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Bio Research Paper Writing

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Bio Research Paper Writing

Postby NathanielZhu » Thu Apr 04, 2013 2:25 am

My group and I are writing a research paper on the topic of "how do chronic viral infections contribute to immune senescence and how do they affect aging as a whole?"
We split the essay into parts and we brought it together yesterday:

Problem is, the other two group members are saying I wrote my part in a way that isn't how a research paper is supposed to be written....they're making it sound so bad like I have to rewrite the whole thing....

They wanted an intro for every topic (essentially they wanted an intro for every paragraph that is currently in my paper). I'm confused because why the heck would I need to write an explanation on how cytokines work or what is beta amyloid in a college research paper.
I guess what I'm trying to say is, in a research paper, do I need to tangent off to explain what topics like cytokines are before I explain the research on cytokines that answers the question....I would think background on cytokines are extraneous....since any science major ought to know it already

Anyways, it would be great if I had feed back on how a research paper ought to be formatted. Pardon my random spelling mistakes - my spellcheck is broken and please ignore my citations (the way I wrote them in this draft was just so I could make it easier on myself. It's not the final citations)

Also, since this is a group project, my part is 1/3rd of the entire report.
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Research Topic:
How do Chronic Viral Infections Contribute to Immune Senescence; how does immune senescence relate to aging as a whole?

Abstract
Age related immune-system decline in function may be more than self inflicted damage caused by improper controls and metabolic inefficencies due to evolutionary neglect. Chronic infections like HIV, CMV, and EBV alter immune function on every level: proteome, epigenome, signalsome, etc and as a result there is a clear phenotypic destinction between healthy immune system function and abnormal immune system between infected an noninfected individuals.

Immune System Aging
Immune senesence is associated with changes in the old as compared with the young. Notably, there is a huge change in the aging immune system of a cytomegalovirus (B-herperesvirus, HHV-5) infected person as compared to a person not infected with CMV. A 10 year study suggests that changes in blood T-cell distrubution did not happen in people not infected with CMV suggesting that changes in immune cell ratio may be the result of a viral disease rather than programmed inefficency (Immunity-Ageing np).

Chronic viral infections due to CMV have evolved mechanisms to defend against the adaptive and innate immune system, many of which target the function of the immune system and conversely, the immune system has evolved ways to resist these viral infections which is often inadequate. Viral infections pose a theat to DNA and so cell evolved a mechanism called DNA-damage response (DDR) to detect DNA lesions and to signal their repair (DNA-Damange-Response np). Chronic viral infections such as HIV, adenoviruses, herpes simplex 1 and 2, hepititis, EBV, and CMV trigger the DDR response (DNA-damange-Response). DDR serves as a front line of defense against the genetic changes associated with these viruses so viruses has evolved to evade the response. Two types of the human papilomma virus (HPV), type 16 and 18 produces a protein (E6) which is also responsible for many cancers (as will be discussed later) targets p53 (tumor supressor pathway) which results in the preservation of the virus by preventing apoptosis of its host cell (DNA-damage-response). Mechanistically, DDR-signaling in mammals are caried out by ATM and ATR which reduces cyclin-dependent kinases, many of which cross-talks with p53. CDK’s are then inhibited resulting in cell cycle arrest or is slowed down to increase DNA repair before division; simultaneously, ATM and ATR activate DNA-repair proteins to attempt DNA repair (DNA-Damange- Response np). When the cell can not repair itself nor can it trigger apoptosis, an alternative pathway is triggered resulting in cellular senesence which deprives the cell of its function and when many immune cells are put into this state, immune function becomes highly degraded (DNA-Damage-Response np). One mechanism that may explain how immune cells enter cell senesence is due to the effect of chronic viral infections on telomere function. Normally, telomerase isn’t active in most cells (which is an evolutionary advantage against cancer) and the shortening of the telomeres eventually results in ends that is recognised as double stranded breaks (DBS) which tiggers chromosomal break-fusion-bridge cycles that result in the formation of new telomeres (from sister chromatids) and as a result, a cell is able to continue functioning; however under circumstances of chronic DDR activation, cells do not undergo break-fusion-bridge cycles, but enter into apoptosis or senescence but since apoptosis is blocked, the cell enters senescence (DNA-Damage-Response np).


