Miracle-dz/UniFAR-FTUs huggingface dataset:
Nitric oxide signaling is disrupted in the yeast model for Batten disease.

The juvenile form of neuronal ceroid lipofuscinoses (JNCLs), or Batten disease, results from mutations in the CLN3 gene, and it is characterized by the accumulation of lipopigments in the lysosomes of several cell types and by extensive neuronal death. We report that the yeast model for JNCL (btn1-Delta) that lacks BTN1, the homologue to human CLN3, has increased resistance to menadione-generated oxidative stress. Expression of human CLN3 complemented the btn1-Delta phenotype, and equivalent Btn1p/Cln3 mutations correlated with JNCL severity. We show that the previously reported decreased levels of L-arginine in btn1-Delta limit the synthesis of nitric oxide (.NO) in both physiological and oxidative stress conditions. This defect in . NO synthesis seems to suppress the signaling required for yeast menadione-induced apoptosis, thus explaining btn1-Delta phenotype of increased resistance. We propose that in JNCL, a limited capacity to synthesize . NO directly caused by the absence of Cln3 function may contribute to the pathology of the disease.
Acupuncture for Chronic Low Back Pain in Routine Care: A Multicenter Observational Study

ObjectiveTo investigate patient characteristics and outcomes after undergoing acupuncture treatment for chronic low back pain (cLBP) in Germany and to analyze chronification, pain grading, and depression as predictors for treatment outcomes. Patients and MethodsPatients with cLBP (ICD-10 diagnoses M54.4 or M54.5) who underwent acupuncture therapy (mean number of sessions 8.7±2.9) within the framework of a reimbursement and research program sponsored by German statutory sickness funds were included in an observational study. Patients were asked to complete detailed questionnaires that included questions on intensity and frequency of pain and instruments measuring functional ability, depression, and quality of life (SF-36) before and after treatment and 6 months after beginning acupuncture. Participating physicians assessed pain chronification in patients. ResultsA total of 2564 patients (mean age 57.7±14.0 y, 78.7% female), who were treated by 1607 physicians, were included in the main analysis. After 6 months (6-mo follow-up), 45.5% of patients demonstrated clinically significant improvements in their functional ability scores. The mean number of days with pain was decreased by half (from 21 to 10 d/mo). Employed patients (employed patient subgroup analysis) reported a 30% decrease from baseline in days of work lost. In all, 8.1% of patients reported adverse events, the majority of which were minor. Subgroup analyses focusing on pain severity, stage of chronification, and depression revealed statistically significant relationships both to baseline measures and to reduction of pain after acupuncture. ConclusionsAcupuncture treatment is associated with clinically relevant improvements in patients suffering from cLBP of varying degrees of chronification and/or severity.
Validity, prognostic value and optimal cutoff of respiratory muscle strength in patients with chronic heart failure changes with beta-blocker treatment

Background Training studies frequently use maximum inspiratory mouth occlusion pressure (PImax) as a therapeutic target and surrogate marker. For patients on β-blocker (BBL), prognostic data allowing this extrapolation do not exist. Furthermore, the effects of BBL, mainstay of modern chronic heart failure therapy, on respiratory muscle function remain controversial. Finally, no proper separate cutoff according to treatment exists. Design Prospective, observational inclusion of patients with stable systolic chronic heart failure and recording of 1 year and all-time mortality for endpoint analysis. Methods In 686 patients, 81% men, 494 patients on BBL, PImax was measured along with clinical evaluation. The median follow-up was 50 months (interquartile range: 26–75 months). Results Patients with or without BBL did not differ significantly for PImax, percentage of predicted PImax or other marker of disease severity. PImax was a significant (hazard ratio: 0.925; 95% confidence interval: 0.879–0.975; χ2: 8.62) marker of adverse outcome, independent of BBL-status or aetiology. Percentage of predicted PImax was not independent of PImax. The cutoff identified through receiver-operated characteristics for 1-year mortality was 4.14 kPa for patients on BBL and 7.29 kPa for patients not on BBL. When separated accordingly, 1-year mortality was 8.5 versus 21.4%, P = 0.02, for patients not on BBL and 4.3 versus 16.2%, P < 0.001, for patients on BBL. Conclusion This study fills the gap between trials targeting respiratory muscle on a functional basis and the resultant prognostic information with regard to BBL. BBL lowered the optimal PImax cutoff values for risk stratification without changing the measured values of PImax. This should be considered at inclusion and evaluation of trials and interpretation of exercise parameters.
Tenascin‐R inhibits regrowth of optic fibers in vitro and persists in the optic nerve of mice after injury

