How can immunology contribute to the control of tuberculosis?

Tuberculosis poses a significant threat to mankind. Multidrug-resistant strains are on the rise, and Mycobacterium tuberculosis infection is often associated with human immunodeficiency virus infection. Satisfactory control of tuberculosis can only be achieved using a highly efficacious vaccine. Tuberculosis is particularly challenging for the immune system. The intracellular location of the pathogen shields it from antibodies, and a variety of T-cell subpopulations must be activated to challenge the bacterium's resistance to antibacterial defence mechanisms. A clear understanding of the immune responses that control the pathogen will be important for achieving optimal immunity, and information provided by functional genome analysis of M. tuberculosis will be vital in the design of a future vaccine.     

How do glutamatergic and GABAergic cells contribute to synchronization in the medial septum?

The medial septum-diagonal band (MSDB) complex is considered as a pacemaker for the hippocampal theta rhythm. Identification of the different cell types, their electro-physiological properties and their possible function in the generation of a synchronized activity in the MSDB is a hot topic. A recent electro-physiological study showed the presence of two antiphasically firing populations of parvalbumin containing GABAergic neurons in the MSDB. Other papers described a network of cluster-firing glutamatergic neurons, which is able to generate synchronized activity in the MSDB. We propose two different computer models for the generation of synchronized population theta oscillation in the MSDB and compare their properties. In the first model GABAergic neurons are intrinsically theta periodic cluster-firing cells; while in the second model GABAergic cells are fast-firing cells and receive periodic input from local glutamatergic neurons simulated as cluster-firing cells. Using computer simulations we show that the GABAergic neurons in both models are capable of generating antiphasic theta periodic population oscillation relying on local, septal mechanisms. In the first model antiphasic theta synchrony could emerge if GABAergic neurons form two populations preferentially innervate each other. In the second model in-phase synchronization of glutamatergic neurons does not require specific network structure, and the network of these cells are able to act as a theta pacemaker for the local fast-firing GABAergic circuit. Our simulations also suggest that neurons being non-cluster-firing in vitro might exhibit clustering properties when connected into a network in vivo. Action Editor: David Golomb     

After the crash: How do predators adjust following the invasion of a novel toxic prey type?

The ability of a native predator to adjust to a dangerously toxic invasive species is key to avoiding an ongoing suppression of the predator's population and the trophic cascade of effects that can result. Many species of anurophagous predators have suffered population declines due to the cane toad's (Rhinella marina: Bufonidae) invasion of Australia; these predators can be fatally poisoned from attempting to consume the toxic toad. We studied one such toad‐vulnerable predator, the yellow‐spotted monitor (Varanus panoptes: Varanidae), testing whether changes to the predator's feeding behaviour could explain how the species persists following toad invasion. Wild, free‐roaming lizards from (1) toad‐naïve and (2) toad‐exposed populations were offered non‐toxic native frogs and slightly toxic cane toads (with parotoid glands removed) in standardized feeding trials. Toad‐naïve lizards readily consumed both frogs and toads, with some lizards displaying overt signs of illness after consuming toads. In contrast, lizards from toad‐exposed populations consumed frogs but avoided toads. Repeated encounters with toads did not modify feeding responses by lizards from the toad‐naïve populations, suggesting that aversion learning is limited (but may nonetheless occur). Our results suggest that this vulnerable predator can adjust to toad invasion by developing an aversion to feeding on the toxic invader, but it remains unclear as to whether the lizard's toad‐aversion arises via adaptation or learning.     

How do natural and sexual selection contribute to sympatric speciation?

I use explicit genetic models to investigate the importance of natural and sexual selection during sympatric speciation and to sort out how genetic architecture influences these processes. Assortative mating alone can lead to speciation, but rare phenotypes' disadvantage in finding mates and intermediate phenotypes' advantage due to stabilizing selection strongly impede speciation. Any increase in the number of loci also decreases the likelihood of speciation. Sympatric speciation is then harder to achieve than previously demonstrated by many theoretical studies which assume no mating disadvantage for rare phenotypes and consider a small number of loci. However, when a high level of assortative mating evolves, sexual selection might allow populations to split into dimorphic distributions with peaks corresponding to nearly extreme phenotypes. Competition then works against speciation by favouring intermediate phenotypes and preventing further divergence. The interplay between natural and sexual selection during speciation is then more complex than previously explained.     

