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150 Cards in this Set
- Front
- Back
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What is genomics?
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A branch of genetics that studies organisms by examining a complete genome
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Since most mammals have the similar numbers of genes, how is there such great variability?
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Genes are packaged in very different ways, ie number and size of chromosomes.
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How many chromosomes do dogs have? Cats?
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Dogs: 78
Cats: 38 |
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How do the genomics of animals relate to the genomics of humans?
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There are over 400 models for human disease found animals. (The dog alone has 224)
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Who was the first dog to have a genome sequenced and why?
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Tasha (boxer) was sequenced because she was found to be "most homozygous dog in America" Homozygosity allows easier sequencing because genomes do not have to be separated (mothers from fathers)
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Who was the first cat to be have a genome sequenced? Why?
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Cinnamon; descendent from cats with retinitis pigmentosa
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Why are there so many genetic disorders in dogs?
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Dog breeds were initially bred for function (working). During the industrial revolution in England dog breeding became a leisure activity (led to many of the toy breeds) along with the introduction of the show circuit, dogs were bred for phenotype. Increasing homozygosity and inbreeding led to the numerous genetic disorders.
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Why are we interested in studying dogs?
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1. They have the highest number diseases that are models for human diseases
2. Of the 38 million homes that have at least 1 dog, 55% are purebred dogs. there are huge issues related to vet med and health with so many genetic disorders in purebreds |
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What percent of purebred dogs are thought to be carriers for serious genetic disorders?
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Up to 25%
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Why are canine cancers thought to be appropriate models for human diseases?
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Many spontaneous cancers closely parallel the presentation, histology and biology of human cancers. ** Also** dogs and humans share similar genomes and environments
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How many chromosomes do canines have? How are they oriented?
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78 Chromosomes
all autosomes are acrocentric (have a centromere on one side of the chromosome) |
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How many breeds represent 75% of all the purebred dogs?
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20
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The rise and fall of breed popularities has had what types of consequences?
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Many have come from bottlenecks and therefore expose many genes that cause disease. Example: Rotties with osteosarcomas
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On the molecular level, what are the major problems with inbred dogs?
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They typically inherit an entire chromosomes which leads to high homogenicity because chromosomes are not a mix of parental genes.
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What are the major questions to be answered with tumor cytogenetics?
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1. How do we determine the nature of chromosomes abberations associated with tumors?
2. How do we determine which chromosomal aberrations are associated with cause and which with effect? |
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What is F.I.S.H?
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DNA analysis in which DNA clones are labeled with flourochrome dNTPs allow visualization of various bases within genes
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What are whole chromosome paint probes?
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DNA analysis in which entire chromosomes are labeled with flourochromes.
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What are the advantages of the direct analysis I using whole chromosome paint probes?
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1. Metaphase analysis
2. Translocation 3. Changes in copy number |
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What are the disadvantages of of the direct analysis I using whole chromosome paint probes?
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1. Interphase analysis
2. Intrachromosomal changes (inversions) |
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What is the Philadelphia Chromosome?
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The 1st consistent chromosome abnormality found in a neoplasm (chronic myeloid leukemia) and led to an advanced treatment.
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What is the Raleigh Chromosome?
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Shows that the Philadelphia chromosome is present in canine CML
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What is HYPP?
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Hyperkalemic Periodic Paralysis: Equine genetic disease which causes a defect in the sodium channel of nerves and results in increased levels of potassium causing paralysis of limbs. Can cause death if paralysis occurs in heart of lungs.
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What type of genetic disease is HYPP?
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Autosomal Dominant; point mutation
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How was the genetic cause of HYPP discovered?
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The champion 'Impressive', a famous Quarterhorse with outstanding conformation carried the defective gene. As a champion he sired thousands (by 1993 over 55000!) which caused HYPP to be an extremely common disease.
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What is HERDA?
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Hereditary Equine Regional Dermal Asthenia: genetic disorder which codes for dysfunctional collagen bundles within the dermis, which results in a lack of adhesion of the dermis. Skin separates during trauma and is slow to heal.
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What type of genetic disorder is HERDA?
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Autosomal recesssive; genetic tests now available for the genotype of the gene to determine if an individual is a carrier.
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What is freemartinism ?
