Transcriptome analysis of SerpinB2-deficient breast tumors provides insight into deciphering SerpinB2-mediated roles in breast cancer progression

Background SerpinB2 is highly expressed in immune and tumor cells and is involved in multiple biological functions, including cell survival and remodeling for disease progression. This study prepared SerpinB2-deficient mice and analyzed the differentially expressed genes (DEGs) to determine if loss of this protein delays mammary tumor progression. Results A total of 305 DEGs (75 upregulated and 230 downregulated; > 1.5-fold difference, P < 0.05) were identified in SB2−/−;PyMT tumors compared with PyMT tumors. The DEGs were mainly involved in immune and inflammatory responses related to T cell differentiation, IFN-γ production, and lymphocyte chemotaxis based on 61 enriched GO terms, hierarchical clustering, KEGG pathways, and a functionally grouped annotation network. The significantly changed DEGs (Anxa3, Ccl17, Cxcl13, Cxcr3, IFN-γ, Nr4a1, and Sema3a) annotated with at least two GO categories in SB2−/−;PyMT tumors was validated by qRT-PCR. Conclusions SerpinB2 deficiency alters the expression of multiple genes in mammary tumors, which might cause a delay in PyMT-induced mammary tumor progression.This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and future Planning (2015R1A2A1A05001860)

Experimental observation of hidden Berry curvature in inversion-symmetric bulk 2H-WSe2

We investigate the hidden Berry curvature in bulk 2H-WSe2 by utilizing the surface sensitivity of angle resolved photoemission (ARPES). The symmetry in the electronic structure of transition metal dichalcogenides is used to uniquely determine the local orbital angular momentum (OAM) contribution to the circular dichroism (CD) in ARPES. The extracted CD signals for the K and K' valleys are almost identical but their signs, which should be determined by the valley index, are opposite. In addition, the sign is found to be the same for the two spin-split bands, indicating that it is independent of spin state. These observed CD behaviors are what are expected from Berry curvature of a monolayer of WSe2. In order to see if CD-ARPES is indeed representative of hidden Berry curvature within a layer, we use tight binding analysis as well as density functional calculation to calculate the Berry curvature and local OAM of a monolayer WSe2. We find that measured CD-ARPES is approximately proportional to the calculated Berry curvature as well as local OAM, further supporting our interpretation.Comment: 6 pages, 3 figure

Planalto barrosão

O concelho de Montalegre, situado no planalto Barrosão, é uma das regiões mais remotas e isoladas de Portugal Continental. É um território com baixa densidade populacional, em que cerca de um quarto da superfície do concelho se situa dentro do Parque Nacional da Peneda Gerês, a elevada altitude. É sobre este circunstancialismo geográfico, que permitiu preservar uma ruralidade vincada, que recai a representação fotográfica de paisagem do Planalto do Barroso. É uma representação da paisagem como uma construção cultural e pretende questionar as fronteiras de uma paisagem protegida e como se relaciona com questões de identidade e património.Montalegre, in the Northeast of Portugal, is one of the most remote and isolated areas of the country. The region is an important part of a National Park, the Peneda Geres, located at high altitude and with a very low level of human occupation. This geographic aspect, that led to the preservation and observation of a strong rurality, allowed a photographic representation of the landscape in Barroso´s Plateaus. It’s a photographic representation of the landscape as a cultural construction, questioning the frontiers of a protected landscape and how it relates to heritage and identity

Deep learning-based statistical noise reduction for multidimensional spectral data

In spectroscopic experiments, data acquisition in multi-dimensional phase space may require long acquisition time, owing to the large phase space volume to be covered. In such case, the limited time available for data acquisition can be a serious constraint for experiments in which multidimensional spectral data are acquired. Here, taking angle-resolved photoemission spectroscopy (ARPES) as an example, we demonstrate a denoising method that utilizes deep learning as an intelligent way to overcome the constraint. With readily available ARPES data and random generation of training data set, we successfully trained the denoising neural network without overfitting. The denoising neural network can remove the noise in the data while preserving its intrinsic information. We show that the denoising neural network allows us to perform similar level of second-derivative and line shape analysis on data taken with two orders of magnitude less acquisition time. The importance of our method lies in its applicability to any multidimensional spectral data that are susceptible to statistical noise.Comment: 8 pages, 8 figure

