Neural responses in primary auditory cortex mimic psychophysical, across-frequency-channel, gap-detection thresholds

Responses of single- and multi-units in primary auditory cortex were recorded for gap-in-noise stimuli for different durations of the leading noise burst. Both firing rate and inter-spike interval representations were evaluated. The minimum detectable gap decreased in exponential fashion with the duration of the leading burst to reach an asymptote for durations of 100 ms. Despite the fact that leading and trailing noise bursts had the same frequency content, the dependence on leading burst duration was correlated with psychophysical estimates of across frequency channel (different frequency content of leading and trailing burst) gap thresholds in humans. The duration of the leading burst plus that of the gap was represented in the all-order inter-spike interval histograms for cortical neurons. The recovery functions for cortical neurons could be modeled on basis of fast synaptic depression and after-hyperpolarization produced by the onset response to the leading noise burst. This suggests that the minimum gap representation in the firing pattern of neurons in primary auditory cortex, and minimum gap detection in behavioral tasks is largely determined by properties intrinsic to those, or potentially subcortical, cells.     

Sequential activation of Rap1 and Rac1 small G proteins by PDGF locally at leading edges of NIH3T3 cells

Moving cells form protrusions, such as filopodia and lamellipodia, and focal complexes at leading edges, which eventually enhance cell movement. The Rho family small G proteins, Rac1, Cdc42 and RhoA, are involved in the formation of these leading edge structures. We investigated the role of another small G protein Rap1 in the platelet-derived growth factor (PDGF)-induced formation of leading edge structures and cell movement. Upon stimulation of NIH3T3 cells by PDGF, leading edge structures were formed and Necl-5, integrin α_Vβ₃, and PDGF receptor were accumulated at leading edges. Rap1, upstream regulators of Rap1 such as Crk and C3G, and a downstream effector RalGDS, were accumulated at peripheral ruffles over lamellipodia. Over-expression of Rap1GAP, which inactivates Rap1, and knockdown of Rap1 inhibited the PDGF-induced formation of leading edge structures, accumulation of these molecules, and cell movement. In addition, Rap1 activation subsequently induced accumulation of Rac1, Vav2 and PAK at peripheral ruffles, which was inhibited by Rap1GAP and knockdown of Rap1. These results indicate that Rap1, activated by PDGF, is recruited to leading edges and that Rac1 is thereby activated locally at peripheral ruffles. This process is pivotal for the PDGF-induced formation of leading edge structures and cell movement.     

Necl-5/PVR enhances PDGF-induced attraction of growing microtubules to the plasma membrane of the leading edge of moving NIH3T3 cells

Microtubules (MTs) search for and grow toward the leading edge of moving cells, followed by their stabilization at a specific structure at the rear site of the leading edge. This dynamic re-orientation of MTs is critical to directional cell movement. We previously showed that Necl-5/poliovirus receptor (PVR) interacts with platelet-derived growth factor (PDGF) receptor and integrin α(v) β(3) at the leading edge of moving NIH3T3 cells, resulting in an enhancement of their directional movement. We studied here the role of Necl-5 in the PDGF-induced attraction of growing MTs to the leading edge of NIH3T3 cells. Necl-5 enhanced the PDGF-induced growth of MTs and attracted them near to the plasma membrane of the leading edge of NIH3T3 cells in an integrin α(v) β(3) -dependent manner. Furthermore, Necl-5 enhanced the PDGF-induced attraction of the plus-end-tracking proteins (+TIPs), including EB1, CLIP170, an intermediate chain subunit of cytoplasmic dynein, and p150(Glued) , a subunit of dynactin, near to the plasma membrane of the leading edge. Thus, Necl-5 plays a role in the attraction of growing MTs to the plasma membrane of the leading edge of moving cells.     

