Podcast
Questions and Answers
What is the primary function of cell-to-cell communication in multicellular organisms?
What is the primary function of cell-to-cell communication in multicellular organisms?
Which type of signaling involves hormones traveling through the circulatory system?
Which type of signaling involves hormones traveling through the circulatory system?
Which communication method allows substances to pass freely between adjacent cells?
Which communication method allows substances to pass freely between adjacent cells?
What is an example of local signaling?
What is an example of local signaling?
Signup and view all the answers
Which of the following is NOT a form of local communication?
Which of the following is NOT a form of local communication?
Signup and view all the answers
Which type of cell-to-cell communication involves immune cells and antigen presenting cells?
Which type of cell-to-cell communication involves immune cells and antigen presenting cells?
Signup and view all the answers
In paracrine signaling, what type of substance do secretory cells release?
In paracrine signaling, what type of substance do secretory cells release?
Signup and view all the answers
What role do hormones play in plant long-distance signaling?
What role do hormones play in plant long-distance signaling?
Signup and view all the answers
What effect does ligand binding have on G protein coupled receptors (GPCRs)?
What effect does ligand binding have on G protein coupled receptors (GPCRs)?
Signup and view all the answers
Which of the following accurately describes a function of GPCRs?
Which of the following accurately describes a function of GPCRs?
Signup and view all the answers
What is the role of ligand gated ion channels in cellular signaling?
What is the role of ligand gated ion channels in cellular signaling?
Signup and view all the answers
What is homeostasis in biological systems?
What is homeostasis in biological systems?
Signup and view all the answers
What happens to GDP during the activation of a GPCR?
What happens to GDP during the activation of a GPCR?
Signup and view all the answers
Which component is required for a GPCR to activate its associated G protein?
Which component is required for a GPCR to activate its associated G protein?
Signup and view all the answers
What initiates the process of cellular response in ligand-gated ion channels?
What initiates the process of cellular response in ligand-gated ion channels?
Signup and view all the answers
Which of the following is NOT a form of feedback loop involved in homeostasis?
Which of the following is NOT a form of feedback loop involved in homeostasis?
Signup and view all the answers
What are the three stages of cell signaling?
What are the three stages of cell signaling?
Signup and view all the answers
What is the role of a ligand in cell signaling?
What is the role of a ligand in cell signaling?
Signup and view all the answers
What happens during the transduction phase of cell signaling?
What happens during the transduction phase of cell signaling?
Signup and view all the answers
What can result from mutations in receptor proteins involved in signaling pathways?
What can result from mutations in receptor proteins involved in signaling pathways?
Signup and view all the answers
Which of the following is a consequence of faulty signal transduction pathways?
Which of the following is a consequence of faulty signal transduction pathways?
Signup and view all the answers
How do signal transduction pathways influence cellular response?
How do signal transduction pathways influence cellular response?
Signup and view all the answers
What is the primary function of protein kinases in cell signaling?
What is the primary function of protein kinases in cell signaling?
Signup and view all the answers
Signal transduction pathways can ultimately lead to which of the following?
Signal transduction pathways can ultimately lead to which of the following?
Signup and view all the answers
What occurs during the reception stage of cell signaling?
What occurs during the reception stage of cell signaling?
Signup and view all the answers
What type of molecules do plasma membrane receptors typically bind to?
What type of molecules do plasma membrane receptors typically bind to?
Signup and view all the answers
Which of the following best describes transduction in cell signaling?
Which of the following best describes transduction in cell signaling?
Signup and view all the answers
What is a common role of second messengers during the transduction stage?
What is a common role of second messengers during the transduction stage?
Signup and view all the answers
Which enzyme is responsible for phosphorylating proteins during signal transduction?
Which enzyme is responsible for phosphorylating proteins during signal transduction?
Signup and view all the answers
What is the primary function of intracellular receptors?
What is the primary function of intracellular receptors?
Signup and view all the answers
During cell signaling, what does dephosphorylation primarily do?
During cell signaling, what does dephosphorylation primarily do?
Signup and view all the answers
Which of the following statements about receptors is true?
Which of the following statements about receptors is true?
Signup and view all the answers
What does a change in the shape of a receptor usually indicate?
What does a change in the shape of a receptor usually indicate?
