BACKGROUND & AIMS: BACKGROUND:We examined loss of heterozygosity (LOH) of the P53 gene in bladder cancer, and investigated the role of the P53 gene on malignant progression of papillary tumors. In addition, the clonality of recurrent bladder cancer was examined. METHODS:LOH of the P53 gene was analyzed in 67 bladder cancers from 47 patients. DNA was extracted from formalin-fixed, paraffin-embedded tissues, amplified by the polymerase chain reaction (PCR) at 3 polymorphic loci in the P53 gene, and analyzed with nonradioisotopic single-strand conformation polymorphism (Non-RI SSCP) analysis. RESULTS:Out of 40 informative samples, LOH was detected in 13 samples, containing 4 of 7 in grade 3 (57%), 9 of 23 in grade 2 (39%), and none of 10 in grade 1 (10%). Statistical significance was observed between the LOH in grades 1 and 2, and in grades 1 and 3. An analysis of 5 cases showing malignant progression revealed that 3 (60%) showed an LOH in the primary tumor, and 2 showed LOH in recurrent tumors, in contrast to LOH found in 3 cases of 19 (16%) not showing malignant progression. Four cases with metachronous recurrence exhibited LOH; 2 at recurrent tumors, 1 only at the initial tumor, and 1 at both tumors. CONCLUSIONS:The alterations of the P53 gene were considered to correlate with tumor grade, and contribute to the malignant progression of bladder cancer. LOH in the P53 gene may serve as a clinical indicator for prognosis in superficial bladder cancer.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Current genomic research methods provide researchers with enormous amounts of data. Combining data from different high-throughput research technologies commonly available in biological databases can lead to novel findings and increase research efficiency. However, combining data from different heterogeneous sources is often a very arduous task. These sources can be different microarray technology platforms, genomic databases, or experiments performed on various species. Our aim was to develop a software program that could facilitate the combining of data from heterogeneous sources, and thus allow researchers to perform genomic cross-platform/cross-species studies and to use existing experimental data for compendium studies. RESULTS:We have developed a web-based software resource, called CROPPER that uses the latest genomic information concerning different data identifiers and orthologous genes from the Ensembl database. CROPPER can be used to combine genomic data from different heterogeneous sources, allowing researchers to perform cross-platform/cross-species compendium studies without the need for complex computational tools or the requirement of setting up one's own in-house database. We also present an example of a simple cross-platform/cross-species compendium study based on publicly available Parkinson's disease data derived from different sources. CONCLUSION:CROPPER is a user-friendly and freely available web-based software resource that can be successfully used for cross-species/cross-platform compendium studies.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:The objective of our study was to evaluate the outcome of lobular neoplasia diagnosed at 11-gauge stereotactic vacuum-assisted biopsy (SVAB). MATERIALS AND METHODS:Retrospective review of 1,819 lesions sampled with 11-gauge SVAB yielded 27 patients with lobular neoplasia as the most severe pathologic entity diagnosed. Patients with lobular neoplasia associated with atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), or infiltrating carcinoma were excluded. Twenty patients underwent surgical excisional biopsy, and seven patients were followed mammographically for a mean of 52 months (range, 14-67 months). Mammographic lesion type, number of specimens obtained per lesion, and specific histologic features related to lobular carcinoma in situ (LCIS) were assessed. Results were compared with histologic findings at surgery or mammographic follow-up. RESULTS:Nineteen lesions presented mammographically as microcalcifications, four as masses, three as masses with associated microcalcifications, and one as architectural distortion. A mean of 13 specimens were obtained per lesion. Carcinoma was found at surgical excision in 19% of the lesions (5/27). Lesions were upgraded to DCIS (n = 2), invasive lobular carcinoma (n = 2), and mixed invasive ductal and lobular carcinoma (n = 1). In addition to the diagnosis of lobular neoplasia at SVAB, one patient presented with synchronous infiltrating ductal carcinoma in the contralateral breast, and two patients developed metachronous infiltrating ductal carcinoma in a different quadrant of the ipsilateral breast. Twelve of the 27 lesions included LCIS. These lesions were evaluated pathologically to distinguish the classic (10/12) from the pleomorphic (2/12) form of this entity. Ten of the 12 LCIS cases underwent surgical excisional biopsy with four of the five upgrades occurring in these patients. Only one of these patients was shown to have the pleomorphic type of LCIS. Lesions in seven patients who underwent mammographic follow-up remained stable. CONCLUSION:The known association of lobular neoplasia with high-risk and malignant lesions at surgical biopsy requires careful consideration when lobular neoplasia is diagnosed as the most severe histologic entity at SVAB. The diagnosis of lobular neoplasia at 11-gauge SVAB is not reliable in view of the 19% upgrade rate at the time of surgical excisional biopsy in our study. No predictive mammographic features allowed distinction between the patients with lesions that were upgraded at the time of surgery from those whose lesions were not upgraded.

