ABSTRACT
OJ 287 is a BL Lacertae type quasar in which the active galactic nucleus (AGN) outshines the host galaxy by an order of magnitude. The only exception to this may be at minimum light when the ...AGN activity is so low that the host galaxy may make quite a considerable contribution to the photometric intensity of the source. Such a dip or a fade in the intensity of OJ 287 occurred in 2017 November, when its brightness was about 1.75 mag lower than the recent mean level. We compare the observations of this fade with similar fades in OJ 287 observed earlier in 1989, 1999, and 2010. It appears that there is a relatively strong reddening of the B− V colours of OJ 287 when its V-band brightness drops below magnitude 17. Similar changes are also seen in V− R, V− I, and R− I colours during these deep fades. These data support the conclusion that the total magnitude of the host galaxy is V = 18.0 ± 0.3, corresponding to MK = −26.5 ± 0.3 in the K-band. This is in agreement with the results, obtained using the integrated surface brightness method, from recent surface photometry of the host. These results should encourage us to use the colour separation method also in other host galaxies with strongly variable AGN. In the case of OJ 287, both the host galaxy and its central black hole are among the biggest known, and its position in the black hole mass–galaxy mass diagram lies close to the mean correlation.
Pathological neovessel formation impacts many blinding vascular eye diseases. Identification of molecular signatures distinguishing pathological neovascularization from normal quiescent vessels is ...critical for developing new interventions. Twist-related protein 1 (TWIST1) is a transcription factor important in tumor and pulmonary angiogenesis. This study investigated the potential role of TWIST1 in modulating pathological ocular angiogenesis in mice.
Twist1 expression and localization were analyzed in a mouse model of oxygen-induced retinopathy (OIR). Pathological ocular angiogenesis in Tie2-driven conditional Twist1 knockout mice were evaluated in both OIR and laser-induced choroidal neovascularization models. In addition, the effects of TWIST1 on angiogenesis and endothelial cell function were analyzed in sprouting assays of aortic rings and choroidal explants isolated from Twist1 knockout mice, and in human retinal microvascular endothelial cells treated with TWIST1 small interfering RNA (siRNA).
TWIST1 is highly enriched in pathological neovessels in OIR retinas. Conditional Tie2-driven depletion of Twist1 significantly suppressed pathological neovessels in OIR without impacting developmental retinal angiogenesis. In a laser-induced choroidal neovascularization model, Twist1 deficiency also resulted in significantly smaller lesions with decreased vascular leakage. In addition, loss of Twist1 significantly decreased vascular sprouting in both aortic ring and choroid explants. Knockdown of TWIST1 in endothelial cells led to dampened expression of vascular endothelial growth factor receptor 2 (VEGFR2) and decreased endothelial cell proliferation.
Our study suggests that TWIST1 is a novel regulator of pathologic ocular angiogenesis and may represent a new molecular target for developing potential therapeutic treatments to suppress pathological neovascularization in vascular eye diseases.
We report the properties of a draft genome sequence of the bacterium Arsenophonus nasoniae, son-killer bacterium of Nasonia vitripennis. The genome sequence data from this study are the first for a ...male-killing bacterium, and represent a microorganism that is unusual compared with other sequenced symbionts, in having routine vertical and horizontal transmission, two alternating hosts, and being culturable on cell-free media. The resulting sequence totals c. 3.5 Mbp and is annotated to contain 3332 predicted open reading frames (ORFs). Therefore, Arsenophonus represents a relatively large genome for an insect symbiont. The annotated ORF set suggests that the microbe is capable of a broad array of metabolic functions, well beyond those found for reproductive parasite genomes sequenced to date and more akin to horizontally transmitted and secondary symbionts. We also find evidence of genetic transfer from Wolbachia symbionts, and phage exchange with other gammaproteobacterial symbionts. These findings reflect the complex biology of a bacterium that is able to live, invade and survive multiple host environments while resisting immune responses.
Maternally inherited symbionts are common in arthropods and many have important roles in host adaptation. The observation that specific symbiont lineages infect distantly related host species implies ...new interactions are commonly established by lateral transfer events. However, studies have shown that symbionts often perform poorly in novel hosts. We hypothesized selection on the symbiont may be sufficiently rapid that poor performance in a novel host environment is rapidly ameliorated, permitting symbiont maintenance. Here, we test this prediction for a Spiroplasma strain transinfected into the novel host Drosophila melanogaster. In the generations immediately following transinfection, the symbiont had low transmission efficiency to offspring and imposed severe fitness costs on its host. We observed that effects on host fitness evolved rapidly, being undetectable after 17 generations in the novel host, whereas vertical transmission efficiency was poorly responsive over this period. Our results suggest that long-term symbiosis may more readily be established in cases where symbionts perform poorly in just one aspect of symbiosis.
