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Article ; Online: Dynamics of CLIMP-63 S-acylation control ER morphology.

Sandoz, Patrick A / Denhardt-Eriksson, Robin A / Abrami, Laurence / Abriata, Luciano A / Spreemann, Gard / Maclachlan, Catherine / Ho, Sylvia / Kunz, Béatrice / Hess, Kathryn / Knott, Graham / S Mesquita, Francisco / Hatzimanikatis, Vassily / van der Goot, F Gisou

Nature communications

2023 Volume 14, Issue 1, Page(s) 264

Abstract: ... elusive. Here, we address the impact of S-acylation, a reversible post-translational lipid modification ... to reach the plasma membrane. However, the majority undergoes S-acylation by ZDHHC6 in the ER ...

Abstract	The complex architecture of the endoplasmic reticulum (ER) comprises distinct dynamic features, many at the nanoscale, that enable the coexistence of the nuclear envelope, regions of dense sheets and a branched tubular network that spans the cytoplasm. A key player in the formation of ER sheets is cytoskeleton-linking membrane protein 63 (CLIMP-63). The mechanisms by which CLIMP-63 coordinates ER structure remain elusive. Here, we address the impact of S-acylation, a reversible post-translational lipid modification, on CLIMP-63 cellular distribution and function. Combining native mass-spectrometry, with kinetic analysis of acylation and deacylation, and data-driven mathematical modelling, we obtain in-depth understanding of the CLIMP-63 life cycle. In the ER, it assembles into trimeric units. These occasionally exit the ER to reach the plasma membrane. However, the majority undergoes S-acylation by ZDHHC6 in the ER where they further assemble into highly stable super-complexes. Using super-resolution microscopy and focused ion beam electron microscopy, we show that CLIMP-63 acylation-deacylation controls the abundance and fenestration of ER sheets. Overall, this study uncovers a dynamic lipid post-translational regulation of ER architecture.
MeSH term(s)	Membrane Proteins/metabolism ; Kinetics ; Endoplasmic Reticulum/metabolism ; Acylation ; Lipids
Chemical Substances	Membrane Proteins ; Lipids
Language	English
Publishing date	2023-01-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-35921-6
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Article ; Online: Different binding modalities of quercetin to inositol-requiring enzyme 1 of S. cerevisiae and human lead to opposite regulation.

Mahdizadeh, S Jalil / Grandén, Johan / Pelizzari-Raymundo, Diana / Guillory, Xavier / Carlesso, Antonio / Chevet, Eric / Eriksson, Leif A

Communications chemistry

2024 Volume 7, Issue 1, Page(s) 6

Abstract: ... in S. cerevisiae (scIre1p), but its impact on human IRE1 (hIRE1) remains controversial due to the absence ...

Abstract	The flavonoid Quercetin (Qe) was identified as an activator of Inositol-requiring enzyme 1 (IRE1) in S. cerevisiae (scIre1p), but its impact on human IRE1 (hIRE1) remains controversial due to the absence of a conserved Qe binding site. We have explored the binding modes and effect of Qe on both scIre1p and hIRE1 dimers using in silico and in vitro approaches. The activation site in scIre1p stably accommodates both Qe and its derivative Quercitrin (Qi), thus enhancing the stability of the RNase pocket. However, the corresponding region in hIRE1 does not bind any of the two molecules. Instead, we show that both Qe and Qi block the RNase activity of hIRE1 in vitro, with sub-micromolar IC
Language	English
Publishing date	2024-01-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2929562-2
ISSN	2399-3669 ; 2399-3669
ISSN (online)	2399-3669
ISSN	2399-3669
DOI	10.1038/s42004-023-01092-0
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Article ; Online: H2O2(s) and H2O2·2H2O(s) crystals compared with ices: DFT functional assessment and D3 analysis.

Arismendi-Arrieta, Daniel J / Sen, Anik / Eriksson, Anders / Broqvist, Peter / Kullgren, Jolla / Hermansson, Kersti

The Journal of chemical physics

2023 Volume 159, Issue 19

Abstract: ... in the literature. Here, we present density functional theory (DFT) calculations for the H2O2(s) and H2O2·2H2O(s ... s) the D3 correction constitutes about 25% of the lattice energy using PBE, much more for RPBE, much ...

