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Phototransduction in Drosophila is mediated by phospholipase C (PLC) and Ca2+-permeable TRP channels, but the function of endoplasmic reticulum (ER) Ca2+ stores in this important model for Ca2+ signaling remains obscure. We therefore expressed a low affinity Ca2+ indicator (ER-GCaMP6-150) in the ER, and measured its fluorescence both in dissociated ommatidia and in vivo from intact flies of both sexes. Blue excitation light induced a rapid (tau ∼0.8 s), PLC-dependent decrease in fluorescence, representing depletion of ER Ca2+ stores, followed by a slower decay, typically reaching ∼50% of initial dark-adapted levels, with significant depletion occurring under natural levels of illumination. The ER stores refilled in the dark within 100-200 s. Both rapid and slow store depletion were largely unaffected in InsP3 receptor mutants, but were much reduced in trp mutants. Strikingly, rapid (but not slow) depletion of ER stores was blocked by removing external Na+ and in mutants of the Na+/Ca2+ exchanger, CalX, which we immuno-localized to ER membranes in addition to its established localization in the plasma membrane. Conversely, overexpression of calx greatly enhanced rapid depletion. These results indicate that rapid store depletion is mediated by Na+/Ca2+ exchange across the ER membrane induced by Na+ influx via the light-sensitive channels. Although too slow to be involved in channel activation, this Na+/Ca2+ exchange-dependent release explains the decades-old observation of a light-induced rise in cytosolic Ca2+ in photoreceptors exposed to Ca2+-free solutions.SIGNIFICANCE STATEMENT Phototransduction in Drosophila is mediated by phospholipase C, which activates TRP cation channels by an unknown mechanism. Despite much speculation, it is unknown whether endoplasmic reticulum (ER) Ca2+ stores play any role. We therefore engineered flies expressing a genetically encoded Ca2+ indicator in the photoreceptor ER. Although NCX Na+/Ca2+ exchangers are classically believed to operate only at the plasma membrane, we demonstrate a rapid light-induced depletion of ER Ca2+ stores mediated by Na+/Ca2+ exchange across the ER membrane. This NCX-dependent release was too slow to be involved in channel activation, but explains the decades-old observation of a light-induced rise in cytosolic Ca2+ in photoreceptors bathed in Ca2+-free solutions.

Phototransduction in Drosophila is mediated by phospholipase C (PLC) and Ca2+-permeable TRP channels, but the function of endoplasmic reticulum (ER) Ca2+ stores in this important model for Ca2+ signaling remains obscure. We therefore expressed a low affinity Ca2+ indicator (ER-GCaMP6-150) in the ER, and measured its fluorescence both in dissociated ommatidia and in vivo from intact flies of both sexes. Blue excitation light induced a rapid (tau ~0.8 s), PLC-dependent decrease in fluorescence, representing depletion of ER Ca2+ stores, followed by a slower decay, typically reaching ~50% of initial dark-adapted levels, with significant depletion occurring under natural levels of illumination. The ER stores refilled in the dark within 100-200 s. Both rapid and slow store depletion were largely unaffected in InsP3 receptor mutants, but were much reduced in trp mutants. Strikingly, rapid (but not slow) depletion of ER stores was blocked by removing external Na+ and in mutants of the Na+/Ca2+ exchanger, CaIX, which we immuno-localized to ER membranes in addition to its established localization in the plasma membrane. Conversely, overexpression of calx greatly enhanced rapid depletion. These results indicate that rapid store depletion is mediated by Na+/Ca2+ exchange across the ER membrane induced by Na+ influx via the light-sensitive channels. Although too slow to be involved in channel activation, this Na+/Ca2+ exchange-dependent release explains the decades-old observation of a light-induced rise in cytosolic Ca2+ in photoreceptors exposed to Ca2+-free solutions. [ABSTRACT FROM AUTHOR]

