Micronutrients, vitamins and coenzymes. Minerals. Structure and function correlations. Visualization of molecular structures with rasmol and pymol software. Laboratory activities on protein science applied to nutritional biochemistry. Macronutrients, pathways of assimilation and biosynthesis. Biosynthesis of amino acids. Biosynthesis of lipids (cholesterol, fatty acids). Fiber metabolism, fructose metabolism. Functions of the intestinal microbiota. Breastfeeding, allergies to milk proteins. Nutraceuticals. Biochemical-molecular bases of the main pathological conditions related to human nutrition (hypercholesterolemia, diabetes, celiac disease, ethanol toxicity). Insight into gender equality, particularly as it relates to eating disorders.

History of plants in human nutrition, domestication, hybridization, and selection. Edible parts of plants. The main angiosperm families. Nutritional principles, antinutritional factors, secondary metabolites, and product categories. Poisonous plants. Edible algae. Phytoalimurgy. Plants for animal nutrition. Food preservation and shelf life. Practical laboratory activities on food adulteration.

Nutrients in food: proteins, carbohydrates and lipids. Amino acids: chemical properties involved in food technology. Essential and limiting amino acids, complementarity and contemporaneity, integration and fortification. Carbohydrates. Chemical reactivity in food. Maillard reactions. Lipids: composition and classification. Essential fatty acids. Unsaponifiable fraction. Fat-soluble and water-soluble vitamins. Mineral salts, organic acids, polyphenols. Food additives, toxicity evaluation, acceptable daily intake, technology e fields of applications. Principal additives: colours, sweeteners, preservatives, antimicrobials, antioxidants, stabilizers, thickeners, gelling agents, emulsifiers, flavor enhances, and other additives. Technological adjuvants and extraction solvents. Flavors. Cereals and derived products. Production of flour, bread and pasta. Fats: production, rectification, hydrogenation and transesterification. Lipid oxidation. Animal fats, olive oil, seed oils, margarine. Vegetables: fresh products and canned vegetables. Dairy products (milk, yoghurt, cheese and butter): technology and characteristics. Meat: composition and cured products. Fishes and canned products. Eggs and derived products. Alcoholic beverages. Wine: wine-making, composition, regulation of Origin Appellations. Special wines. Spirits and liqueurs. Beer: composition and brewing technology. Food toxicology and undesirable compounds in food: antinutrients and natural toxics, food allergens, biogenic amines, mycotoxins, toxic compounds related to technological processes, heavy metals, pesticides residues, residues related to zootechnic practices and veterinary drugs, contaminants from packaging and environment.

Difference between food and nutrition and between food and nutrient Classes of food and their nutrients Physiological functions of nutrients Energy balance of the body Composition of the human body and methods of evaluation Fat mass and lean mass Adipose organ. differences and functions of white and brown adipose tissue. Endocrine alterations due to excess adipose Hints of metabolism. Items that contribute to daily energy expenditure. Methods of assessing basal metabolism Hints of thermodynamics of open systems Chemical senses and their role in nutrition. sensory function, afferents to different parts of the nervous system Central and peripheral control of hunger and satiety: hippocampus, hunger hormones and satiety factors. Central orexigenic and anorexigenic circuits. Physiological and behavioral effects of circuits Macronutrients: definition Carbohydrates: structural characteristics, functions in the body, classification, starch and glycogen. Blood glucose control Lipids: structural features and functions in the body. Saturated, unsaturated, polyunsaturated fatty acids. Essential fatty acids and role in the eicosanoid pathway Proteins: structural features and functions in the body. Essential aminoacids. Methionine-homocysteine cycle. Deamination and transamination Micronutrients: definition Vitamins: water-soluble and water-insoluble vitamins. Characteristics of each vitamin, food sources and physiological role Mineral salts: macroelements, trace elements, and trace elements. Physiological function of sodium, potassium, chlorine, calcium, phosphorus, magnesium, sulfur, iron, iodine, zinc, cobalt, copper, fluorine, and selenium Nutraceuticals: what they are0o and where they are found. Prebiotics and probiotics. Antioxidants and nutraceuticals that contribute to the physiological/metabolic functions of the organism Digestive system: general characters of functional anatomy. Motor activiity of the intestinal smooth muscle and cells of Cajal. Nervous control of the digestive tract: enteric nervous system and the role of the autonomic system Hormonal control of the digestive tract: tipic hormones of digestive function and feeding control Characteristic motor patterns: peristalsis, segmentation, haustration, CMM, receptive relaxation, sphincter control Chewing and swallowing. Initial digestion. Salivary glands . control and secretion. Unconditioned and conditioned reflex (Pavlov's dog) Esophagus: concept of secondary vago-vagal peristalsis Stomach: motor activity of the stomach from the fundus to the antrum. Pyloric sphincter control and gastric emptying. Gastric glands and secretion production. Morpho-functional transition of ossicular glandular cells Small intestine: motor activity and digestion and absorption in duodenum, jejunum and ileum. Control of the sphincter of Oddi macroelements, trace elements, and trace elements. Physiological function of sodium, potassium, chlorine, calcium, phosphorus, magnesium, sulfur, iron, iodine, zinc, cobalt, copper, fluorine, and selenium Nutraceuticals: what they are0o and where they are found. Prebiotics and probiotics. Antioxidants and nutraceuticals that contribute to the physiological/metabolic functions of the organism Digestive system: general characters of functional anatomy. motor activity of the intestinal smooth muscle and cells of Cajal. Nervous control of the digestive tract: enteric nervous system and the role of the autonomic system Hormonal control of the digestive tract: tipic hormones of digestive function and feeding control Characteristic motor patterns: peristalsis, segmentation, haustration, CMM, receptive relaxation, sphincter control Chewing and swallowing. Initial digestion. Salivary glands . control and secretion. Unconditioned and conditioned reflex (Pavlov's dog) Esophagus: concept of secondary vago-vagal peristalsis Stomach: motor activity of the stomach from the fundus to the antrum. Pyloric sphincter control and gastric emptying. Gastric glands and secretion production. Morpho-functional transition of ossicular glandular cells Small intestine: motor activity and digestion and absorption in duodenum, jejunum and ileum. Control of the sphincter of Oddi Pancreas: structure of the gland. Acinar and ductal component. Nervous and hormonal control of pancreatic secretion. Enzymatic component and enzymes. Aqueous bicarbonate component Liver: structure of the hepatic lobule and portal triad. Bile production. Liver functions in metabolism, storage, detoxification, transamination Large intestine: haustrations and formation of fecal mass. Water and salt reabsorption Defecation: control of the external and internal anal sphincter. Hints on the intestinal microbiota The immune system of the intestine: the wall immune structures and morpho-functional organization. Role of the microbiota

An overview of systematics, biology and ecology of fungi. The fungi and food. Preparation of microscopic slides obtained from fungal culture. Use of analytical keys to identify the main fungal taxa.

