Evidence for a Putative Isoprene Reductase in Acetobacterium wieringae

Recent discoveries of isoprene-metabolizing microorganisms suggest they might play an important role in the global isoprene budget. Under anoxic conditions, isoprene can be used as an electron acceptor and is reduced to methylbutene. This study describes the proteogenomic profiling of an isoprene-reducing bacterial culture to identify organisms and genes responsible for the isoprene hydrogenation reaction. A metagenome-assembled genome (MAG) of the most abundant (89% relative abundance) lineage in the enrichment, Acetobacterium wieringae, was obtained. Comparative proteogenomics and reverse transcription-PCR (RT-PCR) identified a putative five-gene operon from the A. wieringae MAG upregulated during isoprene reduction. The operon encodes a putative oxidoreductase, three pleiotropic nickel chaperones (2 × HypA, HypB), and one 4Fe-4S ferredoxin. The oxidoreductase is proposed as the putative isoprene reductase with a binding site for NADH, flavin adenine dinucleotide (FAD), two pairs of canonical [4Fe-4S] clusters, and a putative iron-sulfur cluster site in a Cys6bonding environment. Well-studied Acetobacterium strains, such as A. woodii DSM 1030, A. wieringae DSM 1911, or A. malicum DSM 4132, do not encode the isoprene-regulated operon but encode, like many other bacteria, a homolog of the putative isoprene reductase (;47 to 49% amino acid sequence identity). Uncharacterized homologs of the putative isoprene reductase are observed across the Firmicutes, Spirochaetes, Tenericutes, Actinobacteria, Chloroflexi, Bacteroidetes, and Proteobacteria, suggesting the ability of biohydrogenation of unfunctionalized conjugated doubled bonds in other unsaturated hydrocarbons

Hyporheic Zone Microbiome Assembly Is Linked to Dynamic Water Mixing Patterns in Snowmelt-Dominated Headwater Catchments

Terrestrial and aquatic elemental cycles are tightly linked in upland fluvial networks. Biotic and abiotic mineral weathering, microbially mediated degradation of organic matter, and anthropogenic influences all result in the movement of solutes (e.g., carbon, metals, and nutrients) through these catchments, with implications for downstream water quality. Within the river channel, the region of hyporheic mixing represents a hot spot of microbial activity, exerting significant control over solute cycling. To investigate how snowmelt-driven seasonal changes in river discharge affect microbial community assembly and carbon biogeochemistry, depth-resolved pore water samples were recovered from multiple locations around a representative meander on the East River near Crested Butte, CO, USA. Vertical temperature sensor arrays were also installed in the streambed to enable seepage flux estimates. Snowmelt-driven high river discharge led to an expanding zone of vertical hyporheic mixing and introduced dissolved oxygen into the streambed that stimulated aerobic microbial respiration. These physicochemical processes contributed to microbial communities undergoing homogenizing selection, in contrast to other ecosystems where lower permeability may limit the extent of mixing. Conversely, lower river discharge conditions led to a greater influence of upwelling groundwater within the streambed and a decrease in microbial respiration rates. Associated with these processes, microbial communities throughout the streambed exhibited increasing dissimilarity between each other, suggesting that the earlier onset of snowmelt and longer periods of base flow may lead to changes in the composition (and associated function) of streambed microbiomes, with consequent implications for the processing and export of solutes from upland catchments

Proteomics, a systems biology based approach to investigations of Jatropha curcas seeds

Poster presentation from IUFRO Tree Biotechnology Conference 2011: From Genomes to Integration and Delivery Arraial dAjuda, Bahia, Brazil. 26 June - 2 July 2011(VLID)90651

OX40 and 4-1BB delineate distinct immune profiles in sarcoma.

