Constructing optimal ultrametrics

Clique optimization (CLOPT) is a family of graph clustering procedures that construct parsimonious ultrametrics by executing a sequence of divisive and agglomerative operations. Every CLOPT procedure is associated with a distinct graph-partitioning heuristic. Seven HCS methods, a mathematical programming algorithm, and two CLOPT heuristics were evaluated on simulated data. These data were obtained by distorting ultrametric partitions and hierarchies. In general, internally optimal models yielded externally optimal models. By recovering near-optimal solutions more consistently, CLOPT2 emerged as the most robust technique.     

Orofacial somatomotor responses in the macaque monkey homologue of Broca's area

In the ventrolateral frontal lobe of the human brain there is a distinct entity, cytoarchitectonic area 44 (Broca's area), which is crucial in speech production. There has been controversy over whether monkeys possess an area comparable to human area 44. We have addressed this question in the macaque monkey by combining quantitative architectonic analysis of the cortical areas within the ventrolateral frontal region with electrophysiological recording of neuron activity and electrical intracortical microstimulation. Here we show that, immediately in front of the ventral part of the agranular premotor cortical area 6, there is a distinct cortical area that is architectonically comparable to human area 44 and that this monkey area 44 is involved with the orofacial musculature. We suggest that area 44 might have evolved originally as an area exercising high-level control over orofacial actions, including those related to communicative acts, and that, in the human brain, area 44 eventually also came to control certain aspects of the speech act.     

Sterol carrier protein-2: structure reveals function

The multiple actions of sterol carrier protein-2 (SCP-2) in intracellular lipid circulation and metabolism originate from its gene and protein structure. The SCP-x/pro-SCP-2 gene is a fusion gene with separate initiation sites coding for 15-kDa pro-SCP-2 (no enzyme activity) and 58-kDa SCP-x (a 3-ketoacyl CoA thiolase). Both proteins share identical cDNA and amino acid sequences for 13-kDa SCP-2 at their C-termini. Cellular 13-kDa SCP-2 derives from complete, posttranslational cleavage of the 15-kDa pro-SCP-2 and from partial posttranslational cleavage of 58-kDa SCP-x. Putative physiological functions of SCP-2 have been proposed on the basis of enhancement of intermembrane lipid transfer (e.g., cholesterol, phospholipid) and activation of enzymes involved in fatty acyl CoA transacylation (cholesterol esters, phosphatidic acid) in vitro, in transfected cells, and in genetically manipulated animals. At least four important SCP-2 structural domains have been identified and related to specific functions. First, the 46-kDa N-terminal presequence present in 58-kDa SCP-x is a 3-ketoacyl-CoA thiolase specific for branched-chain acyl CoAs. Second, the N-terminal 20 amino acid presequence in 15-kDa pro-SCP-2 dramatically modulates the secondary and tertiary structure of SCP-2 as well as potentiating its intracellular targeting coded by the C-terminal peroxisomal targeting sequence. Third, the N-terminal 32 amino acids form an amphipathic a-helical region, one face of which represents a membrane-binding domain. Positively charged amino acid residues in one face of the amphipathic helices allow SCP-2 to bind to membrane surfaces containing anionic phospholipids. Fourth, the hydrophobic faces of the N-terminal amphipathic a helices along with beta strands 4, 5, and helix D form a ligand-binding cavity able to accommodate multiple types of lipids (e. g., fatty acids, fatty acyl CoAs, cholesterol, phospholipids, isoprenoids). Two-dimensional 1H-15N heteronuclear single quantum coherence spectra of both apo-SCP-2 and of the 1:1 oleate-SCP-2 complex, obtained at pH 6.7, demonstrated the homogenous formation of holo-SCP-2. While comparison of the apo- and holoprotein amide fingerprints revealed about 60% of the resonances remaining essentially unchanged, 12 assigned amide residues underwent significant chemical-shift changes upon oleic acid binding. These residues were localized in three regions: the juncture of helices A and B, the mid-section of the beta sheet, and the interface formed by the region of beta strands 4, 5, and helix D. Circular dichroism also showed that these chemical-shift changes, upon oleic acid binding, did not alter the secondary structure of SCP-2. The nuclear magnetic resonance chemical shift difference data, along with mapping of the nearby hydrophobic residues, showed the oleic acid-binding site to be comprised of a pocket created by the face of the beta sheet, helices A and B on one end, and residues associated with beta strands 4, 5, and helix D at the other end of the binding cavity. Furthermore, the hydrophobic nature of the previously ill-defined C-terminus suggested that these 20 amino acids may form a 'hydrophobic cap' which closes around the oleic acid upon binding. Thus, understanding the structural domains of the SCP-x/pro-SCP-2 gene and its respective posttranslationally processed proteins has provided new insights into their functions in intracellular targeting and metabolism of lipids.     

A nebula of gases from Io surrounding Jupiter

Several planetary missions have reported the presence of substantial numbers of energetic ions and electrons surrounding Jupiter; relativistic electrons are observable up to several astronomical units (au) from the planet. A population of energetic (>30[?]keV) neutral particles also has been reported, but the instrumentation was not able to determine the mass or charge state of the particles, which were subsequently labelled energetic neutral atoms. Although images showing the presence of the trace element sodium were obtained, the source and identity of the neutral atoms---and their overall significance relative to the loss of charged particles from Jupiter's magnetosphere---were unknown. Here we report the discovery by the Cassini spacecraft of a fast (>103[?]km[?]s-1) and hot magnetospheric neutral wind extending more than 0.5[?]au from Jupiter, and the presence of energetic neutral atoms (both hot and cold) that have been accelerated by the electric field in the solar wind. We suggest that these atoms originate in volcanic gases from Io, undergo significant evolution through various electromagnetic interactions, escape Jupiter's magnetosphere and then populate the environment around the planet. Thus a 'nebula' is created that extends outwards over hundreds of jovian radii.     

Sequence of a cDNA clone encoding human preproinsulin-like growth factor II

The insulin-like growth factors (IGF) I and II are single-chain serum proteins of 70 and 67 amino acids, respectively, which are synthesized by the liver and possibly other tissues. They are probably required for normal fetal and postnatal growth and development. They also stimulate the growth of cultured cells, possibly by controlling the progression through the G1 phase of the cell cycle. In contrast to IGF-II whose concentration does not vary during postnatal development, the serum levels of IGF-I increase several-fold to adult levels during puberty. The serum concentration of IGF-I is a sensitive monitor of growth hormone levels and is decreased in individuals with growth hormone deficiency and elevated in those with growth hormone-secreting tumours. As a first step in studying the biosynthesis of these proteins and elucidating their role(s) in normal development and in tumorigenesis, we have isolated and sequenced cDNAs prepared from adult human liver mRNA which encode the precursors to IGF-I and -II. We report here the sequence of a cDNA encoding a 180-amino acid protein which is the precursor to IGF-II.