Lin28A induces energetic switching to glycolytic metabolism in human embryonic kidney cells

Background: Loss of a cell’s capacity to generate sufficient energy for cellular functions is a key hallmark of the ageing process and ultimately leads to a variety of important age-related pathologies such as cancer, Parkinson’s disease and atherosclerosis. Regenerative medicine has sought to reverse these pathologies by reprogramming somatic cells to a more juvenile energetic state using a variety of stem cell factors. One of these factors, Lin28, is considered a candidate for modification in the reprogramming of cellular energetics to ameliorate the ageing process while retaining cell phenotype. Results: Over-expression of Lin28A resulted in key changes to cellular metabolism not observed in wild-type controls. Extracellular pH flux analysis indicated that Lin28A over expression significantly increased the rate of glycolysis, whilst high resolution oxygen respirometry demonstrated a reduced oxygen consumption. Western blot and real-time PCR analysis identified Hexokinase II as one of the key modulators of glycolysis in these cells which was further confirmed by increased glucose transport. A metabolic switching effect was further emphasised by Western blot analysis where the oxygen consuming mitochondrial complex IV was significantly reduced after Lin28A over expression. Conclusions: Results from this study confirm that Lin28A expression promotes metabolic switching to a phenotype that relies predominantly on glycolysis as an energy source, while compromising oxidative phosphorylation. Mechanisms to augment regulated Lin28A in age related pathologies that are characterised by mitochondria dysfunction or in differentiated and aged post-mitotic cells is the future goal of this work

Direct administration of 2-hydroxypropyl-beta-cyclodextrin into guinea pig cochleae: Effects on physiological and histological measurements

<p>Cochlear response measurements from two different animals made before (red) and after (blue) treatment with HPβCD (Panel A) and TTX (Panel B) to 80 dB SPL 4 kHz tone bursts. Cochlear response waveform maintained CAP-like morphology after HPβCD treatment, consistent with reduced mechanical drive to neural excitation (Panel B, blue). In contrast, response waveform is EPSP-like following TTX treatment. Unlike TTX, results from HPβCD do not support the hypothesis that the auditory nerve is a site of action for 13 mM HPβCD.</p

Near-infrared light increases ATP, extends lifespan and improves mobility in aged Drosophila melanogaster.

Ageing is an irreversible cellular decline partly driven by failing mitochondrial integrity. Mitochondria accumulate DNA mutations and reduce ATP production necessary for cellular metabolism. This is associated with inflammation. Near-infrared exposure increases retinal ATP in old mice via cytochrome c oxidase absorption and reduces inflammation. Here, we expose fruitflies daily to 670 nm radiation, revealing elevated ATP and reduced inflammation with age. Critically, there was a significant increase in average lifespan: 100-175% more flies survived into old age following 670 nm exposure and these had significantly improved mobility. This may be a simple route to extending lifespan and improving function in old age

High-resolution genome-wide scan of genes, gene-networks and cellular systems impacting the yeast ionome

Peer reviewedPublisher PD

Losses in the Post-Collision Extraction Line

The CLIC beam delivery system focuses 1.5 TeV electron and positron beams to a nanometre-sized cross section when colliding them at the interaction point (IP). The intense focusing leads to large beam-beam effects, causing the production of beamstrahlung photons, coherent and incoherent e+e− pairs, as well as a significant disruption of the main beam. The transport of the post-collision beams requires a minimal loss extraction line, with high acceptance for energy deviation and divergence. The current design includes vertical bends close to the IP in order to separate the charged particles with a sign opposite to the main beam into a diagnostic-equipped intermediate dump, whilst transporting the photons and the main beam to the final dump. Photon and charged particle losses on magnet masks and dumps result in a complex radiation field and IP background particle fluxes. In this paper, the electromagnetic backgrounds at the IP arising from the losses occurring closest to the collision point are calculated

Photon backgrounds at the CLIC interaction point due to losses in the post-collision extraction line

