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The conversion of a soluble protein into polymeric amyloid structures is a process that is poorly understood. Here, we describe a fully redox-regulated amyloid system in which cysteine oxidation of the tumor suppressor protein p16INK4a leads to rapid amyloid formation. We identify a partially-structured disulfide-bonded dimeric intermediate species that subsequently assembles into fibrils. The stable amyloid structures disassemble when the disulfide bond is reduced. p16INK4a is frequently mutated in cancers and is considered highly vulnerable to single-point mutations. We find that multiple cancer-related mutations show increased amyloid formation propensity whereas mutations stabilizing the fold prevent transition into amyloid. The complex transition into amyloids and their structural stability is therefore strictly governed by redox reactions and a single regulatory disulfide bond. The conversion of a soluble protein into polymeric amyloid structures is poorly understood. Here the authors report that the tumor suppressor protein p16INK4a changes its structure upon oxidation to form aggregated amyloid fibrils, which are fully reversible upon disulfide bond reduction. [ABSTRACT FROM AUTHOR]

The effect of population bottlenecks and genome reduction on enzyme function is poorly understood. Candidatus Liberibacter solanacearum is a bacterium with a reduced genome that is transmitted vertically to the egg of an infected psyllid—a population bottleneck that imposes genetic drift and is predicted to affect protein structure and function. Here, we define the function of Ca. L. solanacearum dihydrodipicolinate synthase (CLsoDHDPS), which catalyzes the committed branchpoint reaction in diaminopimelate and lysine biosynthesis. We demonstrate that CLsoDHDPS is expressed in Ca. L. solanacearum and expression is increased ~2‐fold in the insect host compared to in planta. CLsoDHDPS has decreased thermal stability and increased aggregation propensity, implying mutations have destabilized the enzyme but are compensated for through elevated chaperone expression and a stabilized oligomeric state. CLsoDHDPS uses a ternary‐complex kinetic mechanism, which is to date unique among DHDPS enzymes, has unusually low catalytic ability, but an unusually high substrate affinity. Structural studies demonstrate that the active site is more open, and the structure of CLsoDHDPS with both pyruvate and the substrate analogue succinic‐semialdehyde reveals that the product is both structurally and energetically different and therefore evolution has in this case fashioned a new enzyme. Our study suggests the effects of genome reduction and genetic drift on the function of essential enzymes and provides insights on bacteria‐host co‐evolutionary associations. We propose that bacteria with endosymbiotic lifestyles present a rich vein of interesting enzymes useful for understanding enzyme function and/or informing protein engineering efforts. [ABSTRACT FROM AUTHOR]

There is a paucity of research surrounding the needs of those within forensic mental health populations. This gap is amplified when we examine CBT-based treatments for those with anger and aggression in this population. Before we can address this gap in the literature, we must survey what has been done, who it has been applied to, and how effective it has been. Thus, we aimed to conduct a review on CBT for anger and aggression among forensic mental health populations. Authors followed a preregistered Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocol. Databases were searched for articles April 2020 and October 2022. The searches resulted in 4,137 articles which were reduced to 22 after applying inclusion and exclusion criteria. Findings demonstrate that CBT treatments for anger and aggression, including the reasoning and rehabilitation program, dialectic behaviour therapy, and aggression control programs tend to produce consistent and favourable results within forensic mental health populations. Findings confirm the success of CBT-based treatments for anger and aggression within this subgroup of justice-involved individuals. The review expands on this notion by identifying which treatments and criteria appear to be most promising for individuals in the forensic mental health population. [ABSTRACT FROM AUTHOR]