背景与目标：

BACKGROUND & AIMS: Previous mutagenesis studies with bacteriorhodopsin have shown that reprotonation of the Schiff's base is the rate-limiting step in the photocycle of the D96N mutant, whereas retinal re-isomerization and return of the protein to the initial state constitute the rate-limiting events in the photocycle of the L93A mutant. Thus, in the D96N mutant, decay of the M intermediate is slowed down by more than 100-fold at pH 7. In the L93A mutant, decay of the O intermediate is slowed down by 250-fold. We report here that in the L93A, D96N double mutant, decay of the M intermediate, as well as the formation and decay of the O intermediate, are slowed down dramatically. The photocycle is completed by the decay of a long-lived O intermediate, as in the L93A mutant. The decay of the M and O intermediates in the double mutant parallels the behavior seen in the single mutants over a wide temperature and pH range, arguing that the observed independence is an intrinsic property of the mutant. The slow decay of the M and O intermediates can be selectively and independently reversed under conditions identical to those used for the corresponding intermediates in the D96N and L93A single mutants. Because the effects of the two individual mutations are preserved in the double mutant and can be independently reversed, we conclude that residues Asp 96 and Leu 93 act independently and at different stages of the bacteriorhodopsin photocycle. These results also show that formation of the O intermediate only requires protonation of the Schiff's base and is independent of the protonation of Asp 96 from the aqueous medium.

背景与目标： 先前对细菌视紫红质的诱变研究表明，席夫碱的再质子化是D96N突变体光循环中的限速步骤，而视网膜再异构化和蛋白质返回到初始状态则构成了光循环中的限速事件。L93A突变体。因此，在D96N突变体中，M中间体的衰变在ph7下减慢了100倍以上。在L93A突变体中，O中间体的衰变减慢250倍。我们在这里报告说，在L93A，D96N双突变体中，M中间体的衰变以及O中间体的形成和衰变显着减慢。像L93A突变体一样，通过长寿命O中间体的衰变来完成光循环。双突变体中M和O中间体的衰变与在宽温度和pH范围内单个突变体中看到的行为相似，认为观察到的独立性是突变体的内在特性。M和O中间体的缓慢衰变可以在与D96N和L93A单个突变体中相应中间体所使用的条件相同的条件下选择性地和独立地逆转。由于两个个体突变的作用保留在双突变体中并且可以独立逆转，因此我们得出结论，残基Asp 96和Leu 93独立且在细菌视紫红质光循环的不同阶段起作用。这些结果还表明，O中间体的形成仅需要席夫碱的质子化，并且与水性介质中Asp 96的质子化无关。

