1795–1995: Milestones in ROS research

Summary

Oxygen (O₂)-dependent and O₂-independent antimicrobial mechanisms are used by alveolar macrophages (AM) to maintain lung sterility, but these mechanisms are underdeveloped in neonatal AM. Nitric oxide (NO^.), a more recently described antimicrobial and immunomodulating molecule, has not been studied in neonatal AM. Lavaged AM from 3-day-old, 10-day-old, maternal and adult rats were treated with or without lipopolysaccharide (LPS) and/or interferon-γ (IFN-γ) and NO^. synthase activity was measured as its L-arginine metabolites: NO₂^?, NO₃^?, and citrulline. Superoxide anion (O₂^.-) production by suspended macrophages, initiated by either opsonized zymosan or phorbol, was used as a marker of O₂-dependent antimicrobial activity. Lysozyme content of AM was measured as a component of O₂-independent antimicrobial activity. Unstimulated 3-day-old macrophages generated >10-fold more NO₂^? + NO₃^? than did 10-day-old, maternal or adult AM. Twenty hours after LPS and IFN-γ stimulation, 3-day-old AM produced > 2 times more NO₂^? and NO₃^? than did the more mature macrophages. Basal and stimulated O₂^.- release was similar among 3-day-old, 10-day-old and adult AM, while lysozyme concentrations were > 4-fold higher in adult macrophages compared to AM from 3-day-old pups. Rather than having a role in NO^.-dependent antimicrobial activity, we propose that newborn AM have amplified NO^. production to modulate their own differentiation and replication after birth. The age-dependent differences in NO^. synthase expression by AM may lend insight into the regulation of this important enzyme.     

Circular economy: A new research field?

Action to pursue the circular economy (CE) transition is burgeoning in the government and the private sector. Does this action signal that CE is a distinct field of research with a unique disciplinary identity? This article argues that CE has reached field status, through its own epistemic communities characterized by increasingly shared methodological perspectives and normative ideals, and through institutionalized knowledge development through research journals and authority structures. The recent growth of CE research points toward more contextualized and nuanced operationalizations of the concept, evidence that the field is approaching a threshold state of maturity. Drawing on observations from academic literature and discussions with researchers and experts, we trace the process by which CE has arrived at the status of a field. The article concludes with reflections on research directions.     

Single-cell research: what determines its feasibility?

A general problem in single-cell research (SCR) is whether a representative cell is picked for analysis. In many cases, it may determine feasibility of SCR. Here, using a probability approach, we analyze this problem for laser tweezers Raman spectroscopy (LTRS), a promising technique for SCR. The results suggest that two main parameters determine the success and feasibility of SCR: the probability of picking a representative cell and the number of representative cells to be picked and analyzed. Both parameters determine the number of experiments required to obtain meaningful results. The approach is verified on several particular examples of SCR.     

Cancer research:台湾科学家发现前列腺癌骨转移新机制

<正>近日,来自台北医学大学的研究人员在国际学术期刊cancer research上在线发表了一项最新研究进展,他们发现EGFR发生细胞核定位能够抑制肿瘤抑制因子mi R-1的表达,从而促进前列腺癌的骨转移。前列腺癌是一种发生在前列腺的上皮恶性肿瘤,也是男性泌尿生殖系统最常见的恶性肿瘤之一,前列腺癌是导致美国男性因癌症死亡的第二大杀手。根据一项数据调查显示,2014年美国有大约233,000名男性诊断为前列腺癌,占到新增癌症病例的27%。前列腺癌的发生受到很多因     

Future research in weight bias: What next?

The 2015 Canadian Weight Bias Summit disseminated the newest research advances and brought together 40 experts, stakeholders, and policy makers in various disciplines in health, education, and public policy to identify future research directions in weight bias. In this paper we aim to share the results of the Summit as well as encourage international and interdisciplinary research collaborations in weight bias reduction. Consensus emerged on six research areas that warrant further investigation in weight bias: costs, causes, measurement, qualitative research and lived experience, interventions, and learning from other models of discrimination. These discussions highlighted three key lessons that were informed by the Summit, namely: language matters, the voices of people living with obesity should be incorporated, and interdisciplinary stakeholders should be included.     

Biodefense research: can secrecy and safety coexist?

