Advancements in pharmacogenomics have introduced an increasing number of opportunities to bring personalized medicine into clinical practice. Understanding how and when to use this technology to ...guide pharmacotherapy used to treat psychiatric and neurological (neuropsychiatric) conditions remains a challenge for many clinicians. Currently, guidelines exist to assist clinicians in the use of existing genetic information for drug selection and/or dosing for the tricyclic antidepressants, carbamazepine, and phenytoin. Additional language in the product labeling suggests that genetic information may also be useful for determining the starting and target doses, as well as drug interaction potential, for a number of other drugs. In this review, we outline the current status of pharmacogenomic testing for neuropsychiatric drugs as it pertains to information contained in drug labeling, consensus guidelines, and test panels, as well as considerations related to obtaining tests for patients.
Prokaryote–eukaryote interactions are primordial, but host selection of its bacterial community remains poorly understood. Because eukaryote evolution affects numerous traits shaping the ecology of ...their microbiome, we can expect that many evolutionary changes in the former will have the potential to impact on the composition of the latter. Consequently, the more phylogenetically distant the eukaryotic hosts, the more distinct their associated bacterial communities should be. We tested this with plants, by comparing the bacterial communities associated with maize genotypes or other Poaceae. 16S rRNA taxonomic microarray analysis showed that the genetic distance between rhizobacterial communities correlated significantly with the phylogenetic distance (derived from chloroplastic sequences) between Poaceae genotypes. This correlation was also significant when considering specific bacterial populations from all main bacterial divisions, instead of the whole rhizobacterial community. These results indicate that eukaryotic host's evolutionary history can be a significant factor shaping directly the assembly and composition of its associated bacterial compartment.
In recent years, single-molecule force spectroscopy techniques have been used to study how inter- and intramolecular interactions control the assembly and functional state of biomolecular machinery ...in vitro. Here we discuss the problems and challenges that need to be addressed to bring these technologies into living cells and to learn how cellular machinery is controlled in vivo.
•Classification framework of secondary resources was applied to aluminum.•Global secondary aluminum reserves were estimated 413 million tonnes.•Considerable amount of secondary aluminum are ...accumulated in landfill sites.
A classification framework of the secondary resources was applied to evaluate the framework’s applicability and to assess secondary aluminum reserves for 19 countries. Estimated amounts of secondary aluminum reserves in 2010 were 85 million tonnes in the United States, 65 million tonnes in China, 29 million tonnes in Japan, and 413 million tonnes globally. For the United States, its secondary reserves are larger than its primary reserves, although the global primary reserves (28,000 million tonnes) are much larger than the estimated secondary reserves. Considerable amounts of secondary aluminum resources are accumulated in landfill sites. Understanding the sizes of primary and secondary aluminum reserves enables us to extend knowledge of efficient raw material sourcing from a narrow perspective of primary reserves alone to a broader perspective of both primary and secondary reserves, and to progress towards sustainable resource management.
Cell adhesion receptors play a central role in sensing and integrating signals provided by the cellular environment. Thus, understanding adhesive interactions at the cell-biomaterial interface is ...essential to improve the design of implants that should emulate certain characteristics of the cell's natural environment. Numerous cell adhesion assays have been developed; among these, atomic force microscopy-based single-cell force spectroscopy (AFM-SCFS) provides a versatile tool to quantify cell adhesion at physiological conditions. Here we discuss how AFM-SCFS can be used to quantify the adhesion of living cells to biomaterials and give examples of using AFM-SCFS in tissue engineering and regenerative medicine. We anticipate that in the near future, AFM-SCFS will be established in the biomaterial field as an important technique to quantify cell-biomaterial interactions and thereby will contribute to the optimization of implants, scaffolds, and medical devices.
•Long-term assessment of 250 years of agricultural and forest cover change.•Meta-analysis of 66 publications describing 102 locations across the Carpathians.•Agricultural expansion before World War ...I, decrease after the collapse of Socialism.•Forest transition during the Interwar period, rapid forest cover increase after 1990.•Deforestation driven by institutions and economies, abandonment by socio-demographics.
