Dynamics of viscoelastic membranes

We determine both the in-plane and out-of-plane dynamics of viscoelastic membranes separating two viscous fluids in order to understand microrheological studies of such membranes. We demonstrate the general viscoelastic signatures in the dynamics of shear, bending, and compression modes. We also find a screening of the otherwise two-dimensional character of the response to point forces due to the presence of solvent. Finally, we show that there is a linear, hydrodynamic coupling between the in-plane compression modes of the membrane and the out-of-plane bending modes in the case where the membrane separates two different fluids or environments

Two-point microrheology and the electrostatic analogy

The recent experiments of Crocker et al. suggest that microrheological measurements obtained from the correlated fluctuations of widely-separatedprobe particles determine the rheological properties of soft, complex materials more accurately than do the more traditional particle autocorrelations. This presents an interesting problem in viscoelastic dynamics. We develop an important, simplifing analogy between the present viscoelastic problem and classical electrostatics. Using this analogy and direct calculation we analyze both the one and two particle correlations in a viscoelastic medium in order to explain this observation

One- and two-particle microrheology

We study the dynamics of rigid spheres embedded in viscoelastic media and address two questions of importance to microrheology. First we calculate the complete response to an external force of a single bead in a homogeneous elastic network viscously coupled to an incompressible fluid. From this response function we find the frequency range where the standard assumptions of microrheology are valid. Second we study fluctuations when embedded spheres perturb the media around them and show that mutual fluctuations of two separated spheres provide a more accurate determination of the complex shear modulus than do the fluctuations of a single sphere.Comment: 4 pages, 1 figur

The response function of a sphere in a viscoelastic two-fluid medium

In order to address basic questions of importance to microrheology, we study the dynamics of a rigid sphere embedded in a model viscoelastic medium consisting of an elastic network permeated by a viscous fluid. We calculate the complete response of a single bead in this medium to an external force and compare the result to the commonly-accepted, generalized Stokes-Einstein relation (GSER). We find that our response function is well approximated by the GSER only within a particular frequency range determined by the material parameters of both the bead and the network. We then discuss the relevance of this result to recent experiments. Finally we discuss the approximations made in our solution of the response function by comparing our results to the exact solution for the response function of a bead in a viscous (Newtonian) fluid.Comment: 12 pages, 2 figure

Trans-national conservation and infrastructure development in the Heart of Borneo

The Heart of Borneo initiative has promoted the integration of protected areas and sustainably-managed forests across Malaysia, Indonesia, and Brunei. Recently, however, member states of the Heart of Borneo have begun pursuing ambitious unilateral infrastructure-development schemes to accelerate economic growth, jeopardizing the underlying goal of trans-boundary integrated conservation. Focusing on Sabah, Malaysia, we highlight conflicts between its Pan-Borneo Highway scheme and the regional integration of protected areas, unprotected intact forests, and conservation-priority forests. Road developments in southern Sabah in particular would drastically reduce protected-area integration across the northern Heart of Borneo region. Such developments would separate two major clusters of protected areas that account for one-quarter of all protected areas within the Heart of Borneo complex. Sabah has proposed forest corridors and highway underpasses as means of retaining ecological connectivity in this context. Connectivity modelling identified numerous overlooked areas for connectivity rehabilitation among intact forest patches following planned road development. While such ‘linear-conservation planning’ might theoretically retain up to 85% of intact-forest connectivity and integrate half of the conservation-priority forests across Sabah, in reality it is very unlikely to achieve meaningful ecological integration. Moreover, such measure would be exceedingly costly if properly implemented–apparently beyond the operating budget of relevant Malaysian authorities. Unless critical road segments are cancelled, planned infrastructure will fragment important conservation landscapes with little recourse for mitigation. This likelihood reinforces earlier calls for the legal recognition of the Heart of Borneo region for conservation planning as well as for enhanced tri-lateral coordination of both conservation and development

A Liposome-Micelle-Hybrid (LMH) Oral Delivery System for Poorly Water-Soluble Drugs: Enhancing Solubilisation and Intestinal Transport

A novel liposome-micelle-hybrid (LMH) carrier system was developed as a superior oral drug delivery platform compared to conventional liposome or micelle formulations. The optimal LMH system was engineered by encapsulating TPGS micelles in the aqueous core of liposomes and its efficacy for oral delivery was demonstrated using lovastatin (LOV) as a model poorly soluble drug with P-gp (permeability glycoprotein) limited intestinal absorption. LOV-LMH was characterised as unilamellar, spherical vesicles encapsulating micellar structures within the interior aqueous core and showing an average diameter below 200 nm. LMH demonstrated enhanced drug loading, water apparent solubility and extended/controlled release of LOV compared to conventional liposomes and micelles. LMH exhibited enhanced LOV absorption and transportation in a Caco-2 cell monolayer model of the intestine by inhibiting the P-gp transporter system compared to free LOV. The LMH system is a promising novel oral delivery approach for enhancing bioavailability of poorly water-soluble drugs, especially those presenting P-gp effluxes limited absorption

Patterns of predation and meat-eating by chacma baboons in an Afromontane environment

