Miracle-dz/UniFAR-FTUs huggingface dataset:
Ca2+–calmodulin‐dependent myosin light chain kinase is essential for activation of TRPC5 channels expressed in HEK293 cells

Mammalian homologues of Drosophila transient receptor potential (TRP) proteins are responsible for receptor‐activated Ca2+ influx in vertebrate cells. We previously reported the involvement of intracellular Ca2+ in the receptor‐mediated activation of mammalian canonical transient receptor potential 5 (TRPC5) channels. Here we investigated the role of calmodulin, an important sensor of changes in intracellular Ca2+, and its downstream cascades in the activation of recombinant TRPC5 channels in human embryonic kidney (HEK) 293 cells. Ca2+ entry through TRPC5 channels, induced upon stimulation of the G‐protein‐coupled ATP receptor, was abolished by treatment with W‐13, an inhibitor of calmodulin. ML‐9 and wortmannin, inhibitors of Ca2+–calmodulin‐dependent myosin light chain kinase (MLCK), and the expression of a dominant‐negative mutant of MLCK inhibited the TRPC5 channel activity, revealing an essential role of MLCK in maintaining TRPC5 channel activity. It is important to note that ML‐9 impaired the plasma membrane localization of TRPC5 channels. Furthermore, TRPC5 channel activity measured using the whole‐cell patch‐clamp technique was inhibited by ML‐9, whereas TRPC5 channel activity observed in the cell‐excised, inside‐out patch was unaffected by ML‐9. An antibody that recognizes phosphorylated myosin light chain (MLC) revealed that the basal level of phosphorylated MLC under unstimulated conditions was reduced by ML‐9 in HEK293 cells. These findings strongly suggest that intracellular Ca2+–calmodulin constitutively activates MLCK, thereby maintaining TRPC5 channel activity through the promotion of plasma membrane TRPC5 channel distribution under the control of phosphorylation/dephosphorylation equilibrium of MLC.
SEXUAL BEHAVIOUR IN NORMAL AND NEUROTIC FEMALES

Relationship of neurosis and sexual-behaviour has been a controversial issue to-date. This study was designed to explore (a) whether sexual dysfunctions are responsible for development of neurosis, (b) does neurosis affect sexual-behaviour. In the present study sexual-behaviour of 53 married female neurotics and 32 matched healthy controls was studied. Health subjects were screened by Corncell Medical Index. A sexual-behaviour questionnaire was administered to all subjects. Experimental subjects were enquired about the sexual behaviour at two periods (a) before the onset of neurotic illness, (b) after the co-commencement of neurotic illness. These observations were compared with those of healthy subjects as well as between the two periods. Sexual-behaviour of neurotics was no way different to that of healthy control before the onset of illness. However, after the commencement of illness experimental subjects showed significant decreases in sexual satisfaction (sexual adequacy) in comparison to their pre-illness sexual behavior as well as from that of healthy controls. These results tend to refute the first proposition of holding sexual disturbances responsible for development of neurotic-illnesses but support the notion of presence of sexual-disturbances during illness.
What do the HIRM and S‐ratio really measure in environmental magnetism?

The “hard” isothermal remanent magnetization (HIRM) and the S‐ratio are widely used in environmental magnetism to quantify the absolute and relative concentrations, respectively, of antiferromagnetic minerals (hematite and goethite) in mineral mixtures. We demonstrate that synthetic Al‐substituted hematite and goethite exhibit a wide range of coercivities, which significantly influences the HIRM and S‐ratio. These parameters are therefore not necessarily straightforward indicators of the absolute and relative concentrations of hematite/goethite. To circumvent this problem, we propose a new parameter (the L‐ratio), which is the ratio of two remanences after alternating field (AF) demagnetization of an IRM imparted in a 1 T field with a peak AF of 100 mT and 300 mT: IRMAF@300mT/IRMAF@100mT. These parameters are easily measured using modern vibrating sample or alternating gradient magnetometers. Changes in HIRM only reflect changes in the absolute concentration of hematite and/or goethite if the L‐ratio is relatively constant. Conversely, L‐ratio fluctuations indicate variable coercivities that possibly reflect changes in the source of hematite/goethite. Corresponding HIRM and S‐ratio variations should be interpreted with caution in such cases. The L‐ratio can be determined using equivalent terms depending on available instrumentation and measurement protocols. For example, the HIRM is equivalent to IRMAF@300mT. Likewise, 0.5*(SIRM + IRM−100mT), where IRM−100mT represents the remanent magnetization obtained by first saturating the sample in a high field and then applying a back‐field of −100 mT, is equivalent to IRMAF@100mT. The HIRM/[0.5*(SIRM + IRM−100mT)] ratio is therefore a suitable substitute for the L‐ratio when measurements are made with a long‐core magnetometer. The newly proposed L‐ratio is straightforward to measure on a wide range of instruments and can provide significant new insights and reduce ambiguities associated with interpretation of two widely used parameters in environmental magnetism, the HIRM and S‐ratio.
Inhibition of thyrotropin releasing hormone-mediated secretion of thyrotropin by human growth hormone.

