bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemically Modified Antisense Oligonucleotide Against ARL4C Inhibits Primary and Metastatic Liver Tumor Growth
Authors: Harada Takeshi , Matsumoto Shinji , Hirota Suguru , Kimura Hirokazu , Fujii Shinsuke , Kasahara Yuuya , Gon Hidetoshi , Yoshida Toshihiko , Itoh Tomoo , Haraguchi Naotsugu , Mizushima Tsunekazu , Noda Takehiro , Eguchi Hidetoshi , Nojima Satoshi , Morii Eiichi , Fukumoto Takumi , Obika Satoshi , Kikuchi Akira
Published: January 2019

ADP-ribosylation factor-like 4c (ARL4C) is identified as a small GTP-binding protein, which is expressed by Wnt and EGF signaling and plays an important role in tubulogenesis of cultured cells and the ureters. ARL4C is little expressed in adult tissues, but it is highly expressed in lung cancer and colorectal cancer and shown to represent a molecular target for cancer therapy based on siRNA experiments. This study revealed that ARL4C is highly expressed in primary hepatocellular carcinoma (HCC) tumors and colorectal cancer liver metastases, and that ARL4C expression is associated with poor prognosis for these cancers. Chemically modified antisense oligonucleotides (ASO) against ARL4C effectively reduced ARL4C expression in both HCC and colorectal cancer cells and inhibited proliferation and migration of these cancer cells in vitro. ARL4C ASOs decreased the PIK3CD mRNA levels and inhibited the activity of AKT in HCC cells, suggesting that the downstream signaling of ARL4C in HCC cells is different from that in lung and colon cancer cells. In addition, subcutaneous injection of ARL4C ASO was effective in reducing the growth of primary HCC and metastatic colorectal cancer in the liver of immunodeficient mice. ARL4C ASO accumulated in cancer cells more efficiently than the surrounding normal cells in the liver and decreased ARL4C expression in the tumor. These results suggest that ARL4C ASO represents a novel targeted nucleic acid medicine for the treatment of primary and metastatic liver cancers.
Extracellular Fatty Acids Are the Major Contributor to Lipid Synthesis in Prostate Cancer
Authors: Balaban Seher , Nassar Zeyad D. , Zhang Alison Y. , Hosseini-Beheshti Elham , Centenera Margaret M. , Schreuder Mark , Lin Hui-Ming , Aishah Atqiya , Varney Bianca , Liu-Fu Frank , Lee Lisa S. , Nagarajan Shilpa R. , Shearer Robert F. , Hardie Rae-Anne , Raftopulos Nikki L. , Kakani Meghna S. , Saunders Darren N. , Holst Jeff , Horvath Lisa G. , Butler Lisa M. , Hoy Andrew J.
Published: January 2019

Prostate cancer cells exhibit altered cellular metabolism but, notably, not the hallmarks of Warburg metabolism. Prostate cancer cells exhibit increased de novo synthesis of fatty acids (FA); however, little is known about how extracellular FAs, such as those in the circulation, may support prostate cancer progression. Here, we show that increasing FA availability increased intracellular triacylglycerol content in cultured patient-derived tumor explants, LNCaP and C4-2B spheroids, a range of prostate cancer cells (LNCaP, C4-2B, 22Rv1, PC-3), and prostate epithelial cells (PNT1). Extracellular FAs are the major source (∼83%) of carbons to the total lipid pool in all cell lines, compared with glucose (∼13%) and glutamine (∼4%), and FA oxidation rates are greater in prostate cancer cells compared with PNT1 cells, which preferentially partitioned extracellular FAs into triacylglycerols. Because of the higher rates of FA oxidation in C4-2B cells, cells remained viable when challenged by the addition of palmitate to culture media and inhibition of mitochondrial FA oxidation sensitized C4-2B cells to palmitate-induced apoptosis. Whereas in PC-3 cells, palmitate induced apoptosis, which was prevented by pretreatment of PC-3 cells with FAs, and this protective effect required DGAT-1–mediated triacylglycerol synthesis. These outcomes highlight for the first-time heterogeneity of lipid metabolism in prostate cancer cells and the potential influence that obesity-associated dyslipidemia or host circulating has on prostate cancer progression.

Implications:

Extracellular-derived FAs are primary building blocks for complex lipids and heterogeneity in FA metabolism exists in prostate cancer that can influence tumor cell behavior.
Dual Targeting of EGFR and IGF1R in the TNFAIP8 Knockdown Non–Small Cell Lung Cancer Cells
Authors: Day Timothy F. , Kallakury Bhaskar V.S. , Ross Jeffrey S. , Voronel Olga , Vaidya Shantashri , Sheehan Christine E. , Kasid Usha N.
Published: January 2019

