La neurotoxine β-N-méthyl-amino-l-alanine (BMAA) et ses isomères, notamment la N-(2- aminoéthyl glycine) (AEG), la β-amino-N-méthyl alanine (BAMA) et l'acide 2,4- diaminobutyrique (DAB), ont été détectés précédemment dans des échantillons de cyanobactéries. Cependant, il existe des rapports contradictoires concernant leur présence dans les eaux de surface. Dans cette étude, nous avons évalué l'impact de l'acide trichloracétique (TCA 0,1M) sur la détection des isomères de BMAA, par rapport aux protocoles préexistants. Une méthode instrumentale sensible a été utilisée pour l'étude, avec des limites de détection de l'ordre de 5-10 ng L-1. Des meilleures limites de détection plus élevés et des niveaux significativement plus importants (test des rangs signés de Wilcoxon appariés, p < 0,001) d'isomères de BMAA ont été observés dans les échantillons traités par le TCA, avec des augmentations relatives allant jusqu'à +725 % pour l'AEG et +1450 % pour le DAB, et des augmentations de concentration absolue allant jusqu'à +15 000 ng L-1 pour l'AEG et +650 ng L-1 pour le DAB. Nous avons également documenté les tendances de la présence des isomères de BMAA dans plusieurs lacs de différents pays tels que le Brésil, le Canada, la France, le Mexique et le Royaume-Uni. Les données obtenues au cours de cette étude (n = 390 provenant de 45 sites d'échantillonnage) indiquent des détections fréquentes des isomères AEG et DAB, avec des taux de détection de 30 % et 43 % et des niveaux maximums de 19 000 ng L-1 et 1 100 ng L-1, respectivement. En revanche, le BAMA a été trouvé dans moins de 8 % des échantillons d'eau, et la BMAA n'a été trouvée dans aucun échantillon. Ces résultats appuient les analyses des cyanobactéries libres, dans lesquelles la BMAA a souvent été détectée avec des concentrations inférieures de 2 à 4 ordres de grandeur à celles de l'AEG et du DAB. Les mesures saisonnières effectuées dans deux lacs impactés par des efflorescences ont indiqué des corrélations limitées entre les isomères de la BMAA et les microcystines totales ou la chlorophylle-a, ce qui mériterait une étude plus approfondie. / The neurotoxic alkaloid β-N-methyl-amino-l-alanine (BMAA) and related isomers, including N-(2-aminoethyl glycine) (AEG), β-amino-N-methyl alanine (BAMA) and 2,4-diaminobutyric acid (DAB), have been reported previously in cyanobacterial samples. However, there are conflicting reports regarding their occurrence in surface waters. In this study, we evaluated the impact of amending lake water samples with trichloroacetic acid (0.1M TCA) on the detection of BMAA isomers, compared with pre-existing protocols. A sensitive instrumental method was enlisted for the survey, with limits of detection in the range of 5-10 ng L-1. Higher detection limits ans significantly greater levels (paired Wilcoxon’s signed-rank tests, p < 0.001) of BMAA isomers were observed TCA-amended samples (method B) compared to samples without TCA (method A). The overall range of B/A ratios was 0.67-8.25 for AEG (up to +725 %) and 0.69-15.5 for DAB (up to +1450 %), with absolute concentration increases TCA-amended samples up to +15,000 ng L-1 for AEG and +650 ng L-1 for DAB. We also documented the trends in the occurrence of BMAA isomers for a large breadth of field-collected lakes from Brazil, Canada, France, Mexico, and the United Kingdom. Data gathered during this overarching campaign (overall n = 390 within 45 lake sampling sites) indicate frequent detections of AEG and DAB isomers, with detection rates of 30 % and 43 % and maximum levels of 19,000 ng L-1 and 1,100 ng L- 1, respectively. In contrast, BAMA was found in less than 8 % of the water samples, and BMAA not found in any sample. These results support analyses of free-living cyanobacteria, wherein BMAA was often reported at concentrations 2-4 orders of magnitude lower than AEG and DAB. Seasonal measurements conducted at two bloom-impacted lakes indicated limited correlations of BMAA isomers with total microcystins or chlorophyll-a, which deserves further investigation.

