[The Importance of Attachment for Human Beings and Dogs - Implications for Dog-Assisted Psychotherapy]. / Die Bedeutung von Bindung bei Mensch und Hund ­ Implikationen für die hundegestützte Psychotherapie.

Attachment theory is known as an important therapeutic foundation. Establishing a secure attachment to a caregiver is equally relevant for the mental health of both humans and dogs. A bond can be formed between humans and dogs that is comparable to the attachment between mother and child. Patients with adverse attachment experiences often struggle to maintain stable relationships due to internal working models. Building a therapeutic alliance can also be challenging. On the other hand, establishing a relationship with a dog seems to be successful for patients with adverse attachment experiences. Inclusion of a therapy dog provides them with the opportunity for experiences of trustful relationships.These experiences can then be transferred to the therapist. Later on, internal working models of the patients can indeed come into play in the relationship with the dog. The resulting patterns of relationship can become visible in the interaction with the dog. Within the therapeutic triade of patient, therapy dog and therapist, these patterns can be reflected and integrated into the therapy process. However, achieving this requires a targeted and professionally grounded use of the dog. If dogs are employed with a therapeutic purpose but without professional guidance, there is a risk of reestablishing insecure attachment patterns, which could potentially lead to more disadvantages than benefits for both humans and dogs.

Optimizing Dosage-Specific Treatments in a Multi-Scale Model of a Tumor Growth.

The emergence of cell resistance in cancer treatment is a complex phenomenon that emerges from the interplay of processes that occur at different scales. For instance, molecular mechanisms and population-level dynamics such as competition and cell-cell variability have been described as playing a key role in the emergence and evolution of cell resistances. Multi-scale models are a useful tool for studying biology at very different times and spatial scales, as they can integrate different processes occurring at the molecular, cellular, and intercellular levels. In the present work, we use an extended hybrid multi-scale model of 3T3 fibroblast spheroid to perform a deep exploration of the parameter space of effective treatment strategies based on TNF pulses. To explore the parameter space of effective treatments in different scenarios and conditions, we have developed an HPC-optimized model exploration workflow based on EMEWS. We first studied the effect of the cells' spatial distribution in the values of the treatment parameters by optimizing the supply strategies in 2D monolayers and 3D spheroids of different sizes. We later study the robustness of the effective treatments when heterogeneous populations of cells are considered. We found that our model exploration workflow can find effective treatments in all the studied conditions. Our results show that cells' spatial geometry and population variability should be considered when optimizing treatment strategies in order to find robust parameter sets.

BET Proteins Regulate Expression of Osr1 in Early Kidney Development.

In utero renal development is subject to maternal metabolic and environmental influences affecting long-term renal function and the risk of developing chronic kidney failure and cardiovascular disease. Epigenetic processes have been implicated in the orchestration of renal development and prenatal programming of nephron number. However, the role of many epigenetic modifiers for kidney development is still unclear. Bromodomain and extra-terminal domain (BET) proteins act as histone acetylation reader molecules and promote gene transcription. BET family members Brd2, Brd3 and Brd4 are expressed in the nephrogenic zone during kidney development. Here, the effect of the BET inhibitor JQ1 on renal development is evaluated. Inhibition of BET proteins via JQ1 leads to reduced growth of metanephric kidney cultures, loss of the nephron progenitor cell population, and premature and disturbed nephron differentiation. Gene expression of key nephron progenitor transcription factor Osr1 is downregulated after 24 h BET inhibition, while Lhx1 and Pax8 expression is increased. Mining of BRD4 ChIP-seq and gene expression data identify Osr1 as a key factor regulated by BRD4-controlled gene activation. Inhibition of BRD4 by BET inhibitor JQ1 leads to downregulation of Osr1, thereby causing a disturbance in the balance of nephron progenitor cell self-renewal and premature differentiation of the nephron, which ultimately leads to kidney hypoplasia and disturbed nephron development. This raises questions about the potential teratogenic effects of BET inhibitors for embryonic development. In summary, our work highlights the role of BET proteins for prenatal programming of nephrogenesis and identifies Osr1 as a potential target of BET proteins.