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Motor–cognitive training in Parkinson’s disease (PD) can positively affect gait and balance, but whether motor–cognitive (dual-task) performance improves is unknown. This meta-analysis, therefore, aimed to establish the current evidence on the effects of motor–cognitive training on dual-task performance in PD. Systematic searches were conducted in five databases and 11 studies with a total of 597 people (mean age: 68.9 years; mean PD duration: 6.8 years) were included. We found a mean difference in dual-task gait speed (0.12 m/s (95% CI 0.08, 0.17)), dual-task cadence (2.91 steps/min (95% CI 0.08, 5.73)), dual-task stride length (10.12 cm (95% CI 4.86, 15.38)) and dual-task cost on gait speed (− 8.75% (95% CI − 14.57, − 2.92)) in favor of motor–cognitive training compared to controls. The GRADE analysis revealed that the findings were based on high certainty evidence. Thus, we can for the first time systematically show that people with PD can improve their dual-task ability through motor–cognitive training.

Objective: To determine the effects of low- vs. high-intensity aerobic and resistance training on motor and cognitive function, brain activation, brain structure, and neurochemical markers of neuroplasticity and the association thereof in healthy young and older adults and in patients with multiple sclerosis, Parkinson's disease, and stroke. Design: Systematic review and robust variance estimation meta-analysis with meta-regression. Data sources: Systematic search of MEDLINE, Web of Science, and CINAHL databases. Results: Fifty studies with 60 intervention arms and 2283 in-analyses participants were included. Due to the low number of studies, the three patient groups were combined and analyzed as a single group. Overall, low- (g=0.19, p = 0.024) and high-intensity exercise (g=0.40, p = 0.001) improved neuroplasticity. Exercise intensity scaled with neuroplasticity only in healthy young adults but not in healthy older adults or patient groups. Exercise-induced improvements in neuroplasticity were associated with changes in motor but not cognitive outcomes. Conclusion: Exercise intensity is an important variable to dose and individualize the exercise stimulus for healthy young individuals but not necessarily for healthy older adults and neurological patients. This conclusion warrants caution because studies are needed that directly compare the effects of low- vs. high-intensity exercise on neuroplasticity to determine if such changes are mechanistically and incrementally linked to improved cognition and motor function.

Background. Recent studies indicate that exercise can induce neuroplastic changes in people with Parkinson’s disease (PwPD). Reports of feasibility outcomes from existing pilot trials however are, of date, insufficient to enable replication by others in larger definitive trials. Objective. To evaluate trial design for a definitive trial by exploring process and scientific feasibility. Methods. The trial design was a parallel-group RCT pilot with a 1 : 1 allocation ratio to either HiBalance or an active control group (HiCommunication). Both groups received one-hour sessions twice weekly, plus home exercises weekly, for 10 weeks. Participants with mild-to-moderate Parkinson’s disease (PD) were recruited via advertisement. Assessment included physical performance, structural and functional MRI, blood sampling, neuropsychological assessment, and speech/voice assessment. Process and scientific feasibility were monitored throughout the study. Process feasibility involved recruitment, participant acceptability of assessments and interventions, assessment procedures (focus on imaging, blood sampling, and dual-task gait analysis), and blinding procedures. Scientific feasibility involved trends in outcome response and safety during group training and home exercises. Data are presented in median, minimum, and maximum values. Changes from pre- to postintervention are reported descriptively. Results. Thirteen participants were included (4 women, mean age 69.7 years), with a recruitment rate of 31%. Attendance rates and follow-up questionnaires indicated that both groups were acceptable to participate. Image quality was acceptable; however, diplopia and/or sleepiness were observed in several participants during MRI. With regard to dual-task gait performance, there appeared to be a ceiling effect of the cognitive tasks with seven participants scoring all correct answers at pretest. Blinding of group allocation was successful for one assessor but was broken for half of participants for the other. Conclusions. The overall trial design proved feasible to perform, but further strengthening ahead of the definitive RCT is recommended, specifically with respect to MRI setup, cognitive dual-tasks during gait, and blinding procedures. This trial is registered with NCT03213873.

