The primary cilium is vital for the health and well being of the organism. Diseases of the cilia, referred to as ciliopathies, present with overlapping phenotypes due to a protein defect in the same organelle. Three such disorders are Nephronophthisis (NPHP), Bardet-Biedl Syndrome (BBS), and Senior-Loken Syndrome (SLS). Mutations in serologically defined colon cancer antigen 8(SDCCAG8 [MIM 613524]) have been associated with all of these disorders (BBS16, NPHP10, SLSN7). Little is known about the role of SDCCAG8 in ciliary function, and the mechanisms through which SDCCAG8 leads to ciliopathy phenotypes are potentially novel and may identify therapeutic targets for treating clia related disorders. My work aimed at elucidating these mechanisms utilizing in vitro and in vivo models to identify specific interactors of SDCCAG8. Here, we show an interaction with the multi-aminoacyl tRNA synthetase complex (MSC) and more specifically, with the aminoacyl interacting multifunctional protein 2 (AIMP2). We also determined that the interaction between these genes is dependent on the N-terminus of AIMP2 and a region in the C-terminus of SDCCAG8. Further work characterized the importance of SDCCAG8 in AIMP2 nuclear localization. Loss of SDCCAG8 results in increased AIMP2 nuclear localization and downstream upregulation of p53. We also characterized an Sdccag8 mouse model and assessed its utility as a ciliopathy model. We performed a phenotypic characterization of this model and identified a genomic deletion encompassing a neighboring gene, Akt3. Due to this finding, we suggest that individuals interested in this mouse model proceed with caution. In addition, we used this model to identify a potential modifier locus of lethality. Overall, the work presented in this thesis advances the understanding of the biology of SDCCAG8 and its role in the cell.

This thesis is on the basis of searching EWOM actively and attempt to treat the motivation of using discussion board, and how these motivations explain the influence of discussion board. Reviewing literatures, the thesis generalize the motivations of searching WOM actively and use product involvement to be situational variable in order to explore that the motivation and the consequence of using different discussion board. The thesis adopted bulletin board systems to be the research field, and distributed questionnaires. The research found that though consumers had different motivations of using discussion boards while facing products with diverse level of involvement, in fact, they normally take ¡§information searching¡¨ and ¡§recognition seeking¡¨ as the main motivations. Further, the explanatory power of these motivation factors on the consumers¡¦ behaviors changed by the discussion boards will differ with the product involvement.

Luckan mellan människors attityd och beteende när det gäller miljö är ett problem och för att nå hållbar utveckling måste människors beteenden förändras. Denna uppsats ämnar undersöka huruvida en kombination av faktorer och metoder framgångsrikt kan användas för att adressera komplexiteten i mänskligt beteende och koppla dem till ett antal beteendepåverkande metoder och modeller. Beteendebaserad säkerhet (BBS) är en arbetsmiljömetod som bygger på beteendevetenskapens ABC-modell (signal-beteende-konsekvens) och syftar till att först ändra beteendet vilket sedan ger en attitydförändring. En tes i denna studie är att faktorer från BBS kan appliceras på miljöbeteende, något som inte tidigare har undersökts.  Faktorer från beteendevetenskap, BBS, nudging och Hawthorneeffekten slogs samman i en insats i syfte att förbättra källsorteringsbeteendet på Sydkraft Hydropower AB i Sundsvall. Studien utfördes under totalt fem veckor och mätte effekten av insatsen genom vägning, plockanalys, enkät och LCA. Resultatet visar en liten effekt genom en minskning av felsorterade artiklar, effekten var dock inte kvarstående vilket gör vidare och längre studier nödvändiga för att undersöka beteendeförändring över tid. I studien genomfördes också en livscykelanalys på kaffemuggar och resultatet visade att porslinsmuggen har lägre miljöbelastning än pappersmuggen efter 399 respektive 54 användningar, beroende på vald analysmetod. / The environmental attitude-behavior gap of people is problematic and to reach sustainable development people´s behavior has to change. This paper discusses a number of behavioral methods and looks into whether a combination of methods and factors can successfully be applicable to address the complexity of human behavior. Behavior-based safety (BBS) is a method that builds upon the ABC-model of behavioral science and seeks to change the behavior first which then leads to attitude changes. A thesis in this study is that factors från BBS can be applicable to environmental behavior, a theory not previously examined. Factors from behavioral science, BBS, nudging and the Hawthorne effect were merged in an intervention in order to improve the recycling behavior at Sydkraft Hydropower AB in Sundsvall. The study was conducted over a five week period and the result showed a small effect on the fault sorting of waste. The effect did not remain after intervention ended which makes further and longer studies necessary to examine behavioral change over time.  An LCA on coffee mugs was also conducted and the result showed that the porcelain mug is more environmentally friendly than the paper mug after 399 and 54 uses respectively, depending on the chosen method.

