bluuebunny/crossref_metadata_2025 huggingface dataset:
SHMT2 Desuccinylation by SIRT5 Drives Cancer Cell Proliferation
Authors: Yang Xin , Wang Zhe , Li Xin , Liu Boya , Liu Minghui , Liu Lu , Chen Shuaiyi , Ren Mengmeng , Wang Yankun , Yu Miao , Wang Bo , Zou Junhua , Zhu Wei-Guo , Yin Yuxin , Gu Wei , Luo Jianyuan
Published: November 2017

The mitochondrial serine hydroxymethyltransferase SHMT2, which catalyzes the rate-limiting step in serine catabolism, drives cancer cell proliferation, but how this role is regulated is undefined. Here, we report that the sirtuin SIRT5 desuccinylates SHMT2 to increase its activity and drive serine catabolism in tumor cells. SIRT5 interaction directly mediated desuccinylation of lysine 280 on SHMT2, which was crucial for activating its enzymatic activity. Conversely, hypersuccinylation of SHMT2 at lysine 280 was sufficient to inhibit its enzymatic activity and downregulate tumor cell growth in vitro and in vivo. Notably, SIRT5 inactivation led to SHMT2 enzymatic downregulation and to abrogated cell growth under metabolic stress. Our results reveal that SHMT2 desuccinylation is a pivotal signal in cancer cells to adapt serine metabolic processes for rapid growth, and they highlight SIRT5 as a candidate target for suppressing serine catabolism as a strategy to block tumor growth.

Significance: These findings reveal a novel mechanism for controlling cancer cell proliferation by blocking serine catabolism, as a general strategy to impede tumor growth. Cancer Res; 78(2); 372–86. ©2017 AACR.
Vitamin C Sensitizes Melanoma to BET Inhibitors
Authors: Mustafi Sushmita , Camarena Vladimir , Volmar Claude-Henry , Huff Tyler C. , Sant David W. , Brothers Shaun P. , Liu Zhao-Jun , Wahlestedt Claes , Wang Gaofeng
Published: November 2017

Bromodomain and extraterminal inhibitors (BETi) are promising cancer therapies, yet prominent side effects of BETi at effective doses have been reported in phase I clinical trials. Here, we screened a panel of small molecules targeting epigenetic modulators against human metastatic melanoma cells. Cells were pretreated with or without ascorbate (vitamin C), which promotes DNA demethylation and subsequently changes the sensitivity to drugs. Top hits were structurally unrelated BETi, including JQ1, I-BET151, CPI-203, and BI-2536. Ascorbate enhanced the efficacy of BETi by decreasing acetylation of histone H4, but not H3, while exerting no effect on the expression of BRD proteins. Histone acetyltransferase 1 (HAT1), which catalyzes H4K5ac and H4K12ac, was downregulated by ascorbate mainly via the TET-mediated DNA hydroxymethylation pathway. Loss of H4ac, especially H4K5ac and H4K12ac, disrupted the interaction between BRD4 and H4 by which ascorbate and BETi blocked the binding of BRD4 to acetylated histones. Cotreatment with ascorbate and JQ1 induced apoptosis and inhibited proliferation of cultured melanoma cells. Ascorbate deficiency as modeled in Gulo−/− mice diminished the treatment outcome of JQ1 for melanoma tumorgraft. In contrast, ascorbate supplementation lowered the effective dose of JQ1 needed to successfully inhibit melanoma tumors in mice. On the basis of our findings, future clinical trials with BETi should consider ascorbate levels in patients. Furthermore, ascorbate supplementation might help reduce the severe side effects that arise from BETi therapy by reducing the dosage necessary for treatment.

Significance: This study shows that ascorbate can enhance the efficacy of BET inhibitors, providing a possible clinical solution to challenges arising in phase I trials from the dose-dependent side effects of this class of epigenetic therapy. Cancer Res; 78(2); 572–83. ©2017 AACR.
Novel BAFF-Receptor Antibody to Natively Folded Recombinant Protein Eliminates Drug-Resistant Human B-cell Malignancies In Vivo
Authors: Qin Hong , Wei Guowei , Sakamaki Ippei , Dong Zhenyuan , Cheng Wesley A. , Smith D. Lynne , Wen Feng , Sun Han , Kim Kunhwa , Cha Soungchul , Bover Laura , Neelapu Sattva S. , Kwak Larry W.
Published: November 2017

Purpose: mAbs such as anti-CD20 rituximab are proven therapies in B-cell malignancies, yet many patients develop resistance. Novel therapies against alternative targets are needed to circumvent resistance mechanisms. We sought to generate mAbs against human B-cell–activating factor receptor (BAFF-R/TNFRSF13C), which has not yet been targeted successfully for cancer therapy.

Experimental Design: Novel mAbs were generated against BAFF-R, expressed as a natively folded cell surface immunogen on mouse fibroblast cells. Chimeric BAFF-R mAbs were developed and assessed for in vitro and in vivo monotherapy cytotoxicity. The chimeric mAbs were tested against human B-cell tumor lines, primary patient samples, and drug-resistant tumors.

Results: Chimeric antibodies bound with high affinity to multiple human malignant B-cell lines and induced potent antibody-dependent cellular cytotoxicity (ADCC) against multiple subtypes of human lymphoma and leukemia, including primary tumors from patients who had relapsed after anti-CD20 therapy. Chimeric antibodies also induced ADCC against ibrutinib-resistant and rituximab-insensitive CD20-deficient variant lymphomas, respectively. Importantly, they demonstrated remarkable in vivo growth inhibition of drug-resistant tumor models in immunodeficient mice.

