Molecular Bases of Life

ERYTHROCYTES
COMPOSITION OF BLOOD. Need for anticoagulants; Erythrocytes and hematocrit; Serum and plasma; Erythropoiesis.
OXYGEN. Elements of physics.
MYOGLOBIN AND HEMOGLOBIN IN OXYGEN TRANSPORT. Structure and function of heme; Methemoglobin; Spectrophotometric differences between oxy- and deoxy-globins; Oxygen content.
STRUCTURE OF HEMOGLOBIN. Equilibrium curve for oxygen and P50; Allosterism; Molecular mechanisms during the deoxy-oxy hemoglobin transition; Allosteric effectors; Bohr effect; Carbon dioxide and 2,3-diphosphoglycerate; Monoxide and carbon dioxide; Forms in which CO2 occurs in the blood.
GENETICS OF HAEMOGLOBESNA. Variants; Natural selection and conservation; Molecular pathology of hemoglobin; Hemoglobin S and malaria resistance; Fetal hemoglobin and 2,3-DPG; Thalassemias.
CLINICAL ASPECTS. Primary and derived blood parameters; Glycated hemoglobin; Role of nitric oxide.
IRON METABOLISM. Iron absorption; Transferrin and Ferritin; Management of states of iron deficiency and overload.
HEME METABOLISM. Porphyries; 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; Transport proteins of metal ions; a1-antItrypsin; Haptoglobin and 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; Immunoglobulin structure and structure-function relationships; Classes of immunoglobulins; Generation of immunoglobulin diversity; Use of GI as diagnostic tools.
COAGULATION. Principles of hemostasis and Triad of Virchow; Platelets; Main features of intrinsic and extrinsic systems of factor X activation; Mechanisms of thrombin activation and role of vitamin K; Activation of fibrin; Control of coagulation and platelet aggregation; Hemophilia's.
GLYCOPROTEINS AND EXTRACELLULAR MATRIX
FUNCTIONS AND STRUCTURE. N- and O-glycoproteins; Sequon; Types of N-glycosylate glycoproteins; Biosynthesis of glycoproteins and secretory pathway; Polysaccharide biosynthesis; Processing and degradation of glycoproteins; Diseases and metabolic dysfunctions attributable to glycoproteins; ABO system.
PROTEOGLYCANS. Classes of glucosyl aminoglycans; Structure of proteoglycans; Main types of proteoglycans; Functions and pathophysiology of proteoglycans; Differences between glycoproteins and proteoglycans.
COLLAGEN. Ultrastructure of fibrils; Molecular structure of collagen types; Intra- and inter-molecular bonds; Composition in amino acids; Post-translational 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 beta adrenergic receptors; cAMP; Phosphatidyl inositol diphosphate; Phospholipase A2; Prostaglandins and leukotrienes; Signal transduction for steroid and thyroid hormones.
HORMONES. Functional classification of hormones; Hormone-receptor interactions; Agonists and antagonists; Hormonal cascades from neuro-sensory stigmas; Pituitary and hypothalamic hormones; Hypothalamic-pituitary-thyroid axis; Hypotalamus-pituitary-adrenal axis and hormones of the adrenal cortex; Glucocorticoids, mineralocorticoids and androgens; Biosynthesis and secretion of steroid hormones; Hypothalamic-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 the bones and teeth; Karyogenicity; Fluorine.
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; Strength of the buffer; The body's defenses against CO2 and H+; Blood buffer systems; CO2-bicarbonate system; CO2 hydration reaction; Henderson-Hasselbalch equation.
ACID-BASE COMPENSATION. pH-bicarbonate diagram; Measures that give information about the basic state in the fetus; Genesis of the main acid/base pathologies; Mechanisms of compensation of acid-base, renal and respiratory diseases; Renal control and H+ secretion; Swabs from the urine.
BIOCHEMISTRY OF THE KIDNEY. Main functions of the kidney; The nephron, functional unit of the kidney; Structure of the renal glomerulus; Mechanism of glomerular filtration; Composition and tone of glomerular filtrate; Diffusion of water, protein, glucose, creatinine, amino acids and other ions; Mechanism of resorption of Na and other components; Clearance measurement; Potassium; Aquaporins.
