bluuebunny/crossref_metadata_2025 huggingface dataset:
Linkage Maps of thedwarfand Normal Lake Whitefish (Coregonus clupeaformis) Species Complex and Their Hybrids Reveal the Genetic Architecture of Population Divergence
Authors: Rogers S M , Isabel N , Bernatchez L
Published: November 2006

Elucidating the genetic architecture of population divergence may reveal the evolution of reproductive barriers and the genomic regions implicated in the process. We assembled genetic linkage maps for the dwarf and Normal lake whitefish species complex and their hybrids. A total of 877 AFLP loci and 30 microsatellites were positioned. The homology of mapped loci between families supported the existence of 34 linkage groups (of 40n expected) exhibiting 83% colinearity among linked loci between these two families. Classes of AFLP markers were not randomly distributed among linkage groups. Both AFLP and microsatellites exhibited deviations from Mendelian expectations, with 30.4% exhibiting significant segregation distortion across 28 linkage groups of the four linkage maps in both families (P < 0.00001). Eight loci distributed over seven homologous linkage groups were significantly distorted in both families and the level of distortion, when comparing homologous loci of the same phase between families, was correlated (Spearman R = 0.378, P = 0.0021). These results suggest that substantial divergence incurred during allopatric glacial separation and subsequent sympatric ecological specialization has resulted in several genomic regions that are no longer complementary between dwarf and Normal populations issued from different evolutionary glacial lineages.
Genes Affecting Cell Competition in Drosophila
Authors: Tyler David M , Li Wei , Zhuo Ning , Pellock Brett , Baker Nicholas E
Published: November 2006

Cell competition is a homeostatic mechanism that regulates the size attained by growing tissues. We performed an unbiased genetic screen for mutations that permit the survival of cells being competed due to haplo-insufficiency for RpL36. Mutations that protect RpL36 heterozygous clones include the tumor suppressors expanded, hippo, salvador, mats, and warts, which are members of the Warts pathway, the tumor suppressor fat, and a novel tumor-suppressor mutation. Other hyperplastic or neoplastic mutations did not rescue RpL36 heterozygous clones. Most mutations that rescue cell competition elevated Dpp-signaling activity, and the Dsmurf mutation that elevates Dpp signaling was also hyperplastic and rescued. Two nonlethal, nonhyperplastic mutations prevent the apoptosis of Minute heterozygous cells and suggest an apoptosis pathway for cell competition . In addition to rescuing RpL36 heterozygous cells, mutations in Warts pathway genes were supercompetitors that could eliminate wild-type cells nearby. The findings show that differences in Warts pathway activity can lead to competition and implicate the Warts pathway, certain other tumor suppressors, and novel cell death components in cell competition, in addition to the Dpp pathway implicated by previous studies. We suggest that cell competition might occur during tumor development in mammals.
Antagonizing Scalloped With a Novel Vestigial Construct Reveals an Important Role for Scalloped in Drosophila melanogaster Leg, Eye and Optic Lobe Development
Authors: Garg Ankush , Srivastava Ajay , Davis Monica M , O'Keefe Sandra L , Chow Leola , Bell John B
Published: November 2006

Scalloped (SD), a TEA/ATTS-domain-containing protein, is required for the proper development of Drosophila melanogaster. Despite being expressed in a variety of tissues, most of the work on SD has been restricted to understanding its role and function in patterning the adult wing. To gain a better understanding of its role in development, we generated sd47M flip-in mitotic clones. The mitotic clones had developmental defects in the leg and eye. Further, by removing the VG domains involved in activation, we created a reagent (VGΔACT) that disrupts the ability of SD to form a functional transcription factor complex and produced similar phenotypes to the flip-in mitotic clones. The VGΔACT construct also disrupted adult CNS development. Expression of the VGΔACT construct in the wing alters the cellular localization of VG and produces a mutant phenotype, indicating that the construct is able to antagonize the normal function of the SD/VG complex. Expression of the protein:protein interaction portion of SD is also able to elicit similar phenotypes, suggesting that SD interacts with other cofactors in the leg, eye, and adult CNS. Furthermore, antagonizing SD in larval tissues results in cell death, indicating that SD may also have a role in cell survival.
Nearly Identical Paralogs: Implications for Maize (Zea mays L.) Genome Evolution
Authors: Emrich Scott J , Li Li , Wen Tsui-Jung , Yandeau-Nelson Marna D , Fu Yan , Guo Ling , Chou Hui-Hsien , Aluru Srinivas , Ashlock Daniel A , Schnable Patrick S
Published: November 2006

As an ancient segmental tetraploid, the maize (Zea mays L.) genome contains large numbers of paralogs that are expected to have diverged by a minimum of 10% over time. Nearly identical paralogs (NIPs) are defined as paralogous genes that exhibit ≥98% identity. Sequence analyses of the “gene space” of the maize inbred line B73 genome, coupled with wet lab validation, have revealed that, conservatively, at least ∼1% of maize genes have a NIP, a rate substantially higher than that in Arabidopsis. In most instances, both members of maize NIP pairs are expressed and are therefore at least potentially functional. Of evolutionary significance, members of many NIP families also exhibit differential expression. The finding that some families of maize NIPs are closely linked genetically while others are genetically unlinked is consistent with multiple modes of origin. NIPs provide a mechanism for the maize genome to circumvent the inherent limitation that diploid genomes can carry at most two “alleles” per “locus.” As such, NIPs may have played important roles during the evolution and domestication of maize and may contribute to the success of long-term selection experiments in this important crop species.
Mutations Leading to Loss of Sporulation Ability in Bacillus subtilis Are Sufficiently Frequent to Favor Genetic Canalization
Authors: Masel Joanna , Maughan Heather
Published: November 2006