The supply of precursors from primary metabolism is often overlooked when engineering secondary metabolism for increased product yields. This is because precursor supply may be assumed to be non-limiting, and it is considered difficult to engineer primary metabolism, because control of carbon flow (flux) is generally distributed among most enzymes of the pathway. The aim of this thesis was to increase the production of sterols, part of the isoprenoid class of secondary metabolites, in tobacco (Nicotiana tabacum) Bright Yellow 2 (BY-2) cell cultures. This was achieved by genetically engineering increased activity of mitochondrial citrate synthase, an enzyme of the tricarboxylic acid (TCA) cycle that is involved in the provision of cytosolic acetyl coenzyme A, the primary metabolite precursor to sterols. Metabolic flux analysis revealed that citrate synthase exerts significant control over cyclic TCA cycle flux in BY-2 cells and suggested that increasing the activity of downstream enzymes within secondary metabolism could lead to a further redirection of TCA-cycle-derived precursors into sterol biosynthesis. Attempts were made to achieve this by genetically engineering increased activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), a key enzyme of secondary metabolism involved in sterol biosynthesis. Consistent with previous research, transgenic lines had increased sterol levels. However, the high sterol phenotype was unstable, and attempts to co-express HMGR and citrate synthase genes were unsuccessful. The thesis demonstrates that increasing the provision of precursors to secondary metabolites can result in increased yields of those secondary metabolites but suggests that in most cases the activity of enzymes within secondary metabolism has a greater effect on those yields. It also reveals that single enzymes can exert significant control of flux within primary metabolism, although the control exerted by specific enzymes probably changes with the demands placed on metabolism.

Ce mémoire illustre l'évolution de la stratégie du syndicat des TCA-Québec, unité locale 728 représentant les employés de l'usine Kenworth de Sainte-Thérèse, de la fermeture de l'usine en 1996 jusqu'à sa réouverture en 1999. La littérature démontre que la mondialisation des marchés économiques oblige les syndicats à revoir leur stratégie lors de négociations collectives. Parfois, leur survie en dépend. Les résultats de notre étude de cas permettent de déterminer cinq événements clés où le syndicat local revoit sa stratégie pendant ce conflit de travail médiatisé : la négociation collective, l'échec de la négociation menant à une grève générale, la fermeture de l'usine, l'annonce de la réouverture de l'usine ainsi que sa réouverture. L'ensemble des résultats présentés en corrélation avec le modèle d’analyse de David Weil (1994) présente la planification stratégique de ces cinq événements à partir d’un processus intégré qui peut être décomposé en trois principales étapes : la formulation de la stratégie, sa mise en œuvre et son évaluation. Les faits sont colligés chronologiquement en exposant les transformations de la stratégie du syndicat local par l'identification d'indicateurs conçus à partir des facteurs externes évoqués dans le modèle de Weil (1994), à savoir l'analyse de l'environnement technologique, législatif et social, les priorités dictées par les membres, l'allocation des ressources du syndicat, ainsi que l'analyse de l'évaluation avantage coûts versus bénéfices. / This thesis illustrates the evolution of the strategy used by the TCA-Québec Union, local unit 728 representing the employees of Kenworth in Sainte-Thérèse, from the plant shutdown in 1996 to its reopening in 1999. The literature shows that the economic market globalisation has forced the trade unions to reconsider their strategic approach in the collective bargaining process. In some cases, their survival depends on it. The case study presented in this work identifies five key events when strategic adjustments were made by the trade union during this highly mediatised conflict: the collective bargaining, the failure of these negotiations which led to a general strike, the plant shutdown, the announcement of the plant’s reopening as well as its actual reopening. The results presented in correlation to the David Weil Model (1994) detail the strategic planning of these five key events using an integrated process which is composed of three major steps: formulating, implementing and evaluating the strategy. The facts are assembled chronologically while exposing the modifications to the local union`s strategy using indicators developed with Weil’s model external factors (1994) such as the technological, legal and social environments, the member-led priorities, the distribution of the union’s resources as well as the cost-benefit advantages.

140 Abstract GOALS: Intention of my diessertation work was to answer the main research question: "What is the utilazation rate of TCA when working with involuntary clients of social workers from CPS in the capital city of Prague and selected CPS in Vysocina region?". Theoretical starting-points: Basic signs of TCA are partnerships and strenghten. In terms of TCA the success depends on How people can actively participate and understand the process of helping. Clients role is active and he is participating everything what has been happening in the whole process of helping. Task centered approach says, that experience from your own decision is more usefull then just assuming how the future situation could be. TCA holds the idea, which just a little success build up self-confidence and self-esteem. Accomplishing of goals and achieving of another goal motivates a client. When smaller goals are set up there is a much more chance for possitive result of the whole advisory process. METHODS: Semistructured questionnaire has been used. The questionnaire have 47 questions, which are based on operationalization of main research question. RESULTS: The outcome of questionnaire investigation method is that the workers don`t use TCA, but in general in their practice we are able to identify some of the elements of approach.

Die phytotoxisch wirkende Trichloressigsäure (TCA) wurde bis in die 1980er Jahre in Form von Natriumtrichloracetat (TCAA- Na) als Herbizid in der Land- und Forstwirtschaft eingesetzt. Mittlerweile ist die Verwendung von TCA als Herbizid aufgrund unerwünschter Nebenwirkungen auf Nutzpflanzen in den meisten europäischen Ländern und vielen weiteren Staaten der Erde untersagt. Tetrachlorethen (PER) gehört zur Stoffgruppe der leichtflüchtigen Chlorkohlenwasserstoffe (LCKW) und findet weltweit hauptsächlich als Entfettungs- und Reinigungsmittel in der metallverarbeitenden sowie chemischen Industrie Anwendung. Darüber hinaus kommen Altlasten, wie z.B. die im Landkreis Bitterfeld (Sachsen- Anhalt) gelegene Deponie Grube Antonie als anthropogene Flächenquelle von PER- Emissionen in Betracht. Die Grube Antonie verfügt über ein sehr großes Inventar sowohl an LCKW als auch an TCA und ist u.a. von Pioniergehölzen, wie der Birke (Betula pendula ROTH), besiedelt. PER wird unter bestimmten physikochemischen Bedingungen in der Atmosphäre zu TCA abgebaut. Darüber hinaus ist mittlerweile bekannt, daß PER nach stomatärer bzw. cuticulärer Resorption in der Blatt- bzw. Nadelmatrix von Pflanzen in Anwesenheit von reaktiven Sauerstoffspezies (ROS) u.a. zu phytotoxischer TCA metabolisiert werden kann. Aufgrund dieser biogenen TCA- Bildung wird PER auch in Verbindung mit neuartigen Waldschäden gebracht. Sowohl regionale als auch weltweit durchgeführte Untersuchungen zeigten, daß besonders Nadelgehölze, wie die Kiefer (Pinus sylvestris L.) z.T. hohe TCA- Gehalte in den Nadeln akkumulieren. Während in den letzten Jahren der Kenntnisstand hinsichtlich der natürlichen und anthropogenen TCA- Quellen immer mehr zunahm, ist über die schädigende Wirkung von TCA sowie ihrer Präcursoren (wie z.B. PER) auf Wild- und Forstpflanzen bisher nur wenig bekannt. Das Ziel der vorliegenden Arbeit bestand darin, anhand von ökotoxikologischen Untersuchungen sowie pflanzenphysiologischen (Chl a - Fluoreszenz), dendrologischen und biochemischen Meßmethoden zu prüfen, ob von Tetrachlorethen (PER) und dessen Metabolit Trichloressigsäure (TCA) ein phytototoxisches Risiko, insbesondere für die Baumarten Kiefer (Pinus sylvestris L.) und Birke (Betula pendula ROTH), ausgeht. Zur Erfüllung der Zielstellung wurden Monitoringuntersuchungen an PER/TCA- belasteten Birken, Untersuchungen zur Aufnahme, Akkumulation und Wirkung von über den Boden/Wurzel- Pfad appliziertem TCAA bei Kiefer sowie mehrjährige Untersuchungen zur PER- Applikation über den Luftpfad in Expositionskammern, zur Bildung und Akkumulation von TCA und zu PER/TCA- induzierten Wirkungen an Birken und Kiefern durchgeführt.

