Calcium content of different compositions of gallstones and pathogenesis of calcium carbonate gallstones.

PubMed

Yu, Ji-Kuen; Pan, Huichin; Huang, Shing-Moo; Huang, Nan-Lan; Yao, Chung-Chin; Hsiao, Kuang-Ming; Wu, Chew-Wun

2013-01-01

Our aim was to investigate the calcium content of different gallstone compositions and the pathogenic mechanisms of calcium carbonate gallstones. Between August 2001 and July 2007, gallstones from 481 patients, including 68 calcium carbonate gallstones, were analyzed for total calcium content. Gallbladder bile samples from 33 cases and six controls were analyzed for pH, carbonate anion level, free-ionized calcium concentration and saturation index for calcium carbonate. Total calcium content averaged 75.6 %, 11.8 %, and 4.2 % for calcium carbonate, calcium bilirubinate and cholesterol gallstones. In 29.4 % of patients, chronic and/or intermittent cystic duct obstructions were caused by polypoid lesions in the neck region and 70.6 % were caused by stones. A total of 82 % of patients had chronic low-grade inflammation of the gallbladder wall and 18.0 % had acute inflammatory exacerbations. In the bile, we found the mean pH, mean carbonate anion, free-ionized calcium concentrations, and mean saturation index for calcium carbonate to be elevated in comparison to controls. From our study, we found chronic and/or intermittent cystic duct obstructions and low-grade GB wall inflammation lead to GB epithelium hydrogen secretion dysfunction. Increased calcium ion efflux into the GB lumen combined with increased carbonate anion presence increases SI_CaCO(3) from 1 to 22.4. Thus, in an alkaline milieu with pH 7.8, calcium carbonate begins to aggregate and precipitate. Copyright © 2012. Published by Elsevier B.V.

Bone Up on the Need for Calcium.

ERIC Educational Resources Information Center

Mann, Peggy

1987-01-01

Most grade-schoolers drink milk at each meal, but teens, especially girls, often switch to carbonated soda at mealtime just as they should be building up their bone bank of calcium. Why calcium is important and how to get enough of it are covered. (MT)

Characterization of calcium and zinc spatial distributions at the fibrocartilage zone of bone-tendon junction by synchrotron radiation-based micro X-ray fluorescence analysis combined with backscattered electron imaging

NASA Astrophysics Data System (ADS)

Lu, Hongbin; Chen, Can; Wang, Zhanwen; Qu, Jin; Xu, Daqi; Wu, Tianding; Cao, Yong; Zhou, Jingyong; Zheng, Cheng; Hu, Jianzhong

2015-09-01

Tendon attaches to bone through a functionally graded fibrocartilage zone, including uncalcified fibrocartilage (UF), tidemark (TM) and calcified fibrocartilage (CF). This transition zone plays a pivotal role in relaxing load transfer between tendon and bone, and serves as a boundary between otherwise structurally and functionally distinct tissue types. Calcium and zinc are believed to play important roles in the normal growth, mineralization, and repair of the fibrocartilage zone of bone-tendon junction (BTJ). However, spatial distributions of calcium and zinc at the fibrocartilage zone of BTJ and their distribution-function relationship are not totally understood. Thus, synchrotron radiation-based micro X-ray fluorescence analysis (SR-μXRF) in combination with backscattered electron imaging (BEI) was employed to characterize the distributions of calcium and zinc at the fibrocartilage zone of rabbit patella-patellar tendon complex (PPTC). For the first time, the unique distributions of calcium and zinc at the fibrocartilage zone of the PPTC were clearly mapped by this method. The distributions of calcium and zinc at the fibrocartilage zone of the PPTC were inhomogeneous. A significant accumulation of zinc was exhibited in the transition region between UF and CF. The highest zinc content (3.17 times of that of patellar tendon) was found in the TM of fibrocartilage zone. The calcium content began to increase near the TM and increased exponentially across the calcified fibrocartilage region towards the patella. The highest calcium content (43.14 times of that of patellar tendon) was in the transitional zone of calcified fibrocartilage region and the patella, approximately 69 μm from the location with the highest zinc content. This study indicated, for the first time, that there is a differential distribution of calcium and zinc at the fibrocartilage zone of PPTC. These observations reveal new insights into region-dependent changes across the fibrocartilage zone of BTJ and will serve as critical benchmark parameters for current efforts in BTJ repair.

Acoustic and Hydrodynamic Cavitations for Nano CaCO3 Synthesis

NASA Astrophysics Data System (ADS)

Sonawane, Shirish H.; Kulkarni, Ravindra D.

Calcium carbonate is a common inorganic compound known as limestone. Calcium carbonate has many applications in industries such as medicine, agriculture, paint plastic and surface coatings etc. The vast majority of calcium carbonate used in industry is extracted by mining process. Pure calcium carbonate (e.g. for food or pharmaceutical use), is synthesized by passing carbon dioxide into a solution of calcium hydroxide slurry. In this process calcium carbonate precipitates out, and this grade of product is referred to as precipitate calcium carbonate (abbreviated as PCC).

Effect of Mitral Annular Calcium on Left Ventricular Diastolic Parameters.

PubMed

Codolosa, Jose N; Koshkelashvili, Nikoloz; Alnabelsi, Talal; Goykhman, Igor; Romero-Corral, Abel; Pressman, Gregg S

2016-03-01

Assessment of left ventricular (LV) diastolic function by Doppler flow imaging and tissue Doppler is an integral part of the echocardiographic examination. Mitral annular calcium (MAC) is frequently encountered on echocardiography. The aim of this study was to assess the impact of MAC, quantitatively measured by computed tomography scan, on echocardiographic LV diastolic parameters. We included 155 patients aged ≥65 years. Computed tomography reconstructions of the mitral annulus were created, and calcium identified and quantified by Agatston technique. Calcium locations were assigned using an overlaid template depicting the annular segments in relation to surrounding anatomic structures. Echocardiographic assessment of diastolic function was performed in standard fashion. Mean age was 77 years; 49% were men; and 43% were black. Patients with MAC had lower septal e' (p = 0.003), lateral e' (p = 0.04), and average e' (p = 0.01) compared with those without MAC. They also had a higher E-wave velocity (p = 0.01) and E/e' ratio (p <0.001). When evaluated by severity of MAC, and after adjustment for multiple clinical factors, there was a graded (inverse) relation between MAC severity and septal e' (p = 0.01), lateral e' (p = 0.01), and average e' (p = 0.01). In conclusion, LV diastolic parameters, as measured by Doppler echocardiography, are altered in the presence of MAC. This could be due to direct effects of MAC on annular function or might reflect truly reduced diastolic function. Interpretation of diastolic parameters in patients with MAC should be performed with caution. Copyright © 2016 Elsevier Inc. All rights reserved.

[Grade IIb alkali burns of the lower extremities. Working with concrete].

PubMed

Hasenecker, J M H; Ruchholtz, S; Eming, R; Frangen, T M

2014-01-01

The irritating effects of concrete (calcium oxide) on skin have long been known. The effect by long-term skin exposure is not only irritating but also erosive and alkali skin erosion may result due to colliquative skin necrosis. A complicated course may ensue potentially necessitating plastic reconstructive treatment due to the development of unstable scars and defects. Correct interpretation of the skin trauma and adequate treatment are mandatory for functional restitution.

Injectable Microsphere Gel Progressively Improves Global Ventricular Function, Regional Contractile Strain, and Mitral Regurgitation after Myocardial Infarction

PubMed Central

McGarvey, Jeremy R; Kondo, Norihiro; Witschey, Walter RT; Takebe, Manabu; Aoki, Chikashi; Burdick, Jason A.; Spinale, Francis G; Gorman, Joseph H; Pilla, James J; Gorman, Robert C

2014-01-01

Background There is continued need for therapies which reverse or abate the remodeling process following myocardial infarction (MI). In this study, we evaluate the longitudinal effects of calcium hydroxyapatite microsphere gel on regional strain, global ventricular function, and mitral regurgitation (MR) in a porcine MI model. Methods Twenty five Yorkshire swine were enrolled. Five were dedicated weight-matched controls. Twenty underwent posterolateral infarction by direct ligation of the circumflex artery and its branches. Infarcted animals were randomly divided into four groups: one week treatment, one week control, four week treatment, and four week control. Following infarction, animals received either twenty 150μl calcium hydroxyapatite gel or saline injections within the infarct. At their respective timepoints, echocardiograms, cardiac MRI, and tissue were collected for evaluation of MR, regional and global left ventricular function, wall thickness, and collagen content. Results Global and regional LV function were depressed in all infarcted subjects at one week compared to healthy controls. By four weeks post-infarction, global function had significantly improved in the calcium hydroxyapatite group compared to infarcted controls (EF 48.5±1.9% vs. 38.0±1.7%, p<0.01). Similarly, regional borderzone radial contractile strain (16.3±1.5% vs. 11.2±1.5%, p=0.04), MR grade (0.4±0.2 vs. 1.2±0.2, p=0.04), and infarct thickness (7.8±0.5mm vs. 4.5±0.2mm, p<0.01) were improved at this timepoint in the treatment group compared to infarct controls. Conclusions Calcium hydroxyapatite injection following MI progressively improves global LV function, borderzone function, and mitral regurgitation. Using novel biomaterials to augment infarct material properties is viable alternative in the current management of heart failure. PMID:25524397

7 CFR 58.434 - Calcium chloride.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., GENERAL SPECIFICATIONS FOR APPROVED PLANTS AND STANDARDS FOR GRADES OF DAIRY PRODUCTS 1 General Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw... Chemical Codex. ...

7 CFR 58.434 - Calcium chloride.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., GENERAL SPECIFICATIONS FOR APPROVED PLANTS AND STANDARDS FOR GRADES OF DAIRY PRODUCTS 1 General Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw... Chemical Codex. ...

7 CFR 58.434 - Calcium chloride.

Code of Federal Regulations, 2012 CFR

2012-01-01

..., GENERAL SPECIFICATIONS FOR APPROVED PLANTS AND STANDARDS FOR GRADES OF DAIRY PRODUCTS 1 General Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw... Chemical Codex. ...

Nanofiber scaffold gradients for interfacial tissue engineering.

PubMed

Ramalingam, Murugan; Young, Marian F; Thomas, Vinoy; Sun, Limin; Chow, Laurence C; Tison, Christopher K; Chatterjee, Kaushik; Miles, William C; Simon, Carl G

2013-02-01

We have designed a 2-spinnerette device that can directly electrospin nanofiber scaffolds containing a gradient in composition that can be used to engineer interfacial tissues such as ligament and tendon. Two types of nanofibers are simultaneously electrospun in an overlapping pattern to create a nonwoven mat of nanofibers containing a composition gradient. The approach is an advance over previous methods due to its versatility - gradients can be formed from any materials that can be electrospun. A dye was used to characterize the 2-spinnerette approach and applicability to tissue engineering was demonstrated by fabricating nanofibers with gradients in amorphous calcium phosphate nanoparticles (nACP). Adhesion and proliferation of osteogenic cells (MC3T3-E1 murine pre-osteoblasts) on gradients was enhanced on the regions of the gradients that contained higher nACP content yielding a graded osteoblast response. Since increases in soluble calcium and phosphate ions stimulate osteoblast function, we measured their release and observed significant release from nanofibers containing nACP. The nanofiber-nACP gradients fabricated herein can be applied to generate tissues with osteoblast gradients such as ligaments or tendons. In conclusion, these results introduce a versatile approach for fabricating nanofiber gradients that can have application for engineering graded tissues.

Biocomposites and hybrid biomaterials based on calcium orthophosphates

PubMed Central

Dorozhkin, Sergey V.

2011-01-01

The state-of-the-art of biocomposites and hybrid biomaterials based on calcium orthophosphates that are suitable for biomedical applications is presented in this review. Since these types of biomaterials offer many significant and exciting possibilities for hard tissue regeneration, this subject belongs to a rapidly expanding area of biomedical research. Through successful combinations of the desired properties of matrix materials with those of fillers (in such systems, calcium orthophosphates might play either role), innovative bone graft biomaterials can be designed. Various types of biocomposites and hybrid biomaterials based on calcium orthophosphates, either those already in use or being investigated for biomedical applications, are extensively discussed. Many different formulations, in terms of the material constituents, fabrication technologies, structural and bioactive properties as well as both in vitro and in vivo characteristics, have already been proposed. Among the others, the nanostructurally controlled biocomposites, those containing nanodimensional compounds, biomimetically fabricated formulations with collagen, chitin and/or gelatin as well as various functionally graded structures seem to be the most promising candidates for clinical applications. The specific advantages of using biocomposites and hybrid biomaterials based on calcium orthophosphates in the selected applications are highlighted. As the way from the laboratory to the hospital is a long one, and the prospective biomedical candidates have to meet many different necessities, this review also examines the critical issues and scientific challenges that require further research and development. PMID:23507726

Impact of functionalized particle structure on roll compaction/dry granulation and tableting of calcium carbonate.

PubMed

Grote, Simon; Kleinebudde, Peter

2018-06-10

The influence of a functionalized raw material particle structure on the granulation behavior and tabletabilty of calcium carbonate (CaCO 3 ) was investigated. Therefore, a milled grade of CaCO 3 was compared to different binary mixtures of milled and functionalized CaCO 3 . Relevant properties of raw materials, ribbons and granules were measured. The starting materials and two fractions of dry granules were compressed to tablets. The tabletability of granules was compared to that of the powders and the influence of specific compaction force and granule size on tablet tensile strength was evaluated. Adding functionalized particles drastically influenced the granulation and tableting behavior of CaCO 3 . Increasing proportions increased the ribbon porosity and granule size. Tensile strength of tablets from powder mixtures and granules was increased as well. Nevertheless, adding functionalized CaCO 3 led to a loss in tabletability induced by a previous compaction step to an extent depending on its proportion in the formulation. A clear influence of the particle morphology on granulation and tableting behavior was demonstrated by the study. The functionalized structure showed aspects of a more plastic deformation behavior. Adding functionalized CaCO 3 to a mixture, even in small amounts, seemed to be beneficial to increase granule size and tablet strength. Copyright © 2018 Elsevier B.V. All rights reserved.

Use of fly ash in diets of cage and floor broilers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pharr, C.L.; Andrews, L.D.

1980-09-01

Three experiments were conducted to compare limestone to fly ash from a coal-fired generator station as a calcium source for broilers. In experiment 1, 5 male and 5 female broiler chicks were placed in each of 32 cages. Sixteen cages of birds were fed a ration with limestone supplying 30% of the total calcium and 16 cages were fed a ration with 30% of the total calcium supplied by fly ash. The total calcium and phosphorus levels of the rations were 1.0% and .5%, respectively. In this experiment no significant difference was found for 8-week body weight between diets wheremore » the added calcium was from limestone or fly ash. In experiment 2 a group of 40 male and 40 female cage reared broilers and 40 male and 40 female floor reared broilers were fed a basal diet of limestone providing 33% of the total calcium. Three diets with increasing fly ash levels were fed to three cage groups of 40 male and 40 female broilers providing 33, 46, and 45% of the total calcium of .9, 1.1, and 1.8%, respectively. Broilers fed the highest fly ash level weighed significantly less at 8 weeks than the caged controls but did not differ from the other treatments. Bone breaking strength as measured by the Allo Kramer Shear Press was similar between the basal and low level fly ash group and increased with higher fly ash levels. In experiment 3 four groups of 40 male broilers in cages were fed limestone diets with graded levels of limestone for the calcium source. Another four groups of 40 caged male broilers were fed fly ash diets with equivalent graded levels of fly ash for the calcium source. Both limestone and fly ash diets provided .17, .34, .51, and .68% calcium of a total calcium content of .28, .45, .62, and .79%, respectively.« less

Oral manifestations in a renal osteodystrophy patient - a case report with review of literature.

PubMed

J, Parthiban; Nisha V, Aarthi; Gs, Asokan; Ca, Prakash; Mm, Varadharaja

2014-08-01

Renal Osteodystrophy (ROD) is a common complication of chronic renal disease (CRD) and is the part of a broad spectrum of disorders of mineral metabolism that occurs in the clinical setting. It occurs early in the course of chronic renal failure and progresses as the kidney function deteriorates. It is an osseous alteration believed to arise from increased parathyroid function associated with inappropriate calcium, phosphorus and vitamin D metabolism. Involvement of the jaws is common and radiographic alterations are often one of the earliest signs of chronic renal failure. Herein, reporting a case of Chronic Renal Failure (Bilateral Grade I Neuropathy) with ROD presenting oral manifestations in an 11-year -old male child.

75 FR 43146 - Saccharin From the People's Republic of China: Final Results of the 2008-2009 Antidumping Duty...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-23

.... SUPPLEMENTARY INFORMATION: Background On March 22, 2010, the Department published its Preliminary Results of the... Society Chemical Abstract Service (``CAS'') Registry 128-44-9); (2) calcium saccharin (CAS Registry 6485.... Most of the U.S.-produced and imported grades of saccharin from the PRC are sodium and calcium...

Histopathological Evaluation of the Anterior Cruciate Ligament in Patients Undergoing Primary Total Knee Arthroplasty.

PubMed

Mont, Michael A; Elmallah, Randa K; Cherian, Jeffrey J; Banerjee, Samik; Kapadia, Bhaveen H

2016-01-01

This study assessed gross and histopathological ACL changes in arthritic knees (n=174) undergoing total knee arthroplasty. Histopathological changes were assessed and graded as absent (0), mild (1), moderate (2), or marked (3). These were correlated to demographic and clinical factors, and radiographic evaluations. The ACL was intact in 43, frayed in 85, torn in 15, and absent in 31 knees. Eighty-five percent had histological changes. Overall, there were significant associations between greater age and BMI, and histological changes. Grade IV knees had significantly greater calcium pyrophosphate deposits, microcyst formation, and number of pathologic changes. These correlations may aid decision-making when determining suitability for unicompartmental or bicruciate-retaining arthroplasties, though further studies should correlate these histological findings to mechanical and functional knee status. Copyright © 2016 Elsevier Inc. All rights reserved.

Rheology and extrusion of low-grade paper and sludge

Treesearch

C. Tim Scott; Stefan Zauscher; Daniel J. Klingenberg

1999-01-01

This paper discusses efforts to characterize the rheological properties of pulps that include low-grade wastepapers and papermill sludges to determine their potential for extrusion and conversion into useful products. We investigated apparent changes in viscosity associated with the addition of typical inorganic paper fillers (calcium carbonate, kaolin clay, and...

Synthesis of Portland cement and calcium sulfoaluminate-belite cement for sustainable development and performance

NASA Astrophysics Data System (ADS)

Chen, Irvin Allen

Portland cement concrete, the most widely used manufactured material in the world, is made primarily from water, mineral aggregates, and portland cement. The production of portland cement is energy intensive, accounting for 2% of primary energy consumption and 5% of industrial energy consumption globally. Moreover, portland cement manufacturing contributes significantly to greenhouse gases and accounts for 5% of the global CO2 emissions resulting from human activity. The primary objective of this research was to explore methods of reducing the environmental impact of cement production while maintaining or improving current performance standards. Two approaches were taken, (1) incorporation of waste materials in portland cement synthesis, and (2) optimization of an alternative environmental friendly binder, calcium sulfoaluminate-belite cement. These approaches can lead to less energy consumption, less emission of CO2, and more reuse of industrial waste materials for cement manufacturing. In the portland cement part of the research, portland cement clinkers conforming to the compositional specifications in ASTM C 150 for Type I cement were successfully synthesized from reagent-grade chemicals with 0% to 40% fly ash and 0% to 60% slag incorporation (with 10% intervals), 72.5% limestone with 27.5% fly ash, and 65% limestone with 35% slag. The synthesized portland cements had similar early-age hydration behavior to commercial portland cement. However, waste materials significantly affected cement phase formation. The C3S--C2S ratio decreased with increasing amounts of waste materials incorporated. These differences could have implications on proportioning of raw materials for cement production when using waste materials. In the calcium sulfoaluminate-belite cement part of the research, three calcium sulfoaluminate-belite cement clinkers with a range of phase compositions were successfully synthesized from reagent-grade chemicals. The synthesized calcium sulfoaluminate-belite cement that contained medium C4A3 S¯ and C2S contents showed good dimensional stability, sulfate resistance, and compressive strength development and was considered the optimum phase composition for calcium sulfoaluminate-belite cement in terms of comparable performance characteristics to portland cement. Furthermore, two calcium sulfoaluminate-belite cement clinkers were successfully synthesized from natural and waste materials such as limestone, bauxite, flue gas desulfurization sludge, Class C fly ash, and fluidized bed ash proportioned to the optimum calcium sulfoaluminate-belite cement synthesized from reagent-grade chemicals. Waste materials composed 30% and 41% of the raw ingredients. The two calcium sulfoaluminate-belite cements synthesized from natural and waste materials showed good dimensional stability, sulfate resistance, and compressive strength development, comparable to commercial portland cement.

Localized intracellular calcium signaling in muscle: calcium sparks and calcium quarks.

PubMed

Niggli, E

1999-01-01

Subcellularly localized Ca2+ signals in cardiac and skeletal muscle have recently been identified as elementary Ca2+ signaling events. The signals, termed Ca2+ sparks and Ca2+ quarks, represent openings of Ca2+ release channels located in the membrane of the sarcoplasmic reticulum (SR). In cardiac muscle, the revolutionary discovery of Ca2+ sparks has allowed the development of a fundamentally different concept for the amplification of Ca2+ signals by Ca(2+)-induced Ca2+ release. In such a system, a graded amplification of the triggering Ca2+ signal entering the myocyte via L-type Ca2+ channels is accomplished by a recruitment process whereby individual SR Ca2+ release units are locally controlled by L-type Ca2+ channels. In skeletal muscle, the initial SR Ca2+ release is governed by voltage-sensors but subsequently activates additional Ca2+ sparks by Ca(2+)-induced Ca2+ release from the SR. Results from studies on elementary Ca2+ release events will improve our knowledge of muscle Ca2+ signaling at all levels of complexity, from the molecule to normal cellular function, and from the regulation of cardiac and skeletal muscle force to the pathophysiology of excitation-contraction coupling.

Conversion of calcium sulphide to calcium carbonate during the process of recovery of elemental sulphur from gypsum waste.

PubMed

de Beer, M; Maree, J P; Liebenberg, L; Doucet, F J

2014-11-01

The production of elemental sulphur and calcium carbonate (CaCO3) from gypsum waste can be achieved by thermally reducing the waste into calcium sulphide (CaS), which is then subjected to a direct aqueous carbonation step for the generation of hydrogen sulphide (H2S) and CaCO3. H2S can subsequently be converted to elemental sulphur via the commercially available chemical catalytic Claus process. This study investigated the carbonation of CaS by examining both the solution chemistry of the process and the properties of the formed carbonated product. CaS was successfully converted into CaCO3; however, the reaction yielded low-grade carbonate products (i.e. <90 mass% as CaCO3) which comprised a mixture of two CaCO3 polymorphs (calcite and vaterite), as well as trace minerals originating from the starting material. These products could replace the Sappi Enstra CaCO3 (69 mass% CaCO3), a by-product from the paper industry which is used in many full-scale AMD neutralisation plants but is becoming insufficient. The insight gained is now also being used to develop and optimize an indirect aqueous CaS carbonation process for the production of high-grade CaCO3 (i.e. >99 mass% as CaCO3) or precipitated calcium carbonate (PCC). Copyright © 2014 Elsevier Ltd. All rights reserved.

Synthesis of high-purity precipitated calcium carbonate during the process of recovery of elemental sulphur from gypsum waste.

PubMed

de Beer, M; Doucet, F J; Maree, J P; Liebenberg, L

2015-12-01

We recently showed that the production of elemental sulphur and calcium carbonate (CaCO3) from gypsum waste by thermally reducing the waste into calcium sulphide (CaS) followed by its direct aqueous carbonation yielded low-grade carbonate products (i.e. <90 mass% as CaCO3). In this study, we used the insight gained from our previous work and developed an indirect aqueous CaS carbonation process for the production of high-grade CaCO3 (i.e. >99 mass% as CaCO3) or precipitated calcium carbonate (PCC). The process used an acid gas (H2S) to improve the aqueous dissolution of CaS, which is otherwise poorly soluble. The carbonate product was primarily calcite (99.5%) with traces of quartz (0.5%). Calcite was the only CaCO3 polymorph obtained; no vaterite or aragonite was detected. The product was made up of micron-size particles, which were further characterised by XRD, TGA, SEM, BET and true density. Results showed that about 0.37 ton of high-grade PCC can be produced from 1.0 ton of gypsum waste, and generates about 0.19 ton of residue, a reduction of 80% from original waste gypsum mass to mass of residue that needs to be discarded off. The use of gypsum waste as primary material in replacement of mined limestone for the production of PPC could alleviate waste disposal problems, along with converting significant volumes of waste materials into marketable commodities. Copyright © 2015 Elsevier Ltd. All rights reserved.

Activity-Dependent Gating of Calcium Spikes by A-type K+ Channels Controls Climbing Fiber Signaling in Purkinje Cell Dendrites

PubMed Central

Otsu, Yo; Marcaggi, Païkan; Feltz, Anne; Isope, Philippe; Kollo, Mihaly; Nusser, Zoltan; Mathieu, Benjamin; Kano, Masanobu; Tsujita, Mika; Sakimura, Kenji; Dieudonné, Stéphane

2014-01-01

Summary In cerebellar Purkinje cell dendrites, heterosynaptic calcium signaling induced by the proximal climbing fiber (CF) input controls plasticity at distal parallel fiber (PF) synapses. The substrate and regulation of this long-range dendritic calcium signaling are poorly understood. Using high-speed calcium imaging, we examine the role of active dendritic conductances. Under basal conditions, CF stimulation evokes T-type calcium signaling displaying sharp proximodistal decrement. Combined mGluR1 receptor activation and depolarization, two activity-dependent signals, unlock P/Q calcium spikes initiation and propagation, mediating efficient CF signaling at distal sites. These spikes are initiated in proximal smooth dendrites, independently from somatic sodium action potentials, and evoke high-frequency bursts of all-or-none fast-rising calcium transients in PF spines. Gradual calcium spike burst unlocking arises from increasing inactivation of mGluR1-modulated low-threshold A-type potassium channels located in distal dendrites. Evidence for graded activity-dependent CF calcium signaling at PF synapses refines current views on cerebellar supervised learning rules. PMID:25220810

Calcium Orthophosphates in Nature, Biology and Medicine

PubMed Central

Dorozhkin, Sergey V.

2009-01-01

The present overview is intended to point the readers’ attention to the important subject of calcium orthophosphates. These materials are of the special significance because they represent the inorganic part of major normal (bones, teeth and dear antlers) and pathological (i.e. those appearing due to various diseases) calcified tissues of mammals. Due to a great chemical similarity with the biological calcified tissues, many calcium orthophosphates possess remarkable biocompatibility and bioactivity. Materials scientists use this property extensively to construct artificial bone grafts that are either entirely made of or only surface-coated with the biologically relevant calcium ortho-phosphates. For example, self-setting hydraulic cements made of calcium orthophosphates are helpful in bone repair, while titanium substitutes covered by a surface layer of calcium orthophosphates are used for hip joint endoprostheses and as tooth substitutes. Porous scaffolds made of calcium orthophosphates are very promising tools for tissue engineering applications. In addition, technical grade calcium orthophosphates are very popular mineral fertilizers. Thus ere calcium orthophosphates are of great significance for humankind and, in this paper, an overview on the current knowledge on this subject is provided.

Activity-dependent gating of calcium spikes by A-type K+ channels controls climbing fiber signaling in Purkinje cell dendrites.

PubMed

Otsu, Yo; Marcaggi, Païkan; Feltz, Anne; Isope, Philippe; Kollo, Mihaly; Nusser, Zoltan; Mathieu, Benjamin; Kano, Masanobu; Tsujita, Mika; Sakimura, Kenji; Dieudonné, Stéphane

2014-10-01

In cerebellar Purkinje cell dendrites, heterosynaptic calcium signaling induced by the proximal climbing fiber (CF) input controls plasticity at distal parallel fiber (PF) synapses. The substrate and regulation of this long-range dendritic calcium signaling are poorly understood. Using high-speed calcium imaging, we examine the role of active dendritic conductances. Under basal conditions, CF stimulation evokes T-type calcium signaling displaying sharp proximodistal decrement. Combined mGluR1 receptor activation and depolarization, two activity-dependent signals, unlock P/Q calcium spikes initiation and propagation, mediating efficient CF signaling at distal sites. These spikes are initiated in proximal smooth dendrites, independently from somatic sodium action potentials, and evoke high-frequency bursts of all-or-none fast-rising calcium transients in PF spines. Gradual calcium spike burst unlocking arises from increasing inactivation of mGluR1-modulated low-threshold A-type potassium channels located in distal dendrites. Evidence for graded activity-dependent CF calcium signaling at PF synapses refines current views on cerebellar supervised learning rules. Copyright © 2014 Elsevier Inc. All rights reserved.

Calcium content and high calcium adaptation of plants in karst areas of southwestern Hunan, China

NASA Astrophysics Data System (ADS)

Wei, Xiaocong; Deng, Xiangwen; Xiang, Wenhua; Lei, Pifeng; Ouyang, Shuai; Wen, Hongfang; Chen, Liang

2018-05-01

Rocky desertification is a major ecological problem of land degradation in karst areas. In these areas, the high soil calcium (Ca) content has become an important environmental factor that can affect the restoration of vegetation. Consequently, the screening of plant species that can adapt to high Ca soil environments is a critical step in vegetation restoration. In this study, three grades of rocky desertification sample areas were selected in karst areas of southwestern Hunan, China (LRD: light rocky desertification; MRD: moderate rocky desertification; and IRD: intense rocky desertification). Each grade of these sample areas had three sample plots in different slope positions, each of which had four small quadrats (one in rocky-side areas, three in non-rocky-side areas). We measured the Ca content of leaves, branches, and roots from 41 plant species, as well as soil total Ca (TCa) and exchangeable Ca (ECa) at depths of 0-15, 15-30, and 30-45 cm in each small quadrat. The results showed that the soil Ca2+ content in rocky-side areas was significantly higher than that in non-rocky-side areas (p < 0.05). The mean soil TCa and ECa content increased gradually along with the grade of rocky desertification, in the order IRD > MRD > LRD. For all plant functional groups, the plant Ca content of aboveground parts was significantly higher than that of the belowground parts (p < 0.05). The soil ECa content had significant effects on plant Ca content of the belowground parts but had no significant effects on plant Ca content of the aboveground parts. Of the 41 plant species that were sampled, 17 were found to be dominant (important value > 1). The differences in Ca2+ content between the aboveground and belowground parts of the 17 dominant species were calculated, and their correlations with soil ECa content were analyzed. The results showed that these 17 species can be divided into three categories: Ca-indifferent plants, high-Ca plants, and low-Ca plants. These findings provide a vital theoretical basis and practical guide for vegetation restoration and ecosystem reconstruction in rocky desertification areas.

The impact of age and frailty on ventricular structure and function in C57BL/6J mice

PubMed Central

Feridooni, H. A.; Kane, A. E.; Ayaz, O.; Boroumandi, A.; Polidovitch, N.; Tsushima, R. G.; Rose, R. A.

2017-01-01

Key points Heart size increases with age (called hypertrophy), and its ability to contract declines. However, these reflect average changes that may not be present, or present to the same extent, in all older individuals.That aging happens at different rates is well accepted clinically. People who are aging rapidly are frail and frailty is measured with a ‘frailty index’.We quantified frailty with a validated mouse frailty index tool and evaluated the impacts of age and frailty on cardiac hypertrophy and contractile dysfunction.Hypertrophy increased with age, while contractions, calcium currents and calcium transients declined; these changes were graded by frailty scores.Overall health status, quantified as frailty, may promote maladaptive changes associated with cardiac aging and facilitate the development of diseases such as heart failure.To understand age‐related changes in heart structure and function, it is essential to know both chronological age and the health status of the animal. Abstract On average, cardiac hypertrophy and contractile dysfunction increase with age. Still, individuals age at different rates and their health status varies from fit to frail. We investigated the influence of frailty on age‐dependent ventricular remodelling. Frailty was quantified as deficit accumulation in adult (≈7 months) and aged (≈27 months) C57BL/6J mice by adapting a validated frailty index (FI) tool. Hypertrophy and contractile function were evaluated in Langendorff‐perfused hearts; cellular correlates/mechanisms were investigated in ventricular myocytes. FI scores increased with age. Mean cardiac hypertrophy increased with age, but values in the adult and aged groups overlapped. When plotted as a function of frailty, hypertrophy was graded by FI score (r = 0.67–0.55, P < 0.0003). Myocyte area also correlated positively with FI (r = 0.34, P = 0.03). Left ventricular developed pressure (LVDP) plus rates of pressure development (+dP/dt) and decay (−dP/dt) declined with age and this was graded by frailty (r = −0.51, P = 0.0007; r = −0.48, P = 0.002; r = −0.56, P = 0.0002 for LVDP, +dP/dt and −dP/dt). Smaller, slower contractions graded by FI score were also seen in ventricular myocytes. Contractile dysfunction in cardiomyocytes isolated from frail mice was attributable to parallel changes in underlying Ca2+ transients. These changes were not due to reduced sarcoplasmic reticulum stores, but were graded by smaller Ca2+ currents (r = −0.40, P = 0.008), lower gain (r = −0.37, P = 0.02) and reduced expression of Cav1.2 protein (r = −0.68, P = 0.003). These results show that cardiac hypertrophy and contractile dysfunction in naturally aging mice are graded by overall health and suggest that frailty, in addition to chronological age, can help explain heterogeneity in cardiac aging. PMID:28502095

Oral Manifestations in a Renal Osteodystrophy Patient - A Case Report with Review of Literature

PubMed Central

Nisha V, Aarthi; GS, Asokan; CA, Prakash; MM, Varadharaja

2014-01-01

Renal Osteodystrophy (ROD) is a common complication of chronic renal disease (CRD) and is the part of a broad spectrum of disorders of mineral metabolism that occurs in the clinical setting. It occurs early in the course of chronic renal failure and progresses as the kidney function deteriorates. It is an osseous alteration believed to arise from increased parathyroid function associated with inappropriate calcium, phosphorus and vitamin D metabolism. Involvement of the jaws is common and radiographic alterations are often one of the earliest signs of chronic renal failure. Herein, reporting a case of Chronic Renal Failure (Bilateral Grade I Neuropathy) with ROD presenting oral manifestations in an 11-year -old male child. PMID:25302278

Cetuximab-induced hypomagnesaemia aggravates peripheral sensory neurotoxicity caused by oxaliplatin

PubMed Central

Satomi, Machiko; Asama, Toshiyuki; Ebisawa, Yoshiaki; Chisato, Naoyuki; Suno, Manabu; Karasaki, Hidenori; Furukawa, Hiroyuki; Matsubara, Kazuo

2010-01-01

Calcium and magnesium replacement is effective in reducing oxaliplatin-induced neurotoxicity. However, cetuximab treatment has been associated with severe hypomagnesaemia. Therefore, we retrospectively investigated whether cetuximab-induced hypomagnesaemia exacerbated oxaliplatin-induced neurotoxicity. Six patients with metastatic colorectal cancer who were previously treated with oxaliplatin-fluorouracil combination therapy were administered cetuximab in combination with irinotecan alone or irinotecan and fluorouracil as a second-line treatment. All patients had normal magnesium levels before receiving cetuximab. The Common Terminology Criteria for Adverse Events version 3.0 was used to evaluate the grade of neurotoxicity, hypomagnesaemia, hypocalcaemia, and hypokalemia every week. All six patients had grade 1 or higher hypomagnesaemia after starting cetuximab therapy. The serum calcium and potassium levels were within the normal range at the onset of hypomagnesaemia. Oxaliplatin-induced neurotoxicity occurred in all patients at the beginning of cetuximab therapy, with grade 1 neurotoxicity in five patients and grade 2 in one patient. After cetuximab administration, the neurotoxicity worsened in all six patients, and three progressed to grade 3. Among the three patients with grade 3 neurotoxicity, two required a dose reduction and one had to discontinue cetuximab therapy. A discontinuation or dose reduction in cetuximab therapy was associated with exacerbated oxaliplatin-induced neurotoxicity due to cetuximab-induced hypomagnesaemia in half of patients who had previously received oxaliplatin. Therefore, when administering cetuximab after oxaliplatin therapy, we suggest serially evaluating serum magnesium levels and neurotoxicity. PMID:22811813

Toward an Integrative Computational Model of the Guinea Pig Cardiac Myocyte

PubMed Central

Gauthier, Laura Doyle; Greenstein, Joseph L.; Winslow, Raimond L.

2012-01-01

The local control theory of excitation-contraction (EC) coupling asserts that regulation of calcium (Ca2+) release occurs at the nanodomain level, where openings of single L-type Ca2+ channels (LCCs) trigger openings of small clusters of ryanodine receptors (RyRs) co-localized within the dyad. A consequence of local control is that the whole-cell Ca2+ transient is a smooth continuous function of influx of Ca2+ through LCCs. While this so-called graded release property has been known for some time, its functional importance to the integrated behavior of the cardiac ventricular myocyte has not been fully appreciated. We previously formulated a biophysically based model, in which LCCs and RyRs interact via a coarse-grained representation of the dyadic space. The model captures key features of local control using a low-dimensional system of ordinary differential equations. Voltage-dependent gain and graded Ca2+ release are emergent properties of this model by virtue of the fact that model formulation is closely based on the sub-cellular basis of local control. In this current work, we have incorporated this graded release model into a prior model of guinea pig ventricular myocyte electrophysiology, metabolism, and isometric force production. The resulting integrative model predicts the experimentally observed causal relationship between action potential (AP) shape and timing of Ca2+ and force transients, a relationship that is not explained by models lacking the graded release property. Model results suggest that even relatively subtle changes in AP morphology that may result, for example, from remodeling of membrane transporter expression in disease or spatial variation in cell properties, may have major impact on the temporal waveform of Ca2+ transients, thus influencing tissue level electromechanical function. PMID:22783206

Toward an integrative computational model of the Guinea pig cardiac myocyte.

PubMed

Gauthier, Laura Doyle; Greenstein, Joseph L; Winslow, Raimond L

2012-01-01

The local control theory of excitation-contraction (EC) coupling asserts that regulation of calcium (Ca(2+)) release occurs at the nanodomain level, where openings of single L-type Ca(2+) channels (LCCs) trigger openings of small clusters of ryanodine receptors (RyRs) co-localized within the dyad. A consequence of local control is that the whole-cell Ca(2+) transient is a smooth continuous function of influx of Ca(2+) through LCCs. While this so-called graded release property has been known for some time, its functional importance to the integrated behavior of the cardiac ventricular myocyte has not been fully appreciated. We previously formulated a biophysically based model, in which LCCs and RyRs interact via a coarse-grained representation of the dyadic space. The model captures key features of local control using a low-dimensional system of ordinary differential equations. Voltage-dependent gain and graded Ca(2+) release are emergent properties of this model by virtue of the fact that model formulation is closely based on the sub-cellular basis of local control. In this current work, we have incorporated this graded release model into a prior model of guinea pig ventricular myocyte electrophysiology, metabolism, and isometric force production. The resulting integrative model predicts the experimentally observed causal relationship between action potential (AP) shape and timing of Ca(2+) and force transients, a relationship that is not explained by models lacking the graded release property. Model results suggest that even relatively subtle changes in AP morphology that may result, for example, from remodeling of membrane transporter expression in disease or spatial variation in cell properties, may have major impact on the temporal waveform of Ca(2+) transients, thus influencing tissue level electromechanical function.

Mechanical and physical behavior of newly developed functionally graded materials and composites of stainless steel 316L with calcium silicate and hydroxyapatite.

PubMed

Ataollahi Oshkour, Azim; Pramanik, Sumit; Mehrali, Mehdi; Yau, Yat Huang; Tarlochan, Faris; Abu Osman, Noor Azuan

2015-09-01

This study aimed to investigate the structural, physical and mechanical behavior of composites and functionally graded materials (FGMs) made of stainless steel (SS-316L)/hydroxyapatite (HA) and SS-316L/calcium silicate (CS) employing powder metallurgical solid state sintering. The structural analysis using X-ray diffraction showed that the sintering at high temperature led to the reaction between compounds of the SS-316L and HA, while SS-316L and CS remained intact during the sintering process in composites of SS-316L/CS. A dimensional expansion was found in the composites made of 40 and 50 wt% HA. The minimum shrinkage was emerged in 50 wt% CS composite, while the maximum shrinkage was revealed in samples with pure SS-316L, HA and CS. Compressive mechanical properties of SS-316L/HA decreased sharply with increasing of HA content up to 20 wt% and gradually with CS content up to 50 wt% for SS-316L/CS composites. The mechanical properties of the FGM of SS-316L/HA dropped with increase in temperature, while it was improved for the FGM of SS-316L/CS with temperature enhancement. It has been found that the FGMs emerged a better compressive mechanical properties compared to both the composite systems. Therefore, the SS-316L/CS composites and their FGMs have superior compressive mechanical properties to the SS-316L/HA composites and their FGMs and also the newly developed FGMs of SS-316L/CS with improved mechanical and enhanced gradation in physical and structural properties can potentially be utilized in the components with load-bearing application. Copyright © 2015 Elsevier Ltd. All rights reserved.

An improved kilogram-scale preparation of atorvastatin calcium.

PubMed

Novozhilov, Yuri V; Dorogov, Mikhail V; Blumina, Maria V; Smirnov, Alexey V; Krasavin, Mikhail

2015-01-01

If literature protocols are followed, conversion of an advanced ketal ester intermediate (available in kilogram quantities via a published Paal-Knorr synthesis) to cholesterol-lowering drug atorvastatin calcium is hampered by several process issues, particularly at the final stage where the hemi-calcium salt is obtained. We developed a high-yielding synthesis of atorvastatin calcium salt on 7 kg scale that affords >99.5% product purities by introducing the following key improvements: i. isolating the pure product of the ketal deprotection step as crystalline solid, and ii. using a convenient ethyl acetate extraction procedure to isolate the pure atorvastatin calcium at the ester hydrolysis and counter-ion exchange step. The convenient and operationally simple conversion of an advanced intermediate of atorvastatin to the clinically used hemi-calcium salt form of the drug that is superior to the methods obtainable from the literature is now available to facilitate the production of atorvastatin calcium on industrial scale. Graphical abstractStepwise ketal and tert-butyl ester group hydrolysis and a modified work-up protocol lead to a more convenient preparation of API-grade atorvastatin calcium.

Effect of chloride ion concentration on the galvanic corrosion of α phase brass by eccrine sweat.

PubMed

Meekins, Andrew; Bond, John W; Chaloner, Penelope

2012-07-01

Inductively coupled plasma mass spectrometry measurement of the relative concentration of sodium, chloride, calcium, and potassium ions in eccrine sweat deposits from 40 donors revealed positive correlations between chloride and sodium (ρ = 0.684, p < 0.01) and chloride and calcium ions (ρ = 0.91, p < 0.01). Correlations between ion concentration and the corrosion of α phase brass by the donated sweat were investigated by visual grading of the degree of corrosion, by measuring the copper/zinc ratio using energy-dispersive X-ray spectroscopy, and from a measurement of the potential difference between corroded and uncorroded brass when a large potential was applied to the uncorroded brass. An increasing copper/zinc ratio (indicative of dezincification) was found to correlate positively to both chloride ion concentration and visual grading of corrosion, while visual grading gave correlations with potential difference measurements that were indicative of the preferential surface oxidation of zinc rather than copper. © 2012 American Academy of Forensic Sciences.

Metamorphic mineral assemblages of slightly calcic pelitic rocks in and around the Taconic Allochthon, southwestern Massachusetts and adjacent Connecticut and New York

USGS Publications Warehouse

Zen, E-an

1981-01-01

The mineral assemblages from metamorphosed slightly calcic pelitic rocks of the Taconic Range in southwestern Massachusetts and adjacent areas of Connecticut and New York were studied petrographically and chemically. These rocks vary in metamorphic grade from those below the chloritoid zone through the chloritoid and garnet zones into the kyanite-staurolite zone. Microprobe data on the ferromagnesian minerals show that the sequence of increasing Fe/ (Fe+Mg) value is, from the lowest, chlorite, biotite, hornblende, chloritoid, staurolite, garnet. Hornblende, epidote, garnet, and plagioclase are the most common minerals that carry significant calcium. Biotite is persistently deficient in alkali but is abnormally rich in octahedral aluminum to such an extent that the overall charge balance can be ascribed to an AI=K+ (Fe,Mg) diadochy. Muscovite contains small though persistent amounts of iron and magnesium in octahedral positions but has a variable K/Na ratio, which is potentially useful as a geothermometer. One low-grade muscovite is highly phengitic, but the white micas in rocks from metamorphic grades higher than chloritoid zone do not contain significant phengite components. Chlorite is persistently high in aluminum and so its ratio of divalent ions to aluminum is approximately that of garnet. Many garnets show pronounced zoning in manganese and less pronounced zoning in calcium. Garnet coexisting with hornblende contains a high proportion of the grossularitic component. The calcium content is significant in all the analyzed garnets, except those from a cummingtonite-bearing sample that is free of muscovite. This suggests that in slightly calcic pelitic rocks, calcium-free garnet cannot coexist with muscovite. Most of the mineral assemblages formed in the presence of excess quartz and muscovite. The phase-petrologic analysis, made with the aid of an eight-phase multisystematic model, shows the following major points: 1. Chloritoid and staurolite coexist in a definite interval of prograde metamorphism. 2. Biotite-chloritoid does not constitute an alternative assemblage to garnet-chlorite-muscovite, because the former combination is found predominantly in the presence of the latter combination. Because the garnet contains lime, all five phases are stable together in lowlime pelitic rocks. 3. The first appearance of staurolite in the area does not correspond to the reaction leading to the first intrinsic stable existence of this phase. Inasmuch as the first appearanc,e of staurolite is always in chlorite-bearing as semblages, I suggest that the mapped staurolite zone marker corresponds to a reaction whereby staurolitechlorite becomes stable. The probable lower grade chemical equivalent, for example, chloritoid-aluminum silicate, however, has not been found in the area of study. Several staurolite-forming reactions discussed in the literature are ruled out because of the relative siderophility of the minerals. A second staurolite isograd involves the reaction, chloritoid+chlorite+muscovite= staurolite+biotite. A third isograd involves staurolite+ chlorite=biotite+kyanite; this reaction is postulated on the basis of the observed assemblage biotite-kyanitesta urolite-garnet-muscoviteplagioclase-quartzilmenite. 4. In low-grade rocks, epidote is stable considerably before the first appearance of chloritoid. The nature of the high-aluminum phase in low-grade rocks that leads to the formation of chloritoid remains obscure. The epidote is always rich in ferric iron (pistacite content of about 1/ 4 to 1/3). Garnet-bearing assemblages (with or without epidote) are formed next as metamorphic grade increases. The next more calcium-rich silicate is hornblende, and despite the meager data on assemblages that include hornblende, the first intrinsic appearance of this phase has probably been recorded. At highstaurolite grade, the most calcium-rich assemblage in pelitic rocks is hornblende-garnet-biotite-plagioclase (bytownit

Densification of Zirconia with Borates.

DTIC Science & Technology

1980-01-24

solid electrolytes for fuel cell and oxygen sensor applications.1 ’ 2 The sintering temperatures for commercial quality stabilized zirconia powders are...in the temperature range 1450-1500C). A few studies were also made using a much coarser particle size (- 1-2 pm ave.) cubic stabilized zirconia ... powder , "Zircoa B" [Zirconia Corp. of America]. The additives used as sintering aids were reagent grade horic anhydride, calcium metaborate and calcium

Transcriptional Analysis of Aggressiveness and Heterogeneity across Grades of Astrocytomas

PubMed Central

Wang, Chunjing; Funk, Cory C.; Eddy, James A.; Price, Nathan D.

2013-01-01

Astrocytoma is the most common glioma, accounting for half of all primary brain and spinal cord tumors. Late detection and the aggressive nature of high-grade astrocytomas contribute to high mortality rates. Though many studies identify candidate biomarkers using high-throughput transcriptomic profiling to stratify grades and subtypes, few have resulted in clinically actionable results. This shortcoming can be attributed, in part, to pronounced lab effects that reduce signature robustness and varied individual gene expression among patients with the same tumor. We addressed these issues by uniformly preprocessing publicly available transcriptomic data, comprising 306 tumor samples from three astrocytoma grades (Grade 2, 3, and 4) and 30 non-tumor samples (normal brain as control tissues). Utilizing Differential Rank Conservation (DIRAC), a network-based classification approach, we examined the global and individual patterns of network regulation across tumor grades. Additionally, we applied gene-based approaches to identify genes whose expression changed consistently with increasing tumor grade and evaluated their robustness across multiple studies using statistical sampling. Applying DIRAC, we observed a global trend of greater network dysregulation with increasing tumor aggressiveness. Individual networks displaying greater differences in regulation between adjacent grades play well-known roles in calcium/PKC, EGF, and transcription signaling. Interestingly, many of the 90 individual genes found to monotonically increase or decrease with astrocytoma grade are implicated in cancer-affected processes such as calcium signaling, mitochondrial metabolism, and apoptosis. The fact that specific genes monotonically increase or decrease with increasing astrocytoma grade may reflect shared oncogenic mechanisms among phenotypically similar tumors. This work presents statistically significant results that enable better characterization of different human astrocytoma grades and hopefully can contribute towards improvements in diagnosis and therapy choices. Our results also identify a number of testable hypotheses relating to astrocytoma etiology that may prove helpful in developing much-needed biomarkers for earlier disease detection. PMID:24146911

Transcriptional analysis of aggressiveness and heterogeneity across grades of astrocytomas.

PubMed

Wang, Chunjing; Funk, Cory C; Eddy, James A; Price, Nathan D

2013-01-01

Astrocytoma is the most common glioma, accounting for half of all primary brain and spinal cord tumors. Late detection and the aggressive nature of high-grade astrocytomas contribute to high mortality rates. Though many studies identify candidate biomarkers using high-throughput transcriptomic profiling to stratify grades and subtypes, few have resulted in clinically actionable results. This shortcoming can be attributed, in part, to pronounced lab effects that reduce signature robustness and varied individual gene expression among patients with the same tumor. We addressed these issues by uniformly preprocessing publicly available transcriptomic data, comprising 306 tumor samples from three astrocytoma grades (Grade 2, 3, and 4) and 30 non-tumor samples (normal brain as control tissues). Utilizing Differential Rank Conservation (DIRAC), a network-based classification approach, we examined the global and individual patterns of network regulation across tumor grades. Additionally, we applied gene-based approaches to identify genes whose expression changed consistently with increasing tumor grade and evaluated their robustness across multiple studies using statistical sampling. Applying DIRAC, we observed a global trend of greater network dysregulation with increasing tumor aggressiveness. Individual networks displaying greater differences in regulation between adjacent grades play well-known roles in calcium/PKC, EGF, and transcription signaling. Interestingly, many of the 90 individual genes found to monotonically increase or decrease with astrocytoma grade are implicated in cancer-affected processes such as calcium signaling, mitochondrial metabolism, and apoptosis. The fact that specific genes monotonically increase or decrease with increasing astrocytoma grade may reflect shared oncogenic mechanisms among phenotypically similar tumors. This work presents statistically significant results that enable better characterization of different human astrocytoma grades and hopefully can contribute towards improvements in diagnosis and therapy choices. Our results also identify a number of testable hypotheses relating to astrocytoma etiology that may prove helpful in developing much-needed biomarkers for earlier disease detection.

The quantal nature of calcium release to caffeine in single smooth muscle cells results from activation of the sarcoplasmic reticulum Ca(2+)-ATPase.

PubMed

Steenbergen, J M; Fay, F S

1996-01-26

Calcium release from intracellular stores occurs in a graded manner in response to increasing concentrations of either inositol 1,4,5-trisphosphate or caffeine. To investigate the mechanism responsible for this quantal release phenomenon, [Ca2+] changes inside intracellular stores in isolated single smooth muscle cells were monitored with mag-fura 2. Following permeabilization with saponin or alpha-toxin the dye, loaded via its acetoxymethyl ester, was predominantly trapped in the sarcoplasmic reticulum (SR). Low caffeine concentrations in the absence of ATP induced only partial Ca2+ release; however, after inhibiting the calcium pump with thapsigargin the same stimulus released twice as much Ca2+. When the SR Ca(2+)-ATPase was rendered non-functional by depleting its "ATP pool," submaximal caffeine doses almost fully emptied the stores of Ca2+. We conclude that quantal release of Ca2+ in response to caffeine in these smooth muscle cells is largely due to the activity of the SR Ca(2+)-ATPase, which appears to return a portion of the released Ca2+ back to the SR, even in the absence of ATP. Apparently the SR Ca(2+)-ATPase is fueled by ATP, which is either compartmentalized or bound to the SR.

Lattice model for calcium dynamics

NASA Astrophysics Data System (ADS)

Guisoni, Nara; de Oliveira, Mario José

2005-06-01

We present a simplified lattice model to study calcium dynamics in the endoplasmic reticulum membrane. Calcium channels and calcium ions are placed in two interpenetrating square lattices which are connected in two ways: (i) via calcium release and (ii) because transitions between channel states are calcium dependent. The opening or closing of a channel is a stochastic process controlled by two functions which depend on the calcium density on the channel neighborhood. The model is studied through mean field calculations and simulations. We show that the critical behavior of the model changes drastically depending on the opening/closing functions. For certain choices of these functions, all channels are closed at very low and high calcium densities and the model presents one absorbing state.

Studying dyadic structure-function relationships: a review of current modeling approaches and new insights into Ca2+ (mis)handling.

PubMed

Maleckar, Mary M; Edwards, Andrew G; Louch, William E; Lines, Glenn T

2017-01-01

Excitation-contraction coupling in cardiac myocytes requires calcium influx through L-type calcium channels in the sarcolemma, which gates calcium release through sarcoplasmic reticulum ryanodine receptors in a process known as calcium-induced calcium release, producing a myoplasmic calcium transient and enabling cardiomyocyte contraction. The spatio-temporal dynamics of calcium release, buffering, and reuptake into the sarcoplasmic reticulum play a central role in excitation-contraction coupling in both normal and diseased cardiac myocytes. However, further quantitative understanding of these cells' calcium machinery and the study of mechanisms that underlie both normal cardiac function and calcium-dependent etiologies in heart disease requires accurate knowledge of cardiac ultrastructure, protein distribution and subcellular function. As current imaging techniques are limited in spatial resolution, limiting insight into changes in calcium handling, computational models of excitation-contraction coupling have been increasingly employed to probe these structure-function relationships. This review will focus on the development of structural models of cardiac calcium dynamics at the subcellular level, orienting the reader broadly towards the development of models of subcellular calcium handling in cardiomyocytes. Specific focus will be given to progress in recent years in terms of multi-scale modeling employing resolved spatial models of subcellular calcium machinery. A review of the state-of-the-art will be followed by a review of emergent insights into calcium-dependent etiologies in heart disease and, finally, we will offer a perspective on future directions for related computational modeling and simulation efforts.

TRP channels in calcium homeostasis: from hormonal control to structure-function relationship of TRPV5 and TRPV6.

PubMed

van Goor, Mark K C; Hoenderop, Joost G J; van der Wijst, Jenny

2017-06-01

Maintaining plasma calcium levels within a narrow range is of vital importance for many physiological functions. Therefore, calcium transport processes in the intestine, bone and kidney are tightly regulated to fine-tune the rate of absorption, storage and excretion. The TRPV5 and TRPV6 calcium channels are viewed as the gatekeepers of epithelial calcium transport. Several calciotropic hormones control the channels at the level of transcription, membrane expression, and function. Recent technological advances have provided the first near-atomic resolution structural models of several TRPV channels, allowing insight into their architecture. While this field is still in its infancy, it has increased our understanding of molecular channel regulation and holds great promise for future structure-function studies of these ion channels. This review will summarize the mechanisms that control the systemic calcium balance, as well as extrapolate structural views to the molecular functioning of TRPV5/6 channels in epithelial calcium transport. Copyright © 2016. Published by Elsevier B.V.

Calcium Hydroxylapatite Dermal Filler for Treatment of Dorsal Hand Volume Loss: Results From a 12-Month, Multicenter, Randomized, Blinded Trial.

PubMed

Goldman, Mitchel P; Moradi, Amir; Gold, Michael H; Friedmann, Daniel P; Alizadeh, Kaveh; Adelglass, Jeffrey M; Katz, Bruce E

2018-01-01

Calcium hydroxylapatite (CaHA) microspheres suspended in a carrier gel is an opaque dermal filler that has been used to provide immediate volume correction in the dorsal hands. To assess the safety and effectiveness of CaHA for the correction of volume loss in the hands up to 12 months. This multicenter, controlled, single-blind study (NCT01832090) included 114 subjects randomized 3:1 to CaHA treatment and untreated control groups. Effectiveness was assessed by blinded investigators using the validated Merz Hand Grading Scale (MHGS). Subject-reported improvement was assessed using the Global Aesthetic Improvement Scale. Effects of treatment on hand function were also assessed. A total of 75% of subjects achieved ≥1-point improvement on the MHGS (p < .0001) at 3 months (primary end point); this response was generally maintained through 12 months. Proportions of subjects reporting improvement ranged from 98% (3 months) to 86% (12 months). There were no clinically significant differences between control and CaHA-treated subjects in any hand function measure. Adverse events were generally expected, minor, short-lived, injection-related, and similar to those observed in previous CaHA clinical studies. Treatment with CaHA results in significant improvement in the appearance of the dorsal hand and is well tolerated.

Calcium and phosphorus supplementation of human milk for preterm infants.

PubMed

Harding, Jane E; Wilson, Jess; Brown, Julie

2017-02-26

Preterm infants are born with low skeletal stores of calcium and phosphorus. Preterm human milk provides insufficient calcium and phosphorus to meet the estimated needs of preterm infants for adequate growth. Supplementation of human milk with calcium and phosphorus may improve growth and development of preterm infants. To determine whether addition of calcium and phosphorus supplements to human milk leads to improved growth and bone metabolism of preterm infants without significant adverse effects. We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 3), MEDLINE via PubMed (1966 to 14 April 2016), Embase (1980 to 14 April 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 14 April 2016). We also searched clinical trials databases (11 May 2016) and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised and quasi-randomised trials comparing supplementation of human milk with calcium and/or phosphorus versus no supplementation in hospitalised preterm infants were eligible for inclusion in this review. Two review authors (JB, JW) independently extracted data and assessed trial quality using standard methods of the Cochrane Neonatal Review Group. We reported dichotomous data as risk ratios (RRs) and continuous data as mean differences (MDs) with 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence. This is an update of a 2001 review that identified no eligible trials. One trial including 40 infants met the inclusion criteria for this review. Using GRADE criteria, we judged the quality of the evidence as low owing to risk of bias (inadequate reporting of methods of randomisation, allocation concealment and/or blinding) and imprecision (wide confidence intervals and data from a single small trial). We found no evidence of a difference between calcium and phosphorus supplementation versus no supplementation for neonatal growth outcomes (weight, length, head circumference) at any time point reported (two, four or six weeks postnatal age). At six weeks postnatal age, supplementation with calcium/phosphorus was associated with a decrease in serum alkaline phosphatase concentration (MD -56.85 IU/L, 95% CI -101.27 to -12.43; one randomised controlled trial (RCT); n = 40 infants). Investigators provided no data on growth at 12 to 18 months, neonatal fractures, feed intolerance, breastfeeding or any of the prespecified childhood outcomes for this review (fractures, growth, neurodevelopmental outcomes). We identified one small trial including only 40 infants that compared supplementation of human milk with calcium and phosphorus versus no supplementation in hospitalised preterm infants. We judged the evidence to be of low quality and found no evidence of differences between groups for clinically important outcomes including growth and fractures. Although serum alkaline phosphatase concentration was reduced in the group receiving supplementation at six weeks postnatal age, this difference is unlikely to be of clinical significance. We conclude that evidence is insufficient to determine whether benefit or harm ensues when human milk is supplemented with calcium and/or phosphorus for the hospitalised preterm infant. We see no advantage of conducting further trials of this intervention because with the advent of multi-component human milk fortifier, supplementation of human milk with calcium and/or phosphorus alone is no longer common practice. Future trials should consider assessing effects of multi-component fortifiers with different mineral compositions on clinically important outcomes during the neonatal period and in later childhood.

The Plasma Membrane Calcium Pump

NASA Technical Reports Server (NTRS)

Rasmussen, H.

1983-01-01

Three aspect of cellular calcium metabolism in animal cells was discussed including the importance of the plasma membrane in calcium homeostasis, experiments dealing with the actual mechanism of the calcium pump, and the function of the pump in relationship to the mitochondria and to the function of calmodulin in the intact cell.

Acute intraoperative reactions during the injection of calcium sulfate bone cement for the treatment of unicameral bone cysts: a review of four cases.

PubMed

Nystrom, Lukas; Raw, Robert; Buckwalter, Joseph; Morcuende, Jose A

2008-01-01

Unicameral bone cysts can predispose patients to pathologic fracture and deformities of growth. Treatment options vary from continuous decompression with transcortical placement of a cannulated screw to percutaneous aspiration and injection of medical-grade calcium sulfate. From 2005 to 2007, we treated 22 patients with unicameral bone cysts using aspiration and injection of calcium sulfate. Three patients experienced acute laryngospasm and one patient developed tachyarrhythmia, temporarily, associated with injection of calcium sulfate. All reactions occurred in patients under age 18 without predisposing risk factors and resolved spontaneously with supportive care. Although the mechanism is unclear, we hypothesize that these reactions are either due to the nociceptive stimulus of the calcium sulfate injection or a systemic calcium bolus. Clinicians using this product for this indication should be aware that such reactions may occur. We suggest endotracheal intubation and communication to the anesthesiologist about the time of the injection in preparation for these idiopathic responses. Further research is necessary to determine exactly how this reaction occurs and how it can be avoided.

Acute Intraoperative Reactions During the Injection of Calcium Sulfate Bone Cement for the Treatment of Unicameral Bone Cysts: A Review of Four Cases

PubMed Central

Nystrom, Lukas; Raw, Robert; Buckwalter, Joseph; Morcuende, Jose A.

2008-01-01

Unicameral bone cysts can predispose patients to pathologic fracture and deformities of growth. Treatment options vary from continuous decompression with transcortical placement of a cannulated screw to percutaneous aspiration and injection of medical-grade calcium sulfate. From 2005 to 2007, we treated 22 patients with unicameral bone cysts using aspiration and injection of calcium sulfate. Three patients experienced acute laryngospasm and one patient developed tachyarrhythmia, temporarily, associated with injection of calcium sulfate. All reactions occurred in patients under age 18 without predisposing risk factors and resolved spontaneously with supportive care. Although the mechanism is unclear, we hypothesize that these reactions are either due to the nociceptive stimulus of the calcium sulfate injection or a systemic calcium bolus. Clinicians using this product for this indication should be aware that such reactions may occur. We suggest endotracheal intubation and communication to the anesthesiologist about the time of the injection in preparation for these idiopathic responses. Further research is necessary to determine exactly how this reaction occurs and how it can be avoided. PMID:19223954

One-Step Hydrothermal Synthesis of Zeolite X Powder from Natural Low-Grade Diatomite.

PubMed

Yao, Guangyuan; Lei, Jingjing; Zhang, Xiaoyu; Sun, Zhiming; Zheng, Shuilin

2018-05-28

Zeolite X powder was synthesized using natural low-grade diatomite as the main source of Si but only as a partial source of Al via a simple and green hydrothermal method. The microstructure and surface properties of the obtained samples were characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM), wavelength dispersive X-ray fluorescence (XRF), calcium ion exchange capacity (CEC), thermogravimetric-differential thermal (TG-DTA) analysis, and N₂ adsorption-desorption technique. The influence of various synthesis factors, including aging time and temperature, crystallization time and temperature, Na₂O/SiO₂ and H₂O/Na₂O ratio on the CEC of zeolite, were systematically investigated. The as-synthesized zeolite X with binary meso-microporous structure possessed remarkable thermal stability, high calcium ion exchange capacity of 248 mg/g and large surface area of 453 m²/g. In addition, the calcium ion exchange capacity of zeolite X was found to be mainly determined by the crystallization degree. In conclusion, the synthesized zeolite X using diatomite as a cost-effective raw material in this study has great potential for industrial application such as catalyst support and adsorbent.

A case of gain-of-function mutation in calcium-sensing receptor: supplemental hydration is required for renal protection.

PubMed

Suzuki, M; Aso, T; Sato, T; Michimata, M; Kazama, I; Saiki, H; Hatano, R; Ejima, Y; Miyama, N; Sato, A; Matsubara, M

2005-06-01

The calcium-sensing receptor (CaSR) regulates the extracellular calcium level, mainly by controlling parathyroid hormon secretion and renal calcium reabsorption. In gain-of-function CaSR mutations, the genetic abnormalities increase CaSR activity leading to the development of such clinical manifestations as hypercalciuric hypocalcemia and hypoparathyroidism. We report a Japanese case of CaSR gain-of-function mutation and represent a therapeutic intervention based on the functional characteristics of CaSR in renal tubule. DNA sequence analysis revealed a heterozygous G to T mutation identified in a 12-year-old Japanese girl presenting with sporadic onset of hypercalciuric hypocalcemia and hypoparathyroidism. The mutation is located in the N-terminal extracellular domain of the CaSR gene, one of the most important parts for the three-dimensional construction of the receptor, resulting in the substitution of phenylalanine for cysteine at amino acid 131 (C131F) in exon 3. Based on the diagnosis of the gain-of-function mutation in the CaSR, oral hydrochlorothiazide administration and supplemental hydration were started in addition to calcium supplementation. The combination therapy of thiazide and supplemental hydration markedly reduced both renal calcium excretion and urinary calcium concentration from 0.4-0.7 to less than 0.1 mg/mg (urinary calcium/creatinine ratio) and from 10-15 to 3-5 mg/dl (urinary calcium concentration), respectively. This therapy stopped the progression of renal calcification during the follow-up period. Supplemental hydration should be considered essential for the following reasons: (1) calcium supplementation activates the CaSR in the kidney and suppresses renal urinary concentrating ability, (2) the thiazide has a diuretic effect, (3) as calcium supplementation increases renal calcium excretion, the supplemental hydration decreases urinary calcium concentration by increasing urinary volume, thereby diminishing the risk of intratubular crystallization of calcium ion.

The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders

PubMed Central

Liao, Yajin; Dong, Yuan; Cheng, Jinbo

2017-01-01

The mitochondrial calcium uniporter (MCU)—a calcium uniporter on the inner membrane of mitochondria—controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP); however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure. In this review, we summarize the role of the MCU in controlling oxidative stress-elevated mitochondrial calcium and its function in neurodegenerative disorders. Inhibition of the MCU signaling pathway might be a new target for the treatment of neurodegenerative disorders. PMID:28208618

Effects of calcium on the incidence of recurrent colorectal adenomas

PubMed Central

Veettil, Sajesh K.; Ching, Siew Mooi; Lim, Kean Ghee; Saokaew, Surasak; Phisalprapa, Pochamana; Chaiyakunapruk, Nathorn

2017-01-01

Abstract Background: Protective effects of calcium supplementation against colorectal adenomas have been documented in systematic reviews; however, the results have not been conclusive. Our objective was to update and systematically evaluate the evidence for calcium supplementation taking into consideration the risks of systematic and random error and to GRADE the evidence. Methods: The study comprised a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized controlled trials (RCTs). We searched for RCTs published up until September 2016. Retrieved trials were evaluated using risk of bias. Primary outcome measures were the incidences of any recurrent adenomas and of advanced adenomas. Meta-analytic estimates were calculated with the random-effects model and random errors were evaluated with trial sequential analyses (TSAs). Results: Five randomized trials (2234 patients with a history of adenomas) were included. Two of the 5 trials showed either unclear or high risks of bias in most criteria. Meta-analysis of good quality RCTs suggest a moderate protective effect of calcium supplementation on recurrence of adenomas (relative risk [RR], 0.88 [95% CI 0.79–0.99]); however, its effects on advanced adenomas did not show statistical significance (RR, 1.02 [95% CI 0.67–1.55]). Subgroup analyses demonstrated a greater protective effect on recurrence of adenomas with elemental calcium dose ≥1600 mg/day (RR, 0.74 [95% CI 0.56–0.97]) compared to ≤1200 mg/day (RR, 0.84 [95% CI 0.73–0.97]). No major serious adverse events were associated with the use of calcium, but there was an increase in the incidence of hypercalcemia (P = .0095). TSA indicated a lack of firm evidence for a beneficial effect. Concerns with directness and imprecision rated down the quality of the evidence to “low.” Conclusion: The available good quality RCTs suggests a possible beneficial effect of calcium supplementation on the recurrence of adenomas; however, TSA indicated that the accumulated evidence is still inconclusive. Using GRADE-methodology, we conclude that the quality of evidence is low. Large well-designed randomized trials with low risk of bias are needed. PMID:28796047

High incidence of hypocalcemia and serum creatinine increase in patients with bone metastases treated with zoledronic acid.

PubMed

Zuradelli, Monica; Masci, Giovanna; Biancofiore, Giuseppe; Gullo, Giuseppe; Scorsetti, Marta; Navarria, Pierina; Tancioni, Flavio; Berlusconi, Marco; Giordano, Laura; Santoro, Armando

2009-05-01

Zoledronic acid belongs to the new generation of bisphosphonates with demonstrated clinical benefit for the treatment of bone metastases from different kinds of neoplasms. Hypocalcemia and serum creatinine elevation are expected adverse events during this therapy. The monitoring of serum calcium and creatinine is therefore recommended. The primary aim of this study was to establish the actual incidence of hypocalcemia and serum creatinine elevation during treatment with zoledronic acid. Skeletal-related events and side effects were also assessed. Serum creatinine and calcium levels were evaluated in 240 consecutive patients (83 males, 157 females; mean age, 62 years) with metastatic bone lesions from different solid tumors treated with zoledronic acid. Overall, 93 of 240 patients (38.8%) developed hypocalcemia, which was grade (G)1 in 45 patients (48.4%), G2 in 37 patients (39.8%), G3 in 10 patients (10.8%), and G4 in one patient (1.1%). The median time to occurrence of hypocalcemia (any grade) was 2.3 months after the beginning of the treatment (range, 0-34.9 months). Increased serum creatinine was observed in 33 of 240 patients (13.7%), of whom 19 had G1 (57.6%), 11 had G2 (33.3%), and three had G3 (9.1%). The median time to serum creatinine increase (for any grade) was 4.7 months (range, 0-29.2 months). Our analysis shows a high incidence of hypocalcemia and increased serum creatinine level during treatment with zoledronic acid. These results strongly support the need for accurate monitoring of plasma calcium and creatinine levels.

Restoration of parathyroid function after change of phosphate binder from calcium carbonate to lanthanum carbonate in hemodialysis patients with suppressed serum parathyroid hormone.

PubMed

Inaba, Masaaki; Okuno, Senji; Nagayama, Harumi; Yamada, Shinsuke; Ishimura, Eiji; Imanishi, Yasuo; Shoji, Shigeichi

2015-03-01

Control of phosphate is the most critical in the treatment of chronic kidney disease with mineral and bone disorder (CKD-MBD). Because calcium-containing phosphate binder to CKD patients is known to induce adynamic bone disease with ectopic calcification by increasing calcium load, we examined the effect of lanthanum carbonate (LaC), a non-calcium containing phosphate binder, to restore bone turnover in 27 hemodialysis patients with suppressed parathyroid function (serum intact parathyroid hormone [iPTH] ≦ 150 pg/mL). At the initiation of LaC administration, the dose of calcium-containing phosphate binder calcium carbonate (CaC) was withdrawn or reduced based on serum phosphate. After initiation of LaC administration, serum calcium and phosphate decreased significantly by 4 weeks, whereas whole PTH and iPTH increased. A significant and positive correlation between decreases of serum calcium, but not phosphate, with increases of whole PTH and iPTH, suggested that the decline in serum calcium with reduction of calcium load by LaC might increase parathyroid function. Serum bone resorption markers, such as serum tartrate-resistant acid phosphatase 5b, and N-telopeptide of type I collagen increased significantly by 4 weeks after LaC administration, which was followed by increases of serum bone formation markers including serum bone alkaline phosphatase, intact procollagen N-propeptide, and osteocalcin. Therefore, it was suggested that LaC attenuated CaC-induced suppression of parathyroid function and bone turnover by decreasing calcium load. In conclusion, replacement of CaC with LaC, either partially or totally, could increase parathyroid function and resultant bone turnover in hemodialysis patients with serum iPTH ≦ 150 pg/mL. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Calcium signaling in smooth muscle.

PubMed

Hill-Eubanks, David C; Werner, Matthias E; Heppner, Thomas J; Nelson, Mark T

2011-09-01

Changes in intracellular Ca(2+) are central to the function of smooth muscle, which lines the walls of all hollow organs. These changes take a variety of forms, from sustained, cell-wide increases to temporally varying, localized changes. The nature of the Ca(2+) signal is a reflection of the source of Ca(2+) (extracellular or intracellular) and the molecular entity responsible for generating it. Depending on the specific channel involved and the detection technology employed, extracellular Ca(2+) entry may be detected optically as graded elevations in intracellular Ca(2+), junctional Ca(2+) transients, Ca(2+) flashes, or Ca(2+) sparklets, whereas release of Ca(2+) from intracellular stores may manifest as Ca(2+) sparks, Ca(2+) puffs, or Ca(2+) waves. These diverse Ca(2+) signals collectively regulate a variety of functions. Some functions, such as contractility, are unique to smooth muscle; others are common to other excitable cells (e.g., modulation of membrane potential) and nonexcitable cells (e.g., regulation of gene expression).

PRESENILIN-NULL CELLS HAVE ALTERED TWO-PORE CALCIUM CHANNEL EXPRESSION AND LYSOSOMAL CALCIUM; IMPLICATIONS FOR LYSOSOMAL FUNCTION

PubMed Central

Kayala, Kara M Neely; Dickinson, George D; Minassian, Anet; Walls, Ken C; Green, Kim N; LaFerla, Frank M

2012-01-01

Presenilins are necessary for calcium homeostasis and also for efficient proteolysis through the autophagy/lysosome system. Presenilin regulates both endoplasmic reticulum calcium stores and autophagic proteolysis in a γ-secretase independent fashion. The endo-lysosome system can also act as a calcium store, with calcium efflux channels being recently identified as two-pore channels 1 and 2. Here we investigated lysosomal calcium content and the channels that mediate calcium release from these acidic stores in presenilin knockout cells. We report that presenilin loss leads to a lower total lysosomal calcium store despite the buildup of lysosomes found in these cells. Additionally, we find alterations in two-pore calcium channel protein expression, with loss of presenilin preventing the formation of a high molecular weight species of TPC1 and TPC2. Finally, we find that treatments that disturb lysosomal calcium release lead to a reduction in autophagy function yet lysosomal inhibitors do not alter two-pore calcium channel expression. These data indicate that alterations in lysosomal calcium in the absence of presenilins might be leading to disruptions in autophagy. PMID:23103503

The interplay of nanointerface curvature and calcium binding in weak polyelectrolyte-coated nanoparticles.

PubMed

Nap, Rikkert J; Gonzalez Solveyra, Estefania; Szleifer, Igal

2018-05-01

When engineering nanomaterials for application in biological systems, it is important to understand how multivalent ions, such as calcium, affect the structural and chemical properties of polymer-modified nanoconstructs. In this work, a recently developed molecular theory was employed to study the effect of surface curvature on the calcium-induced collapse of end-tethered weak polyelectrolytes. In particular, we focused on cylindrical and spherical nanoparticles coated with poly(acrylic acid) in the presence of different amounts of Ca2+ ions. We describe the structural changes that grafted polyelectrolytes undergo as a function of calcium concentration, surface curvature, and morphology. The polymer layers collapse in aqueous solutions that contain sufficient amounts of Ca2+ ions. This collapse, due to the formation of calcium bridges, is not only controlled by the calcium ion concentration but also strongly influenced by the curvature of the tethering surface. The transition from a swollen to a collapsed layer as a function of calcium concentration broadens and shifts to lower amounts of calcium ions as a function of the radius of cylindrical and spherical nanoparticles. The results show how the interplay between calcium binding and surface curvature governs the structural and functional properties of the polymer molecules. This would directly impact the fate of weak polyelectrolyte-coated nanoparticles in biological environments, in which calcium levels are tightly regulated. Understanding such interplay would also contribute to the rational design and optimization of smart interfaces with applications in, e.g., salt-sensitive and ion-responsive materials and devices.

Polynomial dual energy inverse functions for bone Calcium/Phosphorus ratio determination and experimental evaluation.

PubMed

Sotiropoulou, P; Fountos, G; Martini, N; Koukou, V; Michail, C; Kandarakis, I; Nikiforidis, G

2016-12-01

An X-ray dual energy (XRDE) method was examined, using polynomial nonlinear approximation of inverse functions for the determination of the bone Calcium-to-Phosphorus (Ca/P) mass ratio. Inverse fitting functions with the least-squares estimation were used, to determine calcium and phosphate thicknesses. The method was verified by measuring test bone phantoms with a dedicated dual energy system and compared with previously published dual energy data. The accuracy in the determination of the calcium and phosphate thicknesses improved with the polynomial nonlinear inverse function method, introduced in this work, (ranged from 1.4% to 6.2%), compared to the corresponding linear inverse function method (ranged from 1.4% to 19.5%). Copyright © 2016 Elsevier Ltd. All rights reserved.

Stack Gas Scrubber Makes the Grade

ERIC Educational Resources Information Center

Chemical and Engineering News, 1975

1975-01-01

Describes a year long test of successful sulfur dioxide removal from stack gas with a calcium oxide slurry. Sludge disposal problems are discussed. Cost is estimated at 0.6 mill per kwh not including sludge removal. A flow diagram and equations are included. (GH)

Graded Encoding of Food Odor Value in the Drosophila Brain

PubMed Central

Beshel, Jennifer

2013-01-01

Odors are highly evocative, yet how and where in the brain odors derive meaning remains unknown. Our analysis of the Drosophila brain extends the role of a small number of hunger-sensing neurons to include food-odor value representation. In vivo two-photon calcium imaging shows the amplitude of food odor-evoked activity in neurons expressing Drosophila neuropeptide F (dNPF), the neuropeptide Y homolog, strongly correlates with food-odor attractiveness. Hunger elevates neural and behavioral responses to food odors only, although food odors that elicit attraction in the fed state also evoke heightened dNPF activity in fed flies. Inactivation of a subset of dNPF-expressing neurons or silencing dNPF receptors abolishes food-odor attractiveness, whereas genetically enhanced dNPF activity not only increases food-odor attractiveness but promotes attraction to aversive odors. Varying the amount of presented odor produces matching graded neural and behavioral curves, which can function to predict preference between odors. We thus demonstrate a possible motivationally scaled neural “value signal” accessible from uniquely identifiable cells. PMID:24089477

Best time window for the use of calcium-modulating agents to improve functional recovery in injured peripheral nerves-An experiment in rats.

PubMed

Yan, Yuhui; Shen, Feng-Yi; Agresti, Michael; Zhang, Lin-Ling; Matloub, Hani S; LoGiudice, John A; Havlik, Robert; Li, Jifeng; Gu, Yu-Dong; Yan, Ji-Geng

2017-09-01

Peripheral nerve injury can have a devastating effect on daily life. Calcium concentrations in nerve fibers drastically increase after nerve injury, and this activates downstream processes leading to neuron death. Our previous studies showed that calcium-modulating agents decrease calcium accumulation, which aids in regeneration of injured peripheral nerves; however, the optimal therapeutic window for this application has not yet been identified. In this study, we show that calcium clearance after nerve injury is positively correlated with functional recovery in rats suffering from a crushed sciatic nerve injury. After the nerve injury, calcium accumulation increased. Peak volume is from 2 to 8 weeks post injury; calcium accumulation then gradually decreased over the following 24-week period. The compound muscle action potential (CMAP) measurement from the extensor digitorum longus muscle recovered to nearly normal levels in 24 weeks. Simultaneously, real-time polymerase chain reaction results showed that upregulation of calcium-ATPase (a membrane protein that transports calcium out of nerve fibers) mRNA peaked at 12 weeks. These results suggest that without intervention, the peak in calcium-ATPase mRNA expression in the injured nerve occurs after the peak in calcium accumulation, and CMAP recovery continues beyond 24 weeks. Immediately using calcium-modulating agents after crushed nerve injury improved functional recovery. These studies suggest that a crucial time frame in which to initiate effective clinical approaches to accelerate calcium clearance and nerve regeneration would be prior to 2 weeks post injury. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Dynamic changes in neural circuit topology following mild mechanical injury in vitro.

PubMed

Patel, Tapan P; Ventre, Scott C; Meaney, David F

2012-01-01

Despite its enormous incidence, mild traumatic brain injury is not well understood. One aspect that needs more definition is how the mechanical energy during injury affects neural circuit function. Recent developments in cellular imaging probes provide an opportunity to assess the dynamic state of neural networks with single-cell resolution. In this article, we developed imaging methods to assess the state of dissociated cortical networks exposed to mild injury. We estimated the imaging conditions needed to achieve accurate measures of network properties, and applied these methodologies to evaluate if mild mechanical injury to cortical neurons produces graded changes to either spontaneous network activity or altered network topology. We found that modest injury produced a transient increase in calcium activity that dissipated within 1 h after injury. Alternatively, moderate mechanical injury produced immediate disruption in network synchrony, loss in excitatory tone, and increased modular topology. A calcium-activated neutral protease (calpain) was a key intermediary in these changes; blocking calpain activation restored the network nearly completely to its pre-injury state. Together, these findings show a more complex change in neural circuit behavior than previously reported for mild mechanical injury, and highlight at least one important early mechanism responsible for these changes.

Calcium Phosphate Bioceramics: A Review of Their History, Structure, Properties, Coating Technologies and Biomedical Applications.

PubMed

Eliaz, Noam; Metoki, Noah

2017-03-24

Calcium phosphate (CaP) bioceramics are widely used in the field of bone regeneration, both in orthopedics and in dentistry, due to their good biocompatibility, osseointegration and osteoconduction. The aim of this article is to review the history, structure, properties and clinical applications of these materials, whether they are in the form of bone cements, paste, scaffolds, or coatings. Major analytical techniques for characterization of CaPs, in vitro and in vivo tests, and the requirements of the US Food and Drug Administration (FDA) and international standards from CaP coatings on orthopedic and dental endosseous implants, are also summarized, along with the possible effect of sterilization on these materials. CaP coating technologies are summarized, with a focus on electrochemical processes. Theories on the formation of transient precursor phases in biomineralization, the dissolution and reprecipitation as bone of CaPs are discussed. A wide variety of CaPs are presented, from the individual phases to nano-CaP, biphasic and triphasic CaP formulations, composite CaP coatings and cements, functionally graded materials (FGMs), and antibacterial CaPs. We conclude by foreseeing the future of CaPs.

Calcium Phosphate Bioceramics: A Review of Their History, Structure, Properties, Coating Technologies and Biomedical Applications

PubMed Central

Eliaz, Noam; Metoki, Noah

2017-01-01

Calcium phosphate (CaP) bioceramics are widely used in the field of bone regeneration, both in orthopedics and in dentistry, due to their good biocompatibility, osseointegration and osteoconduction. The aim of this article is to review the history, structure, properties and clinical applications of these materials, whether they are in the form of bone cements, paste, scaffolds, or coatings. Major analytical techniques for characterization of CaPs, in vitro and in vivo tests, and the requirements of the US Food and Drug Administration (FDA) and international standards from CaP coatings on orthopedic and dental endosseous implants, are also summarized, along with the possible effect of sterilization on these materials. CaP coating technologies are summarized, with a focus on electrochemical processes. Theories on the formation of transient precursor phases in biomineralization, the dissolution and reprecipitation as bone of CaPs are discussed. A wide variety of CaPs are presented, from the individual phases to nano-CaP, biphasic and triphasic CaP formulations, composite CaP coatings and cements, functionally graded materials (FGMs), and antibacterial CaPs. We conclude by foreseeing the future of CaPs. PMID:28772697

Ultracytochemical visualization of calcium distribution in heart cells and erythrocytes of zebrafish Danio rerio.

