Wingless signaling in the Drosophila embryo: zygotic requirements and the role of the frizzled genes

Development ◽  
1999 ◽  
Vol 126 (3) ◽  
pp. 577-586 ◽  
Author(s):  
H. Muller ◽  
R. Samanta ◽  
E. Wieschaus
Keyword(s):  
Genomic Region ◽  
Drosophila Embryo ◽  
Surface Molecules ◽  
New Genes ◽  
Wingless Signaling ◽  
Frizzled Receptors ◽  
Signaling Receptors ◽  
Genomic Regions ◽  
High Degree

Wingless signaling plays a central role during epidermal patterning in Drosophila. We have analyzed zygotic requirements for Wingless signaling in the embryonic ectoderm by generating synthetic deficiencies that uncover more than 99% of the genome. We found no genes required for initial wingless expression, other than previously identified segmentation genes. In contrast, maintenance of wingless expression shows a high degree of zygotic transcriptional requirements. Besides known genes, we have identified at least two additional genomic regions containing new genes involved in Wingless maintenance. We also assayed for the zygotic requirements for Wingless response and found that no single genomic region was required for the cytoplasmic accumulation of Armadillo in the receiving cells. Surprisingly, embryos homozygously deleted for the candidate Wingless receptor, Dfrizzled2, showed a normal Wingless response. However, the Armadillo response to Wingless was strongly reduced in double mutants of both known members of the frizzled family in Drosophila, frizzled and Dfrizzled2. Based on their expression pattern during embryogenesis, different Frizzled receptors may play unique but overlapping roles in development. In particular, we suggest that Frizzled and Dfrizzled2 are both required for Wingless autoregulation, but might be dispensable for late Engrailed maintenance. While Wingless signaling in embryos mutant for frizzled and Dfrizzled2 is affected, Wingless protein is still internalized into cells adjacent to wingless-expressing cells. Incorporation of Wingless protein may therefore involve cell surface molecules in addition to the genetically defined signaling receptors of the frizzled family.

scholarly journals Critical Role of Dispensable Genes in Mycoplasma agalactiae Interaction with Mammalian Cells

2010 ◽  
Vol 78 (4) ◽  
pp. 1542-1551 ◽  
Author(s):  
Eric Baranowski ◽  
Sébastien Guiral ◽  
Eveline Sagné ◽  
Agnès Skapski ◽  
Christine Citti
Keyword(s):  
Hela Cells ◽  
Mammalian Cells ◽  
Critical Role ◽  
Genomic Region ◽  
Mycoplasma Agalactiae ◽  
Transposon Insertion ◽  
Mammalian Cell Lines ◽  
Fold Reduction ◽  
Genomic Regions

ABSTRACT Mycoplasmas are minimal bacteria whose genomes barely exceed the smallest amount of information required to sustain autonomous life. Despite this apparent simplicity, several mycoplasmas are successful pathogens of humans and animals, in which they establish intimate interactions with epithelial cells at mucosal surfaces. To identify biological functions mediating mycoplasma interactions with mammalian cells, we produced a library of transposon knockout mutants in the ruminant pathogen Mycoplasma agalactiae and used this library to identify mutants displaying a growth-deficient pheonotype in cell culture. M. agalactiae mutants displaying a 3-fold reduction in CFU titers to nearly complete extinction in coculture with HeLa cells were identified. Mapping of transposon insertion sites revealed 18 genomic regions putatively involved in the interaction of M. agalactiae with HeLa cells. Several of these regions encode proteins with features of membrane lipoproteins and/or were involved in horizontal gene transfer with phylogenetically distant pathogenic mycoplasmas of ruminants. Two mutants with the most extreme phenotype carry a transposon in a genomic region designated the NIF locus which encodes homologues of SufS and SufU, two proteins presumably involved in [Fe-S] cluster biosynthesis in Gram-positive bacteria. Complementation studies confirmed the conditional essentiality of the NIF locus, which was found to be critical for proliferation in the presence of HeLa cells and several other mammalian cell lines but dispensable for axenic growth. While our results raised questions regarding essential functions in mycoplasmas, they also provide a means for studying the role of mycoplasmas as minimal pathogens.

scholarly journals Accumulation of transposable elements in Hox gene clusters during adaptive radiation of Anolis lizards

2016 ◽  
Vol 283 (1840) ◽  
pp. 20161555 ◽  
Author(s):  
Nathalie Feiner
Keyword(s):  
Transposable Elements ◽  
Dna Sequences ◽  
Adaptive Radiation ◽  
Genome Structure ◽  
Gene Clusters ◽  
Genomic Region ◽  
High Rate ◽  
Morphological Adaptations ◽  
Genomic Regions

