Molecular evolution of dentin phosphoprotein among toothed and toothless animals

<p>Abstract</p> <p>Background</p> <p>Dentin sialophosphoprotein (DSPP) is the largest member of the SIBLING family and is the most abundant noncollagenous protein in dentin. DSPP is also expressed in non-mineralized tissues including metabolically active ductal epithelia and some cancers. Its function, however, is poorly defined. The carboxy-terminal fragment, dentin phosphoprotein (DPP) is encoded predominantly by a large repetitive domain that requires separate cloning/sequencing reactions and is, therefore, often incomplete in genomic databases. Comparison of DPP sequences from at least one member of each major branch in the mammalian evolutionary tree (including some "toothless" mammals) as well as one reptile and bird may help delineate its possible functions in both dentin and ductal epithelia.</p> <p>Results</p> <p>The BMP1-cleavage and translation-termination domains were sufficiently conserved to permit amplification/cloning/sequencing of most species' DPP. While the integrin-binding domain, RGD, was present in about half of species, only vestigial remnants of this tripeptide were identified in the others. The number of tandem repeats of the nominal SerSerAsp phosphorylation motif in toothed mammals (including baleen whale and platypus which lack teeth as adults), ranged from ~75 (elephant) to >230 (human). These repeats were not perfect, however, and patterns of intervening sequences highlight the rapidity of changes among even closely related species. Two toothless anteater species have evolved different sets of nonsense mutations shortly after their BMP1 motifs suggesting that while cleavage may be important for DSPP processing in other tissues, the DPP domain itself may be required only in dentin. The lizard <it>DSPP </it>had an intact BMP1 site, a remnant RGD motif, as well as a distinctly different Ser/Asp-rich domain compared to mammals.</p> <p>Conclusions</p> <p>The DPP domain of <it>DSPP </it>was found to change dramatically within mammals and was lost in two truly toothless animals. The defining aspect of DPP, the long repeating phosphorylation domain, apparently undergoes frequent slip replication and recombination events that rapidly change specific patterns but not its overall biochemical character in toothed animals. Species may have to co-evolve protein processing mechanisms, however, to handle increased lengths of DSP repeats. While the RGD domain is lost in many species, some evolutionary pressure to maintain integrin binding can be observed.</p

Teaching Employment Skills to Carla within Inclusive Postsecondary Education

The purpose of this intervention-based case study is to provide an overview of an intervention aimed at improving employment skills for Carla, a 22-year-old female with intellectual disability enrolled in an inclusive postsecondary education program (IPSE). One specific aim of the IPSE is to prepare graduates for competitive integrated employment and inclusive community opportunities. Data has consistently indicated that individuals with intellectual and developmental disabilities (IDD) experience poorer employment outcomes compared to their peers without disabilities (Lipscomb et al., 2017) and one barrier to employment for individuals with IDD include lack of soft skills. One intervention that has been developed to address improving soft-skills is UPGRADE Your Performance and includes multiple components (i.e., goal setting, self-evaluation, self-graphing, self-monitoring, & technology-aided instruction). A recent study was conducted with Carla and other young adults attending the same IPSE and who were working competitively in the community. This case study highlights the specific experience of one of the participants, Carla. This case study describes her unique needs, how modifications were identified to increase Carla’s response to the intervention, and what additional supports were provided to improve her progress towards her employment goals. Implications for future research and recommendation for current and future teachers are provided. In addition, questions have been posed for potential use in teacher preparation programs

Managing Forest Conflicts: Perspectives of Indonesia's Forest Management Unit Directors

Recent expansion of the forestry and plantation sectors in Indonesia has intensified agrarian and natural resource conflicts, and created increased awareness of the social, economic and environmental impacts of these disputes. Addressing these disputes is a critical issue in advancing Indonesia's commitment to sustainable forest management. The Forest Management Units (Kesatuan Pengelolaan Hutan, or KPH), have become the pivotal structural element for managing all state forests at the local level, with responsibility for conventional forest management and policy implementation (establishing management boundaries, conducting forest inventory, and developing forest management plans), as well as the legal mandate to communicate and work with indigenous people and local communities. This paper presents the results of a national survey of all currently functioning KPH units, the first of its kind ever conducted with KPH leadership, to obtain a system-wide perspective of the KPHs' role, mandate, and capacity for serving as effective intermediaries in managing forest conflicts in Indonesia. The survey results show that the KPHs are still in a very initial stage of development, and are struggling with a complex and rapidly evolving policy and institutional framework. The most common conflicts noted by respondents included forest encroachment, tenure disputes, boundary conflicts, and illegal logging and land clearing. KPH leadership views conflict resolution as among their primary duties and functions, and underscored the importance of more proactive and collaborative approaches for addressing conflict, many seeing themselves as capable facilitators and mediators. Overall, these results juxtapose a generally constructive view by KPH leadership over their role and responsibility in addressing forest management conflicts, with an extremely challenging social, institutional, and political setting. The KPHs can certainly play an important role as local intermediaries, and in some cases, as facilitative mediators in resolving local conflicts, but only with a more concerted effort from central and provincial government authorities to provide greater consistency in policies and regulations, improved policy communication, and a sustained commitment to strengthening the capacity of individual KPHs

