Morfología y filogenia del rDNA de una subespecie mediterránea de Coolia Monotis (Dinophyceae) de Grecia

Sequences of LSU and SSU ribosomal RNA genes and phylogeny have not been widely investigated for the dinoflagellate Coolia monotis Meunier, and no information is available on the small and large rDNA subunits of Mediterranean strains. A strain isolated from the Thermaikos Gulf in northern Greece was identified as C. monotis—a new record for the Greek algal flora—using thecal morphology by light, epifluorescence and scanning electron microscopy. The small subunit and partial (D1/D2) large subunit sequences were analyzed and compared to other strains of C. monotis and dinoflagellates from various regions. Thecal architecture showed that the Greek strain of C. monotis was phenotypically similar, but not identical, to other strains reported in literature. The partial LSU sequence (700 bp) was found to vary by 113 bp positions (16%) from the C. monotis strain from New Zealand, whereas the SSU (1757 bp) had 15 bp differences (0.85%) from the strain from Norway. Phylogenetic tree construction showed that the Greek strain fell within the Coolia clade and had a close relationship with the families Ostreopsidaceae and Goniodomaceae of the order Gonyaulacales. Preliminary findings suggest the existence of different genotype strains of C. monotis with large intraspecific genetic variability and minimal morphological differentiation (similar phenotypes). Certain ecological and evolutionary implications of these findings are discussed.Las secuencias de los genes del RNA de las subunidades ribosomales grandes y pequeñas (LSU y SSU, respectivamente) y la filogenia del dinoflagelado Coolia monotis Meunier han sido poco investigadas, y no hay información disponible sobre los genes LSU y SSU de subespecies mediterráneas. Una subespecie aislada del golfo de Thermaikos en el norte de Grecia fue identificada como C. monotis –una nueva aportación a la flora algal griega– por medio de la morfología de la teca observada a través de microscopía óptica, de epifluorescia y electrónica. Las secuencias correspondientes a la subunidad pequeña y a la parte (D1/D2) de la subunidad grande fueron analizadas y comparadas a las de otras subespecies de C. monotis y otras especies de dinoflagelados de diversas regiones. La arquitectura de la teca mostró que la subespecie griega de C. monotis era fenotípicamente similar, pero no idéntica, a otras subespecies registradas en la literatura. Se encontró que la secuencia parcial de la LSU (700 pares de bases o bp) difería de la de C. monotis de Nueva Zelanda en las posiciones de 113 bp (16%), mientras que la SSU (1757 bp) se diferenciaba en 15 bp (0.85%) de la subespecie de Noruega. La construcción del árbol filogenetico demostró que la subespecie griega se situaba dentro de la rama de Coolia y presentaba una relación cercana con las familias Ostreopsidaceae y Goniodomaceae del orden Gonyaulacales. Resultados preliminares sugieren la existencia de diversos genotipos de la subespecie de C. monotis con una importante variabilidad genética intraespecífica y una mínima diferenciación morfológica (fenotipos similares). Se comentan diversas implicaciones ecológicas y evolutivas de estos resultados

Hormonal responses to cholinergic input are different in humans with and without type 2 diabetes mellitus

<div><p>Peripheral muscarinic acetylcholine receptors regulate insulin and glucagon release in rodents but their importance for similar roles in humans is unclear. Bethanechol, an acetylcholine analogue that does not cross the blood-brain barrier, was used to examine the role of peripheral muscarinic signaling on glucose homeostasis in humans with normal glucose tolerance (NGT; n = 10), impaired glucose tolerance (IGT; n = 11), and type 2 diabetes mellitus (T2DM; n = 9). Subjects received four liquid meal tolerance tests, each with a different dose of oral bethanechol (0, 50, 100, or 150 mg) given 60 min before a meal containing acetaminophen. Plasma pancreatic polypeptide (PP), glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), glucose, glucagon, C-peptide, and acetaminophen concentrations were measured. Insulin secretion rates (ISRs) were calculated from C-peptide levels. Acetaminophen and PP concentrations were surrogate markers for gastric emptying and cholinergic input to islets. The 150 mg dose of bethanechol increased the PP response 2-fold only in the IGT group, amplified GLP-1 release in the IGT and T2DM groups, and augmented the GIP response only in the NGT group. However, bethanechol did not alter ISRs or plasma glucose, glucagon, or acetaminophen concentrations in any group. Prior studies showed infusion of xenin-25, an intestinal peptide, delays gastric emptying and reduces GLP-1 release but not ISRs when normalized to plasma glucose levels. Analysis of archived plasma samples from this study showed xenin-25 amplified postprandial PP responses ~4-fold in subjects with NGT, IGT, and T2DM. Thus, increasing postprandial cholinergic input to islets augments insulin secretion in mice but not humans.</p><p><b><i>Trial Registration</i>:</b> ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01434901?term=NCT01434901&rank=1" target="_blank">NCT01434901</a></p></div

