Physiological And Pathological Systems Within The...

Physiological And Pathological Systems Within The...
Redox signalling is an electron transfer process that is crucial in biological systems. Redox
signalling is found in many physiological and pathological systems within the circulatory system.
Redox signalling is usually induced by an overproduction of reactive oxygen species (ROS) which
can alter the functions of cell processes. Harris,(2012). ROS are radicals that contain one or more
unpaired electrons and can be the oxygen radical superoxide or the non–radical hydrogen peroxide
(H2O2). ROS can also contribute to vascular modelling by phenotype modification of the smooth
muscle cells, growth and even the death of cells. This shows the need for redox signalling and it has
many roles within the body. Harris. (2012). Redox signalling is important as exposure to oxidative
stress can cause imbalances that can contribute to infections and toxins. Thiol based redox couples
can form independent signals that can regulate any imbalances and are linked to any changes that
occur in redox potentials. Harris. (2012). Cysteine is an amino acid and it can undergo oxidative
modifications to perform different functions. Cysteine can form cross links to stabilise proteins and
it functions as a reversible on/off switch in redox signalling. Paget,(2003). Cysteine is a nucleophile
that can react under different conditions, due to the thiol functional group. Conte,et al. (2000).
Thiols contain sulphur and hydrogen and this gives them a higher acidity than alcohols. . Redox
cysteine thiols
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Coma Membrane: Lipid Rafts
Lipid rafts are defined as the subdomains of the plasma membrane that exist as distinct liquid–
ordered regions of the membrane [1]. These membrane domains preferentially arise due to the
interaction of specific lipids. They are mobile, dynamic and insoluble in non–ionic detergents such
as Triton X–100 [2]. Lipid rafts are enriched in cholesterol, sphingolipids and phospholipids within
cell membranes (Figure 1).
Figure 1. Organization of lipid rafts (Note the higher concentration of cholesterol and sphingolipids)
within the raft region. (Image: WikiBooks Structural Biochemistry/Lipids/Lipid Rafts).
Sphingomyelin (SM) (also called ceramide phosphocholine), a type of sphingolipid, is a ubiquitous
component of the animal membrane [3].The major sources of sphingomyelin are the bovine brain,
egg yolk and milk [4]. It is, being analogous of phosphatidylcholine, typically consists of a ceramide
unit with a phosphocholine moiety attached to position 1. A typical example of sphingomyelin is a
d18:1/16:0 molecular species: ... Show more content on Helpwriting.net ...
These lipid rafts have been proposed to serve many functions in cell signalling, membrane
trafficking and signal transduction [7]. There are some special types of proteins (e.g.,
transmembrane proteins and GPI–anchored proteins) that can anchor on the nanodomains to play an
important role in transporting chemicals through the membrane [8]. Sphingomyelin rich rafts act as
hotspots or platforms to enable transmembrane proteins to aggregate so that they can promote cell
signalling events

Spleen Tyrosinse
Spleen tyrosine kinase (SYK) is a cytoplasmic non–receptor tyrosine kinase that has been shown to
be involved in intracellular signaling pathways of a number of diverse cell types. Structurally, SYK
is a 72k Da protein with two SRC homology 2 domains and a kinase domain. It has a well–
documented and crucial role in intracellular signaling of adaptive immune cells via immunoreceptor
tyrosine–based activation motifs (ITAMs) of the classical immunoreceptors; B cell receptors, T cell
receptors and Fc receptors. Activation of these receptors leads to the phosphorylation of the ITAMs'
cytoplasmic tyrosine residues resulting in the recruitment and activation of SYK. For activation,
both of SYK's SH2 domains needs to bind to the phosphorylated ITAMs of the receptor, or
phosphorylation can occur at a tyrosine residue in either of the interdomains. This initial
phosphorylation leads to the autophosphorylation of other tyrosine residues in the interdomains or
the kinase domain, resulting in ITAM release and sustained activation.
Following ITAM activation, SYK has been shown to complex with several different intermediate
molecules. This results in the triggering of varying responses including phagocytosis, Ca2+
signaling, cytoskeletal rearrangement, reactive oxygen species (ROS) production, and protein ...
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These PRRs include hemITAM containing C–type lectins resulting in ROS production,
phagocytosis, and gene transcription. SYK has been shown to activate the ERK signaling cascade
and activate NF– κB resulting in proinflammatory responses. This includes the SYK dependent and
NF– κB mediated production of pro–IL–1β and the its proteolytic processing by Caspase 1 in
inflammasomes, a multiprotein complex. The inflammasome activation is also regulated by the SYK
dependent activation of nod–like receptor family pyrin domain–containing 3 (NLRP3) reported in
antifungal immune

Ligand Cell Biochemistry
Reception is the target cell's detection of the signal via binding of a signaling molecule, or ligand.
Ligand is a complex biomolecule, usually a protein. Receptor proteins span the cell's plasma
membrane and provide specific sites for water–soluble signaling molecules to bind to Receptors are
found in two places; Intracellular proteins are found inside the plasma membrane in the cytoplasm
or nucleus.Cell–surface proteins are embedded in the plasma membrane These transmembrane
receptors are able to transmit information from outside the cell to the inside because they can
transform, when a specific ligand binds to it.
Transduction is a process which occurs when the receptor protein binds to a signalling molecule,
which will lead to a series of changes in the receptor which in turn changes series of different
molecules along a signal–transduction pathway. The molecules in the pathway are called relay
molecules. The multistep process of the transduction stage is often composed of the activation of
proteins by the addition or removal of phosphate groups or even the release of other small molecules
or ... Show more content on Helpwriting.net ...
A response can occur in three steps which include any cellular activity, rearrangement of the
cytoskeleton, or catalysis by an enzyme. These three steps of cell signaling all ensure that the right
cells are behaving as told, at the right time.cell signalling leads to the regulation of transcription or
cytoplasmic activities. Many signalling pathways ultimately affect protein synthesis, usually by
turning specific genes on or off within the nucleus. Often, the final activated molecule in a
signalling pathway functions as a transcription factor. In the cytoplasm, signalling pathways often
regulate the activity of proteins rather than their synthesis. For example, the final step in the
signalling pathway may affect the activity of enzymes or cause cytoskeleton

Marfan Syndrome: Connective Tissue
Marfan syndrome is a histological disorder that specifically deals with one of the four primary types
of tissue known as connective tissue. Marfan syndrome is also considered an autosomal dominant
disease, meaning this disorder requires only one parent or donor to carry the abnormal gene for it to
be inherited in the offspring. The inheritance of the abnormal gene is the biological basis or genetic
trigger that results in a mutation that occurs in the gene named fibrillin–1, or short FBN1. The
respective location of gene FBN1 is on chromosome 15. Function of the FBN1 gene includes storing
the blueprints for making the glycoprotein fibrillin–1, which is a component of many tissues. When
produced, the fibrillin–1 protein exits the cell via transport

My research interests lie in cell signaling, and more...
My research interests lie in cell signaling, and more broadly, in sensory processing. My interest in
cell signaling has evolved from early studies I conducted on the human A1 adenosine receptor
(hA1AR). In this first exposure to G–protein coupled receptor (GPCR) signaling, I aided in
determining those amino acid residues within the fifth transmembrane–spanning region of the
hA1AR that were accessible from the ligand–binding crevice using the substituted–cysteine
accessibility method (SCAM). Utilization of SCAM entailed modification of the native hA1AR
receptor by mutating single amino acids in the targeted GPCR region to cysteine. So altered GPCRs
were then allowed to react with hydrophilic, cysteine–specific methanethiosulfonate ... Show more
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elegans). To do this I participated in the design and creation of a Par–6 green fluorescent protein
(GFP) expressing transgenic nematode. I cloned the par6 gene from an existing C. elegans cDNA
library and fused the product to GFP. I also performed in vitro pull down and in vitro kinase assays
to determine whether Par–6 protein complexes with proteins implicated in calcium signaling.
Most recently I performed research to identify key proteins involved in the termination of the
signaling pathway of intrinsically photosensitive retinal ganglion cell (ipRGCs). The distinctive
photoreceptive properties exhibited by ipRGCs are due to the activity of the GPCR, melanopsin,
which is expressed in these cells. I contributed to our knowledge of melanopsin signaling by aiding
in the identification of an isoform of the downstream effector phospholipase C by conducting the
immunohistochemical experiments that confirmed the RT–PCR and physiological data collected by
my colleagues. This work was published in the 2008 article "Melanopsin Ganglion Cells Use a
Membrane–Associated Rhabdomeric Phototransduction Cascade".
Little information existed regarding termination of the pathway however and to address this
deficiency, I used both biochemical and electrophysiological techniques in a body of work that
culminated in my doctoral thesis. By introducing a series of mutations into C–terminal tail of
melanopsin, I was able to

