Movement of something through the community, are changed through evolution as the system becomes more organized

Diversity within functional groups such as keystone species groups so small perturbations don't overturn the population

Results in path dependency because the rules of interaction change as system evolves

Organization of components

The spread of diseases is affected by external factors such as sanitation and movement of people

Anyone coming in contact with someone who is immobilized due to the illness will get sick. The spanish flu spread so much because people were transported and were brought around other people which allowed for more spread

The viruses with a mild virulence stay in the population while the very viruelent ones blow through and don't stay in the population. If the pathogen can't easily infect hosts but is breeding quickly, it is not going to stay in the population since it is producing offspring for no reason. This means that evolutionarily, the rate of transmission would be favored over the rate of producing offspring. Inducing a change that allows for easier transmission will benefit more virulent strains because they are being compensated for what they can't do. Making transmission more difficult benefits the pathogens that can resist more time inside a host since they need to take more time before they can be transmitted

For vaccines, you want a virus that is less virulent so it produces more toxins so the vaccine can target it. Use inactive form of virus that doesn't produce toxin so the body can recognize the virus itself. Deadly bacteria is at an evolutionary disadvantage because we are producing vaccines against them.

Talk about virulence management: normally, it becomes "nicer" meaning less virulent so it can spread more. If it becomes more virulent then it will kill too fast and blow through the population. Some people say that this movement to less virulent is due to external management efforts (combination of pressures such as vaccination)

Transition areas between where there is high malaria vs. low malaria are very susceptible to variations in climate since slightly warmer can tip it towards more malaria

Shows different potential control mechanisms, changes in climate could predict the uprising of malaria, regarding rainfall they show that rainfall increses with altitude in ethiopia but decreases with altitude in colombia, chloroquine used to treat P. falciparum and show that the presence of these organisms is correlated with the temperature (for both so they are not specific to the parasite that is able to develop resistance)

Showing that as temerature mean is increasing you are also going up in altitude, also when you increase in altitude you increase in the percentage of cumulative cases. in the last section of panels blue is altitude and red is temperature, they match well in colombia but for ethiopia the overall trend is similar but not perfect, in both locations 1997 and 2002 there was a peak for the mean temperature and the altitude in the distribution, which could be attributed to the El Nino southern oscillation.

Showing correlation and overlap of altitude with cases of malaria

Over time, there were shown to be an increase in C over time (matches to the behavior for the number of trees and number of wildebeest) B- shows how each of the factors affect the change in ecosystem C, shows that grazing causes the greatest increase in carbon while fire keeps it relatively constant, left part of grass is high carbon source and right part is high carbon sink as there are more trees that can store more carbon and do not release much of it C- incorporating rinderpest into the availability of carbon (SOC is availability of carbon)

Show that presence of rinderpest affects wildebeests which then decreases the prevalence of fire For B they don't have data for how the grass affects things so that is why it is dotted

came up with 10 different models explaining the behavior of fires and tree cover, some factors proposed are wildabeests affecting fire by eating grass and preventing fire, if there's a lot of rain there's less fire, if more elephants theres less trees since elephants eat trees, CO2 concentration can directly affect concentration of trees or fire (but they don't show this), parameter DIC tells them which one is the best model (lowest model), third model (best) looks at wildebeest and seasonal rainfall, wildebeests have a higher impact because they have a lower DIC on its own (model 2)

D- looks at the trees over time Find that fire is the main determinant of tree cover A and D show a fairly similar pattern but D has a more modest change F- high correlation value showing that there is good correlation with the model explaining 3/4ths of the behavior and variability in data points (for fire) G- same as F but for number of trees H- plotting log of tree density at specific time point with the variability of the model and the data, shows that their model is more accurate for large tree density

showing that their model 3 is the best model (solid line), fits the fire-only model best, using the data from 81-03 to make their model and then predict backwards and check with the data to see if it matches. Cross-validation: more challenging than using the same data for all models, proves that their model is robust

Location of research, southeast area is covered by grass

Find what affects tree growth, find that fire and herbivores are main players in regulation of tree cover

recognizes protease and polymerase of MNV, shows where replication compartments are

mutate the K (lysine) since ubiquitination happens on lysine so switch it to arginine which is also basic,

Upstream or downstream of autophagy? neither. ATG5 would not be an autophagy function, not dependent on autophagy

Effector arm, not sensing and signaling

This means that it's not a canonical autophagy pathway? Or does this just mean that IFNy can override alpha and beta?

