Amphid sensory neurons of Caenorhabditis elegans orchestrate its survival from infection with broad classes of pathogens

The survival of a host during infection relies on its ability to rapidly sense the invading pathogen and mount an appropriate response. The bacterivorous nematode Caenorhabditis elegans lacks most of the traditional pattern recognition mechanisms. In this study, we hypothesized that the 12 pairs of amphid sensory neurons in the heads of worms provide sensing capability and thus affect survival during infection. We tested animals lacking amphid neurons to three major classes of pathogens, namely—a Gram-negative bacterium Pseudomonas aeruginosa, a Gram-positive bacterium Enterococcus faecalis, and a pathogenic yeast Cryptococcus neoformans. By using individual neuronal ablation lines or mutants lacking specific neurons, we demonstrate that some neurons broadly suppress the survival of the host and colonization of all pathogens, whereas other amphid neurons differentially regulate host survival during infection. We also show that the roles of some of these neurons are pathogen-specific, as seen with the AWB odor sensory neurons that promote survival only during infections with P. aeruginosa. Overall, our study reveals broad and specific roles for amphid neurons during infections.</p

Homeostatic control of stearoyl desaturase expression via patched-like receptor PTR-23 ensures the survival of C. elegans during heat stress

Organismal responses to temperature fluctuations include an evolutionarily conserved cytosolic chaperone machinery as well as adaptive alterations in lipid constituents of cellular membranes. Using C. elegans as a model system, we asked whether adaptable lipid homeostasis is required for survival during physiologically relevant heat stress. By systematic analyses of lipid composition in worms during and before heat stress, we found that unsaturated fatty acids are reduced in heat-stressed animals. This is accompanied by the transcriptional downregulation of fatty acid desaturase enzymes encoded by fat-1, fat-3, fat-4, fat-5, fat-6, and fat-7 genes. Conversely, overexpression of the Δ9 desaturase FAT-7, responsible for the synthesis of PUFA precursor oleic acid, and supplementation of oleic acid causes accelerated death of worms during heat stress. Interestingly, heat stress causes permeability defects in the worm’s cuticle. We show that fat-7 expression is reduced in the permeability defective collagen (PDC) mutant, dpy-10, known to have enhanced heat stress resistance (HSR). Further, we show that the HSR of dpy-10 animals is dependent on the upregulation of PTR-23, a patched-like receptor in the epidermis, and that PTR-23 downregulates the expression of fat-7. Consequently, abrogation of ptr-23 in wild type animals affects its survival during heat stress. This study provides evidence for the negative regulation of fatty acid desaturase expression in the soma of C. elegans via the non-canonical role of a patched receptor signaling component. Taken together, this constitutes a skin-gut axis for the regulation of lipid desaturation to promote the survival of worms during heat stress.<br/

Water Filtration Using Plant Xylem

Effective point-of-use devices for providing safe drinking water are urgently needed to reduce the global burden of waterborne disease. Here we show that plant xylem from the sapwood of coniferous trees – a readily available, inexpensive, biodegradable, and disposable material – can remove bacteria from water by simple pressure-driven filtration. Approximately 3 cm3 of sapwood can filter water at the rate of several liters per day, sufficient to meet the clean drinking water needs of one person. The results demonstrate the potential of plant xylem to address the need for pathogen-free drinking water in developing countries and resource-limited settings

Trend Analysis of Modern Cyber Attacks with the Adoption of the Cloud

Since its initial growth in the late 1990s, Cloud technology has gained widespread traction as the future of IT Modernization. Cloud services utilize the internet rather than a local device to regulate services and programs. External vendors maintain these online servers and software platforms in return for a cost. A noteworthy phenomenon with the rising popularity and use of Cloud-based platforms is the parallel surge of modern-day data attacks. As an evolving and widely-used technology, my research explains whether (if) Cloud Adoption (adopting to Cloud technology) contributes to an increase in digital vulnerabilities and attacks. Upon reviewing the development and evolution of the Cloud, weaknesses and security consequences of Cloud Systems, and case studies of Cloud Adoption, a general trend suggests that malicious online players take advantage of low user knowledge of utilizing and securing Cloud systems to facilitate attacks. A significant portion of security breaches on online platforms originates from user error rather than service error. Overall, this specific line of technological inquiry was selected given the rise of modern-day cybercrime. With the growth of the online domain, my research underscores the relationship between cyber-crime and the advancement of the internet and cutting-edge technological developments