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Chimeras (XX/XY) : Females which carry XY cells and cause infertility
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What causes Freemartinism?
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Affect mixed sex twins due to placental/vascular anastomosis. The Y chromosome produces hormones leading to female infertility.
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How common is freemartinism? How common is infertility in affected twins?
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85%; 90%
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How is freemartinism detected?
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1. Chromosomal analysis detects XY cells in circulating lymphocytes
2. PCR looks for presence of Y specific DNA |
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How is genomic being used in wildlife studies?
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1. Parentage verification of captive populations
2. Population analysis/assessment of genetic variability 3. Evaluation of wildlife diseases |
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What has caused the dramatic decrease (almost 80%) of the Tasmanian devil population?
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Tasmanian Devil Face Tumor
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What causes the tasmanian devil face tumor?
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Found to be an infectious cancer, passed on when another tasmanian devil bites the face of another (a common act in mating and fighting)
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How was the cause of the tasmanian face tumor discovered?
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The same genetic population of cancer cells was found on non related animals in different locations.
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Why are vasectomies being performed in some wild elephant populations?
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Some populations are overpopulated; reducing some males aids in biodiversity and conservations because it reduces the need for cullling and helps with management.
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How have genetic tests aided in the search for the cause of the urogenital carcinoma in California Sea Lions?
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20% of sea lions post mortum have aggressive urogenital carcinomas which were thought to be caused by a herpes virus; however individuals affected were found without the herpes virus. Paint probes on dog karyotypes show a shuffling of particular genes.
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What is transcription?
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DNA to mRNA
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What is translation?
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mRNA to amino acid sequence (protein)
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What are some of the signals that cells receive that can affect gene regulation?
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Hormones, toxins, medication
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What are some of the signals that cells receive that can affect gene regulation?
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Hormones, toxins, medication
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What are basic principle of gene regulation that allow a complex organism to regulate ~ 30,000 genes?
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1. Not all gene are expressed
2. Different genes are expressed in different cells 3. Many are regulated by increasing or decreasing production |
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What is signal transduction?
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A cascade of chemical messengers that typically occurs when an extracellular signal reacts with intercellular proteins that trigger a chemical pathway to control gene regulation
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What are transcriptors?
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proteins that bind DNA and can regulate gene expression
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How do transcriptors bind to the correct region?
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Uses the biochemical variations of the base pairs in very specific order to determine where the transcription factor can bind
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What is a codon?
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A three base pair combination that correlates with a specific amino acid
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What are the control mechanisms of gene regulation?
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1. Transcriptional control within nucleus
2. RNA processing control within nucleus 3. RNA transport 4. Translational control 5. mRNA degradation control 6. Protein activity control |
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What is the directionality of DNA?
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Antiparallel 3' to 5'
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What are the types of DNA mutations?
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1. Missense : change in an amino acid (deletions, insertions, point mutations)
2. Nonsense: introduction of stop codon 3. Silent: no effect 4. Frameshift |
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What are the types of RNA polymerase?
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1. rRNA: ribosomal RNA
2. mRNA, snRNA - messenger RNA 3. 5sRNA, tRNA - transfer RNA |
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What are the components of RNA polymerase?
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2 Large subunits and 10-15 smaller subunits
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What are the steps of transcription?
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1. Initiation
2. Elongation 3. Termination |
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How does the process of initiation occur?
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RNA polymerase recognizes and binds to a promoter sequence; DNA is locally unwound to permit transcription
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How does the process of elongation occur?
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New nucleotides are added to the 3' OH end of the RNA and the chain grows
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How does termination occur in transcription?
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RNA polymerase recognizes a specific nucleotide sequence that signals termination (stop codon sequence)
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What is polycistronic?
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Multiple bacterial genes can be clustered onto one long RNA
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What does monocistronic mean?
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One eukaryotic gene on each RNA
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What are the modifications that which turn pre - mRNA into mature mRNA?
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1. 5'cap
2. polyA tail 3. splicing 4. uses snRNA |
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What is the function of the 5'cap and polyA tail?
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To protect RNA from degradation
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What is splicing?
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The excision of introns from pre-mRNA by spliceosomes.
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What are promoters?
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DNA sequences that determine the site of transcription initiation for RNA polymerase
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What is the effective of differences in promoter sequences?