Signup and view all the answers
Which type of receptor would most likely bind to a steroid hormone?
Which type of receptor would most likely bind to a steroid hormone?
Signup and view all the answers
What is the primary effect of negative feedback in biological systems?
What is the primary effect of negative feedback in biological systems?
Signup and view all the answers
Which is an example of a positive feedback mechanism?
Which is an example of a positive feedback mechanism?
Signup and view all the answers
What role do histones play in DNA organization?
What role do histones play in DNA organization?
Signup and view all the answers
What condition may lead to a homeostatic imbalance?
What condition may lead to a homeostatic imbalance?
Signup and view all the answers
What are homologous chromosomes?
What are homologous chromosomes?
Signup and view all the answers
Which of the following statements is true regarding the cell cycle?
Which of the following statements is true regarding the cell cycle?
Signup and view all the answers
What triggers the release of oxytocin during childbirth?
What triggers the release of oxytocin during childbirth?
Signup and view all the answers
During which phase do sister chromatids become visible?
During which phase do sister chromatids become visible?
Signup and view all the answers
Which of the following is NOT a characteristic of the genome in eukaryotes?
Which of the following is NOT a characteristic of the genome in eukaryotes?
Signup and view all the answers
Which scenario exemplifies a homeostatic response to high temperatures?
Which scenario exemplifies a homeostatic response to high temperatures?
Signup and view all the answers
What is the role of cyclins in the cell cycle?
What is the role of cyclins in the cell cycle?
Signup and view all the answers
How do cyclin-dependent kinases (CDKs) activate cell cycle progression?
How do cyclin-dependent kinases (CDKs) activate cell cycle progression?
Signup and view all the answers
What is contact inhibition in relation to the cell cycle?
What is contact inhibition in relation to the cell cycle?
Signup and view all the answers
In what way do cancer cells differ from normal cells in terms of division?
In what way do cancer cells differ from normal cells in terms of division?
Signup and view all the answers
What distinguishes a malignant tumor from a benign tumor?
What distinguishes a malignant tumor from a benign tumor?
Signup and view all the answers
What is the primary reason cancer cells can continue to grow uncontrollably?
What is the primary reason cancer cells can continue to grow uncontrollably?
Signup and view all the answers
Which external factor can trigger the activation of CDKs in the cell cycle?
Which external factor can trigger the activation of CDKs in the cell cycle?
Signup and view all the answers
What genetic change is primarily associated with the transition of normal cells to cancer cells?
What genetic change is primarily associated with the transition of normal cells to cancer cells?
Signup and view all the answers
Study Notes
Unit 4: Cell Communication and Cell Cycle AP Biology Topic 4.1/2/3/4 Cell-to-cell communication is critical for the function and survival of cells Responsible for the growth and development of multicellular organisms Cell Communication 1.Direct Contact 2.Local Signaling 3.Long-distance signaling Cells communicate through three general ways How Do Cells Communicate? Direct Contact Direct contact: communication through cell junctions Signaling substances and other material dissolved in the cytoplasm can pass freely between adjacent cells Animal cells: gap junctions Plant cells: plasmodesmata Direct Contact Example: Immune cells Antigen presenting cells (APCs) communicate to T cells through direct contact Local Regulators Local regulators: a secreting cell will release chemical messages (local regulators/ligands) that travel a short distance through the extracellular fluid The chemical messages will cause a response in a target cell Examples: Paracrine signaling Synaptic signaling Local Regulators Paracrine signaling: secretory cells release local regulators (ie growth factors) via exocytosis to an adjacent cell Local regulator Target cell Secretory cell that acts on nearby cells Local Regulators Synaptic signaling: Occurs in animal nervous systems Neurons secrete neurotransmitters Diffuse across the synaptic cleft- space between the nerve cell and target cell Neurotransmitters Axon Synaptic cleft Target cell Animals and plants use hormones for long distance signaling Plants release hormones that travel in the plant vascular tissue (xylem and phloem) or through the air to reach target tissues Animals use endocrine signaling Specialized cells release hormones into the circulatory