Overview of the PALM model system 6.0

In this paper, we describe the PALM model system 6.0. PALM (formerly an abbreviation for Parallelized Largeeddy Simulation Model and now an independent name) is a Fortran-based code and has been applied for studying a variety of atmospheric and oceanic boundary layers for about 20 years. The model is optimized for use on massively parallel computer architectures. This is a follow-up paper to the PALM 4.0 model description in Maronga et al. (2015). During the last years, PALM has been significantly improved and now offers a variety of new components. In particular, much effort was made to enhance the model with components needed for applications in urban environments, like fully interactive land surface and radiation schemes, chemistry, and an indoor model. This paper serves as an overview paper of the PALM 6.0 model system and we describe its current model core. The individual components for urban applications, case studies, validation runs, and issues with suitable input data are presented and discussed in a series of companion papers in this special issue

Co-chaperones are limiting in a depleted chaperone network

To probe the limiting nodes in the chaperoning network which maintains cellular proteostasis, we expressed a dominant negative mutant of heat shock factor 1 (dnHSF1), the regulator of the cytoplasmic proteotoxic stress response. Microarray analysis of non-stressed dnHSF1 cells showed a two- or more fold decrease in the transcript level of 10 genes, amongst which are the (co-)chaperone genes HSP90AA1, HSPA6, DNAJB1 and HSPB1. Glucocorticoid signaling, which requires the Hsp70 and the Hsp90 folding machines, was severely impaired by dnHSF1, but fully rescued by expression of DNAJA1 or DNAJB1, and partially by ST13. Expression of DNAJB6, DNAJB8, HSPA1A, HSPB1, HSPB8, or STIP1 had no effect while HSP90AA1 even inhibited. PTGES3 (p23) inhibited only in control cells. Our results suggest that the DNAJ co-chaperones in particular become limiting in a depleted chaperoning network. Our results also suggest a difference between the transcriptomes of cells lacking HSF1 and cells expressing dnHSF1

Keeping cells healthy : using the chaperone network : a look inside the cellular toolbox

Contains fulltext : 93561.pdf (publisher's version ) (Open Access)Radboud Universiteit Nijmegen, 29 juni 2012Promotor : Lubsen, N.H.203 p

A delayed antioxidant response in heat-stressed cells expressing a non-DNA binding HSF1 mutant

To assess the consequences of inactivation of heat shock factor 1 (HSF1) during aging, we analyzed the effect of HSF1 K80Q, a mutant unable to bind DNA, and of dnHSF1, a mutant lacking the activation domain, on the transcriptome of cells 6 and 24 h after heat shock. The primary response to heat shock (6 h recovery), of which 30 % was HSF1-dependent, had decayed 24 h after heat shock in control cells but was extended in HSF1 K80Q and dnHSF1 cells. Comparison with literature data showed that even the HSF1 dependent primary stress response is largely cell specific. HSF1 K80Q, but not HSF1 siRNA-treated, cells showed a delayed stress response: an increase in transcript levels of HSF1 target genes 24 h after heat stress. Knockdown of NRF2, but not of ATF4, c-Fos or FosB, inhibited this delayed stress response. EEF1D_L siRNA inhibited both the delayed and the extended primary stress responses, but had off target effects. In control cells an antioxidant response (ARE binding, HMOX1 mRNA levels) was detected 6 h after heat shock; in HSF1 K80Q cells this response was delayed to 24 h and the ARE complex had a different mobility. Inactivation of HSF1 thus affects the timing and nature of the antioxidant response and NRF2 can activate at least some HSF1 target genes in the absence of HSF1 activity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12192-012-0400-0) contains supplementary material, which is available to authorized users

Activation of the antioxidant response in methionine deprived human cells results in an HSF1-independent increase in HSPA1A mRNA levels

Contains fulltext : 111502.pdf (publisher's version ) (Closed access