The serum thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) was measured in ten patients with short stature prior to, during and after the administration of clinical grade human growth hormone (hGH). TRH-stimulated TSH secretion was significantly lower than baseline values after the ninth consecutive day of hGH administration, and returned to baseline levels 14 days after hGH had been discontinued. Serum thyroxine concentrations did not vary during the study, but the mean serum level of triiodothyronine increased during administration of hGH, and remained elevated after hGH had been discontinued. Clinical grade hGH was found to contain trace quantities of immunoassayable TSH. These data have not elucidated the mechanism by which clinical grade hGH inhibits TRH-mediated TSH secretion.
Stochastic analysis for crosstalk noise of coupled interconnects with process variations

This paper proposes a new approach to analyze crosstalk of coupled interconnects in the presence of process variations. The suggested method translates correlated process variations into orthogonal random variables by principle component analysis (PCA). combined with polynomial chaos expression (PCE), the technique utilizes Stochastic Collocation Method (SCM) to analyze the system response of coupled interconnects. A finite representation of interconnect crosstalk is obtained by projecting the infinite series representation onto a finite dimensional subspace. Experimental results demonstrate that the approach match well with HSPICE. The differences between the crosstalk obtained from the analytical method and HSPICE is about 2% or less. Furthermore the new approach shows good computation efficiency: much less running time has been observed over Monte Carlo SPICE simulation.
Spinal cord injury (SCI) rehabilitation: systematic analysis of communication from the biopsychosocial perspective

Abstract Purpose: Communication is powerful predictor of health-related quality of life and overall well-being, yet its role in promoting rehabilitation outcomes in spinal cord injury (SCI) is rarely mentioned. This article systematically analyzes and synthesizes literature from multiple disciplines according to a biopsychosocial perspective, providing an evidence base for clinical practice and clear direction for future research. Method: Systematic literature review and analysis, incorporating mapping to International Classification of Functioning, Disability and Health (ICF) codes. Results: In total 4338 entries were retrieved from CINAHL, PsychInfo, Medline, PubMed and SpeechBite databases for the period 1990–2014. A total of 115 treatment and observational studies (quantitative and qualitative) detailed aspects of communication according to structure, function, activity, participation and environmental factors; evident of the complex interactions between communicative function with daily living after SCI. Conclusions: Communication is a relative strength in SCI, key to empowerment, independence, social interaction, and well-being, yet its potential to enhance SCI rehabilitation outcomes remains largely underexplored and untapped. Through elucidating interactions between communication and functioning, the adapted ICF framework affords clinicians and researchers insight into areas of intervention most likely to result in widespread gains. Conscious consideration should be given to the role of communication, within an integrative, strengths-based, multidisciplinary approach to clinical practice and future research. Implications for Rehabilitation Communication fosters empowerment, independence and greater participation in life roles; recognized as a powerful predictor of health-related quality of life and overall well-being. The ICF framework elucidates influences to communicative function, and components which are influenced by communication, providing valuable insight for clinicians and researchers. Therapeutic and research endeavors guided by existing ICF core sets are at risk of failing to consider communication, thereby limiting rehabilitation outcomes. Tapping the potential of communication as a relative strength within SCI rehabilitation holds considerable promise, within integrative, strengths-based, multidisciplinary approaches to clinical practice and future research.
Order and flexibility in the motion of fish schools.