Tenascin‐R, an extracellular matrix constituent expressed by oligodendrocytes and some neuronal cell types, may contribute to the inhibition of axonal regeneration in the adult central nervous system. Here we show that outgrowth of embryonic and adult retinal ganglion cell axons from mouse retinal explants is significantly reduced on homogeneous substrates of tenascin‐R or a bacterially expressed tenascin‐R fragment comprising the epidermal growth factor‐like repeats (EGF‐L). When both molecules are presented as a sharp substrate border, regrowing adult axons do not cross into the tenascin‐R or EGF‐L containing territory. All in vitro experiments were done in the presence of laminin, which strongly promotes growth of embryonic and adult retinal axons, suggesting that tenascin‐R and EGF‐L actively inhibit axonal growth. Contrary to the disappearance of tenascin‐R from the regenerating optic nerve of salamanders (Becker et al., J Neurosci 19:813–827, 1999), the molecule remains present in the lesioned optic nerve of adult mice at levels similar to those in unlesioned control nerves for at least 63 days post‐lesion (the latest time point investigated), as shown by immunoblot analysis and immunohistochemistry. In situ hybridization analysis revealed an increase in the number of cells expressing tenascin‐R mRNA in the lesioned nerve. We conclude that, regardless of the developmental stage, growth of retinal ganglion cell axons is inhibited by tenascin‐R and we suggest that the continued expression of the protein after an optic nerve crush may contribute to the failure of adult retinal ganglion cells to regenerate their axons in vivo. GLIA 29:330–346, 2000. © 2000 Wiley‐Liss, Inc.
Activation of Src family kinases by colony stimulating factor‐1, and their association with its receptor.

The receptor for the macrophage colony stimulating factor‐1 (CSF‐1R) is a transmembrane glycoprotein with intrinsic tyrosine kinase activity. CSF‐1 stimulation promotes the growth of cells of the macrophage lineage and of fibroblasts engineered to express CSF‐1R. We show that CSF‐1 stimulation resulted in activation of three Src family kinases, Src, Fyn and Yes. Concomitant with their activation, all three Src family kinases were found to associate with the ligand‐activated CSF‐1 receptor. These interactions were also demonstrated in SF9 insect cells co‐infected with viruses encoding the CSF‐1 receptor and Fyn, and the isolated SH2 domain of Fyn was capable of binding the CSF‐1R in vitro. Analysis of mutant CSF‐1Rs revealed that the ‘kinase insert’ (KI) domain of CSF‐1R was not required for interactions with Src family kinases, but that mutation of one of the receptor autophosphorylation sites, Tyr809, reduced both their binding and enzymatic activation. Because fibroblasts expressing this receptor mutant are unable to form colonies in semi‐solid medium or to grow in chemically defined medium in the presence of CSF‐1, the Src family kinases may play a physiological role in the mitogenic response to CSF‐1.
Transabdominal Saline Contrast Sonohysterography : Can It Replace Hysterosalpingography In Low Resource Countries ?

Conclusion: The readily available, easy to interpret TASCSH is not only safer and cheaper but it’s as accurate as HSG in evaluating the fallopian tubes and uterine cavity in infertile patients. We advocate its use as replacement for HSG in environment like ours where Hysteroscopy, MRI, positive contrast sonohysterography, transvaginal probes and skill are not readily available. AdemolA A. Aremu, Victor A. Adetiloye, BolAnle o. iBitoye, dAniel A. AdeKAnle, tope o.Bello r ad io lo g y S ec tio n
A novel 5-HT1-like receptor subtype mediates cAMP synthesis in porcine pial vein.