Biochemistry: Transmembrane Receptors
Cells use receptors to recognize a signal, and each signal has a specific receptor ("Cell Signaling").
Receptors bind to signal molecules that act as ligands, molecules that bind to another molecule
which cause the receptor to change shapes ("Cell Signaling"; Urry et al. 109). Receptors are usually
transmembrane proteins located on the plasma membrane which includes enzyme–linked receptors,
ion channel receptors, and G–protein coupled receptors. These receptors use the signals received to
affect the function of the cell without harming the cell. Enzyme–linked proteins are typically
activated by enzymes ("Cell Signaling"). Ion channel receptors open and close, allowing specific
ions to move in and out ("Ion Channel.") An example of an ion channel receptor is a ligand–gated
ion channel which is important for the nervous system. The largest group of transmembrane
receptors are G–protein coupled receptors or GPCRs. GPCRs use a G protein that bind GTP. These
receptors have many functions including embryonic development and helping with taste and smell
(Urry et al. 110). Cells use the receptors on the outside of the cell, but cells also use receptors on the
inside. ... Show more content on Helpwriting.net ...
These receptors are found in the cytoplasm or the nucleus. Before the messenger with the signal can
reach the receptor, it must first be able to pass through the plasma membrane. The signaling
molecules are hydrophobic, which help it pass through the hydrophobic part of the membrane. For
examples, animals have steroid hormones and thyroid hormones that are hydrophobic so the
hormones can go through the plasma membrane. A cell must have the particular receptor in order for
it to be activated. Testosterone can enter cells all over the body, but only the cells with the receptor
will actually use it (Urry et al. 110–111). CLINCHER

Supramolecular Architecture Of Rhodopsin Captured By The...
Based on the supramolecular architecture of rhodopsin captured by the AFM image and available
crystallographic data, in 2003 the first model of higher order organization of a GPCR in its native
membrane was derived implicating involvement of transmembrane domains in contact formation
between neighboring rhodopsin molecules within the dimer as well as between distinct rows of
dimers (Liang et al., 2003). This model suggested that the intradimeric contacts defining primary
dimer interface involve transmembrane helices 4 (TM4) and 5 (TM5), whereas the formation of
rhodopsin dimer rows is facilitated by the interaction between helices 1 (TM1) and 2 (TM2).
Interestingly, a structure of squid rhodopsin, solved soon after, agreed with TM4/TM5 dimer very
well (Murakami and Kouyama, 2008). Different experimental strategies have been further applied to
identify rhodopsin dimer interface to validate this semi–empirical rhodopsin–packing model. Firstly,
cysteine mutagenesis of specific amino acids predicted by molecular modeling to be involved in
formation of the dimer–contacting surface followed by intermolecular crosslinking in the presence
of cupric orthophenanthroline (CuP) let to the identification of two amino acids Trp175 and Tyr 206
at the dimer interface of opsin heterologously expressed in membranes of COS1 cells (Kota et al.,
2006b). Trp175 is present in the extracellular loop connecting TM4 and TM5 and Tyr206 is located
on the extracellular side of TM5 therefore

Brown Adipose Tissue (BAT)
Brown adipose tissue (BAT) is derived from the mesenchymal precursor cell which also seems to
give rise to muscle . BATis located mainly around the neck, paravertebral sites, kidneys and large
blood vessels of the thorax. As previously mentioned above, Marcus (1988), demonstrated that TSH
induced lipolysis in BAT from newborns and infants but this declined with age. Recent studies have
profiled different layers of BAT in adults, particularly in the neck and between the shoulder blades
(Nedergaard, 2013). BAT contains multilocular lipid droplets and a high mitochondrial content. Its
primary function is to liberate energy as heat via the consumption of stored energy. This is mediated
by the uncoupling protein–1 (Ucp–1), which embeds in the inner mitochondrial membrane and
produces heat by dissipating the proton electrochemical gradient over the inner mitochondrial
membrane space without generating ATP. The energy in BAT? is stored as perilipin coated lipid
droplets and glycogen granules. Upon temperature stimulation glucose and fatty acid uptake is
rapidly increased to replenish its supplies (reviewed in Sanchez–Gurmaches, 2013).
BRITE adipose tissue occurs within WAT tissue depots, in response to chronic cold exposure. Beige
adipose tissue has the characteristics of both white and brown adipocytes. They appear to be like
WAT in basal states but upon cold stimulation, they behave like BAT by becoming multilocular and
expressing the brown fat marker UCP1. However, they are

Ryanodine Receptors Research Paper
The Ryanodine receptors (RyRs) are membrane proteins that are located in the sarcoplasmic and
endoplasmic reticulum of the cells. The key role of the receptors is to mediate the release of calcium
ions (Ca2+) from intracellular storages in either reticulum into the cytoplasm during excitation–
contraction coupling in muscles. Intracellular Ca2+ regulation is important for secondary messenger
for signal transduction and is essential for certain cellular processes. Ryanodine is named after the
plant alkaloid ryanodine, which binds to the receptors and displays preferential interactions with the
open state of the channel. At nanomole concentrations, they lock the Ca2+ channel in an open sub–
conductance state and at higher concentration, they inhibit the channels completely. For mammalian
organisms, there are three distinct RyRs are the largest known ion channels and three isoforms have
been identified, RyR1, RyR2 and RyR3 each of which is encoded by a distinct gene on different
chromosomes (Lanner, Georgiou, Joshi, & ... Show more content on Helpwriting.net ...
They interact with and are regulated by phosphorylation, redox modifications, and a variety of small
proteins and ions. Most of the RyR channel are modulated through interactions with the large
cytoplasmic domain whereas the carboxy–terminal portion of the protein forms the ion–conducting
pore. As RyRs have such large structures, multiple modulators, and the dynamic nature, it makes
high–resolution structural analysis a challenge. While some details of RyRs has been obtained
through x–ray crystallography among others, much of the protein dynamic is still unknown. As it is
known that RyRs consist of fifteen distinct domains per subunit, there should be a focus on the
individual domains and regions of the protein in order to facilitate studying of the structure
functions (Lanner, Georgiou, Joshi, & Hamilton,

