bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Near-Infrared Raman Spectroscopy of Human Tissue with a Spectrograph and CCD Detector
Authors: Baraga Joseph J. , Feld Michael S. , Rava Richard P.
Published: June 2005

We demonstrate the use of a single-stage spectrograph and charge-coupled-device (CCD) detector to collect near-infrared (NIR) Raman spectra from intact human arterial tissue. With 810-nm excitation, the fluorescence emission from human artery is sufficiently weak to allow observation of Raman bands more rapidly with the spectrograph/CCD system than with 1064-nm excited FT-Raman systems. We also present a method for removing the broad-band emission from the spectra by computing the difference of two emission spectra collected at slightly different excitation frequencies. Our results indicate that NIR Raman spectra can be collected in under one second with the spectrograph/CCD system and an optical fiber probe, opening the possibility of in vivo clinical applications.
Infrared Study of Benzaldehyde and 4-Substituted Benzaldehydes in Carbon Tetrachloride and/or Chloroform Solutions: Aldehydic CH Group
Authors: Nyquist Richard A. , Settineri Sam E. , Luoma Davin A.
Published: June 2005

The vCH and 2 δCH Fermi resonance doublet and unperturbed vCH and unperturbed 2 δCH for 4- x-benzaldehydes increase in frequency as the mole % CHCl3/CCl4 increases. One portion of the vCH and 2 δCH Fermi doublet occurs in the region 2726–2746 cm−1 and the other portion of the Fermi doublet occurs in the region 2805–2845 cm−1. The unperturbed vCH for 4- x-benzaldehydes is assigned in the region 2760–2810 cm−1. Submaxima are also noted for 4- x-benzaldehydes in the region 2726–2810 cm−1 and these bands are assigned to combination tones. The vasym. NO2 mode occurs in the region 1533.60–1538.73 cm−1 and the vsym. NO2 mode occurs in the region 1344.07–1345.63 cm−1 for 4-nitrobenzalde-hyde in CHCl3/CCl4 solutions. The vsym. NO2 mode shifts to lower frequency by ∼4.8 cm−1, while the vsym. NO2 mode shifts to higher frequency by ∼1.6 cm−1 in going from CCl4 solution to CHCl3 solution. The vCN mode for 4-cyanobenzaldehyde increases in frequency in a nonlinear manner as the mole % CHCl3/CCl4 increases. The vOH mode for 4-hydroxybenzaldehyde decreases in frequency in essentially a linear manner as the mole % CHCl3/CCl4 increases. The δCH mode for 4- x-benzaldehydes increases in frequency as the mole % CHCl3/CCl4 increases; however, neither unperturbed vCH nor δCH correlates with Hammett σp values.
UV Resonance Raman Spectra of Bacillus Spores
Authors: Ghiamati E. , Manoharan R. , Nelson W. H. , Sperry J. F.
Published: June 2005

UV resonance Raman spectra of Bacillus cereus, Bacillus megaterium, and Bacillus subtilis endospores have been excited at 222.7,230.7,242.5, and 251.1 nm, and spectra have been compared with those of vegetative cells. The resonance Raman spectra of aqueous solutions of dipicolinic acid and calcium dipicolinate have been measured at the same wavelengths. Spectra of endospores and their corresponding germinated spores show only modest differences when excited at 222, 231, and 251 nm. However, very substantial differences appear when excitation occurs at 242 nm. Difference spectra obtained at 242 nm by subtracting spectra of germinated spores of Bacillus cereus from spectra of their corresponding endospores are attributed almost entirely to dipicolinate. Vegetative cells and endospores show large spectral dissimilarities at all exciting wavelengths. These spectral differences, which vary strongly with exciting wavelength, appear to be the result of large differences in the amounts and composition of proteins and nucleic acids, especially ribosomal RNA. The very substantial resonance enhancement of Raman spectra has been obtained from aqueous solutions of pure dipicolinic acid and of sodium and calcium dipicolinate salts, as well as spores at the various exciting wavelengths. The strong enhancement of dipicolinate spectra in spores, however, was noted only with 242-nm excitation. Consequently, only with 242-nm light was it possible to selectively and sensitively excite and study calcium dipicolinate in spores. Resonance enhancement of the dipicolinate spectra with 242-nm excitation appears due primarily to resonance interactions with n-π* electronic transitions associated with the pyridine ring and/or the carboxylate group.
Simultaneous GC-FT-IR/GC-MS Analysis for Isomer-Specific Identification and Quantitation of Complex Mixture Components
Authors: Smyrl N. R. , Hembree D. M. , Davis W. E. , Williams D. M. , Vance J. C.
Published: June 2005

The construction and capabilities of a new instrument combining infrared and mass spectrometry to simultaneously examine the effluent from a single capillary column gas chromatographic injection are described. Gas chromatography-mass spectrometry (GC-MS) is performed in the conventional manner. However, the Fourier transform infrared (FT-IR) portion of the instrument employs a new sampling method involving low-temperature trapping of the effluent from the gas chromatograph. The mass spectrometer was over two orders of magnitude more sensitive (161 fg detection limit for naphthalene) than the infrared (40 pg). The qualitative capabilities of infrared spectrometry, particularly when isomerspecific identifications are necessary, are shown to be highly complementary to the usual GC-MS method for analyzing complex mixtures
Suggestion for the Improvement of Camera-Ready Copy (CRC) Papers Submitted to Applied Spectroscopy
Authors: White Jeffrey S.
Published: June 2005

A suggestion for the improvement of the appearance of camera-ready copy is presented. The consistent use of higher-quality printers for the final printout of CRC articles submitted to Applied Spectroscopy is recommended.
Who Owns Native Culture?
Authors: Alexander Catherine
Published: June 2005

