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Growing evidence has shown that the p75 neurotrophin receptor (p75NTR) may play important roles in controlling neuronal survival or cell apoptosis within the central nervous system in development, and in pathological or neural injury. Recent studies have further revealed that p75NTR acts as a “molecular signal switch” that determines cell death or survival by three processes. First, pro-nerve growth factor (proNGF) triggers cell apoptosis by its high affinity binding to p75NTR, while NGF induces neuronal survival with lowaffinity binding. Second, p75NTR mediates cell death by combining with co-receptor sortilin, whereas it promotes neuronal survival through combination with proNGF. Third, release of the intracellular domain chopper or cleavaged “short p75NTR” can independently initiate neuronal apoptosis. We have identified the cell self-destructive proNGF-p75NTR-sortilin signalling apparatus assembled in ventral tier dopamine neurons of the substantia nigra pars compacta, suggesting that p75NTR signalling might be involved in selective cell death mechanisms of substantia nigra neurons or disease progression of Parkinson's disease (PD). In addition, experimental manipulation of p75NTR benefited cell survival of cholinergic or motor neurons and improved disease progression of the neurodegenerative diseases Alzheimer's disease and Amyotrophic lateral sclerosis. The proNGF-p75NTR-sortilin signalling complex may thus provide new target for neuroprotection of substantia nigra neurons and the therapeutic treatment of PD.

Multiple drilling is reported to be an effective treatment for osteonecrosis of the head of femur, but its effect on intra-osseous pressure has not been described. We undertook multiple drilling and recorded the intra-osseous pressure in 75 osteonecrotic hips in 60 patients with a mean age of 42 years (19 to 67). At a mean follow-up of 37.1 months (24 to 60), 42 hips (56%) had a clinically successful outcome. The procedure was effective in reducing the mean intra-osseous pressure from 57 mmHg (SD 22) to 16 mmHg (SD 9). Hips with a successful outcome had a mean pressure of 26 mmHg (SD 19). It was less effective in preventing progression of osteonecrosis in hips with considerable involvement and in those with a high intra-osseous pressure in the intertrochanteric region (mean 45 mmHg (SD 25)). This study is not able to answer whether a return of the intra-osseous pressure to normal levels is required for satisfactory healing.

Parkinson' disease (PD) is a most common and debilitating degenerative disease resulted from massive loss of dopamine neurons in the substantia nigra pars compacta, which is characterized by severe motor symptoms of tremor, bradykinesia, rigidity and postural instability. Protection of nigral dopamine neurons from progressive degenerative death and cell replacement of novel dopamine neurons are hopeful strategies against PD in humans. The reactive astrocytes or functional activation of astrocytes abundantly occurred in brain insults including trauma, ischemia, and 6-OHDA or MPTP-treated PD animal models. Although they were traditionally assumed to impede neuronal regeneration by forming glial scars, growing evidence has indicated that reactive astrocytes do offer crucial benefits in functional recovery of brain injuries. The reactive astrocytes can produce various neurotrophic factors for neuron survival, synthesize extracellular substrates for axonal outgrowth and synaptogenesis, act as scavengers for free radical and excess glutamate, and promote neurogenesis of neural progenitor cells in the adult brains. We thereafter hypothesize that reactive astrocytes may also play important roles in the protection of nigral dopamine neurons or transplanted dopamine cells through their neurotrophic functions and active interaction with dopamine neurons or neural progenitor cells. Future approaches deserve to target on neurotrophic functions of reactive astrocytes in the basal ganglia and interventions to facilitate survival and axonal regeneration of dopamine neurons or differentiation of dopamine progenitor cells. Novel pharmaceutical and cell replacement strategies will hopefully be developed by potential manipulation of reactive astrocytes in the basal ganglia in prevention and treatment of Parkinson's disease.

