Molecular Epidemiology of blaCMY-1, blaCMY-2, blaFOX Genes in K. pneumoniae From Elderly Patients in Tehran, Iran

The growth rate of the population aging is increasing worldwide. To assess antimicrobial susceptibility of extended-spectrum β-lactamase- (ESBL-) producing Klebsiella pneumoniae Isolated from Patients aging in Rasool Akram, Hospital, as well as to identify AmpC genes. 100 K. pneumoniae strain isolated from different clinical samples. Isolates resistant to oxyimino-cephalosporins and to cefoxitin evaluated to phenotypic ESBL production and to phenotypic AmpC production, respectively. Detection of resistance genes was then performed using primers specific for AmpC genes. Piperacillin/tazobactam and carbapenems remained the active β-lactam antibiotic against K. pneumoniae. ESBLs were detected among 40 (40%) of K. pneumoniae isolates. CMY-1 gene was detected in 34.3% of all AmpC-positive isolates, whereas CMY-2 and FOX genes were 14.2% and 28.6%, respectively. The consumption of Carbapenem family drugs is high in Iranian hospitals which are used as a first line of treatment without antibiotic susceptibility testing. Therefore, increase in antibiotic resistance to this family drugs is unavoidable in the near future. Therefore, it is necessary to take the necessary measures to modify the administration and use of antibiotics.

Cystic hygroma and esophageal atresia with tracheoesophageal fistula: Is there a genetic association?

Background: Tracheoesophageal fistula (TEF) is associated with many other congenital anomalies like cardiac, renal, and vertebral, but the association with cystic hygroma is very rare. Case Presentation: We report a neonate, antenatally diagnosed with cystic hygroma of the neck and incidentally diagnosed to have TEF. The baby was operated on after adequate stabilization and the cystic hygroma was managed with injection sclerotherapy. The genetic analysis for the FOX genes complex has been done in this case and the results showed no association between the two. Conclusion: There is a need for future studies to find out if the association between cystic hygroma and TEF is by chance or if any embryological or genetic cause can be attributed to it.

The Genetic Network of Forkhead Gene Family in Development of Brown Planthoppers

We identified 18 distinct Fox genes in the genome of the brown planthopper, Nilaparvata lugens, and further found a novel insect-specific subfamily that we temporarily named FoxT. A total of 16 genes were highly expressed in the eggs, while NlFoxL2 and NlFoxT are female- and male-specific genes, respectively. Large scale RNAi and RNA-seq analyses were used to reveal the functions and potential targets of NlFoxs. In the eggs, NlFoxA, NlFoxN1 and NlFoxN2 are indispensable to early embryogenesis by regulating different target genes; NlFoxG and NlFoxQ co-regulate NlSix3 for brain development; and NlFoxC, NlFoxJ1 and NlFoxP have complementary effects on late embryogenesis. Moreover, NlFoxA, NlFoxNl and NlFoxQ have pleiotropism. NlFoxA and NlFoxQ regulate the expression of NlCHS1 and cuticular proteins, respectively, thereby participating in the formation of cuticles. NlFoxN1, which regulates the expression of NlKrt9 is involved in the formation of intermediate filament frameworks. Our previous studies have revealed that NlFoxL2 and NlFoxO play important roles in chorion formation and wing polyphenism. Altogether, N. lugens Fox genes exhibit functional diversity in embryonic development and organogenesis. This comprehensive study combines genomics, transcriptomics and phenomics, thereby constructing a complex genetic network that spans the entire life cycle of the brown planthopper.

Whole exome sequencing identifies FOXL2, FOXA2 and FOXA3 as candidate genes for monogenic congenital anomalies of the kidneys and urinary tract

Background Congenital anomalies of the kidneys and urinary tract (CAKUT) constitute the most common cause of chronic kidney disease in the first three decades of life. Variants in four Forkhead box (FOX) transcription factors have been associated with CAKUT. We hypothesized that other FOX genes, if highly expressed in developing kidney, may also represent monogenic causes of CAKUT. Methods We here performed whole exome sequencing (WES) in 541 families with CAKUT and generated 4 lists of CAKUT candidate genes: A) 36 FOX genes showing high expression during renal development, B) 4 FOX genes known to cause CAKUT to validate list A; C) 80 genes that we identified as unique potential novel CAKUT candidate genes when performing WES in 541 CAKUT families, and D) 175 genes identified from WES as multiple potential novel CAKUT candidate genes. Results To prioritize potential novel CAKUT candidates in FOX gene family, we overlapped 36 FOX genes (list A) with list C and D of WES-derived CAKUT candidates. Intersection with list C, identified a de novo FOXL2 in-frame deletion in a patient with eyelid abnormalities and ureteropelvic junction obstruction, and a homozygous FOXA2 missense variant in a patient with horseshoe kidney. Intersection with list D, identified a heterozygous FOXA3 missense variant in a CAKUT family with multiple affected individuals. Conclusion We hereby identified FOXL2, FOXA2 and FOXA3 as novel monogenic candidate genes of CAKUT, supporting the utility of a paralog-based approach to discover mutated genes associated with human disease.