HCG注射日卵泡大小对体外授精-胚胎移植妊娠率的影响

目的探讨体外受精-胚胎移植（in vitro fertilization and embryo transfer,IVF-ET）的COS周期中HCG给予日卵泡大小对妊娠率的影响。方法将467IVF/ICSI-ET周期中HCG日最大卵泡径线大小分为A组（〈16mm）、B组（16.5-17.5mm）、C组（18-19mm）、D组（≥19.5mm）,分析其妊娠结局、获卵数、子宫内膜厚度与可利用胚胎数。结果各组妊娠率分别为：A组25%,B组32.1%,C组30.5%,D组26.1%,有显著差异（P≤0.05）,获卵数差异有显著性,子宫内膜厚度比较无显著差异。结论体外授精-胚胎移植COS周期中,主导卵泡在16.5-19mm时决定给予HCG妊娠率较高。     

Molecular defects in hormone receptors and G proteins in human disorders

The biological effects of hormones are mediated by plasma membrane and nuclear receptors which transmit extracellular signals to the cytoplasm and nucleus. The mutations in these receptors can affect normal signal transduction with loss-of-function mutations leading to hormone resistance and gain-of-function mutations leading to constitutive activation of signaling pathways. Mutations in plasma membrane are involved in a large number of clinical disorders, including dwarfism, Laron syndrome, congenital hyperthyroidism or hypothyroidism, nephrogenic diabetes insipidus, resistance to TSH, LH, FSH and ACTH, Jansen's metaphyseal chondrodysplasia and autosomal dominant hypoparathyroidism. While, mutations in nuclear receptors are the cause of resistance to glucocorticoid, androgen, estrogen, thyroid hormone and vitamin D. The loss-of-function mutations leading to familial hormone resistance disorders are germ line in origin whereas the gain-of-function mutations leading to constitutively active receptors are somatic. The plasma membrane receptors for those disorders except GH resistance consist of seven spanning-transmembranes which couple with GTP binding (G) protein. Abnormal G protein also exhibits gain and loss of function for hormones, leading to tumors and pseudo-hypoparathyroidism, respectively. This review summarizes molecular defects in hormone receptors and G proteins and their associated clinical features.     

Effects of Visual Environment Complexity on Saccade Performance in Humans with Different Functional Asymmetry Profiles

Studies in 47 right-handed subjects with right and left leading eyes addressed the latent periods of visually-evoked saccades in the horizontal, vertical, and diagonal directions within the field of vision. Visual environments with three levels of temporospatial complexity and two standard time protocols of visual stimulation, with “gap” and “overlap,” were used. In subjects with left leading eyes, saccades were more often performed with shorter latent periods in the direction ipsilateral to the leading eye than in the contralateral direction (53% versus 20%); among subjects with right leading eyes, the proportions with decreases in the latent periods in the ipsi- and contralateral directions were different (25% and 22%, respectively). Thus, there was a relationship between eye dominance and the spatial asymmetry of the latent periods of saccades.     

Oxidative stress, lipid rafts, and macrophage reprogramming

Oxidant stress, induced under a variety of conditions, is known to lead to the molecular reprogramming of the tissue-fixed macrophage. This reprogramming is associated with an altered response to subsequent inflammatory stimuli, such as lipopolysaccharide (LPS), leading to enhanced liberation of proinflammatory chemokines and cytokines. Due to this altered response, dysregulated immunity ensues, leading to the development of clinical syndromes such as multiple organ dysfunction syndrome (MODS). Although the mechanisms responsible for this altered macrophage activity by oxidant stress remains complex and poorly elucidated, it appears, based on recent research, that early and direct alterations within lipid rafts are responsible. This early and direct interaction with lipid rafts by oxidants leads to the mobilization of annexin VI from lipid raft constructs, leading to the release of calcium. This increased cytosolic concentration of this secondary messenger, in turn, results in the activation of calcium-dependent kinases, leading to further alterations in lipid raft lipids and eventually lipid raft proteins. Due to these lipid raft compositional changes, preassembly of receptor complexes occur, leading to enhanced proinflammatory activation. Within this review, the complexity of oxidant-induced reprogramming within the tissue fixed macrophage as currently understood is explained.     

Ultrastructural study of TPA-induced cell motility: human well-differentiated rectal adenocarcinoma cells move as coherent sheets via localized modulation of cell-cell adhesion

