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Research is a highly competitive profession where evaluation plays a central role; journals are ranked and individuals are evaluated based on their publication number, the number of times they are cited and their h -index. Yet such evaluations are often done in inappropriate ways that are damaging to individual careers, particularly for young scholars, and to the profession. Furthermore, as with all indices, people can play games to better their scores. This has resulted in the incentive structure of science increasingly mimicking economic principles, but rather than a monetary gain, the incentive is a higher score. To ensure a diversity of cultural perspectives and individual experiences, we gathered a team of academics in the fields of ecology and evolution from around the world and at different career stages. We first examine how authorship, h -index of individuals and journal impact factors are being used and abused. Second, we speculate on the consequences of the continued use of these metrics with the hope of sparking discussions that will help our fields move in a positive direction. We would like to see changes in the incentive systems, rewarding quality research and guaranteeing transparency. Senior faculty should establish the ethical standards, mentoring practices and institutional evaluation criteria to create the needed changes.

Although ribosomes are ubiquitous and essential for life, recent data indicate that monogenic causes of ribosomal dysfunction can confer a remarkable degree of specificity in terms of human disease phenotype. Box C/D small nucleolar RNAs (snoRNAs) are evolutionarily conserved non-protein-coding RNAs involved in ribosome biogenesis. Here we show that biallelic mutations in the gene SNORD118, encoding the box C/D snoRNA U8, cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts (LCC), presenting at any age from early childhood to late adulthood. These mutations affect U8 expression, processing and protein binding and thus implicate U8 as essential in cerebral vascular homeostasis., Competing Interests: The authors declare that they have no competing financial interests.

Objectives: Myocardial failure, leading to inotrope-unresponsive shock, is the predominant cause of death in meningococcal and other forms of septic shock. Proinflammatory cytokines released in septic shock are known to have myocardial depressant effects. We previously showed that interleukin 6 is a major myocardial depressant factor in children with meningococcal septicemia. In the current study, we aimed to investigate the mechanisms by which interleukin 6 induces myocardial failure in meningococcal sepsis and to identify potential novel therapeutic targets., Design: Laboratory-based study., Setting: University hospital and laboratories., Patients: Children with a clinical diagnosis of meningococcal septic shock., Methods: We studied interleukin 6-induced signaling events, both in vitro using isolated rat ventricular cardiac myocytes as a model of myocardial contractility and in whole blood from children with meningococcal sepsis., Interventions: None., Measurements and Main Results: We demonstrated involvement of Janus kinase 2, phosphatidylinositol 3-kinase, Akt, and p38 mitogen-activated protein kinase in interleukin 6-induced negative inotropy in isolated cardiac myocytes. Inhibition of p38 mitogen-activated protein kinase not only reversed interleukin 6-induced myocardial depression in both rat and human myocytes, but restored inotrope responsiveness. Cardiomyocytes transduced with dominant-negative p38 mitogen-activated protein kinase showed no interleukin 6-induced myocardial depression. To investigate p38 mitogen-activated protein kinase in vivo, we profiled global RNA expression patterns in peripheral blood of children with meningococcal septicemia. Transcripts for genes mapping to the p38 mitogen-activated protein kinase pathway showed significantly altered levels of abundance with a high proportion of genes of this pathway affected., Conclusions: Our findings demonstrate an integral role of the p38 mitogen-activated protein kinase pathway in interleukin 6-mediated cardiac contractile dysfunction and inotrope insensitivity. Dysregulation of the p38 mitogen-activated protein kinase pathway in meningococcal septicemia suggests that this pathway may be an important target for novel therapies to reverse myocardial dysfunction in patients with meningococcal septic shock who are not responsive to inotropic support.

Premise of Study: The origin of the passionflower corona, a complex series of structures between the petals and stamens, has intrigued botanists for centuries, but has proven intractable using traditional approaches. Supplementing developmental data with expression analyses of three floral identity genes, we test whether the corona in Passiflora caerulea (blue passionflower) is homologous to petals or stamens or whether an alternative hypothesis of the corona as a novel structure is supported., Methods: Corona development was investigated using scanning electron microscopy. Expression of the P. caerulea B-class genes PISTILLATA (PcPI) and TOMATO MADS6 (PcTM6), and C-class gene AGAMOUS (PcAG) was investigated using a combination of RT-PCR and mRNA in situ hybridization analyses., Key Results: Corona development starts as a ring of tissue at the base of petals. The outer radii and operculum initiate first at the periphery, followed by the inner radii and pali toward the center, and finally an annulus beneath the operculum. Late in development, a limen, the innermost component of the corona, develops from the side of the androgynophore. RT-PCR analyses indicate that the B-class genes PcPI and PcTM6 and C-class gene PcAG were all expressed in mature coronas. However, mRNA in situ hybridization analyses revealed complex temporal patterns of gene expression in the different corona elements., Conclusions: Our data support the hypothesis that the corona is a composite structure, with the radii, pali, and operculum homologous to stamens, and the limen, which only expresses PcTM6, considered to be a novel structure distinct from the androgynophore.

The aim of this study was to investigate the effects of two common food proteins on human enamel erosion in vitro. Erosion was measured by non-contact profilometry in citric, malic and lactic acids at pH 2.8, 3.2 and 3.8 and five commercially available soft drinks, in the presence of a salivary pellicle. Whole milk casein or hen egg ovalbumin was added to the acid solutions and drinks at 0.2% w/v, and the effect on erosion was determined by comparison with the corresponding solution without protein. Casein significantly reduced erosion in all but two solutions. The effects of the individual subfractions of casein in citric acid at pH 3.2 were similar to that of whole casein. Ovalbumin reduced erosion in some solutions, but the magnitude of the reduction was less than that with casein. A greater proportional reduction in erosion was seen in citric acid than in malic or lactic acids. We postulate that the mechanism involves adsorption of proteins to the pellicle or the enamel surface, forming a protein film with enhanced erosion-inhibiting properties. The citrate ion may play an active stabilising role, since erosion reduction was less in the other acids. In conclusion, casein and, to a lesser extent, ovalbumin show promise as potential anti-erosive additives to drinks., (Copyright © 2010 S. Karger AG, Basel.)