Aberrant regulation of EGFR is common in non–small cell lung carcinomas (NSCLC), and tumor resistance to targeted therapies has been attributed to emergence of other co-occurring oncogenic events, parallel bypass receptor tyrosine kinase pathways including IGF1R, and TNFα-driven adaptive response via NF-κB. TNFAIP8, TNFα-inducible protein 8, is an NF-κB–activated prosurvival and oncogenic molecule. TNFAIP8 expression protects NF-κB–null cells from TNFα-induced cell death by inhibiting caspase-8 activity. Here, we demonstrate that knockdown of TNFAIP8 inhibited EGF and IGF-1–stimulated migration in NSCLC cells. TNFAIP8 knockdown cells showed decreased level of EGFR and increased expression of sorting nexin 1 (SNX1), a key regulator of the EGFR trafficking through the endosomal compartments, and treatment with SNX1 siRNA partially restored EGFR expression in these cells. TNFAIP8 knockdown cells also exhibited downregulation of IGF-1–induced pIGF1R and pAKT, and increased expression of IGF-1–binding protein 3 (IGFBP3), a negative regulator of the IGF-1/IGF1R signaling. Consistently, treatment of TNFAIP8 knockdown cells with IGFBP3 siRNA restored pIGF1R and pAKT levels. TNFAIP8 knockdown cells had enhanced sensitivities to inhibitors of EGFR, PI3K, and AKT. Furthermore, IHC expression of TNFAIP8 was associated with poor prognosis in NSCLC. These findings demonstrate TNFAIP8-mediated regulation of EGFR and IGF1R via SNX1 and IGFBP3, respectively. We posit that TNFAIP8 is a viable, multipronged target downstream of the TNFα/NF-κB axis, and silencing TNFAIP8 may overcome adaptive response in NSCLC.

Implications:

TNFAIP8 and its effectors SNX1 and IGFBP3 may be exploited to improve the efficacy of molecular-targeted therapies in NSCLC and other cancers.

Visual Overview: http://mcr.aacrjournals.org/content/molcanres/17/5/1207/F1.large.jpg.
Neurotoxicity of Unconjugated Bilirubin in Mature and Immature Rat Organotypic Hippocampal Slice Cultures
Authors: Dani Carlo , Pratesi Simone , Ilari Alice , Lana Daniele , Giovannini Maria Grazia , Nosi Daniele , Buonvicino Daniele , Landucci Elisa , Bani Daniele , Mannaioni Guido , Gerace Elisabetta
Published: January 2019

Background: The physiopathology of bilirubin-induced neurological disorders is not completely understood. Objectives: The aim of our study was to assess the effect on bilirubin neurotoxicity of the maturity or immaturity of exposed cells, the influence of different unconjugated bilirubin (UCB) and human serum albumin (HSA) concentrations, and time of UCB exposure. Methods: Organotypic hippocampal slices were exposed for 48 h to different UCB and HSA concentrations after 14 (mature) or 7 (immature) days of in vitro culture. Immature slices were also exposed to UCB and HSA for 72 h. The different effects of exposure time to UCB on neurons and astrocytes were evaluated. Results: We found that 48 h of UCB exposure was neurotoxic for mature rat organotypic hippocampal slices while 72 h of exposure was neurotoxic for immature slices. Forty-eight-hour UCB exposure was toxic for astrocytes but not for neurons, while 72-h exposure was toxic for both astrocytes and neurons. HSA prevented UCB toxicity when the UCB:HSA molar ratio was ≤1 in both mature and immature slices. Conclusions: We confirmed UCB neurotoxicity in mature and immature rat hippocampal slices, although immature ones were more resistant. HSA was effective in preventing UCB neurotoxicity in both mature and immature rat hippocampal slices.
Position of Scientific Oncological Societies Towards Biosimilar Antibodies
Authors: Wörmann Bernhard , Sinn Marianne
Published: January 2019

First biosimilars of monoclonal antibodies have recently been approved in oncology. Biosimilars enable economic competition, alleviate the financial burden for insurances, and may facilitate access to these drugs in low-income countries. Biosimilars are not completely identical to the original drug. The approval of biosimilars is only partially based on results of randomized clinical studies. In the introduction phase of new biosimilars, this can lead to uncertainties for patients and physicians. Based on the current clinical data and experiences, biosimilars of monoclonal antibodies in oncology show no significant differences in pharmacokinetics, efficacy, and safety in comparison to the patented originals. Scientific medical societies recommend the use of biosimilar monoclonal antibodies and support switching in long-term treatments. However, the use of biosimilars for off-label indications requires additional attention towards efficacy and safety. Active counselling of the patient by the treating physician is the most important step in the informed consent process, especially when switching from an original to a biosimilar. Careful documentation of the prescribed drug and enhanced pharmacovigilance are recommended for the use of biosimilars.
Syndromic Craniosynostosis: Complexities of Clinical Care
Authors: O''Hara Justine , Ruggiero Federica , Wilson Louise , James Greg , Glass Graeme , Jeelani Owase , Ong Juling , Bowman Richard , Wyatt Michelle , Evans Robert , Samuels Martin , Hayward Richard , Dunaway David J.
Published: January 2019

