The Methylome of Motile Cilia.

Cilia are highly complex motile, sensory, and secretory organelles that contain perhaps 1,000 or more distinct protein components, many of which are subject to various post-translational modifications such as phosphorylation, N-terminal acetylation, and proteolytic processing. Another common modification is the addition of one or more methyl groups to the side chains of arginine and lysine residues. These tunable additions delocalize the side-chain charge, decrease hydrogen bond capacity, and increase both bulk and hydrophobicity. Methylation is usually mediated by S-adenosylmethionine (SAM)-dependent methyltransferases and reversed by demethylases. Previous studies have identified several ciliary proteins that are subject to methylation including axonemal dynein heavy chains that are modified by a cytosolic methyltransferase. Here we have performed an extensive proteomic analysis of multiple independently derived cilia samples to assess the potential for SAM metabolism and the extent of methylation in these organelles. We find that cilia contain all the enzymes needed for generation of the SAM methyl donor and recycling of the S-adenosylhomocysteine and tetrahydrofolate byproducts. In addition, we find that at least one hundred and fifty-five distinct ciliary proteins are methylated, in some cases at multiple sites. These data provide a comprehensive resource for studying the consequences of methyl marks on ciliary biology.

The Nanoscale Structure and Stability of Organic Photovoltaic Blends Processed with Solvent Additives.

Controlling the nanomorphology in bulk heterojunction photoactive blends is crucial for optimizing the performance and stability of organic photovoltaic (OPV) technologies. A promising approach is to alter the drying dynamics and consequently, the nanostructure of the blend film using solvent additives such as 1,8-diiodooctane (DIO). Although this approach is demonstrated extensively for OPV systems incorporating fullerene-based acceptors, it is unclear how solvent additive processing influences the morphology and stability of nonfullerene acceptor (NFA) systems. Here, small angle neutron scattering (SANS) is used to probe the nanomorphology of two model OPV systems processed with DIO: a fullerene-based system (PBDB-T:PC71BM) and an NFA-based system (PBDB-T:ITIC). To overcome the low intrinsic neutron scattering length density contrast in polymer:NFA blend films, the synthesis of a deuterated NFA analog (ITIC-d52) is reported. Using SANS, new insights into the nanoscale evolution of fullerene and NFA-based systems are provided by characterizing films immediately after fabrication, after thermal annealing, and after aging for 1 year. It is found that DIO processing influences fullerene and NFA-based systems differently with NFA-based systems characterized by more phase-separated domains. After long-term aging, SANS reveals both systems demonstrate some level of thermodynamic induced domain coarsening.

Feasibility of precision smoking treatment in a low-income community setting: results of a pilot randomized controlled trial in The Southern Community Cohort Study.

BACKGROUND: The feasibility of precision smoking treatment in socioeconomically disadvantaged communities has not been studied. METHODS: Participants in the Southern Community Cohort Study who smoked daily were invited to join a pilot randomized controlled trial of three smoking cessation interventions: guideline-based care (GBC), GBC plus nicotine metabolism-informed care (MIC), and GBC plus counseling guided by a polygenic risk score (PRS) for lung cancer. Feasibility was assessed by rates of study enrollment, engagement, and retention, targeting > 70% for each. Using logistic regression, we also assessed whether feasibility varied by age, sex, race, income, education, and attitudes toward precision smoking treatment. RESULTS: Of 92 eligible individuals (79.3% Black; 68.2% with household income < $15,000), 67 (72.8%; 95% CI 63.0-80.9%) enrolled and were randomized. Of these, 58 (86.6%; 95% CI 76.4-92.8%) engaged with the intervention, and of these engaged participants, 43 (74.1%; 95% CI 61.6-83.7%) were retained at 6-month follow-up. Conditional on enrollment, older age was associated with lower engagement (OR 0.83, 95% CI 0.73-0.95, p = 0.008). Conditional on engagement, retention was significantly lower in the PRS arm than in the GBC arm (OR 0.18, 95% CI 0.03-1.00, p = 0.050). No other selection effects were observed. CONCLUSIONS: Genetically informed precision smoking cessation interventions are feasible in socioeconomically disadvantaged communities, exhibiting high enrollment, engagement, and retention irrespective of race, sex, income, education, or attitudes toward precision smoking treatment. Future smoking cessation interventions in this population should take steps to engage older people and to sustain participation in interventions that include genetic risk counseling. TRIAL REGISTRATION: ClinicalTrials.gov No. NCT03521141, Registered 27 April 2018, https://www. CLINICALTRIALS: gov/study/NCT03521141.

