Investigation of the limits of nanoscale filopodial interactions

Mesenchymal stem cells are sensitive to changes in feature height, order and spacing. We had previously noted that there was an inverse relationship between osteoinductive potential and feature height on 15-, 55- and 90 nm-high titania nanopillars, with 15 nm-high pillars being the most effective substrate at inducing osteogenesis of human mesenchymal stem cells. The osteoinductive effect was somewhat diminished by decreasing the feature height to 8 nm, however, which suggested that there was a cut-off point, potentially associated with a change in cell–nanofeature interactions. To investigate this further, in this study, a scanning electron microscopy/three-dimensional scanning electron microscopy approach was used to examine the interactions between mesenchymal stem cells and the 8 and 15 nm nanopillared surfaces. As expected, the cells adopted a predominantly filopodial mode of interaction with the 15 nm-high pillars. Interestingly, fine nanoscale membrane projections, which we have termed ‘nanopodia,’ were also employed by the cells on the 8 nm pillars, and it seems that this is analogous to the cells ‘clinging on with their fingertips’ to this scale of features

Labour efficiency on-farm

End of project reportImprovements in milking efficiency have a greater influence than any other aspect of the dairy farmers work on overall farm labour inputs (Whipp, 1992). In order to facilitate the examination of milking process labour inputs, the milking process may be divided into the following three components: herding pre and post milking (transfer of cows to and from the milking parlour); milking (milking tasks / work routines within the parlour); and washing (washing of milking machine and yard). Meanwhile, within milking specifically, the number of cows milked per operator per hour is the best measure of both the performance of the operator and the milking installation (Clough, 1978). This is affected by the following three factors: the milking times of the cows, the number and arrangement of the milking units, and the operator’s work routine (Whipp, 1992). The addition of extra milking units will only increase milking performance if the operator has idle time during milking (Hansen, 1999)

Brief Note: Characterization of Hydrophobic Stream Bacteria Based on Adhesion to n-Octane

Author Institution: Department of Biological Sciences, Kent State UniversityThe purpose of this study was to characterize stream bacterial communities based on cell surface hydrophobicity. Because hydrophobicity is related to adhesion we hypothesized that more hydrophobic bacteria would be found on solid surfaces than in water. Water, rock, and sediment from two northeastern Ohio streams were sampled and bacteria were plated on modified nutrient agar. Hydrophobicity was determined by measuring adherence to n-octane. No difference was found in the proportion of hydrophobic bacteria among habitats. Two hydrophobic isolates were identified as Sphingomonas paucimobilis and Chryseomonas luteola. A large proportion of hydrophobic bacteria were gram positive and urease positive; none were gelatinase positive. More hydrophobic than hydrophilic bacteria were able to grow using manatose or malatose as the only carbon source. These physiological differences indicate that hydrophobic bacteria may be able to utilize resources not available to hydrophilic bacteria

Molecular and cellular analysis of topography-induced mechanotransduction

Edited Abstract: Mechanotransduction is the process by which cells convert mechanical stimuli into an adaptive gene- and protein-level response, via signalling cascades or direct physical effects of the cytoskeleton on the nucleus, and appropriate mechanosignalling is crucial for tissue development and function. Most techniques currently used to study cellular mechanoresponses are relatively damaging to the cells. In contrast, topographically structured substrates, such as microgrooves, have great potential for use as non-invasive mechanostimuli. In this study, quartz microgrooved substrata (2 μm depth x 25 μm pitch) were used as platforms for the confinement and alignment of cells. A multi-layered approach was adopted to begin to integrate the changes induced by the topographical mechanostimulus at the chromosome, small RNA, transcript, protein and structural levels. Together, the results provide insight into multiple facets of topography-induced mechanotransduction, which should contribute to understanding of mechanotransduction and cell-material interactions

Critical perspectives on writing analytics

Writing Analytics focuses on the measurement and analysis of written texts for the purpose of understanding writing processes and products, in their educational contexts, and improving the teaching and learning of writing. This workshop adopts a critical, holistic perspective in which the definition of "the system" and "success" is not restricted to IR metrics such as precision and recall, but recognizes the many wider issues that aid or obstruct analytics adoption in educational settings, such as theoretical and pedagogical grounding, usability, user experience, stakeholder design engagement, practitioner development, organizational infrastructure, policy and ethics

Pathophysiology, diagnosis, and management of neuroinflammation in covid-19

Although neurological complications of SARS-CoV-2 infection are relatively rare, their potential long term morbidity and mortality have a significant impact, given the large numbers of infected patients. Covid-19 is now in the differential diagnosis of a number of common neurological syndromes including encephalopathy, encephalitis, acute demyelinating encephalomyelitis, stroke, and Guillain-Barré syndrome. Physicians should be aware of the pathophysiology underlying these presentations to diagnose and treat patients rapidly and appropriately. Although good evidence has been found for neurovirulence, the neuroinvasive and neurotropic potential of SARS-CoV-2 is limited. The pathophysiology of most complications is immune mediated and vascular, or both. A significant proportion of patients have developed long covid, which can include neuropsychiatric presentations. The mechanisms of long covid remain unclear. The longer term consequences of infection with covid-19 on the brain, particularly in terms of neurodegeneration, will only become apparent with time and long term follow-up

