Psychocultural Studies: Has the Time Come?

Handbook of Cross-Cultural Psychology. Perspectives. Volume 1 . Harry C. Triandis and Willliam Wilson Lambert , eds.
Handbook of Cross-Cultural Psychology. Methodology. Volume 2 . Harry C. Triandis and John W. Berry eds.
Handbook of Cross-Cultural Psychology. Basic Processes. Volume 1 . Harry C. Triandis and Walter Lonner , eds.
Handbook of Cross-Cultural Psychology. Developmental Psychology. Volume 4 . Harry C. Triandis and Alastair Heron , eds.
Handbook of Cross-Cultural Psychology. Social Psychology. Volume 5 . Harry C. Triandis and Richard W. Brislin eds.
Handbook of Cross-Cultural Psychology. Psychopathology, Volume 6 . Harry C. Triandis and Juris G. Draguns eds.
Cross-cultural Contributions of Psychology . Lutz H. Echkensberger, Walter J. Lonner and Ype H. Poortinga eds.
Perspectives on Cross-Cultural Psychology . Anthony J. Marsella. Roland G. Tharp and Thomas J. Ciborowski. eds.
Studies in Cross-Culturla Psychology. Volume 2 . Neil Warren , ed.     

Has the Time Come for Big Science in Wildlife Health?

The consequences of wildlife emerging diseases are global and profound with increased burden on the public health system, negative impacts on the global economy, declines and extinctions of wildlife species, and subsequent loss of ecological integrity. Examples of health threats to wildlife include Batrachochytrium dendrobatidis, which causes a cutaneous fungal infection of amphibians and is linked to declines of amphibians globally; and the recently discovered Pseudogymnoascus (Geomyces) destructans, the etiologic agent of white nose syndrome which has caused precipitous declines of North American bat species. Of particular concern are the novel pathogens that have emerged as they are particularly devastating and challenging to manage. A big science approach to wildlife health research is needed if we are to make significant and enduring progress in managing these diseases. The advent of new analytical models and bench assays will provide us with the mathematical and molecular tools to identify and anticipate threats to wildlife, and understand the ecology and epidemiology of these diseases. Specifically, new molecular diagnostic techniques have opened up avenues for pathogen discovery, and the application of spatially referenced databases allows for risk assessments that can assist in targeting surveillance. Long-term, systematic collection of data for wildlife health and integration with other datasets is also essential. Multidisciplinary research programs should be expanded to increase our understanding of the drivers of emerging diseases and allow for the development of better disease prevention and management tools, such as vaccines. Finally, we need to create a National Fish and Wildlife Health Network that provides the operational framework (governance, policies, procedures, etc.) by which entities with a stake in wildlife health cooperate and collaborate to achieve optimal outcomes for human, animal, and ecosystem health.     

Point of Care Testing for the Diagnosis of Fungal Infections: Are We There Yet?

Diagnostic tools for invasive fungal infections have continuously improved within the last decades. Nowadays, cultural methods, antigen testing, and molecular tests, such as polymerase chain reaction, are widely used. These methods, however, are accompanied with different limitations as various availability, various turnaround time or high costs. A new generation of point-of-care test has shown promising results in various studies and may overcome some of these limitations. We therefore reviewed the literature for the most promising new point-of-care tests for invasive aspergillosis (Aspergillus-specific lateral-flow device test, Aspergillus proximity ligation antigen assay), cryptococcosis (cryptococcal lateral-flow assay), and for histoplasmosis (loop-mediated isothermal amplification assay).     

Is There Still a Place for Conventional Amphotericin B in the Treatment of Neonatal Fungal Infections?

Neonatal invasive fungal infections (IFIs) remain an increasing problem associated with high rates of morbidity and mortality, as well as late-onset neurodevelopmental implications. Invasive candidiasis remains the leading neonatal IFI. Candida albicans is the fungal species most often affecting this population, although a changing epidemiologic incidence to non-albicans Candida species is reported in some neonatal intensive care units. Many treatment recommendations are extrapolated from adult populations, emphasizing the need to establish the optimal antifungal agent, dosage, and duration of therapy in neonates. Historically, conventional amphotericin B has been considered an efficient and safe treatment approach for most neonatal IFIs. More recently, lipid formulations of amphotericin B have been studied, used alone or in combination with other antifungal agents such as azoles or echinocandins. The aim of this article is to review the published experience in the use of amphotericin B formulations to treat neonatal IFIs.     

Are bloodstream leukocytes Trojan Horses for the metastasis of Staphylococcus aureus?

