Genetic Mapping of Innate Immune Defects.

Septic shock is a very dangerous medical condition that is described in your textbook on page 135. It is essentially an acute hyper-activation of the macrophage innate immune response, resulting in systemic (instead of localized) production of cytokines, with deleterious effects. Normally, local cytokine production at an infection causes “leakiness” in blood vessels, so that leukocytes can exit and migrate to the infection site (erythrocytes also leak out in the process, leading to the “redness” characteristic of inflammation). However, when cytokines are released throughout the body (“systemically”), then all the blood vessels become leaky (“vascular permeability”), leading to precipitous drops in blood pressure, and frequently organ failure and death. Septic shock has a 50% mortality rate, and is the leading cause of death in intensive care units (ICU’s) in hospitals.

One of the most common triggers of septic shock is LPS. In normal Gram-negative infections, this outer-membrane molecule is only present at the site of infection; however, if the bacteria reach the blood-stream, then LPS can quickly disseminate and trigger massive cytokine release throughout the body. This dangerous property of LPS led to its original name, “endotoxin”. (“endo” was meant to distinguish it from secreted “exo” bacterial toxins; unlike exotoxin virulence factors like cholera toxin, LPS/endotoxin is not a virulence factor evolved to exploit host cells).

Mice were often used to study septic shock, and a mouse strain that was resistant to septic shock was discovered in the 1960s. Normally, mice injected with LPS would succumb quickly to septic shock and death, but these mutant mice (C3H/HeJ strain) showed no effect upon LPS injection. On the other hand, when infected with live Gram-negative bacteria, the C3H/HeJ mice were unusually susceptible to infection and death.

In some ways, the C3H/HeJ mice were analogous to the boys diagnosed with CGD (chronic granulomatous disease) in the 1960s, in that both had heritable conditions that impaired immunity. A heritable defect implies the existence of a mutated gene that normally contributes to the affected process.

2a. The typical process for identifying an unknown gene that has a “phenotype” of interest is to “map” it to a particular chromosome, and then narrow its location to a smaller and smaller portion of this chromosome. Using animal models, this involves many generations, and tests of each generation to see which regions of which chromosome are always inherited in the individuals that exhibit the trait. This implies that chromosomes are not inherited intact from generation to generation: if chromosomes are strands of nucleotides covalently linked to each other, how is it that they are not inherited intact from parent to child?

2b. When mapping a trait in humans, instead of following inheritance through multiple generations (even if the disease status of ancestors is recorded, mapping is not feasible within family trees since DNA samples of ancestors were not preserved), researchers instead work with multiple independent families that seem to exhibit the same genetic disorder. For CGD genetic mapping, it was fortuitous that in the 1960s the disorder was identified in multiple unrelated patients. What feature of the CGD disease made identifying the affected gene a little easier by allowing the researchers to narrow their focus to a single chromosome?

2c. Is CGD a recessive or dominant genetic disorder?

2d. What traits or defects were observed in patients with CGD?

2e. Identifying the gene affected in CGD patients led to the discovery of an enzyme complex important in innate immunity. What is the name of this enzyme complex, and what does it do?

2f. The C3H/HeJ mice had a genetic syndrome with both beneficial and detrimental traits. In your own words, describe the beneficial vs detrimental aspects.

Scenario B: Vines, a small, popular chain of Italian restaurants, wishes to hire a new general manager to oversee a local restaurant's day-to-day operations. The company human resources manager posts an advertisement in the local newspaper stating, "General manager wanted for a fast-paced restaurant serving award-winning northern Italian cuisine. Applicants must have three years' experience in a comparable Italian restaurant managing a restaurant staff and ensuring the satisfaction of diners." In addition to making inquiries through industry contacts, the HR manager places the ad on the company's bulletin board and intranet. The HR manager then develops a pool of prospective candidates for the position and chooses from the pool of candidates when making decisions on whom to hire. The part of the ad in the local newspaper that stated that the company requires a general manger with three year's experience managing the restaurant staff in a successful Italian restaurant is an example of a job ________.

