TY  - JOUR
A1  - Herrmann, Andreas B.
A1  - Müller, Martha‐Lena
A1  - Orth, Martin F.
A1  - Müller, Jörg P.
A1  - Zernecke, Alma
A1  - Hochhaus, Andreas
A1  - Ernst, Thomas
A1  - Butt, Elke
A1  - Frietsch, Jochen J.
T1  - Knockout of LASP1 in CXCR4 expressing CML cells promotes cell persistence, proliferation and TKI resistance
JF  - Journal of Cellular and Molecular Medicine
N2  - Chronic myeloid leukaemia (CML) is a clonal myeloproliferative stem cell disorder characterized by the constitutively active BCR‐ABL tyrosine kinase. The LIM and SH3 domain protein 1 (LASP1) has recently been identified as a novel BCR‐ABL substrate and is associated with proliferation, migration, tumorigenesis and chemoresistance in several cancers. Furthermore, LASP1 was shown to bind to the chemokine receptor 4 (CXCR4), thought to be involved in mechanisms of relapse. In order to identify potential LASP1‐mediated pathways and related factors that may help to further eradicate minimal residual disease (MRD), the effect of LASP1 on processes involved in progression and maintenance of CML was investigated. The present data indicate that not only overexpression of CXCR4, but also knockout of LASP1 contributes to proliferation, reduced apoptosis and migration as well as increased adhesive potential of K562 CML cells. Furthermore, LASP1 depletion in K562 CML cells leads to decreased cytokine release and reduced NK cell‐mediated cytotoxicity towards CML cells. Taken together, these results indicate that in CML, reduced levels of LASP1 alone and in combination with high CXCR4 expression may contribute to TKI resistance.
KW  - BCR‐ABL
KW  - CML
KW  - CXCR4
KW  - LASP1
KW  - nilotinib
KW  - precursor cells
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214122
VL  - 24
IS  - 5
SP  - 2942
EP  - 2955
ER  - 
TY  - JOUR
A1  - Thorn, Simon
A1  - Chao, Anne
A1  - Georgiev, Konstadin B.
A1  - Müller, Jörg
A1  - Bässler, Claus
A1  - Campbell, John L.
A1  - Jorge, Castro
A1  - Chen, Yan-Han
A1  - Choi, Chang-Yong
A1  - Cobb, Tyler P.
A1  - Donato, Daniel C.
A1  - Durska, Ewa
A1  - Macdonald, Ellen
A1  - Feldhaar, Heike
A1  - Fontaine, Jospeh B.
A1  - Fornwalt, Paula J.
A1  - Hernández Hernández, Raquel María
A1  - Hutto, Richard L.
A1  - Koivula, Matti
A1  - Lee, Eun-Jae
A1  - Lindenmayer, David
A1  - Mikusinski, Grzegorz
A1  - Obrist, Martin K.
A1  - Perlík, Michal
A1  - Rost, Josep
A1  - Waldron, Kaysandra
A1  - Wermelinger, Beat
A1  - Weiß, Ingmar
A1  - Zmihorski, Michal
A1  - Leverkus, Alexandro B.
T1  - Estimating retention benchmarks for salvage logging to protect biodiversity
JF  - Nature Communications
N2  - Forests are increasingly affected by natural disturbances. Subsequent salvage logging, a widespread management practice conducted predominantly to recover economic capital, produces further disturbance and impacts biodiversity worldwide. Hence, naturally disturbed forests are among the most threatened habitats in the world, with consequences for their associated biodiversity. However, there are no evidence-based benchmarks for the proportion of area of naturally disturbed forests to be excluded from salvage logging to conserve biodiversity. We apply a mixed rarefaction/extrapolation approach to a global multi-taxa dataset from disturbed forests, including birds, plants, insects and fungi, to close this gap. We find that 757% (mean +/- SD) of a naturally disturbed area of a forest needs to be left unlogged to maintain 90% richness of its unique species, whereas retaining 50% of a naturally disturbed forest unlogged maintains 73 +/- 12% of its unique species richness. These values do not change with the time elapsed since disturbance but vary considerably among taxonomic groups. Salvage logging has become a common practice to gain economic returns from naturally disturbed forests, but it could have considerable negative effects on biodiversity. Here the authors use a recently developed statistical method to estimate that ca. 75% of the naturally disturbed forest should be left unlogged to maintain 90% of the species unique to the area.
KW  - natural disturbance
KW  - bird communities
KW  - forest
KW  - management
KW  - beetle
KW  - conservation
KW  - windthrow
KW  - diversity
KW  - impact
KW  - fire
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230512
VL  - 11
ER  -