system where they reach target cells Long Distance Signaling Long Distance Signaling Example: Insulin Insulin is released by the pancreas into the bloodstream where it circulates through the body and binds to target cells Quick Check What type of communication involves a cell secreting a substance to an adjacent target cell? Plant cells in direct contact with each other can diffuse substances through these structures to communicate. What are they? 01 02 Quick Check What type of communication involves a cell secreting a substance to an adjacent target cell? Answer: paracrine signaling Plant cells in direct contact with each other can diffuse substances through these structures to communicate. What are they? 01 02 Quick Check What type of communication involves a cell secreting a substance to an adjacent target cell? Answer: paracrine signaling Plant cells in direct contact with each other can diffuse substances through these structures to communicate. What are they? Answer: plasmodesmata 01 02 Card Sort Practice Problems How do you think cells process signals? Cell Signaling: Overview Cell-to-cell messages can be divided into three stages 1.Reception Ligand binds to receptor Cell Signaling: Overview Cell-to-cell messages can be divided into three stages 1.Reception Ligand binds to receptor 2.Transduction Signal is converted C e l l S i g n a l i n g : O v e r v i e w C ellt o - c ell m e s s a g e s c a n b e divid e d in t o t h r e e s t a g e s 1 .Re c eption L i g a n d b i n d s t o r e c e p t o r 2 . Tra nsdu cti o n S i g n a l is con v erte d 3 .Response A cell proc ess i s a ltere d A B C Stage 1: Reception Reception: the detection and receiving of a ligand by a receptor in the target cell Receptor: macromolecule that binds to a signal molecule (ligand) All receptors have an area that interacts with the ligand and an area that transmits a signal to another protein Binding between ligand and receptor is highly specific Stage 1: Reception When the ligand binds to the receptor, the receptor activates (via a conformational change) Allows the receptor to interact with other cellular molecules Initiates transduction signal Receptors can be in the plasma membrane or intracellular Stage 1: Reception Most common type of receptor involved in signal pathways Bind to ligands that are: Polar, water-soluble Large Examples: G protein coupled receptors (GPCRs) Ligand-gated ion channels Found in the cytoplasm or nucleus of target cell Bind to ligands that can pass through the plasma membrane Ie hydrophobic molecules Steroid and thyroid hormones Gasses like nitric oxide Plasma Membrane Receptors Intracellular Receptors Stage 1: Reception Intracellular receptors Note: the AP exam will not expect you to be able to classify any given molecule as hydrophobic, usually they will either tell you it is hydrophobic, or they will say the molecule is a steroid hormone Stage 2: Transduction Transduction: the conversion of an extracellular signal to an intracellular signal that will bring about a cellular response Requires a sequence of changes in a series of molecules known as a signal transduction pathway Intracellular signaling molecules Stage 2: Transduction The signal transduction pathway regulates protein activity through: Phosphorylation by the enzyme protein kinase Relays signal inside cell Dephosphorylation by the enzyme protein phosphatase Shuts off pathways *Remember: a change in shape means a change in function Intracellular signaling molecules © Getting Down With Science Stage 2: Transduction During transduction the signal is amplified Second messengers: small, non-protein molecules and ions help relay the message and amplify the response Cyclic AMP (cAMP) is a common second messenger Intracellular signaling molecules Stage 3: Response Response: the final molecule in the signaling pathway converts the signal to a response that will alter a cellular process Examples: Protein that can alter membrane permeability a. Enzyme that will change a metabolic process b. Protein that turns genes on or off c. A B C Quick Review What are the three stages of cell signaling? 01 What is the actual “signal” being transduced in a signal transduction pathway? 02 How is this “signal” passed from outside to inside the cell? 03 Quick Review Answer: reception, transduction, reponse What are the three stages of cell signaling? 01 What is the actual “signal” being transduced in a signal transduction pathway? 02 How is this “signal” passed from outside to inside the cell? 03 Quick Review Answer: reception, transduction, reponse What are the three stages of cell signaling? 01 Answer: a ligand What is the actual “signal” being transduced in a signal transduction pathway? 