Who Owns Native Culture? Michael Brown (Cambridge, MA: Harvard University Press, 2004)
The Intimate Economies of Bangkok: Tomboys, Tycoons, and Avon Ladies in the Global City
Authors: Ferguson Jane M.
Published: June 2005

The Intimate Economies of Bangkok: Tomboys, Tycoons, and Avon Ladies in the Global City Ara Wilson (Berkeley: University of California Press, 2004)
Regulation of ghrelin secretion by somatostatin analogs in rats
Authors: Silva Antonio P , Bethmann Kerstin , Raulf Friedrich , Schmid Herbert A
Published: June 2005

Objective: Ghrelin is a hormone present in the plasma in two forms: octanoylated and des-octanoylated ghrelin. In pathophysiological conditions such as Prader–Willi syndrome and ghrelinoma, elevated ghrelin plasma levels are associated with pathological obesity. Clinical studies have shown that somatostatin downregulates ghrelin plasma levels in healthy volunteers. The aim of this study was to investigate the effects of two somatostatin analogues, SOM230 and octreotide, on ghrelin secretion in rats.

Methods: Ghrelin secretion was either unstimulated or stimulated by overnight fasting. Treatment with SOM230 and octreotide was either acute (s.c. injection 1 h before blood sampling) or prolonged (continuous s.c. infusion via 14-day osmotic minipumps).

Results: Acute treatment with octreotide dose-dependently inhibited unstimulated and stimulated secretion of total and active ghrelin. SOM230 (30 μg/kg) inhibited active ghrelin in fasted rats. Lower doses had no effect. After 7 days of treatment, active ghrelin was strongly inhibited by both compounds in fasted animals, with a stronger effect for octreotide. Lower inhibition was achieved in fed rats. After 14 days, the inhibition with octreotide in fasted rats was lower and SOM230 had no effect. Somatostatin receptor expression analysis in the rat glandular stomach revealed a predominant sst1 and sst2 expression, low expression of sst3 and sst4, and hardly detectable sst5 mRNA expression.

Conclusions: Somatostatin analogues may be useful for the inhibition of physiologically elevated ghrelin plasma levels. This inhibition appears to be mediated by sst2 receptors in the rat, and desensitizes after 14 days of treatment.
Adult height of prepubertal short children born small for gestational age treated with GH
Authors: Rosilio Myriam , Carel Jean-Claude , Ecosse Emmanuel , Chaussainon Jean-Louis , _ _
Published: June 2005

Objective: Human GH (hGH) treatment leads to catch-up growth in children with short stature born small for gestational age (SGA). However, long-term efficacy and safety results in this patient group remain scarce. The present study assessed the efficacy and safety of late childhood treatment with biosynthetic hGH (Humatrope) in a group of short children born SGA (height <−2 standard deviation scores (SDS)).

Design: Patients in this open-label, Phase III, multicenter study received a daily hGH dose of 0.067 mg/kg for 2 years, and then received no treatment for the following 2 years. After the fourth year on study, patients whose height had decreased more than 0.5 SDS but who still showed growth potential based on bone age were allowed to resume treatment until they reached adult height.

Methods: Height gain SDS was assessed for 11 girls and 24 boys (mean age±s.d. 9.6±0.9 years) at the end of the 2 years of hGH treatment, during the subsequent 2-year off-treatment period, and upon reaching adult height.

Results: At the end of the initial 2-year treatment period, 83% of patients had reached a height within the normal range, with a mean increase in height SDS vs baseline of 1.3±0.3 (P <0.001). Adult heights (n = 20) were within the normal range for 50% of patients, and mean height gain from baseline was statistically significant (0.7±0.8 SDS, P <0.001). Fasting glucose and glycosylated hemoglobin levels were not significantly modified during treatment.

Conclusions: High-dose hGH treatment for a minimum of 2 years in short children born SGA was well tolerated and resulted in a significant increase in adolescent and adult height.
Mutation analysis of the MCHR1 gene in human obesity
Authors: Wermter Anne-Kathrin , Reichwald Kathrin , Büch Thomas , Geller Frank , Platzer Cornelia , Huse Klaus , Hess Claudia , Remschmidt Helmut , Gudermann Thomas , Preibisch Gerald , Siegfried Wolfgang , Goldschmidt Hans-Peter , Li Wei-Dong , Price R Arlen , Biebermann Heike , Krude Heiko , Vollmert Caren , Wichmann H-Erich , Illig Thomas , Sørensen Thorkild I A , Astrup Arne , Larsen Lesli Hingstrup , Pedersen Oluf , Eberlé Delphine , Clément Karine , Blundell John , Wabitsch Martin , Schäfer Helmut , Platzer Matthias , Hinney Anke , Hebebrand Johannes
Published: June 2005

Objective: The importance of the melanin-concentrating hormone (MCH) system for regulation of energy homeostasis and body weight has been demonstrated in rodents. We analysed the human MCH receptor 1 gene (MCHR1) with respect to human obesity.

Design: This consisted of genomic screening of 13.4 kb encompassing theMCHR1in extremely obese German children and adolescents and association analyses for two coding single nucleotide polymorphisms (SNPs). To confirm initial positive association results, additional association studies and transmission disequilibrium tests in further German, Danish, French and American samples were conducted. Selected SNPs were investigated using functionalin vitrostudies and reporter gene assays.

