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IMEG
SEMINARS
Spring 2004
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Previous
IMEG Seminars and Abstracts: |
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Date |
Speaker and title of seminar |
01/14/04 |
Speaker:
Dr. Arthur Lesk,
Dept. of Biochemistry and Molecular Biology, Penn State
University
Title: "Evolution of the globins."
Abstract: Globins have been subjects of studies of molecular evolution
because of the availability of sequence and structural data. Many
important principles have been developed in studies of this family.
Although the field was considered "cut-and-dried" recent
discoveries, of truncated globins that differ very substantially
from those known before, have reopened many questions about the
conserved and variable features of these molecules.
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01/21/04 |
Speaker:
Dr. Steven Schaeffer,
Dept. of Biology, Penn State University
Title: "Comparative Genomics of Drosophila: A repetitive element is found at
rearrangement breakpoints in D. pseudoobscura."
Abstract: Inversion mutations reshape Drosophila genomes by shuffling
the order of genes within chromosomes. Levels of inversion
diversity differ among chromosomal arms within and between species,
but the mechanism that generates these rearrangements is not widely
understood. Comparative analysis of the D. melanogaster and
D. pseudoobscura genomes rejects a random chromosomal
breakage model. An analysis of sequences in the neighborhood of
conserved linkage breaks identifies a novel conserved sequence motif
that is found at elevated frequency at intra- and interspecific
breakpoints in D. pseudoobscura and may serve as a hotspot
for genomic rearrangements. This talk will also provide an overview
of future Drosophila genome projects that are currently underway.
Reference:
Schaeffer,
S. W., P. Goetting-Minesky, M. Kovacevic, J. Peoples, J. L.
Graybill et al.,
2003. Evolutionary genomics of inversions in Drosophila
pseudoobscura: Evidence for epistasis. Proceedings of the
National Academy of Sciences
USA 100:8319-8324.
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01/28/04 |
Speaker:
Dr. Jim Marden, Dept.
of Biology, Penn State University
Title:
"Alternative splicing, muscle contraction
and intraspecific variation of dragonfly flight muscle."
Abstract: Flight muscles of Libellula pulchella dragonflies contain a
mixture of six alternatively spliced transcripts of a single
troponin T (TnT) gene. Intraspecific variation in the relative
abundance of different TnT transcripts affects the calcium
sensitivity of skinned muscle fibers and the performance of intact
muscles during work loop contraction regimes that approximate in
vivo conditions during flight. The relative abundance of one
TnT transcript, or the pooled relative abundance of two TnT
transcripts, shows a positive correlation with a ten-fold range of
variation in calcium sensitivity of skinned fibers (r2=0.77,
p<0.0001), and a three-fold range in peak specific force (r2=0.74,
p<0.0001), specific work per cycle (r2 = 0.54; p < 0.0001), and
maximum specific power output (r2=0.53, p= 0.0002) of intact muscle.
Muscle power output of individual male dragonflies is positively
related to their total fat content and to their mating success.
Thus, it appears that alternative splicing of TnT is regulated in a
manner that allows a finely tuned match between muscle energy
expenditure and energy supply. Individual males able to accumulate
more energy have more powerful muscle and higher fecundity.
Gregarine gut parasites interact with this system in some
interesting ways that we are now beginning to examine at the
molecular level. There is also interesting spatial variation in the
incidence of gut parasites that is associated with soil quality and
habitat productivity, which may affect prey abundance and the
ability of dragonflies to resist infection.
References:
Marden, J. H., G.H. Fitzhugh, M. Girgenrath, M. R. Wolf, and S.
Girgenrath, 2001. Alternative splicing, muscle contraction and
intraspecific variation: associations between troponin T
transcripts, calcium sensitivity, and the force and power output of
dragonfly flight muscles during oscillatory contraction. J. Exper.
Biol. 204:3457-3470.
Relates TnT transcripts to muscle contractility.
Marden, J.H., G.H. Fitzhugh, M.R. Wolf, K.D. Arnold, and B. Rowan,
1999. Alternative splicing, muscle calcium sensitivity, and the
modulation of dragonfly flight performance. PNAS 96:15304-15309.
