Unprecedented toxic blooms of Microcystis spp. in 2019 in the Chowan River, North Carolina.

The Chowan River flows from southern Virginia through northeastern North Carolina and into the Albemarle Sound, a part of the second largest U.S. estuary.

Phage resistance mutations affecting the bacterial cell surface increase susceptibility to fungi in a model cheese community.

Diverse populations of bacteriophages infect and coevolve with their bacterial hosts. Although host recognition and infection occur within microbiomes, the molecular mechanisms underlying host-phage interactions within a community context remain poorly studied. The biofilms (rinds) of aged cheeses contain taxonomically diverse microbial communities that follow reproducible growth patterns and can be manipulated under laboratory conditions.

Microcystin Concentrations, Partitioning, and Structural Composition during Active Growth and Decline: A Laboratory Study.

Microcystin can be present in variable concentrations, phases (dissolved and particulate), and structural forms (congeners), all which impact the toxicity and persistence of the algal metabolite. Conducting incubation experiments with six bloom assemblages collected from the Chowan River, North Carolina, we assessed microcystin dynamics during active growth and biomass degradation. Upon collection, average particulate and dissolved microcystin ranged between 0.

Metabolomics of bacterial-fungal pairwise interactions reveal conserved molecular mechanisms.

Bacterial-fungal interactions (BFIs) can shape the structure of microbial communities, but the small molecules mediating these BFIs are often understudied. We explored various optimization steps for our microbial culture and chemical extraction protocols for bacterial-fungal co-cultures, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed that metabolomic profiles are mainly comprised of fungi derived features, indicating that fungi are the key contributors to small molecules in BFIs. LC-inductively coupled plasma MS (LC-ICP-MS) and MS/MS based dereplication using database searching revealed the presence of several known fungal specialized metabolites and structurally related analogues in these extracts, including siderophores such as desferrichrome, desferricoprogen, and palmitoylcoprogen.

Metabolomics of bacterial-fungal pairwise interactions reveal conserved molecular mechanisms.

Bacterial-fungal interactions (BFIs) can shape the structure of microbial communities, but the small molecules mediating these BFIs are often understudied. We explored various optimization steps for our microbial culture and chemical extraction protocols for bacterial-fungal co-cultures, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed that metabolomic profiles are mainly comprised of fungi derived features, indicating that fungi are the key contributors to small molecule mediated BFIs. LC-inductively coupled plasma MS (LC-ICP-MS) and MS/MS based dereplication using database searching revealed the presence of several known fungal specialized metabolites and structurally related analogues in these extracts, including siderophores such as desferrichrome, desferricoprogen, and palmitoylcoprogen.

Longitudinal, Multi-Platform Metagenomics Yields a High-Quality Genomic Catalog and Guides an Model for Cheese Communities.

Microbiomes are intricately intertwined with human health, geochemical cycles, and food production. While many microbiomes of interest are highly complex and experimentally intractable, cheese rind microbiomes have proven to be powerful model systems for the study of microbial interactions. To provide a more comprehensive view of the genomic potential and temporal dynamics of cheese rind communities, we combined longitudinal, multi-platform metagenomics of three ripening washed-rind cheeses with whole-genome sequencing of community isolates.

Pediatric Headache Experience During the COVID-19 Pandemic.

Objective: Headache disorders are exceedingly common in children and adolescents. The association between headaches, emotional stress, and disruptions in daily routines are well established. The goal of this study is to compare the experiences of patients with a preexisting diagnosis of a primary headache disorder in terms of headache frequency and severity, lifestyle techniques for headache prevention, screen use, and mood from before and after the onset of the COVID-19 pandemic.

Pediatric screen exposure and school related headache disability.

Background And Objectives: Prolonged screen exposure is often cited as a trigger for pediatric headache. We present initial findings evaluating the association between adolescent screen use type, duration, and school disability.

Methods: New patients aged 12-17 years presenting to a headache clinic were screened and surveyed regarding headache characteristics, behavioral habits, school attendance, and screen utilization.

Criterion Validity and Reliability of Knee Frontal Plane Projection Angles Measured Using the Technique Application.

