Influence of GABA and GABA-producing Lactobacillus brevis DPC 6108 on the development of diabetes in a streptozotocin rat model

peer-reviewedThe aim of this study was to investigate if dietary administration of γ-aminobutyric acid (GABA)-producing Lactobacillus brevis DPC 6108 and pure GABA exert protective effects against the development of diabetes in streptozotocin (STZ)-induced diabetic Sprague Dawley rats. In a first experiment, healthy rats were divided in 3 groups (n=10/group) receiving placebo, 2.6 mg/kg body weight (bw) pure GABA or L. brevis DPC 6108 (~109microorganisms). In a second experiment, rats (n=15/group) were randomised to five groups and four of these received an injection of STZ to induce type 1 diabetes. Diabetic and non-diabetic controls received placebo [4% (w/v) yeast extract in dH2O], while the other three diabetic groups received one of the following dietary supplements: 2.6 mg/kg bw GABA (low GABA), 200 mg/kg bw GABA (high GABA) or ~109 L. brevis DPC 6108. L. brevis DPC 6108 supplementation was associated with increased serum insulin levels (P0.05), compared with non-diabetic controls while all other diabetic groups displayed reduced diversity (P<0.05). L. brevis DPC 6108 attenuated hyperglycaemia induced by diabetes but additional studies are needed to understand the mechanisms involved in this reduction.The authors and their work were supported by the APC Microbiome Institute. The APC Microbiome Institute is funded by Science Foundation Ireland (SFI). This publication has emanated from research supported by a research grant from Science Foundation Ireland (SFI) under Grant Number SFI/12/RC/2273

Bifidobacterium breve with a-linolenic acid alters the composition, distribution and transcription factor activity associated with metabolism and absorption of fat

This study focused on the mechanisms that fatty acid conjugating strains - Bifidobacterium breve NCIMB 702258 and Bifidobacterium breve DPC 6330 - influence lipid metabolism when ingested with α-linolenic acid (ALA) enriched diet. Four groups of BALB/c mice received ALA enriched diet (3% (w/w)) either alone or in combination with B. breve NCIMB 702258 or B. breve DPC 6330 (109 CFU/day) or unsupplemented control diet for six weeks. The overall n-3 PUFA score was increased in all groups receiving the ALA enriched diet. Hepatic peroxisomal beta oxidation increased following supplementation of the ALA enriched diet with B. breve (P < 0.05) and so the ability of the strains to produce c9t11 conjugated linoleic acid (CLA) was identified in adipose tissue. Furthermore, a strain specific effect of B. breve NCIMB 702258 was found on the endocannabinoid system (ECS). Liver triglycerides (TAG) were reduced following ALA supplementation, compared with unsupplemented controls (P < 0.01) while intervention with B. breve further reduced liver TAG (P < 0.01), compared with the ALA enriched control. These data indicate that the interactions of the gut microbiota with fatty acid metabolism directly affect host health by modulating n-3 PUFA score and the ECS

A cryogenic beam of refractory, chemically reactive molecules with expansion cooling

Cryogenically cooled buffer gas beam sources of the molecule thorium monoxide (ThO) are optimized and characterized. Both helium and neon buffer gas sources are shown to produce ThO beams with high flux, low divergence, low forward velocity, and cold internal temperature for a variety of stagnation densities and nozzle diameters. The beam operates with a buffer gas stagnation density of ~10^15-10^16 cm^-3 (Reynolds number ~1-100), resulting in expansion cooling of the internal temperature of the ThO to as low as 2 K. For the neon (helium) based source, this represents cooling by a factor of about 10 (2) from the initial nozzle temperature of about 20 K (4 K). These sources deliver ~10^11 ThO molecules in a single quantum state within a 1-3 ms long pulse at 10 Hz repetition rate. Under conditions optimized for a future precision spectroscopy application [A C Vutha et al 2010 J. Phys. B: At. Mol. Opt. Phys. 43 074007], the neon-based beam has the following characteristics: forward velocity of 170 m/s, internal temperature of 3.4 K, and brightness of 3x10^11 ground state molecules per steradian per pulse. Compared to typical supersonic sources, the relatively low stagnation density of this source, and the fact that the cooling mechanism relies only on collisions with an inert buffer gas, make it widely applicable to many atomic and molecular species, including those which are chemically reactive, such as ThO

“We Used to Say Rats Fell from the Sky After a Flood:” Temporary Recovery of Muskrat Following Ice Jams in the Peace-Athabasca Delta

