Active PI3K pathway causes an invasive phenotype which can be reversed or promoted by blocking the pathway at divergent nodes

The PTEN/PI3K pathway is commonly mutated in cancer and therefore represents an attractive target for therapeutic intervention. To investigate the primary phenotypes mediated by increased pathway signaling in a clean, patient-relevant context, an activating PIK3CA mutation (H1047R) was knocked-in to an endogenous allele of the MCF10A non-tumorigenic human breast epithelial cell line. Introduction of an endogenously mutated PIK3CA allele resulted in a marked epithelial-mesenchymal transition (EMT) and invasive phenotype, compared to isogenic wild-type cells. The invasive phenotype was linked to enhanced PIP(3) production via a S6K-IRS positive feedback mechanism. Moreover, potent and selective inhibitors of PI3K were highly effective in reversing this phenotype, which is optimally revealed in 3-dimensional cell culture. In contrast, inhibition of Akt or mTOR exacerbated the invasive phenotype. Our results suggest that invasion is a core phenotype mediated by increased PTEN/PI3K pathway activity and that therapeutic agents targeting different nodes of the PI3K pathway may have dramatic differences in their ability to reverse or promote cancer metastasis.     

Causes of death in the Kasekela chimpanzees of Gombe National Park, Tanzania

Understanding the rates and causes of mortality in wild chimpanzee populations has important implications for a variety of fields, including wildlife conservation and human evolution. Because chimpanzees are long-lived, accurate mortality data requires very long-term studies. Here, we analyze 47 years of data on the Kasekela community in Gombe National Park. Community size fluctuated between 38 and 60, containing 60 individuals in 2006. From records on 220 chimpanzees and 130 deaths, we found that the most important cause of mortality in the Kasekela community was illness (58% of deaths with known cause), followed by intraspecific aggression (20% of deaths with known cause). Previous studies at other sites also found that illness was the primary cause of mortality and that some epidemic disease could be traced to humans. As at other study sites, most deaths due to illness occurred during epidemics, and the most common category of disease was respiratory. Intraspecific lethal aggression occurred within the community, including the killing of infants by both males and females, and among adult males during the course of dominance-related aggression. Aggression between communities resulted in the deaths of at least five adult males and two adult females in the Kasekela and Kahama communities. The frequency of intercommunity violence appears to vary considerably among sites and over time. Intercommunity lethal aggression involving the Kasekela community was observed most frequently during two periods. Other less common causes of death included injury, loss of mother, maternal disability, and poaching.     

Rate of complications in scoliosis surgery – a systematic review of the Pub Med literature

Background

Spinal fusion surgery is currently recommended when curve magnitude exceeds 40–45 degrees. Early attempts at spinal fusion surgery which were aimed to leave the patients with a mild residual deformity, failed to meet such expectations. These aims have since been revised to the more modest goals of preventing progression, restoring 'acceptability' of the clinical deformity and reducing curvature. In view of the fact that there is no evidence that health related signs and symptoms of scoliosis can be altered by spinal fusion in the long-term, a clear medical indication for this treatment cannot be derived. Knowledge concerning the rate of complications of scoliosis surgery may enable us to establish a cost/benefit relation of this intervention and to improve the standard of the information and advice given to patients. It is also hoped that this study will help to answer questions in relation to the limiting choice between the risks of surgery and the "wait and see – observation only until surgery might be recommended", strategy widely used. The purpose of this review is to present the actual data available on the rate of complications in scoliosis surgery.

Materials and methods

Search strategy for identification of studies; Pub Med and the SOSORT scoliosis library, limited to English language and bibliographies of all reviewed articles. The search strategy included the terms; 'scoliosis'; 'rate of complications'; 'spine surgery'; 'scoliosis surgery'; 'spondylodesis'; 'spinal instrumentation' and 'spine fusion'.

Results

The electronic search carried out on the 1^st February 2008 with the key words "scoliosis", "surgery", "complications" revealed 2590 titles, which not necessarily attributed to our quest for the term "rate of complications". 287 titles were found when the term "rate of complications" was used as a key word. Rates of complication varied between 0 and 89% depending on the aetiology of the entity investigated. Long-term rates of complications have not yet been reported upon.

Conclusion

Scoliosis surgery has a varying but high rate of complications. A medical indication for this treatment cannot be established in view of the lack of evidence. The rate of complications may even be higher than reported. Long-term risks of scoliosis surgery have not yet been reported upon in research. Mandatory reporting for all spinal implants in a standardized way using a spreadsheet list of all recognised complications to reveal a 2-year, 5-year, 10-year and 20-year rate of complications should be established. Trials with untreated control groups in the field of scoliosis raise ethical issues, as the control group could be exposed to the risks of undergoing such surgery.     

Quantitative histology of the seasonal changes in the gonads of summer whiting, Sillago ciliata

The histology of the gonads of free and captive summer whiting, Sillago ciliata , were compared to assess the potential of this fish for aquaculture. There were no qualitative differences between the free and captive males: both completed spermatogenesis through to spermiation. The captive females were non-reproductive, reaching only the vitellogenic stage before the eggs were resorbed by atresia.
A reproductive score was devised to assess reproductive potential in the comparison of the two populations. The females in the captive population had lower reproductive potentials, as shown by the score, and started development a month later than the normal free population. The captive males had higher reproductive scores than the free fish but they were also not spawning and, therefore, the higher score indicated that this potential was not realized. The score provides a standard against which experimental results can be compared and subsequently assessed.     

Polarimetric detection in high-performance liquid chromatography

Chiroptical detection for HPLC is particularly useful as a selective detection method for chiral molecules, and in enantiomeric purity determination with partial chiral separation or without chiral separation. The recent development of laser-based polarimeters with microdegree sensitivity has increased the applicability of optical rotation detection in HPLC. The detection limit of these instruments is submicrogram on-column for many chiral compounds in analytical HPLC. A variety of applications of the selective detection of optically active molecules are reviewed. The use of polarimetric detection with partial chiral separation is considered, both as an aid to method development and for enantiomeric purity determination. Finally applications to enantiomeric purity determination without chiral separation are reviewed, with the dual use of nonchirally selective and chiroptical detectors to determine the total amount and optical purity of the analyte. Determinations of chiral purity for samples of high enantiomeric excess are described, which with laser-based instrumentation may give accuracies of better than +/- 1% with sample loadings of 50 micrograms on an achiral column. Applications to the study of enantioselective reactions are also considered, with determination of enantiomeric excess in near-racemates to better than +/- 0.1%.