Forty-five years of split-brain research and still going strong

Forty-five years ago, Roger Sperry, Joseph Bogen and I embarked on what are now known as the modern split-brain studies. These experiments opened up new frontiers in brain research and gave rise to much of what we know about hemispheric specialization and integration. The latest developments in split-brain research build on the groundwork laid by those early studies. Split-brain methodology, on its own and in conjunction with neuroimaging, has yielded insights into the remarkable regional specificity of the corpus callosum as well as into the integrative role of the callosum in the perception of causality and in our perception of an integrated sense of self.     

The dauer hypothesis and the evolution of parasitism: 20 years on and still going strong

How any complex trait has evolved is a fascinating question, yet the evolution of parasitism among the nematodes is arguably one of the most arresting. How did free-living nematodes cross that seemingly insurmountable evolutionary chasm between soil dwelling and survival inside another organism? Which of the many finely honed responses to the varied and harsh environments of free-living nematodes provided the material upon which natural selection could act? Although several complementary theories explain this phenomenon, I will focus on the dauer hypothesis. The dauer hypothesis posits that the arrested third-stage dauer larvae of free-living nematodes such as Caenorhabditis elegans are, due to their many physiological similarities with infective third-stage larvae of parasitic nematodes, a pre-adaptation to parasitism. If so, then a logical extension of this hypothesis is that the molecular pathways which control entry into and recovery from dauer formation by free-living nematodes in response to environmental cues have been co-opted to control the processes of infective larval arrest and activation in parasitic nematodes. The molecular machinery that controls dauer entry and exit is present in a wide range of parasitic nematodes. However, the developmental outputs of the different pathways are both conserved and divergent, not only between populations of C. elegans or between C. elegans and parasitic nematodes but also between different species of parasitic nematodes. Thus the picture that emerges is more nuanced than originally predicted and may provide insights into the evolution of such an interesting and complex trait.     

Problems with the use of cladistic analysis in palaeoanthropology

Cladistic analysis is a popular method for reconstructing evolutionary relationships on the human lineage. However, it has limitations and hidden assumptions that are often not considered by palaeoanthropologists. Some researchers who are opposed to its use regard cladistics as the preferred method for taxonomic «splitters» and claim it has lead to a revitalisation of typology. Typology remains a part of human evolutionary studies, regardless of the acceptance or use of cladistics. The assumption/preference for «splitting» over «lumping» in cladistics (alpha) taxonomy and the general failure to evaluate (post-hoc) such taxonomies have served to reinforce this assertion.

Researchers have also adopted a number of practices that are logically untenable or introduce considerable error. The evolutionary trend of human encephalisation, apparently isometric with body size, and concurrent reduction in the gut and masticatory apparatus, suggests continuous cladistic characters are biased by problems of body size.

The method suffers a logical weakness, or circularity, leading to bias when characters with multiple states are used. Coding of such characters can only be done using prior criteria, and this is usually done using an existing phylogenetic scheme. Another problem with coding character states is the handling of variation within species. While this form of variation is usually ignored by palaeoanthropologists, when characters are recognised as varying, their treatment as a separate state adds considerable error to cladograms.

The genetic proximity of humans, chimpanzees and gorillas has important implications for cladistic analyses. It is argued that chimpanzees and gorillas should be treated as ingroup taxa and an alternative outgroup such as orangutans should be used, or an (hypothetical) ancestral body plan developed. Making chimpanzees and gorillas ingroup taxa would considerably enhance the biological utility of anthropological cladograms.

All published human cladograms fail to meet standard quality criteria indicating that none of them may be considered reliable. The continuing uncertainty over the number and composition of fossil human species is the largest single source of error for cladistics and human phylogenetic reconstruction.     

Forty years of research on the assembly and infection process of bacteriophage

This short biographical note was written as part of the lead-in material for a festschrift kindly organized for me on the occasion of my 70th birthday. The collection of articles assembled in this issue range within the spectrum of the topics covered in the special issue ‘Multiscale structural biology—biophysical principles and practice ranging from biomolecules to bionanomachines.’ Here I describe some of the high points of my 40 years of research science conducted in the USA, Switzerland and Japan. I also use this opportunity to express my sincerest thanks to my former colleagues and the very many contributors who so kindly contributed to this special issue.     

