scholarly journals Rare mutations in the complement regulatory gene CSMD1 are associated with male and female infertility

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Arthur S. Lee ◽  
Jannette Rusch ◽  
Ana C. Lima ◽  
Abul Usmani ◽  
Ni Huang ◽  
...  
Keyword(s):  
Breeding Success ◽  
Regulatory Gene ◽  
Regulatory Protein ◽  
Complement C3 ◽  
Double Knockout ◽  
Genetic Trait ◽  
Candidate Locus ◽  
Male And Female ◽  
Gonadal Dysfunction ◽  
Complex Genetic Trait

Abstract Infertility in men and women is a complex genetic trait with shared biological bases between the sexes. Here, we perform a series of rare variant analyses across 73,185 women and men to identify genes that contribute to primary gonadal dysfunction. We report CSMD1, a complement regulatory protein on chromosome 8p23, as a strong candidate locus in both sexes. We show that CSMD1 is enriched at the germ-cell/somatic-cell interface in both male and female gonads. Csmd1-knockout males show increased rates of infertility with significantly increased complement C3 protein deposition in the testes, accompanied by severe histological degeneration. Knockout females show significant reduction in ovarian quality and breeding success, as well as mammary branching impairment. Double knockout of Csmd1 and C3 causes non-additive reduction in breeding success, suggesting that CSMD1 and the complement pathway play an important role in the normal postnatal development of the gonads in both sexes.

scholarly journals Reproductive Isolation and Morphogenetic Evolution in Drosophila Analyzed by Breakage of Ethological Barriers

Genetics ◽  
1997 ◽  
Vol 147 (1) ◽  
pp. 231-242 ◽  
Author(s):  
Lucas Sánchez ◽  
Pedro Santamaria
Keyword(s):  
Reproductive Isolation ◽  
Germ Cells ◽  
Morphological Analysis ◽  
Seminal Fluid ◽  
Germ Line ◽  
Regulatory Gene ◽  
Motile Sperm ◽  
Male And Female ◽  
Drosophila Yakuba

Abstract This article reports the breaking of ethological barriers through the constitution of soma-germ line chimeras between species of the melanogaster subgroup of Drosophila, which are ethologically isolated. Female Drosophila yakuba and D. teissieri germ cells in a D. melanogaster ovary produced functional oocytes that, when fertilized by D. melanogaster sperm, gave rise to sterile yakuba-melanogaster andteissieri-melanogaster male and female hybrids. However, the erecta-melanogaster and orena-melanogaster hybrids were lethal, since female D. erecta and D. orena germ cells in a D. melanogaster ovary failed to form oocytes with the capacity to develop normally. This failure appears to be caused by an altered interaction between the melanogaster soma and the erecta and orena germ lines. Germ cells of D. teissieri and D. orena in a D. melanogaster testis produced motile sperm that was not stored in D. melanogaster females. This might be due to incompatibility between the teissieri and orena sperm and the melanogaster seminal fluid. A morphological analysis of the terminalia of yakuba-melanogaster and teissieri-melanogaster hybrids was performed. The effect on the terminalia of teissieri-melanogaster hybrids of a mutation in doublesex, a regulatory gene that controls the development of the terminalia, was also investigated.

scholarly journals Potato Virus X-induced LeHB-1 Silencing Delays Tomato Fruit Ripening

2018 ◽  
Vol 143 (6) ◽  
pp. 454-461 ◽  
Author(s):  
Xiaohong Wang ◽  
Bishun Ye ◽  
Xiangpeng Kang ◽  
Ting Zhou ◽  
Tongfei Lai
Keyword(s):  
Potato Virus ◽  
Fruit Ripening ◽  
Ph Value ◽  
Tomato Fruit ◽  
Potato Virus X ◽  
Anthocyanin Content ◽  
Genetic Trait ◽  
Tomato Fruit Ripening ◽  
Homeobox Protein ◽  
Complex Genetic Trait

Tomato (Solanum lycopersicum) fruit ripening is a complex genetic trait correlating with notable fruit phenotypic, physiologic, and biochemical changes. Transcription factors (TFs) play crucial roles during this process. LeHB-1, an HD-zip homeobox protein, is a ripening-related TF and acts as an important regulator of fruit ripening. However, the detailed biochemical and molecular basis of LeHB-1 on tomato fruit ripening is unclear. In the current study, the biologic functions of LeHB-1 were determined by a potato virus X (PVX)-mediated gene-silencing approach. The results indicate that PVX-induced LeHB-1 silencing in tomato could decrease pigment accumulation and delay fruit ripening. Compared with controls, nonripening flesh retains a greater pH value and a lesser anthocyanin content. By evaluating expression levels of genes related to tomato fruit ripening, we inferred that LeHB-1 located at the downstream of LeMADS-RIN-mediated regulatory network. In addition, LeHB-1 silencing mainly disturbed phytoene desaturation and isomerization, and led to a decrease in trans-lycopene accumulation, but did not influence flavonoid biosynthesis directly in tomato fruit. The findings provide a theoretical foundation for illustrating the biologic functions of LeHB-1 in tomato fruit ripening and quality.

