bluuebunny/crossref_metadata_2025 huggingface dataset:
(Pro)renin receptor regulates lung development via the Wnt/β-catenin signaling pathway
Authors: Liu Jie , Zhou Yafan , Liu Yalan , Li Lei , Chen Yan , Liu Yali , Feng Yumei , Yosypiv Ihor V. , Song Renfang , Peng Hua
Published: May 2019

The (pro)renin receptor [(P)RR] binds to prorenin to activate the renin-angiotensin system and is essential for the development of many different organ systems. Whether the (P)RR also plays a role in lung development is unknown. Immunostaining was used to determine the spatial-temporal distribution of (P)RR in the embryonic, postnatal, and adult lungs. We created a lung-specific (P)RR knockout mouse [ Foxd1cre/+ -(P)RRflox/flox] and assessed changes in lung morphology, cell proliferation, and apoptosis using immunohistochemistry and TUNEL staining. (P)RR function was confirmed by using siRNA to knock down (P)RR in human bronchial epithelial cells (HBECs) and then using the CCK-8 assay and flow cytometry to assess cell proliferation and apoptosis. Gene expression changes after knockdown were assessed by RT-PCR and Western blotting. (P)RR is expressed in the club cells of the bronchial epithelium, and expression increases throughout development. Lung-specific (P)RR knockout disrupted branching morphogenesis, leading to lung hypoplasia and neonatal mortality. These defects were associated with increased apoptosis and decreased proliferation of the pulmonary epithelial and mesenchymal cells and may be mediated by downregulation of Wnt11, β-catenin, and Axin2. (P)RR regulates lung development through canonical Wnt/β-catenin signaling and may present a new target for strategies to treat lung hypoplasia.
Early podocyte injury and elevated levels of urinary podocyte-derived extracellular vesicles in swine with metabolic syndrome: role of podocyte mitochondria
Authors: Zhang Li-Hong , Zhu Xiang-Yang , Eirin Alfonso , Nargesi Arash Aghajani , Woollard John R. , Santelli Adrian , Sun In O. , Textor Stephen C. , Lerman Lilach O.
Published: May 2019

Metabolic syndrome (MetS) is associated with nutrient surplus and kidney hyperfiltration, accelerating chronic renal failure. The potential involvement of podocyte damage in early MetS remains unclear. Mitochondrial dysfunction is an important determinant of renal damage, but whether it contributes to MetS-related podocyte injury remains unknown. Domestic pigs were studied after 16 wk of diet-induced MetS, MetS treated with the mitochondria-targeted peptide elamipretide (ELAM; 0.1 mg·kg−1·day−1 sc) for the last month of diet, and lean controls ( n = 6 pigs/group). Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured using multidetector computed tomography, and podocyte and mitochondrial injury were measured by light and electron microscopy. Urinary levels of podocyte-derived extracellular vesicles (pEVs; nephrin positive/podocalyxin positive) were characterized by flow cytometry. Body weight, blood pressure, RBF, and GFR were elevated in MetS. Glomerular size and glomerular injury score were also elevated in MetS and decreased after ELAM treatment. Evidence of podocyte injury, impaired podocyte mitochondria, and foot process width were all increased in MetS but restored with ELAM. The urinary concentration of pEVs was elevated in MetS pigs and directly correlated with renal dysfunction, glomerular injury, and fibrosis and inversely correlated with glomerular nephrin expression. Additionally, pEV numbers were elevated in the urine of obese compared with lean human patients. Early MetS induces podocyte injury and mitochondrial damage, which can be blunted by mitoprotection. Urinary pEVs reflecting podocyte injury might represent early markers of MetS-related kidney disease and a novel therapeutic target.
Characterizing novel olfactory receptors expressed in the murine renal cortex
Authors: Halperin Kuhns Victoria L. , Sanchez Jason , Sarver Dylan C. , Khalil Zoya , Rajkumar Premraj , Marr Kieren A. , Pluznick Jennifer L.
Published: May 2019

The kidney uses specialized G protein-coupled receptors, including olfactory receptors (ORs), to act as sensors of molecules and metabolites. In the present study, we cloned and studied seven renal ORs, which we previously found to be expressed in the murine renal cortex. As most ORs are orphan receptors, our goal was to identify ligands for these ORs in the hope that this will guide future research into their functional roles. We identified novel ligands for two ORs: Olfr558 and Olfr90. For Olfr558, we confirmed activation by previously reported ligands and identified 16 additional carboxylic acids that activated this OR. The strongest activation of Olfr558 was produced by butyric, cyclobutanecarboxylic, isovaleric, 2-methylvaleric, 3-methylvaleric, 4-methylvaleric, and valeric acids. The primary in vivo source of both butyric and isovaleric acids is gut microbial metabolism. We also identified 14 novel ligands that activated Olfr90, the strongest of which were 2-methyl-4-propyl-1,3-oxathiane, 1-octen-3-ol, 2-octanol, and 3-octanol. Interestingly, 8 of these 14 ligands are of fungal origin. We also investigated the tissue distribution of these receptors and found that they are each found in a subset of “nonsensory” tissues. Finally, we examined the putative human orthologs of Olfr558 and Olfr90 and found that the human ortholog of Olfr558 (OR51E1) has a similar ligand profile, indicating that the role of this OR is likely evolutionarily conserved. In summary, we examined seven novel renal ORs and identified new ligands for Olfr558 and Olfr90, which imply that both of these receptors serve to detect metabolites produced by microorganisms.
Response to coincident inputs in electrically coupled primary afferents is heterogeneous and is enhanced by H-current (IH) modulation
Authors: Davoine Federico , Curti Sebastian
Published: May 2019

