Abstract The opioid receptors (δ, κ and μ) are family A G protein-coupled receptors (GPCRs) that have an important role in the regulation of pain. Like all GPCRs they have a common structure that consists of seven transmembrane domains with an extracellular amino (N)-terminus and an intracellular carboxyl-terminus. The human δ opioid receptor (h(δOR) has two polymorphic variants. A single-nucleotide polymorphism causes replacement of Phe with Cys at the amino acid position 27 in the receptor N-terminus. The allelic frequency of hδORCys27, the less common variant, is about 10% in Caucasians. In this study, the two hδOR variants were expressed in heterologous expression systems and their biosynthesis was characterized in detail using various cell biological and biochemical techniques. In particular, the role of receptor heteromerization and opioid receptor pharmacological chaperones in processing, maturation and trafficking of the variants was assessed. The hδOR variants showed significant differences in maturation and trafficking. The hδORCys27 had a significantly lower maturation efficiency compared with hδORPhe27. In addition, long-term receptor expression led to the accumulation of hδORCys27 in the endoplasmic reticulum (ER) and also impaired receptor targeting to ER-associated degradation. The hδOR variants also differed at the cell surface, as the hδORCys27 variant was internalized constitutively in a faster and more extensive manner than hδORPhe27. However, the variants had similar pharmacological properties and activated G proteins in an identical manner. This study also showed that hδORCys27 acted in a dominant negative manner and redirected some hδORPhe27 precursors to degradation. This resulted in impaired plasma membrane expression of hδORPhe27 in co-transfected cells. The hδOR variants were found to form heteromers early in the secretory pathway, which is the most likely reason for the dominant negative behavior of hδORCys27 on hδORPhe27. The mechanism of action of opioid receptor pharmacological chaperones, membrane-permeable opioid ligands, was investigated in detail using hδORCys27 and its mutant form hδORCys27-(Asp95Ala) as models. Opioid antagonists were found to be able to bind to and stabilize receptor precursors in the ER and enhance their dissociation from the ER molecular chaperone calnexin. This led to an increase in the number of receptors at the plasma membrane. In addition, hδORPhe27, like hδORCys27, was responsive to antagonist treatment whether the variants were expressed together or individually. / Tiivistelmä Opioidireseptorit kuuluvat G-proteiinikytkentäisiin reseptoreihin, ja niillä on tärkeä rooli kipuaistimuksen säätelyssä. Ne ovat solukalvoproteiineja, joiden aminohappoketju läpäisee kalvon seitsemän kertaa. Reseptorien aminoterminaalipää sijaitsee solun ulkopuolella ja karboksiterminaalipää solun sisällä. Ihmisen δ-opioidireseptori esiintyy kahtena polymorfisena muotona, Phe27:nä ja Cys27:nä, joissa aminohappo 27 on joko fenyylialaniini (Phe) tai kysteiini (Cys). Cys27 on harvinaisempi muoto, ja sen yleisyys on noin 10 % eurooppalaista alkuperää olevalla väestöllä. Tämän väitöskirjan tavoitteena oli tutkia δ-opioidireseptorin varianttimuotojen biosynteesiä reseptoriproteiinia tuottavissa heterologisissa solumalleissa (HEK293- ja SH-SY5Y-solut) solubiologisilla ja biokemiallisilla menetelmillä.. Väitöskirja osoittaa, että δ-opioidireseptorin varianttimuotojen välillä on eroa prosessoinnissa. Cys27-varianttia kuljetetaan endoplasmakalvostosta solun pinnalle vähemmän kuin Phe27-varianttia, ja pitkäaikainen reseptorituotanto johtaa vastasyntetisoituneiden reseptorien kerääntymiseen solun sisälle. Samalla reseptorien ohjaus proteasomihajotukseen heikkenee. Soluissa, jotka tuottavat molempia varianttimuotoja samanaikaisesti, Cys27-variantin havaittiin ohjaavan myös Phe27-varianttia proteasomihajotukseen vähentäen sen kuljetusta solun pinnalle. Tämä Cys27-variantin dominanttinegatiivinen ominaisuus johtuu todennäköisesti siitä, että variantit muodostavat dimeerisen rakenteen endoplasmakalvostossa. Havaittiin myös, että Cys27-varianttireseptorit ohjataan solun pinnalta lysosomihajotukseen tehokkaammin kuin vastaavat Phe27-varianttimuodot. Prosessointieroista huolimatta variantit eivät poikkea toisistaan farmakologisilta ominaisuuksiltaan, ja ne aktivoivat G proteiineja samalla tavalla. Väitöskirjassa tutkittiin myös farmakologisten kaperonien toimintamekanismeja käyttämällä mallina δ-opioidireseptorin Cys27-varianttia ja sen pistemutaatiota (Asp95Ala). Farmakologisten kaperonien eli reseptorispesifisten ligandien todettiin sitoutuvan reseptoreihin endoplasmakalvostossa ja stabiloivan niiden rakennetta, mikä vähentää reseptorin ja proteiinien laadunvalvontaan osallistuvan kaperonin, kalneksiinin, välistä vuorovaikutusta. Tämä johtaa reseptorien määrän kasvuun solun pinnalla.

