Innate immune responses to Chlamydia pneumoniae infection: role of TLRs,NLRs, and the inflammasome

Chlamydiae are important human pathogens that are responsible for a wide rage of diseases with a significant impact on public health. In this review article we highlight how recent studies have increased our knowledge of Chlamydia pneumoniae pathogenesis and mechanisms of innate immunity directed host defense against C. pneumoniae infection.     

Two new Mio-Pliocene Chadian hominids enlighten Charles Darwin's 1871 prediction

The idea of an evolutionary sequence for humans is quite recent. Over the last 150 years, we have discovered unexpected ancestors, numerous close relatives and our deep evolutionary roots in Africa. In the last decade, three Late Miocene hominids have been described, two about 6 Ma (Ardipithecus and Orrorin) in East Africa and the third dated to about 7 Ma (Sahelanthropus) in Central Africa. The specimens are too few to propose definite relationship to other species, but clearly these belong to a new evolutive grade distinct from Australopithecus and Homo. Moreover, all of them were probably habitual bipeds and lived in woodlands, thus falsifying the savannah hypothesis of human origins. In light of all this recent knowledge, Charles Darwin predicted correctly in 1871 that Africa is the birthplace of humans, chimpanzees and our close relatives.     

Intermediates generated during the reaction of reduced Rhodobacter sphaeroides cytochrome c oxidase with dioxygen

Cytochrome oxidase is one of the functionally most intriguing redox-driven proton pumps. During the last decade our increased understanding of the system has greatly benefited from theoretical calculations and modeling in the framework of three-dimensional structures of cytochrome c oxidases from different species. Because these studies are based on results from experiments, it is important that any ambiguities in the conclusions extracted from these experiments are discussed and elucidated. In a recent study Szundi et al. (Szundi et al. Biochemistry 2012, 51, 9302) investigated the reaction of the reduced Rhodobacter sphaeroides cytochrome c oxidase with O₂ and arrived at conclusions different from those derived from earlier investigations. In this short communication we compare these very recent data to those obtained from earlier studies and discuss the origin of the differences.     

AMBRA1: When autophagy meets cell proliferation

A growing amount of evidence reported in the literature in recent years strongly supports the relevance of the interplay between autophagy and other pathways. In this context, the study of the link between autophagy and cell proliferation regulation has been among the most challenging. In our recent publications, we finely characterize a role for the pro-autophagic protein AMBRA1 in the regulation of cell proliferation. AMBRA1 modulates autophagy and interacts with PPP2/PP2A (protein phosphatase 2), thus also modulating MYC protein levels and the cell proliferation rate. Interestingly, this pathway of regulation is controlled by the master regulator of autophagy and cell growth, MTORC1. Notably, in our study we demonstrate the relevance of the AMBRA1-mediated regulation of MYC in tumorigenesis, also identifying AMBRA1 as a tumor suppressor gene.     

Structural determinants of plant peroxidase function

The classical plant peroxidases are a well-studied group of heme-containing enzymes for which many different functions have been proposed. In the majority of plant species investigated they occur as distinctive isoenzymes which can be constitutive or induced in response to external factors such as wounding, stress and attack by pathogens. More than 70 peroxidase isoenzymes are predicted to occur in Arabidopsis thaliana alone, according to recent analysis of the complete peroxidase gene family of this model plant. Understanding this enzymatic diversity and its functional significance is a major focus of structural and mechanistic studies of plant peroxidases. The three-dimensional structures of plant peroxidases from Arabidopsis, barley, horseradish, peanut and soybean have now been determined by X-ray crystallography together with the structures of several catalytic intermediates and substrate complexes that are relevant to enzyme function. On this basis, specific roles for particular amino acid residues and structural motifs or regions have been proposed or in some cases, confirmed. Some of these have been investigated experimentally using site-directed mutagenesis and other techniques. An overview of recent developments will be presented that reflects our current understanding of structure and function in this important group of enzymes.     

Mathematical Models Light Up Plant Signaling

Plants respond to changes in the environment by triggering a suite of regulatory networks that control and synchronize molecular signaling in different tissues, organs, and the whole plant. Molecular studies through genetic and environmental perturbations, particularly in the model plant Arabidopsis thaliana, have revealed many of the mechanisms by which these responses are actuated. In recent years, mathematical modeling has become a complementary tool to the experimental approach that has furthered our understanding of biological mechanisms. In this review, we present modeling examples encompassing a range of different biological processes, in particular those regulated by light. Current issues and future directions in the modeling of plant systems are discussed.     