Acute myeloid leukaemia (AML) is characterized by impaired myeloid differentiation resulting in an accumulation of immature blasts in the bone marrow and peripheral blood. Although AML can occur at any age, the incidence peaks at age 65. The pathobiology of AML also varies with age with associated differences in incidence, as well as the frequency of cytogenetic change and somatic mutations. In addition, 5-year survival rates in paediatrics are 60–75% but fall to 5–15% in older AML patients. This systematic review aimed to determine whether the altered genes in AML affect the same molecular pathways, indifferent of patient age, and, therefore, whether patients could benefit from the repurposing drugs or the use of the same immunotherapeutic strategies across age boundaries to prevent relapse. Using a PICO framework and PRISMA-P checklist, relevant publications were identified using five literature databases and assessed against an inclusion criteria, leaving 36 articles, and 71 targets for therapy, for further analysis. QUADAS-2 was used to determine the risk of bias and perform a quality control step. We then priority-ranked the list of cancer antigens based on predefined and pre-weighted objective criteria as part of an analytical hierarchy process used for dealing with complex decisions. This organized the antigens according to their potential to act as targets for the immunotherapy of AML, a treatment that offers an opportunity to remove residual leukaemia cells at first remission and improve survival rates. It was found that 80% of the top 20 antigens identified in paediatric AML were also within the 20 highest scoring immunotherapy targets in adult AML. To analyse the relationships between the targets and their link to different molecular pathways, PANTHER and STRING analyses were performed on the 20 highest scoring immunotherapy targets for both adult and paediatric AML. There were many similarities in the PANTHER and STRING results, including the most prominent pathways being angiogenesis and inflammation mediated by chemokine and cytokine signalling pathways. The coincidence of targets suggests that the repurposing of immunotherapy drugs across age boundaries could benefit AML patients, especially when used in combination with conventional therapies. However, due to cost implications, we would recommend that efforts are focused on ways to target the highest scoring antigens, such as WT1, NRAS, IDH1 and TP53, although in the future other candidates may prove successful. [ABSTRACT FROM AUTHOR]

Background: Gray's original Reinforcement Sensitivity Theory (RST) posits that an oversensitive behavioral inhibition system (BIS) may increase risk for negative-reinforcement-motivated drinking, given its role in anxiety. However, existing data provides mixed support for the BIS-alcohol use association. The inconsistent evidence is not surprising, as the revised RST predicts that the behavioral approach system (BAS) should moderate the effect of the BIS on alcohol use. A strong BAS is thought to bring attention to the negatively reinforcing effects of alcohol, leading to problem drinking among those with a strong BIS. While emerging results support this interaction, we still have much to learn about the mechanisms underlying this effect on alcohol use. Accordingly, we examined motives for alcohol use as mediators of the joint associations of the BIS and the BAS on drinking behaviors. Specifically, our central hypothesis was that individuals with a strong BIS and a strong BAS would endorse increased negative reinforcement motives for drinking (coping and conformity motives), which in turn would predict heavy drinking and alcohol problems. Method: Participants (N=346; 195 women) completed study measures as part of the baseline assessment for a larger study. Results: Overall, results partially supported the hypotheses. Mediated moderation analyses showed that the indirect effect of the BIS on alcohol problems, through coping and conformity motives, was strongest at high levels of the BAS. This effect was not supported for alcohol use. Conclusions: Our findings suggest that clinical interventions should target coping and conformity reasons for drinking among anxious, reward responsive, young adults. [ABSTRACT FROM AUTHOR]

Background and aims: Problem gambling and tobacco use are highly comorbid among adults. However, there are few treatment frameworks that target both gambling and tobacco use simultaneously (i.e., an integrated approach), while also being accessible and evidence-based. The aim of this two-arm open label RCT was to examine the efficacy of an integrated online treatment for problem gambling and tobacco use. Methods: A sample of 209 participants (Mage = 37.66, SD = 13.81; 62.2% female) from North America were randomized into one of two treatment conditions (integrated [n = 91] or gambling only [n = 118]) that lasted for eight weeks and consisted of seven online modules. Participants completed assessments at baseline, after treatment completion, and at 24-week follow-up. Results: While a priori planned generalized linear mixed models showed no condition differences on primary (gambling days, money spent, time spent) and secondary outcomes, both conditions did appear to significantly reduce problem gambling and smoking behaviours over time. Post hoc analyses showed that reductions in smoking and gambling craving were correlated with reductions in days spent gambling, as well as with gambling disorder symptoms. Relatively high (versus low) nicotine replacement therapy use was associated with greater reductions in gambling behaviours in the integrated treatment condition. Discussion and conclusions: While our open label RCT does not support a clear benefit of integrated treatment, findings suggest that changes in smoking and gambling were correlated over time, regardless of treatment condition, suggesting that more research on mechanisms of smoking outcomes in the context of gambling treatment may be relevant. [ABSTRACT FROM AUTHOR]

