julilili42/papers huggingface dataset:
Sideromycins: tools and antibiotics
2009-01-06

Sideromycins are antibiotics covalently linked to siderophores. They are actively transported into gram-positive and gram-negative bacteria. Energy-coupled transport across the outer membrane and the cytoplasmic membrane strongly increases their antibiotic efficiency; their minimal inhibitory concentration is at least 100-fold lower than that of antibiotics that enter cells by diffusion. This is particularly relevant for gram-negative bacteria because the outer membrane, which usually forms a permeability barrier, in this case actively contributes to the uptake of sideromycins. Sideromycin-resistant mutants can be used to identify siderophore transport systems since the mutations are usually in transport genes. Two sideromycins, albomycin and salmycin, are discussed here. Albomycin, a derivative of ferrichrome with a bound thioribosyl-pyrimidine moiety, inhibts seryl-t-RNA synthetase. Salmycin, a ferrioxamine derivative with a bound aminodisaccharide, presumably inhibts protein synthesis. Crystal structures of albomycin bound to the outer membrane transporter FhuA and the periplasmic binding protein FhuD have been determined. Albomycin and salmycin have been used to characterize the transport systems of Escherichia coli and Streptococcus pneumoniae and of Staphylococcus aureus, respectively. The in vivo efficacy of albomycin and salmycin has been examined in a mouse model using Yersinia enterocolitica, S. pneumoniae, and S. aureus infections. Albomycin is effective in clearing infections, whereas salmycin is too unstable to lead to a large reduction in bacterial numbers. The recovery rate of albomycin-resistant mutants is lower than that of the wild-type, which suggests a reduced fitness of the mutants. Albomycin could be a useful antibiotic provided sufficient quantities can be isolated from streptomycetes or synthesized chemically.
Prequips—an extensible software platform for integration, visualization and analysis of LC-MS/MS proteomics data
2009-01-06

Abstract Summary: We describe an integrative software platform, Prequips, for comparative proteomics-based systems biology analysis that: (i) integrates all information generated from mass spectrometry (MS)-based proteomics as well as from basic proteomics data analysis tools, (ii) visualizes such information for various proteomic analyses via graphical interfaces and (iii) links peptide and protein abundances to external tools often used in systems biology studies. Availability: http://prequips.sourceforge.net Contact: dhhwang@postech.ac.kr
Graft Protection in Bypass Surgery: siRNA-Mediated Silencing of Adhesion Molecules
2009-01-06

The outcome of patients after coronary bypass grafting is greatly influenced by the type of graft material employed, especially regarding the rate of graft restenosis. Besides direct thrombotic events, the leukocyte-endothelial interaction modulated by adhesion molecules is identified to be the central cause leading to graft alterations. This study deals with a new therapeutic concept in order to achieve superior protection of a new bypass graft by blocking the adhesion molecule expression pathway with RNA interference to inhibit the initial leukocyte adhesion and transmigration. Leukocyte binding to adhesion molecules on activated human venous endothelial cells (HVECs) was determined by video-assisted microscopy in a flow chamber mimicking physiological conditions. The cells under study were sequentially transfected in a nonviral manner with specific short interfering RNA-sequences (siRNA) targeting E-selectin, intercellular adhesion molecule, and vascular adhesion molecule. After stimulation of adhesion molecule expression by tumor necrosis factor, a leukocyte-rich suspension was run through the chamber and the attaching leukocytes were counted. Transfection with specific siRNA targeting three different adhesion molecules resulted in a highly significant reduction of leukocyte attachment to activated HVECs in each case compared to the controls (p < 0.05). Transfection with a mixture out of all three siRNA-sequences showed the lowest leukocyte adhesion (p < 0.05) compared to the controls. siRNA-sequences inhibit the adhesion molecule expression on HVECs in an extremely effective way; not only in a single transfection of specific molecules but also in a parallel transfection of multiple sequences in one transfection. Accordingly, siRNA treatment significantly reduced adhesion of leukocyte cells to HVECs compared to controls. This study showed for the first time an effective knockdown of the leukocyte-endothelium interactions by transfection of HVECs with a cocktail consisting of three highly specific siRNAs against three different endothelial adhesion molecules.
Characteristics of Responses of Golgi Cells and Mossy Fibers to Eye Saccades and Saccadic Adaptation Recorded from the Posterior Vermis of the Cerebellum
2009-01-07