Transposable elements (TEs) are DNA sequences that can insert elsewhere in the genome and modify genome structure and gene regulation. The role of TEs in evolution is contentious. One hypothesis posits that TE activity generates genomic incompatibilities that can cause reproductive isolation between incipient species. This predicts that TEs will accumulate during speciation events. Here, I tested the prediction that extant lineages with a relatively high rate of speciation have a high number of TEs in their genomes. I sequenced and analysed the TE content of a marker genomic region ( Hox clusters) in Anolis lizards, a classic case of an adaptive radiation. Unlike other vertebrates, including closely related lizards, Anolis lizards have high numbers of TEs in their Hox clusters, genomic regions that regulate development of the morphological adaptations that characterize habitat specialists in these lizards. Following a burst of TE activity in the lineage leading to extant Anolis , TEs have continued to accumulate during or after speciation events, resulting in a positive relationship between TE density and lineage speciation rate. These results are consistent with the prediction that TE activity contributes to adaptive radiation by promoting speciation. Although there was no evidence that TE density per se is associated with ecological morphology, the activity of TEs in Hox clusters could have been a rich source for phenotypic variation that may have facilitated the rapid parallel morphological adaptation to microhabitats seen in extant Anolis lizards.

scholarly journals The Power of Yeast in Modelling Human Nuclear Mutations Associated with Mitochondrial Diseases

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 300
Author(s):  
Camilla Ceccatelli Berti ◽  
Giulia di Punzio ◽  
Cristina Dallabona ◽  
Enrico Baruffini ◽  
Paola Goffrini ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Mitochondrial Diseases ◽  
Yeast Saccharomyces Cerevisiae ◽  
Genome Data ◽  
New Genes ◽  
Eukaryotic Organism ◽  
Novel Variants ◽  
Therapeutic Molecules ◽  
Nuclear Mutations

The increasing application of next generation sequencing approaches to the analysis of human exome and whole genome data has enabled the identification of novel variants and new genes involved in mitochondrial diseases. The ability of surviving in the absence of oxidative phosphorylation (OXPHOS) and mitochondrial genome makes the yeast Saccharomyces cerevisiae an excellent model system for investigating the role of these new variants in mitochondrial-related conditions and dissecting the molecular mechanisms associated with these diseases. The aim of this review was to highlight the main advantages offered by this model for the study of mitochondrial diseases, from the validation and characterisation of novel mutations to the dissection of the role played by genes in mitochondrial functionality and the discovery of potential therapeutic molecules. The review also provides a summary of the main contributions to the understanding of mitochondrial diseases emerged from the study of this simple eukaryotic organism.

scholarly journals 3D reconstruction of genomic regions from sparse interaction data

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Julen Mendieta-Esteban ◽  
Marco Di Stefano ◽  
David Castillo ◽  
Irene Farabella ◽  
Marc A Marti-Renom
Keyword(s):  
3D Models ◽  
Genomic Region ◽  
Gene Promoters ◽  
Chromosome Conformation ◽  
The Matrix ◽  
Chromatin Structural ◽  
A Cell ◽  
Similar Accuracy ◽  
Genomic Regions ◽  
Interaction Matrices

Abstract Chromosome conformation capture (3C) technologies measure the interaction frequency between pairs of chromatin regions within the nucleus in a cell or a population of cells. Some of these 3C technologies retrieve interactions involving non-contiguous sets of loci, resulting in sparse interaction matrices. One of such 3C technologies is Promoter Capture Hi-C (pcHi-C) that is tailored to probe only interactions involving gene promoters. As such, pcHi-C provides sparse interaction matrices that are suitable to characterize short- and long-range enhancer–promoter interactions. Here, we introduce a new method to reconstruct the chromatin structural (3D) organization from sparse 3C-based datasets such as pcHi-C. Our method allows for data normalization, detection of significant interactions and reconstruction of the full 3D organization of the genomic region despite of the data sparseness. Specifically, it builds, with as low as the 2–3% of the data from the matrix, reliable 3D models of similar accuracy of those based on dense interaction matrices. Furthermore, the method is sensitive enough to detect cell-type-specific 3D organizational features such as the formation of different networks of active gene communities.

scholarly journals Roles of ncRNAs as ceRNAs in Gastric Cancer

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1036
Author(s):  
Junhong Ye ◽  
Jifu Li ◽  
Ping Zhao
Keyword(s):  
Gastric Cancer ◽  
Research Strategy ◽  
Circular Rnas ◽  
Messenger Rnas ◽  
Cerna Network ◽  
Degree Of Malignancy ◽  
High Degree ◽  
Competitive Endogenous Rna ◽  
Made In

