bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3529: KIM-1 is a novel therapeutic target in renal cell carcinoma
Authors: Sabbisetti Venkata S.
Published: May 2015

Background. Renal cell carcinoma (RCC) is characterized by lack of early warning signs, diverse clinical manifestations, absence of a reliable diagnostic and predictive biomarker, and resistance to targeted therapy. Given the high incidence and worse prognosis, novel approaches for diagnosis, management and treatment of RCC are urgently needed. Kidney Injury Molecule-1 (KIM-1) is not expressed in normal kidney tissues but markedly up-regulated in dedifferentiated proximal tubular epithelial cells following renal injury. We demonstrated KIM-1 is expressed ubiquitoulsy by both primary and metastatic lesions of clear cell and papillary renal cell carcinoma, while barely detectable in other subtypes of RCC. The ectodomain of KIM-1 molecule cleaves by matrix metaloproteinases and sheds into surround milieu. In the present study, we investigated the role of KIM-1 in the pathogenesis of RCC. Methods. KIM-1 is stably transfected in immortalized tubular epithelial cells (LLC-PK1, gain-of-function) and KIM-1 was knockdown in RCC cell lines (loss-of-function) using lentiviral apporach and interoggated KIM-1 function in carcinogenesis. Results. Heterologous expression of KIM-1 increased cell proliferation, induced anchorage indepdent growth, increased migration and invasion potential, and increased the secreation of tumor promoting fractors, including TGF beta and IL-6 in immortalized tubular epithelial cells (PK1-KIM-1); while depletion of KIM-1 in RCC cells leads to cell cycle arrest at G1 phase and senescence. Recently, we and others have demonstrated that KIM-1 is a phosphatildyl serine receptor and the expression of KIM-1 converts a normal epithelial cell into a “semi professional phagocyte” and facilitates the removal of apoptotic and necrotic cells by recognizing phosphotidyl serine (PS) on their cell surface. Our data suggests that during this process, tumor epithelial cells undergo reprogramming and secrete and activate cytokines involved in cell survival and angiogenesis programs. Conclusions. The present study demonstrates that KIM-1-expression promotes tumorigenesis primarily by two distinct mechanisms: i) by directly conferring oncogenic properties to renal epithelial cells; ii) by resulting in production of a variety of chemokines and cytokines that support tumor progression and angiogenesis. We believe that our findings can significantly contribute to the development of novel therapeutic apporaches and in the advancement of management strategies in renal cell carcinoma and help reduce associated mortality and morbidity.

Citation Format: Venkata S. Sabbisetti. KIM-1 is a novel therapeutic target in renal cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3529. doi:10.1158/1538-7445.AM2014-3529
Abstract 3564: A new method for preparation of low-input, PCR-free next generation sequencing libraries
Authors: Kurihara Laurie , Banks L. , Chupreta S. , Couture C. , Kelchner V. , Laliberte J. , Sandhu S. , Spurbeck R. , Makarov V.
Published: May 2015

Sequence analysis of PCR-free Next Generation Sequencing (NGS) libraries demonstrates improved evenness of coverage relative to NGS libraries that have undergone PCR amplification. However, existing PCR-free methods require 1ug or more of input DNA quantity in order to obtain sufficient library yield which restricts such analysis when DNA sample quantity is insufficient. To expand the applicability of PCR-free sequencing, Swift Biosciences has developed a novel adapter attachment chemistry that is more efficient than existing methods. This new technology, Accel-NGS™, results in libraries that capture a higher complexity of each sample which enables a lower input DNA requirement. For Illumina systems, PCR-free Accel-NGS libraries can be prepared from 100ng of input DNA for direct sequencing. PCR-free Accel-NGS libraries demonstrate even coverage across a broad GC content as well as when analyzing whole genome sequence coverage. To enable library preparation from even less DNA, Accel-NGS libraries can also be prepared with a low number of PCR cycles for direct sequencing. The Accel-NGS method with PCR results in more even coverage and less PCR duplicates when compared to existing methods that use PCR. For exome hybridization capture, comparable coverage was achieved for Accel-NGS libraries from 100ng DNA input when compared to an existing method that requires 1ug of DNA input. The Accel-NGS method is fast and automatable; additional advantages when applied to clinical samples are under investigation. PCR-free Accel-NGS libraries can also be prepared for Ion Torrent systems from 5ng of input DNA with comparable sequence quality to existing methods.

Citation Format: Laurie Kurihara, L. Banks, S. Chupreta, C. Couture, V. Kelchner, J.Laliberte, S. Sandhu, R. Spurbeck, V. Makarov. A new method for preparation of low-input, PCR-free next generation sequencing libraries. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3564. doi:10.1158/1538-7445.AM2014-3564
Abstract 3662: Tumor-derived interleukin-1 promotes lymphangiogenesis and lymph node metastasis through activation of M2-type macrophages by lung cancer cells
Authors: Watari Kosuke , Shibata Tomohiro , Kawahara Akihiko , Murakami Yuichi , Nabeshima Hiroshi , Shinoda Ai , Azuma Koichi , Izumi Hiroto , Kage Masayoshi , Kuwano Michihiko , Ono Mayumi
Published: May 2015

Widespread metastases including lymph node have often led to the failure of cancer patient treatments. Lymph node metastasis is closely associated with lymphangiogenesis and poor prognosis in lung cancer. Identifying the molecules involved in these processes could help to advance therapeutic strategies for lung cancer patients. We have asked how cancer cells acquire malignant characteristics including lymph node metastasis and lymphangiogenesis, and also how such highly malignant tumor could be therapeutically overcome. Human malignancies are often initiated and promoted by inflammation, in close association with angiogenesis and lymphangiogenesis, while the recruitment of macrophages and neutrophils to the tumor microenvironment activates cells to support cancer progression. Interleukin (IL-1), a representative inflammatory cytokine, is often expressed in human malignancies including lung cancers with poor prognosis. In this study we examined how IL-1 promotes lymph node metastasis and lymphangiogenesis by lung cancer cell lines expressing higher IL-lα. In our present study, we observed following experimental results.

