bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endogenous corticosteroid biosynthesis in subjects after bilateral adrenalectomy
Authors: Freel E. M. , Bernhardt M. , Ingram R. , Wallace A. M. , Fraser R. , Davies E. , Connell J. M. C. 
Published: March 2007

SummaryObjective  Corticosteroids can be synthesized in extra‐adrenal tissues but the contribution of this to circulating levels in humans is not known. Previous in vitro studies suggest that the ‘hybrid’ corticosteroid 18‐oxocortisol (18‐oxoF) is produced from cortisol by aldosterone synthase. We looked for evidence of extra‐adrenal production of this and other corticosteroids in 10 subjects stable on long‐term glucocorticoid replacement following bilateral adrenalectomy.Methods  In phase 1, patients were maintained on cortisol alone (30 mg/day), in phase 2 dexamethasone (2 mg/day), and in phase 3, both cortisol and dexamethasone. Each phase lasted 3 days.Measurements  On the last day of each phase, 24‐h urine collection was performed for analysis of steroid metabolite excretion [using gas chromatography–mass spectrometry (GCMS)] and plasma aldosterone and renin were measured (by radioimmunoassay).Results  Cortisol metabolite excretion rate [tetrahydrocortisone (THE) + tetrahydrocortisol (THF) + allotetrahydrocortisol (aTHF)] fell from 9169 nmol/24 h in phase 1 to 22 nmol/24 h in phase 2, rising to 6843 nmol/24 h in phase 3. Tetrahydroaldosterone (THAldo) excretion was readily detectable and did not alter significantly between phases (26·5, 23·5 and 28·5 nmol/24 h, respectively; P = 0·474). 18‐Hydroxycortisol (18‐OHF) excretion was easily detectable in phases 1 and 3 (252·5 and 212 nmol/24 h), falling in phase 2 (12 nmol/24 h). 18‐oxoF excretion rates were lower but followed a similar pattern (1·62, 0·085 and 1·785 nmol/24 h in phases 1, 2 and 3, respectively).Conclusions  Significant levels of adrenal steroids are found in adrenalectomized subjects. We speculate that this occurs at extra‐adrenal sites or in residual adrenal cortex tissue in an ACTH‐independent manner. Our data suggest that aldosterone synthase, acting on cortisol, is the source of 18‐oxoF and 18‐OHF in these subjects. Further studies of corticosteroid production within adrenalectomized subjects, looking for evidence of adrenal regrowth or residual adrenal tissue, are justified.
Free fatty acids inhibit adrenocorticotropin and cortisol secretion stimulated by physical exercise in normal men
Authors: Coiro V. , Casti A. , Rubino P. , Manfredi G. , Maffei M. L. , Melani A. , Saccani Jotti G. , Chiodera P. 
Published: March 2007

SummaryBackground  The basal circulating levels of ACTH and cortisol, but not the ACTH/cortisol response to hCRH, are significantly reduced by free fatty acid (FFA) infusion.Objective  To verify whether FFA infusion modifies the ACTH/cortisol response to physical exercise, a well‐known activator of the HPA axis at suprapituitary level.Design  Exercise tests on a bicycle ergometer during infusion of a lipid‐heparin emulsion (LHE) (experimental test) or normal saline (NaCl 0·9%) (control test).Setting  Department of Cardiology at the University‐Hospital.Subjects  Seven healthy male subjects aged 25–33 years.Interventions  On two mornings, at weekly intervals, LHE or saline were infused for 60 min; infusion started 10 min before exercise test on a bicycle ergometer, which lasted about 15 min.Main outcome measures  Circulating ACTH/cortisol levels and physiological variables during physical exercise.Results  FFA levels (0·4 ± 0·1 mEq/l) remained constant during control test, whereas they progressively rose (peak at 60 min, 2·7 ± 1·0 mEq/l) during LHE infusion. Neither basal nor exercise‐induced changes in physiological variables were modified by LHE infusion. Both ACTH and cortisol increased during exercise, with peak levels at 20 min and 30 min (control test: 103% and 42%, P < 0·001; experimental test: 28·5% and 18·6%, P < 0·05 higher than baseline, respectively).Both ACTH and cortisol responses were significantly lower in the experimental than in the control test (at 20 min P < 0·002 and at 30 min P < 0·05 for ACTH; at 20 min P < 0·05 and at 30 min, 40 min and 50 min P < 0·001 for cortisol).Conclusions  These data represent the first demonstration of an inhibitory action of increased circulating FFA levels on the HPA axis under stimulatory conditions (i.e. physical exercise, a challenge acting at suprapituitary level). In contrast, previous studies did not show FFA effects on the CRH‐induced ACTH/cortisol response. Therefore, our data suggest negative effects of FFAs on the HPA axis at hypothalamic or higher centres in the central nervous system.
Clinical and genetic characteristics of congenital hypothyroidism due to mutations in the thyroid peroxidase (TPO) gene in Israelis
Authors: Tenenbaum‐Rakover Yardena , Mamanasiri Sunee , Ris‐Stalpers Carrie , German Alina , Sack Joseph , Allon‐Shalev Stavit , Pohlenz Joachim , Refetoff Samuel 
Published: March 2007

