This month in Science Roundup:
On page 841 of this week's issue of Science, a research team claims that some of the last Neandertals may have taken refuge in the dark Arctic north rather than the sunny south as archaeological evidence has indicated. At the 32,000-year-old site of Byzovaya in Russia's Polar Ural Mountains, which at 65 degrees latitude is as far north as Iceland, archaeologists found stone tools they argue are typical of those long associated with Neandertals in Europe. If Neandertals did make the tools, it would push Neandertals' range northward by 1000 kilometers, and the site would be one of the youngest claimed for Neandertals, especially since recent redating has moved many Neandertal sites earlier in time. It would also show that the cold-adapted Neandertals could survive the rigors of the Arctic.New Work Reinforces Megaquake's Harsh Lessons in Geoscience
The moment the Tohoku-Oki earthquake struck off northern Japan on 11 March, many researchers knew their expectations had been shattered. The great offshore fault could not be counted on to behave at all predictably. And using onshore observations to gauge whether an offshore fault is building toward failure has grave limitations. Now three papers published online this week in Science help show why the inevitable release of seismic energy failed to play out as expected and why monitoring from afar fell short. The papers also point to a possible huge quake to the south, closer to Tokyo. Seismologists are concerned, but they are also now acutely aware of their limitations.Fukushima Revives The Low-Dose Debate
The ongoing crisis at Japan's Fukushima Daiichi nuclear power plant has thrust several thousand of Fukushima's 2 million residents into the middle of a scientific debate about the health effects of long-term exposure to low levels of radiation. Some researchers believe even unavoidable background radiation can be a factor in causing cancer. Others argue that tiny doses of radiation are not harmful. Some scientists even claim that low doses, by stimulating DNA repair, make you healthier—an effect known as hormesis. Studies in Fukushima could help clarify the picture. But getting answers will not be easy. Radiation exposure levels for most people were elevated so minutely above background that it may be impossible to tease out carcinogenic effects from other risk factors, such as smoking or diet. That has experts wondering whether and how to carry out such studies. A population study could nevertheless pay off scientifically.Evolving Large and Complex Brains
During the Mesozoic (~250 million to 65 million years ago), two distantly related groups of reptiles—the cynodont (or mammal-like) reptiles and the coelurosaurian theropod dinosaurs—gave rise to mammals and birds, respectively. Both mammals and birds evolved brains some 10 times as large, relative to a given body weight, as those of their ancestors (1). In both groups, these brains contributed to the evolution of the ability to control body temperature (endothermy) and complex social interactions, including parental care and a reliance on learning that even involves tool use (2, 3). The size of most parts of the brain increased in birds and mammals, but the cerebral hemispheres and cerebellum, both of which are involved in sensory and motor integration, underwent particularly spectacular development (see the figure). Although mammals and birds evolved from distantly related groups of reptiles, the higher integrative centers and circuitry of their cerebral hemispheres are very similar, and comparative neurobiologists continue to vigorously debate whether these centers evolved from the same ancestral neural centers (4, 5) or from different ones (6–8). Speculation about the evolutionary steps leading to large and complex mammalian and avian brains is equally contentious and unresolved, in part because of the rarity of fossil skulls and, until recently, the need to destroy such skulls in order to expose the endocasts (casts molded by the cranial cavity). Typically, endocasts are the only record of the brain's outward appearance in a transitional form, because brains themselves are rarely fossilized.Dyscalculia: From Brain to Education
Recent research in cognitive and developmental neuroscience is providing a new approach to the understanding of dyscalculia that emphasizes a core deficit in understanding sets and their numerosities, which is fundamental to all aspects of elementary school mathematics. The neural bases of numerosity processing have been investigated in structural and functional neuroimaging studies of adults and children, and neural markers of its impairment in dyscalculia have been identified. New interventions to strengthen numerosity processing, including adaptive software, promise effective evidence-based education for dyscalculic learners.The Prion Heretic