In addition to avoiding destruction by modulating DNA-Repair pathways, viruses also alter other aspects of the cell’s defense such as cell surface markers. CMV and adenoviruses decrease the expression of a cell’s MHC recognition markers which decreases the ability of the immune system to respond to infections that is highly characteristic of the immune system in senescence (DNA-Damage-Response np). One factor is the loss of the CD28 marker; when CD28 isn’t expressed, antigen-presenting cells like macrophages no longer recognise the T cell and thus aren’t able to alert the immune cell to danger (de Grey 207). Some viruses like HIV are able to prevent detection from the immune system by restricting the expression of virus antigens as well as having wide antigen variation (DNA-damage-response). Furthermore, there are viruses that modify other signaling pathways that lead affects lymphocyte and macrophage (which is an anti-gen presenting cell) functions that lead to immunosupression (DNA-damage-response). Persistent viral infection induced immune senescence act on every biochemical which in turn results in alterations in immune function at the cellular level. One key factor of immune senescence at the cellular level is overpopulation of old cells in senescence and differentiated cells with the goal of destroying an indestructible target. This is much like fighting multiple wars at the same with with one war being a Geurilla warfare. While the immune system mobilises B-cells to fight the guerilla war with the chronic viral infections like CMV, other viruses such as the common cold (Rhino viruses), the flu, bacteria, and other foreign invaders are able to overwhelm the immune system due to the lack of troops (naieve cells) to fight back. Cytomegalovirus, a herpesevirus is a very common virus that infects over 90.8% of people over the age of 80 (PLOS np). Since CMV results in a chronic infection, the immune system doesn’t reduce the number of specialized cells to fight the disease so there is an increase in counts of CD8 T cells and a decreased amounts of naieve cells and increased number of effector memory CD8 cells. This accumulation of unnecessary memory T-cells (termed memory inflation) has been shown to acumulate through the organism’s lifetime; CMV infection in mice has shown the reduced ability of CD8 cells to respond to influenca (PLOS np). Another type of cell that is persistently elevated in CMV infected patients is KLRG1 T-Cells which is a marker that prevents a cell from proliferating when there is no threat (Adding Exerpt from Ending Aging).


Signal disruption can be measured by an F-test of varience. A study of MCMV (mouse cytomegalovirus) using 5 coefficients of variability: VB9, VB9, VB10, and VB14 has shown that VB9, VB10, and VB14 varied significantly which suggests that signal disruption results in a malfunction in proper controls.


Immune aging is characteristic of a decreasing immune stem cell pool especially in the Thymus which is a central component that produces diferentiated immune cells of all types. This problem of thymus involution is also forcibly induced by viruses as a means of evading detection by the immune system. There is severe atrophy of the thymus in adult BALC/c mice infected by the mouse hepatitis virus A59 (Thymus-Involution np). This induced thymus involution by viruses is caused by modulated cytokine secretion due to the virus which results in apoptosis of immature T-cells (Thymus Involution np). As expected, studies have shown different expression patterns of the glycoprotein MHVR (MHV receptor) on thymus epithelial cells that are not present on T-lymphocytes (Thymus-Involution). Cytokine modulation that affect other systems such as the hematopoietic stem cell pool in the bone marrow may also indirectly affect the immune system by preventing T-cell progenitors to migrate to the thymus resulting in the decline of the amount of naieve cells. Because the thymus is such a sensitive target point for infectious agents not limited to the viral infections, studies have shown that mouse thymus have autoreactive thymus derived CD4 and CD8 T-cells capable of some defense function while still immature which correlates with the increased migratory cytokines that help mobilize immune cells around the body (thymus-common-target np) and these are the same cytokines which chronic viral infections like CMV damper down resulting in a chronically weaked immune response at the signalling level in addition to other major problems that arrise as a consequence like the accumulation of anergic cells (senesent immune cells that take up space/resourses without providing defense functions).


The Effect of Immune System Modulations on Systemic Aging
Immune senescence if an important topic to address because it addresses the decreased ability of the elderly of many model systems and humans to fight off infectious pathogens but it has much further significance in that the immune system also functions in cleaning up degraded products of during normal function of the organism system; for the immune system to be severely weakened by chronic viral infections that infect more than 80% of all individuals, it wouldn’t be surprising if many other systems are affect as well.


