Immunocytochemical localization and immunochemical characterization of an insulin-related peptide in the pancreas of the urodele amphibian,Ambystoma mexicanum

Summary The pancreas of the axolotl, Ambystoma mexicanum, was investigated by immunocytochemical methods for the presence of immunoreactivity to a number of antisera raised against mammalian insulins. All anti-insulin antisera tested revealed substantial amounts of reaction products confined solely to the aldehyde-fuchsinophilic B cells of the endocrine pancreas. The reactive cell population was detected by use of one polyclonal antiserum against bovine insulin and eight different monoclonal antibodies against insulins from various mammalian species. Six of these antibody clones have known specificity to sub-regions of the insulin molecule. Additionally, fractions of an ethanol-HCl extract of pancreatic tissue from Ambystoma was studied in both conventional dot-blot tests by means of the same panel of antibodies and a two-site sandwich time-resolved immunofluorometric assay for human insulin involving two of the monoclonal antibodies. These experiments support the immunocytochemical observations by demonstrating the existence of an insulin-related peptide with a great deal of structural resemblance to mammalian insulins and displaying antigenic determinants in common at least with the amino acid residues A_8–10 and B_26–30. In conclusion, we interpret the findings as indicating that the immunocytochemically revealed tissue bound antigen in the Ambystoma pancreatic B-cells may be a peptide related to human insulin.Supported in part by SNF grant 11-5082 (G.N.H.). The authors are indebted to Dr. P. Rosenkilde for the gift of the Ambystoma material     

The effects of azadirachtin A on the morphology of the ring complex of Lucilia cuprina (Wied) larvae (Diptera: Insecta)

This study investigated the effect of azadirachtin A (AZA) on the ultrastructure of the endocrine glands (the prothoracic gland, the corpus allatum, and the corpus cardiacum) responsible for controlling moulting and ecdysis in Lucilia cuprina larvae. All constituent endocrine glands within the ring complex exhibited ultrastructural change after exposure of larvae to AZ A in the diet. The effects on the nucleus were the most noticeable and included: (1) crenulation of nuclear shape, (2) clumping of heterochromatin, and (3) pyknosis. The degenerative changes to the nuclei appeared to precede changes within the cytoplasm. It was concluded that the degeneration of all three endocrine glands within the ring complex would contribute to a generalised disruption of neuroendocrine function.     

Iodoacetate Produces Striatal Excitotoxic Lesions

Abstract: Impairment of energy production may play a role in the pathogenesis of Huntington's disease (HD). It was recently shown that huntingtin can bind to and possibly inhibit the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). We found that intrastriatal administration of the GAPDH inhibitor iodoacetate produces striatal lesions that are significantly attenuated by removal of the corticostriatal glutamatergic input, consistent with an excitotoxic mechanism. The lesions are accompanied by increased production of hydroxyl free radicals as assessed by conversion of salicylate to 2,3- and 2,5-dihydroxybenzoic acid. In vivo magnetic resonance imaging showed lesions on T ₂-weighted scans, but there was only a small increase in lactate content. These results show that inhibition of GAPDH produces striatal lesions in vivo and suggest that inhibition of GAPDH could contribute to neuronal degeneration in HD.     

Show Me Your Rump Hair and I Will Tell You What You Ate – The Dietary History of Muskoxen (Ovibos moschatus) Revealed by Sequential Stable Isotope Analysis of Guard Hairs

The nutritional state of animals is tightly linked to the ambient environment, and for northern ungulates the state strongly influences vital population demographics, such as pregnancy rates. Continuously growing tissues, such as hair, can be viewed as dietary records of animals over longer temporal scales. Using sequential data on nitrogen stable isotopes (δ¹⁵N) in muskox guard hairs from ten individuals in high arctic Northeast Greenland, we were able to reconstruct the dietary history of muskoxen over approximately 2.5 years with a high temporal resolution of app. 9 days. The dietary chronology included almost three full summer and winter periods. The diet showed strong intra- and inter-annual seasonality, and was significantly linked to changes in local environmental conditions (temperature and snow depth). The summer diets were highly similar across years, reflecting a graminoid-dominated diet. In contrast, winter diets were markedly different between years, a pattern apparently linked to snow conditions. Snow-rich winters had markedly higher δ¹⁵N values than snow-poor winters, indicating that muskoxen had limited access to forage, and relied more heavily on their body stores. Due to the close link between body stores and calf production in northern ungulates, the dietary winter signals could eventually serve as an indicator of calf production the following spring. Our study opens the field for further studies and longer chronologies to test such links. The method of sequential stable isotope analysis of guard hairs thus constitutes a promising candidate for population-level monitoring of animals in remote, arctic areas.     

