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Exploring a Formula 1 team’s business opportunities within the esports market: An analysis conducted on behalf of Aston Martin Aramco Cognizant Formula 1 Team
No full textDue to a rapidly growing esports scene, new business opportunities are emerging. Using the
example of AMF1, this work addresses a research gap concerning esports market structure and
diverse business opportunities for non-endemic companies. Hence, academic literature and
market research are methodically assessed using Porter's Five Forces and a competitive land scape analysis. A developed esports ecosystem provides a basis to develop potential business
opportunities. Analyzing the stakeholders of the ecosystem and trends, various business opportunities for AMF1 are identified. These are categorized into three commercial commitment levels. Most suitable initiatives for AMF1 are evaluated and demonstrated in a six-year roadmap
To make introsys the top-of-mind company in the industrial automation solutions- industry for new manufactoring segments
No full textIntrosys is a company in the industrial automation solutions’ industry, with 20 years of
experience in the market and it is highly associated with the Automotive industry.
A new target segment for the company was identified in order to diversify its customer
portfolio, diminishing its dependency from the Automotive industry, through a Potential-Risk
Matrix and Market Research.
A complete marketing business plan is then developed to support the company’s entrance in
the new identified market segment in the textile industry, covering marketing strategy,
marketing mix and sales strategy considering company goals and constraints.
Afterwards, an in-depth analysis with a theoretical perspective is conducted for the pricing
strategy. It starts with a reflection about Introsys’ current Pricing Strategy that is followed by a
shift from a Cost-Based approach to a Value-Based strategy. This extensive analysis is an
individual contribute to the group report developed for Introsy
Beyond certification: assessing the domino effect of b corps in the coffee industry
No full textThis study seeks to find out whether the certification of coffee companies inspires other coffee
companies to become B Corp certified too, thereby causing a so-called ‘domino effect’. Using
data which B Lab provided as well as semi-structured interviews, the author finds no evidence
for such a domino effect. However, B Corps, through the changes they implement as a result of
their certification, seem to inspire others - within and outside of their value chain – to improve
their practices. This study thus establishes a new theoretical foundation for B Corp’s impact
through systemic change
Molecular mechanisms of melanosome exocytosis
No full textSkin pigmentation relies on the pigment melanin and ensures photoprotection against ultraviolet
(UV) radiation, avoiding the onset of skin cancers. Melanin is synthesized by melanocytes and stored
within organelles designated melanosomes, which are tethered to actin in melanocyte dendrites
through Rab27a, and finally transferred to keratinocytes. While the molecular players involved in
melanogenesis have been extensively studied, those underlying melanosome exocytosis and
melanin transfer remain unclear. Previously, our group found that Rab11b regulates melanin
secretion and transfer in human skin. Here, we demonstrated that soluble factors, but not
extracellular vesicles, present in keratinocyte-conditioned medium (KCM) stimulate melanin
secretion from melanocytes, and transfer to keratinocytes. Moreover, we found that these factors
are released by differentiated keratinocytes, but not by undifferentiated ones. Importantly, we
ruled out the possibility that KCM increases melanin secretion and transfer as a consequence of
increased melanin synthesis. For this, we quantified intracellular melanin levels in melanocytes
cultured with or without KCM. Additionally, we confirmed that KCM does not increase the
expression of microphthalmia-associated transcription factor (MITF) and its downstream transcript
which encodes for tyrosinase in melanocytes, both required for melanogenesis. We also
demonstrated that Rab3a, but not Rab11b, regulates KCM-stimulated melanin secretion and
transfer, and shows enhanced colocalization with melanosomes in melanocyte dendrites upon
incubation with KCM. Therefore, our results suggest that soluble factors released by differentiated
keratinocytes control skin pigmentation by promoting the accumulation of Rab3a-positive
melanosomes in melanocyte dendrites, and their release and subsequent transfer to keratinocytes.