We measured the rate of mutations impairing sporulation ability in Bacillus subtilis as 0.003 in a mutator population, following 6000 generations of strong selection for sporulation that have previously been described. This means that the product of the population size and the functional mutation rate is ∼105, well within the parameter range for which genetic canalization of sporulation ability is expected.
Temporal Estimates of Effective Population Size in Species With Overlapping Generations
Authors: Waples Robin S , Yokota Masashi
Published: November 2006

The standard temporal method for estimating effective population size (Ne) assumes that generations are discrete, but it is routinely applied to species with overlapping generations. We evaluated bias in the estimates $\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \({\hat{N}}_{\mathrm{e}}\) \end{document}$ caused by violation of this assumption, using simulated data for three model species: humans (type I survival), sparrow (type II), and barnacle (type III). We verify a previous proposal by Felsenstein that weighting individuals by reproductive value is the correct way to calculate parametric population allele frequencies, in which case the rate of change in age-structured populations conforms to that predicted by discrete-generation models. When the standard temporal method is applied to age-structured species, typical sampling regimes (sampling only newborns or adults; randomly sampling the entire population) do not yield properly weighted allele frequencies and result in biased $\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \({\hat{N}}_{\mathrm{e}}\) \end{document}$. The direction and magnitude of the bias are shown to depend on the sampling method and the species' life history. Results for populations that grow (or decline) at a constant rate paralleled those for populations of constant size. If sufficient demographic data are available and certain sampling restrictions are met, the Jorde–Ryman modification of the temporal method can be applied to any species with overlapping generations. Alternatively, spacing the temporal samples many generations apart maximizes the drift signal compared to sampling biases associated with age structure.
An Ectopic Expression Screen Reveals the Protective and Toxic Effects of Drosophila Seminal Fluid Proteins
Authors: Mueller Jacob L , Page Jennifer L , Wolfner Mariana F
Published: November 2006

In Drosophila melanogaster, seminal fluid regulates the reproductive and immune responses of mated females. Some seminal fluid proteins may provide protective functions to mated females, such as antimicrobial activity and/or stimulation of antimicrobial gene expression levels, while others appear to have negative effects, contributing to a “cost of mating.” To identify seminal proteins that could participate in these phenomena, we used a systemic ectopic expression screen to test the effects on unmated females of proteins normally produced by the male accessory gland (Acps). Of the 21 ectopically expressed Acps that we tested for ability to assist in the clearance of a bacterial infection with Serratia marcescens, 3 Acps significantly reduced the bacterial counts of infected females, suggesting a protective role. Of the 23 Acps that we tested for toxicity, 3 were toxic, including one that has been implicated in the cost of mating in another study. We also tested ectopic expression females for other Acp-induced effects, but found no additional Acps that affected egg laying or receptivity upon ectopic expression.
Cytogenetic and Molecular Characterization of Heterochromatin Gene Models in Drosophila melanogaster
Authors: Rossi Fabrizio , Moschetti Roberta , Caizzi Ruggiero , Corradini Nicoletta , Dimitri Patrizio
Published: November 2006

In the past decade, genome-sequencing projects have yielded a great amount of information on DNA sequences in several organisms. The release of the Drosophila melanogaster heterochromatin sequence by the Drosophila Heterochromatin Genome Project (DHGP) has greatly facilitated studies of mapping, molecular organization, and function of genes located in pericentromeric heterochromatin. Surprisingly, genome annotation has predicted at least 450 heterochromatic gene models, a figure 10-fold above that defined by genetic analysis. To gain further insight into the locations and functions of D. melanogaster heterochromatic genes and genome organization, we have FISH mapped 41 gene models relative to the stained bands of mitotic chromosomes and the proximal divisions of polytene chromosomes. These genes are contained in eight large scaffolds, which together account for ∼1.4 Mb of heterochromatic DNA sequence. Moreover, developmental Northern analysis showed that the expression of 15 heterochromatic gene models tested is similar to that of the vital heterochromatic gene Nipped-A, in that it is not limited to specific stages, but is present throughout all development, despite its location in a supposedly “silent” region of the genome. This result is consistent with the idea that genes resident in heterochromatin can encode essential functions.
Chi Hotspot Activity in Escherichia coli Without RecBCD Exonuclease Activity: Implications for the Mechanism of Recombination
Authors: Amundsen Susan K , Smith Gerald R
Published: November 2006