BACKGROUND & AIMS: PURPOSE:To determine the clinical importance and relative value of reinterpreting brain CT imaging studies by subspecialty experts regarding changes in clinical management. METHODS:Computerized records were queried at two institutions during the years 2002-2003 for both primary interpretation by board-certified nonneuroradiologists and secondary interpretation by three neuroradiologists. A total of 1,081 cases were reviewed. Each case was initially interpreted as an emergent or urgent study. The reinterpreted studies were scored as concordant or discordant by the subspecialty experts. The discordant studies were then categorized as a "major discordance" if there was a change in clinical management, or as a "minor discordance" if there was no impact or change in clinical management. RESULTS:Of the 1,081 studies reviewed, 14 studies were identified as discordant (1.3%). Of those discordant studies, four were categorized as major discrepancies necessitating a change in clinical management (0.4 %). Ten were categorized as minor discrepancies (0.9%). There were no permanent adverse outcomes with respect to morbidity and mortality as a result of any discrepancy. CONCLUSION:The vast majority of interpreted head CT cases read by board-certified general radiologists do not result in discordant interpretations as verified by subspecialty experts. Discordant interpretations did not result in changes in clinical management in most cases. Double reading of head CTs by subspecialty experts appears to be an inefficient method of substantially improving imaging health quality outcomes.

背景与目标：

BACKGROUND & AIMS: :Extensive laboratory testing is often performed in the emergency department evaluation of the new-onset seizure patient. To determine the utility of such testing, a prospective study of patients with a new-onset seizure presenting to the ED of an inner-city, university-affiliated teaching hospital was done. One hundred thirty-six patients were entered into the study between October 1984 and January 1988. All patients had uniform data collection performed. Pertinent historical information and physical examination findings were recorded on a standardized form before laboratory abnormality was a sole or contributory cause of the seizure disorder. These included four patients with hypoglycemia, four with hyperglycemia, two with hypocalcemia, and one with hypomagnesemia. Only two cases (hypoglycemia) were not suspected on the basis of findings on the history or physical examination. In ED patients, the incidence of a new-onset seizure due to a correctable metabolic disturbance is low. We conclude that, with the exception of the serum glucose, the extensive ED laboratory workup often done for the evaluation of a new-onset seizure is unnecessary. Further test ordering should be directed by the medical history and physical examination.

背景与目标： : 在急诊科对新发癫痫患者的评估中，经常进行广泛的实验室测试。为了确定这种测试的实用性，对向市中心大学附属教学医院的ED呈递的新发癫痫发作患者进行了前瞻性研究。在1984年10月和1988年1月之间，有136名患者进入了研究。所有患者均进行了统一的数据收集。在实验室异常是癫痫发作的唯一或促成原因之前，将相关的历史信息和体格检查结果记录在标准化表格上。其中包括4名低血糖患者，4名高血糖患者，2名低钙血症患者和1名低镁血症患者。根据病史或体格检查发现，仅怀疑有2例 (低血糖)。在ED患者中，由于可纠正的代谢紊乱而引起的新发癫痫发作的发生率较低。我们得出的结论是，除血清葡萄糖外，通常不需要进行广泛的ED实验室检查以评估新发癫痫发作。进一步的检查顺序应由病史和体格检查指示。

BACKGROUND & AIMS: AIM:To report the patterns and sites of 18-FDG uptake in patients of presumed ocular tuberculosis. MATERIALS AND METHODS:The clinical and investigational findings of 11 patients were reviewed retrospectively. These included 6 males and 5 females with a mean age of 46.2 years. 21 eyes were included in the data analysis. Clinical presentations include 15 eyes with anterior uveitis, 2 eyes with retinal vasculitis, 2 eyes with panuveitis and 2 eyes with multifocal choroidopathy. RESULTS:Two distinct patterns of systemic uptake emerged. Pattern 1: No detectable systemic uptake (4 patients). Pattern 2: Detectable systemic uptake. a. Chest disease only (2 patients). b. Disseminated pattern, uptake seen at multiple sites (4 patients). c. Extrapulmonary only (1 patient). CONCLUSIONS:Ocular tuberculosis may often be part of a wider disseminated disease.