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The rate of transcription
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What do E. coli bacteria use to recognize different promoters?
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Different sigma subunits
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Where are promoters located in bacteria?
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-10 position, -35 position
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Where are promoters located in eukaryotic cells?
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-30 position
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What are transcription factors?
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Proteins that facilitate the initial binding of RNA polymerase II. Typically located distant (ie other chromosome) from the gene that it is regulating.
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What are the components of a transcription factor?
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DNA binding domain and a trans-activating domain (such as TFIIA, TFIIB) (domain consists of about 10 subunits)
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What are repressors?
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Transcription factors that inhibit transcription
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What are cis factors?
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A region of DNA located at ~30 (TATA) or ~80 (CAAT) position upstream from a gene that it regulates. Trans factors typically binds
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What are enhancers?
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Regulatory sequences that modulate the rate of transcription. May be located a great distance from the genes they control, or within the gene itself.
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What is chromatin?
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Genomic DNA complexed with proteins
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What are nucleosomes?
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Octamer of 4 different histone proteins complexed with DNA
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How does chromatin alter its structure during transcription?
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The histone proteins located within the DNA and can be acetylated and the chromatin structure is disrupted and allows transcription to occur.
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What are HRE's?
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Hormone receptor elements; Protein complexes located upstream of a gene that respond to the signal transduction of hormones which target the cell membrane. They can be within or overlapping promoters and enhancers.
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Describe the anatomy of a cell membrane
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The membrane is composed of two layers of phospholipids, with the hydrophilic head facing outward, and the hydrophobic head facing each other. Various proteins, receptors and pumps are located within the bilayer.
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What is is permeable and impermeable to a lipid bilayer?
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Permeable to small uncharged molecules
Impermeable to charged atoms/molecules Practically impermeable to ions |
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What are the types of proteins associated with the lipid bilayer?
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Peripheral Proteins
Integral Proteins Transmembrane Proteins |
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What are protein receptors?
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Proteins cause transmembrane signaling. An extracellular signal binds to the protein causing a conformational change that triggers signal transduction
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What are adhesion molecules?
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Integral proteins that can serve as physical contact point; they help with cell to cell adhesion, regulate growth, shape and differentiation. Ex: platelets
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What are the type of proteins that allow movement of solutes?
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1. Pores
2. Channels 3. Carriers 4. Pumps |
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What are pores?
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Integral proteins that allow the free movement of water, certain ions and molecules
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What are the types and functions of channels in a membrane?
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1. Voltage Gated: Open and close at certain voltages; allow ions to move down a concentration gradient
2. Ligand gates ion channels: open and close when a specific ligand binds to the protein allowing ions to move down a concentration gradient |
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What are carrier proteins?
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Proteins that facilitate transport of molecules across a membrane
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What are pumps?
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Proteins that use energy to move ions or molecule against a concentration gradient
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What is a uniporter?
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Channel that transports 1 molecule, typically down its concentration gradient
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What is a symporter?
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Channel in which one molecule is transported along with another ion, generally one is down a concentration gradient)
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What is the apical face of an epithelial cell?
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The side that faces the lumen; enzymes for digestion present. May have brush borders that increase surface area (ie in the intestine)
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What is the basal face of an epithelial cell?
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Faces the extracellular fluid, and in contact with the basement membrane. Na-K pumps present.
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What are the tight junctions of epithelial cells?
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Connect epithelial cells, prevent luminal fluid from surrounding the cell. Solutes and water can leak between tight junction from cell to cell.
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What is phagocytosis and pinocytosis?
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"Eating" cells
"Drinking" cells |
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What is Na-K ATPase pump?
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A membraneous symport pump that moves 3 Na+ ions out of the cell and 2 K+ ions into the cell. 1 ATP utilized for this exchange.
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How much energy of the basal metabolic rate is used to provide energy to the Na-K ATPase pump?
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Approx. 10%
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What is the the theoretical assumption of the Nernst equation?
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Equation that theoretically says that the electrical voltage=chemical gradient.
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Why is the Goldman Equation significant?
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In the calculation of RMP it includes calculations for variable ion permeabilities as well as the ion gradients.
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What is the resting membrane potential of a cell?
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-70 to -90 mV
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What are the relative extracellular concentrations of Na, K and Cl?
