Characterisation of the Cytochrome P450 Monooxygenase CYP116B46 from Tepidiphilus thermophilus as a Homogentisic Acid Generating Enzyme and its Conversion to a Peroxygenase.

The heme enzymes of the cytochrome P450 superfamily (CYPs) catalyse the selective hydroxylation of unactivated C-H bonds in organic molecules. There is great interest in applying these enzymes as biocatalysts with a focus on self-sufficient CYP 'fusion' enzymes, comprising a single polypeptide chain with the electron transfer components joined to the heme domain. Here we elucidate the function of the self-sufficient CYP116B46 fusion enzyme, from the thermophilic bacterium Tepidiphilus thermophilus.

The impact of respiratory infections and probiotic use on the nasal microbiota of frail residents in long-term care homes.

Background: Residents in long-term care homes, who tend to be of advanced age and frail, are at increased risk of respiratory infections. The respiratory microbiota is known to change with age, but whether these changes contribute to the risk of infection is not known. Our goal was to determine how the nasal microbiota of frail older adults changes during symptoms of influenza-like illness (ILI) and how this may be impacted by enrolment in a placebo-controlled trial testing the feasibility of administering a GG probiotic to prevent respiratory infection (2014-2017).

Novel ENT live telehealth and live video-otoscopy clinics in remote Australia: outcomes and comparisons to traditional clinic models.

Background: Coronavirus disease 2019 challenged the delivery of healthcare in Australia, disproportionately impacting vulnerable patients, including Aboriginal and/or Torres Strait Islander peoples and those living in remote regions. The otolaryngology service provided to remote Western Australia adapted to these barriers by altering clinical consultations to a digital model.

Methods: A review was undertaken of patients in regional Western Australia.

Computerized adaptive test strategies for the matrix reasoning subtest of the Wechsler Adult Intelligence Scale, 4th Edition (WAIS-IV).

Objective: Most neuropsychological tests were developed without the benefit of modern psychometric theory. We used item response theory (IRT) methods to determine whether a widely used test - the 26-item Matrix Reasoning subtest of the WAIS-IV - might be used more efficiently if it were administered using computerized adaptive testing (CAT).

Method: Data on the Matrix Reasoning subtest from 2197 participants enrolled in the National Neuropsychology Network (NNN) were analyzed using a two-parameter logistic (2PL) IRT model.

Staphylococcal Periscope proteins Aap, SasG, and Pls project noncanonical legume-like lectin adhesin domains from the bacterial surface.

Staphylococcus aureus and Staphylococcus epidermidis are frequently associated with medical device infections that involve establishment of a bacterial biofilm on the device surface. Staphylococcal surface proteins Aap, SasG, and Pls are members of the Periscope Protein class and have been implicated in biofilm formation and host colonization; they comprise a repetitive region ("B region") and an N-terminal host colonization domain within the "A region," predicted to be a lectin domain. Repetitive E-G5 domains (as found in Aap, SasG, and Pls) form elongated "stalks" that would vary in length with repeat number, resulting in projection of the N-terminal A domain variable distances from the bacterial cell surface.

Efficient -demethylation of lignin monoaromatics using the peroxygenase activity of cytochrome P450 enzymes.

A crucial reaction in harnessing renewable carbon from lignin is -demethylation. We demonstrate the selective -demethylation of syringol and guaiacol using different cytochrome P450 enzymes. These can efficiently use hydrogen peroxide which, when compared to nicotinamide cofactor-dependent monooxygenases and synthetic methods, allows for cheap and clean -demethylation of lignin-derived aromatics.

The long and the short of Periscope Proteins.

Bacteria sense, interact with, and modify their environmental niche by deploying a molecular ensemble at the cell surface. The changeability of this exposed interface, combined with extreme changes in the functional repertoire associated with lifestyle switches from planktonic to adherent and biofilm states necessitate dynamic variability. Dynamic surface changes include chemical modifications to the cell wall; export of diverse extracellular biofilm components; and modulation of expression of cell surface proteins for adhesion, co-aggregation and virulence.

Construct identification in the neuropsychological battery: What are we measuring?

Objective: Major obstacles to data harmonization in neuropsychology include lack of consensus about what constructs and tests are most important and invariant across healthy and clinical populations. This study addressed these challenges using data from the National Neuropsychology Network (NNN).

Method: Data were obtained from 5,000 NNN participants and Pearson standardization samples.

The Effectiveness of a Specialized Primary Care Medical Home for Patients with Serious Mental Illness.

Background: There are unmet primary care needs among people with serious mental illness that might be improved with integrated care and medical care management. Many healthcare organizations have attempted to address this problem, but few interventions have been rigorously studied and found to be effective.

Objective: Study the implementation and effectiveness of a novel, specialized primary care medical home designed to improve the healthcare of patients with serious mental illness.

Model Systems to Study the Chronic, Polymicrobial Infections in Cystic Fibrosis: Current Approaches and Exploring Future Directions.

A recent workshop titled "Developing Models to Study Polymicrobial Infections," sponsored by the Dartmouth Cystic Fibrosis Center (DartCF), explored the development of new models to study the polymicrobial infections associated with the airways of persons with cystic fibrosis (CF). The workshop gathered 35+ investigators over two virtual sessions. Here, we present the findings of this workshop, summarize some of the challenges involved with developing such models, and suggest three frameworks to tackle this complex problem.

Integrating Mental Health in Safety-net Primary Care: A Five-year Observational Study on Visits in a County Health System.

Background: Beginning in 2010, Los Angeles County Departments of Health Services and Mental Health collaborated to increase access to effective mental health care. The Mental Health Integration Program (MHIP) embedded behavioral health specialists in primary care clinics to deliver brief, problem-focused treatments, and psychiatric consultation support for primary care-prescribed psychotropic medications.