SummaryObjectives  Iodide organification defect (IOD) is characterized by a reduced ability of the thyroid gland to retain iodide and results in hypothyroidism. Mutations in the thyroid peroxidase (TPO) gene are a frequent cause of IOD. While TPO mutations have been identified in various populations, none have been reported in Israeli patients with IOD. The objectives of this study were to characterize the molecular basis of IOD in an Israeli Arab‐Muslim population and to analyse the clinical, neurological and imaging data of patients with TPO mutations followed for up to 29 years.Patients  Twenty‐two patients from six core families with congenital hypothyroidism (CH) and IOD living in the same region.Design and measurements  All subjects underwent clinical, hormonal and imaging evaluation. The TPO gene was directly sequenced and the presence of specific mutations among family members was determined by restriction fragment length polymorphism (RFLP).Results  All patients had congenital and persistent primary hypothyroidism. The thyroid gland was demonstrated in all subjects by technetium (99mTc) scans. A positive perchlorate discharge test (mean 87%) was indicative of IOD. Enlargement of the thyroid gland was shown in 64% of our patients, mostly with multinodular appearance, and in some with retrosternal invasion. Neurological complications were observed in 13 patients (59%). Four subjects, who carry two different TPO mutations, had sensorineural deafness. Two previously described TPO gene mutations [G1567A (G493S) and C1708T (R540X)] and one novel TPO gene mutation [C965T (S292F)] were identified. The two previously described mutations were present in 90% of the subjects. Haplotyping suggested a distant common ancestry for each of these two mutations.Conclusions  Three different TPO gene mutations were found to be responsible for IOD in a consanguineous Israeli population. The high rate of development of multinodular glands (MNGs) in our cohort of patients indicates the need for long‐term follow‐up of patients with TPO gene mutations.
Thyroid function in paediatric and young adult patients after sarcoma therapy: a report from the Late Effects Surveillance System
Authors: Paulides M. , Dörr H. G. , Stöhr W. , Bielack S. , Koscielniak E. , Klingebiel T. , Jürgens H. , Bölling T. , Willich N. , Sauer R. , Langer T. , Beck J. D. 
Published: March 2007

SummaryObjective  The role of chemotherapy in thyroid sequelae after cancer treatment has not been studied systematically, especially in sarcoma patients. The aim of this study was to determine the incidence of post‐therapeutic thyroid disorders and their contributing factors in a cohort of paediatric sarcoma patients.Design  Late effects of sarcoma treatment have been collected prospectively within the Late Effects Surveillance System (LESS) in Germany, Austria and Switzerland since 1998.Patients  We studied 340 relapse‐free paediatric patients (median age at diagnosis 12·2 [interquartile range (IQR) = 7·3–15·6 years] treated for osteosarcoma, soft tissue sarcoma or Ewing's sarcoma within the COSS‐96, CWS‐96/CWS‐2002P or EICESS‐92/EURO‐E.W.I.N.G.‐99 therapy trials. In addition to polychemotherapy, 127 patients were irradiated (mean cumulative dose 47 ± 9·7 Gy), including 51 patients with irradiation to the head/neck region. Median follow‐up was 24·6 (IQR = 11·9–44·9) months.Measurements  We reviewed the results of yearly examinations of serum TSH and fT4 levels and thyroid ultrasound examinations.Results  The incidence of thyroid disorders was 37% (19/51, 95% CI 24–52%) in patients with head/neck irradiation, and 11% (32/289, 95% CI 8–15%) in patients without irradiation to the head/neck. Thyroid disorders were more frequent in patients treated with idarubicin (P = 0·027) and trofosfamide (P = 0·016). We also found a significant association between raised TSH levels and treatment with trofosfamide (P = 0·008) or idarubicin (P = 0·037) (n = 250).Conclusions  The incidence of thyroid disorders in the head/neck‐irradiated group was high. Even without head/neck irradiation, we found an increased proportion of patients with thyroid disorders, possibly as a result of chemotherapy.
Low prevalence of hypothyroidism among black and Mulatto people in a population‐based study of Brazilian women
Authors: Sichieri Rosely , Baima Jader , Marante Tatiana , De Vasconcellos Mauricio Teixeira Leite , Moura Anibal Sanchez , Vaisman Mario 
Published: March 2007