02 How is this “signal” passed from outside to inside the cell? 03 Quick Review Answer: reception, transduction, reponse What are the three stages of cell signaling? 01 Answer: a ligand What is the actual “signal” being transduced in a signal transduction pathway? 02 Answer: through transduction. During transduction the signal is relayed by protein kinases and amplified by second messengers How is this “signal” passed from outside to inside the cell? 03 Signal transduction pathways can influence how a cell responds to its environment They can result in changes in gene expression and cell function Can alter phenotypes or result in cell death Signal Transduction Pathways Mutations to receptor proteins or to any component of the signaling pathway will result in a change to the transduction of the signal Changes in Signal Transduction Pathways S o m e dis e a s e s, s u c h a s c a n c e r a n d dia b e t e s, a r e c a u s e d b y d e f e c tiv e p r o t ein p h o s p h a t a s e s. E x plain h o w s u c h a d e f e c tiv e p r o t ein w o uld a f f e c t a sig n al transduction pathwa y. Practice FRQ In eukaryotic organisms there are two main categories of cell membrane receptors: G protein coupled receptors (GPCRs) Ion channels Important Receptors G protein coupled receptors (GPCRs): Largest category of cell surface receptors Important in animal sensory systems Binds to a G protein that can bind to GTP, which is an energy molecule similar to ATP GPCRs GPCRs ligand The GPCR, enzyme, and G protein are inactive until ligand binding to GPCR on the extracellular side Inactive enzyme Inactive G protein Inativate GPCR GPCRs Ligand binding causes cytoplasmic side to change shape Allows for the G protein to bind to GPCR Activates the GPCR and G protein GDP becomes GTP GPCRs Part of the activated G protein can then bind to the enzyme Activates enzyme Amplifies signal and leads to a cellular response Ion Channels Located in the plasma membrane Important in the nervous system Receptors that act as a “gate” for ions When a ligand binds to the receptor, the “gate” opens or closes allowing the diffusion of specific ions Initiates a series of events that lead to a cellular response Ligand gated ion channels: Ion Channels © Getting Down With Science Topic 4.5 The body must be able to monitor its internal conditions at all times Set points: values for various physiological conditions that the body tries to maintain This set point has a normal range for which it can fluctuate Example: body temperature Set point: 98.6℉ Normal range: 97℉ to 99℉ Overview Overview Homeostasis: the state of relatively stable internal conditions Organisms detect and respond to a stimulus Think: balance The body maintains homeostasis through feedback loops Feedback loops There are two types of feedback loops: negative and positive Terms to know: Stimulus: a variable that will cause a response Receptor/sensor: sensory organs that detect a stimulus. This information is sent to the control center (brain) Effector: muscle or gland that will respond Response: changes (decreases or increases) the effect of the stimulus The most common feedback mechanism This type of feedback reduces the effect of the stimulus Examples: Sweat Blood sugar Breathing rate Negative Feedback Example: Negative Feedback Happy Patrick Sweaty Patrick Shivering Patrick Stimulus: heat Receptor: temperature receptors in skin Effector: sweat glands Response: sweat Stimulus: cold Receptor: temperature receptors in skin Effector: muscles Response: shivering Body temperature regulation This type of feedback increases the effect of a stimulus Examples: Child labor Blood clotting Fruit ripening Positive Feedback Example: Positive Feedback Childbirth Stimulus: baby pushes on cervix Receptor: nerve cells in cervix send signal to brain Effector: pituitary gland releases oxytocin Response: Oxytocin stimulates contractions Homeostatic Imbalances There are many reasons for why the body may not be able to regulate homeostasis For example: Genetic disorders Drug or alcohol abuse Intolerable conditions (ie extreme heat or cold) Homeostatic Imbalances Disease: when the body is unable to maintain homeostasis Examples: Cancer: the body cannot regulate cell growth Diabetes: the body cannot regulate blood glucose levels Cell Signaling as a Means of Homeostasis In order to maintain homeostasis, the cells in a multicellular organism must be able to communicate Communication occurs through signal transduction pathways © Getting Down With Science Topic 4.6/7 Cell Cycle The cell division process is an integral part of life Allows for the reproduction of cells, growth of cells, and tissue repair Cell cycle: the life of a cell from its formation until it divides Organization of DNA Cells must organize and package their DNA before division DNA associates with