bluuebunny/crossref_metadata_2025_split huggingface dataset:
RAS Mutations Are the Predominant Molecular Alteration in Poorly Differentiated Thyroid Carcinomas and Bear Prognostic Impact
Authors: Volante Marco , Rapa Ida , Gandhi Manoj , Bussolati Gianni , Giachino Daniela , Papotti Mauro , Nikiforov Yuri E. 
Published: January 2014

ABSTRACT

Context
Poorly differentiated carcinomas represent an aggressive group of thyroid tumors with controversial classification placement and poorly understood pathogenesis. Molecular data in this group of tumors are extremely heterogeneous, possibly reflecting different inclusion criteria. Recently homogeneous diagnostic criteria have been proposed by our group (Turin proposal) that need to be complemented by detailed molecular characterization.

Objective
The objective of the study was to define a comprehensive molecular typing of poorly differentiated thyroid carcinomas classified following homogeneous diagnostic criteria.

Design
Sixty-five cases of poorly differentiated carcinoma selected following the Turin proposal have been screened for N-, K-, H-RAS, BRAF, RET/PTC1 and 3, and PAX8/PPARγ mutations-rearrangements using alternative techniques and in two different laboratories. Molecular data were compared with clinical pathological parameters and survival by univariate and multivariate analysis.

Results
RAS mutations in codon 61 were by far the most common genetic alteration in poorly differentiated carcinomas (23% of cases), with all mutation in NRAS except one in the HRAS gene. A single BRAF mutation was found in a poorly differentiated carcinoma with a residual component of a tall cell variant of papillary carcinoma. No KRAS, RET/PTC, or PAX8/PPARγ genetic alteration was detected. In this series, the presence of RAS mutations was a unique negative prognostic parameter at multivariate analysis.

Conclusions
The present study demonstrates that strictly classified poorly differentiated carcinomas are genetically homogeneous, RAS mutations being the almost exclusive genetic event. Moreover, the detection of RAS mutations might be clinically relevant for the prognostic stratification of these tumors.
Abrogation of TLR4 and CD14 Expression and Signaling in Human Adrenocortical Tumors
Authors: Kanczkowski Waldemar , Tymoszuk Piotr , Ehrhart-Bornstein Monika , Wirth Manfred P. , Zacharowski Kai , Bornstein Stefan R. 
Published: January 2014

Abstract
Context: Adrenocortical carcinoma (ACC) is a rare tumor with poor prognosis. The expression of innate immunity receptor Toll-like receptor (TLR)-4 was recently reported in various human tumors, and TLR4 was shown to regulate tumor immune escape processes, proliferation, and resistance to chemotherapeutical agents.
Objective: The aim of this study was to investigate TLR4 expression, signaling, and function in the process of tumorigenesis in the human adrenal cortex.
Measurements and Main Results: Real-time PCR analysis of human ACC (n = 8), adenoma (n = 8), and ACC cell lines (SW13, NCI-H295R, and HAC15) revealed a significant down-regulation of TLR4, MD2, and CD14 mRNA compared with normal human adrenal cortex and adrenocortical cells in primary culture. Furthermore, immunohistochemistry revealed an abrogation of TLR4 and CD14 expression in ACC but not adenoma tissues. Western blot analysis of MAPK, AKT, activator protein-1, and nuclear factor-κB signaling revealed that the ACC cell lines are unresponsive to lipopolysaccharide action. Restoration of TLR4 signaling by stable transfection of TLR4-CD14 plasmid into NCI-H295R cells sensitized them to lipopolysaccharide incubation as shown by nuclear factor-κB activation and decreased cell viability and induced apoptosis in these cells.
Conclusion: Our results demonstrate a significant reduction in the expression of TLR4 and CD14 and an inactivation of TLR4 signaling in ACCs. Furthermore, our data show that reintroduction of TLR4 expression in ACCs may provide a novel therapeutic strategy for adrenal cancer.
Wnt/β-Catenin Pathway Activation in Adrenocortical Adenomas Is Frequently due to Somatic CTNNB1-Activating Mutations, Which Are Associated with Larger and Nonsecreting Tumors: A Study in Cortisol-Secreting and -Nonsecreting Tumors
Authors: Bonnet Stéphane , Gaujoux Sébastien , Launay Pierre , Baudry Camille , Chokri Ilham , Ragazzon Bruno , Libé Rossella , René-Corail Fernande , Audebourg Anne , Vacher-Lavenu Marie-Cécile , Groussin Lionel , Bertagna Xavier , Dousset Bertrand , Bertherat Jérôme , Tissier Frédérique 
Published: January 2014

