Linguistic Autonomy of EU Institutions, Bodies and Agencies

This article aims at shedding some light on both explicit and implicit internal language arrangements and practices which currently exist in the various EU institutions, bodies and agencies. It will be shown that they enjoy in effect a large “linguistic autonomy” to determine their own internal language arrangements. The legal basis of this linguistic autonomy will be discussed, as well as the ensuing internal language policies which have been explicitly or implicitly established

Challenges and possible clinical applications of human embryonic stem cell research

Human embryonic stem cells (hESC) are harvested from the inner cell mass of the pre-implantation embryo and possess several unique characteristics. First, they are self-renewing, meaning they can grow indefinitely in an appropriate culture environment and secondly, they are pluripotent, which means they have the potential to become nearly every cell of the human body. Consequently, hESC offer a unique insight into basic human development in vitro, allow better understanding of the genetic and molecular controls of these processes, and are of pharmaceutical interest to test or develop new drugs. The most exciting and high-profile potential application of hESC research is the possibility that such cells can be used for regenerative medicine. Still, several obstacles have to be overcome before clinical applications can be considered: (i) xeno-free derivation and culture of hESC is necessary; (ii) hESC should be safe after transplantation and (iii) their identity and behaviour should be well-known

Treatment of human embryos with the TGFβ inhibitor SB431542 increases epiblast proliferation and permits successful human embryonic stem cell derivation

C

Drug resistance and new therapies in colorectal cancer

Colorectal cancer (CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo- and targeted therapies provide only a limited increase of overall survival for these patients. The major reason for clinical outcome finds its origin in therapy resistance. Escape mechanisms to both chemo- and targeted therapy remain the main culprits. Here, we evaluate major resistant mechanisms and elaborate on potential new therapies. Amongst promising therapies is α-amanitin antibody-drug conjugate targeting hemizygous p53 loss. It becomes clear that a dynamic interaction with the tumor microenvironment exists and that this dictates therapeutic outcome. In addition, CRC displays a limited response to checkpoint inhibitors, as only a minority of patients with microsatellite instable high tumors is susceptible. In this review, we highlight new developments with clinical potentials to augment responses to checkpoint inhibitors

Childhood abuse and adult sociocognitive skills : distinguishing between self and other following early trauma

Experience of childhood abuse (CA) impairs complex social functioning in children; however, much less is known about its effects on basic sociocognitive processes and even fewer studies have investigated these in adult survivors. Using two behavioral tasks, this study investigated spontaneous theory of mind (ToM) and imitative behavior in 41 women with CA and 26 unaffected comparison (UC) women. In the spontaneous ToM task, UCs showed a larger ToM index than CAs, indicating more facilitation by knowledge of another's false belief. In the imitation-inhibition task, CAs experienced less interference than UCs when observing another's incongruent movements. After controlling for depression, differences in ToM became marginally significant, yet remained highly significant for inhibiting imitative behavior. The findings suggest CA survivors have altered perspective-taking and are less influenced by others' perspectives, potentially due to changes in self-other distinction. Clinical implications regarding therapeutic practice with survivors of CA are discussed

Targeting the tumor microenvironment to enhance antitumor immune responses

The identification of tumor-specific antigens and the immune responses directed against them has instigated the development of therapies to enhance antitumor immune responses. Most of these cancer immunotherapies are administered systemically rather than directly to tumors. Nonetheless, numerous studies have demonstrated that intratumoral therapy is an attractive approach, both for immunization and immunomodulation purposes. Injection, recruitment and/or activation of antigen-presenting cells in the tumor nest have been extensively studied as strategies to cross-prime immune responses. Moreover, delivery of stimulatory cytokines, blockade of inhibitory cytokines and immune checkpoint blockade have been explored to restore immunological fitness at the tumor site. These tumor-targeted therapies have the potential to induce systemic immunity without the toxicity that is often associated with systemic treatments. We review the most promising intratumoral immunotherapies, how these affect systemic antitumor immunity such that disseminated tumor cells are eliminated, and which approaches have been proven successful in animal models and patients

CRISPR/Cas9-mediated genome editing in naïve human embryonic stem cells

The combination of genome-edited human embryonic stem cells (hESCs) and subsequent neural differentiation is a powerful tool to study neurodevelopmental disorders. Since the naive state of pluripotency has favourable characteristics for efficient genome-editing, we optimized a workflow for the CRISPR/Cas9 system in these naive stem cells. Editing efficiencies of respectively 1.3-8.4% and 3.819% were generated with the Cas9 nuclease and the D10A Cas9 nickase mutant. Next to this, wildtype and genome-edited naive hESCs were successfully differentiated to neural progenitor cells. As a proofof- principle of our workflow, two monoclonal genome-edited naive hESCs colonies were obtained for TUNA, a long non-coding RNA involved in pluripotency and neural differentiation. In these genome-edited hESCs, an effect was seen on expression of TUNA, although not on neural differentiation potential. In conclusion, we optimized a genome-editing workflow in naive hESCs that can be used to study candidate genes involved in neural differentiation and/or functioning