For 30 years, Laura Manuelidis of Yale School of Medicine has rejected the dominant theory that misfolded proteins called prions are the infectious agents behind a cluster of rare, transmissible, and fatal brain diseases called transmissible spongiform encephalopathies. When first proposed by Stanley Prusiner, the theory was widely dismissed as bizarre. Biology then held that infectious disease was caused by organisms built from DNA, RNA, or both, like viruses and bacteria—something containing a nucleic acid sequence that can replicate and spread through a cell. Proteins lack these sequences. But today, Prusiner's view dominates. Manuelidis regards the protein not as the cause of infection but as a pathological reaction to it and believes that mad cow disease and others like it are triggered by viruses—although no one has found them. She's not the only prion doubter, but her voice is by far the loudest. In part that's because as a tenured professor she's safe. Her unpopularity among top prion scientists leaves her unfazed.Differences Between Tight and Loose Cultures: A 33-Nation Study
With data from 33 nations, we illustrate the differences between cultures that are tight (have many strong norms and a low tolerance of deviant behavior) versus loose (have weak social norms and a high tolerance of deviant behavior). Tightness-looseness is part of a complex, loosely integrated multilevel system that comprises distal ecological and historical threats (e.g., high population density, resource scarcity, a history of territorial conflict, and disease and environmental threats), broad versus narrow socialization in societal institutions (e.g., autocracy, media regulations), the strength of everyday recurring situations, and micro-level psychological affordances (e.g., prevention self-guides, high regulatory strength, need for structure). This research advances knowledge that can foster cross-cultural understanding in a world of increasing global interdependence and has implications for modeling cultural change.
The Hippo pathway regulates contact inhibition of cell proliferation and, ultimately, organ size in diverse multicellular organisms. Inactivation of the Hippo pathway promotes nuclear localization of the transcriptional coactivator Yap1, a Hippo pathway effector, and can cause cancer. Here, we show that deletion of aE (a epithelial) catenin in the hair follicle stem cell compartment resulted in the development of skin squamous cell carcinoma in mice. Tumor formation was accelerated by simultaneous deletion of aE-catenin and the tumor suppressor–encoding gene p53. A small interfering RNA screen revealed a functional connection between aE-catenin and Yap1. By interacting with Yap1, aE-catenin promoted its cytoplasmic localization, and Yap1 showed constitutive nuclear localization in aE-catenin–null cells. We also found an inverse correlation between aE-catenin abundance and Yap1 activation in human squamous cell carcinoma tumors. These findings identify aE-catenin as a tumor suppressor that inhibits Yap1 activity and sequesters it in the cytoplasm.
In Science Translational Medicine
Regulatory T cells (Tregs) manipulated ex vivo have potential as cellular therapeutics in autoimmunity and transplantation. Although it is possible to expand naturally occurring Tregs, an attractive alternative possibility, particularly suited to solid organ and bone marrow transplantation, is the stimulation of total T cell populations with defined allogeneic antigen-presenting cells (APCs) under conditions that lead to the generation or expansion of donor-reactive, adaptive Tregs. Here we demonstrate that stimulation of mouse CD4+ T cells by immature allogeneic dendritic cells combined with pharmacological inhibition of phosphodiesterase 3 (PDE) resulted in a functional enrichment of Foxp3+ T cells. Without further manipulation or selection, the resultant population delayed skin allograft rejection mediated by polyclonal CD4+ effectors or donor-reactive CD8+ T cell receptor transgenic T cells and inhibited both effector cell proliferation and T cell priming for interferon-? production. Notably, PDE inhibition also enhanced the enrichment of human Foxp3+ CD4+ T cells driven by allogeneic APCs. These cells inhibited T cell proliferation in a standard in vitro mixed lymphocyte assay and, moreover, attenuated the development of vasculopathy mediated by autologous peripheral blood mononuclear cells in a functionally relevant humanized mouse transplant model. These data establish a method for the ex vivo generation of graft-reactive, functional mouse and human Tregs that uses a clinically approved agent, making pharmacological PDE inhibition a potential strategy for Treg-based therapies.
IMAGE CREDITS (In order of appearance): M.TWOMBLY/SCIENCE, BLOOMBERG/GETTY IMAGES, JOHN-INGE SVENDSEN; L. SLIMAK ET AL., SCIENCE (2), MICHAEL MARSLAND/ YALE UNIVERSITY OFFICE OF PUBLIC AFFAIRS