bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic Modifications and Non-Coding RNA in Diabetes-Mellitus-Induced Coronary Artery Disease: Pathophysiological Link and New Therapeutic Frontiers
Authors: Prandi Francesca Romana , Lecis Dalgisio , Illuminato Federica , Milite Marialucia , Celotto Roberto , Lerakis Stamatios , Romeo Francesco , Barillà Francesco
Published: April 2022

Diabetes mellitus (DM) is a glucose metabolism disorder characterized by chronic hyperglycemia resulting from a deficit of insulin production and/or action. DM affects more than 1 in 10 adults, and it is associated with an increased risk of cardiovascular morbidity and mortality. Cardiovascular disease (CVD) accounts for two thirds of the overall deaths in diabetic patients, with coronary artery disease (CAD) and ischemic cardiomyopathy as the main contributors. Hyperglycemic damage on vascular endothelial cells leading to endothelial dysfunction represents the main initiating factor in the pathogenesis of diabetic vascular complications; however, the underlying pathophysiological mechanisms are still not entirely understood. This review addresses the current knowledge on the pathophysiological links between DM and CAD with a focus on the role of epigenetic modifications, including DNA methylation, histone modifications and noncoding RNA control. Increased knowledge of epigenetic mechanisms has contributed to the development of new pharmacological treatments (“epidrugs”) with epigenetic targets, although these approaches present several challenges. Specific epigenetic biomarkers may also be used to predict or detect the development and progression of diabetes complications. Further studies on diabetes and CAD epigenetics are needed in order to identify possible new therapeutic targets and advance personalized medicine with the prediction of individual drug responses and minimization of adverse effects.
Integrative Physiological and Transcriptomic Analysis Reveals the Transition Mechanism of Sugar Phloem Unloading Route in Camellia oleifera Fruit
Authors: Zhou Jing , Du Bingshuai , Chen Yuqing , Cao Yibo , Yu Mingxin , Zhang Lingyun
Published: April 2022

Sucrose phloem unloading plays a vital role in photoassimilate distribution and storage in sink organs such as fruits and seeds. In most plants, the phloem unloading route was reported to shift between an apoplasmic and a symplasmic pattern with fruit development. However, the molecular transition mechanisms of the phloem unloading pathway still remain largely unknown. In this study, we applied RNA sequencing to profile the specific gene expression patterns for sucrose unloading in C. oleifera fruits in the apo- and symplasmic pathways that were discerned by CF fluoresce labelling. Several key structural genes were identified that participate in phloem unloading, such as PDBG11, PDBG14, SUT8, CWIN4, and CALS10. In particular, the key genes controlling the process were involved in callose metabolism, which was confirmed by callose staining. Based on the co-expression network analysis with key structural genes, a number of transcription factors belonging to the MYB, C2C2, NAC, WRKY, and AP2/ERF families were identified to be candidate regulators for the operation and transition of phloem unloading. KEGG enrichment analysis showed that some important metabolism pathways such as plant hormone metabolism, starch, and sucrose metabolism altered with the change of the sugar unloading pattern. Our study provides innovative insights into the different mechanisms responsible for apo- and symplasmic phloem unloading in oil tea fruit and represents an important step towards the omics delineation of sucrose phloem unloading transition in crops.
Mechanisms Underlying Soybean Response to Phosphorus Deficiency through Integration of Omics Analysis
Authors: Mo Xiaohui , Liu Guoxuan , Zhang Zeyu , Lu Xing , Liang Cuiyue , Tian Jiang
Published: April 2022

Low phosphorus (P) availability limits soybean growth and yield. A set of potential strategies for plant responses to P deficiency have been elucidated in the past decades, especially in model plants such as Arabidopsis thaliana and rice (Oryza sativa). Recently, substantial efforts focus on the mechanisms underlying P deficiency improvement in legume crops, especially in soybeans (Glycine max). This review summarizes recent advances in the morphological, metabolic, and molecular responses of soybean to phosphate (Pi) starvation through the combined analysis of transcriptomics, proteomics, and metabolomics. Furthermore, we highlight the functions of the key factors controlling root growth and P homeostasis, base on which, a P signaling network in soybean was subsequently presumed. This review also discusses current barriers and depicts perspectives in engineering soybean cultivars with high P efficiency.
The Regulatory Roles of Intrinsically Disordered Linker in VRN1-DNA Phase Separation
Authors: Huang Qiaojing , Wang Yanyan , Liu Zhirong , Lai Luhua
Published: April 2022

Biomacromolecules often form condensates to function in cells. VRN1 is a transcriptional repressor that plays a key role in plant vernalization. Containing two DNA-binding domains connected by an intrinsically disordered linker (IDL), VRN1 was shown to undergo liquid-like phase separation with DNA, and the length and charge pattern of IDL play major regulatory roles. However, the underlying mechanism remains elusive. Using a polymer chain model and lattice-based Monte-Carlo simulations, we comprehensively investigated how the IDL regulates VRN1 and DNA phase separation. Using a worm-like chain model, we showed that the IDL controls the binding affinity of VRN1 to DNA, by modulating the effective local concentration of the VRN1 DNA-binding domains. The predicted binding affinities, under different IDL lengths, were in good agreement with previously reported experimental results. Our simulation of the phase diagrams of the VRN1 variants with neutral IDLs and DNA revealed that the ability of phase separation first increased and then decreased, along with the increase in the linker length. The strongest phase separation ability was achieved when the linker length was between 40 and 80 residues long. Adding charged patches to the IDL resulted in robust phase separation that changed little with IDL length variations. Our study provides mechanism insights on how IDL regulates VRN1 and DNA phase separation, and why naturally occurring VRN1-like proteins evolve to contain the charge segregated IDL sequences, which may also shed light on the molecular mechanisms of other IDL-regulated phase separation processes in living cells.
Biocompatibility and Mechanical Stability of Nanopatterned Titanium Films on Stainless Steel Vascular Stents
Authors: Yelkarasi Cagatay , Recek Nina , Kazmanli Kursat , Kovač Janez , Mozetič Miran , Urgen Mustafa , Junkar Ita
Published: April 2022