Context: Abnormal knee frontal plane projection angles (FPPA) during movement have been associated with patellofemoral pain. As such, clinicians are interested in valid and reliable instruments suitable for broad-based clinical use that allow them to objectively measure such variables. Therefore, the purpose of the current study was to examine the criterion validity and reliability of knee FPPA measures obtained by clinicians using a free tablet application called Technique.

Natural History of Abortive Medication Withdrawal in the Management of Pediatric Medication Overuse Headache.

Objective: The objective of this study is to document pain scores during withdrawal of abortive medication in patients diagnosed with medication overuse headache.

Design: Cross-sectional study.

Setting: Children's National Hospital's Headache Program.

Putting microbial interactions back into community contexts.

Microbial interactions are key aspects of the biology of microbiomes. Recently, there has been a shift in the field towards studying interactions in more representative contexts, whether using multispecies model microbial communities or by looking at interactions in situ. Across diverse microbial systems, these studies have begun to identify common interaction mechanisms.

New Daily Persistent Headache in a Pediatric Population.

Introduction: New daily persistent headache (NDPH) is a primary headache disorder characterized by an intractable, daily, and unremitting headache lasting for at least 3 months. Currently, there are limited studies in the pediatric population describing the characteristics of NDPH.

Objective: The objective of the current study is to describe the characteristics of NDPH in pediatric patients presenting to a headache program at a tertiary referral center.

A community resource for paired genomic and metabolomic data mining.

Genomics and metabolomics are widely used to explore specialized metabolite diversity. The Paired Omics Data Platform is a community initiative to systematically document links between metabolome and (meta)genome data, aiding identification of natural product biosynthetic origins and metabolite structures.

Bacterial-fungal interactions revealed by genome-wide analysis of bacterial mutant fitness.

Microbial interactions are expected to be major determinants of microbiome structure and function. Although fungi are found in diverse microbiomes, their interactions with bacteria remain largely uncharacterized. In this work, we characterize interactions in 16 different bacterial-fungal pairs, examining the impacts of 8 different fungi isolated from cheese rind microbiomes on 2 bacteria (Escherichia coli and a cheese-isolated Pseudomonas psychrophila).

Interaction of oxidative stress and neurotrauma in ALDH2 mice causes significant and persistent behavioral and pro-inflammatory effects in a tractable model of mild traumatic brain injury.

Oxidative stress induced by lipid peroxidation products (LPP) accompanies aging and has been hypothesized to exacerbate the secondary cascade in traumatic brain injury (TBI). Increased oxidative stress is a contributor to loss of neural reserve that defines the ability to maintain healthy cognitive function despite the accumulation of neuropathology. ALDH2 mice are unable to clear aldehyde LPP by mitochondrial aldehyde dehydrogenase-2 (Aldh2) detoxification and provide a model to study mild TBI (mTBI), therapeutic interventions, and underlying mechanisms.

Interaction with the justice system and other factors associated with pregnant women's self-report and continuation of use of marijuana.

Background: Marijuana use in pregnancy is common and self-report of use to healthcare providers is variable. This study evaluates the relationship between prior interaction with the justice system as well as other factors associated with self-report and continuation of use of marijuana in pregnancy.

Methods: This retrospective cohort study included women with a positive urine toxicology test for marijuana at their initial prenatal visit.

BLANKA: an Algorithm for Blank Subtraction in Mass Spectrometry of Complex Biological Samples.

Multispecies microbiome systems are known to be closely linked to human, animal, and plant life processes. The growing field of metabolomics presents the opportunity to detect changes in overall metabolomic profiles of microbial species interactions. These metabolomic changes provide insight into function of metabolites as they correlate to different species presence and the observed phenotypic changes, but detection of subtle changes is often difficult in samples with complex backgrounds.

Changes in the genetic requirements for microbial interactions with increasing community complexity.