PubMed

Niksirat, Hamid; Steinbach, Christoph

2018-05-24

Detection of patterns of subcellular calcium distribution in the cardiovascular system can contribute to understanding its role in cardiac and blood function. The present study localized calcium in heart atrium, ventricle, and bulbus arteriosus as well as in erythrocytes of zebrafish Danio rerio using an oxalate-pyroantimonate technique combined with transmission electron microscopy. Intracellular calcium stores were detected in caveolae, mitochondria, and the nuclei of several zebrafish cardiac cell types. Melanin pigmentation containing calcium stores was detected in the pericardial cavity. Melanin might be an extracellular source of calcium for heart beating and/or a lubricant to prevent friction during beating process. Calcium deposits were also detected in the plasma membrane, cytoplasm and nucleus of erythrocytes as well as in blood plasma. Possible exchange of calcium between erythrocytes and blood plasma was observed. Interactions of such calcium stores and possible contribution of extracellular calcium stores such as melanin pigmentation to supply calcium for vital functions of heart cells should be addressed in future studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Arterial Smooth Muscle Mitochondria Amplify Hydrogen Peroxide Microdomains Functionally Coupled to L-Type Calcium Channels

PubMed Central

Chaplin, Nathan L.; Nieves-Cintrón, Madeline; Fresquez, Adriana M.; Navedo, Manuel F.; Amberg, Gregory C.

2015-01-01

Rationale Mitochondria are key integrators of convergent intracellular signaling pathways. Two important second messengers modulated by mitochondria are calcium and reactive oxygen species. To date, coherent mechanisms describing mitochondrial integration of calcium and oxidative signaling in arterial smooth muscle are incomplete. Objective To address and add clarity to this issue we tested the hypothesis that mitochondria regulate subplasmalemmal calcium and hydrogen peroxide microdomain signaling in cerebral arterial smooth muscle. Methods and Results Using an image-based approach we investigated the impact of mitochondrial regulation of L-type calcium channels on subcellular calcium and ROS signaling microdomains in isolated arterial smooth muscle cells. Our single cell observations were then related experimentally to intact arterial segments and to living animals. We found that subplasmalemmal mitochondrial amplification of hydrogen peroxide microdomain signaling stimulates L-type calcium channels and that this mechanism strongly impacts the functional capacity of the vasoconstrictor angiotensin II. Importantly, we also found that disrupting this mitochondrial amplification mechanism in vivo normalized arterial function and attenuated the hypertensive response to systemic endothelial dysfunction. Conclusions From these observations we conclude that mitochondrial amplification of subplasmalemmal calcium and hydrogen peroxide microdomain signaling is a fundamental mechanism regulating arterial smooth muscle function. As the principle components involved are fairly ubiquitous and positioning of mitochondria near the plasma membrane is not restricted to arterial smooth muscle, this mechanism could occur in many cell types and contribute to pathological elevations of intracellular calcium and increased oxidative stress associated with many diseases. PMID:26390880

The high prevalence of pathologic calcium crystals in pre-operative knees.

PubMed

Derfus, Beth A; Kurian, Jason B; Butler, Jeffrey J; Daft, Laureen J; Carrera, Guillermo F; Ryan, Lawrence M; Rosenthal, Ann K

2002-03-01

Calcium pyrophosphate dihydrate (CPPD) and basic calcium phosphate (BCP) crystals are important in the pathogenesis of osteoarthritis (OA) but are under recognized even in end stage disease. We determined the prevalence of these calcium crystals in synovial fluid (SF) of persons undergoing total knee arthroplasty for degenerative arthritis. SF samples were obtained from 53 knee joints undergoing total arthroplasty for a pre-operative diagnosis of OA. SF were analyzed via compensated light microscopy for CPPD crystals and a semiquantitative radiometric assay for BCP crystals. Fifty pre-operative radiographs were analyzed and graded according to the scale of Kellgren and Lawrence. Patients had an average age of 70 years at the time of surgery. CPPD and/or BCP crystals were identified in 60% of SF. Overall radiographic scores correlated with mean concentrations of BCP crystals. Higher mean radiographic scores correlated with the presence of calcium-containing crystals of either type in SF Radiographic chondrocalcinosis was identified in only 31% of those with SF CPPD. Pathologic calcium crystals were present in a majority of SF at the time of total knee arthroplasty. Intraoperative SF analysis could conveniently identify pathologic calcium crystals providing information that may be relevant to the future care of the patient's replaced joint and that of other joints. This information could also potentially aid in predicting the likelihood of the need for contralateral total knee arthroplasty.

Cardiac voltage gated calcium channels and their regulation by β-adrenergic signaling.

PubMed

Kumari, Neema; Gaur, Himanshu; Bhargava, Anamika

2018-02-01

Voltage-gated calcium channels (VGCCs) are the predominant source of calcium influx in the heart leading to calcium-induced calcium release and ultimately excitation-contraction coupling. In the heart, VGCCs are modulated by the β-adrenergic signaling. Signaling through β-adrenergic receptors (βARs) and modulation of VGCCs by β-adrenergic signaling in the heart are critical signaling and changes to these have been significantly implicated in heart failure. However, data related to calcium channel dysfunction in heart failure is divergent and contradictory ranging from reduced function to no change in the calcium current. Many recent studies have highlighted the importance of functional and spatial microdomains in the heart and that may be the key to answer several puzzling questions. In this review, we have briefly discussed the types of VGCCs found in heart tissues, their structure, and significance in the normal and pathological condition of the heart. More importantly, we have reviewed the modulation of VGCCs by βARs in normal and pathological conditions incorporating functional and structural aspects. There are different types of βARs, each having their own significance in the functioning of the heart. Finally, we emphasize the importance of location of proteins as it relates to their function and modulation by co-signaling molecules. Its implication on the studies of heart failure is speculated. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of chelators on functionality of milk protein concentrates obtained by ultrafiltration at a constant pH and temperature.

PubMed

Ramchandran, Lata; Luo, XiaoXia; Vasiljevic, Todor

2017-11-01

Modulating conditions during ultrafiltration of skim milk appears to be a feasible strategy to obtain milk protein concentrates (MPC) with tailored functionalities. Adjustment of pH and process temperature attenuated properties of casein micelle resulting in enhanced emulsification capacity. Additional pre-treatment options such as addition of calcium chelators can further impact on the functionality of MPC by modifying the calcium distribution and casein micelle integrity. The objective of the project was to establish effects of pre-treating skim milk with calcium chelators (EDTA or citrate) in concentrations between 10 to 30 mm prior to UF on the physical properties of the feed, corresponding retentates and dried MPC, including particle size, zeta potential and calcium distribution in skim milk and the corresponding retentates, as well as the physical functionalities such as solubility, heat stability and emulsifying properties. Addition of calcium chelators (EDTA or citrate), at levels 20-30 mm concentrations reduced casein micelle size as well as total, soluble and ionic calcium contents that resulted in MPC with enhanced solubility and heat stability. The emulsion capacity was, however, improved only with EDTA at 10 mm concentration. The enhanced functionality is attributed to the reduced particle size resulting from the removal of calcium from the retentate that could modify micellar casein to an extent sufficient to cause such improvements.

Calcium Pumps and Interacting BON1 Protein Modulate Calcium Signature, Stomatal Closure, and Plant Immunity1[OPEN

PubMed Central

Bao, Yongmei; Yang, Ziyuan; Yu, Huiyun; Li, Yun; Wang, Shu; Zou, Baohong; Xu, Dachao; Ma, Zhiqi

2017-01-01

Calcium signaling is essential for environmental responses including immune responses. Here, we provide evidence that the evolutionarily conserved protein BONZAI1 (BON1) functions together with autoinhibited calcium ATPase10 (ACA10) and ACA8 to regulate calcium signals in Arabidopsis. BON1 is a plasma membrane localized protein that negatively regulates the expression of immune receptor genes and positively regulates stomatal closure. We found that BON1 interacts with the autoinhibitory domains of ACA10 and ACA8, and the aca10 loss-of-function (LOF) mutants have an autoimmune phenotype similar to that of the bon1 LOF mutants. Genetic evidences indicate that BON1 positively regulates the activities of ACA10 and ACA8. Consistent with this idea, the steady level of calcium concentration is increased in both aca10 and bon1 mutants. Most strikingly, cytosolic calcium oscillation imposed by external calcium treatment was altered in aca10, aca8, and bon1 mutants in guard cells. In addition, calcium- and pathogen-induced stomatal closure was compromised in the aca10 and bon1 mutants. Taken together, this study indicates that ACA10/8 and BON1 physically interact on plasma membrane and function in the generation of cytosol calcium signatures that are critical for stomatal movement and impact plant immunity. PMID:28701352

Apo states of calmodulin and CaBP1 control CaV1 voltage-gated calcium channel function through direct competition for the IQ domain.

PubMed

Findeisen, Felix; Rumpf, Christine H; Minor, Daniel L

2013-09-09

In neurons, binding of calmodulin (CaM) or calcium-binding protein 1 (CaBP1) to the CaV1 (L-type) voltage-gated calcium channel IQ domain endows the channel with diametrically opposed properties. CaM causes calcium-dependent inactivation and limits calcium entry, whereas CaBP1 blocks calcium-dependent inactivation (CDI) and allows sustained calcium influx. Here, we combine isothermal titration calorimetry with cell-based functional measurements and mathematical modeling to show that these calcium sensors behave in a competitive manner that is explained quantitatively by their apo-state binding affinities for the IQ domain. This competition can be completely blocked by covalent tethering of CaM to the channel. Further, we show that Ca(2+)/CaM has a sub-picomolar affinity for the IQ domain that is achieved without drastic alteration of calcium-binding properties. The observation that the apo forms of CaM and CaBP1 compete with each other demonstrates a simple mechanism for direct modulation of CaV1 function and suggests a means by which excitable cells may dynamically tune CaV activity. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparative Effectiveness of Phosphate Binders in Patients with Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis.

PubMed

Sekercioglu, Nigar; Thabane, Lehana; Díaz Martínez, Juan Pablo; Nesrallah, Gihad; Longo, Christopher J; Busse, Jason W; Akhtar-Danesh, Noori; Agarwal, Arnav; Al-Khalifah, Reem; Iorio, Alfonso; Guyatt, Gordon H

2016-01-01

Chronic kidney disease-mineral and bone disorder (CKD-MBD) has been linked to poor health outcomes, including diminished quality and length of life. This condition is characterized by high phosphate levels and requires phosphate-lowering agents-phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on patient-important outcomes in patients with CKD-MBD. Data sources included MEDLINE and EMBASE Trials from 1996 to February 2016. We also searched the Cochrane Register of Controlled Trials up to April 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible randomized controlled trials (RCTs). Eligible trials enrolled patients with CKD-MBD, randomized them to receive calcium (delivered as calcium acetate, calcium citrate or calcium carbonate), non-calcium-based phosphate binders (NCBPB) (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide and ferric citrate), phosphorus restricted diet, placebo or no treatment, and reported effects on all-cause mortality, cardiovascular mortality or hospitalization at ≥4 weeks follow-up. We performed network meta-analyses (NMA) for all cause-mortality for individual agents (seven-node analysis) and conventional meta-analysis of calcium vs. NCBPBs for all-cause mortality, cardiovascular mortality and hospitalization. In the NMAs, we calculated the effect estimates for direct, indirect and network meta-analysis estimates; for both NMA and conventional meta-analysis, we pooled treatment effects as risk ratios (RR) and calculated 95% confidence intervals (CIs) using random effect models. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for each paired comparison. Our search yielded 1190 citations, of which 71 RCTs were retrieved for full review and 15 proved eligible. With 13 eligible studies from a prior review, we included 28 studies with 8335 participants; 25 trials provided data for our quantitative synthesis. Results suggest higher mortality with calcium than either sevelamer (NMA RR, 1.89 [95% CI, 1.02 to 3.50], moderate quality evidence) or NCBPBs (conventional meta-analysis RR, 1.76 [95% CI, 1.21 to 2.56, moderate quality evidence). Conventional meta-analysis suggested no difference in cardiovascular mortality between calcium and NCBPBs (RR, 2.54 [95% CI, 0.67 to 9.62 low quality evidence). Our results suggest higher hospitalization, although non-significant, with calcium than NCBPBs (RR, 1.293 [95% CI, 0.94 to 1.74, moderate quality evidence). Use of calcium results in higher mortality than either sevelamer in particular and NCBPBs in general (moderate quality evidence). Our results raise questions about whether administration of calcium as an intervention for CKD- MBD remains ethical. Further research is needed to explore the effects of different types of phosphate binders, including novel agents such as iron, on quality and quantity of life. PROSPERO CRD-42016032945.

Apo-states of calmodulin and CaBP1 control CaV1 voltage-gated calcium channel function through direct competition for the IQ domain

PubMed Central

Findeisen, Felix; Rumpf, Christine; Minor, Daniel L.

2013-01-01

In neurons, binding of calmodulin (CaM) or calcium-binding protein 1 (CaBP1) to the CaV1 (L-type) voltage-gated calcium channel IQ domain endows the channel with diametrically opposed properties. CaM causes calcium-dependent inactivation (CDI) and limits calcium entry, whereas CaBP1 blocks CDI and allows sustained calcium influx. Here, we combine isothermal titration calorimetry (ITC) with cell-based functional measurements and mathematical modeling to show that these calcium sensors behave in a competitive manner that is explained quantitatively by their apo-state binding affinities for the IQ domain. This competition can be completely blocked by covalent tethering of CaM to the channel. Further, we show that Ca2+/CaM has a sub-picomolar affinity for the IQ domain that is achieved without drastic alteration of calcium binding properties. The observation that the apo-forms of CaM and CaBP1 compete with each other demonstrates a simple mechanism for direct modulation of CaV1 function and suggests a means by which excitable cells may dynamically tune CaV activity. PMID:23811053

Calcium as a cardiovascular toxin in CKD-MBD.

PubMed

Moe, Sharon M

2017-07-01

Disordered calcium balance and homeostasis are common in patients with chronic kidney disease. Such alterations are commonly associated with abnormal bone remodeling, directly and indirectly. Similarly, positive calcium balance may also be a factor in the pathogenesis of extra skeletal soft tissue and arterial calcification. Calcium may directly affect cardiac structure and function through direct effects to alter cell signaling due to abnormal intracellular calcium homeostasis 2) extra-skeletal deposition of calcium and phosphate in the myocardium and small cardiac arterioles, 3) inducing cardiomyocyte hypertrophy through calcium and hormone activation of NFAT signaling mechanisms, and 4) increased aorta calcification resulting in chronic increased afterload leading to hypertrophy. Similarly, calcium may alter vascular smooth muscle cell function and affect cell signaling which may predispose to a proliferative phenotype important in arteriosclerosis and arterial calcification. Thus, disorders of calcium balance and homeostasis due to CKD-MBD may play a role in the high cardiovascular burden observed in patients with CKD. Published by Elsevier Inc.

Regulation of Cellular Calcium in Vestibular Supporting Cells by Otopetrin 1

PubMed Central

Kim, Euysoo; Hyrc, Krzysztof L.; Speck, Judith; Lundberg, Yunxia W.; Salles, Felipe T.; Kachar, Bechara; Goldberg, Mark P.; Warchol, Mark E.

2010-01-01

Otopetrin 1 (OTOP1) is a multitransmembrane domain protein, which is essential for mineralization of otoconia, the calcium carbonate biominerals required for vestibular function, and the normal sensation of gravity. The mechanism driving mineralization of otoconia is poorly understood, but it has been proposed that supporting cells and a mechanism to maintain high concentrations of calcium are critical. Using Otop1 knockout mice and a utricular epithelial organ culture system, we show that OTOP1 is expressed at the apex of supporting cells and functions to increase cytosolic calcium in response to purinergic agonists, such as adenosine 5′-triphosphate (ATP). This is achieved by blocking mobilization of calcium from intracellular stores in an extracellular calcium-dependent manner and by mediating influx of extracellular calcium. These data support a model in which OTOP1 acts as a sensor of the extracellular calcium concentration near supporting cells and responds to ATP in the endolymph to increase intracellular calcium levels during otoconia mineralization. PMID:20554841

Association of conjunctival and corneal calcification with vascular calcification among hepatitis-C-seropositive hemodialysis patients.

PubMed

AbouSeif, Khaled; Sany, Dawlat; Elshahawy, Yasser; Seddik, Ayman; Rahman, Khedr; Gaber, Moustapha

2016-01-01

Disorders associated with the hepatitis C virus (HCV) have been reported including cardiovascular, metabolic, and central nervous system diseases. Since chronic HCV infections may be curable, their identification as causal contributors to cardiovascular risk could offer new perspectives in the prevention of cardiovascular disease. The aim of this study is to investigate the association between HCV and aortic arch calcification (AAC) and corneal and conjunctival calcification (CCC) in maintenance hemodialysis (MHD) patients; further, we assessed the correlation of CCC with vascular calcification. A total of 100 patients undergoing hemodialysis (HD) in our hospital were included in this study. Patients underwent a complete ocular examination including intraocular pressure, and CCC was looked for by slit lamp and fundoscopy. CCC was graded according to modified Porter and Crombie classification system described by Tokuyama et al. Helical computerized tomographic chest examination was used to evaluate the grading of AAC. Demographic, hematological, biochemical, and dialysis-related data were obtained. There was significant difference between seropositive (n = 51) and seronegative patients (n = 49) regarding grading of AAC and CCC (P <0.001). Significant positive correlation was found between grading of CCC, AAC, age (P <0.001), duration on HD (P <0.001), HCV-antibody positivity (P <0.001), serum calcium level (P <0.001), serum phosphorus level (P <0.001), calcium × phosphorus product (P <0.001), and i-parathormone level (P < 0.001). In addition, CCC grading positively correlated with AAC. Our results suggest that patients undergoing HD infected with the HCV have high degree of CCC, AAC, and mineral metabolism disorder. The strong correlation between CCC and AAC indicates that CCC evaluation is an easy, fast, non-invasive method, and might be used as an indirect indicator to detect vascular calcification in patients undergoing MHD.

Calcium Imaging of AM Dyes Following Prolonged Incubation in Acute Neuronal Tissue

PubMed Central

Morley, John W.; Tapson, Jonathan; Breen, Paul P.; van Schaik, André

2016-01-01

Calcium-imaging is a sensitive method for monitoring calcium dynamics during neuronal activity. As intracellular calcium concentration is correlated to physiological and pathophysiological activity of neurons, calcium imaging with fluorescent indicators is one of the most commonly used techniques in neuroscience today. Current methodologies for loading calcium dyes into the tissue require prolonged incubation time (45–150 min), in addition to dissection and recovery time after the slicing procedure. This prolonged incubation curtails experimental time, as tissue is typically maintained for 6–8 hours after slicing. Using a recently introduced recovery chamber that extends the viability of acute brain slices to more than 24 hours, we tested the effectiveness of calcium AM staining following long incubation periods post cell loading and its impact on the functional properties of calcium signals in acute brain slices and wholemount retinae. We show that calcium dyes remain within cells and are fully functional >24 hours after loading. Moreover, the calcium dynamics recorded >24 hrs were similar to the calcium signals recorded in fresh tissue that was incubated for <4 hrs. These results indicate that long exposure of calcium AM dyes to the intracellular cytoplasm did not alter the intracellular calcium concentration, the functional range of the dye or viability of the neurons. This data extends our previous work showing that a custom recovery chamber can extend the viability of neuronal tissue, and reliable data for both electrophysiology and imaging can be obtained >24hrs after dissection. These methods will not only extend experimental time for those using acute neuronal tissue, but also may reduce the number of animals required to complete experimental goals. PMID:27183102

Why Calcium? How Calcium Became the Best Communicator*

PubMed Central

Carafoli, Ernesto; Krebs, Joachim

2016-01-01

Calcium carries messages to virtually all important functions of cells. Although it was already active in unicellular organisms, its role became universally important after the transition to multicellular life. In this Minireview, we explore how calcium ended up in this privileged position. Most likely its unique coordination chemistry was a decisive factor as it makes its binding by complex molecules particularly easy even in the presence of large excesses of other cations, e.g. magnesium. Its free concentration within cells can thus be maintained at the very low levels demanded by the signaling function. A large cadre of proteins has evolved to bind or transport calcium. They all contribute to buffer it within cells, but a number of them also decode its message for the benefit of the target. The most important of these “calcium sensors” are the EF-hand proteins. Calcium is an ambivalent messenger. Although essential to the correct functioning of cell processes, if not carefully controlled spatially and temporally within cells, it generates variously severe cell dysfunctions, and even cell death. PMID:27462077

Why Calcium? How Calcium Became the Best Communicator.

PubMed

Carafoli, Ernesto; Krebs, Joachim

2016-09-30

Calcium carries messages to virtually all important functions of cells. Although it was already active in unicellular organisms, its role became universally important after the transition to multicellular life. In this Minireview, we explore how calcium ended up in this privileged position. Most likely its unique coordination chemistry was a decisive factor as it makes its binding by complex molecules particularly easy even in the presence of large excesses of other cations, e.g. magnesium. Its free concentration within cells can thus be maintained at the very low levels demanded by the signaling function. A large cadre of proteins has evolved to bind or transport calcium. They all contribute to buffer it within cells, but a number of them also decode its message for the benefit of the target. The most important of these "calcium sensors" are the EF-hand proteins. Calcium is an ambivalent messenger. Although essential to the correct functioning of cell processes, if not carefully controlled spatially and temporally within cells, it generates variously severe cell dysfunctions, and even cell death. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Muscle mitochondrial metabolism and calcium signaling impairment in patients treated with statins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sirvent, P., E-mail: pascal.sirvent@univ-bpclermont.fr; CHRU Montpellier, 34295 Montpellier; Clermont Université, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en conditions Physiologiques et Pathologiques

2012-03-01

The most common and problematic side effect of statins is myopathy. To date, the patho-physiological mechanisms of statin myotoxicity are still not clearly understood. In previous studies, we showed that acute application in vitro of simvastatin caused impairment of mitochondrial function and dysfunction of calcium homeostasis in human and rat healthy muscle samples. We thus evaluated in the present study, mitochondrial function and calcium signaling in muscles of patients treated with statins, who present or not muscle symptoms, by oxygraphy and recording of calcium sparks, respectively. Patients treated with statins showed impairment of mitochondrial respiration that involved mainly the complexmore » I of the respiratory chain and altered frequency and amplitude of calcium sparks. The muscle problems observed in statin-treated patients appear thus to be related to impairment of mitochondrial function and muscle calcium homeostasis, confirming the results we previously reported in vitro. -- Highlights: ► The most common and problematic side effect of statins is myopathy. ► Patients treated with statins showed impairment of mitochondrial respiration. ► Statins-treated patients showed altered frequency and amplitude of calcium sparks.« less

Live Imaging of Calcium Dynamics during Axon Degeneration Reveals Two Functionally Distinct Phases of Calcium Influx

PubMed Central

Yamagishi, Yuya; Tessier-Lavigne, Marc

2015-01-01

Calcium is a key regulator of axon degeneration caused by trauma and disease, but its specific spatial and temporal dynamics in injured axons remain unclear. To clarify the function of calcium in axon degeneration, we observed calcium dynamics in single injured neurons in live zebrafish larvae and tested the temporal requirement for calcium in zebrafish neurons and cultured mouse DRG neurons. Using laser axotomy to induce Wallerian degeneration (WD) in zebrafish peripheral sensory axons, we monitored calcium dynamics from injury to fragmentation, revealing two stereotyped phases of axonal calcium influx. First, axotomy triggered a transient local calcium wave originating at the injury site. This initial calcium wave only disrupted mitochondria near the injury site and was not altered by expression of the protective WD slow (WldS) protein. Inducing multiple waves with additional axotomies did not change the kinetics of degeneration. In contrast, a second phase of calcium influx occurring minutes before fragmentation spread as a wave throughout the axon, entered mitochondria, and was abolished by WldS expression. In live zebrafish, chelating calcium after the first wave, but before the second wave, delayed the progress of fragmentation. In cultured DRG neurons, chelating calcium early in the process of WD did not alter degeneration, but chelating calcium late in WD delayed fragmentation. We propose that a terminal calcium wave is a key instructive component of the axon degeneration program. SIGNIFICANCE STATEMENT Axon degeneration resulting from trauma or neurodegenerative disease can cause devastating deficits in neural function. Understanding the molecular and cellular events that execute axon degeneration is essential for developing treatments to address these conditions. Calcium is known to contribute to axon degeneration, but its temporal requirements in this process have been unclear. Live calcium imaging in severed zebrafish neurons and temporally controlled pharmacological treatments in both zebrafish and cultured mouse sensory neurons revealed that axonal calcium influx late in the degeneration process regulates axon fragmentation. These findings suggest that temporal considerations will be crucial for developing treatments for diseases associated with axon degeneration. PMID:26558774

Hypoparathyroidism

MedlinePlus

... and slow mental development. Too much treatment with vitamin D and calcium can cause high blood calcium ( hypercalcemia ) or high urine calcium (hypercalciuria). Excess treatment may sometimes interfere with kidney function, or ...

Functionally heterogenous ryanodine receptors in avian cerebellum.

PubMed

Sierralta, J; Fill, M; Suárez-Isla, B A

1996-07-19

The functional heterogeneity of the ryanodine receptor (RyR) channels in avian cerebellum was defined. Heavy endoplasmic reticulum microsomes had significant levels of ryanodine and inositol 1,4,5-trisphosphate binding. Scatchard analysis and kinetic studies indicated the existence of at least two distinct ryanodine binding sites. Ryanodine binding was calcium-dependent but was not significantly enhanced by caffeine. Incorporation of microsomes into planar lipid bilayers revealed ion channels with pharmacological features (calcium, magnesium, ATP, and caffeine sensitivity) similar to the RyR channels found in mammalian striated muscle. Despite a wide range of unitary conductances (220-500 picosiemens, symmetrical cesium methanesulfonate), ryanodine locked both channels into a characteristic slow gating subconductance state, positively identifying them as RyR channels. Two populations of avian RyR channels were functionally distinguished by single channel calcium sensitivity. One population was defined by a bell-shaped calcium sensitivity analogous to the skeletal muscle RyR isoform (type I). The calcium sensitivity of the second RyR population was sigmoidal and analogous to the cardiac muscle RyR isoform (type II). These data show that there are at least two functionally distinct RyR channel populations in avian cerebellum. This leads to the possibility that these functionally distinct RyR channels are involved in different intracellular calcium signaling pathways.

Hypocalcaemia in patients with metastatic bone disease treated with denosumab.

PubMed

Body, Jean-Jacques; Bone, Henry G; de Boer, Richard H; Stopeck, Alison; Van Poznak, Catherine; Damião, Ronaldo; Fizazi, Karim; Henry, David H; Ibrahim, Toni; Lipton, Allan; Saad, Fred; Shore, Neal; Takano, Toshimi; Shaywitz, Adam J; Wang, Huei; Bracco, Oswaldo L; Braun, Ada; Kostenuik, Paul J

2015-09-01

This analysis was performed to further characterise treatment-emergent hypocalcaemia in patients with bone metastases receiving denosumab. Laboratory abnormalities and adverse events of hypocalcaemia in patients with metastatic bone disease were analysed using data from three identically designed phase 3 trials of subcutaneous denosumab 120 mg (n = 2841) versus intravenous zoledronic acid 4 mg (n = 2836). The overall incidence of laboratory events of hypocalcaemia grade ⩾ 2 was higher with denosumab (12.4%) than with zoledronic acid (5.3%). Hypocalcaemia events were primarily grade 2 in severity and usually occurred within the first 6 months of treatment. Patients who reported taking calcium and/or vitamin D supplements had a lower incidence of hypocalcaemia. Prostate cancer or small-cell lung cancer, reduced creatinine clearance and higher baseline bone turnover markers of urinary N-telopeptide of type I collagen (uNTx; > 50 versus ⩽ 50 nmol/mmol) and bone-specific alkaline phosphatase (BSAP; > 20.77 μg/L [median] versus ⩽ 20.77 μg/L) values were important risk factors for developing hypocalcaemia. The risk associated with increased baseline BSAP levels was greater among patients who had > 2 bone metastases at baseline versus those with ⩽ 2 bone metastases at baseline. Hypocalcaemia was more frequent with denosumab versus zoledronic acid, consistent with denosumab's greater antiresorptive effect. Low serum calcium levels and potential vitamin D deficiency should be corrected before initiating treatment with a potent osteoclast inhibitor, and corrected serum calcium levels should be monitored during treatment. Adequate calcium and vitamin D intake appears to substantially reduce the risk of hypocalcaemia. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

A Crash Course in Calcium Channels.

PubMed

Zamponi, Gerald W

2017-12-20

Much progress has been made in understanding the molecular physiology and pharmacology of calcium channels. Recently, there have been tremendous advances in learning about calcium channel structure and function through crystallography and cryo-electron microscopy studies. Here, I will give an overview of our knowledge about calcium channels, and highlight two recent studies that give important insights into calcium channel structure.

Defects in the calcium-binding region drastically affect the cadherin-like domains of RET tyrosine kinase.

PubMed

Gao, Chunxia; Grøtli, Morten; Eriksson, Leif A

2016-03-28

Mutations in the rearranged during transfection (RET) tyrosine kinase gene leading to gain or loss of function have been associated with the development of several human cancers and Hirschsprung's disease (HSCR). However, to what extent these mutations affect individual bio-molecular functions remains unclear. In this article, the functionally significant mutations in the RET CLD1-4 calcium-binding site which lead to HSCR, and depletion of calcium ions in the RET CLD1-4 calcium binding site, were investigated by molecular dynamics simulations--to understand the mechanistic action of the mutations or loss of calcium ions in altering the protein kinase structure, dynamics, and stability. The mutations or loss of calcium ions change the local conformation and change the free energy landscape. Specifically, the mutations and loss of calcium ions decrease the radius of gyration of the whole structure, leading to improper protein folding and GFL-GFRα contact site reduction. Furthermore, based on the most populated conformation in the wildtype MD simulations, a pharmacophore was generated by fragment docking to identify key features of the possible inhibitors targeting the calcium binding site. Overall, the findings may provide useful structural insights into the molecular mechanism underlying RET calcium-binding site mutations and assist in development of novel drugs targeting the extracellular ligand contact site of wildtype RET.

Characterization of Medicago truncatula reduced calcium oxalate crystal mutant alleles

USDA-ARS?s Scientific Manuscript database

Calcium oxalate crystal formation is common in plants. Formation of these crystals has been shown to function in plant defense, calcium regulation, and aluminum tolerance. Although calcium oxalate is common and plays important roles in plant development, our understanding of how these crystals form ...

Plant calcium oxalate crystal formation, function, and its impact on human health

USDA-ARS?s Scientific Manuscript database

Crystals of calcium oxalate have been observed among members from most taxonomic groups of photosynthetic organisms ranging from the smallest algae to the largest trees. The biological roles for calcium oxalate crystal formation in plant growth and development include high capacity calcium regulatio...

Calcium and Vitamin D Supplementation and Cognitive Impairment in the Women’s Health Initiative

PubMed Central

Rossom, Rebecca C.; Espeland, Mark A.; Manson, JoAnn E.; Dysken, Maurice W.; Johnson, Karen C.; Lane, Dorothy S.; LeBlanc, Erin S.; Lederle, Frank A.; Masaki, Kamal H.; Margolis, Karen L.

2012-01-01

Background Calcium and vitamin D are thought to play important roles in neuronal functioning. Studies have found associations between low serum vitamin D levels and reduced cognitive functioning, as well as high serum calcium levels and reduced cognitive functioning. Objectives To examine the effects of vitamin D and calcium on cognitive outcomes in elderly women. Design Post-hoc analysis of a randomized double-blinded placebo-controlled trial. Setting 40 Women’s Health Initiative clinical centers across the U.S. Participants 4143 women aged 65 years and older without probable dementia at baseline who participated in the WHI Calcium and Vitamin D trial and the Women’s Health Initiative Memory Study. Interventions 2034 women were randomized to 1000 mg of calcium carbonate combined with 400 IU of vitamin D3; 2109 women were randomized to placebo. Measurements Primary: classifications of probable dementia or mild cognitive impairment via a 4-phase protocol that included central adjudication. Secondary: global cognitive function and individual cognitive subtests. Results Mean age of participants was 71 years. During mean follow-up of 7.8 years, there were 39 cases of incident dementia among calcium plus vitamin D subjects compared to 37 cases among placebo subjects (hazard ratio=1.11, 95% CI: 0.71–1.74, p=0.64). Likewise, there were 98 cases of incident mild cognitive impairment among calcium plus vitamin D subjects compared to 108 cases among placebo subjects (hazard ratio=0.95, 95% CI: 0.72–1.25, p=0.72). There were no significant differences in incident dementia or mild cognitive impairment, or in global or domain-specific cognitive function between groups. Conclusion There was no association between treatment assignment and incident cognitive impairment. Further studies are needed to investigate the effects of vitamin D and calcium separately, on men and in other age and ethnic groups, and with other doses. PMID:23176129

Calcium release-dependent inactivation precedes formation of the tubular system in developing rat cardiac myocytes.

PubMed

Macková, Katarina; Zahradníková, Alexandra; Hoťka, Matej; Hoffmannová, Barbora; Zahradník, Ivan; Zahradníková, Alexandra

2017-12-01

Developing cardiac myocytes undergo substantial structural and functional changes transforming the mechanism of excitation-contraction coupling from the embryonic form, based on calcium influx through sarcolemmal DHPR calcium channels, to the adult form, relying on local calcium release through RYR calcium channels of sarcoplasmic reticulum stimulated by calcium influx. We characterized day-by-day the postnatal development of the structure of sarcolemma, using techniques of confocal fluorescence microscopy, and the development of the calcium current, measured by the whole-cell patch-clamp in isolated rat ventricular myocytes. We characterized the appearance and expansion of the t-tubule system and compared it with the appearance and progress of the calcium current inactivation induced by the release of calcium ions from sarcoplasmic reticulum as structural and functional measures of direct DHPR-RYR interaction. The release-dependent inactivation of calcium current preceded the development of the t-tubular system by several days, indicating formation of the first DHPR-RYR couplons at the surface sarcolemma and their later spreading close to contractile myofibrils with the growing t-tubules. Large variability of both of the measured parameters among individual myocytes indicates uneven maturation of myocytes within the growing myocardium.

Diabetic neuropathy: mechanisms, emerging treatments, and subtypes.

PubMed

Albers, James W; Pop-Busui, Rodica

2014-08-01

Diabetic neuropathies (DNs) differ in clinical course, distribution, fiber involvement (type and size), and pathophysiology, the most typical type being a length-dependent distal symmetric polyneuropathy (DSP) with differing degrees of autonomic involvement. The pathogenesis of diabetic DSP is multifactorial, including increased mitochondrial production of free radicals due to hyperglycemia-induced oxidative stress. Mechanisms that impact neuronal activity, mitochondrial function, membrane permeability, and endothelial function include formation of advanced glycosylation end products, activation of polyol aldose reductase signaling, activation of poly(ADP ribose) polymerase, and altered function of the Na(+)/K(+)-ATPase pump. Hyperglycemia-induced endoplasmic reticulum stress triggers several neuronal apoptotic processes. Additional mechanisms include impaired nerve perfusion, dyslipidemia, altered redox status, low-grade inflammation, and perturbation of calcium balance. Successful therapies require an integrated approach targeting these mechanisms. Intensive glycemic control is essential but is insufficient to prevent onset or progression of DSP, and disease-modifying treatments for DSP have been disappointing. Atypical forms of DN include subacute-onset sensory (symmetric) or motor (asymmetric) predominant conditions that are frequently painful but generally self-limited. DNs are a major cause of disability, associated with reduced quality of life and increased mortality.

Creation of a genetic calcium channel blocker by targeted gem gene transfer in the heart.

PubMed

Murata, Mitsushige; Cingolani, Eugenio; McDonald, Amy D; Donahue, J Kevin; Marbán, Eduardo

2004-08-20

Calcium channel blockers are among the most commonly used therapeutic drugs. Nevertheless, the utility of calcium channel blockers for heart disease is limited because of the potent vasodilatory effect that causes hypotension, and other side effects attributable to blockade of noncardiac channels. Therefore, focal calcium channel blockade by gene transfer is highly desirable. With a view to creating a focally applicable genetic calcium channel blocker, we overexpressed the ras-related small G-protein Gem in the heart by somatic gene transfer. Adenovirus-mediated delivery of Gem markedly decreased L-type calcium current density in ventricular myocytes, resulting in the abbreviation of action potential duration. Furthermore, transduction of Gem resulted in a significant shortening of the electrocardiographic QTc interval and reduction of left ventricular systolic function. Focal delivery of Gem to the atrioventricular (AV) node significantly slowed AV nodal conduction (prolongation of PR and AH intervals), which was effective in the reduction of heart rate during atrial fibrillation. Thus, these results indicate that gene transfer of Gem functions as a genetic calcium channel blocker, the local application of which can effectively modulate cardiac electrical and contractile function.

Calcium absorption is not increased by caseinophosphopeptides.

PubMed

Teucher, Birgit; Majsak-Newman, Gosia; Dainty, Jack R; McDonagh, David; FitzGerald, Richard J; Fairweather-Tait, Susan J

2006-07-01

One of the suggested health benefits of caseinophosphopeptides (CPPs) is their ability to enhance calcium absorption. This possibility is based on the assumption that they resist proteolysis in the upper gastrointestinal tract and maintain calcium in a soluble form at alkaline pH in the distal ileum. The effects of CPP-enriched preparations (containing candidate functional food ingredients) on calcium absorption from a calcium lactate drink were tested. A randomized crossover trial was undertaken in 15 adults in whom we measured the absorption of calcium from a calcium lactate drink (drink A: 400 mg Ca as lactate) and 2 preparations enriched with forms of CPP (1.7 g each; drinks B and C). Both drinks B and C contained 400 mg Ca as calcium lactate plus approximately 100 mg CPP-derived calcium). Each volunteer received the 3 drinks in random order. Absorption was measured by the dual-label calcium stable-isotope technique. The quantity of calcium absorbed was significantly lower from drink A (103 mg) than from drink B (117 mg; P = 0.012) or drink C (121 mg; P = 0.002), which indicated a positive effect of the CPPs. However, because the CPP preparations contributed additional calcium besides that found in the calcium lactate (drink A), fractional absorption of calcium from drink B (23%) was slightly but significantly (P = 0.015) lower than that from drink A (26%). The differences in calcium absorption are unlikely to have any biological significance. CPPs are unsuitable as candidate ingredients for functional foods that are designed to deliver improved calcium nutrition.

Role of Orai1 and store-operated calcium entry in mouse lacrimal gland signalling and function.

PubMed

Xing, Juan; Petranka, John G; Davis, Felicity M; Desai, Pooja N; Putney, James W; Bird, Gary S

2014-03-01

Lacrimal glands function to produce an aqueous layer, or tear film, that helps to nourish and protect the ocular surface. Lacrimal glands secrete proteins, electrolytes and water, and loss of gland function can result in tear film disorders such as dry eye syndrome, a widely encountered and debilitating disease in ageing populations. To combat these disorders, understanding the underlying molecular signalling processes that control lacrimal gland function will give insight into corrective therapeutic approaches. Previously, in single lacrimal cells isolated from lacrimal glands, we demonstrated that muscarinic receptor activation stimulates a phospholipase C-coupled signalling cascade involving the inositol trisphosphate-dependent mobilization of intracellular calcium and the subsequent activation of store-operated calcium entry (SOCE). Since intracellular calcium stores are finite and readily exhausted, the SOCE pathway is a critical process for sustaining and maintaining receptor-activated signalling. Recent studies have identified the Orai family proteins as critical components of the SOCE channel activity in a wide variety of cell types. In this study we characterize the role of Orai1 in the function of lacrimal glands using a mouse model in which the gene for the calcium entry channel protein, Orai1, has been deleted. Our data demonstrate that lacrimal acinar cells lacking Orai1 do not exhibit SOCE following activation of the muscarinic receptor. In comparison with wild-type and heterozygous littermates, Orai1 knockout mice showed a significant reduction in the stimulated tear production following injection of pilocarpine, a muscarinic receptor agonist. In addition, calcium-dependent, but not calcium-independent exocytotic secretion of peroxidase was eliminated in glands from knockout mice. These studies indicate a critical role for Orai1-mediated SOCE in lacrimal gland signalling and function.

Osteomalacia mimicking spondyloarthropathy: a case report.

PubMed

Garip, Y; Dedeoglu, M; Bodur, H

2014-07-01

Osteomalacia is a metabolic bone disorder characterized by impaired mineralization of bone matrix. Symptoms of osteomalacia can be confused with other conditions such as spondyloarthropathy, polymyalgia rheumatica, polymyositis, and fibromyalgia. In this case, we report a patient with axial osteomalacia who developed low back pain, morning stiffness, and "grade 3 sacroiliitis" in pelvis X-ray, leading to the misdiagnosis as seronegative spondyloarthropathy. Serum biochemical studies revealed low serum phosphorus, low 25-hydroxy vitamin D3, normal calcium, elevated parathyroid hormone, and alkaline phosphatase levels. Her symptoms were relieved with vitamin D and calcium therapy. The diagnosis of osteomalacia should be considered in case of sacroiliitis and spondylitis.

Borates

USGS Publications Warehouse

Crangle, R.D.

2013-01-01

Four minerals represent 90 percent of the borates used by industry worldwide — the sodium borates (tincal and kernite), calcium borate (colemanite) and the sodium-calcium borate (ulexite). Borax is a white crystalline substance, chemically known as sodium tetraborate decahydrate, and is found naturally as the mineral tincal. Boric acid is a colorless crystalline solid sold in technical, national formulary and special quality grades as granules or powder and marketed most often as anhydrous boric acid. Deposits of borates are associated with volcanic activity and arid climates, with the largest economically viable deposits located in the Mojave Desert of the United States near Boron, CA, the Alpide belt in southern Asia and the Andean belt of South America.

Porous polymer film calcium ion chemical sensor and method of using the same

DOEpatents

Porter, M.D.; Chau, L.K.

1991-02-12

A method of measuring calcium ions is disclosed wherein a calcium sensitive reagent, calcichrome, is immobilized on a porous polymer film. The reaction of the calcium sensitive reagent to the Ca(II) is then measured and concentration determined as a function of the reaction. 1 figure.

Porous polymer film calcium ion chemical sensor and method of using the same

DOEpatents

Porter, Marc D.; Chau, Lai-Kwan

1991-02-12

A method of measuring calcium ions is disclosed wherein a calcium sensitive reagent, calcichrome, is immobilized on a porour polymer film. The reaction of the calcium sensitive reagent to the Ca(II) is then measured and concentration determined as a function of the reaction.

Effects of Bisphosphonates and Calcium plus Vitamin-D Supplements on Cognitive Function in Postmenopausal Osteoporosis§.

PubMed

Safer, Umut; Safer, Vildan Binay; Demir, Sibel Ozbudak; Yanikoglu, Inci

2016-01-01

Postmenopausal osteoporosis has been linked to accelerated cognitive decline; however, little is known about the effects of medical treatment on cognitive functions. In this prospective study, we evaluated the effects of bisphosphonate treatment and calcium plus vitamin D supplementation on cognitive functions in 45 women with postmenopausal osteoporosis who were started on medical treatment. The medications included alendronate, zoledronic acid, risedronate, or ibandronic acid along with a low or high dose of calcium plus vitamin D supplements. The cognitive function was assessed by the mini-mental state examination (MMSE) test. All subjects underwent bone mineral density (BMD) measurement via dual-energy X-ray absorptiometry at baseline and at study completion. The mean T-score improved significantly at 1 year, except for neck of the femur area. The mean MMSE score did not change significantly at 12 months (26.40 ± 2.07 vs. 26.48 ± 2.07; p = 0.513), with no difference among bisphosphonates combined with calcium plus vitamin D. Higher dose (1200 mg/800 U/day) of calcium plus vitamin D supplementation tended to have a greater improvement as compared with lower dose (600 mg/400 U/day) (Δ MMSE: 0.11 ± 0.72 vs. -0.14 ± 0.69). Cognitive functions in the women remained unaltered, whereas bone BMD T-scores were significantly improved at the 12(th) month after the administration of bisphosphonates and calcium plus vitamin D supplements. Higher doses of calcium plus vitamin D supplements were likely to have better cognitive effects as compared with lower doses.

Calcifications in the carotid siphon inversely associate with cognitive performance in stroke-free community dwellers living in rural Ecuador (The Atahualpa Project).

PubMed

Del Brutto, Oscar H; Mera, Robertino M; Sullivan, Lauren J; Zambrano, Mauricio; King, Nathan R

2016-10-01

We aimed to assess whether carotid siphon calcifications (as seen on computed tomography) are associated with worse performance in the Montreal Cognitive Assessment in 584 stroke-free individuals living in rural Ecuador. Using mean Montreal Cognitive Assessment score of subjects with Grade 1 calcifications (23.1 ± 4.2) as the referent category, fully adjusted generalized linear models showed significant associations between severity of carotid siphon calcifications and cognitive performance (mean Montreal Cognitive Assessment scores: 20.2 ± 4.8 for Grade 2 (p = 0.004), 19.7 ± 5.3 for Grade 3 (p = 0.0001), and 18.8 ± 4.1 for Grade 4 (p = 0.02)). Predictive Montreal Cognitive Assessment score margins were higher in individuals with Grade 1 calcifications than in other groups. This study shows an inverse relationship between calcium content in the carotid siphon and cognitive performance in Amerindians.

Calcium/calmodulin-mediated signal network in plants

NASA Technical Reports Server (NTRS)

Yang, Tianbao; Poovaiah, B. W.

2003-01-01

Various extracellular stimuli elicit specific calcium signatures that can be recognized by different calcium sensors. Calmodulin, the predominant calcium receptor, is one of the best-characterized calcium sensors in eukaryotes. In recent years, completion of the Arabidopsis genome project and advances in functional genomics have helped to identify and characterize numerous calmodulin-binding proteins in plants. There are some similarities in Ca(2+)/calmodulin-mediated signaling in plants and animals. However, plants possess multiple calmodulin genes and many calmodulin target proteins, including unique protein kinases and transcription factors. Some of these proteins are likely to act as "hubs" during calcium signal transduction. Hence, a better understanding of the function of these calmodulin target proteins should help in deciphering the Ca(2+)/calmodulin-mediated signal network and its role in plant growth, development and response to environmental stimuli.

Exopolysaccharides regulate calcium flow in cariogenic biofilms

PubMed Central

Varenganayil, Muth M.; Decho, Alan W.

2017-01-01

Caries-associated biofilms induce loss of calcium from tooth surfaces in the presence of dietary carbohydrates. Exopolysaccharides (EPS) provide a matrix scaffold and an abundance of primary binding sites within biofilms. The role of EPS in binding calcium in cariogenic biofilms is only partially understood. Thus, the aim of the present study is to investigate the relationship between the calcium dissolution rates and calcium tolerance of caries-associated bacteria and yeast as well as to examine the properties of EPS to quantify its binding affinity for dissolved calcium. Calcium dissolution was measured by dissolution zones on Pikovskaya’s agar. Calcium tolerance was assessed by isothermal microcalorimetry (IMC) by adding CaCl2 to the bacterial cultures. Acid-base titration and Fourier transform infrared (FTIR) spectroscopy were used to identify possible functional groups responsible for calcium binding, which was assessed by isothermal titration calorimetry (ITC). Lactobacillus spp. and mutans streptococci demonstrated calcium dissolution in the presence of different carbohydrates. All strains that demonstrated high dissolution rates also revealed higher rates of calcium tolerance by IMC. In addition, acidic functional groups were predominantly identified as possible binding sites for calcium ions by acid-base titration and FTIR. Finally, ITC revealed EPS to have a higher binding affinity for calcium compared, for example, to lactic acid. In conclusion, this study illustrates the role of EPS in terms of the calcium tolerance of cariogenic microbiota by determining the ability of EPS to control free calcium concentrations within the biofilms as a self-regulating mode of action in the pathogenesis of dental caries. PMID:29023506

Histological comparison of autograft, allograft-DBM, xenograft, and synthetic grafts in a trabecular bone defect: an experimental study in rabbits.

PubMed

Athanasiou, Vasilis T; Papachristou, Dionysios J; Panagopoulos, Andreas; Saridis, Alkis; Scopa, Chrisoula D; Megas, Panagiotis

2010-01-01

Different types of bone-graft substitutes have been developed and are on the market worldwide to eliminate the drawbacks of autogenous grafting. This experimental animal study was undertaken to evaluate the different histological properties of various bone graft substitutes utilized in this hospital. Ninety New Zealand white rabbits were divided into six groups of 15 animals. Under general anesthesia, a 4.5 mm-wide hole was drilled into both the lateral femoral condyles of each rabbit, for a total of 180 condyles for analysis. The bone defects were filled with various grafts, these being 1) autograft, 2) DBM crunch allograft (Grafton), 3) bovine cancellous bone xenograft (Lubboc), 4) calcium phosphate hydroxyapatite substitute (Ceraform), 5) calcium sulfate substitute (Osteoset), and 6) no filling (control). The animals were sacrificed at 1, 3, and 6 months after implantation and tissue samples from the implanted areas were processed for histological evaluation. A histological grading scale was designed to determine the different histological parameters of bone healing. The highest histological grades were achieved with the use of cancellous bone autograft. Bovine xenograft (Lubboc) was the second best in the histological scale grading. The other substitutes (Grafton, Ceraform, Osteoset) had similar scores but were inferior to both allograft and xenograft. Bovine xenograft showed better biological response than the other bone graft substitutes; however, more clinical studies are necessary to determine its overall effectiveness.

Remedial Investigation Report, Presidio Main Installation, Presidio of San Francisco. Volume 1: Text

DTIC Science & Technology

1997-01-01

located in the southwestern portion of the PSF, was reportedly a low area which was filled and graded to create a flat surface for a soccer field...1991). Calcium is a macronutrient and is considered nontoxic unless present within a receptors diet at extremely high levels (Bodek et al., 1988

Enhancement of bactericidal effects of sodium hypochlorite in chiller water with food additive grade calcium hydroxide.

PubMed

Toyofuku, Chiharu; Alam, Md Shahin; Yamada, Masashi; Komura, Miyuki; Suzuki, Mayuko; Hakim, Hakimullah; Sangsriratanakul, Natthanan; Shoham, Dany; Takehara, Kazuaki

2017-06-16

An alkaline agent, namely food additive grade calcium hydroxide (FdCa(OH) 2 ) in solution at 0.17%, was evaluated for its bactericidal efficacies in chiller water with sodium hypochlorite (NaOCl) at a concentration of 200 ppm total residual chlorine. Without organic material presence, NaOCl could inactivate Salmonella Infantis and Escherichia coli within 5 sec, but in the presence of fetal bovine serum (FBS) at 0.5%, the bactericidal effects of NaOCl were diminished completely. FdCa(OH) 2 solution required 3 min to inactivate bacteria with or without 5% FBS. When NaOCl and FdCa(OH) 2 were mixed at the final concentration of 200 ppm and 0.17%, respectively, the mixed solution could inactivate bacteria at acceptable level (10 3 reduction of bacterial titer) within 30 sec in the presence of 0.5% FBS. The mixed solution also inhibited cross-contamination with S. Infantis or E. coli on chicken meats. It was confirmed and elucidated that FdCa(OH) 2 has a synergistic effect together with NaOCl for inactivating microorganisms.

Redox regulation of neuronal voltage-gated calcium channels.

PubMed

Todorovic, Slobodan M; Jevtovic-Todorovic, Vesna

2014-08-20

Voltage-gated calcium channels are ubiquitously expressed in neurons and are key regulators of cellular excitability and synaptic transmitter release. There is accumulating evidence that multiple subtypes of voltage-gated calcium channels may be regulated by oxidation and reduction. However, the redox mechanisms involved in the regulation of channel function are not well understood. Several studies have established that both T-type and high-voltage-activated subtypes of voltage-gated calcium channel can be redox-regulated. This article reviews different mechanisms that can be involved in redox regulation of calcium channel function and their implication in neuronal function, particularly in pain pathways and thalamic oscillation. A current critical issue in the field is to decipher precise mechanisms of calcium channel modulation via redox reactions. In this review we discuss covalent post-translational modification via oxidation of cysteine molecules and chelation of trace metals, and reactions involving nitric oxide-related molecules and free radicals. Improved understanding of the roles of redox-based reactions in regulation of voltage-gated calcium channels may lead to improved understanding of novel redox mechanisms in physiological and pathological processes. Identification of redox mechanisms and sites on voltage-gated calcium channel may allow development of novel and specific ion channel therapies for unmet medical needs. Thus, it may be possible to regulate the redox state of these channels in treatment of pathological process such as epilepsy and neuropathic pain.

Dependency of Calcium Alternans on Ryanodine Receptor Refractoriness

PubMed Central

Alvarez-Lacalle, Enric; Cantalapiedra, Inma R.; Peñaranda, Angelina; Cinca, Juan; Hove-Madsen, Leif; Echebarria, Blas

2013-01-01

Background Rapid pacing rates induce alternations in the cytosolic calcium concentration caused by fluctuations in calcium released from the sarcoplasmic reticulum (SR). However, the relationship between calcium alternans and refractoriness of the SR calcium release channel (RyR2) remains elusive. Methodology/Principal Findings To investigate how ryanodine receptor (RyR2) refractoriness modulates calcium handling on a beat-to-beat basis using a numerical rabbit cardiomyocyte model. We used a mathematical rabbit cardiomyocyte model to study the beat-to-beat calcium response as a function of RyR2 activation and inactivation. Bi-dimensional maps were constructed depicting the beat-to-beat response. When alternans was observed, a novel numerical clamping protocol was used to determine whether alternans was caused by oscillations in SR calcium loading or by RyR2 refractoriness. Using this protocol, we identified regions of RyR2 gating parameters where SR calcium loading or RyR2 refractoriness underlie the induction of calcium alternans, and we found that at the onset of alternans both mechanisms contribute. At low inactivation rates of the RyR2, calcium alternans was caused by alternation in SR calcium loading, while at low activation rates it was caused by alternation in the level of available RyR2s. Conclusions/Significance We have mapped cardiomyocyte beat-to-beat responses as a function of RyR2 activation and inactivation, identifying domains where SR calcium load or RyR2 refractoriness underlie the induction of calcium alternans. A corollary of this work is that RyR2 refractoriness due to slow recovery from inactivation can be the cause of calcium alternans even when alternation in SR calcium load is present. PMID:23390511

[The functions of calcium-sensing receptor in regulating mineral metabolism.

PubMed

Kinoshita, Yuka

Calcium-sensing receptor(CaSR)which belongs to a G protein-coupled receptor family is one of the key elements in regulating calcium homeostasis. CaSR has been identified as a receptor to control parathyroid hormone(PTH)secretion in parathyroid glands according to serum calcium ion(Ca2+)levels. It has also been shown that CaSR controls reabsorption of water and several cations including Ca2+and magnesium ion(Mg2+)in renal tubular cells. This review summarizes the functions and roles of CaSR in mineral metabolism that are exerted in parathyroid glands, kidney, and intestine.

Calcium intake: good for the bones but bad for the heart? An analysis of clinical studies.

PubMed

Lima, Guilherme Alcantara Cunha; Lima, Priscilla Damião Araújo; Barros, Maria da Glória Costa Reis Monteiro de; Vardiero, Lívia Paiva; Melo, Elisa Fernandes de; Paranhos-Neto, Francisco de Paula; Madeira, Miguel; Farias, Maria Lucia Fleiuss de

2016-06-01

The proper dietary calcium intake and calcium supplementation, when indicated, are important factors in the acquisition of peak bone mass during youth and in the prevention of fractures in old age. In addition to its deposition in bone, calcium confers an increase in its resistance and exhibits important activities in different enzymatic pathways in the body (e.g., neural, hormonal, muscle-related and blood clotting pathways). Thus, calcium supplementation can directly or indirectly affect important functions in the body, such as the control of blood pressure, plasma glucose, body weight, lipid profile and endothelial function. Since one publication reported increased cardiovascular risk due to calcium supplementation, many researchers have studied whether this risk actually exists; the results are conflicting, and the involved mechanisms are uncertain. However, studies that have evaluated the influence of the consumption of foods rich in calcium have reported no increase in the cardiovascular risk, which suggests that nutritional intake should be prioritized as a method for supplementation and that the use of calcium supplements should be reserved for patients who truly need supplementation and are unable to achieve the recommended daily nutritional intake of calcium.

Divergent biophysical properties, gating mechanisms, and possible functions of the two skeletal muscle Ca(V)1.1 calcium channel splice variants.

PubMed

Tuluc, Petronel; Flucher, Bernhard E

2011-12-01

Voltage-gated calcium channels are multi-subunit protein complexes that specifically allow calcium ions to enter the cell in response to membrane depolarization. But, for many years it seemed that the skeletal muscle calcium channel Ca(V)1.1 is the exception. The classical splice variant Ca(V)1.1a activates slowly, has a very small current amplitude and poor voltage sensitivity. In fact adult muscle fibers work perfectly well even in the absence of calcium influx. Recently a new splice variant of the skeletal muscle calcium channel Ca(V)1.1e has been characterized. The lack of the 19 amino acid exon 29 in this splice variant results in a rapidly activating calcium channel with high current amplitude and good voltage sensitivity. Ca(V)1.1e is the dominant channel in embryonic muscle, where the expression of this high calcium-conducting Ca(V)1.1 isoform readily explains developmental processes depending on L-type calcium currents. Moreover, the availability of these two structurally similar but functionally distinct channel variants facilitates the analysis of the molecular mechanisms underlying the unique current properties of the classical Ca(V)1.1a channel.

Calcium spikes, waves and oscillations in a large, patterned epithelial tissue

PubMed Central

Balaji, Ramya; Bielmeier, Christina; Harz, Hartmann; Bates, Jack; Stadler, Cornelia; Hildebrand, Alexander; Classen, Anne-Kathrin

2017-01-01

While calcium signaling in excitable cells, such as muscle or neurons, is extensively characterized, calcium signaling in epithelial tissues is little understood. Specifically, the range of intercellular calcium signaling patterns elicited by tightly coupled epithelial cells and their function in the regulation of epithelial characteristics are little explored. We found that in Drosophila imaginal discs, a widely studied epithelial model organ, complex spatiotemporal calcium dynamics occur. We describe patterns that include intercellular waves traversing large tissue domains in striking oscillatory patterns as well as spikes confined to local domains of neighboring cells. The spatiotemporal characteristics of intercellular waves and oscillations arise as emergent properties of calcium mobilization within a sheet of gap-junction coupled cells and are influenced by cell size and environmental history. While the in vivo function of spikes, waves and oscillations requires further characterization, our genetic experiments suggest that core calcium signaling components guide actomyosin organization. Our study thus suggests a possible role for calcium signaling in epithelia but importantly, introduces a model epithelium enabling the dissection of cellular mechanisms supporting the initiation, transmission and regeneration of long-range intercellular calcium waves and the emergence of oscillations in a highly coupled multicellular sheet. PMID:28218282

Drosophila wing imaginal discs respond to mechanical injury via slow InsP3R-mediated intercellular calcium waves

NASA Astrophysics Data System (ADS)

Restrepo, Simon; Basler, Konrad

2016-08-01

Calcium signalling is a highly versatile cellular communication system that modulates basic functions such as cell contractility, essential steps of animal development such as fertilization and higher-order processes such as memory. We probed the function of calcium signalling in Drosophila wing imaginal discs through a combination of ex vivo and in vivo imaging and genetic analysis. Here we discover that wing discs display slow, long-range intercellular calcium waves (ICWs) when mechanically stressed in vivo or cultured ex vivo. These slow imaginal disc intercellular calcium waves (SIDICs) are mediated by the inositol-3-phosphate receptor, the endoplasmic reticulum (ER) calcium pump SERCA and the key gap junction component Inx2. The knockdown of genes required for SIDIC formation and propagation negatively affects wing disc recovery after mechanical injury. Our results reveal a role for ICWs in wing disc homoeostasis and highlight the utility of the wing disc as a model for calcium signalling studies.

[The peculiarities of calcium metabolism regulation in different periods of growth and development].

PubMed

Moĭsa, S S; Nozdrachev, A D

2014-01-01

The review contains literature data about calcium metabolism regulation in different periods of growth and development. The analyses of retrospective and current sources of information about the regulation of calcium homeostasis under the theory of functional systems, the regulation of calcium metabolism in prenatal and postnatal periods of the development, the significance of calcium metabolism disturbances in the development of pathological conditions were showed.

Restricting calcium currents is required for correct fiber type specification in skeletal muscle

PubMed Central

Sultana, Nasreen; Dienes, Beatrix; Benedetti, Ariane; Tuluc, Petronel; Szentesi, Peter; Sztretye, Monika; Rainer, Johannes; Hess, Michael W.; Schwarzer, Christoph; Obermair, Gerald J.; Csernoch, Laszlo

2016-01-01

ABSTRACT Skeletal muscle excitation-contraction (EC) coupling is independent of calcium influx. In fact, alternative splicing of the voltage-gated calcium channel CaV1.1 actively suppresses calcium currents in mature muscle. Whether this is necessary for normal development and function of muscle is not known. However, splicing defects that cause aberrant expression of the calcium-conducting developmental CaV1.1e splice variant correlate with muscle weakness in myotonic dystrophy. Here, we deleted CaV1.1 (Cacna1s) exon 29 in mice. These mice displayed normal overall motor performance, although grip force and voluntary running were reduced. Continued expression of the developmental CaV1.1e splice variant in adult mice caused increased calcium influx during EC coupling, altered calcium homeostasis, and spontaneous calcium sparklets in isolated muscle fibers. Contractile force was reduced and endurance enhanced. Key regulators of fiber type specification were dysregulated and the fiber type composition was shifted toward slower fibers. However, oxidative enzyme activity and mitochondrial content declined. These findings indicate that limiting calcium influx during skeletal muscle EC coupling is important for the secondary function of the calcium signal in the activity-dependent regulation of fiber type composition and to prevent muscle disease. PMID:26965373

Depletion of calcium stores regulates calcium influx and signal transmission in rod photoreceptors

PubMed Central

Szikra, Tamas; Cusato, Karen; Thoreson, Wallace B; Barabas, Peter; Bartoletti, Theodore M; Krizaj, David

2008-01-01

Tonic synapses are specialized for sustained calcium entry and transmitter release, allowing them to operate in a graded fashion over a wide dynamic range. We identified a novel plasma membrane calcium entry mechanism that extends the range of rod photoreceptor signalling into light-adapted conditions. The mechanism, which shares molecular and physiological characteristics with store-operated calcium entry (SOCE), is required to maintain baseline [Ca2+]i in rod inner segments and synaptic terminals. Sustained Ca2+ entry into rod cytosol is augmented by store depletion, blocked by La3+ and Gd3+ and suppressed by organic antagonists MRS-1845 and SKF-96365. Store depletion and the subsequent Ca2+ influx directly stimulated exocytosis in terminals of light-adapted rods loaded with the activity-dependent dye FM1–43. Moreover, SOCE blockers suppressed rod-mediated synaptic inputs to horizontal cells without affecting presynaptic voltage-operated Ca2+ entry. Silencing of TRPC1 expression with small interference RNA disrupted SOCE in rods, but had no effect on cone Ca2+ signalling. Rods were immunopositive for TRPC1 whereas cone inner segments immunostained with TRPC6 channel antibodies. Thus, SOCE modulates Ca2+ homeostasis and light-evoked neurotransmission at the rod photoreceptor synapse mediated by TRPC1. PMID:18755743

Association of calcium sensing receptor polymorphisms at rs1801725 with circulating calcium in breast cancer patients.

PubMed

Wang, Li; Widatalla, Sarrah E; Whalen, Diva S; Ochieng, Josiah; Sakwe, Amos M

2017-08-02

Breast cancer (BC) patients with late-stage and/or rapidly growing tumors are prone to develop high serum calcium levels which have been shown to be associated with larger and aggressive breast tumors in post and premenopausal women respectively. Given the pivotal role of the calcium sensing receptor (CaSR) in calcium homeostasis, we evaluated whether polymorphisms of the CASR gene at rs1801725 and rs1801726 SNPs in exon 7, are associated with circulating calcium levels in African American and Caucasian control subjects and BC cases. In this retrospective case-control study, we assessed the mean circulating calcium levels, the distribution of two inactivating CaSR SNPs at rs1801725 and rs1801726 in 199 cases and 384 age-matched controls, and used multivariable regression analysis to determine whether these SNPs are associated with circulating calcium in control subjects and BC cases. We found that the mean circulating calcium levels in African American subjects were higher than those in Caucasian subjects (p < 0.001). As expected, the mean calcium levels were higher in BC cases compared to control subjects (p < 0.001), but the calcium levels in BC patients were independent of race. We also show that in BC cases and control subjects, the major alleles at rs1801725 (G/T, A986S) and at rs1801726 (C/G, Q1011E) were common among Caucasians and African Americans respectively. Compared to the wild type alleles, polymorphisms at the rs1801725 SNP were associated with higher calcium levels (p = 0.006) while those at rs1801726 were not. Using multivariable linear mixed-effects models and adjusting for age and race, we show that circulating calcium levels in BC cases were associated with tumor grade (p = 0.009), clinical stage (p = 0.003) and more importantly, with inactivating mutations of the CASR at the rs1801725 SNP (p = 0.038). These data suggest that decreased sensitivity of the CaSR to calcium due to inactivating polymorphisms at rs1801725, may predispose up to 20% of BC cases to high circulating calcium-associated larger and/or aggressive breast tumors.

Study on the Equilibrium Between Liquid Iron and Calcium Vapor

NASA Astrophysics Data System (ADS)

Berg, Martin; Lee, Jaewoo; Sichen, Du

2017-06-01

The solubility of calcium in liquid iron at 1823 K and 1873 K (1550 °C and 1600 °C) as a function of calcium potential was studied experimentally. The measurements were performed using a closed molybdenum holder in which liquid calcium and liquid iron were held at different temperatures. The results indicate a linear relationship between the activity of calcium, relative to pure liquid calcium, and the mole fraction of dissolved calcium in liquid iron, with a negligible temperature dependency in the ranges studied. The activity coefficient of calcium in liquid iron at infinite dilution, γ_{Ca(l0°, was calculated as 1551.

Correlation between carotid bifurcation calcium burden on non-enhanced CT and percentage stenosis, as confirmed by digital subtraction angiography

PubMed Central

Sarikaya, B; Lohman, B; Mckinney, A M; Gadani, S; Irfan, M; Lucato, L

2012-01-01

Objectives Previous evidence supports a direct relationship between the calcium burden (volume) on post-contrast CT with the percent internal carotid artery (ICA) stenosis at the carotid bifurcation. We sought to further investigate this relationship by comparing non-enhanced CT (NECT) and digital subtraction angiography (DSA). Methods 50 patients (aged 41–82 years) were retrospectively identified who had undergone cervical NECT and DSA. A 64-multidetector array CT (MDCT) scanner was utilised and the images reviewed using preset window widths/levels (30/300) optimised to calcium, with the volumes measured via three-dimensional reconstructive software. Stenosis measurements were performed on DSA and luminal diameter stenoses >40% were considered “significant”. Volume thresholds of 0.01, 0.03, 0.06, 0.09 and 0.12 cm3 were utilised and Pearson'S correlation coefficient (r) was calculated to correlate the calcium volume with percent stenosis. Results Of 100 carotid bifurcations, 88 were available and of these 7 were significantly stenotic. The NECT calcium volume moderately correlated with percent stenosis on DSA r=0.53 (p<0.01). A moderate–strong correlation was found between the square root of calcium volume on NECT with percent stenosis on DSA (r=0.60, p<0.01). Via a receiver operating characteristic curve, 0.06 cm3 was determined to be the best threshold (sensitivity 100%, specificity 90.1%, negative predictive value 100% and positive predictive value 46.7%) for detecting significant stenoses. Conclusion This preliminary investigation confirms a correlation between carotid bifurcation calcium volume and percent ICA stenosis and is promising for the optimal threshold for stenosis detection. Future studies could utilise calcium volumes to create a “score” that could predict high grade stenosis. PMID:21896662

Phosphorylation and calcium antagonistically tune myosin-binding protein C’s structure and function

PubMed Central

Previs, Michael J.; Mun, Ji Young; Michalek, Arthur J.; Previs, Samantha Beck; Gulick, James; Robbins, Jeffrey; Warshaw, David M.; Craig, Roger

2016-01-01

During each heartbeat, cardiac contractility results from calcium-activated sliding of actin thin filaments toward the centers of myosin thick filaments to shorten cellular length. Cardiac myosin-binding protein C (cMyBP-C) is a component of the thick filament that appears to tune these mechanochemical interactions by its N-terminal domains transiently interacting with actin and/or the myosin S2 domain, sensitizing thin filaments to calcium and governing maximal sliding velocity. Both functional mechanisms are potentially further tunable by phosphorylation of an intrinsically disordered, extensible region of cMyBP-C’s N terminus, the M-domain. Using atomic force spectroscopy, electron microscopy, and mutant protein expression, we demonstrate that phosphorylation reduced the M-domain’s extensibility and shifted the conformation of the N-terminal domain from an extended structure to a compact configuration. In combination with motility assay data, these structural effects of M-domain phosphorylation suggest a mechanism for diminishing the functional potency of individual cMyBP-C molecules. Interestingly, we found that calcium levels necessary to maximally activate the thin filament mitigated the structural effects of phosphorylation by increasing M-domain extensibility and shifting the phosphorylated N-terminal fragments back to the extended state, as if unphosphorylated. Functionally, the addition of calcium to the motility assays ablated the impact of phosphorylation on maximal sliding velocities, fully restoring cMyBP-C’s inhibitory capacity. We conclude that M-domain phosphorylation may have its greatest effect on tuning cMyBP-C’s calcium-sensitization of thin filaments at the low calcium levels between contractions. Importantly, calcium levels at the peak of contraction would allow cMyBP-C to remain a potent contractile modulator, regardless of cMyBP-C’s phosphorylation state. PMID:26908872

Optimization of Direct Fibroblast Reprogramming to Cardiomyocytes Using Calcium Activity as a Functional Measure of Success

PubMed Central

Addis, Russell C.; Ifkovits, Jamie L.; Pinto, Filipa; Kellam, Lori D.; Esteso, Paul; Rentschler, Stacey; Christoforou, Nicolas; Epstein, Jonathan A.; Gearhart, John D.

2013-01-01

Direct conversion of fibroblasts to induced cardiomyocytes (iCMs) has great potential for regenerative medicine. Recent publications have reported significant progress, but the evaluation of reprogramming has relied upon non-functional measures such as flow cytometry for cardiomyocyte markers or GFP expression driven by a cardiomyocyte-specific promoter. The issue is one of practicality: the most stringent measures - electrophysiology to detect cell excitation and the presence of spontaneously contracting myocytes - are not readily quantifiable in the large numbers of cells screened in reprogramming experiments. However, excitation and contraction are linked by a third functional characteristic of cardiomyocytes: the rhythmic oscillation of intracellular calcium levels. We set out to optimize direct conversion of fibroblasts to iCMs with a quantifiable calcium reporter to rapidly assess functional transdifferentiation. We constructed a reporter system in which the calcium indicator GCaMP is driven by the cardiomyocyte-specific Troponin T promoter. Using calcium activity as our primary outcome measure, we compared several published combinations of transcription factors along with novel combinations in mouse embryonic fibroblasts. The most effective combination consisted of Hand2, Nkx2.5, Gata4, Mef2c, and Tbx5 (HNGMT). This combination is >50-fold more efficient than GMT alone and produces iCMs with cardiomyocyte marker expression, robust calcium oscillation, and spontaneous beating that persists for weeks following inactivation of reprogramming factors. HNGMT is also significantly more effective than previously published factor combinations for the transdifferentiation of adult mouse cardiac fibroblasts to iCMs. Quantification of calcium function is a convenient and effective means for the identification and evaluation of cardiomyocytes generated by direct reprogramming. Using this stringent outcome measure, we conclude that HNGMT produces iCMs more efficiently than previously published methods. PMID:23591016

Mineral and nitrogen metabolic studies, experiment M071

NASA Technical Reports Server (NTRS)

Whedon, G. D.; Lutwak, L.; Rambaut, P. C.; Whittle, M. W.; Smith, M. C., Jr.; Reid, J.; Leach, C. S.; Stadler, C. R.; Sanford, D. D.

1977-01-01

The similarity between bed rest test and space flight effects on human mineral and nitrogen metabolisms indicates impairment of capable musculoskeletal functions. A pattern of urinary calcium increases and total calcium shifts suggests that calcium losses continue with time. Significant losses of nitrogen and phosphorus are associated with reduction in muscle tissue. It is concluded that capable musculoskeletal function is likely to be impaired during space flights of 1 1/2 to 3 years duration.

Effect of incorporation of calcium lactate on physico-chemical, textural, and sensory properties of restructured buffalo meat loaves

PubMed Central

Irshad, A.; Sharma, B. D.; Ahmed, S. R.; Talukder, S.; Malav, O. P.; Kumar, Ashish

2016-01-01

Aim: The present study was conducted to develop a functional meat product by fortifying calcium (in the form of calcium lactate) with restructured buffalo meat loaf (RBML). Materials and Methods: Deboned buffalo meat obtained from the carcass of adult female buffalo within 5-6 h of slaughter and stored under frozen condition. Calcium fortified RBML were prepared by replacing the lean buffalo meat with calcium lactate powder at 0%, 1%, 1.25%, and 1.5% level through the pre-standardized procedure. The developed products were evaluated for physico-chemical properties, proximate composition, calcium concentration (mg/100 g), water activity (aw), Lovibond® tintometer color units, texture profile analysis (TPA), and sensory qualities as per-standard procedures. Results: Of the various product quality parameters evaluated, cooking yield (%), product pH, moisture (%), protein (%), fat (%), and water activity (aw) decreases significantly with increasing level of calcium lactate. Calcium content of fortified functional RBMLs was 135.02, 165.73, and 203.85 mg/100 g as compared to 6.48 mg/100 g in control. Most of the sensory scores at 1% and 1.25% levels of calcium lactate in treatment products remained comparable among themselves and control product, with a gradual decline. Conclusions: The present study concluded that 1.25% calcium lactate was the optimum level for the fortification of calcium in RBML without affecting the textural and sensory properties which could meet out 15% of recommended dietary allowance for calcium. PMID:27051201

Effect of incorporation of calcium lactate on physico-chemical, textural, and sensory properties of restructured buffalo meat loaves.

PubMed

Irshad, A; Sharma, B D; Ahmed, S R; Talukder, S; Malav, O P; Kumar, Ashish

2016-02-01

The present study was conducted to develop a functional meat product by fortifying calcium (in the form of calcium lactate) with restructured buffalo meat loaf (RBML). Deboned buffalo meat obtained from the carcass of adult female buffalo within 5-6 h of slaughter and stored under frozen condition. Calcium fortified RBML were prepared by replacing the lean buffalo meat with calcium lactate powder at 0%, 1%, 1.25%, and 1.5% level through the pre-standardized procedure. The developed products were evaluated for physico-chemical properties, proximate composition, calcium concentration (mg/100 g), water activity (aw), Lovibond(®) tintometer color units, texture profile analysis (TPA), and sensory qualities as per-standard procedures. Of the various product quality parameters evaluated, cooking yield (%), product pH, moisture (%), protein (%), fat (%), and water activity (aw) decreases significantly with increasing level of calcium lactate. Calcium content of fortified functional RBMLs was 135.02, 165.73, and 203.85 mg/100 g as compared to 6.48 mg/100 g in control. Most of the sensory scores at 1% and 1.25% levels of calcium lactate in treatment products remained comparable among themselves and control product, with a gradual decline. The present study concluded that 1.25% calcium lactate was the optimum level for the fortification of calcium in RBML without affecting the textural and sensory properties which could meet out 15% of recommended dietary allowance for calcium.

D1 receptors physically interact with N-type calcium channels to regulate channel distribution and dendritic calcium entry.

PubMed

Kisilevsky, Alexandra E; Mulligan, Sean J; Altier, Christophe; Iftinca, Mircea C; Varela, Diego; Tai, Chao; Chen, Lina; Hameed, Shahid; Hamid, Jawed; Macvicar, Brian A; Zamponi, Gerald W

2008-05-22

Dopamine signaling through D1 receptors in the prefrontal cortex (PFC) plays a critical role in the maintenance of higher cognitive functions, such as working memory. At the cellular level, these functions are predicated to involve alterations in neuronal calcium levels. The dendrites of PFC neurons express D1 receptors and N-type calcium channels, yet little information exists regarding their coupling. Here, we show that D1 receptors potently inhibit N-type channels in dendrites of rat PFC neurons. Using coimmunoprecipitation, we demonstrate the existence of a D1 receptor-N-type channel signaling complex in this region, and we provide evidence for a direct receptor-channel interaction. Finally, we demonstrate the importance of this complex to receptor-channel colocalization in heterologous systems and in PFC neurons. Our data indicate that the N-type calcium channel is an important physiological target of D1 receptors and reveal a mechanism for D1 receptor-mediated regulation of cognitive function in the PFC.

STIM1 signaling controls store operated calcium entry required for development and contractile function in skeletal muscle

PubMed Central

Stiber, Jonathan; Hawkins, April; Zhang, Zhu-Shan; Wang, Sunny; Burch, Jarrett; Graham, Victoria; Ward, Cary C.; Seth, Malini; Finch, Elizabeth; Malouf, Nadia; Williams, R. Sanders; Eu, Jerry P.; Rosenberg, Paul

2009-01-01

It is now well established that stromal interaction molecule 1 (STIM1) is the calcium sensor of endoplasmic reticulum (ER) stores required to activate store-operated calcium entry (SOC) channels at the surface of non-excitable cells. Yet little is known about STIM1 in excitable cells such as striated muscle where the complement of calcium regulatory molecules is rather disparate from that of non-excitable cells. Here, we show that STIM1 is expressed in both myotubes and adult skeletal muscle. Myotubes lacking functional STIM1 fail to exhibit SOC and fatigue rapidly. Moreover, mice lacking functional STIM1 die perinatally from a skeletal myopathy. In addition, STIM1 haploinsufficiency confers a contractile defect only under conditions where rapid refilling of stores would be needed. These findings provide novel insight to the role of STIM1 in skeletal muscle and suggest that STIM1 has a universal role as an ER/SR calcium sensor in both excitable and non-excitable cells. PMID:18488020

Optimized ratiometric calcium sensors for functional in vivo imaging of neurons and T lymphocytes.

PubMed

Thestrup, Thomas; Litzlbauer, Julia; Bartholomäus, Ingo; Mues, Marsilius; Russo, Luigi; Dana, Hod; Kovalchuk, Yuri; Liang, Yajie; Kalamakis, Georgios; Laukat, Yvonne; Becker, Stefan; Witte, Gregor; Geiger, Anselm; Allen, Taylor; Rome, Lawrence C; Chen, Tsai-Wen; Kim, Douglas S; Garaschuk, Olga; Griesinger, Christian; Griesbeck, Oliver

2014-02-01

The quality of genetically encoded calcium indicators (GECIs) has improved dramatically in recent years, but high-performing ratiometric indicators are still rare. Here we describe a series of fluorescence resonance energy transfer (FRET)-based calcium biosensors with a reduced number of calcium binding sites per sensor. These 'Twitch' sensors are based on the C-terminal domain of Opsanus troponin C. Their FRET responses were optimized by a large-scale functional screen in bacterial colonies, refined by a secondary screen in rat hippocampal neuron cultures. We tested the in vivo performance of the most sensitive variants in the brain and lymph nodes of mice. The sensitivity of the Twitch sensors matched that of synthetic calcium dyes and allowed visualization of tonic action potential firing in neurons and high resolution functional tracking of T lymphocytes. Given their ratiometric readout, their brightness, large dynamic range and linear response properties, Twitch sensors represent versatile tools for neuroscience and immunology.

Near-membrane electric field calcium ion dehydration.

PubMed

Barger, James P; Dillon, Patrick F

2016-12-01

The dehydration of ion-water complexes prior to ion channel transit has focused on channel protein-mediated dissociation of water. Ion dehydration by the membrane electric field has not previously been considered. Near membrane electric fields have previously been shown to cause the disassociation of non-covalently bound small molecule-small molecule, small molecule-protein, and protein-protein complexes. It is well known that cosmotropic, structure making ions such as calcium and sodium significantly bind multiple water ions in solution. It is also known that these ions are often not hydrated as they pass through membrane ion channels. Using capillary electrophoresis, the range of electric fields needed to strip water molecules from calcium ions has been measured. Ion migration velocity is a linear function of the electric field. At low electric fields, the migration rate of calcium ion was shown to be linearly related to the applied electric field. Using a form of the Stoke's equation applicable to ion migration, the hydrated calcium radius was found to be 0.334nm, corresponding to a water hydration shell of 5.09 water molecules. At higher electric fields, the slope of the calcium migration velocity as a function of the electric field increased, which was modeled as a decrease in the radius of the migrating ion as the water was removed. Using a tanh function to model the transition of the ion from a hydrated to a stripped state, the transition had a midpoint at 446V/cm, and was 88% complete at 587V/cm with a correlation coefficient of 0.9996. The migration velocity of the stripped calcium ion was found to be a function of both the decrease in radius and an increase in the effective, electronic viscosity of the dipole medium through which the dehydrated ion moved. The size of the electric field needed to dehydrate calcium occurs 6-7nm from the cell membrane. Calcium ions within this distance from the membrane will be devoid of water molecules when they reach the calcium selective channel pore entrances, all known to be approximately 1-2nm from the membrane. No matter what the calcium pore structure, calcium ions reaching the channel entrance will be devoid of a water shell. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Novel Ex Vivo Method for Visualizing Live-Cell Calcium Response Behavior in Intact Human Tumors.

PubMed

Koh, James; Hogue, Joyce A; Sosa, Julie A

2016-01-01

The functional impact of intratumoral heterogeneity has been difficult to assess in the absence of a means to interrogate dynamic, live-cell biochemical events in the native tissue context of a human tumor. Conventional histological methods can reveal morphology and static biomarker expression patterns but do not provide a means to probe and evaluate tumor functional behavior and live-cell responsiveness to experimentally controlled stimuli. Here, we describe an approach that couples vibratome-mediated viable tissue sectioning with live-cell confocal microscopy imaging to visualize human parathyroid adenoma tumor cell responsiveness to extracellular calcium challenge. Tumor sections prepared as 300 micron-thick tissue slices retain viability throughout a >24 hour observation period and retain the native architecture of the parental tumor. Live-cell observation of biochemical signaling in response to extracellular calcium challenge in the intact tissue slices reveals discrete, heterogeneous kinetic waveform categories of calcium agonist reactivity within each tumor. Plotting the proportion of maximally responsive tumor cells as a function of calcium concentration yields a sigmoid dose-response curve with a calculated calcium EC50 value significantly elevated above published reference values for wild-type calcium-sensing receptor (CASR) sensitivity. Subsequent fixation and immunofluorescence analysis of the functionally evaluated tissue specimens allows alignment and mapping of the physical characteristics of individual cells within the tumor to specific calcium response behaviors. Evaluation of the relative abundance of intracellular PTH in tissue slices challenged with variable calcium concentrations demonstrates that production of the hormone can be dynamically manipulated ex vivo. The capability of visualizing live human tumor tissue behavior in response to experimentally controlled conditions opens a wide range of possibilities for personalized ex vivo therapeutic testing. This highly adaptable system provides a unique platform for live-cell ex vivo provocative testing of human tumor responsiveness to a range of physiological agonists or candidate therapeutic compounds.

