Miracle-dz/UniFAR-FTUs huggingface dataset:
Generation of DOPA-Producing Astrocytes by Retroviral Transduction of the Human Tyrosine Hydroxylase Gene:In VitroCharacterization andin VivoEffects in the Rat Parkinson Model

Astrocytes secreting high levels of L-3,4-dihydroxyphenylalanine (DOPA) have been generated by retrovirus-mediated transfer of the human tyrosine hydroxylase (TH) gene. Immature astrocytes obtained from prenatal rat brain were cocultured with TH virus producing psi-2 cells that had been pretreated with the mitosis inhibitor mitomycin-C. During the first week of coculture DOPA production gradually increased to reach a plateau after 7-9 days. At this time point virtually all cells were GFAP positive and over 80% of them expressed TH. DOPA production in the transduced astrocytes was largely independent of exogenous cofactor, and DOPA release into the medium was not influenced by addition of either KCl or tetrodotoxin or by removal of Ca2+ from the culture medium, indicating that the newly synthesized DOPA was constitutively released from the cells. Transplantation of the TH-transduced astrocytes to the striatum in unilaterally 6-hydroxydopamine lesioned rats reduced apomorphine-induced turning by about 50% at 2 weeks postgrafting. Microscopic analysis revealed that the transduced astrocytes survived very well after transplantation and that some of the grafted cells had migrated out, partly along blood vessels, into the surrounding striatum. TH expression was observed in cells with both the appearance of mature GFAP-positive astrocytes, as well as in more immature-looking cells. However, only a few percent of all transplanted cells maintained significant expression of the transgene, as determined by TH immuno-histochemistry. The results show that primary astrocytes may be highly useful as gene carriers for ex vivo gene therapy in the CNS. With future improvement in the gene transduction procedure for more efficient, sustained expression of the TH transgene in vivo, genetically engineered DOPA-producing astrocytes hold great promise as a tool to explore the potential of ex vivo gene therapy in Parkinson's disease.
Differential modulation by dopamine of responses evoked by excitatory amino acids in human cortex

The responses of human neocortical neurons to iontophoretic application of excitatory amino acids and their modulation by dopamine (DA) were studied in vitro. Brain slices were obtained from children undergoing surgery for intractable epilepsy. Application of N‐methyl‐D‐aspartate (NMDA) to the slices induced slow depolarizations accompanied by decreased input conductances and sustained action potentials in cortical neurons. Glutamate produced rapid depolarizations and firing with few changes in input conductances. Quisqualate also induced depolarization and firing, but input conductances increased during the rising phase of the membrane depolarization. Iontophoretic application of DA alone produced no change in membrane potential or input conductance. However, when DA was applied in conjunction with the excitatory amino acids, it produced contrasting effects. With either bath application of DA or when iontophoresis of DA preceded application of NMDA, the amplitude of the membrane depolarizations and the number of action potentials were increased, whereas the latency of these responses decreased. In contrast, DA decreased the amplitude of the depolarizations and the number of action potentials evoked by glutamate or quisqualate. The fact that DA affects responses to NMDA and glutamate or quisqualate in opposite directions is of considerable importance to the understanding of cellular mechanisms of neuromodulation and the role of DA in cognitive processing and in epilepsy. © Wiley‐Liss, Inc.
Defective regulation of mitogen-activated protein kinase activity in a 3T3 cell variant mitogenically nonresponsive to tetradecanoyl phorbol acetate