La survie des cellules T naïves est essentielle au bon fonctionnement du système immunitaire à long terme. Les rats BBDP (Bio-breeding Diabetes prone) sont caractérisés par une haute prédisposition au développement du diabète ainsi que par une diminution significative du nombre de cellules T naïves. Ces rats comportent une mutation de type décalage de lecture dans le gène codant pour «GTPase Immunity-Associated Protein 5» (Gimap5) ce qui entraine l’apoptose des lymphocytes T. Le mécanisme par lequel la déficience de la protéine GIMAP5 conduit les cellules T à la mort est actuellement méconnu. GIMAP5 a également été associée à différentes maladies auto-immunes, ce qui suggère son influence dans l'homéostasie des lymphocytes T. Des résultats antérieurs de notre groupe de recherche ont montré que l'absence de GIMAP5 entraîne une diminution du flux de Ca2+ ainsi qu’une réduction de la capacité mitochondriale à emmagasiner du Ca2+ suite à la stimulation du TCR. Cependant, GIMAP5 n'est pas une protéine mitochondriale. Afin de mieux comprendre le rôle de GIMAP5 dans la biologie des cellules T, au cours de mes études doctorales, je me suis concentré sur la localisation cellulaire de la protéine ainsi que sur son rôle dans l'homéostasie du Ca2+. Comme modèle d’étude, j'ai établi des lignées cellulaires HEK293T stables pour l’expression de GIMAP5, ainsi que pour différents mutants et variantes de la protéine. Ceci m’a permis d’élucider l'importance du domaine transmembranaire (TM) pour la localisation et le rôle physiologique de GIMAP5 ainsi que la différence entre les deux variantes de cette protéine. Mes résultats ont permis de montrer que l'expression de Gimap5 ne semble pas être nécessaire après l’activation des lymphocytes T. En parallèle, j'ai confirmé nos observations antérieures qui démontrent l’influence de GIMAP5 dans l'homéostasie du Ca2+ et sa colocalization avec les microtubules. En outre, j'ai montré que GIMAP5 se trouve dans des structures de type vésiculaire, particulièrement dans la membrane lysosomale où son domaine TM est essentiel à son bon fonctionnement et localisation. Mes résultats suggèrent que les mitochondries exhibent un défaut dans leur capacité à emmagasiner du Ca2+ au niveau basal, ainsi que suite à l’activation du TCR. Enfin, j'ai démontré pour la première fois, que l'influence de GIMAP5 sur le stockage de Ca2+ lysosomal peut avoir un impact sur la survie des lymphocytes T. D’après ces observations, une des fonctions probables de GIMAP5 serait d’empêcher la fermeture prématurée des canaux de relâche calcique. Finalement, GIMAP5 pourrait être engagé dans des mécanismes visant à prolonger et raffiner la signalisation du Ca2+ dans les cellules T. Bref, la régulation du Ca2+ lysosomal médié par GIMAP5 est essentielle à la survie de cellules T naïves. / Abstract: Healthy and long-term survival of naïve T cells is essential for proper functioning of the immune system. In bio-breeding diabetes prone (BBDP) rats, there is a critical decrease in the number of naïve T cells. In these rats, a recessive frameshift mutation in the GTPase of Immune-Associated Protein 5 (Gimap5) gene induces lymphocytes to undergo spontaneous apoptosis. The death of T cells driven by a deficiency of the GIMAP5 is currently not fully understood. Interestingly, different autoimmune diseases have shown an association with perturbations in the Gimap5 gene, which further suggests its influence in basal lymphocyte homeostasis. Previous findings by our group have shown that the absence of GIMAP5 results in a decrease calcium flux following TCR stimulation and an impaired capacity of the mitochondria to buffer calcium entry. However, GIMAP5 is not a mitochondrial