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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 generalized circumradius of a set of points A ⊆ R d with respect to a convex body K equals the minimum value of λ ≥ 0 such that a translate of λ K contains A. Each choice of K gives a different function on the set of bounded subsets of R d ; we characterize which functions can arise in this way. Our characterization draws on the theory of diversities, a recently introduced generalization of metrics from functions on pairs to functions on finite subsets. We additionally investigate functions which arise by restricting the generalized circumradius to a finite subset of R d . We obtain elegant characterizations in the case that K is a simplex or parallelotope. [ABSTRACT FROM AUTHOR]

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]

The essay titled "We are the system" explores the role of personal experiences and diversity in academic discourse, specifically in the field of cell biology. The author argues that acknowledging personal perspectives is important because the academic system is made up of fallible and biased individuals. The essay focuses on the challenges faced by the LGBT+ community in STEM fields and emphasizes the need for open dialogue and understanding. The author suggests that academic conferences and initiatives should address diversity and encourages listening to colleagues with different characteristics to gain a better understanding of their experiences. The article emphasizes the importance of having difficult conversations about equity, diversity, and inclusion in academic spaces, and highlights the need for respectful and inclusive dialogue. The author also emphasizes the importance of compassion and understanding for perspectives that may differ from one's own, and encourages the academic community to create space for diverse voices and experiences. [Extracted from the article]

The standard models of sequence evolution on a tree determine probabilities for every character or site pattern. A flattening is an arrangement of these probabilities into a matrix, with rows corresponding to all possible site patterns for one set A of taxa and columns corresponding to all site patterns for another set B of taxa. Flattenings have been used to prove difficult results relating to phylogenetic invariants and consistency and also form the basis of several methods of phylogenetic inference. We prove that the rank of the flattening equals r ν T (A | B) , where r is the number of states and ν T (A | B) is the minimum size of a vertex cut separating A from B. When T is binary the rank of the flattening equals r ℓ T (A | B) where ℓ T (A | B) equals the parsimony length of the binary character separating A and B. We provide a direct proof that requires little more than undergraduate algebra, but note that the formula could also be derived from work by Casanellas and Fernández-Sánchez (2011) on phylogenetic invariants. [ABSTRACT FROM AUTHOR]

Purpose: Epithelioid glioblastoma is an unusual histologic variant of malignant glioma. The present study investigates both the genomic and transcriptomic determinants that may promote the development of this tumor. Methods: Whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) were performed on an epithelioid glioblastoma, along with a specific bioinformatic pipeline to generate electronic karyotyping and investigate the tumor immune microenvironment. Microdissected sections containing typical glioblastoma features and epithelioid morphology were analyzed separately using the same methodologies. Results: An epithelioid glioblastoma, with immunopositivity for GFAP, Olig-2, and ATRX but negative for IDH-1 and p53, was identified. The tumor cell content from microdissection was estimated to be 85-90% for both histologic tumor components. WES revealed that both glioma and epithelioid sections contained identical point mutations in PTEN, RB1, TERT promoter, and TP53. Electronic karyotype analysis also revealed similar chromosomal copy number alterations, but the epithelioid component showed additional abnormalities that were not found in the glioblastoma component. The tumor immune microenvironments were strikingly different and WTS revealed high levels of transcripts frommyeloid cells as well asM1 andM2macrophages in the glioma section, while transcripts from CD4+ lymphocytes and NK cells predominated in the epithelioid section. Conclusion: Epithelioid glioblastoma may be genomically more unstable and oncogenically more advanced, harboring an increased number of mutations and karyotype abnormalities, compared to typical glioblastomas. The tumor immune microenvironment is also different. [ABSTRACT FROM AUTHOR]

Context: Many threatened species persist in modified landscapes. Species in these landscapes often inhabit vegetation strips adjacent to linear structures such as roads, railways and artificial waterways. These vegetation strips may act as refugia or provide resources, but the associated structures (e.g. roads) may also act as barriers to movement. The southern brown bandicoot (eastern subspecies) is listed as Endangered in Australia and is known to inhabit modified landscapes. Aim: We aim to determine the extent of occupancy of southern brown bandicoots and the relative importance of different habitat types. Our data are intended to provide a baseline for future monitoring of changes to bandicoot populations, and to further our understanding of the relative importance of different habitat types for management and conservation. Methods: We conducted a remote-camera survey of southern brown bandicoots, at 98 locations across a 60 000 ha region south-east of Melbourne. Bandicoots in this area inhabit patches of remnant habitat in reserves and remnant, modified or non-native vegetation strips along roadsides and artificial waterways created in the 19th century to drain swampland. These habitat fragments sit within a matrix of agricultural, residential and commercial land. Key results: Our results suggest that bandicoot occupancy is higher along artificial waterways (0.76) than along roadsides (0.35) or within reserves (0.39). Implications: Habitat along waterways is often different from remnants, with a mix of weedy and native vegetation. The implication of this is a potential conflict between habitat and vegetation management for bandicoots, weed control and maintenance of drains and associated levees. Like many threatened species, the Endangered southern brown bandicoot persists in modified landscapes. In our study area, located to the south-east of Melbourne, we found that bandicoot occupancy is higher along artificial waterways (drains) than along roadsides or within reserves. There is a potential conflict between habitat and vegetation management for bandicoots, weed control and maintenance of drains and associated levees. Photograph by remote camera. [ABSTRACT FROM AUTHOR]