Electrical synapses represent a widespread modality of interneuronal communication in the mammalian brain. These contacts, by lowering the effectiveness of random or temporally uncorrelated inputs, endow circuits of coupled neurons with the ability to selectively respond to simultaneous depolarizations. This mechanism may support coincidence detection, a property involved in sensory perception, organization of motor outputs, and improvement signal-to-noise ratio. While the role of electrical coupling is well established, little is known about the contribution of the cellular excitability and its modulations to the susceptibility of groups of neurons to coincident inputs. Here, we obtained dual whole cell patch-clamp recordings of pairs of mesencephalic trigeminal (MesV) neurons in brainstem slices from rats to evaluate coincidence detection and its determinants. MesV neurons are primary afferents involved in the organization of orofacial behaviors whose cell bodies are electrically coupled mainly in pairs through soma-somatic gap junctions. We found that coincidence detection is highly heterogeneous across the population of coupled neurons. Furthermore, combined electrophysiological and modeling approaches reveal that this heterogeneity arises from the diversity of MesV neuron intrinsic excitability. Consistently, increasing these cells’ excitability by upregulating the hyperpolarization-activated cationic current ( IH) triggered by cGMP results in a dramatic enhancement of the susceptibility of coupled neurons to coincident inputs. In conclusion, the ability of coupled neurons to detect coincident inputs is critically shaped by their intrinsic electrophysiological properties, emphasizing the relevance of neuronal excitability for the many functional operations supported by electrical transmission in mammals.

NEW & NOTEWORTHY We show that the susceptibility of pairs of coupled mesencephalic trigeminal (MesV) neurons to coincident inputs is highly heterogenous and depends on the interaction between electrical coupling and neuronal excitability. Additionally, upregulating the hyperpolarization-activated cationic current ( IH) by cGMP results in a dramatic increase of this susceptibility. The IHand electrical synapses have been shown to coexist in many neuronal populations, suggesting that modulation of this conductance could represent a common strategy to regulate circuit operation supported by electrical coupling.
A review of mechanical and synaptic processes in otolith transduction of sound and vibration for clinical VEMP testing
Authors: Curthoys Ian S. , Grant J. Wally , Pastras Christopher J. , Brown Daniel J. , Burgess Ann M. , Brichta Alan M. , Lim Rebecca
Published: May 2019

Older studies of mammalian otolith physiology have focused mainly on sustained responses to low-frequency (<50 Hz) or maintained linear acceleration. So the otoliths have been regarded as accelerometers. Thus evidence of otolithic activation and high-precision phase locking to high-frequency sound and vibration appears to be very unusual. However, those results are exactly in accord with a substantial body of knowledge of otolith function in fish and frogs. It is likely that phase locking of otolith afferents to vibration is a general property of all vertebrates. This review examines the literature about the activation and phase locking of single otolithic neurons to air-conducted sound and bone-conducted vibration, in particular the high precision of phase locking shown by mammalian irregular afferents that synapse on striolar type I hair cells by calyx endings. Potassium in the synaptic cleft between the type I hair cell receptor and the calyx afferent ending may be responsible for the tight phase locking of these afferents even at very high discharge rates. Since frogs and fish do not possess full calyx endings, it is unlikely that they show phase locking with such high precision and to such high frequencies as has been found in mammals. The high-frequency responses have been modeled as the otoliths operating in a seismometer mode rather than an accelerometer mode. These high-frequency otolithic responses constitute the neural basis for clinical vestibular-evoked myogenic potential tests of otolith function.
Slow oscillatory changes of DPOAE magnitude and phase after exposure to intense low-frequency sounds
Authors: Ueberfuhr Margarete A. , Drexl Markus
Published: May 2019

Sensitive sound detection within the mammalian cochlea is performed by hair cells surrounded by cochlear fluids. Maintenance of cochlear fluid homeostasis and tight regulation of intracellular conditions in hair cells are crucial for the auditory transduction process but can be impaired by intense sound stimulation. After a short, intense low-frequency sound, the cochlea shows the previously described “bounce phenomenon,” which manifests itself as slow oscillatory changes of hearing thresholds and otoacoustic emissions. In this study, distortion product otoacoustic emissions (DPOAEs) were recorded after Mongolian gerbils were exposed to intense low-frequency sounds (200 Hz, 100 dB SPL) with different exposure times up to 1 h. After all sound exposure durations, a certain percentage of recordings (up to 80% after 1.5-min-long exposure) showed oscillatory DPOAE changes, similar to the bounce phenomenon in humans. Changes were quite uniform with respect to size and time course, and they were independent from sound exposure duration. Changes showed states of hypo- and hyperactivity with either state preceding the other. The direction of changes was suggested to depend on the static position of the cochlear operating point. As assessed with DPOAEs, no indication for a permanent damage after several or long exposure times was detected. We propose that sensitivity changes occur due to alterations of the mechanoelectrical transduction process of outer hair cells. Those alterations could be induced by different challenged homeostatic processes with slow electromotility of outer hair cells being the most plausible source of the bounce phenomenon.

NEW & NOTEWORTHY Low-frequency, high-intensity sound can cause slowly cycling activity changes in the mammalian cochlea. We examined the effect of low-frequency sound duration on the degree of these alterations. We found that cochlear changes showed a stereotypical biphasic pattern independent of sound exposure duration, but the probability that significant changes occurred decreased with increasing sound duration. Despite exposure durations of up to 1 h, no permanent or transient impairments of the cochlea were detected.
Inflammatory Breast Cancer Promotes Development of M2 Tumor-Associated Macrophages and Cancer Mesenchymal Cells through a Complex Chemokine Network
Authors: Valeta-Magara Amanda , Gadi Abhilash , Volta Viviana , Walters Beth , Arju Rezina , Giashuddin Shah , Zhong Hua , Schneider Robert J.
Published: May 2019

