Fibroblast Growth Factors (FGFs) in Neural Induction

Fibroblast Growth Factors (FGFs) in Neural Induction Abstract Neural induction represents the first stage in the formation of the vertebrate nervous system from embryonic ectoderm. Fibroblast Growth Factors (FGFs), initially identified for their mitogenic and angiogenic roles in bovine brain extracts, are now known to have many developmental roles in particular that of neural induction, comprising of a family of 22 FGFs. Spemann and Mangold (1924) pioneered the study of neural induction through the identification of the organizer. Early work in amphibians suggested that neural fate was instructed by signals from Spemanns organiser or dorsal mesoderm. Over a decade ago, the default model proposed that neural induction was the direct consequence from inhibition of bone morphogenetic proteins (BMPs) found in Xenopus laevis, not taking into consideration neural induction in avian embryos. Consequently many experimental studies, in the chick, subsequent to this finding conflicted the idea that BMP inhibition was the only necessary step required suggesting that FGFs were required at an earlier stage prior to BMP inhibition. Much controversy has surrounded the role of FGFs in neural induction but now it is widely accepted to have a role in both amphibians and amniotes. Fibroblast Growth Factors in neural induction Structure and Function: FGFs broken down Fibroblast Growth Factors (FGFs) regulate a vast array of developmental processes, including, limb development, neural induction and neural development (Bà ¶ttcher and Niehrs, 2005). FGFs play an important role in development of an organism by regulating cellular differentiation, proliferation and migration and are involved in tissue-injury repair (Itoh and Ornitz, 2004). The early FGFs, FGF1 and FGF2 (also known as acidic and basic FGF, respectively) were first discovered from bovine brain and pituitary extracts and identified for their mitogenic and angiogenic activities (Gospodarowicz et al., 1974). Additionally, a number of family members were found revealing a total of 22 FGFs in humans ranging from 17 to 34 kDa in molecular mass in vertebrates. The nomenclature extends to FGF23 but in humans FGF19 is the equivalent to mouse Fgf15 (Ornitz and Itoh, 2001). Also the FGFs have been organised into seven subfamilies based on sequence comparisons. FGFs show conservation through species, especially across the vertebrate species in gene structure and amino-acid sequence. FGF sequences are yet to be found in unicellular organisms such as yeast (Saccharomyces cerevisiae) and bacteria (Escherichia Coli) (Itoh and Ornitz, 2004). Interestingly, an Fgf-like gene has been encoded in the nuclear polyhedrosis virus genome (Ayres et al., 1994). In protostomes, there are far fewer FGFs in contrast to vertebrates, as two (let-756 and egl-17) have been found in Caenorhabditis elegans and three (branchless, pyramus and thisbe) in Drosophila (Mason, 2007). Most FGFs have amino-terminal signal peptides (Fig. 1 (a)) and are secreted from cells. FGFs 9, 16 and 20 lack this signal peptide but nevertheless are still secreted (Ornitz and Itoh, 2001). FGF1 and FGF2 lack these signal sequences and are secreted by non-canonical pathways, however they can be found on the cell surface and within the extracellular matrix. Golfarb (2005) suggests that FGFs 11-14 do not interact with FGF receptors (FGFRs) and are not secreted but instead localise to the cell nucleus. Fig. 1 (above) illustrates the structural features of the FGF polypeptide (a). A signal sequence (shaded grey) can be seen here within the amino terminus and is present in most FGFs. All FGFs contain a core region (Fig. 1 (a)) containing around 120 amino acids of which 6 are identical amino acids residues and 28 are highly conserved (Goldfarb, 1996). The black boxes (numbered 1 to 12) represent the location of ÃŽ ² strands within the core. The three dimensional structure of FGF2 (b) can also be seen where the heparin binding region (yellow) includes residues between ÃŽ ²1 and ÃŽ ²2 strands and in ÃŽ ²10 and ÃŽ ²11 strands. FGFs have a high affinity for heparan sulfate proteoglycans (HSPG) and require heparan sulphate to activate one of four transmembrane receptor tyrosine kinases (FGFR1-4) in all vertebrates. FGFR5 has been identified recently, however most action is mediated via FGFR1-4 (Powers et al., 2000). FGFRs are membrane associated class IV receptor tyrosine kinases (RTKs). The FGFR tyrosine kinase receptors (Fig. 2 B) include 3 immunoglobulin (Ig) domains and a heparin binding sequence which requires heparan sulphate to be activated (McKeehan et al., 1998). HSPG are low affinity receptors that are unable to transmit a biological signal but act as co-factors for activation and regulation of an interaction between FGFs and FGFRs. Fig. 2 (above) illustrates a two dimensional generic FGF (A) and a FGFR (B) protein. The structure of a FGF (A) coincides with that of Fig. 1, containing a signal sequence in the amino-terminus and the conserved core region containing HSPG and receptor-binding sites. The main features of FGFRs (B) include 3-Immunoglobulin domains, an acidic box (AB) which lies between IgI and IgII, heparin-binding domain, Cell Adhesion Molecule (CAM)-homology domain, transmembrane domain and a split tyrosine kinase enzyme domain for catalytic activity and binding of adaptor proteins. The Ig domains in the extracellular region of a FGFR are required for FGF binding and regulate binding affinity and ligand specificity. Multiple alternative splicing that generates a range of FGFR1-4 receptor isoforms with transformed ligand binding properties provides diversity (Olsen et al., 2006). For example, FGF2 interacts with all four receptors FGFR1-4 whereas FGF7 only interacts with the FGFR2 IIIb isoform (a splice variant of FGF2; expressed in epithelial cells). Ligand-receptor binding specificity is affected by alternative splicing particularly in the C-terminal region of the third immunoglobulin loop in FGFR1-3 which produces IIIb or IIIc isoforms (Mason, 2007). Table 1 (below) illustrates the specificity of the FGF ligands for particular FGFR isoforms. This table is useful yet evidence from in vitro may appear misleading as in vivo involves influence from co-factors such as HSPG (Mohammadi et al., 2005). Table 1 (above) shows there are seven FGFR isoforms (FGFR1b; FGFR1c; FGFR2b; FGFR2c; FGFR3b; FGFR3c and FGFR4) that FGF1 through to FGF23 variously bind. Alternative mRNA splicing of FGFR1-3, particularly in the carboxy-terminal half of the third extracellular immunoglobulin loop (Ig-domain III), derives the b and c isoforms. HSPGs are necessary co-factors in activation of FGFRs by FGFs and evidence has found the ternary complex to comprise of FGF-FGFR-HSPG in a 2:2:1 ratio (Mohammadi et al., 2005). The co-binding of HSPG prevents proteolysis and thermal denaturation (Itoh and Ornitz, 2004). HSPG binding of FGF induces dimerization of FGFR, followed by transphosphorylation of receptor