Noggin as a regulator of bone remodelling

Bone Morphogenetic Protein 2 (BMP2) is used in orthopaedic surgery to promote bone healing. The endogenous synthesis of BMP-2 antagonist family members, however, may limit the efficacy of exogenous BMP2. Noggin is one of these inhibitors that blocks the effects of BMP on the differentiation and activation of osteoblast (OB) in vitro and in vivo and inhibits OB-mediated osteoclast (OC) development. Furthermore, Noggin was found to modulate osteoclastogenesis through a direct effect on OC lineage cells. The present study aimed at elucidating the underlying mechanisms of these effects. Direct (conventional culture dishes) and indirect (transwell culture dishes) co-cultures of murine OB/OPC (Osteoclast Progenitor Cells) and cultures of OPC alone were supplemented with combinations of Noggin, BMP2, L51P (engineered, inactive variant of BMP2) and DMH1 (BMP receptor 1 inhibitor). In cultures of OPC, Noggin but not DMH1 caused an increase in the number of OC by a factor of 3 (p< 0.01). This effect could not be reversed by BMP2 and L51P, respectively. In contrast, in co-cultures of OB/OPC, exposure to Noggin attenuated OC development. In direct co-cultures, this inhibitory effect of Noggin was blocked by BMP2 and L51P. In both direct and indirect co-culture systems, exposure to Noggin induced the release of GM-CSF, a potent inhibitor of osteoclastogenesis, by a factor of 6 and 4, respectively (p< 0.01). Treatment of the cultures with αGM-CSF Ab, however, restored OC development in the indirect co-culture system only. The data suggests a previously unknown function of Noggin directly acting pro-differentiation on OC lineage cells independently of BMP signalling. In co-cultures, besides GM-CSF, cell-cell contact between OB and OPC is required for mediation of the maximal inhibitory effects of Noggin on OC development. The nature of potential interaction partners for Noggin, however, remains to be elucidated

Taxonomic shifts in arbuscular mycorrhizal fungal communities with shade and soil nitrogen across conventionally managed and organic coffee agroecosystems

The composition of arbuscular mycorrhizal fungal (AMF) communities should reflect not only responses to host and soil environments, but also differences in functional roles and costs vs. benefits among arbuscular mycorrhizal fungi. The coffee agroecosystem allows exploration of the effects of both light and soil fertility on AMF communities, because of the variation in shade and soil nutrients farmers generate through field management. We used high-throughput ITS2 sequencing to characterize the AMF communities of coffee roots in 25 fields in Costa Rica that ranged from organic management with high shade and no chemical fertilizers to conventionally managed fields with minimal shade and high N fertilization, and examined relationships between AMF communities and soil and shade parameters with partial correlations, NMDS, PERMANOVA, and partial least squares analysis. Gigasporaceae and Acaulosporaceae dominated coffee AMF communities in terms of relative abundance and richness, respectively. Gigasporaceae richness was greatest in conventionally managed fields, while Glomeraceae richness was greatest in organic fields. While total AMF richness and root colonization did not differ between organic and conventionally managed fields, AMF community composition did; these differences were correlated with soil nitrate and shade. OTUs differing in relative abundance between conventionally managed and organic fields segregated into four groups: Gigasporaceae associated with high light and nitrate availability, Acaulosporaceae with high light and low nitrate availability, Acaulosporaceae and a single relative of Rhizophagus fasciculatus with shade and low nitrate availability, and Claroideoglomus/Glomus with conventionally managed fields but uncorrelated with shade and soil variables. The association of closely related taxa with similar shade and light availabilities is consistent with phylogenetic trait conservatism in AM fungi

Contrasting patterns of functional diversity in coffee root fungal communities associated with organic and conventionally managed fields

