Emerging role of contact-mediated cell communication in tissue development and diseases

This is the final version. Available on open access from Springer via the DOI in this recordCells of multicellular organisms are in continuous conversation with the neighbouring cells. The sender cells signal the receiver cells to influence their behaviour in transport, metabolism, motility, division, and growth. How cells communicate with each other can be categorized by biochemical signalling processes, which can be characterised by the distance between the sender cell and the receiver cell. Existing classifications describe autocrine signals as those where the sender cell is identical to the receiver cell. Complementary to this scenario, paracrine signalling describes signalling between a sender cell and a different receiver cell. Finally, juxtacrine signalling describes the exchange of information between adjacent cells by direct cell contact, whereas endocrine signalling describes the exchange of information, e.g., by hormones between distant cells or even organs through the bloodstream. In the last two decades, however, an unexpected communication mechanism has been identified which uses cell protrusions to exchange chemical signals by direct contact over long distances. These signalling protrusions can deliver signals in both ways, from sender to receiver and vice versa. We are starting to understand the morphology and function of these signalling protrusions in many tissues and this accumulation of findings forces us to revise our view of contact-dependent cell communication. In this review, we will focus on the two main categories of signalling protrusions, cytonemes and tunnelling nanotubes. These signalling protrusions emerge as essential structural components of a vibrant communication network in the development and tissue homeostasis of any multicellular organism.BM and SS are funded by a LSI start-up grant awarded to SS

Subtle changes in the flavour and texture of a drink enhance expectations of satiety

Background: The consumption of liquid calories has been implicated in the development of obesity and weight gain. Energy-containing drinks are often reported to have a weak satiety value: one explanation for this is that because of their fluid texture they are not expected to have much nutritional value. It is important to consider what features of these drinks can be manipulated to enhance their expected satiety value. Two studies investigated the perception of subtle changes in a drink’s viscosity, and the extent to which thick texture and creamy flavour contribute to the generation of satiety expectations. Participants in the first study rated the sensory characteristics of 16 fruit yogurt drinks of increasing viscosity. In study two, a new set of participants evaluated eight versions of the fruit yogurt drink, which varied in thick texture, creamy flavour and energy content, for sensory and hedonic characteristics and satiety expectations. Results: In study one, participants were able to perceive small changes in drink viscosity that were strongly related to the actual viscosity of the drinks. In study two, the thick versions of the drink were expected to be more filling and have a greater expected satiety value, independent of the drink’s actual energy content. A creamy flavour enhanced the extent to which the drink was expected to be filling, but did not affect its expected satiety. Conclusions: These results indicate that subtle manipulations of texture and creamy flavour can increase expectations that a fruit yogurt drink will be filling and suppress hunger, irrespective of the drink’s energy content. A thicker texture enhanced expectations of satiety to a greater extent than a creamier flavour, and may be one way to improve the anticipated satiating value of energy-containing beverages

Economic vulnerability and poor service delivery made it more difficult for shack-dwellers to comply with COVID-19 restrictions.

In South Africa, demand for housing close to viable/sustained sources of employment has far outstripped supply; and the size of the population living in temporary structures/shacks (and in poorly serviced informal settlements) has continued to increase. While such dwellings and settlements pose a number of established risks to the health of their residents, the present study aimed to explore whether they might also undermine the potential impact of regulations intended to safeguard public health, such as the stringent lockdown restrictions imposed to curb the spread of COVID-19 in 2020 and 2021. Using a representative sample of 1381 South African households surveyed in May–June 2021, the present study found that respondents in temporary structures/shacks were more likely to report non-compliance (or difficulty in complying) with lockdown restrictions when compared to those living in traditional/formal houses/flats/rooms/hostels (OR: 1.61; 95% CI: 1.06, 2.45). However, this finding was substantially attenuated and lost precision following adjustment for preceding socio-demographic and economic determinants of housing quality (adjusted OR: 1.20; 95% CI: 0.78, 1.87). Instead, respondents were far more likely to report non-compliance (or difficulty in complying) with COVID-19 lockdown restrictions if their dwellings lacked private/indoor toilet facilities (adjusted OR: 1.56; 95% CI: 1.08, 2.22) or if they were ‘Black/African’, young, poorly educated and under-employed (regardless of their socio-economic position, or whether they resided in temporary structures/shacks, respectively). Restrictions imposed to safeguard public health need to be more sensitively designed to accommodate the critical roles that poverty and inadequate service delivery play in limiting the ability of residents living in temporary structures/shacks and inadequately serviced dwellings/settlements to comply.Significance:• South Africans living in temporary structures/shacks are more likely to be poorly educated and underemployed, with fewer assets and limited access to basic household services.• Poverty and inadequate service delivery were more important determinants of compliance with COVID-19 restrictions than housing quality.• In the absence of improvements in economic circumstances and the delivery of basic household services, restrictions imposed to safeguard public health need to be more sensitively designed to take account of the structural barriers to compliance experienced by households where poverty and/or inadequate service delivery limit their ability to stay at home; maintain hygiene; and/or practise social distancing

