bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constitutive RET tyrosine kinase activation in hereditary medullary thyroid cancer: clinical opportunities
Authors: Machens A. , Lorenz K. , Dralle H. 
Published: April 2009

Abstract.The ground‐breaking discovery of genotype–phenotype relationships in hereditary medullary thyroid cancer has greatly facilitated early prophylactic thyroidectomy. Its timing depends not solely on a positive gene test but, more importantly, on the type of the REarranged during Transfection (RET) mutation and its underlying mode of RET receptor tyrosine kinase activation. In the past decade, the therapeutic corridor opened by molecular information has been defined down to a remarkable level of detail. Based on mutational risk profiles, preemptive thyroidectomy is recommended at 6 months of age for carriers of highest‐risk mutations, before the age of 5 years for carriers of high‐risk mutations, and before the age of 5 or 10 years for carriers of least‐high‐risk mutations. Additional lymph node dissection may not be needed in the absence of increased preoperative basal calcitonin levels. Better comprehension of RET function should enable the design of targeted therapies for RET carriers beyond surgical cure in whom the DNA‐based ‘window of opportunity’ has been missed.
Use of mouse models to understand the molecular basis of tissue‐specific tumorigenesis in the Carney complex
Authors: Kirschner L. S. 
Published: April 2009

Abstract.Carney complex (CNC) is an autosomal dominant, multiple endocrine neoplasia syndrome comprised of spotty skin pigmentation, myxomatosis, endocrine tumours and schwannomas. The majority of cases are due to inactivating mutations in PRKAR1A, the gene encoding the type 1A regulatory subunit of the 3′,5′‐cyclic adenosine monophosphate (cAMP)‐dependent protein kinase, PKA (protein kinase A). In order to understand the molecular basis for tumorigenesis associated with PRKAR1A mutations, we have developed conventional and conditional Prkar1a knockout (KO) mice as well as primary cell culture models corresponding to these genetic manipulations. At the biochemical level, removal of Prkar1a from cells causes enhanced PKA activity, the same effect which has been observed in tumours isolated from CNC patients. Mice heterozygous for Prkar1a mutations (the exact genetic model for CNC patients) are born at expected frequencies and are tumour prone, developing neoplasms in cAMP‐responsive cell types such as Schwann cells, osteoblasts and thyrocytes. In order to understand the basis of tissue‐specific tumour formation, we have created tissue‐specific KOs of the gene from three different tissues: the neural crest (Schwann cells), the pituitary gland and the heart. In the neural crest and the pituitary, ablation of Prkar1a leads to excess proliferation and tumorigenesis, whereas the same manipulation in developing cardiomyocytes leads to reduced proliferation and embryonic demise. The KO hearts also exhibit myxomatous changes suggesting a connection between PKA activation and myxomagenesis, although the nature of this relationship has not yet been determined. This work confirms the role of Prkar1a as a tissue‐specific tumour suppressor, and ongoing work is focused on identifying the key downstream signalling targets affected by dysregulation of PKA.
Coordination of cell proliferation and cell expansion mediated by ribosome‐related processes in the leaves of Arabidopsis thaliana
Authors: Fujikura Ushio , Horiguchi Gorou , Ponce María Rosa , Micol José Luis , Tsukaya Hirokazu 
Published: April 2009

SummaryCo‐ordination of cell proliferation and cell expansion is a key regulatory process in leaf‐size determination, but its molecular details are unknown. In Arabidopsis thaliana, mutations in a positive regulator of cell proliferation often trigger excessive cell enlargement post‐mitotically in leaves. This phenomenon, called compensation syndrome, is seen in the mutant angustifolia3 (an3), which is defective in a transcription co‐activator. Such compensation, however, does not occur in response to a decrease in cell number in oligocellula (oli). oli2, oli5 and oli7 did not exhibit compensation and the reduction in cell number in these mutants was moderate. However, when an oli mutation was combined with a different oli mutation to create a double mutant, cell number was further reduced and compensation was induced. Similarly, weak suppression of AN3 expression reduced cell number moderately but did not induce compensation compared with an an3 null mutant. Furthermore, double mutants of either oli2, oli5 or oli7 and an3 showed markedly enhanced compensation. These results suggest that compensation is triggered when cell proliferation regulated by OLI2/OLI5/OLI7 and AN3 is compromised in a threshold‐dependent manner. OLI2 encodes a Nop2 homolog in Saccharomyces cerevisiae that is involved in ribosome biogenesis, whereas OLI5 and OLI7 encode ribosome proteins RPL5A and RPL5B, respectively. This suggests that a factor involved in the induction of compensation may be under the dual control of AN3 and a ribosome‐related process.
High frequency of single‐copy T‐DNA transformants produced by floral dip in CRE‐expressing Arabidopsis plants
Authors: De Paepe Annelies , De Buck Sylvie , Hoorelbeke Katleen , Nolf Jonah , Peck Ingrid , Depicker Anna 
Published: April 2009

