TRPA1 by JT010
Authors: Matsubara Masaki , Muraki Yukiko , Hatano Noriyuki , Suzuki Hiroka , Muraki Katsuhiko
Published: November 2022

Transient receptor potential (TRP) ankyrin repeat 1 (TRPA1), which is involved in inflammatory pain sensation, is activated by endogenous factors, such as intracellular Zn2+ and hydrogen peroxide, and by irritant chemical compounds. The synthetic compound JT010 potently and selectively activates human TRPA1 (hTRPA1) among the TRPs. Therefore, JT010 is a useful tool for analyzing TRPA1 functions in biological systems. Here, we show that JT010 is a potent activator of hTRPA1, but not mouse TRPA1 (mTRPA1) in human embryonic kidney (HEK) cells expressing hTRPA1 and mTRPA1. Application of 0.3–100 nM of JT010 to HEK cells with hTRPA1 induced large Ca2+ responses. However, in HEK cells with mTRPA1, the response was small. In contrast, both TRPA1s were effectively activated by allyl isothiocyanate (AITC) at 10–100 μM. Similar selective activation of hTRPA1 by JT010 was observed in electrophysiological experiments. Additionally, JT010 activated TRPA1 in human fibroblast-like synoviocytes with inflammation, but not TRPA1 in mouse dorsal root ganglion cells. As cysteine at 621 (C621) of hTRPA1, a critical cysteine for interaction with JT010, is conserved in mTRPA1, we applied JT010 to HEK cells with mutations in mTRPA1, where the different residue of mTRPA1 with tyrosine at 60 (Y60), with histidine at 1023 (H1023), and with asparagine at 1027 (N1027) were substituted with cysteine in hTRPA1. However, these mutants showed low sensitivity to JT010. In contrast, the mutation of hTRPA1 at position 669 from phenylalanine to methionine (F669M), comprising methionine at 670 in mTRPA1 (M670), significantly reduced the response to JT010. Moreover, the double mutant at S669 and M670 of mTRPA1 to S669E and M670F, respectively, induced slight but substantial sensitivity to 30 and 100 nM JT010. Taken together, our findings demonstrate that JT010 potently and selectively activates hTRPA1 but not mTRPA1.
The Role of PEMFs on Bone Healing: An In Vitro Study
Authors: Caliogna Laura , Bina Valentina , Brancato Alice Maria , Gastaldi Giulia , Annunziata Salvatore , Mosconi Mario , Grassi Federico Alberto , Benazzo Francesco , Pasta Gianluigi
Published: November 2022

Bone responses to pulsed electromagnetic fields (PEMFs) have been extensively studied by using devices that expose bone cells to PEMFs to stimulate extracellular matrix (ECM) synthesis for bone and cartilage repair. The aim of this work was to highlight in which bone healing phase PEMFs exert their action. Specifically, we evaluated the effects of PEMFs both on human adipose mesenchymal stem cells (hASCs) and on primary human osteoblasts (hOBs) by testing gene and protein expression of early bone markers (on hASCs) and the synthesis of late bone-specific proteins (on hOBs) as markers of bone remodeling. Our results indicate that PEMFs seem to exert their action on bone formation, acting on osteogenic precursors (hASCs) and inducing the commitment towards the differentiation pathways, unlike mature and terminally differentiated cells (hOBs), which are known to resist homeostasis perturbation more and seem to be much less responsive than mesenchymal stem cells. Understanding the role of PEMFs on bone regenerative processes provides important details for their clinical application.
Allicin and Capsaicin Ameliorated Hypercholesterolemia by Upregulating LDLR and Downregulating PCSK9 Expression in HepG2 Cells
Authors: Nawaka Nantiya , Wanmasae Smith , Makarasen Arthit , Dechtrirat Decha , Techasakul Supanna , Jeenduang Nutjaree
Published: November 2022

