Cell wall chitosan is necessary for virulence in the opportunistic pathogen Cryptococcus neoformans

Cryptococcus neoformans is an opportunistic fungal pathogen that causes meningoencephalitis. Its cell wall is composed of glucans, proteins, chitin, and chitosan. Multiple genetic approaches have defined a chitosan-deficient syndrome that includes slow growth and decreased cell integrity. Here we demonstrate chitosan is necessary for virulence and persistence in the mammalian host

Inside Out: Detecting Learners' Confusion to Improve Interactive Digital Learning Environments

Confusion is an emotion that is likely to occur while learning complex information. This emotion can be beneficial to learners in that it can foster engagement, leading to deeper understanding. However, if learners fail to resolve confusion, its effect can be detrimental to learning. Such detrimental learning experiences are particularly concerning within digital learning environments (DLEs), where a teacher is not physically present to monitor learner engagement and adapt the learning experience accordingly. However, with better information about a learner's emotion and behavior, it is possible to improve the design of interactive DLEs (IDLEs) not only in promoting productive confusion but also in preventing overwhelming confusion. This article reviews different methodological approaches for detecting confusion, such as self-report and behavioral and physiological measures, and discusses their implications within the theoretical framework of a zone of optimal confusion. The specificities of several methodologies and their potential application in IDLEs are discussed

Short Time Behavior in De Gennes' Reptation Model

To establish a standard for the distinction of reptation from other modes of polymer diffusion, we analytically and numerically study the displacement of the central bead of a chain diffusing through an ordered obstacle array for times $t < O(N^2)$. Our theory and simulations agree quantitatively and show that the second moment approaches the $t^{1/4}$ often viewed as signature of reptation only after a very long transient and only for long chains (N > 100). Our analytically solvable model furthermore predicts a very short transient for the fourth moment. This is verified by computer experiment.Comment: 4 pages, revtex, 4 ps file

Loss of solutions in shear banding fluids in shear banding fluids driven by second normal stress differences

Edge fracture occurs frequently in non-Newtonian fluids. A similar instability has often been reported at the free surface of fluids undergoing shear banding, and leads to expulsion of the sample. In this paper the distortion of the free surface of such a shear banding fluid is calculated by balancing the surface tension against the second normal stresses induced in the two shear bands, and simultaneously requiring a continuous and smooth meniscus. We show that wormlike micelles typically retain meniscus integrity when shear banding, but in some cases can lose integrity for a range of average applied shear rates during which one expects shear banding. This meniscus fracture would lead to ejection of the sample as the shear banding region is swept through. We further show that entangled polymer solutions are expected to display a propensity for fracture, because of their much larger second normal stresses. These calculations are consistent with available data in the literature. We also estimate the meniscus distortion of a three band configuration, as has been observed in some wormlike micellar solutions in a cone and plate geometry.Comment: 23 pages, to be published in Journal of Rheolog

The Sagnac Phase Shift suggested by the Aharonov-Bohm effect for relativistic matter beams

The phase shift due to the Sagnac Effect, for relativistic matter beams counter-propagating in a rotating interferometer, is deduced on the bases of a a formal analogy with the the Aharonov-Bohm effect. A procedure outlined by Sakurai, in which non relativistic quantum mechanics and newtonian physics appear together with some intrinsically relativistic elements, is generalized to a fully relativistic context, using the Cattaneo's splitting technique. This approach leads to an exact derivation, in a self-consistently relativistic way, of the Sagnac effect. Sakurai's result is recovered in the first order approximation.Comment: 18 pages, LaTeX, 2 EPS figures. To appear in General Relativity and Gravitatio

The Aminoalkylindole BML-190 Negatively Regulates Chitosan Synthesis via the Cyclic AMP/Protein Kinase A1 Pathway in Cryptococcus neoformans

Cryptococcus neoformans can cause fatal meningoencephalitis in patients with AIDS or other immunocompromising conditions. Current antifungals are suboptimal to treat this disease; therefore, novel targets and new therapies are needed. Previously, we have shown that chitosan is a critical component of the cryptococcal cell wall and is required for survival in the mammalian host and that chitosan deficiency results in rapid clearance from the mammalian host. We had also identified several specific proteins that were required for chitosan biosynthesis, and we hypothesize that screening for compounds that inhibit chitosan biosynthesis would identify additional genes/proteins that influence chitosan biosynthesis. To identify these compounds, we developed a robust and novel cell-based flow cytometry screening method to identify small-molecule inhibitors of chitosan production. We screened the ICCB Known Bioactives library and identified 8 compounds that reduced chitosan in C. neoformans We used flow cytometry-based counterscreens and confirmatory screens, followed by a biochemical secondary screen to refine our primary screening hits to 2 confirmed hits. One of the confirmed hits that reduced chitosan content was the aminoalkylindole BML-190, a known inverse agonist of mammalian cannabinoid receptors. We demonstrated that BML-190 likely targets the C. neoformans G-protein-coupled receptor Gpr4 and, via the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway, contributes to an intracellular accumulation of cAMP that results in decreased chitosan. Our discovery suggests that this approach could be used to identify additional compounds and pathways that reduce chitosan biosynthesis and could lead to potential novel therapeutics against C. neoformans IMPORTANCE Cryptococcus neoformans is a fungal pathogen that kills approximately 200,000 people every year. The cell wall is an essential organelle that protects fungi from the environment. Chitosan, the deacetylated form of chitin, has been shown to be an essential component of the cryptococcal cell wall during infection of a mammalian host. In this study, we screened a set of 480 compounds, which are known to have defined biological activities, for activity that reduced chitosan production in C. neoformans Two of these compounds were confirmed using an alternative method of measuring chitosan, and one of these was demonstrated to impact the cAMP signal transduction pathway. This work demonstrates that the cAMP pathway regulates chitosan biosynthesis in C. neoformans and validates that this screening approach could be used to find potential antifungal agents

Whitehall in the Caribbean? The legacy of colonial administration for post-colonial democratic development

Colonial-era administrative institutions and doctrines are fundamental to any analysis of Westminster’s legacy in the Caribbean. Applying the lens of ‘Public Service Bargains’ (PSBs) – the formal and informal understandings of reward, competence and loyalty of public servants –we first examine constitutional and administrative doctrines regarding the public service of Crown Colonies, before analysing how these worked themselves out in Jamaica. Our analysis reveals a number of perceived deficiencies in the PSB in the pre-independence period that cast a shadow on future relations in the post-independence period