Parkinson's disease (PD) is a serious motor disorder and it is the second most common brain degenerative disease in human. PD is known to be caused by degeneration of dopamine neurons in the substantia nigra but the cause of cell death is largely unknown. Mammalian neurokinins [NKs] are a group of neuropeptides that include substance P (SP; neurokinin-1, NK-1), substance K (SK; NK-2; neurokinin A), and neuromedin K (NK; NK-3; neurokinin B). Their biological effects as neurotransmitters, neuromodulators, or neurotrophic-like factors are mediated by three distinct neurokinin receptors, namely SP receptor (SPR: NK-1 receptor, NK-1R), SKR (NK-2R), and NKR (NK-3R). Several lines of evidence have indicated that neurokinins are implicated in the pathogenesis of PD. First, decreases of SP level and SP-immunoreactivity have been found in nigral and striatal tissues of animals with PD and postmortem PD patients. Second, NKs exert neuroprotective effects on neurons. In addition, NK receptors, namely NK-1 and NK-3 receptors, are abundantly localized in dopaminergic and cholinergic neurons of the basal ganglia, indicating that these neurons are under the physiological regulation of NKs. Moreover, modulation in motor activity occurred in 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-treated mice, PD animal model, after systemic administration of NK receptor agonists. NKs and NK receptors, therefore, might be important molecules that are associated with functions and survival of neurons in the basal ganglia, in particular the dopamine neurons. Further studies should be devoted to elucidate the functional roles of NK systems in (a) the neuropathogenesis and neuroprotection during the course of PD, (b) the efficacy of NK receptor drugs towards PD, and (c) potential therapeutic intervention that targets at the prevention or treatment of PD.

The distribution of high-affinity neurotrophin receptors in cells of the vestibular nuclear complex and its subnuclei of adult rats was examined. We noted a high density of tyrosine kinase (Trk) A- and B- and a lower density of TrkC-immunostained cells. In particular, long, intensely labelled immunostained-TrkB fibres formed networks in the neuropil. Both TrkA- and TrkB-immunostained cells were widely distributed in the lateral, medial and spinal vestibular nuclei, and were less frequently seen in the superior vestibular nucleus, x and y subnuclei. However, immunostaining for TrkC was weak in many cells within the vestibular nuclei. The widespread and abundant neuronal distribution of Trk receptors predicts that their associated neurotrophins exert significant effects on individual cells within the vestibular nuclei.

The response properties of extracellularly recorded Y group neurons on the lesioned side were examined in decerebrate cats after acute hemilabyrinthectomy, with the use of constant velocity off-vertical axis rotations (OVAR) to stimulate the remaining intact otolith receptors. During rotation in the clockwise or counterclockwise direction, Y group neurons displayed a spectrum of position-dependent bidirectional response sensitivities, ranging from one- to two-dimensional. Some two-dimensional neurons even exhibited unidirectional responses with change in OVAR velocity. These findings indicate that Y group neurons have the capacity to code spatiotemporal signals arising from the contralateral otolith. The best response orientations of one-dimensional and two-dimensional neurons were found predominantly along the antero-posterior direction, thus providing a spatial framework for the otolithic reflexes.

