scholarly journals Haploinsufficiency of Homeodomain Proteins Six3, Vax1, and Otx2 Causes Subfertility in Mice via Distinct Mechanisms

2018 ◽  
Vol 109 (3) ◽  
pp. 200-207 ◽  
Author(s):  
Hanne M. Hoffmann ◽  
Erica C. Pandolfi ◽  
Rachel Larder ◽  
Pamela L. Mellon
Keyword(s):  
Single Copy ◽  
Normal Activity ◽  
Homeodomain Proteins ◽  
Olfactory Placode ◽  
Complex Process ◽  
Gnrh Neurons ◽  
And Function

Haploinsufficiency occurs when loss of one copy of a diploid gene (hemizygosity) causes a phenotype. It is relatively rare, in that most genes can produce sufficient mRNA and protein from a single copy to prevent any loss of normal activity and function. Reproduction is a complex process relying on migration of GnRH neurons from the olfactory placode to the hypothalamus during development. We have studied 3 different homeodomain genes Otx2, Vax1, and Six3 and found that the deletion of one allele for any of these genes in mice produces subfertility or infertility in one or both sexes, despite the presence of one intact allele. All 3 heterozygous mice have reduced numbers of GnRH neurons, but the mechanisms of subfertility differ significantly. This review compares the subfertility phenotypes and their mechanisms.

Yeast ribosomal protein L1 is required for the stability of newly synthesized 5S rRNA and the assembly of 60S ribosomal subunits

1993 ◽  
Vol 13 (5) ◽  
pp. 2835-2845
Author(s):  
M Deshmukh ◽  
Y F Tsay ◽  
A G Paulovich ◽  
J L Woolford
Keyword(s):  
Ribosomal Protein ◽  
Ribosomal Subunit ◽  
Single Copy ◽  
5S Rrna ◽  
Gene Encoding ◽  
Ribosomal Subunits ◽  
Ribosomal Protein L1 ◽  
The Stability ◽  
And Function

Ribosomal protein L1 from Saccharomyces cerevisiae binds 5S rRNA and can be released from intact 60S ribosomal subunits as an L1-5S ribonucleoprotein (RNP) particle. To understand the nature of the interaction between L1 and 5S rRNA and to assess the role of L1 in ribosome assembly and function, we cloned the RPL1 gene encoding L1. We have shown that RPL1 is an essential single-copy gene. A conditional null mutant in which the only copy of RPL1 is under control of the repressible GAL1 promoter was constructed. Depletion of L1 causes instability of newly synthesized 5S rRNA in vivo. Cells depleted of L1 no longer assemble 60S ribosomal subunits, indicating that L1 is required for assembly of stable 60S ribosomal subunits but not 40S ribosomal subunits. An L1-5S RNP particle not associated with ribosomal particles was detected by coimmunoprecipitation of L1 and 5S rRNA. This pool of L1-5S RNP remained stable even upon cessation of 60S ribosomal subunit assembly by depletion of another ribosomal protein, L16. Preliminary results suggest that transcription of RPL1 is not autogenously regulated by L1.

Evolution and function of tandem repeats in the major surface protein 1a of the ehrlichial pathogenAnaplasma marginale

2001 ◽  
Vol 2 (2) ◽  
pp. 163-174 ◽  
Author(s):  
José de la Fuente ◽  
Jose C. Garcia-Garcia ◽  
Edmour F. Blouin ◽  
Sergio D. Rodríguez ◽  
Migel A. García ◽  
...  
Keyword(s):  
Tandem Repeats ◽  
Control Strategies ◽  
Surface Protein ◽  
Single Copy ◽  
Major Surface Protein ◽  
Host Parasite Interactions ◽  
Major Surface ◽  
And Function ◽  
Host Parasite ◽  
Bovine Erythrocytes

AbstractThe major surface protein (MSP) 1a of the ehrlichial cattle pathogenAnaplasma marginale, encoded by the single-copy genemsp1α, has been shown to have a neutralization-sensitive epitope and to be an adhesin for bovine erythrocytes and tick cells.msp1αhas been found to be a stable genetic marker for the identification of geographic isolates ofA. marginalethroughout development in acutely and persistently infected cattle and in ticks. The molecular weight of MSP1a varies among geographic isolates ofA. marginalebecause of a varying number of tandemly repeated peptides of 28–29 amino acids. Variation in the sequence of the tandem repeats occurs within and among isolates, and may have resulted from evolutionary pressures exerted by ligand–receptor and host–parasite interactions. These repeated sequences include markers for tick transmissibility that may be important in the identification of ehrlichial pathogens because they may influence control strategies and the design of subunit vaccines.

scholarly journals Genome Analyses and Genome-Centered Metatranscriptomics of Methanothermobacter wolfeii Strain SIV6, Isolated from a Thermophilic Production-Scale Biogas Fermenter