Types Of Cell Surface Receptors And The Mitogen Activated...
Introduction–
Cell–surface receptors are integral membrane proteins that play a major role in signal transduction,
allowing the function of Neurons, muscles and sensory organs to occur. Their basic function is to
carry out the process of signal transduction by binding to an extracellular signalling molecule. Cell–
surface receptors regulate gene transcription, ion flux in the neurons and growth factors. This
regulation allows the human body to function with little error. They detect the smallest of changes
and respond with a cascade of signalling events appropriately. I am going to describe the four main
types of cell–surface receptors and the Mitogen–activated protein cascade in receptor tyrosine
kinases.
G–Protein Coupled Receptors– ... Show more content on Helpwriting.net ...
GPCRs consist of alpha–helical segments separated by these intracellular and extracellular loops
(Figure 1) Figure 1 Structure of G–protein–coupled receptor, showing alpha–helical proteins
attached to the three subunits of the G–protein.
GPCRs are associated with a G protein, which is heterotrimeric i.e. they consist of three different
subunits: an alpha subunit, a beta subunit, and a gamma subunit (Figure 1). (Scitable by nature) G
proteins are specialized proteins with the ability to catalyse the exchange of guanosine triphosphate
(GTP) and guanosine diphosphate (GDP). (Scitable by nature)
The G–protein receptor is coupled to a trimeric G protein and controls the effector protein. The
receptors activate cytosolic or nuclear transcription via several pathways. They are involved in
signal transduction pathways such as MAP kinase pathway. (Lodish et al.).
When a signalling molecule such as Epinephrine, serotine and adenosine is released and binds to the
extracellular receptor site of the GPCR, the G protein changes conformation and GTP replaces the
GDP on the alpha subunit of the G–protein (Figure 2). This activated alpha subunit then parts from
the beta and gamma subunits. The alpha subunit becomes inactive when the ligand leaves the
receptor site and the receptors own phosphorylase activity removes a phosphate from the GTP
molecule, therefore leaving GDP bound to the alpha–subunit and the reformation of the 3 subunits.
Figure

How Do ROS Influence Gene Expression And Synthesis?
ROS play beneficial or harmful role based on the balance between their generation and
detoxification (Abouzari and fakheri, 2015). In plants, under optimal concentration and
physiological conditions they take part in pathogen defense, programmed cell death, senescence,
cell signaling, gene regulation and so on (Hammond–Kosack and Jones, 1996; Grant and Loake,
2000; Breusegem et al., 2001: Blokhina et al., 2003; Laloi et al., 2004; Gechev et al., 2006).
Superoxide and hydrogen peroxide in particular and ROS in general serve as intracellular signaling
molecules (Scandalios, 2005) and regulate a great deal of intracellular signaling pathways (Sauer et
al., 2001). Moreover, they are crucial secondary messengers (Saed–Moucheshi et al., 2014). ROS
influence gene expression in three ways. ... Show more content on Helpwriting.net ...
Second, they may oxidize signaling pathways directly. And third, ROS may target and modify
transcription factors where the eventual effect may bring about change in gene expression.
Furthermore, ROS activate MAPK signaling cascades which is central for mediating cellular
responses to multiple stresses (Abouzari and fakheri, 2015). They do so through Calcium ion (Ca2+)
(Price et al., 1994). Furthermore, key signaling proteins such as tyrosine phosphatase sense ROS
directly through the oxidation of conserved cysteine residues (Xiong et al., 2002). On the other
hand, ROS take part in redox cycling of cysteinyl thiols which is crucial to establish protein–protein
and protein–DNA

The Critical Medical Issue of Type 2 Diabetes Mellitus
Type 2 Diabetes Mellitus (T2DM)
Diabetes is one the most critical medical issues of our time. According to the Center of Disease
Control and Prevention nearly 26 million Americans (approximately 8% of all Americans) have
diabetes and an estimated of 79 million adults are pre–diabetes. Approximately $200 billion per year
is lost due to diabetes because of medical treatments and lost wages. Insulin resistance and the
dysfunction of beta cells are the two pathogenic hallmarks of the development and progression of
T2DM. Studies have shown that pancreatic beta cell functional mass is affected in T2DM (1, 2).
Secretion of insulin stimulated by glucose is lower in human islets of Langerhans isolated from
patients with T2DM than from normal individuals (1, 3). Knowledge of the molecular mechanism
underlying defects in beta cell function found in humans and animal models of T2DM is incomplete.
Without a more complete understanding of the mechanisms that regulate beta cell insulin secretion
we will be unable to develop new approaches to prevent and treat diabetes.
Physiological aspects of beta cell function Beta cells of the endocrine pancreas constantly monitor
glucose levels circulating in the blood and respond accordingly by releasing insulin. Glucose is the
primary physiological stimulus of insulin secretion. When blood glucose concentration is elevated,
glucose is transported across the beta cell plasma membrane by passive diffusion through glucose
transporters (GLUT–1

What Is The Role Of Mechanisms In The Cells?
In cells, the process of producing and releasing a particular chemical, whether a protein or some
other regulatory molecule, often requires the presence of an external signal. Cells must therefore
have specialized receptors for this signal, or ligand. There are several classes of cell surface
receptors, including receptors with noncatalytic activity, such as G protein–coupled receptors, and
those with catalytic activity such as receptor tyrosine kinases.
The former helps transduce a signal across the plasma membrane through second messenger
systems, including adenylate cyclase. This results in a signaling cascade. First, a signaling molecule
binds to the G protein–coupled receptor, causing the G protein alpha subunit to exchange GDP for ...
Once the necessary transcription factors are activated, the cell initiates transcription of the relevant
gene(s). After transcription and processing in the nucleus, the mature mRNA migrates to the cytosol,
where it is recruited by a ribosome to initiate translation. A series of steps allow the free ribosome to
become associated with the endoplasmic reticulum to allow for the release of the synthesized protein
into the rough endoplasmic reticulum (ER).
First, a signal recognition particle (SRP) binds to the signal peptide as it emerges from the ribosome.
SRP then binds to a receptor on the rough ER surface, which allows the ribosome to bind as well.
Once on the rough ER surface, the ribosome resumes translation and feeds the polypeptide through
the pore and into the rough ER cistern. A signal peptidase, which is associated wit the pore, snips off
the signal peptide. Translation continues, and the growing polypeptide slides into the rough ER
cistern while remaining attached to the ribosome on the surface. The completed polypeptide is then
released into the rough ER cistern, where it floats freely before further processing takes place (Karp
& Patton, 2013).
Processing involves the folding of the protein into its functional three–dimensional conformation.
This folding is aided by molecular chaperones inside the rough ER. Additional modifications may
take place, including attaching short sugar chains to the protein for the formation of glycoproteins
(Karp & Patton,

Heterotrimeric Meaning Pathway
Describe the signalling pathways downstream of the heterotrimeric G proteins Gs, Gi and Gq.
Heterotrimeric G–proteins are an important group of proteins involved in signal transduction and are
associated with G–protein coupled receptors (GPCR). These proteins bind to guanine nucleotides:
guanosine triphosphate (GTP) and guanosine diphosphate (GDP). Gs, Gi and Gq are the three
different G–protein families that exists.
G–proteins are have three subunits, alpha (), beta () and gamma (), each composed of different
amino acid therefore they are known as heterotrimeric. The G and G are tightly attached to each
other so are known as the beta–gamma complex (G). G subunit has an important feature which is the
binding site for exchange of GTP to GDP.

The Filoviridae Family Corresponds To The Order Of...
The filoviridae family corresponds to the order of Mononegavirales. This growing family of
pathogens are filamentous, enveloped viruses with a genome that is negative–stranded RNA (1
& 2). This family is known to be one of the most pathogenic viruses affecting humans and is mostly
found in bats (their main reservoirs) (3 & 4). It is believed that these viruses are transmitted from
person to person through body fluids or through objects that have been previously contaminated
with body fluids (5). After transmission and incubation period (three to
21 days), the initial symptoms are headache, fever, vomiting and diarrhea. After, the virus may cause
viraemia, coagulopathy, haermoorhagic fever and liver/ multi–organ failure; which in many cases ...
The envelopes of EBOV and MARV are composed of glycoproteins (GP). GP are essential for the
entry of the viruses into the host cell by attaching to its cell surface (10). GP is a homotrimer of GP1
(membrane protein) – GP2 (transmembrane protein) heterodimer linked by disulfide bonds (11 &
12). The mechanism on how GP1 and GP2 drive the introduction of the virus into the host cell is not
well understood yet (7). However, it is known that is characterized by three steps: attachment,
uptake, and membrane fusion (7). GP1 is involved in adhesion of the receptor with the host cell
surface, whereas GP2 is involved in the virus–host cell membrane fusion and entry (13). In most
cases GP1 is believed to bind to different glycosaminoglycans
(GAG) from the host cell i.e. heparin sulfate, to be able to efficiently enter the host cell (2).
GAGs are negative, unbranched polysaccharides found in mostly all cells surfaces but differ in
composition between species (4). It is believed that GAGs are not the only possible way of
attachment for filoviruses to the host surface, meaning that there are other host factors that aid in
viral entry (2). After attachment, virions get into the host cell through micropinocytosis followed by
endosome trafficking which leads to membrane fusion (7). A low pH due to the endosomal events is
what leads to the initiation of membrane fusion (7).
G protein–coupled receptors (GPCR) are the biggest and most diverse family of protein in