We previously found that 12-O-tetradecanoylphorbol-13-acetate (TPA)-enhanced invasion of Matrigel was associated with augmentation of cell motility but not with metalloproteinase activity in a highly metastatic variant (L-10) of human rectal adenocarcinoma cell line RCM-1. In a two-dimensional cell motility assay, TPA induced active L-10 cell locomotion with characteristic morphology; the cells moved outwards from the cell islands mainly as a localized coherent sheet of cells. The leading cells showed locomotor morphologies with fan-shaped leading lamellae while the following cells had cell contacts on all sides and appeared to lack leading lamellae. In the present ultrastructural study, the following cells frequently showed tapering cytoplasmic protrusions and leading lamella-like processes underlapping a preceding cell, indicating that the locomotion mechanism is almost the same for both the leading and following cells. For this type of locomotion as a coherent sheet we propose that localized modulation of cell-cell adhesion was induced such that wide intercellular gaps occurred at the lower portion of the cells to allow the cells to extend the tapering cytoplasmic processes and leading lamellae while close cell-cell contacts remained at the upper portion of the cells. These TPA-induced changes took place predominantly in the cells at the periphery of the cell islands, while the cells in the middle of the cell islands maintained close cell-cell contacts including complex interdigitation all around the cells, suggesting the modulation of TPA action by cell-cell interaction. Additionally, consistent with the evidence for junctional complexes between the cells moving outwards, the Lucifer-yellow dye transfer studies showed some, limited cell-cell coupling, suggesting the presence of at least some gap junctional intercellular communication in the moving cell sheets.     

Joint-specific disruption of control during arm movements in Parkinson’s disease

The leading joint hypothesis (LJH) suggests distinct types of control (leading and subordinate) at different joints during multi-joint movements. Taking into account specific features of movements in Parkinson’s disease (PD), the LJH predicts distinct effect of PD on control of leading and subordinate joints: impaired interaction torque (INT) regulation should be emphasized at the subordinate joints, and impaired generation of muscle torque (MUS) magnitude should be more pronounced at the leading joint. This prediction was tested by studying three tasks of horizontal shoulder-elbow movements in PD patients and age-matched controls: cyclic line drawing, cyclic point-to-point, and discrete pointing movements. Each task included movements in different directions, providing both shoulder-lead and elbow-lead control patterns. Torque analysis supported the prediction, specifically for Tasks 2 and 3 in which movement targets were chosen to emphasize the shoulder- and elbow-lead control patterns. Patients did not exploit INT for motion generation as successfully as controls did, but only at the subordinate joint. Underproduction of MUS by PD patients was more apparent at the leading than subordinate joint. The results support joint-specific effect of PD on movement control. They also suggest that dyscoordination of joint motions in PD stems predominantly from impaired control of subordinate joints, while bradykinesia is associated more with control of the leading than subordinate joint. Possible contribution of the revealed impairments in joint control to some other movement features in PD is discussed. The study demonstrates the efficiency of the LJH application for revealing changes in joint control caused by motor disorders.     

Mechanism of the oxidative coupling of phenols: Influence of pH upon the electrochemical oxidation of xylenol in methanol

In acidic methanol, xylenol undergoes a bielectronic one step oxidation leading to the phenoxonium cation. Above pH 5,2 the reaction takes place in two monoelectronic steps, the first of which leading to a free radical. C? C coupling, leading to quinones, occurs with the cation, whereas the free monomeric radical undergoes polymerization by C? O coupling. The influence of the pyridine concentration upon the orientation of the coupling may be explained by the coincidence between the pK_A of pyridine in methanol and the pH which favours disproportionation of the monomer radical.     

Etiology of alcoholism: relevance of prenatal hormonal influences on the brain, anomalous dominance, and neurochemical and pharmacological brain asymmetry

Because of possible prenatal hormonal influences on the brain, leading to anomalous dominance, pharmacological and neurochemical asymmetry, and consequent antisocial personality and phobic anxiety, the subject ingests ethanol for its tension-reducing properties via endorphinergic activation and the dopaminergic reward system. Due to presence of stress, and effects of anomalous dominance on ethanol metabolizing enzymes, ethanol-oxidizing systems are activated leading to high rates of ethanol elimination from the blood, and thus the decreased intensity of reaction to ethanol, leading to tolerance. Since stress can cause a decrease in the number of opiate receptors, a vicious cycle of ingesting more and more ethanol may be instituted.     

Epithelial migration in organ culture. A morphological and time lapse cinematographic analysis of migrating stratified squamous epithelium.