Relates TnT transcripts to free flight wingbeat kinematics.
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02/04/04 |
Speaker:
Fabia Battistuzzi,
Dept. of Biology, Penn State University
Title:
"A genomic timescale of prokaryote evolution."
Abstract: The concept of molecular clocks has been applied to many different
groups of organisms but a timeline of the major divisions of the
prokaryotes is still lacking. Through the application of a
local-clock method to a concatenated set of genes we estimated a
timeline of the major groups of prokaryotes followed by an analysis
of their metabolisms. The role played by these metabolisms on the
geochemical conditions during the archean eon suggests that a
molecular evolutionary approach could be important not only to
outline the phylogenetic history of the prokaryotes but also as a
key to the early history of Earth. The analysis of the divergence
times of ecologically important groups has suggested, for example,
an early evolution of methanogenesis, as well as insights into the
evolutionary history of others metabolisms.
Reference:
A. Knoll, 2003.The geological consequences of evolution. Geobiology
1:3-14.
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02/11/04 |
Dr. Izabella
Makalowska, Dept. of Biology, Penn State University
Title: "Mammalian overlapping genes."
Abstract:
It is believed that 3.2 billion base pairs of the human genome
harbor about 35,000 protein-coding genes. On average one
could expect one gene per 300,000 nucleotides. Although, the
distribution of the genes in the human genome is not random,
it is rather surprising that a large number of genes overlap
in the mammalian genomes. Thousands of overlapping genes were
recently identified in the human and mouse genomes. However,
the origin and evolution of overlapping genes are still
unknown. We identified 1,316 pairs of overlapping genes in humans
and mice and studied their evolutionary patterns. It appears
that these genes do not demonstrate greater than usual
conservation. Studies of the gene structure and overlap pattern
showed that only a small fraction of analyzed genes preserved
exactly the same pattern in both organisms.
References:
Veeramachaneni V, W. Makalowski, M. Galdzicki, R. Sood, and I. Makalowska, 2004. Mammalian overlapping genes - the comparative
perspective. Genome Research 14:280-286.
Lehner, B., G. Williams, R. D. Campbell, and C. M. Sanderson, 2002. Antisense transcripts in the human genome. Trends Genet
18:63-65.
Shendure, J. and G. M. Church, 2002. Computational discovery of
sense-antisense transcription in the human and mouse genomes. Genome
Biol 3: RESEARCH0044.
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02/18/04 |
Speaker:
Dr. Hong Ma, Dept. of
Biology, Penn State University
Title:
"Functional dissection of the Arabidopsis RAD51 gene family
encoding recombination and DNA repair enzymes."
Abstract:
DNA double-stranded breaks (DSBs) can form during DNA
replication and are induced by DNA damaging radiation and
chemicals, and must be repaired to allow cell cycle progression. A
major pathway for repairing DSBs relies on homologous
recombination. In fact, meiotic homologous recombination requires
the generation of DSBs by specific enzymes. In yeast,
members of the RAD51 family encode homologs of the E. coli recA
recombination protein, and are required for repair of DNA
damage by radiation and for meiotic recombination. In Drosophila
and mammalian and chicken cell culture, RAD51 homologs are
critical for DSBs repair caused by radiation or chemicals.
Furthermore, mouse knockout mutants of some RAD51 homologs
are embryonic lethal, whereas yeast and Drosophila mutants are
viable. As in yeast, RAD51 homologs are important for meiosis
in Drosophila, but their role in vertebrate animals is not known
due to the early lethality. Arabidopsis has putative orthologs for
at least four of mammalian RAD51 homologs. One of these was
known to be required for meiosis in Arabidopsis and yeast.
We have analyzed the function of the other three and found that each
is required for meiosis, but dispensable for mitotic growth.
We will discuss possible implications of these results on the
conservation and divergence of this gene family in the context of
DNA repair, meiosis, and cell cycle regulation.
References:
There are many papers on this topic. The following might serve
as a reference:
Trends Biochem Sci. 2001 Feb; 26:131-6.
