bluuebunny/crossref_metadata_2025 huggingface dataset:
Are migraineurs hypersensitive? A test of the stimulus processing disorder hypothesis
Authors: Kröner‐Herwig Birgit , Ruhmland Martina , Zintel Wolfgang , Siniatchkin Michael
Published: January 2005

The concept of hypersensitivity in migraineurs was advanced mainly on the basis of studies on information processing in which increased amplitudes and reduced habituation in cortical evoked and event related potentials were found in migraine sufferers.

The present investigation examined whether migraineurs exhibit hypersensitivity within three different experimental paradigms and various non electrocortical response parameters. Samples of 24 migraine, 19 tension‐type headache sufferers, and 24 normal controls were compared regarding their subjective estimation of intensity and discomfort due to visual and acoustical stimuli. Subjects also participated in an experiment using the eyeblink startle response paradigm. In a last experimental task the Stroop test was applied. The trait variables emotionality, arousal, and extraversion were also measured.

None of the experimental tasks revealed the predicted hypersensitivity of migraineurs in relation to the control samples. The series of experiments was conducted a second time with half of the participants in order to replicate the findings. The conclusions remained the same.

The results of earlier studies on cortical processing can not be interpreted as demonstrating general hypersensitivity in the sense of a dispositional trait in migraine afflicted individuals irrespective of the involved response system.
Long-term follow-up after severe suicide attempt by multiple blunt trauma
Authors: Pajonk Frank-Gerald , Ruchholtz Steffen , Waydhas Christian , Schneider-Axmann Thomas
Published: January 2005

Background

After parasuicide there is a high risk of reattempts. However, it seems that patients who survived severe suicidal trauma recover well. Therefore, the outcome of patients with severe multiple blunt trauma as a result of a suicide attempt was investigated with respect to psychiatric and somatic health, quality of life (QOL) and suicide reattempt rates.

Methods

Patients who underwent a suicide attempt were isolated from a prospectively collected sample of trauma patients from a level I University Trauma Centre. Follow-up examination was performed 6.1 ± 3 years after the trauma. A physical and psychiatric examination was performed, using established psychiatric scales.

Results

Twelve percent of severely injured patients were identified as suicide attempters (male/female: 37/28, mean age 38 ± 18 years, mean Injury Severity Score (ISS) 40 ± 15 points). A psychiatric diagnosis was present in 90% at the time of the suicide attempt. Twenty-one patients died during the hospital stay (32%) and six subjects died thereafter, none due to suicide. Thirty-five individuals were eligible for examination. None of them had reattempted suicide. Seventeen (48%) had good outcomes reflected by absent or ambulatory psychiatric treatment, employment, normal psychiatric findings and good psychosocial ability. An indeterminate outcome was determined in 24%. Predictive variables for an adverse outcome (10 patients, 28%) were found to be a diagnosis of schizophrenia, continued psychiatric treatment and being without employment.

Conclusions

Despite the seriousness of the suicide attempt, survivors recovered well in about half the cases with no further suicide attempt in any patient. An early psychiatric consultation already on the Intensive Care Unit (ICU) is recommended.
Mutational analysis of the role of calcium ions in the Lactobacillus reuteri strain 121 fructosyltransferase (levansucrase and inulosucrase) enzymes
Authors: Ozimek L.K. , Euverink G.J.W. , van der Maarel M.J.E.C. , Dijkhuizen L.
Published: January 2005

Bacterial fructosyltransferase enzymes belonging to glycoside hydrolase family 68 (GH68) are not known to require a metal cofactor. Here, we show that Ca2+ ions play an important structural role in the Lactobacillus reuteri 121 levansucrase (Lev) and inulosucrase (Inu) enzymes. Analysis of the Bacillus subtilis Lev 3D structure [Meng, G. and Futterer, K. (2003) Nat. Struct. Biol. 10, 935–941] has provided evidence for the presence of a bound metal ion, most likely Ca2+. Characterization of site‐directed mutants in the putative Ca2+ ion‐binding sites of Lb. reuteri Lev and Inu revealed that the Inu Asp520 and Lev Asp500 residues play an important role in Ca2+ binding. Sequence alignments of family GH68 proteins showed that this Ca2+ ion‐binding site is (largely) present only in proteins of Gram‐positive origin.
An alternatively‐spliced exon in the 5′‐UTR of human ALAS1 mRNA inhibits translation and renders it resistant to haem‐mediated decay
Authors: Roberts Andrew G. , Redding Sadie J. , Llewellyn David H.
Published: January 2005

Haem controls its own synthesis in non‐erythroid cells primarily by regulation of ALAS1 mRNA stability. Alternative splicing of human ALAS1 generates two mRNAs with different 5′‐UTRs: a major one, where exon 1B is omitted, and a minor form containing exon 1B. We show that, unlike the major ALAS1 mRNA, the minor form was resistant to haem‐mediated decay. Furthermore, we demonstrate that the ALAS1 5′‐UTR alone did not confer haem‐mediated decay upon a heterologous mRNA and the inclusion of exon 1B inhibited translation. These data suggest that translation of ALAS1 mRNA itself might be required for destabilisation in response to haem.
α7B Integrin changes in mdx mouse muscles after l‐arginine administration
Authors: Chazalette Delphine , Hnia Karim , Rivier François , Hugon Gérald , Mornet Dominique
Published: January 2005

