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In this paper, we prove that the classifying functors W ¯ and Diag ° N are simplicially homotopy equivalent. Using this equivalency, we define classifying simplicial modules and give an alternative definition of (co)homology of crossed modules of algebras. [ABSTRACT FROM AUTHOR]

Dual-specificity thyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a strong therapeutic target to ameliorate cognitive functions of Down Syndrome (DS). Genetic normalization of Dyrk1a is sufficient to normalize early cortical developmental phenotypes in DS mouse models. Gyrencephalic human neocortical development is more complex than that in lissencephalic mice; hence, cerebral organoids (COs) can be used to model early neurodevelopmental defects of DS. Single copy DYRK1A knockout COs (sc DYRK1AKO-COs) can be generated from manipulated DS derived (DS-) induced pluripotent stem cells (iPSCs) and genetic normalization of DYRK1A is expected to result in corrected neurodevelopmental phenotypes that can be reminiscent of normal COs. DYRK1A knock-in ( DYRK1AKI) COs can be derived after genetic manipulations of normal iPSCs and would be valuable to evaluate impaired neocortical development as can be seen in DS-COs. DYRK1A mutations cause severe human primary microcephaly; hence, dose optimization studies of DYRK1A inhibitors will be critical for prenatal therapeutic applications in DS. Several doses of DYRK1A inhibitors can be tested in the neurodevelopment process of DS-COs and DS-sc DYRK1AKO-COs would be used as optimum models for evaluating phenotypic ameliorations. Overdose drug exposure in DS-COs can be explained by similar defects present in DS-ba DYRK1AKO-COs and DYRK1AKO-COs. There are several limitations in the current CO technology, which can be reduced by the generation of vascularized brain-like organoids giving opportunities to mimic late-stage corticogenesis and complete hippocampal development. In the future, improved DS- DYRK1AKO-COs can be efficient in studies that aim to generate efficiently transplantable and implantable neurons for tissue regeneration alternatives in DS individuals. [ABSTRACT FROM AUTHOR]

Background: Even though complement 1q nephropathy (C1qN) was first introduced in 1985, this entity is still unknown and recognized by clinicians due to its rare prevalence (0.2 - 2.5 %) and insufficient emphasis. Description of the case: A 50-year-old woman was incidentally found to have non-nephrotic proteinuria with a normal glomerular filtration rate. Renal biopsy revealed C1qN with severe fibrosis. The presence of consanguinity and kidney diseases in family members of the patient led to genetic research, and homogenous mutation of c.991G>T (p.G331C) in the WD-repeat domain 19 (WDR19) gene was found. The same homozygous and heterozygous mutations in the WDR gene were found in the relatives of our patient with kidney diseases. One year of follow-up with methylprednisolone and mycophenolate mofetil treatment resulted in partial remission of the kidney disease. Conclusion: Renal biopsy for patients with non-nephrotic proteinuria without delay is suggested as it might be a surrogate marker of severe injury. Genetic mutations in the WDR19 gene should be searched for C1qN pathogenesis. This is the first adult case report on C1qN from Turkey. [ABSTRACT FROM AUTHOR]