Inflammatory breast cancer (IBC) is a highly aggressive form of breast cancer that displays profound cancer stem cell (CSC) and mesenchymal features that promote rapid metastasis. Another hallmark of IBC is high infiltration of M2 tumor-associated (immune-suppressing) macrophages. The molecular mechanism that drives these IBC phenotypes is not well understood. Using patient breast tumor specimens, breast cancer cell lines, and a patient-derived xenograft model of IBC, we demonstrate that IBC strongly expresses IL8 and growth-regulated oncogene (GRO) chemokines that activate STAT3, which promotes development of high levels of CSC-like cells and a mesenchymal phenotype. We also show that IBC expresses high levels of many monocyte recruitment and macrophage polarization factors that attract and differentiate monocytes into tumor-promoting, immune-suppressing M2-like macrophages. The M2 macrophages in turn were found to secrete high levels of IL8 and GRO chemokines, thereby creating a feed-forward chemokine loop that further drives an IBC epithelial-to-mesenchymal transition. Our study uncovers an intricate IBC-initiated autocrine–paracrine signaling network between IBC cells and monocytes that facilitates development of this highly aggressive form of breast cancer.

Significance:

This study uncovers a signaling network in which IBC cells commandeer macrophages to become tumor-promoting, and they in turn drive IBC cells to be more cancer stem-like, mesenchymal, and aggressive.
Stromal Support of Metabolic Function through Mitochondrial Transfer in Multiple Myeloma
Authors: Boise Lawrence H. , Shanmugam Mala
Published: May 2019

Marlein and colleagues demonstrate in multiple myeloma, bone marrow stromal cells transfer mitochondria to myeloma cells to increase cellular respiration, resulting in increased proliferation. The intercellular transfer occurs through the formation of tunneling nanotubes that connect the myeloma cell to the stromal cell and is dependent on surface CD38 expression on myeloma cells. CD38 is an important therapeutic target in myeloma, therefore, regulation of myeloma metabolism may play a role in the activity of this therapeutic approach. The study reinforces the importance of intercellular interactions in the tumor microenvironment and sheds new light on the control of metabolism in myeloma.

See related article by Marlein et al., p. 2285
TFE3 Xp11.2 Translocation Renal Cell Carcinoma Mouse Model Reveals Novel Therapeutic Targets and Identifies GPNMB as a Diagnostic Marker for Human Disease
Authors: Baba Masaya , Furuya Mitsuko , Motoshima Takanobu , Lang Martin , Funasaki Shintaro , Ma Wenjuan , Sun Hong-Wei , Hasumi Hisashi , Huang Ying , Kato Ikuma , Kadomatsu Tsuyoshi , Satou Yorifumi , Morris Nicole , Karim Baktiar O. , Ileva Lilia , Kalen Joseph D. , Wilan Krisna Luh Ade , Hasumi Yukiko , Sugiyama Aiko , Kurahashi Ryoma , Nishimoto Koshiro , Oyama Masafumi , Nagashima Yoji , Kuroda Naoto , Araki Kimi , Eto Masatoshi , Yao Masahiro , Kamba Tomomi , Suda Toshio , Oike Yuichi , Schmidt Laura S. , Linehan W. Marston
Published: May 2019

Renal cell carcinoma (RCC) associated with Xp11.2 translocation (TFE3-RCC) has been recently defined as a distinct subset of RCC classified by characteristic morphology and clinical presentation. The Xp11 translocations involve the TFE3 transcription factor and produce chimeric TFE3 proteins retaining the basic helix–loop–helix leucine zipper structure for dimerization and DNA binding suggesting that chimeric TFE3 proteins function as oncogenic transcription factors. Diagnostic biomarkers and effective forms of therapy for advanced cases of TFE3-RCC are as yet unavailable. To facilitate the development of molecular based diagnostic tools and targeted therapies for this aggressive kidney cancer, we generated a translocation RCC mouse model, in which the PRCC-TFE3 transgene is expressed specifically in kidneys leading to the development of RCC with characteristic histology. Expression of the receptor tyrosine kinase Ret was elevated in the kidneys of the TFE3-RCC mice, and treatment with RET inhibitor, vandetanib, significantly suppressed RCC growth. Moreover, we found that Gpnmb (Glycoprotein nonmetastatic B) expression was notably elevated in the TFE3-RCC mouse kidneys as seen in human TFE3-RCC tumors, and confirmed that GPNMB is the direct transcriptional target of TFE3 fusions. While GPNMB IHC staining was positive in 9/9 cases of TFE3-RCC, Cathepsin K, a conventional marker for TFE3-RCC, was positive in only 67% of cases. These data support RET as a potential target and GPNMB as a diagnostic marker for TFE3-RCC. The TFE3-RCC mouse provides a preclinical in vivo model for the development of new biomarkers and targeted therapeutics for patients affected with this aggressive form of RCC.

Implications:

Key findings from studies with this preclinical mouse model of TFE3-RCC underscore the potential for RET as a therapeutic target for treatment of patients with TFE3-RCC, and suggest that GPNMB may serve as diagnostic biomarker for TFE3 fusion RCC.
Evaluation of Tumor Cell–Tumor Microenvironment Component Interactions as Potential Predictors of Patient Response to Napabucasin
Authors: Chang An-Yun , Hsu Eric , Patel Jaimin , Li Yiqun , Zhang Minjie , Iguchi Haruhisa , Rogoff Harry A.
Published: May 2019

Napabucasin is an NAD(P)H:quinone oxidoreductase 1 (NQO1)-bioactivatable small molecule hypothesized to affect multiple oncogenic pathways. In a prespecified, retrospective analysis of the napabucasin phase III CO.23 study, overall survival was longer for napabucasin versus placebo in patients expressing phosphorylated STAT3 (pSTAT3) in tumor cells and cells of the tumor microenvironment (TME). We hypothesized that a connection may exist between NQO1 expression in cancer cells and pSTAT3 in tumor cells and the TME. In 3D spheroid cocultures of cancer cells and cancer-associated fibroblasts, the antitumor activity of napabucasin was NQO1 dependent. The levels of cytokines such as IL6, CXCL10, and GM-CSF were higher in NQO1-positive versus NQO1-deleted cocultures. These differentially secreted cytokines promoted STAT3 phosphorylation in tumor cells and the TME. NQO1-expressing, napabucasin-sensitive tumor cells can modify tumor cells and the TME to promote STAT3 phosphorylation, suggesting that pSTAT3 may be used to identify a subpopulation of patients who would likely respond to napabucasin.

