Development and selection of γδ T cells

Summary:  Two main lineages of T cells develop in the thymus: those that express the αβ T-cell receptor (TCR) and those that express the γδ TCR. Whereas the development, selection, and peripheral localization of newly differentiated αβ T cells are understood in some detail, these processes are less well characterized in γδ T cells. This review describes research carried out in this laboratory and others, which addresses several key aspects of γδ T-cell development, including the decision of precursor cells to differentiate into the γδ versus αβ lineage, the ordered differentiation over the course of ontogeny of functional γδ T-cell subsets expressing distinct TCR structures, programming of ordered Vγ gene rearrangement in the thymus, including a molecular switch that ensures appropriate Vγ rearrangements at the appropriate stage of development, positive selection in the thymus of γδ T cells destined for the epidermis, and the acquisition by developing γδ T cells of cues that determine their correct localization in the periphery. This research suggests a coordination of molecularly programmed events and cellular selection, which enables specialization of the thymus for production of distinct T-cell subsets at different stages of development.     

Das Magengeschwür als energiebilanzproblem: Entwurf eines cellularen automaten zur simulation von verteilungsstörungen der magenwanddurchblutung

Zusammenfassung Ein cellularer Automat, der eine vereinfachte Abschätzung von Verteilungsmustern der Magendurchblutung erlaubt, wird beschrieben. Die auf der Basis des Energiebedarfs der Säuresekretion und der Morphologie der Magenstrombahn simulierbaren Umverteilungsphänomene stimmen in Form und Lage mit dem menschlichen Magengeschwür überein. Sonderfälle der peptischen' Läsion, wie das lineare Geschwür oder die peptische' Stenose der Speiseröhre, sind mit der Theorie des submucösen Steal-Phänomens zu vereinbaren.

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Gastric ulcer as a problem of energy balance: Design of a cellular automaton for simulation of disorders of blood flow distribution to the stomach wall

Summary A cellular automaton is described, which allows a simple simulation of patterns of gastric blood flow distribution. Effects of redistribution, which can be simulated on the basis of the energy requirements of acid secretion and the morphology of the gastric vascular bed, are isomorph to form and site of gastric ulcer in man. Special forms of the peptic lesion as linear ulcers or peptic stenoses of the oesophagus are consistent with the theory of a submucous steal-phenomenon.

Herrn Prof. Dr. Dr. rer. nat. h. c. Friedrich Stelzner zum 65. Geburtstag gewidmet     

某钢丝绳生产企业职业危害现状调查及控制对策

目的了解某钢丝绳生产企业职业病危害现状,为控制该企业职业病危害因素提供依据。方法通过对某钢丝绳生产企业进行职业卫生现场调查、职业病危害因素检测,收集有关数据和资料,结合职业病危害防护设施、个人职业病危害防护、应急救援措施、职业健康检查结果等进行分析评价。结果粉尘、毒物、高温检测结果均符合国家职业卫生标准,合绳捻股车间捻股机、合绳机岗位噪声强度检测结果超标率100%,拉丝车间噪声检测合格率16.7%。职业卫生管理措施不够完善。结论该公司属于职业病危害较重企业,劳动者有发生职业性慢性铅中毒、职业性化学性灼伤、职业性噪声聋的风险,需采取有效措施进行整改。     

基于转录组信息的甘松MADS-box转录因子家族分析

目的 基于转录组数据筛选鉴定分析甘松Nardostachys jatamansi MADS-box转录因子家族。方法 利用生物信息学的方法全面分析甘松MADS-box基因家族成员的蛋白理化性质、亚细胞定位、基因结构、导肽、信号肽及跨膜结构域、系统进化树。结果 在甘松转录组数据中共鉴定出20个MADS-box转录因子,含有90～365个氨基酸,相对分子质量在10 179.96～41 707.68,理论等电点范围为4.87～10.43,主要在细胞核表达,均含有MADS保守结构域,均不含信号肽、导肽以及跨膜结构域。系统发育分析表明甘松MADS蛋白主要属于TypeII型。结论 利用生物信息学分析手段,鉴定了甘松MADS-box家族转录因子,为甘松深入研究甘松MADS-box蛋白的生物学功能提供参考,为甘松的药用成分合成调控机制提供研究基础,为培育优质甘松新品种提供依据。     

Randomized controlled trial comparing magnetic marker localization (MaMaLoc) with wire-guided localization in the treatment of early-stage breast cancer

Wire-guided localization (WGL) is the standard of care in the surgical treatment of nonpalpable breast tumors. In this study, we compare the use of a new magnetic marker localization (MaMaLoc) technique to WGL in the treatment of early-stage breast cancer patients. Open-label, single-center, randomized controlled trial comparing MaMaLoc (intervention) to WGL (control) in women with early-stage breast cancer. Primary outcome was surgical usability measured using the System Usability Scale (SUS, 0–100 score). Secondary outcomes were patient reported, clinical, and pathological outcomes such as retrieval rate, operative time, resected specimen weight, margin status, and reoperation rate. Thirty-two patients were analyzed in the MaMaLoc group and 35 in the WGL group. Patient and tumor characteristics were comparable between groups. No in situ complications occurred. Retrieval rate was 100% in both groups. Surgical usability was higher for MaMaLoc: 70.2 ± 8.9 vs. 58.1 ± 9.1, p < 0.001. Patients reported higher overall satisfaction with MaMaLoc (median score 5/5) versus WGL (score 4/5), p < 0.001. The use of magnetic marker localization (MaMaLoc) for early-stage breast cancer is effective and has higher surgical usability than standard WGL.     