Redox Regulation of Neuronal Voltage-Gated Calcium Channels

PubMed Central

Jevtovic-Todorovic, Vesna

2014-01-01

Abstract Significance: Voltage-gated calcium channels are ubiquitously expressed in neurons and are key regulators of cellular excitability and synaptic transmitter release. There is accumulating evidence that multiple subtypes of voltage-gated calcium channels may be regulated by oxidation and reduction. However, the redox mechanisms involved in the regulation of channel function are not well understood. Recent Advances: Several studies have established that both T-type and high-voltage-activated subtypes of voltage-gated calcium channel can be redox-regulated. This article reviews different mechanisms that can be involved in redox regulation of calcium channel function and their implication in neuronal function, particularly in pain pathways and thalamic oscillation. Critical Issues: A current critical issue in the field is to decipher precise mechanisms of calcium channel modulation via redox reactions. In this review we discuss covalent post-translational modification via oxidation of cysteine molecules and chelation of trace metals, and reactions involving nitric oxide-related molecules and free radicals. Improved understanding of the roles of redox-based reactions in regulation of voltage-gated calcium channels may lead to improved understanding of novel redox mechanisms in physiological and pathological processes. Future Directions: Identification of redox mechanisms and sites on voltage-gated calcium channel may allow development of novel and specific ion channel therapies for unmet medical needs. Thus, it may be possible to regulate the redox state of these channels in treatment of pathological process such as epilepsy and neuropathic pain. Antioxid. Redox Signal. 21, 880–891. PMID:24161125

Incidence of hypocalcemia in patients receiving denosumab for prevention of skeletal-related events in bone metastasis.

PubMed

Yerram, Prakirthi; Kansagra, Shraddha; Abdelghany, Osama

2017-04-01

Background Denosumab therapy is commonly used for the prevention of skeletal-related events in patients with bone metastasis. However, a common side effect of denosumab is hypocalcemia. Objective The aim of the study is to determine the incidence of hypocalcemia in patients receiving denosumab for prevention of skeletal-related events in bone metastasis and evaluate risk factors for developing hypocalcemia. Methods This was a retrospective medication use evaluation reviewing the incidence of hypocalcemia in patients receiving outpatient denosumab for prevention of skeletal-related events at Yale-New Haven Hospital. Additionally, various risk factors were reviewed to determine their risk of developing hypocalcemia. Results As per Common Terminology Criteria for Adverse Events v4.03, of the 106 patients included in the study population, 37 (35%) patients had an incidence of hypocalcemia within 30 days of denosumab administration. Fourteen patients (13.2%) had an incidence of grade 1, 13 patients (12.3%) had an incidence of grade 2 hypocalcemia, and 7 patients (6.6%) had an incidence of grade 3 hypocalcemia. Grade 4 hypocalcemia occurred in three (2.8%) patients. Calcium supplementation did not decrease the risk of developing hypocalcemia. Patients who had one or more episodes of acute kidney insufficiency were at a higher risk of developing hypocalcemia (odds ratio = 7.5 (95% confidence interval = 1.8-36.3), p = 0.001). Conclusion This study found that the overall incidence of hypocalcemia and severe hypocalcemia was higher than reported in clinical trials. Additionally, calcium supplementation did not have an effect on incidence of hypocalcemia, while patients who experienced acute kidney insufficiency while on denosumab had a higher likelihood of developing hypocalcemia.

Evaluation of different grades of ginseng using Fourier-transform infrared and two-dimensional infrared correlation spectroscopy

NASA Astrophysics Data System (ADS)

Zhang, Yan-ling; Chen, Jian-bo; Lei, Yu; Zhou, Qun; Sun, Su-qin; Noda, Isao

2010-06-01

Ginseng is one of the most widely used herbal medicines which have many kinds of pharmaceutical values. The discrimination of grades of ginseng includes the cultivation types and the growth years herein. To evaluate the different grades of ginseng, the fibrous roots and rhizome roots of ginseng were analyzed by Fourier-transform infrared and two-dimensional infrared correlation spectroscopy in this paper. The fibrous root and rhizome root of ginseng have different content of starch, calcium oxalate and other components. For the fibrous roots of ginseng, mountain cultivation ginseng (MCG), garden cultivation ginseng (GCG) and transplanted cultivation ginseng (TCG) have clear difference in the infrared spectra and second derivative spectra in the range of 1800-400 cm -1, and clearer difference was observed in the range of 1045-1160 and 1410-1730 cm -1 in 2D synchronous correlation spectra. Three kinds of ginseng can be clustered very well by using SIMCA analysis on the basis of PCA as well. For the rhizome roots, the content of calcium oxalate and starch change with growth years in the IR spectra, and some useful procedure can be obtained by the analysis of 2D IR synchronous spectra in the range of 1050-1415 cm -1. Also, ginsengs cultivated in different growth years were clustered perfectly by using SIMCA analysis. The results suggested that different grades of ginseng can be well recognized using the mid-infrared spectroscopy assisted by 2D IR correlation spectroscopy, which provide the macro-fingerprint characteristics of ginseng in different parts and supplied a rapid, effective approach for the evaluation of the quality of ginseng.

Molecular Dynamics Simulations of Membrane-Bound STIM1 to Investigate Conformational Changes during STIM1 Activation upon Calcium Release.

PubMed

Mukherjee, Sreya; Karolak, Aleksandra; Debant, Marjolaine; Buscaglia, Paul; Renaudineau, Yves; Mignen, Olivier; Guida, Wayne C; Brooks, Wesley H

2017-02-27

Calcium is involved in important intracellular processes, such as intracellular signaling from cell membrane receptors to the nucleus. Typically, calcium levels are kept at less than 100 nM in the nucleus and cytosol, but some calcium is stored in the endoplasmic reticulum (ER) lumen for rapid release to activate intracellular calcium-dependent functions. Stromal interacting molecule 1 (STIM1) plays a critical role in early sensing of changes in the ER's calcium level, especially when there is a sudden release of stored calcium from the ER. Inactive STIM1, which has a bound calcium ion, is activated upon ion release. Following activation of STIM1, there is STIM1-assisted initiation of extracellular calcium entry through channels in the cell membrane. This extracellular calcium entering the cell then amplifies intracellular calcium-dependent actions. At the end of the process, ER levels of stored calcium are reestablished. The main focus of this work was to study the conformational changes accompanying homo- or heterodimerization of STIM1. For this purpose, the ER luminal portion of STIM1 (residues 58-236), which includes the sterile alpha motif (SAM) domain plus the calcium-binding EF-hand domains 1 and 2 attached to the STIM1 transmembrane region (TM), was modeled and embedded in a virtual membrane. Next, molecular dynamics simulations were performed to study the conformational changes that take place during STIM1 activation and subsequent protein-protein interactions. Indeed, the simulations revealed exposure of residues in the EF-hand domains, which may be important for dimerization steps. Altogether, understanding conformational changes in STIM1 can help in drug discovery when targeting this key protein in intracellular calcium functions.

Use of a purified and functional recombinant calcium-channel beta4 subunit in surface-plasmon resonance studies.

PubMed Central

Geib, Sandrine; Sandoz, Guillaume; Mabrouk, Kamel; Matavel, Alessandra; Marchot, Pascale; Hoshi, Toshinori; Villaz, Michel; Ronjat, Michel; Miquelis, Raymond; Lévêque, Christian; de Waard, Michel

2002-01-01

Native high-voltage-gated calcium channels are multi-subunit complexes comprising a pore-forming subunit Ca(v) and at least two auxiliary subunits alpha(2)delta and beta. The beta subunit facilitates cell-surface expression of the channel and contributes significantly to its biophysical properties. In spite of its importance, detailed structural and functional studies are hampered by the limited availability of native beta subunit. Here, we report the purification of a recombinant calcium-channel beta(4) subunit from bacterial extracts by using a polyhistidine tag. The purified protein is fully functional since it binds on the alpha1 interaction domain, its main Ca(v)-binding site, and regulates the activity of P/Q calcium channel expressed in Xenopus oocytes in a similar way to the beta(4) subunit produced by cRNA injection. We took advantage of the functionality of the purified material to (i) develop an efficient surface-plasmon resonance assay of the interaction between two calcium channel subunits and (ii) measure, for the first time, the affinity of the recombinant His-beta(4) subunit for the full-length Ca(v)2.1 channel. The availability of this purified material and the development of a surface-plasmon resonance assay opens two immediate research perspectives: (i) drug screening programmes applied to the Ca(v)/beta interaction and (ii) crystallographic studies of the calcium-channel beta(4) subunit. PMID:11988102

New evidence about the relationship between water channel activity and calcium in salinity-stressed pepper plants.

PubMed

Cabañero, Francisco J; Martínez-Ballesta, M Carmen; Teruel, José A; Carvajal, Micaela

2006-02-01

This study, of how Ca2+ availability (intracellular, extracellular or linked to the membrane) influences the functionality of aquaporins of pepper (Capsicum annuum L.) plants grown under salinity stress, was carried out in plants treated with NaCl (50 mM), CaCl2 (10 mM), and CaCl2 (10 mM) + NaCl (50 mM). For this, water transport through the plasma membrane of isolated protoplasts, and the involvement of aquaporins and calcium (extracellular, intracellular and linked to the membrane) has been determined. After these treatments, it could be seen that the calcium concentration was reduced in the apoplast, in the cells and on the plasma membrane of roots of pepper plants grown under saline conditions; these concentrations were increased or restored when extra calcium was added to the nutrient solution. Protoplasts extracted from plants grown under Ca2+ starvation showed no aquaporin functionality. However, for the protoplasts to which calcium was added, an increase of aquaporin functionality of the plasma membrane was observed [osmotic water permeability (Pf) inhibition after Hg addition]. Interestingly, when verapamil (a Ca2+ channel blocker) was added, no functionality was observed, even when Ca2+ was added with verapamil. Therefore, calcium seems to be involved in plasma membrane aquaporin regulation via a chain of processes within the cell but not by alteration of the stability of the plasma membrane.

Targeting Cellular Calcium Homeostasis to Prevent Cytokine-Mediated Beta Cell Death.

PubMed

Clark, Amy L; Kanekura, Kohsuke; Lavagnino, Zeno; Spears, Larry D; Abreu, Damien; Mahadevan, Jana; Yagi, Takuya; Semenkovich, Clay F; Piston, David W; Urano, Fumihiko

2017-07-17

Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets. These agents are also able to restore cytokine-mediated suppression of functional ER calcium release. In addition, sitagliptin preserves function of the ER calcium pump, sarco-endoplasmic reticulum Ca 2+ -ATPase (SERCA), and decreases levels of the pro-apoptotic protein thioredoxin-interacting protein (TXNIP). Supporting the role of TXNIP in cytokine-mediated cell death, knock down of TXNIP in INS1-E cells prevents cytokine-mediated beta cell death. Our findings demonstrate that modulation of dynamic cellular calcium homeostasis and TXNIP suppression present viable pharmacologic targets to prevent cytokine-mediated beta cell loss in diabetes.

Intra-amniotic administration (Gallus gallus) of cicer arietinum and lens culinaris prebiotics extracts and duck egg white peptides affects calcium status and intestinal functionality

USDA-ARS?s Scientific Manuscript database

Calcium (Ca) is one of the most abundant inorganic elements in the human body and has many important physiological roles. Prebiotics and bioactive peptides are two important substances used to promote calcium uptake. However, the difference in mechanisms of the calcium uptake from these two suppleme...

Atorvastatin affects negatively respiratory function of isolated endothelial mitochondria.

PubMed

Broniarek, Izabela; Jarmuszkiewicz, Wieslawa

2018-01-01

The purpose of this research was to elucidate the direct effects of two popular blood cholesterol-lowering drugs used to treat cardiovascular diseases, atorvastatin and pravastatin, on respiratory function, membrane potential, and reactive oxygen species formation in mitochondria isolated from human umbilical vein endothelial cells (EA.hy926 cell line). Hydrophilic pravastatin did not significantly affect endothelial mitochondria function. In contrast, hydrophobic calcium-containing atorvastatin induced a loss of outer mitochondrial membrane integrity, an increase in hydrogen peroxide formation, and reductions in maximal (phosphorylating or uncoupled) respiratory rate, membrane potential and oxidative phosphorylation efficiency. The atorvastatin-induced changes indicate an impairment of mitochondrial function at the level of ATP synthesis and at the level of the respiratory chain, likely at complex I and complex III. The atorvastatin action on endothelial mitochondria was highly dependent on calcium ions and led to a disturbance in mitochondrial calcium homeostasis. Uptake of calcium ions included in atorvastatin molecule induced mitochondrial uncoupling that enhanced the inhibition of the mitochondrial respiratory chain by atorvastatin. Our results indicate that hydrophobic calcium-containing atorvastatin, widely used as anti-atherosclerotic agent, has a direct negative action on isolated endothelial mitochondria. Copyright © 2017. Published by Elsevier Inc.

Structural dynamics of the cell nucleus

PubMed Central

Wiegert, Simon; Bading, Hilmar

2011-01-01

Neuronal morphology plays an essential role in signal processing in the brain. Individual neurons can undergo use-dependent changes in their shape and connectivity, which affects how intracellular processes are regulated and how signals are transferred from one cell to another in a neuronal network. Calcium is one of the most important intracellular second messengers regulating cellular morphologies and functions. In neurons, intracellular calcium levels are controlled by ion channels in the plasma membrane such as NMDA receptors (NMDARs), voltage-gated calcium channels (VGCCs) and certain α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as well as by calcium exchange pathways between the cytosol and internal calcium stores including the endoplasmic reticulum and mitochondria. Synaptic activity and the subsequent opening of ligand and/or voltage-gated calcium channels can initiate cytosolic calcium transients which propagate towards the cell soma and enter the nucleus via its nuclear pore complexes (NPCs) embedded in the nuclear envelope. We recently described the discovery that in hippocampal neurons the morphology of the nucleus affects the calcium dynamics within the nucleus. Here we propose that nuclear infoldings determine whether a nucleus functions as an integrator or detector of oscillating calcium signals. We outline possible ties between nuclear mophology and transcriptional activity and discuss the importance of extending the approach to whole cell calcium signal modeling in order to understand synapse-to-nucleus communication in healthy and dysfunctional neurons. PMID:21738832

PeakCaller: an automated graphical interface for the quantification of intracellular calcium obtained by high-content screening.

PubMed

Artimovich, Elena; Jackson, Russell K; Kilander, Michaela B C; Lin, Yu-Chih; Nestor, Michael W

2017-10-16

Intracellular calcium is an important ion involved in the regulation and modulation of many neuronal functions. From regulating cell cycle and proliferation to initiating signaling cascades and regulating presynaptic neurotransmitter release, the concentration and timing of calcium activity governs the function and fate of neurons. Changes in calcium transients can be used in high-throughput screening applications as a basic measure of neuronal maturity, especially in developing or immature neuronal cultures derived from stem cells. Using human induced pluripotent stem cell derived neurons and dissociated mouse cortical neurons combined with the calcium indicator Fluo-4, we demonstrate that PeakCaller reduces type I and type II error in automated peak calling when compared to the oft-used PeakFinder algorithm under both basal and pharmacologically induced conditions. Here we describe PeakCaller, a novel MATLAB script and graphical user interface for the quantification of intracellular calcium transients in neuronal cultures. PeakCaller allows the user to set peak parameters and smoothing algorithms to best fit their data set. This new analysis script will allow for automation of calcium measurements and is a powerful software tool for researchers interested in high-throughput measurements of intracellular calcium.

Skin Barrier and Calcium.

PubMed

Lee, Sang Eun; Lee, Seung Hun

2018-06-01

Epidermal barrier formation and the maintenance of barrier homeostasis are essential to protect us from the external environments and organisms. Moreover, impaired keratinocytes differentiation and dysfunctional skin barrier can be the primary causes or aggravating factors for many inflammatory skin diseases including atopic dermatitis and psoriasis. Therefore, understanding the regulation mechanisms of keratinocytes differentiation and skin barrier homeostasis is important to understand many skin diseases and establish an effective treatment strategy. Calcium ions (Ca 2+ ) and their concentration gradient in the epidermis are essential in regulating many skin functions, including keratinocyte differentiation, skin barrier formation, and permeability barrier homeostasis. Recent studies have suggested that the intracellular Ca 2+ stores such as the endoplasmic reticulum (ER) are the major components that form the epidermal calcium gradient and the ER calcium homeostasis is crucial for regulating keratinocytes differentiation, intercellular junction formation, antimicrobial barrier, and permeability barrier homeostasis. Thus, both Ca 2+ release from intracellular stores, such as the ER and Ca 2+ influx mechanisms are important in skin barrier. In addition, growing evidences identified the functional existence and the role of many types of calcium channels which mediate calcium flux in keratinocytes. In this review, the origin of epidermal calcium gradient and their role in the formation and regulation of skin barrier are focused. We also focus on the role of ER calcium homeostasis in skin barrier. Furthermore, the distribution and role of epidermal calcium channels, including transient receptor potential channels, store-operated calcium entry channel Orai1, and voltage-gated calcium channels in skin barrier are discussed.

Structural dynamics of the cell nucleus: basis for morphology modulation of nuclear calcium signaling and gene transcription.

PubMed

Queisser, Gillian; Wiegert, Simon; Bading, Hilmar

2011-01-01

Neuronal morphology plays an essential role in signal processing in the brain. Individual neurons can undergo use-dependent changes in their shape and connectivity, which affects how intracellular processes are regulated and how signals are transferred from one cell to another in a neuronal network. Calcium is one of the most important intracellular second messengers regulating cellular morphologies and functions. In neurons, intracellular calcium levels are controlled by ion channels in the plasma membrane such as NMDA receptors (NMDARs), voltage-gated calcium channels (VGCCs) and certain α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as well as by calcium exchange pathways between the cytosol and internal calcium stores including the endoplasmic reticulum and mitochondria. Synaptic activity and the subsequent opening of ligand and/or voltage-gated calcium channels can initiate cytosolic calcium transients which propagate towards the cell soma and enter the nucleus via its nuclear pore complexes (NPCs) embedded in the nuclear envelope. We recently described the discovery that in hippocampal neurons the morphology of the nucleus affects the calcium dynamics within the nucleus. Here we propose that nuclear infoldings determine whether a nucleus functions as an integrator or detector of oscillating calcium signals. We outline possible ties between nuclear mophology and transcriptional activity and discuss the importance of extending the approach to whole cell calcium signal modeling in order to understand synapse-to-nucleus communication in healthy and dysfunctional neurons.

How does calcium interact with the cytoskeleton to regulate growth cone motility during axon pathfinding?

PubMed

Gasperini, Robert J; Pavez, Macarena; Thompson, Adrian C; Mitchell, Camilla B; Hardy, Holly; Young, Kaylene M; Chilton, John K; Foa, Lisa

2017-10-01

The precision with which neurons form connections is crucial for the normal development and function of the nervous system. The development of neuronal circuitry in the nervous system is accomplished by axon pathfinding: a process where growth cones guide axons through the embryonic environment to connect with their appropriate synaptic partners to form functional circuits. Despite intense efforts over many years to understand how this process is regulated, the complete repertoire of molecular mechanisms that govern the growth cone cytoskeleton and hence motility, remain unresolved. A central tenet in the axon guidance field is that calcium signals regulate growth cone behaviours such as extension, turning and pausing by regulating rearrangements of the growth cone cytoskeleton. Here, we provide evidence that not only the amplitude of a calcium signal is critical for growth cone motility but also the source of calcium mobilisation. We provide an example of this idea by demonstrating that manipulation of calcium signalling via L-type voltage gated calcium channels can perturb sensory neuron motility towards a source of netrin-1. Understanding how calcium signals can be transduced to initiate cytoskeletal changes represents a significant gap in our current knowledge of the mechanisms that govern axon guidance, and consequently the formation of functional neural circuits in the developing nervous system. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Simultaneous mapping of membrane voltage and calcium in zebrafish heart in vivo reveals chamber-specific developmental transitions in ionic currents

PubMed Central

Hou, Jennifer H.; Kralj, Joel M.; Douglass, Adam D.; Engert, Florian; Cohen, Adam E.

2014-01-01

The cardiac action potential (AP) and the consequent cytosolic Ca2+ transient are key indicators of cardiac function. Natural developmental processes, as well as many drugs and pathologies change the waveform, propagation, or variability (between cells or over time) of these parameters. Here we apply a genetically encoded dual-function calcium and voltage reporter (CaViar) to study the development of the zebrafish heart in vivo between 1.5 and 4 days post fertilization (dpf). We developed a high-sensitivity spinning disk confocal microscope and associated software for simultaneous three-dimensional optical mapping of voltage and calcium. We produced a transgenic zebrafish line expressing CaViar under control of the heart-specific cmlc2 promoter, and applied ion channel blockers at a series of developmental stages to map the maturation of the action potential in vivo. Early in development, the AP initiated via a calcium current through L-type calcium channels. Between 90 and 102 h post fertilization (hpf), the ventricular AP switched to a sodium-driven upswing, while the atrial AP remained calcium driven. In the adult zebrafish heart, a sodium current drives the AP in both the atrium and ventricle. Simultaneous voltage and calcium imaging with genetically encoded reporters provides a new approach for monitoring cardiac development, and the effects of drugs on cardiac function. PMID:25309445

Simultaneous mapping of membrane voltage and calcium in zebrafish heart in vivo reveals chamber-specific developmental transitions in ionic currents.

PubMed

Hou, Jennifer H; Kralj, Joel M; Douglass, Adam D; Engert, Florian; Cohen, Adam E

2014-01-01

The cardiac action potential (AP) and the consequent cytosolic Ca(2+) transient are key indicators of cardiac function. Natural developmental processes, as well as many drugs and pathologies change the waveform, propagation, or variability (between cells or over time) of these parameters. Here we apply a genetically encoded dual-function calcium and voltage reporter (CaViar) to study the development of the zebrafish heart in vivo between 1.5 and 4 days post fertilization (dpf). We developed a high-sensitivity spinning disk confocal microscope and associated software for simultaneous three-dimensional optical mapping of voltage and calcium. We produced a transgenic zebrafish line expressing CaViar under control of the heart-specific cmlc2 promoter, and applied ion channel blockers at a series of developmental stages to map the maturation of the action potential in vivo. Early in development, the AP initiated via a calcium current through L-type calcium channels. Between 90 and 102 h post fertilization (hpf), the ventricular AP switched to a sodium-driven upswing, while the atrial AP remained calcium driven. In the adult zebrafish heart, a sodium current drives the AP in both the atrium and ventricle. Simultaneous voltage and calcium imaging with genetically encoded reporters provides a new approach for monitoring cardiac development, and the effects of drugs on cardiac function.

Canonical Transient Receptor Potential Channel 2 (TRPC2) as a Major Regulator of Calcium Homeostasis in Rat Thyroid FRTL-5 Cells

PubMed Central

Sukumaran, Pramod; Löf, Christoffer; Kemppainen, Kati; Kankaanpää, Pasi; Pulli, Ilari; Näsman, Johnny; Viitanen, Tero; Törnquist, Kid

2012-01-01

Mammalian non-selective transient receptor potential cation channels (TRPCs) are important in the regulation of cellular calcium homeostasis. In thyroid cells, including rat thyroid FRTL-5 cells, calcium regulates a multitude of processes. RT-PCR screening of FRTL-5 cells revealed the presence of TRPC2 channels only. Knockdown of TRPC2 using shRNA (shTRPC2) resulted in decreased ATP-evoked calcium peak amplitude and inward current. In calcium-free buffer, there was no difference in the ATP-evoked calcium peak amplitude between control cells and shTRPC2 cells. Store-operated calcium entry was indistinguishable between the two cell lines. Basal calcium entry was enhanced in shTRPC2 cells, whereas the level of PKCβ1 and PKCδ, the activity of sarco/endoplasmic reticulum Ca2+-ATPase, and the calcium content in the endoplasmic reticulum were decreased. Stromal interaction molecule (STIM) 2, but not STIM1, was arranged in puncta in resting shTRPC2 cells but not in control cells. Phosphorylation site Orai1 S27A/S30A mutant and non-functional Orai1 R91W attenuated basal calcium entry in shTRPC2 cells. Knockdown of PKCδ with siRNA increased STIM2 punctum formation and enhanced basal calcium entry but decreased sarco/endoplasmic reticulum Ca2+-ATPase activity in wild-type cells. Transfection of a truncated, non-conducting mutant of TRPC2 evoked similar results. Thus, TRPC2 functions as a major regulator of calcium homeostasis in rat thyroid cells. PMID:23144458

Growth hormone secretagogues prevent dysregulation of skeletal muscle calcium homeostasis in a rat model of cisplatin-induced cachexia.

PubMed

Conte, Elena; Camerino, Giulia Maria; Mele, Antonietta; De Bellis, Michela; Pierno, Sabata; Rana, Francesco; Fonzino, Adriano; Caloiero, Roberta; Rizzi, Laura; Bresciani, Elena; Ben Haj Salah, Khoubaib; Fehrentz, Jean-Alain; Martinez, Jean; Giustino, Arcangela; Mariggiò, Maria Addolorata; Coluccia, Mauro; Tricarico, Domenico; Lograno, Marcello Diego; De Luca, Annamaria; Torsello, Antonio; Conte, Diana; Liantonio, Antonella

2017-06-01

Cachexia is a wasting condition associated with cancer types and, at the same time, is a serious and dose-limiting side effect of cancer chemotherapy. Skeletal muscle loss is one of the main characteristics of cachexia that significantly contributes to the functional muscle impairment. Calcium-dependent signaling pathways are believed to play an important role in skeletal muscle decline observed in cachexia, but whether intracellular calcium homeostasis is affected in this situation remains uncertain. Growth hormone secretagogues (GHS), a family of synthetic agonists of ghrelin receptor (GHS-R1a), are being developed as a therapeutic option for cancer cachexia syndrome; however, the exact mechanism by which GHS interfere with skeletal muscle is not fully understood. By a multidisciplinary approach ranging from cytofluorometry and electrophysiology to gene expression and histology, we characterized the calcium homeostasis in fast-twitch extensor digitorum longus (EDL) muscle of adult rats with cisplatin-induced cachexia and established the potential beneficial effects of two GHS (hexarelin and JMV2894) at this level. Additionally, in vivo measures of grip strength and of ultrasonography recordings allowed us to evaluate the functional impact of GHS therapeutic intervention. Cisplatin-treated EDL muscle fibres were characterized by a ~18% significant reduction of the muscle weight and fibre diameter together with an up-regulation of atrogin1/Murf-1 genes and a down-regulation of Pgc1-a gene, all indexes of muscle atrophy, and by a two-fold increase in resting intracellular calcium, [Ca 2+ ] i , compared with control rats. Moreover, the amplitude of the calcium transient induced by caffeine or depolarizing high potassium solution as well as the store-operated calcium entry were ~50% significantly reduced in cisplatin-treated rats. Calcium homeostasis dysregulation parallels with changes of functional ex vivo (excitability and resting macroscopic conductance) and in vivo (forelimb force and muscle volume) outcomes in cachectic animals. Administration of hexarelin or JMV2894 markedly reduced the cisplatin-induced alteration of calcium homeostasis by both common as well as drug-specific mechanisms of action. This effect correlated with muscle function preservation as well as amelioration of various atrophic indexes, thus supporting the functional impact of GHS activity on calcium homeostasis. Our findings provide a direct evidence that a dysregulation of calcium homeostasis plays a key role in cisplatin-induced model of cachexia gaining insight into the etiopathogenesis of this form of muscle wasting. Furthermore, our demonstration that GHS administration efficaciously prevents cisplatin-induced calcium homeostasis alteration contributes to elucidate the mechanism of action through which GHS could potentially ameliorate chemotherapy-associated cachexia. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

Calcification of the mitral valve and annulus: systematic evaluation of effects on valve anatomy and function.

PubMed

Movva, Rajesh; Murthy, Kinnari; Romero-Corral, Abel; Seetha Rammohan, Harish Raj; Fumo, Peter; Pressman, Gregg S

2013-10-01

Mitral annular calcification (MAC) is common in chronic kidney disease. It is associated with cardiovascular events and can cause valvular dysfunction, but it has not been systematically characterized. The aim of this prospective study was to assess the prevalence and distribution of MAC, its effects on leaflet motion, and its association with mitral stenosis and mitral regurgitation (MR) in a hemodialysis population. Echocardiograms were obtained in 75 consecutive hemodialysis outpatients. MAC extent and distribution were graded semiquantitatively using two-dimensional and three-dimensional echocardiography. Associations with the presence and severity of mitral stenosis and MR were explored. The mean age was 60 ± 14 years; 60% were men, and 87% were African American. MAC was present in 64% (moderate to severe in 48%). Calcium extended more than halfway onto the leaflet in 37% and beyond the annulus in 40%. Leaflet motion was restricted in 37%. Mitral stenosis was present in 28%, and the extent of calcification was associated with mean mitral valve gradient (P < .0001). MR was prevalent (present in 81%) but was severe in none. The severity of MAC was greater in patients with moderate MR than in those with no or mild MR (P = .04). Three-dimensional analysis suggested an uneven distribution of annular calcium; the middle and lateral anterior segments were less often calcified than the anterior-medial or posterior segments. Calcification in any annular segment was highly associated with restricted motion of the attached leaflet segment. MAC is common and often extensive in hemodialysis patients. Calcium may be unevenly distributed among the annular segments. When present, annular calcification reduces the angle of leaflet opening and can cause valvular dysfunction. Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

Structure-function of proteins interacting with the α1 pore-forming subunit of high-voltage-activated calcium channels

PubMed Central

Neely, Alan; Hidalgo, Patricia

2014-01-01

Openings of high-voltage-activated (HVA) calcium channels lead to a transient increase in calcium concentration that in turn activate a plethora of cellular functions, including muscle contraction, secretion and gene transcription. To coordinate all these responses calcium channels form supramolecular assemblies containing effectors and regulatory proteins that couple calcium influx to the downstream signal cascades and to feedback elements. According to the original biochemical characterization of skeletal muscle Dihydropyridine receptors, HVA calcium channels are multi-subunit protein complexes consisting of a pore-forming subunit (α1) associated with four additional polypeptide chains β, α2, δ, and γ, often referred to as accessory subunits. Twenty-five years after the first purification of a high-voltage calcium channel, the concept of a flexible stoichiometry to expand the repertoire of mechanisms that regulate calcium channel influx has emerged. Several other proteins have been identified that associate directly with the α1-subunit, including calmodulin and multiple members of the small and large GTPase family. Some of these proteins only interact with a subset of α1-subunits and during specific stages of biogenesis. More strikingly, most of the α1-subunit interacting proteins, such as the β-subunit and small GTPases, regulate both gating and trafficking through a variety of mechanisms. Modulation of channel activity covers almost all biophysical properties of the channel. Likewise, regulation of the number of channels in the plasma membrane is performed by altering the release of the α1-subunit from the endoplasmic reticulum, by reducing its degradation or enhancing its recycling back to the cell surface. In this review, we discuss the structural basis, interplay and functional role of selected proteins that interact with the central pore-forming subunit of HVA calcium channels. PMID:24917826

New Structural and Functional Contexts of the Dx[DN]xDG Linear Motif: Insights into Evolution of Calcium-Binding Proteins

PubMed Central

Rigden, Daniel J.; Woodhead, Duncan D.; Wong, Prudence W. H.; Galperin, Michael Y.

2011-01-01

Binding of calcium ions (Ca2+) to proteins can have profound effects on their structure and function. Common roles of calcium binding include structure stabilization and regulation of activity. It is known that diverse families – EF-hands being one of at least twelve – use a Dx[DN]xDG linear motif to bind calcium in near-identical fashion. Here, four novel structural contexts for the motif are described. Existing experimental data for one of them, a thermophilic archaeal subtilisin, demonstrate for the first time a role for Dx[DN]xDG-bound calcium in protein folding. An integrin-like embedding of the motif in the blade of a β-propeller fold – here named the calcium blade – is discovered in structures of bacterial and fungal proteins. Furthermore, sensitive database searches suggest a common origin for the calcium blade in β-propeller structures of different sizes and a pan-kingdom distribution of these proteins. Factors favouring the multiple convergent evolution of the motif appear to include its general Asp-richness, the regular spacing of the Asp residues and the fact that change of Asp into Gly and vice versa can occur though a single nucleotide change. Among the known structural contexts for the Dx[DN]xDG motif, only the calcium blade and the EF-hand are currently found intracellularly in large numbers, perhaps because the higher extracellular concentration of Ca2+ allows for easier fixing of newly evolved motifs that have acquired useful functions. The analysis presented here will inform ongoing efforts toward prediction of similar calcium-binding motifs from sequence information alone. PMID:21720552

Functional and pharmacological consequences of the distribution of voltage-gated calcium channels in the renal blood vessels.

PubMed

Hansen, P B L

2013-04-01

Calcium channel blockers are widely used to treat hypertension because they inhibit voltage-gated calcium channels that mediate transmembrane calcium influx in, for example, vascular smooth muscle and cardiomyocytes. The calcium channel family consists of several subfamilies, of which the L-type is usually associated with vascular contractility. However, the L-, T- and P-/Q-types of calcium channels are present in the renal vasculature and are differentially involved in controlling vascular contractility, thereby contributing to regulation of kidney function and blood pressure. In the preglomerular vascular bed, all the three channel families are present. However, the T-type channel is the only channel in cortical efferent arterioles which is in contrast to the juxtamedullary efferent arteriole, and that leads to diverse functional effects of L- and T-type channel inhibition. Furthermore, by different mechanisms, T-type channels may contribute to both constriction and dilation of the arterioles. Finally, P-/Q-type channels are involved in the regulation of human intrarenal arterial contractility. The calcium blockers used in the clinic affect not only L-type but also P-/Q- and T-type channels. Therefore, the distinct effect obtained by inhibiting a given subtype or set of channels under experimental settings should be considered when choosing a calcium blocker for treatment. T-type channels seem to be crucial for regulating the GFR and the filtration fraction. Use of blockers is expected to lead to preferential efferent vasodilation, reduction of glomerular pressure and proteinuria. Therefore, renovascular T-type channels might provide novel therapeutic targets, and may have superior renoprotective effects compared to conventional calcium blockers. Acta Physiologica © 2013 Scandinavian Physiological Society.

[Content of mineral elements in the diet of students of physical education faculty].

PubMed

Novokshanova, A L; Nikitiyk, D B; Pozdniakov, A L

2013-01-01

Research of the diet of students of the Faculty of Physical Education found discrepancy of caloric content and correlation of macro- and micronutrients to physiological norms accompanied by a deficiency of some mineral elements. Thus, this research found discrepancy of a diet in caloric content and correlation of macro- and micronutrients to physiological norms. Calorie deficiency in both groups is caused for lack of all macro- and micronutrients, but mostly for lack of carbohydrates with an average glycemic index, fruit, and vegetables that have prebiotic properties and mineral-rich elements. Deficiency in the diet of young men 9.6% of the total protein and 23.5% of carbohydrates was accompanied for lack 15.5% of calcium. In the group of girls the results showed a decrease of the required amounts of calcium, magnesium and iron of 36.4; 7.5 and 1.5% respectively, which was displayed against a background of reducing the consumption of the total protein 25.1 and 36.0% of carbohydrates. As a result, basic nutrition of students practicing sports requires rationalization and adjustment. To improve the biological value of the diet it is advisable for students to use daily dairy products and other sources of animal protein in their diets. It is also necessary to introduce fruit and vegetables as a source of dietary fibers and mineral elements. Created in both groups deficiency of calcium and biologically high-grade proteins of animal origin can be eliminated by various dairy products in which calcium and phosphorus are in easily digestible form and in a balanced quantity. Despite the considerable amount of calcium in many foods (meat, bread, cereals, vegetables) calcium is assimilated with difficulty from these products. The exception is the calcium of milk, curd, cheese and other dairy products. The ration between calcium and phosphorus in milk is 1:1-1.4:1. For example, taking 0.5 liters of milk provides 600 mg of assimilable calcium intake.

Bioaccessibility of four calcium sources in different whey-based dairy matrices assessed by in vitro digestion.

PubMed

Lorieau, Lucie; Le Roux, Linda; Gaucheron, Frédéric; Ligneul, Amandine; Hazart, Etienne; Dupont, Didier; Floury, Juliane

2018-04-15

Numerous calcium sources are available to enrich food, but their behavior during digestion is still unknown. This study focused on the influence of the gastro-intestinal pH, the food structure and the calcium source on the bioaccessibility of the nutrient. Four calcium sources were studied: calcium carbonate, calcium citrate malate, calcium phosphate and calcium bisglycinate. These were added to dairy matrices, containing cream and whey proteins, of different forms (liquid or gel). The kinetics of solubility and ionic calcium concentration during in vitro digestion were studied, as function of gastro-intestinal pH. All calcium sources were almost fully soluble in the gastric compartment, and then became insoluble in the intestinal phase. The level of calcium insolubilisation in the intestinal phase was not significantly influenced by the matrix structure (liquid or gel), but was more dependent on the calcium source, this effect leading to different final calcium bioaccessibility from 36% to 20%. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effect of habitat geology on calcium intake and calcium status of wild rodents.

PubMed

Shore, R F; Balment, R J; Yalden, D W

1991-12-01

Calcium is essential for normal physiological function, reproduction and growth in mammals but its distribution in the natural environment is heterogeneous. Spatial variation in calcium soil content is especially marked in the Peak District, United Kingdom, where both calcium-rich limestone and calcium-poor gritstone rock types occur. Wood mice Apodemus sylvaticus (L) and bank voles Clethrionomys glareolus (Schreber 1780) from limestone areas had significantly higher calcium concentrations in stomach contents and in faeces compared with their counterparts from gritstone areas. Calcium status was assessed from serum calcium concentration, femur weight, ash content of the body, calcium concentration in the femur and body ash. There was no significant difference in serum calcium concentration, femur calcium concentration and body ash calcium concentration between animals from the limestone and the gritstone. However, on the limestone, bank voles, but not wood mice, had significantly heavier femora and a greater proportion of ash in the body compared with their gritstone counterparts.

Mechanisms of pyrethroid insecticide-induced stimulation of calcium influx in neocortical neurons

EPA Science Inventory

Pyrethroid insecticides bind to voltage-gated sodium channels (VGSCs) and modify their gating kinetics, thereby disrupting neuronal function. Pyrethroids have also been reported to alter the function of other channel types, including activation of voltage-gated Ca2+ calcium chann...

Altered sarco(endo)plasmic reticulum calcium adenosine triphosphatase 2a content: Targets for heart failure therapy.

PubMed

Liu, Gang; Li, Si Qi; Hu, Ping Ping; Tong, Xiao Yong

2018-05-01

Sarco(endo)plasmic reticulum calcium adenosine triphosphatase is responsible for transporting cytosolic calcium into the sarcoplasmic reticulum and endoplasmic reticulum to maintain calcium homeostasis. Sarco(endo)plasmic reticulum calcium adenosine triphosphatase is the dominant isoform expressed in cardiac tissue, which is regulated by endogenous protein inhibitors, post-translational modifications, hormones as well as microRNAs. Dysfunction of sarco(endo)plasmic reticulum calcium adenosine triphosphatase is associated with heart failure, which makes sarco(endo)plasmic reticulum calcium adenosine triphosphatase a promising target for heart failure therapy. This review summarizes current approaches to ameliorate sarco(endo)plasmic reticulum calcium adenosine triphosphatase function and focuses on phospholamban, an endogenous inhibitor of sarco(endo)plasmic reticulum calcium adenosine triphosphatase, pharmacological tools and gene therapies.

A quadruped study on chitosan microspheres containing atorvastatin calcium: preparation, characterization, quantification and in-vivo application.

PubMed

Eroglu, Hakan; Nemutlu, Emirhan; Turkoglu, Omer Faruk; Nacar, Osman; Bodur, Ebru; Sargon, Mustafa Fevzi; Beskonakli, Etem; Oner, Levent

2010-09-01

Atorvastatin is commonly used as a cholesterol lowering agent in patients. Recently, the neuroprotective effects of atorvastatin became the focus of many research studies. In this study, we have formulated chitosan microspheres containing atorvastatin calcium. In-vitro characterization of chitosan microspheres and quantification of atorvastatin calcium from formulations were also evaluated. The neuroprotective efficiency of atorvastatin calcium was investigated by an experimental spinal cord injury model. Atorvastatin calcium microspheres were implanted at the laminectomy area (1 mg/kg) immediately after trauma. Twenty-four hours after injury, motor functions of animals were scored according to modified Tarlov Scale. In spinal cord tissues tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and lipid peroxidation levels were quantified and ultrastructural changes have been investigated. The results of all parameters indicate that microspheres containing atorvastatin calcium were capable of improving functional outcome, attenuating the expression of TNF-alpha, IL-1beta and IL-6; lowering lipid peroxidation levels and maintaining the preservation of the cellular uniformity.

Calcium citrate without aluminum antacids does not cause aluminum retention in patients with functioning kidneys

NASA Technical Reports Server (NTRS)

Sakhaee, K.; Wabner, C. L.; Zerwekh, J. E.; Copley, J. B.; Pak, L.; Poindexter, J. R.; Pak, C. Y.

1993-01-01

It has been suggested that calcium citrate might enhance aluminum absorption from food, posing a threat of aluminum toxicity even in patients with normal renal function. We therefore measured serum and urinary aluminum before and following calcium citrate therapy in patients with moderate renal failure and in normal subjects maintained on constant metabolic diets with known aluminum content (967-1034 mumol/day, or 26.1-27.9 mg/day, in patients and either 834 or 1579 mumol/day, or 22.5 and 42.6 mg/day, in normal subjects). Seven patients with moderate renal failure (endogenous creatinine clearance of 43 ml/min) took 50 mmol (2 g) calcium/day as effervescent calcium citrate with meals for 17 days. Eight normal women received 25 mmol (1 g) calcium/day as tricalcium dicitrate tablets with meals for 7 days. In patients with moderate renal failure, serum and urinary aluminum were normal before treatment at 489 +/- 293 SD nmol/l (13.2 +/- 7.9 micrograms/l) and 767 +/- 497 nmol/day (20.7 +/- 13.4 micrograms/day), respectively. They remained within normal limits and did not change significantly during calcium citrate treatment (400 +/- 148 nmol/l and 600 +/- 441 nmol/day, respectively). Similarly, no significant change in serum and urinary aluminum was detected in normal women during calcium citrate administration (271 +/- 59 vs 293 +/- 85 nmol/l and 515 +/- 138 vs 615 +/- 170 nmol/day, respectively). In addition, skeletal bone aluminum content did not change significantly in 14 osteoporotic patients (endogenous creatinine clearance of 68.5 ml/min) treated for 24 months with calcium citrate, 10 mmol calcium twice/day separately from meals (29.3 +/- 13.9 ng/mg ash bone to 27.9 +/0- 10.4, P = 0.727). In them, histomorphometric examination did not show any evidence of mineralization defect. Thus, calcium citrate given alone without aluminum-containing drugs does not pose a risk of aluminum toxicity in subjects with normal or functioning kidneys, when it is administered on an empty stomach at a recommended dose of 20 mmol calcium/day.

Voltage-Gated Calcium Channels

NASA Astrophysics Data System (ADS)

Zamponi, Gerald Werner

Voltage Gated Calcium Channels is the first comprehensive book in the calcium channel field, encompassing over thirty years of progress towards our understanding of calcium channel structure, function, regulation, physiology, pharmacology, and genetics. This book balances contributions from many of the leading authorities in the calcium channel field with fresh perspectives from risings stars in the area, taking into account the most recent literature and concepts. This is the only all-encompassing calcium channel book currently available, and is an essential resource for academic researchers at all levels in the areas neuroscience, biophysics, and cardiovascular sciences, as well as to researchers in the drug discovery area.

[Cognitive Function and Calcium. Structures and functions of Ca2+-permeable channels].

PubMed

Kaneko, Shuji

2015-02-01

Calcium is essential for living organisms where the increase in intracellular Ca2+ concentration functions as a second messenger for many cellular processes including synaptic transmission and neural plasticity. The cytosolic concentration of Ca2+ is finely controlled by many Ca2+-permeable ion channels and transporters. The comprehensive view of their expression, function, and regulation will advance our understanding of neural and cognitive functions of Ca2+, which leads to the future drug discovery.

Paradoxical expression of E-cadherin in prostatic bone metastases.

PubMed

Bryden, A A; Freemont, A J; Clarke, N W; George, N J

1999-12-01

To determine whether the calcium-dependent cell adhesion molecule E-cadherin is expressed in metastatic deposits of prostate cancer in bone. Ten bone biopsies containing metastatic deposits of untreated prostatic cancer were obtained and immunohistochemically stained for E-cadherin with the monoclonal antibody HECD-1, using the streptavidin-biotin complex technique. Benign prostatic tissue was used as the control. Of the 10 specimens, nine showed positive expression of E-cadherin, graded as strong in four. E-cadherin expression was strongest in well-differentiated metastases and decreased with increasing tumour grade. In some specimens there were mixed patterns of expression. E-cadherin is strongly expressed in prostatic bone metastases and the degree of expression appears to reflect local tumour grade. This suggests that loss of E-cadherin expression may not be critically linked to metastatic potential.

Function of endoplasmic reticulum calcium ATPase in innate immunity-mediated programmed cell death

PubMed Central

Zhu, Xiaohong; Caplan, Jeffrey; Mamillapalli, Padmavathi; Czymmek, Kirk; Dinesh-Kumar, Savithramma P

2010-01-01

Programmed cell death (PCD) initiated at the pathogen-infected sites during the plant innate immune response is thought to prevent the development of disease. Here, we describe the identification and characterization of an ER-localized type IIB Ca2+-ATPase (NbCA1) that function as a regulator of PCD. Silencing of NbCA1 accelerates viral immune receptor N- and fungal-immune receptor Cf9-mediated PCD, as well as non-host pathogen Pseudomonas syringae pv. tomato DC3000 and the general elicitor cryptogein-induced cell death. The accelerated PCD rescues loss-of-resistance phenotype of Rar1, HSP90-silenced plants, but not SGT1-silenced plants. Using a genetically encoded calcium sensor, we show that downregulation of NbCA1 results in the modulation of intracellular calcium signalling in response to cryptogein elicitor. We further show that NbCAM1 and NbrbohB function as downstream calcium decoders in N-immune receptor-mediated PCD. Our results indicate that ER-Ca2+-ATPase is a component of the calcium efflux pathway that controls PCD during an innate immune response. PMID:20075858

Characterization of calcium oxalate defective (cod) 3 mutant from Medicago truncatula

USDA-ARS?s Scientific Manuscript database

Many plants invest a considerable amount of resources and energy into the formation of calcium oxalate crystals. Assigned roles for plant crystal formation include functions in defense, calcium regulation, and aluminum tolerance. From a human health standpoint, oxalate present in edible plant tiss...

Organic-inorganic Interface in Nacre: Learning Lessons from Nature

NASA Astrophysics Data System (ADS)

Rahbar, Nima; Askarinejad, Sina

Problem-solving strategies of naturally growing composites such as nacre give us a fantastic vision to design and fabricate tough, stiff while strong composites. To provide the outstanding mechanical functions, nature has evolved complex and effective functionally graded interfaces. Particularly in nacre, organic-inorganic interface in which the proteins behave stiffer and stronger in proximity of calcium carbonate minerals provide an impressive role in structural integrity and mechanical deformation of the natural composite. The well-known shear-lag theory was employed on a simplified two-dimensional unit-cell of the multilayered composite considering the interface properties. The closed-form solutions for the displacements in the elastic components as a function of constituent properties can be used to calculate the effective mechanical properties of composite such as elastic modulus, strength and work-to-failure. The results solve the important mysteries about nacre and emphasize on the role of organic-inorganic interface properties and mineral bridges. Our results show that the properties of proteins in proximity of mineral bridges are also significant. More studies need to be performed on the strategies to enhance the interface properties in manmade composites. NSF Career Award no. 1281264.

Diabetic Neuropathy: Mechanisms, Emerging Treatments, and Subtypes

PubMed Central

Pop-Busui, Rodica

2016-01-01

Diabetic neuropathies (DNs) differ in clinical course, distribution, fiber involvement (type and size), and pathophysiology, the most typical type being a length-dependent distal symmetric polyneuropathy (DSP) with differing degrees of autonomic involvement. The pathogenesis of diabetic DSP is multifactorial, including increased mitochondrial production of free radicals due to hyperglycemia-induced oxidative stress. Mechanisms that impact neuronal activity, mitochondrial function, membrane permeability, and endothelial function include formation of advanced glycosylation end products, activation of polyol aldose reductase signaling, activation of poly(ADP ribose) polymerase, and altered function of the Na+/K+-ATPase pump. Hyperglycemia-induced endoplasmic reticulum stress triggers several neuronal apoptotic processes. Additional mechanisms include impaired nerve perfusion, dyslipidemia, altered redox status, low-grade inflammation, and perturbation of calcium balance. Successful therapies require an integrated approach targeting these mechanisms. Intensive glycemic control is essential but is insufficient to prevent onset or progression of DSP, and disease-modifying treatments for DSP have been disappointing. Atypical forms of DN include subacute-onset sensory (symmetric) or motor (asymmetric) predominant conditions that are frequently painful but generally self-limited. DNs are a major cause of disability, associated with reduced quality of life and increased mortality. PMID:24954624

Advanced ceramic coating development for industrial/utility gas turbines

NASA Technical Reports Server (NTRS)

Vogan, J. W.; Stetson, A. R.

1982-01-01

A program was conducted with the objective of developing advanced thermal barrier coating (TBC) systems. Coating application was by plasma spray. Duplex, triplex and graded coatings were tested. Coating systems incorporated both NiCrAly and CoCrAly bond coats. Four ceramic overlays were tested: ZrO2.82O3; CaO.TiO2; 2CaO.SiO2; and MgO.Al2O3. The best overall results were obtained with a CaO.TiO2 coating applied to a NiCrAly bond coat. This coating was less sensitive than the ZrO2.8Y2O3 coating to process variables and part geometry. Testing with fuels contaminated with compounds containing sulfur, phosphorus and alkali metals showed the zirconia coatings were destabilized. The calcium titanate coatings were not affected by these contaminants. However, when fuels were used containing 50 ppm of vanadium and 150 ppm of magnesium, heavy deposits were formed on the test specimens and combustor components that required frequent cleaning of the test rig. During the program Mars engine first-stage turbine blades were coated and installed for an engine cyclic endurance run with the zirconia, calcium titanate, and calcium silicate coatings. Heavy spalling developed with the calcium silicate system. The zirconia and calcium titanate systems survived the full test duration. It was concluded that these two TBC's showed potential for application in gas turbines.

Growing Strong and Healthy with Mister Bone: An Educational Program to Have Strong Bones Later in Life

PubMed Central

Pampaloni, Barbara; Cianferotti, Luisella; Gronchi, Giorgio; Bartolini, Elisa; Fabbri, Sergio; Tanini, Annalisa; Brandi, Maria Luisa

2015-01-01

Optimal peak bone mass and bone health later in life are favored by a sufficient calcium intake in infancy, childhood and adolescence. The purpose of this study was to test a new educational program created to monitor and to improve calcium and vitamin D intake in children. Nutritional habits in children were evaluated through a food frequency questionnaire (FFQ) to assess the intake of calcium, vitamin D, dairy products, and total caloric energy at baseline and after seven months of exposure to a unique educational program applied between November 2013 and May 2014 in 176 schoolchildren (48% male, 52% female) attending the fourth and fifth grades of two selected primary schools in Florence, Italy. A significant increase of calcium (from 870 ± 190 to 1100 ± 200 mg/day, p < 0.05), and vitamin D (from 3.6 ± 1.53 to 4.1 ± 2 µg/day) intake in children was documented after the educational program. The amount of specific foods important for bone health consumed, such as milk and vegetables, increased significantly, both in male and female children (p < 0.05). The proposed educational program appears to be effective in modifying calcium intake in children, with a significant increase in the consumption of dairy products and vegetables, but without a significant change in the total caloric intake. PMID:26633485

Seminal Plasma pH, Inorganic Phosphate, Total and Ionized Calcium Concentrations In The Assessment of Human Spermatozoa Function.

PubMed

Banjoko, S Olatunbosun; Adeseolu, Fasiu O

2013-11-01

Fertilization in humans is dependent on viability of the male spermatozoa among other factors and there have been conflicting reports on the role of pH, calcium and phosphate concentrations in sperm function. This study therefore aimed to investigate seminal plasma pH, inorganic phosphate, total and ionized calcium concentrations relative to spermatozoa function. Seminal plasma concentrations of pH, total calcium, ionized calcium (Ca(++)); inorganic phosphate, motility and spermatozoa count were determined in 80 males by standard methods. Forty-nine of the subjects had normal spermatozoa motility (> 60%) and 31 had hypomotility (< 60%). The hypomotility group exhibited lower calcium ion (Ca(2)+) concentrations; 0.19+0.01mmol/L compared with normal motility group; 0.24+0.01mmol/L (p<0.001) the latter also had significantly higher inorganic phosphate; 7.83+1.27 while the former had 5.64+1.62mmol/L (p= 0.004). The mean spermatozoa counts for hypomotility and normal motility group were 42.0 ± 13 x 106 , 72.35 + 20 x 106 respectively (p< 0.001). No significant differences were observed in pH, volume of ejaculate and total calcium concentration between the hypomotility and normal motility groups The mean concentrations of pH were 7.51 ± 0.02 and 7.54 ± 0.03 respectively (p= 0.21) and total calcium; 3.10 ± 0.12 and 3.36 ± 0.14mmol/L respectively (p= 0.16 ). There was a significant difference in percentage of abnormal forms in both groups with hypomotile group having 36% compared to mormal motility group with 5% (p< 0.05). Correlations were observed between seminal concentrations of calcium ions, inorganic phosphate, spermatozoa count and motility but not with total calcium concentrations and pH and therefore should be considered in understanding male infertility and preparation of media for sperm preservation for in vitro fertilization.

Apoptosis-mediated endothelial toxicity but not direct calcification or functional changes in anti-calcification proteins defines pathogenic effects of calcium phosphate bions

NASA Astrophysics Data System (ADS)

Kutikhin, Anton G.; Velikanova, Elena A.; Mukhamadiyarov, Rinat A.; Glushkova, Tatiana V.; Borisov, Vadim V.; Matveeva, Vera G.; Antonova, Larisa V.; Filip'Ev, Dmitriy E.; Golovkin, Alexey S.; Shishkova, Daria K.; Burago, Andrey Yu.; Frolov, Alexey V.; Dolgov, Viktor Yu.; Efimova, Olga S.; Popova, Anna N.; Malysheva, Valentina Yu.; Vladimirov, Alexandr A.; Sozinov, Sergey A.; Ismagilov, Zinfer R.; Russakov, Dmitriy M.; Lomzov, Alexander A.; Pyshnyi, Dmitriy V.; Gutakovsky, Anton K.; Zhivodkov, Yuriy A.; Demidov, Evgeniy A.; Peltek, Sergey E.; Dolganyuk, Viatcheslav F.; Babich, Olga O.; Grigoriev, Evgeniy V.; Brusina, Elena B.; Barbarash, Olga L.; Yuzhalin, Arseniy E.

2016-06-01

Calcium phosphate bions (CPB) are biomimetic mineralo-organic nanoparticles which represent a physiological mechanism regulating the function, transport and disposal of calcium and phosphorus in the human body. We hypothesised that CPB may be pathogenic entities and even a cause of cardiovascular calcification. Here we revealed that CPB isolated from calcified atherosclerotic plaques and artificially synthesised CPB are morphologically and chemically indistinguishable entities. Their formation is accelerated along with the increase in calcium salts-phosphates/serum concentration ratio. Experiments in vitro and in vivo showed that pathogenic effects of CPB are defined by apoptosis-mediated endothelial toxicity but not by direct tissue calcification or functional changes in anti-calcification proteins. Since the factors underlying the formation of CPB and their pathogenic mechanism closely resemble those responsible for atherosclerosis development, further research in this direction may help us to uncover triggers of this disease.

Thermodynamics and Kinetics of Boron Removal from Metallurgical Grade Silicon by Addition of High Basic Potassium Carbonate to Calcium Silicate Slag

NASA Astrophysics Data System (ADS)

Wu, Jijun; Wang, Fanmao; Ma, Wenhui; Lei, Yun; Yang, Bin

2016-06-01

In this study, we investigated the thermodynamics and kinetics of boron removal from metallurgical grade silicon (MG-Si) using a calcium silicate slag containing a high basic potassium carbonate. The distribution of boron between slag and silicon was theoretically derived and the distribution coefficients ( L B) of boron with different compositions of CaO, SiO2, and K2CO3 in slag reagents were determined. The maximal value of L B reached 2.08 with a high basicity slag of 40 pctCaO-40 pctSiO2-20 pctK2CO3 (Λ = 0.73). The boron removal rates from MG-Si using CaO-SiO2 and CaO-SiO2-K2CO3 slags at 1823 K (1550 °C) were investigated in an electromagnetic induction furnace. The results showed that the boron concentration in MG-Si can be reduced from 22 to 1.8 ppmw at 1823 K (1550 °C) with 20 pct K2CO3 addition to calcium silicate slag, where the removal efficiency of boron reached 91.8 pct. The mass transfer coefficient ( β S) of boron in binary 50 pctCaO-50 pctSiO2 slag was 3.16 × 10-6 m s-1 at 1823 K (1550 °C) and was 2.43 × 10-5 m s-1 in ternary 40 pctCaO-40 pctSiO2-20 pctK2CO3 slag.

Calpain-1 knockout reveals broad effects on erythrocyte deformability and physiology

PubMed Central

Wieschhaus, Adam; Khan, Anwar; Zaidi, Asma; Rogalin, Henry; Hanada, Toshihiko; Liu, Fei; De Franceschi, Lucia; Brugnara, Carlo; Rivera, Alicia; Chishti, Athar H.

2014-01-01

Pharmacological inhibitors of cysteine proteases have provided useful insights into the regulation of calpain activity in erythrocytes. However, the precise biological function of calpain activity in erythrocytes remains poorly understood. Erythrocytes express calpain-1, an isoform regulated by calpastatin, the endogenous inhibitor of calpains. In the present study, we investigated the function of calpain-1 in mature erythrocytes using our calpain-1-null [KO (knockout)] mouse model. The calpain-1 gene deletion results in improved erythrocyte deformability without any measurable effect on erythrocyte lifespan in vivo. The calcium-induced sphero-echinocyte shape transition is compromised in the KO erythrocytes. Erythrocyte membrane proteins ankyrin, band 3, protein 4.1R, adducin and dematin are degraded in the calcium-loaded normal erythrocytes but not in the KO erythrocytes. In contrast, the integrity of spectrin and its state of phosphorylation are not affected in the calcium-loaded erythrocytes of either genotype. To assess the functional consequences of attenuated cytoskeletal remodelling in the KO erythrocytes, the activity of major membrane transporters was measured. The activity of the K+–Cl− co-transporter and the Gardos channel was significantly reduced in the KO erythrocytes. Similarly, the basal activity of the calcium pump was reduced in the absence of calmodulin in the KO erythrocyte membrane. Interestingly, the calmodulin-stimulated calcium pump activity was significantly elevated in the KO erythrocytes, implying a wider range of pump regulation by calcium and calmodulin. Taken together, and with the atomic force microscopy of the skeletal network, the results of the present study provide the first evidence for the physiological function of calpain-1 in erythrocytes with therapeutic implications for calcium imbalance pathologies such as sickle cell disease. PMID:22870887

Carotid Artery Stiffness, Digital Endothelial Function, and Coronary Calcium in Patients with Essential Thrombocytosis, Free of Overt Atherosclerotic Disease

PubMed Central

Vrtovec, Matjaz; Anzic, Ajda; Zupan, Irena Preloznik; Zaletel, Katja

2017-01-01

Abstract Background Patients with myeloproliferative neoplasms (MPNs) are at increased risk for atherothrombotic events. Our aim was to determine if patients with essential thrombocytosis (ET), a subtype of MPNs, free of symptomatic atherosclerosis, have greater carotid artery stiffness, worse endothelial function, greater coronary calcium and carotid plaque burden than control subjects. Patients and methods 40 ET patients without overt vascular disease, and 42 apparently healthy, age and sex-matched control subjects with comparable classical risk factors for atherosclerosis and Framingham risk of coronary disease were enrolled. All subjects were examined by physical and laboratory testing, carotid echo-tracking ultrasound, digital EndoPat pletysmography and CT coronary calcium scoring. Results No significant differences were found between ET patients and controls in carotid plaque score [1 (0-1.25) vs. 0 (0-2), p=0.30], β- index of carotid stiffness [7.75 (2.33) vs. 8.44 (2,81), p=0.23], pulse wave velocity [6,21 (1,00) vs. 6.45 (1.04) m/s; p=0.46], digital reactive hyperemia index [2.10 (0.57) vs. 2.35 (0.62), p=0.07], or augmentation index [19 (3-30) vs. 13 (5-22) %, p=0.38]. Overall coronary calcium burden did not differ between groups [Agatston score 0.1 (0-16.85) vs. 0 (0-8.55), p=0.26]. However, significantly more ET patients had an elevated coronary calcium score of >160 [6/40 vs. 0/42, p < 0.01]. Conclusions No significant differences between groups were found in carotid artery morphology and function, digital endothelial function or overall coronary calcium score. Significantly more ET patients had an elevated coronary calcium score of >160, indicating high cardiovascular risk, not predicted by the Framingham equation. PMID:28740456

Carotid Artery Stiffness, Digital Endothelial Function, and Coronary Calcium in Patients with Essential Thrombocytosis, Free of Overt Atherosclerotic Disease.

PubMed

Vrtovec, Matjaz; Anzic, Ajda; Zupan, Irena Preloznik; Zaletel, Katja; Blinc, Ales

2017-06-01

Patients with myeloproliferative neoplasms (MPNs) are at increased risk for atherothrombotic events. Our aim was to determine if patients with essential thrombocytosis (ET), a subtype of MPNs, free of symptomatic atherosclerosis, have greater carotid artery stiffness, worse endothelial function, greater coronary calcium and carotid plaque burden than control subjects. 40 ET patients without overt vascular disease, and 42 apparently healthy, age and sex-matched control subjects with comparable classical risk factors for atherosclerosis and Framingham risk of coronary disease were enrolled. All subjects were examined by physical and laboratory testing, carotid echo-tracking ultrasound, digital EndoPat pletysmography and CT coronary calcium scoring. No significant differences were found between ET patients and controls in carotid plaque score [1 (0-1.25) vs. 0 (0-2), p=0.30], β- index of carotid stiffness [7.75 (2.33) vs. 8.44 (2,81), p=0.23], pulse wave velocity [6,21 (1,00) vs. 6.45 (1.04) m/s; p=0.46], digital reactive hyperemia index [2.10 (0.57) vs. 2.35 (0.62), p=0.07], or augmentation index [19 (3-30) vs. 13 (5-22) %, p=0.38]. Overall coronary calcium burden did not differ between groups [Agatston score 0.1 (0-16.85) vs. 0 (0-8.55), p=0.26]. However, significantly more ET patients had an elevated coronary calcium score of >160 [6/40 vs. 0/42, p < 0.01]. No significant differences between groups were found in carotid artery morphology and function, digital endothelial function or overall coronary calcium score. Significantly more ET patients had an elevated coronary calcium score of >160, indicating high cardiovascular risk, not predicted by the Framingham equation.

Calpain-1 knockout reveals broad effects on erythrocyte deformability and physiology.

PubMed

Wieschhaus, Adam; Khan, Anwar; Zaidi, Asma; Rogalin, Henry; Hanada, Toshihiko; Liu, Fei; De Franceschi, Lucia; Brugnara, Carlo; Rivera, Alicia; Chishti, Athar H

2012-11-15

Pharmacological inhibitors of cysteine proteases have provided useful insights into the regulation of calpain activity in erythrocytes. However, the precise biological function of calpain activity in erythrocytes remains poorly understood. Erythrocytes express calpain-1, an isoform regulated by calpastatin, the endogenous inhibitor of calpains. In the present study, we investigated the function of calpain-1 in mature erythrocytes using our calpain-1-null [KO (knockout)] mouse model. The calpain-1 gene deletion results in improved erythrocyte deformability without any measurable effect on erythrocyte lifespan in vivo. The calcium-induced sphero-echinocyte shape transition is compromised in the KO erythrocytes. Erythrocyte membrane proteins ankyrin, band 3, protein 4.1R, adducin and dematin are degraded in the calcium-loaded normal erythrocytes but not in the KO erythrocytes. In contrast, the integrity of spectrin and its state of phosphorylation are not affected in the calcium-loaded erythrocytes of either genotype. To assess the functional consequences of attenuated cytoskeletal remodelling in the KO erythrocytes, the activity of major membrane transporters was measured. The activity of the K+-Cl- co-transporter and the Gardos channel was significantly reduced in the KO erythrocytes. Similarly, the basal activity of the calcium pump was reduced in the absence of calmodulin in the KO erythrocyte membrane. Interestingly, the calmodulin-stimulated calcium pump activity was significantly elevated in the KO erythrocytes, implying a wider range of pump regulation by calcium and calmodulin. Taken together, and with the atomic force microscopy of the skeletal network, the results of the present study provide the first evidence for the physiological function of calpain-1 in erythrocytes with therapeutic implications for calcium imbalance pathologies such as sickle cell disease.

Molecular imaging of in vivo calcium ion expression in area postrema of total sleep deprived rats: Implications for cardiovascular regulation by TOF-SIMS analysis

NASA Astrophysics Data System (ADS)

Mai, Fu-Der; Chen, Li-You; Ling, Yong-Chien; Chen, Bo-Jung; Wu, Un-In; Chang, Hung-Ming

2010-05-01

Excessive calcium influx in chemosensitive neurons of area postrema (AP) is detrimental for sympathetic activation and participates in the disruption of cardiovascular activities. Since total sleep deprivation (TSD) is a stressful condition known to harm the cardiovascular function, the present study is aimed to determine whether the in vivo calcium expression in AP would significantly alter following TSD by the use of time-of-flight secondary ion mass spectrometry (TOF-SIMS) and calretinin (a specific calcium sensor protein in AP neurons) immunohistochemistry. The results indicated that in normal rats, the calcium intensity was estimated to be 0.5 × 10 5 at m/ z 40.08. However, following TSD, the intensity for calcium ions was greatly increased to 1.2 × 10 5. Molecular imaging revealed that after TSD, various strongly expressed calcium signals were distributed throughout AP with clear identified profiles instead of randomly scattered within this region in normal rats. Immunohistochemical staining corresponded well with ionic image in which a majority of calcium-enriched gathering co-localized with calretinin positive neurons. The functional significance of TSD-induced calcium augmentation was demonstrated by increased heart rate and mean arterial pressure, clinical markers for cardiovascular dysfunction. Considering AP-mediated sympathetic activation is important for cardiovascular regulation, exaggerated calcium influx in AP would render this neurocircuitry more vulnerable to over-excitation, which might serve as the underlying mechanism for the development of TSD-relevant cardiovascular deficiency.

From contraction to gene expression: nanojunctions of the sarco/endoplasmic reticulum deliver site- and function-specific calcium signals.

PubMed

Evans, A Mark; Fameli, Nicola; Ogunbayo, Oluseye A; Duan, Jingxian; Navarro-Dorado, Jorge

2016-08-01

Calcium signals determine, for example, smooth muscle contraction and changes in gene expression. How calcium signals select for these processes is enigmatic. We build on the "panjunctional sarcoplasmic reticulum" hypothesis, describing our view that different calcium pumps and release channels, with different kinetics and affinities for calcium, are strategically positioned within nanojunctions of the SR and help demarcate their respective cytoplasmic nanodomains. SERCA2b and RyR1 are preferentially targeted to the sarcoplasmic reticulum (SR) proximal to the plasma membrane (PM), i.e., to the superficial buffer barrier formed by PM-SR nanojunctions, and support vasodilation. In marked contrast, SERCA2a may be entirely restricted to the deep, perinuclear SR and may supply calcium to this sub-compartment in support of vasoconstriction. RyR3 is also preferentially targeted to the perinuclear SR, where its clusters associate with lysosome-SR nanojunctions. The distribution of RyR2 is more widespread and extends from this region to the wider cell. Therefore, perinuclear RyR3s most likely support the initiation of global calcium waves at L-SR junctions, which subsequently propagate by calcium-induced calcium release via RyR2 in order to elicit contraction. Data also suggest that unique SERCA and RyR are preferentially targeted to invaginations of the nuclear membrane. Site- and function-specific calcium signals may thus arise to modulate stimulus-response coupling and transcriptional cascades.

Near-infrared light-controlled regulation of intracellular calcium to modulate macrophage polarization.

PubMed

Kang, Heemin; Zhang, Kunyu; Wong, Dexter Siu Hong; Han, Fengxuan; Li, Bin; Bian, Liming

2018-04-21

Macrophages are multifunctional immune cells with diverse physiological functions such as fighting against infection, influencing progression of pathologies, maintaining homeostasis, and regenerating tissues. Macrophages can be induced to adopt distinct polarized phenotypes, such as classically activated pro-inflammatory (M1) phenotypes or alternatively activated anti-inflammatory and pro-healing (M2), to execute diverse and dynamic immune functions. However, unbalanced polarizations of macrophage can lead to various pathologies, such as atherosclerosis, obesity, tumor, and asthma. Thus, the capability to remotely control macrophage phenotypes is important to the success of treating many pathological conditions involving macrophages. In this study, we developed an upconversion nanoparticle (UCNP)-based photoresponsive nanocarrier for near-infrared (NIR) light-mediated control of intracellular calcium levels to regulate macrophage polarization. UCNP was coated with mesoporous silica (UCNP@mSiO 2 ), into which loaded calcium regulators that can either supply or deplete calcium ions. UCNP@mSiO 2 was chemically modified through serial coupling of photocleavable linker and Arg-Gly-Asp (RGD) peptide-bearing molecular cap via cyclodextrin-adamantine host-guest complexation. The RGD-bearing cap functioned as the photolabile gating structure to control the release of calcium regulators and facilitated the cellular uptake of UCNP@mSiO 2 nanocarrier. The upconverted UV light emission from the UCNP@mSiO 2 under NIR light excitation triggered the cleavage of cap and intracellular release of calcium regulators, thereby allowing temporal regulation on the intracellular calcium levels. Application of NIR light through skin tissue promoted M1 or M2 polarization of macrophages, by elevating or depleting intracellular calcium levels, respectively. To the best of our knowledge, this is the first demonstration of NIR light-mediated remote control on macrophage polarization. This photoresponsive nanocarrier offers the potential to remotely manipulate in vivo immune functions, such as inflammation or tissue regeneration, via NIR light-controlled macrophage polarization. Copyright © 2018 Elsevier Ltd. All rights reserved.

Optimization of direct fibroblast reprogramming to cardiomyocytes using calcium activity as a functional measure of success.

PubMed

Addis, Russell C; Ifkovits, Jamie L; Pinto, Filipa; Kellam, Lori D; Esteso, Paul; Rentschler, Stacey; Christoforou, Nicolas; Epstein, Jonathan A; Gearhart, John D

2013-07-01

Direct conversion of fibroblasts to induced cardiomyocytes (iCMs) has great potential for regenerative medicine. Recent publications have reported significant progress, but the evaluation of reprogramming has relied upon non-functional measures such as flow cytometry for cardiomyocyte markers or GFP expression driven by a cardiomyocyte-specific promoter. The issue is one of practicality: the most stringent measures - electrophysiology to detect cell excitation and the presence of spontaneously contracting myocytes - are not readily quantifiable in the large numbers of cells screened in reprogramming experiments. However, excitation and contraction are linked by a third functional characteristic of cardiomyocytes: the rhythmic oscillation of intracellular calcium levels. We set out to optimize direct conversion of fibroblasts to iCMs with a quantifiable calcium reporter to rapidly assess functional transdifferentiation. We constructed a reporter system in which the calcium indicator GCaMP is driven by the cardiomyocyte-specific Troponin T promoter. Using calcium activity as our primary outcome measure, we compared several published combinations of transcription factors along with novel combinations in mouse embryonic fibroblasts. The most effective combination consisted of Hand2, Nkx2.5, Gata4, Mef2c, and Tbx5 (HNGMT). This combination is >50-fold more efficient than GMT alone and produces iCMs with cardiomyocyte marker expression, robust calcium oscillation, and spontaneous beating that persist for weeks following inactivation of reprogramming factors. HNGMT is also significantly more effective than previously published factor combinations for the transdifferentiation of adult mouse cardiac fibroblasts to iCMs. Quantification of calcium function is a convenient and effective means for the identification and evaluation of cardiomyocytes generated by direct reprogramming. Using this stringent outcome measure, we conclude that HNGMT produces iCMs more efficiently than previously published methods. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Calmodulin gene expression in response to mechanical wounding and Botrytis cinerea infection in tomato fruit

USDA-ARS?s Scientific Manuscript database

Calmodulin, a ubiquitous calcium sensor, plays an important role in decoding the stress-triggered intracellular calcium changes and regulates the functions of numerous target proteins involved in various physiological responses in plants. To determine the functional significance of calmodulin in fl...

Vitamin D-mediated calcium absorption in patients with clinically stable Crohn's disease: a pilot study

USDA-ARS?s Scientific Manuscript database

Vitamin D is the critical hormone for intestinal absorption of calcium. Optimal calcium absorption is important for proper mineralization of bone in the prevention of osteoporosis and osteoporotic fractures, among other important functions. Diseases associated with gut inflammation, such as Crohn's ...

Growth hormone secretagogues prevent dysregulation of skeletal muscle calcium homeostasis in a rat model of cisplatin‐induced cachexia

PubMed Central

Conte, Elena; Camerino, Giulia Maria; Mele, Antonietta; De Bellis, Michela; Pierno, Sabata; Rana, Francesco; Fonzino, Adriano; Caloiero, Roberta; Rizzi, Laura; Bresciani, Elena; Ben Haj Salah, Khoubaib; Fehrentz, Jean‐Alain; Martinez, Jean; Giustino, Arcangela; Mariggiò, Maria Addolorata; Coluccia, Mauro; Tricarico, Domenico; Lograno, Marcello Diego; De Luca, Annamaria; Torsello, Antonio; Conte, Diana

2017-01-01

Abstract Background Cachexia is a wasting condition associated with cancer types and, at the same time, is a serious and dose‐limiting side effect of cancer chemotherapy. Skeletal muscle loss is one of the main characteristics of cachexia that significantly contributes to the functional muscle impairment. Calcium‐dependent signaling pathways are believed to play an important role in skeletal muscle decline observed in cachexia, but whether intracellular calcium homeostasis is affected in this situation remains uncertain. Growth hormone secretagogues (GHS), a family of synthetic agonists of ghrelin receptor (GHS‐R1a), are being developed as a therapeutic option for cancer cachexia syndrome; however, the exact mechanism by which GHS interfere with skeletal muscle is not fully understood. Methods By a multidisciplinary approach ranging from cytofluorometry and electrophysiology to gene expression and histology, we characterized the calcium homeostasis in fast‐twitch extensor digitorum longus (EDL) muscle of adult rats with cisplatin‐induced cachexia and established the potential beneficial effects of two GHS (hexarelin and JMV2894) at this level. Additionally, in vivo measures of grip strength and of ultrasonography recordings allowed us to evaluate the functional impact of GHS therapeutic intervention. Results Cisplatin‐treated EDL muscle fibres were characterized by a ~18% significant reduction of the muscle weight and fibre diameter together with an up‐regulation of atrogin1/Murf‐1 genes and a down‐regulation of Pgc1‐a gene, all indexes of muscle atrophy, and by a two‐fold increase in resting intracellular calcium, [Ca2+]i, compared with control rats. Moreover, the amplitude of the calcium transient induced by caffeine or depolarizing high potassium solution as well as the store‐operated calcium entry were ~50% significantly reduced in cisplatin‐treated rats. Calcium homeostasis dysregulation parallels with changes of functional ex vivo (excitability and resting macroscopic conductance) and in vivo (forelimb force and muscle volume) outcomes in cachectic animals. Administration of hexarelin or JMV2894 markedly reduced the cisplatin‐induced alteration of calcium homeostasis by both common as well as drug‐specific mechanisms of action. This effect correlated with muscle function preservation as well as amelioration of various atrophic indexes, thus supporting the functional impact of GHS activity on calcium homeostasis. Conclusions Our findings provide a direct evidence that a dysregulation of calcium homeostasis plays a key role in cisplatin‐induced model of cachexia gaining insight into the etiopathogenesis of this form of muscle wasting. Furthermore, our demonstration that GHS administration efficaciously prevents cisplatin‐induced calcium homeostasis alteration contributes to elucidate the mechanism of action through which GHS could potentially ameliorate chemotherapy‐associated cachexia. PMID:28294567

Vitamin D, calcium, and cardiovascular mortality: a perspective from a plenary lecture given at the annual meeting of the American Association of Clinical Endocrinologists.

PubMed

Miller, Paul D

2011-01-01

To examine data showing associations between serum 25-hydroxyvitamin D levels and calcium intake and cardiovascular mortality. The articles reviewed include those published from 1992-2011 derived from search engines (PubMed, Scopus, Medscape) using the following search terms: vitamin D, calcium, cardiovascular events, cardiovascular mortality, all-cause mortality, vascular calcification, chronic kidney disease, renal stones, and hypercalciuria. Because these articles were not weighted (graded) on the level of evidence, this review reflects my own perspective on the data and how they should be applied to clinical management. For skeletal health, vitamin D and calcium are both needed to ensure proper skeletal growth (modeling) and repair (remodeling). Nutritional deficiencies of either vitamin D or calcium may lead to a spectrum of metabolic bone disorders. Excessive consumption of either nutrient has been linked to a variety of medical disorders, such as hypercalcemia or renal stones. There have also been associations between vitamin D or calcium intake and cardiovascular disease. However, neither of these associations have established evidence nor known causality for increasing cardiovascular risk or all-cause mortality in patients with creatinine clearances greater than 60 mL/min. In patients with more severe chronic kidney disease, stronger data link excess calcium (or phosphorus) intake and increase in vascular calcification, but not mortality. The safe upper limit for vitamin D intake is at least 4000 IU daily and probably 10 000 IU daily; for calcium, the safe upper limit is between 2000 and 3000 mg daily. While no solid scientific evidence validates that serum vitamin D levels between 15 and 70 ng/mL are associated with increased cardiovascular disease risk, stronger but inconsistent evidence shows an association between calcium supplementation greater than 500 mg daily and an increase in cardiovascular disease risk. Most professional societies suggest that replacement levels of these nutrients be personalized with the goal of reaching a 25-hydroxyvitamin D concentration between 30 and 50 ng/mL and a calcium intake of 1200 mg daily.

Effects of Iron Overload on Cardiac Calcium Regulation: Translational Insights Into Mechanisms and Management of a Global Epidemic.

PubMed

Khamseekaew, Juthamas; Kumfu, Sirinart; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2016-08-01

Iron overload cardiomyopathy occurs in a rare primary form (ie, hemochromatosis) and a very common secondary form in a host of hemoglobinopathies (eg, thalassemia, sickle cell anemia) of substantial and growing global prevalence, which have transformed iron overload cardiomyopathy into a worldwide epidemic. Intracellular calcium ([Ca(2+)]i) is known to be a critical regulator of myocardial function, in which it plays a key role in maintaining cardiac excitation-contraction coupling. It has been proposed that a disturbance in cardiac calcium regulation is a major contributor to left ventricular dysfunction in iron overload cardiomyopathy. This review comprehensively summarizes reports concerned with the effects of iron overload on cardiac calcium regulation, including alteration in the intracellular calcium level, voltage-gated calcium channel function, and calcium cycling protein activity. Consistent reports, as well as inconsistent findings, from both in vitro and in vivo studies, are presented and discussed. The understanding of these mechanisms has provided important new pathophysiological insights and has led to the development of novel therapeutic and preventive strategies for patients with iron overload cardiomyopathy that are currently in clinical trials. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Diagram of Calcium Movement in the Human Body

NASA Technical Reports Server (NTRS)

2002-01-01

This diagram shows the normal pathways of calcium movement in the body and indicates changes (green arrows) seen during preliminary space flight experiments. Calcium plays a central role because 1) it gives strength and structure to bone and 2) all types of cells require it to function normally. To better understand how and why weightlessness induces bone loss, astronauts have participated in a study of calcium kinetics -- that is, the movement of calcium through the body, including absorption from food, and its role in the formation and breakdown of bone.

Modeling CICR in rat ventricular myocytes: voltage clamp studies

PubMed Central

2010-01-01

Background The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR) in cardiac myocytes, with voltage clamp (VC) studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect Ca2+ loading of the sarcoplasmic reticulum (SR), and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR Ca2+ release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic Ca2+ concentration ([Ca2+]myo). Methods The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU), in which resides the mechanistic basis of CICR). The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed Ca2+ channels (trigger-channel and release-channel). It releases Ca2+ flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[Ca2+]myo. Results Our model reproduces measured VC data published by several laboratories, and generates graded Ca2+ release at high Ca2+ gain in a homeostatically-controlled environment where [Ca2+]myo is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR Ca2+ release, its activation by trigger Ca2+, and its refractory characteristics mediated by the luminal SR Ca2+ sensor. Proper functioning of the DCU, sodium-calcium exchangers and SERCA pump are important in achieving negative feedback control and hence Ca2+ homeostasis. Conclusions We examine the role of the above Ca2+ regulating mechanisms in handling various types of induced disturbances in Ca2+ levels by quantifying cellular Ca2+ balance. Our model provides biophysically-based explanations of phenomena associated with CICR generating useful and testable hypotheses. PMID:21062495

Calcium Orthophosphate-Containing Biocomposites and Hybrid Biomaterials for Biomedical Applications

PubMed Central

Dorozhkin, Sergey V.

2015-01-01

The state-of-the-art on calcium orthophosphate (CaPO4)-containing biocomposites and hybrid biomaterials suitable for biomedical applications is presented. Since these types of biomaterials offer many significant and exciting possibilities for hard tissue regeneration, this subject belongs to a rapidly expanding area of biomedical research. Through the successful combinations of the desired properties of matrix materials with those of fillers (in such systems, CaPO4 might play either role), innovative bone graft biomaterials can be designed. Various types of CaPO4-based biocomposites and hybrid biomaterials those are either already in use or being investigated for biomedical applications are extensively discussed. Many different formulations in terms of the material constituents, fabrication technologies, structural and bioactive properties, as well as both in vitro and in vivo characteristics have been already proposed. Among the others, the nano-structurally controlled biocomposites, those containing nanodimensional compounds, biomimetically fabricated formulations with collagen, chitin and/or gelatin, as well as various functionally graded structures seem to be the most promising candidates for clinical applications. The specific advantages of using CaPO4-based biocomposites and hybrid biomaterials in the selected applications are highlighted. As the way from a laboratory to a hospital is a long one and the prospective biomedical candidates have to meet many different necessities, the critical issues and scientific challenges that require further research and development are also examined. PMID:26262645

Better functional mobility in community-dwelling elderly is related to D-hormone serum levels and to daily calcium intake.

