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

Sequence similarity searching is a very important bioinformatics task. While Basic Local Alignment Search Tool (BLAST) outperforms exact methods through its use of heuristics, the speed of the current BLAST software is suboptimal for very long queries or database sequences. There are also some shortcomings in the user-interface of the current command-line applications. We describe features and improvements of rewritten BLAST software and introduce new command-line applications. Long query sequences are broken into chunks for processing, in some cases leading to dramatically shorter run times. For long database sequences, it is possible to retrieve only the relevant parts of the sequence, reducing CPU time and memory usage for searches of short queries against databases of contigs or chromosomes. The program can now retrieve masking information for database sequences from the BLAST databases. A new modular software library can now access subject sequence data from arbitrary data sources. We introduce several new features, including strategy files that allow a user to save and reuse their favorite set of options. The strategy files can be uploaded to and downloaded from the NCBI BLAST web site. The new BLAST command-line applications, compared to the current BLAST tools, demonstrate substantial speed improvements for long queries as well as chromosome length database sequences. We have also improved the user interface of the command-line applications.

/pdf/blast-architecture-and-applications-2udguz40ns.pdf

BLAST+: architecture and applications.

Spintronics, or spin electronics, involves the study of active control and manipulation of spin degrees of freedom in solid-state systems. This article reviews the current status of this subject, including both recent advances and well-established results. The primary focus is on the basic physical principles underlying the generation of carrier spin polarization, spin dynamics, and spin-polarized transport in semiconductors and metals. Spin transport differs from charge transport in that spin is a nonconserved quantity in solids due to spin-orbit and hyperfine coupling. The authors discuss in detail spin decoherence mechanisms in metals and semiconductors. Various theories of spin injection and spin-polarized transport are applied to hybrid structures relevant to spin-based devices and fundamental studies of materials properties. Experimental work is reviewed with the emphasis on projected applications, in which external electric and magnetic fields and illumination by light will be used to control spin and charge dynamics to create new functionalities not feasible or ineffective with conventional electronics.

/pdf/spintronics-fundamentals-and-applications-2dx38n6phu.pdf

Spintronics: Fundamentals and applications

Background and Purpose—The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audienc...

/pdf/guidelines-for-the-early-management-of-patients-with-acute-19udbft6e7.pdf

Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase e (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression.

https://cdr.lib.unc.edu/downloads/m900nw503

Comprehensive molecular characterization of human colon and rectal cancer

Detailed knowledge of magnetization reversal dynamics in lithographically patterned, micrometer-scale thin film ferromagnetic elements is of basic interest, and is relevant to the development of integrated device applications such as nonvolatile random access memory. We report a time-resolved Kerr microscopy study of the magnetic response of a 1×7 μm2 FeCo element inductively coupled to two crossed write wires. Beginning from a remanent state, switching rates are measured for single pulses of various amplitudes, and for two pulses with fixed amplitude and variable overlap. While using pulse amplitudes near the switching threshold, we observe the magnetization plateauing below the saturation level which we interpret as probabilistic switching caused by thermal fluctuations.

Time-resolved Kerr measurements of magnetization switching in a crossed-wire ferromagnetic memory element

Myocardial infarction is encountered rarely during pregnancy, but when it occurs the event is life-threatening to both mother and fetus. Data on maternal and fetal outcome are limited, but overall maternal mortality approaches 35%, and 40% of deaths occur during the third trimester. We present a case of myocardial infarction occurring at 38 weeks gestation, and discuss the anaesthetic management of the problems encountered during labour and delivery.

Anaesthetic Management of Myocardial Infarction in a Parturient

Acute focal bacterial nephritis (AFBN) is a rare, acute focal infection of the renal parenchyma without liquefaction. The pathogenesis is thought to be due to hematogenous infection or ascending infection from the lower urinary tract. Escherichia coli has been the major pathogen isolated in prior cases, but other Gram-negative enteric pathogens and Staphylococcus aureus have been reported as well. It is well described in children and adults with diabetes and organ transplantation, but has not been previously reported in healthy adults. We report a case of an immunocompetent adult female who presented with a methicillin-resistant Staphylococcus aureus bacteremia after a skin and soft tissue infection that resulted in AFBN.

Acute focal bacterial nephritis due to methicillin-resistant Staphylococcus aureus in an immunocompetent adult

A cardiac synaptosomal preparation developed by this laboratory was used to study neuronal calcium channels in aging rat heart. Ca2+ channels were quantified by measuring binding of iodinated omega conotoxin, which is reported to specifically block neuronal Ca2+ channels. We determined the binding of [125I]-omega conotoxin GVIA to a synaptosomal preparation from the hearts of 6- and 24-month-old male Fisher 344 rats. The maximum number of binding sites (Bmax +/- SD, fmol/mg protein) is lower in preparations from 24-month (2.2 +/- 0.6) than from 6-month (3.4 +/- 0.7)-old rats. This decrease in number of binding sites suggests an age-related reduction in the number of neuronal calcium channels. Since calcium is essential for exocytotic release of norepinephrine and is made available intracellularly through neuronal calcium channels, the reduction in neuronal calcium channel number may explain, in part, our previous observations of diminished release of norepinephrine in senescent hearts.

http://ebm.sagepub.com/content/199/4/453.full.pdf

Age-related decrease in omega conotoxin binding to rat cardiac synaptosomes.

We previously demonstrated an age-related decline in K+- induced norepinephrine (NE) release from cardiac synaptosomes prepared from 6- and 24- month- old male F344 rats. The purpose of the present study was to determine if the age- related decrease in NE release seen in male F344 rats is also present in female F344 rats. K+- induced NE release was assessed in cardiac synaptosomes prepared from 6-, 12-, 18-, and 24- month- old male and female F344 rats. NE release was significantly greater in young male rats, compared to old male rats. However, no age- related decrease in NE release was observed in the female rats. In contrast to previous observations in male rats, raising extracellular [Mg2+], an inorganic Ca2+ channel blocker, reduced NE release to the same extent in all female ages. Omega- conotoxin, an organic Ca2+ channel blocker, also decreased NE release to the same extent in all female ages. These studies suggest that in contrast to aging male rats, cardiac adrenergic nerve terminals of aging female rats maintain their capacity to release NE. (Aging Clin. Exp. Res. 7: 210–217, 1995)

Mark D. Johnson

Papers

Time-resolved Kerr measurements of magnetization switching in a crossed-wire ferromagnetic memory element

Anaesthetic Management of Myocardial Infarction in a Parturient

Acute focal bacterial nephritis due to methicillin-resistant Staphylococcus aureus in an immunocompetent adult

Age-related decrease in omega conotoxin binding to rat cardiac synaptosomes.

Effect of age on cardiac norepinephrine release in the female rat