Although ignored in the past, with the recent deepening of research, significant progress has been made in the field of non-coding RNAs (ncRNAs). Accumulating evidence has revealed that microRNA (miRNA) response elements regulate RNA. Long ncRNAs, circular RNAs, pseudogenes, miRNAs, and messenger RNAs (mRNAs) form a competitive endogenous RNA (ceRNA) network that plays an essential role in cancer and cardiovascular, neurodegenerative, and autoimmune diseases. Gastric cancer (GC) is one of the most common cancers, with a high degree of malignancy. Considerable progress has been made in understanding the molecular mechanism and treatment of GC, but GC’s mortality rate is still high. Studies have shown a complex ceRNA crosstalk mechanism in GC. lncRNAs, circRNAs, and pseudogenes can interact with miRNAs to affect mRNA transcription. The study of the involvement of ceRNA in GC could improve our understanding of GC and lead to the identification of potential effective therapeutic targets. The research strategy for ceRNA is mainly to screen the different miRNAs, lncRNAs, circRNAs, pseudogenes, and mRNAs in each sample through microarray or sequencing technology, predict the ceRNA regulatory network, and, finally, conduct functional research on ceRNA. In this review, we briefly discuss the proposal and development of the ceRNA hypothesis and the biological function and principle of ceRNAs in GC, and briefly introduce the role of ncRNAs in the GC’s ceRNA network.

scholarly journals Identification of Autosomal Regions Involved in Drosophila Raf Function

Genetics ◽  
2000 ◽  
Vol 156 (2) ◽  
pp. 763-774 ◽  
Author(s):  
Willis Li ◽  
Elizabeth Noll ◽  
Norbert Perrimon
Keyword(s):  
Limb Development ◽  
Target Gene ◽  
Biological Function ◽  
Genetic Interaction ◽  
Ectopic Expression ◽  
Tor Signaling ◽  
Downstream Effector ◽  
Early Embryos ◽  
Genomic Regions

Abstract Raf is an essential downstream effector of activated p21Ras (Ras) in transducing proliferation or differentiation signals. Following binding to Ras, Raf is translocated to the plasma membrane, where it is activated by a yet unidentified “Raf activator.” In an attempt to identify the Raf activator or additional molecules involved in the Raf signaling pathway, we conducted a genetic screen to identify genomic regions that are required for the biological function of Drosophila Raf (Draf). We tested a collection of chromosomal deficiencies representing ∼70% of the autosomal euchromatic genomic regions for their abilities to enhance the lethality associated with a hypomorphic viable allele of Draf, DrafSu2. Of the 148 autosomal deficiencies tested, 23 behaved as dominant enhancers of Draf  Su2, causing lethality in Draf  Su2 hemizygous males. Four of these deficiencies identified genes known to be involved in the Drosophila Ras/Raf (Ras1/Draf) pathway: Ras1, rolled (rl, encoding a MAPK), 14-3-3ϵ, and bowel (bowl). Two additional deficiencies removed the Drosophila Tec and Src homologs, Tec29A and Src64B. We demonstrate that Src64B interacts genetically with Draf and that an activated form of Src64B, when overexpressed in early embryos, causes ectopic expression of the Torso (Tor) receptor tyrosine kinase-target gene tailless. In addition, we show that a mutation in Tec29A partially suppresses a gain-of-function mutation in tor. These results suggest that Tec29A and Src64B are involved in Tor signaling, raising the possibility that they function to activate Draf. Finally, we discovered a genetic interaction between Draf  Su2 and Df(3L)vin5 that revealed a novel role of Draf in limb development. We find that loss of Draf activity causes limb defects, including pattern duplications, consistent with a role for Draf in regulation of engrailed (en) expression in imaginal discs.

Surgeon-performed Ultrasound for Primary Hyperparathyroidism

2013 ◽  
Vol 79 (7) ◽  
pp. 681-685 ◽  
Author(s):  
Worthington G. Schenk ◽  
John B. Hanks ◽  
Philip W. Smith
Keyword(s):  
Primary Hyperparathyroidism ◽  
Class 1 ◽  
Additional Imaging ◽  
Surgical Cure ◽  
Operative Findings ◽  
Enhanced Computed Tomography ◽  
High Degree ◽  
Tomography Scan ◽  
Parathyroid Imaging

The role of preoperative parathyroid imaging continues to evolve. This study evaluated whether surgeon-performed ultrasound (U/S) obviates the need for other imaging studies and leads to a focused exploration with a high degree of surgical success. From July 2010 to February 2012, 200 patients presenting with nonfamilial primary hyperparathyroidism underwent neck U/S in the surgeon's office. The U/S interpretation was classified as Class 1 if an adenoma was identified with high confidence, Class 2 if a possible but not definite enlarged gland was imaged, and Class 0 (zero) if no adenoma was identified. The findings were correlated with subsequent intra-operative findings. There were 144 Class 1 U/Ss (72%); of 132 patients coming to surgery, 96.2 per cent had surgical findings concordant with preoperative U/S and all had apparent surgical cure. Twenty-nine patients (14.5%) had Class 2 U/S; the 31 per cent confirmed false-positives in this group were usually colloid nodules. Fourteen of 27 with Class 0 U/S underwent surgery after being offered dynamically enhanced computed tomography scan. All 200 patients were apparent surgical cures. Surgeon-performed U/S is expedient, convenient, inexpensive, and accurate. A clearly identified adenoma can safely lead to a focused limited exploration and avoid additional imaging 93 per cent of the time.

