The exon-1 peptide of huntingtin has 51 Gln repeats and produces the symptoms of Huntington's disease in transgenic mice. Aggregation of the yeast Sup35 protein into prions has been attributed to its glutamine-rich and asparagine-rich domain. Here, we show that poly- l -asparagine forms polar zippers similar to those of poly- l -glutamine. In solution at acid pH, the glutamine-rich and asparagine-rich 18-residue Sup35 peptide, rendered soluble by the addition of two aspartates at the amino end and two lysines at the carboxyl end, gives a β-sheet CD spectrum; it aggregates at neutral pH. A poly-alanine peptide D 2 A 10 K 2 gives an α-helical CD spectrum at all pHs and does not aggregate; a peptide with the sequence of the C-terminal helix of the α-chain of human hemoglobin, preceded by two aspartates and followed by two lysines, exhibits a random coil spectrum and does not aggregate either. Alignment of several β-strands with the sequence of the 42-residue Alzheimer's amyloid β-peptide shows that they can be linked together by a network of salt bridges. We also asked why single amino acid replacements can so destabilize the native structures of proteins that they unfold and form amyloids. The difference in free energy of a protein molecule between its native, fully ordered structure and an amorphous mixture of randomly coiled chains is only of the order of 10 kcal/mol. Theory shows that destabilization of the native structure by no more than 2 kcal/mol can increase the probability of nucleation of disordered aggregates from which amyloids could grow 130,000-fold.

Neurodegenerative diseases resulting from expanded repeat sequences of glutamine residues are associated with the formation of protein aggregates in the cell nuclei of the affected neurons, but whether these are pathogenic is controversial. Recent observations indicate that the ages of onset of these diseases are exponential functions of the repeat lengths and that the probability of neural death is constant with time. The only process known to us that could give rise to such behaviour is nucleation of the aggregates.

We have constructed mutants of chymotrypsin inhibitor 2 with short glutamine repeats inserted into its inhibitory loop. These mutants oligomerize when expressed in Escherichia coli. The dimer of a mutant with four glutamines now has been crystallized, and its structure has been solved by molecular replacement by using the wild-type monomer as a search model. The structure of each half of the dimer is found to be the same as that of the wild-type monomer, except around the glutamine insertion. It was proposed that the components of the oligomers are held together by hydrogen bonds between the main-chain and side-chain amides of the glutamine repeats. Instead, they appear to form by swapping domains on folding in E. coli, and the glutamine repeats connecting the components of the dimers are disordered.

In 1952, the Queen congratulated 255 people on their hundredth birthdays and 1135 couples on their sixtieth wedding anniversaries. By 1996, these numbers had risen to 5218 and 11 688, respectively. Semilogarithmic plots, normalized to constant numbers of births and marriages, show steady exponential rises in the number of centenarians with a doubling time of 11 years, and of diamond weddings with a doubling time of 19 years. An alternative plot of the numbers of those reaching a hundred between 1910 and 1990, based on registers of births and deaths and normalized to constant births, shows an annual rise of only 1% from 1910 to 1946, followed by a steady exponential rise with a doubling time of 12 years, closely matching that of 11 years derived from the Queen's figures. The exponential rise in the number of those born from 1846 onwards living to a hundred precedes by many years the general rise in the expectation of life at birth and the general drop in mortality from infectious diseases, but it coincides with the beginning of a steady rise in real wages. Another important factor may be improved medical treatment at old age from 1946 onwards.

David Keilin, born on 21 March 1887, was Lecturer in Parasitology at Cambridge University from 1925 to 1931 and Quick Professor of Biology from then until his retirement in 1954. He first distinguished himself with the discovery of the life cycles of flies whose larvae develop parasitically in animals and plants, and are themselves parasitized by micro-organisms. Keilin then made his fame with the discovery and characterization of a system of colored enzymes, the cytochromes, which turn the chemical energy gained by the combustion of foodstuffs into a form that organisms can use for growth, movement, reproduction, and even for thought. Keilin did most of his life's work at the Molteno Institute. Keilin showed lecture demonstrations and always took a special delight in projecting the porphyrin spectrum from a feather of the turaco bird. The spectroscope was his favorite instrument using which he first discovered the absorption bands of the cytochrome system in the thoracic muscle of the fly Gastrophilus intestinalis.

The unusual properties of the Root effect haemoglobins in teleost fish-which allow them to pump O-2 into their swim bladders and eyes against very high pressures-are illuminated in a new fish haemoglobin structure.

Since the beginning of the twentieth century, the world's population has increased threefold. The revolution has not only changed the size of the population; it is radically transforming its age structure and its spatial distribution, with attendant problems and contradictions. Despite measurable advances in human welfare, such as increased longevity, more than one billion people - about one third of the total population of the Third World - live in poverty, according to a recent World Bank report. Sharply diverging rates of population growth have been accompanied by increasing disparities in income and quality of life across nations. These papers examine the relationship between physical and human resources and population within this context of mass poverty, historically unprecedented population growth, and environmental deterioration. Attention focused on those resources most critical for human well-being, including soil, water, and energy, on the one hand, and education, social organization and economic management, on the other. The discussion is framed by a broad supervision into six parts, examining demographic history and global population prospects; the relationships between population and physical, biological, and human resources; human health; and human settlements. Introductory statements, including an address by Pope John Paul II, and concluding remarks draw out the common threads and point the way towards future action and research. This book originated in a study week organized by the Pontifical Academy of Sciences to bring the best available scientific evidence to bear on this complex and still inadequately explored topic. The study week brought together experts in demography and from the physical, biological, political, economic, anthropological, religious, cultural, and health sciences, to investigate past experience and observed trends. Through this multidisciplinary analysis, a reference base was assembled that is factual, amply documented, and as scientifically indisputable as possible.