Background: The mitochondrial carrier homolog 2 (MTCH2) is a mitochondrial outer membrane protein regulating mitochondrial metabolism and functions in lipid homeostasis and apoptosis. Experimental data on the interaction of MTCH2 with viral proteins in virus-infected cells are very limited. Here, the interaction of MTCH2 with PA subunit of influenza A virus RdRp and its effects on viral replication was investigated., Methods: The human MTCH2 protein was identified as the influenza A virus PA-related cellular factor with the Y2H assay. The interaction between GST.MTCH2 and PA protein co-expressed in transfected HEK293 cells was evaluated by GST-pull down. The effect of MTCH2 on virus replication was determined by quantification of viral transcript and/or viral proteins in the cells transfected with MTCH2-encoding plasmid or MTCH2-siRNA. An interaction model of MTCH2 and PA was predicted with protein modeling/docking algorithms., Results: It was observed that PA and GST.MTCH2 proteins expressed in HEK293 cells were co-precipitated by glutathione-agarose beads. The influenza A virus replication was stimulated in HeLa cells whose MTCH2 expression was suppressed with specific siRNA, whereas the increase of MTCH2 in transiently transfected HEK293 cells inhibited viral RdRp activity. The results of a Y2H assay and protein-protein docking analysis suggested that the amino terminal part of the viral PA (nPA) can bind to the cytoplasmic domain comprising amino acid residues 253 to 282 of the MTCH2., Conclusion: It is suggested that the host mitochondrial MTCH2 protein is probably involved in the interaction with the viral polymerase protein PA to cause negative regulatory effect on influenza A virus replication in infected cells., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The human C14orf166 protein, also known as RNA transcription, translation, and transport factor, shows positive modulatory activity on the cellular RNA polymerase II enzyme. This protein is a component of the tRNA-splicing ligase complex and is involved in RNA metabolism. It also functions in the nucleo-cytoplasmic transport of RNA molecules. The C14orf166 protein has been reported to be associated with some types of cancer. It has been shown that the C14orf166 protein binds to the influenza A virus RNA polymerase PA subunit and has a stimulating effect on viral replication. In this study, candidate interactor proteins for influenza A virus PA protein were screened with a Y2H assay using HEK293 Matchmaker cDNA. The C14orf166 protein fragments in different sizes were found to interact with the PA. The three-dimensional structures of the viral PA and C14orf166 proteins interacting with the PA were generated using the I-TASSER algorithm. The interaction models between these proteins were predicted with the ClusPro protein docking algorithm and analyzed with PyMol software. The results revealed that the carboxy-terminal end of the C14orf166 protein is involved in this interaction, and it is highly possible that it binds to the carboxy-terminal of the PA protein. Although amino acid residues in the interaction area of the PA protein with the C14orf166 showed distribution from 450th to 700th position, the intense interaction region was revealed to be at amino acid positions 610-630., (© 2023 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.)

Background: Despite low virulence of Stenotrophomonas maltophilia, it represents one of the leading drug-resistant bacteria. We report a large outbreak of S. maltophilia infection associated with an unexpected source, which turned out to be a commercial needleless blood gas injector., Methods: Over a period from January 1 to December10, 2021, 113 patients were identified to have S. maltophilia infection as documented by positive cultures from the clinical samples, extracorporeal membrane oxygenation (ECMO) water heater devices and commercial needleless blood gas injectors., Results: Sixty-seven isolates (59 clinical, 4 ECMO, 4 blood gas injectors) were sent for molecular analysis. Both arbitrarily primed polymerase chain reaction and pulsed-field gel electrophoresis analyses showed 12 distinct genotypes. Of 67 isolates, 58 were clonally related (86.6%), with 52 indistinguishable strains from 4 blood gas needleless injectors, 46 patients' samples (78%), and 2 ECMO samples (50%). Two ECMO samples and 1 clinical sample were clonally identical., Conclusions: In the event that eradication of infections would not be possible despite taking all environmental disinfection measures including the ECMO devices, unexpected sources, such as a commercial needleless blood gas injector, should not be omitted from the list for surveillance. In addition, obtaining surveillance cultures of ECMO water reservoirs should be placed in the routine clinical practice., (Copyright © 2022 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: Interferons (IFNs) are one of the most important components of innate immunity against viruses, especially those carrying the RNA genomes such as influenza viruses. Upon viral infection, the IFNs are rapidly secreted, inducing the expression of several genes in the target cells and establishing an antiviral state. In this study, the effects of proteins encoded by some IFN-related genes on influenza A virus RNA-dependent RNA polymerase enzyme were investigated. We evaluated the importance of these proteins in the pathogenesis of different influenza A virus types., Materials and Methods: The IFN-related genes were amplified by polymerase chain reaction from the HEK293 cDNA library and cloned into pCHA expression vector. The expression of genes and subcellular localizations of the proteins were determined by Western blotting and immunofluorescence staining, respectively. The effects of IFNs-related proteins on virus RdRP enzyme were determined by influenza A virus mini-replicons., Results: The study revealed that the influenza A virus infections significantly altered the transcript level of the IFN-related CCL5, IFIT1, IFIT3, IFITM3 , and OAS1 genes in HEK293 cells. It was determined that the alteration of the gene expression was also related to the virus type. The mini-replicon assays showed that the transient expression of CCL5, IFI27, OAS1, IFITM3, IFIT1 , and IFIT3 have inhibitory effects on WSN and/or DkPen type virus RdRP enzymes. We observed that the proteins except OAS1 inhibited WSN type RdRP enzyme at a higher level than that of DkPen enzyme., Conclusion: It was concluded that influenza A virus infection significantly alters the IFN-related gene expression in the cells. Most of the proteins encoded from these genes showed an inhibitory effect on the virus RdRP enzymes in the HEK293 cells. The inhibition of the influenza virus RdRP with IFN-related proteins may be the result of direct or indirect interactions between the host proteins and the viral enzyme subunits., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Turk J Pharm Sci, Published by Galenos Publishing House.)