subunits, initiating an intracellular signalling cascade. FGF signalling: Its a cellular game Following formation of the FGF-HSPG-FGFR complex several downstream signalling pathways are activated (Fig. 3 below). This includes three pathways, the Ras/Mitogen-activated protein kinase (MAPK) pathway, Phosphoinositide 3-kinase (PI3K)/ Akt pathway and phospholipase C- (PLC )/ Ca2+/ protein kinase C (PKC) pathway. These pathways are mediated via docking proteins (such as FGF receptor substrate (FRS) and Grb2 in the Ras/MAPK pathway) that recruit downstream enzymes. The Ras/MAPK pathway (Fig. 3) is initiated via Grb2 (a docking protein) where its SH2 domain binds to the tyrosine phosphorylated FRS2 in response to activation of the FGFR receptor (Kouhara et al., 1997). Grb2 binds to SOS (son of sevenless; a guanine nucleotide exchange factor) via a SH3 domain on the Grb2 molecule. This Grb2-SOS complex activates SOS which promotes the dissociation of GDP from Ras so it is able to bind GTP for its activation. Activated Ras activates RAF (MAPKKK) which is normally held in a closed conf ormation by the 14-3-3 protein. Once activated, RAF phosphorylates and activates mitogen-activated and extracellular signal-regulated kinase (MEK (MAPKK)) which in turn phosphorylates ERK1/2 (MAPK). MAPK then translocates into the nucleus to phosphorylate specific transcription factors of the Ets family which in turn activate expression of FGF target genes. In addition, it is also evident from Fig. 3 that active ERK itself can antagonise FRS activity. Activation of the PI3K/Akt pathway (Fig. 3) is by binding of Gab1 (Grb2-associated-binding protein 1) to FRS2 indirectly via Grb2. In the presence of Gab1, activation of PI3K stimulates the Akt pathway which suggests FGFs have anti-apoptotic effects in the developing nervous system (Mason, 2007). In addition, PI3K can bind to a phosphorylated tyrosine residue of FGFR directly. The third way in which the PI3K/Akt pathway is activated is by activated Ras inducing membrane localisation of the PI3K catalytic subunit. PLC- /Ca2+/PKC pathway is also activated when a tyrosine residue is autophosphorylated in the carboxy terminal of the FGFR. PLC- hydrolyses phosphatidylinositol to produce inositol trisphosphate (IP3) and diacylglycerol (DAG) which stimulates calcium release and activates PKC, respectively. PKC has also been found to activate the Ras/MAPK pathway independent of Ras but dependent on c-Raf (Ueda et al., 1996). Fig. 3 also indicated that the final activated components, of the three signalling pathways mentioned, translocate into the nucleus to activate specific transcription factors of the Ets family (particularly Ets1, Pea3, and Erm) which activate expression of FGF target genes and in turn these feedback (Fig, 4) to regulate intracellular signalling (Dailey et al., 2005). Most of the proteins produced function as feedback inhibitors (as seen in Fig. 4), including Sprouty (Spry), Sef and MAP Kinase phosphatase 3 (MKP3) which modulate particularly the Ras/Erk pathway at different levels (Mason, 2007). In contrast, stimulation of the fibronectin leucine-rich transmembrane type III (XFLRT3) protein causes FGF signalling to be positively regulated (Bà ¶ttcher et al., 2003). Sprouty (Spry) was one of the first identified feedback regulators of the FGF pathway. Thisse and Thisse (2005) found Spry to antagonise FGF Signalling by gain and/or loss of function experiments in mouse. Spry acts at the level of Raf and/or Grb2 (Fig. 4). Gain and/or loss of function experiments in zebrafish demonstrated that Sef antagonises FGF signalling (Fig. 4) acting at level of MEK and ERK (Tsang et al., 2002). Mouse studies have suggested that FGFR signalling is required for Dusp6 transcription which codes for MKP3 (Ekerot et al., 2008). From this study it was also found that MKP3 acts as a negative regulator of ERK activity (as seen in Fig. 4). Sef and XFLRT3 are located at the membrane (Fig. 4) and carry out antagonising actions with FGFR directly. FGF signalling can be regulated at different levels, from the membrane all the way down to the level of phosphorylation of MAPK and it is important also to know that FGFs have been detected in the nucleus (Mason, 2007). Most of the downstream target genes as described earlier are feedback inhibitors (Spry, Sef and MKP3) but FGF signals are also known to interact with many other important pathways such as transforming growth factor-ÃŽ ² (TGF-ÃŽ ²), Hedgehog (HH), Notch and Wnt (Gerhart, 1999). Therefore, in conjunction with these, FGFs are responsible for development of most organs of the vertebrate body. In the nervous system, FGFs have been implicated to play a role in early developmental processes, such as neural induction, patterning and proliferation (Umemori, 2009). Neural induction: The Default Model Spemann and Mangold (1924) pioneered the study of neural induction, which is defined as the process by which naive ectodermal cells aquire a neural fate. Their work involved demonstrating that tissue from the dorsal lip of the frog Xenopus laevis blastopore could induce a second ectopic nervous system (Fig. 5 above left) when implanted onto the ventral side of a host gastrula embryo. The second ectopic nervous system was host derived indicating that the graft was important in determining cell fate. This region, located on the dorsal side of an amphibian embryo, was named the Spemann organizer as it could direct the neighbouring ectodermal cells to form nervous system instead of epidermis. Although the organizer (group of dorsal mesodermal cells) was found to be present in many species (Hamburger, 1988) it was the Xenopus laevis which gave an insight into the molecular events involved in neural induction in vertebrates (Hemmati-Brivanlou et al., 1994). This was particularly because amphibians were found to be ideal experimental models for the study of neural induction as neurulation initiated within twelve hours after fertilisation (Weinstein and Hemmati-Brivanlou, 1997). It was implied that signals from the organizer provide instructions to the ectoderm to form neural tissue therefore for many decades the view was that the default state of the ectoderm was to produce epidermis. The first challenges to this model came from studies making use of dissociated cell cultures (Sato and Sargent, 1989). It was found that when animal caps were cultured intact that epidermis formed but neural tissue arose from animal caps that had been dissociated for prolonged periods (as seen in Fig. 6 below). This led to the idea that intact tissue may block the formation of neural tissue by presence of neural inhibitors which are diluted out when the tissue is dissociated. Recent research has found that the default nature of the ectoderm is to produce neural tissue that requires inhibition of a neural inhibitor from the ectoderm. Before considering the process of neural induction I would like to take a step back and describe the three germ layers of the embryo. Following fertilisation, the zygote undergoes