PREFACE ........................................................ 11
GENERAL INTRODUCTION ........................................... 21
FIRST PART THE FABULOUS DESTINY OF BIOLOGY
1.1. HISTORICAL OVERVIEW ....................................... 25
1.1.1. The vision of the ancients ......................... 25
1.1.2. The naturalist epic and experimental physiology .... 27
1.1.3. In search of a unifying formalism of life
(enzymes, metabolisms, bioenergetics) .............. 31
1.2. MOLECULAR BIOLOGY AND ITS ACHIEVEMENTS .................... 35
1.2.1. Molecular biology of the gene (double helix, gene
expression and regulation, the "Central Dogma") .... 35
DNA and the double helix ........................... 35
Gene function and regulation (initial concepts) .... 38
1.2.2. The genetic code - The transfer of genetic
information: transcription and translation ......... 39
Messenger RNA and the genetic code ................. 42
Protein synthesis .................................. 43
1.2.3. Gene regulation - The repressor - The lactose
operon ............................................. 44
1.2.4. The central dogma of molecular biology ............. 46
1.3. GENETIC ENGINEERING - BASIC CONSEQUENCES - APPLICATIONS ... 49
1.3.1. Genetic engineering - Discovery - Biology of
higher organisms ................................... 49
1.3.2. Exons-Introns ...................................... 50
1.3.3. Splicing ........................................... 51
1.3.4. Ribozymes and the world of RNAs .................... 52
1.4. THE COMPLEXITY OF GENETIC MATERIAL IN "EUKARYOTES" ........ 55
1.4.1. Chromatin compaction - Nucleosomes ................. 55
1.4.2. Epigenetic modifications ........................... 55
1.4.3. Positive regulation - Promoters - Cis-regulatory
sequences .......................................... 56
1.4.4. Coding and non-coding DNA .......................... 58
1.4.5. Repetitive elements ................................ 59
1.5. GENOMICS - GENERAL DATA - CONSEQUENCES - APPLICATIONS ..... 61
1.5.1. Structural and functional genomics ................. 62
The "surprises" of genomics - The number of
genes .............................................. 62
1.5.2. Genetic Polymorphism - SNP ......................... 64
1.5.3. A Biology of molecular networks: transcriptomes -
proteomes .......................................... 66
Transcriptomes - DNA chips ......................... 66
Proteomes .......................................... 67
Protein interaction ................................ 69
From genome to phenome ............................. 70
1.5.4. What is a gene? Systems biology .................... 71
1.6. A NEW INSPIRATION IN MOLECULAR BIOLOGY - THE WORLD
OF RNAs AND THE PHENOMENA OF INTERFERENCE - THE RETURN
OF EPIGENETICS ............................................ 73
1.6.1. The world of RNAs .................................. 73
1.6.2. Si-RNA and micro-RNA ............................... 74
Formation - Transport and matching of micro-RNA
(Drosha, Exportine, Dicer and Rise) ................ 75
Applications ....................................... 78
1.6.3. The return of epigenetics - When heterodoxy
becomes a symbol of openness ....................... 79
DNA Methylation .................................... 80
Transcriptional repression of transposons .......... 81
Parental imprinting (differential expression of
certain genes of paternal or maternal origin) ...... 81
Inactivation of the X chromosome ................... 82
Histone modification and the role of histone
variants in epigenetic control ..................... 83
1.7. FROM CONTEMPORAY BIOLOGY TO THE CHALLENGES OF
DEVELOPMENT ............................................... 87
1.7.1. Reflections on contemporary biology ................ 87
1.7.2. What can sciences do for a sustainable
development? The role of biology ................... 89
1.7.3. Health ............................................. 90
1.7.4. Agriculture ........................................ 91
1.7.5. Environment - Biodiversity - Evolution ............. 92
1.7.6. Conclusion ......................................... 93
SECOND PART BIOLOGY AND THE GREAT DEVELOPMENTAL CHALLENGES
2.1. HEALTH .................................................... 97
2.1.1. Infectious diseases (the revival of microbiology,
vaccines, diagnosis and anti-viral therapy,
zoonoses, prion diseases) .......................... 97
2.1.1.1. The return of infectious diseases -
Diseases of poverty - Neglected tropical
diseases .................................. 97
2.1.1.2. Microbiology and its revival .............. 99
General considerations .................... 99
Factors in microbiology revival .......... 100
Genomics and virulence ................... 101
Target cells and the penetration
mechanisms of pathogenic bacteria ........ 102
Susceptibility genes ..................... 104
Environment and reservoirs of
pathogenic agents ........................ 104
2.1.1.3. Vaccinology .............................. 106
Historical insights and generalities ..... 106
Different types of vaccination ........... 107
The challenges posed by AIDS, malaria
and tuberculosis ......................... 109
2.1.1.4. Zoonoses ................................. 110
AIDS (the HIV virus) ..................... 111
SARS ..................................... 112
Ebola .................................... 113
Chikungunya .............................. 113
Avian flu ................................ 113
Marburg, West Nile ....................... 114
Recent studies ........................... 114
2.1.1.5. Diagnosis and therapy of viral diseases
- An overview ............................ 116
Antiviral therapies ...................... 117
2.1.1.6. Prion diseases ........................... 119
