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ENTRANCE TEST SYLLABUS FOR THE INSTITUTE OF NEUROSCIENCES KOLKATA (I-NK) PH D PROGRAM (2016-17) AFFILIATED UNDER THE UNIVERSITY OF CALCUTTA A. SYSTEM BIOLOGY a. Blood and Hemodynamics Hematopoiesis; Erythrocytes; Hemoglobin: Synthesis and functions Jaundice, Leukocytes Functions; Basic Mechanisms of Immunity, Leukemia, Eosinophilia, Hemostasis and Coagulation of blood, Anticoagulants, Blood groups, Rh- incompatibility, Blood transfusion, ESR, edema b. Cardiovascular Physiology Functional anatomy of heart, Principles and Significance of ECG, Cardiovascular reflexes; Neural and chemical regulation of blood pressure and cardiac cycle; Heart as a pump; Regional Circulations Normal values, Cardiac output: Measurement in Man, Physiological Variations; Changes in CVS during muscular exercise, Postural changes. Pathophysiology of Myocardial necrosis, Myocarditis, Cardiac Hypertrophy, Ischaemic Heart Disease and Heart failure. c. Respiratory Physiology Functional anatomy of Respiratory systems, Mechanics of Normal respiration, Principle of Lung function tests, Factors affecting respiratory resistance; Muscular control of airway diameter; Respiratory acidosis and alkalosis, Pulmonary blood flow, Hypoxia, Cyanosis, Asphyxia, Respiratory adjustments during muscle exercise, Hyperbaric conditions, Artificial Ventilation, Pulmonary edema and Dyspnoea, Respiratory system and immune function, Respiratory function during sleep. d. Neurophysiology Neurons, action potential, Synaptic transmission: chemical and electrical synapses, Peripheral nervous system, Functions of CSF, Blood Brain Barrier, Neuroglia and its function, Neuro & gliogenesis, neuronal migration, Myelination and dysmyelinating conditions. Synaptic plasticity, Importance of basal ganglia in the regulation of automatic movements; Vestibular apparatus and its functions, Physiology of cerebellum and Hypothalamus limbic system. Higher order functions of Pre frontal lobe and cerebral cortex. Neural control of Muscle tone and posture; Brain Waves, Sleep, wakefulness. e. Sensory physiology Sensation and perception, sensory receptors, coding of sensory modality, sensory circuits. Chemical senses: Taste system- Taste receptors, Taste bud, central taste pathways, abnormalities of taste. Olfactory system- Olfactory epithelium and receptors, Olfactory bulb, coding of olfactory information, anosmia and dysosmia. Visual Sense: Structure of photoreceptors, electrical activity of photoreceptors in light and dark phase, Role of visual cortex in perception, Acuity of vision, space perception and selective processes in perception. Auditory senses : Auditory receptors and pathway, Electrophysiology of cochlea, deafness and its causes. primary and secondary auditory cortical areas, auditory nerve potential, auditory fatigue, functions of Vestibular apparatus, Processing of speech; Perception of sounds in space. f. Gastrointestinal Physiology Neural control of digestive juice and bile secretion, cholesterol homeostasis, Functions of Gall Bladder and liver, GI hormones and Absorption of nutrients, Physiological basis of peptic ulcer, Diarrhoea and constipation, Starvation and Obesity. g. Renal Physiology Anatomy and histomorphology of kidney, renal blood flow, renal regulation of sodium-ion exchange, acidification of urine, diuresis, kidney function tests, Neural and endocrine control of renal functions; Renin-Angiotensin system, Micturition, Artificial kidney and Dialysis. h. Endocrinology and Reproductive Biology Endocrine glands, Hormones functions, Neuroendocrine regulation, Cytokines and growth factors, Disorders of endocrine functions: Hypothyroidism, Molecular Endocrinology: Mechanism of hormone actions: Membrane bound and intercellular receptors; steroid hormone-receptor interactions; membrane bound hormone-receptor interactions; second messenger in hormone action/signal transduction; recycling of receptors. Hormones in immune responses: Autoimmune endocrine disorders. Non-Conventional Endocrine Molecules in Health & Disease Reproductive organs and processes – gametogenesis, ovulation, neuroendocrine