# Unit 2: Biology A person contains roughly 100 trillion cells - Cells are roughly 20 `μm` (micrometre, 10-6 m), around 250 cells / cm ## Cell Theory 1. All living things are composed of cells 2. Cells are the basic units of living organisms 3. All cells came from pre-existing cells ## Eukaryotic versus Prokaryotic Cells `Prokaryotic cell`: Meaning before/lacking nucleus `Eukaryotic cell`: Means complete nucleus |Factors|Prokaryotic|Eukaryotic| |:-----------|:----------|:---------| |DNA|In nucleoid region|Usually in membrane-bound nucleus| |Size|Usually smaller|Usually larger| |Organelles|Not membrane-bound, smaller|Membrane-bound, more complex| |Organization|Usually singlecelled|Often form multicellular organisms| |Metabolism|May not need oxygen|Usually need oxygen| ## Organelles ### Cell Membrane - Controls what substances **enter/leave** the cell selectively via various receptors/osmosis - Allows **nutrients** to enter - Allows **waste products** to leave (removal of waste) - Surrounds and holds other organelles in cell - Interact with outside chemicals (e.g., hormones) - Transports food and nutrients into the cell ### Nucleus - Is the control center of the cell - Holds deoxyribonucleic acid (DNA) in form of `chromatin` - DNA is a double helix containing genes - `Genes`: any section of DNA that contains a full set of instructions to make either RNA or a protein, **found** in nucleus - `Chromatin`: is DNA **wrapped tightly** in protein - `Chromosomes`: are even more tightly wrapped `chromatin` used in cell division only, formed when `DNA` **condenses** in `mitosis` - Surrounded by a double membrane - Substances enter and exit the nucleus via `nuclear pores`. `Nuclear pores` are holes in the membrane that allow `proteins` and `nucleic acids` into the `cytoplasm` - Messenger RNA (mRNA) is encoded from DNA and sent to `ribosomes` to produce proteins - Humans have ~2 meters of genes per cell per nucleus tightly wrapped ### Nucleolus - Dense region of DNA located in the nucleus - This area of DNA is specially for ribosomal DNA (rDNA), or DNA used to code `ribosomes`, enzymes that assemble proteins - Produce "large" and "small" subunits of `ribosomes`, which either form complete `ribosomes` in `cytosol` or mix with `endoplasmic reticulum`, forming `rough endoplasmic reticulum` (RER) ### Cytoplasm & Cytosol - `Cytosol` is the fluid cells contain - **All organelles** are suspended in `cytosol` - `Cytoplasm` is the `cytosol` along with everything in a cell, excluding the nucleus ## Endoplasmic Reticulum - The endoplasmic reticulum is a network of `tubules` and **flattened sacs** with a *rough* appearance because of the presence of `ribosomes` on the surface - Network of tubules and flattened sacs - **Transports** proteins via cytoskeleton in vesicles ## Specific to Rough ER - Appears "rough" due to the `ribosomes` attached to its outer surface - Located directly adjacent and attached to nucleus - Located next to `Golgi apparatus` - `Ribosomes` in rough ER **synthesize proteins** - Transports synthesized proteins to `Golgi apparatus` for packaging and distribution - About half the cell's proteins are produced here - Folds, fixes and **modifies both newly-created and pre-existing proteins** somewhat like **proof-reading** ## Specific to Smooth ER - **Does not** synthesize proteins - Appears "smooth" due to lack of `ribosomes` - Located directly adjacent and attached to nucleus - Synthesizes lipids (fats, e.g., cholesterol) - **Metabolises** carbohydrates ## Golgi Apparatus - Also known as Golgi body, Golgi complex, etc. - **Receives, modifies and transports** proteins that were produced by the rough ER - **Packages** proteins into `vesicles` and sends them `cell membrane` for export ## Lysosome - Spherical vesicle that containing `enzymes` - **Digests and kills** foreign matter which is then excreted - E.g., white blood cells use lysosomes to kill bacteria then spit it out - **Digests and breaks down** old and unused material/non-functional organelles as needed - If lysosome ruptures everything dies, hence they are known as "suicude sacs" ## Mitochondria - **Singular form is "mitochondrion"** - Contains an inner and outer membrane - Processes glucose + oxygen gas to form carbon dioxide + adenosine triphosphate (ATP) - ATP allows proteins to do things (e.g., spend 1 ATP break 1 molecule) - ATP cannot be stored - ATP is needed for daily function of the cell ## Cytoskeleton - Made of **protein filaments** - **Maintains** and **changes** cell structure, much like a human skeleton + muscular