The structure and function of fungal communities in the coffee rhizosphere are influenced by crop environment. Because coffee can be grown along a management continuum from conventional application of pesticides and fertilizers in full sun to organic management in a shaded understory, we used coffee fields to hold host constant while comparing rhizosphere fungal communities under markedly different environmental conditions with regard to shade and inputs. We characterized the shade and soil environment in 25 fields under conventional, organic, or transitional management in two regions of Costa Rica. We amplified the internal transcribed spacer 2 (ITS2) region of fungal DNA from coffee roots in these fields and characterized the rhizosphere fungal community via high-throughput sequencing. Sequences were assigned to guilds to determine differences in functional diversity and trophic structure among coffee field environments. Organic fields had more shade, a greater richness of shade tree species, and more leaf litter and were less acidic, with lower soil nitrate availability and higher soil copper, calcium, and magnesium availability than conventionally managed fields, although differences between organic and conventionally managed fields in shade and calcium and magnesium availability depended on region. Differences in richness and community composition of rhizosphere fungi between organic and conventionally managed fields were also correlated with shade, soil acidity, and nitrate and copper availability. Trophic structure differed with coffee field management. Saprotrophs, plant pathogens, and mycoparasites were more diverse, and plant pathogens were more abundant, in organic than in conventionally managed fields, while saprotroph-plant pathogens were more abundant in conventionally managed fields. These differences reflected environmental differences and depended on region

A comprehensive microarray-based DNA methylation study of 367 hematological neoplasms

Background: Alterations in the DNA methylation pattern are a hallmark of leukemias and lymphomas. However, most epigenetic studies in hematologic neoplasms (HNs) have focused either on the analysis of few candidate genes or many genes and few HN entities, and comprehensive studies are required. Methodology/Principal Findings: Here, we report for the first time a microarray-based DNA methylation study of 767 genes in 367 HNs diagnosed with 16 of the most representative B-cell (n = 203), T-cell (n = 30), and myeloid (n = 134) neoplasias, as well as 37 samples from different cell types of the hematopoietic system. Using appropriate controls of B-, T-, or myeloid cellular origin, we identified a total of 220 genes hypermethylated in at least one HN entity. In general, promoter hypermethylation was more frequent in lymphoid malignancies than in myeloid malignancies, being germinal center mature B-cell lymphomas as well as B and T precursor lymphoid neoplasias those entities with highest frequency of gene-associated DNA hypermethylation. We also observed a significant correlation between the number of hypermethylated and hypomethylated genes in several mature B-cell neoplasias, but not in precursor B- and T-cell leukemias. Most of the genes becoming hypermethylated contained promoters with high CpG content, and a significant fraction of them are targets of the polycomb repressor complex. Interestingly, T-cell prolymphocytic leukemias show low levels of DNA hypermethylation and a comparatively large number of hypomethylated genes, many of them showing an increased gene expression. Conclusions/Significance: We have characterized the DNA methylation profile of a wide range of different HNs entities. As well as identifying genes showing aberrant DNA methylation in certain HN subtypes, we also detected six genes—DBC1, DIO3, FZD9, HS3ST2, MOS, and MYOD1—that were significantly hypermethylated in B-cell, T-cell, and myeloid malignancies. These might therefore play an important role in the development of different HNs

Pediatric Multisystem Inflammatory Syndrome in Children as a Challenging Problem for Pediatric Surgeons in the COVID 19 Pandemic—A Case Report

The first cases of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection were identified at the end of 2019 and, in the next few months, coronavirus disease (COVID-19) spread throughout the world. Initially, it was believed that this disease mainly affected elderly individuals with comorbidities, in whom respiratory failure often occurs. It was believed that children fell ill from the infection more often, although the course of infection in the vast majority of pediatric cases has been asymptomatic or mildly symptomatic. In April and May 2020, the first report of a rapidly progressing disease, similar to Kawasaki syndrome, was found in children who had been infected with SARS-CoV-2. Shortly thereafter, children with symptoms of pediatric inflammatory multisystem syndrome (PIMS-ST [temporally associated with SARS-CoV-2 infection]) began presenting to pediatric hospitals around the world. The syndrome has a mortality rate of up to 2%. Symptoms of PIMS-TS include those that may suggest the need for surgical treatment (severe abdominal pain with the presence of peritoneal symptoms, ascites, high levels of inflammatory markers, intestinal inflammation, and appendages revealed on ultrasound examination). However, there are few reports addressing surgical cases associated with this condition. The authors present a case involving an 11-year-old boy who was admitted to hospital with severe abdominal pain and underwent surgery for symptoms of peritonitis and was diagnosed with PIMS in the post-operative period. Due to the large number of illnesses caused by SARS-CoV-2 infection in recent months, the diagnosis of PIMS-TS/MISC should be considered in the differential diagnosis of acute abdominal symptoms, especially in atypical courses and interviews indicating exposure to SARS-CoV-2