Loneliness among homeless-experienced older adults with cognitive or functional impairments: qualitative findings from the HOPE HOME study.

BACKGROUND: Loneliness is more common in older adults and those who face structural vulnerabilities, including homelessness. The homeless population is aging in the United States; now, 48% of single homeless adults are 50 and older. We know little about loneliness among older adults who have experienced homelessness. We aimed to describe the loneliness experience among homeless-experienced older adults with cognitive and functional impairments and the individual, social, and structural conditions that shaped these loneliness experiences. METHODS: We purposively sampled 22 older adults from the HOPE HOME study, a longitudinal cohort study among adults aged 50 years or older experiencing homelessness in Oakland, California. We conducted in-depth interviews about participants perceived social support and social isolation. We conducted qualitative content analysis. RESULTS: Twenty participants discussed loneliness experience, who had a median age of 57 and were mostly Black (80%) and men (65%). We developed a typology of participants' loneliness experience and explored the individual, social, and structural conditions under which each loneliness experience occurred. We categorized the loneliness experience into four groups: (1) "lonely- distressed", characterized by physical impairment and severe isolation; (2) "lonely- rather be isolated", reflecting deliberate social isolation as a result of trauma, marginalization and aging-related resignation; (3) "lonely- transient", as a result of aging, acceptance and grieving; and (4) "not lonely"- characterized by stability and connection despite having experienced homelessness. CONCLUSIONS: Loneliness is a complex and heterogenous social phenomenon, with homeless-experienced older adults with cognitive or functional impairments exhibiting diverse loneliness experiences based on their individual life circumstances and needs. While the most distressing loneliness experience occurred among those with physical impairment and mobility challenges, social and structural factors such as interpersonal and structural violence during homelessness shaped these experiences.

Cilia Provide a Platform for the Generation, Regulated Secretion, and Reception of Peptidergic Signals.

Cilia are microtubule-based cellular projections that act as motile, sensory, and secretory organelles. These structures receive information from the environment and transmit downstream signals to the cell body. Cilia also release vesicular ectosomes that bud from the ciliary membrane and carry an array of bioactive enzymes and peptide products. Peptidergic signals represent an ancient mode of intercellular communication, and in metazoans are involved in the maintenance of cellular homeostasis and various other physiological processes and responses. Numerous peptide receptors, subtilisin-like proteases, the peptide-amidating enzyme, and bioactive amidated peptide products have been localized to these organelles. In this review, we detail how cilia serve as specialized signaling organelles and act as a platform for the regulated processing and secretion of peptidergic signals. We especially focus on the processing and trafficking pathways by which a peptide precursor from the green alga Chlamydomonas reinhardtii is converted into an amidated bioactive product-a chemotactic modulator-and released from cilia in ectosomes. Biochemical dissection of this complex ciliary secretory pathway provides a paradigm for understanding cilia-based peptidergic signaling in mammals and other eukaryotes.

Combination of a pH-responsive peptide amphiphile and a conventional antibiotic in treating Gram-negative bacteria.

