Landslide assessment through integrated geoelectrical and seismic methods: A case study in Thungsong site, southern Thailand.

Many landslides can cause significant damage to infrastructure, property, and human life. To study landslide structure and processes, geophysical techniques are most productive when employed in combination with other survey and monitoring tools, such as intrusive sampling. Here, the integration of electrical resistivity tomography (ERT) and seismic refraction tomography (SRT) methods is used to assess landslides in Thungsong district, Nakhon Si Thammarat, the south of Thailand, where is a hilly and seasons of prolonged rainfall region. The 2D cross-plot analysis of P-wave velocity and resistivity values obtained by these two methods is introduced to identify potential landslide-prone zones in this region. The results of the 2D cross-plot model reveal detailed image of the subsurface conditions, highlighting areas of low P-wave velocity (lower than 600 m/s) and low resistivity (lower than 600 Ωm). These areas are indicative of weak zone and are potential to be sliding materials. Moreover, an intrusive sampling data from boreholes is also used for the calibration and validation geophysical data with geological data. This can improve the accuracy of landslide assessment and develop effective mitigation strategies to reduce the risk of landslides in this area. In addition of the 2D cross-plot, the volume of sliding material is also determined from the difference of the surface and slipping plane elevations. The volume calculation of sliding material is roughly 33447.76 m3. This approach provides a preliminary tool for landslide studies and monitoring landslides in this region, thus enabling an improved understanding of slope failure processes in this context, and the basis of a landslide mitigation strategy in the future.

Sediment structure at the equatorial mid-atlantic ridge constrained by seafloor admittance using data from the PI-LAB experiment.

Well-constrained marine sediment characteristics (sediment thickness and shear wave velocity) are important not only for the study of climate over geologic times scales but also for correcting and accounting for its presence in seismic data used to investigate deeper structures. We use data from the PI-LAB (Passive Imaging of the Lithosphere Asthenosphere Boundary) experiment, which consisted of 39 broadband ocean bottom seismometers deployed at the Equatorial Mid-Atlantic Ridge near the Chain fracture zone covering 0-80 Myr old seafloor. We compute admittance between the pressure to the vertical displacement at the seafloor at frequencies between 0.1 and 0.2 Hz for microseism-generated Rayleigh waves for 18 stations where data quality is good to determine the sediment thickness and shear wave velocity. We find a general trend of increasing sediment thickness with the seafloor ages, as expected with sediment thicknesses that range from 10-450 m and, shear wave velocities that range from 0.05-0.34 km/s. We find sediment thickness varies almost uniformly across both sides of the ridge, and it indicates that both sides experienced a similar sedimentation process. Our results are in good agreement with the global sediment model that is based on drilling cores and active source experiments, but thinner by up to 50 m at several stations on seafloor older than 25 My. Overlap of the 95% confidence regions between admittance and Ps estimates for thickness and shear velocity is found at 15 stations where we have both Ps and admittance estimates. It suggests that both methods yield accurate estimates for sediment thickness. In addition, our admittance result extends the lateral resolution of sediment characteristics to stations that were not previously resolved by Ps.

Sediment Characterization at the Equatorial Mid-Atlantic Ridge From P-to-S Teleseismic Phase Conversions Recorded on the PI-LAB Experiment.

Accurate marine sediment characteristics, for example, thickness and seismic velocity, are important for constraining sedimentation rates with implications for climate variations and for seismic imaging of deeper structures using ocean bottom seismic deployments. We analyze P-to-S seismic phase conversions from the sediment-crust boundary recorded by the Passive Imaging of the Lithosphere-Asthenosphere Boundary (PI-LAB) experiment to infer the sediment thickness across the Mid-Atlantic Ridge covering 0- to 80-Myr-old seafloor. We find P d s-P delay times of 0.04-0.37 s, or 5- to 82-m thickness. Sediment thickness increases with age. Thickness agrees with global estimates for young (<15-20 Myr) seafloor but is thinner on older lithosphere. Our result may represent a lower limit on sediment thickness, given that several of our stations are on topographic highs. The sedimentation rate decrease observed from 5 to 1.2 mm/kyr at ∼10 Myr suggests a recent increase in productivity related to climate change, eolian dust fluxes, and/or biogenic marine activity.

Mapping the evolving strain field during continental breakup from crustal anisotropy in the Afar Depression.

