The Role of TKS5 in Chromosome Stability and Bladder Cancer Progression

TKS5 promotes invasion and migration through the formation of invadopodia in some tumour cells, and it also has an important physiological function in cell migration through podosome formation in various nontumour cells. To date, the role of TKS5 in urothelial cells, and its potential role in BC initiation and progression, has not yet been addressed. Moreover, the contribution of TKS5 to ploidy control and chromosome stability has not been reported in previous studies. Therefore, in the present study, we wished to address the following questions: (i) Is TKS5 involved in the ploidy control of urothelial cells? (ii) What is the mechanism that leads to aneuploidy in response to TKS5 knockdown? (iii) Is TKS5 an oncogene or tumour-suppressor gene in the context of BC? (iv) Does TKS5 affect the proliferation, migration and invasion of BC cells? We assessed the gene and protein expressions via qPCR and Western blot analyses in a set of nontumour cell strains (Y235T, HBLAK and UROtsa) and a set of BC cell lines (RT4, T24, UMUC3 and J82). Following the shRNA knockdown in the TKS5-proficient cells and the ectopic TKS5 expression in the cell lines with low/absent TKS5 expression, we performed functional experiments, such as metaphase, invadopodia and gelatine degradation assays. Moreover, we determined the invasion and migration abilities of these genetically modified cells by using the Boyden chamber and wound-healing assays. The TKS5 expression was lower in the bladder cancer cell lines with higher invasive capacities (T24, UMUC3 and J82) compared to the nontumour cell lines from human ureter (Y235T, HBLAK and UROtsa) and the noninvasive BC cell line RT4. The reduced TKS5 expression in the Y235T cells resulted in augmented aneuploidy and impaired cell division. According to the Boyden chamber and wound-healing assays, TKS5 promotes the invasion and migration of bladder cancer cells. According to the present study, TKS5 regulates the migration and invasion processes of bladder cancer (BC) cell lines and plays an important role in genome stability.     

Time‐series and extended Karhunen–Loève analysis of turbulent drag reduction in polymer solutions

Direct numerical simulations and statistical analysis techniques are used to study the drag‐reducing effect of polymer additives on turbulent channel flow in minimal domains. Additionally, a new formulation of Karhunen–Loève decomposition for viscoelastic flows is introduced, allowing the dominant features of the polymer stress fields to be characterized. In minimal channels, there are intervals of “active” and “hibernating” turbulence that display very different structural and energetic characteristics; the present work illustrates how the statistics of these intervals evolve over the entire range of drag reduction (DR) levels. The effect of viscoelasticity on minimal channel turbulence is twofold: first, it strongly suppresses the active turbulent dynamics that predominate in Newtonian flow and second, at sufficiently high Weissenberg number it stabilizes the dynamics of hibernating turbulence, allowing it to predominate in the maximum drag reduction regime. In this regime, the stress fluctuations become delocalized from the wall region, encompassing the entire flow domain. © 2014 American Institute of Chemical Engineers AIChE J, 60: 1460–1475, 2014     

Teriflunomide Preserves Neuronal Activity and Protects Mitochondria in Brain Slices Exposed to Oxidative Stress

Teriflunomide (TFN) limits relapses in relapsing–remitting multiple sclerosis (RRMS) by reducing lymphocytic proliferation through the inhibition of the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) and the subsequent modulation of de novo pyrimidine synthesis. Alterations of mitochondrial function as a consequence of oxidative stress have been reported during neuroinflammation. Previously, we showed that TFN prevents alterations of mitochondrial motility caused by oxidative stress in peripheral axons. Here, we aimed to validate TFN effects on mitochondria and neuronal activity in hippocampal brain slices, in which cellular distribution and synaptic circuits are largely preserved. TFN effects on metabolism and neuronal activity were investigated by assessing oxygen partial pressure and local field potential in acute slices. Additionally, we imaged mitochondria in brain slices from the transgenic Thy1-CFP/COX8A)S2Lich/J (mitoCFP) mice using two-photon microscopy. Although TFN could not prevent oxidative stress-related depletion of ATP, it preserved oxygen consumption and neuronal activity in CNS tissue during oxidative stress. Furthermore, TFN prevented mitochondrial shortening and fragmentation of puncta-shaped and network mitochondria during oxidative stress. Regarding motility, TFN accentuated the decrease in mitochondrial displacement and increase in speed observed during oxidative stress. Importantly, these effects were not associated with neuronal viability and did not lead to axonal damage. In conclusion, during conditions of oxidative stress, TFN preserves the functionality of neurons and prevents morphological and motility alterations of mitochondria.     

Changes in the perceived duration of a narrowband sound induced by a preceding stimulus.

The authors show that a narrowband noise (NBN) is perceived as longer when presented immediately after a wideband noise (WBN), compared to when the WBN is absent. This effect depended on the WBN’s frequency spectrum overlapping that of the NBN, and it increased as the duration of the WBN increased up to 300 ms. It decreased when a silent gap was introduced between the WBN and NBN, but remained significant for an easily detectable gap of 40 ms. A correlate of the effect was observed in the mismatch negativity (MMN) to a deviant stimulus, consisting of a WBN + NBN, presented in a sequence of more common isolated WBNs. The MMN latency was longer for an on-frequency than for an off-frequency WBN; and, more importantly, the size of this difference correlated across participants with the difference in perceived duration. A rhythm-adjustment experiment showed that the presence of an on-frequency WBN immediately preceding a tone caused that tone to be heard as starting earlier than when the WBN was absent. The results are discussed in relation to the continuity illusion and models of duration encoding. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Schrifttumsberichte

Ohne Zusammenfassung     

Family health and mental health six years after economic stress and unemployment

This study is a follow-up of 39 working class couples who were interviewed after suffering economic stress or unemployment and again six years later. Repeated measures related to economics, stress, family functioning, anxiety, and depression were collected and analyzed for couples and for husbands and wives separately. A model of long-term coping was suggested for future testing. Initially stressed families appeared to grow stronger. Mental health correlated negatively to family problems. Depressed wives seemed to maintain their depression over time if they perceived family life as stressful. Irrespective of marital problems, husbands were less likely to stay depressed.     

A language independent error recovery method for LL(1) parsers

An efficient and systematic LL(1) error recovery method is presented that has been implemented for an LL(1) parser generator. Error messages which provide good diagnostic information are generated automatically. Error correction is done by discarding some input symbols and popping up some symbols from the parsing-stack in order to restore the parser to a valid configuration. Thus, symbol deletions and insertions are simulated. The choice between different possible corrections is made by comparing the cost of the inserted (popped) symbols with the reliability value of the recovery symbol (the first input symbol that is not discarded). Our concept of reliability is based on the observation that input symbols differ from each other in their ability to serve as recovery points. A high reliability value of a symbol asserts that it was probably not placed in the input by accident. So it is reasonable not to discard that symbol but to resume parsing. This is done even if a string with high insert-cost has to be inserted before that symbol in order to fit it to the part of the program that has already been analysed. The error recovery routine is invoked only when an error is detected. Thus, there is no additional time required for parsing correct programs. Error-correcting parsers for different languages, including Pascal, have been generated. Some experimental results are summarized.