BACKGROUND: Clinical treatments ofgastric infections using antibiotics suffer from the undesired killing of commensal bacteria and emergence of antibiotic resistance. It is desirable to develop pH-responsive antimicrobial peptides (AMPs) that kill pathogenic bacteria such as H. pyloriand resistant E. coli under acidic environment with minimal impact to commensal bacteria whilst not causing antibiotic resistance. EXPERIMENTS: Using a combined approach of cell assays, molecular dynamics (MD) simulations and membrane models facilitating biophysical and biochemical measurements including small angle neutron scattering (SANS), we have characterized the pH-responsive physiochemical properties and antimicrobial performance of two amphiphilic AMPs, GIIKDIIKDIIKDI-NH2 and GIIKKIIDDIIKKI-NH2 (denoted as 3D and 2D, respectively), that were designed by selective substitutions of cationic residues of Lys (K) in the extensively studied AMP G(IIKK)3I-NH2 with anionic residue Asp (D). FINDINGS: Whilst 2D kept non-ordered coils across the entire pH range studied, 3D displayed a range of secondary structures when pH was shifted from basic to acidic, with distinct self-assembly into nanofibers in aqueous environment. Further experimental and modeling studies revealed that the AMPs interacted differently with the inner and outer membranes of Gram-negative bacteria in a pH-responsive manner and that the structural features characterized by membrane leakage and intramembrane nanoaggregates revealed from fluorescence spectroscopy and SANS were well linked to antimicrobial actions. Different antimicrobial efficacies of 2D and 3D were underlined by the interplay between their ability to bind to the outer membrane lipid LPS (lipopolysaccharide), outer membrane permeability change and inner membrane depolarization and leakage. Furthermore, AMP's binding with the inner membrane under acidic condition caused both the dissipation of membrane potential (Δψ) and the continuous dissipation of transmembrane ΔpH, with Δψ and ΔpH being the key components of the proton motive force. Combinations of antibiotic (Minocycline) with the pH-responsive AMP generated the synergistic effects against Gram-negative bacteria only under acidic condition. These features are crucial to target applications to gastric infections, anti-acne and wound healing.

The ATCC genome portal: 3,938 authenticated microbial reference genomes.

The ATCC Genome Portal (AGP, https://genomes.atcc.org/) is a database of authenticated genomes for bacteria, fungi, protists, and viruses held in ATCC's biorepository. It now includes 3,938 assemblies (253% increase) produced under ISO 9000 by ATCC. Here, we present new features and content added to the AGP for the research community.

Methylation of ciliary dynein motors involves the essential cytosolic assembly factor DNAAF3/PF22.

Axonemal dynein motors drive ciliary motility and can consist of up to twenty distinct components with a combined mass of ~2 MDa. In mammals, failure of dyneins to assemble within the axonemal superstructure leads to primary ciliary dyskinesia. Syndromic phenotypes include infertility, rhinitis, severe bronchial conditions, and situs inversus. Nineteen specific cytosolic factors (Dynein Axonemal Assembly Factors; DNAAFs) are necessary for axonemal dynein assembly, although the detailed mechanisms involved remain very unclear. Here, we identify the essential assembly factor DNAAF3 as a structural ortholog of S-adenosylmethionine-dependent methyltransferases. We demonstrate that dynein heavy chains, especially those forming the ciliary outer arms, are methylated on key residues within various nucleotide-binding sites and on microtubule-binding domain helices directly involved in the transition to low binding affinity. These variable modifications, which are generally missing in a Chlamydomonas null mutant for the DNAAF3 ortholog PF22 (DAB1), likely impact on motor mechanochemistry fine-tuning the activities of individual dynein complexes.

Controlling 1D Nanostructures and Handedness by Polar Residue Chirality of Amphiphilic Peptides.

Peptide assemblies are promising nanomaterials, with their properties and technological applications being highly hinged on their supramolecular architectures. Here, how changing the chirality of the terminal charged residues of an amphiphilic hexapeptide sequence Ac-I4 K2 -NH2 gives rise to distinct nanostructures and supramolecular handedness is reported. Microscopic imaging and neutron scattering measurements show thin nanofibrils, thick nanofibrils, and wide nanotubes self-assembled from four stereoisomers. Spectroscopic and solid-state nuclear magnetic resonance (NMR) analyses reveal that these isomeric peptides adopt similar anti-parallel ß-sheet secondary structures. Further theoretical calculations demonstrate that the chiral alterations of the two C-terminal lysine residues cause the formation of diverse single ß-strand conformations, and the final self-assembled nanostructures and handedness are determined by the twisting direction and degree of single ß-strands. This work not only lays a useful foundation for the fabrication of diverse peptide nanostructures by manipulating the chirality of specific residues but also provides a framework for predicting the supramolecular structures and handedness of peptide assemblies from single molecule conformations.

