Introduction Cells are the basic units of life. They communicate by sending and receiving signals. Signals may come from the environment or from other cells. In order to trigger a response, these signals must be transmitted across the cell membrane, and sometimes, cross the membrane. Once inside the cell, the signal continues on its way. Its ultimate destination depends on the nature of the signal, with some signals traveling to the nucleus or to other structures inside the cell. Signals most often move through the cell by passing from protein to protein, each protein modifying the next in some way. Collectively, the proteins that relay a signal to Once a signal reaches its target molecule (usually a protein), it works to change the behavior of the cell. Depending on the signaling molecules involved, the cell can respond in a variety of ways. Its destination makes up a signaling pathway. A signaling pathway can have few or many steps. Some signaling pathways branch out in different directions, sending signals to more than one place in the cell. As a signal is transferred from protein to protein, it can also be amplified. By dividing and amplifying a signal, the cell can convert a small signal into a large response.Cholera Cholera is an acute, diarrheal illness caused by infection of the intestine with the bacterium Vibrio choleraes and usually found in water or food sources that have been contaminated by feces from a person infected with cholera.  It is most likely to be found and spread in places with inadequate water treatment, poor sanitation, and inadequate hygiene.The cholera bacterium may also live in the environment in brackish rivers and coastal water such as in shellfish. Symptoms are mild, but can sometimes be severe, characterized by profuse watery diarrhea, vomiting, and leg cramps. In these people, rapid loss of body fluids leads to dehydration and shock. Without treatment, death can occur within hours. 1 The secretion of cholera toxin (CT) caused by the Gram-negative Vibrio cholerae bacterium can activate the cyclic AMP signaling pathway. CT is composed of a catalytic A subunit and five B subunits. The latter attach the toxin to the surface of the cell, where they function as membrane-penetration subunits that inject the catalytic subunit into the cell. The toxin interacts with a GM1 ganglioside on the cell surface of intestinal epithelial cells, and this enables the A subunit to enter the cell, where it stimulates fluid secretion by activating cyclic AMP formation. The catalytic A subunit catalyzes the transfer of ADP-ribose from NAD to an arginine group on the ? subunit of GS. This ADP ribosylation inhibits the ability of GS to hydrolyze GTP, which means that this G protein is locked in its active configuration and thus maintains a persistent activation of cyclic AMP and intestinal secretion, causing excess water loss. 2 While cholera can be severe, medication and other treatments can treat patients if action is quickly taken. Rehydration is the cornerstone of treatment for cholera. Oral rehydration salts and, when necessary, intravenous fluids and electrolytes, if administered in a timely manner and in adequate volumes, will reduce fatalities to well under 1% of all patients. Low-osmolarity oral rehydration solution and cereal-based oral rehydration solution are the preferred replacement fluids for most patients.  Zinc supplementation is another treatments and is said to significantly reduce the duration and severity of diarrhea in children suffering from cholera. In a study, all children received antibiotics and rehydration therapy as needed, but those in the intervention group also received zinc supplementation. Children who received zinc supplementation had 8 fewer hours of diarrheal illness and 10% less diarrheal stool volume, on average.  Zinc has also been shown to have a similar effect in children with diarrhea caused by infections other than cholera, 3Tuberculosis Tuberculosis is caused by bacteria that spread from person to person through microscopic droplets released into the air. This can happen when someone with the untreated, active form of tuberculosis coughs, speaks, sneezes, spits, laughs or sings.Although tuberculosis is contagious, it’s not easy to catch. Most people with active TB who’ve had appropriate drug treatment for at least two weeks are no longer contagious. Infection with HIV suppresses the immune system, making it difficult for the body to control TB bacteria. As a result, people with HIV are many times more likely to get TB and to progress from latent to active disease than are people who aren’t HIV positive. Another reason tuberculosis remains a major killer is the increase in drug-resistant strains of the bacterium. Since the first antibiotics were used to fight tuberculosis more than 60 years ago, some TB germs have developed the ability to survive, and that ability gets passed on to their descendants. Drug-resistant strains of tuberculosis emerge when an antibiotic fails to kill all of the bacteria it targets. The surviving bacteria become resistant to that particular drug and frequently other antibiotics as well. Some TB bacteria have developed resistance to the most commonly used treatments, such as isoniazid and rifampin.Some strains of TB have also developed resistance to drugs less commonly used in TB treatment, such as the antibiotics known as fluoroquinolones, and injectable medications including amikacin, kanamycin and capreomycin. These medications are often used to treat infections that are resistant to the more commonly used drugs.Medications are the cornerstone of tuberculosis treatment. But treating TB takes much longer than treating other types of bacterial infections. With tuberculosis, you must take antibiotics for at least six to nine months. The exact drugs and length of treatment depend on your age, overall health, possible drug resistance, the form of TB (latent or active) and the infection’s location in the body.Mycobacterium tuberculosis evades the rapid inflammatory responses used to attack foreign pathogens as part of the innate immune system. Once such pathogens are taken up into the phagosome, they are killed when hydrolytic enzymes are added during phagosome maturation. M. tuberculosis has developed various mechanisms to manipulate the host’s signaling pathways enabling