Methods: Single-stranded conformation polymorphism analysis, re-sequencing, PCR-restriction fragment length polymorphism analyses, tetra-primer amplification refractory mutation systems, matrix-assisted laser desorption/ionization time of flight mass spectrometry and reporter gene assays were carried out as well as measuring inositol phosphate formation, inhibition of cAMP formation and activation of p42/44 MAP kinase.

Results: We identified 11 infrequent variations and two SNPs in theMCHR1coding sequence and 18 SNPs (eight novel) in the flanking sequence. Association and transmission disequilibrium with obesity were detected for several SNPs in independent study groups of German obese children and adolescents and controls. In two German samples, encompassing 4056 and 295 individuals, trends towards association with obesity were detected. Findings in a second epidemiological German sample and in Danish, French and American samples were negative. Functionalin vitrostudies as well as reporter gene assays revealed no significant results.

Conclusion: Our initial association ofMCHR1alleles/haplotype detected might be related to juvenile-onset obesity, conditional on a particular genetic and/or environmental background. Alternatively, we could not exclude the possibility that the initially detected association represented a false positive finding.
Sympatho-vagal control of heart rate variability in patients treated with suppressive doses of L-thyroxine for thyroid cancer
Authors: Casu Massimo , Cappi Caterina , Patrone Vittoriana , Repetto Eva , Giusti Massimo , Minuto Francesco , Murialdo Giovanni
Published: June 2005

Objective: This study aimed to analyze the autonomic control of heart rate variability (HRV) in subjects receiving chronic l-thyroxine (l-T4) treatment after total thyroidectomy and 131I therapy for differentiated thyroid carcinoma.

Methods: Blood pressure (BP) and sympatho-vagal activity (evaluated by power spectral analysis (PSA) of time-domain parameters of HRV) were studied in clinostatism and after orthostatism in 24 healthy controls, and in 12 patients taking l-T4 (125–200 μg/day) to maintain serum TSH levels at <0.01 μIU/ml. The study of HRV by PSA is a non-invasive method of analyzing sympatho-vagal control of HRV by quantifying high-frequency (HF) (0.15–0.4 Hz) and low-frequency (LF) (0.04–0.15 Hz) powers.

Results: Patients on L-T4 treatment had undetectable TSH levels, serum free T4 (fT4) above the normal range or at the upper limit in one case, and normal free tri-iodothyronine (fT3) levels. Heart rate and R–R intervals were not different in the two groups, both in clinostatism and in ortostatism. Systolic and mean BP were higher in patients than in controls and were inversely correlated with actual serum fT4 levels. During clinostatism, thyroid patients showed significantly lower LF power (P = 0.035), LF/(LF + HF) (P = 0.008) and LF/HF (P = 0.01) than controls. When patients moved from lying to standing, there was a significantly different decrease in orthostatic LF power (P = 0.001), LF/(LF + HF) (P = 0.044) and LF/HF (P = 0.047) versus controls.

Conclusions: Changes in autonomic control of HRV, characterized by decreased sympathetic activity and impaired sympatho-vagal balance with preserved vagal tone, are detectable in patients with hyperthyroxinemia due to suppressive l-T4 therapy and increased systolic and mean, but not diastolic, BP.
Spontaneous 24-h ghrelin secretion pattern in fasting subjects: maintenance of a meal-related pattern
Authors: Natalucci G , Riedl S , Gleiss A , Zidek T , Frisch H
Published: June 2005

Objective: Ghrelin stimulates GH release and causes weight gain through increased food intake and reduced fat utilization. Ghrelin levels were shown to rise in the preprandial period and decrease shortly after meal consumption, suggesting a role as a possible meal initiator. However, ghrelin secretion in fasting subjects has not yet been studied in detail.

Design: 24-h ghrelin profiles were studied in six healthy volunteers (three females; 25.5 years; body mass index 22.8 kg/m2) and compared with GH, insulin and glucose levels.

Methods: Blood samples were taken every 20 min during a 24-h fasting period and total ghrelin levels were measured by RIA using a polyclonal rabbit antibody. The circadian pattern of ghrelin secretion and pulsatility (Cluster analysis) were evaluated.

Results: An increase and spontaneous decrease in ghrelin were seen at the timepoints of customary meals. Ghrelin was secreted in a pulsatile manner with approximately 8 peaks/24 h. An overall decrease in ghrelin levels was observed during the study period. There was no correlation of ghrelin with GH, insulin or blood glucose levels.

Conclusions: This pilot study indicates that fasting ghrelin profiles display a circadian pattern similar to that described in people eating three times per day. In a fasting condition, GH, insulin and glucose do not appear to be involved in ghrelin regulation. In addition, we found that ghrelin is secreted in a pulsatile pattern. The variation in ghrelin independently of meals in fasting subjects supports previous observations that it is the brain that is primarily involved in the regulation of meal initiation.
Factors influencing cure by transsphenoidal selective adenomectomy in paediatric Cushing’s disease
Authors: Storr Helen L , Afshar Farhad , Matson Matthew , Sabin Ian , Davies Kate M , Evanson Jane , Plowman P Nicholas , Besser G Michael , Monson John P , Grossman Ashley B , Savage Martin O
Published: June 2005

Objective: Early diagnosis and effective treatment of paediatric Cushing’s disease (CD) is necessary to minimise associated morbidity. Accepted first-line treatment is selective transsphenoidal microadenomectomy (TSS), which can be technically difficult, and cure rates vary considerably between centres. In our paediatric CD patient group we have assessed the possible factors which may influence cure by TSS.

