In This Issue
APPLIED PHYSICAL SCIENCES
Human disease and gene network reveals the role of peripheral proteins
Human diseases can be caused by a variety of genetic mutations. Some diseases, such as Tay-Sachs, result from different mutations in a single gene, whereas other diseases, such as Zellweger syndrome, are caused by a mutation in any one of multiple genes. Kwang-Il Goh et al. investigated how human genetic disorders and their corresponding disease genes relate to each other at a higher level of cellular organization. The authors obtained lists of disorders, disease genes, and their associations from the Online Mendelian Inheritance in Man database, compiling information on 1,286 disorders and 1,777 disease genes. Starting froma bipartite “diseasome” graph, they generated two network projections: a human disease network that connected disorders to each other that share a common disease gene and a disease gene network that connected genes together that are associated with a common disorder. Generally, cancers were caused by somatic genetic mutations in essential or housekeeping genes. However, most inherited disease genes localized to the functional periphery of the network, with mutations preferentially in nonessential genes. — F.A.
Part of the human diseasome map.
“The human disease network” by Kwang-Il Goh, Michael E. Cusick, David Valle, Barton Childs, Marc Vidal, and Albert-László Barabási (see pages 8685–8690)
CHEMISTRY, BIOPHYSICS
Modeling motor proteins
Understanding and modeling the dynamics of single-molecule motors and other protein machines is an important facet of bio- and nanotechnology, as these tiny motors do not function in the same way as their larger counterparts. Yuichi Togashi and Alexander Mikhailov report on their model of the dynamic behavior of the F1-ATPase and myosin motor proteins, focusing on the proteins' cycle of excitation and relaxation. Taking into account discrete additions of energy that change the protein's conformation, followed by relaxation to its ground state, the authors found that these proteins always relax along a well defined trajectory. The proteins followed this trajectory when starting from different states and resisted external perturbations, properties that are not characteristic of random elastic networks. Using evolutionary optimization and these design principles, the authors developed an artificial elastic network that operates as a cyclic machine powered by ligand binding. — P.D.
An elastic network prototype of a molecular machine.
“Nonlinear relaxation dynamics in elastic networks and design principles of molecular machines” by Yuichi Togashi and Alexander S. Mikhailov (see pages 8697–8702)
ANTHROPOLOGY, MATHEMATICS
Wave-of-advance spreads hitchhiking traits
Initially developed to describe the spread of advantageous genes into a population, the wave-of-advance model can be adaptedto describe the uptake of any desirable technology through a population, such as the arrival of farming in Neolithic Europe. Cultural traits without intrinsic advantages that exist alongside the advantageous one, language for example, often get carried along, and the traits become coupled within a population. Graeme Ackland et al. adopted a wave-of-advance model to study the propagation of food production and farming in heterogeneous landscapes: Europe, the Indian subcontinent, and southern Africa. Two geographical boundaries affect the wave: a permanent subsistence boundary that results when land is too poor to be farmed and a temporary diffusion boundary that occurs because the population is not sufficiently dense. The first boundary helps identify crucial times and places where localized events can have major historical ramifications. The second boundary can allow the technology to decouple from the culture, helping establish a permanent boundary between distinct cultures with the same technology, such as the Basque region in Spain. The authors show that, although they are out-competed by farmers, hunter–gatherers live longer and eat better. Thus, modern day humans have already evolved to become bigger and stronger than their underfed, post-Neolithic counterparts. — F.A.
European scenario of wave model.
“Cultural hitchhiking on the wave of advance of beneficial technologies” by Graeme J. Ackland, Markus Signitzer, Kevin Stratford, and Morrel H. Cohen (see pages 8714–8719)
IMMUNOLOGY
Regulatory T cell deficiency causes scurfiness in mice
Regulatory T cells (Treg) play an essential role in the prevention of pathological immune responses, including autoimmunity, inflammation, and allergy. The Foxp3 forkhead transcription factor regulates the development and function of Treg, and a Foxp3 mutation has been identified in a fatal autoimmune syndrome that develops in scurfy (sf) mice. However, Foxp3 inactivation in nonhematopoietic tissues such as the thymus is thought to be necessary for the syndrome to develop. Noriko Komatsu and Shohei Hori demonstratethat the autoimmune pathology observed in sf mice results from a Treg deficiency alone. Lethally irradiated wild-type animals transplanted with sf bone marrow cells failed to develop the autoimmune disease because radioresistant host Foxp3+ Treg survived and controlled sf T cells. Mice depleted of radioresistant host Treg succumbed to the disease when transplanted with sf cells. In nonhematopoietic cells, the sf mutation was unable to cause the autoimmune syndrome and did not affect T cell development and homeostasis. The radioresistant host T cells fully reconstituted the Treg pool in the absence of new Treg production, demonstrating the robust homeostatic mechanism that controls the Treg pool. — F.A.
Hematoxylin and eosin staining of tissue sections.
“Full restoration of peripheral Foxp3 + regulatory T cell pool by radioresistant host cells in scurfy bone marrow chimeras” by Noriko Komatsu and Shohei Hori (see pages 8959–8964)
