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

/pdf/self-assembled-monolayers-of-thiolates-on-metals-as-a-form-1neb0hj3k4.pdf

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.

Cryopreservation of starfish oocytes

Thought leaders Stefanie Jeffrey and Mehmet Toner introduce the Lab on a Chip Personalised Medicine: Liquid Biopsy thematic collection.

Liquid biopsy: a perspective for probing blood for cancer.

Human infertility can be treated using assisted reproductive technology (ART) such as intracytoplasmic sperm injection (ICSI). But current ART techniques suffer from multiple cumbersome processes requiring technically skilled personnel. Microfluidics technologies offer unique opportunities to streamline ART procedures, reduce stress imposed upon gametes and embryos, and minimize the operator-to-operator variability. However, there have been no automated and continuous processing systems that can reduce the dependence on well-trained embryologists to obtain ICSI-ready oocytes from patients. In this study, using mouse models, we developed a microfluidic device to denude oocytes from the surrounding cumulus-corona cell mass, facilitating the evaluation of oocyte quality and the injection of sperm. Enzyme-treated cumulus-oocyte complexes pass through a series of jagged-surface constriction microchannels of optimized geometries. The jagged inner wall of constriction channels facilitates stripping off of the cumulus-corona cell mass. Oocytes that were denuded by the device showed comparable fertilization and developmental competence compared with mechanical pipetting. The device developed in this study achieves the automation of a manual process for oocyte denudation in a continuous flow, as well as improving standardization and ease-of-use. Our denudation-on-a-chip approach requires inexpensive and simple equipment, which represents one step forward towards improving the accessibility and affordability of assisted reproductive therapy.

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On-chip oocyte denudation from cumulus-oocyte complexes for assisted reproductive therapy.

Engineering Desiccation Tolerance in Mammalian Cells: Tools and Techniques

Methods and systems for selectively capturing analytes, such as cells, e.g., circulating tumor cells (CTCs), from fluid samples are disclosed. The methods include contacting the sample with an analyte binding moiety that selectively binds to the analytes; optionally separating first components of the sample including a majority of the analytes bound to the binding moieties from second components of the sample using size-based separation, e.g., in a microfluidic channel; adding to the first components of the sample a plurality of binding agents under conditions that enable a plurality of the binding agents to be linked to the analyte binding moieties to form multivalent tagging agents bound to the analyte; passing the first components of the sample past a surface to which is attached a plurality of capture agents that selectively bind to the binding agents; and capturing the analytes by providing conditions that enable the multivalent tagging agents bound to the analytes to bind to one or more of the capture agents.

Mehmet Toner

Papers

Cryopreservation of starfish oocytes

Liquid biopsy: a perspective for probing blood for cancer.

On-chip oocyte denudation from cumulus-oocyte complexes for assisted reproductive therapy.

Engineering Desiccation Tolerance in Mammalian Cells: Tools and Techniques

Microfluidic devices for the capture of biological sample components