Subjects and methods: From 1983–2004, 27 paediatric patients (16 males, 11 females; mean age±s.d., 13.1±3.2 yr; range, 6.4–17.8 yr) with CD were managed in our centre and underwent TSS. Sixteen patients (59%), seven males and nine females (mean age±s.d., 14.2±2.5 yr; range, 8.2–17.8 yr), were cured (post-operative serum cortisol < 50 nM). Eleven patients, nine males and two females (mean age±s.d., 11.5±3.6 yr; range, 6.4–17.8 yr) had post-operative cortisol levels above 50 nM (2–20 days), with mean serum cortisol levels at 09:00 h of 537 nM (range 269–900 nM) indicating a lack of cure. These 11 patients received external beam pituitary radiotherapy (RT). One patient with a pituitary macroadenoma had a post-operative cortisol level of < 50 nM but 0.8 yr later showed an elevated cortisol and residual disease.

Results: The patients cured by TSS alone were significantly older than those not cured (P = 0.038; Student’s t test). All patients had CT/MRI pituitary imaging: 14 were reported to have microadenomas and one macroadenoma, while 12 were reported as normal. Bilateral simultaneous inferior petrosal sinus sampling (BSIPSS) with i.v. corticotropin-releasing hormone (CRH) administration was introduced as a pre-operative investigation in 1986 and was performed in 21 patients (78%), on BSIPSS, 16 (76%) had evidence suggesting pituitary adrenocorticotropic hormone (ACTH) secretion (central to peripheral (IPS:P) ACTH ratio after CRH of ≥ 3.0) and 16 (76%) showed lateralisation of ACTH secretion (IPSG of ≥ 1.4). There was concordance between the BSIPSS finding and the position of the microadenoma at surgery in 17/21 (81%) patients. Of the 16 patients showing lateralisation of ACTH secretion, 12 (75%) were cured by TSS. Of the four without lateralisation of ACTH, suggesting a midline lesion, 3 (75%) were cured by TSS. Post-operative pituitary hormone deficiencies in the patients cured by TSS were: pan-hypopituitarism 1/16, isolated growth hormone deficiency (GHD) (peak GH on glucagon/ITT < 1–17.9 mU/l) 9/16 and diabetes insipidus 3/16.

Conclusion: Over a 21-year period selective adenomectomy by TSS cured 59% of all paediatric CD patients, with higher age favouring cure. Introduction of BSIPSS resulted in the demonstration of a high rate of lateralisation of ACTH secretion consistent with the surgical identification of the adenoma, and therefore appears likely to have contributed to the higher surgical cure rate.
Isoenzyme type 1 of 5alpha-reductase is abundantly transcribed in normal human genital skin fibroblasts and may play an important role in masculinization of 5alpha-reductase type 2 deficient males
Authors: Thiele Susanne , Hoppe Ute , Holterhus Paul-Martin , Hiort Olaf
Published: June 2005

Objective: 5alpha-reductase enzymes reduce testosterone (T) to the most potent androgen dihydrotestosterone (DHT). Two isoenzymes are known to day. While the type 2-enzyme (5RII) is predominantly expressed in male genital tissues and mutations are known to cause a severe virilization disorder in genetic males, the role of the type 1-enzyme (5RI) in normal male androgen physiology is unclear. We investigated whether 5RI is transcribed in normal male genital skin fibroblasts (GSFs) and if the transcription is regulated by age or by androgens themselves.

Methods: GSF from 14 normally virilized males of different ages, ranging from 8 months to 72 years, obtained at circumcision were cultured. Total RNA was isolated after incubation for 48 h with 100 nM T or without androgens. Each sample was amplified in triplicate by real-time PCR with porphobilinogen desaminase as a housekeeping gene used for semiquantification. Selected cultures were analyzed after incubation with 10 and 100 nM T and 1 and 100 nM DHT for 24, 48 and 120 h.

Results: 5RI was transcribed in all investigated samples with a 4.5-fold variability in the mRNA concentration of different individuals. However, neither age-related regulation nor significant influence of T or DHT on the transcription rate was discovered.

Conclusion: Since 5RI is abundantly transcribed in GSFs, we hypothesize that this isoenzyme may play important roles in the androgen physiology of normally virilized males and may contribute to masculinization in 5RII-deficient males at the time of puberty.
The secretion and effect of inhibin A, activin A and follistatin on first-trimester trophoblasts in vitro
Authors: Bearfield C , Jauniaux E , Groome N , Sargent I L , Muttukrishna S
Published: June 2005

Objective: The objectives of this study were to investigate the effect of activin A and follistatin on first-trimester cytotrophoblast invasion in culture and to study the secretion of inhibin A, activin A and follistatin by these cellsin vitro.

Design and methods: Cytotrophoblasts were isolated from human placental chorionic villous tissue obtained from 6–8, 8–10 and 10–12 weeks gestation. Cells were cultured for 3 days on cell-culture inserts coated with gelatine for invasion studies and in 24-well culture plates for secretion studies. The effects of activin A (10 ng/ml), follistatin (100 ng/ml), interleukin 1β (IL-1β; 10 ng/ml) and epidermal growth factor (EGF; 10 ng/ml) on cytotrophoblast invasion were investigated using a non-radioactive invasion assay. Secretion of inhibin A, activin A and follistatin in the presence of EGF, IL-1β, activin A and follistatin were measured using in-house ELISAs.