Abstract	The H2O and H2O2 molecules resemble each other in a multitude of ways as has been noted in the literature. Here, we present density functional theory (DFT) calculations for the H2O2(s) and H2O2·2H2O(s) crystals and make selected comparisons with ice polymorphs. The performance of a number of dispersion-corrected density functionals-both self-consistent and a posteriori ones-are assessed, and we give special attention to the D3 correction and its effects. The D3 correction to the lattice energies is large: for H2O2(s) the D3 correction constitutes about 25% of the lattice energy using PBE, much more for RPBE, much less for SCAN, and it primarily arises from non-H-bonded interactions out to about 5 Å.The large D3 corrections to the lattice energies are likely a consequence of several effects: correction for missing dispersion interaction, the ability of D3 to capture and correct various other kinds of limitations built into the underlying DFT functionals, and finally some degree of cell-contraction-induced polarization enhancement. We find that the overall best-performing functionals of the twelve examined are optPBEvdW and RPBE-D3. Comparisons with DFT assessments for ices in the literature show that where the same methods have been used, the assessments largely agree.
Language	English
Publishing date	2023-11-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	3113-6
ISSN	1089-7690 ; 0021-9606
ISSN (online)	1089-7690
ISSN	0021-9606
DOI	10.1063/5.0145203
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Article ; Online: Outcome of rare primary malignant bone sarcoma treated with multimodal therapy: Results from the EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.).

Palmerini, Emanuela / Reichardt, Peter / Hall, Kirsten Sundby / Bertulli, Rossella / Bielack, Stefan S / Comandone, Alessandro / Egerer, Gerlinde / Hansmeier, Anna / Kevric, Matthias / Carretta, Elisa / Hansson, Lina / Jebsen, Nina / Eriksson, Mikael / Bruland, Øyvind S / Donati, Davide Maria / Ibrahim, Toni / Smeland, Sigbjørn / Ferrari, Stefano

Cancer

2023 Volume 129, Issue 22, Page(s) 3564–3573

Abstract: ... in the EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S) is presented.: Methods: Inclusion criteria were ...

Abstract	Background: Rare primary malignant bone sarcomas (RPMBS) account for 5%-10% of primary high-grade bone tumors and represent a major treatment challenge. The outcome of patients with RPMBS enrolled in the EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S) is presented. Methods: Inclusion criteria were as follows: age from 41 to 65 years and a diagnosis of high-grade spindle cell, pleomorphic, or vascular RPMBS. The chemotherapy regimen included doxorubicin 60 mg/m Results: In total, 113 patients were evaluable for analysis. The median patient age was 52 years (range, 40-66 years), and 67 patients were men. Eighty-eight tumors were categorized as undifferentiated pleomorphic sarcomas (UPS), 20 were categorized as leiomyosarcomas, three were categorized as fibrosarcomas, and two were categorized as angiosarcomas. Eighty-three of 113 tumors were located in the extremities. Ninety-five of 113 patients presented with no evidence of metastases. After a median follow-up of 6.8 years (interquartile range [IQR], 3.5-9.8 years), the 5-year overall survival rate for patients with localized disease was 68.4% (IQR, 56.9%-77.5%), and it was 71.7% (IQR, 58.1%-81.6%) for patients with UPS and 54.9% (IQR, 29.5%-74.5%) for patients with leiomyosarcoma. Grade III-IV hematologic toxicity was reported in 81% patients; 23% had grade II-III neurotoxicity, and 37.5% had grade I-II nephrotoxicity. Five-year overall survival was significantly better for patients with localized disease, for patients who obtained surgical complete remission, and when the primary tumor was located in the extremities. Conclusions: The survival of patients who had RPMBS in the current series was similar to that of age-matched patients who had high-grade osteosarcoma treated according to the same protocol. An osteosarcoma-like chemotherapy may be proposed in patients who have RPMBS.
MeSH term(s)	Male ; Humans ; Adult ; Middle Aged ; Aged ; Female ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Sarcoma/pathology ; Osteosarcoma/drug therapy ; Combined Modality Therapy ; Bone Neoplasms/pathology ; Doxorubicin ; Ifosfamide ; Leiomyosarcoma/drug therapy
Chemical Substances	Doxorubicin (80168379AG) ; Ifosfamide (UM20QQM95Y)
Language	English
Publishing date	2023-08-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.34964
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Article ; Online: Enhancing the dipolar coupling of a S-T

