Altruistic punishment in humans.

Human cooperation is an evolutionary puzzle. Unlike other creatures, people frequently cooperate with genetically unrelated strangers, often in large groups, with people they will never meet again, and when reputation gains are small or absent. These patterns of cooperation cannot be explained by the nepotistic motives associated with the evolutionary theory of kin selection and the selfish motives associated with signalling theory or the theory of reciprocal altruism. Here we show experimentally that the altruistic punishment of defectors is a key motive for the explanation of cooperation. Altruistic punishment means that individuals punish, although the punishment is costly for them and yields no material gain. We show that cooperation flourishes if altruistic punishment is possible, and breaks down if it is ruled out. The evidence indicates that negative emotions towards defectors are the proximate mechanism behind altruistic punishment. These results suggest that future study of the evolution of human cooperation should include a strong focus on explaining altruistic punishment.     

The protein-protein interaction map of Helicobacter pylori

With the availability of complete DNA sequences for many prokaryotic and eukaryotic genomes, and soon for the human genome itself, it is important to develop reliable proteome-wide approaches for a better understanding of protein function. As elementary constituents of cellular protein complexes and pathways, protein-protein interactions are key determinants of protein function. Here we have built a large-scale protein-protein interaction map of the human gastric pathogen Helicobacter pylori. We have used a high-throughput strategy of the yeast two-hybrid assay to screen 261 H. pylori proteins against a highly complex library of genome-encoded polypeptides. Over 1,200 interactions were identified between H. pylori proteins, connecting 46.6% of the proteome. The determination of a reliability score for every single protein-protein interaction and the identification of the actual interacting domains permitted the assignment of unannotated proteins to biological pathways.     

Translational control of intron splicing in eukaryotes

Most eukaryotic genes are interrupted by non-coding introns that must be accurately removed from pre-messenger RNAs to produce translatable mRNAs. Splicing is guided locally by short conserved sequences, but genes typically contain many potential splice sites, and the mechanisms specifying the correct sites remain poorly understood. In most organisms, short introns recognized by the intron definition mechanism cannot be efficiently predicted solely on the basis of sequence motifs. In multicellular eukaryotes, long introns are recognized through exon definition and most genes produce multiple mRNA variants through alternative splicing. The nonsense-mediated mRNA decay (NMD) pathway may further shape the observed sets of variants by selectively degrading those containing premature termination codons, which are frequently produced in mammals. Here we show that the tiny introns of the ciliate Paramecium tetraurelia are under strong selective pressure to cause premature termination of mRNA translation in the event of intron retention, and that the same bias is observed among the short introns of plants, fungi and animals. By knocking down the two P. tetraurelia genes encoding UPF1, a protein that is crucial in NMD, we show that the intrinsic efficiency of splicing varies widely among introns and that NMD activity can significantly reduce the fraction of unspliced mRNAs. The results suggest that, independently of alternative splicing, species with large intron numbers universally rely on NMD to compensate for suboptimal splicing efficiency and accuracy.     

Transport of the synthetic peptide DSIP through the blood-brain barrier in rabbit

The synthetic delta sleep inducing peptide (DSIP) passes the blood-brain barrier, since i.v. injection in free moving rabbits (30 nmoles/kg) significantly increases the cortical delta activity and decreases the motor activity during 5 h.     

Polarographic activity of the antitumor drug cis-dichlorodiammineplatinum (II). The effect of hydrolysis and trans-isomerization of the drug

Summary Electrochemical activities of cis-dichlorodiammineplatinum(II) (cis-DDP) and its trans isomer were studied by classical and differential pulse polarography (d.p.p.). It was shown that both isomers yielded a polarographic step or peak at about –1.6V (vs. Ag/AgCl), which corresponded to electroreduction of the complex and to catalytic hydrogen evolution. This signal was easily measurable with the aid of d.p.p. and was suitable for investigation of the extent of hydrolysis and trans-isomerization of cis-DDP leading to the formation of toxic products. The detection limit for determination of cis-DDP and its trans isomer by d.p.p. was 1×10^–6 mol/l.Acknowledgment. This work was supported in part by Lachema n.e., Brno (Czechoslovakia).     

Regional insolation forcing of late Quaternary climate change in the Southern Hemisphere

In agreement with the Milankovitch orbital forcing hypothesis it is often assumed that glacial-interglacial climate transitions occurred synchronously in the Northern and Southern hemispheres of the Earth. It is difficult to test this assumption, because of the paucity of long, continuous climate records from the Southern Hemisphere that have not been dated by tuning them to the presumed Northern Hemisphere signals. Here we present an independently dated terrestrial pollen record from a peat bog on South Island, New Zealand, to investigate global and local factors in Southern Hemisphere climate changes during the last two glacial-interglacial cycles. Our record largely corroborates the Milankovitch model of orbital forcing but also exhibits some differences: in particular, an earlier onset and longer duration of the Last Glacial Maximum. Our results suggest that Southern Hemisphere insolation may have been responsible for these differences in timing. Our findings question the validity of applying orbital tuning to Southern Hemisphere records and suggest an alternative mechanism to the bipolar seesaw for generating interhemispheric asynchrony in climate change.     

Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs): post-transcriptional drivers of cancer progression?

The insulin-like growth factor-2 mRNA-binding proteins 1, 2, and 3 (IGF2BP1, IGF2BP2, IGF2BP3) belong to a conserved family of RNA-binding, oncofetal proteins. Several studies have shown that these proteins act in various important aspects of cell function, such as cell polarization, migration, morphology, metabolism, proliferation and differentiation. In this review, we discuss the IGF2BP family’s role in cancer biology and how this correlates with their proposed functions during embryogenesis. IGF2BPs are mainly expressed in the embryo, in contrast with comparatively lower or negotiable levels in adult tissues. IGF2BP1 and IGF2BP3 have been found to be re-expressed in several aggressive cancer types. Control of IGF2BPs’ expression is not well understood; however, let-7 microRNAs, β-catenin (CTNNB1) and MYC have been proposed to be involved in their regulation. In contrast to many other RNA-binding proteins, IGF2BPs are almost exclusively observed in the cytoplasm where they associate with target mRNAs in cytoplasmic ribonucleoprotein complexes (mRNPs). During development, IGF2BPs are required for proper nerve cell migration and morphological development, presumably involving the control of cytoskeletal remodeling and dynamics, respectively. Likewise, IGF2BPs modulate cell polarization, adhesion and migration in tumor-derived cells. Moreover, they are highly associated with cancer metastasis and the expression of oncogenic factors (KRAS, MYC and MDR1). However, a pro-metastatic role of IGF2BPs remains controversial due to the lack of ‘classical’ in vivo studies. Nonetheless, IGF2BPs could provide valuable targets in cancer treatment with many of their in vivo roles to be fully elucidated.