Hyaluronic acid alters vessel behavior in CXCL12-treated HUVECs

Hyaluronic acid (HA) is a key component of the extracellular matrix known for absorbing water, swelling, and altering solid stress of tumors. HA’s anionic behavior may provide important biochemical effects toward tumor progression as well. Tumors obtain nutrients by relying on signaling molecules such as CXCL12 to recruit blood vessels and promote vessel leakage. Recent work suggests that additional positively-charged residues on CXCL12’s β and γ isoforms cause different biochemical functionality compared to the well-studied α isoform. These studies aimed to determine whether the presence of HA in a tumor’s microenvironment could alter the relative response strength of CXCL12’s various isoforms on blood vessel sprouting and apparent vascular permeability. The vessel microenvironment was modeled using a 3-channel microfluidic device with Human Umbilical Vein Endothelial Cells (HUVECs) in the outer channels forming monolayers against a 3D collagen or collagen/HA matrix in the center channel. HUVECs were cultured with media containing recombinant CXCL12 (α, β or γ). Results show that total HUVEC sprouting area follows an α>β>γ trend in isoform-treated HUVECs within a collagen matrix, matching the binding affinity order of CXCL12 to endothelial CXCR4 receptors. The presence of HA decreased overall sprouting response but shifted pro-angiogenic potency towards CXCL12’s γ isoform. Vascular permeability studies also showed an α>β>γ trend for HUVECs in collagen. With HA added, control and α-treated HUVECs became less permeable while γ-treated HUVECs became more permeable. Overall results suggest that an HA-infused collagen matrix facilitates γ isoform binding, leading to a stronger isoform-specific vessel response. Knowing how HA impacts CXCL12 isoform potency on vessels will help in the future design of CXCL12-targeted cancer therapies.The American Heart AssociationInstitute for Materials Research at OSULumley Engineering FundPelotoniaA one-year embargo was granted for this item.Academic Major: Chemical Engineerin

Chronic Progressive External Ophthalmoplegia Is Associated with a Novel Mutation in the Mitochondrial tRNA(Asn) Gene

Chronic progressive external ophthalmoplegia (CPEO) is caused by a decreased oxidative phosphorylation (OXPHOS) activity due to large-scale deletions of the mitochondrial genome in 50 % of the patients. The deletions encompass structural OXPHOS genes as well as tRNA genes, required for their expression so that the pathogenesis could be due to the deleted OXPHOS subunits or to an impaired mitochondrial translation. We have analyzed the mitochondrial genome of a patient presenting with CPEO for single base substitutions and discovered a novel heteroplasmic mutation in the tRNAAsn gene at position 5692 that converts a highly conserved adenine into a guanine. This mutation is unique because it is located at the transition of the anticodon loop to the anticodon stem and it leads to an additional base pair, thus reducing the number of loop-forming nucleotides from seven to five. Our findings suggest that CPEO can be caused by a single base substition in a mitochondrial tRNA gene so that the mitochondrial protein synthesis becomes the rate limiting step in OXPHOS fidelity

Effects of a multi-component exercise program and calcium–vitamin-D3-fortified milk on bone mineral density in older men : a randomised controlled trial

Summary We examined the independent and combined effects of a multi-component exercise program and calcium&ndash;vitamin-D3-fortified milk on bone mineral density (BMD) in older men. Exercise resulted in a 1.8% net gain in femoral neck BMD, but additional calcium&ndash;vitamin D3 did not enhance the response in this group of older well-nourished men.Introduction This 12-month randomised controlled trial assessed whether calcium&ndash;vitamin-D3-fortified milk could enhance the effects of a multi-component exercise program on BMD in older men.Methods Men (n&thinsp; =&thinsp;180) aged 50&ndash;79 years were randomised into: (1) exercise + fortified milk; (2) exercise; (3) fortified milk; or (4) controls. Exercise consisted of high intensity progressive resistance training with weight-bearing impact exercise. Men assigned to fortified milk consumed 400 mL/day of low fat milk providing an additional 1,000 mg/day calcium and 800 IU/day vitamin D3. Femoral neck (FN), total hip, lumbar spine and trochanter BMD and body composition (DXA), muscle strength 25-hydroxyvitamin D and parathyroid hormone (PTH) were assessed.Results There were no exercise-by-fortified milk interactions at any skeletal site. Exercise resulted in a 1.8% net gain in FN BMD relative to no-exercise (p&thinsp;&lt;&thinsp;0.001); lean mass (0.6 kg, p&thinsp;&lt;&thinsp;0.05) and muscle strength (20&ndash;52%, p&thinsp;&lt;&thinsp;0.001) also increased in response to exercise. For lumbar spine BMD, there was a net 1.4&ndash;1.5% increase in all treatment groups relative to controls (all p&thinsp;&lt;&thinsp;0.01). There were no main effects of fortified milk at any skeletal site.Conclusion A multi-component community-based exercise program was effective for increasing FN BMD in older men, but additional calcium&ndash;vitamin D3 did not enhance the osteogenic response.<br /