The Interaction of 3C401 with the Surrounding Intracluster Medium

We present an observation of the radio-galaxy 3C401 and the surrounding intracluster medium (ICM) of its host galaxy cluster by the Chandra X-ray Observatory. This luminous radio-galaxy is notable in that it has characteristics intermediate between the FRI and FRII morphologies. We clearly detect point-like emission coincident with the radio-core of 3C401, although the spatial resolution of even Chandra is only 2kpc at the distance of 3C401 (z=0.201) and so the possibility remains that this is a dense (and rapidly cooling) thermal gaseous core in the center of the ICM atmosphere. Strong departures from spherical symmetry in the central 10-20kpc of the ICM clearly suggest interaction between the ICM and the radio-lobes of 3C401. A central X-ray bar probably results from the evacuation of two ICM cavities by the expanding radio lobes. Beyond these central regions, the cluster possesses a flatter profile than many clusters of comparable mass suggesting the importance of ICM heating and entropy injection by 3C401. We detect an interesting cross-like structure in the ICM on 100kpc scales. We speculate that this could be a radio-galaxy induced disturbance corresponding to a time when 3C401 was substantially more powerful. A particularly exciting possibility is that this cross-like structure corresponds to a large scale global g-mode oscillation excited by a past outburst of 3C401.Comment: 7 pages, 5 postscript figures. Accepted for publication in MNRA

A novel p38α MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model

<p>Abstract</p> <p>Background</p> <p>An accumulating body of evidence is consistent with the hypothesis that excessive or prolonged increases in proinflammatory cytokine production by activated glia is a contributor to the progression of pathophysiology that is causally linked to synaptic dysfunction and hippocampal behavior deficits in neurodegenerative diseases such as Alzheimer's disease (AD). This raises the opportunity for the development of new classes of potentially disease-modifying therapeutics. A logical candidate CNS target is p38α MAPK, a well-established drug discovery molecular target for altering proinflammatory cytokine cascades in peripheral tissue disorders. Activated p38 MAPK is seen in human AD brain tissue and in AD-relevant animal models, and cell culture studies strongly implicate p38 MAPK in the increased production of proinflammatory cytokines by glia activated with human amyloid-beta (Aβ) and other disease-relevant stressors. However, the vast majority of small molecule drugs do not have sufficient penetrance of the blood-brain barrier to allow their use as <it>in vivo </it>research tools or as therapeutics for neurodegenerative disorders. The goal of this study was to test the hypothesis that brain p38α MAPK is a potential <it>in vivo </it>target for orally bioavailable, small molecules capable of suppressing excessive cytokine production by activated glia back towards homeostasis, allowing an improvement in neurologic outcomes.</p> <p>Methods</p> <p>A novel synthetic small molecule based on a molecular scaffold used previously was designed, synthesized, and subjected to analyses to demonstrate its potential <it>in vivo </it>bioavailability, metabolic stability, safety and brain uptake. Testing for <it>in vivo </it>efficacy used an AD-relevant mouse model.</p> <p>Results</p> <p>A novel, CNS-penetrant, non-toxic, orally bioavailable, small molecule inhibitor of p38α MAPK (MW01-2-069A-SRM) was developed. Oral administration of the compound at a low dose (2.5 mg/kg) resulted in attenuation of excessive proinflammatory cytokine production in the hippocampus back towards normal in the animal model. Animals with attenuated cytokine production had reductions in synaptic dysfunction and hippocampus-dependent behavioral deficits.</p> <p>Conclusion</p> <p>The p38α MAPK pathway is quantitatively important in the Aβ-induced production of proinflammatory cytokines in hippocampus, and brain p38α MAPK is a viable molecular target for future development of potential disease-modifying therapeutics in AD and related neurodegenerative disorders.</p

Dynamic surfaces for the study Of mesenchymal stem cell growth through adhesion regulation

Out of their niche environment, adult stem cells, such as mesenchymal stem cells (MSCs), spontaneously differentiate. This makes both studying these important regenerative cells and growing large numbers of stem cells for clinical use challenging. Traditional cell culture techniques have fallen short of meeting this challenge, but materials science offers hope. In this study, we have used emerging rules of managing adhesion/cytoskeletal balance to prolong MSC cultures by fabricating controllable nanoscale cell interfaces using immobilized peptides that may be enzymatically activated to change their function. The surfaces can be altered (activated) at will to tip adhesion/cytoskeletal balance and initiate differentiation, hence better informing biological mechanisms of stem cell growth. Tools that are able to investigate the stem cell phenotype are important. While large phenotypical differences, such as the difference between an adipocyte and an osteoblast, are now better understood, the far more subtle differences between fibroblasts and MSCs are much harder to dissect. The development of technologies able to dynamically navigate small differences in adhesion are critical in the race to provide regenerative strategies using stem cells