[1] Tumor growth, lymph node metastasis, lymphangiogenesis and enhanced infiltration of neutrophils and macrophage were all markedly augmented by the highly metastatic cancer cells.

[2] In the highly metastatic tumors, we observed higher expression of IL-1α, IL-1β and CXC chemokines by cancer cells, and also that of VEGF-A and VEGF-C by tumor-associated macrophages, respectively. These tumor-associated macrophages were found to be mainly of the M2 type.

[3] Treatment with an IL-1R antagonist (IL-1Ra) significantly blocked expression of CXC chemokines by cancer cells, and also expression of VEGFs by macrophages when co-cultured with cancer cells in vitro.

[4] Administration of IL-1Ra significantly suppressed tumor growth, lymph node metastasis and lymphangiogenesis, accompanying by significantly decreased infiltration of M2-type macrophage in the highly metastatic tumors.

Together, targeting IL-1/IL-1R signaling pathway and/or M2-type macrophages could be expected to provide useful therapeutic strategy against lymph node metastasis by inflammatory malignant cancer cells.

Citation Format: Kosuke Watari, Tomohiro Shibata, Akihiko Kawahara, Yuichi Murakami, Hiroshi Nabeshima, Ai Shinoda, Koichi Azuma, Hiroto Izumi, Masayoshi Kage, Michihiko Kuwano, Mayumi Ono. Tumor-derived interleukin-1 promotes lymphangiogenesis and lymph node metastasis through activation of M2-type macrophages by lung cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3662. doi:10.1158/1538-7445.AM2014-3662
Abstract 3821: A prognostic model of head and neck cancer ties TP53 mutation to 3p loss
Authors: Gross Andrew M. , Orosco Ryan K. , Shen John P. , Egloff Ann Marie , Carter Hannah , Hoffree Matan , Choueiri Michel , Coffey Charles S. , Lippman Scott M. , Hayes David Neil , Cohen Ezra E. , Grandis Jennifer R. , Nguyen Quyen T. , Ideker Trey
Published: May 2015

Head and neck squamous cell carcinoma (HNSCC) is frequently characterized by aggressive clinical behavior with a propensity for metastasis and recurrence. Current understanding of HNSCC pathogenesis remains limited, and there are few biomarkers that reliably predict patient outcomes such as survival or response to therapy. Here we report a comprehensive analysis of the molecular and clinical features of HNSCC that define patient survival. Building on data and infrastructure established by The Cancer Genome Atlas (TCGA), we develop an approach that integrates molecular events across multiple tiers of ‘omics data to progressively factor patients into subgroups with the greatest survival differences. We show that in HPV negative patients, the detrimental impact of TP53 mutation occurs only in combination with loss of chromosome 3p, leading to a marked decrease in median survival from >5 years for TP53 mutation only to 1.7 years for both events. Conditioned on TP53/3p, patients are stratified by a hierarchy of events incorporating MUC5B mutation, mir-548k expression, and mutation and expression of Abnormal Spindle Protein (ASPM), while in the absence of the TP53/3p event RAS signaling is an important driver. We also show in HPV positive patients that HPV-mediated inactivation of TP53 acts in synergy with 3p deletion. The major findings are replicated in an independent HNSCC cohort as well as a pan-cancer TCGA cohort of over 3000 patients. Together, the identified markers enable a new multi-tiered molecular classification of HNSCC.

Citation Format: Andrew M. Gross, Ryan K. Orosco, John P. Shen, Ann Marie Egloff, Hannah Carter, Matan Hoffree, Michel Choueiri, Charles S. Coffey, Scott M. Lippman, David Neil Hayes, Ezra E. Cohen, Jennifer R. Grandis, Quyen T. Nguyen, Trey Ideker. A prognostic model of head and neck cancer ties TP53 mutation to 3p loss. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3821. doi:10.1158/1538-7445.AM2014-3821
Abstract 3840: Cetuximab-induced testicular toxicity
Authors: Levi Mattan , Popovtzer Aaron , Tzabari Moran , Stemmer Salomon M. , Shalgi Ruth , Ben-Aharon Irit
Published: May 2015

Background:

Cetuximab, an anti-EGFR monoclonal antibody, is the only targeted therapy approved for the treatment of head and neck squamous cell carcinoma (HNSCC) in patients with locally advanced tumors, in association with radiotherapy, and in patients with recurrent or metastatic disease, in association with cisplatin-based chemotherapy. We aimed to study the effect of cetuximab on testicular function and reserve.

