Yates JA et al. (1985) Am J Trop Med Hyg "Brugia malayi: vaccination of jirds with 60cobalt-attenuated infective stage larvae protects against homologous challenge."

Yates JA, Higashi GI

[Am J Trop Med Hyg, 1985]

Vaccination of inbred jirds (Meriones unguiculatus) with 60cobalt radiation-attenuated Brugia malayi infective stage larvae (L3) protected against homologous challenge given either subcutaneously (sc) or by the intraperitoneal (ip) route. Groups of jirds vaccinated once sc with 75, 15 Krad L3 showed from 69% to 91% reduction in recovered worms after ip challenge infection compared to infection in non-vaccinated control jirds, while 75% reduction in mean worm burden was seen in jirds receiving sc challenge infection. A single sc vaccination with 75, 10 or 20 Krad L3 produced no protection (10 Krad) and 64% reduction in recovered worms (20 Krad). Therefore the 15 Krad dose appeared to be best. A marked increase in anti-B. malayi antibody in vaccinated jirds was seen (by ELISA) immediately after challenge infection and an immunofluorescence assay showed that L3 incubated in serum from vaccinated jirds were completely and uniformly covered with specific antibody. Eosinophil-rich granulomas containing dead and moribund L3 were recovered from vaccinated jirds. This model of protective immunity in a Brugia-susceptible small rodent may provide a useful system for identification of molecularly defined filarial-protective immunogens.

Alanis-Lobato G et al. (2013) Genomics "Exploitation of genetic interaction network topology for the prediction of epistatic behavior."

Ravasi T, Cannistraci CV, Alanis-Lobato G

[Genomics, 2013]

Genetic interaction (GI) detection impacts the understanding of human disease and the ability to design personalized treatment. The mapping of every GI in most organisms is far from complete due to the combinatorial amount of gene deletions and knockdowns required. Computational techniques to predict new interactions based only on network topology have been developed in network science but never applied to GI networks. We show that topological prediction of GIs is possible with high precision and propose a graph dissimilarity index that is able to provide robust prediction in both dense and sparse networks. Computational prediction of GIs is a strong tool to aid high-throughput GI determination. The dissimilarity index we propose in this article is able to attain precise predictions that reduce the universe of candidate GIs to test in the lab.

Boucher B et al. (2016) PLoS Comput Biol "Structural and Functional Characterization of a Caenorhabditis elegans Genetic Interaction Network within Pathways."

Hallett M, Boucher B, Jenna S, Lee AY

[PLoS Comput Biol, 2016]

A genetic interaction (GI) is defined when the mutation of one gene modifies the phenotypic expression associated with the mutation of a second gene. Genome-wide efforts to map GIs in yeast revealed structural and functional properties of a GI network. This provided insights into the mechanisms underlying the robustness of yeast to genetic and environmental insults, and also into the link existing between genotype and phenotype. While a significant conservation of GIs and GI network structure has been reported between distant yeast species, such a conservation is not clear between unicellular and multicellular organisms. Structural and functional characterization of a GI network in these latter organisms is consequently of high interest. In this study, we present an in-depth characterization of ~1.5K GIs in the nematode Caenorhabditis elegans. We identify and characterize six distinct classes of GIs by examining a wide-range of structural and functional properties of genes and network, including co-expression, phenotypical manifestations, relationship with protein-protein interaction dense subnetworks (PDS) and pathways, molecular and biological functions, gene essentiality and pleiotropy. Our study shows that GI classes link genes within pathways and display distinctive properties, specifically towards PDS. It suggests a model in which pathways are composed of PDS-centric and PDS-independent GIs coordinating molecular machines through two specific classes of GIs involving pleiotropic and non-pleiotropic connectors. Our study provides the first in-depth characterization of a GI network within pathways of a multicellular organism. It also suggests a model to understand better how GIs control system robustness and evolution.

Zheng X et al. (2015) Nanoscale "Silica-coated bismuth sulfide nanorods as multimodal contrast agents for a non-invasive visualization of the gastrointestinal tract."

