Arp2/3 Complex Is Required for Macrophage Integrin Functions but Is Dispensable for FcR Phagocytosis and In Vivo Motility

The Arp2/3 complex nucleates branched actin, forming networks involved in lamellipodial protrusion, phagocytosis, and cell adhesion. We derived primary bone marrow macrophages lacking Arp2/3 complex (Arpc2−/−) and directly tested its role in macrophage functions. Despite protrusion and actin assembly defects, Arpc2−/− macrophages competently phagocytose via FcR and chemotax toward CSF and CX3CL1. However, CR3 phagocytosis and fibronectin haptotaxis, both integrin-dependent processes, are disrupted. Integrin-responsive actin assembly and αM/β2 integrin localization are compromised in Arpc2−/− cells. Using an in vivo system to observe endogenous monocytes migrating toward full-thickness ear wounds we found that Arpc2−/− monocytes maintain cell speeds and directionality similar to control. Our work reveals that the Arp2/3 complex is not a general requirement for phagocytosis or chemotaxis but is a critical driver of integrin-dependent processes. We demonstrate further that cells lacking Arp2/3 complex function in vivo remain capable of executing important physiological responses that require rapid directional motility. Using a combination of cell culture-based and in vivo mouse experiments, Rotty et al. demonstrate that the actin-nucleating Arp2/3 complex is not absolutely required for macrophage FcR phagocytosis, chemotaxis, or in vivo monocyte directional motility. Rather, the complex has a critical role in regulating integrin-dependent macrophage processes

Expectations and beliefs: How single young gay, bisexual and other men who have sex with men envision romantic relationships

We developed measures of relational beliefs and expectations among single young gay and bisexual men (YGBM). Data come from an online cross-sectional study YGBM, which ran from July 2012 until January 2013. There were 50 items on relational beliefs and 25 items on relational expectations. We used random split samples and a priori analysis to group items together and applied principal axis factoring with varimax orthogonal rotation. We had a total N = 1582 in our analytical sample and identified six constructs of relational expectations (restrictions, negative break up, masculine and gender norms, optimism, cheating, immediacy) and two constructs of relational beliefs (sex beliefs, equality). Our findings highlight specific relational cognitions among YGBM and offer insight into the beliefs and expectations that may inform their relationships. Findings may be useful for health professionals to help YGBM reflect and understand the health implications of their beliefs and expectations about same-sex relationships to promote healthy decision-making as they seek future partners

Anatomical origins of ocular dominance in mouse primary visual cortex

Ocular dominance (OD) plasticity is a classic paradigm for studying the effect of experience and deprivation on cortical development, and is manifested as shifts in the relative strength of binocular inputs to primary visual cortex (V1). The mouse has become an increasingly popular model for mechanistic studies of OD plasticity and, consequently, it is important that we understand how binocularity is constructed in this species. One puzzling feature of the mouse visual system is the gross disparity between the physiological strength of each eye in V1 and their anatomical representation in the projection from retina to the dorsal lateral geniculate nucleus (dLGN). While the contralateral-to-ipsilateral (C/I) ratio of visually evoked responses in binocular V1 is approximately 2:1, the ipsilateral retinal projection is weakly represented in terms of retinal ganglion cell (RGC) density where the C/I ratio is approximately 9:1. The structural basis for this relative amplification of ipsilateral eye responses between retina and V1 is not known. Here we employed neuroanatomical tracing and morphometric techniques to quantify the relative magnitude of each eye's input to and output from the binocular segment of dLGN. Our data are consistent with the previous suggestion that a point in space viewed by both eyes will activate 9 times as many RGCs in the contralateral retina as in the ipsilateral retina. Nonetheless, the volume of the dLGN binocular segment occupied by contralateral retinogeniculate inputs is only 2.4 times larger than the volume occupied by ipsilateral retinogeniculate inputs and recipient relay cells are evenly distributed among the input layers. The results from our morphometric analyses show that this reduction in input volume can be accounted for by a three-to-one convergence of contralateral eye RGC inputs to dLGN neurons. Together, our findings establish that the relative density of feed-forward dLGN inputs determines the C/I response ratio of mouse binocular V1

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

Myeloid SLC2a1-deficient murine model revealed macrophage activation and metabolic phenotype are fueled by GLUT1

Macrophages (MFs) are heterogeneous and metabolically flexible, with metabolism strongly affecting immune activation. A classic response to proinflammatory activation is increased flux through glycolysis with a downregulation of oxidative metabolism, whereas alternative activation is primarily oxidative, which begs the question of whether targeting glucose metabolism is a viable approach to control MF activation. We created a murine model of myeloid-specific glucose transporter GLUT1 (Slc2a1) deletion. Bone marrow-derived MFs (BMDM) from Slc2a1 M -/ - mice failed to uptake glucose and demonstrated reduced glycolysis and pentose phosphate pathway activity. Activated BMDMs displayed elevated metabolism of oleate and glutamine, yet maximal respiratory capacity was blunted in MF lacking GLUT1, demonstrating an incomplete metabolic reprogramming. Slc2a1 M -/ - BMDMs displayed a mixed inflammatory phenotype with reductions of the classically activated pro- and anti-inflammatory markers, yet less oxidative stress. Slc2a1 M -/ - BMDMs had reduced proinflammatory metabolites, whereas metabolites indicative of alternative activation-such as ornithine and polyamines-were greatly elevated in the absence of GLUT1. Adipose tissue MFs of lean Slc2a1 M -/ - mice had increased alternative M2-like activation marker mannose receptor CD206, yet lack of GLUT1 was not a critical mediator in the development of obesity-associated metabolic dysregulation. However, Ldlr-/ - mice lacking myeloid GLUT1 developed unstable atherosclerotic lesions. Defective phagocytic capacity in Slc2a1 M -/ - BMDMs may have contributed to unstable atheroma formation. Together, our findings suggest that although lack of GLUT1 blunted glycolysis and the pentose phosphate pathway, MF were metabolically flexible enough that inflammatory cytokine release was not dramatically regulated, yet phagocytic defects hindered MF function in chronic diseases

A circle RNA regulatory axis promotes lung squamous metastasis via CDR1-mediated regulation of golgi trafficking

Lung squamous carcinoma (LUSC) is a highly metastatic disease with a poor prognosis. Using an integrated screening approach, we found that miR-671-5p reduces LUSC metastasis by inhibiting a circular RNA (circRNA), CDR1as. Although the putative function of circRNA is through miRNA sponging, we found that miR-671-5pmore potently silenced an axis of CDR1as and its antisense transcript, cerebellar degeneration related protein 1 (CDR1). Silencing of CDR1as or CDR1 significantly inhibited LUSC metastases and CDR1 was sufficient to promote migration and metastases. CDR1, which directly interacted with adaptor protein 1 (AP1) complex subunits and coatomer protein I (COPI) proteins, no longer promoted migration upon blockade of Golgi trafficking. Therapeutic inhibition of the CDR1as/CDR1 axis with miR-671-5p mimics reduced metastasis in vivo. This report demonstrates a novel role for CDR1 in promoting metastasis and Golgi trafficking. These findings reveal an miRNA/ circRNA axis that regulates LUSC metastases through a previously unstudied protein, CDR1. Significance: This study shows that circRNA, CDR1as, promotes lung squamous migration, metastasis, and Golgi trafficking through its complimentary transcript, CDR1. Significance: This study shows that circRNA, CDR1as, promotes lung squamous migration, metastasis, and Golgi trafficking through its complimentary transcript, CDR1