Methods:

Male mice were injected intraperitoneally with cetuximab (1mg), or cisplatin (8mg/kg) or the combination of both and sacrificed either 1 week or 6 weeks later. Saline-injected mice served as controls. Testes were excised, weighed and further processed. Glutathione and apoptosis assays were performed on 6 weeks samples for determination of oxidative stress. Immunohistochemistry and confocal microscopy were used to study the effect of cetuximab, cisplatin and their combination on the testis histology as well as on the spermatogonial reserve.

Results:

Cetuximab induced mild apoptosis in the testis. Cisplatin induced enhanced apoptosis and depleted spermatogonial reserve, reflected by reduced DAZL staining (early spermatocyte marker). The combined treatment resulted in further decline in testicular weight compared with cisplatin-only treated mice at 1-month post treatment (p<0.05). Cetuximab enhanced cisplatin-induced oxidative stress, and further depletion of spermatogonial reserve (p<0.05).

Conclusions:

Cetuximab has a mild effect on testicular reserve. Nevertheless, the addition of cetuximab to cisplatin exacerbates cisplatin-induced testicular toxicity.

Citation Format: Mattan Levi, Aaron Popovtzer, Moran Tzabari, Salomon M. Stemmer, Ruth Shalgi, Irit Ben-Aharon. Cetuximab-induced testicular toxicity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3840. doi:10.1158/1538-7445.AM2014-3840
Abstract 3868: Six1 overexpression promotes malignant progression in models of cervical and colon cancer
Authors: Xu Hanwen , Zhang Yu , Pirisi Lucia , Pena Maria Marjorette , Creek Kim E.
Published: May 2015

The overexpression of Six1, a member of the Six family of homeodomain transcription factors, has been found in various human cancers, and is associated with increased tumor progression and metastasis. Previous studies in our laboratory discovered that the expression of Six1 mRNA increased during in vitro progression of human papillomavirus type 16 (HPV16) immortalized human keratinocytes (HKc/HPV16) toward a differentiation-resistant (HKc/DR) phenotype. The overexpression of Six1 induced Epithelial-Mesenchymal Transition (EMT) by the activation of p38 MAPK in HKc/DR. Although immortalized and resistant to serum and calcium-induced differentiation, HKc/DR are not tumorigenic. To further explore the role of Six1 in HPV16 immortalized cells we determined whether overexpression of Six1 in HKc/DR resulted in malignant conversion. We found that HKc/DR overexpressing Six1 (DR-Six1), but not HKc/DR controls (DR-Ctrl), formed squamous cell carcinomas in nude mice. Cancer stem cells are proposed to drive tumor initiation and progression; for this reason we analyzed cancer stem cell markers in DR-Ctrl and DR-Six1. We found that DR-Six1 had an increased CD24-/CD44+ population and increased aldehyde dehydrogenase 1 (ALDH1) expression as compared to DR-Ctrl, indicating a cancer stem cell-like phenotype in Six1 overexpressing cells. We then used the human cervical cancer cell line HeLa to further explore the enhanced tumorigenic and malignant properties associated with Six1 overexpression. We determined that overexpressing Six1 in HeLa increased their ability to form spheroids in vitro and increased tumor size in vivo. As an extension of this work, we investigated the role of Six1 on tumorigenesis and metastasis in colon cancer in vivo and in vitro by using the murine colon cancer cell line MC38. We found that Six1 promoted colon cancer tumorigenesis, progression and metastasis, and increased the population of cancer stem cell-like cells. Taken together, our studies demonstrate that Six1 overexpression increases the cancer stem cell-like cell population, and promotes malignant progression in models of cervical and colon cancer.

Supported by grant P20MD001770 from the National Institute on Minority Health and Health Disparities.

Citation Format: Hanwen Xu, Yu Zhang, Lucia Pirisi, Maria Marjorette Pena, Kim E. Creek. Six1 overexpression promotes malignant progression in models of cervical and colon cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3868. doi:10.1158/1538-7445.AM2014-3868
Abstract 3973: BRICHOS genes CHM1 and ITM2A maintain an undifferentiated, invasive phenotype in Ewing sarcoma
Authors: Heyking Kristina von , Fasan Annette , Burdach Stefan , Richter Günther H.
Published: May 2015

Ewing sarcomas (ES) are highly malignant, osteolytic bone or soft tissue tumors, which are characterized by ews/ets translocations and early metastasis into lung and bone. In this study, we analyzed the role of the BRICHOS domain-containing genes CHM1 and ITM2A in ES pathogenesis, especially in bone-associated tumor growth and metastasis. Both genes are overexpressed in ES and among others appear to be important for chondrogenic differentiation. CHM1 in addition seems directly up-regulated by EWS/FLI1. Using RNA interference, we demonstrate that CHM1 and ITM2A slightly reduced bone invasiveness and osteolysis in vivo that is likely mediated by the suppression of the osteolytic genes HIF1α, IL6, JAG1 and VEGF. Furthermore, CHM1 and ITM2A suppressed the chondrogenic and to a lesser extend the osteogenic differentiation status of ES cells indicating that osteomimicry might play a role in homing, colonizing and invasion into bone tissues. Additionally, we show that both BRICHOS domain-containing genes significantly increased the expression of the stem cell genes, ABCG2 and PROM1. Together with the observed undifferentiated phenotype of ES cells, we demonstrate that CHM1 and ITM2A clearly enhanced lung metastasis in a xenograft mouse model in vivo. Our results suggest that CHM1 and ITM2A are essential players with respect to the undifferentiated phenotype and the metastatic behavior of ES cells.

