bluuebunny/crossref_metadata_2025 huggingface dataset:
SGS Database: use of relational databases to enhance data management for multi-site experiments
Authors: Scott J. M. , Lord C. J.
Published: December 2005

Relational databases are increasingly used to manage large and complex experimental datasets. This technology was chosen to create a common database tool for a large multi-site experiment which measured aspects of the sustainability of various regionally focused grazing experiments, as part of the Sustainable Grazing Systems Program. Since the data needs of experiments expanded over time and the number of sites and subsites increased, it was necessary to adopt an evolutionary approach to creating the database. It was important that the database be customised to accommodate the wide range of experiments and the diverse needs of the many scientists involved and yet have complete conformity of structure to permit across-site queries. This paper describes the steps taken in this process and suggests how similar database projects could be implemented more efficiently in the future. As most of the scientists involved were initially new users of relational databases, there were some delays in achieving full adoption of a uniform approach to data handling. The software chosen was a commonly available desktop application which was modified using code developed to allow graphical queries, quality assurance of data, and interfacing with a purpose-built simulation model. A survey of users at the end of the project indicated that there was generally a high degree of satisfaction with the relational database developed, but it also identified areas requiring improvement. The need for developing mechanisms of sharing data and of protecting data for possible future use are briefly discussed.
Evaluation of the impact of SGS on livestock producers and their practices
Authors: Allan C. J. , Mason W. K. , Reeve I. J. , Hooper S.
Published: December 2005

The Sustainable Grazing Systems (SGS) Program has assisted producers in the high rainfall zone (HRZ, annual rainfall >600 mm/year) of southern Australia, by developing and delivering more productive and sustainable grazing systems. It was evaluated by 2 external surveys — a benchmarking survey in 1994 before the start of SGS, and a follow-up survey of producers in 2001. The 2001 survey showed that SGS had assisted red meat and wool producers in southern Australia make significant and beneficial changes to their grazing systems. Substantial changes in grazing practices occurred between 1994 and 2001 in the HRZ. These changes included an increase in the number of producers who rotationally graze (25%), as well as those undertaking practices aimed at improved pasture management. Participants in SGS were more likely to have made changes to their grazing systems than non-participants. There were no overt differences between regions in producer demographics, or changes made to management practices. The survey confirmed SGS had achieved its goal. Sixty percent of producers in the target regions were aware of SGS (out of a total of 23 689 producers); 42% (9839) had some involvement with SGS and/or received the SGS magazine 'Prograzier'; while 26% (6141) actively participated in SGS through undertaking a PROGRAZE course, and/or by attending regional SGS activities. Of the estimated 9839 producers who participated in the program, up to 8000 made beneficial changes to enhance the productivity and sustainability of their grazing operations. Active participants (6141) attributed many of these benefits to their involvement in SGS.
Mating Awassi rams to Merino ewes causes an initial level of fibre contamination which decreases to an insignificant level eight weeks post-mating
Authors: Hatcher S. , Hatcher S. , Lightfoot R. J. , Lightfoot R. J. , Purvis I. W. , Purvis I. W.
Published: December 2005

The fleeces of Merino ewes mated by Awassi rams
were analysed for the presence of contaminant fibres (pigmented, urine-stained
and kemp). In a controlled shed mating, high numbers of contaminant fibres
were found in the fleeces of the ewes, with the number of fibres transferred
being proportional to the number of times the ram mounted the ewe. The number
of fibres transferred during the shed mating were substantially higher than
those found after paddock mating. In the latter instance, environmental
conditions and contact with other sheep would have contributed to the loss of
fibres from the recipients’fleeces. Each ram breed used in the paddock
mating experiment, Merino, Awassi and Suffolk, transferred fibres into the
fleeces of the mated ewes. The Suffolk transferred relatively more fibres than
both the Awassi or the Merino rams, in addition the fibres from the Suffolk
were significantly darker than those from the other breeds thus compounding
the severity of the contamination. Both mating experiments demonstrated that
the number of contaminant fibres remaining in the ewe’s fleece 8 weeks
after mating was not different to that existing in the fleece of the ewes
before mating. Therefore, in commercial flocks, the risk of contamination can
be minimised by shearing breeding ewes 8 weeks after rams have been removed
from the breeding flocks.
Rhizobium strain evaluation of Glycine max cv. Davis, Vigna mungo cv. Regur and V. unguiculata cv. Caloona for three soils in glasshouse and field experiments
Authors: Bushby HVA , Date RA , Butler KL
Published: December 2005

The need for inoculation of soybean (Glycine max cv. Davis), gram (Vigna mungo cv. Regur) and cowpea (V. unguiculata cv. Caloona) with six appropriate strains of Rhizobium in two grain legume, clay soil growing areas (Narayen and Emerald, central Queensland) and a Rhizobium free (to sparse) soil (Beerwah, in south-eastern Queensland) was investigated in glasshouse and field experiments. Inoculated plants generally had vegetative and grain yields which were between those of the nitrogen and nil nitrogen uninoculated controls, although for the freely nodulating Vigna species the nil nitrogen control plants were sometimes as large as those in the inoculated treatments. The strains of Rhizobium CB1015 and CB1243 performed well on cowpea and gram as did most strains used as inoculum on soybean. Strain USDA94 was often poor on soybean. In the two heavy clay soils tested, plants inoculated with CB756 and the streptomycin-resistant mutant CB756str developed nitrogen deficiency symptoms in their leaves, suggesting that the strains were not suited to those soil types. There was not a close relationship between the glasshouse and field means due to large residual errors in the field.
Plant spacing in French beans. I. Yield
Authors: Daniells JW , Wilson GL
Published: December 2005