The Rad51 and Dmc1 recombinases: a non-identical twin relationship.
Masson JY, West SC.
Imperial Cancer Research Fund, Clare Hall Laboratories, South
Mimms, EN6 3LD, Herts, UK.
A double-strand break in genomic DNA that remains unrepaired can
be lethal for a cell. Indeed, the integrity of the genome is
paramount for survival. It is therefore surprising that some
cells deliberately introduce double-strand breaks at certain
times during their life cycle. Why might they do this? What are the
benefits? How are these breaks repaired? The answers to these
questions lie in understanding the basis of meiotic
recombination, the process that leads to genetic variation.
This review summarizes the key roles played by the two
recombinases, Dmc1 and Rad51, in the faithful repair of DNA
breaks.
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02/25/04 |
WUN
Bioinformations Online Seminar Series
Location: 310
Rider II Time:
12:00 p.m. (Noon)
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03/03/04 |
Speaker:
Valer Gotea, Dept. of Biology, Penn State University
Title: "Transposable elements can be found in protein structures."
Abstract: The high content in repetitive elements of eukaryotic genomes has
intrigued many. Because little was known about their precise
function, they were included in the category of "junk" DNA, and
regarded as unnecessary components of our genomes, or even as
genomic parasites and selfish DNA. Lately, however, they are more
and more regarded as genomic treasures, as evidence of their coding
capacity and regulatory function started to emerge. Different
studies have shown that transposable elements fragments can be found
in many protein coding genes, but none has shown three dimensional
models of proteins containing such fragments, which should be a
definitive proof of the gene translation and protein existence.
Therefore, the question still remains: are transposable elements
really likely to contribute to the diversity of our proteome? By
searching the PDB database, we found evidence suggesting that some
transposable elements (LINEs and LTRs) can contribute to our
proteomes, while others (Alus) are rather "unsuitable" for this
purpose. Because of the small size of current PDB database (24,248
structures as of February 13, 2004), we only found a few cases of
proteins with incorporated transposable elements fragments, but the
growth of the database in the future should help us in better
understanding the impact of transposable elements on protein
diversity.
References:
Caras, I. W., M. A. Davitz, et al., 1987. Cloning of
decay-accelerating factor suggests novel use of splicing to generate
two proteins. Nature 325:545-549.
Brosius, J., 1991. Retroposons - seeds of evolution. Science
251:753.
Makalowski, W., 2000. Genomic scrap yard: how genomes utilize all
that junk. Gene 259:61-67.
Nekrutenko, A. and W. H. Li, 2001. Transposable elements are found
in a large number of human protein-coding genes. Trends Genet.
17:619-21.
Lorenc, A. and W. Makalowski, 2003. Transposable elements and
vertebrate protein diversity. Genetica 118:183-91.
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03/10/04 |
No Classes - SPRING
BREAK
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03/17/04 |
Speaker:
Dr. Andrzej Konopka,
BioLingua Research
Title:
"Systems
thinking in biology:
Pragmatic inference and other principles of integrative modelling."
Abstract: A concept of a system as something opposite to an arbitrary
collection of “parts” has been associated with most (if not all)
efforts humans devoted to an explanation of the phenomenon of life
for over two recent millennia. However a systematic research
programme that specifically aimed at methods of systems thinking is
known only since 1930s. This conversation is devoted to a review, a
survey and a critique of current general methods of data integration
from two different perspectives: 1) logical and 2) relational. As
far as logic is concerned a sound distinction needs to be made
between the phenomenon to be modelled, its model, and the
(biomedical) savant who actually does modelling. [This -so called-
epistemic cut is a challenging problem when the terms of modelling
and sensitivities of modelers are incompatible with each other in a
way that obscures the actual phenomenon to be studied.] As far as
relational principles of clear thinking are concerned one needs to
focus on methods that would allow describing objects and relations
between them in a interchangeable manner. On the other hand all
pragmatic aspects of clear thinking require a relation of order that
would enable principles of causality (everything has its cause)
and hierarchical organization (everything is either an ancestor or a
descendant of something else). About a third of this conversation
will be devoted to specific examples of computational data
integration that will illustrate strengths as well as misgivings of
general methods of pragmatic inference known to date.
