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"Daniel, Muller"
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Stock dynamics for forecasting material flows-case study for housing in The Netherlands
This article discusses the role of lifestyle in physical material accounting and introduces a new method for simultaneously determining national or regional resource demand and waste generation through estimations of the population and its lifestyle, which is manifested in the stocks of service providing goods, their composition and lifetimes. Improving our comprehension of the stocks in use is essential for environmental policy making because (1) they are becoming the most important resource providers, (2) they are important drivers for resource and energy consumption as well as waste and emission generation, and (3) their magnitudes and dynamics are the parts of the material cycles that is usually least understood. A generic dynamic material flow analysis model is presented and applied for the diffusion of concrete in the Dutch dwelling stock for the period of 1900-2100. Simulation results are illustrated for a standard scenario and a parameter variation. The results show that (1) construction and demolition flows follow a cyclical behaviour, (2) the cycles of construction and demolition flows are phase displaced in the first half of the 21st century, with decreasing construction and increasing demolition, and (3) growth of the dwelling stock is becoming increasingly more material intensive as a growing amount of material is used for replacements. The presented stock dynamics approach can principally be applied for any anthropogenic material stock; however, it is most useful for the examination of metabolic consequences of diffusion processes of durable and fixed capital stocks. Reprinted by permission of Cambridge University Press. An electronic version of this article can be accessed via the internet at http://journals.cambridge.org
Journal Article
Control of Directed Cell Migration In Vivo by Membrane-to-Cortex Attachment
Cell shape and motility are primarily controlled by cellular mechanics. The attachment of the plasma membrane to the underlying actomyosin cortex has been proposed to be important for cellular processes involving membrane deformation. However, little is known about the actual function of membrane-to-cortex attachment (MCA) in cell protrusion formation and migration, in particular in the context of the developing embryo. Here, we use a multidisciplinary approach to study MCA in zebrafish mesoderm and endoderm (mesendoderm) germ layer progenitor cells, which migrate using a combination of different protrusion types, namely, lamellipodia, filopodia, and blebs, during zebrafish gastrulation. By interfering with the activity of molecules linking the cortex to the membrane and measuring resulting changes in MCA by atomic force microscopy, we show that reducing MCA in mesendoderm progenitors increases the proportion of cellular blebs and reduces the directionality of cell migration. We propose that MCA is a key parameter controlling the relative proportions of different cell protrusion types in mesendoderm progenitors, and thus is key in controlling directed migration during gastrulation.
Journal Article
Multiparametric imaging of biological systems by force-distance curve–based AFM
This Review of force-distance curve-based atomic force microscopy highlights the unique capabilities of the technique to simultaneously image the architecture of complex biological systems and map their physical, chemical and biological properties at nanometer resolution.
A current challenge in the life sciences is to understand how biological systems change their structural, biophysical and chemical properties to adjust functionality. Addressing this issue has been severely hampered by the lack of methods capable of imaging biosystems at high resolution while simultaneously mapping their multiple properties. Recent developments in force-distance (FD) curve–based atomic force microscopy (AFM) now enable researchers to combine (sub)molecular imaging with quantitative mapping of physical, chemical and biological interactions. Here we discuss the principles and applications of advanced FD-based AFM tools for the quantitative multiparametric characterization of complex cellular and biomolecular systems under physiological conditions.
Journal Article
Dopaminergic dysfunction and excitatory/inhibitory imbalance in treatment-resistant schizophrenia and novel neuromodulatory treatment
Antipsychotic drugs are the mainstay in the treatment of schizophrenia. However, one-third of patients do not show adequate improvement in positive symptoms with non-clozapine antipsychotics. Additionally, approximately half of them show poor response to clozapine, electroconvulsive therapy, or other augmentation strategies. However, the development of novel treatment for these conditions is difficult due to the complex and heterogenous pathophysiology of treatment-resistant schizophrenia (TRS). Therefore, this review provides key findings, potential treatments, and a roadmap for future research in this area. First, we review the neurobiological pathophysiology of TRS, particularly the dopaminergic, glutamatergic, and GABAergic pathways. Next, the limitations of existing and promising treatments are presented. Specifically, this article focuses on the therapeutic potential of neuromodulation, including electroconvulsive therapy, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and deep brain stimulation. Finally, we propose multivariate analyses that integrate various perspectives of the pathogenesis, such as dopaminergic dysfunction and excitatory/inhibitory imbalance, thereby elucidating the heterogeneity of TRS that could not be obtained by conventional statistics. These analyses can in turn lead to a precision medicine approach with closed-loop neuromodulation targeting the detected pathophysiology of TRS.