Implications:

pSTAT3 is a potential biomarker for patient response to the anticancer drug napabucasin.

Visual Overview: http://mcr.aacrjournals.org/content/molcanres/17/7/1429/F1.large.jpg.
Paracrine Interaction of Cancer Stem Cell Populations Is Regulated by the Senescence-Associated Secretory Phenotype (SASP)
Authors: Lagunas Angelica M. , Francis Marybeth , Maniar Nisha B. , Nikolova Gergana , Wu Jianchun , Crowe David L.
Published: May 2019

Dyskeratosis congenita is a telomere DNA damage syndrome characterized by defective telomere maintenance, bone marrow failure, and increased head and neck cancer risk. The Pot1b−/−;Terc+/− mouse exhibits some features of dyskeratosis congenita, but head and neck cancer was not reported in this model. To model the head and neck cancer phenotype, we created unique Pot1b- and p53-null–mutant models which allow genetic lineage tracing of two distinct stem cell populations. Loss of Pot1b expression depleted stem cells via ATR/Chk1/p53 signaling. Tumorigenesis was inhibited in Pot1b−/−;p53+/+ mice due to cellular senescence. Pot1b−/−;p53−/− tumors also exhibited senescence, but proliferated and metastasized with expansion of Lgr6+ stem cells indicative of senescence-associated secretory phenotype. Selective depletion of the small K15+ stem cell fraction resulted in reduction of Lgr6+ cells and inhibition of tumorigenesis via senescence. Gene expression studies revealed that K15+ cancer stem cells regulate Lgr6+ cancer stem cell expansion via chemokine signaling. Genetic ablation of the chemokine receptor Cxcr2 inhibited cancer stem cell expansion and tumorigenesis via senescence. The effects of chemokines were primarily mediated by PI3K signaling, which is a therapeutic target in head and neck cancer.

Implications:

Paracrine interactions of cancer stem cell populations impact therapeutic options and patient outcomes.
Smoking Cessation and the Risk of Bladder Cancer among Postmenopausal Women
Authors: Li Yueyao , Tindle Hilary A. , Hendryx Michael S. , Xun Pengcheng , He Ka , Liang Xiaoyun , Luo Juhua
Published: May 2019

Smoking is the strongest established risk factor for bladder cancer. Former smokers have a lower risk of bladder cancer compared with current smokers, but findings on the dose–response relationship between years after quitting and the risk of bladder cancer are inconsistent. A total of 143,279 postmenopausal women from the Women's Health Initiative Study were included. Cox proportional hazards regression models were applied for estimating age- and multivariable-adjusted HRs and their 95% confidence intervals (CI). There were 870 bladder cancer cases identified over an average of 14.8 years of follow-up. After adjusting for pack-years of smoking, bladder cancer risk among former smokers declined by 25% within the first 10 years of cessation and continued to decrease as cessation time increased but remained higher than never smokers after 30 years of quitting (HR, 1.92; 95% CI, 1.43–2.58). Smokers who quit smoking had a lower risk of bladder cancer compared with current smokers (HR, 0.61; 95% CI, 0.40–0.94). We conclude that among postmenopausal women, there is a significant reduction in the risk of bladder cancer after quitting smoking. In addition to primary prevention, smoking cessation is critical to prevent the incidence of bladder cancer in older women.
Poor Response to Neoadjuvant Chemotherapy Correlates with Mast Cell Infiltration in Inflammatory Breast Cancer
Authors: Reddy Sangeetha M. , Reuben Alexandre , Barua Souptik , Jiang Hong , Zhang Shaojun , Wang Linghua , Gopalakrishnan Vancheswaran , Hudgens Courtney W. , Tetzlaff Michael T. , Reuben James M. , Tsujikawa Takahiro , Coussens Lisa M. , Wani Khalida , He Yan , Villareal Lily , Wood Anita , Rao Arvind , Woodward Wendy A. , Ueno Naoto T. , Krishnamurthy Savitri , Wargo Jennifer A. , Mittendorf Elizabeth A.
Published: May 2019

Our understanding is limited concerning the tumor immune microenvironment of inflammatory breast cancer (IBC), an aggressive form of primary cancer with low rates of pathologic complete response to current neoadjuvant chemotherapy (NAC) regimens. We retrospectively identified pretreatment (N = 86) and matched posttreatment tissue (N = 27) from patients with stage III or de novo stage IV IBC who received NAC followed by a mastectomy. Immune profiling was performed including quantification of lymphoid and myeloid infiltrates by IHC and T-cell repertoire analysis. Thirty-four of 86 cases in this cohort (39.5%) achieved a pathologic complete response. Characterization of the tumor microenvironment revealed that having a lower pretreatment mast cell density was significantly associated with achieving a pathologic complete response to NAC (P = 0.004), with responders also having more stromal tumor-infiltrating lymphocytes (P = 0.035), CD8+ T cells (P = 0.047), and CD20+ B cells (P = 0.054). Spatial analysis showed close proximity of mast cells to CD8+ T cells, CD163+ monocytes/macrophages, and tumor cells when pathologic complete response was not achieved. PD-L1 positivity on tumor cells was found in fewer than 2% of cases and on immune cells in 27% of cases, but with no correlation to response. Our results highlight the strong association of mast cell infiltration with poor response to NAC, suggesting a mechanism of treatment resistance and a potential therapeutic target in IBC. Proximity of mast cells to immune and tumor cells may suggest immunosuppressive or tumor-promoting interactions of these mast cells.
Estrutura e objetivos da transposição do rio São Francisco: versões de uma mesma história
Authors: Pires Ana Paula Novais
Published: May 2019

