Microbial Community Evolution Is Significantly Impacted by the Use of Calcium Isosaccharinic Acid as an Analogue for the Products of Alkaline Cellulose Degradation

Diasteriomeric isosaccharinic acid (ISA) is an important consideration within safety assessments for the disposal of the United Kingdoms’ nuclear waste legacy, where it may potentially influence radionuclide migration. Since the intrusion of micro-organisms may occur within a disposal concept, the impact of ISA may be impacted by microbial metabolism. Within the present study we have established two polymicrobial consortia derived from a hyperalkaline soil. Here, α-ISA and a diatereomeric mix of ISAs’ were used as a sole carbon source, reflecting two common substrates appearing within the literature. The metabolism of ISA within these two consortia was similar, where ISA degradation resulted in the acetogenesis and hydrogenotrophic methanogenesis. The chemical data obtained confirm that the diastereomeric nature of ISA is likely to have no impact on its metabolism within alkaline environments. High throughput sequencing of the original soil showed a diverse community which, in the presence of ISA allowed for the dominance the Clostridiales associated taxa with Clostridium clariflavum prevalent. Further taxonomic investigation at the genus level showed that there was in fact a significant difference (p = 0.004) between the two community profiles. Our study demonstrates that the selection of carbon substrate is likely to have a significant impact on microbial community composition estimations, which may have implications with respect to a safety assessment of an ILW-GDF

C, S, Zn and Cu abundances in planet-harbouring stars

We present a detailed and uniform study of C, S, Zn and Cu abundances in a large set of planet host stars, as well as in a homogeneous comparison sample of solar-type dwarfs with no known planetary-mass companions. Carbon abundances were derived by {EW} measurement of two C I optical lines, while spectral syntheses were performed for S, Zn and Cu. We investigated possible differences in the behaviours of the volatiles C, S and Zn and in the refractory Cu in targets with and without known planets in order to check possible anomalies due to the presence of planets. We found that the abundance distributions in stars with exoplanets are the high [Fe/H] extensions of the trends traced by the comparison sample. All volatile elements we studied show [X/Fe] trends decreasing with [Fe/H] in the metallicity range -0.8<[Fe/H]<0.5, with significantly negative slopes of -0.39+-0.04 and -0.35+-0.04 for C and S, respectively. A comparison of our abundances with those available in the literature shows good agreement in most cases.Comment: 28 pages, 13 figures, accepted for publication in A&

Induction maintenance concept for HAART as initial treatment in HIV infected infants

<p>Abstract</p> <p>Background</p> <p>Early initiated antiretroviral therapy (ART) in HIV infected infants leads to improved long-term viral suppression and survival. Guidelines recommend initiating therapy with a triple ART consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) and either one additional non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). Compared to older children and adults, viral relapse is seen more frequently in infants receiving triple ART. We now address the possibility of a more potent ART with a quadruple induction and triple maintenance therapy.</p> <p>Methods</p> <p>We examine the longitudinal course in four HIV infected infants, who were referred from other centers and could not be recruited to multicentre trials. We introduced ART initially consisting of two NRTIs, one NNRTI and one PI and later discontinued the PI at the age of 12 months maintaining a triple regime consisting of two NRTIs and one NNRTI.</p> <p>Results</p> <p>Provided that therapy adherence was maintained we observed an effective sustained decline of viral load and significant CD4 cell reconstitution even after switching to a triple regime. No drug associated toxicity was seen.</p> <p>Conclusion</p> <p>We suggest that a four drug therapy might be a possible initial therapy option in HIV infected infants, at least in those with a high viral load, followed by a maintenance triple regime after 12 months of therapy.</p

Meta-analysis of cognitive behaviour therapy and selective serotonin reuptake inhibitors for the treatment of hypochondriasis: Implications for trial design

