Coupling the topological defect phase to the extrinsic curvature in nematic shells.

In two dimensional nematics, topological defects are point like singularities with both a charge and a phase. We study the topological defects within curved nematic textures on the surface of a cylinder. This allows us to isolate the effect of extrinsic curvature on the structure of the topological defect. By minimizing the energy associated with distortions in the nematic director around the core of a defect, we show that the phase of the topological defect is coupled to the orientation of the cylinder. This coupling depends on the relative energetic cost associated with splay, bend and twist distortions of the nematic director. We identify a bistability in the phase of the defects when twist deformations dominate. Finally, we show a similar effect for integer charge topological defects.

Lost in Time: Temporal Monitoring Elicits Clinical Decrements in Sustained Attention Post-Stroke.

OBJECTIVES: Mental fatigue, 'brain fog', and difficulties maintaining engagement are commonly reported issues in a range of neurological and psychiatric conditions. Traditional sustained attention tasks commonly measure this capacity as the ability to detect target stimuli based on sensory features in the auditory or visual domains. However, with this approach, discrete target stimuli may exogenously capture attention to aid detection, thereby masking deficits in the ability to endogenously sustain attention over time. METHODS: To address this, we developed the Continuous Temporal Expectancy Task (CTET) where individuals continuously monitor a stream of patterned stimuli alternating at a fixed temporal interval (690 ms) and detect an infrequently occurring target stimulus defined by a prolonged temporal duration (1020 ms or longer). As such, sensory properties of target and non-target stimuli are perceptually identical and differ only in temporal duration. Using the CTET, we assessed stroke survivors with unilateral right hemisphere damage (N = 14), a cohort in which sustained attention deficits have been extensively reported. RESULTS: Stroke survivors had overall lower target detection accuracy compared with neurologically healthy age-matched older controls (N = 18). Critically, stroke survivors performance was characterised by significantly steeper within-block performance decrements, which occurred within short temporal windows (˜3 ½ min), and were restored by the break periods between blocks. CONCLUSIONS: These findings suggest that continuous temporal monitoring taxes sustained attention processes to capture clinical deficits in this capacity over time, and outline a precise measure of the endogenous processes hypothesised to underpin sustained attention deficits following right hemisphere stroke.

Orientational Correlations in Active and Passive Nematic Defects.

We investigate the emergence of orientational order among +1/2 disclinations in active nematic liquid crystals. Using a combination of theoretical and experimental methods, we show that +1/2 disclinations have short-range antiferromagnetic alignment, as a consequence of the elastic torques originating from their polar structure. The presence of intermediate -1/2 disclinations, however, turns this interaction from antialigning to aligning at scales that are smaller than the typical distance between like-sign defects. No long-range orientational order is observed. Strikingly, these effects are insensitive to material properties and qualitatively similar to what is found for defects in passive nematic liquid crystals.

Properties of twisted topological defects in 2D nematic liquid crystals.

Topological defects are one of the most conspicuous features of liquid crystals. In two dimensional nematics, they have been shown to behave effectively as particles with both charge and orientation, which dictate their interactions. Here, we study "twisted" defects that have a radially dependent orientation. We find that twist can be partially relaxed through the creation and annihilation of defect pairs. By solving the equations for defect motion and calculating the forces on defects, we identify four distinct elements that govern the relative relaxational motion of interacting topological defects, namely attraction, repulsion, co-rotation and co-translation. The interaction of these effects can lead to intricate defect trajectories, which can be controlled by setting relevant timescales.

Activity Driven Orientational Order in Active Nematic Liquid Crystals on an Anisotropic Substrate.

We investigate the effect of an anisotropic substrate on the turbulent dynamics of a simulated two-dimensional active nematic. This is introduced as an anisotropic friction and an effective anisotropic viscosity, with the orientation of the anisotropy being defined by the substrate. In this system, we observe the emergence of global nematic order of topological defects that is controlled by the degree of anisotropy in the viscosity and the magnitude of the active stress. No global defect alignment is seen in passive liquid crystals with anisotropic viscosity or friction confirming that ordering is driven by the active stress. We then closely examine the active flow generated by a single defect to show that the net kinetic energy of the flow is dependent on the orientation of the defect relative to the substrate, resulting in a torque on the defect to align it with the anisotropy in the substrate.