Breast cancer cell debris diminishes therapeutic efficacy through heme oxygenase-1-mediated inactivation of M1-like tumor-associated macrophages

Chemotherapy is commonly used as a major therapeutic option for breast cancer treatment, but its efficacy is often diminished by disruption of patient's anti-tumor immunity. Chemotherapy-generated tumor cell debris could hijack accumulated tumor-associated macrophages (TAMs), provoking tumor recurrence. Therefore, reprogramming TAMs to acquire an immunocompetent phenotype is a promising strategy to potentiate therapeutic efficacy. In this study, we analyzed the proportion of immune cells in the breast cancer patients who received chemotherapy. To validate our findings in vivo, we used a syngeneic murine breast cancer (4T1) model. Chemotherapy generates an immunosuppressive tumor microenvironment in breast cancer. Here, we show that phagocytic engulfment of tumor cell debris by TAMs reduces chemotherapeutic efficacy in a 4T1 breast cancer model. Specifically, the engulfment of tumor cell debris by macrophages reduced M1-like polarization through heme oxygenase-1 (HO-1) upregulation. Conversely, genetic or pharmacologic inhibition of HO-1 in TAMs restored the M1-like polarization. Our results demonstrate that tumor cell debris-induced HO-1 expression in macrophages regulates their polarization. Inhibition of HO-1 overexpression in TAMs may provoke a robust anti-tumor immune response, thereby potentiating the efficacy of chemotherapy.

Factors associated with late recurrence after completion of 5-year adjuvant tamoxifen in estrogen receptor positive breast cancer

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background Recent large trials have shown the survival benefits of 10-year use of tamoxifen by reducing late recurrence compared with 5-year therapy in estrogen receptor(ER)-positive breast cancer. We tried to identify clinical factors associated with the late recurrence. Methods We reviewed our database of ER-positive patients who had received operations between 1996 and 2006 in two institutions. We selected 444 who had completed 5-year tamoxifen and were disease-free up to 10 years after the operation. Patients who had received aromatase inhibitors with any regimens were excluded. As a late recurrence group, 139 patients were identified who had completed 5-year tamoxifen, but had recurrence afterwards. Among them, 61 had local/contralateral breast recurrence and 78 had distant metastasis. The median follow-up was 9.7 years. Clinicopathological factors at the time of initial operation, such as age, menopausal status, progesterone receptor expression, HER2 status, tumor grade and Ki-67, were compared between the disease-free group and the late recurrence group. Results In a univariate analysis, tumor size (>2 cm), lymph node metastasis and high histologic grade were significantly associated with late recurrences (p < 0.05). In a multivariate analysis, only axillary lymph node metastasis was significant (p < 0.001). Late distant metastasis was significantly associated with tumor size and axillary lymph node metastasis (p = 0.038, p < 0.001,respectively). Late local/contralateral breast recurrence was associated with axillary lymph node metastasis (p = 0.042). Conclusions Our data showed axillary lymph node metastasis at initial operation was the only risk factor of late recurrence after completion of tamoxifen for 5 years. Our results can be helpful in making decisions to use extended tamoxifen beyond 5 years

Sign-tunable anomalous Hall effect induced by two-dimensional symmetry-protected nodal structures in ferromagnetic perovskite oxide thin films

Magnetism and spin-orbit coupling (SOC) are two quintessential ingredients underlying novel topological transport phenomena in itinerant ferromagnets. When spin-polarized bands support nodal points/lines with band degeneracy that can be lifted by SOC, the nodal structures become a source of Berry curvature; this leads to a large anomalous Hall effect (AHE). Contrary to three-dimensional systems that naturally host nodal points/lines, two-dimensional (2D) systems can possess stable nodal structures only when proper crystalline symmetry exists. Here we show that 2D spin-polarized band structures of perovskite oxides generally support symmetry-protected nodal lines and points that govern both the sign and the magnitude of the AHE. To demonstrate this, we performed angle-resolved photoemission studies of ultrathin films of SrRuO$_3$, a representative metallic ferromagnet with SOC. We show that the sign-changing AHE upon variation in the film thickness, magnetization, and chemical potential can be well explained by theoretical models. Our study is the first to directly characterize the topological band structure of 2D spin-polarized bands and the corresponding AHE, which could facilitate new switchable devices based on ferromagnetic ultrathin films