The CLIC beam delivery system focuses 1.5~TeV electron and positron beams to a nanometre-sized cross section when colliding them at the interaction point (IP). The intense focusing leads to large beam-beam effects, causing the production of beamstrahlung photons, coherent and incoherent $e^+e^-$ pairs, as well as a significant disruption of the main beam. The transport of the post-collision beams requires a minimal loss extraction line, with high acceptance for energy deviation and divergence. The current design includes vertical bends close to the IP in order to separate the charged particles with a sign opposite to the main beam into a diagnostic-equipped intermediate dump, whilst transporting the photons and the main beam to the final dump. Photon and charged particle losses on magnet masks and dumps result in a complex radiation field and IP background particle fluxes. In this paper, the electromagnetic backgrounds at the IP arising from the losses occurring closest to the collision point are calculated

The evolution of gregariousness in parasitoid wasps

Data are assembled on the clutch-size strategies adopted by extant species of parasitoid wasp. These data are used to reconstruct the history of clutch-size evolution in the group using a series of plausible evolutionary assumptions. Extant families are either entirely solitary, both solitary and gregarious, or else clutch size is unknown. Parsimony analysis suggests that the ancestors of most families were solitary, a result which is robust to different phylogenetic relationships and likely data inadequacies. This implies that solitariness was ubiquitous throughout the initial radiation of the group, and that transitions to gregariousness have subsequently occurred a minimum of 43 times in several, but not all lineages. Current data suggest that species-rich and small-bodied lineages are more likely to have evolved gregariousness, and contain more species with small gregarious brood sizes. I discuss the implications of these data for clutch-size theory

Transcriptional plasticity buffers genetic variation in zinc homeostasis

In roots of Arabidopsis thaliana, Zn can be either loaded into the xylem for translocation to the shoot or stored in vacuoles. Vacuolar storage is achieved through the action of the Zn/Cd transporter HMA3 (Heavy Metal Atpase 3). The Col-0 accession has an HMA3 loss-of-function allele resulting in high shoot Cd, when compared to accession CSHL-5 which has a functional allele and low shoot Cd. Interestingly, both Col-0 and CSHL-5 have similar shoot Zn concentrations. We hypothesize that plants sense changes in cytosolic Zn that are due to variation in HMA3 function, and respond by altering expression of genes related to Zn uptake, transport and compartmentalisation, in order to maintain Zn homeostasis. The expression level of genes known to be involved in Zn homeostasis were quantified in both wild-type Col-0 and Col-0::HMA3CSHL-5 plants transformed with the functional CSHL-5 allele of HMA3. We observed significant positive correlations between expression of HMA3 and of genes known to be involved in Zn homeostasis, including ZIP3, ZIP4, MTP1, and bZIP19. The results support our hypothesis that alteration in the level of function of HMA3 is counterbalanced by the fine regulation of the Zn homeostasis gene network in roots of A. thaliana

Arabidopsis thaliana zinc accumulation in leaf trichomes is correlated with zinc concentration in leaves

Zinc (Zn) is a key micronutrient for plants and animals, and understanding Zn homeostasis in plants can improve both agriculture and human health. While root Zn transporters in plant model species have been characterized in detail, comparatively little is known about shoot processes controlling Zn concentrations and spatial distribution. Previous work showed that Zn hyperaccumulator species such as Arabidopsis halleri accumulate Zn and other metals in leaf trichomes. To date there is no systematic study regarding Zn accumulation in the trichomes of the non-accumulating, genetic model species A. thaliana. Here, we used Synchrotron X-Ray Fluorescence mapping to show that Zn accumulates at the base of trichomes of A. thaliana. Using transgenic and natural accessions of A thaliana that vary in bulk leaf Zn concentration, we demonstrate that higher leaf Zn increases total Zn found at the base of trichome cells. Our data indicates that Zn accumulation in trichomes is a function of the Zn status of the plant, and provides the basis for future studies on a genetically tractable plant species to understand the molecular steps involved in Zn spatial distribution in leaves

Effects of aspect ratio on the mode couplings of thin-film bulk acoustic wave resonators

We studied mode couplings in thin film bulk acoustic wave resonators of a piezoelectric film on a dielectric layer operating with the fundamental thickness-extensional mode. A system of plate equations derived in our previous paper was used which includes the couplings to the unwanted in-plane extension, flexure, fundamental and second-order thickness shear modes. It was shown that the couplings depend strongly on the plate length/thickness ratio. For a relatively clean operating mode with weak couplings to unwanted modes, a series of discrete values of the plate length/thickness ratio should be avoided and these values were determined in the present paper. The results can be of great significance to the design and optimization of film bulk acoustic wave resonators