A Transcriptome-Wide Analysis of Psoriasis: Identifying the Potential Causal Genes and Drug Candidates.

Psoriasis is a chronic inflammatory skin disease characterized by cutaneous eruptions and pruritus. Because the genetic backgrounds of psoriasis are only partially revealed, an integrative and rigorous study is necessary. We conducted a transcriptome-wide association study (TWAS) with the new Genotype-Tissue Expression version 8 reference panels, including some tissue and multi-tissue panels that were not used previously. We performed tissue-specific heritability analyses on genome-wide association study data to prioritize the tissue panels for TWAS analysis. TWAS and colocalization (COLOC) analyses were performed with eight tissues from the single-tissue panels and the multi-tissue panels of context-specific genetics (CONTENT) to increase tissue specificity and statistical power. From TWAS, we identified the significant associations of 101 genes in the single-tissue panels and 64 genes in the multi-tissue panels, of which 26 genes were replicated in the COLOC. Functional annotation and network analyses identified that the genes were associated with psoriasis and/or immune responses. We also suggested drug candidates that interact with jointly significant genes through a conditional and joint analysis. Together, our findings may contribute to revealing the underlying genetic mechanisms and provide new insights into treatments for psoriasis.

Function of cell adhesion molecules in differentiation of ray sensory neurons in C. elegans.

For proper functioning of the nervous system, it is crucial that neurons find their appropriate partners and build the correct neural connection patterns. Although cell adhesion molecules (CAMs) have been studied for many years as essential players in neural connections, we have yet to unravel the code by which CAMs encode synaptic specificity. We analyzed the effects of mutations in CAM genes on the morphology and synapses of a set of sensory neurons in the Caenorhabditis elegans male tail. B-type ray sensory neurons express 10 genes encoding CAMs. We examined the effect on axon trajectory and localization of pre-synaptic components in viable mutants of nine of these. We found axon trajectory defects in mutants of UNC-40/DCC, SAX-3/ROBO, and FMI-1/Flamingo/Celsr1. None of the mutations caused loss of pre-synaptic components in axons, and in several the level even appeared to increase, suggesting possible accumulation of pre-synapses. B-type sensory neurons fasciculate with a second type of ray sensory neuron, the A-type, in axon commissures. We found a CAM expressed in A-type functions additively with a CAM expressed in B-type in axon guidance, and lack of a CAM expressed in B-type affected A-type axon guidance. Overall, single and multiple mutants of CAM genes had limited effects on ray neuron trajectories and accumulation of synaptic components.

Anatomical and Functional Differences in the Sex-Shared Neurons of the Nematode C. elegans.

Studies on sexual dimorphism in the structure and function of the nervous system have been pivotal to understanding sex differences in behavior. Such studies, especially on invertebrates, have shown the importance of neurons specific to one sex (sex-specific neurons) in shaping sexually dimorphic neural circuits. Nevertheless, recent studies using the nematode C. elegans have revealed that the common neurons that exist in both sexes (sex-shared neurons) also play significant roles in generating sex differences in the structure and function of neural circuits. Here, we review the anatomical and functional differences in the sex-shared neurons of C. elegans. These sexually dimorphic characteristics include morphological differences in neurite projection or branching patterns with substantial changes in synaptic connectivity, differences in synaptic connections without obvious structural changes, and functional modulation in neural circuits with no or minimal synaptic connectivity changes. We also cover underlying molecular mechanisms whereby these sex-shared neurons contribute to the establishment of sexually dimorphic circuits during development and function differently between the sexes.

Direct glia-to-neuron transdifferentiation gives rise to a pair of male-specific neurons that ensure nimble male mating.

Sexually dimorphic behaviours require underlying differences in the nervous system between males and females. The extent to which nervous systems are sexually dimorphic and the cellular and molecular mechanisms that regulate these differences are only beginning to be understood. We reveal here a novel mechanism by which male-specific neurons are generated in Caenorhabditis elegans through the direct transdifferentiation of sex-shared glial cells. This glia-to-neuron cell fate switch occurs during male sexual maturation under the cell-autonomous control of the sex-determination pathway. We show that the neurons generated are cholinergic, peptidergic, and ciliated putative proprioceptors which integrate into male-specific circuits for copulation. These neurons ensure coordinated backward movement along the mate's body during mating. One step of the mating sequence regulated by these neurons is an alternative readjustment movement performed when intromission becomes difficult to achieve. Our findings reveal programmed transdifferentiation as a developmental mechanism underlying flexibility in innate behaviour.

