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The significance of clubbed antennae in grasshoppers was assessed by investigating the sensilla repertoire of 15 gomphocerine species. The influence of the diet type (graminivorous or polyphagous) and the apical thickening of antenna on the number of sensilla were tested. It appears that the antennal thickening has a stronger impact on the number of sensilla than the food mode. The species bearing clubbed antennae are globally low in olfactive and contact sensilla, maybe in relation with a more complex courtship, but are richer in mechanoreceptors, probably involved in the control of antenna movements. The food mode change from oligophagy to polyphagy is not associated to an increase in the number of olfactive or contact sensilla. In contrast, the high number of these sensilla in a monophagous grasshopper feeding on Ulex bushes is interpreted in the context of alkaloid detection. 相似文献
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Omar Soukarieh Pascaline Gaildrat Mohamad Hamieh Aurélie Drouet Stéphanie Baert-Desurmont Thierry Frébourg Mario Tosi Alexandra Martins 《PLoS genetics》2016,12(1)
The identification of a causal mutation is essential for molecular diagnosis and clinical management of many genetic disorders. However, even if next-generation exome sequencing has greatly improved the detection of nucleotide changes, the biological interpretation of most exonic variants remains challenging. Moreover, particular attention is typically given to protein-coding changes often neglecting the potential impact of exonic variants on RNA splicing. Here, we used the exon 10 of MLH1, a gene implicated in hereditary cancer, as a model system to assess the prevalence of RNA splicing mutations among all single-nucleotide variants identified in a given exon. We performed comprehensive minigene assays and analyzed patient’s RNA when available. Our study revealed a staggering number of splicing mutations in MLH1 exon 10 (77% of the 22 analyzed variants), including mutations directly affecting splice sites and, particularly, mutations altering potential splicing regulatory elements (ESRs). We then used this thoroughly characterized dataset, together with experimental data derived from previous studies on BRCA1, BRCA2, CFTR and NF1, to evaluate the predictive power of 3 in silico approaches recently described as promising tools for pinpointing ESR-mutations. Our results indicate that ΔtESRseq and ΔHZEI-based approaches not only discriminate which variants affect splicing, but also predict the direction and severity of the induced splicing defects. In contrast, the ΔΨ-based approach did not show a compelling predictive power. Our data indicates that exonic splicing mutations are more prevalent than currently appreciated and that they can now be predicted by using bioinformatics methods. These findings have implications for all genetically-caused diseases. 相似文献
4.
Yahui Liu Arsen Petrovic Pascaline Rombaut Shyamal Mosalaganti Jenny Keller Stefan Raunser Franz Herzog Andrea Musacchio 《Open biology》2016,6(2)
Accurate chromosome segregation during mitosis and meiosis is crucial for cellular and organismal viability. Kinetochores connect chromosomes with spindle microtubules and are essential for chromosome segregation. These large protein scaffolds emerge from the centromere, a specialized region of the chromosome enriched with the histone H3 variant CENP-A. In most eukaryotes, the kinetochore core consists of the centromere-proximal constitutive centromere-associated network (CCAN), which binds CENP-A and contains 16 subunits, and of the centromere-distal Knl1 complex, Mis12 complex, Ndc80 complex (KMN) network, which binds microtubules and contains 10 subunits. In the fruitfly, Drosophila melanogaster, the kinetochore underwent remarkable simplifications. All CCAN subunits, with the exception of centromeric protein C (CENP-C), and two KMN subunits, Dsn1 and Zwint, cannot be identified in this organism. In addition, two paralogues of the KMN subunit Nnf1 (Nnf1a and Nnf1b) are present. Finally, the Spc105R subunit, homologous to human Knl1/CASC5, underwent considerable sequence changes in comparison with other organisms. We combined biochemical reconstitution with biophysical and structural methods to investigate how these changes reflect on the organization of the Drosophila KMN network. We demonstrate that the Nnf1a and Nnf1b paralogues are subunits of distinct complexes, both of which interact directly with Spc105R and with CENP-C, for the latter of which we identify a binding site on the Mis12 subunit. Our studies shed light on the structural and functional organization of a highly divergent kinetochore particle. 相似文献
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Frédégonde About Tiphaine Oudot-Mellakh Jonathan Niay Pascaline Rabiéga Vincent Pedergnana Darragh Duffy Philippe Sultanik Carole Cagnot Fabrice Carrat Patrick Marcellin Fabien Zoulim Dominique Larrey Christophe Hézode Hélène Fontaine Jean-Pierre Bronowicki Stanislas Pol Matthew L. Albert Ioannis Theodorou Aurélie Cobat Laurent Abel ANRS CO-CUPIC study group 《PloS one》2015,10(12)