Grey's Skink Menetia greyii is reported from 2 locations in grassland vegetation at Mount Cottrell on the Keilor Plains of southern Victoria. These records represent the most southern detections of this species, and the first reported south of the Great Dividing Range. One lizard was collected in a pitfall trap, the other under a roof tile, both within Natural Temperate Grassland dominated by Kneed-spear Grass Austrostipa bigeniculata and Kangaroo Grass Themeda triandra. [ABSTRACT FROM AUTHOR]

Single cell profiling by genetic, proteomic and imaging methods has expanded the ability to identify programmes regulating distinct cell states. The 3-dimensional (3D) culture of cells or tissue fragments provides a system to study how such states contribute to multicellular morphogenesis. Whether cells plated into 3D cultures give rise to a singular phenotype or whether multiple biologically distinct phenotypes arise in parallel is largely unknown due to a lack of tools to detect such heterogeneity. Here we develop Traject3d (Trajectory identification in 3D), a method for identifying heterogeneous states in 3D culture and how these give rise to distinct phenotypes over time, from label-free multi-day time-lapse imaging. We use this to characterise the temporal landscape of morphological states of cancer cell lines, varying in metastatic potential and drug resistance, and use this information to identify drug combinations that inhibit such heterogeneity. Traject3d is therefore an important companion to other single-cell technologies by facilitating real-time identification via live imaging of how distinct states can lead to alternate phenotypes that occur in parallel in 3D culture. There are currently a lack of tools to detect heterogeneity in 3D cultures. Here the authors report Traject3d as a framework to identify heterogeneous states in 3D culture and to understand how these give rise to distinct phenotypes using label-free multi-day time-lapse imaging. [ABSTRACT FROM AUTHOR]

Patient‐derived organoids and cellular spheroids recapitulate tissue physiology with remarkable fidelity. We investigated how engagement with a reconstituted basement membrane in three dimensions (3D) supports the polarized, stress resilient tissue phenotype of mammary epithelial spheroids. Cells interacting with reconstituted basement membrane in 3D had reduced levels of total and actin‐associated filamin and decreased cortical actin tension that increased plasma membrane protrusions to promote negative plasma membrane curvature and plasma membrane protein associations linked to protein secretion. By contrast, cells engaging a reconstituted basement membrane in 2D had high cortical actin tension that forced filamin unfolding and endoplasmic reticulum (ER) associations. Enhanced filamin‐ER interactions increased levels of PKR‐like ER kinase effectors and ER‐plasma membrane contact sites that compromised calcium homeostasis and diminished cell viability. Consequently, cells with decreased cortical actin tension had reduced ER stress and survived better. Consistently, cortical actin tension in cellular spheroids regulated polarized basement membrane membrane deposition and sensitivity to exogenous stress. The findings implicate cortical actin tension‐mediated filamin unfolding in ER function and underscore the importance of tissue mechanics in organoid homeostasis. Synopsis: How three‐dimensional spheroid cultures of mammary epithelial cells retain superior long‐term viability and stress resilience remains unclear. This work uncovers coupling between extracellular matrix (ECM) topology, cortical actin tension and endoplasmic reticulum (ER) function, which serves to safeguard protein secretion and cellular stress response. High cortical actin tension in 2D mammary epithelial cell cultures facilitates filamin‐PERK interaction and compromises ER function.In 3D spheroid cultures, mammary epithelial cell ‐ ECM interactions reduce cortical actin tension and filamin binding to PERK, maintaining ER homeostasis.Reduced cortical actin tension increases plasma membrane protrusion size and duration, favoring recruitment of negative curvature‐binding proteins that facilitate protein secretion. [ABSTRACT FROM AUTHOR]

The Journal of Cell Science has published a special issue on cell and tissue polarity. Cell polarization refers to the asymmetric distribution of cellular components, allowing for specialization and different cellular processes within individual cells. This concept is fundamental to various biological functions, such as feeding, propulsion, and the formation of tissues. The issue includes original research articles, reviews, and commentaries that explore the mechanisms and implications of cell and tissue polarity. The issue also highlights the work of early-career researchers and provides insights into the peer review process. [Extracted from the article]

Working memory (WM) is the system responsible for maintaining and manipulating information, in the face of ongoing distraction. In turn, WM span is perceived to be an individual-differences construct reflecting the limited capacity of this system. Recently, however, there has been some evidence to suggest that WM capacity can increase through training, raising the possibility that training can functionally alter the neural structures supporting WM. To address the hypothesis that the neural substrates underlying WM are targeted by training, we conducted a meta-analysis of functional magnetic resonance imaging (fMRI) studies of WM training using Activation Likelihood Estimation (ALE). Our results demonstrate that WM training is associated exclusively with decreases in blood oxygenation level-dependent (BOLD) responses in clusters within the fronto-parietal system that underlie WM, including the bilateral inferior parietal lobule (BA 39/40), middle (BA 9) and superior (BA 6) frontal gyri, and medial frontal gyrus bordering on the cingulate gyrus (BA 8/32). We discuss the various psychological and physiological mechanisms that could be responsible for the observed reductions in the BOLD signal in relation to WM training, and consider their implications for the construct of WM span as a limited resource. [ABSTRACT FROM AUTHOR]