Sink limitations in plants reduce the potential for photosynthesis and yield, particularly under conditions that favour enhanced source activity such as elevated CO2 (EC). Dark respiration, considered catabolic, has rarely been exploited to enhance sink activity in plants. Arabidopsis thaliana L. lines with partially-suppressed mitochondrial pyruvate dehydrogenase (mtPDH) kinase (mtPDHK), a negative post-translational regulator of the mtPDH complex, was shown previously to have both elevated mtPDH complex activity and increased seed weight and oil content at ambient CO2 (AC), suggesting an enhancement of sink activity. The mtPDH links glycolysis with the tricarboxylic acid (TCA) cycle. It was hypothesized that Arabidopsis having suppressed mtPDHK will display their greatest plant productivity at EC through a combined enhancement of source and sink activities. Control and transgenic Arabidopsis having either constitutive or seed-specific expression of antisense mtPDHK were grown at either AC or EC. Expression of mtPDHK and mtPDH complex activity in rosette leaves and reproductive tissues were measured, which required the development of an assay to quantify mtPDH activity. Vegetative and reproductive growth over time, seed oil parameters, and leaf net C exchange were also quantified. A parabolic relationship was found between mtPDHK expression and mtPDH activity, reflecting a role for mtPDH in balancing photosynthetic and respiratory processes. A number of growth and seed oil parameters were improved in transgenic lines, particularly at EC; many of these parameters showed a significant linear or quadratic correlation with mtPDHK expression and mtPDH activity. The proportion of very long chain fatty acids was increased in transgenic lines. Leaf net C exchange was enhanced at AC and EC, and particularly in lines showing repression of mtPDHK. The greatest enhancement in total seed and oil productivity was found for the constitutive lines 104 and 31 at EC (up to 2.8 times). These two lines exhibited a significant increase in inflorescence size, an increase in leaf water use efficiency, the lowest rate of mtPDH complex inactivation by ATP, and an intermediary enhancement of mtPDH complex activity in seeds. Thus, it is concluded that the mtPDH plays a key role in regulating sink and source activities in plants. / Natural Sciences and Engineering Research Council (NSERC) through the Green Crop Networks Research Network; Ontario Graduate Scholarship; Syngenta Graduate Scholarship; Ball Farm Services and Agrico Canada Ltd. Scholarship; Mrs. Fred Ball Scholarship; Arthur D. Latornell Scholarship; Hoskins Scholarship; Robb Travel Grant; Registrars and the Deans Scholarship and travel awards and bursaries from the University of Guelph, and the Ontario Agricultural College.

Die phytotoxisch wirkende Trichloressigsäure (TCA) wurde bis in die 1980er Jahre in Form von Natriumtrichloracetat (TCAA- Na) als Herbizid in der Land- und Forstwirtschaft eingesetzt. Mittlerweile ist die Verwendung von TCA als Herbizid aufgrund unerwünschter Nebenwirkungen auf Nutzpflanzen in den meisten europäischen Ländern und vielen weiteren Staaten der Erde untersagt. Tetrachlorethen (PER) gehört zur Stoffgruppe der leichtflüchtigen Chlorkohlenwasserstoffe (LCKW) und findet weltweit hauptsächlich als Entfettungs- und Reinigungsmittel in der metallverarbeitenden sowie chemischen Industrie Anwendung. Darüber hinaus kommen Altlasten, wie z.B. die im Landkreis Bitterfeld (Sachsen- Anhalt) gelegene Deponie Grube Antonie als anthropogene Flächenquelle von PER- Emissionen in Betracht. Die Grube Antonie verfügt über ein sehr großes Inventar sowohl an LCKW als auch an TCA und ist u.a. von Pioniergehölzen, wie der Birke (Betula pendula ROTH), besiedelt. PER wird unter bestimmten physikochemischen Bedingungen in der Atmosphäre zu TCA abgebaut. Darüber hinaus ist mittlerweile bekannt, daß PER nach stomatärer bzw. cuticulärer Resorption in der Blatt- bzw. Nadelmatrix von Pflanzen in Anwesenheit von reaktiven Sauerstoffspezies (ROS) u.a. zu phytotoxischer TCA metabolisiert werden kann. Aufgrund dieser biogenen TCA- Bildung wird PER auch in Verbindung mit neuartigen Waldschäden gebracht. Sowohl regionale