Furthermore, we found that Rab27a and the Rab3a guanine nucleotide exchange factor (Rab3il1)
regulate KCM-stimulated melanin secretion. We also observed that Ca2+
-dependent signaling
enhances KCM-induced melanin secretion, which raises a possible role for the Ca2+
-dependent
Munc13-2 and Munc18-3 priming proteins in this process. Interestingly, immunoprecipitation and
immunofluorescence assays suggested that Rab3a interacts with Rab27a on melanosome
membranes, in the dendrites of KCM-stimulated melanocytes. Besides the characterization of the
molecular machinery regulating KCM-induced melanin secretion, we identified a soluble factor
present in KCM responsible for the stimulatory effect. Indeed, our results showed that KCM soluble
factor(s) with a molecular weight lower than 3 KDa (< 3 KDa) is (are) the main stimulatory molecules
in melanin secretion. Curiously, NMS-23-01 was abundantly detected in KCM < 3 KDa fraction by
ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)
analysis. Moreover, melanocytes cultured with NMS-23-01 demonstrated a dose-dependent
increase in secreted melanin levels and a decrease in intracellular melanin content. Furthermore,
the incubation of NMS-23-01 in both two-dimensional melanocyte/keratinocyte co-cultures and
three-dimensional reconstructed human pigmented epidermises enhanced melanin transfer and
augmented epidermal pigmentation. Thus, our results identified NMS-23-01 as the first molecule
that increases skin pigmentation by specifically enhancing melanin secretion and subsequent
transfer to keratinocytes. Importantly, NMS-24-01 (a specific antagonist of NMS-23-01) impaired
both NMS-23-01 and KCM-stimulated melanin secretion levels. Additionally, we found that NMS 23-01 and KCM share the same molecular pathway of stimulated melanin secretion, independent
of Rab11b and dependent of Rab27a, Rab3a and Rab3il1. Overall, our results suggest that NMS-23-
01 is at least one of the KCM soluble factors that stimulate melanin secretion. Furthermore, our
studies indicate that two distinct pathways of melanosome exocytosis exist in melanocytes: a basal
pathway controlled by Rab11b and another route controlled by the Rab27a-Rab3il1-Rab3a cascade,
and triggered upon stimulation with NMS-23-01 (and possibly other small keratinocyte-derived
soluble factors). Thus, this study contributed to a better understanding of fundamental processes
of skin pigmentation, namely the molecular players involved in the stimulation of melanin secretion.
Moreover, NMS-23-01 and its antagonist NMS-24-01 were identified in our work as novel and
specific compounds to target melanin secretion and transfer. Therefore, they exhibit the potential
to modulate skin color and serve as the basis of novel therapeutic strategies for
hypo/hyperpigmentation disorders, potentially also with cosmetic applications. Importantly, the
knowledge about NMS-23-01 and the molecular mechanisms stimulating melanin secretion and
transfer can also be applied to stimulate skin tanning and photoprotection against UV-induced DNA
damage.A pigmentação da pele depende do pigmento melanina, que assegura a fotoproteção contra a
radiação ultravioleta (UV), evitando o desenvolvimento de cancros de pele. A melanina é sintetizada
por melanócitos e armazenada em organelos designados melanossomas, que se ligam ao
citoesqueleto de actina nas dendrites dos melanócitos através de Rab27a, sendo posteriormente
transferidos para os queratinócitos. Embora os intervenientes moleculares envolvidos na
melanogénese tenham sido extensivamente estudados, os mecanismos subjacentes à exocitose dos
melanossomas e à transferência de melanina permanecem pouco claros. Anteriormente, o nosso
grupo descobriu que Rab11b regula a secreção e a transferência de melanina na pele humana. Aqui,
demonstramos que fatores solúveis, mas não vesículas extracelulares, presentes no meio
condicionado por queratinócitos (KCM) estimulam a secreção de melanina a partir dos melanócitos
e a sua transferência para os queratinócitos. Além disso, descobrimos que esses fatores são
libertados por queratinócitos diferenciados, mas não pelos não diferenciados. Importa salientar que
descartámos que o KCM aumenta a secreção e a transferência de melanina como consequência de
um aumento da síntese deste pigmento. Para esse propósito, quantificámos os níveis de melanina
intracelular em melanócitos cultivados com ou sem KCM. Confirmámos ainda que o KCM não
aumenta a expressão do fator de transcrição associado à microftalmia (MITF), nem do seu transcrito
que codifica para a tirosinase nos melanócitos, ambos necessários para a melanogénese.