Streptomycetes: Surrogate hosts for the genetic manipulation of biosynthetic gene clusters and production of natural products

Due to the worldwide prevalence of multidrug-resistant pathogens and high incidence of diseases such as cancer, there is an urgent need for the discovery and development of new drugs. Nearly half of the FDA-approved drugs are derived from natural products that are produced by living organisms, mainly bacteria, fungi, and plants. Commercial development is often limited by the low yield of the desired compounds expressed by the native producers. In addition, recent advances in whole genome sequencing and bioinformatics have revealed an abundance of cryptic biosynthetic gene clusters within microbial genomes. Genetic manipulation of clusters in the native host is commonly used to awaken poorly expressed or silent gene clusters, however, the lack of feasible genetic manipulation systems in many strains often hinders our ability to engineer the native producers. The transfer of gene clusters into heterologous hosts for expression of partial or entire biosynthetic pathways is an approach that can be used to overcome this limitation. Heterologous expression also facilitates the chimeric fusion of different biosynthetic pathways, leading to the generation of “unnatural” natural products. The genus Streptomyces is especially known to be a prolific source of drugs/antibiotics, its members are often used as heterologous expression hosts. In this review, we summarize recent applications of Streptomyces species, S. coelicolor, S. lividans, S. albus, S. venezuelae and S. avermitilis, as heterologous expression systems.     

Galectin-9 in physiological and pathological conditions

We first cloned galectin-9 (Gal-9)/ecalectin as a T cell-derived eosinophil chemoattractant. Gal-9 plays a role in not only accumulation but also activation of eosinophils in experimental allergic models and human allergic patients, because Gal-9 induces eosinophil chemoattraction in vitro and in vivo and activates eosinophils in many aspects. Gal-9 requires divalent galactoside-binding activity but not the linker peptide of Gal-9 to exhibit its biological functions, and an unidentified matrix metalloproteinase is involved in the release of Gal-9. Our recent studies also showed that Gal-9 has other functions, such as cell differentiation, aggregation, adhesion, and death. Now, we and other groups are on the way of investigating the regulation and function of Gal-9 in a variety of physiological and pathological conditions. In this article, we will show the possible role of Gal-9 in physiological and pathological conditions by using our recent findings. Published in 2004.     

Fungal (-like) biocontrol organisms in tomato disease control

The worldwide important crop tomato is attacked by various pathogens, for which management is still primarily reliant on fungicides despite increasing concerns and constraints on their use. Other approaches are investigated, including the use of biocontrol organisms to manage tomato diseases. In this review we discuss and compare the interaction of major biocontrol fungi (BCF) with tomato, including the endophytic arbuscular mycorrhizal fungi and Piriformospora indica, the free-living opportunistic symbionts Trichoderma spp. and non-pathogenic Fusarium oxysporum, as well as the oomycete Pythium oligandrum. We cover recent advances that have been made in unraveling biocontrol modes of action against the most important tomato pathogens, encompassing direct effects of the BCF on pathogens and their indirect effects through the plant, with a main focus on induced systemic resistance. It is an exciting era for the study of biocontrol tripartite interactions, with the emergence of next-generation sequencing tools and the higher pace at which new genomes are being sequenced nowadays, as was recently also achieved for tomato. In addition, plant pathology and biocontrol research domains are increasingly reaching out to each other, because of the parallels that we are only beginning to discover between the interactions of beneficial and detrimental micro-organisms with a plant. Considering the enormous technological possibilities at hand today, this seems a timely opportunity to review the most recent advances in this field and to anticipate to what is ahead of us, discussing breakthroughs expected in our understanding of biocontrol interactions and remaining hurdles on the way to reach them.     

The roles of autophagy in development and stress responses in Arabidopsis thaliana

Autophagy is a dynamic process that involves the recycling process of the degradation of intracellular materials. Over the past decade, our molecular and physiological understanding of plant autophagy has greatly been increased. Most essential autophagic machineries are conserved from yeast to plants. The roles that autophagy-related genes (ATGs) family play in the lifecycle of the Arabidopsis are proved to be similar to that in mammal. Autophagy is activated during certain stages of development, senescence or in response to starvation, or environmental stress in Arabidopsis. In the progression of autophagy, ATGs act as central signaling regulators and could develop sophisticated mechanisms to survive when plants are suffering unfavorable environments. It will facilitate further understanding of the molecular mechanisms of autophagy in plant. In this review, we will discuss recent advances in our understanding of autophagy in Arabidopsis, areas of controversy, and highlight potential future directions in autophagy research.     