背景与目标：

BACKGROUND & AIMS: :T cell regulation of the generation of thyroglobulin plaque-forming cells (Tg PFC) and protein A plaque-forming cells (Prot A PFC) was investigated using lymphocytes from patients with autoimmune thyroid disease. T and B cell mixed cultures (T-B MC) were carried out without mitogenic or antigenic stimulation to identify physiological T cell effects in the system. Tg PFC were found in 8 (44%) of 18 patients who had high titers of thyroglobulin antibody in their sera. Tg-specific and nonspecific immunoregulation by T cells from patients and normal subjects was studied using B cells from these eight patients in the T-B MC system. Remarkably lower values of Tg PFC induction compared to Prot A PFC induction were found after T cell addition. Normal T cells inhibited Tg PFC induction, but patient T cells did not, while the same extent of helper effects were found on Prot A PFC induction by the addition of patient and normal T cells. Irradiation (1500 rads) of T cells from patients and normal subjects significantly enhanced both TgPFC and Prot A PFC induction. Thus, Tg-specific suppressor T cells are present in all normal subjects as part of the radiosensitive suppressor T cell subset. The increase in Tg-PFC caused by irradiation-induced inhibition of Tg-specific suppressor T cell function was significantly greater in normal subjects than in patients. Histamine type 2 receptor-bearing T cells inhibited Prot A PFC induction, but not Tg PFC induction, in the autologous T-B MC system. No Tg PFC were induced from normal B cells in any combination with untreated T cells, irradiated T cells, or histamine type 2 receptor-negative T cells from patients or normal subjects. These data indicate that in vitro Tg-specific T cell regulation can be studied in the T-B MC system by using B cells from patients with autoimmune thyroid disease with high Tg antibody titers in their sera. Tg-specific suppressor T cells appear to be present in all individuals and to be involved in the regulation of Tg antibody production. The lower activity of Tg-specific suppressor T cells in patients compared to that in normal subjects may be related to Tg antibody production in vivo. This abnormality, however, is heterogeneous and is not a complete but, rather, is a relative defect of Tg-specific suppressor T cells.

背景与目标： : 使用自身免疫性甲状腺疾病患者的淋巴细胞研究了甲状腺球蛋白斑块形成细胞 (Tg PFC) 和蛋白A斑块形成细胞 (Prot A PFC) 生成的T细胞调节。在没有促有丝分裂或抗原刺激的情况下进行T细胞和b细胞混合培养 (t-b MC)，以鉴定系统中的生理T细胞作用。在18例血清中甲状腺球蛋白抗体滴度较高的患者中，有8例 (44% 例) 发现了Tg PFC。在t-b MC系统中，使用这八名患者的b细胞研究了患者和正常受试者的T细胞对Tg的特异性和非特异性免疫调节。添加T细胞后，与Prot A PFC诱导相比，Tg PFC诱导值明显降低。正常T细胞抑制Tg PFC诱导，但患者T细胞不抑制，而通过添加患者和正常T细胞对Prot A PFC诱导发现了相同程度的辅助作用。来自患者和正常受试者的T细胞的照射 (1500 rads) 显着增强了TgPFC和Prot A PFC的诱导。因此，Tg特异性抑制T细胞作为放射敏感性抑制T细胞亚群的一部分存在于所有正常受试者中。在正常受试者中，由辐射诱导的Tg特异性抑制T细胞功能抑制引起的tg-pfc的增加明显大于患者。在自体t-b MC系统中，带有组胺2型受体的T细胞抑制Prot A PFC诱导，但不抑制Tg PFC诱导。正常b细胞与未经治疗的T细胞，辐照的T细胞或来自患者或正常受试者的组胺2型受体阴性T细胞的任何组合均未诱导Tg PFC。这些数据表明，可以使用来自血清中Tg抗体滴度较高的自身免疫性甲状腺疾病患者的b细胞，在t-b MC系统中研究体外Tg特异性T细胞调控。Tg特异性抑制T细胞似乎存在于所有个体中，并参与Tg抗体产生的调节。与正常受试者相比，患者中Tg特异性抑制T细胞的活性较低可能与体内Tg抗体的产生有关。然而，这种异常是异质的，不是完整的，而是Tg特异性抑制T细胞的相对缺陷。