Introduction: Disruption of cortical gray matter and white matter tracts are well‐established markers of alcohol use disorder (AUD), but less is known about whether similar differences are present in intracortical myelin (ICM, i.e., highly myelinated gray matter in deeper cortical layers). The goal of this study was to provide initial proof‐of‐concept for using an optimized structural magnetic resonance imaging (MRI) sequence to detect differences in ICM in individuals with AUD compared to control participants reporting drinking within recommended guidelines. Methods: This study used an optimized 3T MRI sequence for high intracortical contrast to examine ICM‐related MRI signal in 30 individuals with AUD and 33 healthy social drinkers. Surface‐based analytic techniques were used to quantify ICM‐related MRI signal in 20 bilateral a priori regions of interest based on prior cortical thickness studies, and exploratory vertex‐wise analyses were examined using Cohen's d effect size. Results: The global distribution of ICM‐related signal was largely comparable between groups. Region of interest analysis indicated that AUD group exhibited greater ICM‐related MRI signal in precuneus, ventromedial prefrontal cortex, posterior cingulate, middle anterior cingulate, middle/posterior insula, and dorsolateral prefrontal cortex (Cohen's ds = 0.50–0.75). Four regions (right precuneus, ventromedial prefrontal cortex, posterior cingulate and left dorsolateral prefrontal cortex) remained significant (p <.05) after covarying for smoking status. Conclusion: These findings provide initial evidence of ICM differences in a moderately sized sample of individuals with AUD compared to controls, although the inflation of type 1 error rate necessitates caution in drawing conclusions. Robustly establishing these differences in larger samples is necessary. The cross‐sectional design cannot address whether the observed differences predate AUD or are consequences of heavy alcohol consumption. [ABSTRACT FROM AUTHOR]

Summary: Ethical, environmental and health concerns around dairy products are driving a fast‐growing industry for plant‐based dairy alternatives, but undesirable flavours and textures in available products are limiting their uptake into the mainstream. The molecular processes initiated during fermentation by lactic acid bacteria in dairy products is well understood, such as proteolysis of caseins into peptides and amino acids, and the utilisation of carbohydrates to form lactic acid and exopolysaccharides. These processes are fundamental to developing the flavour and texture of fermented dairy products like cheese and yoghurt, yet how these processes work in plant‐based alternatives is poorly understood. With this knowledge, bespoke fermentative processes could be engineered for specific food qualities in plant‐based foods. This review will provide an overview of recent research that reveals how fermentation occurs in plant‐based milk, with a focus on how differences in plant proteins and carbohydrate structure affect how they undergo the fermentation process. The practical aspects of how this knowledge has been used to develop plant‐based cheeses and yoghurts is also discussed. [ABSTRACT FROM AUTHOR]

