Cells and gene expression programs in the adult human heart

Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and strategies to improve therapeutic opportunities require deeper understanding of the molecular processes of the normal heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavor. Here, using large-scale single cell and nuclei transcriptomic profiling together with state-of-the-art analytical techniques, we characterise the adult human heart cellular landscape covering six anatomical cardiac regions (left and right atria and ventricles, apex and interventricular septum). Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, revealing distinct subsets in the atria and ventricles indicative of diverse developmental origins and specialized properties. Further we define the complexity of the cardiac vascular network which includes clusters of arterial, capillary, venous, lymphatic endothelial cells and an atrial-enriched population. By comparing cardiac cells to skeletal muscle and kidney, we identify cardiac tissue resident macrophage subsets with transcriptional signatures indicative of both inflammatory and reparative phenotypes. Further, inference of cell-cell interactions highlight a macrophage-fibroblast-cardiomyocyte network that differs between atria and ventricles, and compared to skeletal muscle. We expect this reference human cardiac cell atlas to advance mechanistic studies of heart homeostasis and disease

Modeling the Measurements of Cochlear Microcirculation and Hearing Function after Loud Noise

Objective: Recent findings support the crucial role of microcirculatory disturbance and ischemia for hearing impairment especially after noise-induced hearing loss (NIHL). The aim of this study was to establish an animal model for in vivo analysis of cochlear microcirculation and hearing function after a loud noise to allow precise measurements of both parameters in vivo. Study Design: Randomized controlled trial. Setting: Animal study. Subjects and Methods: After assessment of normacusis (0 minutes) using evoked auditory brainstem responses (ABRs), noise (106-dB sound pressure level [SPL]) was applied to both ears in 6 guinea pigs for 30 minutes while unexposed animals served as controls. In vivo fluorescence microscopy of the stria vascularis capillaries was performed after surgical exposure of 1 cochlea. ABR measurements were derived from the contralateral ear. Results: After noise exposure, red blood cell velocity was reduced significantly by 24.3% (120 minutes) and further decreased to 44.5% at the end of the observation (210 minutes) in contrast to stable control measurements. Vessel diameters were not affected in both groups. A gradual decrease of segmental blood flow became significant (38.1%) after 150 minutes compared with controls. Hearing thresholds shifted significantly from 20.0 ± 5.5 dB SPL (0 minutes) to 32.5 ± 4.2dB SPL (60 minutes) only in animals exposed to loud noise. Conclusion: With regard to novel treatments targeting the stria vascularis in NIHL, this standardized model allows us to analyze in detail cochlear microcirculation and hearing function in vivo

Correlation between centrality metrics and their application to the opinion model

In recent decades, a number of centrality metrics describing network properties of nodes have been proposed to rank the importance of nodes. In order to understand the correlations between centrality metrics and to approximate a high-complexity centrality metric by a strongly correlated low-complexity metric, we first study the correlation between centrality metrics in terms of their Pearson correlation coefficient and their similarity in ranking of nodes. In addition to considering the widely used centrality metrics, we introduce a new centrality measure, the degree mass. The m order degree mass of a node is the sum of the weighted degree of the node and its neighbors no further than m hops away. We find that the B_{n}, the closeness, and the components of x_{1} are strongly correlated with the degree, the 1st-order degree mass and the 2nd-order degree mass, respectively, in both network models and real-world networks. We then theoretically prove that the Pearson correlation coefficient between x_{1} and the 2nd-order degree mass is larger than that between x_{1} and a lower order degree mass. Finally, we investigate the effect of the inflexible antagonists selected based on different centrality metrics in helping one opinion to compete with another in the inflexible antagonists opinion model. Interestingly, we find that selecting the inflexible antagonists based on the leverage, the B_{n}, or the degree is more effective in opinion-competition than using other centrality metrics in all types of networks. This observation is supported by our previous observations, i.e., that there is a strong linear correlation between the degree and the B_{n}, as well as a high centrality similarity between the leverage and the degree.Comment: 20 page

