The renaissance of mitochondrial calcium transport.

Although the capacity of mitochondria for accumulating Ca2+ down the electrical gradient generated by the respiratory chain has been known for over three decades, the physiological significance of this phenomenon has been re-evaluated only recently. Indeed, it was long believed that the low affinity of the mitochondrial Ca2+ transporters would allow significant uptake only in conditions of cellular Ca2+ overload. Conversely, the direct measurement of [Ca2+] in the mitochondrial matrix revealed major [Ca2+] increases upon agonist stimulation. In this review, we will summarize: (a) the mechanisms that allow this large response, reconciling the biochemical properties of the transporters and the large amplitude of the mitochondrial [Ca2+] rises, and (b) the biological role of mitochondrial Ca2+ signalling, that encompasses the regulation of mitochondrial function and the modulation of the spatio-temporal pattern of cytosolic [Ca2+] increases.     

The renaissance of aminoacyl-tRNA synthesis

The role of tRNA as the adaptor in protein synthesis has held an enduring fascination for molecular biologists. Over four decades of study, taking in numerous milestones in molecular biology, led to what was widely held to be a fairly complete picture of how tRNAs and amino acids are paired prior to protein synthesis. However, recent developments in genomics and structural biology have revealed an unexpected array of new enzymes, pathways and mechanisms involved in aminoacyl-tRNA synthesis. As a more complete picture of aminoacyl-tRNA synthesis now begins to emerge, the high degree of evolutionary diversity in this universal and essential process is becoming clearer.     

The renaissance of GSK3

Glycogen synthase kinase 3 (GSK3) was initially described as a key enzyme involved in glycogen metabolism, but is now known to regulate a diverse array of cell functions. The study of the substrate specificity and regulation of GSK3 activity has been important in the quest for therapeutic intervention.     

The developmental renaissance in adaptationism

From an adaptation perspective, unoccupied patches of morphological space are inferred to be empty because they are of low fitness and selected against. These inferences hinge on venturesome assumptions, because emptiness is explained by low fitness and low fitness is inferred from emptiness. Moreover, non-adaptive factors, such as developmental constraint, could also plausibly account for empty morphospace. In response, biologists increasingly study ontogeny to test the assumption that unobserved phenotypes could be produced if selection were to favor them; finding that empty space morphologies can be readily produced in development helps reject constraint and lends support to adaptive hypotheses. This developmental approach to adaptation calls on manifold techniques, including embryology, artificial selection and comparative methods. Belying their diversity, all of these methods examine the causes of empty morphospace and mark a return of development, long excluded from traditional evolutionary biology, to adaptationist practice.     

Epigenetics and the renaissance of heresy.

Classic neo-Darwinian theory is predicated on the notion that all heritable phenotypic change is mediated by alterations of the DNA sequence in genomes. However, evidence is accumulating that stably heritable phenotypes can also have an epigenetic basis, lending support to the long-discarded notion of inheritance of acquired traits. As many of the examples of epigenetic inheritance are mediated by position effects, the possibility exists that chromosome rearrangements may be one of the driving forces behind evolutionary change by exerting position effect alterations in gene activity, an idea articulated by Richard Goldschmidt. The emerging evidence suggests that Goldschmidt's controversial hypothesis deserves a serious reevaluation.     

The microbiology of mutability

Bacteria possessing elevated spontaneous mutation rates are prevalent in certain environments, which is a paradox because most mutations are deleterious. For example, cells with defects in the methyl-directed mismatch repair (MMR) system, termed mutators or hypermutators, are overrepresented in populations of bacterial pathogens, with the mutator trait hypothesized to be advantageous in the changing host enviroments faced during colonization and establishment of chronic infections. Error-prone DNA polymerases, such as polIV and polV, function in translesion DNA synthesis, a DNA damage response that ensures genome integrity with a cost of increased mutation. While the biochemical aspects of these mutability pathways are well understood, the biological impacts have received less attention. Here, an examination of bacterial mutability systems and specifically the ecological and evolutionary context resulting in the selection of these systems is carried out.     

Vaccine renaissance

Vaccines are one of the most useful and cost-effective tools for reducing the morbidity and mortality that are associated with infectious diseases. Here, Jeffrey Almond discusses the selection of articles in this Focus issue, in the context of the challenges and opportunities facing vaccine developers today.     

The renaissance of fluorescence resonance energy transfer

Recent advances in fluorescence resonance energy transfer have led to qualitative and quantitative improvements in the technique, including increased spatial resolution, distance range, and sensitivity. These advances, due largely to new fluorescent dyes, but also to new optical methods and instrumentation, have opened up new biological applications.     

The microbiology of asthma

Asthma remains an important human disease that is responsible for substantial worldwide morbidity and mortality. The causes of asthma are multifactorial and include a complex mix of environmental, immunological and host genetic factors. In addition, epidemiological studies show strong associations between asthma and infection with respiratory pathogens, including common respiratory viruses such as rhinoviruses, human respiratory syncytial virus, adenoviruses, coronaviruses and influenza viruses, as well as bacteria (including atypical bacteria) and fungi. In this Review, we describe the many roles of microorganisms in the risk of developing asthma and in the pathogenesis of and protection against the disease, and we discuss the mechanisms by which infections affect the severity and prevalence of asthma.     

The era of microbiology: a golden phoenix.

The discoveries over the last decade have demonstrated that microbiology is a central scientific discipline with practical applications in agriculture, medicine, bioremediation, biotechnology, engineering, and other fields. It is clear that the roles of microbes in nature are so diverse that the process of mining this genetic variation for new applications will continue long into the future. Moreover, the rapid rate of microbial evolution ensures that there will be no permanent solution to agricultural, medical, or environmental problems caused by microbes. These problems will demand a continual stream of creative new approaches that evolve along with the microbes. Thus, the excitement of this field will continue long into the future. However, these opportunities and imperatives demand a deep understanding of basic microbial physiology, genetics, and ecology. Major challenges that lay ahead are to impart the broad training needed to entice and enable the next generation of microbiologists, and to educate the public and government representatives about the continued and critical importance of this field for health and the economy.