Background: Replication of the influenza A viruses occurs in the cells through the viral RdRP consisting of PB1, PB2, and PA. Several cellular proteins are involved in these processes. This study aims to reveal the interaction between human SNX2 protein and the PA protein and the effects of the SNX2 on the virus replication., Results: To identify potential host interacting proteins to the PA, yeast two-hybrid assay was carried out with HEK293 cell cDNA library and the PA as a bait. We focused on SNX2 protein, which interacts with the PA in the yeast cells. By using the co-immunoprecipitation assays, it has been demonstrated that the amino-terminal part of the PA was important for binding to the SNX2. Immunolocalization of the proteins in HeLa cells supported this interaction. Knockdown of the SNX2 with siRNA in the cells resulted in a significant increase in both viral transcripts and virus growth. However, the increase of SNX2 in transfected cells didn't cause a significant change in the viral RdRP activity in minireplicon assay. This may suggest that the negative effect of SNX2 on the virus replication could be saturated with its authentic intra-cellular amount., Conclusions: This study revealed that the SNX2 and PA protein interact with each other in both yeast and HEK293 cells, and the SNX2 has a negative regulatory function on the virus replication. However, more knowledge is required to elucidate the action mechanism of the SNX2 on the influenza A virus replication at the molecular level., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Statement of Problem: The preparation design and fabrication materials directly affect the clinical success of endocrown restorations, and yet, knowledge is lacking about the biomechanical impact of specific designs or materials on endocrown restorations., Purpose: The purpose of this in vitro and finite element analysis study was to evaluate the biomechanical behavior of endocrown restorations., Material and Methods: A total of 36 freshly extracted mandibular first molars were collected. The teeth were prepared as per 2 different preparation geometries: with the buccal wall intact (Class 2) and without the buccal wall (Class 3). Teeth were restored with endocrowns made from 3 different fabricating materials, Vita Enamic, GC Cerasmart, and Lava Ultimate. To analyze the in vitro fracture strength, cemented endocrowns were loaded in a universal test machine with a 200-N oblique force until the restoration fractured. Finite element analysis was used to evaluate the stress distribution on both the dentin tissue and the restorative materials. The data were analyzed with a 2-way ANOVA test and the Tukey post hoc test (α=.05)., Results: No significant differences were found between the different preparation designs (Class 2 and Class 3) on fracture strength (P>.05). The highest mean ±standard deviation fracture strength values were found in the Lava Ultimate material (Class 2, 606.20 ±293; Class 3, 659.40 ±226 N) (P>.05), but the lowest fracture strength test values were obtained in the Vita Enamic material (Class 2, 439.60 ±136; Class 3, 340 ±98 N) (P>.05) for both preparation design test groups., Conclusions: A statistically significant difference was not found between the 2 tooth preparation classifications. However, significant differences were observed among the test groups in the Class 2 preparation specimens. The Class 2 preparation design exhibited a higher number of irreparable failures., (Copyright © 2021 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Influenza A viruses frequently change their genetic characteristics, which leads to the emergence of new viruses. Consequently, elucidation of the relationship between influenza A virus and host cells has a great importance to cope with viral infections. In this study, it was aimed to determine expression profiles of interferon response genes in human embryonic kidney 293 (HEK293) cells infected with human (A/WSN-H1N1) and avian influenza A viruses (duck/Pennsylvania/10218/84/H5N2) or transfected with plasmids encoding viral RdRP subunits and, to obtain clues about the genes that may be important for the viral pathogenesis. The HEK293 cells cultured in a 12-well plate were infected with influenza A viruses or transfected with plasmids encoding viral polymerase. Total RNA extraction and cDNA preparation were carried out with commercial kits. Qiagen 96-well-RT 2 Profiler PCR Array plates designated for interferons response genes were used for quantitation of the transcripts. The relative quantities of transcripts were normalized with STAT3 gen, and the results were evaluated. Quantitative RT-PCR results showed that there are substantial differences of the interferon response gene transcription in cells infected with viruses or transfected with plasmids. A higher number of interferon-related genes were found to be downregulated in the cells infected with DkPen compared to WSN. On the other hand, significant differences in the expression profiles of interferon response genes were observed in the cells expressing viral PA protein. In particular, avian influenza PA protein was found to cause more aggressive changes on the transcript levels. Human and avian influenza A viruses cause a substantial change in interferon response gene expression in HEK293 cells. However, a higher number of genes were downregulated in the cells infected with avian influenza DkPen compared to WSN. It has been also concluded that the viral PA protein is one of the important viral factors affecting the transcript level of host genes., Competing Interests: CONFLICT OF INTEREST: none declared, (Copyright © 2021 The Author(s).)