PubMed

Dukas, L; Staehelin, H B; Schacht, E; Bischoff, H A

2005-01-01

The influence of calcitropic hormones on functional mobility has been studied in vitamin D (calcidiol) deficient elderly or elderly with a history of falls, however, data in community-dwelling independent vitamin D replete elderly are missing. We therefore assessed in an observational survey the association of calcidiol (25(OH)D3) and calcitriol (D-hormone / 1,25(OH)2D3) status as well as of daily calcium intake on functional mobility in older subjects We evaluated 192 women and 188 men, aged superior 70 years and living independently. Average Timed-up and go test (TUG-test) in seconds was taken as measure of functional mobility. Calcidiol and D-hormone serum concentrations and daily calcium intake were studied in multivariate controlled linear regression models with TUG-test performance as the dependent variable and/or as dichotomous variables (deficient vs. non-deficient, above vs. below the median, respectively). Subjects with low D-hormone serum concentrations took significantly more time to perform the TUG-test (low = 7.70s +/- 2.52 SD ; high = 6.70s +/- 1.29 SD; p = 0.004). In the linear multivariate controlled regression model increased D-hormone serum concentrations predicted better TUG-test performance (estimate -0.0007, p = 0.044). Participants with a calcium intake of > or =512 mg/day were significantly faster to perform the TUG-test than participants with a daily calcium intake of <512 mg/day (estimate:-0.43, p = 0.007). Other significant predictors of better TUG-test performance in both models were: male gender, less comorbid conditions, younger age, lower BMI, iPTH serum levels and creatinine clearance. Calcidiol serum levels were not associated with TUG-test performance. Higher D-hormone status and a calcium intake of > or =512 mg/day in community-dwelling independent older persons are significant determinants of better functional mobility. Therefore, to ensure optimal functional mobility, the care of older persons should address correction of D-hormone deficiency and increasing daily calcium intake.

Reciprocal Interaction of Dendrite Geometry and Nuclear Calcium-VEGFD Signaling Gates Memory Consolidation and Extinction.

PubMed

Hemstedt, Thekla J; Bengtson, C Peter; Ramírez, Omar; Oliveira, Ana M M; Bading, Hilmar

2017-07-19

Nuclear calcium is an important signaling end point in synaptic excitation-transcription coupling that is critical for long-term neuroadaptations. Here, we show that nuclear calcium acting via a target gene, VEGFD, is required for hippocampus-dependent fear memory consolidation and extinction in mice. Nuclear calcium-VEGFD signaling upholds the structural integrity and complexity of the dendritic arbor of CA1 neurons that renders those cells permissive for the efficient generation of synaptic input-evoked nuclear calcium transients driving the expression of plasticity-related genes. Therefore, the gating of memory functions rests on the reciprocally reinforcing maintenance of an intact dendrite geometry and a functional synapse-to-nucleus communication axis. In psychiatric and neurodegenerative disorders, therapeutic application of VEGFD may help to stabilize dendritic structures and network connectivity, which may prevent cognitive decline and could boost the efficacy of extinction-based exposure therapies. SIGNIFICANCE STATEMENT This study uncovers a reciprocal relationship between dendrite geometry, the ability to generate nuclear calcium transients in response to synaptic inputs, and the subsequent induction of expression of plasticity-related and dendritic structure-preserving genes. Insufficient nuclear calcium signaling in CA1 hippocampal neurons and, consequently, reduced expression of the nuclear calcium target gene VEGFD, a dendrite maintenance factor, leads to reduced-complexity basal dendrites of CA1 neurons, which severely compromises the animals' consolidation of both memory and extinction memory. The structure-protective function of VEGFD may prove beneficial in psychiatric disorders as well as neurodegenerative and aging-related conditions that are associated with loss of neuronal structures, dysfunctional excitation-transcription coupling, and cognitive decline. Copyright © 2017 the authors 0270-6474/17/376946-10$15.00/0.

The use of flow cytometry to examine calcium signalling by TRPV1 in mixed cell populations.

PubMed

Assas, Bakri M; Abdulaal, Wesam H; Wakid, Majed H; Zakai, Haytham A; Miyan, J; Pennock, J L

2017-06-15

Flow cytometric analysis of calcium mobilisation has been in use for many years in the study of specific receptor engagement or isolated cell:cell communication. However, calcium mobilisation/signaling is key to many cell functions including apoptosis, mobility and immune responses. Here we combine multiplex surface staining of whole spleen with Indo-1 AM to visualise calcium mobilisation and examine calcium signaling in a mixed immune cell culture over time. We demonstrate responses to a TRPV1 agonist in distinct cell subtypes without the need for cell separation. Multi parameter staining alongside Indo-1 AM to demonstrate calcium mobilization allows the study of real time calcium signaling in a complex environment. Copyright © 2017. Published by Elsevier Inc.

The Regulatory Functions of Calcium and the Potential Role of Calcium in Mediating Gravitational Responses in Cells and Tissues

NASA Technical Reports Server (NTRS)

Roux, S. J. (Editor)

1983-01-01

The hypothesis that calcium plays an important part in regulating cellular response to gravity and to other environmental stimuli is explored. Topics covered include the role of calmodulin and other proteins, gravitropic responses, bone demineralization during space flight, and intracellular communication.

Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation

PubMed Central

Findeisen, Felix

2010-01-01

Voltage-gated calcium channels (CaVs) are large, transmembrane multiprotein complexes that couple membrane depolarization to cellular calcium entry. These channels are central to cardiac action potential propagation, neurotransmitter and hormone release, muscle contraction and calcium-dependent gene transcription. Over the past six years, the advent of high-resolution structural studies of CaV components from different isoforms and CaV modulators has begun to reveal the architecture that underlies the exceptionally rich feedback modulation that controls CaV action. These descriptions of CaV molecular anatomy have provided new, structure-based insights into the mechanisms by which particular channel elements affect voltage-dependent inactivation (VDI), calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF). The initial successes have been achieved through structural studies of soluble channel domains and modulator proteins and have proven most powerful when paired with biochemical and functional studies that validate ideas inspired by the structures. Here, we review the progress in this growing area and highlight some key open challenges for future efforts. PMID:21139419

Localization of the Calcium Regulated Citrate Transport Process in Proximal Tubule Cells

PubMed Central

Hering-Smith, Kathleen S.; Mao, Weibo; Schiro, Faith R.; Coleman-Barnett, Joycelynn; Pajor, Ana M.; Hamm, L. Lee

2014-01-01

Urinary citrate is an important inhibitor of calcium stone formation. Most of citrate reabsorption in the proximal tubule is thought to occur via a dicarboxylate transporter NaDC1 located in the apical membrane. OK cells, an established opossum kidney proximal tubule cell line, transport citrate but the characteristics change with extracellular calcium such that low calcium solutions stimulate total citrate transport as well as increase the apparent affinity for transport. The present studies address several fundamental properties of this novel process: the polarity of the transport process, the location of the calcium-sensitivity and whether NaDC1 is present in OK cells. OK cells grown on permeable supports exhibited apical > basolateral citrate transport. Apical transport of both citrate and succinate was sensitive to extracellular calcium whereas basolateral transport was not. Apical calcium, rather than basolateral, was the predominant determinant of changes in transport. Also 2,3-dimethylsuccinate, previously identified as an inhibitor of basolateral dicarboxylate transport, inhibited apical citrate uptake. Although the calcium-sensitive transport process in OK cells is functionally not typical NaDC1, NaDC1 is present in OK cells by Western blot and PCR. By immunolocalization studies, NaDC1 was predominantly located in discrete apical membrane or subapical areas. However by biotinylation, apical NaDC1 decreases in the apical membrane with lowering calcium. In sum, OK cells express a calcium-sensitive/regulated dicarboxylate process at the apical membrane which responds to variations in apical calcium. Despite the functional differences of this process compared to NaDC1, NaDC1 is present in these cells, but predominantly in subapical vesicles. PMID:24652587

Filamin and Phospholipase C-ε Are Required for Calcium Signaling in the Caenorhabditis elegans Spermatheca

PubMed Central

Kovacevic, Ismar; Orozco, Jose M.; Cram, Erin J.

2013-01-01

The Caenorhabditis elegans spermatheca is a myoepithelial tube that stores sperm and undergoes cycles of stretching and constriction as oocytes enter, are fertilized, and exit into the uterus. FLN-1/filamin, a stretch-sensitive structural and signaling scaffold, and PLC-1/phospholipase C-ε, an enzyme that generates the second messenger IP3, are required for embryos to exit normally after fertilization. Using GCaMP, a genetically encoded calcium indicator, we show that entry of an oocyte into the spermatheca initiates a distinctive series of IP3-dependent calcium oscillations that propagate across the tissue via gap junctions and lead to constriction of the spermatheca. PLC-1 is required for the calcium release mechanism triggered by oocyte entry, and FLN-1 is required for timely initiation of the calcium oscillations. INX-12, a gap junction subunit, coordinates propagation of the calcium transients across the spermatheca. Gain-of-function mutations in ITR-1/IP3R, an IP3-dependent calcium channel, and loss-of-function mutations in LFE-2, a negative regulator of IP3 signaling, increase calcium release and suppress the exit defect in filamin-deficient animals. We further demonstrate that a regulatory cassette consisting of MEL-11/myosin phosphatase and NMY-1/non-muscle myosin is required for coordinated contraction of the spermatheca. In summary, this study answers long-standing questions concerning calcium signaling dynamics in the C. elegans spermatheca and suggests FLN-1 is needed in response to oocyte entry to trigger calcium release and coordinated contraction of the spermathecal tissue. PMID:23671426

Trace element levels in drinking water and cognitive function among elderly Chinese.

PubMed

Emsley, C L; Gao, S; Li, Y; Liang, C; Ji, R; Hall, K S; Cao, J; Ma, F; Wu, Y; Ying, P; Zhang, Y; Sun, S; Unverzagt, F W; Slemenda, C W; Hendrie, H C

2000-05-01

The relation between trace element levels in drinking water and cognitive function was investigated in a population-based study of elderly residents (n = 1,016) in rural China in 1996-1997. Cognitive function was measured using a Chinese translation of the Community Screening Interview for Dementia. A mixed effects model was used to evaluate the effect of each of the elements on cognitive function while adjusting for age, sex, and educational level. Several of the elements examined had a significant effect on cognitive function when they were assessed in a univariate context. However, after adjustment for other elements, many of these results were not significant. There was a significant quadratic effect for calcium and a significant zinc-cadmium interaction. Cognitive function increased with calcium level up to a certain point and then decreased as calcium continued to increase. Zinc showed a positive relation with cognitive function at low cadmium levels but a negative relation at high levels.

The Hepatitis B Virus X Protein Elevates Cytosolic Calcium Signals by Modulating Mitochondrial Calcium Uptake

PubMed Central

Yang, Bei

2012-01-01

Chronic hepatitis B virus (HBV) infections are associated with the development of hepatocellular carcinoma (HCC). The HBV X protein (HBx) is thought to play an important role in the development of HBV-associated HCC. One fundamental HBx function is elevation of cytosolic calcium signals; this HBx activity has been linked to HBx stimulation of cell proliferation and transcription pathways, as well as HBV replication. Exactly how HBx elevates cytosolic calcium signals is not clear. The studies described here show that HBx stimulates calcium entry into cells, resulting in an increased plateau level of inositol 1,4,5-triphosphate (IP3)-linked calcium signals. This increased calcium plateau can be inhibited by blocking mitochondrial calcium uptake and store-operated calcium entry (SOCE). Blocking SOCE also reduced HBV replication. Finally, these studies also demonstrate that there is increased mitochondrial calcium uptake in HBx-expressing cells. Cumulatively, these studies suggest that HBx can increase mitochondrial calcium uptake and promote increased SOCE to sustain higher cytosolic calcium and stimulate HBV replication. PMID:22031934

The Role of Auxiliary Subunits for the Functional Diversity of Voltage-Gated Calcium Channels

PubMed Central

Campiglio, Marta; Flucher, Bernhard E

2015-01-01

Voltage-gated calcium channels (VGCCs) represent the sole mechanism to convert membrane depolarization into cellular functions like secretion, contraction, or gene regulation. VGCCs consist of a pore-forming α1 subunit and several auxiliary channel subunits. These subunits come in multiple isoforms and splice-variants giving rise to a stunning molecular diversity of possible subunit combinations. It is generally believed that specific auxiliary subunits differentially regulate the channels and thereby contribute to the great functional diversity of VGCCs. If auxiliary subunits can associate and dissociate from pre-existing channel complexes, this would allow dynamic regulation of channel properties. However, most auxiliary subunits modulate current properties very similarly, and proof that any cellular calcium channel function is indeed modulated by the physiological exchange of auxiliary subunits is still lacking. In this review we summarize available information supporting a differential modulation of calcium channel functions by exchange of auxiliary subunits, as well as experimental evidence in support of alternative functions of the auxiliary subunits. At the heart of the discussion is the concept that, in their native environment, VGCCs function in the context of macromolecular signaling complexes and that the auxiliary subunits help to orchestrate the diverse protein–protein interactions found in these calcium channel signalosomes. Thus, in addition to a putative differential modulation of current properties, differential subcellular targeting properties and differential protein–protein interactions of the auxiliary subunits may explain the need for their vast molecular diversity. J. Cell. Physiol. 999: 00–00, 2015. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. J. Cell. Physiol. 230: 2019–2031, 2015. © 2015 Wiley Periodicals, Inc. PMID:25820299

Tracking the Molecular Evolution of Calcium Permeability in a Nicotinic Acetylcholine Receptor

PubMed Central

Lipovsek, Marcela; Fierro, Angélica; Pérez, Edwin G.; Boffi, Juan C.; Millar, Neil S.; Fuchs, Paul A.; Katz, Eleonora; Elgoyhen, Ana Belén

2014-01-01

Nicotinic acetylcholine receptors are a family of ligand-gated nonselective cationic channels that participate in fundamental physiological processes at both the central and the peripheral nervous system. The extent of calcium entry through ligand-gated ion channels defines their distinct functions. The α9α10 nicotinic cholinergic receptor, expressed in cochlear hair cells, is a peculiar member of the family as it shows differences in the extent of calcium permeability across species. In particular, mammalian α9α10 receptors are among the ligand-gated ion channels which exhibit the highest calcium selectivity. This acquired differential property provides the unique opportunity of studying how protein function was shaped along evolutionary history, by tracking its evolutionary record and experimentally defining the amino acid changes involved. We have applied a molecular evolution approach of ancestral sequence reconstruction, together with molecular dynamics simulations and an evolutionary-based mutagenesis strategy, in order to trace the molecular events that yielded a high calcium permeable nicotinic α9α10 mammalian receptor. Only three specific amino acid substitutions in the α9 subunit were directly involved. These are located at the extracellular vestibule and at the exit of the channel pore and not at the transmembrane region 2 of the protein as previously thought. Moreover, we show that these three critical substitutions only increase calcium permeability in the context of the mammalian but not the avian receptor, stressing the relevance of overall protein structure on defining functional properties. These results highlight the importance of tracking evolutionarily acquired changes in protein sequence underlying fundamental functional properties of ligand-gated ion channels. PMID:25193338

Impaired mitochondria and intracellular calcium transients in the salivary glands of obese rats.

PubMed

Ittichaicharoen, Jitjiroj; Apaijai, Nattayaporn; Tanajak, Pongpan; Sa-Nguanmoo, Piangkwan; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2017-04-01

Long-term consumption of a high-fat diet (HFD) causes not only obese-insulin resistance, but is also associated with mitochondrial dysfunction in several organs. However, the effect of obese-insulin resistance on salivary glands has not been investigated. We hypothesized that obese-insulin resistance induced by HFD impaired salivary gland function by reducing salivation, increasing inflammation, and fibrosis, as well as impairing mitochondrial function and calcium transient signaling. Male Wistar rats (200-220 g) were fed either a ND or an HFD (n = 8/group) for 16 weeks. At the end of week 16, salivary flow rates, metabolic parameters, and plasma oxidative stress were determined. Rats were then sacrificed and submandibular glands were removed to determine inflammation, fibrosis, apoptosis, mitochondrial function and dynamics, and intracellular calcium transient signaling. Long-term consumption of an HFD caused obese-insulin resistance and increased oxidative stress, fibrosis, inflammation, and apoptosis in the salivary glands. In addition, impaired mitochondrial function, as indicated by increased mitochondrial reactive oxygen species, mitochondrial membrane depolarization, and mitochondrial swelling in salivary glands and impaired intracellular calcium regulation, as indicated by a reduced intracellular calcium transient rising rate, decay rates, and amplitude of salivary acinar cells, were observed in HFD-fed rats. However, salivary flow rate and level of aquaporin 5 protein were not different between both groups. Although HFD consumption did not affect salivation, it caused obese-insulin resistance, leading to pathophysiological alteration of salivary glands, including impaired intracellular calcium transients, increased oxidative stress and inflammation, and salivary mitochondrial dysfunction.

Structure and Function of Cardiac Troponin C (TNNC1): Implications for Heart Failure, Cardiomyopathies, and Troponin Modulating Drugs

PubMed Central

Li, Monica X.; Hwang, Peter M.

2015-01-01

In striated muscle, the protein troponin complex turns contraction on and off in a calcium-dependent manner. The calcium-sensing component of the complex is troponin C, which is expressed from the TNNC1 gene in both cardiac muscle and slow-twitch skeletal muscle (identical transcript in both tissues) and the TNNC2 gene in fast-twitch skeletal muscle. Cardiac troponin C (cTnC) is made up of two globular EF-hand domains connected by a flexible linker. The structural C-domain (cCTnC) contains two high affinity calcium-binding sites that are always occupied by Ca2+ or Mg2+ under physiologic conditions, stabilizing an open conformation that remains anchored to the rest of the troponin complex. In contrast, the regulatory N-domain (cNTnC) contains a single low affinity site that is largely unoccupied at resting calcium concentrations. During muscle activation, calcium binding to cNTnC favors an open conformation that binds to the switch region of troponin I, removing adjacent inhibitory regions of troponin I from actin and allowing muscle contraction to proceed. Regulation of the calcium binding affinity of cNTnC is physiologically important, because it directly impacts the calcium sensitivity of muscle contraction. Calcium sensitivity can be modified by drugs that stabilize the open form of cNTnC, post-translational modifications like phosphorylation of troponin I, or downstream thin filament protein interactions that impact the availability of the troponin I switch region. Recently, mutations in cTnC have been associated with hypertrophic or dilated cardiomyopathy. A detailed understanding of how calcium sensitivity is regulated through the troponin complex is necessary for explaining how mutations perturb its function to promote cardiomyopathy and how post-translational modifications in the thin filament affect heart function and heart failure. Troponin modulating drugs are being developed for the treatment of cardiomyopathies and heart failure. PMID:26232335

Gingerol activates noxious cold ion channel TRPA1 in gastrointestinal tract.

PubMed

Yang, Meng-Qi; Ye, Lin-Lan; Liu, Xiao-Ling; Qi, Xiao-Ming; Lv, Jia-Di; Wang, Gang; Farhan, Ulah-Khan; Waqas, Nawaz; Chen, Ding-Ding; Han, Lei; Zhou, Xiao-Hui

2016-06-01

TRPA1 channels are non-selective cation channels that could be activated by plant-derived pungent products, including gingerol, a main active constituent of ginger. Ginger could improve the digestive function; however whether ginger improves the digestive function through activating TRPA1 receptor in gastrointestinal tract has not been investigated. In the present study, gingerol was used to stimulate cell lines (RIN14B or STC-1) while depletion of extracellular calcium. TRPA1 inhibitor (rethenium red) and TRPA1 gene silencing via TRPA1-specific siRNA were also used for mechanistic studies. The intracellular calcium and secretion of serotonin or cholecystokinin were measured by fura-2/AM and ELISA. Stimulation of those cells with gingerol increased intracellular calcium levels and the serotonin or cholecystokinin secretion. The gingerol-induced intracellular calcium increase and secretion (serotonin or cholecystokinin) release were completely blocked by ruthenium red, EGTA, and TRPA1-specific siRNA. In summary, our results suggested that gingerol derived from ginger might improve the digestive function through secretion releasing from endocrine cells of the gut by inducing TRPA1-mediated calcium influx. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Calcium Nutrition and Extracellular Calcium Sensing: Relevance for the Pathogenesis of Osteoporosis, Cancer and Cardiovascular Diseases

PubMed Central

Peterlik, Meinrad; Kállay, Enikoe; Cross, Heide S.

2013-01-01

Through a systematic search in Pubmed for literature, on links between calcium malnutrition and risk of chronic diseases, we found the highest degree of evidence for osteoporosis, colorectal and breast cancer, as well as for hypertension, as the only major cardiovascular risk factor. Low calcium intake apparently has some impact also on cardiovascular events and disease outcome. Calcium malnutrition can causally be related to low activity of the extracellular calcium-sensing receptor (CaSR). This member of the family of 7-TM G-protein coupled receptors allows extracellular Ca2+ to function as a “first messenger” for various intracellular signaling cascades. Evidence demonstrates that Ca2+/CaSR signaling in functional linkage with vitamin D receptor (VDR)-activated pathways (i) promotes osteoblast differentiation and formation of mineralized bone; (ii) targets downstream effectors of the canonical and non-canonical Wnt pathway to inhibit proliferation and induce differentiation of colorectal cancer cells; (iii) evokes Ca2+ influx into breast cancer cells, thereby activating pro-apoptotic intracellular signaling. Furthermore, Ca2+/CaSR signaling opens Ca2+-sensitive K+ conductance channels in vascular endothelial cells, and also participates in IP3-dependent regulation of cytoplasmic Ca2+, the key intermediate of cardiomyocyte functions. Consequently, impairment of Ca2+/CaSR signaling may contribute to inadequate bone formation, tumor progression, hypertension, vascular calcification and, probably, cardiovascular disease. PMID:23340319

Impaired Calcium Entry into Cells Is Associated with Pathological Signs of Zinc Deficiency12

PubMed Central

O’Dell, Boyd L.; Browning, Jimmy D.

2013-01-01

Zinc is an essential trace element whose deficiency gives rise to specific pathological signs. These signs occur because an essential metabolic function is impaired as the result of failure to form or maintain a specific metal-ion protein complex. Although zinc is a component of many essential metalloenzymes and transcription factors, few of these have been identified with a specific sign of incipient zinc deficiency. Zinc also functions as a structural component of other essential proteins. Recent research with Swiss murine fibroblasts, 3T3 cells, has shown that zinc deficiency impairs calcium entry into cells, a process essential for many cell functions, including proliferation, maturation, contraction, and immunity. Impairment of calcium entry and the subsequent failure of cell proliferation could explain the growth failure associated with zinc deficiency. Defective calcium uptake is associated with impaired nerve transmission and pathology of the peripheral nervous system, as well as the failure of platelet aggregation and the bleeding tendency of zinc deficiency. There is a strong analogy between the pathology of genetic diseases that result in impaired calcium entry and other signs of zinc deficiency, such as decreased and cyclic food intake, taste abnormalities, abnormal water balance, skin lesions, impaired reproduction, depressed immunity, and teratogenesis. This analogy suggests that failure of calcium entry is involved in these signs of zinc deficiency as well. PMID:23674794

Calcium metabolism in health and disease.

PubMed

Peacock, Munro

2010-01-01

This brief review focuses on calcium balance and homeostasis and their relationship to dietary calcium intake and calcium supplementation in healthy subjects and patients with chronic kidney disease and mineral bone disorders (CKD-MBD). Calcium balance refers to the state of the calcium body stores, primarily in bone, which are largely a function of dietary intake, intestinal absorption, renal excretion, and bone remodeling. Bone calcium balance can be positive, neutral, or negative, depending on a number of factors, including growth, aging, and acquired or inherited disorders. Calcium homeostasis refers to the hormonal regulation of serum ionized calcium by parathyroid hormone, 1,25-dihydroxyvitamin D, and serum ionized calcium itself, which together regulate calcium transport at the gut, kidney, and bone. Hypercalcemia and hypocalcemia indicate serious disruption of calcium homeostasis but do not reflect calcium balance on their own. Calcium balance studies have determined the dietary and supplemental calcium requirements needed to optimize bone mass in healthy subjects. However, similar studies are needed in CKD-MBD, which disrupts both calcium balance and homeostasis, because these data in healthy subjects may not be generalizable to this patient group. Importantly, increasing evidence suggests that calcium supplementation may enhance soft tissue calcification and cardiovascular disease in CKD-MBD. Further research is needed to elucidate the risks and mechanisms of soft tissue calcification with calcium supplementation in both healthy subjects and CKD-MBD patients.

Functional and Structural Analysis of the Conserved EFhd2 Protein

PubMed Central

Acosta, Yancy Ferrer; Rodríguez Cruz, Eva N.; Vaquer, Ana del C.; Vega, Irving E.

2013-01-01

EFhd2 is a novel protein conserved from C. elegans to H. sapiens. This novel protein was originally identified in cells of the immune and central nervous systems. However, it is most abundant in the central nervous system, where it has been found associated with pathological forms of the microtubule-associated protein tau. The physiological or pathological roles of EFhd2 are poorly understood. In this study, a functional and structural analysis was carried to characterize the molecular requirements for EFhd2’s calcium binding activity. The results showed that mutations of a conserved aspartate on either EF-hand motif disrupted the calcium binding activity, indicating that these motifs work in pair as a functional calcium binding domain. Furthermore, characterization of an identified single-nucleotide polymorphisms (SNP) that introduced a missense mutation indicates the importance of a conserved phenylalanine on EFhd2 calcium binding activity. Structural analysis revealed that EFhd2 is predominantly composed of alpha helix and random coil structures and that this novel protein is thermostable. EFhd2’s thermo stability depends on its N-terminus. In the absence of the N-terminus, calcium binding restored EFhd2’s thermal stability. Overall, these studies contribute to our understanding on EFhd2 functional and structural properties, and introduce it into the family of canonical EF-hand domain containing proteins. PMID:22973849

TMEM203 Is a Novel Regulator of Intracellular Calcium Homeostasis and Is Required for Spermatogenesis

PubMed Central

Shambharkar, Prashant B.; Bittinger, Mark; Latario, Brian; Xiong, ZhaoHui; Bandyopadhyay, Somnath; Davis, Vanessa; Lin, Victor; Yang, Yi; Valdez, Reginald; Labow, Mark A.

2015-01-01

Intracellular calcium signaling is critical for initiating and sustaining diverse cellular functions including transcription, synaptic signaling, muscle contraction, apoptosis and fertilization. Trans-membrane 203 (TMEM203) was identified here in cDNA overexpression screens for proteins capable of modulating intracellular calcium levels using activation of a calcium/calcineurin regulated transcription factor as an indicator. Overexpression of TMEM203 resulted in a reduction of Endoplasmic Reticulum (ER) calcium stores and elevation in basal cytoplasmic calcium levels. TMEM203 protein was localized to the ER and found associated with a number of ER proteins which regulate ER calcium entry and efflux. Mouse Embryonic Fibroblasts (MEFs) derived from Tmem203 deficient mice had reduced ER calcium stores and altered calcium homeostasis. Tmem203 deficient mice were viable though male knockout mice were infertile and exhibited a severe block in spermiogenesis and spermiation. Expression profiling studies showed significant alternations in expression of calcium channels and pumps in testes and concurrently Tmem203 deficient spermatocytes demonstrated significantly altered calcium handling. Thus Tmem203 is an evolutionarily conserved regulator of cellular calcium homeostasis, is required for spermatogenesis and provides a causal link between intracellular calcium regulation and spermiogenesis. PMID:25996873

Excessive dietary calcium in the disruption of structural and functional status of adult male reproductive system in rat with possible mechanism.

PubMed

K Chandra, Amar; Sengupta, Pallav; Goswami, Haimanti; Sarkar, Mahitosh

2012-05-01

Calcium is essential for functioning of different systems including male reproduction. However, it has also been reported as chemo-castrative agent. The study has been undertaken to elucidate the effect of excessive dietary calcium on male reproductive system in animals with possible action. Adult male healthy rats fed CaCl(2) at different doses (0.5, 1.0 and 1.5 g%) in diet for 13 and 26 days to investigate reproductive parameters as well as the markers of oxidative stress. Significant alteration was found (P < 0.05) in testicular and accessory sex organs weight, epididymal sperm count, testicular steroidogenic enzyme (Δ(5) 3β-HSD and 17β-HSD) activities, serum testosterone, LH, FSH, LPO, activities of antioxidant enzymes, testicular histoarchitecture along with adrenal Δ(5) 3β-HSD activity with corticosterone level in dose- and time-dependent manner. Overall observations suggest that excessive dietary calcium enhances the generation of free-radicals resulting in structural and functional disruption of male reproduction.

Functional and molecular features of the calmodulin-interacting protein IQCG required for haematopoiesis in zebrafish.

PubMed

Chen, Li-Ting; Liang, Wen-Xue; Chen, Shuo; Li, Ren-Ke; Tan, Jue-Ling; Xu, Peng-Fei; Luo, Liu-Fei; Wang, Lei; Yu, Shan-He; Meng, Guoyu; Li, Keqin Kathy; Liu, Ting-Xi; Chen, Zhu; Chen, Sai-Juan

2014-05-02

We previously reported a fusion protein NUP98-IQCG in an acute leukaemia, which functions as an aberrant regulator of transcriptional expression, yet the structure and function of IQCG have not been characterized. Here we use zebrafish to investigate the role of iqcg in haematopoietic development, and find that the numbers of haematopoietic stem cells and multilineage-differentiated cells are reduced in iqcg-deficient embryos. Mechanistically, IQCG binds to calmodulin (CaM) and acts as a molecule upstream of CaM-dependent kinase IV (CaMKIV). Crystal structures of complexes between CaM and IQ domain of IQCG reveal dual CaM-binding footprints in this motif, and provide a structural basis for a higher CaM-IQCG affinity when deprived of calcium. The results collectively allow us to understand IQCG-mediated calcium signalling in haematopoiesis, and propose a model in which IQCG stores CaM at low cytoplasmic calcium concentrations, and releases CaM to activate CaMKIV when calcium level rises.

Physico-functional and mechanical properties of chitosan and calcium salts incorporated fish gelatin scaffolds.

PubMed

Jeevithan, E; Jeya Shakila, R; Varatharajakumar, A; Jeyasekaran, G; Sukumar, D

2013-09-01

Four types of fish gelatin scaffolds viz. gelatin (G), gelatin-chitosan (GC), gelatin-calcium acetate (GCA) and gelatin-chitosan-calcium acetate (GCCA) prepared were investigated for their functional properties, biomechanical strength, microstructural changes in relation to biodegradation. GC scaffold was superior with pH 3.15 and viscosity 9.40 cP. Chitosan and calcium acetate improved tensile strength (TS) and Young's modulus (YM), but lowered elongation at break (EAB). GCCA scaffold possessed moderate TS of 19.6 MPa, EAB of 4.76% and YM of 185 MPa. Foaming ability ratio of GC scaffold was high (3.41). GCA and GCCA scaffolds remained for 4 days before complete in vitro biodegradation. GC scaffold had larger cavities (180-300 μm) that were responsible for low swelling ratios and shrinkage factor. GCCA scaffold with moderate swelling rates, mechanical, functional properties and lowered biodegradation rate were found more suitable for biomedical applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Treatment of pressure sores in spina bifida patients with calcium alginate and foam dressings.

PubMed

Ausili, E; Paolucci, V; Triarico, S; Maestrini, C; Murolo, D; Focarelli, B; Rendeli, C

2013-06-01

Prospective study on local treatment of pressure sores using calcium alginate and foam dressings in spina bifida patients. Investigate if this sequential approach is valid and safe for selected patients with neurological impairments. Using European Pressure Ulcer Grading System, after clinical evaluation of local sore, selected patients of Spina Bifida Center of Rome were treated with sequential calcium alginate and foam dressings for 12 weeks. Pressure ulcere surfaces were measured monthly by ulcer tracing. The endpoints were the mean absolute areas surface reduction during every month and number of patients achieving a 50% or more during study. 14 patients (7 males aged 12-24 years) with spina bifida and pressure sores were treated. Mean and standard deviation of mean surface area reduction were 12.5 ± 7.5 cm 2 at start of the study versus 3.7 ± 5.2 cm 2 after 12 weeks, p < 0.001. 75% of the patients reached mean surface area reduction of 50% during trial. Dressing tolerance was good in every patient. Calcium alginate and foam dressings are valid and safe approach in the treatment of pressure sores in selected patients with spina bifida. In fact, they protect the wound and create an environment favorable to healing.

Genetically Encoded Calcium Indicators For Studying Long-Term Calcium Dynamics During Apoptosis

PubMed Central

Garcia, M. Iveth; Chen, Jessica J.; Boehning, Darren

2017-01-01

Intracellular calcium release is essential for regulating almost all cellular functions. Specific spatio-temporal patterns of cytosolic calcium elevations are critical determinants of cell fate in response to pro-apoptotic cellular stressors. As the apoptotic program can take hours or days, measurement of long-term calcium dynamics are essential for understanding the mechanistic role of calcium in apoptotic cell death. Due to the technical limitations of using calcium-sensitive dyes to measure cytosolic calcium little is known about long-term calcium dynamics in living cells after treatment with apoptosis-inducing drugs. Genetically encoded calcium indicators could potentially overcome some of the limitations of calcium-sensitive dyes. Here, we compared the performance of the genetically encoded calcium indicators GCaMP6s and GCaMP6f with the ratiometric dye Fura-2. GCaMP6s performed as well or better than Fura-2 in detecting agonist-induced calcium transients. We then examined the utility of GCaMP6s for continuously measuring apoptotic calcium release over the course of ten hours after treatment with staurosporine. We found that GCaMP6s was suitable for measuring apoptotic calcium release over long time courses and revealed significant heterogeneity in calcium release dynamics in individual cells challenged with staurosporine. Our results suggest GCaMP6s is an excellent indicator for monitoring long-term changes cytosolic calcium during apoptosis. PMID:28073595

[Ca2+]i oscillations in ASM: relationship with persistent airflow obstruction in asthma.

PubMed

Sweeney, David; Hollins, Fay; Gomez, Edith; Saunders, Ruth; Challiss, R A John; Brightling, Christopher E

2014-07-01

The cause of airway smooth muscle (ASM) hypercontractility in asthma is not fully understood. The relationship of spontaneous intracellular calcium oscillation frequency in ASM to asthma severity was investigated. Oscillations were increased in subjects with impaired lung function abolished by extracellular calcium removal, attenuated by caffeine and unaffected by verapamil or nitrendipine. Whether modulation of increased spontaneous intracellular calcium oscillations in ASM from patients with impaired lung function represents a therapeutic target warrants further investigation. © 2014 The Authors. Respirology published by Wiley Publishing Asia Pty Ltd on behalf of Asian Pacific Society of Respirology.

Increasing weight-bearing physical activity and calcium-rich foods to promote bone mass gains among 9–11 year old girls: outcomes of the Cal-Girls study

PubMed Central

French, Simone A; Story, Mary; Fulkerson, Jayne A; Himes, John H; Hannan, Peter; Neumark-Sztainer, Dianne; Ensrud, Kristine

2005-01-01

Background A two-year, community-based, group-randomized trial to promote bone mass gains among 9–11 year-old girls through increased intake of calcium-rich foods and weight-bearing physical activity was evaluated. Methods Following baseline data collection, 30 5th-grade Girl Scout troops were randomized to a two-year behavioral intervention program or to a no-treatment control group. Evaluations were conducted at baseline, one year, and two years. Measures included bone mineral content, density, and area (measured by DXA), dietary calcium intake (24-hour recall), and weight-bearing physical activity (physical activity checklist interview). Mixed-model regression was used to evaluate treatment-related changes in bone mineral content (g) for the total body, lumbar spine (L1-L4), proximal femur, one-third distal radius, and femoral neck. Changes in eating and physical activity behavioral outcomes were examined. Results Although the intervention was implemented with high fidelity, no significant intervention effects were observed for total bone mineral content or any specific bone sites. Significant intervention effects were observed for increases in dietary calcium. No significant intervention effects were observed for increases in weight-bearing physical activity. Conclusion Future research needs to identify the optimal dosage of weight-bearing physical activity and calcium-rich dietary behavior change required to maximize bone mass gains in pre-adolescent and adolescent girls. PMID:16029507

xCT expression reduces the early cell cycle requirement for calcium signaling

PubMed Central

Lastro, Michele; Kourtidis, Antonis; Farley, Kate; Conklin, Douglas S.

2009-01-01

Calcium has long been recognized as an important regulator of cell cycle transitions although the mechanisms are largely unknown. A functional genomic screen has identified genes involved in the regulation of early cell cycle progression by calcium. These genes when overexpressed confer the ability to bypass the G1/S arrest induced by Ca2+- channel antagonists in mouse fibroblasts. Overexpression of the cystine-glutamate exchanger, xCT, had the greatest ability to evade calcium antagonist-induced cell cycle arrest. xCT carries out the rate limiting step of glutathione synthesis in many cell types and is responsible for the uptake of cystine in most human cancer cell lines. Functional analysis indicates that the cystine uptake activity of xCT overcomes the G1/S arrest induced by Ca2+- channel antagonists by bypassing the requirement for calcium signaling. Since cells overexpressing xCT were found to have increased levels and activity of the AP-1 transcription factor in G1, redox stimulation of AP-1 activity accounts for the observed growth of these cells in the presence of calcium channel antagonists. These results suggest that reduced calcium signaling impairs AP-1 activation and that xCT expression may directly affect cell proliferation. PMID:18054200

Putting out the fire: what terminates calcium-induced calcium release in cardiac muscle?

PubMed

Stern, Michael D; Cheng, Heping

2004-06-01

The majority of contractile calcium in cardiac muscle is released from stores in the sarcoplasmic reticulum (SR), by a process of calcium-induced calcium release (CICR) through ryanodine receptors. Because CICR is intrinsically self-reinforcing, the stability of and graded regulation of cardiac EC coupling appear paradoxical. It is now well established that this gradation results from the stochastic recruitment of varying numbers of elementary local release events, which may themselves be regenerative, and which can be directly observed as calcium sparks. Ryanodine receptors (RyRs) are clustered in dense lattices, and most calcium sparks are now believed to involve activation of multiple RyRs. This implies that local CICR is regenerative, requiring a mechanism to terminate it. It was initially assumed that this mechanism was inactivation of the RyR, but during the decade since the discovery of sparks, no sufficiently strong inactivation mechanism has been demonstrated in vitro and all empirically determined gating schemes for the RyR give unstable EC coupling in Monte Carlo simulations. We consider here possible release termination mechanisms. Stochastic attrition is the spontaneous decay of active clusters due to random channel closure; calculations show that it is much too slow unless assisted by another process. Calcium-dependent RyR inactivation involving third-party proteins remains a viable but speculative mechanism; current candidates include calmodulin and sorcin. Local depletion of SR release terminal calcium could terminate release, however calculations and measurements leave it uncertain whether a sufficient diffusion resistance exists within the SR to sustain such depletion. Depletion could be assisted by dependence of RyR activity on SR lumenal [Ca(2+)]. There is substantial evidence for such lumenal activation, but it is not clear if it is a strong enough effect to account for the robust termination of sparks. The existence of direct interactions among clustered RyRs might account for the discrepancy between the inactivation properties of isolated RyRs and intact clusters. Such coupled gating remains controversial. Determining the mechanism of release termination is the outstanding unsolved problem of cardiac EC coupling, and will probably require extensive genetic manipulation of the EC coupling apparatus in its native environment to unravel the solution.

Cardiac Calcifications on Echocardiography Are Associated with Mortality and Stroke.

PubMed

Lu, Marvin Louis Roy; Gupta, Shuchita; Romero-Corral, Abel; Matejková, Magdaléna; De Venecia, Toni; Obasare, Edinrin; Bhalla, Vikas; Pressman, Gregg S

2016-12-01

Calcium deposits in the aortic valve and mitral annulus have been associated with cardiovascular events and mortality. However, there is no accepted standard method for scoring such cardiac calcifications, and most existing methods are simplistic. The aim of this study was to test the hypothesis that a semiquantitative score, one that accounts for all visible calcium on echocardiography, could predict all-cause mortality and stroke in a graded fashion. This was a retrospective study of 443 unselected subjects derived from a general echocardiography database. A global cardiac calcium score (GCCS) was applied that assigned points for calcification in the aortic root and valve, mitral annulus and valve, and submitral apparatus, and points for restricted leaflet mobility. The primary outcome was all-cause mortality, and the secondary outcome was stroke. Over a mean 3.8 ± 1.7 years of follow-up, there were 116 deaths and 34 strokes. Crude mortality increased in a graded fashion with increasing GCCS. In unadjusted proportional hazard analysis, the GCCS was significantly associated with total mortality (hazard ratio, 1.26; 95% CI, 1.17-1.35; P < .0001) and stroke (hazard ratio, 1.23; 95% CI, 1.07-1.40; P = .003). After adjusting for demographic and clinical factors (age, gender, body mass index, diabetes, hypertension, dyslipidemia, smoking, family history of coronary disease, chronic kidney disease, history of atrial fibrillation, and history of stroke), these associations remained significant. The GCCS is easily applied to routinely acquired echocardiograms and has clinically significant associations with total mortality and stroke. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Intracellular sphingosine releases calcium from lysosomes.

PubMed

Höglinger, Doris; Haberkant, Per; Aguilera-Romero, Auxiliadora; Riezman, Howard; Porter, Forbes D; Platt, Frances M; Galione, Antony; Schultz, Carsten

2015-11-27

To elucidate new functions of sphingosine (Sph), we demonstrate that the spontaneous elevation of intracellular Sph levels via caged Sph leads to a significant and transient calcium release from acidic stores that is independent of sphingosine 1-phosphate, extracellular and ER calcium levels. This photo-induced Sph-driven calcium release requires the two-pore channel 1 (TPC1) residing on endosomes and lysosomes. Further, uncaging of Sph leads to the translocation of the autophagy-relevant transcription factor EB (TFEB) to the nucleus specifically after lysosomal calcium release. We confirm that Sph accumulates in late endosomes and lysosomes of cells derived from Niemann-Pick disease type C (NPC) patients and demonstrate a greatly reduced calcium release upon Sph uncaging. We conclude that sphingosine is a positive regulator of calcium release from acidic stores and that understanding the interplay between Sph homeostasis, calcium signaling and autophagy will be crucial in developing new therapies for lipid storage disorders such as NPC.

Biotechnology

NASA Image and Video Library

2002-07-31

This diagram shows the normal pathways of calcium movement in the body and indicates changes (green arrows) seen during preliminary space flight experiments. Calcium plays a central role because 1) it gives strength and structure to bone and 2) all types of cells require it to function normally. To better understand how and why weightlessness induces bone loss, astronauts have participated in a study of calcium kinetics -- that is, the movement of calcium through the body, including absorption from food, and its role in the formation and breakdown of bone.

Mutations Affecting G-Protein Subunit α11 in Hypercalcemia and Hypocalcemia

PubMed Central

Babinsky, Valerie N.; Head, Rosie A.; Cranston, Treena; Rust, Nigel; Hobbs, Maurine R.; Heath, Hunter; Thakker, Rajesh V.

2013-01-01

BACKGROUND Familial hypocalciuric hypercalcemia is a genetically heterogeneous disorder with three variants: types 1, 2, and 3. Type 1 is due to loss-of-function mutations of the calcium-sensing receptor, a guanine nucleotide–binding protein (G-protein)–coupled receptor that signals through the G-protein subunit α11 (Gα11). Type 3 is associated with adaptor-related protein complex 2, sigma 1 subunit (AP2S1) mutations, which result in altered calcium-sensing receptor endocytosis. We hypothesized that type 2 is due to mutations effecting Gα11 loss of function, since Gα11 is involved in calcium-sensing receptor signaling, and its gene (GNA11) and the type 2 locus are colocalized on chromosome 19p13.3. We also postulated that mutations effecting Gα11 gain of function, like the mutations effecting calcium-sensing receptor gain of function that cause autosomal dominant hypocalcemia type 1, may lead to hypocalcemia. METHODS We performed GNA11 mutational analysis in a kindred with familial hypocalciuric hypercalcemia type 2 and in nine unrelated patients with familial hypocalciuric hypercalcemia who did not have mutations in the gene encoding the calcium-sensing receptor (CASR) or AP2S1. We also performed this analysis in eight unrelated patients with hypocalcemia who did not have CASR mutations. In addition, we studied the effects of GNA11 mutations on Gα11 protein structure and calcium-sensing receptor signaling in human embryonic kidney 293 (HEK293) cells. RESULTS The kindred with familial hypocalciuric hypercalcemia type 2 had an in-frame deletion of a conserved Gα11 isoleucine (Ile200del), and one of the nine unrelated patients with familial hypocalciuric hypercalcemia had a missense GNA11 mutation (Leu135Gln). Missense GNA11 mutations (Arg181Gln and Phe341Leu) were detected in two unrelated patients with hypocalcemia; they were therefore identified as having autosomal dominant hypocalcemia type 2. All four GNA11 mutations predicted disrupted protein structures, and assessment on the basis of in vitro expression showed that familial hypocalciuric hypercalcemia type 2–associated mutations decreased the sensitivity of cells expressing calcium-sensing receptors to changes in extracellular calcium concentrations, whereas autosomal dominant hypocalcemia type 2–associated mutations increased cell sensitivity. CONCLUSIONS Gα11 mutants with loss of function cause familial hypocalciuric hypercalcemia type 2, and Gα11 mutants with gain of function cause a clinical disorder designated as autosomal dominant hypocalcemia type 2. (Funded by the United Kingdom Medical Research Council and others.) PMID:23802516

Distribution of L-type calcium channels in rat thalamic neurones.

PubMed

Budde, T; Munsch, T; Pape, H C

1998-02-01

One major pathway for calcium entry into neurones is through voltage-activated calcium channels. The distribution of calcium channels over the membrane surface is important for their contribution to neuronal function. Electrophysiological recordings from thalamic cells in situ and after acute isolation demonstrated the presence of high-voltage activated calcium currents. The use of specific L-type calcium channel agonists and antagonists of the dihydropyridine type revealed an about 40% contribution of L-type channels to the total high-voltage-activated calcium current. In order to localize L-type calcium channels in thalamic neurones, fluorescent dihydropyridines were used. They were combined with the fluorescent dye RH414, which allowed the use of a ratio technique and thereby the determination of channel density. The distribution of L-type channels was analysed in the three main thalamic cell types: thalamocortical relay cells, local interneurones and reticular thalamic neurones. While channel density was highest in the soma and decreased significantly in the dendritic region, channels appeared to be clustered differentially in the three types of cells. In thalamocortical cells, L-type channels were clustered in high density around the base of dendrites, while they were more evenly distributed on the soma of interneurones. Reticular thalamic neurones exhibited high density of L-type channels in more central somatic regions. The differential localization of L-type calcium channels found in this study implies their predominate involvement in the regulation of somatic and proximal dendritic calcium-dependent processes, which may be of importance for specific thalamic functions, such as those mediating the transition from rhythmic burst activity during sleep to single spike activity during wakefulness or regulating the relay of visual information.

Iron Mediates N-Methyl-d-aspartate Receptor-dependent Stimulation of Calcium-induced Pathways and Hippocampal Synaptic Plasticity*

PubMed Central

Muñoz, Pablo; Humeres, Alexis; Elgueta, Claudio; Kirkwood, Alfredo; Hidalgo, Cecilia; Núñez, Marco T.

2011-01-01

Iron deficiency hinders hippocampus-dependent learning processes and impairs cognitive performance, but current knowledge on the molecular mechanisms underlying the unique role of iron in neuronal function is sparse. Here, we investigated the participation of iron on calcium signal generation and ERK1/2 stimulation induced by the glutamate agonist N-methyl-d-aspartate (NMDA), and the effects of iron addition/chelation on hippocampal basal synaptic transmission and long-term potentiation (LTP). Addition of NMDA to primary hippocampal cultures elicited persistent calcium signals that required functional NMDA receptors and were independent of calcium influx through L-type calcium channels or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors; NMDA also promoted ERK1/2 phosphorylation and nuclear translocation. Iron chelation with desferrioxamine or inhibition of ryanodine receptor (RyR)-mediated calcium release with ryanodine-reduced calcium signal duration and prevented NMDA-induced ERK1/2 activation. Iron addition to hippocampal neurons readily increased the intracellular labile iron pool and stimulated reactive oxygen species production; the antioxidant N-acetylcysteine or the hydroxyl radical trapper MCI-186 prevented these responses. Iron addition to primary hippocampal cultures kept in calcium-free medium elicited calcium signals and stimulated ERK1/2 phosphorylation; RyR inhibition abolished these effects. Iron chelation decreased basal synaptic transmission in hippocampal slices, inhibited iron-induced synaptic stimulation, and impaired sustained LTP in hippocampal CA1 neurons induced by strong stimulation. In contrast, iron addition facilitated sustained LTP induction after suboptimal tetanic stimulation. Together, these results suggest that hippocampal neurons require iron to generate RyR-mediated calcium signals after NMDA receptor stimulation, which in turn promotes ERK1/2 activation, an essential step of sustained LTP. PMID:21296883

Calcium sources for milk production in Holstein cows via changes in dry matter intake, mineral utilization, and mineral source buffering potential.

PubMed

Wohlt, J E; Ritter, D E; Evans, J L

1986-11-01

Three supplemental sources of inorganic calcium (calcite flour, aragonite, albacar), each differing in particle size and rate of reactivity, provided .6 or .9% calcium in corn silage:grain (1:1 dry matter) diets of high producing dairy cows. All cows were fed calcite flour at .6% calcium during the first 4 wk of lactation. On d 29 of lactation 5 cows were assigned to each of the six diets. Peak milk yield paralleled dry matter intake and was higher when calcite flour and aragonite provided .9% calcium, intermediate when all sources provided .6% calcium, and lower when albacar provided .9% calcium. However, adaptations to calcium source and to particle sizes of a calcium source (.35 to 1190 mu) were made within 40 d by lactating Holsteins. Starch increased and pH decreased in feces of cows fed albacar. Increasing calcium in the diet provided more buffering capacity in the gastrointestinal tract. True absorption of calcium did not differ from linearity due to source when fecal calcium was regressed on ingested calcium but did vary as a function of diet percentage. Thus, calcium retention was increased when cows were fed .9 vs. .6% calcium. These data suggest that a slow reacting (coarser) inorganic calcium source should be fed at a higher amount to optimize feed intake and milk production.

Calcium metabolism and cardiovascular function after spaceflight

NASA Technical Reports Server (NTRS)

Hatton, Daniel C.; Yue, Qi; Dierickx, Jacqueline; Roullet, Chantal; Otsuka, Keiichi; Watanabe, Mitsuaki; Coste, Sarah; Roullet, Jean Baptiste; Phanouvang, Thongchan; Orwoll, Eric;

Activity-dependent ATP-waves in the mouse neocortex are independent from astrocytic calcium waves.

PubMed

Haas, Brigitte; Schipke, Carola G; Peters, Oliver; Söhl, Goran; Willecke, Klaus; Kettenmann, Helmut

2006-02-01

In the corpus callosum, astrocytic calcium waves propagate via a mechanism involving ATP-release but not gap junctional coupling. In the present study, we report for the neocortex that calcium wave propagation depends on functional astrocytic gap junctions but is still accompanied by ATP-release. In acute slices obtained from the neocortex of mice deficient for astrocytic expression of connexin43, the calcium wave did not propagate. In contrast, in the corpus callosum and hippocampus of these mice, the wave propagated as in control animals. In addition to calcium wave propagation in astrocytes, ATP-release was recorded as a calcium signal from 'sniffer cells', a cell line expressing high-affinity purinergic receptors placed on the surface of the slice. The astrocyte calcium wave in the neocortex was accompanied by calcium signals in the 'sniffer cell' population. In the connexin43-deficient mice we recorded calcium signals from sniffer cells also in the absence of an astrocytic calcium wave. Our findings indicate that astrocytes propagate calcium signals by two separate mechanisms depending on the brain region and that ATP release can propagate within the neocortex independent from calcium waves.

Cadmium and calcium uptake in the mollusc donax rugosus and effect of a calcium channel blocker

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sidoumou, Z.; Gnassia-Barelli, M.; Romeo, M.

Donax rugosus, a common bivalve mollusc in the coastal waters of Mauritania, has been studied for trace metal concentrations as a function of sampling site (from South of Mauritania to the North of this country) and of season. In this paper, the uptake of cadmium was experimentally studied in the different organs of D. rugosus. Since metals such as cadmium, copper and mercury may alter calcium homeostasis, calcium uptake was also studied in the animals treated with cadmium. Since calcium is taken up through specific channels, it appears that metals inhibit Ca uptake by interacting with these channels in themore » plasma membrane. Cadmium and calcium have very similar atomic radii, thus cadmium may be taken up through the calcium channels, particularly through voltage-dependent channels. The uptake of cadmium and calcium by D. Rugosus was therefore also studied in the presence of the calcium channel blocker verapamil. 13 refs., 3 figs., 1 tab.« less

The activity of calcium in calcium-metal-fluoride fluxes

NASA Astrophysics Data System (ADS)

Ochifuji, Yuichiro; Tsukihashi, Fumitaka; Sano, Nobuo

1995-08-01

The standard Gibbs energy of reaction Ca (1) + O (mass pct, in Zr) = CaO (s) has been determined as follows by equilibrating molten calcium with solid zirconium in a CaO crucible: Δ G° = -64,300(±700) + 19.8(±3.5) T J/mol (1373 to 1623 K) The activities of calcium in the CaOsatd-Ca- MF2 ( M: Ca, Ba, Mg) and CaOsatd-Ca-NaF systems were measured as a function of calcium composition at high calcium contents at 1473 K on the basis of the standard Gibbs energy. The activities of calcium increase in the order of CaF2, BaF2, and MgF2 at the same calcium fraction of these fluxes. The observed activities are compared with those estimated by using the Temkin model for ionic solutions. Furthermore, the possibility of the removal of tramp elements such as tin, arsenic, antimony, bismuth, and lead from carbon-saturated iron by using calcium-metal-fluoride fluxes is discussed.

Two-pore channels function in calcium regulation in sea star oocytes and embryos

PubMed Central

Ramos, Isabela; Reich, Adrian; Wessel, Gary M.

2014-01-01

Egg activation at fertilization is an excellent process for studying calcium regulation. Nicotinic acid adenine dinucleotide-phosphate (NAADP), a potent calcium messenger, is able to trigger calcium release, likely through two-pore channels (TPCs). Concomitantly, a family of ectocellular enzymes, the ADP-ribosyl cyclases (ARCs), has emerged as being able to change their enzymatic mode from one of nucleotide cyclization in formation of cADPR to a base-exchange reaction in the generation of NAADP. Using sea star oocytes we gain insights into the functions of endogenously expressed TPCs and ARCs in the context of the global calcium signals at fertilization. Three TPCs and one ARC were found in the sea star (Patiria miniata) that were localized in the cortex of the oocytes and eggs. PmTPCs were localized in specialized secretory organelles called cortical granules, and PmARCs accumulated in a different, unknown, set of vesicles, closely apposed to the cortical granules in the egg cortex. Using morpholino knockdown of PmTPCs and PmARC in the oocytes, we found that both calcium regulators are essential for early embryo development, and that knockdown of PmTPCs leads to aberrant construction of the fertilization envelope at fertilization and changes in cortical granule pH. The calcium signals at fertilization are not significantly altered when individual PmTPCs are silenced, but the timing and shape of the cortical flash and calcium wave are slightly changed when the expression of all three PmTPCs is perturbed concomitantly, suggesting a cooperative activity among TPC isoforms in eliciting calcium signals that may influence localized physiological activities. PMID:25377554

Calcium, essential for health

PubMed

Martínez de Victoria, Emilio

2016-07-12

Calcium (Ca) is the most abundant mineral element in our body. It accounts for about 2% of body weight. The functions of calcium are: a) functions skeletal and b) regulatory functions. Bone consists of a protein matrix that mineralizes mainly with calcium (the most abundant), phosphate and magnesium, for it is essential an adequate dietary intake of Ca, phosphorus and vitamin D. The ionic Ca (Ca2+) is essential to maintain and / or perform different specialized functions of, virtually, all body cells cellular. Because of its important functions Ca2+ must be closely regulated, keeping plasma concentrations within narrow ranges. For this reason there is an accurate response against hypocalcemia or hypercalcemia in which the parathormone, calcitriol, calcitonin and vitamin K are involved. Ca intakes in the Spanish population are low in a significant percentage of the older adult’s population, especially in women. The main source of Ca in the diet is milk and milk derivatives. Green leafy vegetables, fruits and legumes can be important sources of Ca in a Mediterranean dietary pattern. The bioavailability of dietary Ca depends on physiological and dietary factors. Physiological include age, physiological status (gestation and lactation) Ca and vitamin D status and disease. Several studies relate Ca intake in the diet and various diseases, such as osteoporosis, cancer, cardiovascular disease and obesity.

Regulation of Polycystin-1 Function by Calmodulin Binding

PubMed Central

Doerr, Nicholas; Wang, Yidi; Kipp, Kevin R.; Liu, Guangyi; Benza, Jesse J.; Pletnev, Vladimir; Pavlov, Tengis S.; Staruschenko, Alexander; Mohieldin, Ashraf M.; Takahashi, Maki; Nauli, Surya M.; Weimbs, Thomas

2016-01-01

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common genetic disease that leads to progressive renal cyst growth and loss of renal function, and is caused by mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively. The PC1/PC2 complex localizes to primary cilia and can act as a flow-dependent calcium channel in addition to numerous other signaling functions. The exact functions of the polycystins, their regulation and the purpose of the PC1/PC2 channel are still poorly understood. PC1 is an integral membrane protein with a large extracytoplasmic N-terminal domain and a short, ~200 amino acid C-terminal cytoplasmic tail. Most proteins that interact with PC1 have been found to bind via the cytoplasmic tail. Here we report that the PC1 tail has homology to the regulatory domain of myosin heavy chain including a conserved calmodulin-binding motif. This motif binds to CaM in a calcium-dependent manner. Disruption of the CaM-binding motif in PC1 does not affect PC2 binding, cilia targeting, or signaling via heterotrimeric G-proteins or STAT3. However, disruption of CaM binding inhibits the PC1/PC2 calcium channel activity and the flow-dependent calcium response in kidney epithelial cells. Furthermore, expression of CaM-binding mutant PC1 disrupts cellular energy metabolism. These results suggest that critical functions of PC1 are regulated by its ability to sense cytosolic calcium levels via binding to CaM. PMID:27560828

Surface-functionalized cockle shell–based calcium carbonate aragonite polymorph as a drug nanocarrier

PubMed Central

Mohd Abd Ghafar, Syairah Liyana; Hussein, Mohd Zobir; Rukayadi, Yaya; Abu Bakar Zakaria, Md Zuki

2017-01-01

Calcium carbonate aragonite polymorph nanoparticles derived from cockle shells were prepared using surface functionalization method followed by purification steps. Size, morphology, and surface properties of the nanoparticles were characterized using transmission electron microscopy, field emission scanning electron microscopy, dynamic light scattering, zetasizer, X-ray powder diffraction, and Fourier transform infrared spectrometry techniques. The potential of surface-functionalized calcium carbonate aragonite polymorph nanoparticle as a drug-delivery agent were assessed through in vitro drug-loading test and drug-release test. Transmission electron microscopy, field emission scanning electron microscopy, and particle size distribution analyses revealed that size, morphology, and surface characterization had been improved after surface functionalization process. Zeta potential of the nanoparticles was found to be increased, thereby demonstrating better dispersion among the nanoparticles. Purification techniques showed a further improvement in the overall distribution of nanoparticles toward more refined size ranges <100 nm, which specifically favored drug-delivery applications. The purity of the aragonite phase and their chemical analyses were verified by X-ray powder diffraction and Fourier transform infrared spectrometry studies. In vitro biological response of hFOB 1.19 osteoblast cells showed that surface functionalization could improve the cytotoxicity of cockle shell–based calcium carbonate aragonite nanocarrier. The sample was also sensitive to pH changes and demonstrated good abilities to load and sustain in vitro drug. This study thus indicates that calcium carbonate aragonite polymorph nanoparticles derived from cockle shells, a natural biomaterial, with modified surface characteristics are promising and can be applied as efficient carriers for drug delivery. PMID:28572724

Data on PKO biodiesel production using CaO catalyst from Turkey bones.

PubMed

Ayoola, A A; Fayomi, O S I; Usoro, I F

2018-08-01

In this research paper the production of biodiesel from palm kernel oil (PKO) using CaO obtained from waste turkey bones (WTB) and analytical grade calcium oxide was investigated. Treated WTB was reduced to fine particulate size of <150 µm and then calcinated at 800 °C for 3 h to increase its catalytic activity by its conversion from Calcium phosphate hydroxide (Ca 10 P 6 O 26 H 2 ) to CaO. X-ray diffraction (XRD) and X-ray fluorescent (XRF) analysis of the analytical grade CaO, uncalcined and calcined WTB were carried out to establish their elemental chemical composition. The transesterification reaction between the triglyceride of palm kernel oil (PKO) and methanol was carried out at a constant agitation speed of 600 rpm and temperature of 65 °C, with varied methanol to oil molar ratio (8-14), catalyst concentration (1-7 wt/wt%) and the reaction time (1-3 h). Minitab 17 software (using response surface method) was employed for the design of experiment and statistical analysis required in the transesterification process of biodiesel production. The qualities of the biodiesel produced were assessed and the results obtained showed conformity of the biodiesel produced to the ASTM standard for biodiesel.

Functionally Graded Multifunctional Hybrid Composites for Extreme Environments

DTIC Science & Technology

2010-02-01

Develop multifunctional FGHC with multiple layers: a ceramic thermal barrier layer, a graded ceramic /metal composite (GCMeC) layer and a high...AFOSR-MURI Functionally Graded Hybrid Composites Actively Cooled PMC White (UIUC) FGHC Fabrication Team Graded Ceramic Metal Composites (GCMeC...Composites Fabrication and Characterization of Bulk Ceramic MAX Phase and MAX–Metal Composites AFOSR-MURI Functionally Graded Hybrid Composites Mn

Alteration of Motor Network Function Following Injury

DTIC Science & Technology

2012-10-01

mechanisms from neuromodulator- dependent corre- lations of mRNA and conductance levels. Ion channel conductances are correlated across channel types...de- pendent on intracellular calcium signaling mechanisms that depend on the release of intracellular calcium stores. Because relatively rapid changes...changes in K current mag- nitudes are independently regulated by distinct mechanisms . Compensatory increases in IKCa are calcium- dependent and due, at

Maladjustment of kidneys to microgravity: Design of measures to reduce the loss of calcium

NASA Technical Reports Server (NTRS)

Nechay, Bohdan R.

1989-01-01

Losses of skeletal calcium and body fluids occur during prolonged exposure to microgravity. The kidney plays a major role in regulating the physiological functions involved. Relative to this regulatory function, the kidney performs three operations: filtration of blood plasma through the glomeruli, reabsorption, and secretion of fluid and electrolytes so that needed components are retained and only waste is eliminated in the urine. Using data published in Biomedical Results from Skylab, researchers performed new calculations that reflect more directly the operations of the kidney in the handling of calcium, sodium, chloride, potassium and phosphate during space flight. These calculations revealed that the fraction of filtered calcium that was rejected by renal tubules and excreted in the urine increased by 71 percent, from 1.77 percent (preflight) to 3.02 percent (inflight) of the filtered load. This represents a large absolute increase because the total filtered amount is huge. Because the tubular rejection fraction of other ions increased relatively less than that of calcium, researchers postulate the inflight development of a specific renal defect that causes an excessive loss of calcium in urine and thereby contributes to the weakening of bones.

Protein-specific localization of a rhodamine-based calcium-sensor in living cells.

PubMed

Best, Marcel; Porth, Isabel; Hauke, Sebastian; Braun, Felix; Herten, Dirk-Peter; Wombacher, Richard

2016-06-28

A small synthetic calcium sensor that can be site-specifically coupled to proteins in living cells by utilizing the bio-orthogonal HaloTag labeling strategy is presented. We synthesized an iodo-derivatized BAPTA chelator with a tetramethyl rhodamine fluorophore that allows further modification by Sonogashira cross-coupling. The presented calcium sensitive dye shows a 200-fold increase in fluorescence upon calcium binding. The derivatization with an aliphatic linker bearing a terminal haloalkane-function by Sonogashira cross-coupling allows the localization of the calcium sensor to Halo fusion proteins which we successfully demonstrate in in vitro and in vivo experiments. The herein reported highly sensitive tetramethyl rhodamine based calcium indicator, which can be selectively localized to proteins, is a powerful tool to determine changes in calcium levels inside living cells with spatiotemporal resolution.

Trace Element Levels and Cognitive Function in Rural Elderly Chinese

PubMed Central

Gao, Sujuan; Jin, Yinlong; Unverzagt, Frederick W.; Ma, Feng; Hall, Kathleen S.; Murrell, Jill R.; Cheng, Yibin; Shen, Jianzhao; Ying, Bo; Ji, Rongdi; Matesan, Janetta; Liang, Chaoke; Hendrie, Hugh C.

2009-01-01

Background Trace elements are involved in metabolic processes and oxidation-reduction reactions in the central nervous system and could have a possible effect on cognitive function. The relationship between trace elements measured in individual biological samples and cognitive function in an elderly population had not been investigated extensively. Methods The participant population is part of a large cohort study of 2000 rural elderly Chinese persons. Six cognitive assessment tests were used to evaluate cognitive function in this population, and a composite score was created to represent global cognitive function. Trace element levels of aluminum, calcium, cadmium, copper, iron, lead, and zinc were analyzed in plasma samples of 188 individuals who were randomly selected and consented to donating fasting blood. Analysis of covariance models were used to assess the association between each trace element and the composite cognitive score adjusting for demographics, medical history of chronic diseases, and the apolipoprotein E (APOE) genotype. Results Three trace elements—calcium, cadmium, and copper—were found to be significantly related to the composite cognitive score. Increasing plasma calcium level was associated with higher cognitive score (p < .0001). Increasing cadmium and copper, in contrast, were significantly associated with lower composite score (p = .0044 and p = .0121, respectively). Other trace elements did not show significant association with the composite cognitive score. Conclusions Our results suggest that calcium, cadmium, and copper may be associated with cognitive function in the elderly population. PMID:18559640

Trace element levels and cognitive function in rural elderly Chinese.

PubMed

Gao, Sujuan; Jin, Yinlong; Unverzagt, Frederick W; Ma, Feng; Hall, Kathleen S; Murrell, Jill R; Cheng, Yibin; Shen, Jianzhao; Ying, Bo; Ji, Rongdi; Matesan, Janetta; Liang, Chaoke; Hendrie, Hugh C

2008-06-01

Trace elements are involved in metabolic processes and oxidation-reduction reactions in the central nervous system and could have a possible effect on cognitive function. The relationship between trace elements measured in individual biological samples and cognitive function in an elderly population had not been investigated extensively. The participant population is part of a large cohort study of 2000 rural elderly Chinese persons. Six cognitive assessment tests were used to evaluate cognitive function in this population, and a composite score was created to represent global cognitive function. Trace element levels of aluminum, calcium, cadmium, copper, iron, lead, and zinc were analyzed in plasma samples of 188 individuals who were randomly selected and consented to donating fasting blood. Analysis of covariance models were used to assess the association between each trace element and the composite cognitive score adjusting for demographics, medical history of chronic diseases, and the apolipoprotein E (APOE) genotype. Three trace elements-calcium, cadmium, and copper-were found to be significantly related to the composite cognitive score. Increasing plasma calcium level was associated with higher cognitive score (p <.0001). Increasing cadmium and copper, in contrast, were significantly associated with lower composite score (p =.0044 and p =.0121, respectively). Other trace elements did not show significant association with the composite cognitive score. Our results suggest that calcium, cadmium, and copper may be associated with cognitive function in the elderly population.

Behavioral and Functional Assays for Investigating Mechanisms of Noxious Cold Detection and Multimodal Sensory Processing in Drosophila Larvae

PubMed Central

Patel, Atit A.; Cox, Daniel N.

2017-01-01

To investigate cellular, molecular and behavioral mechanisms of noxious cold detection, we developed cold plate behavioral assays and quantitative means for evaluating the predominant noxious cold-evoked contraction behavior. To characterize neural activity in response to noxious cold, we implemented a GCaMP6-based calcium imaging assay enabling in vivo studies of intracellular calcium dynamics in intact Drosophila larvae. We identified Drosophila class III multidendritic (md) sensory neurons as multimodal sensors of innocuous mechanical and noxious cold stimuli and to dissect the mechanistic bases of multimodal sensory processing we developed two independent functional assays. First, we developed an optogenetic dose response assay to assess whether levels of neural activation contributes to the multimodal aspects of cold sensitive sensory neurons. Second, we utilized CaMPARI, a photo-switchable calcium integrator that stably converts fluorescence from green to red in presence of high intracellular calcium and photo-converting light, to assess in vivo functional differences in neural activation levels between innocuous mechanical and noxious cold stimuli. These novel assays enable investigations of behavioral and functional roles of peripheral sensory neurons and multimodal sensory processing in Drosophila larvae. PMID:28835907

Genetic disruption of voltage-gated calcium channels in psychiatric and neurological disorders

PubMed Central

Heyes, Samuel; Pratt, Wendy S.; Rees, Elliott; Dahimene, Shehrazade; Ferron, Laurent; Owen, Michael J.; Dolphin, Annette C.

2015-01-01

This review summarises genetic studies in which calcium channel genes have been connected to the spectrum of neuropsychiatric syndromes, from bipolar disorder and schizophrenia to autism spectrum disorders and intellectual impairment. Among many other genes, striking numbers of the calcium channel gene superfamily have been implicated in the aetiology of these diseases by various DNA analysis techniques. We will discuss how these relate to the known monogenic disorders associated with point mutations in calcium channels. We will then examine the functional evidence for a causative link between these mutations or single nucleotide polymorphisms and the disease processes. A major challenge for the future will be to translate the expanding psychiatric genetic findings into altered physiological function, involvement in the wider pathology of the diseases, and what potential that provides for personalised and stratified treatment options for patients. PMID:26386135

Grading of Student's Attainment: Purposes and Functions.

ERIC Educational Resources Information Center

Lysne, Anders

1984-01-01

Traces the history of grading and discusses the complex problem of evaluation and grading of student achievement. Reviews the various reference measures and notes the type of functions grades are supposed to serve. Cites seven alternatives to traditional grading. Concludes that "grades are the tail that wags the dog." (BRR)

TMEM16A is associated with voltage-gated calcium channels in mouse retina and its function is disrupted upon mutation of the auxiliary α2δ4 subunit

PubMed Central

Caputo, Antonella; Piano, Ilaria; Demontis, Gian Carlo; Bacchi, Niccolò; Casarosa, Simona; Santina, Luca Della; Gargini, Claudia

2015-01-01

Photoreceptors rely upon highly specialized synapses to efficiently transmit signals to multiple postsynaptic targets. Calcium influx in the presynaptic terminal is mediated by voltage-gated calcium channels (VGCC). This event triggers neurotransmitter release, but also gates calcium-activated chloride channels (TMEM), which in turn regulate VGCC activity. In order to investigate the relationship between VGCC and TMEM channels, we analyzed the retina of wild type (WT) and Cacna2d4 mutant mice, in which the VGCC auxiliary α2δ4 subunit carries a nonsense mutation, disrupting the normal channel function. Synaptic terminals of mutant photoreceptors are disarranged and synaptic proteins as well as TMEM16A channels lose their characteristic localization. In parallel, calcium-activated chloride currents are impaired in rods, despite unaltered TMEM16A protein levels. Co-immunoprecipitation revealed the interaction between VGCC and TMEM16A channels in the retina. Heterologous expression of these channels in tsA-201 cells showed that TMEM16A associates with the CaV1.4 subunit, and the association persists upon expression of the mutant α2δ4 subunit. Collectively, our experiments show association between TMEM16A and the α1 subunit of VGCC. Close proximity of these channels allows optimal function of the photoreceptor synaptic terminal under physiological conditions, but also makes TMEM16A channels susceptible to changes occurring to calcium channels. PMID:26557056

A Mechanism of Intracellular P2X Receptor Activation*

PubMed Central

Sivaramakrishnan, Venketesh; Fountain, Samuel J.

2012-01-01

P2X receptors (P2XRs) are ATP-activated calcium-permeable ligand-gated ion channels traditionally viewed as sensors of extracellular ATP during diverse physiological processes including pain, inflammation, and taste. However, in addition to a cell surface residency P2XRs also populate the membranes of intracellular compartments, including mammalian lysosomes, phagosomes, and the contractile vacuole (CV) of the amoeba Dictyostelium. The function of intracellular P2XRs is unclear and represents a major gap in our understanding of ATP signaling. Here, we exploit the genetic versatility of Dictyostelium to investigate the effects of physiological concentrations of ATP on calcium signaling in isolated CVs. Within the CV, an acidic calcium store, P2XRs are orientated to sense luminal ATP. Application of ATP to isolated vacuoles leads to luminal translocation of ATP and release of calcium. Mechanisms of luminal ATP translocation and ATP-evoked calcium release share common pharmacology, suggesting that they are linked processes. The ability of ATP to mobilize stored calcium is reduced in vacuoles isolated from P2XAR knock-out amoeba and ablated in cells devoid of P2XRs. Pharmacological inhibition of luminal ATP translocation or depletion of CV calcium attenuates CV function in vivo, manifesting as a loss of regulatory cell volume decrease following osmotic swelling. We propose that intracellular P2XRs regulate vacuole activity by acting as calcium release channels, activated by translocation of ATP into the vacuole lumen. PMID:22736763

Genetically encoded calcium indicators for studying long-term calcium dynamics during apoptosis.

PubMed

Garcia, M Iveth; Chen, Jessica J; Boehning, Darren

2017-01-01

Intracellular calcium release is essential for regulating almost all cellular functions. Specific spatio-temporal patterns of cytosolic calcium elevations are critical determinants of cell fate in response to pro-apoptotic cellular stressors. As the apoptotic program can take hours or days, measurement of long-term calcium dynamics are essential for understanding the mechanistic role of calcium in apoptotic cell death. Due to the technical limitations of using calcium-sensitive dyes to measure cytosolic calcium little is known about long-term calcium dynamics in living cells after treatment with apoptosis-inducing drugs. Genetically encoded calcium indicators could potentially overcome some of the limitations of calcium-sensitive dyes. Here, we compared the performance of the genetically encoded calcium indicators GCaMP6s and GCaMP6f with the ratiometric dye Fura-2. GCaMP6s performed as well or better than Fura-2 in detecting agonist-induced calcium transients. We then examined the utility of GCaMP6s for continuously measuring apoptotic calcium release over the course of ten hours after treatment with staurosporine. We found that GCaMP6s was suitable for measuring apoptotic calcium release over long time courses and revealed significant heterogeneity in calcium release dynamics in individual cells challenged with staurosporine. Our results suggest GCaMP6s is an excellent indicator for monitoring long-term changes cytosolic calcium during apoptosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel Peptide with Specific Calcium-Binding Capacity from Schizochytrium sp. Protein Hydrolysates and Calcium Bioavailability in Caco-2 Cells

PubMed Central

Cai, Xixi; Lin, Jiaping; Wang, Shaoyun

2016-01-01

Peptide-calcium can probably be a suitable supplement to improve calcium absorption in the human body. In this study, a specific peptide Phe-Tyr (FY) with calcium-binding capacity was purified from Schizochytrium sp. protein hydrolysates through gel filtration chromatography and reversed phase HPLC. The calcium-binding capacity of FY reached 128.77 ± 2.57 μg/mg. Results of ultraviolet spectroscopy, fluorescence spectroscopy, and infrared spectroscopy showed that carboxyl groups, amino groups, and amido groups were the major chelating sites. FY-Ca exhibited excellent thermal stability and solubility, which were beneficial to be absorbed and transported in the basic intestinal tract of the human body. Moreover, the calcium bioavailability in Caco-2 cells showed that FY-Ca could enhance calcium uptake efficiency by more than three times when compared with CaCl2, and protect calcium ions against dietary inhibitors, such as tannic acid, oxalate, phytate, and Zn2+. Our findings further the progress of algae-based peptide-calcium, suggesting that FY-Ca has the potential to be developed as functionally nutraceutical additives. PMID:28036002

A randomised study to compare salivary pH, calcium, phosphate and calculus formation after using anticavity dentifrices containing Recaldent(®) and functionalized tri-calcium phosphate.

PubMed

Sharma, Ena; Vishwanathamurthy, Ramesh Alampalli; Nadella, Manjari; Savitha, A N; Gundannavar, Gayatri; Hussain, M Ahad

2012-10-01

The aim of this study was to estimate the pH of saliva, concentration of calcium and inorganic phosphate, and calculus formation before and after usage of Recaldent(®) (GC Tooth Mousse Plus™), Functionalized Tricalcium Phosphate (3M ESPE ClinPro™ Tooth Crème) and standard dentifrice (Colgate dental cream). Randomized double-blind study. A total of 50 subjects were recruited, the subjects were assessed at their first visit, on the 21(st) day and on the 42(nd) day. At the first visit, scaling was carried out and oral hygiene instructions were given. After 21 days, the subjects were given coded dentifrices where the operator and the subjects both were unaware of the type of dentifrice. Clinical parameters assessed were Plaque index, Gingival index, and Calculus index. Salivary samples were obtained to measure calcium, phosphate levels, and pH at 21(st) day and 42(nd) day. ANOVA test, t-test, Mann-Whitney test, Kruskal-Wallis test. The mean salivary calcium level and mean salivary phosphate level were higher in Group III (functionalized tricalcium phosphate (3M ESPE ClinPro™ Tooth Creme) as compared to Group II (Recaldent(®) GC Tooth Mousse Plus™) and Group I (Colgate dental cream) on the 42(nd) day after using dentifrices, which was statistically significant. This showed that the usage of remineralizing dentifrices led to an increase in the salivary calcium, phosphate, and pH but it did not reach the level of super saturation of the ions caused by elevated pH which could lead to calculus formation. Thought here was a statistically significant increase in salivary calcium and phosphate level in all three groups from baseline to 42(nd) day, there was no calculus formation.

Effect of Angiotensin-Converting Enzyme Inhibitor/Calcium Antagonist Combination Therapy on Renal Function in Hypertensive Patients With Chronic Kidney Disease: Chikushi Anti-Hypertension Trial - Benidipine and Perindopril.

PubMed

Okuda, Tetsu; Okamura, Keisuke; Shirai, Kazuyuki; Urata, Hidenori

2018-02-01

Appropriate blood pressure control suppresses progression of chronic kidney disease (CKD). If an angiotensin-converting enzyme (ACE) inhibitor is ineffective, adding a calcium antagonist is recommended. We compared the long-term effect of two ACE inhibitor/calcium antagonist combinations on renal function in hypertensive patients with CKD. Patients who failed to achieve the target blood pressure (systolic/diastolic: < 130/80 mm Hg) with perindopril monotherapy were randomized to either combined therapy with perindopril and the L-type calcium antagonist amlodipine (group A) or perindopril and the T/L type calcium antagonist benidipine (group B). The primary endpoint was the change of the estimated glomerular filtration rate (eGFR) after 2 years. Eligible patients had a systolic pressure ≥ 130 mm Hg and/or diastolic pressure ≥ 80 mm Hg and CKD (urine protein (+) or higher, eGFR < 60 min/mL/1.73 m 2 ). After excluding 38 patients achieving the target blood pressure with perindopril monotherapy, 121 patients were analyzed (62 in group A and 59 in group B). Blood pressure decreased significantly in both groups, but there was no significant change of the eGFR. However, among patients with diabetes, eGFR unchanged in group B (n = 37, 59.1 ± 15.1 vs. 61.2 ± 27.9, P = 0.273), whereas decreased significantly in group A (n = 31, 57.3 ± 16.0 vs. 53.7 ± 16.7, P = 0.005). In hypertensive patients with diabetic nephropathy, combined therapy with an ACE inhibitor and T/L type calcium antagonist may prevent deterioration of renal function more effectively than an ACE inhibitor/L type calcium antagonist combination.

Structural basis for the differential effects of CaBP1 and calmodulin on Ca(V)1.2 calcium-dependent inactivation.

PubMed

Findeisen, Felix; Minor, Daniel L

2010-12-08

Calcium-binding protein 1 (CaBP1), a calmodulin (CaM) homolog, endows certain voltage-gated calcium channels (Ca(V)s) with unusual properties. CaBP1 inhibits Ca(V)1.2 calcium-dependent inactivation (CDI) and introduces calcium-dependent facilitation (CDF). Here, we show that the ability of CaBP1 to inhibit Ca(V)1.2 CDI and induce CDF arises from interaction between the CaBP1 N-lobe and interlobe linker residue Glu94. Unlike CaM, where functional EF hands are essential for channel modulation, CDI inhibition does not require functional CaBP1 EF hands. Furthermore, CaBP1-mediated CDF has different molecular requirements than CaM-mediated CDF. Overall, the data show that CaBP1 comprises two structural modules having separate functions: similar to CaM, the CaBP1 C-lobe serves as a high-affinity anchor that binds the Ca(V)1.2 IQ domain at a site that overlaps with the Ca²+/CaM C-lobe site, whereas the N-lobe/linker module houses the elements required for channel modulation. Discovery of this division provides the framework for understanding how CaBP1 regulates Ca(V)s. Copyright © 2010 Elsevier Ltd. All rights reserved.

Structural basis for the differential effects of CaBP1 and calmodulin on CaV1.2 calcium-dependent inactivation

PubMed Central

Findeisen, Felix; Minor, Daniel L.

2010-01-01

Calcium-binding protein 1 (CaBP1), a calmodulin (CaM) homolog, endows certain voltage-gated calcium channels (CaVs) with unusual properties. CaBP1 inhibits CaV1.2 calcium-dependent inactivation (CDI) and introduces calcium-dependent facilitation (CDF). Here, we show that the ability of CaBP1 to inhibit CaV1.2 CDI and induce CDF arises from interaction between the CaBP1 N-lobe and interlobe linker residue Glu94. Unlike CaM, where functional EF hands are essential for channel modulation, CDI inhibition does not require functional CaBP1 EF-hands. Furthermore, CaBP1-mediated CDF has different molecular requirements than CaM-mediated CDF. Overall, the data show that CaBP1 comprises two structural modules having separate functions: similar to CaM, the CaBP1 C-lobe serves as a high-affinity anchor that binds the CaV1.2 IQ domain at a site that overlaps with the Ca2+/CaM C-lobe site, whereas the N-lobe/linker module houses the elements required for channel modulation. Discovery of this division provides the framework for understanding how CaBP1 regulates CaVs. PMID:21134641

Presynaptic muscarinic receptors, calcium channels, and protein kinase C modulate the functional disconnection of weak inputs at polyinnervated neonatal neuromuscular synapses.

PubMed

Santafe, M M; Garcia, N; Lanuza, M A; Tomàs, M; Besalduch, N; Tomàs, J

2009-04-01

We studied the relation among calcium inflows, voltage-dependent calcium channels (VDCC), presynaptic muscarinic acetylcholine receptors (mAChRs), and protein kinase C (PKC) activity in the modulation of synapse elimination. We used intracellular recording to determine the synaptic efficacy in dually innervated endplates of the levator auris longus muscle of newborn rats during axonal competition in the postnatal synaptic elimination period. In these dual junctions, the weak nerve terminal was potentiated by partially reducing calcium entry (P/Q-, N-, or L-type VDCC-specific block or 500 muM magnesium ions), M1- or M4-type selective mAChR block, or PKC block. Moreover, reducing calcium entry or blocking PKC or mAChRs results in unmasking functionally silent nerve endings that now recover neurotransmitter release. Our results show interactions between these molecules and indicate that there is a release inhibition mechanism based on an mAChR-PKC-VDCC intracellular cascade. When it is fully active in certain weak motor axons, it can depress ACh release and even disconnect synapses. We suggest that this mechanism plays a central role in the elimination of redundant neonatal synapses, because functional axonal withdrawal can indeed be reversed by mAChRs, VDCCs, or PKC block.

