Russian-German five-year-olds: What omissions in sentence repetition tell us about linguistic knowledge, memory skills and their interrelation.

In error analyses using sentence repetition data, most authors focus on word types of omissions. The current study considers serial order in omission patterns independent of functional categories. Data was collected from Russian and German sentence repetition tasks performed by 53 five-year-old bilingual children. Number and positions of word omissions were analyzed. Serial order effects were found in both languages: medial errors made up the largest percentage of errors. Then, the position of omissions was compared to visuo-verbal n-back working memory and non-verbal visual forward short-term memory scores using stepwise hierarchical linear regression models, taking into account demographic variables and receptive language. The interaction differed between languages: there was a significant negative association between omissions in the medial position in German and the final position in Russian and the visuo-verbal n-back memory score. Our study contributes to the understanding of how working memory and language are intertwined in sentence repetition.

uPAR enhances malignant potential of triple-negative breast cancer by directly interacting with uPA and IGF1R.

BACKGROUND: Due to lack of a targeted therapy for the triple-negative breast cancer (TNBC) patients, it is important to explore this aggressive breast cancer type in more detail and to establish novel therapeutic approaches. TNBC is defined negative for the protein expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). One prominent feature of this cancer type is the frequent overexpression of major components of the urokinase-type plasminogen activator system (uPAS) including uPA, its receptor uPAR and the inhibitor PAI-1, which may be valuable as therapeutic targets. METHODS: Direct interactions of uPAR with interactors were demonstrated by immunoprecipitations and proximity ligation assays. For stable knockdowns of target proteins, lentiviral vectors were used and the effects were analysed by immunoblottings and using in vitro cell viability, migration and invasion assays. Immunohistochemical and statistical analyses of biomarkers and clinical parameters were conducted in a TNBC cohort (n = 174). RESULTS: Direct tumour-promoting interactions of uPAR with uPA and the insulin-like growth factor receptor 1 (IGF1R) were shown in TNBC cells and these interactions were significantly reduced (p = 0.001) when uPAR was downregulated. The combined knockdown of uPAR and uPA or IGF1R additively and significantly reduced cell viability, migration and invasion of the model cell lines. In TNBC tissue, the complexes formed by uPAR with uPA or with IGF1R significantly correlated with the histological grade (p = 0.0019) as well as with cathepsin B and D (p ≤ 0.0001) that are implicated in cell invasion and metastasis. CONCLUSIONS: Our outcomes show that not only overexpressed biomarkers promote tumourigenesis, but rather their interactions further potentiate tumour progression. This study emphasises the potential of combined approaches targeting uPAR and its interactors with regard to an improved therapy of TNBC.

Additive impact of HER2-/PTK6-RNAi on interactions with HER3 or IGF-1R leads to reduced breast cancer progression in vivo.

The human epidermal growth factor receptor 2 (HER2) and the protein tyrosine kinase 6 (PTK6) are often co- and over-expressed in invasive breast cancers. At early diagnosis, only distinct groups, such as HER2-or hormone receptor-positive benefit from a targeted therapy. However, a part of these tumours develops resistance within a year of administration of the drug but the majority of the patients depends on general therapies with severe side effects. A PTK6-directed approach does not yet exist. In our present study, we successfully demonstrate, in vitro and in vivo, a significantly additive reduction of tumourigenesis of breast cancer cells simultaneously depleted of both HER2 and PTK6. In comparison with single RNAi approaches, the combined RNAi (co-RNAi) led to a stronger reduced phosphorylation of tumour-promoting proteins. Moreover, the co-RNAi additively decreased cell migration as well as two and three dimensional cell proliferation in vitro. The in vivo experiments showed an additive reduction (p < 0.00001) in the growth of xenografts due to the co-RNAi compared with HER2 or PTK6 RNAi alone. Interestingly, the complexes of HER2 or PTK6 with tumour-relevant interaction partners, such as HER3 or the insulin-like growth factor receptor 1 (IGF-1R), respectively, were also reduced in xenografts although their protein expression levels were not affected following the co-RNAi of HER2 and PTK6. Our present study reveals the potential of using combined HER2- and PTK6- knockdown as a powerful strategy for the treatment of breast cancers. Therefore, the combined inhibition of these proteins may represent an attractive tool for efficient therapy of breast cancers.

Comparison of bone marrow aspiration at the sternum and the tuber coxae in middle-aged horses.

The objective of this study was to compare bone marrow (BM) aspirates from the sternum and the tuber coxae of middle-aged horses. Bone marrow was obtained from the sternum and both tubera coxae of 12 healthy, 13-year-old geldings. Two different puncture techniques were used for the tuber coxae. The 2 syringes used for sternal sampling were evaluated separately. The mononuclear cell (MNC) fraction of the BM was isolated and the mesenchymal stem cells (MSCs) were culture-expanded. At the sternum, BM aspiration was always possible. Bone marrow aspiration at the tuber coxae required straight and deep needle penetration combined with high negative pressure. With this technique a median sample amount of 11.0 mL with large individual variation was obtained. A median of 3.06 × 10(6) MNC/mL BM (1st syringe) and 2.46 × 10(6) MNC/mL BM (2nd syringe) was isolated from sternal samples. In contrast, the tuber coxae yielded a median of 0.27 × 10(6) MNC/mL BM. The first passage yielded a median of 2.19 × 10(6) MSC (1st syringe) and 1.13 × 10(6) MSC (2nd syringe) from sternal samples, compared to a significantly lower median number of MSC from tuber coxae BM (0.06 × 10(6) MSC). The number of MNC and MSC obtainable from the BM aspirates taken from the tuber coxae is significantly lower than that obtained from the sternal BM aspirates. Autologous BM for the equine athlete is particularly clinically relevant at an advanced age. Based on our findings, the tuber coxae cannot be recommended for BM aspiration in middle-aged horses.