Multispectral pattern recognition reveals a diversity of clinical signs in intermediate age-related macular degeneration

PURPOSE. To develop a proof-of-concept, computational method for the quantification and classification of fundus images in intermediate age-related macular degeneration (AMD). METHODS. Multispectral, unsupervised pattern recognition was applied to 184 fundus images from 10 normal and 36 intermediate AMD eyes. The imaging results of preprocessed, grayscale images from three modalities (infrared, green, and fundus autofluorescence scanning laser ophthalmoscopy) were automatically classified into various clusters sharing a common spectral signature, using a k-means clustering algorithm. Class separability was calculated by using transformed divergence (DT). The classification results for large drusen, pigmentary abnormalities, and areas unaffected by AMD were compared against three expert observers for concordance, and to calculate sensitivity and specificity. RESULTS. Multispectral, unsupervised pattern recognition successfully identified a finite number of AMD-specific, statistically separable signatures in eyes with intermediate AMD. By using a correct classification criterion of >83% for identical clusters and a total of 1693 expert annotations, the sensitivity and specificity of multispectral pattern recognition for the detection of AMD lesions was 74% and 98%, respectively. Large drusen and pigmentary abnormalities were correctly classified in 75% and 68% of instances, respectively. CONCLUSIONS. We describe herein a novel approach for the classification of multispectral images in intermediate AMD. Automated classification of intermediate AMD, using multispectral pattern recognition, has moderate sensitivity and high specificity, when compared against clinical experts. The methods described may have a future role in AMD screening or monitoring

Dynamin-related protein 1 is required for normal mitochondrial bioenergetic and synaptic function in CA1 hippocampal neurons.

Disrupting particular mitochondrial fission and fusion proteins leads to the death of specific neuronal populations; however, the normal functions of mitochondrial fission in neurons are poorly understood, especially in vivo, which limits the understanding of mitochondrial changes in disease. Altered activity of the central mitochondrial fission protein dynamin-related protein 1 (Drp1) may contribute to the pathophysiology of several neurologic diseases. To study Drp1 in a neuronal population affected by Alzheimer's disease (AD), stroke, and seizure disorders, we postnatally deleted Drp1 from CA1 and other forebrain neurons in mice (CamKII-Cre, Drp1lox/lox (Drp1cKO)). Although most CA1 neurons survived for more than 1 year, their synaptic transmission was impaired, and Drp1cKO mice had impaired memory. In Drp1cKO cell bodies, we observed marked mitochondrial swelling but no change in the number of mitochondria in individual synaptic terminals. Using ATP FRET sensors, we found that cultured neurons lacking Drp1 (Drp1KO) could not maintain normal levels of mitochondrial-derived ATP when energy consumption was increased by neural activity. These deficits occurred specifically at the nerve terminal, but not the cell body, and were sufficient to impair synaptic vesicle cycling. Although Drp1KO increased the distance between axonal mitochondria, mitochondrial-derived ATP still decreased similarly in Drp1KO boutons with and without mitochondria. This indicates that mitochondrial-derived ATP is rapidly dispersed in Drp1KO axons, and that the deficits in axonal bioenergetics and function are not caused by regional energy gradients. Instead, loss of Drp1 compromises the intrinsic bioenergetic function of axonal mitochondria, thus revealing a mechanism by which disrupting mitochondrial dynamics can cause dysfunction of axons

Home - Based Hypertension and Physical Activity Screening by Community Health Workers in Under - Resourced South African Communities

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Dust extinction from Balmer decrements of star-forming galaxies at 0.75<z<1.5 with HST/WFC3 spectroscopy from the WISP survey

Spectroscopic observations of Halpha and Hbeta emission lines of 128 star-forming galaxies in the redshift range 0.75<z<1.5 are presented. These data were taken with slitless spectroscopy using the G102 and G141 grisms of the Wide-Field-Camera 3 (WFC3) on board the Hubble Space Telescope as part of the WFC3 Infrared Spectroscopic Parallel (WISP) survey. Interstellar dust extinction is measured from stacked spectra that cover the Balmer decrement (Halpha/Hbeta). We present dust extinction as a function of Halpha luminosity (down to 3 x 10^{41} erg/s), galaxy stellar mass (reaching 4 x 10^{8} Msun), and rest-frame Halpha equivalent width. The faintest galaxies are two times fainter in Halpha luminosity than galaxies previously studied at z~1.5. An evolution is observed where galaxies of the same Halpha luminosity have lower extinction at higher redshifts, whereas no evolution is found within our error bars with stellar mass. The lower Halpha luminosity galaxies in our sample are found to be consistent with no dust extinction. We find an anti-correlation of the [OIII]5007/Halpha flux ratio as a function of luminosity where galaxies with L_{Halpha}<5 x 10^{41} erg/s are brighter in [OIII]5007 than Halpha. This trend is evident even after extinction correction, suggesting that the increased [OIII]5007/Halpha ratio in low luminosity galaxies is likely due to lower metallicity and/or higher ionization parameters.Comment: 11 pages, 9 figures, 2 tables; version addressing the referee comment

