The role of GABA(A) and GABA(B) receptors in the control of GnRH release in anestrous ewes

The paper reviews data concerning the involvement of GABA(A) and GABA(B) receptors in the control of GnRH secretion in anestrous ewes. Generally, GABA influences the GnRH release through GABA(A) and GABA(B) receptors located on perikaria of the GnRH neurons in the preoptic area (MPOA) or through the influence on beta-endorphinergic and catecholaminergic systems activity in MPOA and in ventromedial-infundibular region of the hypothalamus (VEN/NI). Stimulation of GABA(A) receptors in VEN/NI and MPOA attenuates GnRH release, while activation of GABA(B) receptors in MPOA decreases GnRH secretion, and in VEN/NI increases concentration of GnRH. The different neural mechanisms could be involved in this process: direct ligand action on the GABA(A) and GABA(B) receptors located on GnRH cells and axon terminals or indirect effect through the changes in the beta-endorphinergic and catecholaminergic systems activity in these structures of the brain.     

Motion control of the ankle joint with a multiple contact nerve cuff electrode: a simulation study

The flat interface nerve electrode (FINE) has demonstrated significant capability for fascicular and subfascicular stimulation selectivity. However, due to the inherent complexity of the neuromuscular skeletal systems and nerve–electrode interface, a trajectory tracking motion control algorithm of musculoskeletal systems for functional electrical stimulation using a multiple contact nerve cuff electrode such as FINE has not yet been developed. In our previous study, a control system was developed for multiple-input multiple-output (MIMO) musculoskeletal systems with little prior knowledge of the system. In this study, more realistic computational ankle/subtalar joint model including a finite element model of the sciatic nerve was developed. The control system was tested to control the motion of ankle/subtalar joint angles by modulating the pulse amplitude of each contact of a FINE placed on the sciatic nerve. The simulation results showed that the control strategy based on the separation of steady state and dynamic properties of the system resulted in small output tracking errors for different reference trajectories such as sinusoidal and filtered random signals. The proposed control method also demonstrated robustness against external disturbances and system parameter variations such as muscle fatigue. These simulation results under various circumstances indicate that it is possible to take advantage of multiple contact nerve electrodes with spatial selectivity for the control of limb motion by peripheral nerve stimulation even with limited individual muscle selectivity. This technology could be useful to restore neural function in patients with paralysis.     

An optical brain-to-brain interface supports rapid information transmission for precise locomotion control

Brain-to-brain interfaces(BtBIs) hold exciting potentials for direct communication between individual brains. However,technical challenges often limit their performance in rapid information transfer. Here, we demonstrate an optical brain-to-brain interface that transmits information regarding locomotor speed from one mouse to another and allows precise, real-time control of locomotion across animals with high information transfer rate. We found that the activity of the genetically identified neuromedin B(NMB) neurons within the nucleus incertus(NI) precisely predicts and critically controls locomotor speed. By optically recording Ca~(2+) signals from the NI of a "Master" mouse and converting them to patterned optogenetic stimulations of the NI of an "Avatar" mouse, the Bt BI directed the Avatar mice to closely mimic the locomotion of their Masters with information transfer rate about two orders of magnitude higher than previous Bt BIs. These results thus provide proof-of-concept that optical Bt BIs can rapidly transmit neural information and control dynamic behaviors across individuals.     