Grundstenen för den svenska ärekränkningsrätten utgörs av förtalsbestämmelsen i 5 kap. 1 § BrB. Lagen infördes år 1965 i samband med den stora reformen av brottsbalken som ersatte strafflagen.[1] Sedan förtalsbestämmelsen infördes har kränkningsskyddet kompletterats med bestämmelsen om olaga integritetsintrång och BBS-lagen. Förtalsbestämmelsen innebär en kriminalisering av lämnandet av uppgifter som kan leda till att andras missaktning riktas mot den som uppgifterna utpekar. Sådana uppgifter beskrivs i propositionen bestå av uppgifter om någons kriminalitet, sexualitet eller uppgifter som på annat sätt kan vara kränkande för den som utpekas. BBS-lagen infördes för att föreskriva tillhandahållaren av en webbplats att radera innehåll på webbplatsen som uppenbart utgör sådant som är olagligt enligt BBS-lagen 5 §. Utöver kravet på tillhandahållaren att radera otillåtna inlägg skulle bestämmelsen också agera normgivande på internet. Vidare infördes därefter bestämmelsen om olaga integritetsintrång i syfte att förbjuda spridningen av kränkande bilder och videos. Sådana bilder eller videor kan vara nakenbilder eller bilder på någon i ett utsatt tillstånd. Förtalsbestämmelsen innehåller emellertid ingen grund för att radera kränkningar eller inlägg som fastställts utgöra förtal. Vidare fastslog HD i NJA 2020 s. 917 att brottet inte heller bedöms perdurerande vilket innebär att kvarlämnandet av sådana kränkningar inte kan leda till straffansvar för den som publicerat kränkningen. För bestämmelsen om olaga integritetsintrång innebär avgörandet i NJA 2020 s. 917 att det saknas möjlighet att straffa den som underlåter att radera en kränkning som utgör olaga integritetsintrång. Om domstolen bedömer att det vid intrångets publicering fanns ett medgivande att publicera bilderna, saknas det betydelse om ett sådant medgivande dras tillbaka. Detta innebär att gärningsmannen inte kan straffas för att inte radera kränkningen oavsett vad som sker efter publiceringen av kränkningen. Ansvaret för att radera kränkningen övergår istället på tillhandahållaren med anledning av BBS-lagen. För tillhandahållaren ges dock ett spelrum på 1–2 veckor där tillhandahållaren får tid att utvärdera inlägg och radera dessa om de bedöms olagliga. Under denna tidsperiod kan användare spara inläggen eller innehållet, för att sedan sprida innehållet vidare innan kränkningen förhoppningsvis raderas av tillhandahållaren. Förtal omfattas emellertid inte i ansvaret som utgår genom BBS-lagen, vilket innebär att den som har en webbplats inte behöver radera inlägg som bedömts utgöra förtal. Kränkningar som utgör förtal kan således kvarlämnas efter fällande dom utan konsekvenser och kränka den utpekade utan begränsning. I samband med internets framfart har antalet anmälningar för ärekränkningsbrott ökat explosionsartat, med över 600%, sedan år 1990. Förra året anmäldes cirka 12 000 ärekränkningsbrott medan endast 46 domar meddelades för ärekränkningsbrotten. Det låga antalet domar tycks främst bero på den särskilda åtalsregeln som stadgas i 5 kap. 5 § BrB och innebär som stadgar att endast om det ”anses påkallat från allmän synpunkt” ska anmälningen utredas av en åklagare.[2] Med den explosionsartade utvecklingen av anmälda kränkningar innebär åtalsregeln att en oerhört begränsad andel av alla brott utreds, vilket innebär att den som utsätts för förtal inte kan förvänta sig något stöd av staten. Den bristande inblandningen av åklagare i kombination med uteblivna möjligheter att radera de få kränkningar som leder till ansvar, innebär att skyddet inte fungerar på det sätt lagstiftaren avsett. Förtalsbestämmelsens syfte är att skydda individer från kränkningar som drabbar deras plats i samhället, men när kränkningar inte raderas undermineras detta skydd. Den som bedöms ha haft någon typ av medgivande vid publiceringstillfället kan inte dömas för olaga integritetsintrång, även om senare omständigheter kan visa att publiceringen kränker den som publiceringen avser, vilket följer av NJA 2020 s. 917. Innan tillhandahållarens ansvar att agera inträder finns även en tidsmässig frizon där kränkningarna hinner spridas och kränka offret utan konsekvenser för vare sig tillhandahållaren eller den som publicerat kränkningen. Den nuvarande ordningen lämnar tydliga hål och skyddar inte brottsoffren på det sätt lagstiftningen avser.