O Rio São Francisco, ou Velho Chico, é o maior rio totalmente situado em território nacional e escoa superficialmente por 2.700 km entre a nascente, na Serra da Canastra (MG), à foz, entre Sergipe (SE) e Alagoas (AL). Nesse sentido, a transposição do Rio São Francisco para as bacias hidrográficas do Nordeste Setentrional ganhou importância no cenário nacional, notadamente, pela importância sociocultural do rio para o país. O presente artigo, por meio de uma abordagem qualitativa, tem como mote compreender a transposição do rio São Francisco em seus aspectos históricos, estruturais e políticos. A transposição representa na política hídrica nacional uma situação conflituosa entre o comitê gestor das águas do Velho Chico e o Governo Federal, responsável pelo projeto e pelas obras da transposição.
A expansão da securitização imobiliária: uma prospecção a partir da cidade de Ribeirão Preto/SP
Authors: Melazzo Everaldo Santos , Abreu Marlon Altavini de
Published: May 2019

Este artigo analisa a disseminação de mecanismos de securitização de ativos de base imobiliária, contextualizando-a no crescente processo de transformação da terra, da habitação e da cidade em ativos financeiros que, a partir da antecipação de rendas futuras (principalmente fundiárias), alimenta circuitos por onde circulam e se valorizam diferentes capitais. O termo disseminação é aqui tratado em três vertentes: a primeira, ao se debruçar sobre o caso da cidade de Ribeirão Preto/SP, amplia o debate para a identificação dos processos analisados em cidades médias e não exclusivamente em realidades metropolitanas como parte da literatura nacional e internacional insiste em focar; a segunda, ao constatar que tais processos, antes restritos a vetores seletivos de valorização imobiliária na cidade, tem se disseminado espacialmente em direção a diferentes áreas e bairros da cidade, capturando para sua lógica aqueles que anteriormente eram considerados como de baixas liquidez e inserção no mercado imobiliário e, a terceira, ao constatar a presença cada mais significativa de imóveis residenciais no conjunto dos bens imobiliários securitizados. Além de reforçar a convicção sobre um paulatino e crescente processo de transformação cada vez mais intenso da terra e da habitação em ativos de valor, distancia-os cada vez mais do significado de direito à cidade que seu acesso pode significar.
“Quanta decepção me esperava fora dos limites da nossa casa”: geografias afetivas do habitar em Lavoura Arcaica, de Raduan Nassar
Authors: Souza Júnior Carlos Roberto Bernardes de
Published: May 2019

Romance publicado originalmente em 1975, “Lavoura Arcaica” narra a história da partida e retorno do filho do meio de uma família camponesa. No enredo em fluxo de consciência, André, o protagonista, descreve suas experiências, percepções e condições de habitar no âmago do lugar-lavoura. Pelo ordenamento da família que se divide em função de divergentes formas de conceber as geografias afetivas do lar conformam espacialidades de tensão. O artigo problematiza, por meio de hermenêutica embasada na fenomenologia existencialista de Merleau-Ponty, de que modo irradiam as contradições do habitar na geograficidade da experiência de André. É evidenciado que pela dinamicidade corpo-espacial tem gênese uma forma de habitar o lugar em que o emergir do ser-no-mundo é profundamente imbricado pelas emoções e percepções. Na potencialidade de ser-no-lar, o lugar se redefine contextualmente aos tensionamentos que modificam como é sentida a realidade geográfica. Conclui-se que pela corporeidade inerente ao entrelaçamento sujeito-lugar ressaltam-se os fluxos afetivos pelos quais o ser humano projeta sua consciência intencional rumo ao mundo.
Encontros e diferenças: gêneros, sexualidades e racialidades no fazer científico da geografia. Resenha de SILVA, J. M.; ORNAT, M. J.; CHIMIN JR., A. B. Geografias feministas e das sexualidades: encontros e diferenças
Authors: Silva Elisabete de Fátima Farias
Published: May 2019

“Geografias Feministas e das Sexualidades: encontros e diferenças”, organizado pelos geógrafos Joseli Maria Silva (UEPG), Marcio Jose Ornat (UEPG) e Alides Baptista Chimin Junior (Unicentro), é uma obra preciosa à geografia brasileira. Composta por dez artigos, sendo nove traduções anglófonas, a coletânea é fruto de uma decisão de pronunciamento sobre escolhas e escalas espaciais, com o objetivo de produzir uma geografia capaz de trazer sujeitos generificados, sexualizados e racializados para o centro do debate científico.O subtítulo encontros e diferenças está presente tanto no conjunto da obra, quanto nas bases teóricas bem articuladas nos artigos. Publicado em 2016, este livro é parte da produção científica do Grupo de Estudos Territoriais (GETE), formado em 2003, na Universidade Estadual de Ponta Grossa, Paraná.  O GETE trouxe novas questões para a análise espacial, pautadas no gênero e nas sexualidades, em contraponto às abordagens heteronormativas, confirma Miguel Angelo Ribeiro no prefácio. Além da organização dos artigos proporcionar uma vasta e, sobretudo, consistente aproximação com a diversidade de pesquisas já realizadas no campo das geografias feministas e sexualidades, o primeiro artigo de autoria dos brasileiros organizadores da obra traz à luz discussões muito pertinentes e atuais em “Sobre as desobediências epistemológicas e o testamento intelectual de Milton Santos”.
A paisagem e o geográfico do espaço: o onde da ontologia em geografia
Authors: Coutinho Bernard Teixeira
Published: May 2019

