Sensitization Pathways in NIR-Emitting Yb(III) Complexes Bearing 0, +1, +2, or +3 Charges.

Yb(III) complexes of macrocyclic ligands based on 1,4,7,10-tetraazacyclododecane were synthesized. The ligands carried a carbostyril chromophore for Yb(III) sensitization, and carboxylate or carbamide donors for metal binding, forming complexes of 0, +1, +2, or +3 overall charge. The coordination geometry was little affected by the replacement of carboxylates with amides, as shown by paramagnetic 1H NMR spectroscopy. The Yb(III)/Yb(II) reduction potentials were dependent on the nature of the metal binding site, and the more positively charged complexes were easier to reduce. Carbostyril excitation resulted in Yb(III) luminescence in every complex. The residual carbostyril fluorescence quantum yields were smaller in complexes containing more reducible Yb(III) centers decreasing from 5.9% for uncharged complexes to 3.1-4.4% in +3 charged species, suggesting photoinduced electron transfer (PeT) from the antenna to the Yb(III). The relative Yb(III) luminescence quantum yields were identical within the experimental error, except for the +3 charged complex with fully methylated coordinating amides, which was the most intense Yb(III) emitter of the series in water. Quenching of the Yb(III) excited state by NH vibrations proved to limit Yb(III) emission. No clear improvement of the Yb(III) sensitization efficiency was shown upon faster PeT. This result can be explained by the concomitant sensitization of Yb(III) by phonon-assisted energy transfer (PAEnT) from the antenna triplet excited state, which was completely quenched in all of the Yb complexes. Depopulation of the triplet by PeT quenching of the donor singlet excited state would be compensated by the sensitizing nature of the PeT pathway, thus resulting in a constant overall sensitization efficiency across the series.

In Situ Rolling Circle Amplification Förster Resonance Energy Transfer (RCA-FRET) for Washing-Free Real-Time Single-Protein Imaging.

Fluorescence signal enhancement via isothermal nucleic acid amplification is an important approach for sensitive imaging of intra- or extracellular nucleic acid or protein biomarkers. Rolling circle amplification (RCA) is frequently applied for fluorescence in situ imaging but faces limitations concerning multiplexing, dynamic range, and the required multiple washing steps before imaging. Here, we show that Förster resonance energy transfer (FRET) between fluorescent dyes and between lanthanide (Ln) complexes and dyes that hybridize to ß-actin-specific RCA products in HaCaT cells can afford washing-free imaging of single ß-actin proteins. Proximity-dependent FRET could be monitored directly after or during (real-time monitoring) dye or Ln DNA probe incubation and could efficiently distinguish between photoluminescence from ß-actin-specific RCA and DNA probes freely diffusing in solution or nonspecifically attached to cells. Moreover, time-gated FRET imaging with the Ln-dye FRET pairs efficiently suppressed sample autofluorescence and improved the signal-to-background ratio. Our results present an important proof of concept of RCA-FRET imaging with a strong potential to advance in situ RCA toward easier sample preparation, higher-order multiplexing, autofluorescence-free detection, and increased dynamic range by real-time monitoring of in situ RCA.

Screening for the presence of scleroedema adultorum of Buschke in patients with diabetes mellitus: newly diagnosed patients had a high prevalence of dyslipidaemia.

