Controlled interfacial assembly of 2D curved colloidal crystals and jammed shells

Assembly of colloidal particles on fluid interfaces is a promising technique for synthesizing two-dimensional micro-crystalline materials useful in fields as diverse as biomedicine1, materials science2, mineral flotation3 and food processing4. Current approaches rely on bulk emulsification methods, require further chemical and thermal treatments, and are restrictive with respect to the materials employed5-9. The development of methods that exploit the great potential of interfacial assembly for producing tailored materials have been hampered by the lack of understanding of the assembly process. Here we report a microfluidic method that allows direct visualization and understanding of the dynamics of colloidal crystal growth on curved interfaces. The crystals are periodically ejected to form stable jammed shells, which we refer to as colloidal armour. We propose that the energetic barriers to interfacial crystal growth and organization can be overcome by targeted delivery of colloidal particles through hydrodynamic flows. Our method allows an unprecedented degree of control over armour composition, size and stability.Comment: 18 pages, 5 figure

Evaluation of Magnetic Micro- and Nanoparticle Toxicity to Ocular Tissues

Purpose: Magnetic nanoparticles (MNPs) may be used for focal delivery of plasmids, drugs, cells, and other applications. Here we ask whether such particles are toxic to ocular structures. Methods: To evaluate the ocular toxicity of MNPs, we asked if either 50 nm or 4 mm magnetic particles affect intraocular pressure, corneal endothelial cell count, retinal morphology including both cell counts and glial activation, or photoreceptor function at different time points after injection. Sprague-Dawley rats (n = 44) were injected in the left eye with either 50 nm (3 ml, 1.65 mg) or 4 mm(3ml, 1.69 mg) magnetic particles, and an equal volume of PBS into the right eye. Electroretinograms (ERG) were used to determine if MNPs induce functional changes to the photoreceptor layers. Enucleated eyes were sectioned for histology and immunofluorescence. Results: Compared to control-injected eyes, MNPs did not alter IOP measurements. ERG amplitudes for a-waves were in the 100–250 mV range and b-waves were in the 500–600 mV range, with no significant differences between injected and noninjected eyes. Histological sectioning and immunofluorescence staining showed little difference in MNP-injected animals compared to control eyes. In contrast, at 1 week, corneal endothelial cell numbers were significantly lower in the 4 mm magnetic particle-injected eyes compared to either 50 nm MNP- or PBS-injected eyes. Furthermore, iron deposition was detected after 4 mm magnetic particle but not 50 nm MNP injection

Comparative proteomics using 2-D gel electrophoresis and mass spectrometry as tools to dissect stimulons and regulons in bacteria with sequenced or partially sequenced genomes

We propose two-dimensional gel electrophoresis (2-DE) and mass spectrometry to define the protein components of regulons and stimulons in bacteria, including those organisms where genome sequencing is still in progress. The basic 2-DE protocol allows high resolution and reproducibility and enables the direct comparison of hundreds or even thousands of proteins simultaneously. To identify proteins that comprise stimulons and regulons, peptide mass fingerprint (PMF) with matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF-MS) analysis is the first option and, if results from this tool are insufficient, complementary data obtained with electrospray ionization tandem-MS (ESI-MS/MS) may permit successful protein identification. ESI-MS/MS and MALDI-TOF-MS provide complementary data sets, and so a more comprehensive coverage of a proteome can be obtained using both techniques with the same sample, especially when few sequenced proteins of a particular organism exist or genome sequencing is still in progress

Genome-Wide Identification of Alternatively Spliced mRNA Targets of Specific RNA-Binding Proteins

BACKGROUND: Alternative splicing plays an important role in generating molecular and functional diversity in multi-cellular organisms. RNA binding proteins play crucial roles in modulating splice site choice. The majority of known binding sites for regulatory proteins are short, degenerate consensus sequences that occur frequently throughout the genome. This poses an important challenge to distinguish between functionally relevant sequences and a vast array of those occurring by chance. METHODOLOGY/PRINCIPAL FINDINGS: Here we have used a computational approach that combines a series of biological constraints to identify uridine-rich sequence motifs that are present within relevant biological contexts and thus are potential targets of the Drosophila master sex-switch protein Sex-lethal (SXL). This strategy led to the identification of one novel target. Moreover, our systematic analysis provides a starting point for the molecular and functional characterization of an additional target, which is dependent on SXL activity, either directly or indirectly, for regulation in a germline-specific manner. CONCLUSIONS/SIGNIFICANCE: This approach has successfully identified previously known, new, and potential SXL targets. Our analysis suggests that only a subset of potential SXL sites are regulated by SXL. Finally, this approach should be directly relevant to the large majority of splicing regulatory proteins for which bonafide targets are unknown

Comparative Genomic Hybridization (CGH) Reveals a Neo-X Chromosome and Biased Gene Movement in Stalk-Eyed Flies (Genus Teleopsis)

Chromosomal location has a significant effect on the evolutionary dynamics of genes involved in sexual dimorphism, impacting both the pattern of sex-specific gene expression and the rate of duplication and protein evolution for these genes. For nearly all non-model organisms, however, knowledge of chromosomal gene content is minimal and difficult to obtain on a genomic scale. In this study, we utilized Comparative Genomic Hybridization (CGH), using probes designed from EST sequence, to identify genes located on the X chromosome of four species in the stalk-eyed fly genus Teleopsis. Analysis of log2 ratio values of female-to-male hybridization intensities from the CGH microarrays for over 3,400 genes reveals a strongly bimodal distribution that clearly differentiates autosomal from X-linked genes for all four species. Genotyping of 33 and linkage mapping of 28 of these genes in Teleopsis dalmanni indicate the CGH results correctly identified chromosomal location in all cases. Syntenic comparison with Drosophila indicates that 90% of the X-linked genes in Teleopsis are homologous to genes located on chromosome 2L in Drosophila melanogaster, suggesting the formation of a nearly complete neo-X chromosome from Muller element B in the dipteran lineage leading to Teleopsis. Analysis of gene movement both relative to Drosophila and within Teleopsis indicates that gene movement is significantly associated with 1) rates of protein evolution, 2) the pattern of gene duplication, and 3) the evolution of eyespan sexual dimorphism. Overall, this study reveals that diopsids are a critical group for understanding the evolution of sex chromosomes within Diptera. In addition, we demonstrate that CGH is a useful technique for identifying chromosomal sex-linkage and should be applicable to other organisms with EST or partial genomic information

Translational models for vascular cognitive impairment: a review including larger species.