The migration of stratified squamous epithelium in organ cultures of rat palatal explants has been studied using scanning and transmission electron microscopy. The scanning microscope revealed plate-like folds at the margins, and microvilli on the bodies of cells. These structures were most highly developed on those cells nearest the leading edge of the sheet of cells and are interpreted as an index of cells that are migrating. The cells at the leading edge have broad flat pseudopodia in direct contact with the collagen bundles. A time lapse cinemicrographic study showed that the net forward movement of cells (nuclei) remote from the leading edge was at least as great as that at the leading edge immediately in front of them and the distance they travelled was greater than that of the leading edge. In transmission electron micrographs of these migrating epithelial cells from in vivo wounds, profiles that could correspond to the microvilli and plate-like folds could be found on the surface of the migrating cells. The results of this study suggest a simple model for the particular type of movement that occurs in stratified squamous epithelium in healing wounds where a mass of cells is produced that can both migrate into the wound and undergo stratification and cornification. A tracked vehicle shedding a broken track is used as an analogy of the model proposed.     

Leading causes of death in England and Wales--how should we group causes?

This article examines how best to identify the leading causes of mortality in England an Wales, by using different way of grouping causes of death, based on a list developed by the World Health Organization (WHO). Four different versions of this list are compared. The leading cause of death across all age groups depends on the ways in which common diseases and external causes are aggregated or disaggregated into groups. Areas of particular debate, examined in this article, are the grouping or splitting of accidents by mechanism and cancers by site within leading cause lists. These affect which causes appear in the top ten, and their order in different age groups.     

Inhibition of clone formation as an assay for T cell-mediated cytotoxicity: short-term kinetics and comparison with 51Cr release.

The short-term kinetics of T cell-mediated cytotoxicity was investigated using a cloning inhibition assay. Murine cytotoxic thymus-derived lymphocytes (CTL) generated in vitro in mixed leukocyte cultures (MLC), were incubated for various periods of time at 37 degrees C with allogeneic mastocytoma target cells. The mixtures were then plated in soft agar, and mastocytoma clone formation was assessed after 5-7 days incubation. Using this technique, it was demonstrated that events leading to the loss of cloning ability could be detected after 1-3 min incubation at 37 degrees C, and after 20-30 min, 95% of the clone forming cells had been inactivated. When these results were compared directly with those obtained using the conventional 51Cr-release assay, it was found that the events leading to loss of cloning ability occurred more rapidly than indicated by the isotope assay. However, a modification of the 51Cr-release assay involving EDTA addition, gave comparable results to the cloning inhibition assay. These results raise the possibility that the events leading to 51Cr-release of tumor target cells may be related in time to those leading to the loss of cloning ability.     

Hypoprothrombinemia Due to Cefamandole

Summary Two patients are described with severe coagulation disturbances, in one instance leading to extensive skin bleeding, secondary to the use of cefamandole. This cefalosporin antibiotic carries the same N-methylthiotetrazole side chain as moxalactam. Pathogenetic mechanisms leading to hypoprothrombinemia, its prevention and treatment are discussed.Abbreviations MTT N-methylthiotetrazole - PIVKA proteins induced by vitamin K absence or antagonists     

Responses of single units in the monkey superior colliculus to moving stimuli

1. Single unit responses of pan-directional cells to moving and stationary flashing stimuli were studied in the superficial layers of the superior colliculus in paralysed, anaesthetized rhesus monkeys. The aim of this study was to see how far cell responses to moving stimuli fit in with what would be expected from their responses to stationary flashing stimuli. 2. Both the leading and the trailing edge of a moving stimulus evoke a transient response. If the diameter of moving light spots is increased the strength of the leading edge response increases, reaches a maximum and decreases to a constant value which is similar to the behaviour of the on response when the diameter of flashing spots is increased. The strength of the trailing edge response increases and reaches the same strength as that of the leading edge response. If the width of a long moving slit is increased, the strength of the leading edge response is the same at all slit widths, while the strength of the trailing edge response shows a course similar to that of the trailing edge response if the spot diameter is increased. If the length of a wide moving slit is increased both the leading and the trailing edge responses decrease. These results indicate that the strength of both leading and trailing edge responses is dependent on the degree the inhibitory surround is activated. 3. The leading and the trailing edge of a stimulus evoke their responses at the same position in the receptive field independent of the direction of movement. 4. Increasing the velocity of a moving stimulus shows that in general the leading edge response is present up to higher velocities than the trailing edge response independent of the sign of contrast. The burst duration to moving stimuli decreases with increasing stimulus velocity and appears to be determined by the time a moving edge is present in the receptive field centre. When this time becomes shorter than 10--20 ms, the burst duration for moving stimuli is constant and about the same as for flashing stimuli. This indicates that, although spatial receptive field properties can vary considerably, temporal receptive field properties show a strong similarity among different units. 5. The response latencies to light and dark moving edges are the same, which in turn are about equal to the response latencies to stationary flashing stimuli. 6. Stimulation experiments show that the general response characteristics to moving stimuli can be predicted by using a set of receptive field parameters derived from responses to stationary flashing stimuli. The most important variable of moving stimuli appears to be the period of time a moving contour is present within the receptive field centre, besides the degree of activation of the inhibitory surround.     