Meat-eating among non-human primates has been well documented but its prevalence among Afromontane baboons is understudied. In this study we report the predatory and meat-eating behaviours of a habituated group of gray-footed chacma baboons (Papio ursinus griseipes) living in an Afromontane environment in South Africa. We calculated a vertebrate-eating rate of 1 every 78.5 hours, increasing to 58.1 hours when unsuccessful predation attempts were included. A key food source was young antelopes, particularly bushbuck (Tragelaphus scriptus), which were consumed once every 115 observation hours. Similar to other baboon research sites, predations seemed mostly opportunistic, adult males regularly scrounged and monopolised prey, there was no evidence they used an active kill bite, and active sharing was absent. This is the first baboon study to report predation of rock python (Python sebae) eggs and likely scavenging of a leopard (Panthera pardus) kill (bushbuck) cached in a tree. We also describe several scramble kleptoparasitism events, tolerating active defence from antelope parents, and the baboons inhibiting public information about predations. In the latter case, baboons with meat often hid beyond the periphery of the group, reducing the likelihood of scrounging by competitors. This often led to prey carcasses being discarded without being fully exploited and potentially providing resources to scavengers. We also highlight the absence of encounters with numerous species, suggesting the baboons are a key component of several species’ landscapes of fear. Given these findings it seems likely that their ecological role in the Soutpansberg has been undervalued, and such conclusions may also hold for other baboon populations

A pleurocidin analogue with greater conformational flexibility, enhanced antimicrobial potency and in vivo therapeutic efficacy.

Antimicrobial peptides (AMPs) are a potential alternative to classical antibiotics that are yet to achieve a therapeutic breakthrough for treatment of systemic infections. The antibacterial potency of pleurocidin, an AMP from Winter Flounder, is linked to its ability to cross bacterial plasma membranes and seek intracellular targets while also causing membrane damage. Here we describe modification strategies that generate pleurocidin analogues with substantially improved, broad spectrum, antibacterial properties, which are effective in murine models of bacterial lung infection. Increasing peptide-lipid intermolecular hydrogen bonding capabilities enhances conformational flexibility, associated with membrane translocation, but also membrane damage and potency, most notably against Gram-positive bacteria. This negates their ability to metabolically adapt to the AMP threat. An analogue comprising D-amino acids was well tolerated at an intravenous dose of 15 mg/kg and similarly effective as vancomycin in reducing EMRSA-15 lung CFU. This highlights the therapeutic potential of systemically delivered, bactericidal AMPs

The physics of spreading processes in multilayer networks

The study of networks plays a crucial role in investigating the structure, dynamics, and function of a wide variety of complex systems in myriad disciplines. Despite the success of traditional network analysis, standard networks provide a limited representation of complex systems, which often include different types of relationships (i.e., "multiplexity") among their constituent components and/or multiple interacting subsystems. Such structural complexity has a significant effect on both dynamics and function. Throwing away or aggregating available structural information can generate misleading results and be a major obstacle towards attempts to understand complex systems. The recent "multilayer" approach for modeling networked systems explicitly allows the incorporation of multiplexity and other features of realistic systems. On one hand, it allows one to couple different structural relationships by encoding them in a convenient mathematical object. On the other hand, it also allows one to couple different dynamical processes on top of such interconnected structures. The resulting framework plays a crucial role in helping achieve a thorough, accurate understanding of complex systems. The study of multilayer networks has also revealed new physical phenomena that remain hidden when using ordinary graphs, the traditional network representation. Here we survey progress towards attaining a deeper understanding of spreading processes on multilayer networks, and we highlight some of the physical phenomena related to spreading processes that emerge from multilayer structure.Comment: 25 pages, 4 figure

Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity: Mendelian randomisation using polygenic risk scores.

BACKGROUND: Greater maternal adiposity before or during pregnancy is associated with greater offspring adiposity throughout childhood, but the extent to which this is due to causal intrauterine or periconceptional mechanisms remains unclear. Here, we use Mendelian randomisation (MR) with polygenic risk scores (PRS) to investigate whether associations between maternal pre-/early pregnancy body mass index (BMI) and offspring adiposity from birth to adolescence are causal. METHODS: We undertook confounder adjusted multivariable (MV) regression and MR using mother-offspring pairs from two UK cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) and Born in Bradford (BiB). In ALSPAC and BiB, the outcomes were birthweight (BW; N = 9339) and BMI at age 1 and 4 years (N = 8659 to 7575). In ALSPAC only we investigated BMI at 10 and 15 years (N = 4476 to 4112) and dual-energy X-ray absorptiometry (DXA) determined fat mass index (FMI) from age 10-18 years (N = 2659 to 3855). We compared MR results from several PRS, calculated from maternal non-transmitted alleles at between 29 and 80,939 single nucleotide polymorphisms (SNPs). RESULTS: MV and MR consistently showed a positive association between maternal BMI and BW, supporting a moderate causal effect. For adiposity at most older ages, although MV estimates indicated a strong positive association, MR estimates did not support a causal effect. For the PRS with few SNPs, MR estimates were statistically consistent with the null, but had wide confidence intervals so were often also statistically consistent with the MV estimates. In contrast, the largest PRS yielded MR estimates with narrower confidence intervals, providing strong evidence that the true causal effect on adolescent adiposity is smaller than the MV estimates (Pdifference = 0.001 for 15-year BMI). This suggests that the MV estimates are affected by residual confounding, therefore do not provide an accurate indication of the causal effect size. CONCLUSIONS: Our results suggest that higher maternal pre-/early-pregnancy BMI is not a key driver of higher adiposity in the next generation. Thus, they support interventions that target the whole population for reducing overweight and obesity, rather than a specific focus on women of reproductive age