Hypercholesterolemia is a common cause of cardiovascular diseases (CVDs). Although allicin and capsaicin possess hypolipidemic effects through several molecular mechanisms, their effects on LDLR and PCSK9 expression are still unknown. This study aimed to investigate the effects of allicin and capsaicin on LDLR and PCSK9 expression in HepG2 cells. The effects of allicin and capsaicin on cell viability were evaluated by MTT assay and trypan blue exclusion assay. Low-density lipoprotein receptor (LDLR) levels and LDL uptake were determined by flow cytometry and confocal laser scanning microscopy (CLSM), respectively. RT-qPCR and Western blot analyses were performed to evaluate the expression of PCSK9, LDLR, SREBP-2, and HNF1α. ELISA was used to measure PCSK9 levels in culture media. Allicin and capsaicin increased the protein expression levels of LDLR via activation of the transcription factor SREBP2. However, allicin and capsaicin decreased the expression of PCSK9 protein and the secretion of PCSK9 in culture media via the suppression of HNF1α. Moreover, allicin and capsaicin increased LDL uptake into HepG2 cells. The efficacies of the hypolipidemic effects of allicin (200 µM) and capsaicin (200 µM) were comparable to that of atorvastatin (10 µM) in this study. In conclusion, allicin and capsaicin possessed hypolipidemic effects via the upregulation of LDLR and downregulation of PCSK9 expression, thereby enhancing LDL uptake into HepG2 cells. This indicates that allicin and capsaicin should be used as potent supplements to ameliorate hypercholesterolemia.
High Instantaneous Inhibitory Potential of Bictegravir and the New Spiro-β-Lactam BSS-730A for HIV-2 Isolates from RAL-Naïve and RAL-Failing Patients
Authors: Bártolo Inês , Moranguinho Inês , Gonçalves Paloma , Diniz Ana Rita , Borrego Pedro , Martin Francisco , Figueiredo Inês , Gomes Perpétua , Gonçalves Fátima , Alves Américo J. S. , Alves Nuno , Caixas Umbelina , Pinto Inês V. , Barahona Isabel , Pinho e Melo Teresa M. V. D. , Taveira Nuno
Published: November 2022

Integrase inhibitors (INIs) are an important class of drugs for treating HIV-2 infection, given the limited number of drugs active against this virus. While the clinical efficacy of raltegravir and dolutegravir is well established, the clinical efficacy of bictegravir for treating HIV-2 infected patients has not been determined. Little information is available regarding the activity of bictegravir against HIV-2 isolates from patients failing raltegravir-based therapy. In this study, we examined the phenotypic and matched genotypic susceptibility of HIV-2 primary isolates from raltegravir-naïve and raltegravir-failing patients to raltegravir, dolutegravir, and bictegravir, and to the new spiro-β-lactam BSS-730A. The instantaneous inhibitory potential (IIP) was calculated to help predict the clinical activity of bictegravir and BSS-730A. Isolates from raltegravir-naïve patients were highly sensitive to all INIs and BSS-730A. Combined integrase mutations E92A and Q148K conferred high-level resistance to raltegravir, and E92Q and T97A conferred resistance to raltegravir and dolutegravir. The antiviral activity of bictegravir and BSS-730A was not affected by these mutations. BSS-730A displayed strong antiviral synergism with raltegravir. Mean IIP values at Cmax were similar for all INIs and were not significantly affected by resistance mutations. IIP values were significantly higher for BSS-730A than for INIs. The high IIP values of bictegravir and BSS-730A for raltegravir-naïve and raltegravir-resistant HIV-2 isolates highlight their potential value for treating HIV-2 infection. Overall, the results are consistent with the high clinical efficacy of raltegravir and dolutegravir for HIV-2 infection and suggest a promising clinical profile for bictegravir and BSS-730A.
Adaptation of Helicoverpa armigera to Soybean Peptidase Inhibitors Is Associated with the Transgenerational Upregulation of Serine Peptidases
Authors: Velasquez-Vasconez Pedro A. , Hunt Benjamin J. , Dias Renata O. , Souza Thaís P. , Bass Chris , Silva-Filho Marcio C.
Published: November 2022

