Apoptosis in Activated T Cells – What Are the Triggers,and What the Signal Transducers?

At the end of an immune response, apoptosis drastically reduces the numbers of activated T cells. It has been a matter of intense research how this form of apoptosis is regulated and initiated, and a number of proteins have been identified that contribute to this process. The present, widely accepted model assumes that the interplay of pro- and anti-apoptotic Bcl-2 family members determines the onset of activated T cell death, with the BH3-only protein Bim activating pro-apoptotic Bax/Bak. In the search for up-stream signals, factors from other immune cells have been shown to play a role, and the NF-κB family member Bcl-3 has been implicated as a signalling-intermediate in T cells. Recent work has tested the interrelation of these factors and has suggested that Bcl-3 acts as a regulator of Bim activation, that the induction of apoptosis through Bim can be complemented by its relative Puma, and that the presence of certain cytokines during T cell activation delays the activation of Bim and Puma. Here we discuss these recent insights and provide a view on how the regulation of activated T cell death is achieved and how extrinsic signals may translate into the activation of the apoptotic pathway.     

Temporal Patterns of Influenza A and B in Tropical and Temperate Countries: What Are the Lessons for Influenza Vaccination?

IntroductionDetermining the optimal time to vaccinate is important for influenza vaccination programmes. Here, we assessed the temporal characteristics of influenza epidemics in the Northern and Southern hemispheres and in the tropics, and discuss their implications for vaccination programmes.MethodsThis was a retrospective analysis of surveillance data between 2000 and 2014 from the Global Influenza B Study database. The seasonal peak of influenza was defined as the week with the most reported cases (overall, A, and B) in the season. The duration of seasonal activity was assessed using the maximum proportion of influenza cases during three consecutive months and the minimum number of months with ≥80% of cases in the season. We also assessed whether co-circulation of A and B virus types affected the duration of influenza epidemics.Results212 influenza seasons and 571,907 cases were included from 30 countries. In tropical countries, the seasonal influenza activity lasted longer and the peaks of influenza A and B coincided less frequently than in temperate countries. Temporal characteristics of influenza epidemics were heterogeneous in the tropics, with distinct seasonal epidemics observed only in some countries. Seasons with co-circulation of influenza A and B were longer than influenza A seasons, especially in the tropics.DiscussionOur findings show that influenza seasonality is less well defined in the tropics than in temperate regions. This has important implications for vaccination programmes in these countries. High-quality influenza surveillance systems are needed in the tropics to enable decisions about when to vaccinate.     

The Tetanus Neurotoxin‐Sensitive and Insensitive Routes to and from the Plasma Membrane: Fast and Slow Pathways?

Intracellular membrane trafficking in eukaryotes involves the budding of vesicles from a donor compartment, their translocation, and subsequent fusion with a target membrane. This last step has been shown to involve SNARE proteins, classified into two categories, vesicular (v)-SNAREs and target (t)-SNAREs. It is the pairing of v- and t-SNAREs that is responsible for bringing the lipid bilayers together for membrane fusion. Key to the discovery of SNAREs is the sensitivity of their neuronal synaptic prototypes, which mediate the release of neurotransmitters, to clostridial neurotoxins. In this review, we focus on tetanus neurotoxin-sensitive and tetanus neurotoxin-insensitive v-SNAREs, in particular synaptobrevin and cellubrevin, both tetanus neurotoxin-sensitive and Tetanus neurotoxin-Insensitive Vesicle-Associated Membrane Protein (TI-VAMP, also called VAMP7). The brevins are characterized by an RD sequence in the middle of their SNARE motif whereas TI-VAMP has an RG sequence. These two categories of exocytic v-SNAREs define two important routes to and from the plasma membrane: one sensitive, the other insensitive to tetanus neurotoxin. We also discuss the central role of the endosomal system that could be considered, as already suggested for Rab proteins, as a mosaic of v-SNAREs, thus raising the question of whether or not these two routes can merge, and if so, how and where.     

What Would Jaws Do? The Tyranny of Film and the Relationship between Gaze and Higher-Level Narrative Film Comprehension

What is the relationship between film viewers’ eye movements and their film comprehension? Typical Hollywood movies induce strong attentional synchrony—most viewers look at the same things at the same time. Thus, we asked whether film viewers’ eye movements would differ based on their understanding—the mental model hypothesis—or whether any such differences would be overwhelmed by viewers’ attentional synchrony—the tyranny of film hypothesis. To investigate this question, we manipulated the presence/absence of prior film context and measured resulting differences in film comprehension and eye movements. Viewers watched a 12-second James Bond movie clip, ending just as a critical predictive inference should be drawn that Bond’s nemesis, “Jaws,” would fall from the sky onto a circus tent. The No-context condition saw only the 12-second clip, but the Context condition also saw the preceding 2.5 minutes of the movie before seeing the critical 12-second portion. Importantly, the Context condition viewers were more likely to draw the critical inference and were more likely to perceive coherence across the entire 6 shot sequence (as shown by event segmentation), indicating greater comprehension. Viewers’ eye movements showed strong attentional synchrony in both conditions as compared to a chance level baseline, but smaller differences between conditions. Specifically, the Context condition viewers showed slightly, but significantly, greater attentional synchrony and lower cognitive load (as shown by fixation probability) during the critical first circus tent shot. Thus, overall, the results were more consistent with the tyranny of film hypothesis than the mental model hypothesis. These results suggest the need for a theory that encompasses processes from the perception to the comprehension of film.     

