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Labor is a complex physiological process requiring a well-orchestrated dialogue between the mother and fetus. However, the cellular contributions and communications that facilitate maternal-fetal cross-talk in labor have not been fully elucidated. Here, single-cell RNA sequencing (scRNA-seq) was applied to decipher maternal-fetal signaling in the human placenta during term labor. First, a single-cell atlas of the human placenta was established, demonstrating that maternal and fetal cell types underwent changes in transcriptomic activity during labor. Cell types most affected by labor were fetal stromal and maternal decidual cells in the chorioamniotic membranes (CAMs) and maternal and fetal myeloid cells in the placenta. Cell-cell interaction analyses showed that CAM and placental cell types participated in labor-driven maternal and fetal signaling, including the collagen, C-X-C motif ligand (CXCL), tumor necrosis factor (TNF), galectin, and interleukin-6 (IL-6) pathways. Integration of scRNA-seq data with publicly available bulk transcriptomic data showed that placenta-derived scRNA-seq signatures could be monitored in the maternal circulation throughout gestation and in labor. Moreover, comparative analysis revealed that placenta-derived signatures in term labor were mirrored by those in spontaneous preterm labor and birth. Furthermore, we demonstrated that early in gestation, labor-specific, placenta-derived signatures could be detected in the circulation of women destined to undergo spontaneous preterm birth, with either intact or prelabor ruptured membranes. Collectively, our findings provide insight into the maternal-fetal cross-talk of human parturition and suggest that placenta-derived single-cell signatures can aid in the development of noninvasive biomarkers for the prediction of preterm birth. Editor's summary: Spontaneous labor involves complex communication between maternal and fetal cells, but our understanding of this cross-talk is limited. Here, Garcia-Flores and colleagues generated a single-cell atlas of the human placenta during term labor and performed cell-cell interaction analyses to better understand labor-driven maternal and fetal cell signaling changes. By combining their single-cell RNA-sequencing (RNA-seq) data with bulk RNA-seq datasets, they showed that placental signatures could be monitored in maternal blood during pregnancy and labor and that the signals in term labor were also present in cases of spontaneous preterm labor. Furthermore, signals were present in the blood of pregnant women who went on to experience spontaneous preterm birth, suggesting that it might be possible to develop tests to predict development of spontaneous preterm birth. —Melissa L. Norton [ABSTRACT FROM AUTHOR]

Context. Monitoring the population dynamics of threatened species requires a landscape-scale understanding of their distribution over time. However, detectability is inherently low for rare, widely dispersed, and cryptic species. For animals that vocalise, passive acoustic recorders allow for efficient and repeated surveys over a large geographic area, increasing inference in relation to detectability and occupancy. Aims. Our aim was to determine how well acoustic surveys, combined with automated species detection, identified the presence of the critically endangered plains-wanderer (Pedionomus torquatus) relative to a traditional method of nocturnal spotlighting surveys at sites across the Northern Plains of Victoria, Australia. Methods. Using Hidden Markov Models, we created 17 different plains-wanderer call recognisers by varying input parameters and assessed their performance on the same training and testing audio dataset. We then applied our best-performing recogniser to a field audio dataset to estimate detectability and compared the presence of plains-wanderers at sites paired with nocturnal surveys. Key results. Recognisers varied in their overall performance in detecting individual plains-wanderer calls but were equally effective at determining whether any plains-wanderer calls were detected at a site within ourtraining and testing datasets. Although survey effort was not standardised across field survey methods, we found audio surveys and nocturnal spotlight surveys were equally successful at establishing site-level occupancy; however, acoustic surveys provide the potential to survey more sites over a given time period. Conclusions. We suggest acoustic surveys can be an effective and efficient means to document occupancy at the landscape scale, facilitating prioritisation of nocturnal surveys to assess population demographic parametersincluding abundance and breeding status. Implications.Acoustic surveys can provide a complementary method to establish occupancy for cryptic, vocally active, threatened species. We provide recommendations on ways to develop an effective acoustic monitoring program workflow, from data collection to acoustic analysis, that can be used by different user groups. [ABSTRACT FROM AUTHOR]

The Urysohn space is a separable complete metric space with two fundamental properties: (a) universality: every separable metric space can be isometrically embedded in it; (b) ultrahomogeneity: every finite isometry between two finite subspaces can be extended to an auto-isometry of the whole space. The Urysohn space is uniquely determined up to isometry within separable metric spaces by these two properties. We introduce an analogue of the Urysohn space for diversities, a recently developed variant of the concept of a metric space. In a diversity any finite set of points is assigned a non-negative value, extending the notion of a metric which only applies to unordered pairs of points.We construct the unique separable complete diversity that it is ultrahomogeneous and universal with respect to separable diversities.

Dysregulation of the PI3K/AKT pathway is a common occurrence in high‐grade serous ovarian carcinoma (HGSOC), with the loss of the tumour suppressor PTEN in HGSOC being associated with poor prognosis. The cellular mechanisms of how PTEN loss contributes to HGSOC are largely unknown. We here utilise time‐lapse imaging of HGSOC spheroids coupled to a machine learning approach to classify the phenotype of PTEN loss. PTEN deficiency induces PI(3,4,5)P3‐rich and ‐dependent membrane protrusions into the extracellular matrix (ECM), resulting in a collective invasion phenotype. We identify the small GTPase ARF6 as a crucial vulnerability of HGSOC cells upon PTEN loss. Through a functional proteomic CRISPR screen of ARF6 interactors, we identify the ARF GTPase‐activating protein (GAP) AGAP1 and the ECM receptor β1‐integrin (ITGB1) as key ARF6 interactors in HGSOC regulating PTEN loss‐associated invasion. ARF6 functions to promote invasion by controlling the recycling of internalised, active β1‐integrin to maintain invasive activity into the ECM. The expression of the CYTH2‐ARF6‐AGAP1 complex in HGSOC patients is inversely associated with outcome, allowing the identification of patient groups with improved versus poor outcome. ARF6 may represent a therapeutic vulnerability in PTEN‐depleted HGSOC. Synopsis: Loss of the tumor suppressor PTEN is associated with poor prognosis in high‐grade serous ovarian carcinoma (HGSOC) but its cellular role remains unclear. Here, PTEN deficiency is shown to drive PI(3,4,5)P3‐dependent cancer cell invasion via enhancing recycling of pro‐invasive endocytic cargos. PTEN depletion in three‐dimensional HGSOC spheroids induces PI(3,4,5)P3‐rich membrane protrusions in an ARF6‐dependent manner.A CYTH2‐ARF6‐AGAP1 module regulates PTEN loss‐associated invasion, with GEF CYTH2 being PI(3,4,5)P3‐responsive.The CYTH2‐ARF6‐AGAP1 module localises to PI(3,4,5)P3‐rich protrusion tips, supporting recycling of β1‐integrin and extracellular matrix invasion.Expression of the ARF6 complex in HGSOC patients is inversely correlated with outcome. [ABSTRACT FROM AUTHOR]

Diversities are like metric spaces, except that every finite subset, instead of just every pair of points, is assigned a value. Just as there is a theory of minimal distortion embeddings of fiite metric spaces into L1, there is a similar, yet undeveloped, theory for embedding finite diversities into the diversity analogue of L1 spaces. In the metric case, it iswell known that an n-point metric space can be embedded into L1 withO(log n) distortion. For diversities, the optimal distortion is unknown. Here, we establish the surprising result that symmetric diversities, those in which the diversity (value) assigned to a set depends only on its cardinality, can be embedded in L1 with constant distortion.