Decoupling a tandem-repeat protein: Impact of multiple loop insertions on a modular scaffold

Abstract: The simple topology and modular architecture of tandem-repeat proteins such as tetratricopeptide repeats (TPRs) and ankyrin repeats makes them straightforward to dissect and redesign. Repeat-protein stability can be manipulated in a predictable way using site-specific mutations. Here we explore a different type of modification - loop insertion - that will enable a simple route to functionalisation of this versatile scaffold. We previously showed that a single loop insertion has a dramatically different effect on stability depending on its location in the repeat array. Here we dissect this effect by a combination of multiple and alternated loop insertions to understand the origins of the context-dependent loss in stability. We find that the scaffold is remarkably robust in that its overall structure is maintained. However, adjacent repeats are now only weakly coupled, and consequently the increase in solvent protection, and thus stability, with increasing repeat number that defines the tandem-repeat protein class is lost. Our results also provide us with a rulebook with which we can apply these principles to the design of artificial repeat proteins with precisely tuned folding landscapes and functional capabilities, thereby paving the way for their exploitation as a versatile and truly modular platform in synthetic biology

depressive spectrum disorders in cancer prevalence risk factors and screening for depression a critical review

AbstractBackground: Although depression and mood-related disorders are common in persons with cancer, these conditions remain frequently overlooked in clinical practice. Negative consequences of depressive disorder spectrum have been reported (e.g. suicidal ideation, increase physical complications and somatic symptoms, negative influence on prognosis), indicating the need for routine screening, assessment and management.Methods: A search of the major databases (Medline, Embase, PsycLIT, PsycINFO, and the Cochrane Library) was conducted on the reviews and meta-analyses available in order to summarize relevant data concerning depressive disorders spectrum in terms of prevalence, risk factors, and screening and assessment among patients with cancer across the trajectory of the disease.Results: The data show a prevalence of depression and depressive disorders between 5% and 60% according to the different diagnostic criteria, the tools used in the studies (e.g. semi-structured psychiatric interview and psycho..

Raman microprobe observation of intercalate contraction in graphite intercalation compounds

Raman microprobe spectra of SbCl5, Br2, and FeCl3 graphite intercalation compounds have been obtained with a spatial resolution of 2 m. Depletion of the intercalate was observed within 10 m of the sample edge in the SbCl5-graphite samples, and this observation is found to be consistent with a model in which the intercalate contracts thermally as the sample is cooled after the intercalation reaction is completed. No depletion was observed in the Br2 and FeCl3 graphite intercalation compounds, consistent with the low intercalation temperature of the former and the small thermal expansion coefficient of the latter

CCAFS midline synthesis – Ghana. Assessment of changes at household, village and organization levels since the 2011 CCAFS baseline surveys

The objective of the CCAFS midline surveys was to assess what kinds of changes have occurred and whether these changes are helping the households and villages adapt to and mitigate climate change. It also provided information at the village level about some basic indicators of natural resource utilization, organizational landscapes, information networks for weather and agricultural information, as well as mitigation baseline information, which can be compared across sites and monitored over time. The same tools were used with a few improvements to ensure comparability with the data collected in 2011. This info note provides a synthesis of the changes at the household, village and organizational levels emphasizing major indicators that have changed

Anxiety and depression in adult cancer patients: ESMO Clinical Practice Guideline

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Genome-Wide Analysis of the Effects of Heat Shock on a Saccharomyces cerevisiae Mutant With a Constitutively Activated cAMP-Dependent Pathway

We have used DNA microarray technology and 2-D gel electrophoresis combined with mass spectrometry to investigate the effects of a drastic heat shock from 30℃ to 50℃ on a genome-wide scale. This experimental condition is used to differentiate between wild-type cells and those with a constitutively active cAMP-dependent pathway in Saccharomyces cerevisiae. Whilst more than 50% of the former survive this shock, almost all of the latter lose viability. We compared the transcriptomes of the wildtype and a mutant strain deleted for the gene PDE2, encoding the high-affinity cAMP phosphodiesterase before and after heat shock treatment. We also compared the two heat-shocked samples with one another, allowing us to determine the changes that occur in the pde2Δ mutant which cause such a dramatic loss of viability after heat shock. Several genes involved in ergosterol biosynthesis and carbon source utilization had altered expression levels, suggesting that these processes might be potential factors in heat shock survival. These predictions and also the effect of the different phases of the cell cycle were confirmed by biochemical and phenotypic analyses. 146 genes of previously unknown function were identified amongst the genes with altered expression levels and deletion mutants in 13 of these genes were found to be highly sensitive to heat shock. Differences in response to heat shock were also observed at the level of the proteome, with a higher level of protein degradation in the mutant, as revealed by comparing 2-D gels of wild-type and mutant heat-shocked samples and mass spectrometry analysis of the differentially produced proteins

Beyond words: Aesthetic knowledge and knowing in design

Aesthetic knowledge comes from practitioners understanding the look, feel, smell, taste and sound of things. It is vital to work in many organizational contexts. In this paper, we explore aesthetic knowledge and knowing in organizations through detailed observation of design work in the architectural practice Edward Cullinan Architects. Through our research, we explore aesthetic knowledge in the context of architectural work, we unpack what it is, how it is generated, and how it is applied in design projects, shared between practitioners and developed at the level of the organization. Our analysis suggests that aesthetic knowledge plays an important part in organizational practice, not only as the symbolic context for work, but as an integral part of the work that people do. It suggests that aesthetic reflexivity, which involves an opening up and questioning of what is known, is experienced as part of practice as well as a `time out' from practice