Four cultivars of French beans (Phaseolus vulgaris L.) were grown at a range of plant population densities and rectangularities in two seasons in south-eastern Queensland. Plant population densities two to three times those used commercially increased yields by 25-30%. This increase resulted from a greater number of pods per unit area with only a small reduction in pod size. Rectangularity in the range 1-8 had no effect on yield. These responses are discussed in terms of time courses of leaf area index development, light interception by canopies, crop growth rates and dry matter distribution between vegetative and reproductive growth after flowering.
Transformation and recovery of urea applied to a grass pasture in south-eastern Queensland
Authors: Catchpoole VR , Oxenham DJ , Harper LA
Published: December 2005

The fate of urea-N during the 14 d after four seasonal applications to a Setaria sphacelata cv. Nandi pasture in south-eastern Queensland was traced. The aim was to explain the variations in the responses by grass, which have been observed after applications of urea. The total losses of urea-15N from the soil-plant system and the fluxes of NH, into the atmosphere were respectively 29 and 12% of the urea-N applied in summer, 45 and 42% in autumn, 23 and 13% in winter, and 20 and 9% in spring. Losses of nitrogen by leaching were probably negligible as mineral-N derived from the fertilizer remained mostly in the 0-2 cm layer of soil. Hydrolysis of urea to NH4+-N was complete after 1 d in summer, 3 d in spring, 6 d in autumn and 7 d in winter. Losses of urea-N were influenced by the water content of the surface soil (0-0.5 cm) at the time of the application and by the subsequent pattern of rainfall. The loss was large when urea was applied to wet soil and rainfall during the next 7 d did not exceed 1 mm, as in autumn. Losses were much smaller when rain (5 mm or more) fell soon after the applications, as in spring and summer. In winter urea was applied to dry soil and fluxes of NH, continued at a moderate rate until rain fell on the sixth day. Losses of 15N were generally about double the losses of NH,. Work on this discrepancy is needed to fully understand the fate of urea-N broadcast onto pastures. Losses of NH, from urea broadcast onto pastures could be minimized in practice by making applications to dry soil just before rain is expected or before irrigation.
An analysis of the variation in wool production between commercial properties from a survey of a wheat-sheep shire in New South Wales
Authors: Denney GD , Ridings HI , Thornberry KJ
Published: December 2005

A survey of Merino breeding properties in the Weddin Shire of New South Wales was used to relate the variation in wool production among properties to physical and management factors. Clean wool production averaged 3.15 kg per sheep and showed little variation between the eastern, central and western portions of the shire. However, clean wool production per hectare was greatest in the eastern portion where rainfall, pasture improvement and stocking rate were highest. Overall, ewes produced 88% as much wool as the wethers but variation was great, with 23% of the properties surveyed producing more wool per sheep from their ewes. The difference in productivity for properties in the highest and lowest quartiles was 71% when ranked on clean wool production per sheep. The difference was 184% when ranked on clean wool production per hectare, and even though stocking rate more than doubled, individual productivity increased. Similar differences in quartile production were observed in each portion of the shire. Regression analysis was used to test the importance of 9 physical and 10 management factors as determinants of the variation in clean wool production between properties. Four factors (stocking rate, managerial assessment, sheep strain/bloodline and location within shire) accounted for 74% of the variance in wool production per hectare, but after adjusting for the time of shearing, only 16% of the variance in wool production per sheep was explained. In a more specific analysis of wool production of the properties' ewe flock, 42% of the variance was accounted for by the source of genetic material, stocking rate, pasture improvement, time of lambing, the proportion of Merino ewes and an assessment of managerial ability. Research workers considering on-farm experimentation in wool production should be aware that large productivity differences can occur between nearby properties. Therefore, treatments should be allocated to properties based on known wool production. Further, results obtained from either the ewe, wether or hogget flocks may have application to only that class of sheep because of the large differences in commercial management imposed on them.
Effect of plant spacing and nitrogenous fertiliser on the yield and plant conformation of Chinese cabbage (Brassica campestris ssp. pekinensis)
Authors: Hill TR
Published: December 2005

The effects of plant spacing and nitrogenous (N) fertiliser on the yield and plant conformation of Chinese cabbage were investigated for the michihili cultivar, Early Jade Pagoda, at Manjimup, Western Australia. The soil type was a sandy loam (7% gravel, pH 5.9) over clay at 60 cm. The experimental design included 4 plant spacings (25 by 25 cm, 30 by 30 cm, 35 by 35 cm, 40 by 40 em), and 6 rates of N fertiliser (0, 50, 100, 200, 300 and 400 kg N/ha). The highest marketable yields, 126.6 and 123.6 tha, were produced at the closest spacing, 25 by 25 cm, with N fertiliser rates of 200 and 300 kg/ha, respectively. Marketable yield for this spacing increased as N rate increased from 0 to 200 kg/ha, remained constant from 200 to 300 kg/ha and fell when the N rate was increased to 400 kg/ha. Soft rot damage was severe at the highest rate of N fertiliser and contributed to the reduced yield. The yield potential of Chinese cabbage was higher at close spacings than at the wider spacings. Plant height was not affected by any treatment, but plant width increased at the higher N fertiliser rates.
Brassica napus (L.) var. napus (Rapeseed, canola) cv. Yickadee
Authors: Wratten N , Mailer RJ
Published: December 2005