Experiment K-6-19. Pineal physiology in microgravity: Relation to rat gonadal function

NASA Technical Reports Server (NTRS)

Holley, D.; Soliman, M. R. I.; Kaddis, F.; Markley, C.; Krasnov, I.

1990-01-01

One of the most interesting concomitants to spaceflight and exposure to microgravity has been the disturbing alteration in calcium metabolism and resulting skeletal effects. It was recognized as early as 1685 (cited in Kitay and Altschule, 1954) that the pineal of humans calcified with age. However, little can be found in the literature relating calcification and pineal function. Given the link between exposure to microgravity and perturbation of calcium metabolism and the fact that the pineal is apparently one of the only soft tissues to calcify, researchers examined pineal calcium content following the spaceflight. Researchers concluded that the spaceflight resulted in a stress response as indicated by adrenal hypertrophy, that gonadal function was compromised, and that the pineal may be linked as part of the mechanism of the responses noted.

The fate of calcium carbonate nanoparticles administered by oral route: absorption and their interaction with biological matrices

PubMed Central

Lee, Jeong-A; Kim, Mi-Kyung; Kim, Hyoung-Mi; Lee, Jong Kwon; Jeong, Jayoung; Kim, Young-Rok; Oh, Jae-Min; Choi, Soo-Jin

2015-01-01

Background Orally administered particles rapidly interact with biological fluids containing proteins, enzymes, electrolytes, and other biomolecules to eventually form particles covered by a corona, and this corona potentially affects particle uptake, fate, absorption, distribution, and elimination in vivo. This study explored relationships between the biological interactions of calcium carbonate particles and their biokinetics. Methods We examined the effects of food grade calcium carbonates of different particle size (nano [N-Cal] and bulk [B-Cal]: specific surface areas of 15.8 and 0.83 m2/g, respectively) on biological interactions in in vitro simulated physiological fluids, ex vivo biofluids, and in vivo in gastrointestinal fluid. Moreover, absorption and tissue distribution of calcium carbonates were evaluated following a single dose oral administration to rats. Results N-Cal interacted more with biomatrices than bulk materials in vitro and ex vivo, as evidenced by high fluorescence quenching ratios, but it did not interact more actively with biomatrices in vivo. Analysis of coronas revealed that immunoglobulin, apolipoprotein, thrombin, and fibrinogen, were the major corona proteins, regardless of particle size. A biokinetic study revealed that orally delivered N-Cal was more rapidly absorbed into the blood stream than B-Cal, but no significant differences were observed between the two in terms of absorption efficiencies or tissue distributions. Both calcium carbonates were primarily present as particulate forms in gastrointestinal fluids but enter the circulatory system in dissolved Ca2+, although both types showed partial phase transformation to dicalcium phosphate dihydrate. Relatively low dissolution (about 4%), no remarkable protein–particle interaction, and the major particulate fate of calcium carbonate in vivo gastrointestinal fluids can explain its low oral absorption (about 4%) regardless of particle size. Conclusion We conclude that calcium carbonate nanoparticles can act more actively with biological matrices in vitro and ex vivo, but that in vivo, their biological interactions and biokinetics are not affected by particle size. PMID:25848250

The fate of calcium carbonate nanoparticles administered by oral route: absorption and their interaction with biological matrices.

PubMed

Lee, Jeong-A; Kim, Mi-Kyung; Kim, Hyoung-Mi; Lee, Jong Kwon; Jeong, Jayoung; Kim, Young-Rok; Oh, Jae-Min; Choi, Soo-Jin

2015-01-01

Orally administered particles rapidly interact with biological fluids containing proteins, enzymes, electrolytes, and other biomolecules to eventually form particles covered by a corona, and this corona potentially affects particle uptake, fate, absorption, distribution, and elimination in vivo. This study explored relationships between the biological interactions of calcium carbonate particles and their biokinetics. We examined the effects of food grade calcium carbonates of different particle size (nano [N-Cal] and bulk [B-Cal]: specific surface areas of 15.8 and 0.83 m(2)/g, respectively) on biological interactions in in vitro simulated physiological fluids, ex vivo biofluids, and in vivo in gastrointestinal fluid. Moreover, absorption and tissue distribution of calcium carbonates were evaluated following a single dose oral administration to rats. N-Cal interacted more with biomatrices than bulk materials in vitro and ex vivo, as evidenced by high fluorescence quenching ratios, but it did not interact more actively with biomatrices in vivo. Analysis of coronas revealed that immunoglobulin, apolipoprotein, thrombin, and fibrinogen, were the major corona proteins, regardless of particle size. A biokinetic study revealed that orally delivered N-Cal was more rapidly absorbed into the blood stream than B-Cal, but no significant differences were observed between the two in terms of absorption efficiencies or tissue distributions. Both calcium carbonates were primarily present as particulate forms in gastrointestinal fluids but enter the circulatory system in dissolved Ca(2+), although both types showed partial phase transformation to dicalcium phosphate dihydrate. Relatively low dissolution (about 4%), no remarkable protein-particle interaction, and the major particulate fate of calcium carbonate in vivo gastrointestinal fluids can explain its low oral absorption (about 4%) regardless of particle size. We conclude that calcium carbonate nanoparticles can act more actively with biological matrices in vitro and ex vivo, but that in vivo, their biological interactions and biokinetics are not affected by particle size.

Calcium permeable AMPA receptors and autoreceptors in external tufted cells of rat olfactory bulb

PubMed Central

Ma, Jie; Lowe, Graeme

2007-01-01

Glomeruli are functional units of the olfactory bulb responsible for early processing of odor information encoded by single olfactory receptor genes. Glomerular neural circuitry includes numerous external tufted (ET) cells whose rhythmic burst firing may mediate synchronization of bulbar activity with the inhalation cycle. Bursting is entrained by glutamatergic input from olfactory nerve terminals, so specific properties of ionotropic glutamate receptors on ET cells are likely to be important determinants of olfactory processing. Particularly intriguing is recent evidence that α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors of juxta-glomerular neurons may permeate calcium. This could provide a novel pathway for regulating ET cell signaling. We tested the hypothesis that ET cells express functional calcium-permeable AMPA receptors. In rat olfactory bulb slices, excitatory postsynaptic currents (EPSCs) in ET cells were evoked by olfactory nerve shock, and by uncaging glutamate. We found attenuation of AMPA/kainate EPSCs by 1-naphthyl acetyl-spermine (NAS), an open-channel blocker specific for calcium permeable AMPA receptors. Cyclothiazide strongly potentiated EPSCs, indicating a major contribution from AMPA receptors. The current-voltage (I-V) relation of uncaging EPSCs showed weak inward rectification which was lost after > ~ 10 min of whole-cell dialysis, and was absent in NAS. In kainate-stimulated slices, Co2+ ions permeated cells of the glomerular layer. Large AMPA EPSCs were accompanied by fluorescence signals in fluo-4 loaded cells, suggesting calcium permeation. Depolarizing pulses evoked slow tail currents with pharmacology consistent with involvement of calcium permeable AMPA autoreceptors. Tail currents were abolished by Cd2+ and NBQX, and were sensitive to NAS block. Glutamate autoreceptors were confirmed by uncaging intracellular calcium to evoke a large inward current. Our results provide evidence that calcium permeable AMPA receptors reside on ET cells, and are divided into at least two functionally distinct pools – postsynaptic receptors at olfactory nerve synaptic terminals, and autoreceptors sensitive to glutamate released from dendrodendritic synapses. PMID:17156930

Regulatory effect of chrysin on expression of lenticular calcium transporters, calpains, and apoptotic-cascade components in selenite-induced cataract

PubMed Central

Sundararajan, Mahalingam; Thomas, Philip A.; Teresa, P. Archana; Anbukkarasi, Muniyandi

2016-01-01

Purpose Selenite-induced cataract is associated with oxidative stress, loss of calcium homeostasis, activation of calpain enzymes, and apoptotic cell death in the lens. An evaluation of naturally occurring antioxidants that also restrict calcium influx into the lens and calpain activation and thus prevent lenticular cell death may lead to the development of safe and effective anticataractogenic drugs. This study focuses on a naturally occurring flavone, chrysin, and its efficacy in preventing cataractogenic changes in in vitro cultured Wistar rat lenses. Methods Lenses from Wistar rats incubated for 24 h at 37 °C in Dulbecco’s modified Eagle’s medium (DMEM) were categorized into four main groups: Group I (control, incubated in DMEM alone); Group II (selenite-challenged and untreated, incubated in DMEM that contained 100 µM/ml of sodium selenite only); Group III (selenite-challenged and chrysin-treated, incubated in DMEM that contained sodium selenite [100 µM/ml of DMEM] and chrysin [200 µM/ml of DMEM]); and Group IV (chrysin-treated, incubated in DMEM that contained chrysin [200 µM/ml of DMEM] only). The Group III (selenite-challenged and chrysin-treated) lenses were further categorized into five sub-groups: Group IIIa (incubated for 24 h in DMEM that contained sodium selenite and chrysin added simultaneously), Group IIIb (first incubated for 2 h in DMEM that contained chrysin only and then for up to 24 h in fresh DMEM that contained sodium selenite only), Group IIIc (first incubated for 30 min in DMEM that contained sodium selenite only and subsequently for up to 24 h in DMEM that contained chrysin only), and Groups IIId and IIIe (first incubated for 1 h and 2 h, respectively, in DMEM that contained sodium selenite only and subsequently for up to 24 h in DMEM that contained chrysin only). Results Gross morphological assessment revealed dense opacification (Grade +++) in the selenite-challenged, untreated lenses (Group II); however, seven of the eight selenite-challenged and simultaneously chrysin-treated (Group IIIa) lenses showed no opacification (Grade 0) after 24 h incubation, while the remaining single lens exhibited only a slight degree of opacification (Grade +). In the Group IIIa lenses, the reduced glutathione, protein sulfhydryl, and malondialdehyde concentrations appeared to have been maintained at near-normal levels. The mean lenticular concentration of calcium was significantly lower in the Group IIIa lenses than that in the Group II lenses and approximated the values observed in the normal control (Group I) lenses. The Group IIIa lenses also exhibited significantly (p<0.05) higher mean lenticular activity of calpain, significantly higher mean mRNA transcript levels of genes that encode m-calpain and lenticular preferred calpain (Lp82), and significantly higher mean levels of the m-calpain and Lp82 proteins than the corresponding values in the Group II lenses. Casein zymography results suggested that chrysin prevented calpain activation and autolysis. Significantly (p<0.05) lower mean levels of mRNA transcripts of the genes that encode calcium transporter proteins (plasma membrane Ca2+-ATPase-1 and sarco/endoplasmic reticulum Ca2+-ATPase-2) and lenticular apoptotic-cascade proteins (early growth response protein-1, caspase-3, caspase-8, and caspase-9) and significantly (p<0.05) lower mean concentrations of the proteins themselves were seen in the Group IIIa rat lenses in comparison to the values noted in the Group II rat lenses. Conclusions Chrysin appears to prevent selenite-induced cataractogenesis in vitro by maintaining the redox system components at near-normal levels and by preventing the abnormal expression of several lenticular calcium transporters and apoptotic-cascade proteins, thus preventing accumulation of calcium and subsequent calpain activation and lenticular cell death in cultured Wistar rat lenses. PMID:27168717

Regulatory effect of chrysin on expression of lenticular calcium transporters, calpains, and apoptotic-cascade components in selenite-induced cataract.

PubMed

Sundararajan, Mahalingam; Thomas, Philip A; Teresa, P Archana; Anbukkarasi, Muniyandi; Geraldine, Pitchairaj

2016-01-01

Selenite-induced cataract is associated with oxidative stress, loss of calcium homeostasis, activation of calpain enzymes, and apoptotic cell death in the lens. An evaluation of naturally occurring antioxidants that also restrict calcium influx into the lens and calpain activation and thus prevent lenticular cell death may lead to the development of safe and effective anticataractogenic drugs. This study focuses on a naturally occurring flavone, chrysin, and its efficacy in preventing cataractogenic changes in in vitro cultured Wistar rat lenses. Lenses from Wistar rats incubated for 24 h at 37 °C in Dulbecco's modified Eagle's medium (DMEM) were categorized into four main groups: Group I (control, incubated in DMEM alone); Group II (selenite-challenged and untreated, incubated in DMEM that contained 100 µM/ml of sodium selenite only); Group III (selenite-challenged and chrysin-treated, incubated in DMEM that contained sodium selenite [100 µM/ml of DMEM] and chrysin [200 µM/ml of DMEM]); and Group IV (chrysin-treated, incubated in DMEM that contained chrysin [200 µM/ml of DMEM] only). The Group III (selenite-challenged and chrysin-treated) lenses were further categorized into five sub-groups: Group IIIa (incubated for 24 h in DMEM that contained sodium selenite and chrysin added simultaneously), Group IIIb (first incubated for 2 h in DMEM that contained chrysin only and then for up to 24 h in fresh DMEM that contained sodium selenite only), Group IIIc (first incubated for 30 min in DMEM that contained sodium selenite only and subsequently for up to 24 h in DMEM that contained chrysin only), and Groups IIId and IIIe (first incubated for 1 h and 2 h, respectively, in DMEM that contained sodium selenite only and subsequently for up to 24 h in DMEM that contained chrysin only). Gross morphological assessment revealed dense opacification (Grade +++) in the selenite-challenged, untreated lenses (Group II); however, seven of the eight selenite-challenged and simultaneously chrysin-treated (Group IIIa) lenses showed no opacification (Grade 0) after 24 h incubation, while the remaining single lens exhibited only a slight degree of opacification (Grade +). In the Group IIIa lenses, the reduced glutathione, protein sulfhydryl, and malondialdehyde concentrations appeared to have been maintained at near-normal levels. The mean lenticular concentration of calcium was significantly lower in the Group IIIa lenses than that in the Group II lenses and approximated the values observed in the normal control (Group I) lenses. The Group IIIa lenses also exhibited significantly (p<0.05) higher mean lenticular activity of calpain, significantly higher mean mRNA transcript levels of genes that encode m-calpain and lenticular preferred calpain (Lp82), and significantly higher mean levels of the m-calpain and Lp82 proteins than the corresponding values in the Group II lenses. Casein zymography results suggested that chrysin prevented calpain activation and autolysis. Significantly (p<0.05) lower mean levels of mRNA transcripts of the genes that encode calcium transporter proteins (plasma membrane Ca(2+)-ATPase-1 and sarco/endoplasmic reticulum Ca(2+)-ATPase-2) and lenticular apoptotic-cascade proteins (early growth response protein-1, caspase-3, caspase-8, and caspase-9) and significantly (p<0.05) lower mean concentrations of the proteins themselves were seen in the Group IIIa rat lenses in comparison to the values noted in the Group II rat lenses. Chrysin appears to prevent selenite-induced cataractogenesis in vitro by maintaining the redox system components at near-normal levels and by preventing the abnormal expression of several lenticular calcium transporters and apoptotic-cascade proteins, thus preventing accumulation of calcium and subsequent calpain activation and lenticular cell death in cultured Wistar rat lenses.

SLO BK Potassium Channels Couple Gap Junctions to Inhibition of Calcium Signaling in Olfactory Neuron Diversification.

PubMed

Alqadah, Amel; Hsieh, Yi-Wen; Schumacher, Jennifer A; Wang, Xiaohong; Merrill, Sean A; Millington, Grethel; Bayne, Brittany; Jorgensen, Erik M; Chuang, Chiou-Fen

2016-01-01

The C. elegans AWC olfactory neuron pair communicates to specify asymmetric subtypes AWCOFF and AWCON in a stochastic manner. Intercellular communication between AWC and other neurons in a transient NSY-5 gap junction network antagonizes voltage-activated calcium channels, UNC-2 (CaV2) and EGL-19 (CaV1), in the AWCON cell, but how calcium signaling is downregulated by NSY-5 is only partly understood. Here, we show that voltage- and calcium-activated SLO BK potassium channels mediate gap junction signaling to inhibit calcium pathways for asymmetric AWC differentiation. Activation of vertebrate SLO-1 channels causes transient membrane hyperpolarization, which makes it an important negative feedback system for calcium entry through voltage-activated calcium channels. Consistent with the physiological roles of SLO-1, our genetic results suggest that slo-1 BK channels act downstream of NSY-5 gap junctions to inhibit calcium channel-mediated signaling in the specification of AWCON. We also show for the first time that slo-2 BK channels are important for AWC asymmetry and act redundantly with slo-1 to inhibit calcium signaling. In addition, nsy-5-dependent asymmetric expression of slo-1 and slo-2 in the AWCON neuron is necessary and sufficient for AWC asymmetry. SLO-1 and SLO-2 localize close to UNC-2 and EGL-19 in AWC, suggesting a role of possible functional coupling between SLO BK channels and voltage-activated calcium channels in AWC asymmetry. Furthermore, slo-1 and slo-2 regulate the localization of synaptic markers, UNC-2 and RAB-3, in AWC neurons to control AWC asymmetry. We also identify the requirement of bkip-1, which encodes a previously identified auxiliary subunit of SLO-1, for slo-1 and slo-2 function in AWC asymmetry. Together, these results provide an unprecedented molecular link between gap junctions and calcium pathways for terminal differentiation of olfactory neurons.

Adolescents born prematurely with isolated grade 2 haemorrhage in the early 1990s face increased risks of learning challenges.

PubMed

Vohr, Betty R; Allan, Walter; Katz, Karol H; Schneider, Karen; Tucker, Richard; Ment, Laura R

2014-10-01

To compare the impact of low-grade haemorrhage on neurocognitive function in 16-year-old adolescents born preterm, by grade of intraventricular haemorrhage, and term controls. We evaluated 338 preterm adolescents (birth weight 600-1250 g) for intelligence, executive function and memory tasks. Eleven had grade 3-4 haemorrhage, 44 had grade 2, 31 had grade 1, and 251 had no haemorrhage. Group comparisons were made with 102 term age-matched controls, and regression models used to identify the risk that low-grade haemorrhage posed for cognitive, executive function and memory deficits. Preterm adolescents with grade 2 haemorrhage had higher deficit rates of verbal intelligence, receptive vocabulary, phonemic fluency, cognitive flexibility and phonological fluency than preterm adolescents with grade 1 or no haemorrhage, compared with term controls. After excluding preterm adolescents with both grade 2 haemorrhage and cystic periventricular leukomalacia, those with isolated grade 2 haemorrhage remained at greater risk of cognitive and executive function deficits than term controls and of cognitive deficits than preterm adolescents with no haemorrhage. Our findings suggest that preterm adolescents born in the early 1990s with isolated grade 2 haemorrhage are at increased risk of learning challenges, including cognitive and executive function deficits. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Calcium Signaling Is Required for Erythroid Enucleation

PubMed Central

Russell, Sarah M.; Humbert, Patrick O.

2016-01-01

Although erythroid enucleation, the property of erythroblasts to expel their nucleus, has been known for 7ore than a century, surprisingly little is known regarding the molecular mechanisms governing this unique developmental process. Here we show that similar to cytokinesis, nuclear extrusion requires intracellular calcium signaling and signal transduction through the calmodulin (CaM) pathway. However, in contrast to cytokinesis we found that orthochromatic erythroblasts require uptake of extracellular calcium to enucleate. Together these functional studies highlight a critical role for calcium signaling in the regulation of erythroid enucleation. PMID:26731108

Mineral deposition in bacteria-filled and bacteria-free calcium bodies in the crustacean Hyloniscus riparius (Isopoda: Oniscidea).

PubMed

Vittori, Miloš; Rozman, Alenka; Grdadolnik, Jože; Novak, Urban; Štrus, Jasna

2013-01-01

Crustacean calcium bodies are epithelial sacs which contain a mineralized matrix. The objectives of this study were to describe the microscopic anatomy of calcium bodies in the terrestrial isopod Hyloniscus riparius and to establish whether they undergo molt-related structural changes. We performed 3D reconstruction of the calcium bodies from paraffin sections and analyzed their structure with light and electron microscopy. In addition, we analyzed the chemical composition of their mineralized matrices with micro-Raman spectroscopy. Two pairs of these organs are present in H. riparius. One pair is filled with bacteria while the other pair is not. In non-molting animals, the bacteria-filled calcium bodies contain apatite crystals and the bacteria-free calcium bodies enclose CaCO3-containing concretions with little organic matrix. During preparation for molt, an additional matrix layer is deposited in both pairs of calcium bodies. In the bacteria-filled calcium bodies it contains a mixture of calcium carbonate and calcium phosphate, whereas only calcium carbonate is present in bacteria-free calcium bodies. After ecdysis, all mineral components in bacteria-free calcium bodies and the additional matrix layer in bacteria-filled calcium bodies are completely resorbed. During calcium resorption, the apical surface of the calcium body epithelium is deeply folded and electron dense granules are present in spaces between epithelial cells. Our results indicate that the presence of bacteria might be linked to calcium phosphate mineralization. Calcium bodies likely provide a source of calcium and potentially phosphate for the mineralization of the new cuticle after molt. Unlike other terrestrial isopods, H. riparius does not form sternal CaCO3 deposits and the bacteria-free calcium bodies might functionally replace them in this species.

Mineral Deposition in Bacteria-Filled and Bacteria-Free Calcium Bodies in the Crustacean Hyloniscus riparius (Isopoda: Oniscidea)

PubMed Central

Vittori, Miloš; Rozman, Alenka; Grdadolnik, Jože; Novak, Urban; Štrus, Jasna

2013-01-01

Crustacean calcium bodies are epithelial sacs which contain a mineralized matrix. The objectives of this study were to describe the microscopic anatomy of calcium bodies in the terrestrial isopod Hyloniscus riparius and to establish whether they undergo molt-related structural changes. We performed 3D reconstruction of the calcium bodies from paraffin sections and analyzed their structure with light and electron microscopy. In addition, we analyzed the chemical composition of their mineralized matrices with micro-Raman spectroscopy. Two pairs of these organs are present in H. riparius. One pair is filled with bacteria while the other pair is not. In non-molting animals, the bacteria-filled calcium bodies contain apatite crystals and the bacteria-free calcium bodies enclose CaCO3-containing concretions with little organic matrix. During preparation for molt, an additional matrix layer is deposited in both pairs of calcium bodies. In the bacteria-filled calcium bodies it contains a mixture of calcium carbonate and calcium phosphate, whereas only calcium carbonate is present in bacteria-free calcium bodies. After ecdysis, all mineral components in bacteria-free calcium bodies and the additional matrix layer in bacteria-filled calcium bodies are completely resorbed. During calcium resorption, the apical surface of the calcium body epithelium is deeply folded and electron dense granules are present in spaces between epithelial cells. Our results indicate that the presence of bacteria might be linked to calcium phosphate mineralization. Calcium bodies likely provide a source of calcium and potentially phosphate for the mineralization of the new cuticle after molt. Unlike other terrestrial isopods, H. riparius does not form sternal CaCO3 deposits and the bacteria-free calcium bodies might functionally replace them in this species. PMID:23554963

Non-Endoplasmic Reticulum-Based Calr (Calreticulin) Can Coordinate Heterocellular Calcium Signaling and Vascular Function.

PubMed

Biwer, Lauren A; Good, Miranda E; Hong, Kwangseok; Patel, Rahul K; Agrawal, Neha; Looft-Wilson, Robin; Sonkusare, Swapnil K; Isakson, Brant E

2018-01-01

In resistance arteries, endothelial cell (EC) extensions can make contact with smooth muscle cells, forming myoendothelial junction at holes in the internal elastic lamina (HIEL). At these HIEL, calcium signaling is tightly regulated. Because Calr (calreticulin) can buffer ≈50% of endoplasmic reticulum calcium and is expressed throughout IEL holes in small arteries, the only place where myoendothelial junctions form, we investigated the effect of EC-specific Calr deletion on calcium signaling and vascular function. We found Calr expressed in nearly every IEL hole in third-order mesenteric arteries, but not other ER markers. Because of this, we generated an EC-specific, tamoxifen inducible, Calr knockout mouse (EC Calr Δ/Δ). Using this mouse, we tested third-order mesenteric arteries for changes in calcium events at HIEL and vascular reactivity after application of CCh (carbachol) or PE (phenylephrine). We found that arteries from EC Calr Δ/Δ mice stimulated with CCh had unchanged activity of calcium signals and vasodilation; however, the same arteries were unable to increase calcium events at HIEL in response to PE. This resulted in significantly increased vasoconstriction to PE, presumably because of inhibited negative feedback. In line with these observations, the EC Calr Δ/Δ had increased blood pressure. Comparison of ER calcium in arteries and use of an ER-specific GCaMP indicator in vitro revealed no observable difference in ER calcium with Calr knockout. Using selective detergent permeabilization of the artery and inhibition of Calr translocation, we found that the observed Calr at HIEL may not be within the ER. Our data suggest that Calr specifically at HIEL may act in a non-ER dependent manner to regulate arteriolar heterocellular communication and blood pressure. © 2017 American Heart Association, Inc.

Phytoplankton calcification as an effective mechanism to alleviate cellular calcium poisoning

NASA Astrophysics Data System (ADS)

Müller, M. N.; Ramos, J. Barcelos e.; Schulz, K. G.; Riebesell, U.; Kaźmierczak, J.; Gallo, F.; Mackinder, L.; Li, Y.; Nesterenko, P. N.; Trull, T. W.; Hallegraeff, G. M.

2015-11-01

Marine phytoplankton have developed the remarkable ability to tightly regulate the concentration of free calcium ions in the intracellular cytosol at a level of ~ 0.1 μmol L-1 in the presence of seawater Ca2+ concentrations of 10 mmol L-1. The low cytosolic calcium ion concentration is of utmost importance for proper cell signalling function. While the regulatory mechanisms responsible for the tight control of intracellular Ca2+ concentration are not completely understood, phytoplankton taxonomic groups appear to have evolved different strategies, which may affect their ability to cope with changes in seawater Ca2+ concentrations in their environment on geological timescales. For example, the Cretaceous (145 to 66 Ma), an era known for the high abundance of coccolithophores and the production of enormous calcium carbonate deposits, exhibited seawater calcium concentrations up to 4 times present-day levels. We show that calcifying coccolithophore species (Emiliania huxleyi, Gephyrocapsa oceanica and Coccolithus braarudii) are able to maintain their relative fitness (in terms of growth rate and photosynthesis) at simulated Cretaceous seawater calcium concentrations, whereas these rates are severely reduced under these conditions in some non-calcareous phytoplankton species (Chaetoceros sp., Ceratoneis closterium and Heterosigma akashiwo). Most notably, this also applies to a non-calcifying strain of E. huxleyi which displays a calcium sensitivity similar to the non-calcareous species. We hypothesize that the process of calcification in coccolithophores provides an efficient mechanism to alleviate cellular calcium poisoning and thereby offered a potential key evolutionary advantage, responsible for the proliferation of coccolithophores during times of high seawater calcium concentrations. The exact function of calcification and the reason behind the highly ornate physical structures of coccoliths remain elusive.

Selective dopamine receptor 4 activation mediates the hippocampal neuronal calcium response via IP3 and ryanodine receptors.

PubMed

Wang, Ya-Li; Wang, Jian-Gang; Guo, Fang-Li; Gao, Xia-Huan; Zhao, Dan-Dan; Zhang, Lin; Wang, Jian-Zhi; Lu, Cheng-Biao

2017-09-01

Intracellular calcium is a key factor in most cellular processes, including cell growth, differentiation, proliferation and neurotransmitter release. Dopamine (DA) mediates synaptic transmission by regulating the intracellular calcium content. It is not clear, however, which specific subunit of the DA receptor contributes to DA modulation of intracellular calcium content changes. Through the traditional technique of Fura-2 calcium imaging, this study demonstrated that the DA can induce transient calcium in cultured hippocampal neurons and that this response can be mimicked by a selective dopamine receptor 4 (DR4) agonist PD168077 (PD). PD-induced calcium transience can be blocked by a calcium chelator, such as BAPTA-AM, or by pre-treatment of neurons with thapsigargin, a IP 3 receptor antagonist, or a micromolar concentration of ryanodine, a ryanodine receptor (RyR) antagonist. However PD-induced calcium transience cannot be blocked by pre-treatment of neurons with a free-calcium medium or a cocktail of NMDA receptor, L-type calcium channel and alpha7 nicotinic acetylcholine receptor blockers. These results indicate that the calcium response induced by DR4 activation is mainly through activation of IP 3 receptor in internal stores, which is likely to contribute to the DA modulation of synaptic transmission and cognitive function. Copyright © 2017. Published by Elsevier B.V.

Coronary calcium visualization using dual energy chest radiography with sliding organ registration

NASA Astrophysics Data System (ADS)

Wen, Di; Nye, Katelyn; Zhou, Bo; Gilkeson, Robert C.; Wilson, David L.

2016-03-01

Coronary artery calcification (CAC) is the lead biomarker for atherosclerotic heart disease. We are developing a new technique to image CAC using ubiquitously ordered, low cost, low radiation dual energy (DE) chest radiography (using the two-shot GE Revolution XRd system). In this paper, we proposed a novel image processing method (CorCalDx) based on sliding organ registration to create a bone-image-like, coronary calcium image (CCI) that significantly reduces motion artifacts and improves CAC conspicuity. Experiments on images of a physical dynamic cardiac phantom showed that CorCalDx reduced 73% of the motion artifact area as compared to standard DE over a range of heart rates up to 90 bpm and varying x-ray radiation exposures. Residual motion artifact in the phantom CCI is greatly suppressed in gray level and area (0.88% of the heart area). In a Functional Measurement Test (FMT) with 20 clinical exams, image quality improvement of CorCalDx against standard DE (measured from -10 to +10) was significantly suggested (p<0.0001) by three radiologists for cardiac motion artifacts (7.2+/-2.1) and cardiac anatomy visibility (6.1+/-3.5). CorCalDx was always chosen best in every image tested. In preliminary assessments of 12 patients with 18 calcifications, 90% of motion artifact regions in standard DE results were removed in CorCalDx results, with 100% sensitivity of calcification detection, showing great potential of CorCalDx to improve CAC detection and grading in DE chest radiography.

Substrate-dependent changes in mitochondrial function, intracellular free calcium concentration and membrane channels in pancreatic beta-cells.

PubMed

Duchen, M R; Smith, P A; Ashcroft, F M

1993-08-15

Microfluorimetric and patch-clamp techniques have been combined to determine the relationship between changes in mitochondrial metabolism, the activity of KATP channels and changes in intracellular free calcium concentration ([Ca2+]i) in isolated pancreatic beta-cells in response to glucose, ketoisocaproic acid (KIC) and the electron donor couple tetramethyl p-phenylenediamine (TMPD) and ascorbate. Exposure of cells to 20 mM glucose raised NAD(P)H autofluorescence after a delay of 28 +/- 1 s (mean +/- S.E.M., n = 30). The mitochondrial inner membrane potential, delta psi m (monitored using rhodamine 123 fluorescence), hyperpolarized with a latency of 49 +/- 6 s (n = 17), and the [Ca2+]i rose after 129 +/- 13 s (n = 5). The amplitudes of the metabolic changes were graded appropriately with glucose concentration over the range 2.5-20 mM. All variables responded to KIC with shorter latencies: NAD(P)H autofluorescence rose after a delay of 20 +/- 3 s (n = 5) and rhodamine 123 changed after 21 +/- 3 s (n = 6). The electron donor couple, TMPD with ascorbate, rapidly hyperpolarized delta psi m and raised [Ca2+]i. When [Ca2+]i was raised by sustained exposure to 20 mM glucose, TMPD had no further effect. TMPD also decreased whole-cell KATP currents and depolarized the cell membrane, measured with the perforated patch configuration. These data are consistent with a central role for mitochondrial oxidative phosphorylation in coupling changes in glucose concentration with the secretion of insulin.

Intracellular sphingosine releases calcium from lysosomes

PubMed Central

Höglinger, Doris; Haberkant, Per; Aguilera-Romero, Auxiliadora; Riezman, Howard; Porter, Forbes D; Platt, Frances M; Galione, Antony; Schultz, Carsten

2015-01-01

To elucidate new functions of sphingosine (Sph), we demonstrate that the spontaneous elevation of intracellular Sph levels via caged Sph leads to a significant and transient calcium release from acidic stores that is independent of sphingosine 1-phosphate, extracellular and ER calcium levels. This photo-induced Sph-driven calcium release requires the two-pore channel 1 (TPC1) residing on endosomes and lysosomes. Further, uncaging of Sph leads to the translocation of the autophagy-relevant transcription factor EB (TFEB) to the nucleus specifically after lysosomal calcium release. We confirm that Sph accumulates in late endosomes and lysosomes of cells derived from Niemann-Pick disease type C (NPC) patients and demonstrate a greatly reduced calcium release upon Sph uncaging. We conclude that sphingosine is a positive regulator of calcium release from acidic stores and that understanding the interplay between Sph homeostasis, calcium signaling and autophagy will be crucial in developing new therapies for lipid storage disorders such as NPC. DOI: http://dx.doi.org/10.7554/eLife.10616.001 PMID:26613410

A Low Affinity GCaMP3 Variant (GCaMPer) for Imaging the Endoplasmic Reticulum Calcium Store.

PubMed

Henderson, Mark J; Baldwin, Heather A; Werley, Christopher A; Boccardo, Stefano; Whitaker, Leslie R; Yan, Xiaokang; Holt, Graham T; Schreiter, Eric R; Looger, Loren L; Cohen, Adam E; Kim, Douglas S; Harvey, Brandon K

2015-01-01

Endoplasmic reticulum calcium homeostasis is critical for cellular functions and is disrupted in diverse pathologies including neurodegeneration and cardiovascular disease. Owing to the high concentration of calcium within the ER, studying this subcellular compartment requires tools that are optimized for these conditions. To develop a single-fluorophore genetically encoded calcium indicator for this organelle, we targeted a low affinity variant of GCaMP3 to the ER lumen (GCaMPer (10.19)). A set of viral vectors was constructed to express GCaMPer in human neuroblastoma cells, rat primary cortical neurons, and human induced pluripotent stem cell-derived cardiomyocytes. We observed dynamic changes in GCaMPer (10.19) fluorescence in response to pharmacologic manipulations of the ER calcium store. Additionally, periodic calcium efflux from the ER was observed during spontaneous beating of cardiomyocytes. GCaMPer (10.19) has utility in imaging ER calcium in living cells and providing insight into luminal calcium dynamics under physiologic and pathologic states.

The Mitochondrial Calcium Uniporter: Mice can live and die without it

PubMed Central

Harrington, Josephine L; Murphy, Elizabeth

2014-01-01

Calcium is of critical importance to mitochondrial and cell function, and calcium signaling is highly localized in the cell. When stimulated, mitochondria are capable of rapidly taking up calcium, affecting both matrix energetics within mitochondria and shaping the amplitude and frequency of cytosolic calcium “waves”. During pathological conditions a large increase in mitochondrial calcium levels is thought to activate the mitochondrial permeability transition pore, resulting in cell death. The protein responsible for mitochondrial calcium uptake, the mitochondrial calcium uniporter (MCU), was identified in 2011 and its molecular elucidation has stimulated and invigorated research in this area. MCU knockout mice have been created, a variety of other regulators have been identified, and a disease phenotype in humans has been attributed to the loss of a uniporter regulator. In the three years since its molecular elucidation, further research into the MCU has revealed a complex uniporter, and raised many questions about its physiologic and pathologic cell roles. PMID:25451167

The Volumetric Rate of Calcium-rich Transients in the Local Universe

NASA Astrophysics Data System (ADS)

Frohmaier, Chris; Sullivan, Mark; Maguire, Kate; Nugent, Peter

2018-05-01

We present a measurement of the volumetric rate of “calcium-rich” optical transients in the local universe, using a sample of three events from the Palomar Transient Factory (PTF). This measurement builds on a detailed study of the PTF transient detection efficiencies and uses a Monte Carlo simulation of the PTF survey. We measure the volumetric rate of calcium-rich transients to be higher than previous estimates: {1.21}-0.39+1.13 × {10}-5 events yr‑1 Mpc‑3. This is equivalent to 33%–94% of the local volumetric Type Ia supernova rate. This calcium-rich transient rate is sufficient to reproduce the observed calcium abundances in galaxy clusters, assuming an asymptotic calcium yield per calcium-rich event of ∼0.05 {M}ȯ . We also study the PTF detection efficiency of these transients as a function of position within their candidate host galaxies. We confirm as a real physical effect previous results that suggest that calcium-rich transients prefer large physical offsets from their host galaxies.

Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis

NASA Technical Reports Server (NTRS)

Beers, D. R.; Ho, B. K.; Siklos, L.; Alexianu, M. E.; Mosier, D. R.; Mohamed, A. H.; Otsuka, Y.; Kozovska, M. E.; McAlhany, R. E.; Smith, R. G.;

Enamel-like apatite crown covering amorphous mineral in a crayfish mandible

PubMed Central

Bentov, Shmuel; Zaslansky, Paul; Al-Sawalmih, Ali; Masic, Admir; Fratzl, Peter; Sagi, Amir; Berman, Amir; Aichmayer, Barbara

2012-01-01

Carbonated hydroxyapatite is the mineral found in vertebrate bones and teeth, whereas invertebrates utilize calcium carbonate in their mineralized organs. In particular, stable amorphous calcium carbonate is found in many crustaceans. Here we report on an unusual, crystalline enamel-like apatite layer found in the mandibles of the arthropod Cherax quadricarinatus (freshwater crayfish). Despite their very different thermodynamic stabilities, amorphous calcium carbonate, amorphous calcium phosphate, calcite and fluorapatite coexist in well-defined functional layers in close proximity within the mandible. The softer amorphous minerals are found primarily in the bulk of the mandible whereas apatite, the harder and less soluble mineral, forms a wear-resistant, enamel-like coating of the molar tooth. Our findings suggest a unique case of convergent evolution, where similar functional challenges of mastication led to independent developments of structurally and mechanically similar, apatite-based layers in the teeth of genetically remote phyla: vertebrates and crustaceans. PMID:22588301

Structure and function of matrix proteins and peptides in the biomineral formation in crustaceans.

PubMed

Nagasawa, Hiromichi

2011-01-01

Crustaceans have hard cuticle with layered structure, which is composed mainly of chitin, proteins, and calcium carbonate. Crustaceans grow by shedding the old cuticle and replacing it with a new one. Decalcification in the cuticle during the pre-molt stage and concomitant calcification in the stomach to form gastroliths observed in some crustacean species are triggered by the molting hormone. Various proteins and peptides have been identified from calcified cuticle and gastroliths, and their functions have been examined in terms of calcification and interaction with chitin. Acidic nature of matrix proteins is important for recruitment of calcium ions and interaction with calcium carbonate. Examination of the relationship between amino acid sequence containing acidic amino acid residues and calcification inhibitory activity revealed that the potency did not depend on the sequence but on the number of acidic amino acid residues. Calcium carbonate in the calcified tissues of crustaceans is amorphous in many cases. Crustaceans take a strategy to induce and maintain amorphous calcium carbonate by using low-molecular-weight phosphorus compounds.

Hypothyrodism as a risk factor of periodontitis and its relation with vitamin D deficiency: mini-review of literature and a case report.

PubMed

Yussif, Nermin M; El-Mahdi, Fatema Mohammed; Wagih, Rasha

2017-01-01

The purpose of this report is to investigate the role and efficiency of the intra-ligamentary injection of vitamin D and calcium in the treatment of chronic periodontitis associated with hypothyroidism. A 43-year-old female with suspected hypothyroidism who revealed severe chronic periodontitis with grade III mobility. Pre-operative periodontal and systemic control preceded the used intervention. After 3 months, intra-ligamentary injectable vitamin D with calcium was introduced. Clinical evaluation revealed great improvement of the injected sites. Marked reduction of mobility, pocket depth and bleeding were detected. Injectabe vitamin D is an adjunctive treatment modality that needs to be discovered in another way. It may provide further solutions for the periodontal regeneration problem. Clinical studies with large sample sizes and long term follow up are needed.

International Union of Basic and Clinical Pharmacology. C. Nomenclature and Properties of Calcium-Activated and Sodium-Activated Potassium Channels.

PubMed

Kaczmarek, Leonard K; Aldrich, Richard W; Chandy, K George; Grissmer, Stephan; Wei, Aguan D; Wulff, Heike

2017-01-01

A subset of potassium channels is regulated primarily by changes in the cytoplasmic concentration of ions, including calcium, sodium, chloride, and protons. The eight members of this subfamily were originally all designated as calcium-activated channels. More recent studies have clarified the gating mechanisms for these channels and have documented that not all members are sensitive to calcium. This article describes the molecular relationships between these channels and provides an introduction to their functional properties. It also introduces a new nomenclature that differentiates between calcium- and sodium-activated potassium channels. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

One-Dimensional and Two-Dimensional Analytical Solutions for Functionally Graded Beams with Different Moduli in Tension and Compression

PubMed Central

Li, Xue; Dong, Jiao

2018-01-01

The material considered in this study not only has a functionally graded characteristic but also exhibits different tensile and compressive moduli of elasticity. One-dimensional and two-dimensional mechanical models for a functionally graded beam with a bimodular effect were established first. By taking the grade function as an exponential expression, the analytical solutions of a bimodular functionally graded beam under pure bending and lateral-force bending were obtained. The regression from a two-dimensional solution to a one-dimensional solution is verified. The physical quantities in a bimodular functionally graded beam are compared with their counterparts in a classical problem and a functionally graded beam without a bimodular effect. The validity of the plane section assumption under pure bending and lateral-force bending is analyzed. Three typical cases that the tensile modulus is greater than, equal to, or less than the compressive modulus are discussed. The result indicates that due to the introduction of the bimodular functionally graded effect of the materials, the maximum tensile and compressive bending stresses may not take place at the bottom and top of the beam. The real location at which the maximum bending stress takes place is determined via the extreme condition for the analytical solution. PMID:29772835

Mechanically induced intercellular calcium communication in confined endothelial structures.

PubMed

Junkin, Michael; Lu, Yi; Long, Juexuan; Deymier, Pierre A; Hoying, James B; Wong, Pak Kin

2013-03-01

Calcium signaling in the diverse vascular structures is regulated by a wide range of mechanical and biochemical factors to maintain essential physiological functions of the vasculature. To properly transmit information, the intercellular calcium communication mechanism must be robust against various conditions in the cellular microenvironment. Using plasma lithography geometric confinement, we investigate mechanically induced calcium wave propagation in networks of human umbilical vein endothelial cells organized. Endothelial cell networks with confined architectures were stimulated at the single cell level, including using capacitive force probes. Calcium wave propagation in the network was observed using fluorescence calcium imaging. We show that mechanically induced calcium signaling in the endothelial networks is dynamically regulated against a wide range of probing forces and repeated stimulations. The calcium wave is able to propagate consistently in various dimensions from monolayers to individual cell chains, and in different topologies from linear patterns to cell junctions. Our results reveal that calcium signaling provides a robust mechanism for cell-cell communication in networks of endothelial cells despite the diversity of the microenvironmental inputs and complexity of vascular structures. Copyright © 2012 Elsevier Ltd. All rights reserved.

Inhibitory effect of calcium on non-heme iron absorption may be related to translocation of DMT-1 at the apical membrane of enterocytes.

PubMed

Thompson, Ben A V; Sharp, Paul A; Elliott, Ruan; Fairweather-Tait, Susan J

2010-07-28

Many studies show that calcium reduces iron absorption from single meals, but the underlying mechanism is not known. We tested the hypothesis that calcium alters the expression and/or functionality of iron transport proteins. Differentiated Caco-2 cells were treated with ferric ammonium citrate and calcium chloride, and ferritin, DMT-1, and ferroportin were quantified in whole-cell lysate and cell-membrane fractions. Calcium attenuated the iron-induced increase in cell ferritin levels in a dose-dependent manner; a significant decrease was seen at calcium concentrations of 1.25 and 2.5 mM but was only evident after a 16-24 h incubation period. Calcium and iron treatments decreased DMT-1 protein in Caco-2 cell membranes, although total DMT-1 in whole cell lysates was unchanged by either iron or calcium. No change was seen in ferroportin expression. Our data suggest that calcium reduces iron bioavailability by decreasing DMT-1 expression at the apical cell membrane, thereby downregulating iron transport into the cell.

Calcium Biofortification: Three Pronged Molecular Approaches for Dissecting Complex Trait of Calcium Nutrition in Finger Millet (Eleusine coracana) for Devising Strategies of Enrichment of Food Crops

PubMed Central

Sharma, Divya; Jamra, Gautam; Singh, Uma M.; Sood, Salej; Kumar, Anil

2017-01-01

Calcium is an essential macronutrient for plants and animals and plays an indispensable role in structure and signaling. Low dietary intake of calcium in humans has been epidemiologically linked to various diseases which can have serious health consequences over time. Major staple food-grains are poor source of calcium, however, finger millet [Eleusine coracana (L.) Gaertn.], an orphan crop has an immense potential as a nutritional security crop due to its exceptionally high calcium content. Understanding the existing genetic variation as well as molecular mechanisms underlying the uptake, transport, accumulation of calcium ions (Ca2+) in grains is of utmost importance for development of calcium bio-fortified crops. In this review, we have discussed molecular mechanisms involved in calcium accumulation and transport thoroughly, emphasized the role of molecular breeding, functional genomics and transgenic approaches to understand the intricate mechanism of calcium nutrition in finger millet. The objective is to provide a comprehensive up to date account of molecular mechanisms regulating calcium nutrition and highlight the significance of bio-fortification through identification of potential candidate genes and regulatory elements from finger millet to alleviate calcium malnutrition. Hence, finger millet could be used as a model system for explaining the mechanism of elevated calcium (Ca2+) accumulation in its grains and could pave way for development of nutraceuticals or designer crops. PMID:28144246

Calcium Biofortification: Three Pronged Molecular Approaches for Dissecting Complex Trait of Calcium Nutrition in Finger Millet (Eleusine coracana) for Devising Strategies of Enrichment of Food Crops.

PubMed

Sharma, Divya; Jamra, Gautam; Singh, Uma M; Sood, Salej; Kumar, Anil

2016-01-01

Calcium is an essential macronutrient for plants and animals and plays an indispensable role in structure and signaling. Low dietary intake of calcium in humans has been epidemiologically linked to various diseases which can have serious health consequences over time. Major staple food-grains are poor source of calcium, however, finger millet [ Eleusine coracana (L.) Gaertn.], an orphan crop has an immense potential as a nutritional security crop due to its exceptionally high calcium content. Understanding the existing genetic variation as well as molecular mechanisms underlying the uptake, transport, accumulation of calcium ions (Ca 2+ ) in grains is of utmost importance for development of calcium bio-fortified crops. In this review, we have discussed molecular mechanisms involved in calcium accumulation and transport thoroughly, emphasized the role of molecular breeding, functional genomics and transgenic approaches to understand the intricate mechanism of calcium nutrition in finger millet. The objective is to provide a comprehensive up to date account of molecular mechanisms regulating calcium nutrition and highlight the significance of bio-fortification through identification of potential candidate genes and regulatory elements from finger millet to alleviate calcium malnutrition. Hence, finger millet could be used as a model system for explaining the mechanism of elevated calcium (Ca 2+ ) accumulation in its grains and could pave way for development of nutraceuticals or designer crops.

ATP release due to Thy-1–integrin binding induces P2X7-mediated calcium entry required for focal adhesion formation

PubMed Central

Henríquez, Mauricio; Herrera-Molina, Rodrigo; Valdivia, Alejandra; Alvarez, Alvaro; Kong, Milene; Muñoz, Nicolás; Eisner, Verónica; Jaimovich, Enrique; Schneider, Pascal; Quest, Andrew F. G.; Leyton, Lisette

2011-01-01

Thy-1, an abundant mammalian glycoprotein, interacts with αvβ3 integrin and syndecan-4 in astrocytes and thus triggers signaling events that involve RhoA and its effector p160ROCK, thereby increasing astrocyte adhesion to the extracellular matrix. The signaling cascade includes calcium-dependent activation of protein kinase Cα upstream of Rho; however, what causes the intracellular calcium transients required to promote adhesion remains unclear. Purinergic P2X7 receptors are important for astrocyte function and form large non-selective cation pores upon binding to their ligand, ATP. Thus, we evaluated whether the intracellular calcium required for Thy-1-induced cell adhesion stems from influx mediated by ATP-activated P2X7 receptors. Results show that adhesion induced by the fusion protein Thy-1-Fc was preceded by both ATP release and sustained intracellular calcium elevation. Elimination of extracellular ATP with Apyrase, chelation of extracellular calcium with EGTA, or inhibition of P2X7 with oxidized ATP, all individually blocked intracellular calcium increase and Thy-1-stimulated adhesion. Moreover, Thy-1 mutated in the integrin-binding site did not trigger ATP release, and silencing of P2X7 with specific siRNA blocked Thy-1-induced adhesion. This study is the first to demonstrate a functional link between αvβ3 integrin and P2X7 receptors, and to reveal an important, hitherto unanticipated, role for P2X7 in calcium-dependent signaling required for Thy-1-stimulated astrocyte adhesion. PMID:21502139

Apoptosis-linked Gene-2 (ALG-2)/Sec31 Interactions Regulate Endoplasmic Reticulum (ER)-to-Golgi Transport

PubMed Central

Helm, Jared R.; Bentley, Marvin; Thorsen, Kevin D.; Wang, Ting; Foltz, Lauren; Oorschot, Viola; Klumperman, Judith; Hay, Jesse C.

2014-01-01

Luminal calcium released from secretory organelles has been suggested to play a regulatory role in vesicle transport at several steps in the secretory pathway; however, its functional roles and effector pathways have not been elucidated. Here we demonstrate for the first time that specific luminal calcium depletion leads to a significant decrease in endoplasmic reticulum (ER)-to-Golgi transport rates in intact cells. Ultrastructural analysis revealed that luminal calcium depletion is accompanied by increased accumulation of intermediate compartment proteins in COPII buds and clusters of unfused COPII vesicles at ER exit sites. Furthermore, we present several lines of evidence suggesting that luminal calcium affected transport at least in part through calcium-dependent interactions between apoptosis-linked gene-2 (ALG-2) and the Sec31A proline-rich region: 1) targeted disruption of ALG-2/Sec31A interactions caused severe defects in ER-to-Golgi transport in intact cells; 2) effects of luminal calcium and ALG-2/Sec31A interactions on transport mutually required each other; and 3) Sec31A function in transport required luminal calcium. Morphological phenotypes of disrupted ALG-2/Sec31A interactions were characterized. We found that ALG-2/Sec31A interactions were not required for the localization of Sec31A to ER exit sites per se but appeared to acutely regulate the stability and trafficking of the cargo receptor p24 and the distribution of the vesicle tether protein p115. These results represent the first outline of a mechanism that connects luminal calcium to specific protein interactions regulating vesicle trafficking machinery. PMID:25006245

The SigmaR1 chaperone drives breast and colorectal cancer cell migration by tuning SK3-dependent Ca2+ homeostasis.

PubMed

Gueguinou, M; Crottès, D; Chantôme, A; Rapetti-Mauss, R; Potier-Cartereau, M; Clarysse, L; Girault, A; Fourbon, Y; Jézéquel, P; Guérin-Charbonnel, C; Fromont, G; Martin, P; Pellissier, B; Schiappa, R; Chamorey, E; Mignen, O; Uguen, A; Borgese, F; Vandier, C; Soriani, O

2017-06-22

The remodeling of calcium homeostasis contributes to the cancer hallmarks and the molecular mechanisms involved in calcium channel regulation in tumors remain to be characterized. Here, we report that SigmaR1, a stress-activated chaperone, is required to increase calcium influx by triggering the coupling between SK3, a Ca 2+ -activated K + channel (KCNN3) and the voltage-independent calcium channel Orai1. We show that SigmaR1 physically binds SK3 in BC cells. Inhibition of SigmaR1 activity, either by molecular silencing or by the use of sigma ligand (igmesine), decreased SK3 current and Ca 2+ entry in breast cancer (BC) and colorectal cancer (CRC) cells. Interestingly, SigmaR1 inhibition diminished SK3 and/or Orai1 levels in lipid nanodomains isolated from BC cells. Analyses of tissue microarray from CRC patients showed higher SigmaR1 expression levels in cancer samples and a correlation with tumor grade. Moreover, the exploration of a cohort of 4937 BC patients indicated that high expression of SigmaR1 and Orai1 channels was significantly correlated to a lower overall survival. As the SK3/Orai1 tandem drives invasive process in CRC and bone metastasis progression in BC, our results may inaugurate innovative therapeutic approaches targeting SigmaR1 to control the remodeling of Ca 2+ homeostasis in epithelial cancers.

Protective effects of efonidipine, a T- and L-type calcium channel blocker, on renal function and arterial stiffness in type 2 diabetic patients with hypertension and nephropathy.

PubMed

Sasaki, Hidehisa; Saiki, Atsuhito; Endo, Kei; Ban, Noriko; Yamaguchi, Takashi; Kawana, Hidetoshi; Nagayama, Daizi; Ohhira, Masahiro; Oyama, Tomokazu; Miyashita, Yoh; Shirai, Kohji

2009-10-01

The three types of calcium channel blocker (CCB), L-, T- and N-type, possess heterogeneous actions on endothelial function and renal microvascular function. In the present study, we evaluated the effects of two CCBs, efonidipine and amlodipine, on renal function and arterial stiffness. Forty type 2 diabetic patients with hypertension and nephropathy receiving angiotensin receptor II blockers were enrolled and randomly divided into two groups: the efonidipine group was administered efonidipine hydrochloride ethanolate 40 mg/day and the amlodipine group was admin-istered amlodipine besilate 5 mg/day for 12 months. Arterial stiffness was evaluated by the cardio-ankle vascular index (CAVI). Changes in blood pressure during the study were almost the same in the two groups. Sig-nificant increases in serum creatinine and urinary albumin and a significant decrease in the esti-mated glomerular filtration rate were observed in the amlodipine group, but not in the efonidipine group. On the other hand, significant decreases in plasma aldosterone, urinary 8-hydroxy-2'-deoxy-guanosine and CAVI were observed after 12 months in the efonidipine group, but not in the amlo-dipine group. These results suggest that efonidipine, which is both a T-type and L-type calcium chan-nel blocker, has more favorable effects on renal function, oxidative stress and arterial stiffness than amlodipine, an L-type calcium channel blocker.

Dispersion relations of elastic waves in one-dimensional piezoelectric/piezomagnetic phononic crystal with functionally graded interlayers.

PubMed

Guo, Xiao; Wei, Peijun; Lan, Man; Li, Li

2016-08-01

The effects of functionally graded interlayers on dispersion relations of elastic waves in a one-dimensional piezoelectric/piezomagnetic phononic crystal are studied in this paper. First, the state transfer equation of the functionally graded interlayer is derived from the motion equation by the reduction of order (from second order to first order). The transfer matrix of the functionally graded interlayer is obtained by solving the state transfer equation with the spatial-varying coefficient. Based on the transfer matrixes of the piezoelectric slab, the piezomagnetic slab and the functionally graded interlayers, the total transfer matrix of a single cell is obtained. Further, the Bloch theorem is used to obtain the resultant dispersion equations of in-plane and anti-plane Bloch waves. The dispersion equations are solved numerically and the numerical results are shown graphically. Five kinds of profiles of functionally graded interlayers between a piezoelectric slab and a piezomagnetic slab are considered. It is shown that the functionally graded interlayers have evident influences on the dispersion curves and the band gaps. Copyright © 2016 Elsevier B.V. All rights reserved.

The effects of vitamin D and calcium supplementation on pancreatic beta cell function, insulin sensitivity and glycemia in adults at high risk for diabetes. The CaDDM Randomized Controlled Trial

USDA-ARS?s Scientific Manuscript database

Suboptimal vitamin D and calcium status has been associated with higher risk of type 2 diabetes in observational studies but evidence from trials is lacking. The objective of this trial was to determine whether vitamin D supplementation, with or without calcium, improves glucose homeostasis in adult...

Comparison of sevelamer and calcium carbonate on endothelial function and inflammation in patients on peritoneal dialysis.

PubMed

Chennasamudram, Sudha P; Noor, Tanjila; Vasylyeva, Tetyana L

2013-06-01

Hyperphosphataemia is a known independent risk factor for cardiovascular mortality. The objective of the study was to compare the effects of two phosphate binders, sevelamer carbonate and calcium carbonate on endothelial function (EF) and inflammation in patients on peritoneal dialysis (PD) with Type 2 diabetes mellitus (T2DM). Fifteen subjects with hyperphosphataemia discontinued all phosphate binders to undergo a two-week washout and were assigned to sevelamer carbonate or calcium carbonate treatments for eight weeks. After a second two-week washout period, subjects crossed over to either of the alternate treatments for another eight weeks. At the beginning and end of each treatment, biomarkers of EF, pro-inflammatory cytokines, serum albumin, calcium, phosphate and lipids were measured. Sevelamer carbonate significantly improved lipid profile compared with calcium carbonate. Amongst the EF and pro-inflammatory biomarkers, sevelamer carbonate decreased serum endothelin-1, plasminogen activator inhibitor-1, C-reactive protein and interleukin-6. Both phosphate binders were effective in decreasing serum phosphate but sevelamer had a positive effect on EF. Treatment with sevelamer carbonate has beneficial effects compared with calcium carbonate in decreasing inflammation and improving EF in patients with T2DM on PD. © 2013 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Analysis of Spontaneous and Nerve-Evoked Calcium Transients in Intact Extraocular Muscles in Vitro

PubMed Central

Feng, Cheng-Yuan; Hennig, Grant W.; Corrigan, Robert D.; Smith, Terence K.; von Bartheld, Christopher S.

2012-01-01

Extraocular muscles (EOMs) have unique calcium handling properties, yet little is known about the dynamics of calcium events underlying ultrafast and tonic contractions in myofibers of intact EOMs. Superior oblique EOMs of juvenile chickens were dissected with their nerve attached, maintained in oxygenated Krebs buffer, and loaded with fluo-4. Spontaneous and nerve stimulation-evoked calcium transients were recorded and, following calcium imaging, some EOMs were double-labeled with rhodamine-conjugated alpha-bungarotoxin (rhBTX) to identify EOM myofiber types. EOMs showed two main types of spontaneous calcium transients, one slow type (calcium waves with 1/2max duration of 2–12 s, velocity of 25–50 μm/s) and two fast “flash-like” types (Type 1, 30–90 ms; Type 2, 90–150 ms 1/2max duration). Single pulse nerve stimulation evoked fast calcium transients identical to the fast (Type 1) calcium transients. Calcium waves were accompanied by a local myofiber contraction that followed the calcium transient wavefront. The magnitude of calcium-wave induced myofiber contraction far exceeded those of movement induced by nerve stimulation and associated fast calcium transients. Tetrodotoxin eliminated nerve-evoked transients, but not spontaneous transients. Alpha-bungarotoxin eliminated both spontaneous and nerve-evoked fast calcium transients, but not calcium waves, and caffeine increased wave activity. Calcium waves were observed in myofibers lacking spontaneous or evoked fast transients, suggestive of multiply-innervated myofibers, and this was confirmed by double-labeling with rhBTX. We propose that the abundant spontaneous calcium transients and calcium waves with localized contractions that do not depend on innervation may contribute to intrinsic generation of tonic functions of EOMs. PMID:22579493

Radical Vernacular: Bacterial Architecture on Mars

NASA Astrophysics Data System (ADS)

Dade-Robertson, M.; Ramirez-Figueroa, C.; Zhang, M.

Our current speculative discourse on the colonisation of other planets tends to consider future buildings through the lens of hitech architecture. However, we suggest that developments in biotechnology will enable types of construction which are beyond even our current science fictions. The paper presents an argument for bioengineered building materials framed by the notion of constructing buildings on Mars. It introduces the concept of biomineralisation and its processes and applications, and focuses on the creation of calcium carbonate by certain strains of bacteria. We will suggest that by utilising this process in conjunction with synthetic biology (where bacteria are engineered to survive and respond to the environment on other planets) a building process emerges where the materials are adaptive and, to some extent, self-constructed in relation to their environments. The paper concludes by speculating about a building process involving the use of bioengineered bacteria to consolidate materials, found on the surface of Mars, to create materials and structures which are functionally graded.

Calcium carbonate in human gallstones and total CO2 in bile.

PubMed Central

Sutor, D J; Wilkie, L I

1978-01-01

Measurement of total CO2 concentrations in bile from patients undergoing cholecystectomy because of gallstones has shown that the presence of calcium carbonate in the stones can be associated with a raised total CO2 concentration in the common duct bile. In bile from functioning and poorly-functioning gallbladders, total CO2 was nearly always related to pH irrespective of stone composition. PMID:631643

Single-column purification of the tag-free, recombinant form of the neuronal calcium sensor protein, hippocalcin expressed in Escherichia coli.

PubMed

Krishnan, Anuradha; Viviano, Jeffrey; Morozov, Yaroslav; Venkataraman, Venkat

2016-07-01

Hippocalcin is a 193 aa protein that is a member of the neuronal calcium sensor protein family, whose functions are regulated by calcium. Mice that lack the function of this protein are compromised in the long term potentiation aspect of memory generation. Recently, mutations in the gene have been linked with dystonia in human. The protein has no intrinsic enzyme activity but is known to bind to variety of target proteins. Very little information is available on how the protein executes its critical role in signaling pathways, except that it is regulated by binding of calcium. Further delineation of its function requires large amounts of pure protein. In this report, we present a single-step purification procedure that yields high quantities of the bacterially expressed, recombinant protein. The procedure may be adapted to purify the protein from inclusion bodies or cytosol in its myristoylated or non-myristoylated forms. MALDI-MS (in source decay) analyses demonstrates that the myristoylation occurs at the glycine residue. The protein is also biologically active as measured through tryptophan fluorescence, mobility shift and guanylate cyclase activity assays. Thus, further analyses of hippocalcin, both structural and functional, need no longer be limited by protein availability. Copyright © 2016 Elsevier Inc. All rights reserved.

Parathyroid-specific interaction of the calcium-sensing receptor and Gaq

PubMed Central

Pi, Min; Chen, Ling; Huang, MinZhao; Luo, Qiang; Quarles, L. Darryl

2009-01-01

The calcium-sensing receptor regulates various parathyroid gland functions, including hormone secretion, gene transcription, and chief cell hyperplasia through Gαq- and Gαi-dependent signaling pathways. To determine the specific function of Gαq in these processes, we generated transgenic mice using the human parathyroid hormone promoter to drive overexpression of a dominant negative Gαqloop minigene to selectively disrupt Gαq function in the parathyroid gland. The Gαqloop mRNA was highly expressed in the parathyroid gland but not in other tissues of these transgenic mice. Gross appearance, body weight, bone mineral density, and survival of the transgenic mice were indistinguishable from those of their wild-type littermates. Adult transgenic mice, however, exhibited an increase in parathyroid hormone mRNA and in its basal serum level as well as in gland size. The response of the parathyroid gland to hypocalcemia was found to be reduced in sensitivity in the transgenic mice when compared to their wild-type controls. Abnormalities of the parathyroid gland function in these transgenic mice were similar to those of heterozygous Gαq+/− and calcium sensing receptor+/− mice. These studies demonstrate the feasibility of selectively targeting the parathyroid gland to investigate signaling mechanisms downstream of the calcium receptor. PMID:18813283

Evaluation of present thermal barrier coatings for potential service in electric utility gas turbines

NASA Technical Reports Server (NTRS)

Bratton, R. J.; Lau, S. K.; Lee, S. Y.

1982-01-01

The resistance of present-day thermal barrier coatings to combustion gases found in electric utility turbines was assessed. The plasma sprayed coatings, both duplex and graded types, were primarily zirconia-based, although a calcium silicate was also evaluated. Both atmospheric burner rig tests and high pressure tests (135 psig) showed that several present-day thermal barrier coatings have a high potential for service in gas turbines burning the relatively clean GT No. 2 fuel. However, coating improvements are needed for use in turbines burning lower grade fuel such as residual oil. The duplex ZrO2.8Y2O3/NiCrA1Y coating was ranked highest and selected for near-term field testing, with Ca2SiO4/NiCrA1Y ranked second. Graded coatings show potential for corrosive turbine operating conditions and warrant further development. The coating degradation mechanisms for each coating system subjected to the various environmental conditions are also described.

Clogging and Cementation Caused by Calcium or Iron Biogrouts

NASA Astrophysics Data System (ADS)

Ivanov, V.; Chu, J.; Naeimi, M.

2012-12-01

Chemical grouts are often used to reduce the hydraulic conductivity of soil for seepage control purposes. However, chemical grouts can be expensive and environmentally unfriendly. Therefore, two new biogrouts were tested for their bioclogging and biocementation properties. The first was calcium-based biogrout, which contained urease-producing bacteria, calcium chloride and urea for the crystallization of calcite due to enzymatic hydrolysis of urea. The second was iron-based biogrout, which consisted of urease-producing bacteria, ferric chelate, and urea for the precipitation of ferric hydroxide and carbonate due to enzymatic hydrolysis of urea. The permeability of sand (P, 10^-5 m/s), treated with calcium-based biogrout, linearly decreased as a function of the content of precipitated calcium (C, % w/w) according to the following equation: P = 5.1 - 4.0 C. Meanwhile, the permeability of sand treated with iron-based biogrout dropped to 2.7x10^-6 m/s at content of precipitated iron (F, % w/w) about 0.35 % w/w , by the equation: P = 5.1 - 14.6 F , and then slowly decreased to 1.4x10^-7 m/s at content of precipitated iron 1.8% w/w by the following equation: P = 0.36 - 0.23F. Both biogrouts have approximately same efficiency in the reduction of permeability of sand to low values. However, the mechanisms of bioclogging are probably different because the reduction of permeability by calcium-based biogrout was described by linear function of precipitated calcium but the reduction of permeability by iron-based biogrout showed two steps of the clogging. Different functions and mechanisms were related probably to the different type of precipitates. The images of biogrouted sand samples show that calcium-based biogrout produced white amorphous or crystallised calcium carbonate, while iron-based biogrout produced gel-like brown precipitate without visible crystals. The unconfined compressive strengths of the sand treated with different biogrouts (Y, kPa) increased by power function of the precipitated metal content (X, % ww-1) according to the following equations: Y = 14.7X^2 -0.72 X for calcium-based biogrout, and Y = 13.6X^2 + 37.0 X for iron-based biogrout. The strength of wet biocemented sand at the content of precipitated metals below 1.5 % w/w was very low and only at the content of precipitated metal above 3% w/w it was increased to 230 - 240 kPa. Therefore, major geotechnical applications of calcium-based and iron-based biogrouts at the contents of the precipitated metal below 1.5% could be bioclogging of the porous soil rather than its strengthening. This bioclogging could be applicable to the sealing the aquaculture or wastewater treatment ponds, construction of the algal biofuel production ponds, landfill sites, as well as for the plugging of the piping in dams, retaining walls, channels or reservoirs in sandy soil.

Effects of Combined Calcium and Vitamin D Supplementation on Insulin Secretion, Insulin Sensitivity and β-Cell Function in Multi-Ethnic Vitamin D-Deficient Adults at Risk for Type 2 Diabetes: A Pilot Randomized, Placebo-Controlled Trial

PubMed Central

Gagnon, Claudia; Daly, Robin M.; Carpentier, André; Lu, Zhong X.; Shore-Lorenti, Catherine; Sikaris, Ken; Jean, Sonia; Ebeling, Peter R.

2014-01-01

Objectives To examine whether combined vitamin D and calcium supplementation improves insulin sensitivity, insulin secretion, β-cell function, inflammation and metabolic markers. Design 6-month randomized, placebo-controlled trial. Participants Ninety-five adults with serum 25-hydroxyvitamin D [25(OH)D] ≤55 nmol/L at risk of type 2 diabetes (with prediabetes or an AUSDRISK score ≥15) were randomized. Analyses included participants who completed the baseline and final visits (treatment n = 35; placebo n = 45). Intervention Daily calcium carbonate (1,200 mg) and cholecalciferol [2,000–6,000 IU to target 25(OH)D >75 nmol/L] or matching placebos for 6 months. Measurements Insulin sensitivity (HOMA2%S, Matsuda index), insulin secretion (insulinogenic index, area under the curve (AUC) for C-peptide) and β-cell function (Matsuda index x AUC for C-peptide) derived from a 75 g 2-h OGTT; anthropometry; blood pressure; lipid profile; hs-CRP; TNF-α; IL-6; adiponectin; total and undercarboxylated osteocalcin. Results Participants were middle-aged adults (mean age 54 years; 69% Europid) at risk of type 2 diabetes (48% with prediabetes). Compliance was >80% for calcium and vitamin D. Mean serum 25(OH)D concentration increased from 48 to 95 nmol/L in the treatment group (91% achieved >75 nmol/L), but remained unchanged in controls. There were no significant changes in insulin sensitivity, insulin secretion and β-cell function, or in inflammatory and metabolic markers between or within the groups, before or after adjustment for potential confounders including waist circumference and season of recruitment. In a post hoc analysis restricted to participants with prediabetes, a significant beneficial effect of vitamin D and calcium supplementation on insulin sensitivity (HOMA%S and Matsuda) was observed. Conclusions Daily vitamin D and calcium supplementation for 6 months may not change OGTT-derived measures of insulin sensitivity, insulin secretion and β-cell function in multi-ethnic adults with low vitamin D status at risk of type 2 diabetes. However, in participants with prediabetes, supplementation with vitamin D and calcium may improve insulin sensitivity. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12609000043235 PMID:25299668

Differential Item Functioning by Gender on a Large-Scale Science Performance Assessment: A Comparison across Grade Levels.

ERIC Educational Resources Information Center

Holweger, Nancy; Taylor, Grace

The fifth-grade and eighth-grade science items on a state performance assessment were compared for differential item functioning (DIF) due to gender. The grade 5 sample consisted of 8,539 females and 8,029 males and the grade 8 sample consisted of 7,477 females and 7,891 males. A total of 30 fifth grade items and 26 eighth grade items were…

Calcium Sensing by Recoverin: Effect of Protein Conformation on Ion Affinity.

PubMed

Timr, Štěpán; Kadlec, Jan; Srb, Pavel; Ollila, O H Samuli; Jungwirth, Pavel

2018-04-05

The detailed functional mechanism of recoverin, which acts as a myristoyl switch at the rod outer-segment disk membrane, is elucidated by direct and replica-exchange molecular dynamics. In accord with NMR structural evidence and calcium binding assays, simulations point to the key role of enhanced calcium binding to the EF3 loop of the semiopen state of recoverin as compared to the closed state. This 2-4-order decrease in calcium dissociation constant stabilizes the semiopen state in response to the increase of cytosolic calcium concentration in the vicinity of recoverin. A second calcium ion then binds to the EF2 loop and, consequently, the structure of the protein changes from the semiopen to the open state. The latter has the myristoyl chain extruded to the cytosol, ready to act as a membrane anchor of recoverin.

Insights into the activation mechanism of calcium ions on the sericite surface: A combined experimental and computational study

NASA Astrophysics Data System (ADS)

Hu, Yuehua; He, Jianyong; Zhang, Chenhu; Zhang, Chenyang; Sun, Wei; Zhao, Dongbo; Chen, Pan; Han, Haisheng; Gao, Zhiyong; Liu, Runqing; Wang, Li

2018-01-01

The adsorption behaviors and the activation mechanism of calcium ions (Ca2+) on sericite surface have been investigated by Zeta potential measurements, Fourier transform infrared spectroscopy (FT-IR), Micro-flotation tests and First principle calculations. Zeta potential tests results show that the sericite surface potential increases due to the adsorption of calcium ions on the surface. Micro-flotation tests demonstrate that sericite recovery remarkably rise by 10% due to the calcium ions activation on sericite surface. However, the characteristic adsorption bands of calcium oleate do not appear in the FT-IR spectrum, suggesting that oleate ions just physically adsorb on the sericite surface. The first principle calculations based on the density functional theory (DFT) further reveals the microscopic adsorption mechanism of calcium ions on the sericite surface before and after hydration.

Novel calcium-sensing receptor cytoplasmic tail deletion mutation causing autosomal dominant hypocalcemia: molecular and clinical study.

PubMed

Obermannova, Barbora; Sumnik, Zdenek; Dusatkova, Petra; Cinek, Ondrej; Grant, Michael; Lebl, Jan; Hendy, Geoffrey N

2016-04-01

Autosomal dominant hypocalcemia (ADH) is a rare disorder caused by activating mutations of the calcium-sensing receptor (CASR). The treatment of ADH patients with 1α-hydroxylated vitamin D derivatives can cause hypercalciuria leading to nephrocalcinosis. We studied a girl who presented with hypoparathyroidism and asymptomatic hypocalcemia at age 2.5 years. Mutations of CASR were investigated by DNA sequencing. Functional analyses of mutant and WT CASRs were done in transiently transfected human embryonic kidney (HEK293) cells. The proband and her father are heterozygous for an eight-nucleotide deletion c.2703_2710delCCTTGGAG in the CASR encoding the intracellular domain of the protein. Transient expression of CASR constructs in kidney cells in vitro suggested greater cell surface expression of the mutant receptor with a left-shifted extracellular calcium dose-response curve relative to that of the WT receptor consistent with gain of function. Initial treatment of the patient with calcitriol led to increased urinary calcium excretion. Evaluation for mosaicism in the paternal grandparents of the proband was negative. We describe a novel naturally occurring deletion mutation within the CASR that apparently arose de novo in the father of the ADH proband. Functional analysis suggests that the cytoplasmic tail of the CASR contains determinants that regulate the attenuation of signal transduction. Early molecular analysis of the CASR gene in patients with isolated idiopathic hypoparathyroidism is recommended because of its relevance to clinical outcome and treatment choice. In ADH patients, calcium supplementation and low-dose cholecalciferol avoids hypocalcemic symptoms without compromising renal function. © 2016 European Society of Endocrinology.

Vitamin D: the light side of sunshine.

PubMed

Mason, R S; Sequeira, V B; Gordon-Thomson, C

2011-09-01

Under normal circumstances, vitamin D is mainly obtained from skin through the action of ultraviolet B irradiation on 7-dehydrocholesterol. It is further metabolized to 25-hydroxyvitamin D (25OHD), the major circulating vitamin D compound, and then to 1,25-dihydroxyvitamin D, the hormonal form. The major function of vitamin D compounds is to enhance active absorption of ingested calcium (and phosphate). This assists in building bone at younger ages and ensures that despite obligatory urinary losses, bone does not need to be resorbed to maintain blood calcium concentrations. Vitamin D compounds appear to have direct effects to improve bone and muscle function, and there is good, although not entirely consistent, evidence that supplemental vitamin D and calcium together reduce falls and fractures in older individuals. On the basis of calcium control and musculoskeletal function, target levels for 25OHD in blood are at least 50-60 nmol/l and there may be a case for higher targets of 75-80 nmol/l. There are vitamin D receptors in most nucleated cells and some evidence, although not consistent, that adequate vitamin D levels may be important in reducing the incidence of, or mortality from, some cancers and in reducing autoimmune disease. Adequate vitamin D may also allow for a normal innate immune response to pathogens, improve cardiovascular function and mortality and increase insulin responsiveness. Vitamin D levels are maintained better in the presence of adequate calcium intakes, more exercise and less obesity. Genetic variation may have an effect on vitamin D blood levels and response to treatment with vitamin D.

RAPAMYCIN INCREASES LENGTH AND MECHANOSENSORY FUNCTION OF PRIMARY CILIA IN RENAL EPITHELIAL AND VASCULAR ENDOTHELIAL CELLS.

PubMed

Sherpa, Rinzhin T; Atkinson, Kimberly F; Ferreira, Viviana P; Nauli, Surya M

2016-12-01

Primary cilia arebiophysically-sensitive organelles responsible for sensing fluid-flow and transducing this stimulus into intracellular responses. Previous studies have shown that the primary cilia mediate flow-induced calcium influx, and sensitivity of cilia function to flow is correlated to cilia length. Cells with abnormal cilia length or function can lead to a host of diseases that are collectively termed as ciliopathies. Rapamycin, a potent inhibitor of mTOR (mammalian target of rapamycin), has been demonstrated to be a potential pharmacological agent against the aberrant mTOR signaling seen in ciliopathies such as polycystic kidney disease (PKD) and tuberous sclerosis complex (TSC). Here we look at the effects of rapamycin on ciliary length and function for the first time. Compared to controls, primary cilia in rapamycin-treated porcine renal epithelial and mouse vascular endothelial cells showed a significant increase in length. Graded increases in fluid-shear stress further indicates that rapamycin enhances cilia sensitivity to fluid flow. Treatment with rapamycin led to G0 arrest in porcine epithelial cells while no significant change in cell cycle were observed in rapamycin-treated mouse epithelial or endothelial cells, indicating a species-specific effect of rapamycin. Given the previousin vitro and in vivo studies establishing rapamycin as a potential therapeutic agent for ciliopathies, such as PKD and TSC, our studies show that rapamycin enhances ciliary function and sensitivity to fluid flow. The results of our studies suggest a potential ciliotherapeutic effect of rapamycin.

An Asian viewpoint on the use of vitamin D and calcium in osteoporosis treatment: Physician and patient attitudes and beliefs

PubMed Central

2010-01-01

Background Osteoporosis treatment guidelines recommend calcium and vitamin D supplementation for both prevention as well as treatment, however, compliance with these guidelines is often unsatisfactory. This study investigated the opinion of Asian physicians and Asian patients regarding vitamin D and calcium and patients' use of both. Methods Physicians selected from Malaysia, Taiwan, Philippines, Korea and Singapore were asked to grade the significance of vitamin D and calcium in the treatment of osteoporosis and their patients' use of these supplements. In addition, physicians recruited seven eligible osteoporotic women to answer a questionnaire to determine their use of vitamin D and calcium, and their attitudes and beliefs regarding these supplements. Results In total, 237 physicians and 1463 osteoporosis patients completed the questionnaire. The results revealed that 22% of physicians in Malaysia, 12% in Taiwan, 72% in the Philippines, 50% in Korea and 24% in Singapore rated the importance of vitamin D supplementation as being extremely important. For calcium, 27% of physicians in Malaysia, 30% in Taiwan, 80% in the Philippines, 50% in Korea and 38% in Singapore rated the importance as being extremely important. Forty-three percent of patients in Malaysia, 38% in Taiwan, 73% in the Philippines, 35% in Korea and 39% in Singapore rated the importance of vitamin D as being extremely important. For calcium, 69% of patients in Malaysia, 58% in Taiwan, 90% in the Philippines, 70% in Korea and 55% in Singapore rated the importance as being extremely important. In addition, results of the patient questionnaire revealed that only a very small number regularly took both supplements. In addition, the results indicated that, with the exception of patients from the Philippines, the majority of patients had no or infrequent discussion with their physician about vitamin D and calcium. Conclusions There is generally suboptimal appreciation by both physicians and patients of the importance of vitamin D and calcium for maintenance of bone health as reflected in the low number of patients who reported regularly taking these supplements. Recognition of this problem should translate to appropriate action to improve education for both physicians and patients, with a goal to increase use of these supplements among Asian patients with osteoporosis. PMID:20977729

Dietary calcium deficiency in laying ducks impairs eggshell quality by suppressing shell biomineralization.

PubMed

Chen, Wei; Zhao, Fei; Tian, Zhi Mei; Zhang, Han Xing; Ruan, Dong; Li, Yan; Wang, Shuang; Zheng, Chun Tian; Lin, Ying Cai

2015-10-01

The objective of this study was to determine the effects of dietary calcium deficiency on the process of shell formation. Four hundred and fifty female ducks (Anas platyrhynchos) at 22 weeks were randomly assigned to three groups. Ducks were fed one of two calcium-deficient diets (containing 1.8% or 0.38% calcium, respectively) or a calcium-adequate control diet (containing 3.6% calcium) for 67 days (depletion period) and then all ducks were fed a calcium-adequate diet for an additional 67 days (repletion period). Compared with the calcium-adequate control, the average shell thickness, egg shell weight, breaking strength, mammillae density and mammillary knob thickness of shell from ducks that consumed the diet with 0.38% calcium were significantly decreased (P<0.05) during the depletion period, accompanied by reduced tibia quality. The mRNA expression of both secreted phosphoprotein 1 (SPP1) and carbonic anhydrase 2 (CA2) in the uterus was decreased after feeding calcium-deficient diets (1.8% or 0.38% calcium). mRNA transcripts of calbindin 1 (CALB1), an important protein responsible for calcium transport, and the matrix protein genes ovocalyxin-32 (OCX-32) and ovocleidin-116 (OC-116) were reduced in ducks fed 0.38% calcium but not 1.8% calcium. Plasma estradiol concentration was decreased by both of the calcium-deficient diets (P<0.05). The impaired shell quality and suppressed functional proteins involved in shell formation could be reversed by repletion of dietary calcium. The results of the present study suggest that dietary calcium deficiency negatively affects eggshell quality and microarchitecture, probably by suppressing shell biomineralization. © 2015. Published by The Company of Biologists Ltd.

Calcium and ER stress mediate hepatic apoptosis after burn injury

PubMed Central

Gauglitz, Gerd G.; Song, Juquan; Kulp, Gabriela A.; Finnerty, Celeste C.; Cox, Robert A.; Barral, José M.; Herndon, David N.; Boehning, Darren

2009-01-01

Abstract A hallmark of the disease state following severe burn injury is decreased liver function, which results in gross metabolic derangements that compromise patient survival. The underlying mechanisms leading to hepatocyte dysfunction after burn are essentially unknown. The aim of the present study was to determine the underlying mechanisms leading to hepatocyte dysfunction and apoptosis after burn. Rats were randomized to either control (no burn) or burn (60% total body surface area burn) and sacrificed at various time‐points. Liver was either perfused to isolate primary rat hepatocytes, which were used for in vitro calcium imaging, or liver was harvested and processed for immunohistology, transmission electron microscopy, mitochondrial isolation, mass spectroscopy or Western blotting to determine the hepatic response to burn injury in vivo. We found that thermal injury leads to severely depleted endoplasmic reticulum (ER) calcium stores and consequent elevated cytosolic calcium concentrations in primary hepatocytes in vitro. Burn‐induced ER calcium depletion caused depressed hepatocyte responsiveness to signalling molecules that regulate hepatic homeostasis, such as vasopressin and the purinergic agonist ATP. In vivo, thermal injury resulted in activation of the ER stress response and major alterations in mitochondrial structure and function – effects which may be mediated by increased calcium release by inositol 1,4,5‐trisphosphate receptors. Our results reveal that thermal injury leads to dramatic hepatic disturbances in calcium homeostasis and resultant ER stress leading to mitochondrial abnormalities contributing to hepatic dysfunction and apoptosis after burn injury. PMID:20141609

Aberrant Subcellular Neuronal Calcium Regulation in Aging and Alzheimer’s Disease

PubMed Central

Camandola, Simonetta; Mattson, Mark P.

2010-01-01

In this mini-review/opinion article we describe evidence that multiple cellular and molecular alterations in Alzheimer’s disease (AD) pathogenesis involve perturbed cellular calcium regulation, and that alterations in synaptic calcium handling may be early and pivotal events in the disease process. With advancing age neurons encounter increased oxidative stress and impaired energy metabolism, which compromise the function of proteins that control membrane excitability and subcellular calcium dynamics. Altered proteolytic cleavage of the β-amyloid precursor protein (APP) in response to the aging process in combination with genetic and environmental factors results in the production and accumulation of neurotoxic forms of amyloid β-peptide (Aβ ). Aβ undergoes a self-aggregation process and concomitantly generates reactive oxygen species that can trigger membrane-associated oxidative stress which, in turn, impairs the functions of ion-motive ATPases and glutamate and glucose transporters thereby rendering neurons vulnerable to excitotoxicity and apoptosis. Mutations in presenilin-1 that cause early-onset AD increase Aβ production, but also result in an abnormal increase in the size of endoplasmic reticulum calcium stores. Some of the events in the neurodegenerative cascade can be counteracted in animal models by manipulations that stabilize neuronal calcium homeostasis including dietary energy restriction, agonists of glucagon-like peptide 1 receptors and drugs that activate mitochondrial potassium channels. Emerging knowledge of the actions of calcium upstream and downstream of Aβ provides opportunities to develop novel preventative and therapeutic interventions for AD. PMID:20950656

Effects of ultrasound treatment on physico-chemical, functional properties and antioxidant activity of whey protein isolate in the presence of calcium lactate.