SummaryFor genetic transformation of plants, floral dip with Agrobacterium often results in integration of multiple T‐DNA copies at a single locus and frequently in low and unstable transgene expression. To obtain efficient single‐copy T‐DNA transformants, two CRE/loxP recombinase‐based simplifying strategies for complex T‐DNA loci were compared. A T‐DNA vector with oppositely oriented loxP sites was transformed into CRE‐expressing and wild‐type control Arabidopsis thaliana plants. Of the primary CRE‐expressing transformants, 55% harboured a single copy of the introduced T‐DNA, but only 15% in the wild‐type plants. However, 73% of the single‐copy transformants in the CRE background showed continuous somatic inversion of the DNA segment between the two loxP sites. To avoid inversion of the loxP‐flanked T‐DNA segment, two T‐DNA vectors harbouring only one loxP site were investigated for their suitability for CRE/loxP recombinase‐mediated resolution upon floral‐dip transformation into CRE‐expressing plants. On average, 70% of the transformants in the CRE background were single‐copy transformants, whereas the single‐copy T‐DNA frequency was only 11% for both vectors in the wild‐type background. Both resolution strategies yielded mostly Cre transformants in which the 35S‐driven transgene expression was stable and uniform in the progeny and remarkably, also in Cre transformants with multiple T‐DNA copies. Therefore, a role is proposed for the CRE recombinase in preventing inverted T‐DNA repeat formation or modifying the locus chromatin structure, resulting in a reduced sensitivity for silencing.
AAP1 regulates import of amino acids into developing Arabidopsis embryos
Authors: Sanders Ann , Collier Ray , Trethewy Alexander , Gould Grant , Sieker Renate , Tegeder Mechthild 
Published: April 2009

SummaryThe embryo of Arabidopsis seeds is symplasmically isolated from the surrounding seed coat and endosperm, and uptake of nutrients from the seed apoplast is required for embryo growth and storage reserve accumulation. With the aim of understanding the importance of nitrogen (N) uptake into developing embryos, we analysed two mutants of AAP1 (At1g58360), an amino acid transporter that was localized to Arabidopsis embryos. In mature and desiccated aap1 seeds the total N and carbon content was reduced while the total free amino acid levels were strongly increased. Separately analysed embryos and seed coats/endosperm of mature seeds showed that the elevated amounts in amino acids were caused by an accumulation in the seed coat/endosperm, demonstrating that a decrease in uptake of amino acids by the aap1 embryo affects the N pool in the seed coat/endosperm. Also, the number of protein bodies was increased in the aap1 endosperm, suggesting that the accumulation of free amino acids triggered protein synthesis. Analysis of seed storage compounds revealed that the total fatty acid content was unchanged in aap1 seeds, but storage protein levels were decreased. Expression analysis of genes of seed N transport, metabolism and storage was in agreement with the biochemical data. In addition, seed weight, as well as total silique and seed number, was reduced in the mutants. Together, these results demonstrate that seed protein synthesis and seed weight is dependent on N availability and that AAP1‐mediated uptake of amino acids by the embryo is important for storage protein synthesis and seed yield.
VERNALIZATION INSENSITIVE 3 (VIN3) is required for the response of Arabidopsis thaliana seedlings exposed to low oxygen conditions
Authors: Bond Donna M. , Wilson Iain W. , Dennis Elizabeth S. , Pogson Barry J. , Jean Finnegan E. 
Published: April 2009