stages of cleavage to eventually form a gastrula with three germ layers (in triploblastic animals) usually only visible in vertebrate animals. The Germ layers will eventually give rise to all of the animals organs through a process known as organogenesis. The three layers include, the ectoderm (outermost), endoderm (innermost) and mesoderm (which is between the ectoderm and endoderm) layers. The Endoderm gives rise to the lung, thyroid and pancreas. The mesoderm forms the skeleton, skeletal muscle, the urogenital system, heart and blood. The outermost layer, the ectoderm which is of concern here, gives rise to the epidermis and nervous system. It is at gastrulation that the vertebrate ectoderm is competent to differentiate into neural tissue or epidermis. Unless told otherwise, the default nature of the ect oderm is to produce neural tissue and this was outlined as the default model. The Default model of vertebrate neural induction, discovered over a decade ago in Xenopus, proposed that in the presence of bone morphogenetic protein (BMP), a signalling molecule of the TGF-ÃŽ ² superfamily, causes the ectoderm to give rise to an epidermal cell fate (Stern, 2006; Muà ±oz-Sanjuan and Brivanlou, 2002). In support of this model, consistent with the idea that BMP activity inhibits neural fates, animal caps which had been injected with RNA encoding effectors of BMP4 (Smad 1/5 or Msx1) neuralization did not occur. Conversely, it was found that inhibition of BMP activity in the ectoderm is essential for a neural fate which forms the basis of the default model of neural induction. Inhibition of BMP is achieved through direct binding of BMP antagonists emitted from the organizer (Wilson and Hemmati-Brivanlou, 1997). These BMP antagonists include chordin (Sasai et al., 1995), noggin (Lamb et al., 1993) and follistatin (Hemmati-Brivanlou et al., 1994) which bind to BMPs extra cellularly to prevent its interaction with its own receptor (Hemmati-Brivanlou and Melton, 1997). These molecules have direct neural activity which means they induce formation of neural tissue in the ectoderm without forming mesoderm. It was initially believed that these molecules acted as ligands to bring about neural tissue formation. Experiments found that there was conservation through species, identifying that chordin was homologous to the short gastrulation (sog) gene found in Drosophila which has been shown to antagonize the BMP homologue decapentaplegic (dpp) (Wharton et al., 1993), suggesting that these molecules might act as inhibitors rather than inducers and that these inhibitory mechanisms have been conserved from arthropods through to vertebrates. It was experiments (Fig. 6) showing that dissociated ectodermal explants would become neural tissue in absence of inducing signals from the organizer (Sato and Sargent, 1989). Evidence found that neural induction resulted from inhibition of the TGF-ÃŽ ² pathway as expression of dominant-negative activin receptor gave rise to neural fates in amphibian ectoderms (Hemmati-Brivanlou and Melton, 1994). It was found that chordin, noggin, follistatin and molecules such as Cerberus and Xnr3 (Xenopus nodal related 3) bound to BMP in the extracellular space inhibiting its action (Hemmati-Brivanlou and Melton, 1997) leading to the much debated default model of neural induction. Neural Induction: FGFs get it started Support for the default model still remains, mainly in Xenopus, but other work (especially in chick and mouse) suggests a more complex mechanism (Streit et al., 1998). It has been established that the BMP pathway is involved in determining ectodermal cell fate (Wilson and Hemmati-Brivanlou, 1997) but it still remains to be proved conclusive if BMP inhibition is required for neural induction alone or if other pathways act separately or with BMP inhibition. In the chick embryo it has been found that naive epiblast cells do not respond to BMP antagonists until previous exposure to organizer signals for five hours (Streit et al., 1998). Striet et al. (2000) grafted an organizer to observe the genes induced in the epiblast within this time period. A gene ERNI (early response to neural induction) was identified as a coiled coil domain with a tyrosine phosphorylation site and found to be expressed throughout the region that later contributes to the nervous system at pre-primitive streak stages (Hatada and Stern, 1994). Striet et al. (2000) findings made ERNI the earliest known marker after a response to organizer signals, prior to even Sox3 (induced by the node in 3 hours (Streit and Stern, 1999)). FGFs are becoming more evident that they have a major role in neural induction as it has been shown to begin before gastrulation, before BMP antagonists even appear (Wilson et al., 2000). In the chick, it has been found that FGFs have the role of blocking BMP signalling and promoting neural differentiation (Wilson et al., 2000). In ascidians, FGF signalling is the main mechanism of neural induction with BMP antagonism playing a role in later development (Lemaire et al., 2002). In frogs and fish, in contrast, FGFs do not have a certain role in neural induction and is believed their primary role is BMP inhibition (Pera et al., 2003). Exposure of the chick epiblast to an implanted organiser for around 5 hours induces Sox3 (an early neural plate marker) (Stern, 2005). After removal of the implanted organiser, chordin can be used to stabilise it (Striet et al., 1998) which implies that before the ectoderm can respond to BMP antagonists it must be exposed to 5 hours of signals from the organizer. During these 5 hours, several genes become activated such as, ERNI (early response to neural induction) which becomes active after 1 hour (Streit et al., 2000) and Churchill (Chch) after about 4 hours (Sheng et al., 2003). These are both induced by FGF and not BMP inhibition, indicating the importance of FGFs in early neural induction. Churchill which is expressed in the neural plate inhibits brachyury, a transcription factor, which as a result suppresses mesoderm formation by preventing cell ingression. In the chick, FGF8 is expressed in the hypoblast, prior to gastrulation before Hensens node appears (the chick equivalent to the organizer) indicating that neural induction is in fact able to begin before gastrulation. This is important because ERNI and Sox3 mark neural induction and require FGF signalling (Stern, 2005). Streit et al. (2000) found that FGF8 coated beads induce ERNI as efficiently as the node within 1-2 h without inducing brachury and also the expression of Sox3. These results indicate FGFs to be possible early signals in neural induction. It is FGF8 which has been identified as the best candidate because it is expressed in the anterior part of the str

Life, Death, and Frankenstein Essay -- Frankenstein Essays

