Identification of the protein kinases Pyk3 and Phg2 as regulators of the STATc-mediated response to hyperosmolarity

Cellular adaptation to changes in environmental osmolarity is crucial for cell survival. In Dictyostelium, STATc is a key regulator of the transcriptional response to hyperosmotic stress. Its phosphorylation and consequent activation is controlled by two signaling branches, one cGMP- and the other Ca(2+)-dependent, of which many signaling components have yet to be identified. The STATc stress signalling pathway feeds back on itself by upregulating the expression of STATc and STATc-regulated genes. Based on microarray studies we chose two tyrosine-kinase like proteins, Pyk3 and Phg2, as possible modulators of STATc phosphorylation and generated single and double knock-out mutants to them. Transcriptional regulation of STATc and STATc dependent genes was disturbed in pyk3(-), phg2(-), and pyk3(-)/phg2(-) cells. The absence of Pyk3 and/or Phg2 resulted in diminished or completely abolished increased transcription of STATc dependent genes in response to sorbitol, 8-Br-cGMP and the Ca(2+) liberator BHQ. Also, phospho-STATc levels were significantly reduced in pyk3(-) and phg2(-) cells and even further decreased in pyk3(-)/phg2(-) cells. The reduced phosphorylation was mirrored by a significant delay in nuclear translocation of GFP-STATc. The protein tyrosine phosphatase 3 (PTP3), which dephosphorylates and inhibits STATc, is inhibited by stress-induced phosphorylation on S448 and S747. Use of phosphoserine specific antibodies showed that Phg2 but not Pyk3 is involved in the phosphorylation of PTP3 on S747. In pull-down assays Phg2 and PTP3 interact directly, suggesting that Phg2 phosphorylates PTP3 on S747 in vivo. Phosphorylation of S448 was unchanged in phg2(-) cells. We show that Phg2 and an, as yet unknown, S448 protein kinase are responsible for PTP3 phosphorylation and hence its inhibition, and that Pyk3 is involved in the regulation of STATc by either directly or indirectly activating it. Our results add further complexities to the regulation of STATc, which presumably ensure its optimal activation in response to different environmental cues

Individual-level socioeconomic status is associated with worse asthma morbidity in patients with asthma

<p>Abstract</p> <p>Background</p> <p>Low socioeconomic status (SES) has been linked to higher morbidity in patients with chronic diseases, but may be particularly relevant to asthma, as asthmatics of lower SES may have higher exposures to indoor (e.g., cockroaches, tobacco smoke) and outdoor (e.g., urban pollution) allergens, thus increasing risk for exacerbations.</p> <p>Methods</p> <p>This study assessed associations between adult SES (measured according to educational level) and asthma morbidity, including asthma control; asthma-related emergency health service use; asthma self-efficacy, and asthma-related quality of life, in a Canadian cohort of 781 adult asthmatics. All patients underwent a sociodemographic and medical history interview and pulmonary function testing on the day of their asthma clinic visit, and completed a battery of questionnaires (Asthma Control Questionnaire, Asthma Quality of Life Questionnaire, and Asthma Self-Efficacy Scale). General Linear Models assessed associations between SES and each morbidity measure.</p> <p>Results</p> <p>Lower SES was associated with worse asthma control (F = 11.63, p < .001), greater emergency health service use (F = 5.09, p = .024), and worse asthma self-efficacy (F = 12.04, p < .01), independent of covariates. Logistic regression analyses revealed that patients with <12 years of education were 55% more likely to report an asthma-related emergency health service visit in the last year (OR = 1.55, 95%CI = 1.05-2.27). Lower SES was not related to worse asthma-related quality of life.</p> <p>Conclusions</p> <p>Results suggest that lower SES (measured according to education level), is associated with several indices of worse asthma morbidity, particularly worse asthma control, in adult asthmatics independent of disease severity. Results are consistent with previous studies linking lower SES to worse asthma in children, and add asthma to the list of chronic diseases affected by individual-level SES.</p

High Throughput, Multiplexed Pathogen Detection Authenticates Plague Waves in Medieval Venice, Italy

Background: Historical records suggest that multiple burial sites from the 14th-16(th) centuries in Venice, Italy, were used during the Black Death and subsequent plague epidemics.Methodology/Principal Findings: High throughput, multiplexed real-time PCR detected DNA of seven highly transmissible pathogens in 173 dental pulp specimens collected from 46 graves. Bartonella quintana DNA was identified in five (2.9%) samples, including three from the 16th century and two from the 15th century, and Yersinia pestis DNA was detected in three (1.7%) samples, including two from the 14th century and one from the 16th century. Partial glpD gene sequencing indicated that the detected Y. pestis was the Orientalis biotype.Conclusions: These data document for the first time successive plague epidemics in the medieval European city where quarantine was first instituted in the 14th century

