抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

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Self-assembled monolayers of thiolates on metals as a form of nanotechnology.

I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

METHODS In this phase 3, open-label study, we randomly assigned previously untreated patients in East Asia who had advanced pulmonary adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib (250 mg per day) (609 patients) or carboplatin (at a dose calculated to produce an area under the curve of 5 or 6 mg per milliliter per minute) plus paclitaxel (200 mg per square meter of body-surface area) (608 patients). The primary end point was progression-free survival. RESULTS The 12-month rates of progression-free survival were 24.9% with gefitinib and 6.7% with carboplatin–paclitaxel. The study met its primary objective of showing the noninferiority of gefitinib and also showed its superiority, as compared with carboplatin– paclitaxel, with respect to progression-free survival in the intention-to-treat population (hazard ratio for progression or death, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). In the subgroup of 261 patients who were positive for the epidermal growth factor receptor gene (EGFR) mutation, progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin–paclitaxel (hazard ratio for progression or death, 0.48; 95% CI, 0.36 to 0.64; P<0.001), whereas in the subgroup of 176 patients who were negative for the mutation, progression-free survival was significantly longer among those who received carboplatin–paclitaxel (hazard ratio for progression or death with gefitinib, 2.85; 95% CI, 2.05 to 3.98; P<0.001). The most common adverse events were rash or acne (in 66.2% of patients) and diarrhea (46.6%) in the gefitinib group and neurotoxic effects (69.9%), neutropenia (67.1%), and alopecia (58.4%) in the carboplatin–paclitaxel group. CONCLUSIONS Gefitinib is superior to carboplatin–paclitaxel as an initial treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers in East Asia. The presence in the tumor of a mutation of the EGFR gene is a strong predictor of a better outcome with gefitinib. (ClinicalTrials.gov number, NCT00322452.)

https://www.nejm.org/doi/pdf/10.1056/NEJMoa0810699

Gefitinib or Carboplatin–Paclitaxel in Pulmonary Adenocarcinoma

Background Intratumor heterogeneity may foster tumor evolution and adaptation and hinder personalized-medicine strategies that depend on results from single tumor-biopsy samples. Methods To examine intratumor heterogeneity, we performed exome sequencing, chromosome aberration analysis, and ploidy profiling on multiple spatially separated samples obtained from primary renal carcinomas and associated metastatic sites. We characterized the consequences of intratumor heterogeneity using immunohistochemical analysis, mutation functional analysis, and profiling of messenger RNA expression. Results Phylogenetic reconstruction revealed branched evolutionary tumor growth, with 63 to 69% of all somatic mutations not detectable across every tumor region. Intratumor heterogeneity was observed for a mutation within an autoinhibitory domain of the mammalian target of rapamycin (mTOR) kinase, correlating with S6 and 4EBP phosphorylation in vivo and constitutive activation of mTOR kinase activity in vitro. Mutational intratumor heterogeneity was seen for multiple tumor-suppressor genes converging on loss of function; SETD2, PTEN, and KDM5C underwent multiple distinct and spatially separated inactivating mutations within a single tumor, suggesting convergent phenotypic evolution. Gene-expression signatures of good and poor prognosis were detected in different regions of the same tumor. Allelic composition and ploidy profiling analysis revealed extensive intratumor heterogeneity, with 26 of 30 tumor samples from four tumors harboring divergent allelic-imbalance profiles and with ploidy heterogeneity in two of four tumors. Conclusions Intratumor heterogeneity can lead to underestimation of the tumor genomics landscape portrayed from single tumor-biopsy samples and may present major challenges to personalized-medicine and biomarker development. Intratumor heterogeneity, associated with heterogeneous protein function, may foster tumor adaptation and therapeutic failure through Darwinian selection. (Funded by the Medical Research Council and others.)

http://www.therenegadecell.com/wiki/images/0/0d/NEJM-2012-366%2810%29-883.pdf

Intratumor heterogeneity and branched evolution revealed by multiregion sequencing.