Conclusions: Our method generated novel anti–BAFF-R antibody therapeutics with remarkable single-agent antitumor effects. We propose that these antibodies represent an effective new strategy for targeting and treating drug-resistant B-cell malignancies and warrant further development. Clin Cancer Res; 24(5); 1114–23. ©2017 AACR.
Small-Cell Carcinomas of the Bladder and Lung Are Characterized by a Convergent but Distinct Pathogenesis
Authors: Chang Matthew T. , Penson Alexander , Desai Neil B. , Socci Nicholas D. , Shen Ronglai , Seshan Venkatraman E. , Kundra Ritika , Abeshouse Adam , Viale Agnes , Cha Eugene K. , Hao Xueli , Reuter Victor E. , Rudin Charles M. , Bochner Bernard H. , Rosenberg Jonathan E. , Bajorin Dean F. , Schultz Nikolaus , Berger Michael F. , Iyer Gopa , Solit David B. , Al-Ahmadie Hikmat A. , Taylor Barry S.
Published: November 2017

Purpose: Small-cell carcinoma of the bladder (SCCB) is a rare and aggressive neuroendocrine tumor with a dismal prognosis and limited treatment options. As SCCB is histologically indistinguishable from small-cell lung cancer, a shared pathogenesis and cell of origin has been proposed. The aim of this study is to determine whether SCCBs arise from a preexisting urothelial carcinoma or share a molecular pathogenesis in common with small-cell lung cancer.

Experimental Design: We performed an integrative analysis of 61 SCCB tumors to identify histology- and organ-specific similarities and differences.

Results: SCCB has a high somatic mutational burden driven predominantly by an APOBEC-mediated mutational process. TP53, RB1, and TERT promoter mutations were present in nearly all samples. Although these events appeared to arise early in all affected tumors and likely reflect an evolutionary branch point that may have driven small-cell lineage differentiation, they were unlikely the founding transforming event, as they were often preceded by diverse and less common driver mutations, many of which are common in bladder urothelial cancers, but not small-cell lung tumors. Most patient tumors (72%) also underwent genome doubling (GD). Although arising at different chronologic points in the evolution of the disease, GD was often preceded by biallelic mutations in TP53 with retention of two intact copies.

Conclusions: Our findings indicate that small-cell cancers of the bladder and lung have a convergent but distinct pathogenesis, with SCCBs arising from a cell of origin shared with urothelial bladder cancer. Clin Cancer Res; 24(8); 1965–73. ©2017 AACR.

See related commentary by Oser and Jänne, p. 1775
Pazopanib-Induced Cutaneous Leukocytoclastic Vasculitis: An Exclusion Diagnosis of a Multidisciplinary Approach
Authors: Alpuim Costa Diogo , Baptista de Almeida Susana , Coelho Barata Pedro , Quintela António , Cabral Pedro , Afonso Ana , Maia Silva João
Published: November 2017

In phase II/III trials, cutaneous side effects of pazopanib were reported in less than 20% of patients, with only 1–3% being grade 3/4. We present a case of a 66-year-old man with a previous history of left nephrectomy for a stage II clear cell renal carcinoma. Approximately 18 months later, recurrent disease in the lungs, mediastinum, and left psoas and bulky abdominal/pelvic nodal metastasis were documented. He was initially treated with pazopanib 800 mg q.d. and 1 week after starting this therapy, the patient presented with palpable purpura on his ankles. These lesions regressed within 2 weeks off pazopanib, but had recurred 4 weeks after he resumed medication at 400 mg q.d. Biopsy of the lesions revealed leukocytoclastic vasculitis. Despite tumour response to therapy, pazopanib was discontinued with total resolution of this skin toxicity within 2 weeks of his cutaneous toxicity. To the best of our knowledge, we report a rare yet significant cutaneous adverse reaction to pazopanib.
Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report
Authors: Fakhri Ghina , Akel Reem , Salem Ziad , Tawil Ayman , Tfayli Arafat
Published: November 2017

Background: Pembrolizumab is a humanized monoclonal antibody which serves to enhance the antitumor immune response by targeting programmed cell death 1 receptor. The use of pembrolizumab plus carboplatin/pemetrexed combination therapy results in improvement in overall survival and progression-free survival rates for non-small cell lung cancer (NSCLC) patients as compared to chemotherapy alone. However, numerous immune-mediated toxicities of pembrolizumab have been reported. Case Presentation: We report the case of a 74-year-old male patient diagnosed with stage IIIA programmed death-ligand 1-positive non-small cell lung adenocarcinoma treated with 4 cycles of carboplatin/pemetrexed plus pembrolizumab combination therapy followed by 2 cycles of pembrolizumab treatment. Follow-up PET-CT scanning showed a very good response at the level of the tumor but new-onset activity in bilateral hilar and mediastinal lymph nodes. Biopsy of these lymph nodes revealed a benign pathology with noncaseating granulomas consistent with immune-mediated sarcoidosis. Conclusion: The pathogenesis of immunotherapy-induced sarcoidosis is not yet known but has been reported in different cancers and using different checkpoint inhibitors. To our knowledge, this case is the first in the literature displaying pulmonary sarcoidosis in a patient with NSCLC 4 months after having initiated chemotherapy plus pembrolizumab combination therapy.
Metastatic Urothelial Carcinoma with Glandular Differentiation That Confirmed the Response by Autopsy Specimen to Second-Line mFOLFOX6 (Fluorouracil, Oxaliplatin, and Leucovorin) plus Bevacizumab Chemotherapy
Authors: Naiki Taku , Etani Toshiki , Naiki-Ito Aya , Fujii Kana , Ando Ryosuke , Iida Keitaro , Nagai Takashi , Sugiyama Yosuke , Nakagawa Motoo , Kawai Noriyasu , Yasui Takahiro
Published: November 2017

