Cell migration is crucial for both physiological and pathological processes. Current in vitro cell motility assays suffer from various drawbacks, including insufficient temporal and/or optical ...resolution, or the failure to include a controlled chemotactic stimulus. Here, we address these limitations with a migration chamber that utilizes a self-sustaining chemotactic gradient to induce locomotion through confined environments that emulate physiological settings. Dynamic real-time analysis of both population-scale and single-cell movement are achieved at high resolution. Interior surfaces can be functionalized through adsorption of extracellular matrix components, and pharmacological agents can be administered to cells directly, or indirectly through the chemotactic reservoir. Direct comparison of multiple cell types can be achieved in a single enclosed system to compare inherent migratory potentials. Our novel microfluidic design is therefore a powerful tool for the study of cellular chemotaxis, and is suitable for a wide range of biological and biomedical applications.
In this paper the results of a first attempt to ignite an inverted fireball with a magnetron sputter source are presented. The conducted measurements show that there is no inverted fireball visible ...to the naked eye present during the experiments. However, some features are observed that indicate at least an initial onset of such an inverted fireball with an interruption before it is fully developed. In the course of the experiments magnetron sputtered molybdenum films have been deposited inside a highly transparent gridded anode and the obtained films have been analysed. It turns out that even without a visible inverted fireball being present, the film morphology and mechanical properties such as elastic modulus, hardness and surface roughness have changed significantly compared to a setup without inverted fireball anode. Additionally, the deposition rate is elevated by up to 20% inside the inverted fireball anode compared to the reference setup, although with a nearly threefold increase in total input power (cathode power + grid anode power). This increase in deposition rate was achieved despite the fact that a mesh electrode with only about 37% transparency was used. On the other hand, it was demonstrated that the use of additional gridded electrodes in such a device triggers instabilities and non-linearities in the plasma, which might be of interest for further fundamental research.
•First attempt to ignite an inverted fireball in a magnetron sputter chamber•Indication of initial onset of an inverted fireball (IFB)•Enhancement of mechanical properties of Mo films by using IFB grid
The cytoskeletal organization of detached and circulating tumor cells (CTCs) is currently not well defined and may provide potential targets for new therapies to limit metastatic tumor spread. In ...vivo, CTCs reattach in distant tissues by a mechanism that is tubulin-dependent and suppressed by polymerized actin. The cytoskeletal mechanisms that promote reattachment of CTCs match exactly with the mechanisms supporting tubulin microtentacles (McTN), which we have recently identified in detached breast tumor cells. In this study, we aimed to investigate how McTN formation is affected by the microtubule-associated protein, tau, which is expressed in a subset of chemotherapy-resistant breast cancers. We demonstrate that endogenous tau protein localizes to McTNs and is both necessary and sufficient to promote McTN extension in detached breast tumor cells. Tau-induced McTNs increase reattachment of suspended cells and retention of CTCs in lung capillaries. Analysis of patient-matched primary and metastatic tumors reveals that 52% possess tau expression in metastases and 26% display significantly increased tau expression over disease progression. Tau enrichment in metastatic tumors and the ability of tau to promote tumor cell reattachment through McTN formation support a model in which tau-induced microtubule stabilization provides a selective advantage during tumor metastasis.
River regulation and water extraction has significantly altered flow regimes and reduced flood events in many inland river systems. Environmental flows have been adopted in many systems to mitigate ...the ecological impacts of river regulation, however a lack of knowledge regarding the interrelationship between flow regimes, carbon transport and instream productivity make prioritising water management difficult. To address this knowledge gap, we conducted a study on the Namoi River in the Murray-Darling Basin, Australia, monitoring changes in dissolved organic carbon (DOC), nutrient dynamics and planktonic food web structure during a period of variable flows. Nutrient and DOC concentrations were positively correlated with river discharge and zooplankton concentrations were highest post flow events. Planktonic chlorophyll-
a
, increased DOC concentration and higher discharge were the most influential drivers of change in zooplankton communities. Further, our results indicated that flow events increased production through both heterotrophic and autotrophic pathways, significantly boosting zooplankton concentration compared to base flow conditions across all measured flow events. We suggest even small in-channel flow events can be important for increasing basal and zooplankton production in rivers, and therefore should be protected or promoted by environmental flow management, particularly during drought conditions.