The major pathway of genetic recombination and DNA break repair in Escherichia coli requires RecBCD enzyme, a complex nuclease and DNA helicase regulated by Chi sites (5′-GCTGGTGG-3′). During its unwinding of DNA containing Chi, purified RecBCD enzyme has two alternative nucleolytic reactions, depending on the reaction conditions: simple nicking of the Chi-containing strand at Chi or switching of nucleolytic degradation from the Chi-containing strand to its complement at Chi. We describe a set of recC mutants with a novel intracellular phenotype: retention of Chi hotspot activity in genetic crosses but loss of detectable nucleolytic degradation as judged by the growth of mutant T4 and λ phages and by assay of cell-free extracts. We conclude that RecBCD enzyme's nucleolytic degradation of DNA is not necessary for intracellular Chi hotspot activity and that nicking of DNA by RecBCD enzyme at Chi is sufficient. We discuss the bearing of these results on current models of RecBCD pathway recombination.
The Saccharomyces cerevisiae ATP22 Gene Codes for the Mitochondrial ATPase Subunit 6-Specific Translation Factor
Authors: Zeng Xiaomei , Hourset Audrey , Tzagoloff Alexander
Published: November 2006

Mutations in the Saccharomyces cerevisiae ATP22 gene were previously shown to block assembly of the F0 component of the mitochondrial proton-translocating ATPase. Further inquiries into the function of Atp22p have revealed that it is essential for translation of subunit 6 of the mitochondrial ATPase. The mutant phenotype can be partially rescued by the presence in the same cell of wild-type mitochondrial DNA and a ρ− deletion genome in which the 5′-UTR, first exon, and first intron of COX1 are fused to the fourth codon of ATP6. The COX1/ATP6 gene is transcribed and processed to the mature mRNA by splicing of the COX1 intron from the precursor. The hybrid protein translated from the novel mRNA is proteolytically cleaved at the normal site between residues 10 and 11 of the subunit 6 precursor, causing the release of the polypeptide encoded by the COX1 exon. The ability of the ρ− suppressor genome to express subunit 6 in an atp22 null mutant constitutes strong evidence that translation of subunit 6 depends on the interaction of Atp22p with the 5′-UTR of the ATP6 mRNA.
Accumulation of Deleterious Mutations in Small Abiotic Populations of RNA
Authors: Soll Steven J , Arenas Carolina Díaz , Lehman Niles
Published: November 2006

The accumulation of slightly deleterious mutations in populations leads to the buildup of a genetic load and can cause the extinction of populations of small size. Mutation-accumulation experiments have been used to study this process in a wide variety of organisms, yet the exact mutational underpinnings of genetic loads and their fitness consequences remain poorly characterized. Here, we use an abiotic system of RNA populations evolving continuously in vitro to examine the molecular events that can instigate a genetic load. By tracking the fitness decline of ligase ribozyme populations with bottleneck sizes between 100 and 3000 molecules, we detected the appearance and subsequent fixation of both slightly deleterious mutations and advantageous mutations. Smaller populations went extinct in significantly fewer generations than did larger ones, supporting the notion of a mutational meltdown. These data suggest that mutation accumulation was an important evolutionary force in the prebiotic RNA world and that mechanisms such as recombination to ameliorate genetic loads may have been in place early in the history of life.
Teaching How to Prepare a Manuscript by Means of Rewriting Published Scientific Papers
Authors: Tomaska Lubomir
Published: November 2006

The objective of the course described here is to train undergraduate students to write a scientific manuscript. The students participate in selection of a current topic in contemporary genetics or molecular biology by choosing the most interesting paper of a given year. After the teacher provides all essential background about the selected subject, he or she selects a recent article from the corresponding field and presents the students with all the necessary information contained in the paper without revealing its title and author. The data presented in the paper are reviewed by the class so that each student understands every experiment and the main points of the work. Simultaneously, the students are informed about the basic rules of writing the individual sections of a scientific paper. They are then asked to write and formally submit a manuscript summarizing the data. Finally, the students act as reviewers of their colleagues' manuscripts and compare their papers with the original published articles. This enables them to identify both the strengths and the weaknesses of their manuscripts and to gain confidence in the writing skills that will be so critical for their future scientific activities.
A Modified Algorithm for the Improvement of Composite Interval Mapping
Authors: Li Huihui , Ye Guoyou , Wang Jiankang
Published: November 2006

Composite interval mapping (CIM) is the most commonly used method for mapping quantitative trait loci (QTL) with populations derived from biparental crosses. However, the algorithm implemented in the popular QTL Cartographer software may not completely ensure all its advantageous properties. In addition, different background marker selection methods may give very different mapping results, and the nature of the preferred method is not clear. A modified algorithm called inclusive composite interval mapping (ICIM) is proposed in this article. In ICIM, marker selection is conducted only once through stepwise regression by considering all marker information simultaneously, and the phenotypic values are then adjusted by all markers retained in the regression equation except the two markers flanking the current mapping interval. The adjusted phenotypic values are finally used in interval mapping (IM). The modified algorithm has a simpler form than that used in CIM, but a faster convergence speed. ICIM retains all advantages of CIM over IM and avoids the possible increase of sampling variance and the complicated background marker selection process in CIM. Extensive simulations using two genomes and various genetic models indicated that ICIM has increased detection power, a reduced false detection rate, and less biased estimates of QTL effects.
The Membrane‐Bound Lon Protease from Thermoplasma Displays Unfolding Activity
Authors: Besche Henrike , Navon Amiel , Zwickl Peter
Published: November 2006