Managing Forest Conflicts: Perspectives of Indonesia’s Forest Management Unit Directors

Recent expansion of the forestry and plantation sectors in Indonesia has intensified agrarian and natural resource conflicts, and created increased awareness of the social, economic and environmental impacts of these disputes. Addressing these disputes is a critical issue in advancing Indonesia’s commitment to sustainable forest management.  The Forest Management Units (Kesatuan Pengelolaan Hutan, or KPH), have become the pivotal structural element for managing all state forests at the local level, with responsibility for conventional forest management and policy implementation (establishing management boundaries, conducting forest inventory, and developing forest management plans), as well as the legal mandate to communicate and work with indigenous people and local communities.  This paper presents the results of a national survey of all currently functioning KPH units, the first of its kind ever conducted with KPH leadership, to obtain a system-wide perspective of the KPHs’ role, mandate, and capacity for serving as effective intermediaries in managing forest conflicts in Indonesia. The survey results show that the KPHs are still in a very initial stage of development, and are struggling with a complex and rapidly evolving policy and institutional framework. The most common conflicts noted by respondents included forest encroachment, tenure disputes, boundary conflicts, and illegal logging and land clearing.  KPH leadership views conflict resolution as among their primary duties and functions, and underscored the importance of more proactive and collaborative approaches for addressing conflict, many seeing themselves as capable facilitators and mediators. Overall, these results juxtapose a generally constructive view by KPH leadership over their role and responsibility in addressing forest management conflicts, with an extremely challenging social, institutional, and political setting. The KPHs can certainly play an important role as local intermediaries, and in some cases, as facilitative mediators in resolving local conflicts, but only with a more concerted effort from central and provincial government authorities to provide greater consistency in policies and regulations, improved policy communication, and a sustained commitment to strengthening the capacity of individual KPHs.

One-Dimensional Lateral Force Anisotropy at the Atomic Scale in Sliding Single Molecules on a Surface

Using a q+ atomic force microscopy at low temperature, a sexiphenyl molecule is slid across an atomically flat Ag(111) surface along the direction parallel to its molecular axis and sideways to the axis. Despite identical contact area and underlying surface geometry, the lateral force required to move the molecule in the direction parallel to its molecular axis is found to be about half of that required to move it sideways. The origin of the lateral force anisotropy observed here is traced to the one-dimensional shape of the molecule, which is further confirmed by molecular dynamics simulations. We also demonstrate that scanning tunneling microscopy can be used to determine the comparative lateral force qualitatively. The observed one-dimensional lateral force anisotropy may have important implications in atomic scale frictional phenomena on materials surfaces

Dose-dense adjuvant chemotherapy for primary breast cancer

Adjuvant chemotherapy has been proven to reduce significantly the risk for relapse and death in women with operable breast cancer. Nevertheless, the prognosis for patients presenting with extensive axillary lymph node involvement remains suboptimal. In an attempt to improve on the efficacy of existing chemotherapy, a phase III intergroup trial led by the Cancer and Leukemia Group B (CALGB 97-41) was designed, which tested a mathematical model of tumor growth based on the Norton–Simon hypothesis. This hypothesis, developed about 3 decades ago, and the kinetic model derived from it, created the basis of the concepts of dose density and sequential therapy, both of which were tested in CALGB 97-41. This large prospective randomized trial demonstrated that shortening the time interval between each chemotherapy cycle while maintaining the same dose size resulted in significant improvements in disease-free and overall survival in patients with node-positive breast carcinoma. This finding is highly relevant and has immediate implications for clinical practice

A comprehensive analysis of normal variation and disease-causing mutations in the human DSPP gene