Abstract
Background: Abnormal β-catenin immunohistochemistry and mutations of the β-catenin gene (CTNNB1) have been reported in adrenocortical adenomas (ACAs), but the frequencies of these defects and the phenotype of such tumors have not been clearly determined.
Objective: The objective of the study was to describe the Wnt/β-catenin pathway alterations in 100 ACAs and their association with clinicopathological characteristics.
Patients and methods: One hundred consecutive ACAs (excluding Conn’s adenomas) were studied clinically by β-catenin immunohistochemistry and direct sequencing of CTNNB1.
Results: Thirty-five ACAs were nonsecreting adenomas (NSAs), 19 were subclinical cortisol secreting adenomas (SCSAs), and 46 were cortisol secreting adenomas (CSAs). Fifty-one tumors had abnormal cytoplasmic and/or nuclear β-catenin immunohistochemical staining, indicating Wnt/β-catenin pathway alteration. Thirty-six tumors showed CTNNB1 mutations, which all showed abnormal immunohistochemical β-catenin accumulation. Among the 64 nonmutated tumors, only 15 (23%) showed cytoplasmic and/or nuclear β-catenin staining (P &lt; 0.0001). Tumors with CTNNB1 mutations were predominantly nonsecreting (61% NSAs, 22% SCSAs, 16% CSAs) whereas nonmutated tumors were predominantly secreting (20% NSAs, 17% SCSAs, 62% CSAs) (P &lt; 0.0001). Mean tumor size and weight were, respectively, 4.2 cm (±1.2) and 28.4 g (±21.1) for tumors with CTNNB1 mutations vs. 3.4 cm (±0.9) and 18.2 g (±8.1) for nonmutated tumors (P &lt; 0.01).
Conclusions: Abnormal cytoplasmic and/or nuclear β-catenin immunohistochemical staining occurs in about half of ACAs. This suggests the activation of the Wnt/β-catenin pathway, which could be explained by activating mutations of CTNNB1 in 70% of the cases. CTNNB1 mutations are mainly observed in larger and nonsecreting ACAs, suggesting that the Wnt/β-catenin pathway activation is associated with the development of less differentiated ACAs.
Effect of Glucagon-Like Peptide-1 on α- and β-Cell Function in C-Peptide-Negative Type 1 Diabetic Patients
Authors: Kielgast Urd , Asmar Meena , Madsbad Sten , Holst Jens J. 
Published: January 2014

Abstract
Context: The mechanism by which glucagon-like peptide-1 (GLP-1) suppresses glucagon secretion is uncertain, and it is not determined whether endogenous insulin is a necessary factor for this effect.
Objective: Our objective was to characterize the α- and β-cell responses to GLP-1 in type 1 diabetic patients without residual β-cell function.
Methods: Nine type 1 diabetic patients, classified as C-peptide negative by a glucagon test, were clamped at plasma glucose of 20 mmol/liter for 90 min with arginine infusion at time 45 min and concomitant infusion of GLP-1 (1.2 pmol/kg · min) or saline.
Results: Infusion with GLP-1 increased C-peptide concentration just above the detection limit of 33 pmol/liter in one patient, but C-peptide remained immeasurable in all other patients. In the eight remaining patients, total area under the curve of glucagon was significantly decreased with GLP-1 compared with saline: 485 ± 72 vs. 760 ± 97 pmol/liter · min (P &lt; 0.001). In addition, GLP-1 decreased the arginine-stimulated glucagon release (incremental AUC of 103 ± 21 and 137 ± 16 pmol/liter · min, with GLP-1 and saline, respectively, P &lt; 0.05).
Conclusions: In type 1 diabetic patients without endogenous insulin secretion, GLP-1 decreases the glucagon secretion as well as the arginine-induced glucagon response during hyperglycemia. GLP-1 induced endogenous insulin secretion in one of nine type 1 diabetic patients previously classified as being without endogenous insulin secretion.
Sterol O-Acyltransferase 1 (SOAT1, ACAT) Is a Novel Target of Steroidogenic Factor-1 (SF-1, NR5A1, Ad4BP) in the Human Adrenal
Authors: Ferraz-de-Souza Bruno , Hudson-Davies Rebecca E. , Lin Lin , Parnaik Rahul , Hubank Mike , Dattani Mehul T. , Achermann John C. 
Published: January 2014

Abstract

Context:
Steroidogenic factor-1 (SF-1, NR5A1, Ad4BP) is a master regulator of adrenal development and steroidogenesis. Defects in several known targets of SF-1 can cause adrenal disorders in humans.

