Single-cell profiling and zebrafish avatars reveal LGALS1 as immunomodulating target in glioblastoma

Glioblastoma (GBM) remains the most malignant primary brain tumor, with a median survival rarely exceeding 2 years. Tumor heterogeneity and an immunosuppressive microenvironment are key factors contributing to the poor response rates of current therapeutic approaches. GBM-associated macrophages (GAMs) often exhibit immunosuppressive features that promote tumor progression. However, their dynamic interactions with GBM tumor cells remain poorly understood. Here, we used patient-derived GBM stem cell cultures and combined single-cell RNA sequencing of GAM-GBM co-cultures and real-time in vivo monitoring of GAM-GBM interactions in orthotopic zebrafish xenograft models to provide insight into the cellular, molecular, and spatial heterogeneity. Our analyses revealed substantial heterogeneity across GBM patients in GBM-induced GAM polarization and the ability to attract and activate GAMs—features that correlated with patient survival. Differential gene expression analysis, immunohistochemistry on original tumor samples, and knock-out experiments in zebrafish subsequently identified LGALS1 as a primary regulator of immunosuppression. Overall, our work highlights that GAM-GBM interactions can be studied in a clinically relevant way using co-cultures and avatar models, while offering new opportunities to identify promising immune-modulating targets

Silviculture of Scots pine in Belgium

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Scots pine in Belgium and the Netherlands

El Pino silvestre es la especie forestal más importante en los Países Bajos (39 % de la superficie forestal), y una de las tres principales coníferas en Bélgica (10 % de la superficie forestal). Los objetivos de la gestión para el Pino silvestre han cambiado mucho durante el siglo XX: desde la producción de apeas de minas hasta los años setenta, hasta la gestión multifuncional de los bosques al final del siglo. Se discuten los tipos naturales de bosques con Pino silvestre en los Países Bajos y Bélgica. En Bélgica el Pino silvestre no se considera indígena. Se describe la sucesión forestal con Pino silvestre, principalmente desde brezales degradados o arenas transportadas por el viento hasta los ecosistemas forestales. Normalmente, el Pino silvestre desempeña un papel importante en el comienzo de esta sucesión, pero decrece cuando las especies de frondosas se convierten en dominantes en el dosel arbóreo en la etapas sucesionales posteriores. La selvicultura ha cambiado mucho, a través de la sucesión forestal y por el cambio en los objetivos de gestión. Los iniciales monocultivos plantados se reemplazan con estructuras forestales más diversas a menudo utilizando la regeneración natural. Las cortas a hecho se realizan cada vez menos, llevando a cabo muchas intervenciones en una escala pequeña. La edad del rodal aumenta y el dosel cada vez se abre más a través de las claras, hasta que se elimina todo el dosel. La calidad del sitio también está cambiando, principalmente por la acidificación y los aportes de nitrógeno por la contaminación. Mientras que la superficie de Pino silvestre disminuye gradualmente, la biodiversidad originalmente baja en los rodales jóvenes está aumentando en las zonas que permanecen con Pino silvestre

Aspects of biodiversity of Scots pine forests in Europe

Management  of Scots pine, the most widely distributed conifer in the world, was often  based on    clearfelling and replanting regimes, resulting in a rather poor  biodiversity value. However, there    is nowadays a general expectation to increase biodiversity by applying a  more complex    silviculture.    Although present knowledge of genetic factors is insufficient to draw firm  conclusions on the    desirable level of genetic diversity, it seems unlikely that current  silvicultural practices will limit    genetic diversity in Scots pine    Native pinewoods are rare in Europe, but have a flora and fauna of high  conservation value.    Therefore they must be recognized as a priority habitat under the European  Commission's    Habitat Directive. The high conservation value of native stands is a  function of their old-growth    structure that provides a rare habitat.    A number of measures should be taken in all types of Scots pine forests to  enhance biodiversity.    Firstly, old growth habitats should be promoted. Foresters have to accept  that a small    percentage of the pine resource should be managed upon much longer  rotations. Secondly,    retention of deadwood should be encouraged. Dead and dying wood are key  components of    stand structure and act as key substrates for many associated species, such  as microbes,    invertebrates, small mammals and birds. Furthermore, a complex stand  structure should be    promoted at both the horizontal and the vertical scale. A small scale  forestry, group regeneration    systems, natural regeneration, introduction of broadleaves and stronger  thinnings are strongly    recommended. Availability of quite precise niches significantly increases  biodiversity value.    Conservation of isolated populations, found under extreme environmental  conditions, is an    absolute need. Populations endangered either by their small size or by  environmental stresses,    hybridization with other species or human interference should be primarily  conserved. Forest    edges support a range of taxa, and open habitats can comprise many  different plant community    types. A large number of organisms are directly or indirectly dependent on  or favoured by fire.    However, enhancing biodiversity provokes also some risks. Generally,  browsing is considered    as a moderate risk. Introduced species, such as aspen, act as an alternate  host to the rust.    Open species can present a threat to the European pine marten, dying and  deadwood can    provide breeding habitats for pest species (Tomicus  piniperda), burning increases the risk of    seedlings being attacked pine fire fungus (Rhizina  undulata) and forest edges may be an    attractive habitat for pest insects.    An extension of existing growth models is needed to incorporate  biodiversity issues in forest    management planning. Distance dependent individual tree growth models should  be developed.    Sets of indicators for biodiversity must integrate compositional,  structural and functional attributes. Attributes such as species richness,  species abundance, species diversity, horizontal and vertical distribution,  tree age, tree size, stand diversity, architectural complexity, genetic  variants and deadwood are needed for the establishment of biodiversity  indices. Assessment of functional phenomena needs the knowledge of the  driving biotic environmental factors.</jats:p

Role of delta-like-4/Notch in the formation and wiring of the lymphatic network in zebrafish.

