The G(1) cyclin Cln3 promotes cell cycle entry via the transcription factor Swi6

In Saccharomyces cerevisiae (budding yeast), commitment to cell division in late G1 is promoted by the G1 cyclin Cln3 and its associated cyclin-dependent kinase, Cdc28. We show here that all known aspects of the function of Cln3 in G1 phase, including control of cell size, pheromone sensitivity, cell cycle progress, and transcription, require the protein Swi6. Swi6 is a component of two related transcription factors, SBF and MBF, which are known to regulate many genes at the G1-S transition. The Cln3-Cdc28 complex somehow activates SBF and MBF, but there was no evidence for direct phosphorylation of SBF/MBF by Cln3-Cdc28 or for a stable complex between SBF/MBF and Cln3-Cdc28. The activation also does not depend on the ability of Cln3 to activate transcription when artificially recruited directly to a promoter. The amino terminus and the leucine zipper of Swi6 are important for the ability of Swi6 to respond to Cln3 but are not essential for the basal transcriptional activity of Swi6. Cln3-Cdc28 may activate SBF and MBF indirectly, perhaps by phosphorylating some intermediary protein

Centralization of pediatric surgical care in the Netherlands:Lessons learned

Centralization of care is a difficult process, as there are several stakeholders that are involved and should be heard. What can be the best option for a small group of patients may be detrimental to a larger group of patients that cannot be adequately treated close to home. The weighing of these factors is different in every environment. One universal rule however is: if you don't do it yourselves, others will do it for you. In the Netherlands, pediatric oncology, including surgery, is centralized in one center (Utrecht) with the help of several shared care centers scattered throughout the country for things that can be managed close to home. (c) 2021 Elsevier Inc. All rights reserved

Fast But Not Furious. When Sped Up Bit Rate of Information Drives Rule Induction

The language abilities of young and adult learners range from memorizing specific items to finding statistical regularities between them (item-bound generalization) and generalizing rules to novel instances (category-based generalization). Both external factors, such as input variability, and internal factors, such as cognitive limitations, have been shown to drive these abilities. However, the exact dynamics between these factors and circumstances under which rule induction emerges remain largely underspecified. Here, we extend our information-theoretic model (Radulescu et al., 2019), based on Shannon’s noisy-channel coding theory, which adds into the “formula” for rule induction the crucial dimension of time: the rate of encoding information by a time-sensitive mechanism. The goal of this study is to test the channel capacity-based hypothesis of our model: if the input entropy per second is higher than the maximum rate of information transmission (bits/second), which is determined by the channel capacity, the encoding method moves gradually from item-bound generalization to a more efficient category-based generalization, so as to avoid exceeding the channel capacity. We ran two artificial grammar experiments with adults, in which we sped up the bit rate of information transmission, crucially not by an arbitrary amount but by a factor calculated using the channel capacity formula on previous data. We found that increased bit rate of information transmission in a repetition-based XXY grammar drove the tendency of learners toward category-based generalization, as predicted by our model. Conversely, we found that increased bit rate of information transmission in complex non-adjacent dependency aXb grammar impeded the item-bound generalization of the specific a_b frames, and led to poorer learning, at least judging by our accuracy assessment method. This finding could show that, since increasing the bit rate of information precipitates a change from item-bound to category-based generalization, it impedes the item-bound generalization of the specific a_b frames, and that it facilitates category-based generalization both for the intervening Xs and possibly for a/b categories. Thus, sped up bit rate does not mean that an unrestrainedly increasing bit rate drives rule induction in any context, or grammar. Rather, it is the specific dynamics between the input entropy and the maximum rate of information transmission

The Role of RUNX2 in Osteosarcoma Oncogenesis

Osteosarcoma is an aggressive but ill-understood cancer of bone that predominantly affects adolescents. Its rarity and biological heterogeneity have limited studies of its molecular basis. In recent years, an important role has emerged for the RUNX2 “platform protein” in osteosarcoma oncogenesis. RUNX proteins are DNA-binding transcription factors that regulate the expression of multiple genes involved in cellular differentiation and cell-cycle progression. RUNX2 is genetically essential for developing bone and osteoblast maturation. Studies of osteosarcoma tumours have revealed that the RUNX2 DNA copy number together with RNA and protein levels are highly elevated in osteosarcoma tumors. The protein is also important for metastatic bone disease of prostate and breast cancers, while RUNX2 may have both tumor suppressive and oncogenic roles in bone morphogenesis. This paper provides a synopsis of the current understanding of the functions of RUNX2 and its potential role in osteosarcoma and suggests directions for future study

Sustainable Performance Optimization for Digital Housing

With natural resources depleting, sustainable solutions are becoming more and more a necessity. To deal with the depleting resources, the Dutch government aims to generate 14% of country’s energy consumption through natural resources by 2020. The Dutch built environment is estimated to be responsible for 38.1% of the total energy consumption. This means that investments and innovation within this area have high potential. However, there are some indications that these goals cannot be met. New houses often meet these requirements but, with a growth of 0.8% per year, these only make up for a small portion of all projects. As a result, a strong focus lays on improving and renovating the existing housing market towards a sustainable and low energy environment. For this transition, information on the current housing market, possible renovation options and insight on the investments costs are required. Within this PDEng-project the aim is to further develop WoonConnect, a digital tool that can help to speed up this transition for both renovation projects and new buildings

Longitudinal Trajectories of Gestational Thyroid Function: A New Approach to Better Understand Changes in Thyroid Function

Context Most studies of thyroid function changes during pregnancy use a cross-sectional design comparing means between groups rather than similarities within groups. Objective Latent class growth analysis (LCGA) is a novel approach to investigate longitudinal changes that provide dynamic understanding of the relationship between thyroid status and advancing pregnancy. Design Prospective observational study with repeated assessments. Setting General community. Patients Eleven hundred healthy women were included at 12 weeks’ gestation. Main Outcome Measures The existence of both free T4 (fT4) and TSH trajectories throughout pregnancy determined by LCGA. Results LCGA revealed three trajectory classes. Class 1 (n = 1019; 92.4%), a low increasing TSH reference group, had a gradual increase in TSH throughout gestation (from 1.1 to 1.3 IU/L). Class 2 (n = 30; 2.8%), a high increasing TSH group, displayed the largest increase in TSH (from 1.9 to 3.3 IU/L). Class 3 (n = 51; 4.6%), a decreasing TSH group, had the largest fall in TSH (from 3.2 to 2.4 IU/L). Subclinical hypothyroidism at 12 weeks occurred in up to 60% of class 3 women and was accompanied by elevated thyroid peroxidase antibodies (TPO-Ab) titers (50%) and a parental history of thyroid dysfunction (23%). In class 2, 70% of women were nulliparous compared with 46% in class 1 and 49% in class 3. Conclusions LCGA revealed distinct trajectories of longitudinal changes in fT4 and TSH levels during pregnancy in 7.4% of women. These trajectories were correlated with parity and TPO-Ab status and followed patterns that might reflect differences in pregnancy-specific immune tolerance between nulliparous and multiparous women