Life, Death, and Frankenstein Since I spent last weekend in Vancouver attending the funeral of a beloved aunt who died on Good Friday, you could say that I've been pondering a lot about death and dying lately. It didn't help either that I chose to bring my copy of Mary Shelley's Frankenstein with me to read on the plane rides there and back, seeing as this story deals with the creation of a new form of life and the deaths that result from it. Being in this rather morbid frame of mind, I decided for this commentary just to take a closer examination of life and death as contained within the kind of gothic narrative of this early science-fiction horror story. It's almost like a Yin-Yang pairing between the two: Victor controls the ability to create Life (an ability that is usually looked on as being feminine) through his scientific and medical knowledge, and the Creature controls the ability to create Death (an ability usually looked on as being masculine) through his incredible strength and physical abilities. But although the Yin-Yang of Taoist thought brings harmony to the universe, this pairing of light and dark brings nothing but destruction to those it touches. So, in Frankenstein, I suppose you could divide the death into two different categories, both centered around Victor: Life from Death, and Death from Life. "To examine the causes of life," Victor tells us through Captain Walton, "we must first have recourse to death." And so he does. After Victor discovers the secret to creating life (what it is we are never told, but if you're inclined to believe the various cinematic treatments of the story, it seems to involve lightening storms and complicated machines), he decides to put this to use and see if he can play... ...ankenberry Cereal available for sale, with cartoonish pictures of Boris Karloff smiling on the front. While they may hold opposing powers of Life and Death respectively, in the end, it is as though neither of these two characters is left with any life between them. Everyone Victor has loved is dead because of the attacks inflicted by his creation. The Creature is not accepted by society because of the appearance given to him by his creator. Neither of them having anything left to live for; they engage in a chase up to the high Arctic where the Creature and the body of his creator disappear into the night. With each of them trying to out-manoeuvre the other, each destroys what his opposite desires the most. In this Life from Death, nothing can lead a true existence. Works Cited: Shelley, Mary. Frankenstein (1818 ed.). New York: W. W. Norton & Company, 1996.

Kants Moral Principles Essay -- Kant Immanuel Philosophy Morals Essay

Kant's Moral Principles   Ã‚  Ã‚  Ã‚  Ã‚  In the Foundation of the Metaphysics of Morals, the author, Immanuel Kant, tries to form a base by rejecting all ethical theories that are connected to consequences, and then focusing on our ethical motivations and actions. Kant wants to derive good characters out of contingently right actions. He believes that everything is contingent (everything can have good or bad worth, depending on how it is used). So he is trying to find the supreme principal of morality in all his reasoning. Kant also believes that an action is right or wrong based solely on the reason by which it was performed. However, a Utilitarian, like John Mill, would reject Kant’s reasoning of originating good characters out of actions alone, and instead argue that if an action has bad consequences, then the action was morally wrong.   Ã‚  Ã‚  Ã‚  Ã‚  Kant believes that an action has moral worth only if it is done out of respect for our moral code. He names this moral action a ‘duty.’ Kant also believes that in determining the moral worth of an action, we need to look at the maxim by which it was performed. So, we need to look at one’s reason for doing an action to determine if it is a duty. If the reason for performing the action is justified, then the action is a duty. However, Kant says there are two different types of reasons for performing an action. Kant calls these reasons ‘imperatives.’ The first reason for performing an action, the hypothetical imperative, is based on consequences and on our personal preferences. They are also contingent, meaning that they can be good or bad depending on how they are used. People choose to perform a given action because of the hypothetical imperative. The second reason for performing an action according to Kant is called the categorical imperative. These are not based on our preferences, don’t deal with consequences of an action, and are derived a priori. They are completely separate from hypothetical imperatives. We all have knowledge of categorical imperatives before experiencing them first. They are kind of a second nature for us, which needs to be recognized according to Kant. These are the most important reason for performing an action. These imperatives also have the characteristics that Kant needs in order to make his point that all of our moral principals are categ orical, have absolute authority, and are independent o... ...t hope to predict the outcome of any given situation. It is impossible; there is no such thing as seeing the future. So by making a false promise to your friend, you have still done the morally wrong action, even though it will most likely save them some suffering. It did indeed take away their choices, so they can’t act in a way they want to act (going to class). I happen to agree with Kant’s idea here. I think that no matter what the consequences are, performing the right action is always the right thing to do.   Ã‚  Ã‚  Ã‚  Ã‚  Overall I think that Kant has better arguments because they are directed at the individual, not at society in whole. I also agree that the moral worth of actions is determined by the motivating principal of the action, not by the consequences, like John Mill. So I am a deontologist, for the most part. However, I also agree with some of the things that Mill has to say. So is there a way that we can combine the ideas of Mill and Kant together in order to form a perfect society in which everybody is happy? I don’t know the answer to this question, but we should all strive to do so, and we should start by respecting each other’s autonomy and treating others as ends.

Superconductivity and Superconductors :: Physics Physical Essays

Superconductivity and Superconductors ABSTRACT Superconductivity allows current to pass through a material with no resistive losses at near absolute zero temperatures. It also exhibits the Meissner effect which causes the superconducting material to repel magnetic fields. The application of this technology has been extremely limited due to the prohibitive costs of using Helium to cool the material to the critical temperatures. Recently, however, new ceramic materials were discovered which exhibit superconductive properties at higher temperatures which can be reached using cheaper liquid Nitrogen cooling. Applications have immediately expanded and are expected to become amazing in the near future as scientists search for a room temperature superconductor. ORIGINS Superconductivity is the passing of electricity through conductors with no loss of power (Graham 17).