Abadillo-Uriel, J C / Eriksson, M A / Coppersmith, S N / Friesen, Mark

Nature communications

2019 Volume 10, Issue 1, Page(s) 5641

Abstract: A fundamental challenge for quantum dot spin qubits is to extend the strength and range of qubit interactions while suppressing their coupling to the environment, since both effects have electrical origins. Key tools include the ability to take advantage ...

Abstract	A fundamental challenge for quantum dot spin qubits is to extend the strength and range of qubit interactions while suppressing their coupling to the environment, since both effects have electrical origins. Key tools include the ability to take advantage of physical resources in different regimes, and to access optimal working points, sweet spots, where dephasing is minimized. Here, we explore an important resource for singlet-triplet qubits: a transverse sweet spot (TSS) that enables transitions between qubit states, a strong dipolar coupling, and leading-order protection from electrical fluctuations. Of particular interest is the possibility of transitioning between the TSS and symmetric operating points while remaining continuously protected. This arrangement is ideal for coupling qubits to a microwave cavity, because it combines tunability of the coupling with noise insensitivity. We perform simulations with [Formula: see text]-type electrical noise, demonstrating that two-qubit gates mediated by a resonator can achieve fidelities >99% under realistic conditions.
Language	English
Publishing date	2019-12-10
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-019-13548-w
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Article ; Online: Different binding modalities of quercetin to inositol-requiring enzyme 1 of S. cerevisiae and human lead to opposite regulation

S. Jalil Mahdizadeh / Johan Grandén / Diana Pelizzari-Raymundo / Xavier Guillory / Antonio Carlesso / Eric Chevet / Leif A. Eriksson

Communications Chemistry, Vol 7, Iss 1, Pp 1-

2024 Volume 12

Abstract: ... IRE1) in S. cerevisiae (scIre1p), but its impact on human IRE1 (hIRE1) remains controversial due ...

Abstract	Abstract The flavonoid Quercetin (Qe) was identified as an activator of Inositol-requiring enzyme 1 (IRE1) in S. cerevisiae (scIre1p), but its impact on human IRE1 (hIRE1) remains controversial due to the absence of a conserved Qe binding site. We have explored the binding modes and effect of Qe on both scIre1p and hIRE1 dimers using in silico and in vitro approaches. The activation site in scIre1p stably accommodates both Qe and its derivative Quercitrin (Qi), thus enhancing the stability of the RNase pocket. However, the corresponding region in hIRE1 does not bind any of the two molecules. Instead, we show that both Qe and Qi block the RNase activity of hIRE1 in vitro, with sub-micromolar IC50 values. Our results provide a rationale for why Qe is an activator in scIre1p but a potent inhibitor in hIRE1. The identification of a new allosteric site in hIRE1 opens a promising window for drug development and UPR modulation.
Keywords	Chemistry ; QD1-999
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article ; Online: Association of acylcarnitines with maternal cardiometabolic risk factors is defined by chain length: the S-PRESTO study.

Chen, Li / Goh, Xue Ping / Bendt, Anne K / Tan, Karen Mei-Ling / Leow, Melvin Khee-Shing / Tan, Kok Hian / Chan, Jerry K Y / Chan, Shiao-Yng / Chong, Yap Seng / Gluckman, Peter D / Eriksson, Johan G / Wenk, Markus R / Mir, Sartaj Ahmad

The Journal of clinical endocrinology and metabolism

2024

Abstract: ... PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort study.: Results: Plasma ...