Quick responses to a loss of balance or "automatic postural responses" (APRs) are critical for fall prevention. The addition of a distracting task- dual-tasking (DT), typically worsens performance on mobility tasks. However, the effect of DT on APRs is unclear. We conducted a systematic review and meta-analyses to examine the effects of DT on spatial, temporal, and neuromuscular components of APRs and the effect of DT on cognitive performance. A Meta-analysis of 19 cohorts (n = 329) showed significant worsening in spatial kinematic features of APRs under DT conditions (P = 0.01), and a meta-analysis of 9 cohorts (n = 123) demonstrated later muscle onset during DT (P = 0.003). No significant DT effect was observed for temporal kinematic outcomes in 18 cohorts (n = 328; P = 0.47). Finally, significant declines in cognitive performance were evident in 20 cohorts (n = 400; P = 0.002). These results indicate that, despite the somewhat reactive nature of APRs, the addition of a secondary task negatively impacts some aspects of the response. These findings underscore the importance of cortical structures in APR generation. Given the importance of APRs for falls, identifying aspects of APRs that are altered under DT may inform fall-prevention treatment approaches.

Background Parkinson’s disease (PD) is a devastating neurodegenerative disorder. Reduced balance is one of the cardinal symptoms of PD, predisposing people living with PD to experience difficulties with the execution of tasks and activities, as well as hindering their involvement in meaningful life areas. The overarching aim of this study was to explore how deficits in balance control manifest in everyday life and how it is managed by people with PD (PwPD). Methods Qualitative description was used as methodology, and in-depth interviews were conducted with 18 participants, between the ages of 46 to 83 years, with mild to severe PD. Interview transcripts were analyzed using qualitative content analysis, following an inductive approach. Results One theme emerged from the analysis: Increased planning—choreographing life. Within this overarching theme, two categories were identified, namely Limitations in mobility and New restricted functioning in everyday life, each with 3–4 sub-categories. The categories described how PwPD handled decreased balance control in their everyday life by using motor and cognitive strategies as a consequence of not trusting their body’s capacity to control balance. Activities in everyday life, as well as the ability to partake in leisure and social activities were profoundly affected. Conclusion People with mild to severe PD used strategies to handle decreased balance and they choreographed their lives around their individual current state of mobility and balance. The knowledge gained from this study can be used to develop targeted interventions addressing the nuances of balance deficits in everyday life.

BACKGROUND: Eosinophilic esophagitis (EoE) is an esophageal inflammatory disease associated with atopic diseases. Thymic stromal lymphopoietin (TSLP) and calpain 14 (CAPN14) genetic variations contribute to EoE, but how this relates to atopy is unclear. OBJECTIVE: The purpose of this study was to explore the relationship between EoE, atopy, and genetic risk. METHODS: EoE-atopy enrichment was tested by using 700 patients with EoE and 801 community control subjects. Probing 372 single nucleotide polymorphisms (SNPs) in 63 atopy genes, we evaluated EoE associations using 412 nonatopic and 868 atopic disease control subjects. Interaction and stratified analyses of EoE-specific and atopy-related SNPs were performed. RESULTS: Atopic disease was enriched in patients with EoE (P < .0001). Comparing patients with EoE and nonatopic control subjects, EoE associated strongly with IL-4/kinesin family member 3A (IL4/KIF3A) (P = 2.8 × 10(−6); odds ratio [OR], 1.87), moderately with TSLP (P = 1.5 × 10(−4); OR, 1.43), and nominally with CAPN14 (P = .029; OR, 1.35). Comparing patients with EoE with atopic disease control subjects, EoE associated strongly with ST2 (P = 3.5 × 10(−6); OR, 1.77) and nominally with IL4/KIF3A (P = .019; OR, 1.25); TSLP’s association persisted (P = 4.7 × 10(−5); OR, 1.37), and CAPN14’s association strengthened (P = .0001; OR, 1.71). Notably, there was gene-gene interaction between TSLP and IL4 SNPs (P = .0074). Children with risk alleles for both genes were at higher risk for EoE (P = 2.0 × 10(−10); OR, 3.67). CONCLUSIONS: EoE genetic susceptibility is mediated by EoE-specific and general atopic disease loci, which can have synergistic effects. These results might aid in identifying potential therapeutics and predicting EoE susceptibility.