February is LGBT+ history month, and to celebrate, Journal of Cell Science Editorial Advisory Board member David Bryant organised a conversation with a selection of scientists to explore their experiences of being LGBT+ in academia. [ABSTRACT FROM AUTHOR]

In many phylogenetic applications, such as cancer and virus evolution, time trees, evolutionary histories where speciation events are timed, are inferred. Of particular interest are clock-like trees, where all leaves are sampled at the same time and have equal distance to the root. One popular approach to model clock-like trees is coalescent theory, which is used in various tree inference software packages. Methodologically, phylogenetic inference methods require a tree space over which the inference is performed, and the geometry of this space plays an important role in statistical and computational aspects of tree inference algorithms. It has recently been shown that coalescent tree spaces possess a unique geometry, different from that of classical phylogenetic tree spaces. Here we introduce and study a space of discrete coalescent trees. They assume that time is discrete, which is natural in many computational applications. This tree space is a generalisation of the previously studied ranked nearest neighbour interchange space, and is built upon tree-rearrangement operations. We generalise existing results about ranked trees, including an algorithm for computing distances in polynomial time, and in particular provide new results for both the space of discrete coalescent trees and the space of ranked trees. We establish several geometrical properties of these spaces and show how these properties impact various algorithms used in phylogenetic analyses. Our tree space is a discretisation of a previously introduced time tree space, called t-space, and hence our results can be used to approximate solutions to various open problems in t-space. [ABSTRACT FROM AUTHOR]

Microbial studies typically involve the sequencing and assembly of draft genomes for individual microbes or whole microbiomes. Given a draft genome, one first task is to determine its phylogenetic context, that is, to place it relative to the set of related reference genomes. We provide a new interactive graphical tool that addresses this task using Mash sketches to compare against all bacterial and archaeal representative genomes in the Genome Taxonomy Database taxonomy, all within the framework of SplitsTree5. The phylogenetic context of the query sequences is then displayed as a phylogenetic outline, a new type of phylogenetic network that is more general than a phylogenetic tree, but significantly less complex than other types of phylogenetic networks. We propose to use such networks, rather than trees, to represent phylogenetic context, because they can express uncertainty in the placement of taxa, whereas a tree must always commit to a specific branching pattern. We illustrate the new method using a number of draft genomes of different assembly quality. [ABSTRACT FROM AUTHOR]

The signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive cellular responses occur is unclear. Here, we report development of 3-Dimensional culture analyses to separately quantify growth and invasion. We identify that alternate variants of IQSEC1, an ARF GTPase Exchange Factor, act as switches to promote invasion over growth by controlling phosphoinositide metabolism. All IQSEC1 variants activate ARF5- and ARF6-dependent PIP5-kinase to promote PI(3,4,5)P3-AKT signalling and growth. In contrast, select pro-invasive IQSEC1 variants promote PI(3,4,5)P3 production to form invasion-driving protrusions. Inhibition of IQSEC1 attenuates invasion in vitro and metastasis in vivo. Induction of pro-invasive IQSEC1 variants and elevated IQSEC1 expression occurs in a number of tumour types and is associated with higher-grade metastatic cancer, activation of PI(3,4,5)P3 signalling, and predicts long-term poor outcome across multiple cancers. IQSEC1-regulated phosphoinositide metabolism therefore is a switch to induce invasion over growth in response to the same external signal. Targeting IQSEC1 as the central regulator of this switch may represent a therapeutic vulnerability to stop metastasis. The signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive responses occur is unclear. Here, the authors show that alternate isoforms of the ARF GTPase exchange factor IQSEC1 direct phosphoinositide metabolism to control this switch. [ABSTRACT FROM AUTHOR]

Clinical chorioamnionitis at term is considered the most common infection-related diagnosis in labor and delivery units worldwide. The syndrome affects 5–12% of all term pregnancies and is a leading cause of maternal morbidity and mortality as well as neonatal death and sepsis. The objectives of this study were to determine the (1) amniotic fluid microbiology using cultivation and molecular microbiologic techniques; (2) diagnostic accuracy of the clinical criteria used to identify patients with intra-amniotic infection; (3) relationship between acute inflammatory lesions of the placenta (maternal and fetal inflammatory responses) and amniotic fluid microbiology and inflammatory markers; and (4) frequency of neonatal bacteremia. This retrospective cross-sectional study included 43 women with the diagnosis of clinical chorioamnionitis at term. The presence of microorganisms in the amniotic cavity was determined through the analysis of amniotic fluid samples by cultivation for aerobes, anaerobes, and genital mycoplasmas. A broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry was also used to detect bacteria, select viruses, and fungi. Intra-amniotic inflammation was defined as an elevated amniotic fluid interleukin-6 (IL-6) concentration ≥2.6 ng/mL. (1) Intra-amniotic infection (defined as the combination of microorganisms detected in amniotic fluid and an elevated IL-6 concentration) was present in 63% (27/43) of cases; (2) the most common microorganisms found in the amniotic fluid samples were Ureaplasma species, followed by Gardnerella vaginalis; (3) sterile intra-amniotic inflammation (elevated IL-6 in amniotic fluid but without detectable microorganisms) was present in 5% (2/43) of cases; (4) 26% of patients with the diagnosis of clinical chorioamnionitis had no evidence of intra-amniotic infection or intra-amniotic inflammation; (5) intra-amniotic infection was more common when the membranes were ruptured than when they were intact (78% [21/27] vs. 38% [6/16]; p=0.01); (6) the traditional criteria for the diagnosis of clinical chorioamnionitis had poor diagnostic performance in identifying proven intra-amniotic infection (overall accuracy, 40–58%); (7) neonatal bacteremia was diagnosed in 4.9% (2/41) of cases; and (8) a fetal inflammatory response defined as the presence of severe acute funisitis was observed in 33% (9/27) of cases. Clinical chorioamnionitis at term, a syndrome that can result from intra-amniotic infection, was diagnosed in approximately 63% of cases and sterile intra-amniotic inflammation in 5% of cases. However, a substantial number of patients had no evidence of intra-amniotic infection or intra-amniotic inflammation. Evidence of the fetal inflammatory response syndrome was frequently present, but microorganisms were detected in only 4.9% of cases based on cultures of aerobic and anaerobic bacteria in neonatal blood. [ABSTRACT FROM AUTHOR]