Geometrical Control of Active Turbulence in Curved Topographies.

We investigate the turbulent dynamics of a two-dimensional active nematic liquid crystal constrained to a curved surface. Using a combination of hydrodynamic and particle-based simulations, we demonstrate that the fundamental structural features of the fluid, such as the topological charge density, the defect number density, the nematic order parameter, and defect creation and annihilation rates, are approximately linear functions of the substrate Gaussian curvature, which then acts as a control parameter for the chaotic flow. Our theoretical predictions are then compared with experiments on microtubule-kinesin suspensions confined on toroidal droplets, finding excellent qualitative agreement.

Cellular geometry controls the efficiency of motile sperm aggregates.

Sperm that swim collectively to the fertilization site have been observed across several vertebrate and invertebrate species, with groups ranging in size from sperm pairs to massive aggregates containing hundreds of cells. Although the molecular mechanisms that regulate sperm-sperm adhesion are still unclear, aggregation can enhance sperm motility and thus offer a fertilization advantage. Here, we report a thorough computational investigation on the role of cellular geometry in the performance of sperm aggregates. The sperm head is modelled as a persistent random walker characterized by a non-trivial three-dimensional shape and equipped with an adhesive region where cell-cell binding occurs. By considering both, a simple parametric head shape and a computer reconstruction of a real head shape based on morphometric data, we demonstrate that the geometry of the head and the structure of the adhesive region crucially affects both the stability and motility of the aggregates. Our analysis further suggests that the apical hook commonly found in the sperm of muroid rodents might serve to shield portions of the adhesive region and promote efficient alignment of the velocities of the interacting cells.

Microbial metabolism directly affects trace gases in (sub) polar snowpacks.

Concentrations of trace gases trapped in ice are considered to develop uniquely from direct snow/atmosphere interactions at the time of contact. This assumption relies upon limited or no biological, chemical or physical transformations occurring during transition from snow to firn to ice; a process that can take decades to complete. Here, we present the first evidence of environmental alteration due to in situ microbial metabolism of trace gases (methyl halides and dimethyl sulfide) in polar snow. We collected evidence for ongoing microbial metabolism from an Arctic and an Antarctic location during different years. Methyl iodide production in the snowpack decreased significantly after exposure to enhanced UV radiation. Our results also show large variations in the production and consumption of other methyl halides, including methyl bromide and methyl chloride, used in climate interpretations. These results suggest that this long-neglected microbial activity could constitute a potential source of error in climate history interpretations, by introducing a so far unappreciated source of bias in the quantification of atmospheric-derived trace gases trapped within the polar ice caps.

Influenza as a trigger for cardiovascular disease: An investigation of serotype, subtype and geographic location.

BACKGROUND: Seasonal peaks of influenza and cardiovascular disease tend to coincide. Many excess deaths may be triggered by influenza, and the severity of this effect may vary with the virulence of the circulating influenza strain and host susceptibility. We aimed to explore the association between hospital admissions for influenza and/or pneumonia (IP) and acute myocardial infarction (AMI) or ischaemic heart disease (IHD) in Queensland, Australia, taking into account temporal and spatial variation of influenza virus type and subtype in 2007, 2008 and 2009. METHODS: This ecological study at Statistical Subdivision level (SSD, n=38) used linked patient-level data. For each study year, Standardized Morbidity Ratios (SMRs) were calculated for hospital admissions with diagnoses of IP, AMI and IHD. We investigated the associations between IP and AMI or IHD using spatial autoregressive modelling, adjusting for socio-demographic factors. RESULTS: Spatial autocorrelation was detected in SMRs, possibly reflecting underlying social and behavioural risk factors, but consistent with infectious disease spread. SMRs for IP were consistently predictive of SMRs for AMI and IHD when adjusted for socioeconomic status, population density and per cent Indigenous population (coefficient: 0.707, 95% confidence interval (CI): 0.318 - 1.096; 0.553, 0.222 - 0.884; 0.598, 0.307 - 0.888 and 1.017, 0.711 - 1.323; 0.650, 0.342 - 0.958; 1.031, 0.827 - 1.236) in 2007, 2008 and 2009, respectively. CONCLUSIONS: This ecological study provides further evidence that severe respiratory infections may trigger the onset of cardiovascular events, implicating the influenza virus as a contributing factor.