Frequency of nosocomial infections as revealed by a prevalence survey

In 1984, a prevalence survey based on the methodology, definitions and criteria meeting the WHO requirements was carried out in the Czech Socialist Republic. This prevalence study on a total of 12,260 hospital patients revealed 751 active cases of nosocomial infection (NI). The conclusions emerging from an epidemiological analysis of the collected NI patient records were as follows: 60% of all infections were acquired on the surgical services, predominantly on the surgery service; 60% of those who developed NI were persons over 50 years of age; hospital-associated infections afflicted 366 males and 385 females; the ratio of infections acquired prior to hospital presentation to those originating while in hospital care was about 4:1, with a tendency to vary depending on type of hospital service; the urinary tract was the most frequent site of infection (25%), followed by surgical wounds (15%) and upper respiratory tract (13%); 17% of NI patients contracted the infection in spite of preventive doses of antimicrobials, 28% of NI patients received no antimicrobial prophylaxis; among the 78% (589 out of 751) of patients examined bacteriologically, 46% of infections were caused by Gram-negative rods, 19% by staphylococci, 7% by streptococci and 6% by Pseudomonas aeruginosa; 22% of NI patients were not examined for the pathogen. The prevalence survey methodology turned out to be useful as a tool for detecting the immediate magnitude of the NI problem, but can also be used as a control method.     

Poliomyelitis and parenteral injections; a review of recent literature

Data presented in the literature as to the relationship of poliomyelitis and recent prior injections include several aspects. the coincidence of paralysis in the same site as a recent injection has been considered the most definitive evidence. The fact of an inordinately large number of cases of paralysis of an arm where a recent previous antigen injection was recorded offered less specific corroboration. The larger number of cases among persons who had had an injection in the month preceding onset than among persons with injections in more distant months was noted. This observation was supported when similar information was obtained in a comparison of injection histories for persons who had the disease with the histories of persons who did not have it. The interval between injection and onset among persons who had the disease within a month of injection suggested something other than chance relationship. There is limited information indicating increased severity of paralysis in the injected limb. Evidence is divided on whether or not there is more paralytic disease among patients with recent injections. Similarly, the evidence is no more than suggestive with regard to increased severity of spinal paralytic disease. The mechanism or nature of such a phenomenon is unexplained. However, as Anderson and Skaar said, "considerable attention must be attached to the fact of uniformity of results in a series of independent observations even though each may be small."     

Global rhythmic activities in hippocampal neural fields and neural coding

Global oscillations of the neural field represent some of the most interesting expressions of the hippocampal activity, being related also to learning and memory. To study oscillatory activities of the CA3 field in theta range, a model of this sub-field of Hippocampus has been formulated. The model describes the firing activity of CA3 neuronal populations within the frame of a kinetic theory of neural systems and it has been used for computer simulations. The results show that the propagation of activities induced in the neural field by hippocampal afferents occurs only in narrow time windows confined by inhibitory barrages, whose time-course follows the theta rhythm. Moreover, during each period of a theta wave, the entire CA3 field bears a firing activity with peculiar space-time patterns, a sort of specific imprint, which can induce effects with similar patterns on brain regions driven by the hippocampal formation. The simulation has also demonstrated the ability of medial septum to influence the global activity of the CA3 pyramidal population through the control of the population of inhibitory interneurons. At last, the possible involvement of global population oscillations in neural coding has been discussed.     

Spinal cord injury. Rehabilitation adds life to years.

The National Spinal Cord Injury Statistical Center data base contains information collected prospectively on 13,763 persons injured since 1973 and treated at model systems of care throughout the United States. These data clearly demonstrate improved neurologic status and independent function in activities of daily living following acute care and rehabilitation for most persons with spinal cord injuries. Decreased lengths of initial and subsequent hospital stays and increased survival rates are also documented. Most persons are discharged to a private residence in the community and remain there. Many complete their educations and return to gainful employment after injury. Spinal cord injury has only a short-term effect on marriage and divorce rates, which appears to dissipate within a few years after injury. Overall, these figures demonstrate the dramatic improvements in length and quality of life achieved by most persons with spinal cord injuries during the past two decades.     

Influence of the compensation of the geomagnetic field on human cognitive processes

The influence of the compensation of the geomagnetic field to a level less than 0.4 microT on human cognitive processes has been studied. Forty persons took part in the study; they were divided by sex and age into four groups. The cognitive abilities of the persons were tested. Each person took part in two experiments: in control conditions and under the exposure to zero magnetic field. A 45-min exposure to zero magnetic field caused statistically significant changes in five of eight parameters of the cognitive tests. The magnitude of the effects varied between 1.3 and 6.2%, with an average value for all tests being 2.1% (p < 0.002, MANOVA). Exposure to zero magnetic field led predominantly to an increase in the number of errors and the time the task was performed as compared with the controls. Men passed the tests in zero magnetic field better than women, and young people did it better than aged persons. Groups of persons were distinguished that responded differently to zero magnetic field, the differences being not related to the age or gender.     

