Diversity in the oligodendrocyte lineage: Plasticity or heterogeneity?

Heterogeneity is a widely recognized phenomenon within the majority of cell types in the body including cells of the central nervous system (CNS). The heterogeneity of neurons based on their distinct transmission modes and firing patterns has been recognized for decades, and is necessary to coordinate the immense variety of functions of the CNS. More recently, heterogeneity in glial cells has been identified, including heterogeneity in oligodendrocyte progenitor cells (OPCs) and oligodendrocytes. OPC subpopulations have been described based on their developmental origin, anatomical location in the grey or white matter, and expression of surface receptors. Oligodendrocytes are categorised according to differences in gene expression, myelinogenic potential, and axon specificity. Much of what is described as heterogeneity in oligodendrocyte lineage cells (OLCs) is based on phenotypic differences. However, without evidence for functional differences between putative subgroups of OLCs, distinguishing heterogeneity from plasticity and lineage state is difficult. Identifying functional differences between phenotypically distinct groups are therefore necessary for a deeper understanding of the role of OLCs in health and disease.The authors acknowledge the support of funding from the UK Multiple Sclerosis Society, MedImmune, The Adelson Medical Research Foundation and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute. SF and MFEH have been recipients of Wellcome Trust funded PhD studentships

The fatty acid binding protein FABP7 is required for optimal oligodendrocyte differentiation during myelination but not during remyelination.

The major constituents of the myelin sheath are lipids, which are made up of fatty acids (FAs). The hydrophilic environment inside the cells requires FAs to be bound to proteins, preventing their aggregation. Fatty acid binding proteins (FABPs) are one class of proteins known to bind FAs in a cell. Given the crucial role of FAs for myelin sheath formation we investigated the role of FABP7, the major isoform expressed in oligodendrocyte progenitor cells (OPCs), in developmental myelination and remyelination. Here, we show that the knockdown of Fabp7 resulted in a reduction of OPC differentiation in vitro. Consistent with this result, a delay in developmental myelination was observed in Fabp7 knockout animals. This delay was transient with full myelination being established before adulthood. FABP7 was dispensable for remyelination, as the knockout of Fapb7 did not alter remyelination efficiency in a focal demyelination model. In summary, while FABP7 is important in OPC differentiation in vitro, its function is not crucial for myelination and remyelination in vivo.This work was supported by grants from the UK Multiple Sclerosis Society, the Adelson Medical Research Foundation, the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute. AGF was also supported by an ECTRIMS postdoctoral fellowship from July 2018. SF and TB were also supported by a Wellcome-Trust PhD studentship

Expression of calpain-calpastatin system (CCS) member proteins in human lymphocytes of young and elderly individuals; pilot baseline data for the CALPACENT project.

Ubiquitous system of regulatory, calcium-dependent, cytoplasmic proteases – calpains – and their endogenous inhibitor – calpastatin – is implicated in the proteolytic regulation of activation, proliferation, and apoptosis of many cell types. However, it has not been thoroughly studied in resting and activated human lymphocytes yet, especially in relation to the subjects’ ageing process. The CALPACENT project is an international (Polish-Italian) project aiming at verifying the hypothesis of the role of calpains in the function of peripheral blood immune cells of Polish (Pomeranian) and Italian (Sicilian) centenarians, apparently relatively preserved in comparison to the general elderly population. In this preliminary report we aimed at establishing and comparing the baseline levels of expression of μ- and m-calpain and calpastatin in various, phenotypically defined, populations of human peripheral blood lymphocytes for healthy elderly Sicilians and Poles, as compared to these values observed in young cohort

Problems and Pitfalls of Identifying Remyelination in Multiple Sclerosis.

Regenerative medicines that promote remyelination in multiple sclerosis (MS) are making the transition from laboratory to clinical trials. While animal models provide the experimental flexibility to analyze mechanisms of remyelination, here we discuss the challenges in understanding where and how remyelination occurs in MS.The authors acknowledge the following support: The UK Multiple Sclerosis Society (RTK, CZ, RJMF), The Adelson Medical Research Foundation (DSR, DEB, RJMF), Intramural Research Program of NINDS/NIH (DSR), European Research Council (ERC) under the European Union Horizon 2020 Re- search and Innovation Program (RTK), The Lister Institute (RTK), and a core support grant from the Wellcome and MRC to the Wellcome-Medical Research Council Cambridge Stem Cell Institute (RTK, RJMF)

Estimation of coronary artery hyperemic blood flow based on arterial lumen volume using angiographic images