This unique history of Japanese armed martial arts-the only comprehensive treatment of the subject in English-focuses on traditions of swordsmanship and archery from ancient times to the present. G. ...Cameron Hurst III provides an overview of martial arts in Japanese history and culture, then closely examines the transformation of these fighting skills into sports. He discusses the influence of the Western athletic tradition on the armed martial arts as well as the ways the martial arts have remained distinctly Japanese.During the Tokugawa era (1600-1867), swordsmanship and archery developed from fighting systems into martial arts, transformed by the powerful social forces of peace, urbanization, literacy, and professionalized instruction in art forms. Hurst investigates the changes that occurred as military skills that were no longer necessary took on new purposes: physical fitness, spiritual composure, character development, and sport. He also considers Western misperceptions of Japanese traditional martial arts and argues that, contrary to common views in the West, Zen Buddhism is associated with the martial arts in only a limited way. The author concludes by exploring the modern organization, teaching, ritual, and philosophy of archery and swordsmanship; relating these martial arts to other art forms and placing them in the broader context of Japanese culture.
Much of our understanding of female mating behaviour in insects comes from studies performed under controlled laboratory conditions, with
Drosophila as the most commonly used model system. Laboratory ...studies of
Drosophila have demonstrated a strong genetic basis to female remating rate. Because behaviour is strongly influenced by the environment, the heritability of remating rate in laboratory cultures does not necessarily reflect variation that is relevant to field conditions. In this study, we investigated the strength of the link between the behaviour of flies in laboratory and field. Wild-caught female
Drosophila pseudoobscura that produced broods sired by multiple males had daughters that remated more rapidly in the laboratory. This suggests that laboratory experiments can successfully reflect differences between females’ mating behaviour in nature.
► We examine fruit fly mating in nature and that of their daughters in the laboratory. ► We find polyandry in nature correlates with faster remating by daughters in the lab. ► Hence lab studies capture important differences in mating behaviour seen in nature. ► This implies there is strong genetic control of female remating in the wild.
Inflammatory cytokines and growth factors drive angiogenesis independently; however, their integrated role in pathologic and physiologic angiogenesis is not fully understood. Suppressor of cytokine ...signaling-3 (SOCS3) is an inducible negative feedback regulator of inflammation and growth factor signaling. In the present study, we show that SOCS3 curbs pathologic angiogenesis. Using a Cre/Lox system, we deleted SOCS3 in vessels and studied developmental and pathologic angiogenesis in murine models of oxygen-induced retinopathy and cancer. Conditional loss of SOCS3 leads to increased pathologic neovascularization, resulting in pronounced retinopathy and increased tumor size. In contrast, physiologic vascularization is not regulated by SOCS3. In vitro, SOCS3 knockdown increases proliferation and sprouting of endothelial cells costimulated with IGF-1 and TNFα via reduced feedback inhibition of the STAT3 and mTOR pathways. These results identify SOCS3 as a pivotal endogenous feedback inhibitor of pathologic angiogenesis and a potential therapeutic target acting at the converging crossroads of growth factor– and cytokine-induced vessel growth.
Health inequalities are a major concern in the UK. Power imbalances are associated with health inequalities and should be challenged through health promotion and empowering strategies, enabling ...individuals who feel powerless to take control over their own life and act on the determinants of health (Green and Tones, 2010). This study aimed to explore resident expectations of a community engagement programme that intended to empower communities to take action on pre-identified priorities. The programme targeted communities in deprived areas of a mid-sized city in the UK.
A qualitative design was implemented. In-depth semi-structured interviews were undertaken with 28 adult residents at the start of the programme. Transcripts were analysed using an inductive approach to thematic analysis. Resident expectations were explored from a constructivist epistemological perspective. The qualitative inductive approach allowed a second research question to develop which led this paper to focus on exploring how disempowerment was experienced by individuals before taking part in a community engagement programme.
