bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chitinase-Like Protein CTL1 Plays a Role in Altering Root System Architecture in Response to Multiple Environmental Conditions
Authors: Hermans Christian , Porco Silvana , Verbruggen Nathalie , Bush Daniel R. 
Published: December 2009

AbstractPlant root architecture is highly responsive to changes in nutrient availability. However, the molecular mechanisms governing the adaptability of root systems to changing environmental conditions is poorly understood. A screen for abnormal root architecture responses to high nitrate in the growth medium was carried out for a population of ethyl methanesulfonate-mutagenized Arabidopsis (Arabidopsis thaliana). The growth and root architecture of the arm (for anion altered root morphology) mutant described here was similar to wild-type plants when grown on low to moderate nitrate concentrations, but on high nitrate, arm exhibited reduced primary root elongation, radial swelling, increased numbers of lateral roots, and increased root hair density when compared to the wild-type control. High concentrations of chloride and sucrose induced the same phenotype. In contrast, hypocotyl elongation in the dark was decreased independently of nitrate availability. Positional cloning identified a point mutation in the AtCTL1 gene that encodes a chitinase-related protein, although molecular and biochemical analysis showed that this protein does not possess chitinase enzymatic activity. CTL1 appears to play two roles in plant growth and development based on the constitutive effect of the arm mutation on primary root growth and its conditional impact on root architecture. We hypothesize that CTL1 plays a role in determining cell wall rigidity and that the activity is differentially regulated by pathways that are triggered by environmental conditions. Moreover, we show that mutants of some subunits of the cellulose synthase complex phenocopy the conditional effect on root architecture under nonpermissive conditions, suggesting they are also differentially regulated in response to a changing environment.
A Raf-Like MAPKKK Gene DSM1 Mediates Drought Resistance through Reactive Oxygen Species Scavenging in Rice
Authors: Ning Jing , Li Xianghua , Hicks Leslie M. , Xiong Lizhong 
Published: December 2009

Abstract
Mitogen-activated protein kinase (MAPK) cascades have been identified in various signaling pathways involved in plant development and stress responses. We identified a drought-hypersensitive mutant (drought-hypersensitive mutant1 [dsm1]) of a putative MAPK kinase kinase (MAPKKK) gene in rice (Oryza sativa). Two allelic dsm1 mutants were more sensitive than wild-type plants to drought stress at both seedling and panicle development stages. The dsm1 mutants lost water more rapidly than wild-type plants under drought stress, which was in agreement with the increased drought-sensitivity phenotype of the mutant plants. DSM1-RNA interference lines were also hypersensitive to drought stress. The predicted DSM1 protein belongs to a B3 subgroup of plant Raf-like MAPKKKs and was localized in the nucleus. By real-time PCR analysis, the DSM1 gene was induced by salt, drought, and abscisic acid, but not by cold. Microarray analysis revealed that two peroxidase (POX) genes, POX22.3 and POX8.1, were sharply down-regulated compared to wild type, suggesting that DSM1 may be involved in reactive oxygen species (ROS) signaling. Peroxidase activity, electrolyte leakage, chlorophyll content, and 3,3′-diaminobenzidine staining revealed that the dsm1 mutant was more sensitive to oxidative stress due to an increase in ROS damage caused by the reduced POX activity. Overexpression of DSM1 in rice increased the tolerance to dehydration stress at the seedling stage. Together, these results suggest that DSM1 might be a novel MAPKKK functioning as an early signaling component in regulating responses to drought stress by regulating scavenging of ROS in rice.
Translational pharmacokinetic–pharmacodynamic modelling; application to cardiovascular safety data for PF‐00821385, a novel HIV agent
Authors: Langdon Grant , Davis John D. , McFadyen Lynn M. , Dewhurst Mark , Brunton Neil S. , Rawal Jaiessh K. , Van der Graaf Piet H. , Benson Neil 
Published: December 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• While animal toxicology is routinely used for safety screening of compounds prior to their being tested in man, there is very little in the literature on the quantitative translation of cardiovascular drug effects from animal to man.WHAT THIS STUDY ADDS• This study compares pharmacokinetic–pharmacodynamic analysis of dog and human effects of PF‐00821385 on heart rate.• This paper considers how quantitative translational knowledge of drug effects in dogs may be used to optimize future human studies.AIMTo assess the translation of pharmacokinetic–pharmacodynamic (PK–PD) relationships for heart rate effects of PF‐00821385 in dog and man.METHODSCardiovascular telemetric parameters and concentration data were available for animals receiving active doses (0.5–120 mg kg−1,n= 4) or vehicle. PF‐00821385 was administered to 24 volunteers and pharmacokinetic and vital signs data were collected. PK–PD models were fitted using nonlinear mixed effects.RESULTSCompartmental models with linear absorption and clearance were used to describe pharmacokinetic disposition in animal and man. Diurnal variation in heart and pulse rate was best described with a single cosine function in both dog and man. Canine and human heart rate change were described by a linear model with free drug slope 1.76 bpm µM−1[95% confidence interval (CI) 1.17, 2.35] in the dog and 0.76 bpm µM−1(95% CI 0.54, 1.14) in man.CONCLUSIONSThe preclinical translational of concentration–response has been described and the potential for further interspecies extrapolation and optimization of clinical trial design is addressed.
Habitat‐related differences in the frequency selectivity of auditory filters in songbirds
Authors: Henry Kenneth S. , Lucas Jeffrey R. 
Published: December 2009