BACKGROUND AND PURPOSE: In order for people with Parkinson disease (PwPD) to benefit from neurorehabilitation research, interventions tested in research settings require assessment in real-world clinical practice. There is little evidence for whether efficacious exercise interventions for PwPD remain effective when transferred to standard clinical settings. The aim of this study was to assess the clinical effectiveness of the adapted HiBalance program on balance control and gait among PwPD. METHODS: Participants (n = 117) with mild-moderate Parkinson disease were consecutively included into either the 10-week HiBalance group training (n = 61) or the control (n = 56) group. The main outcome was balance performance (Mini-BESTest). Secondary outcomes were comfortable gait speed (10-m Walk Test); functional mobility (Timed Up and Go [TUG] test) and dual-task interference (cognitive TUG test); physical activity level (steps per day); perceived balance confidence (Activities-specific Balance Confidence scale) and perceived walking difficulty (Walk-12G) and self-rated health (EQ-5D visual analog scale). RESULTS: In total, 98 people completed the trial. Compared with controls, the training group showed significant improvement in balance performance (P < 0.001), gait speed (P = 0.001), and dual-task interference (P = 0.04) following the intervention. No group differences were observed for physical activity level or any patient-reported measures. DISCUSSION AND CONCLUSIONS: Highly challenging balance training is effective at improving balance, gait, and dual-task performance when delivered at a clinically feasible dose, in a range of rehabilitation settings, without direct involvement of the research group.Video Abstract available for more insights from the authors (see the Video, Supplementary Digital Content 1, available at: http://links.lww.com/JNPT/A299).

Background Parkinson’s disease (PD) affects many physiological systems essential for balance control. Recent studies suggest that intensive and cognitively demanding physical exercise programs are capable of inducing plastic brain changes in PD. We have developed a highly challenging balance training (the HiBalance) program that emphasizes critical aspects of balance control through progressively introducing more challenging exercises which incorporates dual-tasking. Earlier studies have shown it to be effective in improving balance, gait and dual-tasking. The study design has thereafter been adjusted to link intervention-induced behavioral changes to brain morphology and function. Specifically, in this randomized controlled trial, we will determine the effects of the HiBalance program on balance, gait and cognition and relate this to task-evoked functional MRI (fMRI), as well as brain-derived neurotrophic factor (BDNF) in participants with mild-moderate PD. Methods One hundred participants with idiopathic PD, Hoehn & Yahr stage 2 or 3, ≥ 60 years of age, ≥ 21 on Montreal Cognitive Assessment will be recruited in successive waves and randomized into either the HiBalance program or to an active control group (the HiCommunication program, targeting speech and communication). Both interventions will be performed in small groups, twice a week with 1 h sessions for 10 weeks. In addition, a 1 h, once a week, home exercise program will also be performed. A double-blinded design will be used. At the pre- and post-assessments, participants will be assessed on balance (main outcome), gait, cognitive functions, physical activity, voice/speech function, BDNF in serum and fMRI (3 T Philips) during performance of motor-cognitive tasks. Discussion Since there is currently no cure for PD, findings of neuroplastic brain changes in response to exercise would revolutionize the way we treat PD, and, in turn, provide new hope to patients for a life with better health, greater independence and improved quality of life. Trial registration ClincalTrials.gov: NCT03213873, first posted July 11, 2017.

Exposure to air pollution is associated with enhanced risk of developing asthma, notably in the presence of genetic risk factors. Interaction analyses have shown that both outdoor and indoor air pollution interact with genetic variability to increase the incidence of asthma. In this review, we summarize recent progress in candidate gene-based studies, as well as genome-wide gene-air pollution interaction studies. Advances in epigenetics have provided evidence for DNA methylation as a mediator in gene-air pollution interactions. Emerging strategies for study design and statistical analyses may improve power in future studies. Improved air pollution exposure assessment methods and asthma endo-typing can also be expected to increase the ability to detect biologically driven gene-air pollution interaction effects.

Shortened time-to-market cycles and increasingly complex systems are just some of the challenges faced by industry. The requirement engineering process needs to adapt to these challenges in order to guarantee that the end product fulfils the customer expectations as well as the necessary safety norms. The goal of this paper is to investigate the way engineers work in practice with the requirement engeneering processes at different stages of the development, with a particular focus on the use of requirements in cross domain development and to compare this to the existing theory in the domain.