Rifting of the continents leading to plate rupture occurs by a combination of mechanical deformation and magma intrusion, yet the spatial and temporal scales over which these alternate mechanisms localize extensional strain remain controversial. Here we quantify anisotropy of the upper crust across the volcanically active Afar Triple Junction using shear-wave splitting from local earthquakes to evaluate the distribution and orientation of strain in a region of continental breakup. The pattern of S-wave splitting in Afar is best explained by anisotropy from deformation-related structures, with the dramatic change in splitting parameters into the rift axis from the increased density of dyke-induced faulting combined with a contribution from oriented melt pockets near volcanic centres. The lack of rift-perpendicular anisotropy in the lithosphere, and corroborating geoscientific evidence of extension dominated by dyking, provide strong evidence that magma intrusion achieves the majority of plate opening in this zone of incipient plate rupture.

Magma-assisted rifting in Ethiopia.

The rifting of continents and evolution of ocean basins is a fundamental component of plate tectonics, yet the process of continental break-up remains controversial. Plate driving forces have been estimated to be as much as an order of magnitude smaller than those required to rupture thick continental lithosphere. However, Buck has proposed that lithospheric heating by mantle upwelling and related magma production could promote lithospheric rupture at much lower stresses. Such models of mechanical versus magma-assisted extension can be tested, because they predict different temporal and spatial patterns of crustal and upper-mantle structure. Changes in plate deformation produce strain-enhanced crystal alignment and increased melt production within the upper mantle, both of which can cause seismic anisotropy. The Northern Ethiopian Rift is an ideal place to test break-up models because it formed in cratonic lithosphere with minor far-field plate stresses. Here we present evidence of seismic anisotropy in the upper mantle of this rift zone using observations of shear-wave splitting. Our observations, together with recent geological data, indicate a strong component of melt-induced anisotropy with only minor crustal stretching, supporting the magma-assisted rifting model in this area of initially cold, thick continental lithosphere.

The safety and effectiveness of minor injuries telemedicine.

OBJECTIVES: To determine the safety of minor injuries telemedicine compared with on-site specialist care, current practice, and a robust gold standard, and to assess the clinical effectiveness of this new technique. METHODS: Patients presenting to a peripheral hospital within 10 days of injury were separately assessed by each of: an emergency medicine specialist based at a district general hospital using telemedicine, a second on-site emergency medicine specialist, and an on-site general practitioner (representing current practice). The primary outcome measure was discrepancies between these three medical assessments and a gold standard. All patients were subsequently randomised to follow one of the independent treatment plans generated by the above assessments. Secondary outcomes were recovery and further use of healthcare services measured seven days after recruitment, and consultation duration. RESULTS: 600 patients were recruited over a 12 month period. Overall, 73 discrepancies were identified, with 12 important over-treatments and 11 important under-treatments. No consultation modality was clearly superior to any other, and there were no statistically significant differences in the secondary outcomes of clinical effectiveness measured at seven days. The mean duration of a telemedicine consultation (6.0 min) was almost twice as long as an on-site specialist (3.1 min) or on-site general practitioner consultation (3.4 min) (p<0.0001 in both cases). CONCLUSIONS: Minor injuries telemedicine is safe and clinically effective, providing care that is equivalent to specialist on-site assessment and the current practice of treatment by a general practitioner. There is no evidence that telemedicine provides superior care, and there are a number of process issues that may impede successful implementation of this new technique.

Sedation for children requiring wound repair: a randomised controlled double blind comparison of oral midazolam and oral ketamine.

OBJECTIVE: To compare the efficacy of oral ketamine (10 mg/kg) with oral midazolam (0.7 mg/kg) in providing sedation for suturing of lacerations. METHOD: Prospective, randomised, double blinded trial with consecutive, concealed recruitment of 59 children aged 1 to 7 with wounds requiring local anaesthetic (LA) injection or topical LA with an anxiety score greater than one. RESULTS: Tolerance to LA injection was better with ketamine (p=0.029) and tolerance to procedure after LA injection showed a trend towards being improved with ketamine (p=0.067). There was no difference in tolerance to LA application or procedure in children receiving topical LA. Time to reach a sedation score of less than four was faster with ketamine (medians 20 versus 43 minutes, p=0.001) but times from dosing to discharge (medians 105 and 110 minutes) were similar. Inconsolable agitation was reported with midazolam in six cases. Dysphoria was not noted with ketamine. Vomiting was more common with ketamine but not significantly so (six versus two, p = 0.14). Oxygen desaturations were noted in both groups. Ataxia after discharge was seen in four patients, two in each group. Thirty six per cent of children showed new behavioural disturbances in the two weeks after discharge, more commonly in the midazolam group (p=0.048). CONCLUSIONS: At these doses tolerance to LA injection was better in children receiving ketamine, with fewer behavioural changes noted in the first two weeks. Midazolam at this dose caused dysphoric reactions, which may have affected the results. Continuous pulse oximetry monitoring is required when using these drugs. Vomiting and prolonged ataxia occurred in a few patients.