The membrane‐bound Lon protease from Thermoplasma acidophilum (Ta Lon) was shown to unfold and degrade a fusion of the green fluorescent protein with calmodulin (GFP—CaM). Unfolding and degradation were ATP‐dependent reactions and could be inhibited by calcium ions, which are known to stabilize calmodulin. Notably, an inverse fusion of the same proteins, i.e., CaM—GFP, as well as GFP or GFP‐SsrA, was neither unfolded nor degraded. Thus, Ta Lon seems to unfold and degrade preferentially protein substrates with an extended unstructured C‐terminus. A set of Ta Lon variants mutated in critical residues of the AAA+ domain, were tested for their respective ATPase and GFP—CaM unfolding activity. This analysis revealed that the rate of ATP hydrolysis correlated with the efficiency of the GFP—CaM unfolding activity. In summary, we show here that the membrane‐bound Ta Lon protease displays an unfolding activity, which is correlated with the rate of ATP hydrolysis.
The E3 Ubiquitin Ligases HRD1 and SCFFbs2 Recognize the Protein Moiety and Sugar Chains, Respectively, of an ER‐Associated Degradation Substrate
Authors: Groisman Bella , Avezov Edward , Lederkremer Gerardo Z.
Published: November 2006

Several E3 ubiquitin ligases have been identified that participate in endoplasmic reticulum‐associated degradation (ERAD) of misfolded membrane and secretory proteins. Sometimes two ligases were shown to share the same substrate. However, it is not known whether they recognize the same structural determinants and constitute alternative pathways for ubiquitination or if they can act sequentially on different determinants on the substrate. Here we have analyzed in cells in vivo interactions of the recently identified mammalian HRD1 and SCFFbs2 with a model ERAD substrate, uncleaved precursor of asialoglycoprotein receptor H2a, and their involvement in its degradation. As Fbs2 had been shown to bind sugar chains, we studied the influence of glycosylation of the substrate by analyzing the effect of dominant negative mutants of HRD1 and Fbs2 on ERAD of H2a and of a mutant lacking all three of its glycosylation sites. Both HRD1 and Fbs2 were found to associate with H2a, and their mutants inhibited its degradation, but only dominant negative HRD1 blocked the degradation of the unglycosylated version of H2a.

This suggests a cooperative action of the two ligases that target the glycans (Fbs2) and a protein motif (HRD1). In addition, our results suggest the need for retrotranslocation of the luminal glycosylated domain of the substrate prior to interaction with cytosolic Fbs2.
The Origins of the Ubiquitin Field
Authors: Varshavsky Alexander
Published: November 2006

This is a personal account of the early history of ubiquitin research by one of its protagonists. The field of ubiquitin and regulated protein degradation was created in the 1980s, largely through the complementary discoveries by the laboratory of A. Hershko (Technion, Haifa, Israel) and by my laboratory, then at MIT (Cambridge, MA, USA). I describe the elegant insights by Hershko and his colleagues that yielded the initial understanding of the chemistry of ubiquitin conjugation and ubiquitin‐mediated proteolysis in cell extracts, including the identifcation of E1, E2, and E3 enzymes. These advances were followed by a set of interconnected discoveries in my laboratory that revealed the biology of the ubiquitin system, i.e., its necessity for protein degradation in vivo, its specific physiological functions (in the cell cycle, DNA repair, protein synthesis, transcriptional regulation, and stress responses), the source of its selectivity (specific degradation signals in short‐lived proteins), and its key mechanistic attributes, such as the polyubiquitin chain and the subunit selectivity of protein degradation. The above biological (function‐based) insights produced the main discovery of the physiological regulation by intracellular protein degradation. These advances caused the enormous expansion of the ubiquitin field in the 1990s. Together with the initial discovery of ubiquitin‐mediated proteolysis by Hershko and coworkers, our biological discoveries in the 1980s led to a radically changed understanding of the logic of intracellular circuits, as it became clear that the control through regulated protein degradation rivals, and often surpasses in significance, the classical regulation through transcription and translation.
Multiple Forms of the 26S Proteasome‐Associated Protein Ecm29 in the Mouse Brain
Authors: Gorbea Carlos , Kaufmann Anthony G. , Pratt Gregory , Rechsteiner Martin , Rogers Scott W.
Published: November 2006

Ecm29 is an ˜200‐K HEAT‐repeat protein that associates with the 26S proteasome in yeast and HeLa cells. Whereas in most mouse organs Ecm29 is present as a single 200‐K protein, in the brain there are eleven species, ranging from 55 K to greater than 250 K, that react with anti‐Ecm29 antibodies. Since the largest brain‐specific Ecm29 variant reacts with antibodies to sequences within the N‐terminal and C‐terminal regions of the protein, but not to the antibody directed to its central region, this putative isoform likely arises by alternative splicing. Some of the smaller Ecm29‐positive forms appear to arise by proteolytic processing, but extraction of minced brain fragments in boiling SDS‐PAGE sample buffer reveals that all forms are present prior to homogenization. Only the 220‐K Ecm29 species is clearly associated with the 26S proteasome; with one exception, the other variants sediment slower than 20S. Direct dissection and immunohistochemistry reveal that these putative Ecm29 isoforms are present throughout the central nervous system. However, anti‐Ecm29 immunoreactivity is differentially distributed within subregions of the mouse brain and among cell types, suggesting that Ecm29 isoform distribution contributes to the complexity and regional specificity of brain function.
Characterization and Purification of Kinase Activities against Arabidopsis COP9 Signalosome Subunit 7
Authors: Malec Przemyslaw , Chamovitz Daniel A.
Published: November 2006