Background: We conducted a longitudinal study to examine person‐centered heterogeneity in problem drinking risk during the 2019 Coronavirus disease (COVID‐19) pandemic. We aimed to differentiate high‐ from low‐risk subgroups of drinkers during the pandemic, to report on the longitudinal follow‐up of the baseline sample reported in Wardell et al. (Alcohol Clin Exp Res, 44, 2020, 2073), and to examine how subgroups of drinkers differed on coping‐related and pre‐pandemic alcohol vulnerability factors. Methods: Canadian alcohol users (N = 364) were recruited for the study. Participants completed surveys at four waves (spaced 3 months apart), with the first being 7 to 8 weeks after the COVID‐19 state of emergency began in Canada. The data were analyzed using a parallel process latent growth class analysis followed by general linear mixed models analysis. Results: We found evidence for three latent classes: individuals who increased drinking (class 1; n = 23), low‐risk drinkers (class 2; n = 311), and individuals who decreased drinking (class 3; n = 30). Participants who increased (vs. those who decreased) problem drinking during the pandemic struggled with increasing levels of social disconnection and were also increasingly more likely to report drinking to cope with these issues. Those in the increasing class (relative to low‐risk drinkers) reported increasing levels of depression during the study. Relative to low‐risk drinkers, participants in the increasing class had higher pre‐pandemic AUDIT scores, greater frequency of solitary drinking, and higher alcohol demand. Interestingly, participants in the decreasing class had the highest pre‐pandemic AUDIT scores. Conclusions: We examined longitudinal data to identify subgroups of drinkers during the pandemic and to identify factors that may have contributed to increased problem drinking. Findings suggest that while most of the sample did not change their alcohol use, a small portion of individuals escalated use, while a small portion decreased their drinking. Identifying the vulnerability factors associated with increased drinking could aid in the development of preventative strategies and intervention approaches. [ABSTRACT FROM AUTHOR]

Background: There are concerns that the coronavirus disease 2019 (COVID‐19) pandemic may increase drinking, but most accounts to date are cross‐sectional studies of self‐attributions about alcohol‐related impacts and the accuracy of those perceptions has not been investigated. The current study examined the correspondence between self‐attributions of pandemic‐related changes in drinking and longitudinally‐measured changes in drinking and alcohol‐related consequences in a sample of emerging adults. Methods: In an existing ongoing longitudinal study on alcohol misuse (≥1 heavy episodic drinking day/month) in emerging adults, 473 individuals (Mage = 23.8; 41.7% male) received a supplemental assessment from June 17th to July 1st, 2020, during public health restrictions in Ontario, Canada. These intrapandemic data were matched to the most recent assessment prior to the pandemic (~8 months earlier). Self‐attributions about changes in drinking were assessed globally (i.e., increases/decreases/no change) and with higher resolution questions clarifying the magnitude of changes. Results: Global self‐attributions about changes in drinking substantively paralleled longitudinal changes in weekly drinking days (DD). In the longitudinal data, individuals' who self‐reported increases in drinking exhibited significant increases; individuals' who self‐reported decreases exhibited significant decreases; and individuals who self‐reported no change exhibited nonsignificant changes. Higher resolution items likewise revealed longitudinal patterns of weekly drinking that were substantively consistent with self‐attributions. Heavy DD and alcohol‐related consequences exhibited similar patterns, but only individuals who self‐reported large increases in drinking exhibited increases on these outcomes. Individuals who reported large increases in drinking also exhibited significant increases in depression and posttraumatic stress disorder symptoms. Conclusions: Self‐attributions about drinking closely corresponded to longitudinal changes in drinking, supporting the validity of self‐attributions in population‐level surveys, particularly in young adults. Notably, a subgroup was identified that exhibited pronounced increases for all alcohol‐related outcomes and concurrent increases in internalizing psychopathology. [ABSTRACT FROM AUTHOR]

The article discusses the challenges faced by Francophone patients in accessing appropriate linguistic care in health care settings in Canada. Despite a high level of bilingualism in the Francophone population, the distribution of French-speaking physicians does not match the distribution of the Francophone population, leading to a lack of linguistic concordance. The article suggests that physicians should actively identify Francophone patients in their practice and use an active offer approach, which involves proactively offering French-language services. Non-French-speaking physicians are encouraged to use interpreters when interacting with Francophone patients, and efforts should be made to provide French-language continuity of care. [Extracted from the article]