Loneliness among older adults who have experienced homelessness: qualitative findings from the HOPE HOME study.

Background: Loneliness is more common in older adults and those who face structural vulnerabilities, including homelessness. The homeless population is aging. We know little about loneliness among older adults who have experienced homelessness. We aimed to describe the loneliness experience among older adults who have experienced homelessness and the individual, social, and structural conditions that shaped these loneliness experiences. Methods: We purposively sampled 22 older adults from the HOPE HOME study, a longitudinal cohort study among adults aged 50 years or older experiencing homelessness in Oakland, California. We conducted in-depth interviews about participants' perceived social support and social isolation. We conducted qualitative content analysis. Results: Twenty participants discussed loneliness experience, who had a median age of 57 and were mostly Black (80%) and men (65%). We developed a typology of participants' loneliness experience and explored the individual, social, and structural conditions under which each loneliness experience occurred. We categorized the loneliness experience into four groups: 1) "lonely - distressed", characterized by physical impairment and severe isolation; 2) "lonely - rather be isolated", reflecting deliberate social isolation as a result of trauma, marginalization and aging-related resignation; 3) "lonely - transient", as a result of aging, acceptance and grieving; and 4) "not lonely" - characterized by stability and connection despite having experienced homelessness. Conclusions: Loneliness is a complex and heterogenous social phenomenon, with older adults who have experienced homelessness exhibiting diverse loneliness experiences based on their individual life circumstances and needs. While the most distressing loneliness experience occurred among those with physical impairment and mobility challenges, social and structural factors such as interpersonal and structural violence during homelessness shaped these experiences.

N-Terminal Processing and Modification of Ciliary Dyneins.

Axonemal dyneins are highly complex microtubule motors that power ciliary motility. These multi-subunit enzymes are assembled at dedicated sites within the cytoplasm. At least nineteen cytosolic factors are specifically needed to generate dynein holoenzymes and/or for their trafficking to the growing cilium. Many proteins are subject to N-terminal processing and acetylation, which can generate degrons subject to the AcN-end rule, alter N-terminal electrostatics, generate new binding interfaces, and affect subunit stoichiometry through targeted degradation. Here, we have used mass spectrometry of cilia samples and electrophoretically purified dynein heavy chains from Chlamydomonas to define their N-terminal processing; we also detail the N-terminal acetylase complexes present in this organism. We identify four classes of dynein heavy chain based on their processing pathways by two distinct acetylases, one of which is dependent on methionine aminopeptidase activity. In addition, we find that one component of both the outer dynein arm intermediate/light chain subcomplex and the docking complex is processed to yield an unmodified Pro residue, which may provide a setpoint to direct the cytosolic stoichiometry of other dynein complex subunits that contain N-terminal degrons. Thus, we identify and describe an additional level of processing and complexity in the pathways leading to axonemal dynein formation in cytoplasm.

Inherently disordered regions of axonemal dynein assembly factors.

The dynein-driven beating of cilia is required to move individual cells and to generate fluid flow across surfaces and within cavities. These motor enzymes are highly complex and can contain upwards of 20 different protein components with a total mass approaching 2 MDa. The dynein heavy chains are enormous proteins consisting of ~4500 residues and ribosomes take approximately 15 min to synthesize one. Studies in a broad array of organisms ranging from the green alga Chlamydomonas to humans has identified 19 cytosolic factors (DNAAFs) that are needed to specifically build axonemal dyneins; defects in many of these proteins lead to primary ciliary dyskinesia in mammals which can result in infertility, severe bronchial problems, and situs inversus. How all these factors cooperate in a spatially and temporally regulated manner to promote dynein assembly in cytoplasm remains very uncertain. These DNAAFs contain a variety of well-folded domains many of which provide protein interaction surfaces. However, many also exhibit large regions that are predicted to be inherently disordered. Here I discuss the nature of these unstructured segments, their predicted propensity for driving protein phase separation, and their potential for adopting more defined conformations during the dynein assembly process.