Journal Article
Economic evaluation in psychiatric pharmacogenomics: a systematic review
Nowadays, many relevant drug–gene associations have been discovered, but pharmacogenomics (PGx)-guided treatment needs to be cost-effective as well as clinically beneficial to be incorporated into standard health care. To address current challenges, this systematic review provides an update regarding previously published studies, which assessed the cost-effectiveness of PGx testing for the prescription of antidepressants and antipsychotics. From a total of 1159 studies initially identified by literature database querying, and after manual assessment and curation of all of them, a mere 18 studies met our inclusion criteria. Of the 18 studies evaluations, 16 studies (88.89%) drew conclusions in favor of PGx testing, of which 9 (50%) genome-guided interventions were cost-effective and 7 (38.9%) were less costly compared to standard treatment based on cost analysis. More precisely, supportive evidence exists for CYP2D6 and CYP2C19 drug–gene associations and for combinatorial PGx panels, but evidence is limited for many other drug–gene combinations. Amongst the limitations of the field are the unclear explanation of perspective and cost inputs, as well as the underreporting of study design elements, which can influence though the economic evaluation. Overall, the findings of this article demonstrate that although there is growing evidence on the cost-effectiveness of genome-guided interventions in psychiatric diseases, there is still a need for performing additional research on economic evaluations of PGx implementation with an emphasis on psychiatric disorders.
Journal Article
Hydrostatic pressure and the actomyosin cortex drive mitotic cell rounding
What makes cells go round
Forces that drive cell shape changes are fundamental to development. During mitosis, adherent cells change from a flattened to rounded morphology, and this is thought to be necessary for the geometric requirements of cell division. Stewart
et al
. study the forces that drive this shape change. They find that the mitotic rounding force depends both on the actomyosin cytoskeleton and the cell's ability to regulate osmolarity. The rounding force is generated by osmotic pressure, and the actomyosin cortex maintains this rounding pressure against external forces. These results support the idea that in animal cells, the actomyosin cortex behaves as an internal cell wall, directing osmotic expansion to control cell shape.
During mitosis, adherent cells change from a flattened to a rounded morphology, and this is thought to be necessary for the geometric requirements of cell division. Here, the forces that drive this shape change are studied. Mitotic rounding force depends both on the actomyosin cytoskeleton and the cell's ability to regulate osmolarity. The rounding force is generated by osmotic pressure and the actomyosin cortex maintains this rounding pressure against external forces. These results support the idea that in animal cells, the actomyosin cortex behaves like an internal cell wall that directs osmotic expansion to control cell shape.
During mitosis, adherent animal cells undergo a drastic shape change, from essentially flat to round
1
,
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. Mitotic cell rounding is thought to facilitate organization within the mitotic cell and be necessary for the geometric requirements of division
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,
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,
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,
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. However, the forces that drive this shape change remain poorly understood in the presence of external impediments, such as a tissue environment
2
. Here we use cantilevers to track cell rounding force and volume. We show that cells have an outward rounding force, which increases as cells enter mitosis. We find that this mitotic rounding force depends both on the actomyosin cytoskeleton and the cells’ ability to regulate osmolarity. The rounding force itself is generated by an osmotic pressure. However, the actomyosin cortex is required to maintain this rounding force against external impediments. Instantaneous disruption of the actomyosin cortex leads to volume increase, and stimulation of actomyosin contraction leads to volume decrease. These results show that in cells, osmotic pressure is balanced by inwardly directed actomyosin cortex contraction. Thus, by locally modulating actomyosin-cortex-dependent surface tension and globally regulating osmotic pressure, cells can control their volume, shape and mechanical properties.