Cell signalling is a key role in how damage in individual cell function relates to the decline in function of entire systems. A disruption of a few processes may crosswalk to disrupting a cascade of other functions. Many of these signal disruptions caused by chronic CMV, HIV, and EBV infections lead to the upregulated inflamation in aged people by directly and indirectly modulating a variety of processes. A study was done in humans comparing cytokine production in CMV-negative and CMV-positive elderly and adult (Immune-nonhuman np). A compound, phorbol 12-myristate 13-acetate (PMA) was given to elderly and adults with CMV and without CMV; the collected data showed different CD8, CD4, and cytokine behavior between the groups (Immune-nonhuman np). In aged CMV-negative individuals, T-cell produced higher levels of the pro-inflammatory cytokine IL-6, IFN-y, and TNF-a upon longterm exposure to phorbol-12-myristate-13-acetate (Immune-nonhuman np). A later study confirmed the finding and added that CD8 T cells produced both type 1 (IFNy, IL6, TNF-a) and type 2 (IL4, IL6, IL10) cytokines; conversely in CD4 cells, there was a decrease in IFNy and TNF-a (Immune-nonhuman np). The findings in elderly CMV-positive individuals found a different trend in CD4/CD8 cytokine behavior. There was no increase in IL2 and IL4 but there was an increase in IFN-y and it is possible that the lack of IL2 and IL4 increase in CMV-positive idividuals contribute to the inflamation in the elderly and studies have shown that individuals with higher levels of inflamatory signals (chronic inflamation) are far more likely to die of age related diseases like heart disease/alzheimers than individuals without such characteristics.


One aspect of how chronic infections due to the cytomegalovirus may cause widespread malfunction is by modulating the mitochondria which is necessary for cell respiration. The virus produces a protein called vMIA which interacts with an endoplasmic reticulum molecule called Viperin (CMV-Vipirin). This results in the transport of viperin to the mitochondria where viperin interacts with mitochondrial proteins that is a part of pathways that catalyze B-oxidation of fatty acids that generate ATP. Studies on viperin suggest that normal B-oxidation is only affected by viperin with the iron-sulfer clusters which reduces the production of ATP (CMV-Vipirin np). Decreased ATP Production is associated with chronic inflamation of the liver other organs which is supported by studies on the motochondriopathies which are diseases that specifically result in abnormal mitochondrial function that results in ATP production that may exceed 30%. This results in swelling of organs and other life-threatening problems and so this observation may be the link between mutant mitochondria and the prevalent inflamation observed in the elderly.


Aging of the immune system is marked by higher risk of disease in several organis (lung, kidney, digestive, or nervous system) (Persistent-Viral-Infection np). According to Gladstone Institute, “HIV may serve as a model system for what we know about aging” (HIV-Premature-Aging np). Indeed people who are infected with HIV are dieing not so much from the directly effect of HIV on immune function but from the disease of aging “decades or two before earlier than their noninfected peers” (HIV-Premature-Aging). This is marked by having a much higher risk of having both heart attacks and strokes beginning when the individual is 50 as well as arthritis and dementia occuring decades before the average (HIV-Premature-Aging np). The trend is the same for the increased risk of cancer in HIV-infected individuals (HIV-Premature-Aging np).


Cancer is frequently observed in the elderly and rare seen in the young. At least partially, the immune system mediates apoptosis of early cancerous cells that randomly appear but in the elderly, the enviornment is such that the cell ignores internal and external signals to stop dividing. CMV and EBV is associated with lymphomas and carcinomas by modulating EBNA3A, EBNA3B, and EBNA3C (transcription regulators) that are responsible for transforming B cells into lymphoblastoid cells; in individuals with EBV, these oncogenes are upregulated resulting in repression of the pathways responsible for senescence like p16mk4A and pl4ARF (EBNA38-Deficent-Promotes-Cancer np). Recent studies are confirming confirming the idea of signal disruption that is characteristic of chronic viral infections in a study on cancer that is entirely independent of chronic infections caused by the Epstein-Barr virus and yet there is a strong pattern between cancer and EBV from many sourses (CD19-EBV np). The researchers in this case is using a virus to stop the cancer (that is most likely caused by another virus) by engineering T-cells (using a virus) that could detect CD19 expressed on the surface of B-cells. The result is that the T-cells destroyed the cancerous B-cells.


Alzheimer’s is a chronic neurogenerative disease that results in cognitive impairment and death. It is known to be caused by the build up of beta amyloid and neurofibilary tangles. Studies have shown that microgial cells in the brain attempt to engulf the build up of amyloid but is eventually overwhelmed. There is strong evidence to suggest that chronic viral infections of the herpese family (HSV1, HSV2, CMV, HHV6) plays a significant role in Alzheimer’s disease confirmed by PCR analysis in CMV infected alzheimer individuals and CMV infected elderly individuals without alzheimers; the data shows that CMV-infected elderly individuals with a certain allele of a lipoprotein (apolilipoprotein E allele type 4) are at a much higher risk of getting Alzheimer’s than CMV-infected individuals without the allele (Herpesvirus-Alzheimer’s np). In addition, nonallele specific HHV6 infections is present in 70% of individuals with Alzheimers suggesting that it contributes largely to the disease (Herpesvirus-Alzheimer’s np).