PubMed

Jiang, Zhanmei; Yao, Kun; Yuan, Xiangying; Mu, Zhishen; Gao, Zengli; Hou, Juncai; Jiang, Lianzhou

2018-03-01

The aim of this study was to investigate the effects of ultrasound applied at various powers (0, 200, 400, 600 or 800 W) and for different times (20 or 40 min) on the physico-chemical, functional properties and antioxidant activities of whey protein isolate (WPI) dispersions in the presence of 1.20 mmol L -1 calcium lactate. Surface hydrophobicity and free sulfhydryl group of the WPI dispersions containing 1.2 mmol L -1 calcium lactate were significantly enhanced after sonication. Furthermore, particle size of WPI dispersions containing 1.20 mmol L -1 calcium lactate was minimised after sonication. Scanning electron microscopy of sonicated WPI suspensions containing 1.20 mmol L -1 calcium lactate showed that WPI microstructure had significantly changed. After WPI dispersions were treated by sonication assisted with calcium lactate, its gel strength enhanced and solubility decreased. Gel strength of sonicated WPI dispersions (600 W, 40 min) was the maximum among all the WPI treatments. Emulsification activity of sonicated WPI dispersions reduced while its emulsion stability increased. The DPPH radical scavenging activity and ferrous reducing power of sonicated WPI dispersions mostly increased. Ultrasound treatments induced structural changes in WPI molecules, leading to different microstructure and improved gel strength of WPI in the presence of calcium lactate. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Role of acetylcholine receptors in proliferation and differentiation of P19 embryonal carcinoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Resende, R.R.; Alves, A.S.; Britto, L.R.G

2008-04-15

Coordinated proliferation and differentiation of progenitor cells is the base for production of appropriate numbers of neurons and glia during neuronal development in order to establish normal brain functions. We have used murine embryonal carcinoma P19 cells as an in vitro model for early differentiation to study participation of nicotinic (nAChR) and muscarinic acetylcholine (mAChR) receptors in the proliferation of neural progenitor cells and their differentiation to neurons. We have previously shown that functional nicotinic acetylcholine receptors (nAChRs) already expressed in embryonic cells mediate elevations in cytosolic free calcium concentration ([Ca{sup 2+}]{sub i}) via calcium influx through nAChR channels whereasmore » intracellular stores contribute to nAChR- and mAChR-mediated calcium fluxes in differentiated cells [Resende et al., Cell Calcium 43 (2008) 107-121]. In the present study, we have demonstrated that nicotine provoked inhibition of proliferation in embryonic cells as determined by BrdU labeling. However, in neural progenitor cells nicotine stimulated proliferation which was reversed in the presence of inhibitors of calcium mobilization from intracellular stores, indicating that liberation of intracellular calcium contributed to this proliferation induction. Muscarine induced proliferation stimulation in progenitor cells by activation of G{alpha}{sub q/11}-coupled M{sub 1}, M{sub 3} and M{sub 5} receptors and intracellular calcium stores, whereas G{alpha}{sub i/o}-protein coupled M{sub 2} receptor activity mediated neuronal differentiation.« less

TRICHLOROETHYLENE IHIBITS VOLTAGE-SENSITIVE CALCIUM CURRENTS IN DIFFERENTIATED PC 12 CELLS.

EPA Science Inventory

ABSTRACT BODY: It has been demonstrated recently that volatile organic compounds (VOCs)such as toluene, perchloroethylene and trichloroethylene inhibit function of voltage-sensitive calcium channels (VSSC). Such actions are hypothesized to contribute to the acute neurotoxicity of...

A mammalian nervous system-specific plasma membrane proteasome complex that modulates neuronal function

PubMed Central

Ramachandran, Kapil V.; Margolis, Seth S.

2017-01-01

In the nervous system, rapidly occurring processes such as neuronal transmission and calcium signaling are affected by short-term inhibition of proteasome function. It remains unclear how proteasomes can acutely regulate such processes, as this is inconsistent with their canonical role in proteostasis. Here, we made the discovery of a mammalian nervous system-specific membrane proteasome complex that directly and rapidly modulates neuronal function by degrading intracellular proteins into extracellular peptides that can stimulate neuronal signaling. This proteasome complex is tightly associated with neuronal plasma membranes, exposed to the extracellular space, and catalytically active. Selective inhibition of this membrane proteasome complex by a cell-impermeable proteasome inhibitor blocked extracellular peptide production and attenuated neuronal activity-induced calcium signaling. Moreover, membrane proteasome-derived peptides are sufficient to induce neuronal calcium signaling. Our discoveries challenge the prevailing notion that proteasomes primarily function to maintain proteostasis, and highlight a form of neuronal communication through a membrane proteasome complex. PMID:28287632

Calcium bodies of Titanethes albus (Crustacea: Isopoda): molt-related structural dynamics and calcified matrix-associated bacteria.

PubMed

Vittori, Miloš; Kostanjšek, Rok; Znidaršič, Nada; Zagar, Kristina; Ceh, Miran; Strus, Jasna

2012-10-01

Crustaceans form a variety of calcium deposits in which they store calcium necessary for the mineralization of their exoskeletons. Calcium bodies, organs containing large amounts of calcium, have been reported in some terrestrial isopod crustaceans, but have not yet been extensively studied. We analyzed the architecture of these organs during the molt cycle in the isopod Titanethes albus. Two pairs of calcium bodies are positioned ventrolaterally in posterior pereonites of T. albus. Individual organs are epithelial sacs that contain material arranged in concentric layers delimited by thin laminae. As demonstrated by electron microscopy and fluorescence in situ hybridization, abundant bacteria are present within the calcium bodies. Regardless of the molt cycle stage, crystalline concretions are present in the central areas of the calcium bodies. Energy dispersive X-ray spectrometry of the concretions demonstrated that they are composed predominantly of calcium and phosphorus and selected area electron diffraction indicated the presence of hydroxyapatite. In molting animals, a glassy layer of mineralized matrix is formed between the envelope and the outermost lamina of the calcium body. This layer consists of an amorphous calcium mineral which contains less phosphorus than the central concretions and is resorbed after molt. Since changes in the mineralized matrix are synchronized with the molt cycle, the calcium bodies likely function as a storage compartment that complements sternal deposits as a source of calcium for the mineralization of the exoskeleton. Bacteria associated with the mineralized matrix of calcium bodies are evidently involved in calcium dynamics. Copyright © 2012 Elsevier Inc. All rights reserved.

Mechanical and biological properties of the micro-/nano-grain functionally graded hydroxyapatite bioceramics for bone tissue engineering.

PubMed

Zhou, Changchun; Deng, Congying; Chen, Xuening; Zhao, Xiufen; Chen, Ying; Fan, Yujiang; Zhang, Xingdong

2015-08-01

Functionally graded materials (FGM) open the promising approach for bone tissue repair. In this study, a novel functionally graded hydroxyapatite (HA) bioceramic with micrograin and nanograin structure was fabricated. Its mechanical properties were tailored by composition of micrograin and nanograin. The dynamic mechanical analysis (DMA) indicated that the graded HA ceramics had similar mechanical property compared to natural bones. Their cytocompatibility was evaluated via fluorescent microscopy and MTT colorimetric assay. The viability and proliferation of rabbit bone marrow mesenchymal stem cells (BMSCs) on ceramics indicated that this functionally graded HA ceramic had better cytocompatibility than conventional HA ceramic. This study demonstrated that functionally graded HA ceramics create suitable structures to satisfy both the mechanical and biological requirements of bone tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phosphorylation of serine residues is fundamental for the calcium-binding ability of Orchestin, a soluble matrix protein from crustacean calcium storage structures.

PubMed

Hecker, Arnaud; Testenière, Olivier; Marin, Frédéric; Luquet, Gilles

2003-01-30

Orchestia cavimana is a terrestrial crustacean, which cyclically stores calcium in diverticula of the midgut, in the form of calcified amorphous concretions. These concretions are associated with a proteinaceous matrix, the main constituent of the soluble matrix is Orchestin, an acidic calcium-binding protein [Testenière et al., Biochem. J. 361 (2002) 327-335]. In the present paper, we clearly demonstrate that Orchestin is phosphorylated on serine and tyrosine residues, but that calcium binding only occurs via the phosphoserine residues. To our knowledge, this is the first example of an invertebrate mineralization for which a post-translational modification is clearly related to an important function of a calcifying protein.

Augmentation of tibial plateau fractures with an injectable bone substitute: CERAMENT™. Three year follow-up from a prospective study.

PubMed

Iundusi, Riccardo; Gasbarra, Elena; D'Arienzo, Michele; Piccioli, Andrea; Tarantino, Umberto

2015-05-13

Reduction of tibial plateau fractures and maintain a level of well aligned congruent joint is key to a satisfactory clinical outcome and is important for the return to pre-trauma level of activity. Stable internal fixation support early mobility and weight bearing. The augmentation with bone graft substitute is often required to support the fixation to mantain reduction. For these reasons there has been development of novel bone graft substitutes for trauma applications and in particular synthetic materials based on calcium phosphates and/or apatite combined with calcium sulfates. Injectable bone substitutes can optimize the filling of irregular bone defects. The purpose of this study was to assess the potential of a novel injectable bone substitute CERAMENT™|BONE VOID FILLER in supporting the initial reduction and preserving alignment of the joint surface until fracture healing. From June 2010 through May 2011 adult patients presenting with acute, closed and unstable tibial plateau fractures which required both grafting and internal fixation, were included in a prospective study with percutaneous or open reduction and internal fixation (ORIF) augmented with an injectable ceramic biphasic bone substitute CERAMENT™|BONE VOID FILLER (BONESUPPORT™, Lund, Sweden) to fill residual voids. Clinical follow up was performed at 1, 3, 9 and 12 months and any subsequent year; including radiographic analysis and Rasmussen system for knee functional grading. Twenty four patients, balanced male-to-female, with a mean age of 47 years, were included and followed with an average of 44 months (range 41-52 months). Both Schatzker and Müller classifications were used and was type II or 41-B3 in 7 patients, type III or 41-B2 in 12 patients, type IV or 41-C1 in 2 patients and type VI or 41-C3 in 3 patients, respectively. The joint alignement was satisfactory and manteined within a range of 2 mm, with an average of 1.18 mm. The mean Rasmussen knee function score was 26.5, with 14 patients having an excellent result and the remaining 10 with a good result. It can be concluded that radiological and clinical outcome was satisfactory and obtained in all cases without complications. This injectable novel biphasic hydroxyapatite and calcium sulfate ceramic material is a valuable armamentarium in the treatment of trauma where bone graft is required.

Evaluating Sermons: The Function of Grades in Teaching Preaching

ERIC Educational Resources Information Center

Helsel, Carolyn Browning

2017-01-01

What are grades doing in a homiletics classroom? This article traces the function of grades through the broader history of the educational system in the United States and then makes suggestions for how grades can be used more effectively in teaching preaching. Beginning in the nineteenth century, teachers used grades to rank and motivate students,…

Determination of antitrypsin activity on agar plates: relationship between antitrypsin and biological value of soybean for trout.

PubMed

Sandholm, M; Smith, R R; Shih, J C; Scott, M L

1976-06-01

A new method is described for determination of antitrypsin activity based on inhibition of trypsin solubilization of calcium caseinate in agar plates. The method was applied to analyze soybeans after graded heat treatments for their antitrypsin content. Biological determination of protein and energy values of the soybean samples showed direct correlation of these values with the destruction of antitrypsin as measured by the new method, using rainbow trout.

A food-grade process for isolation and partial purification of bacteriocins of lactic acid bacteria that uses diatomite calcium silicate.

PubMed Central

Coventry, M J; Gordon, J B; Alexander, M; Hickey, M W; Wan, J

1996-01-01

Bacteriocins, including nisin, pediocin PO2, brevicin 286, and piscicolin 126, were extracted from fermentation media by adsorption onto Micro-Cel (a food-grade diatomite calcium silicate anticaking agent) and subsequent desorption. The optimal conditions for desorption of piscicolin 126 were determined and applied to other bacteriocins, and the relative purities of the desorbed preparations were compared. Piscicolin was not successfully desorbed from Micro-Cel at pH 1.0 to 12.0, with organic solvents, or by increase of ionic strength up to 1 M NaCl. However, 25 and 75% of the bacteriocin activity was desorbed by using 1% sodium deoxycholate and 1% sodium dodecyl sulfate (SDS), respectively. Higher levels (up to 100%) of desorption were achieved by repeated elution or by an increase in surfactant concentration. Desorption of piscicolin with 1/10 volume of SDS solution resulted in a preparation with 10 times concentration in activity, equivalent to that of ammonium sulfate preparations (409,600 to 819,200 activity units/ml). Determination of organic nitrogen (N) content revealed that the desorbed piscicolin preparations were substantially free of proteinaceous substances (approximately 92 to 99%) compared with original culture supernatants and ammonium sulfate preparations. Nisin, pediocin, and brevicin were also desorbed with 1% SDS with a similar level of purification. PMID:8633875

ALBI versus Child-Pugh grading systems for liver function in patients with hepatocellular carcinoma.

PubMed

Na, Seong K; Yim, Sun Y; Suh, Sang J; Jung, Young K; Kim, Ji H; Seo, Yeon S; Yim, Hyung J; Yeon, Jong E; Byun, Kwan S; Um, Soon H

2018-04-01

The prognostic performance of the albumin-bilirubin (ALBI) grade in hepatocellular carcinoma (HCC) as an objective method of assessing liver function was investigated. Data from 2099 patients with HCC in Korea were collected and analyzed retrospectively. The discriminative performance of ALBI grade was compared with Child-Pugh (C-P) grade for different stages or treatments. The median follow up duration was 16.2 months (range: 1.0-124.9). The median survival times were 49.7 months for C-P grade A (65.8%), 12.4 months for C-P grade B (25.5%), and 4.2 months for C-P grade C (8.6%) (P < 0.001). The median survival times were 84.2 months for ALBI grade 1 (32.8%), 25.5 months for ALBI grade 2 (53.5%), and 7.7 months for ALBI grade 3 (13.7%) (P < 0.001). In early UICC stages, ALBI grade showed better discriminative performance than C-P grade. In curative treatments, ALBI grade also showed better discriminative performance than C-P grade (Harrell's C: 0.624 (C-P grade) vs 0.667 [ALBI grade]). ALBI grade provided better prognostic performance in survival analysis and better distribution of the grades than C-P grade in HCC, suggesting that ALBI grade could be a good alternative grading system for liver function in patients with HCC. © 2018 Wiley Periodicals, Inc.

The Volumetric Rate of Calcium-rich Transients in the Local Universe

DOE PAGES

Frohmaier, Chris; Sullivan, Mark; Maguire, Kate; ...

2018-05-04

Here, we present a measurement of the volumetric rate of "calcium-rich" optical transients in the local universe, using a sample of three events from the Palomar Transient Factory (PTF). This measurement builds on a detailed study of the PTF transient detection efficiencies and uses a Monte Carlo simulation of the PTF survey. We measure the volumetric rate of calcium-rich transients to be higher than previous estimates: 1.21 -0.39 +1.13 10 -5 events yr -1Mpc -3. This is equivalent to 33%-94% of the local volumetric Type Ia supernova rate. This calcium-rich transient rate is sufficient to reproduce the observed calcium abundancesmore » in galaxy clusters, assuming an asymptotic calcium yield per calcium-rich event of ~0.05 M ⊙. As a result, we also study the PTF detection efficiency of these transients as a function of position within their candidate host galaxies. We confirm as a real physical effect previous results that suggest that calcium-rich transients prefer large physical offsets from their host galaxies.« less

Calcium as a signal integrator in developing epithelial tissues.

PubMed

Brodskiy, Pavel A; Zartman, Jeremiah J

2018-05-16

Decoding how tissue properties emerge across multiple spatial and temporal scales from the integration of local signals is a grand challenge in quantitative biology. For example, the collective behavior of epithelial cells is critical for shaping developing embryos. Understanding how epithelial cells interpret a diverse range of local signals to coordinate tissue-level processes requires a systems-level understanding of development. Integration of multiple signaling pathways that specify cell signaling information requires second messengers such as calcium ions. Increasingly, specific roles have been uncovered for calcium signaling throughout development. Calcium signaling regulates many processes including division, migration, death, and differentiation. However, the pleiotropic and ubiquitous nature of calcium signaling implies that many additional functions remain to be discovered. Here we review a selection of recent studies to highlight important insights into how multiple signals are transduced by calcium transients in developing epithelial tissues. Quantitative imaging and computational modeling have provided important insights into how calcium signaling integration occurs. Reverse-engineering the conserved features of signal integration mediated by calcium signaling will enable novel approaches in regenerative medicine and synthetic control of morphogenesis.

Inherent rhythm of smooth muscle cells in rat mesenteric arterioles: An eigensystem formulation

NASA Astrophysics Data System (ADS)

Ho, I. Lin; Moshkforoush, Arash; Hong, Kwangseok; Meininger, Gerald A.; Hill, Michael A.; Tsoukias, Nikolaos M.; Kuo, Watson

2016-04-01

On the basis of experimental data and mathematical equations in the literature, we remodel the ionic dynamics of smooth muscle cells (SMCs) as an eigensystem formulation, which is valid for investigating finite variations of variables from the equilibrium such as in common experimental operations. This algorithm provides an alternate viewpoint from frequency-domain analysis and enables one to probe functionalities of SMCs' rhythm by means of a resonance-related mechanism. Numerical results show three types of calcium oscillations of SMCs in mesenteric arterioles: spontaneous calcium oscillation, agonist-dependent calcium oscillation, and agonist-dependent calcium spike. For simple single and double SMCs, we demonstrate properties of synchronization among complex signals related to calcium oscillations, and show different correlation relations between calcium and voltage signals for various synchronization and resonance conditions. For practical cell clusters, our analyses indicate that the rhythm of SMCs could (1) benefit enhancements of signal communications among remote cells, (2) respond to a significant calcium peaking against transient stimulations for triggering globally oscillating modes, and (3) characterize the globally oscillating modes via frog-leap (non-molecular-diffusion) calcium waves across inhomogeneous SMCs.

Polymeric additives to enhance the functional properties of calcium phosphate cements

PubMed Central

Perez, Roman A; Kim, Hae-Won

2012-01-01

The vast majority of materials used in bone tissue engineering and regenerative medicine are based on calcium phosphates due to their similarity with the mineral phase of natural bone. Among them, calcium phosphate cements, which are composed of a powder and a liquid that are mixed to obtain a moldable paste, are widely used. These calcium phosphate cement pastes can be injected using minimally invasive surgery and adapt to the shape of the defect, resulting in an entangled network of calcium phosphate crystals. Adding an organic phase to the calcium phosphate cement formulation is a very powerful strategy to enhance some of the properties of these materials. Adding some water-soluble biocompatible polymers in the calcium phosphate cement liquid or powder phase improves physicochemical and mechanical properties, such as injectability, cohesion, and toughness. Moreover, adding specific polymers can enhance the biological response and the resorption rate of the material. The goal of this study is to overview the most relevant advances in this field, focusing on the different types of polymers that have been used to enhance specific calcium phosphate cement properties. PMID:22511991

The Volumetric Rate of Calcium-rich Transients in the Local Universe

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frohmaier, Chris; Sullivan, Mark; Maguire, Kate

Here, we present a measurement of the volumetric rate of "calcium-rich" optical transients in the local universe, using a sample of three events from the Palomar Transient Factory (PTF). This measurement builds on a detailed study of the PTF transient detection efficiencies and uses a Monte Carlo simulation of the PTF survey. We measure the volumetric rate of calcium-rich transients to be higher than previous estimates: 1.21 -0.39 +1.13 10 -5 events yr -1Mpc -3. This is equivalent to 33%-94% of the local volumetric Type Ia supernova rate. This calcium-rich transient rate is sufficient to reproduce the observed calcium abundancesmore » in galaxy clusters, assuming an asymptotic calcium yield per calcium-rich event of ~0.05 M ⊙. As a result, we also study the PTF detection efficiency of these transients as a function of position within their candidate host galaxies. We confirm as a real physical effect previous results that suggest that calcium-rich transients prefer large physical offsets from their host galaxies.« less

Distance-dependent gradient in NMDAR-driven spine calcium signals along tapering dendrites

PubMed Central

Walker, Alison S.; Grillo, Federico; Jackson, Rachel E.; Rigby, Mark; Lowe, Andrew S.; Vizcay-Barrena, Gema; Fleck, Roland A.; Burrone, Juan

2017-01-01

Neurons receive a multitude of synaptic inputs along their dendritic arbor, but how this highly heterogeneous population of synaptic compartments is spatially organized remains unclear. By measuring N-methyl-d-aspartic acid receptor (NMDAR)-driven calcium responses in single spines, we provide a spatial map of synaptic calcium signals along dendritic arbors of hippocampal neurons and relate this to measures of synapse structure. We find that quantal NMDAR calcium signals increase in amplitude as they approach a thinning dendritic tip end. Based on a compartmental model of spine calcium dynamics, we propose that this biased distribution in calcium signals is governed by a gradual, distance-dependent decline in spine size, which we visualized using serial block-face scanning electron microscopy. Our data describe a cell-autonomous feature of principal neurons, where tapering dendrites show an inverse distribution of spine size and NMDAR-driven calcium signals along dendritic trees, with important implications for synaptic plasticity rules and spine function. PMID:28209776

Calcium signal communication in the central nervous system.

PubMed

Braet, Katleen; Cabooter, Liesbet; Paemeleire, Koen; Leybaert, Luc

2004-02-01

The communication of calcium signals between cells is known to be operative between neurons where these signals integrate intimately with electrical and chemical signal communication at synapses. Recently, it has become clear that glial cells also exchange calcium signals between each other in cultures and in brain slices. This communication pathway has received utmost attention since it is known that astrocytic calcium signals can be induced by neuronal stimulation and can be communicated back to the neurons to modulate synaptic transmission. In addition to this, cells that are generally not considered as brain cells become progressively incorporated in the picture, as astrocytic calcium signals are reported to be communicated to endothelial cells of the vessel wall and can affect smooth muscle cell tone to influence the vessel diameter and thus blood flow. We review the available evidence for calcium signal communication in the central nervous system, taking into account a basic functional unit -the brain cell tripartite- consisting of neurons, glial cells and vascular cells and with emphasis on glial-vascular calcium signaling aspects.

Calcium-activated butyrylcholinesterase in human skin protects acetylcholinesterase against suicide inhibition by neurotoxic organophosphates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schallreuter, Karin U.; Institute for Pigmentary Disorders in Association with EM Arndt University of Greifswald; University of Bradford

The human epidermis holds an autocrine acetylcholine production and degradation including functioning membrane integrated and cytosolic butyrylcholinesterase (BuchE). Here we show that BuchE activities increase 9-fold in the presence of calcium (0.5 x 10{sup -3}M) via a specific EF-hand calcium binding site, whereas acetylcholinesterase (AchE) is not affected. {sup 45}Calcium labelling and computer simulation confirmed the presence of one EF-hand binding site per subunit which is disrupted by H{sub 2}O{sub 2}-mediated oxidation. Moreover, we confirmed the faster hydrolysis by calcium-activated BuchE using the neurotoxic organophosphate O-ethyl-O-(4-nitrophenyl)-phenylphosphonothioate (EPN). Considering the large size of the human skin with 1.8 m{sup 2} surfacemore » area with its calcium gradient in the 10{sup -3}M range, our results implicate calcium-activated BuchE as a major protective mechanism against suicide inhibition of AchE by organophosphates in this non-neuronal tissue.« less

A deterministic model predicts the properties of stochastic calcium oscillations in airway smooth muscle cells.

PubMed

Cao, Pengxing; Tan, Xiahui; Donovan, Graham; Sanderson, Michael J; Sneyd, James

2014-08-01

The inositol trisphosphate receptor ([Formula: see text]) is one of the most important cellular components responsible for oscillations in the cytoplasmic calcium concentration. Over the past decade, two major questions about the [Formula: see text] have arisen. Firstly, how best should the [Formula: see text] be modeled? In other words, what fundamental properties of the [Formula: see text] allow it to perform its function, and what are their quantitative properties? Secondly, although calcium oscillations are caused by the stochastic opening and closing of small numbers of [Formula: see text], is it possible for a deterministic model to be a reliable predictor of calcium behavior? Here, we answer these two questions, using airway smooth muscle cells (ASMC) as a specific example. Firstly, we show that periodic calcium waves in ASMC, as well as the statistics of calcium puffs in other cell types, can be quantitatively reproduced by a two-state model of the [Formula: see text], and thus the behavior of the [Formula: see text] is essentially determined by its modal structure. The structure within each mode is irrelevant for function. Secondly, we show that, although calcium waves in ASMC are generated by a stochastic mechanism, [Formula: see text] stochasticity is not essential for a qualitative prediction of how oscillation frequency depends on model parameters, and thus deterministic [Formula: see text] models demonstrate the same level of predictive capability as do stochastic models. We conclude that, firstly, calcium dynamics can be accurately modeled using simplified [Formula: see text] models, and, secondly, to obtain qualitative predictions of how oscillation frequency depends on parameters it is sufficient to use a deterministic model.

Metabotropic glutamate receptors activate dendritic calcium waves and TRPM channels which drive rhythmic respiratory patterns in mice

PubMed Central

Mironov, S L

2008-01-01

Respiration in vertebrates is generated by a compact network which is located in the lower brainstem but cellular mechanisms which underlie persistent oscillatory activity of the respiratory network are yet unknown. Using two-photon imaging and patch-clamp recordings in functional brainstem preparations of mice containing pre-Bötzinger complex (preBötC), we examined the actions of metabotropic glutamate receptors (mGluR1/5) on the respiratory patterns. The agonist DHPG potentiated and antagonist LY367385 depressed respiration-related activities. In the inspiratory neurons, we observed rhythmic activation of non-selective channels which had a conductance of 24 pS. Their activity was enhanced with membrane depolarization and after elevation of calcium from the cytoplasmic side of the membrane. They were activated by a non-hydrolysable PIP2 analogue and blocked by flufenamate, ATP4− and Gd3+. All these properties correspond well to those of TRPM4 channels. Calcium imaging of functional slices revealed rhythmic transients in small clusters of neurons present in a network. Calcium transients in the soma were preceded by the waves in dendrites which were dependent on mGluR activation. Initiation and propagation of waves required calcium influx and calcium release from internal stores. Calcium waves activated TPRM4-like channels in the soma and promoted generation of inspiratory bursts. Simulations of activity of neurons communicated via dendritic calcium waves showed emerging activity within neuronal clusters and its synchronization between the clusters. The experimental and theoretical data provide a subcellular basis for a recently proposed group-pacemaker hypothesis and describe a novel mechanism of rhythm generation in neuronal networks. PMID:18308826

Induction of endoplasmic reticulum calcium pump expression during early leukemic B cell differentiation.

PubMed

Aït Ghezali, Lamia; Arbabian, Atousa; Roudot, Hervé; Brouland, Jean-Philippe; Baran-Marszak, Fanny; Salvaris, Evelyn; Boyd, Andrew; Drexler, Hans G; Enyedi, Agnes; Letestu, Remi; Varin-Blank, Nadine; Papp, Bela

2017-06-26

Endoplasmic reticulum (ER) calcium storage and release play important roles in B lymphocyte maturation, survival, antigen-dependent cell activation and immunoglobulin synthesis. Calcium is accumulated in the endoplasmic reticulum (ER) by Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes). Because lymphocyte function is critically dependent on SERCA activity, it is important to understand qualitative and quantitative changes of SERCA protein expression that occur during B lymphoid differentiation and leukemogenesis. In this work we investigated the modulation of SERCA expression during the pharmacologically induced differentiation of leukemic precursor B lymphoblast cell lines that carry the E2A-PBX1 fusion oncoprotein. Changes of SERCA levels during differentiation were determined and compared to those of established early B lymphoid differentiation markers. SERCA expression of the cells was compared to that of mature B cell lines as well, and the effect of the direct inhibition of SERCA-dependent calcium transport on the differentiation process was investigated. We show that E2A-PBX1 + leukemia cells simultaneously express SERCA2 and SERCA3-type calcium pumps; however, their SERCA3 expression is markedly inferior to that of mature B cells. Activation of protein kinase C enzymes by phorbol ester leads to phenotypic differentiation of the cells, and this is accompanied by the induction of SERCA3 expression. Direct pharmacological inhibition of SERCA-dependent calcium transport during phorbol ester treatment interferes with the differentiation process. These data show that the calcium pump composition of the ER is concurrent with increased SERCA3 expression during the differentiation of precursor B acute lymphoblastic leukemia cells, that a cross-talk exists between SERCA function and the control of differentiation, and that SERCA3 may constitute an interesting new marker for the study of early B cell phenotype.

Development of calcium bodies in Hylonsicus riparius (Crustacea: Isopoda).

PubMed

Vittori, Miloš; Khurshed, Mohammed; Picavet, Daisy I; van Noorden, Cornelis J F; Štrus, Jasna

2018-03-01

Calcium bodies are internal epithelial sacs found in terrestrial isopods of the family Trichoniscidae that contain a mineralized extracellular matrix that is deposited and resorbed in relation to the molt cycle. Calcium bodies in several trichoniscids are filled with bacteria, the function of which is currently unknown. The woodlouse Hyloniscus riparius differs from other trichoniscids in that it possesses two different pairs of calcium bodies, the posterior pair being filled with bacteria and the anterior pair being devoid of bacteria. We explored the development of these organs and bacterial colonization of their lumen during the postmarsupial development with the use of optical clearing and whole-body confocal imaging of larval and juvenile stages. Our results show that calcium bodies are formed as invaginations of the epidermis in the region of intersegmental membranes during the postmarsupial development. The anterior pair of calcium bodies is generated during the first postmarsupial manca stage, whereas the posterior calcium bodies first appear in juveniles and are immediately colonized by bacteria, likely through a connection between the calcium body lumen and the body surface. Mineral is deposited in calcium bodies as soon as they are present. Copyright © 2018 Elsevier Ltd. All rights reserved.

Electrophoretic mobility shift in native gels indicates calcium-dependent structural changes of neuronal calcium sensor proteins.

PubMed

Viviano, Jeffrey; Krishnan, Anuradha; Wu, Hao; Venkataraman, Venkat

2016-02-01

In proteins of the neuronal calcium sensor (NCS) family, changes in structure as well as function are brought about by the binding of calcium. In this article, we demonstrate that these structural changes, solely due to calcium binding, can be assessed through electrophoresis in native gels. The results demonstrate that the NCS proteins undergo ligand-dependent conformational changes that are detectable in native gels as a gradual decrease in mobility with increasing calcium but not other tested divalent cations such as magnesium, strontium, and barium. Surprisingly, such a gradual change over the entire tested range is exhibited only by the NCS proteins but not by other tested calcium-binding proteins such as calmodulin and S100B, indicating that the change in mobility may be linked to a unique NCS family feature--the calcium-myristoyl switch. Even within the NCS family, the changes in mobility are characteristic of the protein, indicating that the technique is sensitive to the individual features of the protein. Thus, electrophoretic mobility on native gels provides a simple and elegant method to investigate calcium (small ligand)-induced structural changes at least in the superfamily of NCS proteins. Copyright © 2015 Elsevier Inc. All rights reserved.

Combined use of UV-labile calcium chelators and calcium-sensitive dyes in a microscope with two light sources influencing different regions in a group of coordinated contracting cardiac myocytes

NASA Astrophysics Data System (ADS)

Pilarczyk, Goetz; Greulich, Karl-Otto

1997-12-01

The coordination of excitation in a biological system of cells such as cardiac myocytes in heart tissue has crucial influence on the function of the entire organ. This coordinated behavior can be visualized in a small group of embryonic cardiac myocytes derived from the hearts of unborn chicken. Loaded with a calcium sensitive dye the excitation can be imaged via the occurring transient rise in cytosolic calcium concentration. It can be shown that in regions with physiological or morphological restrictions the transient rise in cytosolic calcium occurs with a temporal delay compared to the ordinary array of coupled myocytes. The height of the transient rise of cytosolic calcium is related to the ability of the individual cell to participate in the coordinated contraction. The free cytosolic calcium concentration is decreased with the UV-labile calcium, chelator diazo-2. Our setup allows to decrease the free cytosolic calcium in a single cell of the contracting array of cells. This allows us to introduce mismatches in selected regions of the coordinated contraction and to visualize the effects simultaneously.

Hawthorn extract inhibits human isolated neutrophil functions.

PubMed

Dalli, Ernesto; Milara, Javier; Cortijo, Julio; Morcillo, Esteban J; Cosín-Sales, Juan; Sotillo, José Francisco

2008-06-01

Hawthorn extract is a popular herbal medicine given as adjunctive treatment for chronic heart failure. In contrast to the cardiac properties of hawthorn extract, its anti-inflammatory effect has been scarcely investigated. This study examines the effects of a dry extract of leaves and flowers of Crataegus laevigata on various functional outputs of human neutrophils in vitro. Incubation of human neutrophils obtained from peripheral blood of healthy donors with C. laevigata extract (0.75-250 microg/ml) inhibited N-formyl-Met-Leu-Phe (FMLP)-induced superoxide anion generation, elastase release and chemotactic migration with potency values of 43.6, 21.9, and 31.6 microg/ml, respectively. By contrast, serum-opsonized zymosan-induced phagocytosis was unaltered by plant extract. C. laevigata extract (125 microg/ml) reduced FMLP-induced leukotriene B(4) production and lipopolysaccharide-induced generation of tumour necrosis factor-alpha and interleukin-8. Extract inhibited FMLP-induced intracellular calcium signal with potency of 17.4 microg/ml. Extract also markedly inhibited the extracellular calcium entry into calcium-depleted neutrophils, and the thapsigargin-induced intracellular calcium response. In conclusion, C. laevigata extract inhibited various functional outputs of activated human neutrophils which may be relevant to the pathophysiology of cardiac failure.

ALTERATIONS IN CARDIOMYOCYTE FUNCTION AFTER PULMONARY TREATMENT WITH STAINLESS STEEL WELDING FUME IN RATS

PubMed Central

Popstojanov, Risto; Antonini, James M.; Salmen, Rebecca; Ye, Morgan; Zheng, Wen; Castranova, Vincent; Fekedulegn, Desta B.; Kan, Hong

2015-01-01

Welding fume is composed of a complex of different metal particulates. Pulmonary exposure to different welding fumes may exert a negative impact on cardiac function, although the underlying mechanisms remain unclear. To explore the effect of welding fumes on cardiac function, Sprague-Dawley rats were exposed by intratracheal instillation to 2 mg/rat of manual metal arc hard surfacing welding fume (MMA-HS) once per week for 7 wk. Control rats received saline. Cardiomyocytes were isolated enzymatically at d 1 and 7 postexposure. Intracellular calcium ([Ca2+]i) transients (fluorescence ratio) were measured on the stage of an inverted phase-contrast microscope using a myocyte calcium imaging/cell length system. Phosphorylation levels of cardiac troponin I (cTnI) were determined by Western blot. The levels of nonspecific inflammatory marker C-reactive protein (CRP) and proinflammatory cytokine interleukin-6 (IL-6) in serum were measured by enzyme-linked immunosorbent assay (ELISA). Contraction of isolated cardiomyocytes was significantly reduced at d 1 and d 7 postexposure. Intracellular calcium levels were decreased in response to extracellular calcium stimulation at d 7 postexposure. Changes of intracellular calcium levels after isoprenaline hydrochloride (ISO) stimulation were not markedly different between groups at either time point. Phosphorylation levels of cTnI in the left ventricle were significantly lower at d 1 post-exposure. The serum levels of CRP were not markedly different between groups at either time point. Serum levels of IL-6 were not detectable in both groups. Cardiomyocyte alterations observed after welding fume treatment were mainly due to alterations in intracellular calcium handling and phosphorylation levels of cTnI. PMID:24786677

Alterations in cardiomyocyte function after pulmonary treatment with stainless steel welding fume in rats.

PubMed

Popstojanov, Risto; Antonini, James M; Salmen, Rebecca; Ye, Morgan; Zheng, Wen; Castranova, Vincent; Fekedulegn, Desta B; Kan, Hong

2014-01-01

Welding fume is composed of a complex of different metal particulates. Pulmonary exposure to different welding fumes may exert a negative impact on cardiac function, although the underlying mechanisms remain unclear. To explore the effect of welding fumes on cardiac function, Sprague-Dawley rats were exposed by intratracheal instillation to 2 mg/rat of manual metal arc hard surfacing welding fume (MMA-HS) once per week for 7 wk. Control rats received saline. Cardiomyocytes were isolated enzymatically at d 1 and 7 postexposure. Intracellular calcium ([Ca(2+)]i) transients (fluorescence ratio) were measured on the stage of an inverted phase-contrast microscope using a myocyte calcium imaging/cell length system. Phosphorylation levels of cardiac troponin I (cTnI) were determined by Western blot. The levels of nonspecific inflammatory marker C-reactive protein (CRP) and proinflammatory cytokine interleukin-6 (IL-6) in serum were measured by enzyme-linked immunosorbent assay (ELISA). Contraction of isolated cardiomyocytes was significantly reduced at d 1 and d 7 postexposure. Intracellular calcium levels were decreased in response to extracellular calcium stimulation at d 7 postexposure. Changes of intracellular calcium levels after isoprenaline hydrochloride (ISO) stimulation were not markedly different between groups at either time point. Phosphorylation levels of cTnI in the left ventricle were significantly lower at d 1 postexposure. The serum levels of CRP were not markedly different between groups at either time point. Serum levels of IL-6 were not detectable in both groups. Cardiomyocyte alterations observed after welding fume treatment were mainly due to alterations in intracellular calcium handling and phosphorylation levels of cTnI.

m-AAA proteases, mitochondrial calcium homeostasis and neurodegeneration

PubMed Central

Patron, Maria; Sprenger, Hans-Georg; Langer, Thomas

2018-01-01

The function of mitochondria depends on ubiquitously expressed and evolutionary conserved m-AAA proteases in the inner membrane. These ATP-dependent peptidases form hexameric complexes built up of homologous subunits. AFG3L2 subunits assemble either into homo-oligomeric isoenzymes or with SPG7 (paraplegin) subunits into hetero-oligomeric proteolytic complexes. Mutations in AFG3L2 are associated with dominant spinocerebellar ataxia (SCA28) characterized by the loss of Purkinje cells, whereas mutations in SPG7 cause a recessive form of hereditary spastic paraplegia (HSP7) with motor neurons of the cortico-spinal tract being predominantly affected. Pleiotropic functions have been assigned to m-AAA proteases, which act as quality control and regulatory enzymes in mitochondria. Loss of m-AAA proteases affects mitochondrial protein synthesis and respiration and leads to mitochondrial fragmentation and deficiencies in the axonal transport of mitochondria. Moreover m-AAA proteases regulate the assembly of the mitochondrial calcium uniporter (MCU) complex. Impaired degradation of the MCU subunit EMRE in AFG3L2-deficient mitochondria results in the formation of deregulated MCU complexes, increased mitochondrial calcium uptake and increased vulnerability of neurons for calcium-induced cell death. A reduction of calcium influx into the cytosol of Purkinje cells rescues ataxia in an AFG3L2-deficient mouse model. In this review, we discuss the relationship between the m-AAA protease and mitochondrial calcium homeostasis and its relevance for neurodegeneration and describe a novel mouse model lacking MCU specifically in Purkinje cells. Our results pledge for a novel view on m-AAA proteases that integrates their pleiotropic functions in mitochondria to explain the pathogenesis of associated neurodegenerative disorders. PMID:29451229

m-AAA proteases, mitochondrial calcium homeostasis and neurodegeneration.

PubMed

Patron, Maria; Sprenger, Hans-Georg; Langer, Thomas

2018-03-01

The function of mitochondria depends on ubiquitously expressed and evolutionary conserved m-AAA proteases in the inner membrane. These ATP-dependent peptidases form hexameric complexes built up of homologous subunits. AFG3L2 subunits assemble either into homo-oligomeric isoenzymes or with SPG7 (paraplegin) subunits into hetero-oligomeric proteolytic complexes. Mutations in AFG3L2 are associated with dominant spinocerebellar ataxia (SCA28) characterized by the loss of Purkinje cells, whereas mutations in SPG7 cause a recessive form of hereditary spastic paraplegia (HSP7) with motor neurons of the cortico-spinal tract being predominantly affected. Pleiotropic functions have been assigned to m-AAA proteases, which act as quality control and regulatory enzymes in mitochondria. Loss of m-AAA proteases affects mitochondrial protein synthesis and respiration and leads to mitochondrial fragmentation and deficiencies in the axonal transport of mitochondria. Moreover m-AAA proteases regulate the assembly of the mitochondrial calcium uniporter (MCU) complex. Impaired degradation of the MCU subunit EMRE in AFG3L2-deficient mitochondria results in the formation of deregulated MCU complexes, increased mitochondrial calcium uptake and increased vulnerability of neurons for calcium-induced cell death. A reduction of calcium influx into the cytosol of Purkinje cells rescues ataxia in an AFG3L2-deficient mouse model. In this review, we discuss the relationship between the m-AAA protease and mitochondrial calcium homeostasis and its relevance for neurodegeneration and describe a novel mouse model lacking MCU specifically in Purkinje cells. Our results pledge for a novel view on m-AAA proteases that integrates their pleiotropic functions in mitochondria to explain the pathogenesis of associated neurodegenerative disorders.

Dependence of Ca outflow and depression of frog myocardium contraction on ryodipine concentration.

PubMed

Narusevicius, E; Gendviliene, V; Macianskiene, R; Hmelj-Dunai, G; Velena, A; Duburs, G

1988-02-01

The effect of ryodipine on calcium outflow from tissues, on contraction force, the duration of action potentials and the relaxation phase time-constant in the contraction cycles of myocardial strips was studied using frog heart preparations. It was found that calcium outflow (delta Ca) as a function on ryodipine concentration can be represented as: (formula; see text) A linear correlation exists between Ca2+, contraction blocking and the shortening of the action potential in the presence of various ryodipine concentrations. Ryodipine (10(-5) mol/l) decreased the relaxation time-constant by about 20% as compared to controls. It was concluded that calcium outflow from myocardial tissues in response to ryodipine is due to blockade of calcium entry into the cells and their output through the Na+--Ca2+ exchange system. Frog heart myocardial contractions are essentially under the control of calcium entry through sarcolemmal calcium channels.

Stable prenucleation mineral clusters are liquid-like ionic polymers

PubMed Central

Demichelis, Raffaella; Raiteri, Paolo; Gale, Julian D.; Quigley, David; Gebauer, Denis

2011-01-01

Calcium carbonate is an abundant substance that can be created in several mineral forms by the reaction of dissolved carbon dioxide in water with calcium ions. Through biomineralization, organisms can harness and control this process to form various functional materials that can act as anything from shells through to lenses. The early stages of calcium carbonate formation have recently attracted attention as stable prenucleation clusters have been observed, contrary to classical models. Here we show, using computer simulations combined with the analysis of experimental data, that these mineral clusters are made of an ionic polymer, composed of alternating calcium and carbonate ions, with a dynamic topology consisting of chains, branches and rings. The existence of a disordered, flexible and strongly hydrated precursor provides a basis for explaining the formation of other liquid-like amorphous states of calcium carbonate, in addition to the non-classical behaviour during growth of amorphous calcium carbonate. PMID:22186886

Novel calcium recognition constructions in proteins: Calcium blade and EF-hand zone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Denesyuk, Alexander I., E-mail: adenesyu@abo.fi; Institute for Biological Instrumentation of the Russian Academy of Sciences, Pushchino 142290; Permyakov, Sergei E.

Metal ions can regulate various cell processes being first, second or third messengers, and some of them, especially transition metal ions, take part in catalysis in many enzymes. As an intracellular ion, Ca{sup 2+} is involved in many cellular functions from fertilization and contraction, cell differentiation and proliferation, to apoptosis and cancer. Here, we have identified and described two novel calcium recognition environments in proteins: the calcium blade zone and the EF-hand zone, common to 12 and 8 different protein families, respectively. Each of the two environments contains three distinct structural elements: (a) the well-known characteristic Dx[DN]xDG motif; (b) anmore » adjacent structurally identical segment, which binds metal ion in the same way between the calcium blade zone and the EF-hand zone; and (c) the following structurally variable segment, which distinguishes the calcium blade zone from the EF-hand zone. Both zones have sequence insertions between the last residue of the zone and calcium-binding residues in positions V or VI. The long insertion often connects the active and the calcium-binding sites in proteins. Using the structurally identical segments as an anchor, we were able to construct the classical calmodulin type EF-hand calcium-binding site out of two different calcium-binding motifs from two unrelated proteins.« less

Action of cholecystokinin and cholinergic agents on calcium transport in isolated pancreatic acinar cells.

PubMed Central

Gardner, J D; Conlon, T P; Kleveman, H L; Adams, T D; Ondetti, M A

1975-01-01

COOH-terminal octapeptide of cholecystokinin (CCK-octapeptide) and the cholinergic agent carbamylcholine each produced a fourfold stimulation of calcium outflux in guinea pig isolated pancreatic acinar cells. Neither agent altered calcium influx. Stimulation of calcium outflux was rapid and specific, was abolished by reducing the incubation temperature to 4 degrees C, and was a saturable function of the secretagogue concentration. The concentrations of CCK-octapeptide and carbamylcholine that produced half-maximal stimulation of calcium outflux were 3.1 x 10(-10) M and 4.9 x 10(-5) M, respectively. The cholinergic antagonist antropine competitively inhibited carbamylcholine stimulation of calcium outflux but did not alter stimulation produced by CCK-octapeptide. Stimulation of calcium outflux by maximal concentrations of carbamycholine plus CCK-octapeptide was the same as that produced by a maximal concentration of either agent alone.Calcium outflux became refractory to stimulation by secretagogues, and incubation with either CCK-ostapeptide or carbamylcholine produced a refractoriness to both agents. The relative potencies with CCK and its related fragments stimulated calcium outflux were CCK-octapeptide greater than heptapeptide greater than CCK greater than hexapeptide = gastrin. Secretin, glucagon, and vasoactive intestinal peptide, at concentrations as high as 10(-5) M, failed to alter calcium outflux and did not affect stimulation by CCK-octapeptide or by carbamycholine. Images PMID:1150877

Intraciliary calcium oscillations initiate vertebrate left-right asymmetry.

PubMed

Yuan, Shiaulou; Zhao, Lu; Brueckner, Martina; Sun, Zhaoxia

2015-03-02

Bilateral symmetry during vertebrate development is broken at the left-right organizer (LRO) by ciliary motility and the resultant directional flow of extracellular fluid. However, how ciliary motility is perceived and transduced into asymmetrical intracellular signaling at the LRO remains controversial. Previous work has indicated that sensory cilia and polycystin-2 (Pkd2), a cation channel, are required for sensing ciliary motility, yet their function and the molecular mechanism linking both to left-right signaling cascades are unknown. Here we report novel intraciliary calcium oscillations (ICOs) at the LRO that connect ciliary sensation of ciliary motility to downstream left-right signaling. Utilizing cilia-targeted genetically encoded calcium indicators in live zebrafish embryos, we show that ICOs depend on Pkd2 and are left-biased at the LRO in response to ciliary motility. Asymmetric ICOs occur with onset of LRO ciliary motility, thus representing the earliest known LR asymmetric molecular signal. Suppression of ICOs using a cilia-targeted calcium sink reveals that they are essential for LR development. These findings demonstrate that intraciliary calcium initiates LR development and identify cilia as a functional ion signaling compartment connecting ciliary motility and flow to molecular LR signaling. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inference of neuronal network spike dynamics and topology from calcium imaging data

PubMed Central

Lütcke, Henry; Gerhard, Felipe; Zenke, Friedemann; Gerstner, Wulfram; Helmchen, Fritjof

2013-01-01

Two-photon calcium imaging enables functional analysis of neuronal circuits by inferring action potential (AP) occurrence (“spike trains”) from cellular fluorescence signals. It remains unclear how experimental parameters such as signal-to-noise ratio (SNR) and acquisition rate affect spike inference and whether additional information about network structure can be extracted. Here we present a simulation framework for quantitatively assessing how well spike dynamics and network topology can be inferred from noisy calcium imaging data. For simulated AP-evoked calcium transients in neocortical pyramidal cells, we analyzed the quality of spike inference as a function of SNR and data acquisition rate using a recently introduced peeling algorithm. Given experimentally attainable values of SNR and acquisition rate, neural spike trains could be reconstructed accurately and with up to millisecond precision. We then applied statistical neuronal network models to explore how remaining uncertainties in spike inference affect estimates of network connectivity and topological features of network organization. We define the experimental conditions suitable for inferring whether the network has a scale-free structure and determine how well hub neurons can be identified. Our findings provide a benchmark for future calcium imaging studies that aim to reliably infer neuronal network properties. PMID:24399936

Calcium-sensing receptor (CASR) is involved in porcine in vitro fertilisation and early embryo development.

PubMed

Liu, C; Liu, Y; Larsen, K; Hou, Y P; Callesen, H

2018-01-01

It has been demonstrated that extracellular calcium is necessary in fertilisation and embryo development but the mechanism is still not well understood. The present study mainly focussed on the extracellular calcium effector called the calcium-sensing receptor (CASR) and examined its expression in porcine gametes and embryos and its function during fertilisation and early embryo development. By using reverse transcription polymerase chain reaction, CASR was found to be expressed in porcine oocytes, spermatozoa and embryos at different developmental stages. Functionally, medium supplementation with a CASR agonist or an antagonist during in vitro fertilisation (IVF) and in vitro culture (IVC) was tested. During fertilisation, the presence of a CASR agonist increased sperm penetration rate and decreased polyspermy rate leading to an increased normal fertilisation rate. During embryo development, for the IVF embryos, agonist treatment during IVC significantly increased cleavage rate and blastocyst formation rate compared with the control group. Furthermore, parthenogenetically activated embryos showed similar results with lower cleavage and blastocyst formation rates in the antagonist group than in the other groups. It was concluded that CASR, as the effector of extracellular calcium, modulates porcine fertilisation and early embryo development.

Action potentials drive body wall muscle contractions in Caenorhabditis elegans

PubMed Central

Gao, Shangbang; Zhen, Mei

2011-01-01

The sinusoidal locomotion exhibited by Caenorhabditis elegans predicts a tight regulation of contractions and relaxations of its body wall muscles. Vertebrate skeletal muscle contractions are driven by voltage-gated sodium channel–dependent action potentials. How coordinated motor outputs are regulated in C. elegans, which does not have voltage-gated sodium channels, remains unknown. Here, we show that C. elegans body wall muscles fire all-or-none, calcium-dependent action potentials that are driven by the L-type voltage-gated calcium and Kv1 voltage-dependent potassium channels. We further demonstrate that the excitatory and inhibitory motoneuron activities regulate the frequency of action potentials to coordinate muscle contraction and relaxation, respectively. This study provides direct evidence for the dual-modulatory model of the C. elegans motor circuit; moreover, it reveals a mode of motor control in which muscle cells integrate graded inputs of the nervous system and respond with all-or-none electrical signals. PMID:21248227

Hypothyrodism as a risk factor of periodontitis and its relation with vitamin D deficiency: mini-review of literature and a case report

PubMed Central

Yussif, Nermin M.; El-Mahdi, Fatema Mohammed; Wagih, Rasha

2017-01-01

Summary Objective The purpose of this report is to investigate the role and efficiency of the intra-ligamentary injection of vitamin D and calcium in the treatment of chronic periodontitis associated with hypothyroidism. Design A 43-year-old female with suspected hypothyroidism who revealed severe chronic periodontitis with grade III mobility. Pre-operative periodontal and systemic control preceded the used intervention. After 3 months, intra-ligamentary injectable vitamin D with calcium was introduced. Results Clinical evaluation revealed great improvement of the injected sites. Marked reduction of mobility, pocket depth and bleeding were detected. Conclusions Injectabe vitamin D is an adjunctive treatment modality that needs to be discovered in another way. It may provide further solutions for the periodontal regeneration problem. Clinical studies with large sample sizes and long term follow up are needed. PMID:29354159

Effect of exercise training on Ca2+ release units of left ventricular myocytes of spontaneously hypertensive rats.

PubMed

Carneiro-Júnior, M A; Quintão-Júnior, J F; Drummond, L R; Lavorato, V N; Drummond, F R; Amadeu, M A; Oliveira, E M; Felix, L B; Cruz, J S; Mill, J G; Natali, A J; Prímola-Gomes, T N

2014-08-29

In cardiomyocytes, calcium (Ca2+) release units comprise clusters of intracellular Ca2+ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca2+ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca2+ sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s) and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ΔF/F0), full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm), total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms), time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms), and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms). These changes were partially reversed in HT rats (frequency of Ca2+ sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F0, full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of left ventricular myocytes.

Functionally Graded Adhesives for Composite Joints

NASA Technical Reports Server (NTRS)

Stapleton, Scott E.; Waas, Anthony M.; Arnold, Steven M.

2012-01-01

Adhesives with functionally graded material properties are being considered for use in adhesively bonded joints to reduce the peel stress concentrations located near adherend discontinuities. Several practical concerns impede the actual use of such adhesives. These include increased manufacturing complications, alterations to the grading due to adhesive flow during manufacturing, and whether changing the loading conditions significantly impact the effectiveness of the grading. An analytical study is conducted to address these three concerns. An enhanced joint finite element, which uses an analytical formulation to obtain exact shape functions, is used to model the joint. Furthermore, proof of concept testing is conducted to show the potential advantages of functionally graded adhesives. In this study, grading is achieved by strategically placing glass beads within the adhesive layer at different densities along the joint.

Density and mechanical properties of calcium aluminate cement

NASA Astrophysics Data System (ADS)

Ahmed, Syed Taqi Uddin; Ahmmad, Shaik Kareem

2018-04-01

Calcium aluminate cements are a special type of cements which have their composition mainly dominated by the presence of Monocalcium Aluminates. In the present paper for the first time we have shown theoretical density and elastic constants for various calcium aluminate cements. The density of the present CAS decrease with aluminates presents in the cement. Using the density data, the elastic moduli namely Young's modulus, bulk and shear modulus show strong linear dependence as a function of compositional parameter.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bizzozero, Julien, E-mail: julien.bizzozero@gmail.com; Scrivener, Karen L.

This paper reports a study of ternary blends composed of calcium aluminate cement, calcium sulfate hemihydrate and limestone. Compressive strength tests and hydration kinetics were studied as a function of limestone and calcium sulfate content. The phase evolution and the total porosity were followed and compared to thermodynamic simulation to understand the reactions involved and the effect of limestone on these binders. The reaction of limestone leads to the formation of hemicarboaluminate and monocarboaluminate. Increasing the ratio between sulfate and aluminate decreases the extent of limestone reaction.

The Role of Calcium in Osteoporosis

NASA Technical Reports Server (NTRS)

Arnaud, C. D.; Sanchez, S. D.

1991-01-01

Calcium requirements may vary throughout the lifespan. During the growth years and up to age 25 to 30, it is important to maximize dietary intake of calcium to maintain positive calcium balance and achieve peak bone mass, thereby possibly decreasing the risk of fracture when bone is subsequently lost. Calcium intake need not be greater than 800 mg/day during the relatively short period of time between the end of bone building and the onset of bone loss (30 to 40 years). Starting at age 40 to 50, both men and women lose bone slowly, but women lose bone more rapidly around the menopause and for about 10 years after. Intestinal calcium absorption and the ability to adapt to low calcium diets are impaired in many postmenopausal women and elderly persons owing to a suspected functional or absolute decrease in the ability of the kidney to produce 1,25(OH)2D2. The bones then become more and more a source of calcium to maintain critical extracellular fluid calcium levels. Excessive dietary intake of protein and fiber may induce significant negative calcium balance and thus increase dietary calcium requirements. Generally, the strongest risk factors for osteoporosis are uncontrollable (e.g., sex, age, and race) or less controllable (e.g., disease and medications). However, several factors such as diet, physical activity, cigarette smoking, and alcohol use are lifestyle related and can be modified to help reduce the risk of osteoporosis.

The onset of calcium carbonate nucleation: a density functional theory molecular dynamics and hybrid microsolvation/continuum study.

PubMed

Di Tommaso, Devis; de Leeuw, Nora H

2008-06-12

Density functional theory (Perdew-Burke-Ernzerhof) based methods have been used to study the structure and hydration environment of the building blocks of CaCO 3 in aqueous solutions of calcium bicarbonate and calcium carbonate. Car-Parrinello molecular dynamics simulations of Ca(2+)/CO3(2-) and Ca (2+)/HCO3(-) in explicit water were performed to investigate the formation of CaCO3 and the hydration shell of the solvated hetero-ion pair. Our simulations show that the formation of the monomer of CaCO3 occurs with an associative mechanism and that the dominant building block of calcium (bi)carbonate in aqueous solution is Ca[eta(1)-(H)CO3](H2O)5, i.e., the preferred hydration number is five, while the (bi)carbonate is coordinated to the calcium in a monodentate mode. This result agrees with static calculations, where a hybrid approach using a combination of explicit solvent molecules and a polarizable continuum model has been applied to compute the solvation free energies of calcium bicarbonate species. Furthermore, the discrete-continuum calculations predict that the Ca(HCO3)2 and Ca(HCO3)3(-) species are stable in an aqueous environment preferentially as Ca(HCO3)2(H2O)4 and Ca(HCO3)3(H2O)2(-), respectively.

Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation.

PubMed

Minor, Daniel L; Findeisen, Felix

2010-01-01

Voltage-gated calcium channels (CaVs) are large, transmembrane multiprotein complexes that couple membrane depolarization to cellular calcium entry. These channels are central to cardiac action potential propagation, neurotransmitter and hormone release, muscle contraction, and calcium-dependent gene transcription. Over the past six years, the advent of high-resolution structural studies of CaV components from different isoforms and CaV modulators has begun to reveal the architecture that underlies the exceptionally rich feedback modulation that controls CaV action. These descriptions of CaV molecular anatomy have provided new, structure-based insights into the mechanisms by which particular channel elements affect voltage-dependent inactivation (VDI), calcium‑dependent inactivation (CDI), and calcium‑dependent facilitation (CDF). The initial successes have been achieved through structural studies of soluble channel domains and modulator proteins and have proven most powerful when paired with biochemical and functional studies that validate ideas inspired by the structures. Here, we review the progress in this growing area and highlight some key open challenges for future efforts.

Calcification and photosynthesis of the coral acropora cervicornis under calcium limited conditions

NASA Technical Reports Server (NTRS)

Rathfon, Megan; Brewer, Debbie

1997-01-01

Differing hypothesis about the function of calcification are based on an interesting dilemma. Is the purpose of calcification mainly a structural and protective one or does calcification serve other functions? Does photosynthesis increase carbonate ion activity and cause calcification or does calcification increase CO2 levels and stimulate photsynthesis? It is proposed that calcification in corals is not dependent upon photosynthesis but upon calcium levels in the water. Under normal ocean conditions, corals convert a certain percentage of energy to photosynthesis and respiration and another percentage to calcification. As corals become nutrient stressed, particularly calcium limited, the ratio of photosynthesis to calcification shifts towards calcification in order to generate protons. The protons generated during calcification may stimulate photosynthesis and aid in the uptake of nutrients and biocarbonates. The results of the calcification experiment show a trend towards increased calcification and decreased photosynthesis when the coral Acropora cervicornis is calcium limited, but the data are inconclusive and further research is needed.

Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease

PubMed Central

Nguyen, Tammy T.; Oh, Sang S.; Weaver, David; Lewandowska, Agnieszka; Maxfield, Dane; Schuler, Max-Hinderk; Smith, Nathan K.; Macfarlane, Jane; Saunders, Gerald; Palmer, Cheryl A.; Debattisti, Valentina; Koshiba, Takumi; Pulst, Stefan; Feldman, Eva L.; Hajnóczky, György; Shaw, Janet M.

2014-01-01

Defective mitochondrial distribution in neurons is proposed to cause ATP depletion and calcium-buffering deficiencies that compromise cell function. However, it is unclear whether aberrant mitochondrial motility and distribution alone are sufficient to cause neurological disease. Calcium-binding mitochondrial Rho (Miro) GTPases attach mitochondria to motor proteins for anterograde and retrograde transport in neurons. Using two new KO mouse models, we demonstrate that Miro1 is essential for development of cranial motor nuclei required for respiratory control and maintenance of upper motor neurons required for ambulation. Neuron-specific loss of Miro1 causes depletion of mitochondria from corticospinal tract axons and progressive neurological deficits mirroring human upper motor neuron disease. Although Miro1-deficient neurons exhibit defects in retrograde axonal mitochondrial transport, mitochondrial respiratory function continues. Moreover, Miro1 is not essential for calcium-mediated inhibition of mitochondrial movement or mitochondrial calcium buffering. Our findings indicate that defects in mitochondrial motility and distribution are sufficient to cause neurological disease. PMID:25136135

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levendis, Y.A.; Zhu, W.; Wise, D.L.

A fundamental study was conducted on the effectiveness of the chemical calcium magnesium acetate (CMA) as a sulfur capture agent during combustion of pulverized coal. It was based on high-temperature laboratory-bench experiments with the scope of exploring the use of CMA as a dry scrubbing'' medium for in-boiler injection. Two methods of CMA introduction in the furnace were considered: dry-spraying fine powders of the chemical and wet-spraying aqueous solutions to generate fine aerosols. It considered conditions pertinent to post-flame in-boiler injection of CMA to identify optimum temperatures and residence times. In addition to the versatility of the water-soluble CMA tomore » enable spray drying injection and therefore eliminate grinding costs, there are other attractive features. Mainly, its ability to form highly cenospheric, popcorn''-like, oxide particles on heating to high temperatures. These cenospheres possess thin, porous walls with blowholes that enable penetration of the SO[sub 2] in the interior of the particle which promotes high sorbent utilization. SO[sub 2] captures in the order of 90% were achieved with dry-injection of the chemical at furnace gas temperatures of about 1,000[degree]C, a Ca/S ratio of 2, and particle size of [approximately] 50[mu]m. Moreover, CMA was superior (by over 40%) to either CaCO[sub 3] or Ca(OH)[sub 2] in sulfur capture effectiveness per unit mass of calcium. This commercially obtained CMA was even superior to reagent-grade calcium acetate (by as much as 30%), again per unit mass of calcium. The utilization of CMA and calcium acetate depended on the cenosphere wall thickness, rather than the particle size and, thus, outperformed other sorbents regardless of the size of the resulting oxide particles.« less

Calcium signaling properties of a thyrotroph cell line, mouse TαT1 cells.

PubMed

Tomić, Melanija; Bargi-Souza, Paula; Leiva-Salcedo, Elias; Nunes, Maria Tereza; Stojilkovic, Stanko S

2015-12-01

TαT1 cells are mouse thyrotroph cell line frequently used for studies on thyroid-stimulating hormone beta subunit gene expression and other cellular functions. Here we have characterized calcium-signaling pathways in TαT1 cells, an issue not previously addressed in these cells and incompletely described in native thyrotrophs. TαT1 cells are excitable and fire action potentials spontaneously and in response to application of thyrotropin-releasing hormone (TRH), the native hypothalamic agonist for thyrotrophs. Spontaneous electrical activity is coupled to small amplitude fluctuations in intracellular calcium, whereas TRH stimulates both calcium mobilization from intracellular pools and calcium influx. Non-receptor-mediated depletion of intracellular pool also leads to a prominent facilitation of calcium influx. Both receptor and non-receptor stimulated calcium influx is substantially attenuated but not completely abolished by inhibition of voltage-gated calcium channels, suggesting that depletion of intracellular calcium pool in these cells provides a signal for both voltage-independent and -dependent calcium influx, the latter by facilitating the pacemaking activity. These cells also express purinergic P2Y1 receptors and their activation by extracellular ATP mimics TRH action on calcium mobilization and influx. The thyroid hormone triiodothyronine prolongs duration of TRH-induced calcium spikes during 30-min exposure. These data indicate that TαT1 cells are capable of responding to natively feed-forward TRH signaling and intrapituitary ATP signaling with acute calcium mobilization and sustained calcium influx. Amplification of TRH-induced calcium signaling by triiodothyronine further suggests the existence of a pathway for positive feedback effects of thyroid hormones probably in a non-genomic manner. Published by Elsevier Ltd.

Protein kinases as mediators of fluid shear stress stimulated signal transduction in endothelial cells: a hypothesis for calcium-dependent and calcium-independent events activated by flow.

PubMed

Berk, B C; Corson, M A; Peterson, T E; Tseng, H

1995-12-01

Fluid shear stress regulates endothelial cell function, but the signal transduction mechanisms involved in mechanotransduction remain unclear. Recent findings demonstrate that several intracellular kinases are activated by mechanical forces. In particular, members of the mitogen-activated protein (MAP) kinase family are stimulated by hyperosmolarity, stretch, and stress such as heat shock. We propose a model for mechanotransduction in endothelial cells involving calcium-dependent and calcium-independent protein kinase pathways. The calcium-dependent pathway involves activation of phospholipase C, hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), increases in intracellular calcium and stimulation of kinases such as calcium-calmodulin and C kinases (PKC). The calcium-independent pathway involves activation of a small GTP-binding protein and stimulation of calcium-independent PKC and MAP kinases. The calcium-dependent pathway mediates the rapid, transient response to fluid shear stress including activation of nitric oxide synthase (NOS) and ion transport. In contrast, the calcium-independent pathway mediates a slower response including the sustained activation of NOS and changes in cell morphology and gene expression. We propose that focal adhesion complexes link the calcium-dependent and calcium-independent pathways by regulating activity of phosphatidylinositol 4-phosphate (PIP) 5-kinase (which regulates PIP2 levels) and p125 focal adhesion kinase (FAK, which phosphorylates paxillin and interacts with cytoskeletal proteins). This model predicts that dynamic interactions between integrin molecules present in focal adhesion complexes and membrane events involved in mechanotransduction will be integrated by calcium-dependent and calcium-independent kinases to generate intracellular signals involved in the endothelial cell response to flow.

Intestinal absorption and renal reabsorption of calcium throughout postnatal development

PubMed Central

Beggs, Megan R

2017-01-01

Calcium is vital for many physiological functions including bone mineralization. Postnatal deposition of calcium into bone is greatest in infancy and continues through childhood and adolescence until peek mineral density is reached in early adulthood. Thereafter, bone mineral density remains static until it eventually declines in later life. A positive calcium balance, i.e. more calcium absorbed than excreted, is crucial to bone deposition during growth and thus to peek bone mineral density. Dietary calcium is absorbed from the intestine into the blood. It is then filtered by the renal glomerulus and either reabsorbed by the tubule or excreted in the urine. Calcium can be (re)absorbed across intestinal and renal epithelia via both transcellular and paracellular pathways. Current evidence suggests that significant intestinal and renal calcium transport changes occur throughout development. However, the molecular details of these alterations are incompletely delineated. Here we first briefly review the current model of calcium transport in the intestine and renal tubule in the adult. Then, we describe what is known with regard to calcium handling through postnatal development, and how alterations may aid in mediating a positive calcium balance. The role of transcellular and paracellular calcium transport pathways and the contribution of specific intestinal and tubular segments vary with age. However, the current literature highlights knowledge gaps in how specifically intestinal and renal calcium (re)absorption occurs early in postnatal development. Future research should clarify the specific changes in calcium transport throughout early postnatal development including mediators of these alterations enabling appropriate bone mineralization. Impact statement This mini review outlines the current state of knowledge pertaining to the molecules and mechanisms maintaining a positive calcium balance throughout postnatal development. This process is essential to achieving optimal bone mineral density in early adulthood, thereby lowering the lifetime risk of osteoporosis. PMID:28346014

Association between Plasma 25-Hydroxyvitamin D, Ancestry and Aggressive Prostate Cancer among African Americans and European Americans in PCaP

PubMed Central

Steck, Susan E.; Arab, Lenore; Zhang, Hongmei; Bensen, Jeannette T.; Fontham, Elizabeth T. H.; Johnson, Candace S.; Mohler, James L.; Smith, Gary J.; Su, Joseph L.; Trump, Donald L.; Woloszynska-Read, Anna

2015-01-01

Background African Americans (AAs) have lower circulating 25-hydroxyvitamin D3 [25(OH)D3] concentrations and higher prostate cancer (CaP) aggressiveness than other racial/ethnic groups. The purpose of the current study was to examine the relationship between plasma 25(OH)D3, African ancestry and CaP aggressiveness among AAs and European Americans (EAs). Methods Plasma 25(OH)D3 was measured using LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in 537 AA and 663 EA newly-diagnosed CaP patients from the North Carolina-Louisiana Prostate Cancer Project (PCaP) classified as having either ‘high’ or ‘low’ aggressive disease based on clinical stage, Gleason grade and prostate specific antigen at diagnosis. Mean plasma 25(OH)D3 concentrations were compared by proportion of African ancestry. Logistic regression was used to calculate multivariable adjusted odds ratios (OR) and 95% confidence intervals (95%CI) for high aggressive CaP by tertile of plasma 25(OH)D3. Results AAs with highest percent African ancestry (>95%) had the lowest mean plasma 25(OH)D3 concentrations. Overall, plasma 25(OH)D3 was associated positively with aggressiveness among AA men, an association that was modified by calcium intake (ORT3vs.T1: 2.23, 95%CI: 1.26–3.95 among men with low calcium intake, and ORT3vs.T1: 0.19, 95%CI: 0.05–0.70 among men with high calcium intake). Among EAs, the point estimates of the ORs were <1.0 for the upper tertiles with CIs that included the null. Conclusions Among AAs, plasma 25(OH)D3 was associated positively with CaP aggressiveness among men with low calcium intake and inversely among men with high calcium intake. The clinical significance of circulating concentrations of 25(OH)D3 and interactions with calcium intake in the AA population warrants further study. PMID:25919866

Oxidative stress and protein aggregation during biological aging.

PubMed

Squier, T C

2001-09-01

Biological aging is a fundamental process that represents the major risk factor with respect to the development of cancer, neurodegenerative, and cardiovascular diseases in vertebrates. It is, therefore, evident that the molecular mechanisms of aging are fundamental to understand many disease processes. In this regard, the oxidation and nitration of intracellular proteins and the formation of protein aggregates have been suggested to underlie the loss of cellular function and the reduced ability of senescent animals to withstand physiological stresses. Since oxidatively modified proteins are thermodynamically unstable and assume partially unfolded tertiary structures that readily form aggregates, it is likely that oxidized proteins are intermediates in the formation of amyloid fibrils. It is, therefore, of interest to identify oxidatively sensitive protein targets that may play a protective role through their ability to down-regulate energy metabolism and the consequent generation of reactive oxygen species (ROS). In this respect, the maintenance of cellular calcium gradients represents a major energetic expense, which links alterations in intracellular calcium levels to ATP utilization and the associated generation of ROS through respiratory control mechanisms. The selective oxidation or nitration of the calcium regulatory proteins calmodulin and Ca-ATPase that occurs in vivo during aging and under conditions of oxidative stress may represent an adaptive response to oxidative stress that functions to down-regulate energy metabolism and the associated generation of ROS. Since these calcium regulatory proteins are also preferentially oxidized or nitrated under in vitro conditions, these results suggest an enhanced sensitivity of these critical calcium regulatory proteins, which modulate signal transduction processes and intracellular energy metabolism, to conditions of oxidative stress. Thus, the selective oxidation of critical signal transduction proteins probably represents a regulatory mechanism that functions to minimize the generation of ROS through respiratory control mechanisms. The reduction of the rate of ROS generation, in turn, will promote cellular survival under conditions of oxidative stress, when reactive oxygen and nitrogen species overwhelm cellular antioxidant defense systems, by minimizing the non-selective oxidation of a range of biomolecules. Since protein aggregation occurs if protein repair and degradative systems are unable to act upon oxidized proteins and restore cellular function, the reduction of the oxidative load on the cell by the down-regulation of the electron transport chain functions to minimize protein aggregation. Thus, ROS function as signaling molecules that fine-tune cellular metabolism through the selective oxidation or nitration of calcium regulatory proteins in order to minimize wide-spread oxidative damage and protein aggregation. Oxidative damage to cellular proteins, the loss of calcium homeostasis and protein aggregation contribute to the formation of amyloid deposits that accumulate during biological aging. Critical to understand the relationship between these processes and biological aging is the identification of oxidatively sensitive proteins that modulate energy utilization and the associated generation of ROS. In this latter respect, oxidative modifications to the calcium regulatory proteins calmodulin (CaM) and the sarco/endoplasmic reticulum Ca-ATPase (SERCA) function to down-regulate ATP utilization and the associated generation of ROS associated with replenishing intracellular ATP through oxidative phosphorylation. Reductions in the rate of ROS generation, in turn, will minimize protein oxidation and facilitate intracellular repair and degradative systems that function to eliminate damaged and partially unfolded proteins. Since the rates of protein repair or degradation compete with the rate of protein aggregation, the modulation of intracellular calcium concentrations and energy metabolism through the selective oxidation or nitration of critical signal transduction proteins (i.e. CaM or SERCA) is thought to maintain cellular function by minimizing protein aggregation and amyloid formation. Age-dependent increases in the rate of ROS generation or declines in cellular repair or degradation mechanisms will increase the oxidative load on the cell, resulting in corresponding increases in the concentrations of oxidized proteins and the associated formation of amyloid.

Inhibition of Bcl-2 Sensitizes Mitochondrial Permeability Transition Pore (MPTP) Opening in Ischemia-Damaged Mitochondria

PubMed Central

Chen, Qun; Xu, Haishan; Xu, Aijun; Ross, Thomas; Bowler, Elizabeth; Hu, Ying; Lesnefsky, Edward J.

2015-01-01

Background Mitochondria are critical to cardiac injury during reperfusion as a result of damage sustained during ischemia, including the loss of bcl-2. We asked if bcl-2 depletion not only leads to selective permeation of the outer mitochondrial membrane (MOMP) favoring cytochrome c release and programmed cell death, but also favors opening of the mitochondrial permeability transition pore (MPTP). An increase in MPTP susceptibility would support a role for bcl-2 depletion mediated cell death in the calcium overload setting of early reperfusion via MPTP as well as later in reperfusion via MOMP as myocardial calcium content normalizes. Methods Calcium retention capacity (CRC) was used to reflect the sensitivity of the MPTP opening in isolated cardiac mitochondria. To study the relationship between bcl-2 inhibition and MPTP opening, mitochondria were incubated with a bcl-2 inhibitor (HA14-1) and CRC measured. The contribution of preserved bcl-2 content to MPTP opening following ischemia-reperfusion was explored using transgenic bcl-2 overexpressed mice. Results CRC was decreased in mitochondria following reperfusion compared to ischemia alone, indicating that reperfusion further sensitizes to MPTP opening. Incubation of ischemia-damaged mitochondria with increasing HA14-1concentrations increased calcium-stimulated MPTP opening, supporting that functional inhibition of bcl-2 during simulated reperfusion favors MPTP opening. Moreover, HA14-1 sensitivity was increased by ischemia compared to non-ischemic controls. Overexpression of bcl-2 attenuated MPTP opening in following ischemia-reperfusion. HA14-1 inhibition also increased the permeability of the outer membrane in the absence of exogenous calcium, indicating that bcl-2 inhibition favors MOMP when calcium is low. Conclusions The depletion and functional inhibition of bcl-2 contributes to cardiac injury by increasing susceptibility to MPTP opening in high calcium environments and MOMP in the absence of calcium overload. Thus, ischemia-damaged mitochondria with decreased bcl-2 content are susceptible to MPTP opening in early reperfusion and MOMP later in reperfusion when cytosolic calcium has normalized. PMID:25756500

Extracellular calcium regulates protein tyrosine phosphorylation through calcium-sensing receptor (CaSR) in stallion sperm.

PubMed

Macías-García, Beatriz; Rocha, Antonio; González-Fernández, Lauro

2016-03-01

Protein tyrosine phosphorylation (PY), a hallmark of sperm capacitation, is inhibited by extracellular calcium in stallion sperm. The objective of this study was to determine the presence and influence of the calcium-sensing receptor (CaSR) in this phenomenon. First, the presence of the CaSR was demonstrated in stallion sperm. We then tested its function in these gametes using its inhibitor NPS2143 or its agonist AC34356. Sperm were capacitated for 4 hr in modified Whitten's medium with 25 mM bicarbonate plus NPS2143 and 2.4 mM calcium or AC34356 alone, followed by analysis of PY. Inhibition of CaSR with NPS2143 prevented the calcium-dependent PY inhibition in a dose-dependent manner (5, 10, and 15 μM) whereas AC34356 (100 μM) inhibited PY similarly to calcium. Stallion sperm motility and viability significantly decreased in presence of 15 μM of NPS2143 whereas only sperm motility decreased with 100 μM of AC34356. CaSR function was also studied in the complete absence of calcium by including 2 mM ethylene glycol tetraacetic acid (EGTA); under these conditions, AC34356 again inhibited PY, but this time induced a significant increase in sperm motility. Inhibition of calmodulin by W-7 did not recover the AC34356-mediated PY inhibition. When stallion sperm were incubated under capacitating conditions (calcium, bicarbonate, plus bovine serum albumin) at elevated pH (7.9 or 8.5) AC34356 did not block PY. These results thus elucidate the effect of extracellular conditions on the regulation of CaSR, and point to its modulatory role on stallion sperm PY, motility, and viability. Mol. Reprod. Dev. 83: 236-245, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Network inference from functional experimental data (Conference Presentation)

NASA Astrophysics Data System (ADS)

Desrosiers, Patrick; Labrecque, Simon; Tremblay, Maxime; Bélanger, Mathieu; De Dorlodot, Bertrand; Côté, Daniel C.

2016-03-01

Functional connectivity maps of neuronal networks are critical tools to understand how neurons form circuits, how information is encoded and processed by neurons, how memory is shaped, and how these basic processes are altered under pathological conditions. Current light microscopy allows to observe calcium or electrical activity of thousands of neurons simultaneously, yet assessing comprehensive connectivity maps directly from such data remains a non-trivial analytical task. There exist simple statistical methods, such as cross-correlation and Granger causality, but they only detect linear interactions between neurons. Other more involved inference methods inspired by information theory, such as mutual information and transfer entropy, identify more accurately connections between neurons but also require more computational resources. We carried out a comparative study of common connectivity inference methods. The relative accuracy and computational cost of each method was determined via simulated fluorescence traces generated with realistic computational models of interacting neurons in networks of different topologies (clustered or non-clustered) and sizes (10-1000 neurons). To bridge the computational and experimental works, we observed the intracellular calcium activity of live hippocampal neuronal cultures infected with the fluorescent calcium marker GCaMP6f. The spontaneous activity of the networks, consisting of 50-100 neurons per field of view, was recorded from 20 to 50 Hz on a microscope controlled by a homemade software. We implemented all connectivity inference methods in the software, which rapidly loads calcium fluorescence movies, segments the images, extracts the fluorescence traces, and assesses the functional connections (with strengths and directions) between each pair of neurons. We used this software to assess, in real time, the functional connectivity from real calcium imaging data in basal conditions, under plasticity protocols, and epileptic conditions.

Recombinant γT305A fibrinogen indicates severely impaired fibrin polymerization due to the aberrant function of hole 'A' and calcium binding sites.

PubMed

Ikeda, Minami; Kobayashi, Tamaki; Arai, Shinpei; Mukai, Saki; Takezawa, Yuka; Terasawa, Fumiko; Okumura, Nobuo

2014-08-01

We examined a 6-month-old girl with inherited fibrinogen abnormality and no history of bleeding or thrombosis. Routine coagulation screening tests showed a markedly low level of plasma fibrinogen determined by functional measurement and also a low level by antigenic measurement (functional/antigenic ratio=0.295), suggesting hypodysfibrinogenemia. DNA sequence analysis was performed, and γT305A fibrinogen was synthesized in Chinese hamster ovary cells based on the results. We then functionally analyzed and compared with that of nearby recombinant γN308K fibrinogen. DNA sequence analysis revealed a heterozygous γT305A substitution (mature protein residue number). The γT305A fibrinogen indicated markedly impaired thrombin-catalyzed fibrin polymerization both in the presence or absence of 1mM calcium ion compared with that of γN308K fibrinogen. Protection of plasmin degradation in the presence of calcium ion or Gly-Pro-Arg-Pro peptide (analogue for so-called knob 'A') and factor XIIIa-catalyzed fibrinogen crosslinking demonstrated that the calcium binding sites, hole 'a' and D:D interaction sites were all markedly impaired, whereas γN308Kwas impaired at the latter two sites. Molecular modeling demonstrated that γT305 is localized at a shorter distance than γN308 from the high affinity calcium binding site and hole 'a'. Our findings suggest that γT305 might be important for construction of the overall structure of the γ module of fibrinogen. Substitution of γT305A leads to both dysfibrinogenemic and hypofibrinogenemic characterization, namely hypodysfibrinogenemia. We have already reported that recombinant γT305A fibrinogen was synthesized normally and secreted slightly, but was significantly reduced. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bell-shaped calcium-response curves of lns(l,4,5)P3- and calcium-gated channels from endoplasmic reticulum of cerebellum

NASA Astrophysics Data System (ADS)

Bezprozvanny, Llya; Watras, James; Ehrlich, Barbara E.

1991-06-01

RELEASE of calcium from intracellular stores occurs by two pathways, an inositol 1,4,5-trisphosphate (InsP3)-gated channel1-3 and a calcium-gated channel (ryanodine receptor)4-6. Using specific antibodies, both receptors were found in Purkinje cells of cerebellum7,8. We have now compared the functional properties of the channels corresponding to the two receptors by incorporating endoplasmic reticulum vesicles from canine cerebellum into planar bilayers. InsP3-gated channels were observed most frequently. Another channel type was activated by adenine nucleotides or caffeine, inhibited by ruthenium red, and modified by ryanodine, characteristics of the ryanodine receptor/channel6. The open probability of both channel types displayed a bell-shaped curve for dependence on calcium. For the InsP3-gated channel, the maximum probability of opening occurred at 0.2 µM free calcium, with sharp decreases on either side of the maximum. Maximum activity for the ryanodine receptor/channel was maintained between 1 and 100 µM calcium. Thus, within the physiological range of cytoplasmic calcium, the InsP3-gated channel itself allows positive feed-back and then negative feedback for calcium release, whereas the ryanodine receptor/channel behaves solely as a calcium-activated channel. The existence in the same cell of two channels with different responses to calcium and different ligand sensitivities provides a basis for complex patterns of intracellular calcium regulation.