The anatomical organization of the granular layer of the cerebellum suggests an important function for Golgi cells (GC) in the pathway conveying mossy fiber (MF) afferents to Purkinje cells. Based on such anatomic observations, early proposals have attributed a role in “gain control” for GCs, a function disputed by recent investigations, which assert that GCs instead contribute to oscillatory mechanisms. However, conclusive physiological evidence based on studies of cerebellum-dependent behavior supporting/dismissing the gain control proposition has been lacking as of yet. We addressed the possible function of this interneuron by recording the activity of a large number of both MFs and GCs during saccadic eye movements from the same cortical area of the monkey cerebellum, namely the oculomotor vermis (OMV). Our cellular identification conformed to previously established criteria, mainly to juxtacellular labeling studies correlating physiological parameters with cell morphology. Response patterns of both MFs and GCs were highly heterogeneous. MF discharges correlated linearly with eye saccade metrics and timing, showing directional preference and precise direction tuning. In contrast, GC discharges did not correlate strongly with the metrics or direction of movement. Their discharge properties were also unaffected by motor learning during saccadic adaptation. The OMV therefore receives a barrage of information about eye movements from different oculomotor areas over the MF pathway, which is not reflected in GCs. The unspecificity of GCs has important implications for the intricacies of neuronal processing in the granular layer, clearly discrediting their involvement in gain control and instead suggesting a more secluded role for these interneurons.
Arabidopsis CULLIN3 Genes Regulate Primary Root Growth and Patterning by Ethylene-Dependent and -Independent Mechanisms
2009-01-08

CULLIN3 (CUL3) together with BTB-domain proteins form a class of Cullin-RING ubiquitin ligases (called CRL3s) that control the rapid and selective degradation of important regulatory proteins in all eukaryotes. Here, we report that in the model plant Arabidopsis thaliana, CUL3 regulates plant growth and development, not only during embryogenesis but also at post-embryonic stages. First, we show that CUL3 modulates the emission of ethylene, a gaseous plant hormone that is an important growth regulator. A CUL3 hypomorphic mutant accumulates ACS5, the rate-limiting enzyme in ethylene biosynthesis and as a consequence exhibits a constitutive ethylene response. Second, we provide evidence that CUL3 regulates primary root growth by a novel ethylene-dependant pathway. In particular, we show that CUL3 knockdown inhibits primary root growth by reducing root meristem size and cell number. This phenotype is suppressed by ethylene-insensitive or resistant mutations. Finally, we identify a function of CUL3 in distal root patterning, by a mechanism that is independent of ethylene. Thus, our work highlights that CUL3 is essential for the normal division and organisation of the root stem cell niche and columella root cap cells.
Changes in the effective gravitational field strength affect the state of phosphorylation of stress-related proteins in callus cultures of Arabidopsis thaliana
2009-01-08

In a recent study it was shown that callus cell cultures of Arabidopsis thaliana respond to changes in gravitational field strengths by changes in protein expression. Using ESI-MS/MS for proteins with differential abundance after separation by 2D-PAGE, 28 spots which changed reproducibly and significantly in amount (P <0.05) after 2 h of hypergravity (18 up-regulated, 10 down-regulated) could be identified. The corresponding proteins were largely involved in stress responses, including the detoxification of reactive oxygen species (ROS). In the present study, these investigations are extended to phosphorylated proteins. For this purpose, callus cell cultures of Arabidopsis thaliana were exposed to hypergravity (8 g) and simulated weightlessness (random positioning; RP) for up to 30 min, a period of time which yielded the most reliable data. The first changes, however, were visible as early as 10 min after the start of treatment. In comparison to 1 g controls, exposure to hypergravity resulted in 18 protein spots, and random positioning in 25, respectively, with increased/decreased signal intensity by at least 2-fold (P <0.05). Only one spot (alanine aminotransferase) responded the same way under both treatments. After 30 min of RP, four spots appeared, which could not be detected in control samples. Among the protein spots altered in phosphorylation, it was possible to identify 24 from those responding to random positioning and 12 which responded to 8 g. These 12 proteins (8 g) are partly (5 out of 12) the same as those changed in expression after exposure to 2 h of hypergravity. The respective proteins are involved in scavenging and detoxification of ROS (32%), primary metabolism (20.5%), general signalling (14.7%), protein translation and proteolysis (14.7%), and ion homeostasis (8.8%). Together with our recent data on protein expression, it is assumed that changes in gravitational fields induce the production of ROS. Our data further indicate that responses toward RP are more by post-translational protein modulation (most changes in the degree of phosphorylation occur under RP-treatment) than by protein expression (hypergravity).
In conditions of limited chromophore supply rods entrap 11-cis-retinal leading to loss of cone function and cell death
2009-01-08