本研究設定參與批踢踢美妝版討論的年輕彩妝族群為目標研究對象，假設透過彩妝族群群體討論彩妝議題的方式，不僅可以掌握彩妝活動本身的形貌、內容與特性；更可以由討論呈現看出彩妝實踐者在日常生活中執行彩妝活動的方式，以及其對彩妝活動投入的情感乃至於相關的價值傳遞，藉此得以推敲彩妝族群熱衷於化妝的理由，解析美妝論述的內涵。 綜合網路文本分析、深度訪談與田野觀察三法蒐集資料，將網路社群互動特性區隔為媒介與議題兩大面向，受媒介特性影響BBS美妝版之互動有團體意識、網路從眾性、網路規則與團體極化四大特色，回歸議題討論方式則可區隔為消費、妝容打造技巧與意見交流三大類型討論。由此可知，「美的意識」與「化妝的價值」是美妝論述的重要核心，並據此結合學理發展討論進行深度概念分析。 本研究認為化妝第一層次的意義是融入社會的具體策略，行動者認為透過此策略得以幫助自己以較有利的正向姿態進入社會生活，這不僅肇於實踐者將化妝與「正面特質」高度連結，更重要的是生活中化妝儀式的執行過程的勞動成品，除了更「好」的身體外，還有稱為「自信」的精神成分推動著化妝儀式的永續執行。此外，化妝的正向感受亦來自過程中對於器物與技法的掌握控制，化妝活動的執行並非渾然天成的性別天賦，而是學習教養的歷程；技法操演的遊戲樂趣、對彩妝品項的物件愛戀，創造了彩妝實踐同中有異的細微差別，帶來探索多變的快意。擁有並隨心所欲掌握那些許的不同，是推動每日演練化妝並從中得到難以言傳之滿足感的深層動力。 化妝作為當代日益普及的社會現象，作為年輕世代、網路彩妝社群的特殊文化現象，不可單純由消費社會印象管理的角度解讀，亦不可僅由性別批判觀點切入。本研究一方面不忽略消費社會所提供之場景，特別是化妝活動對商品消費的深度涉入，以及消費社會對身體裝飾提供之大量參考文本，提供本研究別具備脈絡的解讀觀點。另一方面亦不忽略化妝作為女性特殊經驗的觀點，重視且回歸受訪者真實經驗為論證基礎，同理彩妝實踐者之情感並認可其能動性，落實真正實踐者發聲的研究特性，並不忘環境結構對個體之影響，提出具脈絡的社會性觀點陳述解釋彩妝文化現象，是為本文最具特色與價值的研究貢獻。 / This article takes members of virtual community on PTT’s MakeUp conference as main research target. It is assumed that that the makeup issues discussed within bulletin board conference not only depicts the figure and key factors of makeup activity but also proves makeup as an important roles in daily life. All above are deep influenced and composed by beliefs or ideologies of contemporary social context and these insights show us a way to find answers to the question: why girls are so obsessed with makeup. Through text analysis of conference within BBS, interviewing in depth and field research, this article categorizes the characteristics of communication within MakeUp into two perspectives: media oriented and topic oriented. The former based on the emphasis of virtual community perspective includes community solidarity, conformity, netiquette and polarization. The later based on the viewpoint of the topic under discussion includes consumption, makeup skill sharing and opinion trade. This shows the consciousness of being beautiful and the value of makeup are the core of cosmetic discourse. This research reveals that the behavior of makeup signifies two layers of meanings nowadays. The first layer is to take makeup as a beneficial posture for entering social or public life. This fact demonstrates: (1) the high connection between positive values and makeup (2) positive thinking toward applying cosmetics (while these labor products are made) -- Approaching a nicer body and ‘self-confidence’ sustainingly motivates the ritual. Besides, the complete control over cosmetics goods and the face-building process are also the source of pleasure which is not only the second meaning of makeup but also the deeper driving energy of daily makeup ritual. Taking makeup as a spreading cultural phenomenon, it can not be understood from single viewpoint such as consumerism or feminism. For this reason, this article on the one hand takes the consumer society as a background context to get the idea of using cosmetics to make-up the face in daily life. It on the other hand goes deeply into the experiences and practice of those who really love makeup. Through these aspects, this essay eventually gives a sketch for contemporary makeup culture study on both social structure and personal agency as a major contribution.