Muscle fibers attach to laminin in the basal lamina using two mechanisms, i.e., dystrophin with its associated proteins and α7β1 integrin. In humans, gene‐mutation defects in one member of these complexes result in muscular dystrophies. This study revealed changes after l‐arginine treatment of utrophin‐associated proteins and the α7B integrin subunit in mdx mouse, a dystrophin‐deficient animal model. In the two studied muscles (cardiac muscle and diaphragm), the α7B integrin subunit was increased in 5‐week‐old treated mice. Interestingly, the diaphragm histopathological appearance was significantly improved by l‐arginine administration. These results highlight a possible way to compensate for dystrophin deficiency via α7β1 integrin.
Unique genetic compartmentalization of the SUF system in cryptophytes and characterization of a SufD mutant in Arabidopsis thaliana
Authors: Hjorth Elmar , Hadfi Katalin , Zauner Stefan , Maier Uwe-G.
Published: January 2005

The mobilization of sulfur (SUF) system is one of three systems involved in iron–sulfur cluster biosynthesis and maintenance. In eukaryotes the SUF system is specific for the plastid and therefore of symbiotic origin. Analyses in cryptophytes showed a unique genetic compartmentalization of the SUF system, which evolved by at least two different gene transfer events. We analyzed one of the components, SufD, in the cryptophyte Guillardia theta and in Arabidopsis thaliana. We demonstrated that SufD fulfils house keeping functions during embryogenesis and in adult plants in A. thaliana.
Neutron diffraction reveals sequence‐specific membrane insertion of pre‐fibrillar islet amyloid polypeptide and inhibition by rifampicin
Authors: Balali-Mood Kia , Ashley Richard H. , Hauß Thomas , Bradshaw Jeremy P.
Published: January 2005

Human islet amyloid polypeptide (hIAPP) forms amyloid deposits in non‐insulin‐dependent diabetes mellitus (NIDDM). Pre‐fibrillar hIAPP oligomers (in contrast to monomeric IAPP or mature fibrils) increase membrane permeability, suggesting an important role in the disease. In the first structural study of membrane‐associated hIAPP, lamellar neutron diffraction shows that oligomeric hIAPP inserts into phospholipid bilayers, and extends across the membrane. Rifampicin, which inhibits hIAPP‐induced membrane permeabilisation in functional studies, prevents membrane insertion. In contrast, rat IAPP (84% identical to hIAPP, but non‐amyloidogenic) does not insert into bilayers. Our findings are consistent with the hypothesis that membrane‐active pre‐fibrillar hIAPP oligomers insert into beta cell membranes in NIDDM.
SorCS3 does not require propeptide cleavage to bind nerve growth factor
Authors: Westergaard U.B. , Kirkegaard K. , Sørensen E.S. , Jacobsen C. , Nielsen M.S. , Petersen C.M. , Madsen P.
Published: January 2005

The functional properties of the Vps10p‐domain receptor SorCS3 are undescribed. Here, we examine its processing and sorting in cellular transfectants, and analyze the binding of potential ligands to the purified receptor. We show that SorCS3 is synthesized as a proprotein and converted to its mature form by N‐terminal propeptide cleavage in distal Golgi compartments. The propeptide is not a requirement for normal processing of the receptor and does not prevent ligands from binding to the SorCS3 precursor form. Expression of wt and chimeric receptors further suggests that SorCS3 predominates on the plasma membrane, exhibits slow internalization and does not engage in intracellular trafficking. SorCS3 emerges as a new neurotrophin binding Vps10p‐domain receptor functionally distinct from its relatives Sortilin and SorLA.
L‐dopa and dopamine enhance the formation of aggregates under proteasome inhibition in PC12 cells
Authors: Yoshimoto Yuko , Nakaso Kazuhiro , Nakashima Kenji
Published: January 2005

The formation of inclusion bodies in dopaminergic neurons is associated with the pathogenesis of Parkinson's disease. In order to clarify the role of dopamine/L‐dopa in the formation of protein aggregates, we investigated dopamine/L‐dopa‐related aggregation using an experimental inclusion model. The inhibition of tyrosine hydroxylase (TH) by α‐methyltyrosine dramatically decreased MG132‐induced aggregate formation. In addition, the inhibition of TH caused the upregulation of proteasomes in cultured cells and the dopamine/L‐dopa induced non‐enzymatic polymerization of ubiquitin. This inhibition did not affect cell viability. These results suggest that dopamine/L‐dopa might enhance aggregate formation, and that intracellular aggregates may not be toxic to cells.
Empirical limits for template‐based protein structure prediction: the CASP5 example
Authors: Contreras-Moreira B. , Ezkurdia I. , Tress M.L. , Valencia A.
Published: January 2005

Most protein structure prediction methods use templates to assist in the construction of protein models. In this paper, we analyse the current state of template‐based modelling approaches and reach an estimate of the empirical limits of these methods. Our analysis show that current prediction methods are already reaching these empirical accuracy limits in the easier cases, where finding a close homologue to the native target structure is not a problem. However, we find that even in the absence of alignment errors and using optimal templates, template‐based methods have intrinsic limitations, suggesting that other methodologies, such as ab initio procedures, must be used if accuracy is ultimately to be improved.
A redox switch hypothesis for the origin of two light reactions in photosynthesis
Authors: Allen John F.
Published: January 2005

