During aging, innate immunity progresses to a chronically active state. However, what distinguishes those that "age well" from developing age-related neurological conditions is unclear. We used Drosophila explore the cost of in aging brain. show mutations intracellular negative regulators IMD/NF-κB pathway predisposed flies toxic levels antimicrobial peptides, resulting early locomotor defects, extensive neurodegeneration, and reduced lifespan. These phenotypes were rescued when was...

Significance Infection triggers the innate immune response in all metazoans, activating regulatory pathways that result expression of effector proteins, including potent antimicrobial peptides. These can also be activated brain by aging, stress, and injury. Although nominally protective, excessive neuroinflammatory responses may themselves contribute to neurodegenerative disease mechanisms remain unclear. We found hyperactivation immunity Drosophila as a mutation or bacterial injection...

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Unfavorable TBI outcomes result from primary mechanical injuries to the ensuing secondary non-mechanical that are not limited brain. Our genome-wide association study Drosophila melanogaster revealed probability following associated with single nucleotide polymorphisms in genes involved tissue barrier function glucose homeostasis. We found causes intestinal blood–brain dysfunction highly correlated death....

ABSTRACT Drosophila C virus (DCV) is a positive-sense RNA belonging to the Dicistroviridae family. This natural pathogen of model organism melanogaster commonly used investigate antiviral host defense in flies, which involves both interference and inducible responses. Although lethality routinely as readout for efficiency immune response these studies, virus-induced pathologies flies still are poorly understood. Here, we characterize pathogenesis associated with systemic DCV infection....

Abstract Parkinson’s disease (PD) is a progressive, neurodegenerative movement disorder characterized by the loss of dopaminergic (DA) neurons. Limited understanding early molecular pathways associated with demise DA neurons, including those inflammatory exacerbation neurodegeneration, major impediment to therapeutic development. Recent studies have implicated gene-environment interactions in PD susceptibility. We used transcriptomic profiling Drosophila model response paraquat (PQ)-induced...

The effects of the cellular environment on innate immunity remain poorly characterized. Here, we show that in Drosophila ATP-sensitive potassium channels (K ATP ) mediate resistance to a cardiotropic RNA virus, Flock House virus (FHV). FHV viral load heart rapidly increases K mutant flies, leading increased viremia and accelerated death. effect is dependent interference genes Dcr-2 , AGO2 r2d2 indicating an activity associated with this channel participates antiviral pathway . Flies treated...

With emerging diseases on the rise, there is an urgent need to identify and understand novel mechanisms of prophylactic protection in vertebrate hosts. Inducing resistance against pathogens through prophylaxis ideal management strategy that may impact their host-associated microbiome. The host microbiome recognized as a critical component immunity, but effects inoculation are unknown. In this study, we investigate composition, focusing selection anti-pathogenic microbes contributing acquired...

Ranges of tardigrade intraspecific and interspecific variability are not precisely defined, both in terms morphology genetics, rendering descriptions new taxa a cumbersome task. This contribution enhances the morphological molecular dataset available for heterotardigrade genus Viridiscus by supplying information on Southern Nearctic populations V. perviridis, viridianus, species from Tennessee. We demonstrate that, putting aside already well-documented cases significant chaetotaxy, dorsal...

Previous work in our laboratory has shown that mutations prickle (pk) cause myoclonic-like seizures and ataxia Drosophila, similar to what is observed humans carrying orthologous PRICKLE genes. Here, we show pk mutant brains elevated, sustained neuronal cell death correlates with increasing seizure penetrance, as well an upregulation of mitochondrial oxidative stress innate immune response (IIR) Moreover, flies exhibiting more robust increased levels IIR-associated target gene expression...

Drosophila melanogaster has been used extensively for dissecting the genetic and functional bases of host innate antiviral immunity virus-induced pathology. Previous studies have shown that presence Wolbachia endosymbionts in D. confers resistance to infection by certain viral pathogens. Zika virus is an important vector-borne pathogen recently expanded its range due wide geographical distribution mosquito vector. Here, we describe effect on immune response adult flies following infection....

A screen for neuroprotective genes in Drosophila melanogaster led to the identification of a mutation that causes extreme, progressive loss adult brain neuropil conjunction with massive overgrowth. We mapped tumor (brat) locus, which encodes tripartite motif-NCL-1, HT2A, and LIN-41 (TRIM-NHL) RNA-binding protein established roles limiting stem cell proliferation developing ovary. However, role brat has not been described previously. The new allele, bratcheesehead (bratchs ), carries...

There is much to understand about the onset and progression of neurodegenerative diseases, including underlying genes responsible. Forward genetic screening using chemical mutagens a useful strategy for mapping mutant phenotypes among Drosophila other model organisms that share conserved cellular pathways with humans. If mutated gene interest not lethal in early developmental stages flies, climbing assay can be conducted screen phenotypic indicators decreased brain functioning, such as low...

Severe neurological complications affecting brain growth and function have been well documented in newborn adult patients infected by Zika virus (ZIKV), but the underlying mechanisms remain unknown. Here we use a Drosophila melanogaster mutant, cheesehead (chs), with mutation tumor (brat) locus that exhibits both aberrant continued proliferation progressive neurodegeneration brain. We report temperature variability is key driver of ZIKV pathogenesis, thereby altering host mortality causing...

Abstract Advanced age in humans is associated with greater susceptibility to and higher mortality rates from infections, including infections some RNA viruses. The underlying innate immune mechanisms, which represent the first line of defense against pathogens, remain incompletely understood. Drosophila melanogaster able mount potent evolutionarily conserved defenses a variety microorganisms viruses serves as an excellent model organism for studying host–pathogen interactions. With its...

Aging is accompanied by increased susceptibility to infections including with viral pathogens resulting in higher morbidity and mortality among the elderly. Significant changes host metabolism can take place following virus infection. Efficient immune responses are energetically costly, viruses divert molecular resources promote their own replication. Virus-induced metabolic reprogramming could impact infection outcomes, however, how this affected aging impacts organismal survival remains...