Miracle-dz/UniFAR-FTUs huggingface dataset:
TRPC6 channel‐mediated neurite outgrowth in PC12 cells and hippocampal neurons involves activation of RAS/MEK/ERK, PI3K, and CAMKIV signaling

The non‐selective cationic transient receptor canonical 6 (TRPC6) channels are involved in synaptic plasticity changes ranging from dendritic growth, spine morphology changes and increase in excitatory synapses. We previously showed that the TRPC6 activator hyperforin, the active antidepressant component of St. John's wort, induces neuritic outgrowth and spine morphology changes in PC12 cells and hippocampal CA1 neurons. However, the signaling cascade that transmits the hyperforin‐induced transient rise in intracellular calcium into neuritic outgrowth is not yet fully understood. Several signaling pathways are involved in calcium transient‐mediated changes in synaptic plasticity, ranging from calmodulin‐mediated Ras‐induced signaling cascades comprising the mitogen‐activated protein kinase, PI3K signal transduction pathways as well as Ca2+/calmodulin‐dependent protein kinase II (CAMKII) and CAMKIV. We show that several mechanisms are involved in TRPC6‐mediated synaptic plasticity changes in PC12 cells and primary hippocampal neurons. Influx of calcium via TRPC6 channels activates different pathways including Ras/mitogen‐activated protein kinase/extracellular signal‐regulated kinases, phosphatidylinositide 3‐kinase/protein kinase B, and CAMKIV in both cell types, leading to cAMP‐response element binding protein phosphorylation. These findings are interesting not only in terms of the downstream targets of TRPC6 channels but also because of their potential to facilitate further understanding of St. John's wort extract‐mediated antidepressant activity.
Transurethral Polyacrylamide Hydrogel Injection Therapy in Women Not Eligible for Midurethral Sling Surgery

Objectives This study aims to determine the effects of transurethral polyacrylamide hydrogel injection in patients considered ineligible for midurethral sling surgery. Methods In this prospective observational study, 81 patients received treatment with transurethral polyacrylamide hydrogel injection. Patients were considered ineligible for placement of a midurethral sling based on significant comorbidity (48%), 1 or more previously failed invasive treatments (16%), mixed urinary incontinence (27%), continuous incontinence (5%), or previous pelvic radiation therapy (4%). Longitudinal assessment of subjective treatment outcomes was performed using the validated Urinary Distress Inventory (UDI) and the Pelvic Floor Impact Questionnaire at baseline, 2, and 6 months. To deal with repeated measurements, mixed linear models were used to assess changes in the outcomes over time. Results There was a significant improvement in the overall UDI score from baseline to month 2 follow-up (FU) (P<0.001). No major differences between the month 2 and 6 FUs were observed. The largest difference in effect was observed for the irritative and stress subscales. Twenty-five patients (33%) requested a second injection at the month 2 FU visit. At month 6 FU, the UDI scores for patients having had only 1 injection were largely unchanged, whereas all UDI domains worsened further for patients having had a second injection at the month 2 visit. After the injection, there were 3 minor adverse events (3.7%) and no serious adverse events. Conclusions In patients considered ineligible for midurethral sling surgery, transurethral injection with polyacrylamide hydrogel may alleviate urinary incontinence symptoms. Repeat injections did not improve outcomes in this complicated group of patients.
The Influence of Four‐Bar Linkage Knees on Prosthetic Swing‐Phase Floor Clearance

ABSTRACT Four-bar linkage knees provide greater toe clearance during the swing phase of walking than do single-axis knees. The authors developed a computer model of a transfemoral prosthesis that allowed the kinematics of commercially available four-bar linkage knees and a single-axis knee to be simulated so legshortening could be characterized. A plot of hip-toe distance versus knee-flexion angle demonstrated fourbar knees are able to shorten the limb with less knee flexion than is needed using a single-axis knee. For a hip-knee angle combination at the time of minimum toe clearance during normal walking, contour plots revealed the four-bar knees have 0.9–3.2 cm greater toe clearance than do single-axis knees.
Regulation of DNA methylation by ethanol induces tissue plasminogen activator expression in astrocytes