Photosynthesis provides energy in the Earth's biosphere and oxygen in its atmosphere. For oxygen to be produced, two different light reactions must operate simultaneously and in series. Known anaerobic, photosynthetic bacteria contain one or other of these photosystems, but never both. Here, I propose that the two photosystems diverged, in structure and function, from a common ancestor, within a single, continuous, anaerobic lineage. In such cells, living examples of which are predicted, the two photosystems are isoenzymes encoded by orthologous genes under co‐ordinated, redox regulatory control. A redox switch responds to defined environmental conditions and selects which set of genes is expressed. In these cells, the two photosystems are thus synthesised at different times. It is further proposed that the origin of oxygen‐evolving photosynthesis was a simple mutation that disabled the redox switch, permitting simultaneous expression of the two sets of genes. The two, newly co‐existing photosystems became connected by shared electron carriers, allowing generation of electrochemical potential high enough to oxidise water; an inexhaustible supply of reductant; and the selective advantages and pressures of an aerobic world.
Global gene expression profile of Yersinia pestis induced by streptomycin
Authors: Qiu Jingfu , Zhou Dongsheng , Han Yanping , Zhang Ling , Tong Zongzhong , Song Yajun , Dai Erhei , Li Bei , Wang Jin , Guo Zhaobiao , Zhai Junhui , Du Zongmin , Wang Xiaoyi , Yang Ruifu
Published: January 2005

Plague, caused by Y ersinia pestis, is one of the most dangerous diseases that impressed a horror onto human consciousness that persists to this day. Cases of plague can be normally controlled by timely antibiotic administration. Streptomycin is the first-line antibiotic for plague treatment. In this study, a DNA microarray was used to investigate the changes in the gene expression profile of Y. pestis upon exposure to streptomycin. A total of 345 genes were identified to be differentially regulated, 144 of which were up-regulated, and 201 down-regulated. Streptomycin-induced transcriptional changes occurred in genes responsible for heat shock response, drug/analogue sensitivity, biosynthesis of the branched-chain amino acids, chemotaxis and mobility and broad regulatory functions. A wide set of genes involved in energy metabolism, biosynthesis of small macromolecules, synthesis and modification of macromoclecules and degradation of small and macro molecules were among those down-regulated. The results reveal general changes in gene expression that are consistent with known mechanisms of action of streptomycin and many new genes that are likely to play important roles in the response to streptomycin treatment, providing useful candidates for investigating the specific mechanisms of streptomycin action.
Cerebellar granule cell and Bergmann glial cell maturation in the rat is disrupted by pre‐ and post‐natal exposure to moderate levels of ethanol
Authors: González‐Burgos I. , Alejandre‐Gómez M.
Published: January 2005

Migration of the external granular layer cells in the cerebellum of rats was delayed after exposure to moderate levels of ethanol during a pre‐gestational period, through gestation and lactation until weaning. After ethanol withdrawal, cell soma and dendrites were observed to be larger in granule cells. Likewise, Bergmann glia showed several cytoarchitectonic features suggesting cell immaturity, as well as some apparent compensatory plastic responses after ethanol withdrawal. These effects may be due to ethanol impairing neurotrophin‐mediated processes during cerebellar development that could lead to alterations in Purkinje cell structure and activity, and thereafter in the psychoneural functions in which the cerebellar cortex is involved.
The vulnerability of striatal projection neurons and interneurons to excitotoxicity is differentially regulated by dopamine during development
Authors: Pezzi Susana , Checa Nuria , Alberch Jordi
Published: January 2005

The maturation of striatal projection neurons and interneurons is influenced by the development and integrity of their connectivity. In the present work, we have analyzed the modulation of striatum vulnerability to quinolinate (QUIN)‐induced excitotoxicity in different neuronal populations by the nigrostriatal dopaminergic pathway during postnatal development. A single striatal lesion with 6‐hydroxydopamine (6‐OHDA) at the second postnatal day (P) 2 or QUIN at P7 induced a reduction in the striatal volume at P30, whereas an additive effect was observed when these two lesions were performed in the same animal. The analysis of different striatal neuronal populations showed that the excitotoxic lesion induced by QUIN over projection neurons stained with calbindin was partially reverted by the previous injection of 6‐OHDA at P2. However, cholinergic interneurons were affected neither by the lack of dopamine innervation nor by QUIN treatment. This neuronal population also remained intact after the double lesion. In contrast, the number of other type of striatal interneurons, parvalbumin‐positive neurons, were reduced by the dopaminergic ablation and also by the QUIN‐induced excitotoxicity and this effect was additive after the double lesion when it was measured at P30. On the other hand, we studied the effect on the striatal outputs measuring the density of substance P‐positive fibers in the substantia nigra and enkephalin‐positive fibers in the globus pallidus. A reduction in substance P‐positive fibers was observed in 6‐OHDA injected animals, while the density of enkephalin‐positive fibers was only decreased after QUIN treatment. The double lesion did not modify the effects of the single lesions. In conclusion, our results show that dopamine modulates the vulnerability to excitotoxicity during striatal postnatal development, and this effect is specific for projection neurons. Furthermore, striatonigral and striatopallidal pathways are differentially regulated by the activation of dopamine or glutamate receptors.
Low‐dose secnidazole in the treatment of bacterial vaginosis
Authors: Núñez J.T. , Gómez G.
Published: January 2005

Objective

To determine whether bacterial vaginosis could be cured with a single 1‐g oral dose of secnidazole.

