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Showing posts with the label Cell Death and Renewal

Briefly explain how BCI-2 and MCL-1 inhibitors help in cancer treatment. Give examples (two each) of BCI-2 and MCL-1 inhibitors

Bcl-2 and Mcl-1 are  anti-apoptotic proteins  that belong to the  Bcl-2 family,  which controls the process of programmed cell death or apoptosis. In many types of cancers, these proteins are found in high levels. Because of this, the cancer cells avoid apoptosis, even when they are damaged or abnormal. This helps the cancer cells survive for a long time, grow uncontrollably and become resistant to chemotherapy or radiation. To stop this abnormal survival of cancer cells, scientists have developed special drugs called  Bcl-2 inhibitors and Mcl-1 inhibitors.  Bcl-2 and Mcl-1 inhibitors are special drugs that  block the action of these anti-apoptotic proteins.  When these proteins are blocked, the cancer cells lose their ability to avoid apoptosis. As a result, the natural process of cell death restarts. These inhibitors allow the pro-apoptotic proteins (like Bax and Bak) to become active again, which helps in triggering the death of cancer cells. B...
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What are the different sub-classes of BCI2 proteins? Explain briefly based on structure and function

The Bcl-2 family of proteins is a very important group of regulatory proteins that play a major role in the intrinsic (mitochondrial) pathway of apoptosis, which is a kind of programmed cell death. These proteins mainly control the permeability of the mitochondrial outer membrane and thus regulate the release of  apoptotic factors  like  cytochrome c.  This family includes both pro-apoptotic proteins (which promote cell death) and anti-apoptotic proteins (which protect the cell from dying). Sub-classes of Bcl-2 Family Proteins These proteins are classified into different sub-classes based on the number and type of BH (Bcl-2 Homology) domains they contain, and also based on their functional role in apoptosis. There are three major sub-classes of Bcl-2 family proteins. 1. Anti-apoptotic Bcl-2 Proteins (BH1-BH4 containing proteins) These proteins inhibit apoptosis and protect cells from death. Structurally, they have  all four BH domains: BH1, BH2, BH3 and BH4. ...
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What are the initiator and effector caspases? Give examples of each

Caspases are a special family of  protease enzymes  that play a very important role in apoptosis, which is also known as  programmed cell death.  These enzymes are present in an inactive form inside the cell and get activated when the cell receives a signal to die. Caspases work like a chain reaction. Some caspases get activated first and then they activate other caspases. Based on their function in the apoptosis process, caspases are mainly divided into two groups:  initiator caspases and effector caspases.  Both types work together to ensure proper and controlled death of damaged or unnecessary cells in the body. 1. Initiator Caspases: Initiator caspases are the  first enzymes  to be activated when the cell receives a death signal. These caspases act like a starting point in the apoptotic pathway. They do not break down the cell directly but instead activate other caspases (effector caspases) by cutting them at specific places. Initiator caspase...
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Name any two each of fluorescent and non-fluorescent stains to measure cell death

To measure cell death in cells, scientists use special types of chemical dyes called  stains.  These stains help to identify whether the cells are alive, dead, or undergoing a specific type of death like apoptosis or necrosis. These stains can be broadly divided into two types based on their properties:  fluorescent stains  and  non-fluorescent stains. 1. Fluorescent Stains Fluorescent stains emit visible light (usually green, red and blue) when exposed to specific wavelengths of light under a fluorescence microscope. These stains are commonly used in cell biology and molecular biology labs to identify apoptotic and necrotic cells by detecting changes in their membranes or internal cell structures. Examples of fluorescent stains: 1. Propidium Iodide (PI): This dye is impermeable to live cells but easily enters dead or damaged cells due to their leaky plasma membrane. Once inside, it binds strongly to DNA and gives a  bright red fluorescence.  It is esp...
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What is the principle of LDH assay for the measurement of cell death?