BACKGROUND: Scleroedema adultorum of Buschke is a rare disorder characterized by fibromucinous thickening of the dermis that manifests mainly at the nape of the neck and on the upper back and shoulders. This study screened patients with diabetes mellitus for skin hardening caused by scleroedema adultorum of Buschke and characterized the clinical and laboratory findings in patients with newly identified cases, with a focus on lipid metabolism abnormalities and vascular complications. METHODS: Out of 113 consecutive patients with diabetes, 11 (9.7%) new scleroedema patients, all with type 2 diabetes, were found. Their clinical and laboratory data were compared to those of the rest of the screened patients and to those of a cohort of 15 patients with scleroedema and diabetes who were already being treated in a tertiary clinical centre at the University of Pécs. RESULTS: Higher proportions of patients with dyslipidaemia, hypertriglyceridemia (P < 0.05) and increased mean levels of non-high-density lipoprotein cholesterol (non-HDL-C) were found (P < 0.01) in both scleroedema groups than in the group without scleroedema. Stroke and venous thromboembolism (VTE) were more frequently found in the histories of both the newly identified scleroedema group (each 3/11; 27.3%) and the treated cohort (each 6/15; 40.0%) than in the group without scleroedema (6/102; 5.9% in cases of stroke P = 0.021, P < 0.001; and 14/102; 13.7%; P < 0.05 in cases of VTE, respectively). Based on binary logistic regression, a high non-HDL-C level (odds ratio (OD): 3.338, confidence interval (CI): 1.77-6.28; P < 0.001) and insulin treatment (OR 7.64, CI 1.9-29.3; P = 0.003) were independent predictors of scleroedema in patients with diabetes mellitus. CONCLUSIONS: Diabetes patients with scleroedema had more severe dyslipidaemia and higher occurrence of vascular complications compared to those without scleroedema. In addition to poorly controlled type 2 diabetes mellitus requiring insulin treatment, high non-HDL-C levels may be another contributing factor to the development of scleroedema. TRIAL REGISTRATION: NCT04335396 .

Coordination Environment-Controlled Photoinduced Electron Transfer Quenching in Luminescent Europium Complexes.

The quenching of sensitized Eu(III) luminescence by photoinduced electron transfer from the excited light-harvesting antenna to Eu(III) was investigated. A series of complexes incorporating different metal binding sites and thus having varying Eu(III)/Eu(II) reduction potentials were prepared. The complexes were fully characterized using a combination of single-crystal X-ray crystallography and paramagnetic 1H NMR spectroscopy, the results of which support the structural similarity of the complexes. The redox and photophysical behavior of the Eu(III) center and the light-harvesting antenna were studied using cyclic voltammetry and steady-state and time-resolved emission spectroscopy on the nanosecond and millisecond time scales. The contribution of photoinduced electron transfer to the overall reduction of the Eu(III) luminescence quantum yield was found to be comparable and, in many cases, larger than the quenching caused by well-established processes such as coupling to X-H oscillators. These results suggest that the elimination or mitigation of photoinduced electron transfer could substantially improve the emissive properties of the widely used Eu(III)-based emitters.

Obstructive sleep apnea and hypertriglyceridaemia share common genetic background: Results of a twin study.

Obstructive sleep apnea is associated with an increased risk of hypertension, diabetes and dyslipidaemia. Both obstructive sleep apnea and its comorbidities are at least partly heritable, suggesting a common genetic background. Our aim was to analyse the heritability of the relationship between obstructive sleep apnea and its comorbidities using a twin study. Forty-seven monozygotic and 22 dizygotic adult twin pairs recruited from the Hungarian Twin Registry (mean age 51 ± 15 years) attended an overnight diagnostic sleep study. A medical history was taken, blood pressure was measured, and blood samples were taken for fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and lipoprotein (a). To evaluate the heritability of obstructive sleep apnea and its comorbidities bivariate analysis was performed with an adjustment for age, gender, body mass index (BMI) and smoking after false discovery rate correction and following exclusion of patients on lipid-lowering and antidiabetic medications. There was a significant correlation between indices of obstructive sleep apnea severity, such as the apnea-hypopnea index, oxygen desaturation index and percentage of sleep time spent with oxygen saturation below 90%, as well as blood pressure, serum triglyceride, lipoprotein (a) and glucose levels (all p < .05). The bivariate analysis revealed a common genetic background for the correlations between serum triglyceride and the oxygen desaturation index (r = .63, p = .03), as well as percentage of sleep time spent with oxygen saturation below 90% (r = .58, p = .03). None of the other correlations were significantly genetically or environmentally determined. This twin study demonstrates that the co-occurrence of obstructive sleep apnea with hypertriglyceridaemia has a genetic influence and heritable factors play an important role in the pathogenesis of dyslipidaemia in obstructive sleep apnea.