Yeast Communication Lab
Purpose In this experiment, we were trying to find out how yeast cells manage to communicate and
thus mate asexually in order to produce offspring. In order for a message to be communicated, a
signal must be sent and then received by another being; this lab will prove how yeast cells go
through this communication process in order to produce a required response for the production of
yeast. Background Information: Both unicellular and multicellular organisms use cell
communication in order to elicit a response which helps an organism coordinate and respond to their
environment. Cellular communication can occur through direct contact, local signaling, or long–
distance signaling. For a response to occur, a message much reach a receptor that ... Show more
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This makes sense, as this is a very secure environment in which yeast can thrive. Although yeast can
reproduce when there is only one reproductive type present, best results are achieved when there is a
mix. It is always better to recombine DNA and increase genetic variability than to have many others
have the same DNA. It leads to a higher survival rate for the species, because one genetic defect
cannot wipe out the entire species. Based on our results we conclude that alpha–type yeast has more
of the mating factor signal released by yeast cells to asexually reproduce because alpha type had a
much higher percentage of budding haploid cells. We also concluded that when alpha and a–type
cultures of yeast are mixed they communicate by both chemical signals and direct contact to
sexually reproduce with each

Physiology 1 Ch-4,5
Physiology 1 ch–4,5
1. ___________ is a term which describes a membrane that allows only certain molecules to
penetrate it.
A. Selective permeable
B. Permeable
C. Porous
D. Counter transport
2. Active Transport
A. Utilizes energy
B. Cannot transport molecules against a concentration gradient.
C. Cannot be saturated
D. Requires cofactors
3. The Rate of diffusion is influenced by
A. The concentration gradient
B. Membrane permeability
C. Membrane surface area
D. All of the choices are correct
4. Cells placed in hypotonic solutions will
A. Decrease in volume
B. Increase intracellular solute concentration
C. Increase in volume
D. Loose water to the solution
5. Protein carrier mediated transport of molecules display
A. Specificity
B. ... Show more content on Helpwriting.net ...
All of the choices are correct.
20. Which of the following is able to passively penetrate the plasma membrane?
A. O2
B. Small charged particles

C. Large polar molecules
D. All of the choices are correct.
21.Ion channels that can be opened by physiological stimuli are said to be
A. Polar
B. Aquaporins
C. Hypertonic
D. Gated
22. A cell placed in a hypertonic solution would
A. Lyse
B. Crenate
C. Not change
D. Swell
23. Receptors for intercellular messengers are most commonly
A. Peripheral membrane proteins
B. Integral membrane proteins
C. Specialized phospholipids with in the membrane
D. Nucleic Acids
24.Which of the following are common means by which binding of an intercellular chemical
messenger with a cell's receptor brings about an intracellular response?
A. Opening or closing of specific ionic channels in the plasma membrane
B. Activation of an intracellular second–messenger system
C. Promoting or inhibiting the transcription of genes that code for the synthesis of cellular proteins
intracellular second–messenger system are correct
D. All of the choices are correct.
25. Activation of a receptor by a chemical messenger
A. Occurs when the messenger binds to the ligand–binding site of the receptor
B. Is the first step leading to the ultimate response of a cell to the messenger
C. Requires a change in receptor conformation
D. Both occur when me messenger binds to the ligand–binding site of the receptor

The Development of Heart Failure
1–Introduction
Intro– Heart Failure is a multifactorial disease due to significant diminishing of heart pumping
action. This is occurs in response to many underlying disease such as diabetes, hypertension,
myocardial infarction and cardiac myopathies. These conditons lead to hemodynamic instability,
neuroendocrine imbalances and structural remodeling of cardiac myocytes. Early less sever hf
allows for compensatory mechanisms such as neuroendocrine stimulation– (beta adrenbergic r
endothelin norepinephrine r), and hypertrophy which allow for sufficient left ventricular pumping
action. However as hf develops these mechanisms become unable to compensate for the progressive
underlying disease which results in further loss of contraction and relaxation efficiency and loss of
regulation.
Ca roles– apoptosis, hypertrophic growth, signal transduction pathway– etcs– gene transcriptional
and essential in ecc, regulate pacemaking– LOSS OF CALCIUM HOMEOSTASIS IN THE
CARDIAC MYOCYTE HAS SIGNIFICANT EFFECTS ON THESE DIFFERENT PROCESSES
and can have many pathological impliocations
I will specifically focus on the how ca regulation is affected in signal transduction pathways and ecc
which are the main changes in the cardiac myocyte.
ECC– IMPAIRED FORCE DEVELOPMENT, SLOWER RELAXATION AND PROLONGATION
OF AP DURATION
CAIN signaling transduction pathways – affects many ca dependent signalling proteins whic leads
to downstream Hypertophic growth and gene trancscription– (impaired

Insulin Resistance and Exercise Essay
This is a discussion of research article listed at end of paper
When muscle is damaged, there is a general resistance to insulin. The physiological stress that is
associated with damaged muscle impairs how insulin stimulates IRS–1, PI 3–kinase, and Akt–
kinase. This presumably leads to less glucose absorption. Previous studies have shown that there has
been temporary insulin resistance due to the physiological stress associated with muscle damage.
However, the molecular mechanisms by which physiological stress induces insulin resistance is not
known.
The many effects that insulin has on metabolism and cellular growth begin when insulin binds to its
receptor at the cell membrane. The insulin signals from the insulin receptor is ... Show more content
on Helpwriting.net ...
This has been associated with elevated production of mononuclear cell derived cytokines. This
includes tumor necrosis factor alpha (TNF–alpha), interleukin 6 and interleukin 1–Beta. TNF–alpha
impairs insulin signal transduction in muscle cells. * Also, in vivo administration of TNF–alpha in
animals imparis glucose uptake by the whole body and skeletal muscle.
Supporting the data on the link between TNF–alpha and insulin is the fact that neutralization of
TNF–alpha in animal models of insulin resistance resulted in a significant increase in insulin action.
This has led to intense speculation that TNF–alpha may play a role in type 2 diabetes.
This study explored the potential role of TNF–alpha in the inhibition of insulin action after limited
human muscle damage.
The purpose of this study was to find the effects of muscle damage on insulin signal transduction at
the level of the enzymes, which are critical steps in the regulation of insulin action and insulin–
mediated glucose uptake. Also, a first attempt was made in finding the extent to which TNF–alpha is
associated with temporary insulin resistance after muscle damage in human subjects.
Cell signaling is a burgeoning new field of interest in biology. The study of this signaling reveals the
nature of the infinitesimal, and the manner in which our cells coordinate to properly undergo certain
functions.