Rousseau and Wollstonecraft

â€Å"The neglected education of my fellow-creatures is the grand source of the misery I deplore. â€Å"-Mary Wollstonecraft, A Vindication of the Rights of Women. Rousseau and Wollstonecraft believed that children should be allowed to grow freely and learn to use their education practically. Children would then grow up to be free thinking adults that would keep soceity from becoming materialistic and oppressing. Nonetheless, they vehemently disagreed on who should receive such an education. Rousseau thought that only males, because they are stronger should receive such and education. Wollstonecraft believed everyone, no matter what sex, should be able to be educated to reform and better society as a whole. Though both their works were considered extreme, they are both apparent in the public education system of today. Wollstonecraft (1759-1797) and Rousseau (1712-1778) both agreed that society oppressed human kind, but Wollstonecraft felt that men were oppressing women. They both believed that education should mean letting children grow freely and placing little restrictions. They should protect them from immediate dangers and provide food and shelter. They should not, however, force books and controlled learning upon the children. He thought that children should also develop common sense and each child would choose whatever interests him to study in greater detail. He thought that this method of education would produce a well balanced, free thinking child. Therefore this would lead to a natural society rather than a materialistic one. Rousseau†s theory of natural education was not intended for all children. He felt that girls should be limited motherhood, and how to be a wife. To Rousseau, women exist in order to serve man, because they are weaker. Wollstonecraft stated that women should be taught medicine in order to take care of parents, infants, and husbands properly. She endorsed equal education for all children no matter what the sex. They should not only be taught the same things, but should be taught together, to learn social interaction they would encounter as adults. Girls and boys would attend day school together and then boys would be sent to their apprenticeships and girls would learn how to sew and other skills. Wollstonecraft tried to prove that by denying a woman†s education you are denying her the ability to raise children adequately. Therefore it would benefit both sexes if women were properly educated. Rousseau was applauded for advocating human rights and natural education but when it concerned women he broke no new ground. He actually promoted women†s role as a wife and mother present to serve her husband. He stated that because women were weaker physically that their minds were as well. Wollstonecraft upheld his philosophy of natural education to encourage individual freedom to benefit society. However, she detested his treatment of women. She advised that women and men should both be educated, and educated together. Both of Emile and The Vindication of the Right†s of Women were considered radical, they were both revolutionaries. Emile impacted practical applications, and the exploration of natural curiosity in education. Wollstonecraft†s radical idea of educating boys and girls equally, and together are applied on public education today.

European and Asian continents Essay

The author Jared Diamond in the book Guns, Germs and Steel: The Fates of Human Societies writes that the alternative title for his book would probably be a short history about everyone for the last 13,000 years. This topic will explain the author’s main argument as well as cite a passage where he states his points clearly. We will also give two proximate and two ultimate factors to support his claims, ending with an evaluation of his main argument. It should be noted that the main argument the author brings forward in this book has been mentioned quite well in the preface the rest of the book merely acts as a supplement to his main idea. The main argument in this book is summed up clearly in the following question: â€Å"Why did wealth and power become distributed as they now are, rather than in some other way? For instance, why weren’t Native Americans, Africans, and Aboriginal Australians the ones who decimated, subjugated, or exterminated Europeans and Asians? † (Diamond p. 13-32,1999) He explains this by saying that the advancements in culture in the European and Asian continents are not due to their moral, intellectual or genetic superiority. Rather the gaps in development are mostly due to the geographical advantages each race had. He says that the earliest civilizations were hunter-gatherers before they eventually developed a system of agriculture. This of course leads to the production of food surpluses such supports larger populations and in effect a larger population necessitates a division of labor. This leads to large societies with ruling classes and supporting classes which in turn becomes a ruling organization. He explains two Ultimate factors which lead civilizations down this path, a large east/west axis and easily domestic able food and animals. â€Å"There were also great differences in the completeness with which suites of crops and livestock spread, again implying stronger or weaker barriers to their spreading† (Diamond p. 176-192, 1999). He says that the early advantages of finding suitable plants to grow and domesticated animals helped certain cultures advance further than others. Genetically geographical areas decide whether certain crops will be wild or domesticated. It also decides the animals that will inhabit the area. â€Å"Most of the wild species from which our crops were derived vary genetically from area to area, because alternative mutations had become established among; wild ancestral populations of different areas†. (Diamond pg 176-192, 1999) For example the Middle East had the best collection of plants and animals suitable for domestication. And as they began to trade they found the importance of using horses and donkeys as transport. In contrast in Africa they had to contend with growing wild plants such as sorghum and yams. Animals such as zebras could not be domesticated and those animals which flourished in one area could not survive in the other. â€Å"South Africa’s Mediterranean climate would have been ideal for them, but the 2,000 miles of tropical conditions between Ethiopia and South Africa posed an insuperable barrier†. (Diamond pg 176-192, 1999) He also says that the east-west axis is certain countries were essential to the advancements of their societies through trade. While the north-south axis of certain countries such as Africa promoted slow diffusion. The title of this book sums up the two proximate factors that lead to the dominance of the Eurasian races and the displacement and subjugation of the Africans, Native Americans and Aborigines. In terms of germs the Eurasians increasing levels of trade and use of livestock increased the number of pathogens they were exposed to forcing immunity among their populace. When they met the indigenous tribes of South America these diseases dwindled their populations to a point where the Europeans could subjugate them. â€Å"As a result, over the course of history, human populations repeatedly exposed to a particular pathogen have come to consist of a higher proportion of individuals with those genes for resistance–just because unfortunate individuals without the genes were less likely to survive to pass their genes on to babies† (Diamond p. 195-214, 1999). The technological progress of these people also depended on food production. The increasing organizational systems and trade with other areas provided them with the tools to develop a writing system of their own. This writing system was essential to the continued technological development of societies. â€Å"Here we have to remind ourselves that the vast majority of societies with writing acquired it by borrowing it from neighbors or by being inspired by them to develop it, rather than by independently inventing it themselves† (Diamond p. 215-238, 1999). After reading this book I found myself agreeing with many of the author’s contentions about our history. It is difficult to conceive that the history of human civilization was decided even before it births. However the argument the author provides not only for the agricultural advancements but also in terms of geopolitical advancements seem as true as they are simple to understand. If I had to point out one fault it would be that the author speaks of competing civilizations in terms of continents rather than individual societies. It is unreasonable to me that all the societies on a continent would follow a singular goal of increasing their footprint upon the earth. Additionally he does not adequately expand his theory to include the society of ancient Egypt, which despite its geographical commonality through several decades managed to go through several periods of dominance and subjugation. However, the book itself is an essential read when taken as a viable theory of the history of human civilization. References Diamond, J. M. (1999). Guns, Germs, and Steel: The Fates of Human Societies. New York: W. W. Norton & Co.