Detection of hard and soft selective sweeps from Drosophila melanogaster population genomic data

Whether hard sweeps or soft sweeps dominate adaptation has been a matter of much debate. Recently, we developed haplotype homozygosity statistics that (i) can detect both hard and soft sweeps with similar power and (ii) can classify the detected sweeps as hard or soft. The application of our method to population genomic data from a natural population of Drosophila melanogaster (DGRP) allowed us to rediscover three known cases of adaptation at the loci Ace, Cyp6g1, and CHKov1 known to be driven by soft sweeps, and detected additional candidate loci for recent and strong sweeps. Surprisingly, all of the top 50 candidates showed patterns much more consistent with soft rather than hard sweeps. Recently, Harris et al. 2018 criticized this work, suggesting that all the candidate loci detected by our haplotype statistics, including the positive controls, are unlikely to be sweeps at all and that instead these haplotype patterns can be more easily explained by complex neutral demographic models. They also claim that these neutral non-sweeps are likely to be hard instead of soft sweeps. Here, we reanalyze the DGRP data using a range of complex admixture demographic models and reconfirm our original published results suggesting that the majority of recent and strong sweeps in D. melanogaster are first likely to be true sweeps, and second, that they do appear to be soft. Furthermore, we discuss ways to take this work forward given that most demographic models employed in such analyses are necessarily too simple to capture the full demographic complexity, while more realistic models are unlikely to be inferred correctly because they require a large number of free parameters.     

A Microscopic Formulation for the Actin-Driven Motion of Listeria in Curved Paths

Using a generalized Brownian ratchet model that accounts for the interactions of actin filaments with the surface of Listeria mediated by proteins like ActA and Arp2/3, we have developed a microscopic model for the movement of Listeria. Specifically, we show that a net torque can be generated within the comet tail, causing the bacteria to spin about its long axis, which in conjunction with spatially varying polymerization at the surface leads to motions of bacteria in curved paths that include circles, sinusoidal-like curves, translating figure eights, and serpentine shapes, as observed in recent experiments. A key ingredient in our formulation is the coupling between the motion of Listeria and the force-dependent rate of filament growth. For this reason, a numerical scheme was developed to determine the kinematic parameters of motion and stress distribution among filaments in a self-consistent manner. We find that a 5-15% variation in polymerization rates can lead to radii of curvatures of the order of 4-20 μm, measured in experiments. In a similar way, our results also show that most of the observed trajectories can be produced by a very low degree of correlation, <10%, among filament orientations. Since small fluctuations in polymerization rate, as well as filament orientation, can easily be induced by various factors, our findings here provide a reasonable explanation for why Listeria can travel along totally different paths under seemingly identical experimental conditions. Besides trajectories, stress distributions corresponding to different polymerization profiles are also presented. We have found that although some actin filaments generate propelling forces that push the bacteria forward, others can exert forces opposing the movement of Listeria, consistent with recent experimental observations.     

Specific developmental pathways underlie host specificity in the parasitic plant Orobanche

Parasitic angiosperms are an ecologically and economically important group of plants. However our understanding of the basis for host specificity in these plants is embryonic. Recently we investigated host specificity in the parasitic angiosperm Orobanche minor, and demonstrated that this host generalist parasite comprises genetically defined races that are physiologically adapted to specific hosts. Populations occurring naturally on red clover (Trifolium pratense) and sea carrot (Daucus carota subsp. gummifer) respectively, showed distinct patterns of host specificity at various developmental stages, and a higher fitness on their natural hosts, suggesting these races are locally adapted. Here we discuss the implications of our findings from a broader perspective. We suggest that differences in signal responsiveness and perception by the parasite, as well as qualitative differences in signal production by the host, may elicit host specificity in this parasitic plant. Together with our earlier demonstration that these O. minor races are genetically distinct based on molecular markers, our recent data provide a snapshot of speciation in action, driven by host specificity. Indeed, host specificity may be an underestimated catalyst for speciation in parasitic plants generally. We propose that identifying host specific races using physiological techniques will complement conventional molecular marker-based approaches to provide a framework for delineating evolutionary relationships among cryptic host-specific parasitic plants.Key words: host specificity, parasitic plant, broomrape, orobanche, speciation     