Background
Human genetic factors influence the outcome of pegylated interferon and ribavirin hepatitis C therapy. We explored the role of IL28B, APOH and ITPA SNPs on the outcomes of triple therapy including telaprevir or boceprevir in patients with compensated cirrhosis chronically infected with HCV-1.Patients and Methods
A total of 256 HCV-1 Caucasian treatment-experienced patients with compensated cirrhosis from the ANRS CO20-CUPIC cohort were genotyped for a total of 10 candidate SNPs in IL28B (rs12979860 and rs368234815), APOH (rs8178822, rs12944940, rs10048158, rs52797880, rs1801689 and rs1801690) and ITPA (rs1127354 and rs7270101). We tested the association of IL28B and APOH SNPs with sustained virological response and of ITPA SNPs with anemia related phenotypes by means of logistic regression assuming an additive genetic model.Results
None of the six APOH SNPs were associated with sustained virological response. The favorable alleles of the IL28B SNPs rs12979860 and rs368234815 were associated with sustained virological response (rs12979860: OR = 2.35[1.50–3.70], P = 2x10-4). Refined analysis showed that the effect of IL28B SNPs on sustained virological response was restricted to prior PegIFN/RBV relapse (OR = 3.80[1.82–8.92], P = 8x10-4). We also confirmed the association between ITPA low activity alleles and protection against early hemoglobin decline in triple therapy (P = 2x10-5).Conclusion
Our results suggest that the screening of rs12979860 may remain interesting for decision making in prior relapse HCV-1 Caucasian patients with compensated cirrhosis eligible for a telaprevir- or boceprevir-based therapy. 相似文献6.
Laurence Dutot Pascaline Lécorché Fabienne Burlina Rodrigue Marquant Vanessa Point Sandrine Sagan Gérard Chassaing Jean-Maurice Mallet Solange Lavielle 《Journal of chemical biology》2010,3(2):51-65
Cell-penetrating peptides (CPPs), which are usually short basic peptides, are able to cross cell membranes and convey bioactive
cargoes inside cells. CPPs have been widely used to deliver inside cells peptides, proteins, and oligonucleotides; however,
their entry mechanisms still remain controversial. A major problem concerning CPPs remains their lack of selectivity to target
a specific type of cell and/or an intracellular component. We have previously shown that myristoylation of one of these CPPs
affected the intracellular distribution of the cargo. We report here on the synthesis of glycosylated analogs of the cell-penetrating
peptide (R6/W3): Ac-RRWWRRWRR-NH2. One, two, or three galactose(s), with or without a spacer, were introduced into the sequence of this nonapeptide via a triazole link, the Huisgen reaction being achieved on a solid support. Four of these glycosylated CPPs were coupled via a disulfide bridge to the proapoptotic KLAK peptide, (KLAKLAKKLAKLAK), which alone does not enter into cells. The effect
on cell viability and the uptake efficiency of different glycosylated conjugates were studied on CHO cells and were compared
to those of the nonglycosylated conjugates: (R6/W3)S-S-KLAK and penetratinS-S-KLAK. We show that glycosylation significantly
increases the cell viability of CHO cells compared to the nonglycosylated conjugates and concomitantly decreases the internalization
of the KLAK cargo. These results suggest that glycosylation of CPP may be a key point in targeting specific cells. 相似文献
7.
Gaildrat P Møller M Mukda S Humphries A Carter DA Ganapathy V Klein DC 《The Journal of biological chemistry》2005,280(17):16851-16860
The oligopeptide transporter 1, PepT1, is a member of the Slc15 family of 12 membrane-spanning domain transporters; PepT1 has proton/peptide cotransport activity and is selectively expressed in intestinal epithelial cells, where it is responsible for the nutritional absorption of di- and tri-peptides. Here, a novel PepT1 gene product has been identified in the rat pineal gland, termed pgPepT1. It encodes a 150-amino acid protein encompassing the C-terminal 3 membrane-spanning domains of intestinal PepT1 protein, with 3 additional N-terminal residues. Expression of pgPepT1 appears to be restricted to the pineal gland and follows a marked circadian pattern with >100-fold higher levels of mRNA occurring at night; this is accompanied by an accumulation of membrane-associated pgPepT1 protein ( approximately 16 kDa). The daily rhythm in pgPepT1 mRNA is regulated by the well described neural pathway that controls pineal melatonin production. This includes the retina, the circadian clock in the suprachiasmatic nucleus, central structures, and projections from the superior cervical ganglia; activation of this pathway results in the release of norepinephrine. Here it was found that pgPepT1 expression is mediated by a norepinephrine-->cyclic AMP mechanism that activates an alternative promoter located in intron 20 of the gene. pgPepT1 protein was found to have transporter-modulator activity; it could contribute to circadian changes in pineal function through this mechanism. 相似文献
8.