The COP9 signalosome (CSN) is a multisubunit protein complex that intersects the ubiquitin (Ub)–proteasome pathway at several junctions. The CSN associates with several protein kinases that target key regulatory proteins that themselves are targets for Ub‐dependent degradation, and several subunits themselves are phosphoproteins. We previously reported that Arabidopsis CSN7 is a phosphoprotein. To identify the kinases responsible for CSN7 phosphorylation, we biochemically purified CSN7‐kinsae activities from cauliflower through a four‐step purification procedure that resulted in a ca. 300‐fold enrichment. One of these activities is Ca2+ dependent, while the second is not. Peptide fingerprint analysis of the purified proteins identified three putative CSN7 kinases.
Lost Watersheds: Barriers, Aquatic Habitat Connectivity, and Salmon Persistence in the Willamette and Lower Columbia River Basins
Authors: Sheer M. B. , Steel E. A.
Published: November 2006

Large portions of watersheds and streams are lost to anadromous fishes because of anthropogenic barriers to migration. The loss of these streams and rivers has shifted the distribution of accessible habitat, often reducing the diversity of accessible habitat and the quantity of high‐quality habitat. We combined existing inventories of barriers to adult fish passage in the Willamette and Lower Columbia River basins and identified 1,491 anthropogenic barriers to fish passage blocking 14,931 km of streams. We quantified and compared the stream quality, land cover, and physical characteristics of lost versus currently accessible habitat by watershed, assessed the effect of barriers on the variability of accessible habitats, and investigated potential impacts of habitat reduction on endangered or threatened salmonid populations. The majority of the study watersheds have lost more than 40% of total fish stream habitat. Overall, 40% of the streams with spawning gradients suitable for steelhead (anadromous rainbow trout Oncorhynchus mykiss), 60% of streams with riparian habitat in good condition, and 30% of streams draining watersheds with all coniferous land cover are no longer accessible to anadromous fish. Across watersheds, hydrologic and topographic watershed characteristics were correlated with barrier location, barrier density, and the impacts of barriers on habitat. Population‐based abundance scores for spring Chinook salmon O. tshawytscha were strongly correlated with the magnitude of habitat lost and the number of lowland fish passage barriers. The characteristics of barrier and habitat distribution presented in this paper indicate that barrier removal projects and mitigation for instream barriers should consider both the magnitude and quality of the lost habitat.
Identification of Human Oral Keratinocyte Stem/Progenitor Cells by Neurotrophin Receptor p75 and the Role of Neurotrophin/p75 Signaling
Authors: Nakamura Takahiro , Endo Ken-ichi , Kinoshita Shigeru
Published: November 2006

This study was undertaken to determine whether human oral keratinocyte stem cells characteristically express higher levels of the low-affinity neurotrophin receptor p75 and to elucidate the function of p75 in oral keratinocytes. Examination of their expression patterns and cell-cycling status in vivo showed that p75 was exclusively expressed in the basal cell layer of both the tips of the papillae and the deep rete ridges. These immunostaining patterns suggest a cluster organization; most p75(+) cells did not actively cycle in vivo. Cell sorting showed that cells in the p75(+) subset were smaller and possessed higher in vitro proliferative capacity and clonal growth potential than the p75(−) subset. Clonal analysis revealed that holoclone-type (stem cell compartment), meroclone-type (intermediate compartment), and paraclone-type (transient amplifying cell compartment) cells, previously identified in skin and the ocular surface, were present in human oral mucosal epithelium. Holoclone-type cells showed stronger p75 expression at both the mRNA and protein level than did meroclone- and paraclone-type cells. Among the several neurotrophins, nerve growth factor (NGF) and neurotrophin-3 stimulated p75(+) oral keratinocyte cell proliferation, and only NGF protected them from apoptosis. Our in vivo and in vitro findings indicate that p75 is a potential marker of oral keratinocyte stem/progenitor cells and that some neurotrophin/p75 signaling affects cell growth and survival.
Human Mesenchymal Stromal Cells Regulate Initial Self-Renewing Divisions of Hematopoietic Progenitor Cells by a β1-Integrin-Dependent Mechanism
Authors: Gottschling Sandra , Saffrich Rainer , Seckinger Anja , Krause Ulf , Horsch Kerstin , Miesala Katrin , Ho Anthony D.
Published: November 2006