BACKGROUND & AIMS: BACKGROUND:There are a growing number of observational studies that do not only focus on single biomarkers for predicting an outcome event, but address questions in a multivariable setting. For example, when quantifying the added value of new biomarkers in addition to established risk factors, the aim might be to rank several new markers with respect to their prediction performance. This makes it important to consider the marker correlation structure for planning such a study. Because of the complexity, a simulation approach may be required to adequately assess sample size or other aspects, such as the choice of a performance measure. METHODS:In a simulation study based on real data, we investigated how to generate covariates with realistic distributions and what generating model should be used for the outcome, aiming to determine the least amount of information and complexity needed to obtain realistic results. As a basis for the simulation a large epidemiological cohort study, the Gutenberg Health Study was used. The added value of markers was quantified and ranked in subsampling data sets of this population data, and simulation approaches were judged by the quality of the ranking. One of the evaluated approaches, the random forest, requires original data at the individual level. Therefore, also the effect of the size of a pilot study for random forest based simulation was investigated. RESULTS:We found that simple logistic regression models failed to adequately generate realistic data, even with extensions such as interaction terms or non-linear effects. The random forest approach was seen to be more appropriate for simulation of complex data structures. Pilot studies starting at about 250 observations were seen to provide a reasonable level of information for this approach. CONCLUSIONS:We advise to avoid oversimplified regression models for simulation, in particular when focusing on multivariable research questions. More generally, a simulation should be based on real data for adequately reflecting complex observational data structures, such as found in epidemiological cohort studies.

背景与目标：

BACKGROUND & AIMS: Context:Vitamin D deficiency patients have an increased cardiovascular (CV) morbidity and mortality. Carotid intima-media thickness (IMT) and carotid plaques are markers of subclinical atherosclerosis and predictors of CV events. Objective:To perform a meta-analysis of studies evaluating the impact of Vitamin D deficiency on common carotid artery IMT (CCA-IMT) and on the prevalence of carotid plaques. Data Sources:Studies were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. Results:Twenty-one studies (3,777 Vitamin D deficiency patients and 4,792 controls) with data on CCA-IMT and 6 studies (1,889 Vitamin D deficiency patients and 2,883 controls) on the prevalence of carotid plaques were included. Compared to controls, Vitamin D deficiency patients showed a significantly higher CCA-IMT (mean difference [MD]: 0.043 mm; 95%CI: 0.030, 0.056; P<0.001), and an increased prevalence of carotid plaques (Odds Ratio [OR]: 2.29, 95%CI: 1.03-5.11; P=0.043) with an attributable risk of 35.9%. When selecting studies specifically including patients with diabetes, the prevalence of carotid plaques in Vitamin D deficiency patients than in controls resulted higher (OR: 3.27; 95%CI: 1,62-6.62; P=0.001). A significant difference in CCA-IMT was confirmed when comparing patients with Vitamin D insufficiency to controls (MD: 0.011; 95%CI: 0.010-0.012, P<0.001). Sensitivity analyses substantially confirmed results and regression models showed that with the exception of LDL-cholesterol, HDL-cholesterol, triglycerides and the prevalence of hypercholesterolemia, all the other clinical and demographic co-variates significantly impacted on the difference in CCA-IMT between Vitamin D deficiency patients and controls. Conclusions:Both Vitamin D deficiency and Vitamin D insufficiency are associated with subclinical atherosclerosis, potentially suggesting an increased CV risk in these clinical settings.

