Publications by authors named "Richard Helm"

Post-traumatic stress disorder (PTSD) is a severe anxiety disorder that affects women more than men. About 30% of patients suffering from PTSD develop the disorder by witnessing a traumatic event happen to someone else. However, as the focus has remained on those directly experiencing the traumatic event, whether indirectly acquired fear memories that underlie PTSD have the same molecular signature as those that are directly acquired remains unknown.

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Over 90% of protein degradation in eukaryotic cells occurs through the ubiquitin-proteasome system (UPS). In this system, the ubiquitin protein can bind to a substrate on its own or it can form a chain with multiple ubiquitin molecules in a process called polyubiquitination. There are 8 different sites on ubiquitin at which polyubiquitin chains can be formed, the second most abundant of which, lysine-63 (K63), is independent of the degradation process, though this mark has rarely been studied in the brain or during learning-dependent synaptic plasticity.

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Auxins are crucial signaling molecules that regulate the growth, metabolism, and behavior of various organisms, most notably plants but also bacteria, fungi, and animals. Many microbes synthesize and perceive auxins, primarily indole-3-acetic acid (IAA, referred to as auxin herein), the most prevalent natural auxin, which influences their ability to colonize plants and animals. Understanding auxin biosynthesis and signaling in fungi may allow us to better control interkingdom relationships and microbiomes from agricultural soils to the human gut.

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Article Synopsis
  • Most bacteria have a cell wall made of peptidoglycan, which consists of glycan strands linked by peptide cross-links, primarily classified as 4-3 and 3-3 based on their amino acid composition.
  • The majority of bacteria rely on 4-3 cross-links for survival, but in a specific intestinal pathogen, 3-3 cross-links are essential, making L,D-transpeptidases (LDTs) crucial for its viability.
  • This study identifies a new family of PG cross-linking enzymes, reveals the function of VanW domains, and highlights the potential of targeting LDTs for antibiotic development against this pathogen.
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Cu is an antimicrobial that is commonly applied to premise (i.e., building) plumbing systems for control, but the precise mechanisms of inactivation are not well defined.

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The ubiquitin-proteasome system (UPS) controls the majority of protein degradation in cells and dysregulation of the UPS has been implicated in the pathophysiology of numerous neurodegenerative disorders, including Alzheimer's disease. Further, strong evidence supports a critical role for the UPS in synaptic plasticity and memory formation. However, while proteasome function is known to decrease broadly in the brain across the lifespan, whether it changes in the hippocampus, a region critical for memory storage and among the first impacted in Alzheimer's disease, at rest and following learning in the aged brain remains unknown.

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The behavioral endocrinology associated with reproduction and uniparental male care has been studied in teleosts, but little is known about hormonal correlates of uniparental male care in other ectotherms. To address this gap, we are the first to document the seasonal steroid endocrinology of uniparental male hellbender salamanders during the transition from pre-breeding to nest initiation, and through the subsequent eight months of paternal care. In doing so, we investigated the correlates of nest fate and clutch size, exploring hellbenders' alignment with several endocrinological patterns observed in uniparental male fish.

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Article Synopsis
  • The text discusses a specific bacterium known for causing antibiotic-associated diarrhea, which strengthens its cell wall using 3-3 crosslinks created by L,D-transpeptidases (LDTs), unlike most bacteria that use 4-3 crosslinks.
  • Researchers found that 3-3 crosslinking is vital for the survival of this bacterium and discovered a new type of LDT that uses a VanW domain to facilitate this process.
  • The study suggests that targeting LDTs could lead to new antibiotics that effectively kill this bacterium while preserving the beneficial intestinal bacteria.
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Microbial extracellular proteins and metabolites provide valuable information concerning how microbes adapt to changing environments. In cyanobacteria, dynamic acclimation strategies involve a variety of regulatory mechanisms, being ferric uptake regulator proteins as key players in this process. In the nitrogen-fixing cyanobacterium sp.

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Background: Sex differences have been observed in several brain regions for the molecular mechanisms involved in baseline (resting) and memory-related processes. The ubiquitin proteasome system (UPS) is a major protein degradation pathway in cells. Sex differences have been observed in lysine-48 (K48)-polyubiquitination, the canonical degradation mark of the UPS, both at baseline and during fear memory formation within the amygdala.

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Glycosidic linkages in oligosaccharides play essential roles in determining their chemical properties and biological activities. MS has been widely used to infer glycosidic linkages but requires a substantial amount of starting material, which limits its application. In addition, there is a lack of rigorous research on what MS protocols are proper for characterizing glycosidic linkages.

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Females are more likely than males to develop post-traumatic stress disorder (PTSD). However, the neurobiological mechanisms responsible for these sex differences remain elusive. The ubiquitin proteasome system (UPS) is involved in fear memory formation and implicated in PTSD development.