This paper contributes to a TEM examination on the oxide films formed at three locations along a crack path in Alloy 182 weld from a BWR core shroud support leg, namely, the crack mouth, the midway between the mouth and the crack tip, and the crack tip. In the crack mouth the oxide film was approximately 1.6 μm in thickness and consisted of relatively pure NiO. The midway oxide film was mainly a nickel chromium oxide with a film thickness of 0.3 μm. At the crack tip the oxide film was a nickel chromium iron oxide with a film thickness of 30 nm. In all studied locations the main oxides had the similar rocksalt structure and the cracks were much wider than the thicknesses of the oxide films. It probably suggests that the corroded metal was largely dissolved into the coolant. The different dissolution rates of nickel, chromium and iron cations in the oxide films are clearly displayed with the compositions of the residual oxides. The oxide stability under different redox potentials along the crack path is briefly discussed.

How forward and backward walking, both central to everyday life, relate to cognition are relatively unexplored in people with dementia. This study aimed to investigate if forward and backward walking velocity respectively, associated with global cognition and executive function in people with dementia, and whether the association differed according to walking aid use or dementia type. Using a cross-sectional design, 161 participants (77% women), a mean Mini-Mental State Examination (MMSE) score of 15, and mean age of 85.5years and living in nursing homes were included. Self-paced forward walking (FW) and backward walking (BW) velocity over 2.4m was measured. Global cognitive outcome measurements included MMSE and Alzheimer Disease Assessment Scale - Cognitive subscale (ADAS-Cog). Executive function was measured using Verbal Fluency (VF). In comprehensively adjusted multivariate linear regression analyses, FW was independently associated with VF (p=0.001), but not MMSE (p=0.126) or ADAS-Cog (p=0.818). BW was independently associated with VF (p=0.043) and MMSE (p=0.022), but not ADAS-Cog (p=0.519). Interaction analyses showed that the association between BW velocity and executive function were stronger in participants who walked without a walking aid. No associations differed according to dementia type. In conclusion, executive function appears important to walking velocity, both forward and backward, in people with dementia with mild to moderately severe cognitive impairment. Global cognitive function was associated with backward walking only, perhaps due to it being more challenging. The association between BW velocity and executive function differed according to use of walking aids, which appeared to attenuate the association.

Bakgrund Tidigare forskning visar att sjuksköterskor har förutfattade meningar om patienter med en stigmatiserande diagnos. Sjuksköterskor stigmatiserar och har negativa attityder som påverkar deras vård av dessa patienter. Individer med substansbrukssyndrom är en grupp som är särskilt utsatt för stigmatisering i samhället. Dessa individer påträffas inom samtliga specialiteter inom vården. Denna studie fokuserar därför på sjuksköterskors upplevelse av patienter med substansbrukssyndrom. Syfte Syftet med denna studie var att studera sjuksköterskors upplevelser av att vårda patienter med substansbrukssyndrom. Metod Metoden som användes var en systematisk litteraturstudie med kvalitativ ansats. Huvudresultat Studiens resultat delas upp i “Substansbrukssyndrom som misslyckande eller sjukdom”, “Sjuksköterskans attityd till patienter med substansbrukssyndrom”, “Upplevda egenskaper hos patienter med substansbrukssyndrom”, “Patientens behov” och “Sjuksköterskors behov av utbildning”. Stigmatisering av substansbrukssyndrom medförde att sjuksköterskor förhöll sig till dessa patienter på olika sätt. Det berodde på om de såg på substansbrukssyndrom som ett misslyckande eller en sjukdom, vilket i sin tur påverkades av hur mycket kunskap sjuksköterskor hade om sjukdomen substansbrukssyndrom. Sjuksköterskor var mer eller mindre stigmatiserande vilket påverkade deras inställning till dessa patienter. Slutsats Ytterligare utbildning rekommenderas för att ge sjuksköterskor en bättre förståelse för patienters perspektiv. Det krävs vidare forskning inom området för att få en djupare förståelse om sjuksköterskors upplevelser om patienter med substansbrukssyndrom. Background Previous research shows that nurses have preconceived ideas of patients with a stigmatized disease. Nurses stigmatize and have negative attitudes that affect their care of these patients. Individuals with substance related disorders as a group are particularly prone to stigmatization in society. These individuals exist in all specialties of healthcare. This review therefore focuses on nurses’ experiences regarding patients with substance related disorders. Aim The purpose of this review was to investigate the nurses' experiences of caring for patients with substance related disorders. Method The method used was a systematic literature with qualitative approach. Findings The results are divided into "Substance related disorders as failure or disease," "The nurses attitude to patients with substance related disorders", "Perceived characteristics of patients with substance related disorders," "The patients’ needs" and "The nurses need of education. "The stigmatization of substance related disorders affected nurses’ attitudes towards these patients in a variety of ways. The attitude depended on whether nurses look at substance related disorders as a failure or as a disease. This was influenced by the nurses’ level of knowledge regarding substance related disorders. Nurses could be more or less stigmatizing, which would affect their approach to these patients. Conclusion Advanced training is recommended to give nurses a better understanding of patients ́ perspective. Further research is required in order to gain a deeper understanding of nurses' experiences regarding patients with substance related disorder.

