ERK2 alone drives inflammatory pain but cooperates with ERK1 in sensory neuron survival

Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are highly homologous yet distinct components of signal transduction pathways known to regulate cell survival and function. Recent evidence indicates an isoform-specific role for ERK2 in pain processing and peripheral sensitization. However, the function of ERK2 in primary sensory neurons has not been directly tested. To dissect the isoform-specific function of ERK2 in sensory neurons, we used mice with Cre-loxP-mediated deletion of ERK2 in Na(v)1.8(+) sensory neurons that are predominantly nociceptors. We find that ERK2, unlike ERK1, is required for peripheral sensitization and cold sensation. We also demonstrate that ERK2, but not ERK1, is required to preserve epidermal innervation in a subset of peptidergic neurons. Additionally, deletion of both ERK isoforms in Na(v)1.8(+) sensory neurons leads to neuron loss not observed with deletion of either isoform alone, demonstrating functional redundancy in the maintenance of sensory neuron survival. Thus, ERK1 and ERK2 exhibit both functionally distinct and redundant roles in sensory neurons. SIGNIFICANCE STATEMENT ERK1/2 signaling affects sensory neuron function and survival. However, it was not clear whether ERK isoform-specific roles exist in these processes postnatally. Previous work from our laboratory suggested either functional redundancy of ERK isoforms or a predominant role for ERK2 in pain; however, the tools to discriminate between these possibilities were not available at the time. In the present study, we use new genetic knock-out lines to demonstrate that ERK2 in sensory neurons is necessary for development of inflammatory pain and for postnatal maintenance of peptidergic epidermal innervation. Interestingly, postnatal loss of both ERK isoforms leads to a profound loss of sensory neurons. Therefore, ERK1 and ERK2 display both functionally distinct and redundant roles in sensory neurons

Accuracy of energy and nutrient intake estimation versus observed intake using 4 technology-assisted dietary assessment methods: A randomized crossover feeding study

Background: Technology-assisted 24-h dietary recalls (24HRs) have been widely adopted in population nutrition surveillance. Evaluations of 24HRs inform improvements, but direct comparisons of 24HR methods for accuracy in reference to a measure of true intake are rarely undertaken in a single study population. Objectives: To compare the accuracy of energy and nutrient intake estimation of 4 technology-assisted dietary assessment methods relative to true intake across breakfast, lunch, and dinner. Methods: In a controlled feeding study with a crossover design, 152 participants [55% women; mean age 32 y, standard deviation (SD) 11; mean body mass index 26 kg/m2, SD 5] were randomized to 1 of 3 separate feeding days to consume breakfast, lunch, and dinner, with unobtrusive weighing of foods and beverages consumed. Participants undertook a 24HR the following day [Automated Self-Administered Dietary Assessment Tool-Australia (ASA24); Intake24-Australia; mobile Food Record-Trained Analyst (mFR-TA); or Image-Assisted Interviewer-Administered 24-hour recall (IA-24HR)]. When assigned to IA-24HR, participants referred to images captured of their meals using the mobile Food Record (mFR) app. True and estimated energy and nutrient intakes were compared, and differences among methods were assessed using linear mixed models. Results: The mean difference between true and estimated energy intake as a percentage of true intake was 5.4% (95% CI: 0.6, 10.2%) using ASA24, 1.7% (95% CI: −2.9, 6.3%) using Intake24, 1.3% (95% CI: −1.1, 3.8%) using mFR-TA, and 15.0% (95% CI: 11.6, 18.3%) using IA-24HR. The variances of estimated and true energy intakes were statistically significantly different for all methods (P \u3c 0.01) except Intake24 (P = 0.1). Differential accuracy in nutrient estimation was present among the methods. Conclusions: Under controlled conditions, Intake24, ASA24, and mFR-TA estimated average energy and nutrient intakes with reasonable validity, but intake distributions were estimated accurately by Intake24 only (energy and protein). This study may inform considerations regarding instruments of choice in future population surveillance. This trial was registered at Australian New Zealand Clinical Trials Registry as ACTRN12621000209897