The purpose of this study is to develop a method to estimate the hyperemic blood flow in a coronary artery using the sum of the distal lumen volumes in a swine animal model. The limitations of visually assessing coronary artery disease are well known. These limitations are particularly important in intermediate coronary lesions where it is difficult to determine whether a particular lesion is the cause of ischemia. Therefore, a functional measure of stenosis severity is needed using angiographic image data. Coronary arteriography was performed in 10 swine (Yorkshire, 25–35 kg) after power injection of contrast material into the left main coronary artery. A densitometry technique was used to quantify regional flow and lumen volume in vivo after inducing hyperemia. Additionally, 3 swine hearts were casted and imaged post-mortem using cone-beam CT to obtain the lumen volume and the arterial length of corresponding coronary arteries. Using densitometry, the results showed that the stem hyperemic flow (Q) and the associated crown lumen volume (V) were related by Q = 159.08 V3/4 (r = 0.98, SEE = 10.59 ml/min). The stem hyperemic flow and the associated crown length (L) using cone-beam CT were related by Q = 2.89 L (r = 0.99, SEE = 8.72 ml/min). These results indicate that measured arterial branch lengths or lumen volumes can potentially be used to predict the expected hyperemic flow in an arterial tree. This, in conjunction with measured hyperemic flow in the presence of a stenosis, could be used to predict fractional flow reserve based entirely on angiographic data

"Meaning" as a sociological concept: A review of the modeling, mapping, and simulation of the communication of knowledge and meaning

The development of discursive knowledge presumes the communication of meaning as analytically different from the communication of information. Knowledge can then be considered as a meaning which makes a difference. Whereas the communication of information is studied in the information sciences and scientometrics, the communication of meaning has been central to Luhmann's attempts to make the theory of autopoiesis relevant for sociology. Analytical techniques such as semantic maps and the simulation of anticipatory systems enable us to operationalize the distinctions which Luhmann proposed as relevant to the elaboration of Husserl's "horizons of meaning" in empirical research: interactions among communications, the organization of meaning in instantiations, and the self-organization of interhuman communication in terms of symbolically generalized media such as truth, love, and power. Horizons of meaning, however, remain uncertain orders of expectations, and one should caution against reification from the meta-biological perspective of systems theory

Risks and opportunities of open-source generative AI

Applications of Generative AI (Gen AI) are expected to revolutionize a number of different areas, ranging from science & medicine to education. The potential for these seismic changes has triggered a lively debate about the potential risks of the technology, and resulted in calls for tighter regulation, in particular from some of the major tech companies who are leading in AI development. This regulation is likely to put at risk the budding field of open-source generative AI. Using a three-stage framework for Gen AI development (near, mid and long-term), we analyze the risks and opportunities of open-source generative AI models with similar capabilities to the ones currently available (near to mid-term) and with greater capabilities (long-term). We argue that, overall, the benefits of open-source Gen AI outweigh its risks. As such, we encourage the open sourcing of models, training and evaluation data, and provide a set of recommendations and best practices for managing risks associated with open-source generative AI

A systematic review of the evidence for single stage and two stage revision of infected knee replacement

BACKGROUND: Periprosthetic infection about the knee is a devastating complication that may affect between 1% and 5% of knee replacement. With over 79 000 knee replacements being implanted each year in the UK, periprosthetic infection (PJI) is set to become an important burden of disease and cost to the healthcare economy. One of the important controversies in treatment of PJI is whether a single stage revision operation is superior to a two-stage procedure. This study sought to systematically evaluate the published evidence to determine which technique had lowest reinfection rates. METHODS: A systematic review of the literature was undertaken using the MEDLINE and EMBASE databases with the aim to identify existing studies that present the outcomes of each surgical technique. Reinfection rate was the primary outcome measure. Studies of specific subsets of patients such as resistant organisms were excluded. RESULTS: 63 studies were identified that met the inclusion criteria. The majority of which (58) were reports of two-stage revision. Reinfection rated varied between 0% and 41% in two-stage studies, and 0% and 11% in single stage studies. No clinical trials were identified and the majority of studies were observational studies. CONCLUSIONS: Evidence for both one-stage and two-stage revision is largely of low quality. The evidence basis for two-stage revision is significantly larger, and further work into direct comparison between the two techniques should be undertaken as a priority

Momentum meets value investing in a small European market

In this paper, we investigate two prominent market anomalies documented in the finance literature – the momentum effect and value-growth effect. We conduct an out- of-sample test to the link between these two anomalies recurring to a sample of Portuguese stocks during the period 1988–2015. We find that the momentum of value and growth stocks is significantly different: growth stocks exhibit a much larger momentum than value stocks. A combined value and momentum strategy can generate statistically significant excess annual returns of 10.8%. These findings persist across several holding periods up to a year. Moreover, we show that macroeconomic variables fail to explain value and momentum of individual and combined returns. Collectively, our results contradict market efficiency at the weak form and pose a challenge to existing asset pricing theories.info:eu-repo/semantics/publishedVersio