Pab1 acetylation at K131 decreases stress granule formation in Saccharomyces cerevisiae.

Under environmental stress, such as glucose deprivation, cells form stress granules-the accumulation of cytoplasmic aggregates of repressed translational initiation complexes, proteins, and stalled mRNAs. Recent research implicates stress granules in various diseases, such as neurodegenerative diseases, but the exact regulators responsible for the assembly and disassembly of stress granules are unknown. An important aspect of stress granule formation is the presence of posttranslational modifications on core proteins. One of those modifications is lysine acetylation, which is regulated by either a lysine acetyltransferase or a lysine deacetylase enzyme. This work deciphers the impact of lysine acetylation on an essential protein found in Saccharomyces cerevisiae stress granules, poly(A)-binding protein (Pab1). We demonstrated that an acetylation mimic of the lysine residue in position 131 reduces stress granule formation upon glucose deprivation and other stressors such as ethanol, raffinose, and vanillin. We present genetic evidence that the enzyme Rpd3 is the primary candidate for the deacetylation of Pab1-K131. Further, our electromobility shift assay studies suggest that the acetylation of Pab1-K131 negatively impacts poly(A) RNA binding. Due to the conserved nature of stress granules, therapeutics targeting the activity of lysine acetyltransferases and lysine deacetylase enzymes may be a promising route to modulate stress granule dynamics in the disease state.

Biomineralization in Cave Bacteria-Popcorn and Soda Straw Crystal Formations, Morphologies, and Potential Metabolic Pathways.

Caves are extreme, often oligotrophic, environments that house diverse groups of microorganisms. Many of these microbes can perform microbiologically induced carbonate precipitation (MICP) to form crystalline secondary cave deposits known as speleothems. The urease family is a group of enzymes involved in MICP that catalyze the breakdown of urea, which is a source of energy, into ammonia and carbonate. Carbonate anions are effluxed to the extracellular surface of the bacterium where it then binds to environmental calcium to form calcium carbonate which then continues to grow in crystal form. Here, we studied bacterial communities from speleothems collected from the Iron Curtain Cave (ICC) in Chilliwack, B.C., Canada, to characterize these organisms and determine whether urease-positive (U+) bacteria were present in the cave and their potential impact on speleothem formation. The ICC is a carbonate cave located on the northside of Chipmunk Ridge, presenting a unique environment with high iron content sediment and limestone structures throughout. With six pools of water throughout the cave, the environment is highly humid, with temperatures ranging between 4 and 12°C depending on the time of year. Ninety-nine bacterial strains were isolated from popcorn (PCS) and soda straw (SSS) speleothems. These isolates were screened for urease enzymatic activity, with 11 candidates found to be urease-positive. After incubation, species-specific crystal morphologies were observed. Popcorn speleothem provided more bacterial diversity overall when compared to soda straw speleothem when examined under a culture-based method. Nearly twice as many U+ isolates were isolated from popcorn speleothems compared to soda straw speleothems. The U+ candidates were identified to the genus level by 16S rRNA analysis, and two isolates underwent whole-genome sequencing. Two novel species were identified as Sphingobacterium sp. PCS056 and Pseudarthrobacter sp. SSS035. Both isolates demonstrated the most crystal production as well as the most morphologically dissimilar crystal shapes in broth culture and were found to produce crystals as previously observed in both agar and broth media. The results from this study are consistent with the involvement of urease-positive bacteria isolated from the ICC in the formation of cave speleothems. 16S rRNA sequencing revealed a diverse set of microbes inhabiting the speleothems that have urease activity. Whole-genome sequencing of the two chosen isolates confirmed the presence of urease pathways, while revealing differences in urease pathway structure and number. This research contributes to understanding microbial-associated cave formation and degradation, with applications to cave conservation, microbiota composition, and their role in shaping the cave environment.

Small Towns, Big Cities: Rural and Urban Disparities Among Hospitalized Patients With COVID-19 in the Central Savannah River Area.

BACKGROUND: There is a lack of data surrounding the impact of coronavirus disease 2019 (COVID-19) among rural and urban communities. This study aims to determine whether there are differences in epidemiologic characteristics and clinical outcomes among individuals with COVID-19 among these communities. METHODS: This was a retrospective analysis of 155 patients admitted to a single-center tertiary academic hospital located in Augusta, Georgia, with a large proportion of hospitalized patients transferred from or residing in rural and urban counties. Hospitalized adult patients were included in the study if they were admitted to AUMC between March 13, 2020, and June 25, 2020, and had a positive polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 regardless of the presence or absence of symptomatology. Demographics, admission data, and 30-day outcomes were examined overall and by geographical variation. RESULTS: Urban patients were more likely to be admitted to the general medical floor (P = .01), while rural patients were more likely to require an escalation in the level of care within 24 hours of admission (P = .02). In contrast, of the patients who were discharged or expired at day 30, there were no statistically significant differences in either total hospital length of stay or intensive care unit length of stay between the populations. CONCLUSIONS: There may be many social determinants of health that limit a rural patient's ability to seek prompt medical care and contribute to decompensation within the first 24 hours of admission. This study provides insight into the differences in clinical course among patients admitted from different community settings and when accounting for comorbid conditions.

Duration of Symptoms Does Not Affect Clinical Outcome After Lumbar Arthrodesis.