If there's p62, there's no autophagy

????

Do alpha and beta not have direct antiviral activity? Does this mean that IFNa/b generally create an antiviral state?

protrusions make the cell move, abrogations in the cellular membrane are protrusions

Basement membrane = ECM (extracellular matrix). Contributes to tumor metastasis and looking to see if there's any difference in patterns that can impact metastasis. Looking at if there is any difference between Ras and scrib, basement membranes are colored in Red.

Why the polarity mutations like shotgun contribute to metastatic behavior

Ventral Nerve Cord

Red means good, white means mutated

Can't make its own adenine

Identify mutations in Raf, MEK (downstream protein) and MAPK. depending on how mutant reacts they can group suppressor and enhancer in different categories and put them in different pathways. End up with a signaling pathway

There are many alleles and they do complementation assays. Point of complementation is if you cross 2 mutants and if both mutants die then they're probably the same gene. Do complementation to find groups of enhancers and suppressors.

cross mutagenated males with virgin females with balancer and get flies that are heterozygous for the mutation and have a balancer (stubble phenotype on balancer chromosome shows which ones got the balancer). Look for who has balancer and who also has variations in the rough-eye mutant

Need 2 balancers becuase they don't want to keep both because its not good for the animal so they have the gene on each of the balancers so they can have one animal with one balancer and one with another

Can only use one male because then you can cross it with many females

Need to put the P element on a TM3 (T2B) balancer chromosome and a curly wing balancer. How to get a P element on a balancer: need the fly to be heterozygous and contain a balancer chromosome. The way the paper does it, they inject the P element and transposase into regular fly and then cross them with flies with balancers and then add transposase to move the p element and see if the p element and the balancer chromosome segregate together (on the same chromosome)

Put in a P-element (transposable element to insert and a marker to see where the element was inserted) and use a rosy eye marker with a sev promoter so it will only be expressed in those cells. Also add the mutant form of Ras(V12)

Purpose: genetic screens to find how signaling pathway for eye development happens in flies (controlled by kinases and GTPases and G proteins). Looking for one mutation and enhancers and suppressors of mutation. Mutation is the rough eye phenotype that comes from a mutation in Ras1.

Homozygous Ras1 mutants are lethal

Dreams require experience about the world

Viral replication requires the production of various proteins, so how can this happen within the enclosure of the autophagosome? Does the assembly happen here, and if so, what indicates that all the necessary viral proteins must enter the autophagosome?

Explaining why the spontaneous mutation is not found in females since even if one gene is spontaneously mutated, the other copy of the gene would be fine. It can't be non-disjunction because the male would have a Y with the correct copy of the gene and since white is recessive, the male would be red eyed, so it must have arose through a spontaneous mutation

It would be heterozygous for color since one gene can be mutated and the other is ok. In this species the female is heterozygous for sex so female is XY and male is XX

Eye color factors are always connected with the X factor, so it is on the X chromosome. Males are always heterozygous for this mutation since the mutation is on the X chromosome and they only have one copy of it.

F1 and F2 both have white eyes. Do reciprocal crosses so white female with red male and white male with red female. The factor for red eyes is not on both chromosomes but only on the X chromosome. In the second cross, if the female has red eyes, all offspring have red eyes, but in the first cross, the males are white so it is sex linked.

When you cross white males and white females you only get white females, shows that white is recessive. Also shows that male and female shows up in equal ratio, so it really is recessive since the ratio is just the sex ratio

Dealing with F2 generation. Test the two classes of females (homozygous for red and heterozygous for red) and cross with white females

Checking if F1 females are heterozygous

Three and four are using males and females from F1, which all have red eyes. 4 is trying to prove that F1 males are heterozygous.