Morphology and evolution of the nervous system in Gnathostomulida (Gnathifera,Spiralia)

Within Spiralia, Gnathifera may represent the deepest branching lineage comprising the jaw worms Gnathostomulida and their sister group Micrognathozoa + Syndermata. Yet, very few nervous system studies have been conducted on this lineage of microscopic, jaw-bearing worms, limiting our understanding of the evolution of this organ system in Spiralia. The nervous system of representatives from all major groups of Gnathostomulida was here mapped using confocal laser scanning microscopy and immunohistochemistry. Their intra-epidermal, unsegmented nervous systems comprise an anterior brain and three to five ventral and two to four dorsal longitudinal nerves, connected by few transverse commissures. Neurites of the stomatogastric nervous system were found lining the pharynx and connecting to a prominent buccal ganglion. Supposedly, sensory ciliated cells in the pharynx and the gut were documented for the first time. Based on these morphological results, primary homologies of neural structures in Gnathostomulida and other Gnathifera were hypothesized and thereafter tested using parsimony. This first neurophylogeny of Gnathostomulida resulted in a topology congruent with molecular data, supporting the monophyly of Bursovaginoidea, Conophoralia, and Scleroperalia. From this topology, the evolution of the gnathostomulid nervous system was reconstructed. It suggests a specialization and diversification of cords and serotonin-like immunoreactive cell patterns from a plesiomorphic neuroarchitecture of three unsegmented nerve cords and a compact anterior brain and buccal ganglion. These plesiomorphic states resemble the nervous system of Micrognathozoa, and possibly the ancestral states of Spiralia.     

Phylogeny and biogeography of the scaleless scale worm Pisione (Sigalionidae,Annelida)

Pisione is a scaleless group of small scale worms inhabiting sandy bottoms in shallow marine waters. This group was once considered rare, but now 45 described species can be characterized, among others, by their paired, segmental copulatory organs (one to multiple external pairs), which display a complexity of various accessory structures. The evolutionary significance of these unique organs was suggested in the late 1960s, but has been heavily debated since the late 1990s and remains controversial. In the present paper, we study the internal relationships within Pisione, employing combined phylogenetic analyses of both molecular and morphological data from 16 terminals of Pisione, as well as two terminals of Pisionidens, and eight additional scale worms as outgroups. Our taxon sampling covers all geographical areas where the genus has been reported, as well as most of their morphological and copulatory variability, including representatives of the “africana,” “remota,” “crassa,” and “papuensis” groups, established previously by Yamanishi. We hereby provide a first insight into the relationships of the genus, testing previously proposed hypotheses on the evolutionary significance of male copulatory structures within Pisione, while attempting to understand patterns of distribution. The phylogenetic analyses using maximum likelihood and Bayesian methods consistently recovered two large clades spanning the East Atlantic (including the Mediterranean) and the Indo‐Pacific–West Atlantic, respectively. Character optimization on our trees revealed a high degree of homoplasy in both non‐reproductive and sexual characters of Pisione, with buccal acicula found to be the sole apomorphy among the morphological features assessed herein, with none defining the biogeographical subclades within. Overall, our comparative analyses highlight the high degree of morphological variation in this widely distributed genus, rejecting previous assertions of an increasing number and complexity of copulatory structures across the genus.     

Vaccine effectiveness against SARS-CoV-2 infection,hospitalization, and death when combining a first dose ChAdOx1 vaccine with a subsequent mRNA vaccine in Denmark: A nationwide population-based cohort study