Lichens are symbioses of two organisms, a fungal mycobiont and a photoautotrophic photobiont. In nature, many lichens tolerate extreme environmental conditions and thus became valuable models in ...astrobiological research to fathom biological resistance towards non-terrestrial conditions; including space exposure, hypervelocity impact simulations as well as space and Martian parameter simulations. All studies demonstrated the high resistance towards non-terrestrial abiotic factors of selected extremotolerant lichens. Besides other adaptations, this study focuses on the morphological and anatomical traits by comparing five lichen species—
Circinaria gyrosa
,
Rhizocarpon geographicum
,
Xanthoria elegans
,
Buellia frigida
,
Pleopsidium chlorophanum
—used in present-day astrobiological research. Detailed investigation of thallus organization by microscopy methods allows to study the effect of morphology on lichen resistance and forms a basis for interpreting data of recent and future experiments. All investigated lichens reveal a common heteromerous thallus structure but diverging sets of morphological-anatomical traits, as intra-/extra-thalline mucilage matrices, cortices, algal arrangements, and hyphal strands. In
B. frigida, R. geographicum
, and
X. elegans
the combination of pigmented cortex, algal arrangement, and mucilage seems to enhance resistance, while subcortex and algal clustering seem to be crucial in
C. gyrosa
, as well as pigmented cortices and basal thallus protrusions in
P. chlorophanum
. Thus, generalizations on morphologically conferred resistance have to be avoided. Such differences might reflect the diverging evolutionary histories and are advantageous by adapting lichens to prevalent abiotic stressors. The peculiar lichen morphology demonstrates its remarkable stake in resisting extreme terrestrial conditions and may explain the high resistance of lichens found in astrobiological research.
Abstract Computerized cognitive training (CCT) interventions are increasing in their use in outpatient mental health settings. These interventions have demonstrated efficacy for improving functional ...outcomes when combined with rehabilitation interventions. It has recently been suggested that patients with more cognitive impairment have a greater therapeutic response and that reduced engagement in training can identify cases who manifest low levels of benefit from treatment. Participants were psychiatric rehabilitation clients, with diagnoses of major depression, bipolar disorder and schizophrenia. Newly admitted cases received CCT, delivered via Brain HQ, with cognitive functioning divided into groups on the basis of a BACS t-score of 40 or less vs. more. Training engagement was indexed by the number of training levels achieved per day trained. Forty-nine cases trained on average for 17 days and completed a mean of 150 levels. Overall, patients improved by an average of 4.4 points (0.44 SD) in BACS t-scores ( p < .001). Improvements were positively correlated with training engagement ( r = 0.30, p < .05), but not with days trained ( r = 0.09) or levels earned ( r = 0.03) alone. Patients with higher levels of baseline cognitive performance had reduced cognitive gains ( p < .003), but did not have less training engagement ( p = .97). Diagnoses did not predict cognitive gains ( p = .93) or target engagement ( p = .74). Poorer performance at baseline and higher levels of training engagement accounted for >10% in independent variance in cognitive gains. The mean level of cognitive improvement far exceeded practice effects. The index of engagement, levels achieved per training day, is easily extracted from the training records of patients, which would allow for early and continuous monitoring of treatment engagement in CCT activities and therapist intervention as needed to improve engagement.