and wraps around proteins known as histones to form nucleosomes Strings of nucleosomes form chromatin When a cell is not actively dividing, chromatin is in a noncondensed form After DNA replication, chromatin condenses to form a chromosome Chromosomes are densely packed to allow for easier division Organization of DNA The copies join together to form sister chromatids Centromere: the region on each sister chromatid where they are most closely attached Kinetochore: proteins attached to the centromere that link each sister chromatid to the mitotic spindle Since the DNA was replicated, each chromosome has a duplicated copy Genome Genome: all of a cell’s genetic information (DNA) Prokaryotes: singular, circular DNA Eukaryotes: one or more linear chromosomes Every eukaryote has a specific number of chromosomes Humans: 46 Chimps: 48 Elephants: 56 Genome Homologous chromosomes: two chromosomes (one from mom and one from dad) that are the same length, have the same centromere position, and carry genes controlling the same characteristics Practice FRQ Biological structures tend to be composed of smaller units that assemble into more complex structures. Using eukaryotic chromosomes as an example, a) describe the smaller units and their assembly that leads to the larger, more complex structure of a chromosome. b) Identify one major function of chromosomes. Types of Cells Body cells Diploid (2n): two sets of chromosomes, one set from each parent Divide by mitosis Humans: 2n=46 23 from mom 23 from dad Reproductive cells (eggs/sperm) Haploid (n): one set of chromosomes Divide by meiosis Humans: n=23 Somatic Cells Gametes Cell Cycle Cell Cycle The cell cycle consists of alternating phases of interphase and mitosis G₁→ S→ G₂ → mitosis → cytokinesis Interphase Cell Cycle Interphase The longest portion of the cell cycle (90%) G1 “first gap” phase The cell grows and carries out normal functions S “synthesis” phase DNA replication and chromosome duplication occurs G2 “second gap” phase Final growth and preparation for mitosis M Phase Mitosis: nucleus divides Cytokinesis: cytoplasm divides Mitosis results in 2 identical diploid daughter cells Phases of Mitosis Mitosis is broken down into 5 stages: 1.Prophase 2.Prometaphase 3.Metaphase 4.Anaphase 5.Telophase and cytokinesis Prophase Key events: Chromatin condenses Nucleoli disappear Duplicated chromosomes appear as sister chromatids Mitotic spindle begins to form Centrosomes move away from each other Prometaphase Key events: Nuclear envelope fragments Microtubules enter nuclear area and some attach to kinetochores Metaphase Key events: Centrosomes are at opposite poles Chromosomes line up at the metaphase plate Microtubules are attached to each kinetochore Anaphase Key events: Sister chromatids separate and move to opposite ends of the cell due to the microtubules shortening Cell elongates Telophase and Cytokinesis Key events: Two daughter nuclei form Nucleoli reappear Chromosomes become less condensed Telophase and Cytokinesis Cytokinesis occurs Animals: a cleavage furrow appears due to a contractile ring of actin filaments Plants: vesicles produced by the Golgi travel to the middle of the cell and form a cell plate © Getting Down With Science Tracking Chromosomes Parent cell 2n=2 2 chromosomes Maternal chromosomes Paternal chromosomes After S phase 2 chromosomes 4 chromatids 2n=2 daughter cells 2 chromosomes Anaphase 4 chromosomes Human Cells: Tracking Chromosomes © Getting Down With Science Can you identify stages of mitosis in the image below? Practice Multiple Choice Movement of the chromosomes during anaphase would be most affected by a drug that prevents 1. A) nuclear envelope breakdown. B) cell wall formation C) elongation of microtubules. D) shortening of microtubules. E) formation of a cleavage furrow Practice Multiple Choice Movement of the chromosomes during anaphase would be most affected by a drug that prevents 1. A) nuclear envelope breakdown. B) cell wall formation C) elongation of microtubules. D) shortening of microtubules. E) formation of a cleavage furrow Practice Multiple Choice 2. Eukaryotic chromatin is composed of a.condensed DNA only b.DNA and RNA c.DNA and carbohydrates d.DNA and proteins e.DNA and ribosomes Practice Multiple Choice 2. Eukaryotic chromatin is composed of a.condensed DNA only b.DNA and RNA c.DNA and carbohydrates d.DNA and proteins e.DNA and ribosomes Practice Multiple Choice 3. If a sperm cell contains 12 chromosomes, it comes from an animal that has __ chromosomes. a.4 b.8 c.12 d.16 e.24 Practice Multiple Choice 3. If a sperm cell contains 12 chromosomes, it comes from an animal that has __ chromosomes. a.4 b.8 c.12 d.16 e.24 Practice FRQ A cell has 50 chromosomes. After mitosis and cell division, you find that one daughter