protein. During my Ph.D. studies, I focused on clarifying the cellular localization of GIMAP5 as well as its function in Ca2+ homeostasis in order to further understand its role in T cell biology. As a model, I established HEK293T cells stable for the expression of the different mutants and variants of the GIMAP5 protein. Where I uncovered the importance of the transmembrane domain (TM) for GIMAP5 localization and physiological role, as well as the differences between the two variants of GIMAP5. The results obtained show that the expression of Gimap5 is no longer needed after T cells activation. Moreover, our previous observations were confirmed and expanded upon regarding GIMAP5’s influence on Ca2+ homeostasis and colocalization with the cytoskeleton. It was also shown that GIMAP5 localizes to vesicular-like structures, particularly to the lysosomal membrane, where its TM domain is critical for proper functioning and localization. My results suggest that the mitochondria might be impaired to uptake as well as retain Ca2+ at their full capacity in the absence of GIMAP5. Finally, I observed for the first time that GIMAP5’s influence on lysosomal Ca2+ storage could impact lymphocyte survival. These results suggest that GIMAP5 may work as a backup mechanism to prevent premature closure of Ca2+ channels and Ca2+ influx or as a mechanism to prolong and refine Ca2+ signaling in T cells.

La progression tumorale repose sur l'acquisition progressive d'anomalies génétiques qui vont conduire à la prolifération dérégulée de ces cellules. Il existe cependant des systèmes de protection contre cette progression tumorale que l'on appelle systèmes de sauvegarde. Ainsi, pour se transformer, la cellule tumorale doit franchir ces barrières anti-tumorales. Les résultats de mon travail de thèse, qui avait pour objectif initial d'identifier les altérations moléculaires précoces de l'oncogenèse, m'ont permis de mettre en évidence un nouveau mécanisme de sauvegarde anti-tumoral. Pour cette étude, un modèle d'étude in vitro de l'initiation et de la progression tumorale déclenchée par l'oncogène RET développé par notre équipe a été utilisé. Grâce à l'utilisation de ce système, nous avons pu montrer que le Réticulum Endoplasmique (RE) est un senseur efficace de l'altération du métabolisme glucidique déclenchée par les signalisations oncogéniques, et que le stress qu'il subit alors, conduit à l'apoptose. Ce travail a permis de mettre mis en évidence que les cellules malignes qui franchissent cette barrière peuvent alors bénéficier d'un effet pro-tumorale du SRE. Ainsi, les résultats présentés dans ce manuscrit offrent une meilleure compréhension du rôle complexe que joue le SRE dans la cancérogénèse / Carcinogenesis involves not only inactivation of tumourigenesis barriers, but also alterations in energy metabolism to fulfil the synthetic and bioenergetic requirements for fast and uncontrolled growth. Our study supports a model in which the ER acts as a node between altered glucose metabolism and tumourigenesis barriers. This major site in the cell for protein folding and maturation, can sense glucose limitation that results from oncogenic-mediated increased glucose demand, and consequently trigger unfolded protein response-dependent apoptosis. As such, the ER functions as a surveillance mechanism that suppresses the emergence of tumour cells. Overcoming this early barrier involves a specific attenuation of the pro-apoptotic PERK-CHOP branch of the unfolded protein response, a cellular adaptation that in turn may favour malignant progression. These observations bring new insights into the complex role of the unfolded protein response during tumourigenesis

No description available.

