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Knockout of the intracellular calcium conducting ion channel Mitsugumin 23 (MG23) protects against pressure overload induced left ventricular hypertrophy and cardiac dysfunction
No full textIn cardiac dysfunction, intracellular Ca2+-dynamics are disrupted leading to leakage of Ca2+ from the sarcoplasmic reticulum (SR). This results in diminished cardiac contractility and impaired cardiac function. In cardiac tissue, the underlying molecular mechanisms responsible for RyR2-independent Ca2+-leak are poorly understood. Mitsugumin 23 (MG23) is an intracellular Ca2+-conducting ion channel located on endoplasmic/sarcoplasmic reticulum (ER/SR) and nuclear membranes. We propose that MG23 contributes to regulation of intracellular Ca2+-homeostasis, and that altered MG23 function may drive progression of cardiac dysfunction. The aim of this research was to investigate the role of MG23 in SR Ca2+-leak, and whether knockout of Mg23 protects the heart against pressure-overload induced left ventricular hypertrophy. Cardiac pressure-overload was induced in wild type (WT) and Mg23-knockout (KO) mice through subcutaneous Angiotensin II (AngII, 1.1 mg/kg/day) infusion via osmotic pump. After 10-day infusion, in vivo pressure-volume dynamics were measured by insertion of a pressure-volume catheter into the left ventricle. MG23 protein expression was assessed through Western blot analysis. Ventricular fibrosis and cardiomyocyte size were measured using histological and immunofluorescence approaches. Cardiomyocytes were isolated from WT and Mg23-KO hearts and intracellular Ca2+-dynamics assessed through live cell imaging using the Ca2+ indicator Fluo-4. AngII-induced cardiac pressure-overload increased expression of MG23 in WT mouse hearts. Knockout of Mg23 protected hearts against AngII-induced cardiac hypertrophy. Compared to WT animals, AngII treated Mg23-KO mice displayed a significant reduction in left ventricular fibrosis and displayed normal cardiac functioning. Overexpression of MG23 in the ventricular cell line H9C2, resulted in reduced SR Ca2+ store levels. In Mg23-KO hearts, no alteration in expression of key Ca2+-handling proteins was identified, but cardiomyocytes displayed altered Ca2+-spark profiles consistent with a role for MG23 in SR Ca2+-leak. MG23 plays a key role in driving Ca2+-dysregulation observed in the early pathological stages of pressure-overload induced heart failure
Tonically active interneurons gate motor output in <i>Drosophila </i>larvae
No full textTonic inhibition and its transient removal are fundamental neural mechanisms for gating activity, suppressing out-of-phase excitation, and enhancing the temporal precision of behavior. However, their roles within locomotor central pattern generators (CPGs) remain poorly understood. Here, we identify A02l neurons-segmentally repeated excitatory interneurons in the Drosophila larval ventral nerve cord (VNC)-that regulate crawling behavior through tonic inhibition. A02l neurons exhibit high baseline activity and are transiently suppressed during motor output. They provide excitatory input to inhibitory premotor networks, enabling widespread silencing of motor neurons to maintain muscle relaxation. Optogenetic activation of A02l neurons reduced crawling frequency, whereas their inhibition induced transient whole-body contractions. Together, these findings reveal a cellular-resolution mechanism for tonic inhibition within the nerve cord and highlight its importance in gating motor output and maintaining motor quiescence.<br/
Seres planos:posthumanismo y performance en Ramón Gómez de la Serna
No full textRamón Gómez de la Serna (1888-1963) was interested in the transformation of the modern artist, including the writer, into a performer inserted into a capitalist circuit of production and consumption of artistic products. Ramón studies how the identities of the performer as artist and as individual are flattened in a confusion of private and public image typical of contem-porary celebrities. I trace these reflections in Gómez de la Serna's work, starting with his interest in Charles Chaplin and his comedy and Ramón´s Los medios seres (1929)
When resilience becomes a burden:reflections from Gazan Palestinian scholars
No full textIn this essay, Palestinian scholars from Gaza reflect on how Gaza is brought into Western academic spaces since the beginning of the genocide. Over the last two years, academic engagement with Gaza has increased, often highlighting Palestinian resilience. While this attention is essential and needed, the authors argue that framing Palestinians as resilient obscures the toll of genocidal, settler-colonial violence. This narrative not only clouds grief, exhaustion, and fragmentation, but also reassures external observers and absolves them of the responsibility to act to stop the genocide. Drawing on their lived experiences, the authors show how resilience discourse romanticizes suffering, aestheticizes sumud, and dismisses Palestinian voices as too emotional for credibility. Instead, they call for an ethical approach in academic settings that situates survival within its violent conditions, resists reductive binaries of heroism or victimhood, and centers Gaza’s lived realities in order to confirm Palestinian humanity beyond the rhetoric of resilience