Background: Classification of hypochondriasis as an obsessive-compulsive and related disorder in the International Classification of Diseases 11th Revision (ICD-11) has generated new heuristics for treatment of this common, chronic and disabling disorder. Standard treatment involves cognitive behaviour therapy (CBT) or selective serotonin reuptake inhibitors (SSRIs), but no meta-analysis has so far considered hypochondriasis as a structured diagnosis or assessed the role of medication. A clearer understanding of the relative effectiveness of these interventions and identification of clinically relevant factors moderating the treatment response is needed for clinical guideline development. Methods: The current systematic review and meta-analysis of interventions for hypochondriasis was preregistered on PROSPERO (CRD42020185768) and follows PRISMA guidelines. We searched MEDLINE, PsycINFO, and Cochrane Library databases until July 2021 for randomized controlled trials (RCTs) of interventions for patients diagnosed with hypochondriasis (or historical diagnostic equivalents). We assessed aspects of study quality using: the CONSORT Checklist for evaluation of RCTs, the Cochrane Risk of Bias 2 tool, researcher allegiance and treatment fidelity. The primary outcome was improvement in hypochondriasis symptoms, comparing intervention and control groups at trial endpoint. Moderator variables were assessed using subgroup and meta-regression analyses. Results: Searches identified 13 randomised controlled trials (RCTs) (N = 1405); 12 included CBT (N = 1212) and three included SSRI (N = 193) arms as the experimental intervention. Random effects meta-analysis yielded a moderate-to-large effect size for CBT versus all controls (g = −0.70 [95% CI -0.99 to −0.41], k = 18, I2 = 81.1%). Funnel plot asymmetry indicated possible publication bias and two potentially missing trials, reducing the effect size (g = −0.60 [95% CI -0.88 to −0.32]). Subgroup analysis showed that choice of control significantly moderated effect size, with those in CBT vs. wait-list (g = −1.32 [95% CI -1.75 to −0.90], k = 7, I2 = 0%) being double those of CBT vs. psychological or pharmacological placebo controls (g = −0.58 [95% CI -0.95 to −0.22], k = 7, I2 = 82%). Analysis of studies directly comparing CBT and SSRIs found a numerical, but not statistical advantage for SSRIs (g = 0.21 [95% CI -0.46 to 0.87], k = 2, I2 = 58.34%) and a modest effect size emerged for SSRIs vs. pill placebo (g = −0.29 [95% CI -0.57 to −0.01], k = 3, I2 = 0%). Most studies (11/13) were rated as high on potential researcher allegiance bias in favour of CBT. Meta-regressions revealed that effect sizes were larger in younger participants, and smaller in better quality and more recent RCTs and those with greater CBT fidelity. Conclusion: CBT and SSRIs are effective in the acute treatment of hypochondriasis, with some indication that intervention at a younger age produces better outcomes for CBT. In the case of CBT, effect sizes appear to have been significantly inflated by the use of wait list controls, and researcher allegiance bias. We recommend that a definitive, adequately controlled trial, designed with respect to the methodological issues raised in this meta-analysis, is needed to determine the magnitude effects for CBT and SSRIs with confidence and the long-term effect of treatments, to inform mental health service provision for this overlooked patient group

Temporal variability in large grazer space use in an experimental landscape

Land use, climate change, and their interaction each have great potential to affect grazing systems. With anticipated more frequent and extensive future drought, a more complete understanding of the mechanisms that determine large grazer landscape-level distribution under varying climatic conditions is integral to ecosystem management. Using an experimental setting with contrasting fire treatments, we describe the inter-annual variability of the effect of landscape topography and disturbance from prescribed spring fire on large grazer space use in years of variable resource availability. Using GPS telemetry, we investigated space use of plains bison (Bison bison bison) as they moved among watersheds managed with variable experimental burn treatments (1-, 2-, 4-, and 20-year burn intervals) during a seven-year period spanning years of average-to-above average forage production and severe drought. At the landscape scale, bison more strongly favored high-elevation and recently burned watersheds with watersheds burned for the first time in 2 or 4 yr consistently showing higher use relative to annually burned watersheds. In particular, watersheds burned for the first time in 4 yr were avoided to lesser extent than other more frequently burned watersheds during the dormant season. This management type also maintained coupling between bison space use and post-fire regrowth across post-drought growing season months, whereas watersheds with more frequent fire-return intervals attracted bison in only the first month post-fire. Hence, fire frequency played a role in maintaining the coupling of grazer and post-fire regrowth, the fire–grazer interaction, in response to drought-induced reduction in fuel loads. Moreover, bison avoided upland habitat in poor forage production years, when forage regrowth is less likely to occur in upland than in lowland habitats. Such quantified responses of bison to landscape features can aid future conservation management efforts and planning to sustain fire–grazer interactions and resulting spatial heterogeneity in grassland ecosystems