A percepção parece ser o termo mais ligado ao conceito paisagem, o mais difundido, estudado e, concomitantemente, o mais confuso. Ao mesmo tempo em que transfere ao conceito condições de esclarecimento, difunde questões variadas como aquelas de natureza metódica e metodológica. Nosso esforço, aqui, é pensar o percebimento sobre a paisagem por uma orientação ontológica, de modo a travar relações com a prática da abstratividade do trabalho intelectual e com o geográfico do espaço.
O sagrado e o profano na poesia de Mário de Andrade
Authors: Natal Caion Meneguello
Published: May 2019

O artigo aborda a relação entre sagrado e profano na poesia de Mário de Andrade em princípios da década de 1920. São analisados seis poemas: “Noturno”, “Jorobabel”, “XXXIII”, “XXXIII (bis) Platão”, “Carnaval carioca” e “Religião”. Para tanto, dialogamos com o conceito de “verso harmônico”, tal como exposto no manifesto vanguardista “Prefácio interessantíssimo”,  publicado no livro Pauliceia desvairada (1922). O objetivo é mostrar como o eixo sagrado-profano relaciona-se a dualidades mais gerais presentes nos versos do autor modernista, como vida e escrita,  humano e divino, linguagem e realidade, entre outros.
Rastros de cinema na teia literária urbana de Caio Fernando Abreu
Authors: Kogure Linda , Esteves Junior Milton
Published: May 2019

A meta é verificar de que forma os rastros de cinema são tecidos nos fios literários de “Pela noite”, de Caio Fernando Abreu, e por que seus personagens olham o mundo como se fosse cinema. Seriam reflexos da própria conversão do mundo contemporâneo em rastros de cinema e/ou de simulacros, que incluem também outros elos da indústria cultural? Seriam reflexos de uma experiência urbana percebida como telas em movimento, fruto de vivências mediadas por vidros, janelas e para-brisas como se fossem lentes de câmeras? A novela é o ponto de partida para se repensar o quanto a indústria cultural tem alterado o comportamento humano, estabelecendo novas relações entre sujeito, mundo material e aparelhos destinados à reprodutibilidade técnicadas imagens.
Travessia do Sertão
Authors: Bolle Willi , Kupfer Eckhard Ernst
Published: May 2019

Por ocasião do bicentenário da viagem dos naturalistas alemães Spix e Martius pelo Brasil (1817-1820), dois pesquisadores e dois cineastas refizeram, em julho de 2018, um trecho daquela expedição: a travessia do sertão de Minas Gerais até a fronteira com Goiás e com a Bahia. O principal objetivo foi estudar as continuidades e as mudanças ocorridas ao longo desses 200 anos. Estes foram os lugares visitados: 1) o distrito das Minas Novas; 2) o sertão, do rio Jequitinhonha via Montes Claros e Brasília de Minas até o rio São Francisco; 3) a cidade de Januária e o Parque Nacional do Peruaçu; 4) a Serra das Araras e a Chapada Gaúcha; 5) o caminho, via Ribeirão dos Bois, rio Carinhanha e Parque Nacional Grande Sertão Veredas, até a fronteira com Goiás; 6) a volta até o rio São Francisco, nas cidades de Carinhanha e Malhada.
Do rapa ao registro
Authors: Melo Rosilene Alves de
Published: May 2019

Em 2018 a literatura de cordel foi registrada como patrimônio imaterial do Brasil pelo Inst ituto do Patrimônio Histórico e Artístico Nacional (Iphan). Este artigo problematiza essa patrimonialização, considerando o registro como resultado de um conjunto de ações mobilizadas por diversos agentes que há mais de um século promovem a difusão desse gênero enquanto forma de expressão cultural do Brasil. A partir da análise de matérias publicadas em jornais, da produção intelectual e do inventário realizado pelo Iphan, este artigo recupera alguns sentidos atribuídos à literatura de cordel ao longo do tempo. Proscrito, considerado uma leitura nefasta por autoridades policiais e parte da elite intelectual, esse gênero foi alvo de ações de repressão, como a proibição de venda e circulação de folhetos. No entanto, as práticas de repressão não arrefeceram sua presença no país através dos autores e leitores que a consideram uma expressão da voz popular, da memória e da identidade nacional.
Literatura de cordel e valorização digital
Authors: Riaudel Michel
Published: May 2019

O caso da disponibilização digital promovida pela Biblioteca Virtual Cordel da Universidade de Poitiers levanta uma série de questões relativas ao reconhecimento do direito autoral, dentro do universo da literatura de cordel e fora. Oferece assim a oportunidade de uma ref lexão sobre as práticas de cada um.
Sobre a ausência e o surgimento da noção de regionalismo na literatura brasileira
Authors: Gil Fernando Cerisara
Published: May 2019

O artigo examina a ausência da noção de regionalismo na crítica e na história literária brasileiras no século XIX, pois, ao contrário do que se entende, o conceito ingressou em nosso circuito crítico como modo de conceber a literatura brasileira somente no século XX. Nesse sentido, o ensaio investiga as razões dessa ausência, ainda que já houvesse produção literária que figurasse a vida rural/provincial, como também procura sinalizar o momento limiar do seu surgimento no pensamento literário.
Litofácies, ambientes deposicionais e ciclicidade do Grupo Paranoá: exemplo da região da Serra de São Domingos, Minas Gerais
Authors: Feitosa Icília De Lima , Alvarenga Carlos José Souza de , Martinho Caroline Thaís
Published: May 2019