Nanoporous ceramic coatings such as titania are promoted to produce drug-free cardiovascular stents with a low risk of in-stent restenosis (ISR) because of their selectivity towards vascular cell proliferation. The brittle coatings applied on stents are prone to cracking because they are subjected to plastic deformation during implantation. This study aims to overcome this problem by using a unique process without refraining from biocompatibility. Accordingly, a titanium film with 1 µm thickness was deposited on 316 LVM stainless-steel sheets using magnetron sputtering. Then, the samples were anodized to produce nanoporous oxide. The nanoporous oxide was removed by ultrasonication, leaving an approximately 500 nm metallic titanium layer with a nanopatterned surface. XPS studies revealed the presence of a 5 nm-thick TiO2 surface layer with a trace amount of fluorinated titanium on nanopatterned surfaces. Oxygen plasma treatment of the nanopatterned surface produced an additional 5 nm-thick fluoride-free oxide layer. The samples did not exhibit any cracking or spallation during plastic deformation. Cell viability studies showed that nanopatterned surfaces stimulate endothelial cell proliferation while reducing the proliferation of smooth muscle cells. Plasma treatment further accelerated the proliferation of endothelial cells. Activation of blood platelets did not occur on oxygen plasma-treated, fluoride-free nanopatterned surfaces. The presented surface treatment method can also be applied to other stent materials such as CoCr, nitinol, and orthopedic implants.
Inflammation: A New Look at an Old Problem
Authors: Gusev Evgenii , Zhuravleva Yulia
Published: April 2022

Pro-inflammatory stress is inherent in any cells that are subject to damage or threat of damage. It is defined by a number of universal components, including oxidative stress, cellular response to DNA damage, unfolded protein response to mitochondrial and endoplasmic reticulum stress, changes in autophagy, inflammasome formation, non-coding RNA response, formation of an inducible network of signaling pathways, and epigenetic changes. The presence of an inducible receptor and secretory phenotype in many cells is the cause of tissue pro-inflammatory stress. The key phenomenon determining the occurrence of a classical inflammatory focus is the microvascular inflammatory response (exudation, leukocyte migration to the alteration zone). This same reaction at the systemic level leads to the development of life-critical systemic inflammation. From this standpoint, we can characterize the common mechanisms of pathologies that differ in their clinical appearance. The division of inflammation into alternative variants has deep evolutionary roots. Evolutionary aspects of inflammation are also described in the review. The aim of the review is to provide theoretical arguments for the need for an up-to-date theory of the relationship between key human pathological processes based on the integrative role of the molecular mechanisms of cellular and tissue pro-inflammatory stress.
Shortened Infant Telomere Length Is Associated with Attention Deficit/Hyperactivity Disorder Symptoms in Children at Age Two Years: A Birth Cohort Study
Authors: Pham Cindy , Vryer Regan , O’Hely Martin , Mansell Toby , Burgner David , Collier Fiona , Symeonides Christos , Tang Mimi L. K. , Vuillermin Peter , Gray Lawrence , Saffery Richard , Ponsonby Anne-Louise ,   on behalf of the Barwon Infant Study Investigator Group
Published: April 2022

Environmental factors can accelerate telomere length (TL) attrition. Shortened TL is linked to attention deficit/hyperactivity disorder (ADHD) symptoms in school-aged children. The onset of ADHD occurs as early as preschool-age, but the TL-ADHD association in younger children is unknown. We investigated associations between infant TL and ADHD symptoms in children and assessed environmental factors as potential confounders and/or mediators of this association. Relative TL was measured by quantitative polymerase chain reaction in cord and 12-month blood in the birth cohort study, the Barwon Infant Study. Early life environmental factors collected antenatally to two years were used to measure confounding. ADHD symptoms at age two years were evaluated by the Child Behavior Checklist Attention Problems (AP) and the Attention Deficit/Hyperactivity Problems (ADHP). Associations between early life environmental factors on TL or ADHD symptoms were assessed using multivariable regression models adjusted for relevant factors. Telomere length at 12 months (TL12), but not at birth, was inversely associated with AP (β = −0.56; 95% CI (−1.13, 0.006); p = 0.05) and ADHP (β = −0.66; 95% CI (−1.11, −0.21); p = 0.004). Infant secondhand smoke exposure at one month was independently associated with shorter TL12 and also higher ADHD symptoms. Further work is needed to elucidate the mechanisms that influence TL attrition and early neurodevelopment.
NMR Characterization of Long-Chain Fatty Acylcarnitine Binding to the Mitochondrial Carnitine/Acylcarnitine Carrier
Authors: Zhang Ningning , Jia Xiaopu , Fan Shuai , Wu Bin , Wang Shuqing , OuYang Bo
Published: April 2022

