bluuebunny/crossref_metadata_2025_split huggingface dataset:
Familial pituitary adenomas
Authors: Tichomirowa M. A. , Daly A. F. , Beckers A. 
Published: April 2009

Abstract.The majority of pituitary adenomas occur sporadically, however, about 5% of all cases occur in a familial setting, of which over half are due to multiple endocrine neoplasia type 1 (MEN‐1) and Carney’s complex (CNC). Since the late 1990s we have described non‐MEN1/CNC familial pituitary tumours that include all tumour phenotypes, a condition named familial isolated pituitary adenomas (FIPA). The clinical characteristics of FIPA vary from those of sporadic pituitary adenomas, as patients with FIPA have a younger age at diagnosis and larger tumours. About 15% of FIPA patients have mutations in the aryl hydrocarbon receptor interacting protein gene (AIP), which indicates that FIPA may have a diverse genetic pathophysiology. This review describes the clinical features of familial pituitary adenomas like MEN1, the MEN 1‐like syndrome MEN‐4, CNC, FIPA, the tumour pathologies found in this setting and the genetic/molecular data that have been recently reported.
The triad of paragangliomas, gastric stromal tumours and pulmonary chondromas (Carney triad), and the dyad of paragangliomas and gastric stromal sarcomas (Carney–Stratakis syndrome): molecular genetics and clinical implications
Authors: Stratakis C. A. , Carney J. A. 
Published: April 2009

Abstract.Carney triad (CT) describes the association of paragangliomas (PGLs) with gastrointestinal stromal tumours (GISTs) and pulmonary chondromas (PCH). A number of other lesions have been described in the condition including pheochromocytomas, oesophageal leiomyomas and adrenocortical adenomas; CT is a novel form of multiple endocrine neoplasia (MEN), a genetic condition with a female predilection. Inactivating mutations of the mitochondrial complex II succinate dehydrogenase (SDH) enzyme subunits SDHB, SDHC and SDHD have been found in familial and sporadic PGLs, and gain‐of‐function mutations of the oncogenes c‐kit (KIT) and platelet‐derived growth factor receptor A (PDGFRA) cause sporadic and familial GISTs. We recently reported an international series of patients with CT, 34 females and three males (median age of presentation 21 years) who did not carry SDHA, SDHB, SDHC, SDHD, KIT or PDGFRA gene mutations. Comparative genomic hybridization revealed a number of DNA copy number changes. The most frequent and greatest contiguous change was a deletion within the 1pcen13‐q21 region, which harbours the SDHC gene. Another frequent change was loss of 1p. Although GISTs showed more frequent losses of 1p than PGLs, the pattern of chromosomal changes was similar in the two tumours despite their different tissue origin and histology; the findings were consistent with a common genetic aetiology of these two tumours in CT. In a separate condition, in which the association (or dyad) of GISTs with PGLs is inherited in an autosomal dominant manner (Carney–Stratakis syndrome, CSS), germline mutations of the SDHB, SDHC and SDHD genes (but not KIT or PDFGRA) were found; GISTs in this condition were caused by SDH deficiency. We conclude that CT is a novel MEN syndrome whose genetic defect remains elusive. CSS is caused by SDH defects, suggesting that sarcomas (GISTs) can be caused by defective mitochondrial oxidation, consistent with recent data implicating this enzyme in a variety of endocrine and other tumours. The above have clinical implications (i) for patients with GISTs that are cKIT‐ and PDGFRA‐mutation negative: these tumours are usually resistant to treatment with currently available tyrosine kinase inhibitors and may be part of a syndrome such as CT or CSS; and (ii) for patients with an inherited PGL syndrome, family history should be explored to identify any other tumours in the family, and in particular other endocrine lesions and GISTs.
Multiple endocrine neoplasia type 1: a chromatin writer’s block
Authors: Dreijerink K. M. A. , Lips C. J. M. , Timmers H. Th. M. 
Published: April 2009

