Purpose of Review Novel 3D organoid culture techniques have enabled long-term expansion of pancreatic tissue. This review comprehensively summarizes and evaluates the applications of primary tissue... Show morePurpose of Review Novel 3D organoid culture techniques have enabled long-term expansion of pancreatic tissue. This review comprehensively summarizes and evaluates the applications of primary tissue-derived pancreatic organoids in regenerative studies, disease modelling, and personalized medicine.Recent Findings Organoids derived from human fetal and adult pancreatic tissue have been used to study pancreas development and repair. Generated adult human pancreatic organoids harbor the capacity for clonal expansion and endocrine cell formation. In addition, organoids have been generated from human pancreatic ductal adenocarcinoma in order to study tumor behavior and assess drug responses.Summary Pancreatic organoids constitute an important translational bridge between in vitro and in vivo models, enhancing our understanding of pancreatic cell biology. Current applications for pancreatic organoid technology include studies on tissue regeneration, disease modelling, and drug screening. Show less
Several studies have highlighted the uniqueness of the human immune system in early life. Due to the scarceness of human fetal tissues and technical limitations, a system-wide and detailed... Show moreSeveral studies have highlighted the uniqueness of the human immune system in early life. Due to the scarceness of human fetal tissues and technical limitations, a system-wide and detailed phenotypical characterization of the composition and development of the human fetal immune system was lacking. Here, I delineate the composition and development of the human fetal immune system using an array of advanced high-throughput technologies. First, mass cytometry analysis of the innate lymphoid cells revealed a previously unrecognized subset named int-ILC in the fetal intestine, which can give rise to NK cells and ILC3s. Moreover, by combining the acquired datasets from (imaging-) mass cytometry, single-cell RNA-sequencing and TCR sequencing with advanced computational analysis tools and functional analysis this revealed that memory-like CD4+ T cells were already generated in the developing human fetal intestine, indicative of in utero exposure to foreign antigens. Additionally, (imaging-) mass cytometry analysis of the immune cells in the fetal intestine, spleen and liver revealed an early-life immune compartmentalization in these different fetal tissues. Overall, our results deepens the understanding of prenatal immunity and may ultimately be useful for the development of “early” intervention strategies to prevent the development of immune mediated diseases later in life. Show less
The workshop touched upon a multitude of topics. These can be subsumed under the following main headers:It included methodological considerations around doing comparative law and combining methods... Show moreThe workshop touched upon a multitude of topics. These can be subsumed under the following main headers:It included methodological considerations around doing comparative law and combining methods of comparative law with methods from other fields such as history, political science, sociology, computer science and accounting research.Empirically, it focused on understanding how a transplant process actually works and why it takes place, i.e. who the actors are that make a transplant happen. This included meso-level perspectives, focusing on actors such as bureaucracies, experts, lawmakers, companies, accounting firms and others, but also perspectives which focused more on states as a whole and their role as norm makers and takers. The analyses thereby drew from experiences from many different countries around the world and included a number of historical perspectives as well. The participants also discussed evidence on the extent to which convergence is occurring, using the example of the tax treaty system and the implementation of the BEPS standards.Theoretically, several key concepts were discussed such as the notion of “expertise”, “international standard”, the concept of “transplant” itself and possible alternative metaphors as well as the history of the idea. It was also examined how one can approach the empirical fact of transplants or international convergence of rules from a normative and philosophical point of view.This document reports the discussions that took place during the five days in a chronological manner. The last section contains an outline of possible topics and approaches for a follow-up workshop.The report does not systematically differentiate between individual opinions that not everyone might share and consensus. It rather reports which bits and pieces of the debates caught the attention of the reporters and other note takers. It may therefore rather be seen as something stimulating further discussion than a fixed document. Show less
A key process in the life of any multicellular organism is its development from a single egg into a full grown adult. The first step in this process often consists of forming a tissue layer out of... Show moreA key process in the life of any multicellular organism is its development from a single egg into a full grown adult. The first step in this process often consists of forming a tissue layer out of randomly placed cells on the surface of the egg. We present a model for generating such a tissue, based on mechanical interactions between the cells, and find that the resulting cellular pattern corresponds to the Voronoi tessellation of the nuclei of the cells. Experimentally, we obtain the same result in both fruit flies and flour beetles, with a distribution of cell shapes that matches that of the model, without any adjustable parameters. Finally, we show that this pattern is broken when the cells grow at different rates. Show less