als auch weltweit durchgeführte Untersuchungen zeigten, daß besonders Nadelgehölze, wie die Kiefer (Pinus sylvestris L.) z.T. hohe TCA- Gehalte in den Nadeln akkumulieren. Während in den letzten Jahren der Kenntnisstand hinsichtlich der natürlichen und anthropogenen TCA- Quellen immer mehr zunahm, ist über die schädigende Wirkung von TCA sowie ihrer Präcursoren (wie z.B. PER) auf Wild- und Forstpflanzen bisher nur wenig bekannt. Das Ziel der vorliegenden Arbeit bestand darin, anhand von ökotoxikologischen Untersuchungen sowie pflanzenphysiologischen (Chl a - Fluoreszenz), dendrologischen und biochemischen Meßmethoden zu prüfen, ob von Tetrachlorethen (PER) und dessen Metabolit Trichloressigsäure (TCA) ein phytototoxisches Risiko, insbesondere für die Baumarten Kiefer (Pinus sylvestris L.) und Birke (Betula pendula ROTH), ausgeht. Zur Erfüllung der Zielstellung wurden Monitoringuntersuchungen an PER/TCA- belasteten Birken, Untersuchungen zur Aufnahme, Akkumulation und Wirkung von über den Boden/Wurzel- Pfad appliziertem TCAA bei Kiefer sowie mehrjährige Untersuchungen zur PER- Applikation über den Luftpfad in Expositionskammern, zur Bildung und Akkumulation von TCA und zu PER/TCA- induzierten Wirkungen an Birken und Kiefern durchgeführt.

Irritable bowel syndrome (IBS) is a functional disorder that affects the gastrointestinal tract and especially the large intestine. The pathogenesis of the disease is not fully understood, for that reason there is still no cure and current therapy focuses on symptom relief. The disease manifests itself in the form of abdominal pain, bloating, constipation or diarrhoea. New studies have shown a link between IBS and communication between the central nervous system and the gut. Serotonin and norepinephrine seem to be important for the course of the disease. The purpose of this literature review was to study the efficacy and safety of certain antidepressant preparations belonging to tricyclic antidepressants and selective serotonin reuptake inhibitors in the treatment of IBS. This work focused on the effect of preparations and how tolerable they are with respect to their side effects. Articles presented in this work were found in the PubMed database with the keywords "irritable bowel syndrome", "serotonin reuptake inhibitor", " tricyclic antidepressants ". Amitriptyline 10 mg and imipramine 25 mg provided a statistically significant symptom relief in IBS with diarrhoea (IBS-D) compared to placebo. In addition, tianeptine 12.5 mg 3 times / day, which belongs to the selective serotonin reuptake enhancer (SSRE) group, gave a corresponding symptom relief as amitriptyline 10 mg once / day. The difference between the two was not statistically significant, but the study was open label and non-placebo-controlled, which made it difficult to draw any conclusions. Fluoxetine, which belongs to the selective serotonin reuptake inhibitor (SSRI) group, produced a statistically significant effect compared to placebo in the treatment of constipation IBS (IBS-C). In contrast, paroxetine-CR did not have any statistically significant effect on abdominal pain in IBS-C compared with placebo. However, more patients in the paroxetine group achieved the secondary outcome (clinical global improvement) with scores of 1-2 on the scale Clinical Global Impressions-Improvement (CGI-I). Based on the studies presented in this literature study, it is concluded that a low dose of TCA is an effective and safe treatment for IBS-D while SSRIs are effective and safe in the treatment of IBS-C compared to placebo. / Irritable bowel syndrome (IBS), är funktionella störningar som drabbar gastrointestinalkanalen och framför allt kolon. Patogenesen till sjukdomen är inte helt klarlagd, av den anledningen saknas fortfarande någon botande behandling och dagens terapi fokuserar på symtomlindring. Sjukdomen yttrar sig i form av buksmärta, uppblåsthet, förstoppning eller diarré. Senaste studier har visat en koppling mellan IBS och kommunikation mellan centrala nervsystemet och tarmen. Serotonin och noradrenalin verkar ha betydelse för sjukdomsförlopp. Syftet med detta litteraturarbete var att studera effektivitet och säkerhet för några antidepressiva preparat som tillhör