regulation. Fertilization, chemical, mechanical and immunological method of controlling fertility, in vitro fertilization. B. CELLULAR & MOLECULAR BIOLOGY a. Cellular organization, cell division, cell to cell communication and signalling Cell structure and function; Structural organization and function of intracellular organelles; Membrane structure and function; Cell cycle & control of cell of division; Cell signalling; Cellular communication; Cancer & Control of gene expression at transcription and translation level. b. Biomolecules and their principles of interactions Bronsted-Lowry Concept of Acids and Bases, Buffers: Henderson-Hasselbalch equation, Biological buffer systems, pH of body fluids. Bonds in Biological macromolecules and building blocks. Molecular thermodynamics. Protein - Conformation of proteins and polypeptides – Amino acid sequences. Primary, secondary, tertiary, quarternary and domain structure of proteins. Proteins as informational macromolecules; chemistry of amino acids; peptide subunits, α-helix, β-sheet and collagen structure, Helix-coil transition; Protein folding and its problems: Role of chaperons. Physical Properties of Proteins: Shape and Size, Molecular weight, Colloidal nature, Denaturation, Amphoteric nature, Solubility, Optical Activity, Chemical Properties of Protein: Hydrolysis, Reaction involving COOH group, NH2 group, R group, SH group. Carbohydrates - Importance, Nomenclature, Classification, Asymmetry, Optical Isomerism.General structure of monosaccharide, disaccharide, oligosaccharides, polysaccharides (Lactose, Maltose, Cellobiose, Isomaltose, Trehalose, Starch, Glycogen, Cellulose, Pectin, Chitin, Heparin). Structural characteristics of polysaccharides, glycolipids, glycoproteins and peptidoglycans. Nucleic Acids: Molecular structure of DNA (Nucleosides, Nucleotides), Internucleotide linkages, Base composition, Evolution of Watson-Crick model, Double helical structure, Denaturation and renaturation, Molecular weight, Length, Shape and Size, Variants of Double helical DNA, DNAs with unusual structures, Single stranded DNA, RNA. Differences with DNA, rRNA, tRNA, mRNA, hnRNA; Structure and stability, Characteristics of viral, prokaryotic and eukaryotic DNA. Lipids: Importance, Definition, Alcohols and Fatty Acids, Biological roles of lipids, Classification: Simple Lipids and Compound Lipids, Chemical Properties - Properties of Fats and oils: Solubility, Melting Point, Insulation, Emulsification, Surface Tension, etc. c. Enzymes and Reaction Kinetics Enzyme definition, Biological roles, Chemical nature and Characteristics of enzymes, Specificity of enzyme action, Thermostability Structural basis of enzyme function: Coenzymes, Activators, Inhibitors (Competitive, Noncompetitive, Uncompetitive), Isoenzymes, Kinetics of enzyme action; Michaelis Menten equation, Lineweaver-Burk equation, Significance of Km and Vmax values, Active site, Regulation of enzymatic activity; Allosteric enzymes and their modulators. Technical approach to the study of enzyme activities; Purification and characterization of enzymes; Clinical enzymology. Diagnostic and therapeutic uses of enzymes. d. Bioenergetics and Metabolism Concepts of free energy and strategies of energy metabolism; High energy biomolecules and coupling phenomenon, energy rich bonds, weak interactions, group transfer, Biological energy transducers and bioenergetics; high-energy biomolecules; Oxidative phosphoryltion and mitochondrial function; Uncouplers and inhibitors of oxidative phosphorylation; Extramitochondrial electron transport chains; Oxygen toxicity and superoxide dismutase. Application of thermodynamics in biological systems. Biophysical Methods: Basic principles and applications. Molecular Biophysics Forces involved in biomolecular interactions, Ramachandran plot, dihedral / torsional angles, supercoiling of DNA (linking, twisting, and writhing- brief ideas), Interaction of ligands with biomolecules. Protein folding (Myoglobin, ribosome), use of various techniques to determine the native state of protein (UV, Florescence). Metabolism : Definition of metabolism, Catabolic pathways, Anabolic pathways, Metabolism of