bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diet and colorectal cancer: implications for the obese and devotees of the Atkins diet
Authors: Fleming M. E. , Sales K. M. , Winslet M. C. 
Published: February 2005

AbstractColorectal cancer (CRC) is the second most common cause of cancer‐related death in the Western world and its prevalence is increasing. Potential causes of this increase are changes in diet and the increases in obesity seen. This paper looks at the literature surrounding diet and obesity and the links to this increase in CRC. Heralded as a weight loss miracle we investigate whether the literature suggests the Atkins diet may actually do more harm than good by acting to increase an individual's risk of CRC. Obesity has been demonstrated to be a major factor in the increase in CRC although links to changes in diet are more tenuous. Published studies on diet suggest the Atkins diet may help reduce rather than increase the risk of CRC.
Pteridophyte richness, climate and topography in the Iberian Peninsula: comparing spatial and nonspatial models of richness patterns
Authors: Ferrer‐Castán Dolores , Vetaas Ole R. 
Published: February 2005

ABSTRACTAim  To describe the spatial variation in pteridophyte species richness; evaluate the importance of macroclimate, topography and within‐grid cell range variables; assess the influence of spatial autocorrelation on the significance of the variables; and to test the prediction of the mid‐domain effect.Location  The Iberian Peninsula.Methods  We estimated pteridophyte richness on a grid map with c. 2500 km2 cell size, using published geocoded data of the individual species. Environmental data were obtained by superimposing the grid system over isoline maps of precipitation, temperature, and altitude. Mean and range values were calculated for each cell. Pteridophyte richness was related to the environmental variables by means of nonspatial and spatial generalized least squares models. We also used ordinary least squares regression, where a variance partitioning was performed to partial out the spatial component, i.e. latitude and longitude. Coastal and central cells were compared to test the mid‐domain effect.Results  Both spatial and nonspatial models showed that pteridophyte richness was best explained by a second‐order polynomial of mean annual precipitation and a quadratic elevation‐range term, although the relative importance of these two variables varied when spatial autocorrelation was accounted for. Precipitation range was weakly significant in a nonspatial multiple model (i.e. ordinary regression), and did not remain significant in spatial models. Richness is significantly higher along the coast than in the centre of the peninsula.Main conclusions  Spatial autocorrelation affects the statistical significance of explanatory variables, but this did not change the biological interpretation of precipitation and elevation range as the main predictors of pteridophyte richness. Spatial and nonspatial models gave very similar results, which reinforce the idea that water availability and topographic relief control species richness in relatively high‐energy regions. The prediction of the mid‐domain effect is falsified.
Impact of short‐term rainfall fluctuation on interannual land cover change in sub‐Saharan Africa
Authors: Vanacker Veerle , Linderman Marc , Lupo Frederick , Flasse Stephanne , Lambin Eric 
Published: February 2005