Effect of nitric oxide in the nucleus isthmi on the hypoxic and hypercarbic drive to breathing of toads

Nucleus isthmi (NI) is a mesencephalic structure of the amphibian brain that has been reported to participate in CO(2) chemoreception and in the ventilatory response to hypoxia. However, no information exists about the modulators and/or mediators involved. In the present study, we assessed the participation of nitric oxide (NO) in the hypoxic and hypercarbic drive to breathing, specifically in the NI. We compared the ventilatory and cardiovascular responses with hypoxia and hypercarbia after microinjecting 100 nmol/0.5 microliter of N(G)-nitro-L-arginine methyl ester (L-NAME; an NO synthase blocker) into the NI of toads (Bufo paracnemis). L-NAME had no effect under resting conditions. Hypoxia elicited an increase in ventilation in control and vehicle toads by elevating tidal volume (V(T)). Hypercarbia caused hyperventilation in all groups due to an increase in both V(T) and frequency. The microinjection of L-NAME into the NI elicited an increase in ventilatory response to hypoxia and hypercarbia due to a higher V(T.) We conclude that NO in the NI has an inhibitory effect when the respiratory drive is high, acting on V(T).     

Dopaminergic‐like cells from epigenetically reprogrammed mesenchymal stem cells

A number of recent studies have examined the ability of stem cells derived from different sources to differentiate into dopamine‐producing cells and ameliorate behavioural deficits in Parkinsonian models. Recently, using the approach of cell reprogramming by small cell‐permeable biological active compounds that involved in the regulation of chromatin structure and function, and interfere with specific cell signalling pathways that promote neural differentiation we have been able to generate neural‐like cells from human bone marrow (BM)‐derived MSCs (hMSCs). Neurally induced hMSCs (NI‐hMSCs) exhibited several neural properties and exerted beneficial therapeutic effect on tissue preservation and locomotor recovery in spinal cord injured rats. In this study, we aimed to determine whether hMSCs neuralized by this approach can generate dopaminergic (DA) neurons. Immunocytochemisty studies showed that approximately 50–60% of NI‐hMSCs expressed early and late dopaminergic marker such as Nurr‐1 and TH that was confirmed by Western blot. ELISA studies showed that NI‐hMSCs also secreted neurotrophins and dopamine. Hypoxia preconditioning prior to neural induction increased hMSCs proliferation, viability, expression TH and the secretion level of dopamine induced by ATP. Taken together, these studies demonstrated that hMSCs neurally modified by this original approach can be differentiated towards DA‐like neurons.     

Asymmetry in neural fields: a spatiotemporal encoding mechanism

Neural field models have been successfully applied to model diverse brain mechanisms like visual attention, motor control, and memory. Most theoretical and modeling works have focused on the study of the dynamics of such systems under variations in neural connectivity, mainly symmetric connectivity among neurons. However, less attention has been given to the emerging properties of neuron populations when neural connectivity is asymmetric, although asymmetric activity propagation has been observed in cortical tissue. Here we explore the dynamics of neural fields with asymmetric connectivity and show, in the case of front propagation, that it can bias the population to follow a certain trajectory with higher activation. We find that asymmetry relates linearly to the input speed when the input is spatially localized, and this relation holds for different kernels and input shapes. To illustrate the behavior of asymmetric connectivity, we present an application: standard video sequences of human motion were encoded using the asymmetric neural field and compared to computer vision techniques. Overall, our results indicate that asymmetric neural fields are a competitive approach for spatiotemporal encoding with two main advantages: online classification and distributed operation.     