Diversities are a generalization of metric spaces in which a non-negative value is assigned to all finite subsets of a set, rather than just to pairs of points. Here we provide an analogue of the theory of negative-type metrics for diversities. We introduce negative-type diversities, and show that, as in the metric space case, they are a generalization of L 1 -embeddable diversities. We provide a number of characterizations of negative-type diversities, including a geometric characterization. Much of the recent interest in negative-type metrics stems from the connections between metric embeddings and approximation algorithms. We extend some of this work into the diversity setting, showing that lower bounds for embeddings of negative-type metrics into L 1 can be extended to diversities by using recently established extremal results on hypergraphs. [ABSTRACT FROM AUTHOR]

We describe a new and computationally efficient Bayesian methodology for inferring species trees and demographics from unlinked binary markers. Likelihood calculations are carried out using diffusion models of allele frequency dynamics combined with novel numerical algorithms. The diffusion approach allows for analysis of data sets containing hundreds or thousands of individuals. The method, which we call Snapper , has been implemented as part of the BEAST2 package. We conducted simulation experiments to assess numerical error, computational requirements, and accuracy recovering known model parameters. A reanalysis of soybean SNP data demonstrates that the models implemented in Snapp and Snapper can be difficult to distinguish in practice, a characteristic which we tested with further simulations. We demonstrate the scale of analysis possible using a SNP data set sampled from 399 fresh water turtles in 41 populations. [Bayesian inference; diffusion models; multi-species coalescent; SNP data; species trees; spectral methods.] [ABSTRACT FROM AUTHOR]

Tree comparison metrics have proven to be an invaluable aide in the reconstruction and analysis of phylogenetic (evolutionary) trees. The path-length distance between trees is a particularly attractive measure as it reflects differences in tree shape as well as differences between branch lengths. The distance equals the sum, over all pairs of taxa, of the squared differences between the lengths of the unique path connecting them in each tree. We describe an O (n log n) time for computing this distance, making extensive use of tree decomposition techniques introduced by Brodal et al. (Algorithmica 38(2):377–395, 2004). [ABSTRACT FROM AUTHOR]

Background: We discuss the ethical decision points in a case report that describes a novel COL1A1 mutation associated to Osteogenesis Imperfecta type II, but with a non-lethal outcome.Case: A 33-year-old female underwent a 21-week ultrasound that revealed short bowed femurs and humeri with old fractures and bowed tibias and fibulas. Amniotic fluid testing revealed a novel COL1A1 mutation (c.1840G>A; p.Gly614Arg). OI Type II diagnosis was made. A previously reported mutation of the same gene but different locus (c.1840G>C; p.Gly614Arg) led to a lethal form of OI type II. The newborn was delivered via a cesarean delivery and intravenous bisphosphonates (Zaledronic acid) was administered every 3 months. Currently the infant is 22 months old, is growing, with mild bilateral conductive hearing loss.Conclusion: The unexpected clinical outcome should serve as a reminder that phenotypic variability can occur with genetic mutations. Our case shows that the diagnosis of the type of OI should be based not only on clinical findings and genetic investigations but also on the clinical course over time. [ABSTRACT FROM AUTHOR]

Anthropogenic influences and pressure from feral predators on the Southern Brown Bandicoot Isoodon obesulus obesulus have resulted in the contraction of its distribution, such that it now exhibits a disjunct distribution across its former range. Isolated populations have the potential to become genetic bottlenecks while at the same time being valuable as reservoirs of genetic variability. This paper investigates the occurrence of the Southern Brown Bandicoot on Chinaman Island, Western Port, a locality previously reported as having evidence of the species. In this study, the first direct evidence was obtained of the Southern Brown Bandicoot occurring on the island. Habitat on Chinaman Island was found to be complex. It is described here according to Ecological Vegetation Classes, which are mapped across the island, and physical structure, which was quantified at sampling locations in this area. [ABSTRACT FROM AUTHOR]