Do zwitterions contribute to the ionic strength of a solution?

Capillary electrophoresis has been used to determine whether zwitterions contribute to the ionic strength of a solution, by measuring the mobility of a double-stranded DNA oligomer in cacodylate-buffered solutions containing various concentrations of the ionic salt tetraethylammonium chloride (TEA(+)Cl(-)) or the zwitterion tricine(+/-). The mobility of the DNA decreased as the square root of ionic strength, as expected from the Debye-Hückel-Onsager theory of electrophoresis, when TEA(+)Cl(-) was added to the buffer. However, the mobility was independent of the concentration of added tricine(+/-). Hence, zwitterions do not contribute to the ionic strength of a solution.     

How do transportation-based environmental taxation and globalization contribute to ecological sustainability?

Environmental taxation strategies are recognized as powerful instruments for enhancing environmental quality through emissions reduction globally; however, the ecological effects of green taxes in the transportation sector (ETT) have been largely overlooked. To fill this literature void, we undertake a novel attempt to evaluate the effectiveness of ETT and globalization in attaining ecological sustainability in the presence of energy intensity and real GDP per capita. We employ second-generation Westerlund cointegration, pooled mean group autoregressive distributed lag and fully modified ordinary least squares econometric strategies on data from the Group of Seven (G7) countries from 1994 through 2016. We found long-term stability among the under-analysis variables. Notably, we revealed that while ETT shows a neutral effect in the short run, it promotes ecological sustainability in the long run. Likewise, increased globalization is also uncovered to foster ecological sustainability from the long-term perspective, though its neutral impact existed in the short term. In addition, energy intensity is found to increase ecological footprint consumption (EFCO); nevertheless, the phenomenon of the Environmental Kuznets Curve is valid for the G7 countries, suggesting a long-term ecological recovery in response to higher economic growth. Concerning causality directions, all variables established a bidirectional relationship with EFCO except for globalization, displaying a unidirectional link stemming from globalization to EFCO. From the normative policy perspective, ETT fiscal policy toolbox can prove a breakthrough instrument in mitigating environmental emissions, contributing to ecological quality. Also, in the face of enhanced globalization, exchanging green investment endeavors and trade in green and environmentally friendly products can achieve the ecological sustainability agenda of sustainable development.     

How can molecular biology contribute to the management of congenital adrenal hyperplasia?

The most common form of congenital adrenal hyperplasia is due to a deficiency of 21-hydroxylase (21OHD) activity and is caused by a mutation in the CYP21 gene. By genotyping patients, new and important information can be gained, including presence or absence of 21OHD in borderline cases, determining the severity of disease and identifying heterozygote carriers. Current management of patients with 21OHD involves administering sufficient glucocorticoids to suppress excess adrenal androgen secretion, but not so much that bone growth and mineralization are impaired. New management strategies have been proposed and include administering only substitution doses of corticosteroids and counteracting side-effects by administering an anti-androgen and aromatase inhibitor. Adrenalectomy has also been proposed. Further investigation into these approaches is necessary.     

How much do direct livestock emissions actually contribute to global warming?

Agriculture directly contributes about 10%–12% of current global anthropogenic greenhouse gas emissions, mostly from livestock. However, such percentage estimates are based on global warming potentials (GWPs), which do not measure the actual warming caused by emissions and ignore the fact that methane does not accumulate in the atmosphere in the same way as CO₂. Here, we employ a simple carbon cycle‐climate model, historical estimates and future projections of livestock emissions to infer the fraction of actual warming that is attributable to direct livestock non‐CO₂ emissions now and in future, and to CO₂ from pasture conversions, without relying on GWPs. We find that direct livestock non‐CO₂ emissions caused about 19% of the total modelled warming of 0.81°C from all anthropogenic sources in 2010. CO₂ from pasture conversions contributed at least another 0.03°C, bringing the warming directly attributable to livestock to 23% of the total warming in 2010. The significance of direct livestock emissions to future warming depends strongly on global actions to reduce emissions from other sectors. Direct non‐CO₂ livestock emissions would contribute only about 5% of the warming in 2100 if emissions from other sectors increase unabated, but could constitute as much as 18% (0.27°C) of the warming in 2100 if global CO₂ emissions from other sectors are reduced to near or below zero by 2100, consistent with the goal of limiting warming to well below 2°C. These estimates constitute a lower bound since indirect emissions linked to livestock feed production and supply chains were not included. Our estimates demonstrate that expanding the mitigation potential and realizing substantial reductions of direct livestock non‐CO₂ emissions through demand and supply side measures can make an important contribution to achieve the stringent mitigation goals set out in the Paris Agreement, including by increasing the carbon budget consistent with the 1.5°C goal.     