BackgroundThe recommendations in several countries to stop using the ChAdOx1 vaccine has led to vaccine programs combining different Coronavirus Disease 2019 (COVID-19) vaccine types, which necessitates knowledge on vaccine effectiveness (VE) of heterologous vaccine schedules. The aim of this Danish nationwide population-based cohort study was therefore to estimate the VE against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and COVID-19–related hospitalization and death following the first dose of the ChAdOx1 vaccine and the combination of the ChAdOx1/mRNA vaccines.Methods and findingsAll individuals alive in or immigrating to Denmark from 9 February 2021 to 23 June 2021 were identified in the Danish Civil Registration System. Information on exposure, outcomes, and covariates was obtained from Danish national registries. Poisson and Cox regression models were used to calculate crude and adjusted VE, respectively, along with 95% confidence intervals (CIs) against SARS-CoV-2 infection and COVID-19–related hospitalization or death comparing vaccinated versus unvaccinated individuals. The VE estimates were adjusted for calendar time as underlying time and for sex, age, comorbidity, country of origin, and hospital admission. The analyses included 5,542,079 individuals (97.6% of the total Danish population). A total of 144,360 individuals were vaccinated with the ChAdOx1 vaccine as the first dose, and of these, 136,551 individuals received an mRNA vaccine as the second dose. A total of 1,691,464 person-years and 83,034 SARS-CoV-2 infections were included. The individuals vaccinated with the first dose of the ChAdOx1 vaccine dose had a median age of 45 years. The study population was characterized by an equal distribution of males and females; 6.7% and 9.2% originated from high-income and other countries, respectively. The VE against SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine was 88% (95% CI: 83; 92) 14 days after the second dose and onwards. There were no COVID-19–related hospitalizations or deaths among the individuals vaccinated with the combined vaccine schedule during the study period. Study limitations including unmeasured confounders such as risk behavior and increasing overall vaccine coverage in the general population creating herd immunity are important to take into consideration when interpreting the results.ConclusionsIn this study, we observed a large reduction in the risk of SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine, compared with unvaccinated individuals.

Mie Agermose Gram and co-workers study the effectiveness of heterologous SARS-CoV-2 vaccine combinations in the Danish population.     

Differential expression of parvalbumin in neonatal phencyclidine‐treated rats and socially isolated rats

Decreased parvalbumin expression is a hallmark of the pathophysiology of schizophrenia and has been associated with abnormal cognitive processing and decreased network specificity. It is not known whether this decrease is due to reduced expression of the parvalbumin protein or degeneration of parvalbumin‐positive interneurons (PV⁺ interneurons). In this study, we examined PV⁺ expression in two rat models of cognitive dysfunction in schizophrenia: the environmental social isolation (SI) and pharmacological neonatal phencyclidine (neoPCP) models. Using a stereological method, the optical fractionator, we counted neurons, PV⁺ interneurons, and glial cells in the medial prefrontal cortex (mPFC) and hippocampus (HPC). In addition, we quantified the mRNA level of parvalbumin in the mPFC. There was a statistically significant reduction in the number of PV⁺ interneurons (p = 0.021) and glial cells (p = 0.024) in the mPFC of neonatal phencyclidine rats, but not in SI rats. We observed no alterations in the total number of neurons, hippocampal PV⁺ interneurons, parvalbumin mRNA expression or volume of the mPFC or HPC in the two models. Thus, as the total number of neurons remains unchanged following phencyclidine (PCP) treatment, we suggest that the decreased number of counted PV⁺ interneurons represents a reduced parvalbumin protein expression below immunohistochemical detection limit rather than a true cell loss. Furthermore, these results indicate that the effect of neonatal PCP treatment is not limited to neuronal populations.     

Gain of palps within a lineage of ancestrally burrowing annelids (Scalibregmatidae)

Scalibregmatidae is a small annelid family of subsurface deposit feeders in sand or mud, which are generally well adapted to infaunal burrowing. The overall morphology of Scalibregmatidae is very similar, with thick bodies, small parapodia, and no prostomial appendages or short horns. The only exception is members of the genera Axiokebuita and Speleobregma that most frequently inhabit crevices or gravel and possess extensive ventral ciliated palps and globular adhesive pygidium. Character reconstruction using maximum likelihood and Bayesian methods show that ciliated palps and adhesive pygidium are synapomorphies of the Axiokebuita–Speleobregma clade. The most likely transformation series is from horns to ciliated palps, the origin of which correlates with the occurrence of Axiokebuita and Speleobregma in crevices or gravel. The wide spaces among rocks or granules yield high permeability and inertial water flow, preventing deposition of organic matter. Under these flow conditions that differ significantly from those of sand or mud bottom, ciliated palps aid to the collection of suspended particles and an adhesive pygidium provides attachment. With palps being a highly debated character in annelid evolution, it is remarkable that prominent ciliated palps are gained within a lineage of ancestrally nonpalpate annelids, most likely increasing their fitness when colonizing a new environment.