Neurite Branching Regulated by Neuronal Cell Surface Molecules in Caenorhabditis elegans.

The high synaptic density in the nervous system results from the ability of neurites to branch. Neuronal cell surface molecules play central roles during neurite branch formation. The underlying mechanisms of surface molecule activity have often been elucidated using invertebrates with simple nervous systems. Here, we review recent advances in understanding the molecular mechanisms of neurite branching in the nematode Caenorhabditis elegans. We discuss how cell surface receptor complexes link to and modulate actin dynamics to regulate dendritic and axonal branch formation. The mechanisms of neurite branching are often coupled with other neural circuit developmental processes, such as synapse formation and axon guidance, via the same cell-cell surface molecular interactions. We also cover ectopic and sex-specific neurite branching in C. elegans in an attempt to illustrate the importance of these studies in contributing to our understanding of conserved cell surface molecule regulation of neurite branch formation.

Expressional artifact caused by a co-injection marker rol-6 in C. elegans.

In transgenic research, selection markers have greatly facilitated the generation of transgenic animals. A prerequisite for a suitable selection marker to be used along with a test gene of interest is that the marker should not affect the phenotype of interest in transformed animals. One of the most common selection markers used in C. elegans transgenic approaches is the rol-6 co-injection marker, which induces a behavioral roller phenotype due to a cuticle defect but is not known to have other side effects. However, we found that the rol-6 co-injection marker can cause expression of GFP in the test sequence in a male-specific interneuron called CP09. We found that the rol-6 gene sequence included in the marker plasmid is responsible for this unwanted expression. Accordingly, the use of the rol-6 co-injection marker is not recommended when researchers intend to examine precise expression or perform functional studies especially targeting male C. elegans neurons. The rol-6 sequence region we identified can be used to drive a specific expression in CP09 neuron for future research.

Evolutionarily conserved and divergent functions for cell adhesion molecules in neural circuit assembly.

The developing nervous system generates remarkably precise synaptic connections between neurons and their postsynaptic target cells. Numerous neural cell adhesion proteins have been identified to mediate cell recognition between synaptic partners in several model organisms. Here, I review the role of protein interactions of cell adhesion molecules in neural circuit assembly and address how these interactions are utilized to form different neural circuitries in different species. The emerging evidence suggests that the extracellular trans-interactions of cell adhesion proteins for neural wiring are evolutionarily conserved across taxa, but they are often used in different steps of circuit assembly. I also highlight how these conserved protein interactions work together as a group to specify neural connectivity.

The Ancient Phosphatidylinositol 3-Kinase Signaling System Is a Master Regulator of Energy and Carbon Metabolism in Algae.

Algae undergo a complete metabolic transformation under stress by arresting cell growth, inducing autophagy and hyper-accumulating biofuel precursors such as triacylglycerols and starch. However, the regulatory mechanisms behind this stress-induced transformation are still unclear. Here, we use biochemical, mutational, and "omics" approaches to demonstrate that PI3K signaling mediates the homeostasis of energy molecules and influences carbon metabolism in algae. In Chlamydomonas reinhardtii, the inhibition and knockdown (KD) of algal class III PI3K led to significantly decreased cell growth, altered cell morphology, and higher lipid and starch contents. Lipid profiling of wild-type and PI3K KD lines showed significantly reduced membrane lipid breakdown under nitrogen starvation (-N) in the KD. RNA-seq and network analyses showed that under -N conditions, the KD line carried out lipogenesis rather than lipid hydrolysis by initiating de novo fatty acid biosynthesis, which was supported by tricarboxylic acid cycle down-regulation and via acetyl-CoA synthesis from glycolysis. Remarkably, autophagic responses did not have primacy over inositide signaling in algae, unlike in mammals and vascular plants. The mutant displayed a fundamental shift in intracellular energy flux, analogous to that in tumor cells. The high free fatty acid levels and reduced mitochondrial ATP generation led to decreased cell viability. These results indicate that the PI3K signal transduction pathway is the metabolic gatekeeper restraining biofuel yields, thus maintaining fitness and viability under stress in algae. This study demonstrates the existence of homeostasis between starch and lipid synthesis controlled by lipid signaling in algae and expands our understanding of such processes, with biotechnological and evolutionary implications.

Influence of Water Depth on Microalgal Production, Biomass Harvest, and Energy Consumption in High Rate Algal Pond Using Municipal Wastewater.