Repeated Family of Genes Controlling Maltose Fermentation in Saccharomyces carlsbergensis

1983 ◽  
Vol 3 (5) ◽  
pp. 796-802
Author(s):  
Richard B. Needleman ◽  
Corinne Michels
Keyword(s):  
Genetic Analysis ◽  
Structural Gene ◽  
Regulatory Gene ◽  
Regulatory Protein ◽  
Physical Analysis ◽  
Saccharomyces Carlsbergensis ◽  
Maltose Permease ◽  
Maltose Fermentation ◽  
Complex Locus ◽  
Dna Fragment

Maltose fermentation in Saccharomyces spp. requires the presence of any one of five unlinked genes: MAL1, MAL2, MAL3, MAL4 , or MAL6. Although the genes are functionally equivalent, their natures and relationships to each other are not known. At least three proteins are necessary for maltose fermentation: maltase, maltose permease, and a regulatory protein. The MAL genes may code for one or more of these proteins. Recently a DNA fragment containing a maltase structural gene has been cloned from a MAL6 strain, CB11, to produce plasmid pMAL9-26. We have conducted genetic and physical analyses of strain CB11. The genetic analysis has demonstrated the presence of two cryptic MAL genes in CB11, MAL1g and MAL3g (linked to MAL1 and to MAL3 , respectively), in addition to the MAL6 locus. The physical analysis, which used a subclone of plasmid pMAL9-26 as a probe, detected three Hin dIII genomic fragments with homology to the probe. Each fragment was shown to be linked to one of the MAL loci genetically demonstrated to be present in CB11. Our results indicate that the cloned maltase structural gene in plasmid pMAL9-26 is linked to MAL6. Since the MAL6 locus has previously been shown to contain a regulatory gene, the MAL6 locus must be a complex locus containing at least two of the factors needed for maltose fermentation: the structural gene for maltase and the maltase regulatory protein. The absence of other fragments which hybridize to the MAL6 -derived probe shows that either MAL2 and MAL4 are not related to MAL6 , or the DNA corresponding to these genes is absent from the MAL6 strain CB11.

scholarly journals Characterization of the Noncanonical Regulatory and Transporter Genes in Atratumycin Biosynthesis and Production in a Heterologous Host

Marine Drugs ◽  
2019 ◽  
Vol 17 (10) ◽  
pp. 560 ◽  
Author(s):  
Zhijie Yang ◽  
Xin Wei ◽  
Jianqiao He ◽  
Changli Sun ◽  
Jianhua Ju ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Streptomyces Coelicolor ◽  
Regulatory Gene ◽  
Regulatory Protein ◽  
Biosynthetic Gene Cluster ◽  
Negative Regulator ◽  
Over Expression ◽  
Lead Compounds ◽  
Mycobacteria Tuberculosis ◽  
Abc Transporter Genes

Atratumycin is a cyclodepsipeptide with activity against Mycobacteria tuberculosis isolated from deep-sea derived Streptomyces atratus SCSIO ZH16NS-80S. Analysis of the atratumycin biosynthetic gene cluster (atr) revealed that its biosynthesis is regulated by multiple factors, including two LuxR regulatory genes (atr1 and atr2), two ABC transporter genes (atr29 and atr30) and one Streptomyces antibiotic regulatory gene (atr32). In this work, three regulatory and two transporter genes were unambiguously determined to provide positive, negative and self-protective roles during biosynthesis of atratumycin through bioinformatic analyses, gene inactivations and trans-complementation studies. Notably, an unusual Streptomyces antibiotic regulatory protein Atr32 was characterized as a negative regulator; the function of Atr32 is distinct from previous studies. Five over-expression mutant strains were constructed by rational application of the regulatory and transporter genes; the resulting strains produced significantly improved titers of atratumycin that were ca. 1.7–2.3 fold greater than wild-type (WT) producer. Furthermore, the atratumycin gene cluster was successfully expressed in Streptomyces coelicolor M1154, thus paving the way for the transfer and recombination of large DNA fragments. Overall, this finding sets the stage for understanding the unique biosynthesis of pharmaceutically important atratumycin and lays the foundation for generating anti-tuberculosis lead compounds possessing novel structures.

scholarly journals Identification of Potential Novel Interacting Partners for Coagulation Factor XIII B (FXIII-B) Subunit, a Protein Associated with a Rare Bleeding Disorder

2019 ◽  
Vol 20 (11) ◽  
pp. 2682 ◽  
Author(s):  
Sneha Singh ◽  
Mohammad Suhail Akhter ◽  
Johannes Dodt ◽  
Peter Volkers ◽  
Andreas Reuter ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Regulatory Protein ◽  
Coagulation Factor ◽  
Factor H ◽  
Complement C3 ◽  
Complement Factor ◽  
B Subunit ◽  
Coagulation Factor Xiii ◽  
A Subunit ◽  
Complement C1q

