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October, 2006
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Death: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.

Life Histories

JoVE 10941

Constrained by limited energy and resources, organisms must compromise between offspring quantity and parental investment. This trade-off is represented by two primary reproductive strategies; K-strategists produce few offspring but provide substantial parental support, whereas r-strategists produce much progeny that receives little care. These strategies are related to an organism’s survival likelihood across its lifespan, which is represented by a survivorship curve. Three general types of survivorship curves are exhibited by organisms that: tend to live long lives (Type I, K-strategists); are equally likely to die at all ages (Type II); or have high early mortality rates, but long lifespans if they survive into adulthood (Type III, r-strategists). An organism’s life history includes all the events occurring across its lifespan, including birth, development, sexual maturation, reproduction, and death. Trade-offs involving the patterns and timing of life history events (notably survival and reproduction) across different ages and developmental stages represent different life history strategies. R-strategists and K-strategists make distinct reproductive compromises between the number of offspring and level of parental care, or offspring quantity versus quality. R-strategists (r

 Core: Biology


JoVE 10902

In response to tissue injury and infection, mast cells initiate inflammation. Mast cells release chemicals that increase the permeability of adjacent blood capillaries and attract additional immune cells to the wound or site of infection. Neutrophils are phagocytic leukocytes that exit the bloodstream and engulf invading microbes. Blood clotting platelets seal the wound and fibers create a scaffold for wound healing. Macrophages engulf aging neutrophils to end the acute inflammatory response. Tissue injury and infection are the primary causes of acute inflammation. Inflammation protects the body by eliminating the cause of tissue injury and initiating the removal of cell debris resulting from the initial damage and related immune cell activity. Inflammation involves mediators of both the innate and adaptive immune system. Proper regulation of inflammation is crucial to clear the pathogen and remove cell debris without overly damaging healthy tissue in the process. If inflammatory processes are not properly regulated, chronic inflammation can arise that is often fatal. Mast cells are the first to respond to tissue injury, as they are primarily located in areas that have contact with the exterior: the skin, gut, and airways. Mast cells have an arsenal of receptors on their cell surface and can hence be activated by a wide variety of stimuli, such as mi

 Core: Biology

Anatomy of the Heart

JoVE 10886

The human heart is made up of three layers of tissue that are surrounded by the pericardium, a membrane that protects and confines the heart. The outermost layer, closest to the pericardium, is the epicardium. The pericardial cavity separates the pericardium from the epicardium. Beneath the epicardium is the myocardium, the middle layer, and the endocardium, the innermost layer. There are four chambers of the heart: the right atrium, the right ventricle, the left atrium, and the left ventricle. These compartments have two types of valves—atrioventricular and semilunar—that prevent blood from flowing in the wrong direction. The right atrium receives blood from the coronary sinus and the superior and inferior vena cavae. This blood goes into the right ventricle via the right atrioventricular (or tricuspid) valve, a flap of connective tissue that prevents the backflow of blood into the atrium. Then, the blood leaves the heart, traveling through the pulmonary semilunar valve into the pulmonary artery. Blood is then carried back into the left atrium of the heart by the pulmonary veins. Between the left atrium and the left ventricle, the blood is again passed through an atrioventricular valve that prevents backflow into the atrium. This atrioventricular valve is called the bicuspid (or mitral) valve. The blood passes through the left ventricle into the aorta

 Core: Biology

RNA Splicing

JoVE 10802

The process in which eukaryotic RNA is edited prior to protein translation is called splicing. It removes regions that do not code for proteins and patches the protein-coding regions together. Splicing also allows several protein variants to be expressed from a single gene and plays an essential role in development, tissue differentiation, and adaptation to environmental stress. Errors in splicing can lead to diseases such as cancer. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts designated to become mRNA are called precursor messenger RNA (pre-mRNA). The pre-mRNA is then processed to form mature mRNA that is suitable for protein translation. Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins whereas introns are the non-coding regions. RNA splicing is the process by which introns are removed and exons patched together. Splicing is mediated by the spliceosome—a complex of proteins and RNA called small nuclear ribonucleoproteins (snRNPs). The spliceosome recognizes specific nucleotide sequences at exon/intron boundaries. First, it binds to a GU-containing sequence at the 5’ end of the intron and to a branch point sequence containing an A towards the 3’ end of the intron. In a number of carefully-orches

 Core: Biology

Nucleotide Excision Repair

JoVE 10792

Exposure to mutagens can damage DNA and result in bulky lesions that distort the double-helix structure or impede proper transcription. Damaged DNA can be detected and repaired in a process called nucleotide excision repair (NER). NER employs a set of specialized proteins that first scan DNA to detect a damaged region. Next, NER proteins separate the strands and excise the damaged area. Finally, they coordinate the replacement with new, matching nucleotides. Cells are regularly exposed to mutagens—factors in the environment which can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes to DNA. These include bends or kinks in the structure which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations which in turn can result in cancer or disease depending on which sequences are disrupted. Nucleotide excision repair relies on specific protein complexes to recognize damaged regions of DNA and flag them for removal and repair. In prokaryotes, the process involves three proteins—UvrA, UvrB, and UvrC. The first two proteins work together as a complex, traveling along the DNA strands to detect any physical aberrations. Once identified, the strands at the damaged location are separated, and endon

 Core: Biology

What is the Cell Cycle?