The mitochondrial carnitine/acylcarnitine carrier (CAC) transports short-, medium- and long-carbon chain acylcarnitines across the mitochondrial inner membrane in exchange for carnitine. How CAC recognizes the substrates with various fatty acyl groups, especially long-chain fatty acyl groups, remains unclear. Here, using nuclear magnetic resonance (NMR) technology, we have shown that the CAC protein reconstituted into a micelle system exhibits a typical six transmembrane structure of the mitochondrial carrier family. The chemical shift perturbation patterns of different fatty acylcarnitines suggested that the segment A76–G81 in CAC specifically responds to the long-chain fatty acylcarnitine. Molecular dynamics (MD) simulations of palmitoyl-L-carnitine inside the CAC channel showed the respective interaction and motion of the long-chain acylcarnitine in CAC at the cytosol-open state and matrix-open state. Our data provided a molecular-based understanding of CAC structure and transport mechanism.
Isolation of Potato Endophytes and Screening of Chaetomium globosum Antimicrobial Genes
Authors: Zhang Jiaxin , Islam Md. Samiul , Wang Jieyu , Zhao Yang , Dong Wubei
Published: April 2022

Antimicrobial peptides (AMPs) have natural antibacterial activities that pathogens find difficult to overcome. As a result of this occurrence, AMPs can act as an important substitute against the microbial resistance. In this study, we used plate confrontation tests to screen out 20 potential endophytes from potato tubers. Among them, endophyte F5 was found to significantly inhibit the growth of five different pathogenic fungi. Following that, phylogenetic analysis revealed that the internal transcribed spacer (ITS) sequences were 99% identical to Chaetomium globosum corresponding sequences. Thereafter, the Bacillus subtilis expression system was used to create a C. globosum cDNA library in order to isolate the resistance genes. Using this approach, the resistance gene screening technology in the indicator bacteria built-in library was used to identify two antimicrobial peptides, CgR2150 and CgR3101, with broad-spectrum antibacterial activities. Furthermore, the results showed that CgR2150 and CgR3101 have excellent UV, thermal, and enzyme stabilities. Also, these two peptides can significantly inhibit the growth of various bacteria (Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicola, Clavibacter michiganensis, and Clavibacter fangii) and fungi (Fusarium graminearum, Rhizoctonia solani, and Botrytis cinerea). Scanning electron microscopy (SEM) observations revealed that CgR2150 and CgR3101 peptides act against bacteria by disrupting bacterial cell membranes. Moreover, hemolytic activity assay showed that neither of the two peptides exhibited significant hemolytic activity. To conclude, the antimicrobial peptides CgR2150 and CgR3101 are promising in the development of a new antibacterial agent and for application in plant production.
Hypoxia Regulates the Self-Renewal of Endometrial Mesenchymal Stromal/Stem-like Cells via Notch Signaling
Authors: Zhang Sisi , Chan Rachel W.S. , Ng Ernest H.Y. , Yeung William S.B.
Published: April 2022

Human endometrium is an incredibly dynamic tissue undergoing cyclic regeneration and shedding during a woman’s reproductive life. Endometrial mesenchymal stromal/stem-like cells (eMSC) contribute to this process. A hypoxic niche with low oxygen levels has been reported in multiple somatic stem cell types. However, the knowledge of hypoxia on eMSC remains limited. In mice, stromal stem/progenitor cells can be identified by the label-retaining technique. We examined the relationship between the label-retaining stromal cells (LRSC) and hypoxia during tissue breakdown in a mouse model of simulated menses. Our results demonstrated that LRSC resided in a hypoxic microenvironment during endometrial breakdown and early repair. Immunofluorescence staining revealed that the hypoxic-located LRSC underwent proliferation and was highly colocalized with Notch1. In vitro studies illustrated that hypoxia activated Notch signaling in eMSC, leading to enhanced self-renewal, clonogenicity and proliferation of cells. More importantly, HIF-1α played an essential role in the hypoxia-mediated maintenance of eMSC through the activation of Notch signaling. In conclusion, our findings show that some endometrial stem/progenitor cells reside in a hypoxic niche during menstruation, and hypoxia can regulate the self-renewal activity of eMSC via Notch signaling.
Role of Polyamine-Induced Dimerization of Antizyme in Its Cellular Functions
Authors: Hyvönen Mervi T. , Smirnova Olga A. , Mitkevich Vladimir A. , Tunitskaya Vera L. , Khomutov Maxim , Karpov Dmitry S. , Korolev Sergey P. , Häkkinen Merja R. , Pietilä Marko , Gottikh Marina B. , Vepsäläinen Jouko , Alhonen Leena , Makarov Alexander A. , Kochetkov Sergey N. , Wallace Heather M. , Keinänen Tuomo A. , Khomutov Alex R.
Published: April 2022

The polyamines, spermine (Spm) and spermidine (Spd), are important for cell growth and function. Their homeostasis is strictly controlled, and a key downregulator of the polyamine pool is the polyamine-inducible protein, antizyme 1 (OAZ1). OAZ1 inhibits polyamine uptake and targets ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine biosynthesis, for proteasomal degradation. Here we report, for the first time, that polyamines induce dimerization of mouse recombinant full-length OAZ1, forming an (OAZ1)2-Polyamine complex. Dimerization could be modulated by functionally active C-methylated spermidine mimetics (MeSpds) by changing the position of the methyl group along the Spd backbone—2-MeSpd was a poor inducer as opposed to 1-MeSpd, 3-MeSpd, and Spd, which were good inducers. Importantly, the ability of compounds to inhibit polyamine uptake correlated with the efficiency of the (OAZ1)2-Polyamine complex formation. Thus, the (OAZ1)2-Polyamine complex may be needed to inhibit polyamine uptake. The efficiency of polyamine-induced ribosomal +1 frameshifting of OAZ1 mRNA could also be differentially modulated by MeSpds—2-MeSpd was a poor inducer of OAZ1 biosynthesis and hence a poor downregulator of ODC activity unlike the other MeSpds. These findings offer new insight into the OAZ1-mediated regulation of polyamine homeostasis and provide the chemical tools to study it.
The P2X7 Receptor Promotes Colorectal Inflammation and Tumorigenesis by Modulating Gut Microbiota and the Inflammasome
Authors: Bernardazzi Claudio , Castelo-Branco Morgana Teixeira Lima , Pêgo Beatriz , Ribeiro Beatriz Elias , Rosas Siane Lopes Bittencourt , Santana Patrícia Teixeira , Machado João Carlos , Leal Camille , Thompson Fabiano , Coutinho-Silva Robson , de Souza Heitor Siffert Pereira
Published: April 2022

Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). Methods: CA-CRC was induced in P2X7R+/+ and P2X7R−/− mice with azoxymethane (AOM) combined with dextran sodium sulfate (DSS). In a therapeutic protocol, P2X7R+/+ mice were treated with a P2X7R-selective inhibitor (A740003). Mice were evaluated with follow-up video endoscopy with endoluminal ultrasound biomicroscopy. Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. Results: The P2X7R+/+ mice displayed more ulcers, tumors, and greater wall thickness, than the P2X7R−/− and the P2X7R+/+ mice treated with A740003. The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. Microbial changes were observed in the P2X7R−/− and P2X7R+/+-induced mice, partially reversed by the A740003 treatment. Conclusions: Regulatory mechanisms activated downstream of the P2X7R in combination with signals from a dysbiotic microbiota result in the activation of intracellular signaling pathways and the inflammasome, amplifying the inflammatory response and promoting CA-CRC development.
Acute T-Cell-Driven Inflammation Requires the Endoglycosidase Heparanase-1 from Multiple Cell Types
Authors: Wu Zuopeng , Sweet Rebecca A. , Hoyne Gerard F. , Simeonovic Charmaine J. , Parish Christopher R.
Published: April 2022

It has been accepted for decades that T lymphocytes and metastasising tumour cells traverse basement membranes (BM) by deploying a battery of degradative enzymes, particularly proteases. However, since many redundant proteases can solubilise BM it has been difficult to prove that proteases aid cell migration, particularly in vivo. Recent studies also suggest that other mechanisms allow BM passage of cells. To resolve this issue we exploited heparanase-1 (HPSE-1), the only endoglycosidase in mammals that digests heparan sulfate (HS), a major constituent of BM. Initially we examined the effect of HPSE-1 deficiency on a well-characterised adoptive transfer model of T-cell-mediated inflammation. We found that total elimination of HPSE-1 from this system resulted in a drastic reduction in tissue injury and loss of target HS. Subsequent studies showed that the source of HPSE-1 in the transferred T cells was predominantly activated CD4+ T cells. Based on bone marrow chimeras, two cellular sources of HPSE-1 were identified in T cell recipients, one being haematopoiesis dependent and the other radiation resistant. Collectively our findings unequivocally demonstrate that an acute T-cell-initiated inflammatory response is HPSE-1 dependent and is reliant on HPSE-1 from at least three different cell types.
Molecular Cytogenetic and Physiological Characterization of a Novel Wheat-Rye T1RS.1BL Translocation Line from Secale cereal L. Weining with Resistance to Stripe Rust and Functional “Stay Green” Trait
Authors: Li Zhi , Jiang Qing , Fan Tao , Zhao Liqi , Ren Zhenglong , Tan Feiquan , Luo Peigao , Ren Tianheng
Published: April 2022

In this study, a novel T1RS.1BL translocation line RT843-5 was selected from a cross between wheat Mianyang11 (MY11) and Weining rye. The results of MC-FISH, PCR, and A-PAGE showed that RT843-5 contained two intact T1RS.1BL translocation chromosomes. RT843-5 showed resistance to the most virulent and frequently occurring stripe rust races/isolates. Additionally, RT843-5 showed resistance in the field in locations where stripe rust outbreaks have been the most severe in China. Genetic analysis indicated one new gene for stripe rust resistance, located on 1RS of RT843-5, which was tentatively named YrRt843. Furthermore, the chlorophyll content, the activities of catalase (CAT), and superoxide dismutase (SOD), and the net photosynthetic rate (Pn) of RT843-5 were significantly higher than those in its wheat parent MY11, whereas malondialdehyde (MDA) accumulation was significantly lower after anthesis in RT843-5 compared to in MY11. RT843-5 had a significantly higher 1000-kernel weight and yield than MY11. The results indicated that RT843-5 exhibited functional stay-green traits after anthesis, that delayed the senescence process in wheat leaves during the filling stage and had positive effects on grain yield. The present study indicated that Weining rye may carry untapped variations as a potential source of resistance, and that RT843-5 could be an important material for wheat breeding programs in the future.
Bioinformatics and Screening of a Circular RNA-microRNA-mRNA Regulatory Network Induced by Coxsackievirus Group B5 in Human Rhabdomyosarcoma Cells
Authors: Li Jing , Teng Peiying , Yang Fan , Ou Xia , Zhang Jihong , Chen Wei
Published: April 2022