Results and conclusion: Activin A, follistatin and EGF had a significant stimulatory effect on cytotrophoblast invasion from 6–10 weeks gestation. IL-1β had a significant stimulatory effect at 8–10 weeks and a significant inhibitory effect on invasion at 10–12 weeks gestation. Follistatin also had a significant inhibitory effect on invasion at 10–12 weeks gestation. In the secretion study, activin A secretion at 8–10 weeks was significantly stimulated by IL-1β and EGF. At 10–12 weeks, follistatin and EGF had a significant inhibitory effect on activin A secretion. Follistatin secretion was significantly increased in the presence of IL-1β at 6–8 weeks gestation. Inhibin A secretion was not significantly altered by EGF, IL-1β, activin A and follistatin. These results show that activin A promotes invasion of first-trimester cytotrophoblasts until 10 weeks gestation. There is a difference in the control of secretion of these proteins dependent on the gestation, suggesting that there is a tight regulation in the function of first-trimester trophoblasts depending on the gestational age.
Adding Confidence to Gene Expression Clustering
Authors: Munneke B , Schlauch K A , Simonsen K L , Beavis W D , Doerge R W
Published: June 2005

It has been well established that gene expression data contain large amounts of random variation that affects both the analysis and the results of microarray experiments. Typically, microarray data are either tested for differential expression between conditions or grouped on the basis of profiles that are assessed temporally or across genetic or environmental conditions. While testing differential expression relies on levels of certainty to evaluate the relative worth of various analyses, cluster analysis is exploratory in nature and has not had the benefit of any judgment of statistical inference. By using a novel dissimilarity function to ascertain gene expression clusters and conditional randomization of the data space to illuminate distinctions between statistically significant clusters of gene expression patterns, we aim to provide a level of confidence to inferred clusters of gene expression data. We apply both permutation and convex hull approaches for randomization of the data space and show that both methods can provide an effective assessment of gene expression profiles whose coregulation is statistically different from that expected by random chance alone.
DNA Sequence Polymorphism and Divergence at the erect wing and suppressor of sable Loci of Drosophila melanogaster and D. simulans
Authors: Braverman John M , Lazzaro Brian P , Aguadé Montserrat , Langley Charles H
Published: June 2005

Several evolutionary models of linked selection (e.g., genetic hitchhiking, background selection, and random environment) predict a reduction in polymorphism relative to divergence in genomic regions where the rate of crossing over per physical distance is restricted. We tested this prediction near the telomere of the Drosophila melanogaster and D. simulans X chromosome at two loci, erect wing (ewg) and suppressor of sable [su(s)]. Consistent with this prediction, polymorphism is reduced at both loci, while divergence is normal. The reduction is greater at ewg, the more distal of the two regions. Two models can be discriminated by comparing the observed site frequency spectra with those predicted by the models. The hitchhiking model predicts a skew toward rare variants in a sample, while the spectra under the background-selection model are similar to those of the neutral model of molecular evolution. Statistical tests of the fit to the predictions of these models require many sampled alleles and segregating sites. Thus we used SSCP and stratified DNA sequencing to cover a large number of randomly sampled alleles (∼50) from each of three populations. The result is a clear trend toward negative values of Tajima's D, indicating an excess of rare variants at ewg, the more distal of the two loci. One fixed difference among the populations and high FST values indicate strong population subdivision among the three populations at ewg. These results indicate genetic hitchhiking at ewg, in particular, geographically localized hitchhiking events within Africa. The reduction of polymorphism at su(s) combined with the excess of high-frequency variants in D. simulans is inconsistent with the hitchhiking and background-selection models.
The Heterotrimeric G-Protein GanB(α)-SfaD(β)-GpgA(γ) Is a Carbon Source Sensor Involved in Early cAMP-Dependent Germination inAspergillus nidulans
Authors: Lafon Anne , Seo Jeong-Ah , Han Kap-Hoon , Yu Jae-Hyuk , d'Enfert Christophe
Published: June 2005

The role of heterotrimeric G-proteins in cAMP-dependent germination of conidia was investigated in the filamentous ascomycete Aspergillus nidulans. We demonstrate that the Gα-subunit GanB mediates a rapid and transient activation of cAMP synthesis in response to glucose during the early period of germination. Moreover, deletion of individual G-protein subunits resulted in defective trehalose mobilization and altered germination kinetics, indicating that GanB(α)-SfaD(β)-GpgA(γ) constitutes a functional heterotrimer and controls cAMP/PKA signaling in response to glucose as well as conidial germination. Further genetic analyses suggest that GanB plays a primary role in cAMP/PKA signaling, whereas the SfaD-GpgA (Gβγ) heterodimer is crucial for proper activation of GanB signaling sensitized by glucose. In addition, the RGS protein RgsA is also involved in regulation of the cAMP/PKA pathway and germination via attenuation of GanB signaling. Genetic epistatic analyses led us to conclude that all controls exerted by GanB(α)-SfaD(β)-GpgA(γ) on conidial germination are mediated through the cAMP/PKA pathway. Furthermore, GanB may function in sensing various carbon sources and subsequent activation of downstream signaling for germination.
Construction of Linkage Maps in Full-Sib Families of Diploid Outbreeding Species by Minimizing the Number of Recombinations in Hidden Inheritance Vectors
Authors: Jansen J
Published: June 2005

This article investigates the construction of linkage maps by means of the reconstruction of hidden inheritance vectors. An inheritance vector provides a description of the origin of marker alleles in an individual in terms of a binary code indicating the grandparental origin of the alleles. The practical application that is considered is the full-sib family of a diploid outbreeding species. Essentially, map construction is considered as an optimization problem in which marker data are used as restrictions on hidden inheritance vectors. Simulated annealing, a form of combinatorial optimization, is used to minimize the number of recombinations between adjacent markers. The new algorithm is applied to simulated data as well as to practical data obtained from a cross between two apple cultivars. For the practical data, a detailed procedure for examining the reliability of individual markers and their positions on the map is presented. Extensions of the method for more complicated population structures are discussed.
The Impact of Using Related Individuals for Haplotype Reconstruction in Population Studies
Authors: Schouten Michael T , Williams Christopher K I , Haley Chris S
Published: June 2005

