Mechanism-Informed Refinement Reveals Altered Substrate-Binding Mode for Catalytically Competent Nitroreductase

Nitroreductase from Enterobacter cloacae (NR) reduces diverse nitroaromatics including herbicides, explosives and prodrugs, and holds promise for bioremediation, prodrug activation and enzyme-assisted synthesis. We solved crystal structures of NR complexes with bound substrate or analog for each of its two half-reactions. We complemented these with kinetic isotope effect (KIE) measurements elucidating H-transfer steps essential to each half-reaction. KIEs indicate hydride transfer from NADH to the flavin consistent with our structure of NR with the NADH analog nicotinic acid adenine dinucleotide (NAAD). The KIE on reduction of p-nitrobenzoic acid (p-NBA) also indicates hydride transfer, and requires revision of prior computational mechanisms. Our mechanistic information provided a structural restraint for the orientation of bound substrate, placing the nitro group closer to the flavin N5 in the pocket that binds the amide of NADH. KIEs show that solvent provides a proton, enabling accommodation of different nitro group placements, consistent with NR’s broad repertoire

Characteristics of Cognitive Behavioral Therapy for Older Adults Living in Residential Care: Protocol for a Systematic Review

Background: The prevalence rates of depressive and anxiety disorders are high in residential aged care settings. Older adults in such settings might be prone to these disorders because of losses associated with transitioning to residential care, uncertainty about the future, as well as a decline in personal autonomy, health, and cognition. Cognitive behavioral therapy (CBT) is efficacious in treating late-life depression and anxiety. However, there remains a dearth of studies examining CBT in residential settings compared with community settings. Typically, older adults living in residential settings have higher care needs than those living in the community. To date, no systematic reviews have been conducted on the content and the delivery characteristics of CBT for older adults living in residential aged care settings. Objective: The objective of this paper is to describe the systematic review protocol on the characteristics of CBT for depression and/or anxiety for older adults living in residential aged care settings. Methods: This protocol was developed in compliance with the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Studies that fulfill the inclusion criteria will be identified by systematically searching relevant electronic databases, reference lists, and citation indexes. In addition, the PRISMA flowchart will be used to record the selection process. A pilot-tested data collection form will be used to extract and record data from the included studies. Two reviewers will be involved in screening the titles and abstracts of retrieved records, screening the full text of potentially relevant reports, and extracting data. Then, the delivery and content characteristics of different CBT programs of the included studies, where available, will be summarized in a table. Furthermore, the Downs and Black checklist will be used to assess the methodological quality of the included studies. Results: Systematic searches will commence in May 2018, and data extraction is expected to commence in July 2018. Data analyses and writing will happen in October 2018. Conclusions: In this section, the limitations of the systematic review will be outlined. Clinical implications for treating late-life depression and/or anxiety, and implications for residential care facilities will be discussed

Fundamental Limits on Wavelength, Efficiency and Yield of the Charge Separation Triad

In an attempt to optimize a high yield, high efficiency artificial photosynthetic protein we have discovered unique energy and spatial architecture limits which apply to all light-activated photosynthetic systems. We have generated an analytical solution for the time behavior of the core three cofactor charge separation element in photosynthesis, the photosynthetic cofactor triad, and explored the functional consequences of its makeup including its architecture, the reduction potentials of its components, and the absorption energy of the light absorbing primary-donor cofactor. Our primary findings are two: First, that a high efficiency, high yield triad will have an absorption frequency more than twice the reorganization energy of the first electron transfer, and second, that the relative distance of the acceptor and the donor from the primary-donor plays an important role in determining the yields, with the highest efficiency, highest yield architecture having the light absorbing cofactor closest to the acceptor. Surprisingly, despite the increased complexity found in natural solar energy conversion proteins, we find that the construction of this central triad in natural systems matches these predictions. Our analysis thus not only suggests explanations for some aspects of the makeup of natural photosynthetic systems, it also provides specific design criteria necessary to create high efficiency, high yield artificial protein-based triads

Cognitive behavioural therapy (CBT) for anxiety in people with dementia: study protocol for a randomised controlled trial