Multicentre randomised controlled trial of nasal diamorphine for analgesia in children and teenagers with clinical fractures.

OBJECTIVE: To compare the effectiveness of nasal diamorphine spray with intramuscular morphine for analgesia in children and teenagers with acute pain due to a clinical fracture, and to describe the safety profile of the spray. DESIGN: Multicentre randomised controlled trial. SETTING: Emergency departments in eight UK hospitals. PARTICIPANTS: Patients aged between 3 and 16 years presenting with a clinical fracture of an upper or lower limb. MAIN OUTCOME MEASURES: Patients' reported pain using the Wong Baker face pain scale, ratings of reaction to treatment of the patients and acceptability of treatment by staff and parents, and adverse events. RESULTS: 404 eligible patients completed the trial (204 patients given nasal diamorphine spray and 200 given intramuscular morphine). Onset of pain relief was faster in the spray group than in the intramuscular group, with lower pain scores in the spray group at 5, 10, and 20 minutes after treatment but no difference between the groups after 30 minutes. 80% of patients given the spray showed no obvious discomfort compared with 9% given intramuscular morphine (difference 71%, 95% confidence interval 65% to 78%). Treatment administration was judged acceptable by staff and parents, respectively, for 98% (199 of 203) and 97% (186 of 192) of patients in the spray group compared with 32% (64 of 199) and 72% (142 of 197) in the intramuscular group. No serious adverse events occurred in the spray group, and the frequencies of all adverse events were similar in both groups (spray 24.1% v intramuscular morphine 18.5%; difference 5.6%, -2.3% to 13.6%). CONCLUSION: Nasal diamorphine spray should be the preferred method of pain relief in children and teenagers presenting to emergency departments in acute pain with clinical fractures. The diamorphine spray should be used in place of intramuscular morphine.

Apoaequorin monitors degradation of endoplasmic reticulum (ER) proteins initiated by loss of ER Ca(2+).

Apoaequorin was targeted to the cytosol, nucleus, and endoplasmic reticulum of HeLa cells in order to determine the effect of Ca(2+) release from the ER on protein degradation. In resting cells apoaequorin had a rapid half-life (ca. 20-30 min) in the cytosol or nucleus, but was relatively stable for up to 24 h in the ER (t(1/2) > 24 h). However, release of Ca(2+) from the ER, initiated by the addition of inhibitors of the ER Ca(2+)/Mg(2+) ATPase such as 2 microM thapsigargin or 1 microM ionomycin, initiated rapid loss of apoaequorin in the ER, but had no detectable effect on apoaequorin turnover in the cytosol nor the nucleus. This loss of apoprotein was not the result of secretion into the external fluid, and could not be inhibited by inhibitors of protein degradation by proteosomes. Proteolysis of apoaequorin in cell extracts (t(1/2) < 20 min) was completely inhibited in the presence of 1 mM Ca(2+), and this effect was independent of the ER retention signal KDEL at the C-terminus. Proteolysis was unaffected by the presence of selected serine protease inhibitors, or 10 microM Zn(2+), a known caspase-3 inhibitor. The results show that apoaequorin can monitor proteolysis of ER proteins activated by loss of ER Ca(2+). Several Ca(2+)-binding proteins exist in the ER, acting as the Ca(2+) store and chaperones. Our results have important implications both for the role of ER Ca(2+) in cell activation and stress and when using aequorin for monitoring free ER Ca(2+) over long time periods.

Point of care testing in the accident and emergency department: a cost analysis and exploration of financial incentives to use the technology within the hospital.

