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This article addresses the problematic perspectives of drone culture. In critiquing focus on the drone’s apparent ‘autonomy’, it argues that such devices function as part of a socio-technical network. They are relational parts of human–machine interaction that, in our changing geopolitical realities, have a powerful influence on politics, reputation and warfare. Drawing on Žižek’s conception of parallax, the article stresses the importance of culture and perception in forming the role of the drone in widening power asymmetries. It examines how perceptions of autonomy are evoked by drones, to claim that this misperception is a smokescreen that obscures the relational socio-technical realities of the drone. The article therefore argues that a more critical culture of the drone emerges by shifting the focus and perception from autonomy to anonymity. This allows us to engage more fully with the distributed agency and decision-making that define how drones are developed and deployed. Rather than focusing on the drone as a singular, fetishised, technical object, a relational approach to the drone assemblage is proposed that highlights the competing human interests that define and resist drones in global politics and culture.

Loss of skeletal muscle mass and function is a common consequence of critical illness and a range of chronic diseases, but the mechanisms by which this occurs are unclear. To identify microRNAs (miRNAs) that were increased in the quadriceps of patients with muscle wasting and to determine the molecular pathways by which they contributed to muscle dysfunction. miRNA-542-3p/5p (miR-542-3p/5p) were quantified in the quadriceps of patients with chronic obstructive pulmonary disease and intensive care unit-acquired weakness (ICUAW). The effect of miR-542-3p/5p was determined on mitochondrial function and transforming growth factor-β signaling in vitro and in vivo. miR-542-3p/5p were elevated in patients with chronic obstructive pulmonary disease but more markedly in patients with ICUAW. In vitro, miR-542-3p suppressed the expression of the mitochondrial ribosomal protein MRPS10 and reduced 12S ribosomal RNA (rRNA) expression, suggesting mitochondrial ribosomal stress. miR-542-5p increased nuclear phospho-SMAD2/3 and suppressed expression of SMAD7, SMURF1, and PPP2CA, proteins that inhibit or reduce SMAD2/3 phosphorylation, suggesting that miR-542-5p increased transforming growth factor-β signaling. In mice, miR-542 overexpression caused muscle wasting, and reduced mitochondrial function, 12S rRNA expression, and SMAD7 expression, consistent with the effects of the miRNAs in vitro. Similarly, in patients with ICUAW, the expression of 12S rRNA and of the inhibitors of SMAD2/3 phosphorylation were reduced, indicative of mitochondrial ribosomal stress and increased transforming growth factor-β signaling. In patients undergoing aortic surgery, preoperative levels of miR-542-3p/5p were positively correlated with muscle loss after surgery. Elevated miR-542-3p/5p may cause muscle atrophy in intensive care unit patients through the promotion of mitochondrial dysfunction and activation of SMAD2/3 phosphorylation.

The microRNA miR-1 is an important regulator of muscle phenotype including cardiac muscle. Down-regulation of miR-1 has been shown to occur in left ventricular hypertrophy but its contribution to right ventricular hypertrophy in pulmonary arterial hypertension are not known. Previous studies have suggested that miR-1 may suppress transforming growth factor-beta (TGF-β) signalling, an important pro-hypertrophic pathway but only indirect mechanisms of regulation have been identified. We identified the TGF-β type 1 receptor (TGF-βR1) as a putative miR-1 target. We therefore hypothesized that miR-1 and TGF-βR1 expression would be inversely correlated in hypertrophying right ventricle of rats with pulmonary arterial hypertension and that miR-1 would inhibit TGF-β signalling by targeting TGF-βR1 expression. Quantification of miR-1 and TGF-βR1 in rats treated with monocrotaline to induce pulmonary arterial hypertension showed appropriate changes in miR-1 and TGF-βR1 expression in the hypertrophying right ventricle. A miR-1-mimic reduced enhanced green fluorescent protein expression from a reporter vector containing the TGF-βR1 3'- untranslated region and knocked down endogenous TGF-βR1. Lastly, miR-1 reduced TGF-β activation of a (mothers against decapentaplegic homolog) SMAD2/3-dependent reporter. Taken together, these data suggest that miR-1 targets TGF-βR1 and reduces TGF-β signalling, so a reduction in miR-1 expression may increase TGF-β signalling and contribute to cardiac hypertrophy.