The "prion" protein PrPsc ................ 119
Prion diseases ........................... 121
2.1.2. Genetic diseases - Gene therapy ................... 124
2.1.2.1. Historical aspects ....................... 125
2.1.2.2. The example of Duchenne muscular
dystrophy (DMD) - A school case .......... 126
2.1.2.3. Neurological affections .................. 128
2.1.2.4. Susceptibility Genes - Polymorphisms
and diseases - HLA genes ................. 129
HLA system and predisposition to
diseases ................................. 130
Susceptibility genes and SNP-type
polymorphisms ............................ 131
2.1.2.5. Gene therapy - The gene as a drug and
gene surgery ............................. 131
The work of A. Fischer and M. Cavazzana
Calvo .................................... 132
The strategy of exon skipping ............ 133
2.1.2.6. Children's diseases and
congenital malformations ........ 134
2.1.3. Stem cells and cell therapy (a hope in the field
of degenerative diseases) ......................... 135
2.1.3.1. Developmental biology considerations ..... 135
2.1.3.2. Adult Stem Cells ......................... 137
Blood stem cells ......................... 137
Other types of adult stem cells .......... 138
Neural Stem Cells ........................ 139
"Plasticity" of Adult Stem Cells ......... 140
2.1.3.3. Embryonic Stem Cells ..................... 140
Historical aspects ....................... 141
Discovery of human embryonic stem cells
and potential applications ............... 141
Risks .................................... 143
Somatic nuclear transfer (therapeutic
cloning) - Reproductive cloning in
animals .................................. 144
2.1.3.4. Ethical aspects of the use of embryonic
stem cells ............................... 145
2.1.4. Ageing - Senescence and cell death (apoptosis) -
Cancers ........................................... 146
2.1.4.1. Ageing - General Considerations .......... 146
2.1.4.2. Genetics and longevity ................... 148
Relationships between genomics and
longevity in the human species ........... 151
The causes of physiological ageing ....... 152
Molecular ageing - effects of free
radicals ................................. 153
2.1.4.3. Cellular senescence ...................... 154
2.1.4.4. Apoptosis - programmed cell death ........ 154
2.1.4.5. Apoptosis and Cancer ..................... 157
2.1.4.6. Molecular mechanisms of apoptosis ........ 159
2.1.4.7. Cancers .................................. 161
Epidemiological facts .................... 161
Cancers in the world and their growing
incidence in the developing countries .... 162
Biology of cancer - oncogenes -
suppressor genes - repair system ......... 165
Sentinel genes ........................... 166
Repair systems and cancers ............... 167
Epigenetic factors ....................... 169
Epigenetic control of differentiation
in cancer stem cells ..................... 169
2.2. AGRICULTURE - NUTRITION - FEEDING MANKIND - THE
CHALLENGES OF MALNUTRITION - TRANSGENIC PLANTS (DATA,
HOPES AND FEARS) ......................................... 173
2.2.1. Feeding mankind - Data on the problem and the
challenges to be met .............................. 173
2.2.1.2. A world food crisis - The "return of
hunger" .................................. 177
2.2.2. Contributions of genomics ......................... 179
2.2.3. Transgenic plants - Some general data ............. 180
Principal types of modification introduced by
plant transgenesis with agricultural aims ......... 181
Drought and salinity .............................. 181
Other characteristics ............................. 184
Overall physiology - Nutritional value ............ 186
Plant transgenesis and health ..................... 187
Hopes - Reservations - Potential risks ............ 189
2.2.4. Livestock as a major component of human
nutrition - environmental effects and
perspectives ...................................... 192
Research .......................................... 193
Livestock and environment ......................... 194
Association between Agriculture and Animal
Farming ........................................... 195
2.3. ENVIRONMENT - ENERGY - BIODIVERSITY ...................... 197
2.3.1. Energy challenges - Greenhouse effects -
Renewable energies - Biofuels ..................... 197
2.3.1.1. Energy challenges - Climate change ....... 197
2.3.1.2. Non- CO2 emitting energy sources ......... 199
2.3.1.3. Renewable energies ....................... 200
Photovoltaic ............................. 200
Biomass .................................. 200
"Fuel versus food" ....................... 201
Second-generation biofuels ............... 202
2.3.2. Biodiversity ...................................... 202
2.3.2.1. Identifying and protecting
biodiversity ............................. 202
2.3.2.1.1. General data - Threats and
concerns for a common
heritage ...................... 202
The effects of global
warming ....................... 204
Urbanisation, deforestation,
extensive agriculture ......... 204
International attitudes and
measures ...................... 205
2.3.2.1.2. The variety of living
species - An unfinished
investigation ................. 205
2.3.2.1.3. Phylogenetic relations -
Genomic comparisons ........... 207
The Archaea - The appearance
of eukaryotes ................. 208
2.3.2.1.4. Plant Genomics and
Biodiversity .................. 209
2.3.2.1.5. Animal Genomics and
Biodiversity .................. 211
2.3.2.1.6. Biodiversity of
microorganisms -
Metagenomics .................. 211
CONCLUSION .................................................... 215
BIBLIOGRAPHY .................................................. 219
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