Acute Care: Care Implementation and Evaluation.

Acute Care: Care Implementation and Evaluation. This assignment will be based around the care that is implemented and evaluated, within a National Health Service (NHS) Foundation Trust (FT). The focus of the assignment will be to discuss two health problems that a selected patient has and has been admitted to the FT with. The selected patient had been admitted into FT with breathing difficulties and also suffering from dehydration. The assignment will focus upon the goals that are set for the patient whilst in FT and the reasons why the goals are set. The patho-physiology of the two problems will also be discussed and also the care that had been implemented to achieve the goals. Throughout the assignment, the patient will be known as Terry with the permission from the patients parents, according to the Nursing and Midwifery Council (NMC, 2008) confidentiality guidelines. The assignment will also aim to discuss the role of the Health Care Professional (HCP) in planning appropriate care for the patient, in particular, using the assessment technique of goal setting by using Specific, Measurable, Achievable, Realistic and Time Set (S. M. A. R. T) target planning technique (Roper et al, 1996). The reasons for planning care can involve the HCP assisting in preventing potential health problems, for example, breathing difficulties for the patient becoming worse and to also assist in solving problems where possible. Care planning can also assist in alleviating possible health problems that cannot be solved by HCP’ s and so will need the assistance of Multi Disciplinary Team (MDT) , for example, consultant, physiotherapists to further improve an develop the care plan. Terry is a 42 year old single man, who lives with his parents, and has suffered from a number of illnesses throughout his life, for example, optical glyoma, Deep Vein Thrombosis (DVT), epilepsy, and also learning difficulties. Terry has difficulty with breathing, and this appears to have been caused by respiratory rhythmicity centre in the medulla and the pons (areas of the brain which can control breathing) and these appeared to not be working in the correct way (MacKenzie, 1996; Waugh et al 2006). Terry’s reduced neurological status was due to trauma that had been suffered in the motor pathways, and the peripheral nerves, in the brain (Iggulden, 2006). Terry was admitted to the Intensive Care Unit (ICU), within the NHS FT, suffering from numerous problems that were mainly neurological. Terry's admission to ICU was due to the increased breathing difficulties that he was experiencing. Due to the breathing difficulties, the nursing team, and Terry's consultant, agreed that it would be best for Terry to have a percutaneous tracheostomy inserted. Due to Terry suffering from a probable cerebellar lesion, severe learning difficulties and poor communication skills; it did appear that Terry could not understand what the nursing team were informing him of, the medication that he needed and the care that was being delivered (NMC, 2008). Due to the fact that Terry appeared not to be able to understand or communicate with the nursing team, and that his parents and family members were with him, the nursing team, and myself, ensured that the parents, and family members, were informed of what was happening regarding the care that had given to Terry. The fact that Terry could not understand the instructions given to him, due to learning difficulties, consent to insert a percutaneous tracheostomy had to be given from Terry’s parents, to the Consultant (NMC, 2008). The tracheostomy that had been inserted into Terry helped the nursing team in the ICU and on the ward, to oxygenate Terry to the optimum level of 98%. The tracheostomy, also ensured that Terry was able to maintain a breathing rate of between 35 and 50 breathes per minute (Bailey, 2008). Although Terry was able to maintain a respiration rate, the normal respiration rate for an adult is normally between 14 and 18 breathes per minute (Bailey, 2008). The nursing care that had been implemented included ensuring that oxygen was flowing through the tracheostomy and this ensured that Terry had enough oxygen in his body for his heart and lungs to function, and that the heart pumped the oxygenated blood around the body (Machin et al 1996; Roper et al, 1996; Bailey et al 2008). Due to Terry’s respiration centre not working properly, and suffering from breathing problems, this meant that gaseous exchange was impaired, and led to a risk of respiratory acidosis. Gaseous exchange is where the oxygen goes into the alveoli capillaries, and the carbon dioxide is moved out of these capillaries (Bailey, 2008). The respiration centre is made up of a group of nerve cells, which are in the reticular endothelial system of the medulla oblongata. These cells send impulses to the motor neurones, via the spinal cord, and are then sent to the intercostal muscles (Bailey, 2008). The trauma that Terry had suffered with, was a possible cerebella lesion when he was a child. When Terry was admitted, his oxygen level was 82% (Bailey, 2008). The goal for this problem was to keep Terry's respiration and oxygenation at a level that was suitable. A suitable level of respiration for an adult is between 14 and 18 breaths per minute, and an oxygen level of around 97 to 98% (Bailey, 2008). The patho-physiology of breathing difficulties includes a lack of oxygen to the tissues of the body, including the brain, and even death (MacKenzie, 1996; Waugh et al 2006). Due to Terry haiving an oxygen saturation level of 82%, we set the goal that we would aim for and set this goal with his parents. The goal that the nurses had set with Terry's parents, due to the fact that Terry had learning difficulties and could not set the goal with the nurses. The goal was set as the nurses aimed to have his oxygen saturation level between 95% and 98% within two hours. The goal had to fit in with the Specific, Measurable, Achievable, Realistic and Time Set (S. M. A. R. T) target planning technique (Roper et al, 1996; Faulkner, 2000). Terry's sitting and lying position had to be carefully planned around him, this ensured that we as a nursing team where able to ensure that his lungs would expand to their optimum and to maintain a satisfactory oxygen saturation levels within his body (Roper et al 1996; Machin et al 1996; Hackman, 2008). The normal oxygen saturation level is between 95% and 98% (Woodrow, 1999). The fact that Terry had an oxygen saturation level of just 82%, the Consultant had to prescribe oxygen for Terry. The oxygen that had been prescribed for Terry, had been increased from 24% to 40% (NMC, 2002). The consultant advised us to ensure that the oxygen was to be humidified. Due to Terry having the tracheostomy, we were able to deliver the oxygen with the use of a tracheostomy mask and what is called a T-piece circuit (Machin et al 1996; Dolan, 2008; Soady, 2008). The consultant also advised the nursing team to ensure that neurological observation's were undertaken, especially