Journal Article
Quantifying cellular adhesion to extracellular matrix components by single-cell force spectroscopy
Atomic force microscopy (AFM)-based single-cell force spectroscopy (SCFS) enables the quantitative study of cell adhesion under physiological conditions. SCFS probes adhesive interactions of single living cells with substrates such as extracellular matrix (ECM) proteins and other cells. Here we present a protocol to study integrin-mediated adhesion of HeLa cells to collagen type I using SCFS. We describe procedures for (i) functionalization of AFM cantilevers with the lectin concanavalin A and supports with collagen, (ii) cell handling and attachment to the AFM cantilever, (iii) measurement of adhesion forces and (iv) data analysis and interpretation. Although designed to measure HeLa cell adhesion to collagen, the protocol can be modified for other cell lines and ECM proteins. Compared with other SCFS assays (for example, optical tweezer, biomembrane force probe), AFM-based SCFS has a more versatile force detection range, and it can therefore be used to address a broader range of biological questions. The protocol can be completed in 2–3 d.
Journal Article
Analysis of genes contributing to plant-beneficial functions in plant growth-promoting rhizobacteria and related Proteobacteria
The positive effects of root-colonizing bacteria cooperating with plants lead to improved growth and/or health of their eukaryotic hosts. Some of these Plant Growth-Promoting Rhizobacteria (PGPR) display several plant-beneficial properties, suggesting that the accumulation of the corresponding genes could have been selected in these bacteria. Here, this issue was targeted using 23 genes contributing directly or indirectly to established PGPR effects, based on genome sequence analysis of 304 contrasted Alpha- Beta- and Gammaproteobacteria. Most of the 23 genes studied were also found in non-PGPR Proteobacteria and none of them were common to all 25 PGPR genomes studied. However, ancestral character reconstruction indicated that gene transfers -predominantly ancient- resulted in characteristic gene combinations according to taxonomic subgroups of PGPR strains. This suggests that the PGPR-plant cooperation could have established separately in various taxa, yielding PGPR strains that use different gene assortments. The number of genes contributing to plant-beneficial functions increased along the continuum -animal pathogens, phytopathogens, saprophytes, endophytes/symbionts, PGPR- indicating that the accumulation of these genes (and possibly of different plant-beneficial traits) might be an intrinsic PGPR feature. This work uncovered preferential associations occurring between certain genes contributing to phytobeneficial traits and provides new insights into the emergence of PGPR bacteria.
Journal Article
Cognitive and psychosocial function in retired professional hockey players
Background and ObjectiveThe relationship between repeated concussions and neurodegenerative disease has received significant attention, particularly research in postmortem samples. Our objective was to characterise retired professional ice hockey players’ cognitive and psychosocial functioning in relation to concussion exposure and apolipoprotein ε4 status.MethodsAlumni athletes (N=33, aged 34–71 years) and an age-matched sample of comparison participants (N=18) were administered measures of cognitive function and questionnaires concerning psychosocial and psychiatric functioning.ResultsNo significant group differences were found on neuropsychological measures of speeded attention, verbal memory or visuospatial functions, nor were significant differences observed on computerised measures of response speed, inhibitory control and visuospatial problem solving. Reliable group differences in cognitive performance were observed on tests of executive and intellectual function; performance on these measures was associated with concussion exposure. Group differences were observed for cognitive, affective and behavioural impairment on psychosocial questionnaires and psychiatric diagnoses. There was no evidence of differential effects associated with age in the alumni athletes. Possession of an apolipoprotein ε4 allele was associated with increased endorsement of psychiatric complaints, but not with objective cognitive performance.ConclusionsWe found only subtle objective cognitive impairment in alumni athletes in the context of high subjective complaints and psychiatric impairment. Apolipoprotein ε4 status related to psychiatric, but not cognitive status. These findings provide benchmarks for the degree of cognitive and behavioural impairment in retired professional athletes and a point of comparison for future neuroimaging and longitudinal studies.
Journal Article