Open Innovation in the light of Patent Law.

The results of the individual chapters are summarized below, starting with chapter 2. The first chapter is the introduction. Finally, the main research question is answered. Chapter 2: Limitations and Definitions Definitions for CI and OI were developed from which the variants of the innovation methods were derived. Definitions of CI and OI: Closed Innovation (CI) CI is an innovation method for creating an innovation for an organization, wherein only internal inventors and only this organization is involved in the innovation method. Open Innovation (OI) OI is an innovation method for creating an innovation for an organization, wherein at least one step of the innovation method is outside this organization. Four variants of innovation methods were derived from the definitions of OI and CI, that have the following characteristics: Closed Innovation (CI) One organization and internal inventors Variant 1 of Open Innovation (OI with-an-external-inventor) One organization and at least one external inventor Variant 2 of Open Innovation (firm-to-firm OI (Hagedoorn and Zobel, 2015, p. 1050)) Two or more organizations and internal inventors Variant 3 of Open Innovation (firm-to-firm OI with-an-external-inventor) Two or more organizations and at least one external inventor Inventors are those participants in an innovation process who make a creative contribution in terms of patent law to the resulting innovation. Chapter 3: State of the Scientific Research Evaluation of the state of scientific research has shown that there are very few studies on the interaction between patent law and OI on the low-level of concrete provisions of the patent law. Chapter 4: Coexistence of OI and Patent Law In the scientific community, it has been argued that patent law and OI are contradictory concepts. It was stated that patent law would hinder or even prevent OI. Therefore, it was concluded that patent law should be abolished in order to fully exploit the benefits of the OI concept.(von Hippel and von Krogh, 2006; Wilson, 2009; Baldwin and von Hippel, 2011) Many interfaces between patent law and OI have been found to refute these conclusions. Instead, in some areas patent law even helps to implement the OI concept.(Murray and Stern, 2007; de Jong et al., 2008, pp. 39–40; Hagedoorn and Zobel, 2015) At least, it can be stated that patent law and OI are not fundamentally mutually exclusive. Chapter 5: Touchpoints between OI and Patent Law It has been pointed out that one link between patent law and an OI project is the interface between invention and innovation. The invention is assigned to the subject area of patent law and innovation is assigned to the subject area of OI.(Drucker, 1986, p. 62; Keukenschrijver, 2016b Rdn. 6-10; Moufang, 2017a Rdn. 15) An innovation can be created by an OI project. If this innovation fulfils the requirements of an invention, patent law is relevant. In this case, it can be checked whether the innovation of the OI project can lead to a patent.(Kraßer and Ann, 2016, §25) Furthermore, there are effects on the innovation by the innovation method used such as OI through the prohibition rights of patent law and the legal instrument of unlawful extraction.(Keukenschrijver, 2016o, 2016c, 2016n; Kraßer and Ann, 2016, §§31 and 32; Moufang, 2017n; Rinken, 2017f, 2017a) Therefore there are three points of contact between patent law and OI, namely because OI can result in inventions in terms of patent law, because of the prohibition rights of patent law and because of the legal instrument of unlawful removal. Chapter 6: Properties of an Invention The characteristics of an invention due to patent law were determined, wherein those characteristics, which have to be fulfilled that there is an invention at all, were disregarded. These characteristics must be fulfilled anyway, so that the patent law is relevant at all. An invention according to patent law has the following characteristics: • being in the right language (Schäfers, 2015e; Stauder, 2016a; Moufang, 2017e; Visser, 2017, pp. 18–25), • feasibility (Moufang, 2017c Rdn. 349-362), • susceptible of industrial applicability (Moufang, 2017j; Visser, 2017, pp. 126–127), • being a state secret (Schäfers, 2015i), • mentioning the inventor (Teschemacher, 2016b; Moufang, 2017f), • property in the invention (Keukenschrijver, 2016l; Moufang, 2017l), • novelty (Keukenschrijver, 2016g; Moufang, 2017b) and • inventive activity (Keukenschrijver, 2016j; Moufang, 2017g). Chapter 7: Relevant Properties of an Invention It was found that four properties of an invention are indeed influenced by the innovation method chosen, namely mention of the inventor, property in the invention, novelty and inventive activity. Therefore, these properties have an effect on the way patent law works with respect to the innovation method chosen. The effects of these properties are as follows: • Patent law requires that the inventors will be mentioned.(Teschemacher, 2016b; Moufang, 2017f) Therefore, the inventors must be identified. • In addition, the invention leads directly to a claim to ownership of the invention for the inventor.(Keukenschrijver, 2016l; Moufang, 2017l) Such a claim can, for example, stand in opposition to the wish of an initiator of a crowdsourcing project. Naturally, the initiator strives for ownership of an resulting invention of the crowdsourcing project.(Geschka and Meitinger, 2016) • Due to the open character of OI, there is a danger that an invention will become known and is therefore no longer new and inventive.(Keukenschrijver, 2016g, 2016j, Moufang, 2017b, 2017g) In this case, it is not possible to patent the invention.