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Genetic testing, including whole genome, whole exome, and other next‐generation sequencing technologies, has evolved vastly in the past decade. With this, the number of identified genes and genetic variants is constantly increasing. Although a variety of databases and online tools exist that summarize, categorize, and classify genes, a clear guideline of which information is needed when reporting a gene and what to do when identifying a new gene is lacking. This includes the correct nomenclature, descriptive information about genetic loci and genetic variation, aliases, and correlated phenotypes. This tutorial is meant to serve as an introduction to reporting genes in a paper and provides an overview of available databases and tools to obtain all necessary information on the genes of interest. [ABSTRACT FROM AUTHOR]

In a nuclear or radiological incident, first responders must quickly and accurately measure radiation exposure among civilians as medical countermeasures are radiation dose-dependent and time-sensitive. Although several approaches have been explored to measure absorbed radiation dose, there is an important need to develop point-of-care (POC) bioassay devices that can be used immediately to triage thousands of individuals potentially exposed to radiation. Here we present a proof-of-concept study showing the use of a paper-based vertical flow immunoassay (VFI) to detect radiation dosimetry genes. Using labeled primers during amplification and a multiplex membrane, our results showed that the nucleic acid VFI can simultaneously detect two biodosimetry genes, CDKN1A and DDB2, as well as one housekeeping gene MRPS5. The assay demonstrated good linearity and precision with an inter- and intra-assay coefficient of variance <20% and <10%, respectively. Moreover, the assay showed its ability to discriminate non-irradiated controls (0 Gy) from irradiated samples (1 + 2 Gy) with an overall sensitivity of 62.5% and specificity of 100% (AUC = 0.8672, 95% CI: 0.723–1.000; p = 0.004). Interestingly, the gene combination also showed a dose-dependent response for 0, 1, and 2 Gy, similar to data obtained by real-time PCR benchmark. These preliminary results suggest that a VFI platform can be used to detect simultaneously multiple genes that can be then quantified, thus offering a new approach for a POC biodosimetry assay that could be rapidly deployed on-site to test a large population and help triage and medical management after radiological event. [ABSTRACT FROM AUTHOR]

R.A. Fisher's 1922 paper On the dominance ratio has a strong claim to be the foundation paper for modern population genetics. It greatly influenced subsequent work by Haldane and Wright, and contributed 3 major innovations to the study of evolution at the genetic level. First, the introduction of a general model of selection at a single locus, which showed how variability could be maintained by heterozygote advantage. Second, the use of the branching process approach to show that a beneficial mutation has a substantial chance of loss from the population, even when the population size is extremely large. Third, the invention of the concept of a probability distribution of allele frequency, caused by random sampling of allele frequencies due to finite population size, and the first use of a diffusion equation to investigate the properties of such a distribution. Although Fisher was motivated by an inference that later turned out to lack strong empirical support (a substantial contribution of dominance to quantitative trait variability), and his use of a diffusion equation was marred by a technical mistake, the paper introduced concepts and methods that pervade much subsequent work in population genetics. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to elucidate the connection between osteoclastic forkhead transcription factor O1 (FoxO1) and periodontitis and explore the underlying mechanism by which FoxO1 knockdown regulates osteoclast formation. Materials and Methods: A conventional ligature‐induced periodontitis model was constructed to reveal the alterations in the proportion of osteoclastic FoxO1 in periodontitis via immunofluorescence staining. Additionally, RNA sequencing (RNA‐seq) was performed to explore the underlying mechanisms of FoxO1 knockdown‐mediated osteoclastogenesis, followed by western blotting, quantitative polymerase chain reaction, and enzyme‐linked immunosorbent assay. Results: FoxO1+ osteoclasts were enriched in the alveolar bone in experimental periodontitis. Moreover, FoxO1 knockdown led to impaired osteoclastogenesis with low expression of osteoclast differentiation‐related genes, accompanied by an insufficient osteoclast maturation phenotype. Mechanistically, RNA‐seq revealed that the nuclear factor kappa B (NF‐κB) and nucleotide‐binding oligomerization domain‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling pathways were inhibited in FoxO1‐knockdown osteoclasts. Consistent with this, MCC950, an effective inhibitor of the NLRP3 inflammasome, substantially attenuated osteoclast formation. Conclusions: FoxO1 knockdown contributed to the inhibition of osteoclastogenesis by effectively suppressing NF‐κB signaling and NLRP3 inflammasome activation. This prospective study reveals the role of FoxO1 in mediating osteoclastogenesis and provides a viable therapeutic target for periodontitis treatment. [ABSTRACT FROM AUTHOR]