Objective:
We aimed to identify novel targets of SF-1 in the human adrenal. These factors could be important regulators of adrenal development and steroidogenesis and potential candidates for adrenal dysfunction.

Design:
A gene discovery strategy was developed based on bidirectional manipulation of SF-1. Overexpression or knockdown of SF-1 in NCI-H295R human adrenocortical cells was used to identify a subset of positively-regulated SF-1 targets.

Results:
This approach identified well-established SF-1 target genes (STAR, CYP11A) and several novel genes (VSNL1, ZIM2, PEG3, SOAT1, and MTSS1). Given its role in cholesterol metabolism, sterol O-acyltransferase 1 (SOAT1, previously referred to as acyl-Coenzyme A:cholesterol acyltransferase 1, ACAT) was studied further and found to be expressed in the developing human fetal adrenal cortex. We hypothesized that impaired SOAT1 activity could result in adrenal insufficiency through reduced cholesteryl ester reserves or through toxic destruction of the adrenal cells during development. Therefore, mutational analysis of SOAT1 in a cohort of 43 patients with unexplained adrenal insufficiency was performed but failed to reveal significant coding sequence changes.

Conclusions:
Our reverse discovery approach led to the identification of novel SF-1 targets and defined SOAT1 as an important factor in human adrenal steroidogenesis. SF-1–dependent up-regulation of SOAT1 may be important for maintaining readily-releasable cholesterol reserves needed for active steroidogenesis and during episodes of recurrent stress.
Asymmetric Aldol Reaction of Formaldehyde Catalyzed by Diarylprolinol
Authors: Yasui Yusuke , Benohoud Meryem , Sato Itaru , Hayashi Yujiro 
Published: January 2014

Abstract
The asymmetric cross-aldol reaction of formaldehyde with aldehyde pronucleophiles, catalyzed by trifluoromethyl-substituted diarylprolinol 1, was accomplished to directly afford α-hydroxymethyl-substituted aldehydes in good yield with excellent enantioselectivity.
Warming, soil moisture, and loss of snow increase Bromus tectorum’s population growth rate
Authors: Compagnoni Aldo , Adler Peter B. 
Published: January 2014

Abstract
Climate change threatens to exacerbate the impacts of invasive species. In temperate ecosystems, direct effects of warming may be compounded by dramatic reductions in winter snow cover. Cheatgrass (Bromus tectorum) is arguably the most destructive biological invader in basins of the North American Intermountain West, and warming could increase its performance through direct effects on demographic rates or through indirect effects mediated by loss of snow. We conducted a two-year experimental manipulation of temperature and snow pack to test whether 1) warming increases cheatgrass population growth rate and 2) reduced snow cover contributes to cheatgrass’ positive response to warming. We used infrared heaters operating continuously to create the warming treatment, but turned heaters on only during snowfalls for the snowmelt treatment. We monitored cheatgrass population growth rate and the vital rates that determine it: emergence, survival and fecundity. Growth rate increased in both warming and snowmelt treatments. The largest increases occurred in warming plots during the wettest year, indicating that the magnitude of response to warming depends on moisture availability. Warming increased both fecundity and survival, especially in the wet year, while snowmelt contributed to the positive effects of warming by increasing survival. Our results indicate that increasing temperature will exacerbate cheatgrass impacts, especially where warming causes large reductions in the depth and duration of snow cover.
Higher-Order Septin Assembly Is Driven by GTP-Promoted Conformational Changes: Evidence From Unbiased Mutational Analysis in Saccharomyces cerevisiae
Authors: Weems Andrew D , Johnson Courtney R , Argueso Juan Lucas , McMurray Michael A 
Published: January 2014