LDH assay is one of the most commonly used biochemical methods to measure cell membrane damage and cell death, especially during necrosis or late-stage apoptosis. LDH stands for  Lactate Dehydrogenase,  which is an intracellular enzyme found in the cytoplasm of almost all cells. Under normal conditions, LDH remains inside the cell. But when the cell membrane becomes damaged or ruptured due to stress, toxin, or cell death, LDH leaks out into the surrounding medium. The LDH assay takes advantage of this leakage to estimate the extent of cell death. Principle of the LDH Assay The principle of the LDH assay is based on the ability of LDH enzyme to catalyze a reaction that changes  lactate to pyruvate.  This reaction also results in the conversion of  NAD⁺ to NADH.  The NADH produced can then react with specific substrates to create a colored product, which can be measured using a  spectrophotometer. The overall reaction looks like this: Lactate + NAD⁺ → Py...
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What are the major stages of autophagy?

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Autophagy is a highly regulated catabolic process in which cells degrade and recycle their own components like damaged organelles, misfolded proteins or excess cytoplasmic material. The word  "autophagy"  means  "self-eating"  and it is important for maintaining cellular health, especially during stress, starvation or damage. The process is controlled by  autophagy-related genes (ATG)  and it plays a crucial role in cell survival, immunity, aging and disease regulation. There are different types of autophagy, but the most studied and important one is macroautophagy, commonly referred to simply as autophagy. Major Stages of Autophagy Autophagy does not occur randomly, but in an orderly step-wise manner. There are five major stages of autophagy and each stage is controlled by specific proteins and molecular signals. 1. Initiation (Induction) In this first step, autophagy is triggered by signals such as nutrient deprivation, oxidative stress and damage. These ...
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Indicate the difference between intrinsic and extrinsic apoptotic pathways

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Apoptosis  is a highly regulated process of  programmed cell death  that removes unwanted or damaged cells without causing inflammation. There are two main apoptotic pathways: the  intrinsic (mitochondrial) pathway  and  the extrinsic (death receptor) pathway.  The  intrinsic pathway  is triggered by internal stress like DNA damage, while the  extrinsic pathway  is activated by external signals such as death ligands. Even though both pathways lead to programmed cell death, they are quite different in many ways. These differences are based on various criteria such as: 1. Based on Type of Triggering Signal Intrinsic pathway  is activated by  internal cellular stress signals  such as DNA damage, oxidative stress and ER stress. These arise from within the cell itself, usually due to damage or malfunction that threatens cell survival. Extrinsic pathway  is triggered by  external signals  like binding of deat...
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Differentiate between necrosis and apoptosis

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Necrosis and apoptosis are two different types of cell death. Both occur in different situations and have different effects on cells and tissues. Here are the differences  between necrosis and apoptosis bssed on different key criteria: 1. Based on Process Type and Regulation Necrosis  is an  uncontrolled,  passive and pathological type of cell death. It happens when a cell is injured suddenly due to harmful external factors like infection, mechanical trauma, or loss of blood supply. The cell does not participate in its own death. Apoptosis,  on the other hand, is a highly  regulated and controlled  physiological process. It is also called programmed cell death. Here, the cell itself activates a sequence of steps to die in a clean and safe way, especially during development or when it becomes damaged. 2. Based on Morphological Changes in Cell In necrosis,  the cell swells, organelles also swell and finally the plasma membrane breaks. This leads to ...
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What are necrostatins?

In normal conditions, cells die in a controlled way through  apoptosis,  which is a peaceful and clean process that does not harm nearby tissues. But sometimes, when apoptosis is blocked or does not work properly, the body uses another backup method to kill the damaged or infected cell. This second method is called  necroptosis.  Necroptosis is a form of programmed cell death, but unlike apoptosis, it causes the cell to swell, burst and release harmful substances, which leads to inflammation and tissue damage. Necrostatins  are a group of s mall synthetic chemical molecules  that are used to block  necroptosis,  which is a type of programmed cell death. They work by stopping the activity of a key protein called  RIPK1 (Receptor Interacting Protein Kinase 1).  This protein is very important for starting the necroptosis process. If RIPK1 is blocked, then necroptosis cannot happen. The first necrostatin that was discovered is called  N...
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What are BH domains? What is their importance in apoptosis?