Cch1 and Mid1 Are Functionally Required for Vegetative Growth under Low-Calcium Conditions in the Phytopathogenic Ascomycete Botrytis cinerea

PubMed Central

Harren, Karin

2013-01-01

In the filamentous phytopathogen Botrytis cinerea, the Ca2+/calcineurin signaling cascade has been shown to play an important role in fungal growth, differentiation, and virulence. This study deals with the functional characterization of two components of this pathway, the putative calcium channel proteins Cch1 and Mid1. The cch1 and mid1 genes were deleted, and single and double knockout mutants were analyzed during different stages of the fungal life cycle. Our data indicate that Cch1 and Mid1 are functionally required for vegetative growth under conditions of low extracellular calcium, since the growth of both deletion mutants is strongly impaired when they are exposed to the Ca2+-chelating agents EGTA and 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA). The impact of external Ca2+ was investigated by supplementing with CaCl2 and the ionophore A23187, both of which resulted in elevated growth for all mutants. However, deletion of either gene had no impact on germination, sporulation, hyphal morphology, or virulence. By use of the aequorin reporter system to measure intracellular calcium levels, no differences between the mutant strains and the wild type were obtained. Localization studies revealed a subcellular distribution of the Mid1–green fluorescent protein (GFP) fusion protein in network-like filaments, probably the endoplasmic reticulum (ER) membranes, indicating that Mid1 is not a plasma membrane-located calcium channel in B. cinerea. PMID:23475703

α-SNAP regulates dynamic, on-site assembly and calcium selectivity of Orai1 channels

PubMed Central

Li, Peiyao; Miao, Yong; Dani, Adish; Vig, Monika

2016-01-01

Orai1 forms a highly calcium-selective pore of the calcium release activated channel, and α-SNAP is necessary for its function. Here we show that α-SNAP regulates on-site assembly of Orai1 dimers into calcium-selective multimers. We find that Orai1 is a dimer in resting primary mouse embryonic fibroblasts but displays variable stoichiometry in the plasma membrane of store-depleted cells. Remarkably, α-SNAP depletion induces formation of higher-order Orai1 oligomers, which permeate significant levels of sodium via Orai1 channels. Sodium permeation in α-SNAP–deficient cells cannot be corrected by tethering multiple Stim1 domains to Orai1 C-terminal tail, demonstrating that α-SNAP regulates functional assembly and calcium selectivity of Orai1 multimers independently of Stim1 levels. Fluorescence nanoscopy reveals sustained coassociation of α-SNAP with Stim1 and Orai1, and α-SNAP–depleted cells show faster and less constrained mobility of Orai1 within ER-PM junctions, suggesting Orai1 and Stim1 coentrapment without stable contacts. Furthermore, α-SNAP depletion significantly reduces fluorescence resonance energy transfer between Stim1 and Orai1 N-terminus but not C-terminus. Taken together, these data reveal a unique role of α-SNAP in the on-site functional assembly of Orai1 subunits and suggest that this process may, in part, involve enabling crucial low-affinity interactions between Orai1 N-terminus and Stim1. PMID:27335124

Functional Effects of Hyperthyroidism on Cardiac Papillary Muscle in Rats.

PubMed

Vieira, Fabricio Furtado; Olivoto, Robson Ruiz; Silva, Priscyla Oliveira da; Francisco, Julio Cesar; Fogaça, Rosalvo Tadeu Hochmuller

2016-12-01

Hyperthyroidism is currently recognized to affect the cardiovascular system, leading to a series of molecular and functional changes. However, little is known about the functional influence of hyperthyroidism in the regulation of cytoplasmic calcium and on the sodium/calcium exchanger (NCX) in the cardiac muscle. To evaluate the functional changes in papillary muscles isolated from animals with induced hyperthyroidism. We divided 36 Wistar rats into a group of controls and another of animals with hyperthyroidism induced by intraperitoneal T3 injection. We measured in the animals' papillary muscles the maximum contraction force, speed of contraction (+df/dt) and relaxation (-df/dt), contraction and relaxation time, contraction force at different concentrations of extracellular sodium, post-rest potentiation (PRP), and contraction force induced by caffeine. In hyperthyroid animals, we observed decreased PRP at all rest times (p < 0.05), increased +df/dt and -df/dt (p < 0.001), low positive inotropic response to decreased concentration of extracellular sodium (p < 0.001), reduction of the maximum force in caffeine-induced contraction (p < 0.003), and decreased total contraction time (p < 0.001). The maximal contraction force did not differ significantly between groups (p = 0.973). We hypothesize that the changes observed are likely due to a decrease in calcium content in the sarcoplasmic reticulum, caused by calcium leakage, decreased expression of NCX, and increased expression of a-MHC and SERCA2.

Three Dimensional Neuronal Cell Cultures More Accurately Model Voltage Gated Calcium Channel Functionality in Freshly Dissected Nerve Tissue

PubMed Central

Kisaalita, William

2012-01-01

It has been demonstrated that neuronal cells cultured on traditional flat surfaces may exhibit exaggerated voltage gated calcium channel (VGCC) functionality. To gain a better understanding of this phenomenon, primary neuronal cells harvested from mice superior cervical ganglion (SCG) were cultured on two dimensional (2D) flat surfaces and in three dimensional (3D) synthetic poly-L-lactic acid (PLLA) and polystyrene (PS) polymer scaffolds. These 2D- and 3D-cultured cells were compared to cells in freshly dissected SCG tissues, with respect to intracellular calcium increase in response to high K+ depolarization. The calcium increases were identical for 3D-cultured and freshly dissected, but significantly higher for 2D-cultured cells. This finding established the physiological relevance of 3D-cultured cells. To shed light on the mechanism behind the exaggerated 2D-cultured cells’ functionality, transcriptase expression and related membrane protein distributions (caveolin-1) were obtained. Our results support the view that exaggerated VGCC functionality from 2D cultured SCG cells is possibly due to differences in membrane architecture, characterized by uniquely organized caveolar lipid rafts. The practical implication of use of 3D-cultured cells in preclinical drug discovery studies is that such platforms would be more effective in eliminating false positive hits and as such improve the overall yield from screening campaigns. PMID:23049767

Differential calcium sensitivity in NaV 1.5 mixed syndrome mutants.

PubMed

Abdelsayed, Mena; Baruteau, Alban-Elouen; Gibbs, Karen; Sanatani, Shubhayan; Krahn, Andrew D; Probst, Vincent; Ruben, Peter C

2017-09-15

SCN5a mutations may express gain-of-function (Long QT Syndrome-3), loss-of-function (Brugada Syndrome 1) or both (mixed syndromes), depending on the mutation and environmental triggers. One such trigger may be an increase in cytosolic calcium, accompanying exercise. Many mixed syndromes mutants, including ∆KPQ, E1784K, 1795insD and Q1909R, are found in calcium-sensitive regions. Elevated cytosolic calcium attenuates gain-of-function properties in ∆KPQ, 1795insD and Q1909R, but not in E1784K. By contrast, elevated cytosolic calcium further exacerbates gain-of-function in E1784K by destabilizing slow inactivation. Action potential modelling, using a modified O'Hara Rudy model, suggests that elevated heart rate rescues action potential duration in ∆KPQ, 1795insD and Q1909R, but not in E1784K. Action potential simulations suggest that E1784K carriers have an increased intracellular sodium-to-calcium ratio under bradycardia and tachycardia conditions. Elevated cytosolic calcium, which is common during high heart rates, ameliorates or exacerbates the mixed syndrome phenotype depending on the genetic signature. Inherited arrhythmias may arise from mutations in the gene for SCN5a, which encodes the cardiac voltage-gated sodium channel, Na V 1.5. Mutants in Na V 1.5 result in Brugada Syndrome (BrS1), Long-QT Syndrome (LQT3) or mixed syndromes (an overlap of BrS1/LQT3). Exercise is a potential arrhythmogenic trigger in mixed syndromes. We aimed to determine the effects of elevated cytosolic calcium, which is common during exercise, in mixed syndrome Na V 1.5 mutants. We used whole-cell patch clamp to assess the biophysical properties of Na V 1.5 wild-type (WT), ∆KPQ, E1784K, 1795insD and Q1909R mutants in human embryonic kidney 293 cells transiently transfected with the Na V 1.5 α subunit (WT or mutants), β1 subunit and enhanced green fluorescent protein. Voltage-dependence and kinetics were measured at cytosolic calcium levels of approximately 0, 500 and 2500 nm. In silico, action potential (AP) model simulations were performed using a modified O'Hara Rudy model. Elevated cytosolic calcium attenuates the late sodium current in ∆KPQ, 1795insD and Q1909R, but not in E1784K. Elevated cytosolic calcium restores steady-state slow inactivation (SSSI) to the WT-form in Q1909R, but depolarized SSSI in E1784K. Our AP simulations showed a frequency-dependent reduction of AP duration in ∆KPQ, 1795insD and Q1909R carriers. In E1784K, AP duration is relatively prolonged at both low and high heart rates, resulting in a sodium overload. Cellular perturbations during exercise may affect BrS1/LQT3 patients differently depending on their individual genetic signature. Thus, exercise may be therapeutic or may be an arrhythmogenic trigger in some SCN5a patients. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Conformational fluctuation of Synaptotagmin-1 observed with single molecule fluorescence resonance energy transfer (smFRET)

NASA Astrophysics Data System (ADS)

Choi, Ucheor; Weninger, Keith

2008-10-01

Calcium dependent neurotransmitter release at the synapses involves a synaptic vesicle protein synaptotagmin-1, a calcium sensor, to regulate exocytosis. It has been known that Synaptotagmin-1 interacts with assembled SNARE complexes, but it is unclear how their molecular mechanisms are coupled. X-ray studies in the absence of calcium revealed a closed conformation of synaptotagmin-1 and with calcium bound to the C2 domains of synaptotagmin-3 found extensive interactions holding the domains open. Suggesting the two conformations can be the key to the two functions of synaptotagmin in regulating neurotransmission. Here we use single molecule fluorescence resonance energy transfer (smFRET) to study synaptotagmin interactions with SNARE complexes and the spontaneous conformational changes of synaptotagmin-1 when calcium is induced.

Putative calcium-binding domains of the Caenorhabditis elegans BK channel are dispensable for intoxication and ethanol activation

PubMed Central

Davis, S. J.; Scott, L. L.; Ordemann, G.; Philpo, A.; Cohn, J.; Pierce-Shimomura, J. T.

2016-01-01

Alcohol modulates the highly conserved, voltage- and calcium-activated potassium (BK) channel, which contributes to alcohol-mediated behaviors in species from worms to humans. Previous studies have shown that the calcium-sensitive domains, RCK1 and the Ca2+ bowl, are required for ethanol activation of the mammalian BK channel in vitro. In the nematode Caenorhabditis elegans, ethanol activates the BK channel in vivo, and deletion of the worm BK channel, SLO-1, confers strong resistance to intoxication. To determine if the conserved RCK1 and calcium bowl domains were also critical for intoxication and basal BK channel-dependent behaviors in C. elegans, we generated transgenic worms that express mutated SLO-1 channels predicted to have the RCK1, Ca2+ bowl or both domains rendered insensitive to calcium. As expected, mutating these domains inhibited basal function of SLO-1 in vivo as neck and body curvature of these mutants mimicked that of the BK null mutant. Unexpectedly, however, mutating these domains singly or together in SLO-1 had no effect on intoxication in C. elegans. Consistent with these behavioral results, we found that ethanol activated the SLO-1 channel in vitro with or without these domains. By contrast, in agreement with previous in vitro findings, C. elegans harboring a human BK channel with mutated calcium-sensing domains displayed resistance to intoxication. Thus, for the worm SLO-1 channel, the putative calcium-sensitive domains are critical for basal in vivo function but unnecessary for in vivo ethanol action. PMID:26113050

Assessment of Diastolic Function in Single Ventricle Patients Following the Fontan Procedure

PubMed Central

Margossian, Renee; Sleeper, Lynn A.; Pearson, Gail D.; Barker, Piers C.; Mertens, Luc; Quartermain, Michael D.; Su, Jason T.; Shirali, Girish; Chen, Shan; Colan, Steven D.

2016-01-01

Objectives Patients with functional single ventricles (FSV) following the Fontan procedure have abnormal cardiac mechanics. We sought to determine factors that influence diastolic function and to describe associations of diastolic function with current clinical status. Methods Echocardiograms were obtained as part of the Pediatric Heart Network Fontan Cross-Sectional Study. Diastolic function grade (DFG) was assessed as normal (grade 0), impaired relaxation (grade 1), pseudonormalization (grade 2), restrictive (grade 3). Studies were also classified dichotomously (restrictive pattern present or absent). Relationships between DFG and pre-Fontan variables (e.g., ventricular morphology, age at Fontan, history of volume-unloading surgery), and current status (e.g., systolic function, valvar regurgitation, exercise performance) were explored. Results DFG was calculable in 326/546 subjects (60%); mean age = 11.7±3.3 years. Overall, 32% of patients had grade 0, 9% grade 1, 37% grade 2, and 22% grade 3. Although there was no association between ventricular morphology and DFG, there was an association between ventricular morphology and E’, which was lowest in those with right ventricular morphology (p<.001); this association remained significant when using z-scores adjusted for age (p=<.001). DFG was associated with achieving maximal effort on exercise testing (p=.004); the majority (64%) of those not achieving maximal effort had DFG 2 or 3.No additional significant associations of DFG with laboratory or clinical measures were identified. Conclusion Assessment of diastolic function by current algorithms results in a high percentage of patients with abnormal DFG, but we found few clinically or statistically significant associations. This may imply a lack of impact of abnormal diastolic function upon clinical outcome in this cohort, or may indicate that the methodology may not be applicable to pediatric FSV patients. PMID:27624592

Calcium supplementation for the prevention of colorectal adenomas: A systematic review and meta-analysis of randomized controlled trials.

PubMed

Bonovas, Stefanos; Fiorino, Gionata; Lytras, Theodore; Malesci, Alberto; Danese, Silvio

2016-05-14

To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas. We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or "high-risk" adenomas), and rated each trial's risk-of-bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE. Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; random-effects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20 (95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence). Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted.

Calcium supplementation for the prevention of colorectal adenomas: A systematic review and meta-analysis of randomized controlled trials

PubMed Central

Bonovas, Stefanos; Fiorino, Gionata; Lytras, Theodore; Malesci, Alberto; Danese, Silvio

2016-01-01

AIM: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas. METHODS: We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or “high-risk” adenomas), and rated each trial’s risk-of-bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE. RESULTS: Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; random-effects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20 (95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence). CONCLUSION: Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted. PMID:27182169

European Society of Endocrinology Clinical Guideline: Treatment of chronic hypoparathyroidism in adults.

PubMed

Bollerslev, Jens; Rejnmark, Lars; Marcocci, Claudio; Shoback, Dolores M; Sitges-Serra, Antonio; van Biesen, Wim; Dekkers, Olaf M

2015-08-01

Hypoparathyroidism (HypoPT) is a rare (orphan) endocrine disease with low calcium and inappropriately low (insufficient) circulating parathyroid hormone levels, most often in adults secondary to thyroid surgery. Standard treatment is activated vitamin D analogues and calcium supplementation and not replacement of the lacking hormone, as in other hormonal deficiency states. The purpose of this guideline is to provide clinicians with guidance on the treatment and monitoring of chronic HypoPT in adults who do not have end-stage renal disease. We intend to draft a practical guideline, focusing on operationalized recommendations deemed to be useful in the daily management of patients. This guideline was developed and solely sponsored by The European Society of Endocrinology, supported by CBO (Dutch Institute for Health Care Improvement) and based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) principles as a methodological base. The clinical question on which the systematic literature search was based and for which available evidence was synthesized was: what is the best treatment for adult patients with chronic HypoPT? This systematic search found 1100 articles, which was reduced to 312 based on title and abstract. The working group assessed these for eligibility in more detail, and 32 full-text articles were assessed. For the final recommendations, other literature was also taken into account. Little evidence is available on how best to treat HypoPT. Data on quality of life and the risk of complications have just started to emerge, and clinical trials on how to optimize therapy are essentially non-existent. Most studies are of limited sample size, hampering firm conclusions. No studies are available relating target calcium levels with clinically relevant endpoints. Hence it is not possible to formulate recommendations based on strict evidence. This guideline is therefore mainly based on how patients are managed in clinical practice, as reported in small case series and based on the experiences of the authors. © 2015 European Society of Endocrinology.

Calcium binding to Procambarus clarkii sarcoplasmic calcium binding protein splice variants.

PubMed

Rohrback, Suzanne E; Wheatly, Michele G; Gillen, Christopher M

2015-01-01

Sarcoplasmic calcium binding protein (SCP) is a high-affinity calcium buffering protein expressed in muscle of crayfish and other invertebrates. In previous work, we identified three splice variants of Procambarus clarkii SCP (pcSCP1a, pcSCP1b, and pcSCP1c) that differ in a 37 amino acid region that lies mainly between the 2nd and 3ed EF-hand calcium binding domain. To evaluate the function of the proteins encoded by the pcSCP1 transcripts, we produced recombinant pcSCP1 and used tryptophan fluorescence to characterize calcium binding. Tryptophan fluorescence of pcSCP1a decreased in response to increased calcium, while tryptophan fluorescence of the pcSCP1b and pcSCP1c variants increased. We estimated calcium binding constants and Hill coefficients with two different equations: the standard Hill equation and a modified Hill equation that accounts for contributions from two different tryptophans. The approaches gave similar results. Steady-state calcium binding constants (Kd) ranged from 2.7±0.7×10(-8)M to 5.6±0.1×10(-7)M, consistent with previous work. Variants displayed significantly different apparent calcium affinities, which were decreased in the presence of magnesium. Calcium Kd was lowest for pcSCP1a and highest for pcSCP1c. Site-directed mutagenesis of pcSCP1c residues to the amino acids of pcSCP1b decreased the calcium Kd, identifying residues outside the EF-hand domains that contribute to calcium binding in crayfish SCP. Copyright © 2014 Elsevier Inc. All rights reserved.

Methods for Creating and Animating a Computer Model Depicting the Structure and Function of the Sarcoplasmic Reticulum Calcium ATPase Enzyme.

ERIC Educational Resources Information Center

Chen, Alice Y.; McKee, Nancy

1999-01-01

Describes the developmental process used to visualize the calcium ATPase enzyme of the sarcoplasmic reticulum which involves evaluating scientific information, consulting scientists, model making, storyboarding, and creating and editing in a computer medium. (Author/CCM)

Calcification resistance for photooxidatively crosslinked acellular bovine jugular vein conduits in right-side heart implantation.

PubMed

Lü, Wei-Dong; Wang, An-Ping; Wu, Zhong-Shi; Zhang, Ming; Hu, Tie-Hui; Lei, Guang-Yan; Hu, Ye-Rong

2012-10-01

This study aimed to investigate the effect of decellularization plus photooxidative crosslinking and ethanol pretreatment on bioprosthetic tissue calcification. Photooxidatively crosslinked acellular (PCA) bovine jugular vein conduits (BJVCs) and their photooxidized controls (n = 5 each) were sterilized in a graded concentration of ethanol solutions for 4 h, and used to reconstruct dog right ventricular outflow tracts. At 1-year implantation, echocardiography showed similar hemodynamic performance, but obvious calcification for the photooxidized BJVC walls. Further histological examination showed intense calcium deposition colocalized with slightly degraded elastic fibers in the photooxidized BJVC walls, with sparsely distributed punctate calcification in the valves and other areas of walls. But PCA BJVCs had apparent degradation of elastic fibers in the walls, with only sparsely distributed punctate calcification in the walls and valves. Content assay demonstrated comparable calcium content for the two groups at preimplantation, whereas less calcium for the PCA group in the walls and similar calcium in the valvular leaflets compared with the photooxidized group at 1-year retrieval. Elastin content assay presented the conduit walls of PCA group had less elastin content at preimplantation, but similar content at 1-year retrieval compared with the photooxidized group. Phospholipid analysis showed phospholipid extraction by ethanol for the PCA group was more efficacious than the photooxidized group. These results indicate that PCA BJVCs resist calcification in right-side heart implantation owing to decellularization, further photooxidative crosslinking, and subsequent phospholipid extraction by ethanol at preimplantation. Copyright © 2012 Wiley Periodicals, Inc.

Effect of desensitizing toothpastes on dentine hypersensitivity: A systematic review and meta-analysis.

PubMed

Hu, Meng-Long; Zheng, Gang; Zhang, You-Dong; Yan, Xiang; Li, Xiao-Chan; Lin, Hong

2018-05-19

To evaluate the desensitizing effect of toothpastes that contain ingredients that act against dentine hypersensitivity (DH) and to compare this effect with negative controls. Five databases were searched to identify relevant articles published up to November 27, 2017. Randomized controlled trials (RCTs) comparing desensitizing toothpastes with a toothpastes without desensitizing component in adult patients that suffer from DH were included. The risk of bias was assessed according to the Cochrane guidelines, and the quality of the evidence was evaluated using the GRADE tool. Inverse variance random-effects meta-analyses of standardized mean differences (SMD) and 95% confidence intervals (CIs) were calculated using RevMan 5.3 software. 53 RCTs with 4796 patients were finally included in the meta-analysis. The toothpastes that contain active desensitization ingredients showed a better desensitizing effect on DH than the negative control, except the strontium- and amorphous calcium phosphate-containing toothpastes. The amorphous calcium phosphate-containing toothpaste had very low-quality evidence, the strontium, potassium and strontium, and potassium and stannous fluoride-containing toothpastes had low-quality evidence, and the other five toothpastes had moderate quality evidence. Our result support the premise that toothpastes containing potassium, stannous fluoride, potassium and strontium, potassium and stannous fluoride, calcium sodium phosphosilicate, arginine, and nano-hydroxyapatite relieve the symptoms of DH, but does not advise the use of toothpastes that contain strontium and amorphous calcium phosphate. Furthermore, high-quality studies are needed to confirm our results. (PROSPERO CRD42018085639). Copyright © 2018 Elsevier Ltd. All rights reserved.

Generalized Constitutive-Based Theoretical and Empirical Models for Hot Working Behavior of Functionally Graded Steels

NASA Astrophysics Data System (ADS)

Vanini, Seyed Ali Sadough; Abolghasemzadeh, Mohammad; Assadi, Abbas

2013-07-01

Functionally graded steels with graded ferritic and austenitic regions including bainite and martensite intermediate layers produced by electroslag remelting have attracted much attention in recent years. In this article, an empirical model based on the Zener-Hollomon (Z-H) constitutive equation with generalized material constants is presented to investigate the effects of temperature and strain rate on the hot working behavior of functionally graded steels. Next, a theoretical model, generalized by strain compensation, is developed for the flow stress estimation of functionally graded steels under hot compression based on the phase mixture rule and boundary layer characteristics. The model is used for different strains and grading configurations. Specifically, the results for αβγMγ steels from empirical and theoretical models showed excellent agreement with those of experiments of other references within acceptable error.

Mineral resource of the month: fluorspar

USGS Publications Warehouse

,

2010-01-01

The article features the industrial mineral fluorspar, used in the manufacture of fluorochemicals, aluminum and steel. It defines fluorspar as crude or beneficiated material, mined or milled for the non-metallic mineral fluorite or calcium fluoride. Applications of acid-grade fluorspar in the U.S. are presented, including production of hydrofluoric acid for chemical production of refrigerants such as chlorofluorocarbons or CFCs. World demand for fluorspar decreased with the CFC ban in the 1990s, but recovered with the use of hydrofluorocarbons or HFCs.

Local calcium signalling is mediated by mechanosensitive ion channels in mesenchymal stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chubinskiy-Nadezhdin, Vladislav I., E-mail: vchubinskiy@gmail.com; Vasileva, Valeria Y.; Pugovkina, Natalia A.

Mechanical forces are implicated in key physiological processes in stem cells, including proliferation, differentiation and lineage switching. To date, there is an evident lack of understanding of how external mechanical cues are coupled with calcium signalling in stem cells. Mechanical reactions are of particular interest in adult mesenchymal stem cells because of their promising potential for use in tissue remodelling and clinical therapy. Here, single channel patch-clamp technique was employed to search for cation channels involved in mechanosensitivity in mesenchymal endometrial-derived stem cells (hMESCs). Functional expression of native mechanosensitive stretch-activated channels (SACs) and calcium-sensitive potassium channels of different conductances inmore » hMESCs was shown. Single current analysis of stretch-induced channel activity revealed functional coupling of SACs and BK channels in plasma membrane. The combination of cell-attached and inside-out experiments have indicated that highly localized Ca{sup 2+} entry via SACs triggers BK channel activity. At the same time, SK channels are not coupled with SACs despite of high calcium sensitivity as compared to BK. Our data demonstrate novel mechanism controlling BK channel activity in native cells. We conclude that SACs and BK channels are clusterized in functional mechanosensitive domains in the plasma membrane of hMESCs. Co-clustering of ion channels may significantly contribute to mechano-dependent calcium signalling in stem cells. - Highlights: • Stretch-induced channel activity in human mesenchymal stem cells was analyzed. • Functional expression of SACs and Ca{sup 2+}-sensitive BK and SK channels was shown. • Local Ca{sup 2+} influx via stretch-activated channels triggers BK channel activity. • SK channels are not coupled with SACs despite higher sensitivity to [Ca{sup 2+}]{sub i}. • Functional clustering of SACs and BK channels in stem cell membrane is proposed.« less

Efficacy of a multi-component exercise programme and nutritional supplementation on musculoskeletal health in men treated with androgen deprivation therapy for prostate cancer (IMPACT): study protocol of a randomised controlled trial.

PubMed

Owen, Patrick J; Daly, Robin M; Livingston, Patricia M; Mundell, Niamh L; Dalla Via, Jack; Millar, Jeremy L; Fraser, Steve F

2017-10-03

Prostate cancer is the most commonly diagnosed cancer in men in developed countries. Androgen deprivation therapy (ADT) is a systemic treatment shown to increase survival in selected patients with prostate cancer. The use of ADT continues to increase for all stages and grades of prostate cancer despite known treatment-induced adverse effects. The primary aim of this study is to examine the efficacy of a targeted, multi-component resistance and impact-loading exercise programme together with a daily protein-, calcium- and vitamin D-enriched supplement on bone health in men treated with ADT for prostate cancer. Secondary aims are to determine the effects of this intervention on measures of total body and regional body composition, cardiometabolic risk, inflammatory markers, health-related quality of life and cognitive function. This study is a two-arm randomised controlled trial. Men currently treated with ADT for prostate cancer will be randomised to either a 52-week, community-based, exercise training and nutritional supplementation intervention (n = 51) or usual care control (n = 51). Participants will be assessed at baseline, 26 weeks and 52 weeks for all measures. The primary outcome measures are proximal femur and lumbar spine areal bone mineral density (BMD). Secondary outcomes comprise: changes in tibial and radial bone structure and strength, total body and regional body composition, muscle strength and function, as well as cardiometabolic health, catabolic/inflammatory and anabolic/anti-inflammatory cytokines, health-related quality of life and cognitive function. This study investigates whether a multi-component intervention incorporating a targeted bone and muscle-loading programme in combination with a protein-, calcium- and vitamin D-enriched supplement can ameliorate multiple adverse effects of ADT when compared to usual care. The results will contribute to the development of exercise training and nutrition guidelines for optimising overall health in men treated with ADT for prostate cancer. Australia New Zealand Clinical Trial Registry (ANZCTR), ID: ACTRN12614000317695 . Registered on 25 march 2014.

Mixed-mode oscillations in a three-store calcium dynamics model

NASA Astrophysics Data System (ADS)

Liu, Peng; Liu, Xijun; Yu, Pei

2017-11-01

Calcium ions are important in cell process, which control cell functions. Many models on calcium oscillation have been proposed. Most of existing literature analyzed calcium oscillations using numerical methods, and found rich dynamical behaviours. In this paper, we explore a further study on an established three-store model, which contains endoplasmic reticulum (ER), mitochondria and calcium binding proteins. We conduct bifurcation analysis to identify two Hopf bifurcations, and apply normal form theory to study their stability and show that one of them is supercritical while the other is subcritical. Further, we transform the model into a slow-fast system, and then apply the geometrical singular perturbation theory to investigate the mechanism of generating slow-fast motions. The study reveals that the mechanism of generating the slow-fast oscillating behaviour in the three-store calcium model for certain parameter values is due to the relative fast change in the free calcium in cytosol, and relative slow changes in the free calcium in mitochondria and in the bounded Ca2+ binding sites on the cytosolic proteins. A further parametric study may provide some useful information for controlling harmful effect, by adjusting the amount of calcium in a human body. Numerical simulations are present to demonstrate the correct analytical predictions.

Hydrogen peroxide homeostasis: activation of plant catalase by calcium/calmodulin

NASA Technical Reports Server (NTRS)

Yang, T.; Poovaiah, B. W.

2002-01-01

Environmental stimuli such as UV, pathogen attack, and gravity can induce rapid changes in hydrogen peroxide (H(2)O(2)) levels, leading to a variety of physiological responses in plants. Catalase, which is involved in the degradation of H(2)O(2) into water and oxygen, is the major H(2)O(2)-scavenging enzyme in all aerobic organisms. A close interaction exists between intracellular H(2)O(2) and cytosolic calcium in response to biotic and abiotic stresses. Studies indicate that an increase in cytosolic calcium boosts the generation of H(2)O(2). Here we report that calmodulin (CaM), a ubiquitous calcium-binding protein, binds to and activates some plant catalases in the presence of calcium, but calcium/CaM does not have any effect on bacterial, fungal, bovine, or human catalase. These results document that calcium/CaM can down-regulate H(2)O(2) levels in plants by stimulating the catalytic activity of plant catalase. Furthermore, these results provide evidence indicating that calcium has dual functions in regulating H(2)O(2) homeostasis, which in turn influences redox signaling in response to environmental signals in plants.

Bioactive Polymeric Nanoparticles for Periodontal Therapy

PubMed Central

Alfonso-Rodríguez, Camilo Andrés; Medina-Castillo, Antonio L.; Alaminos, Miguel; Toledano, Manuel

2016-01-01

Aims to design calcium and zinc-loaded bioactive and cytocompatible nanoparticles for the treatment of periodontal disease. Methods PolymP-nActive nanoparticles were zinc or calcium loaded. Biomimetic calcium phosphate precipitation on polymeric particles was assessed after 7 days immersion in simulated body fluid, by scanning electron microscopy attached to an energy dispersive analysis system. Amorphous mineral deposition was probed by X-ray diffraction. Cell viability analysis was performed using oral mucosa fibroblasts by: 1) quantifying the liberated deoxyribonucleic acid from dead cells, 2) detecting the amount of lactate dehydrogenase enzyme released by cells with damaged membranes, and 3) by examining the cytoplasmic esterase function and cell membranes integrity with a fluorescence-based method using the Live/Dead commercial kit. Data were analyzed by Kruskal-Wallis and Mann-Whitney tests. Results Precipitation of calcium and phosphate on the nanoparticles surfaces was observed in calcium-loaded nanoparticles. Non-loaded nanoparticles were found to be non-toxic in all the assays, calcium and zinc-loaded particles presented a dose dependent but very low cytotoxic effect. Conclusions The ability of calcium-loaded nanoparticles to promote precipitation of calcium phosphate deposits, together with their observed non-toxicity may offer new strategies for periodontal disease treatment. PMID:27820866

Anthropogenic calcium depletion: a unique threat to forest ecosystem health?

Treesearch

Paul G. Schaberg; Donald H. DeHayes; Gary J. Hawley

2001-01-01

Numerous anthropogenic factors can deplete calcium (Ca) from forest ecosystems. Because an adequate supply of Ca is needed to support fundamental biological functions, including cell membrane stability and stress response, the potential for Ca deficiency following the individual, cumulative, or potentially synergistic, influences of anthropogenic factors raises...

ROLE OF HCL IN ADSORPTION OF ELEMENTAL MERCURY VAPOR BY CALCIUM-BASED SORBENTS

EPA Science Inventory

The paper gives results of a study to identify active sites and surface functional groups that may contribute to the adsorption of elemental mercury (Hg?) by relatively inexpensive calcium (Ca)-based sorbents. (NOTE: Hg? capture has been mostly investigated using high-surface-ar...

Chick cerebellar Purkinje cells express omega-conotoxin GVIA-sensitive rather than funnel-web spider toxin-sensitive calcium channels.

PubMed

Angulo, M C; Parra, P; Dieudonné, S

1998-03-01

Voltage-gated calcium channels form a complex family of distinct molecular entities which participate in multiple neuronal functions. In cerebellar Purkinje cells these channels contribute to the characteristic electrophysiological pattern of complex spikes, first described in birds and later in mammals. A specific calcium channel, the P-type channel, has been shown to mediate the majority of the voltage-gated calcium flux in mammalian Purkinje cells. P-type channels play an essential role in synaptic transmission of mammalian cerebellum. It is unclear whether the P-type calcium channel is present in birds. Studies in chick synaptosomal preparations show that the pharmacological profile of calcium channels is complex and suggest a minimal expression of the P-type channel in avian central nervous system. In the present work, we studied voltage-gated calcium channels in dissociated chick cerebellar Purkinje cells to examine the presence of different calcium channel types. Purkinje cells were used because, in mammals, they express predominantly P-type channels and because the morphology of these cells is thought to be phylogenetically conserved. We found that omega-conotoxin GVIA (omega-CgTx GVIA), a specific antagonist of N-type calcium channel, rather than the synthetic funnel-web spider toxin (sFTX), a P-type channel antagonist, blocks the majority of the barium current flowing through calcium channels in chick Purkinje neurons.

One Dimensional Finite Element Method Approach to Study Effect of Ryanodine Receptor and Serca Pump on Calcium Distribution in Oocytes

NASA Astrophysics Data System (ADS)

Naik, Parvaiz Ahmad; Pardasani, Kamal Raj

2013-11-01

Oocyte is a female gametocyte or germ cell involved in reproduction. Calcium ions (Ca2+) impact nearly all aspects of cellular life as they play an important role in a variety of cellular functions. Calcium ions contributes to egg activation upon fertilization. Since it is the internal stores which provide most of the calcium signal, much attention has been focused on the intracellular channels. There are mainly two types of calcium channels which release calcium from the internal stores to the cytoplasm in many cell types. These channels are IP3-Receptor and Ryanodine Receptor (RyR). Further it is essential to maintain low cytosolic calcium concentration, the cell engages the Serco/Endoplasmic reticulum Ca2+ ATPases (SERCA) present on the ER or SR membrane for the re-uptake of cytosolic calcium at the expense of ATP hydrolysis. In view of above an attempt has been made to study the effect of the Ryanodine receptor (RyR) and the SERCA pump on the calcium distribution in oocytes. The main aim of this paper is to study the calcium concentration in absence and presence of these parameters. The FEM is used to solve the proposed Mathematical model under appreciate initial and boundary conditions. The program has been developed in MATLAB 7.10 for the entire problem to get numerical results.

Correlation of Salivary Statherin and Calcium Levels with Dental Calculus Formation: A Preliminary Study.

PubMed

Pateel, Deepak Gowda Sadashivappa; Gunjal, Shilpa; Math, Swarna Y; Murugeshappa, Devarasa Giriyapura; Nair, Sreejith Muraleedharan

2017-01-01

Salivary constituents have a wide range of functions including oral calcium homeostasis. Salivary proteins such as statherin inhibit crystal growth of calcium phosphate in supersaturated solutions and interact with several oral bacteria to adsorb on hydroxyapatite. Concurrently, saliva, which is supersaturated with respect to calcium phosphates, is the driving force for plaque mineralization and formation of calculus. Thus, the aim of the present study was to estimate and correlate salivary statherin and calcium concentration to the dental calculus formation. A cross-sectional study was conducted to assess the relationship between salivary statherin, calcium, and dental calculus among 70 subjects, aged 20-55 years. Subjects were divided into 3 groups based on the calculus scores as interpreted by Calculus Index which was followed by collection of whole saliva using Super•SAL™. Salivary calcium levels were assessed by calorimetric method using Calcium Assay kit (Cayman Chemical, Michigan, USA) and statherin levels by using ELISA Kit (Cusabio Biotech). Statherin levels showed a weak negative correlation with the calcium levels and with calculus formation. The mean salivary statherin and calcium concentration were found to be 0.96  μ g/ml and 3.87 mg/ml, respectively. Salivary statherin levels differed significantly among the three groups ( p < 0.05). Our preliminary data indicates that statherin could possibly play a role in the formation of dental calculus.

Two Dimensional Finite Element Model to Study Calcium Distribution in Oocytes

NASA Astrophysics Data System (ADS)

Naik, Parvaiz Ahmad; Pardasani, Kamal Raj

2015-06-01

Cytosolic free calcium concentration is a key regulatory factor and perhaps the most widely used means of controlling cellular function. Calcium can enter cells through different pathways which are activated by specific stimuli including membrane depolarization, chemical signals and calcium depletion of intracellular stores. One of the important components of oocyte maturation is differentiation of the Ca2+ signaling machinery which is essential for egg activation after fertilization. Eggs acquire the ability to produce the fertilization-specific calcium signal during oocyte maturation. The calcium concentration patterns required during different stages of oocyte maturation are still not completely known. Also the mechanisms involved in calcium dynamics in oocyte cell are still not well understood. In view of above a two dimensional FEM model has been proposed to study calcium distribution in an oocyte cell. The parameters such as buffers, ryanodine receptor, SERCA pump and voltage gated calcium channel are incorporated in the model. Based on the biophysical conditions the initial and boundary conditions have been framed. The model is transformed into variational form and Ritz finite element method has been employed to obtain the solution. A program has been developed in MATLAB 7.10 for the entire problem and executed to obtain numerical results. The numerical results have been used to study the effect of buffers, RyR, SERCA pump and VGCC on calcium distribution in an oocyte cell.

Local Control Models of Cardiac Excitation–Contraction Coupling

PubMed Central

Stern, Michael D.; Song, Long-Sheng; Cheng, Heping; Sham, James S.K.; Yang, Huang Tian; Boheler, Kenneth R.; Ríos, Eduardo

1999-01-01

In cardiac muscle, release of activator calcium from the sarcoplasmic reticulum occurs by calcium- induced calcium release through ryanodine receptors (RyRs), which are clustered in a dense, regular, two-dimensional lattice array at the diad junction. We simulated numerically the stochastic dynamics of RyRs and L-type sarcolemmal calcium channels interacting via calcium nano-domains in the junctional cleft. Four putative RyR gating schemes based on single-channel measurements in lipid bilayers all failed to give stable excitation–contraction coupling, due either to insufficiently strong inactivation to terminate locally regenerative calcium-induced calcium release or insufficient cooperativity to discriminate against RyR activation by background calcium. If the ryanodine receptor was represented, instead, by a phenomenological four-state gating scheme, with channel opening resulting from simultaneous binding of two Ca2+ ions, and either calcium-dependent or activation-linked inactivation, the simulations gave a good semiquantitative accounting for the macroscopic features of excitation–contraction coupling. It was possible to restore stability to a model based on a bilayer-derived gating scheme, by introducing allosteric interactions between nearest-neighbor RyRs so as to stabilize the inactivated state and produce cooperativity among calcium binding sites on different RyRs. Such allosteric coupling between RyRs may be a function of the foot process and lattice array, explaining their conservation during evolution. PMID:10051521

The Contribution of Executive Functions to Narrative Writing in Fourth Grade Children

ERIC Educational Resources Information Center

Drijbooms, Elise; Groen, Margriet A.; Verhoeven, Ludo

2015-01-01

The present study investigated the contribution of executive functions to narrative writing in fourth grade children, and evaluated to what extent executive functions contribute differentially to different levels of narrative composition. The written skills of 102 Dutch children in fourth grade were assessed using a narrative picture-elicitation…

S100A7 promotes the migration, invasion and metastasis of human cervical cancer cells through epithelial–mesenchymal transition

PubMed Central

Ma, Jianlin; Wu, Xiaowei; Liu, Zhihua; Chen, Hongyan; Cui, Zhumei

2017-01-01

S100A7 is an EF-hand calcium-binding protein that has been suggested to be implicated in cell proliferation, migration, invasion and tumor metastasis. However, its role in cervical cancer has not yet been fully clarified. The present study used immunohistochemistry analysis of S100A7 in clinical specimens of cervical cancer to show that S100A7 expression was significantly upregulated in cervical cancer tissues compared with normal cervical tissues and S100A7 expression in high grade cervical intraepithelial neoplasm (CIN) was significantly higher than cervical cancer. Statistical analysis showed that S100A7 expression was associated with tumor grade (P <0.01) and lymph node metastasis (P <0.05). Functional studies showed that overexpression of S100A7 in cervical cancer cells promoted migration, invasion and metastasis of cervical cancer cells without influencing cell proliferation. Furthermore, S100A7 was found to be secreted into the conditioned media and extracellular S100A7 enhanced cell migration and invasion. Mechanistically, S100A7 bound to RAGE and activated ERK signaling pathway. And S100A7 enhanced cell mesenchymal properties and induced epithelial–mesenchymal transition. In summary, these data reveal a crucial role for S100A7 in regulating cell migration, invasion, metastasis and EMT of cervical cancer and suggest that targeting S100A7 may offer a new targeted strategy for cervical cancer. PMID:28212564

S100A7 promotes the migration, invasion and metastasis of human cervical cancer cells through epithelial-mesenchymal transition.

PubMed

Tian, Tian; Li, Xukun; Hua, Zhen; Ma, Jianlin; Wu, Xiaowei; Liu, Zhihua; Chen, Hongyan; Cui, Zhumei

2017-04-11

S100A7 is an EF-hand calcium-binding protein that has been suggested to be implicated in cell proliferation, migration, invasion and tumor metastasis. However, its role in cervical cancer has not yet been fully clarified. The present study used immunohistochemistry analysis of S100A7 in clinical specimens of cervical cancer to show that S100A7 expression was significantly upregulated in cervical cancer tissues compared with normal cervical tissues and S100A7 expression in high grade cervical intraepithelial neoplasm (CIN) was significantly higher than cervical cancer. Statistical analysis showed that S100A7 expression was associated with tumor grade (P <0.01) and lymph node metastasis (P <0.05). Functional studies showed that overexpression of S100A7 in cervical cancer cells promoted migration, invasion and metastasis of cervical cancer cells without influencing cell proliferation. Furthermore, S100A7 was found to be secreted into the conditioned media and extracellular S100A7 enhanced cell migration and invasion. Mechanistically, S100A7 bound to RAGE and activated ERK signaling pathway. And S100A7 enhanced cell mesenchymal properties and induced epithelial-mesenchymal transition. In summary, these data reveal a crucial role for S100A7 in regulating cell migration, invasion, metastasis and EMT of cervical cancer and suggest that targeting S100A7 may offer a new targeted strategy for cervical cancer.

Calcium dynamics in cardiac excitatory and non-excitatory cells and the role of gap junction.

PubMed

Das, Phonindra Nath; Mehrotra, Parul; Mishra, Aseem; Bairagi, Nandadulal; Chatterjee, Samrat

2017-07-01

Calcium ions aid in the generation of action potential in myocytes and are responsible for the excitation-contraction coupling of heart. The heart muscle has specialized patches of cells, called excitatory cells (EC) such as the Sino-atrial node cells capable of auto-generation of action potential and cells which receive signals from the excitatory cells, called non-excitatory cells (NEC) such as cells of the ventricular and auricular walls. In order to understand cardiac calcium homeostasis, it is, therefore, important to study the calcium dynamics taking into account both types of cardiac cells. Here we have developed a model to capture the calcium dynamics in excitatory and non-excitatory cells taking into consideration the gap junction mediated calcium ion transfer from excitatory cell to non-excitatory cell. Our study revealed that the gap junctional coupling between excitatory and non-excitatory cells plays important role in the calcium dynamics. It is observed that any reduction in the functioning of gap junction may result in abnormal calcium oscillations in NEC, even when the calcium dynamics is normal in EC cell. Sensitivity of gap junction is observed to be independent of the pacing rate and hence a careful monitoring is required to maintain normal cardiomyocyte condition. It also highlights that sarcoplasmic reticulum may not be always able to control the amount of cytoplasmic calcium under the condition of calcium overload. Copyright © 2017 Elsevier Inc. All rights reserved.

Recovery of valuable elements from spent Li-batteries.

PubMed

Paulino, Jéssica Frontino; Busnardo, Natália Giovanini; Afonso, Julio Carlos

2008-02-11

This work examines two recycling processes for spent Li/MnO(2) and Li-ion batteries. The anode, cathode and electrolyte (LiPF(6)) were submitted to one of the following procedures: (a) calcination at 500 degrees C (5h) followed by solvent extraction to recover lithium salts (fluoride, phosphate) in good yield (90 wt%). The residual solid was treated with H(2)SO(4) containing H(2)O(2) and on evaporation gave high purity grade cobalt or manganese sulfate; (b) fusion with KHSO(4) (500 degrees C, 5h). The resulting aqueous solution was added dropwise to a solution of NaOH, giving cobalt or manganese as impure precipitate. Addition of KF precipitated high purity grade LiF in moderate yield (50 wt%). The final aqueous solution on treatment with calcium sulfate precipitated the corresponding phosphate and fluoride salts.

Assessment of Liver Function in Patients With Hepatocellular Carcinoma: A New Evidence-Based Approach—The ALBI Grade

PubMed Central

Johnson, Philip J.; Berhane, Sarah; Kagebayashi, Chiaki; Satomura, Shinji; Teng, Mabel; Reeves, Helen L.; O'Beirne, James; Fox, Richard; Skowronska, Anna; Palmer, Daniel; Yeo, Winnie; Mo, Frankie; Lai, Paul; Iñarrairaegui, Mercedes; Chan, Stephen L.; Sangro, Bruno; Miksad, Rebecca; Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori

2015-01-01

Purpose Most patients with hepatocellular carcinoma (HCC) have associated chronic liver disease, the severity of which is currently assessed by the Child-Pugh (C-P) grade. In this international collaboration, we identify objective measures of liver function/dysfunction that independently influence survival in patients with HCC and then combine these into a model that could be compared with the conventional C-P grade. Patients and Methods We developed a simple model to assess liver function, based on 1,313 patients with HCC of all stages from Japan, that involved only serum bilirubin and albumin levels. We then tested the model using similar cohorts from other geographical regions (n = 5,097) and other clinical situations (patients undergoing resection [n = 525] or sorafenib treatment for advanced HCC [n = 1,132]). The specificity of the model for liver (dys)function was tested in patients with chronic liver disease but without HCC (n = 501). Results The model, the Albumin-Bilirubin (ALBI) grade, performed at least as well as the C-P grade in all geographic regions. The majority of patients with HCC had C-P grade A disease at presentation, and within this C-P grade, ALBI revealed two classes with clearly different prognoses. Its utility in patients with chronic liver disease alone supported the contention that the ALBI grade was indeed an index of liver (dys)function. Conclusion The ALBI grade offers a simple, evidence-based, objective, and discriminatory method of assessing liver function in HCC that has been extensively tested in an international setting. This new model eliminates the need for subjective variables such as ascites and encephalopathy, a requirement in the conventional C-P grade. PMID:25512453

Transgenic Analysis of the Role of FKBP12.6 in Cardiac Function and Intracellular Calcium Release

PubMed Central

Liu, Ying; Chen, Hanying; Ji, Guangju; Li, Baiyan; Mohler, Peter J.; Zhu, Zhiming; Yong, Weidong; Chen, Zhuang; Xu, Xuehong

2011-01-01

Abstract FK506 binding protein12.6 (FKBP12.6) binds to the Ca2+ release channel ryanodine receptor (RyR2) in cardiomyocytes and stabilizes RyR2 to prevent premature sarcoplasmic reticulum Ca2+ release. Previously, two different mouse strains deficient in FKBP12.6 were reported to have different abnormal cardiac phenotypes. The first mutant strain displayed sex-dependent cardiac hypertrophy, while the second displayed exercise-induced cardiac arrhythmia and sudden death. In this study, we tested whether FKBP12.6-deficient mice that display hypertrophic hearts can develop exercise-induced cardiac sudden death and whether the hypertrophic heart is a direct consequence of abnormal calcium handling in mutant cardiomyocytes. Our data show that FKBP12.6-deficient mice with cardiac hypertrophy do not display exercise-induced arrhythmia and/or sudden cardiac death. To investigate the role of FKBP12.6 overexpression for cardiac function and cardiomyocyte calcium release, we generated a transgenic mouse line with cardiac specific overexpression of FKBP12.6 using α-myosin heavy chain (αMHC) promoter. MHC-FKBP12.6 mice displayed normal cardiac development and function. We demonstrated that MHC-FKBP12.6 mice are able to rescue abnormal cardiac hypertrophy and abnormal calcium release in FKBP12.6-deficient mice. PMID:22087651

Store-Operated Calcium Channels

PubMed Central

Lewis, Richard S.

2015-01-01

Store-operated calcium channels (SOCs) are a major pathway for calcium signaling in virtually all metozoan cells and serve a wide variety of functions ranging from gene expression, motility, and secretion to tissue and organ development and the immune response. SOCs are activated by the depletion of Ca2+ from the endoplasmic reticulum (ER), triggered physiologically through stimulation of a diverse set of surface receptors. Over 15 years after the first characterization of SOCs through electrophysiology, the identification of the STIM proteins as ER Ca2+ sensors and the Orai proteins as store-operated channels has enabled rapid progress in understanding the unique mechanism of store-operate calcium entry (SOCE). Depletion of Ca2+ from the ER causes STIM to accumulate at ER-plasma membrane (PM) junctions where it traps and activates Orai channels diffusing in the closely apposed PM. Mutagenesis studies combined with recent structural insights about STIM and Orai proteins are now beginning to reveal the molecular underpinnings of these choreographic events. This review describes the major experimental advances underlying our current understanding of how ER Ca2+ depletion is coupled to the activation of SOCs. Particular emphasis is placed on the molecular mechanisms of STIM and Orai activation, Orai channel properties, modulation of STIM and Orai function, pharmacological inhibitors of SOCE, and the functions of STIM and Orai in physiology and disease. PMID:26400989

Vitamin D: a hormone for all seasons.

PubMed

Mason, R S

2011-04-01

Vitamin D is principally obtained from skin through the action of ultraviolet B irradiation on 7-dehydrocholesterol. It is further metabolized to 25-hydroxyvitamin D, the major circulating vitamin D compound, and then to 1,25-dihydroxyvitamin D, the hormonal form. The major function of vitamin D compounds is to enhance active absorption of calcium (and phosphate) from the gut, ensuring that bone does not need to be resorbed to maintain blood calcium concentrations despite obligatory urinary losses. Vitamin D compounds have direct effects to enhance bone and muscle function. Based on good evidence, target levels for 25-hydroxyvitamin D in blood are at least 50 nmol/l and there may be a case for higher targets of 75-80 nmol/l. Adequate calcium intakes help to reduce vitamin D degradation. Vitamin D and calcium together reduce the risk of falls and fractures in older people. There are vitamin D receptors in most nucleated cells and preliminary evidence that adequate vitamin D levels may be important in reducing the incidence of, or mortality from, some cancers, and in reducing autoimmune disease. Adequate vitamin D may also allow for a normal innate immune response to pathogens, improve cardiovascular function and mortality, and reduce type 2 diabetes. Supplemental vitamin D seems to work in a generally similar manner to skin-derived vitamin D.

Novel botanical drug DA-9803 prevents deficits in Alzheimer's mouse models.

PubMed

Pagnier, Guillaume J; Kastanenka, Ksenia V; Sohn, Miwon; Choi, Sangzin; Choi, Song-Hyen; Soh, HyeYeon; Bacskai, Brian J

2018-01-29

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by deposition of amyloid plaques and disruption of neural circuitry, leading to cognitive decline. Animal models of AD deposit senile plaques and exhibit structural and functional deficits in neurons and neural networks. An effective treatment would prevent or restore these deficits, including calcium dyshomeostasis observed with in-vivo imaging. We examined the effects of DA-9803, a multimodal botanical drug, in 5XFAD and APP/PS1 transgenic mice which underwent daily oral treatment with 30 or 100 mg/kg DA-9803 or vehicle alone. Behavioral testing and longitudinal imaging of amyloid deposits and intracellular calcium in neurons with multiphoton microscopy was performed. Chronic administration of DA-9803 restored behavioral deficits in 5XFAD mice and reduced amyloid-β levels. DA-9803 also prevented progressive amyloid plaque deposition in APP/PS1 mice. Elevated calcium, detected in a subset of neurons before the treatment, was restored and served as a functional indicator of treatment efficacy in addition to the behavioral readout. In contrast, mice treated with vehicle alone continued to progressively accumulate amyloid plaques and calcium overload. In summary, treatment with DA-9803 prevented structural and functional outcome measures in mouse models of AD. Thus, DA-9803 shows promise as a novel therapeutic approach for Alzheimer's disease.

Ubiquitylation Functions in the Calcium Carbonate Biomineralization in the Extracellular Matrix

PubMed Central

Fang, Dong; Pan, Cong; Lin, Huijuan; Lin, Ya; Xu, Guangrui; Zhang, Guiyou; Wang, Hongzhong; Xie, Liping; Zhang, Rongqing

2012-01-01

Mollusks shell formation is mediated by matrix proteins and many of these proteins have been identified and characterized. However, the mechanisms of protein control remain unknown. Here, we report the ubiquitylation of matrix proteins in the prismatic layer of the pearl oyster, Pinctada fucata. The presence of ubiquitylated proteins in the prismatic layer of the shell was detected with a combination of western blot and immunogold assays. The coupled ubiquitins were separated and identified by Edman degradation and liquid chromatography/mass spectrometry (LC/MS). Antibody injection in vivo resulted in large amounts of calcium carbonate randomly accumulating on the surface of the nacreous layer. These ubiquitylated proteins could bind to specific faces of calcite and aragonite, which are the two main mineral components of the shell. In the in vitro calcium carbonate crystallization assay, they could reduce the rate of calcium carbonate precipitation and induce the calcite formation. Furthermore, when the attached ubiquitins were removed, the functions of the EDTA-soluble matrix of the prismatic layer were changed. Their potency to inhibit precipitation of calcium carbonate was decreased and their influence on the morphology of calcium carbonate crystals was changed. Taken together, ubiquitylation is involved in shell formation. Although the ubiquitylation is supposed to be involved in every aspect of biophysical processes, our work connected the biomineralization-related proteins and the ubiquitylation mechanism in the extracellular matrix for the first time. This would promote our understanding of the shell biomineralization and the ubiquitylation processes. PMID:22558208

Using MRI to detect and differentiate calcium oxalate and calcium hydroxyapatite crystals in air-bubble-free phantom

PubMed Central

Mustafi, Devkumar; Fan, Xiaobing; Peng, Bo; Foxley, Sean; Palgen, Jeremy; Newstead, Gillian M.

2015-01-01

Calcium oxalate (CaOX) crystals and calcium hydroxyapatite (CaHA) crystals were commonly associated with breast benign and malignant lesions, respectively. In this research, CaOX (n = 6) and CaHA (n = 6) crystals in air-bubble-free agarose phantom were studied and characterized by using MRI at 9.4 Tesla scanner. Calcium micro-crystals sizes ranged from 200 – 500 microns were made with either 99% pure CaOX or CaHA powder and embedded in agar to mimic the dimensions and calcium content of breast microcalcifications in vivo. MRI data were acquired with high spatial resolution T2-weighted (T2W) images and gradient echo images with five different echo times (TEs). The crystals areas were determined by setting the threshold relative to agarose signal. The ratio of crystals areas were calculated by the measurements from gradient echo images divided by T2W images. Then the ratios as a function of TE were fitted with the radical function. The results showed that the blooming artifacts due to magnetic susceptibility between agar and CaHA crystals were more than twice as large as the susceptibility in CaOX crystals (p < 0.05). In addition, larger bright rings were observed on gradient echo images around CaHA crystals compared to CaOX crystals. Our results suggest that MRI may provide useful information regarding breast microcalcifications by evaluating the apparent area of crystals ratios obtained between gradient echo and T2W images. PMID:26392170

Multi-modal in vivo imaging of brain blood oxygenation, blood flow and neural calcium dynamics during acute seizures

NASA Astrophysics Data System (ADS)

Ringuette, Dene; Jeffrey, Melanie A.; Carlen, Peter L.; Levi, Ofer

2016-03-01

Dysfunction of the vascular endothelium has been implicated in the development of epilepsy. To better understand the relation between vascular function and seizure and provide a foundation for interpreting results from functional imaging in chronic disease models, we investigate the relationship between intracellular calcium dynamics and local cerebral blood flow and blood oxygen saturation during acute seizure-like events and pharmacological seizure rescue. To probe the relation between the aforementioned physiological markers in an acute model of epilepsy in rats, we integrated three different optical modalities together with electrophysiological recordings: Laser speckle contrast imaging (LSCI) was used to study changes in flow speeds, Intrinsic optical signal imaging (IOSI) was used to monitor changes in oxygenated, de-oxygenated, and total hemoglobin concentration, and Calcium-sensitive dye imaging was used to monitor intracellular calcium dynamics. We designed a dedicated cortical flow chamber to remove superficial blood and dye resulting from the injection procedure, which reduced spurious artifacts. The near infrared light used for IOSI and LSCI was delivered via a light pipe integrated with the flow chamber to minimize the effect of fluid surface movement on illumination stability. Calcium-sensitive dye was injected via a glass electrode used for recording the local field potential. Our system allowed us to observe and correlate increases in intracellular calcium, blood flow and blood volume during seizure-like events and provide a quantitative analysis of neurovascular coupling changes associated with seizure rescue via injection of an anti-convulsive agent.

The Charge-Balancing Role of Calcium and Alkali Ions in Per-Alkaline Aluminosilicate Glasses.

PubMed

Thomsen, René M; Skibsted, Jørgen; Yue, Yuanzheng

2018-03-29

The structural arrangement of alkali-modified calcium aluminosilicate glasses has implications for important properties of these glasses in a wide range of industrial applications. The roles of sodium and potassium and their competition with calcium as network modifiers in peralkaline aluminosilicate glasses have been investigated by 27 Al and 29 Si MAS NMR spectroscopy. The 29 Si MAS NMR spectra are simulated using two models for distributing Al in the silicate glass network. One model assumes a hierarchical, quasi-heterogeneous aluminosilicate network, whereas the other is based on differences in relative lattice energies between Si-O-Si, Al-O-Al, and Si-O-Al linkages. A systematic divergence between these simulations and the experimental 29 Si NMR spectra is observed as a function of the sodium content exceeding that required for stoichiometric charge-balancing of the negatively charged AlO 4 tetrahedra. Similar correlations between simulations and experimental 29 Si NMR spectra cannot be made for the excess calcium content. Moreover, systematic variations in the 27 Al isotropic chemical shifts and the second-order quadrupole effect parameters, derived from the 27 Al MAS NMR spectra, are reported as a function of the SiO 2 content. These observations strongly suggest that alkali ions preferentially charge-balance AlO 4 3- as compared to alkaline earth (calcium) ions. In contrast, calcium dominates over the alkali ions in the formation of nonbridging oxygens associated with the SiO 4 tetrahedra.

Neuropeptide Secreted from a Pacemaker Activates Neurons to Control a Rhythmic Behavior

PubMed Central

Wang, Han; Girskis, Kelly; Janssen, Tom; Chan, Jason P.; Dasgupta, Krishnakali; Knowles, James A.; Schoofs, Liliane; Sieburth, Derek

2013-01-01

Summary Background Rhythmic behaviors are driven by endogenous biological clocks in pacemakers, which must reliably transmit timing information to target tissues that execute rhythmic outputs. During the defecation motor program in C. elegans, calcium oscillations in the pacemaker (intestine), which occur about every 50 seconds, trigger rhythmic enteric muscle contractions through downstream GABAergic neurons that innervate enteric muscles. However, the identity of the timing signal released by the pacemaker and the mechanism underlying the delivery of timing information to the GABAergic neurons are unknown. Results Here we show that a neuropeptide-like protein (NLP-40) released by the pacemaker triggers a single rapid calcium transient in the GABAergic neurons during each defecation cycle. We find that mutants lacking nlp-40 have normal pacemaker function, but lack enteric muscle contractions. NLP-40 undergoes calcium-dependent release that is mediated by the calcium sensor, SNT-2/synaptotagmin. We identify AEX-2, the G protein-coupled receptor on the GABAergic neurons, as the receptor of NLP-40. Functional calcium imaging reveals that NLP-40 and AEX-2/GPCR are both necessary for rhythmic activation of these neurons. Furthermore, acute application of synthetic NLP-40-derived peptide depolarizes the GABAergic neurons in vivo. Conclusions Our results show that NLP-40 carries the timing information from the pacemaker via calcium-dependent release and delivers it to the GABAergic neurons by instructing their activation. Thus, we propose that rhythmic release of neuropeptides can deliver temporal information from pacemakers to downstream neurons to execute rhythmic behaviors. PMID:23583549

Mice deficient in carbonic anhydrase type 8 exhibit motor dysfunctions and abnormal calcium dynamics in the somatic region of cerebellar granule cells.

PubMed

Lamont, Matthew G; Weber, John T

2015-06-01

The waddles (wdl) mouse is characterized by a namesake "side-to-side" waddling gait due to a homozygous mutation of the Car8 gene. This mutation results in non-functional copies of the protein carbonic anhydrase type 8. Rota-rod testing was conducted to characterize the wdl mutations' effect on motor output. Results indicated that younger homozygotes outperformed their older cohorts, an effect not seen in previous studies. Heterozygotes, which were thought to be free of motor impairment, displayed motor learning deficiencies when compared with wild type performance. Acute cerebellar slices were then utilized for fluorescent calcium imaging experiments, which revealed significant alterations in cerebellar granule cell somatic calcium signaling when exposed to glutamate. The contribution of GABAergic signaling to these alterations was also verified using bath application of bicuculline. Changes in somatic calcium signals were found to be applicable to an in vivo scenario by comparing group responses to electrical stimulation of afferent mossy fiber projections. Finally, intracellular calcium store function was also found to be altered by the wdl mutation when slices were treated with thapsigargin. These findings, taken together with previous work on the wdl mouse, indicate a widespread disruption in cerebellar circuitry hampering proper neuronal communication. Copyright © 2015 Elsevier B.V. All rights reserved.

Crystal structures of the GCaMP calcium sensor reveal the mechanism of fluorescence signal change and aid rational design.

PubMed

Akerboom, Jasper; Rivera, Jonathan D Vélez; Guilbe, María M Rodríguez; Malavé, Elisa C Alfaro; Hernandez, Hector H; Tian, Lin; Hires, S Andrew; Marvin, Jonathan S; Looger, Loren L; Schreiter, Eric R

2009-03-06

The genetically encoded calcium indicator GCaMP2 shows promise for neural network activity imaging, but is currently limited by low signal-to-noise ratio. We describe x-ray crystal structures as well as solution biophysical and spectroscopic characterization of GCaMP2 in the calcium-free dark state, and in two calcium-bound bright states: a monomeric form that dominates at intracellular concentrations observed during imaging experiments and an unexpected domain-swapped dimer with decreased fluorescence. This series of structures provides insight into the mechanism of Ca2+-induced fluorescence change. Upon calcium binding, the calmodulin (CaM) domain wraps around the M13 peptide, creating a new domain interface between CaM and the circularly permuted enhanced green fluorescent protein domain. Residues from CaM alter the chemical environment of the circularly permuted enhanced green fluorescent protein chromophore and, together with flexible inter-domain linkers, block solvent access to the chromophore. Guided by the crystal structures, we engineered a series of GCaMP2 point mutants to probe the mechanism of GCaMP2 function and characterized one mutant with significantly improved signal-to-noise. The mutation is located at a domain interface and its effect on sensor function could not have been predicted in the absence of structural data.

Effect of soluble calcium on the renneting properties of casein micelles as measured by rheology and diffusing wave spectroscopy.

PubMed

Sandra, S; Ho, M; Alexander, M; Corredig, M

2012-01-01

Addition of calcium chloride to milk has positive effects on cheese-making because it decreases coagulation time, creates firmer gels, and increases curd yield. Although addition of calcium chloride is a widely used industrial practice, the effect of soluble calcium on the preliminary stages of gelation is not fully understood. In addition, it is not known whether the manner of addition and equilibration of the soluble calcium would affect the rennetability of the casein micelles. Therefore, the aim of this paper was to study the details of the coagulation behavior of casein micelles in the presence of additional calcium, and to elucidate whether the manner in which this cation is added (directly as calcium chloride or by gradual exchange through dialysis) affects the functionality of the micelles. Calcium was added as CaCl(2) (1 mM final added concentration) directly to skim milk or indirectly using dialysis against 50 volumes of milk. Additional soluble calcium did not affect the primary phase of the renneting reaction, as demonstrated by the analysis of the casein macropeptide (CMP) released in solution; however, it shortened the coagulation time of the micelles and increased the firmness of the gel. The turbidity parameter of samples with or without calcium showed that similar amounts of CMP were needed for particle interactions to commence. However, the amount of CMP released at the point of gelation, as indicated by rheology, was lesser for samples with added calcium, which can be attributed to a greater extent of calcium bridging on the surface or between micelles. The results also showed that the manner in which calcium was presented to the micelles did not influence the mechanism of gelation. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Hydrostatic Pressure–Induced Release of Stored Calcium in Cultured Rat Optic Nerve Head Astrocytes

PubMed Central

Mandal, Amritlal; Delamere, Nicholas A.

2010-01-01

Purpose. Elevated intraocular pressure is associated with glaucomatous optic nerve damage. Other investigators have shown functional changes in optic nerve head astrocytes subjected to elevated hydrostatic pressure (HP) for 1 to 5 days. Recently, the authors reported ERK1/2, p90RSK and NHE1 phosphorylation after 2 hours. Here they examine calcium responses at the onset of HP to determine what precedes ERK1/2 phosphorylation. Methods. Cytoplasmic calcium concentration ([Ca2+]i) was measured in cultured rat optic nerve astrocytes loaded with fura-2. The cells were placed in a closed imaging chamber and subjected to an HP increase of 15 mm Hg. Protein phosphorylation was detected by Western blot analysis. Results. The increase of HP caused an immediate slow increase in [Ca2+]i. The response persisted in calcium-free solution and when nickel chloride (4 mM) was added to suppress channel-mediated calcium entry. Previous depletion of the ER calcium stores by cyclopiazonic acid abolished the HP-induced calcium level increase. The HP-induced increase persisted in cells exposed to xestospongin C, an inhibitor of IP3R-mediated calcium release. In contrast, ryanodine receptor (RyR) antagonist ruthenium red (10 μM) or dantrolene (25 μM) inhibited the HP-induced calcium increase. The HP-induced calcium increase was abolished when ryanodine-sensitive calcium stores were pre-depleted with caffeine (3 mM). HP caused ERK1/2 phosphorylation. The magnitude of the ERK1/2 phosphorylation response was reduced by ruthenium red and dantrolene. Conclusions. Increasing HP causes calcium release from a ryanodine-sensitive cytoplasmic store and subsequent ERK1/2 activation. Calcium store release appears to be a required early step in the initial astrocyte response to an HP increase. PMID:20071675

Genetic ablation of calcium-independent phospholipase A2gamma leads to alterations in mitochondrial lipid metabolism and function resulting in a deficient mitochondrial bioenergetic phenotype.

PubMed

Mancuso, David J; Sims, Harold F; Han, Xianlin; Jenkins, Christopher M; Guan, Shao Ping; Yang, Kui; Moon, Sung Ho; Pietka, Terri; Abumrad, Nada A; Schlesinger, Paul H; Gross, Richard W

2007-11-30

Previously, we identified a novel calcium-independent phospholipase, designated calcium-independent phospholipase A(2) gamma (iPLA(2)gamma), which possesses dual mitochondrial and peroxisomal subcellular localization signals. To identify the roles of iPLA(2)gamma in cellular bioenergetics, we generated mice null for the iPLA(2)gamma gene by eliminating the active site of the enzyme through homologous recombination. Mice null for iPLA(2)gamma display multiple bioenergetic dysfunctional phenotypes, including 1) growth retardation, 2) cold intolerance, 3) reduced exercise endurance, 4) greatly increased mortality from cardiac stress after transverse aortic constriction, 5) abnormal mitochondrial function with a 65% decrease in ascorbate-induced Complex IV-mediated oxygen consumption, and 6) a reduction in myocardial cardiolipin content accompanied by an altered cardiolipin molecular species composition. We conclude that iPLA(2)gamma is essential for maintaining efficient bioenergetic mitochondrial function through tailoring mitochondrial membrane lipid metabolism and composition.

Growth of aragonite calcium carbonate nanorods in the biomimetic anodic aluminum oxide template

NASA Astrophysics Data System (ADS)

Lee, Inho; Han, Haksoo; Lee, Sang-Yup

2010-04-01

In this study, a biomimetic template was prepared and applied for growing calcium carbonate (CaCO 3) nanorods whose shape and polymorphism were controlled. A biomimetic template was prepared by adsorbing catalytic dipeptides into the pores of an anodic aluminum oxide (AAO) membrane. Using this peptide-adsorbed template, mineralization and aggregation of CaCO 3 was carried out to form large nanorods in the pores. The nanorods were aragonite and had a structure similar to nanoneedle assembly. This aragonite nanorod formation was driven by both the AAO template and catalytic function of dipeptides. The AAO membrane pores promoted generation of aragonite polymorph and guided nanorod formation by guiding the nanorod growth. The catalytic dipeptides promoted the aggregation and further dehydration of calcium species to form large nanorods. Functions of the AAO template and catalytic dipeptides were verified through several control experiments. This biomimetic approach makes possible the production of functional inorganic materials with controlled shapes and crystalline structures.

The effect of calcium on the composition and physical properties of whey protein particles prepared using emulsification.

PubMed

Westerik, Nieke; Scholten, Elke; Corredig, Milena

2015-06-15

Protein microparticles were formed through emulsification of 25% (w/w) whey protein isolate (WPI) solutions containing various concentrations of calcium (0.0-400.0mM) in an oil phase stabilized by polyglycerol polyricinoleate (PGPR). The emulsions were heated (at 80°C) and the microparticles subsequently re-dispersed in an aqueous phase. Light microscopy and scanning electron microscopy (SEM) images revealed that control particles and those prepared with 7.4mM calcium were spherical and smooth. Particles prepared with 15.0mM calcium gained an irregular, cauliflower-like structure, and at concentrations larger than 30.0mM, shells formed and the particles were no longer spherical. These results describe, for the first time, the potential of modulating the properties of dense whey protein particles by using calcium, and may be used as structuring agents for the design of functional food matrices with increased protein and calcium content. Copyright © 2015. Published by Elsevier Ltd.

Physicochemical properties of nixtamalized corn flours with and without germ.

PubMed

Vega Rojas, Lineth J; Rojas Molina, Isela; Gutiérrez Cortez, Elsa; Rincón Londoño, Natalia; Acosta Osorio, Andrés A; Del Real López, Alicia; Rodríguez García, Mario E

2017-04-01

This research studied the influence of the germ components on the physicochemical properties of cooked corn and nixtamalized corn flours as a function of the calcium hydroxide content (from 0 to 2.1 w/w) and steeping time (between 0 and 9h). A linear relationship was found between calcium content in germ and steeping time used during nixtamalization process. X-ray diffraction analysis showed that calcium carbonate is formed into the germ structure to 2.1 w/w of calcium hydroxide and 9h steeping time. The presence of the germ improves the development of peak viscosity in flours, and it is related to the increases in calcium concentration in germ and the formation of amylose-lipid complexes. No significant changes were observed in palmitic, stearic, oleic and linoleic acids of corn oil. The levels of further corn oil deterioration were 2.1 w/w of calcium hydroxide concentration and 9h of steeping time. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ca K-Edge XAS as a Probe of Calcium Centers in Complex Systems

DOE PAGES

Martin-Diaconescu, Vlad; Gennari, Marcello; Gerey, Bertrand; ...

2014-12-10

Calcium K-edge pre-edges coupled with TD-DFT theoretical calculation of spectra provide a powerful approach for the characterization of complex calcium centers in inorganic and bioinorganic chemistry. Herein, Ca K-edge X-ray absorption spectroscopy (XAS) is developed as a means to characterize the local environment of calcium centers. The spectra for six, seven, and eight coordinate inorganic and molecular calcium complexes were analyzed and determined to be primarily influenced by the coordination environment and site symmetry at the calcium center. The experimental results are closely correlated to time-dependent density functional theory (TD-DFT) calculations of the XAS spectra. The applicability of this methodologymore » to complex systems was investigated using structural mimics of the oxygen-evolving complex (OEC) of PSII. It was found that Ca K-edge XAS is a sensitive probe for structural changes occurring in the cubane heterometallic cluster due to Mn oxidation. Future applications to the OEC are discussed.« less

Electrosynthesis of Biomimetic Manganese-Calcium Oxides for Water Oxidation Catalysis--Atomic Structure and Functionality.

PubMed

González-Flores, Diego; Zaharieva, Ivelina; Heidkamp, Jonathan; Chernev, Petko; Martínez-Moreno, Elías; Pasquini, Chiara; Mohammadi, Mohammad Reza; Klingan, Katharina; Gernet, Ulrich; Fischer, Anna; Dau, Holger

2016-02-19

Water-oxidizing calcium-manganese oxides, which mimic the inorganic core of the biological catalyst, were synthesized and structurally characterized by X-ray absorption spectroscopy at the manganese and calcium K edges. The amorphous, birnesite-type oxides are obtained through a simple protocol that involves electrodeposition followed by active-site creation through annealing at moderate temperatures. Calcium ions are inessential, but tune the electrocatalytic properties. For increasing calcium/manganese molar ratios, both Tafel slopes and exchange current densities decrease gradually, resulting in optimal catalytic performance at calcium/manganese molar ratios of close to 10 %. Tracking UV/Vis absorption changes during electrochemical operation suggests that inactive oxides reach their highest, all-Mn(IV) oxidation state at comparably low electrode potentials. The ability to undergo redox transitions and the presence of a minor fraction of Mn(III) ions at catalytic potentials is identified as a prerequisite for catalytic activity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Calcium-sensitive MRI contrast agents based on superparamagnetic iron oxide nanoparticles and calmodulin

PubMed Central

Atanasijevic, Tatjana; Shusteff, Maxim; Fam, Peter; Jasanoff, Alan

2006-01-01

We describe a family of calcium indicators for magnetic resonance imaging (MRI), formed by combining a powerful iron oxide nanoparticle-based contrast mechanism with the versatile calcium-sensing protein calmodulin and its targets. Calcium-dependent protein–protein interactions drive particle clustering and produce up to 5-fold changes in T2 relaxivity, an indication of the sensors' potency. A variant based on conjugates of wild-type calmodulin and the peptide M13 reports concentration changes near 1 μM Ca2+, suitable for detection of elevated intracellular calcium levels. The midpoint and cooperativity of the response can be tuned by mutating the protein domains that actuate the sensor. Robust MRI signal changes are achieved even at nanomolar particle concentrations (<1 μM in calmodulin) that are unlikely to buffer calcium levels. When combined with technologies for cellular delivery of nanoparticulate agents, these sensors and their derivatives may be useful for functional molecular imaging of biological signaling networks in live, opaque specimens. PMID:17003117

Calcium-sensitive MRI contrast agents based on superparamagnetic iron oxide nanoparticles and calmodulin.

PubMed

Atanasijevic, Tatjana; Shusteff, Maxim; Fam, Peter; Jasanoff, Alan

2006-10-03

We describe a family of calcium indicators for magnetic resonance imaging (MRI), formed by combining a powerful iron oxide nanoparticle-based contrast mechanism with the versatile calcium-sensing protein calmodulin and its targets. Calcium-dependent protein-protein interactions drive particle clustering and produce up to 5-fold changes in T2 relaxivity, an indication of the sensors' potency. A variant based on conjugates of wild-type calmodulin and the peptide M13 reports concentration changes near 1 microM Ca(2+), suitable for detection of elevated intracellular calcium levels. The midpoint and cooperativity of the response can be tuned by mutating the protein domains that actuate the sensor. Robust MRI signal changes are achieved even at nanomolar particle concentrations (<1 microM in calmodulin) that are unlikely to buffer calcium levels. When combined with technologies for cellular delivery of nanoparticulate agents, these sensors and their derivatives may be useful for functional molecular imaging of biological signaling networks in live, opaque specimens.

Peripheral Serotonin Regulates Maternal Calcium Trafficking in Mammary Epithelial Cells during Lactation in Mice

PubMed Central

Laporta, Jimena; Keil, Kimberly P.; Vezina, Chad M.; Hernandez, Laura L.

2014-01-01

Lactation is characterized by massive transcellular flux of calcium, from the basolateral side of the mammary alveolar epithelium (blood) into the ductal lumen (milk). Regulation of calcium transport during lactation is critical for maternal and neonatal health. The monoamine serotonin (5-HT) is synthesized by the mammary gland and functions as a homeostatic regulation of lactation. Genetic ablation of tryptophan hydroxylase 1 (Tph1), which encodes the rate-limiting enzyme in non-neuronal serotonin synthesis, causes a deficiency in circulating serotonin. As a consequence maternal calcium concentrations decrease, mammary epithelial cell morphology is altered, and cell proliferation is decreased during lactation. Here we demonstrate that serotonin deficiency decreases the expression and disrupts the normal localization of calcium transporters located in the apical (PMCA2) and basolateral (CaSR, ORAI-1) membranes of the lactating mammary gland. In addition, serotonin deficiency decreases the mRNA expression of calcium transporters located in intracellular compartments (SERCA2, SPCA1 and 2). Mammary expression of serotonin receptor isoform 2b and its downstream pathways (PLCβ3, PKC and MAP-ERK1/2) are also decreased by serotonin deficiency, which might explain the numerous phenotypic alterations described above. In most cases, addition of exogenous 5-hydroxy-L-tryptophan to the Tph1 deficient mice rescued the phenotype. Our data supports the hypothesis that serotonin is necessary for proper mammary gland structure and function, to regulate blood and mammary epithelial cell transport of calcium during lactation. These findings can be applicable to the treatment of lactation-induced hypocalcemia in dairy cows and can have profound implications in humans, given the wide-spread use of selective serotonin reuptake inhibitors as antidepressants during pregnancy and lactation. PMID:25299122

Effect of temperature and pH on the solubility of caseins: environmental influences on the dissociation of α(S)- and β-casein.

PubMed

Post, A E; Arnold, B; Weiss, J; Hinrichs, J

2012-04-01

Selective precipitation is a common method for the isolation of β-casein, using the different calcium sensitivities of the individual caseins and the selective solubility of β-casein at a low temperature. In previous studies, it has been indicated that the β-casein yield depends on the physicochemical characteristics of the casein raw material used for fractionation. The objective of this study was to evaluate and compare the solubility of α(S)- and β-casein in solutions of micellar casein, sodium caseinate, and calcium caseinate as a function of pH and temperature. Additionally, the solubility of isolated α(S)- and β-casein fractions in demineralized water, ultrafiltration permeate, and a calcium-depleted milk salt solution was investigated depending on the pH and temperature. Furthermore, micellar casein, sodium caseinate, and calcium caseinate were subjected to a calcium chloride-precipitation process to determine the solubility of α(S)- and β-casein in calcium chloride precipitate, which is produced during selective precipitation, as a function of temperature and pH. Generally, the temperature had only a marginal influence on the α(S)-casein solubility compared with the β-casein solubility, whereas the solubility was shown to be strongly influenced by the pH. Our results suggest that the yield of β-casein obtained during isolation by means of selective precipitation may be a result of the solubility characteristics of α(S)- and β-casein in calcium chloride precipitate. Manufacturers may consider a simple solubility experiment before the β-casein isolation process by means of selective precipitation to predict β-casein yield. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The effects of vasoactive peptide urocortin 2 on hemodynamics in spontaneous hypertensive rat and the role of L-type calcium channel and CRFR2.

PubMed

Liu, Chunna; Liu, Xinyu; Yang, Jing; Duan, Yan; Yao, Hongyue; Li, Fenghua; Zhang, Xia

2015-04-01

Urocortin (UCN) is a newly identified vascular-active peptide that has been shown to reverse cardiovascular remodeling and improve left ventricular (LV) function. The effects and mechanism of urocortin 2 (UCN2) in vivo on the electrical remodeling of left ventricle and the hemodynamics of hypertensive objectives have not been investigated. UCN2 (1 μg/kg/d, 3.5 μg/kg/d or 7 μg/kg/d) was intravenously injected for 2 weeks and its effects on hemodynamics in spontaneously hypertensive rats (SHRs) observed. The whole-cell patch clamp technique was used to explore the effects of UCN2 on the electrical remodeling of left ventricular cardiomyocytes. The flow cytometry method was used to determine the content of fluorescence calcium in myocardium. UCN2 improved the systolic and diastolic function of SHRs as demonstrated by decreased left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), increased +dp/dtmax and -dp/dtmax and decreased cAMP level. UCN2 inhibited the opening of L-type calcium channel and decreased the calcium channel current of cardiomyocytes. In addition, UCN2 also decreased the contents of fluorescence calcium in SHR myocardium. However, astressin2-B (AST-2B), the antagonist of corticotropin-releasing factor receptor 2 (CRFR2), could reverse the inhibitory effects of UCN2 on calcium channel. UCN2 can modulate electrical remodeling of the myocardium and hemodynamics in an experimental model of SHR via inhibition of L-type calcium channel and CRFR2 in cardiomyocytes. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

LcrV Mutants That Abolish Yersinia Type III Injectisome Function

PubMed Central

Ligtenberg, Katherine Given; Miller, Nathan C.; Mitchell, Anthony; Plano, Gregory V.

2013-01-01

LcrV, the type III needle cap protein of pathogenic Yersinia, has been proposed to function as a tether between YscF, the needle protein, and YopB-YopD to constitute the injectisome, a conduit for the translocation of effector proteins into host cells. Further, insertion of LcrV-capped needles from a calcium-rich environment into host cells may trigger the low-calcium signal for effector translocation. Here, we used a genetic approach to test the hypothesis that the needle cap responds to the low-calcium signal by promoting injectisome assembly. Growth restriction of Yersinia pestis in the absence of calcium (low-calcium response [LCR+] phenotype) was exploited to isolate dominant negative lcrV alleles with missense mutations in its amber stop codon (lcrV*327). The addition of at least four amino acids or the eight-residue Strep tag to the C terminus was sufficient to generate an LCR− phenotype, with variant LcrV capping type III needles that cannot assemble the YopD injectisome component. The C-terminal Strep tag appears buried within the cap structure, blocking effector transport even in Y. pestis yscF variants that are otherwise calcium blind, a constitutive type III secretion phenotype. Thus, LcrV*327 mutants arrest the needle cap in a state in which it cannot respond to the low-calcium signal with either injectisome assembly or the activation of type III secretion. Insertion of the Strep tag at other positions of LcrV produced variants with wild-type LCR+, LCR−, or dominant negative LCR− phenotypes, thereby allowing us to identify discrete sites within LcrV as essential for its attributes as a secretion substrate, needle cap, and injectisome assembly factor. PMID:23222719

NADPH Oxidase 5 Is a Pro-Contractile Nox Isoform and a Point of Cross-Talk for Calcium and Redox Signaling-Implications in Vascular Function.