In previous reports, we have demonstrated that only direct cell-cell contact with stromal cells, such as the murine stromal cell line AFT024, was able to alter the cell division kinetics and self-renewing capacity of hematopoietic progenitor cells (HPC). Because β1-integrins were shown to be crucial for the interaction of HPC with the bone marrow microenvironment, we have studied the role of β1-integrins in the regulation of self-renewing cell divisions. For this purpose, we used primary human mesenchymal stromal (MS) cells as in vitro surrogate niche and monitored the division history and subsequent functional fate of individually plated CD34+133+ cells in the absence or presence of an anti-β1-integrin blocking antibody by time-lapse microscopy and subsequent long-term culture-initiating cell (LTC-IC) assays. β1-Integrin-mediated contact with MS cells significantly increased the proportion of asymmetrically dividing cells and led to a substantial increase of LTC-IC. Provided that β1-integrin-mediated contact was available within the first 72 hours, human MS cells were able to recruit HPC into cell cycle and accelerate their division kinetics without loss of stem cell function. Activation of β1-integrins by ligands alone (e.g., fibronectin and vascular cell adhesion molecule-1) was not sufficient to alter the cell division symmetry and promote self-renewal of HPC, thus indicating an indirect effect. These results have provided evidence that primary human MS cells are able to induce self-renewing divisions of HPC by a β1-integrin-dependent mechanism.
Erythropoietin Receptor Expression in Non-Small Cell Lung Carcinoma: A Question of Antibody Specificity
Authors: Brown W. Mark , Maxwell Perry , Graham Alastair N.J. , Yakkundi Anita , Dunlop Elaine A. , Shi Zhanzhong , Johnston Patrick G. , Lappin Terence R.J.
Published: November 2006

Immunohistochemical studies on formalin-fixed, paraffin-embedded (FFPE) tissue utilizing polyclonal antibodies form the cornerstone of many reports claiming to demonstrate erythropoietin receptor (EPOR) expression in malignant tissue. Recently, Elliott et al. (Blood 2006;107:1892–1895) reported that the antibodies commonly used to detect EPOR expression also detect non-EPOR proteins, and that their binding to EPOR was severely abrogated by two synthetic peptides based on the sequence of heat shock protein (HSP) 70, HSP70-2, and HSP70-5. We have investigated the specificity of the C20 antibody for detecting EPOR expression in non-small cell lung carcinoma (NSCLC) utilizing tissue microarrays. A total of 34 cases were available for study. Antibody absorbed with peptide resulted in marked suppression of cytoplasmic staining compared with nonabsorbed antibody. Four tumors that initially showed a membranous pattern of staining retained this pattern with absorbed antibody. Positive membranous immunoreactivity was also observed in 6 of 30 tumors that originally showed a predominantly cytoplasmic pattern of staining. Using the C20 antibody for Western blots, we detected three main bands, at 100, 66, and 59 kDa. Preincubation with either peptide caused abolition of the 66-kDa band, which contains non-EPOR sequences including heat shock peptides. These results call into question the significance of previous immunohistochemical studies of EPOR expression in malignancy and emphasize the need for more specific anti-EPOR antibodies to define the true extent of EPOR expression in neoplastic tissue.
Climatic control on river discharge simulations, Mittivakkat Glacier catchment, Ammassalik Island, SE Greenland*
Authors: Mernild S.H. , Hasholt B.
Published: November 2006

A lumped conceptual Rainfall–Runoff Model (the NAM model) was applied to quantify simulated intra- and inter-annual discharge from the Mittivakkat glacier catchment (18.4 km2, 78% glacier cover), Ammassalik Island, SE Greenland. Discharge simulations were performed for three periods: 1999–2004 (calibration period), 1993–1995 and 1998/1999 (validation period), and 2071–2100 (scenario period). In periods when observed winter discharges were lacking, visual observations from daily photographic time lapse were used for calibration. The timing and magnitude of simulated discharge were in general in good accordance with observed discharge (R2=0.77). However, discrepancies between simulated and observed discharge occur (maximum daily difference up to 3.4 m3 s−1, up to 11% difference between observed and simulated cumulative discharge, and model predicted river break-up 1–3 d before it actually occurs). For the period 2071–2100 future IPCC A2 and IPCC B2 climate scenarios were used as input for NAM based on HIRHAM RCM and HadCM3 AOGCM model simulations. The IPCC scenarios indicated mean maximum monthly runoff higher than 900 mm w.eq., and mean annual runoff around 3200 mm w.eq. yr−1, approximately one and a half times higher than the runoff in 1993–2004 of approximately 2000 mm w.eq. yr−1. The increasing runoff indicated an approximately three times higher negative glacier net mass balance ranging from about −750 mm w.eq. yr−1 (1961–1990) to approximately −2000 mm w.eq. yr−1 (2071–2100).
Long-term changes in lake ice cover in Finland*
Authors: Korhonen Johanna
Published: November 2006

The freeze-up and break-up records of almost ninety lakes, and ice thickness of about thirty lakes, were analysed in order to identify long-term changes in the ice regime in Finland. The longest time series of break-up and freeze-up of ice in lakes are available from the early 19th century, while the earliest ice thickness measurements started in the 1910s. The analysis showed that there is a significant change towards earlier ice break-up in Finland except in the very north from the late 19th century to the present time. There is also a significant trend towards later freeze-up and thus also towards a shorter ice cover duration for the longest time series. However, for most lakes, for which data are not available prior to 1900, there are no significant trends. The ice thickness seems to have increased over the last 40 years, although there are significant trends only in half of the investigated lakes and significant decrease in the maximum ice thickness was found in four lakes in southern Finland. The increased ice thickness is most likely due to heavy snow on the ice and production of snow ice.
Trend analysis of Icelandic discharge, precipitation and temperature series
Authors: Jónsdóttir Jóna Finndís , Jónsson Páll , Uvo Cintia B.
Published: November 2006