Objective: The aim was to compare primary care visits associated with psychiatric diagnoses before and after MHIP implementation.

Periscope Proteins are variable-length regulators of bacterial cell surface interactions.

Changes at the cell surface enable bacteria to survive in dynamic environments, such as diverse niches of the human host. Here, we reveal "Periscope Proteins" as a widespread mechanism of bacterial surface alteration mediated through protein length variation. Tandem arrays of highly similar folded domains can form an elongated rod-like structure; thus, variation in the number of domains determines how far an N-terminal host ligand binding domain projects from the cell surface.

Evidence for Selection in the Abundant Accessory Gene Content of a Prokaryote Pangenome.

A pangenome is the complete set of genes (core and accessory) present in a phylogenetic clade. We hypothesize that a pangenome's accessory gene content is structured and maintained by selection. To test this hypothesis, we interrogated the genomes of 40 Pseudomonas species for statistically significant coincident (i.

Rationale and Design of the National Neuropsychology Network.

Objective: The National Neuropsychology Network (NNN) is a multicenter clinical research initiative funded by the National Institute of Mental Health (NIMH; R01 MH118514) to facilitate neuropsychology's transition to contemporary psychometric assessment methods with resultant improvement in test validation and assessment efficiency.

Method: The NNN includes four clinical research sites (Emory University; Medical College of Wisconsin; University of California, Los Angeles (UCLA); University of Florida) and Pearson Clinical Assessment. Pearson Q-interactive (Q-i) is used for data capture for Pearson published tests; web-based data capture tools programmed by UCLA, which serves as the Coordinating Center, are employed for remaining measures.

A Multisite Randomized Controlled Trial Comparing the Effects of Intervention Intensity and Intervention Style on Outcomes for Young Children With Autism.

Objective: This randomized, multisite, intent-to-treat study tested the effects of 2 levels of treatment intensity (number of hours) and 2 treatment styles on the progress of young children with autism spectrum disorder (ASD). We predicted that initial severity of developmental delay or autism symptoms would moderate the effects of intensity and style on progress in 4 domains: autism symptom severity, expressive communication, receptive language, and nonverbal ability.

Method: A total of 87 children with ASD, mean age 23.

Horizontal Gene Transfer as a Source of Conflict and Cooperation in Prokaryotes.

Horizontal gene transfer (HGT) is one of the most important processes in prokaryote evolution. The sharing of DNA can spread neutral or beneficial genes, as well as genetic parasites across populations and communities, creating a large proportion of the variability acted on by natural selection. Here, we highlight the role of HGT in enhancing the opportunities for conflict and cooperation within and between prokaryote genomes.

Rational Design and Self-Assembly of Coiled-Coil Linked SasG Protein Fibrils.

Protein engineering is an attractive approach for the self-assembly of nanometer-scale architectures for a range of potential nanotechnologies. Using the versatile chemistry provided by protein folding and assembly, coupled with amino acid side-chain functionality, allows for the construction of precise molecular "protein origami" hierarchical patterned structures for a range of nanoapplications such as stand-alone enzymatic pathways and molecular machines. The surface protein SasG is a rigid, rod-like structure shown to have high mechanical strength due to "clamp-like" intradomain features and a stabilizing interface between the G5 and E domains, making it an excellent building block for molecular self-assembly.

Coinfinder: detecting significant associations and dissociations in pangenomes.

The accessory genes of prokaryote and eukaryote pangenomes accumulate by horizontal gene transfer, differential gene loss, and the effects of selection and drift. We have developed Coinfinder, a software program that assesses whether sets of homologous genes (gene families) in pangenomes associate or dissociate with each other (i.e.

Culture-enriched metagenomic sequencing enables in-depth profiling of the cystic fibrosis lung microbiota.

Amplicon sequencing (for example, of the 16S rRNA gene) identifies the presence and relative abundance of microbial community members. However, metagenomic sequencing is needed to identify the genetic content and functional potential of a community. Metagenomics is challenging in samples dominated by host DNA, such as those from the skin, tissue and respiratory tract.

Defining the remarkable structural malleability of a bacterial surface protein Rib domain implicated in infection.

groups A and B cause serious infections, including early onset sepsis and meningitis in newborns. Rib domain-containing surface proteins are found associated with invasive strains and elicit protective immunity in animal models. Yet, despite their apparent importance in infection, the structure of the Rib domain was previously unknown.

Mobile Phone and Smartphone Use by People With Serious Mental Illness.

Objective: Mobile technologies, such as smartphones, can improve health services by delivering assessments and interventions that reach people in their daily lives. There is, however, disagreement regarding whether people with serious mental illness make meaningful use of mobile technology and whether interventions that rely on mobile technology should be tailored for this population.

Methods: At two clinics, 249 people with serious mental illness were interviewed regarding mobile phone use, and their cognitive functioning was assessed.

A Multisite Randomized Controlled Two-Phase Trial of the Early Start Denver Model Compared to Treatment as Usual.

Objective: This single-blind, randomized, multisite, intent-to-treat study was designed to replicate and extend Dawson et al.'s (Pediatrics. 2010;125: e17-e23) randomized controlled trial testing the effects of the Early Start Denver Model (ESDM), an intensive play- and routines-based intervention delivered in natural settings.

Implementing Patient-Reported Outcomes to Improve the Quality of Care for Weight of Patients with Schizophrenia.

"Enhancing QUality of Care In Psychosis" (EQUIP) was an eight-site clustered controlled trial of the implementation and effectiveness of patient-reported outcomes to support evidence-based practice and improve care for schizophrenia. Implementation sites chose to improve care for weight. Implementation included monitoring patient-reported outcomes using kiosks, patient and staff education, quality improvement teams, and phone care management.