GREM1 is associated with metastasis and predicts poor prognosis in ER-negative breast cancer patients

The exposure of phosphatidylserine (PS) on the outer plasma membrane has long been considered a unique feature of apoptotic cells. Together with other “eat me” signals, it enables the recognition and phagocytosis of dying cells (efferocytosis), helping to explain the immunologically-silent nature of apoptosis. Recently, however, PS exposure has also been reported in non-apoptotic forms of regulated inflammatory cell death, such as necroptosis, challenging previous dogma. In this review, we outline the evidence for PS exposure in non-apoptotic cells and extracellular vesicles (EVs), and discuss possible mechanisms based on our knowledge of apoptotic-PS exposure. In addition, we examine the outcomes of non-apoptotic PS exposure, including the reversibility of cell death, efferocytosis, and consequent inflammation. By examining PS biology, we challenge the established approach of distinguishing apoptosis from other cell death pathways by AnnexinV staining of PS externalization. Finally, we re-evaluate how PS exposure is thought to define apoptosis as an immunologically silent process distinct from other non-apoptotic and inflammatory cell death pathways. Ultimately, we suggest that a complete understanding of how regulated cell death processes affect the immune system is far from being fully elucidated.     

Bacteriological quality of organically grown leaf lettuce in Norway

AIM: To investigate bacteriological quality in organically grown leaf lettuce, including the presence of selected pathogenic bacteria, and to obtain information about organic lettuce production, including fertilizing regimes. METHODS AND RESULTS: Altogether 179 samples of Norwegian organically grown lettuce were collected from 12 producers. Escherichia coli was isolated from 16 of the lettuce samples, but in 12 of these contamination was sufficiently low (<100 CFU g(-1)) that they would be considered to be of acceptable bacteriological quality. Escherichia coli O157 and Salmonella were not detected in any of the samples. Listeria monocytogenes serogroups 1 and 4 were isolated from two samples. CONCLUSIONS: Organic lettuce produced in Norway was generally of acceptable bacteriological quality, but the results show that contamination of organic lettuce with E. coli and L. monocytogenes do occasionally occur. SIGNIFICANCE AND IMPACT OF THE STUDY: These results suggest that organically grown lettuce may be contaminated with E. coli and L. monocytogenes during cultivation.     

Changes in distribution of actin mRNA in different polysome fractions following stimulation of MPC-11 cells

Individual mRNA species have been shown to differ both with respect to localization in the cell, and in their distribution upon stimulation of cells with different signals. In this study we have examined the distribution of actin mRNA in the free, cytoskeletal-bound, and membrane-bound RNA fractions, both in starved cells, and in response to stimulation by feeding. These results were then compared with mRNAs for glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and histone H4. The results we obtained showed that actin mRNA was located in the free RNA fraction in starved cells, while upon stimulation it was located both in the free, and in the cytoskeletal fraction; no redistribution of GAPDH mRNA occurred between the three RNA fractions, while H4 mRNA showed a different localization upon stimulation. Incubation with the drugs actinomycin-D and cycloheximide showed that an altered localization of actin mRNA from free in starved cells to free and cytoskeletal mRNA fractions following stimulation, was dependent on RNA synthesis, and not on protein synthesis.     

Manipulation of male quality in wild tits: effects on paternity loss

Extrapair paternity (EPP) has proved to be widespread and highlyvariable among birds and other taxa, including socially monogamousspecies. A multitude of hypotheses have been put forward toexplain this variation, but its occurrence is not fully understood.Male age, social dominance rank, song and breeding density orsynchrony have been among the suggested correlates of EPP, butresults so far are inconclusive. We interspecifically cross-fosteredblue tits (Parus caeruleus) and great tits (Parus major) inthe wild, thus manipulating males to exhibit reduced socialdominance rank, sing aberrant songs, and consequently be perceivedas low-quality males as compared to controls. This allowed usto test if male quality had an influence on loss of paternity.We found no statistically significant differences between cross-fosteredand control males of either species, neither with respect tolevels of cuckoldry nor proportions of extrapair young (EPY)in the broods. Paternity levels were comparable to other studieson the same species. No effect of density could be detectedon levels of EPP either, while an age effect seemed to be presentat least in the blue tit, EPY being almost absent in broodsof older blue tit males. We conclude that the effects of malequality on paternity loss are minor, if any, in these populations.     

TORC1 is essential for NF1-associated malignancies

Inactivating mutations in NF1 underlie the prevalent familial cancer syndrome neurofibromatosis type 1 [1]. The NF1-encoded protein is a Ras GTPase-activating protein (RasGAP) [2]. Accordingly, Ras is aberrantly activated in NF1-deficient tumors; however, it is unknown which effector pathways critically function in tumor development. Here we provide in vivo evidence that TORC1/mTOR activity is essential for tumorigenesis. Specifically, we show that the mTOR inhibitor rapamycin potently suppresses the growth of aggressive NF1-associated malignancies in a genetically engineered murine model. However, in these tumors rapamycin does not function via mechanisms generally assumed to mediate tumor suppression, including inhibition of HIF-1alpha and indirect suppression of AKT, but does suppress the mTOR target Cyclin D1 [3]. These results demonstrate that mTOR inhibitors may be an effective targeted therapy for this commonly untreatable malignancy. Moreover, they indicate that mTOR inhibitors do not suppress all tumor types via the same mechanism, suggesting that current biomarkers that rely on HIF-1alpha suppression may not be informative for all cancers. Finally, our results reveal important differences between the effects of mTOR inhibition on the microvasculature in genetically engineered versus xenograft models and indicate that the former may be required for effective preclinical screening with this class of inhibitors.     

Dysregulation of Ack1 inhibits down-regulation of the EGF receptor

The protein tyrosine kinase Ack1 has been linked to cancer when over-expressed. Ack1 has also been suggested to function in clathrin-mediated endocytosis and in down-regulation of the epidermal growth factor (EGF) receptor (EGFR). We have studied the intracellular localization of over-expressed Ack1 and found that Ack1 co-localizes with the EGFR upon EGF-induced endocytosis in cells with moderate over-expression of Ack. This co-localization is mainly observed in early endosomes. Furthermore, we found that over-expression of Ack1 retained the EGFR at the limiting membrane of early endosomes, inhibiting sorting to inner vesicles of multivesicular bodies. Down-regulation of Ack1 in HeLa cells resulted in reduced rate of (125)I-EGF internalization, whereas internalization of (125)I-transferrin was not affected. In cells where Ack1 had been knocked down by siRNA, recycling of internalized (125)I-EGF was increased, while degradation of (125)I-EGF was inhibited. Together, these data suggest that Ack1 is involved in an early step of EGFR desensitization.     

The influence of different parental combinations and incubation temperature on the RNA and DNA content of herring larvae at hatching: a pilot study

In four half-sib pairings, herring mothers affected the standard length, dry weight, and RNA and DNA content of their progeny, while fathers affected larval RNA and DNA content. The amounts of RNA and DNA in offspring from one male were also influenced by temperature in that the highest RNA contents were found at the lowest temperature and highest DNA contents at the highest temperature. The results indicate that both environmental and genetic factors influence nucleic acid contents of young herring larvae, and this may limit the suitability of RNA : DNA ratio as a condition measure of newly hatched herring larvae.