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  1. Article: A cross-organizational Lean deployment in an Italian regional healthcare system.

    Rosa, Angelo / Marolla, Giuliano / McDermott, Olivia

    International journal of health care quality assurance

    2023  Volume ahead-of-print, Issue ahead-of-print

    Abstract: Purpose: This study explores how Lean was deployed in several hospitals in the Apulia region in Italy over 3.5 years.: Design/methodology/approach: An exploratory qualitative design was drawn up based on semi-structured interviews.: Findings: The ... ...

    Abstract Purpose: This study explores how Lean was deployed in several hospitals in the Apulia region in Italy over 3.5 years.
    Design/methodology/approach: An exploratory qualitative design was drawn up based on semi-structured interviews.
    Findings: The drivers of Lean in hospitals were to increase patient satisfaction and improve workplace well-being by eliminating non-value-add waste. The participants highlighted three key elements of the pivotal implementation stages of Lean: introduction, spontaneous and informal dissemination and strategic level implementation and highlighted critical success and failure factors that emerged for each of these stages. During the introduction, training and coaching from an external consultant were among the most impactful factors in the success of pilot projects, while time constraints and the adoption of process analysis tools were the main barriers to implementation. The experiences of the Lean teams strongly influence the process of spontaneous dissemination aided by the celebration of project results and the commitment of the departmental hospital heads.
    Practical implications: Lean culture can spread to allow many projects be conducted spontaneously, but the Lean paradigm can struggle to be adopted strategically. Lean in healthcare can fail because of the lack of alignment of Lean with leadership in healthcare and with their strategic vision, a lack of employees' project management skills and crucially the absence of a Lean steering committee.
    Originality/value: The absence of managerial expertise and a will to support Lean implementation do not allow for systemic adoption of Lean. This is one of the first and largest long-term case studies on a Lean cross-regional multi-hospital application in healthcare.
    MeSH term(s) Humans ; Hospitals ; Leadership ; Italy ; Patient Satisfaction
    Language English
    Publishing date 2023-10-24
    Publishing country England
    Document type Case Reports
    ZDB-ID 645125-1
    ISSN 0952-6862 ; 1366-0756
    ISSN 0952-6862 ; 1366-0756
    DOI 10.1108/IJHCQA-06-2023-0045
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2499: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Advanced heart failure and heart transplantation in adult congenital heart disease in the current era.

    de la Rosa, Angelo L / Singer-Englar, Tahli / Tompkins, Rose O / Patel, Jignesh K / Kobashigawa, Jon A / Kittleson, Michelle M

    Clinical transplantation

    2021  Volume 35, Issue 11, Page(s) e14451

    Abstract: Background: Adults with congenital heart disease (ACHD) may undergo heart transplantation (HTx) despite increased risk of poor short-term outcomes due to factors including surgical complexity and antibody sensitization. We assessed the clinical ... ...

    Abstract Background: Adults with congenital heart disease (ACHD) may undergo heart transplantation (HTx) despite increased risk of poor short-term outcomes due to factors including surgical complexity and antibody sensitization. We assessed the clinical characteristics and outcomes of patients with ACHD in the current era referred for HTx at a single high-volume transplant center.
    Methods: From 2010 to 2020, 37 ACHD patients were evaluated for HTx. ACHD HTx recipients were compared to non-ACHD HTx recipients matched for age, sex, listing status, and prior cardiac surgery.
    Results: Of the 37 patients with ACHD, eight (21.6%) were declined for HTx. Of 29 ACHD patients listed, 19 (65.5%) underwent HTx. Compared with non-ACHD HTx controls, the ACHD HTx recipients had more treated cellular (21.1% vs. 15.8%, P = .010) and antibody-mediated (15.8% vs. 10.5%, P = .033) rejection. There was no difference in hospital readmission or allograft vasculopathy at 1 year. There was a nonsignificant higher 1-year mortality in ACHD HTx recipients (21.1% vs. 7.9%, P = .21).
    Conclusion: At a high-volume transplant center, ACHD patients undergoing HTx appear to have a marginally higher risk of rejection, but no significant increase in 1-year mortality. With careful selection and management, HTx for patients with ACHD may be feasible in the current era.
    MeSH term(s) Adult ; Heart Defects, Congenital/surgery ; Heart Failure/surgery ; Heart Transplantation ; Humans ; Survival Rate
    Language English
    Publishing date 2021-09-12
    Publishing country Denmark
    Document type Journal Article
    ZDB-ID 639001-8
    ISSN 1399-0012 ; 0902-0063
    ISSN (online) 1399-0012
    ISSN 0902-0063
    DOI 10.1111/ctr.14451
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2204: Show issues Location:
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  3. Article: Patterns of functional diversity of native and non‐native fish species in a neotropical floodplain

    Angulo‐Valencia, Mirtha A. / Dias, Rosa M. / Alves, Diego C. / Winemiller, Kirk O. / Agostinho, Angelo A.

