Optic Disc Swelling and Vision Loss in a Patient with Cystic Fibrosis and Diabetes

Advances in cystic fibrosis management have significantly improved life expectancy in these patients. However, we are now faced with a growing number of long-term extrapulmonary consequences of this disease, including ophthalmic complications of diabetes in cystic fibrosis patients. We present a unique report that documents a case of diabetic papillopathy progressing to nonarteritic anterior ischemic optic neuropathy resulting in vision loss in a patient with CF and diabetes. It highlights the potentially devastating consequences of longstanding diabetes in CF patients

Metallopanstimulin as a marker for head and neck cancer

BACKGROUND: Metallopanstimulin (MPS-1) is a ribosomal protein that is found in elevated amounts in the sera of patients with head and neck squamous cell carcinoma (HNSCC). We used a test, denoted MPS-H, which detects MPS-1 and MPS-1-like proteins, to determine the relationship between MPS-H serum levels and clinical status of patients with, or at risk for, HNSCC. PATIENTS AND METHODS: A total of 125 patients were prospectively enrolled from a university head and neck oncology clinic. Participants included only newly diagnosed HNSCC patients. Two control groups, including 25 non-smokers and 64 smokers, were studied for comparison. A total of 821 serum samples collected over a twenty-four month period were analyzed by the MPS-H radioimmunoassay. RESULTS: HNSCC, non-smokers, and smokers had average MPS-H values of 41.5 ng/mL, 10.2 ng/mL, and 12.8 ng/mL, respectively (p = 0.0001). CONCLUSION: We conclude that MPS-1 and MPS-1-like proteins are elevated in patients with HNSCC, and that MPS-H appears to be a promising marker of presence of disease and response to treatment in HNSCC patients

Cellular localization, accumulation and trafficking of double-walled carbon nanotubes in human prostate cancer cells

Carbon nanotubes (CNTs) are at present being considered as potential nanovectors with the ability to deliver therapeutic cargoes into living cells. Previous studies established the ability of CNTs to enter cells and their therapeutic utility, but an appreciation of global intracellular trafficking associated with their cellular distribution has yet to be described. Despite the many aspects of the uptake mechanism of CNTs being studied, only a few studies have investigated internalization and fate of CNTs inside cells in detail. In the present study, intracellular localization and trafficking of RNA-wrapped, oxidized double-walled CNTs (oxDWNT–RNA) is presented. Fixed cells, previously exposed to oxDWNT–RNA, were subjected to immunocytochemical analysis using antibodies specific to proteins implicated in endocytosis; moreover cell compartment markers and pharmacological inhibitory conditions were also employed in this study. Our results revealed that an endocytic pathway is involved in the internalization of oxDWNT–RNA. The nanotubes were found in clathrin-coated vesicles, after which they appear to be sorted in early endosomes, followed by vesicular maturation, become located in lysosomes. Furthermore, we observed co-localization of oxDWNT–RNA with the small GTP-binding protein (Rab 11), involved in their recycling back to the plasma membrane via endosomes from the trans-golgi network

Facilitation and herbivory in Southern California coastal sage scrub

Recent and significant environmental changes have greatly affected native plant recruitment and re-establishment in patchy Mediterranean plant communities. Prolonged drought, urban development, and invasion by non-native annual plants have created a mix of dead shrubs and bare areas in Southern California coastal sage scrub (CSS) habitat. Established shrubs in CSS may be important in facilitation of the germination, growth, and establishment of nearby native plant seedlings, especially during extended periods of drought. Facilitation is a positive plant-plant interaction, where neighboring species benefit from shared resources and protection from abiotic stresses. It is used commonly in restoration practice in arid or resource-limited environments, when seedlings are planted under or near mature trees and shrubs. Though living plants strongly influence plant community structure and interactions, there is little information about the influence of dead shrubs in semi-arid Mediterranean environments. Biotic pressures such as herbivory on native recruitment in these plant communities are also not well understood. I conducted an experiment in a degraded CSS plant community to investigate whether seedling germination, growth, and survival depends on abiotic factors (microclimate conditions under shrubs), or on biotic factors (herbivory). Two native woody shrubs (Artemisia californica and Salvia mellifera) were planted and four native annual species (Amsinckia intermedia, Deinandra fasciculata, Phacelia distans, and Pseudognaphalium californicum) were sown in five blocks with three Shrub Type treatments (live shrub, dead shrub, and exposed areas), with a nested Cage treatment (no cage and cage) in each Shrub Type treatment. Environmental sensors and trail cameras were installed to measure abiotic factors and estimate herbivore visitation. The number of seedlings, seedling growth rate, biomass, chlorophyll fluorescence, leaf water potential, and abiotic data were measured and analyzed to determine abiotic and biotic effects on growth and survivorship in all treatments. I found that biotic pressures (herbivory) influenced native annual seedling recruitment; the number of native annual seedlings was greatest in caged areas. Caged plants across all Shrub Types were significantly larger than uncaged plants. Furthermore, caged A. californica and S. mellifera seedling growth responses differed slightly under live and dead shrubs due to light limitation. While caged A. californica grew tall under dead shrubs, it did not grow large, and caged S. mellifera did not grow tall or large under shrubs at all. Overall, there was little evidence of facilitation for all plant species tested, perhaps because CSS is a mild, semi-arid environment compared to other habitats where facilitative interactions are stronger, such as arid deserts. In this study, herbivory was a great barrier to seedling establishment, growth, and survival for unprotected plants in degraded CSS. Moving forward, results from this experiment suggest that protecting A. californica seedlings with cages or planting species with anti-herbivory traits around target plants may be more strategic approaches in restoring degraded CSS after extended drought

Influence of packing density and surface roughness of vertically-aligned carbon nanotubes on adhesive properties of gecko-inspired mimetics.