Eu(III) and Tb(III) Complexes of Octa- and Nonadentate Macrocyclic Ligands Carrying Azide, Alkyne, and Ester Reactive Groups.

Azide- and alkyne-functionalized bioconjugable luminescent lanthanide complexes are reported. Reactive handles were introduced into the complexes by the late-stage modification of a methylenecarboxylic acid antenna pendent group. Tb and Eu quantum yields (11-13% and 3.4-3.6%, respectively) were not greatly affected by the presence of the azide or the alkyne compared to the parent complex (ΦTb = 10%, ΦEu = 2.8%). Two avenues were explored for improving the luminescence of the lanthanide (Ln) complexes: (1) attaching the antenna through a tertiary amide linker and (2) replacing a monodentate carboxylate ligand with a bidentate pyridylcarboxylate donor, which yielded a nonadentate ligand that could saturate the lanthanide coordination sphere and eliminate the quenching metal-bound water molecule that was present in the octadentate complexes. The combination of both approaches yielded Eu and Tb emitters with 5.8% and 46% quantum yields. For the Eu complex, this value was the same as ΦEu in the octadentate parent complex. We attribute this to increased photoinduced electron transfer quenching in the nonadentate species, which compensates for the reduced O-H quenching.

Fast optical method for characterizing plasmonic nanoparticle adhesion on functionalized surfaces.

In this paper, a rapid optical method for characterizing plasmonic (gold) nanoparticle (AuNP) adhesion is presented. Two different methods were used for AuNP preparation: the well-known Turkevich method resulted in particles with negative surface charge; for preparing AuNPs with positive surface charge, stainless steel was used as reducing agent. The solid surface for adhesion was provided by a column packed with pristine or surface-modified glass beads. The size of the nanoparticles was studied by transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS); the surface charge of the components was determined by streaming potential measurements. The characterization of adhesion was performed in a flow system by UV-Vis spectroscopy. During the adhesion experiments, the role of the surface charge, the particle size, and the pH were studied, as well as the adhered amount of gold nanoparticles and the surface coverage values. The latter was estimated by theoretical calculations and defined by the quotient of the measured and the maximal adhered amount of nanoparticles, which could be determined by the cross-sectional area of the NPs and the specific surface area of the glass beads. The results are verified by the polarization reflectometric interference spectroscopy (PRIfS) method: silica nanoparticles with diameters of a few hundred (d~450) nanometers were immobilized on the surface of glass substrate by the Langmuir-Blodgett method, the surface was modified similar to the 3D (continuous flow packed column) system, and gold nanoparticles from different pH solutions were adhered during the measurements. These kinds of modified surfaces allow the investigation of biomolecule adsorption in the same reflectometric setup. Graphical abstract.

The human ABCB6 protein is the functional homologue of HMT-1 proteins mediating cadmium detoxification.

ABCB6 belongs to the family of ATP-binding cassette (ABC) transporters, which transport various molecules across extra- and intra-cellular membranes, bearing significant impact on human disease and pharmacology. Although mutations in the ABCB6 gene have been linked to a variety of pathophysiological conditions ranging from transfusion incompatibility to pigmentation defects, its precise cellular localization and function is not understood. In particular, the intracellular localization of ABCB6 has been a matter of debate, with conflicting reports suggesting mitochondrial or endolysosomal expression. ABCB6 shows significant sequence identity to HMT-1 (heavy metal tolerance factor 1) proteins, whose evolutionarily conserved role is to confer tolerance to heavy metals through the intracellular sequestration of metal complexes. Here, we show that the cadmium-sensitive phenotype of Schizosaccharomyces pombe and Caenorhabditis elegans strains defective for HMT-1 is rescued by the human ABCB6 protein. Overexpression of ABCB6 conferred tolerance to cadmium and As(III) (As2O3), but not to As(V) (Na2HAsO4), Sb(V), Hg(II), or Zn(II). Inactivating mutations of ABCB6 abolished vacuolar sequestration of cadmium, effectively suppressing the cadmium tolerance phenotype. Modulation of ABCB6 expression levels in human glioblastoma cells resulted in a concomitant change in cadmium sensitivity. Our findings reveal ABCB6 as a functional homologue of the HMT-1 proteins, linking endolysosomal ABCB6 to the highly conserved mechanism of intracellular cadmium detoxification.

