A clinically validated human saliva metatranscriptomic test for global systems biology studies.

The authors report here the development of a high-throughput, automated, inexpensive and clinically validated saliva metatranscriptome test that requires less than 100 μl of saliva. RNA is preserved at the time of sample collection, allowing for ambient-temperature transportation and storage for up to 28 days. Critically, the RNA preservative is also able to inactivate pathogenic microorganisms, rendering the samples noninfectious and allowing for safe and easy shipping.

The salivary metatranscriptome as an accurate diagnostic indicator of oral cancer.

Despite advances in cancer treatment, the 5-year mortality rate for oral cancers (OC) is 40%, mainly due to the lack of early diagnostics. To advance early diagnostics for high-risk and average-risk populations, we developed and evaluated machine-learning (ML) classifiers using metatranscriptomic data from saliva samples (n = 433) collected from oral premalignant disorders (OPMD), OC patients (n = 71) and normal controls (n = 171). Our diagnostic classifiers yielded a receiver operating characteristics (ROC) area under the curve (AUC) up to 0.

Gut Microbiome Activity Contributes to Prediction of Individual Variation in Glycemic Response in Adults.

Limiting postprandial glycemic response (PPGR) is an important intervention in reducing the risk of chronic metabolic diseases and has been shown to impart significant health benefits in people with elevated levels of blood sugar. In this study, we collected gut microbiome activity data by assessing the metatranscriptome, and we measured the glycemic responses of 550 adults who consumed more than 30,000 meals, collectively, from omnivore or vegetarian/gluten-free diets. We demonstrate that gut microbiome activity, anthropometric factors, and food macronutrients modulate individual variation in glycemic response.

Discoidin-domain receptor coordinates cell-matrix adhesion and collective polarity in migratory cardiopharyngeal progenitors.

Integrated analyses of regulated effector genes, cellular processes, and extrinsic signals are required to understand how transcriptional networks coordinate fate specification and cell behavior during embryogenesis. Ciona cardiopharyngeal progenitors, the trunk ventral cells (TVCs), polarize as leader and trailer cells that migrate between the ventral epidermis and trunk endoderm. We show that the TVC-specific collagen-binding Discoidin-domain receptor (Ddr) cooperates with Integrin-β1 to promote cell-matrix adhesion.

FGF and TGFβ signaling link form and function during jaw development and evolution.

How does form arise during development and change during evolution? How does form relate to function, and what enables embryonic structures to presage their later use in adults? To address these questions, we leverage the distinct functional morphology of the jaw in duck, chick, and quail. In connection with their specialized mode of feeding, duck develop a secondary cartilage at the tendon insertion of their jaw adductor muscle on the mandible. An equivalent cartilage is absent in chick and quail.

Surrounding tissues canalize motile cardiopharyngeal progenitors towards collective polarity and directed migration.

Collectively migrating cells maintain group polarity and interpret external cues to reach their destination. The cardiogenic progenitors (also known as trunk ventral cells, TVCs) of the ascidian Ciona intestinalis provide a simple chordate model with which to study collective migration. Bilateral pairs of associated TVCs undergo a stereotyped polarized migration away from the tail towards the ventral trunk, arguably constituting the simplest possible example of directed collective migration.

Interleukin-1beta induces increased transcriptional activation of the transforming growth factor-beta-activating integrin subunit beta8 through altering chromatin architecture.

The integrin αvβ8 is a cell surface receptor for the latent domain (LAP) of the multifunctional cytokine TGF-β. Through its association with LAP, TGF-β is maintained in a latent form that must be activated to function. Binding to the integrin αvβ8 with subsequent metalloproteolytic cleavage of LAP represents a major mechanism of TGF-β activation in vivo.

Lineage analysis of micromere 4d, a super-phylotypic cell for Lophotrochozoa, in the leech Helobdella and the sludgeworm Tubifex.

The super-phylum Lophotrochozoa contains the plurality of extant animal phyla and exhibits a corresponding diversity of adult body plans. Moreover, in contrast to Ecdysozoa and Deuterostomia, most lophotrochozoans exhibit a conserved pattern of stereotyped early divisions called spiral cleavage. In particular, bilateral mesoderm in most lophotrochozoan species arises from the progeny of micromere 4d, which is assumed to be homologous with a similar cell in the embryo of the ancestral lophotrochozoan, more than 650 million years ago.

High resolution cell lineage tracing reveals developmental variability in leech.

Knowing the normal patterns of embryonic cell proliferation, migration, and differentiation is a cornerstone for understanding development. Yet for most species, the precision with which embryonic cell lineages can be determined is limited by technical considerations (the large numbers of cells, extended developmental times, opacity of the embryos), and these are exacerbated by the inherent variability of the lineages themselves. Here, we present an improved method of cell lineage tracing in the leech Helobdella, driving the expression of a nuclearly localized histone H2B:GFP (green fluorescent protein) fusion protein in selected lineages by microinjection of a plasmid vector.

Integrin alpha(v)beta8-mediated activation of transforming growth factor-beta by perivascular astrocytes: an angiogenic control switch.

Brain hemorrhage is a severe complication of both neoplastic and nonneoplastic brain disease. Mice deficient in the alpha(v)beta8 integrin display defective brain vessel formation resulting in hemorrhage and perinatal death, but the mechanism of brain hemorrhage is unknown. Because the alpha(v)beta8 integrin is expressed by astrocytes and not expressed by endothelium, paracrine interactions between astrocytes and endothelial cells could contribute to the maintenance of brain vessel integrity.

A 50-A separation of the integrin alpha v beta 3 extracellular domain C termini reveals an intermediate activation state.

The integrin alpha(v)beta(3) has been shown to exist in low and high affinity conformations. Activation to the high affinity state is thought to depend on the "switchblade-like" opening, from a low affinity bent conformation with a closed headpiece to an extended form of the integrin with an open headpiece. Activation has been shown to depend on separation of the cytoplasmic domains.