Summary 1. Environmental constraints in woodland habitats favour long‐range communication signals with slow modulations of frequency and amplitude, while constraints in open habitats favour faster modulations. 2. Spectral filtering by the peripheral auditory system results in a trade‐off between frequency resolution and temporal resolution of modulations. Greater frequency resolution requires integration of acoustic signals over a longer period of time, which in turn decreases responsiveness to temporal modulations. 3. Here, we test the hypothesis in songbirds that woodland habitats have selected for narrowly tuned auditory filters with high frequency resolution of tonal elements, while open habitats have selected for broader auditory filters with greater temporal resolution of rapid modulation. 4. Auditory filter shapes were measured at 2, 3 and 4 kHz in three woodland species, the dark‐eyed junco (Junco hyemalis), tufted titmouse (Baeolophus bicolor) and white‐breasted nuthatch (Sitta carolinensis), and two open‐habitat species, the house sparrow (Passer domesticus) and white‐crowned sparrow (Zonotrichia leucophrys). Auditory filter shapes were derived from auditory brainstem response thresholds in notched noise using Patterson’s rounded exponential (roex) auditory filter model. 5. Auditory filters increased in bandwidth with increasing frequency in all species except the dark‐eyed junco. Auditory filters were generally narrower in woodland species than open‐habitat species as predicted, although auditory filters of the junco were relatively narrow only at 4 kHz, and the difference between white‐crowned sparrows and tufted titmice was not significant. Finally, at 4 kHz, open‐habitat species had auditory filters with lower signal‐to‐noise response thresholds than woodland species (i.e. greater response efficiency). 6. The results suggest that environmental constraints on song structure have influenced the evolution of peripheral auditory filters in songbirds, although species using signals not optimized for long‐range transmission should be less affected. Differences in filter bandwidth between dark‐eyed juncos and white‐crowned sparrows are noteworthy because Junco and Zonotrichia share a recent common ancestor as sister genera within the Emberizidae. Finally, open‐habitat species may compensate for inherently lower sensitivity in noise of broad auditory filters with greater response efficiency.
A multi‐protein complex controls cAMP signalling and filamentation in the fungal pathogen Candida albicans
Authors: Hall Rebecca A. , Mühlschlegel Fritz A. 
Published: December 2009

Summary Candida albicans is an opportunistic fungal pathogen of humans. The ability of the fungus to grow as both yeast and filamentous forms is essential for its pathogenicity. Morphogenesis of C. albicans is largely regulated through the secondary messenger cAMP, produced by the soluble adenylyl cyclase, Cyr1p. Recent evidence suggests that Cyr1p can be directly stimulated by environmental cues to increase cytoplasmic cAMP levels and thus promote hyphal development. In this issue of Molecular Microbiology, Zou et al. demonstrate that, in response to some environmental cues, Cyr1p functions as part of a tripartite complex additionally involving Cap1p and G‐actin. All three proteins in the complex are required to raise cytosolic cAMP levels after stimulation with serum and bacterial peptidoglycan. The formation of such a complex highlights the importance of precise regulation of Cyr1p activity in response to host environmental cues.
Aquagenic acrokeratoderma
Authors: Luo Di‐Qing , Zhao Yu‐Kun , Zhang Wu‐Jun , Wu Liang‐Cai 
Published: December 2009