The prognostic significance of glandular differentiation in urothelial carcinoma (UC) is controversial, and thus far there is no established treatment strategy against metastasis of glandular component. We describe here a case of metastatic UC with glandular differentiation that had histological disappearance of adenocarcinoma components at autopsy after sequential chemotherapy with S-1 and cisplatin (CDDP) and with mFOLFOX6 (fluorouracil, oxaliplatin, and leucovorin) plus bevacizumab (mFOLFOX6+Bev). A 62-year-old Asian male was diagnosed with invasive UC with glandular differentiation (T2N0M0) by radical cystectomy and ileal conduit, and careful follow-up observation was made. Eight years after radical operation, peritoneal metastases occurred, and a biopsy specimen using colon fiber revealed high-grade adenocarcinomas with an immunohistochemical profile that included positivity for cytokeratin 7 (CK7) and negativity for cytokeratin 20 (CK20) and uroplakin, which was identical to the radical cystectomy specimen. Thus, he received combination chemotherapy consisting of S-1 and CDDP; however, the peritoneal metastasis worsened after 2 cycles. Therefore, second-line mFOLFOX6+Bev chemotherapy was performed for a total of 5 courses. In spite of this, the patient died, and the final diagnosis by autopsy was multiple metastases of infiltrating pure UC to the lung, bone, and peritoneum. Interestingly, there were no pathological findings of adenocarcinoma, and the immunohistochemical profile of the metastatic lesions was identical to that of the previous specimens from the bladder and colon. This suggests that sequential chemotherapy of S-1 and CDDP and second-line mFOLFOX6+Bev might be a feasible option in metastatic UC with glandular differentiation.
Alteration of Tight Junction Protein Expression in Dahl Salt-Sensitive Rat Kidney
Authors: Jo Chor Ho , Kim Sua , Oh Il Hwan , Park Joon-Sung , Kim Gheun-Ho
Published: November 2017

Background/Aims: Altered pressure natriuresis is an important mechanism of hypertension, but it remains elusive at the molecular level. We hypothesized that in the kidney, tight junctions (TJs) may have a role in pressure natriuresis because paracellular NaCl transport affects interstitial hydrostatic pressure. Methods: To assess the association of salt-sensitive hypertension with altered renal TJ protein expression, Dahl salt-sensitive (SS) and salt-resistant (SR) rats were put on an 8% NaCl-containing rodent diet for 4 weeks. Systolic blood pressure (SBP) and urine NaCl excretion were measured weekly, and kidneys were harvested for immunoblotting and quantitative PCR analysis at the end of the animal experiments. Results: SBP was significantly higher in SS rats than in SR rats during the first to fourth weeks of the animal experiments. During the first and second week, urinary NaCl excretion was significantly lower in SS rats as compared with SR rats. However, the difference between the two groups vanished at the third and fourth weeks. In the kidney, claudin-4 protein and mRNA were significantly increased in SS rats as compared with SR rats. On the other hand, occludin protein and mRNA were significantly decreased in SS rats as compared with SR rats. The expression of claudin-2, claudin-7, and claudin-8 did not vary significantly between the two groups. Conclusions: In SS rats, SS hypertension was associated with differential changes in renal TJ protein expression. Both upregulation of claudin-4 and downregulation of occludin might increase paracellular NaCl transport in the kidney, resulting in impaired pressure natriuresis in SS rats.
Long Non-Coding RNA H19 Protects H9c2 Cells against Hypoxia-Induced Injury by Targeting MicroRNA-139
Authors: Gong Li-Cheng , Xu Hai-Ming , Guo Gong-Liang , Zhang Tao , Shi Jing-Wei , Chang Chang
Published: November 2017

Background/Aims: Acute myocardial infarction (AMI) occurs when blood supply to the heart is diminished (ischemia) for long time; ischemia is primarily caused due to hypoxia. The present study evaluated the effects of long non-coding RNA H19 on hypoxic rat H9c2 cells and mouse HL-1 cells. Methods: Hypoxic injury was confirmed by measuring cell viability, migration and invasion, and apoptosis using MTT, Transwell and flow cytometry assays, respectively. H19 expression after hypoxia was estimated by qRT-PCR. We then measured the effects of non-physiologically expressed H19, knockdown of miR-139 with or without H19 silence, and abnormally expressed Sox8 on hypoxia-induced H9c2 cells. Moreover, the interacted miRNA for H19 and downstream target gene were virtually screened and verified. The involved signaling pathways and the effects of abnormally expressed H19 on contractility of HL-1 cells were explored via Western blot analysis. Results: Hypoxia induced decreases of cell viability, migration and invasion, increase of cell apoptosis and up-regulation of H19. Knockdown of H19 increased hypoxia-induced injury in H9c2 cells. H19 acted as a sponge for miR-139 and H19 knockdown aggravated hypoxia-induced injury by up-regulating miR-139. Sox8 was identified as a target of miR-139, and its expression was negatively regulated by miR-139. The mechanistic studies revealed that overexpression of Sox8 might decrease hypoxia-induced cell injury by activating the PI3K/AKT/mTOR pathway and MAPK. Besides, H19 promoted contractility of HL-1 cells. Conclusion: These findings suggest that H19 alleviates hypoxia-induced myocardial cell injury by miR-139-mediated up-regulation of Sox8, along with activation of the PI3K/AKT/mTOR pathway and MAPK.
LukS-PV-Regulated MicroRNA-125a-3p Promotes THP-1 Macrophages Differentiation and Apoptosis by Down-Regulating NF1 and Bcl-2
Authors: Sun Xiao-Xi , Zhang Shan-Shan , Dai Chun-Yang , Peng Jing , Pan Qing , Xu Liang-Fei , Ma Xiao-Ling
Published: November 2017