Lanthanide(III) Complexes of Cyclen Triacetates and Triamides Bearing Tertiary Amide-Linked Antennae.

The coordination compounds of the trivalent lanthanide ions (Ln(III)) have unique photophysical properties. Ln(III) excitation is usually performed through a light-harvesting antenna. To enable Ln(III)-based emitters to reach their full potential, an understanding of how complex structure affects sensitization and quenching processes is necessary. Here, the role of the linker between the antenna and the metal binding fragment was studied. Four macrocyclic ligands carrying coumarin 2 or 4-methoxymethylcarbostyril sensitizing antennae linked to an octadentate macrocyclic ligand binding site were synthesized. Complexation with Ln(III) (Ln = La, Sm, Eu, Gd, Tb, Yb and Lu) yielded species with overall -1, 0, or +2 and +3-charge. Paramagnetic 1H NMR spectroscopy indicated subtle differences between the coumarin- and carbostyril-carrying Eu(III) and Yb(III) complexes. Cyclic voltammetry showed that the effect of the linker on the Eu(III)/Eu(II) apparent reduction potential was dependent on the electronic properties of the N-substituent. The Eu(III), Tb(III) and Sm(III) complexes were all luminescent. Coumarin-sensitized complexes were poorly emissive; photoinduced electron transfer was not a major quenching pathway in these species. These results show that seemingly similar emitters can undergo very different photophysical processes, and highlight the crucial role the linker can play.

Genetic influences on the onset of obstructive sleep apnoea and daytime sleepiness: a twin study.

BACKGROUND: Obstructive sleep apnoea (OSA) is one of the major sources of the excessive daily sleepiness, cognitive dysfunction, and it increases cardiovascular morbidity and mortality. Previous studies suggested a possible genetic influence, based on questionnaires but no objective genetic study was conducted to understand the exact variance underpinned by genetic factors. METHODS: Seventy-one Hungarian twin pairs involved from the Hungarian Twin Registry (48 monozygotic, MZ and 23 dizygotic, DZ pairs, mean age 51 ± 15 years) underwent overnight polysomnography (Somnoscreen Plus Tele PSG, Somnomedics GMBH, Germany). Apnoea hypopnea index (AHI), respiratory disturbance index (RDI) and oxygen desaturation index (ODI) were registered. Daytime sleepiness was measured with the Epworth Sleepiness Scale (ESS). Bivariate heritability analysis was applied. RESULTS: The prevalence of OSA was 41% in our study population. The heritability of the AHI, ODI and RDI ranged between 69% and 83%, while the OSA, defined by an AHI ≥5/h, was itself 73% heritable. The unshared environmental component explained the rest of the variance between 17% and 31%. Daytime sleepiness was mostly determined by the environment, and the variance was influenced in 34% by the additive genetic factors. These associations were present after additional adjustment for body mass index. CONCLUSION: OSA and the indices of OSA severity are heritable, while daytime sleepiness is mostly influenced by environmental factors. Further studies should elucidate whether close relatives of patients with OSA may benefit from early family risk based screening.

Comprehensive coronary plaque assessment in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease. Previous studies have assessed the relationship between OSA and coronary artery disease (CAD) using coronary artery calcium score (CAC) measurements. However, limited data are available regarding the association of OSA with non-calcified plaque burden. We therefore aimed to assess the relationship between CAD severity as assessed by coronary computed tomography angiography (CTA) and OSA. Forty-one adult subjects (59 ± 9 years, 15 men) underwent a 256-slice coronary CTA, which was followed by a diagnostic attended cardiorespiratory polygraphy (n = 13) or polysomnography (n = 28). Segment involvement score (SIS), segment stenosis score (SSS) and CAC were used to quantify total CAD burden. Correlation analysis was used to assess potential associations between CAD and OSA. Twenty-two patients were diagnosed with OSA. SIS and SSS were elevated in OSA (2.90 ± 2.78 versus 1.79 ± 2.39 and 4.91 ± 5.94 versus 1.79 ± 4.54, OSA versus controls, SIS and SSS respectively, both p < 0.01) and correlated with OSA severity as measured by the apnea-hypopnea index (AHI, r = 0.41 and 0.43, p < 0.01) and oxygen desaturation index (ODI, r = 0.45 and 0.46, p < 0.01). However, no significant correlation was observed between CAC and OSA. Compared to CAC, SIS and SSS provide additional information on coronary plaque burden in OSA, which shows a significant association with OSA.

