| 1. |
- Brandhorst, Daniel, et al.
(författare)
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Multicenter Assessment of Animal-free Collagenase AF-1 for Human Islet Isolation
- 2017
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Ingår i: Cell Transplantation. - : Sage Publications. - 0963-6897 .- 1555-3892. ; 26:10, s. 1688-1693
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Tidskriftsartikel (refereegranskat)abstract
- Animal-free (AF) SERVA Collagenase AF-1 and Neutral Protease (NP) AF GMP Grade have recently become available for human islet isolation. This report describes the initial experiences of 3 different islet transplant centers. Thirty-four human pancreases were digested using 1 vial of the 6 different lots of Collagenase AF-1 (2,000-2,583 PZ-U/vial) supplemented with 4 different lots of NP AF in a range of 50 to 160 DMC-U per pancreas. Isolation, culture, and quality assessment were performed using standard techniques as previously described. All data are presented as mean +/- standard error of the mean (SEM). Variability of pancreas weight was associated with a wide range of collagenase and NP activities, ranging from 12.7 to 46.6 PZ-U/g (26.0 +/- 1.5 PZ-U/g) and 0.4 to 3.0 DMC-U/g (1.5 +/- 0.1 DMC-U/g), respectively. Postpurification islet yield was 296,494 +/- 33,620 islet equivalents (IEQ) equivalent to 3,274 +/- 450 IEQ/g with a purity of 55.9% +/- 3.2%. Quality assessment performed after 2 to 4 d of culture demonstrated a viability of 88.1% +/- 1.5% and a stimulation index of 3.7 +/- 0.7. Eighteen of the 34 preparations were transplanted into type 1 diabetic patients equivalent to a transplantation rate of 52.9%. Six preparations, which were infused into patients as first transplant, could be analyzed and increased the fasting C-peptide level from 0.11 +/- 0.08 pretransplant to 1.23 +/- 0.24 and 2.27 +/- 0.31 ng/mL 3 and 6 mo posttransplant (P < 0.05), respectively. Insulin requirements were simultaneously reduced at the same time from 39.2 +/- 3.8 IU/d before transplantation to 10.8 +/- 4.1 and 4.0 +/- 2.3 IU/d, after 3 and 6 mo posttransplant (P < 0.05), respectively. This study demonstrates the efficiency of AF SERVA Collagenase AF-1 and NP AF for clinical islet isolation and transplantation. The new plant-based production process makes these products a safe new option for the islet field.
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| 2. |
- Frantz, Laurent A. F., et al.
(författare)
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Genomic and archaeological evidence suggests a dual origin of domestic dogs
- 2016
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 352:6290, s. 1228-1231
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Tidskriftsartikel (refereegranskat)abstract
- The geographic and temporal origins of dogs remain controversial. We generated genetic sequences from 59 ancient dogs and a complete (28x) genome of a late Neolithic dog (dated to similar to 4800 calendar years before the present) from Ireland. Our analyses revealed a deep split separating modern East Asian and Western Eurasian dogs. Surprisingly, the date of this divergence (similar to 14,000 to 6400 years ago) occurs commensurate with, or several millennia after, the first appearance of dogs in Europe and East Asia. Additional analyses of ancient and modern mitochondrial DNA revealed a sharp discontinuity in haplotype frequencies in Europe. Combined, these results suggest that dogs may have been domesticated independently in Eastern and Western Eurasia from distinct wolf populations. East Eurasian dogs were then possibly transported to Europe with people, where they partially replaced European Paleolithic dogs.
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| 3. |
- Princen, Katrien, et al.
(författare)
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Pharmacological modulation of septins restores calcium homeostasis and is neuroprotective in models of Alzheimer's disease
- 2024
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Ingår i: SCIENCE. - 0036-8075 .- 1095-9203. ; 384:6699
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Tidskriftsartikel (refereegranskat)abstract
- Abnormal calcium signaling is a central pathological component of Alzheimer's disease (AD). Here, we describe the identification of a class of compounds called ReS19-T, which are able to restore calcium homeostasis in cell-based models of tau pathology. Aberrant tau accumulation leads to uncontrolled activation of store-operated calcium channels (SOCCs) by remodeling septin filaments at the cell cortex. Binding of ReS19-T to septins restores filament assembly in the disease state and restrains calcium entry through SOCCs. In amyloid-beta and tau-driven mouse models of disease, ReS19-T agents restored synaptic plasticity, normalized brain network activity, and attenuated the development of both amyloid-beta and tau pathology. Our findings identify the septin cytoskeleton as a potential therapeutic target for the development of disease-modifying AD treatments.
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| 4. |
- Sandberg, Anne, et al.
(författare)
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Intra- and Extracellular Activities of Dicloxacillin and Linezolid against a Clinical Staphylococcus aureus Strain with a Small-Colony-Variant Phenotype in an In Vitro Model of THP-1 Macrophages and an In Vivo Mouse Peritonitis Model
- 2011
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Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 55:4, s. 1443-1452
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Tidskriftsartikel (refereegranskat)abstract
- The small colony variant (SCV) phenotype of Staphylococcus aureus has been associated with difficult-to-treat infections, reduced antimicrobial susceptibility and intracellular persistence. This study represents a detailed intra- and extracellular investigation of a clinical wild type (WT) S. aureus strain and its counterpart SCV phenotype both in vitro and in vivo, using the THP-1 cell line model and mouse peritonitis model respectively. Both phenotypes infected the mouse peritoneum intra- and extracellularly. The SCV phenotype was less virulent, showed distinct bacterial clearance, reduced multiplication capacity and reduced internalization ability. Some of the SCV infected mice were, however, still culture positive up to 96 h post infection and the phenotype could spread to the mouse kidney and furthermore revert to the more virulent WT phenotype in both the mouse- peritoneum and kidney. The SCV phenotype is therefore, despite reduced virulence, an important player in the S. aureus pathogenesis. In the THP-1 cell line model, both dicloxacillin (DCX) and linezolid (LZD) reduced the intracellular inoculum of both phenotypes by approximately 1-1.5 log10 in vitro, while DCX was considerably more effective against extracellular bacteria. In the mouse peritonitis model, DCX and LZD were also able to control both the intra- and extracellular infection caused by either phenotype. Treatment with a single dose of DCX and LZD was, however, insufficient to clear the SCVs in the kidneys and the risk of recurrent infection remained. This stresses the importance of optimal dosing of the antibiotic when SCVs are present.
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