Alcohol exposure affects neuronal plasticity in the adult and developing brain. Astrocytes play a major role in modulating neuronal plasticity and are a target of ethanol. Tissue plasminogen activator (tPA) is involved in modulating neuronal plasticity by degrading the extracellular matrix proteins including fibronectin and laminin and is up‐regulated by ethanol in vivo. In this study we explored the hypothesis that ethanol affects DNA methylation in astrocytes thereby increasing expression and release of tPA. It was found that ethanol increased tPA mRNA levels, an effect mimicked by an inhibitor of DNA methyltransferase (DNMT) activity. Ethanol also increased tPA protein expression and release, and inhibited DNMT activity with a corresponding decrease in DNA methylation levels of the tPA promoter. Furthermore, it was observed that protein levels of DNMT3A, but not DNMT1, were reduced in astrocytes after ethanol exposure. These novel studies show that ethanol inhibits DNA methylation in astrocytes leading to increased tPA expression and release; this effect may be involved in astrocyte‐mediated inhibition of neuronal plasticity by alcohol.
Ultrastructure of the antennal sensilla of the cockroach‐egg parasitoid, Tetrastichus hagenowii (Hymenoptera: Eulophidae)

Eggs of a number of cockroach species are parasitized by Tetrastichus hagenowii. The ultrastructure of the sensilla on the antennae of females and males was examined by scanning and transmission electron microscopy. The females have two types of multiporous plate sensilla while the males have only one. Type 1 is found in females and males and has a relatively thin cuticular wall and many pores, while type 2 is found only in females and has a relatively thick cuticular wall and few pores. Both sexes have nonporous, thick‐walled, socketed hairs; multiporous, nonsocketed hairs; multiporous, thick‐walled pegs; and terminal hairs. In addition, males have multiporous, nonsocketed, long hairs. The sensilla are similar, in many respects, to the sensilla of other chalcid parasitoids. The antennal sensilla of female T. hagenowii are probably involved in ovipositional behavior. The multiporous, long hairs of the male possibly receive stimuli during mating behavior A chemoreceptive function is proposed for the multiporous plate sensilla.
Interdisciplinary Collaborative Goal Planning in a Post-Acute Neurological Setting: A Qualitative Study

The aim of this qualitative study was to explore the use of interdisciplinary collaborative goal planning from the perspective of patients, their relatives and professional staff. Eighteen patients and their relatives who had been involved in collaborative goal planning were interviewed individually after the patient was discharged from the ward of a neurological rehabilitation hospital. The members of the interdisciplinary team responsible for implementing the goal planning process were also interviewed. The findings showed that the majority of the patients and their relatives valued highly the opportunity to become actively involved in their care and discussed the impact of this on motivation, perceptions of control and freedom in decision making. The professional staff also identified benefits, which included giving clarification and direction to treatment and further opportunities for patient-centred practice. Challenges emerged as well, including the question of how to implement collaborative goal planning with people with severe language or cognitive impairment, those with poor insight or those in low awareness states. Further consideration of the issues raised is recommended as a means to promote patient-centred care.
Activation of rhodopsin gene transcription in cultured retinal precursors of chicken embryo: role of Ca2+ signaling and hyperpolarization‐activated cation channels

This study reports that the spontaneous 50‐fold activation of rhodopsin gene transcription, observed in cultured retinal precursors from 13‐day chicken embryo, relies on a Ca2+‐dependent mechanism. Activation of a transiently transfected rhodopsin promoter (luciferase reporter) in these cells was inhibited (60%) by cotransfection of a dominant‐negative form of the cAMP‐responsive element‐binding protein. Both rhodopsin promoter activity and rhodopsin mRNA accumulation were blocked by Ca2+/calmodulin‐dependent kinase II inhibitors, but not by protein kinase A inhibitors, suggesting a role of Ca2+ rather than cAMP. This was confirmed by the inhibitory effect of general and T‐type selective Ca2+ channel blockers. Oscillations in Ca2+ fluorescence (Fluo8) could be observed in 1/10 cells that activated the rhodopsin promoter (DsRed reporter). A robust and reversible inhibition of rhodopsin gene transcription by ZD7288 indicated a role of hyperpolarization‐activated channels (HCN). Cellular localization and developmental expression of HCN1 were compatible with a role in the onset of rhodopsin gene transcription. Together, the data suggest that the spontaneous activation of rhodopsin gene transcription in cultured retinal precursors results from a signaling cascade that involves the pacemaker activity of HCN channels, the opening of voltage‐gated Ca2+‐channels, activation of Ca2+/calmodulin‐dependent kinase II and phosphorylation of cAMP‐responsive element‐binding protein.
Architecture of a lamellicorn flagellum (Phyllopertha horticola, scarabaeidae, coleoptera, insecta)