The scale of population structure in Arabidopsis thaliana

The population structure of an organism reflects its evolutionary history and influences its evolutionary trajectory. It constrains the combination of genetic diversity and reveals patterns of past gene flow. Understanding it is a prerequisite for detecting genomic regions under selection, predicting the effect of population disturbances, or modeling gene flow. This paper examines the detailed global population structure of Arabidopsis thaliana. Using a set of 5,707 plants collected from around the globe and genotyped at 149 SNPs, we show that while A. thaliana as a species self-fertilizes 97% of the time, there is considerable variation among local groups. This level of outcrossing greatly limits observed heterozygosity but is sufficient to generate considerable local haplotypic diversity. We also find that in its native Eurasian range A. thaliana exhibits continuous isolation by distance at every geographic scale without natural breaks corresponding to classical notions of populations. By contrast, in North America, where it exists as an exotic species, A. thaliana exhibits little or no population structure at a continental scale but local isolation by distance that extends hundreds of km. This suggests a pattern for the development of isolation by distance that can establish itself shortly after an organism fills a new habitat range. It also raises questions about the general applicability of many standard population genetics models. Any model based on discrete clusters of interchangeable individuals will be an uneasy fit to organisms like A. thaliana which exhibit continuous isolation by distance on many scales

A genome triplication associated with early diversification of the core eudicots

Background: Although it is agreed that a major polyploidy event, gamma, occurred within the eudicots, the phylogenetic placement of the event remains unclear. Results: To determine when this polyploidization occurred relative to speciation events in angiosperm history, we employed a phylogenomic approach to investigate the timing of gene set duplications located on syntenic gamma blocks. We populated 769 putative gene families with large sets of homologs obtained from public transcriptomes of basal angiosperms, magnoliids, asterids, and more than 91.8 gigabases of new next-generation transcriptome sequences of non-grass monocots and basal eudicots. The overwhelming majority (95%) of well-resolved gamma duplications was placed before the separation of rosids and asterids and after the split of monocots and eudicots, providing strong evidence that the gamma polyploidy event occurred early in eudicot evolution. Further, the majority of gene duplications was placed after the divergence of the Ranunculales and core eudicots, indicating that the gamma appears to be restricted to core eudicots. Molecular dating estimates indicate that the duplication events were intensely concentrated around 117 million years ago. Conclusions: The rapid radiation of core eudicot lineages that gave rise to nearly 75% of angiosperm species appears to have occurred coincidentally or shortly following the gamma triplication event. Reconciliation of gene trees with a species phylogeny can elucidate the timing of major events in genome evolution, even when genome sequences are only available for a subset of species represented in the gene trees. Comprehensive transcriptome datasets are valuable complements to genome sequences for high-resolution phylogenomic analysis

A Selective Antibiotic for Lyme Disease

Lyme disease is on the rise. Caused by a spirochete Borreliella burgdorferi, it affects an estimated 500,000 people in the United States alone. The antibiotics currently used to treat Lyme disease are broad spectrum, damage the microbiome, and select for resistance in non-target bacteria. We therefore sought to identify a compound acting selectively against B. burgdorferi. A screen of soil micro-organisms revealed a compound highly selective against spirochetes, including B. burgdorferi. Unexpectedly, this compound was determined to be hygromycin A, a known antimicrobial produced by Streptomyces hygroscopicus. Hygromycin A targets the ribosomes and is taken up by B. burgdorferi, explaining its selectivity. Hygromycin A cleared the B. burgdorferi infection in mice, including animals that ingested the compound in a bait, and was less disruptive to the fecal microbiome than clinically relevant antibiotics. This selective antibiotic holds the promise of providing a better therapeutic for Lyme disease and eradicating it in the environment

Tackling health literacy: adaptation of public hypertension educational materials for an Indo-Asian population in Canada