Na Serra de São Domingos (SSD) afloram mais de 1.000 m de espessura de rochas mesoproterozoicas dominantemente siliciclásticas do Grupo Paranoá. Duas seções estratigráficas foram medidas e descritas na escala 1:300 e individualizadas em 11 litofácies nas seções estudadas: De (dolomito com estromatólitos), Dl (dolomito laminado), AFl (arenito fino laminado), AFm (arenito fino com marcas onduladas de onda e corrente), AFh (arenito fino com estratificação cruzada hummocky), AMc1 (arenito médio com estratificações cruzadas unidirecionais), AMc2 (arenito médio com estratificações cruzadas bidirecionais e/ou multidirecionais), AMe (arenito médio estratificado), AMs (arenito médio com geometria sigmoidal), Pl (pelito laminado) e PAht (pelito e arenito com laminação heterolítica). Cinco associações de fácies foram identificadas: FA-I caracterizada pelas litofácies PAht e AFm em subsistema de intermaré; FA-II caracterizada pelas AMc1, AMc2, AMs, AMe em subsistema de inframaré; FA- III caracterizada pela associação de litofácies AFm, AFl, AFh e Pl em subsistema de plataforma (offshore proximal) com influência de onda, maré e de tempestade; FA-IV caracterizada pelas litofácies AFl, Pl, AFh, Dl e De em subsistema de plataforma (offshore intermediáriadistal); FA-V caracterizada pela associação de litofácies Dl e De em subsistema de zona de plataforma rasa. As associações de fácies, FA-III, FA-IV e FA-V são típicas de sistema deposicional de plataforma marinha mista carbonática-siliciclástica, enquanto FA-I e FA-II caracterizam depósitos de planície de maré. Os sistemas deposicionais ao longo da SSD variam de depósitos de plataforma offshore proximal na sua base, passando em direção ao topo para o domínio de uma plataforma proximal com influência de maré (inframaré-intermaré), evidenciando um gradual e contínuo raseamento para o topo.
Petrografia e química do Granito Aripuanã, sul do Cráton Amazônico
Authors: Godoy Antonio Misson , Vieira Otávio Augusto Ruiz Paccola , Silva Jesué Antonio da , Manzano Jefferson Cassu , Araújo Larissa Marques Barbosa de , Mello Júnior Antônio Ferreira de
Published: May 2019

O termo Granito Aripuanã refere-se a um conjunto de corpos graníticos circunscritos não deformados, intrusivos em rochas da sequência metavulcanossedimentar do Grupo Roosevelt, reconhecidos na porção sul do Cráton Amazônico. O corpo granítico principal constitui um batólito ovalado com diâmetro menor que 15 km, que ocorre a norte da cidade de Aripuanã, no noroeste do estado do Mato Grosso. É constituído de hornblenda-biotita sieno a monzogranitos porfiríticos grossos, de coloração cinza ou vermelha e localmente com texturas rapakivi. Nas áreas marginais é observada uma redução de granulação das feições porfiríticas com predomínio da fácies equigranular fina, associada a resfriamento rápido. As fácies tardias comuns são constituídas de diques equigranulares de cor cinza, aplitos róseos e cinza e veios pegmatíticos. Ocorrem veios pós-magmáticos de quartzo, fluorita, muscovita em zonas de deformação rúptil, em que as rochas mostram intensa alteração hidrotermal. Esse hidrotermalismo afeta de forma heterogênea as rochas encaixantes e as rochas magmáticas, facilitando a circulação de fluidos e favorecendo a concentração de sulfetos de zinco disseminados, sempre relacionados ao fraturamento. Os granitos hospedam xenólitos de rochas paraderivadas encaixantes, de granodioritos, quartzo dioritos e rochas micáceas. Nas bordas, ocorrem veios e apófises graníticas, além de metamorfismo de contato nas rochas encaixantes. Os monzogranitos são peraluminosos e pertencem à série de alto potássio a shoshonítica, similares a granitos “ferroan”, apresentando assinatura de granito tipo A, pós-colisionais a anorogênicos e associado à evolução do Arco Magmático Jamari.
Reavaliação das condições de cristalização de granitos alcalinos ediacaranos dos domínios Rio Piranhas-Seridó e São José do Campestre, Província Borborema, NE-Brasil
Authors: Dalan Clarissa De Aguiar , Vilalva Frederico Castro Jobim , Nascimento Marcos Antônio Leite
Published: May 2019

As condições de cristalização (P, T, ƒO2) de granitos alcalinos (tipo-A) nos domínios Rio Piranhas-Seridó e São José do Campestre (NE da Província Borborema) foram reavaliadas a partir da aplicação simultânea de múltiplos geobaromômetros e geotermômetros e modelagens de cristalização. Os corpos estudados são os plútons Caxexa, Serra do Algodão, Serra do Boqueirão, Olho D’Água, Japi e Serra Negra do Norte e o stock Flores. Os resultados mostram pressões de alojamento entre 3,0 e 3,7 kbar (~11–14 km em profundidade), à exceção do plúton Japi, com pressões médias de 5,3 kbar (~20 km). Os modelamentos resultam em temperaturas de liquidus entre 885–917 e 818ºC para o stock Flores, e solidus entre 660 e 700ºC. Egirina-augita, magnésio-ferri-hornblenda e biotita cristalizam-se entre 813–822, 728–751 e 750–789ºC, respectivamente. Entre os acessórios, o geotermômetro Zr-em-titanita retorna temperaturas da ordem de 780ºC (máximas de 830ºC) para o plúton Caxexa. A cristalização ocorreu sob condições essencialmente oxidantes para a maioria dos plútons (+1,0 < ΔQFM < +2,1), à exceção do stock Flores, formado sob condições levemente mais reduzidas (ΔQFM ≈ 0,0). Os plútons associados a zonas de cisalhamento regionais são mais enriquecidos em álcalis e, em média, mais profundos, reforçando o papel do controle estrutural na colocação e no contraste químico entre os granitos. As novas estimativas são mais acuradas e contribuem para o melhor entendimento da evolução do magmatismo granítico alcalino na porção setentrional da Província Borborema.
Contrasting Effects of Pharmacological, Procedural, and Surgical Interventions on Proportionate and Disproportionate Functional Mitral Regurgitation in Chronic Heart Failure
Authors: Packer Milton , Grayburn Paul A.
Published: May 2019