Drama, performance and touch in the medieval convent and beyond

In this analysis we explore the sensory performances of the performer, rather than the spectator, in medieval convent drama, particularly the tactile experiences of clothing, props, wigs, and beards worn by female performers presenting male and female characters

Genome-wide identification of NBS-encoding resistance genes in Brassica rapa

Nucleotide-binding site (NBS)-encoding resistance genes are key plant disease-resistance genes and are abundant in plant genomes, comprising up to 2% of all genes. The availability of genome sequences from several plant models enables the identification and cloning of NBS-encoding genes from closely related species based on a comparative genomics approach. In this study, we used the genome sequence of Brassica rapa to identify NBS-encoding genes in the Brassica genome. We identified 92 non-redundant NBS-encoding genes [30 CC-NBS-LRR (CNL) and 62 TIR-NBS-LRR (TNL) genes] in approximately 100 Mbp of B. rapa euchromatic genome sequence. Despite the fact that B. rapa has a significantly larger genome than Arabidopsis thaliana due to a recent whole genome triplication event after speciation, B. rapa contains relatively small number of NBS-encoding genes compared to A. thaliana, presumably because of deletion of redundant genes related to genome diploidization. Phylogenetic and evolutionary analyses suggest that relatively higher relaxation of selective constraints on the TNL group after the old duplication event resulted in greater accumulation of TNLs than CNLs in both Arabidopsis and Brassica genomes. Recent tandem duplication and ectopic deletion are likely to have played a role in the generation of novel Brassica lineage-specific resistance genes

PHANGS-JWST First Results: A Combined HST and JWST Analysis of the Nuclear Star Cluster in NGC 628

We combine archival Hubble Space Telescope and new James Webb Space Telescope imaging data covering the ultraviolet to mid-infrared regime to morphologically analyze the nuclear star cluster (NSC) of NGC 628, a grand-design spiral galaxy. The cluster is located in a 200 pc × 400 pc cavity lacking both dust and gas. We find roughly constant values for the effective radius (r eff ∼ 5 pc) and ellipticity (ε ∼ 0.05), while the Sérsic index (n) and position angle (PA) drop from n ∼ 3 to ∼2 and PA ∼ 130° to 90°, respectively. In the mid-infrared, r eff ∼ 12 pc, ε ∼ 0.4, and n ∼ 1-1.5, with the same PA ∼ 90°. The NSC has a stellar mass of log 10 ( M ⋆ nsc / M ⊙ ) = 7.06 ± 0.31 , as derived through B − V, confirmed when using multiwavelength data, and in agreement with the literature value. Fitting the spectral energy distribution (SED), excluding the mid-infrared data, yields a main stellar population age of (8 ± 3) Gyr with a metallicity of Z = 0.012 ± 0.006. There is no indication of any significant star formation over the last few gigayears. Whether gas and dust were dynamically kept out or evacuated from the central cavity remains unclear. The best fit suggests an excess of flux in the mid-infrared bands, with further indications that the center of the mid-infrared structure is displaced with respect to the optical center of the NSC. We discuss five potential scenarios, none of them fully explaining both the observed photometry and structure

PHANGS-JWST First Results: Interstellar Medium Structure on the Turbulent Jeans Scale in Four Disk Galaxies Observed by JWST and the Atacama Large Millimeter/submillimeter Array

JWST/Mid-Infrared Instrument imaging of the nearby galaxies IC 5332, NGC 628, NGC 1365, and NGC 7496 from PHANGS reveals a richness of gas structures that in each case form a quasi-regular network of interconnected filaments, shells, and voids. We examine whether this multiscale network of structure is consistent with the fragmentation of the gas disk through gravitational instability. We use FilFinder to detect the web of filamentary features in each galaxy and determine their characteristic radial and azimuthal spacings. These spacings are then compared to estimates of the most Toomre-unstable length (a few kiloparsecs), the turbulent Jeans length (a few hundred parsecs), and the disk scale height (tens of parsecs) reconstructed using PHANGS-Atacama Large Millimeter/submillimeter Array observations of the molecular gas as a dynamical tracer. Our analysis of the four galaxies targeted in this work indicates that Jeans-scale structure is pervasive. Future work will be essential for determining how the structure observed in gas disks impacts not only the rate and location of star formation but also how stellar feedback interacts positively or negatively with the surrounding multiphase gas reservoir. © 2023