system - Moves cells - Modifies and adjusts cell structure as needed - Chemicals can travel along `cytoskeleton`, e.g., `organelles`, `vesicles`, etc. ## Organelles specific to animal cells 1. Centrioles and centrosomes 2. Lysosomes ### Centrosomes - Made of same protein as `cytoskeleton` - Crucial to mitosis in animal cells - **Create and manipulate spindle fibres** during mitosis in animal cells ### Lysosomes - Explained before. ## Organelles specific to plant cells 1. Cell wall 2. Chloroplast 3. Central Vacuole ### Cell wall - Provides **structure** and prevents **cell rupture** - A more stronger, thicker, rigit version of the `cell membrane` - Made of **cellulose** (type of sugar) - Also present in most bacteria, fungi, and protists - The antibotic **penicillin** works by destroying the cell walls of bacteria, killing it ### Chloroplast - The **solar panel** of the plant cell - Conducts **photosynthesis** - All chlorophyll is located in chloroplasts - Looks green - Parts of the plant that do not photosynthesize do not have chloroplasts ### Central Vacuole - Extremely large, may take up to 90% of volume in cell - Contains water - Maintains `turgor` pressure against cell wall (pushes against cell wall in all directions) - Maintains cell shape and resistance - Plant cells that lack **turgor pressure** (e.g., celery left in fridge) become **flaccid** ## Cell Division ### Purpose ### 1. Reproduction - Single-cellular organisms reproduce via division **asexually** - Multicellular organisms reproduce via combining two germ cells ("sex cells") that contain half the DNA each of two organisms - This is **sexual** ### 2. Growth - Cells have maximum size before transportation of substances within cell becomes **inefficient**, due to **larger cells** decreasing efficiency of `diffusion` - Cells transport chemicals (e.g., nutrients) via `diffusion`, this **limits cell size** - The only way to maintain proper function and get bigger is to **add more cells** ### 3. Repair - **Organisms need to repair cells to stay alive and maintain proper health** - Millions of cells are replaced everyday - Cells naturally die and need to be replaced - e.g., red blood cells, hair cells, skin, injuries, broken bones ### Cell cycle - **Interphase** - Large majority of a cell's time is spent in interphase - **G1**: (normal growth and function), - Prepare for cell divison - **S**: Replication of DNA - **G2**: Replication of organelles - Checkpoints - Cells check various things before progressing through various stages in interphase - Causes of stopping via checkpoints include damaged DNA, not replicated DNA, lack of nutrients for cell growth, and/or signals from other cells - **Mitosis** - Occurs only in eukaryotic cells - P-MAT: Prophase, Metaphase, Anaphase, Telophase - Division of the nucleus - **Cytokinesis** - **cell division** - The parent cell splits into two daughter cells - **G0** - Cell no longer divides ("cell cycle arrest") - Outside of cell cycle ### Mitosis - `Chromatid`: Supercoiled DNA, only visible during mitosis, cannot be read without unwinding, similar to compressed zip file - `Chromosome`: Two identical "sister chromatids" held together in centre by `centromere`, or one sister chromatid after anaphase - `Centromere`: Proteins sticking sister chromatids - PMAT (prophase, metaphase, anaphase, telophase) - Division of the nucleus | Phase | Diagram | Description | | :--- | :--- | :--- | | Prophase | | - Chromatin condenses into two identical `sister chromatids` which condense into `chromosomes`
- Happens to 23 pairs of chromosomes
- Nuclear membrane dissolves
- Centrosomes move to opposite ends (`poles`) of cell, creating `spindle fibres` that begin to attach to `centromeres` in animal cells | | Metaphase | | - Chromosomes line up in centre of cell to ensure they divide evenly
- Everything in prophase has completed (e.g., nuclear membrane has dissolved completely) | | Anaphase | | - Centromeres split, separating sister chromatids
- Sister chromatids are pulled towards opposite sides of cell via shortening spindle fibres
- Sister chromatids are now called `daughter chromomsomes` | | Telophase | | - Effectively opposite of prophase
- Nuclear membranes form across each of the two new nuclei
- Daughter chromosomes unwind into chromatin and are no longer visible
- Nucleolus forms in each nucleus
- Spindle fibres break apart
- **Cytokinesis** usually begins in telophase