Importance: Delay discounting is a behavioral economic index of impulsive preferences for smaller-immediate or larger-delayed rewards that is argued to be a transdiagnostic process across health conditions. Studies suggest some psychiatric disorders are associated with differences in discounting compared with controls, but null findings have also been reported.Objective: To conduct a meta-analysis of the published literature on delay discounting in people with psychiatric disorders.Data Sources: PubMed, MEDLINE, PsycInfo, Embase, and Web of Science databases were searched through December 10, 2018. The psychiatric keywords used were based on DSM-IV or DSM-5 diagnostic categories. Collected data were analyzed from December 10, 2018, through June 1, 2019.Study Selection: Following a preregistered Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol, 2 independent raters reviewed titles, abstracts, and full-text articles. English-language articles comparing monetary delay discounting between participants with psychiatric disorders and controls were included.Data Extraction and Synthesis: Hedges g effect sizes were computed and random-effects models were used for all analyses. Heterogeneity statistics, one-study-removed analyses, and publication bias indices were also examined.Main Outcomes and Measures: Categorical comparisons of delay discounting between a psychiatric group and a control group.Results: The sample included 57 effect sizes from 43 studies across 8 diagnostic categories. Significantly steeper discounting for individuals with a psychiatric disorder compared with controls was observed for major depressive disorder (Hedges g = 0.37; P = .002; k = 7), schizophrenia (Hedges g = 0.46; P = .004; k = 12), borderline personality disorder (Hedges g = 0.60; P < .001; k = 8), bipolar disorder (Hedges g = 0.68; P < .001; k = 4), bulimia nervosa (Hedges g = 0.41; P = .001; k = 4), and binge-eating disorder (Hedges g = 0.34; P = .001; k = 7). In contrast, anorexia nervosa exhibited statistically significantly shallower discounting (Hedges g = -0.30; P < .001; k = 10). Modest evidence of publication bias was indicated by a statistically significant Egger test for schizophrenia and at the aggregate level across studies.Conclusions and Relevance: Results of this study appear to provide empirical support for delay discounting as a transdiagnostic process across most of the psychiatric disorders examined; the literature search also revealed limited studies in some disorders, notably posttraumatic stress disorder, which is a priority area for research. [ABSTRACT FROM AUTHOR]

Background: Previous neuroimaging studies examining relations between alcohol misuse and cortical thickness have revealed that increased drinking quantity and alcohol‐related problems are associated with thinner cortex. Although conflicting regional effects are often observed, associations are generally localized to frontal regions (e.g., dorsolateral prefrontal cortex [DLPFC], inferior frontal gyrus [IFG], and anterior cingulate cortex). Inconsistent findings may be attributed to methodological differences, modest sample sizes, and limited consideration of sex differences. Methods: This study examined neuroanatomical correlates of drinking quantity and heavy episodic drinking in a large sample of younger adults (N = 706; Mage = 28.8; 51% female) using magnetic resonance imaging data from the Human Connectome Project. Exploratory analyses examined neuroanatomical correlates of executive function (flanker task) and working memory (list sorting). Results: Hierarchical linear regression models (controlling for age, sex, education, income, smoking, drug use, twin status, and intracranial volume) revealed significant inverse associations between drinks in past week and frequency of heavy drinking and cortical thickness in a majority of regions examined. The largest effect sizes were found for frontal regions (DLPFC, IFG, and the precentral gyrus). Follow‐up regression models revealed that the left DLPFC was uniquely associated with both drinking variables. Sex differences were also observed, with significant effects largely specific to men. Conclusions: This study adds to the understanding of brain correlates of alcohol use in a large, gender‐balanced sample of younger adults. Although the cross‐sectional methodology precludes causal inferences, these findings provide a foundation for rigorous hypothesis testing in future longitudinal investigations. [ABSTRACT FROM AUTHOR]