OBJECTIVES: To compare the costs of current arrangements for testing emergency blood samples from patients attending an accident and emergency (A&E) department in a large teaching hospital in England with point of care testing (POCT). METHODS: Estimates were made of the fixed and variable costs of two options: a supplemental option, in which POCT was introduced to A&E only; and a replacement option, in which POCT was introduced to A&E and the intensive therapy unit (ITU), thereby entirely replacing an existing process. RESULTS: For the supplemental option, current arrangements cost 68,466 Pounds in total per year; average costs per test were 5.53 Pounds (venous in the central laboratory) and 3.60 Pounds (arterial on the ITU). Introducing POCT would increase total hospital costs by 35,929 Pounds, and average costs per test would be 5.32 Pounds (venous) and 4.28 Pounds (arterial). For the replacement option, current arrangements cost 132,630 Pounds in total, and average cost per test (for all tests) was 4.06 Pounds. Introducing POCT would make hospital savings ranging from 8332 Pounds to 20,000 Pounds, and average cost per test would be 3.78 Pounds. CONCLUSIONS: Introducing POCT results in lower average costs per test. The supplemental option will result in significantly increased costs to the hospital. The replacement option can lead to significant savings. The internal cross-charging arrangements between departments that exist in this hospital may mean that supplemental implementation of POCT could be potentially 'profitable' for the A&E department, but would result in higher expenditure for the hospital as a whole.

Trafficking pathways leading to the formation of gap junctions.

This chapter reports the mechanisms resulting in the assembly of gap junction intercellular communication channels. The connexin channel protein subunits are required to oligomerize into hexameric hemichannels (connexons) that may be homoor heteromeric in composition. Pairing of connexons in contacting cells leads to the formation of a gap junction unit. Subcellular fractionation studies using guinea-pig liver showed that oligomerization of connexins was complete on entry into Golgi, and that connexons showed heteromeric properties. The low ratio of connexin26 (Cx26; beta 2) relative to Cx32 (beta 1) in endomembranes compared to the approximately equal ratios found in plasma membranes and gap junctions suggest that Cx26 takes a non-classical route to the plasma membrane. Cultured cells, expressing connexin-aequorin chimeras, also provided evidence that Cx26 takes a more rapid non-classical route to the plasma membrane, because brefeldin A, a drug that disrupts the Golgi, had minimal effects on trafficking of Cx26 to the plasma membrane in contrast to its disruption of Cx32 trafficking. Finally, a cell-free approach for studying synthesis of connexons provided further evidence that Cx26 showed membrane insertion properties compatible with a more direct intracellular route to gap junctions. The presence of dual gap junction assembly pathways can explain many of the differential properties exhibited by connexins in cells.

Intracellular trafficking pathways in the assembly of connexins into gap junctions.

Trafficking pathways underlying the assembly of connexins into gap junctions were examined using living COS-7 cells expressing a range of connexin-aequorin (Cx-Aeq) chimeras. By measuring the chemiluminescence of the aequorin fusion partner, the translocation of oligomerized connexins from intracellular stores to the plasma membrane was shown to occur at different rates that depended on the connexin isoform. Treatment of COS-7 cells expressing Cx32-Aeq and Cx43-Aeq with brefeldin A inhibited the movement of these chimera to the plasma membrane by 84 +/- 4 and 88 +/- 4%, respectively. Nocodazole treatment of the cells expressing Cx32-Aeq and Cx43-Aeq produced 29 +/- 16 and 4 +/- 7% inhibition, respectively. In contrast, the transport of Cx26 to the plasma membrane, studied using a construct (Cx26/43T-Aeq) in which the short cytoplasmic carboxyl-terminal tail of Cx26 was replaced with the extended carboxyl terminus of Cx43, was inhibited 89 +/- 5% by nocodazole and was minimally affected by exposure of cells to brefeldin A (17 +/-11%). The transfer of Lucifer yellow across gap junctions between cells expressing wild-type Cx32, Cx43, and the corresponding Cx32-Aeq and Cx43-Aeq chimeras was reduced by nocodazole treatment and abolished by brefeldin A treatment. However, the extent of dye coupling between cells expressing wild-type Cx26 or the Cx26/43T-Aeq chimeras was not significantly affected by brefeldin A treatment, but after nocodazole treatment, transfer of dye to neighboring cells was greatly reduced. These contrasting effects of brefeldin A and nocodazole on the trafficking properties and intercellular dye transfer are interpreted to suggest that two pathways contribute to the routing of connexins to the gap junction.

Connexin-aequorin chimerae report cytoplasmic calcium environments along trafficking pathways leading to gap junction biogenesis in living COS-7 cells.