A coumaroyl-ester-3-hydroxylase insertion mutant reveals the existence of nonredundant meta-hydroxylation pathways and essential roles for phenolic precursors in cell expansion and plant growth 总被引:6,自引:0,他引:6
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Abdulrazzak N Pollet B Ehlting J Larsen K Asnaghi C Ronseau S Proux C Erhardt M Seltzer V Renou JP Ullmann P Pauly M Lapierre C Werck-Reichhart D 《Plant physiology》2006,140(1):30-48
Cytochromes P450 monooxygenases from the CYP98 family catalyze the meta-hydroxylation step in the phenylpropanoid biosynthetic pathway. The ref8 Arabidopsis (Arabidopsis thaliana) mutant, with a point mutation in the CYP98A3 gene, was previously described to show developmental defects, changes in lignin composition, and lack of soluble sinapoyl esters. We isolated a T-DNA insertion mutant in CYP98A3 and show that this mutation leads to a more drastic inhibition of plant development and inhibition of cell growth. Similar to the ref8 mutant, the insertion mutant has reduced lignin content, with stem lignin essentially made of p-hydroxyphenyl units and trace amounts of guaiacyl and syringyl units. However, its roots display an ectopic lignification and a substantial proportion of guaiacyl and syringyl units, suggesting the occurrence of an alternative CYP98A3-independent meta-hydroxylation mechanism active mainly in the roots. Relative to the control, mutant plantlets produce very low amounts of sinapoyl esters, but accumulate flavonol glycosides. Reduced cell growth seems correlated with alterations in the abundance of cell wall polysaccharides, in particular decrease in crystalline cellulose, and profound modifications in gene expression and homeostasis reminiscent of a stress response. CYP98A3 thus constitutes a critical bottleneck in the phenylpropanoid pathway and in the synthesis of compounds controlling plant development. CYP98A3 cosuppressed lines show a gradation of developmental defects and changes in lignin content (40% reduction) and structure (prominent frequency of p-hydroxyphenyl units), but content in foliar sinapoyl esters is similar to the control. The purple coloration of their leaves is correlated to the accumulation of sinapoylated anthocyanins. 相似文献
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Mitochondrial dysfunction is a component of many neurodegenerative conditions. Measurement of oxygen consumption from intact neurons enables evaluation of mitochondrial bioenergetics under conditions that are more physiologically realistic compared to isolated mitochondria. However, mechanistic analysis of mitochondrial function in cells is complicated by changing energy demands and lack of substrate control. Here we describe a technique for sequentially measuring respiration from intact and saponin-permeabilized cortical neurons on single microplates. This technique allows control of substrates to individual electron transport chain complexes following permeabilization, as well as side-by-side comparisons to intact cells. To illustrate the utility of the technique, we demonstrate that inhibition of respiration by the drug KB-R7943 in intact neurons is relieved by delivery of the complex II substrate succinate, but not by complex I substrates, via acute saponin permeabilization. In contrast, methyl succinate, a putative cell permeable complex II substrate, failed to rescue respiration in intact neurons and was a poor complex II substrate in permeabilized cells. Sequential measurements of intact and permeabilized cell respiration should be particularly useful for evaluating indirect mitochondrial toxicity due to drugs or cellular signaling events which cannot be readily studied using isolated mitochondria. 相似文献
10.
Jean-Etienne Bassard Ludovic Richert Jan Geerinck Hugues Renault Frédéric Duval Pascaline Ullmann Martine Schmitt Etienne Meyer Jer?me Mutterer Wout Boerjan Geert De Jaeger Yves Mely Alain Goossens Danièle Werck-Reichhart 《The Plant cell》2012,24(11):4465-4482
Supramolecular organization of enzymes is proposed to orchestrate metabolic complexity and help channel intermediates in different pathways. Phenylpropanoid metabolism has to direct up to 30% of the carbon fixed by plants to the biosynthesis of lignin precursors. Effective coupling of the enzymes in the pathway thus seems to be required. Subcellular localization, mobility, protein–protein, and protein–membrane interactions of four consecutive enzymes around the main branch point leading to lignin precursors was investigated in leaf tissues of Nicotiana benthamiana and cells of Arabidopsis thaliana. CYP73A5 and CYP98A3, the two Arabidopsis cytochrome P450s (P450s) catalyzing para- and meta-hydroxylations of the phenolic ring of monolignols were found to colocalize in the endoplasmic reticulum (ER) and to form homo- and heteromers. They moved along with the fast remodeling plant ER, but their lateral diffusion on the ER surface was restricted, likely due to association with other ER proteins. The connecting soluble enzyme hydroxycinnamoyltransferase (HCT), was found partially associated with the ER. Both HCT and the 4-coumaroyl-CoA ligase relocalized closer to the membrane upon P450 expression. Fluorescence lifetime imaging microscopy supports P450 colocalization and interaction with the soluble proteins, enhanced by the expression of the partner proteins. Protein relocalization was further enhanced in tissues undergoing wound repair. CYP98A3 was the most effective in driving protein association. 相似文献