The high rate algal ponds (HRAP) powered and mixed by a paddlewheel have been widely used for over 50 years to culture microalgae for the production of various products. Since light incidence is limited to the surface, water depth can affect microalgal growth in HRAP. To investigate the effect of water depth on microalgal growth, a mixed microalgal culture constituting three major strains of microalgae including Chlorella sp., Scenedesmus sp., and Stigeoclonium sp. (CSS), was grown at different water depths (20, 30, and 40 cm) in the HRAP, respectively. The HRAP with 20cm of water depth had about 38% higher biomass productivity per unit area (6.16 ± 0.33 g·m⁻²·d⁻¹) and required lower nutrients and energy consumption than the other water depths. Specifically, the algal biomass of HRAP under 20c m of water depth had higher settleability through larger floc size (83.6% settleability within 5 min). These results indicate that water depth can affect the harvesting process as well as cultivation of microalgae. Therefore, we conclude that water depth is an important parameter in HRAP design for mass cultivation of microalgae.

Application of high-salinity stress for enhancing the lipid productivity of Chlorella sorokiniana HS1 in a two-phase process.

Increased lipid accumulation of algal cells as a response to environmental stress factors attracted much attention of researchers to incorporate this stress response into industrial algal cultivation process with the aim of enhancing algal lipid productivity. This study applies high-salinity stress condition to a two-phase process in which microalgal cells are initially grown in freshwater medium until late exponential phase and subsequently subjected to high-salinity condition that induces excessive lipid accumulation. Our initial experiment revealed that the concentrated culture of Chlorella sorokiniana HS1 exhibited the intense fluorescence of Nile red at the NaCl concentration of 60 g/L along with 1 g/L of supplemental bicarbonate after 48 h of induction period without significantly compromising cultural integrity. These conditions were further verified with the algal culture grown for 7 days in a 1 L bottle reactor that reached late exponential phase; a 12% increment in the lipid content of harvested biomass was observed upon inducing high lipid accumulation in the concentrated algal culture at the density of 5.0 g DW/L. Although an increase in the sum of carbohydrate and lipid contents of harvested biomass indicated that the external carbon source supplemented during the induction period increased overall carbon assimilation, a decrease in carbohydrate content suggested the potential reallocation of cellular carbon that promoted lipid droplet formation under high-salinity stress. These results thus emphasize that the two-phase process can be successfully implemented to enhance algal lipid productivity by incorporating high-salinity stress conditions into the pre-concentrated sedimentation ponds of industrial algal production system.

Multiple conserved cell adhesion protein interactions mediate neural wiring of a sensory circuit in C. elegans.

Nervous system function relies on precise synaptic connections. A number of widely-conserved cell adhesion proteins are implicated in cell recognition between synaptic partners, but how these proteins act as a group to specify a complex neural network is poorly understood. Taking advantage of known connectivity in C. elegans, we identified and studied cell adhesion genes expressed in three interacting neurons in the mating circuits of the adult male. Two interacting pairs of cell surface proteins independently promote fasciculation between sensory neuron HOA and its postsynaptic target interneuron AVG: BAM-2/neurexin-related in HOA binds to CASY-1/calsyntenin in AVG; SAX-7/L1CAM in sensory neuron PHC binds to RIG-6/contactin in AVG. A third, basal pathway results in considerable HOA-AVG fasciculation and synapse formation in the absence of the other two. The features of this multiplexed mechanism help to explain how complex connectivity is encoded and robustly established during nervous system development.

Microalgal diversity fosters stable biomass productivity in open ponds treating wastewater.

It is established that biodiversity determines productivity of natural ecosystems globally. We have proved that abiotic factors influenced biomass productivity in engineered ecosystems i.e. high rate algal ponds (HRAPs), previously. This study demonstrates that biotic factors, particularly microalgal diversity, play an essential role in maintaining stable biomass productivity in HRAP treating municipal wastewater by mutualistic adaptation to environmental factors. The current study examined data from the second year of a two-year study on HRAP treating municipal wastewater. Microalgal diversity, wastewater characteristics, treatment efficiency and several environmental and meteorological factors were documented. Multivariate statistical analyses reveal that microalgae in uncontrolled HRAPs adapt to adverse environmental conditions by fostering diversity. Subsequently, five dominant microalgal strains by biovolume were isolated, enriched, and optimum conditions for high biomass productivity were ascertained. These laboratory experiments revealed that different microalgal strains dominate in different conditions and a consortium of these diverse taxa help in sustaining the algae community from environmental and predatory pressures. Diversity, niche or seasonal partitioning and mutualistic growth are pertinent in microalgal cultivation or wastewater treatment. Therefore, enrichment of selective species would deprive the collective adaptive ability of the consortium and encourage system vulnerability especially in wastewater treatment.