2019 ◽  
Vol 8 (1) ◽  
pp. 13
Author(s):  
Julia Hassa ◽  
Daniel Wibberg ◽  
Irena Maus ◽  
Alfred Pühler ◽  
Andreas Schlüter
Keyword(s):  
Microbial Community ◽  
Biogas Production ◽  
Gc Content ◽  
Production Scale ◽  
Circular Chromosome ◽  
Hydrogenotrophic Methanogenesis ◽  
Complex Process ◽  
Indigenous Microbial Community ◽  
Genome Analyses ◽  
And Function

In the thermophilic biogas-producing microbial community, the genus Methanothermobacter was previously described to be frequently abundant. The aim of this study was to establish and analyze the genome sequence of the archaeal strain Methanothermobacter wolfeii SIV6 originating from a thermophilic industrial-scale biogas fermenter and compare it to related reference genomes. The circular chromosome has a size of 1,686,891 bases, featuring a GC content of 48.89%. Comparative analyses considering three completely sequenced Methanothermobacter strains revealed a core genome of 1494 coding sequences and 16 strain specific genes for M. wolfeii SIV6, which include glycosyltransferases and CRISPR/cas associated genes. Moreover, M. wolfeii SIV6 harbors all genes for the hydrogenotrophic methanogenesis pathway and genome-centered metatranscriptomics indicates the high metabolic activity of this strain, with 25.18% of all transcripts per million (TPM) belong to the hydrogenotrophic methanogenesis pathway and 18.02% of these TPM exclusively belonging to the mcr operon. This operon encodes the different subunits of the enzyme methyl-coenzyme M reductase (EC: 2.8.4.1), which catalyzes the final and rate-limiting step during methanogenesis. Finally, fragment recruitment of metagenomic reads from the thermophilic biogas fermenter on the SIV6 genome showed that the strain is abundant (1.2%) within the indigenous microbial community. Detailed analysis of the archaeal isolate M. wolfeii SIV6 indicates its role and function within the microbial community of the thermophilic biogas fermenter, towards a better understanding of the biogas production process and a microbial-based management of this complex process.

In Silico Analysis of Non Synonymous Single Nucleotide Polymorphisms (nsSNPs) of SMPX Gene in Hearing Impairment

2018 ◽  
Author(s):  
Md. Arifuzzaman ◽  
Sarmistha Mitra ◽  
Amir Hamza ◽  
Raju Das ◽  
Nurul Absar ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Protein Stability ◽  
In Silico Analysis ◽  
Normal Activity ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Binding Motifs ◽  
Stability Change ◽  
And Function ◽  
Dbsnp Database

ABSTRACTBackgroundMutations in SMPX gene can disrupt the normal activity of the SMPX protein which is involved in hearing process.ObjectiveIn this study, deleterious non-synonymous single nucleotide polymorphisms were isolated from the neutral variants by using several bioinformatics tools.MethodFirstly, dbSNP database hosted by NCBI was used to retrieve the SNPs of SMPX gene, secondly, SIFT was used primarily to screen the damaging SNPs. Further, for validation PROVEAN, PredictSNP and PolyPhen 2 were used. I-Mutant 3 was utilized to analyze the protein stability change and MutPred predicted the molecular mechanism of protein stability change. Finally evolutionary conservation was done to study their conservancy by using ConSurf server.ResultsA total of 26 missense (0.6517%) and 3 nonsense variants (0.075%) were retrieved and among them 4 mutations were found deleterious by all the tools of this experiment and are also highly conserved according to ConSurf server. rs772775896, rs759552778, rs200892029 and rs1016314772 are the reference IDs of deleterious mutations where the substitutions are S71L, N19D, A29T and K54N. Loss of Ubiquitination, loss of methylation, loss of glycosylation, and loss of MoRF binding motifs are the root causes of protein stability change.ConclusionThis is the first study regarding nsSNPs of SMPX gene where the most damaging SNPs were screened that are associated with the SMPX gene and can be used for further research to study their effect on protein structure and function, their dynamic behavior and how they actually affect protein’s flexibility.

scholarly journals Superoxide levels and function of cerebral blood vessels after inhibition of CuZn-SOD

2001 ◽  
Vol 281 (4) ◽  
pp. H1697-H1703 ◽  
Author(s):  
Sean P. Didion ◽  
Christopher A. Hathaway ◽  
Frank M. Faraci
Keyword(s):  
Nitric Oxide ◽  
Arachidonic Acid ◽  
Blood Vessels ◽  
Basilar Artery ◽  
Normal Activity ◽  
Cerebral Blood Vessels ◽  
Cranial Window ◽  
Copper Zinc ◽  
Cerebral Arterioles ◽  
And Function