AbstractBackground  Aquagenic acrokeratoderma (AA) is a rare condition with female predilection that occurs after brief water exposure and disappears minutes to an hour after drying. The pathogenesis remains unclear.Methods  Four Chinese patients with AA were reported and analyzed.Results  There were 2 males and 2 females (age range: 14‐33 years) who presented with a 2‐week to more than 10‐year history of small white papules coalescing into edematous plaques on the hands; lesions appeared within 5‐10 minutes of water exposure, began to regress in 3–20 minutes and disappeared within 5 minutes to one hour after drying. Warm water provoked the lesions more rapidly than cold water. Lesions of a female patient could be triggered by detergent. In another female patient, lesions also involved the feet and were associated with palmoplantar erythema and hyperhidrosis. Biopsy from the lesion of one patient after water exposure revealed hyperkeratosis, mild hypergranulosis, and dilatated eccrine ducts. Biopsy from the lesion of another patient after drying showed normal epidermis and dermis. Two patients were treated with topical formalin 3% in alcohol, and two with 3% potassium aluminium sulfate solution with partial relief without any adverse effects.Conclusion  AA may occur in both males and females and may involve the feet. Warm water triggers the lesions more rapidly than cold. Topical formalin 3% in alcohol and 3% potassium aluminium sulfate solution may be optional therapy.
Respiratory disease in Niemann‐Pick type C2 is caused by pulmonary alveolar proteinosis
Authors: Griese M , Brasch F , Aldana VR , Cabrera MM , Goelnitz U , Ikonen E , Karam BJ , Liebisch G , Linder MD , Lohse P , Meyer W , Schmitz G , Pamir A , Ripper J , Rolfs A , Schams A , Lezana FJ 
Published: December 2009

Griese M, Brasch F, Aldana VR, Cabrera MM, Goelnitz U, Ikonen E, Karam BJ, Liebisch G, Linder MD, Lohse P, Meyer W, Schmitz G, Pamir A, Ripper J, Rolfs A, Schams A, Lezana FJ. Respiratory disease in Niemann‐Pick type C2 is caused by pulmonary alveolar proteinosis.Niemann‐Pick diseases are hereditary neurovisceral lysosomal lipid storage disorders, of which the rare type C2 almost uniformly presents with respiratory distress in early infancy. In the patient presented here, the NPC2 exon 4 frameshift mutation c.408_409delAA caused reduced NPC2 protein levels in serum and lung lavage fluid and the synthesis of an aberrant, larger sized protein of around 28 kDa. Protein expression was strongly reduced also in alveolar macrophages. The infant developed failure to thrive and tachypnea. Lung lavage, computer tomography, and histology showed typical signs of pulmonary alveolar proteinosis with an abnormal intraalveolar accumulation of surfactant as well as macrophages. An NPC2‐hypomorph animal model also showed pulmonary alveolar proteinosis and accumulation of macrophages in the lung, liver, and spleen long before the mice died. Due to the elevation of cholesterol, the surfactant had an abnormal composition and function. Despite the removal of large amounts of surfactant from the lungs by therapeutic lung lavages, this treatment was only temporarily successful and the infant died of respiratory failure. Our data indicate that respiratory distress in NPC2 disease is associated with a loss of normal NPC2 protein expression in alveolar macrophages and the accumulation of functionally inactive surfactant rich in cholesterol.
Adverse effects of trichothiodystrophy DNA repair and transcription gene disorder on human fetal development
Authors: Moslehi R , Signore C , Tamura D , Mills JL , DiGiovanna JJ , Tucker MA , Troendle J , Ueda T , Boyle J , Khan SG , Oh K‐S , Goldstein AM , Kraemer KH 
Published: December 2009

