Differential 24‐Hour Variation of Alertness and Subjective Tension in Process Controllers: Investigation of the Relationship with Body Temperature and Heart Rate

The effects of shift and time‐on‐shift on alertness and perceived tension, as well as related physiological variables, were investigated in satellite controllers working a rapid forward rotating three‐shift system. In controlled laboratory conditions, subjective tension and HR have been reported to display circadian variation and marked sensitivity to external factors. We examined whether circadian variations were masked for these particular variables in real‐job conditions, unlike for alertness and body temperature, which have been repeatedly shown to display circadian variation in these conditions. This hypothesis was tested in a repeated‐measures design by collecting alertness and tension self‐reports and recording operators' sublingual temperature on three occasions on each shift and HR continuously throughout shifts. Alertness and body temperature varied according to a typical diurnal trend; subjective tension was only enhanced on the initial recording of each shift (compared to the remaining ones), while HR displayed an intermediary trend. Intra‐subject correlations revealed a positive relationship between alertness, oral temperature, and HR, while no such relationship was found for subjective tension. These results support the hypothesis of a close dependence of alertness and temperature, and to a lesser extent for HR, on endogenous mechanisms in this job‐situation. In addition, some situation‐specific factors, such as job‐demand, would affect subjective tension and partially mask the circadian variations in HR.     

Targeting the human parasite Leishmania donovani: Discovery of a new promising anti-infectious pharmacophore in 3-nitroimidazo[1,2-a]pyridine series

We report herein the discovery of antileishmanial molecules based on the imidazo[1,2-a]pyridine ring. In vitro screenings of imidazopyridines belonging to our chemical library, toward the promastigotes stage of Leishmania donovani, J774A.1 murine and HepG2 human cells, permitted to identify three selective hit-compounds (12, 20 and 28). New derivatives were then synthesized to allow structure–activity and –toxicity relationships analyses, enabling to characterize a lead-compound (44) displaying both a high potency (IC₅₀ = 1.8 μM) and a good selectivity index, in comparison with three antileishmanial reference drug-compounds (amphotericin B, miltefosine and pentamidine). Moreover, lead-compound 44 also exhibits good in vitro activity against the intracellular amastigote stage of L. donovani. Thus, the 6-halo-3-nitro-2-(phenylsulfonylmethyl)imidazo[1,2-a]pyridine scaffold appears as a new promising selective antileishmanial pharmacophore, especially when substituted at position 8 by a bromine atom.     

Fish ladders select fish traits on migration–still a growing problem for natural fish populations

We investigated the potential selective effect of fish ladders on physiological and morphological profiles of the curimbatá, Prochilodus lineatus, during reproductive migration in Brazil. We registered sex, body weight and length, plasma glucose, hepatosomatic and gonadosomatic indices (HSI and GSI, respectively), hematocrit, leucocrit, blood cell and nucleus areas, and the diameter of white and red muscle fibers in fish sampled at the bottom (downstream) and at the top (upstream) of a fish ladder at a hydroelectric dam. Males and females at the top of the ladder showed higher size (weight and length), white muscle fiber diameters, plasma glucose levels and lower hematocrit when compared with those at the bottom. These size and muscle traits assist fish to overcome the ladder barrier and bypass the dam, an effort that might be reflected in the glucose levels. Females also showed higher GSI at the top of the fish ladder, a trait possibly facilitating their reproduction upstream. These results indicate that a dam system favors fish with specific morphological–physiological profile. This may have a strong influence upon upstream fish populations over generations and implies the presence of artificial selective pressure.     

NK cells enhance dendritic cell response against parasite antigens via NKG2D pathway

Recent studies have shown that NK-dendritic cell (DC) interaction plays an important role in the induction of immune response against tumors and certain viruses. Although the effect of this interaction is bidirectional, the mechanism or molecules involved in this cross-talk have not been identified. In this study, we report that coculture with NK cells causes several fold increase in IL-12 production by Toxoplasma gondii lysate Ag-pulsed DC. This interaction also leads to stronger priming of Ag-specific CD8+ T cell response by these cells. In vitro blockade of NKG2D, a molecule present on human and murine NK cells, neutralizes the NK cell-induced up-regulation of DC response. Moreover, treatment of infected animals with Ab to NKG2D receptor compromises the development of Ag-specific CD8+ T cell immunity and reduces their ability to clear parasites. These studies emphasize the critical role played by NKG2D in the NK-DC interaction, which apparently is important for the generation of robust CD8+ T cell immunity against intracellular pathogens. To the best of our knowledge, this is the first work that describes in vivo importance of NKG2D during natural infection.     

Learn from the Best

What is more inspiring than a discussion with the leading scientists in your field? As a student or a young researcher, you have likely been influenced by mentors guiding you in your career and leading you to your current position. Any discussion with or advice from an expert is certainly very helpful for young people. But how often do we have the opportunity to meet experts? Do we make the most out of these situations? Meetings organized for young scientists are a great opportunity not only for the attendees: they are an opportunity for experts to meet bright students and learn from them in return. In this article, we introduce several successful events organized by Regional Student Groups all around the world, bridging the gap between experts and young scientists. We highlight how rewarding it is for all participants: young researchers, experts, and organizers. We then discuss the various benefits and emphasize the importance of organizing and attending such meetings. As a young researcher, seeking mentorship and additional skills training is a crucial step in career development. Keep in mind that one day, you may be an inspiring mentor, too.     