Hand, foot and mouth disease (HFMD) caused by Coxsackievirus Group B5 (CVB5) is one of the most common herpetic diseases in human infants and children. The pathogenesis of CVB5 remains unknown. Circular RNAs (CircRNAs), as novel noncoding RNAs, have been shown to play a key role in many pathogenic processes in different species; however, their functions during the process of CVB5 infection remain unclear. In the present study, we investigated the expression profiles of circRNAs using RNA sequencing technology in CVB5-infected and mock-infected human rhabdomyosarcoma cells (CVB5 virus that had been isolated from clinical specimens). In addition, several differentially expressed circRNAs were validated by RT-qPCR. Moreover, the innate immune responses related to circRNA-miRNA-mRNA interaction networks were constructed and verified. A total of 5461 circRNAs were identified at different genomic locations in CVB5 infections and controls, of which 235 were differentially expressed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis demonstrated that the differentially expressed circRNAs were principally involved in specific signaling pathways related to ErbB, TNF, and innate immunity. We further predicted that novel_circ_0002006 might act as a molecular sponge for miR-152-3p through the IFN-I pathway to inhibit CVB5 replication, and that novel_circ_0001066 might act as a molecular sponge for miR-29b-3p via the NF-κB pathway and for the inhibition of CVB5 replication. These findings will help to elucidate the biological functions of circRNAs in the progression of CVB5-related HFMD and identify prospective biomarkers and therapeutic targets for this disease.
Profiling of Transcriptome-Wide N6-Methyladenosine (m6A) Modifications and Identifying m6A Associated Regulation in Sperm Tail Formation in Anopheles sinensis
Authors: Liu Congshan , Cao Jianping , Zhang Haobing , Wu Jiatong , Yin Jianhai
Published: April 2022

Recent discoveries of reversible N6-methyladenosine (m6A) methylation on messenger RNA (mRNA) and mapping of m6A methylomes in many species have revealed potential regulatory functions of this RNA modification by m6A players—writers, readers, and erasers. Here, we first profile transcriptome-wide m6A in female and male Anopheles sinensis and reveal that m6A is also a highly conserved modification of mRNA in mosquitoes. Distinct from mammals and yeast but similar to Arabidopsis thaliana, m6A in An. sinensis is enriched not only around the stop codon and within 3′-untranslated regions but also around the start codon and 5′-UTR. Gene ontology analysis indicates the unique distribution pattern of m6A in An. sinensis is associated with mosquito sex-specific pathways such as tRNA wobble uridine modification and phospholipid-binding in females, and peptidoglycan catabolic process, exosome and signal recognition particle, endoplasmic reticulum targeting, and RNA helicase activity in males. The positive correlation between m6A deposition and mRNA abundance indicates that m6A can play a role in regulating gene expression in mosquitoes. Furthermore, many spermatogenesis-associated genes, especially those related to mature sperm flagellum formation, are positively modulated by m6A methylation. A transcriptional regulatory network of m6A in An. sinensis is first profiled in the present study, especially in spermatogenesis, which may provide a new clue for the control of this disease-transmitting vector.
Molecular and Signaling Mechanisms for Docosahexaenoic Acid-Derived Neurodevelopment and Neuroprotection
Authors: Kim Hee-Yong , Huang Bill X. , Spector Arthur A.
Published: April 2022

The neurodevelopmental and neuroprotective actions of docosahexaenoic acid (DHA) are mediated by mechanisms involving membrane- and metabolite-related signal transduction. A key characteristic in the membrane-mediated action of DHA results from the stimulated synthesis of neuronal phosphatidylserine (PS). The resulting DHA-PS-rich membrane domains facilitate the translocation and activation of kinases such as Raf-1, protein kinase C (PKC), and Akt. The activation of these signaling pathways promotes neuronal development and survival. DHA is also metabolized in neural tissues to bioactive mediators. Neuroprotectin D1, a docosatriene synthesized by the lipoxygenase activity, has an anti-inflammatory property, and elovanoids formed from DHA elongation products exhibit antioxidant effects in the retina. Synaptamide, an endocannabinoid-like lipid mediator synthesized from DHA in the brain, promotes neurogenesis and synaptogenesis and exerts anti-inflammatory effects. It binds to the GAIN domain of the GPR110 (ADGRF1) receptor, triggers the cAMP/protein kinase A (PKA) signaling pathway, and activates the cAMP-response element binding protein (CREB). The DHA status in the brain influences not only the PS-dependent signal transduction but also the metabolite formation and expression of pre- and post-synaptic proteins that are downstream of the CREB and affect neurotransmission. The combined actions of these processes contribute to the neurodevelopmental and neuroprotective effects of DHA.
Adhesion Molecule Profile and the Effect of Anti-VLA-4 mAb Treatment in Experimental Autoimmune Encephalomyelitis, a Mouse Model of Multiple Sclerosis
Authors: Pyka-Fościak Grażyna , Lis Grzegorz J. , Litwin Jan A.
Published: April 2022

In the course of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), the infiltration of lymphocytes and other inflammatory cells across the blood–brain barrier is associated with interactions between adhesion molecules expressed by infiltrating cells and vascular endothelium. Monoclonal antibodies (mAb) against the α4 subunit of α4-β1 integrin (VLA-4) show beneficial effects in both MS and EAE. (1) Background: The aim of this study was to examine the expression of selected adhesion molecules: VLA-4, VCAM-1, LFA-1, ICAM-1 and PECAM-1 in the successive phases of EAE and the effect of anti-VLA-4 mAb treatment on that expression. (2) Methods: EAE was induced in C57BL/6 mice by immunization with MOG35–55 peptide. The animals were killed in three successive phases of the disease: onset (day 13), peak (day 18) and chronic (day 28). Frozen sections of the lumbar spinal cord were examined by quantitative immunofluorescence microscopy. The expression of the studied molecules was quantified as the percentage of the cross-sectioned spinal cord lesion area occupied by immunopositive structures. (3) Results: The expression of the studied molecules showed two temporal patterns: (1) an increase in the onset phase, a maximum in the peak phase and a decrease in the chronic phase, which corresponded to the temporal pattern of the clinical score, the number of lesions and the inflammation level (ICAM-1, LFA-1 and PECAM-1), and (2) an increase in the peak phase and no significant change or further increase in the chronic phase (VCAM-1, VLA-4). Among the molecules studied, ICAM-1 and LFA-1 exhibited the highest expression levels in the peak phase of EAE. Anti-VLA-4 mAb inhibited the expression of not only VLA-4 but also other adhesion molecules. (4) Conclusions: The interactions of adhesion molecules governing the migration of leukocytes across the blood–brain barrier change in the successive phases of EAE. The therapeutic mechanism of anti-VLA-4 mAb treatment seems to include a complex influence on a variety of adhesion molecules expressed by infiltrating cells and vascular endothelium.
Machine Learning Based on Diffusion Kurtosis Imaging Histogram Parameters for Glioma Grading
Authors: Jiang Liang , Zhou Leilei , Ai Zhongping , Xiao Chaoyong , Liu Wen , Geng Wen , Chen Huiyou , Xiong Zhenyu , Yin Xindao , Chen Yu-Chen
Published: April 2022

