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Search Results: 1 - 10 of 158164 matches for " Steven H Hinrichs "
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RAIphy: Phylogenetic classification of metagenomics samples using iterative refinement of relative abundance index profiles
Ozkan U Nalbantoglu, Samuel F Way, Steven H Hinrichs, Khalid Sayood
BMC Bioinformatics , 2011, DOI: 10.1186/1471-2105-12-41
Abstract: We propose a robust taxonomic classification method, RAIphy, that uses a novel sequence similarity metric with iterative refinement of taxonomic models and functions effectively without these limitations. We have tested RAIphy with synthetic metagenomics data ranging between 100 bp to 50 Kbp. Within a sequence read range of 100 bp-1000 bp, the sensitivity of RAIphy ranges between 38%-81% outperforming the currently popular composition-based methods for reads in this range. Comparison with computationally more intensive sequence similarity methods shows that RAIphy performs competitively while being significantly faster. The sensitivity-specificity characteristics for relatively longer contigs were compared with the PhyloPythia and TACOA algorithms. RAIphy performs better than these algorithms at varying clade-levels. For an acid mine drainage (AMD) metagenome, RAIphy was able to taxonomically bin the sequence read set more accurately than the currently available methods, Phymm and MEGAN, and more accurately in two out of three tests than the much more computationally intensive method, PhymmBL.With the introduction of the relative abundance index metric and an iterative classification method, we propose a taxonomic classification algorithm that performs competitively for a large range of DNA contig lengths assembled from metagenome data. Because of its speed, simplicity, and accuracy RAIphy can be successfully used in the binning process for a broad range of metagenomic data obtained from environmental samples.A principal goal of metagenomics [1] is to sample microbiomes and recover genetic material without isolating single organisms, thereby mitigating the problem of limiting genomic analysis to a small percentage of existing culturable species. Eventually, this will help extend the tree of life [2], enrich sequence libraries, and expand analysis from genomic to metagenomic (e.g., samples from various habitats could be used to study interactions within communities,
Genetic analysis of the Staphylococcus epidermidis Macromolecular Synthesis Operon: Serp1129 is an ATP binding protein and sigA transcription is regulated by both σA- and σB-dependent promoters
Kendall A Bryant, Lauren C Kinkead, Marilynn A Larson, Steven H Hinrichs, Paul D Fey
BMC Microbiology , 2010, DOI: 10.1186/1471-2180-10-8
Abstract: The ORFs of S. epidermidis were compared to the previously described MMSO of B. subtilis and two additional ORFs in S. epidermidis, serp1129 and serp1130, were identified. The largest transcript, 4.8 kb in length, was expressed only in exponential growth and encompassed all four ORFs (serp1130, serp1129, dnaG, and sigA). A separate transcript (1.5 kb) comprising serp1130 and serp1129 was expressed in early exponential growth. Two smaller transcripts 1.3 and 1.2 kb in size were detected with a sigA probe in both exponential and post-exponential phases of growth. Western blot analysis correlated with the transcriptional profile and demonstrated that Serp1129 was detected only in the exponential phase of growth. Computational analysis identified that Serp1130 contained a CBS motif whereas Serp1129 contained an ATP/GTP binding motif. Functional studies of Serp1129 demonstrated that it was capable of binding both ATP and GTP. Comparisons with a sigB:dhfr mutant revealed that the 1.3 kb sigA transcript was regulated by a σB-dependent promoter.These studies demonstrated that the S. epidermidis 1457 MMSO contains two ORFs (serp1129 and serp1130) not described within the B. subtilis MMSO and at least three promoters, one of which is σβ-dependent. The transcriptional regulation of sigA by σB provides evidence that the staphylococcal σB-dependent response is controlled at both the transcriptional and post-transcriptional level. The conservation of serp1129 across multiple gram-positive organisms and its capability to bind ATP and GTP support the need for further investigation of its role in bacterial growth.Replication of the bacterial chromosome is a complex process requiring the interaction of a variety of essential enzymes including primase, helicase, and DNA polymerases I and III [1]. It is hypothesized that bacteria co-regulate the expression of these unlinked genes to ensure the necessary proteins are available during chromosomal replication. To better understand these p
Large Direct Repeats Flank Genomic Rearrangements between a New Clinical Isolate of Francisella tularensis subsp. tularensis A1 and Schu S4
Ufuk Nalbantoglu,Khalid Sayood,Michael P. Dempsey,Peter C. Iwen,Stephen C. Francesconi,Ravi D. Barabote,Gary Xie,Thomas S. Brettin,Steven H. Hinrichs,Paul D. Fey
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0009007
Abstract: Francisella tularensis subspecies tularensis consists of two separate populations A1 and A2. This report describes the complete genome sequence of NE061598, an F. tularensis subspecies tularensis A1 isolated in 1998 from a human with clinical disease in Nebraska, United States of America. The genome sequence was compared to Schu S4, an F. tularensis subspecies tularensis A1a strain originally isolated in Ohio in 1941. It was determined that there were 25 nucleotide polymorphisms (22 SNPs and 3 indels) between Schu S4 and NE061598; two of these polymorphisms were in potential virulence loci. Pulsed-field gel electrophoresis analysis demonstrated that NE061598 was an A1a genotype. Other differences included repeat sequences (n = 11 separate loci), four of which were contained in coding sequences, and an inversion and rearrangement probably mediated by insertion sequences and the previously identified direct repeats I, II, and III. Five new variable-number tandem repeats were identified; three of these five were unique in NE061598 compared to Schu S4. Importantly, there was no gene loss or gain identified between NE061598 and Schu S4. Interpretation of these data suggests there is significant sequence conservation and chromosomal synteny within the A1 population. Further studies are needed to determine the biological properties driving the selective pressure that maintains the chromosomal structure of this monomorphic pathogen.