MUSCLE
STRUCTURE AND ULTRASTRUCTURE. Morphological differences between skeletal, cardiac and smooth muscles; Non-mechanical functions of muscle; Sliding filament model; Relationship between developed tension and cross-bridges; Thin and thick filament proteins; Myosin; Actin; Titin and nebulin; Dystrophin; Polymerization of actin and treadmilling; Tropomyosin and troponin; Actin-myosin interaction; Conformation of troponin.
Ca++ ROLE. Ca++ input mechanisms; Sarcoplasmic reticulum; Receptors sensitive to dihydropyridine and ryanodine; Ca-antagonists and blocking of the channels of the Na.
VARIOUS TYPES OF MUSCLE. Principles of bioenergetics, ATP and phosphocreatine; Red and white fibers; Metabolic responses to exercise and use of substrates; Skeletal and cardiac muscle; Role of phosphocreatine and adenylate kinase; Cardiac ischemia: Contraction of smooth muscle.
NON-MUSCULAR CONTRACTILE 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; C-centered free radicals; 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 pulmonary hypoxic vasoconstriction, Elastin, Basement membrane.
EPITHELIUM. Alveolar and surfactant cells, Mucus, Cystic Fibrosis and CFTR; Pulmonary edema and lung adjustments at high altitude. Defense against infections.
NERVOUS SYSTEM
NERVOUS TISSUE. Metabolic principles and morphology; Blood-brain barrier; Main features of neurons; Neuronal transport systems; Electrical and chemical synapses; Role of Na+/K+ ATPase; Ion channels, membrane depolarization and action potential
CHEMICAL SYNAPSES AND NEUROTRANSMIMETERS. Synaptic vesicles; Mode of neuronal transmission; Glutamate and GABA; Catecholamines, adrenaline and norepinephrine; Dopamine; Serotonin or hydroxltriptamine; Acetylcholine and notes on other neurotransmitters.
MECHANISM OF VISION. Morphology of retina and rods; Rhodopsin; Vitamin A or retinal; lsomerization of the retinal; Mechanisms of the effect on the entry of Na+ and hyperpolarization; Color vision and role of cones; Daltonism. Metabolism of the retina, glucose utilization; Crystalline and homeostasis of proteins; Senile and diabetic cataracts.
SENSES. Sensory transduction; Smell; Hearing; Taste.

The concept of "Precision Medicine" is introduced following the growing knowledge in genetics and molecular biology associated with the availability of clinical data that project new opportunities to personalize patient care and clinical management.
PRINCIPLES OF CELLULAR SIGNALING
The fundamental principles of "cell signaling" interactions mediated by G-protein coupled receptors and/or through coupled receptors with enzymatic activity are introduced. The mechanisms of modulation of signals through the role of 'scaffold' proteins are highlighted.
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 investigated.
GENE EXPRESSION CONTROL
The fundamental aspects related to the regulation of gene and genome expression are highlighted, with particular in-depth analysis of the role played by 'DNA-binding proteins' and transcription regulators.
The mechanisms of regulation of mRNA stability and the role of non-coding RNAs will also be considered.
GENOMIC INSTABILITY
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 "onco-suppressor" molecule par excellence, the related syndrome guides us in the dynamics of its mechanism of action.
· RecQ helicases: guardians of the genome
The RecQ helicases represent the guardians of the genome, a model of control of genomic stability, a syndromic paradigm the loss of 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 tumor by analyzing their role in normal cell function and homeostasis, as well as their oncogenic properties. We will also discuss how new technological approaches make it possible to discover molecular vulnerabilities that open up towards effective personalized medicine approaches.
MOLECULAR BASIS OF ONCO-HEMATOLOGICAL DISEASES
· The molecular 'landscapes' of Amyloid Acute Leukemia
Acute myeloid leukemias are neoplasms with low genetic instability, we will evaluate what emerges from the genomic and molecular profiles of the new generation· Leukemias 'Core Binding Factor'; a multi-step progression model that harmonizes genetics and epigenetics into a molecular continuum that can suggest new therapeutic approaches.· A->'Editing' RNAs: 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