Analysis of interviews revealed a ‘process of deterioration’ that provided insight into how communities might become (more) disadvantaged through disempowerment. Five master themes were identified: external abandonment at the institutional-level (master theme 1); a resulting loss of sense of community (master theme 2); this negatively affected psychological wellbeing of residents (master theme 3); who adopted coping strategies (e.g., disengagement) to aid living in such challenging areas; (master theme 4); disengagement further perpetuated the deterioration of the area (master theme 5). Distrust was identified as a major barrier to participation in community engagement programmes.
Overall, our data suggested that community engagement approaches must prioritise restoration of trust and be accompanied by supportive policies to mitigate feelings of abandonment in communities.
•Institutional-level disempowerment can explain community disengagement and distrust.•Social isolation can evolve as a coping strategy to deal with life in disadvantaged areas.•Restoring trust on professionals and statutory organisations should be the first priority of community engagement programmes.
Water-soluble glass patterned by 3D printing is a versatile tool for tissue engineering and microfluidics. Glasses can be patterned layer-by-layer as in conventional fused deposition modeling but ...also along 3D, “freeform” paths. In the latter approach, extruding heated material through a nozzle translating in 3D space allows for fabrication of sparse, freestanding networks of cylindrical filaments. These freeform structures are suitable for sacrificial molding with a variety of media, leaving complex microchannel networks. However, 3D printing carbohydrate glass in this way presents several unique challenges: 1) the material must resist degradation and crystallization during printing, 2) the glass must be hot enough to flow freely during extrusion and fuse to the printed construct, while cooling rapidly to retain its shape upon exiting the nozzle, 3) the extruder needs to apply high pressure, with rapid stop and start times and 4) the net force that acts on the filament during extrusion must be minimized so that the filament shape is predictable, i.e., coincides with the path taken by the nozzle. First, we review the properties of commercially available carbohydrate glasses and provide a guide for processing isomalt, our material of choice, to achieve the best printing performance. A pressure-controlled, piston-driven extruder is then described which allows for rapid responses and precise control over the material flow rate. We then analyze the heat transfer within the filament and the forces that contribute to the filament’s final shape. We find that the dominant force is due to the radial flow of the molten glass as it exits the nozzle. This analysis is validated on a purpose-built isomalt 3D printer, which we utilize to characterize relationships between extrusion pressure, translation speed, filament diameter, and viscous force. The insights of the physics of the printing process enable fabrication of intricate freeform prints as well as layer-by-layer designs. The practical and theoretical considerations should facilitate adoption of additive manufacturing of carbohydrate glasses with applications to a wide variety of fields, including tissue engineering and microfluidics.
Retinopathy of prematurity (ROP) is a leading cause of blindness in children and is, in its most severe form, characterized by uncontrolled growth of vision-threatening pathologic vessels. ...Propranolol, a nonselective β-adrenergic receptor blocker, was reported to protect against pathologic retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). Based on this single animal study using nonstandard evaluation of retinopathy, clinical trials are currently ongoing to evaluate propranolol treatment in stage 2 ROP patients who tend to experience spontaneous disease regression and are at low risk of blindness. Because these ROP patients are vulnerable premature infants who are still in a fragile state of incomplete development, the efficacy of propranolol treatment in retinopathy needs to be evaluated thoroughly in preclinical animal models of retinopathy and potential benefits weighed against potential adverse effects.
Retinopathy was induced by exposing neonatal mice to 75% oxygen from postnatal day (P) 7 to P12. Three routes of propranolol treatment were assessed from P12 to P16: oral gavage, intraperitoneal injection, or subcutaneous injection, with doses varying between 2 and 60 mg/kg/day. At P17, retinal flatmounts were stained with isolectin and quantified with a standard protocol to measure vasoobliteration and pathologic neovascularization. Retinal gene expression was analyzed with qRT-PCR using RNA isolated from retinas of control and propranolol-treated pups.
None of the treatment approaches at any dose of propranolol (up to 60 mg/kg/day) were effective in preventing the development of retinopathy in a mouse model of OIR, evaluated using standard techniques. Propranolol treatment also did not change retinal expression of angiogenic factors including vascular endothelial growth factor.
Propranolol treatment via three routes and up to 30 times the standard human dose failed to suppress retinopathy development in mice. These data bring into question whether propranolol through inhibition of β-adrenergic receptors is an appropriate therapeutic approach for treating ROP.
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