Temporal changes in the dietary niche of sympatric seals provides insight into the role of competition in population declines
No full textCompetition theory suggests that interspecific prey competition can result in changes to the dietary niche, but obtaining timeseries of data from sympatric species experiencing temporal variation in competition is challenging. Scotland is an important area for two species of seals, but over the past 20 years, populations of harbour seals Phoca vitulina vitulina in some areas have declined, and competition with stable/increasing numbers of grey seals Halichoerus grypus is a potential factor. Here, we standardised disparate seal diet datasets (based on analysis of prey hard parts in faeces) to investigate summer dietary metrics in two regions spanning a 24-year period. We estimated dietary niche breadth (Simpson's diversity, D) modelled as a function of sample size, proportional biomass diet composition corrected for digestion, and interspecific dietary niche overlap (Pianka index, O). Dietary niche overlap was high across time and space (O >0.7). In the Moray Firth, the harbour seal dietary niche was narrow when the population was high and stable (1987–1995, mean ± SE, D = 2.9 ± 0.3) but was significantly broader when the population depleted (2010, D = 7.2 ± 0.5). Prey composition shifted from energy-rich sandeels and clupeids to a more diverse diet of gadids and flatfish. Conversely, the dietary niche of the stable/increasing grey seal population was consistently narrow, dominated by sandeels (e.g. 2010, D = 2.3 ± 0.4). In southeast Scotland, where grey seal numbers were stable and harbour seals declined, there was no trend in the dietary niche of either species, though sandeels were less prevalent in later years. We propose that grey seals outcompeted harbour seals in the Moray Firth, and that the availability of sandeels to both seal species decreased in southeast Scotland. Changes in prey availability have therefore likely been a factor in regional harbour seal declines and could be preventing recovery
Protocol for intraventricular injection of retinoids and hypothalamic application of viral vectors in the rat and mouse brain
No full textThe brain, specifically the hypothalamus, is a key regulator of the homeostatic balance of numerous biomolecules in the body via its control of the neuroendocrine system. Here, we present a protocol to study body vitamin A balance by injecting synthetic retinoids into the third ventricle of the rat brain. We also describe steps for the intraventricular application of viral vectors to the arcuate nucleus of a mouse brain to knock down vitamin A homeostatic genes. This approach is applicable to the study of vitamin A homeostasis. For complete details on the use and execution of this protocol, please refer to Imoesi et al.1.</p
Can animals reason?:Hobbes’s theory of nonverbal reasoning and animal reasoning
No full textThis article reconstructs Thomas Hobbes’s theory of nonverbal reasoning and examines its implications for animal cognition. While Hobbes is often read as reducing reason to verbal computation, close analysis of Leviathan, De Corpore, and earlier texts reveals a more nuanced account in which reasoning originates as the imaginative “computation” of phantasms. While acknowledging discrepancies between different works, the article emphasizes their underlying coherence and development. It argues that Hobbes recognizes a form of nonverbal animal reasoning grounded in perceptual “comparison,” though he denies animals the capacity to engage in reasoning involving mnemonic or imaginary content. This account reveals a structural continuity between human and animal logical thinking, while also highlighting the limitations of the latter. The article situates Hobbes within early modern debates on reason, prudence, and universals, showing how his radical nominalism reinforces the primacy of imagination in reasoning. In doing so, it clarifies Hobbes’s contribution to the philosophy of mind and underscores his relevance to ongoing debates about the nature and limits of animal cognition
Can provision of near vision glasses as an early intervention improve visual outcomes in infants at risk of perinatal brain insult?:the Babies in Glasses (BiG) randomised feasibility trial
No full textObjectives: We conducted a feasibility study to evaluate the feasibility of recruiting patients to examine the effect of near vision glasses in young infants at risk of cerebral visual impairment.Design: A three-arm, parallel-group, open-label randomised feasibility trial.Setting: Tertiary neonatal intensive care in London, UK.Participants: We included babies born before 29 weeks of gestation or at full term with hypoxic ischaemic encephalopathy. Babies who needed ongoing inpatient care, with established eye anomalies or with very high refractive errors at baseline (<-6.00 dioptres (D) or >±8.00D) were not included. Infants with retinopathy of prematurity were not excluded.Interventions: At 8 weeks corrected age, we allocated 18 infants to wear glasses (+3.00D over full cycloplegic refraction) immediately (intervention 1), 18 to wear the same glasses at 16 weeks (intervention 2) and 19 infants were allocated to standard treatment (no glasses).Outcomes: Recruitment and