The cytoplasmic calcium environments along membrane trafficking pathways leading to gap junction intercellular communication channels at the plasma membrane were studied. Connexins, the constitutive proteins of gap junctions, were fused at their carboxyl terminus to the calcium-sensitive photoprotein aequorin. The cellular location of the chimeric proteins was determined by immunolocalization and subcellular fractionation. The generation of functional gap junctions by the connexin chimerae was monitored by the ability of the cells to exchange small dyes. Although aequorin fused to connexin-26 was nonfunctional, its ability to report Ca2+ and to form functional gap junctions was rescued by replacement of its cytoplasmic carboxyl tail with that of connexin-43. In COS-7 cells expressing these connexin-aequorin chimerae, calcium levels below the plasma membrane were higher (approximately 5 microM) than those in the cytoplasm (approximately 100 nM); gap junctions were able to transfer dyes under these conditions. Cytoplasmic levels of free calcium surrounding the ERGIC/Golgi reported by connexin-43 chimera (approximately 420 nM) were twice those measured by connexin-32 chimera (approximately 200 nM); both chimerae measured calcium levels substantially higher than those reported by a connexin-26 chimera (approximately 130 nM). Dispersion of the ERGIC and Golgi complex by brefeldin A led to a marked reduction in calcium levels. The results show that the various connexin chimerae were located in spatially different subcellular stores and that the ERGIC/Golgi regions of the cell maintain heterogeneous cytoplasmic domains of calcium. The implications of the subplasma-membrane Ca2+ levels on the gating of gap junctions are discussed.

Aequorea victoria bioluminescence moves into an exciting new era.

Bioluminescence has revolutionized research into many cellular and molecular-biological processes, ranging from intracellular signalling to gene transcription. This article focuses on the chemistry and biotechnological exploitation of the two proteins involved in bioluminescence of the jellyfish Aequorea victoria--aequorin and green fluorescent protein. Engineered recombinant aequorin has led to a novel technological approach to monitoring calcium signals in organelles and subcellular domains. A new generation of intracellular calcium indicators has been produced in which engineered variants of green fluorescent protein are used to probe their ionic environment using intramolecular fluorescence-resonance-energy transfer.

Current evidence suggests independent regulation of nuclear calcium.

We review and present current evidence supporting independent regulation of nuclear Ca2+ ([Ca2+]n). The nucleus and nuclear envelope contain proteins to both regulate and respond to changes in [Ca2+]n. However, this does not prove that [Ca2+]n is independently regulated from cytosolic Ca2+ ([Ca2+]c). Studies using fluorescent dyes suggested that changes in [Ca2+]n differed in magnitude from changes in [Ca2+]c. These studies have been criticised as the nuclear environment alters the fluorescent characteristics of these dyes. We have evaluated this question with aequorin targeted to the nucleus and cytoplasm and shown that the characteristics of the indicators are not altered in their respective environments. We have demonstrated that different stimuli induce changes in [Ca2+]n and [Ca2+]c that vary both temporally and in magnitude. The nucleus appeared to be shielded from increases in [Ca2+]c, either through a mechanism involving the nuclear envelope or by cytosolic buffering of localised increases in Ca2+. In addition, agonist stimulation resulted in an increase in [Ca2+]n, consistent with release from the perinuclear Ca2+ store. There was a stimulus dependence of the relation between [Ca2+]n and [Ca2+]c suggesting differential regulation of [Ca2+]n. These results have important implications for the role of Ca2+ as a specific regulator of nuclear events through Ca2+ binding proteins. In addition, they highlight the advantages of using targeted aequorin in intact cells to monitor changes in organelle [Ca2+].

The relationship between the duration of platelet storage and the development of transfusion reactions.