Effect of long term exposure to 0.5 T static magnetic fields on growth and size of GH3 cells

Brief exposure to moderate intensity static magnetic fields has been shown to produce a transient alteration in physiological function in a variety of biological systems, primarily those related to changes in intracellular Ca(2+). In the present study GH3 cells were cultured during continuous exposure to a 0.5 T field, for periods of up to 5 weeks. Following a 1-week exposure, cell growth declined by 22% and returned to control levels in 1 week. This was not statistically significant but, with a 4-week exposure, a statistically significant decline in growth of 51% was observed and return to control levels did not occur for 4 weeks. Cell diameter, on the other hand, significantly increased following 3 weeks of exposure and did not return to control levels for 3 weeks after termination of exposure. Ca(2+)-dependent changes in the dynamic reorganization of the actin cytoskeleton are suggested as the probable explanation for these observations.     

Progress in applying the Three Rs to the potency testing of Botulinum toxin type A

Botulinum toxin type A (BTA) is being increasingly used for a range of therapeutic purposes and also for cosmetic reasons. For many years, the potency of BTA has been measured by using an LD50 assay in mice. This assay is a cause for concern due to its unpleasant nature and extreme severity, and the requirement for high numbers of mice to be used. Alternatives to this potency assay are presently reviewed with particular reference to the work at the National Institute for Biological Standards and Control (NIBSC), and to recent work by the UK manufacturer of the substance. An in vivo local paralysis assay with considerably less severity has been developed and is in use at the NIBSC. Alternative, ex vivo functional assays in use include the measurement of BTA-induced paralysis of neurally-stimulated rodent diaphragm or rat intercostal muscle. The latter method has the advantage of allowing more preparations to be derived from one animal. However, these ex vivo methods have not yet been fully validated and accepted by regulatory agencies as potency assays. Endopeptidase assays, although not measuring muscle paralysis directly, may provide a very useful consistency test for batch release and may replace the routine use of the LD50 test for that purpose. These assays measure the cleavage of the SNAP-25 protein (the final stage of BTA action), and have been validated for batch release by the National Control Laboratory (NIBSC), and are in regular use there. ELISA assays, used alongside the endopeptidase assay, also provide useful confirmatory information on the amounts of functional (and non-functional) BTA present. The UK manufacturer is further validating its endopeptidase assay, an ex vivo muscle assay and an ELISA. It is anticipated that their work will lead to a change in the product license, hopefully within the next two years, and will form a critical milestone towards the end of the LD50 potency test.     

The engram formation and the global oscillations of CA3

The investigation on the conditions which cause global population oscillatory activities in neural fields, originated some years ago with reference to a kinetic theory of neural systems, as been further deepened in this paper. In particular, the genesis of sharp waves and of some rhythmic activities, such as theta and gamma rhythms, of the hippocampal CA3 field, behaviorally important for their links to learning and memory, has been analyzed with more details. To this aim, the modeling-computational framework previously devised for the study of activities in large neural fields, has been enhanced in such a way that a greater number of biological features, extended dendritic trees—in particular, could be taken into account. By using that methodology, a two-dimensional model of the entire CA3 field has been described and its activity, as it results from the several external inputs impinging on it, has been simulated. As a consequence of these investigations, some hypotheses have been elaborated about the possible function of global oscillatory activities of neural populations of Hippocampus in the engram formation.     

A Brain-Machine-Muscle Interface for Restoring Hindlimb Locomotion after Complete Spinal Transection in Rats

A brain-machine interface (BMI) is a neuroprosthetic device that can restore motor function of individuals with paralysis. Although the feasibility of BMI control of upper-limb neuroprostheses has been demonstrated, a BMI for the restoration of lower-limb motor functions has not yet been developed. The objective of this study was to determine if gait-related information can be captured from neural activity recorded from the primary motor cortex of rats, and if this neural information can be used to stimulate paralysed hindlimb muscles after complete spinal cord transection. Neural activity was recorded from the hindlimb area of the primary motor cortex of six female Sprague Dawley rats during treadmill locomotion before and after mid-thoracic transection. Before spinal transection there was a strong association between neural activity and the step cycle. This association decreased after spinal transection. However, the locomotive state (standing vs. walking) could still be successfully decoded from neural recordings made after spinal transection. A novel BMI device was developed that processed this neural information in real-time and used it to control electrical stimulation of paralysed hindlimb muscles. This system was able to elicit hindlimb muscle contractions that mimicked forelimb stepping. We propose this lower-limb BMI as a future neuroprosthesis for human paraplegics.     