Outer-arm dynein light chain LC1 is required for normal motor assembly kinetics, ciliary stability, and motility.

Light chain 1 (LC1) is a highly conserved leucine-rich repeat protein associated with the microtubule-binding domain of the Chlamydomonas outer-dynein arm γ heavy chain. LC1 mutations in humans and trypanosomes lead to motility defects, while its loss in oomycetes results in aciliate zoospores. Here we describe a Chlamydomonas LC1 null mutant (dlu1-1). This strain has reduced swimming velocity and beat frequency, can undergo waveform conversion, but often exhibits loss of hydrodynamic coupling between the cilia. Following deciliation, Chlamydomonas cells rapidly rebuild cytoplasmic stocks of axonemal dyneins. Loss of LC1 disrupts the kinetics of this cytoplasmic preassembly so that most outer-arm dynein heavy chains remain monomeric even after several hours. This suggests that association of LC1 with its heavy chain-binding site is a key step or checkpoint in the outer-arm dynein assembly process. Similarly to strains lacking the entire outer arm and inner arm I1/f, we found that loss of LC1 and I1/f in dlu1-1 ida1 double mutants resulted in cells unable to build cilia under normal conditions. Furthermore, dlu1-1 cells do not exhibit the usual ciliary extension in response to lithium treatment. Together, these observations suggest that LC1 plays an important role in the maintenance of axonemal stability.

Can Treatment Support Mitigate Nicotine Metabolism-Based Disparities in Smoking Abstinence? Secondary Analysis of the Helping HAND 4 Trial.

INTRODUCTION: The nicotine metabolite ratio (NMR), a biomarker of CYP2A6-mediated nicotine metabolism, predicts the efficacy of nicotine replacement therapy (NRT), with fast metabolizers benefiting less than slow metabolizers. Whether treatment support to optimize NRT use (henceforth "treatment support") modifies this pharmacogenetic relationship is unknown. METHODS: Hospitalized adult daily smokers were assigned to one of two post-discharge smoking cessation interventions offering NRT and counseling: (1) Transitional Tobacco Care Management, which delivered enhanced treatment support via free combination NRT at discharge and automated counseling, and (2) a quitline-based approach representing usual care (UC). The primary outcome was biochemically verified 7-day point prevalence abstinence 6 months after discharge. Secondary outcomes were the use of NRT and counseling during the 3-month intervention period. Logistic regression models tested for interactions between NMR and intervention, controlling for sex, race, alcohol use, and BMI. RESULTS: Participants (N = 321) were classified as slow (n = 80) or fast (n = 241) metabolizers relative to the first quartile of NMR (0.012-0.219 vs. 0.221-3.455, respectively). Under UC, fast (vs. slow) metabolizers had lower odds of abstinence at 6 months (aOR 0.35, 95% CI 0.13-0.95) and similar odds of NRT and counseling use. Compared to UC, enhanced treatment support increased abstinence (aOR 2.13, 95% CI 0.98-4.64) and use of combination NRT (aOR 4.62, 95% CI 2.57-8.31) in fast metabolizers, while reducing abstinence in slow metabolizers (aOR 0.21, 95% CI 0.05-0.87; NMR-by-intervention interaction p = .004). CONCLUSIONS: Treatment support increased abstinence and optimal use of NRT among fast nicotine metabolizers, thereby mitigating the gap in abstinence between fast and slow metabolizers. IMPLICATIONS: In this secondary analysis of two smoking cessation interventions for recently hospitalized smokers, fast nicotine metabolizers quit at lower rates than slow metabolizers, but providing fast metabolizers with enhanced treatment support doubled the odds of quitting in this group and mitigated the disparity in abstinence between fast and slow metabolizers. If validated, these findings could lead to personalized approaches to smoking cessation treatment that improve outcomes by targeting treatment support to those who need it most.