Gene Function Prediction Based on Developmental Transcriptomes of the Two Sexes in C. elegans.

We compare whole-animal RNA-seq transcriptomes for C. elegans males and hermaphrodites from the late L3 larval stage to young adulthood. During this interval, male sexual structures develop, including extensive neurogenesis and synaptogenesis that nearly doubles the size of the nervous system. Previous genome-wide expression studies in C. elegans have usually focused on only one sex-the hermaphrodite-and there are a relatively large number of genes that remain without meaningful annotation. In the present study, differential expression analysis of the RNA-seq data revealed 1,751 genes expressed at a higher level in the male. By differential expression and co-expression analyses, we identified transcription factors required for differentiation of male genital structures, semen proteins, and candidates for components of synapse function. Comparison with other prediction tools suggests that our dataset can expand gene predictions. The results validate the dataset as a rich resource for future gene discovery in C. elegans.

BOULE, a Deleted in Azoospermia Homolog, Is Recruited to Stress Granules in the Mouse Male Germ Cells.

High temperature adversely affects normal development of male germ cells in mammals. Acute heat stress induces the formation of stress granules (SGs) in a set of male germ cells, and the SGs have been proposed to protect those cells from heat-induced apoptosis. DAZL, one of DAZ (Deleted in Azoospermia) family proteins, was shown to be an essential component of SGs, which is required for SG formation in the mouse testis. In the present study, we asked whether BOULE, the founding member of DAZ family proteins, is a component of the SGs. We show that BOULE is recruited to the SGs upon heat stress, and that these SGs are developmental stage-specific. These results suggest that DAZ family proteins may have conserved roles in the SGs of male germ cells.

Algae-bacteria interactions: Evolution, ecology and emerging applications.

Algae and bacteria have coexisted ever since the early stages of evolution. This coevolution has revolutionized life on earth in many aspects. Algae and bacteria together influence ecosystems as varied as deep seas to lichens and represent all conceivable modes of interactions - from mutualism to parasitism. Several studies have shown that algae and bacteria synergistically affect each other's physiology and metabolism, a classic case being algae-roseobacter interaction. These interactions are ubiquitous and define the primary productivity in most ecosystems. In recent years, algae have received much attention for industrial exploitation but their interaction with bacteria is often considered a contamination during commercialization. A few recent studies have shown that bacteria not only enhance algal growth but also help in flocculation, both essential processes in algal biotechnology. Hence, there is a need to understand these interactions from an evolutionary and ecological standpoint, and integrate this understanding for industrial use. Here we reflect on the diversity of such relationships and their associated mechanisms, as well as the habitats that they mutually influence. This review also outlines the role of these interactions in key evolutionary events such as endosymbiosis, besides their ecological role in biogeochemical cycles. Finally, we focus on extending such studies on algal-bacterial interactions to various environmental and bio-technological applications.

Ni/MgO-MgAl2O4 Catalysts with Bimodal Pore Structure for Steam-CO2-Reforming of Methane.

The bead type MgO-MgAl2O4 catalyst supports with bimodal pore structures were fabricated via an extrusion molding of gels derived from the precursor mixture of mesoporous MgO particles and aluminum magnesium hydroxide, followed by heat treatment. To investigate the effect of macro pore structures on the catalytic activity of the Ni/MgO-MgAl2O4 catalysts in the steam and carbon dioxide reforming of methane (SCR), two kinds of the catalysts with largely different macro pore volumes and sizes but nearly the same meso pore volume and size were compared. The bimodal catalyst with a large macro pore size and volume exhibited a highly enhanced CO2 conversion from 22.3 to 37.1% but a slightly reduced CH4 conversion from 95.3 to 92.1% at the same feed ratio. The SCR results show that the large macro pores can lead to a highly enhanced mass transfer rate of CO2 absorption into the pore channels of the magnesium alumina spinel.

Polypropylene Bundle Attached Multilayered Stigeoclonium Biofilms Cultivated in Untreated Sewage Generate High Biomass and Lipid Productivity.