Elders and Indigenous land users in the Peace-Athabasca Delta (PAD) have observed a dramatic decline in the relative abundance of muskrat in recent decades (~1935–2014). The main explanation for the decline has been reduction in suitable habitat as a result of decades with reduced frequency of ice-jam flooding on the Peace River. Under favourable conditions, ice jams can cause flooding of perched basins within the PAD that would otherwise receive no recharge from floodwaters. To examine whether abundance of muskrat in the PAD is driven by flooding, we tested the predictions that the density of muskrat (estimated by winter counts of houses) (1) was inversely related to the number of years since major ice jam floods and (2) increased with water depth. An ongoing collaborative monitoring program initiated in 2011, combined with analysis of data from past surveys (1973–2015), allowed Indigenous land users and scientists to document a 10 to 100-fold increase in the density of muskrat houses in 24 basins, over the two years following ice-jam flood events in the PAD. During 1973–2015, in the periods between major floods, density of houses dropped by approximately 79% for every year after a significant flood. In 27 basins surveyed from 2011 to 2015, density of muskrat houses increased by two orders of magnitude in the two years following a flood in the spring of 2014. Density of muskrat houses had a non-linear relationship with estimated depth of water at the time of fall freeze-up; the highest densities of muskrat houses were in basins with about 60 – 250 cm of water at the time of freeze-up. The depth of snow at the time of surveys did not have a strong relationship with the density of muskrat houses. However, few houses were counted in basins with more than 20 cm of snow, likely because deeper snow made it more difficult to conduct surveys and spot houses. Factors other than an increase in the depth of water at fall freeze-up may provide the mechanisms by which flooding affects muskrat. Density of muskrat houses is clearly tied to ice-jam flooding in the PAD. However, the local mechanisms by which floods affect muskrat are best understood by Indigenous land users and remain poorly understood by Western science. Indigenous peoples continue to regard muskrat as an indicator of ecological and cultural health of the PAD. This study highlights the value of consistent ecological monitoring that includes Indigenous knowledge.Les aînés et les utilisateurs des terres autochtones du delta des rivières de la Paix et Athabasca ont observé une baisse draconienne de l’abondance du rat musqué au cours des dernières décennies (~1935-2014). La principale explication du déclin est la diminution d’abris convenables, et ce, en raison de plusieurs décennies marquées par la fréquence réduite d’inondations causées par des embâcles dans la rivière de la Paix. Dans des conditions favorables, les embâcles peuvent causer l’inondation des bassins perchés au sein du delta des rivières de la Paix et Athabasca qui autrement ne recevraient pas de recharge des eaux de crue. Afin d’examiner si l’abondance du rat musqué dans le delta des rivières de la Paix et Athabasca est favorisée par les inondations, nous avons testé des prévisions selon lesquelles la densité du rat musqué (estimée par le nombre d’abris en hiver) 1) était inversement liée au nombre d’années depuis les dernières importantes inondations causées par des embâcles et 2) augmentait avec la profondeur de l’eau. Un programme collaboratif de suivi continu lancé en 2011, combiné à l’analyse de données des relevés antérieurs (1973-2015), a permis aux utilisateurs des terres autochtones et aux scientifiques de multiplier de 10 à 100 fois la densité d’abris du rat musqué dans 24 bassins, au cours des deux années suivant des événementsd’inondation causés par des embâcles dans le delta des rivières de la Paix et Athabasca. Entre 1973 et 2015, durant les périodes se situant entre les inondations importantes, la densité d’abris a diminué d’environ 79 % chaque année suivant une inondation importante. Dans 27 bassins sondés entre 2011 et 2015, la densité d’abris du rat musqué a augmenté de deux ordres de grandeur au cours des deux années ayant suivi une inondation survenue au printemps de 2014. La densité d’abris du rat musqué avait une relation non linéaire avec la profondeur de l’eau estimée au moment de la prise des glaces en automne; les plus fortes densités d’abris du rat musqué se trouvaient dans les bassins ayant de 60 à 250 cm d’eau au moment de la prise des glaces. La profondeur de la neige au moment des relevés n’avait pas de relation solide avec la densité d’abris du rat musqué. Cependant, nous avons compté peu d’abris dans les bassins comptant plus de 20 cm de neige, probablement parce qu’il était plus difficile d’effectuer des relevés et de trouver les abris dans la neige plus épaisse. Des facteurs autres que l’augmentation de la profondeur de l’eau au moment de la prise des glaces en automne pourraient fournir les mécanismes par lesquels les inondations se répercutent sur les rats musqués. La densité d’abris du rat musqué est manifestement liée aux inondations causées par des embâcles dans le delta des rivières de la Paix et Athabasca. Toutefois, les utilisateurs des terres autochtones comprennent mieux les mécanismes locaux par lesquels les inondations se répercutent sur les rats musqués, tandis qu’ils demeurent mal compris par la science occidentale. Les peuples autochtones continuent de considérer le rat musqué comme un indicateur de la santé écologique et culturelle du delta des rivières de la Paix et Athabasca. Cette étude fait ressortir la valeur d’un suivi écologique constant qui tient compte des connaissances autochtones

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

The Pochonia chlamydosporia Serine Protease Gene vcp1 Is Subject to Regulation by Carbon, Nitrogen and pH: Implications for Nematode Biocontrol

The alkaline serine protease VCP1 of the fungus Pochonia chlamydosporia belongs to a family of subtilisin-like enzymes that are involved in infection of nematode and insect hosts. It is involved early in the infection process, removing the outer proteinaceous vitelline membrane of nematode eggs. Little is known about the regulation of this gene, even though an understanding of how nutrients and other factors affect its expression is critical for ensuring its efficacy as a biocontrol agent. This paper provides new information on the regulation of vcp1 expression. Sequence analysis of the upstream regulatory region of this gene in 30 isolates revealed that it was highly conserved and contained sequence motifs characteristic of genes that are subject to carbon, nitrogen and pH-regulation. Expression studies, monitoring enzyme activity and mRNA, confirmed that these factors affect VCP1 production. As expected, glucose reduced VCP1 expression and for a few hours so did ammonium chloride. Surprisingly, however, by 24 h VCP1 levels were increased in the presence of ammonium chloride for most isolates. Ambient pH also regulated VCP1 expression, with most isolates producing more VCP1 under alkaline conditions. There were some differences in the response of one isolate with a distinctive upstream sequence including a variant regulatory-motif profile. Cryo-scanning electron microscopy studies indicated that the presence of nematode eggs stimulates VCP1 production by P. chlamydosporia, but only where the two are in close contact. Overall, the results indicate that readily-metabolisable carbon sources and unfavourable pH in the rhizosphere/egg-mass environment may compromise nematode parasitism by P. chlamydosporia. However, contrary to previous indications using other nematophagous and entomopathogenic fungi, ammonium nitrate (e.g. from fertilizers) may enhance biocontrol potential in some circumstances