Abstract	Context: Due to the essential role of carnitine as an intermediary in amino acid, carbohydrate and lipid metabolism, a detailed characterization of circulating and urinary carnitine concentrations will aid in elucidating the molecular basis of impaired maternal metabolic flexibility and facilitating timely intervention for expectant mothers. Objective: To investigate the association of maternal plasma and urinary free carnitine and acylcarnitines with cardiometabolic risk factors. Methods: LC-MS/MS-based quantification of free carnitine and acylcarnitines (C2-C18) was performed on 765 plasma and 702 urine samples collected at preconception, 26-28 weeks' pregnancy, and three months postpartum in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort study. Results: Plasma concentrations of free carnitine and acylcarnitines decreased coupled with increased renal clearance in pregnancy compared to preconception and postpartum. Renal clearance of carnitine increased with an increase in pre-pregnancy body mass index (ppBMI) and gestational weight gain. Plasma short-chain acylcarnitines were positively associated with ppBMI, irrespective of the physiological state, while medium- and long-chain acylcarnitines were negatively associated with ppBMI at preconception and postpartum but showed a positive association in pregnancy. Similarly, plasma short-chain acylcarnitines were positively associated with HOMA-IR whereas medium- and long-chain acylcarnitines were negatively associated with HOMA-IR at preconception and in pregnancy. Mothers who developed gestational diabetes mellitus during pregnancy had ∼10% higher plasma propionylcarnitine concentration and ∼18% higher urine tiglylcarnitine concentration compared to mothers with normal glucose metabolism at preconception. Conclusions: This study provides the metabolic and physiological basis of maternal carnitine homeostasis, which can be used in assessment of maternal cardiometabolic health at preconception to improve pregnancy outcomes.
Language	English
Publishing date	2024-04-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgae255
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Article: Intravenous S-ketamine's analgesic efficacy in third molar surgery. A randomized placebo-controlled double-blind clinical trial.

Eriksson, Lars B / Gordh, Torsten / Karlsten, Rolf / LoMartire, Riccardo / Thor, Andreas / Tegelberg, Åke

British journal of pain

2023 Volume 18, Issue 2, Page(s) 197–208

Abstract: ... In day-case, surgery; however, opioids should be avoided. Thus, the anaesthetic agent S-ketamine ... The patients were randomized into three groups where two doses of S-ketamine were compared (high: 0.25 mg/kg or ... h postoperatively, showed no significant difference between the placebo and high-dose S-ketamine ...

Abstract	Background: In most cases, a combination of paracetamol and ibuprofen are the optimal treatment for postoperative pain in third molar surgery. If stronger analgesia is required, opioids are traditionally administered. In day-case, surgery; however, opioids should be avoided. Thus, the anaesthetic agent S-ketamine in analgesic doses might be preferred. Methods: The study was designed as a randomized placebo-controlled double-blind clinical trial. The study enrolled healthy subjects according to the American Society of Anaesthesiologists classification; I or II (ASA), aged 18 to 44 years, with a body weight between 50 and 100 kg. The patients were randomized into three groups where two doses of S-ketamine were compared (high: 0.25 mg/kg or low: 0.125 mg/kg) with placebo (saline). Results: A primary outcome of the study was that VAS at 4 h postoperatively, showed no significant difference between the placebo and high-dose S-ketamine group or in the low-dose group. We found a significant difference between the groups for the first 24 h, with a lower VAS-score in the high-dose S-ketamine group. The time to when 50% had taken their first rescue medication was 12 min later in the high-dose ketamine group. Conclusions: Pre-emptive S-ketamine 0.25 mg/kg gave a global significant reduction of pain by VAS during the first 24 h postoperatively. The time from end of surgery to first rescue medication were longer in the high-dose ketamine group compared to both low-dose ketamine and placebo groups.
Language	English
Publishing date	2023-12-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2670872-3
ISSN	2049-4645 ; 2049-4637
ISSN (online)	2049-4645
ISSN	2049-4637
DOI	10.1177/20494637231222327
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Article ; Online: Development of a short-form Swedish version of the Montreal Cognitive Assessment (s-MoCA-SWE): protocol for a cross-sectional study.