Recommended Reading:
Bertalanffy, von L., 1933. Modern Theories of Development: an
Introduction to Theoretical Biology. Oxford: Oxford University
Press.
Bertalanffy, von L., 1969. General System
Theory: Foundations, Development, Applications. New York: George
Braziller.
Konopka, A. K., 2003. Systems biology: aspects
related to genomics. In: Cooper DN, ed. Nature Encyclopedia of the
Human Genome. Vol. 5. London: Nature Publishing Group Reference,
459-465.
Konopka, A. K., 2002. Grand metaphors of
biology in the genome era. Computers & Chemistry 26:397-401.
Konopka, A. K, J. C. Crabbe, 2003. Practical
aspects of practicing interdisciplinary science. Computational
Biology and Chemistry 27:163-164.
Konopka, A. K., 2002. This is Biology: The
science of the living world by Ernst Mayr (Book Review).
Computers & Chemistry 26:543-545.
Lewontin, R., 2000. The Triple Helix: Gene
Organism and Environment. Cambridge, MA: Harvard University Press.
Lewontin, R., 2001. It Ain't Necessarily So:
The Dream of the Human Genome and Other Illusions (2-nd edition).
New York: New York Review Books.
Lewontin, R. C., 1996. Evolution as
Engineering. In: Collado-Vides J, Smith, T., and Magasanik, B., ed.
Integrative Approaches to Molecular Biology. Cambridge, MA: The MIT
Press.
Mikulecky, D. C., 2001. Robert Rosen
(1934-1998): a snapshot of biology's Newton. Computers &
Chemistry 25:317-327.
Mikulecky, D. C., 2001. The emergence of
complexity: science coming of age or science growing old?
Computers & Chemistry 25:341-348.
Mikulecky, D. C., 2001. Network thermodynamics
and complexity: a transition to relational systems theory.
Computers & Chemistry 25:369-391.
Pagels, H. R., 1989. The Dreams of Reason : The
Computer and the Rise of the Sciences of Complexity. New York:
Bantam.
Pattee, H. H., 1969. How does a molecule become
a message? In: Lang A, ed. 28th Symposium of the Society of
Developmental Biology. New York: Academic Press, 1–16.
Pattee, H. H., 2001. The physics of symbols:
bridging the epistemic cut. BioSystems 60:5-21.
Rosen, R., 1991. Life Itself. New York:
Columbia University Press.
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03/24/04 |
Speaker:
Dr. Laura Elnitski,
Dept. of Biology, Penn State University
Title:
"Evolutionary conservation of exonic splicing
enhancer motifs and alternative splicing patterns in whole genome
human-mouse-rat alignments."
Abstract: It is well established that many exons contain internal sequences
that can enhance or repress splicing. We have mapped binding sites
for splicing enhancer machinery on the human-mouse-rat whole genome
alignments for the purpose of identifying potential exonic splicing
enhancers (ESEs)
conserved across the three species. In this approach, specific
binding matrices for 4 ESE motifs, SF2/ASF, SC35, SRp40, and SRp55
[1] were mapped to exons annotated in the April 2003 freeze of the
Human Genome Browser (http://genome.ucsc.edu/). Of
the nearly 5 million conserved binding motifs predicted genome wide,
775,000 intersect with exons. Additionally, we identified
alternative splicing events in human, mouse and rat gene orthologues
using sim4 [2] alignments of the cDNA
sequences in the RefSeq and dbEST databases (http://www.ncbi.nlm.nih.gov) with
the human or rodent genomic sequences. We report the correlation
between the distribution of conserved ESE
motifs and alternatively spliced exons. Furthermore, we provide a
queriable resource that integrates predicted ESE regions and single
nucleotide polymorphisms or other sequence features through our
database called GALA, Genomic Alignments and Annotations [3] which
could assist in the
identification of altered splicing patterns associated with human
disease.