RPE65 is a retinoid isomerase required for the production of 11-cis-retinal, the chromophore of both cone and rod visual pigments. We recently established an R91W knock-in mouse strain as homologous animal model for patients afflicted by this mutation in RPE65. These mice have impaired vision and can only synthesize minute amounts of 11-cis-retinal. Here, we investigated the consequences of this chromophore insufficiency on cone function and pathophysiology. We found that the R91W mutation caused cone opsin mislocalization and progressive geographic cone atrophy. Remnant visual function was mostly mediated by rods. Ablation of rod opsin corrected the localization of cone opsin and improved cone retinal function. Thus, our analyses indicate that under conditions of limited chromophore supply rods and cones compete for 11-cis-retinal that derives from regeneration pathway(s) which are reliant on RPE65. Due to their higher number and the instability of cone opsin, rods are privileged under this condition while cones suffer chromophore deficiency and degenerate. These findings reinforce the notion that in patients any effective gene therapy with RPE65 needs to target the cone-rich macula directly to locally restore the cones' chromophore supply outside the reach of rods.
ChemInform Abstract: Genoketides A1 (I) and A2 (II), New Octaketides and Biosynthetic Intermediates of Chrysophanol Produced by Streptomyces sp. AK 671.
2009-01-08

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Improvement of reading speed after providing of low vision aids in patients with age‐related macular degeneration
2009-01-09

Abstract. Purpose: Age‐related macular degeneration (AMD) is the most common cause of severe visual impairment, including loss of reading ability, among elderly persons in developed countries. The aim of the present study was to evaluate reading ability before and after providing of appropriate low vision aids. Methods: Five hundred and thirty patients with different stages of AMD (age 82 ± 8 years) were included in this retrospective study. All patients underwent a standardized ophthalmological examination including evaluation of magnification requirement and careful providing of low vision aids. Before and after the provision of low vision aids, reading speed [words per minute (wpm)] was evaluated using standardized reading texts. Results: For the whole group, the average best‐corrected distance visual acuity of the better eye was 0.18 ± 0.15, with 69% of patients having visual acuity of 0.1 (20/200) or better. The mean magnification requirement was 7.4 ± 6.3‐fold (range 2–25). Visual rehabilitation was achieved with optical visual aids in 58% of patients, whereas 42% of patients needed electronically closed‐circuit TV systems. Mean reading speed was 20 ± 33 wpm before and increased significantly to 72 ± 35 (p &lt; 0.0001) after the provision of low vision aids for the whole group. Between patients with visual acuity &lt; 0.1 and patients with visual acuity of 0.1 or better, there are highly significant differences in reading speed before (0.4 ± 3.8 versus 20 ± 28 wpm, p ≤ 0.0001) and after providing of visual aids (40 ± 13 versus 84 ± 30 wpm, p ≤ 0.0001). Patients with severe visual impairment (visual acuity ≤ 0.1) showed significantly lower improvement of reading speed compared to patients with visual acuity of 0.1 or better following rehabilitation (p ≤ 0.0001). Before providing of low vision aids, only 16% of patients were able to read; in contrast, reading ability was achieved in 94% of patients after the provision of low vision aids for the whole group. Conclusion: Our results indicate the great value of low vision rehabilitation through adequate providing of vision aids for the improvement of reading ability, with a highly significant increase of reading speed without training of eccentric viewing in patients with retained central fixation. The prompt implementation of low vision aids in patients with macular degeneration will help them to maintain and regain their reading ability, which can lead to an increase in independence, communication, mental agility and quality of life.
A SEARCH FOR A DARK MATTER ANNIHILATION SIGNAL TOWARD THE CANIS MAJOR OVERDENSITY WITH H.E.S.S.
2009-01-09