The distal three of the seven flagellar segments of the scarabaeid beetle Phyllopertha horticola are lamelliform, gathered into a club, and possess five sensillar fields that are packed with sensilla placodea. The most proximal surface of the club bears only hair‐shaped sensilla. On the inner four sensillar fields a narrow central elongated zone houses pit organs and cavities with sunken sensilla placodea and other sensilla. The most distal, fifth sensillar field is smooth. The sensilla placodea seem to be of several types. The only distinct difference between the sexes is the shorter and more rounded lamellae of the female. The total count of sensilla placodea in males outnumbers that of the females by about 60%.
Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects

The β‐site APP cleaving enzymes 1 and 2 (BACE1 and BACE2) were initially identified as transmembrane aspartyl proteases cleaving the amyloid precursor protein (APP). BACE1 is a major drug target for Alzheimer's disease because BACE1‐mediated cleavage of APP is the first step in the generation of the pathogenic amyloid‐β peptides. BACE1, which is highly expressed in the nervous system, is also required for myelination by cleaving neuregulin 1. Several recent proteomic and in vivo studies using BACE1‐ and BACE2‐deficient mice demonstrate a much wider range of physiological substrates and functions for both proteases within and outside of the nervous system. For BACE1 this includes axon guidance, neurogenesis, muscle spindle formation, and neuronal network functions, whereas BACE2 was shown to be involved in pigmentation and pancreatic β‐cell function. This review highlights the recent progress in understanding cell biology, substrates, and functions of BACE proteases and discusses the therapeutic options and potential mechanism‐based liabilities, in particular for BACE inhibitors in Alzheimer's disease.
SVCT2 transporter expression is post‐natally induced in cortical neurons and its function is regulated by its short isoform

Different studies have demonstrated the importance of micronutrients, such as vitamins, for normal adult brain function and development. Vitamin C is not synthesized in the brain, but high levels are detected in this organ because of the existence of specific uptake mechanisms, which concentrate ascorbic acid from the bloodstream to the cerebrospinal fluid and then into neurons and glial cells. Two different isoforms of sodium–vitamin C cotransporters (SVCT1 and SVCT2) have been cloned. SVCT2 expression has been observed in the adult hippocampus and cortical neurons by in situ hybridization. In addition, the localization of SVCT2 in the rat fetal brain has been studied by immunohistochemistry and in situ hybridization, demonstrating that SVCT2 is highly expressed in the ventricular and subventricular areas of the brain cortex. However, there are currently no immunohistochemical data regarding SVCT2 expression and function in the post‐natal brain. Therefore, we analyzed SVCT2 expression in the developing brain cortex of mice, and demonstrated an increase in SVCT2 mRNA in mice at 1–15 days of age. The expression of a short isoform, SVCT2sh, was also detected within the same period. SVCT2 expression was concentrated in neurons within the inner layer of the brain cortex. Both SVCT2 isoforms were coexpressed in N2a cells to obtain functional data. Fluorescence resonance energy transfer analysis revealed a molecular interaction between SVCT2wt and SVCT2sh. Finally, differences in transport ratios suggested that SVCT2sh expression inhibited ascorbic acid uptake in N2a cells when both isoforms were coexpressed.
Morphological corollaries and ecological implications of flightlessness in the kakapo (Psittaciformes: Strigops habroptilus)

