A simple technique for the measurement of3H- and14C-radioactivity per μg DNA in fixed tissue

Summary A simple, rapid and versatile technique for scintillation counting of double labelled fixed tissue is described. Furthermore, DNA determination can be performed on the same tissue digest.The financial support of the Norwegian Research Council for Science and the Humanities and the skillful technical assistance of Mr A. Vonheim are gratefully acknowledged.     

Free choice activates a decision circuit between frontal and parietal cortex

We often face alternatives that we are free to choose between. Planning movements to select an alternative involves several areas in frontal and parietal cortex that are anatomically connected into long-range circuits. These areas must coordinate their activity to select a common movement goal, but how neural circuits make decisions remains poorly understood. Here we simultaneously record from the dorsal premotor area (PMd) in frontal cortex and the parietal reach region (PRR) in parietal cortex to investigate neural circuit mechanisms for decision making. We find that correlations in spike and local field potential (LFP) activity between these areas are greater when monkeys are freely making choices than when they are following instructions. We propose that a decision circuit featuring a sub-population of cells in frontal and parietal cortex may exchange information to coordinate activity between these areas. Cells participating in this decision circuit may influence movement choices by providing a common bias to the selection of movement goals.     

Insights into hominid evolution from the gorilla genome sequence

Gorillas are humans' closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evidence consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 million years ago. In 30% of the genome, gorilla is closer to human or chimpanzee than the latter are to each other; this is rarer around coding genes, indicating pervasive selection throughout great ape evolution, and has functional consequences in gene expression. A comparison of protein coding genes reveals approximately 500 genes showing accelerated evolution on each of the gorilla, human and chimpanzee lineages, and evidence for parallel acceleration, particularly of genes involved in hearing. We also compare the western and eastern gorilla species, estimating an average sequence divergence time 1.75 million years ago, but with evidence for more recent genetic exchange and a population bottleneck in the eastern species. The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution.     

Perception of three-dimensional structure from motion in monkey and man

Information on motion is important for the determination of the three-dimensional (3-D) structure of the environment for both human and non-human primates. For example, if a person were to close one eye and look at an evenly illuminated, irregularly shaped object, he would be unlikely to guess its shape correctly. But if the object is moved about, the correct shape immediately becomes apparent. Little is known about how the primate visual system actually does this, although various theories have been proposed. We have developed novel, highly controlled motion stimuli to use with psychophysical and physiological techniques to study how 3-D structure is obtained from motion. We show that the Rhesus monkey can detect 3-D structure from motion in the same way as human subjects. Furthermore, the dependence of both species on certain parameters of the display shows that information is integrated both spatially and temporally for this higher visual function.     

Postsynaptic long-term potentiation follows coupling of dendritic glutamate application and synaptic activation

Summary Dendritic depolarization, which seems to be involved in the induction of long-term potentiation (LTP), was elicited by localized glutamate application. When paired to low frequency synaptic activation in the same area, the subsequent changes had features in common with LTP, expressed as an increased probability of firing and shorter spike latency. The EPSP was not significantly increased.     

Common nonsynonymous variants in PCSK1 confer risk of obesity

Mutations in PCSK1 cause monogenic obesity. To assess the contribution of PCSK1 to polygenic obesity risk, we genotyped tag SNPs in a total of 13,659 individuals of European ancestry from eight independent case-control or family-based cohorts. The nonsynonymous variants rs6232, encoding N221D, and rs6234-rs6235, encoding the Q665E-S690T pair, were consistently associated with obesity in adults and children (P = 7.27 x 10(-8) and P = 2.31 x 10(-12), respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity.     

Many sequence variants affecting diversity of adult human height

Adult human height is one of the classical complex human traits. We searched for sequence variants that affect height by scanning the genomes of 25,174 Icelanders, 2,876 Dutch, 1,770 European Americans and 1,148 African Americans. We then combined these results with previously published results from the Diabetes Genetics Initiative on 3,024 Scandinavians and tested a selected subset of SNPs in 5,517 Danes. We identified 27 regions of the genome with one or more sequence variants showing significant association with height. The estimated effects per allele of these variants ranged between 0.3 and 0.6 cm and, taken together, they explain around 3.7% of the population variation in height. The genes neighboring the identified loci cluster in biological processes related to skeletal development and mitosis. Association to three previously reported loci are replicated in our analyses, and the strongest association was with SNPs in the ZBTB38 gene.     

SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations

We conducted a genome-wide association study using 207,097 SNP markers in Japanese individuals with type 2 diabetes and unrelated controls, and identified KCNQ1 (potassium voltage-gated channel, KQT-like subfamily, member 1) to be a strong candidate for conferring susceptibility to type 2 diabetes. We detected consistent association of a SNP in KCNQ1 (rs2283228) with the disease in several independent case-control studies (additive model P = 3.1 x 10(-12); OR = 1.26, 95% CI = 1.18-1.34). Several other SNPs in the same linkage disequilibrium (LD) block were strongly associated with type 2 diabetes (additive model: rs2237895, P = 7.3 x 10(-9); OR = 1.32, 95% CI = 1.20-1.45, rs2237897, P = 6.8 x 10(-13); OR = 1.41, 95% CI = 1.29-1.55). The association of these SNPs with type 2 diabetes was replicated in samples from Singaporean (additive model: rs2237895, P = 8.5 x 10(-3); OR = 1.14, rs2237897, P = 2.4 x 10(-4); OR = 1.22) and Danish populations (additive model: rs2237895, P = 3.7 x 10(-11); OR = 1.24, rs2237897, P = 1.2 x 10(-4); OR = 1.36).     

Small mammals within riparian habitats of a regulated and unregulated arid land river

In northwestern Colorado, flow regulation on the Green River has created a transitional plant community that features encroachment by upland vegetation into cottonwood ( Populus fremontii )-dominated, riparian forest on topographically high floodplain sites and reduced cottonwood regeneration on low floodplain sites. To assess how these changes might have affected small mammal distributions, in 1994 and 1995 we live-trapped during periods surrounding spring flooding at 3 sites: above and below the confluence of the regulated Green River and at the ecologically similar, but unregulated, Yampa River (reference site). More species were captured at the most regulated site along the Green River above its confluence with the Yampa River. Within sites, more species were captured in riparian habitats than adjacent upland habitats. Despite river regulation-induced habitat changes, we did not detect changes in species distributions within low and high floodplain habitat for Peromyscus maniculatus or Microtus montanus , but changes may have occurred for Dipodomys ordii . The total effect of regulation-induced habitat change on small mammal populations may not be fully revealed until current, mature cottonwood forests disappear and associated woody debris decomposes.     

Categorization, anomalies and the discovery of nuclear fission

The characteristics of scientific revolutions and by the same token the question of which events in the history of science deserve the name of revolutionary are controversial themes in the philosophy of science. An issue of disagreement is the question of whether or not events in which only parts of a paradigm are overthrown can truly be called a revolution, or if this term is to be reserved for the developments in which a wholesale replacement of ideas takes place. In this paper Kuhn's latest attempt to state a principle for distinguishing revolutionary developments will be reviewed, and it will be argued that certain developments entailing only partial replacements of the paradigm can be called revolutionary. The discovery of fission will serve as case study to illustrate this idea.