By now you have been introduced to the concept of measuring national output, or GDP. You know how GDP is calculated, and what its elements are. You also know that there are elements unaccounted for when calculating GDP. In other words, GDP is often underestimating national output. This article looks at household labor and unpaid labor, which are productive activities yet not included in GDP.

Should they be included in GDP? How do we approach in calculating them? What measures can we think of? In Folbre’s view, how has the failure to count household labor and production in official economic data had negative consequences, both on our economic understanding and economic policies?

Reuss' first article here addresses some criticism for the conventional measure of GDP, while his second article suggests a different measure, using Human Development Index. Folbre's article places economic valuation in the midst of today's coronavirus pandemic

The eardrum, which transmits vibrations to the sensory organs of your ear, lies at the end of the ear canal. In adults, that ear canal is about

2.5 cm in length. We can treat the ear canal as a tube, closed by the eardrum at one end, and open to the atmosphere at the external end. Consider a fluctuating air column in the canal: similar to a vibrating†string with one fixed end. Its fundamental frequency becomes half that of a string of the same length with both ends fixed. (You can convince yourself of this by imagining a tube with one end closed and the other end open. Sketch the node and antinode of the possible fundamental mode in the tube!)

f_n = nv/4L

Use the above equation to find what frequency standing waves can occur within the ear canal that are within the range of human hearing. The speed of sound in the warm air of the ear canal is 350 m/s. The audible range is 20 Hz to 20 KHz.

1-Describe what happens to the slope of the exponential phase for a population of tetracycline resistant bacteria growing in the presence of the antibiotic tetracycline. Explain what you have described.

2-In the article New Antibiotics Discovered by Sifting Through the Human Microbiome, the researchers discovered genes coding for the production of beta lactams, which targets bacterial cell wall synthesis. Because of this, beta lactams would be considered

a) Lysogenic

b) Cidal

c) Synthetic

d) Static

e)Exergonic

3-Hydroxychloroquine is used to control the replication of which of the following?

a)Plasmodium

b)Trypanosoma

c)Penicillium

d)Pseudomonas

e)Saccharomyces

4-. Nucleotide analogs stop DNA and RNA synthesis because they

a)Are not recognized by DNA or RNA polymerases

b)Do not allow the next nucleotide base to attach

c)Get incorporated by the ribosome

d)Are produced in high amounts by the cell’s metabolism

e)Are only used by eukaryotic cells

Assume that adults were randomly selected for a poll. They were asked if they "favoror oppose using federal tax dollars to fund medical research using stem cells obtained from human embryos."Of those polled,490were in favor,396were opposed,and 123were unsure. A politician claims that people don'treally understand the stem cell issue and their responses to such questions are random responses equivalent to a coin toss. Exclude the 123subjects who said that they were unsure,and use a 0.05

significance level to test the claim that the proportion of subjects who respond in favor is equal to

0.50.

What does the result suggest about the politicians claim?

The test statistic for this hypothesis test is?

The P-value for this hypothesis test is ?

Use the conclusion from the previous step to think about whether or not the statement made by the politician is accurate.

Please include calculation; I keep getting something wrong when calculating the test statistic.

Question 1. The height of a mercury column for atmospheric pressure at sea level is h = 0.760 + or - 0.003m of mercury (m-Hg).If the density of mercury is p = 13600 + or - 1000kg/m³ and the acceleration due to gravity, g = 9.8 + or - 0.1ms^-2 , determine the value of atmospheric pressure P_o = pgh and its uncertainty in SI units.

Question 2. A particle is moving in a straight line so that its velocity is given by the relation: v = (4.10 m/s²) t + 2.80 m/s. Calculate its average acceleration during the time interval from t₁ = 1.00s to t₂ = 5.00s.

Question 3. (a) Normal human blood contains 5.1 x 10⁶ red blood cells per cubic millimetre. The total volume is 5.5 litres. How many red blood cells does this man have? (b) What id the percentage uncertainty is the measurement 5.48 + or - 0.25 m?