Lipogenesis and redox balance in nitrogen-fixing pea bacteroids

Within legume root nodules, rhizobia differentiate into bacteroids that oxidise host-derived dicarboxylic acids, which is assumed to occur via the TCA-cycle to generate NAD(P)H for reduction of N2. Metabolic flux analysis of laboratory grown Rhizobium leguminosarum showed that the flux from 13C-succinate was consistent with respiration of an obligate aerobe growing on a TCA-cycle intermediate as the sole carbon source. However, the instability of fragile pea bacteroids prevented their steady state labelling under N2-fixing conditons. Therefore, comparitive metabolomic profiling was used to compare free-living R. leguminosarum with pea bacteroids. While the TCA-cycle was shown to be essential for maximal rates of N2-fixation, pyruvate (5.5-fold down), acetyl-CoA (50-fold down), free coenzyme A (33-fold) and citrate (4.5-fold down) were much lower in bacteroids. Instead of completely oxidising acetyl-CoA, pea bacteroids channel it into both lipid and the lipid-like polymer poly-β-hydroxybutyrate (PHB), the latter via a type II PHB synthase that is only active in bacteroids. Lipogenesis may be a fundamental requirement of the redox poise of electron donation to N2 in all legume nodules. Direct reduction by NAD(P)H of the likely electron donors for nitrogenase, such as ferredoxin, is inconsistent with their redox potentials. Instead, bacteroids must balance the production of NAD(P)H from oxidation of acetyl-CoA in the TCA-cycle with its storage in PHB and lipids

Comparison of ammonia emissions related to nitrogen use efficiency of livestock production in Europe

The increasing global demand for food and the environmental effects of reactive nitrogen losses in the food production chain, increase the need for efficient use of nitrogen (N). Of N harvested in agricultural plant products, 80% is used to feed livestock. Because the largest atmospheric loss of reactive nitrogen from livestock production systems is ammonia (NH3), the focus of this paper is on N lost as NH3 during the production of animal protein. The focus of this paper is to understand the key factors explaining differences in Nitrogen Use Efficiency (NUE) of animal production among various European countries. Therefore we developed a conceptual framework to describe the NUE defined as the amount of animal-protein N per N in feed and NH3–N losses in the production of milk, beef, pork, chicken meat and eggs in The Netherlands, Switzerland, United Kingdom, Germany, Austria and Denmark. The framework describes how manure management and animal-related parameters (feed, metabolism) relate to NH3 emissions and NUE. The results showed that the animal product with the lowest NUE had the largest NH3 emissions and vice versa, which agrees with the reciprocal relationship between NUE and NH3 within the conceptual framework. Across animal products for the countries considered, about 20% of the N in feed is lost as NH3. The significant smallest proportion (12%) of NH3–N per unit of Nfeed is from chicken production. The proportions for other products are 17%, 19%, 20% and 22% for milk, pork, eggs and beef respectively. These differences were not significantly different due to the differences among countries. For all countries, NUE was lowest for beef and highest for chicken. The production of 1 kg N in beef required about 5 kg N in feed, of which 1 kg N was lost as NH3–N. For the production of 1 kg N in chicken meat, 2 kg N in feed was required and 0.2 kg was lost as NH3. The production of 1 kg N in milk required 4 kg N in feed with 0.6 kg NH3–N loss, the same as pork and eggs, but those needed 3 and 3.5 kg N in feed per kg N in product respectively. Except for beef, the differences among these European countries were mainly caused by differences in manure management practices and their emission factors, rather than by animal-related factors including feed and digestibility influencing the excreted amount of ammoniacal N (TAN). For beef, both aspects caused important differences. Based on the results, we encourage the expression of N losses as per N in feed or per N in product, in addition to per animal place, when comparing production efficiency and NUE. We consider that disaggregating emission factors into a diet/animal effect and a manure management effect would improve the basis for comparing national NH3 emission inventories. © 2018 The Author

Synthesis and characterisation of novel fluorescent imides by a rhodium(III)-catalysed C-H activation/annulation cascade

Regioselective rhodium(III)-catalysed C-H activation/annulation of O-pivaloyl benzoylhydroxamates with ortho-alkynylbenzoate esters facilitates the rapid preparation of a novel class of fluorophores based on the isoindolo[2,1-b]isoquinoline-5,7-dione core. The photophysical, electrochemical and coordination properties of these novel structures are investigated

Phenotypic spectrum in osteogenesis imperfecta due to mutations in TMEM38B: unravelling a complex cellular defect.