Molecular phenotypes induced by environmental stimuli can be transmitted to offspring through epigenetic inheritance. Using transcriptome profiling, we show that the adaptation of Helicoverpa armigera larvae to soybean peptidase inhibitors (SPIs) is associated with large-scale gene expression changes including the upregulation of genes encoding serine peptidases in the digestive system. Furthermore, approximately 60% of the gene expression changes induced by SPIs persisted in the next generation of larvae fed on SPI-free diets including genes encoding regulatory, oxidoreductase, and protease functions. To investigate the role of epigenetic mechanisms in regulating SPI adaptation, the methylome of the digestive system of first-generation larvae (fed on a diet with and without SPIs) and of the progeny of larvae exposed to SPIs were characterized. A comparative analysis between RNA-seq and Methyl-seq data did not show a direct relationship between differentially methylated and differentially expressed genes, while trypsin and chymotrypsin genes were unmethylated in all treatments. Rather, DNA methylation potential epialleles were associated with transcriptional and translational controls; these may play a regulatory role in the adaptation of H. armigera to SPIs. Altogether, our findings provided insight into the mechanisms of insect adaptation to plant antiherbivore defense proteins and illustrated how large-scale transcriptional reprograming of insect genes can be transmitted across generations.
Restraint Stress and Repeated Corticosterone Administration Differentially Affect Neuronal Excitability, Synaptic Transmission and 5-HT7 Receptor Reactivity in the Dorsal Raphe Nucleus of Young Adult Male Rats
Authors: Bąk Joanna , Bobula Bartosz , Hess Grzegorz
Published: November 2022

Exogenous corticosterone administration reduces GABAergic transmission and impairs its 5-HT7 receptor-dependent modulation in the rat dorsal raphe nucleus (DRN), but it is largely unknown how neuronal functions of the DRN are affected by repeated physical and psychological stress. This study compared the effects of repeated restraint stress and corticosterone injections on DRN neuronal excitability, spontaneous synaptic transmission, and its 5-HT7 receptor-dependent modulation. Male Wistar rats received corticosterone injections for 7 or 14 days or were restrained for 10 min twice daily for 3 days. Repeated restraint stress and repeated corticosterone administration evoked similar changes in performance in the forced swim test. They increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) recorded from DRN neurons. In contrast to the treatment with corticosterone, restraint stress-induced changes in sEPSC kinetics and decreased intrinsic excitability of DRN neurons did not modify inhibitory transmission. Repeated injections of the 5-HT7 receptor antagonist SB 269970 ameliorated the effects of restraint on excitability and sEPSC frequency but did not restore the altered kinetics of sEPSCs. Thus, repeated restraint stress and repeated corticosterone administration differ in consequences for the intrinsic excitability of DRN projection neurons and their excitatory and inhibitory synaptic inputs. Effects of repeated restraint stress on DRN neurons can be partially abrogated by blocking the 5-HT7 receptor.
Advances in the Current Understanding of the Role of Extracellular Vesicles in Allergy, Autoimmunity and Immune Regulation
Authors: Bryniarski Krzysztof , Nazimek Katarzyna
Published: November 2022

Cells release extracellular vesicles (EVs), such as exosomes and microvesicles, both under physiological and pathological conditions, making EV-dependent signaling cascades a very precise system of intercellular communication [...]
Gotta Go Slow: Two Evolutionarily Distinct Annelids Retain a Common Hedgehog Pathway Composition, Outlining Its Pan-Bilaterian Core
Authors: Platova Sofia , Poliushkevich Liudmila , Kulakova Milana , Nesterenko Maksim , Starunov Viktor , Novikova Elena
Published: November 2022