Demonstrámos também que Rab3a, mas não Rab11b, regula a secreção e transferência de melanina
estimulada por KCM, apresentando um aumento da colocalização com os melanossomas nas
dendrites dos melanócitos após incubação com KCM. Portanto, os nossos resultados sugerem que
fatores solúveis libertados por queratinócitos diferenciados controlam a pigmentação da pele,
promovendo a acumulação de melanossomas positivos para Rab3a nas dendrites dos melanócitos,
bem como a sua libertação e subsequente transferência para os queratinócitos. Além disso,
descobrimos que a Rab27a e o fator de troca de nucleotídeos de guanina da Rab3a (Rab3il1),
também regulam a secreção de melanina estimulada por KCM. Observámos igualmente que a
sinalização de Ca2+ potencia a secreção de melanina induzida por KCM e sugerimos uma possível
função neste processo para as proteínas de priming dependentes de Ca2+
, nomeadamente Munc13-
2 e Munc18-3. Curiosamente, os nossos ensaios de imunoprecipitação e imunofluorescência
sugerem que Rab3a e Rab27a interagem na membrana do melanossoma, nas dendrites dos
melanócitos estimulados com KCM. Para além da caracterização da maquinaria molecular que
regula a secreção de melanina induzida por KCM, identificámos um fator solúvel presente neste
meio condicionado responsável por esse efeito estimulatório. Os nossos resultados demonstraram
que o(s) fator(es) solúvel(is) do KCM com um peso molecular inferior a 3 KDa (< 3 KDa) estimula(m)
a secreção de melanina. Curiosamente, a molécula NMS-23-01 foi detetada em abundância no KCM
< 3 KDa através de análise por cromatografia líquida de ultra-alta performance acoplada a
espectrometria de massa tandem (UHPLC-MS/MS). Melanócitos cultivados com NMS-23-01
demonstraram um aumento dependente da dose nos níveis de melanina secretada e uma
diminuição no conteúdo de melanina intracelular. Além disso, a incubação de NMS-23-01 tanto em
coculturas de melanócitos/queratinócitos como em epiderme humana pigmentada reconstruída
aumentou a transferência de melanina e a pigmentação da epiderme. Assim, os nossos resultados
identificaram NMS-23-01 como a primeira molécula que aumenta a pigmentação da pele
especificamente através de um aumento na secreção de melanina e a sua subsequente
transferência para os queratinócitos. Importa salientar que NMS-24-01 (um antagonista específico
de NMS-23-01) inibiu os níveis de secreção de melanina estimulados tanto pela NMS-23-01, como
pelo KCM. Adicionalmente, descobrimos que a NMS-23-01 e o KCM partilham a mesma via
molecular de secreção de melanina, independente de Rab11b e dependente de Rab27a, Rab3a e
Rab3il1. No geral, os nossos resultados sugerem que a NMS-23-01 é, pelo menos, um dos fatores
solúveis presentes no KCM que estimulam a secreção de melanina. Os nossos resultados também
indicam que existem duas vias distintas de exocitose de melanossomas nos melanócitos: uma via
basal controlada por Rab11b e outra via controlada pela cascata Rab27a-Rab3il1-Rab3a, que é
desencadeada sob estimulação com NMS-23-01 (e possivelmente por outros pequenos fatores
solúveis derivados dos queratinócitos). Assim, este estudo contribuiu para uma melhor
compreensão dos processos fundamentais da pigmentação cutânea, nomeadamente dos
intervenientes moleculares envolvidos na estimulação da secreção de melanina. Além disso, NMS 23-01 e o seu antagonista NMS-24-01 foram identificados no nosso trabalho como compostos
inovadores e específicos para regular a secreção e transferência de melanina. Portanto, podem
eventualmente ser utilizados para modular a cor da pele e servir como base para novas estratégias
terapêuticas para doenças de hipo/hiperpigmentação, tendo também possíveis aplicações
cosméticas. É importante destacar que o conhecimento sobre NMS-23-01 e os mecanismos
moleculares que estimulam a secreção e transferência de melanina pode ser também aplicado para
promover o bronzeamento da pele e a fotoproteção contra danos no DNA induzidos pela radiação
U
Uncovering and engineering vitamins B1 and B2 pathways
No full text"Ensuring a sufficient, nutri ous and accessible food supply remains a significant
challenge, in par cular in low and middle income countries. Although widely
cul vated crops, such as rice, provide enough calories, they lack sufficient levels
of essen al micronutrients, nega vely impac ng health, compromising social and
economic progress. Biofor fica on through metabolic engineering of staple crops
offers a cost-effec ve solu on to deliver essen al minerals and vitamins to
popula ons with limited access to diverse diets.(...)"Research Foundation Flanders (FWO;G064119N), Ghent University (Bijzonder Onderzoeksfonds (BOF) GOA
01G00409 and BOF-BAS) and Horizon2020-ERA-NET (BIOFAIR project)
Breaking BIN1 : investigating mechanisms of synaptic dysfunction in Alzheimer’s disease
No full textAbstract
Amyloid-β (Aβ) production is one of the earliest pathological alterations in the
Alzheimer’s disease (AD) patients’ brain and has been the primary focus of therapeutic
research. Yet, synapse loss best correlates with cognitive decline in AD; therefore,
identifying the mechanisms driving synapse dysfunction should become a major
therapeutic target.