Citation Format: Kristina von Heyking, Annette Fasan, Stefan Burdach, Günther H. Richter. BRICHOS genes CHM1 and ITM2A maintain an undifferentiated, invasive phenotype in Ewing sarcoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3973. doi:10.1158/1538-7445.AM2014-3973
CARD9 Promotes Sex-Biased Colon Tumors in the APCmin Mouse Model
Authors: Leo Vonny I. , Tan Sze Huey , Bergmann Hanna , Cheah Peh Yean , Chew Min Hoe , Lim Kiat Hon , Ruland Jürgen , Reilly Patrick T.
Published: May 2015

Caspase recuitment domain–containing protein 9 (CARD9) functions in different inflammation pathways to elicit responses to microbial signals and is known to affect intestinal inflammation. Examining the APCmin mouse model of intestinal tumorigenesis and using stringently controlled, sex- and age-matched pairs of CARD9-competent and CARD9-deficient mice, we have found that CARD9 has a restricted but strong effect on tumorigenesis in the large intestine. We have found that CARD9 reduces viability specifically in males and promotes tumorigenesis specifically in the large intestines of these male mice. To our knowledge, this is the first gene ablation in APCmin mice that solely affects colon tumors in male subjects and, as such, may have significant clinical implications. Additional data suggest correlative disruption of plasma cytokine expression and immune infiltration of the tumors. We speculate that known sex-specific differences in human colorectal cancer may involve inflammation, particularly CARD9-dependent inflammation. Cancer Immunol Res; 3(7); 721–6. ©2015 AACR.
MRI Surface-Based Brain Morphometry in Egyptian Autistic and Typically Developing Children
Authors: Saleh Marwa , Nashaat Neveen Hassan , Fahim Cherine , Ibrahim Ahmed Samir , Meguid Nagwa
Published: May 2015

Objectives: The verbal abilities of autistic children differ from those of typically developing ones and they also differ among autistic children themselves. Neuroanatomical changes and an abnormal organization of functional networks are expected to accompany such a neurodevelopmental disorder. The aim of this study was to delineate the brain neuroanatomical changes in Egyptian children with autism and to compare them with previous studies in order to add more insight into the global brain imaging deviations linked to autism. Patients and Methods: Twenty-five autistic children and 25 typically developing children underwent MRI. Further analysis was performed using surface-based morphometry to obtain cortical thickness, brain volume, and cortical complexity. Results: MRI analysis results revealed significantly greater cortical thickness, cortical complexity, and gray matter volume in the autistic as compared to the control group. On the other hand, the white matter volume was significantly smaller. Conclusion: These findings generally align with findings in previous studies, except for occasional differences.
Validation of the Tuebingen CD-25 Inventory as a Measure of Postoperative Health-Related Quality of Life in Patients Treated for Cushing's Disease
Authors: Milian Monika , Kreitschmann-Andermahr Ilonka , Siegel Sonja , Kleist Bernadette , Führer-Sakel Dagmar , Honegger Juergen , Buchfelder Michael , Psaras Tsambika
Published: May 2015

Background: To evaluate the construct and criterion validity of the Tuebingen Cushing's disease quality of life inventory (Tuebingen CD-25) for application in patients treated for Cushing's disease (CD). Methods: A total of 176 patients with adrenocorticotropin hormone-dependent CD (144 of them female, overall mean age 46.1 ± 13.7 years) treated at 3 large tertiary referral centers in Germany were studied. Construct validity was assessed by hypothesis testing (self-perceived symptom reduction assessment) and contrasted groups (patients with vs. without hypercorticolism). For this purpose, already existing data from 55 CD patients was used, representing the hypercortisolemic group. Criterion validity (concurrent validity) was assessed in relation to the Cushing's quality of life questionnaire (CushingQoL), the Short Form 36 health survey (SF-36), and the body mass index (BMI). Results: Patients with self-perceived remarkable symptom reduction had significant lower Tuebingen CD-25 scores (i.e. better health-related quality of life) than patients with self-perceived insufficient symptom reduction (p < 0.05). Similarly, the mean scores of the Tuebingen CD-25 scales were lower in patients without hypercortisolism (total score 27.0 ± 17.2) compared to those with hypercortisolism (total score 45.3 ± 22.1; each p < 0.05), providing evidence for construct validity. Criterion validity was confirmed by the correlations between the Tuebingen CD-25 total score and the CushingQoL (Spearman's coefficient -0.733), as well as all scales of the SF-36 (Spearman's coefficient between -0.447 and -0.700). Conclusion: The analyses presented in this large-sample study provide robust evidence for the construct and criterion validity of the Tuebingen CD-25.
Irene: das sensações às emoções
Authors: Dudzeele Géraldine Cerf de
Published: May 2015

Este artigo relata uma psicoterapia psicanalítica de longo prazo com uma menina autista de 8 anos. O relato do tratamento divide-se em 4 períodos: no primeiro, o tratamento visará à retomada das bases da imagem do corpo de uma menina ainda muito agitada e retraída; no seguinte, há um início de construção do espaço transicional, com a emergência de trocas verbais. Na terceira etapa vê-se o acesso ao espelho e uma melhor comunicação das experiências vividas. E na última verificam-se a consolidação da imagem do corpo bem como o desenvolvimento do jogo e da simbolização.
Da moral nietzschiana ao mal-estar freudiano: algumas aproximações e decorrências éticas
Authors: Viaro Renee Volpato , Valore Luciana Albanese
Published: May 2015