Hedgehog signaling is one of the key regulators of morphogenesis, cell differentiation, and regeneration. While the Hh pathway is present in all bilaterians, it has mainly been studied in model animals such as Drosophila and vertebrates. Despite the conservatism of its core components, mechanisms of signal transduction and additional components vary in Ecdysozoa and Deuterostomia. Vertebrates have multiple copies of the pathway members, which complicates signaling implementation, whereas model ecdysozoans appear to have lost some components due to fast evolution rates. To shed light on the ancestral state of Hh signaling, models from the third clade, Spiralia, are needed. In our research, we analyzed the transcriptomes of two spiralian animals, errantial annelid Platynereis dumerilii (Nereididae) and sedentarian annelid Pygospio elegans (Spionidae). We found that both annelids express almost all Hh pathway components present in Drosophila and mouse. We performed a phylogenetic analysis of the core pathway components and built multiple sequence alignments of the additional key members. Our results imply that the Hh pathway compositions of both annelids share more similarities with vertebrates than with the fruit fly. Possessing an almost complete set of single-copy Hh pathway members, lophotrochozoan signaling composition may reflect the ancestral features of all three bilaterian branches.
Immunization of Mice with Gold Nanoparticles Conjugated to Thermostable Cancer Antigens Prevents the Development of Xenografted Tumors
Authors: Dykman Lev A. , Staroverov Sergey A. , Kozlov Sergey V. , Fomin Alexander S. , Chumakov Daniil S. , Gabalov Konstantin P. , Kozlov Yevgeny S. , Soldatov Dmitry A. , Khlebtsov Nikolai G.
Published: November 2022

Gold nanoparticles as part of vaccines greatly increase antigen stability, antigen accumulation in the lymph nodes, and antigen uptake by antigen-presenting cells. The use of such particles as part of anticancer vaccines based on heat shock proteins to increase vaccine effectiveness is timely. We prepared and characterized nanoconjugates based on 15-nm gold nanoparticles and thermostable tumor antigens isolated from MH22a murine hepatoma cells. The whole-cell lysate of MH22a cells contained the main heat shock proteins. BALB/c mice were injected with the conjugates and then received transplants of MH22a cells. The highest titer was produced in mice immunized with the complex of gold nanoparticles + antigen with complete Freund’s adjuvant. The immunized mice showed no signs of tumor growth for 24 days. They also showed a decreased production of the INF-γ, IL-6, and IL-1 proinflammatory cytokines compared to the mice immunized through other schemes. This study is the first to show that it is possible in principle to use gold nanoparticles in combination with thermostable tumor antigens for antitumor vaccination. Antitumor vaccines based on thermostable tumor antigens can be largely improved by including gold nanoparticles as additional adjuvants.
Can Citizenship Education Benefit Computing?
Authors: Connolly Randy
Published: November 2022

A recurring motif in recent scholarship in the computing ethics and society studies (CESS) subfield within computing have been the calls for a wider recognition of the social and political nature of computing work. These calls have highlighted the limitations of an ethics-only approach to covering social and political topics such as bias, fairness, equality, and justice within computing curricula. However, given the technically focused background of most computing educators, it is not necessarily clear how political topics should best be addressed in computing courses. This paper proposes that one helpful way to do so is via the well-established pedagogy of citizenship education, and as such it endeavors to introduce the discourse of citizenship education to an audience of computing educators. In particular, the change within citizenship education away from its early focus on personal responsibility and duty to its current twin focus on engendering civic participation in one’s community along with catalyzing critical attitudes to the realities of today’s social, political, and technical worlds, is especially relevant to computing educators in light of computing’s new-found interest in the political education of its students. Related work in digital literacy education is also discussed.
Multi-Objective Optimization of Base-Isolated Tanks with Supplemental Linear Viscous Dampers
Authors: Tsipianitis Alexandros , Tsompanakis Yiannis
Published: November 2022