Introduction to food microbiology and biotechnologies. Lactic, acetic, and propionic bacteria: general characteristics, taxonomy, metabolism. Fermentations. Yeasts. Other microorganisms involved in food production. Starters. Fermentation equipment. Bioreactors and how they work. Continuous and batch fermentations. Upstream and downstream operations. Amino acid production: glutamate, aspartate, lysine, and proline. Polysaccharide production: xanthan, gellan gum, curdlan. Citric acid production. Single Cell Proteins (SCP): definition, advantages and disadvantages. Microorganisms as SCP. Examples of SCP. Bread and baked products: classification, raw materials. Gluten: formation and role in doughs. Chemical and biological leavening. Everyday bread (alcoholic fermentation) and sourdough bread (alcoholic and lactic fermentation). Interaction between yeasts and lactobacilli in sourdough bread production. Vinegar: legislation, raw materials. Acetic acid bacteria and acetification. Vinegar spoilage. Balsamic vinegar and other types. Cured meats: classification, definition, and processing. Microflora involved in transformation: role of microorganisms. Salami fermentation. Cheese: definition and types. Raw material: milk and its properties. Production scheme of raw, semi-cooked, and cooked cheese. Selection and use of starters for cheese production. Wine: legislation, history, and definition. Natural fermentation and fermentation guided by starters. Sparkling wine production using different methods. Cocoa, coffee, tea: history and definition, biotechnological processes. Fermented foods. Beer: history, raw materials, and processing steps. Spontaneous fermentation.

• 1 Genomes molecular evolution. Phylogenetic trees; procedures to build phylogenetic trees (UPGMA, NJ, MP, ML metods). Revising the human mutation rate: approaches to estimate genome mutation rates; evolution of the estimation parameters of evolution rate and revision of evolutionary divergences in humans. Evolutionary dynamics of Eukaryotic gene order: non-random organization of gene order; mechanisms governing co- expression and linkage in Eukaryotic genes. • 2 Regulation of Eukaryotic gene expression. Main mechanisms of gene expression regulation. Transcriptional programs and pluripotent/differentiated cells. Mutations in regulatory regions and pathological phenotypes. Mutations in splicing and related pathology. Dynamics of genome accessibility: procedure used to assess accessibility to genomic regions; factors affecting nucleosome occupancy; variations in chromatin structure. Regulatory sequences: approaches for their identification; relationships among predicted and in vivo regulatory binding sites; how binding sites structure affect transcription. Enhancer: effects of epigenetic modifications on enhancer functions; chromosome conformation capture and effects of tridimensional conformations on enhancer functions. How transcription factors work: mechanisms of direct and indirect mechanisms of transcription factor cooperativity; enhancers activity models; enhancers dynamic changes during progression of cellular development; synergic and hierarchical cooperation in enhancer function. Molecular mechanisms of stress transcriptional response: transcriptional reprogramming in stress response; activation and repression of genes in esponse to stress. • 3 Epigenetics. Main epigenetic modifications in DNA and histones. Writers and readers. Non-coding RNAs. DNA methylation patterns in plant and animals: de novo methylation in mammals and plants (epigenetic processes in the germinal lineages); maintaining CG methylation patterns in animals and plants and CHG in plants; active and passive DNA demethylation. RNA-mediated epigenetic regulation of gene expression: small-RNA guided DNA methylation in plants and yeast. Epigenetic regulation of cellular differentiation: epigenetic landscape of embryonic stem (ES) cells and differentiation-related modifications; chromatin modifications during embryo pre-implantation development; chromatin pre-patterning for lineage specification; stability of chromatin modifications. • 4 Genome editing. Available editing systems (ZFNs, TALENs, CRISPR/CAS9, Prime editing); DSB repairing pathways in DNA editing; details about how CRISPR/CAS9 works and its origin; examples of CRISPR/CAS9 applications in plants; evolution and additional applications of CRISPR/CAS9 in genomic analyses. • 5 Cancer genetics. Cancer and cell cycle; examples of tumours originated from chromosomal rearrangements; onco-suppressors and their main functions; retroviruses and viral oncogenes; proto-oncogenes; oncogenes activating mechanisms; some indications on oncogenesis molecular bases. Cancer functional genomics, quantitative and multiplexed approaches: complexity of cancer genetic alterations; in vivo functional evaluation of tumour suppressors, oncogenes and fusion genes; multiplexed functional analyses. Heterogeneity in cancer: genetic evolution in tumours: positive, negative, punctuated evolution, bulk- and single-cell sequencing, sampling; approaches to verify selection in tumours; cancer pattern evolution and implications; evolution of resistance to treatments. Epigenetic approaches in cancer: effects of DNA methylation inhibitors (DNMTi) in epigenetic therapies; effects of DNMTi on ERVs reactivation; epigenetic therapy response pathways; CTL epigenetic reprogramming. Mechanisms of cancer resistance in longlived mammals. • 6 Nutrigenomics: polymorphisms and nutrition (transporters and membrane receptors, transduction systems, enzymes and proteins effectors and structural proteins); nutraceutics and gene expression (epigenetic effects and regulation of gene expression of several molecules with nutraceutical effect); food intolerance genetics (lactose intolerance; intolerance and sensitivity to gluten; histamine intolerance); detoxification and detoxification system. Gender mainstreaming: approaches to grant equal benefits in actions and activities for women and mens and for eliminating gender inequalities.

The course provides advanced knowledge on food safety, with particular focus on chemical and biological contamination of foods and water intended for human consumption. Chemical contamination includes pesticide residues, heavy metals, additives, and emerging contaminants, with emphasis on sources, accumulation, monitoring, and risk assessment according to national and European regulations. Biological contamination is analyzed by distinguishing between infections, toxinfections, and intoxications, with a focus on major pathogenic biological agents, recent scientific and epidemiological evidence, and prevention and control strategies. The course also covers the practical application of the HACCP system in food industries and introduces national and European food safety regulations, complemented by the analysis of selected scientific articles and case studies, to develop both theoretical and practical skills based on scientific evidence.

Food law: the relationship between European and national sources; the concept of positive law, legal principles and obligations; Regulation (EC) No 178/2002 as the General Food Law; the institutional framework, with a focus on the role of the EFSA; the legal concept of food; food safety requirements; food harmful to human health and unfit for consumption; hazard and risk; risk analysis; traceability; the alert system, product recall and withdrawal from the market; the concept of food “hygiene”; HACCP – self-control and official control; the Competent Authority and the control plan; sanctions.

1. Control of gene expression, transcriptional regulation • Review of the basic concepts of transcriptional regulation in prokaryotes • Review of the basic concepts of transcriptional regulation in eukaryotes • Chromatin and Activators • Transcriptional coactivators and corepressors • Enhanceosome • Transcriptional regulation of complex programs: the development of Drosophila and circadian regulation. • Genome and epigenome: • Epigenetic modifications: covalent modifications of histones, the histone code • Epigenetic modifications: DNA methylation 2. The control of post-transcriptional gene expression • Coordination between transcription, maturation and RNA transport: the gene expression factory • RNA and microRNA interference: physiological and pathological functions • Other coding RNAs. I long non coding RNAs 3. Techniques for the analysis of transcriptional regulation • Reporter assays • Analysis of promoters by deletion • EMSA essays • Chromatin Immuniprecipitation Assay • Analysis of the positioning of nucleosomes 4. Main applications and implications of recombinant DNA technology • Characterization of genes • Production of recombinant proteins • Production of recombinant antigens and DNA vaccines • Gene therapy 5. Analysis of gene expression and hints of bioinformatics • Northern and western blotting • Reverse-transcription- (RT) -PCR • Real time PCR • Ribonuclease protection assay • In situ hybridization • Microarrays • NGS sequencing techniques • Sequence alignment: classification, scoring systems, exact and heuristic algorithms • Algorithms of progressive multiple alignment Positional Weight Matrices and analysis of binding sites of transcription factors Gene expression analysis: class comparison. Gene expression analysis: class discovery. Ontologies and functional annotation of the genome

