Both 5' and 3' flanks regulate Zebrafish brain-derived neurotrophic factor gene expression

Background  

Precise control of developmental and cell-specific expression of the brain-derived neurotrophic factor (BDNF) gene is essential for normal neuronal development and the diverse functions of BDNF in the adult organism. We previously showed that the zebrafish BDNF gene has multiple promoters. The complexity of the promoter structure and the mechanisms that mediate developmental and cell-specific expression are still incompletely understood.     

Dyskinesia and brain-derived neurotrophic factor levels after long-term levodopa and nicotinic receptor agonist treatments in female mice with near-total unilateral dopaminergic denervation

Background

The treatment of Parkinson’s disease is often complicated by levodopa-induced dyskinesia (LID). Nicotinic acetylcholine receptor agonists can alleviate LID in animal models but may be less effective in conditions of severe dopaminergic denervation. While the mechanisms of LID remain incompletely understood, elevated corticostriatal levels of the brain-derived neurotrophic factor (BDNF) have been suggested to play a role. Here, female mice with near-total unilateral 6-hydroxydopamine-induced nigrostriatal lesions were chronically treated with levodopa, and the effects of the α7 nicotinic receptor partial agonist AZD0328 and nicotine on LID were assessed. At the end of the experiment, BDNF protein levels in the prefrontal cortex and striatum were measured.

Results

Five-day treatments with three escalating doses of AZD0328 and a 10-week treatment with nicotine failed to alleviate LID. BDNF levels in the lesioned striatum correlated positively with LID severity, but no evidence was found for a levodopa-induced elevation of corticostriatal BDNF in the lesioned hemisphere. The nicotine treatment decreased BDNF levels in the prefrontal cortex but had no effect on striatal BDNF.

Conclusions

The findings suggest that treatment of LID with nicotinic agonists may lose its effectiveness as the disease progresses, represent further evidence for a role for BDNF in LID, and expand previous knowledge on the effects of long-term nicotine treatment on BDNF.

     

Functional MRI of motor and sensory activation in the human spinal cord

MR imaging of the cervical spinal cord was carried out on volunteers during alternated rest and either motor or sensory stimulation of one hand, in order to detect image intensity changes arising concomitant to neuronal activity. We employed both spin-echo and gradient-echo echo-planar imaging, on the right and left hands, with both symmetric and asymmetric temporal patterns of rest and stimulation. Intensity changes correlated with the time course of stimulation were consistently detected, and the magnitude of the intensity changes depended on the duration of stimulation. The activated regions in the spinal cord extended along a column on the side of the body being stimulated and included localized regions on the contralateral side, in agreement with the neural anatomy.     

Difference in trafficking of brain-derived neurotrophic factor between axons and dendrites of cortical neurons,revealed by live-cell imaging

Background  

Brain-derived neurotrophic factor (BDNF), which is sorted into a regulated secretory pathway of neurons, is supposed to act retrogradely through dendrites on presynaptic neurons or anterogradely through axons on postsynaptic neurons. Depending on which is the case, the pattern and direction of trafficking of BDNF in dendrites and axons are expected to be different. To address this issue, we analyzed movements of green fluorescent protein (GFP)-tagged BDNF in axons and dendrites of living cortical neurons by time-lapse imaging. In part of the experiments, the expression of BDNF tagged with cyan fluorescent protein (CFP) was compared with that of nerve growth factor (NGF) tagged with yellow fluorescent protein (YFP), to see whether fluorescent protein-tagged BDNF is expressed in a manner specific to this neurotrophin.     

Differential expression of Cathepsin S and X in the spinal cord of a rat neuropathic pain model

Background

Proteoglycan (PG) in the extracellular matrix (ECM) of the central nervous system (CNS) may act as a barrier for neurite elongation in a growth tract, and regulate other characteristics collectively defined as structural neural plasticity. Proteolytic cleavage of PGs appears to alter the environment to one favoring plasticity and growth. Brevican belongs to the lectican family of aggregating, chondroitin sulfate (CS)-bearing PGs, and it modulates neurite outgrowth and synaptogenesis. Several ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) are glutamyl-endopeptidases that proteolytically cleave brevican. The purpose of this study was to localize regions of adult CNS that contain a proteolytic-derived fragment of brevican which bears the ADAMTS-cleaved neoepitope sequence. These regions were compared to areas of Wisteria floribunda agglutin (WFA) reactivity, a common reagent used to detect "perineuronal nets" (PNNs) of intact matrix and a marker which is thought to label regions of relative neural stability.