Objective: To determine the role of vascular endothelial growth factor (VEGF) in placental hypoperfusion in obesity., Methods: The prospective study enrolled women with a first-trimester singleton pregnancy in Izmir, Turkey, between January and April 2011. Participants were divided into three groups: obese (body mass index [BMI, calculated as weight in kilograms divided by the square of height in meters] >30) with cesarean delivery; normal weight (BMI <30) with vaginal delivery (NVD); and healthy controls (BMI <30) with cesarean delivery. Before delivery, serum C-reactive protein (CRP), and uterine and fetal Doppler measurements were taken. VEGF was evaluated immunohistochemically from the umbilical cord., Results: Overall, 109 women completed the study: obesity group (n=13, 11.9%), NVD group (n=50, 45.9%), and control group (n=46, 42.2%). Serum CRP was higher in the obesity group than in the control or NVD groups (P=0.009). VEGF score was highest in the NVD group (9.39 ± 3.11), and lowest in the obesity group (4.58 ± 2.78) (P<0.001). VEGF score decreased by 0.81 for each increase in BMI of 1 (P=0.002)., Conclusions: Maternal obesity was related to decreased VEGF expression. Although not supported by Doppler findings, decreased VEGF expression owing to maternal obesity might trigger endothelial dysfunction and inflammation., (© 2020 International Federation of Gynecology and Obstetrics.)

Objective: This study evaluates cardiovascular disease (CVD) risk among women undergoing natural menopause or surgically induced menopause through the measurement of serum growth differentiation factor-15 (GDF-15), B-type natriuretic peptide (BNP), ischemia modified albumin (IMA), total cholesterol, LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglyceride, fibrinogen, and C-reactive protein (CRP)., Materials and Methods: The study included women with surgically induced menopause (n = 50) and women undergoing natural menopause (n = 50). The two study groups were matched according to age, body mass index, menopause duration. GDF-15, BNP, IMA, total cholesterol, LDL-C, HDL-C, triglyceride, fibrinogen, and CRP were measured., Results: There was no significant difference in GDF-15, BNP, IMA, total cholesterol, LDL-C, HDL-C, triglyceride, fibrinogen, and CRP results between the two groups., Conclusion: We conclude that there is no increase in CVD risk among women aged 40-50 with surgically induced menopause relative to matched control subjects undergoing normal age-related menopause.