BH domains or Bcl-2 Homology domains, are conserved amino acid sequence regions found in the members of the  Bcl-2 family of proteins,  which play an essential role in regulating apoptosis, especially in the intrinsic mitochondrial pathway. The term "BH" comes from the first discovered member of this family, Bcl-2 (B-cell lymphoma 2). These domains help in  protein-protein interactions  that either promote or prevent apoptosis, depending on the type of protein in which they are present. These BH domains are very important because they determine the pro-apoptotic or anti-apoptotic nature of the Bcl-2 family proteins. Some proteins, like Bcl-2 and Bcl-xL, help the cell survive by blocking apoptosis. Others, like Bax, Bak and Bid, help in killing the cell by starting the apoptotic process. The BH domains control these actions. Types of BH Domains There are four types of BH (Bcl-2 homology) domains and each one plays a different role in the process of apoptosis. 1. BH1 D...
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Name the components of an apoptosome and a necrosome. What is the difference in the function of an apoptosome and a necrosome?

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In the cell, programmed forms of death are controlled by special protein complexes. Two important complexes among them are the  apoptosome,  which helps in the process of  apoptosis,  and the  necrosome,  which is involved in  necroptosis.  Though both are connected with cell death, their components are different and they function through separate pathways. Components of the Apoptosome: The apoptosome is a large protein complex that plays a crucial role in the intrinsic pathway of apoptosis. It forms when  mitochondrial outer membrane permeabilization (MOMP)  occurs, leading to the release of various mitochondrial factors into the cytosol. The main components of the apoptosome are: Cytochrome c:  Released from the mitochondria into the cytosol during MOMP. It plays a key role in activating the apoptosome. Apaf-1 (Apoptotic protease-activating factor 1):  A cytosolic protein that binds to cytochrome c and undergoes a conformatio...
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How do pro-apoptotic proteins differ from pro-survival proteins? Give examples (two each) for both classes of proteins mentioned

In the intrinsic pathway of apoptosis, a special group of proteins called the  Bcl-2 family  plays a major role in controlling whether the cell will live or die. This family has two opposite types of proteins. First type is called  pro-apoptotic proteins,  which promote cell death. Second type is called  pro-survival proteins,  which protect the cell and stop it from dying. These pro-survival proteins are also called  anti-apoptotic proteins,  because their function is to stop apoptosis. These two groups work by controlling a key event called  mitochondrial outer membrane permeabilization (MOMP).  If pro-apoptotic proteins win, then MOMP happens and apoptosis starts. But if pro-survival proteins are stronger, then MOMP is blocked and the cell survives. Pro-apoptotic proteins These proteins promote  apoptosis  by causing damage to the outer mitochondrial membrane. They help in a critical step called mitochondrial outer membrane ...
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What is mitochondrial outer membrane permeabilization (MOMP)? How is it important in the process of apoptosis?

Mitochondrial outer membrane permeabilization (MOMP)  is an essential and highly regulated step in the  intrinsic pathway of apoptosis,  which refers to the programmed and controlled death of a cell. In this process, the outer membrane of the mitochondria becomes  permeable,  meaning it develops openings or pores. As a result, certain proteins that are usually stored safely inside the mitochondrial intermembrane space get released into the  cytoplasm.  These released proteins serve as strong intracellular signals that trigger a cascade of events leading the cell towards apoptosis. Thus, MOMP acts as a critical checkpoint in deciding whether a cell will survive or enter the death pathway. MOMP does not happen suddenly or accidentally. It is highly regulated by a group of proteins known as the  Bcl-2 family.  This family includes both  pro-apoptotic proteins  and  anti-apoptotic proteins. The pro-apoptotic proteins  members ...
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What are autophagosomes and autolysosomes? Indicate the major difference between the two

Inside eukaryotic cells, there is a special self-cleaning process known as  autophagy.  This process helps the cell to remove its own damaged organelles, misfolded proteins, or other unwanted cytoplasmic materials. It is especially active during stress, starvation and low energy conditions. Autophagy allows the cell to recycle these unwanted components and use them again for energy or rebuilding. During this pathway, the cell forms two important vesicle-like structures at two different stages of the process:  autophagosome  and  autolysosome.  These two structures work one after the other to complete the cleaning and recycling task. Autophagosome An autophagosome is a  double-membrane  vesicle that forms during the early stage of autophagy. It begins by surrounding the targeted material, such as damaged mitochondria and protein aggregates. This membrane keeps extending until it completely encloses the selected material, forming a sealed vesicle. A...
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What is the difference between the classical concept and the modern concept of genes?

