Role of the Genes COLEC11 and MASP1 in Embryonic Development

Role of the Genes COLEC11 and MASP1 in Embryonic Development Vigneshwaree Sabapathy Mutations in the genes COLEC11 and MASP1 which code for lectin complement pathway proteins have been found responsible for a rare autosomal recessive disorder resulting in abnormal development. This proposes that other constituent proteins may play a role in embryonic development. To this day, the genetic aspects of the stages involved in embryonic development that leads to certain congenital disorders are still not fully understood. As a result, researchers start off with identifying the genes that play a part in causing a congenital disorder before determining how these genes bring about the disorder. This approach was adopted by Rooryck et al.1 to help prove that mutations in the genes COLEC11 and MASP1, involved in the lectin complement pathway were responsible for 3MC syndrome. The 3MC syndrome is an abbreviation of Michels, Mingarelli, Malpuech and Carnevale syndrome. These four syndromes are rare autosomal disorder that follows a recessive order of inheritance. The 3MC syndrome is characterised by blepharophimosis, ptosis of the eyelids, cleft lip and palate, craniosynostosis, hypertelorism and in some cases renal anomalies and umbilical hernia1,2. Furthermore, growth retardation, mental retardation and urogenital anomalies are also common features in all four syndromes2,3. After much research, it was found that the overlapping similarities in phenotype and Gestalt between these four syndromes are more significant than the differences between them2. Therefore, these evidence lead to the assumption that the syndromes are allelic variations of one another and belong to the same spectrum2. Rooryck and colleagues started off their study by first collecting DNA samples from individuals diagnosed with Michels, Mingarelli, Malpuech and Carnevale syndromes and all their available family members. Their genomes were then screened for single nucleotide polymorphisms which are homozygous in all affected individuals but absent in unaffected individuals. From the individuals tested, there were four consanguineous families. The genotyping results from members of these families showed a homozygous region of 2.2 MB at 2p25.3 in affected individuals1. Moreover, a region of homozygosity was found in two other families at 3q27.31,4. These findings suggest that the 3MC syndrome could be caused by multiple genes. From the sequencing of the open reading frames at the 2p25.3 region, 15 candidate genes were found, of which 9 were sequenced. Sequencing of these transcripts in affected individuals revealed three homozygous missense mutations and a single base deletion in COLEC11 that may be linked to the inheritance of the 3MC syndrome. Furthermore, the single base deletion in COLEC11 was found to play a role in the premature termination of the gene product CL-K1. CL-K1 is a C-type lectin that acts as a host defence by binding to carbohydrate antigens on microorganisms and activating the innate immune system5,6. Due to its function, it tends to circulate in the serum. In addition, being highly conserved in various species means that a mutation would be damaging to the function of the protein. Hence, to ensure that this mutation is an underlying cause of the 3MC syndrome, a protein blot assay was conducted to detect CL-K1 in the serum from two affected individuals. However, none was detected, indic ating a connection between the syndrome and the loss of function mutation in COLEC11. At the same time, the expression of CL-K1 was observed in certain mouse tissues that have been known to be affected by the disorder in humans1. In the same way, sequencing at the 3q27.3 region found 16 candidate genes potentially linked to the 3MC syndrome. One of these genes is the MASP1 gene which encodes for mannan-binding lectin serine protease 1 (MASP-1), a serine protease that is important in the lectin complement pathway4. Rooryck et al.1 then sequenced this gene in the two affected families and discovered two homozygous single base substitutions in exon 12. As predicted, the loss of function of this gene is consistent with the inheritance of 3MC syndrome. To study the effect of the loss-of-function of these proteins as well as to ensure that both the COLEC11 and MASP1 genes are accountable for the abnormalities witnessed in 3MC syndrome, knockdown studies were conducted using zebrafish. In these studies, two antisense morpholinos for COLEC11 were injected into one-cell stage embryos of zebrafish so as to imitate the loss-of-function of the gene. The same was done for the MASP1 gene. Based on the results from these studies, COLEC11 and MASP1 genes were found to cause similar phenotypes. The zebrafish morphants subjected to both these treatments displayed morphological abnormalities such as pigmentation and craniofacial cartilage defect similar to the symptoms of 3MC syndrome. Interestingly, when co-injected with a fully functional COLEC11 mRNA, the observed abnormalities in the zebrafish are reversed. Additionally, injecting a low dosage of both colec11 and masp1 morpholinos into the zebrafish embryos at the same time gave rise to simi lar deformities observed when injected separately, suggesting an interaction between the two genes5. Thanks to the pigmentation and craniofacial cartilage defects noted in zebrafish morphants, further studies were carried out to determine whether the CL-K1 and MASP-1 proteins are involved in the migration of cranial neural crest cells (NCCs) during embryonic development. Findings by Rooryck et al.1 in this part of the study revealed that beads coated with CL-K1 attracted NCCs when placed in the head region of zebrafish embryo. On the other hand, control beads implanted in the same region did not display the same attraction to NCCs. This proves the possibility that CL-K1 play a role in guiding the migration of neural crest cells. Similar results were also seen in a test using CL-K1 agarose disk and HeLa cells. At present, since the roles of both the COLEC11 and MASP1 genes in embryonic development have been discovered, more focus is required in investigating how the lectin complement pathway regulates embryonic development in addition to the role of the gene product, CL-K1 in early developmental processes. Likewise, the possibility of other constituent proteins and complement systems being involved in embryogenesis should also be considered. Therefore, further research on these aspects can help in the management of other congenital genetic disorders. (996 words) References: Rooryck, C. et al. Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome. Nat. Genet. 43, 197-203 (2011). Titomanlio, L. et al. Michels Syndrome, Carnevale Syndrome, OSA Syndrome, and Malpuech Syndrome: Variable Expression of a Single Disorder (3MC Syndrome)? Am. J. Med. Genet. 137A, 332–335 (2005). Kerstjens-Frederikse, W.S., Brunner, H.G., van Dael, C.M.L. van Essen, A.J. Malpuech Syndrome: Three Patients and a Review. Am. J. Med. Genet. 134A, 450–453 (2005). Sirmaci et al. MASP1 Mutations in Patients with Facial, Umbilical, Coccygeal, and Auditory Findings of Carnevale, Malpuech, OSA, and Michels Syndromes. Am. J. Human Genet. 87, 679–686 (2010). Hansen, S. et al. Collectin 11 (CL-11, CL-K1) Is a MASP-1/3–Associated Plasma Collectin with Microbial-Binding Activity. J. Immunol. 185, 6096–6104 (2010). Keshi, H et al. Identification and characterization of a novel human collectin CL-K1. Microbiol Immunol. 50, 1001-1013 (2006).