Moslehi R, Signore C, Tamura D, Mills JL, DiGiovanna JJ, Tucker MA, Troendle J, Ueda T, Boyle J, Khan SG, Oh K‐S, Goldstein AM, Kraemer KH. Adverse effects of trichothiodystrophy DNA repair and transcription gene disorder on human fetal development.The effects of DNA repair and transcription gene abnormalities in human pre‐natal life have never been studied. Trichothiodystrophy (TTD) is a rare (affected frequency of 10−6) recessive disorder caused by mutations in genes involved in nucleotide excision repair (NER) pathway and in transcription. Based on our novel clinical observations, we conducted a genetic epidemiologic study to investigate gestational outcomes associated with TTD. We compared pregnancies resulting in TTD‐affected offspring (n = 24) with respect to abnormalities during their antenatal and neonatal periods to pregnancies resulting in their unaffected siblings (n = 18), accounting for correlation, and to population reference values. Significantly higher incidence of several severe gestational complications was noted in TTD‐affected pregnancies. Small for gestational age (SGA) <10th percentile [Relative risk (RR ) = 9.3, 95% CI = 1.4–60.5, p = 0.02], SGA <3rd percentile (RR = 7.2, 95% CI = 1.1–48.1, p = 0.04), and neonatal intensive care unit (NICU) hospitalization (RR = 6.4, 95% CI = 1.4–29.5, p = 0.02) occurred more frequently among TTD‐affected neonates compared with their unaffected siblings. Compared with reference values from general obstetrical population, pregnancies that resulted in TTD‐affected infants were significantly more likely to be complicated by hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome (RR = 35.7, 95% CI = 7.6–92.5, p = 0.0002), elevated mid‐trimester maternal serum human chorionic gonadotropin (hCG) levels (RR = 14.3, 95% CI = 7.0–16.6, p < 0.0001), SGA <3rd percentile (RR = 13.9, 95% CI = 7.4–21.1, p < 0.0001), pre‐term delivery (<32 weeks) (RR = 12.0, 95% CI = 4.9–21.6, p < 0.0001), pre‐eclampsia (RR = 4.0, 95% CI = 1.6–7.4, p = 0.006), and decreased fetal movement (RR = 3.3, 95% CI = 1.6–5.2, p = 0.0018). Abnormal placental development is an underlying mechanism that may explain the constellation of observed complications in our study. Thus, we hypothesize that TTD DNA repair and transcription genes play an important role in normal human placental development.
The impact of sirolimus on hepatocyte proliferation after living donor liver transplantation
Authors: Toso Christian , Patel Seema , Asthana Sonal , Kawahara Toshiyasu , Girgis Safwat , Kneteman Norman N. , Shapiro A.M. James , Bigam David L. 
Published: December 2009

Toso C, Patel S, Asthana S, Kawahara T, Girgis S, Kneteman NN, Shapiro AMJ, Bigam DL. The impact of sirolimus on hepatocyte proliferation after living donor liver transplantation. Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01159.x © 2009 John Wiley & Sons A/S.Abstract: Background:  There is a lack of data on the use of sirolimus after partial liver transplantation, especially regarding its impact on post‐transplant regeneration.Methods:  We reviewed adult living donor transplantations, with de novo sirolimus (n = 7) and without sirolimus (n = 21). Liver biopsies were stained for KI‐67, a proliferation marker. Controls included specimens with normal liver parenchyma (n = 13).Results:  Both groups had similar demographics, graft and patient survival and complication rates. During the first six wk and over the whole first year post‐transplant, the use of sirolimus was associated with lower levels of hepatocyte proliferation compared to sirolimus‐free patients, (overall, 0.3 [0–7.2] vs. 3 [0–49] KI‐67 positive hepatocytes per high power field, p ≤ 0.05). The levels observed in the sirolimus group were similar to those seen in non‐transplanted control patients with normal parenchyma (0.2 [0–1.3], p = NS). Post‐transplant hepatocyte proliferation correlated with the serum levels of sirolimus (p ≤ 0.05), but not with those of tacrolimus or with the dose of mycophenolate mofetil (p = 0.9 and 0.3, respectively).Conclusions:  These data suggest that sirolimus is associated with decreased post‐transplant hepatocyte proliferation. The clinical significance of this observation remains to be fully determined.
Indications for combined liver and kidney transplantation: propositions after a 23‐yr experience
Authors: Ruiz Richard , Jennings Linda W. , Kim Peter , Tomiyama Koji , Chinnakotla Srinath , Fischbach Bernard V. , Goldstein Robert M. , Levy Marlon F. , McKenna Greg J. , Melton Larry B. , Onaca Nicholas , Randall Henry B. , Sanchez Edmund Q. , Susskind Brian M. , Klintmalm Goran B. 
Published: December 2009