JoVE 10757

The cell cycle refers to the sequence of events occurring throughout a typical cell’s life. In eukaryotic cells, the somatic cell cycle has two stages: interphase and the mitotic phase. During interphase, the cell grows, performs its basic metabolic functions, copies its DNA, and prepares for mitotic cell division. Then, during mitosis and cytokinesis, the cell divides its nuclear and cytoplasmic materials, respectively. This generates two daughter cells that are identical to the original parent cell. The cell cycle is essential for the growth of the organism, replacement of damaged cells, and regeneration of aged cells. Cancer is the result of uncontrolled cell division sparked by a gene mutation. There are three major checkpoints in the eukaryotic cell cycle. At each checkpoint, the progression to the next cell cycle stage can be halted until conditions are more favorable. The G1 checkpoint is the first of these, where a cell’s size, energy, nutrients, DNA quality, and other external factors are evaluated. If the cell is deemed inadequate, it does not continue to the S phase of interphase. The G2 checkpoint is the second checkpoint. Here, the cell ensures that all of the DNA has been replicated and is not damaged before entering mitosis. If any DNA damage is detected that cannot be repaired, the cell may undergo apoptosis, or

 Core: Biology


JoVE 10733

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.

During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly phosphorylated amino acids. Accordingly, protein kinases are classified as serine/threonine kinases, tyrosine kinases, or dual action kinases if they can phosphorylate all three amino acids. Conversely, protein phosphatases catalyze the removal of the phosphate group (dephosphorylation), restoring the original properties of the protein. Under physiological conditions, phosphorylation and dephosphorylation are tightly regulated to prevent prolonged changes in protein structure and function. Disruption of this balance can cause diseases, including cancer and various neurodegenerative disorders. For instance, a protein called tau is hyperphosphorylated in Alzheimer’s disease (AD). Physiologically, tau regulates the shape, structure, and development of neurons. The tau protein contains over 80 serine, threonine, and tyrosine residues, of which only a fraction is usually pho

 Core: Biology

Contact-dependent Signaling

JoVE 10715

Contact-dependent signaling uses specialized cytoplasmic channels between cells that allow the flow of small molecules between them. In animal cells, these channels are called gap junctions. In plants, they are known as plasmodesmata.

Gap junctions form when two hemichannels, or connexons, join; one connexon from one cell coupling to a connexon of an adjacent cell. Each cell’s connexon is formed from six proteins creating a circular channel. There are over 20 different types of these proteins, or connexins, so there is substantial variation in how they come together as connexons and as gap junctions. Connexins have four transmembrane subunits with both their N- and C-terminus endings located intracellularly. The C-terminus has multiple phosphorylation sites so it can be activated by numerous different kinases- further adding to gap junction variety. Depending on the activating kinase, and the C-terminal amino acid residues of connexins that are phosphorylated, gap junctions can be partially or fully opened. This selectively allows small molecules to flow from one cell into another. A gap junction may also exclude by electrochemical charge. The selectivity of gap junctions allows a single cell to coordinate a complex multicellular response. However, some toxic molecules, matching the size and electrochemical preference of the gap junction, can also p

 Core: Biology

Yeast Signaling

JoVE 10714

Yeasts are single-celled organisms, but unlike bacteria, they are eukaryotes—cells that have a nucleus. Cell signaling in yeast is similar to signaling in other eukaryotic cells. A ligand, such as a protein or a small molecule outside the yeast cell, attaches to a receptor on the cell surface. The binding stimulates second-messenger kinases (enzymes that phosphorylate specific substrates) to activate or inactivate transcription factors that regulate gene expression. Many of the yeast intracellular signaling cascades have similar counterparts in Homo sapiens, making yeast a convenient model for studying intracellular signaling in humans. Yeasts are members of the fungus kingdom. They use signaling for various functions, especially for reproduction. Yeasts can undergo “sexual” reproduction using mating pheromones, which are peptides—short chains of amino acids. Yeast colonies consist of both diploid and haploid cells. Both types of cells can undergo mitosis, but only diploid cells can undergo meiosis. When diploid cells undergo meiosis, the four resulting haploid cells, called spores, are not identical. In fact, the division of one diploid cell into four spores creates two “sexes” of yeast cells, each two cells of the type MAT-a and MAT-alpha. MAT-a cells secrete mating

 Core: Biology

Ionic Bonds

JoVE 10665

When atoms gain or lose electrons to achieve a more stable electron configuration they form ions. Ionic bonds are electrostatic attractions between ions with opposite charges. Ionic compounds are rigid and brittle when solid and may dissociate into their constituent ions in water. Covalent compounds, by contrast, remain intact unless a chemical reaction breaks them.

Ionic bonds are reversible electrostatic interactions between ions with opposing charges. Elements that are the most reactive (i.e., have a higher tendency to undergo chemical reactions) include those that only have one valence electron, (e.g., potassium) and those that need one more valence electron (e.g., chlorine). Ions that lose electrons have a positive charge and are referred to as cations. Ions that gain electrons have a negative charge and are called anions. Cations and anions combine in ratios that result in a net charge of 0 for the compound they form. For example, the compound potassium chloride (KCl) contains one chloride ion for each potassium ion, because the charge of potassium is +1 and the charge of chloride is -1. The compound magnesium chloride (MgCl2) contains two chloride ions for each magnesium ion because magnesium’s charge is +2. The electrostatic forces holding ionic compounds together are strong when the compounds are in solid form. Since t

 Core: Biology
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