Deficits in impulse control have been linked to criminal offending, risk of recidivism, and other maladaptive behaviours relevant to the criminal justice system (e.g. substance use). Impulse control can be conceptualized as encompassing the broad domains of response inhibition and impulsive/risky decision-making. Advancements in technology have led to the development of computerized behavioural measures to assess performance in these domains, such as go/no-go and delay discounting tasks. Despite a relatively large literature examining these tasks in offenders, findings are not universally consistent. This systematic review aims to synthesize the literature using computerized neurocognitive tasks to assess two domains of impulse control in offenders: response inhibition and impulsive/risky decision-making. The review included 28 studies from diverse geographic locations, settings, and offender populations. The results largely support the general conclusion that offenders exhibit deficits in impulse control compared with non-offenders, with studies of response inhibition more consistently reporting differences than studies using impulsive and risky decision-making tasks. Findings are discussed in the context of contemporary neuroimaging research emphasizing dysfunction in prefrontal cortex as a key contributor to impulse control deficits in offenders. [ABSTRACT FROM AUTHOR]

Using NMR to probe transient binding of Aβ1–40 monomers to fibers, we find partially bound conformations with the highest degree of interaction near F19–K28 and a lesser degree of interaction near the C-terminus (L34–G37). This represents a shift away from the KLVFFA recognition sequence (residues 16–21) currently used for inhibitor design. [ABSTRACT FROM AUTHOR]

Background and Aims: The evolving legal status of cannabis world‐wide necessitates evidence‐based regulatory policies to minimize risks associated with cannabis misuse. A prominent concern is the impact legalization may have on the illegal cannabis market, including whether illegal cannabis will serve as a substitute for legal cannabis. Empirical data on this issue are virtually non‐existent. This study used behavioral economics to investigate substitutability of legal and illegal cannabis in legalized catchment areas in the United States. Design A substitution‐based marijuana purchase task assessed estimated cannabis consumption from concurrently available legal (a dispensary) and illegal (a dealer) sources. Prices of the two options were reciprocally either held constant ($10/gram) or escalated ($0–$60/gram). Setting: US states with legalized recreational cannabis. Participants: Adult cannabis users who were at least 21 years old (n = 724; mean age = 34.13; 52% female; 74% Caucasian) were recruited using online crowdsourcing. Measurements: Mean consumption values were used in demand curve modeling to generate indices of price sensitivity and elasticity. Differences in demand indices were compared using extra sums‐of‐squares F‐tests. Findings Both legal and illegal fixed‐price cannabis options had significant positive cross‐price elasticities (Ps < 0.001), indicating that higher prices motivate substitution irrespective of legality. However, the presence of a legal alternative had a substantially greater effect on consumption and elasticity of illegal cannabis (∆elasticity = 0.0019; F(1,37) = 160, P < 0.0001) than the presence of an illegal alternative on demand for legal cannabis (∆elasticity = 0.0002; F(1,37) = 48, P < 0.0001), indicating asymmetric substitution. Demand for legal cannabis was significantly greater than for illegal cannabis (P < 0.0001). Conclusions: Cannabis users treat legal cannabis as a superior commodity compared with illegal cannabis and exhibit asymmetric substitutability favoring legal product. Cannabis price policies that include somewhat higher consumer costs for legal cannabis relative to contraband (but not excessively higher costs) would not be expected to incentivize and expand the illegal market. [ABSTRACT FROM AUTHOR]