Hot spotting is a thermal localisation phenomenon in which multiple hot regions form on a brake disc surface during high-energy and/or high-speed braking events. As an undesired problem, hot spots can result in high-order brake judder, an audible droning noise and thermal cracking. This paper presents a finite element model for hot-spot modelling which introduces the classical axisymmetric assumptions to the brake pad in three dimensions by scaling the material properties combined with a subroutine to simulate the heat generation instead of modelling the rotation of the brake pad. The results from the initial feasibility models showed significant improvement in the computing efficiency with acceptable accuracy when compared with a traditional finite element model without such simplifications. This method was then applied to three-dimensional simulations of hot spotting on a realistic ventilated brake disc–pad pair, and the results showed good correlation with the experiments. In order to improve the understanding of the hot-spotting mechanism, parametric studies were performed including the effects of a solid-disc geometry and a ventilated-disc geometry, the rotational speed and energy, the pins, the disc run-out and the brake pad length. Based on the analysis of the results, it was identified that the vents and the pins affected the hot-spot distribution. The speed was shown to be more important in the hot-spot generation time and the hot-spot distribution than either the pressure or the total energy input was. The brake disc run-out was shown to affect the magnitude of both the hot-spot temperature and the hot-spot height because of the non-linear relationship between the local deformation, the contact pressure and the heat generation. Finally, increasing the brake pad length generated fewer hot spots, but the temperature of each hot spot increased. [ABSTRACT FROM AUTHOR]

Abstract: Bio‐based and bio‐degradable plastics such as polybutylene succinate (PBS) have the potential to become sustainable alternatives to petrochemical‐based plastics. Polybutylene succinate can be produced from bio‐based succinic acid and 1,4‐butanediol using first‐generation (1G) or second‐generation (2G) sugars. A cradle‐to‐grave environmental assessment was performed for PBS products in Europe to investigate the non‐renewable energy use (NREU) and greenhouse gas (GHG) impacts. The products investigated are single‐use trays and agricultural film, with incineration, industrial composting and degradation on agricultural land as end‐of‐life scenarios. Both end products manufactured from fully bio‐based PBS and from partly bio‐based PBS (made from bio‐based succinic acid and fossil fuel‐based 1,4 butanediol) were analysed. We examine corn (1G) as well as corn stover, wheat straw, miscanthus and hardwood as 2G feedstocks. For the cradle‐to‐grave system, 1G fully bio‐based PBS plastic products were found to have environmental impacts comparable with their petrochemical incumbents, while 2G fully bio‐based PBS plastic products allow to reduce NREU and GHG by around one third under the condition of avoidance of concentration of sugars and energy integration of the pretreatment process with monomer production. Without energy integration and with concentration of sugars (i.e., separate production), the impacts of 2G fully bio‐based PBS products are approximately 15–20% lower than those of 1G fully bio‐based PBS products. The environmental analysis of PBS products supports the value proposition related to PBS products while also pointing out areas requiring further research and development. © 2018 Society of Chemical Industry and John Wiley & Sons, Ltd [ABSTRACT FROM AUTHOR]

Abstract: Recent studies have suggested that spatial patterns of intraspecific diversity can be influenced by density‐dependent processes, which can inhibit effective migration of new lineages to established populations. How mechanisms such as dispersal and disturbance influence these processes is, however, still poorly understood. We hypothesised that (1) species with leptokurtic dispersal (frequent on small scales but rare on larger scales) would show no spatial structure on small scales and strong structure on large scales, and (2) disturbance would influence the chance of genetic turnover in a population. We tested these hypotheses using empirical genetic (mtDNA) data from field observations of a model taxon (the buoyant, forest‐forming kelp Durvillaea, which exhibits leptokurtic dispersal distribution), and by conducting simulation analyses. Our data supported the first hypothesis, with no spatial structure detected on fine (metres) scales despite evidence of strong structure on larger (tens to hundreds of kilometres) scales. The second hypothesis was also supported, with simulations showing that disturbance increased the rate at which structure developed, and reduced the time to fixation (monopolisation by a single lineage). The chance of any lineage reaching fixation was directly related to its initial proportion in the population, and this relationship was unaffected by changes in disturbance size or dispersal capacity. We conclude that, in the absence of selection, extirpation is typically a prerequisite for population‐genetic “turnover”, with remnant (refugial) individuals otherwise outnumbering immigrants. Synthesis. Disturbance plays a critical role in releasing density‐dependent blocks to colonisation, and thus enables lineage turnover within species. Our results indicate that although both disturbance size and dispersal capacity play important roles in the formation of spatial structure within species, unless a population is totally extirpated, establishment of genetic lineages from elsewhere (turnover) is unlikely even for species that can disperse well. [ABSTRACT FROM AUTHOR]

In prokaryotes, known mechanisms of lateral gene transfer (transformation, transduction, conjugation, and gene transfer agents) generate new combinations of genes among chromosomes during evolution. In eukaryotes, whose host lineage is descended from archaea, lateral gene transfer from organelles to the nucleus occurs at endosymbiotic events. Recent genome analyses studying gene distributions have uncovered evidence for sporadic, discontinuous events of gene transfer from bacteria to archaea during evolution. Other studies have used traditional models designed to investigate gene family size evolution (Count) to support claims that gene transfer to archaea was continuous during evolution, rather than involving occasional periodic mass gene influx events. Here, we show that the methodology used in analyses favoring continuous gene transfers to archaea was misapplied in other studies and does not recover known events of single simultaneous origin for many genes followed by differential loss in real data: plastid genomes. Using the same software and the same settings, we reanalyzed presence/absence pattern data for proteins encoded in plastid genomes and for eukaryotic protein families acquired from plastids. Contrary to expectations under a plastid origin model, we found that the methodology employed inferred that gene acquisitions occurred uniformly across the plant tree. Sometimes as many as nine different acquisitions by plastid DNA were inferred for the same protein family. That is, the methodology that recovered gradual and continuous lateral gene transfer among lineages for archaea obtains the same result for plastids, even though it is known that massive gains followed by gradual differential loss is the true evolutionary process that generated plastid gene distribution data. Our findings caution against the use of models designed to study gene family size evolution for investigating gene transfer processes, especially when transfers involving more than one gene per event are possible. [ABSTRACT FROM AUTHOR]

