Rise and fall of political complexity in island South-East Asia and the Pacific

There is disagreement about whether human political evolution has proceeded through a sequence of incremental increases in complexity, or whether larger, non-sequential increases have occurred. The extent to which societies have decreased in complexity is also unclear. These debates have continued largely in the absence of rigorous, quantitative tests. We evaluated six competing models of political evolution in Austronesian-speaking societies using phylogenetic methods. Here we show that in the best-fitting model political complexity rises and falls in a sequence of small steps. This is closely followed by another model in which increases are sequential but decreases can be either sequential or in bigger drops. The results indicate that large, non-sequential jumps in political complexity have not occurred during the evolutionary history of these societies. This suggests that, despite the numerous contingent pathways of human history, there are regularities in cultural evolution that can be detected using computational phylogenetic methods.     

A PPARγ-FGF1 axis is required for adaptive adipose remodelling and metabolic homeostasis

Although feast and famine cycles illustrate that remodelling of adipose tissue in response to fluctuations in nutrient availability is essential for maintaining metabolic homeostasis, the underlying mechanisms remain poorly understood. Here we identify fibroblast growth factor 1 (FGF1) as a critical transducer in this process in mice, and link its regulation to the nuclear receptor PPARγ (peroxisome proliferator activated receptor γ), which is the adipocyte master regulator and the target of the thiazolidinedione class of insulin sensitizing drugs. FGF1 is the prototype of the 22-member FGF family of proteins and has been implicated in a range of physiological processes, including development, wound healing and cardiovascular changes. Surprisingly, FGF1 knockout mice display no significant phenotype under standard laboratory conditions. We show that FGF1 is highly induced in adipose tissue in response to a high-fat diet and that mice lacking FGF1 develop an aggressive diabetic phenotype coupled to aberrant adipose expansion when challenged with a high-fat diet. Further analysis of adipose depots in FGF1-deficient mice revealed multiple histopathologies in the vasculature network, an accentuated inflammatory response, aberrant adipocyte size distribution and ectopic expression of pancreatic lipases. On withdrawal of the high-fat diet, this inflamed adipose tissue fails to properly resolve, resulting in extensive fat necrosis. In terms of mechanisms, we show that adipose induction of FGF1 in the fed state is regulated by PPARγ acting through an evolutionarily conserved promoter proximal PPAR response element within the FGF1 gene. The discovery of a phenotype for the FGF1 knockout mouse establishes the PPARγ–FGF1 axis as critical for maintaining metabolic homeostasis and insulin sensitization.     

生物标记物之警示信号

寻找生物标记——能对阿尔茨海默氏症的侵入发出警告信号的标记物——的工作一直在进行着。而开展这项研究的目的旨在赢得对这一疾病治疗的主动权．探索阿尔茨海默氏症防治的新模式     

Assortative mating in soldier beetles (Cantharidae: Chaulignathus ): test of the mate-choice hypothesis

Soldier beetles of 2 species, Chauliognathus basalis and C. deceptus , were examined to test the Crespi hypothesis that positive assortative mating by size is caused by mate choices. Specifically, we tested the prediction that if mate choice involves choosing the largest mate available, then mating individuals will be larger than nonmating individuals. Four samples were taken, at different times during the mating season, from each of 2 sites. Each sample consisted of mating pairs, nonmanting males, and nonmating females. Some of the samples contained beetles of both species; others contained beetles of a single species. For each gender elytron lengths of mating individuals were compared with elytron lengths of nonmating individuals. We found no effect of mating status (mating vs. nonmating) on elytron lengths in samples that exhibited assertive mating (which occurs where 2 species coexist). Surprisingly, we found a consistent effect of mating status on elytron lengths in samples that did not exhibit assortative mating (which occurs where only 1 species exists). Our results do not support the mate-choice hypothesis. Instead, mate choice and assortative mating appear to be alternative mating patterns in which mate choice occurs where a single species exists and assortative mating occurs where 2 species coexist.     

The quantum liar experiment in Cramer's transactional interpretation

Cramer's Transactional Interpretation (TI) is applied to the “quantum liar experiment” (QLE). It is shown how some apparently paradoxical features can be explained naturally, albeit nonlocally (since TI is an explicitly nonlocal interpretation, at least from the vantage point of ordinary spacetime). At the same time, it is proposed that in order to preserve the elegance and economy of the interpretation, it may be necessary to consider offer and confirmation waves as propagating in a “higher space” of possibilities.     