Dynamic Interchanging Native States of Lymphotactin Examined by SNAPP-MS

The human chemokine lymphotactin (Ltn) is a remarkable protein that interconverts between two unrelated native state structures in the condensed phase. It is possible to shift the equilibrium toward either conformation with selected sequence substitutions. Previous results have shown that a disulfide-stabilized variant preferentially adopts the canonical chemokine fold (Ltn10), while a single amino acid change (W55D) favors the novel Ltn40 dimeric structure. Selective noncovalent adduct protein probing (SNAPP) is a recently developed method for examining solution phase protein structure. Herein, it is demonstrated that SNAPP can easily recognize and distinguish between the Ltn10 and Ltn40 states of lymphotactin in aqueous solution. The effects of organic denaturants, acid, and disulfide bond reduction and blocking were also examined using SNAPP for the CC3, W55D, and wild type proteins. Only disulfide reduction was shown to significantly perturb the protein, and resulted in considerably decreased adduct formation consistent with loss of tertiary/secondary structure. Cold denaturation experiments demonstrated that wild-type Ltn is the most temperature sensitive of the three proteins. Examination of the higher charge states in all experiments, which are presumed to represent transition state structures between Ltn-10 and Ltn-40, reveals increased 18C6 attachment relative to the more folded structures. This observation is consistent with increased competitive intramolecular hydrogen bonding, which may guide the transition. Experiments examining the gas phase structures revealed that all three proteins can be structurally distinguished in the gas phase. In addition, the gas phase experiments enabled identification of preferred adduct binding sites

Design of the Spitzer Space Telescope Heritage Archive

It is predicted that Spitzer Space Telescope’s cryogen will run out in April 2009, and the final reprocessing for the cryogenic mission is scheduled to end in April 2011, at which time the Spitzer archive will be transferred to the NASA/IPAC Infrared Science Archive (IRSA) for long-term curation. The Spitzer Science Center (SSC) and IRSA are collaborating to design and deploy the Spitzer Heritage Archive (SHA), which will supersede the current Spitzer archive. It will initially contain the raw and final reprocessed cryogenic science products, and will eventually incorporate the final products from the Warm mission. The SHA will be accompanied by tools deemed necessary to extract the full science content of the archive and by comprehensive documentation

Activity and Process Stability of Purified Green Pepper (Capsicum annuum) Pectin Methylesterase

Pectin methylesterase (PME) from green bell peppers (Capsicum annuum) was extracted and purified by affinity chromatography on a CNBr-Sepharose-PMEI column. A single protein peak with pectin methylesterase activity was observed. For the pepper PME, a biochemical characterization in terms of molar mass (MM), isoelectric points (pI), and kinetic parameters for activity and thermostability was performed. The optimum pH for PME activity at 22 °C was 7.5, and its optimum temperature at neutral pH was between 52.5 and 55.0 °C. The purified pepper PME required the presence of 0.13 M NaCl for optimum activity. Isothermal inactivation of purified pepper PME in 20 mM Tris buffer (pH 7.5) could be described by a fractional conversion model for lower temperatures (55?57 °C) and a biphasic model for higher temperatures (58?70 °C). The enzyme showed a stable behavior toward high-pressure/temperature treatments. Keywords: Capsicum annuum; pepper; pectin methylesterase; purification; characterization; thermal and high-pressure stabilit

Single-Cell Analysis Uncovers a Vast Diversity in Intracellular Viral Defective Interfering RNA Content Affecting the Large Cell-to-Cell Heterogeneity in Influenza A Virus Replication

Virus replication displays a large cell-to-cell heterogeneity; yet, not all sources of this variability are known. Here, we study the effect of defective interfering (DI) particle (DIP) co-infection on cell-to-cell variability in influenza A virus (IAV) replication. DIPs contain a large internal deletion in one of their eight viral RNAs (vRNA) and are, thus, defective in virus replication. Moreover, they interfere with virus replication. Using single-cell isolation and reverse transcription polymerase chain reaction, we uncovered a large between-cell heterogeneity in the DI vRNA content of infected cells, which was confirmed for DI mRNAs by single-cell RNA sequencing. A high load of intracellular DI vRNAs and DI mRNAs was found in low-productive cells, indicating their contribution to the large cell-to-cell variability in virus release. Furthermore, we show that the magnitude of host cell mRNA expression (some factors may inhibit virus replication), but not the ribosome content, may further affect the strength of single-cell virus replication. Finally, we show that the load of viral mRNAs (facilitating viral protein production) and the DI mRNA content are, independently from one another, connected with single-cell virus production. Together, these insights advance single-cell virology research toward the elucidation of the complex multi-parametric origin of the large cell-to-cell heterogeneity in virus infections