Meta-analysis of heat- and chemically upregulated chaperone genes in plant and human cells

Molecular chaperones are central to cellular protein homeostasis. In mammals, protein misfolding diseases and aging cause inflammation and progressive tissue loss, in correlation with the accumulation of toxic protein aggregates and the defective expression of chaperone genes. Bacteria and non-diseased, non-aged eukaryotic cells effectively respond to heat shock by inducing the accumulation of heat-shock proteins (HSPs), many of which molecular chaperones involved in protein homeostasis, in reducing stress damages and promoting cellular recovery and thermotolerance. We performed a meta-analysis of published microarray data and compared expression profiles of HSP genes from mammalian and plant cells in response to heat or isothermal treatments with drugs. The differences and overlaps between HSP and chaperone genes were analyzed, and expression patterns were clustered and organized in a network. HSPs and chaperones only partly overlapped. Heat-shock induced a subset of chaperones primarily targeted to the cytoplasm and organelles but not to the endoplasmic reticulum, which organized into a network with a central core of Hsp90s, Hsp70s, and sHSPs. Heat was best mimicked by isothermal treatments with Hsp90 inhibitors, whereas less toxic drugs, some of which non-steroidal anti-inflammatory drugs, weakly expressed different subsets of Hsp chaperones. This type of analysis may uncover new HSP-inducing drugs to improve protein homeostasis in misfolding and aging diseases

Compartmentalized cancer drug discovery targeting mitochondrial Hsp90 chaperones

There is a plethora of attractive drug targets in cancer, but their therapeutic exploitation proved more difficult than expected, and only rarely truly successful. One possibility not often considered in drug discovery is that cancer signaling pathways are not randomly arranged in cells, but orchestrated in specialized subcellular compartments. The identification of heat shock protein-90 (Hsp90) chaperones in mitochondria of tumors, but not most normal tissues, provides an example of a compartmentalized network of cell survival, opening fresh prospects for novel, subcellularly targeted cancer drug discovery.close252

Cultural Considerations in the Context of Romantic Relationships

It is estimated that about one-third of couples experience distress or discord at some point in the course of their relationship. The early literature of marriage and committed relationships focused nearly exclusively on White, heterosexual, non-Hispanic couples, but over the past couple of decades, there has been increased focus on the dynamics and specific needs of couples from different ethnic backgrounds as well as same-sex couples. In this chapter, we summarize some of the major challenges and threats to relationship well-being for African American, Hispanic American, Asian American, Native American, and same-sex couples. Some of the challenges discussed in this chapter include racism and discrimination, financial strain and work stress, acculturation, and negative historical or societal influences. We also have tried to highlight important areas of strength for couples that therapists can help clients enhance, including religiosity and spirituality and support from family or friends