NO ABSTRACTS AVAILABLE
Effects of salinity on the germination and seedling characteristics of cowpea [Vigna unguiculata (L.) Walp.]
Authors: Troyo-Diéguez E. , Murillo-Amador B.
Published: December 2005

Cowpea
[Vigna unguiculata (L.) Walp.], a species with
wide adaptation in arid and semi-arid zones, is grown from green seeds and
pods, and is tolerant to salinity. It is a hardy species capable of developing
in soils of low fertility. In this study, the effects of different salinities
and different submersion times on the germination and weight of seeds of
cowpea treated previously were evaluated. The effect of irrigation with saline
solutions on seedling shoot length and dry weight, stem height and dry weight,
total dry weight, and leaf area was also studied. The results show that the
weight of pre-treated seeds decreases linearly when submersion times were
increased. Germination decreased quadratically when submersion times and
salinity increased. Seedling total dry weight, leaf area, shoot length and dry
weight, stem height and dry weight all decreased quadratically significantly
when salinity increased.
Development of a hemp (Cannabis sativa L.) simulation model 4. Model description and validation
Authors: Lisson S. N. , Mendham N. J. , Carberry P. S.
Published: December 2005

In studies assessing the prospects for a hemp
industry, as well as in longer term research activities, the use of a hemp
simulation model to complement the more traditional agronomic field trials
would offer a number of potential advantages. In addition to being cost and
labour intensive, field trials with hemp have political, social and security
implications. With these implications in mind, a simulation model that
captures the growth and development processes of hemp in response to
management, genotypic, soil and climate factors, has the potential to increase
research efficiency. The model could be used to assess the need, extent and
nature of field trials, to help interpret field trial results, and to
investigate temporal and spatial variability in selected crop responses.
This paper describes a hemp crop growth and development model (APSIM-Hemp) and
its validation against an independent dataset. The model was developed as a
crop module within the framework of the larger systems model, Agricultural
Production Systems sIMulator (APSIM), to extend the capability to encompass
the agricultural system in which hemp is grown. APSIM-Hemp incorporates
relationships developed in the previous papers in this series relating to pre-
and post-emergent phenology and leaf area production. Other parameters
relating to biomass partitioning, biomass production, water uptake and
nitrogen uptake were derived from separate field studies and selected
references.
APSIM-Hemp adequately predicted phenology, leaf area and biomass production
for the cultivar Kompolti at Forthside in north-western Tasmania, for a
dataset comprised of results from trials conducted over 3 seasons and
including treatments of sowing date, irrigation regime and plant density.
Although performing well against this independent dataset, the performance of
the model needs to be further validated over a range of other soil, climate
and management conditions in order to assess its broader predictive
capability. Notwithstanding these limitations, the sound basis of a model for
simulating the growth and development of hemp has been developed.
Fallow management, soil water, plant-available soil nitrogen and grain sorghum production in south west Queensland
Authors: Gibson G , Radford BJ , Nielsen RGH
Published: December 2005

The effects of tillage frequency (conventional, reduced and zero), primary tillage implement (disc, blade and chisel plough), stubble management (retention and removal), gypsum application, and paraplowing were examined with respect to soil water storage, soil nitrate accumulation, crop establishment, crop growth, grain yield and grain nitrogen content for 4 successive sorghum crops on a sodic, texture-contrast soil in south west Queensland. Retention of sorghum stubble (v. removal) produced an increase in mean yield of sorghum grain of 393 kg/ha, due to increased soil water extraction and increased water use efficiency by the following crop. The highest mean yield occurred after reduced blade tillage with stubble retained. Zero tillage with stubble removed gave the lowest mean grain yield. Zero tillage always had the lowest quantity of soil nitrate-nitrogen at sowing. In one fallow, increased aggressiveness of primary tillage (disc v. blade plough) increased the quantity of nitrate-nitrogen in the top 60 cm of soil at sowing. These effects on available soil nitrogen did not result in corresponding differences in grain nitrogen content. Results indicate that for optimum fallow management on this texture-contrast soil in south west Queensland, sorghum residues should be retained, tillage frequency should be reduced, but not to zero, blade ploughing should be preferred to discing, and gypsum application should not be practised.
Virus indexing in the New South Wales citrus improvement scheme
Authors: Broadbent P , Dephoff CM
Published: December 2005

A virus indexing program was initiated in the 1950s to test local citrus clones with commercial potential, for the presence of citrus exocortis viroid and psorosis. As indexing techniques improved, clones have also been tested for the presence of citrus cachexia viroid and other viroids, citrus infectious variegation virus, citrus tatter leaf virus, and strain severity of citrus tristeza virus. Of 123 candidate clones tested, only 2 were infected with psorosis virus. Crinkly leaf (infectious variegation virus) was widespread in lemons but has been eliminated by nucellar embryony. The widespread incidence of citrus exocortis and other lower molecular weight viroids has been reduced by screening mother trees on Poncirus trifoliata stocks, biological indexing, and, more recently, by sequential polyacrylamide gel electrophoresis of RNA extracts. Cachexia is rarely found in Australian citrus clones.
Potassium nutrition of Kennebec and Russet Burbank potatoes in Tasmania: effect of soil and fertiliser potassium on yield, petiole and tuber potassium concentrations, and tuber quality
Authors: Chapman KSR , Sparrow LA , Hardman PR , Wright DN , Thorp JRA
Published: December 2005

