| 1. |
- Bergström, Anders, et al.
(author)
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Origins and genetic legacy of prehistoric dogs
- 2020
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 370:6516, s. 557-563
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Journal article (peer-reviewed)abstract
- Dogs were the first domestic animal, but little is known about their population history and to what extent it was linked to humans. We sequenced 27 ancient dog genomes and found that all dogs share a common ancestry distinct from present-day wolves, with limited gene flow from wolves since domestication but substantial dog-to-wolf gene flow. By 11,000 years ago, at least five major ancestry lineages had diversified, demonstrating a deep genetic history of dogs during the Paleolithic. Coanalysis with human genomes reveals aspects of dog population history that mirror humans, including Levant-related ancestry in Africa and early agricultural Europe. Other aspects differ, including the impacts of steppe pastoralist expansions in West and East Eurasia and a near-complete turnover of Neolithic European dog ancestry.
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| 2. |
- Ebersole, Charles R., et al.
(author)
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Many Labs 5: Testing Pre-Data-Collection Peer Review as an Intervention to Increase Replicability
- 2020
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In: Advances in Methods and Practices in Psychological Science. - : Sage. - 2515-2467 .- 2515-2459. ; 3:3, s. 309-331
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Journal article (peer-reviewed)abstract
- Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3-9; median total sample = 1,279.5, range = 276-3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (Delta r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00-.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19-.50).
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| 3. |
- Hermann, Florian M., et al.
(author)
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An insulin hypersecretion phenotype precedes pancreatic beta cell failure in MODY3 patient-specific cells
- 2023
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In: Cell Stem Cell. - : Elsevier. - 1934-5909 .- 1875-9777. ; 30:1, s. 38-51
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Journal article (peer-reviewed)abstract
- MODY3 is a monogenic hereditary form of diabetes caused by mutations in the transcription factor HNF1A. The patients progressively develop hyperglycemia due to perturbed insulin secretion, but the pathogenesis is unknown. Using patient-specific hiPSCs, we recapitulate the insulin secretion sensitivity to the membrane depolarizing agent sulfonylurea commonly observed in MODY3 patients. Unexpectedly, MODY3 patient -specific HNF1A+/R272C R cells hypersecrete insulin both in vitro and in vivo after transplantation into mice. Consistently, we identified a trend of increased birth weight in human HNF1A mutation carriers compared with healthy siblings. Reduced expression of potassium channels, specifically the KATP channel, in MODY3 0 cells, increased calcium signaling, and rescue of the insulin hypersecretion phenotype by pharmacological targeting ATP-sensitive potassium channels or low-voltage-activated calcium channels suggest that more efficient membrane depolarization underlies the hypersecretion of insulin in MODY3 0 cells. Our findings identify a pathogenic mechanism leading to 0 cell failure in MODY3.
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| 4. |
- Hermann, Florian M., et al.
(author)
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An insulin hypersecretion phenotype precedes pancreatic β cell failure in MODY3 patient-specific cells
- 2023
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In: Cell Stem Cell. - : Elsevier BV. - 1934-5909. ; 30:1, s. 8-51
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Journal article (peer-reviewed)abstract
- MODY3 is a monogenic hereditary form of diabetes caused by mutations in the transcription factor HNF1A. The patients progressively develop hyperglycemia due to perturbed insulin secretion, but the pathogenesis is unknown. Using patient-specific hiPSCs, we recapitulate the insulin secretion sensitivity to the membrane depolarizing agent sulfonylurea commonly observed in MODY3 patients. Unexpectedly, MODY3 patient-specific HNF1A+/R272C β cells hypersecrete insulin both in vitro and in vivo after transplantation into mice. Consistently, we identified a trend of increased birth weight in human HNF1A mutation carriers compared with healthy siblings. Reduced expression of potassium channels, specifically the KATP channel, in MODY3 β cells, increased calcium signaling, and rescue of the insulin hypersecretion phenotype by pharmacological targeting ATP-sensitive potassium channels or low-voltage-activated calcium channels suggest that more efficient membrane depolarization underlies the hypersecretion of insulin in MODY3 β cells. Our findings identify a pathogenic mechanism leading to β cell failure in MODY3.
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| 5. |
- Jandrić, Petar, et al.
(author)
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Teaching in the Age of Covid-19
- 2020
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In: Postdigital Science and Education. - : Springer Science and Business Media LLC. - 2524-4868 .- 2524-485X. ; 2:3, s. 1069-1230
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Journal article (other academic/artistic)abstract
- A collection of 84 author's testimonies and workspace photographs between 18 March and 5 May 2020.
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| 6. |
- Jandrić, Petar, et al.