STUDY DESIGN: Retrospective cohort study at a single institution. OBJECTIVE: To examine the effect of symptom duration on clinical outcomes after posterolateral lumbar fusion. SUMMARY OF BACKGROUND DATA: Nonoperative measures are generally exhausted before patients are indicated for surgical intervention, leaving patients with their symptomatology for varying lengths of time. It is unclear at what point in time surgical intervention may become less efficacious at alleviating preoperative symptoms. MATERIALS AND METHODS: Consecutive patients who underwent primary elective open posterior lumbar spinal fusion at a single academic institution were included. Patient and operative characteristics were compared between symptom duration groups (group 1: <12 mo of pain, group 2: ≥12 mo of pain). Preoperative and final postoperative visual analog scale back/leg pain, and Oswestry Disability Index, were collected. Preoperative, immediate postoperative, and final radiographs were assessed to measure lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), and the PI-LL difference was calculated. RESULTS: In total, 167 patients were included in group 1, whereas 359 patients were included in group 2. Baseline demographics and operative characteristics were similar between the 2 groups. Both groups had similar changes in sagittal parameters and had no significant difference in rates of complication, reoperation, discharge to rehabilitation facility, or early adjacent segment degeneration. Both groups demonstrated similar improvement in clinical outcome measures. CONCLUSIONS: Despite differences in symptom duration, patients who had pain for ≥12 months demonstrated similar improvement after posterolateral lumbar arthrodesis than those who had pain for <12 months. Extended effort of conservative treatments or delay of operative intervention does not appear to negatively impact the eventual outcome of surgery. LEVEL OF EVIDENCE: Level III.

Measles Outbreak in Unvaccinated and Partially Vaccinated Children and Adults in the United States and Canada (2018-2019): A Narrative Review of Cases.

Since 2018 and currently in 2019, the United States and Canada experienced a rapidly spreading measles virus outbreak. The developing outbreak may be due to a lack of vaccination, an inadequate dosage of measles (MMR) vaccine, clusters of intentionally under-vaccinated children, imported measles from global travel, and from those who are immunocompromised or have other life-threatening diseases. The infection originated mainly from travelers who acquired measles abroad and has thus led to a major outbreak and health concern not only in the United States and Canada but also in other parts of the world. According to World Health Organization, from January 2019 through September 2019, 1234 cases of measles have been reported in the United States and 91 reported cases in Canada, while in 2018, 372 and 28 cases were reported in the United States and Canada, respectively. A potential driving factor to the increased cases maybe because fewer children have been vaccinated over the last number of years in both countries. This article is a narrative review of cases discussing the measles outbreak among partially vaccinated and unvaccinated children and adults in the United States and Canada in 2018 and 2019.

Whole Genome Sequencing and Metabolomic Study of Cave Streptomyces Isolates ICC1 and ICC4.

The terrestrial subsurface microbiome has gained considerable amount of interests in the recent years because of its rich potential resource for biomining novel genes coding for metabolites possessing antimicrobial activities. In our previous study, we identified two Streptomyces isolates, designated as ICC1 and ICC4, from the Iron Curtain Cave, Chilliwack, Canada that exhibited antagonistic activities against the multidrug resistant strains of Escherichia coli. In this study, the genomes of these two isolates were sequenced by Illumina MiSeq, assembled and annotated. The genes associated with secondary metabolite production were identified and annotated using the bioinformatics platforms antiSMASH and BAGEL. ICC1 and ICC4 were then cultivated and ICC1 metabolome characterized by UHPLC-ESI-HRMS. The Global Natural Products Social Molecular Networking was used to identify metabolites based on the MS/MS spectral data. ICC1 and ICC4 showed a high level of sequence identity with the terrestrial bacteria Streptomyces lavendulae; however, they possess a greater secondary metabolite potential as estimated by the total number of identified biosynthetic gene clusters (BGCs). In particular, ICC1 and ICC4 had a greater number of polyketide and non-ribosomal peptide BGCs. The most frequently detected BGCs were those predicted to generate terpenes, small and low complexity dipeptides and lipids. Spectral analysis clearly identified a number of diketopiperazine products through matched reference spectra for cyclo (Leu-Pro), cyclo (Pro-Val) and cyclo [(4-hydroxyPro)-Leu]. One of the terpenes gene clusters predicted by antiSMASH possesses a seven-gene pathway consistent with diazepinomicin biosynthesis. This molecule contains a very rare core structure and its BGC, to date, has only been identified from a single bacterial genome. The tetrapeptide siderophore coelichelin BGC was unambiguously identified in the genome, however, the metabolite could not be identified from the culture extracts. Two type III polyketides, 2', 5' - dimethoxyflavone and nordentatin, were identified from the UHPLC-HRMS data of the aqueous and n-butanolic fractions of Streptomyces sp. ICC1, respectively. A BGC likely encoding these metabolites was predicted in both genomes. The predicted similarities in molecule production and genome shared by these two strains could be an indicative of a cooperative mode of living in extreme habitats instead of a competitive one. This secondary metabolite potential may contribute to the fitness of ICC1 and ICC4 in the Iron Curtain Cave.

Draft Genome Sequence of the Type Strain Streptomyces armeniacus ATCC 15676.

The Streptomyces genus represents a prolific and significant source for secondary metabolite discovery. Here, we report a de novo assembly and draft genome sequence for the type strain Streptomyces armeniacus ATCC 15676.

Draft Genome Sequence of Streptomyces sp. Strain PBH53, Isolated from an Urban Environment.

We report the draft genome sequence of Streptomyces sp. strain PBH53, a strain isolated from an urban transit station in Ottawa, Canada. The analysis of the genome using the bioinformatics tool antiSMASH showed the presence of many unique natural product biosynthetic pathways.