Isolation of ciliary ectosomes and analysis of amidated peptide-mediated chemotaxis in Chlamydomonas.

Ciliary ectosomes are vesicles that bud from the ciliary membrane. Isolation and analysis of these structures can shed light on their bioactive cargoes and identify proteins and biomolecules involved in intercellular communication and various physiological processes. Most published methods to isolate ciliary ectosomes are based on their size (100nm to 1µm) to separate cilia-derived vesicles from isolated cilia and/or intact cells. However, it is often difficult to determine the origin of extracellular vesicles and to distinguish ciliary ectosomes from ectosomes budded from the plasma membrane or from exosomes that derive from multivesicular bodies. Here, we describe procedures to isolate and purify ciliary ectosomes from the unicellular green alga, Chlamydomonas reinhardtii, through differential and iodixanol density gradient ultracentrifugation; in this organism, the ciliary membrane is the only membrane directly exposed to the environment and thus ectosomes are of known origin. Ciliary ectosomes contain enzymes and α-amidated peptide products required to mediate peptidergic-signaling cascades; one identified amidated peptide acts as a chemotactic modulator for C. reinhardtii gametes. Classical methods used to assess chemotaxis do not provide quantitative measurements of the chemotactic gradient or the real-time effects on the migration of fast moving cells. Consequently, we developed a chemotaxis assay protocol using microfluidic channel slides that provides quantitative and qualitative measurements of the chemotactic gradient and cell migration. Here, we describe how to establish a stable gradient of a bioactive substance in microfluidic channel slides and perform quantitative assays to assess chemotaxis of both individual cells and populations of C. reinhardtii.

Working Together to Find a Voice: Recommendations for Voice Healthcare Based on Expert-By-Experience and Practitioner Consensus.

OBJECTIVES: Voice care services aim to provide effective and meaningful voice care. Current practice guidance recommends a multidisciplinary voice care approach, supported by the evidence-base and practitioner experience. However, unlike other areas of physical and mental health, current voice care guidance does not explicitly include the voices of experts-by-experience, meaning those who have lived experience of voice difficulties. The perspectives of those working within nonclinical voice professions, such as vocal coaches, are also often omitted. There is therefore a need for updated practice guidance which prioritizes expert-by-experience and nonclinical perspectives. METHODS: Vocal Health Education hosted a consensus meeting in London, UK. The meeting was coproduced with experts-by-experience, and attendees included those with lived experience of voice difficulties and practitioners across a range of disciplines within voice care. The content of the meeting was synthesized into themes and associated recommendations were drafted and agreed to by all attendees. RESULTS: The consensus statement offers practical advice to those working in voice care. Recommendations are offered for multidisciplinary and biopsychosocial voice care, with a focus on person-centered practice and the valuing of lived experience. Through discussion, consensus was reached regarding recommendations for voice care assessment and treatment, practitioner approach, psychosocial considerations, and service design. The need for greater expert-by-experience involvement, coproduction, and co-construction was emphasized throughout. CONCLUSIONS: This report emphasizes the voices of those with lived experience. It highlights ways of updating or improving current care, with the aim of informing clinical practice as well as research and service development. The consensus statement is the first in voice care to include experts-by-experience at the center of its recommendations, underlining the need for more coproduced and co-constructed research and practice within voice healthcare.

Cholesterol in the cargo membrane amplifies tau inhibition of kinesin-1-based transport.

Intracellular cargos are often membrane-enclosed and transported by microtubule-based motors in the presence of microtubule-associated proteins (MAPs). Whereas increasing evidence reveals how MAPs impact the interactions between motors and microtubules, critical questions remain about the impact of the cargo membrane on transport. Here we combined in vitro optical trapping with theoretical approaches to determine the effect of a lipid cargo membrane on kinesin-based transport in the presence of MAP tau. Our results demonstrate that attaching kinesin to a fluid lipid membrane reduces the inhibitory effect of tau on kinesin. Moreover, adding cholesterol, which reduces kinesin diffusion in the cargo membrane, amplifies the inhibitory effect of tau on kinesin binding in a dosage-dependent manner. We propose that reduction of kinesin diffusion in the cargo membrane underlies the effect of cholesterol on kinesin binding in the presence of tau, and we provide a simple model for this proposed mechanism. Our study establishes a direct link between cargo membrane cholesterol and MAP-based regulation of kinesin-1. The cholesterol effects uncovered here may more broadly extend to other lipid alterations that impact motor diffusion in the cargo membrane, including those associated with aging and neurological diseases.