Causal Relationship between Physiological and Pathological Processes in the Brain and in the Gastrointestinal Tract: The Brain–Intestine Axis

Biophysics - The brain and gastrointestinal tract are the most important organs responsible for detecting, transmitting, integrating, and responding to signals coming from the internal and external...     

Red Fluorescing Phototrophic Picoplankton in the Laurentian Great Lakes: What Are They and What Are They Doing?

Epifluorescence microscopy, flow cytometry, and transmission electron microscopy were used to characterize the community of red fluorescing (emission >665 nm when excited with blue light) phototrophic picoplankton (RFPP) in lakes Huron and Michigan. A population of coccoid to ovate eukaryotic cells with a mean size of 1.2 μm dominated the RFPP community in both surface and deep water samples. Abundant prochlorophyte populations were not found in any samples. Comparisons of counts with epifluorescence microscopy and flow cytometry, revealed that RFPP were adequately enumerated with standard epifluorescence microscopy. These RFPP were significant contributors to total phototrophic picoplankton abundance in both lakes Michigan (24%) and Huron (18%), with maximum seasonal abundance during the May-June period (surface mixing layer temperatures, 3-9 °C). During thermal stratification, maximum vertical abundance was found in the metalimnion/hypolimnion at the 1-5% isolumes. RFPP were only minor contributors (1-7%) to total primary production. Growth rates of RFPP measured with dilution and small inocula growth experiments ranged from 0.05-1.0 d⁻¹. Microzooplankton grazing rates on RFPP measured with dilution experiments were similar to estimated growth rates, accounting for 52-280% of growth on any given date.     

Saharan Dust Impacts on Air Quality: What Are the Potential Health Risks in West Africa?

Despite the proximity of the Sahara, very few studies about dust impact on air quality and human health have been conducted in West Africa. The lack of data is a major constraint on our understanding of the impacts on human health in this area. We analyzed PM₁₀ concentrations and horizontal visibility recorded in four West African stations. The pollution levels often exceed the standards defined by many countries/regulatory authorities and have been associated with serious health risks outside Africa. Over the Sahelian stations, 45.6% of the days between November 2006 and March 2007 were likely to impact human health and the studied Sudanian population was exposed to potential health effects every 5 days.     

What is love? The complex relation between values and practice in Vanuatu

The past decade has seen a renewed anthropological interest in values, morality, and ethics. This article engages with this field by demonstrating how values can be strategies as well as ideals, prone to destabilize social order and divide people precisely because they are thought to be shared. The concept of ‘love’, referring to everyday practices of concern and care for others, is a core value for living on Ahamb Island in Vanuatu. However, adherence to the same core value does not necessarily create an ordered social world. Analysing three ethnographic cases, one of them a dispute with fatal consequences, I propose a model for studying values that accommodates ambiguity by uniting the notion of shared social values with individual experience and strategy. A methodological argument is that it is crucial for anthropological studies of values to assess the context for people's shifting interpretations and articulations of value in practice.     

Membrane TNFα: Importance for the Effector Function of Dendritic Cells and Potential Ways of Its Targeted Modulation

Membrane TNFα (mTNFα) is expressed on many immune cell types and performs various biological functions. Dendritic cells (DC) of high-grade glioma patients exhibit impaired cytotoxic activity against TNFα-sensitive HEp-2 tumor cells. The mechanisms leading to the impairment of the TNFα- dependent tumoricidal activity of DC and the possibility of regulating the cytotoxic activity of DC mediated by the TNFα/TNF-R1 signaling pathway have been studied. The study was conducted on healthy donors and patients with newly diagnosed high-grade glioma. DC were generated by culturing the plastic-adherent peripheral blood mononuclear cell fraction in the presence of GM-CSF and interferon-α (IFN-DC). It was shown that the impairment of the cytotoxic activity of patient IFN-DC was associated with a low number of DC expressing mTNFα and a low level of TNFα mRNA expression in DC. IFN-DC of patients exhibited a tendency of high activity of the TNFα-converting enzyme (TACE), which accomplishes shedding of mTNFα from the cell membrane. An increased number of IFN-DC with mTNFα caused by TACE blocking enhanced cytotoxic activity of the patient’s IFN-DC against HEp-2 cells. It was established that exogenous interleukin-2 and extracellular DNA are up-regulators of the mTNFα expression on IFN-DC of the patients, but their effects are mediated by different mechanisms.     