Self-incompatibility in Papaver targets soluble inorganic pyrophosphatases in pollen

In higher plants, sexual reproduction involves interactions between pollen and pistil. A key mechanism to prevent inbreeding is self-incompatibility through rejection of incompatible ('self') pollen. In Papaver rhoeas, S proteins encoded by the stigma interact with incompatible pollen, triggering a Ca2+-dependent signalling network resulting in pollen tube inhibition and programmed cell death. The cytosolic phosphoprotein p26.1, which has been identified in incompatible pollen, shows rapid, self-incompatibility-induced Ca2+-dependent hyperphosphorylation in vivo. Here we show that p26.1 comprises two proteins, Pr-p26.1a and Pr-p26.1b, which are soluble inorganic pyrophosphatases (sPPases). These proteins have classic Mg2+-dependent sPPase activity, which is inhibited by Ca2+, and unexpectedly can be phosphorylated in vitro. We show that phosphorylation inhibits sPPase activity, establishing a previously unknown mechanism for regulating eukaryotic sPPases. Reduced sPPase activity is predicted to result in the inhibition of many biosynthetic pathways, suggesting that there may be additional mechanisms of self-incompatibility-mediated pollen tube inhibition. We provide evidence that sPPases are required for growth and that self-incompatibility results in an increase in inorganic pyrophosphate, implying a functional role for Pr-p26.1.     

Targeting C-reactive protein for the treatment of cardiovascular disease

Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new cardioprotective and neuroprotective treatments. We have previously shown that human C-reactive protein (CRP), the classical acute-phase protein that binds to ligands exposed in damaged tissue and then activates complement, increases myocardial and cerebral infarct size in rats subjected to coronary or cerebral artery ligation, respectively. Rat CRP does not activate rat complement, whereas human CRP activates both rat and human complement. Administration of human CRP to rats is thus an excellent model for the actions of endogenous human CRP. Here we report the design, synthesis and efficacy of 1,6-bis(phosphocholine)-hexane as a specific small-molecule inhibitor of CRP. Five molecules of this palindromic compound are bound by two pentameric CRP molecules, crosslinking and occluding the ligand-binding B-face of CRP and blocking its functions. Administration of 1,6-bis(phosphocholine)-hexane to rats undergoing acute myocardial infarction abrogated the increase in infarct size and cardiac dysfunction produced by injection of human CRP. Therapeutic inhibition of CRP is thus a promising new approach to cardioprotection in acute myocardial infarction, and may also provide neuroprotection in stroke. Potential wider applications include other inflammatory, infective and tissue-damaging conditions characterized by increased CRP production, in which binding of CRP to exposed ligands in damaged cells may lead to complement-mediated exacerbation of tissue injury.     

Vigorous exchange between the Indian and Atlantic oceans at the end of the past five glacial periods

The magnitude of heat and salt transfer between the Indian and Atlantic oceans through 'Agulhas leakage' is considered important for balancing the global thermohaline circulation. Increases or reductions of this leakage lead to strengthening or weakening of the Atlantic meridional overturning and associated variation of North Atlantic Deep Water formation. Here we show that modern Agulhas waters, which migrate into the south Atlantic Ocean in the form of an Agulhas ring, contain a characteristic assemblage of planktic foraminifera. We use this assemblage as a modern analogue to investigate the Agulhas leakage history over the past 550,000 years from a sediment record in the Cape basin. Our reconstruction indicates that Indian-Atlantic water exchange was highly variable: enhanced during present and past interglacials and largely reduced during glacial intervals. Coherent variability of Agulhas leakage with northern summer insolation suggests a teleconnection to the monsoon system. The onset of increased Agulhas leakage during late glacial conditions took place when glacial ice volume was maximal, suggesting a crucial role for Agulhas leakage in glacial terminations, timing of interhemispheric climate change and the resulting resumption of the Atlantic meridional overturning circulation.     

Closing gaps in the human genome with fosmid resources generated from multiple individuals

The human genome sequence has been finished to very high standards; however, more than 340 gaps remained when the finished genome was published by the International Human Genome Sequencing Consortium in 2004. Using fosmid resources generated from multiple individuals, we targeted gaps in the euchromatic part of the human genome. Here we report 2,488,842 bp of previously unknown euchromatic sequence, 363,114 bp of which close 26 of 250 euchromatic gaps, or 10%, including two remaining euchromatic gaps on chromosome 19. Eight (30.7%) of the closed gaps were found to be polymorphic. These sequences allow complete annotation of several human genes as well as the assignment of mRNAs. The gap sequences are 2.3-fold enriched in segmentally duplicated sequences compared to the whole genome. Our analysis confirms that not all gaps within 'finished' genomes are recalcitrant to subcloning and suggests that the paired-end-sequenced fosmid libraries could prove to be a rich resource for completion of the human euchromatic genome.