Molecular Bases of Life

Erythrocytes
COMPOSITION OF BLOOD. Need for anticoagulants; Erythrocytes and hematocrit; Serum and plasma; erythropoiesis.
OXYGEN. Notes of physics.
MYOGLOBIN AND HEMOGLOBIN IN OXYGEN TRANSPORT. Structure and function of the heme; Metaemoglobin; Spectrophotometric differences between oxy- and deoxy-globins; Oxygen content.
STRUCTURE OF HEMOGLOBIN. Equilibrium curve for oxygen and P50; Allosterism; Molecular mechanisms during the transition deoxy-hemoglobin bones; Allosteric effectors; Bohr effect; Carbon dioxide and 2,3-diphospholerate; Monoxide and carbon dioxide; Forms in which CO2 occurs in the blood.
GENETICS OF HEMOGLOB! Na. Variants; Natural selection and conservation; Molecular pathology of hemoglobin; Hemoglobin S and malaria resistance; Fetal hemoglobin and 2,3-DPG; Thalassaemia.
CLINICAL ASPECTS. Primary blood parameters and derivatives; Hemoglobin; Role of nitric oxide.
IRON METABOLISM. Iron absorption; Transferrin and Ferritin; Management of iron deficiency and overload states.
METABOLISM OF THE EME. Mr Porfirie; Destinies of bilirubin and jaundice.
Plasma
PLASMA PROTEINS. Generality.
ONCOTIC PRESSURE. Osmotic and oncotic or colloidal pressure; Regulation of fluid distribution and genesis of tissue edema.
CLINICAL SIGNIFICANCE OF PLASMA PROTEINS. Albumin; Albumin/globulin ratio; Metal ion transport proteins; a1-antItrypsin; Aptoglobin and the fate of erythrocytes; Acute phase proteins; Protein electrophoresis; Isoenzymes; Meaning of their alterations.
IMMUNE SYSTEM. Molecular and cellular components of the immune system and mechanisms of immune responses; Theory of clonal selection, versatility, specificity and memory of immune responses; Structure of immunoglobulins and structure-function relationships; Classes of immunoglobulins; Generation of immunoglobulin diversity; Use of GIs as diagnostic tools.
COAGULATION. Princes of Hemostasis and Virchow Triad; Platelets; Main characteristics of intrinsic and extrinsic X-factor activation systems; Mechanisms of activation of thrombin and role of vitamin K; Activation of fibrin; Control of clotting and platelet aggregation; Hemophilia.
GLICOPROTEINS AND EXTRACELLULAR MATRIX
FUNCTIONS AND STRUCTURE. N- and O-glicoproteins; Mr Sequon; Types of N-lysosylated lycoproteins; Biosynthesis of lycoprotelnes and secretory; Polysaccharide biosynthesis; Processing and degradation of lycoproteins; Metabolic diseases and dysfunctions attributable to lycoproteins; ABO system.
PROTEOGLICANS. Classes of glucoseminoglycans; Structure of proteoglycans; Main types of proteoglycans; Functions and physiopathology of proteoglycans; Differences between glycoproteins and proteoglycans.
COLLAGEN. Ultrastructure of fibrille; Molecular structure of collagen types; Intra- and inter-molecular bonds; Composition in amino acids; Post-transactional modifications of some amino acids; Carbohydrates; Collagen biosynthesis; Main pathologies of collagen.
NON-COLLAGEN PROTEINS OF THE EXTRACELLULAR MATRIX. Elastin and main pathologies; Fibronectin, role of isoforms; Laminin.
HORMONES AND INTRACELLULAR COMMUNICATION
SIGNAL TRANSDUCTION. General mechanisms and interaction with receptors; G protein and adrenergic beta receptors; cAMP; Phosphatidyl inositol diphosphate; Phospholipase A2; Prostaglandins and leukotrienes; Signal transduction for steroid hormones and thyroids.