Staphylococcus aureus bacteraemia remains very difficult to treat, and a large proportion of cases result in potentially lethal metastatic infection. Unpredictable and persistent bacteraemia in the face of highly active, usually bactericidal antibiotics is the strongest predictor of death or disseminated disease. Although S. aureus has conventionally been considered an extracellular pathogen, much evidence demonstrates that it can survive intracellularly. In this Opinion article, we propose that phagocytes, and specifically neutrophils, represent a privileged site for S. aureus in the bloodstream, offering protection from most antibiotics and providing a mechanism by which the bacterium can travel to and infect distant sites. Furthermore, we suggest how this can be experimentally confirmed and how it may prompt a change in the current paradigm of S. aureus bacteraemia and identify better treatment options for improved clinical outcomes.     

Molecular biology of cell nonpermissiveness to retroviruses. Has the time come?

The problem of host cell nonpermissiveness to retrovirus infection is characterized and illustrated on several retroviral models, including the role of viral receptors, cell fusion, and endogenous retroviral genomes as modifiers of the outcome of retroviral infection. Special attention is paid to different barriers against the infection of mammalian cells with avian leukosis/sarcoma viruses (ALV/ASV). Even when avian retroviruses become integrated in mammalian cells, several blocks at the level of provirus expression, processing of viral RNAs, and posttranslational modification prevent virus production in such virogenic cells. The significance of these blocks and new strategies making it possible to overcome some of them are discussed in relation to the development of ALV/ASV-based vectors suitable for gene therapy in mammals.     

Current Status in Diagnosis of Scedosporium Infections: What Is the Impact of New Molecular Methods?

Scedosporium species are increasingly encountered as fungal pathogens. Species identification is important due to species-specific differences in epidemiology, antifungal susceptibility and virulence. Histology and culture-based identification are hampered by their low sensitivity and specificity. The use of new selective media has improved the recovery rate from clinical samples. Molecular methods, including multiplex PCR, PCR-RFLP analysis, DNA sequencing, oligonucleotide arrays, real-time PCR, rolling circle amplification, are increasingly used for species identification. Most recently, Matrix-Assisted Laser Desorption-Time of Flight Mass Spectrometry has been successfully applied as a tool for rapid identification of clinically relevant Scedosporium species. This review aims to summarize the methods currently used to guide the clinical microbiology laboratory in the selection of the most appropriate identification techniques. This will aid the laboratory in making a fast and reliable diagnosis that enables the clinician to make correct treatment choices.     

Time Series Analysis of Particle Tracking Data for Molecular Motion on the Cell Membrane

Biophysicists use single particle tracking (SPT) methods to probe the dynamic behavior of individual proteins and lipids in cell membranes. The mean squared displacement (MSD) has proven to be a powerful tool for analyzing the data and drawing conclusions about membrane organization, including features like lipid rafts, protein islands, and confinement zones defined by cytoskeletal barriers. Here, we implement time series analysis as a new analytic tool to analyze further the motion of membrane proteins. The experimental data track the motion of 40 nm gold particles bound to Class I major histocompatibility complex (MHCI) molecules on the membranes of mouse hepatoma cells. Our first novel result is that the tracks are significantly autocorrelated. Because of this, we developed linear autoregressive models to elucidate the autocorrelations. Estimates of the signal to noise ratio for the models show that the autocorrelated part of the motion is significant. Next, we fit the probability distributions of jump sizes with four different models. The first model is a general Weibull distribution that shows that the motion is characterized by an excess of short jumps as compared to a normal random walk. We also fit the data with a chi distribution which provides a natural estimate of the dimension d of the space in which a random walk is occurring. For the biological data, the estimates satisfy 1<d<2, implying that particle motion is not confined to a line, but also does not occur freely in the plane. The dimension gives a quantitative estimate of the amount of nanometer scale obstruction met by a diffusing molecule. We introduce a new distribution and use the generalized extreme value distribution to show that the biological data also have an excess of long jumps as compared to normal diffusion. These fits provide novel estimates of the microscopic diffusion constant.     

Beyond Transcription—New Mechanisms for the Regulation of Molecular Chaperones

Molecular chaperones are an essential part of the universal heat shock response that allows organisms to survive stress conditions that cause intracellular protein unfolding. During the past few years, two new mechanisms have been found to control the activity of several chaperones under stress conditions—the regulation of chaperone activity by the redox state and by the temperature of the environment. Hsp33, for example, is redox-regulated. Hsp33 is specifically activated by disulfide bond formation during oxidative stress, where it becomes a highly efficient chaperone holdase that binds tightly to unfolding proteins. Certain small heat shock proteins, such as Hsp26 and Hsp16.9, on the other hand, are temperature regulated. Exposure to heat shock temperatures causes these oligomeric proteins to disassemble, thereby changing them into highly efficient chaperones. The ATP-dependent chaperone folding system DnaK/DnaJ/GrpE also appears to be temperature regulated, switching from a folding to a holding mode during heat stress. Both of these novel post-translational regulatory strategies appear to have one ultimate goal: to significantly increase the substrate binding affinity of the affected chaperones under exactly those stress conditions that require their highest chaperone activity. This ensures that protein folding intermediates remain bound to the chaperones under stress conditions and are released only after the cells return to non-stress conditions.     

