International Centre for the Study of Historical consciousness

My social studies education friend thought I had proposed a program of “history awareness.” My graduate student feared I was setting myself up in competition with Hayden White’s History of Consciousness program. My historiographically oriented colleague detected tones of 19th century German ideal- ism. Yikes! And I thought it was such an innocent title

Benchmarks of Historical Thinking: First Steps

Although historical thinking has been the subject of a substantial body of recent research, few attempts explicitly apply the results on a large scale in North America. This article, a narrative inquiry, examines the first stages of a multi-year, Canada- wide project to reform history education through the development of classroom- based assessments. The study is based on participant-observations, documents gen- erated by the project, and interviews, questionnaires, and correspondence with parti- cipants. The authors find impediments – apparently surmountable – in teachers’ ap- plication of potentially difficult concepts, and in their organizational resistance. Key words: assessment, historical thinking, history education, narrative inquiry Bien que la pensée historique ait été récemment le sujet de nombreuses recherches, peu d’entre elles tentent explicitement d’en appliquer les résultats sur une large échelle en Amérique du Nord. Dans cet article, l’auteur décrit les premières étapes d’un projet canadien de plusieurs années visant à réformer les cours d’histoire en recourant à des évaluations basées sur les classes. L’étude s’appuie sur l’observation des participants, des documents générés par le projet ainsi que des entrevues, des questionnaires et de la correspondance avec les participants. Les auteurs identifient des obstacles – apparemment surmontables – à la mise en application par les enseignants de concepts potentiellement difficiles et notent leur résistance organisa- tionnelle. Mots clés : évaluation, pensée historique, cours d’histoire, recherche descriptive

Ancestral Origin of the ATTCT Repeat Expansion in Spinocerebellar Ataxia Type 10 (SCA10)

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disease characterized by cerebellar ataxia and seizures. The disease is caused by a large ATTCT repeat expansion in the ATXN10 gene. The first families reported with SCA10 were of Mexican origin, but the disease was soon after described in Brazilian families of mixed Portuguese and Amerindian ancestry. The origin of the SCA10 expansion and a possible founder effect that would account for its geographical distribution have been the source of speculation over the last years. To unravel the mutational origin and spread of the SCA10 expansion, we performed an extensive haplotype study, using closely linked STR markers and intragenic SNPs, in families from Brazil and Mexico. Our results showed (1) a shared disease haplotype for all Brazilian and one of the Mexican families, and (2) closely-related haplotypes for the additional SCA10 Mexican families; (3) little or null genetic distance in small normal alleles of different repeat sizes, from the same SNP lineage, indicating that they are being originated by a single step mechanism; and (4) a shared haplotype for pure and interrupted expanded alleles, pointing to a gene conversion model for its generation. In conclusion, we show evidence for an ancestral common origin for SCA10 in Latin America, which might have arisen in an ancestral Amerindian population and later have been spread into the mixed populations of Mexico and Brazil

Workshop on accounting for fishers and other stakeholders’ perceptions of the dynamics of fish stocks in ICES advice (WKAFPA)

The objective of the Workshop on accounting for fishers and other stakeholders’ perceptions of the dynamics of fish stocks in ICES advice (WKAFPA) was to identify where and how stake- holder information could be incorporated in the ICES fisheries advice process. It adopted an operational definition of the concept of perception, where perceptions result from observations, interpreted in light of experience, that can be supported by data, information and knowledge to generate evidence about them. Stakeholder information can be either structured (e.g. routinely collected information in a standardized format) or unstructured (e.g. experiential information) and either of those can inform decisions made during the production of ICES advice. Most notably, the group identified there was a need to engage with stakeholders earlier in the process, i.e. before benchmarks meetings take place and before preliminary assessment results are used as the basis to predict total allowable catches for upcoming advice (Figure 4.2). It was therefore recommended to include in the ICES process the organisation of pre-bench- mark/roadmap workshops where science and data needs of upcoming benchmarks can be iden- tified, followed by making arrangements how scientists and stakeholders can collaborate to ac- cess, prepare for use (where relevant) and document the structured and unstructured infor- mation well ahead of the benchmark meetings. It was also recommended to organise ‘sense-checking’ sessions with stakeholders when prelim- inary assessments are available but not yet used as the basis for advisory production. This would allow stakeholders and assessment scientists to verify available knowledge and data against stock perceptions and provide additional considerations relevant for the production of TAC ad- vice. Next to these two additional activities, it is recommended that communication on differ- ences in stakeholder perception or data derived perceptions are communicated within the ICES assessment reports as well as in the ICES advice in a transparent manner. Not only should dif- ferences or similarities be documented and communicated, in those cases where there are differ- ences in perception between ICES stock assessments and stakeholders, a working group, external to the assessment working groups, should evaluate these differences and describe whether these differences can be logically explained or require further investigation. This outcome of this pro- cess may potentially lead to new data collection or additional analyses suitable for input to benchmarks. Essential in this entire process is making sure the same language is spoken between scientists and stakeholders, that there are clear and transparent processes in place on how to deal with stakeholder information and communicate clearly how this information is used in the prepara- tion of ICES advice.info:eu-repo/semantics/publishedVersio