the oxygen saturation levels, every 15 minutes until Terry's oxygen saturation levels had risen to 96% (Machin et al 1996; Dolan, 2008; Soady, 2008) The neurological observations with regards to the goal, meant that the nurses were able to deliver oxygen, which would enable the oxygen saturation level to be maintained (Machin et al 1996; Dolan, 2008; Soady, 2008). Once the nursing team had ensured that the oxygen had been delivered to Terry at 40% and was humidified, they then ensured that 15 minute observations were maintained. The Consultant had to ensure that the 40% oxygen that he had verbally prescribed, was documented and written clearly in Terry's medical notes and on his prescription sheet (NMC, 2002; NMC, 2004). The fact that Terry had been prescribed the higher rate of oxygen, this needed to be clearly documented within Terry’s nursing notes (NMC, 2004). The documentation was needed, so that the other nurses were aware of the change. Although the observations had been maintained every 15 minutes, with regards to Terry's oxygen saturation levels, this ensured that the nursing team maintained Terry's neurological observation's (Machin et al 1996; Dolan, 2008; Soady, 2008). The goal that had been set by the nursing team and Terry's parent's, for his oxygenation levels did fit into the Specific, Measurable, Achievable, Realistic and Time Set (S. M. A. R. T) target planning technique. The goal was specific, measurable and realistic for Terry and the nursing team caring for him, as well as being achievable in the time frame that had been set by Terry's Consultant (Faulkner, 2000). Due to the fact that the nursing team had achieved this goal for Terry, proved that the nursing care and interventions made by the nursing team, were effective. The nursing care and interventions were effective enough, for this goal to have been met (Roper et al 1996). The goal that had been set for Terry with regards to his oxygen saturation level, had to be documented. The goal had to be documented within the nursing notes, which the nursing team had to document clearly. The nursing team were able to hand over the information about Terry, to the nursing staff that would have been caring for him on the next shift. (NMC, 2004) The second of Terry's problem's is that he was at risk of dehydration, this was due to the fact that Terry could not swallow as he had a reduced neurological status. The fact that Terry could not swallow was due to the motor area of cerebral cortex of his brain, did not work in the way that it should (Waugh et al 2006). The motor area of the cerebral cortex of Terry's brain, was damaged due to the increase in epileptic seizures. Dehydration can cause the cells to deplete, due to not having enough fluids for them to replenish. The cells replenish in the sense that the fluids help the cells to regenerate, regulate the body temperature, to dilute the waste products within the body, and to maintain the level of fluids within the tissue fluid and blood (Waugh et al 2006). The patho-physiology of dehydration includes thirst, the mouth being dry, the tongue would look leathery, and fluid from within the tissues and skin would be withdrawn (Roper et al 1996; Brown, 1997; Day, 1997). Due to Terry not being able to drink fluids, he was not able to regulate his own body temperature, nor was his body able to dilute the poisonous substances in his body (Waugh et al 2006). Due to fluid being withdrawn from the body, this would mean that the body would not be able to maintain its own volume in blood (Roper et al 1996). The patho-physiology of not having enough fluids also includes the kidneys would excrete less than they normally would; a person would be lethargic; the skin would lose its elasticity and would appear to be more wrinkled (Roper et al 1996; Brown, 1997; Day, 1997). If Terry had been suffering from dehydration, his would have looked sunken and his urine output would be reduced as well as being more concentrated. If Terry had been suffering from a severe case of dehydration, his blood volume would be reduced. If the blood volume was to cause a circulation deficiency, this would cause his kidneys to fail to excrete the waste products that they normally excrete (Roper et al 1996; Brown, 1997; Day, 1997). Due to Terry not drinking the recommended two litres of fluids per day, we had to set a goal. The goal that had to be set, had to be set with Terry's parents (Roper et al 1996). The goal for the second problem, was to prevent dehydration during Terry's stay in hospital, through ensuring that Intravenous Saline was delivered through venous access (Dougherty et al 2008). The Intravenous Saline had to be delivered through venous access, due to the fact that this was the most effective way in which to infuse fluids. The fluids had to be infused over a period of 24 hours, due to the volume of the fluids. The Consultant prescribed two litres of Intravenous Saline, and the nursing team ensured that it was delivered (NMC, 2002; NMC, 2004; Dougherty et al 2008). Due to the fact that the fluids needed to be infused, the nursing team ensured that the fluids were delivered through the venous access, by using an infusion pump. The pump that was used by the nursing team, was the volumetric pump. The volumetric pumps allow health care professionals to administer large amounts of infusions, and this is why were used this type of pump to deliver the fluids that Terry needed over a 24 hour period (Sarpal, 2008). Due to the fact that the nursing team were delivering Intravenous Saline to Terry, it was important that this was documented by the nursing team within his nursing notes. The fact that this was documented in Terry's notes, ensured that the information was handed over to the nursing team on the next shift (NMC, 2004). It was important hat a fluid balance chart was also documented, as this would help the nursing team to ensure that the amount of input from fluids, was similar to Terry's urine output. The fact that the nursing team were able to monitor Terry's fluid input and output, ensured that his body was not retaining any of those fluids within a 24 hour period (Hunt et al 2008). The goal for dehydrat ion by providing two litres of Intravenous Saline over a 24 hour period, did fit into the Specific, Measurable, Achievable, Realistic and Time Set (S. M. A. R. T) target planning technique. This was due to the fact that the goal was specific, measurable and time set. The goal was achievable and realistic, but only while Terry's venous access was as good as it was. When Terry's venous access for the Intravenous Saline to be delivered was poor, this meant that the nursing team had to find another route to deliver these fluids. The nursing team had to re-set the goal for delivering the Intravenous Saline. (Faulkner, 2000) Due to the fact that the nursing team could not deliver the Intravenous Saline through the venous route, had to be documented. The nursing team had to document the fact that Terry had poor venous access, and that they had asked his Consultant to review