La mitochondrie et le réticulum endoplasmique (RE) forment un réseau dans les cellules qui contrôle la fonction et le destin cellulaire. La mitochondrie de la cellule ß pancréatique joue un rôle central dans la sécrétion d’insuline en réponse au glucose de par sa capacité à produire de l’ATP. Le RE lui prend en charge la mise en conformation de l’insuline et joue le rôle de stock calcique. Ces 2 organites se rejoignent au niveau de points de contact appelés Mitochondria Associated endoplasmic reticulum Membranes (MAMs,). Les MAMs sont le siège d’échanges calciques et lipidiques entre les 2 organites. Les altérations de la mitochondrie et du RE ont été montrées comme des facteurs contribuant au développement du diabète de type 2. L’implication des MAMs n’a cependant jamais été étudiée dans la cellule ß.La glucotoxicité provoquée par une exposition chronique à des concentrations élevées de glucose, est un facteur clé de la dysfonction ß pancréatique au cours du diabète de type 2. J’ai pu démontrer que la glucotoxicité augmentait la fission mitochondriale et le nombre de MAMs dans les cellules bêta humaines et INS-1E mais que ces MAMs présentaient des défauts d’échanges calciques, pouvant ainsi contribuer au défaut de la sécrétion d’insuline. J’ai ensuite modulé les MAMs soit via une stimulation aigue au glucose soit par l’utilisation d’un siRNA qui rompt partiellement les contacts entre le RE et la mitochondrie ou par l’utilisation d’un linker qui artificiellement force ces contacts. La stimulation aigue au glucose augmente les MAMs et le transfert de calcium du RE vers la mitochondrie alors que la rupture des contacts diminue la secretion d’insuline. Enfin le linker en forçant les rapprochements RE-mitochondrie mime les effets de la glucotoxicité.Ce travail, constitue la première étude structurelle et fonctionnelle des MAMs dans la cellule ß pancréatique, éclairant leur rôle dans la dysfonction ß pancréatique lors du développement du diabète de type 2 / Mitochondria and endoplasmic reticulum (ER) form a network in cells that control cellular function and fate. Mitochondria play a central role in insulin secretion in ß cell by its ability to product ATP. ER takes in charge of insulin folding and is the major cell calcium store. Both organelles interact at contact sites, defined as mitochondria-associated membranes (MAMs), a multiprotein complex implicated in calcium transfer and lipid exchange . Alterations of mitochondria and ER have been shown to contribute to metabolic disorder such as type 2 diabetes. MAMS were recently implicated in the regulation of glucose homeostasis But the role of MAMs in ß cells is still largely unknown and their implication in glucotoxicity-associated ß cell dysfunction remains to be defined.Here, I report that acute glucose stimulation stimulated ER-mitochondria interactions and calcium (Ca2+) exchange in INS-1E cells, whereas disruption of MAMs altered glucose-stimulated insulin secretion (GSIS). Conversely, chronic incubations with high glucose of either INS-1E cells or human pancreatic islets altered GSIS, and concomitantly reduced ER Ca2+ store, increased mitochondrial Ca2+ and reduced ATP-stimulated ER-mitochondria Ca2+ exchanges, despite an increase of organelle interactions. Furthermore, glucotoxicity-induced perturbations of Ca2+ signalling are associated with ER stress, altered mitochondrial respiration and mitochondria fragmentation, and these organelle stresses may participate to increased organelle tethering, as a protective mechanism. Lastly, sustained induction of ER-mitochondria interactions using a linker induced mitochondrial fission and altered GSIS.Therefore, dynamic organelle coupling participates to GSIS in ? cells and over-time disruption of organelle Ca2+ exchange might be a novel mechanism contributing to glucotoxicity-induced ß cell dysfunction in type 2 diabetes

The master thesis describes the analysis and proposal of changes of information system for the village Hrušovany u Brna. The analysis of information system was done mainly using the method HOS8. Changes were made on the base of the analysis, mainly the new part of the information system, which collects data about waste sorting in families. Introduction of these changes bring new information to the management and contribute to better waste management in the village.

The aim of this thesis is to design a web application for software project management in the Lokola s.r.o. company. First, the currently used project management software is analysed. Next, the requirements of Lokola s.r.o. towards the new application are captured and analysed. Based on the analysis, corresponding use cases, data model and object design of the new application are created.