ABSTRACTAim  Interannual land cover change plays a significant role in food security, ecosystem processes, and regional and global climate modelling. Measuring the magnitude and location and understanding the driving factors of interannual land cover change are therefore of utmost importance to improve our understanding and prediction of these impacts and to better differentiate between natural and human causes of land cover change. Despite advances in quantifying the magnitude of land cover change, the interpretation of the observed land cover change in terms of climatic, ecological and anthropogenic processes still remains a complex issue. In this paper, we map land cover change across sub‐Saharan Africa and examine the influences of rainfall fluctuations on interannual change.Location  The analysis was applied to sub‐Saharan Africa.Methods  Ten‐day rainfall estimates (RFE) obtained from National Oceanic and Atmospheric Administration's (NOAA) Climate Prediction Center (CPC) were used to extract information on inter and intra‐annual rainfall fluctuations. The magnitude of land cover change was quantified based on the multitemporal change vector method measuring year‐to‐year differences in bidirectional reflectance distribution function (BRDF) corrected 16‐day enhanced vegetation index (EVI) data from the Moderate Resolution Imaging Spectro‐radiometer (MODIS). Statistical models were used to estimate the relationship between short‐term rainfall variability and the magnitude of land cover change. The analysis was stratified first by physiognomic vegetation type and second by chorological data on species distribution to gain insights into spatial variations in response to short‐term rainfall fluctuations.Results  The magnitude of land cover change was significantly related to rainfall variability at the 5% level. Stratification considerably strengthened the relationship between the magnitude of change and rainfall variability. Explanatory power of the models ranged from R2 = 0.22 for the unstratified model to 0.40–0.96 for the individual models stratified by patterns of species distribution. The total variability explained by the combined models including the influence of rainfall and differences in vegetation response ranged from 22% for the model not stratified by vegetation to 76% when stratified by chorological data.Main conclusions  Using this methodology, we were able to measure the contribution of natural variation in precipitation to land cover change. Several ecosystems across sub‐Saharan Africa are highly sensitive to short‐term rainfall variability.
Allelic diversity at the Mhc‐DQA locus of woodmouse populations (Apodemus sylvaticus) present in the islands and mainland of the northern Mediterranean
Authors: De Bellocq Joëlle Goüy , Delarbre Christiane , Gachelin Gabriel , Morand Serge 
Published: February 2005

ABSTRACTAim Polymorphism at neutral markers and at MHC loci in rodent populations living on islands is generally low. The main genetic factors that may contribute to a reduced level of genetic variability are genetic drift, reduced gene flow and founder events. We investigated the pattern of polymorphism at the second exon of the Mhc‐DQA gene in island populations ofApodemus sylvaticusand in their mainland counterparts to investigate the pattern of MHC polymorphism in a phylogeographical context and to assess the impact of insularity on diversity at this locus.Location Eight north Mediterranean populations ofApodemus sylvaticuswere studied, including five island populations (Majorca, Minorca, Porquerolles, Port‐Cros and Sicily) and three mainland populations.Methods cDNA sequencing and nucleotide sequences analyses. Synonymous and non‐synonymous substitutions were examined at the PBR and non‐PBR sites. The DQA allelic distribution in populations was compared with the woodmouse phylogeography.Results This study presents novel DQA alleles. High polymorphism of the DQA locus is recorded in natural populations ofA. sylvaticuswith 13 alleles being widely distributed irrespective of the geographical origin and palaeoclimatic history of populations. The DQA locus does not show the expected pattern for non‐synonymous substitutions at the PBR sites. However, island populations show a weak loss of polymorphism in comparison with their mainland counterparts.Main conclusions The DQA locus in the woodmouse seems to be subject to weak selection and does not allow resolution of phylogeographical relationships among European woodmouse populations. The presence of at least three alleles in island populations and the maintenance of five alleles between the two European lineages over 1.5 Myr suggest that balancing selection may act within populations, and more precisely within island populations, to maintain genetic variability. This study shows that phylogeographical studies are a prerequisite for any genetic investigation of selected genes in natural populations.
Modelling geographical patterns in species richness using eigenvector‐based spatial filters
Authors: Diniz‐Filho José Alexandre Felizola , Bini Luis Mauricio 
Published: February 2005

ABSTRACTAim  To test the mechanisms driving bird species richness at broad spatial scales using eigenvector‐based spatial filtering.Location  South America.Methods  An eigenvector‐based spatial filtering was applied to evaluate spatial patterns in South American bird species richness, taking into account spatial autocorrelation in the data. The method consists of using the geographical coordinates of a region, based on eigenanalyses of geographical distances, to establish a set of spatial filters (eigenvectors) expressing the spatial structure of the region at different spatial scales. These filters can then be used as predictors in multiple and partial regression analyses, taking into account spatial autocorrelation. Autocorrelation in filters and in the regression residuals can be used as stopping rules to define which filters will be used in the analyses.Results  Environmental component alone explained 8% of variation in richness, whereas 77% of the variation could be attributed to an interaction between environment and geography expressed by the filters (which include mainly broad‐scale climatic factors). Regression coefficients of environmental component were highest for AET. These results were unbiased by short‐scale spatial autocorrelation. Also, there was a significant interaction between topographic heterogeneity and minimum temperature.Conclusion  Eigenvector‐based spatial filtering is a simple and suitable statistical protocol that can be used to analyse patterns in species richness taking into account spatial autocorrelation at different spatial scales. The results for South American birds are consistent with the climatic hypothesis, in general, and energy hypothesis, in particular. Habitat heterogeneity also has a significant effect on variation in species richness in warm tropical regions.
FLT3-ITD and tyrosine kinase domain mutants induce 2 distinct phenotypes in a murine bone marrow transplantation model
Authors: Grundler Rebekka , Miething Cornelius , Thiede Christian , Peschel Christian , Duyster Justus 
Published: February 2005