Pharmacodynamics (Drug Receptors)
Dose of drug administered ABSORPTION DISTRIBUTION Drug in tissues Drug in systemic
circulation Pharmacokinetics Drug metabolized or excreted ELIMINATION Drug at site of action
Pharmacologic effect Pharmacodynamics Toxicity Efficacy PHARMACOLOGY
Pharmacodynamics Actions of drug on the body  Specific to a drug/ class of drugs Interaction with
target sites (receptors/enzymes) Effects at site of action Dose–response relationship Reduction in
symptoms Modification of disease process Unwanted/side effects Drug interactions Inter– and intra–
patient differences Pharmacokinetics Actions of body on the drug  Non–specific, general processes
Absorption from site of administration Distribution to the ... Show more content on Helpwriting.net
...
Effects of ligand produced after a characteristic lag period of 30 mins to several hours  This is the
time required for synthesis of new proteins  Hence gene–active hormones cannot be expected to
alter a pathologic state within minutes 2. Effects of these agents can persist for hours or days after
agonist concentration in the body has been reduced to zero  Main Reason: Relatively slow
turnover of most enzymes & proteins ⇒ They can remain in cells for hours or days after synthesis 
Partially due to high affinity of receptors for hormone ⇒ Slow dissociation of hormone (2) Ligand
– Regulated Transmembrane Enzymes  Receptors are polypeptides Consist of: 1. Extracellular
ligand–binding site 2. Cytoplasmic enzyme/ catalyic domain.   The cytoplasmic enzyme/
catalytic domain may be: › Tyrosine kinase › Serine Kinase › Guanylyl cyclase  Agonist binds to
receptor's extracellular domain  Change in receptor conformation  Two receptor polypeptides
bind together (Inactive monomeric state is converted to an active dimeric state)  Tyrosine residues
in the cytoplasmic domains become phosphorylated  Tyrosine kinase is activated  Binding &
phosphorylation of SH2 domain protein  Activation of various intracellular signalling pathways
 Responses tend to occur over minutes to hours Examples of such receptors › Insulin receptors
› Growth factor receptors  (3) Ligand – gated ion channels

Statement Of Purpose For Organic Chemistry
"Imagination is the highest form of research." I first felt thrilled in pursuing scientific research,
when I learned about critical aspect of materials chemistry in the elucidation of nanoparticles for
drug delivery systems in organic chemistry with Prof. Sunasee. Since then, I host a passion for
academic and research traing designed to prepare me for graduate studies in the development of
nanomaterials and nanotechnologies for healthcare. My primary research interests are in the fields of
nanotechnology and materials chemistry for drug therapy and cancer biology (of the p53 and pro–
apoptotic signal transduction pathways).
Academic and Research Background:
Organic Chemistry has always been a source of great fun and challenge to me. As a result of my
earnest passion for the subject and outstanding record (third rank in the class out 93 students & first
rank in the laboratory out 24 students), I was selected to participate as summer teaching assistant in
organic chemistry, and received the honor to join Dr. Sunasee's Research Lab. My time as summer
teaching assistant enriched my academic experience in teaching and peer tutoring and also advanced
my skills in chemistry. ... Show more content on Helpwriting.net ...
Rajesh Sunasee, I worked on the synthesis and characterization of cellulose nanocrystals (CNC) for
biomedical applications, and assessed toxicological levels of various CNC and MACA compounds.
Our research target nanocrystals carriers with low toxicity levels and molecular dimensions with
potential to improve drug delivery and therapeutic efficacy. With this experience, I gained an
understanding of how interdisciplinary research is essential to creating progress in modern
medicine, such as in the field of

Bevacizumab : An Anti Vegf Recombinant Humanized Igg ¬ 1...
Bevacizumab is an anti–VEGF recombinant humanized IgG¬1 monoclonal antibody (rhuMAb)
angiogenesis inhibitor that is indicated as supplemental chemotherapy for metastatic cancers
including colorectal carcinoma, breast cancer, and renal cell carcinoma, as well as advanced non–
squamous non–small cell lung cancer.1,3,4 It has also been approved as a second–line single agent
therapy for glioblastoma multiform.3,4 Characteristic to all IgG monoclonal antibodies is the
presence of two fragment–antigen binding (Fab) domains that are covalently bound to a constant
(Fc) region.2 Bevacizumab is available for intravenous administration after dilution with 0.9%
Sodium Chloride Injection USP with recommended dosing regimens ranging from 5 mg/kg to 15
mg/kg every 2–3 weeks, depending on the type of malignancy.3,4
Mechanism of Action
Overexpression of vascular endothelial growth factor (VEGF) promotes development of tumor–
supportive vasculature, cell survival and migration, and vascular permeability. The expression of
VEGF is regulated via several mechanisms including oxygen tension, autocrine and paracrine
signaling, and oncogenic signaling.5 VEGF is a homodimeric glycoprotein that binds to VEGF
receptors 1 and 2 (VEGFR–1 & VEGFR–2) with high affinity (K¬d ~ 1–10 pM and Kd ~ 10–100
pM, respectively) on the extracellular surface of endothelial cells.5,7 Activation of VGFR, a tyrosine
kinase receptor, prompts receptor dimerization and autophosphorylation that initiates signal
transduction

Phospholipids Essay
Lipids are well–known as essential constituents of living cells. Phospholipids, a class of complex
lipids, serves as the building blocks of almost all cellular membranes by forming the lipid bilayer
and thus maintains cell shape and integrity (Bollag, 2016). Phospholipids are also rich sources of
important cellular intermediates that plays role in cell development, metabolism, and signaling
(Hong et al., 2016). The composition and content of phospholipids varies among different
membranes and typically changes during development and in response to different stress cues (Hong
et al., 2016). Similar to most eukaryotes, fungi also possesses phospholipid based plasma membrane
and intracellular organelles. The most abundant classes of phospholipids found in fungi includes
phosphatidylcholine (PC) and phosphatidylethanolamine (PE) while phosphatidylserine (PS),
phosphatidylinositol (PI), phosphatidylglycerol (PG), diphosphatidylglycerol (cardiolipin), and
lyso–derivatives of PC and PE are found only in minor amounts (Dembitskii and Pechenkina, ...
Phospholipases are ubiquitous enzymes that hydrolyses phospholipids mainly glycerophospholipids
and also neutral lipids into various signaling products which includes phosphatidic acid (PA),
diacylglycerol (DAG), free fatty acids (FFAs), and lysophospholipids (LPLs) that are involved in
regulating numerous processes such as cytoskeletal dynamics, homeostasis, membrane remodeling,
microbial virulence, nutrient acquisition, secretion and signal transduction (Kohler et al., 2006;
Hong et al.,

Essay On Hbx X Protein
Hepatitis B virus x protein (HBx) is one of four encoded proteins in the Hepatitis B virus (HBV)
genome. HBx is encoded by the smallest open reading frame of mammalian hepadnaviruses which
produces a 154–amino acid protein with a molecular mass of 17.5 kDa. HBx has defied high–
resolution crystallization and nuclear magnetic resonance so little is known of HBx three–
dimensional structure (an implication that HBx is unstructured). HBx also lacks homology with any
other known protein so there is poor understanding of how it functions. Comparative analysis of
HBx gene sequences from mammalian hepadnaviruses of different species has highlighted areas
where the sequence is highly conserved. This includes predicted helical domains located in the ...
Research suggests that when HBx interacts with cellular proteins it dimerizes; however, this remains
speculative. Three articles (Gao et al., Elmore et al. and Zhu et al.) have been selected to highlight
some of the key carcinogenic effects of the HBx protein.
MicroRNA–145 (miR–145) expression shows an inhibitory effect on the proliferation of human
cancer cells. In HCC, the expression of miR–145 was found to be significantly downregulated as a
result of HBx interaction. Gao et al. identified Cullin–5 (CUL5) as a target of miR–145. CUL5 has
been reported to be functionally involved in numerous cellular activities including the cell cycle. In
addition, CUL5 was also reported to be involved in regulating apoptosis by modulating the
phosphorylation of mitogen–activated protein kinase (MAPK) and induce p53 mRNA and protein
expression. The substantial increase in the expression of CUL5, due to the inhibition of a miRNA–
145 expression by HBx, results in less phosphorylation of MAPK and therefore less p53 mRNA and
protein expression. This study confirmed a significant decrease in the expression of miRNA–145
and a substantial increase in the mRNA and protein expression of CUL5 in HBx–over–expressing
cells compared with empty vector–transfected cells. The proliferation of the cells transfected with
HBX plasmid markedly increased compared with cells transfected with empty vector.
The p53 tumor suppressor protein is involved in many cellular

