Virtual reality for biochemistry education: the cellular factory.

Virtual Reality (VR) involves the coupling of visual communication hardware and software. The technology is capable of offering transformative educational practice and is increasingly being adopted within the biochemistry domain to better understand complex biochemical processes. This article documents a pilot study for the efficacy of VR in biochemistry education at undergraduate university level, focusing on the citric acid cycle: a central process for extracting energy in most cellular life forms. 10 participants were equipped with a VR headset and electrodermal activity (EDA) sensors, then immersed within a digital environment where they were able to learn the 8 main steps of the citric acid cycle within a virtual lab by completing 8 levels of activity. Post and pre surveys were taken, along with EDA readings throughout the students' interaction with VR. Research findings support the hypothesis that VR increase students' understanding, particularly if students feel engaged, stimulated and intend to use the technology. Moreover, EDA analysis indicated that the majority of participants demonstrate enhanced engagement in the education-based VR-experience as measured by elevated levels of skin conductance, a marker for autonomic arousal and a measure of engagement in an activity.

Towards Computational Modeling of Ligand Binding to the ILPR G-Quadruplex.

Using a combination of unconstrained and constrained molecular dynamics simulations, we have evaluated the binding affinities between two porphyrin derivatives (TMPyP4 and TEGPy) and the G-quadruplex (G4) of a DNA fragment modeling the insulin-linked polymorphic region (ILPR). Refining a well-established potential of mean force (PMF) approach to selections of constraints based on root-mean-square fluctuations results in an excellent agreement between the calculated and observed absolute free binding energy of TMPyP4. The binding affinity of IPLR-G4 toward TEGPy is predicted to be higher than that toward TMPyP4 by 2.5 kcal/mol, which can be traced back to stabilization provided by the polyether side chains of TMPyP4 that can nestle into the grooves of the quadruplex and form hydrogen bonds through the ether oxygen atoms. Because our refined methodology can be applied to large ligands with high flexibility, the present research opens an avenue for further ligand design in this important area.

M3 Receptor Pathway Stimulates Rapid Transcription of the CB1 Receptor Activation through Calcium Signalling and the CNR1 Gene Promoter.

In this study, we have investigated a possible mechanism that enables CB1/M3 receptor cross-talk, using SH-SY5Y cells as a model system. Our results show that M3 receptor activation initiates signaling that rapidly upregulates the CNR1 gene, resulting in a greatly potentiated CB1 receptor response to agonists. Calcium homeostasis plays an essential intermediary role in this functional CB1/M3 receptor cross-talk. We show that M3 receptor-triggered calcium release greatly increases CB1 receptor expression via both transcriptional and translational activity, by enhancing CNR1 promoter activity. The co-expression of M3 and CB1 receptors in brain areas such as the nucleus accumbens and amygdala support the hypothesis that the altered synaptic plasticity observed after exposure to cannabinoids involves cross-talk with the M3 receptor subtype. In this context, M3 receptors and their interaction with the cannabinoid system at the transcriptional level represent a potential pharmacogenomic target not only for the develop of new drugs for addressing addiction and tolerance. but also to understand the mechanisms underpinning response stratification to cannabinoids.

"I had no idea the university offered" : The support needs of postgraduate taught students.

This article was migrated. The article was marked as recommended. Introduction Medical schools have a duty to support students to ensure they fulfil their potential. Relatively little is known about the generic, or therapeutic, support needs of postgraduate taught (PGT) students. This is an important gap to address given the literature suggests that "one size does not fit all". Thus, our aim was to explore and understand PGT support needs. Methods This was a qualitative research study using semi-structured focus groups, conducted in one UK university. We recruited medical and science undergraduates as well as PGT participants to get a sense of what was unique to the PGT student experience. Questions were drawn from the literature and local evaluation data. Discussions were audio-recorded and transcribed verbatim for inductive data coding and analysis. Results Six focus groups were conducted with 38 participants. Two main themes each with two sub-themes were identified: Communication (Practicalities; Fulfilled but not tailored) related to the transition into PGT, and Time and Contacts, related to managing the course. Discussion PGT students need to address non-academic, often practical, factors in a timely way to navigate university successfully. Knowing who to ask and informal supports are important. Poor and/or difficult-to-access institutional supports may leave PGT students vulnerable.

Four direct measurements of the fine-structure constant 13 billion years ago.