Abstract
Activating mutations of the Fms-like tyrosine kinase 3 (FLT3) receptor are the most common genetic alteration in acute myeloid leukemia (AML). Two distinct groups of FLT3 mutations are found: internal tandem duplications (ITDs) of the juxtamembrane region and point mutations within the tyrosine kinase domain (TKD). Recently, point mutations within the activation loop of FLT3 have also been described in childhood acute lymphoblastic leukemia (ALL). FLT3-ITD has been shown to induce a myeloproliferative syndrome in a murine bone marrow transplantation model. The phenotype of FLT3-TKD in mice has not yet been investigated. We transduced murine bone marrow with retrovirus-expressing FLT3-TKD mutants or FLT3-ITD and transplanted these cells into lethally irradiated mice. Mice that received a transplant of FLT3-ITD developed an oligoclonal myeloproliferative disease as previously described. In contrast, FLT3-TKD mutants induced an oligoclonal lymphoid disorder with longer latency and distinct hematologic manifestations: importantly, induction of the lymphoid phenotype was not due to a low number of transplanted cells. The lymphoid manifestation and longer latency of FLT3-TKD compared with FLT3-ITD mutants together with the lack of influence of FLT3-TKD mutations on the clinical outcome of patients with AML suggest differences in cell signaling between FLT3-TKD mutants and FLT3-ITDs. Indeed strong signal transducers and activators of transcription 5 (STAT5) activation could only be demonstrated for FLT3-ITDs. (Blood. 2005;105:4792-4799)
Contribution of gap junctional communication between tumor cells and astroglia to the invasion of the brain parenchyma by human glioblastomas
Authors: Oliveira Roxane , Christov Christo , Guillamo Jean Sébastien , de Boüard Sophie , Palfi Stéphane , Venance Laurent , Tardy Marcienne , Peschanski Marc 
Published: February 2005

Abstract
Background
Gliomas are "intraparenchymally metastatic" tumors, invading the brain in a non-destructive way that suggests cooperation between glioma cells and their environment. Recent studies using an engineered rodent C6 tumor cell line have pointed to mechanisms of invasion that involved gap junctional communication (GJC), with connexin 43 as a substrate. We explored whether this concept may have clinical relevance by analyzing the participation of GJC in human glioblastoma invasion.

Results
Three complementary in vitro assays were used: (i) seeding on collagen IV, to analyze homocellular interactions between tumor cells (ii) co-cultures with astrocytes, to study glioblastoma/astrocytes relationships and (iii) implantation into organotypic brain slice cultures, that mimic the three-dimensional parenchymal environment. Carbenoxolone, a potent blocker of GJC, inhibited cell migration in the two latter models. It paradoxically increased it in the first one. These results showed that homocellular interaction between tumor cells supports intercellular adhesion, whereas heterocellular glioblastoma/astrocytes interactions through functional GJC conversely support tumor cell migration. As demonstrated for the rodent cell line, connexin 43 may be responsible for this heterocellular functional coupling. Its levels of expression, high in astrocytes, correlated positively with invasiveness in biopsied tumors.