BACKGROUND: The incidence of platelet transfusion reactions may depend partly on the length of storage. The influence of reactions on the effectiveness of platelet transfusions is not known. STUDY DESIGN AND METHODS: Platelet transfusion reactions, identified by prospective monitoring, were analyzed for the effects of component type, recipient lymphocytotoxic antibodies, bacterial contamination, and duration of storage. Posttransfusion corrected count increments (CCIs) were used to evaluate the effectiveness of transfusions associated with reactions by comparing them to those of randomly selected transfusions without reactions. RESULTS: Reactions accompanied 4 percent of the 4926 transfusions given and included 119 febrile nonhemolytic transfusion reactions, 62 allergic reactions, and 13 reactions with features of both. Platelet concentrates contained a mean of 0.5 x 10(8) white cells per unit. Lymphocytotoxic antibodies were detectable in 20 of 84 recipients tested proximate to a reaction. Bacterial cultures from 4 of 81 units were positive; 1 unit was associated with fatal Enterobacter sp. sepsis. The incidence of febrile nonhemolytic transfusion reactions but not allergic reactions was related to platelet storage duration. The CCI was not significantly different for transfusions associated with reactions (10.97 [median, range 0-72.5; n = 165]) or not so associated (13.1 [median, range 0-39.5; n = 174]) (p = 0.08). CONCLUSION: The incidence of febrile nonhemolytic transfusion reactions but not allergic reactions appears to be related to the duration of platelet storage. Transfusion reactions may not have an adverse impact on the effectiveness of platelet transfusions.

Assembly of chimeric connexin-aequorin proteins into functional gap junction channels. Reporting intracellular and plasma membrane calcium environments.

Chimeric proteins comprising connexins 26, 32, and 43 and aequorin, a chemiluminescent calcium indicator, were made by fusing the amino terminus of aequorin to the carboxyl terminus of connexins. The retention of function by the chimeric partners was investigated. Connexin 32-aequorin and connexin 43-aequorin retained chemiluminescent activity whereas that of connexin 26-aequorin was negligible. Immunofluorescent staining of COS-7 cells expressing the chimerae showed they were targeted to the plasma membrane. Gap junction intercellular channel formation by the chimerae alone and in combination with wild-type connexins was investigated. Stable HeLa cells expressing connexin 43-aequorin were functional, as demonstrated by Lucifer yellow transfer. Paris of Xenopus oocytes expressing connexin 43-aequorin were electrophysiologically coupled, but those expressing chimeric connexin 26 or 32 showed no detectable levels of coupling. The formation of heteromeric channels constructed of chimeric connexin 32 or connexin 43 and the respective wild-type connexins was inferred from the novel voltage gating properties of the junctional conductance. The results show that the preservation of function by each partner of the chimeric protein is dictated mainly by the nature of the connexin, especially the length of the cytoplasmic carboxyl-terminal domain. The aequorin partner of the connexin 43 chimera reported calcium levels in COS-7 cells in at least two different calcium environments.

Role of calreticulin in regulating intracellular Ca2+ storage and capacitative Ca2+ entry in HeLa cells.

Calreticulin is a Ca2+ binding protein located primarily in the endoplasmic reticulum (ER) lumen of non-excitable cells, where it is considered to be involved mainly in Ca2+ storage and buffering. However, there is increasing evidence to implicate the protein in other facets of Ca2+ signalling. In this study, we sought to establish more clearly the role of the protein in the regulation of intracellular Ca2+ signalling. Generating HeLa cells stably transfected with GFP-tagged calreticulin (GFPCRT) allowed to us to select cells by FACS in which calreticulin was expressed at ten times its endogenous levels. Using transiently expressed aequorin as a Ca2+ indicator in these cells, we investigated the role of calreticulin in intracellular Ca2+ storage, IP3-mediated Ca2+ release, and capacitative Ca2+ entry. The data showed that the capacity of the ionomycin-sensitive Ca2+ store was doubled in over-expressing cells, indicating that although calreticulin has a role in Ca2+ storage within the lumen, other lumenal proteins are also likely to be involved. No difference was observed in the release of Ca2+ from the IP3-sensitive store in response to prolonged single stimulation with histamine in the absence of extracellular Ca2+, but use of short, sequential pulses of histamine and ATP revealed that calreticulin may exert an effect upon IP3-mediated Ca2+ release. Two different experimental approaches indicated that calreticulin participates in the regulation of capacitative Ca2+ entry. In the presence of extracellular Ca2+, the histamine-generated cytosolic Ca2+ signal was significantly lower in GFPCRT cells than those in control cells. Induction of capacitative Ca2+ entry by complete emptying of the store using the SERCA pump inhibitor, cyclopiazonic acid also showed that the influx component was significantly reduced in the GFPCRT cells. Use of ER-targeted apoaequorin acting as a luciferase demonstrated that the resting ER free [Ca2+] in the GFPCRT cells was lower than that in control cells. These data implicate calreticulin in the control of IP3-mediated Ca2+ release and capacitative Ca2+ entry, which may involve direct interaction with Ca2+ signalling components or control of ER free [Ca2+].