Measurement of chemotaxis of human polymorphonuclear leukocytes in filters by counting the number of cells in a single plane and comparison with leading front method

A method is described for measuring the chemotactic response in filters of human neutrophils by counting the number of cells in a single plane at a constant distance below the top of the filters. This method gives results that are similar to those obtained by counting the total number of cells that have migrated into the filters. The results obtained by this method are compared with the leading front method. Under most conditions the results are similar whether obtained by the leading front or cell number methods except that counting the number of cells is often more sensitive. In the presence of p-nitrophenyl 4-chlorobutylphosphonate, however, the chemotactic response appeared to be inhibited as determined by counting the number of cells stimulated to migrate but enhanced as measured by the leading front method.     

Ultrasound measurement of wall thickness in the carotid artery: fundamental principles and description of a computerized analysing system.

A B-mode [two-dimensional (2D)] image from the carotid artery may be described as containing seven echo zones. The aim of the present work is to discuss how lumen diameter and wall thickness can be measured from these zones, and to review some of the basic principles of ultrasound physics and imaging. Simple experiments were performed to identify the echoes defining intima-lumen interfaces. The results showed that: (1) The intima-media thickness of the near wall cannot be measured in a valid way. (2) The lumen diameter of a blood vessel is defined by the distance from the leading edge of the intima-lumen interface of the near wall (echo zone 3) to the leading edge of the lumen-intima interface of the fall wall (echo zone 5). (3) Previously published studies have validated the intima-media complex of the far wall as the distance from the leading edge of the lumen-intima interface of the far wall to the leading edge of the media-adventitia interface of the far wall (echo zone 7). We suggest that if measurements on the near wall are performed, measurements from the far wall should also be presented separately, and if lumen diameter is measured, that this measurement is carried out according to the leading edge principle. We describe a computerized analysing system for the measurement of wall thickness and plaque area on the carotid and femoral arteries. The system is based on a low-cost PC and a frame grabber board and calculates minimum, maximum and mean values of lumen diameter and wall thickness from a section of the artery.     

青光眼相关生物力学研究进展

原发性青光眼已成为全球第二致盲眼病.其发病原因很多,病程发展的主要力学原因是各种因素引起的眼压升高,致使视觉细胞或视神经受到持续压迫,最终导致视野受损致盲.本文主要就闭角型青光眼相关的生物力学研究现状做一简要综述.     

Controlling horizontal deceleration during gait termination in transfemoral amputees: Measurements and simulations

In this study we investigated how leading limb angles combined with active ankle moments of a sound ankle or passive stiffness of a prosthetic ankle, influence the center of mass (CoM) velocity during the single limb support phase in gait termination. Also, we studied how the trailing limb velocity influences the CoM velocity during this phase. We analyzed force plate data from a group of experienced transfermoral (TF) amputee subjects using a prosthetic limb, and the outcome from a two-dimensional mathematical forward dynamics model. We found that when leading with the sound limb, the subjects came almost to a full stop in the single limb support phase, without the use of the prosthetic limb. When leading with the prosthetic limb, the CoM deceleration was less in a relatively short single limb support phase, with a fast forward swing of the trailing sound limb. Slowing down the heavier trailing sound limb, compared to the prosthetic limb, results in a relatively larger braking force at the end of the swing phase. The simulations showed that only narrow ranges of leading limb angle and ankle moments could be used to achieve the same CoM velocities with the mathematical model as the average start and end velocities of the prosthetic limb user. We conclude that users of prosthetic limbs have a narrow range of options for the dynamics variables to achieve a target CoM velocity. The lack of active control in the passive prosthetic ankle prevents the TF amputee subjects from producing sufficient braking force when terminating gait with the prosthetic limb leading, forcing the subjects to use both limbs as a functional unit, in which the sound limb is mostly responsible for the gait termination.