RELATION OF A STREPTOCOCCUS TO EPIDEMIC POLIOMYELITIS-Studies in Etiology,Diagnosis and Specific Treatment

The production in 1915 of herpes zoster or "posterior" poliomyelitis in animals with a streptococcus led to further research on the etiologic importance of streptococci in "anterior" poliomyelitis.A specific streptococcus was demonstrated consistently in persons with poliomyelitis and in well persons having contact with them or merely inhabiting an area in which poliomyelitis was epidemic. That the organism was not present in areas remote from contact with the disease was likewise demonstrated.The streptococcus has been isolated from filtrates of poliomyelitis virus and from the tissues and exudates which harbor the virus. It appears in the spinal fluid in the preparalytic stage of poliomyelitis and disappears from the spinal fluid during the severe stage of the disease. Antibody and antigen prepared from the streptococcus were used to determine the presence of antigen and antibody indicative of streptococcal infection in many patients with poliomyelitis and in well persons. The intensity of reaction indicating specific streptococcal antigen was directly proportional to the degree of paralysis in patients; the reaction was greater in persons whose age, sex and previous isolation from the disease would normally indicate greater susceptibility. The test for antibody gave opposite results. Specific agglutinins for the streptococcus and neutralizing antibody for the virus were present consistently in the serum of persons and monkeys during recovery from poliomyelitis. Virus produced in vitro from the associated streptococcus caused all the clinical and pathologic features of poliomyelitis in monkeys inoculated with it, and the animals that recovered from the disease thus induced were proved to be immune thereafter to the natural virus. Antistreptococcic serum prepared in horses was used to treat poliomyelitis. In a group of monkeys inoculated with the virus of the disease, 6 per cent of those receiving the serum before inoculation died of the disease; of the control group, 82 per cent. In a series of poliomyelitis patients treated with the serum the mortality rate was 8 per cent; in a control series, 21 per cent. In a series treated in all stages of the disease by the author, 10 per cent died; of those who did not receive the serum, 25 per cent. An antibody has been prepared from the streptococcus which appears to prevent paralysis and otherwise mitigate poliomyelitis and to provide immunization from the disease.The conclusion is reached that the virus of poliomyelitis is a form of the specific streptococcus, which is the agent in primary infections and in the development of the immunizing antibody.     

RELATION OF A STREPTOCOCCUS TO EPIDEMIC POLIOMYELITIS—Studies in Etiology,Diagnosis and Specific Treatment