During the course the following topics will be illustrated, some deepened with practical exercises/experiments in the laboratory which include the preparation of a laboratory notebook and a final individual report: 1. Equipment and laboratory instrumentation, safety in the chemical - biological laboratory. Quantitative measurements in Biochemistry. The laboratory notebook and the setup of an experiment. 2. Preparation and handling of a biological sample: use and preparation of buffer solutions; cell lysis; principles of centrifugation: centrifuges, rotors, differential and density gradient centrifugation, extraction techniques. Cell cultures: primary and secondary cultures, cell lines. Methods of cell culture. 3. Molecular Biology and techniques (Nucleic Acid Structure, Genes and Genome, Nucleic Acid Function, Nucleic Acid Handling, Basic Tools and Analysis Techniques, Isolation and Separation of Nucleic Acids, Polymerase Chain Reaction (PCR), analysis of the nucleotide sequence, analysis and manipulation of gene expression (recombinant DNA and transfections), analysis of the whole human genome. 4. Protein purification techniques and analysis: structure, purification procedures, characterization and analysis of protein functions, analysis of the ionic properties of amino acids and proteins. Chromatographic techniques, electrophoretic techniques and qualitative and quantitative assays of protein (spectrophotometric methods). 5. Immunochemical techniques. Notions on antigen and antibody, monoclonal antibodies and their preparation. Immunoblotting and immunoassays. Immunoassay systems based on immunoprecipitation and labeling of antigens or antibodies with enzymes (ELISA) and (RIA). 6. Introduction to immunofluorescence, immunocytochemistry, microscopy, cytofluorimetric analysis and main applications. 7. System Biology. Basic principles of mass spectrometry: outline of proteomics and metabolomics and applications. Bioenergetics.

Circulatory system: structure and function of the cardiovascular system in vertebrates (background on invertebrates); the heart as a pump (electrical and mechanical activity of the heart), Blood vessels and circulation: blood pressure and velocity, capillaries and exchanges with tissues. Regulation and adaptations of the cardiovascular system. Respiratory system: general principles. Mechanics of respiration and diffusion of gases through respiratory surfaces. Respiratory function of blood: transport of oxygen and carbon dioxide, buffering function of blood. Nerve and chemical regulation of respiration, respiratory adjustments and muscle activity. Digestive system: functional anatomy of the alimentary canal, control of gastrointestinal function, motility, secretion and absorption in the different districts of the digestive system, concepts of energy balance and metabolism, evolution of the digestive system. Renal function: morpho functional organization, processes of filtration, absorption and secretion in the nephron, variety of tubular structures. Water and salt balance

Plant-environement interactions in a phylogenetic context. Plant interactions with some stress-inducing abiotic factors. Main environmental pollutants and their impact on plants. Basic concepts on phytoremediation. Secondary metabolism in plant-environment interactions. Biotic interactions, with special reference to plant-microbe interactions.

1. Descriptive statistics. The data. Populations and samples. Statistical variables. Graphical display of statistical variables: barplot, histograms, boxplots. Summary statistics: measures of central tendency and dispersion. 2. Probability. Definition of probability function. Conditional probability. The binomial model. The normal (Gaussian) distribution. The Poisson distribution. 3. Introduction to statistical inference. Point estimation and confidence interval for mean and variance. 4. Student's t-test 5. Linear regression. Simple linear regression. Computation of the regression line. Tests of significance of the coefficients. 6. Categorical data analysis. Chi-square goodness-of-fit tests. Contingency tables and chi-square independence test. 7. Discussion of real-data examples and case studies through the free software R.

Introduction to Wildlife Censuses: Why census animals? Definition of count or census. Absolute vs. relative censuses. Spatially exhaustive vs. sample-based censuses. Random, regular, and aggregated distributions. Sample-based censuses. Census errors. Monitoring. Bird Censuses: Distribution studies. Sample censuses (transects and point counts). Capture-Mark-Recapture methods. Methods for studying migration. Censusing Mammals, Amphibians, Reptiles, and Fish. Censusing Insects and Other Invertebrates: Active search and capture. Traps and other non-selective capture methods. Extraction and filtration from substrate. Euthanasia and preservation. Invertebrate marking techniques. GIS LABORATORY: Introduction to cartography. Base maps and thematic maps. Paper and digital formats. Introduction to Geographic Information Systems (GIS) and their applications. GIS software and introduction to QGIS. Opening QGIS: interface overview, project menu, layer panel. Working with overlapping layers. Decorations. The Piedmont Regional Technical Map (CTR). Creating a thematic map using a predefined style. Plugins and quickmapservices. Introduction to vector files. The concept of shapefiles. Map projections and geodesy; Geographic coordinate systems. Working with the attribute table. Working with point vector files. Vector file properties. Working with symbology. Categorization and graduated symbols. Labels. Creating a new vector file from scratch. Modifying the reference system of a project. EPSG codes. Reprojecting a vector file using a different reference system. Calculating coordinates in degrees and meters. Understanding UTM zones. WMS layers. Linear and polygonal vector files. Geoprocessing. Raster files: use and management of raster images. The third dimension. Geoprocessing. Field data collection using GPS and mobile apps. Naturalistic databases. Print layout. Field trips to apply the concepts and skills learned in class.

1. Control of gene expression, transcriptional regulation • Review of the basic concepts of transcriptional regulation in prokaryotes • Review of the basic concepts of transcriptional regulation in eukaryotes • Chromatin and Activators • Transcriptional coactivators and corepressors • Enhanceosome • Transcriptional regulation of complex programs: the development of Drosophila and circadian regulation. • Genome and epigenome: • Epigenetic modifications: covalent modifications of histones, the histone code • Epigenetic modifications: DNA methylation 2. The control of post-transcriptional gene expression • Coordination between transcription, maturation and RNA transport: the gene expression factory • RNA and microRNA interference: physiological and pathological functions • Other coding RNAs. I long non coding RNAs 3. Techniques for the analysis of transcriptional regulation • Reporter assays • Analysis of promoters by deletion • EMSA essays • Chromatin Immuniprecipitation Assay • Analysis of the positioning of nucleosomes 4. Main applications and implications of recombinant DNA technology • Characterization of genes • Production of recombinant proteins • Production of recombinant antigens and DNA vaccines • Gene therapy 5. Analysis of gene expression and hints of bioinformatics • Northern and western blotting • Reverse-transcription- (RT) -PCR • Real time PCR • Ribonuclease protection assay • In situ hybridization • Microarrays • NGS sequencing techniques • Sequence alignment: classification, scoring systems, exact and heuristic algorithms • Algorithms of progressive multiple alignment Positional Weight Matrices and analysis of binding sites of transcription factors Gene expression analysis: class comparison. Gene expression analysis: class discovery. Ontologies and functional annotation of the genome

Nature management: habitat and species conservation; ecological tools for measuring biodiversity. Wild population management: restocking, reintroduction. In-situ and ex-situ conservation. Management of pest species or invasive allies species. Utilization of species distribution Atlas. Extinctions, Red lists, Minimum viable populations (MVP). Biodiversity threats. Bioindicators: using species in order to assess the qualitative status of the environment: mammals, birds, invertebrates. Animal populations. Populations with disjoint distribution and metapopulation: theoretical basis and examples. The models of zoogeography. Metapopulation and landscape ecology: the landscape as a mosaic: the patch-corridor-matrix model. Conservation genetic: principles and common techniques; census and monitoring techniques with genetic tools; genetic of endangered species. Natural history museums as biobanks for the conservation of animal species. During the course there will be talks from specific experts, practical exercises to learn dedicated softwares, field trips and museum visits.