Material and methods

A total of 80 women were recruited at the outpatient gynecologic clinic of Manuel Noriega Hospital, Maracaibo, Venezuela. Diagnosis and patient enrollment were based on the Amsel criteria. The participants were randomized to 2 groups. In group 1 (n=44) participants received a single 1‐g oral dose and in group 2 (n=32) participants received a single 2‐g oral dose of secnidazole. Clinical cure was defined as the absence of the characteristic symptoms (a bad odor and a grossly abnormal discharge) and at least 2 of the following: vaginal pH less than 4.5, no fish odor on addition of KOH, and no Gardnerella vaginalis or clue cells on wet‐mount examination. Cytologic cure was defined as an absence of G. vaginalis on a Papanicolaou (Pap) smear.

Results

Clinical cure was experienced by 95.5% of the women who received the 1‐g oral dose and by 97.4% of the women who received the 2‐g oral dose of secnidazole. There was no significant difference between the groups in the clinical resolution of bacterial vaginosis. Following treatment, results were negative for G. vaginalis in 94.7% of the women. In group 1, 41 women (93.2%), and in group 2, 31 women (96.9%) had cytologic cure. The Pap smear revealed G. vaginalis in 3 of the women in group 1 and 1 of the women in group 2 (P=0.47). Twenty‐seven women (35.5%) reported mild side effects. More women had adverse effects in group 1 (n=16) than in group 2 (n=11) but this difference was not statistically significant.

Conclusion

This clinical study showed that a single 1‐g oral dose of secnidazole is effective to cure bacterial vaginosis associated with G. vaginalis.
Endothelin‐1 is secreted after total knee arthroplasty regardless of the use of a tourniquet
Authors: Matziolis G. , Drahn T. , Schröder J. H. , Krocker D. , Tuischer J. , Perka C.
Published: January 2005

Early infections and wound healing disorders after implantation of a total knee replacement occur regardless of the intraoperative use of a tourniquet. The biochemical regulatory processes responsible for the disturbances in microcirculation and thus the potential therapeutic options have yet to be elucidated. The hypothesis of the present paper was that endothelin‐1 (ET‐1), a mediator of microcirculation disturbances in parenchymatous organs, also is released after major operations on peripheral joints.

The concentration of ET‐1 in the plasma was determined preoperatively and at 10 postoperative time points (5 min–48h) with (group A, n = 10) and without the use of a tourniquet (group B, n = 10). The ET‐1 concentration achieved its maximum 6h after opening the tourniquet, which corresponded to 3.3 times the preoperative value. Without a tourniquet, the concentration maximum (2.9 times the baseline value) was achieved already 1.5 h after the end of the operation. However, the total amount of ET‐1 secreted over 24 h was identical in both groups (p > 0.5).

We conclude that the tissue hypoxia resulting from the use of a tourniquet modulates ET‐1 secretion, but that traumatization during the operation has a much stronger influence on the total amount secreted.

ET‐1 antagonists thus should be discussed for the drug prophylaxis of wound healing disorders, regardless of the use of a tourniquet. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Propagation and field performance of own-rooted peach trees
Authors: Tsipouridis C. G. , Isaakidis A. , Manganaris A. , Therios I. , Michailidis Z.
Published: January 2005

Ten peach and nectarine (Prunus persica L. Batsh) cultivars: Arm King, Early Crest, Early Gem, Flavor Crest, May Crest, May Grand, Red Gold, Red Haven, Spring Crest and Sun Crest, were propagated by both hardwood cuttings (HC) and by bud grafting onto peach seedlings. Significant differences were observed for rooting among cultivars and applied IBA. Degree of blooming and yield were higher for HC propagated own-rooted trees when compared with budded trees in the first 6 years of fruiting. Budded trees increased in size faster than HC trees but were less productive. Yield, yield efficiency and fruit size were not only cultivar specific, but were also affected by the propagation method, being higher for own-rooted trees in most cultivars. Tree mortality was generally higher for budded trees. No significant differences were found in mineral absorption efficiency, time of blooming, fruit firmness, acidity and sugar level between own-rooted and budded trees. Results based on percent rooting of HC, yield, fruit size, growth and tree mortality suggest that own-rooted HC trees should be an acceptable tree type for commercial orchards, especially for the cultivars Sun Crest, Spring Crest and Red Haven.
Plant density and thinning regime effect on maize (Zea mays) grain and fodder yield
Authors: Njoka E. M. , Muraya M. M. , Okumu M.
Published: January 2005

Maize (Zea mays L.) plant density is an important management practice for successful grain and forage production. The objective of this study was to determine the most suitable maize seeding and time of thinning maize as fodder in grain maize crops. Previously the focus in this area has been on grain and silage production, and consequently information on the production of fodder in grain maize crops is limited. This study therefore aims to investigate the growth of high density maize for fodder production through thinning and subsequent grain yield. A plant density experiment in randomised complete block design was carried out at Egerton University, Njoro, using a Kenyan hybrid (H511) where 4 densities (44 444, 88 888, 177 777 and 355 555 plants/ha) and 4 thinning regimes (V4, V6, V10 and VT phenological stages) were used. The densities vary through number of seed per hill (i.e. 1, 2, 4 and 8 seeds/hill, not row or plant spacing) and spacing of 30 cm between the hills within the row and 75 cm between the rows was used. Maize plants were thinned following the appropriate thinning regime to leave 1 plant per hill, giving a plant density of 44 444 plants/ha in all treatments after thinning. Their biomass was then determined. The single plants per hill left, as a normal farmers practice, were used to determine grain yield at harvest. Plant density of 355 552 plants/ha, with a treatment structure of 4 seeds/hill and thinned at the VT phenological stage gave the highest thinning biomass per hectare, while 44 444 plants/ha, with a treatment structure of 1 seed/hill and no thinning, gave the highest grain yield. The thinning regime of the V10 phenological stage and 2 seeds/hill thinned at the VT phenological stage gave appreciable amount of fodder and grain yields. This study has shown that with particular seeding densities and thinning regimes, production of both fodder and grain is possible.
Linking Tasmanian potato and poppy yields to selected soil physical and chemical properties
Authors: Cotching W. E. , Sparrow L. A. , Hawkins K. , McCorkell B. E. , Rowley W.
Published: January 2005