Inhibition of phosphorylated c-Met in rhabdomyosarcoma cell lines by a small molecule inhibitor SU11274
Jinxuan Hou, Jixin Dong, Lijun Sun, Liying Geng, Jing Wang, Jialin Zheng, Yan Li, Julia Bridge, Steven H Hinrichs, Shi-Jian Ding
Journal of Translational Medicine , 2011, DOI: 10.1186/1479-5876-9-64
Abstract: The expression level of phosphorylated c-Met in RMS cell lines (RD, CW9019 and RH30) and tumor tissues was assessed by phospho-RTK array and immunohistochemistry, respectively. The inhibition effects of SU11274 on RMS cells were studied with regard to intracellular signaling, cell proliferation, cell cycle and cell migration.A high level of phosphorylated c-Met was detected in 2 alveolar RMS cell lines (CW9019 and RH30) and 14 out of 24 RMS tissue samples, whereas relatively low levels of phospho-c-Met were observed in the embryonic RMS cell line (RD). The small molecule SU11274 could significantly reduce the phosphorylation of c-Met, resulting in inhibition of cell proliferation, G1 phase arrest of cell cycle and blocking of cell migration in CW9019 and RH30 cell lines.These results might support the role of c-Met in the development and progression of RMS. Furthermore, the inhibitor of c-Met, SU11274, could be an effective targeting therapy reagent for RMS, especially alveolar RMS.Rhabdomyosarcoma (RMS) is the most common soft tissue tumor in childhood, accounting for up to 50% of all soft tissue sarcomas [1]. While in adults, RMS represents about 15-20% of all soft tissue sarcomas [2]. There are two main histologically distinct subtypes of RMS: embryonal RMS (ERMS) and alveolar RMS (ARMS) [3]. ERMS is composed of spindle-shaped cells with a stromal rich appearance and occurs mainly in the head and neck region. It is the most frequently diagnosed variant with a generally good prognosis and presents early with an onset around the age of 2-5 years [3,4]. In contrast, ARMS consists of small, round, densely packed cells and occurs more often in the trunk and extremities. ARMS is primarily diagnosed in adolescents and is associated with a poor prognosis as patients often present with metastatic disease [5]. Chemotherapy is the most common therapeutic option for RMS. The regimens are typically based on variations of the well-established vincristine, actinomycin D and cyc
Complete Genome Sequence of Francisella tularensis Subspecies holarctica FTNF002-00
Ravi D. Barabote, Gary Xie, Thomas S. Brettin, Steven H. Hinrichs, Paul D. Fey, Justin J. Jay, Jennifer L. Engle, Shubhada D. Godbole, Jyothi M. Noronha, Richard H. Scheuermann, Liwei W. Zhou, Christine Lion, Michael P. Dempsey
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0007041
Abstract: Francisella tularensis subspecies holarctica FTNF002-00 strain was originally obtained from the first known clinical case of bacteremic F. tularensis pneumonia in Southern Europe isolated from an immunocompetent individual. The FTNF002-00 complete genome contains the RD23 deletion and represents a type strain for a clonal population from the first epidemic tularemia outbreak in Spain between 1997–1998. Here, we present the complete sequence analysis of the FTNF002-00 genome. The complete genome sequence of FTNF002-00 revealed several large as well as small genomic differences with respect to two other published complete genome sequences of F. tularensis subsp. holarctica strains, LVS and OSU18. The FTNF002-00 genome shares >99.9% sequence similarity with LVS and OSU18, and is also ~5 MB smaller by comparison. The overall organization of the FTNF002-00 genome is remarkably identical to those of LVS and OSU18, except for a single 3.9 kb inversion in FTNF002-00. Twelve regions of difference ranging from 0.1–1.5 kb and forty-two small insertions and deletions were identified in a comparative analysis of FTNF002-00, LVS, and OSU18 genomes. Two small deletions appear to inactivate two genes in FTNF002-00 causing them to become pseudogenes; the intact genes encode a protein of unknown function and a drug:H+ antiporter. In addition, we identified ninety-nine proteins in FTNF002-00 containing amino acid mutations compared to LVS and OSU18. Several non-conserved amino acid replacements were identified, one of which occurs in the virulence-associated intracellular growth locus subunit D protein. Many of these changes in FTNF002-00 are likely the consequence of direct selection that increases the fitness of this subsp. holarctica clone within its endemic population. Our complete genome sequence analyses lay the foundation for experimental testing of these possibilities.