(Kraßer and Ann, 2016, §25) The following table 44 shows all possible properties of an invention, namely those which are a requirement for being an invention at all, all possible properties in terms of patent law and those properties, which have an effect on the way patent law is working depending on the innovation method chosen. Table 44 shows all properties of an invention. In the first column of the table (requirement of an invention), the properties that are a prerequisite for an invention are determined as "yes". These properties are used in section 5.3.3 of chapter 5 to determine whether an innovation by OI can be an invention under patent law at all. The second column (directing patent law) of the table 44 lists the characteristics of an invention with "yes" that influence the way patent law is working. For example, only a new and inventive invention can become a patent. These properties are determined in chapter 6. Inventorship comprises the characteristics of mention of the inventor and property of the invention. The third column determines those properties of an invention which not only control patent law but are additionally influenced by the type of innovation method chosen. These properties are determined in chapter 7. Chapter 8: Groups of Innovation Methods Four variants of innovation methods before the background of patent law were found, namely: • Closed innovation, • variant 1 of OI: OI with-an-external-inventor, • variant 2 of OI: firm-to-firm OI and • variant 3 of OI: firm-to-firm OI with-an-external-inventor. Closed Innovation (CI) is characterized by the fact that all steps of the innovation process are within one organization. An OI with-an-external-inventor (variant 1 of OI) is an innovation method that is characterized by the participation of at least one external inventor. This inventor is not a member of the organization. The variant 2 of OI is called a firm-to-firm OI (Hagedoorn and Zobel, 2015, p. 1050) which is an OI innovation method wherein at least two organizations, such as companies or universities, are involved in the development of the innovation. Further, all the inventors are internal inventors, which means that every inventor belongs to one of the companies involved in the innovation process. The variant 3 of OI is called a firm-to-firm OI with-an-external-inventor. This variant is characterized by the fact that it is a sequence of the variants 1 and 2 of OI. It does not matter which part of the sequence starts first and which part is succeeding. A grouping of the innovation methods has been carried out. From the viewpoint of patent law, CI and firm-to-firm OI constitute a first group and OI with-an- external-inventor and firm-to-firm OI with-an-external-inventor form a second group: • Group 1 (not critical with regard to patent law): o CI and o firm-to-firm OI • Group 2 (critical with regard to patent law): o OI with-an-external-inventor and o firm-to-firm OI with-an-external-inventor. CI and firm-to-firm OI are to be assessed as not critical before the background of patent law. On the other hand, OI with-an-external-inventor and firm-to-firm OI with-an-external-inventor are critical with regard to all four relevant properties of an invention. Therefore, the characteristic of "having at least one external inventor" means that an innovation method must be regarded as critical. If you add to CI an external inventor you get OI with-an-external-inventor. If you add to firm-to-firm OI an external inventor, you arrive at firm-to-firm OI with-an-external-inventor. CI and OI with-an-external-inventor as well as firm- to-firm OI and firm-to-firm OI with-an-external-inventor therefore represent contradictory pairings from the point of view of patent law, whereby the members of group 1 are uncritical and the innovation methods of group 2 are to be regarded as critical from the viewpoint of patent law. Chapter 9: OI and Prohibition Rights The variants of innovation methods have been categorised on the basis of the possibilities of having the innovations of the innovation methods granted as patents. This resulted in two groups, namely a group 1, which comprises CI and firm-to-firm OI, and as a second group OI with-an-external-inventor and firm- to-firm OI with-an-external-inventor. A further effect on the innovation methods and the resultant innovations may come from the prohibition rights under patent law. The prohibition rights enable a patent holder to prohibit the use of a protected invention.(Keukenschrijver, 2016o, 2016c, Rinken, 2017f, 2017a) The question arose whether a different grouping of the innovation methods results in the light of the prohibition rights due to patent law. However, it was found that the grouping of the innovation methods already determined is also relevant before the background of the prohibition rights. Chapter 10: OI and Unlawful Removal The grouping of innovation methods found was examined in the light of the legal instrument of unlawful removal due to patent law. An invention is deemed to have been withdrawn unlawfully if a person who is not entitled files a patent application for this invention with the patent office.(Keukenschrijver, 2016n; Moufang, 2017n) It was found that the same grouping as in the previous two chapters is valid before the background of the legal instrument of unlawful removal. Chapter 11: Empirical Studies It has been found that CI is dominant in innovations, which result in patent applications. Therefore the importance of OI for patents was questioned.(Meitinger, 2017b, 2017c) The empirical studies of the thesis have confirmed with a more comprehensive examination, that indeed OI, in comparison to CI, plays little role in patent applications. Therefore, at the moment it can be stated, that “Thus, there will likely remain a certain level of ´closed-ness´…”.(Keupp and Gassmann, 2009, p. 338) The empirical studies show that there are very few patent applications due to firm-to-firm OI, although firm-to-firm OI is compatible with patent law. However, it must be borne in mind that firm-to-firm OIs can be critical under antitrust law.