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Na: 140 mM
K: 4 mM Cl=116mM |
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What are the relative intracellular concentrations of Na, K and Cl?
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Na: 12 mM
K: 135 mM Cl=4 mM |
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How is the resting membrane potential created?
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1.The Na-K pump and relative permeabilities of K, Na and Cl create a chemical gradient for both K and Na.
2.As K tries to move down its chemical gradient and out of the cell it leaves behind large anions impermeable to the cell membrane. 3. The electric force created by the building negative charge inside the cell inhibits K to flow down its concentration gradient to a isotonic point. 4. The resting membrane potential is reached when there is no net movement of K ions. This leaves the cell with a negative charge inside, and a positive charge outside. |
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What is the sequence of actions in an action potential (general)?
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1. Stimulus
2. Depolarization 3. Repolarization 4. Hyperpolarization or undershoot |
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What occurs in the depolarization period of an action potential?
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Voltage gated Na+ gates OPEN and are ACTIVE.
Na+ flows down its concentration gradient into the cell, causing outside of the cell to become negative and the inside of the cell to become positive |
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What occurs in the repolarization period of the action potential?
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Voltage gated Na+ gates INACTIVATE (but are still open)
Voltage gated K+ gates OPEN K+ flows down concentration gradient out of cell |
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What occurs in the undershoot or hyperpolarization period?
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Some K+ gates close, but slower K+ gates remain open, allowing the cell to become hyperpolarized.
The Na+ gates close, but are now active |
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What is absolute refractory period?
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Period when Na+ channels are open and inactive.
No Na+ ions flow, channels cannot be opened to ANY stimulus. |
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What is the relative refractory period?
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Period when the cell is repolarizing. Na+ channels are closed, but active. A strong stimulus that could overcome the hyperpolarization might be able to cause an action potential
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Why are action potentials unidirectional?
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Because of refractoriness
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How is the strength of the stimulus determined by the action potential
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The frequency of the action potential
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What are postsynaptic potentials?
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Graded potentials created at the dendrites of cells.
They are created by neurotransmitters binding to receptors at the synapse. Local membrane potentials are graded in the amount of NT binding These graded potentials can alter the membrane at the axon hillock where an action potential could be generated |
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Where do EPSPs and IPSPs occur?
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At the postsynaptic membrane
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What type of gates do EPSPs target? What is the consequence?
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Open Na+ and K+ ion channels allow Na into the cell and K out of the cell.
Consequence is local depolarization |
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What type of gates do IPSPs target? What is the consequence?
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Open K+ ion channels allowing K out of the cell. Can also cause Cl- to enter the cell.
Consequence is local hyperpolarization |
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What are the ways signals can be integrated at the axon hillock?
Describe them. |
temporal or spatial summation
Temporal: how many signals the synapse receives over time Spatial: the integration of synaptic signals from multiple axons summating at the axon hillock |
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What are nociceptors? How do therapeutics target them?
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Pain pathways; local anesthetics and some antiepilectic drugs can target them by blocking Na+ channel from INSIDE the cell (drugs must get inside the cell membrane)
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What are examples of natural neurotoxins and how do the affect the nervous system on a molecular basis?
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Tetrodotoxin: pufferfish toxin
Inhibits voltage gated Na+ channels from opening Dendrotoxin: from Black Mamba Inhibits Volatge gated K+ channels |
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As a neurons diameter increases what is the effect on the speed of the impulse propagation?
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The speed increases
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What are schwann cells?
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Supportive cells of neurons that produce myelination.
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In what ways does myelination increase the speed of an impulse propagation?
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1. Insulation; decreased ion leakage
2. Saltatory conduction allows for the action potential to "jump" between the nodes 3. There is a high density of Na+ channels at the Nodes of Ranvier (in between schwann cells) |
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Where are peripheral ganglion located in the somatic nervous system?
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there are no peripheral ganglion
this allows for rapid, discrete control of motor neurons |
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What is a motor reflex arc?
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Stimulus target receptor
Sensory motor neuron integrates in spinal cord Effector neuron signals periphery neurons |
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Why is a withdraw reflex extremely rapid?
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The is no conscious component, the signal only has to travel to the spinal cord and back
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Define axosomatic
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Axon of one nerve cell synapsing with the cell body of another nerve cell
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Define Axodendritic
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Axon of one nerve cell synapsing with the dendrite of another nerve cell
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Define Axoaxonic
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Axon of one nerve cell synapsing with the axon of another nerve cell
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What are cholinergic nerves?