The 5-hydroxytryptamine (5-HT) receptor subtype mediating 5-HT inhibition of spontaneous rhythmic contractions (SRC) in the porcine pial vein was characterized. Results from pharmacological studies using in vitro tissue bath techniques indicated that the inhibitory effects of 5-HT on SRC were qualitatively and quantitatively mimicked by 5-HT1-like agonists 5-methoxytryptamine (5-MT) and 5-carboxamidotryptamine (5-CT). 5-HT-, 5-MT-, and 5-CT-induced inhibitions of SRC were attenuated in a concentration-dependent manner by methysergide, which yielded similar pA2 values against these three agonists, suggesting that 5-HT, 5-MT, and 5-CT act on the same 5-HT1-like receptors. 5-MT inhibition of SRC was not affected by blocking 5-HT2 (with ketanserin and spiperone), 5-HT3 (with MDL-72222 and ICS-205-930), or 5-HT4 (with ICS-205-930) receptors. Neither was 5-MT inhibition of SRC affected by blocking 5-HT1A (with propranolol and spiperone), 5-HT1B (with propranolol), or 5-HT1C (with ketanserin) receptors. Furthermore, 5-HT and 5-MT inhibitions of SRC were enhanced by cilostazol [a selective adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase inhibitor] and were diminished by KT-5720 (a cAMP-dependent protein kinase inhibitor) but were not affected by M&B-22948 [a selective guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor] or KT-5823 (a cGMP-dependent protein kinase inhibitor). Biochemical studies further demonstrated that 5-HT inhibition of SRC in porcine pial veins was accompanied by an increase in cAMP, but not cGMP, synthesis. (ABSTRACT TRUNCATED AT 250 WORDS)
Epidemiology of Motor Vehicle Crashes in Utah

Objectives: This study describes the frequency and pattern of vehicle crashes and safety belt use in Utah; the proportion of vehicle crashes involving safety belt use, alcohol, and fatigue; and the influence these factors and others have on emergency room visits or hospital admissions and on the severity of the outcome. Methods: Data were obtained from the Utah Department of Transportation, Division of Traffic and Safety, from 1999 through 2005. Motor vehicle crash (MVC) data were linked to statewide hospital admission (inpatient) and emergency department (ED) records. Results: The trend in rates of crashes significantly decreased for both males and females, with rates of crashes involving alcohol decreasing for males but increasing for females and rates of crashes involving fatigue remaining constant for males and females over the study period. Drivers not wearing a safety belt or intoxicated or fatigued were significantly more likely to have contributed to the crash, visit the emergency room, be admitted to the hospital, and experience severe injury or death. Drivers in crashes who were intoxicated or fatigued were significantly less likely to be wearing a safety belt. When a safety belt was worn at the time of the crash, sitting in the front seat was safer than in the second or third seats, and sitting on the left side of the vehicle was safer than on the right side or in the middle. However, when a safety belt was not worn at the time of the crash, sitting in the front seat was more likely associated with injury or death than in the second or third seats or sitting in the middle seat. Conclusion: Drivers in crashes who were intoxicated or fatigued were less likely to be wearing a safety belt and more likely to have contributed to the crash and experience serious injury or death. Severity of injury related to seat placement is moderated by safety belt use.
Vestibular Deterioration Precedes Hearing Deterioration in the P51S COCH Mutation (DFNA9): An Analysis in 74 Mutation Carriers

Objectives: To analyze cochleovestibular impairment features in P51S COCH mutation carriers (n = 22) in a new, large Dutch family and to compare the results to those obtained in previously identified similar mutation carriers (n = 52). To evaluate age-related features between progressive hearing and vestibular impairment of all mutation carriers (n = 74). Study Design: Family study. Methods: Regression analysis was performed in relation to age to outline the development of hearing thresholds, speech recognition scores, and vestibulo-ocular reflex time constant as the key vestibular response parameter. Results: Pure tone thresholds, phoneme recognition scores, and vestibular responses of the mutation carriers in the new family were essentially similar to those previously established in all other mutation carriers. Hearing started to deteriorate in all mutation carriers from 43 years of age onwards, whereas deterioration of vestibular function started from age 34. Conclusion: Vestibular impairment starts earlier, progresses more rapidly, and, eventually, is more complete than hearing impairment in P51S COCH mutation carriers.
The Ca2+/Mn2+-transporting SPCA2 pump is regulated by oxygen and cell density in colon cancer cells.