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With the use of floating electrodes we recorded from the C2 dorsal root ganglion of decerebrate cats during sinusoidal and trapezoidal head rotation. Fifty-one spontaneously firing afferents were identified as muscle spindle endings. Some were identified by their excitatory response to injection of succinylcholine, others by the similarity of their behavior to that of endings excited by the drug. Because afferent input to the ganglion was restricted by sectioning most nerve trunks, most spindle endings were presumably located in ventral and ventrolateral perivertebral muscles. The firing of each spindle afferent was modulated most effectively by tilting the head in a specific direction; this direction was termed its response vector. Responses to sine waves and trapezoids were then studied with stimuli oriented as closely as possible to the vertical plane of this vector. Most spindle afferents could be classified in one of two categories. Those with high gain, pronounced nonlinearity, and high dynamic index were called type A. Those classified as type B had low gain, a fairly linear response, and low dynamic index. In response to small (0.5 degrees) stimuli, type A endings had phase leads of approximately 40 degrees at frequencies of sinusoidal stimulation of 0.02-0.1 Hz, increasing to approximately 80 degrees at 4 Hz; with larger (2.5 degrees) stimuli, phase was advanced by an additional 10-20 degrees at all frequencies. Phase of type B responses was less advanced than that of type A responses. Gain slopes of the two types of endings were similar. Bode plots of spindle afferents strongly resembled those of upper cervical neurons whose activity is modulated by head rotation. Each spindle afferent had a response vector whose direction remained stable with time, different frequencies of stimulation, and different stimulus amplitudes. The distribution of response vectors covered approximately 270 degrees, with a gap near nose down pitch. Changing initial head position usually had little effect on the direction of an afferent's response vector or on response dynamics. However, stimulation far from the best plane could transform a type A into a type B response. This raises the possibility that type B receptors could be type A receptors best stimulated by yaw and with only low sensitivity to stimulation in vertical planes. Type A receptors have all the properties of spindle primaries. The identification of type B receptors remains uncertain, because they may include secondary afferents as well as primaries stimulated far from their best three-dimensional vector.(ABSTRACT TRUNCATED AT 400 WORDS)

In ketamine anesthetized cats, the contralateral labyrinth, the ipsilateral utricle, the ipsilateral horizontal and anterior semicircular canal nerves were completely destroyed, leaving the ipsilateral saccule intact. Neurons in the Deiters' nucleus, driven by electrical stimulation of the superior saccule, were responsive to static tilts in the antero-posterior direction. Results suggest that the saccule is capable of conveying information on head positional changes in the antero-posterior direction and that such information is retained at the level of the Deiters' nucleus.

A missense mutation (A385 to T), predicting an Ile129 to Phe substitution, in the human Secretor alpha 1,2-fucosyltransferase gene was present in double dose in Lewis(a+b+) individuals, but not in Lewis(a-b+) individuals. Co-segregation of the Lewis(a+b+) phenotype with homozygosity for the mutation was also verified. These results yield a potential molecular basis for the weak Secretor allele (Sew) accounting for the Lewis(a+b+) phenotype.

Experimental evidence indicates that the autonomic nervous system, especially the cholinergic pathway, modulates the mucosal defensive mechanism and affects mucosal damage in the stomach. The present study investigated the role of the dorsal motor nucleus of vagus (DMV) in gastric function and its influences on ethanol-induced mucosal damage in pentobarbitone-anesthetized rats. Electrolytic lesion of the DMV as compared with sham operation and lesions of other brain areas, eg, nucleus reticular gigantocellularis and cuneate nucleus, reduced the basal gastric mucosal blood flow (GMBF) and also the blood flow after ethanol administration. The same operation did not affect the acid secretion either in the basal state or during the ethanol treatment period. Lesions at the caudal half of the DMV produced a bigger depression of GMBF when compared with lesion at the rostral half. In the sham-operated rats, ethanol induced severe hemorrhagic lesions in the gastric glandular mucosa, and this was significantly potentiated by lesions at the DMV, especially in the caudal half. The present findings indicate that acute DMV damage at the caudal half markedly affects the GMBF but not the acid secretion. The action on GMBF may contribute to the aggravation of ethanol-induced gastric damage in rats. These data reinforce the idea that the central vagal pathway, especially the caudal half of the DMV, plays a significant role in the modulation of GMBF, which in turn affects the integrity of gastric mucosal barrier.