Embryonic development of four different subsets of cholinergic neurons in rat cervical spinal cord

The developmental stage at which a neuron becomes committed to a neurotransmitter phenotype is an important time in its ontogenetic history. The present study examines when choline acetyltransferase (ChAT) is first detected within each of four different subsets of cholinergic neurons previously identified in the cervical enlargement of the spinal cord: namely, motor neurons, partition cells, central canal cluster cells, and dorsal horn neurons. By examining the temporal sequence of embryonic development of these cholinergic neurons, we can infer the relationships between ChAT expression and other important developmental events. ChAT was first detected reliably on embryonic day 13 (E13) by both biochemical and immunocytochemical methods, and it was localized predominantly within motor neurons. A second group of primitive-appearing ChAT-positive cells was detected adjacent to the ventricular zone on E14. These neurons seemed to disperse laterally into the intermediate zone by E15, and, on the basis of their location, were tentatively identified as partition cells. A third group of primitive ChAT-immunoreactive cells was detected on E16, both within and around the ventral half of the ventricular zone. By E17, some members of this "U"-shaped group appeared to have dispersed dorsally and laterally, probably giving rise to dorsal horn neurons as well as dorsal central canal cluster cells. Other members of this group remained near the ventral ventricular zone, most likely differentiating into ventral central canal cluster cells. Combined findings from the present study and a previous investigation of neurogenesis (Phelps et al.: J. Comp. Neurol. 273:459-472, '88), suggest that premitotic precursor cells have not yet acquired the cholinergic phenotype because ChAT is not detectable until after the onset of neuronal generation for each of the respective subsets of cholinergic neurons. However, ChAT is expressed in primitive bipolar neurons located within or adjacent to the germinal epithelium. Transitional stages of embryonic development suggest that these primitive ChAT-positive cells migrate to different locations within the intermediate zone to differentiate into the various subsets of mature cholinergic neurons. Therefore, it seems likely that spinal cholinergic neurons are committed to the cholinergic phenotype at pre- or early migratory stages of their development. Our results also hint that the subsets of cholinergic cells may follow different migration routes. For example, presumptive partition cells may use radial glial processes for guidance, whereas dorsal horn neurons may migrate along nerve fibers of the commissural pathway. Cell-cell interactions along such diverse migratory pathways could play a role in determining the different morphological, and presumably functional, phenotypes expressed by spinal cholinergic neurons.     

The regulation by phosphorylation of ‘priming' of phospholipase A2 activity in the neutrophil model system,differentiated HL60 cells

1. Differentiated HL60 cells have been utilized as a model system to examine the ‘priming'' of neutrophil phospholipase A₂ activity. In control cells activation of phospholipase A₂ by a 5 min stimulation with the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (100 nM) was essentially undetectable. When cells were primed by preincubation with 5 μM cytochalasin B for 5 min arachidonate release, a measure of phospholipase A₂ activation, was observed within 20 s.
2. Priming by cytochalasin B did not involve or require a change in intracellular free calcium concentration.
3. Priming was associated with an increase in general protein tyrosine phosphorylation and could also be induced by the receptor tyrosine kinase agonist granulocyte macrophage colony-stimulating factor (GM-CSF, 20 ng ml⁻¹) and be mimicked by treatment with the phosphotyrosine phosphatase inhibitor perhydrovanadate (0.5 mM). However, an increase in MAP kinase activity was not involved in the priming process.
4. Western blot analysis demonstrated that phospholipase A₂ was phosphorylated in both control and primed cells, but that an increase in the amount of membrane associated enzyme was found in the primed cells.
5. Thus priming appears to be due to membrane association of the phospholipase and this may be regulated by tyrosine kinase activities.

     

Haptic localization and the internal representation of the hand in space

As the hand actively explores the environment, contact with an object leads to neuronal activity in the topographic maps of somatosensory cortex. However, the brain must combine this somatotopically encoded tactile information with an internal representation of the hand's location in space if it is to determine the position of the object in three-dimensional space (3-D haptic localization). To investigate the fidelity of this internal representation in human subjects, a small tactual stimulator, light enough to be worn on the subject's hand, was used to present a brief mechanical pulse (6-ms duration) to the right index finger before, during, or after a fast, visually evoked movement of the right hand. In experiment 1, subjects responded by pointing to the perceived location of the mechanical stimulus in 3-D space. Stimuli presented shortly before or during the visually evoked movement were systematically mislocalized, with the reported location of the stimulus approximately equal to the location occupied by the hand 90 ms after stimulus onset. This pattern of errors indicates a representation of the movement that fails to account for the change in the hand's location during somatosensory delays and, in some subjects, inaccurately depicts the velocity of the actual movement. In experiment 2, subjects were instructed to verbally indicate the perceived temporal relationship of the stimulus and the visually evoked movement (i.e., by reporting whether the stimulus was presented before, during, or after the movement). On average, stimuli presented in the 38-ms period before movement onset were more likely to be perceived as having occurred during rather than before the movement. Similarly, stimuli in the 145-ms period before movement termination were more likely to be perceived as having occurred after rather than during the movement. The analogous findings of experiments 1 and 2 indicate that the same inaccurate representation of dynamic hand position is used to both localize tactual stimuli in 3-D space and construct the perception of arm movement.