(Besen and Slobodenjuk, 2011, pp. 300–301; Fuchs, 2012 Rdn. 2-9) It can therefore be assumed that at least some firm-to-firm OI innovation projects might be prevented due to concerns because of antitrust law. On the other hand, innovation methods with an external inventor lead to fewer patent applications compared to the corresponding innovation methods without an external inventor. This result was attributed to the fact that the corresponding innovations are not compatible with patent law. In principle, it would be conceivable that it is not the existence of the external inventor that is responsible for the filing or waiving of a patent application, but in particular the specificity of the organization concerned. For this reason, organizations carrying out innovation methods with external inventors were roughly compared with those organizations carrying out innovation methods without external inventors. No obvious differences in criteria such as company size, industrial sector, etc. were found. Summarizing the empirical studies, CI is dominant with respect to OI with-an- external-inventor and firm-to-firm OI dominates in comparison to firm-to-firm OI with-an-external-inventor. Further, the group 1 is dominant compared to group 2. Therefore, the theoretical findings of the thesis could not be falsified by the empirical studies. Chapter 12: Proposals to amend Patent Law Several suggestions have been developed in this thesis in order to better adapt patent law to OI. A change in the inventor's principle has been proposed to allow organizations to acquire ownership of an invention that they have initiated. Such an amendment is particularly advantageous with regard to OI with-an-external-inventor and firm-to-firm OI with-an-external-inventor, for example as crowdsourcing.(Meitinger, 2017d) A comparison was made between the employer-employee relationship and the relationship of a crowdsourcer to a crowd member. It has been found that there are similarities, suggesting that a similar law to the GEIA for the needs of crowdsourcing should be drawn up.(Meitinger, 2016) Such a special law would be also an adequate response by the legislature to the development of the labor market, with ever more flexible forms of work.(Deinert, 2014; Uffmann, 2016) The 18 months period of secrecy due to §32(2) sentence 1 PatG in conjunction with §31(2) No. 2 PatG prevents the search for current state-of-the-art documents.(Rudloff-Schäffer, 2017a Rdn. 33) This increases legal uncertainty about the patentability of inventions. In particular, inventions of OI projects are affected by this, as their open character increases the likelihood that similar patent applications will be filed. It was proposed to abolish this time period in order to be able to search the relevant prior art as early as possible. This would make it easier to ascertain whether an invention by an external inventor is patentable or whether it infringes third party intellectual property rights.(Meitinger, 2017a) Chapter 13: Miscellaneous Approaches There is an incentive theory as justification for patent law that says that the possibility of patenting an invention would spur technological development, which promotes the economy of the country concerned.(Rogge and Melullis, 2015 Rdn. 3; Keukenschrijver, 2016q Rdn. 68) However, patent law is evaluated by other scholars as disadvantageous because of macroeconomic concerns.(Mansfield, 1986, p. 180; Chu, 2009, p. 75; Lerner, 2009, p. 347) Therefore, patent law is seen controversial.(Encaoua and Hollander, 2002, p. 63; Shapiro, 2002, p. 70) The abolition of patent law was recommended. Alternatively, it is recommended a case law which favors OI, as OI is generally considered to be worthy of protection.(Wiebe, 2004; Boyle, 2006) However, this cannot be taken across the board, as OI is also used to monopolize markets. This can be done by the introduction of products to the markets being available for free. This ensures a high market penetration, wherein complements of these products are not accessible for free. These complements are needed for full functionality and will be made accessible only after sale.(West and Gallagher, 2006, pp. 325–327) For this reason, the jurisprudence should not be based on the assumption of consistently positive OI projects. A further possibility to improve harmonization of OI and patent law can result from the use of the technology of smart contracts. Smart contracts could manage innovations of OI projects in such a way, that their patentability is not infringed. Additionally an disadvantageous influence, which occurs through the prohibition rights of patent law or through the legal instrument of unlawful extraction could be prevented.(Meitinger, 2017f) In addition, a smart contract could design the ownership rights to an invention in such a way that they are more suitable for OI. Chapter 14: Recommendations for Users of OI Suggestions for OI users have been developed before the background of the current patent law. One suggestion is to document all contributions of the inventors with their date and origin. This makes it possible to meet the legal requirements of patent law after mention the inventors. In addition, it is recommended to enter into appropriate transfer agreements with each inventor so that ownership of the invention can be acquired.(Geschka and Meitinger, 2016, p. 33) It is recommendable to file the resulting invention with a patent office as early as possible. In this case, an early filing date protects against third party patents.(Keukenschrijver, 2016i Rdn. 3-4; Kraßer and Ann, 2016, §25 Rdn. 6; Teschemacher, 2016a Rdn. 1; Moufang, 2017d Rdn. 11-15).Administración y Dirección de Empresa