Die vorliegende Studie untersucht die zugrunde liegende Frage, ob die Sprechapraxie und die aphasisch-phonologische Störung anhand phonetischer Entstellungen und phonematischer Paraphasien bei Diphthongen und Monophthongen voneinander unterschieden werden können. Ergänzend werden messphonetische Daten wie Vokal- und Wortdauern, der erste und zweite Vokalformant und die Voice Onset Time bei stimmlosen Plosiven im Silbenanlaut vergleichend herangezogen. Dazu werden drei Gruppen à vier Probanden untersucht: Gruppe SAX (mit Sprechapraxie), Gruppe APH (mit aphasisch-phonologischer Störung) und Gruppe NOM (sprachgesunde Kontrollgruppe). Es wird ein Nachsprechtest von 104 deutschen, meist monomorphematischen, einsilbigen Nomina, 52 einfache (CVC) und 52 komplexe (CCVC und CVCC) Silben, durchgeführt. Jeder Vokal wird durch acht meist unterschiedliche Wörter überprüft. Die Reaktionen werden mit dem phonetischen Analyseprogramm „Praat“ (Version 5.2.22, Boersma & Weenink, 1992–2011) segmentiert sowie ohren- und messphonetisch analysiert. Die statistische Auswertung erfolgt mit R (R Foundation) und R Studio (Version 0.98.1103, 2009–2014). Die Ergebnisse liefern Hinweise auf störungsspezifische Fehler bzw. Pathomechanismen der Sprechapraxie. Die Gruppe SAX produziert signifikant mehr phonetische Entstellungen bei Monophthongen und Diphthongen sowie signifikant längere Wortdauern als die Gruppe APH. In der Gruppe SAX sind einige Vokale nur teilweise entstellt, wie z. B. initial atypisch behauchte oder gerundete Vokale. Auch zeigen sich die Formantwerte in der Gruppe SAX variabler als in der Gruppe APH und der Gruppe NOM. Die Ergebnisse verweisen auf ein angenommenes Timing-Defizit bei der Planung und Kontrolle sprechmotorischer Bewegungen der Sprechapraxie. / This study analyses the underlying question if it is possible to distinguish apraxia of speech (SAX) and phonemic aphasia (APH) by phonetic distortions and phonological paraphasia of monophthongs and diphthongs. Phonetic measurements like the duration of vowels and words, the Voice Onset Time of voiceless plosives in the onset of syllables and the first and second formant will be analyzed as well. Three groups of four subjects are studied: Group SAX (no/mild aphasia), group APH (without apraxia of speech), group NOM (without any speech disorder). A repetition task comprising 104 German mostly monomorphemic, monosyllabic nouns, 52 simple (CVC) and 52 complex (CCVC and CVCC) syllables, is performed. Each of the vowels is tested in eight mostly different words. The reactions will be segmented, phonetically measured, and analyzed by ear with the help of the program “Praat” (Version 5.2.22, Boersma & Weenink, 1992–2011). The statistical analysis is conducted with R (The R Foundation), within the “R-Studio” software suite (Version 0.98.1103, 2009–2014). The results show some indications of failures and pathological mechanisms of apraxia of speech. Group SAX produces significantly more phonetic distorted monophthongs and diphthongs and significantly longer word durations than group APH. Some vowels are just partly distorted, for example, in form of atypical initial aspirated or rounded monophthongs. Also the formants show greater variability in group SAX than in groups APH and NOM. The results suggest a timing deficit during planning and control of speech movements in apraxia of speech.

One of the most important factors in accessing dental care is having dental insurance. For people with low incomes, Medicaid is the main source of health insurance. Medi-Cal is California’s Medicaid program. Adult dental services were mostly eliminated in Medi-Cal in 2009 due to the economic downturn and partially restored in 2014. The objective of this study is to evaluate the effect of change in Medi-Cal dental coverage, specifically the partial restoration of adult dental coverage in 2014, on dental care utilization among Medi-Cal beneficiaries. The partial restoration significantly increased the utilization rates in dental clinics from 2014 to 2017 (22% in 2017 vs. 12% in 2013) for the overall population. However, the magnitude of increase differs in different age groups and ethnic groups. More statistically significant findings show greater utilization rates among beneficiaries of 19-64 than 65-74 and 75+ years old. Also, more significant findings show lower utilization among Black than White, Hispanic or Asian beneficiaries. The partial restoration significantly reduced the dental related ER visits among Medi-Cal beneficiaries from 2015 to 2017. However, the reduction is largely seen in beneficiaries of 19-64 years old in the ethnic groups of White and Black with reductions of 20 and 15 visits per 1,000 enrollees respectively in 2017 comparing to 2013. The dental related ER visits were lower for Hispanics and Asians, and remained very low among those 65 years old and above. In addition, the partial restoration resulted in increases in participation of dental care providers in the Medi-Cal program.