Within nine dentin dysplasia (type II) and dentinogenesis imperfecta (type II and III) patient/families, seven have one of four net −1 deletions within the ~2kb coding repeat domain of the DSPP gene while the remaining two patients had splice-site mutations. All frameshift mutations are predicted to change the highly soluble DSPP protein into proteins with long hydrophobic amino acid repeats that could interfere with processing of normal DSPP and/or other secreted matrix proteins. We propose that all previously reported missense, nonsense, and splice-site DSPP mutations (all associated with exons 2 and 3) result in dominant phenotypes due to disruption of signal peptide-processing and/or related biochemical events that also result in interference with protein processing. This would bring the currently known dominant forms of the human disease phenotype in agreement with the normal phenotype of the heterozygous null Dspp (−/+) mice. A study of 188 normal human chromosomes revealed a hypervariable DSPP repeat domain with extraordinary rates of change including 20 slip-replication indel events and 37 predominantly C-to-T transition SNPs. The most frequent transition in the primordial 9-bp DNA repeat was a sense-strand CpG site while a CpNpG (CAG) transition was the second most frequent SNP. Bisulfite-sequencing of genomic DNA showed that DSPP repeat can be methylated at both motifs. This suggests that, like plants and some animals, human methylate some CpNpG sequences. Analysis of 37 haplotypes of the highly variable DSPP gene from geographically diverse people suggests it may be a useful autosomal marker in human migration studies

Population Density and Phenology of Tetranychus urticae (Acari: Tetranychidae) in Hop is Linked to the Timing of Sulfur Applications

The twospotted spider mite, Tetranychus urticae Koch, is a worldwide pest of numerous agronomic and horticultural plants. Sulfur fungicides are known to induce outbreaks of this pest on several crops, although mechanisms associated with sulfur-induced mite outbreaks are largely unknown. Studies were conducted during 2007–2009 in Oregon and Washington hop yards to evaluate the effect of timing of sulfur applications on T. urticae and key predators. In both regions, applications of sulfur made relatively late in the growing season (mid-June to mid-July) were associated with the greatest exacerbation of spider mite outbreaks, particularly in the upper canopy of the crop. The severity of mite outbreaks was closely associated with sulfur applications made during a relatively narrow time period coincident with the early exponential phase of spider mite increase and rapid host growth. A nonlinear model relating mean cumulative mite days during the time of sulfur sprays to the percent increase in total cumulative mite days (standardized to a nontreated plot) explained 58% of the variability observed in increased spider mite severity related to sulfur spray timing. Spatial patterns of spider mites in the Oregon plots indicated similar dispersal of motile stages of spider mites among leaves treated with sulfur versus nontreated leaves; however, in two of three years, eggs were less aggregated on leaves of sulfur-treated plants, pointing to enhanced dispersal. Apart from one experiment in Washington, relatively few predatory mites were observed during the course of these studies, and sulfur-induced mite outbreaks generally occurred irrespective of predatory mite abundance. Collectively, these studies indicate sulfur induces mite outbreaks through direct or indirect effects on T. urticae, mostly independent of predatory mite abundance or toxicity to these predators. Avoidance of exacerbation of spider mite outbreaks by sulfur sprays was achieved by carefully timing applications to periods of low spider mite abundance and slower host development, which is generally early to mid-spring for hop.Keywords: pest resurgence, Humulus lupulus, Podosphaera macularis, conservation biological controlKeywords: pest resurgence, Humulus lupulus, Podosphaera macularis, conservation biological contro

Science and Ideology in Economic, Political, and Social Thought

This paper has two sources: One is my own research in three broad areas: business cycles, economic measurement and social choice. In all of these fields I attempted to apply the basic precepts of the scientific method as it is understood in the natural sciences. I found that my effort at using natural science methods in economics was met with little understanding and often considerable hostility. I found economics to be driven less by common sense and empirical evidence, then by various ideologies that exhibited either a political or a methodological bias, or both. This brings me to the second source: Several books have appeared recently that describe in historical terms the ideological forces that have shaped either the direct areas in which I worked, or a broader background. These books taught me that the ideological forces in the social sciences are even stronger than I imagined on the basis of my own experiences. The scientific method is the antipode to ideology. I feel that the scientific work that I have done on specific, long standing and fundamental problems in economics and political science have given me additional insights into the destructive role of ideology beyond the history of thought orientation of the works I will be discussing