BACKGROUND: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited. METHODS: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, hyperhomocysteinemia, high-salt/high-fat diet) or reproduce genetic causes of VCI (CADASIL-causing Notch3 mutations). CONCLUSIONS: We concluded that (1) translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; (2) rodent models of VCI are limited by paucity of white matter; and (3) further translational models, and improved cognitive testing instruments, are required

Meat and Nicotinamide:A Causal Role in Human Evolution, History, and Demographics

Hunting for meat was a critical step in all animal and human evolution. A key brain-trophic element in meat is vitamin B 3 /nicotinamide. The supply of meat and nicotinamide steadily increased from the Cambrian origin of animal predators ratcheting ever larger brains. This culminated in the 3-million-year evolution of Homo sapiens and our overall demographic success. We view human evolution, recent history, and agricultural and demographic transitions in the light of meat and nicotinamide intake. A biochemical and immunological switch is highlighted that affects fertility in the ‘de novo’ tryptophan-to-kynurenine-nicotinamide ‘immune tolerance’ pathway. Longevity relates to nicotinamide adenine dinucleotide consumer pathways. High meat intake correlates with moderate fertility, high intelligence, good health, and longevity with consequent population stability, whereas low meat/high cereal intake (short of starvation) correlates with high fertility, disease, and population booms and busts. Too high a meat intake and fertility falls below replacement levels. Reducing variances in meat consumption might help stabilise population growth and improve human capital

Prognostic Factors for Survival in Hepatocellular Carcinoma

Associations between patient characteristics and survival were investigated in 432 patients with hepatocellular carcinoma. Those patients were prospectively studied by the Eastern Cooperative Oncology Group, and each had his or her diagnosis reconfirmed by a pathology review panel. There were 301 North American and 131 South African patients. Sixty-nine % of the North American patients and 82% of the South African patients were male. There were 187 Black patients, 62 of whom were from North America. The study population is unique among hepatocellular carcinoma patients in that eligibility, evaluability, and endpoint definitions were standardized, and patients from both North America and South Africa received similar treatments at a similar time. Factors with the most significant adverse effect on survival are impaired performance status, male sex, older age, and disease symptoms (jaundice and reduced appetite). There is no apparent difference in survival between White and Black patients within North America, but North American patients survived longer than South African patients. Among the different therapies, p.o. 5-fluorouracil was associated with the poorest median survival time (6 wk), and i.v. 5-fluorouracil plus semustine with the best median survival time (24 wk). © 1988, American Association for Cancer Research. All rights reserved

PALA versus streptozotocin, doxorubicin, and MeCCNU in the treatment of patients with advanced pancreatic carcinoma

Seventy-three eligible, chemotherapy-naive, ambulatory patients with advanced pancreatic carcinoma were allocated to one of two treatment regimens: 35 received PALA (1250 mg/m2 daily x 5 every 4 weeks) and 38 were given SAM (streptozotocin 400 mg/m2 IV daily x 5, doxorubicin 45 mg/m2 IV on day 1 and 22, and methyl CCNU 60 mg/m2 orally on days 1 and 22 every 6 weeks). Doses were modified for myelo-, gi-, or cardiotoxicity. Adequate organ, bone marrow and cardiac function; a measurable lesion; adequate caloric intake; and a life expectancy of 2 months were required for treatment on this trial. One patient on each regimen had a partial response for response rates of 3% (95% confidence intervals, 0.08 to 17%). Median survival on the PALA arm was 5 months and median time to treatment failure was 2.6 months. SAM patients experienced median overall and progression free survivals of 3.4 and 1.9 months, respectively. The severe toxicity observed was almost exclusively myelosuppression on both regimens. One patient receiving SAM had lethal leukopenic sepsis during the first cycle as the only treatment-related death. Neither PALA nor SAM offer any therapeutic utility to patients with advanced pancreatic cancer

Oxidative passivation of metal halide perovskites

Metal halide perovskites have demonstrated extraordinary potential as materials for next-generation optoelectronics including photovoltaics and light-emitting diodes. Nevertheless, our understanding of this material is still far from complete. One remaining puzzle is the phenomenon of perovskite “photo-brightening”: the increase in photoluminescence during exposure to light in an ambient atmosphere. Here, we propose a comprehensive mechanism for the reactivity of the archetypal perovskite, MAPbI3, in ambient conditions. We establish the formation of lead-oxygen bonds by hydrogen peroxide as the key factor leading to perovskite photo-brightening. We demonstrate that hydrogen peroxide can be applied directly as an effective “post-treatment” to emulate the process and substantially improve photoluminescence quantum efficiencies. Finally, we show that the treatment can be incorporated into photovoltaic devices to give a 50 mV increase in open-circuit voltage, delivering high 19.2% steady-state power conversion efficiencies for inverted perovskite solar cells of the mixed halide, mixed cation perovskite FA0.83Cs0.17Pb(I0.9Br0.1)3