Glioma grading plays an important role in surgical resection. We investigated the ability of different feature reduction methods in support vector machine (SVM)-based diffusion kurtosis imaging (DKI) histogram parameters to distinguish glioma grades. A total of 161 glioma patients who underwent magnetic resonance imaging (MRI) from January 2017 to January 2020 were included retrospectively. The patients were divided into low-grade (n = 61) and high-grade (n = 100) groups. Parametric DKI maps were derived, and 45 features from the DKI maps were extracted semi-automatically for analysis. Three feature selection methods [principal component analysis (PCA), recursive feature elimination (RFE) and least absolute shrinkage and selection operator (LASSO)] were used to establish the glioma grading model with an SVM classifier. To evaluate the performance of SVM models, the receiver operating characteristic (ROC) curves of SVM models for distinguishing glioma grades were compared with those of conventional statistical methods. The conventional ROC analysis showed that mean diffusivity (MD) variance, MD skewness and mean kurtosis (MK) C50 could effectively distinguish glioma grades, particularly MD variance. The highest classification distinguishing AUC was found using LASSO at 0.904 ± 0.069. In comparison, classification AUC by PCA was 0.866 ± 0.061, and 0.899 ± 0.079 by RFE. The SVM-PCA model with the lowest AUC among the SVM models was significantly better than the conventional ROC analysis (z = 1.947, p = 0.013). These findings demonstrate the superiority of DKI histogram parameters by LASSO analysis and SVM for distinguishing glioma grades.
Intrauterine Thoracoamniotic Shunting of Fetal Hydrothorax with the Somatex Intrauterine Shunt: Intrauterine Course and Postnatal Outcome
Authors: Grandt Joleen , Gottschalk Ingo , Geipel Annegret , Gembruch Ulrich , Simonini Corinna , Weber Eva , Berg Christoph , Müller Andreas , Strizek Brigitte
Published: April 2022

(1) Background: Severe fetal hydrothorax can be treated by intrauterine thoracoamniotic shunting (TAS). The aim of this study was to assess perinatal outcome and complication rates of TAS with a novel Somatex intrauterine shunt. (2) Methods: This is a single-center retrospective study of all fetuses with hydrothorax treated with TAS using a Somatex shunt between 2014 and 2020. (3) Results: A total of 39 fetuses were included in the study. Mean gestational age at first intervention was 27.4 weeks (range 19–33). Of these, 51% (n = 20) of fetuses had fetal hydrops, which resolved in 65% (13/20) before delivery. The live birth rate was 97% (n = 38), and 74% (n = 29) survived the neonatal period. The rate of postnatal pulmonary complications was high, with 88% of neonates requiring any kind of ventilatory support. There were 23% (n = 9) genetic abnormalities (trisomy 21 and Noonan syndrome). (4) Conclusions: TAS with a Somatex shunt has a high technical success rate, leading to high neonatal survival rates. Pregnancy and neonatal outcome is comparable to TAS for fetal hydrothorax using different shunt types.
Fertility after Curative Therapy for Sickle Cell Disease: A Comprehensive Review to Guide Care
Authors: Nickel Robert Sheppard , Maher Jacqueline Y. , Hsieh Michael H. , Davis Meghan F. , Hsieh Matthew M. , Pecker Lydia H.
Published: April 2022

Curative therapy for sickle cell disease (SCD) currently requires gonadotoxic conditioning that can impair future fertility. Fertility outcomes after curative therapy are likely affected by pre-transplant ovarian reserve or semen analysis parameters that may already be abnormal from SCD-related damage or hydroxyurea treatment. Outcomes are also likely affected by the conditioning regimen. Conditioning with myeloablative busulfan and cyclophosphamide causes serious gonadotoxicity particularly among post-pubertal females. Reduced-intensity and non-myeloablative conditioning may be acutely less gonadotoxic, but more short and long-term fertility outcome data after these approaches is needed. Fertility preservation including oocyte/embryo, ovarian tissue, sperm, and experimental testicular tissue cryopreservation should be offered to patients with SCD pursing curative therapy. Regardless of HSCT outcome, longitudinal post-HSCT fertility care is required.
Electrochemical Advanced Oxidation of Lamotrigine at Ti/DSA (Ta2O5-Ir2O5) and Stainless Steel Anodes
Authors: Meena Vinod Kumar , Ghatak Himadri Roy
Published: April 2022

