Frizzled Family Essay

The idea of family is a central theme in Lorraine Hansberry’s play A Raisin in the Sun. Hansberry alludes to the Old Testament book of Ruth in her play to magnify “the value of having a home and family”(Ardolino 181). The Younger family faces hardships that in the moment seem to tear them apart from one another, but through everything, they stick together. The importance of family is amplified by the choices of Walter and Beneatha because they appear to initiate fatal cracks in the Younger family’s foundation, but Mama is the cement who encourages her family to pull together as one unit. The hardships of the family help develop a sense of unity for the Younger household.

The CFTR gene encodes a protein that is present in epithelial tissues in lungs, sweat glands, and pancreas, and helps

ICG 001 is a Wnt/β-catenin pathway inhibitor. Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia is a kind of ravaging condition of progressive lung scarring and destruction. Anti-inflammatory therapies such as corticosteroids have limited efficacy in ultimately fatal disorder. Because aberrant activation of theWnt/β-catenin signaling cascade occurs in lungs of patients with IPF.

Cystic Fibrosis is the result of a genetic mutation in the CFTR gene on chromosome 7. This disease is more common to the Northern European population, with over 1500 different mutations that can occur on this gene. The most common is a deletion of phenylalanine at position 508 (ΔF508) [2] - this occurs in 66% of cystic fibrosis patients [1]. The cystic fibrosis transmembrane conductance regulator (CFTR) protein is an ATP gated chlorine ion channel found in epithelial cells at the apical surfaces. It belongs to the ATP-binding cassette (ABC) membrane transporter superfamily[4] and contains two membrane spanning domains, consisting of six transmembrane α-helices, and two nuclear binding domains (NBD) whose activity are regulated by the R (regulatory) domain (fig.1).

Cystic fibrosis (CF) is a progressive condition in which epithelial exocrine glands are obstructed (Howe, 2001). Whilst many organs and bodily systems are disrupted by CF, the lungs and gastrointestinal organs are predominantly affected; it is also most common amongst the Caucasian population due to the autosomal recessive gene (Quitter et al., 2003 cited in Wolfe & Mash, 2006, pg 514). The faulty gene effects the production of cystic fibrosis transmembrane conductance regulator protein, which is responsible for the formation of molecular tunnels which monitor the movement of salts and water from the cells (Hopkin, 2010 pg 4).

To understand the effects that Cystic Fibrosis has, it is important to discuss CFTR synthesis and trafficking. Mutations in the CFTR results in protein misfolding, causing a defect in cellular processing and trafficking that targets the protein for degradation and reduces the quantity of CFTR at the cell surface [56]. In order for the CFTR to function correctly, then it must be synthesized, folded, and transported to the apical membrane of the cell without problem. The CFTR passes through quality control systems to get rid of misfolded proteins that would not function properly or that could become damaged [16]. It is apparent that only 33% of CFTR folds correctly and is allowed to leave the endoplasmic reticulum [8]. The nucleus is the site

This gene provides information for making a protein that regulates the transforming growth factor beta (TGF-β) signaling pathway. The TGF-β pathway regulates many processes, including cell growth and proliferation, the process by which cells mature to carry out special functions (differentiation), cell motility, and apoptosis. By attaching to certain proteins , the SKI protein blocks TGF-β signaling. The SKI protein is found in many cell types allover the body and appears to have a role in the development of many tissues, including the skull, other bones, skin, and brain.

Finally, a paper published in September 2016 reveals that “frizzled proteins are colonic epithelial receptors for C. difficile toxin B” [22]. As they are introducing their studies of identifying potential TcdB receptors, they highlight some downfalls in previous studies, such as the fact that whilst CSPG4 was showed as an interacting receptor with Toxin B in HeLa and HT29 cells [17], CSPG4 is not actually present in the colonic epithelium [23]. Also, they comment on the fact that PVRL3 was shown only to be associated with TcdB cytotoxicity and not proof of PVRL3 acting as a receptor itself [13], however, there was evidence of PVRL3 interaction with TcdB, as discussed above [14]. This study used a genome-wide screen via CRISPR/Cas9 mutagenesis and identification of TcdB-resistant mutants, which identified the Wnt receptor frizzled family (FZDs) as TcdB receptors [22]. This mutant screening with native TcdB also confirmed CSPG4 as TcdB receptor and further studies showed it is CROP-dependent [17, 22]. The highest ranking mutant of plasma membranes when screened with the truncated TcdB1-1830 was FZD2, a member of the Wnt receptor frizzled family (FZDs) [22]. In healthy cells, the Wnt signaling, in which FZD proteins contribute to, are critical signal pathways involved in proliferation and self-renewal function of colonic epithelial cells [24, 25]. TcdB competes for Wnt to bind to these regions, inhibiting Wnt signaling, which in turn affects the health of colonic cells [22]. It