Ruiz R, Jennings LW, Kim P, Tomiyama K, Chinnakotla S, Fischbach BV, Goldstein RM, Levy MF, McKenna GJ, Melton LB, Onaca N, Randall HB, Sanchez EQ, Susskind BM, Klintmalm GB. Indications for combined liver and kidney transplantation: propositions after a 23‐yr experience.  Clin Transplant 2010: 24: 807–811. © 2009 John Wiley & Sons A/S.Abstract:  The frequency of combined liver and kidney transplants (CLKT) persists despite the pronounced scarcity of organs. In this review, we sought to ascertain any factors that would reduce the use of these limited commodities. Seventy‐five adult CLKT were performed over a 23‐yr period at our center, 29 (39%) of which occurred during the Model for End‐stage Liver Disease (MELD) era. Overall, patient survival rates were 82%, 73%, and 62% at one, three, and five yr, respectively. There was no difference in patient survival based either on pre‐transplant hemodialysis status or by glomerular filtration rate (GFR) at the time of transplant. Patients undergoing a second CLKT or a liver retransplantation at the time of CLKT had a survival rate of 30% at three months. In the MELD era, patient survival was unchanged (p = NS) despite an older recipient population (p = 0.0029) and a greater number of hepatitis C patients (p = 0.0428). In summary, patients requiring liver retransplantation with concomitant renal failure should be denied CLKT. Renal allografts may also be spared by implementing strict criteria for renal organ allocation (GFR < 30 mL/min at the time of evaluation) and considering the elimination of preemptive kidney transplantation in CLKT.
Effect of Organic Selenium in the Diet on Sperm Quality of Boars
Authors: López A , Rijsselaere T , Van Soom A , Leroy JLMR , De Clercq JBP , Bols PEJ , Maes D 
Published: December 2009

ContentsThe effect of a diet supplemented with organic selenium (Se) on sperm production and quality of boars was investigated. Sixty mature boars from a commercial artificial insemination centre were randomly allocated at Day (D) 0 into Group A and B. Group A received the regular ration supplemented with inorganic Se (0.4 mg/kg feed as Na2SeO3) whereas Group B was switched to the same diet but with organic Se (0.4 mg/kg fed as Se‐yeast). The sperm was investigated during 4 months (D0, D30, D60, D75, D90, D105 and D120). Sperm concentration and motility were objectively measured using a photometer and Computer Assisted Semen Analysis (CASA) respectively. Morphology of the sperm was assessed using eosin–nigrosin staining and the resistance to induction of oxidative stress (production of malonaldehyde, MDA) through thiobarbituric acid reagent species analysis. Additionally, the Se concentration in sperm and blood plasma were measured. Repeated measures analysis of variance (anova) from D60 to 120 (spermatogenesis of approximately 2 months) or anova at D120 (Se concentrations) were used for statistical analysis. The total number of ejaculated sperm was not significantly different between both groups, but boars of Group B had a significantly higher sperm concentration (434.6 vs 514.1 × 106 sperm/ml; p < 0.05). Small differences (p < 0.05) were observed between both groups for some CASA parameters, namely straight line velocity (μm/s) (Group A: 48.3, Group B: 45.1), straightness (%) (Group A: 65.6, Group B: 62.2) and linearity (%) (Group A: 32.2, Group B: 29.3). The sperm of Group B showed more oxidative stress (4.1 vs 4.9 μmol MDA/l; p < 0.05) compared with those of Group A. No significant differences (p > 0.05) were observed for the other parameters. Under the present study conditions, changing from inorganic Se to organic Se in the diet of boars increased sperm concentration but reduced some motility parameters and resistance to oxidative stress.
Genetics of basal cell carcinoma
Authors: De Zwaan Sally E , Haass Nikolas K 
Published: December 2009

ABSTRACTBasal cell carcinoma is the most common human malignancy in populations of European origin, and Australia has the highest incidence of basal cell carcinoma in the world. Great advances in the understanding of the genetics of this cancer have occurred in recent years. Mutations of the patched 1 gene (PTCH1) lead to basal cell carcinoma predisposition in Gorlin syndrome. PTCH1 is part of the hedgehog signalling pathway, and derangements within this pathway are now known to be important in the carcinogenesis of many different cancers including sporadic basal cell carcinoma. The molecular biology of the hedgehog pathway is discussed, and mouse models of basal cell carcinoma based on this pathway are explored. New developments in non‐surgical treatment of basal cell carcinoma are based on this knowledge. Other genes of importance to basal cell carcinoma development include the tumour suppressor gene P53 and the melanocortin‐1 receptor gene. In addition, we discuss molecules of possible importance such as the glutathione‐S‐transferases, DNA repair genes, cyclin‐dependent kinase inhibitor 2A, Brahma and connexins. Evidence of familial aggregation of this cancer is explored and supports the possibility of genetic predisposition to this common malignancy.