Selected soil properties and paddock management characteristics were measured for 121 potato and poppy crops in north and northwest Tasmania to see if variation in these characteristics explain variation in crop yield. The soil properties we selected were those that previous work found had changed the most as a result of cropping and, therefore, may be affecting yield on the particular soil type. The soil properties and management characteristics that were significantly correlated with crop yield varied with crop and soil type. None of the soil characters had correlation coefficients greater than 0.63, probably reflecting the capacity of individual farmers to overcome particular soil limitations through their management of tillage, nutrition, irrigation, weeds and pathogens. On ferrosols, a visual score of soil structure was significantly correlated with potato yield (r = 0.57) and exchangeable aluminium was significantly correlated with poppy yield (r = 0.63). Exchangeable calcium (r = 0.54) and penetration resistance (r = 0.38) correlated positively and topdressed nitrogen (r = –0.49) correlated negatively with poppy alkaloid assay, an important determinant of overall poppy yield. On dermosols, depth to 2000 kPa penetration resistance (r = 0.60) and fertiliser P (r = –0.67) were correlated with potato yield, structure score correlated with poppy yield (r = 0.59), and penetration resistance with poppy assay (r = 0.52). On sodosols, fertiliser K (r = –0.41 and r = 0.55) and N (r = –0.45 and 0.42) correlated negatively with poppy yield and positively with poppy assay. On clay loam soils such as dermosols and ferrosols, increased topsoil cloddiness appears to be having a deleterious effect on crop yield. Cloddiness is readily assessed on these soils using the structure scorecard, which could therefore become a practical diagnostic test for farmers and advisers.
Effects of climatic factors, fluctuating water availability and partial defoliation on the diurnal radial growth pattern of carrot (Daucus carota) taproots
Authors: Gracie A. J. , Brown P. H.
Published: January 2005

Carrot taproots are prone to radial longitudinal tissue fractures (splitting). The longitudinal alignment of the fractures is consistent with the tangential stress induced by radial growth in the annular cambium. In this study linear variable differential transformers were used to monitor the diurnal radial growth pattern of mature carrot taproots. The diurnal growth pattern was characterised by rapid expansion during the night (dark) period and small shrinkage during the light period. The magnitude of the daily shrinkage was positively correlated with both vapour pressure deficit and global radiation. A positive correlation between the rate of taproot expansion during the night period and global radiation level the preceding day was also recorded. Water stress reduced the taproot night time expansion rate, but the taproot of water stressed plants expanded rapidly when watered to field capacity. Partial defoliation of plants at midday resulted in immediate expansion of the taproot, however, the daily growth rates of the partially defoliated plants was less than untreated control plants over the following 3 days. It was concluded that the short-term changes in taproot diameter could be used to infer changes in tangential stresses and therefore taproot splitting propensity.
The economic value of haying and green manuring in the integrated management of annual ryegrass and wild radish in a Western Australian farming system
Authors: Monjardino M. , Pannell D. J. , Powles S. B.
Published: January 2005

Most cropping farms in Western Australia must deal with the management of herbicide-resistant populations of weeds such as annual ryegrass (Lolium rigidum) and wild radish (Raphanus raphanistrum). Farmers are approaching the problem of herbicide resistance by adopting integrated weed management systems, which allow weed control with a range of different techniques. These systems include non-herbicide methods ranging from delayed seeding and high crop seeding rates to the use of non-cropping phases in the rotation. In this paper, the Multi-species RIM (resistance and integrated management) model was used to investigate the value of including non-cropping phases in the crop rotation. Non-crop options investigated here were haying and green manuring. Despite them providing excellent weed control, it was found that inclusion of these non-cropping phases did not increase returns, except in cases of extreme weed numbers and high levels of herbicide resistance.
Ryegrass endophyte (Neotyphodium lolii) alkaloids and mineral concentrations in perennial ryegrass (Lolium perenne) from southwest Victorian pasture
Authors: Reed K. F. M. , Walsh J. R. , Cross P. A. , McFarlane N. M. , Sprague M. A.
Published: January 2005