Efficiency of Manual Scanning in Recovering Rare Cellular Events Identified by Fluorescence In Situ Hybridization: Simulation of the Detection of Fetal Cells in Maternal Blood

Fluorescence in situ hybridization (FISH) and manual scanning is a widely used strategy for retrieving rare cellular events such as fetal cells in maternal blood. In order to determine the efficiency of these techniques in detection of rare cells, slides of XX cells with predefined numbers (1–10) of XY cells were prepared. Following FISH hybridization, the slides were scanned blindly for the presence of XY cells by different observers. The average detection efficiency was 84% (125/148). Evaluation of probe hybridization in the missed events showed that 9% (2/23) were not hybridized, 17% (4/23) were poorly hybridized, while the hybridization was adequate for the remaining 74% (17/23). In conclusion, manual scanning is a relatively efficient method to recover rare cellular events, but about 16% of the events are missed; therefore, the number of fetal cells per unit volume of maternal blood has probably been underestimated when using manual scanning

Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun.

After nerve injury, myelin and Remak Schwann cells reprogram to repair cells specialized for regeneration. Normally providing strong regenerative support, these cells fail in aging animals, and during chronic denervation that results from slow axon growth. This impairs axonal regeneration and causes significant clinical problems. In mice, we find that repair cells express reduced c-Jun protein as regenerative support provided by these cells declines during aging and chronic denervation. In both cases, genetically restoring Schwann cell c-Jun levels restores regeneration to control levels. We identify potential gene candidates mediating this effect and implicate Shh in the control of Schwann cell c-Jun levels. This establishes that a common mechanism, reduced c-Jun in Schwann cells, regulates success and failure of nerve repair both during aging and chronic denervation. This provides a molecular framework for addressing important clinical problems, suggesting molecular pathways that can be targeted to promote repair in the PNS

CXCL17 is an allosteric inhibitor of CXCR4 through a mechanism of action involving glycosaminoglycans

CXCL17 is a chemokine principally expressed by mucosal tissues, where it facilitates chemotaxis of monocytes, dendritic cells, and macrophages and has antimicrobial properties. CXCL17 is also implicated in the pathology of inflammatory disorders and progression of several cancers, and its expression is increased during viral infections of the lung. However, the exact role of CXCL17 in health and disease requires further investigation, and there is a need for confirmed molecular targets mediating CXCL17 functional responses. Using a range of bioluminescence resonance energy transfer (BRET)–based assays, here we demonstrated that CXCL17 inhibited CXCR4-mediated signaling and ligand binding. Moreover, CXCL17 interacted with neuropillin-1, a VEGFR2 coreceptor. In addition, we found that CXCL17 only inhibited CXCR4 ligand binding in intact cells and demonstrated that this effect was mimicked by known glycosaminoglycan binders, surfen and protamine sulfate. Disruption of putative GAG binding domains in CXCL17 prevented CXCR4 binding. This indicated that CXCL17 inhibited CXCR4 by a mechanism of action that potentially required the presence of a glycosaminoglycan-containing accessory protein. Together, our results revealed that CXCL17 is an endogenous inhibitor of CXCR4 and represents the next step in our understanding of the function of CXCL17 and regulation of CXCR4 signaling