HSF1Base: A Comprehensive Database of HSF1 (Heat Shock Factor 1) Target Genes.

HSF1 (heat shock factor 1) is an evolutionarily conserved master transcriptional regulator of the heat shock response (HSR) in eukaryotic cells. In response to high temperatures, HSF1 upregulates genes encoding molecular chaperones, also called heat shock proteins, which assist the refolding or degradation of damaged intracellular proteins. Accumulating evidence reveals however that HSF1 participates in several other physiological and pathological processes such as differentiation, immune response, and multidrug resistance, as well as in ageing, neurodegenerative demise, and cancer. To address how HSF1 controls these processes one should systematically analyze its target genes. Here we present a novel database called HSF1Base (hsf1base.org) that contains a nearly comprehensive list of HSF1 target genes identified so far. The list was obtained by manually curating publications on individual HSF1 targets and analyzing relevant high throughput transcriptomic and chromatin immunoprecipitation data derived from the literature and the Yeastract database. To support the biological relevance of HSF1 targets identified by high throughput methods, we performed an enrichment analysis of (potential) HSF1 targets across different tissues/cell types and organisms. We found that general HSF1 functions (targets are expressed in all tissues/cell types) are mostly related to cellular proteostasis. Furthermore, HSF1 targets that are conserved across various animal taxa operate mostly in cellular stress pathways (e.g., autophagy), chromatin remodeling, ribosome biogenesis, and ageing. Together, these data highlight diverse roles for HSF1, expanding far beyond the HSR.

Are the Variants of the Circle of Willis Determined by Genetic or Environmental Factors? Results of a Twin Study and Review of the Literature.

BACKGROUND: Anatomic variants of the circle of Willis (CW) are commonly observed in healthy subjects. Genetic and environmental factors influencing these variants remain unclear. Our aim was to assess the genetic and environmental background affecting variant CW phenotypes. METHODS: A total of 122 adult healthy twins from the Hungarian Twin Registry (39 monozygotic (MZ) and 22 dizygotic (DZ) pairs, average age 49.7 ± 13.4 years) underwent Time-of-Flight magnetic resonance angiography and transcranial Doppler sonography. We investigated the anterior and posterior CW according to morphological categories. Prevalence and concordance rates of CW variants were calculated. MZ twins discordant for CW variants were analyzed for cardiovascular risk factors and altered blood flow. RESULTS: Complete CW (45.0%) and bilaterally absent posterior communicating artery (PCoA) (22.5%) were the most prevalent variants in the anterior and posterior CW, respectively. There was no significant difference regarding the prevalence of variants across zygosity except for bilaterally hypoplastic PCoA (p = .02). DZ concordance was higher compared to MZ twins regarding morphological categories of the CW. Cardiovascular risk factors were not significantly associated with variant CW in MZ twins discordant to CW morphology. Flow parameters did not differ significantly among MZ twins discordant to CW variants. CONCLUSION: CW variants may not be determined by substantial genetic effects and are not influenced by altered blood flow in healthy individuals. Further investigations are needed to identify potential environmental factors affecting these variants.

Photophysics of Coumarin and Carbostyril-Sensitized Luminescent Lanthanide Complexes: Implications for Complex Design in Multiplex Detection.