Saying there are two separate alleles for the W, but this is not the case since the W gene is on the X chromosome, not separate from it. It would just be W0

Produce 4 different genotypes where there are no females with white eyes, but there are some males with white eyes

All the F1 have red eyes

Two traits: Sex and eye color, says that sex is defined but eye color is not, males are heterozygous for X

These induce autophagy

Autophagosome is derived from the host ER and is formed by microtubule-associated protein 1 and its membrane homologs

Microautophagy: direct bulk uptake by lysosomes Chaperone-mediated autophagy: requires protein tag recognition to degrade small subset of proteins Macroautophagy: involved in host-pathogen interactions

Degradation of cellular material within the cells in the lysosome

We don't know how the shed viruses impact the immune system, and we don't know if it can be spread through respiratory routes.

Originally isolated in brain of mice from cranial injection, it affects the alimentary canal

~7000bp long

Class B biological agent that is transmitted in crowded locations and causes inflammation of the stomach and intestines (non-bacterial)

Infects immunocompromised mice without recombination-activating gene 2 and signal transducer and activator of transcription 1 (Rag2/Stat1) Rag2 arranges genes responsible for immunoglobulin and T-cell receptors STAT1 codes for downstream activation of cytokines and activate IL-17 pathway

Noroviruses are present in humans too but the mouse model is easiest to study

RPo happens first, initially attachment RPitc happens next and is the initial synthesis complex to intiate short transcription fragments RPc is after the initial short fragments when the elongation happens **experiment is putting certain factors in to induce the different stages of RNAP

Makes a little bit of RNA and then stops and then repeats at the start of translation before it is able to fully transcribe the gene

?????

Scrunching states that, instead of the RNAP being flexible, the DNA is, in that it is able to be pulled into the RNAP complex and forms single-stranded loops

Inchworming states that part of the RNAP is able to be detached (or at least is flexible) and can move downstream to continue transcription

In transient excursions, the whole RNAP molecule shifts across the DNA it is reading to form the RNA and then when it is done, it shifts back

The upstream portion of RNAP does not move, so either the other part of the RNAP is moving or the DNA is scrunching

Forms a loop of DNA. Is this what we saw in the image during lecture?

What is meant by abortive-product release ?

Different combinations of the models may be occurring or some models may be more efficient for certain tasks

When the normal acrIE3 gene in the DMS3m phage was replaced with acrIF1-F7 genes, most of the phages still succumbed to degradation by CRISPR/Cas. While some CRISPR inhibition occurred, most of the phages were destroyed. In a control phage lacking Acr genes, the phage was completely destroyed.

Upon first infection, some of the Acr proteins bind with CRISPR/Cas nucleases and inhibit them. Upon secondary infection, however, some of the nucleases are bound and inhibited, meaning the new phage's Acr proteins can bind and inhibit the rest of the nucleases, preventing CRISPR/Cas from functioning

There are two main classes of CRISPR/Cas systems. Class 1 uses more Cas proteins to degrade the DNA, while Class 2 only use one protein to cleave DNA

A segment of the bacteriophage's genetic material that is integrated into the host's genome

FosB upregulates expression of CDK5, which causes an alternation of nerve cell growth that gives nerves cells more dendrites, which would allow them to better receive signals from other parts of the brain. Since FosB is mainly found in the NAc, the extra dendrites would mean the signals from the rest of the brain such as the hippocampus and amygdala are stronger and cause a strong craving

FosB is only normally needed in the NAc, but higher usage of cocaine results in expression of FosB in other parts of the brain, showing how with more usage of cocaine it is more and more difficult to combat the addictive effects

High levels of FosB resulted in more intense highs and more of a craving for the drug, as mice would work up to 3 times as hard for the drug. This shows that cocaine's higher expression of FosB results in dependency and addiction

The frontal cortex allows for the decision process to occur where individuals can weigh consequences and choose the best course of action. Cocaine targets this by causing such a great feeling of pleasure that in the future, the decision to not take the drug again will be outweighed by this overwhelming feel of pleasure.

The hippocampus and amygdala are responsible for the memory that allows us to remember what made us feel pleasure, and cocaine affects this by making the user remember vividly what happened before the feeling of pleasure, such as where or under what circumstances the drug was used. This means that every time the user experiences these stimuli, they will remember the strong emotions associated with taking the drug and crave it.