Variable Carbon Catabolism among Salmonella enterica Serovar Typhi Isolates

BACKGROUND: Salmonella enterica serovar Typhi (S. Typhi) is strictly a human intracellular pathogen. It causes acute systemic (typhoid fever) and chronic infections that result in long-term asymptomatic human carriage. S. Typhi displays diverse disease manifestations in human infection and exhibits high clonality. The principal factors underlying the unique lifestyle of S. Typhi in its human host during acute and chronic infections remain largely unknown and are therefore the main objective of this study. METHODOLOGY/PRINCIPAL FINDINGS: To obtain insight into the intracellular lifestyle of S. Typhi, a high-throughput phenotypic microarray was employed to characterise the catabolic capacity of 190 carbon sources in S. Typhi strains. The success of this study lies in the carefully selected library of S. Typhi strains, including strains from two geographically distinct areas of typhoid endemicity, an asymptomatic human carrier, clinical stools and blood samples and sewage-contaminated rivers. An extremely low carbon catabolic capacity (27% of 190 carbon substrates) was observed among the strains. The carbon catabolic profiles appeared to suggest that S. Typhi strains survived well on carbon subtrates that are found abundantly in the human body but not in others. The strains could not utilise plant-associated carbon substrates. In addition, α-glycerolphosphate, glycerol, L-serine, pyruvate and lactate served as better carbon sources to monosaccharides in the S. Typhi strains tested. CONCLUSION: The carbon catabolic profiles suggest that S. Typhi could survive and persist well in the nutrient depleted metabolic niches in the human host but not in the environment outside of the host. These findings serve as caveats for future studies to understand how carbon catabolism relates to the pathogenesis and transmission of this pathogen

PHANGS-JWST First Results: Spurring on Star Formation: JWST Reveals Localized Star Formation in a Spiral Arm Spur of NGC 628

We combine JWST observations with Atacama Large Millimeter/submillimeter Array CO and Very Large Telescope MUSE Hα data to examine off-spiral arm star formation in the face-on, grand-design spiral galaxy NGC 628. We focus on the northern spiral arm, around a galactocentric radius of 3-4 kpc, and study two spurs. These form an interesting contrast, as one is CO-rich and one CO-poor, and they have a maximum azimuthal offset in MIRI 21 μm and MUSE Hα of around 40° (CO-rich) and 55° (CO-poor) from the spiral arm. The star formation rate is higher in the regions of the spurs near spiral arms, but the star formation efficiency appears relatively constant. Given the spiral pattern speed and rotation curve of this galaxy and assuming material exiting the arms undergoes purely circular motion, these offsets would be reached in 100-150 Myr, significantly longer than the 21 μm and Hα star formation timescales (both &lt; 10 Myr). The invariance of the star formation efficiency in the spurs versus the spiral arms indicates massive star formation is not only triggered in spiral arms, and cannot simply occur in the arms and then drift away from the wave pattern. These early JWST results show that in situ star formation likely occurs in the spurs, and that the observed young stars are not simply the “leftovers” of stellar birth in the spiral arms. The excellent physical resolution and sensitivity that JWST can attain in nearby galaxies will well resolve individual star-forming regions and help us to better understand the earliest phases of star formation

Differential Detection of Genetic Loci Underlying Stem and Root Lignin Content in Populus

In this study, we established a comprehensive genetic map with a large number of progeny from a three-generation hybrid Populus intercross, and phenotyped the lignin content, S/G ratio and 28 cell wall subcomponents both in stems and roots for the mapping individuals. Phenotypic analysis revealed that lignin content and syringyl-to-guaiacyl (S/G) ratio using pyrolysis molecular beam mass spectroscopy (pyMBMS) varied among mapping individuals. Phenotypic analysis revealed that stem lignin content is significantly higher than that in root and the quantified traits can be classified into four distinct groups, with strong correlations observed among components within organs. Altogether, 179 coordinating QTLs were detected, and they were co-localized into 49 genetic loci, 27 of which appear to be pleiotropic. Many of the detected genetic loci were detected differentially in stem and root. This is the first report of separate genetic loci controlling cell wall phenotypes above and below ground. These results suggest that it may be possible to modify lignin content and composition via breed and/or engineer as a means of simultaneously improving Populus for cellulosic ethanol production and carbon sequestration