ABSTRACT
This study presents the first 10-year follow-up investigation of the implant survival and peri-implant outcomes of one-piece mini dental implants (MDIs) retaining mandibular implant overdentures (IODs), including marginal bone level alterations (ΔMBLs), clinical peri-implant parameters, and complications. Twenty participants with horizontally atrophied mandibles received complete dentures and four MDIs (diameter 1.8 mm) at baseline. The dentures were converted into IODs with O-ring attachments. The 10-year follow-up comprised a radiological assessment of ΔMBLs, peri-implant parameters, as well as biological and technical complications. Results from a 10-year follow-up of 14 participants showed a 100% implant survival rate for all 56 implants. The mean ΔMBL after 10 years was -1.12 ± 0.80 mm, with 49 implants classified as successful (ΔMBL < 2 mm) and 7 implants with satisfactory survival (ΔMBL 2-4 mm). Time after implant placement significantly influenced ΔMBL, with stable MBLs after 5 years. The prosthetic survival rate after 10 years was 93%. ΔMBLs were not influenced by implant position or gender but were significantly smaller in subjects older than 65 years. Conclusively, one-piece MDIs with O-ring attachments offer a reliable treatment option for horizontally atrophied mandibles after 10 years, with high implant and prosthetic survival rates, potentially benefiting from advanced age regarding peri-implant bone stability.
ABSTRACT
BACKGROUND: Nitric oxide synthase 1 adaptor protein (NOS1AP; previously named CAPON) is linked to the glutamatergic postsynaptic density through interaction with neuronal nitric oxide synthase (nNOS). NOS1AP and its interaction with nNOS have been associated with several mental disorders. Despite the high levels of NOS1AP expression in the hippocampus and the relevance of this brain region in glutamatergic signalling as well as mental disorders, a potential role of hippocampal NOS1AP in the pathophysiology of these disorders has not been investigated yet. METHODS: To uncover the function of NOS1AP in hippocampus, we made use of recombinant adeno-associated viruses to overexpress murine full-length NOS1AP or the NOS1AP carboxyterminus in the hippocampus of mice. We investigated these mice for changes in gene expression, neuronal morphology, and relevant behavioural phenotypes. FINDINGS: We found that hippocampal overexpression of NOS1AP markedly increased the interaction of nNOS with PSD-95, reduced dendritic spine density, and changed dendritic spine morphology at CA1 synapses. At the behavioural level, we observed an impairment in social memory and decreased spatial working memory capacity. INTERPRETATION: Our data provide a mechanistic explanation for a highly selective and specific contribution of hippocampal NOS1AP and its interaction with the glutamatergic postsynaptic density to cross-disorder pathophysiology. Our findings allude to therapeutic relevance due to the druggability of this molecule. FUNDING: This study was funded in part by the DFG, the BMBF, the Academy of Finland, the NIH, the Japanese Society of Clinical Neuropsychopharmacology, the Ministry of Education of the Russian Federation, and the European Community.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Endophenotypes , Gene Expression , Hippocampus/metabolism , Mental Disorders/etiology , Mental Disorders/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Animals , Biomarkers , Disease Models, Animal , Disease Susceptibility , Disks Large Homolog 4 Protein/metabolism , Gene Expression Regulation , Hippocampus/physiopathology , Male , Mental Disorders/diagnosis , Mice , Nitric Oxide Synthase Type I/metabolism , Protein Binding , Signal TransductionABSTRACT
One important reaction of chlorophyll (chl) breakdown during plant senescence is the removal of the lipophilic phytol moiety by chlorophyllase. AtCLH1 and AtCLH2 were considered to be required for this reaction in Arabidopsis thaliana. Here we present evidence against this assumption. Using green fluorescent protein fusions, neither AtCLH isoform localizes to chloroplasts, the predicted site of chlorophyll breakdown. Furthermore, clh1 and clh2 single and double knockout lines are still able to degrade chlorophyll during senescence. From our data we conclude that AtCLHs are not required for senescence-related chlorophyll breakdown in vivo and propose that genuine chlorophyllase has not yet been molecularly identified.
Subject(s)
Arabidopsis/growth & development , Arabidopsis/metabolism , Chlorophyll/metabolism , Apoptosis Regulatory Proteins/metabolism , Arabidopsis/genetics , Arabidopsis Proteins/metabolism , Carboxylic Ester Hydrolases/genetics , Carboxylic Ester Hydrolases/metabolism , Catalysis , Chloroplasts/metabolism , DNA, Plant/genetics , DNA, Plant/isolation & purification , Darkness , Isoenzymes/genetics , Isoenzymes/metabolism , Mutation/genetics , Oxidoreductases/metabolism , Oxygenases/metabolism , Plant Leaves/genetics , Plant Leaves/growth & development , Plant Leaves/metabolism , Plants, Genetically ModifiedABSTRACT
A central reaction of chlorophyll breakdown, porphyrin ring opening of pheophorbide a to the primary fluorescent chlorophyll catabolite (pFCC), requires pheophorbide a oxygenase (PAO) and red chlorophyll catabolite reductase (RCCR), with red chlorophyll catabolite (RCC) as a presumably PAO-bound intermediate. In subsequent steps, pFCC is converted to different fluorescent chlorophyll catabolites (FCCs) and nonfluorescent chlorophyll catabolites (NCCs). Here, we show that RCCR-deficient Arabidopsis thaliana accumulates RCC and three RCC-like pigments during senescence, as well as FCCs and NCCs. We also show that the stereospecificity of Arabidopsis RCCR is defined by a small protein domain and can be reversed by a single Phe-to-Val exchange. Exploiting this feature, we prove the in vivo participation of RCCR in chlorophyll breakdown. After complementation of RCCR mutants with RCCRs exhibiting alternative specificities, patterns of chlorophyll catabolites followed the specificity of complementing RCCRs. Light-dependent leaf cell death observed in different RCCR-deficient lines strictly correlated with the accumulation of RCCs and the release of singlet oxygen, and PAO induction preceded lesion formation. These findings suggest that RCCR absence causes leaf cell death as a result of the accumulation of photodynamic RCC. We conclude that RCCR (together with PAO) is required for the detoxification of chlorophyll catabolites and discuss the biochemical role(s) for this enzyme.