DESIGNING mRNA BASED MULTISTAGE VACCINE FOR MALARIA

Malaria continues to be a life-threatening disease severely affecting pregnant women and children below 5 years with a mortality rate of 12 deaths per 1000 individuals per year. P.falciparum malaria accounts for 94% of cases that occur in sub-Saharan Africa. Multiple eradication campaigns have been implemented, including vector control, chemotherapy, and chemoprophylaxis. Effective implementation of this strategy is still a challenge. RTS, S, the first WHO approved malaria vaccine, has ~40% efficacy in the first year and less than ~30% in the subsequent years. This vaccine targets the liver stage of the parasite and does not target the disease-causing form of the parasite. Clinical disease is caused by the asexual form of the parasite that replicates in the red blood cells (RBCs). Hence, a vaccine targeting both the liver stages and the blood stage of the parasite could be an approach used to prevent infection and disease. The merozoites invade RBCs by secreting their own receptor, the RON complex, onto the plasma membrane of the red blood cells. A small, conserved region of the RON2 protein (RON2L, a 49 amino acid region of RON2) binds to the AMA1 and enables the commitment of the parasite to invasion. Previous studies performed in Aotus monkeys show that vaccination with a pre-formed AMA1-RON2L complex in Freund’s adjuvant protects against virulent Plasmodium falciparum infection. Similar studies performed in mice have also shown complete protection in mice against P. yoelii. (Srinivasan et.al. 2014 and 2017). Presuming that the immune system would recognize this complex, we developed AMA1-RON2L fusion protein mRNA construct that would generate better invasion inhibitory antibodies than AMA1 alone. Two different constructs of the AMA1-RON2L fusion protein by targeting the protein to the cell membrane or to be extracellularly secreted were generated. These were designed to test the impact of the form of the antigen (transmembrane and secretory) on immunogenicity. In addition to the blood stage targeting vaccines, we also generated two mRNA vaccines that target the liver stage of the parasite. In this case we tested if immature dendritic cell (iDC) targeting by fusion of CSP with the MIP3α chemokine(Macrophage inflammatory protein 3alpha , also designated (C-C motif ligand 20 CCL20) will enhance immunogenicity compared to CSP-alone. Our aim was to analyze these vaccines separately with a goal of subsequently combining these antigenic targets with the best immunogen (eg., membrane anchored or secreted iDC-targeting antigen) to develop a multistage malaria vaccine. Our results suggest that the membrane anchoring of AMA1-RON2L fusion antigen induces higher antibody titers in comparison to the secretory construct. Interestingly, adding the MIP3α chemokine tag to the CSP mRNA construct enhanced the antibody titers against the NANP repeat and conferred significantly greater protection against sporozoite challenge. Our results suggest that membrane anchoring the immunogen expressed by nucleic acid vaccines may enhance immunogenicity and iDC targeting can further promote vaccine responses. Combining CSP and AMA-targeting vaccines together can help build a multistage vaccine to prevent both infection and disease

G protein-coupled receptors: The choreographers of innate immunity in Caenorhabditis elegans.

Caenorhabditis elegans is a free-living, bacterivorous nematode that frequently encounterspathogens while foraging for food in decomposing vegetation. Like other invertebrates, C. elegans entirely relies on its innate immune system to combat invading pathogens. A basal flightor fight response of animals is also observed in worms against infection. The former is an aversion response of C. elegans against select pathogens, and the latter is an inducible innateresponse comprising of pathogen-specific effectors including lysozymes, lectins, antimicrobialpeptides (AMPs), and cytoprotective molecules. Although pathogen recognition in worms ispoorly understood, various signaling pathways and immune effectors facilitating defenseresponse are well studied, making this nematode an excellent model to study host–microbeinteractions. In higher vertebrates such as mice and humans, sensing of infection throughpathogen-associated molecular patterns (PAMPs) or host damage-associated molecular patterns (DAMPs) is primarily mediated by the toll-like receptors (TLRs), nod-like receptors(NLRs), RIG-I like receptors (RLRs), C-type lectin domain (CTLD) proteins, and AIM-likereceptors (ALRs) [1]. Humans have 10 TLRs that sense PAMPs and DAMPs. However, TOL1, the only TLR homolog in C. elegans, does not seem to be essential during infections withmost pathogens, except during Salmonella enterica [2] and Serratia marcescens [3] infections.The C. elegans RIG-I like receptor DRH-1 detects products of viral replication and activates anintracellular pathogen response [4]. CLEC-39 and CLEC-49, two CTLD proteins in C. elegans,are essential for immune responses against S. marcescens and are known to bind live bacteria[5]. Despite all these findings, the molecular mechanisms involved in pattern recognition by C.elegans during a majority of infections remain elusive. In this review, we examine the roles ofG protein-coupled receptors (GPCRs) as noncanonical pattern recognition receptors (PRRs)and also discuss how GPCR signaling in C. elegans regulates various immune processes.GPCRs form the largest superfamily of cell surface receptors in eukaryotes; C. elegansencodes approximately 1,300 genes encoding putative GPCRs [6]. They are involved in a variety of physiological processes [7] and also for detecting various environmental cues, includingbacterial secondary metabolites [8]. In recent years, several studies on infection in C. eleganshave revealed the importance of GPCRs and their signaling in host defense. In this review, weexamine the role of GPCRs in innate immunity via the modulation of “flight” or “fight”responses of C. elegans

The Trick is to Live: Is the Estate Tax Social Security for the Rich?

Because estate tax liability usually depends on how long one lives, it implicitly provides annuity income. In the absence of annuity markets, lump-sum estate taxation may be used to achieve the first-best solution for individuals with a sufficiently strong bequest motive. Calculations of the annuity embedded in the U.S. estate tax show that people with $10 million of assets may be effectively receiving more than$100,000 a year financed at actuarially fair rates by their tax payments. According to my calibrations, the insurance effect reduces the marginal cost of funds (MCF) for the estate tax by as much as 30 % and the resulting MCF is within the range of estimates for the marginal cost of funds for the income tax

Filtration performance of the xylem filter.

<p>a) Feed solution of a pigment dye before filtration (left), compared to the filtrate (right). b) Size distribution of the pigment particles in the feed and filtrate solutions measured by dynamic light scattering. c) Dependence of the rejection on the particle size estimated from the data in (b). d) Cross-section of the xylem filter after filtration. Scale is in centimeters and inches.</p

Xylem filter.

<p>a) Construction of xylem filter. b) Effect of applied pressure on the water flux through the xylem filter. c) Hydrodynamic conductivity of the filter extracted at each measured pressure using the total filter cross-section area and thickness as defined by <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0089934#pone.0089934.e001" target="_blank">Equation 1</a>. Error bars indicate ±S.D. for measurements on three different xylem filters.</p