Accumulation of Multipotent Hematopoietic Progenitors in Peripheral Lymphoid Organs of Mice Over-expressing Interleukin-7 and Flt3-Ligand

Interleukin-7 (IL-7) and Flt3-ligand (FL) are two cytokines important for the generation of B cells, as manifested by the impaired B cell development in mice deficient for either cytokine or their respective receptors and by the complete block in B cell differentiation in the absence of both cytokines. IL-7 is an important survival and proliferation factor for B cell progenitors, whereas FL acts on several early developmental stages, prior to B cell commitment. We have generated mice constitutively over-expressing both IL-7 and FL. These double transgenic mice develop splenomegaly and lymphadenopathy characterized by tremendously enlarged lymph nodes even in young animals. Lymphoid, myeloid and dendritic cell numbers are increased compared to mice over-expressing either of the two cytokines alone and the effect on their expansion is synergistic, rather than additive. B cell progenitors, early progenitors with myeloid and lymphoid potential (EPLM), common lymphoid progenitors (CLP) and lineage−, Sca1+, kit+ (LSK) cells are all increased not only in the bone marrow but also in peripheral blood, spleen and even lymph nodes. When transplanted into irradiated wild-type mice, lymph node cells show long-term multilineage reconstitution, further confirming the presence of functional hematopoietic progenitors therein. Our double transgenic mouse model shows that sustained and combined over-expression of IL-7 and FL leads to a massive expansion of most bone marrow hematopoietic progenitors and to their associated presence in peripheral lymphoid organs where they reside and potentially differentiate further, thus leading to the synergistic increase in mature lymphoid and myeloid cell numbers. The present study provides further in vivo evidence for the concerted action of IL-7 and FL on lymphopoiesis and suggests that extramedullary niches, including those in lymph nodes, can support the survival and maintenance of hematopoietic progenitors that under physiological conditions develop exclusively in the bone marrow

A review of ecological gradient research in the Tropics: identifying research gaps, future directions, and conservation priorities

The Tropics are global centers of biodiversity. Ecological and land use gradients play a major role in the origin and maintenance of this diversity, yet a comprehensive synthesis of the corresponding large body of literature is still missing. We searched all ISI-listed journals for tropical gradient studies. From the resulting 1023 studies, we extracted study-specific information, and analyzed it using descriptive analytical tools and GLMs. Our results reveal that dry tropical areas are vastly understudied compared to their humid counterparts. The same holds true for large parts of Africa, but also the Philippines and the South Asian region. However, we also found that (applied) research output of developing tropical countries is nowadays on par with the output of developed countries. Vegetation and elevation were the most studied response variable and gradient, respectively. By contrast, inconspicous organisms such as oribatid mites and edaphic gradients were largely missing in the literature. Regarding biodiversity, tropical gradient studies dealt extensively with species richness and ecosystem diversity, but much less with genetic diversity. We encourage a wider use of modern statistical learning tools such as non-linear (spatio-temporal) regression and classification techniques, and simulations. Finally, we would embrace an even further development of synergies between applied and basic research and between researchers based in developed and in tropical countries. Keywords Synthesis Tropical ecology Environmental gradient relationships Biodiversit

Differential response of mouse thymic epithelial cell types to ionizing radiation-induced dna damage

Thymic epithelial cells (TECs) are the main components of the thymic stroma that support and control T-cell development. Preparative regimens using DNA-damaging agents, such as total body irradiation and/or chemotherapeutic drugs, that are necessary prior to bone marrow transplantation (BMT) have profound deleterious effects on the hematopoietic system, including the thymic stroma, which may be one of the main causes for the prolonged periods of T-cell deficiency and the inefficient T cell reconstitution that are common following BMT. The DNA damage response (DDR) is a complex signaling network that allows cells to respond to all sorts of genotoxic insults. Hypoxia is known to modulate the DDR and play a role affecting the survival capacity of different cell types. In this study, we have characterized in detail the DDR of cortical and medullary TEC lines and their response to ionizing radiation, as well as the effects of hypoxia on their DDR. Although both mTECs and cTECs display relatively high radio-resistance, mTEC cells have an increased survival capacity to ionizing radiation (IR)-induced DNA damage, and hypoxia specifically decreases the radio-resistance of mTECs by upregulating the expression of the pro-apoptotic factor Bim. Analysis of the expression of TEC functional factors by primary mouse TECs showed a marked decrease of highly important genes for TEC function and confirmed cTECs as the most affected cell type by IR. These findings have important implications for improving the outcomes of BMT and promoting successful T cell reconstitution

Soil texture and altitude, respectively, largely determine the floristic gradient of the most diverse fog oasis in the Peruvian desert

Studying species turnover along gradients is a key topic in tropical ecology. Crucial drivers, among others, are fog deposition and soil properties. In northern Peru, a fog-dependent vegetation formation develops on mountains along the hyper-arid coast. Despite their uniqueness, these fog oases are largely uninvestigated. This study addresses the influence of environmental factors on the vegetation of these unique fog oases. Accordingly, vegetation and soil properties were recorded on 66 4 × 4-m plots along an altitudinal gradient ranging from 200 to 950 m asl. Ordination and modelling techniques were used to study altitudinal vegetation belts and floristic composition. Four vegetation belts were identified: a low-elevation Tillandsia belt, a herbaceous belt, a bromeliad belt showing highest species richness and an uppermost succulent belt. Different altitudinal levels might reflect water availability, which is highest below the temperature inversion at around 700 m asl. Altitude alone explained 96% of the floristic composition. Soil texture and salinity accounted for 88%. This is in contrast with more humid tropical ecosystems where soil nutrients appear to be more important. Concluding, this study advances the understanding of tropical gradients in fog-dependent and ENSO-affected ecosystems