SummaryObjective  African‐Americans have been shown to have low prevalence of hypothyroidism. Brazil has a high ethnic admixture allowing further exploration into whether environmental factors can explain the ethnic differences.Design  A survey, representative of the population of Rio de Janeiro, a large metropolitan city in Brazil. Factors studied included race, parity, income, schooling, and smoking.Population  The survey was carried out in Rio de Janeiro whereby households (1500) were selected using three‐stage probability sampling. A total of 1298 (86·5%) women participated in the survey (non‐response: 13·5%).Measurements  TSH from blood drawn at the households. Anti‐thyroperoxidase (anti‐TPO) antibodies and free T4 were also measured.Results  Overall prevalence of hypothyroidism (TSH > 4 mUI/ml or taking medication) was 12·3%. Prevalence was 6·9% in black people, 8·8% in Mulatto people, and 16·7% among white people. The mean serum TSH of the population was 2·65 (95% confidence interval 2·33–2·97). The TSH distribution of black and Mulatto people was shifted to the left compared to white people. After adjustment for age, income, smoking and presence of anti‐TPO, Black and Mulatto people were still protected from hypothyroidism. The adjusted odds ratio for black compared to white people was 0·45 (95% CI 0·30–0·68) and for Mulatto people was 0·34 (95% CI 0·18–0·63). Serum TSH levels were significantly lower in smokers than in non‐smokers, but there was no association between number of cigarettes smoked and serum TSH level.Conclusions  This is the first time it has been demonstrated that Mulatto people have a prevalence of hypothyroidism which lies between that of white and black people, independent of the prevalence of anti‐TPO and smoking.
Effects of habitat complexity on community structure and predator avoidance behaviour of littoral zooplankton in temperate versus subtropical shallow lakes
Authors: MEERHOFF MARIANA , IGLESIAS CARLOS , DE MELLO FRANCO TEIXEIRA , CLEMENTE JUAN M. , JENSEN ELISABETH , LAURIDSEN TORBEN L. , JEPPESEN ERIK 
Published: March 2007

Summary1. Structural complexity may stabilise predator–prey interactions and affect the outcome of trophic cascades by providing prey refuges. In deep lakes, vulnerable zooplankton move vertically to avoid fish predation. In contrast, submerged plants often provide a diel refuge against fish predation for large‐bodied zooplankton in shallow temperate lakes, with consequences for the whole ecosystem.2. To test the extent to which macrophytes serve as refuges for zooplankton in temperate and subtropical lakes, we introduced artificial plant beds into the littoral area of five pairs of shallow lakes in Uruguay (30°–35°S) and Denmark (55°–57°N). We used plants of different architecture (submerged and free‐floating) along a gradient of turbidity over which the lakes were paired.3. We found remarkable differences in the structure (taxon‐richness at the genus level, composition and density) of the zooplankton communities in the littoral area between climate zones. Richer communities of larger‐bodied taxa (frequently including Daphnia spp.) occurred in the temperate lakes, whereas small‐bodied taxa characterised the subtropical lakes. More genera and a higher density of benthic/plant‐associated cladocerans also occurred in the temperate lakes. The density of all crustaceans, except calanoid copepods, was significantly higher in the temperate lakes (c. 5.5‐fold higher).4. Fish and shrimps (genus Palaemonetes) seemed to exert a stronger predation pressure on zooplankton in the plant beds in the subtropical lakes, while the pelagic invertebrate Chaoborus sp. was slightly more abundant than in the temperate lakes. In contrast, plant‐associated predatory macroinvertebrates were eight times more abundant in the temperate than in the subtropical lakes.5. The artificial submerged plants hosted significantly more cladocerans than the free‐floating plants, which were particularly avoided in the subtropical lakes. Patterns indicating diel horizontal migration were frequently observed for both overall zooplankton density and individual taxa in the temperate, but not the subtropical, lakes. In contrast, patterns of diel vertical migration prevailed for both the overall zooplankton and for most individual taxa in the subtropics, irrespective of water turbidity.6. Higher fish predation probably shapes the general structure and dynamics of cladoceran communities in the subtropical lakes. Our results support the hypothesis that horizontal migration is less prevalent in the subtropics than in temperate lakes, and that no predator‐avoidance behaviour effectively counteracts predation pressure in the subtropics. Positive effects of aquatic plants on water transparency, via their acting as a refuge for zooplankton, may be generally weak or rare in warm lakes.
Sexual reproduction and diapause ofHexarthrasp. (Rotifera) in short‐lived ponds in the Chihuahuan Desert
Authors: SCHRÖDER T. , HOWARD S. , ARROYO M. L. , WALSH E. J. 
Published: March 2007

