Contributions of ion conductances to the onset responses of octopus cells in the ventral cochlear nucleus: simulation results

The onset response pattern displayed by octopus cells has been attributed to intrinsic membrane properties, low membrane impedance, and/or synaptic inputs. Although the importance of a low membrane impedance generally is acknowledged as an essential component, views differ on the role that ion channels play in producing the onset response. In this study, we use a computer model to investigate the contributions of ion channels to the responses of octopus cells. Simulations using current ramps indicate that, during the "ramp-up" stage, the membrane depolarizes, activating a low-threshold K(+) channel, K(LT), which increases membrane conductance and dynamically increases the current required to evoke an action potential. As a result, the model is sensitive to the rate that membrane potential changes when initiating an action potential. Results obtained when experimentally recorded spike trains of auditory-nerve fibers served as model inputs (simulating acoustic stimulation) demonstrate that a model with K(LT) conductance as the dominant conductance produces realistic onset response patterns. Systematically replacing the K(LT) conductance by a h-type conductance (which corresponds to a hyperpolarization-activated inward rectifier current, I(h)) or by a leakage conductance reduces the model's sensitivity to rate of change in membrane potential, and the model's response to "acoustic stimulation" becomes more chopper-like. Increasing the h-type conductance while maintaining a large K(LT) conductance causes an increase in threshold to both current steps and acoustic stimulation but does not significantly affect the model's sensitivity to rate of change in membrane potential and the onset response pattern under acoustic stimulation. These findings support the idea that K(LT), which is activated during depolarization, is the primary membrane conductance determining the response properties of octopus cells, and its dynamic role cannot be provided by a static membrane conductance. On the other hand, I(h), which is activated during hyperpolarization, does not play a large role in the basic onset response pattern but may regulate response threshold through its contribution to the membrane conductance.     

拟除虫菊酯浸泡大网孔门窗帘毒杀侵入实验小屋蚊虫的研究

本研究采用牛房实验小屋，加装不透光百叶窗和透光门廊，从而全面观察药帘对侵入实验小屋蚊虫毒杀情况，包括蚊虫入屋前接触药帘时和屋内蚊虫外逸出屋外后的死亡情况。结果表明，澳氰菊酯、二氯苯醚菊酯毒效强和持效长，浸泡门窗帘后６个月１８次试验，对侵入屋内蚊虫毒杀，平均死亡率分别为８９．４％和９０．６％。两药对入屋内蚊虫的吸血率均没有明显减少，可能与诱饵动物的吸引力有关。二氯苯醚菊酯有明显驱避作用，其减少蚊虫入屋率，按蚊为７０．６％，库蚊为７５．２％均没有明显减少，阿蚊却没有效应。     

The hypothalamus and the control of energy homeostasis: different circuits, different purposes.

The hypothalamus regulates many aspects of energy homeostasis, adjusting both the drive to eat and the expenditure of energy in response to a wide range of nutritional and other signals. It is becoming clear that various neural circuits operate to different degrees and probably serve specific functions under particular conditions of altered feeding behaviour. This review will discuss this functional diversity by illustrating hypothalamic neurones that express neuropeptide Y (NPY), the melanocortin-4 receptor (MC4-R) and the orexins. NPY neurones in the arcuate nucleus (ARC) release NPY, a powerful inducer of feeding and obesity, in the paraventricular nucleus (PVN) and the lateral hypothalamic area (LHA). ARC-NPY neurones are inhibited by leptin and insulin and become overactive when levels of these hormones fall during undernutrition. They may function physiologically to protect against starvation. With disruption of the inhibitory leptin signals due to gene mutations, the NPY neurones are overactive, which contributes to hyperphagia and obesity in the ob/ob and db/db mice and fa/fa Zucker rat. The MC4-R is activated by alpha-melanocyte-stimulating hormone [alpha-MSH; a cleavage product of pro-opiomelanocortin (POMC), which is expressed in the other ARC neurones] and inhibits feeding. This effect is antagonised by agouti gene-related peptide (AGRP), which is coexpressed by the ARC-NPY neurones only. Activation of MC4-R, possibly mediated by blockade of AGRP release, appears to restrain overeating of a palatable diet. This response may be programmed by a transient rise in leptin soon after presentation of palatable food, and rats that fail to do this will overeat and become obese. Orexin-A and -B (corresponding to hypocretins 1 and 2) are expressed in specific LHA neurones. These have extensive reciprocal connections with many areas involved in appetite control, including the nucleus of the solitary tracts (NTS), which relays vagal afferent satiety signals from the viscera. Orexin neurones also have close anatomical connections with LHA glucose-sensitive neurones. Orexin-A induces acute feeding but does not cause obesity. Orexin neurones are stimulated by hypoglycaemia partly via the NTS and inhibited by food ingestion. These neurones may therefore be involved in the severe hyperphagia of hypoglycaemia and short-term control of feeding.     

Evaluation of endothelial cell migration with a novel in vitro assay system

In this study we introduce a novel in vitro 'oil-drop' assay system for the measurement of endothelial cell (EC) migration, based on the original concept of the Teflon fence assay (Pratt et al., 1984; Am. J. Pathol. 117: 349–354). An aliquot of 15–20,000 human umbilical vein EC (HUVEC) is pipetted through a layer of mineral oil. The cells readily attach, spread and migrate on the surface of a matrix-coated tissue culture dish as a confluent circular monolayer. Migration is measured as the net increase in the total area covered at 24 hours. We have used this system to quantify EC migration on matrices composed of a mixture of type I collagen and either von Willebrand factor (vWF) or fibronectin (FN) in the presence or absence of tumor necrosis factor (TNF). Plating efficiency on both vWF/collagen and FN/collagen, measured by counting cells after attachment and spreading, is about 80%. With this method, migration on vWF/collagen was about 6.4 mm² and 5.3 mm² for TNF-treated and untreated HUVEC, respectively. HUVEC migration on FN/collagen was slightly greater – 6.4 mm² and 6.5 mm² with and without TNF treatment, respectively. During the 24 hour time period, HUVEC numbers increased 30–40% on vWF/collagen, and 60–80% on FN/collagen, with increased proliferation observed with TNF- treatment. EC proliferation could be completely inhibited by 2 mM hydroxyurea. This assay system has proven useful in our studies to quantify cell migration and proliferation.     