The mammalian SPCA1 and SPCA2 ATPases localize in membranes of the secretory pathway and transport ions of Ca(2+) and Mn(2+) The role of tissue-specific SPCA2 isoform, highly expressed in lungs, mammary gland and gastrointestinal tract, is poorly understood. To elucidate the function of SPCA2, we studied human colon cancer HCT116 cells, grown under ambient and decreased O2 levels. We found that in contrast with other Ca(2+)-ATPase isoforms the expression of SPCA2 was up-regulated under hypoxia (3% O2), in both adherent (2D) and spheroid (3D) cultures. In spheroids, experiencing lowest O2 levels (30-50 μM, measured by phosphorescence lifetime imaging microscopy), we observed lower staining with reactive oxygen species (ROS)-specific fluorescent probe, which correlated with increased SPCA2. However, SPCA2 expression was up-regulated in cells exposed to reactive oxygen and nitrogen species donors, and when grown at higher density. We noticed that the culture exposed to hypoxia showed overall increase in S phase-positive cells and hypothesized that SPCA2 up-regulation under hypoxia can be linked to Mn(2+)-dependent cell cycle arrest. Consequently, we found that SPCA2-transfected cells display a higher number of cells entering S phase. Altogether, our results point at the important role of SPCA2 in regulation of cell cycle in cancer cells.
Endoscopic Transventricular Approach to Third Ventricular Colloid Cyst

© 2015 Egyptian Journal of Neurosurgery. All rights reserved Background: Colloid cysts typically presents with manifestations of increased intracranial pressure due to association with obstructive hydrocephalus. Many management options exist including expectant observation, ventriculo-peritoneal (v/p) shunt, microsurgical resection and endoscopic transventricular cyst excision. Endoscopic approach brings together the value of resection and the avoidance of complications of open techniques. Objective: Assessment of the efficacy and safety of endoscopic approach to colloid cysts. Patients and Methods: Twelve cases of colloid cysts were operated upon by endoscopic technique using the uniportal approach in the period between 2004 and 2015. Results: Seven females and five males were included. Headache was the most common symptom followed by memory disturbance. Total resection was achieved in 50% of the endoscopic cases. In one case we had to shift to microsurgery due to hard contents. One case had symptomatic recurrence requiring surgery. Temporary postoperative memory affection occurred in four cases (30%). Four patients (30%) needed postoperative V/P shunt. Conclusion: Endoscopic approach to colloid cyst is safe, effective and with relative low morbidity.
Consumer attitudes for new plant species using the example of Trachycarpus wagnerianus

This articles reviews the purchase behaviour of consumers for plants and the attitude towards horticultural novelties. The palm, Trachycarpus wagnerianus especially, is the main focus of this study. Based on a survey of 408 customers in Bavaria during autumn 2009, the results gave an impression of how consumers inform themselves about novelties in horticulture as well as their attitude to T. wagnerianus. Within the standardized questionnaire, a conjoint measurement was applied in order to investigate the impact of the different characteristics of the palm on consumers' choice. Drawing all factors of the conjoint measurement into consideration, the T. wagnerianus has slight advantages when compared to the common Trachycarpus fortunei.
Infrequent mutation of the WT1 gene in 77 Wilms' tumors

Homozygous deletions in Wilms' tumor DNA have been a key step in the identification and isolation of the WT1 gene. Several additional loci are also postulated to contribute to Wilms' tumor formation. To assess the frequency of WT1 alterations we have analyzed the WT1 locus in a panel of 77 Wilms' tumors. Eight tumors showed evidence for large deletions of several hundred or thousand kilobasepairs of DNA, some of which were also cytogenetically detected. Additional intragenic mutations were detected using more sensitive SSCP analyses to scan all 10 WTl exons. Most of these result in premature stop codons or missense mutations that inactivate the remaining WTl allele. The overall frequency of WTl alterations detected with these methods is less than 15%. While some mutations may not be detectable with the methods employed, our results suggest that direct alterations of the WTl gene are present in only a small fraction of Wilms' tumors. Thus, mutations at other Wilms' tumor loci or disturbance of interactions between these genes likely play an important role in Wilms' tumor development. © 1994 Wiley‐Liss, Inc.
Effect of sensory stimulation in rat barrel cortex, dorsolateral striatum and on corticostriatal functional connectivity

