Early-stage romantic love can induce euphoria, is a cross-cultural phenomenon, and is possibly a developed form of a mammalian drive to pursue preferred mates. It has an important influence on social behaviors that have reproductive and genetic consequences. To determine which reward and motivation systems may be involved, we used functional magnetic resonance imaging and studied 10 women and 7 men who were intensely "in love" from 1-17 months. Participants alternately viewed a photograph of their beloved and a photograph of a familiar individual, interspersed with a distraction-attention task. Group activation specific to the beloved under the two control conditions occurred in dopamine-rich areas associated with mammalian reward and motivation, namely the right ventral midbrain and three regions of the right caudate nucleus. Activation in the left ventral tegmental area was correlated with facial attractiveness scores. Activation in the right medial caudate was correlated with questionnaire scores that quantified intensity of romantic passion. In the left insula-putamen-globus pallidus, activation correlated with trait affect intensity. The results suggest that romantic love uses subcortical reward and motivation systems to focus on a specific individual, that limbic cortical regions process individual emotion factors, and that there is localization heterogeneity for reward functions in the human brain.
As a reader of this journal you are probably a professional scientist with an interest in communicating the importance of what you do to the world at large. We share that interest, and advertise to journalists the work we publish that we feel most likely to be of general interest, via press releases on the EurekAlert! website. This works very well, and papers in Current Biology are frequently covered in the general media.
This is all fine and dandy; good for us, our authors, the science journalists and their readers.... There is an aspect of this process that is, I believe, deadly serious and of the utmost importance. In certain areas of science, public understanding has an influence on behaviour with serious consequences — this is especially true of medical and environmental matters.
We have detected two paralogs of the tRNA endonuclease gene of Methanocaldococcus jannaschii in the genome of the crenarchaeote Sulfolobus solfataricus. This finding has led to the discovery of a previously unrecognized oligomeric form of the enzyme. The two genes code for two different subunits, both of which are required for cleavage of the pre-tRNA substrate. Thus, there are now three forms of tRNA endonuclease in the Archaea: a homotetramer in some Euryarchaea, a homodimer in other Euryarchaea, and a heterotetramer in the Crenarchaea and the Nanoarchaea. The last-named enzyme, arising most likely by gene duplication and subsequent "subfunctionalization," requires the products of both genes to be active.
Evolutionary biologists agree that gene duplication has played an important role in the history of life on Earth, providing a supply of novel genes that make it possible for organisms to adapt to new environments (1). The existence of diverse multigene families, particularly in eukaryotes, provides evidence that numerous events of gene duplication followed by functional diversification have shaped genomes as we know them. But it is less certain how this panoply of new functions actually arises, leaving room for ingenious speculation but not much rigor. Cases where we can reconstruct with any confidence the evolutionary steps involved in the functional diversification are relatively few. Thus the report in this issue of PNAS by Tocchini-Valentini and colleagues (2) on tRNA endonucleases of Archaea is particularly welcome as a concrete example of how new protein functions can arise.
A recent study by Dasgupta et al., 2005 used a genome-wide RNAi screen in Drosophila cells to identify 238 candidate regulators of the Wnt-signaling pathway, most of which had not been previously connected to Wnt signaling. Supporting in vivo studies are in progress. The fact that such an impressive number of potential modulators had eluded detection in genetic screens underscores the potential of applying new, high-throughput approaches to old problems.
In this issue of Developmental Cell, Reddien et al. describe the first large-scale RNAi screen in freshwater planarians, classic models for regeneration studies. Their work paves the way for a detailed understanding of regeneration and tissue maintenance in these fascinating animals.
A secreted cysteine protease (CP) fraction from Trichomonas vaginalis is shown here to induce apoptosis in human vaginal epithelial cells (HVEC) and is analyzed by mass spectrometry. The trichomonad parasite T. vaginalis causes one of the most common non-viral sexually transmitted infection in humans, trichomoniasis. The parasite as well as a secreted cysteine protease (CP) fraction, isolated by affinity chromatography followed by Bio-Gel P-60 column chromatography, are shown to induce HVEC apoptosis, as demonstrated by the Cell Death Detection ELISAPLUS assay and Annexin V-FITC flow cytometry analyses. Initiation of apoptosis is correlated with protease activity since the specific CP inhibitor E-64 inhibits both activities. SDS-PAGE analysis of the CP fraction reveals triplet bands around 30 kDa, and MALDI-TOF MS indicates two closely associated peaks of MW 23.6 kDa and 23.8 kDa. Mass spectral peptide sequencing of the proteolytically digested CPs results in matches to previously reported cDNA clones, CP2, CP3, and CP4 [Mallinson et al. Microbiology 140 (1994) 2725-2735.], as well as another sequence with high homology to CP4 (www.tigr.org). These last two species are the most abundant components of the CP fraction. The present results, suggesting that CP induced programmed cell death may be involved in the pathogenesis of T. vaginalis infection in vivo, may have important implications for therapeutic intervention.
Bacterial DNA and synthetic oligomers containing CpG dinucleotides activate the immune system through Toll-like receptor (TLR) 9. Here, we compare the immunostimulatory activity of three immunomers with different nucleotide sequences containing a synthetic cytosine-phosphate-2'-deoxy-7-deazaguanosine dinucleotide (CpR), called immunomodulatory oligonucleotides (IMOs), in mouse, human, and monkey systems. IMOs induced IL-12 and IFN- secretion more than a control non-CpG IMO in mice. All three IMOs activated HEK293 cells expressing TLR9 but not TLR3, -7, or -8. IMOs induced human B-cell proliferation and enhanced expression of CD86 and CD69 surface markers on B cells. The three IMOs induced CD86 expression on human plasmacytoid dendritic cells, but only IMOs that contained a 5'-terminal TCR nucleotide sequence induced IFN- secretion. A sequence that forms a duplex structure also was required for IFN- induction in human peripheral blood mononuclear cell cultures. IMOs induced chemokine and cytokine gene expression in human peripheral blood mononuclear cells. In monkeys, all three IMOs induced transient changes in peripheral blood leukocytes and lymphocytes and activated B and T lymphocytes. All three IMOs induced IFN- in vivo in monkeys; the IMO sequence that forms a stable secondary structure induced the highest levels of IFN-. These studies are, to our knowledge, the first comprehensive studies to compare the activity of IMOs containing synthetic stimulatory CpR dinucleotides in mouse, monkey, and human systems. These results suggest that IMOs induce strong and rapid immunostimulation and that the CpR dinucleotide is recognized by TLR9, leading to immune-cell activation and cytokine secretion in vitro and in vivo.
Highly heterogeneous spatiotemporal patterns of maturation of the murine brain during the first 80 postnatal days were examined by high-dimensional deformation-based morphometry applied to high-resolution diffusion tensor MRIs. The maturation profile revealed a sharp contrast between tissue anisotropy changes in the cortex and in major white-matter fibers. Radially oriented tissue anisotropy was measured during the first postnatal week in cortical regions, reflecting the underlying columnar organization of the cortex. Subsequently, tissue anisotropy reduced rapidly, potentially reflecting the growth of randomly oriented dendritic trees that reduce tissue coorientation. Distinct anisotropy patterns were also observed along layer I of the cortex and were attributed to thin fibers oriented parallel to the outer surface. Last, spatially complex patterns of maturation were measured in all major axonal pathways and in the hippocampus, caudate putamen, and cerebellum. This analysis provides a framework for quantifying normative maturation patterns against which phenotypes of mice of different genetic and environmental backgrounds can be contrasted.