The Yalta Conference :: essays research papers

The Yalta Conference was one of the most important events in history, let alone, this century. It took place from February 4 to February 11, 1945, at Yalta, Crimea, a port/resort. The three main individuals at this meeting were Churchill of Great Britain, Roosevelt of the United States and Stalin of the U.S.S.R, known back then, and now known as Russia. This meeting was to discuss the post war effects. The publics opinion of this was of a great Anglo-American- Soviet friendship. The agreement that as achieved at the conference was that a Coalition government would be set up in Poland. This guaranteed free election in Poland. It also gave eastern Poland to the Soviet Union and in return, Poland would receive land from Germany. Germany on the other hand was divided into four zones which were Great Britain, United States, France, and the Soviet Union. Germany had to pay all reparations of the war but not to the extent of World War I. One other major decision made in the conference was the creation of the United Nations. This was a new world organization which worked for world peace as did the League of Nations. Along with the Soviet Union, Byelorussia and the Ukraine were admitted into the United Nations. Since Russia had influence on there voting, the United States was given 3 votes to be equal with the Soviet Union. After the conference, American public opinion was very high and all of the Allied nations responded favorably. There were also secret agreements that were made but kept secret until the end of the war. It was said that the Soviet Union were to enter the war against Japan two to three months after the end of the war in Europe. This was necessary in order for The Soviet Union to regroup because of the heavy causalities in Europe. The Soviet Union had a great advantage in the secret agreement. It received much land and did not have to do much in the end for it because of the use of the atomic bomb which ended the war much earlier then expected and the Soviet Union did not even have to fight Japan. In the classroom simulation of the Yalta Conference, the same results were not reached. The Soviet Union was not able to get most of its demands because in the classroom, most of the student looked at communism was not looked at very favorably.