Molecular Mechanism That Induces Activation of Sp?tzle,the Ligand for the Drosophila Toll Receptor

The Drosophila Toll receptor is activated by an endogenous cytokine ligand Spätzle. Active ligand is generated in response to positional cues in embryonic dorso-ventral patterning and microbial pathogens in the insect immune response. Spätzle is secreted as a pro-protein and is processed into an active form by the serine endoproteases Easter and Spätzle-processing enzyme during dorso-ventral patterning and infection, respectively. Here, we provide evidence for the molecular mechanism of this activation process. We show that the Spätzle prodomain masks a predominantly hydrophobic region of Spätzle and that proteolysis causes a conformational change that exposes determinants that are critical for binding to the Toll receptor. We also gather that a conserved sequence motif in the prodomain presents features of an amphipathic helix likely to bind a hydrophobic cleft in Spätzle thereby occluding the putative Toll binding region. This mechanism of activation has a striking similarity to that of coagulogen, a clotting factor of the horseshoe crab, an invertebrate that has changed little in 400 million years. Taken together, our findings demonstrate that an ancient passive defense system has been adapted during evolution and converted for use in a critical pathway of innate immune signaling and embryonic morphogenesis.     

Animal Cognition: An Insect's Sense of Time?

For Immanuel Kant, time was the very form of the inner sense, the bedrock of our consciousness and also the origin of arithmetic ability. New research on bumblebees has shown that even an invertebrate with a brain the size of a pinhead can actively sense the passage of elapsed time, allowing it to predict when certain salient events will occur in the future.     

Does the Committee Peer Review Select the Best Applicants for Funding? An Investigation of the Selection Process for Two European Molecular Biology Organization Programmes

Does peer review fulfill its declared objective of identifying the best science and the best scientists? In order to answer this question we analyzed the Long-Term Fellowship and the Young Investigator programmes of the European Molecular Biology Organization. Both programmes aim to identify and support the best post doctoral fellows and young group leaders in the life sciences. We checked the association between the selection decisions and the scientific performance of the applicants. Our study involved publication and citation data for 668 applicants to the Long-Term Fellowship programme from the year 1998 (130 approved, 538 rejected) and 297 applicants to the Young Investigator programme (39 approved and 258 rejected applicants) from the years 2001 and 2002. If quantity and impact of research publications are used as a criterion for scientific achievement, the results of (zero-truncated) negative binomial models show that the peer review process indeed selects scientists who perform on a higher level than the rejected ones subsequent to application. We determined the extent of errors due to over-estimation (type I errors) and under-estimation (type 2 errors) of future scientific performance. Our statistical analyses point out that between 26% and 48% of the decisions made to award or reject an application show one of both error types. Even though for a part of the applicants, the selection committee did not correctly estimate the applicant''s future performance, the results show a statistically significant association between selection decisions and the applicants'' scientific achievements, if quantity and impact of research publications are used as a criterion for scientific achievement.     

Improved Radiographic Imaging of Invasive Fungal Disease: The Cornerstone to Antifungal Stewardship in the Hematology Units?

Empirical or fever-driven antifungal treatment strategies are widely recognized to result in overtreatment of patients and excessive cost. As a result, diagnostic-driven approaches for managing invasive fungal diseases (IFDs) in hematology units have been proposed that rely on early non-specific radiologic findings frequent testing with non-culture-based biomarkers (e.g., galactomannan, PCR) as a trigger for antifungal treatment. However, the performance of these non-culture-based biomarker tests varies significantly from one center to the next, and their sensitivity is reduced by prior antifungal therapy. Moreover, many clinicians do not have sufficient confidence in their negative predictive value to withhold antifungal treatment. An alternative strategy is to use existing (computer tomography pulmonary angiography) and developing technologies (immune-positron emission tomography with specific antibodies) to improve the sensitivity and specificity radiological for IFD. Currently available data suggest that these newer techniques may have similar or better diagnostic performance as biomarker tests with high negative predictive values. In this monograph, we review challenges and recent progress in radiological imaging of IFD in hematology patients, and discuss its potential implications for antifungal stewardship.     

Has the code for protein translocation been broken?

Polypeptides chains are segregated by the translocon channel into secreted or membrane-inserted proteins. Recent reports claim that an in vivo system has been used to break the "amino acid code" used by translocons to make the determination of protein type (i.e. secreted or membrane-inserted). However, the experimental setup used in these studies could have confused the derivation of this code, in particular for polar amino acids. These residues are likely to undergo stabilizing interactions with other protein components in the experiment, shielding them from direct contact with the inhospitable membrane. Hence, it is our view that the "code" for protein translocation has not yet been deciphered and that further experiments are required for teasing apart the various energetic factors contributing to protein translocation.