Le syndrome de Bardet-Biedl (BBS) est une ciliopathie syndromique associant une rétinopathie pigmentaire, une polydactylie post-axiale, une obésité, un hypogonadisme, des anomalies rénales et des troubles des apprentissages. Le cil primaire est présent à la surface de la quasi totalité des cellules de l’organisme et joue un rôle d’antenne cellulaire captant les signaux extérieurs pour les transmettre à la cellule. A ce jour 21 gènes BBS ont été identifiés codant des protéines ayant une fonction ciliaire. Au cours de ce travail, nous avons identifié 3 nouveaux gènes BBS (SDCCAG8/BBS16, LZTFL1/BBS17, BBIP1/BBS18) et confirmé l’implication de IFT172/BBS20. Nous avons également établi des corrélations génotype-phénotype : absence de polydactylie et insuffisance rénale associées aux mutations dans BBS16 ; polydactylie mésoaxiale et atteinte rénale associées aux mutations dans BBS17 ; possible association d’une polydactylie préaxiale aux mutations dans BBS20. Enfin, nous décrivons sur le plan clinique et moléculaire la plus grande cohorte de patients BBS à partir d’une base de données clinico-biologique mise en place au cours de ce travail. / Bardet-Biedl syndrome (BBS) is a syndromic ciliopathy associating with retinitis pigmentosa, postaxial polydactyly, obesity, hypogonadism, renal anomalies and learning difficulties. The primary cilium is antenna-like structure at the surface of the cell. 21 BBS genes are identified and the corresponding proteins are related to primary cilium structure and function. In this study, we identified 3 new BBS genes (SDCCAG8/BBS16, LZTFL1/BBS17, BBIP1/BBS18) and we confirmed the implication of IFT172/BBS20 in this syndrome. We also established strong genotype-phenotype correlations: absence of polydactyly and early renal failure in SDCCAG8/BBS16 patients; mesoaxial polydactyly and early renal failure in LZTFL1/BBS17 patients; possible preaxial polydactyly in IFT172/BBS20 patients. Finally, we reported the molecular and clinical description of the largest BBS cohort thanks to the clinical and biological database created in the Laboratory.

Thesis advisor: John Wing / Thesis advisor: Stephen Wicks / Molecular biology and genetics, single nucleotide polymorphism genetic mapping, phenotypic assays including behavioral assessment, and fluorescent microscopy of GFP-tagged proteins were used to study ciliary defects in the nematode Caenorhabditis elegans. Mammalian cilia are multifunctional. Some of the physiological roles in which they are involved include sensing developmental signaling molecules and ligands as well as creating flows of mucus and cerebrospinal fluid that function as flow meters and mechanosensors. Due to the multifunctional nature of cilia, it is not surprising that many human diseases can be caused by ciliary defects. Bardet-Biedl Syndrome is a rare genetic ciliopathy characterized by retinal degeneration, polydactyly, obesity, cystic kidneys, mental retardation, and many other ailments. We have identified osm- 12/bbs-7 to be a C. elegans homologue of human BBS7, a gene known to cause Bardet-Biedl Syndrome when mutated. With the help of Michel Leroux’s group, I showed the BBS-7 protein to be localized to the base of cilia and to undergo intraflagellar transport along the ciliary axoneme. Our findings suggest that BBS- 7 plays a role in the assembly and/or functioning of the IFT complex. I also performed a mutagenesis and phenotypic screen for animals defective in the uptake of DiI into a subset of their ciliated neurons in order to identify new components involved in ciliogenesis and IFT. I describe an extended bulked segregant analysis (BSA) mapping methodology, which can save time and resources by filtering out alleles of previously known genes without performing time-consuming interval mapping. In addition, I identified one of the 11 dyefilling defective alleles from the screen to be a novel allele of dyf-3, which encodes a protein required for sensory cilia formation. / Thesis (PhD) — Boston College, 2008. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