Abstract.Multiple endocrine neoplasia type 1 (MEN1) is caused by inactivating germ line mutations of the MEN1 tumour suppressor gene. The MEN1 gene product, menin, participates in many cellular processes, including regulation of gene transcription. As part of a protein complex that writes a trimethyl mark on lysine 4 of histone H3 (H3K4me3), menin is involved in activating gene transcription. Several functions of the menin histone methyltransferase complex have been discovered through protein interaction studies. Menin can interact with nuclear receptors and regulate transcription of hormone responsive target genes. Menin regulates transcription of cyclin‐dependent kinase inhibitor and Hox genes via the chromatin‐associated factor LEDGF. Aberrant expression of menin target genes in tumours in MEN1 patients suggests that loss of writing of the H3K4me3 mark contributes to MEN1 tumourigenesis. At present, drugs are being developed that target chromatin modifications. The identification of compounds that could restore H3K4me3 on menin target genes would provide new therapeutic strategies for MEN1 patients.
Obesity and trends in cardiovascular risk factors over 40 years in Swedish men aged 50
Authors: Rosengren A. , Eriksson H. , Hansson P. O. , Svärdsudd K. , Wilhelmsen L. , Johansson S. , Welin C. , Welin L. 
Published: April 2009

Abstract.Objective.  To study trends over 40 years in cardiovascular risk factors in normal weight, overweight and obese men, all aged 50 when examined.Design.  Cross‐sectional studies of five successive cohorts of men aged 50.Setting.  City of Göteborg, Sweden.Subjects.  Random population samples of altogether 3251 urban Swedish men born in 1913, 1923, 1933, 1943 and 1953.Main outcome measures.  Anthropometry, cardiovascular risk factors, rates of nonsmoking, normotension and serum cholesterol <5 mmol L−1 over four decades.Results.  Over 40 years, there was a net increase in body mass index (BMI) from 24.8 (SD = 3.2) to 26.4 (3.7) kg m−2 (P < 0.0001), with an increase in the prevalence of obesity (BMI ≥ 30 kg m−2) from 6.0% in 1963 to 13.8% in 2003. Favourable trends with respect to smoking, blood pressure and serum cholesterol were observed similarly amongst normal weight, overweight and obese men. In 1963, 24% of obese men were normotensive compared to 45% in 2003, and 6% had serum cholesterol <5 mmol L−1 compared to 34% in 2003. Compared with obese men in 1963, men who were obese in 2003 had an odds ratio (OR) of 3.39 being a nonsmoker [95% confidence interval (CI): 1.56 to 7.36], 2.67 of being normotensive (1.23 to 5.83) and having serum cholesterol <5 mmol L−1 of 8.30 (2.37 to 29.0). However, optimal risk factor status – no smoking, normotension and total serum cholesterol <5 mmol L−1– was still present in less than one in six men in 2003, similar across BMI categories.Conclusions.  Obese Swedish men who are now in their fifties have much lower levels of other risk factors compared with obese men 40 years ago. This could contribute to explain why coronary heart disease death rates still are falling despite increasing rates of obesity.
Expression of biotransformation genes in woodrat (Neotoma) herbivores on novel and ancestral diets: identification of candidate genes responsible for dietary shifts
Authors: MAGNANOU E. , MALENKE J. R. , DEARING M. D. 
Published: April 2009

AbstractThe ability of herbivores to switch diets is thought to be governed by biotransformation enzymes. To identify potential biotransformation enzymes, we conducted a large‐scale study on the expression of biotransformation enzymes in herbivorous woodrats (Neotoma lepida). We compared gene expression in a woodrat population from the Great Basin that feeds on the ancestral diet of juniper to one from the Mojave Desert that putatively switched from feeding on juniper to feeding on creosote. Juniper and creosote have notable differences in secondary chemistry, and thus, should require different biotransformation enzymes for detoxification. Individuals from each population were fed juniper and creosote diets separately. After the feeding trials, hepatic mRNA was extracted and hybridized to laboratory rat microarrays. Hybridization of woodrat samples to biotransformation probes on the array was 87%, resulting in a total of 224 biotransformation genes that met quality control standards. Overall, we found large differences in expression of biotransformation genes when woodrats were fed juniper vs. creosote. Mojave woodrats had greater expression of 10× as many biotransformation genes as did Great Basin woodrats on a creosote diet. We identified 24 candidate genes that may be critical in the biotransformation of creosote toxins. Superoxide dismutase, a free radical scavenger, was also expressed to a greater extent by the Mojave woodrats and may be important in controlling oxidative damage during biotransformation. The results are consistent with the hypothesis that biotransformation enzymes limit diet switching and that woodrats in the Mojave have evolved a unique strategy for the biotransformation of creosote toxins.
A microarray's view of life in the desert: adding a powerful evolutionary genomics tool to the packrat's midden
Authors: MATOCQ MARJORIE D 
Published: April 2009