(author)
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Teaching in the Age of Covid-19 : The New Normal
- 2022
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In: Postdigital Science and Education. - : Springer Science and Business Media LLC. - 2524-485X .- 2524-4868. ; 4:3, s. 877-1015
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Journal article (peer-reviewed)abstract
- On 17 March 2020, Postdigital Science and Education launched a call for testimonies about teaching and learning during very frst Covid-19 lockdowns. The resulting article, ‘Teaching in the Age of Covid-19’ (attached), presents 81 written testimonies and 80 workspace photographs submitted by 84 authors from 19 countries. On 17 March 2021, Postdigital Science and Education launched a call for a sequel article of testimonies about teaching and learning during very first Covid-19 lockdowns. The resulting article, ‘Teaching in the Age of Covid-19—1 Year Later’(attached), consists of 74 textual testimonies and 76 workspace photographs submitted by 77 authors from 20 countries.These two articles have been downloaded almost 100,000 times and have been cited more than 100 times. This shows their value as historical documents. Recent analyses, such as ‘Teaching in the Age of Covid-19—A Longitudinal Study ’(attached), also indicate their strong potential for educational research. As the Covid-19 pandemic seems to wind down, pandemic experiences have entered the mainstream. They shape all educational research of today and arguably do not require special treatment. Yet, our unique series of pandemic testimonies provides a unique opportunity to longitudinally trace what happens to the same people over the years—and this opportunity should not be missed.Today, we launch a call for fnal sequel: Teaching in the Age of Covid-19—The New Normal. In this sequel, we would like to hear about ways in which you—contributors to the previous articles—have established your own new normal. We hope that this will be the last iteration in this series of testimony articles. Unless the world faces another strong pandemic outburst, we would like to end the series with this last article.
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| 7. |
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| 8. |
- Kajtez, Janko, et al.
(author)
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Overlap microtubules link sister k-fibres and balance the forces on bi-oriented kinetochores.
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- During metaphase, forces on kinetochores are exerted by k-fibres, bundles of microtubules that end at the kinetochore. Interestingly, non-kinetochore microtubules have been observed between sister kinetochores, but their function is unknown. Here we show by laser-cutting of a k-fibre in HeLa and PtK1 cells that a bundle of non-kinetochore microtubules, which we term 'bridging fibre', bridges sister k-fibres and balances the interkinetochore tension. We found PRC1 and EB3 in the bridging fibre, suggesting that it consists of antiparallel dynamic microtubules. By using a theoretical model that includes a bridging fibre, we show that the forces at the pole and at the kinetochore depend on the bridging fibre thickness. Moreover, our theory and experiments show larger relaxation of the interkinetochore distance for cuts closer to kinetochores. We conclude that the bridging fibre, by linking sister k-fibres, withstands the tension between sister kinetochores and enables the spindle to obtain a curved shape.
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| 9. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 10. |
- Novak, Ivana
(author)
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Molecular architecture of meiotic chromosomes
- 2006
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Doctoral thesis (other academic/artistic)abstract
- Faithful chromosome segregation at each cell division is essential as the formation of cells with an abnormal number of chromosomes (aneuploid cells) can result in infertility, developmental defects or cancer. Aneuploidy occurs in approximately 20% of all conceptions, causing infertility and embryo death. Chromosomal disorders are the most common known cause of mental retardation, e.g. Downs syndrome, affecting 0,3% of all newborns. Meiosis is a highly specialized germ cell specific cell division that generates genetically diverse haploid gametes. The aim of this thesis was to study the functions of a set of structural and regulatory proteins that are associated with the meiotic chromosomes. Mammalian meiotic chromosomes at meiosis I are organised and supported by several protein structures including synaptonemal and cohesin complexes. The synaptonernal complex (SC), formed only in meiosis, promotes synapsis and recombination between the homologues. The SC is composed of two axial elements (AEs) and the central element (CE) connected by transverse filaments (TFs). The AEs are composed of Sycp2 and Sycp3 whereas the TFs are formed by Sycp1. The cohesin complexes are formed by Smc1α, Smc3, Scc1/Rad21 and Scc3/SA1 or SA2 and three meiosis-specific subunits Smc1β, Rec8 and Stag3 The cohesin complexes are important for sister chromatid pairing and separation during mitosis and meiosis and are likely to be the key organisers of the chromatin loop arrays along the meiotic chromosome axis. So far, it has been difficult to reproduce the germ cell differentiation process in vitro using cell culture models. Our attempt to differentiate embryonic stem cells (ESCs) to germ cells, in order to analyze meiotic chromosome architecture in vitro, revealed the inaccurate meiotic development of germ celllike cells derived from ESCs in culture. This suggests that, while several aspects of the germ cell differentiation process can be reproduced in vitro, more work is required to validate the meiotic cell division process in the identified germ cell-like cells. The Sycp3-deficient mouse strain was used as a model to monitor the integrity of the meiotic chromosome axis. We found that the cohesins disassembled prematurely in the absence of Sycp3. This supports a model where Sycp3 has a structural role in maintaining, but not establishing the cohesin core. Mutant mice lacking both Sycp3 and Smc1β p proteins have provided novel insights into the organization of the meiotic chromosomes. It was shown that loss of Sycp3 or Smc1β impairs the structural integrity of the meiotic chromosomes by affecting the length of the chromosome axes. We showed that different cohesin complexes coexist along the meiotic chromosome axis and generate an axial core that physically anchors the chromatin loops to the axes. Analysis of chromosome asynapsis and crossover patterns in Sycp3-/-Smc1β-/- revealed that this loss affects the accuracy of chromosome segregation and activates two independent checkpoints that eliminate damaged oocytes. Meiotic checkpoints and DNA damage repair are often hypothesized to be regulated from the central region of the SC. Previously, no proteins have been assigned to central region of the SC. We identified three novel central element (CE) proteins, Syce1, Sycp2 and Tex12. We found that Sycp1 is essential for their integration into the SC. Results revealed a novel molecular network within the CE.
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