On all of 120 farms in south-west Victoria that were selected at random and sampled during autumn and winter over 2 years, perennial ryegrass was present in the pasture and tested positive for the presence of the naturally occurring ryegrass endophyte, Neotyphodium lolii (mean frequency 78%). Ryegrass staggers were reported on 33% (1999) and 43% (2000) of the surveyed farms. Clinically significant concentrations of lolitrem B were detected in perennial ryegrass samples with concentrations in the range 0–4.44 mg/kg. Concentration exceeded 1.8 mg/kg in 37% of pastures indicating an inherent, widespread problem for livestock farmers. Concentration was independent of endophyte frequency, pasture age, pasture height, annual rainfall and origin of sown cultivar. Ergovaline was detected in most of the perennial ryegrass samples with concentrations up to 3.90 mg/kg. In 1999, the mean concentration of ergovaline was 0.76 (± 0.70) mg/kg with 33% of pastures having a level >0.4 mg/kg, the level associated with heat stress in cattle. In 2000, sampling was carried out later in the year than for the 1999 survey and the mean concentration of ergovaline was 0.12 (± 0.10) mg/kg; 3% of samples exceeded 0.4 mg/kg. The mean concentration of peramine was 13.7 (± 6.6) mg/kg in the 1999 survey and 4.2 (± 5.1) mg/kg in the 2000 survey. Mineral analysis indicated that perennial ryegrass nutrition was inadequate with regard to phosphorous on 17% of the dairy pastures and on 37% of the sheep/beef pastures. Potassium was deficient in perennial ryegrass on 5 and 37% of dairy and sheep/beef pastures respectively. For perennial ryegrass in sheep/beef pastures, 25% were deficient in sulphur. For lactating cattle having only perennial ryegrass as a food source, phosphorous and copper concentrations in the grass were inadequate on 80% of the pastures. Calcium, zinc, magnesium, potassium and sulphur concentrations in perennial ryegrass were also inadequate on some pastures. However, with 1 exception, the ratio [K/(Ca+Mg) expressed as equivalents] was less than 2.2, the level associated with the development of hypomagnesemia. Hypomagnesemia (grass tetany) was therefore unlikely to be a major cause of the staggers syndrome. Lolitrem B was negatively correlated with grass potassium concentration (P<0.001). Ergovaline was negatively correlated with date of sampling (P<0.001). Peramine concentration was positively correlated with endophyte frequency, the potassium and sodium concentrations in perennial ryegrass and negatively correlated with date of sampling. The need for research on the economic impact and management of pasture contaminated with ryegrass endophyte toxins is discussed.
The DNA/RNA-binding protein MSY2 marks specific transcripts for cytoplasmic storage in mouse male germ cells
Authors: Yang Juxiang , Medvedev Sergey , Reddi P. Prabhakara , Schultz Richard M. , Hecht Norman B.
Published: January 2005

During spermatogenesis, male germ cells temporally synthesize many proteins as they differentiate through meiosis and become spermatozoa. The germ cell Y-box protein, MSY2, constituting ≈0.7% of total protein in male germ cells, binds to a consensus promoter element, and shows a general lack of RNA-binding specificity. Combining immunoprecipitation and suppressive subtractive hybridization, we identified populations of germ cell mRNAs that are not bound or bound by MSY2. The former population is enriched in cell growth and ubiquitously expressed mRNAs, whereas the latter population is enriched for stored or translationally delayed, male gamete-specific transcripts. Chromatin precipitation assays reveal that most of the MSY2 target mRNAs are transcribed from genes containing the Y-box DNA-binding motif in their promoters. In transgenic mice, mRNAs encoding exogenous GFP are directed or not directed into the MSY2-bound fraction by promoters containing or lacking the Y-box motif, respectively. We propose that MSY2 marks specific mRNAs in the nucleus for cytoplasmic storage, thereby linking transcription and mRNA storage/translational delay in meiotic and postmeiotic male germ cells of the mouse.
Laminin α1 globular domains 4–5 induce fetal development but are not vital for embryonic basement membrane assembly
Authors: Schéele Susanne , Falk Mats , Franzén Ahnders , Ellin Fredrik , Ferletta Maria , Lonai Peter , Andersson Björn , Timpl Rupert , Forsberg Erik , Ekblom Peter
Published: January 2005

During early mouse embryogenesis, each laminin (Lm) chain of the first described Lm, a heterotrimer of α1, β1, and γ1 chains (Lm-1), is essential for basement membrane (BM) assembly, which is required for pregastrulation development. Individual domains may have other functions, not necessarily structural. The cell binding C terminus of Lm α1 chain contains five Lm globular (LG) domains.
In vitro
, α1LG1–3 domains bind integrins, and α1LG4 binds dystroglycan, heparin, and sulfatides. A prevailing hypothesis is that α1LG4 is crucial as a structural domain for BM assembly, whereas integrin-binding sites conduct signaling. The
in vivo
role of α1LG4–5 (also called E3) has not been studied. Mice lacking α1LG4–5 were therefore made. Null embryos implanted, but presumptive epiblast cells failed to polarize and did not survive past day 6.5. BM components including truncated Lm α1 were detected in Reichert's membrane. Surprisingly, embryonic BM assembly between visceral endoderm and stem cells was normal in null embryos and in embryoid bodies of α1LG4–5-null embryonic stem cells. Yet, stem cells could not develop into polarized epiblast cells. Thus, α1LG4–5 provides vital signals for the conversion of stem cells to polarized epithelium.
Ancestry and progeny of nutrient amino acid transporters
Authors: Boudko Dmitri Y. , Kohn Andrea B. , Meleshkevitch Ella A. , Dasher Michelle K. , Seron Theresa J. , Stevens Bruce R. , Harvey William R.
Published: January 2005

