Many properties of solids result from the fact that in a periodic crystal structure, electronic wave functions are delocalized over many lattice sites. Electrons should become increasingly localized ...when a strong electric field is applied. So far, this Wannier-Stark regime has been reached only in artificial superlattices. Here we show that extremely transient bias over the few-femtosecond period of phase-stable mid-infrared pulses may localize electrons even in a bulk semiconductor like GaAs. The complicated band structure of a three-dimensional crystal leads to a strong blurring of field-dependent steps in the Wannier-Stark ladder. Only the central step emerges strongly in interband electro-absorption because its energetic position is dictated by the electronic structure at an atomic level and therefore insensitive to the external bias. In this way, we demonstrate an extreme state of matter with potential applications due to e.g., its giant optical non-linearity or extremely high chemical reactivity.
Astrocytic brain tumours, including glioblastomas, are incurable neoplasms characterized by diffusely infiltrative growth. Here we show that many tumour cells in astrocytomas extend ultra-long ...membrane protrusions, and use these distinct tumour microtubes as routes for brain invasion, proliferation, and to interconnect over long distances. The resulting network allows multicellular communication through microtube-associated gap junctions. When damage to the network occurred, tumour microtubes were used for repair. Moreover, the microtube-connected astrocytoma cells, but not those remaining unconnected throughout tumour progression, were protected from cell death inflicted by radiotherapy. The neuronal growth-associated protein 43 was important for microtube formation and function, and drove microtube-dependent tumour cell invasion, proliferation, interconnection, and radioresistance. Oligodendroglial brain tumours were deficient in this mechanism. In summary, astrocytomas can develop functional multicellular network structures. Disconnection of astrocytoma cells by targeting their tumour microtubes emerges as a new principle to reduce the treatment resistance of this disease.
The extent to which early events shape tumor evolution is largely uncharacterized, even though a better understanding of these early events may help identify key vulnerabilities in advanced tumors. ...Here, using genetically defined mouse models of small cell lung cancer (SCLC), we uncovered distinct metastatic programs attributable to the cell type of origin. In one model, tumors gain metastatic ability through amplification of the transcription factor NFIB and a widespread increase in chromatin accessibility, whereas in the other model, tumors become metastatic in the absence of NFIB-driven chromatin alterations. Gene-expression and chromatin accessibility analyses identify distinct mechanisms as well as markers predictive of metastatic progression in both groups. Underlying the difference between the two programs was the cell type of origin of the tumors, with NFIB-independent metastases arising from mature neuroendocrine cells. Our findings underscore the importance of the identity of cell type of origin in influencing tumor evolution and metastatic mechanisms.
We show that SCLC can arise from different cell types of origin, which profoundly influences the eventual genetic and epigenetic changes that enable metastatic progression. Understanding intertumoral heterogeneity in SCLC, and across cancer types, may illuminate mechanisms of tumor progression and uncover how the cell type of origin affects tumor evolution.
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Crossing the blood-brain barrier is a crucial, rate-limiting step of brain metastasis. Understanding of the mechanisms of cancer cell extravasation from brain microcapillaries is limited as the ...underlying cellular and molecular processes cannot be adequately investigated using in vitro models and endpoint in vivo experiments. Using ultrastructural and functional imaging, we demonstrate that dynamic changes of activated brain microcapillaries promote the mandatory first steps of brain colonization. Successful extravasation of arrested cancer cells occurred when adjacent capillary endothelial cells (EC) entered into a distinct remodeling process. After extravasation, capillary loops were formed, which was characteristic of aggressive metastatic growth. Upon cancer cell arrest in brain microcapillaries, matrix-metalloprotease 9 (MMP9) was expressed. Inhibition of MMP2/9 and genetic perturbation of MMP9 in cancer cells, but not the host, reduced EC projections, extravasation, and brain metastasis outgrowth. These findings establish an active role of ECs in the process of cancer cell extravasation, facilitated by cross-talk between the two cell types. This extends our understanding of how host cells can contribute to brain metastasis formation and how to prevent it.