Part I: Applied Ecology. Generalities, ecosystems, energetic flow and balance, anthropogenic impact, alterations in biogeochemical cycles, acid rain, effects of acid rain, eutrophication, effects of eutrophication, greenhouse effect, global warming, climate change, biodiversity, biodiversity indexes, biodiversity loss, alterations of habitat, invasive species, species interactions, overexploitation of resources, safeguarding of biodiversity, protected parks and marine areas. Part II: Ecotoxicology and biomonitoring. General part, pollutants, types of pollutants (heavy metals, polycyclic aromatic hydrocarbons, pesticides, pcb, dioxins, PFAS, endocrine disruptors, microplastics), natural and anthropogenic sources of pollutants, transport and dispersion, matrixes, concept of toxicity, fate of a chemical compound in a biological system, transfer of pollutants along trophic chains, bioconcentration, bioaccumulation, biomagnification, intercorrelation of pollutant effects, toxicological assays, toxicity curve, toxicity thresholds. Ecotoxicological assays, bioavailability, environmental biomonitoring generalities, triad approach, bioindication, bioindicator organisms, generalities on biomarkers, lysosomal membrane destabilisation, neutral red retention assay, morphometric alterations of immune system cells, cytoskeleton modifications, antioxidant enzymes, metallothioneins, acetylcholinesterase activity, genotoxicity, micronuclei, comet assay, biomonitoring programmes, mussel watch. Part III: Analysis of environmental impacts. Italian environmental normative, environmental impact assessment, strategic environmental assessment, impact assessment , Nature Based Solutions, Ecological Risk Assessment: management objectives, conceptual model, analytical phase, risk characterisation, management phase, environmental damage, cause-effect relationships, reclamation, bioremediation. Part IV: Ecology of agricultural systems. Generalities, agroecosystem, agricultural landscapes, soil, soil profile, texture, humification, mineralisation, soil water, porosity, permeability, soil pH and temperature, unsustainable use of soil: compaction, erosion, sealing, salinisation, desertification, energy flow in agricultural systems, biotope, biocenosis, agroecosystem interactions, photosynthetic performance, fertilisers, pesticides, Biological control: history, integrated pest management, concept of biological control, use of entomophages, parasitoids, predators, microbiological control, biological control methodologies, advantages of biological control. Marine ecosystems, Sustainable aquaculture

The world of Prokaryotes. Concept of population, community and ecosystem. Growth of microorganisms in natural environment: environmental arameters affecting microbial growth. Interactions among microorganisms: competition, neutralism, commensalism, parassitism, predation, symbiosis. Microbiology of extreme environments. The soil, chemical, physical, biological characteristics. Methods available for soil analysis. Culture dependent and independent methods. The rhizosphere: PGPR and biofertilizers, biocontrol agents. Human and plant pathogenic microorganisms in the rhizosphere . Soil biodiversity. The phyllosphere: microorganisms living on the plant leaves. Human and plant pathogenic microorganisms in the phyllosphere. Suppressive soils: take all decline and fusarium wilt. The waste composting process: role of microorganisms Viable but not culturable bacteria: ecological and clinical relevance. Bioremediation and assisted phytoremediation. Quorum sensing and interspecific communication. Quorum quenching. One health paradigm and zoonosis.

During the course the following topics will be illustrated, some deepened with practical exercises/experiments in the laboratory which include the preparation of a laboratory notebook and a final individual report: 1. Equipment and laboratory instrumentation, safety in the chemical - biological laboratory. Quantitative measurements in Biochemistry. The laboratory notebook and the setup of an experiment. 2. Preparation and handling of a biological sample: use and preparation of buffer solutions; cell lysis; principles of centrifugation: centrifuges, rotors, differential and density gradient centrifugation, extraction techniques. Cell cultures: primary and secondary cultures, cell lines. Methods of cell culture. 3. Molecular Biology and techniques (Nucleic Acid Structure, Genes and Genome, Nucleic Acid Function, Nucleic Acid Handling, Basic Tools and Analysis Techniques, Isolation and Separation of Nucleic Acids, Polymerase Chain Reaction (PCR), analysis of the nucleotide sequence, analysis and manipulation of gene expression (recombinant DNA and transfections), analysis of the whole human genome. 4. Protein purification techniques and analysis: structure, purification procedures, characterization and analysis of protein functions, analysis of the ionic properties of amino acids and proteins. Chromatographic techniques, electrophoretic techniques and qualitative and quantitative assays of protein (spectrophotometric methods). 5. Immunochemical techniques. Notions on antigen and antibody, monoclonal antibodies and their preparation. Immunoblotting and immunoassays. Immunoassay systems based on immunoprecipitation and labeling of antigens or antibodies with enzymes (ELISA) and (RIA). 6. Introduction to immunofluorescence, immunocytochemistry, microscopy, cytofluorimetric analysis and main applications. 7. System Biology. Basic principles of mass spectrometry: outline of proteomics and metabolomics and applications. Bioenergetics.

Cell diversity and biological diversity. Stages in the evolution of the eukaryotic cell. Evolution of pluricellularity and differentiation. Organization of the eukaryotic cell. General principles of cellular communication. Cellular compartments and protein trafficking. Transport of molecules between the nucleus and the cytosol. Transport of proteins in mitochondria and chloroplasts. The peroxisomes. The endoplasmic reticulum. The transport from the ER to the Golgi apparatus. Endocytosis. Exocytosis. Structural elements of the cytoskeleton (microfilaments, microtubules, intermediate filaments, associated proteins). Structure and function of protein motors (myosin, dynein, kinesin). The intracellular movement. Cell movements. Cell cultures. Primary cell lines. Preparation of primary cultures. Separation and characterization of specific cell types present in a tissue. Established cell lines and / or immortalized. Biology of cultured cells (advantages and disadvantages of cell cultures) Practical approach to cell cultures. labware: aseptic techniques. Security, risks associated with the use of genetically modified organisms. The environment: substrates, culture medium, temperature, growth factors, serum types and chemical additives etc. Cell adhesion. Kinetics of growth. Methods of cell proliferation assessment. Temporary and stable transfection. The cell in microgravity. Observation of histological preparations.