Summary VERNALIZATION INSENSITIVE 3 (VIN3), which is required for the vernalization‐mediated epigenetic repression of FLOWERING LOCUS C (FLC) in Arabidopsis thaliana, is quantitatively induced in response to low temperatures. We found that hypoxic conditions also induce VIN3 in a quantitative manner but high salt, high temperatures and osmotic stress do not. Inhibition of mitochondrial respiration did not induce VIN3 expression, consistent with the lack of VIN3 induction in response to other stresses that affect the rate of mitochondrial respiration. De novo protein synthesis is required for VIN3 induction during hypoxic conditions; this situation is not the case for VIN3 induction by low temperatures, indicating that different mechanisms act to induce VIN3 expression in response to cold and hypoxic conditions. Without VIN3 activity, fewer seedlings survived following a 72‐h period of hypoxic treatment, indicating that VIN3 is required for the survival of Arabidopsis thaliana in response to hypoxic stress. Complementation of the vin3 mutant with a VIN3 transgene restored the wild‐type response to low oxygen and confirmed the role of VIN3 in protecting both shoots and roots during low oxygen conditions. Loss of VIN3 protein did not affect the transcriptional regulation of genes known to be important in the response to low oxygen stress, which suggests that there is a novel mechanism to combat hypoxia that involves VIN3. This mechanism is likely to involve chromatin remodelling and may be similar to the role of VIN3 in the epigenetic repression of FLC during the vernalization response.
Predicting weed emergence in maize crops under two contrasting climatic conditions
Authors: DORADO J , SOUSA E , CALHA I M , GONZÁLEZ‐ANDÚJAR J L , FERNÁNDEZ‐QUINTANILLA C 
Published: April 2009

SummaryPredictive empirical models of the timing of emergence were developed for ten major weed species in maize crops. Monitoring of seedling emergence was performed over two years in two maize fields located in Central Spain and Tagus Valley in Portugal. Thermal time was used as the independent variable for predicting cumulative emergence. Different non‐linear growth curves were fitted to the data sets of cumulative percent emergence for the different species, sites and years using genetic algorithms. Based on their emergence patterns, weed species were arranged into three groups. Species with early‐season emergence (Abutilon theophrasti, Xanthium strumarium, Datura stramonium, Datura ferox, Sorghum halepense, Digitaria sanguinalis and Echinochloa crus‐galli) reached 70% emergence with less than 700 growing day degrees (GDD). Species with whole‐season emergence (Cyperus rotundus and Solanum nigrum) started early their emergence processes but the emergence continued throughout the maize life‐cycle; they required up to 1300 GDD to reach 70% emergence. The only species with late‐season emergence was Sonchus oleraceus; it required more than 1300 GDD to reach 70% emergence. The results obtained in our experiments have shown a good synchrony between the predictions obtained in different years in the same site. However, no single model was able to predict the timing of emergence in two sites with different environmental conditions, challenging the hypothesis that a single general model, based on temperature only, can be used to predict weed emergence in different geographical locations.
The association between HLA‐A, ‐B alleles and major histocompatibility complex class I polymorphic Alu insertions in four populations in China
Authors: Yao Y. , Shi L. , Shi L. , Lin K. , Yu L. , Sun H. , Huang X. , Tao Y. , Yi W. , Liu S. , Chu J. 
Published: April 2009

AbstractThe study of the association between polymorphic Alu insertions [human leukocyte antigen (HLA)‐Alu] at five loci and HLA class I alleles at two loci allows for better identification of the origins and evolution of HLA class I region haplotypes in different populations. In the present study, we determined the frequencies of five HLA‐Alus and their associations with HLA‐A and ‐B alleles in Han, Wa, Maonan, and Jinuo populations. Our results showed a strong association between AluHG insertion and HLA‐A*02 in all populations studied; however, the associations between AluHJ insertion and HLA‐A*1101 and HLA‐A*2402 and AluHF insertion and HLA‐A*2601 were only observed in Han. The AluMICB insertion showed a strong association with HLA‐B*5502 in Han, Maonan, and Jinuo. HLA‐A*0101, HLA‐A*0201, HLA‐A*0203, HLA‐A*1101, HLA‐A*2402, HLA‐A*2601, and HLA‐A*3101 alleles were associated with one or more of the three different Alu elements within the alpha block as independent haplotypes, and HLA‐A*0101, HLA‐A*0201, HLA‐A*0203, HLA‐A*1101, and HLA‐A*2402 alleles were associated with at least two different Alu insertions as a haplotype within the alpha block. We conclude that the HLA class I region haplotypes of the four populations were derived from different progenitor haplotypes, and relatively high rates of recombination between individuals with HLA‐A alleles and different HLA‐Alus occurred in this region.
Role of polymorphisms in the TNFRSF13B (TACI) gene in Spanish patients with immunoglobulin A deficiency
Authors: López‐Mejías R. , Del Pozo N. , Fernández‐Arquero M. , Ferreira A. , García‐Rodríguez M. C. , De La Concha E. G. , Fontán G. , Urcelay E. , Martínez A. , Núñez C. 
Published: April 2009