    Freshwater biology. 2022 Aug., v. 67, no. 8

    2022  

    Abstract: Human activities affecting freshwater ecosystems, such as regulation of rivers by dams and introduction of non‐native species, are recognised as major threats to freshwater biodiversity, with fish communities strongly impacted. We evaluated patterns of ... ...

    Abstract Human activities affecting freshwater ecosystems, such as regulation of rivers by dams and introduction of non‐native species, are recognised as major threats to freshwater biodiversity, with fish communities strongly impacted. We evaluated patterns of functional diversity of native and non‐native species in local fish assemblages in the upper Paraná River floodplain over a 33‐year period (1986–2019) in three rivers with different degrees of alteration by dams (highly altered, moderately altered, and little altered). We also examined the effect of non‐native species on functional diversity of native species and investigated the responses of functional traits of native and non‐native fishes in regions with different histories of flow alteration. We measured 13 functional traits associated with five niche dimensions: feeding, habitat use, metabolism, life history, and defence. Functional diversity was evaluated from functional richness, functional redundancy, and Rao's quadratic entropy. The effect of non‐native species on functional diversity indices of native species was evaluated using a simple linear regression between each index and the level of dominance by non‐native species. To evaluate changes in functional traits of native and non‐native species over time and among rivers, we performed an RLQ analysis. Functional richness and Rao's quadratic entropy of native species decreased over time, while functional redundance increased especially in the most altered river. The level of dominance by non‐native species was negatively associated with functional richness and Rao's quadratic entropy of native species. Native species that are migratory with high fecundity, single spawning events and large body size were most common during the first 2 decades and within the least altered river. Non‐native species with parental care, multiple spawning, relatively large eggs, and brood defence tended to have greater prevalence during the last 2 decades and within the moderately altered region. Comparison of temporal trends in the functional diversity and characteristics of native and non‐native fishes within regions of the upper Paraná River floodplain having different levels of environmental alteration suggests that non‐native species and alteration by dams interact to adversely impact the functional diversity of native fishes, with especially strong effects on migratory fishes with a periodic life history strategy.
    Keywords Neotropics ; body size ; entropy ; fecundity ; fish ; floodplains ; freshwater ; functional diversity ; habitat preferences ; humans ; indigenous species ; introduced species ; life history ; limnology ; metabolism ; migratory behavior ; regression analysis ; rivers
    Language English
    Dates of publication 2022-08
    Size p. 1301-1315.
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note JOURNAL ARTICLE
    ZDB-ID 121180-8
    ISSN 0046-5070
    ISSN 0046-5070
    DOI 10.1111/fwb.13918
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  4. Article ; Online: White matter tauopathy: Transient functional loss and novel myelin remodeling.

    Jackson, Joshua / Bianco, Gabby / Rosa, Angelo O / Cowan, Katrina / Bond, Peter / Anichtchik, Oleg / Fern, Robert

    Glia

    2018  Volume 66, Issue 4, Page(s) 813–827

    Abstract: Early white matter (WM) changes are common in dementia and may contribute to functional decline. We here examine this phenomenon in an induced dementia model for the first time. We report a novel and selective form of myelin injury as the first ... ...