Objective: Co-use of cannabis and alcohol is associated with increased drinking and other negative consequences relative to use of alcohol alone. One potential explanation for these differences is overvaluation of alcohol (e.g., alcohol demand) among co-users, similar to established overvaluation of alcohol among tobacco and alcohol co-users. This study examined differences in alcohol demand between an alcohol and cannabis co-user group and an alcohol-only group.Method: A large sample of adult drinkers (n = 1,643, 54% female) was recruited through an online crowdsourcing site (Amazon Mechanical Turk). Of the full sample, 476 participants reported weekly or greater cannabis use in the past 6 months (co-user group); 888 reported never using cannabis in the past 6 months (alcohol-only group). Assessments included a validated alcohol purchase task and self-report measures of alcohol and cannabis use.Results: Co-users reported significantly higher alcohol consumption across the elastic portion of the alcohol demand curve (i.e., $1.50-$9.00/drink). Analyses of covariance controlling for alcohol use and demographics revealed significantly higher breakpoint (p = .025) and Omax (p = .002) and significantly lower elasticity (p < .003) in the co-user group. Intensity and Pmax did not significantly differ between groups.Conclusions: Co-users of cannabis and alcohol overvalue alcohol compared with individuals who drink alcohol but do not use cannabis. This study is generally consistent with prior studies on alcohol and tobacco co-users, providing converging evidence that polysubstance use is associated with overvaluation of alcohol. These findings have important implications for treatment and prevention, particularly in the context of changes in cannabis legalization. [ABSTRACT FROM AUTHOR]

The article cites a research study that examines the role of the neuronal S100B protein as suppressor of amyloid-beta aggregation and toxicity. Amyloid-beta aggregation and neuroinflammation are said to be strong candidates for the initiation of neurodegeneration. The structural details of the interaction between monomeric amyloid-beta aggregation and S100B are determined in the study.

In this review we discuss the divergent role of two closely related cytokines, IL-12 and IL-23, in shaping immune responses. In light of current therapeutic developments using biologic agents to block these two pathways, a better understanding of the immunological function of these cytokines is pivotal. [ABSTRACT FROM AUTHOR]

Little structural information is available so far on amyloid fibrils consisting of immunoglobulin light chains. It is not understood which features of the primary sequence of the protein result in fibril formation. We report here MAS solid-state NMR studies to identify the structured core of κ-type variable domain light chain fibrils. The core contains residues of the CDR2 and the β-strands D, E, F and G of the native immunoglobulin fold. The assigned core region of the fibril is distinct in comparison to the core identified in a previous solid-state NMR study on AL-09 by Piehl at. al, suggesting that VL fibrils can adopt different topologies. In addition, we investigated a soluble oligomeric intermediate state, previously termed the alternatively folded state (AFS), using NMR and FTIR spectroscopy. The NMR oligomer spectra display a high degree of similarity when compared to the fibril spectra, indicating a high structural similarity of the two aggregation states. Based on comparison to the native state NMR chemical shifts, we suggest that fibril formation via domain-swapping seems unlikely. Moreover, we used our results to test the quality of different amyloid prediction algorithms. [ABSTRACT FROM AUTHOR]

Hydrophobins are small proteins secreted by fungi and which spontaneously assemble into amphipathic layers at hydrophilic-hydrophobic interfaces. We have examined the self-assembly of the Class I hydrophobins EASAIS and Dew A, the Class II hydrophobin NC2 and an engineered chimeric hydrophobin. These Class I hydrophobins form layers composed of laterally associated fibrils with an underlying amyloid structure. These two Class I hydrophobins, despite showing significant conformational differences in solution, self-assemble to form fibrillar layers with very similar structures and require a hydrophilic-hydrophobic interface to trigger self-assembly. Addition of additives that influence surface tension can be used to manipulate the fine structure of the protein films. The Class II hydrophobin NC2 forms a mesh-like protein network and the engineered chimeric hydrophobin displays two multimeric forms, depending on assembly conditions. When formed on a graphite surface, the fibrillar EASAIS layers are resistant to alcohol, acid and basic washes. In contrast, the NC2 Class II monolayers are dissociated by alcohol treatment but are relatively stable towards acid and base washes. The engineered chimeric Class I/II hydrophobin shows increased stability towards alcohol and acid and base washes. Self-assembled hydrophobin films may have extensive applications in biotechnology where biocompatible; amphipathic coatings facilitate the functionalization of nanomaterials. [ABSTRACT FROM AUTHOR]