AbstractMutations in the TNFRSF13B (TACI) gene have been associated with common variable immunodeficiency, and a role in immunoglobulin A deficiency (IgAD) has also been suggested. We aimed at studying the role of several polymorphisms along this gene in IgAD susceptibility. Three TNFRSF13B mutations (C104R, A181E and R202H) and eight additional single nucleotide polymorphisms in the gene were genotyped in 338 Spanish IgAD patients and 553 ethnically matched healthy controls and tested for association. Data from parents of 114 IgAD patients were also collected and used for additional analysis. No statistically significant differences were observed after comparing patients and controls for any single nucleotide polymorphism analysed. Therefore, our work seems to discard a role of TNFRSF13B mutations in IgAD, concordantly with the most recent published studies.
Liver transplantation for an infant with neonatal intrahepatic cholestasis caused by citrin deficiency using heterozygote living donor
Authors: Shigeta Takanobu , Kasahara Mureo , Kimura Takuya , Fukuda Akinari , Sasaki Kazunari , Arai Katsuhiro , Nakagawa Atsuko , Nakagawa Satoshi , Kobayashi Keiko , Soneda Shun , Kitagawa Hiroaki 
Published: April 2009

Shigeta T, Kasahara M, Kimura T, Fukuda A, Sasaki K, Arai K, Nakagawa A, Nakagawa S, Kobayashi K, Soneda S, Kitagawa H. Liver transplantation for an infant with neonatal intrahepatic cholestasis caused by citrin deficiency using heterozygote living donor. Pediatr Transplantation 2010: 14:E86–E88. © 2009 John Wiley Sons & A/S.Abstract:  NICCD is an autosomal recessive genetic disorder, characterized by cholestasis, coagulopathy, hypoglycemia, fatty liver and multiple amino acidemia. NICCD develops in the neonatal/infantile period and has been reported as a “naturally curable” disease within one yr of life. Recently, we experienced an infantile NICCD who developed progressive liver failure, and required subsequent LT using a heterozygote living donor at eight months of age. Diagnosis of NICCD was established before transplantation, and donor evaluation included mutation in the SLC25A13 gene for exclusion of individuals with citrin deficiency citrullinemia. LDLT, from blood type identical mother using a left lateral segment graft, was performed without serious complication. Plasma amino acid concentration was normalized rapidly, and the patient was discharged 30 days after transplant. During one yr follow up, the recipient has been doing well without additional medication for NICCD. NICCD should be considered in the differential diagnosis as a cause of neonatal/infantile cholestatic disease. LT using a heterozygote living donor is an effective alternative in countries where a deceased donor is not available.
Clinical manifestations and survival of hepatocellular carcinoma patients with peritoneal metastasis
Authors: Lin Chien‐Chu , Liang Hsiao‐Ping , Lee Hsuan‐Shu , Huang Guan‐Tarn , Yang Pei‐Ming , Ho Ming‐Chih , Lee Po‐Huang , Tsang Yuk‐Ming , Chen Ding‐Shinn , Sheu Jin‐Chuan , Chen Chien‐Hung 
Published: April 2009

AbstractBackground and Aim:  Peritoneal metastasis is an uncommon manifestation of hepatocellular carcinoma (HCC). The aim of the present paper was to investigate the characteristics and survival of HCC patients with peritoneal metastases.Methods:  From January 1985 to December 2004, we retrospectively reviewed the records of 53 Taiwanese HCC patients with peritoneal metastases.Results:  Peritoneal metastases were detected at the time of HCC diagnosis (synchronously) in 10 patients and after the initial therapy for the primary tumors (metachronously) in 43 patients. The mean time for development of the metachronous peritoneal metastases was similar whether the primary cancer was treated with surgery (24 months) or transarterial chemoembolization (22.2 months). The single patient whose primary cancer was treated with supportive care alone developed peritoneal metastasis only 7.5 months after detection of the primary cancer. Surgical resection of the peritoneal metastases was possible in two‐thirds of the 43 metachronous patients. The median survival for those who received surgery for these metastases was 12.5 months vs. 2.1 months for those without surgery (P = 0.0013). However, there was no difference in survival if patients were stratified to Child‐Pugh grade.Conclusions:  Peritoneal metastases of HCC are rare and can occur synchronously or metachronously. Though increased long‐term survival was found in patients who had surgical removal of peritoneal metastases, the main determinant of better survival is Child‐Pugh grade.
Vertebrate range sizes indicate that mountains may be ‘higher’ in the tropics
Authors: McCain Christy M. 
Published: April 2009