Blood disorders 1)Blood physiology 2) The immune system: relevant aspects to clinical haematology 3) Bone Marrow functions andHaematopoietic stem cells including stem cell plasticity 4) Anemia I 5) Hemoglobin diserders 6) Hemoglobin disorders II 7) Other inherited RBC disorders 8) Aplastic Anemia and PNH. Myeloid cancerogenesis 9)Myelodisplastic Syndromes 10) Chronic Myeloprolipherative disorders 11) chronic Myelogenous Leukemia 12) Acute Myeloid Leukemia 13a: Lymphoid cancerogenesis Lezione 14: Antigen-driven lymphomagenesi Lezione and methods for staging and prognostication 15 Acute lymphoblastic Leukemia and NHL 16: NHL 17: HL and Chronic lymphocytic leukemia l 18: monoclonal gammopathies 19: multiple myeloma MGUS amyloidosis 20: Targeted Therapies in hematology including MoAbs 21: CAR-T cells and other cell therapies 22a: Stem cell transplantation 23: Clinical trials. Methodology and interpretation 24: Questions and Answers

Circulatory system: structure and function of the cardiovascular system in vertebrates (background on invertebrates); the heart as a pump (electrical and mechanical activity of the heart), Blood vessels and circulation: blood pressure and velocity, capillaries and exchanges with tissues. Regulation and adaptations of the cardiovascular system. Respiratory system: general principles. Mechanics of respiration and diffusion of gases through respiratory surfaces. Respiratory function of blood: transport of oxygen and carbon dioxide, buffering function of blood. Nerve and chemical regulation of respiration, respiratory adjustments and muscle activity. Digestive system: functional anatomy of the alimentary canal, control of gastrointestinal function, motility, secretion and absorption in the different districts of the digestive system, concepts of energy balance and metabolism, evolution of the digestive system. Renal function: morpho functional organization, processes of filtration, absorption and secretion in the nephron, variety of tubular structures. Water and salt balance

Disorders of lung and low respiratory tract (1CFU) Clinical manifestation of pulmonary changes. Restrictive lung diseases: aspiration, atelectasis, brochiectasia, bronchiolitis, pulmonary fibrosis, pulmonary edema and acute respiratory distress syndrome (ARDS). Obstructive pulmonary diseases: asthma and chronic obstructive pulmonary disease (COPD). Acute infectious pathology of the lower respiratory tract: pneumonia, tuberculosis, bronchitis. Disorders of the gastrointestinal tract and connected organs (1CFU) Clinical manifestation of gastrointestinal dysfunction Motility disorders (dysphagia, gastroesophageal reflux disease, hiatal hernia, pyloric stenosis, intestinal obstruction) Gastritis Peptic ulcer disease: duodenal, gastric and stress ulcers Malabsorption syndromes Inflammatory Bowel disease and irritable bowel syndrome preclinical models to study gut diseases (organoids and murine models) Liver, gallbladder and pancreas disorders Disorders of the skin (1CFU) skin immunity Atopic dermatitis and vitiligo: from the pathogenensis to the identification of therapeutic targets for the development of new drugs Disorders of the endocrine system (1CFU) Pituitary gland: pituitary adenomas, hypopituitarism and hyperpituitarism. Thyroid: hypo- and hyper-thyroidism, goiter, thyroiditis. Endocrine pancreas: etiopathogenetic aspects of diabetes mellitus. Adrenal cortex: adrenal cortical insufficiency, hyper adrenal syndromes. Adrenal medulla: pheochromocytoma. Disorders of the cardiovascular system (1CFU) Structure and function of blood vessels. Atherosclerosis (mechanisms of atherosclerotic plaque formation and clinical consequences) Hyperlipidemias Cardiocirculatory diseases: hyperemia, hemorrhagic diseases, thrombosis, embolism, ischemia, infarction, hypotension/hypertension, shock Oncology (1CFU): Neoplastic transformation, distinctive cellular and molecular traits of tumor cells carcinogenesis process Role of the immune system in oncology (Immunogenicity of tumors and cancer immunoediting) Immunotherapy Molecular mechanisms underlying the functional relationship between inflammation and tumors

1. Descriptive statistics. The data. Populations and samples. Statistical variables. Graphical display of statistical variables: barplot, histograms, boxplots. Summary statistics: measures of central tendency and dispersion. 2. Probability. Definition of probability function. Conditional probability. The binomial model. The normal (Gaussian) distribution. The Poisson distribution. 3. Introduction to statistical inference. Point estimation and confidence interval for mean and variance. 4. Student's t-test 5. Linear regression. Simple linear regression. Computation of the regression line. Tests of significance of the coefficients. 6. Categorical data analysis. Chi-square goodness-of-fit tests. Contingency tables and chi-square independence test. 7. Discussion of real-data examples and case studies through the free software R.

Part I – Instrumental Analysis Techniques. Introduction to spectroscopic techniques, electromagnetic radiation, absorption, emission, fluorescence, phosphorescence. Molecular UV-visible absorption: principles, instrumentation, and applications. Elementary techniques: introduction, flame and furnace atomic absorption, instrumentation, interference, correction methods, and applications; inductively coupled plasma, instrumentation, and applications. Chromatographic techniques: introduction, plate and velocity theory, liquid chromatography (mechanisms, instrumentation, and applications), gas chromatography (mechanisms, instrumentation, and applications). Electrophoretic techniques: capillary electrophoresis, electrophoretic and non-electrophoretic immunoprecipitation techniques, gel techniques, and applications. Performance indices of an analytical method (LOD, LOQ, recovery, dynamic and linear range, robustness, measurement uncertainty, accuracy, repeatability, etc.). Part II – Analysis of Biological Samples. Sample collection and storage methods. Analytical determinations in the clinical chemistry laboratory: electrolyte balance, trace elements, calcium, magnesium, and major cations, lipids and lipoproteins, protein metabolism, bilirubin and jaundice-related molecules, carbohydrate metabolism, bone remodeling, enzymes, circulating markers, hormones, urinalysis. Screening and confirmatory tests: sensitivity and specificity, accuracy, ROC curve. Part III – Small-group laboratory experiments. Determination of protein content using the Bradford assay. Extraction of lipids and small molecules from biological matrices. Determination of analytes in biological matrices using liquid chromatography coupled to mass spectrometry. Determination of elements in biological samples using ICP-MS and ICP-OES.

1. Control of gene expression, transcriptional regulation • Review of the basic concepts of transcriptional regulation in prokaryotes • Review of the basic concepts of transcriptional regulation in eukaryotes • Chromatin and Activators • Transcriptional coactivators and corepressors • Enhanceosome • Transcriptional regulation of complex programs: the development of Drosophila and circadian regulation. • Genome and epigenome: • Epigenetic modifications: covalent modifications of histones, the histone code • Epigenetic modifications: DNA methylation 2. The control of post-transcriptional gene expression • Coordination between transcription, maturation and RNA transport: the gene expression factory • RNA and microRNA interference: physiological and pathological functions • Other coding RNAs. I long non coding RNAs 3. Techniques for the analysis of transcriptional regulation • Reporter assays • Analysis of promoters by deletion • EMSA essays • Chromatin Immuniprecipitation Assay • Analysis of the positioning of nucleosomes 4. Main applications and implications of recombinant DNA technology • Characterization of genes • Production of recombinant proteins • Production of recombinant antigens and DNA vaccines • Gene therapy 5. Analysis of gene expression and hints of bioinformatics • Northern and western blotting • Reverse-transcription- (RT) -PCR • Real time PCR • Ribonuclease protection assay • In situ hybridization • Microarrays • NGS sequencing techniques • Sequence alignment: classification, scoring systems, exact and heuristic algorithms • Algorithms of progressive multiple alignment Positional Weight Matrices and analysis of binding sites of transcription factors Gene expression analysis: class comparison. Gene expression analysis: class discovery. Ontologies and functional annotation of the genome

