Promoter regions of many neural- and nutrition-related genes have experienced positive selection during human evolution

Surveys of protein-coding sequences for evidence of positive selection in humans or chimpanzees have flagged only a few genes known to function in neural or nutritional processes, despite pronounced differences between humans and chimpanzees in behavior, cognition and diet. It may be that most such differences are due to changes in gene regulation rather than protein structure. Here, we present the first survey of promoter (5'-flanking) regions, which are rich in cis-regulatory sequences, for evidence of positive selection in humans. Our results indicate that positive selection has targeted the regulation of many genes known to be involved in neural development and function, both in the brain and elsewhere in the nervous system, and in nutrition, particularly in glucose metabolism.     

The MAP test for multimodality

We introduce a test for detecting multimodality in distributions based on minimal constrained spanning trees. We define a Minimal Ascending Path Spanning Tree (MAPST) on a set of points as a spanning tree that has the minimal possible sum of lengths of links with the constraint that starting from any link, the lengths of the links are non-increasing towards a root node. We define similarly MAPSTs with more than one root. We present some algorithms for finding such trees. Based on these trees, we devise a test for multimodality, called the MAP Test (for Minimal Ascending Path). Using simulations, we estimate percentage points of the MAP statistic and assess the power of the test. Finally, we illustrate the use of MAPSTs for determining the number of modes in a distribution of positions of galaxies on photographic plates from a rich galaxy cluster.     

Plasma enteroglucagon,peptide YY and gastrin in rats deprived of luminal nutrition,and after urogastrone-EGF administration. A proliferative role for PYY in the intestinal epithelium?

Intestinal tissue mass was significantly reduced throughout the gastrointestinal tract (p<0.001) of=" intravenously=" fed=" (tpn)=" rats.=" urogastrone-epidermal=" growth=" factor,=" (uro-egf),=" reversed=" these=" changes.=" although=" plasma=" enteroglucagon=" and=" gastrin=" levels=" showed=" a=" small=" increase=" with=" uro-egf,=" this=" was=" far=" less=" than=" the=" gut=" tissue=" weight=" change,=" suggesting=" that=" it=" was=" unlikely=" that=" they=" were=" involved=" in=" modulating=" the=" proliferative=" response=" of=" the=" intestine=" to=" uro-egf.=" peptide=" tyrosine=" tyrosine=" (pyy)=" levels=" were=" however=" significantly=" increased=" by=" uro-egf,=" indicating=" that=" pyy=" may=" possibly=" have=" a=" role=" in=" the=" modulation=" of=" intestinal=" cell=">We thank the Cancer Research Campaign for their financial assistance and acknowledge the technical assistance of Mr W. Lenton.     

The naturalism of the sciences

The sciences are characterized by what is sometimes called a “methodological naturalism,” which disregards talk of divine agency. In response to those who argue that this reflects a dogmatic materialism, a number of philosophers have offered a pragmatic defense. The naturalism of the sciences, they argue, is provisional and defeasible: it is justified by the fact that unsuccessful theistic explanations have been superseded by successful natural ones. But this defense is inconsistent with the history of the sciences. The sciences have always exhibited what we call a domain naturalism. They have never invoked divine agency, but have always focused on the causal structure of the natural world. It is not the case, therefore, that the sciences once employed theistic explanations and then abandoned them. The naturalism of the sciences is as old as science itself.     

Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis

Most tumors exhibit increased glucose metabolism to lactate, however, the extent to which glucose-derived metabolic fluxes are used for alternative processes is poorly understood. Using a metabolomics approach with isotope labeling, we found that in some cancer cells a relatively large amount of glycolytic carbon is diverted into serine and glycine metabolism through phosphoglycerate dehydrogenase (PHGDH). An analysis of human cancers showed that PHGDH is recurrently amplified in a genomic region of focal copy number gain most commonly found in melanoma. Decreasing PHGDH expression impaired proliferation in amplified cell lines. Increased expression was also associated with breast cancer subtypes, and ectopic expression of PHGDH in mammary epithelial cells disrupted acinar morphogenesis and induced other phenotypic alterations that may predispose cells to transformation. Our findings show that the diversion of glycolytic flux into a specific alternate pathway can be selected during tumor development and may contribute to the pathogenesis of human cancer.     

A linguistic model for the rational design of antimicrobial peptides

Antimicrobial peptides (AmPs) are small proteins that are used by the innate immune system to combat bacterial infection in multicellular eukaryotes. There is mounting evidence that these peptides are less susceptible to bacterial resistance than traditional antibiotics and could form the basis for a new class of therapeutic agents. Here we report the rational design of new AmPs that show limited homology to naturally occurring proteins but have strong bacteriostatic activity against several species of bacteria, including Staphylococcus aureus and Bacillus anthracis. These peptides were designed using a linguistic model of natural AmPs: we treated the amino-acid sequences of natural AmPs as a formal language and built a set of regular grammars to describe this language. We used this set of grammars to create new, unnatural AmP sequences. Our peptides conform to the formal syntax of natural antimicrobial peptides but populate a previously unexplored region of protein sequence space.     

Superfluid helium: visualization of quantized vortices

When liquid helium is cooled to below its phase transition at 2.172 K, vortices appear with cores that are only ?ngstr?ms in diameter, about which the fluid circulates with quantized angular momentum. Here we generate small particles of solid hydrogen that can be used to image the cores of quantized vortices in their three-dimensional environment of liquid helium. This technique enables the geometry and interactions of these vortices to be observed directly.     

Transforming Self and Society: A "Critical Appreciation" Model

This paper sets out to uncover some relationships between reflection, discourse and action. By challenging and synthesizing some polemical arguments concerning the creation, maintenance, and transformation of self and society, a model of self-society dynamics that operates through reflection, discourse, and action is developed. The model of self-society dynamics brings together aspects of self-reflection and ideology-critique (explored in the paper), which it is suggested are required for any intervention (transformative action) to be grounded in locally meaningful ways. By creating a dialog community in which self- and group assumptions can be subjected to validation through discourse, it is proposed that a dynamic balance between individual needs and broader societal aims may be achieved. If individuals can be open to such discourse (i.e., they can become critically self-reflective), then it is argued that possibilities for achieving sustainable change will be significantly enhanced.