The overall system malfunction induced by CMV and EBV is also a frequent subject on the internet from desperate people seeking help and according to an individual, ““I was diagnosed with both EBV and CMV simultaneously 3 years ago (at 17), and have never been the same since. I was nearly bed-ridden for the better part of six months. Since then, I have had ongoing issues with my spleen, severe chronic fatigue, auto-immune issues, and joint pain/inflammation. I have a positive ANA and an elevated Sed Rate. Most recently I've been dealing with dizziness, shortness of breath, rapid heart rate, and anxiety”; the forum post is followed with a long list of CMV/EBV carriers experiencing the same problems.

References

1. (CMV Impairs immune Function)http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1002849\
2. (DNA Vaccinations)http://link.springer.com.mutex.gmu.edu/article/10.1007%2Fs00262-011-1107-2
3. (Thymus Involution https://www.ncbi.nlm.nih.gov/pmc/articles/PMC189556/
4. (Thymus-Common-Target )http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.0020062
5. (CMV-Vipirin-ppt) https://docs.google.com/viewer?a=v&q=ca ... hKt6L2xXwQ
6. (CMV-Induces-Vipirn) https://www.ncbi.nlm.nih.gov/pubmed/21527675
7. (Persistant Viral Infections) https://www.ncbi.nlm.nih.gov/books/NBK8538/
8. (HIV-Premature-Aging) http://www.sfgate.com/health/article/HI ... 893804.php
9. (DNA-Damage-Responce) http://www.nature.com.mutex.gmu.edu/nat ... 08467.html

10. (EBNA38-Deficent-Promotes-Cancer) http://search.proquest.com.mutex.gmu.ed ... /993084780

11. (EBV-CMV-Simultaneously) http://www.healingwell.com/community/de ... &m=1245667

12. (STOX1A-Alzheimers) http://www.sciencedirect.com.mutex.gmu. ... 4012012335

13. (Transhumanity-Ethics)
http://transhumanity.net/articles/entry ... se-ofaging

14. (The-Scientist) http://www.the-scientist.com/?articles. ... ls-Cancer/
15. (Science-Mag) http://news.sciencemag.org/sciencenow/2 ... tml?ref=hp
16. (Immune-nonhuman) http://www.sciencedirect.com.mutex.gmu. ... 6510001944
17. (CD8-Old-Population) http://www.sciencedirect.com.mutex.gmu. ... 6507001271
18. (Dementia-CMV)
http://www.ehealthme.com/cs/dementia+al ... +infection
19. (Fight-Aging) https://www.fightaging.org/archives/201 ... -aging.php
20. (Immunity-Ageing)http://www.immunityageing.com/content/7/1/13
21. (CMV-Inflamation-Cardiovascular) http://aje.oxfordjournals.org.mutex.gmu ... /172/4/372
22. (CD19-EBV) http://ncbi.nlm.nih.gov/pubmed/15679866
23. (Herpesvirus-Alzheimer’s) http://ingentaconnect.com/content/jws/p ... 3/art01127

:D
Why Do We Age?
http://hubpages.com/hub/Theories-on-Aging
Nature vs Nurture in Animal Behavior
http://hubpages.com/hub/Biology-Innate-Behavior-in-Animals
Photosynthesis
http://hubpages.com/hub/Understanding-Light-Dependant-Photosynthesis
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Postby JackBean » Thu Apr 04, 2013 7:27 am

Sorry, I didn't read the essay, but for sure scientific papers include introduction part from very broad range to your own topic (e.g. in my case I'd say what are cytokinins, how is it with cis-zeatin, metabolism of cytokinins and then what is known about zeatin isomerase; all this in introduction). That's because someone who is not familiar with the topic (either professional working with other proteins or student starting research with cytokinins) will read it, he or she needs some up-to-date introduction. This will also show your point of view and opinion about previous research. There are many free scientific papers at www.pubmed.com so if you want to check out what it looks like just go ahead. Maybe try some topic you're not so familiar with and you'll see how important the introduction is.

Anyway, your essay is only theoretical, right? You didn't do any research on your own, did you? In that case it's kind of introduction-only.
http://www.biolib.cz/en/main/

Cis or trans? That's what matters.
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