The Compton Spectrometer and Imager

The Compton Spectrometer and Imager (COSI) is a NASA Small Explorer (SMEX) satellite mission in development with a planned launch in 2027. COSI is a wide-field gamma-ray telescope designed to survey the entire sky at 0.2-5 MeV. It provides imaging, spectroscopy, and polarimetry of astrophysical sources, and its germanium detectors provide excellent energy resolution for emission line measurements. Science goals for COSI include studies of 0.511 MeV emission from antimatter annihilation in the Galaxy, mapping radioactive elements from nucleosynthesis, determining emission mechanisms and source geometries with polarization measurements, and detecting and localizing multimessenger sources. The instantaneous field of view for the germanium detectors is >25% of the sky, and they are surrounded on the sides and bottom by active shields, providing background rejection as well as allowing for detection of gamma-ray bursts and other gamma-ray flares over most of the sky. In the following, we provide an overview of the COSI mission, including the science, the technical design, and the project status.Comment: 8 page

The cosipy library: COSI's high-level analysis software

The Compton Spectrometer and Imager (COSI) is a selected Small Explorer (SMEX) mission launching in 2027. It consists of a large field-of-view Compton telescope that will probe with increased sensitivity the under-explored MeV gamma-ray sky (0.2-5 MeV). We will present the current status of cosipy, a Python library that will perform spectral and polarization fits, image deconvolution, and all high-level analysis tasks required by COSI's broad science goals: uncovering the origin of the Galactic positrons, mapping the sites of Galactic nucleosynthesis, improving our models of the jet and emission mechanism of gamma-ray bursts (GRBs) and active galactic nuclei (AGNs), and detecting and localizing gravitational wave and neutrino sources. The cosipy library builds on the experience gained during the COSI balloon campaigns and will bring the analysis of data in the Compton regime to a modern open-source likelihood-based code, capable of performing coherent joint fits with other instruments using the Multi-Mission Maximum Likelihood framework (3ML). In this contribution, we will also discuss our plans to receive feedback from the community by having yearly software releases accompanied by publicly-available data challenges

Pleiotropic meta-analysis of cognition, education, and schizophrenia differentiates roles of early neurodevelopmental and adult synaptic pathways

Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published genome-wide association studies (GWASs) in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results. Association analysis based on subsets (ASSET), a pleiotropic meta-analytic technique, allowed jointly associated loci to be identified and characterized. Specifically, we identified subsets of variants associated in the expected (“concordant”) direction across all three phenotypes (i.e., greater risk for schizophrenia, lower cognitive ability, and lower educational attainment); these were contrasted with variants that demonstrated the counterintuitive (“discordant”) relationship between education and schizophrenia (i.e., greater risk for schizophrenia and higher educational attainment). ASSET analysis revealed 235 independent loci associated with cognitive ability, education, and/or schizophrenia at p < 5 × 10−8. Pleiotropic analysis successfully identified more than 100 loci that were not significant in the input GWASs. Many of these have been validated by larger, more recent single-phenotype GWASs. Leveraging the joint genetic correlations of cognitive ability, education, and schizophrenia, we were able to dissociate two distinct biological mechanisms—early neurodevelopmental pathways that characterize concordant allelic variation and adulthood synaptic pruning pathways—that were linked to the paradoxical positive genetic association between education and schizophrenia. Furthermore, genetic correlation analyses revealed that these mechanisms contribute not only to the etiopathogenesis of schizophrenia but also to the broader biological dimensions implicated in both general health outcomes and psychiatric illness