Does proximity to a mature forest contribute to the seed rain and recovery of an abandoned agriculture area in a semiarid climate?

Proximity to forests contributes to the recolonisation of anthropogenic‐disturbed areas through seed input. We evaluated the role of proximity to a mature forest in the recolonisation of an agricultural area that has been abandoned for 18 years and is currently a young forest. Seed rain was monitored at fixed distances from the mature forest. The type of surface recolonisation (germination versus resprouting) and the reproductive season were measured in both forests. The majority of plants recolonising the young forest originated from seed germination. Proximity to the mature forest contributed to the seed rain in the young forest; however, 18 years has not provided sufficient time for the recolonisation of 80 species present in the mature forest. Some species shared between forests differed in their fruiting season and seed dispersal. The seed rain had a total species richness of 56, a total density of 2270 seeds·m^?2·year^?1 and predominance of self‐ and wind dispersal. A significant reduction in seed rain with increasing distance from the mature forest was observed. The young forest contained 35 species not observed in the mature forest, and the floristic similarity between the two forests was 0.5, indicating that the two forests are floristically distinct.     

How do high-level specifications of the brain relate to variational approaches?

High-level specification of how the brain represents and categorizes the causes of its sensory input allows to link "what is to be done" (perceptual task) with "how to do it" (neural network calculation). In this article, we describe how the variational framework, which encountered a large success in modeling computer vision tasks, has some interesting relationships, at a mesoscopic scale, with computational neuroscience. We focus on cortical map computations such that "what is to be done" can be represented as a variational approach, i.e., an optimization problem defined over a continuous functional space. In particular, generalizing some existing results, we show how a general variational approach can be solved by an analog neural network with a given architecture and conversely. Numerical experiments are provided as an illustration of this general framework, which is a promising framework for modeling macro-behaviors in computational neuroscience.     

How do low horizontal forces produce disproportionately high torques in human locomotion?

Although horizontal ground forces are only approximately 15% of vertical forces, they account for 47% and 33% of the metabolic cost in walking and running. To explain these disproportionately high metabolic costs, we hypothesized that low horizontal ground forces generate relatively high torques on body segments during locomotion and this is mediated by long moment arms. We compared external force moment arms and discreet torques applied to the body segments by horizontal and vertical forces during walking and running. Sixteen subjects (21.9+/-1.9 years) walked at 1.5m/s and ten subjects (23.2+/-2.0 years) ran at 3.83 m/s. Segmental torques in the sagittal plane were partitioned into components due to horizontal and vertical forces and quantified by their angular impulses. The mean (+/-S.E.) ratios of horizontal to vertical ground forces (GF ratio) and angular impulses (AI ratio) in walking were 0.131 (+/-0.003, 95% confidence interval (CI) 0.124-0.137) and 0.530 (+/-0.018, CI 0.497-0.569). Results were similar in running. In both gaits the AI ratios were significantly greater than the GF ratios because the respective CI's did not overlap. The horizontal forces produced 53% and 41% as much angular impulse on the body segments, as did the vertical forces in walking and running despite being only 13% as large. In the two movements the moment arms for the horizontal forces averaged across foot, leg, thigh, and trunk body segments were 3.8 fold larger than those for the vertical forces. The data supported the hypothesis and suggest that the relatively low horizontal vs. vertical forces accounted for a disproportionately higher percentage of the angular impulses placed on the body segments and this effect was due to relatively long moment arms for horizontal forces. These results partially explain the relatively large metabolic cost of generating relatively low horizontal forces.     