Colonialism and the Struggles of the Black Psyche Essay

The book â€Å"Black Skin, White Masks† by Frantz Fanon analyzes the psychological damage that colonialism wrought on the colonizer and the colonized. Fanon also bases his analyses on his own experiences, wherein he describes how black children develop neuroses that root from their antagonism of their own skin, because of the media and their daily circumstances: â€Å"The dominant colonial culture†¦identifies the black skin of the Negro with impurity; and the Antilleans accept this association and so come to despise themselves† (Appiah ix). The source of â€Å"Black Skin, White Masks† is the psychological injury from colonialism, racism, and gender inequality, an injury that will escape recovery, unless the black psyche conquers its inner white demons and alienate all that alienates him/her. Fanon writes from the experiences and psychiatric analyses of the black skin and the white masks that black people don. He describes a girl who is afraid of black people: â€Å"†¦it is at this age that the Negro as savage and cannibal makes his appearance. It is easy to make the connection† (Fanon 184). This fear for the black skin is also emphasized and criticized in the painting â€Å"How Do You Like Me Now† (1988) (fig. 1) by David Hammons. This fourteen-by-sixteen-foot painting shows political leader Jesse Jackson with blond, wavy hair, blue eyes, pink cheeks, and white skin. The title is also a song of a popular rapper Kool Moe Dee. This painting can be interpreted from different perspectives. Barnwell and Buick argue that white viewers can see the painting from their perspective, wherein they are challenged to see through their biases and consider voting for a black man, now that he is â€Å"whitened. At the same time, the painting â€Å"asks black viewers whether they would support Jackson if he were white,† say Barnwell and Buick. On the other hand, the interpretation of the paintings also changes with the race of the artist. Barnwell and Buick explore the changes in meanings of the artwork, if Hammons race is changed from black to white. This painting has bee n attacked ten black men, who thought that it was racist and insulting, and they used sledgehammers to assail it and take it away from its scaffolding. Barnwell and Buick wonder if the black group would have still destroyed the painting, if they knew that the painter was black and that he was merely satirizing the color lines that enslave people’s minds. Clearly, blackness and whiteness release the innermost values and emotions of the people. The reactions can reflect the anger and despondency of the subjugated black race. â€Å"How Do You Like Me Now† (1988), as seen by the violent response of some people, has clearly marred the colonized. Colonialism has injured the black psyche to the extent that violence has been etched into it too. Colonialism has stripped black people of the right to define their identities, by caricaturing their existence and purpose in life. Colonialism, like slavery, skews the black people’s right to humanity and power. Violence, however, can regain this loss of power and replace the sense of loss. Through violence, the gap between power and powerlessness can be filled again. â€Å"How Do You Like Me Now† (1988) also remarks on the damage of colonization and racism to the colonizer. From the racist white perspective, this blonde man is a person who has greater potential for being a president. If faced with a black person, with black eyes and curly hair, the racist white would be offended with the overarching blackness. It will feel, like Fanon’s little girl who is afraid of black people, that they are being assaulted. The size of the painting also asserts power. But since colonial and white America would not consider any immense power from the black people, it is important to wear the white mask. With the black person masked as white, he will be accepted and he will have power. This is the same critique of Fanon of colonizers. The colonizers have forgotten that the black people also have their own identities. The whites see no black individuality and power, but only their whiteness. This seeing of whiteness on blackness marks another neurosis from the side of the whites. What is it about their whiteness that they have loved themselves too deeply and too irrationally? Following the analysis of Fanon, having power and asking for too much of it dehumanized the white race of the colonial times. That power is white has been embedded in their mind, an embedding that has been too violently engraved that to remove it also means to aggressively remove a part of them. Thus, the colonized is psychologically damaged too. But as the black people who hammered away â€Å"How Do You Like Me Now† (1988) showed, it is not acceptable to be a non-human being. It is not acceptable to be colonized and still feel like a normal human being. There must be catharsis. There must be freedom from all alienations. The painting â€Å"Wives of Shango† (n. d. ) (fig. 2) by Jeff Donaldson captures the liberation from three fronts- liberation of race, liberation of gender, and liberation from one’s own struggles. In this painting, three black women are adorned with bullets and money. The two are not looking back at the viewers, but have superiority in the way their chins are turned up. The middle woman at the back dares to look back at the viewers. But the expression is fierce, and it makes viewers look away. This painting is an image of power. This image breaks away the â€Å"comparaison† that Fanon talks about. Fanon argues that blacks are in the state of â€Å"comparaison,† wherein: â€Å"†¦he is constantly preoccupied with self-assertion and the ego ideal† (185-186). This preoccupation is about blacks being â€Å"always dependent on the presence of ‘The Other’† (Fanon 186). â€Å"Wives of Shango† (n. d. ) is interpreted as the shedding away of this â€Å"comparaison. It does not have a drop of submission or weakness. The women symbolize the power of their gender and race. They are willing to pay and kill to exert power. They are willing to dominate their personal struggles too, by fixing it through money and blood. But the means of money and violence, on the other hand, can also be interpreted as the product of the white gaze. Is it possible that these women are also still being white, by using the same arsenals of the white race? The white race entered and conquered through violence and money. Are the black people going to fight back with the same kind of brutal force? In doing so, they are â€Å"being white† too. Fanon argues that to be black, black people should also accept their whiteness. Fanon says: â€Å"I am French† (179), which includes being part of the white French culture. Fanon argues that the black people could not annihilate the whiteness in them. In the same way, white people can also not demolish the blackness inside them. White and black have mixed already, and this merging of two races and cultures cannot be ignored. Though the white demon has seeded inferiority complex in the black psyche, Fanon suggests that the way to recovery from the white’s subjugation is accepting â€Å"that which is white† in them. The alienation that black people feel is another problem, as it has divided the black psyche into numerous conflicting dimensions. Fanon says: â€Å"That this self-division is a direct result of colonialist subjugation is beyond question† (17). The alienation renders unspeakable psychiatric damages as it injects â€Å"compound, ambiguous, and unsettling results, both internally and externally† (Brown-Guillory 35). Fanon recommends a white mask, but not all people can wear it. â€Å"Wives of Shango† (n. d. ) detaches itself from the white mask. It stresses the power of the black psyche that can be hung outside in full glory. This black psyche might be afraid though, even when it is confident. The women wear symbols of violence and fighting. They know that re-locating their positions in power centers can have drawbacks, and they are prepared with ammunition. Alienation has corrupted the mind completely that fear has been entrenched in the actions and beliefs of the black people. This is where Fanon makes sense. Fear that alienation has created can only be undone through accepting the whiteness. It is also about mending the anger with peace, not with violence. The white mask does not represent another form of oppression. It symbolizes the feeling of safety and trust with whiteness. It signifies the end of domination of the black, because anytime, that mask can be removed. And fundamentally, it is still a white mask. Fanon makes several strong points. Racism, colonialism, and sexism have maimed the psyche of the white and black people. They are divided within, because of these oppressive experiences. But the blacks can recover from this damage, as long as they can handle wearing the white mask. At the same time, they must remember that the white mask is only a mask. It is important for the black people to also find their black identities and revel in the dignity of wearing it inside and out.