The goal of this study was to examine the role of endogenous copper/zinc (CuZn)-superoxide dismutase (SOD) on superoxide levels and on responses of cerebral blood vessels to stimuli that are mediated by nitric oxide (acetylcholine) and cyclooxygenase-dependent mechanisms (bradykinin and arachidonic acid). Levels of superoxide in the rabbit basilar artery were measured using lucigenin-enhanced chemiluminescence (5 μM lucigenin). Diethyldithiocarbamate (DDC; 10 mM), an inhibitor of CuZn-SOD, increased superoxide levels by ∼2.4-fold ( P < 0.05) from a baseline value of 1.0 ± 0.2 relative light units · min−1 · mm−2(means ± SE). The diameter of cerebral arterioles (baseline diameter, 99 ± 3 μm) was also measured using a closed cranial window in anesthetized rabbits. Topical application of DDC attenuated responses to acetylcholine, bradykinin, and arachidonate, but not nitroprusside. For example, 10 μM arachidonic acid dilated cerebral arterioles by 40 ± 5 and 2 ± 2 μm under control conditions and after DDC, respectively ( P < 0.05). These inhibitory effects of DDC were reversed by the superoxide scavenger 4,5-dihydroxy-1,3-benzenedisulfonic acid (10 mM). Arachidonate increased superoxide levels in the basilar artery moderately under normal conditions and this increase was greatly augmented in the presence of DDC. These findings suggest that endogenous CuZn-SOD limits superoxide levels under basal conditions and has a marked influence on increases in superoxide in vessels exposed to arachidonic acid. The results also suggest that nitric oxide- and cyclooxygenase-mediated responses in the cerebral microcirculation are dependent on normal activity of CuZn-SOD.

The structure and function of the mouth parts of adult caddis flies (Trichoptera)

1957 ◽  
Vol 241 (677) ◽  
pp. 45-91 ◽  
Keyword(s):  
Blood Pressure ◽  
Comparative Study ◽  
Central Area ◽  
Normal Activity ◽  
Head Capsule ◽  
Structure And Function ◽  
Detailed Account ◽  
Anterior Surface ◽  
Caddis Flies ◽  
And Function

The paper gives a detailed account of the structure and function of the mouth parts of Phryganea striata L., followed by a comparative study of these structures throughout the order Trichoptera. Observations on the feeding of caddis flies are reviewed. Consideration is given to homologies and phylogeny. In Phryganea the head is produced ventrally into a proboscis to which all parts of the mouth complex contribute. A detailed account is given of external and internal structure, musculature, and nervous system of the head and mouth parts. The central area of the anterior surface of the head capsule is interpreted as a frontoclypeus because of the origin of muscles to the foregut. The elongate labrum covers a sclerotized groove or sitophore. Mandibles are reduced to small lobes. The cardines and stipites of the maxillae contribute to the base of the proboscis. The single maxillary lobe is interpreted as a lacinia on grounds of musculature. The distinctive protrusible haustellum is regarded as derived from the hypopharynx. It is traversed by a common salivary duct, provided with a muscular valve. The anterior surface of the haustellum is covered with a system of channels which converge to the sitophore. These channels are formed by cuticular outgrowths arranged in lines and drawn out into filaments which roof the channels thus formed. These outgrowths, which are named pectinate hairs, differ in form according to their position on the haustellum. The labium forms part of the base of the proboscis. There is no ligula. Extension of the proboscis is brought about both by muscle action on sclerites and increased blood pressure affecting the flexible areas of cuticle. Relaxation results from reduction in blood pressure, and contraction of retractor muscles. The haustellum functions as an organ for taking up liquids. A direct drinking and a lapping attitude are described. The comparative study includes observations on fifty-three species, which are representative of each of the thirteen families found in Britain. All species examined have a protrusible haustellum, and are capable of drinking. The most highly developed condition is seen in the Phryganeidae and Limnephilidae. A channelled haustellum is also found in the Sericostomatidae, Beraeidae, Molannidae, Odontoceridae, Leptoceridae and Polycentropidae. A simple granulose haustellar surface, devoid of channels, is present in the Hydropsychidae, Psychomyidae, Philopotamidae, Rhyacophilidae and Hydroptilidae. The mandibles are of doubtful function. They are largest in the Hydropsychidae and Rhyacophilidae, and most reduced in Limnephilidae. Small lobes, which are thought to represent the ligula of the labium, are seen in the Philopotamidae, Hydropsychidae, Psychomyidae and Polycentropidae. These differing conditions of the mouth parts are shown to accord with views on the phylogeny of the Trichoptera, which are derived from other data. An account is given of published descriptions of modified mouth parts in some exotic species. The nature of these modifications is discussed. Published observations on the feeding of caddis flies are reviewed. It is concluded that using the haustellum to drink nectar and water is a normal activity of caddis flies.