Mitogen-activated protein (MAP) kinase is a serine/threonine-specific protein kinase which is activated in response to various mitogenic agonists (e.g., epidermal growth factor, insulin, and the tumor promoter tetradecanoyl phorbol acetate [TPA]) and requires both threonine and tyrosine phosphorylation for activity. This enzyme has recently been shown to be identical or closely related to pp42, a protein which becomes tyrosine phosphorylated in response to mitogenic stimulation. Neither the kinases which regulate MAP kinase/pp42 nor the in vivo substrates for this enzyme are known. Because MAP MAP kinase is activated and phosphorylated in response both to agents which stimulate tyrosine kinase receptors and to agents which stimulate protein kinase C, a serine/threonine kinase, we have examined the regulation and phosphorylation of this enzyme in 3T3-TNR9 cells, a variant cell line partially defective in protein kinase C-mediated signalling. In this communication, we show that in the 3T3-TNR9 variant cell line, TPA does not cause the characteristically rapid phosphorylation of pp42 or the activation and phosphorylation of MAP kinase. This defective response is not due to the absence of the MAP kinase/pp42 protein itself because both tyrosine phosphorylation of MAP kinase/pp42 and its enzymatic activation could be induced by platelet-derived growth factor in the 3T3-TNR9 cells. Thus, the defect in these variant cells apparently resides in some aspect of the regulation of MAP kinase phosphorylation. Since the 3T3-TNR9 cells are also defective with respect to the TPA-induced increase in ribosomal protein S6 kinase, these in vivo results reinforce the earlier in vitro finding that MAP kinase can regulate S6 kinase activity. These findings suggest a key role for MAP kinase in a kinase cascade cascade involved in the control of cell proliferation.
Quantative Inversion based on Hyperspectral Data for Soil Salinization in the Ecological Corridor of Tarim River, Xinjiang, China

Soil salinization is regarded as the key factor that limits the growth of local vegetation at the lower reaches of the Tarim River. In order to Inverse the salinization level of surface soil, this paper attempts to adopt the following measures: soil salinization field sampling, soil salinization field hyperspectral sampling, and hyperspectral Remote sensing analysis, Finally, we used the regression model of soil salinity to develop the map of soil salinity concentration the lower reaches area of the Tarim River, with EO -1 Hyperion data. the field test has validated this method's validity and feasibility. the result shows that we would solve that problem.
Social Hierarchies: A Laboratory Study on Punishment Patterns Across Networks

We experimentally study punishment patterns across network structures, and their effect on cooperation. In a repeated public goods setting, subjects can only observe and punish their neighbors. Centralized structures (like the star network) outperform other incomplete networks and reach contribution levels like the ones observed in a complete network. Our results suggest that hierarchical network structures with a commonly observed player benefit more from sanctions not because central players punish more, but because they follow, and promote, different punishment patterns. While quasi-central players in other incomplete architectures (like the line network) retaliate, and get trapped in the vicious circle of antisocial punishment, central players in the star network do not punish back, increase their contributions when sanctioned by peripheral players, and sanction other participants in a prosocial manner. Our results illustrate recent field studies on the evolutionary prevalence of hierarchical networks. We document a network-based rationale for this positive effect in an identity-free, fully anonymous environment. (JEL C72, C91, C92, D90, H41).
Urinary incontinence – why refraining from treatment? A populationbased study

Objective To investigate why persons with urinary incontinence (UI) refrain from seeking care and treatment. Material and methods A population-based study was undertaken in which a public health survey and a specific UI questionnaire were sent to 15 360 randomly selected residents (age 18–79 years) of Örebro County, Sweden. For all persons reporting UI, the expressed wish for treatment or no treatment was analyzed in relation to relevant variables from both inquiry forms using binary logistic regression analysis. Results The response rate was 64.5%. UI was reported by 2194 persons, 1724 of whom comprised the study population. A statistically significant association was found between the degree of UI and a desire for treatment. Persons who did not experience daily leakage and those who did not perceive the leakage as troublesome or having an affect on their daily life mostly stated that they did not desire treatment. Socioeconomic or other health-related factors were not associated with desiring or not desiring treatment for UI. Conclusions Our results show that it is the perceived severity of UI that determines whether afflicted persons desire treatment or not. Other factors, relating to seeking healthcare in general, were not found to be of importance. Interventions to identify those in need of treatment for UI should primarily be directed towards those with severe symptoms.
Project among African-Americans to explore risks for schizophrenia (PAARTNERS): evidence for impairment and heritability of neurocognitive functioning in families of schizophrenia patients.