背景与目标：

BACKGROUND & AIMS: :Menyanthes trifoliata L. is used in Swedish traditional medicine for the treatment of inflammatory diseases of the kidney, e.g. glomerulonephritis. Earlier studies have shown that MtL increases glomerular filtration rate after renal reperfusion ischemia. This activity was suggested to be PAF-inhibitory since MtL also inhibited PAF-induced exocytosis in vitro on human neutrophils (IC(50) = 0.16 mg/ml). The present study further characterizes the anti-inflammatory properties of a rhizome decoction of this plant. MtL inhibited carrageenan-induced rat paw edema (ID(50) ≈ 1.7 g/kg p.o.) and ethyl phenylpropiolate-induced rat ear edema (32% at 2.0 g/kg p.o.) in a dose-dependent manner. Further studies revealed that MtL inhibited both fMLP-induced exocytosis (IC(50) = 0.16 mg/ml) and elastase activity (IC(50) = 0.16 mg/ml). According to these results it is likely that the activity shown in the PAF-test is at least partly due to an inhibition of elastase. MtL showed only minor hemolytic properties at the concentrations used in the PAF- and fMLP-tests, suggesting that the cells in these tests are undamaged. The decoction also inhibited the biosynthesis of LTB(4) (IC(50) ≈ 0.73 mg/ml) and prostaglandins (IC(50) = 0.37 mg/ml) in vitro in a concentration-dependent way. However, at concentrations where the decoction is active in the LTB(4)-test, it also possesses hemolytic properties.

背景与目标： : Menyanthes trifoliata L.在瑞典传统医学中用于治疗肾脏的炎症性疾病，例如肾小球肾炎。较早的研究表明，MtL会增加肾脏再灌注缺血后的肾小球滤过率。该活性被认为是PAF抑制的，因为MtL还抑制了PAF诱导的人嗜中性粒细胞的胞吐作用 (IC(50) = 0.16 mg/ml)。本研究进一步表征了该植物根茎汤的抗炎特性。MtL以剂量依赖性方式抑制角叉菜胶诱导的大鼠爪子水肿 (ID(50) ≈ 1.7g/kg p.o.) 和苯基丙醇酸乙酯诱导的大鼠耳水肿 (32% 2.0g/kg p.o.)。进一步的研究表明，MtL抑制fMLP诱导的胞吐作用 (IC(50) = 0.16 mg/ml) 和弹性蛋白酶活性 (IC(50) = 0.16 mg/ml)。根据这些结果，PAF测试中显示的活性可能至少部分归因于弹性蛋白酶的抑制。在PAF和fMLP测试中使用的浓度下，MtL仅显示出较小的溶血特性，这表明这些测试中的细胞未受损。该汤剂还以浓度依赖性方式抑制体外LTB(4) (IC(50) ≈ 0.73 mg/ml) 和前列腺素 (IC(50) = 0.37 mg/ml) 的生物合成。然而，在汤在LTB(4)-测试中具有活性的浓度下，它也具有溶血特性。

BACKGROUND & AIMS: :The leaves of «moderately hardy» (spinach), «very hardy» (ivy) and «extremely hardy» (spruce) plants [classification according to Levitt {1980)] show characteristic differences with respect to changes in membrane lipid composition and chloroplast ultrastructure which are correlated with the degree of the frost resistance achieved by each type of tissue during adaptation to sub-zero temperatures. Spinach leaves showed no increase in their total lipid content upon frost hardening. On the contrary, the amount of galactolipids decreased considerably, whereas that of phospholipids only slightly increased. No shift from the saturated palmitic acid to the three-fold unsaturated linolenic acid was observed. The membrane lipid content of ivy leaves and spruce needles increased to a similar extent during frost hardening. However, in contrast to spruce needles, a distinct preferential accumulation of the phospholipids was observed in ivy leaves, resulting in an increased PL/GL ratio. A considerable shift from saturated (palmitic) to unsaturated fatty acids was detected in both plants, due mainly to an increase in the proportion of linoleic acid in ivy and of linolenic acid in spruce. In spite of the considerable increase in lipid content, no increase in chloroplast number per cell could be detected in ivy leaves, although the length of the thylakoids was nearly doubled and the plastids appeared to be in a division stage: however, no real division could ever be observed. On the contrary, an increase in the number of chloroplasts and mitochondria was observed in spruce needles. Membrane augmentation became further evident by the many large invaginations of the chloroplast envelope formed when the frost-hardened leaves of ivy or spruce were exposed to sub-zero temperatures which they could just survive.