The morphological corollaries of flightlessness of the kakapo (Strigops habroptilus) have been studied using skin specimens, skeletons, and pectoral dissection of an anatomical specimen. These have been compared with the closely related, flighted kea (Nestor notabilis), and secondarily with other Psittaciformes and the convergent hoatzin (Cuculiformes: Opisthocomus hoazin). S. habroptilus is the most massive and sexually dimorphic psittaciform in the world, and has the smallest relative wing size of any parrot. Alar pterylography of S. habroptilus is similar to that of other parrots, but remiges of the species are shorter, comparatively rounded, show less asymmetry of vanes, and have fewer interlocking barbules distally. S. habroptilus shows peculiarities of the sternum (vestigial carina, shortened spina externa), coracoid (elongate processus lateralis, enlarged angle with scapula), and humerus (prominent tuberculum ventrale, undercut crista bicipitalis). Pectoral skeletal dimensions of S. habroptilus are smaller than those of N. notabilis, whereas the reverse is true for pelvic dimensions. Most skeletal dimensions of S. habroptilus are more variable (within sexes) than those of N. notabilis. Proximal wing elements are disproportionately long and distal elements disproportionately short in S. habroptilus. The legs of S. habroptilus are characterized by disproportionately long femora and disproportionately short tarsometatarsi. Distinctive features of the pectoral musculature of S. habroptilus include a greatly reduced Mm. pectoralis thoracica and supracoracoideus, the absence of a distinct proximal muscle belly of M. propatagialis tendo longus, an extensive M. cucullaris capitis clavicularis associated with a voluminous crop, and an essentially tendinous M. sternocoracoideus. Relative to mean body mass, all dimensions of the antebrachial, carpometacarpal, digital, and patagial muscles are smaller in S. habroptilus than in N. notabilis. These aspects are compared to those of other flightless birds. Discussed are implications of flightlessness and associated large body size of S. habroptilus for issues of thermodynamics, metabolism, activity patterns, digestive anatomy, diet, reproduction, and insularit. © 1992 Wiley‐Liss, Inc.
Elevation of striatal urate in experimental models of Parkinson's disease: a compensatory mechanism triggered by dopaminergic nigrostriatal degeneration?

Epidemiological studies have indicated an inverse association between high uricemia and incidence of Parkinson's disease (PD). To investigate the link between endogenous urate and neurotoxic changes involving the dopaminergic nigrostriatal system, this study evaluated the modifications in the striatal urate levels in two models of PD. To this end, a partial dopaminergic degeneration was induced by 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) in mice, while a severe dopaminergic degeneration was elicited by unilateral medial forebrain bundle infusion of 6‐hydroxydopamine (6‐OHDA) in rats. Urate levels were measured by in vivo microdialysis at 7 or 14 days from toxin exposure. The results obtained demonstrated higher urate levels in the dopamine‐denervated striatum of 6‐OHDA‐lesioned rats compared with the intact striatum. Moreover, an inverse correlation between urate and dopamine levels was observed in the same area. In contrast, only a trend to significant increase in striatal urate was observed in MPTP‐treated mice. These results demonstrate that a damage to the dopaminergic nigrostriatal system elevates the striatal levels of urate, and suggest that this could be an endogenous compensatory mechanism to attenuate dopaminergic neurodegeneration. This finding may be important in light of the epidemiological and preclinical evidences that indicate a link between urate and development of PD.
The role of prophylactic anti‐emetic therapy in emergency department patients receiving intravenous morphine for musculoskeletal trauma

Objective: To determine if there is benefit in routine administration of the anti-emetic metoclopramide to patients receiving intravenous morphine for musculoskeletal trauma. Method: A randomized double-blind placebo controlled trial using 214 patients who presented to Dunedin Hospital Emergency Department with musculoskeletal trauma, requiring intravenous morphine for analgesia. Those recruited were randomized to two groups. Group one received placebo prior to morphine while those in group two received metoclopramide 10 mg intravenously, prior to morphine. Any vomiting or severe nausea within 2 h of receiving intravenous morphine was recorded. Results: The two groups were evenly matched for age, sex and morphine dose. Overall, 3.7% of patients in the study vomited (1.9% in the group receiving placebo and 5.4% in the group receiving metoclopramide). This difference was not significant (P = 0.17). The mean age was 78.5 years in the group that did vomit compared with a mean age of 46.0 years in those not vomiting. This difference was highly significant (P = 0.0009). Conclusion: The incidence of vomiting in patients receiving intravenous morphine for musculoskeletal trauma is low and the routine use of an anti-emetic in these patients is not justified. Intravenous metoclopramide in these patients does not reduce the incidence of vomiting.
Robotic-Assisted and Laparoscopic Sacrocolpopexy: Comparing Operative Times, Costs and Outcomes

