Antigens targeted to the Leishmania phagolysosome are processed for CD4+ T cell recognition

Processing of antigen for recognition by class II-restricted CD4⁺ T cells occurs within acidic compartments of the antigen-presenting cell. The exact nature of this compartment has yet to be precisely defined, however, but may vary depending upon the cell type studied and the antigen used. The acidic compartments of macrophages are also responsible for the degradation of ingested micro-organisms and play host to others which are adapted to an intracellular existance. To determine whether the phagolysosome (PL) formed in activated macrophages after ingestion of Leishmania parasites is also a site for entry of antigen into the class II presentation pathway, we have used the approach of genetic transformation. Hence, Leishmania were transfected with the genes for the protein antigens ovalbumin (OVA) and β-galactosidase (β-gal) and after infection were able to deliver these antigens specifically into the PL. Delivery of antigen to this site resulted in the ability of infected macrophages to present these antigens to antigen-specific CD4⁺ T cells. After taking into account the absolute levels of antigen uptake by macrophages, a 4-h processing period for OVA delivered by this or a soluble route led to equivalent levels of T cell activation. Unlike macrophages pulsed with soluble OVA, those with PL-targeted OVA still retained the ability to stimulate T cells after a 24-h processing period. This enhanced lifespan of antigen in macrophages corresponded to the kinetics of degradation of the parasite, suggesting slow release of antigen into the processing pathway. β-gal presentation from the PL was tenfold less efficient under the same conditions. In addition to providing the first information on antigen processing in a protozoan PL, these studies highlight the usefulness of genetically transformed parasites for these types of studies.     

SUMO化修饰:一种多功能的蛋白质翻译后修饰方式

SUMO分子是一种结构上与泛素相似的分子,它参与蛋白质翻译后修饰。SUMO化循环与泛素化循环过程相似,但SUMO化修饰具有与泛素化修饰截然不同的功能。泛素化修饰的靶分子主要被蛋白酶体降解,而SUMO化修饰则介导靶分子定位和功能调节。新近发现SUMO化修饰参与调控线粒体分裂、DNA损伤修复及调节基因组稳定性、调控离子通道及生物节律。此外,SUMO化修饰功能的紊乱会导致某些疾病的发生。     

Genes encoded in the major histocompatibility complex affecting the generation of peptides for TAP transport

The B cell line 721.174 has lost the ability to present intracellular antigens to major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL). This phenotype results from a homozygous deletion in the MHC that includes the peptide transporter genes TAP1 and TAP2, and the proteasome subunits LMP2 and LMP7. Recent work has shown that such cells transfected with TAP genes load their class I molecules with endogenous peptides, and present several viral epitopes to class I-restricted CTL. These data implied that the LMP2 and LMP7 genes were not required for the presentation of most epitopes through class I molecules. By contrast, while confirming the previous reports, we have identified several epitopes that appear to require genes in the MHC in addition to the TAP for their presentation. Further analysis localizes the defect to proteolysis in the cytosol. In one case, presentation could be partially restored by re-expression of full-length LMP7. Control experiments with LMP7, from which the putative pro-region had been removed, failed to restore presentation, and this lack of effect correlated with failure of the shortened LMP7 to incorporate into the proteasome. These results suggest a role for LMP7 in the generation of a viral epitope, but leave open the possibility that additional genes within the .174 deletion are required for full restoration of antigen presentation.     

Dopaminergic agents differentially alter β-endorphin processing patterns in the rat pituitary neurointermediate lobe

We have established the content and molecular species of immunoreactive β-endorphin (ir-β-END) and immunoreactive N-acetyl-endorphin (ir-Nac-END) in rat neurointermediate lobe by specific radioimmunoassay (RIA) and high-performance liquid chromatography after chronic administration of dopamine (DA) agonists and antagonists. The DA agonist, bromocriptine, reduces tissue levels of all major immunoreactive species, in particular the C-terminally shortened N-acetylated forms. The DA antagonist, haloperidol, proportionally increases all immunoreactive forms, except Nac-β-END_1–27, thus altering the relative abundance of this species. These data indicate that DA is involved in the control of both tissue levels and processing of β-END-like peptides in the rat neurointermediate lobe.     

Distributed cortical networks for focused auditory attention and distraction

We used behavioral measures and functional magnetic resonance imaging (fMRI) to study the effects of parametrically varied task-irrelevant pitch changes in attended sounds on loudness-discrimination performance and brain activity in cortical surface maps. Ten subjects discriminated tone loudness in sequences that also included infrequent task-irrelevant pitch changes. Consistent with results of previous studies, the task-irrelevant pitch changes impaired performance in the loudness discrimination task. Auditory stimulation, attention-enhanced processing of sounds and motor responding during the loudness discrimination task activated supratemporal (auditory cortex) and inferior parietal areas bilaterally and left-hemisphere (contralateral to the hand used for responding) motor areas. Large pitch changes were associated with right hemisphere supratemporal activations as well as widespread bilateral activations in the frontal lobe and along the intraparietal sulcus. Loudness discrimination and distracting pitch changes activated common areas in the right supratemporal gyrus, left medial frontal cortex, left precentral gyrus, and left inferior parietal cortex.     

