The material properties of naked mole-rat hyaluronan.

Hyaluronan (HA) is a key component of the extracellular matrix. Given the fundamental role of HA in the cancer resistance of the naked mole-rat (NMR), we undertook to explore the structural and soft matter properties of this species-specific variant, a necessary step for its development as a biomaterial. We examined HA extracted from NMR brain, lung, and skin, as well as that isolated from the medium of immortalised cells. In common with mouse HA, NMR HA forms a range of assemblies corresponding to a wide distribution of molecular weights. However, unique to the NMR, are highly folded structures, whose characteristic morphology is dependent on the tissue type. Skin HA forms tightly packed assemblies that have spring-like mechanical properties in addition to a strong affinity for water. Brain HA forms three dimensional folded structures similar to the macroscopic appearance of the gyri and sulci of the human brain. Lung HA forms an impenetrable mesh of interwoven folds in a morphology that can only be described as resembling a snowman. Unlike HA that is commercially available, NMR HA readily forms robust gels without the need for chemical cross-linking. NMR HA gels sharply transition from viscoelastic to elastic like properties upon dehydration or repeated loading. In addition, NMR HA can form ordered thin films with an underlying semi-crystalline structure. Given the role of HA in maintaining hydration in the skin it is plausible that the folded structures contribute to both the elasticity and youthfulness of NMR skin. It is also possible that such densely folded materials could present a considerable barrier to cell invasion throughout the tissues, a useful characteristic for a biomaterial.This work was supported by a Cancer Research UK/RCUK Multidisciplinary Project Award (C56829/A22053) to K.R., E.S. and D.F. and a Cancer Research UK Career Establishment Award (C47525/A17348) to W.T.K. F.H. and S.C. were supported by Gates Cambridge Trust scholarships

Genome-wide association analysis identifies six new loci associated with forced vital capacity

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease

Elevating the ‘open’ Conversation: Access to Health Information as a Social Justice Concern

Social justice, including equitable access to information and bridging the digital divide, are concepts familiar to many librarians. As a result, these ideas create a natural intersection for advocacy as health information professionals. As a brief background before the panel, we will review the literature on open access and social justice to provide context for the topic, and discuss survey results from undergraduate student opinions regarding open access. Panelists will then speak to the topic from their individual perspectives, and the audience will have an opportunity to engage and ask questions

Isolation from oil reservoirs of novel thermophilic anaerobes phylogenetically related to Thermoanaerobacter subterraneus: reassignment of T. subterraneus, Thermoanaerobacter yonseiensis, Thermoanaerobacter tengcongensis and Carboxydibrachium pacificum to Caldanaerobacter subterraneus gen. nov., sp. nov., comb. nov. as four novel subspecies

Novel thermophilic, anaerobic, Gram-positive, rod-shaped bacteria, strains SL9 and OCA1, were isolated from oilfields in France and Australia, respectively. Both strains, together with Thermoanaerobacter yonseiensis KB-1T (=DSM 13777T), Thermoanaerobacter tengcongensis MB4T (=DSM 15242T) and Carboxydibrachium pacificum JMT (=DSM 12653T), possessed genomic (DNA–DNA hybridization studies) and phylogenetic similarities with Thermoanaerobacter subterraneus SEBR 7858T (=DSM 13054T), which was isolated recently from an oilfield reservoir in south-west France. Marked phenotypic differences exist between the three oilfield isolates (T. subterraneus, strain OCA1 and strain SL9): they include temperature range for growth and substrates used. Differences were also observed in the DNA G+C contents of all organisms. Similarly to T. subterraneus, strains SL9 and OCA1, and also T. yonseiensis, T. tengcongensis and Carboxydibrachium pacificum, produced acetate and L-alanine as major end products of glucose metabolism [0·8–1·0 mol L-alanine produced (mol glucose consumed)−1] and reduced thiosulfate, but not sulfate, to sulfide. Because of these significant metabolic and phylogenetic differences between the oilfield isolates (T. subterraneus, strain OCA1 and strain SL9), T. yonseiensis, T. tengcongensis and Carboxydibrachium pacificum and other Thermoanaerobacter species, it is proposed to reassign them as a novel genus and species, Caldanaerobacter subterraneus gen. nov., sp. nov., comb. nov., with the creation of four novel subspecies, Caldanaerobacter subterraneus subsp. subterraneus subsp. nov., comb. nov., Caldanaerobacter subterraneus subsp. yonseiensis subsp. nov., comb. nov., Caldanaerobacter subterraneus subsp. tengcongensis subsp. nov., comb. nov. and Caldanaerobacter subterraneus subsp. pacificus subsp. nov., comb. nov

Cholesterol-rich naked mole-rat brain lipid membranes are susceptible to amyloid beta-induced damage in vitro.

Naked mole-rats are extraordinarily long-lived rodents that offer unique opportunities to study the molecular origins of age-related neurodegenerative diseases. Remarkably, they do not accumulate amyloid plaques, even though their brains contain high concentrations of amyloid beta (Aβ) peptide from a young age. Therefore, they represent a particularly favourable organism to study the mechanisms of resistance against Aβ neurotoxicity. Here we examine the composition, phase behaviour, and Aβ interactions of naked mole-rat brain lipids. Relative to mouse, naked mole-rat brain lipids are rich in cholesterol and contain sphingomyelin in lower amounts and of shorter chain lengths. Proteins associated with the metabolism of ceramides, sphingomyelins and sphingosine-1-phosphate receptor 1 were also found to be decreased in naked mole-rat brain lysates. Correspondingly, we find that naked mole-rat brain lipid membranes exhibit a high degree of phase separation, with the liquid ordered phase extending to 80% of the supported lipid bilayer. These observations are consistent with the 'membrane pacemaker' hypothesis of ageing, according to which long-living species have lipid membranes particularly resistant to oxidative damage. We also found that exposure to Aβ disrupts naked mole-rat brain lipid membranes significantly, breaking the membrane into pieces while mouse brain derived lipids remain largely intact upon Aβ exposure

Lipid membranes from naked mole-rat brain lipids are cholesterol-rich, highly phase-separated, and sensitive to amyloid-induced damage

Naked mole-rats are extraordinarily long-lived rodents that do not develop age-relatedneurodegenerative diseases. Remarkably, they do not accumulate amyloid plaques, even though theirbrains contain high concentrations of amyloid beta peptide, even from a young age Therefore, theseanimals offer an opportunity to investigate mechanisms of resistance against the neurotoxicity ofamyloid beta aggregation. Working in this direction, here we examine the composition, phasebehaviour, and amyloid beta interactions of naked mole-rat brain lipids. Relative to mouse, nakedmole-rat brain lipids are rich in cholesterol and contain sphingomyelin in lower amounts and of shorterchain lengths. Proteins associated with metabolism of ceramides, sphingomyelin and ceramidereceptor activity were also found to be decreased in naked mole-rat brain lysates. Correspondingly,we find that naked mole-rat brain lipid membranes exhibit a high degree of phase separation, withthe liquid ordered phase occupying up to 80% of the supported lipid bilayer. These observations areconsistent with the ‘membrane pacemaker’ hypothesis of ageing, according to which long-livingspecies have lipid membranes particularly resistant to oxidative damage. However, we found thatexposure to amyloid beta disrupts the naked mole-rat brain lipid membranes while those formed frommouse brain lipids exhibit small, well-defined footprints, whereby the amyloid beta penetrates deeplyinto the lipid membranes. These results suggest that in naked mole-rats the lipid composition of cellmembranes may offer neuroprotection through resistance to oxidative processes rather than throughmechanical effects