Context: Recessive mutations in TMEM38B cause type XIV osteogenesis imperfecta (OI) by dysregulating intracellular calcium flux. Objectives: Clinical and bone material phenotype description and osteoblast differentiation studies. Design and Setting: Natural history study in paediatric research centres. Patients: Eight patients with type XIV OI. Main Outcome Measures: Clinical examinations included: bone mineral density, radiographs, echocardiography and muscle biopsy. Bone biopsy samples (n=3) were analysed using histomorphometry, quantitative backscattered electron microscopy and Raman microspectroscopy. Cellular differentiation studies were performed on proband and control osteoblasts and normal murine osteoclasts. Results: The clinical phenotype of type XIV OI ranges from asymptomatic to severe. Previously unreported features include vertebral fractures, periosteal cloaking, coxa vara and extraskeletal features (muscular hypotonia, cardiac abnormalities). Proband L1-L4 bone density Z-score was reduced (median -3.3 [range -4.77 to +0.1; n=7]), and increased by +1.7 (1.17 to 3.0; n=3) following bisphosphonate therapy. TMEM38B mutant bone has reduced trabecular bone volume, osteoblast and particularly osteoclast numbers, with >80% reduction in bone resorption. Bone matrix mineralization is normal and nanoporosity low. We demonstrate a complex osteoblast differentiation defect with decreased expression of early markers and increased late and mineralization-related markers. Predominance of TRIC-B over TRIC-A expression in murine osteoclasts supports an intrinsic osteoclast defect underlying low bone turnover. Conclusions: OI type XIV has a bone histology, matrix mineralization and osteoblast differentiation pattern that is distinct from OI with collagen defects. Probands are responsive to bisphosphonates and some show muscular and cardiovascular features possibly related to intracellular calcium flux abnormalities

Chaotic scalar fields as models for dark energy

We consider stochastically quantized self-interacting scalar fields as suitable models to generate dark energy in the universe. Second quantization effects lead to new and unexpected phenomena is the self interaction strength is strong. The stochastically quantized dynamics can degenerate to a chaotic dynamics conjugated to a Bernoulli shift in fictitious time, and the right amount of vacuum energy density can be generated without fine tuning. It is numerically observed that the scalar field dynamics distinguishes fundamental parameters such as the electroweak and strong coupling constants as corresponding to local minima in the dark energy landscape. Chaotic fields can offer possible solutions to the cosmological coincidence problem, as well as to the problem of uniqueness of vacua.Comment: 30 pages, 3 figures. Replaced by final version accepted by Phys. Rev.

Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts

BACKGROUND: The magnitude of the association between Helicobacter pylori and incidence of gastric cancer is unclear. H pylori infection and the circulating antibody response can be lost with development of cancer; thus retrospective studies are subject to bias resulting from classifi- cation of cases as H pylori negative when they were infected in the past. AIMS: To combine data from all case control studies nested within prospective cohorts to assess more reliably the relative risk of gastric cancer associated with H pylori infection.To investigate variation in relative risk by age, sex, cancer type and subsite, and interval between blood sampling and cancer diagnosis. METHODS: Studies were eligible if blood samples for H pylori serology were collected before diagnosis of gastric cancer in cases. Identified published studies and two unpublished studies were included. Individual subject data were obtained for each. Matched odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for the association between H pylori and gastric cancer. RESULTS: Twelve studies with 1228 gastric cancer cases were considered. The association with H pylori was restricted to noncardia cancers (OR 3.0; 95% CI 2.3–3.8) and was stronger when blood samples for H pylori serology were collected 10+ years before cancer diagnosis (5.9; 3.4–10.3). H pylori infection was not associated with an altered overall risk of cardia cancer (1.0; 0.7–1.4). CONCLUSIONS: These results suggest that 5.9 is the best estimate of the relative risk of non-cardia cancer associated with H pylori infection and that H pylori does not increase the risk of cardia cancer. They also support the idea that when H pylori status is assessed close to cancer diagnosis, the magnitude of the non-cardia association may be underestimated

Intrinsic Defect in T Cell Production of Interleukin (IL)-13 in the Absence of Both IL-5 and Eotaxin Precludes the Development of Eosinophilia and Airways Hyperreactivity in Experimental Asthma

