The authors discovered that tendon cells respond to mechanical stimuli via integrins. Integrin β1 and integrin-linked kinase transmit mechanical stimuli from the membrane of tendon cells to activate mTOR/AKT signalling pathway. This pathway is critical for mRNA translation and synthesis of collagen, a fundamental component of tendon structure. Their model shows the importance of mTOR/AKT signalling on tendon development and adaptation to exercise and mechanical loading.
Read More
The bacterial stringent stress response, mediated by the signaling molecule guanosine tetraphosphate, ppGpp, has recently gained attention as being important during normal cellular growth and as a potential new therapeutic target, which warrants detailed mechanistic understanding. Here, we used intracellular protein tracking in Pseudomonas aeruginosa PAO1, which indicated that RelA was bound to the ribosome, while SpoT localized at the cell poles.…
Read More
This work, describing siRNA targeting FXIII-B (siFXIIIB), is the first pharmacologic approach for long-acting, reversible, and targeted decrease of FXIII-A activity in vivo. It enables the study of FXIII in a wide range of disease models, including in animals not amenable to genetic FXIII knockout. FXIII is considered a therapeutic target for preventing thrombosis, and siFXIIIB overcomes limitations of current antithrombics and thrombolytics by specifically enhancing endogenous fibrinolysis.
Read More
In some Huntington disease (HD) patients, the “loss of interruption” (LOI) variant eliminates an interrupting codon in the HTT CAG-repeat tract, which causes earlier age of onset (AOO). The magnitude of this effect is uncertain, since previous studies included few LOI carriers, and the variant also causes CAG size misestimation. We developed a rapid LOI detection screen, enabling unbiased frequency estimation among…
Read More
Endometrial carcinoma, the most common gynaecological cancer, develops from endometrial epithelium which is composed of secretory and ciliated cells. Pathologic classification is unreliable and there is a need for prognostic tools. We used single cell sequencing to study organoid model systems derived from normal endometrial endometrium to discover novel markers specific for endometrial ciliated or secretory cells. A marker of…
Read More
The somatic missense point mutation c.402C>G (p.C134W) in the FOXL2 transcription factor is pathognomonic for adult-type granulosa cell tumors (AGCT) and a diagnostic marker for this tumor type. However, the molecular consequences of this mutation and its contribution to the mechanisms of AGCT pathogenesis remain unclear. To explore these mechanisms, we engineered V5-FOXL2WT- and V5-FOXL2C134W-inducible isogenic cell lines and performed…
Read More
The authors show that integrins play a key role during fly hematopoiesis in regulating cell signals that control the behaviour of hematopoietic progenitors. Integrins regulate fly hematopoiesis directly, via integrin-mediated FAK signalling, and indirectly, by modulating ECM density. ECM density controls blood progenitor behaviour by influencing multiple signalling pathways, including bone morphogenetic protein and Hedgehog.
Read More

LIN28B Promotes the Development of Neuroendocrine Prostate Cancer

Compelling evidence has shown that LIN28b plays an important role in regulating the lineage switch of prostatic luminal epithelial cells to neuroendocrine cells. This study identifies LIN28B as a potential therapeutic target to treat therapy-induced neuroendocrine prostate cancer, a lethal subtype of therapy-resistant prostate cancers. This information will direct future strategies to design new therapeutics to treat this type of tumour.
Read More
This study not only uncovers mechanisms of diffuse large B cell lymphoma (DLBCL) treatment resistance, but also provides insight into the importance of genetic testing for DLBCL patients and demonstrates how this could be accomplished using minimally invasive analysis of circulating tumour DNA from blood samples. Screening for mutations in key resistance genes at the time of diagnosis and throughout treatment with R-CHOP may help clinicians better manage treatment strategies for DLBCL patients.
Read More
This work sheds new light on the molecular machinery that controls β-cell survival. The authors compared β-cells with four distinct genetic changes to determine the individual and combined contribution of two Bcl-2 family ‘executioner’ proteins, Bax and Bak, to β-cell death induced by the type of glucose and lipid-induced stress the β-cells experience in the development of type 2 diabetes.
Read More