17 research outputs found
DNA immunoprecipitation semiconductor sequencing (DIP-SC-seq) as a rapid method to generate genome wide epigenetic signatures
Modification of DNA resulting in 5-methylcytosine (5 mC) or 5-hydroxymethylcytosine (5hmC) has been shown to influence the local chromatin environment and affect transcription. Although recent advances in next generation sequencing technology allow researchers to map epigenetic modifications across the genome, such experiments are often time-consuming and cost prohibitive. Here we present a rapid and cost effective method of generating genome wide DNA modification maps utilising commercially available semiconductor based technology (DNA immunoprecipitation semiconductor sequencing; “DIP-SC-seq”) on the Ion Proton sequencer. Focussing on the 5hmC mark we demonstrate, by directly comparing with alternative sequencing strategies, that this platform can successfully generate genome wide 5hmC patterns from as little as 500 ng of genomic DNA in less than 4 days. Such a method can therefore facilitate the rapid generation of multiple genome wide epigenetic datasets
Structure-Based Virtual Screening for Drug Discovery: a Problem-Centric Review
Structure-based virtual screening (SBVS) has been widely applied in early-stage drug discovery. From a problem-centric perspective, we reviewed the recent advances and applications in SBVS with a special focus on docking-based virtual screening. We emphasized the researchers’ practical efforts in real projects by understanding the ligand-target binding interactions as a premise. We also highlighted the recent progress in developing target-biased scoring functions by optimizing current generic scoring functions toward certain target classes, as well as in developing novel ones by means of machine learning techniques
Therapeutic use of plants by local communities in and around Rema-Kalenga Wildlife Sanctuary: implications for protected area management in Bangladesh
DNA immunoprecipitation semiconductor sequencing (DIP-SC-seq) as a rapid method to generate genome wide epigenetic signatures
Chemical
modification
of
the
cytosine
base
via
the
addition
of
a
methyl
group
to
form
5-‐methylcytosine
(5-‐mC)
is
a
well-‐studied
example
of
an
epigenetic
mark,
which
contributes
to
regulation
of
gene
expression,
chromatin
organisation
and
other
such
cellular
processes
without
affecting
the
underlying
DNA
sequence.
In
recent
years
it
was
shown
that
5-‐mC
is
not
the
only
DNA
modification
found
within
the
vertebrate
genome.
5-‐hydroxymethylcytosine
(5-‐hmC)
was
first
described
in
1952
although
it
wasn’t
until
2009
when
it
was
rediscovered
in
mammalian
tissues
that
it
sparked
intense
interest
in
the
field.
Research
has
found
that
unlike
the
5-‐mC
base
from
which
it
is
derived,
5-‐hmC
displays
variable
levels
and
patterns
across
a
multitude
of
tissue
and
cell
types.
As
such
the
patterns
of
these
DNA
modifications
can
act
as
an
identifier
of
cell
state.
This
thesis
aims
to
characterize
the
methyl
and
hydroxymethyl
profiles
of
induced
pluripotent
stem
cells
(iPSCs),
derived
from
control
mouse
embryonic
fibroblast
cell
line
(p53-‐/-‐)
as
well
as
and
methylation
hypomorphic
(p53-‐/-‐,
Dnmt1
-‐/-‐)
mutant
cell
lines.
As
such
both
somatic
cells
were
subject
to
reprogramming
with
Yamanaka
factors
(Oct4,
cMyc,
Klf4
and
Sox2)
via
the
piggyback
transposition
technique.
Successful
reprogramming
was
confirmed
by
a
number
of
techniques
and
outcomes,
including
the
de
novo
expression
of
a
number
of
key
pluripotency
related
factors
(Nanog,
Sall4
and
Gdf3).
Reprogrammed
cells
were
then
analysed
for
transcriptomic
changes
as
well
as
alterations
to
their
methyl
and
hydroxymethyl
landscapes
that
accompany
reprogramming.
Through
this
work
I
have
shown
that
the
reprogramming
of
MEF
derived
cell
lines
results
in
a
global
increase
in
5-‐hmC
for
both
p53-‐/-‐
and
(p53-‐/-‐,
Dnmt1
-‐/-‐)
hypomorphic
mutant
cell
lines
–
possibly
through
the
reactivation
of
an
alternative
form
of
DNMT1.
I
demonstrate
by
both
antibody
based
dot
blot
assay
and
genome
wide
sequencing
that
the
reprogramming
of
the
(p53-‐/-‐,
Dnmt1
-‐/-‐)
somatic
cells
towards
a
pluripotent
state
brings
about
an
increase
in
methylation
levels
within
the
cells.
This
latter
observation
may
indicate
that
the
reprogramming
of
the
cells
is
driving
them
towards
a
more
wild
type
phenotypic
state.
My
studies
suggest
that
lack
of
DNMT1
function
is
not
a
barrier
to
reprogramming
of
somatic
cells
Translation rotation elevation osteotomy of the spine of the scapula for treatment of impingement syndrome and incomplete cuff tears
The dual role of the extracellular matrix in synaptic plasticity and homeostasis
Recent studies have deepened our understanding of multiple mechanisms by which extracellular matrix (ECM) molecules regulate various aspects of synaptic plasticity and have strengthened a link between the ECM and learning and memory. New findings also support the view that the ECM is important for homeostatic processes, such as scaling of synaptic responses, metaplasticity and stabilization of synaptic connectivity. Activity-dependent modification of the ECM affects the formation of dendritic filopodia and the growth of dendritic spines. Thus, the ECM has a dual role as a promoter of structural and functional plasticity and as a degradable stabilizer of neural microcircuits. Both of these aspects are likely to be important for mental health