Results

WFA reactivity was found primarily as PNNs, whereas brevican and the ADAMTS-cleaved fragment of brevican were more broadly distributed in neuropil, and in particular regions localized to PNNs. One example is hippocampus where the ADAMTS-cleaved brevican fragment is found surrounding pyramidal neurons, in neuropil of stratum oriens/radiatum and the lacunosum moleculare. The fragment was less abundant in the molecular layer of the dentate gyrus. Mostly PNNs of scattered interneurons along the pyramidal layer were identified by WFA. In lateral thalamus, the reticular thalamic nucleus stained abundantly with WFA whereas ventral posterior nuclei were markedly immunopositive for ADAMTS-cleaved brevican. Using Western blotting techniques, no common species were reactive for brevican and WFA.

Conclusion

In general, a marked discordance was observed in the regional localization between WFA and brevican or the ADAMTS-derived N-terminal fragment of brevican. Functionally, this difference may correspond to regions with varied prevalence for neural stability/plasticity.     

激光脉冲时域整形及其对发射度的改善效果

利用脉冲堆积法对驱动激光脉冲进行了时域整形,并利用条纹相机测量到了理想的整形结果。在脉冲堆积法的基础上,给出了近似椭球体整形的方案。模拟结果表明：利用脉冲堆积法整形后得到激光脉冲驱动光阴极可以获得更小的发射度;对于测量到的半高全宽（FWHM）为3.82 ps的脉冲,8个子脉冲堆积比4个子脉冲堆积更为有利;此外,对激光脉冲作近似椭球体整形可以进一步降低束流发射度。     

Microstructure of aluminium-copper thin films and its relation to electromigration

The microstructure of polycrystalline aluminium — 7·6 wt % copper thin films evaporated from the starting Al-Cu alloy was studied using electron microscopy and microanalysis. The structural properties of films were confronted with electromigration lifetime measurements of Al-Cu thin film conductors. In the films Al₂Cu precipitates were observed. Thermodynamically stable -Al₂Cu precipitates were found at grain boundaries, triple points and on the film surface. Within the grains -Al₂Cu precipitates were detected. When the temperature of deposition and/or the time of annealing of the films at 480 °C in nitrogen increased, the growth of grains and of the total volume of the precipitate phase was observed. Under these conditions precipitates tended to grow preferentially at the film surface and they ceased to influence the grain size distribution. The distribution approached then the log-normal distribution function. With regard to the structural investigations it is anticipated that the best electromigration resistance among the studied samples should possess conductors deposited at 250 °C as well as conductors deposited at 150 °C and 250 °C and annealed 10 min at 480 °C. The lifetimes of conductors having this type of microstructure and tested at the current density of 3×10⁶ A/cm² had values of 210÷3500 hrs, corresponding to the testing temperature of 150 °C. Higher lifetimes were observed with wider (20 m) and shortest (120 m) conductors encapsulated in packages filled with nitrogen. The activation energy for the failure process was 0·65 eV in this case.     

激光脉冲时域整形及其对发射度的改善效果

 利用脉冲堆积法对驱动激光脉冲进行了时域整形,并利用条纹相机测量到了理想的整形结果。在脉冲堆积法的基础上,给出了近似椭球体整形的方案。模拟结果表明：利用脉冲堆积法整形后得到激光脉冲驱动光阴极可以获得更小的发射度;对于测量到的半高全宽（FWHM）为3.82 ps的脉冲,8个子脉冲堆积比4个子脉冲堆积更为有利;此外,对激光脉冲作近似椭球体整形可以进一步降低束流发射度。     

A new class of integrable systems and its relation to solitons

We present and study a class of finite-dimensional integrable systems that may be viewed as relativistic generalizations of the Calogero-Moser systems. For special values of the coupling constants we obtain N-particle systems that are intimately related to the N-soliton solutions of the sine-Gordon and Korteweg-de Vries equations, among other ones.     

Sensorimotor adaptation to feedback perturbations of vowel acoustics and its relation to perception

The role of auditory feedback in speech motor control was explored in three related experiments. Experiment 1 investigated auditory sensorimotor adaptation: the process by which speakers alter their speech production to compensate for perturbations of auditory feedback. When the first formant frequency (F1) was shifted in the feedback heard by subjects as they produced vowels in consonant-vowel-consonant (CVC) words, the subjects' vowels demonstrated compensatory formant shifts that were maintained when auditory feedback was subsequently masked by noise-evidence of adaptation. Experiment 2 investigated auditory discrimination of synthetic vowel stimuli differing in F1 frequency, using the same subjects. Those with more acute F1 discrimination had compensated more to F1 perturbation. Experiment 3 consisted of simulations with the directions into velocities of articulators model of speech motor planning, which showed that the model can account for key aspects of compensation. In the model, movement goals for vowels are regions in auditory space; perturbation of auditory feedback invokes auditory feedback control mechanisms that correct for the perturbation, which in turn causes updating of feedforward commands to incorporate these corrections. The relation between speaker acuity and amount of compensation to auditory perturbation is mediated by the size of speakers' auditory goal regions, with more acute speakers having smaller goal regions.     