The ‘integrative approach’ and labour regulation and Indonesia: prospects and challenges

In contrast to theories of regulation which bypass the state and cede regulatory authority to private regimes, the scholar Kevin Kolben makes a cogent argument for the state to be brought back to centre stage in labour regulation, but envisages that private actors can develop and strengthen its capacity. This article considers the utility of what he terms an integrative approach for Indonesia. In line with what the approach advocates, the article examines the relationships between private actors and the state and considers the extent to which the former can communicate, interact with and incentivise the latter in ways which strengthen its regulatory capacity. Several challenges are identified. Finally, the potential of the Better Work Programme in Indonesia to further the goals of the approach is assessed

What young people report about the personal characteristics needed for social science research after carrying out their own investigations in an after-school club

Several arguments have been put forward about the benefits of young people carrying out their own social science research in terms of empowering their voices and their participation. Much less attention has been paid to investigating the understandings young people develop about the research process itself. Seven twelve-year-olds carried out self-directed social science research into a topic of their choice. Towards the end of their six months experience we used a questionnaire and follow-up semi-structured interviews to investigate, from a socio-cultural perspective, what the young people thought about being a researcher. Thematic analysis of the interviews identified three themes and eight subthemes suggesting that they were aware of: the need to demonstrate researcher/research integrity (be thorough, truthful, orderly, and have a good understanding of research process); the need for good interpersonal skills and standards; and good self-management skills (be resilient, agentic, committed, and good at time management). We discuss how first-hand social science research experience might: be relevant to several areas of schooling; give young people experience of the personal characteristics important for success; help young people to realise that they can be social science researchers, and offer advanced and novel learning experiences outside the constraints of the school curriculum

Gay male academics in UK business and management schools: negotiating heteronormativities in everyday work life

This paper contributes to a neglected topic area about lesbian, gay, bisexual and trans people’s employment experiences in UK business and management schools. Drawing on queer theory to problematize essentialist notions of sexuality, we explore how gay male academics negotiate and challenge discourses of heteronormativity within different work contexts. Using in-depth interview data, the paper shows that gay male academics are continually constrained by heteronormativity in constructing viable subject positions as ‘normal’, often having to reproduce heteronormative values that squeeze opportunities for generating non-heteronormative ‘queer’ sexualities, identities and selves. Constructing a presence as an openly gay academic can invoke another binary through which identities are (re)constructed: as either ‘gay’ (a cleaned up version of gay male sexuality that sustains a heteronormative moral order) or ‘queer’ (cast as radical, disruptive and sexually promiscuous). Data also reveal how gay men challenge organizational heteronormativities through teaching and research activities, producing reverse discourses and creating alternative knowledge/power regimes, despite institutional barriers and risks of perpetuating heteronormative binaries and constructs. Study findings call for pedagogical and research practices that ‘queer’ (rupture, destabilize, disrupt) management knowledge and the heterosexual/homosexual binary, enabling non-heteronormative voices, perspectives, identities and ways of relating to emerge in queer(er) business and management schools

A measure of individual role in collective dynamics

Identifying key players in collective dynamics remains a challenge in several research fields, from the efficient dissemination of ideas to drug target discovery in biomedical problems. The difficulty lies at several levels: how to single out the role of individual elements in such intermingled systems, or which is the best way to quantify their importance. Centrality measures describe a node's importance by its position in a network. The key issue obviated is that the contribution of a node to the collective behavior is not uniquely determined by the structure of the system but it is a result of the interplay between dynamics and network structure. We show that dynamical influence measures explicitly how strongly a node's dynamical state affects collective behavior. For critical spreading, dynamical influence targets nodes according to their spreading capabilities. For diffusive processes it quantifies how efficiently real systems may be controlled by manipulating a single node.Comment: accepted for publication in Scientific Report