背景与目标： : 中度耐寒 (菠菜) 的叶子，非常耐寒 (常春藤) 和极端耐寒 (云杉) 植物 [根据Levitt {1980分类] 在膜脂质组成和叶绿体超微结构的变化方面表现出特征差异，这与每种类型的组织在适应亚-零温度。菠菜叶在霜冻硬化后总脂质含量没有增加。相反，半乳糖脂的数量大大减少，而磷脂的数量仅略有增加。没有观察到从饱和棕榈酸到三倍不饱和亚麻酸的转变。在霜冻硬化期间，常春藤叶和云杉针的膜脂质含量增加到类似的程度。然而，与云杉针相反，在常春藤叶片中观察到磷脂的明显优先积累，导致PL/GL比增加。在两种植物中检测到从饱和 (棕榈酸) 到不饱和脂肪酸的相当大的转变，主要是由于常春藤中亚油酸和云杉中亚麻酸的比例增加。尽管脂质含量显着增加，但常春藤叶片中每个细胞的叶绿体数量没有增加，尽管类囊体的长度几乎增加了一倍，并且质体似乎处于分裂阶段: 但是，无法观察到真正的分裂。相反，在云杉针中观察到叶绿体和线粒体的数量增加。当常春藤或云杉的霜冻叶片暴露于零度以下的温度下，它们可以生存时，叶绿体包膜的许多大内陷就进一步明显增加了膜。

BACKGROUND & AIMS: :The cornea and the skin are both organs that provide the outer barrier of the body. Both tissues have developed intrinsic mechanisms that protect the organism from a wide range of external threats, but at the same time also enable rapid restoration of tissue integrity and organ-specific function. The easy accessibility makes the skin an attractive model system to study tissue damage and repair. Findings from skin research have contributed to unravelling novel fundamental principles in regenerative biology and the repair of other epithelial-mesenchymal tissues, such as the cornea. Following barrier disruption, the influx of inflammatory cells, myofibroblast differentiation, extracellular matrix synthesis and scar formation present parallel repair mechanisms in cornea and skin wound healing. Yet, capillary sprouting, while pivotal in proper skin wound healing, is a process that is rather associated with pathological repair of the cornea. Understanding the parallels and differences of the cellular and molecular networks that coordinate the wound healing response in skin and cornea are likely of mutual importance for both organs with regard to the development of regenerative therapies and understanding of the disease pathologies that affect epithelial-mesenchymal interactions. Here, we review the principal events in corneal wound healing and the mechanisms to restore corneal transparency and barrier function. We also refer to skin repair mechanisms and their potential implications for regenerative processes in the cornea.

背景与目标： : 角膜和皮肤都是提供身体外部屏障的器官。两种组织都已经开发出内在机制，可以保护生物体免受广泛的外部威胁，但同时也可以快速恢复组织完整性和器官特异性功能。易接近性使皮肤成为研究组织损伤和修复的有吸引力的模型系统。皮肤研究的发现有助于揭示再生生物学的新基本原理以及其他上皮间质组织 (例如角膜) 的修复。屏障破坏后，炎症细胞的流入，成肌纤维细胞的分化，细胞外基质的合成和疤痕的形成在角膜和皮肤伤口愈合中呈现平行的修复机制。然而，毛细血管发芽虽然在适当的皮肤伤口愈合中起着关键作用，但它与角膜的病理修复相当相关。了解协调皮肤和角膜伤口愈合反应的细胞和分子网络的平行和差异，对于再生疗法的发展和对影响上皮-间充质相互作用的疾病病理的理解，对于两个器官可能具有相互重要性。在这里，我们回顾了角膜伤口愈合的主要事件以及恢复角膜透明度和屏障功能的机制。我们还提到皮肤修复机制及其对角膜再生过程的潜在影响。