Recent studies have highlighted the dangers of using haplotypes reconstructed directly from population data for a fine-scale mapping analysis. Family data may help resolve ambiguity, yet can be costly to obtain. This study is concerned with the following question: How much family data (if any) should be used to facilitate haplotype reconstruction in a population study? We conduct a simulation study to evaluate how changes in family information can affect the accuracy of haplotype frequency estimates and phase reconstruction. To reconstruct haplotypes, we introduce an EM-based algorithm that can efficiently accommodate unrelated individuals, parent-child trios, and arbitrarily large half-sib pedigrees. Simulations are conducted for a diverse set of haplotype frequency distributions, all of which have been previously published in empirical studies. A wide variety of important results regarding the effectiveness of using pedigree data in a population study are presented in a coherent, unified framework. Insight into the different properties of the haplotype frequency distribution that can influence experimental design is provided. We show that a preliminary estimate of the haplotype frequency distribution can be valuable in large population studies with fixed resources.
Cross-Species Comparison of Drosophila Male Accessory Gland Protein Genes
Authors: Mueller J L , Ram K Ravi , McGraw L A , Bloch Qazi M C , Siggia E D , Clark A G , Aquadro C F , Wolfner M F
Published: June 2005

Drosophila melanogaster males transfer seminal fluid proteins along with sperm during mating. Among these proteins, ACPs (Accessory gland proteins) from the male's accessory gland induce behavioral, physiological, and life span reduction in mated females and mediate sperm storage and utilization. A previous evolutionary EST screen in D. simulans identified partial cDNAs for 57 new candidate ACPs. Here we report the annotation and confirmation of the corresponding Acp genes in D. melanogaster. Of 57 new candidate Acp genes previously reported in D. melanogaster, 34 conform to our more stringent criteria for encoding putative male accessory gland extracellular proteins, thus bringing the total number of ACPs identified to 52 (34 plus 18 previously identified). This comprehensive set of Acp genes allows us to dissect the patterns of evolutionary change in a suite of proteins from a single male-specific reproductive tissue. We used sequence-based analysis to examine codon bias, gene duplications, and levels of divergence (via dN/dS values and ortholog detection) of the 52 D. melanogaster ACPs in D. simulans, D. yakuba, and D. pseudoobscura. We show that 58% of the 52 D. melanogaster Acp genes are detectable in D. pseudoobscura. Sequence comparisons of ACPs shared and not shared between D. melanogaster and D. pseudoobscura show that there are separate classes undergoing distinctly dissimilar evolutionary dynamics.
Surface jumping in a harmonic model of trans‐octatetraene: Franck—condon factors and accepting vibrational modes in s1→S0 non‐vertical radiationless transition
Authors: Shem‐Tov Sharona , Segev Bilha
Published: June 2005

A phase‐space method for finding the accepting modes in a non‐vertical radiationless vibronic transition and for recognizing the final state with the largest Franck—Condon factor is applied to a harmonic model of the S1 → S0 relaxation in trans‐octatetraene. Input required for the analysis includes the energy gap between S1 and S0, normal mode frequencies, reduced masses, and eigenvectors (including the Duschinsky rotation matrix), and the molecule equilibrium configurations (bond lengths and angles) in S1 and S0. Some of these data are taken from published experimental results and some are calculated in this work. The energy gap of 0.132 au is much larger than the energy of a vertical transition, which is only 0.047 au. The phase‐space method gives a closed‐form analytic solution for how to divide the excess energy between the accepting modes. The final distribution includes a large excitation of the two CH2 end groups, where the motion of the two hydrogen atoms within each quasilocal CH2 group is antisymmetric; a symmetric stretch of the two central C‐H bonds of the molecule; and small totally symmetric bending of the whole molecule. Comparison of Franck‐Condon factors (exact within the harmonic model) of the final state obtained by the phase‐space analysis and of other similar isoenergetic states shows that the phase‐space method indeed chooses the most probable final energy distribution. Possible modifications of these results due to anharmonic effects are discussed.
Nonadiabatic vibronic dynamics as a tool. From surface nanochemistry to coherently driven molecular machines
Authors: Seideman Tamar
Published: June 2005

Resonances are ubiquitous in molecular heterojunctions and in scanning tunneling microscopy (STM) experiments. In the former environment, resonance tunneling is essential for favorable wire‐length‐dependence of the conductance and is often the mechanism underlying conductance enhancement through application of a gate voltage. In the latter environment, resonance tunneling has served to develop a powerful vibrational spectroscopy.

Resonance conductance is often strongly nonadiabatic; in the course of the tunneling event, electron energy is channelled into vibrational modes and triggers molecular dynamics. The qualitative physics underlying current‐driven, resonance‐mediated dynamics in molecular electronics is very simple, and is familiar from related phenomena such as gas phase electron‐molecule scattering and photochemistry on conducting surfaces. Equilibrium displacement between the initial and resonant states translates into vibronic coupling in the language of the Marcus theory of electron transfer; it produces a nonstationary superposition in the nuclear subspace that evolves during the resonance lifetime. Upon relaxation the system is internally excited and interesting dynamics is likely to ensue.

While the underlying physics is very general, the single‐molecule STM and molecular heterojunction environments open unique and exciting opportunities. The former introduces the possibility of determining resonance lifetimes through fit of experimental voltage dependencies to a quantum mechanical theory. The latter introduces the possibility of developing coherently driven molecular machines, a new form of nanolithography, and a new means of manipulating the conductivity of molecular‐scale devices.