Microbiology: lessons from a first attempt at Lake Ellsworth.

During the attempt to directly access, measure and sample Subglacial Lake Ellsworth in 2012-2013, we conducted microbiological analyses of the drilling equipment, scientific instrumentation, field camp and natural surroundings. From these studies, a number of lessons can be learned about the cleanliness of deep Antarctic subglacial lake access leading to, in particular, knowledge of the limitations of some of the most basic relevant microbiological principles. Here, we focus on five of the core challenges faced and describe how cleanliness and sterilization were implemented in the field. In the light of our field experiences, we consider how effective these actions were, and what can be learnt for future subglacial exploration missions. The five areas covered are: (i) field camp environment and activities, (ii) the engineering processes surrounding the hot water drilling, (iii) sample handling, including recovery, stability and preservation, (iv) clean access methodologies and removal of sample material, and (v) the biodiversity and distribution of bacteria around the Antarctic. Comparisons are made between the microbiology of the Lake Ellsworth field site and other Antarctic systems, including the lakes on Signy Island, and on the Antarctic Peninsula at Lake Hodgson. Ongoing research to better define and characterize the behaviour of natural and introduced microbial populations in response to deep-ice drilling is also discussed. We recommend that future access programmes: (i) assess each specific local environment in enhanced detail due to the potential for local contamination, (ii) consider the sterility of the access in more detail, specifically focusing on single cell colonization and the introduction of new species through contamination of pre-existing microbial communities, (iii) consider experimental bias in methodological approaches, (iv) undertake in situ biodiversity detection to mitigate risk of non-sample return and post-sample contamination, and (v) address the critical question of how important these microbes are in the functioning of Antarctic ecosystems.

Emergent behavioural phenotypes of swarming models revealed by mimicking a frustrated anti-ferromagnet.

Self-propelled particle (SPP) models are often compared with animal swarms. However, the collective animal behaviour observed in experiments often leaves considerable unconstrained freedom in the structure of a proposed model. Essentially, multiple models can describe the observed behaviour of animal swarms in simple environments. To tackle this degeneracy, we study swarms of SPPs in non-trivial environments as a new approach to distinguish between candidate models. We restrict swarms of SPPs to circular (periodic) channels where they polarize in one of two directions (like spins) and permit information to pass through windows between neighbouring channels. Co-alignment between particles then couples the channels (anti-ferromagnetically) so that they tend to counter-rotate. We study channels arranged to mimic a geometrically frustrated anti-ferromagnet and show how the effects of this frustration allow us to better distinguish between SPP models. Similar experiments could therefore improve our understanding of collective motion in animals. Finally, we discuss how the spin analogy can be exploited to construct universal logic gates, and therefore swarming systems that can function as Turing machines.

Entrance and propagation pattern of high-frequency electrical currents in biological tissues as applied to fractional skin rejuvenation using penetrating electrodes.

BACKGROUND: Fractional resurfacing of the skin using radiofrequency devices has been used for collagen remodeling and rejuvenation. OBJECTIVES: To determine how radiofrequency current enters and propagates through tissue, and the pattern of the resulting effect. MATERIALS AND METHODS: An electrosurgical device with a 0.4 MHz frequency output was used as the source of radiofrequency current. Current was applied via a metallic needle introduced into a large piece of cow liver, with different amounts of energy delivered at multiple points. Cross-sections of the liver were then studied for tissue effect. RESULTS: Thermal coagulation of tissue started from the tip of the electrode. With higher energy, a rim of coagulated tissue formed around the entire length of the needle. This rim of coagulated tissue was thicker around the tip of the electrode. CONCLUSION: Radiofrequency currents have a tendency to move toward the center of the bulk of tissue. When an electrode of a fractional radiofrequency device enters the skin, maximum heating effect will be around the tip of the electrode in the dermis. This phenomenon can preserve epidermis from injury during dermal heating, reducing post-procedural skin surface side effects seen with many skin rejuvenation procedures.

