Wild canids and felids differ in their reliance on reused travel routeways

Diverse factors, including environmental features and cognitive processes, can drive animals’ movements and space use, with far-reaching implications. For example, repeated use of individual-level travel routeways (directionally constrained but imperfectly aligned routes), which results in spatial concentration of activity, can shape encounter-based processes including predation, mate finding, and disease transmission. However, how much variation in routeway usage exists across species remains unknown. By analyzing GPS movement tracks for 1,239 range-resident mammalian carnivores—representing 16 canid and 18 felid species from six continents—we found strong evidence of a clade-level difference in species’ reliance on repeatedly used travel routeways. Across the global dataset, tracked canids had a 15% (±7 CI) greater density of routeways within their home ranges than did felids, rising to 33% (±16 CI) greater in landscapes shared with tracked felids. Moreover, comparisons within species across landscapes revealed broadly similar home range routeway densities despite habitat differences. On average, canids also reused their travel routeways more intensively than did felids, with hunting strategies and spatial contexts also contributing to the intensity of routeway usage. Collectively, our results suggest that key aspects of carnivore routeway-usage have an evolutionary component. Striking interspecific and clade-level differences in carnivores’ reliance on reused travel routeways within home ranges identify important ways in which the movement patterns of real-world predators depart from classical assumptions of predator-prey theory. Because such departures can drive key aspects of human-wildlife interactions and other encounter-based processes, continued investigations of the relationships between movement mechanisms and space use are critical

In vivo imaging of nanoparticle-labeled CAR T cells

Significance Chimeric antigen receptor (CAR) T-cell therapy is approved by the US Food and Drug Administration (FDA) for the treatment of B-cell acute lymphoblastic leukemia. Efforts are now underway to evaluate the efficacy of CAR T-cell therapy in solid tumors. However, a key limitation in the advancement of T-cell therapy is the lack of information on the biodistribution of the T cells in patients. Therefore, there is a need for the identification of translatable methods for tracking the therapeutic T cells noninvasively. We describe the mechanical labeling of CAR T cells with an FDA-approved iron oxide nanoparticle to demonstrate the noninvasive and multimodal imaging of the CAR T cells. This method may be utilized for monitoring T cells in clinical trials.</jats:p

Engineered CD47 protects T cells for enhanced antitumour immunity

Adoptively transferred T cells and agents designed to block the CD47-SIRPα axis are promising cancer therapeutics that activate distinct arms of the immune system . Here we administered anti-CD47 antibodies in combination with adoptively transferred T cells with the goal of enhancing antitumour efficacy but observed abrogated therapeutic benefit due to rapid macrophage-mediated clearance of T cells expressing chimeric antigen receptors (CARs) or engineered T cell receptors. Anti-CD47-antibody-mediated CAR T cell clearance was potent and rapid enough to serve as an effective safety switch. To overcome this challenge, we engineered the CD47 variant CD47(Q31P) (47 ), which engages SIRPα and provides a 'don't eat me' signal that is not blocked by anti-CD47 antibodies. TCR or CAR T cells expressing 47 are resistant to clearance by macrophages after treatment with anti-CD47 antibodies, and mediate substantial, sustained macrophage recruitment to the tumour microenvironment. Although many of the recruited macrophages manifested an M2-like profile , the combined therapy synergistically enhanced antitumour efficacy. Our study identifies macrophages as major regulators of T cell persistence and illustrates the fundamental challenge of combining T-cell-directed therapeutics with those designed to activate macrophages. It delivers a therapeutic approach that is capable of simultaneously harnessing the antitumour effects of T cells and macrophages, offering enhanced potency against solid tumours

Public-to-Private Transactions: LBOs, MBOs, MBIs and IBOs

This paper shows that a vibrant and economically important public-to-private market has reemerged in the US, UK and Continental Europe, since the second half of the 1990s.The paper shows recent trends and investigates the motives for public-to-private and LBO transactions.The reasons for the potential sources of shareholder wealth effects during the transaction period are examined: a distinction is made between tax benefits, incentive realignment, transaction costs savings, stakeholder expropriation, takeover defenses and corporate undervaluation.The paper also attempts to relate these value drivers to the post-transaction value and to the duration of the private status.Finally, the paper draws some conclusions about whether or not public-to-private transactions are useful devices for corporate restructuring.

A comprehensive transcriptional map of primate brain development.

The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high-resolution transcriptional atlas of rhesus monkey (Macaca mulatta) brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical division of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons. Cortical layers and areas acquire adult-like molecular profiles surprisingly late in postnatal development. Disparate cell populations exhibit distinct developmental timing of gene expression, but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, although approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny compared to monkey

A comprehensive transcriptional map of primate brain development

The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high resolution transcriptional atlas of rhesus monkey brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical parcellation of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons, and cortical layers and areas acquire adult-like molecular profiles surprisingly late postnatally. Disparate cell populations exhibit distinct developmental timing but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, and approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny