Inhibition of the UFD-1-NPL-4 complex triggers an aberrant immune response in .

The UFD-1 (ubiquitin fusion degradation 1)-NPL-4 (nuclear protein localization homolog 4) heterodimer is involved in extracting ubiquitinated proteins from several plasma membrane locations, including the endoplasmic reticulum. This heterodimer complex helps in the degradation of ubiquitinated proteins via the proteasome with the help of the AAA+ ATPase CDC-48. While the ubiquitin-proteasome system is known to have important roles in maintaining innate immune responses, the role of the UFD-1-NPL-4 complex in regulating immunity remains elusive.

Innate immune and endoplasmic reticulum unfolded protein response pathways protect against chloroquine toxicity.

Chloroquine (CQ) is a 4-aminoquinoline that has historically been used as an anti-malarial drug. It has also been used to treat several autoimmune diseases, cancers, and viral infections. Most of the effects of CQ are mediated through its ability to accumulate in acidic vacuoles and increase their pH.

Redox imbalance and hypoxia-inducible factors: a multifaceted crosstalk.

Redox homeostasis, the delicate balance between oxidative and reductive processes, is crucial for cellular function and overall organismal health. At the molecular level, cells need to maintain a fine balance between the levels of reactive oxygen species (ROS) and reducing equivalents such as glutathione and nicotinamide adenine dinucleotide phosphate. The perturbation of redox homeostasis due to excessive ROS production leads to oxidative stress that can damage lipids, proteins, and nucleic acids.

Calcineurin inhibition enhances lifespan by defecation defects-mediated calorie restriction and nuclear hormone signaling.

Calcineurin is a highly conserved calcium/calmodulin-dependent serine/threonine protein phosphatase with diverse functions. Inhibition of calcineurin is known to enhance the lifespan of through multiple signaling pathways. Aiming to study the role of calcineurin in regulating innate immunity, we discover that calcineurin is required for the rhythmic defecation motor program (DMP) in .

Polyoxometalate-HKUST-1 composite derived nanostructured Na-Cu-MoC catalyst for efficient reverse water gas shift reaction.

Transforming CO to CO reverse water-gas shift (RWGS) reaction is widely regarded as a promising technique for improving the efficiency and economics of CO utilization processes. Moreover, it is also considered as a pathway towards e-fuels. Cu-oxide catalysts are widely explored for low-temperature RWGS reactions; nevertheless, they tend to deactivate significantly under applied reaction conditions due to the agglomeration of copper particles at elevated temperatures.

Thiol reductive stress activates the hypoxia response pathway.

Owing to their capability to disrupt the oxidative protein folding environment in the endoplasmic reticulum (ER), thiol antioxidants, such as dithiothreitol (DTT), are used as ER-specific stressors. We recently showed that thiol antioxidants modulate the methionine-homocysteine cycle by upregulating an S-adenosylmethionine-dependent methyltransferase, rips-1, in Caenorhabditis elegans. However, the changes in cellular physiology induced by thiol stress that modulate the methionine-homocysteine cycle remain uncharacterized.

Process intensification for sustainable extraction of metals from e-waste: challenges and opportunities.

The electrical and electronic waste is expected to increase up to 74.7 million metric tons by 2030 due to the unparalleled replacement rate of electronic devices, depleting the conventional sources of valuable metals such as rare earth elements, platinum group metals, Co, Sb, Mo, Li, Ni, Cu, Ag, Sn, Au, and Cr. Most of the current techniques for recycling, recovering, and disposing of e-waste are inappropriate and therefore contaminate the land, air, and water due to the release of hazardous compounds into the environment.

Optimization of 'on farm' hydropriming conditions in wheat: Soaking time and water volume have interactive effects on seed performance.

Seed priming is a simple and cost effective method to obtain a better plant stand under diverse environmental conditions. The current study was designed to determine the optimal priming duration and water volume for wheat seed. For this experiment, three wheat genotypes with distinct genetic and adaptive backgrounds were chosen.

ERASing endoplasmic reticulum stress: the faster, the better.

The endoplasmic reticulum (ER) has evolved multiple mechanisms to maintain homeostasis under stress conditions. A recent study by Efstathiou et al. identified a novel mechanism of silencing ER-associated RNAs by the exogenous RNA interference pathway.

α-Terpineol synergizes with gentamicin to rescue Caenorhabditis elegans from Pseudomonas aeruginosa infection by attenuating quorum sensing-regulated virulence.

Aims: This study scrutinized α-Terpineol (α-T) for its anti-virulence and anti-fouling potential against P. aeruginosa PAO1 in conjunction with gentamicin (GeN) using in-vitro, in-silico, and in-vivo approaches.

Main Methods: The quorum quenching (QQ) potential of the drug combination was studied using a quorum sensing (QS) biosensor strain and tested for synergy using chequerboard and time-kill kinetics assays.

Gentamicin Augments the Quorum Quenching Potential of Cinnamaldehyde and Protects From Infection.