    Abstract Early white matter (WM) changes are common in dementia and may contribute to functional decline. We here examine this phenomenon in an induced dementia model for the first time. We report a novel and selective form of myelin injury as the first manifestation of tauopathy in the adult central nervous system. Myelin pathology rapidly followed the induction of a P301 tau mutation associated with fronto-temporal dementia in humans (rTG4510 line). Damage involved focal disruption of the ad-axonal myelin lamella and internal oligodendrocyte tongue process, followed by myelin remodeling with features of re-myelination that included myelin thinning and internodal shortening. The evolution of the re-myelinated phenotype was complete in the molecular layer of the dentate gyrus after 1 month and in the optic nerve (ON) after 9 months of transgene induction and proceeded in the absence of actual demyelination, reactive glial changes or inflammatory response. The initial rapid myelin pathology was associated with loss of WM function and performance decline in a novel recognition test and both these effects largely reversed during the myelin re-modeling phase. The initial phase of myelin injury was accompanied by disruption of the vesicle population present in the axoplasm of hippocampal and ON axons. Axoplasmic vesicle release is significant for the regulation of myelin plasticity and disruption of this pathway may underlie the myelin damage and remodeling evoked by tauopathy. WM dysfunction early in tauopathy will disorder neural circuits, the current findings suggest this event may make a significant contribution to early clinical deficit in dementia.
    MeSH term(s) Animals ; Astrocytes/pathology ; Astrocytes/physiology ; Axons/pathology ; Axons/physiology ; Cytoplasmic Vesicles/metabolism ; Cytoplasmic Vesicles/pathology ; Disease Progression ; Hippocampus/pathology ; Hippocampus/physiopathology ; Humans ; Male ; Memory Disorders/pathology ; Memory Disorders/physiopathology ; Mice, Inbred C57BL ; Mice, Transgenic ; Myelin Sheath/pathology ; Myelin Sheath/physiology ; Optic Nerve/pathology ; Optic Nerve/physiopathology ; Recognition (Psychology)/physiology ; Tauopathies/pathology ; Tauopathies/physiopathology ; Tauopathies/psychology ; White Matter/pathology ; White Matter/physiopathology ; tau Proteins/genetics ; tau Proteins/metabolism
    Chemical Substances MAPT protein, human ; tau Proteins
    Language English
    Publishing date 2018-01-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639414-0
    ISSN 1098-1136 ; 0894-1491
    ISSN (online) 1098-1136
    ISSN 0894-1491
    DOI 10.1002/glia.23286
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    Zs.A 2345: Show issues Location:
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  5. Article ; Online: Mechanical regulation of native and the recombinant calcium channel.

    Rosa, Angelo O / Yamaguchi, Naohiro / Morad, Martin

    Cell calcium

    2013  Volume 53, Issue 4, Page(s) 264–274

    Abstract: L-type calcium channels are modulated by a host of mechanisms that include voltage, calcium ions (Ca(2+) dependent inactivation and facilitation), cytosolic proteins (CAM, CAMKII, PKA, PKC, etc.), and oxygen radicals. Here we describe yet another Ca(2+) ... ...

    Abstract L-type calcium channels are modulated by a host of mechanisms that include voltage, calcium ions (Ca(2+) dependent inactivation and facilitation), cytosolic proteins (CAM, CAMKII, PKA, PKC, etc.), and oxygen radicals. Here we describe yet another Ca(2+) channel regulatory mechanism that is induced by pressure-flow (PF) forces of ∼25dyn/cm(2) producing 35-60% inhibition of channel current. Only brief periods (300ms) of such PF pulses were required to suppress reversibly the current. Recombinant Ca(2+) channels (α1c77/β2a/α2δ and α1c77/β1/α2δ), expressed in HEK293 cells, were similarly suppressed by PF pulses. To examine whether Ca(2+) released by PF pulses triggered from different sub-cellular compartments (SR, ER, mitochondria) underlies the inhibitory effect of PF on the channel current, pharmacological agents and ionic substitutions were employed to probe this possibility. No significant difference in effectiveness of PF pulses to suppress ICa or IBa (used to inhibit CICR) was found between control cells and those exposed to U73122 and 2-APB (PLC and IP3R pathway modulators), thapsigargin and BAPTA (SERCA2a modulator), dinitrophenol, FCCP and Ru360 (mitochondrial inhibitors), l-NAME (NOS inhibitor signaling), cAMP and Pertussis toxin (Gi protein modulator). We concluded that the rapid and reversible modulation of the Ca(2+) channel by PF pulses is independent of intracellular release of Ca(2+) and Ca(2+) dependent inactivation of the channel and may represent direct mechanical regulatory effect on the channel protein in addition to previously reported Ca(2+)-release or entry dependent mechanism.
    MeSH term(s) Calcium/metabolism ; Calcium Channels/metabolism ; Cells, Cultured ; HEK293 Cells ; Humans ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/metabolism ; Recombinant Proteins/metabolism
    Chemical Substances Calcium Channels ; Recombinant Proteins ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2013-01-26
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 757687-0
    ISSN 1532-1991 ; 0143-4160
    ISSN (online) 1532-1991
    ISSN 0143-4160
    DOI 10.1016/j.ceca.2012.12.007
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1596: Show issues Location:
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  6. Article: Intracellular- and extracellular-derived Ca(2+) influence phospholipase A(2)-mediated fatty acid release from brain phospholipids.