Background Many people with dementia experience anxiety, which can lead to decreased independence, relationship difficulties and increased admittance to care homes. Anxiety is often treated with antipsychotic medication, which has limited efficacy and serious side effects. Cognitive behavioural therapy (CBT) is widely used to treat anxiety in a range of populations, yet no RCTs on CBT for anxiety in dementia exist. This study aims to develop a CBT for anxiety in dementia manual and to determine its feasibility in a pilot RCT. Methods/design Phase I involves the development of a CBT for anxiety in dementia manual, through a process of (1) focus groups, (2) comprehensive literature reviews, (3) expert consultation, (4) a consensus conference and (5) field testing. Phase II involves the evaluation of the manual with 50 participants with mild to moderate dementia and anxiety (and their carers) in a pilot, two-armed RCT. Participants will receive either ten sessions of CBT or treatment as usual. Primary outcome measures are anxiety and costs. Secondary outcome measures are participant quality of life, behavioural disturbance, cognition, depression, mood and perceived relationship with the carer, and carer mood and perceived relationship with the person with dementia. Measures will be administered at baseline, 15 weeks and 6 months. Approximately 12 qualitative interviews will be used to gather service-users' perspectives on the intervention. Discussion This study aims to determine the feasibility of CBT for people with anxiety and dementia and provide data on the effect size of the intervention in order to conduct a power analysis for a definitive RCT. The manual will be revised according to qualitative and quantitative findings. Its publication will enable its availability throughout the NHS and beyond. Trial registration ISRCTN6480685

A synthetic biological quantum optical system

In strong plasmon–exciton coupling, a surface plasmon mode is coupled to an array of localized emitters to yield new hybrid light–matter states (plexcitons), whose properties may in principle be controlled via modification of the arrangement of emitters. We show that plasmon modes are strongly coupled to synthetic light-harvesting maquette proteins, and that the coupling can be controlled via alteration of the protein structure. For maquettes with a single chlorin binding site, the exciton energy (2.06 ± 0.07 eV) is close to the expected energy of the Qy transition. However, for maquettes containing two chlorin binding sites that are collinear in the field direction, an exciton energy of 2.20 ± 0.01 eV is obtained, intermediate between the energies of the Qx and Qy transitions of the chlorin. This observation is attributed to strong coupling of the LSPR to an H-dimer state not observed under weak coupling

A survey of Australian psychologists in aged care: the relationship between training, attitudes and professional practice with older clients\ud

The proportion of Australian adults aged over 65 years is due to increase over the next\ud 20 years with corresponding increases in mental illness. A growing demand for clinical\ud psychology services to older adults is expected yet overseas surveys indicate a low rate\ud of specializing in working with the over-65 age group. The status of geropsychology in\ud Australia is examined through exploratory analysis of survey data from a practising\ud psychologist sample and from a post-graduate psychology trainee sample. Six published\ud studies are reported that examine the relationship among training, personal contact and\ud attitudes, and the relative contributions of these three factors to decisions on working\ud with older adults among Australian psychologists. Pilot research highlights the\ud importance of interest in working with older clients and additional training external to\ud formal degree courses in discriminating between those psychologists who specialised in\ud aged care compared to generalist practitioners. A national survey of psychologists\ud identifies clinical exposure to older adults while training and negative expectations of\ud subjective ageing as additional factors predicting specialist category membership. Low\ud rates of professional involvement with older clients in general highlight the\ud corresponding dearth of psychologists specialising in aged care service provision, a\ud finding congruent with overseas research. The positive influence of clinical contact, as\ud opposed to the absence of predictive ability for personal contact, is also emphasized in a\ud survey of post-graduate psychology students. Professional attitudes, such as confidence\ud and interest in working with older adults, are other predictors of interest in working\ud with older clients among students. The use of the Reactions to Ageing Questionnaire in several analyses also highlights the importance of affect in influencing behaviour, with\ud professional attitudes predicting personal attitudes towards ageing, as opposed to\ud personal contact or formal training. The final study underscores the role of contextual\ud relevance, with training contributing to more variance in interest in working with older\ud adults among trainees, as compared to practitioners whose professional interest was\ud influenced more by attitudes. The contact hypothesis is not confirmed in this research in\ud either the student or the practitioner samples. Strategies to promote the field of clinical\ud geropsychology across a variety of settings, ranging from training to clinical service\ud delivery are discussed

Psychology in practice: Guidelines for the provision of psychological services for older adults

The practice of psychology covers the range of ages from conception through to the end of life and palliative care. Psychologists practice in a variety of roles, but the majority of these roles involve interactions with nonprofessionals of varying ages. These interactions are governed by codes of ethical practice, whether these are developed by the funding bodies for research activities, professional associations, or regulatory bodies. Ethical codes vary in their format and emphasis, but all have the protection of the public as a major purpose. Often there are special provisions in these codes for particular populations or circumstances. Here we describe the development of ethical guidelines for the practice of psychology with older adults in Australia and report on those guidelines and their supporting literature