Seven challenges in the multiscale modeling of multicellular tissues

The growth and dynamics of multicellular tissues involve tightly regulated and coordinated morphogenetic cell behaviors, such as shape changes, movement, and division, which are governed by subcellular machinery and involve coupling through short- and long-range signals. A key challenge in the fields of developmental biology, tissue engineering and regenerative medicine is to understand how relationships between scales produce emergent tissue-scale behaviors. Recent advances in molecular biology, live-imaging and ex vivo techniques have revolutionized our ability to study these processes experimentally. To fully leverage these techniques and obtain a more comprehensive understanding of the causal relationships underlying tissue dynamics, computational modeling approaches are increasingly spanning multiple spatial and temporal scales, and are coupling cell shape, growth, mechanics, and signaling. Yet such models remain challenging: modeling at each scale requires different areas of technical skills, while integration across scales necessitates the solution to novel mathematical and computational problems. This review aims to summarize recent progress in multiscale modeling of multicellular tissues and to highlight ongoing challenges associated with the construction, implementation, interrogation, and validation of such models. This article is categorized under: Reproductive System Diseases > Computational Models Metabolic Diseases > Computational Models Cancer > Computational Models

Digital preferences and perceptions of students in health professional courses at a leading Australian university: A baseline for improving digital skills and competencies in health graduates

This study aimed to improve understanding of graduate students’ digital preferences and perceptions to prepare them for work in the digitally enabled health sector. We surveyed 361 students from five disciplines to create a baseline of their digital capabilities. Results show that students were confident in engaging with day-to-day technologies required for discipline-specific learnings and most were reasonably aware of digital privacy and security. However, only 11% of the students reported having sufficient university support and services to develop their digital skills and competencies, and only 39% of the students believed they have the relevant skills for entering the workforce. To improve their understanding in this area, students attended a digital skills and employability workshop that was developed in partnership with teaching specialists, learning and teaching librarians and career services coordinators. Post-workshop findings show that this learning intervention positively impacted students’ understanding of their own digital capabilities and increased their awareness of the importance of this core skill for both the university and the workforce. Teaching staff can use these findings to improve student digital learning in health professional curricula, which will contribute to knowledge transfer and communication with digital health employers

Evaluation of dried blood spots for hepatitis B and D serology and nucleic acid testing

Areas with the highest burden of hepatitis B virus (HBV) infection are often low-middle-income countries with limited access to diagnosis due to isolation, affordability, and/or feasibility. Dried blood spots (DBSs) provide an alternative for remote areas where collection and transportation of serum is impractical. In this study, the application of DBS for serological and molecular detection of HBV and hepatitis D virus (HDV) was evaluated. Hepatitis B surface antigen was detected in 87 of 91 (95.6%) DBS. Seventeen of 21 (81%) had detectable HBeAg and 52 of 71 (73.2%) were anti-HBe positive. Anti-HD was detectable in 11 of 12 (91.6%) spiked control DBS after an initial failure to detect in patient DBS. HBV DNA was detected from 50 of 70 (71.4%) DBS with serum loads greater than 200 IU/mL in an in-house assay and 18 of 24 (75%) DBS with loads exceeding 389 IU/mL in a commercial assay. Using linear regression, HBV DNA loads from DBS were able to predict serum loads in 46 of 50 (92%) samples to within 1 log of actual serum load. HDV RNA was detected in 42 of 47 (89%) DBS with serum levels greater than 7200 IU/mL. DBSs are recommended for diagnosis of HBV, monitoring, and detection of high loads in pregnant women where peripheral blood testing remains unfeasible. Detection of HDV RNA from DBS may prove useful in endemic areas

On the trail of a missing Italian Masterpiece

Evidence that the painting by Paolo Veronese of The Pool of Bethesda, found its way to Scotland, when it was donated by Captain James Volum to his home town of Peterhea

Children’s Economic and Social Rights

Is there such a concept? Do they really exist? To speak of children’s economic and social rights implies an affirmative answer to these questions. But the drafting history of the Convention on the Rights of the Child reveals the fragile nature of the distinction between economic and social rights and civil and political rights for children. Indeed, if not for a late intervention from UNICEF, this distinction may well have been erased from the lexicon of children’s rights. It did however survive but only just. This chapter explores the vulnerable and often clouded relationship between children and economic and social rights. It labours to offer some doctrinal clarity with respect to the nature of this relationship which has been somewhat overlooked within the scholarship on economic and social rights - just what economic and social rights do children actually enjoy? - and what are the attendant obligations on States – are they any different to the obligations owed with respect to generic economic and social rights? But it does not shy away from the constructed and artificial nature of the distinction between the two sets of rights – an artificiality that has only become more acute as the meaning of all rights has expanded and muddied traditional points of distinction. Nor does it shy away from the serious challenges facing the effective implementation of all children’s rights – whether they are classified as economic and social rights or civil and political rights. Particular attention is also drawn to the need to bridge what is termed the disciplinary divide and shift the conception of children from a welfare based approach, which highlights their deficits and vulnerability to a rights-based approach, which recognises their strengths and evolving capacities

Effect of processing on bioaccessibility and bioavailability - of bioactive compounds in coffee beans