The response of potato (Solanum tuberosum L.) cultivars Russet Burbank and Kennebec to soil and fertiliser potassium (K) was studied on basaltic krasnozems of north-west Tasmania. Yield increases in response to fertiliser K were recorded at sites with up to 300-400 mg/kg of bicarbonate extractable soil K. The close correlation between relative yield and soil K indicated that soil K can reliably predict fertiliser requirements. Petiole K concentrations at early tuber set increased with fertiliser K at responsive sites; maximum yields were achieved with 12-14% petiole K for Kennebec and 11-13% for Russet Burbank. Petiole K concentrations provide an excellent indication of the K status of a growing crop. Tuber K concentrations increased with both soil and fertiliser K, and yields of 50-80 t/ha removed 180-380 kg K/ha in the tubers. At severely deficient sites specific gravity and crisp colour increased with low rates of fertiliser K, but the general trend was for fertiliser K to reduce specific gravity and crisp colour. Bruising susceptibility decreased with fertiliser K at some sites but the physiological disorder, 'hollow heart', was not influenced by fertiliser K. There were consistent differences between the 2 cultivars. Russet Burbank required higher soil K, had lower petiole and tuber K concentrations and removed less K in the marketable tubers.
Internalization and phagosome escape required forFrancisellato induce human monocyte IL-1β processing and release
Authors: Gavrilin Mikhail A. , Bouakl Imad J. , Knatz Nina L. , Duncan Michelle D. , Hall Mark W. , Gunn John S. , Wewers Mark D.
Published: December 2005

Macrophage responses toFrancisellainfection have been characterized previously by subdued proinflammatory responses; however, these studies have generally focused on macrophage cell lines or monocyte-derived macrophages. Therefore, we studied the ability of fresh human blood monocytes to engulf and respond toFrancisellaby using the live vaccine strain variant andFrancisella novicida. BecauseFrancisellaorganisms have been reported to escape from the phagolysosome into the cytosol, we hypothesized that this escape may trigger the activation of caspase-1.Francisella tularensisvariants were readily taken up by fresh human CD14+monocytes, inducing the release of IL-1β, as well as IL-8, in a time- and dose-dependent fashion. Importantly, whereas live and deadEscherichia coli,F. novicida, and live vaccine strain, as well as the LPS ofE. coli, were able to induce abundant IL-1β mRNA synthesis and intracellular pro-IL-1β production, only liveFrancisellainduced enhanced IL-1β processing and release (51 ± 10 vs. 7.1 ± 2.1 ng/ml, forF. novicidavs.E. coliLPS;P= 0.0032). Cytochalasin D blocked theFrancisellainternalization and theFrancisella-induced monocyte IL-1β processing and release but not that induced by the exogenous stimulusE. coliLPS. Also, killing bacteria did not block uptake but significantly diminished the IL-1β processing and release that was induced byFrancisella. Blocking bacterial escape from the phagosome into the cytosol also decreased IL-1β but not IL-8 release. These findings demonstrate thatFrancisellaorganisms efficiently induce IL-1β processing and release in fresh monocytes by means of a sensing system that requires the uptake of live bacteria capable of phagosome escape.
Silent plateau potentials, rhythmic bursts, and pacemaker firing: Three patterns of activity that coexist in quadristable subthalamic neurons
Authors: Kass Jason I. , Mintz Isabelle M.
Published: December 2005

Subthalamic neurons display uncommon intrinsic behaviors that are likely to contribute to the motor and cognitive functions of the basal ganglia and to many of its disorders. Here, we report silent plateau potentials in these cells. These plateau responses start with a transient burst of action potentials that quickly diminish in amplitude because of spike inactivation and current shunt. The resulting interruption of spiking reveals a stable depolarization (up state) that clamps the cell membrane potential near –40 mV for several seconds. These plateau potentials coexist in single subthalamic neurons with more familiar patterns of burst and pacemaker firing. Within a narrow range of baseline membrane potentials (–67 to –60 mV), depolarization abruptly switches single cells from bistable to rhythmic bursts or tonic firing modes, thus selecting entirely distinct algorithms for integrating cortical and pallidal synaptic inputs.
Specific, efficient, and selective inhibition of prokaryotic translation initiation by a novel peptide antibiotic
Authors: Brandi Letizia , Fabbretti Attilio , La Teana Anna , Abbondi Monica , Losi Daniele , Donadio Stefano , Gualerzi Claudio O.
Published: December 2005

Many known antibiotics target the translational apparatus, but none of them can selectively inhibit initiation of protein synthesis and/or is prokaryotic-specific. This article describes the properties of GE81112, an effective and prokaryotic-specific initiation inhibitor. GE81112 is a natural tetrapeptide produced by a
Streptomyces
sp. identified by an
in vitro
high-throughput screening test developed to find inhibitors of the prokaryotic translational apparatus preferentially acting on steps other than elongation.
In vivo
GE81112 inhibits protein synthesis but not other cell functions such as DNA duplication, transcription, and cell wall synthesis.
In vitro
GE81112 was found to target the 30S ribosomal subunit and to interfere with both coded and noncoded P-site binding of fMet-tRNA, thereby selectively inhibiting formation of the 30S initiation complex.
Mouse model for noninvasive imaging of HIF prolyl hydroxylase activity: Assessment of an oral agent that stimulates erythropoietin production
Authors: Safran Michal , Kim William Y. , O'Connell Fionnuala , Flippin Lee , Günzler Volkmar , Horner James W. , DePinho Ronald A. , Kaelin William G.
Published: December 2005