The concept of the gene has evolved from a simple unit of heredity to a complex molecular entity. During  Mendel's  time, genes were understood only through the inheritance of physical traits. This formed the  classical concept.  With the discovery of DNA, its double helix structure and the development of molecular biology, the gene is now defined by its chemical structure and functional properties. This is known as the  modern concept. For understanding the difference between the classical and modern concept of genes, the following criteria are used: 1. Based on Definition or Concept Classical Concept:  Gene was defined as an abstract unit of heredity responsible for controlling a  single trait.  It was known through breeding experiments and inheritance patterns. Modern Concept:  A gene is a segment of DNA that contains the information to produce a functional product, either a protein or an RNA. It is both a structural and functional unit of...
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Why is the frequency of double crossover overly low?

The frequency of double crossover is usually much lower than expected. This is mainly due to a natural genetic mechanism called interference, which controls the distribution of crossover events during meiosis. Crossover is essential for genetic recombination but is also tightly regulated to prevent instability in the genome. The lower frequency of double crossovers can be explained by the following reasons: 1. Physical Constraints of Chromosomes Chromosomes have a limited length and physical structure. When a crossover happens at one region of a chromosome, the local chromatin structure and spatial arrangement become less favorable for another crossover nearby. This physical limitation reduces the chance of two crossovers occurring very close to each other on the same chromosome segment. 2. Crossover Interference One of the main reasons for reduced double crossovers is the phenomenon called  interference.  Interference is the effect where the occurrence of one crossover decrea...
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What is gene mapping? How do the linked genes help in gene mapping?

Gene mapping is the method used to determine the location of genes on a chromosome and the distance between them. It helps in identifying the exact position of a gene responsible for a particular trait or disease. The concept started with the work of  Thomas Hunt Morgan  in the early 1900s when he studied Drosophila melanogaster (fruit fly) and observed that some traits are inherited together. This was because the genes responsible for those traits were located close to each other on the same chromosome. This phenomenon is known as  linkage. There are two main types of gene mapping: 1. Genetic Mapping (Linkage Mapping): Genetic mapping uses the frequency of recombination or crossing over between genes to estimate their distance on a chromosome. It gives a  relative position of genes rather than their exact physical location. 2. Physical Mapping Physical mapping uses molecular biology techniques to determine the exact nucleotide sequence of DNA and the exact physical ...
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The First Living Molecule

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The question of which molecule can be considered the "first living molecule" is complex and doesn't have a definitive answer. This depends on whether we are discussing the molecule that played a key role in the  origin of life  or the  first organic molecules  that formed chemically on early Earth. While  RNA is considered crucial in the emergence of life,   amino acids were likely the first molecules to appear in Earth's primordial environment.  Understanding these distinctions clarifies the discussion about whether RNA or amino acids came first. Introduction: 1. According to the Origin of Life: In the context of the origin of life, the first molecule is likely  RNA.  RNA's ability to store genetic information and catalyze its own replication (acting as both a genetic material and an enzyme) gives it a key role in early life. The  RNA World Hypothesis  suggests that RNA existed before amino acids or proteins, as it could facilitat...
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What is the difference between regulatory gene and structural gene?

Genes are basic units of heredity that carry instructions for the development and functioning of living organisms. Among various types of genes,  regulatory genes  and  structural genes  are essential for the proper functioning of cells, but their roles are quite different. Regulatory genes mainly control other genes, while structural genes directly code for proteins that form the body's structures or perform specific functions. To understand their differences clearly, we will compare them based on important criteria. 1. Based on Function The main function of  regulatory genes  is to control or regulate the expression of other genes. They produce regulatory proteins, such as repressors or activators, that influence whether structural genes are switched on or off. This control mechanism ensures that genes are expressed only when needed. In contrast,  structural genes  code directly for proteins or RNA molecules that are involved in building cellula...
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Subatomic Particles