Plants have tremendous capacity to adjust their morphology, physiology and metabolism in response to changes in growing conditions. Thus, analysis solely of plants grown under constant conditions m ...

Until now, there have been few assays to measure C-peptide and proinsulin in the rat. We used a well-established rat insulin ELISA and validated two novel ELISAs for rat C-peptide and rat/mouse proinsulin to examine secretion and content of insulin, proinsulin, and C-peptide from rat islets cultured for 72 h at different glucose concentrations in culture medium. To examine long-term effects in vitro rather than short-term effects of exposure to low, normal, and high glucose, the exposure time to the different glucose concentrations was set to 72 h. The measurement uncertainty of the values obtainable from the ELISAs was determined by calculation of the variation pattern from the intraassay variation generated by unknown samples, and repeatability was determined by analysis of controls. The precision study and the analysis of controls confirm that the validated ELISAs for rat C-peptide and proinsulin would be useful for further studies on the effects of preculture in different glucose concentrations. The higher the glucose concentration used during the 72-h culture period of rat islets, the higher insulin, C-peptide and proinsulin values were obtained in a subsequent short-term glucose-challenge experiment. The proportion of proinsulin to insulin secreted increased, as did islet content, with increasing glucose concentration during preculture. We also observed a nonequimolar, glucose-dependent secretion and content of rat insulin over rat C-peptide after culture at 11.1 and 28 mm glucose.

Prosurfactant protein C (proSP-C) is a 197-residue integral membrane protein, in which the C-terminal domain (CTC, positions 59–197) is localized in the endoplasmic reticulum (ER) lumen and contains a Brichos domain (positions 94–197). Mature SP-C corresponds largely to the transmembrane (TM) region of proSP-C. CTC binds to SP-C, provided that it is in nonhelical conformation, and can prevent formation of intracellular amyloid-like inclusions of proSP-C that harbor mutations linked to interstitial lung disease (ILD). Herein it is shown that expression of proSP-C (1–58), that is, the N-terminal propeptide and the TM region, in HEK293 cells results in virtually no detectable protein, while coexpression of CTC in trans yields SDS-soluble monomeric proSP-C (1–58). Recombinant human (rh) CTC binds to cellulose-bound peptides derived from the nonpolar TM region, but not the polar cytosolic part, of proSP-C, and requires ≥5-residues for maximal binding. Binding of rhCTC to a nonhelical peptide derived from SP-C results in α-helix formation provided that it contains a long TM segment. Finally, rhCTC and rhCTC Brichos domain shows very similar substrate specificities, but rhCTCL188Q, a mutation linked to ILD is unable to bind all peptides analyzed. These data indicate that the Brichos domain of proSP-C is a chaperone that induces α-helix formation of an aggregation-prone TM region.

