Suppression of protein kinase C and the stimulation of glucocorticoid receptor synthesis by dexamethasone in human fibroblasts derived from tumor tissue

Exposure of fibroblasts derived from keloid tissues, desmoid and dermal tissue from individuals with Gardner's syndrome (GS) to dexamethasone resulted in the suppression of protein kinase C (PKC) activity and [3H]thymidine incorporation into DNA, and a 20-fold induction of glutamine synthetase activity. Treatment of GS and keloid fibroblasts with 0.1 microM dexamethasone for 36 h increased glucocorticoid receptor (GR) synthesis, as determined by [35S]methionine labeling and immunoprecipitation with a monoclonal antibody to the human GR. The suppression of PKC activity by dexamethasone was shown to result from a loss of protein mass as determined by immunoblotting using an antibody to PKC type III. In contrast to these results, exposure of fibroblasts isolated from normal tissues to dexamethasone did not result in the suppression PKC and [3H]thymidine incorporation, there was only a sixfold induction of glutamine synthetase, and a decrease of GR synthesis. As no primary receptor binding defect could be detected, the altered response of tumor cells to steroid-occupied receptor indicates a partial post-receptor binding defect in GS and keloid cells.     

The 1.2 Å crystal structure of an E. coli tRNA acceptor stem microhelix reveals two magnesium binding sites

tRNA identity elements assure the correct aminoacylation of tRNAs by the cognate aminoacyl-tRNA synthetases. tRNA^Ser belongs to the so-called class II system, in which the identity elements are rather simple and are mostly located in the acceptor stem region, in contrast to ‘class I’, where tRNA determinants are more complex and are located within different regions of the tRNA.The structure of an Escherichia coli tRNA^Ser acceptor stem microhelix was solved by high resolution X-ray structure analysis. The RNA crystallizes in the space group C2, with one molecule per asymmetric unit and with the cell constants a = 35.79, b = 39.13, c = 31.37 Å, and β = 111.1°. A defined hydration pattern of 97 water molecules surrounds the tRNA^Ser acceptor stem microhelix. Additionally, two magnesium binding sites were detected in the tRNA^Ser aminoacyl stem.     

Fifteen compelling open questions in plant cell biology

As scientists, we are at least as excited about the open questions—the things we do not know—as the discoveries. Here, we asked 15 experts to describe the most compelling open questions in plant cell biology. These are their questions: How are organelle identity, domains, and boundaries maintained under the continuous flux of vesicle trafficking and membrane remodeling? Is the plant cortical microtubule cytoskeleton a mechanosensory apparatus? How are the cellular pathways of cell wall synthesis, assembly, modification, and integrity sensing linked in plants? Why do plasmodesmata open and close? Is there retrograde signaling from vacuoles to the nucleus? How do root cells accommodate fungal endosymbionts? What is the role of cell edges in plant morphogenesis? How is the cell division site determined? What are the emergent effects of polyploidy on the biology of the cell, and how are any such “rules” conditioned by cell type? Can mechanical forces trigger new cell fates in plants? How does a single differentiated somatic cell reprogram and gain pluripotency? How does polarity develop de-novo in isolated plant cells? What is the spectrum of cellular functions for membraneless organelles and intrinsically disordered proteins? How do plants deal with internal noise? How does order emerge in cells and propagate to organs and organisms from complex dynamical processes? We hope you find the discussions of these questions thought provoking and inspiring.

We asked 15 experts to address what they consider to be the most compelling open questions in plant cell biology and these are their questions.     