<p>Abstract</p> <p>Background</p> <p>Indo-Asians in Canada are at increased risk for cardiovascular diseases. There is a need for cultural and language specific educational materials relating to this risk. During this project we developed and field tested the acceptability of a hypertension public education pamphlet tailored to fit the needs of an at risk local Indo-Asian population, in Calgary, Alberta, Canada.</p> <p>Methods</p> <p>A community health board representing Calgary's Indo-Asian communities identified the culturally specific educational needs and language preferences of the local population. An adaptation of an existing English language Canadian Public Hypertension Recommendations pamphlet was created considering the literacy and translation challenges. The adapted pamphlet was translated into four Indo-Asian languages. The adapted pamphlets were disseminated as part of the initial educational component of a community-based culturally and language-sensitive cardiovascular risk factor screening and management program. Field testing of the materials was undertaken when participants returned for program follow-up seven to 12 months later.</p> <p>Results</p> <p>Fifty-nine English-speaking participants evaluated and confirmed the concept validity of the English adapted version. 28 non-English speaking participants evaluated the Gujarati (N = 13) and Punjabi (N = 15) translated versions of the adapted pamphlets. All participants found the pamphlets acceptable and felt they had improved their understanding of hypertension.</p> <p>Conclusions</p> <p>Involving the target community to identify health issues as well as help to create culturally, language and literacy sensitive health education materials ensures resources are highly acceptable to that community. Minor changes to the materials will be needed prior to formal testing of hypertension knowledge and health decision-making on a larger scale within this at risk community.</p

A Transient “Changing-look” Active Galactic Nucleus Resolved on Month Timescales from First-year Sloan Digital Sky Survey V Data

We report the discovery of a new “changing-look” active galactic nucleus (CLAGN) event, in the quasar SDSS J162829.17+432948.5 at z = 0.2603, identified through repeat spectroscopy from the fifth Sloan Digital Sky Survey (SDSS-V). Optical photometry taken during 2020-2021 shows a dramatic dimming of Δg ≈ 1 mag, followed by a rapid recovery on a timescale of several months, with the ≲2 month period of rebrightening captured in new SDSS-V and Las Cumbres Observatory spectroscopy. This is one of the fastest CLAGN transitions observed to date. Archival observations suggest that the object experienced a much more gradual dimming over the period of 2011-2013. Our spectroscopy shows that the photometric changes were accompanied by dramatic variations in the quasar-like continuum and broad-line emission. The excellent agreement between the pre- and postdip photometric and spectroscopic appearances of the source, as well as the fact that the dimmest spectra can be reproduced by applying a single extinction law to the brighter spectral states, favor a variable line-of-sight obscuration as the driver of the observed transitions. Such an interpretation faces several theoretical challenges, and thus an alternative accretion-driven scenario cannot be excluded. The recent events observed in this quasar highlight the importance of spectroscopic monitoring of large active galactic nucleus samples on weeks-to-months timescales, which the SDSS-V is designed to achieve

A Transient "Changing-look'' Active Galactic Nucleus Resolved on Month Timescales from First-year Sloan Digital Sky Survey V Data

We report the discovery of a new ``changing-look'' active galactic nucleus (CLAGN) event, in the quasar SDSS J162829.17+432948.5 at z=0.2603, identified through repeat spectroscopy from the fifth Sloan Digital Sky Survey (SDSS-V). Optical photometry taken during 2020--2021 shows a dramatic dimming of ${\Delta}$g${\approx}$1 mag, followed by a rapid recovery on a timescale of several months, with the ${\lesssim}$2 month period of rebrightening captured in new SDSS-V and Las Cumbres Observatory spectroscopy. This is one of the fastest CLAGN transitions observed to date. Archival observations suggest that the object experienced a much more gradual dimming over the period of 2011--2013. Our spectroscopy shows that the photometric changes were accompanied by dramatic variations in the quasar-like continuum and broad-line emission. The excellent agreement between the pre- and postdip photometric and spectroscopic appearances of the source, as well as the fact that the dimmest spectra can be reproduced by applying a single extinction law to the brighter spectral states, favor a variable line-of-sight obscuration as the driver of the observed transitions. Such an interpretation faces several theoretical challenges, and thus an alternative accretion-driven scenario cannot be excluded. The recent events observed in this quasar highlight the importance of spectroscopic monitoring of large active galactic nucleus samples on weeks-to-months timescales, which the SDSS-V is designed to achieve.Comment: Published in ApJ