Hydroxyapatite is the main constituent of the dental hard tissues, and in vivo its dissolution in acids leads to the pathological condition of dental erosion. Food proteins which inhibit hydroxyapatite dissolution may find application as erosion-reducing agents in food and drink products. The aim of this study was to investigate the egg protein ovalbumin as a potential inhibitor of hydroxyapatite dissolution in acidic solutions, with conditions representative of dental erosion. The dissolution rate of hydroxyapatite discs was measured in an acidic solution as a function of pH, calcium concentration, ovalbumin concentration and acid type. All experiments were performed in triplicate. 0.2% w/v ovalbumin significantly reduced the dissolution rate in citric acid by 50-75% over the pH range 2.80-4.00, and by 45-60% in solutions with calcium concentrations of up to 20 mM (p < 0.05). The effect was persistent for several rinses after the initial exposure to the protein. 0.02% w/v ovalbumin significantly reduced the dissolution of hydroxyapatite in citric acid by 30-55%. Ovalbumin did not, however, statistically significantly reduce the hydroxyapatite dissolution rate in malic or lactic acids. The effect is ascribed to adsorption and partial, reversible denaturation of ovalbumin on the hydroxyapatite surface. There may be some interaction between ovalbumin and the citrate ion which promotes the adsorption of protein in the presence of citric acid. Ovalbumin shows promise as a potential erosion-reducing additive to citrus-based drinks., (Copyright 2008 S. Karger AG, Basel.)

Objective: To investigate how enamel loss due to erosion, and due to cycling of erosion and abrasion, depends on compositional parameters of soft drinks, and particularly whether the thickness of the erosive softened layer is a function of drink composition., Setting: University dental hospital research laboratory in the UK, 2004., Materials and Methods: Six drinks were chosen based on their popularity and composition: apple juice, orange juice, apple drink, orange drink, cranberry drink and 'ToothKind' blackcurrant drink. Group A samples (n = 36) were exposed to soft drinks at 36 degrees C for six consecutive 10 minute periods. Group B samples (n = 36) were subjected to alternating erosion and toothbrushing, repeated six times. Enamel loss was measured using optical profilometry., Results: Group A: significant enamel loss was seen for all drinks (p < 0.001). Erosion was correlated with pH and calcium concentration but not phosphate concentration or titratable acidity. Group B: significant additional material loss due to toothbrush abrasion occurred with all drinks. Abrasive enamel loss differed between the drinks and was positively correlated with drink erosive potential., Conclusion: Enamel loss by erosion is exacerbated by subsequent abrasion. The amount of softened enamel removed by toothbrushing is a function of the chemical composition of the erosive medium.

Microarrays have become a standard tool for investigating gene function and more complex microarray experiments are increasingly being conducted. For example, an experiment may involve samples from several groups or may investigate changes in gene expression over time for several subjects, leading to large three-way data sets. In response to this increase in data complexity, we propose some extensions to the plaid model, a biclustering method developed for the analysis of gene expression data. This model-based method lends itself to the incorporation of any additional structure such as external grouping or repeated measures. We describe how the extended models may be fitted and illustrate their use on real data.

Malaria is a global problem, and there is a critical need for further understanding of the disease process. When malarial parasites invade and develop within the bloodstream, they stimulate a profound host response whose main clinical sign is fever. To explore this response, we measured host gene expression in whole blood from Kenyan children hospitalized with either acute malaria or other febrile illnesses. Genomewide analysis of expression identified 2 principal gene-expression profiles related to neutrophil and erythroid activity. In addition to these general acute responses, a third gene-expression profile was associated with host parasitemia; mediators of erythrophagocytosis and cellular stress were notable components of this response. The delineation of subjects on the basis of patterns of gene expression provides a molecular perspective of the host response to malaria and further functional insight into the underlying processes of pathogenesis.

Background: Myocardial failure has a central role in the complex pathophysiology of septic shock and contributes to organ failure and death. During the sepsis-induced inflammatory process, specific factors are released that depress myocardial contractile function. We aimed to identify these mediators of myocardial depression in meningococcal septic shock., Methods: We combined gene-expression profiling with protein and cellular methods to identify a serum factor causing cardiac dysfunction in meningococcal septic shock. We identified genes that were significantly upregulated in blood after exposure to meningococci. We then selected for further analysis those genes whose protein products had properties of a myocardial depressant factor--specifically a 12-25 kDa heat-stable protein that is released into serum shortly after onset of meningococcal infection., Findings: We identified 174 significantly upregulated genes in meningococcus-infected blood: six encoded proteins that were of the predicted size and had characteristics of a myocardial depressant factor. Of these, interleukin 6 caused significant myocardial depression in vitro. Removal of interleukin 6 from serum samples of patients with meningococcaemia and from supernatants of inflammatory cells stimulated by meningococci in vitro abolished the negative inotropic activity. Furthermore, concentrations in serum of interleukin 6 strongly predicted degree of myocardial dysfunction and severity of disease in children with meningococcal septic shock., Interpretation: Interleukin 6 is a mediator of myocardial depression in meningococcal disease. This cytokine and its downstream mediators could be a target for future treatment strategies.