The quorum sensing (QS) circuitry of represents an attractive target to attenuate bacterial virulence and antibiotic resistance. In this context, phytochemicals harboring anti-virulent properties have emerged as an alternative medicine to combat pseudomonal infections. Hence, this study was undertaken to investigate the synergistic effects and quorum quenching (QQ) potential of cinnamaldehyde (CiNN) in combination with gentamicin (GeN) against .

Dithiothreitol causes toxicity in by modulating the methionine-homocysteine cycle.

The redox reagent dithiothreitol (DTT) causes stress in the endoplasmic reticulum (ER) by disrupting its oxidative protein folding environment, which results in the accumulation and misfolding of the newly synthesized proteins. DTT may potentially impact cellular physiology by ER-independent mechanisms; however, such mechanisms remain poorly characterized. Using the nematode model , here we show that DTT toxicity is modulated by the bacterial diet.

Bacterial Lawn Avoidance and Bacterial Two Choice Preference Assays in .

Physical avoidance of pathogens is a crucial defense strategy used by the host to reduce pathogen infection. Hosts display the use of multiple strategies to sense and avoid pathogens, ranging from olfaction to sensing of damage caused by pathogen infection. Understanding various mechanisms of pathogen avoidance has the potential to uncover conserved host defense responses that are important against pathogen infections.

Extracellular Proteostasis: Laying Siege to Pathogens.

How protein homeostasis is maintained in the extracellular space remains poorly studied. A recent study employed a Caenorhabditis elegans model to carry out a systematic analysis of the extracellular proteostasis network and uncovered its role in combating a pathogenic attack.

Harnessing the power of genetics: fast forward genetics in Caenorhabditis elegans.

Forward genetics is a powerful tool to unravel molecular mechanisms of diverse biological processes. The success of genetic screens primarily relies on the ease of genetic manipulation of an organism and the availability of a plethora of genetic tools. The roundworm Caenorhabditis elegans has been one of the favorite models for genetic studies due to its hermaphroditic lifestyle, ease of maintenance, and availability of various genetic manipulation tools.

Phase Separation of RNA Helicase Triggers Stress-Responsive Translational Switch.

A swift response to stress requires global translational suppression, excepting stress proteins. Recently, Iserman et al. uncovered that stress-induced phase separation of the RNA helicase Ded1p results in translational suppression of housekeeping transcripts that contain complex 5' untranslated regions (UTRs).

Neural control of behavioral and molecular defenses in C. elegans.

The nervous and immune systems use bi-directional communication to control host responses against microbial pathogens. Recent studies at the interface of the two systems have highlighted important roles of the nervous system in the regulation of both microbicidal pathways and pathogen avoidance behaviors. Studies on the neural circuits in the simple model host Caenorhabditis elegans have significantly improved our understanding of the roles of conserved neural mechanisms in controlling innate immunity.

Intestinal infection regulates behavior and learning via neuroendocrine signaling.

The recognition of pathogens and subsequent activation of defense responses are critical for the survival of organisms. The nematode recognizes pathogenic bacteria and elicits defense responses by activating immune pathways and pathogen avoidance. Here we show that chemosensation of phenazines produced by pathogenic , which leads to rapid activation of DAF-7/TGF-β in ASJ neurons, is insufficient for the elicitation of pathogen avoidance behavior.

Similar Neural Pathways Control Foraging in Mosquitoes and Worms.

Female mosquitoes bite human hosts to obtain a blood meal and, in the process, act as vectors for many disease-causing viruses, including the dengue, chikungunya, yellow fever, and Zika viruses. After a complete meal, the female mosquitoes lose attraction to their hosts for several days. New research shows that pharmacological activation of neuropeptide Y-like receptor (NPYLR) signaling elicits host aversion in female mosquitoes.

Microbial Colonization Activates an Immune Fight-and-Flight Response via Neuroendocrine Signaling.

The ability to distinguish harmful and beneficial microbes is critical for the survival of an organism. Here, we show that bloating of the intestinal lumen of Caenorhabditis elegans caused by microbial colonization elicits a microbial aversion behavior. Bloating of the intestinal lumen also activates a broad innate immune response, even in the absence of bacterial pathogens or live bacteria.

Modulation of the extent of structural heterogeneity in α-synuclein fibrils by the small molecule thioflavin T.

The transition of intrinsically disordered, monomeric α-synuclein into β-sheet-rich oligomers and fibrils is associated with multiple neurodegenerative diseases. Fibrillar aggregates possessing distinct structures that differ in toxicity have been observed in different pathological phenotypes. Understanding the mechanism of the formation of various fibril polymorphs with differing cytotoxic effects is essential for determining how the aggregation reaction could be modulated to favor nontoxic fibrils over toxic fibrils.

Endoplasmic Reticulum Stress Caused by Lipoprotein Accumulation Suppresses Immunity against Bacterial Pathogens and Contributes to Immunosenescence.

The unfolded protein response (UPR) is a stress response pathway that is activated upon increased unfolded and/or misfolded proteins in the endoplasmic reticulum (ER), and enhanced ER stress response prolongs life span and improves immunity. However, the mechanism by which ER stress affects immunity remains poorly understood. Using the nematode , we show that mutations in the lipoproteins vitellogenins, which are homologs of human apolipoprotein B-100, resulted in upregulation of the UPR.