Accelerating cardiac cine 3D imaging using k-t BLAST.

By exploiting spatiotemporal correlations in cardiac acquisitions using k-t BLAST, gated cine 3D acquisitions of the heart were accelerated by a net factor of 4.3, making single breathhold acquisitions possible. Sparse sampling of k-t space along a sheared grid pattern was implemented into a cine 3D SSFP sequence. The acquisition of low-resolution training data, which was required to resolve aliasing in the k-t BLAST method, was either interleaved into the sampling process or obtained in a separate prescan to allow for shorter breathhold durations in patients with heart disease. Volumetric datasets covering the heart with 20 slices at a spatial resolution of 2 x 2 x 5 mm3 were recorded with 20 cardiac phases in a total breathhold duration of 25-27 sec, or 18 sec if partial Fourier sampling was additionally employed. The feasibility of the method was demonstrated on healthy volunteers and on patients. The comparison of endocardial area derived from single slices of the 3D dataset with values extracted from separate single-slice acquisitions showed no significant differences. By shortening the acquisition substantially, k-t BLAST may greatly facilitate volumetric imaging of the heart for evaluation of regional wall motion and the assessment of ventricular volume and ejection fraction.     

k-t2 BLAST: exploiting spatiotemporal structure in simultaneously cardiac and respiratory time-resolved volumetric imaging.

Multidimensional imaging resolving both the cardiac and respiratory cycles simultaneously has the potential to describe important physiological interdependences between the heart and pulmonary processes. A fully five-dimensional acquisition with three spatial and two temporal dimensions is hampered, however, by the long acquisition time and low spatial resolution. A technique is proposed to reduce the scan time substantially by extending the k-t BLAST framework to two temporal dimensions. By sampling the k-t space sparsely in a lattice grid, the signal in the transform domain, x-f space, can be densely packed, exploiting the fact that large regions in the field of view have low temporal bandwidth. A volumetric online prospective triggering approach with full cardiac and respiratory cycle coverage was implemented. Retrospective temporal interpolation was used to refine the timing estimates for the center of k-space, which is sampled for all cardiac and respiratory time frames. This resulted in reduced reconstruction error compared with conventional k-t BLAST reconstruction. The k-t(2) BLAST technique was evaluated by decimating a fully sampled five-dimensional data set, and feasibility was further demonstrated by performing sparsely sampled acquisitions. Compared to the fully sampled data, a fourfold improvement in spatial resolution was accomplished in approximately half the scan time.     

Immunoglobulin mimicry by Hepatitis C Virus envelope protein E2

Hepatitis C virus (HCV) establishes persistent infection in the majority of infected individuals. The currently accepted hypothesis of immune evasion by antigenic variation in hypervariable region 1 (HVR1) of glycoprotein E2 does not however, explain the lack of subsequent immune recognition. Here, we show that the N-terminal region of E2 is antigenically and structurally similar to human immunoglobulin (Ig) variable domains. E2 is recognized by anti-human IgG antibodies and also possesses common amino acid (aa) sequence features of the conserved v-gene framework regions of human Ig light chains in particular but also heavy chains and T cell receptors. Using a position specific scoring system, the degree of similarity of HVR1 to Ig types correlated with immune escape and persistence in humans and experimentally infected chimpanzees. We propose a unique role for threshold levels of Ig molecular mimicry in HCV biology that not only advances our concept of viral immune escape and persistent infection but also provides insight into host-dependent disease patterns.     

Defensins: Natural component of human innate immunity

The widespread use of antibiotics has contributed to a huge increase in the number of resistant bacteria. New classes of drugs are therefore being developed of which defensins are a potential source. Defensins are a group of antimicrobial peptides found in different living organisms, involved in the first line of defense in their innate immune response against pathogens. This review summarizes the results of studies of this family of human antimicrobial peptides (AMPs). There is a special emphasis on describing the entire group and individual peptides, history of their discovery, their functions and expression sites. The results of the recent studies on the use of the biologically active peptides in human medicine are also presented. The pharmaceutical potential of human defensins cannot be ignored, especially considering their strong antimicrobial activity and properties such as low molecular weight, reduced immunogenicity, broad activity spectrum and resistance to proteolysis, but there are still many challenges and questions regarding the possibilities of their practical application.     

Isolation,synthesis and characterization of ω-TRTX-Cc1a,a novel tarantula venom peptide that selectively targets L-type CaV channels

Spider venoms are replete with peptidic ion channel modulators, often with novel subtype selectivity, making them a rich source of pharmacological tools and drug leads. In a search for subtype-selective blockers of voltage-gated calcium (Ca_V) channels, we isolated and characterized a novel 39-residue peptide, ω-TRTX-Cc1a (Cc1a), from the venom of the tarantula Citharischius crawshayi (now Pelinobius muticus). Cc1a is 67% identical to the spider toxin ω-TRTX-Hg1a, an inhibitor of Ca_V2.3 channels. We assembled Cc1a using a combination of Boc solid-phase peptide synthesis and native chemical ligation. Oxidative folding yielded two stable, slowly interconverting isomers. Cc1a preferentially inhibited Ba²⁺ currents (I_Ba) mediated by L-type (Ca_V1.2 and Ca_V1.3) Ca_V channels heterologously expressed in Xenopus oocytes, with half-maximal inhibitory concentration (IC₅₀) values of 825 nM and 2.24 μM, respectively. In rat dorsal root ganglion neurons, Cc1a inhibited I_Ba mediated by high voltage-activated Ca_V channels but did not affect low voltage-activated T-type Ca_V channels. Cc1a exhibited weak activity at Na_V1.5 and Na_V1.7 voltage-gated sodium (Na_V) channels stably expressed in mammalian HEK or CHO cells, respectively. Experiments with modified Cc1a peptides, truncated at the N-terminus (ΔG1–E5) or C-terminus (ΔW35–V39), demonstrated that the N- and C-termini are important for voltage-gated ion channel modulation. We conclude that Cc1a represents a novel pharmacological tool for probing the structure and function of L-type Ca_V channels.     

