Is Collective Efficacy Age Graded? The Development and Evaluation of a New Measure of Collective Efficacy for Older Adults

Objectives. Community processes are key determinants of older adults' ability to age in place, but existing scales measuring these constructs may not provide accurate, unbiased measurements among older adults because they were designed with the concerns of child-rearing respondents in mind. This study examines the properties of a new theory-based measure of collective efficacy (CE) that accounts for the perspectives of older residents. Methods. Data come from the population-based Chicago Neighborhood Organization, Aging and Health study (N = 1,151), which surveyed adults aged 65 to 95. Using descriptive statistics, correlations, and factor analysis, we explored the acceptability, reliability, and validity of the new measure. Results. Principal component analysis indicated that the new scale measures a single latent factor. It had good internal consistency reliability, was highly correlated with the original scale, and was similarly associated with neighborhood exchange and disorder, self-rated health, mobility, and loneliness. The new scale also showed less age-differentiated nonresponse compared to the original scale. Discussion. The older adult CE scale has reliability and validity equivalent to that of the existing measure but benefits from a more developed theoretical grounding and reduced likelihood of age-related differential nonresponse

msmsEval: tandem mass spectral quality assignment for high-throughput proteomics

BACKGROUND: In proteomics experiments, database-search programs are the method of choice for protein identification from tandem mass spectra. As amino acid sequence databases grow however, computing resources required for these programs have become prohibitive, particularly in searches for modified proteins. Recently, methods to limit the number of spectra to be searched based on spectral quality have been proposed by different research groups, but rankings of spectral quality have thus far been based on arbitrary cut-off values. In this work, we develop a more readily interpretable spectral quality statistic by providing probability values for the likelihood that spectra will be identifiable. RESULTS: We describe an application, msmsEval, that builds on previous work by statistically modeling the spectral quality discriminant function using a Gaussian mixture model. This allows a researcher to filter spectra based on the probability that a spectrum will ultimately be identified by database searching. We show that spectra that are predicted by msmsEval to be of high quality, yet remain unidentified in standard database searches, are candidates for more intensive search strategies. Using a well studied public dataset we also show that a high proportion (83.9%) of the spectra predicted by msmsEval to be of high quality but that elude standard search strategies, are in fact interpretable. CONCLUSION: msmsEval will be useful for high-throughput proteomics projects and is freely available for download from . Supports Windows, Mac OS X and Linux/Unix operating systems

Probing vortex-shedding at high frequencies in flows past confined microfluidic cylinders using high-speed microscale particle image velocimetry

Vortex-shedding from micropins has the potential to significantly enhance and intensify scalar transport in microchannels, for example by improving species mixing. However, the onset of vortex-shedding and the mixing efficiency are highly sensitive to the confinement imposed by the microchannel walls. In this work, the time dependent flow past a cylindrical pin in microchannels with different levels of confinement was studied experimentally. The onset of vortex-shedding in such flows is associated with high, kilohertz range frequencies that are difficult to resolve using conventional laser-based microscale particle image velocimetry (μPIV) techniques. Hence, in this study, a high-speed μPIV technique was implemented in order to obtain time-resolved measurements of the velocity fields downstream of the micropin to estimate the corresponding vortex-shedding frequencies and quantify the mixing in the pin wake. The vertical confinement (pin length to diameter ratio) was found to delay the onset of vortex-shedding. When vortex-shedding was present, the shedding frequency and the corresponding Strouhal numbers were found to be greater in channels with higher lateral confinement for the same Reynolds number. Finite-time Lyapunov exponent analysis was performed on the acquired velocity fields to estimate the mixing performance. The results clearly illustrated the significant enhancement in both the mixing in the wake and the mass flux across the centerline of the wake induced by vortex-sheddin

Invadolysin, a conserved lipid-droplet-associated metalloproteinase, is required for mitochondrial function in Drosophila