Many human diseases are characterized by the development of tissue hypoxia. Inadequate oxygenation can cause cellular dysfunction and death. Tissues use many strategies, including induction of angiogenesis and alterations in metabolism, to survive under hypoxic conditions. The heterodimeric transcription factor hypoxia-inducible factor (HIF) is a master regulator of genes that promote adaptation to hypoxia. HIF activity is linked to oxygen availability because members of the EGLN family hydroxylate HIFα subunits on specific prolyl residues when oxygen is present, which marks them for ubiquitination and proteasomal degradation. We created a mouse that ubiquitously expresses a bioluminescent reporter consisting of firefly luciferase fused to a region of HIF that is sufficient for oxygen-dependent degradation. Our validation studies suggest that this mouse will be useful for monitoring hypoxic tissues and evaluating therapeutic agents that stabilize HIF. One such agent, the HIF prolyl hydroxylase inhibitor FG-4383, was active in the liver and kidney after systemic administration as determined by bioluminescence imaging, transcription profiling, and production of erythropoietin, indicating that the HIF transcriptional program can be manipulatedin vivowith orally active organic small molecules.
Atherosclerosis quantitative trait loci are sex- and lineage-dependent in an intercross of C57BL/6 and FVB/N low-density lipoprotein receptor
–/–
mice
Authors: Teupser Daniel , Tan Marietta , Persky Adam D. , Breslow Jan L.
Published: December 2005

Atherosclerosis is a complex disease that is affected by environmental as well as genetic factors. The aim of the present study was to identify loci of atherosclerosis susceptibility in a cross of atherosclerosis-susceptible C57BL/6 and atherosclerosis-resistant FVB/N mice on the low-density lipoprotein (LDL) receptor (LDLR)-deficient background (LDLR
–/–
) and to test whether these loci are affected by lineage. A total of 459 F
2
s were generated in two ways: In cross “mB6xfFVB,” male B6.LDLR
–/–
mice were crossed to female FVB.LDLR
–/–
mice to generate 107 female and 112 male F
2
s. In cross “mFVBxfB6,” male FVB.LDLR
–/–
mice were crossed to female B6.LDLR
–/–
mice to generate 120 female and 120 male F
2
s. Animals were phenotyped for cross-sectional atherosclerotic lesion area at the aortic root, and a genome scan was carried out with 192 microsatellite markers. Quantitative trait locus mapping revealed significant loci of atherosclerosis susceptibility on chromosomes 3, 10, and 12. On chromosome 10 maximal logarithm of odds (LOD) scores of 13.1 (
D10Mit16
, 16 cM) and 5.7 (
D10Mit168
, 9 cM) were found in female and male mice, respectively. On chromosome 3, a maximal LOD score of 5.1 (
D3Mit45
, 79 cM) was detected only in females. On proximal chromosome 12 significant LOD scores were lineage-dependent, with maximal LOD scores of 3.9 (
D12Mit82
, 3 cM) and 4.8 (
D12Mit189
, 24 cM) present only in female mice of cross mB6xfFVB and male mice of cross mFVBxfB6, respectively. We conclude that, in this intercross, loci of atherosclerosis susceptibility are in part sex- and lineage-dependent. Awareness of these complexities may have major consequences for the identification of atherosclerosis susceptibility genes by quantitative trait locus mapping.
Mapping of orthologous genes in the context of biological pathways: An application of integer programming
Authors: Mao Fenglou , Su Zhengchang , Olman Victor , Dam Phuongan , Liu Zhijie , Xu Ying
Published: December 2005

Mapping biological pathways across microbial genomes is a highly important technique in functional studies of biological systems. Existing methods mainly rely on sequence-based orthologous gene mapping, which often leads to suboptimal mapping results because sequence-similarity information alone does not contain sufficient information for accurate identification of orthology relationship. Here we present an algorithm for pathway mapping across microbial genomes. The algorithm takes into account both sequence similarity and genomic structure information such as operons and regulons. One basic premise of our approach is that a microbial pathway could generally be decomposed into a few operons or regulons. We formulated the pathway-mapping problem to map genes across genomes to maximize their sequence similarity under the constraint that the mapped genes be grouped into a few operons, preferably coregulated in the target genome. We have developed an integer-programming algorithm for solving this constrained optimization problem and implemented the algorithm as a computer software program,
p
-
map
. We have tested
p
-
map
on a number of known homologous pathways. We conclude that using genomic structure information as constraints could greatly improve the pathway-mapping accuracy over methods that use sequence-similarity information alone.
Inositols prevent and reverse endothelial dysfunction in diabetic rat and rabbit vasculature metabolically and by scavenging superoxide
Authors: Nascimento N. R. F. , Lessa L. M. A. , Kerntopf M. R. , Sousa C. M. , Alves R. S. , Queiroz M. G. R. , Price J. , Heimark D. B. , Larner J. , Du X. , Brownlee M. , Gow A. , Davis C. , Fonteles M. C.
Published: December 2005