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Atoms are the basic units of matter and are made up of smaller components called subatomic particles. There are many types of subatomic particles known to science, but in the context of basic atomic structure, only three are considered most important: electrons, protons and neutrons. These three particles differ in their location, charge and mass. Together, electrons, protons and neutrons form the complete structure of atoms. Their arrangement and interaction define the atom's properties, chemical behavior, and participation in physical and chemical processes. These subatomic particles laid the foundation of modern atomic theory and quantum chemistry. 1. Electron Electrons are negatively charged subatomic particles. They are extremely small in mass and are found outside the nucleus of the atom in specific regions called orbitals or shells. The charge of an electron is −1  and its mass is approximately 1/1836 of a proton or neutron, which is around 9.1 × 10⁻³¹ kg, meaning it is n...
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Differentiate between linked genes and unlinked genes?

Genes are specific sequences of DNA that code for proteins and determine traits in an organism. During the study of chromosomal theory of  inheritance, scientists found that not all genes behave the same way. Some genes tend to be inherited together while others assort independently. Based on this behavior, genes are divided into two types:  linked genes and unlinked genes.  This concept is very important in genetics because it helps in understanding how traits are passed on and how gene positions can be mapped on chromosomes. These differences are explained based on specific criteria: 1. Based on Chromosomal Location Linked genes  are located close to each other on the same chromosome. Because of their close physical proximity, they usually move together during meiosis and are inherited as a group. For example: In Drosophila melanogaster (fruit fly), the genes for eye color and wing shape are located close to each other on the X chromosome. Unlinked genes  are ...
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Can marriage between two albinos produce children with normal pigmentation?

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Albinism is a genetic condition where a person lacks melanin, the pigment responsible for the colour of skin, hair and eyes. It is usually inherited in an autosomal recessive manner. The most common forms of albinism, such as oculocutaneous albinism (OCA), are caused by mutations in genes like TYR, OCA2, TYRP1 etc. For a person to show albinism, they must inherit two copies of the defective allele, one from each parent. This means the genotype of an albino individual is generally homozygous recessive (aa). If both parents are albino due to mutations in the same gene, then their genotype would be aa, and the only gametes they can produce will carry the a allele. When we perform a cross: Parent 1: aa × Parent 2: aa Gametes: a a All children will also be aa, hence all children will be albino. Therefore, if both parents are albino due to the same gene, they cannot produce a normally pigmented child. However, in rare cases, albinism can result from mutations in different genes in e...
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Define and distinguish sex-linked, sex-limited and sex-influenced characters

In genetics, traits can be influenced or expressed differently depending on the sex of the individual. Some traits are linked to sex chromosomes, while others are affected by hormonal or physiological differences between males and females. To describe these traits more precisely, geneticists use three main terms:  sex-linked, sex-limited and sex-influenced traits.  Although these terms may sound similar, they refer to different types of genetic expression related to sex. Understanding the distinction among these three is important for grasping how certain traits are inherited and expressed differently in males and females. 1. Sex-linked characters: These are traits controlled by genes that are located on the  sex chromosomes,  usually on the X chromosome in humans. Because males have only one X chromosome (XY) and females have two (XX), the pattern of inheritance and expression is different in both sexes. Most sex-linked traits are X-linked, and very few are Y-linked...
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Give two examples of gene interaction resulting in the formation of structural proteins

Gene interaction refers to a situation where two or more genes influence the  same trait.  In the case of structural proteins, sometimes the final functional protein is not made from a single gene product but is the result of the combination of different polypeptides produced by different genes. Such interaction is especially important in the formation of complex structural proteins that require the association of multiple chains to become functional. Two good examples of this kind of gene interaction are seen in  haemoglobin and MHC (Major Histocompatibility Complex) molecules. 1. Haemoglobin (HbA) Haemoglobin is the oxygen-carrying protein found in red blood cells. The adult type of haemoglobin, called  HbA,  is a tetramer made up of two  alpha-globin chains and two beta-globin chains.  These chains are coded by different genes: The alpha-globin gene is located on  chromosome 16. The beta-globin gene is located on  chromosome 11. Both these...
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