Molecular Approaches to Sarcoma Therapy
R. J. Olsen,S. R. Tarantolo,S. H. Hinrichs
Sarcoma , 2002, DOI: 10.1080/13577140220127530
Abstract: Soft tissue sarcomas comprise a heterogeneous group of aggressive tumors that have a relatively poor prognosis. Although conventional therapeutic regimens can effectively cytoreduce the overall tumor mass, they fail to consistently achieve a curative outcome. Alternative gene-based approaches that counteract the underlying neoplastic process by eliminating the clonal aberrations that potentiate malignant behavior have been proposed. As compared to the accumulation of gene alterations associated with epithelial carcinomas, sarcomas are frequently characterized by the unique presence of a single chromosomal translocation in each histological subtype. Similar to the Philadelphia chromosome associated with CML, these clonal abnormalities result in the fusion of two independent unrelated genes to generate a unique chimeric protein that displays aberrant activity believed to initiate cellular transformation. Secondary gene mutations may provide an additional growth advantage that further contributes to malignant progression. The recent clinical success of the tyrosine kinase inhibitor, STI571, suggests that therapeutic approaches specifically directed against essential survival factors in sarcoma cells may be effective. This review summarizes published approaches targeting a specific molecular mechanism associated with sarcomagenesis. The strategy and significance of published translational studies in six distinct areas are presented. These include: (1) the disruption of chimeric transcription factor activity; (2) inhibition of growth stimulatory post-translational modifications; (3) restoration of tumor suppressor function; (4) interference with angiogenesis; (5) induction of apoptotic pathways; and (6) introduction of toxic gene products. The potential for improving outcomes in sarcoma patients and the conceptual obstacles to be overcome are discussed.
Monitoring Endangered Species Populations: Gene Dispersal Can Have Pronounced Effects on the Relationship between Census Size and Genetic Diversity  [PDF]
Steven H. Rogstad, Stephan Pelikan
American Journal of Plant Sciences (AJPS) , 2013, DOI: 10.4236/ajps.2013.410238

Anthropogenic activities are increasing habitat fragmentation, as well as the number of threatened and endangered species. Thus, isolated fragments with natural remnant stands, or in situ or ex situ endangered species rescue populations, are on the rise. The most common method for assessing the “conservation health” of such populations is to determine or estimate the census size. However, while it is known that the census size of a population does not always correlate with its genetic diversity, methods for modeling how different factors can drive variation in the relationship of census size to genetic diversity in plant populations are needed. Here we use the computer program NEWGARDEN to investigate how the relationship of stand size versus genetic diversity (measured as both the percent of the founding alleles retained and FIT) can be extremely variable depending on founder number, founder density, and gene dispersal distances. Populations of endangered species that appear to have the same conservation health in terms of similar population numbers may differ greatly in their conservation health as indicated by the genetic diversity they retain. NEWGARDEN can be used to explore how different founding and intra- or interspecific life history characteristics can affect genetic diversity relative to census size. If proper historical data exist, NEWGARDEN can also be used to estimate the percent of founding genetic diversity remaining in a given stand.

Book Review: Managing Human Resource Development – an outcomes-based approach
Karen Hinrichs
South African Journal of Industrial Psychology , 2002, DOI: 10.4102/sajip.v28i2.44
Abstract: The range of contributing authors, including the editor, (who are certainly significantly representative of the HRD body of knowledge and application in this country) have chosen to address a longstanding gap in locally produced resources in this area. In that sense, the book is, indeed, long overdue (as pointed out in the foreword) and will make a meaningful contribution.
Book Review: South African Employment Relations – Theory and Practice
Karen Hinrichs
South African Journal of Industrial Psychology , 2004, DOI: 10.4102/sajip.v30i2.144
Abstract: South African Employment Relations – Theory and Practice Nel, P.S. (editor) (2002), Van Schaik Publishers This is the new edition of the previously published South African Industrial Relations and it specifically sets out to revisit this body of knowledge and update "theorists and practitioners" on developments in the field of labour or employment relations since 1999.
Das Eismeer – Caspar David Friedrich and the North
Nina Hinrichs
Nordlit : Tidsskrift i litteratur og kultur , 2008,
Abstract: The German Romantic painter Caspar David Friedrich (1774- 1840) created the work of art Das Eismeer in the years 1823/24. Besides his painting M nch am Meer it is his most radical painting. It depicts a dramatic and grim subject: A shipwreck in the Arctic Sea. According to different cultural, historical and social contexts there have been many different interpretations of his painting since it was produced.
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