Gao B, Gu Z, Shi J, Tian G, Hu Z, Zhao Y, Liu X, Yang Z, Yan L, Zhang X, Zheng X, Yin W, Bu Y

[Nanoscale, 2015]

Non-invasive and real-time imaging of the gastrointestinal (GI) tract is particularly desirable for research and clinical studies of patients with symptoms arising from gastrointestinal diseases. Here, we designed and fabricated silica-coated bismuth sulfide nanorods (Bi2S3@SiO2 NRs) for a non-invasive spatial-temporally imaging of the GI tract. The Bi2S3 NRs were synthesized by a facile solvothermal method and then coated with a SiO2 layer to improve their biocompatibility and stability in the harsh environments of the GI tract, such as the stomach and the small intestine. Due to their strong X-ray- and near infrared-absorption abilities, we demonstrate that, following oral administration in mice, the Bi2S3@SiO2 NRs can be used as a dual-modal contrast agent for the real-time and non-invasive visualization of NRs distribution and the GI tract via both X-ray computed tomography (CT) and photoacoustic tomography (PAT) techniques. Importantly, integration of PAT with CT provides complementary information on anatomical details with high spatial resolution. In addition, we use Caenorhabditis Elegans (C. Elegans) as a simple model organism to investigate the biological response of Bi2S3@SiO2 NRs by oral administration. The results indicate that these NRs can pass through the GI tract of C. Elegans without inducing notable toxicological effects. The above results suggest that Bi2S3@SiO2 NRs pave an alternative way for the fabrication of multi-modal contrast agents which integrate CT and PAT modalities for a direct and non-invasive visualization of the GI tract with low toxicity.

Yates JA et al. (1985) Acta Trop "Activation of the alternative complement pathway in normal human serum by Loa loa and Brugia malayi infective stage larvae."

Yates JA, Eberhard ML, Lowrie RC, Lowichik A, Orihel TC, Higashi GI

[Acta Trop, 1985]

Infective stage larvae (L3) of Loa loa and Brugia malayi upon in vitro incubation with normal human serum activated the alternative complement pathway. C3 conversion products were detected on larval cuticles by eosinophil adherence and by immunofluorescence with C3c antiserum. No evidence for cuticle binding of IgG, IgA, IgM, Clq, or C4 was found by immunofluorescence. L3-induced C3 activation was inhibited by 10 mM EDTA but unaffected by 10 mM Mg++-EGTA. Human sera deficient in C2, C4, or C6 incubated with L3 resulted in C3 activation. However, sera treated with zymosan or heated for 1 h, 56 degrees C were unreactive with L3. Immunoelectrophoresis of fresh serum exposed to L3 for 1 h at 37 degrees C showed C3 cleavage products. The results indicate that these nematode L3 activate the alternative complement cascade via cuticular surface components. Larval viability was unaffected by complement activation or by adherence of eosinophils.

Chen D et al. (2019) Cell Rep "Revealing Functional Crosstalk between Distinct Bioprocesses through Reciprocal Functional Tests of Genetically Interacting Genes."

Xu W, Chen J, Xia T, Dong Y, Yang Z, Gao J, Zhou J, Myers CL, Wei J, Ye Y, Shi A, Cheng W, Wang S, Yu M, Grant BD, Wang Y, Zhang H, Fu X, Chen D, Ma K, Wang H

[Cell Rep, 2019]

To systematically explore the genes mediating functional crosstalk between metazoan biological processes, we apply comparative genetic interaction (GI) mapping in Saccharomyces cerevisiae and Caenorhabditis elegans to generate an inter-bioprocess network consisting of 178 C.elegans GIs. The GI network spans six annotated biological processes including aging, intracellular transport, microtubule-based processes, cytokinesis, lipid metabolic processes, and anatomical structure development. By proposing a strategy called "reciprocal functional test" for interacting gene pairs, we discover a group of genes that mediate crosstalk between distinct biological processes. In particular, we identify the ribosomal S6 Kinase/RSKS-1, previously characterized as an mTOR (mechanistic target of rapamycin) effector, as a regulator of DAF-2 endosomal recycling transport, which traces a functional correlation between endocytic recycling and aging processes. Together, our results provide an alternative and effective strategy for identifying genes and pathways that mediate crosstalk between bioprocesses with little prior knowledge.

Keloth T et al. (2019) Diagn Cytopathol "Microfilaria and Strongyloides larva diagnosed in cerebrospinal fluid and ascitic fluid, respectively: Approach to their morphology on cytology."

Toi PC, Keloth T, Gochhait D, Rajkumari N, Gudivada V, Siddaraju N

[Diagn Cytopathol, 2019]

Filariasis and Strongyloidiasis are two endemic parasitic infections seen in any tropical country. Filariasis, commonly caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori is seen often in peripheral blood and lymphoid tissue. But it can be isolated from wide variety of soft tissue sites in the body like soft tissue lumps, breast, thyroid, body fluids. Strongyloides stercoralis, a helminthic infection, usually affects the respiratory and gastrointestinal (GI) tract, and frequently picked up in GI biopsies. However, in cases of hyper infection and patients with altered immunity, it can be isolated from other rare sites like body fluid samples. Accurate morphological Identification and confirmation are important for specific management. We report a case of microfilaria isolated from cerebrospinal fluid and a case of Strongyloides larva isolated from ascitic fluid in clinically unsuspected cases of these two parasitic infestations. We have also added a brief discussion on morphological differences between the two larval forms.