cell has 49 chromosomes and the other daughter cell has 51 chromosomes. Predict one way that this could have happened. Regulation of the Cell Cycle Throughout the cell cycle there are checkpoints Control points that regulate the cell cycle Cells receive stop/go signals Major Checkpoints G₁ Checkpoint Most important checkpoint Checks for cell size, growth factors, and DNA damage Stop/Go signals “Go”- cell completes the whole cell cycle “Stop”- cell enters a nondividing (quiescent) state known as G₀ phase Major Checkpoints G₀ Some cells stay in G₀ forever (muscle/nerve cells) Some cells can be called back into the cell cycle Major Checkpoints G₂ Checkpoint Checks for completion of DNA replication and DNA damage “Go”--cell proceeds to mitosis “Stop”-- cell cycle stops and the cell will attempt to repair damage If damage cannot be repaired the cell will undergo apoptosis Programmed cell death Major Checkpoints M (Spindle) Checkpoint Checks for microtubule attachment to chromosomes at the kinetochores at metaphase “Go”--cell proceeds to anaphase and completes mitosis “Stop”-- cell will pause mitosis to allow for spindles to finish attaching to chromosomes Internal Cell Cycle Regulators Regulation of the cell cycle involves an internal control system that consists of: 1.Proteins known as cyclins Concentration of cyclins varies Cyclins are synthesized and degraded at specific stages of the cell cycle Enzymes known as cyclin-dependent kinases (CDKs) 2. Concentration remains constant through each phase of the cell cycle Active only when its specific cyclin is present Notice: varying levels of different cyclins in each stage Internal Cell Cycle Regulators Each cyclin-CDK complex has a specific regulatory effect Active CDK complexes phosphorylate target proteins, which help regulate key events in the cell cycle External Cell Cycle Regulators Growth factors: hormones released by cells that stimulate cell growth Signal transduction pathway is initiated CDKs are activated leading to progression through the cell cycle Contact (or density) inhibition: Cell surface receptors recognize contact with other cells Initiates signal transduction pathway that stops the cell cycle in G₁ phase Anchorage dependence: cells rely on attachment to other cells or the extracellular matrix to divide Cancer: Evasion of the Cell Cycle Normal cells become cancerous through DNA mutations DNA mutations: changes in the DNA Cancer cells on average have accumulated 60 or more mutations on genes that regulate cell growth Normal Cells vs Cancer Cells Do not follow checkpoints Divide infinitely when in culture Considered to be “immortal” Evade apoptosis and continue dividing even with errors Follow checkpoints Divide on average 20-50 times in culture (in petri dishes) Go through apoptosis when there are significant errors Normal Cells Cancer Cells Cancer Cells The uncontrollable growth of cancer cells can lead to a tumor A mass of tissue formed by abnormal cells Benign tumor: cells are abnormal, but not considered to be cancerous (yet) Cells remain at only the tumor site and are unable to spread elsewhere in the body Malignant tumor: mass of cancerous cells that lose their anchorage dependency and can leave the tumor site Metastasis: when cells separate from the tumor and spread elsewhere in the body Cancer Prevention Unfortunately, cancer can affect anyone. However, there are various things that you can do that will minimize your risk of developing cancer: Do not smoke (cigarettes, vape products) Nicotine causes mutations in cells at high rates Eat healthy and drink water Fatty foods and dehydration can affect the functions of cells Protect your skin from the sun by using SPF Sun is damaging to skin cells and can cause mutations to occur after exposure If possible, ask your family about any history of cancer and receive regular cancer screenings Practice FRQ Vinblastine is a chemotherapeutic drug often administered to patients suffering from Hodgkin’s lymphoma, lung cancer, and bladder cancer. Vinblastine works by entering cancer cells and binding to tubulin, which is a protein that forms microtubules. Once Vinblastine has bound to tubulin, it inhibits the assembly of microtubules and proper formation of the mitotic spindle. This causes the cell cycle to arrest. a) Identify and explain two phases of the cell cycle most affected by Vinblastine. b) Identify the checkpoint that is most likely responsible for arresting the cell cycle.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Test your knowledge on the various methods of cell signaling in multicellular organisms. This quiz covers topics such as hormone signaling, paracrine communication, and the role of GPCRs. Assess your understanding of how cells communicate and maintain homeostasis.