OBJECTIVE: To study whether Notch signaling, which regulates cell fate decisions and vessel morphogenesis, controls lymphatic development. METHODS AND RESULTS: In zebrafish embryos, sprouts from the axial vein have lymphangiogenic potential because they give rise to the first lymphatics. Knockdown of delta-like-4 (Dll4) or its receptors Notch-1b or Notch-6 in zebrafish impaired lymphangiogenesis. Dll4/Notch silencing reduced the number of sprouts producing the string of parchordal lymphangioblasts; instead, sprouts connecting to the intersomitic vessels were formed. At a later phase, Notch silencing impaired navigation of lymphatic intersomitic vessels along their arterial templates. CONCLUSIONS: These studies imply critical roles for Notch signaling in the formation and wiring of the lymphatic network

El Pino silvestre en Bélgica y los Países Bajos

Scots pine is the most important tree species in the Netherlands (39 % of the forest area), and one of the three main conifer species in Belgium (10 % of the forest area). The management goals for Scots pine have changed very much during the twentieth century: from the production of mining timber until the 1970’s, to multifunctional forest management at the end of the century. The natural forest types with Scots pine in the Netherlands are discussed. In Belgium, Scots pine is not considered to be indigenous. The forest succession with Scots pine is described, mostly from degraded heathland or windblown sand to forest ecosystems. Usually, Scots pine plays an important role in the beginning of this succession, but decreases when broad-leaved tree species become dominant in the forest canopy in later successional stages. The silviculture has changed very much, both through forest succession and change in management goals. The early, planted monocultures are replaced with more diverse forest structures often using natural regeneration. Clearcutting is performed less and less; with many interventions taking place on a small scale. Stand age is increasing, and the canopy becomes progressively more open through ongoing thinnings until the complete canopy is removed. The site quality is also changing, mainly through acidification and nitrogen inputs from air pollution. While the area of Scots pine is gradually decreasing, the originally low biodiversity in the young stands is now increasing in the remaining areas with Scots pine.El Pino silvestre es la especie forestal m&aacute;s importante en los Pa&iacute;ses Bajos (39 % de la superficie forestal), y una de las tres principales con&iacute;feras en B&eacute;lgica (10 % de la superficie forestal). Los objetivos de la gesti&oacute;n para el Pino silvestre han cambiado mucho durante el siglo XX: desde la producci&oacute;n de apeas de minas hasta los a&ntilde;os setenta, hasta la gesti&oacute;n multifuncional de los bosques al final del siglo. Se discuten los tipos naturales de bosques con Pino silvestre en los Pa&iacute;ses Bajos y B&eacute;lgica. En B&eacute;lgica el Pino silvestre no se considera ind&iacute;gena. Se describe la sucesi&oacute;n forestal con Pino silvestre, principalmente desde brezales degradados o arenas transportadas por el viento hasta los ecosistemas forestales. Normalmente, el Pino silvestre desempe&ntilde;a un papel importante en el comienzo de esta sucesi&oacute;n, pero decrece cuando las especies de frondosas se convierten en dominantes en el dosel arb&oacute;reo en la etapas sucesionales posteriores. La selvicultura ha cambiado mucho, a trav&eacute;s de la sucesi&oacute;n forestal y por el cambio en los objetivos de gesti&oacute;n. Los iniciales monocultivos plantados se reemplazan con estructuras forestales m&aacute;s diversas a menudo utilizando la regeneraci&oacute;n natural. Las cortas a hecho se realizan cada vez menos, llevando a cabo muchas intervenciones en una escala peque&ntilde;a. La edad del rodal aumenta y el dosel cada vez se abre m&aacute;s a trav&eacute;s de las claras, hasta que se elimina todo el dosel. La calidad del sitio tambi&eacute;n est&aacute; cambiando, principalmente por la acidificaci&oacute;n y los aportes de nitr&oacute;geno por la contaminaci&oacute;n. Mientras que la superficie de Pino silvestre disminuye gradualmente, la biodiversidad originalmente baja en los rodales j&oacute;venes est&aacute; aumentando en las zonas que permanecen con Pino silvestre

Silvicultural interpretation of natural vegetation dynamics in ageing Scots pine stands for their conversion into mixed broadleaved stands

In many West-European regions there is principal consensus on the conversion of homogeneous even-aged Scots pine plantations into mixed broadleaved stands. In recent years, interest is growing for conversion management in which managers try to maximise the use of natural processes by steering or accelerating spontaneously occurring developments, or initiating new developments, according to current insight into natural vegetation dynamics and the factors controlling it. We present the most comprehensive models of natural vegetation dynamics in ageing temperate Scots pine forest ecosystems on poor sandy soils in Europe¿a linear succession model and a multiple pathway model. We use the multiple pathway model to define three silvicultural strategies for the conversion of ageing Scots pine stands, in accordance with natural processes. For each strategy the conversion target, the conversion type and recommendations on scale, intensity and frequency of management interventions are presented. The proposed strategies provide an uncomplicated ecological framework for planning and implementing conversion management within a realistic time span. Limitations of the proposed strategies and alternative management approaches are discussed. The described models and strategies are valid in large areas of the West-European Atlantic biogeographic region