Tracking single extravasating cancer cells using multimodal correlative microscopy uncovers a brain seeding mechanism involving endothelial remodeling driven by cancer cell-derived MMP9, which might enable the development of approaches to prevent brain metastasis. See related commentary by McCarty, p. 1167.
Anthropogenic activities are increasing the atmospheric carbon dioxide (CO
2
); around a third of the CO
2
emitted by these activities has been taken up by the ocean. Nevertheless, this marine ...ecosystem service of regulation remains largely invisible to society, and not enough is known about regional differences and trends in sea-air CO
2
fluxes (FCO2), especially in the Southern Hemisphere. The objectives of this work were as follows: first to put values of FCO2 integrated over the exclusive economic zones (EEZ) of five Latin-American countries (Argentina, Brazil, Mexico, Peru, and Venezuela) into perspective regarding total country-level greenhouse gases (GHG) emissions. Second, to assess the variability of two main biological factors affecting FCO2 at marine ecological time series (METS) in these areas. FCO2 over the EEZs were estimated using the NEMO model, and GHG emissions were taken from reports to the UN Framework Convention on Climate Change. For each METS, the variability in phytoplankton biomass (indexed by chlorophyll-
a
concentration, Chl
a
) and abundance of different cell sizes (phy-size) were analyzed at two time periods (2000–2015 and 2007–2015). Estimates of FCO2 at the analyzed EEZs showed high variability among each other and non-negligible values in the context of greenhouse gas emissions. The trends observed at the METS indicated, in some cases, an increase in Chl
a
(e.g., EPEA-Argentina) and a decrease in others (e.g., IMARPE-Peru). Evidence of increasing populations of small size-phytoplankton was observed (e.g., EPEA-Argentina, Ensenada-Mexico), which would affect the carbon export to the deep ocean. These results highlight the relevance of ocean health and its ecosystem service of regulation when discussing carbon net emissions and budgets.
Body mass index (BMI) is a prognostic factor in several cancer types. We investigated the prognostic role of BMI in a large patient cohort with newly diagnosed lung cancer brain metastases (BM) ...between 1990 and 2013. BMI at diagnosis of BM and graded prognostic assessment (GPA) were calculated. Definitions were underweight (BMI <18.50), weight within normal range (BMI 18.50–24.99) and overweight (BMI ≥ 25.00). A total of 624 patients (men 401/624 64.3%; women 223/624 35.7%; median age of 61 range 33–88) were analysed. Histology was non‐small cell lung cancer in 417/622 (66.8%), small cell lung cancer (SCLC) in 205/624 (32.9%) and not otherwise specified in 2/624 (0.3%) patients. About 313/624 (50.2%) had normal BMI, 272/624 (43.5%) were overweight and 39/624 (6.3%) were underweight. Underweight patients had shorter median overall survival (3 months) compared to patients with normal BMI (7 months) and overweight (8 months; p < .001; log rank test). At multivariate analysis, higher GPA class (HR 1.430; 95% cumulative incidence, CI 1.279–1.598; p < .001; Cox regression model), SCLC histology (HR 1.310; 95% CI 1.101–1.558) and presence of underweight (HR 1.845; 95% CI 1.317–2.585; p = .014; Cox regression model) were independent prognostic factors. Underweight at diagnosis of BM in lung cancer is associated with an unfavourable prognosis.
Objective
This study examined the presence of posttraumatic stress disorder (PTSD) as a predictor of treatment response to dialectical behavior therapy (DBT) across the primary outcomes of interest ...within DBT (i.e., borderline personality disorder BPD symptoms, deliberate self‐harm, emotion regulation ER difficulties) and PTSD symptoms.
Method
Participants (N = 56) were consecutive admissions to an outpatient DBT clinic that completed diagnostic interviews at intake and self‐report outcome measures at intake and every 3 months throughout the treatment.
Results
Patients with (vs. without) a PTSD diagnosis did not report greater clinical severity at intake on most outcome measures, with the exception of PTSD symptom severity and, among older patients only, ER difficulties. The presence of a PTSD diagnosis was not associated with poorer treatment response to DBT. Instead, PTSD was associated with better response on the measure of BPD symptom severity.
Conclusions
The results suggest that patients with PTSD can benefit from DBT.
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