Luminescent lanthanide (Ln(III)) complexes with coumarin or carbostyril antennae were synthesized and their photophysical properties evaluated using steady-state and time-resolved UV-vis spectroscopy. Ligands bearing distant hydroxycoumarin-derived antennae attached through triazole linkers were modest sensitizers for Eu(III) and Tb(III), whereas ligands with 7-amidocarbostyrils directly linked to the coordination site could reach good quantum yields for multiple Ln(III), including the visible emitters Sm(III) and Dy(III), and the near-infrared emitters Nd(III) and Yb(III). The highest lanthanide-centered luminescence quantum yields were 35% (Tb), 7.9% (Eu), 0.67% (Dy), and 0.18% (Sm). Antennae providing similar luminescence intensities with 2-4 Ln-emitters were identified. Photoredox quenching of the carbostyril antenna excited states was observed for all Eu(III)-complexes and should be sensitizing in the case of Yb(III); the scope of the process extends to Ln(III) for which it has not been seen previously, specifically Dy(III) and Sm(III). The proposed process is supported by photophysical and electrochemical data. A FRET-type mechanism was identified in architectures with both distant and close antennae for all of the Lns. This mechanism seems to be the only sensitizing one at long distance and probably contributes to the sensitization at shorter distances along with the triplet pathway. The complexes were nontoxic to either bacterial or mammalian cells. Complexes of an ester-functionalized ligand were taken up by bacteria in a concentration-dependent manner. Our results suggest that the effects of FRET and photoredox quenching should be taken into consideration when designing luminescent Ln complexes. These results also establish these Ln(III)-complexes for multiplex detection beyond the available two-color systems.

Overnight Changes in Lung Function of Obese Patients with Obstructive Sleep Apnoea.

PURPOSE: Obstructive sleep apnoea (OSA) is a prevalent disorder, characterised by collapse of the upper airways during sleep. The impact of sleep-disordered breathing on pulmonary function indices is however currently not well described. The aim of the study was to evaluate diurnal change in lung function indices in a cohort of patients with OSA and relate pulmonary function changes to disease severity. METHODS: 42 patients with OSA and 73 healthy control subjects participated in the study. Asthma and COPD were excluded in all volunteers following a clinical and spirometric assessment. Spirometry was then performed in all subjects in the evening and the morning following a polysomnography study. RESULTS: There was no difference in evening or morning FEV1 or FVC between patients and control subjects (p > 0.05). Neither FEV1 nor FVC changed in control subjects overnight (p > 0.05). In contrast, FEV1 significantly increased from evening (2.18/1.54-4.46/L) to morning measurement (2.26/1.42-4.63/L) in OSA without any change in FVC. The FEV1 increase in OSA was related to male gender, obesity and the lack of treatment with statins or ß-blockers (all p < 0.05). A tendency for a direct correlation was apparent between overnight FEV1 change and RDI (p = 0.05, r = 0.30). CONCLUSIONS: Diurnal variations in spirometric indices occur in patients with OSA and FEV1 appears to increase in subjects with OSA overnight. These changes occur in the absence of change in FVC and are directly related to the severity of OSA. These findings dictate a need to consider time of lung function measurement.

Age-dependent heat shock hormesis to HSF-1 deficiency suggests a compensatory mechanism mediated by the unfolded protein response and innate immunity in young Caenorhabditis elegans.

The transcription factor HSF-1 (heat shock factor 1) acts as a master regulator of heat shock response in eukaryotic cells to maintain cellular proteostasis. The protein has a protective role in preventing cells from undergoing ageing, and neurodegeneration, and also mediates tumorigenesis. Thus, modulating HSF-1 activity in humans has a promising therapeutic potential for treating these pathologies. Loss of HSF-1 function is usually associated with impaired stress tolerance. Contrary to this conventional knowledge, we show here that inactivation of HSF-1 in the nematode Caenorhabditis elegans results in increased thermotolerance at young adult stages, whereas HSF-1 deficiency in animals passing early adult stages indeed leads to decreased thermotolerance, as compared to wild-type. Furthermore, a gene expression analysis supports that in young adults, distinct cellular stress response and immunity-related signaling pathways become induced upon HSF-1 deficiency. We also demonstrate that increased tolerance to proteotoxic stress in HSF-1-depleted young worms requires the activity of the unfolded protein response of the endoplasmic reticulum and the SKN-1/Nrf2-mediated oxidative stress response pathway, as well as an innate immunity-related pathway, suggesting a mutual compensatory interaction between HSF-1 and these conserved stress response systems. A similar compensatory molecular network is likely to also operate in higher animal taxa, raising the possibility of an unexpected outcome when HSF-1 activity is manipulated in humans.