Coffee is one of the most prevalent and functional beverages around world owing to its rich content of bioactive compounds. Phenolic compounds and alkaloids are two primary groups of bioactive compounds in coffee beans, which have been proven healthy benefits in regular and suitable daily consumption. They have been recognized as protective factors, especially phenolic compounds, to perform high antioxidant capacities and potential to relieve the occurrence of chronic diseases and partial cancer. The content and composition of bioactive and anti-nutritional compounds in coffee beans can be mainly influenced by variety, processing and storage conditions. The cultivar of Arabica coffee beans (C. arabica) exhibits lower content of phenolic compounds but similar anti-nutritional substances with the comparison to Robusta (C. canephora). Comparing to green coffee beans, reasonable roasting contributes to the improvement of phenolic content and its total antioxidant activity because of the liberation of bound phenolic compounds and the generation of novel compounds with antioxidant activity. Over intensive roasting will not only decrease the number of bioactive compounds within the coffee beans but also stimulate the generation of endogenous anti-nutritional compounds, which consequently reduce the coffee nutritional value. The fluctuations of moisture content during storage would be the primary reason of the changes in the content of bioactive compounds. Phenolic compounds in coffee beans perform outstanding bioaccessibility but relatively lower absorption efficiency because of the combination with other molecules. Suitable roasting would improve the bioavailability of bioactive compounds. The interaction between phenolic compounds and proteins would also influence the bioavailability and bioactivity of bioactive compounds and final nutritional value after consumption

Scoring the refrain: Young African men in a diasporic context

This chapter tells the story of what could be called a project failure. The project was a 12-week venture with newly immigrant young African men living in Melbourne, Australia. It was designed to assist the young men with building social connections through participating in experimental music workshops and performing music in the live experimental music scene. A successful project would have seen at least some of these young men progress into employment in the music industry. This did not happen. The chapter presents an analysis of the project through the lens of music performance and the act of ‘scoring’ bodies with life ‘refrains’. Although this is a reflection on how the Refrain makes visible the affective register in the collective transformation of bodies through music, this chapter is also a challenge to treat music as more than just a metaphor in service of ‘youth connectivity’. This is a challenge to take seriously the concrete ontology of the youth-music-collective as young bodies become-other, with and through music

Macromolecular Engineering of Thermoresponsive Metal-Phenolic Networks

Dynamic nanostructured materials that can react to physical and chemical stimuli have attracted interest in the biomedical and materials science fields. Metal-phenolic networks (MPNs) represent a modular class of such materials: these networks form via coordination of phenolic molecules with metal ions and can be used for surface and particle engineering. To broaden the range of accessible MPN properties, we report the fabrication of thermoresponsive MPN capsules using FeIII ions and the thermoresponsive phenolic building block biscatechol-functionalized poly(N-isopropylacrylamide) (biscatechol-PNIPAM). The MPN capsules exhibited reversible changes in capsule size and shell thickness in response to temperature changes. The temperature-induced capsule size changes were influenced by the chain length of biscatechol-PNIPAM and catechol-to-FeIII ion molar ratio. The metal ion type also influenced the capsule size changes, allowing tuning of the MPN capsule mechanical properties. AlIII-based capsules, having a lower stiffness value (10.7 mN m-1), showed a larger temperature-induced size contraction (∼63%) than TbIII-based capsules, which exhibit a higher stiffness value (52.6 mN m-1) and minimal size reduction (<1%). The permeability of the MPN capsules was controlled by changing the temperature (25-50 °C)─a reduced permeability was obtained as the temperature was increased above the lower critical solution temperature of biscatechol-PNIPAM. This temperature-dependent permeability behavior was exploited to encapsulate and release model cargo (500 kDa fluorescein isothiocyanate-tagged dextran) from the capsules; approximately 70% was released over 90 min at 25 °C. This approach provides a synthetic strategy for developing dynamic and thermoresponsive-tunable MPN systems for potential applications in biological science and biotechnology

Oligonucleotide correction of an intronic TIMMDC1 variant in cells of patients with severe neurodegenerative disorder

TIMMDC1 encodes the Translocase of Inner Mitochondrial Membrane Domain-Containing protein 1 (TIMMDC1) subunit of complex I of the electron transport chain responsible for ATP production. We studied a consanguineous family with two affected children, now deceased, who presented with failure to thrive in the early postnatal period, poor feeding, hypotonia, peripheral neuropathy and drug-resistant epilepsy. Genome sequencing data revealed a known, deep intronic pathogenic variant TIMMDC1 c.597-1340A>G, also present in gnomAD (~1/5000 frequency), that enhances aberrant splicing. Using RNA and protein analysis we show almost complete loss of TIMMDC1 protein and compromised mitochondrial complex I function. We have designed and applied two different splice-switching antisense oligonucleotides (SSO) to restore normal TIMMDC1 mRNA processing and protein levels in patients' cells. Quantitative proteomics and real-time metabolic analysis of mitochondrial function on patient fibroblasts treated with SSOs showed restoration of complex I subunit abundance and function. SSO-mediated therapy of this inevitably fatal TIMMDC1 neurologic disorder is an attractive possibility