Constructing a knowledge representation from multiple texts requires the integration of information across texts. The aim of the current study was to investigate how elementary school students... Show moreConstructing a knowledge representation from multiple texts requires the integration of information across texts. The aim of the current study was to investigate how elementary school students integrate information across multiple text passages and, particularly, whether students use information from a prior text to improve understanding of a current text. A sample of 105 children in grades 4 and 6 participated in the experiment. The multiple-text integration paradigm was used to study integration processes across texts during reading. Recall and (application) questions were used to investigate the extent to which information from different text passages was integrated into knowledge representations after reading. Individual differences in reading comprehension ability and working memory were also considered. The results indicate that children in both grades spontaneously activate information from an earlier text to aid their understanding during reading, and that they integrate information across texts in their knowledge representations. This was the case regardless of grade or individual differences in reading-comprehension ability and working memory. These findings provide insight into the mechanisms that may be involved in the integration of information across texts. Show less
Many hunter-gatherer groups live on the outskirts of wider society, experiencing poor health outcomes with little access to medical care. From a development perspective, key interventions include... Show moreMany hunter-gatherer groups live on the outskirts of wider society, experiencing poor health outcomes with little access to medical care. From a development perspective, key interventions include the sedentarisation of these mobile peoples into camps nearby larger towns with sanitation infrastructure and medical care, as increased access to services is assumed to improve outcomes. However, recent research in the Agta (Philippine foragers from North-east Luzon) has demonstrated that individuals residing in more ‘developed’ communities suffer from increased morbidity and mortality. Here, using quantitative and ethnographic data on health collected between 2002 and 2014, we explore why this trend occurs by examining the relationship between key development initiatives with self-reported illness and the uptake of medical interventions with 415 Agta men, women and children. We demonstrate that health outcomes worsen as sedentarisation progresses, despite some increases in medical access. We argue this is because the development paradigm is not evidence-based, but rather stems from an ideological dislike of mobile hunter-gatherer lifestyles. Compounded by cultural insensitivity and daily discrimination, current interventions are ill-suited to the unique needs of hunter-gatherers, and thus ineffective. Based on our findings we offer future short and long-term policy suggestions which seek to reduce the Agta's vulnerability, rather than increase it. Show less
In this thesis we aimed to get insight in how the methylome is established during development and subsequently degenerates during ageing using an integrative approach to the analysis of DNA... Show moreIn this thesis we aimed to get insight in how the methylome is established during development and subsequently degenerates during ageing using an integrative approach to the analysis of DNA methylation in conjunction with other levels of genomics data. The first two empirical chapters of this thesis describe the establishment and the maintenance of the epigenome during fetal development and in later life in multiple tissues. In the subsequent two chapters we investigated the loss of control over the methylome in blood and other tissues. Show less
ABSTRACT In reflection upon the worthy work of Professor Shinya Konaka and his col- leagues, this contribution discusses the idea of “Localization of Humanitarian Assistance”. Several critical... Show moreABSTRACT In reflection upon the worthy work of Professor Shinya Konaka and his col- leagues, this contribution discusses the idea of “Localization of Humanitarian Assistance”. Several critical questions arise from a humanitarian situation where the needs are assessed: we have to know what people need and what they don’t need. We need to determine coping mech- anisms that need not substituted but rather facilitated. To not undermine and further marginal- ize we need to know what resources, skills and social capital East African pastoralists have and how they are activated, where and when. The discussion is organized in observations from on one hand, archaeological and heritage perspective and on the other, personal experience of refugees and IDP life in the East Africa. It concludes that people do not only need food and shelter to survive and that cultural heritage is a basic human need too. Without the traditional skills and coping mechanisms that are inherent in the cultural values that glue people together, it is difficult for East African pastoralists to survive. Violence and neglect against people and environment are related to the destruction and neglect of cultural and natural heritage, which are people’s means of livelihood and sources of identity and dignity. Show less
Gurp, L. van; Loomans, C.J.M.; Krieken, P.P. van; Dharmadhikari, G.; Jansen, E.; Ringnalda, F.C.A.S.; ... ; Koning, E.J.P. de 2016