The NAc is responsible for the feelings of pleasure and satisfaction since a large amount of dopamine-releasing cells are present here. This means that the NAc is primarily attacked by cocaine by the dopamine flood. Floods of dopamine are common, as there are natural stimuli that inhibit the regulation of dopamine, but cocaine acts stronger than these stimuli, giving a large rush of pleasure.

The dopamine system has been present for billions of years and is therefor essential to our survival, showing what a profound effect cocaine has on the body.

Normally, dopamine molecules are released into intercellular space and bind to receptors on other cells. Any remaining dopamine that has not been bonded to a receptor is pulled back into the dopamine releasing cells. Cocaine targets this inhibitory mechanism, preventing the regulation of dopamine and causing a large amount of dopamine to bind to cell receptors

ubiquitinates inhibitor proteins that allow NF-kB proteins free from the cytoplasm through activation of the IKK complex, dependent on RIP --TNF, TNFR, TRADD, TRAF2, RIP, MAK (some kinase), IKK activation (alpha, beta, gama, HSP90), phosphorylation of inhibitor protein IkB (hides NF-kB's nuclear localization sequence which normally allows it to enter nucleus), ubiquitination and degradation of IkB, allows NF-kB to enter nucleus and transcribe

TNF trimer binds to receptor, releases inhibitory protein silencer of death domains??? attracts RIP, TRADD, TRAF2, activates other proteis like caspases that cause apoptosis ---for apoptosis to occur all these things arrange in DISC complex, SODD prevents arrangement

multiple genes influencing each other? some transcription factors have multiple genes they regulate

???? how? some products from one pathway affect another?

macrophages produce this and then it sits on the cell surface?

has an early promoter?? also has a monomeric and dimeric form and the dimeric form is about 2x the size of the monomeric form so is it just that it's sometimes linked? expressed early in infection to evade immune system

??found in the open reading frame of terminal inverted repeats second gene from the outside on the accordion

interferes with proteins further downstream after tnf pathway is activated

binds with cellular TNF receptors to make a complex and dominates the complex

if it's a receptor homologue it binds to any tnf floating around

MT2 works to prevent apoptosis within the cell and doesn't really interfere with extracellular TFN but then how is it a TNF receptor homolog?

wild type virus with MT2 can infect RL2 CD4 t cells but when MT2 is deleted it can't infect because the cells can sense infection and go through apoptosis

deleting MT2 makes it less strong so it has something to do w virulence

functions only in myxoma since it doesnt block cytolysis in human or mouse

normal TNF receptors have 2-6 cysteine rich domains and MT2 has 4 that are used against apoptosis so it mimics regular TNF

Has multiple functions: inhibits extracellular TNF by acting as a decoy receptor and binding to TNF. Also acts intracellularly as a viromitigator to prevent apoptosis in infected T-cells

virokines are secreted proteins (decoys that bind to cell receptors to stop signaling) viroreceptors are decoy receptors that prevent signaling bc binding available cytokines

first 4 cysteine rich domains allow it to prevent TNF function. also, intracellular form can block apoptosis in lymphocytes using the first two cysteine rich domains

How can one protein be secreted as both forms? if it has two forms then is it really the same protein?

Expressed early in infection, have an affinity for host TNF-a so it inhibits the receptor which would normally activate the TNF pathway and cause apoptosis, needed for virulence in lab rabbits but deleted version still can infect even if you cut off part of the protein it still prevents apoptosis

Released continuously, not species-specific, deleting it means there is more inflammation at the site of inoculation and more immune cells infiltrate, main purpose is to stop chemokines from activating immune cells

Due to the inflammatory response set out by apoptotic cells, surrounding cells underwent apoptosis as well to prevent getting infected. could this speak to the intensity of the virus?

??? does this mean changes in way the virus infects and the host defends??

As rabbit chemokine receptors changed to not allow the virus in, the virus selected for certain genes that would allow it to bypass this defense (coevolution)

They replicate in cells with MHC II (dendritic cells)

SLS- standard laboratory strain UR- Uriarra (field strain)

Read from 3' to 5' so the genes towards the end are read and expressed later, but this gene is produced from the start of infection through late into the infection

M-T7 is another secreted protein from myxoma, and it showed that most of the secreted cells between 4 and 8 hours post infection are sensitive to endo H in BGMK cells, but the opposite is true for RL-5 cells (CD4+ cells?)