References:
Cartegni, L., J. Wang, Z. Zhu, M. Q. Zhang, and A. R. Krainer, 2003.
ESEfinder: a web resource to identify exonic splicing enhancers,
Nucleic Acid Research 31:3568-3571.
Florea, L., G. Hartzell, Z. Zhang, G. M. Rubin, and W. Miller, 1998.
A computer program for aligning a cDNA sequence with a genomic DNA
sequence, Genome Res. 8:967-974.
Giardine, B., L. Elnitski, C. Riemer, I. Makalowska, S. Schwartz, W.
Miller, and R. C. Hardison, 2003. GALA, a database for genomic
sequence alignments and annotations, Genome Res. 4:732-41.
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03/31/04 |
Speaker:
Wen-Ya Ko, Dept. of
Biology, Penn State University
Title: "Lineage-specific
patterns of molecular evolution in the Drosophila melanogaster
species subgroup."
Abstract: Translational selection at silent sites is well established in many
species. Under the selection-mutation-drift model, the evolutionary
dynamics between major (preferred) and nonmajor (unpreferred) codons
is determined by the selection force favoring major codons and the
mutational pressure changing major codons back to nonmajor codons.
Based on this model, we studied the lineage-specific patterns of
codon usage in six D. melanogaster subgroup species (D,
melanogaster, D. simulans, D, teissieri, D.
yakuba, D. erecta, and D. orena) and two ancestral
lineages (D. teissieri-D. yakuba and D. erecta-D.
orena). From the result of 20 nuclear genes (9515 codons), four
of the eight lineages had a codon usage pattern biased toward
unpreferred substitutions. When each gene was analyzed separately,
this trend was also observed in most of the genes in each of the
four lineages. A significant excess of preferred substitutions was
observed in one lineage although the trend was less consistent among
the genes. The patterns of the other three lineages remain
uncertain due to the lack of a consistent trend in individual
genes. This may indicate that these three lineages are not
significantly departed from the equilibrium. From pairwise
comparisons of the patterns of silent and protein evolutions between
sister species pairs, D. melanogaster has more unpreferred
silent substitutions and faster rates of protein evolution than its
sister species, D. simulans. Studies of major codon usage
patterns in a species would help understand the major cause of
protein evolution if a genome-wide biased codon usage pattern
reflects the demographic history that changes selection
intensities. Future studies will focus on distinguishing the roles
of selection and mutational bias at silent sites and on establishing
the patterns of protein evolution in other sister species pairs.
References:
Akashi, H., 1995. Inferring weak selection from patterns of
polymorphism and divergence at "silent" sites in Drosophila DNA.
Genetics 139:1067-1076.
Akashi, H., 1996. Molecular evolution between Drosophila
melanogaster and D. simulans: reduced codon bias, faster
rates of amino acid substitution, and larger proteins in D.
melanogaster. Genetics 144:1297-1307.
Akashi, H. and S. W. Schaeffer, 1997.
Natural selection and the frequency distributions of "silent" DNA
polymorphism in Drosophila. Genetics 146:295-307.
Begun, D. J. and P. Whitley, 2002.
Molecular population genetics of Xdh and the evolution of
base composition in Drosophila. Genetics 162:1725-1735.
Rodriguez-Trelles, F., R. Tarrio, and
F. J. Ayala, 2000. Fluctuating mutation bias and the evolution of
base composition in Drosophila. J. Mol. Evol. 50:1-10.
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04/07/04 |
Speaker:
Dr. Anton Nekrutenko,
Dept. of Biochemistry and Molecular Biology, Penn State University
Title: "One gene - two proteins."
Abstract: Although genes have been identified for a large number of human
congenital disorders, it is often difficult to pinpoint the
exact molecular mechanism of a disease. In some cases the cause of
the disorder may not be easily discernable because it lies beyond
accepted concepts of molecular biology. One such concept is that
each mammalian gene is thought to encode a protein in just one
reading frame. As a result, if a gene contains an alternative (out
of phase) reading frame (ARF) in addition to the canonical coding
region, this information is treated as erroneous and almost never
included in genetic databases. Thus, it is unavailable to
researchers studying a gene linked to a particular disorder.