Selectins promote metastasis by mediating specific interactions between selectin ligands on tumor cells and selectin‐expressing host cells in the microvasculature. Using affinity chromatography in ...conjunction with tandem mass spectrometry and bioinformatics tools, we identified mucin 16 (MUC16) as a novel selectin ligand expressed by metastatic pancreatic cancer cells. While up‐regulated in many pancreatic cancers, the biological function of sialofucosylated MUC16 has yet to be fully elucidated. To address this, we employed blot rolling and cell‐free flow‐based adhesion assays using MUC16 immunopurified from pancreatic cancer cells and found that it efficiently binds E‐ and L‐ but not P‐selectin. The selectin‐binding determinants are sialofucosylated structures displayed on O‐and N‐linked glycans. Silencing MUC16 expression by RNAi markedly reduces pancreatic cancer cell binding to E‐ and L‐selectin under flow. These findings provide a novel integrated perspective on the enhanced metastatic potential associated with MUC16 overexpression and the role of selectins in metastasis.—Chen, S.‐H., Dallas, M. R., Balzer, E. M., Konstantopoulos, K. Mucin 16 is a functional selectin ligand on pancreatic cancer cells. FASEB J. 26, 1349‐1359 (2012). www.fasebj.org
Introduction. This study analyzed the patient outcomes following endovascular aortic aneurysm repair (EVAR) for infrarenal aortic pathologies with very narrow aortic bifurcations using the AFX stent ...graft. Methods. The data was retrieved from the archived medical records of 35 patients treated for abdominal aortic aneurysm (AAA) (48.6%) or penetrating aortic ulcer (PAU) (51.4%) with very narrow aortic bifurcation between January 2013 and May 2020. Patient survival, freedom from endoleak (EL), and limb occlusion were estimated applying the Kaplan–Meier method. Results. The mean follow-up time was 20.4±22.8 months. The mean aortic bifurcation diameter was 15.8±2.2 mm. Technical success was 100%, and no procedure-related deaths occurred. Two type II ELs occurred within 30-day follow-up. We observed one common iliac artery stenosis at four months and one type III EL at 54 months in the same patient, both of which required re-intervention. Overall patient survival was 95±5% (AAA: 100%; PAU: 89±10%), freedom from limb occlusion was 94±5% (AAA: 91±9%; PAU: 100%), freedom from type II EL was 94±4% (AAA: 88±8%; PAU: 100%), and freedom from EL type III was 83±15% (AAA: 80±18%; PAU: 100%) at the end of the follow-up period. Conclusions. Very narrow aortic bifurcations may predispose patients to procedure-related complications following EVAR. Our results suggest a safe use of the AFX stent graft in such scenarios. The overall short- and long-term procedure-related patient outcomes are satisfying albeit they may seem superior for PAU when compared to AAA.
This study considers anisotropic microstructures with typical dimensions of a few 10 µm which have been created on steel surfaces by laser surface texturing (LST). It is shown that the subsequent ...deposition of thin molybdenum nitride coatings by high-power impulse magnetron sputtering (HiPIMS) leads to surfaces that conserve the surface microstructures and exhibit a remarkably large resistance against mechanical wear. Tribological experiments with steel counter bodies are substantially influenced by the relative orientation of the structures and the wear track. Both friction and wear are shown to be modified by more than 30%, with the main effect being the removal of abrasion particles from the mechanical contact. Experiments with alumina counter bodies that hardly provide wear particles show that the orientation has no effect on the abrasion of the counter body. The novelty of the article lies in the combination of MoN coatings with surface texturing.
During metastasis, invading cells produce various actin-based membrane protrusions that promote directional migration and proteolysis of extracellular matrix (ECM). Observations of actin staining ...within thin, tubulin-based microtentacle (McTN) protrusions in suspended MDA-MB-231 tumor cells, prompted an investigation of whether McTNs are structural or functional analogs of invadopodia. We show here that MDA-MB-231 cells are capable of producing invadopodia and McTNs, both of which contain F-actin. Invadopodium formation was enhanced by the expression of a constitutively active c-Src kinase, and repressed by the expression of dominant-negative, catalytically inactive form of c-Src. In contrast, expression of inactive c-Src significantly increased McTN formation. Direct inhibition of c-Src with the SU6656 inhibitor compound also significantly enhanced McTN formation, but suppressed invadopodia, including the appearance of F-actin cores and phospho-cortactin foci, as well as completely blocking focal degradation of ECM. In addition, silencing of Tks5 in Src-transformed fibroblasts blocked invadopodia without affecting McTNs. Genetic modification of c-Src activity that promoted McTN formation augmented capillary retention of circulating tumor cells in vivo and rapid re-attachment of suspended cells in vitro, even though invadopodia were strongly suppressed. These results indicate that McTNs are capable of enhancing tumor cell reattachment, even in the absence of Tks5 and active Src, and define separate cytoskeletal mechanisms and functions for McTNs and invadopodia.
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