Identifying the genetic architecture of adaptive traits is fundamental to understanding how organisms respond to their environment, over both ecological and evolutionary timeframes. Microarray technology that allows us to capture the simultaneous expression of thousands of genes provides unparalleled insight into how organisms cope with their environment at the transcriptional level. Recent studies in Molecular Ecology demonstrate how microarrays can rapidly identify which genes and pathways allow organisms to face some of the most fundamental physiological challenges posed by the environment, including compensation for the hypoxic and thermal stress of high‐altitudes (Cheviron et al. 2008) and, in this issue, the biotransformation of toxic plant secondary compounds by mammals (Magnanou et al. 2009).Microarrays (Ekins et al. 1989; Fodor et al. 1991) are glass slides affixed with hundreds to thousands of oligonucleotide or cDNA sequences (probes). Messenger RNA transcripts (typically reverse transcribed to cDNA) are isolated from a tissue/sample of interest and hybridized to the array. Binding to specific probes indicates that a particular gene was transcriptionally active at or near the time of sampling and thus provides a potentially comprehensive measure of gene expression. Although a tremendously powerful tool, commercially produced oligonucleotide arrays are only available for a handful of model organisms. Nonetheless, evolutionary ecologists have exploited this resource by using a cross‐species hybridization approach (e.g. Saetre et al. 2004), that is, hybridizing a model organism array with a nonmodel sample (Bar‐Or et al. 2007). Magnanou et al. (2009) present a novel example of using a model muroid microarray (Agilent Technologies, Rattus) to study physiological response in a wild, nonmodel muroid, Neotoma.
The innate immunity role of cathepsin‐D is linked to Trp‐491 and Trp‐492 residues of listeriolysin O
Authors: Carrasco‐Marín Eugenio , Madrazo‐Toca Fidel , De Los Toyos Juan R. , Cacho‐Alonso Eva , Tobes Raquel , Pareja Eduardo , Paradela Alberto , Albar Juan Pablo , Chen Wei , Gomez‐Lopez Maria Teresa , Alvarez‐Dominguez Carmen 
Published: April 2009

SummaryListeriolysin O (LLO) is a thiol‐activated cytolysin secreted by Listeria monocytogenes. LLO and phosphatidylinositol phospholipase C are two essential virulence factors, which this bacterium needs to escape from the phagosomal compartment to the cytoplasm. Cathepsin‐D specifically cleaves LLO, between the Trp‐491 (tryptophan amino acid in three letter nomenclature) and Trp‐492 residues of the conserved undecapeptide sequence, ECTGLAWEWWR, in the domain 4 of LLO (D4). Moreover, these residues also correspond to the phagosomal‐binding epitope. Cathepsin‐D had no effect on phosphatidylinositol phospholipase C. We have observed that cathepsin‐D cleaved the related cholesterol‐dependent cytolysin pneumolysin at the same undecapeptide sequence between Trp‐435 and Trp‐436 residues. These studies also revealed an additional cathepsin‐D cleavage site in the pneumolysin D4 domain localized in the 361‐GDLLLD‐366 sequence. These differences might confer a pathogenic advantage to listeriolysin O, increasing its resistance to phagosomal cathepsin‐D action by reducing the number of cleavages sites in the D4 domain. Using ΔLLO/W491A and ΔLLO/W492A bacterial mutants, we reveal that the Trp‐491 residue has an important role linked to cathepsin‐D in Listeria innate immunity.
Structural and kinetic analysis of an MsrA–MsrB fusion protein from Streptococcus pneumoniae
Authors: Kim Young Kwan , Shin Youn Jae , Lee Won‐Ho , Kim Hwa‐Young , Hwang Kwang Yeon 
Published: April 2009