Base isolation of liquid storage tanks has proven to be an efficient seismic protection measure, leading to a drastic reduction of a superstructure’s distress. However, many such tanks are located near seismic tectonic faults, which generate strong pulse-like ground motions that can impose excessive displacement demands on the isolators. For this reason, viscous dampers are incorporated into the isolation system to avoid overconservative isolators design. To optimize the seismic performance of hybrid isolation systems consisting of single friction pendulum bearings and linear viscous dampers, two novel multi-objective optimization approaches are proposed in the current study. Furthermore, suitable constraint functions and design variables are selected, considering the most critical parameters of the hybrid isolation system. The multi-objective genetic algorithm optimizer is used for the solution of both problems. The results are presented in the typical form of Pareto and certain optimal design solutions are carefully chosen and compared in terms of isolators fragility curves and tank accelerations. The main aim is to optimize the critical design parameters by achieving a reasonable balance among contradicting objectives. The tank industry can substantially benefit from this study, as a more cost-efficient design of hybrid base-isolation can be attained for large-scale tanks.
Electrodeposited PPy@TiO2 and PEDOT@TiO2 Counter Electrodes for [Co(bpy)3]2+/3+ Redox Mediator-Based Dye-Sensitized Solar Cells
Authors: Ahmed Abdelaal S. A. , Yi Xie , Zhao Xiujian , Xiang Wanchun , Abdelmotallieb Mohammed
Published: November 2022

The main goal of this work is to enhance the catalytic performance of PPy and PEDOT films toward the Co2+/Co3+ redox couple. PPy and PEDOT films were electrodeposited separately on a porous TiO2 template to assess their suitability as alternative catalysts in dye-sensitized solar cells (DSSC) based on the [Co(bpy)3]2+/3+ redox shuttle. The obtained PPy@TiO2 and PEDOT@TiO2 counter electrodes displayed much rougher surfaces. Electrochemical studies indicate the superior catalytic activity of both the electrodeposited electrodes toward Co3+ reduction, as indicated by lower charge transfer resistance than that of pristine films and even that of Pt electrodes. Therefore, the fabricated DSSC devices with these counter electrodes achieved higher power conversion efficiencies compared to cells with pristine PPy and PEDOT counter electrodes, or even with a Pt counter electrode. Interestingly, the assembled DSSC device with a PEDOT@TiO2 counter electrode displayed the highest performance among all with a power conversion efficiency of 6.62%, which is better than that obtained by the device with a Pt electrode (6.07%).
Distribution of Insecticide Resistance Genetic Markers in the West Nile Virus Vector Culex pipiens from South-Eastern Romania
Authors: Stancu Ioana Georgeta , Prioteasa Florian Liviu , Tiron Georgiana Victorița , Cotar Ani Ioana , Fălcuță Elena , Porea Daniela , Dinu Sorin , Ceianu Cornelia Svetlana , Csutak Ortansa
Published: November 2022

Culex pipiens pipiens and Culex pipiens molestus mosquitoes are the vectors of West Nile virus in south-eastern Romania, an area of intense circulation and human transmission of this virus. The level of insecticide resistance for the mosquito populations in the region has not been previously assessed. Culex pipiens mosquitoes collected between 2018 and 2019 in south-eastern Romania from different habitats were subjected to biotype identification by real-time PCR. Substitutions causing resistance to organophosphates and carbamates (F290V and G119S in acetylcholinesterase 1) and to pyrethroids (L1014F in voltage gated Na+ channel) were screened by PCR or sequencing. Substitutions F290V and G119S were detected at very low frequencies and only in heterozygous state in Culex pipiens molestus biotype specimens collected in urban areas. The molestus biotype population analysed was entirely homozygous for L1014F, and high frequencies of this substitution were also found for pipiens biotype and hybrid mosquitoes collected in urban and in intensive agriculture areas. Reducing the selective pressure by limiting the use of pyrethroid insecticides only for regions where it is absolutely necessary and monitoring L1014F mutation should be taken into consideration when implementing vector control strategies.
A New Genus and Species of the Suborder Trogiomorpha (Insecta, Psocodea) from Mid-Cretaceous Amber of Myanmar
Authors: Zhang Xinyi , Liang Feiyang , Liu Xingyue
Published: November 2022