Temporal variability in large grazer space use in an experimental landscape

Land use, climate change, and their interaction each have great potential to affect grazing systems. With anticipated more frequent and extensive future drought, a more complete understanding of the mechanisms that determine large grazer landscape-level distribution under varying climatic conditions is integral to ecosystem management. Using an experimental setting with contrasting fire treatments, we describe the inter-annual variability of the effect of landscape topography and disturbance from prescribed spring fire on large grazer space use in years of variable resource availability. Using GPS telemetry, we investigated space use of plains bison (Bison bison bison) as they moved among watersheds managed with variable experimental burn treatments (1-, 2-, 4-, and 20-year burn intervals) during a seven-year period spanning years of average-to-above average forage production and severe drought. At the landscape scale, bison more strongly favored high-elevation and recently burned watersheds with watersheds burned for the first time in 2 or 4 yr consistently showing higher use relative to annually burned watersheds. In particular, watersheds burned for the first time in 4 yr were avoided to lesser extent than other more frequently burned watersheds during the dormant season. This management type also maintained coupling between bison space use and post-fire regrowth across post-drought growing season months, whereas watersheds with more frequent fire-return intervals attracted bison in only the first month post-fire. Hence, fire frequency played a role in maintaining the coupling of grazer and post-fire regrowth, the fire–grazer interaction, in response to drought-induced reduction in fuel loads. Moreover, bison avoided upland habitat in poor forage production years, when forage regrowth is less likely to occur in upland than in lowland habitats. Such quantified responses of bison to landscape features can aid future conservation management efforts and planning to sustain fire–grazer interactions and resulting spatial heterogeneity in grassland ecosystems

The impact of biofilms upon surfaces relevant to an intermediate level radioactive waste geological disposal facility under simulated near field conditions.

The ability of biofilms to form on a range of materials (cementious backfill (Nirex Reference Vault Backfill (NRVB)), graphite and stainless steel) relevant to potential UK intermediate level radioactive waste (ILW) disposal concepts was investigated by exposing these surfaces to alkaliphilic flocs generated by mature biofilm communities. Flocs are aggregates of biofilm material that are able to act as a transport vector for the propagation of biofilms.. In systems where biofilm formation was observed there was also a decrease in the sorption of isosaccharinic acids to the NRVB. The biofilms were composed of cells, extracellular DNA (eDNA), proteins and lipids with a smaller polysaccharide fraction, which was biased towards mannopyranosyl linked carbohydrates. The same trend was seen with the graphite and stainless steel surfaces at these pH values, but in this case the biofilms associated with the stainless steel surfaces had a distinct eDNA basal layer that anchored the biofilm to the surface. At pH 13 no structured biofilm was observed, rather all the surfaces accumulated an indistinct organic layer composed of biofilm materials. This was particularly the case for the stainless steel coupons which accumulated relatively large quantities of eDNA. The results demonstrate that there is the potential for biofilm formation in an ILW-GDF provided an initiation source for the microbial biofilm is present. They also suggest that even when conditions are too harsh for biofilm formation, exposed surfaces may accumulate organic material such as eDNA

A novel rhamnose-rich hetero-exopolysaccharide isolated from Lactobacillus paracasei DG activates THP-1 human monocytic cells

Lactobacillus paracasei DG is a bacterial strain with recognized probiotic properties and is used in commercial probiotic products. However, the mechanisms underlying its probiotic properties are mainly unknown. In this study, we tested the hypothesis that the capability of strain DG to interact with the host is, at least partly, associated with its ability to synthesize a surface-associated exopolysaccharide (EPS). Comparative genomics revealed the presence of putative EPS gene clusters in DG genome; accordingly, EPS was isolated from the surface of the bacterium. A sample of the pure EPS from strain DG (DG-EPS), upon NMR and chemical analyses, was shown to be a novel branched hetero-EPS with a repeat unit composed of L-rhamnose, D-galactose, and N-acetyl-D-galactosamine in a ratio of 4:1:1. Subsequently, we demonstrated that the DG-EPS displays immunostimulating properties by enhancing the gene expression of the pro-inflammatory cytokines TNF-α and IL-6, and, particularly, the chemokines IL-8 and CCL20 in the THP-1 human monocytic cell line. In contrast, the expression of the cyclooxygenase enzyme COX-2 was not affected. In conclusion, the DG-EPS is a bacterial macromolecule with the potential ability to boost the immune system as either a secreted molecule released from the bacterium or as a capsular envelope on the bacterial cell wall. This study provides additional information about the mechanisms supporting the cross-talk between L. paracasei DG and the host