Background/Aims: LukS-PV is a component of Panton-Valentine leukocidin (PVL). We have previously demonstrated that LukS-PV potently promoted differentiation and induced apoptosis in THP-1 cells. However, the precise mechanisms of these actions remain unknown. MicroRNAs (miRs) play important roles in cellular differentiation and apoptosis. This study aimed to investigate the role of miR-125a-3p in LukS-PV-regulated differentiation and apoptosis and its underlying mechanism in THP-1 cells. Methods: MicroRNA profiling analyses were conducted to determine differential miRNA expression levels in THP-1 cells treated with LukS-PV. Cell differentiation and apoptosis were measured in THP-1 cells by gain-of-function and loss-of-function experiments. Bioinformatics analysis and luciferase reporter assays were used to confirm the targets of miR-125a-3p. The effects of the miR-125a-3p targets on cellular differentiation were determined by knocking them down. Results: MiR-125a-3p was up-regulated after treating the human monocytic leukaemia cell line THP-1 with LukS-PV. In addition, miR-125a-3p positively regulated apoptosis and differentiation in THP-1 cells treated with LukS-PV. Concordantly, luciferase reporter assays confirmed that neurofibromatosis type 1 (NF1) and B-cell lymphoma 2 (Bcl-2) were direct target genes of miR-125a-3p. Moreover, NF1 knockdown in THP-1 cells significantly promoted differentiation in vitro. Finally, the extracellular signal-regulated kinase (ERK) pathway, a downstream target of NF1, was activated after NF1 knockdown. Conclusions: These findings confirm that miR-125a-3p is involved in LukS-PV-mediated cell differentiation and apoptosis in THP-1 cells.
Heat Shock Protein 70 Negatively Regulates TGF-β-Stimulated VEGF Synthesis via p38 MAP Kinase in Osteoblasts
Authors: Sakai Go , Tokuda Haruhiko , Fujita Kazuhiko , Kainuma Shingo , Kawabata Tetsu , Matsushima-Nishiwaki Rie , Kozawa Osamu , Otsuka Takanobu
Published: November 2017

Background/Aims: We previously demonstrated that transforming growth factor-β (TGF-β) stimulates the synthesis of vascular endothelial growth factor (VEGF) through the activation of p38 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. Heat shock protein70 (HSP70) is a ubiquitously expressed molecular chaperone. In the present study, we investigated the involvement of HSP70 in the TGF-β-stimulated VEGF synthesis and the underlying mechanism in these cells. Methods: Culture MC3T3-E1 cells were stimulated by TGF-β. Released VEGF was measured using an ELISA assay. VEGF mRNA level was quantified by RT-PCR. Phosphorylation of each protein kinase was analyzed by Western blotting. Results: VER-155008 and YM-08, both of HSP70 inhibitors, significantly amplified the TGF-β-stimulated VEGF release. In addition, the expression level of VEGF mRNA induced by TGF-β was enhanced by VER-155008. These inhibitors markedly strengthened the TGF-β-induced phosphorylation of p38 MAP kinase. The TGF-β-induced phosphorylation of p38 MAP kinase was amplified in HSP70-knockdown cells. SB203580, an inhibitor of p38 MAP kinase, significantly suppressed the amplification by these inhibitors of the TGF-β-induced VEGF release. Conclusion: These results strongly suggest that HSP70 acts as a negative regulator in the TGF-β-stimulated VEGF synthesis in osteoblasts, and that the inhibitory effect of HSP70 is exerted at a point upstream of p38 MAP kinase.
Potential Regulatory Effects of Corticotropin-Releasing Factor on Tight Junction-Related Intestinal Epithelial Permeability are Partially Mediated by CK8 Upregulation
Authors: Yue Hu , Bin Lu  , Chaoying Chen , Meng Zhang , Meng Li , Xi Wang
Published: November 2017

Background/Aims: Intestinal permeability and stress have been implicated in the pathophysiology of irritable bowel syndrome (IBS). Cytokeratin 8 (CK8), for the first time, has been shown to mediate corticotropin-releasing factor (CRF)-induced changes in intestinal permeability in animal models of IBS. In this study, we investigated the regulatory effects of CRF on the permeability of human intestinal epithelial cells through the CK8-mediated tight junction. Methods: The expression levels of corticotropin-releasing factor receptor 1 (CRFR1) and corticotropin-releasing factor receptor 2 (CRFR2) on the HT29 cell surface were determined by immunofluorescence, RT-PCR, and Western blotting. After treatment with 100 nM CRF for 72 h, the translocation of FITC-labelled dextran was measured in a transwell chamber; the structural changes of tight junctions were observed under transmission electron microscopy; the expression levels of CK8, F-actin and tight junction proteins ZO-1, claudin-1, and occludin were detected by immunoblotting and immunofluorescence. The activity of RhoA was detected by immunoprecipitation. Furthermore, the effects of CRF on intestinal epithelial permeability were examined in CK8-silenced HT29 cells, which were constructed by shRNA interference. Results: CRF treatment increased FITC-labelled dextran permeability, caused the opening of tight junctions, induced increased fluorescence intensity of CK8 and decreased the intensities of ZO-1, claudin-1, and occludin, together with structural disruption. The expression levels of F-actin, occludin, claudin-1, and ZO-1 were downregulated. RhoA activity peaked at 30 min after CRF treatment. CRF-induced increased permeability, and downregulation of claudin-1 and occludin were not blocked by CK8 silencing. Nevertheless, CK8 silencing blocked the effects of CRF regarding the decrease in the expression levels of F-action and ZO-1 and increase in RhoA activity. Conclusion: CRF may increase intestinal epithelial permeability by upregulating CK8 expression, activating the RhoA signalling pathway, promoting intestinal epithelial actin remodelling, and decreasing the expression of the tight junction protein ZO-1. Other CK8-independent pathways may be involved in the downregulation of claudin-1 and occludin, which might also contribute to increased intestinal epithelial permeability.
VEGF-A/Neuropilin 1 Pathway Confers Cancer Stemness via Activating Wnt/β-Catenin Axis in Breast Cancer Cells
Authors: Zhang Lansheng , Wang Hongmei , Li Caihong , Zhao Yang , Wu Langjie , Du Xiuping , Han Zhengxiang
Published: November 2017