In many types of tubules, continuity of the lumen is paramount to tubular function, yet how tubules generate lumen continuity in vivo is not known. We recently found that the F-actin-binding protein afadin is required for lumen continuity in developing renal tubules, though its mechanism of action remains unknown. Here, we demonstrate that afadin is required for lumen continuity by orienting the mitotic spindle during cell division. Using an in vitro 3D cyst model, we find that afadin localizes to the cell cortex adjacent to the spindle poles and orients the mitotic spindle. In tubules, cell division may be oriented relative to two axes: longitudinal and apical-basal. Unexpectedly, in vivo examination of early-stage developing nephron tubules reveals that cell division is not oriented in the longitudinal (or planar-polarized) axis. However, cell division is oriented perpendicular to the apicalbasal axis. Absence of afadin in vivo leads to misorientation of apicalbasal cell division in nephron tubules. Together, these results support a model whereby afadin determines lumen placement by directing apical-basal spindle orientation, resulting in a continuous lumen and normal tubule morphogenesis. [ABSTRACT FROM AUTHOR]

Natural grasslands in southern Australia commonly exist in altered states. One widespread altered state is grassland pasture dominated by cool-season (C3) native grasses maintained by ongoing grazing. This study explores the consequences of removing grazing and introducing fire as a conservation management tool for such a site. We examined the abundance of two native and three exotic species, across a mosaic of fire regimes that occurred over a three-year period: unburnt, summer wild-fire (>2 years previous), autumn management fire (<1 year previously) and burnt in both fires. Given that one aim of conservation management is to increase native species at the expense of exotics, the impacts of the fires were largely positive. Native grasses were at higher cover levels in the fire-managed vegetation than in the unburnt vegetation. Of the three exotic species, one was consistently at lower density in the burnt plots compared to the unburnt plots, while the others were lower only in those plots burnt in summer. The results show that the response of a species varies significantly between different fire events, and that the effects of one fire can persist through subsequent fires. Importantly, some of the effects were large, with changes in the density of plants of over 100-fold. Fire is potentially a cost-effective tool to assist the ecological restoration of retired grassland pastures at large scales. [ABSTRACT FROM AUTHOR]

There are several types of disc brake instabilities associated with the brake systems; however, they are usually classified into two main categories depending on the frequency range: brake groan 0-300 Hz and brake squeal 1-16 kHz. The groan is associated with the stick-slip motion while the squeal is associated with the modal coupling. This paper presents a detailed analysis of low frequency noise (0-300 Hz) in a commercial vehicle trailer disc brake as a result of stick-slip vibration. A range of experimental techniques are used to understand the characteristic behaviour of the caliper and the brake pads during braking events on a laboratory test rig. The analysed brake system comprised a full disc brake assembly and the trailer suspension system with a beam axle. Laser-based optical displacement sensors were used to investigate the deformation of the caliper body and the brake pads during a braking application. The contact pressure distribution at the disc/pad interfaces were also measured to gain more insight into the contact profile of the pad surfaces. Results revealed that the stick-slip phenomenon, in this study, was a result of the combination of the deformation of the caliper and the friction material formulation of the brake pads. In addition, it was observed through the testing of two different sets of pads that a low compression modulus would help to reduce the stick-slip phenomenon. [ABSTRACT FROM AUTHOR]

Tumor progression alters the composition and physical properties of the extracellular matrix. Particularly, increased matrix stiffness has profound effects on tumor growth and metastasis. While endothelial cells are key players in cancer progression, the influence of tumor stiffness on the endothelium and the impact on metastasis is unknown. Through quantitative mass spectrometry, we find that the matricellular protein CCN1/ CYR61 is highly regulated by stiffness in endothelial cells. We show that stiffness-induced CCN1 activates β-catenin nuclear translocation and signaling and that this contributes to upregulate N-cadherin levels on the surface of the endothelium, in vitro. This facilitates N-cadherin-dependent cancer cell-endothelium interaction. Using intravital imaging, we show that knockout of Ccn1 in endothelial cells inhibits melanoma cancer cell binding to the blood vessels, a critical step in cancer cell transit through the vasculature to metastasize. Targeting stiffness-induced changes in the vasculature, such as CCN1, is therefore a potential yet unappreciated mechanism to impair metastasis. [ABSTRACT FROM AUTHOR]

Consensus methods are widely used for combining phylogenetic trees into a single estimate of the evolutionary tree for a group of species. As more taxa are added, the newsource trees may begin to tell a different evolutionary story when restricted to the original set of taxa. However, if the newtrees, restricted to the original set of taxa,were to agree exactly with the earlier trees, then we might hope that their consensus would either agree with or resolve the original consensus tree. In this article,we ask under what conditions consensus methods exist that are "future proof" in this sense. Whilewe showthat some methods (e.g., Adams consensus) have this property for specific types of input, we also establish a rather surprising "no-go" theorem: there is no "reasonable" consensus method that satisfies the future-proofing property in general.We then investigate a second notion of "future proofing" for consensus methods, in which trees (rather than taxa) are added, and establish some positive and negative results. We end with some questions for future work. [ABSTRACT FROM AUTHOR]