However, ARFs can be translated and their disruption may lead to
severe clinical manifestations! A remarkable example of a human gene
encoding two proteins in different reading frames is XLas the
extra long form of the G-protein a-subunit. This gene contains an
~1,000 bp ARF nested within the original coding region. The ARF has
the same orientation as the original coding region but encodes a
protein in a different phase (+1). This arrangement is conserved in
XLas genes from other mammals including mouse, rat and dog. The
resulting mRNA is translated into two proteins that share
no sequence similarity. Interestingly, the two proteins interact
with each other. Disruption of this interaction is linked to a
series of phenotypic effects that include mental retardation and
growth deficiency.
TheXLas exampleprompts
fundamental questions that have never been studied on a genome-wide
scale before: Are there other human genes containing ARFs? Is there
an evidence for a “hidden proteome” consisting of previously
undetected ARF-encoded polypeptides? The answer appears to be “yes”:
in a preliminary study we have identified 81 ARF-containing genes
using a strict set of criteria (ARFs must contain³200 codons and be
conserved in at least two non-primate mammals). Are there human
genetic disorders that may be explained by mutations within ARFs? The
81 genes we have identified are linked to 84 genetic disorders. For
example, the disruption of an ARF in the mammalian X-box binding
protein-1 is linked to severe liver hypoplasia that results in
anemia and in uterodeath.
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04/14/04 |
Speaker:
Dr. James Leebens-Mack,
Dept. of Biology, Penn State University
Title: "The Utility of Whole Chloroplast Genome Sequencing for
Reconstructing Deep Nodes within Basal Angiosperms."
Abstract:
Most recent molecular phylogenies based on one to several genes
have suggested that the monotypic Amborella, or Amborella
plus waterlilies, represents the basal, extant angiosperm lineage.
Last year the chloroplast genome of Amborella was sequenced
and all 61 protein coding genes shared with 12 other available land
plant chloroplast genomes were used to assess its phylogenetic
position. Analyses of both nucleotide and amino acid sequence data
placed the monocot lineage, rather than Amborella, at the
base of the angiosperms. We have sequenced five new chloroplast
genomes to determine if limited taxon sampling could explain this
surprising result. These include two monocots (Acorus and
Yucca), a waterlily (Nuphar), a basal eudicot (Ranunculus),
and a gymnosperm (Ginkgo). Phylogenetic analyses of both
amino acid and nucleotide sequences provided strong support for the
basal position of Amborella, and parametric bootstrap
analyses implicated long-branch attraction in the original study.
References:
Goremykin, VV., K. I. Hirsch-Ernst, S. Wolfl, and F. H. Hellwig,
2003. Analysis of the Amborella trichopoda chloroplast
genome sequence suggests that amborella is not a basal angiosperm. Mol.
Biol. Evol. 20(9):1499-505.
Zanis, M. J., D. E. Soltis, P. S. Soltis, S. Mathews, and M. J.
Donoghue, 2002. The root of the angiosperms revisited. Proc.
Natl. Acad. Sci. USA 99(10):6848-6853.
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04/21/04 |
Dr. Eric Davidson,
Dept. of Biology, California Institute of Biology, CA
The
Department of Biology announces the
Russell Marker Lectures in Evolutionary Biology:
"Evolution and the Genomic
Regulatory
Code for Development"
Wednesday, April 21, 2004 at
8:00 p.m.
Location: Room 101 Thomas Building
Title: “Evolution of Animal Body Plans”
Refreshments to follow.
Thursday, April 22, 2004 at 12:30
p.m.
Location: Kern Building
Auditorium
Title: “Five Hundred Million Years of Echinoderm Evolution:
Comparison of Gene Regulatory Architecture in a Sea Urchin and a
Starfish”
Refreshments to follow.
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04/28/04 |
Bioinformations
Workshop Click
here for powerpoint slides
Location: 310
Rider II Time:
12:00 p.m. (Noon)
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