Surfactant protein C (SP-C) constitutes the transmembrane part of prosurfactant protein C (proSP-C) and is α-helical in its native state. The C-terminal part of proSP-C (CTC) is localized in the endoplasmic reticulum lumen and binds to misfolded (β-strand) SP-C, thereby preventing its aggregation and amyloid fibril formation. In this study, we investigated the structure of recombinant human CTC and the effects of CTC–membrane interaction on protein structure. CTC forms noncovalent trimers and supratrimeric oligomers. It contains two intrachain disulfide bridges, and its secondary structure is significantly affected by urea or heat only after disulfide reduction. The postulated Brichos domain of CTC, with homologs found in proteins associated with amyloid and proliferative disease, is up to 1000-fold more protected from limited proteolysis than the rest of CTC. The protein exposes hydrophobic surfaces, as determined by CTC binding to the environment-sensitive fluorescent probe 1,1′-bis(4-anilino-5,5′-naphthalenesulfonate). Fluorescence energy transfer experiments further reveal close proximity between bound 1,1′-bis(4-anilino-5,5′-naphthalenesulfonate) and tyrosine residues in CTC, some of which are conserved in all Brichos domains. CTC binds to unilamellar phospholipid vesicles with low micromolar dissociation constants, and differential scanning calorimetry and CD analyses indicate that membrane-bound CTC is less structurally ordered than the unbound protein. The exposed hydrophobic surfaces and the structural disordering that result from interactions with phospholipid membranes suggest a mechanism whereby CTC binds to misfolded SP-C in the endoplasmic reticulum membrane.

Native lung surfactant protein C (SP-C) is a 4.2-kDa acylpeptide that associates with alveolar surfactant phospholipids via a transmembrane alpha-helix. This helix contains mainly Val, although poly-Val is inefficient in helix formation, and helical SP-C can spontaneously convert to beta-sheet aggregates and amyloid-like fibrils. SP-C is cleaved out from a 21-kDa integral membrane protein, proSP-C, in the alveolar type II cell. Recently several mutations localized in the endoplasmic reticulum-lumenal (C-terminal) part of proSP-C (CTproSP-C) have been associated with intracellular accumulation of toxic forms of proSP-C, low levels of mature SP-C, and development of interstitial lung disease. CTproSP-C contains a approximately 100-residue Brichos domain of unknown function that is also found in other membrane proteins associated with amyloid formation, dementia, and cancer. Here we find that recombinant CTproSP-C binds lipid-associated SP-C, which is in beta-strand conformation, and that this interaction results in an increased helical content. In contrast, CTproSP-C does not bind alpha-helical SP-C. Recombinant CTproSP-C(L188Q), a mutation associated with interstitial lung disease, shows secondary and quaternary structures similar to those of wild type CTproSP-C but is unable to bind lipid-associated beta-strand SP-C. Transfection of CTproSP-C into HEK293 cells that express proSP-C(L188Q) increases the amount of proSP-C protein, whereas no effect is seen on cells expressing wild type proSP-C. These findings suggest that CTproSP-C binds nonhelical SP-C and thereby prevents beta-sheet aggregation and that mutations in CTproSP-C can interfere with this function.

Non-melanoma skin cancers commonly contain Human Papillomavirus (HPV), but the types found have varied depending on the polymerase chain reaction (PCR) primer systems used. Whole genome amplified DNA (not amplified by any specific PCR primers) from 91 skin lesions [41 squamous cell skin carcinomas (SCCs), 8 keratoacanthomas, 22 actinic keratoses, 3 basal cell carcinomas and 17 SCCs in situ] were sequenced. All samples were sequenced both at 160 Mb and 1.8 Gb sequencing depth per sample. The sequences from 10 different HPVs in 47/91 specimens were found. Sequences represented four established HPV types (HPV types 16, 22, 120, 124), two previously known putative types (present in GenBank) and four previously unknown HPV sequences (new putative types). The most commonly detected virus was cloned, sequenced and designated as HPV197. Type-specific real-time PCR detected HPV197 in 34/91 specimens. For comparison, a pool of the same samples after general primer PCR amplification was also sequenced. This revealed 40 different HPVs, but only two HPV types were detected both with sequencing without prior PCR and with sequencing PCR amplicons, suggesting that sequencing without prior PCR gives a more unbiased representation of the HPVs present. In summary, it was found that HPV can be sequenced from most skin disease specimens and HPV197 appeared to be the most commonly present virus.