Split networks are a popular tool for the analysis and visualization of complex evolutionary histories. Every collection of splits (bipartitions) of a finite set can be represented by a split network. Here we characterize which collection of splits can be represented using a planar split network. Our main theorem links these collections of splits with oriented matroids and arrangements of lines separating points in the plane. As a consequence of our main theorem, we establish a particularly simple characterization of maximal collections of these splits. [ABSTRACT FROM AUTHOR]

The formation of distinct subdomains of the cell surface is crucial for multicellular organism development. The most striking example of this is apical-basal polarization. What is much less appreciated is that underpinning an asymmetric cell surface is an equally dramatic intracellular endosome rearrangement. Here, we review the interplay between classical cell polarity proteins and membrane trafficking pathways, and discuss how this marriage gives rise to cell polarization. We focus on those mechanisms that regulate apical polarization, as this is providing a number of insights into how membrane traffic and polarity are regulated at the tissue level. [ABSTRACT FROM AUTHOR]

We describe here experiments which demonstrate the selective phospho-transfer from a plausibly prebiotic condensed phosphorus (P) salt, pyrophosphite [HPO ; PPi(III)], to the phosphate group of 5′-adenosine mono phosphate (5′-AMP). We show further that this P-transfer process is accelerated both by divalent metal ions (M) and by organic co-factors such as acetate (AcO). In this specific case of P-transfer from PPi(III) to 5′-AMP, we show a synergistic enhancement of transfer in the combined presence of M & AcO. Isotopic labelling studies demonstrate that hydrolysis of the phosphonylated 5′-AMP, [P(III)P(V)-5′-AMP], proceeds via nuceophilic attack of water at the Pi(III) terminus. [ABSTRACT FROM AUTHOR]

Context: Extracorporeal shockwave lithotripsy (SWL) is the first-line treatment for renal calculi in most cases. Recent technology has allowed lithotriptor machines to localize stones using fluoroscopy or ultrasound (US). Aim: The aim of this study is to compare stone free rates (SFR) using two techniques. Methods: This is a single center retrospective cohort study. We have studied 95 patients with renal calculi undergoing first SWL treatment with localization using US (48 pts) and fluoroscopy (47 pts). SFR was defined as fragments ≤2 m at 4 weeks post procedure on x-ray or US. Patient records were reviewed. Results: Stone size and location, age and body mass index were comparable between groups. Stones ≤7 mm had better SFR with US 86% (18/21) compared to fluoroscopy 59% (10/17) P = 0.08. Overall the US group had similar SFR to the fluoroscopy group for stones of all sizes and locations with 60% (29/48) compared to 45% (21/47) P = 0.18. Radiation exposure was the biggest difference between techniques with a mean radiation dose (mGy/cm2) in the US group of 103 (0-233) and 2113 (241-7821) in the fluoroscopy group. Radiation use in the US group was due to the use of a single shot pre-and post-procedure, this could be reduced to zero. Conclusions: Our data show equivalent outcomes using US compared to the traditional fluoroscopy localization technique. We would encourage departments to develop the use of US localization to reduce radiation exposure to patients. [ABSTRACT FROM AUTHOR]

Monophyletic groups--groups that consist of all of the descendants of a most recent common ancestor--arise naturally as a consequence of descent processes that result in meaningful distinctions between organisms. Aspects of monophyly are therefore central to fields that examine and use genealogical descent. In particular, studies in conservation genetics, phylogeography, population genetics, species delimitation, and systematics can all make use of mathematical predictions under evolutionary models about features of monophyly. One important calculation, the probability that a set of gene lineages is monophyletic under a two-species neutral coalescent model, has been used in many studies. Here, we extend this calculation for a species treemodel that contains arbitrarilymany species. We study the effects of species tree topology and branch lengths on the monophyly probability. These analyses reveal new behavior, including the maintenance of nontrivial monophyly probabilities for gene lineage samples that span multiple species and even for lineages that do not derive from a monophyletic species group. We illustrate the mathematical results using an example application to data from maize and teosinte. [ABSTRACT FROM AUTHOR]

We present an efficient and flexible method for computing likelihoods for phenotypic traits on a phylogeny. The method does not resort to Monte Carlo computation but instead blends Felsenstein's discrete character pruning algorithm with methods for numerical quadrature. It is not limited to Gaussian models and adapts readily to model uncertainty in the observed trait values. Wedemonstrate the frame work by developing efficient algorithms for likelihood calculation and ancestral state reconstruction under Wright's threshold model, applying our methods to a data set of trait data for extrafloral nectaries across a phylogeny of 839 Fabales species. [ABSTRACT FROM AUTHOR]