BACKGROUND & AIMS: :We have used a high-resolution small angle X-ray scattering system, together with a high-performance CCD camera, on the BioCAT beamline at the APS synchrotron radiation facility at the Argonne National Laboratory, to study X-ray interference effects in the meridional reflections generated by the arrays of myosin crossbridges in contracting muscle. These give information about axial movements of the myosin heads during contraction with sub-nanometer resolution. Using whole intact muscle preparations (frog sartorius) we have been able to record the detailed behavior of M3 (the first order meridional reflection from the myosin crossbridges, at 14.56 nm) at each of a number of quick releases of increasing magnitude, on the same specimen, and at the same time make similar measurements on higher order myosin meridional reflections, particularly M6. The latter provides information about the dispersion of lever arm angles of the actin-attached myosin heads. The observations show that in isometric contraction the lever arm angles are dispersed through +/- 20-25 degrees on either side of a mean orientation that is about 60 degrees away from their orientation at the end of the working stroke: and that they move towards that orientation in synchronized fashion, with constant dispersion, during quick releases. The relationship between the shift in the interference fringes (which measures the shift of the myosin heads scattering mass towards the center of the sarcomere, and the changes in the total intensity of the reflections, which measures the changes in the axial profile of the heads, is consistent with the tilting lever arm mechanism of muscle contraction. Significant fixed contributions to the meridional reflections come from unattached myosin heads and from backbone components of the myosin filaments, and the interaction of these with the contributions from actin-attached myosin heads determines the behavior of these reflections.

背景与目标： : 我们在阿贡国家实验室APS同步加速器辐射设施的BioCAT束线上使用了高分辨率小角度x射线散射系统以及高性能CCD相机，研究收缩肌肉中肌球蛋白交叉桥阵列产生的子午反射中的x射线干扰效应。这些以亚纳米分辨率提供了有关收缩过程中肌球蛋白头部轴向运动的信息。使用完整的完整肌肉制剂 (frog sartorius)，我们已经能够记录M3的详细行为 (肌球蛋白横桥的一阶子午反射，在14.56 nm处)，在相同的标本上，同时对高阶肌球蛋白子午反射，特别是m6进行类似的测量。后者提供了有关肌动蛋白附着的肌球蛋白头的杠杆臂角度分散的信息。观察结果表明，在等距收缩中，杠杆臂角在平均方向的两侧分散了20-25度，该方向在工作行程结束时与它们的方向相距约60度: 并且它们以同步方式向该方向移动，并具有恒定的色散，在快速释放期间。干涉条纹的位移 (测量肌球蛋白头部散射质量向肌节中心的位移) 与反射总强度的变化 (测量头部轴向轮廓的变化) 之间的关系，与肌肉收缩的倾斜杠杆臂机制一致。对子午反射的显着固定贡献来自未附着的肌球蛋白头和肌球蛋白细丝的骨干成分，而这些与肌动蛋白附着的肌球蛋白头的贡献的相互作用决定了这些反射的行为。

BACKGROUND & AIMS: :Affinity maturation of antibodies during the course of an adaptive immune response requires germinal centre (GC) formation within B-cell follicles. Much of the current understanding of GC function has been derived from histology, but these static views have left unresolved many questions about cell movement in GCs. In this Progress article, we describe how several recent studies using time-resolved multiphoton microscopy to track GC B-cell movement within lymph nodes have shed light on the processes that influence GC B-cell dynamics.

背景与目标： : 在适应性免疫反应过程中，抗体的亲和力成熟需要在b细胞卵泡内形成生发中心 (GC)。目前对GC功能的许多理解都来自组织学，但是这些静态观点留下了许多关于GCs中细胞运动的问题。在这篇进展文章中，我们描述了最近几项使用时间分辨多光子显微镜跟踪淋巴结内GC b细胞运动的研究如何揭示了影响GC b细胞动力学的过程。