BIN1, an endocytic regulator and a significant risk gene for in late-onset AD
(LOAD), has an unclear synaptic role. Our previous studies linked Bin1 to the endocytic
recycling of BACE1, thereby leading to BACE1 accumulation and increased Aβ42
production. We have shown that mutations in Bin1 associated with LOAD, rs754834233
(PL) and rs138047593 (KR), lead to Bin1 loss of function in amyloidogenesis.
However, Bin1’s synaptic function is ill-defined, with evidence suggesting roles at
both presynaptic and postsynaptic sites that could affect synaptic transmission. Indeed,
two previous studies suggest that Bin1 regulates the synaptic vesicle (SV) cycle,
especially during SV release. After SV release, SV endocytic recycling involves
compensatory endocytosis and SV reformation from an intermediate endosomal
compartment, which requires scission and may depend on Bin1 activity. Moreover, we
hypothesized that this function might be disrupted by the LOAD mutations, leading to
synapse dysfunction.
In this study, we assessed Bin1 function in inhibitory and excitatory synapses in
primary mouse cortical neuron cultures. We found that Bin1 localizes presynaptically and
has a crucial role in inhibitory synapses by regulating the SV exocytosis and endocytosis.
Bin1 knockdown reduced synaptic endosome size in inhibitory neurons, likely by
increasing SV exocytosis and endocytosis. In contrast, Bin1 knockdown only reduced
exocytosis in excitatory neurons. Interestingly, inhibitory synapse loss was not rescued
by the LOAD-associated Bin1 mutants or Aβ inhibition. Our results support that Bin1 loss
of function may disrupt synapses prior to Aβ-dependent synapse dysfunction.
Using immunoprecipitation coupled with mass spectrometry-based proteomic
analysis, we found that the LOAD mutations disrupted Bin1 interactions, particularly with
partners related to the SV cycle, actin dynamics, and intracellular trafficking. Using coimmunoprecipitation
and proximity ligation assay, we confirmed that Bin1 mutants
exhibited reduced interaction with regulators of SV cycle, VAMP2, SV2, dynamin, clathrin,
and synaptojanin-1. Notably, clathrin overexpression restored GABAergic synapse
density in Bin1 knockdown neurons, underscoring Bin1’s crucial role in the clathrin-mediated SV cycle.
Bin1 knockdown increased neuronal hyperexcitability, likely due to the loss of
inhibitory synapse function. This effect was mitigated by the antiepileptic levetiracetam,
suggesting that Bin1 risk variants may lower the threshold for the development of
seizures and contribute to AD development. Collectively, these findings suggest that the
Bin1 mutation’s main impact is on the regulation of inhibitory synapse function, possibly
contributing to the synaptic defects observed in Alzheimer’s disease.Resumo
A produção de amiloide-β (Aβ) é uma das alterações patológicas mais precoces no
cérebro de pacientes com doença de Alzheimer e tem sido o principal foco de
investigação terapêutica. No entanto, a perda de sinapses correlaciona-se melhor com o
declínio cognitivo na doença de Alzheimer; portanto, identificar os mecanismos que
impulsionam a disfunção sináptica deve tornar-se um importante alvo terapêutico.
BIN1, um regulador endocítico e um gene de risco significativo para Alzheimer de
início tardio, tem um papel sináptico pouco claro. Os nossos estudos anteriores
implicaram o Bin1 na reciclagem endocítica de BACE1, levando à acumulação de BACE1
e ao aumento da produção de Aβ42. Demonstrámos que mutações no Bin1 associadas
à Alzheimer de início tardio, rs754834233 (PL) e rs138047593 (KR), levam à perda de
função do Bin1 na amiloidogénese.
No entanto, a função sináptica do Bin1 está mal definida, com alguma evidência
de função nos compartimentos pré-sináptico, mas também no pós-sináptico que
podem afetar a transmissão sináptica. De facto, os primeiros estudos sugeriam que o
Bin1 regula o ciclo das vesículas sinápticas, especialmente na libertação das vesículas.
Após a exocitose, a reciclagem endocítica das vesículas sinápticas envolve endocitose
compensatória e reconstituição das vesículas a partir de um endossoma intermediário,
o que requer sisão que pode depender da atividade do Bin1. Além disso, propomos a
hipótese que essa função pode ser perturbada pelas mutações no Bin1, levando à
disfunção sináptica.