The production in 1915 of herpes zoster or “posterior” poliomyelitis in animals with a streptococcus led to further research on the etiologic importance of streptococci in “anterior” poliomyelitis.A specific streptococcus was demonstrated consistently in persons with poliomyelitis and in well persons having contact with them or merely inhabiting an area in which poliomyelitis was epidemic. That the organism was not present in areas remote from contact with the disease was likewise demonstrated.The streptococcus has been isolated from filtrates of poliomyelitis virus and from the tissues and exudates which harbor the virus. It appears in the spinal fluid in the preparalytic stage of poliomyelitis and disappears from the spinal fluid during the severe stage of the disease.Antibody and antigen prepared from the streptococcus were used to determine the presence of antigen and antibody indicative of streptococcal infection in many patients with poliomyelitis and in well persons. The intensity of reaction indicating specific streptococcal antigen was directly proportional to the degree of paralysis in patients; the reaction was greater in persons whose age, sex and previous isolation from the disease would normally indicate greater susceptibility. The test for antibody gave opposite results.Specific agglutinins for the streptococcus and neutralizing antibody for the virus were present consistently in the serum of persons and monkeys during recovery from poliomyelitis.Virus produced in vitro from the associated streptococcus caused all the clinical and pathologic features of poliomyelitis in monkeys inoculated with it, and the animals that recovered from the disease thus induced were proved to be immune thereafter to the natural virus.Antistreptococcic serum prepared in horses was used to treat poliomyelitis. In a group of monkeys inoculated with the virus of the disease, 6 per cent of those receiving the serum before inoculation died of the disease; of the control group, 82 per cent. In a series of poliomyelitis patients treated with the serum the mortality rate was 8 per cent; in a control series, 21 per cent. In a series treated in all stages of the disease by the author, 10 per cent died; of those who did not receive the serum, 25 per cent.An antibody has been prepared from the streptococcus which appears to prevent paralysis and otherwise mitigate poliomyelitis and to provide immunization from the disease.The conclusion is reached that the virus of poliomyelitis is a form of the specific streptococcus, which is the agent in primary infections and in the development of the immunizing antibody.     

笼养猕猴瘫痪症防治的探讨

目的对长期笼养后肢瘫痪的猕猴,采用人工护理和药物治疗进行防治使之恢复正常。方法瘫痪猴采用科学合理的饲料配方,保证有充足的营养,笼舍保证宽大的活动空间和充足的日光,并有供其跳跃攀登活动的栖息架,按摩瘫痪肢体及功能锻炼等人工护理;同时使用维生素A、复合维生素B、维生素C和维生素D等维生素药物治疗,配合使用转移因子、干扰素、前列腺素、肾上腺皮质激素等炎症和免疫抑制药物辅助治疗。结果共实施治疗护理瘫痪猴18例,治愈率达60％,恢复良好,能正常行走活动。结论采用人工护理配合药物治疗,防治排尿粪障碍、后肢萎缩、淤血、水肿和坏死等,瘫痪猴能取得良好的治疗效果,对保护珍贵猕猴动物资源,减少因瘫痪引起猕猴的痛苦或死亡均有一定的参考价值。     

Development and validation of a model to describe root length density of maize from root counts on soil profiles

Root length density (RLD) is an important determinant of crop water and nutrient acquisition, but is difficult to measure in the field. On a soil profile, in-situ counts of root impacts per unit surface on soil profiles (NI) can be used to calculate RLD if crop-specific parameters for preferential root orientation (anisotropy) are known. An improved method for field determinations of RLD was developed and validated for maize at sites in Côte d'Ivoire and Burkina Faso. Root anisotropy was measured with cubes of undisturbed soil with 0.1 m sidelength, based on NI observed on three planes oriented perpendicularly to each other. RLD was also measured for the enclosed volume. Repetition of such measurements enabled estimation of the robustness across sites of empirical and geometric models for the relationship between RLD and NI:RLD = NI CO, with CO being the coefficient of root orientation, theoretically equals 2 for an isotropic distribution. Root systems were found to be nearly isotropic, except near the root front (0.3 to 0.5 m), where roots had a preferentially orthotropic orientation. Measured RLD was generally about 50% larger than RLD calculated from observed NI and CO, indicating that at least one of the measurement techniques had a systematic error. The ratio between measured and calculated RLD (CE), which ranged from 0.8 to 2, increased with the age of the plants and decreased with soil depth. CE was therefore introduced as an additional coefficient, resulting in RLD = NI CO CE. The empirical value for CO CE was between 2 and 5. The empirical coefficients CO and CE were the same for the sites in Cote d'Ivoire (oxisol with an iron pan at 0.6 to 0.9 m) and Burkina Faso (alfisol with an iron pan at 0.4 to 0.8 m). The model was validated with independent data sets at both sites, and gave satisfactory predictions of RLD on the basis of NI obtained from single soil planes, which can be easily measured in the field.