We briefly review the theory of current‐driven dynamics in molecular‐scale devices, discuss the results of ongoing research on surface nanochemistry and molecular machines, and sketch a variety of potential applications.
Femtosecond dynamics of electron transfer, localization, and solvation processes at the ice—metal interface
Authors: Bovensiepen Uwe , Gahl Cornelius , Stähler Julia , Loukakos Panagiotis A. , Wolf Martin
Published: June 2005

The ultrafast dynamics of excess electrons in amorphous ice layers on single‐crystal metal surfaces are investigated by femtosecond time‐ and angle‐resolved two‐photon‐photoemission spectroscopy. Photoexcited electrons are injected from the metal substrate into delocalized states of the conduction band of ice and localize in the ice layer within 100 fs. Subsequently, energetic stabilization of this localized species is observed on a time scale of ∼1 ps, which is attributed to electron solvation by nonadiabatic coupling to nuclear degrees of freedom of the surrounding polar molecular environment. Concomitant with this stabilization process, residual wave function overlap of the solvated electron with the metal substrate results in back‐transfer by tunneling through the solvation shell. At such interfaces the correlation of electronic and molecular structure with the resulting solvation dynamics can be explored using different substrates as a template. Here we compare data on molecularly thin D2O ice layers grown on Cu(111) and Ru(001). On Ru(001) both the stabilization and back‐transfer proceed about three times faster compared to Cu(111), which is attributed to different interfacial structures and the role of d‐states, and projected band gaps in the electron transfer process.
Mechanisms of endocrine therapy-responsive and -unresponsive prostate tumours
Authors: Culig Z , Steiner H , Bartsch G , Hobisch A
Published: June 2005

Several options for the endocrine treatment of non-organ-confined prostate cancer are available. They include surgical or medical removal of androgenic hormones or administration of non-steroidal anti-androgens. However, tumour progression after a period of remission of the disease inevitably occurs in virtually all patients. The androgen receptor (AR) is, in various tumour models, implicated in the development of therapy resistance but molecular mechanisms that by-pass the receptor have also been described. Adaptation mechanisms relevant to tumour recurrence include up-regulation of AR mRNA and protein, overexpression of AR coactivators, increased activation of mutated receptors by steroids and anti-androgens, and ligand-independent activation. For research studies, sublines that respond to but do not depend on androgen for their proliferation were generated. Coactivators SRC-1, TIF-2, RAC3, p300, CBP, Tip60, and gelsolin are highly expressed in endocrine therapy-resistant prostate cancer. AR point mutations are increasingly detected in relapsed cancers and contribute to the failure of endocrine therapy in a subgroup of patients. Ligand-independent activation of the AR by HER-2/neu and interleukin-6 is associated with activation of the signalling pathway of mitogen-activated protein kinase. Increased activity of intracellular kinases may affect cellular events in both an AR-dependent and -independent manner. Mitogen-activated protein kinases are strongly phosphorylated in endocrine therapy-resistant prostate tumours. Similarly, activation of the AR by phosphorylated protein kinase B, Akt, has also been reported in prostate cancer. Activation of the Akt pathway contributes to increased survival of prostate tumour cells.
Developmental Antecedents of Cognitive Vulnerability to Depression: Review of Findings From the Cognitive Vulnerability to Depression Project
Authors: Alloy Lauren B. , Abramson Lyn Y. , Gibb Brandon E. , Crossfield Alisa G. , Pieracci Antonia M. , Spasojevic Jelena , Steinberg Jennifer A.
Published: June 2005

In this article, we review findings from the Temple-Wisconsin Cognitive Vulnerability to Depression (CVD) Project (Alloy & Abramson, 1999) regarding potential developmental antecedents of cognitive vulnerability to depression after first briefly summarizing the evidence from the project that negative cognitive styles, information processing, and rumination do, in fact, provide vulnerability to depression. Based on the project findings, we suggest that a continuum of negative emotional feedback, ranging from low emotional warmth/acceptance and negative inferential feedback at the milder end to emotional abuse at the more severe end, may play an important role in the development of cognitive vulnerability to depression and depression itself.
Stability and Change of Sociotropy and Autonomy Subscales in Cognitive Therapy of Depression
Authors: Bieling Peter J. , Beck Aaron T. , Brown Gregory K.
Published: June 2005

Sociotropy and autonomy have been demonstrated to be a diathesis for depression as well as predictors of treatment outcome. There are few studies, however, that have investigated whether these vulnerability factors change with cognitive therapy (CT) and are associated with outcome in CT. Also, it appears that the autonomy construct may have both positive and negative content and it is important to examine these two aspects of autonomy in treatment. In this study, depressed outpatients (N = 149) were followed from intake to the 12th session of CT. The treatment outcome variables included depression (Beck Depression Inventory), hopelessness (Beck Hopelessness Scale), and sociotropy and autonomy (Sociotropy-Autonomy Scale [SAS]). Using a repeated measures analysis, depression symptoms and hopelessness decreased significantly over time. Both subscales of sociotropy, preference for affiliation and fear of criticism and rejection, were positively associated with depression at intake, and decreased significantly over time in those who responded to treatment. However, independent goal attainment, one subscale of autonomy, increased significantly over sessions and was associated with treatment response. The second subscale of autonomy, sensitivity to others’ control, demonstrated no change. The results suggest that independent goal attainment may be an indicator of psychological health. Implications for future research using the SAS and its subscales in treatment and vulnerability research are described.
Valence Shell Charge Concentrations at Pentacoordinate d0Transition‐Metal Centers: Non‐VSEPR Structures of Me2NbCl3and Me3NbCl2
Authors: McGrady G. Sean , Haaland Arne , Verne Hans Peter , Volden Hans Vidar , Downs Anthony J. , Shorokhov Dmitry , Eickerling Georg , Scherer Wolfgang
Published: June 2005