Observations of the redshift z = 7.085 quasar J1120+0641 are used to search for variations of the fine structure constant, α, over the redshift range 5.5 to 7.1. Observations at z = 7.1 probe the physics of the universe at only 0.8 billion years old. These are the most distant direct measurements of α to date and the first measurements using a near-IR spectrograph. A new AI analysis method is employed. Four measurements from the x-shooter spectrograph on the Very Large Telescope (VLT) constrain changes in a relative to the terrestrial value (α0). The weighted mean electromagnetic force in this location in the universe deviates from the terrestrial value by Δα/α = (α z - α0)/α0 = (-2.18 ± 7.27) × 10-5, consistent with no temporal change. Combining these measurements with existing data, we find a spatial variation is preferred over a no-variation model at the 3.9σ level.

The area of a rough black hole.

We investigate the consequences for the black hole area of introducing fractal structure for the horizon geometry. We create a three-dimensional spherical analogue of a 'Koch Snowflake' using a infinite diminishing hierarchy of touching spheres around the Schwarzschild event horizon. We can create a fractal structure for the horizon with finite volume and infinite (or finite) area. This is a toy model for the possible effects of quantum gravitational spacetime foam, with significant implications for assessments of the entropy of black holes and the universe, which is generally larger than in standard picture of black hole structure and thermodynamics, potentially by very considerable factors. The entropy of the observable universe today becomes S ≈ 10 120 ( 1 + Δ / 2 ) , where 0 ≤ Δ ≤ 1 , with Δ = 0 for a smooth spacetime structure and Δ = 1 for the most intricate. The Hawking lifetime of black holes is also reduced.

Szekeres universes with homogeneous scalar fields.

We consider the existence of an "inflaton" described by an homogeneous scalar field in the Szekeres cosmological metric. The gravitational field equations are reduced to two families of solutions which describe the homogeneous Kantowski-Sachs spacetime and an inhomogeneous FLRW(-like) spacetime with spatial curvature a constant. The main differences with the original Szekeres spacetimes containing only pressure-free matter are discussed. We investigate the stability of the two families of solution by studying the critical points of the field equations. We find that there exist stable solutions which describe accelerating spatially-flat FLRW geometries.

Reconstructions of the dark-energy equation of state and the inflationary potential.

We use a mathematical approach based on the constraints systems in order to reconstruct the equation of state and the inflationary potential for the inflaton field from the observed spectral indices for the density perturbations n s and the tensor to scalar ratio r. From the astronomical data, we can observe that the measured values of these two indices lie on a two-dimensional surface. We express these indices in terms of the Hubble slow-roll parameters and we assume that n s - 1 = h r . For the function h r , we consider three cases, where h r is constant, linear and quadratic, respectively. From this, we derive second-order equations whose solutions provide us with the explicit forms for the expansion scale-factor, the scalar-field potential, and the effective equation of state for the scalar field. Finally, we show that for there exist mappings which transform one cosmological solution to another and allow new solutions to be generated from existing ones.

Limits on the dependence of the fine-structure constant on gravitational potential from white-dwarf spectra.

We propose a new probe of the dependence of the fine-structure constant α on a strong gravitational field using metal lines in the spectra of white-dwarf stars. Comparison of laboratory spectra with far-UV astronomical spectra from the white-dwarf star G191-B2B recorded by the Hubble Space Telescope Imaging Spectrograph gives limits of Δα/α=(4.2±1.6)×10(-5) and (-6.1±5.8)×10(-5) from FeV and NiV spectra, respectively, at a dimensionless gravitational potential relative to Earth of Δφ≈5×10(-5). With better determinations of the laboratory wavelengths of the lines employed these results could be improved by up to 2 orders of magnitude.

Continent-wide tracking to determine migratory connectivity and tropical habitat associations of a declining aerial insectivore.

North American birds that feed on flying insects are experiencing steep population declines, particularly long-distance migratory populations in the northern breeding range. We determine, for the first time, the level of migratory connectivity across the range of a songbird using direct tracking of individuals, and test whether declining northern populations have higher exposure to agricultural landscapes at their non-breeding grounds in South America. We used light-level geolocators to track purple martins, Progne subis, originating from North American breeding populations, coast-to-coast (n = 95 individuals). We show that breeding populations of the eastern subspecies, P. s. subis, that are separated by ca. 2000 km, nevertheless have almost completely overlapping non-breeding ranges in Brazil. Most (76%) P. s. subis overwintered in northern Brazil near the Amazon River, not in the agricultural landscape of southern Brazil. Individual non-breeding sites had an average of 91 per cent forest and only 4 per cent agricultural ground cover within a 50 km radius, and birds originating from declining northern breeding populations were not more exposed to agricultural landscapes than stable southern breeding populations. Our results show that differences in wintering location and habitat do not explain recent trends in breeding population declines in this species, and instead northern populations may be constrained in their ability to respond to climate change.