We established a new genus with a new species Brachyantennum spinosum Liang et Liu, gen. et sp. nov. from mid-Cretaceous Burmese Kachin amber. It is tentatively placed into the suborder Trogiomorpha, based on the strong external valve, the reduced dorsal and ventral valve, and the short subgenital plate covering the basal part of the external valve. This new genus is apparently close to the family Cormopsocidae, based on the well-developed and very long hindwing Sc vein. However, its familial placement is ambiguous and it can be excluded from the established families of Trogiomorpha by the presence of the tarsal ctenidiobothria on the mid- and hindleg.
Evaluation of the Operating Modes of the Urban Electric Networks in Dushanbe City, Tajikistan
Authors: Tavarov Saidjon Shiralievich , Zicmane Inga , Beryozkina Svetlana , Praveenkumar Seepana , Safaraliev Murodbek , Shonazarova Shahnoza
Published: November 2022

Currently, energy saving has become an acute problem all over the world. Due to the rapid development of both the energy and information technology sectors, as well as an increase in the electricity demand, the electric distribution system is facing problems caused by stricter requirements for electricity quality, reliability, efficiency, and sustainability. Therefore, the use of energy-saving technologies, both the improvement of existing ones and the application of new ones, is one of the main reserves for electricity saving in power supply systems. This study is devoted to the evaluation of the operating modes of transformer substations of the 6–10 kV electric distribution network in Dushanbe city, based on the results of control winter measurements and the dependence of the low coefficient of active power in transformer substations. It has been observed that, with a low coefficient of active power in transformer substations, when transmitting electricity from substation busbars to transformer substations of a final consumer via overhead transmission lines (an average length of 5 km), the voltage loss exceeds the maximum permissible values. When transmitting electricity via cable lines, the voltage losses are within the limit of 5%. However, a low active power factor may be the reason for an increase in capacitive currents, followed by the command of single-phase earth fault currents. Due to the low active power factor, the increase in voltage losses and useful power losses leads to the inefficient operating modes of the transformer substations.
Relationship between the Hemoglobin-to-Red Cell Distribution Width Ratio and All-Cause Mortality in Septic Patients with Atrial Fibrillation: Based on Propensity Score Matching Method
Authors: Wang Junhong , Chen Zirong , Yang Hongkuan , Li Hua , Chen Rudong , Yu Jiasheng
Published: November 2022

(1) Objective: To reveal the correlation between the hemoglobin-to-red cell distribution width ratio (HRR) and all-cause mortality (ACM) among the septic patients with atrial fibrillation. (2) Methods: Specific clinical information was collected from the Medical Information Mart for Intensive IV (MIMIC-IV) database. The optimal cut-off value of HRR was calculated through ROC curve analysis conducted by using the maximum Youden index for the prediction of survival status. In addition, univariable and multivariable Cox regressive analyses were carried out to assess the prognostic significance of HRR and the Kaplan-Meier (K-M) analysis was conducted to draw the survival curves. Then, the 1:1 propensity score matching (PSM) method was adopted to improve the reliability of research result while balancing the unintended influence of underlying confounders. (3) Results: There were 9228 patients participating in this retrospective cohort study. The optimal cut-off value of the HRR was determined as 5.877 for in-hospital mortality. The PSM was performed to identify 2931 pairs of score-matched patients, with balanced differences exhibited by nearly all variables. According to the K-M analysis, those patients with a lower HRR than 5.877 showed a significantly higher level of in-hospital mortality, 28-day mortality, and 90-day mortality, compared to the patients with HRR ≥ 5.877 (p < 0.001). After the adjustment of possible confounders, those patients whose HRR was below 5.877 had a significantly higher level of in-hospital mortality than the patients with HRR ≥ 5.877, as revealed by the multivariable Cox regression analysis (HR = 1.142, 95%CI: 1.210–1.648, p < 0.001). Similarly, the ACM remained substantially higher in those patients with a lower HRR than in the patients with higher HRR after PSM. (4) Conclusion: A lower HRR (<5.877) was evidently associated with an increased risk of ACM, which made it applicable as a prognostic predictor of clinical outcomes for those septic patients with atrial fibrillation.
Towards a More Individually Tailored Exercise Prescription for Promoting Cardiovascular Health
Authors: Caminiti Giuseppe , Iellamo Ferdinando
Published: November 2022