Reconfigurable Processing Units vs. Reconfigurable Interconnects

The question we proposed to explore with the seminar participants is whether the dynamic reconfigurable computing community is paying sufficient attention to the subject of dynamic reconfigurable SoC interconnects. By SoC interconnect, we refer to architecture- or system-level building blocks such as on-chip buses, crossbars, add-drop rings or meshed NoCs. P Our motivation to systematically investigate this question originates from conceptual and architectural challenges in the FlexPath project. FlexPath is a new Network Processor architecture that flexibly maps networking functions onto both SW programmable CPU resources and (re-)configurable HW building blocks in a way that different packet flows are forwarded via different, optimized processing paths. Packets with well defined processing requirements may even bypass the central CPU complex (AutoRoute). In consequence, CPU processing resources are more effectively used and the overall NP throughput is improved compared to conventional NPU architectures. P The following requirements apply with respect to the dynamic adaptation of the processing paths: The rule basis for NPU-internal processing path lookup is updated in the order of 100us, packet inter-arrival time is in the order of 100ns. Partial reconfiguration of the rule basis (and/or interconnect structure) with state of the art techniques would take several ms resulting in a continuously blocked system. However, performing path selection with conventional lookup table search and updates (and a statically configured on-chip bus) takes considerably less than 100ns. Hence, is there a need for new conceptual approaches with respect to dynamic SoC interconnect reconfiguration, or is this a \u27\u27no issue\u27\u27 as conventional techniques are sufficient

Procolipase gene : no association with early-onset obesity or fat intake

Copyright 2009 S. Karger AG, Basel.Peer reviewedPublisher PD

Whole genome sequencing of a single Bos taurus animal for single nucleotide polymorphism discovery

The next generation sequencing of a single cow genome with low-to-medium coverage has revealed 2.44 million new SNPs

Discovery of Sexual Dimorphisms in Metabolic and Genetic Biomarkers

Metabolomic profiling and the integration of whole-genome genetic association data has proven to be a powerful tool to comprehensively explore gene regulatory networks and to investigate the effects of genetic variation at the molecular level. Serum metabolite concentrations allow a direct readout of biological processes, and association of specific metabolomic signatures with complex diseases such as Alzheimer's disease and cardiovascular and metabolic disorders has been shown. There are well-known correlations between sex and the incidence, prevalence, age of onset, symptoms, and severity of a disease, as well as the reaction to drugs. However, most of the studies published so far did not consider the role of sexual dimorphism and did not analyse their data stratified by gender. This study investigated sex-specific differences of serum metabolite concentrations and their underlying genetic determination. For discovery and replication we used more than 3,300 independent individuals from KORA F3 and F4 with metabolite measurements of 131 metabolites, including amino acids, phosphatidylcholines, sphingomyelins, acylcarnitines, and C6-sugars. A linear regression approach revealed significant concentration differences between males and females for 102 out of 131 metabolites (p-values<3.8 x 10(-4); Bonferroni-corrected threshold). Sex-specific genome-wide association studies (GWAS) showed genome-wide significant differences in beta-estimates for SNPs in the CPS1 locus (carbamoyl-phosphate synthase 1, significance level: p<3.8 x 10(-10); Bonferroni-corrected threshold) for glycine. We showed that the metabolite profiles of males and females are significantly different and, furthermore, that specific genetic variants in metabolism-related genes depict sexual dimorphism. Our study provides new important insights into sex-specific differences of cell regulatory processes and underscores that studies should consider sex-specific effects in design and interpretation