Background/Aims: Targeting cancer stem cells (CSCs) is emerging as a promising method for cancer treatment. We previously indicated that knockdown of Neuropilin 1(NRP-1) could inhibit breast cancer cell proliferation. Here, we continue exploring the roles and mechanisms of VEGF-A/NRP-1 axis in breast CSCs formation. Methods: qRT-PCR was used to detect the levels of VEGF-A and NRP-1 in breast cancer sphere cells and wild-type cells. Mammospheres formation, flow cytometry, soft agar colony and tumor formation assays were performed to evaluate the effects of VEGF-A/NRP-1 on breast cancer stemness. Further HUVECs tube formation, cell invasion assays were carried out to detect the effects of VEGF-A/NRP-1 on breast cancer spheres-induced angiogenesis. Finally, Annexin V/PI apoptosis and CCK8 assays were used to detect the effects of VEGF-A/NRP-1 on chemoresistance. Results: Overexpression of VEGF-A or NRP-1 conferred CSCs-related traits in MCF-7 cells, while knockdown of VEGF-A or NRP-1 reduced CSCs-related traits in MDA-MB-231 cells in vitro and in vivo. Notably, VEGF-A acted in a NRP-1 dependent way. Mechanistically, the VEGF-A/NRP-1 axis conferred CSCs phenotype via activating Wnt/β-catenin pathway. Conclusion: our results suggest that VEGF-A/NRP-1 axis could confer CSCs-related traits and chemoresistance.
O arcabouço estrutural da Bacia Sedimentar do Araripe, Província Borborema, baseado em dados aeromagnetométricos
Authors: Camacho Clyvihk Renna , Sousa Frederico Ricardo Ferreira Rodrigues de Oliveira e
Published: November 2017

Este trabalho apresenta uma interpretação atualizada da estruturação interna da Bacia Sedimentar do Araripe, localizada ao sul da porção setentrional da Província Borborema, por meio do processamento e da análise de dados aerogeofísicos de magnetometria pertencentes à Companhia de Pesquisa de Recursos Minerais – Serviço Geológico do Brasil. Essa bacia é reconhecida como um conjunto de meio-grábens assimétricos, fragmentados por altos de embasamento e complexos sistemas de falhas e lineamentos E-W a NE-SW, associados ao trend estrutural do Orógeno Borborema, e NW-SE, relacionados a processos extencionais cuja evolução poderia estar associada ao rift-valley na extremidade norte do rift abortado da Bacia do Recôncavo. A partir da imagem geofísica do campo magnético anômalo foram extraídas suas derivadas de primeira ordem nas direções x, y, z, seu gradiente horizontal total, sua amplitude do sinal analítico (ASA) e inclinação do sinal analítico. A deconvolução de Euler foi aplicada ao grid ASA, o que permitiu uma aproximação da posição horizontal e estimativa da profundidade do topo das principais fontes magnéticas. A análise conjunta dos diversos mapas gerados permitiu uma interpretação regional dos domínios e lineamentos magnéticos, os quais foram associados às principais estruturas em subsuperfície que compõem o arcabouço da bacia. Os resultados demonstram que a compartimentação estrutural da Bacia Sedimentar do Araripe é muito mais complexa do que a descrita anteriormente por outros autores. O padrão estrutural da bacia apresenta variação lateral, de W para E, conforme demonstrado pela divisão dos domínios magnéticos, indicando haver variações substanciais na espessura das rochas sedimentares, com áreas mais espessas a E e mais rasas a W.
Geologia e petrologia do Granito São Vicente na região do Parque Estadual Águas Quentes, estado de Mato Grosso, Brasil
Authors: Guimarães Giulia Barbosa Trivelli , Pierosan Ronaldo , Ruiz Amarildo Salina
Published: November 2017

A análise petrogenética das rochas hipabissais do Granito São Vicente na região do Parque Estadual Águas Quentes permitiu o reconhecimento e a caracterização de distintas fácies. A partir de critérios petrográficos, foram individualizadas quatro fácies, todas de natureza isotrópica: sienogranito grosso (textura equigranular a inequigranular, leucocrática); aplito porfirítico (textura inequigranular fina a média com fenocristais, leucocrática, sienogranítica); microgranito (textura microporfirítica com microfenocristais em matriz fanerítica muito fina, textura micrográfica frequente, sienogranítica); e riolito porfirítico (textura porfirítica e glomeroporfirítica em matriz afanítica a fanerítica muito fina). As fácies aplito porfirítico e microgranito são características de cúpulas graníticas epizonais. A fácies riolito porfirítico tem relação com diques hipabissais. O padrão de distribuição dos elementos terras raras (ETRs) indica um forte fracionamento de ETRs leves, com razões LaN/SmN médias de 7,87, anomalia negativa de Eu (Eu/Eu* ~0,38) e enriquecimento de ETRs pesados, expressos por razões GdN/YbN menores que a unidade (~0,82). A distribuição dos elementos em diagramas binários e as anomalias negativas em diagramas multielementos indicam atuação de processos de cristalização fracionada de fases minerais como plagioclásio, biotita, apatita e zircão para as fácies sienogranito e aplito. Análises U-Pb SHRIMP em zircão mostram idade de 528 ± 4 Ma para o riolito porfirítico, considerada idade de cristalização magmática. Sugere-se que o magma que gerou as rochas plutônicas e hipabissais do Granito São Vicente na região estudada pode ter se originado por um componente de fontes litosféricas previamente afetadas por subducção ou por fontes crustais, com contribuição de fontes astenosféricas como outro componente importante.
Handheld Echocardiography
Authors: Chamsi-Pasha Mohammed A. , Sengupta Partho P. , Zoghbi William A.
Published: November 2017