Over the next 10 years, the United States will spend 6 billion US dollars to develop countermeasures against biological and chemical weapons. Much of this research on highly virulent pathogens will be done in academic settings around the country. This article explores the challenges in ensuring secrecy to protect national security while accommodating the right of local communities to have access to safety information regarding select agents and laboratory-acquired infections. Secrecy has been defended as being vital for protecting national security. Problems with secrecy can include the misinterpretation of intentions, particularly in laboratories located in nuclear weapons design facilities, and the restricted access to information relevant to public health and safety. While federal select agent legislation requires laboratories to have emergency plans in place with first responders, these plans do not necessarily include public health professionals, who will be responsible for any future public health action, such as quarantine, surveillance, or mass vaccinations, in the unlikely event that a laboratory-acquired infection spreads into a community. Laboratory-acquired infections do occur, even with the best safety mechanisms in place; however, the epidemiology of the incidence and severity of these infections are not known since there is no national surveillance reporting system. Evidence suggests that many of these infections occur in the absence of an actual laboratory accident. The best emergency plans and surveillance systems are only as good as the participation and vigilance of the laboratory workers themselves. Thus, laboratory workers have a responsibility to themselves and others to report all laboratory accidents and spills, regardless how minor. In addition, they should have a lower threshold than normal in seeking medical attention when feeling ill, and their physicians should be aware of what pathogens they work with to reduce the risk of a delay in diagnosis.     

Neuroscience and education: from research to practice?

Cognitive neuroscience is making rapid strides in areas highly relevant to education. However, there is a gulf between current science and direct classroom applications. Most scientists would argue that filling the gulf is premature. Nevertheless, at present, teachers are at the receiving end of numerous 'brain-based learning' packages. Some of these contain alarming amounts of misinformation, yet such packages are being used in many schools. What, if anything, can neuroscientists do to help good neuroscience into education?     

The ESF's EuroBioFund: Sustainable research financing?: Start with networking!

EuroBioFund was set up by the European Science Foundation in 2006, with financial support from the European Commission to catalyse the development of large scale pan-European life sciences research programmes by engaging those involved in planning and funding research.     

Medical abortion: what does the research tell us?

Dr. Ellen R. Wiebe''s study of the use of methotrexate and misoprostol in combination for early termination of intrauterine pregnancy (see pages 165 to 170 of this issue) is the first Canadian study of the use of this drug combination for medical abortion. The authors compare Wiebe''s findings with those of earlier studies on methotrexate and misoprostol, as well as with European findings on the use of mifepristone with prostaglandins. The authors argue that although the methotrexate-misoprostol combination appears to be reasonably safe for the woman, the failure rate and the teratogenicity of methotrexate and misoprosol give cause for concern. The authors conclude that medical abortions ought to be offered only where there is adequate access to laboratory and surgical facilities and where losses to follow-up are systematically minimized to reduce the potential for continued pregnancy resulting in congenital abnormality.     

Carotenoids and cardiovascular disease: what research gaps remain?

PURPOSE OF REVIEW: Dietary and blood carotenoids, including alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin, and beta-cryptoxanthin, have been examined in a number of epidemiological studies in recent years for the risk of cardiovascular disease. This review assimilated the existing and recent literature on carotenoids and cardiovascular disease and considered what research gaps may remain. RECENT FINDINGS: Numerous large cohort studies have been published in largely American men and women that have examined dietary intake or blood levels of total or individual carotenoids with the risk of various cardiovascular endpoints. Overall, early, promising results have grown increasingly inconsistent over time. More recently, studies examining lycopene and lutein/zeaxanthin have offered more promising data on a possible, but not yet established, inverse association with the risk of cardiovascular disease. Recent epidemiological data on beta-cryptoxanthin and cardiovascular disease are lacking. Primary and secondary prevention trials have extensively examined beta-carotene, but not other carotenoids, for the risk of cardiovascular disease as either the primary or secondary endpoint with largely null results. More recent studies have focused on individual carotenoids in relation to cardiovascular disease and require a more careful evaluation of potential mechanisms of effect. SUMMARY: The promise of early epidemiological studies on carotenoids and cardiovascular disease paved the way to largely disappointing results from several large prevention trials of beta-carotene. Emerging recent evidence of potential cardioprotective effects for lycopene and other carotenoids besides beta-carotene in the diet and blood suggest that there is more to be learned in the story of carotenoids and both atherosclerotic progression and clinically manifested cardiovascular disease.     

Phage display: a useful tool for malaria research?

Defining the molecular intricacies of malaria pathogenesis is a vital area of medical and scientific research. Sophisticated methods have been developed to identify and characterise host-parasite interactions that are important in infection. Phage display involves the combinatorial display of proteins or peptides on the surface of bacteriophage. The technology provides an invaluable tool for screening diverse libraries for polypeptides that have a high affinity for a given target. Phage display in malaria research has proven successful, not only in mapping the protein-protein interactions that are important in Plasmodium biology, but also in the identification of molecules that might be exploited in the design of therapeutic agents or vaccines.     

Gene-knockout mice in malaria research: useful or misleading?

Gene-knockout mice have been extensively used in the study of several malaria-induced pathologies. Some investigators believe that the deficient, infected mice mimic disease aspects produced in the absence of the target gene, but others believe that the deficient mice models mainly explain the effects of compensatory, related molecules. Comparison of some of the most relevant knockout mouse studies for understanding cerebral malaria and parasitemia and their related human reports shows that gene-knockout mice are useful tools that support conclusions from human genetic studies. These mice have helped to indicate new resistance genes against human malaria and have provided valuable information about mechanisms of malaria resistance in mice.