The molecular structures of the monomeric, pentacoordinated methylchloroniobium(IV) compounds Me3NbCl2and Me2NbCl3have been determined by gas electron diffraction (GED) and density functional theory (DFT) calculations, and, for Me3NbCl2, by single crystal X‐ray diffraction. Each of the molecules is found to have a heavy‐atom skeleton in the form of a trigonal bipyramid (TBP) with Cl atoms in the axial positions, in accord with their vibrational spectra. The TBP is somewhat distorted in the case of Me2NbCl3with the two axial NbCl bonds bentawayfrom the equatorial, slightly shorter NbCl bond. In the case of Me3NbCl2, moreover, the X‐ray model suggests structural distortions away from the idealizedC3hgeometry, in line with the results of quantum chemical calculations. Structure optimizations by DFT calculations and least‐squares refinement to the GED data yield the following structural parameters (calcd/exptl; eq=equatorial; ax=axial; distances in Å, angles in degrees; average values in 〈〉 brackets): Me3NbCl2, inC3vsymmetry, NbCl 〈2.370〉/〈2.319(3)〉, NbC 2.173/2.152(4), CH 〈1.096〉/1.124(5), ∢NbCH 〈109.3〉/105.2(8), ∢ClNbC 92.2/93.3(2), ∢CNbC 119.9/119.7(1); Me2NbCl3, inC2vsymmetry, NbClax2.361/2.304(5), NbCleq2.321/2.288(9), NbC 2.180/2.135(9), CH 〈1.094〉/1.12(1), ∢ClaxNbCleq98.5/96.5(6), ∢CNbC 121.0/114(2), ∢NbCH 〈108.9〉/109(2). The electronic structures of Me2NbCl3and Me3NbCl2have been explored by rigorous analysis of both the wavefunction and the topology of the electron density, employing DFT calculations. Hence the structures of these compounds are shown to reflect repulsion between the NbC and NbCl bonding electron density and charge concentrations induced by the methyl ligands in the valence shell of the Nb atom and arising mainly from use of Nb(4d) functions in the NbC bonds.
Structure and Bonding of Zinc Antimonides: Complex Frameworks and Narrow Band Gaps
Authors: Mikhaylushkin Arkady S. , Nylén Johanna , Häussermann Ulrich
Published: June 2005

We investigated crystal structure relationships, phase stability and chemical bonding of the thermoelectric materials ZnSb, α‐Zn4Sb3, and β‐Zn4Sb3 by means of first principles calculations. The structures of these materials are difficult to rationalise. This is especially true for β‐Zn4Sb3 because of the presence of vacancies and interstitial atoms. We recognised rhomboid rings Zn2Sb2 as central structural building units present in all materials. Importantly, these rings enable to establish a clear relationship between disordered β‐Zn4Sb3 and ordered low‐temperature α‐Zn4Sb3. Concerning the phase stability of Zn4Sb3 we identified a peculiar situation: α‐Zn4Sb3 is metastable and β‐Zn4Sb3 can only be thermodynamically stable when its structural disorder accounts for a large entropy contribution to free energy. According to their electronic structure zinc antimonides represent heteroatomic framework structures with a modest polarity. The peculiar electronic structure of Zn/Sb systems can also be modelled by Al/Si systems. The high coordination numbers in the frameworks implies the presence of multicentre bonding. We developed a simple bonding picture for these frameworks where multicentre bonding is confined to rhomboid rings Zn2Sb2.
Solution‐ and Solid‐Phase Synthesis of Radicicol (Monorden) and Pochonin C
Authors: Barluenga Sofia , Moulin Emilie , Lopez Pilar , Winssinger Nicolas
Published: June 2005

A modular synthesis for pochonin C and radicicol is reported. The two natural products were prepared in seven and eight steps, respectively, from three readily available fragments. Alternative syntheses of these compounds were achieved using a combination of polymer‐bound reagents and solid phase reactions. The conformation of the two natural products was studied and compared by using 2D NMR spectroscopy.
Cervimycin A–D: A Polyketide Glycoside Complex from a Cave Bacterium Can Defeat Vancomycin Resistance
Authors: Herold Kerstin , Gollmick Friedrich A. , Groth Ingrid , Roth Martin , Menzel Klaus‐Dieter , Möllmann Ute , Gräfe Udo , Hertweck Christian
Published: June 2005

Cervimycins A–D are novel polyketide glycosides with significant activity against multi‐drug‐resistant staphylococci and vancomycin‐resistant enterococci. They are produced by a strain of Streptomyces tendae, isolated from an ancient cave. The structures of the cervimycins were determined by performing extensive NMR and chemical degradation studies. All cervimycins have a common tetracyclic polyketide core that is substituted with unusual di‐ and tetrasaccharide chains, composed exclusively of trideoxysugars; however, they differ in the acetyl and carbamoyl ring substituent and in the highly unusual terminal methylmalonyl and dimethylmalonyl residues.
A polynomial algorithm for solving a general max‐min fairness problem
Authors: Tomaszewski Artur
Published: June 2005

An iterative algorithm of polynomial complexity is presented that solves a max‐min fairness problem which is often encountered while dealing with traffic routing or capacity allocation problems. The algorithm does not depend on any specific traffic routing problem formulation and is sufficiently general to be applied to a broad class of traffic routing and capacity allocation problems. The correctness of the algorithm and its complexity are formally proved. Copyright © 2005 AEIT.