Analysis of Fox genes in Schmidtea mediterranea reveals new families and a conserved role of Smed-foxO in controlling cell death

The forkhead box (Fox) genes encode transcription factors that control several key aspects of development. Present in the ancestor of all eukaryotes, Fox genes underwent several duplications followed by loss and diversification events that gave rise to the current 25 families. However, few Fox members have been identified from the Lophotrochozoa clade, and specifically from planarians, which are a unique model for understanding development, due to the striking plasticity of the adult. The aim of this study was to identify and perform evolutionary and functional studies of the Fox genes of lophotrochozoan species and, specifically, of the planarian Schmidtea mediterranea. Generating a pipeline for identifying Forkhead domains and using phylogenetics allowed us the phylogenetic reconstruction of Fox genes. We corrected the annotation for misannotated genes and uncovered a new family, the QD, present in all metazoans. According to the new phylogeny, the 27 Fox genes found in Schmidtea mediterranea were classified into 12 families. In Platyhelminthes, family losses were accompanied by extensive gene diversification and the appearance of specific families, the A(P) and N(P). Among the newly identified planarian Fox genes, we found a single copy of foxO, which shows an evolutionary conserved role in controlling cell death.

Analysis of Fox genes in Schmidtea mediterranea reveals new families and a conserved role of Smed-foxO in controlling cell death

The forkhead box (Fox) genes encode transcription factors that control several key aspects of development. Present in the ancestor of all eukaryotes, Fox genes underwent several duplications followed by loss and diversification events that gave rise to the current 25 families. However, few Fox members have been identified from the Lophotrochozoa clade, and specifically from planarians, which are a unique model for understanding development, due to the striking plasticity of the adult. The aim of this study was to identify and perform evolutionary and functional studies of the Fox genes of lophotrochozoan species and, specifically, of the planarian Schmidtea mediterranea. Generating a pipeline for identifying Forkhead domains and using phylogenetics allowed us the phylogenetic reconstruction of Fox genes. We corrected the annotation for misannotated genes and uncover a new family, the QD, present in all metazoans. According to the new phylogeny, the 27 Fox genes found in Schmidtea mediterranea were classified into 12 families. In Platyhelminthes, family losses were accompanied by extensive gene diversification and the appearance of specific families, the A(P) and N(P). Among the newly identified planarian Fox genes, we found a single copy of foxO, which shows an evolutionary conserved role in controlling cell death.Author summaryTranscription factors are the key elements that regulate gene expression in the nucleus. The forkhead box (Fox) transcription factors are one of the most numerous and they control key aspects of development. Fox genes were already present in the ancestor of all eukaryotes, and then underwent several duplications followed by loss and diversification events that gave rise to the current Fox families in the different species. The available data classifies Fox genes in 25 families, but they include few members corresponding to Lophotrocozoa, one of the two invertebrate phyla that includes annelids, molluscs or platyhelmintes. In this study we identify and perform evolutionary studies of the Fox genes of several lophotrochozoan species and, specifically, of the planarian Schmidtea mediterranea. The result is the correction of the annotation of Fox genes from many species, proposing a new nomenclature, and the identification of new families; the QD family, present in all metazoans, and the A(P) and N(P) families, specific of Platyhelminthes. We also study the function of Schmidtea mediterranea foxO, a gene involved in aging and cancer in other species, showing its evolutionary conserved role in controlling cell death according to cell metabolism.

FoxB, a new and highly conserved key factor in arthropod dorsal–ventral (DV) limb patterning

Forkhead box (Fox) transcription factors evolved early in animal evolution and represent important components of conserved gene regulatory networks (GRNs) during animal development. Most of the researches concerning Fox genes, however, are on vertebrates and only a relatively low number of studies investigate Fox gene function in invertebrates. In addition to this shortcoming, the focus of attention is often restricted to a few well-characterized Fox genes such as FoxA (forkhead), FoxC (crocodile) and FoxQ2. Although arthropods represent the largest and most diverse animal group, most other Fox genes have not been investigated in detail, not even in the arthropod model species Drosophila melanogaster. In a general gene expression pattern screen for panarthropod Fox genes including the red flour beetle Tribolium castaneum, the pill millipede Glomeris marginata, the common house spider Parasteatoda tepidariorum, and the velvet worm Euperipatoides kanangrensis, we identified a Fox gene with a highly conserved expression pattern along the ventral ectoderm of arthropod and onychophoran limbs. Functional investigation of FoxB in Parasteatoda reveals a hitherto unrecognized important function of FoxB upstream of wingless (wg) and decapentaplegic (dpp) in the GRN orchestrating dorsal–ventral limb patterning.