Mitochondria are the main producers of ATP, the principal energy source of the cell, and reactive oxygen species (ROS), important signaling molecules. Mitochondrial morphogenesis and function depend on a hierarchical network of mechanisms in which proteases appear to be center stage. The invadolysin gene encodes an essential conserved metalloproteinase of the M8 family that is necessary for mitosis and cell migration during Drosophila development. We previously demonstrated that invadolysin is found associated with lipid droplets in cells. Here, we present data demonstrating that invadolysin interacts physically with three mitochondrial ATP synthase subunits. Our studies have focused on the genetic phenotypes of invadolysin and bellwether, the Drosophila homolog of ATP synthase a, mutants. The invadolysin mutation presents defects in mitochondrial physiology similar to those observed in bellwether mutants. The invadolysin and bellwether mutants have parallel phenotypes that affect lipid storage and mitochondrial electron transport chain activity, which result in a reduction in ATP production and an accumulation of ROS. As a consequence, invadolysin mutant larvae show lower energetic status and higher oxidative stress. Our data demonstrate an essential role for invadolysin in mitochondrial function that is crucial for normal development and survival.peer-reviewe

Proteomics Strategy for Identifying Candidate Bioactive Proteins in Complex Mixtures: Application to the Platelet Releasate

Proteomic approaches have proven powerful at identifying large numbers of proteins, but there are fewer reports of functional characterization of proteins in biological tissues. Here, we describe an experimental approach that fractionates proteins released from human platelets, linking bioassay activity to identity. We used consecutive orthogonal separation platforms to ensure sensitive detection: (a) ion-exchange of intact proteins, (b) SDS-PAGE separation of ion-exchange fractions and (c) HPLC separation of tryptic digests coupled to electrospray tandem mass spectrometry. Migration of THP-1 monocytes in response to complete or fractionated platelet releasate was assessed and located to just one of the forty-nine ion-exchange fractions. Over 300 proteins were identified in the releasate, with a wide range of annotated biophysical and biochemical properties, in particular platelet activation, adhesion, and wound healing. The presence of PEDF and involucrin, two proteins not previously reported in platelet releasate, was confirmed by western blotting. Proteins identified within the fraction with monocyte promigratory activity and not in other inactive fractions included vimentin, PEDF, and TIMP-1. We conclude that this analytical platform is effective for the characterization of complex bioactive samples

A boarding school outbreak of pertussis in adolescents : value of laboratory diagnostic methods

Culture for Bordetella pertussis (B. pertussis) is the traditional gold standard for laboratory diagnosis of pertussis but is insensitive, especially later in the course of illness and in vaccinated persons. Interpretation of serology is limited by the lack of an appropriate reference standard. An outbreak of pertussis in a crowded boarding-school dormitory allowed evaluation of laboratory correlates of infection. Questionnaires, serum samples and throat swabs were collected from members of the exposed group. Serum samples from unexposed controls of a similar age group were used for comparison. B. pertussis PCR was performed on throat swabs, and sera were tested for IgA antibodies against whole-cell (WC) B. pertussis antigen and IgG antibodies to pertussis toxin (PT). The Centers for Disease Control and Prevention definition for pertussis was used to define clinical cases. We evaluated the use of a previously published cut-off for PT IgG of 125 EIA units (EU)/ml. Completed questionnaires were obtained from 115 students, of whom 85 (74%) reported coughing symptoms, including 32 (28%) who met the clinical case definition for pertussis. B. pertussis was detected by PCR in 17 (15%) and WC IgA in 22 (19%) students; neither correlated with symptoms, but dormitory of residence strongly predicted PCR status. The mean PT IgG geometric mean concentration, in this situation of high pertussis exposure, correlated with severity of symptoms and was significantly higher in both symptomatic and asymptomatic children exposed during the outbreak (P&lt;0&middot;001) than in control children. A cut-off for PT IgG of 125 EU/ml was too high in an outbreak situation to be sensitive enough to identify pertussis cases. A case of pertussis in a crowded boarding-school dormitory resulted rapidly in an outbreak. Serology and PCR were useful in identifying the outbreak and commencing disease control measures. The use of serology has mostly been evaluated in community serosurveys, where it is not possible to determine if immunity reflects vaccination, asymptomatic disease or symptomatic disease. This outbreak gave us the opportunity to evaluate the value of serology and PCR in the presence of confirmed exposure to pertussis.<br /

Proteomic analysis of the postsynaptic density implicates synaptic function and energy pathways in bipolar disorder.