Peptide Self-Assemblies from Unusual α-Sheet Conformations Based on Alternation of d/l Amino Acids.

Peptide self-assembly is a hierarchical process during which secondary structures formed in the initial stages play a critical role in determining the subsequent assembling processes and final structural ordering. Unusual secondary structures hold promise as a source to develop novel supramolecular architectures with unique properties. In this work, we report the design of a new peptide self-assembly strategy based on unusual α-sheet secondary structures. In light of the strong propensity of leucine toward forming helical conformations and its high hydrophobicity, we design two short amphiphilic peptides Ac-LDLLDLK-NH2 and Ac-DLLDLLDK-NH2 with alternating l- and d-form amino acids. Microscopic imaging, neutron scattering, and spectroscopic measurements indicate that the two heterochiral peptides form highly ordered wide nanotubes and helical ribbons with monolayer thickness, in sharp contrast to twisted nanofibrils formed by the homochiral peptide Ac-LLLLK-NH2. Molecular dynamics simulations from monomers to trimers reveal that the two heteropeptides fold into α-sheets instead of ß-sheets, which readily pack into tubular architectures in oligomer simulations. Simulated circular dichroism spectra based on α-sheet oligomers validate the proposed α-sheet secondary structures. These results form an important basis for the rational design of higher-order peptide assemblies with novel properties based on unusual α-sheet secondary structures.

Neurocognitive health of older adults experiencing homelessness in Oakland, California.

Background and objectives: The homeless population in the US is aging. Cognitive impairment is prevalent in this population, yet little is known about the neurologic etiologies of such impairment. Addressing this gap in knowledge is important because homeless older adults with cognitive impairment due to neurodegenerative disease may need lifelong tailored support to obtain and maintain housing. In this study, we characterized the neurocognitive health of a sample of adults who experienced homelessness for the first time after age 50 using gold standard behavioral neurology examination practices. Methods: We conducted a descriptive cross-sectional study of older adults who first experienced homelessness after age 50. We recruited our sample purposively from an ongoing longitudinal cohort study of adults who were aged 50 and over and homeless when they entered the cohort. For this sub study, we enrolled a convenience sample from those who reported their first episode of homelessness after age 50. We did not exclude individuals based on history of substance use. Neurologists conducted a structured neurocognitive history intake, neurological examination, neuropsychological evaluation, and functional assessment between November 2020 and February 2021. We screened all participants for neurocognitive disorders using gold standard clinical research diagnostic criteria. Results: We evaluated 25 participants, most were men (76%) and Black (84%), with a median age of 61 years. The most common neurocognitive complaints included deficits in recent episodic memory (n = 15, 60%), executive functions (n = 13, 52%), and behavior/mood, with apathy being the most common complaint (n = 20, 80%). Neuropsychological testing revealed a high prevalence of socioemotional deficits (n = 20, 80%). Common neurological examination deficits included difficulties with coordination, such as impaired Luria task (n = 16, 64%), signs of distal peripheral neuropathy (n = 8, 32%), anosmia/hyposmia (n = 4, 21%), and signs of mild Parkinsonism (n = 5, 20%). The most common diagnoses were MCI (n = 7, 28%), bvFTD (n = 4, 16%), AD (n = 4, 16%), and DLB (n = 2, 8%). Discussion: Our findings suggest that neurocognitive concerns and examination deficits are common among older homeless adults. Specific neurocognitive disorders may be overrepresented in this population, particularly frontotemporal disorders. Longitudinal studies involving brain biomarkers are needed to characterize the neurocognitive health of this vulnerable population more precisely.