The coexistence of order and flexibility in the motion of fish schools was studied by using a simple numerical model and a computer simulation. The numerical model is based on behavioral rules for individuals in the school by considering attraction, repulsion, and parallel-orientation behavior. Each individual follows the same rules and makes school movements. The simulation results show that school order and flexibility are affected by the number of neighbors interacting with an individual in the school and by the randomness of individual motion. Increase in the number of interacting neighbors leads to high order, especially when the number increases from a low value (between one and three). An optimal number of interacting neighbors exists that is relatively low (two or three) for high flexibility, indicating that a fish needs only to pay attention to a few neighbors to realize both order and flexibility. The low randomness of individual motion benefits both order and flexibility. These results indicate that schooling fish have evolved specialized ability for establishing both school order and flexibility.
Allogeneic Stem Cell Transplantation for FLT3-Mutated Acute Myeloid Leukemia: In vivo T-Cell Depletion and Posttransplant Sorafenib Maintenance Improve Survival. A Retrospective Acute Leukemia Working Party-European Society for Blood and Marrow Transplant Study

Acute myeloid leukemia (AML) with FLT3-mutation carries a poor prognosis, and allogeneic stem cell transplantation (allo-SCT) is recommended at first complete remission (CR1). We assessed 462 adults (median age 50 years) with FLT3-mutated AML allografted between 2010 and 2015 from a matched related (40%), unrelated (49%), or haploidentical donor (11%). The median follow-up of alive patients was 39 months. Day-100 acute graft versus host disease (GVHD) grades II–IV and III–IV were encountered in 26% and 9%, whereas the 2-year incidence of chronic and extensive chronic GVHD were 34% and 16%, respectively. The 2-year incidences of relapse and nonrelapse mortality were 34% and 15%, respectively. The 2-year leukemia-free survival, overall survival (OS), and GVHD relapse-free survival (GRFS) were 51%, 59%, and 38%, respectively. In multivariate analysis, NPM1-mutation, transplantation in CR1, in vivo T-cell depletion, and posttransplant sorafenib improved OS, whereas more than one induction (late CR1) negatively affected OS. Similarly, NPM1-mutation, a haploidentical donor, T-cell depletion, and sorafenib maintenance improved GRFS, whereas late CR1 or persistent disease negatively affected it. In conclusion, FLT3-mutated AML remains a challenge even following allo-SCT. In vivo T-cell depletion and posttransplant sorafenib significantly improve OS and GRFS, and may be considered as standard of care.
Calmodulin triggers the resumption of meiosis in amphibian oocytes

The calcium-binding protein, calmodulin, has been purified from Xenopus laevis oocytes. This 18,500-dalton protein, pl 4.3, has two high- affinity calcium-binding sites per mole protein having a dissociation constant of 2.8 x 10(-6) M. Full-grown Xenopus oocytes, arrested in late G2 of the meiotic cell cycle, resumed meiosis when microinjected with 60-80 ng (3-4 pmol) of calmodulin in the form of a calcium- calmodulin complex. The timing of the meiotic events in these recipient oocytes was the same as that normally induced by progesterone. Xenopus ovarian calmodulin stimulated bovine brain phosphodiesterase (PDE) 3- to 10-fold in a calcium-dependent manner, but it had no apparent effect on ovarian PDE activity. A calcium-calmodulin-dependent protein kinase has been isolated from Xenopus oocytes using a calmodulin-Sepharose 4B affinity column. The possible role for this kinase in regulating the G2- M transition in oocytes has been discussed.
What is “Odd” in Posner's Location-cueing Paradigm? Neural Responses to Unexpected Location and Feature Changes Compared