The potential of microalgae biofuel has not been realized because of the low productivity and high costs associated with the current cultivation systems. In this study, a new low-cost and transparent attachment material was tested for cultivation of a filamentous algal strain, Stigeoclonium sp., isolated from wastewater. Initially, the different materials tested for Stigeoclonium cultivation in untreated wastewater were nylon mesh, polyethylene mesh, polypropylene bundle (PB), polycarbonate plate, and viscose rayon. Among the materials tested, PB led to a firm attachment, high biomass (53.22 g/m(2), dry cell weight), and total lipid yield (5.8 g/m(2)) with no perceivable change in FAME profile. The Stigeoclonium-dominated biofilm consisted of bacteria and extracellular polysaccharide, which helped in biofilm formation and for effective wastewater treatment (viz., removal efficiency of total nitrogen and total phosphorus corresponded to ~38% and ~90%, respectively). PB also demonstrated high yields under multilayered cultivation in a single reactor treating wastewater. Hence, this system has several advantages over traditional suspended and attached systems, with possibility of increasing areal productivity three times using Stigeoclonium sp. Therefore, multilayered attached growth algal cultivation systems seem to be the future cultivation model for large-scale biodiesel production and wastewater treatment.

Organic carbon, influent microbial diversity and temperature strongly influence algal diversity and biomass in raceway ponds treating raw municipal wastewater.

Algae based wastewater treatment coupled to biofuel production has financial benefits and practical difficulties. This study evaluated the factors influencing diversity and growth of indigenous algal consortium cultivated on untreated municipal wastewater in a high rate algal pond (HRAP) for a period of 1 year using multivariate statistics. Diversity analyses revealed the presence of Chlorophyta, Cyanophyta and Bacillariophyta. Dominant microalgal genera by biovolume in various seasons were Scenedesmus sp., Microcystis sp., and Chlorella sp. Scenedesmus sp., persisted throughout the year but none of three strains co-dominated with the other. The most significant factors affecting genus dominance were temperature, inflow cyanophyta and organic carbon concentration. Cyanophyta concentration affected microalgal biomass and diversity, whereas temperature impacted biomass. Preferred diversity of microalgae is not sustained in wastewater systems but is obligatory for biofuel production. This study serves as a guideline to sustain desired microalgal consortium in wastewater treatment plants for biofuel production.

Enhancing microalgal biomass productivity by engineering a microalgal-bacterial community.

This study demonstrates that ecologically engineered bacterial consortium could enhance microalgal biomass and lipid productivities through carbon exchange. Phycosphere bacterial diversity analysis in xenic Chlorella vulgaris (XCV) confirmed the presence of growth enhancing and inhibiting microorganisms. Co-cultivation of axenic C. vulgaris (ACV) with four different growth enhancing bacteria revealed a symbiotic relationship with each bacterium. An artificial microalgal-bacterial consortium (AMBC) constituting these four bacteria and ACV showed that the bacterial consortium exerted a statistically significant (P<0.05) growth enhancement on ACV. Moreover, AMBC had superior flocculation efficiency, lipid content and quality. Studies on carbon exchange revealed that bacteria in AMBC might utilize fixed organic carbon released by microalgae, and in return, supply inorganic and low molecular weight (LMW) organic carbon influencing algal growth and metabolism. Such exchanges, although species specific, have enormous significance in carbon cycle and can be exploitated by microalgal biotechnology industry.

A cost analysis of microalgal biomass and biodiesel production in open raceways treating municipal wastewater and under optimum light wavelength.

Open raceway ponds are cost-efficient for mass cultivation of microalgae compared with photobioreactors. Although low-cost options like wastewater as nutrient source is studied to overcome the commercialization threshold for biodiesel production from microalgae, a cost analysis on the use of wastewater and other incremental increases in productivity has not been elucidated. We determined the effect of using wastewater and wavelength filters on microalgal productivity. Experimental results were then fitted into a model, and cost analysis was performed in comparison with control raceways. Three different microalgal strains, Chlorella vulgaris AG10032, Chlorella sp. JK2, and Scenedesmus sp. JK10, were tested for nutrient removal under different light wavelengths (blue, green, red, and white) using filters in batch cultivation. Blue wavelength showed an average of 27% higher nutrient removal and at least 42% higher chemical oxygen demand removal compared with white light. Naturally, the specific growth rate of microalgae cultivated under blue wavelength was on average 10.8% higher than white wavelength. Similarly, lipid productivity was highest in blue wavelength, at least 46.8% higher than white wavelength, whereas FAME composition revealed a mild increase in oleic and palmitic acid levels. Cost analysis reveals that raceways treating wastewater and using monochromatic wavelength would decrease costs from 2.71 to 0.73 $/kg biomass. We prove that increasing both biomass and lipid productivity is possible through cost-effective approaches, thereby accelerating the commercialization of low-value products from microalgae, like biodiesel.