The biosynthesis of structural and signaling molecules depends on intracellular concentrations of essential amino acids, which are maintained by a specific system of plasma membrane transporters. We identify a unique population of nutrient amino acid transporters (NATs) within the sodium-neurotransmitter symporter family and have characterized a member of the NAT subfamily from the larval midgut of the Yellow Fever vector mosquito,
Aedes aegypti
(aeAAT1, AAR08269), which primarily supplies phenylalanine, an essential substrate for the synthesis of neuronal and cuticular catecholamines. Further analysis suggests that NATs constitute a comprehensive transport metabolon for the epithelial uptake and redistribution of essential amino acids including precursors of several neurotransmitters. In contrast to the highly conserved subfamily of orthologous neurotransmitter transporters, lineage-specific, paralogous NATs undergo rapid gene multiplication/substitution that enables a high degree of evolutionary plasticity of nutrient amino acid uptake mechanisms and facilitates environmental and nutrient adaptations of organisms. These findings provide a unique model for understanding the molecular mechanisms, physiology, and evolution of amino acid and neurotransmitter transport systems and imply that monoamine and GABA transporters evolved by selection and conservation of earlier neuronal NATs.
Attenuation of cardiac remodeling after myocardial infarction by muscle LIM protein-calcineurin signaling at the sarcomeric Z-disc
Authors: Heineke Joerg , Ruetten Hartmut , Willenbockel Christian , Gross Sandra C. , Naguib Marian , Schaefer Arnd , Kempf Tibor , Hilfiker-Kleiner Denise , Caroni Pico , Kraft Theresia , Kaiser Robert A. , Molkentin Jeffery D. , Drexler Helmut , Wollert Kai C.
Published: January 2005

Adverse left ventricular (LV) remodeling after myocardial infarction (MI) is a major cause for heart failure. Molecular modifiers of the remodeling process remain poorly defined. Patients with heart failure after MI have reduced LV expression levels of muscle LIM protein (MLP), a component of the sarcomeric Z-disk that is involved in the integration of stress signals in cardiomyocytes. By using heterozygous MLP mutant (MLP
+/—
) mice, we explored the role of MLP in post-MI remodeling. LV dimensions and function were similar in sham-operated WT and MLP
+/—
mice. After MI, however, MLP
+/—
mice displayed more pronounced LV dilatation and systolic dysfunction and decreased survival compared with WT mice, indicating that reduced MLP levels predispose to adverse LV remodeling. LV dilatation in MLP
+/—
mice was associated with reduced thickening but enhanced elongation of cardiomyocytes. Activation of the stress-responsive, prohypertrophic calcineurin–nuclear factor of activated T-cells (NFAT) signaling pathway was reduced in MLP
+/—
mice after MI, as shown by a blunted transcriptional activation of NFAT in cardiomyocytes isolated from MLP
+/—
/NFAT-luciferase reporter gene transgenic mice. Calcineurin was colocalized with MLP at the Z-disk in WT mice but was displaced from the Z-disk in MLP
+/—
mice, indicating that MLP is essential for calcineurin anchorage to the Z-disk.
In vitro
assays in cardiomyocytes with down-regulated MLP confirmed that MLP is required for stress-induced calcineurin–NFAT activation. Our study reveals a link between the stress sensor MLP and the calcineurin–NFAT pathway at the sarcomeric Z-disk in cardiomyocytes and indicates that reduced MLP–calcineurin signaling predisposes to adverse remodeling after MI.
Lack of TCF2/vHNF1 in mice leads to pancreas agenesis
Authors: Haumaitre C. , Barbacci E. , Jenny M. , Ott M. O. , Gradwohl G. , Cereghini S.
Published: January 2005

Heterozygous mutations in the human POU-homeobox
TCF2
(
vHNF1, HNF1
β) gene are associated with maturity-onset diabetes of the young, type 5, and abnormal urogenital tract development. Recently, pancreas atrophies have been reported in several maturity-onset diabetes of the young type 5 patients, suggesting that
TCF2
is required not only for adult pancreas function but also for its normal development.
Tcf2
-deficient mice die before gastrulation because of defective visceral endoderm formation. To investigate the role of this factor in pancreas development, we rescued this early lethality by tetraploid aggregation. We show that TCF2 has an essential function in the first steps of pancreas development, correlated with its expression domain that demarcates the entire pancreatic buds from the earliest stages. Lack of TCF2 results in pancreas agenesis by embryonic day 13.5. At earlier stages, only a dorsal bud rudiment forms transiently and expresses the transcription factors
Ipf1
and
Hlxb9
but lacks the key transcription factor involved in the acquisition of a pancreatic fate,
Ptf1a
, as well as all endocrine precursor cells. Regional specification of the gut also is perturbed in
Tcf2
-/-
embryos as manifested by ectopic expression of
Shh
and lack of
Ihh
and
Ipf1
in the posterior stomach and duodenum. Our results highlight the requirement of
Tcf2
for ensuring both accurate expression of key regulator molecules in the stomach–duodenal epithelium and proper acquisition of the pancreatic fate. This study provides further insights into early molecular events controlling pancreas development and may contribute to the development of cell-replacement strategies for diabetes.
Reconstructing early sponge relationships by using the Burgess Shale fossil
Eiffelia globosa
, Walcott
Authors: Botting Joseph P. , Butterfield Nicholas J.
Published: January 2005