Microbial community structure and function rely on complex interactions whose underlying molecular mechanisms are poorly understood. To investigate these interactions in a simple microbiome, we introduced into an experimental community based on a cheese rind and identified the differences in s genetic requirements for growth in interactive and non-interactive contexts using Random Barcode Transposon Sequencing (RB-TnSeq) and RNASeq. Genetic requirements varied among pairwise growth conditions and between pairwise and community conditions.

High-throughput interaction screens illuminate the role of c-di-AMP in cyanobacterial nighttime survival.

The broadly conserved signaling nucleotide cyclic di-adenosine monophosphate (c-di-AMP) is essential for viability in most bacteria where it has been studied. However, characterization of the cellular functions and metabolism of c-di-AMP has largely been confined to the class Bacilli, limiting our functional understanding of the molecule among diverse phyla. We identified the cyclase responsible for c-di-AMP synthesis and characterized the molecule's role in survival of darkness in the model photosynthetic cyanobacterium Synechococcus elongatus PCC 7942.

Tendon transfer to unossified bone in a porcine model: potential implications for early tibialis anterior tendon transfers in children with clubfeet.

Purpose: Tibialis anterior tendon transfers (TATT) are commonly performed in young children following Ponseti casting for clubfeet. The classic TATT involves advancing the tendon through a hole drilled in the ossified cuneiform. The aim of this study was to determine if tendons transferred through unossified bones have untoward effects on subsequent bone development.

Variation of the aryl substituent on the piperazine ring within the 4-(piperazin-1-yl)-2,6-di(pyrrolidin-1-yl)pyrimidine scaffold unveils potent, non-competitive inhibitors of the inflammatory caspases.

The inflammatory caspases (caspase-1, -4 and -5) are potential therapeutic targets for autoimmune and inflammatory diseases due to their involvement in the immune response upon inflammasome formation. A series of small molecules based on the 4-(piperazin-1-yl)-2,6-di(pyrrolidin-1-yl)pyrimidine scaffold were synthesized with varying substituents on the piperazine ring. Several compounds were pan-selective inhibitors of the inflammatory caspases, caspase-1, -4 and -5, with the ethylbenzene derivative CK-1-41 displaying low nanomolar K values across this family of caspases.

Prodrugs Bioactivated to Quinones Target NF-κB and Multiple Protein Networks: Identification of the Quinonome.

Electrophilic reactive intermediates resulting from drug metabolism have been associated with toxicity and off-target effects and in some drug discovery programs trigger NO-GO decisions. Many botanicals and dietary supplements are replete with such reactive electrophiles, notably Michael acceptors, which have been demonstrated to elicit chemopreventive mechanisms; and Michael acceptors are gaining regulatory approval as contemporary cancer therapeutics. Identifying protein targets of these electrophiles is central to understanding potential therapeutic benefit and toxicity risk.

Ketocarotenoid Production in Soybean Seeds through Metabolic Engineering.

The pink or red ketocarotenoids, canthaxanthin and astaxanthin, are used as feed additives in the poultry and aquaculture industries as a source of egg yolk and flesh pigmentation, as farmed animals do not have access to the carotenoid sources of their wild counterparts. Because soybean is already an important component in animal feed, production of these carotenoids in soybean could be a cost-effective means of delivery. In order to characterize the ability of soybean seed to produce carotenoids, soybean cv.

Phase 1 trial of carfilzomib (PR-171) in combination with vorinostat (SAHA) in patients with relapsed or refractory B-cell lymphomas.

A phase 1 study with carfilzomib and vorinostat was conducted in 20 B-cell lymphoma patients. Vorinostat was given orally twice daily on days 1, 2, 3, 8, 9, 10, 15, 16, and 17 followed by carfilzomib (given as a 30-min infusion) on days 1, 2, 8, 9, 15, and 16. A treatment cycle was 28 days.

Using Representational Difference Analysis to detect changes in transcript expression of Aiptasia genes after laboratory exposure to lindane.

Molecular stress responses to pesticide exposures represent an understudied area of cnidarian transcriptome investigations. The organochlorine pesticide lindane is known to disrupt normal neuron function. Cnidarians with simple nervous systems are recognized as sensitive indicators of water quality, yet nothing is known about cnidarian responses to lindane.