We have systematically studied the macroscopic adhesive properties of vertically aligned nanotube arrays with various packing density and roughness. Using a tensile setup in shear and normal adhesion, we find that there exists a maximum packing density for nanotube arrays to have adhesive properties. Too highly packed tubes do not offer intertube space for tube bending and side-wall contact to surfaces, thus exhibiting no adhesive properties. Likewise, we also show that the surface roughness of the arrays strongly influences the adhesion properties and the reusability of the tubes. Increasing the surface roughness of the array strengthens the adhesion in the normal direction, but weakens it in the shear direction. Altogether, these results allow progress toward mimicking the gecko's vertical mobility.The authors acknowledge funding from the EC project Technotubes.This is the accepted manuscript. The final version is available at http://pubs.acs.org/doi/abs/10.1021/am507822b

Wind farm structural response and wake dynamics for an evolving stable boundary layer: computational and experimental comparisons

The wind turbine design process requires performing thousands of simulations for a wide range of inflow and control conditions, which necessitates computationally efficient yet time-accurate models, especially when considering wind farm settings. To this end, FAST.Farm is a dynamic-wake-meandering-based mid-fidelity engineering tool developed by the National Renewable Energy Laboratory targeted at accurately and efficiently predicting wind turbine power production and structural loading in wind farm settings, including wake interactions between turbines. This work is an extension of a study that addressed constructing a diurnal cycle evolution based on experimental data (Quon, 2024). Here, this inflow is used to validate the turbine structural and wake-meandering response between experimental data, FAST.Farm simulation results, and high-fidelity large-eddy simulation results from the coupled Simulator fOr Wind Farm Applications (SOWFA)–OpenFAST tool. The validation occurs within the nocturnal stable boundary layer when corresponding meteorological and turbine data are available. To this end, we compared the load results from FAST.Farm and SOWFA–OpenFAST to multi-turbine measurements from a subset of a full-scale wind farm. Computational predictions of blade-root and tower-base bending loads are compared to 10 min statistics of strain gauge measurements during 3.5 h of the evolving stable boundary layer, generally with good agreement. This time period coincided with an active wake-steering campaign of an upstream turbine, resulting in time-varying yaw positions of all turbines. Wake meandering was also compared between the computational solutions, generally with excellent agreement. Simulations were based on a high-fidelity precursor constructed from inflow measurements and using state-of-the-art mesoscale-to-microscale coupling.</p

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.Postprint (published version

Regulatory (pan-)genome of an obligate intracellular pathogen in the PVC superphylum.

Like other obligate intracellular bacteria, the Chlamydiae feature a compact regulatory genome that remains uncharted owing to poor genetic tractability. Exploiting the reduced number of transcription factors (TFs) encoded in the chlamydial (pan-)genome as a model for TF control supporting the intracellular lifestyle, we determined the conserved landscape of TF specificities by ChIP-Seq (chromatin immunoprecipitation-sequencing) in the chlamydial pathogen Waddlia chondrophila. Among 10 conserved TFs, Euo emerged as a master TF targeting &gt;100 promoters through conserved residues in a DNA excisionase-like winged helix-turn-helix-like (wHTH) fold. Minimal target (Euo) boxes were found in conserved developmentally-regulated genes governing vertical genome transmission (cytokinesis and DNA replication) and genome plasticity (transposases). Our ChIP-Seq analysis with intracellular bacteria not only reveals that global TF regulation is maintained in the reduced regulatory genomes of Chlamydiae, but also predicts that master TFs interpret genomic information in the obligate intracellular α-proteobacteria, including the rickettsiae, from which modern day mitochondria evolved

Sex-specific single cell-level transcriptomic signatures of Rett syndrome disease progression

Dominant X-linked diseases are uncommon due to female X chromosome inactivation (XCI). While random XCI usually protects females against X-linked mutations, Rett syndrome (RTT) is a female neurodevelopmental disorder caused by heterozygous MECP2 mutation. After 6-18 months of typical neurodevelopment, RTT girls undergo a poorly understood regression. We performed longitudinal snRNA-seq on cerebral cortex in a construct-relevant Mecp2e1 mutant mouse model of RTT, revealing transcriptional effects of cell type, mosaicism, and sex on progressive disease phenotypes. Across cell types, we observed sex differences in the number of differentially expressed genes (DEGs) with 6x more DEGs in mutant females than males. Unlike males, female DEGs emerged prior to symptoms, were enriched for homeostatic gene pathways in distinct cell types over time and correlated with disease phenotypes and human RTT cortical cell transcriptomes. Non-cell-autonomous effects were prominent and dynamic across disease progression of Mecp2e1 mutant females, indicating that wild-type-expressing cells normalize transcriptional homeostasis. These results advance our understanding of RTT progression and treatment