- Cells starts to **cleave** (cell centre starts to pinch itself) | ### Cytokinesis - Cell division - Cell splits completely to two daughter cells - In **animal cells**: Cell membrane pulled inward by cytoskeleton - **"Pinches in"** along equator of cell, forming **"cleavage furrow"** - In **plant cells**: Golgi apparatus produces and sends vesicles to centre of plant cell **"cell plate"** to make new cell wall and membrane between daughter cells ## Cell Specialization - `Zygote`: A single-celled organism formed from the fertilization of an egg by a sperm cell, is a totipotent stem cell - A cell's position in the `gastrula` (outer, middle, inner layer) will determine the fate of the cell, or its potiental. - Chemical signals from other cells will also determine activated genes that lead to specialisation - (LOCATION LOCATION LOCATION!) - Specialisation is determined by reading only certain genes ### Stem Cells - **Unspecialized** cells with the potential to become one of several types of cells. - Can either divide to two stem cells or one stem cell and one specialised cell - Specialised cells generally do not divide | Type of Stem Cell | Obtaining | Potential | Pros | Cons | | :--- | :--- | :--- |:--- | :--- | | Totipotent | Morula (16-cell ball) 3-4 days after lab-fertilised zygote | Unlimited | Unlimited potential, does not initiate immune response | Ethical concerns of destroying fertilized embryos | | Pluripotent | Blastocyst (200-300 cell ball) 4-7 days after fertilisation | Nearly unlimited | Nearly unlimited potential, no need to create new embryo as most are taken from discarded in vitro fertilisation | Ethical concerns of destroying embryos, greater chance of initiating immune response | | Multipotent | Adult stem cells | Limited to cells of their group/organ/location (e.g., blood stem cells to red blood cells, white blood cells, etc.) | Easy to harvest, easy to find | Immune response, limited potential | | Induced pluripotent | Multipotent stem cells | Reprogramming multipotent stem cells using embryonic genes using a virus | Same as pluripotent | Does not require new embryos, immune response not expected, high potential | Technology not there yet to make this possible | ### Potential uses of stem cells - Studying cell growth and function - Testing drugs on specific target cells - Lab-grown meat for vegetarian purposes - Regenerative medicine to replace tissues (e.g., blindness, bone marrow transplant, cancers, limb regrowth) ## Telomeres ## Cancer - Group of diseases that involve out-of-control cell division which may spread throughout the body - `Tumour`: Uncontrolled lump of cells that do not perform normal cellular functions - `Benign`: Describing a tumour that does not metastasise or interfere with normal cell function (harmless, non-cancerous) - `Malignant`: Describing a tumour that does interfere with normal cell activity and metastasise - `Carcinoma`: Cancerous/cancer - `Metastasis`: Primary (original) tumour spreading throughout the body to create secondary tumours - `Carcinogens`: Anything that can cause cancer, e.g., chemicals, radiation/energy, some viruses - `Neoplasm`: A solid or fluid-filled sac that is formed by uncontrolled cell growth (e.g., tumours) - Random mutations can also lead to a cancer cell due to irregular DNA replication - Generally, multiple mutations in several key genes are required for a cell to become cancerous - Cancer is *not* contagious, neither can it be inherited - A genetic predisposition to cancer *can* be inherited - By the time cancer is detected, it can contain millions of cells that have been growing for years ### Cancer screening - PAP smear for cervical cancer - Mammogram for breast cancer - Colonoscopy for colorectal cancer - PSA blood test for prostate cancer ### Cancer diagnosis - Endoscopy (using a flexible camera with tissue extractor to search for cancers of the respiratory and/or digestive systems) - X-rays - Ultrasounds for soft tissues - CAT/CT scan (more x-rays) - MRI scan (uses radio waves and magnetic fields) ### Cancer treatments - Surgery - Physically removing tumour with stabby things - Ineffective if cancer has metastasised - If even one cell escapes the stabby cancer can regrow - Radiation therapy - Blasting radiation at tumours so that their DNA becomes so damaged that DNA replication, and, as a result, cell division is impossible - Can harm neighbouring cells - Ineffective if cancer has metastasised - Chemotherapy - Blasting drugs that kill dividing cells - Does not feel very good for the patient - Fast-growing cells may die off (e.g., hair, skin cells) - Biophonics - Using light beams to detect and treat cancer ## Organ systems **Business model for organ/organ systems** | Business thing | Corresponding organ/organ system | | :--- | :--- | | Management | Central nervous system (brain) | | Messaging | Endocrine + peripheral nervous systems | | Workplace | Body | | Transport | Circulatory, digestive, urinary systems (internal, import, export, respectively) | | Storage | Fats | | Cash flow | Digestive + respiratory systems | | Security | Immune + integumentary (skin) systems | | Workers | Cells + muscular system | ## Tissues - `Tissues`: Different cell types grouped together performing the same task - Organisms have a hierarchical organisation - Basic tissues: Connective, muscle, nervous, and epithelial tissues - Epithelial tissue - Tightly packed cells that line body surfaces, e.g., skin - Connective tissue - Produces collagen fibres that support organ structures and bone, e.g., ligaments (bone -> bone), tendons (muscle -> bone) - Muscle tissue - Fibrous tissue that can be subdivided into cardiac (heart), smooth (digestive), and skeletal (voluntary) muscle tissues - They contract - Nervous tissue - Responds to external/internal stimuli, e.g., brain, nerves ## Digestive system - Two types of digestive systems - Bag digestive system - One way in, same way out (e.g., coral, jellyfish) - Tube digestive system - One way in, another way out (e.g., worms, humans) - Mouth -> esophagus -> stomach -> small intestine -> large intestine -> rectum -> anus all part of the tube - Gallbladder, liver, salivary glands, and pancreas produce digestive enzymes/juices in humans - Process of eating food: **Ingestion** (eat) -> **digestion** (physical and chemical breakdown) -> **absorption** (of nutrients to bloodstream) -> **egestion** (poo) - Flies digest before ingesting - `Jujunum`: Centre of small intestine - `Duodenum`: Beginning of small intestine - `Ileum`: End of small intestine - `Rectum`: Holds waste to be excreted voluntarily - `Anus`: Controls waste to be defecated voluntarily - `Appendix`: Used to be used to digest plant matter, now virtually useless in humans - `Gallbladder`: Stores and secretes bile as buffer between liver and small intestine that helps break down fats (lipids) - `Ruminants`: Herbivores that digest food using a chambered tube - Chew -> Reticulum and rumen (first and second stomachs) -> regurgitate and rechew -> Omasum (third stomach) -> Abomasum (fourth stomach) -> small intestine -> large intestine -> waste - `Eoprophagy`: Consumption of feces ### Human digestive system - Mouth ingests food - Teeth, tongue, and salivary glands work to begin digestion - Esophagus squeezes food down in waves (peristalsis) down its smooth muscle tube - Stomach - Mixes hydrochloric acid with digestive enzymes to break down food - Hydrochloric acid is diluted and does not break down the food itself much, enzymes are more effective at a lower pH - Liquifies food and kills bacteria - **Goblet cells** produce **mucous**, which lubricates the stomach and intestines, protecting the stomach - Made of smooth muscle to churn food, somewhat like cooking with enzymes or a washing machine - Intestines - Pancreas makes most digestive enzymes and pumps them in the duodenum - Absorbs nutrients and water to bloodstream - Forms and excretes feces - Contains smooth muscle to continue peristalsis - Contains plenty of blood vessels for faster nutrient absorption - Intestinal epithelium - Optimised for surface area - Folds contain `villi` (singular, "villus") - Villi contain capillaries and absorbing and goblet cells - Absorbing cells caintain microvilli, which absorb nutrients via diffusion ## Respiratory system - Exchanges oxygen gas and carbon dioxide gas between red blood cells and the surrounding air, which is required for cellular respiration - Diaphragm contracts to lower itself, causing the rib cage to rise, which increases lung volume, which subsequently causes pressure to decrease and air to rush in to the lungs - Diaphragm relaxes to return everything to its normal position - Air is warmed and moisted while passing through nasal cavity blood vessels - Trachea and bronchi are made of rigid cartilage rings - Prevents airways from closing, similar to a vacuum hose - Respiratory epithelium - Contains goblet and ciliated cells - `Cilia`: Singular "cilius", sweep mucous out of the lungs and throat - Nose hairs and mucous trap debris which is swept out by cilia - Alveoli (singular "alveolus") epithelial tissue is one cell thick - Surrounded with capillaries which exchange gases via diffusion - Trachea -> 2 bronchi -> bronchioles -> alveoli - Gas exchange - Swapping of carbon dioxide and oxygen gas between the bloodstream and the environment (e.g., red blood cells and alveoli) - A large surface area, thin membrane, and moisture are all required for optimal gas exchange - Alternate gas exchange systems include - Fish using a constant water flow forcing dissolved oxygen through their gills - Gills stick together out of water, resulting in suffocation - Frogs use lungs on land, but can also perform gas exchange underwater using their skin ## Circulatory system - Interacts with literally every other system - Carries oxygen and nutrients to cells, carries carbon dioxide and waste away ### Components - Composed of heart, arteries, veins, and capillaries - `Arteries` flow **away** from the heart - Made of **thick** muscle layers and elastic connective tissue - Muscle layers must withstand and **maintain** higher blood pressure throughout body due to proximity to heart - May `vasoconstrict` or `vasodilate` to increase or restrict blood flow, for example, to blush or to pale, respectively - `Veins` flow **to** the heart - Made of **thin** muscle layers and elastic connective tissue - Carries low pressure blood with valves to ensure one-way flow - Blood moves by movement of skeletal muscles pushing blood - `Capillaries` are one cell thick - They transition between arteries and veins - Blood cells are forced to go in single file - Present, amongst other places, in alveoli and villi - The `heart` pumps blood throughout the body - Has one-way valves - Has four chambers, two `atria` (sing. `atrium`) and two `ventricles` - Blood is returned to atria which push them to ventricles which push them out of the heart - **Right** side of heart receives and sends **deoxygenated** blood **to** lungs - **Left** side of heart receives and sends **oxygenated** blood **from** lungs - Invertebrate circulatory systems are either **open** or **closed** (douse everything with blood then collect or use vessels like we do, respectively) - Most invertebrates have an open circulatory system ### Myocardial infarction - Also known as **heart attack** - When `atherosclerosis` occurs in `coronary arteries` (when fatty plaque deposits build up in arteries feeding the heart) - If clots break open a larger clot forms over it - This repeats until the artery is completely blocked, leading to death of cardiac muscle cells - Caused by lifestyle choices, although predisposition can be increased due to genes ### Blood - Composed of red blood cells, white blood cells, platelets, and plasma - `Red blood cells`: Biconcave discs carrying oxygen and carbon dioxide to and from cells, respectively, using `hemoglobin` - Denucleated, instead packing as much hemoglobin as possible inside - Hemoglobin and oxygen give them their colour - `White blood cells`: Part of the immune system, they neutralise and remove foreign threats - Can make antibodies - Can engulf and kill pathogens - 700:1 ratio of red blood cells to white blood cells - `Plasma`: Clear fluid made of 90% water filled with proteins and dissolved nutrients - `Platelets`: Irregular colourless "bodies" that form **fibrous** clots ## Immune system - `Pathogens`: any**thing** that cause disease - Pathogen waste can be toxic which cause symptoms of disease - Passive defense - Skin - physical barrier - Sweat/tears - `lysozymes` kill bacteria - Stomach acid - it's acid dangit acid kills things - Beneficial bacteria overpopulate surfaces to prevent harmful bacteria from settling - Adaptive defense - `White blood cells`: For the sake of G10, divided into two subtypes: - Cells that engulf and consume bodies (`phagocytes`, e.g., macrophages) - Cells that produce antibodies (`plasma B cells`, i.e., plasma B cells) - `Antibodies`: Secreted proteins that stick to a specific molecule found on pathogens - Clumps pathogens together for simple cleanup and prevents them from spreading - Covers and prevents toxins from reacting - Acts as a flag for phagocytes to destroy marked pathogen or toxin - Acquired immunity - After initial immune response, antibodies are still produced for that type of pathogen - Once pathogen is detected again, "memory cells" reactivate and kill things faster - Much faster than initial response, typically resulting in no symptoms - This is why you generally can never be sick from the same pathogen twice - Pathogens mutate (e.g., influenza) so that they are no longer recognisable by antibodies - `Vaccination`: Injecting a small amount of a **dead/weakened** version of pathogen giving acquired