tricykliska antidepressiva och selektiva serotonin återupptagshämmare vid behandling av IBS. Detta arbete fokuserade på effekten av preparaten och hur tolererbara de är med avseende på deras biverkningar. Artiklar som presenteras i detta arbete söktes i databasen Pubmed med sökord ”irritable bowel syndrome”, ”serotonin reuptake inhibitors”, ” tricyclic antidepressants”. Amitriptylin 10mg och imipramin 25mg gav en statistiskt signifikant symtomlindring vid IBS med diarré (IBS-D) jämfört med placebo. Dessutom gav tianeptin 12,5mg 3 gånger/dag, som tillhör läkemedelsgruppen selektiv serotonin återupptagsenhancer (SSRE), en likvärdig symtomlindring som amitriptylin 10mg en gång/dag. Skillnaden mellan de två var inte statistiskt signifikant, däremot var studien openlabel och icke-placebokontrollerad vilket gör det svårt att dra någon slutsats. Fluoxetin, som tillhör läkemedelsgruppen selektiva serotonin återupptagshämmare SSRI, gav en statistiskt signifikant effekt jämfört med placebo vid behandling av IBS med förstoppning (IBS-C). Däremot gav paroxetin-CR ingen statistiskt signifikant effekt på buksmärta vid IBS-C jämfört med placebo, dock uppnådde fler i paroxetingruppen den sekundära utfallsvariabeln (global klinisk förbättring) och fick poäng mellan 1 – 2 på skalan Clinical Global Impressions-Improvement (CGI-I).  Baserat på studierna som presenteras i denna litteraturstudie dras slutsatsen att en låg dos TCA är en effektiv och säker behandling vid IBS-D medan SSRI är effektiva och säkra vid behandling av IBS-C jämfört med placebo.

Background Cancer is one of the leading causes of death in Sweden. In order to develop better treatments against cancer we need to better understand it. One area of special interest is cancer metabolism and the metabolic fluxes. As these fluxes cannot be directly measured, modeling is required to determine them. Due to the complexity of cell metabolism, some limitations in the metabolism model are required. As the TCA-cycle (TriCarboxylic Acid cycle) is one of the most important parts of cell metabolism, it was chosen as a starting point. The primary goal of this project has been to evaluate the previously constructed TCA-cycle model. The first step of the evaluation was to determine the CI (Confidence Interval) of the model parameters, to determine the parameters’ identifiability. The second step was to validate the model to see if the model could predict data for which the model had not been trained for. The last step of the evaluation was to determine the uncertainty of the model simulation. Method The TCA-cycle model was created using Isotopicaly labeled data and EMUs (ElementaryMetabolic Units) in OpenFlux, an open source toolbox. The CIs of the TCA-cycle model parameters were determined using both OpenFlux’s inbuilt functionality for it as well as using amethod called PL (Profile Likelihood). The model validation was done using a leave one out method. In conjunction with using the leave on out method, a method called PPL (Prediction Profile Likelihood) was used to determine the CIs of the TCA-cycle model simulation. Results and Discussion Using PL to determine CIs had mixed success. The failures of PL are most likely caused by poor choice of settings. However, in the cases in which PL succeeded it gave comparable results to those of OpenFLux. However, the settings in OpenFlux are important, and the wrong settings can severely underestimate the confidence intervals. The confidence intervals from OpenFlux suggests that approximately 30% of the model parameters are identifiable. Results from the validation says that the model is able to predict certain parts of the data for which it has not been trained. The results from the PPL yields a small confidence interval of the simulation. These two results regarding the model simulation suggests that even though the identifiability of the parameters could be better, that the model structure as a whole is sound. Conclusion The majority of the model parameters in the TCA-cycle model are not identifiable, which is something future studies needs to address. However, the model is able to to predict data for which it has not been trained and the model has low simulation uncertainty.