The course provides an in-depth overview of cancer development at the biochemical and molecular levels, illustrating the main mechanisms of carcinogenesis and the genetic basis of tumors. Specifically: 1. Cell Proliferation and Death Mechanisms Study of the mechanisms of cell proliferation and cell death (apoptosis), and the molecular alterations of these processes involved in tumorigenesis. Tumor progression as a multistep process: temporal dynamics of tumor development, cancer stem cells, cellular transformation as a cooperative process between oncogenic mutations, mutagenic agents, and promoters. Inflammation and cancer, with a particular focus on alterations in genes (oncogenes/tumor suppressors). Key examples of tumors with mutations in oncogenes and tumor suppressors. The role of p53 in apoptosis; intrinsic and extrinsic apoptosis; necrosis. Immortalization and the telomere: mechanisms involved in cellular and tissue senescence, senescence and telomere dynamics, telomere and transformation. 2. Signal transduction in Cancer General principles of cell signaling; signaling via G protein-coupled receptors; enzyme-linked receptor signaling. Signal transduction and transformation: the role of proto-oncogenes in transformation, receptor and cytoplasmic tyrosine kinases, mechanisms of constitutive activation of signal transduction in tumors. Cytoplasmic signaling pathways controlling various tumor-related processes: the role of mitogenic signals in tumors, the Ras pathway as a key driver of transformation, with a focus on the altered MAP kinase pathway. Invasiveness and metastasis promoted by altered signaling pathways. Targeted molecular therapies. 3. Metabolic Reprogramming in Cancer Analysis of metabolic reprogramming in cancer cells as a hallmark of tumor development and a target for anticancer compounds. Metabolic plasticity, the Warburg effect, mitochondrial dysfunction and the role of mitochondria in transformation, the role of glutamine in proliferation and cell cycle regulation, alteration of NAD biosynthesis pathways, and tumor metabolism as a therapeutic target. 4. Tumor Microenvironment and Cross-Talk Mechanisms Study of cross-talk between tumor cells and the tumor microenvironment (including immune cells such as neutrophils and macrophages, adipocytes, fibroblasts, endothelial cells). Immunotherapy. Focus on malignant pleural mesothelioma as a case study of tumor–host interaction and chronic inflammatory microenvironment. 5. Therapy Resistance Mechanisms Analysis of resistance mechanisms to therapies, with a focus on metastatic melanoma as an example. A section of the lesson will also be dedicated to gender-specific oncology therapies, with a focus on both gender-related differences and cancers specific to males and females. 6. Experimental Methods and Techniques in Cancer Research Analysis of major methods and techniques used to study altered tumor processes: 2D and 3D cancer cell cultures; co-culture systems involving cancer and stromal cells, or cancer and immune cells; flow cytometry-based characterization. Cell viability assays (MTT assay, clonogenic assay). Cell motility/invasiveness assays (transwell, scratch test). Mitochondrial function, glycolysis, and oxidative stress analysis (flow cytometry, colorimetric assays), bioenergetics. Protein analysis (Western blotting, ELISA, immunostaining). RNA analysis (RT-PCR), gene overexpression (transfection), and gene silencing (RNA interference). Selected techniques will be practiced during laboratory exercises.

Writing articles Evaluation of experiments Shaping a Power Point Presenting Ideas Managing audience, voice and non verbal communication

MELE Introduction to the course: -The laboratory of Immunogenetic -Working with workspaces and cleaning policies -Wipe test -DNA extraction -HLA system -HLA and diseases -PCR-SSP -PCR-SSO -PCR-SBT -Electrophoresis on agarose gel -Transplantation of CSE -IBMDR Registry -Clean room and cryopreservation room -Guidelines of cryopreservation room -Sampling, freezing and storage of CSE -CFU-GM colony -Isolation of purified lymphoid and myeloid cells for chimerism testing -Chimerism post CSE transplant -EFI and JACIE Accreditation procedures -Data Management MAZZUCCO Introduction to the course - concepts of regenerative medicine - main elements: cells, scaffolds, biomolecules - main laboratory techniques - quality controls

Exercise: effects of physical activity on the brain, changes in metabolism. Changes in the respiratory and cardiovascular systems with examples from different sports. Effects on the excretory and reproductive systems. Dietary principles in different disciplines. Changes in the endocrine system. Thermal stress in exercise. Physical performance in female and male athletes. Hyperbarism: gas exchange, hemodynamics of deep diving. Effects of hyperbaria on the respiratory and cardiovascular systems. Gaseous mixtures in diving. Nitrogen narcosis, oxygen toxicity, decompression sickness, gas embolism. High altitude: hypoxia and hypoxemia, respiratory and cardiovascular changes. Effects of oxygen deficiency on the body. Hypoxic factor HIF-1. Oxidative stress. Adaptive response of skeletal muscle. Lactate paradox. Sleep and cognitive abilities Water balance and weight loss. Acute mountain sickness, pulmonary edema, cerebral edema. Characteristics of Andean populations. Space flights: microg simulation with parabolic flights and head-down bed. Kinetosis and vestibular changes. Proprioceptive sensitivity in space. Blood shift and consequences on cardiovascular function. Musculoskeletal impairment: functional and structural changes in bone and muscle. Mitochondrial stress. Alteration of circadian rhythm. Alterations in the microbiota and problems related to the digestive process.

Peculiarity of the crystals: crystal state and crystalline lattices. Symmetry elements and their combination. Unit cell and its repetitiveness in the three-dimensional space. Reticular planes and crystal structure. Principles of crystal growth from solution: homogeneous and heterogeneous nucleation, crystal growth. Crystal chemistry of minerals important in the human body (phosphates), constituting the human lithiasis (uric acids, urates, Ca-oxalates, phosphates, cholesterol ), human calcifications. Minerals regulated as “asbestos” and asbestiform minerals not yet regulated: their interaction with the biological medium. Techniques for the localization, identification and characterization of the crystalline phases/minerals: the optical microscope with polarizers, directions of vibrations in the crystals; the Fresnel law. Scanning Electron Microscopy with annexed chemical microanalysis system: morphological and chemical characterization. Interpretation of the EDS spectra. Micro-Raman spectroscopy: principles and application on minerals/crystals interesting in the biological field.

History of criminalistics, notes on dactyloscopy, analysis of human genetic polymorphisms, genetic typing, interpretation of single and mixed genetic profiles, comparisons with reference samples, biostatistical evaluations using validated software for forensic use for the calculation of RMP, RMNE and LR. analysis of paternity and kinship, construction of simple and complex pedigrees, biostatistical evaluations using software validated for forensic use (Familias), BPA - Bloodstain Pattern analysis technique for the reconstruction of the crime scene, the role of the technical consultant (regulations), bureaucratic steps for the legal profession, study and analysis of real cases.