This study is a part of a Nordic co-operative research project, Climate and Energy, funded by Nordic Energy Research and the Nordic energy sector. The project has the objective of a comprehensive assessment of the impact of climate change on Nordic renewable energy resources including hydropower, wind power, biofuels and solar energy. In this paper, the long term variability of precipitation, temperature and discharge of Icelandic rivers is analyzed with respect to trends. Trend is tested for two periods: 1941–2002, since the longest Icelandic discharge records reach 60 years back in time, and 1961–2000, so that a larger set of discharge records could be included, as only a few Icelandic discharge records extend more than 40 years back in time. An eventual trend in the time series is analyzed using the Mann–Kendall test. The test is applied to the time series of both annual and seasonal values, and also to the timing and volume of the maximum daily discharge in spring and autumn, respectively. The main conclusions from the study are that, despite significant increase in measured precipitation, discharge in non-glacial rivers has not increased. Meanwhile, spring temperatures have a negative trend and spring floods, therefore, are larger and delayed.
Assessment of precipitation and snowcover in northern research basins*
Authors: Young Kathy L. , Robert Bolton W. , Killingtveit Ånund , Yang Daqing
Published: November 2006

In 2004, a workshop was held to collect and synthesize the water balance data from 39 northern research basins (NRB) in Victoria, BC, Canada. One of the recommendations from the meeting was a need to review systematically each component of the water balance for these northern basins in order to identify spatial and temporal trends and to address significant knowledge gaps. Here, we assess the methodologies for measuring snow and rain in these northern basins; examine the temporal and spatial patterns of snow accumulation both during and at the end-of-the winter; consider ablation patterns and comment on the occurrence of extreme events. Our evaluation indicates that northern hydrologists still employ a variety of gauges and approaches to both measure and correct precipitation. For the NRB, rainfall contributions dominate in lower latitudes while snowfall gains importance with higher latitudes and altitude. Occurrence of large water bodies, topography (i.e. aspect, slope) and vegetation influence precipitation amount and its distribution across the landscape. Only two NRB studies showed a declining trend in snowcover (SWE). Snow is still considered the most important input of water in these northern basins, but extreme summer precipitation events (both rain and snow) have triggered higher magnitude floods than seasonal snowmelt runoff. Glacierized basins are sensitive to summer snowfalls and low winter snow storage. Both have the potential to dampen or enhance melting despite warmer or cooler air temperatures. Standardized gauges, approaches and continued monitoring of the NRB is encouraged.
Method for correction of annual precipitation records using the water balance approach*
Authors: Salo Yuri A.
Published: November 2006

Precipitation gauge measurements suffer from several sources of errors which can strongly influence their accuracy. The method proposed in the paper is based on the correction of annual precipitation records for a given river basin using the water balance equation. The main advantage of the approach is in using the annual runoff records and air temperature data, which are measured more accurately than the annual precipitation amount. Two versions of the computation scheme (for a multi-year period and for an annual interval) are presented and discussed. The water balance equation taken into account in this study combines the area averaged annual measured precipitation, runoff, evapotransporation and, over an annual time scale, the change in moisture in surface and undersurface storages. The Ol'decop formula for calculation of evapotranspiration together with the improved regional formula for potential evaporation as a function of annual air temperature is used in this study. It has been determined for the annual time interval that the storage of water in a basin is strongly dependent on annual air temperature and, to a lesser extent, on precipitation. An example of the method application for two catchments situated in Northwest Russia is presented, too.
An investigation of cadmium and lead from a High Arctic waste disposal site, Rsesolute Bay, Nunavut, Canada*
Authors: Young Kathy L. , Lund Karen
Published: November 2006

Heavy metal contamination in the High Arctic is a growing concern. Cadmium and lead are recognized by the Canadian Government as metals of concern but little research has been done on small point sources such as municipal waste disposal sites. In 2003 a study was conducted near Resolute, Nunavut, Canada (74°43′N, 95°55′W) to determine the extent of cadmium and lead leaching from a local dumpsite which lay adjacent to a large late-lying snowbed. Three transects (reaching ∼700 m in length) were established downslope from the waste site and water and soil samples were collected for metal analysis at regular intervals. Information on snowbed retreat, water table position, soil moisture conditions and frost table decline were also obtained. Cadmium levels in water samples exceeded government guidelines and along one transect increased with distance. Little lead in surface waters supports the notion that it does not travel easily in soil solution. Overall, soil cadmium and lead levels were low and did not exceed government guidelines. Some spatial patterns did emerge and can be linked to variations in water flow patterns, nearness to the dumpsite and ground cover conditions.
Dementia and Occupation: A Review of the Literature
Authors: Egan Mary , Hobson Sandra , Fearing Virginia G.
Published: November 2006

Background. Recent evidence supports the usefulness of occupational therapy models, particularly the Occupational Performance Process, in structuring research evidence to inform practice. Purpose. In this paper we report the results of our work to identify and summarize quantitative and qualitative research evidence about occupational therapy intervention for individuals with Alzheimer's disease and their caregiver, relevant to the first stage of the Occupational Performance Process, which is to identify, validate and prioritize occupational performance issues. Results. Review of literature from diverse sources deemed to be relevant was summarized under three themes: the experience of occupation among persons with dementia, the experience of occupation among caregivers of persons with dementia, and discussion of occupational performance issues. Practice Implications. Best practice recommendations are made based on this review.
The Role of 17 α-Hydroxyprogesterone Caproate in the Prevention of Preterm Birth
Authors: Meis Paul J
Published: November 2006