Interleukin (IL)-5 and IL-13 are thought to play key roles in the pathogenesis of asthma. Although both cytokines use eotaxin to regulate eosinophilia, IL-13 is thought to operate a separate pathway to IL-5 to induce airways hyperreactivity (AHR) in the allergic lung. However, identification of the key pathway(s) used by IL-5 and IL-13 in the disease process is confounded by the failure of anti–IL-5 or anti–IL-13 treatments to completely inhibit the accumulation of eosinophils in lung tissue. By using mice deficient in both IL-5 and eotaxin (IL-5/eotaxin−/−) we have abolished tissue eosinophilia and the induction of AHR in the allergic lung. Notably, in mice deficient in IL-5/eotaxin the ability of CD4+ T helper cell (Th)2 lymphocytes to produce IL-13, a critical regulator of airways smooth muscle constriction and obstruction, was significantly impaired. Moreover, the transfer of eosinophils to IL-5/eotaxin−/− mice overcame the intrinsic defect in T cell IL-13 production. Thus, factors produced by eosinophils may either directly or indirectly modulate the production of IL-13 during Th2 cell development. Our data show that IL-5 and eotaxin intrinsically modulate IL-13 production from Th2 cells and that these signaling systems are not necessarily independent effector pathways and may also be integrated to regulate aspects of allergic disease

Comparison of ammonia emissions related to nitrogen use efficiency of livestock production in Europe

The increasing global demand for food and the environmental effects of reactive nitrogen losses in the food production chain, increase the need for efficient use of nitrogen (N). Of N harvested in agricultural plant products, 80% is used to feed livestock. Because the largest atmospheric loss of reactive nitrogen from livestock production systems is ammonia (NH3), the focus of this paper is on N lost as NH3 during the production of animal protein. The focus of this paper is to understand the key factors explaining differences in Nitrogen Use Efficiency (NUE) of animal production among various European countries. Therefore we developed a conceptual framework to describe the NUE defined as the amount of animal-protein N per N in feed and NH3-N losses in the production of milk, beef, pork, chicken meat and eggs in The Netherlands, Switzerland, United Kingdom, Germany, Austria and Denmark. The framework describes how manure management and animal-related parameters (feed, metabolism) relate to NH3 emissions and NUE. The results showed that the animal product with the lowest NUE had the largest NH3 emissions and vice versa, which agrees with the reciprocal relationship between NUE and NH3 within the conceptual framework. Across animal products for the countries considered, about 20% of the N in feed is lost as NH3. The significant smallest proportion (12%) of NH3-N per unit of Nfeed is from chicken production. The proportions for other products are 17%, 19%, 20% and 22% for milk, pork, eggs and beef respectively. These differences were not significantly different due to the differences among countries. For all countries, NUE was lowest for beef and highest for chicken. The production of 1 kg N in beef required about 5 kg N in feed, of which 1 kg N was lost as NH3-N. For the production of 1 kg N in chicken meat, 2 kg N in feed was required and 0.2 kg was lost as NH3. The production of 1 kg N in milk required 4 kg N in feed with 0.6 kg NH3-N loss, the same as pork and eggs, but those needed 3 and 3.5 kg N in feed per kg N in product respectively. Except for beef, the differences among these European countries were mainly caused by differences in manure management practices and their emission factors, rather than by animal-related factors including feed and digestibility influencing the excreted amount of ammoniacal N (TAN). For beef, both aspects caused important differences. Based on the results, we encourage the expression of N losses as per N in feed or per N in product, in addition to per animal place, when comparing production efficiency and NUE. We consider that disaggregating emission factors into a diet/animal effect and a manure management effect would improve the basis for comparing national NH3 emission inventories

Surface-wave imaging of the weakly-extended Malawi Rift from ambient-noise and teleseismic Rayleigh waves from onshore and lake-bottom seismometers

Located at the southernmost sector of the Western Branch of the East African Rift System, the Malawi Rift exemplifies an active, magma-poor, weakly extended continental rift. To investigate the controls on rifting, we image crustal and uppermost mantle structure beneath the region using ambient-noise and teleseismic Rayleigh-wave phase velocities between 9 and 100 s period. Our study includes six lake-bottom seismometers located in Lake Malawi (Nyasa), the first time seismometers have been deployed in any of the African rift lakes. Noise-levels in the lake are lower than that of shallow oceanic environments and allow successful application of compliance corrections and instrument orientation determination. Resulting phase-velocity maps reveal slow velocities primarily confined to Lake Malawi at short periods (T 25 s) a prominent low-velocity anomaly exists beneath the Rungwe Volcanic Province at the northern terminus of the rift basin. Estimates of phase-velocity sensitivity indicates these low velocities occur within the lithospheric mantle and potentially uppermost asthenosphere, suggesting that mantle processes may control the association of volcanic centers and the localization of magmatism. Beneath the main portion of the Malawi Rift, a modest reduction in velocity is also observed at periods sensitive to the crust and upper mantle, but these velocities are much higher than those observed beneath Rungwe