it to survive and proliferate. In one mechanism, the bacterium subverts phagosome maturation by somehow switching off the Ca2+signals that are responsible for driving the maturation process. This inhibition seems to depend on lipoarabinomannan (LAM), which is one of the pathogen-associated molecular patterns (PAMPs), released from mycobacteria such as M. tuberculosis (Module 11: Figure formation and action of PAMPs). This LAM markedly reduces the Ca2+ signals that normally occur during the maturation processes. It seems that the LAM, presumably acting through Toll-like receptor 2 (TLR2), interferes with the phospholipase D (PLD) signaling pathway responsible for generating the Ca2+-mobilizing messenger sphingosine 1-phosphate (S1P). However, these pathogenic mycobacteria can be killed by macrophages if ATP activates an alternative Ca2+ signaling system through the entry of external Ca2+ following activation of P2X7 receptors Drug-resistant TB is caused by TB bacteria that are resistant to at least one first-line anti-TB drug. Multidrug-resistant TB (MDR TB) is resistant to more than one anti-TB drug and at least isoniazid (INH) and rifampin (RIF). Extensively drug-resistant TB (XDR TB) is a rare type of MDR TB that is resistant to isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin).Treating and curing drug-resistant TB is complicated. Inappropriate management can have life-threatening results. Drug-resistant TB should be managed by or in close consultation with an expert in the disease.Alzheimer’s Alzheimer’s is a type of dementia that causes problems with memory, thinking and behavior. Symptoms usually develop slowly and get worse over time, becoming severe enough to interfere with daily tasks. time. Alzheimer’s is a progressive disease, where dementia symptoms gradually worsen over a number of years. In its early stages, memory loss is mild, but with late-stage Alzheimer’s, individuals lose the ability to carry on a conversation and respond to their environment. Alzheimer’s is the sixth leading cause of death in the United States. Those with Alzheimer’s live an average of eight years after their symptoms become noticeable to others, but survival can range from four to 20 years, depending on age and other health conditions. It is not a normal part of aging. Memory problems are typically one of the first warning signs of cognitive loss. Symptoms include memory loss that disrupts daily life, such as getting lost in a familiar place or repeating questions, trouble handling money and paying bills, difficulty completing familiar tasks at home, at work or at leisure, decreased or poor judgment, misplaces things and being unable to retrace steps to find them. While medical management can improve the quality of life for individuals living with Alzheimer’s disease and their caregivers, there is currently no known cure for Alzheimer’s disease. Treatment addresses several different areas: Helping people maintain mental function, managing behavioral symptoms, and slowing or delaying the symptoms of the disease. Brain microvascular alterations are thought to contribute to the development of stroke and dementia. Structural changes in capillaries of elderly patients correlate positively with advanced age and dementia. The objective of this study is to use laser-induced fluorescence spectroscopy to compare structural (collagen content) and functional (apoptosis) parameters in brain tissues and isolated vessels of AD patients to age-matched controls. Our results show significantly higher fluorescent labeling for apoptosis in AD vessels compared to controls. Also, there is significantly higher autofluorescence (reflecting levels of collagen and other proteins that autofluorescence) in AD brain and vessels compared to controls. Western blot analysis of collagen subtypes shows elevated type I and type III and reduced type IV levels in AD vessels. These data demonstrate that changes in the amount and type of collagen occur in AD brain and suggest that cerebral vessel injury is part of AD pathology.In AD, a protein called beta-amyloid shows up in irregular clumps or clusters in the brain. This protein comes from a precursor protein found in a fatty membrane that covers nerve cells. The clumps of beta-amyloid fragments stick together to form plaque. These sticky clusters interrupt signals between synapses. Synapses are the spaces between nerve cells where information passes from one cell to another.In normal brain tissue, a protein called tau stabilizes microtubules. Microtubules are key parts of cell structure.In a diseased brain, protein strands, or threads, become tangled. As a result, the brain system of transporting cell nutrients In normal brain tissue, a protein called tau stabilizes microtubules. Microtubules are key parts of cell structure.In a diseased brain, protein strands, or threads, become tangled. As a result, the brain system of transporting cell nutrients along parallel structures — which can be compared to railroad tracks — falls apart. A marked feature of AD is a decline in autophagy, which seems to be associated with an increase in the activity of the mammalian target of rapamycin (mTOR). The InsP3R is known to play a role in autophagy by assembling a complex containing regulators such as Beclin-1, Bcl-2 and hVps34. The level of Beclin-1, which is a key component of the autophagy complex, is known to be reduced in AD. The decline in autophagy in AD may be related to an increase in the level of InsP3 that disrupts the autophagic complex by binding to the InsP3R. The drug Li+, which is known to reduce the risk of developing AD, can reduce this inhibitory effect by lowering the level of InsP3 as outlined in the inositol depletion hypothesis. Autophagy may also be reduced in AD by the elevated levels of Ca2+ that can disrupt the complex by activating hVps34. This activation of hVps34 may also account for the increase in mTOR that could explain the decline of autophagy in AD. The cognitive decline in mouse models of AD is reduced by rapamycin, which inhibits the activity of mTOR. Another role for mTOR is to phosphorylate Tau to increase its pathological role in AD. The elevation of Ca2+ can also stimulate CaMKK2 to increase the activity of AMP kinase (AMPK) that then enhances the phosphorylation of Tau thus contributing to the symptoms of AD.