AbstractIn 1967, Daniel Janzen proposed the influential, but largely untested hypothesis, that tropical mountain passes are physiologically higher than temperate mountains. I test his key prediction, the one upon which all the others rely: namely, that elevational range sizes of organisms get larger on mountains at increasing latitudes. My analyses use 170 montane gradients spanning 36.5° S to 48.2° N latitude compiled from over 80 years of research and 16 500 species of rodents, bats, birds, lizards, snakes, salamanders, and frogs. In support of Janzen’s prediction, I find that elevational range size increases with increasing latitude for all vertebrate groups except rodents. I document additional lines of evidence for temperature variability as a plausible mechanism for trends in vertebrate range size, including strong effects of thermoregulation and daily temperature variability, and a weak effect of precipitation.
Socioeconomic factors related to attendance at a Type 2 diabetes screening programme
Authors: Dalsgaard E‐M. , Lauritzen T. , Christiansen T. , Mai K. S. , Borch‐Johnsen K. , Sandbæk A. 
Published: April 2009

AbstractAims  The prevalence of diabetes is increasing, and screening of high‐risk populations is recommended. A low attendance rate has been observed in many Type 2 diabetes screening programmes, so that an analysis of factors related to attendance is therefore relevant. This paper analyses the association between socioeconomic factors and attendance for Type 2 diabetes screening.Methods  Persons aged 40–69 years (n = 4603) were invited to participate in a stepwise diabetes screening programme performed in general practitioners’ offices in the county of Aarhus, Denmark in 2001. The study was population‐based and cross‐sectional with follow‐up. The association between screening attendance in the high‐risk population and socioeconomic factors was analysed by odds ratio.Results  Forty‐four percent of the estimated high‐risk population attended the screening programme. In those with known risk for Type 2 diabetes, attenders were more likely to be older, to be unemployed and to live in the countryside than non‐attenders. The risk for Type 2 diabetes was unknown for 21% of the study population; this group was younger and less likely to be cohabitant, skilled, or employed and to have middle or high income than the study population with known risk score for diabetes.Conclusions  A low attendance rate was found in this screening programme for Type 2 diabetes. No substantial socioeconomic difference was found between attenders and non‐attenders in the high‐risk population. Further research is needed to uncover barriers to screening of Type 2 diabetes in socioeconomically deprived persons.
Alkalinization of urine samples preserves albumin concentrations during prolonged frozen storage in patients with diabetes mellitus
Authors: Lambers Heerspink H. J. , Nauta F. L. , Van Der Zee C. P. , Brinkman J. W. , Gansevoort R. T. , De Zeeuw D. , Bakker S. J. L. 
Published: April 2009

AbstractBackground  In epidemiological studies in patients with diabetes, urine samples are often stored frozen prior to assessment of urinary albumin concentration (UAC). However, prolonged frozen storage may result in a falsely low UAC. In the current study, we investigated whether adjustment of urinary pH to alkaline values prior to frozen storage can prevent this problem.Methods  Urine samples were collected in 90 patients from our diabetes outpatient clinic and divided into two portions. One portion was first adjusted to pH > 8.0 with 0.1 m sodium hydroxide, the other was left unprocessed. Both portions were divided into aliquots. UAC was assessed in fresh samples and after 7 days, 1, 6 and 12 months of storage at −20 and −80°C.Results  Until 1 month of storage there were no significant changes in UAC. After longer storage, UAC fell significantly in pH unadjusted samples stored at −20°C, with a −7.6% (27.8) and −13.6% (31.7) change after 6 and 12 months storage, respectively. No significant change in UAC occurred in pH adjusted samples stored at −20°C or when samples were stored at −80°C, both with and without pH adjustment. Variation in UAC assessed after 12 months of storage was larger for samples stored at −20°C without adjustment of pH than for the samples stored with pH adjustment or stored at −80°C.Conclusions  Urine alkalinization to pH > 8.0 prevents the decline in UAC associated with 12 months of frozen storage at −20°C and results in lower variation between samples after storage.