A subset of protein misfolding diseases, including, for example, Alzheimer's disease, is associated with the formation of highly insoluble amyloid fibrils with a beta-sheet structure. The amyloidogenic human lung surfactant protein C (SP-C) is generated from SP-C precursor, which has a C-terminal domain (CTC) that prevents SP-C amyloid fibril formation. Analysis of the substrate specificity of CTC reveals that it binds to all amino acid residues that promote membrane insertion, provided that they are in a nonhelical conformation. In line with this unexpectedly general substrate specificity, the anti-amyloid function of CTC extends to a transmembrane segment other than that of (pro)SP-C, namely, the amyloid beta-peptide associated with Alzheimer's disease. These findings indicate that CTC is the first known chaperone to be directed towards nonhelical transmembrane segments and that it may be employed for the development of new diagnostics or anti-amyloid therapies.

Fifteen catalysts were prepared by intermittently impregnating alumina washcoats with water solutions containing La3+, Co2+ and PdCl42- ions/complex and calcining them at 550-820 degrees C. The catalysts were evaluated with respect to light-off performance, at stationary and transient feed gas stoichiometry, respectively, and redox characteristics, using NO/CO/C3H6/O-2/N-2 gas mixtures to simulate car exhaust. Alumina supported Pd exhibited three-way activity, i.e., simultaneous oxidation of CO and C3H6 and reduction of NO in a narrow interval around stoichiometric composition of the feed gas. Compared to Pd alone, addition of La or Co caused a widening of the interval under net reducing conditions. Addition of Co to Pd caused a significant increase in the activities for oxidation of CO and C3H6 under stoichiometric conditions. The conversions of CO and C3H6 started at about 100 degrees lower temperatures over Co-promoted Pd compared to unpromoted Pd. A marked increase in the activity for the reduction of NO at transient conditions was observed over Co-promoted Pd compared to unpromoted Pd. The catalysts were characterized by X-ray powder diffraction, scanning electron microscopy, and transmission electron microscopy combined with energy-dispersive spectroscopy analysis, X-ray photoelectron spectroscopy (XPS), and specific surface area measurements. Only Co2+ could be detected by XPS in the surface layers of the Co-containing sample. A significant part of the cobalt is present in forms which can be oxidized and reduced under synthetic car exhaust conditions. These oxidizable/reducible cobalt sites are predominantly active for oxidation of CO and C3H6, hence promoting the reduction of NO over Pd by initiating these exothermic reactions in the catalyst.

Plants have tremendous capacity to adjust their morphology, physiology and metabolism in response to changes in growing conditions. Thus, analysis solely of plants grown under constant conditions may give partial or misleading indications of their responses to the fluctuating natural conditions in which they evolved. To obtain data on growth condition-dependent differences in metabolite levels, we compared leaf metabolite profiles of Arabidopsis thaliana growing under three constant laboratory light conditions: 30 [low light (LL)], 300 [normal light (NL)] and 600 [high light (HL)]µmol photons m(-2) s(-1). We also shifted plants to the field and followed their metabolite composition for 3 d. Numerous compounds showed light intensity-dependent accumulation, including: many sugars and sugar derivatives (fructose, sucrose, glucose, galactose and raffinose); tricarboxylic acid (TCA) cycle intermediates; and amino acids (ca. 30% of which were more abundant under HL and 60% under LL). However, the patterns differed after shifting NL plants to field conditions. Levels of most identified metabolites (mainly amino acids, sugars and TCA cycle intermediates) rose after 2 h and peaked after 73 h, indicative of a 'biphasic response' and 'circadian' effects. The results provide new insight into metabolomic level mechanisms of plant acclimation, and highlight the role of known protectants under natural conditions.

Arabidopsis is naturally adapted to habitats in which both biotic variables (e.g., light, wind, and humidity) and abiotic variables (e.g., competition, herbivory, and pathogen densities) strongly fluctuate. Hence, conditions in controlled growth chambers (in which Arabidopsis is typically grown for scientific experiments) differ substantially from those in natural environments. In order to mimic more closely natural conditions, we grow Arabidopsis outdoors under "semi-natural" field conditions. Performing experiments on transgenic Arabidopsis grown in the field that are sufficiently reliable for publication is challenging. In this chapter, we present some of our experiences based on 10 years of field experimentation, which may be of use to researchers seeking to perform field experiments using transgenic Arabidopsis.