Effect of chronotype on emotional processing and risk taking

There is increasing evidence to suggest that late chronotypes are at increased risk for depression. The putative psychological mechanisms underpinning this risk, however, have not been fully explored. The aim of the present study was to examine whether, similar to acutely depressed patients and other “at risk” groups, late chronotype individuals display biases in tasks assaying emotional face recognition, emotional categorisation, recognition and recall and attention. Late chronotype was associated with increased recognition of sad facial expressions, greater recall and reduced latency to correctly recognise previously presented negative personality trait words and reduced allocation of attentional resources to happy faces. The current results indicate that certain negative biases in emotional processing are present in late chronotypes and may, in part, mediate the vulnerability of these individuals to depression. Prospective studies are needed to establish whether the cognitive vulnerabilities reported here predict subsequent depression.     

Passive acoustic density estimation of sperm whales in the Tongue of the Ocean,Bahamas

Long‐term passive acoustic monitoring of marine mammals on navy ranges provides the opportunity to better understand the potential impact of sonar on populations. The navy range in Tongue of the Ocean (TOTO), Bahamas contains extensive hydrophone arrays, potentially allowing estimation of the density of deep diving, vocally active species such as the sperm whale (Physeter macrocephalus). Previous visual surveys in TOTO have been of limited spatio–temporal coverage and resulted in only sporadic sightings of sperm whales, whereas passive acoustic observations suggest the species is present year round. However, until now the means of acoustically determining the specific number of individuals in each cluster has been limited. We used recently developed algorithms to identify the number of echolocating whales present during a 42 d study period. We screened a 297 h acoustic data set to determine the proportion of time animals were present; fifty 10 min samples during presence were analyzed to estimate the number of individuals vocalizing during each sample. These counts were combined with an independent estimate of the proportion of 10 min periods when tagged animals vocalize. The estimated average density was 0.16 whales/1,000 km² (CV 27%; 95% CI 0.095–0.264). The method is potentially applicable to other areas containing dense hydrophone arrays.     

The Developmental Origins of Osteoporosis

Osteoporosis is one of the most prevalent skeletal disorders and has enormous public health consequences due to the morbidity and mortality of the resulting fractures. This article discusses the developmental origins of osteoporosis and outlines some of the modifiable and non-modifiable risk factors in both intrauterine and postnatal life that contribute to the later onset of osteoporosis. Evidence for the effects of birth size and early growth in both preterm and term born infants are discussed and the role of epigenetics within the programming hypothesis is highlighted. This review provides compelling evidence for the developmental origins of osteoporosis and highlights the importance of osteoporosis prevention at all stages of the life course.     

Adipose tissue compensates for defect of phosphatidylinositol 3'-kinase induced in liver and muscle by dietary fish oil in fed rats

The present work aimed to study in rats whether substitution of a low level of fish oil (FO; 2.2% of calories) into a low-fat diet (6.6% of calories from fat as peanut-rape oil or control diet) 1) has a tissue-specific effect on insulin signaling pathway and 2) prevents dexamethasone-induced alteration of insulin signaling in liver, muscle, and adipose tissue. Sixteen rats were used for study of insulin signaling, and sixteen rats received an oral glucose load (3 g/kg). Eight rats/group consumed control diet or diet containing FO over 5 wk. Four rats from each group received a daily intraperitoneal injection of saline or dexamethasone (1 mg.kg(-1).day(-1)) for the last 5 days of feeding. In liver, FO decreased phosphatidylinositol 3'-kinase (PI 3'-kinase) activity by 54% compared with control diet. A similar result was obtained in muscle. In both liver and muscle, FO clearly amplified the effect of dexamethasone. FO did not alter early steps of insulin signaling, and in muscle GLUT4 protein content remained unaltered. In adipose tissue, FO increased PI 3'-kinase activity by 74%, whereas dexamethasone decreased it by 65%; inhibition of PI 3'-kinase activity by dexamethasone was similar in rats fed FO or control diet, and GLUT4 protein content was increased by 61% by FO. Glycemic and insulinemic responses to oral glucose were not modified by FO. In conclusion, FO increased PI 3'-kinase activity in adipose tissue while inhibiting it in liver and muscle. The maintenance of whole body glucose homeostasis suggests an important role of adipose tissue for control of glucose homeostasis.