人表皮郎格罕细胞Birbeck颗粒的超微结构观察

本文对正常人表皮郎格罕细胞MBirbeck颗粒(LG)怍了超微结构观察。计数十个细胞中146个LG的各种切面形态和出现频率,结果为:杆状占53.4％,球拍状占8.2％,泡状占7.5％,弧状占15％,环状占11％,同号状占4.8％六种。LG长约100-500nm,杆部宽为40-50nm,泡直径为70-350nm,环状的环厚为25-50am。本结果提示LG的本体结构除扁盘状和扁盘泡状外,还可能存在扁盘杯状的立体模式。     

Structure and diversity of class I antigen presenting molecules in the mouse

Sequence comparisons among class I genes provide insight into the nature and origins of diversity in the human and mouse MHC. The profiles of diversity among alleles and between different loci indicate that genetic interactions among class I genes generate sequence diversity in both species. Humans and mice differ in the extent that sequence transfer occurs between loci. In mice, sequences encoding the antigen binding domain show little evidence of locus specificity. A series of mouse class I mutants have been analyzed, providing strong evidence that interlocus gene conversion plays a significant role in the exchange of sequences among class I genes. A similar process is suspected in human class I and both mouse and human class II genes. However, the transfer of sequence among genes in these groups appears to occur predominantly between alleles and only to a minor extent between loci.     

Tissue-specific homing receptor mediates lymphocyte adhesion to cytokine-stimulated lymph node high endothelial venule cells.

Lymphocytes bind to high endothelial venule (HEV) cells as the first step in the migration of these cells into lymph nodes (LN) and Peyer's patches (PP). In this study we isolated and cultured HEV cells from rat LN and investigated the effects of cytokines on the adhesiveness of these cells for lymphocytes. The results showed that lymphocytes from thoracic duct, spleen and LN adhered preferentially to the cultured LN HEV cells compared to cells isolated from the thymus and bone marrow. The adhesiveness of LN HEV cells for thoracic duct lymphocytes (TDL) was significantly increased in a dose- and time-dependent manner by pretreatment of the HEV cells with tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) or interleukin-4 (IL-4). In contrast, pretreatment of HEV cells with IL-1, IL-6 or IL-7 did not alter the capacity of LN HEV cells to adhere lymphocytes. Furthermore, incubation of LN HEV cells with suboptimal doses of TNF and IL-4, IFN-gamma and IL-4, or TNF-alpha and IFN-gamma increased significantly the endothelial adhesiveness. Interestingly, although IL-1 alone did not promote the adhesiveness of HEV cells, the cytokine synergized with suboptimal doses of IL-4 and TNF-alpha to increase the adhesiveness. The adhesion of TDL to non-stimulated and IL-4-stimulated LN HEV cells could be blocked specifically by treatment of lymphocytes with the LN homing-receptor-specific A.11.5 monoclonal antibody (mAb). In contrast, lymphocytes pretreated with the PP-homing receptor-specific 1B.2.6 mAb or the antileucocyte common antigen (OX1) mAb adhered normally to the HEV cells. Taken together, these results indicate that the baseline and cytokine-stimulated bindings between lymphocytes and LN HEV cells are mediated by adhesive mechanisms that regulate lymphocyte migration into LN in vivo and provide strong evidence that cytokines are central mediators of organ-specific lymphocyte migration.     

Microcirculation in the upper trapezius muscle during varying levels of static contraction,fatigue and recovery in healthy women —a study using percutaneous laser-Doppler flowmetry and surface electromyography

Summary Microcirculation in the upper portion of the trapezius muscle was measured percutaneously by continuous laser-Doppler flowmetry (LDF) during two 10-min series of alternating 1-min periods of static contraction and rest determined electromyographically (EMG). Stepwise increased contraction was induced by keeping the arms straight and elevated at 30, 60, 90 and 135°, which was repeated with a 1-kg load carried in each hand. Thereafter, fatigue and recovery were recorded while the subject kept her arms straight and elevated at 45° carrying the 1-kg hand load as long as possible, followed by rest with arms hanging and no load. A group of 16 healthy women of different ages was studied. Signal processing was done on line using a 386 SX computer. The LDF- and root-mean-square (rms) EMG signals were normalized. Spectrum analyses of EMG mean power frequency (MPF) and median spectrum frequency were performed. The rms-EMG increased significantly with an increase in the calculated shoulder torque (r=0.75). Accumulated local fatigue was indicated by a decrease in MPF with increased shoulder angle and added load (r = –0.54). Blood flow increased with increased shoulder angle (r=0.82, with hand loadr=0.62) and with increased shoulder torque (r=0.72), and also showed a significant increase with increased EMG activity (r=0.74). The LDF showed a negative correlation to MPF (r= –0.67), with increased values when MPF was lowered. During the endurance test, a moderate increase of LDF occurred which reached its maximum during the 1st min of recovery. Then, a slow return to the base level was recorded. The ability to increase the flow in the microcirculation with increasing muscle load was not diminished with age.