When M-T2 is produced, it goes about two ways. The first one is secreted through the Golgi body and is therefore protected from endo H, but some M-T2 is produced from a different method, making it susceptible to digestion by endo H

Even after M-T2 was produced, it was not modified to be protected against endo H, why would this be the case?

If the digestive enzyme endo H does not digest the proteins, it means they are farther along in the process of being created and transported, as they are already leaving the Golgi body and are protected from digestion

Sometimes, M-T2 is made and secreted quickly (2hrs post infection) but other times it sits in the cells and is not completely secreted, so depending on the progress of the infection, M-T2 production may be different

???????

M-T2 is mostly present in secreted form about 2 hours after infection and is not expressed much after the 12th hour of infection, which could suggest that this protein does not have as much to do with the actual infection process but more with the prevention of apoptosis so the virus can replicate

M-T2 is secreted but mostly functions from within the cell to stop apoptosis. This was shown because when purified M-T2 was introduced to the cells, they continued to undergo apoptosis

It's believed that M-T2 is just secreted, but when a virus with knocked out M-T2 infects a cell and extra M-T2 is added, apoptosis is not prevented, indicating that perhaps it is not simply secreted

Normally, TNF-a binds to TNF receptor and makes an antiviral state, but M-T2 binds to the TNF receptor and prevents this interaction from happening

Resembles the TNF receptor

Apoptosis is more organized so the cell does not release PAMPs so they produce TNF-related apoptosis-inducing ligands early (what do these do?). Necroptosis and pyroptois release PAMPs so the CD8 cells live longer and this is more immunogenic

??????????

E3 interacts with anti-viral agents such as interferons to prevent the detection and destruction of the virus and allowing it to replicate. It also inhibits apoptosis since when it is mutated the cells undergo death rapidly

vGAAP is similar to the human version (hGAAP) which has a transmembrane Bax-inhibitor-1 motif which contributes to the prevention of innate apoptosis. Additionally, GAAP is hydrophobic and is located in the Golgi apparatus, forming a large ion channel to let in Ca+ ions, which can contribute to anti-apoptotic effects

Does not directly cause apoptosis but it does interact with Bax because it has folds resembling Bcl-2, which can cause the slowing of the innate immune response but will not necessarily directly cause anti-apoptotic effects

Binds in the mitochondria to Bax, Bak, and sometimes Bim to prevent mitochondrial apoptosis. By binding to these proteins, it does not let them carry out their normal function of causing the cell to go through apoptosis. It also inhibits inflammasome formation, meaning the host's body is not responding to infection and so the virus can keep replicating unbothered

Expressed early during infection, found in every orthopoxvirus which suggests that it is required for infection to occur

??? something to do with the membrane around a fetus?

?????????

Protein B13 similar to CrmA and found in rabbitpox

Normally, ICE/caspase1 is the main enzyme that triggers the apoptotic response, but CrmA was found to inhibit apoptosis by binding to and inhibiting ICE/caspase1

??????

Cell explodes and releases factors that cause inflammation in neighboring cells, thus attracting more immune cells to destroy the virus

When caspase-8 is unable to work properly, the necrotic kinases RIP are activated and activate downstream effectors when caspase-8 can't do that

how does the RNA activate TLR3?

What's the difference between ripoptosome, necrosome, and apoptosome? is it just that they activate apoptosis in different ways?

What's the difference between pro-caspase and caspace?

Ligands on the outside of the cell bind to receptors and the interactions that result from the binding signals the formation of the DISC complex that activates pro-caspase 8

Mitochondria releases cytochrome c which causes the production of the apoptosome, but viral proteins (in red) inhibit the various functions of caspases which, if found in large concentrations, can stop apoptosis

BH3 and BCL2 proteins work together to regulate apoptosis but how does this work? is it like a checks and balances thing?

How apoptosis works: signal is received to undergo apoptosis, cell begins breaking down from within by caspases organized by BCL-2 proteins, and all the celular debris is packed into apoptotic bodies to reduce the effects on other cells, apoptotic bodies consumed by phagocytes

?? has something to do with inflammation?