Do common genetic variants in endotoxin signaling pathway contribute to predisposition to alcoholic liver cirrhosis?

Background: Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), produced by endotoxin-activated Kupffer cells, play a key role in the pathogenesis of alcoholic liver cirrhosis (ALC). Alleles TNFA -238A, IL1B -31T and variant IL1RN*2 of repeat polymorphism in the gene encoding the IL-1 receptor antagonist increase production of TNF-α and IL-1β, respectively. Alleles CD14 -159T, TLR4 c.896G and TLR4 c.1196T modify activation of Kupffer cells by endotoxin. We confirmed the published associations between these common variants and genetic predisposition to ALC by means of a large case-control association study conducted on two Central European populations. Methods: The study population comprised a Czech sample of 198 ALC patients and 370 controls (MONICA project), and a German sample of 173 ALC patients and 331 controls (KORA-Augsburg), and 109 heavy drinkers without liver disease. Results: Single locus analysis revealed no significant difference between patients and controls in all tested loci. Diplotype [IL1RN*2/*2; IL1B -31T+] was associated with increased risk of ALC in the pilot study, but not in the validation samples. Conclusions: Although cytokine mediated immune reactions play a role in the pathogenesis of ALC, hereditary susceptibility caused by variants in the corresponding genes is low in Central European populations. Clin Chem Lab Med 2009;47:398-40

DHTKD1 Mutations Cause 2-Aminoadipic and 2-Oxoadipic Aciduria

Abnormalities in metabolite profiles are valuable indicators of underlying pathologic conditions at the molecular level. However, their interpretation relies on detailed knowledge of the pathways, enzymes, and genes involved. Identification and characterization of their physiological function are therefore crucial for our understanding of human disease: they can provide guidance for therapeutic intervention and help us to identify suitable biomarkers for monitoring associated disorders. We studied two individuals with 2-aminoadipic and 2-oxoadipic aciduria, a metabolic condition that is still unresolved at the molecular level. This disorder has been associated with varying neurological symptoms. Exome sequencing of a single affected individual revealed compound heterozygosity for an initiating methionine mutation (c.1A>G) and a missense mutation (c.2185G>A [p.Gly729Arg]) in DHTKD1. This gene codes for dehydrogenase E1 and transketolase domain-containing protein 1, which is part of a 2-oxoglutarate-dehydrogenase-complex-like protein. Sequence analysis of a second individual identified the same missense mutation together with a nonsense mutation (c.1228C>T [p.Arg410∗]) in DHTKD1. Increased levels of 2-oxoadipate in individual-derived fibroblasts normalized upon lentiviral expression of the wild-type DHTKD1 mRNA. Moreover, investigation of L-lysine metabolism showed an accumulation of deuterium-labeled 2-oxoadipate only in noncomplemented cells, demonstrating that DHTKD1 codes for the enzyme mediating the last unresolved step in the L-lysine-degradation pathway. All together, our results establish mutations in DHTKD1 as a cause of human 2-aminoadipic and 2-oxoadipic aciduria via impaired turnover of decarboxylation 2-oxoadipate to glutaryl-CoA

Recent advances in the genetics of atrial fibrillation: from rare and common genetic variants to microRNA signaling