Conclusions
our results underscore the potential clinical relevance of the concept put forward by other authors based on experiments with a rodent cell line, that glioblastoma cells use astrocytes as a substrate for their migration by subverting communication through connexin 43-dependent gap junctions.
Novel hepatocyte growth factor (HGF) binding domains on fibronectin and vitronectin coordinate a distinct and amplified Met-integrin induced signalling pathway in endothelial cells
Authors: Rahman Salman , Patel Yatin , Murray Jacqueline , Patel Kirti V , Sumathipala Rushika , Sobel Michael , Wijelath Errol S 
Published: February 2005

Abstract
Background
The growth of new blood vessels in adult life requires the initiation of endothelial cell migration and proliferation from pre-existing vessels in addition to the recruitment and differentiation of circulating endothelial progenitor cells. Signals emanating from growth factors and the extracellular matrix are important in regulating these processes.

Results
Here we report that fibronectin (FN) and vitronectin (VN) modulate the responses of endothelial cells to HGF (Scatter Factor), an important pro-angiogenic mediator. Novel binding sites for HGF were identified on both FN and VN that generate molecular complexes with enhanced biological activity and these were identified in the supernatants of degranulated platelet suspensions implicating their release and formation in vivo. In the absence of co-stimulation with an ECM glycoprotein, HGF could not promote endothelial cell migration but retained the capacity to induce a proliferative response utilising the Map kinase pathway. Through promoting Met-Integrin association, HGF-FN and HGF-VN complexes coordinated and enhanced endothelial cell migration through activation of the PI-3 kinase pathway involving a Ras-dependent mechanism whereas a Ras-independent and attenuated migratory response was promoted by co-stimulation of cells with HGF and a non-binding partner ECM glycoprotein such as collagen-1.

Conclusions
These studies identify a novel mechanism and pathway of HGF signalling in endothelial cells involving cooperation between Met and integrins in a Ras dependent manner. These findings have implications for the regulation of neovascularization in both health and disease.
An interactional network of genes involved in chitin synthesis in Saccharomyces cerevisiae
Authors: Lesage Guillaume , Shapiro Jesse , Specht Charles A , Sdicu Anne-Marie , Ménard Patrice , Hussein Shamiza , Tong Amy Hin Yan , Boone Charles , Bussey Howard 
Published: February 2005

Abstract
Background
In S. cerevisiae the β-1,4-linked N-acetylglucosamine polymer, chitin, is synthesized by a family of 3 specialized but interacting chitin synthases encoded by CHS1, CHS2 and CHS3. Chs2p makes chitin in the primary septum, while Chs3p makes chitin in the lateral cell wall and in the bud neck, and can partially compensate for the lack of Chs2p. Chs3p requires a pathway of Bni4p, Chs4p, Chs5p, Chs6p and Chs7p for its localization and activity. Chs1p is thought to have a septum repair function after cell separation. To further explore interactions in the chitin synthase family and to find processes buffering chitin synthesis, we compiled a genetic interaction network of genes showing synthetic interactions with CHS1, CHS3 and genes involved in Chs3p localization and function and made a phenotypic analysis of their mutants.

Results
Using deletion mutants in CHS1, CHS3, CHS4, CHS5, CHS6, CHS7 and BNI4 in a synthetic genetic array analysis we assembled a network of 316 interactions among 163 genes. The interaction network with CHS3, CHS4, CHS5, CHS6, CHS7 or BNI4 forms a dense neighborhood, with many genes functioning in cell wall assembly or polarized secretion. Chitin levels were altered in 54 of the mutants in individually deleted genes, indicating a functional relationship between them and chitin synthesis. 32 of these mutants triggered the chitin stress response, with elevated chitin levels and a dependence on CHS3. A large fraction of the CHS1-interaction set was distinct from that of the CHS3 network, indicating broad roles for Chs1p in buffering both Chs2p function and more global cell wall robustness.