Objectives: To compare operative times, hospital costs, and surgical outcomes for robotic-assisted laparoscopic sacrocolpopexy (RALSC) and laparoscopic sacrocolpopexy (LSC). Methods: A retrospective cohort study of 104 subjects who underwent RALSC (n = 43) or LSC (n = 61) for vaginal vault prolapse was performed. The primary outcomes were operative time and hospital costs. The secondary outcomes included blood loss, complications, and objective cure rates. &khgr;2 and t tests were used. Results: The mean operative time was longer in RALSC than in LSC (281 ± 58 vs 206 ± 42 minutes; P < 0.001) with setup time accounting for only 9 minutes of this difference. Direct costs (expressed in cost units) for hospital stay were similar (437 ± 88 vs 450 ± 119 units; P = 0.738) while surgical costs remained higher for RALSC (2724 ± 413 vs 2295 ± 342 units; P < 0.01). Blood loss and complications were similar, and objective cure was not significantly different for RALSC vs LSC (90% vs 80%, P = 0.19). Conclusions: Robotic-assisted laparoscopic sacrocolpopexy achieves similar perioperative outcomes compared to LSC with increased surgical time resulting in increased costs.
Cannabinoid receptor 1 modulates the autophagic flux independent of mTOR‐ and BECLIN1‐complex

Cannabinoid Receptor 1 (CB1) has been initially described as the receptor for Delta‐9‐Tetrahydrocannabinol in the central nervous system (CNS), mediating retrograde synaptic signaling of the endocannabinoid system. Beside its expression in various CNS regions, CB1 is ubiquituous in peripheral tissues, where it mediates, among other activities, the cell's energy homeostasis. We sought to examine the role of CB1 in the context of the evolutionarily conserved autophagic machinery, a main constituent of the regulation of the intracellular energy status. Manipulating CB1 by siRNA knockdown in mammalian cells caused an elevated autophagic flux, while the expression of autophagy‐related genes remained unaltered. Pharmacological inhibition of CB1 activity using Rimonabant likewise caused an elevated autophagic flux, which was independent of the mammalian target of rapamycin complex 1, a major switch in the control of canonical autophagy. In addition, knocking down coiled‐coil myosin‐like BCL2‐interacting protein 1, the key‐protein of the second canonical autophagy control complex, was insufficient to reduce the elevated autophagic flux induced by Rimonabant. Interestingly, lysosomal activity is not altered, suggesting a specific effect of CB1 on the regulation of autophagic flux. We conclude that CB1 activity affects the autophagic flux independently of the two major canonic regulation complexes controlling autophagic vesicle formation.
Gender differences between hypocretin/orexin knockout and wild type mice: age, body weight, body composition, metabolic markers, leptin and insulin resistance

Female hypocretin knockout (Hcrt KO) mice have increased body weight despite decreased food intake compared to wild type (WT) mice. In order to understand the nature of the increased body weight, we carried out a detailed study of Hcrt KO and WT, male, and female mice. Female KO mice showed consistently higher body weight than WT mice, from 4 to 20 months (20–60%). Fat, muscle, and free fluid levels were all significantly higher in adult (7–9 months) as well as old (18–20 months) female KO mice compared to age‐matched WT mice. Old male KO mice showed significantly higher fat content (150%) compared to age‐matched WT mice, but no significant change in body weight. Respiratory quotient (−19%) and metabolic rates (−14%) were significantly lower in KO mice compared to WT mice, regardless of gender or age. Female KO mice had significantly higher serum leptin levels (191%) than WT mice at 18–20 months, but no difference between male mice were observed. Conversely, insulin resistance was significantly higher in both male (73%) and female (93%) KO mice compared to age‐ and sex‐matched WT mice. We conclude that absence of the Hcrt peptide has gender‐specific effects. In contrast, Hcrt‐ataxin mice and human narcoleptics, with loss of the whole Hcrt cell, show weight gain in both sexes.