The academic profession in Russia’s two capitals: The impact of 20 years of transition

2017 ◽  
Vol 16 (5) ◽  
pp. 626-644 ◽  
Author(s):  
Elizaveta Sivak ◽  
Maria Yudkevich
Keyword(s):  
Large Scale ◽  
Academic Career ◽  
Academic Profession ◽  
University Faculty ◽  
Key Characteristics ◽  
Personal Strain ◽  
High Degree ◽  
The Impact ◽  
Russian Universities

This paper studies the dynamics of key characteristics of the academic profession in Russia based on the analysis of university faculty in the two largest cities in Russia – Moscow and St Petersburg. We use data on Russian university faculty from two large-scale comparative studies of the academic profession (‘The Carnegie Study’ carried out in 1992 in 14 countries, including Russia, and ‘The Changing Academic Profession Study’, 2007–2012, with 19 participating countries and which Russia joined in 2012) to look at how faculty’s characteristics and attitudes toward different aspects of their academic life changed over 20 years (1992–2011) such as faculty’s views on reasons to leave or to stay at a university, on university’s management and the role of faculty in decision making. Using the example of universities in the two largest Russian cities, we demonstrate that the high degree of overall centralization of governance in Russian universities barely changed in 20 years. Our paper provides comparisons of teaching/research preferences and views on statements concerning personal strain associated with work, academic career perspectives, etc., not only in Russian universities between the years 1992 and 2012, but also in Russia and other ‘Changing Academic Profession’ countries.

Myocardial CO2 buffering: role of transmembrane transport of H+ or HCO3-ions

1976 ◽  
Vol 230 (4) ◽  
pp. 1037-1041 ◽  
Author(s):  
DR Strome ◽  
RL Clancy ◽  
NC Gonzalez
Keyword(s):  
Small Volume ◽  
Coronary Circulation ◽  
Myocardial Cell ◽  
Ringer Solution ◽  
Red Cells ◽  
Transmembrane Transport ◽  
High Degree

Isolated rabbit hearts were perfused with rabbit red cells suspended in Ringer solution. A small volume of perfusate was recirculated for 10 min at Pco2 of 33.4 +/- 0.9 or 150.8 +/- 7.5 mmHg. Hypercapnia resulted in an increase in perfusate HCO3- concentration that was smaller than that observed when isolated perfusate was equilibrated in vitro with the same CO2 tensions (delta HCO-3e = 1.6 mM, P less than 0.01). This difference is consistent with a net movement of HCO3- into or H+ out of the mycardial cell, and cannot be accounted for by dilution of HCO3- in the myocardial interstitium. Recirculation of perfusate through the coronary circulation at normal Pco2 for two consecutive 10-min periods was not followed by changes in perfusate HCO3- concentration. A high degree of correlation (r = 0.81) was observed between intracellular HCO-3e concentration and the corresponding delta HCO-3e in individual experiments. The results suggest that transmembrane exchange of H+ or HCO3- is a buffer mechanism for CO2 in the myocardial cell.

scholarly journals Mycobacterium tuberculosis adhesins: potential biomarkers as anti-tuberculosis therapeutic and diagnostic targets

Microbiology ◽  
2014 ◽  
Vol 160 (9) ◽  
pp. 1821-1831 ◽  
Author(s):  
Viveshree S. Govender ◽  
Saiyur Ramsugit ◽  
Manormoney Pillay
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Control Strategies ◽  
Host Cells ◽  
Tuberculosis Control ◽  
Surface Molecules ◽  
Host Pathogen Interaction ◽  
Bacterial Aggregation ◽  
Insight Into

Adhesion to host cells is a precursor to host colonization and evasion of the host immune response. Conversely, it triggers the induction of the immune response, a process vital to the host’s defence against infection. Adhesins are microbial cell surface molecules or structures that mediate the attachment of the microbe to host cells and thus the host–pathogen interaction. They also play a crucial role in bacterial aggregation and biofilm formation. In this review, we discuss the role of adhesins in the pathogenesis of the aetiological agent of tuberculosis, Mycobacterium tuberculosis. We also provide insight into the structure and characteristics of some of the characterized and putative M. tuberculosis adhesins. Finally, we examine the potential of adhesins as targets for the development of tuberculosis control strategies.

Sign in / Sign up

Export Citation Format

Share Document