OBJECTIVE Neurocognitive impairments in schizophrenia are well replicated and widely regarded as candidate endophenotypes that may facilitate understanding of schizophrenia genetics and pathophysiology. The Project Among African-Americans to Explore Risks for Schizophrenia (PAARTNERS) aims to identify genes underlying liability to schizophrenia. The unprecedented size of its study group (N=1,872), made possible through use of a computerized neurocognitive battery, can help further investigation of the genetics of neurocognition. The current analysis evaluated two characteristics not fully addressed in prior research: 1) heritability of neurocognition in African American families and 2) relationship between neurocognition and psychopathology in families of African American probands with schizophrenia or schizoaffective disorder. METHOD Across eight data collection sites, patients with schizophrenia or schizoaffective disorder (N=610), their biological relatives (N=928), and community comparison subjects (N=334) completed a standardized diagnostic evaluation and the computerized neurocognitive battery. Performance accuracy and response time (speed) were measured separately for 10 neurocognitive domains. RESULTS The patients with schizophrenia or schizoaffective disorder exhibited less accuracy and speed in most neurocognitive domains than their relatives both with and without other psychiatric disorders, who in turn were more impaired than comparison subjects in most domains. Estimated trait heritability after inclusion of the mean effect of diagnostic status, age, and sex revealed significant heritabilities for most neurocognitive domains, with the highest for accuracy of abstraction/flexibility, verbal memory, face memory, spatial processing, and emotion processing and for speed of attention. CONCLUSION Neurocognitive functions in African American families are heritable and associated with schizophrenia. They show potential for gene-mapping studies.
Functional Effects of Rho-Kinase–Dependent Phosphorylation of Specific Sites on Cardiac Troponin

We tested the hypothesis that activation of Rho-A–dependent kinase (ROCK-II) alters cardiac myofilament response to Ca2+ by mechanisms involving phosphorylation of thin filament proteins. We determined effects of a constitutively active form of ROCK-II on ATPase activity and tension development in detergent-extracted (skinned) fiber bundles isolated from mouse left ventricular papillary muscles. ROCK-II induced a depression in maximum ATPase rate and tension, which was associated with phosphorylation of troponin T (TnT), troponin I (TnI), and myosin-binding protein C (C-protein). This effect of ROCK-II was retained in fiber bundles isolated from transgenic (TG) mice in which phosphorylation sites (S14, S15, and S19) of myosin light chain 2 were mutated to alanine. Moreover, exchange of ROCK-II–phosphorylated Tn complex with the native Tn complex in the fiber bundles resulted in inhibition of maximal Ca2+ activation of tension and ATPase activity. Mass spectrometric analysis demonstrated that ROCK-II phosphorylated cardiac TnI (cTnI) at S23, S24, and T144 and cardiac TnT (cTnT) at S278 and T287. An important role for these cTnT sites is indicated by results demonstrating that ROCK-II induced a depression in tension and ATPase activity in skinned fiber bundles from a TG model in which cTnI is replaced by slow skeletal TnI, which lacks S23 and S24 and in which T144 is replaced by proline. Our data provide the first evidence that ROCK-II phosphorylation of the Tn complex, most likely at cTnT, has an important role in functional effects of signaling through the Rho-A pathway.
The actions of calcium on the mechano‐electrical transducer current of turtle hair cells.

