Anthocyanins acylated with gallic acid from chenille plant, Acalypha hispida

Three anthocyanins were isolated from the red flowers of chenille plant, Acalypha hispida Burm. (Euphorbiaceae) by a combination of chromatographic techniques. Their structures were elucidated mainly by homo- and heteronuclear nuclear magnetic resonance spectroscopy and electrospray mass spectrometry, and supported with complete assignments of 13C NMR resonances. The novel pigment, cyanidin 3-O-(2"-galloyl-6"-O-alpha-rhamnopyranosyl-beta-galactopyranoside) (5%), contains the disaccharide robinoside. The other anthocyanins were identified as cyanidin 3-O-(2"-galloyl-beta-galactopyranoside) (85%), and cyanidin 3-O-beta-galactopyranoside (5%). Anthocyanins acylated with gallic acid have previously been identified in species from the families Nymphaeaceae and Aceraceae, and tentatively in Abrus precatorius (Leguminosae).     

Evidence for the presence of the glyoxylate cycle in Chloroflexus

The key enzymes of the glyoxylate cycle, isocitrate lyase and malate synthase, were present in cell-free extracts of the phototrophic, green, thermophilic bacterium Chloroflexus aurantiacus grown with acetate as the sole organic carbon source.The optimum temperature of these enzymes was 40° C, and their specific activities were high enough to account for the observed growth rate. Lower levels of the enzymes were found in extracts from cells grown on a complete medium.Itaconate was shown to inhibit isocitrate lyase from C. aurantiacus 96% at a concentration of 0.25 mM and also had a profound effect on the growth of the organism on acetate, 0.25 mM inhibiting completely. Itaconate also inhibited the growth when added to the complex medium, but in this case much higher concentrations were required.     

Removal of acidic residues of the prodomain of PCSK9 increases its activity towards the LDL receptor

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low density lipoprotein receptor (LDLR) at the cell surface and mediates intracellular degradation of the LDLR. The amino-terminus of mature PCSK9, residues 31–53 of the prodomain, has an inhibitory effect on this function of PCSK9, but the underlying mechanism is not fully understood. In this study, we have identified two highly conserved negatively charged segments (residues 32–40 and 48–50, respectively) within this part of the prodomain and performed deletions and substitutions to study their importance for degradation of the LDLRs.Deletion of the acidic residues of the longest negatively charged segment increased PCSK9’s ability to degrade the LDLR by 31%, whereas a modest 8% increase was observed when these residues were mutated to uncharged amino acids. Thus, both the length and the charge of this part of the prodomain were important for its inhibitory effect. Deletion of the residues of the shorter second negatively charged segment only increased PCSK9’s activity by 8%. Substitution of the amino acids of both charged segments to uncharged residues increased PCSK9’s activity by 36%. These findings indicate that the inhibitory effect of residues 31–53 of the prodomain is due to the negative charge of this segment. The underlying mechanism could involve the binding of this peptide segment to positively charged structures which are important for PCSK9’s activity. One possible candidate could be the histidine-rich C-terminal domain of PCSK9.     

Elimination of thermodynamically infeasible loops in steady-state metabolic models

The constraint-based reconstruction and analysis (COBRA) framework has been widely used to study steady-state flux solutions in genome-scale metabolic networks. One shortcoming of current COBRA methods is the possible violation of the loop law in the computed steady-state flux solutions. The loop law is analogous to Kirchhoff's second law for electric circuits, and states that at steady state there can be no net flux around a closed network cycle. Although the consequences of the loop law have been known for years, it has been computationally difficult to work with. Therefore, the resulting loop-law constraints have been overlooked. Here, we present a general mixed integer programming approach called loopless COBRA (ll-COBRA), which can be used to eliminate all steady-state flux solutions that are incompatible with the loop law. We apply this approach to improve flux predictions on three common COBRA methods: flux balance analysis, flux variability analysis, and Monte Carlo sampling of the flux space. Moreover, we demonstrate that the imposition of loop-law constraints with ll-COBRA improves the consistency of simulation results with experimental data. This method provides an additional constraint for many COBRA methods, enabling the acquisition of more realistic simulation results.     