The study presents kinetics of degradation and mineralization of an anti-epileptic drug Lamotrigine (LAM) in the aqueous matrix by electrochemical advanced oxidation process (EAOP) on Ti/DSA (Ta2O5-Ir2O5) and Stainless Steel (SS) anodes using sodium sulphate as supporting electrolyte. On both the anodes, kinetic behaviour was pseudo-first-order for degradation as well as mineralization of LAM. On Ti/DSA anode, maximum LAM degradation of 75.42% was observed at an associated specific charge of 3.1 (Ah/litre) at a current density of 1.38 mA/cm2 and 100 ppm Na2SO4 concentration. Maximum mineralization attained was 44.83% at an associated specific charge of 3.1 (Ah/litre) at a current density of 1.38 mA/cm2 and 50 ppm concentration of Na2SO4 with energy consumption of 2942.71 kWh/kgTOC. Under identical conditions on SS anode, a maximum of 98.92% LAM degradation was marked after a specific charge (Q) of 3.1 (Ah/litre) at a current density of 1.38 mA/cm2 and 100 ppm concentration of Na2SO4. Maximum LAM mineralization on SS anode was 98.53%, marked at a specific charge of 3.1 (Ah/litre) at a current density of 1.38 mA/cm2 and 75 ppm concentration of Na2SO4, with energy consumption of 1312.17 kWh/kgTOC. Higher Mineralization Current Efficiency (MCE) values were attained for EAOP on SS anode for both degradation and mineralization due to occurrence of combined electro-oxidation and electro-coagulation process in comparison to EAOP on Ti/DSA anode due to occurrence of lone electro-oxidation process.
E-democracy: an urgent need or a tribute to fashion? Legal analysis
Authors: Pyroha Ihor , Tokarchuk Liudmyla , Perezhniak Boris , Nikitenko Liliia , Berch Veronika
Published: April 2022

The development of the information society and the strengthening of e-democracy have already become an important priority for many countries around the world at the present stage of development. The implementation of this priority implies open and transparent public administration, and thus the transformation of political institutions and processes and the introduction of new forms of government. It is meaningful to analyze the concept of “e-democracy” and to understand the importance of ensuring this in the mechanism for the democracy of each individual state. The object of research is the legal analysis of e-democracy in view of the legal realities of foreign countries. The aim of the article is a legal analysis of the concept of "electronic democracy", including problematic issues of implementation of this mechanism, in order to understand whether this mechanism is an urgent need, or is a tribute to fashion and trends in the world practice. During the study, the following methods were used: systemic, systemic-functional, comparative, sociological, analysis, synthesis, analogy, observation, classification, statistical analysis. The article analyzes the phenomenon of e-democracy, identifies the main approaches to understanding it. On the example of international experience the mechanisms of e-democracy and the peculiarities of e-government are identified. There are propositions to improve the domestic legal mechanism for e-government in the article.
Analisis Kepuasan Kerja di Puskesmas Sukamenanti Kabupaten Pasaman Barat Berdasarkan Pengaruh Lingkungan, Kompensasi Dan Budaya Kerja
Authors: Deliza Efi
Published: April 2022

This study aims to determine the effect of work environment, compensation, and work culture on employee performance through job satisfaction as an intervening variable at Sukamenanti Public Health Center, West Pasaman Regency. The method used is multiple linear regression analysis and path analysis. by distributing questionnaires to 63 respondents. The results obtained that the work environment has a positive and significant effect on job satisfaction of Sukamenanti Public Health Center employees, West Pasaman Regency. Compensation has a positive and significant effect on the job satisfaction of Sukamenanti Public Health Center employees, West Pasaman Regency. Work culture has a positive and significant effect on job satisfaction of Sukamenanti Public Health Center employees, West Pasaman Regency. The work environment has a negative and insignificant effect on employee performance at Sukamenanti Health Center employees, West Pasaman Regency. Compensation has a positive and insignificant effect on employee performance at Sukamenanti Public Health Center employees, West Pasaman Regency. Work culture has a positive and significant effect on employee performance at Sukamenanti Health Center employees, West Pasaman Regency. Job satisfaction has a positive and significant effect on employee performance at Sukamenanti Health Center employees, West Pasaman Regency. Job satisfaction mediates the effect of the work environment on employee performance because the value of the direct influence is greater than the indirect effect. Job satisfaction mediates the effect of compensation on employee performance because the value of the direct influence is greater than the indirect effect. Job satisfaction mediates the influence of work culture on employee performance because the value of direct influence is greater than indirect influence
Guía de práctica clínica para el diagnóstico y manejo inicial de artritis reumatoide en el Seguro Social del Perú (EsSalud)
Authors: Salinas Ariel , Huaringa-Marcelo Jorge , Alfaro-Lozano José , Becerra-Chauca Naysha , Nieto-Gutierrez Wendy , Garcia-Gomero David , De la Jara Jesús , Calderón-Gallegos Julia , Flores César , Taype-Rondan Alvaro , Timaná-Ruiz Raúl , Salvador-Salvador Stefany , Carrera-Acosta Lourdes , Gamboa-Cárdenas Rocío
Published: April 2022