Tomam-se as obras A genealogia da moral, de Nietzsche, e O mal-estar na civilização, de Freud, como leituras modernas acerca do papel desempenhado pelo sentimento de culpa no processo civilizatório. Algumas medidas (discutidas por ambos os autores) tomadas contra o sofrimento advindo da socialização humana são focadas como diagnósticos modernos do processo civilizacional e de seu atual estado, para então, a partir da problemática dos ideais, serem traçadas algumas decorrências éticas (concernentes à psicanálise) diante do conflito entre indivíduo e civilização.
Notas introdutórias sobre os processos psíquicos na infância e adolescência
Authors: Mano Gustavo Caetano de Mattos
Published: May 2015

A prática clínica com crianças e adolescentes segue disparando interrogações que oxigenam a teoria psicanalítica. Nesse sentido, o presente escrito propõe-se a oferecer uma abordagem introdutória acerca da infância e da adolescência à luz das formulações lacanianas sobre o tempo lógico. Fazendo operar as noções de instante de ver, tempo de compreender e momento de concluir, deslocamos a infância e a adolescência do estatuto de etapas do desenvolvimento para tomá-las como processos psíquicos constituintes do sujeito. A partir disso, problematizamos a questão da estruturação, considerando para tal a referência aos significantes-mestres que norteia a psicopatologia psicanalítica.
Ensinar em estabelecimento especializado: relação com a prova e posição subjetiva do professor
Authors: Savournin Florence
Published: May 2015

Esta pesquisa envolve a análise das práticas de ensino com uma dupla referência: à didática e à Psicanálise. O conceito de "relação com a prova" (rapport à l'épreuve) permite explicar o significado atribuído por uma professora especializada à sua experiência com um grupo do Instituto Terapêutico, Educacional e Pedagógico (ITEP) na França. Aplicação didática, sujeito suposto saber, impossível de suportar são as três dimensões que estruturam a relação com a prova nesse espaço-tempo com os alunos, cujo maior desafio é a transmissão do saber. O estudo de caso mostra como, de uma forma sempre singular, um sujeito confronta o seu desejo de transmissão com a prática de ensino.
Fantasia, analogia e narcisismo: Um argumento contra a tradução de “Trieb” por “instinto”
Authors: Silveira Léa
Published: May 2015

O artigo discute uma passagem do texto “O inconsciente” – aquela em que Freud traça uma analogia entre as fantasias e os “instintos dos animais” – apontando-a como algo decisivo para o debate sobre a tradução do termo Trieb. Sua análise resulta na defesa da impossibilidade de vertê-lo por “instinto”, acenando para a impossibilidade correlata de se proceder a uma redução dos principais conceitos freudianos à biologia. Se a atitude de criticar tal redução foi por vezes caracterizada como narcisismo, será necessário constatar que tal denúncia se vale de um conceito concebível apenas quando já se admitiu a distância entre natureza e cultura.
Ser uma pessoa, ser alguém. Os limites do institucionalismo hegeliano
Authors: Colliot-Thélène Catherine
Published: May 2015

É geralmente aceito que a filosofia política de Hegel é institucionalista
no sentido de que ela não se contenta em justificar a necessidade do organismo político, mas que ela expõe suas articulações complexas com esmero de precisão. Enquanto para alguns, como para Axel Honneth, por exemplo, o institucionalismo de Hegel seria excessivo, tenho, inversamente, a tendência de considerar que o interesse de Hegel pelo concreto das instituições é aquilo que constitui a força de sua filosofia política. Parece-me que encontramos nos Princípios da Filosofia do Direito os traços de uma reflexão (discreta) sobre os limites do institucionalizável. São esses traços que eu pretendo identificar, em dois níveis, nesta exposição: aquele do direito abstrato, que será objeto da primeira parte, e aquele da eticidade, ao qual consagrarei a segunda parte da exposição.
Neuromatous Regeneration as a Nerve Response After Catheter-Based Renal Denervation Therapy in a Large Animal Model
Authors: Rousselle Serge D. , Brants Irena K. , Sakaoka Atsushi , Hubbard Brad , Jackson Nicolette D. , Wicks Joan R. , Dillon Krista N. , Naiche L.A. , Hart Randy , Garza Javier A. , Tellez Armando
Published: May 2015

Background—

Renal denervation (RDN) emerged as a therapeutic option for resistant hypertension. Nerve regrowth after RDN has been questioned. We aimed to characterize the nerve response after RDN.

Methods and Results—

Swine underwent bilateral RDN and were followed up for 7, 30, and 90 days and evaluated with S100 (Schwann cell), tyrosine hydroxylase (TH; efferent nerves), and growth-associated protein 43 (neurite regeneration) markers. At 7 days, nerve changes consisted of necrosis associated with perineurial fibrosis and distal atrophy with inflammation. At 30 days changes were substituted by healing changes (ie, fibrosis). This response progressed through 90 days resulting in prominent neuroma formation. Immunohistochemistry at 7 days: TH staining was strongly decreased in treated nerves. Early regenerative attempts were observed with strongly TH and growth-associated protein 43 positive and weak S100 disorganized nerve sprouts within the thickened perineurium. Distal atrophic nerves show weak staining for all 3 markers. At 30 days, affected nerves show a weak TH and S100 staining. Evident growth-associated protein 43+ disorganized neuromatous tangles in the thickened perineurium of severed nerves were observed. At 90 days, some TH expression was observed together with prominent S100+ and growth-associated protein 43+ neuromatous tangles with disorganized architecture. The potential for regenerative activity is unlikely based on the disrupted architecture of these neuromatous tangles at the radiofrequency lesion sites.