Echocardiography is the primary imaging modality for diagnosing cardiac conditions. Over the past 2 decades, technological advancements have resulted in the emergence of miniaturized handheld ultrasound equipment that is compact and battery operated, and handheld echocardiography can be readily performed at the point of care with reasonable image quality. The simplicity of use, availability at the patient’s bedside, easy transportability, and relatively low cost have encouraged physicians to use these devices for prompt medical decision making. As a consequence, the use of handheld echocardiography is on the rise even among nonechocardiographers (intensivists, emergency care physicians, internists, and medical students). One of the real utilities of ultrasound-augmented clinical diagnosis is in evaluating patients efficiently and selecting patients for appropriate downstream diagnostic testing including comprehensive echocardiography. Although clinical evidence supports the use of handheld devices in various clinical settings and by different users, proficiency in point-of-care ultrasound requires dedicated training in both performance and interpretation. This review summarizes the existing literature on the use of handheld echocardiography in conducting focused cardiac examinations: its training requirements, challenges, opportunities, and future perspectives in the care of the cardiovascular patient.
Brunellia (Brunelliaceae) in Peru—distribution, a new species and a key
Authors: BÖHNERT TIM , WEIGEND MAXIMILIAN
Published: November 2017

An updated checklist and key to the Peruvian species of Brunellia (Brunelliaceae) is presented based on georeferenced herbarium specimens from Peruvian herbaria, own field collections and online sources. Thirteen Brunellia species are documented as native to Peru, including nine endemic species. Compared to previous studies the average number of Brunellia spp. per Andean department doubles from two to more than four species. Our data indicate a center of species richness and endemism in northern Peru, namely the Amotape-Huancabamba Zone (AHZ). Furthermore, distribution maps for all species are presented. Brunellia ovalifolia is reported as a new record for Peru. Another species, B. lobinii Böhnert & Weigend sp. nov., from Departamento de Lambayeque, Provincia de Ferreñafe, near the town of Kañaris, is here described as new to science. Additionally, some taxonomic uncertainties are discussed.
Introductory Comments
Authors: Sujecka Jolanta
Published: November 2017

Introductory CommentsThe sixth issue (not just in the Thematic Section) is devoted to the borders of civilization in our memory, in culture, in art, in literature, in the arrangement of political objectives. Both their demarcation and their crossing is a matter of the objectives we can and want to set ourselves in the context of the order that exists and into which we try to fit, transforming it or levelling.The value of this survey of  “images of borders” is its setting in such varied material, owing to which the theoretical speculations gain a representative illustration and, at the same time, a guarantee of being rooted, even if it is only a “contact zone”. WprowadzenieSzósty numer (nie tylko sekcja tematyczna) jest poświęcony kwestii granic cywilizacji w naszej pamięci, kulturze, sztuce, literaturze, w definiowaniu celów politycznych. Zarówno ich wyznaczanie, jak i przekraczanie, jest kwestią celów, jakie możemy i chcemy postawić sobie w kontekście istniejącego ładu, w który staramy się wpisać, przekształcając go lub dostosowując się do niego. Wartością niniejszego przeglądu "obrazów granic" jest przedstawienie ich poprzez tak zróżnicowany materiał, dzięki czemu rozważania teoretyczne zyskują reprezentatywną ilustrację, a zarazem gwarancję zakorzenienia, nawet jeśli będzie to tylko "sfera kontaktu".
Northeast China as a Contact Zone in Polish and Serbian Travelogues, 1900-1939
Authors: Ewertowski Tomasz
Published: November 2017

Northeast China as a Contact Zone in Polish and Serbian Travelogues, 1900-1939Historically, Northeast China (Manchuria) was a border zone between China and nomadic peoples, as well as between Russian and Qing empires since the 17th century. In the second half of the 19th century and in the first half of the 20th century, a number of factors (penetration by foreign powers, collapse of the Qing Empire, revolution in Russia, Japanese expansion and demographic changes) transformed this area into “a contact zone” in the sense given by Mary Louise Pratt. The main focus of the article is the way in which this contact zone was described by Polish and Serbian travellers. Their can provide a special outlook, because Poland and Serbia did not participate extensively in the colonial penetration into China, however, Serbs and Poles travelled there, often representing Russian institutions. Therefore they were observing China as agents of imperial force, but they did not identify themselves fully with it. Our analysis of the image of Northeast China as a contact zone will be divided into three broad sections: 1) political and military expansion, 2) economic and demographic relations, 3) transcultural phenomena of everyday life. Chiny Północno-Wschodnie jako strefa kontaktu w polskich i serbskich relacjach podróżniczych w latach 1900-1939Północno-wschodnie Chiny (Mandżuria) są historyczną granicą między Chinami a ludami wędrownymi, od siedemnastego wieku również między Rosją a imperium dynastii Qing. W drugiej połowie dziewiętnastego wieku, a zwłaszcza w pierwszej połowie dwudziestego szereg czynników (penetracja przez obce mocarstwa, upadek dynastii Qing, rewolucja w Rosji, ekspansja japońska i zmiany demograficzne) uczyniły z tego obszaru „strefę kontaktu” w rozumieniu Mary Louise Pratt. Głównym tematem artykułu jest sposób opisu strefy kontaktu przez polskich i serbskich podróżników. Ich dzieła dają bowiem szczególną perspektywę, gdyż Polska i Serbia nie uczestniczyły w kolonialnej penetracji Chin, jednakże Serbowie i Polacy podróżowali do Państwa Środka, często reprezentując rosyjskie instytucje. Z tego względu obserwowali Chiny jako reprezentanci imperium, jednak nie identyfikowali się z nim w pełni. Analiza obrazu północno-wschodnich Chin jako strefy kontaktu dzieli się na trzy sekcje: 1) ekspansja polityczna i militarna, 2) relacje ekonomiczne i demograficzne, 3) zjawiska transkulturowe w życiu codziennym.
The Empire Strikes Back. Russian National Cinema After 2005
Authors: Rawski Tomasz , Roman-Rawska Katarzyna
Published: November 2017