Record of a new northern range of Sowerby's beaked whale (Mesoplodon bidens )

Two beaked whales identified as Sowerby's beaked whale (Mesoplodon bidens) were observed in sea state 0–1 on 16 July 1995 at 71°30′N 04°00′E in the Norwegian Sea. A number of morphological features, such as dentition, were clearly seen during the encounter. The Sowerby's beaked whale's core distribution is in the North Sea and the previous northernmost sighting was made at 63°06′N 00°41′E. According to the literature, the species has never been recorded in the polar zone. The sighting in the Norwegian Sea suggests that the current data on the species distribution is uncertain, and that its range may include the polar waters of the Norwegian Sea. Received: 24 April 1996 / Accepted: 25 August 1996     

Untangling the intracellular signalling network in cancer--a strategy for data integration in acute myeloid leukaemia

Protein and gene networks centred on the regulatory tumour suppressor proteins may be of crucial importance both in carcinogenesis and in the response to chemotherapy. Tumour suppressor protein p53 integrates intracellular data in stress responses, receiving signals and translating these into differential gene expression. Interpretation of the data integrated on p53 may therefore reveal the response to therapy in cancer. Proteomics offers more specific data - closer to "the real action" - than the hitherto more frequently used gene expression profiling. Integrated data analysis may reveal pathways disrupted at several regulatory levels. Ultimately, integrated data analysis may also contribute to finding key underlying cancer genes. We here proposes a Partial Least Squares Regression (PLSR)-based data integration strategy, which allows simultaneous analysis of proteomic data, gene expression data and classical clinical parameters. PLSR collapses multidimensional data into fewer relevant dimensions for data interpretation. PLSR can also aid identification of functionally important modules by also performing comparison to databases on known biological interactions. Further, PLSR allows meaningful visualization of complex datasets, aiding interpretation of the underlying biology. Extracting the true biological causal mechanisms from heterogeneous patient populations is the key to discovery of new therapeutic options in cancer.     

A century of conservation: The ongoing recovery of Svalbard reindeer

Several caribou and reindeer (Rangifer tarandus) populations have experienced recent population declines, often attributed to anthropogenic stressors such as harvesting, landscape fragmentation, and climate change. Svalbard reindeer (R. t. platyrhynchus), the wild reindeer subspecies endemic to the high-Arctic Svalbard archipelago, was protected in 1925, after most subpopulations had been eradicated by harvest. Although direct pressure from harvest has ceased, indirect anthropogenic stressors from environmental changes have increased in this climate change hot spot. An assessment of the current distribution and abundance is therefore urgently needed. We combined distance sampling (300 km transects, n = 489 reindeer groups) and total counts (1,350 km², n = 1,349 groups) to estimate the Svalbard reindeer distribution and abundance across its entire range, which we compared with historical data from the literature and radiocarbon-dated bones. Reindeer have now recolonized nearly all non-glaciated land (i.e., areas occupied prior to human presence), and their spatial variation in abundance reflects vegetation productivity. Independent of vegetation productivity, however, recently recolonized areas have lower reindeer densities than areas not subject to past extirpation. This suggests that recovery from past overharvesting is still in progress. These incompletely recovered areas are potential targets for increased monitoring frequency and maintaining strict conservation to follow the Svalbard management goal (i.e., virtually untouched wilderness areas). Because of such ongoing recolonization, possibly combined with vegetation greening effects of recent warming, our status estimate of Svalbard reindeer abundance (22,435 [95% CI = 21,452–23,425]) is more than twice a previous estimate based on opportunistic counts. Thus, although our study demonstrates the successful outcome of strict harvesting control implemented a century ago, current and future population trajectories are likely shaped by climate change. © 2019 The Authors. Journal of Wildlife Management Published by Wiley Periodicals, Inc. on behalf of The Wildlife Society.     

Host genetic requirements for DNA release of lactococcal phage TP901-1

The first step in phage infection is the recognition of, and adsorption to, a receptor located on the host cell surface. This reversible host adsorption step is commonly followed by an irreversible event, which involves phage DNA delivery or release into the bacterial cytoplasm. The molecular components that trigger this latter event are unknown for most phages of Gram-positive bacteria. In the current study, we present a comparative genome analysis of three mutants of Lactococcus cremoris 3107, which are resistant to the P335 group phage TP901-1 due to mutations that affect TP901-1 DNA release. Through genetic complementation and phage infection assays, a predicted lactococcal three-component glycosylation system (TGS) was shown to be required for TP901-1 infection. Major cell wall saccharidic components were analysed, but no differences were found. However, heterologous gene expression experiments indicate that this TGS is involved in the glucosylation of a cell envelope-associated component that triggers TP901-1 DNA release. To date, a saccharide modification has not been implicated in the DNA delivery process of a Gram-positive infecting phage.