Antiproteolytic action of orally delivered insulin using pH-responsive hydrogels in a rat burn model.

Metabolic depression is typically correlated with extended survival of environmental ehallenge and energy"limitation in early life stages of various invertebrates and vertebrates, Diapause is an ontogenetically-programmed reduction of development and often metabolism seen in many invertebrates. When embryos of Artemia handi'scana enter the state of diapause, the overall metabolic depression is estimated to be greater than 99%. These embryos also contain trehalose and express multiple isofbrms of Late Embryogenesis Abundant (LEA) proteins, constituents often

/pdf/diapause-and-anhydrobiosis-in-embryos-of-artemia-franciscana-5fma7m71ye.pdf

Diapause and anhydrobiosis in embryos of Artemia franciscana : metabolic depression, LEA proteins and water stress.

A microfluidic device that integrates mechanical squeezing and electrical stimulation delivers DNA to the nucleus of cells at a rate of millions of cells per minute.

Gene delivery: Suddenly squeezed and shocked

The antibody (Ab) array format provides a unique opportunity to pan and characterize multiple leukocyte subsets in parallel. However,thequestionsofreproducibilityandrobustnessofleukocytepanningon Abarraysneedtobeanswered for this technologyto become an immunophenotyping tool. The present study sought to address several of these questions, including: (1) purity of leukocytesubsetscapturedon Abregions,(2)dynamics ofleukocytebinding,(3) elimination ofnon-specificcelladhesion,and(4) standardization of cell washing conditions. Abs for CD4 T-cells, CD8 T-cells, CD36 monocytes, and CD16b neutrophils were dispensed onto standard glass slides containing a thin film of poly(ethylene glycol) (PEG) hydrogel. PEG gel coating was highly effective in eliminated non-specific cell adhesion on the surface. Incubation of the Ab arrays with red blood cell (RBC) depleted whole blood resulting in antigen-specific panning of leukocyte subsets on the respective Ab domains. A flow through chamber was employed to determine optimal shear stress conditions for removal of non-specifically attached cells. The purity of the four subsets remaining on the surface after washing was determined by Wright staining and immunofluorescence, and was found to be as follows: CD4 T-cells (99.2±0.3%), CD8 T-cells (98.7±0.3%), CD36 monocytes (97.2±0.9%), and CD16b neutrophils (99.1± 0.6%). In conclusion, the methods described in this study allow to separate whole blood into pure leukocyte subsets with minimal samplepreparation andhandling.Theseapproaches willbe valuableinthefuturedevelopmentofAbarraysastoolsforquantitative immunophenotyping of leukocytes.

Research paper Panning of multiple subsets of leukocytes on antibody-decorated poly(ethylene) glycol-coated glass slides

During the last 30 years, the semiconductor industry has had a significant influence on our society through advances in computers, communications, energy, and transportation. Semiconductor technology exploded following the development of exquisitely precise and versatile miniaturization techniques that allowed features on computer chips to be reduced to submicron dimensions, while substantially improving processing speed and drastically reducing cost. At the heart of this revolution was the creation of three-dimensional integrated circuit elements by a series of processes collectively known as “microfabrication”. During the past few years, the application of microfabrication techniques has entered the medical field and has initiated the development of powerful new diagnostic devices used for cancer, AIDS, and genetic diseases. In addition, microfabrication tools developed for the microelectronics industry have also entered the basic science arena and are beginning to serve as a driving force for discovery in cell biology, neurobiology, pharmacology, and tissue engineering.

Mehmet Toner

Papers

Antiproteolytic action of orally delivered insulin using pH-responsive hydrogels in a rat burn model.

Diapause and anhydrobiosis in embryos of Artemia franciscana : metabolic depression, LEA proteins and water stress.

Gene delivery: Suddenly squeezed and shocked

Research paper Panning of multiple subsets of leukocytes on antibody-decorated poly(ethylene) glycol-coated glass slides

Microfabrication in Biology and Medicine