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Nerve that use Acetylcholine as a Neurotransmitter
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Where are cholinergic nerves located?
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1. Preganglionic nerves to ALL ganglia
2. Postganglion nerves in parasympathetic system 3. "Preganglion" nerves directly innervating the adrenal medulla 4. Postganglion; sympathetic neurons to sweat glands 5. All somatic neurons |
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What inactivates or decreases the amount of Ach in the synapse?
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Acetylcholinesterase (AChe)
Enzyme which breaks down Ach |
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What are adrenergic nerves?
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Nerves that use Norepinephrine (NE) as a NT
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Where are adrenergic nerves located?
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Postganglionic sympathetic nerves
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Where is NE synthesized from?
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Tyrosine
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How is NE limited or broken within the synapse?
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Limited through the neuronal reuptake by presynaptic neuron.
Small amount is metabolized by MAO and COMT |
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What ligands bind with adrenergic receptors?
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Norepinephrine (NT)
Epinephrine (hormone) |
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What are the types of cholinergic receptors and where are they located?
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1. Muscarinic : postganglionic, parasympathetic neuroeffector junction
2. Nicotonic a. Type I (ganglion) b. Type II (Neuromuscular junction) |
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What are the types of adrenergic receptors?
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1. Alpha 1,2
2. Beta, 1, 2, 3 |
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What are some physical changes that can occur when a ligand binds to a receptor?
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1. there is a shape change in the receptor that allows ions to flow through it
2. The receptor changes shape and causes the release of a 2nd messenger (ex: G protein) which can initiate a transduction pathway |
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What are the physiological interaction between ligand and receptor?
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Weak chemical bonds (such as H bonds or Van der waal's forces)
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Define Agonists
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Ligands that bind and activate receptors
Turn on the transduction mechanism |
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Define Antagonists
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Ligands which bind the receptors but DO NOT activate receptors
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What is the difference between competitive and noncompetitive binding?
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The length of binding and reversibility;
Competitive: permanent; nonreversible Noncompetitive: Does not bind permanently and can be reversed |
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What ultimately determines the physiologic response from the nervous system?
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The balance of opposing neurologic influences because organs are dual innervated by both the sympathetic and parasympathetic nervous system
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What are the effects of an adrenergic alpha 1 agonist?
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Vascular Smooth Muscle Contraction; increasing cardiac output
Increase in heart rate Mydriasis (iris dilation) (radial smooth muscle) |
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What are the effect of an adrenergic alpha 1 antagonist?
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Decrease in blood pressure
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What are the effects of an adrenergic alpha 2 agonist?
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Vasoconstriction, indirect decrease in heart rate as a protective measure
Modulation of NE release: the amount of NE released decreases with increased impulses by way of concentration dependent presynaptic A2 receptors. |
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Why are there presynaptic A2 adrenergic receptor?
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To conserve energy
Negative feedback is a protective mechanism of the heart. As vasoconstriction increases pressure increases, and the heart rate decreases to decrease pressure placed on vessels |
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What is the effect of an spinal adrenergic alpha 2 receptor agonist?
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Sedation; analgesics
Commonly targeted for epidurals |
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Where are B1 adrenergic receptors located?
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Myocardium
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What is the effect of a B1 adrenergic agonist?
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Increase Heart Rate
Increase Conduction speed, may cause arrhythmias |
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What are B1 adrenergic antagonists pharmacological use?
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Antiarrhythmias
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What are the effects of B2 adrenergic agonist?
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In vascular smooth muscle: evoke vasodilation and increase blood flow
In bronchial smooth muscle: evoke bronchodilation and decrease airway resistance |
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What are the effects of a B3 adrenergic agonist?
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Stimulate lipolysis by fat cells
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Where are muscarinic chonlinergic receptors located?
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Myocardium
Iris Sphincter GI tract Urinary Bladder |
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What are the effects of muscarinic agonists?
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Decrease HR
Evoke pupillary constriction (miosis) Peristalsis Urination |
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What two receptor are located on the myocardium?
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B2 adrenergic- increase HR
Muscarinic - decrease HR |