International nongovernmental organizations (INGOs) provide essential aid and public services to less-developed countries. Although most literature focuses on Western INGOs, Asian INGOs have also... Show moreInternational nongovernmental organizations (INGOs) provide essential aid and public services to less-developed countries. Although most literature focuses on Western INGOs, Asian INGOs have also become globally active. Little is known about what motivates INGOs to provide services in other regions, such as Latin America. In this study, we seek to identify the criteria Japanese INGOs use to select Latin American recipient countries. We propose that Japanese INGO operational location decisions are a function of Japanese foreign policy agenda, Japan-recipient country business relations, and recipient country’s need and liberalization. Using data from Japanese INGOs working in Latin America and 24 Latin American countries on contextual, macroeconomic, and demographic indicators, we find that the significant factors driving INGO decisions to operate in Latin American countries are need and the presence of Japanese businesses in the recipient country. Results have practical implications for foreign aid targeting and economic development. Show less
This book is about the creation and enforcement of labour law in Indonesia, a topic that reflects the broader processes of social and political change in the country. Its starting point is... Show more This book is about the creation and enforcement of labour law in Indonesia, a topic that reflects the broader processes of social and political change in the country. Its starting point is the notion of the trade union as a crucial institution in any modern industrial capitalist society, with the potential of promoting some measure of equity and social justice in society. The book discusses three case-studies relating to three major pieces of labour legislation enacted since the Reformasi of 1998 in Indonesia. The first is about trade union legislation, the second about minimum wage policy, and the third about the Industrial Relations Court. These cases show how labour law in Indonesia is best understood as the result of the struggles between different social groups and competing ideologies, which change over time. The author argues that despite all the problems and challenges there remains hope for the development of a sound and effective labour law in Indonesia. This is due in particular to the development of the trade union movement in the country. Unions form a countervailing power against capital and corporate power, and may thus ensure that the results of development are redistributed fairly throughout society. They are also agents of education: their efforts to develop new labour laws and enforce labour standards make workers aware of their rights and may even help in developing a higher degree of rights-consciousness in society more generally. This book is about the creation and enforcement of labour law in Indonesia, a topic that reflects the broader processes of social and political change in the country. Its starting point is the notion of the trade union as a crucial institution in any modern industrial capitalist society, with the potential of promoting some measure of equity and social justice in society. The book discusses three case-studies relating to three major pieces of labour legislation enacted since the Reformasi of 1998 in Indonesia. The first is about trade union legislation, the second about minimum wage policy, and the third about the Industrial Relations Court. These cases show how labour law in Indonesia is best understood as the result of the struggles between different social groups and competing ideologies, which change over time. The author argues that despite all the problems and challenges there remains hope for the development of a sound and effective labour law in Indonesia. This is due in particular to the development of the trade union movement in the country. Unions form a countervailing power against capital and corporate power, and may thus ensure that the results of development are redistributed fairly throughout society. They are also agents of education: their efforts to develop new labour laws and enforce labour standards make workers aware of their rights and may even help in developing a higher degree of rights-consciousness in society more generally. Show less
Primordial germ cells (PGCs) are the progenitors of the gametes, responsible for transmitting genetic information from generation to generation. Although there is a long history of gamete biology... Show morePrimordial germ cells (PGCs) are the progenitors of the gametes, responsible for transmitting genetic information from generation to generation. Although there is a long history of gamete biology research, there is still a lot to be learned about many of the mechanisms underlying germ cell development. This dissertation describes and discusses the dynamics of PGCs in the chicken, with a focus on their migration to the gonads and meiosis that takes place when PGCs are already settled there. We also discussed the advantages of using the avian model in epithelial ovarian cancer research. Moreover, we revisited an often overlooked model for amniogenesis in which the proamnion plays a crucial role. Show less
The embryonic development of the human cochlea (the organ of hearing) has been investigated for over one hundred years. However, little is still known about the development on a cellular and... Show moreThe embryonic development of the human cochlea (the organ of hearing) has been investigated for over one hundred years. However, little is still known about the development on a cellular and protein level, which is important to better understand etiologies and pathologies of various types of sensorineural hearing loss. Knowledge of the normal gene expression patterns and cell fate specification in the human cochlea has therefore the potential to aid in the development of gene and cell-based therapeutic strategies. For this reason, we acquired a series of human fetal cochlea of different stages of gestation and investigated several aspects of the normal development of the human cochlea such as the hair cells, the spiral ganglion neurons and the stria vascularis. Also, we investigated the neural crest stem cells residing in the hair follicle bulge. We showed that a protein (TUBB3) often used in immunochemistry to detect a neuron is also expressed both in skin and hair follicle melanocytes in humans meaning that the proposed neural crest stem cell residing in the hair follicle bulge might need revision. Show less