The relationships of the sponge classes are controversial, particularly between the calcareous and siliceous sponges. Specimens of the putative calcarean
Eiffelia globosa
Walcott from the Burgess Shale show the presence of diagnostic hexactinellid spicules integrated into the skeletal mesh. The arrangement of these spicules in
Eiffelia
is shown to be precisely equivalent to that of early protospongioid hexactinellids, and sponge growth occurred through an identical pattern to produce identical skeletal body morphology. The difference in spicule composition of the classes is interpreted through the observation of taphonomic features of
Eiffelia
that suggest the presence of at least two mineralogically distinct layers within the spicules. These results support molecular analyses that identify the calcarean-silicisponge transition as the earliest major sponge branch and suggest that the heteractinids were paraphyletic with respect to the Hexactinellida.
The Wnt/β-catenin signaling pathway targets PPARγ activity in colon cancer cells
Authors: Jansson Emmelie Å. , Are Alexandra , Greicius Gediminas , Kuo I-Chun , Kelly Denise , Arulampalam Velmurugesan , Pettersson Sven
Published: January 2005

Control of colon cell fate in adenocarcinomas is disrupted, in part, due to aberrant Wnt/β-catenin signaling. The nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) has been implicated in the development of colon cancers. In the adenomatous polyposis coli multiple intestinal neoplasia (APCMin) mouse cancer model, PPARγ expression in the colonic mucosa is markedly altered. In addition, PPARγ protein levels are elevated, possibly through sequestration by activated β-catenin in colon cancer cell lines. Induction of the Wnt/β-catenin pathway by LiCl also elevated PPARγ levels and induced PPARγ-dependent reporter and endogenous target genes. Mechanistically, PPARγ, through interactions with β-catenin and T cell transcription factor (Tcf)-4, may be a determinant of cell fate and is likely a target of the Wnt pathway in cancer cells.
Identifying tissue-selective transcription factor binding sites in vertebrate promoters
Authors: Smith Andrew D. , Sumazin Pavel , Zhang Michael Q.
Published: January 2005

We present a computational method aimed at systematically identifying tissue-selective transcription factor binding sites. Our method focuses on the differences between sets of promoters that are associated with differentially expressed genes, and it is effective at identifying the highly degenerate motifs that characterize vertebrate transcription factor binding sites. Results on simulated data indicate that our method detects motifs with greater accuracy than the leading methods, and its detection of strongly overrepresented motifs is nearly perfect. We present motifs identified by our method as the most overrepresented in promoters of liver- and muscle-selective genes, demonstrating that our method accurately identifies known transcription factor binding sites and previously uncharacterized motifs.
An intermolecular base triple as the basis of ligand specificity and affinity in the guanine- and adenine-sensing riboswitch RNAs
Authors: Noeske Jonas , Richter Christian , Grundl Marc A. , Nasiri Hamid R. , Schwalbe Harald , Wöhnert Jens
Published: January 2005

Riboswitches are highly structured RNA elements that control the expression of many bacterial genes by binding directly to small metabolite molecules with high specificity and affinity. In
Bacillus subtilis
, two classes of riboswitches have been described that discriminate between guanine and adenine despite an extremely high degree of homology both in their primary and secondary structure. We have identified intermolecular base triples between both purine ligands and their respective riboswitch RNAs by NMR spectroscopy. Here, specificity is mediated by the formation of a Watson–Crick base pair between the guanine ligand and a C residue or the adenine ligand and a U residue of the cognate riboswitch RNA, respectively. In addition, a second base-pairing interaction common to both riboswitch purine complexes involves a uridine residue of the RNA and the N3/N9 edge of the purine ligands. This base pairing is mediated by a previously undescribed hydrogen-bonding scheme that contributes to the affinity of the RNA–ligand interaction. The observed intermolecular hydrogen bonds between the purine ligands and the RNA rationalize the previously observed change in specificity upon a C to U mutation in the core of the purine riboswitch RNAs and the differences in the binding affinities for a number of purine analogs.
Inhibition of homologous recombination by variants of the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs)
Authors: Convery Erin , Shin Euy Kyun , Ding Qi , Wang Wei , Douglas Pauline , Davis Laurie S. , Nickoloff Jac A. , Lees-Miller Susan P. , Meek Katheryn
Published: January 2005

Two major DNA double-strand break repair pathways exist in all eukaryotes, nonhomologous DNA end joining (NHEJ) and homologous recombination (HR). Although both pathways can function throughout the cell cycle, NHEJ predominates in G0/G1(when a replicated sister chromatid is unavailable), whereas HR makes a more substantial contribution in S and G2. How a cell chooses between these two important DNA repair pathways is largely unknown. DNA-dependent protein kinase (DNA-PK) is critical for NHEJ. Here, we describe two conserved splice variants of a catalytic subunit of DNA-PK (DNA-PKcs) that are expressed predominately in nondividing cells. Although both encode stable products, neither reverses the NHEJ defects in DNA-PKcs-deficient cells. In fact, cells expressing one of the DNA-PKcs variants are slightly more radiosensitive than cells completely deficient in DNA-PKcs. We investigated whether cells expressing the DNA-PKcs variants had any other DNA repair deficits and found that these cells are considerably more sensitive to both etoposide and mitomycin C than cells that express no DNA-PKcs at all. Because repair of DNA damage induced by these two agents requires intact HR, we tested whether the NHEJ-defective variants of DNA-PKcs inhibit double-strand break-induced HR in an integrated substrate. In cells expressing the NHEJ-defective variants, HR was markedly reduced. Because the splice variants are expressed highly only in nondividing cells, quiescent cells would be afforded a mechanism to inhibit repair by means of HR when sister chromatids are not available as templates for accurate repair with low risk of genome rearrangement, thereby enhancing genome stability.