Neste estudo, avaliámos a função do Bin1 nas sinapses inibitórias e excitatórias em
culturas primárias de neurónios corticais de ratinho. Descobrimos que o Bin1 se localiza
pré-sinapticamente e tem um papel crucial nas sinapses inibitórias, regulando a
exocitose e a endocitose de vesiculas sinápticas. A redução do Bin1 diminuiu o tamanho
dos endossomas sinápticos em neurónios inibitórios, provavelmente pelo aumento da
exocitose e a endocitose. Em contraste, quando diminuída a sua expressão Bin1 apenas
reduziu a exocitose em neurónios excitatórios. Curiosamente, os mutantes de Bin1
associados a Alzheimer de início tardio não recuperaram a perda de sinapses inibitórias,
e sendo esta perda insensível à inibição de Aβ. Os nossos resultados suportam que a
perda de função do Bin1 pode prejudicar as sinapses antes de Aβ.
Usando imunoprecipitação acoplada à análise proteómica baseada em
espectrometria de massa, descobrimos que as mutações no Bin1 perturbam o seu
interatoma, particularmente relacionado com o ciclo das vesículas sinápticas, dinâmica de actina e tráfego intracelular. Usando co-imunoprecipitação e ensaio de ligação por
proximidade, confirmámos que os mutantes do Bin1 apresentaram interação reduzida
com VAMP2, SV2, dinamina, clatrina e sinaptojanina-1. Notavelmente, a sobrerexpressão
de clatrina restaurou a densidade de sinapses GABAérgicas em neurónios com
expressão reduzida de Bin1, ressaltando o papel crucial do Bin1 na reciclagem de
vesiculas sinápticas mediada por clatrina.
A redução do Bin1 aumentou a hiperexcitabilidade neuronal, provavelmente
devido à perda de sinapses inibitórias. Este efeito foi mitigado pelo antiepilético
levetiracetam. Concluímos que as que variantes de risco do Bin1 podem diminuir o limiar
para o desenvolvimento de convulsões e contribuir para o desenvolvimento da doença
de Alzheimer. Coletivamente, descobrimos que as mutações no Bin1 prejudicam a sua
capacidade de regular a função sináptica inibitória, potencialmente contribuindo para
os defeitos sinápticos observados na doença de Alzheimer
To make introsys the top-of-mind company in the industrial automation solutions- industry for new manufacturing segments - exploring introsys- segmentation, targeting and oositioning strategy for new segment entry
No full textIntrosys is a company in the industrial automation solutions’ industry, with 20 years of
experience in the market and it is highly associated with the Automotive industry.
A new target segment for the company was identified in order to diversify its customer
portfolio, diminishing its dependency from the Automotive industry, through a Potential-Risk
Matrix and Market Research.
A complete marketing business plan is then developed to support the company’s entrance in
the new identified market segment in the textile industry, covering marketing strategy,
marketing mix and sales strategy considering company goals and constraints.
Afterwards, an in-depth analysis with a theoretical perspective is conducted for segmentation,
targeting, and positioning as an individual contribution to the group report
Exploring a Formula 1 team’s business opportunities within the esports market - conducting a Porter's Five Forces and Competitive Landscape Analysis
No full textDue to a rapidly growing esports scene, new business opportunities are emerging. Using the
example of AMF1, this work addresses a research gap concerning esports market structure and
diverse business opportunities for non-endemic companies. Hence, academic literature and
market research are methodically assessed using Porter's Five Forces and a competitive land scape analysis. A developed esports ecosystem provides a basis to develop potential business
opportunities. Analyzing the stakeholders of the ecosystem and trends, various business opportunities for AMF1 are identified. These are categorized into three commercial commitment levels. Most suitable initiatives for AMF1 are evaluated and demonstrated in a six-year roadmap
Sustainability reporting software in the scope of CSRD: design of an application prototype for environmental CSRD assessment
No full textThis thesis explores the development of sustainability reporting software, with a focus on the
Corporate Sustainability Reporting Directive (CSRD). It comprehensively evaluates existing
software solutions, examining their key features and assessing their alignment with CSRD
standards. Incorporating expert interviews and competitor analysis, the study uncovers existing
gaps and potential future advancements in the field. Building on this a software prototype based on
ESRS is developed to provide a possible reporting software solution for companies. The results
from this process are critically discussed and recommendations for future research and
development are derived from it
Influence of corporate social responsibility on brand image, perceived quality, and consumer purchase intention in the German skincare market
No full textThis study examines the influence of Corporate Social Responsibility (CSR) on brand image,
perceived quality, and consumer purchase intention in the German skincare market. Through
quantitative research, findings show that while CSR positively influences brand image and
perceived quality, it does not significantly affect consumer purchase intention directly.
However, CSR has a mediating effect on brand image and perceived quality, significantly
increasing consumer purchase intention. The study highlights the importance of transparent
communication of CSR activities to enhance brand image, perceived quality, and consumer
purchase intention. These insights provide actionable recommendations for skincare brands to
integrate CSR initiatives into their marketing strategies effectively