How do tenascins influence the birth and life of a malignant cell?

Tenascins are large glycoproteins found in embryonic and adult extracellular matrices. Of the four family members, two have been shown to be overexpressed in the microenvironment of solid tumours: tenascin-C and tenascin-W. The regular presence of these proteins in tumours suggests a role in tumourigenesis, which has been investigated intensively for tenascin-C and recently for tenascin-W as well. In this review, we follow a malignant cell starting from its birth through its potential metastatic journey and describe how tenascin-C and tenascin-W contribute to these successive steps of tumourigenesis. We consider the importance of the mechanical aspect in tenascin signalling. Furthermore, we discuss studies describing tenascin-C as an important component of stem cell niches and present examples reporting its role in cancer therapy resistance.     

How close are we to a predictive science of the biosphere?

In just 20 years, the field of biosphere-atmosphere interactions has gone from a nascent discipline to a central area of modern climate change research. The development of terrestrial biosphere models that predict the responses of ecosystems to climate and increasing CO2 levels has highlighted several mechanisms by which changes in ecosystem composition and function might alter regional and global climate. However, results from empirical studies suggest that ecosystem responses can differ markedly from the predictions of terrestrial biosphere models. As I discuss here, the challenge now is to connect terrestrial biosphere models to empirical ecosystem measurements. Only by systematically evaluating the predictions of terrestrial biosphere models against suites of ecosystem observations and experiments measurements will a true predictive science of the biosphere be achieved.     

Does vertical transmission contribute to the prevalence of toxoplasmosis?

Toxoplasma gondii is a ubiquitous parasite with a widespread distribution both in terms of geographical and host range. Although the definitive host is the cat, it is also a major health hazard to domestic animals and humans. Three routes of transmission are recognised (infection from the cat, carnivory and congenital transmission). We aimed to assess the relative importance of congenital transmission, using sheep as a model system, due to the lack of carnivory. We report, using PCR as a diagnostic tool, that congenital transmission occurs with high frequency (69%). If transmission from oocysts was important in sheep, we would expect sheep reared under the same environmental conditions (i.e. a single farm) to have a random distribution of Toxoplasma infection. Using breeding records in conjunction with PCR, some families were found to have high Toxoplasma prevalence and abortion while others were free of Toxoplasma infection and abortion (P < 0.01). This supports the notion that Toxoplasma may be transmitted vertically. In humans, we conducted a similar study and showed that Toxoplasma was transmitted from mother to baby in 19.8% of cases. Vertical transmission in Toxoplasma may be more important than previously thought and this knowledge should be considered in any eradication strategies.     

How do Bax and Bak lead to permeabilization of the outer mitochondrial membrane?

Bcl-2 family members, like the structurally similar translocation domain of diphtheria toxin, can form ion-selective channels and larger-diameter pores in artificial lipid bilayers. Recent studies show how Bcl-2 family members change topology in membranes during apoptosis and that these different states may either promote or inhibit apoptosis. Binding of BH3-only proteins alters the subcellular localization and/or membrane topology and probably affects the channel formation of Bcl-2, Bcl-xL and Bcl-w. However, it remains unclear how the pore-forming activity functions in cells to regulate mitochondrial membrane permeabilization and cell death. Bcl-2 family members in flies and worms regulate apoptosis by mechanisms seemingly unrelated to membrane permeabilization, leaving a unifying model for the biochemical activity of this protein family unknown. Work linking Bcl-2 family members to mitochondrial morphogenesis in worms and mammals suggests some common functions of Bcl-2 family proteins may exist.     