Introducción: La Artritis Reumatoide (AR) tiene adversas consecuencias en la salud su diagnóstico temprano y manejo óptimo requiere recomendaciones basadas en evidencia de alta calidad adaptadas a cada sistema de salud. Objetivo: Proveer recomendaciones clínicas basadas en evidencia para el diagnóstico y manejo inicial de la AR. Material y Métodos: Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos. El GEG formuló 10 preguntas clínicas a ser respondidas por la presente GPC. Se realizaron búsquedas sistemáticas de la evidencia publicada en PubMed y CENTRAL entre diciembre 2017 a julio 2019 (revisiones sistemáticas y –cuando fue considerado pertinente– estudios primarios). Se seleccionó la evidencia de mayor calidad para responder cada una de las preguntas clínicas planteadas. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE) y en reuniones de trabajo periódicas, el GEG usó dicha metodología para revisar la evidencia y formular las recomendaciones, los puntos de buena práctica clínica y los flujogramas. Finalmente, la GPC fue aprobada con Resolución N° 132 – IETSI – ESSALUD – 2019. Resultados: La presente GPC abordó 10 preguntas clínicas, divididas en dos temas: diagnóstico y manejo. En base a dichas preguntas se formularon 16 recomendaciones (5 fuertes y 11 condicionales), 45 puntos de buena práctica clínica, y 3 flujogramas. Conclusión: El presente artículo resume la metodología y las conclusiones basadas en evidencias de la GPC para el diagnóstico y manejo inicial de la AR en EsSalud.
Exploring Learners' Study Orientation, Information Literacy, and Wellbeing: A comparative review of four validated questionnaires
Authors: Salman Hira , Powell Leigh , Zary Nabil
Published: April 2022

Academic performance is critical in determining not just the success or failure of any educational institution but also the socio-economic growth of a nation. Academic success can be predicted using components of lifelong learning, namely, self-regulation, conscientiousness, mindsets, and motivation for learning To assess the learner's capacity to continue learning throughout life, there are many instruments, this review article will compare the four validated instruments to measure the level of cognitive strategy use and the regulation of cognition with the help of LASSI, wellbeing, students' (motivational) thinking strategies and attributions, epistemologies, perception of the learning environment by MED-NORD, MSLQ's application of many cognitive and metacognitive methods, as well as student access to various resources and lastly students' knowledge of what it takes to become self-directed learners, the several strategies they should use to do so, the required learning activities they must actively engage in, and the specific attributes they possess to help them monitor their own learning activities and their own skills by SRSSDL.
Limitation of parasitic absorption in designs of three-state terahertz quantum cascade lasers with direct-phonon injection
Authors: Wang Li , Lin Tsung-Tse , Wang Ke , Hirayama Hideki
Published: April 2022

To maximize the population inversion in terahertz quantum cascade lasers for high-temperature operation, the scheme of electron injection following direct-phonon emission is more attractive than the common way via resonant tunneling. If this direct-phonon injection can be realized within a simple quantum structure (only three quantum states), much higher optical gain is expected even at room temperature. However, the attempts of this design in experiments are full of challenges. In this work, the non-equilibrium Green’s function method is introduced to draw a full picture of the quantum transport in this design. It demonstrates that the optical gain is strictly limited by a parasitic absorption from one specific high-lying state. Moreover, a strategy is proposed to avoid this limitation.
Investigation of OvHV-2 virus in small ruminants in Western Turkey
Authors: PEKMEZ Kemal , KAPLAN Murat , ÖZKAN Buket , KALAYCI Gülnur
Published: April 2022

Malignant catarrhal fever (MCF) is a fatal disease of ruminants and has a worldwide distribution. The MCF virus (MCFV) group has currently known to contain 10 members. Ovine gammaherpesvirus 2 (OvHV-2) is one of the members of MCFV group and has economically importance in cattle. Sheep is the reservoir host of OvHV-2 while domestic goat is naturally susceptible species, although infection is generally asymptomatic in goat. In this study, the presence of OvHV-2 was investigated in sheep and goats by hemi-nested PCR in Aegean Region of west Turkey. Total of 138 sheep and goat samples which consist of 73 whole blood, 39 internal organs and 26 aborted fetuses were investigated. Thirty-seven blood samples, four fetal samples, and seven internal organ samples were found to be OvHV-2 positive. While 45.1% of the total sheep samples were found to be positive, only one goat sample was found positive. Similarly, previous studies have showed that prevalence of OvHV-2 in goats lower than sheep.
In het belang van het kind: gezien vanuit het kind en gezien vanuit de overheid
Authors: Levering Bas
Published: April 2022

In hoeverre is opvoeding een zaak van de overheid? Als opgroeiende kinderen in hun ontwikkeling worden geschaad, dan kan de rechter ingrijpen door kinderen onder toezicht te stellen of ouders uit de ouderlijke macht te ontheffen of ontzetten. Maar volgens velen is de armslag van de overheid te beperkt. Naar aanleiding van de recente gezinsdramas gaan er stemmen op voor meer en eerder overheidsingrijpen. De wetgever stelt voor om de rechtsgrond voor overheidsingrijpen te verruimen, waardoor het mogelijk wordt om ook kinderen met lichtere problemen onder toezicht te stellen of hun ouders opvoedingsondersteuning op te leggen. Uiteraard in het belang van het kind, maar hoe ziet dat belang er eigenlijk uit? Volgens pedagoog Bas Levering is het belang van het kind gelegen in de pedagogische relatie met zijn of haar opvoeders. Hij laat zien dat deze relatie vanwege haar bijzondere aard gevrijwaard moet blijven van al te gemakkelijke inmenging van buitenaf. Om die reden pleit hij voor een terughoudende rol van de overheid. Ook rechtsfilosoof Andreas Kinneging vindt dat een overheid de opvoeding van ouders niet zomaar kan en mag overnemen. De hedendaagse opvoedingsproblemen wijt hij aan de teloorgang van traditionele gezinswaarden. De tijd is naar zijn idee rijp voor een pedagogisch beschavingsoffensief.
OF REQUEST
Authors: Pal Dibakar
Published: April 2022

If a poor person requests, it is not news. If a rich requests a poor it is definitely news. If a tyrant dictator requests a proletariat it is dangerous news. The request of both rich and ruler awake suspect and fear simultaneously.