The doubly-magic character of146Gd and its relation to208Pb

Recent experiments indicate the possibility of a doubly-magic character for the nucleus¹⁴⁶Gd (Z=64, N=82). In this work the results of a large-scale shell-model study on the nucleus¹⁴⁶Gd and its neighbouring nuclei¹⁴⁵Eu,¹⁴⁵Gd,¹⁴⁷Gd and¹⁴⁷Tb are presented. The configurations taken into account include up to 2p - 2h excitations for protons and/or neutrons. The calculated spectra and static moments are compared with the experimental data. Finally, the present results on shell closure in¹⁴⁶Gd are discussed in connection with those derived from a similar approach applied to the well-known doubly-magic nucleus²⁰⁸Pb.     

A model of population genetics and its mathematical relation to quantum theory

A basic model used in population genetics is motivated and it is shown how the resulting theory has a mathematical complexity equivalent to that of non-relativistic one-particle quantum mechanics. For the model in question, it is shown that a Schrödinger-like equation underlies the dynamics with the main difference that the time derivative term lacks a coefficient of i = ¡ -1. A number of special cases of the model are analysed, including one that makes connections with a topic of current interest in theoretical physics.     

The structure of Heesch groups and its relation to material property tensors

The magnetic crystal point groups (Heesch groups) are classified according to their structure with respect to the three inversion operations: space, time, and total inversion. Accordingly the tensors are classified by the irreducible representations of the full inversion group. The groups and tensors are considered under the action of the elements A_i of the group of automorphisms of the full inversion group. The following correspondence theorem is proved: The matrix form of the tensor representation T of the group G coincides with the matrix form of the representation A_iT of the group A_iG. The theorem gives a clear explanation of the so-called “magic numbers” and provides a suitable short cut for the calculation and tabulation of material property tensors.     

Enlargement of the supraglottal cavity and its relation to stop consonant voicing

Measurements were made of saggital plane movements of the larynx, soft palate, and portions of the tongue, from a high-speed cinefluorographic film of utterances produced by one adult male speaker of American English. These measures were then used to approximate the temporal variations in supraglottal cavity volume during the closures of voiced and voiceless stop consonants. All data were subsequently related to a synchronous acoustic recording of the utterances. Instances of /p,t,k/ were always accompanied by silent closures, and sometimes accompanied by decreases in supraglottal volume. In contrast, instances of /b,d,g/ were always accompanied both by significant intervals of vocal fold vibration during closure, and relatively large increases in supraglottal volume. However, the magnitudes of volume increments during the voiced stops, and the means by which those increments were achieved, differed considerably across place of articulation and phonetic environment. These results are discussed in the context of a well-known model of the breath-stream control mechanism, and their relevance for a general theory of speech motor control is considered.     

The effect of mesenchymal stem cell transplantation on the recovery of bladder and hindlimb function after spinal cord contusion in rats

Background  

Mesenchymal stem cells are widely used for transplantation into the injured spinal cord in vivo model and for safety, many human clinical trials are continuing to promote improvements of motor and sensory functions after spinal cord injury. Yet the exact mechanism for these improvements remains undefined. Neurogenic bladder following spinal cord injury is the main problem decreasing the quality of life for patients with spinal cord injury, but there are no clear data using stem cell transplantation for the improvement of neurogenic bladder for in vivo studies and the clinical setting.     

Correlating magnetic resonance imaging markers of axonal injury and demyelination in motor impairment secondary to stroke and multiple sclerosis

The primary pathological mechanisms in stroke and multiple sclerosis (MS) are very different but in both diseases, impairment may arise from a final common pathway of axonal damage. We aimed to examine the relationship between motor impairment, magnetisation transfer ratio (MTR) (an index of demyelination), and N-acetyl aspartate (NAA) loss (an index of axonal injury) localised to the descending motor pathways in stroke and MS. Twelve patients between 1 and 10 months after first ischaemic stroke causing a motor deficit and 12 patients with stable MS with asymmetric motor deficit were examined. T(2)-weighted imaging of the brain together with MTR and proton (voxel 1.5x2x2 cm(3)) MRS localised to the posterior limb of the internal capsule were performed and correlated to a composite motor deficit score. MTR and NAA in the internal capsule were reduced in both stroke and MS patients compared to controls. NAA loss correlated with motor deficit score in both stroke and MS (p<0.001 and p = 0.04, respectively). Correlations were seen between MTR and motor deficit (p<0.001) MTR and NAA loss (p <0.001) in stroke patients but not in MS patients. Axonal injury in the descending motor tracts would appear to be an important determinant of motor impairment in both stroke and MS. In stroke, MTR measures of demyelination are closely related to axonal damage and thus also correlate with motor deficit. However in MS, MTR measures of demyelination do not correlate with NAA loss or motor deficit suggesting that demyelination and gliosis may occur independently of axonal damage and are less closely linked with functional impairment.