A search for a dark matter (DM) annihilation signal into -rays toward the direction of the Canis Major (CMa) overdensity is presented. The nature of CMa is still controversial and one scenario represents it as a dwarf galaxy, making it an interesting candidate for DM annihilation searches. A total of 9.6 hours of high quality data were collected with the H.E.S.S. array of Imaging Atmospheric Cherenkov Telescopes (IACTs) and no evidence for a very high energy -ray signal is found. Upper limits on the CMa dwarf galaxy mass of the order of 10 M are derived at the 95% C.L. assuming neutralino masses in the range 500 GeV - 10 TeV and relatively large annihilation cross-sections. Constraints on the velocity-weighted annihilation cross section , are calculated for specific WIMP scenarios, using a NFW model for the DM halo profile and taking advantage of numerical simulations of hierarchical structure formation. 95% C.L. exclusion limits of the order of 5 10 cm s are reached in the 500 GeV - 10 TeV DM particle mass interval, assuming a total halo mass of 3 10 M .
Facile, economical and direct synthesis of 9-anilinoacridines
2009-01-10

Acridines are well-known group of compounds with a wide variety of biological properties. We describe herein an expeditious approach to prepare anilinoacridine derivatives from mefenamic acid. It is the first report of a one-pot approach to anilinoacridines in good to excellent yields.
The mitochondrial genome sequence of the Tasmanian tiger (Thylacinus cynocephalus)
2009-01-12

We report the first two complete mitochondrial genome sequences of the thylacine ( Thylacinus cynocephalus ), or so-called Tasmanian tiger, extinct since 1936. The thylacine's phylogenetic position within australidelphian marsupials has long been debated, and here we provide strong support for the thylacine's basal position in Dasyuromorphia, aided by mitochondrial genome sequence that we generated from the extant numbat ( Myrmecobius fasciatus ). Surprisingly, both of our thylacine sequences differ by 11%–15% from putative thylacine mitochondrial genes in GenBank, with one of our samples originating from a direct offspring of the previously sequenced individual. Our data sample each mitochondrial nucleotide an average of 50 times, thereby providing the first high-fidelity reference sequence for thylacine population genetics. Our two sequences differ in only five nucleotides out of 15,452, hinting at a very low genetic diversity shortly before extinction. Despite the samples’ heavy contamination with bacterial and human DNA and their temperate storage history, we estimate that as much as one-third of the total DNA in each sample is from the thylacine. The microbial content of the two thylacine samples was subjected to metagenomic analysis, and showed striking differences between a wild-captured individual and a born-in-captivity one. This study therefore adds to the growing evidence that extensive sequencing of museum collections is both feasible and desirable, and can yield complete genomes.
Immunosenescence and Vaccination in Nursing Home Residents
2009-01-13

The elderly population continues to increase in most countries. Concomitantly, the number of individuals who are institutionalized is also increasing, unfortunately, with more and more individuals being institutionalized at greater ages. These elderly individuals are very different from healthy, community-dwelling elderly individuals, in that many are considered to be frail and have various chronic diseases. It is apparent that the immune response diminishes even in healthy elderly people and that the pathologies that occur in nursing home patients, together with malnutrition, further impair immunity required for an effective vaccine response. Therefore, it is important to take secondary age-related effects, attributable to factors such as chronic diseases, inflammation, frailty, nutrition, functional status, and stress, into account when assessing vaccination strategies. Despite these alterations that can affect immune function and their potential interaction with vaccination, vaccination is still worthwhile and is recommended for elderly nursing home residents. Research efforts should continue attempts to elucidate the immunological basis of impaired immunity in nursing home residents to design improved prevention strategies for this vulnerable group.
cGMP‐dependent protein kinase II and aldosterone secretion
2009-01-13

ACTH‐stimulated aldosterone secretion can be inhibited by atrio‐natriuretic peptide/cGMP. The mechanism behind this modulation has been reported to involve cGMP‐dependent activation of phosphodiesterase 2 (PDE2) and hydrolysis of cAMP. Recently it was reported that activation of cGMP‐dependent protein kinase II (cGKII) stimulated aldosterone secretion in rat zona glomerulosa cells. The zona glomerulosa of the murine adrenal cortex expresses cGKII and PDE2. We used mice with a homozygous inactivation of the cGKII gene to investigate in vivo the potential role of this kinase in aldosterone secretion. Basal plasma renin and aldosterone levels were similar in wild‐type and cGKII −/− mice. In vivo injection of atrio‐natriuretic peptide decreased ACTH‐stimulated aldosterone secretion in wild‐type mice, but had no effect in cGKII‐deficient mice. These results support the view that cGKII modulates aldosterone secretion in the murine adrenal cortex.
The Versatility of Solid‐State Metathesis Reactions: From Rare Earth Fluorides to Carbodiimides
2009-01-13