    Rosa, Angelo O / Rapoport, Stanley I

    Biochimica et biophysica acta

    2009  Volume 1791, Issue 8, Page(s) 697–705

    Abstract: Docosahexaenoic acid (DHA) and arachidonic acid (AA) are found in high concentrations in brain cell membranes and are important for brain function and structure. Studies suggest that AA and DHA are hydrolyzed selectively from the sn-2 position of ... ...

    Abstract Docosahexaenoic acid (DHA) and arachidonic acid (AA) are found in high concentrations in brain cell membranes and are important for brain function and structure. Studies suggest that AA and DHA are hydrolyzed selectively from the sn-2 position of synaptic membrane phospholipids by Ca(2+)-dependent cytosolic phospholipase A(2) (cPLA(2)) and Ca(2+)-independent phospholipase A(2) (iPLA(2)), respectively, resulting in increased levels of the unesterified fatty acids and lysophospholipids. Cell studies also suggest that AA and DHA release depend on increased concentrations of Ca(2+), even though iPLA(2) has been thought to be Ca(2+)-independent. The source of Ca(2+) for activation of cPLA(2) is largely extracellular, whereas Ca(2+) released from the endoplasmic reticulum can activate iPLA(2) by a number of mechanisms. This review focuses on the role of Ca(2+) in modulating cPLA(2) and iPLA(2) activities in different conditions. Furthermore, a model is suggested in which neurotransmitters regulate the activity of these enzymes and thus the balanced and localized release of AA and DHA from phospholipid in the brain, depending on the primary source of the Ca(2+) signal.
    MeSH term(s) Animals ; Brain/enzymology ; Brain/metabolism ; Brain/pathology ; Calcium/metabolism ; Extracellular Space/metabolism ; Fatty Acids/metabolism ; Humans ; Intracellular Space/metabolism ; Phospholipases A2/metabolism ; Phospholipids/metabolism
    Chemical Substances Fatty Acids ; Phospholipids ; Phospholipases A2 (EC 3.1.1.4) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2009-03-25
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Review
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbalip.2009.03.009
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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.247: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: Metabolic Systems Analysis of Shock-Induced Endotheliopathy (SHINE) in Trauma: A New Research Paradigm.

    Henriksen, Hanne H / McGarrity, Sarah / SigurÐardóttir, Rósa S / Nemkov, Travis / D'Alessandro, Angelo / Palsson, Bernhard O / Stensballe, Jakob / Wade, Charles E / Rolfsson, Óttar / Johansson, Pär I

    Annals of surgery

    2019  Volume 272, Issue 6, Page(s) 1140–1148

    Abstract: Objective: Investigate the endothelial cell phenotype (s) that causes Shock-Induced Endotheliopathy in trauma.: Background: We have studied more than 2750 trauma patients and identified that patients with high circulating syndecan-1 (endothelial ... ...

    Abstract Objective: Investigate the endothelial cell phenotype (s) that causes Shock-Induced Endotheliopathy in trauma.
    Background: We have studied more than 2750 trauma patients and identified that patients with high circulating syndecan-1 (endothelial glycocalyx damage marker) in plasma have an increased mortality rate compared with patients with lower levels. Notably, we found that patients suffering from the same trauma severity could develop significantly different degrees of endothelial dysfunction as measured by syndecan-1.
    Methods: Prospective observational study of 20 trauma patients admitted to a Level 1 Trauma Centre and 20 healthy controls. Admission plasma syndecan-1 level and mass spectrometry were measured and analyzed by computational network analysis of our genome-scale metabolic model of the microvascular endothelial cell function.
    Results: Trauma patients had a significantly different endothelial metabolic profile compared with controls. Among the patients, 4 phenotypes were identified. Three phenotypes were independent of syndecan-1 levels. We developed genome-scale metabolic models representative of the observed phenotypes. Within these phenotypes, we observed differences in the cell fluxes from glucose and palmitate to produce Acetyl-CoA, and secretion of heparan sulfate proteoglycan (component of syndecan-1).
    Conclusions: We confirm that trauma patients have a significantly different metabolic profile compared with controls. A minimum of 4 shock-induced endotheliopathy phenotypes were identified, which were independent of syndecan-1level (except 1 phenotype) verifying that the endothelial response to trauma is heterogeneous and most likely driven by a genetic component. Moreover, we introduced a new research tool in trauma by using metabolic systems biology, laying the foundation for personalized medicine.
    MeSH term(s) Adult ; Biomedical Research ; Endothelial Cells ; Endothelium, Vascular ; Female ; Humans ; Male ; Middle Aged ; Phenotype ; Prospective Studies ; Shock/blood ; Shock/complications ; Shock/metabolism ; Syndecan-1/blood ; Vascular Diseases/blood ; Vascular Diseases/etiology ; Vascular Diseases/metabolism ; Wounds and Injuries/blood ; Wounds and Injuries/complications
    Chemical Substances SDC1 protein, human ; Syndecan-1
    Language English
    Publishing date 2019-07-03
    Publishing country United States
    Document type Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 340-2
    ISSN 1528-1140 ; 0003-4932
    ISSN (online) 1528-1140
    ISSN 0003-4932
    DOI 10.1097/SLA.0000000000003307
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    In stock of ZB MED Cologne/Königswinter