Endothelial dysfunction (ED) is an early feature of cardiovascular risk and diabetes. Hyperglycemia and hyperlipidemia are causative factors. Excessive endothelial mitochondrial superoxide (ROS) production with hyperglycemia and hyperlipidemia is a key mechanism. Inositol components of an insulin inositol glycan mediator,d-chiro-inositol (DCI) and 3-O-methyl DCI (pinitol), decrease hyperglycemia and hyperlipidemia. We tested whether these, myoinositol and dibutyryl DCI (db-DCI), would prevent or reverse ED in diabetic rats and rabbits. Oral inositols reduced hyperglycemia and hypertriglyceridemia with different potencies and prevented ED in rat aortic rings and mesenteric beds. Inositols addedin vitroto five diabetic tissues reversed ED. Relaxation by Ach, NO, and electrical field stimulation was potentiated by inositolsin vitroin rabbit penile corpus cavernosa. Inositolsin vitrorestored impaired contraction by the eNOS inhibitorl-NAME and increased NO effectiveness. DCI and db-DCI decreased elevated ROS in endothelial cells in high glucose and db-DCI reduced PKC activation, hexosamine pathway activity, and advanced glycation end products to basal levels. Xanthine/xanthine oxidase generated superoxide was reduced by superoxide dismutase or inositols, with db-DCI efficacious in a mechanism requiring chelated Fe3+. Histochemical examination of rat aortic rings for protein SNO demonstrated a decrease in diabetic rings with restoration by inositols. In summary, inositols prevented and reversed ED in rat and rabbit vessels, reduced elevated ROS in endothelial cells, potentiated nitrergic or vasculo-myogenic relaxations, and preserved NO signaling. These effects are related to their metabolic actions, direct superoxide scavenging, and enhancing and protecting NO signaling. Of the inositols tested, db-DCI was most effective.
Cinnamoyl-CoA reductase, a key enzyme in lignin biosynthesis, is an effector of small GTPase Rac in defense signaling in rice
Authors: Kawasaki Tsutomu , Koita Hisako , Nakatsubo Tomoyuki , Hasegawa Kana , Wakabayashi Kenichi , Takahashi Hiroki , Umemura Kenji , Umezawa Toshiaki , Shimamoto Ko
Published: December 2005

OsRac1, one of the Rac/Rop family of small GTPases, plays important roles in defense responses, including a role in the production of reactive oxygen species mediated by NADPH oxidase. We have identified an effector of OsRac1, namely rice (
Oryza sativa
) cinnamoyl-CoA reductase 1 (OsCCR1), an enzyme involved in lignin biosynthesis. Lignin, which is polymerized through peroxidase activity by using H
2
O
2
in the cell wall, is an important factor in plant defense responses, because it presents an undegradable mechanical barrier to most pathogens. Expression of
OsCCR1
was induced by a sphingolipid elicitor, suggesting that
OsCCR1
participates in defense signaling. In
in vitro
interaction and two-hybrid experiments, OsRac1 was shown to bind OsCCR1 in a GTP-dependent manner. Moreover, the interaction of OsCCR1 with OsRac1 led to the enzymatic activation of OsCCR1
in vitro
. Transgenic cell cultures expressing the constitutively active OsRac1 accumulated lignin through enhanced CCR activity and increased reactive oxygen species production. Thus, it is likely that OsRac1 controls lignin synthesis through regulation of both NADPH oxidase and OsCCR1 activities during defense responses in rice.
PTEN negatively regulates neural stem cell self-renewal by modulating G0-G1cell cycle entry
Authors: Groszer Matthias , Erickson Rebecca , Scripture-Adams Deirdre D. , Dougherty Joseph D. , Le Belle Janel , Zack Jerome A. , Geschwind Daniel H. , Liu Xin , Kornblum Harley I. , Wu Hong
Published: December 2005

Previous studies have demonstrated that a small subpopulation of brain tumor cells share key characteristics with neural stem/progenitor cells in terms of phenotype and behavior. These findings suggest that brain tumors might contain “cancer stem cells” that are critical for tumor growth. However, the molecular pathways governing such stem cell-like behavior remain largely elusive. Our previous study suggests that the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor gene, one of the most frequently mutated genes in glioblastomas, restricts neural stem/progenitor cell proliferationin vivo. In the present study, we sought to determine the role of PTEN in long-term maintenance of stem cell-like properties, cell cycle entry and progression, and growth factor dependence and gene expression. Our results demonstrate an enhanced self-renewal capacity and G0-G1cell cycle entry and decreased growth factor dependency ofPtennull neural/stem progenitor cells. Therefore, loss of PTEN leads to cell physiological changes, which collectively are sufficient to increase the pool of self-renewing neural stem cells and promote their escape from the homeostatic mechanisms of proliferation control.
A Mixture of Ammonium Perchlorate and Sodium Chlorate Enhances Alterations of the Pitutary-Thyroid Axis Caused by the Individual Chemicals in Adult Male F344 Rats
Authors: Khan Moazzam A. , Fenton Suzanne E. , Swank Adam E. , Hester Susan D. , Williams A. , Wolf Douglas C.
Published: December 2005

Ammonium perchlorate (AP) and sodium chlorate (SC) have been detected in public drinking water supplies in many parts of the United States. These chemicals cause perturbations in pituitary-thyroid homeostasis in animals by competitively inhibiting iodide uptake, thus hindering the synthesis of thyroglobulin and reducing circulating T4(thyroxine). Little is known about the short-term exposure effects of mixtures of perchlorate and chlorate. The present study investigated the potential for the response to a mixture of these chemicals on the pituitary-thyroid axis in rats to be greater than that induced by the individual chemicals. Adult male F-344 rats were exposed, via their drinking water, to the nominal concentrations of 0.1, 1.0, 10 mg/L AP or 10, 100, 1000 mg/L SC and their mixtures for 7 days. Serum T4levels were significantly ( p < 0.05) reduced in rats following exposure to the mixtures, but not after exposure to the individual chemicals. Serum T3(triiodothyronine) was not altered by treatment and TSH (thyroid stimulating hormone) was only increased after the high-dose chlorate treatment. Histological examination of the thyroid gland showed colloid depletion and hypertrophy of follicular epithelial cells in high-dose single chemical and all mixture-treated rats, while hyperplasia was observed only in some of the rats treated with mixtures (AP 10 + SC 100, AP 0.1 + SC 1000, and AP 10 + SC 1000 mg/L). These data suggest that short-term exposure to the mixture of AP and SC enhances the effect of either chemical alone on the pituitary-thyroid axis in rats.
Immunohistochemical Analysis of Acetylation, Proliferation, Mitosis, and Apoptosis in Tumor Xenografts Following Administration of a Histone Deacetylase Inhibitor—A Pilot Study
Authors: Mitiæ Tijana , McKay Jennifer S.
Published: December 2005