1. Mechano‐electrical transducer currents evoked by deflections of the hair bundle were recorded in turtle isolated hair cells under whole‐cell voltage clamp. The outcome of perfusing with solutions of reduced Ca2+ concentration was investigated. 2. The transducer current was roughly doubled by lowering the concentration of divalent cations from normal (2.2 mM‐Mg2+, 2.8 mM‐Ca2+) to 0 Mg2+, 0.5 mM‐Ca2+. No significant effects on the current's kinetics or reversal potential, or on the current‐displacement relationship, were noted. 3. If the Ca2+ concentration was lowered to 50 microM (with no Mg2+), there was about a threefold increase in the maximum current but other changes, including loss of adaptation and a decreased slope and negative shift in the current‐displacement relationship, were also observed. As a result, more than half the peak transducer current became activated at the resting position of the hair bundle compared to about a tenth in the control solution. 4. The extra changes manifest during perfusion with 50 microM‐Ca2+ had also been seen when the cell was held at positive potentials near the Ca2+ equilibrium potential. This supports the view that some consequences of reduced external Ca2+ stem from a decline in its intracellular concentration. 5. With 20 microM‐Ca2+, a standing inward current developed and the cell became unresponsive to mechanical stimuli, which may be explained by the transducer channels being fully activated at the resting position of the bundle. 6. The results are interpreted in terms of a dual action of Ca2+: an external block of the transducer channel which reduces the maximum current, and an intracellular effect on the position and slope of the current‐displacement relationship; the latter effect can be modelled by internal Ca2+ stabilizing one of the closed states of the channel. 7. During perfusion with 1 microM‐Ca2+, the holding current transiently increased but then returned to near its control level. There was a concomitant irreversible loss of sensitivity to hair bundle displacements which we suggest is due to rupture of the mechanical linkages to the transducer channel. 8. Following treatment with 1 microM‐Ca2+, single‐channel currents with an amplitude of ‐9 pA at ‐85 mV were sometimes visible in the whole‐cell recording. The probability of such channels being open could be modulated by small deflections of the hair bundle which indicates that they may be the mechano‐electrical transducer channels or conductance about 100 pS. 9. Open‐ and closed‐time distributions for the channel were fitted by single exponentials, the mean open time at rest being approximately 1 ms. The mean open time was increased and the mean closed time decreased for movements of the hair bundle towards the kinocilium. (ABSTRACT TRUNCATED AT 400 WORDS)
Magnetoencephalographic analysis of cortical activity in adults with and without Down syndrome.

BACKGROUND This preliminary study served as a pilot for an ongoing analysis of spectral power in adults with Down syndrome (DS) using a 151 channel whole head magnetoencephalography (MEG). The present study is the first step for examining and comparing cortical responses during spontaneous and task related activity in DS. METHOD Cortical responses were recorded with a 151 channel whole head MEG system in three adults with DS and three age-matched adults without DS. MEG data were obtained at rest with eyes open and during observation of point-light displays of human motion and object motion. Data from both groups were evaluated by spectral analysis. RESULTS The preliminary results showed greater alpha (8-14 Hz) power particularly in the occipital and parietal areas during the eyes open condition in the adults with DS in relation to a normal comparison group. The visual task had little effect on alpha power in the comparison group. Engaging in the visual task reduced power in alpha across all regions in the DS group to the level observed in comparisons. In the gamma band (30-50 Hz), power values were similar across both groups for the eyes open condition. In the comparison group, large reductions in gamma were observed in the occipital and bilateral temporal areas during the visual task. This change was not observed in the DS group. CONCLUSIONS The results from this pilot study suggest that MEG may be useful in characterizing task-specific changes in cortical activity in individuals with DS. Future studies with a larger group of individuals will further contribute to our understanding of the neurophysiology of Down syndrome.
Bone-Patellar Tendon-Bone Autograft versus Hamstring Tendon Autograft for Anatomical Anterior Cruciate Ligament Reconstruction with Three-Dimensional Validation of Femoral and Tibial Tunnel Positions