    Uk I Zs.35/1: Show issues Location:
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  8. Article: Mechanical regulation of native and the recombinant calcium channel

    Rosa, Angelo O / Yamaguchi, Naohiro / Morad, Martin

    Cell calcium. 2013 Apr., v. 53, no. 4

    2013  

    Abstract: L-type calcium channels are modulated by a host of mechanisms that include voltage, calcium ions (Ca2+ dependent inactivation and facilitation), cytosolic proteins (CAM, CAMKII, PKA, PKC, etc.), and oxygen radicals. Here we describe yet another Ca2+ ... ...

    Abstract L-type calcium channels are modulated by a host of mechanisms that include voltage, calcium ions (Ca2+ dependent inactivation and facilitation), cytosolic proteins (CAM, CAMKII, PKA, PKC, etc.), and oxygen radicals. Here we describe yet another Ca2+ channel regulatory mechanism that is induced by pressure-flow (PF) forces of ∼25dyn/cm2 producing 35–60% inhibition of channel current. Only brief periods (300ms) of such PF pulses were required to suppress reversibly the current. Recombinant Ca2+ channels (α1c77/β2a/α2δ and α1c77/β1/α2δ), expressed in HEK293 cells, were similarly suppressed by PF pulses. To examine whether Ca2+ released by PF pulses triggered from different sub-cellular compartments (SR, ER, mitochondria) underlies the inhibitory effect of PF on the channel current, pharmacological agents and ionic substitutions were employed to probe this possibility. No significant difference in effectiveness of PF pulses to suppress ICa or IBa (used to inhibit CICR) was found between control cells and those exposed to U73122 and 2-APB (PLC and IP3R pathway modulators), thapsigargin and BAPTA (SERCA2a modulator), dinitrophenol, FCCP and Ru360 (mitochondrial inhibitors), l-NAME (NOS inhibitor signaling), cAMP and Pertussis toxin (Gi protein modulator). We concluded that the rapid and reversible modulation of the Ca2+ channel by PF pulses is independent of intracellular release of Ca2+ and Ca2+ dependent inactivation of the channel and may represent direct mechanical regulatory effect on the channel protein in addition to previously reported Ca2+-release or entry dependent mechanism.
    Keywords cAMP-dependent protein kinase ; calcium ; calcium channels ; ions ; mitochondria ; pertussis toxin ; protein kinase C ; reactive oxygen species
    Language English
    Dates of publication 2013-04
    Size p. 264-274.
    Publishing place Elsevier India Pvt Ltd.
    Document type Article
    ZDB-ID 757687-0
    ISSN 1532-1991 ; 0143-4160
    ISSN (online) 1532-1991
    ISSN 0143-4160
    DOI 10.1016/j.ceca.2012.12.007
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1596: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  9. Article ; Online: Hypoxic regulation of cardiac Ca2+ channel: possible role of haem oxygenase.

    Rosa, Angelo O / Movafagh, Shahrzad / Cleemann, Lars / Morad, Martin

    The Journal of physiology

    2012  Volume 590, Issue 17, Page(s) 4223–4237

    Abstract: ... affecting the channel. To address this question we measured the early effects of hypoxia (5-60 s, P(O(2 ...