Pfam 10 years on: 10,000 families and still growing

Classifications of proteins into groups of related sequences are in some respects like a periodic table for biology, allowing us to understand the underlying molecular biology of any organism. Pfam is a large collection of protein domains and families. Its scientific goal is to provide a complete and accurate classification of protein families and domains. The next release of the database will contain over 10,000 entries, which leads us to reflect on how far we are from completing this work. Currently Pfam matches 72% of known protein sequences, but for proteins with known structure Pfam matches 95%, which we believe represents the likely upper bound. Based on our analysis a further 28,000 families would be required to achieve this level of coverage for the current sequence database. We also show that as more sequences are added to the sequence databases the fraction of sequences that Pfam matches is reduced, suggesting that continued addition of new families is essential to maintain its relevance.     

Forty years of amino acid transmission in the brain.

This article is concerned with the discovery that amino acids, particularly L-glutamate and gamma-aminobutyrate (GABA), are central neurotransmitters. The crucial observations that lead to the conclusion that these two amino acids produce most of the synaptic excitation and inhibition in the central nervous system, were made in late 1950's. The combination of neurochemical knowledge and improved electrophysiological techniques was paramount in making these discoveries possible. In particular, the use of specific antagonists in microiontophoretic experiments provided the most decisive evidence. The relationship is also explored between these early findings and those of the present era characterised by extensive use of techniques of molecular biology and the development of drugs against targets identified 30 to 40 years ago.     

Problems and perspectives of palaeoanthropology in India

In recent years the importance and meaning of palaeoanthropology have gained a sharper focus. The scope of palaeoanthropological research in India is promising, and this is perhaps one of the few ideal places where the whole spectrum of the study of this discipline can be set forth, both in biological and cultural aspects. The present paper takes it to span the period from the beginning of the process of human evolution during the late Tertiary period to the surviving primitive communities. The relevant biological data in the form of fossil remains have been found only for the earliest stage, pre-Pleistocene. Afterwards, up to the end of the Pleistocene, there is no positive evidence of human skeletal remains, which are obtained only from post-Pleistocene onwards. In this subcontinent, the emphasis for a significant stretch of the human evolutionary process is thus almost exclusively on the cultural traits which, however, play a dominant role. An attempt has been made to suggest a tentative frame-work of bio-cultural evolution in India. In this context, reference has been made also to the relevance of studying the primitive communities of the recent period.     

Forty years of stress research: principal remaining problems and misconceptions.

An overview of the main problems and misconceptions in the clinical application and theoretic evaluation of the stress concept reveals that the same 10 problems appear to cause the greatest difficulties in its application, irrespective of the specialty in which it is used: (1) the correct definition of stress, stressors and the general adaptation syndrome; (2) the concept of nonspecificity in biology and medicine; (3) the conditioning of stress responses by diverse endogenous (mainly genetically determined) and exogenous (environmental) factors; (4) the relation between the genral and the local adaptation syndromes; (5) the difference between direct and indirect pathogens; (6) the definition of the morbid lesions in whose pathogenesis stress plays a particularly prominent role--the so-called diseases of adaptation; (7) the role of genetics versus that of factors under voluntary self-control in mastering biologic stress; (8) the mode of action of syntoxic and catatoxic hormones, drugs and behavioural attitudes; (9) the so-called first mediator of the stress response, which carries the message that a state of stress exists from the directly affected area to the neurohormonal regulatory centres; and (10) the prophylaxis and treatment of stress-induced damage by pharmacologic and behavioural techniques.     

Forty years of achievement in French research on digestive physiology in the pig.

The contribution of the research group set up by Rérat in the early 1960s in Jouy-en-Josas, and then expanded to Rennes, is summarised. As digestive processes are a major key to the nutritional status of monogastric animals, original methodologies based on advanced experimental surgery were developed in the pig to quantify the digestion and absorption yield, to know their factors of variation, and to understand their physiological and nutritional consequences. The group also extended its expertise to the control of food intake, the role of the nervous system and regulatory peptides, and several biomedical gut-related topics.