Gandhi Heros Journey Essay - 936 Words

Mahatma Gandhi once said, â€Å"You must be the change you wish to see in the world†. This shows that Gandhi believed in peaceful change. Gandhi was well known in India by many people. People were inspired by his ways and would stand by him in peaceful protesting. A lot of people believed in Gandhi as a hero. Just as well, Percy Jackson from the Lightning Thief is a known hero for stopping world WWIII between the gods. Both Gandhi and Percy Jackson follow the path of the hero s journey because they re both trying to complete a task. Mahatma Gandhi is a religious Indian who wanted independence from the British for his people. He wanted to do this in a peaceful way because he did not want violence. Mahatma Gandhi was called to adventure when†¦show more content†¦Percy is a hero because he saved the world of WWIII of the gods. In chapter 9 Percy starts his path on the hero s journey when he is called to complete a quest. The conversation is between the centaur Chiron and Percy. Your quest, of course. Will you accept it? I glanced at Grover, who was crossing his fingers. Um, sir, I said, you haven t told me what it is yet. Chiron grimaced. Well, that s the hard part, the details.Thunder rumbled across the valley. The storm clouds had now reached the edge of the beach. As far as I could see, the sky and the sea were boiling together.Poseidon and Zeus, I said. They re fighting over something valuable ... something that was stolen, aren t they? This shows that Percy was just called to adventure. Percy was ju st given a task to stop a war between the gods. This shows that Percy just stepped foot on the hero s journey since this was his call to adventure. â€Å"Percy starts his journey on the road of trials when HE ENCOUNTERS THE FURIES, WHO ARE HADES HELPERS. The text says â€Å"Annabeth and Grover moved up behind the Furies cautiously, looking for an opening. I took the ballpoint pen out of my pocket and uncapped it. Riptide elongated into a shimmering double-edged sword. The Furies hesitated. Mrs. Dodds had felt Riptide’s blade before. She obviously didn’t like seeing it again. â€Å"Submit now,† she hissed.Show MoreRelatedComparing the Journeys of Hesses Siddhartha and Gandhi Essay2049 Words   |  9 Pages      Ã‚  Ã‚  Ã‚   Siddhartha and Gandhi strove for different goals during their lives. Siddharthas goal was very personal, while Gandhis goal encompassed the world. This was shown by their spiritual development throughout their journeys. Siddhartha evolved from an inexperienced spiritual being to a man, returned to spirituality, and ended with nirvana. Gandhi traveled a much straighter path, originally being a worldly man merely seeking his correct place in life, when his spiritual development unexpectedly