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CADD (chlamydia protein associating with death domains) is a p-aminobenzoate (pAB) synthase involved in a noncanonical route for tetrahydrofolate biosynthesis in Chlamydia trachomatis. Although previously implicated to employ a diiron cofactor, here, we show that pAB synthesis by CADD requires manganese and the physiological cofactor is most likely a heterodinuclear Mn/Fe cluster. Isotope-labeling experiments revealed that the two oxygen atoms in the carboxylic acid portion of pAB are derived from molecular oxygen.

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Insulin resistance and progressive decline in functional β-cell mass are two key factors for developing type 2 diabetes (T2D), which is largely driven by overweight and obesity, a significant obstacle for effective metabolic control in many patients with T2D. Thus, agents that simultaneously ameliorate obesity and act on multiple pathophysiological components could be more effective for treating T2D. Here, we report that elenolic acid (EA), a phytochemical, is such a dual-action agent.

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A range of neurodegenerative and related aging diseases, such as Alzheimer's disease and type 2 diabetes, are linked to toxic protein aggregation. Yet the mechanisms of protein aggregation inhibition by small molecule inhibitors remain poorly understood, in part because most protein targets of aggregation assembly are partially unfolded or intrinsically disordered, which hinders detailed structural characterization of protein-inhibitor complexes and structural-based inhibitor design. Herein we employed a parallel small molecule library-screening approach to identify inhibitors against three prototype amyloidogenic proteins in neurodegeneration and related proteinopathies: amylin, Aβ and tau.

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Tau aggregates are present in multiple neurodegenerative diseases known as "tauopathies," including Alzheimer's disease, Pick's disease, progressive supranuclear palsy, and corticobasal degeneration. Such misfolded tau aggregates are therefore potential sources for selective detection and biomarker discovery. Six human tau isoforms present in brain tissues and both 3R and 4R isoforms have been observed in the neuronal inclusions.

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Strong evidence has implicated ubiquitin signaling in the process of fear memory formation. While less abundant than ubiquitination, evidence suggests that protein SUMOylation may also be involved in fear memory formation in neurons. However, the importance of amygdala protein SUMOylation in fear memory formation has never been directly examined.

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The distribution of the black rat (Rattus rattus) has been heavily influenced by its association with humans. The dispersal history of this non-native commensal rodent across Europe, however, remains poorly understood, and different introductions may have occurred during the Roman and medieval periods. Here, in order to reconstruct the population history of European black rats, we first generate a de novo genome assembly of the black rat.

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Peptidoglycan-a mesh sac of glycans that are linked by peptides-is the main component of bacterial cell walls. Peptidoglycan provides structural strength, protects cells from osmotic pressure and contributes to shape. All bacterial glycans are repeating disaccharides of N-acetylglucosamine (GlcNAc) β-(1-4)-linked to N-acetylmuramic acid (MurNAc).

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Ubiquitin-proteasome mediated protein degradation has been widely implicated in fear memory formation in the amygdala. However, to date, the protein targets of the proteasome remain largely unknown, limiting our understanding of the functional significance for protein degradation in fear memory formation. Additionally, whether similar proteins are targeted by the proteasome between sexes has yet to be explored.

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Interactions between plants and leaf herbivores have long been implicated as the major driver of plant secondary metabolite diversity. However, other plant-animal interactions, such as those between fruits and frugivores, may also be involved in phytochemical diversification. Using 12 species of , we conducted untargeted metabolomics and molecular networking with extracts of fruits and leaves.

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Seasonally breeding species exhibit cyclical changes in circulating steroid hormone profiles that correspond with changes to their reproductive behavior and ecology. Such information is critical to the conservation of imperiled and data-deficient species, such as the eastern hellbender salamander (Cryptobranchus alleganiensis alleganiensis). We determined changes in plasma testosterone (T), dihydrotestosterone (DHT), 11-ketotestosterone (11-KT), 11-ketoandrostenedione (11-KA), dehydroepiandrosterone (DHEA), cortisol, corticosterone, and progesterone (P) during a four-month period preceding breeding in adult male and female eastern hellbenders.

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Strong evidence supports that protein ubiquitination is a critical regulator of fear memory formation. However, as this work has focused on protein degradation, it is currently unknown whether polyubiquitin modifications that are independent of the proteasome are involved in learning-dependent synaptic plasticity. Here, we present the first evidence that atypical linear (M1) polyubiquitination, the only ubiquitin chain that does not occur at a lysine site and is largely independent of the proteasome, is critically involved in contextual fear memory formation in the amygdala in a sex-specific manner.

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Strong evidence supports a role for protein degradation in fear memory formation. However, these data have been largely done in only male animals. Here, we found that following contextual fear conditioning, females, but not males, had increased levels of proteasome activity and K48 polyubiquitin protein targeting in the dorsal hippocampus, the latter of which occurred at chaperones or RNA processing proteins.

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Chemoreceptors enable the legume symbiont Sinorhizobium meliloti to detect and respond to specific chemicals released from their host plant alfalfa, which allows the establishment of a nitrogen-fixing symbiosis. The periplasmic region (PR) of transmembrane chemoreceptors act as the sensory input module for chemotaxis systems via binding of specific ligands, either directly or indirectly. S.

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