Abstract The purpose of this retrospective study was to first compare the clinical outcome of anatomical double-bundle (DB) anterior cruciate ligament reconstruction (ACLR) with hamstring tendon (HT) autografts and anatomical rectangular tunnel ACLR with bone-patellar tendon-bone (BPTB) autografts. Secondly, we aimed to demonstrate the quantitative locations of the femoral and tibial tunnel apertures using postoperative three-dimensional computed tomography (3D CT). Twenty-five patients underwent anatomical rectangular tunnel ACLR using BPTB grafts (Group B) and 23 patients underwent anatomical DB ACLR using HT grafts (Group H). All patients underwent subjective postoperative evaluations using the Lysholm score and Knee Injury and Osteoarthritis Outcome Score. Patients also underwent objective evaluations by the International Knee Documentation Committee score, the Lachman test, the pivot-shift test, and range of motion. In addition, we quantitatively assessed anterior knee stability using a KneeLax3 arthrometer and thigh strength. All evaluations except for thigh strength were assessed for a minimum 2 years of follow-up period. Femoral and tibial tunnel aperture locations were quantitatively evaluated postoperatively using 3D CT images in all patients. BPTB grafts showed significantly better anterior knee stability than HT grafts (0.1 mm versus 1.1 mm, p = 0.01), although there were no significant differences in other objective and all subjective evaluations between the two graft types. Morphometric analysis of femoral and tibial tunnel locations revealed that the two procedures were based on the same anatomical concept. In conclusion, BPTB grafts showed significantly better anterior knee stability than HT grafts, although no significant differences in other objective evaluations and all subjective evaluations were detected between the two graft types in anatomical ACLR. Additional 3D CT data validated the anatomical concepts of these two procedures.
KLF Family Members Regulate Intrinsic Axon Regeneration Ability

Containing Neuronal Exuberance In rats and mice, around the time of birth, neurons of the central nervous system switch from a growth mode and lose their ability to regenerate. Studying retinal ganglion cells of the rat, Moore et al. (p. 298; see the Perspective by Subang and Richardson) identified a gene, Krüppel-like factor-4 (KLF4), that seems to contribute to the switch. The KLF4 gene belongs to a family of related transcription factors that possess repressive or enhancing effects on axon growth. The combinatorial effect of this family of transcription factors before and after birth may fine-tune the ability of the neurons to extend axons. The regenerative capacity of mouse retinal ganglion cells after injury is regulated by the KLF family of transcription factors. Neurons in the central nervous system (CNS) lose their ability to regenerate early in development, but the underlying mechanisms are unknown. By screening genes developmentally regulated in retinal ganglion cells (RGCs), we identified Krüppel-like factor–4 (KLF4) as a transcriptional repressor of axon growth in RGCs and other CNS neurons. RGCs lacking KLF4 showed increased axon growth both in vitro and after optic nerve injury in vivo. Related KLF family members suppressed or enhanced axon growth to differing extents, and several growth-suppressive KLFs were up-regulated postnatally, whereas growth-enhancing KLFs were down-regulated. Thus, coordinated activities of different KLFs regulate the regenerative capacity of CNS neurons.
Developmental changes in distribution of death‐associated protein kinase mRNAs

Death‐associated protein kinase (DAP‐kinase) is Ca2+/calmodulin‐dependent serine/threonine kinase that contains ankyrin repeats and the death domain. It has been isolated as a positive mediator of interferon‐γ‐induced apoptotic cell death of HeLa cells. In order to reveal the physiological role of DAP‐kinase, the tissue distribution and developmental changes in mRNA expression of DAP‐kinase were investigated by Northern blot and in situ hybridization analyses. DAP‐kinase mRNA was predominantly expressed in brain and lung. In brain, DAP‐kinase mRNA had already appeared at embryonic day 13 (E13) and was, thereafter, detected throughout the entire embryonic period. High levels of expression were detected in proliferative and postmitotic regions within cerebral cortex, hippocampus, and cerebellar Purkinje cells. These findings suggest that DAP‐kinase may play an important role in neurogenesis where a physiological type of cell death takes place. The overall expression of DAP‐kinase mRNA in the brain gradually declined at postnatal stages, and the expression became restricted to hippocampus, in which different expression patterns were observed among rostral, central, and caudal coronal sections, suggesting that DAP‐kinase may be implicated in some neuronal functions. Furthermore, it was found that the expression of DAP‐kinase mRNA was increased prior to a certain cell death induced by transient forebrain ischemia, indicating a possible relationship between DAP‐kinase and neuronal cell death. J. Neurosci. Res. 58:674–683, 1999. © 1999 Wiley‐Liss, Inc.