Error-related brain potentials are differentially related to awareness of response errors: evidence from an antisaccade task

The error negativity (Ne/ERN) and error positivity (Pe) are two components of the event-related brain potential (ERP) that are associated with action monitoring and error detection. To investigate the relation between error processing and conscious self-monitoring of behavior, the present experiment examined whether an Ne and Pe are observed after response errors of which participants are unaware. Ne and Pe measures, behavioral accuracy, and trial-to-trial subjective accuracy judgments were obtained from participants performing an antisaccade task, which elicits many unperceived, incorrect reflex-like saccades. Consistent with previous research, subjectively unperceived saccade errors were almost always immediately corrected, and were associated with faster correction times and smaller saccade sizes than perceived errors. Importantly, irrespective of whether the participant was aware of the error or not, erroneous saccades were followed by a sizable Ne. In contrast, the Pe was much more pronounced for perceived than for unperceived errors. Unperceived errors were characterized by the absence of posterror slowing. These and other results are consistent with the view that the Ne and Pe reflect the activity of two separate error monitoring processes, of which only the later process, reflected by the Pe, is associated with conscious error recognition and remedial action.     

New computed radiography using scanning laser stimulated luminescence

Summary This short paper summarizes the basic concept and the technology of a new computed radiographic system which uses an energy-storage phosphorus panel called Imaging Plate as an image sensor. The Imaging Plate can be used to obtain radiographs in exactly the same way as the screen-film combination is used in conventional radiography. The system eliminates the drawbacks of conventional screen-film radiography by combining digital image processing and digitization of the x-ray energy pattern utilizing scanning laser stimulated luminescence.The major part of this paper was originally delivered at the 1984 AAPM Annual Summer School which was held on July 22–27 at University of Notre Dame, USA. Modified for the publication in the Neurosurgical Review.     

经典名方中杜仲的本草考证

通过查阅历代本草、医籍、方书并结合近现代文献资料,笔者对杜仲药材的名称、基原、产地、品质评价、采收加工、炮制历史沿革及产地变迁情况进行了系统梳理及考证,以期为含杜仲的经典名方开发提供参考依据。经考证可知,历代本草均以杜仲为正名,基原为杜仲科植物杜仲Eucommia ulmoides的干燥树皮,古今一致;杜仲最早的产地为河南、山西、陕西、四川一带,自明代以来产地扩展至全国大部分地区,且推崇四川、陕西、重庆、贵州、湖北等地为杜仲的道地产区;近代以来总结其品质以皮厚、块大、粗皮刮净、断面多丝、内表面色暗紫为佳;杜仲的古代炮制加工方法主要有去粗皮切制生用和加酥蜜、姜汁、盐水、酒等辅料炮制,近现代以来炮制方法日趋简化,沿用的炮制方法主要为净制后切制生用、盐炙,建议挖掘不同杜仲炮制品的现代科学内涵,通过标准恢复传统主流炮制方法。基于宋代陈自明的三痹汤中杜仲“去皮,切,姜汁炒”的要求,根据考证结果,建议使用姜杜仲,即参考2020年版《中华人民共和国药典》炒法,以姜汁为辅料进行炮制后入药。     

Resistant Starch Production and Glucose Release from Pre‐Prepared Chilled Food: The SPUD Project

With an increasing prevalence of diabetes worldwide, effective dietary strategies for blood glucose control are crucial. As carbohydrates make up approximately 50% of the diet, it is neither practical nor advisable to avoid them altogether. Most of the carbohydrate in the diet is derived from starch, found in potatoes, pasta, rice and bread. These foods are often processed in some way before consumption, yet little is known about the effects processing, such as chilling and reheating, has on the glycaemic response, particularly when the food is consumed in the context of a mixed meal. This article introduces the SPUD project, a BBSRC DRINC‐funded initiative. Taking the potato as the model carbohydrate, this project will investigate, via in vitro and in vivo studies, the effects of domestic food processing techniques on the glycaemic response. A final study, utilising intrinsically labelled potato and a dual stable isotope methodology, will model glucose flux data to determine the underlying mechanisms of action.     

光纤化学传感器—计算机联用实时在位测定氧氟沙星片体外溶出度

目的：探索一种连续在位测定固体制剂溶出度的新方法和新理论。方法：应用芘丁酸光纤化学传感器和计算机联用在线技术及中国药典（1995版）规定的紫外分光光度法（UV）分别测定氧氟沙星片剂的体外溶出度。结果：在药典规定的测定浓度范围内有良好的线性,相关系数0．9980。方法的日内、日间精密度（RSD）分别为1．18％和1．56％,当信噪比为3时检测限为0．56μg/ml。用中国药典（1995版）规定的紫外分光光度法作对照并进行评价,P＞0．05,显示两种方法所得结果无显著性差异。结论：本法改变传统的取样分析模式,实现了响应快速、准确、灵敏的过程分析。