The striatum integrates sensory information to enable action selection and behavioural reinforcement. In the rat, a large topographical projection from the rat barrel cortex to widely distributed areas of the striatum is assumed to be an important structural component supporting these processes. The striatal sensory response is, however, not comprehensively understood at a network level. We used a 10‐Hz, 100‐ms air puff, allowing undamped movement of multiple whiskers, to look at functional connectivity in contralateral cortex and striatum in response to sensory stimulation. Simultaneous recordings of cortical and striatal local field potentials (LFPs) were made under isoflurane anaesthesia in 15 male Brown Norway rats. Four electrodes were placed in the barrel cortex while the dorsolateral striatum was mapped with a 500‐μm resolution, resulting in a maximum of 315 recording positions per animal. Significant event‐related responses were unevenly distributed throughout the striatum in 34.8% of positions recorded within this area. Only 10.3% of recorded positions displayed significant total power increases in the LFPs during the stimulation period at the stimulus frequency. This suggests that the responses seen in the LFPs are due to phase rearrangement rather than an amplitude increase in the signal. Analysis of corticostriatal imaginary coherence revealed stimulus‐induced changes in the functional connectivity of 12% of corticostriatal pairs, the sensory response of sparsely distributed neuronal ensembles within the dorsolateral striatum is reflected in the phase relationship between the cortical and striatal local fields.
Measurement of correlation of partition coefficients of polar amino acids.

The distribution coefficients of 12 commonly occurring amino acids were measured with high precision by a radiometric method. Values obtained for the logarithm of the ratio of distribution between octanol and 10 mM phosphate buffer, pH 7.0, are as follows: tryptophan, -1.11; histidine, -1.95; valine, -2.26; proline, -2.54; 3-carboxypiperidine, -2.66; alanine, -2.74; threonine, -2.94; serine, -3.07; γ-aminobutyric acid, -3.17; lysine, -3.05; glutamic acid, -3.69; and arginine, -4.08. Preliminary studies at other pH values show that, at pH 7, the charged amino acids partition into the octanol phase in their charged form. These and literature results can be reconciled with partition coefficient additivity rules most easily by assuming that (a) structural changes affect amino acid partitioning by only 0.6 of their effect on more lipophilic molecules, and (b) in octanol the NH3+ and COO- moieties "self-solvate" polar side-chains as well as each other. The experimental values for the partition coefficients correlate moderately well with the hydrophobicity scale of Nozaki and Tanford [ J. Biol. Chem. 246 :2211-2217 (1971)]. ACKNOWLEDGMENT We thank Dr. W. Bondinell for a valuable experimental suggestion.
SMOKING DURING PREGNANCY AND ITS EFFECTS ON THE FETUS

The smoking habits of a group of pregnant women have been recorded and related to the level of carboxyhaemoglobin (COHb) in the circulating blood. Simultaneous maternal and fetal COHb levels at delivery were estimated and on average the fetal levels were 1.8 times greater than the related maternal level. Samples of fetal blood were exposed to carbon monoxide in vitro and an appreciable shift to the left of the haemoglobin dissociation curve was demonstrated. Cigarette smoking during pregnancy diminishes the oxygen carrying capacity of both fetal and maternal blood, affects maternal oxygenation by increased pulmonary venous admixture and diminishes the oxygen available to the fetus at the tissue level by its effect on fetal oxyhaemoglobin dissociation.
NEURON DEGENERATION INDUCED BY VERAPAMIL AND ATTENUATED BY EGb761

Calcium channel blockers are used as neuroprotective agents, as glutamate antagonists. However, it has been found that calcium channel blockers may compromise neuronal survival after long-term exposure. To explore the mechanisms of the toxicity of calcium channel blockers on neurons, we studied the morphological characteristics and biochemical changes of cultured cortical neurons treated with verapamil, a calcium channel blocker. We now report that cerebral cortical cultures exposed to verapamil for 48 h undergo neuronal degeneration in both concentration-dependent and time-dependent fashion, possibly partially through the activation of apoptosis. On the other hand, it was found that Ginkgo biloba extract (EGb761) attenuated verapamil-induced neuronal injury, suggesting the possibility of using verapamil combined with EGb761 clinically. Furthermore, both B-50 immunoactivity (BIA) and the concentration of intracellular calcium in single neurons ([Ca2+]i) decreased after a 48-h exposure to verapamil, suggesting that the mechanisms of verapamil-induced degeneration may be associated with the disruption of intracellular calcium homeostasis and the inhibition of normal axonal elongation.