Histone acetyltransferases and histone deacetylases are protein-modifying enzymes involved in addition and removal of acetyl groups on histone proteins, respectively. These molecules play a pivotal role in cellular functions such as chromosome remodelling, gene transcription and cell proliferation. Histone deacetylase inhibitors (HDIs) have been shown to cause cell cycle arrest, cellular differentiation and inhibition of cell proliferation in tumor cells in vitro and in vivo. Their potential use for cancer therapy is currently under evaluation in clinical trials. A pilot study was performed to immunohistochemically evaluate the effects of a HDI, “Compound 1,” on acetylation, proliferation, mitosis, and apoptosis in tumor xenografts (Calu-6, SW 620, Colo 205, and LoVo) in nude mice, at 6, 24, and 48 hours, following a single oral dose. Qualitative immunohistochemistry and computer-assisted image analysis demonstrated an increase in acetylation in all xenografts. Immunohistochemical analysis of acetylation in skin showed increased acetylation at 6 hours after HDI administration. In addition, image analysis showed a decrease in mitosis and an increase in metaphase mitotic figures in the SW 620 xenograft. These two findings were consistent with a G1/S cell cycle phase arrest. Increased apoptosis of SW 620 and LoVo xenografts was also observed following treatment.
Pax3 and Pax7 have distinct and overlapping functions in adult muscle progenitor cells
Authors: Relaix Frédéric , Montarras Didier , Zaffran Stéphane , Gayraud-Morel Barbara , Rocancourt Didier , Tajbakhsh Shahragim , Mansouri Ahmed , Cumano Ana , Buckingham Margaret
Published: December 2005

The growth and repair of skeletal muscle after birth depends on satellite cells that are characterized by the expression of Pax7. We show that Pax3, the paralogue of Pax7, is also present in both quiescent and activated satellite cells in many skeletal muscles. Dominant-negative forms of both Pax3 and -7 repress MyoD, but do not interfere with the expression of the other myogenic determination factor, Myf5, which, together with Pax3/7, regulates the myogenic differentiation of these cells. In Pax7 mutants, satellite cells are progressively lost in both Pax3-expressing and -nonexpressing muscles. We show that this is caused by satellite cell death, with effects on the cell cycle. Manipulation of the dominant-negative forms of these factors in satellite cell cultures demonstrates that Pax3 cannot replace the antiapoptotic function of Pax7. These findings underline the importance of cell survival in controlling the stem cell populations of adult tissues and demonstrate a role for upstream factors in this context.
Coupling of the nucleus and cytoplasm: Role of the LINC complex
Authors: Crisp Melissa , Liu Qian , Roux Kyle , Rattner J.B. , Shanahan Catherine , Burke Brian , Stahl Phillip D. , Hodzic Didier
Published: December 2005

The nuclear envelope defines the barrier between the nucleus and cytoplasm and features inner and outer membranes separated by a perinuclear space (PNS). The inner nuclear membrane contains specific integral proteins that include Sun1 and Sun2. Although the outer nuclear membrane (ONM) is continuous with the endoplasmic reticulum, it is nevertheless enriched in several integral membrane proteins, including nesprin 2 Giant (nesp2G), an 800-kD protein featuring an NH2-terminal actin-binding domain. A recent study (Padmakumar, V.C., T. Libotte, W. Lu, H. Zaim, S. Abraham, A.A. Noegel, J. Gotzmann, R. Foisner, and I. Karakesisoglou. 2005. J. Cell Sci. 118:3419–3430) has shown that localization of nesp2G to the ONM is dependent upon an interaction with Sun1. In this study, we confirm and extend these results by demonstrating that both Sun1 and Sun2 contribute to nesp2G localization. Codepletion of both of these proteins in HeLa cells leads to the loss of ONM-associated nesp2G, as does overexpression of the Sun1 lumenal domain. Both treatments result in the expansion of the PNS. These data, together with those of Padmakumar et al. (2005), support a model in which Sun proteins tether nesprins in the ONM via interactions spanning the PNS. In this way, Sun proteins and nesprins form a complex that links the nucleoskeleton and cytoskeleton (the LINC complex).
Histone deacetylase 2–mediated deacetylation of the glucocorticoid receptor enables NF-κB suppression
Authors: Ito Kazuhiro , Yamamura Satoshi , Essilfie-Quaye Sarah , Cosio Borja , Ito Misako , Barnes Peter J. , Adcock Ian M.
Published: December 2005