Back to translation: removal of aIF2 from the 5′-end of mRNAs by translation recovery factor in the crenarchaeon Sulfolobus solfataricus

The translation initiation factor aIF2 of the crenarchaeon Sulfolobus solfataricus (Sso) recruits initiator tRNA to the ribosome and stabilizes mRNAs by binding via the γ-subunit to their 5′-triphosphate end. It has been hypothesized that the latter occurs predominantly during unfavorable growth conditions, and that aIF2 or aIF2-γ is released on relief of nutrient stress to enable in particular anew translation of leaderless mRNAs. As leaderless mRNAs are prevalent in Sso and aIF2-γ bound to the 5′-end of a leaderless RNA inhibited ribosome binding in vitro, we aimed at elucidating the mechanism underlying aIF2/aIF2-γ recycling from mRNAs. We have identified a protein termed Trf (translation recovery factor) that co-purified with trimeric aIF2 during outgrowth of cells from prolonged stationary phase. Subsequent in vitro studies revealed that Trf triggers the release of trimeric aIF2 from RNA, and that Trf directly interacts with the aIF2-γ subunit. The importance of Trf is further underscored by an impaired protein synthesis during outgrowth from stationary phase in a Sso trf deletion mutant.     

Does estrogen contribute to the hepatic regeneration following portal branch ligation in rats?

The aim of this study was to determine whether estrogen plays any role in the hepatic regeneration of nonligated lobe following portal branch ligation (PBL). Male rats were subjected to PBL on the left and middle lobes. Two and 7 days after PBL, the rats were killed and blood and liver samples were analyzed. Sham animals underwent only laparotomy. The serum estradiol levels were significantly elevated on day 2 following PBL and returned to normal levels on day 7. The expression of estrogen receptors (ER) in the liver evaluated by Western blotting did not show any change in the nonligated lobe compared with shams. Immunohistochemical study for ER showed a predominant ER expression in the hepatocyte nucleus in periportal area (zone 1), although there was no apparent difference in the amount and expression pattern between sham and PBL. However, chronic inhibition of ER by an ER antagonist (ICI 182,780) showed a significantly lower regeneration rate of the nonligated lobe compared with vehicle treatment. Liver regeneration-associated genes also were less activated in the ICI group. Moreover, portal venous flow, determined by fluorescent microsphere injection, was significantly lower in the ICI group compared with vehicle group. These changes correlated with the attenuated expression of endothelial nitric oxide synthase mRNA in both superior mesenteric arteries and veins. In conclusion, these results indicate that the estrogen's contribution on hepatic regeneration following PBL is at least partly mediated through maintaining mesenteric blood flow by mesenteric endothelial nitric oxide synthase upregulation rather than directly activating liver regeneration in the liver.     

Can phosphorus limitation contribute to the maintenance of sex? A test of a key assumption

Why sex is so common remains unclear; what is certain is that the predominance of sex despite its profound costs means that it must confer major advantages. Here, we use elemental and nucleic acid assays to evaluate a key element of a novel, integrative hypothesis considering whether sex might be favoured because of differences in body composition between sexuals and asexuals. We found that asexual Potamopyrgus antipodarum, a New Zealand snail, have markedly higher bodily phosphorus and nucleic acid content per unit mass than sexual counterparts. These differences coincide with and are almost certainly linked to the higher ploidy of the asexuals. Our results are the first documented body composition differences between sexual and asexual organisms, and the first detected phenotypic difference between sexual and asexual P. antipodarum, an important natural model system for the study of the maintenance of sex. These findings also verify a central component of our hypothesis that competition between diploid sexuals and polyploid asexuals could be influenced by phosphorus availability.     

How to prove the existence of metabolons?

Sequential enzymes in biosynthetic pathways are organized in metabolons. It is challenging to provide experimental evidence for the existence of metabolons as biosynthetic pathways are composed of highly dynamic protein–protein interactions. Many different methods are being applied, each with strengths and weaknesses. We will present and evaluate several techniques that have been applied in providing evidence for the orchestration of the biosynthetic pathways of cyanogenic glucosides and glucosinolates in metabolons. These evolutionarily related pathways have ER-localized cytochromes P450 that are proposed to function as anchoring site for assembly of the enzymes into metabolons. Additionally, we have included commonly used techniques, even though they have not been used (yet) on these two pathways. In the review, special attention will be given to less-exploited fluorescence-based methods such as FCS and FLIM. Ultimately, understanding the orchestration of biosynthetic pathways may contribute to successful engineering in heterologous hosts.