Potential ring of Dirac nodes in a new polymorph of Ca3_3P2_2

We report the crystal structure of a new polymorph of Ca$_3$P$_2$, and an analysis of its electronic structure. The crystal structure was determined through Rietveld refinements of powder synchrotron x-ray diffraction data. Ca$_3$P$_2$ is found to be a variant of the Mn$_5$Si$_3$ structure type, with a Ca ion deficiency compared to the ideal 5:3 stoichiometry to yield a charge-balanced compound. We also report the observation of a secondary phase, Ca$_5$P$_3$H, in which the Ca and P sites are fully occupied and the presence of interstitial hydride ions creates a closed-shell electron-precise compound. We show via electronic structure calculations of Ca$_3$P$_2$ that the compound is stabilized by a gap in the density of states compared to the hypothetical compound Ca$_5$P$_3$. Moreover, the calculated band structure of Ca$_3$P$_2$ indicates that it should be a three-dimensional Dirac semimetal with a highly unusual ring of Dirac nodes at the Fermi level. The Dirac states are protected against gap opening by a mirror plane in a manner analogous to graphene. The results suggest that further study of the electronic properties of Ca$_3$P$_2$ will be of interest

Flight of the Vampire: Ontogenetic Gait-Transition in \u3cem\u3eVampyroteuthis Infernalis\u3c/em\u3e (Cephalopoda: Vampyromorpha)

Vampyroteuthis infernalis is a cosmopolitan cephalopod that lives in the oxygen minimum layer between 600 and 800 m depth. Morphometric and physiological studies have indicated that V. infernalis has little capacity for jet propulsion and has the lowest metabolic rate ever measured for a cephalopod. Because fin swimming is inherently more efficient than jet propulsion, some of the reduction in energy usage relative to other cephalopods may result from the use of fins as the primary means of propulsion. V. infernalis undergoes a rapid metamorphosis which consists of changes in the position, size and shape of the fins. This suggests that there are changes in the selective factors affecting locomotion through ontogeny. The present study describes these changes in relation to models for underwater ‘flight’. Citrate synthase (CS) and octopine dehydrogenase (ODH) activities, indicative of aerobic and anaerobic metabolism, respectively, were measured in fin, mantle and arm tissue across a range of body size of four orders of magnitude. The low enzymatic activities in both posterior and anterior fin tissue and the relatively high activity in mantle muscle prior to metamorphosis indicate that jet propulsion using mantle contraction is the primary means of propulsion in juvenile V. infernalis. The increase in CS activity with size after metamorphosis suggests an increased use of the fins for lift-based propulsion. Fin swimming appears to be the primary means of propulsion at all adult sizes. The negative allometry of CS activity in mantle and arm muscle is consistent with the scaling of oxygen consumption previously measured for V. infernalis and with the scaling of aerobic metabolism observed in most animals. The unusual positive allometry of fin muscle CS activity suggests that the use of fins is either relatively more important or more costly in larger animals. Positive scaling of ODH activity in all tissues suggests that fin propulsion, jet propulsion and medusoid ‘bell-swimming’ are all important for burst escape responses. Enzyme activities in Cirrothauma murrayi are consistent with finswimming observed from submersibles, while those in Opisthoteuthis californiana suggest a strong reliance on medusoid swimming using the arms. The transition from jet propulsion to paired-fin ‘flight’ with increasing body size in Vampyroteuthis infernalis appears functionally to be an ontogenetic ‘gait-transition’