New solution of the cosmological constant problems.

We extend the usual gravitational action principle by promoting the bare cosmological constant (CC) to a field which can take many possible values. Variation gives a new integral constraint equation for the classical value of the effective CC that dominates the wave function of the Universe. The expected value of the effective CC, is calculated from measurable quantities to be O(t(U)(-2)) as observed, where t(U) is the present age of the Universe in Planck units. This also leads to a falsifiable prediction for the observed spatial curvature parameter of Ω(k0) = -0.0055. Our proposal requires no fine-tunings or extra dark-energy fields but suggests a new view of time evolution.

Prediction and characterisation of a highly conserved, remote and cAMP responsive enhancer that regulates Msx1 gene expression in cardiac neural crest and outflow tract.

Double knockouts of the Msx1 and Msx2 genes in the mouse result in severe cardiac outflow tract malformations similar to those frequently found in newborn infants. Despite the known role of the Msx genes in cardiac formation little is known of the regulatory systems (ligand receptor, signal transduction and protein-DNA interactions) that regulate the tissue-specific expression of the Msx genes in mammals during the formation of the outflow tract. In the present study we have used a combination of multi-species comparative genomics, mouse transgenic analysis and in-situ hybridisation to predict and validate the existence of a remote ultra-conserved enhancer that supports the expression of the Msx1 gene in migrating mouse cardiac neural crest and the outflow tract primordia. Furthermore, culturing of embryonic explants derived from transgenic lines with agonists of the PKC and PKA signal transduction systems demonstrates that this remote enhancer is influenced by PKA but not PKC dependent gene regulatory systems. These studies demonstrate the efficacy of combining comparative genomics and transgenic analyses and provide a platform for the study of the possible roles of Msx gene mis-regulation in the aetiology of congenital heart malformation.

A highly conserved Wnt-dependent TCF4 binding site within the proximal enhancer of the anti-myogenic Msx1 gene supports expression within Pax3-expressing limb bud muscle precursor cells.

The product of the Msx1 gene is a potent inhibitor of muscle differentiation. Msx1 is expressed in muscle precursor cells of the limb bud that also express Pax3. It is thought that Msx1 may facilitate distal migration by delaying myogenesis in these cells. Despite the role played by Msx1 in inhibiting muscle differentiation, nothing is known of the mechanisms that support the expression of the Msx1 gene within limb bud muscle precursor cells. In the present study we have used a combination of comparative genomics, mouse transgenic analysis, in situ hybridisation and immunohistochemistry to identify a highly conserved and tissue-specific regulatory sub-domain within the previously characterised Msx1 gene proximal enhancer element that supports the expression of the Msx1 gene in Pax3-expressing mouse limb pre-muscle masses. Furthermore, using a combination of in situ hybridisation, in vivo ChIP assay and transgenic explant culture analysis we provide evidence that Msx1 expression in limb bud muscle precursor cells is dependent on the canonical Wnt/TCF signalling pathway that is important in muscle shape formation. The results of these studies provide evidence of a mechanistic link between the Wnt/TCF and the Msx1/Pax3/MyoD pathways within limb bud muscle precursor cells.

Presence of endocrine and exocrine markers in EGFP-positive cells from the developing pancreas of a nestin/EGFP mouse.