The influence of random-coil chemical shifts on the assessment of structural propensities in folded proteins and IDPs.

In studying secondary structural propensities of proteins by nuclear magnetic resonance (NMR) spectroscopy, secondary chemical shifts (SCSs) serve as the primary atomic scale observables. For SCS calculation, the selection of an appropriate random coil chemical shift (RCCS) dataset is a crucial step, especially when investigating intrinsically disordered proteins (IDPs). The scientific literature is abundant in such datasets, however, the effect of choosing one over all the others in a concrete application has not yet been studied thoroughly and systematically. Hereby, we review the available RCCS prediction methods and to compare them, we conduct statistical inference by means of the nonparametric sum of ranking differences and comparison of ranks to random numbers (SRD-CRRN) method. We try to find the RCCS predictors best representing the general consensus regarding secondary structural propensities. The existence and the magnitude of resulting differences on secondary structure determination under varying sample conditions (temperature, pH) are demonstrated and discussed for globular proteins and especially IDPs.

Flood risk management: U.S. Army Corps of Engineers and layperson perceptions.

Recent severe storm experiences in the U.S. Gulf Coast illustrate the importance of an integrated approach to flood preparedness planning that harmonizes stakeholder and agency efforts. Risk management decisions that are informed by and address decision maker and stakeholder risk perceptions and behavior are essential for effective risk management policy. A literature review and two expert models/mental models studies were undertaken to identify areas of importance in the flood risk management process for layperson, non-USACE-expert, and two USACE-expert groups. In characterizing and mapping stakeholder beliefs about risks in the literature onto current risk management practice, recommendations for accommodating and changing stakeholder perceptions of flood risks and their management are identified. Needs of the U.S. Army Corps of Engineers (USACE) flood preparedness and response program are discussed in the context of flood risk mental models.

Functional diversification of heat shock factors.

Heat shock transcription factors (HSFs) are widely known as master regulators of the heat shock response. In invertebrates, a single heat shock factor, HSF1, is responsible for the maintenance of protein homeostasis. In vertebrates, seven members of the HSF family have been identified, namely HSF1, HSF2, HSF3, HSF4, HSF5, HSFX, and HSFY, of which HSF1 and HSF2 are clearly associated with heat shock response, while HSF4 is involved in development. Other members of the family have not yet been studied as extensively. Besides their role in cellular proteostasis, HSFs influence a plethora of biological processes such as aging, development, cell proliferation, and cell differentiation, and they are implicated in several pathologies such as neurodegeneration and cancer. This is achieved by regulating the expression of a great variety of genes including chaperones. Here, we review our current knowledge on the function of HSF family members and important aspects that made possible the functional diversification of HSFs.

The Relevance of Goodness-of-fit, Robustness and Prediction Validation Categories of OECD-QSAR Principles with Respect to Sample Size and Model Type.

We investigated the relevance of the validation principles on the Quantitative Structure Activity Relationship models issued by Organization for Economic and Co-operation and Development. We checked the goodness-of-fit, robustness and predictivity categories in linear and nonlinear models using benchmark datasets. Most of our conclusions are drawn using the sample size dependence of the different validation parameters. We found that the goodness-of-fit parameters misleadingly overestimate the models on small samples. In the case of neural network and support vector models, the feasibility of the goodness-of-fit parameters often might be questioned. We propose to use the simplest y-scrambling method to estimate chance correlation. We found that the leave-one-out and leave-many-out cross-validation parameters can be rescaled to each other in all models and the computationally feasible method should be chosen depending on the model type. We assessed the interdependence of the validation parameters by calculating their rank correlations. Goodness of fit and robustness correlate quite well over a sample size for linear models and one of the approaches might be redundant. In the rank correlation between internal and external validation parameters, we found that the assignment of good and bad modellable data to the training or the test causes negative correlations.