Conclusions—

This study is the first documentation that a progressive regenerative response occurs as early as 7 days after RDN, resulting in a poorly organized neuromatous regeneration. This finding is of paramount importance to further establish the potential functional significance of a regeneration after RDN.
Efficient Gene Disruption in Cultured Primary Human Endothelial Cells by CRISPR/Cas9
Authors: Abrahimi Parwiz , Chang William G. , Kluger Martin S. , Qyang Yibing , Tellides George , Saltzman W. Mark , Pober Jordan S.
Published: May 2015

Rationale:

The participation of endothelial cells (EC) in many physiological and pathological processes is widely modeled using human EC cultures, but genetic manipulation of these untransformed cells has been technically challenging. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 nuclease (Cas9) technology offers a promising new approach. However, mutagenized cultured cells require cloning to yield homogeneous populations, and the limited replicative lifespan of well-differentiated human EC presents a barrier for doing so.

Objective:

To create a simple but highly efficient method using CRISPR/Cas9 to generate biallelic gene disruption in untransformed human EC.

Methods and Results:

To demonstrate proof-of-principle, we used CRISPR/Cas9 to disrupt the gene for the class II transactivator. We used endothelial colony forming cell–derived EC and lentiviral vectors to deliver CRISPR/Cas9 elements to ablate EC expression of class II major histocompatibility complex molecules and with it, the capacity to activate allogeneic CD4
+
T cells. We show the observed loss-of-function arises from biallelic gene disruption in class II transactivator that leaves other essential properties of the cells intact, including self-assembly into blood vessels in vivo, and that the altered phenotype can be rescued by reintroduction of class II transactivator expression.

Conclusions:

CRISPR/Cas9-modified human EC provides a powerful platform for vascular research and for regenerative medicine/tissue engineering.
Longitudinal Blood Pressure Control, Long-Term Mortality, and Predictive Utility of Serum Liver Enzymes and Bilirubin in Hypertensive Patients
Authors: McCallum Linsay , Panniyammakal Jeemon , Hastie Claire E. , Hewitt Jonathan , Patel Rajan , Jones Gregory C. , Muir Scott , Walters Matthew , Sattar Naveed , Dominiczak Anna F. , Padmanabhan Sandosh
Published: May 2015

There is accruing evidence from general population studies that serum bilirubin and liver enzymes affect blood pressure (BP) and cardiovascular risk, but it is unclear whether these have an impact on hypertensive patients in terms of long-term survival or BP control. We analyzed 12 000 treated hypertensive individuals attending a tertiary care clinic followed up for 35 years for association between baseline liver function tests and cause-specific mortality after adjustment for conventional cardiovascular covariates. Generalized estimating equations were used to study the association of liver tests and follow-up BP. The total time at risk was 173 806 person years with median survival 32.3 years. Follow-up systolic BP over 5 years changed by −0.4 (alanine transaminase and bilirubin), +2.1(alkaline phosphatase), +0.9(γ-glutamyl transpeptidase) mm Hg for each standard deviation increase. Serum total bilirubin and alanine transaminase showed a significant negative association with all-cause and cardiovascular mortality, whereas alkaline phosphatase and γ-glutamyl transpeptidase showed a positive association and aspartate transaminase showed a U-shapedassociation. Serum bilirubin showed an incremental improvement of continuous net reclassification improvement by 8% to 26% for 25 year and 35 year cardiovascular mortality, whereas all liver markers together improved continuous net reclassification improvement by 19% to 47% compared with reference model. In hypertensive patients, serum liver enzymes and bilirubin within 4 standard deviations of the mean show independent effects on mortality and BP control. Our findings would support further studies to elucidate the mechanisms by which liver enzymes and bilirubin may exert an effect on BP and cardiovascular risk, but there is little support for using them in risk stratification.
Determinants of Aortic Root Dilatation and Reference Values Among Young Adults Over a 20-Year Period
Authors: Teixido-Tura Gisela , Almeida Andre L.C. , Choi Eui-Young , Gjesdal Ola , Jacobs David R. , Dietz Harry C. , Liu Kiang , Sidney Stephen , Lewis Cora E. , Garcia-Dorado David , Evangelista Artur , Gidding Samuel , Lima João A.C.
Published: May 2015

