Expanding the CRISPR toolbox in Culicine mosquitoes: in vitro validation of Pol III promoters

CRISPR–Cas9-based “gene drive” technologies have been proposed as a novel and effective means of controlling human diseases vectored by mosquitoes. However, more complex designs than those demonstrated to date—and an expanded molecular toolbox with which to build them—will be required to overcome the issues of resistance formation/evolution and drive spatial/temporal limitation. Foreseeing this need, we assessed the sgRNA transcriptional activities of 33 phylogenetically diverse insect Polymerase III promoters using three disease-relevant Culicine mosquito cell lines (Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus). We show that U6 promoters work across species with a range of transcriptional activity levels and find 7SK promoters to be especially promising because of their broad phylogenetic activity. We further show that U6 promoters can be substantially truncated without affecting transcriptional levels. These results will be of great utility to researchers involved in developing the next generation of gene drives

Discrete Charge Dielectric Model of Electrostatic Energy

Studies on nanoscale materials merit careful development of an electrostatics model concerning discrete point charges within dielectrics. The discrete charge dielectric model treats three unique interaction types derived from an external source: Coulomb repulsion among point charges, direct polarization between point charges and their associated surface charge elements, and indirect polarization between point charges and surface charge elements formed by other point charges. The model yields the potential energy, U(N), stored in a general $N$ point charge system differing from conventional integral formulations, $1/2\int{\bm E}\cdot{\bm D}dV$ and $1/2\int\rho\Phi dV$, in a manner significant to the treatment of few electron systems.Comment: 1 figure, 2 parts, ep

How About Tomorrow? Optimal Procrastination and the Implications for Delay in Submitting to Conferences

In these times of academic stress in which one's time budget is a binding constraint, procrastination and delay may be an optimal response to deadlines imposed by conference organizers. We formulate a model of optimal procrastination using optimal stopping theory. Whilst the date of the conference is known and the "soft" deadline is also known by the authors of the paper, the "hard" deadline for the publication of the conference proceedings and program is only known by the organizers. Organizers possess a lower and upper limit on the numbers of participants determined by their budget and the capacity of the conference venue. The authors wold like to submit papers as late as possible subject to these constraints. The question this paper attempts to address is "What is the optimal period of procrastination for the authors?

Walrasian and Marshallian Stability: An Application to the Australian Pig industry

The Global Correspondence Principle of Samuelson states that global comparative static results hold even in the absence of an initial stable equilibrium. This principle has been applied in recent studies of international trade with variable returns to scale to resolve paradoxical results with respect to the Rybczynski and Stolper-Samuelson theorems. Takayama and Ide have shown that the principle may only apply if the initial equilibrium is Marshallian stable. This has implications for economic forecasting, in that forecasts of prices and quantities may only be valid in the presence of Marshallian stability. We estimate a Vector Error correction Model of the Australian pig industry and examine the stability of the model in both the Walrasian and Marshallian sense. We find that prior to the introduction of imports in 1990, the farm gate market was characterised by both Walrasian and Marshallian stability and after 1990 it was unstable in both senses. This suggests that market forecasts since 1990 need to be viewed with more than the usual caution

Growth Patterns in the Irish Pyridoxine Nonresponsive Homocystinuria Population and the Influence of Metabolic Control and Protein Intake

A low methionine diet is the mainstay of treatment for pyridoxine nonresponsive homocystinuria (HCU). There are various guidelines for recommended protein intakes for HCU and clinical practice varies. Poor growth has been associated with low cystine levels. This retrospective review of 48 Irish pyridoxine nonresponsive HCU patients assessed weight, height, body mass index (BMI), protein intake, and metabolic control up to 18 years at nine set time points. Patients diagnosed through newborn screening (NBS) were compared to late diagnosed (LD) patients. At 18 years the LD group (n=12, mean age at diagnosis 5.09 years) were heavier (estimated effect +4.97 Kg, P=0.0058) and taller (estimated effect +7.97 cm P=0.0204) than the NBS group (n=36). There was no difference in growth rate between the groups after 10 years of age. The HCU population were heavier and taller than the general population by one standard deviation with no difference in BMI. There was no association between intermittently low cystine levels and height. Three protein intake guidelines were compared; there was no difference in adult height between those who met the lowest of the guidelines (Genetic Metabolic Dietitians International) and those with a higher protein intake

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Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Digital spatial profiling identifies molecular changes involved in development of colitis-associated colorectal cancer

ObjectiveChronic colonic inflammation seen in inflammatory bowel disease (IBD) is a risk factor for colorectal cancer (CRC). Colitis-associated cancers (CAC) are molecularly different from sporadic CRC. This study aimed to evaluate spatially defined molecular changes associated with neoplastic progression to identify mechanisms of action and potential biomarkers for prognostication.DesignIBD patients who had undergone colectomy for treatment of their IBD or dysplasia were identified from an institutional database. Formalin-fixed paraffin embedded samples from areas of normal, inflamed, dysplastic and adenocarcinoma tissue were identified for digital spatial profiling using the Nanostring GeoMx™ Cancer Transcriptome Atlas. RNA expression and quantification of 1812 genes was measured and analysed in a spatial context to compare differences in gene expression.ResultsSixteen patients were included, nine patients had CAC, two had dysplasia only and five had colitis only. Significant, step-wise differences in gene expression were seen between tissue types, mainly involving progressive over-expression of collagen genes associated with stromal remodelling. Similarly, MYC over-expression was associated with neoplastic progression. Comparison of normal and inflamed tissue from patients who progressed to those who did not also showed significant differences in immune-related genes, including under-expression of thte chemokines CCL18, CCL25 and IL-R7, as well as CD3, CD6 and lysozyme. The known oncogene CD24 was significantly overexpressed.ConclusionBoth tissue types and patient groups are molecularly distinguishable on the basis of their gene expression patterns. Further prospective work is necessary to confirm these differences and establish their clinical significance and potential utility as biomarkers