Systemic relapse after radiotherapy and surgery is the major cause of disease-related mortality in sarcoma patients. Combining radiotherapy and immunotherapy is under investigation as a means to improve response rates. However, the immune contexture of sarcoma is understudied. Here, we use a retrospective cohort of sarcoma patients, treated with neoadjuvant radiotherapy, and TCGA data. We explore therapeutic targets of relevance to sarcoma, using genomics and multispectral immunohistochemistry to provide insights into the tumor immune microenvironment across sarcoma subtypes. Differential gene expression between radioresponsive myxoid liposarcoma (MLPS) and more radioresistant undifferentiated pleomorphic sarcoma (UPS) indicated UPS contained higher transcript levels of a number of immunotherapy targets (CD73/NT5E, CD39/ENTPD1, CD25/IL2RA, and 4-1BB/TNFRSF9). We focused on 4-1BB/TNFRSF9 and other costimulatory molecules. In TCGA data, 4-1BB correlated to an inflamed and exhausted phenotype. OX40/TNFRSF4 and 4-1BB/TNFRSF9 were highly expressed in sarcoma subtypes versus other cancers. Despite OX40 and 4-1BB being described as Treg markers, we identified that they delineate distinct tumor immune profiles. This was true for sarcoma and other cancers. While only a limited number of samples could be analyzed, spatial analysis of OX40 expression identified two diverse phenotypes of OX40+ Tregs, one associated with and one independent of tertiary lymphoid structures (TLSs). Patient stratification is of intense interest for immunotherapies. We provide data supporting the viewpoint that a cohort of sarcoma patients, appropriately selected, are promising candidates for immunotherapies. Spatial profiling of OX40+ Tregs, in relation to TLSs, could be an additional metric to improve future patient stratification

Machine-learning of atomic-scale properties based on physical principles

We briefly summarize the kernel regression approach, as used recently in materials modelling, to fitting functions, particularly potential energy surfaces, and highlight how the linear algebra framework can be used to both predict and train from linear functionals of the potential energy, such as the total energy and atomic forces. We then give a detailed account of the Smooth Overlap of Atomic Positions (SOAP) representation and kernel, showing how it arises from an abstract representation of smooth atomic densities, and how it is related to several popular density-based representations of atomic structure. We also discuss recent generalisations that allow fine control of correlations between different atomic species, prediction and fitting of tensorial properties, and also how to construct structural kernels---applicable to comparing entire molecules or periodic systems---that go beyond an additive combination of local environments

Beyond the caveman: Rethinking masculinity in relation to men’s help-seeking

publication-status: Publishedtypes: ArticleStatistically, men make less use of health-care services than women. This has been interpreted as the result of the ‘hegemonic’ masculine code in which ‘real’ men are understood to be physically fit, uninterested in their health and self-reliant. However, less attention has been paid to understanding how hegemonic masculinity intersects with the wider western socio-cultural contexts of men’s help-seeking, particularly the valorization of health as a form of social achievement. This article presents the results of interviews with 14 higher socio-economic status (SES) men to uncover their ‘interpretive repertoires’ in relation to health and illness, help-seeking and masculinity. Although many interviewees drew on the stereotype of the ‘Neanderthal Man’ who avoids the doctors to explain help-seeking by men ‘in general’, they constructed their own experiences of help-seeking in terms of being responsible, problem-solving and in control. It is argued that the framing of help-seeking in terms of ‘taking action’ chimes with an increasingly pro-active ‘expert patient’ approach within western health-care. This conceptual reconstruction of the dominant masculine code in relation to helpseeking, from ‘Neanderthal Man’ to ‘Action Man’, may lead to greater gender equality in terms of accessing health-care. However, it has the potential to exacerbate social inequalities between men from different SES groups

FIP1L1-PDGFRA molecular analysis in the differential diagnosis of eosinophilia

<p>Abstract</p> <p>Background</p> <p>Primary eosinophlia associated with the <it>FIP1L1-PDGFRA </it>rearrangement represents a subset of chronic eosinophilic leukaemia (CEL) and affected patients are very sensitive to imatinib treatment. This study was undertaken in order to examine the prevalence and the associated clinicopathologic and genetic features of <it>FIP1L1-PDGFRA </it>rearrangement in a cohort of 15 adult patients presenting with profound eosinophilia (> 1.5 × 10⁹/L).</p> <p>Methods</p> <p>Reverse transcriptase-polymerase chain reaction (RT-PCR) was used for the detection of <it>FIP1L1-PDGFRA </it>rearrangement and the results confirmed by direct sequencing. <it>C-KIT</it>-D816V mutation was analysed retrospectively by PCR and restriction-fragment-length-polymorphism (PCR-RFLP), in all cases with primary eosinophilia.</p> <p>Results</p> <p>Two male patients with splenomegaly carried the <it>FIP1L1-PDGFRA </it>rearrangement, whilst 2 others were ultimately classified as suffering from idiopathic hypereosinophlic syndrome (HES) and one from systemic mastocytosis. These patients were negative for the <it>C-KIT</it>-D816V mutation and received imatinib (100–400 mg daily). Patients with CEL and HES responded to imatinib and remained in complete haematological, clinical and molecular (for carriers of <it>FIP1L1-PDGFRA </it>rearrangement) remission for a median of 28.2 months (range: 11–54), whilst the patient with systemic mastocytosis did not respond. Interestingly, in both patients with <it>FIP1L1-PDGFRA </it>rearrangement, the breakpoints into <it>PDGFRA </it>were located within exon 12 and fused with exons 8 and 8a of <it>FIP1L1</it>, respectively.</p> <p>Conclusion</p> <p>An early diagnosis of <it>FIPIL1-PDGFRA</it>-positive CEL and imatinib treatment offer to the affected patients an excellent clinical therapeutic result, avoiding undesirable morbidity. Moreover, although the molecular mechanisms underlying disease pathogenesis remain to be determined, imatinib can be effective in patients with idiopathic HES.</p