To Contribution To Hematopoietic Cell Development And The...
Introduction
The ability to respond to external signaling is an inherent property of all mammalian cells. External
stimuli could be in the form of hormones or mitogens and can lead to further intracellular signaling
pathways that trigger cellular changes. This internal mechanism of communication is essential to the
development of an organism and plays a critical role in growth, homeostasis and cellular defense
system. Among the various pathways that regulate cellular functions, JAK/STAT pathway is one that
allows communication between membrane receptors and the nucleus. Extensive studies of this
pathway have led us to understand gene expression via nuclear signaling. JAK/STAT significantly
contributes to hematopoietic cell development and ... Show more content on Helpwriting.net ...
Once STAT has been phosphorylated it can recruit other STAT units to itself forming homodimers or
heterodimers. Dimerization of STAT proteins allows the homodimer/heterodimer to be translocated
to the nucleus where it then binds to gamma activated sequence (GAS) elements within the nucleus.
Binding of STAT proteins to GAS elements in the DNA leads to the transcription of target genes
which ultimately play a crucial role in cellular viability, survival, apoptosis, etc. (1,2) Activation of
the JAK/STAT pathway is responsible for initiation of multiple signal transduction cascades such as
Ras–Raf–MEK–Erk, PI3K–Akt–mTOR and phospholipase C–γ.
Excessive stimulation of cytokine regulated cascades is seldom unaccompanied by adverse events.
Negative regulation as such is accomplished by protein tyrosine phosphatases (e.g. SHP–1, CD45)
which act by removing phosphates from phosphorylated proteins, suppressor of cytokine signaling
proteins (SOCS) that competitively inhibit STAT phosphorylation by binding or inhibiting JAKs and
the protein inhibitors of STATs (PIAS) which block the binding sites of STATs in the DNA thereby
inhibiting the transcriptional activation (3).
Implications of JAK–STAT in disease
So far, we have seen that this pathway is accountable for the transduction of extracellular stimulus
into transcriptional factors that regulate several cellular functions.

Different Methods Of Communicating Between Cells And Humans
As multicellular organisms became more complex they required a method of communication
between cells. Over time several methods of cell–cell communication developed. There are two
main methods of communicating between cells in humans. One is a humoral method that usually
involves hormones or other ligands (molecules that bind to larger molecules) that are released into
the blood stream and then cause a response in the target cell. The other method is by using nerve
cells an electrical signal is transferred across a large distance and will then result in a response.
Hormones are proteins whose structure is shaped in order to interact with a cells surface membrane.
They are specific to cell surface receptors and will only trigger a change in cell that has a particular
receptor. Because of this the body can communicate with certain types of call selectively as it can
produce a hormone specific to the receptors on that cell group. This is an advantage to a human as it
is a complex organism and as a result many types of cell that require coordinating in different ways.
Therefore having different hormones for different signals helps to avoid disorientation of the cells
making the organism more efficient.
Hormones are usually produced in a specific type of cell or gland. For example the hormone insulin
is only produced in Beta cells of the islets of Langerhans in the pancreas, the hormone travels into
the blood stream through the capillary network where it's distributed across the

Taste Receptor Cells Lab Report
Discussion The Classes of Taste Receptor Cells There are various TCRs involved in the detection of
the different taste qualities. These TRCs are primarily located in taste buds, which are found in
raised papillae across the tongue. There are approximately 5,000 taste buds within the oral cavity,
each containing over a hundred TRCs (4). TRCs are polarized neuroepithelial cells. Their apical tips
are exposed to the external environment and are in close proximity with sensory nerve endings.
TRCs are divided into three major classes: type I glial–like cells, type II receptor cells and type III
presynaptic cells (5). Type I cells, the most abundant of TCRs, have always been considered to
function solely as supportive cells, thus resembling glial cells of the CNS. Similar to glial cells, type
I cells are affiliated with both ATP and glutamate hydrolysis and uptake. Additionally, they wrap
their membranes around other cells (5). Type I cells have also been described as containing only
voltage–gated, ... Show more content on Helpwriting.net ...
The N–terminal of T1R2s extracellular domains functions in a similar manner to that of a Venus
Flytrap. The N–terminal is necessary for the detection of sweeteners, such as aspartame. The T1R3's
C–terminal domain plays a vital role in recognizing additional sweeteners, such as cyclamate, and
surprisingly the sweet taste inhibitor lactisole (9). Research and experimentation concludes that a
dimer of T1R1 and T1R3 has the ability to detect L–amino acids, which constitute umami tastes.
Furthermore, sweet tastes are sensed by the T1R2 and T1R3 dimer (11). T1R3s are used with sweet
and umami taste receptors. Buried within the transmemrane helices are the binding sites of T2Rs.
This characteristic allows them to be suitable for detecting nonpolar, bitter tastants. Structural
differences between T1Rs and T2Rs allow each of them to uniquely bind to the varying tastes
(Figure

A Brief Note On Mediates Contact Dependent Homophilic
Dscam:
Mediates contact–dependent homophilic repulsion
Dscam diversity underlies a robust cellular recognition mechanism allowing dendrites to distinguish
between surfaces of different cells.
Main arguments is that Dscam–mediated self avoidance is a general organizing mechanism
operating throughout Drosophila nervous system.
da neurons associate closely with the epidermis as they extend across the body wall; thus, their
dendrites create a two–dimensional meshwork in which developing branches frequently encounter
other dendrites (different from CNS where axons and dendrites form 3D by interaction)
when deficient in Dscam function, individual dendrites do not recognize sister branches and fail to
initiate repulsion, leading to a ... Show more content on Helpwriting.net ...
Dscam is required for proper segregation of sister axon branches (Wang et al., 2002), and analogous
to the self–avoidance control in da neurons, specific isoforms do not appear to provide instructive
cues for this segregation event. It has been argued that this reflects a role for Dscam in mediating
self–recognition and repulsion between these axons
In da neurons, dendrite selfavoidance defects were separable from growth, branching, and targeting
errors and were fully penetrant. Thus, our data directly implicate Dscam in self–avoidance and
demonstrate this role at the level of interactions between individual branches.
Mechanism:
identical Dscam ectodomains on the surfaces of isoneuronal dendrites recognize each other and
induce a subsequent repulsive signal that is mediated by domains in the cytoplasmic tail.
How: o First, identical Dscam isoforms expressed in two cell populations in vitro induced their
aggregation in an isoform–specific manner, showing that Dscam provides cells with the ability to
distinguish between different cell surfaces. o Second, ectopic (in an abnormal place or position)
expression of identical Dscam isoforms on the dendrites of different cells, which normally overlap,
promoted growth away from each other.
From in vitro adhesion to in vivo repulsion
Our data suggest that the dendrites of da neurons convert an initial Dscam–dependent cell–surface
interaction into a repulsive response, which leads to dendrite separation and receptive

Different Types Of Stresses From The Internal And External...
Throughout the lifetime of a living organism, it is exposed to many different types of stresses from
the internal and external environment. In order to maintain homeostasis, cells must be poised to
activate appropriate cellular stress responses to overcome the initial stress stimulus. Mitogen–
activated protein kinase (MAPK) pathways are crucial among the major pathways that regulate
stress responses. There are six conserved and ubiquitous MAPK signalling pathways in mammalian
systems that coordinate and integrate responses to various stimuli. The architecture of each pathway
is conserved, with the 'core signalling module' consisting of a phosphorylation cascade which is
mediated by three classes of protein kinases: the MAPK kinase kinase (MAP3K), the MAPK kinase
(MAP2K) and the MAPK. Within this pathway, the MAP3K is activated or inactivated by various
stimuli resulting in the successive phosphorylation and activation of MAP2K, which in turn
phosphorylates and activates MAPK. Activated MAPK's then regulate the appropriate cellular
responses by activating or inactivating cellular targets, such as other protein kinases or transcription
factors. Due to the position of MAP3K's at the apex of the 'core signalling module', it is important to
understand their regulatory mechanisms as the MAPK pathway is dependent on their activation.
Apoptosis signal–regulating kinase 1 (ASK1) is a MAP3K family member. This MAP3K is
activated in response to a host of cellular stress stimuli,