In früheren Studien zum L2-Wortschatzerwerb wurden die Auswirkungen des visuellen Kontexts auf das Lernen und die Verarbeitung von Wörtern und Kollokationen in der L2 untersucht. Es wurde festgestellt, dass die Erstsprache einen positiven Transfer auf das Lernen einer Zweitsprache hat, wenn die Wörter Ähnlichkeiten aufweisen. Darüber hinaus wurden die Einflüsse der kognitiven Fähigkeiten der Lernenden und ihres Erwerbsalters (AoA) auf das L2-Vokabellernen unter verschiedenen Bedingungen des L2-Vokabellernens festgestellt. Ziel der vorliegenden Arbeit war es, die Auswirkungen des visuellen Kontexts und des Transfers auf das Lernen von L2-Vokabeln weiter zu untersuchen und zu klären, wie die kognitiven Fähigkeiten und das Erwerbsalter diese Auswirkungen in einem bestimmten L2-Lernkontext beeinflussen. Im Detail wurden Effekte der Ereignisdarstellung (d.h. nicht-sprachlicher visueller Kontext) untersucht sowie Transfereffekte aus der Erstsprache in die Zweitsprache im Bezug auf das Lernen von L2-Phrasenwortschatz (d.h. Verb-Nomen-Phrasen) bei erwachsenen Anfängern. Wir führten Kurzzeitexperimente zum L2-Wortschatzerwerb durch, bei denen wir die Reaktionszeiten maßen. Zwei weitere Forschungsfragen untersuchten, ob es Zusammenhänge zwischen der AoA oder den kognitiven Fähigkeiten der Lernenden und ihrem Lernerfolg beim Vokabellernen in einer kurzfristigen L2-Lernumgebung gibt. Die Ergebnisse zeigten, dass erwachsene L2-Anfänger*innen beim L2-Vokabellernen von visuellen Darstellungen profitierten: Sie waren unter Lernbedingungen mit Ereignissen genauer und schneller als unter Lernbedingungen ohne Ereignisse. Diese Effekte konnten in drei Experimenten nicht nur mit jungen Erwachsenen im Alter von 18 bis 31 Jahren nachgewiesen werden, sondern galten auch für Erwachsene im frühen und späten mittleren Alter von 32 bis 65 Jahren. Die vorangegangene Forschung deutete darauf hin, dass die Ähnlichkeit zwischen L1 und L2 das L2-Lernen beeinflussen könnte, jedoch nicht in diesem spezifischen L2-Lernkontext. Darüber hinaus wurde der AoA der Probanden manipuliert, was dazu führte, dass junge Erwachsene in den kognitiven Tests und bei den L2-Lernaufgaben besser abschnitten als die anderen beiden Gruppen. Basierend auf den Ergebnissen unserer Forschung konnten wir herausfinden, welche Faktoren den Erfolg des L2-Wortschatzerwerbs bei erwachsenen L2-Anfängern stark beeinflussen und dass das Lernen von L2-Phrasenwortschatz mit dargestellten Ereignisfotos angewendet werden kann. / Previous studies of L2 vocabulary learning presented visual context effects on L2 word and collocation learning and processing. It was found that L1 has a positive transfer in L2 learning when words have similarities. Furthermore, the influences of learners’ cognitive ability and their age of acquisition (AoA) in L2 vocabulary learning have been found in diverse L2 vocabulary learning conditions. The present dissertation aimed to further investigate the effects of visual context and transfer on L2 learning, as well as how cognitive ability and AoA influence any such effects in a particular L2 vocabulary learning context. In detail, we investigated event depiction (i.e., non-linguistic visual context) effects and L1–L2 transfer effects on L2 phrasal vocabulary (i.e., verb-noun phrases) learning for adult beginners. We conducted short-term L2 vocabulary learning experiments during which we measured reaction times. Two other research questions examined whether there are relationships between learners’ AoA or their cognitive ability and their L2 vocabulary learning success in a short-term L2 learning setting. Results showed adult L2 beginners benefited from visual depictions in L2 vocabulary learning: They were more accurate and faster in event-present learning conditions than in event-absent learning conditions. These effects were not only replicated with young adults aged 18 to 31 in three experiments, but they also extended to early and late middle-aged adults aged 32 to 65. The prior research suggested that the L1–L2 similarity might influence L2 learning, but not in our L2 learning context. In addition, the AoA of subjects was manipulated, which resulted in young adults performing in the cognitive test and L2 learning tasks best compared to the other two groups. Based on the findings of our research, we were able to identify which factors strongly influence L2 vocabulary learning success for L2 adult beginners and that L2 phrasal vocabulary learning with depicted event photographs can be applied.