Preterm birth is a major public-health problem in the USA, which has higher rates of preterm birth than most other developed countries. Attempts at the prevention of preterm birth have been largely unsuccessful. The recent publication of a large, multicenter, randomized trial of 17 α-hydroxyprogesterone caproate, which showed efficacy in preventing recurrent preterm delivery, has sparked renewed interest in progestational drugs in general and this compound in particular for use in preventing preterm delivery. Although this drug is not currently commercially available, an application has been made to the US FDA to produce 17 α-hydroxyprogesterone caproate, as Gestiva™ for the prevention of preterm delivery.
The Metabolic Syndrome in Women
Authors: Rosano Giuseppe MC , Vitale Cristiana , Mercuro Giuseppe
Published: November 2006

The clustering of metabolic risk factors, overweight and hypertension is of particular importance in postmenopausal women due to the negative effect of menopause on bodyweight, glucose metabolism and the development of hypertension. Menopause acts directly as a risk factor by reducing the direct beneficial effect of ovarian hormones on cardiovascular functions, and indirectly by negatively influencing traditional risk factors for coronary artery disease. All changes occurring after the menopause must be regarded under a unifying mechanism that induces unfavorable changes in cardiovascular risk factors and vascular functions, which interact with each other, amplifying the effect of ovarian hormone deficiency and aging.
DFT and neutron diffraction study of 1,6-anhydro-β-D-glucopyranose (levoglucosan)
Authors: Sládkovic̆ová Mariana , Mach Pavel , Smrc̆ok L’ubomír , Rundlöf Håkan
Published: November 2006

Geometries of 27 generated conformers of levoglucosan were optimized in vacuo at DFT level of theory combining several functionals with high quality basis sets. For the sake of comparison a reference molecular and crystal geometry obtained from 30 K single crystal neutron diffraction data was used. Analysis of the conformers’ geometries revealed that in all stable conformers intramolecular two-or three centre hydrogen bonds were formed. Relative energy of the conformer, which approximated the molecule in the crystal structure the most, was only ∼3 kcal/mol higher, than the energy of the most stable conformer in vacuo. The largest discrepancies between the geometries calculated in vacuo and experimental geometry concentrated in the vicinity of anomeric C1. These differences were reduced by involving O1 to intermolecular hydrogen bond using a simple model of the respective hydrogen bond in the crystal.
Thermodynamics
Authors: Sandler Stanley I.
Published: November 2006

Thermodynamics is a discipline with broad applications based on three basic principles: Conservation of mass, conservation of energy (first law), and isolated systems evolve toward an equilibrium, time‐invariant state in which temperature and pressure are spatially uniform, and in composition is uniform in each phase (ie, vapor, liquid, or solid). It is shown here how these principles lead to a broad range of applications. These include the analysis of heat engines, heat pumps (refrigerators), turbines, fuel cells, and understanding and predicting phase transitions among the solid, liquid, and vapor phases in both pure fluids and mixtures and chemical equilibria.
Toxicology
Authors: Britt Janice K. , James Robert C.
Published: November 2006

Toxicology is the study of interactions between chemicals and biological systems. Toxicology attempts to identify the adverse effects chemicals might induce in humans and the dose‐response relationships that would allow one to predict the relative safety/risk of a chemical exposure. Toxicological investigations attempt to define the nature of the harmful effect; severity of the effect as a function of exposure or dose; mechanism(s) causing the effects; detection, recognition, and quantitation of toxic effects; and reversibility of adverse effects. Toxic effects may be classified as local or systemic; and as latent, persistent, cumulative, or transient. They can include inflammation, necrosis, immunosuppression, neoplasia, mutagenesis, neurotoxicity, enzyme inhibition, teratogenesis, as well as others. Factors influencing toxicity include number, magnitude, and routes of exposures; and time of dosing, as well as formulation and impurities of materials. Routes of exposure include ingestion, through the skin (dermal), and inhalation, or multiple routes may be involved. The site of absorption, the metabolism of the toxic agent in organs like the liver and kidney, and the distribution of the agent and its metabolites to different tissues are all toxicokinetic features that may impact the toxicity of the chemical. Dose‐response relationships are useful in determining causality, range of sensitivity in a population and hence of hazard, assessment of no‐ or minimum‐effects doses. Dose‐response comparisons across species are helpful in predicting the possible range of human sensitivity when human data are unavailable. Dose–response comparisons across chemicals are useful for defining potency differences that may be used to select the best chemical available for a specific application. Toxicology testing procedures may be general or specific, and many guidelines must be followed. General studies monitor body weight, hematology, chemical pathology, and organ weight, among others; and types of studies include acute toxicity studies, short‐term repeated studies, and chronic and subchronic toxicity studies. Examples of specific studies include primary irritancy and immune‐mediated hypersensitivity studies, and neurological and behavioral toxicology. Review of studies and the relevance of toxicology in hazard evaluation are briefly examined. An introduction to the risk assessment process and its use of toxicity data is provided.