WASP integrates substrate topology and cell polarity to guide neutrophil migration

To control their shape and movement, cells leverage nucleation promoting factors (NPFs) to regulate when and where they polymerize actin. Here we investigate the role of the immune-specific NPF WASP during neutrophil migration. Endogenously-tagged WASP localizes to substrate-induced plasma membrane deformations. Super-resolution imaging of live cells reveals that WASP preferentially enriches to the necks of these substrate-induced membrane invaginations, a distribution that could support substrate pinching. Unlike other curvature-sensitive proteins, WASP only enriches to membrane deformations at the cell front, where it controls Arp2/3 complex recruitment and actin polymerization. Despite relatively normal migration on flat substrates, WASP depletion causes defects in topology sensing and directed migration on textured substrates. WASP therefore both responds to and reinforces cell polarity during migration. Surprisingly, front-biased WASP puncta continue to form in the absence of Cdc42. We propose that WASP integrates substrate topology with cell polarity for 3D guidance by selectively polymerizing actin around substrate-induced membrane deformations at the leading edge. A misregulation of WASP-mediated contact guidance could provide insight into the immune disorder Wiskott-Aldrich syndrome.

Is Vipera orlovi a Distinct Hybrid Species?

The species status of Vipera orlovi is discussed in the context of the concept of hybrid speciation. The genome of this Caucasian viper is composed of the genomes of Vipera kaznakovi (major part) and of Vipera renardi (about 20%). V. orlovi is intermediate in ecology between its ‘parental species,’ however its habitat is not the typical habitat of neither V. kaznakovi nor V. renardi. As all three taxa are allopatric, there is no evidence of current geneflow between them. Pleistocene climatic changes may have mediated contact and hybridization between V. kaznakovi and V. renardi. The resulting hybrid flock may have had a wider ecological range than its parental species, enabling a descendant lineage to occupy a novel niche which was previously unoccupied. Similar scenarios of hybrid speciation have probably occurred in vipers throughout the Caucasus. Although the future fate of this hybrid speciation remains open unless full genetic isolation has occurred, we propose to grant species status to Vipera orlovi. This is in line with the genotypic cluster species concept and the unified species concept.

Glypiated FGF directs contact-mediated bidirectional signaling to self-regulate tissue-specific dispersion

ABSTRACTDuring development, a handful of signals sculpt diverse tissue architectures. How the same signal produces different tissue/context-specific information and outcomes is poorly understood. We explored the basis that programs tissue-specific FGF dispersion and interpretation by cytoneme-mediated contact-dependent communication. Although aDrosophilaFGF was thought to be freely secreted, we discovered that it is glypiated and GPI-anchored on the source cell surface, which inhibits non-specific secretion but facilitates tissue-specific cytoneme contact formation and contact-dependent release. For long-distance signaling, source and recipient cells extend FGF-containing and FGFR-containing cytonemes that contact and recognize each other by CAM-like receptor-ligand binding. FGF-FGFR binding reciprocally induces forward and reverse signaling in recipient and source cells, responses of which polarize their cytonemes toward each other to mutually self-sustain contacts. FGFR-bound FGF’s subsequent unanchoring hand-delivers FGF to receiving cytonemes and dissociates contacts. Thus, while cytonemes spatiotemporally control FGF dispersion/interpretation, FGF selfregulates its tissue-specific signaling by controlling cytonemes.

Simulating SARS-CoV-2 epidemics by region-specific variables and modeling contact tracing app containment

Targeted contact-tracing through mobile phone apps has been proposed as an instrument to help contain the spread of COVID-19 and manage the lifting of nation-wide lock-downs currently in place in USA and Europe. However, there is an ongoing debate on its potential efficacy, especially in light of region-specific demographics. We built an expanded SIR model of COVID-19 epidemics that accounts for region-specific population densities, and we used it to test the impact of a contact-tracing app in a number of scenarios. Using demographic and mobility data from Italy and Spain, we used the model to simulate scenarios that vary in baseline contact rates, population densities, and fraction of app users in the population. Our results show that, in support of efficient isolation of symptomatic cases, app-mediated contact-tracing can successfully mitigate the epidemic even with a relatively small fraction of users, and even suppress altogether with a larger fraction of users. However, when regional differences in population density are taken into consideration, the epidemic can be significantly harder to contain in higher density areas, highlighting potential limitations of this intervention in specific contexts. This work corroborates previous results in favor of app-mediated contact-tracing as mitigation measure for COVID-19, and draws attention on the importance of region-specific demographic and mobility factors to achieve maximum efficacy in containment policies.

Teachers Foster Intergroup Empathy

This study examined a professional development program aimed at supporting Jewish civics teachers in their efforts to promote empathy among their students toward Israeli Arabs. Previous results indicated an increase in outgroup empathy among teachers who watched and reflected upon clips from a television sitcom. This article focuses on skills teachers developed and strategies they designed and implemented following their experience with empathy processes. Our findings underscore the educative potential of indirect mediated contact in segregated societies, and the importance of developing empathic processes among teachers before they embark on the challenge of supporting their students in such endeavors.

What guidance does HIPAA offer to providers considering familial risk notification and cascade genetic testing?

Background It is unclear how the Health Insurance Portability and Accountability Act (HIPAA) should be interpreted in the context of sharing of genomic information between family members. Methods The authors analyzed the HIPAA Privacy Rule, reviewed the literature and constructed a clinical scenario to inform how HIPAA can be interpreted for multiple forms of patient- and provider-mediated genetic risk notification. Results Under HIPAA, healthcare providers can lawfully notify relatives to recommend genetic risk assessment using multiple approaches, including supporting the patient telling their own relatives, contacting relatives directly with the patient’s authorization, or contacting a relative’s provider directly. Conclusions Multiple forms of patient- or provider-mediated contact of relatives are already legally permissible under HIPAA, are consistent with ethical obligations of care to patients and their families, and could result in improved population health through identification of clinically actionable disease risk. Unanswered questions remain about implementation and impacts of provider-mediated programs.