Methods to identify causative genes of monogenic diseases: the example of Amyotrophic Lateral Sclerosis, linkage analysis (SOD1 gene) 2) Methods to identify causative genes of monogenic diseases: candidate gene analysis and positional cloning (TARDBP, FUS, c9orf72 genes) 3) Methods to identify causative genes of monogenic diseases: the example of Amyotrophic Lateral Sclerosis: animal models and model organisms as a starting point for investigations. Whole exome sequencing analysis in patient families and cohorts. Pathogenetic mechanisms of disease emerged from genetic investigations 4) Applications of genetics in the clinical setting: the molecular genetic test. Molecular diagnosis of ALS (Sanger, genotyping PCR repeat). Sanger tutorial presentation 5) Applications of genetics in the clinical setting: molecular diagnosis of ALS through NGS. 6) presentation of NGS data interpretation exercise Applications of genetics in the clinical setting: therapy of monogenic diseases based on genetic knowledge 7) correction and comment on NGS data interpretation exercise. 8) Applications of genetics in the NGS clinical setting and multiomic analyzes to improve the diagnostic yield 9) Introduction Multifactorial traits and pathologies: methods to identify susceptibility genes, results and biomedical applications 10) Chromosomal and structural variant diseases

Introduction to the laboratory: preparation of the material and different sterilization methods (autoclave, sterifiltration), use of biological hoods. Outline of environmental legislation and soil microbiological sampling. Extraction and isolation of soil bacteria and counting of CFU / g at three and seven days. Extraction of nitrogen-fixing bacteria on specific soil starting from the rhizosphere. Study of cell morphology and colony of isolated bacteria. Physiological activities of isolated bacteria: solubilization of phosphate in various forms and of potassium. Screening for the production of hydrolytic enzymes from isolated bacteria: protease, cellulase, amylase. Fluorescein diacetate (FDA). Identification of isolated bacteria. Microbiological analysis of water. Microbiological control in food: standards and analytical methods. Detection of lactic acid bacteria in yoghurt.

Cell culture techniques in adhesion, in suspension and in 3D. Immunofluorescence and use of the confocal microscope. Nanomedicine (nanotheranonostic systems for the diagnosis/therapy of cancer). Immunoblotting and interpretation of the results. Methods for assessing cell migration. Flow cytometry: cell cycle analysis, expression of surface antigens (e.g. stemness and tumor markers), immunophenotyping. Molecular biology techniques for the construction of chimeric cDNAs for fusion proteins. Transfections of cDNA and siRNA in eukaryotic cells. Methods for the discrimination and the evaluation of cell death and of oxidative stress. Bioinformatics software for the analysis of transcriptomics and proteomics data. Analysis of clinical data extracted from public database (TCGA) and obtaining Kaplan-meier survival curves.

The sources of Law, the Italian Constitution, constitutional laws and ordinary laws, legislative decrees, law decrees, DPCM, regulations; regional laws and decrees. Meaning of illicit, illegitimate, fault, willful misconduct. • The European Union: meaning of Regulations and Directives, with particular regard to the health, agri-food and environmental sectors. The transposition of the Directives. • The law establishing the profession of Biologist (Law 396/67) and the institution of the figure of the Junior Biologist (DPR 328/2001). • The rules of the Civil Code and the rules of the Criminal Code that affect the profession of Biologist. The meaning of illicit, illegitimate, fault, willful misconduct. • Professional fields and sectors of operation of the Biologist, the relative legislation. • The ethics of the intellectual professions. The Biologist's Code of Ethics, the general principles. • The Biologist in the Laboratory, the different types of analysis and the granting of Authorizations, Accreditations and Certifications. • The Qualification Exam for professional practice, access requirements, characteristics of the exam and type of tests.

- Definition of environmental disease and environmental risk factors. - Air pollution and its effects on human health. - Indoor pollution and chemical contaminants - Asbestos: classification, properties, distribution, exposure types, and Italian regulations. - The Casale Monferrato model. - Benign asbestos-related diseases: asbestosis, pleural plaques, pleural thickening, and pleural effusions. - Asbestos-related neoplastic diseases. - Lung cancer: etiological factors, epidemiology, and health aspects. - Skin diseases: etiological factors, epidemiology, and health aspects. - Urological cancers: etiological factors, epidemiology, and health aspects. - Heavy metals and diseases related to exposure. - Microplastics and other emerging pollutants: their impact on health.

A priori analysis of mathematical tasks Formative assessment Summative assessment and standardised tests the specialist knowledge of mathematics teachers Mathematical competences Fields of experience Mathematics and language Language and learning Principles of cooperation and mathematical knowledge Cooperation and implicatures The language of mathematics as a multimodal and multivariate system Examples of visual demonstrations Visual Salience of representations in mathematics Psychological theories of learning Sociocultural orientations, Vygotskij Difficulties in mathematics Cognitive, metacognitive and non-cognitive aspects Interpretation of difficulties Technology in Mathematics Education Software Dynamic Geometry Platforms for e-learning

The course deals with: “Metals in biological systems”: 1. Coordination Chemistry for Biologists / 2. Biochemistry for Chemistry / 3. A Brief Overview of Molecular Biology / 4. Biological Functions of Inorganic Elements / 5. Biological Ligands for Metal Ions (amino acids; proteins; macrocycles; nucleobases) / 6. Metal Assimilation and Pathways. Sodium and potassium (ion channels; ion pumps; cotransport; homeostasis); Magnesium and Calcium (adsorption and homeostasis); Iron (assimilation; storage; homeostasis); Copper (assimilation; homeostasis); Zinc (assimilation; homeostasis) / 7. Cobalamin and cobalt proteins (introduction; reactivity; enzyme classes, deficiency) / 8. Metals at the center of photosynthesis (magnesium) (introduction; light absorption; exciton transport; why Mg2+?; magnesium at the centre of PCR) / 9. The O2 Molecule: Uptake; Transport and Storage of an Inorganic Natural Product (story of the O2 molecule; hemoglobin and myoglobin; O2 transport; a lesson from Nature; delivery; hemoglobin; a cheating husband!; when something goes wrong; how to measure O2 in vivo; the oxygen paradox; other heme and iron containing systems) / 10. Copper-containing Proteins: An Alternative to Biological Iron (introduction; copper proteins type 1-3) / 11. The Bioinorganic Chemistry of the Quintessentially Toxic Metals (introduction; aluminium; chromium; lead; cadmium; mercury; arsenic; gadolinium; brief histories of toxic metals) / 12. Metal chelation in medicine (introduction; ligands and their properties; treatment of heavy metal intoxication; iron diseases; copper disease; a story of metal chelation) / 13. Biomineralization (introduction; nucleation and crystal growth; bone formation; bone regulation; teeth; gravity- or inertia-sensitive receptors). “Metals in Medicine”: introduction to inorganic medicinal chemistry, a brief account of pharmacokinetics and pharmacodynamics, general information about cancer and cancer chemotherapy strategy. Alkylating agents will be studied in detail and, in particular, metal complexes as electrophiles: mechanism of action, toxicity Pt complexes in the clinic practice, SAR rules and design of new drugs. Organometallic complexes: titanocene and arene-dichloride-ruthenium (RAPTA). Chemoresistance. Complexes activated in the tumour acidic or reductive milieu (prodrugs). Pt(IV) derivatives. Application of the concepts of "drug targeting and delivery" to Pt compounds. Active and passive targeting. EPR effect. Liposomes and lipoplatin. DNA intercalators. The triplet / singlet oxygen and ROS (reactive oxygen species): metal complexes causing oxidative damage to DNA (bleomycin activated by iron cations) and photosensitizers for photodynamic therapy (metal - porphyrins). Photoactivatable Pt(IV)-azide complexes. Metal complexes for different therapies: Au(I) complexes as antiarthritic drugs; Bi(III) compounds as anti-ulcer drugs, complexes for rapid release of nitric oxide (NO) (e.g. sodium nitroprusside) for anti-hypertensive emergencies, vanadyl derivatives as insulin mimetics for the treatment of diabetes. Malaria and ferroquine; metal compounds for tropical diseases. Basics of radiochemistry. Nuclear medicine: drugs for radiotherapy and radiodiagnostics. SPECT and 99-m Technetium. Formation, reduction and speciation of technetium. Iodine radioisotopes and thyroid. PET and fluoroglucose. BNCT and boranes. Mention to MRI. During the lessons, whenever the opportunity arises, attention will be focused on gender-related topics. In particular, nuclear medicine topics will offer insights into the figure of Marie Curie and the role of women in chemistry/science.