Aortic size increases with age, but factors related to such dilatation in healthy young adult population have not been studied. We aim to evaluate changes in aortic dimensions and its principal correlates among young adults over a 20-year time period. Reference values for aortic dimensions in young adults by echocardiography are also provided. Healthy Coronary Artery Risk Development in Young Adults (CARDIA) study participants aged 23 to 35 years in 1990–1991 (n=3051) were included after excluding 18 individuals with significant valvular dysfunction. Aortic root diameter (ARD) by M-mode echocardiography at year-5 (43.7% men; age, 30.2±3.6 years) and year-25 CARDIA exams was obtained. Univariable and multivariable analyses were performed to assess associations of ARD with clinical data at years-5 and -25. ARD from year-5 was used to establish reference values of ARD in healthy young adults. ARD at year-25 was greater in men (33.3±3.7 versus 28.7±3.4 mm;
P
<0.001) and in whites (30.9±4.3 versus 30.5±4.1 mm;
P
=0.006). On multivariable analysis, ARD at year-25 was positively correlated with male sex, white ethnicity, age, height, weight, 20-year gain in weight, active smoking at baseline, and 20-year increase in diastolic, systolic, and mean arterial pressure. A figure showing the estimated 95th percentile of ARD by age and body surface area stratified by race and sex is provided. This study demonstrates that smoking, blood pressure, and increase in body weight are the main modifiable correlates of aortic root dilation during young adulthood. Our study also provides reference values for ARD in young adults.
Activation of the Neuroprotective Angiotensin-Converting Enzyme 2 in Rat Ischemic Stroke
Authors: Bennion Douglas M. , Haltigan Emily A. , Irwin Alexander J. , Donnangelo Lauren L. , Regenhardt Robert W. , Pioquinto David J. , Purich Daniel L. , Sumners Colin
Published: May 2015

The angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas axis represents a promising target for inducing stroke neuroprotection. Here, we explored stroke-induced changes in expression and activity of endogenous angiotensin-converting enzyme 2 and other system components in Sprague–Dawley rats. To evaluate the clinical feasibility of treatments that target this axis and that may act in synergy with stroke-induced changes, we also tested the neuroprotective effects of diminazene aceturate, an angiotensin-converting enzyme 2 activator, administered systemically post stroke. Among rats that underwent experimental endothelin-1–induced ischemic stroke, angiotensin-converting enzyme 2 activity in the cerebral cortex and striatum increased in the 24 hours after stroke. Serum angiotensin-converting enzyme 2 activity was decreased within 4 hours post stroke, but rebounded to reach higher than baseline levels 3 days post stroke. Treatment after stroke with systemically applied diminazene resulted in decreased infarct volume and improved neurological function without apparent increases in cerebral blood flow. Central infusion of A-779, a Mas receptor antagonist, resulted in larger infarct volumes in diminazene-treated rats, and central infusion of the angiotensin-converting enzyme 2 inhibitor MLN-4760 alone worsened neurological function. The dynamic alterations of the protective angiotensin-converting enzyme 2 pathway after stroke suggest that it may be a favorable therapeutic target. Indeed, significant neuroprotection resulted from poststroke angiotensin-converting enzyme 2 activation, likely via Mas signaling in a blood flow–independent manner. Our findings suggest that stroke therapeutics that target the angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas axis may interact cooperatively with endogenous stroke-induced changes, lending promise to their further study as neuroprotective agents.
Reexamining the Effect of Antihypertensive Medications on Falls in Old Age
Authors: Lipsitz Lewis A. , Habtemariam Daniel , Gagnon Margaret , Iloputaife Ikechukwu , Sorond Farzaneh , Tchalla Achille E. , Dantoine Thierry F. , Travison Thomas G.
Published: May 2015

Conflicting data on the relationship between antihypertensive medications and falls in elderly people may lead to inappropriate undertreatment of hypertension in an effort to prevent falls. We aimed to clarify the relationships between the chronic use of different classes of antihypertensive medications and different types of falls, to determine the effect of medication dose, and to assess whether the risk of falls is associated with differences in cerebral blood flow. We assessed demographics, clinical characteristics, and chronic antihypertensive medication use in 598 community-dwelling people with hypertension, aged 70 to 97 years, then followed them prospectively for self-reported falls using monthly calendar postcards and telephone interviews. Antihypertensive medication use was not associated with an increased risk of falls. Participants reporting use of angiotensin-converting enzyme inhibitors had a significantly decreased 1-year risk of injurious falls (odds ratio, 0.62; 95% confidence interval, 0.39–0.96), whereas those using calcium channel blockers had a decreased risk of all falls (odds ratio, 0.62; 95% confidence interval, 0.42–0.91) and indoor falls (odds ratio, 0.57; 95% confidence interval, 0.36–0.91), compared with participants not taking these drugs. Larger doses of these classes were associated with a lower fall risk. Participants taking calcium channel blockers had higher cerebral blood flow than those not taking these medications. In relatively healthy community-dwelling elderly people, high doses of antihypertensive agents are not associated with an increased risk of falls.
Stable Task Representations under Attentional Load Revealed with Multivariate Pattern Analysis of Human Brain Activity
Authors: Chan Jason L. , Kucyi Aaron , DeSouza Joseph F. X.
Published: May 2015

Performing multiple tasks concurrently places a load on limited attentional resources and results in disrupted task performance. Although human neuroimaging studies have investigated the neural correlates of attentional load, how attentional load affects task processing is poorly understood. Here, task-related neural activity was investigated using fMRI with conventional univariate analysis and multivariate pattern analysis (MVPA) while participants performed blocks of prosaccades and antisaccades, either with or without a rapid serial visual presentation (RSVP) task. Performing prosaccades and antisaccades with RSVP increased error rates and RTs, decreased mean activation in frontoparietal brain areas associated with oculomotor control, and eliminated differences in activation between prosaccades and antisaccades. However, task identity could be decoded from spatial patterns of activation both in the absence and presence of an attentional load. Furthermore, in the FEFs and intraparietal sulcus, these spatial representations were found to be similar using cross-trial-type MVPA, which suggests stability under attentional load. These results demonstrate that attentional load may disrupt the strength of task-related neural activity, rather than the identity of task representations.
Increased Stimulus Expectancy Triggers Low-frequency Phase Reset during Restricted Vigilance
Authors: ten Oever Sanne , van Atteveldt Nienke , Sack Alexander T.
Published: May 2015