Aims: This study was designed to analyse the prevalence of class 1 and class 2 integron integrase genes among antibiotic‐resistant coliform bacteria isolated from paper currency circulating in Pakistan. Methods and Results: A total of 500 individual currency notes were collected from different food vending sites at Lahore, Pakistan. Bacterial population were identified by biochemical and PCR techniques. Antimicrobial susceptibility testing was performed by disc diffusion assay. The highest bacterial population on currency was found from street vendors and butcher shops. Escherichia coli was found to be the most prevalent coliform bacteria followed by Klebsiella sp. and Enterobacter sp. PCR amplification of antimicrobial resistance gene showed the presence of ampC, blaTEM, blaNDM‐1, qnrA, tet(A) and tet(B) genes among coliform isolates. A total of 47 integron integrase bearing strains of coliform bacteria were analysed. Sequence analysis showed the presence of dfrA1‐aadA1, dfrA1, dfrA5, dfrA7, aadA1, aadA4 cassette arrays in class 1 integron and dfrA1‐sat2‐aadA1 in class 2 integrase genes. Conclusion: Circulating currency was heavily contaminated with antimicrobial‐resistant coliform bacteria bearing class 1 and class 2 integron integrase genes. Significance and Impact of the Study: This study describes a potential threat of severe bacterial infections due to improper hand hygiene and community sanitation when dealing with the currency notes. [ABSTRACT FROM AUTHOR]

Objectives: To study the possible roles of type-2C protein phosphatases (PP2Cs) which have been confirmed to play roles in the response to diverse abiotic stresses in paper mulberry, we launched a series of genomic and functional studies of BpPP2Cs. Results: Sixty-three PP2C proteins in paper mulberry (Broussonetia papyrifera) were classified into 13 clades. Four BpPP2Cs with kinase domains were verified to be highly conserved in organisms ranging from algae to dicots. Seven pairs of BpPP2C genes were found to be expanding, and 18 BpPP2C genes had orthologues in Arabidopsis. BpPP2Cs showed broad expression in different tissues; the expression levels of 18 BpPP2Cs were changed and the phosphorylation levels of seven BpPP2C proteins increased at low temperature. Cold-response elements were found in the promoter region of 31 BpPP2Cs. Finally, Bp01g0320 was found to act as a hub protein and Bp01g0512 and Bp09g1278 played key roles in the ABA-signaling pathway and MAPK cascades, respectively. Conclusion: These results suggest that the PP2C gene family of paper mulberry is evolutionarily conserved and participates the regulation of the response to cold stress, which will play a vital role in further research on phosphatases in paper mulberry. [ABSTRACT FROM AUTHOR]

Nowadays, great efforts are made in developing new technology for rapid detection of specific DNA sequences, for environmental monitoring, forensic analysis and rapid biomedical diagnosis applications. Microfluidic paper-based analytical devices are suitable platforms for the development of point of care devices, due to their simple fabrication protocols, ease of use and low cost. Herein, a methodology for in situ detection of single strand DNA by using a colorimetric assay based on the formation of a DNAzyme within a paper substrate was developed. A DNAzyme that could only be formed in the presence of a specific sequence of the Y human amelogenin gene was designed. The performance of the DNAzyme was followed colorimetrically first in solution and then in paper substrates. The reaction was found to be specific to the Y fragment selected as analyte. The DNAzyme reaction on paper enabled the unequivocal colorimetric identification of the Y single strand DNA fragment both qualitatively, with the naked eye (143 ng), and quantitatively by image analysis (45.7 ng). As a proof of concept, a microfluidic paper-based device, pre-loaded with all DNAzyme reagents, was characterized and implemented for the simultaneous detection of X and Y single strand DNA fragments. Image 1 • Optimized methodology for in situ DNA detection in a paper device format. • Detection based on a DNAzyme using Y human amelogenin fragment. • Presents a non-enzymatic, colorimetric and rapid way to detect DNA sequences. • Detection: quantitatively by calculating the grey intensity values. • Detection: qualitatively by the presence of a green color "coffee ring". [ABSTRACT FROM AUTHOR]

