The intrinsic stiffness of human trabecular meshwork cells increases with senescence.

Dysfunction of the human trabecular meshwork (HTM) plays a central role in the age-associated disease glaucoma, a leading cause of irreversible blindness. The etiology remains poorly understood but cellular senescence, increased stiffness of the tissue, and the expression of Wnt antagonists such as secreted frizzled related protein-1 (SFRP1) have been implicated. However, it is not known if senescence is causally linked to either stiffness or SFRP1 expression. In this study, we utilized in vitro HTM senescence to determine the effect on cellular stiffening and SFRP1 expression. Stiffness of cultured cells was measured using atomic force microscopy and the morphology of the cytoskeleton was determined using immunofluorescent analysis. SFRP1 expression was measured using qPCR and immunofluorescent analysis. Senescent cell stiffness increased 1.88±0.14 or 2.57±0.14 fold in the presence or absence of serum, respectively. This was accompanied by increased vimentin expression, stress fiber formation, and SFRP1 expression. In aggregate, these data demonstrate that senescence may be a causal factor in HTM stiffening and elevated SFRP1 expression, and contribute towards disease progression. These findings provide insight into the etiology of glaucoma and, more broadly, suggest a causal link between senescence and altered tissue biomechanics in aging-associated diseases

Biotic interactions in soil and dung shape parasite transmission in temperate ruminant systems : An integrative framework

ACKNOWLEDGMENTS We are thankful to QUADRAT doctoral training partnership for providing the opportunity to complete this work. This work was supported by a QUADRAT doctoral training program PhD studentship from UK Research and Innovation, via the Natural Environment Research Council. Natural Environment Research Council (NERC). Grant Number: NE/S007377/1 UKRIPeer reviewe

Proton and cadmium adsorption by the archaeon Thermococcus zilligii: Generalising the contrast between thermophiles and mesophiles as sorbents

Adsorption by microorganisms can play a significant role in the fate and transport of metals in natural systems. Surface complexation models (SCMs) have been applied extensively to describe metal adsorption by mesophilic bacteria, and several recent studies have extended this framework to thermophilic bacteria. We conduct acid-base titrations and batch experiments to characterise proton and Cd adsorption onto the thermophilic archaeon Thermococcus zilligii. The experimental data and the derived SCMs indicate that the archaeon displays significantly lower overall sorption site density compared to previously studied thermophilic bacteria such Anoxybacillus flavithermus, Geobacillus stearothermophilus, G. thermocatenulatus, and Thermus thermophilus. The thermophilic bacteria and archaea display lower sorption site densities than the mesophilic microorganisms that have been studied to date, which points to a general pattern of total concentration of cell wall adsorption sites per unit biomass being inversely correlated to growth temperature

A Foundational Population Genetics Investigation of the Sexual Systems of Solanum (Solanaceae) in the Australian Monsoon Tropics Suggests Dioecious Taxa May Benefit from Increased Genetic Admixture via Obligate Outcrossing

Solanum section Leptostemonum is an ideal lineage to test the theoretical framework regarding proposed evolutionary benefits of outcrossing sexual systems in comparison to cosexuality. Theoretically, non-cosexual taxa should support more genetic diversity within populations, experience less inbreeding, and have less genetic structure due to a restricted ability to self-fertilize. However, many confounding factors present challenges for a confident inference that inherent differences in sexual systems influence observed genetic patterns among populations. This study provides a foundational baseline of the population genetics of several species of different sexual systems with the aim of generating hypotheses of any factor—including sexual system—that influences genetic patterns. Importantly, results indicate that dioecious S. asymmetriphyllum maintains less genetic structure and greater admixture among populations than cosexual S. raphiotes at the same three locations where they co-occur. This suggests that when certain conditions are met, the evolution of dioecy may have proceeded as a means to avoid genetic consequences of self-compatibility and may support hypotheses of benefits gained through differential resource allocation partitioned across sexes. Arguably, the most significant finding of this study is that all taxa are strongly inbred, possibly reflective of a shared response to recent climate shifts, such as the increased frequency and intensity of the region’s fire regime

Biomechanical, ultrastructural, and electrophysiological characterization of the non-human primate experimental glaucoma model.

Laser-induced experimental glaucoma (ExGl) in non-human primates (NHPs) is a common animal model for ocular drug development. While many features of human hypertensive glaucoma are replicated in this model, structural and functional changes in the unlasered portions of trabecular meshwork (TM) of laser-treated primate eyes are understudied. We studied NHPs with ExGl of several years duration. As expected, ExGl eyes exhibited selective reductions of the retinal nerve fiber layer that correlate with electrophysiologic measures documenting a link between morphologic and elctrophysiologic endpoints. Softening of unlasered TM in ExGl eyes compared to untreated controls was observed. The degree of TM softening was consistent, regardless of pre-mortem clinical findings including severity of IOP elevation, retinal nerve fiber layer thinning, or electrodiagnostic findings. Importantly, this softening is contrary to TM stiffening reported in glaucomatous human eyes. Furthermore, microscopic analysis of unlasered TM from eyes with ExGl demonstrated TM thinning with collapse of Schlemm's canal; and proteomic analysis confirmed downregulation of metabolic and structural proteins. These data demonstrate unexpected and compensatory changes involving the TM in the NHP model of ExGl. The data suggest that compensatory mechanisms exist in normal animals and respond to elevated IOP through softening of the meshwork to increase outflow

Attention and motor profiles in children with developmental coordination disorder: A neuropsychological and neuroimaging investigation

AIM: This study aimed to (1) quantify attention and executive functioning in children with developmental coordination disorder (DCD), (2) assess whether some children with DCD are more likely to show attention difficulties, and (3) characterize brain correlates of motor and attention deficits. METHOD: Fifty-three children (36 with DCD and 17 without) aged 8 to 10 years underwent T1-weighted and diffusion-weighted magnetic resonance imaging, and standardized attention and motor assessments. Parents completed questionnaires of executive functioning and symptoms of inattention and hyperactivity. We assessed regional cortical thickness and surface area, and cerebellar, callosal, and primary motor tract structure. RESULTS: Analyses of covariance and one-sample t-tests identified impaired attention, non-motor processing speed, and executive functioning in children with DCD, yet partial Spearman's rank correlation coefficients revealed these were unrelated to one another or the type or severity of the motor deficit. Robust regression analyses revealed that cortical morphology in the posterior cingulate was associated with both gross motor skills and inattentive symptoms in children with DCD, while gross motor skills were also associated with left corticospinal tract (CST) morphology. INTERPRETATION: Children with DCD may benefit from routine attention and hyperactivity assessments. Alterations in the posterior cingulate and CST may be linked to impaired forward modelling during movements in children with DCD. Overall, alterations in these regions may explain the high rate of non-motor impairments in children with DCD

Cues and knowledge structures used by mental-health professionals when making risk assessments

Background: Research into mental-health risks has tended to focus on epidemiological approaches and to consider pieces of evidence in isolation. Less is known about the particular factors and their patterns of occurrence that influence clinicians’ risk judgements in practice. Aims: To identify the cues used by clinicians to make risk judgements and to explore how these combine within clinicians’ psychological representations of suicide, self-harm, self-neglect, and harm to others. Method: Content analysis was applied to semi-structured interviews conducted with 46 practitioners from various mental-health disciplines, using mind maps to represent the hierarchical relationships of data and concepts. Results: Strong consensus between experts meant their knowledge could be integrated into a single hierarchical structure for each risk. This revealed contrasting emphases between data and concepts underpinning risks, including: reflection and forethought for suicide; motivation for self-harm; situation and context for harm to others; and current presentation for self-neglect. Conclusions: Analysis of experts’ risk-assessment knowledge identified influential cues and their relationships to risks. It can inform development of valid risk-screening decision support systems that combine actuarial evidence with clinical expertise

Coupling electron capture dissociation and the modified Kendrick mass defect for sequencing of a poly(2-ethyl-2-oxazoline) polymer

With increasing focus on the structural elucidation of polymers, advanced tandem mass spectrometry techniques will play a crucial role in the characterization of these compounds. In this contribution, synthesis and analysis of methyl initiated and xan-thate terminated poly (2-ethyl-2-oxazoline) using Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry was achieved. Electron capture dissociation (ECD) produced full end group characterization as well as back bone fragmentation including complete sequence coverage of the polymer. A method of fragment ion characterization is also presented with the use of the high resolution modified Kendrick mass defect plots as a means of grouping fragments from the same fragmentation pathways together. This type of data processing is applicable to all tandem mass spectrometry techniques for polymer analysis but is made more effective with high mass accuracy methods. ECD FT-ICR MS demonstrates its promising role as a structural characterization technique for polyoxazoline species