Crossing Borders for Science

Exchanging ideas with like-minded, enthusiastic people interested in the same topic is crucial for the advancement of a scientist''s career. Several Regional Student Groups (RSGs) of the International Society for Computational Biology (ISCB) Student Council have cooperated in the last six years to organize scientific workshops and conferences. With motivated students, it is possible to create a memorable event for fellow scientists; in doing so, the organizers gain valuable experiences. While collaborating across borders and time zones can be difficult, feedback from event organizers was always positive. When limited resources are juxtaposed with great ideas and a network of contacts, the outcome is always an amazing experience, despite organizers being separated geographically across different countries.     

The miR‐379/miR‐410 cluster at the imprinted Dlk1‐Dio3 domain controls neonatal metabolic adaptation

In mammals, birth entails complex metabolic adjustments essential for neonatal survival. Using a mouse knockout model, we identify crucial biological roles for the miR‐379/miR‐410 cluster within the imprinted Dlk1‐Dio3 region during this metabolic transition. The miR‐379/miR‐410 locus, also named C14MC in humans, is the largest known placental mammal‐specific miRNA cluster, whose 39 miRNA genes are expressed only from the maternal allele. We found that heterozygote pups with a maternal—but not paternal—deletion of the miRNA cluster display partially penetrant neonatal lethality with defects in the maintenance of energy homeostasis. This maladaptive metabolic response is caused, at least in part, by profound changes in the activation of the neonatal hepatic gene expression program, pointing to as yet unidentified regulatory pathways that govern this crucial metabolic transition in the newborn's liver. Not only does our study highlight the physiological importance of miRNA genes that recently evolved in placental mammal lineages but it also unveils additional layers of RNA‐mediated gene regulation at the Dlk1‐Dio3 domain that impose parent‐of‐origin effects on metabolic control at birth and have likely contributed to mammal evolution.     

Cryptosporidium parvum-induced ileo-caecal adenocarcinoma and Wnt signaling in a mouse model

Cryptosporidium species are apicomplexan protozoans that are found worldwide. These parasites constitute a large risk to human and animal health. They cause self-limited diarrhea in immunocompetent hosts and a life-threatening disease in immunocompromised hosts. Interestingly, Cryptosporidium parvum has been related to digestive carcinogenesis in humans. Consistent with a potential tumorigenic role of this parasite, in an original reproducible animal model of chronic cryptosporidiosis based on dexamethasone-treated or untreated adult SCID mice, we formerly reported that C. parvum (strains of animal and human origin) is able to induce digestive adenocarcinoma even in infections induced with very low inoculum. The aim of this study was to further characterize this animal model and to explore metabolic pathways potentially involved in the development of C. parvum-induced ileo-caecal oncogenesis. We searched for alterations in genes or proteins commonly involved in cell cycle, differentiation or cell migration, such as β-catenin, Apc, E-cadherin, Kras and p53. After infection of animals with C. parvum we demonstrated immunohistochemical abnormal localization of Wnt signaling pathway components and p53. Mutations in the selected loci of studied genes were not found after high-throughput sequencing. Furthermore, alterations in the ultrastructure of adherens junctions of the ileo-caecal neoplastic epithelia of C. parvum-infected mice were recorded using transmission electron microscopy. In conclusion, we found for the first time that the Wnt signaling pathway, and particularly the cytoskeleton network, seems to be pivotal for the development of the C. parvum-induced neoplastic process and cell migration of transformed cells. Furthermore, this model is a valuable tool in understanding the host-pathogen interactions associated with the intricate infection process of this parasite, which is able to modulate host cytoskeleton activities and several host-cell biological processes and remains a significant cause of infection worldwide.KEY WORDS: SCID mouse model, Cryptosporidiosis, Wnt pathway, Cytoskeleton, Digestive cancer     

Adaptation of the Wine Bacterium Oenococcus oeni to Ethanol Stress: Role of the Small Heat Shock Protein Lo18 in Membrane Integrity

Malolactic fermentation in wine is often carried out by Oenococcus oeni. Wine is a stressful environment for bacteria because ethanol is a toxic compound that impairs the integrity of bacterial membranes. The small heat shock protein (sHsp) Lo18 is an essential actor of the stress response in O. oeni. Lo18 prevents the thermal aggregation of proteins and plays a crucial role in membrane quality control. Here, we investigated the interaction between Lo18 and four types of liposomes: one was prepared from O. oeni grown under optimal growth conditions (here, control liposomes), one was prepared from O. oeni grown in the presence of 8% ethanol (here, ethanol liposomes), one was prepared from synthetic phospholipids, and one was prepared from phospholipids from Bacillus subtilis or Lactococcus lactis. We observed the strongest interaction between Lo18 and control liposomes. The lipid binding activity of Lo18 required the dissociation of oligomeric structures into dimers. Protein protection experiments carried out in the presence of the liposomes from O. oeni suggested that Lo18 had a higher affinity for control liposomes than for a model protein. In anisotropy experiments, we mimicked ethanol action by temperature-dependent fluidization of the liposomes. Results suggest that the principal determinant of Lo18-membrane interaction is lipid bilayer phase behavior rather than phospholipid composition. We suggest a model to describe the ethanol adaptation of O. oeni. This model highlights the dual role of Lo18 in the protection of proteins from aggregation and membrane stabilization and suggests how modifications of phospholipid content may be a key factor determining the balance between these two functions.