retention of study participants (primary), compliance wearing glasses, preferential-looking visual acuity (with glasses) and visual function as determined using A Test Battery of Child Development for Examining Functional Vision at 3-month and 6-month age post-term.Results: Of 70 eligible families, 55 consented and 34 attended baseline assessments, and 28 completed the study. Non-attendance was due mainly to prolonged inpatient stay, infant health and scheduling conflicts. Glasses were worn for similar periods in each group (Intervention 1: median 2 hours/day (95% CI 1 hour to 4 hours); Intervention 2: median 2 hours/day (95% CI 1.5 hours to 3 hours)). Visual acuity improved from baseline to 6 months. Mean (SE) LogMAR (Minimum Angle of Resolution) improvements were standard care: 0.47 (0.45); intervention 1: 0.66 (0.44); intervention 2: 0.37 (0.36). Among the 29 very preterm infants, there were similar findings: standard care: 0.35 (0.35); Intervention 1: 0.67 (0.47); Intervention 2: 0.34 (0.40). As a functional measure, object permanence was present at the following rates by randomised arm: standard care: 29%; whereas intervention 1: 56%; and intervention 2: 44% (OR intervention 1 vs standard care: 3.13 (95% CI 0.38 to 25.57), ie, not statistically significant).Conclusions: We demonstrate feasibility for a definitive RCT (randomized controlled trial) with good recruitment and retention and observed potential benefits for vision and development following the dispensing of glasses at 8 weeks post-term age compared with untreated controls. We identified methodological modifications to further improve recruitment processes for a future larger study.</p
Introduction:Austria and film in the twenty-first century
No full textIn 2006, Dennis Lim wrote that the propensity of recent films from Austria to focus on the 'negative and the abject' had made 'this tiny country […] something like the world capital of feel-bad cinema'. His provocation has since been so frequently invoked in discussions of contemporary Austrian film that it has become something of a cliché, whether to be challenged or confirmed. The late Frederick Baker, in his 2020 film essay Cinema Austria—Die ersten 112 Jahre [Cinema Austria—The First 112 Years], goes one step further, claiming that filmmakers now wear this seemingly negative label as a badge of pride. Interviews with three of the country's most prominent directors serve to prove his point. Barbara Albert thinks 'feel-bad movie' is an amusing expression ('lustiger Ausdruck'); it has something charming about it and implies comedy and humour. Jessica Hausner, meanwhile, says that it is actually feel-good movies that make her feel bad and the so-called feel-bad element of Austrian films is a source of huge relief for her: finally someone else is prepared to show things—the horror of dying, for example—as they really are, and she realizes she is not the only person with such preoccupations. Michael Haneke, while on the one hand dismissing the term as 'blöd' [stupid], sees it, on the other, as a 'positives Charakteristikum' [positive characteristic]; filmmakers are prepared to recognize that the world is far from 'in Ordnung' [all right]. In this way, feel-bad cinema is an important counter to filmic attempts to portray reality otherwise, attempts that, according to Haneke would only be made by liars, idiots, or cynics. Lim's descriptor can and has been dismissed as reductive and, as Robert von Dassanowsky and Oliver C. Speck write, 'only another totalizing concept' that the filmmakers with whom it has been associated would necessarily dismiss. Yet in its persistence it has proved more nuanced and revealing of significant elements of contemporary cinema than it might first appear
Limitations of the questionnaire method:a reply to Hodroj, Latham, and Miller, ‘The moving open future, temporal phenomenology, and temporal passage’
No full textHodroj, Latham, and Miller’s target article is the latest in a slew of recent studies that seek to investigate temporal experience using a method that involves participants reading vignettes then completing questionnaires. I have significant misgivings about this method, and in this commentary, I discuss its limitations. I start by discussing the kinds of proposals that can, and cannot, be tested in principle using the questionnaire method, suggesting that some prominent proposals fall outside its scope. I illustrate this through an analogy with the opponent process theory of colour experience, where I suggest that the tools of cognitive neuroscience are needed. I then draw attention to some of the pitfalls of the questionnaire method in general, and to some problems specific to the current study. One major issue concerns the question of whether it has been shown that participants really understood their task. I give reasons for doubting this. First, I show that it is too easy to answer the comprehension questions correctly without understanding. Second, I argue that it is not credible that participants actually held the world view entailed by the combination of responses given by a significant minority of them, suggesting that there was significant confusion. I raise several other objections before concluding with a modest suggestion for future work
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