• The MoS 2 -AuNPs probe showed uniquely inherited structure and excellent electrochemical characteristic. • The carbon paper functionalized with MoS 2 -AuNPs demonstrated the outstanding detection performance of p53 gene. • The biosensor exhibits a relatively lower detection limit of 68 fM for p53 gene detection. • The planned biosensor could discriminate well between the mutated and wild type p53 gene extracted from tumor cells. p53 gene is one of the most important anticancer genes and has been recognized as a typical biomarker for the early diagnosis, classification, and prognosis evaluation of cancers. In this work, a novel biosensing strategy integrating MoS 2 -AuNPs modified carbon paper (CP) conductive substrate and enzyme signal amplification technique was developed for p53 gene detection. We constructed an immobilized DNA S1 probe and a biotinylated DNA S3 probe, which could induce the formation of an S1-p53-S3 DNA sandwich complex in the presence of target sequence p53. After conjugating avidin-HRP via biotin-avidin reaction, 3,3',5,5'-tetramethylbenzidine would be catalyzed for signal amplification in the presence of H 2 O 2 so that the induced electrochemical response would change with proportional to the abundance of p53 gene. The proposed biosensor exhibited two linearities in the range of 1.0 × 10−15 ∼ 1.0 × 10-12 M and 1.0 × 10-12 ∼ 1.0 × 10-6 M, and the limit of detection (LOD) was 68 fM. No significant interferences were observed during detecting real serum samples. Moreover, it is worth pointing out that the biosensor together with its disposable, low-cost, and stable features can discriminate well between the mutated and wild type p53 gene extracted from tumor cells (wtTP53 in MCF-7 and mutated in SK-BR-3), demonstrating a promising applicability for clinical test. [ABSTRACT FROM AUTHOR]

The WOX (WUSCHEL-related homeobox) is a plant-specific transcription factor involved in plant development and stress response. However, few studies have been reported on the WOX gene in woody plants. In this study, 10 BpWOX genes were isolated from paper mulberry by RACE-PCR and categorized into three clades through phylogenetic analysis, ancient, intermediate and WUS clade. Among them, five members had the transcriptional activity detected by yeast one-hybrid and seven were uniquely localized to the nucleus through green fluorescent protein (GFP) observation. The expression patterns of BpWOX genes in different tissues and under diverse treatments were quantified by the qRT-PCR method. Results showed that BpWUS was expressed in the apical bud, stem and root, BpWOX5 and BpWOX7 functioned only in the root tip, and three BpWOXs regulated leaf development redundantly. BpWOX9 and BpWOX10 were induced by indole-3-acetic acid (IAA) or jasmonic acid (JA), while BpWOX2 was repressed by five phytohormones. Interestingly, most BpWOX genes were responsive to the abiotic stress stimuli of drought, salt, cold, and cadmium (CdCl2). Together, our study revealed that BpWOXs were functionally divergent during paper mulberry development and environmental adaptation, which might be related to their evolutionary relationships. Our work will benefit the systematic understanding of the precise function of WOX in plant development and environmental stress responses. [ABSTRACT FROM AUTHOR]