Humans have altered land cover for centuries, and land-cover change is a main component of global change. Land use transition trajectories, such as the forest transition theory (i.e. switch from deforestation to stable or increasing forest cover), relate long term changes in land use to gradual changes in underlying drivers, such as economic development, demographic change, and urbanization. However, because only few studies examined land change over centuries, it is not clear how land cover changes during very long time-periods which are punctuated by shifts in socio-economics and policies, such as wars. Our goal here was to examine broad land change patterns and processes, and their main driving forces in Central and Eastern Europe during distinct periods of the past 250 years. We conducted a meta-analysis of 66 publications describing 102 case study locations and quantified the main forest and agricultural changes in the Carpathian region since the 18th century. These studies captured gradual changes since the peak of the Austro-Hungarian Empire up to the accession to the European Union of most of the formerly socialist countries in the study region. Agricultural land-use increased during the Austro-Hungarian Empire in 70% of the case studies, but dropped sharply during and especially after the collapse of the Socialism (over 70% of the cases). The highest rates of abandonment occurred between 1990 and 2000. The Carpathian region experienced forest transition during the Interwar period (93% of the cases), and the forest expansion trend persisted after the collapse of Socialism (70% of the cases). In terms of the drivers, institutional and economic factors were most influential in shaping deforestation and agricultural expansion, while socio-demographics and institutional shifts were the key drivers of land abandonment. Our study highlights the drastic effects that socio-economic and institutional changes can have on land-use and land-cover change, and the value of longitudinal studies of land change to uncover these effects.
Abstract Denaturation of extracellular matrix proteins exposes cryptic binding sites. It is hypothesized that binding of cell adhesion receptors to these cryptic binding sites regulates cellular ...behaviour during tissue repair and regeneration. To test this hypothesis, we quantify the adhesion of pre-osteoblastic cells to native (Col) and partially-denatured (pdCol) collagen I using single-cell force spectroscopy. During early stages of cell attachment (≤180 s) pre-osteoblasts (MC3T3-E1) adhered significantly stronger to pdCol compared to Col. RGD (Arg-Gly-Asp)-containing peptides suppressed this elevated cell adhesion. We show that the RGD-binding α5 β1 - and αv -integrins mediated pre-osteoblast adhesion to pdCol, but not to Col. On pdCol pre-osteoblasts had a higher focal adhesion kinase tyrosine-phosphorylation level that correlated with enhanced spreading and motility. Moreover, pre-osteoblasts cultured on pdCol showed a pronounced matrix mineralization activity. Our data suggest that partially-denatured collagen exposes RGD-motifs that trigger binding of α5 β1 - and αv -integrins. These integrins initiate cellular processes that stimulate osteoblast adhesion, spreading, motility and differentiation. Taken together, these quantitative insights reveal an approach for the development of alternative collagen I- based surfaces for tissue engineering applications.
We present substantial evidence for the existence of a bias in the distribution of births of leading US politicians in favour of those who were the eldest in their cohort at school. This result adds ...to the research on the long-term effects of relative age among peers at school. We discuss parametric and non-parametric tests to identify this effect, and we show that it is not driven by measurement error, redshirting or a sorting effect of highly educated parents. The magnitude of the effect that we estimate is larger than what other studies on 'relative age effects' have found for broader populations but is in general consistent with research that looks at professional sportsmen. We also find that relative age does not seem to correlate with the quality of elected politicians.
Studies of clinical populations that combine MRI data generated at multiple sites are increasingly common. The Canadian Biomarker Integration Network in Depression (CAN-BIND; www.canbind.ca) is a ...national depression research program that includes multimodal neuroimaging collected at several sites across Canada. The purpose of the current paper is to provide detailed information on the imaging protocols used in a number of CAN-BIND studies. The CAN-BIND program implemented a series of platform-specific MRI protocols, including a suite of prescribed structural and functional MRI sequences supported by real-time monitoring for adherence and quality control. The imaging data are retained in an established informatics and databasing platform. Approximately 1300 participants are being recruited, including almost 1000 with depression. These include participants treated with antidepressant medications, transcranial magnetic stimulation, cognitive behavioural therapy and cognitive remediation therapy. Our ability to analyze the large number of imaging variables available may be limited by the sample size of the substudies. The CAN-BIND program includes a multimodal imaging database supported by extensive clinical, demographic, neuropsychological and biological data from people with major depression. It is a resource for Canadian investigators who are interested in understanding whether aspects of neuroimaging — alone or in combination with other variables — can predict the outcomes of various treatment modalities.
We exploit a voting reform in France to estimate the causal effect of exit poll information on turnout and bandwagon voting. Before the change in legislation, individuals in some French overseas ...territories voted after the election result had already been made public via exit poll information from mainland France. We estimate that knowing the exit poll information decreases voter turnout by about 11 percentage points. Our study is the first clean empirical design outside of the laboratory to demonstrate the effect of such knowledge on voter turnout. Furthermore, we find that exit poll information significantly increases bandwagon voting; that is, voters who choose to turn out are more likely to vote for the expected winner.
PDF