Conclusion
Based on their interaction patterns and chitin levels we group interacting mutants into functional categories. Genes interacting with CHS3 are involved in the amelioration of cell wall defects and in septum or bud neck chitin synthesis, and we newly assign a number of genes to these functions. Our genetic analysis of genes not interacting with CHS3 indicate expanded roles for Chs4p, Chs5p and Chs6p in secretory protein trafficking and of Bni4p in bud neck organization.
Identification of functional SNPs in the 5-prime flanking sequences of human genes
Authors: Mottagui-Tabar Salim , Faghihi Mohammad A , Mizuno Yosuke , Engström Pär G , Lenhard Boris , Wasserman Wyeth W , Wahlestedt Claes 
Published: February 2005

Abstract
Background
Over 4 million single nucleotide polymorphisms (SNPs) are currently reported to exist within the human genome. Only a small fraction of these SNPs alter gene function or expression, and therefore might be associated with a cell phenotype. These functional SNPs are consequently important in understanding human health. Information related to functional SNPs in candidate disease genes is critical for cost effective genetic association studies, which attempt to understand the genetics of complex diseases like diabetes, Alzheimer's, etc. Robust methods for the identification of functional SNPs are therefore crucial. We report one such experimental approach.

Results
Sequence conserved between mouse and human genomes, within 5 kilobases of the 5-prime end of 176 GPCR genes, were screened for SNPs. Sequences flanking these SNPs were scored for transcription factor binding sites. Allelic pairs resulting in a significant score difference were predicted to influence the binding of transcription factors (TFs). Ten such SNPs were selected for mobility shift assays (EMSA), resulting in 7 of them exhibiting a reproducible shift. The full-length promoter regions with 4 of the 7 SNPs were cloned in a Luciferase based plasmid reporter system. Two out of the 4 SNPs exhibited differential promoter activity in several human cell lines.

Conclusions
We propose a method for effective selection of functional, regulatory SNPs that are located in evolutionary conserved 5-prime flanking regions (5'-FR) regions of human genes and influence the activity of the transcriptional regulatory region. Some SNPs behave differently in different cell types.
The PECACE domain: a new family of enzymes with potential peptidoglycan cleavage activity in Gram-positive bacteria
Authors: Pagliero Estelle , Dideberg Otto , Vernet Thierry , Di Guilmi Anne Marie 
Published: February 2005

Abstract
Background
The metabolism of bacterial peptidoglycan is a dynamic process, synthases and cleavage enzymes are functionally coordinated. Lytic Transglycosylase enzymes (LT) are part of multienzyme complexes which regulate bacterial division and elongation. LTs are also involved in peptidoglycan turnover and in macromolecular transport systems. Despite their central importance, no LTs have been identified in the human pathogen Streptococcus pneumoniae. We report the identification of the first putative LT enzyme in S. pneumoniae and discuss its role in pneumococcal peptidoglycan metabolism.

Results
Homology searches of the pneumococcal genome allowed the identification of a new domain putatively involved in peptidoglycan cleavage (PECACE, PE ptidoglycan CA rbohydrate C leavage E nzyme). This sequence has been found exclusively in Gram-positive bacteria and gene clusters containing pecace are conserved among Streptococcal species. The PECACE domain is, in some instances, found in association with other domains known to catalyze peptidoglycan hydrolysis.

Conclusions
A new domain, PECACE, putatively involved in peptidoglycan hydrolysis has been identified in S. pneumoniae. The probable enzymatic activity deduced from the detailed analysis of the amino acid sequence suggests that the PECACE domain may proceed through a LT-type or goose lyzosyme-type cleavage mechanism. The PECACE function may differ largely from the other hydrolases already identified in the pneumococcus: LytA, LytB, LytC, CBPD and PcsB. The multimodular architecture of proteins containing the PECACE domain is another example of the many activities harbored by peptidoglycan hydrolases, which is probably required for the regulation of peptidoglycan metabolism. The release of new bacterial genomes sequences will probably add new members to the five groups identified so far in this work, and new groups could also emerge. Conversely, the functional characterization of the unknown domains mentioned in this work can now become easier, since bacterial peptidoglycan is proposed to be the substrate.