The relationship between the abundance of three functional genes and their corresponding biochemical reaction rates was investigated in several activated sludge and mill effluent microbial communities. Gene probes were prepared for two key denitrification genes (nirS and nirK) and for one nitrogen-fixation gene (nifH) and were validated using a variety of strains of known nir and nif genotype. ATP-based measures of viable cell numbers were used to provide total population sizes. In certain microbial communities (activated sludge enrichment cultures and multiple samples taken from the same mill primary clarifier), a strong correlation was observed between gene abundance and biochemical activity rates. However, when comparing several different nonenriched activated sludge bioreactors and separate primary clarifier microbial communities, the ratio of specific gene abundance to biochemical activity rates varied widely. These results suggest that in cases where a microbial community is not fully induced for a given biochemical activity or when very different communities are compared, quantitative gene probing can give a better measure of a community's potential to carry out the encoded function than can the relevant biochemical assay. However, the gene quantitation method employed here probably underestimated the true number of probed genes present in the microbial communities due to nirS and nifH genes in the communities having reduced DNA sequence similarity with the probes used.Key words: denitrification, nitrogen fixation, quantitative hybridization, activated sludge, primary clarifier.Nous avons examiné les liens existant entre l'abondance de trois gènes fonctionnels et la vitesse des réactions biochimiques correspondantes dans plusieurs communautés microbiennes de boues activées et d'effluents de papetières. Des sondes génétiques furent conçues pour des gènes clés de la dénitrification (nirS et nirK) et pour un gène de la fixation de l'azote (nifH), et furent validées à l'aide d'une panoplie de souches aux génotypes nir et nif connus. Des mesures de nombres de cellules viables se basant sur l'ATP ont été utilisées afin de procurer une estimation des tailles totales des populations. Dans certaines communautés microbiennes (cultures d'enrichissement de boues activées et échantillons multiples recueillis à partir d'un même clarificateur primaire de papetière), une forte corrélation a été observée entre l'abondance des gènes et les taux d'activités métaboliques. Toutefois, le rapport de l'abondance génétique spécifique sur les taux d'activité métabolique ont varié largement lorsque nous avons comparé divers bioréacteurs de boues non enrichies, ainsi que des communautés microbiennes de clarificateurs primaires de papetière distincts. Ces résultats nous indiquent que dans les cas où une activité biochimique n'est pas complètement induite chez une communauté bactérienne ou lorsque des communautés très différentes sont comparées, le sondage génétique quantitatif est d'avantage apte à fournir une mesure du potentiel d'une communauté à accomplir la fonction codée, que l'analyse biochimique pertinente. Cependant, la méthode de quantification des gènes employée ici a probablement sous-estimé le nombre véritable de gènes sondés présents dans la communauté microbienne, puisque les gènes nirS et nifH dans les communautés microbiennes avaient une similitude de séquence inférieure par rapport aux sondes utilisées.Mots clés : dénitrification, fixation de l'azote, hybridation quantitative, boues activées, clarificateur primaire.[Traduit par la Rédaction] [ABSTRACT FROM AUTHOR]

Introduction: Down syndrome as a genetic disorder is a popular research topic in molecular studies. One way to study Down syndrome is via bioinformatics. Methods: In this study, a gene expression profile from a microarray study was selected for more investigation. Results: The study of Down syndrome patients shows specific genes with differential expression and network centrality properties. These genes are introduced as RHOA, FGF2, FYN, and CD44, and their level of expression is high in these patients. Conclusion: This study suggests that besides chromosomes 21, there are additional contributing chromosomes to the risk of Down syndrome development. Besides, these genes could be used for clinical studies after more analysis. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson Disease (PD), the second most common chronic neurodegenerative disorder, is characterized by tremor, bradykinesia, rigidity, and postural instability. SHANK3 (SH3 and multiple ankyrin repeat domain 3) belongs to the extremely conserved ProSAP/Shank family of synaptic scaffolding proteins. Meanwhile, rs9616915 is a non-synonymous SNP (T>C) located in the exon 6 of the SHANK3 gene, which induces substitution of isoleucine to threonine and affects the function of the resulted protein. The present study aimed to evaluate whether rs9616915 polymorphism of SHANK3 is involved in the susceptibility to PD. Methods: The study subjects were 100 patients diagnosed with PD and 100 control volunteers. The obtained samples were evaluated by the polymerase chain reaction-restriction fragment length polymorphism method. Results: A significant association was found in genotype distribution between cases and controls. Individuals with TC genotype had increased risk of PD (P=0.035, OR=1.98, 95% CI=1.04 - 3.74). No significant difference was found in allele distribution (P=0.7). Conclusion: The findings suggest that the SHANK3 rs9616915 polymorphism is associated with an increased risk of PD in the population. Further studies are needed to confirm the role of the SHANK3 gene in PD. [ABSTRACT FROM AUTHOR]

Recently, novel biomolecules separation and detection methods based on ion concentration polarization (ICP) phenomena have been extensively researched due to its high amplification ratio and high-speed accumulation. Despite of these bright advances, the fabrication of conventional ICP devices still have complicated and times-consuming tasks. As an alternative platform, a paper have been recently used for the identical ICP operations. In this work, we demonstrated the selective preconcentration of a muc1 gene fragment as human breast cancer marker and a lamp-2 gene fragment as the cause of Danon disease in paper-based ICP devices. As a result, these two DNA fragments were successfully concentrated up to ~60 fold at different location in a single paper-channel. The device would be a promising platform for point-of-care device due to an economic fabrication, the easy extraction of concentrated sample and an easy disposability. [ABSTRACT FROM AUTHOR]