Abstract
Septin proteins bind GTP and heterooligomerize into filaments with conserved functions across a wide range of eukaryotes. Most septins hydrolyze GTP, altering the oligomerization interfaces; yet mutations designed to abolish nucleotide binding or hydrolysis by yeast septins perturb function only at high temperatures. Here, we apply an unbiased mutational approach to this problem. Mutations causing defects at high temperature mapped exclusively to the oligomerization interface encompassing the GTP-binding pocket, or to the pocket itself. Strikingly, cold-sensitive defects arise when certain of these same mutations are coexpressed with a wild-type allele, suggestive of a novel mode of dominance involving incompatibility between mutant and wild-type molecules at the septin–septin interfaces that mediate filament polymerization. A different cold-sensitive mutant harbors a substitution in an unstudied but highly conserved region of the septin Cdc12. A homologous domain in the small GTPase Ran allosterically regulates GTP-binding domain conformations, pointing to a possible new functional domain in some septins. Finally, we identify a mutation in septin Cdc3 that restores the high-temperature assembly competence of a mutant allele of septin Cdc10, likely by adopting a conformation more compatible with nucleotide-free Cdc10. Taken together, our findings demonstrate that GTP binding and hydrolysis promote, but are not required for, one-time events—presumably oligomerization-associated conformational changes—during assembly of the building blocks of septin filaments. Restrictive temperatures impose conformational constraints on mutant septin proteins, preventing new assembly and in certain cases destabilizing existing assemblies. These insights from yeast relate directly to disease-causing mutations in human septins.
In silico mining of microsatellites in coding sequences of the date palm (Arecaceae) genome, characterization, and transferability
Authors: Aberlenc‐Bertossi Frédérique , Castillo Karina , Tranchant‐Dubreuil Christine , Chérif Emira , Ballardini Marco , Abdoulkader Sabira , Gros‐Balthazard Muriel , Chabrillange Nathalie , Santoni Sylvain , Mercuri Antonio , Pintaud Jean‐Christophe 
Published: January 2014

• Premise of the study: To complement existing sets of primarily dinucleotide microsatellite loci from noncoding sequences of date palm, we developed primers for tri‐ and hexanucleotide microsatellite loci identified within genes. Due to their conserved genomic locations, the primers should be useful in other palm taxa, and their utility was tested in seven other Phoenix species and in Chamaerops, Livistona, and Hyphaene.• Methods and Results: Tandem repeat motifs of 3–6 bp were searched using a simple sequence repeat (SSR)–pipeline package in coding portions of the date palm draft genome sequence. Fifteen loci produced highly consistent amplification, intraspecific polymorphisms, and stepwise mutation patterns.• Conclusions: These microsatellite loci showed sufficient levels of variability and transferability to make them useful for population genetic, selection signature, and interspecific gene flow studies in Phoenix and other Coryphoideae genera.
Characterization of 13 microsatellite markers for Diuris basaltica (Orchidaceae) and related species
Authors: Ahrens Collin W. , James Elizabeth A. 
Published: January 2014

• Premise of the study: Diuris basaltica (Orchidaceae) is an endangered forb on the Victorian grasslands and has many close relatives. Microsatellite markers have been developed to facilitate assessment of population structure within D. basaltica and among related taxa within the species complex.• Methods and Results: Twenty‐five microsatellite markers (13 polymorphic and 12 monomorphic) were developed from D. basaltica using 454 pyrosequencing, and all primer pairs were amplified in D. gregaria and D. chryseopsis. For the set of polymorphic markers, the number of alleles per locus ranged from one to 10, two to nine, and two to 18 for D. basaltica, D. gregaria, and D. chryseopsis, respectively. The expected and observed heterozygosities ranged from 0.18 to 0.95 and 0.14 to 0.86, respectively.• Conclusions: The microsatellite markers developed in this study can be used to analyze the population genetic structure of D. basaltica and other Diuris species.
2matrix: A utility for indel coding and phylogenetic matrix concatenation1
Authors: Salinas Nelson R. , Little Damon P. 
Published: January 2014

• Premise of the study: Phylogenetic analysis of DNA and amino acid sequences requires the creation of files formatted specifically for each analysis package. Programs currently available cannot simultaneously code inferred insertion/deletion (indel) events in sequence alignments and concatenate data sets.• Methods and Results: A novel Perl script, 2matrix, was created to concatenate matrices of non‐molecular characters and/or aligned sequences and to code indels. 2matrix outputs a variety of formats compatible with popular phylogenetic programs.• Conclusions: 2matrix efficiently codes indels and concatenates matrices of sequences and non‐molecular data. It is available for free download under a GPL (General Public License) open source license (https://github.com/nrsalinas/2matrix/archive/master.zip).
Morphological Varieties of Soft Palate in Normal Individuals, Cleft Palate Patients and Obstructive Sleep Apnea Patients with Reference to Indian Population: A Preliminary Digital Cephalometric Study
Authors: Deepa V , Ramnarayan BK 
Published: January 2014

ABSTRACT

Objective
To identify the morphological varieties of the soft palate on a digital lateral cephalogram in the median sagittal plane which is presented variously in normal individuals with age and gender and also to assess if there exists any morphological variations in the soft palate among cleft palate and obstructive sleep apnea (OSA) groups.