Glucocorticoids are the most effective antiinflammatory agents for the treatment of chronic inflammatory diseases even though some diseases, such as chronic obstructive pulmonary disease (COPD), are relatively glucocorticoid insensitive. However, the molecular mechanism of this glucocorticoid insensitivity remains uncertain. We show that a defect of glucocorticoid receptor (GR) deacetylation caused by impaired histone deacetylase (HDAC) 2 induces glucocorticoid insensitivity toward nuclear factor (NF)-κB–mediated gene expression. Specific knockdown of HDAC2 by RNA interference resulted in reduced sensitivity to dexamethasone suppression of interleukin 1β–induced granulocyte/macrophage colony-stimulating factor production. Loss of HDAC2 did not reduce GR nuclear translocation, GR binding to glucocorticoid response element (GRE) on DNA, or GR-induced DNA or gene induction but inhibited the association between GR and NF-κB. GR becomes acetylated after ligand binding, and HDAC2-mediated GR deacetylation enables GR binding to the NF-κB complex. Site-directed mutagenesis of K494 and K495 reduced GR acetylation, and the ability to repress NF-κB–dependent gene expression becomes insensitive to histone deacetylase inhibition. In conclusion, we show that overexpression of HDAC2 in glucocorticoid-insensitive alveolar macrophages from patients with COPD is able to restore glucocorticoid sensitivity. Thus, reduction of HDAC2 plays a critical role in glucocorticoid insensitivity in repressing NF-κB–mediated, but not GRE-mediated, gene expression.
An essential role for complement C5a in the pathogenesis of septic cardiac dysfunction
Authors: Niederbichler Andreas D. , Hoesel Laszlo M. , Westfall Margaret V. , Gao Hongwei , Ipaktchi Kyros R. , Sun Lei , Zetoune Firas S. , Su Grace L. , Arbabi Saman , Sarma J. Vidya , Wang Stewart C. , Hemmila Mark R. , Ward Peter A.
Published: December 2005

Defective cardiac function during sepsis has been referred to as “cardiomyopathy of sepsis.” It is known that sepsis leads to intensive activation of the complement system. In the current study, cardiac function and cardiomyocyte contractility have been evaluated in rats after cecal ligation and puncture (CLP). Significant reductions in left ventricular pressures occurred in vivo and in cardiomyocyte contractility in vitro. These defects were prevented in CLP rats given blocking antibody to C5a. Both mRNA and protein for the C5a receptor (C5aR) were constitutively expressed on cardiomyocytes; both increased as a function of time after CLP. In vitro addition of recombinant rat C5a induced dramatic contractile dysfunction in both sham and CLP cardiomyocytes, but to a consistently greater degree in cells from CLP animals. These data suggest that CLP induces C5aR on cardiomyocytes and that in vivo generation of C5a causes C5a–C5aR interaction, causing dysfunction of cardiomyocytes, resulting in compromise of cardiac performance.
Purified hematopoietic stem cell engraftment of rare niches corrects severe lymphoid deficiencies without host conditioning
Authors: Bhattacharya Deepta , Rossi Derrick J. , Bryder David , Weissman Irving L.
Published: December 2005

In the absence of irradiation or other cytoreductive conditioning, endogenous hematopoietic stem cells (HSCs) are thought to fill the unique niches within the bone marrow that allow maintenance of full hematopoietic potential and thus prevent productive engraftment of transplanted donor HSCs. By transplantation of purified exogenous HSCs into unconditioned congenic histocompatible strains of mice, we show that ∼0.1–1.0% of these HSC niches are available for engraftment at any given point and find no evidence that endogenous HSCs can be displaced from the niches they occupy. We demonstrate that productive engraftment of HSCs within these empty niches is inhibited by host CD4+ T cells that recognize very subtle minor histocompatibility differences. Strikingly, transplantation of purified HSCs into a panel of severe combined immunodeficient (SCID) mice leads to a rapid and complete rescue of lymphoid deficiencies through engraftment of these very rare niches and expansion of donor lymphoid progenitors. We further demonstrate that transient antibody-mediated depletion of CD4+ T cells allows short-term HSC engraftment and regeneration of B cells in a mouse model of B(-) non-SCID. These experiments provide a general mechanism by which transplanted HSCs can correct hematopoietic deficiencies without any host conditioning or with only highly specific and transient lymphoablation.
Dual specificity phosphatase 1 (DUSP1) regulates a subset of LPS-induced genes and protects mice from lethal endotoxin shock
Authors: Hammer Michael , Mages Jörg , Dietrich Harald , Servatius Angela , Howells Norma , Cato Andrew C.B. , Lang Roland
Published: December 2005

Activation of the mitogen-activated protein kinase (MAPK) cascade after Toll-like receptor stimulation enables innate immune cells to rapidly activate cytokine gene expression. A balanced response to signals of infectious danger requires that cellular activation is transient. Here, we identify the MAPK phosphatase dual specificity phosphatase 1 (DUSP1) as an essential endogenous regulator of the inflammatory response to lipopolysaccharide (LPS). DUSP1-deficient (DUSP1−/−) bone marrow–derived macrophages showed selectively prolonged activation of p38 MAPK and increased cytokine production. Intraperitoneal challenge of DUSP1−/− mice with LPS caused increased lethality and overshooting production of interleukin (IL)-6 and tumor necrosis factor α. Transcriptional profiling revealed that DUSP1 controls a significant fraction of LPS-induced genes, which includes IL-6 and IL-10 as well as the chemokines CCL3, CCL4, and CXCL2. In contrast, the expression of the important mediators of endotoxin lethality, interferon γ and IL-12, was not significantly altered by the absence of DUSP1. These data together demonstrate a specific regulatory role of DUSP1 in controlling a subset of LPS-induced genes that determines the outcome of endotoxin shock.