Bardet-Biedl syndrome (BBS) is a rare genetic disease that causes retinal degradation, obesity, kidney dysfunction, polydactyly, and other cilium-related disorders. To date, more than 20 BBS genes, whose mutants cause BBS phenotypes, have been identified, and eight of those (BBS1-2, 4-5, 7-9, and 18) are known to form the BBSome complex. Recent studies have revealed that the BBSome is closely involved in the trafficking of signaling proteins in the primary cilium. Mutations in BBS genes are highly pathogenic because trafficking in the primary cilium is not fully functional when BBS mutations impair assembly of the BBSome. However, the functional links between onset of BBS and BBSome assembly are not well understood. To address this gap in knowledge, we examined the structure of a BBSome assembly intermediate, the BBSome core complex (BBS2, 7, and 9). We employed a combination of chemical crosslinking coupled with mass spectrometry (XL-MS) and electron microscopy (EM) to determine the structure. We applied this structural information to BBS mutations in the core complex to understand how these mutations might cause the disease. These results provide the first structural model of the BBSome core complex and give insight into the molecular basis of Bardet-Biedl syndrome. We have also investigated the mechanism of assembly of the two mTOR kinase complexes (mTORC1 and 2). mTOR is a master regulator of cell metabolism, growth and proliferation. As such, mTOR is a high-value drug target. We investigated the mechanism of assembly of these mTOR complexes and found that the cytosolic chaperonin CCT contributes to mTOR signaling by assisting in the folding of mLST8 and Raptor, components of mTORC1 and mTORC2. To understand the function of CCT in mTOR complex assembly at the molecular level, we have isolated the mLST8-CCT complex and performed a structural analysis using chemical cross-linking couple with mass spectrometry (XL-MS) and cryogenic EM. We found that mLST8 binds CCT deep in its folding cavity, making specific contacts with the CCTα and γ subunits and forming a near-native β-propeller conformation. This information can be used to develop new therapeutics that regulate mTOR activity by controlling mTOR complex assembly.

Bardet Biedl Syndrome (BBS) displays heterogeneity in the genes involved and clinical features. Mutations in 19 genes have been associated with BBS. Eight BBS proteins (BBS1, 2, 4, 5, 7, 8, 9 and 18) form the BBSome. Assembly of the BBSome is mediated by three BBS proteins (BBS6, 10, 12) in a complex with the CCT/Tric chaperonins. The BBSome is involved in formation and maintenance of primary cilia and vesicle trafficking. The clinical features of BBS include obesity, degenerative retinopathy, polydactyly, renal dysfunction, hypogonadism, and learning disability. Diabetes mellitus is commonly associated with BBS, but the mechanisms remain unknown. Our objective was to understand the molecular mechanism of BBS-associated diabetes. The role of BBS in insulin receptor (IR) signaling in Bbs4-/-mice was tested by preventing obesity using calorie restriction. These studies demonstrate the genetic defect in BBS directly contributes to the diabetes phenotype independently from the obesity phenotype. Emerging evidence implicating neuronal mechanisms in various BBS phenotypes led us to test the possibility that loss of Bbs1 in the central nervous system (CNS) disrupts glucose homeostasis. We found that deletion of the Bbs1 gene throughout the CNS or in specific hypothalamic neurons leads to hyperglycemia, glucose intolerance and insulin resistance. Our data demonstrate the critical role of neuronal Bbs1 in the regulation of glucose in an insulin-independent manner. Finally, the IR was found to interact with BBS proteins. The loss of BBSome proteins leads to a specific reduction in the amount of IR at the cell surface. The results demonstrate that BBSome proteins are required to maintain adequate levels of IR at the cell surface. The role of BBS proteins in transporting IR has not been previously described. Loss of the BBSome appears to be a novel mechanism of insulin resistance.

Abstract  In Sweden, moderators of Facebook groups are currently required to remove illegal content from their forums according to BBS-lagen. The law is however old and rarely used, and the impact of it’s existence is unclear. The purpose of the essay is to gain understanding on how moderators of Facebook groups think and act on illegal/inappropriate content that is published within their groups, and what impact the current legislation on the subject in Sweden has on their behavior. In order to examine this the following questions was asked:  -       How does moderators of big Facebook groups reason and act on potentially illegal/inappropriate content in their groups?  -       How do moderators of big Facebook groups reason and act on potentially illegal/inappropriate content in their groups, in relation to the law on bulletin board systems (BBS-lagen)?  The theoretical vantage points were the Public Sphere by Habermas and Panopticon by Foucault, to explain the actions of the moderators and the impact of legislation. The methods used were semi-structured qualitative interviews with moderators of Facebook groups, in combination with an analysis on relevant legal documents.  The study found that the majority of the interviewed Facebook moderators had a semi - rigorous moderation approach, where freedom of speech was important, but also second to the wellbeing of the community. The forums had to have some level of surveillance on a regular basis, often following use of the Facebook report function. They were mostly aware of the legislation but did not actively use it as a tool for moderation, they leaned on the group's internal regulations instead.    Keywords: BBS-lagen, democracy online, surveillance, Facebook moderation, illegal content