Besides traditional risk factors, atrial fibrillation (AF) also shares a strong genetic component. Here, we review the genetics of AF including monogenic forms of AF, heritability of AF, complex genetic risk of AF, and the role of microRNAs in AF pathophysiology. Thirtytwo mutations (17 genes) have been reported to cause familial AF. Mutations in cardiac ion channel genes or their subunits alter electrical properties and thereby lead to AF. Recently, also non-ion channel gene mutations have been identified to cause familial AF. Twin and community-based studies suggested AF to be heritable also on the population level. The AF risk in the offspring of an affected first-degree relative ranged between 2- to 5-fold, depending on the age of onset. Thereby, the risk of AF increases gradually the earlier the youngest relative of an AF patient developed the arrhythmia. African Americans bear a lesser risk of AF compared to individuals of European ancestry. Their risk rises with increasing European admixture. Genome wide association studies have revealed loci on chromosomes 4q25, 16q21 and 1q21 conferring risk of AF. Very recently, another consortial effort has identified a novel locus on chromosome 1, intronic to IL6R. IL6R encodes the a subunit of the interleukin 6 receptor. MicroRNAs were shown to regulate gene expression, and are increasingly reported to modify AF. A hallmark of AF pathophysiology is electrical and structural remodeling. MicroRNAs are involved in this process by regulating gene expression of cardiac ion channels, calcium handling proteins, transcription factors, and extracellular matrix related proteins

Mutation screen and association studies in the Diacylglycerol O-acyltransferase homolog 2 gene (DGAT2), a positional candidate gene for early onset obesity on chromosome 11q13

<p>Abstract</p> <p>Background</p> <p><it>DGAT2 </it>is a promising candidate gene for obesity because of its function as a key enzyme in fat metabolism and because of its localization on chromosome 11q13, a linkage region for extreme early onset obesity detected in our sample.</p> <p>We performed a mutation screen in 93 extremely obese children and adolescents and 94 healthy underweight controls. Association studies were performed in samples of up to 361 extremely obese children and adolescents and 445 healthy underweight and normal weight controls. Additionally, we tested for linkage and performed family based association studies at four common variants in the 165 families of our initial genome scan.</p> <p>Results</p> <p>The mutation screen revealed 15 DNA variants, four of which were coding non-synonymous exchanges: p.Val82Ala, p.Arg297Gln, p.Gly318Ser and p.Leu385Val. Ten variants were synonymous: c.-9447A > G, c.-584C > G, c.-140C > T, c.-30C > T, IVS2-3C > G, c.812A > G, c.920T > C, IVS7+23C > T, IVS7+73C > T and *22C > T. Additionally, the small biallelic trinucleotide repeat rs3841596 was identified. None of the case control and family based association studies showed an association of investigated variants or haplotypes in the genomic region of <it>DGAT2</it>.</p> <p>Conclusion</p> <p>In conclusion, our results do not support the hypothesis of an important role of common genetic variation in <it>DGAT2 </it>for the development of obesity in our sample. Anyhow, if there is an influence of genetic variation in <it>DGAT2 </it>on body weight regulation, it might either be conferred by the less common variants (MAF < 0.1) or the detected, rare non-synonymous variants.</p

Mutations of the Mitochondrial-tRNA Modifier MTO1 Cause Hypertrophic Cardiomyopathy and Lactic Acidosis

Dysfunction of mitochondrial respiration is an increasingly recognized cause of isolated hypertrophic cardiomyopathy. To gain insight into the genetic origin of this condition, we used next-generation exome sequencing to identify mutations in MTO1, which encodes mitochondrial translation optimization 1. Two affected siblings carried a maternal c.1858dup (p.Arg620Lysfs∗8) frameshift and a paternal c.1282G>A (p.Ala428Thr) missense mutation. A third unrelated individual was homozygous for the latter change. In both humans and yeast, MTO1 increases the accuracy and efficiency of mtDNA translation by catalyzing the 5-carboxymethylaminomethylation of the wobble uridine base in three mitochondrial tRNAs (mt-tRNAs). Accordingly, mutant muscle and fibroblasts showed variably combined reduction in mtDNA-dependent respiratory chain activities. Reduced respiration in mutant cells was corrected by expressing a wild-type MTO1 cDNA. Conversely, defective respiration of a yeast mto1Δ strain failed to be corrected by an Mto1Pro622∗ variant, equivalent to human MTO1Arg620Lysfs∗8, whereas incomplete correction was achieved by an Mto1Ala431Thr variant, corresponding to human MTO1Ala428Thr. The respiratory yeast phenotype was dramatically worsened in stress conditions and in the presence of a paromomycin-resistant (PR) mitochondrial rRNA mutation. Lastly, in vivo mtDNA translation was impaired in the mutant yeast strains