PubMed

Montezano, Augusto C; De Lucca Camargo, Livia; Persson, Patrik; Rios, Francisco J; Harvey, Adam P; Anagnostopoulou, Aikaterini; Palacios, Roberto; Gandara, Ana Caroline P; Alves-Lopes, Rheure; Neves, Karla B; Dulak-Lis, Maria; Holterman, Chet E; de Oliveira, Pedro Lagerblad; Graham, Delyth; Kennedy, Christopher; Touyz, Rhian M

2018-06-15

NADPH Oxidase 5 (Nox5) is a calcium-sensitive superoxide-generating Nox. It is present in lower forms and higher mammals, but not in rodents. Nox5 is expressed in vascular cells, but the functional significance remains elusive. Given that contraction is controlled by calcium and reactive oxygen species, both associated with Nox5, we questioned the role of Nox5 in pro-contractile signaling and vascular function. Transgenic mice expressing human Nox5 in a vascular smooth muscle cell-specific manner (Nox5 mice) and Rhodnius prolixus , an arthropod model that expresses Nox5 endogenoulsy, were studied. Reactive oxygen species generation was increased systemically and in the vasculature and heart in Nox5 mice. In Nox5-expressing mice, agonist-induced vasoconstriction was exaggerated and endothelium-dependent vasorelaxation was impaired. Vascular structural and mechanical properties were not influenced by Nox5. Vascular contractile responses in Nox5 mice were normalized by N -acetylcysteine and inhibitors of calcium channels, calmodulin, and endoplasmic reticulum ryanodine receptors, but not by GKT137831 (Nox1/4 inhibitor). At the cellular level, vascular changes in Nox5 mice were associated with increased vascular smooth muscle cell [Ca 2+ ] i , increased reactive oxygen species and nitrotyrosine levels, and hyperphosphorylation of pro-contractile signaling molecules MLC20 (myosin light chain 20) and MYPT1 (myosin phosphatase target subunit 1). Blood pressure was similar in wild-type and Nox5 mice. Nox5 did not amplify angiotensin II effects. In R. prolixus , gastrointestinal smooth muscle contraction was blunted by Nox5 silencing, but not by VAS2870 (Nox1/2/4 inhibitor). Nox5 is a pro-contractile Nox isoform important in redox-sensitive contraction. This involves calcium-calmodulin and endoplasmic reticulum-regulated mechanisms. Our findings define a novel function for vascular Nox5, linking calcium and reactive oxygen species to the pro-contractile molecular machinery in vascular smooth muscle cells. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

All‐optical functional synaptic connectivity mapping in acute brain slices using the calcium integrator CaMPARI

PubMed Central

Sha, Fern; Johenning, Friedrich W.; Schreiter, Eric R.; Looger, Loren L.; Larkum, Matthew E.

2016-01-01

Key points The genetically encoded fluorescent calcium integrator calcium‐modulated photoactivatable ratiobetric integrator (CaMPARI) reports calcium influx induced by synaptic and neural activity. Its fluorescence is converted from green to red in the presence of violet light and calcium.The rate of conversion – the sensitivity to activity – is tunable and depends on the intensity of violet light.Synaptic activity and action potentials can independently initiate significant CaMPARI conversion.The level of conversion by subthreshold synaptic inputs is correlated to the strength of input, enabling optical readout of relative synaptic strength.When combined with optogenetic activation of defined presynaptic neurons, CaMPARI provides an all‐optical method to map synaptic connectivity. Abstract The calcium‐modulated photoactivatable ratiometric integrator (CaMPARI) is a genetically encoded calcium integrator that facilitates the study of neural circuits by permanently marking cells active during user‐specified temporal windows. Permanent marking enables measurement of signals from large swathes of tissue and easy correlation of activity with other structural or functional labels. One potential application of CaMPARI is labelling neurons postsynaptic to specific populations targeted for optogenetic stimulation, giving rise to all‐optical functional connectivity mapping. Here, we characterized the response of CaMPARI to several common types of neuronal calcium signals in mouse acute cortical brain slices. Our experiments show that CaMPARI is effectively converted by both action potentials and subthreshold synaptic inputs, and that conversion level is correlated to synaptic strength. Importantly, we found that conversion rate can be tuned: it is linearly related to light intensity. At low photoconversion light levels CaMPARI offers a wide dynamic range due to slower conversion rate; at high light levels conversion is more rapid and more sensitive to activity. Finally, we employed CaMPARI and optogenetics for functional circuit mapping in ex vivo acute brain slices, which preserve in vivo‐like connectivity of axon terminals. With a single light source, we stimulated channelrhodopsin‐2‐expressing long‐range posteromedial (POm) thalamic axon terminals in cortex and induced CaMPARI conversion in recipient cortical neurons. We found that POm stimulation triggers robust photoconversion of layer 5 cortical neurons and weaker conversion of layer 2/3 neurons. Thus, CaMPARI enables network‐wide, tunable, all‐optical functional circuit mapping that captures supra‐ and subthreshold depolarization. PMID:27861906

PTK2b function during fertilization of the mouse oocyte

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Jinping; McGinnis, Lynda K.; Carlton, Carol

Highlights: • PTK2b is expressed in oocytes and is activated following fertilization. • PTK2b suppression in oocytes prevents fertilization, but not parthenogenetic activation. • PTK2b suppression prevents the oocyte from fusing with or incorporating bound sperm. • PTK2b suppressed oocytes that fail to fertilize do not exhibit calcium oscillations. - Abstract: Fertilization triggers rapid changes in intracellular free calcium that serve to activate multiple signaling events critical to the initiation of successful development. Among the pathways downstream of the fertilization-induced calcium transient is the calcium-calmodulin dependent protein tyrosine kinase PTK2b or PYK2 kinase. PTK2b plays an important role in fertilizationmore » of the zebrafish oocyte and the objective of the present study was to establish whether PTK2b also functions in mammalian fertilization. PTK2b was activated during the first few hours after fertilization of the mouse oocyte during the period when anaphase resumption was underway and prior to the pronuclear stage. Suppression of PTK2b kinase activity in oocytes blocked sperm incorporation and egg activation although sperm-oocyte binding was not affected. Oocytes that failed to incorporate sperm after inhibitor treatment showed no evidence of a calcium transient and no evidence of anaphase resumption suggesting that egg activation did not occur. The results indicate that PTK2b functions during the sperm-egg fusion process or during the physical incorporation of sperm into the egg cytoplasm and is therefore critical for successful development.« less

LRP1 influences trafficking of N-type calcium channels via interaction with the auxiliary α2δ-1 subunit

PubMed Central

Kadurin, Ivan; Rothwell, Simon W.; Lana, Beatrice; Nieto-Rostro, Manuela; Dolphin, Annette C.

2017-01-01

Voltage-gated Ca2+ (CaV) channels consist of a pore-forming α1 subunit, which determines the main functional and pharmacological attributes of the channel. The CaV1 and CaV2 channels are associated with auxiliary β- and α2δ-subunits. The molecular mechanisms involved in α2δ subunit trafficking, and the effect of α2δ subunits on trafficking calcium channel complexes remain poorly understood. Here we show that α2δ-1 is a ligand for the Low Density Lipoprotein (LDL) Receptor-related Protein-1 (LRP1), a multifunctional receptor which mediates trafficking of cargoes. This interaction with LRP1 is direct, and is modulated by the LRP chaperone, Receptor-Associated Protein (RAP). LRP1 regulates α2δ binding to gabapentin, and influences calcium channel trafficking and function. Whereas LRP1 alone reduces α2δ-1 trafficking to the cell-surface, the LRP1/RAP combination enhances mature glycosylation, proteolytic processing and cell-surface expression of α2δ-1, and also increase plasma-membrane expression and function of CaV2.2 when co-expressed with α2δ-1. Furthermore RAP alone produced a small increase in cell-surface expression of CaV2.2, α2δ-1 and the associated calcium currents. It is likely to be interacting with an endogenous member of the LDL receptor family to have these effects. Our findings now provide a key insight and new tools to investigate the trafficking of calcium channel α2δ subunits. PMID:28256585

Intervention and follow-up on human esophageal precancerous lesions in Henan, northern China, a high-incidence area for esophageal cancer.

PubMed

Wang, Li Dong; Zhou, Qi; Feng, Chang Wei; Liu, Bin; Qi, Yi Jun; Zhang, Yan Run; Gao, Shan Shan; Fan, Zong Min; Zhou, Yun; Yang, Chang S; Wei, Jun Ping; Zheng, Shu

2002-02-01

Esophageal cancer (EC) remains a leading cause of cancer-related deaths in Linzhou (formerly Linxian) and Huixian of Henan province, northern China, which has been well recognized as the highest incidence area for EC. The lack of useful chemoprevention agents and early detection methods is the key factors for stable EC incidence in these areas. Human esophageal carcinogensis has been considered as a multistep progressive process. The natural history for EC, however is not very clear. Follow-up studies with linear repeated biopsies and histopathological examination were performed on 778 subjects from Linzhou and Huixian. Of these subjects, 578 subjects were followed for 11 years (1989-2000), 400 subjects with different severity of esophageal precancerous lesions were randomly divided into 2 groups for intervention studies with calcium and decaffeinated green tea (DGT). Each group included 200 subjects (100 subjects for treatment, and 100 subjects for placebo). In calcium group, each subject received an oral supplementation of 1,200 mg of calcium daily for 11 months. In DGT group, each subject received 5 mg of DGT daily for 12 months. In placebo group, each subject received placebo pill for 11 months (calcium group) and 12 month (DGT group). At the entry and the end of the trial, esophageal biopsy specimens were taken at the middle and the lower thirds of the esophagus and from macroscopic lesions, if only, of each subject. DGT trail did not show apparent difference between the treatment and placebo group in alleviating the esophageal precancerous lesions and abnormal cell proliferation. For the calcium intervention study, after 11 years' follow-up, 10 subjects had developed into cancers in the calcium group (10%, 8 EC and 2 GCA), and 8 subjects developed into EC in the placebo group (8%). All these patients were diagnosed at very early stage of cancer (symptom-free). Of the 578 subjects, 25 (18 males and 7 females) had developed into EC (n = 23, 4.3%) and gastric cardia cancer (GCA, n = 2, 0.3%), during the 11 years' follow-up. The mean time of cancer development (from entry of the follow-up study to the cancer detection) was 5.0 +/- 2.9 years (males) and 4.7 +/- 3.2 years (females). Of the 25 patients with EC and GCA, 11 were from the 387 followed subjects with "normal" histomorphology of biopsy at the entry of the follow-up study (3%, 11/387), 2 were from the subjects with basal cell hyperplasia, grade I (BCH I, 2%, 2/94), 7 from the subjects with BCH grade II (BCH II, 10%, 7/72), and 5 from BCH III and dysplasia (20%, 5/25). DGT trail was not shown to have beneficial effects in alleviating esophageal precancerous lesions and abnormal cell proliferation patterns. Calcium supplementation did not produce apparent long-term effects on EC. BCH II could be considered as precancerous lesions of EC. The quantitative histopathological analysis in terms of number of proliferating basal cell layers is of importance in determining the high-risk subjects for EC and evaluating the intervention results. Follow-up studies with repeated endoscopic biopsies are the powerful strategy for early detection and mortality control of EC and GAC in the high incidence area.

Development of bioactive porous α-TCP/HAp beads for bone tissue engineering.

PubMed

Asaoka, Teruo; Ohtake, Shoji; Furukawa, Katsuko S; Tamura, Akito; Ushida, Takashi

2013-11-01

Porous beads of bioactive ceramics such as hydroxyapatite (HAp) and tribasic calcium phosphate (TCP) are considered a promising scaffold for cultivating bone cells. To realize this, α-TCP/HAp functionally graded porous beads are fabricated with two main purposes: to maintain the function of the scaffold with sufficient strength up to the growth of new bone, and is absorbed completely after the growth. HAp is a bioactive material that has both high strength and strong tissue-adhesive properties, but is not readily absorbed by the human body. On the contrary, α-TCP is highly bioabsorbable, resulting in a scaffold that is absorbed before it is completely replaced by bone. In this study, we produced porous, bead-shaped carriers as scaffolds for osteoblast culture. To control the solubility in vivo, the fabricated beads contained α-TCP at the center and HAp at the surface. Cell adaptability of these beads for bone tissue engineering was confirmed in vitro. It was found that α-TCP/HAp bead carriers exhibit low toxicity in the initial stages of cell seeding and cell adhesion. The presence of HAp in the composite bead form effectively increased ALP activity. In conclusion, it is suggested that these newly developed α-TCP/HAp beads are a promising tool for bone tissue engineering. Copyright © 2013 Wiley Periodicals, Inc.

Fast activation of dihydropyridine-sensitive calcium channels of skeletal muscle. Multiple pathways of channel gating

PubMed Central

1996-01-01

Dihydropyridine (DHP) receptors of the transverse tubule membrane play two roles in excitation-contraction coupling in skeletal muscle: (a) they function as the voltage sensor which undergoes fast transition to control release of calcium from sarcoplasmic reticulum, and (b) they provide the conducting unit of a slowly activating L-type calcium channel. To understand this dual function of the DHP receptor, we studied the effect of depolarizing conditioning pulse on the activation kinetics of the skeletal muscle DHP-sensitive calcium channels reconstituted into lipid bilayer membranes. Activation of the incorporated calcium channel was imposed by depolarizing test pulses from a holding potential of -80 mV. The gating kinetics of the channel was studied with ensemble averages of repeated episodes. Based on a first latency analysis, two distinct classes of channel openings occurred after depolarization: most had delayed latencies, distributed with a mode of 70 ms (slow gating); a small number of openings had short first latencies, < 12 ms (fast gating). A depolarizing conditioning pulse to +20 mV placed 200 ms before the test pulse (-10 mV), led to a significant increase in the activation rate of the ensemble averaged-current; the time constant of activation went from tau m = 110 ms (reference) to tau m = 45 ms after conditioning. This enhanced activation by the conditioning pulse was due to the increase in frequency of fast open events, which was a steep function of the intermediate voltage and the interval between the conditioning pulse and the test pulse. Additional analysis demonstrated that fast gating is the property of the same individual channels that normally gate slowly and that the channels adopt this property after a sojourn in the open state. The rapid secondary activation seen after depolarizing prepulses is not compatible with a linear activation model for the calcium channel, but is highly consistent with a cyclical model. A six- state cyclical model is proposed for the DHP-sensitive Ca channel, which pictures the normal pathway of activation of the calcium channel as two voltage-dependent steps in sequence, plus a voltage-independent step which is rate limiting. The model reproduced well the fast and slow gating models of the calcium channel, and the effects of conditioning pulses. It is possible that the voltage-sensitive gating transitions of the DHP receptor, which occur early in the calcium channel activation sequence, could underlie the role of the voltage sensor and yield the rapid excitation-contraction coupling in skeletal muscle, through either electrostatic or allosteric linkage to the ryanodine receptors/calcium release channels. PMID:8882865

Thyroid C-Cell Biology and Oncogenic Transformation

PubMed Central

Cote, Gilbert J.; Grubbs, Elizabeth G.; Hofmann, Marie-Claude

2017-01-01

The thyroid parafollicular cell, or commonly named “C-cell,” functions in serum calcium homeostasis. Elevations in serum calcium trigger release of calcitonin from the C-cell, which in turn functions to inhibit absorption of calcium by the intestine, resorption of bone by the osteoclast, and reabsorption of calcium by renal tubular cells. Oncogenic transformation of the thyroid C-cell is thought to progress through a hyperplastic process prior to malignancy with increasing levels of serum calcitonin serving as a biomarker for tumor burden. The discovery that Multiple Endocrine Neoplasia, type 2 is caused by activating mutations of the RET gene serves to highlight the RET-RAS-MAPK signaling pathway in both initiation and progression of medullary thyroid carcinoma. Thyroid C-cells are known to express RET at high levels relative to most cell types, therefore aberrant activation of this receptor is targeted primarily to the C-cell, providing one possible cause of tissue-specific oncogenesis. The role of RET signaling in normal C-cell function is unknown though calcitonin gene transcription appears to be sensitive to RET activation. Beyond RET the modeling of oncogenesis in animals and screening of human tumors for candidate gene mutations has uncovered mutation of RAS family members and inactivation of Rb1 regulatory pathway as potential mediators of C-cell transformation. A growing understanding of how RET interacts with these pathways, both in normal C-cell function and during oncogenic transformation will help in the development of novel molecular targeted therapies. PMID:26494382

TRIENNIAL LACTATION SYMPOSIUM/BOLFA: Serotonin and the regulation of calcium transport in dairy cows.

PubMed

Hernandez, L L

2017-12-01

The mammary gland regulates maternal metabolism during lactation. Numerous factors within the tissue send signals to shift nutrients to the mammary gland for milk synthesis. Serotonin is a monoamine that has been well documented to regulate several aspects of lactation among species. Maintenance of maternal calcium homeostasis during lactation is a highly evolved process that is elegantly regulated by the interaction of the mammary gland with the bone, gut, and kidney tissues. It is well documented that dietary calcium is insufficient to maintain maternal calcium concentrations during lactation, and mammals must rely on bone resorption to maintain normocalcemia. Our recent work focused on the ability of the mammary gland to function as an accessory parathyroid gland during lactation. It was demonstrated that serotonin acts to stimulate parathyroid hormone-related protein (PTHrP) in the mammary gland during lactation. The main role of mammary-derived PTHrP during mammalian lactation is to stimulate bone resorption to maintain maternal calcium homeostasis during lactation. In addition to regulating PTHrP, it was shown that serotonin appears to directly affect calcium transporters and pumps in the mammary gland. Our current working hypothesis regarding the control of calcium during lactation is as follows: serotonin directly stimulates PTHrP production in the mammary gland through interaction with the sonic hedgehog signaling pathway. Simultaneously, serotonin directly increases calcium movement into the mammary gland and, subsequently, milk. These 2 direct actions of serotonin combine to induce a transient maternal hypocalcemia required to further stimulate PTHrP production and calcium mobilization from bone. Through these 2 routes, serotonin is able to improve maternal calcium concentrations. Furthermore, we have shown that Holstein and Jersey cows appear to regulate calcium in different manners and also respond differently to serotonergic stimulation of the calcium pathway. Our data in rodents and cows indicate that serotonin and calcium are working through a unique feedback loop with PTHrP during lactation to regulate milk calcium and maternal calcium homeostasis.

Fruit Calcium: Transport and Physiology

PubMed Central

Hocking, Bradleigh; Tyerman, Stephen D.; Burton, Rachel A.; Gilliham, Matthew

2016-01-01

Calcium has well-documented roles in plant signaling, water relations and cell wall interactions. Significant research into how calcium impacts these individual processes in various tissues has been carried out; however, the influence of calcium on fruit ripening has not been thoroughly explored. Here, we review the current state of knowledge on how calcium may impact the development, physical traits and disease susceptibility of fruit through facilitating developmental and stress response signaling, stabilizing membranes, influencing water relations and modifying cell wall properties through cross-linking of de-esterified pectins. We explore the involvement of calcium in hormone signaling integral to the physiological mechanisms behind common disorders that have been associated with fruit calcium deficiency (e.g., blossom end rot in tomatoes or bitter pit in apples). This review works toward an improved understanding of how the many roles of calcium interact to influence fruit ripening, and proposes future research directions to fill knowledge gaps. Specifically, we focus mostly on grapes and present a model that integrates existing knowledge around these various functions of calcium in fruit, which provides a basis for understanding the physiological impacts of sub-optimal calcium nutrition in grapes. Calcium accumulation and distribution in fruit is shown to be highly dependent on water delivery and cell wall interactions in the apoplasm. Localized calcium deficiencies observed in particular species or varieties can result from differences in xylem morphology, fruit water relations and pectin composition, and can cause leaky membranes, irregular cell wall softening, impaired hormonal signaling and aberrant fruit development. We propose that the role of apoplasmic calcium-pectin crosslinking, particularly in the xylem, is an understudied area that may have a key influence on fruit water relations. Furthermore, we believe that improved knowledge of the calcium-regulated signaling pathways that control ripening would assist in addressing calcium deficiency disorders and improving fruit pathogen resistance. PMID:27200042

Transcriptome Wide Identification and Validation of Calcium Sensor Gene Family in the Developing Spikes of Finger Millet Genotypes for Elucidating Its Role in Grain Calcium Accumulation

PubMed Central

Singh, Uma M.; Chandra, Muktesh; Shankhdhar, Shailesh C.; Kumar, Anil

2014-01-01

Background In finger millet, calcium is one of the important and abundant mineral elements. The molecular mechanisms involved in calcium accumulation in plants remains poorly understood. Transcriptome sequencing of genetically diverse genotypes of finger millet differing in grain calcium content will help in understanding the trait. Principal Finding In this study, the transcriptome sequencing of spike tissues of two genotypes of finger millet differing in their grain calcium content, were performed for the first time. Out of 109,218 contigs, 78 contigs in case of GP-1 (Low Ca genotype) and out of 120,130 contigs 76 contigs in case of GP-45 (High Ca genotype), were identified as calcium sensor genes. Through in silico analysis all 82 unique calcium sensor genes were classified into eight calcium sensor gene family viz., CaM & CaMLs, CBLs, CIPKs, CRKs, PEPRKs, CDPKs, CaMKs and CCaMK. Out of 82 genes, 12 were found diverse from the rice orthologs. The differential expression analysis on the basis of FPKM value resulted in 24 genes highly expressed in GP-45 and 11 genes highly expressed in GP-1. Ten of the 35 differentially expressed genes could be assigned to three documented pathways involved mainly in stress responses. Furthermore, validation of selected calcium sensor responder genes was also performed by qPCR, in developing spikes of both genotypes grown on different concentration of exogenous calcium. Conclusion Through de novo transcriptome data assembly and analysis, we reported the comprehensive identification and functional characterization of calcium sensor gene family. The calcium sensor gene family identified and characterized in this study will facilitate in understanding the molecular basis of calcium accumulation and development of calcium biofortified crops. Moreover, this study also supported that identification and characterization of gene family through Illumina paired-end sequencing is a potential tool for generating the genomic information of gene family in non-model species. PMID:25157851

Transcriptome wide identification and validation of calcium sensor gene family in the developing spikes of finger millet genotypes for elucidating its role in grain calcium accumulation.

PubMed

Singh, Uma M; Chandra, Muktesh; Shankhdhar, Shailesh C; Kumar, Anil

2014-01-01

In finger millet, calcium is one of the important and abundant mineral elements. The molecular mechanisms involved in calcium accumulation in plants remains poorly understood. Transcriptome sequencing of genetically diverse genotypes of finger millet differing in grain calcium content will help in understanding the trait. In this study, the transcriptome sequencing of spike tissues of two genotypes of finger millet differing in their grain calcium content, were performed for the first time. Out of 109,218 contigs, 78 contigs in case of GP-1 (Low Ca genotype) and out of 120,130 contigs 76 contigs in case of GP-45 (High Ca genotype), were identified as calcium sensor genes. Through in silico analysis all 82 unique calcium sensor genes were classified into eight calcium sensor gene family viz., CaM & CaMLs, CBLs, CIPKs, CRKs, PEPRKs, CDPKs, CaMKs and CCaMK. Out of 82 genes, 12 were found diverse from the rice orthologs. The differential expression analysis on the basis of FPKM value resulted in 24 genes highly expressed in GP-45 and 11 genes highly expressed in GP-1. Ten of the 35 differentially expressed genes could be assigned to three documented pathways involved mainly in stress responses. Furthermore, validation of selected calcium sensor responder genes was also performed by qPCR, in developing spikes of both genotypes grown on different concentration of exogenous calcium. Through de novo transcriptome data assembly and analysis, we reported the comprehensive identification and functional characterization of calcium sensor gene family. The calcium sensor gene family identified and characterized in this study will facilitate in understanding the molecular basis of calcium accumulation and development of calcium biofortified crops. Moreover, this study also supported that identification and characterization of gene family through Illumina paired-end sequencing is a potential tool for generating the genomic information of gene family in non-model species.

Global Consensus Recommendations on Prevention and Management of Nutritional Rickets.

PubMed

Munns, Craig F; Shaw, Nick; Kiely, Mairead; Specker, Bonny L; Thacher, Tom D; Ozono, Keiichi; Michigami, Toshimi; Tiosano, Dov; Mughal, M Zulf; Mäkitie, Outi; Ramos-Abad, Lorna; Ward, Leanne; DiMeglio, Linda A; Atapattu, Navoda; Cassinelli, Hamilton; Braegger, Christian; Pettifor, John M; Seth, Anju; Idris, Hafsatu Wasagu; Bhatia, Vijayalakshmi; Fu, Junfen; Goldberg, Gail; Sävendahl, Lars; Khadgawat, Rajesh; Pludowski, Pawel; Maddock, Jane; Hyppönen, Elina; Oduwole, Abiola; Frew, Emma; Aguiar, Magda; Tulchinsky, Ted; Butler, Gary; Högler, Wolfgang

2016-02-01

Vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a major impact on health, growth, and development of infants, children, and adolescents; the consequences can be lethal or can last into adulthood. The goals of this evidence-based consensus document are to provide health care professionals with guidance for prevention, diagnosis, and management of nutritional rickets and to provide policy makers with a framework to work toward its eradication. A systematic literature search examining the definition, diagnosis, treatment, and prevention of nutritional rickets in children was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system that describe the strength of the recommendation and the quality of supporting evidence. Thirty-three nominated experts in pediatric endocrinology, pediatrics, nutrition, epidemiology, public health, and health economics evaluated the evidence on specific questions within five working groups. The consensus group, representing 11 international scientific organizations, participated in a multiday conference in May 2014 to reach a global evidence-based consensus. This consensus document defines nutritional rickets and its diagnostic criteria and describes the clinical management of rickets and osteomalacia. Risk factors, particularly in mothers and infants, are ranked, and specific prevention recommendations including food fortification and supplementation are offered for both the clinical and public health contexts. Rickets, osteomalacia, and vitamin D and calcium deficiencies are preventable global public health problems in infants, children, and adolescents. Implementation of international rickets prevention programs, including supplementation and food fortification, is urgently required.

Physical characteristics of calcium oxalate crystals as determinants in structural defense against chewing insects in Medicago truncatula

USDA-ARS?s Scientific Manuscript database

In addition to the numerous chemical defenses that plants employ to fend off insect herbivores, simple structural components can also play important roles in effective protection. Our investigations have shown that plant crystals of calcium oxalate can function in insect defense. The isolation of ca...

Investigating structure-property relationships of biomineralized calcium phosphate compounds as fluorescent quenching-recovery platform

NASA Astrophysics Data System (ADS)

Wang, Liuzheng; He, Xiang; Zhang, Wei; Liu, Yong; Banks, Craig E.; Zhang, Ying

2018-02-01

The structure-property relationship between biomineralized calcium phosphate compounds upon a fluorescent quenching-recovery platform and their distinct crystalline structure and surficial functional groups are investigated. A fluorescence-based sensing platform is shown to be viable for the sensing of 8-hydroxy-2-deoxy-guanosine in simulated systems.

Preoperative normal level of parathyroid hormone signifies an early and mild form of primary hyperparathyroidism.

PubMed

Bergenfelz, Anders; Lindblom, Pia; Lindergård, Birger; Valdemarsson, Stig; Westerdahl, Johan

2003-04-01

Contemporary patients are often diagnosed with mild or intermittent hypercalcemia. In addition, most studies demonstrate patients with parathyroid (PTH) levels in the upper normal range. The aim of the present investigation was to define subgroups of patients with mild primary hyperparathyroidism (pHPT), which could be of importance in the decision for or against surgical treatment. Two-hundred and eleven patients, operated for pHPT were investigated with biochemical variables known to reflect PTH activity, renal function, and bone mineral content. The preoperative diagnosis of pHPT was based on the presence of hypercalcemia combined with an inappropriate serum concentration of PTH. The mean age of the patients was 64 +/- 14 years and the mean serum level of calcium was 2.78 +/- 0.19 mmol/L. One hundred and sixty-two patients (77%) had raised levels of calcium and PTH the day before surgery (overt pHPT), 25 patients (12%) had a normal level of calcium and a raised PTH level (normal calcium group), and 20 patients (9%) had a raised level of calcium and a normal level of PTH (normal PTH group). In four patients the level of calcium and PTH was normal. Between-group analysis demonstrated no major difference in symptom and signs of pHPT. Except for lower adenoma weight, patients in the normal calcium group did not essentially differ from the patients in the overt pHPT group. However, patients in the normal PTH group were a decade younger, and had better renal function, lower bone turnover, and a preserved bone density compared with patients in the overt pHPT group. In conclusion, the data from the present investigation show that pHPT patients with a preoperative normal PTH level have an early and mild form of the disease. Furthermore, the serum calcium concentration does not reflect disease severity in pHPT.

Membrane properties involved in calcium-stimulated microparticle release from the plasma membranes of S49 lymphoma cells.

PubMed

Campbell, Lauryl E; Nelson, Jennifer; Gibbons, Elizabeth; Judd, Allan M; Bell, John D

2014-01-01

This study answered the question of whether biophysical mechanisms for microparticle shedding discovered in platelets and erythrocytes also apply to nucleated cells: cytoskeletal disruption, potassium efflux, transbilayer phospholipid migration, and membrane disordering. The calcium ionophore, ionomycin, disrupted the actin cytoskeleton of S49 lymphoma cells and produced rapid release of microparticles. This release was significantly inhibited by interventions that impaired calcium-activated potassium current. Microparticle release was also greatly reduced in a lymphocyte cell line deficient in the expression of scramblase, the enzyme responsible for calcium-stimulated dismantling of the normal phospholipid transbilayer asymmetry. Rescue of the scrambling function at high ionophore concentration also resulted in enhanced particle shedding. The effect of membrane physical properties was addressed by varying the experimental temperature (32-42°C). A significant positive trend in the rate of microparticle release as a function of temperature was observed. Fluorescence experiments with trimethylammonium diphenylhexatriene and Patman revealed significant decrease in the level of apparent membrane order along that temperature range. These results demonstrated that biophysical mechanisms involved in microparticle release from platelets and erythrocytes apply also to lymphocytes.

Activity-induced Ca2+ signaling in perisynaptic Schwann cells of the early postnatal mouse is mediated by P2Y1 receptors and regulates muscle fatigue

PubMed Central

Heredia, Dante J; Feng, Cheng-Yuan; Hennig, Grant W; Renden, Robert B

2018-01-01

Perisynaptic glial cells respond to neural activity by increasing cytosolic calcium, but the significance of this pathway is unclear. Terminal/perisynaptic Schwann cells (TPSCs) are a perisynaptic glial cell at the neuromuscular junction that respond to nerve-derived substances such as acetylcholine and purines. Here, we provide genetic evidence that activity-induced calcium accumulation in neonatal TPSCs is mediated exclusively by one subtype of metabotropic purinergic receptor. In P2ry1 mutant mice lacking these responses, postsynaptic, rather than presynaptic, function was altered in response to nerve stimulation. This impairment was correlated with a greater susceptibility to activity-induced muscle fatigue. Interestingly, fatigue in P2ry1 mutants was more greatly exacerbated by exposure to high potassium than in control mice. High potassium itself increased cytosolic levels of calcium in TPSCs, a response which was also reduced P2ry1 mutants. These results suggest that activity-induced calcium responses in TPSCs regulate postsynaptic function and muscle fatigue by regulating perisynaptic potassium. PMID:29384476

Regulation of AQP0 water permeability is enhanced by cooperativity

PubMed Central

Németh-Cahalan, Karin L.; Clemens, Daniel M.

2013-01-01

Aquaporin 0 (AQP0), essential for lens clarity, is a tetrameric protein composed of four identical monomers, each of which has its own water pore. The water permeability of AQP0 expressed in Xenopus laevis oocytes can be approximately doubled by changes in calcium concentration or pH. Although each monomer pore functions as a water channel, under certain conditions the pores act cooperatively. In other words, the tetramer is the functional unit. In this paper, we show that changes in external pH and calcium can induce an increase in water permeability that exhibits either a positive cooperativity switch-like increase in water permeability or an increase in water permeability in which each monomer acts independently and additively. Because the concentrations of calcium and hydrogen ions increase toward the center of the lens, a concentration signal could trigger a regulatory change in AQP0 water permeability. It thus seems plausible that the cooperative modes of water permeability regulation by AQP0 tetramers mediated by decreased pH and elevated calcium are the physiologically important ones in the living lens. PMID:23440275

Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kosmidis, Georgios; Bellin, Milena; Ribeiro, Marcelo C.

One limitation in using human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) for disease modeling and cardiac safety pharmacology is their immature functional phenotype compared with adult cardiomyocytes. Here, we report that treatment of human embryonic stem cell derived cardiomyocytes (hESC-CMs) with dexamethasone, a synthetic glucocorticoid, activated glucocorticoid signaling which in turn improved their calcium handling properties and contractility. L-type calcium current and action potential properties were not affected by dexamethasone but significantly faster calcium decay, increased forces of contraction and sarcomeric lengths, were observed in hESC-CMs after dexamethasone exposure. Activating the glucocorticoid pathway can thus contribute to mediating hPSC-CMs maturation.more » - Highlights: • Dexamethasone accelerates Ca{sup 2+} transient decay in hESC-CMs. • Dexamethasone enhances SERCA and NCX function in hESC-CMs. • Dexamethasone increases force of contraction and sarcomere length in hESC-CMs. • Dexamethasone does not alter I{sub Ca,L} and action potential characteristics in hESC-CMs.« less

Calcium-manganese oxides as structural and functional models for active site in oxygen evolving complex in photosystem II: lessons from simple models.

PubMed

Najafpour, Mohammad Mahdi

2011-01-01

The oxygen evolving complex in photosystem II which induces the oxidation of water to dioxygen in plants, algae and certain bacteria contains a cluster of one calcium and four manganese ions. It serves as a model to split water by sunlight. Reports on the mechanism and structure of photosystem II provide a more detailed architecture of the oxygen evolving complex and the surrounding amino acids. One challenge in this field is the development of artificial model compounds to study oxygen evolution reaction outside the complicated environment of the enzyme. Calcium-manganese oxides as structural and functional models for the active site of photosystem II are explained and reviewed in this paper. Because of related structures of these calcium-manganese oxides and the catalytic centers of active site of the oxygen evolving complex of photosystem II, the study may help to understand more about mechanism of oxygen evolution by the oxygen evolving complex of photosystem II. Copyright © 2010 Elsevier B.V. All rights reserved.

The Ottawa panel clinical practice guidelines for the management of knee osteoarthritis. Part one: introduction, and mind-body exercise programs.

PubMed

Brosseau, Lucie; Taki, Jade; Desjardins, Brigit; Thevenot, Odette; Fransen, Marlene; Wells, George A; Imoto, Aline Mizusaki; Toupin-April, Karine; Westby, Marie; Gallardo, Inmaculada C Álvarez; Gifford, Wendy; Laferrière, Lucie; Rahman, Prinon; Loew, Laurianne; Angelis, Gino De; Cavallo, Sabrina; Shallwani, Shirin Mehdi; Aburub, Ala'; Bennell, Kim L; Van der Esch, Martin; Simic, Milena; McConnell, Sara; Harmer, Alison; Kenny, Glen P; Paterson, Gail; Regnaux, Jean-Philippe; Lefevre-Colau, Marie-Martine; McLean, Linda

2017-05-01

To identify effective mind-body exercise programs and provide clinicians and patients with updated, high-quality recommendations concerning non-traditional land-based exercises for knee osteoarthritis. A systematic search and adapted selection criteria included comparative controlled trials with mind-body exercise programs for patients with knee osteoarthritis. A panel of experts reached consensus on the recommendations using a Delphi survey. A hierarchical alphabetical grading system (A, B, C+, C, D, D+, D-) was used, based on statistical significance ( P < 0.5) and clinical importance (⩾15% improvement). The four high-quality studies identified demonstrated that various mind-body exercise programs are promising for improving the management of knee osteoarthritis. Hatha Yoga demonstrated significant improvement for pain relief (Grade B) and physical function (Grade C+). Tai Chi Qigong demonstrated significant improvement for quality of life (Grade B), pain relief (Grade C+) and physical function (Grade C+). Sun style Tai Chi gave significant improvement for pain relief (Grade B) and physical function (Grade B). Mind-body exercises are promising approaches to reduce pain, as well as to improve physical function and quality of life for individuals with knee osteoarthritis.

Expression of TRPV1 channels by Cajal-Retzius cells and layer-specific modulation of synaptic transmission by capsaicin in the mouse hippocampus.

PubMed

Anstötz, Max; Lee, Sun Kyong; Maccaferri, Gianmaria

2018-05-28

By taking advantage of calcium imaging and electrophysiology, we provide direct pharmacological evidence for the functional expression of TRPV1 channels in hippocampal Cajal-Retzius cells. Application of the TRPV1 activator capsaicin powerfully enhances spontaneous synaptic transmission in the hippocampal layers that are innervated by the axons of Cajal-Retzius cells. Capsaicin-triggered calcium responses and membrane currents in Cajal-Retzius cells, as well as layer-specific modulation of spontaneous synaptic transmission, are absent when the drug is applied to slices prepared from TRPV1 - / - animals. We discuss the implications of the functional expression of TRPV1 channels in Cajal-Retzius cells and of the observed TRPV1-dependent layer-specific modulation of synaptic transmission for physiological and pathological network processing. The vanilloid receptor TRPV1 forms complex polymodal channels that are expressed by sensory neurons and play a critical role in nociception. Their distribution pattern and functions in cortical circuits are, however, much less understood. Although TRPV1 reporter mice have suggested that, in the hippocampus, TRPV1 is predominantly expressed by Cajal-Retzius cells (CRs), direct functional evidence is missing. As CRs powerfully excite GABAergic interneurons of the molecular layers, TRPV1 could play important roles in the regulation of layer-specific processing. Here, we have taken advantage of calcium imaging with the genetically encoded indicator GCaMP6s and patch-clamp techniques to study the responses of hippocampal CRs to the activation of TRPV1 by capsaicin, and have compared the effect of TRPV1 stimulation on synaptic transmission in layers innervated or non-innervated by CRs. Capsaicin induced both calcium responses and membrane currents in ∼50% of the cell tested. Neither increases of intracellular calcium nor whole-cell currents were observed in the presence of the TRPV1 antagonists capsazepine/Ruthenium Red or in slices prepared from TRPV1 knockout mice. We also report a powerful TRPV1-dependent enhancement of spontaneous synaptic transmission onto interneurons with dendritic trees confined to the layers innervated by CRs. In conclusion, our work establishes that functional TRPV1 is expressed by a significant fraction of CRs and we propose that TRPV1 activity may regulate layer-specific synaptic transmission in the hippocampus. Lastly, as CR density decreases during postnatal development, we also propose that functional TRPV1 receptors may be related to mechanisms involved in CR progressive reduction by calcium-dependent toxicity/apoptosis. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Recovery of high purity phosphorus from municipal wastewater secondary effluent by a high-speed adsorbent.

PubMed

Midorikawa, I; Aoki, H; Omori, A; Shimizu, T; Kawaguchi, Y; Kassai, K; Murakami, T

2008-01-01

High purity phosphorus was recovered from municipal wastewater secondary effluent as phosphate, using a newly developed phosphorus adsorption and recovery system. A high-speed adsorbent having a unique porous structure was used in this system. The secondary effluent, showing total phosphorus (TP) of 0.1-2.1 mg P/L, was passed through an adsorbent packed column at high space velocity (SV) of 15 h(-1). The TP of the treated water was as low as 0.02-0.04 mg P/L, indicating that 97% of phosphorus in the secondary effluent was removed. The removed phosphorus was desorbed from the adsorbent by passing a sodium hydroxide aqueous solution through the column. Calcium hydroxide was added to this solution to precipitate the phosphorus as calcium phosphate. This precipitate was neutralized with hydrochloric acid aqueous solution, washed with water, and then solid-liquid separation was performed for the phosphorus recovery. The main constituent of the recovered phosphorus was apatite-type calcium phosphate, with 16% phosphorus content, which matched that of high-grade phosphorus ore. The hazardous elements content of the recovered phosphorus was exceedingly low. Therefore the recovered phosphorus can be applied to an alternative for phosphorus ore, or to a phosphate fertilizer. IWA Publishing 2008.

Retention and release of oil-in-water emulsions from filled hydrogel beads composed of calcium alginate: impact of emulsifier type and pH.

PubMed

Zeeb, Benjamin; Saberi, Amir Hossein; Weiss, Jochen; McClements, David Julian

2015-03-21

Delivery systems based on filled hydrogel particles (microgels) can be fabricated from natural food-grade lipids and biopolymers. The potential for controlling release characteristics by modulating the electrostatic interactions between emulsifier-coated lipid droplets and the biopolymer matrix within hydrogel particles was investigated. A multistage procedure was used to fabricate calcium alginate beads filled with lipid droplets stabilized by non-ionic, cationic, anionic, or zwitterionic emulsifiers. Oil-in-water emulsions stabilized by Tween 60, DTAB, SDS, or whey protein were prepared by microfluidization, mixed with various alginate solutions, and then microgels were formed by simple extrusion into calcium solutions. The microgels were placed into a series of buffer solutions with different pH values (2 to 11). Lipid droplets remained encapsulated under acidic and neutral conditions, but were released under highly basic conditions (pH 11) due to hydrogel swelling when the alginate concentration was sufficiently high. Lipid droplet release increased with decreasing alginate concentration, which could be attributed to an increase in the pore size of the hydrogel matrix. These results have important implications for the design of delivery systems to entrap and control the release of lipophilic bioactive components within filled hydrogel particles.

Whole-Volume Clustering of Time Series Data from Zebrafish Brain Calcium Images via Mixture Modeling.

PubMed

Nguyen, Hien D; Ullmann, Jeremy F P; McLachlan, Geoffrey J; Voleti, Venkatakaushik; Li, Wenze; Hillman, Elizabeth M C; Reutens, David C; Janke, Andrew L

2018-02-01

Calcium is a ubiquitous messenger in neural signaling events. An increasing number of techniques are enabling visualization of neurological activity in animal models via luminescent proteins that bind to calcium ions. These techniques generate large volumes of spatially correlated time series. A model-based functional data analysis methodology via Gaussian mixtures is suggested for the clustering of data from such visualizations is proposed. The methodology is theoretically justified and a computationally efficient approach to estimation is suggested. An example analysis of a zebrafish imaging experiment is presented.

Hypothalamic involvement in stress-induced hypocalcemia in rats.

PubMed

Aou, S; Ma, J; Hori, T

1993-08-20

Although hormonal regulation of blood calcium homeostasis has been intensively investigated in the peripheral organs, the involvement of the central nervous system in calcium regulation is still poorly understood. In the present study, we found that (1) bilateral lesions of the ventromedial nucleus of the hypothalamus (VMH), but not those of the paraventricular hypothalamic nucleus or the lateral hypothalamic area, eliminated immobilization (IMB)-induced hypocalcemia, and (2) electrical stimulation of the VMH decreased the blood calcium level. The results suggest that the VMH has a hypocalcemic function and plays a role in IMB-induced hypocalcemia.

Nuclear Calcium Buffering Capacity Shapes Neuronal Architecture*

PubMed Central

Mauceri, Daniela; Hagenston, Anna M.; Schramm, Kathrin; Weiss, Ursula; Bading, Hilmar

2015-01-01

Calcium-binding proteins (CaBPs) such as parvalbumin are part of the cellular calcium buffering system that determines intracellular calcium diffusion and influences the spatiotemporal dynamics of calcium signals. In neurons, CaBPs are primarily localized to the cytosol and function, for example, in nerve terminals in short-term synaptic plasticity. However, CaBPs are also expressed in the cell nucleus, suggesting that they modulate nuclear calcium signals, which are key regulators of neuronal gene expression. Here we show that the calcium buffering capacity of the cell nucleus in mouse hippocampal neurons regulates neuronal architecture by modulating the expression levels of VEGFD and the complement factor C1q-c, two nuclear calcium-regulated genes that control dendrite geometry and spine density, respectively. Increasing the levels of nuclear calcium buffers by means of expression of a nuclearly targeted form of parvalbumin fused to mCherry (PV.NLS-mC) led to a reduction in VEGFD expression and, as a result, to a decrease in total dendritic length and complexity. In contrast, mRNA levels of the synapse pruning factor C1q-c were increased in neurons expressing PV.NLS-mC, causing a reduction in the density and size of dendritic spines. Our results establish a close link between nuclear calcium buffering capacity and the transcription of genes that determine neuronal structure. They suggest that the development of cognitive deficits observed in neurological conditions associated with CaBP deregulation may reflect the loss of necessary structural features of dendrites and spines. PMID:26231212

Functional domains of plant chimeric calcium/calmodulin-dependent protein kinase: regulation by autoinhibitory and visinin-like domains

NASA Technical Reports Server (NTRS)

Ramachandiran, S.; Takezawa, D.; Wang, W.; Poovaiah, B. W.

1997-01-01

A novel calcium-binding calcium/calmodulin-dependent protein kinase (CCaMK) with a catalytic domain, calmodulin-binding domain, and a neural visinin-like domain was cloned and characterized from plants [Patil et al., (1995) Proc. Natl. Acad. Sci. USA 92, 4797-4801; Takezawa et al. (1996) J. Biol. Chem. 271, 8126-8132]. The mechanisms of CCaMK activation by calcium and calcium/calmodulin were investigated using various deletion mutants. The use of deletion mutants of CCaMK lacking either one, two, or all three calcium-binding EF hands indicated that all three calcium-binding sites in the visinin-like domain were crucial for the full calcium/calmodulin-dependent kinase activity. As each calcium-binding EF hand was deleted, there was a gradual reduction in calcium/calmodulin-dependent kinase activity from 100 to 4%. Another mutant (amino acids 1-322) which lacks both the visinin-like domain containing three EF hands and the calmodulin-binding domain was constitutively active, indicating the presence of an autoinhibitory domain around the calmodulin-binding domain. By using various synthetic peptides and the constitutively active mutant, we have shown that CCaMK contains an autoinhibitory domain within the residues 322-340 which overlaps its calmodulin-binding domain. Kinetic studies with both ATP and the GS peptide substrate suggest that the autoinhibitory domain of CCaMK interacts only with the peptide substrate binding motif of the catalytic domain, but not with the ATP-binding motif.

Unexpected link between polyketide synthase and calcium carbonate biomineralization.

PubMed

Hojo, Motoki; Omi, Ai; Hamanaka, Gen; Shindo, Kazutoshi; Shimada, Atsuko; Kondo, Mariko; Narita, Takanori; Kiyomoto, Masato; Katsuyama, Yohei; Ohnishi, Yasuo; Irie, Naoki; Takeda, Hiroyuki

2015-01-01

Calcium carbonate biominerals participate in diverse physiological functions. Despite intensive studies, little is known about how mineralization is initiated in organisms. We analyzed the medaka spontaneous mutant, ha, defective in otolith (calcareous ear stone) formation. ha lacks a trigger for otolith mineralization, and the causative gene was found to encode polyketide synthase (pks), a multifunctional enzyme mainly found in bacteria, fungi, and plant. Subsequent experiments demonstrate that the products of medaka PKS, most likely polyketides or their derivatives, act as nucleation facilitators in otolith mineralization. The generality of this novel PKS function is supported by the essential role of echinoderm PKS in calcareous skeleton formation together with the presence of PKSs in a much wider range of animals from coral to vertebrates. The present study first links PKS to biomineralization and provides a genetic cue for biogeochemistry of carbon and calcium cycles.

Ballistic delivery of dyes for structural and functional studies of the nervous system

PubMed Central

Gan, Wen-Biao; Grutzendler, Jaime; Wong, Rachel O.; Lichtman, Jeff W.

2010-01-01

This chapter describes a detail protocol for rapid labeling of cells in a variety of preparations by means of particle-mediated ballistic (gene gun) delivery of fluorescent dyes. This method has been used for rapid labeling of cells with either lipid or water-soluble dyes in a variety of preparations. In particular, carbocyanine lipophilic dyes such as DiI have been used to obtain Golgi-like labeling of neurons and glia in fixed and live cell cultures, brain slices, as well as fixed post-mortem human brain. Water-soluble calcium indicators such as calcium green-1 dextran have been used to image calcium dynamics in living brain slices and retinal explants. This ballistic labeling technique is thus useful for studying the structure and function of neurons and glia in both living and fixed specimens. PMID:20147144

L-Type Calcium Channels Modulation by Estradiol.

PubMed

Vega-Vela, Nelson E; Osorio, Daniel; Avila-Rodriguez, Marco; Gonzalez, Janneth; García-Segura, Luis Miguel; Echeverria, Valentina; Barreto, George E

2017-09-01

Voltage-gated calcium channels are key regulators of brain function, and their dysfunction has been associated with multiple conditions and neurodegenerative diseases because they couple membrane depolarization to the influx of calcium-and other processes such as gene expression-in excitable cells. L-type calcium channels, one of the three major classes and probably the best characterized of the voltage-gated calcium channels, act as an essential calcium binding proteins with a significant biological relevance. It is well known that estradiol can activate rapidly brain signaling pathways and modulatory/regulatory proteins through non-genomic (or non-transcriptional) mechanisms, which lead to an increase of intracellular calcium that activate multiple kinases and signaling cascades, in the same way as L-type calcium channels responses. In this context, estrogens-L-type calcium channels signaling raises intracellular calcium levels and activates the same signaling cascades in the brain probably through estrogen receptor-independent modulatory mechanisms. In this review, we discuss the available literature on this area, which seems to suggest that estradiol exerts dual effects/modulation on these channels in a concentration-dependent manner (as a potentiator of these channels in pM concentrations and as an inhibitor in nM concentrations). Indeed, estradiol may orchestrate multiple neurotrophic responses, which open a new avenue for the development of novel estrogen-based therapies to alleviate different neuropathologies. We also highlight that it is essential to determine through computational and/or experimental approaches the interaction between estradiol and L-type calcium channels to assist these developments, which is an interesting area of research that deserves a closer look in future biomedical research.

Biochemical investigations and mapping of the calcium-binding sites of heparinase I from Flavobacterium heparinum.

PubMed

Shriver, Z; Liu, D; Hu, Y; Sasisekharan, R

1999-02-12

The heparinases from Flavobacterium heparinum are lyases that specifically cleave heparin-like glycosaminoglycans. Previously, amino acids located in the active site of heparinase I have been identified and mapped. In an effort to further understand the mechanism by which heparinase I cleaves its polymer substrate, we sought to understand the role of calcium, as a necessary cofactor, in the enzymatic activity of heparinase I. Specifically, we undertook a series of biochemical and biophysical experiments to answer the question of whether heparinase I binds to calcium and, if so, which regions of the protein are involved in calcium binding. Using the fluorescent calcium analog terbium, we found that heparinase I tightly bound divalent and trivalent cations. Furthermore, we established that this interaction was specific for ions that closely approximate the ionic radius of calcium. Through the use of the modification reagents N-ethyl-5-phenylisoxazolium-3'-sulfonate (Woodward's reagent K) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, we showed that the interaction between heparinase I and calcium was essential for proper functioning of the enzyme. Preincubation with either calcium alone or calcium in the presence of heparin was able to protect the enzyme from inactivation by these modifying reagents. In addition, through mapping studies of Woodward's reagent K-modified heparinase I, we identified two putative calcium-binding sites, CB-1 (Glu207-Ala219) and CB-2 (Thr373-Arg384), in heparinase I that not only are specifically modified by Woodward's reagent K, leading to loss of enzymatic activity, but also conform to the calcium-coordinating consensus motif.

Fructo-oligosaccharides and calcium absorption and retention in adolescent girls.

PubMed

Martin, Berdine R; Braun, Michelle M; Wigertz, Karin; Bryant, Rebecca; Zhao, Yongdong; Lee, WangHee; Kempa-Steczko, Ania; Weaver, Connie M

2010-08-01

Several studies have shown a positive effect of fructo-oligosaccharides on calcium absorption and retention in animals and humans. Effects of levels of these pre-biotics that can be functionally incorporated into manufactured foods, have not been studied in controlled feeding studies. This study was designed to evaluate the effect of 9 g/d of fructo-oligosaccharides as part of a controlled diet on calcium absorption and retention in adolescent girls. Fourteen healthy adolescent girls aged 11-13 y were studied in a metabolic setting for two 3-week periods separated by a 2-week washout period. In a randomized, double-blinded, crossover design, the teens received a diet containing either 9 g/d oligofructose-enriched inulin in a calcium-fortified cereal or the control cereal with no inulin. Both diets contained ~1500 mg calcium daily. Calcium retention was determined on the third week of each period. On day 14 of the diet period, fractional calcium absorption was determined from the enrichment of (44)Ca in 4-day urine collections. Calcium absorption (67 ± 3 vs. 66 ± 3%) and retention (409 ± 394 vs. 464 ± 241 mg/d) were not significantly different when diets contained 9 g/d oligofructose-enriched inulin or not in a calcium-fortified cereal. Daily consumption of cereal containing a combination of short- and long-chain fructo-oligosaccharides as part of a controlled diet did not benefit calcium absorption or retention in adolescent girls. Lack of response to the prebiotic in this cohort may relate to their already high calcium absorption efficiency.

A Specific Peptide with Calcium-Binding Capacity from Defatted Schizochytrium sp. Protein Hydrolysates and the Molecular Properties.

PubMed

Cai, Xixi; Yang, Qian; Lin, Jiaping; Fu, Nanyan; Wang, Shaoyun

2017-03-29

Marine microorganisms have been proposed as a new kind of protein source. Efforts are needed in order to transform the protein-rich biological wastes left after lipid extraction into value-added bio-products. Thus, the utilization of protein recovered from defatted Schizochytrium sp. by-products presents an opportunity. A specific peptide Tyr-Leu (YL) with calcium-binding capacity was purified from defatted Schizochytrium sp. protein hydrolysates through gel filtration chromatography and RP-HPLC. The calcium-binding activity of YL reached 126.34 ± 3.40 μg/mg. The calcium-binding mechanism was investigated through ultraviolet, fluorescence and infrared spectroscopy. The results showed that calcium ions could form dative bonds with carboxyl oxygen atoms and amino nitrogen atoms as well as the nitrogen and oxygen atoms of amide bonds. YL-Ca exhibited excellent thermal stability and solubility, which was beneficial for its absorption and transport in the basic intestinal tract of the human body. Moreover, the cellular uptake of calcium in Caco-2 cells showed that YL-Ca could enhance calcium uptake efficiency and protect calcium ions against precipitation caused by dietary inhibitors such as tannic acid, oxalate, phytate and metal ions. The findings indicate that the by-product of Schizochytrium sp. is a promising source for making peptide-calcium bio-products as algae-based functional supplements for human beings.

Isolation, characterization and immunolocalization of a seed dominant CaM from finger millet (Eleusine coracana L. Gartn.) for studying its functional role in differential accumulation of calcium in developing grains.

PubMed

Kumar, Anil; Mirza, Neelofar; Charan, Tara; Sharma, Netrapal; Gaur, Vikram Singh

2014-03-01

To understand the exceptional high grain calcium accumulation in finger millet grains, a calmodulin (CaM) gene that is strongly expressed during developing spikes of high grain calcium genotype was further characterized. Using 5'-3' RACE, the full-length CaM open reading frame (ORF) was isolated and the deduced protein sequence showed the presence of four characteristic EF motifs. Phylogenetic analysis showed that the finger millet CaM (Eleusine coracana calmodulin [EcCaM]) was identical to the rice CaM 1-1. Southern hybridization showed the presence of at least four copies of CaM gene that might be located on different regions of the finger millet "AABB" genome. Immunodetection using monospecific polyclonal anti-EcCaM antibodies revealed that EcCaM is localized in the embryo and aleurone layer and accumulates in higher amounts in high grain calcium genotype compared to the low grain calcium genotype. Furthermore, in silico analysis showed that EcCaM interacts with aquaporin which indicates that calcium is probably delivered to developing spike via mass flow of water. These results indicate that higher expression of CaM might cause greater stimulation of the downstream calcium transport machinery operative in the aleurone layer leading to the higher calcium accumulation in the grains of high grain calcium genotype.

The impact of mitochondrial endosymbiosis on the evolution of calcium signaling.

PubMed

Blackstone, Neil W

2015-03-01

At high concentrations, calcium has detrimental effects on biological systems. Life likely arose in a low calcium environment, and the first cells evolved mechanisms to maintain this environment internally. Bursts of calcium influx followed by efflux or sequestration thus developed in a functional context. For example, in proto-cells with exterior energy-converting membranes, such bursts could be used to depolarize the membrane. In this way, proto-cells could maintain maximal phosphorylation (metabolic state 3) and moderate levels of reactive oxygen species (ROS), while avoiding the resting state (metabolic state 4) and high levels of ROS. This trait is likely a shared primitive characteristic of prokaryotes. When eukaryotes evolved, the α-proteobacteria that gave rise to proto-mitochondria inhabited a novel environment, the interior of the proto-eukaryote that had a low calcium concentration. In this environment, metabolic homeostasis was difficult to maintain, and there were inherent risks from ROS, yet depolarizing the proto-mitochondrial membrane by calcium influx was challenging. To maintain metabolic state 3, proto-mitochondria were required to congregate near calcium influx points in the proto-eukaryotic membrane. This behavior, resulting in embryonic forms of calcium signaling, may have occurred immediately after the initiation of the endosymbiosis. Along with ROS, calcium may have served as one of the key forms of crosstalk among the community of prokaryotes that led to the eukaryotic cell. Copyright © 2014 Elsevier Ltd. All rights reserved.

Enlargement of Ribbons in Zebrafish Hair Cells Increases Calcium Currents But Disrupts Afferent Spontaneous Activity and Timing of Stimulus Onset

PubMed Central

Schreck, Mary; Petralia, Ronald S.; Wang, Ya-Xian; Zhang, Qiuxiang

2017-01-01

In sensory hair cells of auditory and vestibular organs, the ribbon synapse is required for the precise encoding of a wide range of complex stimuli. Hair cells have a unique presynaptic structure, the synaptic ribbon, which organizes both synaptic vesicles and calcium channels at the active zone. Previous work has shown that hair-cell ribbon size is correlated with differences in postsynaptic activity. However, additional variability in postsynapse size presents a challenge to determining the specific role of ribbon size in sensory encoding. To selectively assess the impact of ribbon size on synapse function, we examined hair cells in transgenic zebrafish that have enlarged ribbons, without postsynaptic alterations. Morphologically, we found that enlarged ribbons had more associated vesicles and reduced presynaptic calcium-channel clustering. Functionally, hair cells with enlarged ribbons had larger global and ribbon-localized calcium currents. Afferent neuron recordings revealed that hair cells with enlarged ribbons resulted in reduced spontaneous spike rates. Additionally, despite larger presynaptic calcium signals, we observed fewer evoked spikes with longer latencies from stimulus onset. Together, our work indicates that hair-cell ribbon size influences the spontaneous spiking and the precise encoding of stimulus onset in afferent neurons. SIGNIFICANCE STATEMENT Numerous studies support that hair-cell ribbon size corresponds with functional sensitivity differences in afferent neurons and, in the case of inner hair cells of the cochlea, vulnerability to damage from noise trauma. Yet it is unclear whether ribbon size directly influences sensory encoding. Our study reveals that ribbon enlargement results in increased ribbon-localized calcium signals, yet reduces afferent spontaneous activity and disrupts the timing of stimulus onset, a distinct aspect of auditory and vestibular encoding. These observations suggest that varying ribbon size alone can influence sensory encoding, and give further insight into how hair cells transduce signals that cover a wide dynamic range of stimuli. PMID:28546313

Deficits in memory and hippocampal long-term potentiation in mice with reduced calbindin D28K expression.

PubMed Central

Molinari, S; Battini, R; Ferrari, S; Pozzi, L; Killcross, A S; Robbins, T W; Jouvenceau, A; Billard, J M; Dutar, P; Lamour, Y; Baker, W A; Cox, H; Emson, P C

1996-01-01

The influx of calcium into the postsynaptic neuron is likely to be an important event in memory formation. Among the mechanisms that nerve cells may use to alter the time course or size of a spike of intracellular calcium are cytosolic calcium binding or "buffering" proteins. To consider the role in memory formation of one of these proteins, calbindin D28K, which is abundant in many neurons, including the CA1 pyramidal cells of the hippocampus, transgenic mice deficient in calbindin D28K have been created. These mice show selective impairments in spatial learning paradigms and fail to maintain long-term potentiation. These results suggest a role for calbindin D28K protein in temporally extending a neuronal calcium signal, allowing the activation of calcium-dependent intracellular signaling pathways underlying memory function. Images Fig. 1 PMID:8755597

[Myofibroblasts and afferent signalling in the urinary bladder. A concept].

PubMed

Neuhaus, J; Scholler, U; Freick, K; Schwalenberg, T; Heinrich, M; Horn, L C; Stolzenburg, J U

2008-09-01

Afferent signal transduction in the urinary bladder is still not clearly understood. An increasing body of evidence supports the view of complex interactions between urothelium, suburothelial myofibroblasts, and sensory nerves. Bladder tissue from tumour patients was used in this study. Methods included confocal immunofluorescence, polymerase chain reaction, calcium imaging, and fluorescence recovery after photobleaching (FRAP).Myofibroblasts express muscarinic and purinergic receptors. They show constitutive spontaneous activity in calcium imaging, which completely depends on extracellular calcium. Stimulation with carbachol and ATP-evoked intracellular calcium transients also depend on extracellular calcium. The intensive coupling between the cells is significantly diminished by incubation with TGF-beta 1. Myofibroblasts form an important cellular element within the afferent signalling of the urinary bladder. They possess all features required to take part in the complex interactions with urothelial cells and sensory nerves. Modulation of their function by cytokines may provide a pathomechanism for bladder dysfunction.

Investigation of calcium-dependent activity and conformational dynamics of zebra fish 12-lipoxygenase.

PubMed

Mittal, Monica; Hasan, Mahmudul; Balagunaseelan, Navisraj; Fauland, Alexander; Wheelock, Craig; Rådmark, Olof; Haeggström, Jesper Z; Rinaldo-Matthis, Agnes

2017-08-01

A 12-lipoxygenase in zebra fish (zf12-LOX) was found to be required for normal embryonic development and LOXs are of great interest for targeted drug designing. In this study, we investigate the structural-functional aspects of zf12-LOX in response to calcium. A soluble version of zf12-LOX was created by mutagenesis. Based on multiple sequence alignment, we mutated the putative calcium-responsive amino acids in N-PLAT domain of soluble zf12-LOX. Using a series of biophysical methods, we ascertained the oligomeric state, stability, structural integrity and conformational changes of zf12-LOX in response to calcium. We also compared the biophysical properties of soluble zf12-LOX with the mutant in the absence and presence of calcium. Here we provide a detailed characterization of soluble zf12-LOX and the mutant. Both proteins exist as compact monomers in solution, however the enzyme activity of soluble zf12-LOX is significantly increased in presence of calcium. We find that the stimulatory effect of calcium on zf12-LOX is related to a change in protein structure as observed by SAXS, adopting an open-state. In contrast, enzyme with a mutated calcium regulatory site has reduced activity-response to calcium and restricted large re-modeling, suggesting that it retains a closed-state in response to calcium. Taken together, our study suggests that Ca 2+ -dependent regulation is associated with different domain conformation(s) that might change the accessibility to substrate-binding site in response to calcium. The study can be broadly implicated in better understanding the mode(s) of action of LOXs, and the enzymes regulated by calcium in general. Copyright © 2017 Elsevier B.V. All rights reserved.

The Ottawa panel clinical practice guidelines for the management of knee osteoarthritis. Part two: strengthening exercise programs.

PubMed

Brosseau, Lucie; Taki, Jade; Desjardins, Brigit; Thevenot, Odette; Fransen, Marlene; Wells, George A; Mizusaki Imoto, Aline; Toupin-April, Karine; Westby, Marie; Álvarez Gallardo, Inmaculada C; Gifford, Wendy; Laferrière, Lucie; Rahman, Prinon; Loew, Laurianne; De Angelis, Gino; Cavallo, Sabrina; Shallwani, Shirin Mehdi; Aburub, Ala'; Bennell, Kim L; Van der Esch, Martin; Simic, Milena; McConnell, Sara; Harmer, Alison; Kenny, Glen P; Paterson, Gail; Regnaux, Jean-Philippe; Lefevre-Colau, Marie-Martine; McLean, Linda

2017-05-01

To identify effective strengthening exercise programs and provide rehabilitation teams and patients with updated, high-quality recommendations concerning traditional land-based exercises for knee osteoarthritis. A systematic search and adapted selection criteria included comparative controlled trials with strengthening exercise programs for patients with knee osteoarthritis. A panel of experts reached consensus on the recommendations using a Delphi survey. A hierarchical alphabetical grading system (A, B, C+, C, D, D+ or D-) was based on statistical significance ( p < 0.5) and clinical importance (⩾15% improvement). The 26 high-quality studies identified demonstrated that various strengthening exercise programs with/without other types of therapeutic exercises are generally effective for improving knee osteoarthritis management within a six-month period. Strengthening exercise programs demonstrated a significant improvement for pain relief (four Grade A, ten Grade B, two Grade C+), physical function (four Grade A, eight Grade B) and quality of life (three Grade B). Strengthening in combination with other types of exercises (coordination, balance, functional) showed a significant improvement in pain relief (three Grade A, 11 Grade B, eight Grade C+), physical function (two Grade A, four Grade B, three Grade C+) and quality of life (one Grade A, one Grade C+). There are a variety of choices for strengthening exercise programs with positive recommendations for healthcare professionals and knee osteoarthritis patients. There is a need to develop combined behavioral and muscle-strengthening strategies to improve long-term maintenance of regular strengthening exercise programs.

Fast Calcium Imaging with Optical Sectioning via HiLo Microscopy.

PubMed

Lauterbach, Marcel A; Ronzitti, Emiliano; Sternberg, Jenna R; Wyart, Claire; Emiliani, Valentina

2015-01-01

Imaging intracellular calcium concentration via reporters that change their fluorescence properties upon binding of calcium, referred to as calcium imaging, has revolutionized our way to probe neuronal activity non-invasively. To reach neurons densely located deep in the tissue, optical sectioning at high rate of acquisition is necessary but difficult to achieve in a cost effective manner. Here we implement an accessible solution relying on HiLo microscopy to provide robust optical sectioning with a high frame rate in vivo. We show that large calcium signals can be recorded from dense neuronal populations at high acquisition rates. We quantify the optical sectioning capabilities and demonstrate the benefits of HiLo microscopy compared to wide-field microscopy for calcium imaging and 3D reconstruction. We apply HiLo microscopy to functional calcium imaging at 100 frames per second deep in biological tissues. This approach enables us to discriminate neuronal activity of motor neurons from different depths in the spinal cord of zebrafish embryos. We observe distinct time courses of calcium signals in somata and axons. We show that our method enables to remove large fluctuations of the background fluorescence. All together our setup can be implemented to provide efficient optical sectioning in vivo at low cost on a wide range of existing microscopes.

Fast Calcium Imaging with Optical Sectioning via HiLo Microscopy

PubMed Central

Sternberg, Jenna R.; Wyart, Claire; Emiliani, Valentina

2015-01-01

Imaging intracellular calcium concentration via reporters that change their fluorescence properties upon binding of calcium, referred to as calcium imaging, has revolutionized our way to probe neuronal activity non-invasively. To reach neurons densely located deep in the tissue, optical sectioning at high rate of acquisition is necessary but difficult to achieve in a cost effective manner. Here we implement an accessible solution relying on HiLo microscopy to provide robust optical sectioning with a high frame rate in vivo. We show that large calcium signals can be recorded from dense neuronal populations at high acquisition rates. We quantify the optical sectioning capabilities and demonstrate the benefits of HiLo microscopy compared to wide-field microscopy for calcium imaging and 3D reconstruction. We apply HiLo microscopy to functional calcium imaging at 100 frames per second deep in biological tissues. This approach enables us to discriminate neuronal activity of motor neurons from different depths in the spinal cord of zebrafish embryos. We observe distinct time courses of calcium signals in somata and axons. We show that our method enables to remove large fluctuations of the background fluorescence. All together our setup can be implemented to provide efficient optical sectioning in vivo at low cost on a wide range of existing microscopes. PMID:26625116

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dag, Serkan; Yildirim, Bora; Sabuncuoglu, Baris

The objective of this study is to develop crack growth analysis methods for functionally graded materials (FGMs) subjected to mode I cyclic loading. The study presents finite elements based computational procedures for both two and three dimensional problems to examine fatigue crack growth in functionally graded materials. Developed methods allow the computation of crack length and generation of crack front profile for a graded medium subjected to fluctuating stresses. The results presented for an elliptical crack embedded in a functionally graded medium, illustrate the competing effects of ellipse aspect ratio and material property gradation on the fatigue crack growth behavior.

Functionally graded Ti6Al4V and Inconel 625 by Laser Metal Deposition

NASA Astrophysics Data System (ADS)

Pulugurtha, Syamala R.

The objective of the current work was to fabricate a crack-free functionally graded Ti6Al4V and Inconel 625 thin wall structure by Laser Metal Deposition (LMD). One potential application for the current material system is the ability to fabricate a functionally graded alloy that can be used in a space heat exchanger. The two alloys, Inconel 625 and Ti6Al4V are currently used for aerospace applications. They were chosen as candidates for grading because functionally grading those combines the properties of high strength/weight ratio of Ti6Al4V and high temperature oxidation resistance of Inconel 625 into one multifunctional material for the end application. However, there were challenges associated with the presence of Ni-Ti intermetallic phases (IMPs). The study focused on several critical areas such as (1) understanding microstructural evolution, (2) reducing macroscopic cracking, and (3) reducing mixing between graded layers. Finite element analysis (FEA) was performed to understand the effect of process conditions on multilayer claddings for simplified material systems such as SS316L and Inconel 625 where complex microstructures did not form. The thermo-mechanical models were developed using Abaqus(TM) (and some of them experimentally verified) to predict temperature-gradients; remelt layer depths and residual stresses. Microstructure evolution along the functionally graded Ti6Al4V and Inconel 625 was studied under different processing and grading conditions. Thermodynamic modeling using Factsage (v 6.1) was used to construct phase diagrams and predict the possible equilibrium major/minor phases (verified experimentally by XRD) that may be present along the functionally graded Ti6Al4V and Inconel 625 thin wall structures.

Higher-Order Theory for Functionally Graded Materials

NASA Technical Reports Server (NTRS)

Aboudi, Jacob; Pindera, Marek-Jerzy; Arnold, Steven M.

1999-01-01

This paper presents the full generalization of the Cartesian coordinate-based higher-order theory for functionally graded materials developed by the authors during the past several years. This theory circumvents the problematic use of the standard micromechanical approach, based on the concept of a representative volume element, commonly employed in the analysis of functionally graded composites by explicitly coupling the local (microstructural) and global (macrostructural) responses. The theoretical framework is based on volumetric averaging of the various field quantities, together with imposition of boundary and interfacial conditions in an average sense between the subvolumes used to characterize the composite's functionally graded microstructure. The generalization outlined herein involves extension of the theoretical framework to enable the analysis of materials characterized by spatially variable microstructures in three directions. Specialization of the generalized theoretical framework to previously published versions of the higher-order theory for materials functionally graded in one and two directions is demonstrated. In the applications part of the paper we summarize the major findings obtained with the one-directional and two-directional versions of the higher-order theory. The results illustrate both the fundamental issues related to the influence of microstructure on microscopic and macroscopic quantities governing the response of composites and the technologically important applications. A major issue addressed herein is the applicability of the classical homogenization schemes in the analysis of functionally graded materials. The technologically important applications illustrate the utility of functionally graded microstructures in tailoring the response of structural components in a variety of applications involving uniform and gradient thermomechanical loading.

Renal Control of Calcium, Phosphate, and Magnesium Homeostasis

PubMed Central

Chonchol, Michel; Levi, Moshe

2015-01-01

Calcium, phosphate, and magnesium are multivalent cations that are important for many biologic and cellular functions. The kidneys play a central role in the homeostasis of these ions. Gastrointestinal absorption is balanced by renal excretion. When body stores of these ions decline significantly, gastrointestinal absorption, bone resorption, and renal tubular reabsorption increase to normalize their levels. Renal regulation of these ions occurs through glomerular filtration and tubular reabsorption and/or secretion and is therefore an important determinant of plasma ion concentration. Under physiologic conditions, the whole body balance of calcium, phosphate, and magnesium is maintained by fine adjustments of urinary excretion to equal the net intake. This review discusses how calcium, phosphate, and magnesium are handled by the kidneys. PMID:25287933

Nanoneedle transistor-based sensors for the selective detection of intracellular calcium ions.

PubMed

Son, Donghee; Park, Sung Young; Kim, Byeongju; Koh, Jun Tae; Kim, Tae Hyun; An, Sangmin; Jang, Doyoung; Kim, Gyu Tae; Jhe, Wonho; Hong, Seunghun

2011-05-24

We developed a nanoneedle transistor-based sensor (NTS) for the selective detection of calcium ions inside a living cell. In this work, a single-walled carbon nanotube-based field effect transistor (swCNT-FET) was first fabricated at the end of a glass nanopipette and functionalized with Fluo-4-AM probe dye. The selective binding of calcium ions onto the dye molecules altered the charge state of the dye molecules, resulting in the change of the source-drain current of the swCNT-FET as well as the fluorescence intensity from the dye. We demonstrated the electrical and fluorescence detection of the concentration change of intracellular calcium ions inside a HeLa cell using the NTS.

Proton bombarded reactions of Calcium target nuclei

NASA Astrophysics Data System (ADS)

Tel, Eyyup; Sahan, Muhittin; Sarpün, Ismail Hakki; Kavun, Yusuf; Gök, Ali Armagan; Depedelen, Mesut

2017-09-01

In this study, proton bombarded nuclear reactions calculations of Calcium target nuclei have been investigated in the incident proton energy range of 1-50 MeV. The excitation functions for 40Ca target nuclei reactions have been calculated by using PCROSS nuclear reaction calculation code. Weisskopf-Ewing and the full exciton models were used for equilibrium and for pre-equilibrium calculations, respectively. The excitation functions for 40Ca target nuclei reactions (p,α), (p,n), (p,p) have been calculated using the semi-empirical formula Tel et al. [5].

Imaging auditory representations of song and syllables in populations of sensorimotor neurons essential to vocal communication.

PubMed

Peh, Wendy Y X; Roberts, Todd F; Mooney, Richard

2015-04-08

Vocal communication depends on the coordinated activity of sensorimotor neurons important to vocal perception and production. How vocalizations are represented by spatiotemporal activity patterns in these neuronal populations remains poorly understood. Here we combined intracellular recordings and two-photon calcium imaging in anesthetized adult zebra finches (Taeniopygia guttata) to examine how learned birdsong and its component syllables are represented in identified projection neurons (PNs) within HVC, a sensorimotor region important for song perception and production. These experiments show that neighboring HVC PNs can respond at markedly different times to song playback and that different syllables activate spatially intermingled PNs within a local (~100 μm) region of HVC. Moreover, noise correlations were stronger between PNs that responded most strongly to the same syllable and were spatially graded within and between classes of PNs. These findings support a model in which syllabic and temporal features of song are represented by spatially intermingled PNs functionally organized into cell- and syllable-type networks within local spatial scales in HVC. Copyright © 2015 the authors 0270-6474/15/355589-17$15.00/0.

Amelioration of estrogen-deficiency-induced obesity by Ocimum gratissimum

PubMed Central

Chao, Pei-Yu; Chiang, Tsay-I; Chang, I-Chang; Tsai, Fang-Ling; Lee, Hsueh-Hui; Hsieh, Kuanghui; Chiu, Yung-Wei; Lai, Te-Jen; Liu, Jer-Yuh; Hsu, Li-Sung; Shih, Yang-Chia

2017-01-01

Objectives: Menopausal transition in women initiates with declining estrogen levels and is followed by significant changes in their physiological characteristics. These changes often lead to medical conditions, such as obesity, which is correlated with chronic low-grade/subclinical inflammation. Ocimum gratissimum L. is a food spice or traditional herb in many countries; the plant is rich in antioxidants, which possess anti-inflammation activities and multitude of other therapeutic functions. Methods: In this study, we evaluated effects of O. gratissimum extract (OGE) in preventing obesity by using ovariectomized (OVX) animal models to mimic menopausal women. Methods: OVX rats showed increase in body weight and in adipocyte size in perigonadal adipose tissue (p <0.05) and decrease in uterus weight. By contrast, OGE (0.2 mg/ml) significantly reduced body weight gain and adipocyte in OVX rats and showed insignificant changes in uterus weight. Further investigation indicated that OGE exerted no influence on levels of dorsal fat, serum total cholesterol, and serum triacylglycerol and on serum biochemical factors, calcium, phosphorus, and glucose. Conclusion: These findings suggested that OGE dietary supplements may be useful in controlling body weight of menopausal women. PMID:28824328

[Primary esophageal motility disorders; especially about esophageal achalasia].

PubMed

Miyazaki, Tatsuya; Sohda, Makoto; Sakai, Makoto; Tanaka, Naritaka; Suzuki, Shigemasa; Yokobori, Takehiko; Inose, Takanori; Nakajima, Masanobu; Fukuchi, Minoru; Kato, Hiroyuki; Kusano, Motoyasu; Kuwano, Hiroyuki

2011-07-01

Esophageal motility disorders are classified primary and secondary, and primary esophageal motility disorders are classified esophageal achalasia and other diseases by manometry. An esophageal emptying disorder associated with insufficient relaxation of the lower esophageal sphincter (LES) and elimination of peristaltic waves on the esophageal body is the major abnormality of achalasia. Esophagogram, endoscopy, and manometry are used for diagnosis. As pharmacological therapy, administration of a calcium channel blocker or nitrate is useful. The pharmacological therapy is not recommended as long-term basic therapy but as a temporary treatment. At 1st, the balloon dilation method is chosen in treatment of achalasia Surgical treatment is indicated in the following cases: (1) Patients uneffected by balloon dilation, (2) Flask type with grade II to III dilation, and sigmoid type, (3) the gradual progression to the pathophysiological stage, (4) young patients, (5) complicated with esophageal cancer. Laparoscopic Heller-Dor procedure is the most popular surgical procedure, recently. It is somewhat difficult to perform surgical treatment for this functional disease. We should select the most suitable individualized treatment with efficient comprehension of the pathophysiological situation.

Amelioration of estrogen-deficiency-induced obesity by Ocimum gratissimum.

PubMed

Chao, Pei-Yu; Chiang, Tsay-I; Chang, I-Chang; Tsai, Fang-Ling; Lee, Hsueh-Hui; Hsieh, Kuanghui; Chiu, Yung-Wei; Lai, Te-Jen; Liu, Jer-Yuh; Hsu, Li-Sung; Shih, Yang-Chia

2017-01-01

Objectives: Menopausal transition in women initiates with declining estrogen levels and is followed by significant changes in their physiological characteristics. These changes often lead to medical conditions, such as obesity, which is correlated with chronic low-grade/subclinical inflammation. Ocimum gratissimum L. is a food spice or traditional herb in many countries; the plant is rich in antioxidants, which possess anti-inflammation activities and multitude of other therapeutic functions. Methods: In this study, we evaluated effects of O . gratissimum extract (OGE) in preventing obesity by using ovariectomized (OVX) animal models to mimic menopausal women. Methods: OVX rats showed increase in body weight and in adipocyte size in perigonadal adipose tissue ( p <0.05) and decrease in uterus weight. By contrast, OGE (0.2 mg/ml) significantly reduced body weight gain and adipocyte in OVX rats and showed insignificant changes in uterus weight. Further investigation indicated that OGE exerted no influence on levels of dorsal fat, serum total cholesterol, and serum triacylglycerol and on serum biochemical factors, calcium, phosphorus, and glucose. Conclusion: These findings suggested that OGE dietary supplements may be useful in controlling body weight of menopausal women.

Production and purification of lentiviral vectors generated in 293T suspension cells with baculoviral vectors.

PubMed

Lesch, H P; Laitinen, A; Peixoto, C; Vicente, T; Makkonen, K-E; Laitinen, L; Pikkarainen, J T; Samaranayake, H; Alves, P M; Carrondo, M J T; Ylä-Herttuala, S; Airenne, K J

2011-06-01

Lentivirus can be engineered to be a highly potent vector for gene therapy applications. However, generation of clinical grade vectors in enough quantities for therapeutic use is still troublesome and limits the preclinical and clinical experiments. As a first step to solve this unmet need we recently introduced a baculovirus-based production system for lentiviral vector (LV) production using adherent cells. Herein, we have adapted and optimized the production of these vectors to a suspension cell culture system using recombinant baculoviruses delivering all elements required for a safe latest generation LV preparation. High-titer LV stocks were achieved in 293T cells grown in suspension. Produced viruses were accurately characterized and the functionality was also tested in vivo. Produced viruses were compared with viruses produced by calcium phosphate transfection method in adherent cells and polyethylenimine transfection method in suspension cells. Furthermore, a scalable and cost-effective capture purification step was developed based on a diethylaminoethyl monolithic column capable of removing most of the baculoviruses from the LV pool with 65% recovery.

Aeroelastic Tailoring of a Plate Wing with Functionally Graded Materials

NASA Technical Reports Server (NTRS)

Dunning, Peter D.; Stanford, Bret K.; Kim, H. Alicia; Jutte, Christine V.

2014-01-01

This work explores the use of functionally graded materials for the aeroelastic tailoring of a metallic cantilevered plate-like wing. Pareto trade-off curves between dynamic stability (flutter) and static aeroelastic stresses are obtained for a variety of grading strategies. A key comparison is between the effectiveness of material grading, geometric grading (i.e., plate thickness variations), and using both simultaneously. The introduction of material grading does, in some cases, improve the aeroelastic performance. This improvement, and the physical mechanism upon which it is based, depends on numerous factors: the two sets of metallic material parameters used for grading, the sweep of the plate, the aspect ratio of the plate, and whether the material is graded continuously or discretely.

Domain General Mediators of the Relation between Kindergarten Number Sense and First-Grade Mathematics Achievement

PubMed Central

Hassinger-Das, Brenna; Jordan, Nancy C.; Glutting, Joseph; Irwin, Casey; Dyson, Nancy

2013-01-01

Domain general skills that mediate the relation between kindergarten number sense and first-grade mathematics skills were investigated. Participants were 107 children who displayed low number sense in the fall of kindergarten. Controlling for background variables, multiple regression analyses showed that attention problems and executive functioning both were unique predictors of mathematics outcomes. Attention problems were more important for predicting first-grade calculation performance while executive functioning was more important for predicting first-grade performance on applied problems. Moreover, both executive functioning and attention problems were unique partial mediators of the relationship between kindergarten and first-grade mathematics skills. The results provide empirical support for developing interventions that target executive functioning and attention problems in addition to instruction in number skills for kindergartners with initial low number sense. PMID:24237789

Domain-general mediators of the relation between kindergarten number sense and first-grade mathematics achievement.

PubMed

Hassinger-Das, Brenna; Jordan, Nancy C; Glutting, Joseph; Irwin, Casey; Dyson, Nancy

2014-02-01

Domain-general skills that mediate the relation between kindergarten number sense and first-grade mathematics skills were investigated. Participants were 107 children who displayed low number sense in the fall of kindergarten. Controlling for background variables, multiple regression analyses showed that both attention problems and executive functioning were unique predictors of mathematics outcomes. Attention problems were more important for predicting first-grade calculation performance, whereas executive functioning was more important for predicting first-grade performance on applied problems. Moreover, both executive functioning and attention problems were unique partial mediators of the relationship between kindergarten and first-grade mathematics skills. The results provide empirical support for developing interventions that target executive functioning and attention problems in addition to instruction in number skills for kindergartners with initial low number sense. Copyright © 2013 Elsevier Inc. All rights reserved.

Protein arginine deiminase 2 binds calcium in an ordered fashion: Implications for inhibitor design

DOE PAGES

Slade, Daniel J.; Fang, Pengfei; Dreyton, Christina J.; ...

2015-01-26

Protein arginine deiminases (PADs) are calcium-dependent histone-modifying enzymes whose activity is dysregulated in inflammatory diseases and cancer. PAD2 functions as an Estrogen Receptor (ER) coactivator in breast cancer cells via the citrullination of histone tail arginine residues at ER binding sites. Although an attractive therapeutic target, the mechanisms that regulate PAD2 activity are largely unknown, especially the detailed role of how calcium facilitates enzyme activation. To gain insights into these regulatory processes, we determined the first structures of PAD2 (27 in total), and through calcium-titrations by X-ray crystallography, determined the order of binding and affinity for the six calcium ionsmore » that bind and activate this enzyme. These structures also identified several PAD2 regulatory elements, including a calcium switch that controls proper positioning of the catalytic cysteine residue, and a novel active site shielding mechanism. Additional biochemical and mass-spectrometry-based hydrogen/deuterium exchange studies support these structural findings. The identification of multiple intermediate calcium-bound structures along the PAD2 activation pathway provides critical insights that will aid the development of allosteric inhibitors targeting the PADs.« less