In cats which were decerebrated and unilaterally labyrinthectomized on the day of the experiment, the responses of neurons in the y group nucleus on the lesioned side were studied during constant velocity off-vertical axis rotations, which selectively stimulated the remaining intact otolith receptors. During 360° rotations, neurons exhibited position-dependent modulation in discharge rate, thus showing that the y group neurons receive signals of head positional changes from the contralateral otoliths. Most y group neurons had their best response orientations within ±45° of the head-up and head-down positions (i.e. antero-posterior or pitch direction) in the plane of rotation studied. This implies that the spatial coding property of these otolith neurons enables them to be particularly catered for small head tilts about the sagittal plane of the animal.

Abstract:  In decerebrate cats that had been acutely hemilabyrinthectomized (HL), the extracellular activities of vestibular nuclear neurons on the lesioned and labyrinth-intact sides were studied during constant-velocity off-vertical axis rotations (OVAR) in the clockwise (CW) and counterclockwise (CCW) directions (at 10° tilt). Over the range of 1.75–15°/s, two types of neuronal responses were identified on both sides. Some neurons showed symmetric and velocity-stable bidirectional response sensitivity (δ defined as the CW gain over the CCW gain) while other neurons exhibited asymmetric and velocity-variable δ. The mathematically derived gain tuning ratios of these two groups of neurons were within the range of one-dimensional and two-dimensional neurons respectively. The best response orientations in one-dimensional neurons and the orientations of the maximum response vector, S max, in two-dimensional neurons were found to point in all directions on the horizontal plane. On the labyrinth-intact side, both the one-dimensional and two-dimensional neurons showed asymmetry in the neuron numbers and/or the response gains between the two roll quadrants as well as between the two pitch quadrants. In addition, both the neuron number and gain were significantly higher for neurons in the head-down/ipsilateral-side-down half-circle than those in the head-up/contralateral-side-down half-circle. None of the aforementioned asymmetries was observed on the lesioned side. That a comparable pattern of distribution was observed in the one-dimensional and two-dimensional neurons suggests that these neurons maintain a common spatial reference frame in encoding head orientational signals arising from the ipsilateral and contralateral otoliths. Furthermore, a predominance of two-dimensional neurons that exhibited a greater gain with CW rotations was observed on both sides of HL cats. Of the response dynamics observed amongst neurons on the two sides of HL cats, no difference was found with regard to the response gain and the pattern of response lead. However, a difference in response lag was observed between neurons on the two sides of HL cats. These suggest that there is a segregation of otolithic signals to reach the ipsilateral and contralateral vestibular nuclei. Taken together, the present study demonstrates that one-dimensional and two-dimensional neuronal responses could be elicited with inputs arising solely from the ipsilateral or contralateral otoliths. The observed orientational tuning and the CW-CCW asymmetry to bidirectional rotation may provide the essential directional coding of head orientations. Further, the imbalance of spatial/dynamic response patterns between the bilateral vestibular nuclei following the restriction of otolith inputs by HL implies that converging otolithic inputs from the bilateral labyrinths are essential for producing the neuronal responses in control animals. The results are also discussed in terms of the possible contribution of the various neural asymmetries between neuronal subpopulations in the bilateral vestibular nuclei to the behavioral symptoms accompanying acute HL.

Coliphage content of sewage collected from 11 different localities in Hong Kong was determined. The number of plaque-forming units (PFU) ranged from 0.036 × 103to 15.9 × 103per ml. In general, urban sewage tended to be richer than rural sewage both in PFU count as well as plaque morphological variation. Seventy-seven isolates were subjected to a host range study. Fifty per cent of these were able to grow on Escherichia coliK-12 as well as E. coliB. Approximately 32% were found to be male specific, and the remaining 18% were K-12 specific although sex-indifferent.

To investigate whether neurons in the medullary reticular formation of decerebrate cats can encode spatial orientation during 360° off-vertical axis rotations (OVAR), responses of these units were studied during constant velocity OVAR in clockwise (CW) and counterclockwise (CCW) directions. Tilt-sensitive units, some of which were activated by antidromic stimulation of the thoracic cord, were found to respond to 360° OVAR with position-and direction-dependent modulation in discharge rates. For the individual responsive unit there was a difference in the spatial location of the CW and CCW discharge maxima, while a comparable response gain was obtained for rotations in either direction. The orientation of the best response of each unit was not significantly modified by changes in the amplitude of head tilt and/or velocity of rotation. Such characterized directional axes of the medullary reticular units were found to have a fairly equal distribution over the 360°. The role that neurons in the medullary reticular formation plays in encoding otolith inputs with respect to head movements is discussed.