Mouse A9 cells, deficient in hypoxanthine phosphoribosyltransferase (EC 2.4.2.8), were fused with normal chick erythrocytes and selected in hypoxanthine-aminopterin-thymidine medium for cells with hypoxanthine phosphoribosyltransferase activity. Recovered hybrid cells produced the chick hypoxanthine phosphoribosyltransferase exclusively, as demonstrated by electrophoretic mobility and immunoprecipitation tests, even though no chick chromosomes or chick cell-surface antigens could be identified in the hybrids. Surprisingly, the expression of the chick hypoxanthine phosphoribosyl-transferase activity in the mouse/chick hybrids required the presence of aminopterin in the growth medium; in its absence, enzyme synthesis decreased markedly. Because of the rapid and reversible modulation of hypoxanthine phosphoribosyltransferase activity, the hybrid cells could proliferate equally well in media containing hypoxanthine-aminopterin-thymidine or 8-azaguanine. Cellular selection was definitely ruled out as a possible cause. These results confirm previous reports that specific genetic information can be selectively transferred from one cell to another of a distant species. Furthermore, they demonstrate that an avian gene, whose activity is normally expressed constitutively, can become facultative when integrated into a mammalian cell. This seems to be the first instance where heterologous gene activity has been shown to be reversibly modulated in hybrid cells.

Rearrangement and in most cases expression of the T cell rearranging genes gamma (TRG gamma) and T cell antigen receptor beta chain (TCR beta) genes were studied in 19 cases of T cell acute malignancies where the surface phenotype is representative of the different stages of thymic maturation. TCR alpha gene transcription was also studied. TRG gamma and TCR beta genes were found to be rearranged in all but one case. The TRG gamma rearrangement pattern seen in most cases is compatible with biallelic rearrangement by loop excision involving the J gamma 2 regions. The sizes of all but two rearranged bands were identical to those of the rearranged bands seen in polyclonal T lymphocytes also studied in this work. One identical-sized band was found in 11 of the 18 rearranged cases. The expression of TRG gamma mRNA (transcripts of 1.6 kilobases [kb]) was highly variable from case to case and did not correlate with the stage of differentiation of the malignant cells, the expression of the molecules CD4 and CD8, the expression and size of the transcripts of the TCR beta genes, and the transcription of TCR alpha genes. In one CD3 + case, strong expression of the TRG gamma transcripts coexisted with the exclusive presence of TCR beta mRNA of 1.0 kb. The cells from this case did not react with anti-Ti antibody and exhibited no natural killer activity. These findings are suggestive of a malignancy that may express the recently isolated CD3-TRG gamma complex.

Histidine auxotrophs of Micrococcus luteus strain ATCC 27141 were induced by treatment of the parent strain with N-methyl-N'-nitro-N-nitrosoguanidine. Auxotrophs were biochemically characterized by examining culture accumulations of histidine intermediates, using paper chromatography and the Bratton-Marshall test, and growth responses to L-histidinol. his(IG) mutants failed to accumulate Pauly-positive imidazoles; his(EAHF) mutants accumulated 5-amino-1-ribosyn-4-imidazole carboxamide; hisB mutants accumulated imidazoleglycerol; hisC mutants accumulated imidazoleacetol; hisD mutants, but did stimulate all other histidine mutants, blocked at earlier steps in the biosynthetic pathway. In addition, imidazoleglycerol phosphate dehydrase activity was assayed in representative mutants of each class. hisB mutants lacked activity for this enzyme.--Two -point, three-point, and cotransformation analyses resolved linkage relationships of histidine genes and in two gene clusters aided in determining their sequences. Histidine biosynthetic genes exist in at least four separate, unlinked regions of the chromosome. One histidine gene cluster linked to a tryptophan gene cluster and appears to be contiguous in the sequence his(IG) -his(EAHF)-trpE-trpC-trpA. A second and unlinked histidine cluster has the tentative gene sequence his(EAHF)-hisB-hisC-his(EAHF). The hisD gene and an unclassified mutant site his-94 are not linked to any of the other histidine genes examined in this study or to each other.