    Abstract Acute and chronic hypoxias are common cardiac diseases that lead often to arrhythmia and impaired contractility. At the cellular level it is unclear whether the suppression of cardiac Ca(2+) channels (Ca(V)1.2) results directly from oxygen deprivation on the channel protein or is mediated by intermediary proteins affecting the channel. To address this question we measured the early effects of hypoxia (5-60 s, P(O(2)) < 5 mmHg) on Ca(2+) current (I(Ca)) and tested the involvement of protein kinase A (PKA) phosphorylation, Ca(2+)/calmodulin-mediated signalling and the haem oxygenase (HO) pathway in the hypoxic regulation of Ca(V)1.2 in rat and cat ventricular myocytes and HEK-293 cells. Hypoxic suppression of ICa) and Ca(2+) transients was significant within 5 s and intensified in the following 50 s, and was reversible. Phosphorylation by cAMP or the phosphatase inhibitor okadaic acid desensitized I(Ca) to hypoxia, while PKA inhibition by H-89 restored the sensitivity of I(Ca) to hypoxia. This phosphorylation effect was specific to Ca(2+), but not Ba(2+) or Na(+), permeating through the channel. CaMKII inhibitory peptide and Bay K8644 reversed the phosphorylation-induced desensitization to hypoxia. Mutation of CAM/CaMKII-binding motifs of the α(1c) subunit of Ca(V)1.2 fully desensitized the Ca(2+) channel to hypoxia. Rapid application of HO inhibitors (zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP)) suppressed the channel in a manner similar to acute hypoxia such that: (1) I(Ca) and I(Ba) were suppressed within 5 s of ZnPP application; (2) PKA activation and CaMKII inhibitors desensitized I(Ca), but not I(Ba), to ZnPP; and (3) hypoxia failed to further suppress I(Ca) and I(Ba) in ZnPP-treated myocytes. We propose that the binding of HO to the CaM/CaMKII-specific motifs on Ca(2+) channel may mediate the rapid response of the channel to hypoxia.
    MeSH term(s) Amino Acid Sequence ; Animals ; Binding Sites ; Calcium Channels, L-Type/chemistry ; Calcium Channels, L-Type/genetics ; Calcium Channels, L-Type/metabolism ; Calcium Signaling ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/chemistry ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism ; Calmodulin/metabolism ; Cats ; Cell Hypoxia ; Cyclic AMP-Dependent Protein Kinases/metabolism ; HEK293 Cells ; Heme Oxygenase (Decyclizing)/antagonists & inhibitors ; Heme Oxygenase (Decyclizing)/metabolism ; Humans ; Hypoxia/metabolism ; Molecular Sequence Data ; Myocardium/metabolism ; Myocytes, Cardiac/metabolism ; Phosphorylation ; Rats
    Chemical Substances Calcium Channels, L-Type ; Calmodulin ; Heme Oxygenase (Decyclizing) (EC 1.14.14.18) ; Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11) ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 (EC 2.7.11.17)
    Language English
    Publishing date 2012-07-02
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/jphysiol.2012.236570
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Search for Dark-Matter-Nucleon Interactions via Migdal Effect with DarkSide-50.

    Agnes, P / Albuquerque, I F M / Alexander, T / Alton, A K / Ave, M / Back, H O / Batignani, G / Biery, K / Bocci, V / Bonivento, W M / Bottino, B / Bussino, S / Cadeddu, M / Cadoni, M / Calaprice, F / Caminata, A / Campos, M D / Canci, N / Caravati, M /
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    Physical review letters

    2023  Volume 130, Issue 10, Page(s) 101001

    Abstract: Dark matter elastic scattering off nuclei can result in the excitation and ionization of the recoiling atom through the so-called Migdal effect. The energy deposition from the ionization electron adds to the energy deposited by the recoiling nuclear ... ...

    Abstract Dark matter elastic scattering off nuclei can result in the excitation and ionization of the recoiling atom through the so-called Migdal effect. The energy deposition from the ionization electron adds to the energy deposited by the recoiling nuclear system and allows for the detection of interactions of sub-GeV/c^{2} mass dark matter. We present new constraints for sub-GeV/c^{2} dark matter using the dual-phase liquid argon time projection chamber of the DarkSide-50 experiment with an exposure of (12 306±184)  kg d. The analysis is based on the ionization signal alone and significantly enhances the sensitivity of DarkSide-50, enabling sensitivity to dark matter with masses down to 40  MeV/c^{2}. Furthermore, it sets the most stringent upper limit on the spin independent dark matter nucleon cross section for masses below 3.6  GeV/c^{2}.
    Language English
    Publishing date 2023-03-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208853-8
    ISSN 1079-7114 ; 0031-9007
    ISSN (online) 1079-7114
    ISSN 0031-9007
    DOI 10.1103/PhysRevLett.130.101001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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