Temporal cues can be used to selectively attend to relevant information during abundant sensory stimulation. However, such cues differ vastly in the accuracy of their temporal estimates, ranging from very predictable to very unpredictable. When cues are strongly predictable, attention may facilitate selective processing by aligning relevant incoming information to high neuronal excitability phases of ongoing low-frequency oscillations. However, top–down effects on ongoing oscillations when temporal cues have some predictability, but also contain temporal uncertainties, are unknown. Here, we experimentally created such a situation of mixed predictability and uncertainty: A target could occur within a limited time window after cue but was always unpredictable in exact timing. Crucially to assess top–down effects in such a mixed situation, we manipulated target probability. High target likelihood, compared with low likelihood, enhanced delta oscillations more strongly as measured by evoked power and intertrial coherence. Moreover, delta phase modulated detection rates for probable targets. The delta frequency range corresponds with half-a-period to the target occurrence window and therefore suggests that low-frequency phase reset is engaged to produce a long window of high excitability when event timing is uncertain within a restricted temporal window.
Taxonomy and biology of a new ambrosia gall midge Daphnephila urnicola sp. nov. (Diptera: Cecidomyiidae) inducing urn-shaped leaf galls on two species of Machilus (Lauraceae) in Taiwan
Authors: PAN LIANG-YU , CHIANG TUNG-CHUAN , WENG YU-CHU , CHEN WEN-NENG , HSIAO SHU-CHUAN , TOKUDA MAKOTO , TSAI CHENG-LUNG , YANG MAN-MIAO
Published: May 2015

Recent field surveys show that galls induced by Daphnephila spp. (Cecidomyiidae) on Machilus spp. (Lauraceae) are common in Taiwan, yet only five species, four leaf-gall inducers and one stem-gall inducer on M. thunbergii, have been named in the past. Here we describe a new species, Daphnephila urnicola sp. nov. Chiang, Yang & Tokuda, inducing urn-shaped galls on leaves of both M. zuihoensis and M. mushaensis. Comparisons of D. urnicola populations on M. zuihoensis and on M. mushaensis, indicate that they belong to one species, a result supported by gall midge morphology, life-history traits, gall shape and structure, the developmental process of gall tissues, fungal associations, and DNA-sequencing data. Size and structure of the gall operculum was found to differ between M. zuihoensis and M. mushahaensis.
Moisture Sources of Torrential Rainfall Events in the Sichuan Basin of China during Summers of 2009–13
Authors: Huang Yongjie , Cui Xiaopeng
Published: May 2015

Water vapor sources and transport paths associated with torrential rains are very important to research and forecasts. This study investigates the main moisture sources and transport paths related to torrential rainfall events in the Sichuan basin of China, which is located east of the Tibetan Plateau, using a Lagrangian flexible particle dispersion model (FLEXPART). Based on the analysis of the torrential rainfall distribution during 2009–13, four study areas are selected in the basin. Particles that have a great contribution to the torrential rainfall events within the four study areas are traced back for 10 days, and a quantitative analysis of the contributions from various moisture sources to the torrential rainfall events is also conducted. The results indicate that a large number of target particles start at the Arabian Sea and the Bay of Bengal, land on the Indo-China Peninsula, and finally reach the study areas. This is an important moisture transport path for the torrential rainfall events within the four study areas. Another important path is from the neighborhood of the Sichuan basin. The total moisture supplies from all examined moisture sources within the whole atmospheric layer account for more than 90% of precipitation within the study areas. There are two major moisture sources, the Sichuan basin and the Bay of Bengal, and the South China Sea could be another important moisture source region for the torrential rains in the northeastern Sichuan basin.
Improvement of Statistical Postprocessing Using GEFS Reforecast Information
Authors: Guan Hong , Cui Bo , Zhu Yuejian
Published: May 2015

The National Oceanic and Atmospheric Administration/Earth System Research Laboratory (NOAA/ESRL) generated a multidecadal (from 1985 to present) ensemble reforecast database for the 2012 version of the Global Ensemble Forecast System (GEFS). This dataset includes 11-member reforecasts initialized once per day at 0000 UTC. This GEFS version has a strong cold bias for winter and warm bias for summer in the Northern Hemisphere. Although the operational decaying average bias-correction approach performs well in winter and summer, it sometimes fails during the spring and fall transition seasons at long lead times (>~5 days). In this paper, 24- (1985–2008) and 25-yr (1985–2009) reforecast biases are used to calibrate 2-m temperature forecasts in 2009 and 2010, respectively. The reforecast-calibrated forecasts for both years are more accurate than those adjusted by the decaying average method during transition seasons. A long training period (>5 yr) is necessary to help avoid a large impact on bias correction from an extreme year case and keep a broader diversity of weather scenarios. The improvement from using the full 25-yr, 31-day window, weekly training dataset is almost equivalent to that from using daily training samples. This provides an option to reduce computational expenses while maintaining a desired accuracy. To provide the potential to improve forecast accuracy for transition seasons, reforecast information is added into the current operational bias-correction method. The relative contribution of the two methods is determined by the correlation between the ensemble mean and analysis. This method improves the forecast accuracy for most of the year with a maximum benefit during April–June.