HORMONES. Functional classification of hormones; Hormone-receptor interactions; Agonists and antagonists; Hormonal cascades from neuro-sensory constipation; Pituitary and hypothalamic hormones; Hypothalamus-pituitary-thyroid axis; Hypotaxic-pituitary-adrenal axis and adrenal cortex hormones; Glucocorticoids, mineracocorticoids and androgens; Biosynthesis and secretion of steroid hormones; Hypothalamus-pituitary-gonad axis; Growth hormone axis; Prolactin axis; Catecholamines; Pancreatic hormones.
CALCIUM AND PHOSPHATE METABOLISM
CALCIUM. Distribution in the body, needs and flows of calcium and phosphate; Parathyroid hormone, calcitonin and vitamin D; Osteoporosis, osteomalacia and rickets; Bone remodeling; Osteoblasts and bone growth; Osteoclasts and demineralization; Calcium in bones and teeth; Karyogenicity; Fluoride.
WATER AND ELECTROLYTES
DISTRIBUTION OF WATER, CATIONS AND ANIONS. Distribution of water in the body; Anion Gap; Cations and anions; Water balance.
ACID-BASE SYSTEMS AND THEIR REGULATION. Recalls, buffer systems; Buffer strength; Body defenses against CO2 and H+; Blood buffer systems; CO2-bicarbonate system; CO2 hydration reaction; Henderson-Hasselbalch equation.
ACID-BASE COMPENSATION. Diagram pH-bicarbonates; Measures that give information about the base state in the fetus; Genesis of the main acid/base diseases; Mechanisms for compensating for acid-base, kidney and respiratory diseases; Renal control and secretion of H+; Swabs from the urine.
KIDNEY BIOCHEMISTRY. Main functions of the kidney; The nephron, functional unit of the kidney; Structure of the renal glomerule; Mechanism of glomerular filtration; Composition and tone of glomerular filtrate; Diffusion of water, proteins, glucose, creatinine, amino acids and other ions; Mechanism of resorption of Na and other components; Clearance measure; Potassium; Aquaporine.
Muscle
STRUCTURE AND ULTRASTRUCTURE. Morphological differences between skeletal, cardiac and smooth muscles; Non-mechanical functions of the muscle; Sliding filament model; Relationship between developed voltage and cross-bridges; Thin and thick filament proteins; Myosin; Actina; Titin and nebulin; Dystrophine; Polymerization of actin and treadmilling; Tropomyosin and troponin; Actin-myosin interaction; Conformation of troponin.
CA++ ROLE Ca++ input mechanisms; Sarcoplasmic reticulum; Receptors sensitive to dihydropiridine and rianodine; Ca-antagonists and blockage of the Na channels.
VARIOUS TYPES OF MUSCLE. Principles of bioenergetics, ATP and phosphocreatin; Red and white fibres; Metabolic responses to the exercise and use of substrates; Skeletal and cardiac muscle; Role of phosphocreatine and adenylate kinase; Cardiac Ischemia: Contraction of the smooth muscle.
NON-MUSCULAR CONTRACTAL UNITS. Other roles of actin; Alpha-actinin.
FREE RADICALS AND OXIDATIVE STRESS
CHEMISTRY AND PROPAGATION MECHANISM. Oxygen and Reactive Oxygen Species; Role of mitochondria and peroxisomes; Other biological reactions that generate free radicals; Free radicals centered on C; Markers of free radical damage; Central free radicals on metals; Nitric oxide.
SCAVENGERS. Scavenging systems; Antioxidants and oxidative stress control systems.
AGING. Age-related fragility; the Hayflick limit; Telomeres and telomerases; Theories of aging.
BIOCHEMISTRY OF RESPIRATION
RESPIRATORY FUNCTION. Alveolus, Gas Exchange and Transport of O2 and CO2, Oxygen sensing; Nitric oxide, carbon monoxide.
ENDOTHELIUM. Role of NO and vasoconstriction hypoxic pulmonary, Elastin, Basal membrane.
EPITHELIUM. Alveolar and surfactant cells, Mucus, Cystic Fibrosis and CFTR; Pulmonary edema and pulmonary adjustments at high altitude. Defense against infections.