Terry (NMC, 2004). When Terry's Consultant had been to review him, the Consultant advised the nursing team to deliver the Saline through Terry's PEG tube. Terry's Consultant had to document the fact, that he had advised the nursing team to deliver the Saline through Terry's PEG tube. The Consultant also had to document that his advice was due to Terry's poor venous access in Terry's medical notes, and he had to document this on the prescription chart (NMC, 2004). Due to Terry having a Percutaneous Endoscopic Gastrostomy (PEG), the nursing team and Terry's parents re-set the goal to deliver the fluids that Terry needed (Faulkner, 2000). The new goal that had been set, was to deliver one litre of Intravenous Saline through Terry's PEG tube. The litre of Saline was delivered to Terry through his PEG tube, over an 8 hour period rather than a 24 hour period. Even though the nursing team had to deliver the fluids through the PEG tube, they had to ensure that the goal did fit into the Specific, Measurable, Achievable, Realistic and Time Set (S. M. A. R. T. ) target planning technique. This goal was specific, measurable, achievable, realistic and time set for Terry and the nursing team (Faulkner, 2000). Before the nursing team could deliver the Saline through Terry's Percutaneous Endoscopic Gastrostomy, the Saline had to be prescribed by his Consultant. The Consultant had to document the Saline on Terry's prescription chart, and also had to document the route that the nursing team were to deliver the Saline (NMC, 2004). The Saline that had been prescribed by Terry's Consultant, also had to document in Terry's medical notes, that he had prescribed this and also document the route that he had advised to the nursing team (NMC, 2002; NMC, 2004). When the nursing staff had commenced the delivery of the Saline through the Percutaneous Endoscopic Gastrostomy (PEG) tube, they themselves had to document this. The nursing team had to document the Saline running through the PEG tube, to enable the nursing notes for Terry to be up-to-date. The nursing team to document the amount of Saline that was to run through Terry's PEG tube, and what time the Saline infusion began. The nursing team also had to document how much of the Saline was to be infused in any one hour, when the Saline was due to finish, as well as document the lot number and expiry date that were on the bag of Saline. NMC, 2002; NMC, 2004) The documentation of the infusion of the Saline running through Terry's Percutaneous Endoscopic Gastrostomy (PEG) tube, ensured that the nursing team could hand over the information to the nursing team that were due to care for Terry on the next shift (NMC, 2004). The goal that had been re-set by the nursing team, and Terry's parents, fitted in with the Specific, Measurable, Achievable, Realistic and Time Set (S. M. A. R. T. ) target planning technique (Faulkner, 2000). The fact that the goal had to be re-set, ensured that the nursing team had been able to deliver the Saline through the Percutaneous Endoscopic Grastrostomy (PEG) tube. The goal to deliver the Saline through the PEG tube, had been specific, measurable, realistic and time set for Terry and the nursing team. This goal had been achieved, due to the fact that the care that the nursing team had been able to deliver the Saline in the time that they had set with Terry's parents (Faulkner, 2000). Due to the goal being achieved in the time frame that had been set by the nursing team, and Terry's parents, meant that the nursing team had been able to deliver the care that had been needed to achieve this goal (Faulkner, 2000). I am now at the point in this assignment when I can reflect. For my reflection, I will be using the Gibb's Reflective Cycle to reflect upon this assignment, which is documented within his book that was published in 1988 and entitled Learning by Doing: A Guide To Teaching and Learning Methods (Gibb's, 1998). Due to the fact that Terry ad a number of health problems, I had a hard task of choosing which two that I would use. I did have to think long and hard about which two health problems that I would use, but I was given permission from his parents to enable me to write this assignment (NMC, 2008). The two health problems that I had chosen, were breathing difficulties and dehydration. Due to the breathing difficulties that Terry suffered with, meant that his oxygen saturation levels were low. Due to Terry's breathing difficulties, this is why the nursing team, and his Consultant, had to gain consent from Terry's parents, to insert a percutaneous tracheostomy. The fact that the tracheostomy was inserted soon after Terry's admission, enabled the nursing staff within the ITU and the ward of the NHS FT, to ensure that Terry's oxygen saturation levels were maintained. Therefore, this is the reason why a goal was set. Due to a goal being set for Terry's oxygen saturation levels to be maintained, provides evidence to show that the nursing interventions were effective. The effectiveness of these nursing interventions, proves that goals that are set for an individual patient can also be met. The second goal that had been set for Terry by the nursing team, and his parents, had fitted in with the Specific, Measurable, Achievable, Realistic and Time Set (S. M. A. R. T. ) target planning technique. Due to the fact that this goal was only partially met, did not necessarily mean that the care that had been delivered to Terry, had been ineffective. The care that had been delivered to Terry had been effective, but the goal could no longer be achieved through the venous route, due to the fact that Terry's venous access was poor. Due to Terry's poor venous access, this is why the nursing team had to re-set the goal with his parents. The goal that had to be re-set, fitted in with the Specific, Measurable, Achievable, Realistic and Time Set (S. M. A. R. T. ) target planning technique. The goal had been re-set, and had also been achieved in the time frame that had been set with Terry's parents. The goal that had been re-set, had been achieved in the time frame that had been set. The goal had been achieved due to the fact that, the nursing team were able to deliver the Intravenous Saline through the Percutaneous Endoscopic Gastrostomy (PEG) that Terry had in place. The fact that the nursing team could not achieve this goal when it had first been set, was not an issue that could have been anticipated. Even though nursing teams can not anticipate why the goals are not met, they can re-set the goal and in time, meet the new goal. Therefore, the nursing care and interventions that are delivered, do make nursing care effective. Documentation of all care from the nursing team was important, due to the fact that the nursing team on one shift, were able to inform the nursing team of the next shift. Documentation also ensures that if the nursing team were unsure of any test results, that they were able to look over the nursing notes to ensure they knew where we were up to with the patient. 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