carbohydrate, Amino acid, Lipid and Nucleic acid. Regulation of metabolic pathways, Metabolism in the brain and effect of malnutrition, Neuropeptides: Dopamine, serotonin, acetylcholine, noradrenaline pathways. Metabolic diseases involving Carbohydrate, Lipid; Amino Acid, and Nucleic acid Metabolism. e. Molecular biology Molecular Organisation of eukaryotic genome: Packaging of eukaryotic DNA into chromosomes, nucleosomes, Chromosomal aberration. DNA as the molecule of information: Gene and its organisation (exons, introns), regulatory DNA sequences (cis-acting and trans-acting regulatory elements). DNA replication and its regulation; DNA damage and repair, Recombination; Transcription, RNA synthesis (mRNA, tRNA, rRNA), RNA processing in eukaryotes; RNA polymerases, Operon, Genetic-code, Translation, Protein biosynthesis & regulatory factors, Mechanism of action of inhibitors, Translation. Regulation of gene expression, both prokaryotic and eukaryotic: Regulation of transcription, transcription factors, motifs, RNA splicing and post-transcriptional modification, catalytic RNA, Rearrangement of DNA, Antisense RNA, exon shuffling, RNA editing, and mRNA transport, Regulatory RNAs. f. Human genetics and Molecular diagnostics Organisation of human chromosomes; Structural alteration of Chromosome (Deletion, duplication, inversion, translocation, ploidy); Inheritance: Concept in Mendelian Inheritance – dominance, segregation, independent assortment; Pedigree analysis. Concept of gene - locus, allele; Extensions of Mendelian principles: Codominance, incomplete dominance, gene interactions, pleiotropy, genomic imprinting, penetrance and expressivity, phenocopy, linkage and crossing over, sex linkage, sex limited and sex influenced characters. Gene mapping : Linkage maps (lod score analysis), mapping by using somatic cell hybrids (karyotyping), mapping with molecular markers (association study), development of mapping population in plants. Extra chromosomal inheritance: Inheritance of Mitochondrial and chloroplast genes, maternal inheritance. Population Genetics (Hardy-Weinberg equilibrium, selection, genetic drift, gene flow, inbreeding, genetic diversity, races) Genetic variations (Mutation, polymorphism, etc); Mutation: Types, causes and detection, mutant types – lethal, conditional, biochemical, loss of function, gain of function, germline vs somatic mutants, insertional mutagenesis. The Human genome project (HGP): Implications and future prospects. A brief overview on chromosomal abnormalities Genetic disorders, single gene disorder, multifactorial diseases, Molecular approaches to characterize genetic diseases - Genome mapping. Immunogenetics; Genes in Development and Differentiation; Cancer Genetics; Molecular diagnosis of genetic disorders: Molecular diagnostics - Gene function evaluation and mutation detections using techniques, such as, PCR, RT-PCR, RFLP, Oligonucleotide probes, DNA-probes, DNA blotting, DNA fingerprinting and SNP analysis, Genetic screening and genetic counselling; DNA microarray, knock out in mice, transgenic mice, Southern blot, northern blots, DNA sequencing, single nucleotide polymorphisms, methods for identification of mutations, molecular markers linked to disease resistant genes. PCR based diagnostics, DNA fingerprinting, DNA chip. Neurogenetic diseases – Molecular basis of genetic diseases; Autosomal (recessive and dominant) and X-linked neurological diseases – Neurodegenerative diseases, unstable mutation (repeat expansion) causing spinocerebellar ataxias, Huntington’s disease, Myotonic dystrophy, Friedreich’s ataxia, Fragile-X syndrome, etc., and molecular pathology. Metabolic defects causing neurological diseases (Tay-Sach’s, Gaucher’s diseases, etc). Genetics of Migraine, Epilepsy and other neurological diseases of complex inheritance - Complex genetic diseases, gene environment interactions, various loci identified, approach to identify the genetic contributors. g. Physiology of excitable cells Nerve: Axoplasmic flow and transport mechanism in the axons; Problem of nerve conduction with reference to single nerve fibre study; Nature of nerve fibre excitation and interpretation