IntroductionSkeletal muscle dysfunction is a clinically important complication of pulmonary arterial hypertension (PAH). Growth/differentiation factor 15 (GDF-15), a prognostic marker in PAH, has been associated with muscle loss in other conditions. We aimed to define the associations of GDF-15 and muscle wasting in PAH, to assess its utility as a biomarker of muscle loss and to investigate its downstream signalling pathway as a therapeutic target.MethodsGDF-15 levels and measures of muscle size and strength were analysed in the monocrotaline (MCT) rat, Sugen/hypoxia mouse and in 30 patients with PAH. In C2C12 myotubes the downstream targets of GDF-15 were identified. The pathway elucidated was then antagonised in vivo.ResultsCirculating GDF-15 levels correlated with tibialis anterior (TA) muscle fibre diameter in the MCT rat (Pearson r=−0.61, p=0.003). In patients with PAH, plasma GDF-15 levels of <564 pg/L predicted those with preserved muscle strength with a sensitivity and specificity of ≥80%. In vitro GDF-15 stimulated an increase in phosphorylation of TGFβ-activated kinase 1 (TAK1). Antagonising TAK1, with 5(Z)-7-oxozeaenol, in vitro and in vivo led to an increase in fibre diameter and a reduction in mRNA expression of atrogin-1 in both C2C12 cells and in the TA of animals who continued to grow. Circulating GDF-15 levels were also reduced in those animals which responded to treatment.ConclusionsCirculating GDF-15 is a biomarker of muscle loss in PAH that is responsive to treatment. TAK1 inhibition shows promise as a method by which muscle atrophy may be directly prevented in PAH.Trial registration numberNCT01847716; Results.

Background Loss of muscle mass is a co‐morbidity common to a range of chronic diseases including chronic obstructive pulmonary disease (COPD). Several systemic features of COPD including increased inflammatory signalling, oxidative stress, and hypoxia are known to increase the expression of growth differentiation factor‐15 (GDF‐15), a protein associated with muscle wasting in other diseases. We therefore hypothesized that GDF‐15 may contribute to muscle wasting in COPD. Methods We determined the expression of GDF‐15 in the serum and muscle of patients with COPD and analysed the association of GDF‐15 expression with muscle mass and exercise performance. To determine whether GDF‐15 had a direct effect on muscle, we also determined the effect of increased GDF‐15 expression on the tibialis anterior of mice by electroporation. Results Growth differentiation factor‐15 was increased in the circulation and muscle of COPD patients compared with controls. Circulating GDF‐15 was inversely correlated with rectus femoris cross‐sectional area (P < 0.001) and exercise capacity (P < 0.001) in two separate cohorts of patients but was not associated with body mass index. GDF‐15 levels were associated with 8‐oxo‐dG in the circulation of patients consistent with a role for oxidative stress in the production of this protein. Local over‐expression of GDF‐15 in mice caused wasting of the tibialis anterior muscle that expressed it but not in the contralateral muscle suggesting a direct effect of GDF‐15 on muscle mass (P < 0.001). Conclusions Together, the data suggest that GDF‐15 contributes to the loss of muscle mass in COPD.

Background Dexamethasone suppressed inflammation and haemodynamic changes in an animal model of pulmonary arterial hypertension (PAH). A major target for dexamethasone actions is NF-κB, which is activated in pulmonary vascular cells and perivascular inflammatory cells in PAH. Reverse remodelling is an important concept in PAH disease therapy, and further to its anti-proliferative effects, we sought to explore whether dexamethasone augments pulmonary arterial smooth muscle cell (PASMC) apoptosis. Methods Analysis of apoptosis markers (caspase 3, in-situ DNA fragmentation) and NF-κB (p65 and phospho-IKK-α/β) activation was performed on lung tissue from rats with monocrotaline (MCT)-induced pulmonary hypertension (PH), before and after day 14–28 treatment with dexamethasone (5 mg/kg/day). PASMC were cultured from this rat PH model and from normal human lung following lung cancer surgery. Following stimulation with TNF-α (10 ng/ml), the effects of dexamethasone (10 −8 –10 −6  M) and IKK2 (NF-κB) inhibition (AS602868, 0–3 μM (0-3×10 −6  M) on IL-6 and CXCL8 release and apoptosis was determined by ELISA and by Hoechst staining. NF-κB activation was measured by TransAm assay. Results Dexamethasone treatment of rats with MCT-induced PH in vivo led to PASMC apoptosis as displayed by increased caspase 3 expression and DNA fragmentation. A similar effect was seen i n vitro using TNF-α-simulated human and rat PASMC following both dexamethasone and IKK2 inhibition. Increased apoptosis was associated with a reduction in NF-κB activation and in IL-6 and CXCL8 release from PASMC. Conclusions Dexamethasone exerted reverse-remodelling effects by augmenting apoptosis and reversing inflammation in PASMC possibly via inhibition of NF-κB. Future PAH therapies may involve targeting these important inflammatory pathways.