Within the parietal cortex, the temporo-parietal junction (TPJ) and the intraparietal sulcus (IPS) seem to be involved in both spatial and nonspatial functions: Both areas are activated when misleading information is provided by invalid spatial cues in Posner's location-cueing paradigm, but also when infrequent deviant stimuli are presented within a series of standard events. In the present study, we used functional magnetic resonance imaging to investigate the distinct and shared brain responses to (i) invalidly cued targets requiring attentional reorienting, and (ii) to target stimuli deviating in color and orientation leading to an oddball-like distraction effect. Both unexpected location and feature changes were accompanied by a significant slowing of manual reaction times. Bilateral TPJ and right superior parietal lobe (SPL) activation was observed in response to invalidly as compared to validly cued targets. In contrast, the bilateral inferior occipito-temporal cortex, the left inferior parietal cortex, right frontal areas, and the cerebellum showed stronger activation in response to deviant than to standard targets. Common activations were observed in the right angular gyrus along the IPS and in the right inferior frontal gyrus. We conclude that the superior parietal and temporo-parietal activations observed here as well as previously in location-cueing paradigms do not merely reflect the detection and processing of unexpected stimuli. Furthermore, our data suggest that the right IPS and the inferior frontal gyrus are involved in attentional selection and distractor processing of both spatial and nonspatial features.
Muscle Dystroglycan Organizes the Postsynapse and Regulates Presynaptic Neurotransmitter Release at the Drosophila Neuromuscular Junction

Background The Dystrophin-glycoprotein complex (DGC) comprises dystrophin, dystroglycan, sarcoglycan, dystrobrevin and syntrophin subunits. In muscle fibers, it is thought to provide an essential mechanical link between the intracellular cytoskeleton and the extracellular matrix and to protect the sarcolemma during muscle contraction. Mutations affecting the DGC cause muscular dystrophies. Most members of the DGC are also concentrated at the neuromuscular junction (NMJ), where their deficiency is often associated with NMJ structural defects. Hence, synaptic dysfunction may also intervene in the pathology of dystrophic muscles. Dystroglycan is a central component of the DGC because it establishes a link between the extracellular matrix and Dystrophin. In this study, we focused on the synaptic role of Dystroglycan (Dg) in Drosophila. Methodology/Principal Findings We show that Dg was concentrated postsynaptically at the glutamatergic NMJ, where, like in vertebrates, it controls the concentration of synaptic Laminin and Dystrophin homologues. We also found that synaptic Dg controlled the amount of postsynaptic 4.1 protein Coracle and alpha-Spectrin, as well as the relative subunit composition of glutamate receptors. In addition, both Dystrophin and Coracle were required for normal Dg concentration at the synapse. In electrophysiological recordings, loss of postsynaptic Dg did not affect postsynaptic response, but, surprisingly, led to a decrease in glutamate release from the presynaptic site. Conclusion/Significance Altogether, our study illustrates a conservation of DGC composition and interactions between Drosophila and vertebrates at the synapse, highlights new proteins associated with this complex and suggests an unsuspected trans-synaptic function of Dg.
The Temporal Evolution of Feedback Gains Rapidly Update to Task Demands

Recent theoretical frameworks such as optimal feedback control suggest that feedback gains should modulate throughout a movement and be tuned to task demands. Here we measured the visuomotor feedback gain throughout the course of movements made to “near” or “far” targets in human subjects. The visuomotor gain showed a systematic modulation over the time course of the reach, with the gain peaking at the middle of the movement and dropping rapidly as the target is approached. This modulation depends primarily on the proportion of the movement remaining, rather than hand position, suggesting that the modulation is sensitive to task demands. Model-predictive control suggests that the gains should be continuously recomputed throughout a movement. To test this, we investigated whether feedback gains update when the task goal is altered during a movement, that is when the target of the reach jumped. We measured the visuomotor gain either simultaneously with the jump or 100 ms after the jump. The visuomotor gain nonspecifically reduced for all target jumps when measured synchronously with the jump. However, the visuomotor gain 100 ms later showed an appropriate modulation for the revised task goal by increasing for jumps that increased the distance to the target and reducing for jumps that decreased the distance. We conclude that visuomotor feedback gain shows a temporal evolution related to task demands and that this evolution can be flexibly recomputed within 100 ms to accommodate online modifications to task goals.
Strain-Dependent Anterior Segment Dysgenesis and Progression to Glaucoma in Col4a1 Mutant Mice.