Identification and expression of forkhead box genes in the Chinese giant salamander Andrias davidianus

In the present study, 21 forkhead box (Fox) genes were identified in Andrias davidianus, including 13 full-length genes and eight partial sequences. Phylogenetic analysis showed that most were conserved in other investigated amphibians, whereas the Foxk1 gene was found exclusively in A. davidianus. Molecular evolution analysis indicated that most Fox genes underwent purifying selection, whereas two sites of the adFoxp4 gene showed positive selection and were located on the adFoxp4 protein surface. Expression profiles of all Fox genes identified were analysed in the hypothalamic–pituitary–gonad axis by reverse transcription–quantitative polymerase chain reaction. Eighteen genes exhibited sexually dimorphic expression (15 ovary-biased and three testis-biased genes), whereas two genes showed no difference between ovary and testis. Further investigation of 12 selected sexually dimorphic Fox genes showed changes in the expression profile of 11 genes in the ovary of larvae reared at high temperatures (28°C). The results of the present study provide information on Fox genes in an amphibian and suggest that they play key roles in sexual development and reproduction in A. davidianus.

Genome-Wide Identification and Characterization of Fox Genes in the Honeybee, Apis cerana, and Comparative Analysis with Other Bee Fox Genes

The forkhead box (Fox) gene family, one of the most important families of transcription factors, participates in various biological processes. However, Fox genes in Hymenoptera are still poorly known. In this study, 14 Fox genes were identified in the genome of Apis cerana. In addition, 16 (Apis mellifera), 13 (Apis dorsata), 16 (Apis florea), 17 (Bombus terrestris), 16 (Bombus impatiens), and 18 (Megachile rotundata) Fox genes were identified in their genomes, respectively. Phylogenetic analyses suggest that FoxA is absent in the genome of A. dorsata genome. Similarly, FoxG is missing in the genomes A. cerana and A. dorsata. Temporal expression profiles obtained by quantitative real-time PCR revealed that Fox genes have distinct expression patterns in A. cerana, especially for three genes ACSNU03719T0 (AcFoxN4), ACSNU05765T0 (AcFoxB), and ACSNU07465T0 (AcFoxL2), which displayed high expression at the egg stage. Tissue expression patterns showed that FoxJ1 is significantly higher in the antennae of A. cerana and A. mellifera compared to other tissues. These results may facilitate a better understanding of the potential physiological functions of the Fox gene family in A. cerana and provide valuable information for a comprehensive functional analysis of the Fox gene family in Hymenopterans.

Crosstalk between microRNA-122 and FOX family genes in HepG2 cells

MicroRNA-122 (miR-122) is liver specific and plays an important role in physiology as well as diseases including hepatocellular carcinoma (HCC). Downregulation of miR-122 in HCC modulates apoptosis. Similarly, the putative targets of miR-122, the forkhead box (FOX) family genes also play an important role in the regulation of apoptosis. Hence, an interplay between miR-122 and FOX family genes has been explored in this study. Initially, an augmentation of apoptosis was noticed in HepG2 cells after transfection with miR-122. Further, the predicted miR-122 targets, the FOX family genes ( FOXM1b, FOXP1, and FOXO4) were selected via in silico analysis based on their role in apoptosis. We checked the expression of all these genes at transcript level after the transfection of miR-122 and found that the relative expression of FOXP1 and FOXM1b was significantly downregulated (p < 0.005) and that of FOXO4 was upregulated (p < 0.005). Thus, the finding indicates deregulation of these FOX genes as a result of miR-122 augmentation might be involved in the modulation of apoptosis. Impact Statement Here, we have investigated the crosstalk between microRNA-122 (miR-122) and selective FOX family genes in HepG2 cells. miR-122 is a prominent miRNA in liver and has been reported to be downregulated in hepatocellular carcinoma (HCC). It has been speculated that diminished level of miR-122 during HCC might be one of the reasons for tumor progression. However, the exact molecular interactions are not clear yet. This study unravels one of the molecular mechanisms of miR-122 through which it might impact the tumorigenesis of HCC.