SummaryMethionine sulphoxide reductases (Msr) catalyse the reduction of oxidized methionine to methionine. These enzymes are divided into two classes, MsrA and MsrB, according to substrate specificity. Although most MsrA and MsrB exist as separate enzymes, in some bacteria these two enzymes are fused to form a single polypeptide (MsrAB). Here, we report the first crystal structure of MsrAB from Streptococcus pneumoniae (SpMsrAB) at 2.4 Å resolution. SpMsrAB consists of an N‐terminal MsrA domain, a C‐terminal MsrB domain and a linker. The linker is composed of 13 residues and contains one 310‐helix and several hydrogen bonds interacting with both MsrA and MsrB domains. Interestingly, our structure includes the MsrB domain complexed with an SHMAEI hexa‐peptide that is the N‐terminal region of neighbouring MsrA domain. A kinetic analysis showed that the apparent Km of SpMsrAB for the R‐form‐substrate was 20‐fold lower than that for the S‐form substrate, indicating that the MsrB domain had a much higher affinity for the substrate than the MsrA domain. Our study reveals the first structure of the MsrAB by providing insights into the formation of a disulphide bridge in the MsrB, the structure of the linker region, and the distinct structural nature of active site of each MsrA and MsrB domain.
Combined MRI–PET dissects dynamic changes in plant structures and functions
Authors: Jahnke Siegfried , Menzel Marion I. , Van Dusschoten Dagmar , Roeb Gerhard W. , Bühler Jonas , Minwuyelet Senay , Blümler Peter , Temperton Vicky M. , Hombach Thomas , Streun Matthias , Beer Simone , Khodaverdi Maryam , Ziemons Karl , Coenen Heinz H. , Schurr Ulrich 
Published: April 2009

SummaryUnravelling the factors determining the allocation of carbon to various plant organs is one of the great challenges of modern plant biology. Studying allocation under close to natural conditions requires non‐invasive methods, which are now becoming available for measuring plants on a par with those developed for humans. By combining magnetic resonance imaging (MRI) and positron emission tomography (PET), we investigated three contrasting root/shoot systems growing in sand or soil, with respect to their structures, transport routes and the translocation dynamics of recently fixed photoassimilates labelled with the short‐lived radioactive carbon isotope 11C. Storage organs of sugar beet (Beta vulgaris) and radish plants (Raphanus sativus) were assessed using MRI, providing images of the internal structures of the organs with high spatial resolution, and while species‐specific transport sectoralities, properties of assimilate allocation and unloading characteristics were measured using PET. Growth and carbon allocation within complex root systems were monitored in maize plants (Zea mays), and the results may be used to identify factors affecting root growth in natural substrates or in competition with roots of other plants. MRI–PET co‐registration opens the door for non‐invasive analysis of plant structures and transport processes that may change in response to genomic, developmental or environmental challenges. It is our aim to make the methods applicable for quantitative analyses of plant traits in phenotyping as well as in understanding the dynamics of key processes that are essential to plant performance.
Omega 3 and 6 oils for primary prevention of allergic disease: systematic review and meta‐analysis
Authors: Anandan C. , Nurmatov U. , Sheikh A. 
Published: April 2009

Background:  There is conflicting evidence on the use of omega 3 and omega 6 supplementation for the prevention of allergic diseases. We conducted a systematic review evaluating the effectiveness of omega 3 and 6 oils for the primary prevention of sensitization and development of allergic disorders.Methods:  We searched The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, LILACS, PsycInfo, AMED, ISI Web of Science and Google Scholar for double‐blind randomized controlled trials. Two authors independently assessed articles for inclusion. Meta‐analyses were undertaken using fixed effects modelling, or random effects modelling in the event of detecting significant heterogeneity.Results:  Of the 3129 articles identified, 10 reports (representing six unique studies) satisfied the inclusion criteria. Four studies compared omega 3 supplements with placebo and two studies compared omega 6 supplements with placebo. There was no clear evidence of benefit in relation to reduced risk of allergic sensitization or a favourable immunological profile. Meta‐analyses failed to identify any consistent or clear benefits associated with use of omega 3 [atopic eczema: RR = 1.10 (95% CI 0.78–1.54); asthma: RR = 0.81 (95% CI 0.53–1.25); allergic rhinitis: RR = 0.80 (95% CI 0.34–1.89) or food allergy RR = 0.51 (95% CI 0.10–2.55)] or omega 6 oils [atopic eczema: RR = 0.80 (95% CI 0.56–1.16)] for the prevention of clinical disease.Conclusions:  Contrary to the evidence from basic science and epidemiological studies, our systematic review and meta‐analysis suggests that supplementation with omega 3 and omega 6 oils is probably unlikely to play an important role as a strategy for the primary prevention of sensitization or allergic disease.
Evaluating the potential impact of mismatches outside the antigen recognition site in unrelated hematopoietic stem cell transplantation: HLA‐DRB1*1454 and DRB1*140101
Authors: Xiao Y. , Lazaro A. M. , Masaberg C. , Haagenson M. , Vierra‐Green C. , Spellman S. , Dakshanamurthy S. , Ng J. , Hurley C. K. 
Published: April 2009

