An idea whose time has come

A response to An idea whose time has gone by Gregory A Petsko, Genome Biology 2007, 8:107.     

Copper methanobactin: a molecule whose time has come

Copper plays a key role in the physiology of methanotrophs. One way that these bacteria meet their high copper requirement is by the biosynthesis and release of high affinity copper binding compounds called methanobactins. Recent advances in methanobactin characterization include the first crystal structure, detailed spectroscopic analyses, and studies of metal ion specificity. Methanobactin may function in copper uptake, regulation of methane monooxygenase expression, protection against copper toxicity, and particulate methane monooxygenase activity. Methanobactin can extract copper from insoluble minerals and could be important for mineral weathering. Many methanobactin properties are reminiscent of iron siderophores, suggesting a similar mechanism of handling. Methanobactin-like compounds have also been identified in yeast mitochondria, suggesting that these molecules are a more universal phenomenon.     

Application of ecological engineering principles in agriculture

To what extent modern industrialized agriculture violates the principles of ecological engineering and which changes agriculture needs to make to be consistent with these principles are discussed. The 12 ecological principles presented are used as the starting point for this discussion. For each principle it is discussed how the agriculture of today violates these principles and how relatively small changes could make the agriculture more according to ecological engineering concepts.     

The academic medical centre: an idea whose time has come.

Interdependence of faculties of medicine or health sciences and teaching hospitals is central to the academic medical centre''s three "products": education, research and clinical service. Whether a voluntary association, partnership, joint venture or single entity, the strength of the association of member institutions must lie in mutual dependency. With the potential of reducing costs and increasing effectiveness through administrative efficiency and rationalization, especially of planning and setting priorities, the academic medical centre can outstrip its individual member institutions in contributing to the solution of Canada''s present and future challenges in health care.     

Chronomodulated chemotherapy and irradiation: an idea whose time has come?

The chronomodulated delivery of systemic chemotherapy given with irradiation (chemoradiation) is driven by an understanding of: the chronobiology of normal tissue response to cytotoxic insult, chronopharmacology, and by technologic advances in vascular access and in the availability of portable programmable pumps. Since circadian variation exists in the proliferative activity of acute-reacting normal tissues like the gut and bone marrow, a potential therapeutic gain can be realized by the chronomodulated administration of S-phase chemotherapeutic agents at biological times when these normal tissues are in a different cell phase and thus relatively spared (chronotolerance). The reasons for this are complex and possibly include newly described time-keeping genes that may influence the cell cycle. Another important aspect of chronotolerance is based on chronopharmacologic behavior of S-phase chemotherapeutic radiation sensitizing agents, especially 5-fluorouracil (5-FU). In this review laboratory and clinical evidence is presented for using chronomodulated 5-FU or the topoisomerase-I inhibitor, camptothecin, when best tolerated biologically. Although the main body of this work has been accomplished with pure chemotherapy schedules, there is emerging clinical evidence this approach to treatment also applies to the application of chemoradiation. This knowledge has been exploited only recently in the clinic. These data should be viewed as a call for additional studies to investigate the precise timing of systemic chemotherapeutic radio sensitizers to ameliorate toxicity and maximize treatment effect, especially with newer and potentially more toxic chemoradiation programs.     

Emergence and development of agro-ecological engineering in China

Chinese agricultural eco-engineering is a newborn scientific field which emerged in the practices of sustainable development of agriculture. Based on the discussion of the emergence and development of China’s agricultural eco-engineering, this paper analyzes the characteristics and components of the system. As a case study, the paper introduces the application of ecotechnology and its comprehensive effect in Baiquan county, Helingjiang province, China.     

One size fits all in prostate cancer: a story tale whose time has come and gone

The touchstone to evaluate accurately the aggressiveness and invasiveness of prostate cancer is something of a holy grail in the facet of urologic oncology. Gene expression and sequencing studies have improved our interpretations of the genetic determinants of the disease but are unsuccessful in the establishment of any unified classification to improve the molecular stratification. These questions addressing failure in rational drug design are difficult to answer in the multifaceted and heterogeneous pathogenesis of prostate cancer. In this review, we have developed a roadmap of the "recalcitrant prostate cancer proteome" to recognize the aspects of prostate cancer that may be helpful in effectively translating these findings to the clinic.     

Killing cancer cells by poly-drug elevation of ceramide levels: a hypothesis whose time has come?

Many papers have shown that sphingolipids control the balance in cells between growth and proliferation, and cell death by apoptosis. Sphingosine-1-phosphate (Sph1P) and glucosylceramide (GlcCer) induce proliferation processes, and ceramide (Cer), a metabolic intermediate between the two, induces apoptosis. In cancers, the balance seems to have come undone and it should be possible to kill the cells by enhancing the processes that lead to ceramide accumulation. The two control systems are intertwined, modulated by a variety of agents affecting the activities of the enzymes in Cer-GlcCer-Sph1P interdependence. It is proposed that successful cancer chemotherapy requires the use of many agents to elevate ceramide levels adequately. This review updates current knowledge of sphingolipid metabolism and some of the evidence showing that ceramide plays a causal role in apoptosis induction, as well as a chemotherapeutic agent.     

Functionally referential signals: A promising paradigm whose time has passed

Finding the evolutionary origins of human language in the communication systems of our closest living relatives has, for the last several decades, been a major goal of many in the field of animal communication generally and primate communication specifically. 1 - 4 The so‐called “functionally referential” signals have long been considered promising in this regard, with apparent parallels with the semantic communication that characterizes language. The once‐prominent idea that functionally referential signals are word‐like, in that they are arbitrary sounds that refer to phenomena external to the caller, has largely been abandoned. 5 However, the idea that these signals may offer the strongest link between primate communication and human language remains widespread, primarily due to the fact the behavior of receivers indicates that such signals enable them to make very specific inferences about their physical or social environment. Here we review the concept of functional reference and discuss modern perspectives that indicate that, although the sophistication of receivers provides some continuity between nonhuman primate and human cognition, this continuity is not unique to functionally referential signals. In fact, because functionally referential signals are, by definition, produced only in specific contexts, receivers are less dependent on the integration of contextual cues with signal features to determine an appropriate response. The processing of functionally referential signals is therefore likely to entail simpler cognitive operations than does that of less context‐specific signals. While studies of functional reference have been important in highlighting the relatively sophisticated processes that underlie receiver behavior, we believe that the continued focus on context‐specific calls detracts from the potentially more complex processes underlying responses to more unspecific calls. In this sense, we argue that the concept of functional reference, while historically important for the field, has outlived its usefulness and become a red herring in the pursuit of the links between primate communication and human language. © 2012 Wiley Periodicals, Inc.