Increased pH and tumorigenicity of fibroblasts expressing a yeast proton pump

A common early response of eukaryotic cells to stimuli which activate their proliferation is an increase in intracellular pH (ref. 1). In animal cells this is caused by the activation of an Na+/H+ exchange system; in fungi and plants an H+-pumping ATPase is involved. The critical question is whether this intracellular alkalinization is merely coincident with the activation of cell proliferation or whether it is a regulatory signal. To increase intracellular pH bypassing the usual physiological stimuli (growth factors, hormones etc.) alkaline media or ammonia have been used in the past. Both approaches suffer from long-term toxicity effects and cannot be used in tumorigenic assays with whole organisms. We introduce here a more specific approach which involves expressing the gene for the yeast plasma membrane H+-ATPase in fibroblasts. The resulting cells have an elevated intracellular pH and acquire tumorigenic properties, suggesting that the yeast ATPase gene behaves as an oncogene in mammalian cells. These experiments support a crucial role of intracellular pH in the growth control of animal cells.     

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.     

Molecular machines: nanomotor rotates microscale objects

Nanomachines of the future will require molecular-scale motors that can perform work and collectively induce controlled motion of much larger objects. We have designed a synthetic, light-driven molecular motor that is embedded in a liquid-crystal film and can rotate objects placed on the film that exceed the size of the motor molecule by a factor of 10,000. The changes in shape of the motor during the rotary steps cause a remarkable rotational reorganization of the liquid-crystal film and its surface relief, which ultimately causes the rotation of submillimetre-sized particles on the film.     

Transient folding intermediates characterized by protein engineering

Kinetic experiments on engineered mutants of barnase detect an intermediate on the folding pathway and allow the mapping of the tertiary interactions of the side chains and their energetics. Many of the interactions present in the final folded state tend to be either fully formed or not formed at all in the intermediate or subsequent transition state for folding, but the hydrophobic core becomes progressively consolidated. These methods in combination with NMR provide extensive structural characterization of the folding intermediate and the sequence of events in the folding pathway.     

Systemic Analysis of the Soccer (Football) Value Chain: Learning from the Brazilian Context

Soccer (football) is identified as the most popular sport in the world with a high turnover of economic-financial resources. The different segments of the soccer (football) value chain exert mutual influence on the variables that rule the dynamics of this sector. In this sense it is necessary to identify the variables that represent the soccer (football) value chain systemically; to understand the interrelationships between these variables, the main difficulties derived from this interrelationship and to point out variables that require actions to increment the results of the soccer (football) value chain as a whole. Hence, this study applied a semi-structured questionnaire with open-ended questions about the problems and leveraging variables that exist in this sports modality. A causal linkage diagram was elaborated based on the answers to the interviews, showing the systemic structure of the soccer (football) value chain in Brazil, whose premise it is to identify the existing circularities and the possibly existing points of leverage. The systemic structure pointed to the economic participation of soccer (football) in the Gross Domestic Product as a central variable to be leveraged, which tends to synthetize the results of the joint action of the actors in this chain. Furthermore, the variables that may limit or amplify the growth were identified. The systemic structure showed that the soccer (football) commodity chain is complex because of the great number of variables and interrelationships needed to represent its dynamics. The relationship between the actors also proved to be a factor of impact on economic and social development.     

Natural history and ecological niche modelling of coastal Atyphella Olliff Larvae (Lampyridae: Luciolinae) in Vanuatu

ABSTRACT

The genus Atyphella Olliff includes several coastal species with larvae that were collected on coastal rock within the intertidal zone. Recent fieldwork in Vanuatu has expanded the distribution of these insects and begun to provide insight into how they are able to survive in such a unique environment. An ecological niche model is produced using Maxent to predict additional locations of coastal Atyphella in the South Pacific. Larval instars for the two species of Atyphella in Vanuatu are estimated using protergum shield width measurements. Additionally, submersion tests were performed on larvae to determine survivability in saltwater and freshwater environments. These data provide evidence for previously unknown aspects of their natural history that strongly suggest the species are multivoltine and spend a large portion of their larval stage in the intertidal zone.     

Cognitive? Science?

Cognitive Science is a promising field of research that deals with one of the most fundamental questions ever: how do beings know? However, despite the long and extensive tradition of the field it has not yet become an area of knowledge with scientific identity. This is primarily due to three reasons: the lack of boundaries in defining the object of study, i.e. cognition, the lack of a precise, robust and consistent scientific methodology and results, and the inner problems derived from its interdisciplinary nature. This paper presents a background review, a theoretical frame and a humble reflection on these topics in order to arouse the internal debate among readers once more.     

Delayed ageing through damage protection by the Arf/p53 pathway

The tumour-suppressor pathway formed by the alternative reading frame protein of the Cdkn2a locus (Arf) and by p53 (also called Trp53) plays a central part in the detection and elimination of cellular damage, and this constitutes the basis of its potent cancer protection activity. Similar to cancer, ageing also results from the accumulation of damage and, therefore, we have reasoned that Arf/p53 could have anti-ageing activity by alleviating the load of age-associated damage. Here we show that genetically manipulated mice with increased, but otherwise normally regulated, levels of Arf and p53 present strong cancer resistance and have decreased levels of ageing-associated damage. These observations extend the protective role of Arf/p53 to ageing, revealing a previously unknown anti-ageing mechanism and providing a rationale for the co-evolution of cancer resistance and longevity.