Studies were undertaken to examine any role for the hepcidin/ferroportin axis in proliferative responses of human pulmonary artery smooth muscle cells (hPASMCs). Entirely novel findings have demonstrated the presence of ferroportin in hPASMCs. Hepcidin treatment caused increased proliferation of these cells most likely by binding ferroportin resulting in internalisation and cellular iron retention. Cellular iron content increased with hepcidin treatment. Stabilisation of ferroportin expression and activity via intervention with the therapeutic monoclonal antibody LY2928057 reversed proliferation and cellular iron accumulation. Additionally, IL-6 treatment was found to enhance proliferation and iron accumulation in hPASMCs; intervention with LY2928057 prevented this response. IL-6 was also found to increase hepcidin transcription and release from hPASMCs suggesting a potential autocrine response. Hepcidin or IL-6 mediated iron accumulation contributes to proliferation in hPASMCs; ferroportin mediated cellular iron excretion limits proliferation. Haemoglobin also caused proliferation of hPASMCs; in other novel findings, CD163, the haemoglobin/haptoglobin receptor, was found on these cells and offers a means for cellular uptake of iron via haemoglobin. Il-6 was also found to modulate CD163 on these cells. These data contribute to a better understanding of how disrupted iron homeostasis may induce vascular remodelling, such as in pulmonary arterial hypertension.

The microRNA miR-1 is an important regulator of muscle phenotype including cardiac muscle. Down-regulation of miR-1 has been shown to occur in left ventricular hypertrophy but its contribution to right ventricular hypertrophy in pulmonary arterial hypertension are not known. Previous studies have suggested that miR-1 may suppress transforming growth factor-beta (TGF-[beta]) signalling, an important pro-hypertrophic pathway but only indirect mechanisms of regulation have been identified. We identified the TGF-[beta] type 1 receptor (TGF-[beta]R1) as a putative miR-1 target. We therefore hypothesized that miR-1 and TGF-[beta]R1 expression would be inversely correlated in hypertrophying right ventricle of rats with pulmonary arterial hypertension and that miR-1 would inhibit TGF-[beta] signalling by targeting TGF-[beta]R1 expression. Quantification of miR-1 and TGF-[beta]R1 in rats treated with monocrotaline to induce pulmonary arterial hypertension showed appropriate changes in miR-1 and TGF-[beta]R1 expression in the hypertrophying right ventricle. A miR-1-mimic reduced enhanced green fluorescent protein expression from a reporter vector containing the TGF-[beta]R1 3'- untranslated region and knocked down endogenous TGF-[beta]R1. Lastly, miR-1 reduced TGF-[beta] activation of a (mothers against decapentaplegic homolog) SMAD2/3-dependent reporter. Taken together, these data suggest that miR-1 targets TGF-[beta]R1 and reduces TGF-[beta] signalling, so a reduction in miR-1 expression may increase TGF-[beta] signalling and contribute to cardiac hypertrophy.

Cute videos are everywhere online. Many of these videos increasingly come from footage taken by doorbell cameras. Amazon’s Ring, and related connected camera devices, introduce new sociotechnical relations into domestic environments. First, I outline “squeeveillance” as the affective and performative dimensions of cuteness within surveillance. I explore the Ring surveillant assemblage and why it needs the power of cuteness. Then, I examine squeeveillance as the use of cuteness in the way Ring operates. I use the TV show Ring Nation (2022–present) to discuss the remediation of cute footage from doorbell cameras onto other media, before discussing the ways in which cuteness is performed as a normalisation of surveillance power. The article draws on theories of cuteness in conjunction with surveillance studies of power relations. In presenting squeeveillance as a lens through which to assess the expanding scope of Ring, I offer a discussion of the interconnected role of surveillance in contemporary domestic and media settings and its relation to current forms of power in surveillant assemblages.

Pulmonary arterial hypertension (PAH) is characterised by remodelling of the pulmonary vasculature leading to right ventricular hypertrophy. Here, we show that miR‐322‐5p (the rodent orthologue of miR‐424‐5p) expression is decreased in the right ventricle of monocrotaline‐treated rats, a model of PAH, whereas a putative target insulin‐like growth factor 1 (IGF‐1) is increased. IGF‐1 mRNA was enriched 16‐fold in RNA immunoprecipitated with Ago2, indicating binding to miR‐322‐5p. In cell transfection experiments, miR‐322‐5p suppressed the activity of a luciferase reporter containing a section of the IGF‐1 3′ untranslated region (UTR) as well as IGF‐1 mRNA and protein levels. Taken together, these data suggest that miR‐322 targets IGF‐1, a process downregulated in PAH‐related RV hypertrophy. miRNA regulate various cell processes, which often go awry in disease. Here, we look at miR‐322‐5p, a miRNA downregulated in the hypertrophying right ventricle of rats with drug‐induced pulmonary arterial hypertension (PAH). Concomitantly, IGF‐1 is upregulated in these enlarged right ventricles. We confirmed that miR‐322‐5p targets IGF‐1, raising the possibility that reduced miR‐322‐5p contributes to the development of hypertrophy in PAH. By Mariana Ruiz [Public domain], via Wikimedia Commons.