In order to purify and characterize nestin-positive cells in the developing pancreas a transgenic mouse was generated, in which the enhanced green fluorescent protein (EGFP) was driven by the nestin second intronic enhancer and upstream promoter. In keeping with previous studies on the distribution of nestin, EGFP was expressed in the developing embryo in neurones in the brain, eye, spinal cord, tail bud and glial cells in the small intestine. In the pancreas there was no detectable EGFP at embryonic day 11.5 (E11.5). EGFP expression appeared at E12.5 and increased in intensity through E14.5, E18.5 and post-natal day 1. Flow cytometry was used to quantify and purify the EGFP positive population in the E15.5 pancreas. The purified (96%) EGFP-expressing cells, which represent 20% of the total cell population, were shown by RT/PCR to express exocrine cell markers (amylase and P48) and endocrine cell markers (insulin 1, insulin 2, and Ngn3). They also expressed, at a lower level, PDX-1, Isl-1, and the islet hormones pancreatic polypeptide, glucagon and somatostatin as well as GLUT2, the stem cell marker ABCG2 and PECAM, a marker of endothelial cells. It was further shown by immunocytochemistry of the E15.5 pancreas that EGFP colocalised in separate subpopulations of cells that expressed nestin, insulin and amylase. These results support the conclusion that nestin expressing cells can give rise to both endocrine and exocrine cells. The ability to purify these putative progenitor cells may provide further insights into their properties and function.

Transcription factor cycling on the insulin promoter.

Using MIN6 beta-cells and chromatin immunoprecipitation (ChIP) assays, the chronological sequence of binding of MafA, E47/beta2 and PDX-1 to the insulin promoter in living beta-cells were investigated. All four factors were shown to bind to the mouse insulin 2 promoter in a cyclical manner with a periodicity of approximately 10-15 min. The cyclical binding of MafA, E47 and beta2 was largely unaffected by the glucose or insulin concentration in the media. However, the binding and cycling of PDX-1 was markedly abolished in low glucose (1 mM), and this was reversed in the presence of low concentrations of insulin.

Varying constants.

We review properties of theories for the variation of gravitation and fine structure 'constants'. We highlight some general features of the cosmological models that exist in these theories with reference to recent quasar data that are consistent with time variation in the fine structure constant since a redshift of 3.5. The behaviour of a simple class of varying-alpha cosmologies is outlined in the light of all the observational constraints.

Relative contribution of PDX-1, MafA and E47/beta2 to the regulation of the human insulin promoter.

The insulin promoter binds a number of tissue-specific and ubiquitous transcription factors. Of these, the homoeodomain protein PDX-1 (pancreatic duodenal homeobox factor-1), the basic leucine zipper protein MafA and the basic helix-loop-helix heterodimer E47/BETA2 (beta-cell E box transactivator 2; referred to here as beta2) bind to important regulatory sites. Previous studies have shown that PDX-1 can interact synergistically with E47 and beta2 to activate the rat insulin 1 promoter. The aim of the present study was to determine the relative contribution of PDX-1, MafA and E47/beta2 in regulating the human insulin promoter, and whether these factors could interact synergistically in the context of the human promoter. Mutagenesis of the PDX-1, MafA and E47/beta2 binding sites reduced promoter activity by 60, 74 and 94% respectively, in INS-1 beta-cells. In the islet glucagonoma cell line alphaTC1.6, overexpression of PDX-1 and MafA separately increased promoter activity approx. 2.5-3-fold, and in combination approx. 6-fold, indicating that their overall effect was additive. Overexpression of E47 and beta2 had no effect. In HeLa cells, PDX-1 stimulated the basal promoter by approx. 40-fold, whereas MafA, E47 and beta2 each increased activity by less than 2-fold. There was no indication of any synergistic effects on the human insulin promoter. On the other hand, the rat insulin 1 promoter and a mutated version of the human insulin promoter, in which the relevant regulatory elements were separated by the same distances as in the rat insulin 1 promoter, did exhibit synergy. PDX-1 was shown further to activate the endogenous insulin 1 gene in alphaTC1.6 cells, whereas MafA activated the insulin 2 gene. In combination, PDX-1 and MafA activated both insulin genes. Chromatin immunoprecipitation assays confirmed that PDX-1 increased the association of acetylated histones H3 and H4 with the insulin 1 gene and MafA increased the association of acetylated histone H3 with the insulin 2 gene.

A simple cosmology with a varying fine structure constant.

We investigate the cosmological consequences of a theory in which the electric charge e can vary. In this theory the fine structure "constant," alpha, remains almost constant in the radiation era, undergoes a small increase in the matter era, but approaches a constant value when the universe starts accelerating because of a positive cosmological constant. This model satisfies geonuclear, nucleosynthesis, and cosmic microwave background constraints on time variation in alpha, while fitting the observed accelerating Universe and evidence for small alpha variations in quasar spectra. It also places specific restrictions on the nature of the dark matter. Further tests, involving stellar spectra and Eötvös experiments, are proposed.