Secreted Frizzled-related Protein 2 (sFRP2) Redirects Non-canonical Wnt Signaling from Fz7 to Ror2 during Vertebrate Gastrulation

This is the final version of the article. Available from American Society for Biochemistry and Molecular Biology via the DOI in this record.Convergent extension movements during vertebrate gastrulation require a balanced activity of non-canonical Wnt signaling pathways, but the factors regulating this interplay on the molecular level are poorly characterized. Here we show that sFRP2, a member of the secreted frizzled-related protein (sFRP) family, is required for morphogenesis and papc expression during Xenopus gastrulation. We further provide evidence that sFRP2 redirects non-canonical Wnt signaling from Frizzled 7 (Fz7) to the receptor tyrosine kinase-like orphan receptor 2 (Ror2). During this process, sFRP2 promotes Ror2 signal transduction by stabilizing Wnt5a-Ror2 complexes at the membrane, whereas it inhibits Fz7 signaling, probably by blocking Fz7 receptor endocytosis. The cysteine-rich domain of sFRP2 is sufficient for Ror2 activation, and related sFRPs can substitute for this function. Notably, direct interaction of the two receptors via their cysteine-rich domains also promotes Ror2-mediated papc expression but inhibits Fz7 signaling. We propose that sFRPs can act as a molecular switch, channeling the signal input for different non-canonical Wnt pathways during vertebrate gastrulation

Concerning the Phases of Annual Variations of Nuclear Decay Rates

Recent analyses of datasets acquired at the Brookhaven National Laboratory and at the Physikalisch-Technische Bundesanstalt both show evidence of pronounced annual variations, suggestive of a solar influence. However, the phases of decay-rate maxima do not correspond precisely to the phase of minimum Sun-Earth distance, as might then be expected. We here examine the hypothesis that decay rates are influenced by an unknown solar radiation, but that the intensity of the radiation is influenced not only by the variation in Sun-Earth distance, but also by a possible North-South asymmetry in the solar emission mechanism. We find that this can lead to phases of decay-rate maxima in the range 0 to 0.183 or 0.683 to 1 (September 6 to March 8) but that, according to this hypothesis, phases in the range 0.183 to 0.683 (March 8 to September 6) are "forbidden." We find that phases of the three datasets here analyzed fall in the allowed range.Comment: 5 Pages, 5 Figure

Appetitive and Dietary Effects of Consuming an Energy-Dense Food (Peanuts) with or Between Meals by Snackers and Non-Snackers.

Energy-dense foods are inconsistently implicated in elevated energy intake (EI). This may stem from other food properties and/or differences in dietary incorporation, that is, as snacks or with meals.Objective. Assess intake pattern and food properties on acute appetitive ratings (AR) and EI. Design. 201 normal and overweight adults consuming a standard lunch. Test loads of 1255.2 kJ (300 kcal) were added to the lunch or provided as snack. Loads (peanuts, snack mix, and snack mix with peanuts) were energy, macronutrient, and volumetrically matched with a lunch portion as control. Participants completed meal and snack sessions of their randomly assigned load. Results. No differences were observed in daily EI or AR for meal versus snack or treatment versus control. Consumption of peanuts as a snack tended to strengthen dietary compensation compared to peanuts or other loads with a meal. Conclusions. Inclusion of an energy-dense food as a snack or meal component had comparable influence on AR and EI. Peanuts tended to elicit stronger dietary compensation when consumed as a snack versus with a meal. If substantiated, this latter observation suggests that properties other than those controlled here (energy, macronutrient content, and volume) modify AR and EI

Pcdh18a regulates endocytosis of E-cadherin during axial mesoderm development in zebrafish

The notochord defines the axial structure of all vertebrates during development. Notogenesis is a result of major cell reorganization in the mesoderm, the convergence and the extension of the axial cells. However, it is currently not fully understood how these processes act together in a coordinated way during notochord formation. The prechordal plate is an actively migrating cell population in the central mesoderm anterior to the trailing notochordal plate cells. We show that prechordal plate cells express Protocadherin 18a (Pcdh18a), a member of the cadherin superfamily. We find that Pcdh18a-mediated recycling of E-cadherin adhesion complexes transforms prechordal plate cells into a cohesive and fast migrating cell group. In turn, the prechordal plate cells subsequently instruct the trailing mesoderm. We simulated cell migration during early mesoderm formation using a lattice-based mathematical framework and predicted that the requirement for an anterior, local motile cell cluster could guide the intercalation and extension of the posterior, axial cells. Indeed, a grafting experiment validated the prediction and local Pcdh18a expression induced an ectopic prechordal plate-like cell group migrating towards the animal pole. Our findings indicate that the Pcdh18a is important for prechordal plate formation, which influences the trailing mesodermal cell sheet by orchestrating the morphogenesis of the notochord