The course deals with: “Metals in biological systems”: 1. Coordination Chemistry for Biologists / 2. Biochemistry for Chemistry / 3. A Brief Overview of Molecular Biology / 4. Biological Functions of Inorganic Elements / 5. Biological Ligands for Metal Ions (amino acids; proteins; macrocycles; nucleobases) / 6. Metal Assimilation and Pathways. Sodium and potassium (ion channels; ion pumps; cotransport; homeostasis); Magnesium and Calcium (adsorption and homeostasis); Iron (assimilation; storage; homeostasis); Copper (assimilation; homeostasis); Zinc (assimilation; homeostasis) / 7. Cobalamin and cobalt proteins (introduction; reactivity; enzyme classes, deficiency) / 8. Metals at the center of photosynthesis (magnesium) (introduction; light absorption; exciton transport; why Mg2+?; magnesium at the centre of PCR) / 9. The O2 Molecule: Uptake; Transport and Storage of an Inorganic Natural Product (story of the O2 molecule; hemoglobin and myoglobin; O2 transport; a lesson from Nature; delivery; hemoglobin; a cheating husband!; when something goes wrong; how to measure O2 in vivo; the oxygen paradox; other heme and iron containing systems) / 10. Copper-containing Proteins: An Alternative to Biological Iron (introduction; copper proteins type 1-3) / 11. The Bioinorganic Chemistry of the Quintessentially Toxic Metals (introduction; aluminium; chromium; lead; cadmium; mercury; arsenic; gadolinium; brief histories of toxic metals) / 12. Metal chelation in medicine (introduction; ligands and their properties; treatment of heavy metal intoxication; iron diseases; copper disease; a story of metal chelation) / 13. Biomineralization (introduction; nucleation and crystal growth; bone formation; bone regulation; teeth; gravity- or inertia-sensitive receptors). “Metals in Medicine”: introduction to inorganic medicinal chemistry, a brief account of pharmacokinetics and pharmacodynamics, general information about cancer and cancer chemotherapy strategy. Alkylating agents will be studied in detail and, in particular, metal complexes as electrophiles: mechanism of action, toxicity Pt complexes in the clinic practice, SAR rules and design of new drugs. Organometallic complexes: titanocene and arene-dichloride-ruthenium (RAPTA). Chemoresistance. Complexes activated in the tumour acidic or reductive milieu (prodrugs). Pt(IV) derivatives. Application of the concepts of "drug targeting and delivery" to Pt compounds. Active and passive targeting. EPR effect. Liposomes and lipoplatin. DNA intercalators. The triplet / singlet oxygen and ROS (reactive oxygen species): metal complexes causing oxidative damage to DNA (bleomycin activated by iron cations) and photosensitizers for photodynamic therapy (metal - porphyrins). Photoactivatable Pt(IV)-azide complexes. Metal complexes for different therapies: Au(I) complexes as antiarthritic drugs; Bi(III) compounds as anti-ulcer drugs, complexes for rapid release of nitric oxide (NO) (e.g. sodium nitroprusside) for anti-hypertensive emergencies, vanadyl derivatives as insulin mimetics for the treatment of diabetes. Malaria and ferroquine; metal compounds for tropical diseases. Basics of radiochemistry. Nuclear medicine: drugs for radiotherapy and radiodiagnostics. SPECT and 99-m Technetium. Formation, reduction and speciation of technetium. Iodine radioisotopes and thyroid. PET and fluoroglucose. BNCT and boranes. Mention to MRI. During the lessons, whenever the opportunity arises, attention will be focused on gender-related topics. In particular, nuclear medicine topics will offer insights into the figure of Marie Curie and the role of women in chemistry/science.

Embryonic development of the CNS: default theory, rostro-caudal and dorso-ventral specialization factors Cell biology of the neuron. structure of nerve tissue, physiological properties of neurons and their classification, relations with glia. Functions of macro- and microglia CNS: protective structures and ventricular system. White matter and gray matter. Cortical layers. Commissural structures (corpus callosum, anterior commissure). Division into lobes. Prefrontal lobe and the Phineas Gage case. Frontal lobe and mototrial and linguistic activity. Parietal lobe: higher order cortical areas and integration of information Temporal lobe: auditory, visual functions, written and read language comprehension. Medial areas involved in behavior, memory, and emotionality Occipital lobe: visual input transduction function Midbrain: signal retransmission role and involvement in limbic system Bridge and bulb: autonomic and vegetative functions. Top-down and bottom-up retransmission pathway Spinal cord and Rexed lamination Higher cognitive mechanisms: planning, working memory, behavior, emotionality, visual-spatial and motor coordination, language Limbic system: structural componenes and functions in emotionality and addiction. Social brain Synaptic plasticity as a physiological basis of higher processes, ma n also of neurological and psychiatric disorders

Definition of medicine and the origins of man’s role of the history of medicine. From instinctive medicine to conventional medicine. In the Greek-Roman classic world. Contagiously transmitted medicine. European Middle Ages and the study of Medicine in Universities. Science revolution of the Renaissance. In the century of Galileo and Baroque medicine. Medicine in the Age of Light. Towards New Conceptions of illness. Contradictions spanning two centuries. Nineteenth-century hospitals and places of care. Heading towards the safety in surgery. The conquest of microbial theory. In the new dimension of biological knowledge. The rapport between the clinics and the labs. The social and health organization commitment. The victorious pathways of the clinic in the diagnosis and therapy. Within and outside the boundaries of medicine: mental illness since the mid-twentieth century

The nature of the cancer cell: cell proliferation, apoptosis, angiogenesis, metastasis Oncogenes and tumor suppressors. Growth factors, receptors and cancer. Telomerase. Cancer development and Darwinian evolution. Cancer stem cells. Oncogenic viruses. Immune system and cancer. The metabolism of tumors. Precision anticancer therapies. Morphology of the epithelial neoplastic cell: practical application of the definition of dysplasia. Morphology of the non-epithelial neoplastic cell: acquisition of the totipotent phenotype. Tissue morphology of malignant neoplasms. Tissue and cell morphological alterations after neoadjuvant therapy: morphological indices of therapeutic response. During the lessons, whenever the opportunity arises, we will focus on gender-related issues.