The Empire Strikes Back. Russian National Cinema After 2005The paper provides critical analysis of the latest wave of Russian national cinema (2005-2013), considered one of key instruments of Vladimir Putin’s nation-building cultural policy. The analysis, focused mostly on historical film and war film, reveals the concept of an ‘imperial nation’ as the main concept underlying this policy. The new Russian nation-concept is calculated to binding elements from two former Russian imperial traditions: tradition of the Russian Empire and the Soviet tradition, thus trying to overcome the identity crisis in contemporary Russia. Imperium kontratakuje. Rosyjskie kino narodowe po 2005 rokuArtykuł zajmuje się krytyczną analizą filmów najnowszej fali rosyjskiego kina narodowego (2005-2013), uważanej tu za jedno z kluczowych narzędzi polityki kulturalnej Władimira Putina obliczonej na budowanie narodu. Autorzy artykułu skupiają się przede wszystkim na filmie historycznym i wojennym, odsłaniając pojęcie „imperialnego narodu” jako konceptu stojącego u podstaw oficjalnej polityki. Nowe rosyjskie pojęcie narodu łączy w sobie dwie tradycje rosyjskie: tradycję Imperium Rosyjskiego oraz tradycję Związku Radzieckiego, próbując w ten sposób przezwyciężyć kryzys tożsamościowy współczesnej Rosji.
Broadening of Cloud Droplet Size Spectra by Stochastic Condensation: Effects of Mean Updraft Velocity and CCN Activation
Authors: Sardina Gaetano , Poulain Stéphane , Brandt Luca , Caballero Rodrigo
Published: November 2017

The authors study the condensational growth of cloud droplets in homogeneous isotropic turbulence by means of a large-eddy simulation (LES) approach. The authors investigate the role of a mean updraft velocity and of the chemical composition of the cloud condensation nuclei (CCN) on droplet growth. The results show that a mean constant updraft velocity superimposed onto a turbulent field reduces the broadening of the droplet size spectra induced by the turbulent fluctuations alone. Extending the authors’ previous results regarding stochastic condensation, the authors introduce a new theoretical estimation of the droplet size spectrum broadening that accounts for this updraft velocity effect. A similar reduction of the spectra broadening is observed when the droplets reach their critical size, which depends on the chemical composition of CCN. The analysis of the square of the droplet radius distribution, proportional to the droplet surface, shows that for large particles the distribution is purely Gaussian, while it becomes strongly non-Gaussian for smaller particles, with the left tail characterized by a peak around the haze activation radius. This kind of distribution can significantly affect the later stages of the droplet growth involving turbulent collisions, since the collision probability kernel depends on the droplet size, implying the need for new specific closure models to capture this effect.
Validation of a Statistical Methodology for Extracting Vegetation Feedbacks: Focus on North African Ecosystems in the Community Earth System Model
Authors: Yu Yan , Notaro Michael , Wang Fuyao , Mao Jiafu , Shi Xiaoying , Wei Yaxing
Published: November 2017

Generalized equilibrium feedback assessment (GEFA) is a potentially valuable multivariate statistical tool for extracting vegetation feedbacks to the atmosphere in either observations or coupled Earth system models. The reliability of GEFA at capturing the terrestrial impacts on regional climate is demonstrated here using the National Center for Atmospheric Research Community Earth System Model (CESM), with focus on North Africa. The feedback is assessed statistically by applying GEFA to output from a fully coupled control run. To reduce the sampling error caused by short data records, the traditional or full GEFA is refined through stepwise GEFA by dropping unimportant forcings. Two ensembles of dynamical experiments are developed for the Sahel or West African monsoon region against which GEFA-based vegetation feedbacks are evaluated. In these dynamical experiments, regional leaf area index (LAI) is modified either alone or in conjunction with soil moisture, with the latter runs motivated by strong regional soil moisture–LAI coupling. Stepwise GEFA boasts higher consistency between statistically and dynamically assessed atmospheric responses to land surface anomalies than full GEFA, especially with short data records. GEFA-based atmospheric responses are more consistent with the coupled soil moisture–LAI experiments, indicating that GEFA is assessing the combined impacts of coupled vegetation and soil moisture. Both the statistical and dynamical assessments reveal a negative vegetation–rainfall feedback in the Sahel associated with an atmospheric stability mechanism in CESM versus a weaker positive feedback in the West African monsoon region associated with a moisture recycling mechanism in CESM.
The Influence of Atmospheric Rivers over the South Atlantic on Winter Rainfall in South Africa
Authors: Blamey R. C. , Ramos A. M. , Trigo R. M. , Tomé R. , Reason C. J. C.
Published: November 2017

A climatology of atmospheric rivers (ARs) impinging on the west coast of South Africa (29°–34.5°S) during the austral winter months (April–September) was developed for the period 1979–2014 using an automated detection algorithm and two reanalysis products as input. The two products show relatively good agreement, with 10–15 persistent ARs (lasting 18 h or longer) occurring on average per winter and nearly two-thirds of these systems occurring poleward of 35°S. The relationship between persistent AR activity and winter rainfall is demonstrated using South African Weather Service rainfall data. Most stations positioned in areas of high topography contained the highest percentage of rainfall contributed by persistent ARs, whereas stations downwind, to the east of the major topographic barriers, had the lowest contributions. Extreme rainfall days in the region are also ranked by their magnitude and spatial extent. The results suggest that although persistent ARs are important contributors to heavy rainfall events, they are not necessarily a prerequisite. It is found that around 70% of the top 50 daily winter rainfall extremes in South Africa were in some way linked to ARs (both persistent and nonpersistent). Overall, the findings of this study support similar investigations on ARs in the North Atlantic and North Pacific.
Turbulence Dissipation Rate in the Atmospheric Boundary Layer: Observations and WRF Mesoscale Modeling during the XPIA Field Campaign
Authors: Muñoz-Esparza Domingo , Sharman Robert D. , Lundquist Julie K.
Published: November 2017