immunity without actually getting disease - There may be mild side effects - `Boosters` are required for some vaccines as "memory" fades over time (e.g., tetanus) - `Herd immunity`: When enough of the population (90% in general) is immune to a disease, drastically reducing rate of disease even amongst those not immune - Those who cannot be vaccinated for whatever reason are protected due to a far lower chance of encountering the disease itself - Prevention (vaccine) > cure (treatment) - Chance of disease from the vaccine are far lower than chance of death or serious infection from a pathogen - Vaccines do not cause autism or seizures, but may act as a trigger for the latter due to genetics ## Musculoskeletal system - Maintains **structure** - **Protects** other systems and cells - Enables **movement** - Four types of **connective tissues**: Ligaments, tendons, bones, and cartilage | **Bone** | **Information** | **Location** | | :--- | :--- | :--- | | Clavicle | Collarbone | Collar | | Humerus | Funny bone | Lower upper arm | | Femur | Largest bone | Thigh | | Tibia | One of two bones in lower leg | Front lower leg | | Vertebrae | Enable spinal movement | Spine | | Patella | Prevents leg overextension and protects knee join | Kneecap | ### Bones - Hard and dense - Bone cells produce minerals (e.g., phosphorus + calcuium) and **collagen** - Minerals for strength, collagen for flexibility - Bone marrow produces blood cells - Contain blood cells ### Joints - Anywhere where two bones meet - Types of joints - Hinge joint (e.g., knee, elbow) - Ball and socket joint (e.g., Hip, shoulder) - Fixed (e.g., skull, pelvis) - `Ligaments` connect bones across joints - `Cartilage` cushions bone on each side of joint and allows for smooth motion ### Skeletal Muscle - Made of **striated** muscle fibres of long cells - Voluntary muscles, receive signals from brain via nerves - Always come in pairs as **any muscle can only pull, not push** - Must be attached to two bones in order to move a bone ## Nervous System - Coordinates body activities - `Central nervous system`: Brain + spinal cord - `Peripheral nervous system`: All other nerves connecting everything to spinal cord/brain - `Neurons` send electric signals down their singular long `axon` branch thing - They accept signals from `dendrites` on the main cell body - `Schwann cells` form the `myelin sheath` to insulate and nurture the axon, protecting it from interference - Neurotransmitters are chemical signals that transmit information between neurons - Electrical signals tell chemical signals to go to other neurons - Nerves - Bundle of axons - Surrounded with blood vessels and connective tissue - Nerve signals are short-lived, fast, and targeted towards specific groups of cells ### Disorders - Parkinson's disease - Loss of brain neurons that send neurotransmitters to muscles - Leads to muscular and mental decline - Multiple sclerosis - Immune system attacks myelin sheath - Disruption of neurons' electric signals due to lack of protection - Causes spasms and loss of muscular control - Alzheimer's disease - Protein deposits (plaque) build up in brain tissue - Leads to memory loss and total system failure ## Endocrine System - Coordinates organ functions - `Hormone` chemical signals produced by endocrine glands that, compared to nerve signals, are **long-lasting**, **slower**, and **general** - Specific hormones bind to specific receptors on specific cell membranes (e.g., mailing lists) - Hormones travel through the bloodstream - Hormones either encourage or discourage activity - Can cause positive or negative feedback loops with glands | **Endocrine organ** | **Purpose** | **Location** | | :--- | :--- | :--- | | Pituitary gland | Controls growth and development | Brain | | Pancreas | Secretes insulin to ensure sugar in bloodstream is taken in by cells | Attached to duodenum | | Gonads (ovaries + testes) | Secretes the reproductive hormones testosterone and estrogen, respectively | Lower abdomen | | Adrenal glands | Control stress response, secrete adrenaline (fight/flight response) | Above kidneys | ### Disorders - Type 1 diabetes: The pancreas is unable to produce any insulin, resulting in high blood sugar - Generally caused by genetics - Type 2 diabetes: The pancreas produces not enough insulin and/or cells are resistant to it, resulting in high blood sugar - Generally caused by lifestyle choices (e.g., diet) - Growth disorders (dwarfism/gigantism) - Caused by poor pituitary and/or hypothalamus function or endocrine gland damage as an adult