IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1

Macrophages (M Phi s) colonize tissues during inflammation in two distinct ways: recruitment of monocyte precursors and proliferation of resident cells. We recently revealed a major role for IL-4 in the proliferative expansion of resident M Phi s during a Th2-biased tissue nematode infection. We now show that proliferation of M Phi s during intestinal as well as tissue nematode infection is restricted to sites of IL-4 production and requires M Phi-intrinsic IL-4R signaling. However, both IL-4R alpha-dependent and -independent mechanisms contributed to M Phi proliferation during nematode infections. IL-4R-independent proliferation was controlled by a rise in local CSF-1 levels, but IL-4R alpha expression conferred a competitive advantage with higher and more sustained proliferation and increased accumulation of IL-4R alpha(+) compared with IL-4R alpha(-) cells. Mechanistically, this occurred by conversion of IL-4R alpha(+) M Phi s from a CSF-1-dependent to -independent program of proliferation. Thus, IL-4 increases the relative density of tissue M Phi s by overcoming the constraints mediated by the availability of CSF-1. Finally, although both elevated CSF1R and IL-4R alpha signaling triggered proliferation above homeostatic levels, only CSF-1 led to the recruitment of monocytes and neutrophils. Thus, the IL-4 pathway of proliferation may have developed as an alternative to CSF-1 to increase resident M Phi numbers without coincident monocyte recruitment

Transforming scholarship in the archives through handwritten text recognition:Transkribus as a case study

Purpose: An overview of the current use of handwritten text recognition (HTR) on archival manuscript material, as provided by the EU H2020 funded Transkribus platform. It explains HTR, demonstrates Transkribus, gives examples of use cases, highlights the affect HTR may have on scholarship, and evidences this turning point of the advanced use of digitised heritage content. The paper aims to discuss these issues. - Design/methodology/approach: This paper adopts a case study approach, using the development and delivery of the one openly available HTR platform for manuscript material. - Findings: Transkribus has demonstrated that HTR is now a useable technology that can be employed in conjunction with mass digitisation to generate accurate transcripts of archival material. Use cases are demonstrated, and a cooperative model is suggested as a way to ensure sustainability and scaling of the platform. However, funding and resourcing issues are identified. - Research limitations/implications: The paper presents results from projects: further user studies could be undertaken involving interviews, surveys, etc. - Practical implications: Only HTR provided via Transkribus is covered: however, this is the only publicly available platform for HTR on individual collections of historical documents at time of writing and it represents the current state-of-the-art in this field. - Social implications: The increased access to information contained within historical texts has the potential to be transformational for both institutions and individuals. - Originality/value: This is the first published overview of how HTR is used by a wide archival studies community, reporting and showcasing current application of handwriting technology in the cultural heritage sector

Pan-African Genetic Structure in the African Buffalo (Syncerus caffer): Investigating Intraspecific Divergence

The African buffalo (Syncerus caffer) exhibits extreme morphological variability, which has led to controversies about the validity and taxonomic status of the various recognized subspecies. The present study aims to clarify these by inferring the pan-African spatial distribution of genetic diversity, using a comprehensive set of mitochondrial D-loop sequences from across the entire range of the species. All analyses converged on the existence of two distinct lineages, corresponding to a group encompassing West and Central African populations and a group encompassing East and Southern African populations. The former is currently assigned to two to three subspecies (S. c. nanus, S. c. brachyceros, S. c. aequinoctialis) and the latter to a separate subspecies (S. c. caffer). Forty-two per cent of the total amount of genetic diversity is explained by the between-lineage component, with one to seventeen female migrants per generation inferred as consistent with the isolation-with-migration model. The two lineages diverged between 145 000 to 449 000 years ago, with strong indications for a population expansion in both lineages, as revealed by coalescent-based analyses, summary statistics and a star-like topology of the haplotype network for the S. c. caffer lineage. A Bayesian analysis identified the most probable historical migration routes, with the Cape buffalo undertaking successive colonization events from Eastern toward Southern Africa. Furthermore, our analyses indicate that, in the West-Central African lineage, the forest ecophenotype may be a derived form of the savanna ecophenotype and not vice versa, as has previously been proposed. The African buffalo most likely expanded and diverged in the late to middle Pleistocene from an ancestral population located around the current-day Central African Republic, adapting morphologically to colonize new habitats, hence developing the variety of ecophenotypes observed today