When IFNa/BBP was deleted in vaccinia, the IFN pathway was active in both test conditions and in WT

When infecting mice with GAGmut, the virus will enhance T-cells and NK cell responses which will cause a detection of the virus, but since it is only mutated and not deleted, it can still cause disease

When a mouse has antibodies for IFNa/BBP then it can recognize the virus and destroy it so it will block infection, proving that this virus is important in virulence

???

IFNa/BBP absence caused lower virus replication in spleen and liver. IFNa/BBP(GAGmut) caused a slight reduction in organs, which points to IFN-1 playing a part in allowing the virus to replicate in major organs. Deleting IFNa/BBP resulted in healthy mice

IFNa/BBP are not required initially for the replication of viruses in vivo in natural conditions (footpad innoculation)

Protein E194 was present in the cells when the GAG mutation was not done, meaning the IFN pathway could not be blocked

How does this work?

Also show that B18 contributes to cell interaction but does not bind and block IFN-1

When the gene for B18 was deleted, the VACV was 100 times weaker, and it was even weaker in ECTV since B18 contributes to preventing the creation of an antiviral environment

Doesn't have part of protein that corresponds to being in the membrane but is still located on the surface of cells. It's an IFNa/BBP and it binds to uninfected cells which prevents IFN to communicate with neighboring cells.

Proteins are secreted that bind to IFN-1 and don't allow it to interact with receptor, serve as decoy receptors (IFNa, and BBPs)

Does this just mean releasing immune factors that destroy the virus?

Family of cytokines that cause inflammation by being secreted from infected cells upon detection of viral material. Also transmit signals to healthy neighboring cells to start the transcription of interferon stimulated genes to create an antiviral state

Added expression of MC159 to mice, found that immune cells would proliferate and not go through apoptosis as much inhibits cell death so allows cells to proliferate

?? Family of proteins charatarized by DEDs, two DED in tandem which serve as protein protein interaction domains, cell has cFLIP (cellular flip) which is important for inhibiting cell death, MCV makes two FLIPs 159 and 160 which inhibit cell death, inhibit NFkB

cause for the development of antibodies allows for the study of about how many people have had it, if they have antibodies that means they prob had it

What is abortive infection? Cannot grow in culture, innitiates infection, early gene transcription, cytopathic effects and the cell recovers (this is why it can't be grown)

How do cells that produce keratin impact the fitness of the virus? Cells are always dividing, so this allows the virus to multiply, can only be in this cell

If a virus inhibits this by binding, it reduces its chances of being killed

Need both death effector domains in the gene for MC159 to properly function

Appears and is localized in the cytoplasm, inhibit TNF and procaspase-8 ability to cause apoptosis

Focus on type I interferons (IFNs)

such as keratinocytes?

cannot be cultured and grown, hard to understand how it is transferred from animal to animal

Proteins that simulate the proliferation of keratinocytes and stop apoptosis so virus can keep replicating

M11L has a transmembrane domain that allows it to insert itself into the outer mitochondrial membrane to prevent degradation, which would normally lead to apoptosis

?? Contains specific structure that allows for protein-protein interaction, also M-T5 is not homologous to anything in a host

?? Makes myxoma able to stay in the ER?

Myxoma Growth Factor, similar to Epithelial Growth Factors, required for the progression of infection and the ability for the virus to spread through the organism

Rabbits infected with mxyoma deficient in Serp-1 would recover from the disease and become immune when exposed to it again. There was a heightened inflammatory response, but it was less severe.

M-T7 is secreted most during myxoma infection. In vivo, the gene is needed for productive virulence. M-T7 KO in rabbits allowed for more leukocytes that destroyed the virus

M-T2 (dimeric form) inhibits apoptosis due to the tumor necrosis factor

?? can have one or two units?

M-T1: can be knocked out and virus will still function, prevents cell ligands from binding to their receptors

Virokines- secretions by the virus to bind to normal cellular receptors

Viroreceptors- similar to regular cellular receptors, can inhibit extracellular host ligands - which stops the inflammation process