Radio analysis of SN2004C reveals an unusual CSM density profile as a harbinger of core collapse

We present extensive multifrequency Karl G. Jansky Very Large Array (VLA) and Very Long Baseline Array (VLBA) observations of the radio-bright supernova (SN) IIb SN 2004C that span ∼40–2793 days post-explosion. We interpret the temporal evolution of the radio spectral energy distribution in the context of synchrotron self-absorbed emission from the explosion's forward shock as it expands in the circumstellar medium (CSM) previously sculpted by the mass-loss history of the stellar progenitor. VLBA observations and modeling of the VLA data point to a blastwave with average velocity ∼0.06 c that carries an energy of ≈1049 erg. Our modeling further reveals a flat CSM density profile ρCSM ∝ R−0.03±0.22 up to a break radius Rbr ≈ (1.96 ± 0.10) × 1016 cm, with a steep density gradient following ρCSM ∝ R−2.3±0.5 at larger radii. We infer that the flat part of the density profile corresponds to a CSM shell with mass ∼0.021 M☉, and that the progenitor's effective mass-loss rate varied with time over the range (50–500) × 10−5 M☉ yr−1 for an adopted wind velocity vw = 1000 km s−1 and shock microphysical parameters epsilone = 0.1, epsilonB = 0.01. These results add to the mounting observational evidence for departures from the traditional single-wind mass-loss scenarios in evolved, massive stars in the centuries leading up to core collapse. Potentially viable scenarios include mass loss powered by gravity waves and/or interaction with a binary companion

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Revealing the progenitor of SN 2021zby through analysis of the TESSTESS shock-cooling light curve

We present early observations and analysis of the double-peaked Type IIb supernova (SN IIb) 2021zby. $TESS$ captured the prominent early shock cooling peak of SN 2021zby within the first $\sim$10 days after explosion with a 30-minute cadence. We present optical and near-infrared spectral series of SN 2021zby, including three spectra during the shock cooling phase. Using a multi-band model fit, we find that the inferred properties of its progenitor are consistent with a red supergiant or yellow supergiant, with an envelope mass of $\sim$0.3-3.0 M$_\odot$ and an envelope radius of $\sim$50-350$R_\odot$. These inferred progenitor properties are similar to those of other SNe IIb with double-peak feature, such as SNe 1993J, 2011dh, 2016gkg and 2017jgh. This study further validates the importance of the high cadence and early coverage in resolving the shape of the shock cooling light curve, while the multi-band observations, especially UV, is also necessary to fully constrain the progenitor properties.Comment: 12 pages, 5 figures, 2 tables, submitted to ApJ

Evidence for Extended Hydrogen-Poor CSM in the Three-Peaked Light Curve of Stripped Envelope Ib Supernova

We present multi-band ATLAS photometry for SN 2019tsf, a stripped-envelope Type Ib supernova (SESN). The SN shows a triple-peaked light curve and a late (re-)brightening, making it unique among stripped-envelope systems. The re-brightening observations represent the latest photometric measurements of a multi-peaked Type Ib SN to date. As late-time photometry and spectroscopy suggest no hydrogen, the potential circumstellar material (CSM) must be H-poor. Moreover, late (>150 days) spectra show no signs of narrow emission lines, further disfavouring CSM interaction. On the contrary, an extended CSM structure is seen through a follow-up radio campaign with Karl G. Jansky Very Large Array (VLA), indicating a source of bright optically thick radio emission at late times, which is highly unusual among H-poor SESNe. We attribute this phenomenology to an interaction of the supernova ejecta with spherically-asymmetric CSM, potentially disk-like, and we present several models that can potentially explain the origin of this rare Type Ib supernova. The warped disc model paints a novel picture, where the tertiary companion perturbs the progenitors CSM, that can explain the multi-peaked light curves of SNe, and here we apply it to SN 2019tsf. This SN 2019tsf is likely a member of a new sub-class of Type Ib SNe and among the recently discovered class of SNe that undergo mass transfer at the moment of explosionComment: 23 pages, Comments are welcome, Submitted to Ap