The plight of the sense-making ape

This is a selective review of the published literature on object-choice tasks, where participants use directional cues to find hidden objects. This literature comprises the efforts of researchers to make sense of the sense-making capacities of our nearest living relatives. This chapter is written to highlight some nonsensical conclusions that frequently emerge from this research. The data suggest that when apes are given approximately the same sense-making opportunities as we provide our children, then they will easily make sense of our social signals. The ubiquity of nonsensical contemporary scientific claims to the effect that humans are essentially--or inherently--more capable than other great apes in the understanding of simple directional cues is, itself, a testament to the power of preconceived ideas on human perception

Galaxy And Mass Assembly (GAMA): the effect of close interactions on star formation in galaxies

The modification of star formation (SF) in galaxy interactions is a complex process, with SF observed to be both enhanced in major mergers and suppressed in minor pair interactions. Such changes likely to arise on short timescales and be directly related to the galaxy-galaxy interaction time. Here we investigate the link between dynamical phase and direct measures of SF on different timescales for pair galaxies, targeting numerous star-formation rate (SFR) indicators and comparing to pair separation, individual galaxy mass and pair mass ratio. We split our sample into the higher (primary) and lower (secondary) mass galaxies in each pair and find that SF is indeed enhanced in all primary galaxies but suppressed in secondaries of minor mergers. We find that changes in SF of primaries is consistent in both major and minor mergers, suggesting that SF in the more massive galaxy is agnostic to pair mass ratio. We also find that SF is enhanced/suppressed more strongly for short-time duration SFR indicators (e.g. H-alpha), highlighting recent changes to SF in these galaxies, which are likely to be induced by the interaction. We propose a scenario where the lower mass galaxy has its SF suppressed by gas heating or stripping, while the higher mass galaxy has its SF enhanced, potentially by tidal gas turbulence and shocks. This is consistent with the seemingly contradictory observations for both SF suppression and enhancement in close pairs

Twelve-month prevalence of haemarthrosis and joint disease using the haemophilia joint health score; evaluation of the UK National Haemophilia Database and Haemtrack patient reported data: an observational study

Objectives: To report the 12 month prevalence of joint bleeds from the national haemophilia database (NHD) and Haemtrack, a patient-reported online treatment diary; and concurrent joint disease status using the haemophilia joint health score (HJHS) at individual joint level, in children and adults with severe haemophilia A and B without a current inhibitor. Design: A 2018 retrospective database study of NHD from which 2238 cases were identified, 463 patients had fully itemised haemophilia joint health scores (HJHS) of whom 273 were compliant in recording treatment using Haemtrack. Setting: England, Wales and Scotland, UK. Participants: Children (<18y) and adults (≥18y) with severe haemophilia A (HA) and B (HB) (FVIII/FIX, <0.01 iu/ml) without a current inhibitor. Primary and secondary outcomes: Prevalence of joint haemarthrosis, and concurrent joint health measured using the Haemophilia Joint Health Scores (HJHS). Results: The median (IQR) age of children was 10 (6-13) and adults 40 (29-50) years. Haemarthrosis prevalence in HA/HB children was 33% and 47%, respectively and 60% and 42%, respectively, in adults. The most common site of haemarthrosis in children was the knee in HA and ankle in HB. In adults, the incidence of haemarthrosis at the ankles and elbows was equal. The median total HJHS in HA/HB children was 0 and in adults with HA/HB, were 18 and 11 respectively. In adults with HA/HB, the median ankle HJHS of 4.0 was higher than the median HJHS of 1.0 for both the knee and elbow. Conclusion; Despite therapeutic advances, only two-thirds of children and one-third of adults were bleed-free, even in a UK cohort selected for high compliance with prophylaxis. The median HJHS of zero in children suggests joint health is relatively unaffected during childhood. In adults, bleed rates were highest in ankles and elbows, but the ankles led to substantially worse joint health scores