The Glucocorticoid-induced leucine zipper (GILZ) Is essential for spermatogonial survival and spermatogenesis.

Spermatogenesis relies on the precise regulation of the self-renewal and differentiation of spermatogonia to provide a continuous supply of differentiating germ cells. The understanding of the cellular pathways regulating this equilibrium remains unfortunately incomplete. This investigation aimed to elucidate the testicular and ovarian functions of the glucocorticoid-induced leucine zipper protein (GILZ) encoded by the X-linked Tsc22d3 (Gilz) gene. We found that GILZ is specifically expressed in the cytoplasm of proliferating spermatogonia and preleptotene spermatocytes. While Gilz mutant female mice were fully fertile, constitutive or male germ cell-specific ablation of Gilz led to sterility due to a complete absence of post-meiotic germ cells and mature spermatozoa. Alterations were observed as early as postnatal day 5 during the first spermatogenic wave and included extensive apoptosis at the spermatogonial level and meiotic arrest in the mid-late zygotene stage. Overall, these data emphasize the essential role played by GILZ in mediating spermatogonial survival and spermatogenesis.

Control of Mycobacterium tuberculosis growth by activated natural killer cells.

We characterized the underlying mechanisms by which glutathione (GSH)-enhanced natural killer (NK) cells inhibit the growth of Mycobacterium tuberculosis (M. tb) inside human monocytes. We observed that in healthy individuals, treatment of NK cells with N-acetyl cysteine (NAC), a GSH prodrug in conjunction with cytokines such as interleukin (IL)-2 + IL-12, resulted in enhanced expression of NK cytotoxic ligands (FasL and CD40L) with concomitant stasis in the intracellular growth of M. tb. Neutralization of FasL and CD40L in IL-2 + IL-12 + NAC-treated NK cells resulted in abrogation in the growth inhibition of M. tb inside monocytes. Importantly, we observed that the levels of GSH are decreased significantly in NK cells derived from individuals with HIV infection compared to healthy subjects, and this decrease correlated with a several-fold increase in the growth of M. tb inside monocytes. This study describes a novel innate defence mechanism adopted by NK cells to control M. tb infection.

Electronic medical record reduces HIV medication refill response time and emergency refills in a Latino community clinic.

In May 2006, our community clinic, serving mainly indigent HIV+ Latinos, initiated an electronic medical record (EMR) system that transmitted refill requests and responses between the pharmacy's software to and from the EMR. Prior to this time, refill requests had been perceived as delayed at times due to system problems and pharmacies had responded by issuing emergency refills of antiretrovirals to prevent possible medication resistance and morbidity as may result from missed doses. The EMR service appeared to reduce response time and errors. HealthMatics EMR and the Internet service SureScripts, in cooperation with two MOMS pharmacies, were utilized. We compared the following data from before EMR initiation and after 10 months of use: number of emergency refills/28 days, response times of the clinic to refill requests and opinions of the pharmacists. The average refill response time decreased from 1.57 to 1.04 days (P < 0.004) from 2006 (n = 115) to 2007 (n = 217). Variance decreased from 3.53 to 1.73, respectively, between two same 28-day periods. Before EMR, one pharmacy felt the response times were worse than other clinics, but both perceived general improvement with EMR. The numbers of emergency refills per period were 88 and <1 respectively. In conclusion, with the utilization of EMR for medication refill requests, (1) there was a statistically significant decrease in emergency refill utilization, (2) there was a statistically significant improvement in the response time to a refill request, and (3) pharmacists perceived improvement in response times.

Akt2/PKBbeta-sensitive regulation of renal phosphate transport.