Sheng L et al. (2012) Microb Biotechnol "Interkingdom adenosine signal reduces Pseudomonas aeruginosa pathogenicity."

Zhang Y, Jayaraman A, Hegde M, Sheng L, Wood TK, Pu M

[Microb Biotechnol, 2012]

Pseudomonas aeruginosa is becoming recognized as an important pathogen in the gastrointestinal (GI) tract. Here we demonstrate that adenosine, derived from hydrolysis of ATP from the eucaryotic host, is a potent interkingdom signal in the GI tract for this pathogen. The addition of adenosine nearly abolished P.aeruginosa biofilm formation and abolished swarming by preventing production of rhamnolipids. Since the adenosine metabolite inosine did not affect biofilm formation and since a mutant unable to metabolize adenosine behaved like the wild-type strain, adenosine metabolism is not required to reduce pathogenicity. Adenosine also reduces production of the virulence factors pyocyanin, elastase, extracellular polysaccharide, siderophores and the Pseudomonas quinolone signal which led to reduced virulence with Caenorhabditis elegans. To provide insights into how adenosine reduces the virulence of P.aeruginosa, a whole-transcriptome analysis was conducted which revealed that adenosine addition represses genes similar to an iron-replete condition; however, adenosine did not directly bind Fur. Therefore, adenosine decreases P.aeruginosa pathogenicity as an interkingdom signal by causing genes related to iron acquisition to be repressed.

Liro MJ et al. (2016) Genetics "Mitotic Spindle Positioning in the EMS Cell of Caenorhabditis elegans Requires LET-99 and LIN-5/NuMA."

Rose LS, Liro MJ

[Genetics, 2016]

Asymmetric divisions produce daughter cells with different fates, and thus are critical for animal development. During asymmetric divisions, the mitotic spindle must be positioned on a polarized axis to ensure the differential segregation of cell fate determinants into the daughter cells. In many cell types a cortically localized complex consisting of G, GPR-1/2, and LIN-5 (Gi/Pins/Mud, Gi/LGN/NuMA) mediates the recruitment of dynactin/dynein, which exerts pulling forces on astral microtubules to physically position the spindle. The conserved PAR polarity proteins are known to regulate both cytoplasmic asymmetry and spindle positioning in many cases. However, spindle positioning also occurs in response to cell signaling cues that appear to be PAR-independent. In the four-cell Caenorhabditis elegans embryo, Wnt and Mes-1/Src-1 signaling pathways act partially redundantly to align the spindle on the anterior/posterior axis of the EMS cell. It is unclear how those extrinsic signals individually contribute to spindle positioning and whether either pathway acts via conserved spindle-positioning regulators. Here, we genetically test the involvement of G, LIN-5, and their negative regulator LET-99, in transducing EMS spindle positioning polarity cues. We also examined whether the C. elegans ortholog of another spindle positioning regulator, DLG-1, is required. We show that LET-99 acts in the Mes-1/Src-1 pathway for spindle positioning. LIN-5 is also required for EMS spindle positioning, possibly through a G and DLG-1 independent mechanism.

Fu J et al. (2018) Biophys Rep "AIM interneurons mediate feeding suppression through the TYRA-2 receptor inC. elegans."

Huang W, Song E, Zhang H, Sheng Y, Zhu X, Xu T, Fu J

[Biophys Rep, 2018]

Feeding behavior is the most fundamental behavior in<i>C. elegans</i>. Our previous results have dissected the central integration circuit for the regulation of feeding, which integrates opposing sensory inputs and regulates feeding behavior in a nonlinear manner. However, the peripheral integration that acts downstream of the central integration circuit to modulate feeding remains largely unknown. Here, we find that a Gi/o-coupled tyramine receptor, TYRA-2, is involved in peripheral feeding suppression. TYRA-2 suppresses feeding behavior via the AIM interneurons, which receive tyramine/octopamine signals from RIM/RIC neurons in the central integration circuit. Our results reveal previously unidentified roles for the receptor TYRA-2 and the AIM interneurons in feeding regulation, providing a further understanding of how biogenic amines tyramine and octopamine regulate feeding behavior.