Search bioRxiv⌕ Search

Biology subjects

Aziz, F.

Publications and source records attributed to Aziz, F..

3 recordsLinked to original sources

Smad4 is essential for epiblast scaling and morphogenesis after implantation, but nonessential prior to implantation in the mouse

Bone Morphogenic Protein (BMP) signaling plays an essential and highly conserved role in axial patterning in embryos of many externally developing animal species. However, in mammalian embryos, which develop inside the mother, early development includes an additional stage known as preimplantation. During preimplantation, the epiblast lineage is segregated from the extraembryonic lineages that enable implantation and development in utero. Yet, the requirement for BMP signaling in mouse preimplantation is imprecisely defined. We show that, in contrast to prior reports, BMP signaling (as reported by SMAD1/5/9 phosphorylation) is not detectable until implantation, when it is detected in the primitive endoderm - an extraembryonic lineage. Moreover, preimplantation development appears normal following deletion of maternal and zygotic Smad4, an essential effector of BMP signaling. In fact, mice lacking maternal Smad4 are viable. Finally, we uncover a new requirement for zygotic Smad4 in epiblast scaling and cavitation immediately after implantation, via a mechanism involving FGFR/ERK attenuation. Altogether, our results demonstrate no role for BMP4/SMAD4 in the first lineage decisions during mouse development. Rather, multi-pathway signaling among embryonic and extraembryonic cell types drives epiblast morphogenesis post-implantation. Summary StatementGene expression, gene deletion, and pathway visualization evidence show that Smad4-dependent signaling is first active after mouse embryo implantation, when it promotes epiblast morphogenesis non-cell autonomously.

developmental biology↗

BCG activation of trained immunity is associated with induction of cross reactive COVID-19 antibodies in a BCG vaccinated population.

BackgroundDuring the current COVID-19 pandemic, the rate of morbidity and mortality was considerably lower in BCG vaccinated countries like Pakistan. BCG has been shown to provide cross protection to both disseminated TB as well as non related viral infections in BCG vaccinated children which is consistent with COVID-19 morbidity in the younger age group. Recently, this cross protection was attributed to trained immunity (TI) associated with BCG recall responses in the innate arm of the immune system. Little is known about the longevity of BCG Trained Immunity (TI) beyond early childhood. ObjectiveTo assess the BCG-induced recall responses in healthy individuals by cytokines secreted from the TI network and its potential role in providing cross-protection against COVID-19 and other viral infections. Study DesignIn this cross-sectional study, healthy young adults and adolescents (n=20) were recruited from 16-40 years of age, with no prior history of TB treatment, autoimmune, or chronic inflammatory condition. MethodsBCG-induced cytokine responses were assessed using prototypic markers for cells of the TI network {macrophages [M1 (TNF, IFN{gamma}), M2 (IL10)], NK (IL2), Gamma delta ({gamma}{delta}) T (IL17, IL4)} and SARS CoV2 IgG antibodies against RBD using short-term (12 hrs.) cultures assay. ResultsSignificant differences were observed in the magnitude of recall responses to BCG with macrophage cytokines showing the highest mean levels of TNF (9148 pg/ml) followed by IL10 (488 pg/ml) and IFN{gamma} (355 pg/ml). The ratio of unstimulated vs.BCG-stimulated cytokines was 132 fold higher for TNF, 40 fold for IL10, and 27 fold for IFN{gamma}. Furthermore, SARS-CoV-2 antibodies were also detected in unstimulated plasma which showed cross reactivity with BCG. ConclusionThe presence of cross reactive antibodies to SARS-CoV-2 and the relative ratio of pro-and anti-inflammatory cytokines secreted by activated TI cellular network may play a pivotal role in protection in the early stages of infection as observed during the COVID-19 pandemic in the younger age groups resulting in lower morbidity and mortality.

immunology↗

Geology and discovery record of the Trinil Pithecanthropus erectus site, Java

The scientific utility of Eugene Dubois Pithecanthropus erectus (P.e.) Skullcap (Trinil 1), Femur I (Trinil 3) and associated paleontological specimens has been impaired for over a century by questions about their provenience. Firsthand accounts and contemporaneous field photographs, presented here, extensively document the site geology and discovery history. The P.e. specimens and numerous-other fossils were unearthed in 1891-1893 from small excavations dug into a flat-lying bonebed exposed near the seasonal low-water level of the Solo River along its incised left embankment. Dubois on-site supervisors specified that the two P.e. fossils came from a [~]0.2-m-thick bonebed subunit traced at a single elevation for [~]12m from the 1891 Skullcap pit ([~]30m2) to the 1892 Femur-discovery excavation and across an enlarged 1892-1893 trench ([~]170m2). The depositional co-occurrence of the finds is supported by key documentation: the supervisors letters to Dubois about Femur I; his initial reporting to the Indies government; 1892-1893 accounts about expanding excavation of the Femur I stratum; Dubois 1891-1893 government submissions and 1894-1896 publications; confirmation by the Selenka Expedition in 1907-1908; Dubois annotations on unpublished site photographs; and a letter he wrote the year he died. Field studies in the 1930s to 1970s confirmed the essential aspects of the site geology. The bonebed of 1891-1893 contained fossils referable to the extinct Trinil fauna species Axis lydekkeri, Duboisia santeng and Stegodon trigonocephalus. The Selenka Expedition excavations had a similar assemblage in the same stratigraphic position which they named the Hauptknochenschicht. The bonebed was thin bioclast-rich gravelly volcaniclastic sandstone with taphonomic and sedimentary features indicating an unusual origin. Bioclasts range from proboscidean craniums and logs to rat teeth, freshwater mollusc shells and leaves. The terrestrial-vertebrate skeletal elements are overwhelmingly disarticulated and frequently broken. Their surfaces are little-abraded by fluvial transport. The bone fossilization is quite uniform. More than one-hundred ungulate individuals perished. No evidence has been found of hominin- or terrestrial-carnivore involvement. The bioclasts varied in density from place-to-place and vertically, and were matrix supported in the bonebed. No substantial internal depositional hiatus was reported. In combination with Trinils paleogeographic context, these features implicate a catastrophic mortality of ungulates in a population aggregation along the floodplain of a perennial paleo-river, followed by lahar-flood transport and deposition of gravel-size lithic- and biotic-materials. Trinil provides evidence favoring a broad archaic-hominin presence in southern Sundaland. The Trinil fauna is a lynch-pin in a long-lasting paleobiogeographic association between H. erectus and certain lineages of large bovids, cervids, proboscideans, rhinoceros, suids and tiger. The bonebeds paleogeographic setting exemplifies the stratovolcanic drainages that H. erectus occupied for >0.8 million years in Java, including the watershed of a marine delta [~]150km east of Trinil, a volcanic island [~]100km north of Trinil, and areas to its west for 500km (where species associated with Trinil H. erectus occur). In the Java Sea (Sunda Shelf), seismic data image immense Pleistocene river- and coastal-terranes which archaic hominins and other large-mammals, like those at Trinil, might have inhabited.

paleontology↗