AIM: The protein kinase B (PKB)/Akt is known to stimulate the cellular uptake of glucose and amino acids. The kinase is expressed in proximal renal tubules. The present study explored the influence of Akt/PKB on renal tubular phosphate transport. METHODS: The renal phosphate transporter NaPi-IIa was expressed in Xenopus oocytes with or without PKB/Akt and Na(+) phosphate cotransport determined using dual electrode voltage clamp. Renal phosphate excretion was determined in Akt2/PKBbeta knockout mice (akt2(-/-)) and corresponding wild-type mice (akt2(+/+)). Transporter protein abundance was determined using Western blotting and phosphate transport by (32)P uptake into brush border membrane vesicles. RESULTS: The phosphate-induced current in NaPi-IIa-expressing Xenopus oocytes was significantly increased by the coexpression of Akt/PKB. Phosphate excretion [micromol per 24 h per g BW] was higher by 91% in akt2(-/-) than in akt2(+/+) mice. The phosphaturia of akt2(-/-) mice occurred despite normal transport activity and expression of the renal phosphate transporters NaPi-IIa, NaPi-IIc and Pit2 in the brush border membrane, a significantly decreased plasma PTH concentration (by 46%) and a significantly enhanced plasma 1,25-dihydroxyvitamin D(3) concentration (by 46%). Moreover, fractional renal Ca(2+) excretion was significantly enhanced (by 53%) and bone density significantly reduced (by 11%) in akt2(-/-) mice. CONCLUSIONS: Akt2/PKBbeta plays a role in the acute regulation of renal phosphate transport and thus contributes to the maintenance of phosphate balance and adequate mineralization of bone.

Altered arginine metabolism in the central nervous system (CNS) of the Cln3-/- mouse model of juvenile Batten disease.

BACKGROUND: Juvenile neuronal ceroid lipofuscinoses (JNCL) or juvenile Batten disease is a recessively inherited childhood neurodegenerative disorder resulting from a mutation in CLN3, which encodes a putative lysosomal protein of unknown function. AIM: Recent evidence suggests that a disruption in CLN3 function results in altered regulation of arginine transport into lysosomes, and may influence intracellular arginine levels. We sought to investigate the possible consequences of arginine dysregulation in the brain of the Cln3(-/-) mouse model of JNCL. METHODS: Using a combination of enzyme assays, metabolite profiling, quantitative reverse-transcription polymerase chain reaction and Western blotting, we analysed the activities and expression of enzymes involved in arginine metabolism in the cerebral cortex and cerebellum of Cln3(-/-) mice over several developmental time points. RESULTS: We report subtle, but significant changes in the activities of enzymes involved in the citrulline-NO recycling pathway, and altered regulation of neuronal nitric oxide synthase in the cortex and cerebellum of Cln3(-/-) mice. In addition, a significant decrease in arginine transport into cerebellar granule cells was observed, despite an apparent upregulation of the cationic amino acid transporter-1 transporter at the cell surface. Our results provide further evidence that CLN3 function and arginine homeostasis are intricately related, and that cellular mechanisms may act to compensate for the loss of this protein. CONCLUSIONS: This and other studies indicate that CLN3 dysfunction in JNCL may result in multiple disturbances in metabolism that together contribute to the pathophysiological processes underlying this disease.

Neurodevelopmental delay in the Cln3Deltaex7/8 mouse model for Batten disease.

Juvenile neuronal ceroid lipofuscinosis (JNCL), also known as Batten disease, is a fatal inherited neurodegenerative disorder. The major clinical features of this disease are vision loss, seizures and progressive cognitive and motor decline starting in childhood. Mutations in CLN3 are known to cause the disease, allowing the generation of mouse models that are powerful tools for JNCL research. In this study, we applied behavioural phenotyping protocols to test for early behavioural alterations in Cln3(Deltaex7/8) knock-in mice, a genetic model that harbours the most common disease-causing CLN3 mutation. We found delayed acquisition of developmental milestones, including negative geotaxis, grasping, wire suspension time and postural reflex in both homozygous and heterozygous Cln3(Deltaex7/8) preweaning pups. To further investigate the consequences of this neurodevelopmental delay, we studied the behaviour of juvenile mice and found that homozygous and heterozygous Cln3(Deltaex7/8) knock-in mice also exhibit deficits in exploratory activity. Moreover, when analysing motor behaviour, we observed severe motor deficits in Cln3(Deltaex7/8) homozygous mice, but only a mild impairment in motor co-ordination and ambulatory gait in Cln3(Deltaex7/8) heterozygous animals. This study reveals previously overlooked behaviour deficits in neonate and young adult Cln3(Deltaex7/8) mice indicating neurodevelopmental delay as a putative novel component of JNCL.