Coagulation factor XIII (FXIII) is a plasma-circulating heterotetrameric pro-transglutaminase complex that is composed of two catalytic FXIII-A and two protective/regulatory FXIII-B subunits. FXIII acts by forming covalent cross-links within a preformed fibrin clots to prevent its premature fibrinolysis. The FXIII-A subunit is known to have pleiotropic roles outside coagulation, but the FXIII-B subunit is a relatively unexplored entity, both structurally as well as functionally. Its discovered roles so far are limited to that of the carrier/regulatory protein of its partner FXIII-A subunit. In the present study, we have explored the co-presence of protein excipients in commercial FXIII plasma concentrate FibrogamminP by combination of protein purification and mass spectrometry-based verification. Complement factor H was one of the co-excipients observed in this analysis. This was followed by performing pull down assays from plasma in order to detect the putative novel interacting partners for the FXIII-B subunit. Complement system proteins, like complement C3 and complement C1q, were amongst the proteins that were pulled down. The only protein that was observed in both experimental set ups was alpha-2-macroglobulin, which might therefore be a putative interacting partner of the FXIII/FXIII-B subunit. Future functional investigations will be needed to understand the physiological significance of this association.

scholarly journals Repeated Family of Genes Controlling Maltose Fermentation inSaccharomyces carlsbergensis

1983 ◽  
Vol 3 (5) ◽  
pp. 796-802 ◽  
Author(s):  
Richard B. Needleman ◽  
Corinne Michels
Keyword(s):  
Genetic Analysis ◽  
Structural Gene ◽  
Regulatory Gene ◽  
Regulatory Protein ◽  
Physical Analysis ◽  
Maltose Permease ◽  
Maltose Fermentation ◽  
Complex Locus ◽  
Dna Fragment

Maltose fermentation inSaccharomycesspp. requires the presence of any one of five unlinked genes:MAL1, MAL2, MAL3, MAL4, orMAL6.Although the genes are functionally equivalent, their natures and relationships to each other are not known. At least three proteins are necessary for maltose fermentation: maltase, maltose permease, and a regulatory protein. TheMALgenes may code for one or more of these proteins. Recently a DNA fragment containing a maltase structural gene has been cloned from aMAL6strain, CB11, to produce plasmid pMAL9-26. We have conducted genetic and physical analyses of strain CB11. The genetic analysis has demonstrated the presence of two crypticMALgenes in CB11,MAL1gandMAL3g(linked toMAL1and toMAL3, respectively), in addition to theMAL6locus. The physical analysis, which used a subclone of plasmid pMAL9-26 as a probe, detected threeHindIII genomic fragments with homology to the probe. Each fragment was shown to be linked to one of theMALloci genetically demonstrated to be present in CB11. Our results indicate that the cloned maltase structural gene in plasmid pMAL9-26 is linked toMAL6.Since theMAL6locus has previously been shown to contain a regulatory gene, theMAL6locus must be a complex locus containing at least two of the factors needed for maltose fermentation: the structural gene for maltase and the maltase regulatory protein. The absence of other fragments which hybridize to theMAL6-derived probe shows that eitherMAL2andMAL4are not related toMAL6, or the DNA corresponding to these genes is absent from theMAL6strain CB11.

Developmental and sex differences in cardiac tolerance to ischemia–reperfusion injury: the role of mitochondria

2019 ◽  
Vol 97 (9) ◽  
pp. 808-814 ◽  
Author(s):  
B. Ostadal ◽  
Z. Drahota ◽  
J. Houstek ◽  
M. Milerova ◽  
I. Ostadalova ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Regulatory Protein ◽  
Lower Sensitivity ◽  
Cyclophilin D ◽  
Male And Female ◽  
Postnatal Maturation ◽  
High Calcium ◽  
Age And Sex

Age and sex play an essential role in the cardiac tolerance to ischemia–reperfusion injury: cardiac resistance significantly decreases during postnatal maturation and the female heart is more tolerant than the male myocardium. It is widely accepted that mitochondrial dysfunction, and particularly mitochondrial permeability transition pore (MPTP) opening, plays a major role in determining the extent of cardiac ischemia–reperfusion injury. We have observed that the MPTP sensitivity to the calcium load differs in mitochondria isolated from neonatal and adult myocardium, as well as from adult male and female hearts. Neonatal and female mitochondria are more resistant both in the extent and in the rate of mitochondrial swelling induced by high calcium concentration. Our data further suggest that age- and sex-dependent specificity of the MPTP is not the result of different amounts of ATP synthase and cyclophilin D: neonatal and adult hearts, similarly as the male and female hearts, contain comparable amounts of MPTP and its regulatory protein cyclophilin D. We can speculate that the lower sensitivity of MPTP to the calcium-induced swelling may be related to the higher ischemic tolerance of both neonatal and female myocardium.

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