Common coding variant in SERPINA1 increases the risk for large artery stroke

Large artery atherosclerotic stroke (LAS) shows substantial heritability not explained by previous genome-wide association studies. Here, we explore the role of coding variation in LAS by analyzing variants on the HumanExome BeadChip in a total of 3,127 cases and 9,778 controls from Europe, Australia, and South Asia. We report on a nonsynonymous single-nucleotide variant in serpin family A member 1 (SERPINA1) encoding alpha-1 antitrypsin [AAT; p.V213A; P = 5.99E-9, odds ratio (OR) = 1.22] and confirm histone deacetylase 9 (HDAC9) as a major risk gene for LAS with an association in the 3?-UTR (rs2023938; P = 7.76E-7, OR = 1.28). Using quantitative microscale thermophoresis, we show that M1 (A213) exhibits an almost twofold lower dissociation constant with its primary target human neutrophil elastase (NE) in lipoprotein-containing plasma, but not in lipid-free plasma. Hydrogen/deuterium exchange combined with mass spectrometry further revealed a significant difference in the global flexibility of the two variants. The observed stronger interaction with lipoproteins in plasma and reduced global flexibility of the Val-213 variant most likely improve its local availability and reduce the extent of proteolytic inactivation by other proteases in atherosclerotic plaques. Our results indicate that the interplay between AAT, NE, and lipoprotein particles is modulated by the gate region around position 213 in AAT, far away from the unaltered reactive center loop (357-360). Collectively, our findings point to a functionally relevant balance between lipoproteins, proteases, and AAT in atherosclerosis

Workshop on Assessing the Impact of Fishing on Oceanic Carbon (WKFISHCARBON; outputs from 2023 meeting)

Rapports Scientifiques du CIEM. Volume 6, nº 12The Workshop on Assessing the Impact of Fishing on Oceanic Carbon (WKFISHCARBON) was set up to provide ICES and stakeholders with a summary of knowledge on the role of fishing in the process of carbon budgets, sequestration and footprint in the ocean. The workshop addressed the potential impact of fishing on the biological carbon pump (BCP), the possible impacts of bottom trawling on carbon stores in the seabed, as well as considering emissions from fishing vessels. The overall aim was to generate proposals on how to develop an ICES approach to fishing and its role in the ocean carbon budget, and to develop a roadmap for a way forward. The main findings were that knowledge of the BCP in the open ocean was reasonably well developed, but that key gaps existed. In particular, information on the biomass of mesopelagic fish and other biota, and of some of the key processes e.g. fluxes and fish bioenergetics. Knowledge is much weaker for the BCP in shelf seas, where the bulk of fishing occurs. In particular, while biomass of fish was often well quantified, unlike the open ocean, the understanding of the important processes was lacking, particularly for the fate of faecal pellets and deadfall at the seabed. There is extensive scientific knowledge of the impact of fishing on the seabed, but what is un-clear is what it means for seabed carbon storage. There have been numbers of studies, which give a very divided view on this. There has also been open controversy about this in the literature. Physical disturbance to the seabed from fishing can affect sediment transport and has the potential to facilitate remineralization, but precise impacts will depend on habitat, fishing métier, and other environmental factors. From this, it is clear that more research is needed to resolve the controversy, and to quantify the impacts from different fishing gears and on different substrates or habitats in terms of carbon storage. There has been much more research on minimizing fuel use by fishing vessels, and hence emissions, but this has mainly focused on fuel efficiency, fuel use per unit of landed catch, and less on the total emissions. Baselines for fuel use are available at the global level, but are lacking at the national and vessel level. There is a need for standardization of methodologies and protocols, and for improving the uptake of fuel conservation measures by industry, as well as for improving the uptake of existing and potential fuel conservation and efficiency measures by industry. Finally, a roadmap was proposed to develop research and synthesis, on the understandings of the processes involved, the metrics and how to translate this into possible advice for policy-makers. To that end, a further workshop was proposed in 2024.info:eu-repo/semantics/publishedVersio

A de novo paradigm for male infertility

Funding Information: (DFG, CRU326) to C.F. and F.T. This project was also supported in part by funding from the Australian National Health and Medical Research Council (APP1120356) to M.K.O.B., by grants from the National Institutes of Health of the United States of America (R01HD078641 to D.F.C. and K.I.A., P50HD096723 to D.F.C.) and from the Biotechnology and Biological Sciences Research Council (BB/S008039/1) to D.J.E. Funding Information: We are grateful for the participation of all patients and their parents in this study. We thank Laurens van de Wiel (Radboudumc), Sebastian Judd-Mole (Monash University), Arron Scott and Bryan Hepworth (Newcastle University) for technical support, and Margot J Wyrwoll (University of Münster) for help with handling MERGE samples and data. This project was funded by The Netherlands Organization for Scientific Research (918-15-667) to J.A.V. as well as an Investigator Award in Science from the Wellcome Trust (209451) to J.A.V. a grant from the Catherine van Tussenbroek Foundation to M.S.O. a grant from MERCK to R.S. a UUKi Rutherford Fund Fellowship awarded to B.J.H. and the German Research Foundation Clinical Research Unit “Male Germ Cells” Publisher Copyright: © 2022, The Author(s).De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de novo mutations play an important role in severe male infertility and explain a portion of the genetic causes of this understudied disorder. To test this hypothesis, we utilize trio-based exome sequencing in a cohort of 185 infertile males and their unaffected parents. Following a systematic analysis, 29 of 145 rare (MAF < 0.1%) protein-altering de novo mutations are classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of loss-of-function de novo mutations in loss-of-function-intolerant genes (p-value = 1.00 × 10−5) in infertile men compared to controls. Additionally, we detected a significant increase in predicted pathogenic de novo missense mutations affecting missense-intolerant genes (p-value = 5.01 × 10−4) in contrast to predicted benign de novo mutations. One gene we identify, RBM5, is an essential regulator of male germ cell pre-mRNA splicing and has been previously implicated in male infertility in mice. In a follow-up study, 6 rare pathogenic missense mutations affecting this gene are observed in a cohort of 2,506 infertile patients, whilst we find no such mutations in a cohort of 5,784 fertile men (p-value = 0.03). Our results provide evidence for the role of de novo mutations in severe male infertility and point to new candidate genes affecting fertility.publishersversionpublishe