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SLC10A7 regulates O-GalNAc glycosylation and Ca(2+) homeostasis in the secretory pathway: insights into SLC10A7-CDG.
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317444.pdf (Publisher’s version ) (Open Access)Glycans are known to be fundamental for many cellular and physiological functions. Congenital disorders of glycosylation (CDG) currently encompassing over 160 subtypes, are characterized by glycan synthesis and/or processing defects. Despite the increasing number of CDG patients, therapeutic options remain very limited as our knowledge on glycan synthesis is fragmented. The emergence of CDG resulting from defects in ER/ Golgi homeostasis makes this even more difficult. SLC10A7 belongs to the SLC10 protein family, known as bile acid and steroid transport family, exhibiting a unique structure. It shows a ubiquitous expression and is linked to negative calcium regulation in cells. The mechanisms by which SLC10A7 deficiency leads to Golgi glycosylation abnormalities are unknown. The present study identifies major O-glycosylation defects in both SLC10A7 KO HAP1 cells and SLC10A7-CDG patient fibroblasts and reveals an increased ER and Golgi calcium contents. We also show that the abundance of COSMC and C1GALT1 is altered in SLC10A7-CDG patient cells, as well as the subcellular Golgi localization of the Ca(2+)-binding Cab45 protein. Finally, we demonstrate that supraphysiological manganese supplementation suppresses the deficient electrophoretic mobility of TGN46 by an aberrant transfer of GalNAc residues, and reveal COSMC Mn(2+) sensitivity. These findings provide novel insights into the mechanisms of Golgi glycosylation defects in SLC10A7-deficient cells. They show that SLC10A7 is a key Golgi transmembrane protein maintaining the tight regulation of Ca(2+) homeostasis in the ER and Golgi compartments, both essential for glycosylation
Assessment of fully quantitative and simplified methods for analysis of [(68)Ga]Ga-FAPI-46 uptake in patients with pancreatobiliary cancer using LAFOV PET/CT.
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316833.pdf (Publisher’s version ) (Open Access)PURPOSE: The aim of this study was to validate simplified methods for quantifying [(68)Ga]Ga-FAPI-46 uptake against full pharmacokinetic modeling. METHODS: Ten patients with pancreatobiliary cancer underwent a 90-min dynamic PET/CT scan using a long axial field of view system. Arterial blood samples were used to establish calibrated plasma-input function from both continuous arterial sampling and image-derived input function (IDIF). Lesional [(68)Ga]Ga-FAPI-46 kinetics were described using conventional non-linear plasma-input tissue-compartment models. Logan plots using 30-90 min and 30-60 min post-injection (p.i), image-based target-to-whole blood ratio (TBR), mean standardized uptake values (SUVmean) normalized to body weight, lean body mass, and body surface area, at 20-30 min, 60-70 min and 80-90 min p.i were assessed. RESULTS: One patient was excluded due to discontinued scan acquisition and missing arterial sampling. Thirteen tumoral lesions and 11 non-tumoral lesions were included. A reversible 2-tissue-compartment model showed most preferrable fits for all types of [(68)Ga]Ga-FAPI-46 positive lesions. The distribution volume (V(T)) results obtained using arterial sampling plasma-input function and those using plasma-IDIF (V(T_plasma_IDIF)) showed an excellent correlation (Spearman rank correlation coefficient (r(s)) = 0.949). Logan V(T) using both time intervals were highly correlated with V(T_plasma_IDIF) (r(s) ≥ 0.938). The correlation values with V(T_plasma_IDIF) for image-based TBR and SUVmean parameters were higher at 80-90 min (r(s) ≥ 0.839) and at 60-70 min (r(s) ≥ 0.835) p.i than at 20-30 min p.i (r(s) ≤ 0.774). CONCLUSION: Image-based TBR and SUVmean at 60-70 min p.i are suitable for quantifying [(68)Ga]Ga-FAPI-46 uptake. TRIAL REGISTRATION: EudraCT, EudraCT 2022-001867-29. Registered 02 November 2022
Internationale Bildungskooperation im Bereich Deutsch als Fremdsprache. State of the Art & Perspektiven
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Searches for signatures of ultralight axion dark matter in polarimetry data of the European Pulsar Timing Array
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317961.pdf (Publisher’s version ) (Open Access
De rechtspositie van de bank als noodfinancier
No full textItem does not contain fulltext06 februari 2025Ministerie van Justitie en VeiligheidInvited lectur
Short Paper: Effects of Poisoning Attacks on Causal Deep Reinforcement Learning
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318171.pdf (Publisher’s version ) (Open Access)ESORICS 202
Detection of human cytomegalovirus cell-free DNA in pregnant women with symptomatically infected fetuses: proof-of-concept study.