SKBR3 Cells : Positive And Negative Cell Cycles
SKBR3 and MCF–7 used as HER2 positive and negative cell line respectively. The cytotoxic effect
of of scFv(Herceptin)–PE–stxa recombinant immunotoxin carried out by MTT assay. The cytotoxic
action of scFv(Herceptin)–PE–stxa has obviously revealed target–specific cell killing. SKBR3 cells
demonstrated high suseptibility to scFv(Herceptin)–PE–stxa whereas MCF7 was not reactive at low
concentration but at higher concentrations showed low cytotoxicity. Since the cytotoxic segment is
conserved in STXA, the only determinant factor that makes scFv(Herceptin)–PE–stxa a strong killer
is the specific binding domain, scFv(herceptin), which binds to HER2 on the cell membrane. A
different cytotoxic action of scFv(Herceptin)–PE–stxa was also seen among ... Show more content
on Helpwriting.net ...
Moreover, the features of the targeting domain, shed antigen levels are apparently an element in the
potential therapeutic use of targeted agents(22). The mechanism of cell death stimulated by
scFv(Herceptin)–PE–stxa –immunotoxin has not been fully understood, though it is proposed that
apoptosis induction icontributes to this process.
In the current study flow cytometry was used for determination of scFv(Herceptin)–PE–stxa
immunotoxin cell death mechanism. phosphatidylserine (PS) residues in normal cells are seen in the
inner membrane of the cytoplasmic membrane. In the apoptosis event the PS residues are transferred
to the membrane and are externalized. Generally, though not always, this is an primary event in the
apoptosis and a signal is sent to the surrounding cells that a cell is ready for phagocytosis. Annexin–
V is a special PS–binding protein that is used for detection of apoptotic cells(26).
It has been reported that STXA can induce apoptosis by different mechanisms.
Following binding of FV fragment of immunotoxin to the cell receptor, the immunotoxin receptor
complex is internalized and locates within the endosomes. Instead of going to lysosomes for
degradation, the complex traffics in a retrograde manner within the cell through the Golgi system to
the ER(27).
The STXA–subunit cleaves by a furin–like protease, and actived A1 subunit is released into the
cytoplasm and performs its effect on ribosomes(28). Alternatively, there is documented that
uptacked STX–Gb3

Cyytoprotective Role Of DJ-1, Mitophagy And Cell Death
DJ–1 protects against mtDNA damage, mitophagy and cell death. DJ–1 is a multifunctional protein
that protects cells from oxidative stress via several molecular processes including regulating gene
transcription, mediating cell signal transduction pathways, stabilizing cytoprotective proteins and
scavenging ROS (3). DJ–1 is expressed in human primary alveolar type II cells (preliminary data)
and we have recently postulated that plays a role in the antioxidant defense system in the lung
(REF). The importance of DJ–1 can be supported by several observations. First, DJ–1 mutations are
pathogenic (4), second, oxidation of cysteine and methionine residues within DJ–1 was reported as a
sensor of its activity (5) and third, the novel oxidized ... Show more content on Helpwriting.net ...
Research Plan
Preliminary Results
Isolation of human primary ATII cells.
We will isolate ATII cells from de–identified control organ donors whose lungs were not suitable for
transplantation and donated for medical research through Temple Biobank in collaboration with Dr.
Gerard Criner (Temple University, letter attached) as we previously described (7, 9, 10). For ATII
cell isolation, we used magnetic microbeads (Miltenyi, Biotec Inc.) and epithelial cell adhesion
molecule (Ep–CAM) positive selection. Purified ATII cells display about 90% purity as detected by
staining with pro–surfactant protein C (proSP–C) and ATII280, which are specific ATII cell markers
(Fig. 2). In this grant proposal, we plan to use ATII cells isolated from at least 12 non–smoker and
12 smoker control lung donors and 12 patients with emphysema (GOLD IV). Lung tissue from
individuals with this disease will be obtained in collaboration with Dr. Criner.
DJ–1–Cys106–SO3– in patients with emphysema. Initial proof of concept studies were performed in
ATII cells obtained from patients with emphysema in comparison with control lung donors. We
found high expression of DJ–1–Cys106–SO3– in ATII cells obtained from individuals with this
disease using a specific DJ–1 antibody (AbDSerotec; Fig. 3). The presence of this DJ–1 form was
confirmed by mass spectrometry analysis; and we did not find this modification in control ATII

Vascular Endothelial Development
ABSTRACT:
The disclosure of the vascular endothelial development component (VEGF) relatives VEGF, VEGF–
B, placental development variable (PlGF),VEGF–C and VEGF–D and their receptors VEGFR–1, –
2 and – 3 has given devices to contemplating the vascular framework being developed and
additionally in illnesses going from ischemic coronary illness to malignancy. VEGF has been built
up as the prime angiogenic particle amid advancement, grown–up physiology and pathology.
VEGF–C and VEGF–D are basically lymphangiogenic elements, however they can likewise impel
angiogenesis in a few conditions. While numerous studies have tended to the part of angiogenesis
and the blood vasculature in human physiology, the lymphatic vascular framework has as of not
long ... Show more content on Helpwriting.net ...
As of late VEGF expression has been exhibited in heart myofibroblasts, non–endothelial cells with
the morphological elements of fibroblasts. Myofibroblasts assume a noteworthy part in the
development, improvement and repair of typical tissue and are found at the site of localized
necrosis. RT–PCR, Northern blot and Western blot investigation affirmed the vicinity of mRNA and
protein for VEGF, VEGFR–1 (VEGF receptor 1 otherwise called Flt–1, fms–like tyrosine kinase)
and VEGFR–2 (KDR/Flk–1, fetal liver kinase 1 is the murine homologue of human Kinase embed
Area containing Receptor) in rodent myofibroblasts segregated from heart infarcts.10 Coexpression
of VEGF and its receptors on the myofibroblasts proposes that VEGF adds to tissue rebuilding at the
site of dead tissue in an autocrine way. VEGF might likewise assume a part in atherosclerosis.
Uptake of oxidized low–thickness lipoprotein (bull LDL) by macrophages starts froth cell
development in atherosclerotic sores. Oxidized LDL expanded VEGF creation by the U937
monocyte cell line and by macrophages. As VEGF likewise increments vascular penetrability,
VEGF creation by froth cells and macrophages may bother atherosclerosis by improving vessel
porousness to

What Role Do Kidneys Play In The Human Body
Kidneys play a major role in the human body. The kidneys perform a number of functions including
removing waste products and other fluids from the body as urine. In this project, the main focus is
Polycystic kidney disease. In cystic kidney disease, fluid–filled cysts form in the kidneys, usually in
the weaker segments of tubules, that perform the duty of carrying urine from the glomeruli. As a
cyst grows, it displaces healthy kidney tissues and as a result the kidneys have to expand to
accommodate the cyst. The normal cell signaling pathway of a healthy kidney includes the three
Ca2+ entry pathways, the PC1/PC2, L–type/T–type, and others. PC 1 and 2 are encoding
polycystins, L–type and T–type are calcium channels, and the others are also calcium channels as
well. As the Ca2+ enters, it goes through P13K, which is an enzyme that is involved in cellular
functions. Next, it moves on to Akt, which is a ... Show more content on Helpwriting.net ...
At the G–protein– coupled receptor proteolytic site, the N terminus of PC1 is cleaved, but the
extracellular domain is still noncovalently attached to the membrane–bound portion of the protein.
The two different cleavages release C–terminal tail fragments that move to the nucleus with parts of
the Wnt pathway, STAT6/p100, and with other regulators of transcription. PC2 stimulates one of the
C–terminal tail cleavages. This requires the PC2 to be able to function as an ion channel. Both direct
and indirect interactions allow the polycystin proteins (PC) to inhibit and/or stimulate pathways
involved in cell division and growth. If there are defects in the gene encoding of either PC1 or PC2
it can lead to unusual ion secretion, gene transcription, and cell proliferation, which can then result
in the formation of fluid–filled cysts. As a cyst begins to grow bigger it leads to the displacement of
the normal kidney functions. Also the formation of the cyst in the kidneys reduce its functional