Objective: To evaluate clinical outcomes of women with singleton pregnancies that underwent intra-amniotic dye instillation (amniodye test) following equivocal diagnosis of prelabor rupture of membranes (PROM).Method: Records of 34 pregnant women who underwent amniodye test for equivocal PROM were reviewed. Comparisons of characteristics, amniotic fluid (AF) cultures, AF interleukin (IL)-6 concentrations, and placenta pathology results between women who tested positive and those who tested negative were performed. A sub-analysis of women who were amniodye test-negative was also performed.Results: (1) Commonest indication for amniodye test was a typical history of PROM with positive conventional tests and persistently normal AF volume, (2) amniodye test-positive women had a shorter procedure-to-delivery interval (p = 0.008), and a greater proportion of histologic acute chorioamnionitis (p = 0.04) and funisitis (p = 0.01) than amniodye-negative women, and (3) in addition to similarities to women with amniodye-positive test, amniodye test-negative women who delivered <34 weeks, had a greater proportion of women with risk for preterm birth (p = 0.04), than their counterparts who delivered between 34 0/7 and 36 6/7 weeks.Conclusion: Equivocal diagnosis of PPROM should warrant an amniodye test to avoid iatrogenic intervention in women with intact amniotic membranes. AF analysis should be performed in amniodye test-negative women. [ABSTRACT FROM AUTHOR]

Haplotype networks are an intuitive method for visualising relationships between individual genotypes at the population level., Here, we present popart, an integrated software package that provides a comprehensive implementation of haplotype network methods, phylogeographic visualisation tools and standard statistical tests, together with publication-ready figure production., popart also provides a platform for the implementation and distribution of new network-based methods - we describe one such new method, integer neighbour-joining., The software is open source and freely available for all major operating systems. [ABSTRACT FROM AUTHOR]

Simulation experiments are used widely throughout evolutionary biology and bioinformatics to compare models, promote methods, and test hypotheses. The biggest practical constraint on simulation experiments is the computational demand, particularly as the number of parameters increases. Given the extraordinary success of Monte Carlo methods for conducting inference in phylogenetics, and indeed throughout the sciences, we investigate ways in which Monte Carlo framework can be used to carry out simulation experiments more efficiently. The key idea is to sample parameter values for the experiments, rather than iterate through them exhaustively. Exhaustive analyses become completely infeasible when the number of parameters gets too large, whereas sampled approaches can fare better in higher dimensions. We illustrate the framework with applications to phylogenetics and genetic archaeology. [ABSTRACT FROM AUTHOR]

Chloroplasts arose from cyanobacteria, mitochondria arose from proteobacteria. Both organelles have conserved their prokaryotic biochemistry, but their genomes are reduced, and most organelle proteins are encoded in the nucleus. Endosymbiotic theory posits that bacterial genes in eukaryotic genomes entered the eukaryotic lineage via organelle ancestors. It predicts episodic influx of prokaryotic genes into the eukaryotic lineage, with acquisition corresponding to endosymbiotic events. Eukaryotic genome sequences, however, increasingly implicate lateral gene transfer, both from prokaryotes to eukaryotes and among eukaryotes, as a source of gene content variation in eukaryotic genomes, which predicts continuous, lineage-specific acquisition of prokaryotic genes in divergent eukaryotic groups. Here we discriminate between these two alternatives by clustering and phylogenetic analysis of eukaryotic gene families having prokaryotic homologues. Our results indicate (1) that gene transfer from bacteria to eukaryotes is episodic, as revealed by gene distributions, and coincides with major evolutionary transitions at the origin of chloroplasts and mitochondria; (2) that gene inheritance in eukaryotes is vertical, as revealed by extensive topological comparison, sparse gene distributions stemming from differential loss; and (3) that continuous, lineage-specific lateral gene transfer, although it sometimes occurs, does not contribute to long-term gene content evolution in eukaryotic genomes. [ABSTRACT FROM AUTHOR]

With the increasing use of massively parallel sequencing approaches in evolutionary biology, the need for fast and accurate methods suitable to investigate genetic structure and evolutionary history is more important than ever. We propose new distance measures for estimating genetic distances between individuals when allelic variation, gene dosage and recombination could compromise standard approaches., We present four distance measures based on single nucleotide polymorphisms (SNP) and evaluate them against previously published measures using coalescent-based simulations. Simulations were used to test (i) whether the measures give unbiased and accurate distance estimates, (ii) whether they can accurately identify the genomic mixture of hybrid individuals and (iii) whether they give precise (low variance) estimates. The effect of rate variation among genes and recombination was also investigated., The results showed that the SNP-based genpofad distance we propose appears to work well in the widest range of circumstances. It was the most accurate and precise method for estimating genetic distances and is also relatively good at estimating the genomic mixture of hybrid individuals., Our simulations provide benchmarks to compare the performance of different methods that estimate genetic distances between organisms. [ABSTRACT FROM AUTHOR]

The mechanisms that underlie the origin of major prokaryotic groups are poorly understood. In principle, the origin of both species and higher taxa among prokaryotes should entail similar mechanisms-ecological interactions with the environment paired with natural genetic variation involving lineage-specific gene innovations and lineage-specific gene acquisitions. To investigate the origin of higher taxa in archaea, we have determined gene distributions and gene phylogenies for the 267,568 protein-coding genes of 134 sequenced archaeal genomes in the context of their homologues from 1,847 reference bacterial genomes. Archaeal-specific gene families define 13 traditionally recognized archaeal higher taxa in our sample. Here we report that the origins of these 13 groups unexpectedly correspond to 2,264 group-specific gene acquisitions from bacteria. Interdomain gene transfer is highly asymmetric, transfers from bacteria to archaea are more than fivefold more frequent than vice versa. Gene transfers identified at major evolutionary transitions among prokaryotes specifically implicate gene acquisitions for metabolic functions from bacteria as key innovations in the origin of higher archaeal taxa. [ABSTRACT FROM AUTHOR]