of action potential; voltage gated channels and gating currents. Voltage clamp of nerve fibre membrane and membrane currents. Patch clamp and unitary activity of membrane channels. Neuro-Muscular Junction (NMJ): Neuro-muscular transmission – Electrical and Biochemical events; Acetylcholine receptor – Protein and antigenic structure and its relevance to myasthenia gravis, structure function relationship; Acetylcholine – Structure-function relationship, Metabolism and Regulation; Drugs acting at NMJ; Motor unit, MUAP, motor unit recruitment patterns. Muscle: Protein components and contraction mechanism in different types of muscles. Excitation – contraction coupling, Role of fast and slow channels, Ca2+ - binding protein including calmodulin, Muscle fibre types. h. Basic Immunology – Immunoglobins, organization and expressions of Ig genes; B cell maturation, activation and differentiation; MHC/ HLA; antigen processing and presentation; T-cells, T-cell receptors, T-cell maturation, activation and differentiation; cytokines; cell mediated and humoral effector responses, auto immunity, immunodeficiency diseases, transplantation immunology, cancer and immune system. Monoclonal and polyclonal antibodies, monoclonal antibody technique. Cellular immunology, Neural cell immunology, Microglia (antigen presentation), Neuro-immunomodulation — Neuro-immunology, Neurodiversity. Immune Diversity: Lymphocytes that respond to individual antigens, immunoglobulin genes, diversity of germline information, T-cell receptors, somatic mutations and diversity, immunogenetics. Relation between neuroendocrine system and immune system, feed back regulation of neuroendocrine – immune network. Stem cell differentiation – embryonic/fetal/adult cell transplantation i. Biotechnology Concepts of Biotechnology: General & historical, aims, achievements and prospects. Microbial technology : Fermentation technology, production of ethanol, penicillin and other antibiotics, microbial-insecticides, enzymes, amino acids etc. and application in industry. Use of microorganisms in pollution control. Enzyme biotechnology: Immobilized enzymes and its application in industry. Principles of protein engineering. Biotechnology as applied to Immunology. j. Environmental science Biochemical basis of environmental health and environmental toxicology, Biotransformation of xenobiotics in general and absorption, transport, effects and biotransformation C. NEUROBIOLOGY a. Gait Analysis: Fundamentals of Gait Analysis, Biomechanics of human locomotion - basic parameters of human gait (temporal – spatial gait parameters, kinematic parameters, kinetic parameters and muscles activity – EMG ), Normal and pathological gait, Methods of gait analysis in clinical practice, Biomechanics of human posture – stability and postural control, Ground Reaction Forces. b. Stress Physiology . Oxidants, oxidative stress, oxidative damage, antioxidants. Enzymatic and non-enzymatic antioxidants. Mechanisms of actions. Fenton-reaction, Haber-Weiss reaction. Stress-induced disorders and role of antioxidants in ameliorating these disease situations. c. Cognitive Function Mechanism in Learning & Memory; limbic system - the centre of emotion. Function of the Brain in Communication – Language input and output, function of the corpus callosum and anterior commissure to transfer thoughts, memories, training and others. Thoughts, consciousness and memory (short and long term). Basal ganglia and cognitive function. Biology and biochemistry of depression. d. Introductory Psychology Definition of Psychology, application of Psychology, methods in Psychology, Principles of Learning, Behaviour, thinking and language, emotion and stress, social perceptions, influences and relationships, attitudes, Psychological assessment and testing, Abnormal Psychology, Therapy for Psychological distress. e. Neuropathology and Clinical Neurology Epilepsies and Convulsive diseases, Cerebrovascular diseases, Dementia, Parkinson's Disease, Spinocerebellar ataxia Torsion dystonia, Progressive Supranuclear Palsy (PSP), Motor neuron Diseases [Amyotropic Lateral Sclerosis (ALS)], Lower Motor Neuron Disorder - Kennedy's Disease, others; Upper Motor Neuron Disorder - Primary Lateral Sclerosis, Familial Spastic Paraplegia; Ataxia: (Frederich's Ataxia, others); Demyelinating Diseases: (Multiple Sclerosis, Other Demyelinating Diseases, Encephalomyelities); Viral diseases - Encephalitis etc., Prions (Proteinaceous infectious particles) – Transmissible Neurodegenerative diseases; Nutritional and Metabolic Diseases, Neurocutaneous Syndromes, Developmental Disorders. Mechanism of development of degenerative diseases: Clinical Neurology – Epidemiology, Anatomical Diagnosis, Pathological diagnosis, Symptoms of neurological diseases, examination of Nervous system, Neuroimaging, Neuroradiology: CT, MRI, Mylography; Interventional Radiology - PET (Positron Emission Tomography) – CVA, Epilepsy etc., Single - Photon Emission Computed Tomography, MR Spectroscopy, Magnetic Source imaging. f. Neurochemical basis of Neuropathology Research in neuropathology/neurological disorders involves specific neurochemical changes. neurochemical basis of brain disorders and principles and applications of important diagnostic tools. Neurochemical and molecular mechanisms of peripheral Neuropathy; Diseases involving myelin; Multiple sclerosis and other demyelinated disorders; Genetic disorders of Lipid, glycoprotein, and Mucopolysaccharide metabolism; Duchenne Muscular dystrophy: Molecular, genetic aspects and diagnostic characteristics; Nutritional and metabolic Diseases: Disorders of amino acid metabolism, Wernicke-Korsakoft syndrome; Pellagra; Alcoholic Cerebellar Degeneration; Metabolic Encephalopathies and Coma Neurotransmitters and disorders of basal ganglia; Molecular targets of abused drugs; Ischemia and hypoxia; Epileptic seizures; Genetics and diagnosis of Huntington disease and other triplet repeat disorders; Alzheimer’s disease: Molecular, genetic, immunological aspects and diagnostics Theories of aging; Neurobiology of aging: cellular and molecular aspects of neuronal aging; Aging and neurodegeneration; Parkinson’s disease Motor Neuron Diseases; Prion’s Disease; Biochemical aspects of the psychotic disorders; Biochemical basis of mental illness: Anxiety disorders; Mood disorders; Attention disorders; Schizophrenia g. Bioinformatics for Neuroscience Bioinformatics: History, scope and importance; Computers, internet, www, and NCBI; Neuroinformatics: Concept and applications; DNA sequencing and analysis; Protein sequencing and analysis Databases, tools and their uses; Sequence alignment; Predictive methods using DNA sequences; Predictive methods using protein sequences; Pharmainformatics and drug discovery h. Neurophysiological Instrumentation: Acquisition of data for various physiological parameters using Biopac Electrophysiological recording setup: a) EEG ; b) ECG ; c) EMG, EOG d) Heart rate, respiration, pulse rate, heart sound, etc. Bio-Medical Instrumentation: CT scan, ultrasonography, MRI, pulmonary function analyzer, biomedical telemetry D. METHODS APPLICABLE IN BIOLOGY a. Biophysical and Biochemical Methods pH meter use, buffer preparation, Basic principles of Spectrophotometer, absorption spectroscopy (UV-Visible); Protein, DNA measurement. Optical Microscopy, phase contrast microscopy and their application in cell biology. Flow cytometry and confocal microscopy. Cell fractionation: Homogenization and ultrasonication, Ultracentrifugation, Differential and density gradient centrifugation for separation of cell fractions; Principle of chromatography and protein purification, ion exchange, gel filtration chromatography, SDS-PAGE, AGE. Enzyme kinetics – Enzyme assays, determination of effect of pH, temperature on enzyme activity, Michaelis-Menten equation, Km, Vmax determination. Experimental design and data analysis Principle of experimental design; Collection of data, sampling and presentation of data: Statistical tables, charts and graphs; Centering constants and their measurements: Mean, median and mode; Measurement of variabilities like deviation, standard deviation, standard error, etc.; Tests of significance: Student t-test and Chi-square test; ANOVA- one way and two-way; Coefficient of correlation and regression