The postsynaptic density (PSD) contains a complex set of proteins of known relevance to neuropsychiatric disorders such as schizophrenia and bipolar disorder. We enriched for this anatomical structure in the anterior cingulate cortex of 16 bipolar disorder samples and 20 controls from the Stanley Medical Research Institute. Unbiased shotgun proteomics incorporating label-free quantitation was used to identify differentially expressed proteins. Quantitative investigation of the PSD identified 2033 proteins, among which 288 were found to be differentially expressed. Validation of expression changes of DNM1, DTNA, NDUFV2, SEPT11 and SSBP was performed by western blotting. Bioinformatics analysis of the differentially expressed proteins implicated metabolic pathways including mitochondrial function, the tricarboxylic acid cycle, oxidative phosphorylation, protein translation and calcium signaling. The data implicate PSD-associated proteins, and specifically mitochondrial function in bipolar disorder. They relate synaptic function in bipolar disorder and the energy pathways that underpin it. Overall, our findings add to a growing literature linking the PSD and mitochondrial function in psychiatric disorders generally, and suggest that mitochondrial function associated with the PSD is particularly important in bipolar disorder

Mode decomposition and Lagrangian structures of the flow dynamics in orbitally shaken bioreactors

In this study, two mode decomposition techniques were applied and compared to assess the flow dynamics in an orbital shaken bioreactor (OSB) of cylindrical geometry and flat bottom: proper orthogonal decomposition and dynamic mode decomposition. Particle Image Velocimetry (PIV) experiments were carried out for different operating conditions including fluid height, h, and shaker rotational speed, N. A detailed flow analysis is provided for conditions when the fluid and vessel motions are in-phase (Fr = 0.23) and out-of-phase (Fr = 0.47). PIV measurements in vertical and horizontal planes were combined to reconstruct low order models of the full 3D flow and to determine its Finite-Time Lyapunov Exponent (FTLE) within OSBs. The combined results from the mode decomposition and the FTLE fields provide a useful insight into the flow dynamics and Lagrangian coherent structures in OSBs and offer a valuable tool to optimise bioprocess design in terms of mixing and cell suspension. Published by AIP Publishing. https://doi.org/10.1063/1.501630

Metagenomic insights of the infant microbiome community structure and function across multiple sites in the United States

The gut microbiome plays an important role in early life, protecting newborns from enteric pathogens, promoting immune system development and providing key functions to the infant host. Currently, there are limited data to broadly assess the status of the US healthy infant gut microbiome. To address this gap, we performed a multi-state metagenomic survey and found high levels of bacteria associated with enteric inflammation (e.g. Escherichia, Klebsiella), antibiotic resistance genes, and signatures of dysbiosis, independent of location, age, and diet. Bifidobacterium were less abundant than generally expected and the species identified, including B. breve, B. longum and B. bifidum, had limited genetic capacity to metabolize human milk oligosaccharides (HMOs), while B. infantis strains with a complete capacity for HMOs utilization were found to be exceptionally rare. Considering microbiome composition and functional capacity, this survey revealed a previously unappreciated dysbiosis that is widespread in the contemporary US infant gut microbiome

Her9/Hes4 Is Required for Retinal Photoreceptor Development, Maintenance, and Survival

The intrinsic and extrinsic factors that regulate vertebrate photoreceptor specification and differentiation are complex, and our understanding of all the players is far from complete. Her9, the zebrafish ortholog of human HES4, is a basic helix-loop-helix-orange transcriptional repressor that regulates neurogenesis in several developmental contexts. We have previously shown that her9 is upregulated during chronic rod photoreceptor degeneration and regeneration in adult zebrafish, but little is known about the role of her9 during retinal development. To better understand the function of Her9 in the retina, we generated zebrafish her9 CRISPR mutants. Her9 homozygous mutants displayed striking retinal phenotypes, including decreased numbers of rods and red/green cones, whereas blue and UV cones were relatively unaffected. The reduction in rods and red/green cones correlated with defects in photoreceptor subtype lineage specification. The remaining rods and double cones displayed abnormal outer segments, and elevated levels of apoptosis. In addition to the photoreceptor defects, her9 mutants also possessed a reduced proliferative ciliary marginal zone, and decreased and disorganized Müller glia. Mutation of her9 was larval lethal, with no mutants surviving past 13 days post fertilization. Our results reveal a previously undescribed role for Her9/Hes4 in photoreceptor differentiation, maintenance, and survival