The beneficial effects of exercise training (ET) in promoting cardiovascular health have been well established [...]
Effect of Portable, In-Hospital Extracorporeal Membrane Oxygenation on Clinical Outcomes
Authors: Ciullo Anna L. , Wall Natalie , Taleb Iosif , Koliopoulou Antigone , Stoddard Kathleen , Drakos Stavros G. , Welt Fred G. , Goodwin Matthew , Van Dyk Nate , Kagawa Hiroshi , McKellar Stephen H. , Selzman Craig H. , Tonna Joseph E.
Published: November 2022

The time between onset of cardiogenic shock and initiation of mechanical circulatory support is inversely related to patient survival as delays in transporting patients to the operating room (OR) for venoarterial extracorporeal membrane oxygenation (VA ECMO) could prove fatal. A primed and portable VA ECMO system may allow faster initiation of ECMO in various hospital locations and subsequently improve outcomes for patients in cardiogenic shock. We reviewed our institutional experience with VA ECMO based on two time periods: beginning of our VA ECMO program and from initiation of our primed and portable in-hospital ECMO system. The primary endpoint was patient survival to discharge. A total of 137 patients were placed on VA ECMO during the study period; n = 66 (48%) before and n = 71 (52%) after program initiation. In the second era, the proportion of OR ECMO initiation decreased significantly (from 92% to 49%, p < 0.01) as more patients received ECMO in other hospital units, including the emergency department (p < 0.01) and during cardiac arrest (12% vs. 38%, p < 0.01). Survival to hospital discharge was equivalent between the two groups (30% vs. 42%, p = 0.1) despite more patients being placed on ECMO during ongoing cardiac arrest. Finally, we observed increased clinical volume since initiation of the in-hospital, portable ECMO system. Developing an in-hospital, primed and portable VA ECMO program resulted in increased clinical volume with equivalent patient survival despite a sicker cohort of patients. We conclude that more rapid deployment of VA ECMO may extend the treatment eligibility to more patients and improve patient outcomes.
Identification of the Optimal Position of a Nasal Oxygen Cannula for Apneic Oxygenation: A Technical Simulation
Authors: Wetsch Wolfgang , Schroeder Daniel , Herff Susanne , Böttiger Bernd , Wenzel Volker , Herff Holger
Published: November 2022

Background: In a cannot-ventilate-cannot-intubate situation, careful preoxygenation with high FiO2 allowing subsequent apneic oxygenation can be life-saving. The best position for an oxygen supply line within the human airway at which oxygen insufflation is more effective than standard preoxygenation with a face mask is unknown. Methods: In this experimental study, we compared the effectiveness of preoxygenation by placing an oxygen cannula at the nose entrance, through the nose at the soft palatine, or at the base of the tongue; as a control we used ambient air. We connected a fully preoxygenated test lung on one side to an oximeter with a flow rate of 200 mL/min simulating the oxygen consumption of a normal adult on the other side of the trachea of an anatomically correctly shaped airway manikin over a 20 min observation period five times for each cannula placement in a random order. Results: The oxygen percentage in the test lung dropped from 100% in all groups to 53 ± 1% in the ambient air control group, to 87 ± 2% in the nasal cannula group, and to 96 ± 2% in the soft palatine group; it remained at 99 ± 1% in the base of the tongue group (p = 0.003 for the soft palatine vs. base of the tongue and p < 0.001 for all other groups). Conclusions: When simulating apneic oxygenation in a preoxygenated manikin, oxygen insufflation at the base of the tongue kept the oxygen percentage at baseline values of 99%, demonstrating a complete block of ambient air flowing into the airway of the manikin. Oxygen insufflation at the soft palatine or insufflation via a nasal cannula were less effective regarding this effect.