Abzhandadze, Tamar / Lundström, Erik / Buvarp, Dongni / Eriksson, Marie / Quinn, Terence J / Sunnerhagen, Katharina S

BMJ open

2021 Volume 11, Issue 5, Page(s) e049035

Abstract: ... of patients with stroke.The aim is to develop a short-form Swedish version of the MoCA (s-MoCA-SWE ... a subgroup of MoCA items that have the potential to form the s-MoCA-SWE; (2) to determine the optimal cut-off ... value of s-MoCA-SWE for predicting cognitive impairment and (3) and to compare the psychometric ...

Abstract	Introduction: Short forms of the Montreal Cognitive Assessment (MoCA) have allowed quick cognitive screening. However, none of the available short forms has been created or validated in a Swedish sample of patients with stroke.The aim is to develop a short-form Swedish version of the MoCA (s-MoCA-SWE) in a sample of patients with acute and subacute stroke. The specific objectives are: (1) to identify a subgroup of MoCA items that have the potential to form the s-MoCA-SWE; (2) to determine the optimal cut-off value of s-MoCA-SWE for predicting cognitive impairment and (3) and to compare the psychometric properties of s-MoCA-SWE with those of previously developed MoCA short forms. Methods and analysis: This is a statistical analysis protocol for a cross-sectional study. The study sample will comprise patients from Väststroke, a local stroke registry from Gothenburg, Sweden and Efficacy oF Fluoxetine-a randomisEd Controlled Trial in Stroke (EFFECTS), a randomised controlled trial in Sweden. The s-MoCA-SWE will be developed by using exploratory factor analysis and the boosted regression tree algorithm. The cut-off value of s-MoCA-SWE for impaired cognition will be determined based on binary logistic regression analysis. The psychometric properties of s-MoCA-SWE will be compared with those of other MoCA short forms by using cross-tabulation and area under the receiving operating characteristic curve analyses. Ethics and dissemination: The Väststroke study has received ethical approval from the Regional Ethical Review Board in Gothenburg (346-16) and the Swedish Ethical Review Authority (amendment 2019-04299). The handling of data generated within the framework of quality registers does not require written informed consent from patients. The EFFECTS study has received ethical approval from the Stockholm Ethics Committee (2013/1265-31/2 on 30 September 2013). All participants provided written consent. Results will be published in an international, peer-reviewed journal, presented at conferences and communicated to clinical practitioners in local meetings and seminars.
MeSH term(s)	Cognitive Dysfunction ; Cross-Sectional Studies ; Humans ; Mental Status and Dementia Tests ; Neuropsychological Tests ; Randomized Controlled Trials as Topic ; Stroke ; Sweden
Language	English
Publishing date	2021-05-03
Publishing country	England
Document type	Clinical Trial Protocol ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2021-049035
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Book ; Online: Fish and fish-based products in Timor-Leste’s School Meal Program

Bonis-Profumo, Gianna / Hunnam, Kimberly / Duarte, Agustinha / Pinto, Abelita / Simões, Noviana / Martins, Joaquim / Monteira, Melita / Marques, Epifania / Barreto, Celestino / de Sousa, Alda / Soares, Zulmira / Hayashi, Tomomi / Saha, Saikat / Klumpyan, Katherine / Soriano, Anastacio / Pant, Jharendu / Eriksson, Hampus

Understanding existing use, challenges, opportunities and research needs

2023

Abstract: Workshop with government agencies and organisations involved in Timor-Leste’s School Meal Program ...

Abstract	Workshop with government agencies and organisations involved in Timor-Leste’s School Meal Program (PME) shared experiences about using fish in the program and identified focal areas for research. There is wide recognition for the role of aquatic foods and that greater inclusion of aquatic foods in the program requires cooperation and collaboration between partners. Not enough fish is produced in Timor-Leste for domestic supply to meet demand and PME goals. There is a need to build school level capacity for planning, procurement and meal preparation with aquatic foods.
Keywords	nutrition ; fish products ; school meals ; fish
Language	English
Publishing date	2023-12-18T21:49:33Z
Publisher	WorldFish
Publishing country	fr
Document type	Book ; Online
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