Two distinct pathways can lead to functional mitral regurgitation (MR) in patients with chronic heart failure and a reduced ejection fraction. When remodeling and enlargement of the left ventricle (LV) cause annular dilatation and tethering of the mitral valve leaflets, there is a linear relationship between LV end-diastolic volume and the effective regurgitant orifice area of the mitral valve. These patients, designated as having proportionate MR, respond favorably to treatments that lead to reversal of LV remodeling and a decrease in LV volumes (eg, neurohormonal antagonists and LV assist devices), but they may not benefit from interventions that are directed only at the mitral valve leaflets (eg, transcatheter mitral valve repair). In contrast, when ventricular dyssynchrony causes functional MR attributable to unequal contraction of the papillary muscles, the magnitude of regurgitation is greater than that predicted by LV volumes. These patients, designated as having severe but disproportionate MR, respond favorably to treatments that are directed to the mitral valve leaflets or their supporting structures (eg, cardiac resynchronization or transcatheter mitral valve repair), but they may derive little benefit from interventions that act only to reduce LV cavity size (eg, pharmacological treatments). This novel conceptual framework reflects the important interplay between LV geometry and mitral valve function in determining the clinical presentation of patients, and it allows characterization of the determinants of functional MR to guide the most appropriate therapy in the clinical setting.
Heart Rate Reserve in Fontan Patients: Chronotropic Incompetence or Hemodynamic Limitation?
Authors: Claessen Guido , La Gerche Andre , Van De Bruaene Alexander , Claeys Mathias , Willems Rik , Dymarkowski Steven , Bogaert Jan , Claus Piet , Budts Werner , Heidbuchel Hein , Gewillig Marc
Published: May 2019

Background

Patients with a Fontan circulation achieve lower peak heart rates (
HR
) during exercise. Whether this impaired chronotropic response reflects pathology of the sinoatrial node or is a consequence of altered cardiac hemodynamics is uncertain. We evaluated the adequacy of
HR
acceleration throughout exercise relative to metabolic demand and cardiac output in patients with a Fontan circulation relative to healthy controls.

Methods and Results

Thirty subjects (20 healthy controls and 10 Fontan patients) underwent cardiac magnetic resonance imaging with simultaneous invasive pressure recording via a pulmonary and radial artery catheter during supine bicycle exercise to near maximal exertion. Adequacy of cardiac index, stroke volume, and
HR
reserve was assessed by determining the exercise‐induced increase (∆) in cardiac index, stroke volume, and
HR
relative to the increase in oxygen consumption (
VO
2
).
HR
reserve was lower in Fontan patients compared with controls (71±21 versus 92±15 bpm;
P
=0.001). In contrast, increases in
HR
relative to workload and
VO
2
were higher than in controls. The change in cardiac index relative to the change in
VO
2
(∆cardiac index/∆
VO
2
) was similar between groups, but Fontan patients had increased ∆
HR
/∆
VO
2
and reduced ∆ stroke volume/∆
VO
2
compared with controls. There was an early and marked reduction in stroke volume during exercise in Fontan patients corresponding with a plateau in cardiac output at a low peak
HR
.

Conclusions

In Fontan patients, the chronotropic response is appropriate relative to exercise intensity, implying normal sinoatrial function. However, premature reductions in ventricular filling and stroke volume cause an early plateau in cardiac output beyond which further increases in
HR
would be physiologically implausible. Thus, abnormal cardiac filling rather than sinoatrial node dysfunction explains the diminished
HR
reserve in Fontan patients.
Prospective Comparison of a Percutaneous Ventricular Assist Device and Venoarterial Extracorporeal Membrane Oxygenation for Patients With Cardiogenic Shock Following Acute Myocardial Infarction
Authors: Garan A. Reshad , Takeda Koji , Salna Michael , Vandenberge John , Doshi Darshan , Karmpaliotis Dimitri , Kirtane Ajay J. , Takayama Hiroo , Kurlansky Paul
Published: May 2019

Background

Cardiogenic shock (
CS
) following acute myocardial infarction (
AMI
) portends a poor prognosis. Both venoarterial extracorporeal membrane oxygenation (
VA
‐
ECMO
) and a percutaneous ventricular assist device (
pVAD
) provide hemodynamic support for patients with
CS,
but little is known about the best device for this population. We sought to compare outcomes of
AMI
patients treated with these devices.

Methods and Results

Consecutive patients with
CS
following
AMI
from April 2015 to March 2017 were enrolled prospectively if they received either device for
AMI
‐related
CS
. If patients received both devices, they were analyzed according to the first used. The primary outcome was all‐cause mortality. In total, 51 patients received
VA
‐
ECMO
or
pVAD
following
AMI
; 20 received
VA
‐
ECMO,
and 31 received
pVAD
. The mean age was 62.1±10.1 years, and 39 (76.5%) were men. Twenty‐four (47.1%) patients were ultimately supported by both devices simultaneously (20
pVAD
‐first, 4
VA
‐
ECMO
‐first). Patients treated with
pVAD
or
VA
‐
ECMO
were similar in baseline characteristics at initial device insertion except that the latter were on more vasopressors and were more likely to have an intra‐aortic balloon pump. Seventeen (33.3%) had recent cardiopulmonary resuscitation, mean lactate was 4.86±3.96 mmol/L, and mean cardiac index was 1.70±0.42 L/min per m
2
. Of the 28 (54.9%) patients surviving to discharge, 11 had received
VA
‐
ECMO
first and 17 had
pVAD
first (
P
=0.99). Survival at 1 and 2 years did not differ significantly between device groups (
P
=0.42).

Conclusions

Following
AMI
‐related
CS
,
pVAD
‐ and
VA
‐
ECMO
‐treated patients had similar outcomes. The use of both devices simultaneously was common, with almost half of patients in persistent
CS
after first device deployment.