PURPOSE Mutations in the gene encoding collagen type IV alpha 1 (COL4A1) cause multisystem disorders including anterior segment dysgenesis (ASD) and optic nerve hypoplasia. The penetrance and severity of individual phenotypes depends on genetic context. Here, we tested the effects of a Col4a1 mutation in two different genetic backgrounds to compare how genetic context influences ocular dysgenesis, IOP, and progression to glaucoma. METHODS Col4a1 mutant mice maintained on a C57BL/6J background were crossed to either 129S6/SvEvTac or CAST/EiJ and the F1 progeny were analyzed by slit-lamp biomicroscopy and optical coherence tomography. We also measured IOPs and compared tissue sections of eyes and optic nerves. RESULTS We found that the CAST/EiJ inbred strain has a relatively uniform and profound suppression on the effects of Col4a1 mutation and that mutant CASTB6F1 mice were generally only very mildly affected. In contrast, mutant 129B6F1 mice had more variable and severe ASD and IOP dysregulation that were associated with glaucomatous signs including lost or damaged retinal ganglion cell axons and excavation of the optic nerve head. CONCLUSIONS Ocular defects in Col4a1 mutant mice model ASD and glaucoma that are observed in a subset of patients with COL4A1 mutations. We demonstrate that different inbred strains of mice give graded severities of ASD and we detected elevated IOP and glaucomatous damage in 129B6F1, but not CASTB6F1 mice that carried a Col4a1 mutation. These data demonstrate that genetic context differences are one factor that may contribute to the variable penetrance and severity of ASD and glaucoma in patients with COL4A1 mutations.
Dead reckoning based target tracking in wireless sensor networks

Target tracking is one of the key applications of Wireless Sensor Networks (WSNs) that forms basis for numerous other applications. Real situations in tracking, such as an unexpected change in the mobile event's direction, failure of event detection, or transmission failure of an error message may result into erroneous tracking information. Thus, in order to prevent and handle errors effectively, it is required that tracking algorithm must incorporate error avoidance and error correction phase. In this paper we present Dead Reckoning (DR) based target tracking protocol. DR determines target's present position by projecting its past positions and speed over elapsed time and known target's path. Moreover, it inherits the functionality of error correction and error avoidance using a position fix technique. The performance of DR based tracking is also discussed, which confirms the efficacy of the algorithm.
Apolipoprotein M Inhibits Angiogenic and Inflammatory Response by Sphingosine 1-Phosphate on Retinal Pigment Epithelium Cells

Sphingosine 1-phosphate (S1P) is a potent lipid mediator that modulates inflammatory responses and proangiogenic factors. It has been suggested that S1P upregulates choroidal neovascularization (CNV) and may be deeply involved in the pathogenesis of exudative age-related macular degeneration (AMD). Recent studies have suggested that apolipoprotein M (ApoM), a carrier protein for S1P, modulates the biological properties of S1P in the pathogenesis of atherosclerosis. However, the role of ApoM/S1P in AMD has not been explored. We investigated the effect of S1P on proangiogenic factors in human retinal pigment epithelium (RPE) cell lines in vitro. S1P promoted the expression of vascular endothelial growth factor in RPE cells. Hypoxia inducible factor-1α expression was also upregulated. These S1P-induced enhancements in growth factors and chemotactic cytokines in RPE cells were significantly inhibited by ApoM treatment. Additionally, in vivo experiments using a laser-induced CNV murine model demonstrated that intravitreal ApoM injection significantly reduced the progression of CNV formation. Although the detailed mechanisms remain to be elucidated, the present results provide a novel potential therapeutic target for AMD, and demonstrate a suppressive role for ApoM and S1P in the pathology of CNV progression.
2D J‐resolved spiral spectroscopic imaging at 7 T: Application to mobile lipid mapping in a rat glioma

Lactate (Lac) and mobile lipids (Lip), which are present in rat gliomas, are difficult to map because their 1H resonances overlap in the 1.3 ppm region. 2D J‐resolved spectroscopy enables proper separation of the two resonance lines. To obtain high‐spatial‐resolution mapping of Lac and Lip resonances within a reasonable experiment time, we coupled 2D J‐resolved spectroscopy with a fast spectroscopic imaging (SI) method, based on an out‐and‐in spiral k‐space description. The method was applied to a rat glioma at 7 T, and Lac and Lip maps were reconstructed. The duration of SI (2D spatial, 2D spectral) was 64 min for a theoretical in‐plane resolution of 1 × 1 mm, and a slice thickness of 2 mm (voxel size 8.2 μl, taking into account the point‐spread function (PSF)). Magn Reson Med 52:658–662, 2004. © 2004 Wiley‐Liss, Inc.