Summary1. In the life cycle of monogonont rotifers it is generally assumed that diapausing eggs invariably hatch into amictic stem females which produce female offspring parthenogenetically. Diapausing eggs are only produced by later generations after sexual reproduction has been induced by environmental cues.2. We show that populations of an undescribedHexarthraspecies inhabiting small temporary ponds in the Chihuahuan Desert deviate from this life cycle pattern. These ponds may dry within days and up to 85% of females were mictic. Females producing male offspring and diapausing eggs were observed 1 or 2 days, respectively, after ponds had filled with water.3. Under laboratory conditions, 7–46% of females hatching from re‐hydrated sediments were sexual. Male offspring of these females can fertilise other mictic stem females leading to diapausing egg formation. In laboratory experiments, females produced fully developed diapausing eggs within 1.9 days at 20 °C and 1.2 days at 30 °C.4. In addition, embryonic development time (1.1–0.3 days at temperatures between 12 and 30 °C) and juvenile period (2.1–0.5 days for the same temperature range) are shorter than those of other rotifer species. In short‐lived habitats, the potential for rapid population development and production of new diapausing eggs may be crucial in the long‐term survival of populations.
A light regulated OmpR‐class promoter element co‐ordinates light‐harvesting protein and chromophore biosynthetic enzyme gene expression
Authors: Alvey Richard M. , Bezy Ryan P. , Frankenberg‐Dinkel Nicole , Kehoe David M. 
Published: March 2007

SummaryCo‐ordination of chromophore and apoprotein biosynthesis is required during photosynthetic light‐harvesting antennae production, such as occurs during complementary chromatic adaptation (CCA). This response to ambient light colour changes is controlled by a phytochrome‐class photoreceptor and involves changes in the synthesis of cyanobacterial light‐harvesting antennae. During growth in red light, CCA activates cpc2 transcription, an operon that encodes the light‐harvesting protein phycocyanin. In order to function, this apoprotein must have covalently attached phycocyanobilin chromophores, which are synthesized by PcyA. We show that pcyA is also transcriptionally activated by CCA during red light growth and is not regulated via feedback that senses cpc2 RNA levels. The pcyA and cpc2 promoters contain a common regulatory element, a direct repeat typical of OmpR‐class transcription factor binding sites, at similar positions relative to their red light‐controlled transcription start sites. Deletion of this element from the pcyA promoter eliminated CCA‐regulated transcription, and insertion of the element into a non‐light responsive promoter conferred CCA regulation. We conclude that this element is necessary and sufficient to confer CCA transcriptional regulation and that it co‐ordinates phycocyanin and phycocyanobilin biosynthesis in red light.
Recognition of the N‐terminal lectin domain of FimH adhesin by the usher FimD is required for type 1 pilus biogenesis
Authors: Munera Diana , Hultgren Scott , Fernández Luis Ángel 
Published: March 2007