What Are the Roles and Responsibilities of the Media in Disseminating Health Information?

BACKGROUND TO THE DEBATE: In December 2004 three news stories in the popular press suggested that the side effects of single-dose nevirapine, which has been proven to prevent mother-to-child transmission of HIV, had been covered up. Many HIV experts believed that the stories were unwarranted and that they would undermine use of the drug, leading to a rise in neonatal HIV infection. The controversy surrounding these stories prompted the PLoS Medicine editors to ask health journalists, and others with an interest in media reporting of health, to share their views on the roles and responsibilities of the media in disseminating health information.     

Diagnosis and Treatment of Lymphocutaneous Sporotrichosis: What Are the Options?

Lymphocutaneous sporotrichosis is the most common clinical form of cutaneous sporotrichosis. Caused by a complex of dimorphic fungi called Sporothrix schenckii complex, it is an occupational disease, present especially in tropical and subtropical areas, and has been reported in all continents. Diagnosis is established by isolation of the causative agent. Therapy of choice for lymphocutaneous sporotrichosis is itraconazole, and in developing countries, potassium iodide solution. In general, the lymphocutaneous form is considered a mild benign form of the disease, and the majority of cases respond well to treatment in about 3–4 months of therapy. In this paper, we have made a general review of the disease, especially of the epidemiology, clinical features and diagnosis of the lymphocutaneous form, as well as a brief analysis of the advantages and disadvantages of diverse treatments.     

Discordant Phylogeographic Patterns between the Y Chromosome and Mitochondrial DNA in the House Mouse: Selection on the Y Chromosome?

We have compared patterns of geographic variation and molecular divergence of mitochondrial DNA (mtDNA) and Y chromosome over the range of the different subspecies of Mus musculus. MtDNA was typed for 305 nucleotides in the control region, the Y chromosome for 834 base pairs (bp) in Zfy introns and 242 bp in Sry, a Zfy2 18-bp deletion, and two microsatellites. Apparent discrepancies exist between the distributions of the lineages of mtDNA and of the two major Y-chromosome lineages thus defined: some subspecies share the same mtDNA lineage but have different Y-chromosome lineages or vice versa. One microsatellite reveals a geographically clustered variation inside the distribution of each Y-chromosome lineage, showing that new Y-chromosome variants can rapidly spread locally. The two major Y-chromosome lineages have a divergence time only about one fourth of that between mtDNA lineages. Although this recent coalescence of the Y chromosomes between subspecies could partly be due to a lower ancestral polymorphism of the Y chromosome, it suggests that secondary introgression after the radiation of the subspecies might have occurred. There is evidence that the differentiation of the Y-chromosome lineages contributes to partial reproductive isolation between subspecies, and patterns of molecular evolution suggest that selection has played a role in the rapid spread across subspecies.     

Are the birds dangerous for insect pollinators? The relationship between hymenopterans and the red-backed shrike

Studies of the relationships between insectivorous birds and insects have focused on woodland habitats, where insects have usually been regarded as tree pests. But some insects are of the utmost importance to the human economy, especially hymenopterans, which pollinate plants such as fruit trees in orchards. Here we report on a 5-year study of the influence of the red-backed shrike Lanius collurio, a territorial insectivorous bird, on the numbers of hymenopterans in the extensively farmed landscape of eastern Poland. The relevant relationships were based on an analysis of the shrike’s diet and the numbers of hymenopterans in and beyond nesting locations. There was a weak but statistically significant relationship between the proportion of hymenopterans in the red-backed shrike’s diet and the place and time of prey capture, but this was dependent solely on the location of the shrike’s territory. No relationship was found between the numbers of hymenopterans and the presence of the red-backed shrike, agricultural site type or season effect. In conclusion, territorial bird species that occur in low densities probably have only a marginal influence on hymenopterans, including pollinators.     

The “χ” of the Matter: Testing the Relationship between Paleoenvironments and Three Theropod Clades

The view of spinosaurs as dinosaurs of semi-aquatic habits and strongly associated with marginal and coastal habitats are deeply rooted in both scientific and popular knowledge, but it was never statistically tested. Inspired by a previous analysis of other dinosaur clades and major paleoenvironmental categories, here we present our own statistical evaluation of the association between coastal and terrestrial paleoenvironments and spinosaurids, along with other two theropod taxa: abelisaurids and carcharodontosaurids. We also included a taphonomic perspective and classified the occurrences in categories related to potential biases in order to better address our interpretations. Our main results can be summarized as follows: 1) the taxon with the largest amount of statistical evidence showing it positively associated to coastal paleoenvironments is Spinosauridae; 2) abelisaurids and carcharodontosaurids had more statistical evidence showing them positively associated with terrestrial paleoenvironments; 3) it is likely that spinosaurids also occupied spatially inland areas in a way somehow comparable at least to carcharodontosaurids; 4) abelisaurids may have been more common than the other two taxa in inland habitats.