Background: Metal-on-metal total hip replacements (THRs) with large femoral heads have been associated with elevated levels of cobalt (Co) and chromium (Cr), which have been attributed to high levels of wear at the articular surface. Our unit recently published data showing a significant increase in the mean levels of Co ions in patients with a 36-mm diameter femoral head with the metal-on-polyethylene Trident-Accolade system. The aim of this study is to assess the levels of Co and Cr in the Exeter-Trident hybrid system, as similar findings would raise concern over the V40 taper trunnion.Materials and Methods: The study included 83 patients (45 male and 38 female with a mean age of 75.6 years) who received Exeter-Trident hybrid metal-on-polyethylene THRs. The patients were then divided into two groups according to the diameter of the femoral head used-38 patients in the 28-mm group (control), and 45 in the 36-mm (experimental) group. Serum levels of blood Co and Cr were analysed for all recruited patients.Results: In the control group (28-mm femoral head) all Co and Cr values were normal (under the abnormal threshold), as were the experimental group (36-mm femoral head). The data values were below <10 nmol and <40 nmol for Co and Cr, respectively.Conclusion: Since the National Joint Registry (NJR) states that the Exeter femoral stem is the commonest cemented femoral stem prosthesis used in the UK, we found it imperative that these results are documented given the corresponding findings in the Trident-Accolade system in our previous study. This study provides relative reassurance that the issue does not lie with the V40 taper trunnion, but raises suspicion that the issue may be with the titanium Accolade stem with large diameter femoral heads. [ABSTRACT FROM AUTHOR]

Introduction: Recent controversies surrounding metal-on-metal (MoM) hip resurfacing has led to a substantial decline in its use. Despite this, there is good evidence to support the use of specific implants in select patients. Patients and methods: A retrospective analysis of Birmingham Hip Resurfacing (BHR) patients with a minimum of 10 years follow-up was performed. Functional scoring was performed with the Oxford Hip Score (OHS) and failure was defined as revision for any cause. 111 patients underwent 121 BHR procedures. All patients had a minimum follow-up of 10 years. 70 patients (63%) were male. Mean patient age at surgery was 52.5 years (male 53.9 years, female 48.8 years). Results: Overall survival at 10 years was 91% (97% male, 80% female). There was a statistically significant improvement in OHS postoperatively which remains at 10-year follow-up (p = <0.05). There was no significant difference in scores between the male and female groups. Revisions were most often in patients with smaller component sizes but this was not found to be statistically significant. Conclusions: Our results reflect that of the wider literature in that good outcomes can be obtained with this implant in a select group of patients and results are comparable to that of conventional hip arthroplasty in patients of a similar age. [ABSTRACT FROM AUTHOR]

Phototransduction in Drosophila is mediated by phospholipase C (PLC) and Ca 2+ -permeable TRP channels, but the function of endoplasmic reticulum (ER) Ca 2+ stores in this important model for Ca 2+ signaling remains obscure. We therefore expressed a low affinity Ca 2+ indicator (ER-GCaMP6-150) in the ER, and measured its fluorescence both in dissociated ommatidia and in vivo from intact flies of both sexes. Blue excitation light induced a rapid (tau ∼0.8 s), PLC-dependent decrease in fluorescence, representing depletion of ER Ca 2+ stores, followed by a slower decay, typically reaching ∼50% of initial dark-adapted levels, with significant depletion occurring under natural levels of illumination. The ER stores refilled in the dark within 100-200 s. Both rapid and slow store depletion were largely unaffected in InsP 3 receptor mutants, but were much reduced in trp mutants. Strikingly, rapid (but not slow) depletion of ER stores was blocked by removing external Na + and in mutants of the Na + /Ca 2+ exchanger, CalX, which we immuno-localized to ER membranes in addition to its established localization in the plasma membrane. Conversely, overexpression of calx greatly enhanced rapid depletion. These results indicate that rapid store depletion is mediated by Na + /Ca 2+ exchange across the ER membrane induced by Na + influx via the light-sensitive channels. Although too slow to be involved in channel activation, this Na + /Ca 2+ exchange-dependent release explains the decades-old observation of a light-induced rise in cytosolic Ca 2+ in photoreceptors exposed to Ca 2+ -free solutions. SIGNIFICANCE STATEMENT Phototransduction in Drosophila is mediated by phospholipase C, which activates TRP cation channels by an unknown mechanism. Despite much speculation, it is unknown whether endoplasmic reticulum (ER) Ca 2+ stores play any role. We therefore engineered flies expressing a genetically encoded Ca 2+ indicator in the photoreceptor ER. Although NCX Na + /Ca 2+ exchangers are classically believed to operate only at the plasma membrane, we demonstrate a rapid light-induced depletion of ER Ca 2+ stores mediated by Na + /Ca 2+ exchange across the ER membrane. This NCX-dependent release was too slow to be involved in channel activation, but explains the decades-old observation of a light-induced rise in cytosolic Ca 2+ in photoreceptors bathed in Ca 2+ -free solutions., (Copyright © 2020 the authors.)