Nervous system
NERVOUS TISSUE. Metabolic principles and morphology; Blood and blood barrier; Main characteristics of neurons; Neuronal transport systems; Electrical and chemical synapses; Role of Na+/K+ ATPasi; Ion channels, membrane depolarization and action potential
CHEMICAL SYNAPSES AND NEUROTRANSMETORS. Synaptic vesicles; Mode of neuronal transmission; Glutamate and GABA; Catecholamines, adrenaline and norepinepinethine; Dopamine; Serotonin or hydroxyltryptamine; Acetylcholine and notes on other neurotransmitters.
MECHANISM OF VISION. Morphology of retina and rods; Mr Rodopsin; Vitamin A or retinal; lsomerization of the retinal; Mechanisms of the effect on the input of Na+ and hyperpolarization; Color vision and role of cones; daltonism. Metabolism of the retina, use of glucose; Crystalline and protein homeostasis; Senile and diabetic cataracts.
SENSES. Sensory transduction; Smell; Hearing; taste.

PRINCIPLES OF CELLULAR SIGNALING
The fundamental principles of cell signaling interactions mediated by G-protein-coupled receptors and/or through receptors coupled with enzymatic activity are introduced. Signal modulation mechanisms are highlighted through the role of 'scaffold' proteins.
The role of cellular signaling is developed through the treatment of the molecular mechanisms underlying MEN2 syndromes, they are discussed as a molecular model of alteration of tyrosine-kinase receptors; an example of clinical/molecular management in endocrinology.
In addition, as an example of somatic alterations, the role of tyrosine-kinase receptors in the onset of acute leukemias is deepened.
CONTROL OF GENE EXPRESSION
The fundamental aspects related to the regulation of gene and genome expression are highlighted, with particular in-depth study of the role played by DNA-binding proteins and transcription regulators.
Mechanisms for regulating the stability of mRNAs and the role of non-coding RNAs will also be taken into account.
GENOMIC INSESTABILIA
The concepts of genetic/chromosomal instability are discussed with an overview of some models proposed for the understanding of the phenomenon that acts as a motor in neoplastic transformation.
· Li Fraumeni syndrome
Paradigm of the mechanisms by which neoplastic progression acquires functions. p53 is the main "onco-suppressor" molecule, the related syndrome guides us in the dynamics of its mechanism of action.
· RecQ helix: genome guardians
RecQ helicases represent the guardians of the genome, a model of control of genomic stability, a paradigm that sindromically loses their function.
MOLECULAR BASIS OF AGING AND RELATED DISEASES
We will explore the biological causes of aging by analyzing in detail the molecular mechanisms involved, discussing the implications of aging in the development of diseases
ENVIRONMENT AND EPIGENETICS IN THE DEVELOPMENT OF DISEASES
We will analyze the role of epigenetic mechanisms and their contribution to the development of diseases. We will further deepen the concept of epigenetics closely linked to the role that the environment plays in the development of diseases by discussing its molecular implications.
MOLECULAR MECHANISMS INVOLVED IN TUMOR DEVELOPMENT
We will explore the main molecular pathways involved in the development of different types of human cancer by analyzing their role in normal cellular function and homeostasis, as well as their oncogenic properties. We will also discuss how new technological approaches allow us to discover molecular vulnerabilities that open up to effective approaches to personalized medicine.
MOLECULAR BASIS OF ONCO-HEMATOLOGICAL DISEASES
· The molecular landscapes of Acute Myeloid Leukemia
Acute myeloid leukemias are neoplasms with low genetic instability, we will evaluate what emerges from the next generation genomic and molecular profiles
· Leukemias 'Core Binding Factor'; a multi-step progression model that harmonizes genetics and epigenetics in a molecular continuum that can suggest new therapeutic approaches.
· A->THE RNA 'Editing': the "ADAR" side of leukemias.

One of the most relevant post-transcriptional changes between the plasticity functions of the genome and its bivalent role in neoplastic transformation is discussed.
GENETIC AND CELLULAR ENGINEERING
We will analyze the molecular bases that allow to manipulate the identity of cells and their genetic content by discussing technological strategies and potential therapeutic approaches.