Comprehension of Arguments in Scientific Texts: Reliability and Validity of the Argument Structure Test (AST)

Muenchow H, Richter T, von der Muehlen S, Schmid S, Bruns KE, Berthold K. Verstehen von Argumenten in wissenschaftlichen Texten Reliabilität und Validität des Argumentstrukturtests (AST). Diagnostica. 2020;66(2):136-145.Zusammenfassung. Informelle Argumente sind in wissenschaftlichen Texten allgegenwärtig. Um solche Argumente verstehen und bewerten zu können, müssen Studierende ihre Struktur entschlüsseln. Zur Erfassung dieser Kompetenz wurde der computergestützte Argumentstrukturtest (AST) für Studierende sozial- und erziehungswissenschaftlicher Fächer sowie Lehramtsstudierende entwickelt. Die Testpersonen lesen kurze Texte mit informellen Argumenten und identifizieren ihre funktionalen Komponenten (z. B. Behauptung, Begründung, Schlussregel). Anhand einer Stichprobe von 225 Studierenden wurde der AST einer ersten Überprüfung seiner Reliabilität und Validität unterzogen. Dabei erwies sich der AST als intern valide, mit einer breiten Streuung der Itemschwierigkeiten. In einem explanatorischen Item-Response-Modell konnten die Itemschwierigkeiten sehr präzise durch theoretisch relevante Itemmerkmale, die das Argumentverstehen beeinflussen, vorhergesagt werden. Korrelationen mit verbaler Intelligenz und Schul- und Studienleistungen sprechen darüber hinaus für die Kriteriumsvalidität des Instruments.Informal arguments are omnipresent in scientific texts. In order to understand and evaluate such arguments, students have to decode their structure. To measure this competency, the computer-assisted argument structure test (AST) was developed for students of social and educational sciences as well as student teachers. The test-takers read short texts containing informal arguments and identify their functional components (e.g., claim, reason, warrant). On the basis of a sample of 225 students, the reliability and validity of the AST was examined for the first time. The AST proved to be reliable, with a wide range of item difficulties. In an explanatory item response model, the item difficulties were predicted very precisely through theoretically relevant item features that are known to influence argument comprehension. Correlations with verbal intelligence as well as school and study performance provided evidence for the criterion validity of the instrument

Permissive roles of cytokines interleukin-7 and Flt3 ligand in mouse B-cell lineage commitment

Hematopoietic cells are continuously generated throughout life from hematopoietic stem cells, thus making hematopoiesis a favorable system to study developmental cell lineage commitment. The main factors incorporating environmental signals to developing hematopoietic cells are cytokines, which regulate commitment of hematopoietic progenitors to the different blood lineages by acting either in an instructive or a permissive manner. Fms-like tyrosine kinase-3 (Flt3) ligand (FL) and Interleukin-7 (IL-7) are cytokines pivotal for B-cell development, as manifested by the severely compromised B-cell development in their absence. However, their precise role in regulating B-cell commitment has been the subject of debate. In the present study we assessed the rescue of B-cell commitment in mice lacking IL-7 but simultaneously overexpressing FL. Results obtained demonstrate that FL overexpression in IL-7-deficient mice rescues B-cell commitment, resulting in significant Ebf1 and Pax5 expression in Ly6D(+)CD135(+)CD127(+)CD19(-) precursors and subsequent generation of normal numbers of CD19(+) B-cell progenitors, therefore indicating that IL-7 can be dispensable for commitment to the B-cell lineage. Further analysis of Ly6D(+)CD135(+)CD127(+)CD19(-) progenitors in IL-7- or FL-deficient mice overexpressing Bcl2, as well as in IL-7 transgenic mice suggests that both FL and IL-7 regulate B-cell commitment in a permissive manner: FL by inducing proliferation of Ly6D(+)CD135(+)CD127(+)CD19(-) progenitors and IL-7 by providing survival signals to these progenitors

Permissive roles of cytokines interleukin-7 and flt3 ligand in mouse b-cell lineage commitment

Hematopoietic cells are continuously generated throughout life from hematopoietic stem cells, thus making hematopoiesis a favorable system to study developmental cell lineage commitment. The main factors incorporating environmental signals to developing hematopoietic cells are cytokines, which regulate commitment of hematopoietic progenitors to the different blood lineages by acting either in an instructive or a permissive manner. Fms-like tyrosine kinase-3 (Flt3) ligand (FL) and Interleukin-7 (IL-7) are cytokines pivotal for B-cell development, as manifested by the severely compromised B-cell development in their absence. However, their precise role in regulating B-cell commitment has been the subject of debate. In the present study we assessed the rescue of B-cell commitment in mice lacking IL-7 but simultaneously overexpressing FL. Results obtained demonstrate that FL overexpression in IL-7-deficient mice rescues B-cell commitment, resulting in significant Ebf1 and Pax5 expression in Ly6D(+) CD135(+)CD127(+)CD19(-) precursors and subsequent generation of normal numbers of CD19(+) B-cell progenitors, therefore indicating that IL-7 can be dispensable for commitment to the B-cell lineage. Further analysis of Ly6D(+)CD135(+)CD127(+)CD19(-) progenitors in IL-7-or FL-deficient mice overexpressing Bcl2, as well as in IL-7 transgenic mice suggests that both FL and IL-7 regulate B-cell commitment in a permissive manner: FL by inducing proliferation of Ly6D(+)CD135(+)CD127(+)CD19(-) progenitors and IL-7 by providing survival signals to these progenitors