AbstractDNA sequencing of 268 individuals drawn from four US populations carrying two unresolved DRB1*14 alleles differing only outside the antigen recognition site identified DRB1*1454 in the majority. A database of 4222 human leukocyte antigen (HLA)‐matched hematopoietic stem cell transplantation donor–recipient pairs was queried to determine the number likely mismatched for DRB1*140101/DRB1*1454 but matched for class I loci. A power calculation suggests that more than 88,000 transplants among European Americans will be needed to identify sufficient 7/8 allele‐matched pairs to evaluate the impact of the DRB1*140101/DRB1*1454 mismatch on transplant outcome. Molecular modeling of the HLA‐DR interaction with the T‐cell receptor and with CD4 suggests that the amino acid substitution distinguishing the two alleles will have minimal impact on allorecognition.
Effects of individual and population parameters on reproductive success in three sexually deceptive orchid species
Authors: Vandewoestijne S. , Róis A. S. , Caperta A. , Baguette M. , Tyteca D. 
Published: April 2009

AbstractReproductive success (RS) in orchids in general, and in non‐rewarding species specifically, is extremely low. RS is pollinator and pollination limited in food deceptive orchids, but this has rarely been studied in sexually deceptive orchid species. Here, we tested the effects of several individual (plant height, inflorescence size, nearest neighbour distance and flower position) and population (patch geometry, population density and size) parameters on RS in three sexually deceptive Ophrys (Orchidaceae) species. Inter‐specific differences were observed in RS of flowers situated in the upper versus the lower part of the inflorescence, likely due to species‐specific pollinator behaviour. For all three species examined, RS increased with increasing plant height, inflorescence size and nearest neighbour distance. RS generally increased with decreasing population density and increasing patch elongation. Given these results, we postulate that pollinator availability, rather than pollinator learning, is the most limiting factor in successful reproduction for sexually deceptive orchids. Our results also suggest that olfactory ‘display’ (i.e. versus optical display), in terms of inflorescence size (and co‐varying plant height), plays a key role in individual RS of sexually deceptive orchids. In this regard, several hypotheses are suggested and discussed.
Variation in sclerophylly among Iberian populations of Quercus coccifera L. is associated with genetic differentiation across contrasting environments
Authors: Rubio de Casas R. , Vargas P. , Pérez‐Corona E. , Cano E. , Manrique E. , García‐Verdugo C. , Balaguer L. 
Published: April 2009

AbstractEvergreen oaks are an emblematic element of the Mediterranean vegetation and have a leaf phenotype that seems to have remained unchanged since the Miocene. We hypothesise that variation of the sclerophyll phenotype among Iberian populations of Quercus coccifera is partly due to an ulterior process of ecotypic differentiation. We analysed the genetic structure of nine Iberian populations using ISSR fingerprints, and their leaf phenotypes using mean and intracanopy plasticity values of eight morphological (leaf angle, area, spinescence, lobation and specific area) and biochemical traits (VAZ pool, chlorophyll and β‐carotene content). Climate and soil were also characterised at the population sites. Significant genetic and phenotypic differences were found among populations and between NE Iberia and the rest of the populations of the peninsula. Mean phenotypes showed a strong and independent correlation with both genetic and geographic distances. Northeastern plants were smaller, less plastic, with smaller, spinier and thicker leaves, a phenotype consistent with the stressful conditions that prevailed in the steppe environments of the refugia within this geographic area during glaciations. These genetic, phenotypic, geographic and environmental patterns are consistent with previously reported palaeoecological and common evidence. Such consistency leads us to conclude that there has been a Quaternary divergence within the sclerophyllous syndrome that was at least partially driven by ecological factors.