HSV-2的生物信息学分析及其探针设计的探讨

目的 利用生物信息学分析单纯疱疹病毒2型(HSV-2)基因序列的特点,设计HSV-2诊断芯片的Oligo探针. 方法 利用Matlab7.0和ANTHEPROTV5对HSV-2序列进行分析,并通过BLAST软件对HSV-2的DNA序列进行序列比对,得到有意义的特异序列;用生物学软件Oligo6.0设计特异性高、Tm值相近、长度均一的Oligo探针. 结果 利用Madab7.0和ANTHEPROT V5分析HSV-2二级结构的分布以及其理化性质,同时生物学软件Olig06.0获得13条60-merOligo探针.结论通过生物信息学设计HSV-2诊断芯片的探针,可为后期打印成DNA芯片,用于HSV-2的检测打下基础.     

应用系统发育分析方法鉴别近缘病原菌

目的:以gyrB基因序列为基础,采用系统发育分析方法构建进化树,对种系关系密切的病原菌进行区分鉴别。方法:测序获得本地区19株大肠埃希菌、13株志贺菌、2株豚鼠气单胞菌、2株嗜水气单胞菌、1株维隆气单胞菌的gyrB基因序列,并将其同公共数据库已有序列合并,构建进化树。分析各序列在树中的聚类关系,以此对菌株进行种水平分类鉴别,并同BLA ST查询结果相比较。结果:除鲍氏和痢疾志贺菌外,对检测的所有序列,在进化树上与之最邻近的5条序列均为该种菌株。而对一部分菌株,其BLA ST查询结果中含有其它菌种的或分类关系不明确的序列。结论:以系统发育方法对种系发生关系密切的病原菌序列进行鉴别,具有较好的分辨力和准确度。     

Presence of Propionibacterium acnes in blood components

BACKGROUND: Sterility testing, as part of the QC of blood components at the Japanese Red Cross Aichi Blood Center between April 1998 and March 2000, showed that 10 of 5568 tested blood components (0.18%), all of which were RBC concentrates, were contaminated with bacteria. Nine isolates were Propionibacterium acnes and one was Staphylococcus capitis. STUDY DESIGN AND METHODS: To investigate the molecular relatedness of eight available P. acnes isolates, 16S rRNA gene analysis and random amplified polymorphic DNA (RAPD) analysis were performed. RESULTS: DNA sequencing analysis of the 16S rRNA gene showed that five isolates were identified as distinct strains and that three had identical sequences. RAPD analysis in the latter three isolates showed that two exhibited indistinguishable banding patterns that differed from that of the third isolate. CONCLUSION: P. acnes was the most frequent contaminant of blood components, and six of eight isolates were molecularly unrelated. Further studies are necessary to investigate the precise mechanisms of contamination.     

Phylogenetic and developmental study of CD4, CD8 α and β T cell co-receptor homologs in two amphibian species, Xenopus tropicalis and Xenopus laevis

CD4 and CD8 co-receptors play critical roles in T cell development and activation by interacting both with T cell receptors and MHC molecules. Although homologs of these genes have been identified in many jawed vertebrates, there are still unresolved gaps concerning their evolution and specialization in MHC interaction and T cell function. Using experimental and computational procedures we identified CD4, CD8α and CD8β gene homologs both in Xenopus tropicalis, whose full genome has been sequenced, and its sister species Xenopus laevis. Multiple alignments of deduced amino acid sequences reveal a poor conservation of the residues involved in binding of CD4 to MHC class II, and CD8α to class I in non-mammalian species, presumably related to the co-evolutionary pressure of MHC I and II genes. Phylogenetic study suggests that Xenopodinae co-receptor genes are more closely related to their homologs in other tetrapods than those of bony fish. Furthermore, the developmental and cell-specific expression patterns of these genes in X. laevis are very similar to that of mammals. X. laevis CD4 is mainly expressed by peripheral non-CD8 T cells and detected in the thymus as early as four days post-fertilization (dpf) at the onset of thymic organogenesis. CD8β expression is specific to adult surface CD8⁺ T cells and thymocytes, and is first detected in the thymus at 5 dpf in parallel with productive TCRγ transrcipts, whereas productive TCRβ and α rearrangements are not detected before 7-9 dpf.     

k-t BLAST and k-t SENSE: dynamic MRI with high frame rate exploiting spatiotemporal correlations.

Dynamic images of natural objects exhibit significant correlations in k-space and time. Thus, it is feasible to acquire only a reduced amount of data and recover the missing portion afterwards. This leads to an improved temporal resolution, or an improved spatial resolution for a given amount of acquisition. Based on this approach, two methods were developed to significantly improve the performance of dynamic imaging, named k-t BLAST (Broad-use Linear Acquisition Speed-up Technique) and k-t SENSE (SENSitivity Encoding) for use with a single or multiple receiver coils, respectively. Signal correlations were learned from a small set of training data and the missing data were recovered using all available information in a consistent and integral manner. The general theory of k-t BLAST and k-t SENSE is applicable to arbitrary k-space trajectories, time-varying coil sensitivities, and under- and overdetermined reconstruction problems. Examples from ungated cardiac imaging demonstrate a 4-fold acceleration (voxel size 2.42 x 2.52 mm(2), 38.4 fps) with either one or six receiver coils. k-t BLAST and k-t SENSE are applicable to many areas, especially those exhibiting quasiperiodic motion, such as imaging of the heart, the lungs, the abdomen, and the brain under periodic stimulation.