A better understanding and prediction of turbulence dissipation rate ε in the atmospheric boundary layer (ABL) is important for many applications. Herein, sonic anemometer data from the Experimental Planetary boundary layer Instrumentation Assessment (XPIA) field campaign (March–May 2015) are used to derive energy dissipation rate (EDR; =) within the first 300 m above the ground employing second-order structure functions. Turbulence dissipation rate is found to be strongly driven by the diurnal evolution of the ABL, presenting a distinct statistical behavior between daytime and nighttime conditions that follows log–Weibull and lognormal distributions, respectively. In addition, the vertical structure of EDR is characterized by a decrease with height above the surface, with the largest gradients occurring within the surface layer (z < 50 m). Convection-permitting mesoscale simulations were carried out with all of the 1.5-order turbulent kinetic energy (TKE) closure planetary boundary layer (PBL) schemes available in the Weather Research and Forecasting (WRF) Model. Overall, the three PBL schemes capture the observed diurnal evolution of EDR as well as the statistical behavior and vertical structure. However, the Mellor–Yamada-type schemes underestimate the large EDR levels during the bulk of daytime conditions, with the quasi-normal scale elimination (QNSE) scheme providing the best agreement with observations. During stably stratified nighttime conditions, Mellor–Yamada–Janjić (MYJ) and QNSE tend to exhibit an artificial “clipping” to their background TKE levels. A reduction in the model constant in the dissipation term for the Mellor–Yamada–Nakanishi–Niino (MYNN) scheme did not have a noticeable impact on EDR estimates. In contrast, application of a postprocessing statistical remapping technique reduced the systematic negative bias in the MYNN results by 75%.
Dramatic Inner-Core Tropopause Variability during the Rapid Intensification of Hurricane Patricia (2015)
Authors: Duran Patrick , Molinari John
Published: November 2017

Dropsondes with horizontal spacing as small as 4 km were released from the stratosphere in rapidly intensifying Hurricane Patricia (2015) during the Office of Naval Research Tropical Cyclone Intensity experiment. These observations provide cross sections of unprecedented resolution through the inner core of a hurricane. On 21 October, Patricia exhibited a strong tropopause inversion layer (TIL) across its entire circulation, with a maximum magnitude of 5.1 K (100 m)−1. This inversion weakened between 21 and 22 October as potential temperature θ increased by up to 16 K just below the tropopause and decreased by up to 14 K in the lower stratosphere. Between 22 and 23 October, the TIL over the eye weakened further, allowing the tropopause to rise by 1 km. Meanwhile over Patricia’s secondary eyewall, the TIL restrengthened and bulged upward by about 700 m into what was previously the lower stratosphere. These observations support many aspects of recent modeling studies, including eyewall penetration into the stratosphere during rapid intensification (RI), the existence of a narrow inflow layer near the tropopause, and the role of subsidence from the stratosphere in developing an upper-level warm core. Three mechanisms of inner-core tropopause variability are hypothesized: destabilization of the TIL through turbulent mixing, weakening of the TIL over the eye through upper-tropospheric subsidence warming, and increasing tropopause height forced by overshooting updrafts in the eyewall. None of these processes are seen as the direct cause of RI, but rather part of the RI process that includes strong increases in boundary layer moist entropy.
Association of Endocan, Ischemia-Modified Albumin, and hsCRP Levels With Endothelial Dysfunction in Type 2 Diabetes Mellitus
Authors: Balamir Ilhan , Ates Ihsan , Topcuoglu Canan , Turhan Turan
Published: November 2017

We investigated the relationship of ischemia-modified albumin (IMA) and high-sensitivity C-reactive protein (hsCRP) levels with direct (endocan) and indirect (carotid intima–media thickness [cIMT] and 24 hours urine protein excretion) endothelial dysfunction indicators in type 2 diabetes mellitus (T2DM). Patients with T2DM (n = 88) and 88 healthy individuals were included in the study. The median endocan (475.15 vs 216.37 pg/mL; P < .001, respectively) and hsCRP (10.74 vs 3.11 mg/L; P < .001, respectively) and the mean IMA (0.64 ± 0.12 vs 0.51 ± 0.12 absorbance units; P < .001, respectively) levels were higher in participants with endothelial dysfunction compared to those without endothelial dysfunction in T2DM. The 24-hour urine protein excretion and cIMT levels had a positive correlation with hsCRP ( r = .357; P = .001 and r = .592; P < .001, respectively), IMA ( r = .519; P < .001 and r = .495; P < .001, respectively) and endocan ( r = .347; P = .001 and r = .583; P < .001, respectively) levels in the T2DM group. Stepwise multivariable logistic regression analysis, which included laboratory findings found to be associated with endothelial dysfunction, showed that endocan (odds ratio [OR] = 1.456; P = .004), hsCRP (OR = 1.298; P = .008), and IMA (OR = 2.270, P = .003) were independent risk factors. It was found that none of these markers were superior in terms of diagnostic discrimination for endothelial dysfunction. Endocan, IMA, and hsCRP levels were found to be associated with endothelial dysfunction in patients with T2DM.
Can schools meet the promise of continuous improvement?
Authors: Elgart Mark A.
Published: November 2017

Continuous improvement is “an embedded behavior within the culture of a school that constantly focuses on the conditions, processes, and practices that will improve teaching and learning.” The phrase has been part of the lexicon of school improvement for decades, but real progress is rare. Based on its observations of about 5,000 institutions a year, AdvancEd Improvement Network has found that there are strong relationships between effective continuous improvement practices and the following characteristics of high-performing schools: a clear direction, healthy culture, high expectations, impact of instruction, resource management, efficacy of engagement, and implementation capacity.