Abstract The new carbodiimide compounds LaF(CN 2 ) and LiPr 2 F 3 (CN 2 ) 2 were obtained as crystalline powders by solid‐state metathesis reactions from 1:1 molar ratios of RE F 3 ( RE = rare earth) and Li 2 (CN 2 ) at temperatures between 500 and 700 °C over 4 days in fused copper ampoules. Higher proportions of Li 2 (CN 2 ) in reactions yielded RE 2 (CN 2 ) 3 compounds, including the new Eu 2 (CN 2 ) 3 . Single‐crystal structure refinements were performed for LaF(CN 2 ) and LiPr 2 F 3 (CN 2 ) 2 . Homologous Li RE 2 F 3 (CN 2 ) 2 compounds with RE = Ce, Pr, Nd, Sm, Eu, Gd were assigned by isotypic indexing of their XRD patterns. The crystal structure of LaF(CN 2 ) contains planar [La 3 F 3 ] layers being interconnected by carbodiimide ions, and is related with that of the mineral bastnäsite ( RE F(CO 3 )).
Analysis of Two KCNJ11 Neonatal Diabetes Mutations, V59G and V59A, and the Analogous KCNJ8 I60G Substitution
2009-01-13

beta-Cell-type K(ATP) channels are octamers assembled from Kir6.2/KCNJ11 and SUR1/ABCC8. Adenine nucleotides play a major role in their regulation. Nucleotide binding to Kir6.2 inhibits channel activity, whereas ATP binding/hydrolysis on sulfonylurea receptor 1 (SUR1) opposes inhibition. Segments of the Kir6.2 N terminus are important for open-to-closed transitions, form part of the Kir ATP, sulfonylurea, and phosphoinositide binding sites, and interact with L0, an SUR cytoplasmic loop. Inputs from these elements link to the pore via the interfacial helix, which forms an elbow with the outer pore helix. Mutations that destabilize the interfacial helix increase channel activity, reduce sensitivity to inhibitory ATP and channel inhibitors, glibenclamide and repaglinide, and cause neonatal diabetes. We compared Kir6.x/SUR1 channels carrying the V59G substitution, a cause of the developmental delay, epilepsy, and neonatal diabetes syndrome, with a V59A substitution and the equivalent I60G mutation in the related Kir6.1 subunit from vascular smooth muscle. The substituted channels have increased P(O) values, decreased sensitivity to inhibitors, and impaired stimulation by phosphoinositides but retain sensitivity to Ba(2+)-block. The V59G and V59A channels are either not, or poorly, stimulated by phosphoinositides, respectively. Inhibition by sequestrating phosphatidylinositol 4,5-bisphosphate with neomycin and polylysine is reduced in V59A, and abolished in V59G channels. Stimulation by SUR1 is intact, and increasing the concentration of inhibitory ATP restores the sensitivity of Val-59-substituted channels to glibenclamide. The I60G channels, strongly dependent on SUR stimulation, remain sensitive to sulfonylureas. The results suggest the interfacial helix dynamically links inhibitory inputs from the Kir N terminus to the gate and that sulfonylureas stabilize an inhibitory configuration.
2009-01-13

cyclopentanering is discussed in some detail.The literature concerning the determination of structure, configuration and conformation of iridoids is re-Unter Iridoiden versteht man Monoviewed.The use of NMR spectroscopy terpene mit einem Hexahydro-cyclofor the determination of configuration penta[c]pyran-Ringsystem und davon and preferred conformation of the ableitbare Verbindungen.Die
2009-01-13

Enzymes for the biosyntheses of the major phenylpropanoid derivatives in vascular plants, namely flavonoids, lignins and cinnamyl esters are now known.The cinnamate pathway to these compounds is reviewed briefly and brought up-to-date.Remaining problems, such as the regulation by light and other factors as well as compartmentalization of phenylpropanoid metabolism are being studied in many laboratories.The physiological importance of low molecular weight cinnamyl compounds needs attention.Pioneer tracer studies by the schools of NEISH [24], FREUDENBERG [24] and