<p dir="ltr">Skeletal muscle accounts for 40% of total body weight and the homeostasis of muscle tissue is critical in maintaining proper body function. Skeletal muscle develops during the embryonic stages from the muscle progenitor cells derived from the dermomyotome structure. The myogenic progenitor cells contribute to the primary myogenesis by forming the primary myotubes which are the founding structures that the secondary myogenesis continues to build on. A portion of the myogenic progenitor cells makes up the adult muscle stem cells residing in homeostatic muscle tissue. The adult muscle stem cells contribute substantially for the adult muscle regeneration. Due to the significance of the muscle tissue and the importance of muscle stem cells, dysregulation of the muscle homeostasis or the muscle stem cell homeostasis will result in severe pathological conditions such as myopathy.</p><p dir="ltr">Mitochondria are cellular organelles that are responsible for generating energy needed for cellular processes, especially for muscle tissue where muscle contraction requires the presence of ATP. On the other hand, mitochondria also serve as signaling molecules and provide macromolecules for the biosynthesis. FAM210A (Family With Sequence Similarity 210 Member A) protein was shown to impact the lean mass of human subjects yet a detailed study on the effect of FAM210A in skeletal muscle was not performed, nor has the molecular mechanisms through which FAM210A function been elucidated. Therefore, I take on the task to unveil the function of FAM210A in muscle development, muscle homeostasis and muscle stem cell behavior by using a combination of mouse models with different myogenic promoters to target <i>Fam210a</i> at different developmental stages.</p><p dir="ltr">In the first part of the thesis, I investigated the role of FAM210A in post differentiation myofibers. Using the <i>Myl1</i>^<em>Cre</em> driven deletion of <i>Fam210a</i>, I found that <i>Fam210a</i>^<em>MKO</em> had normal development before 3 weeks of age, but the growth was stagnant from 4 weeks on, and the mice did not survive past 8 weeks of age. I found that the assembly of the ribosomes in the <i>Fam210a</i>^<em>MKO</em> was defective, leading to impaired translation which attenuated the muscle atrophy phenotype. I identified through proteomics that the mitochondrial autophagy and proteostatic control pathways were significantly induced yet mitochondrial organization and energetic proteins were downregulated. Metabolomics analysis showed that the signaling metabolite acetyl-CoA was increased in the <i>Fam210a</i>^<em>MKO</em> which led to increased protein acetylation, specifically, we showed that the ribosomal proteins were hyperacetylated, and that the acetylation increase was elicited by the <i>Fam210a</i>-null mitochondria.</p><p dir="ltr">In the second part of the thesis, I investigated the function of FAM210A in muscle progenitor cells. In the <i>FamMKO</i> mice, I found that deletion of <i>Fam210a</i> from embryonic myogenic progenitor cells led to developmental arrest and postnatal death at day 6. In the <i>FamPKO</i> mice, I found that <i>Fam210a</i> is needed for adult muscle stem cell to contribute to regeneration. Loss of <i>Fam210a</i> leads to the regenerative defects when the muscle was exposed to injury cues. We further showed that <i>Fam210a</i> deletion in muscle stem cells resulted in disruption of the proteostatic control over muscle stem cell activation, thereby forbidding the translational increase necessary to facilitate activation and proliferation. Furthermore, I showed that <i>Fam210a</i> deletion leads to excessive OPA1 cleavage, which contributes to the regenerative failure of muscle stem cells as fusion is required for the mitochondrial network remodeling during regeneration. Therefore, <i>Fam210a</i> safeguards the mitochondrial network and proteostasis during regeneration.</p><p dir="ltr">In summary, my studies characterized the functional contribution of FAM210A during embryonic muscle development, muscle mass maintenance and adult muscle stem cell homeostasis. The regulation of FAM210A in these three processes impinge on the translational regulation. My studies further demonstrated the importance of mitochondrial regulated protein translation in skeletal muscle and muscle stem cells.</p>