SummaryIn this work we discover that a specific recognition of the N‐terminal lectin domain of FimH adhesin by the usher FimD is essential for the biogenesis of type 1 pili in Escherichia coli. These filamentous organelles are assembled by the chaperone–usher pathway, in which binary complexes between fimbrial subunits and the periplasmic chaperone FimC are recognized by the outer membrane protein FimD (the usher). FimH adhesin initiates fimbriae polymerization and is the first subunit incorporated in the filament. Accordingly, FimD shows higher affinity for the FimC/FimH complex although the structural basis of this specificity is unknown. We have analysed the assembly into fimbria, and the interaction with FimD in vivo, of FimH variants in which the N‐terminal lectin domain of FimH was deleted or substituted by different immunoglobulin (Ig) domains, or in which these Ig domains were fused to the N‐terminus of full‐length FimH. From these data, along with the analysis of a FimH mutant with a single amino acid change (G16D) in the N‐terminal lectin domain, we conclude that the lectin domain of FimH is recognized by FimD usher as an essential step for type 1 pilus biogenesis.
Metabolism of glutamine and glutathione via γ‐glutamyltranspeptidase and glutamate transport in Helicobacter pylori: possible significance in the pathophysiology of the organism
Authors: Shibayama Keigo , Wachino Jun‐ichi , Arakawa Yoshichika , Saidijam Massoud , Rutherford Nicholas G. , Henderson Peter J. F. 
Published: March 2007

Summaryγ‐Glutamyltranspeptidase (GGT) is a periplasmic enzyme of Helicobacter pylori implicated in its pathogenesis towards mammalian cells. We have cloned and expressed the H. pylori strain 26695 recombinant GGT protein in Escherichia coli and purified it to homogeneity. The purified protein exhibited hydrolysis activity with very high affinities for glutamine and glutathione shown by apparent Km values lower than 1 μM. H. pylori cells were unable to take up extracellular glutamine and glutathione directly. Instead, these substances were hydrolysed to glutamate by the action of GGT outside the cells. The glutamate produced was then transported by a Na+‐dependent reaction into H. pylori cells, where it was mainly incorporated into the TCA cycle and partially utilized as a substrate for glutamine synthesis. These observations show that one of the principle physiological functions of H. pylori GGT is to enable H. pylori cells to utilize extracellular glutamine and glutathione as a source of glutamate. As glutamine and glutathione are important nutrients for maintenance of healthy gastrointestinal tissue, their depletion by the GGT enzyme is hypothesized to account for the damaging of mammalian cells and the pathophysiology of H. pylori.
Xanthomonas campestris cell–cell communication involves a putative nucleotide receptor protein Clp and a hierarchical signalling network
Authors: He Ya‐Wen , Ng Alvin Yu‐Jin , Xu Min , Lin Kui , Wang Lian‐Hui , Dong Yi‐Hu , Zhang Lian‐Hui 
Published: March 2007

SummaryThe bacterial pathogen Xanthomonas campestris pv. campestris co‐ordinates virulence factor production and biofilm dispersal through a diffusible signal factor (DSF)‐mediated cell–cell communication mechanism. The RpfC/RpfG two‐component system plays a key role in DSF signal transduction and appears to modulate downstream DSF regulon by changing intracellular content of cyclic dimeric GMP (c‐di‐GMP), an unusual nucleotide second messenger. Here we show that Clp, a conserved global regulator showing a strong homology to the cAMP nucleotide receptor protein Crp of Escherichia coli, is essential for DSF regulation of virulence factor production but not for biofilm dispersal. Deletion of clp in Xcc changed the transcriptional expression of 299 genes including a few encoding transcription factors. Further genetic and microarray analysis led to identification of a homologue of the transcriptional regulator Zur, and a novel TetR‐type transcription factor FhrR. These two regulatory factors regulated different sets of genes within Clp regulon. These results outline a hierarchical signalling network by which DSF modulates different biological functions, and may also provide a clue on how the novel nucleotide signal can be coupled to its downstream regulatory networks.
Large‐scale deformation in the India‐Asia collision constrained by earthquakes and topography
Authors: Andronicos Christopher L. , Velasco Aaron A. , Hurtado José M. 
Published: March 2007

AbstractAnalysis of earthquake focal mechanisms allows division of the India‐Asia collision into kinematic domains that strongly correlate with topography. These kinematic domains indicate strain partitioning dominated by oblique slip deformation. The Kunlun and south Tibetan fault systems mark discontinuities in the strain field and bound the high, flat topography of the plateau which deforms by transtension. The northern and southern margins of Tibet deform by transpression or contraction and are topographically steep. Correlations between seismicity and topography are due to Mohr–Coulomb wedge mechanics at the northern and southern plateau margins which produce naturally steep surface slopes, whereas the flat interior and eastern margin of the Tibetan Plateau is underlain by viscous crust which supports subdued topography further muted by Cenozoic basin fill. These data indicate that the long wavelength topography of the India‐Asia collision is controlled by seismically caused surface displacements which are linked to deep crustal deformation mechanics.