If the APC protein were to experience a nonsense mutation, the most common mutation in regards to this specific genetic disease, the destruction complex would not perform correctly and the wnt-signaling pathway would be stimulated. Problems begin to arise when “the Wnt/Beta-catenin pathway is activated [by] a Wnt ligand [binding] to seven-pass transmembrane Frizzled receptor and its co-receptor, low-density lipoprotein related protein 6 (LRP6) or its close relative LRP5” (MacDonald, et. al 2009). Once the wnt-signaling pathway is stimulated, a Wnt-Fz-LRP6 complex forms and takes in the Dishevelled (Dvl) protein, resulting in the phosphorylation and activation of the recruitment of the axin complex, destruction complex, to the receptors. (MacDonald, et al 2009). Due to the phosphorylation within the Wnt-Fz-LRP6 complex, the axin complex is not able to phosphorylate Beta-Catenin, which leads to the excessive accumulation of the protein in the cytoplasm. Researchers witnessed the development of numerous intestinal adenomas in transgenic mice with stabilized mutant Beta-catenin, therefore the results suggest that dysregulation of Beta-catenin is a key oncogenic event that follows the loss of APC function. (Tarapore, et. al 2011). The loss of the destruction complex’s normal activities results in elevated levels of Beta-catenin and downstream effectors such as CCND1,

The CTFR gene expression can be found in the apical membrane of skin cells in places such as the respiratory and gastrointestinal tracts. In the respiratory tract, a mutation in this gene causes excess secretions to be produced by the seromucous glands which in turn bog down the hair-like cilia, making the lungs unable to clear the excess fluid, bacteria or debris. This mutation can also cause this liquid-like layer to be thinner resulting in inefficient cilia. There is also an increased inflammatory response in patients suffering from CF, although the reasoning for this symptom is not yet quite understood. Altogether, these malfunctions lead to myriad of lung and respiratory issues including infection, a decrease in lung functioning, and eventually advanced lung disease (Davies and Bush, 2011).

A dysfunctional family is a group of people usually related by some means, not always necessarily by blood, in which conflict, misbehavior, maltreatment and neglecting create a hostile life for its members. To explain this idea better we will see the definition of family, the differences between a healthy and a dysfunctional family; their characteristics and behavioral patterns. Some examples will help us examine this issue better, taking us to discuss the different factors that contribute to the formation of such families, along with its consequences in today’s society.

DVL 1 protein is a cytoplasmic phosphoprotein produced by DVL 1 gene regulating the cell formations and a transducer particle for the developmental processes such as neuroblast specification and segmentation.1 In Wnt Signalling Pathway, the DVL 1 protein works by binding to C-terminus of frizzled receptors and transduce the wnt signal in both canonical and non-canonical pathway.2 These pathways activation lead to the accumulation of beta catenin protein in the cell which known to have important roles in proliferation and formation of the cells.2

Fermt1 has been studied widely with the focus on its function in keratinocytes. Herz et al., in

Families have their own ways of getting along and getting through tough and emotional times. Some talk it out and some even just give nothing but silence to each other. Some can't even forgive each other for years and years. All of that sounds so bad to go through. Even though there are those times of disagreement there are families who have a blast with each other. Theres so many different ways problems can be solved, but I love how unique my family gets through things. Now your views of a family being happy and my views are gunna be different. You may even say my views sound like an unhappy family. Even if you don't agree with my family ways doesn't mean it doesn't work. In this essay I'm going to try and show you my views both happy and unhappy families in my experience.

No one can’t meet a family like mine’s. My family is well diversified. Every family member plays an important role in all my family’s lives. In my family, there are four people: my father, my mother, my little brother and me. My father is one who brings money home and is also responsible for organizing and planning family trips. My mother is the one who is in charge for making meals and makes sure everyone eats at the appropriate times. My little brother is the pet of the family. He actually doesn’t have any responsibilities, for he’s the pet. I am the rock of support in my family. I always go beyond my parents’ expectations. I also support my younger cousins and little brother, by being a role model that they can look up to. Another