A numerical model of the microwave heating of distilled water is developed using COMSOL Multiphysics software to investigate the microwave effects on the heating rate. Three frequencies (0.915GHz, 2GHz and 2.45 GHz) have been applied in the model in order to study their influences on the water temperature. It is found that the water heats up at 2GHz and 2.45GHz, however, there is no sign of heating at 915MHz. This is supported with the figures of the electric field distribution in the microwave cavity. The results shown in the developed model is validated with the experimental results obtained at 2.45 GHz.

In this study, particle size distribution and zeta potential of the suspended particles in municipal water and lake surface water of Curtin Sarawak's lake were compared and the samples were analysed using dynamic light scattering method. High concentration of suspended particles affects the water quality as well as suppresses the aquatic photosynthetic systems. A new approach has been carried out in the current work to determine the particle size distribution and zeta potential of the suspended particles present in the water samples. The results for the lake samples showed that the particle size ranges from 180nm to 1345nm and the zeta potential values ranges from -8.58 mV to -26.1 mV. High zeta potential value was observed in the surface water samples of Curtin Sarawak's lake compared to the municipal water. The zeta potential values represent that the suspended particles are stable and chances of agglomeration is lower in lake water samples. Moreover, the effects of physico-chemical parameters on zeta potential of the water samples were also discussed.

Magnesium peroxide is an excellent source of oxygen in agriculture applications, for instance it is used in waste management as a material for soil bioremediation to remove contaminants from polluted underground water, biological wastes treatment to break down hydrocarbon, etc. In the present study, sol-gel synthesis of magnesium peroxide (MgO2) nanoparticles is reported. Magnesium peroxide is odourless; fine peroxide which releases oxygen when reacts with water. During the sol-gel synthesis, the magnesium malonate intermediate is formed which was then calcinated to obtain MgO2 nanoparticles. The synthesized nanoparticles were characterized using Thermo gravimetric -Differential Thermal Analysis (TG- DTA), X-Ray Diffraction studies (XRD) and High Resolution Transmission Electron Microscope (HRTEM). Our study provides a clear insight that the formation of magnesium malonate during the synthesis was due to the reaction between magnesium acetate, oxalic acid and ethanol. In our study, we can conclude that the calcination temperature has a strong influence on particle size, morphology, monodispersity and the chemistry of the particles.

A simple, low cost interspike interval analyzer for the analysis of trains of nerve impulses is described. The analyzer is built with readily available integrated circuits and has been used to analyze spike trains in the lateral vestibular nucleus of cats.

2 populations of cells were found in the Deiters' nucleus responsive to direct electrical stimulation of the ipsilateral saccule. Only those Deiters' neurons activated monosynaptically from the saccule could be driven antidromically from the oculomotor nucleus. Such an intracellular study provides strong evidence for a tri-neuronal arc in the sacculo-ocular reflex for vertical eye movements.

Article abstract-We studied the apolipoprotein E (apoE) allele frequencies in 65 Chinese patients with late-onset Alzheimer's disease (AD) and 82 age- and sex-matched controls. The apoE epsilon 4 allele frequency was significantly higher in the AD group than in the control group (0.169 versus 0.067, p < 0.01). There were five homozygotes for epsilon 4 in the AD group but none among the controls. The odds ratio for AD was 1.6 for epsilon 4 heterozygotes. The age at onset was lower with the presence of the epsilon 4 allele and higher with the epsilon 2 allele, although neither of these differences reached statistical significance.