Arabidopsis ACBP1 overexpressors are Pb(II)-tolerant and accumulate Pb(II)

In our recent paper in the Plant Journal, we demonstrated that Arabidopsis thaliana acyl-CoA-binding protein ACBP1 binds lead [Pb(II)], its mRNA is induced by Pb(II)-treatment and transgenic Arabidopsis overexpressing ACBP1 are conferred Pb(II) tolerance and accumulate Pb(II). Our results suggest that ACBP1 overexpressors are potentially useful for applications in phytoremediation. Since very few plant proteins that bind and accumulate Pb(II) have been identified, our findings provide a feasible method in phytoremediating Pb(II).Key words: acyl-CoA-binding proteins, heavy metals, Pb(II) accumulation, phytoremediation, plasma membrane     

Leveraging coordination chemistry to visualize metal ions via photoacoustic imaging

Metal ions are indispensable to all living systems owing to their diverse roles. Perturbation of metal homeostasis have been linked to many pathological conditions. As such, visualizing metal ions in these complex environments are of utmost importance. Photoacoustic imaging is a promising modality that combines the sensitivity of fluorescence to the superior resolution of ultrasound, through a light-in sound-out process, making it an appealing modality for metal ion detection in vivo. In this review, we highlight recent advances in the development of photoacoustic imaging probes for in vivo detection of metal ions, such as potassium, copper, zinc, and palladium. In addition, we provide our perspective and outlook on the exciting field.     

Distribution and seasonal dynamics of Cryptomonads in Sicilian water bodies

Several species with a relevant ecological importance belong to Cryptophyta. Nevertheless, species-level identification from microscopic observations is problematic, lacking recent taxonomic keys. In this study we report our observations on distribution and seasonal dynamics of Cryptomonads in 33 Sicilian water bodies, as well as the main taxonomical problems we encountered. Species of the genera Cryptomonas and Plagioselmis are the most common in the examined water bodies. Their biomass seasonal trends usually show a peak in late winter and early spring. In advanced spring, and also in summer, due to the higher grazing pressure, the Cryptomonads biomass reaches its lowest values. Moreover, in a small, eutrophic, temporary pond (Santa Rosalia), without grazing pressure in spring, the Cryptomonads bloomed in summer. From our results, we propose to focus the attention on the sensitiveness of these organisms to filter feeding to explain their seasonal dynamics.     

Evolution and systematics of the feliform Carnivora

Recent studies have improved our knowledge about the evolution and phylogeny of feliform taxa. Detailed study on new fossil remains of extinct feliform nimravides allows a new hypothesis concerning interrelationships within this family. Many factors indicate lack of sister relationships of Nimravinae and Barbourofelinae. However, only further investigations may bring full acceptance of this hypothesis. The paraphyly of Viverridae has been resolved by excluding the taxa Nandinia, Prionodon and Cryptoprocta and Fossa, which today are placed basally to all remaining Feliformia (family Nandiniidae), as sister taxon of Felidae (family Prionodontidae) and as Malagasy Carnivora lineage basal to hyaenid–herpestid clade, respectively. Still, incongruence among results concerning the systematic position of these taxa exhibits the necessity of further investigation. Detailed study revealed inconsistencies within genet and genet-like taxa phylogeny, which have still to be resolved. Malagasy Carnivora belong to a separate lineage, which originated from herpestid–hyaenid ancestors and colonised Madagascar during a single colonisation event. However, interrelationships among Malagasy Carnivora are poorly resolved. The situation of the social mongooses clade was resolved by including ethologic data to phylogenetic analyses; however, there is little information on solitary mongooses, which have a paraphyletic status today. Felid morphology and taxonomic revision attained during recent years show greater evolutionary differentiation. Nevertheless, no clear taxonomy has been achieved. New investigating methods are required. In the hyaenid family, which includes only four living species, some investigations related to the ecomorphological evolutionary path have been performed. The comparisons of fossil and subfossil remains with modern feliforms, combined with recent molecular methods, may improve our knowledge.