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318201.pdf (Publisher’s version ) (Open Access)OBJECTIVE: To evaluate the presence and levels of cytomegalovirus (CMV) cell-free DNA (cfDNA) fragments in women pregnant with a fetus with symptomatic congenital CMV (cCMV). METHODS: The study comprised nine women whose fetuses were diagnosed with cCMV between June 2019 and July 2024 at 20 + 4 to 34 + 1 weeks' gestation (n = 8) or neonatally (n = 1) after primary or non-primary maternal infection. In eight women, cfDNA sequencing data from a single timepoint were analyzed, either retrospectively, on data generated from 11-13 weeks' gestation (n = 5) or prospectively, on data generated from 20-26 weeks' gestation (n = 3), upon the diagnosis of cCMV. In one woman (Case 6), CMV-cfDNA analysis was performed at four timepoints: at 12 + 5 weeks (routine non-invasive prenatal testing); 23 + 3 weeks (cCMV diagnosis); and 30 min and 12 h after termination of pregnancy (TOP) at 23 + 6 weeks. RESULTS: CMV-cfDNA was detectable in all cases. Mostly low levels of CMV-cfDNA were observed in samples obtained at 11-13 weeks' gestation and consistently high levels of CMV-cfDNA were present in samples obtained at cCMV diagnosis. In Case 6, the level of maternal CMV-cfDNA decreased substantially in the samples tested after TOP, compared with samples obtained before TOP. CONCLUSIONS: Low levels of CMV-cfDNA detected between 11 and 13 weeks may be a biomarker for severe fetal cCMV. CMV-cfDNA analysis in the first trimester could be of added value in CMV screening, particularly for non-primary maternal infections that cannot be identified using other methods. However, as CMV-cfDNA is detectable in many pregnant women in the first trimester, further studies are needed to determine the predictive value of CMV-cfDNA as a biomarker for the development of severe fetal cCMV. High levels of CMV-cfDNA at fetal cCMV diagnosis and low levels directly after TOP suggest that the level of CMV-cfDNA in maternal plasma may not necessarily reflect an active maternal infection, but could indicate a placental infection. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.01 april 202
Coping with loss. Stability of mass transfer from post-main-sequence donor stars (Corrigendum)
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317260.pdf (Publisher’s version ) (Open Access
Positive Experiences with the Use of an eHealth Smartphone Application During the Treatment of an Abdominal Aortic Aneurysm
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312571.pdf (Publisher’s version ) (Closed access
Antihypertensive Medication Category Prescriptions and Blood Pressure Control in African Surinamese and Ghanaian Migrants with Hypertension in Amsterdam, The Netherlands: The HELIUS Study.
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315914.pdf (Publisher’s version ) (Open Access)West African (WA) migrants in Europe have higher hypertension rates than the host populations. For African migrants, guidelines recommend diuretics and/or calcium channel blockers (CCB) for primary cardiovascular disease prevention, but data on antihypertensive medication (AHM) prescription patterns or related hypertension control rates are lacking. We assessed AHM prescription patterns and its relation to hypertension control among hypertensive WA migrants in the Netherlands compared to the host population. Cross-sectional data from WA or Dutch origin participants from the HELIUS study were used. Participants with treated hypertension and without diabetes, cardiovascular disease, or microalbuminuria were selected. We used logistic and linear regression analyses to assess the association between AHM categories and hypertension control rates (systolic blood pressure (BP) ≤ 140 mmHg and diastolic BP ≤ 90 mmHg) and the systolic BP levels. We compared 999 WA participants and 314 Dutch participants. Hypertension control rates were lower in the WA origin compared to Dutch origin participants (44.3% versus 58.0%, p < 0.001). For WA participants, prescription rates for any AHM category were: CCB (54.8%), diuretics (18.5%) beta-blocking agents (27.3%) and renin-angiotensin system blockers (52.6%). Prescription rates were higher for CCB and similar for diuretics compared to the Dutch participants. Neither CCB nor diuretics were associated with better control rates. Compared to Dutch participants, West African participants had similar diuretic prescriptions but significantly higher prescriptions for CCB. However, neither medications was associated with better hypertension control. Future research should explore physician and patient factors to improve hypertension control.01 januari 202