Prevention of Leukemic Stem Cells Developing from...
PROJECT TITLE: Prevention of Leukemic Stem Cells developing from Hematopoietic Stem Cells
by targeting the Ras/Raf/MEK/ERK pathways
INVESTIGATOR: Michelle Nguyen (Spring 2014)
PROJECT SUMMARY: According to the study done in 2014 by the National Cancer Institute,
leukemia is the 11th most common type of cancer (Howlader et al., 2011). This cancer that originate
in the bone marrow or other tissues that form blood cells causing them to divide rapidly without any
control (Wu, 2012). These leukemia stem cells are derived from hematopoietic stem cells but
because of high telomerase activity, the stem cells have the ability to self–renew limitlessly (Heidel,
Mar, & Armstrong, 2011). As of right now, there are many treatments available such as ... Show
more content on Helpwriting.net ...
To confirm the efficiency of the drug, the drugs will administered to NOD/SCID mice with
leukemic properties and effects will be monitored.
RELEVANCE: The most common form of the blood cancer is the production of white blood cells.
This buildup of these white blood cells hinders the body from control bleeding, supplying oxygen to
the tissues, removing waste from tissues, and to fight infections. Approximately, someone in the US
dies from a blood cancer every ten minutes. Of the blood cancers, leukemia accounts for 33% of the
deaths (Siegel, Naishadham, & Jemal, 2013). Because the cancer stems from a transformation from
healthy hematopoietic stem cells to leukemic stem cells, it would be beneficial to treat the disease
with a stem cell therapy. The purpose of this study is to understand the mechanism of how
hematopoietic stem cells are turned into leukemia stem cells and be able to prevent the
transformation. It will be another step for researchers to find a less invasive method of threating
leukemia that is safe for all ages and severity. The understanding of which factors induce the
conversion of how HSCs to LSCs and being able to prevent it opens doors to new therapies and
treatments and make stem cell transplants more safe and widely available.
RESEARCH PLAN:
Hypothesis: By understanding the pathways that dictate the mechanism that causes a hematopoietic
stem cell to mutate into a leukemic stem cell, an inhibitor/antagonist

Retinal Photoreceptor Rhodopsin: A G-Protein Receptor...
G–protein–coupled receptors (GPCRs) are membrane proteins that provide a molecular link
between extracellular signals and intracellular processes. The retinal photoreceptor Rhodopsin (Rho)
is one of the prime examples of the G–protein–coupled receptor superfamily which is a visual
pigment which absorbs photons and initiates G–protein signal transduction processes that result in
electrical signals processed by the brain. Rod cells, containing rhodopsin in their outer segments,
mediate vision by responding to dim levels of light. Cone opsins are proteins related to rhodopsin
and are present in cone cells. These proteins also use 11–cis–retinal as a chromophore, but their
absorption maxima are located at wavelengths different from that of ... Show more content on
Helpwriting.net ...
Helix VII is a short helical segment on the cytoplasmic side of the membrane oriented parallel to the
membrane surface.
Two short β strands are located on the extracellular side of the protein near the retinal binding site.
11–cis–retinal serves as a cofactor for rhodopsin. In the inactive/ground state the prosthetic group
forms a covalent Schiff base linkage with the amine group of Lys296 in helix VII. At the other end
of the chromophore, in the activated form of the protein, Glu113 on helix III gets protonated serving
as a counter–ion for it. The retinal is located between the helices towards the extracellular side of the
protein and is completely buried within the protein by the extracellular loops. The transducin
binding site is some distance from the cytoplasmic surface and amino acid side chains from the
transmembrane helices block access to that surface.
The most significant states of the photoreceptor rhodopsin are the light–sensitive ground state
metarhodopsin I and the active state metarhodopsin II which binds and activates the G–protein. The
shift between these two states is operated by cis–/trans–isomerization of the chromophore retinal
followed by thermal relaxation and proton transfer reactions. Ground–state rhodopsin is inactive,
and this state is restrained by its structural features. Interactions among the extracellular loops,
including a disulfide bridge, limit the conformation flexibility of this

Molecular and Cellular Behavior
Signal transduction pathways link signal reception with cellular response
Signal transduction pathways regulate what occurs in, between, and amid individual cells. They are
incredibly crucial because they initiate large responses beginning with a single signal. These
chemical signals are called ligands that enter the cell either through active or passive transport. If the
ligand is small and nonpolar (such as nitric oxide, oxygen gas, and carbon dioxide), then it will
simply diffuse through the cell membrane and will attach to an intracellular receptor. However, if
the ligand does not fit into this category it will attach to a membrane receptor. These ligands are
specific to each receptor. This ensures that no ligand will bind to an incorrect receptor. Once a
receptor is bound, a signal is transduced in a way that the cell can acknowledge it. Signal
transduction pathways will fundamentally affect gene expression, change enzyme or protein activity,
and possibly cell death.
Membrane Receptors
Membrane receptors span the membrane of the cell. Since hydrophilic molecules cannot simply
diffuse through the cells to send a signal to the cell, they must attach to these receptors to be able to
send a signal inside the cell.
Ligand –Gated Ion channel receptor
Specific signal molecules open and close ion channel receptors that permit the passing of ions in and
out of the cell. These ions include Na+, K+, Ca2+, or Cl–, necessary for sending chemical signals.
G–protein–coupled

Cytokines : Causes And Complications Of The Policiune System
Generally, the term cytokine describes the families of secreted proteins that regulate multiple
biological processes, including the innate and adaptive responses of the immune system (Steinke
2013, Sacca 2017, Dinarello 2000). They regulate these responses by performing a multitude of
important functions in the cells of the body, and lead to growth, differentiation and activation in
their targets (Steinke 2013). Each cytokine family fulfills one or many specific roles in the immune
system, for example the stimulation of lymphocyte growth or the promotion of inflammation
(Steinke 2013, Sacca 2017).
Pro–inflammatory cytokines are those which – among several other negative consequences –
promote inflammation and tissue destruction ... Show more content on Helpwriting.net ...
The cytokine is produced upon initiation of the inflammatory response (Gabay 2006). Here, IL–6
binds to the IL–6 receptor – which is composed of two subunits (Ni 2004). The α subunit of the IL–
6 receptor carries the glycoprotein gp130 – one of the primary signal–transducers involved in the
immune response, found on both the soluble and membrane–bound IL–6 receptors (Ni 2004,
Scheller 2014). The IL–6/IL–6R complex initiates a proteolytic cascade which proceeds to activate
the JAK2 kinases of the JAK/STAT signal transduction pathway (Ni 2004). The activated JAK2
kinases phosphorylate signal transducers and activators of transcription (STATs), which activates
transcription factors downstream (Rane 2000, Schindler 1995). The transcription factors pair to form
a dimer and subsequently migrate to the nucleus to activate the gene transcription (Ni 2004). As a
result, the proteolytic cascade initiated by the IL–6/IL–6R complex up–regulates inflammatory
mediators and innate immune responses and regulates the expression of genes involved in
inflammation, apoptosis, and oxidative stress (Erta 2012, Sacca 2017). Under normal conditions,
IL–6 is produced by macrophages, and in endothelial cells and T–cells in response to pathogen–
associated molecular patterns (PAMPs) and damage–associated molecular patterns (DAMPs)
(Abbas 2015, Dowalti 2010). It is therefore produced at the

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