scholarly journals GCP5 and GCP6: Two New Members of the Human γ-Tubulin Complex

2001 ◽  
Vol 12 (11) ◽  
pp. 3340-3352 ◽  
Author(s):  
Steven M. Murphy ◽  
Andrea M. Preble ◽  
Urvashi K. Patel ◽  
Kathy L. O'Connell ◽  
D. Prabha Dias ◽  
...  
Keyword(s):  
Sequence Similarity ◽  
Single Copy ◽  
Mass Spectrometry Analysis ◽  
Subunit Structure ◽  
Microtubule Nucleation ◽  
New Members ◽  
Spectrometry Analysis ◽  
Multiple Copies ◽  
And Function

The γ-tubulin complex is a large multiprotein complex that is required for microtubule nucleation at the centrosome. Here we report the purification and characterization of the human γ-tubulin complex and the identification of its subunits. The human γ-tubulin complex is a ring of ∼25 nm, has a subunit structure similar to that reported for γ-tubulin complexes from other species, and is able to nucleate microtubule polymerization in vitro. Mass spectrometry analysis of the human γ-tubulin complex components confirmed the presence of four previously identified components (γ-tubulin and γ-tubulin complex proteins [GCPs] 2, 3, and 4) and led to the identification of two new components, GCP5 and GCP6. Sequence analysis revealed that the GCPs share five regions of sequence similarity and define a novel protein superfamily that is conserved in metazoans. GCP5 and GCP6, like other components of the γ-tubulin complex, localize to the centrosome and associate with microtubules, suggesting that the entire γ-tubulin complex takes part in both of these interactions. Stoichiometry experiments revealed that there is a single copy of GCP5 and multiple copies of γ-tubulin, GCP2, GCP3, and GCP4 within the γ-tubulin complex. Thus, the γ-tubulin complex is conserved in structure and function, suggesting that the mechanism of microtubule nucleation is conserved.

Regulation and function of homeodomain proteins in the embryonic and adult vascular systemsThis paper is one of a selection of papers published in this Special Issue, entitled Young Investigators' Forum.

2007 ◽  
Vol 85 (1) ◽  
pp. 55-65 ◽  
Author(s):  
Josette M. Douville ◽  
Jeffrey T. Wigle
Keyword(s):  
Transcription Factors ◽  
Target Genes ◽  
Vascular System ◽  
Homeobox Genes ◽  
Tube Formation ◽  
Binding Motif ◽  
Homeodomain Proteins ◽  
Downstream Target ◽  
Endothelial Tube Formation ◽  
And Function

During embryonic development, the cardiovascular system first forms and then gives rise to the lymphatic vascular system. Homeobox genes are essential for both the development of the blood and lymphatic vascular systems, as well as for their maintenance in the adult. These genes all encode proteins that are transcription factors that contain a well conserved DNA binding motif, the homeodomain. It is through the homeodomain that these transcription factors bind to the promoters of target genes and regulate their expression. Although many homeodomain proteins have been found to be expressed within the vascular systems, little is known about their downstream target genes. This review highlights recent advances made in the identification of novel genes downstream of the homeodomain proteins that are necessary for regulating vascular cellular processes such as proliferation, migration, and endothelial tube formation. Factors known to regulate the functions of vascular cells via modulating the expression of homeobox genes will be discussed. We will also review current methods used to identify and characterize downstream target genes of homeodomain proteins.

scholarly journals Identification and function of hypoxia-response genes in Drosophila melanogaster

2006 ◽  
Vol 25 (1) ◽  
pp. 134-141 ◽  
Author(s):  
Guowen Liu ◽  
Julianne Roy ◽  
Eric A. Johnson
Keyword(s):  
Recovery Time ◽  
Normal Activity ◽  
Mrna Levels ◽  
Low Oxygen ◽  
Hypoxia Response ◽  
Oxygen Treatment ◽  
Genome Wide ◽  
A Genome ◽  
And Function ◽  
Genome Wide Study

Hypoxia, an insufficient level of oxygen in the cell, occurs during normal activity and also in pathological conditions such as ischemia and tumorigenesis. Although many hypoxia-response genes have been identified, an understanding of the functional role for these genes in the living animal is lacking. Here we present a genome-wide study of gene expression changes during hypoxia and then functionally test a subset of these genes for roles in survival and recovery from hypoxia. We found 79 genes with increased mRNA levels when adult flies were treated with 0.5% O2 for 6 h. A subset of these genes had detectably increased levels in as short as 1 h of low-oxygen treatment. Mild hypoxia levels resulted in an increase in transcription levels for only 20 genes. Viability during hypoxia and recovery time from hypoxia-induced paralysis was examined in flies with a reduction in activity in hypoxia-response genes. The observed decreased viability and increased recovery time from paralysis in many of the lines demonstrate that the increased transcript levels seen after hypoxia are important for the response to low oxygen.

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