Materials and methods
A total of 120 normal subjects, 15 cleft palate patients and 15 OSA patients, whose ages ranged from 5 years and above were included. The morphology of the soft palate on lateral cephalometry was examined and classified into different types. The dimensional differences of the soft palate between the types and the differences in proportion to different age and gender groups were also studied in normal individuals, cleft palate patients and OSA patients.

Results
The morphology of the soft palate was classified into six types with an additional ungrouped type. There was a significant increase in the length of soft palate with age. In cleft palate patients, the predominant type of soft palate was type 3 with shorter velar length, while the predominant type of soft palate in OSA patients was type 1 with the length of the soft palate longer than that of the normal group. No significant difference was observed between males and females with respect to the mean length in normal group, cleft palate group and OSA group.

Conclusion
Soft palate presents variable radiographic appearances on lateral cephalometry. The classic velar morphology in cleft palate and OSA patients serves as an alternative modality of investigation to identify the etiology at an earlier stage.

How to cite this article
Deepa V, David CM, Ramnarayan BK. Morphological Varieties of Soft Palate in Normal Individuals, Cleft Palate Patients and Obstructive Sleep Apnea Patients with Reference to Indian Population: A Preliminary Digital Cephalometric Study. World J Dent 2013;4(4):241-249.
Oceanic heat delivery via Kangerdlugssuaq Fjord to the south‐east Greenland ice sheet
Authors: Inall Mark E. , Murray Tavi , Cottier Finlo R. , Scharrer Kilian , Boyd Timothy J. , Heywood Karen J. , Bevan Suzanne L. 
Published: January 2014

AbstractAcceleration of the Greenland Ice Sheet (GrIS) tidewater outlet glaciers has increased the ice sheet's contribution to global sea level rise over the last two decades. Coincident increases in atmospheric temperatures around Greenland explain some of the increased ice loss, but warm Atlantic‐origin water (AW) is increasingly recognized as contributing to the accelerating ice‐mass loss, particularly, via the outlet glaciers of south‐east (SE) Greenland. However, there remains a lack of understanding of the variability in heat content of the water masses found to the east of Greenland and how this heat is communicated to the outlet glaciers of the GrIS. Here a new analysis is presented of ocean/GrIS interaction in which the oceanic heat flux toward the ice sheet in Kangerdlugssuaq Fjord (0.26 TW) is an order‐of‐magnitude greater than that reported for the other major outlet glacier of SE Greenland (Helheim). Heat delivered by AW to the calving front of Kangerdlugssuaq is equivalent to ∼10 m d−1 melt (i.e., 30–60% of the ice flow speed), and thus is highly significant. During the observational campaign in September 2010 warm Polar Surface Water (PSWw) melted a substantial volume of ice within the fjord; equivalent to 25% of the volume melted by AW alone. Satellite‐derived sea surface temperatures show large interannual variability in PSWw over the 20 year period 1991–2011. Anomalously warm PSWw was observed within the fjord prior to the well‐documented major ice front retreats of May 2004 and November 2010.
Impacts of canonical and Modoki El Niño on tropical Atlantic SST
Authors: Amaya Dillon J. , Foltz Gregory R. 
Published: January 2014

AbstractThe impacts of canonical and Modoki El Niño on tropical Atlantic sea surface temperature (SST) are quantified using composite analysis. Results show that El Niño Modoki fails to produce significant warming in the tropical Atlantic, in contrast to the well known warming following canonical El Niño events. El Niño Modoki instead induces significant cooling in the northeastern tropical Atlantic and near‐neutral conditions elsewhere in the tropical Atlantic. It is shown that the difference in SST response stems primarily from a much stronger Pacific/North American (PNA) teleconnection pattern and stronger atmospheric Kelvin wave response during canonical events compared to Modoki. The stronger PNA pattern and Kelvin waves during canonical events generate anomalously weak surface winds in the tropical North Atlantic, driving anomalously weak evaporative cooling and warmer SSTs. Past research has shown significant decadal variability in the frequency of noncanonical El Niños relative to canonical events. If such variability continues, it is likely that the impact of El Niño on tropical Atlantic SST will also fluctuate from one decade to the next.