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

Methods We identified 91 patients with World Health Organization grade II (atypical) meningioma managed at Dana-Farber/Brigham and Women’s Cancer Center between 1997 and 2011 A propensity score model incorporating age at diagnosis, gender, Karnofsky performance status, tumor location, tumor size, reason for diagnosis, and era of treatment was constructed using logistic regression for the outcome of receipt versus nonreceipt of radiation therapy Propensity scores were then used as continuous covariates in a Cox proportional hazards model to determine the adjusted impact of adjuvant radiation therapy on both local recurrence and the combined endpoint of use of salvage therapy and death due to progressive meningioma Results The median follow-up in patients without recurrent disease was 49 years After adjustment for pertinent confounding variables, radiation therapy was associated with decreased local recurrence in those undergoing gross total resection (hazard ratio, 025; 95% CI, 007–096; P ¼ 04) No differences in overall survival were seen in patients who did and did not receive radiation therapy Conclusion Patients who have had a gross total resection of an atypical meningioma should be considered for adjuvant radiation therapy given the improvement in local control Multicenter, prospective trials are required to definitively evaluate the potential impact of radiation therapy on survival in patients with atypical meningioma

/pdf/adjuvant-radiation-therapy-local-recurrence-and-the-need-for-fwqcvuja5t.pdf

Adjuvant radiation therapy, local recurrence, and the need for salvage therapy in atypical meningioma

Epidural fentanyl for postcesarean delivery pain management.

Injection of opioids into the epidural space produces postoperative analgesia by acting on receptors in lamina 11, IV, and V of the substantia gelatinosa (1). Morphine, due to its low lipid solubility produces numerous side effects when injected into the epidural space; most notably delayed respiratory depression (2). Fentanyl, a highly lipid soluble narcotic agonist, has a more rapid onset of action and a significantly lower incidence of side effects than those of morphine. In a dose-response study in patients after cesarean delivery, 50 pg of epidural fentanyl was found to provide maximal analgesia with minimal incidence of side effects (3). The effect of varying the volume of injectate on the onset, duration, and incidence of side effects produced by 50 pg of fentanyl has not been reported. This standard dose of fentanyl diluted in larger volumes could increase the surface area of drug exposure and thus augment the number of opioid receptors affected. Conversely, diluting the opioid in greater volume may reduce the concentration gradient between the central nervous system and epidural space and thereby decrease both the rapidity of onset and duration of analgesia. Fentanyl is being given epidurally in several different dilutions. To determine the most effective diluent volume, a double-blind, randomized study was undertaken with varying volumes of normal saIine solution to dilute a single 50 pg dose of epidural fentanyl.

Effect of diluent volume on analgesia produced by epidural fentanyl.

We have studied the effect of salmeterol on both P. aeruginosa interactions with the mucosa of nasal turbinate organ cultures and on pyocyanin-induced (20 microg/ml) and elastase-induced (100 microg/ml) damage to nasal epithelial cells. Organ cultures were exposed to salmeterol either by preincubation with 4 x 10(-7) M salmeterol for 30 min or by pipetting 20 microl of 4 x 10(-7) M salmeterol onto the organ culture surface immediately prior to bacterial inoculation. Infected organ cultures (8 h) had significantly (p < or = 0.01) increased epithelial damage, and P. aeruginosa was predominantly associated with damaged epithelium and mucus. Salmeterol significantly (p < or = 0.02) reduced epithelial damage caused by infection and the total number of adherent bacteria (p < or = 0.05), but bacterial distribution on the mucosa was unchanged. Nasal epithelial cells incubated with pyocyanin (20 microg/ml) or elastase (100 microg/ml) for 3 h had significantly (p < or = 0.05) increased cytoplasmic blebbing and mitochondrial damage versus control values. Elastase also significantly (p < or = 0.05) increased cell projection and reduced the level of ciliation. Cells preincubated with salmeterol (2 x 10(-7) M) showed a significant reduction in some features of cell damage caused by both toxins, which was inhibited by the beta2-adrenoceptor antagonist propranolol. Our results indicate that salmeterol reduces P. aeruginosa-induced damage to both organ culture and nasal epithelium.

Effect of salmeterol on Pseudomonas aeruginosa infection of respiratory mucosa.

The complexity of glioblastoma multiforme (GBM) and its distinct pathophysiology belong to a unique brain microenvironment and its cellular interactions. Despite extensive evidence of a role for microRNAs in GBM cells, little is known about microRNA-dependent communication between different cellular compartments of the microenvironment that may contribute to the tumor phenotype. While the majority of microRNAs are found intracellularly, a significant number of microRNAs have been observed outside of cells, often encapsulated in secreted extracellular vesicles (EVs). The function of these circulating/secreted microRNAs has not been explored in the context of the brain tumor microenvironment. Establishing how microRNAs are involved in the regulation of oncogenic signaling networks between tumor cells and stroma is likely to add a needed additional layer of complexity to the tumor network, consisting of intercellular communication. More importantly, microRNA/EV signaling may provide an additional therapeutic target for this deadly disease.

/pdf/belonging-to-a-network-micrornas-extracellular-vesicles-and-23oxckxpdq.pdf

Mark D. Johnson

Papers

Adjuvant radiation therapy, local recurrence, and the need for salvage therapy in atypical meningioma

Epidural fentanyl for postcesarean delivery pain management.

Effect of diluent volume on analgesia produced by epidural fentanyl.

Effect of salmeterol on Pseudomonas aeruginosa infection of respiratory mucosa.

Belonging to a network—microRNAs, extracellular vesicles, and the glioblastoma microenvironment