Patients with syndromic craniosynostosis have a molecularly identified genetic cause for the premature closure of their cranial sutures and associated facial and extra-cranial features. Their clinical complexity demands comprehensive management by an extensive multidisciplinary team. This review aims to marry genotypic and phenotypic knowledge with clinical presentation and management of the craniofacial syndromes presenting most frequently to the craniofacial unit at Great Ormond Street Hospital for Children NHS Foundation Trust.
1q42.12q42.2 Deletion in a Child with Midline Defects and Hypoplasia of the Corpus Callosum
Authors: Radha Rama Devi Akella , Ganapathy Aparna , Mannan Ashraf U. , Sabharanjak Shefali , Naushad Shaik M.
Published: January 2019

Chromosome 1q42.12q42.2 deletions are documented as “disease causing” and show overlapping phenotypes depending on the genes involved in the deletion. In this report, we detected a 5.8-Mb deletion encompassing the chromosome 1q42.12q42.2 region in a 4-year-old boy with hypoplastic corpus callosum, epilepsy, developmental delay, microcephaly, cataract, cleft palate, and skeletal changes. The deletion was de novo. Genotype-phenotype correlations suggest that the major features of 1q42.12q42.2 microdeletion were attributed to the genes with a high probability of loss-of-function intolerance score in this deletion, namely LBR, ENAH, ACBD3, LIN9, ITPKB, CDC42BPA, ARF1, TAF5L, GALNT2, SPRTN, and EGLN1 along with GNPAT.
Angelos Katakouzenos (1902–1982): A Lifework of Neurology and Art
Authors: Stefanou Maria-Ioanna , Peloponnissiou-Vassilacos Sophia
Published: January 2019

Angelos Katakouzenos, a Greek neurologist and prolific medical writer at the beginning of the 20th century, belonged to a group of artists and scholars that formed the “generation of the 30s,” a cultural movement that emerged after World War I and introduced modernism in Greek art and literature. Born in 1902, Katakouzenos studied medicine in France at the Universities of Montpellier and Paris, where he trained in neurology and ­psychiatry under Georges Guillain, Henri Claude, Jean-Athanase Sicard, Pierre Marie, Clovis Vincent and Théophile ­Alajouanine. In Paris, he attended to Freud’s patients, collaborating with the psychoanalyst Marie Bonaparte, while he was introduced to the contemporary avant-garde movements of this time, developing long-lasting friendships with artists and intellectuals, including Marc Chagall and Tériade. Although Professor of Neurology and Psychiatry at the University of ­Paris, Commandeur of the Légion d’honneur and founder of the first neuropsychiatric clinics in Greece, Katakouzenos lived far from the limelight. Despite his numerous publications, his scientific work remained largely unacknowledged. Yet, as a ­psychoanalyst he gained international fame and treated patients including William Faulkner who later would write, “To the wise scientist, the in-depth judge of the human soul, my friend Dr. Katakouzenos, who has helped me like no one else to redeem myself from the tortuous questions that troubled me for years – from the depths of my heart, many, very many thanks”. In this paper, the rediscovery of Katakouzenos’s remarkable work in the field of neuroscience aims to tell the story of a great physician whose lifework in bridging art and science may, in retrospect, reinstate him as one of the most captivating neurologists of the 20th century.
Recovery of Adrenal Function after Pituitary Surgery in Patients with Cushing Disease: Persistent Remission or Recurrence?
Authors: Serban Andreea Liliana , Sala Elisa , Carosi Giulia , Del Sindaco Giulia , Giavoli Claudia , Locatelli Marco , Arosio Maura , Mantovani Giovanna , Ferrante Emanuele
Published: January 2019

Background: Cushing disease (CD) represents the principal cause of endogenous hypercortisolism. The first-line therapy of CD is surgical removal of the ACTH-secreting pituitary adenoma, which is generally followed by adrenal insufficiency (AI). Objective: To analyze the recovery of AI in patients with CD after pituitary surgery in relation with recurrence and persistent remission of CD. Patients and Methods: We performed a retrospective analysis of patients with CD who met the following inclusion criteria: adult age, presence of AI 2 months after the surgical intervention, and a minimum follow-up of 3 years after the surgical intervention. Results: Sixty-one patients were followed for a median of 6 years. Ten (16.4%) patients recurred during follow-up. The patients who restored adrenal function did so after a median time of 19 months, with a significantly shorter time in the recurrence group (12.5 vs. 25 months, p = 0.008). All 10 patients who recurred recovered their adrenal function within 22 months. The recovery rate of AI in the persistent remission group was 37.3% (19/51) at 3 years and 55.8% (24/43) at 5 years. In all patients the duration of AI was negatively associated with disease recurrence. Conclusion: The duration of postsurgical AI in patients with recurrent CD is significantly shorter than that in patients with persistently remitted CD, and this parameter may be a useful predictor of recurrence. Patients showing a normal pituitary-adrenal axis within 2 years after surgery should be strictly monitored as they are at higher risk of disease relapse.
The Effectiveness of Different Doses of Intravenous Immunoglobulin on Severe Hand, Foot and Mouth Disease: A Meta-Analysis
Authors: Jiao Wei , Tan Si-Ran , Huang Yan-Feng , Mu Li-Hong , Yang Yang , Wang Yan , Wu Xue-E
Published: January 2019

Objective: To conduct a meta-analysis of evidence from randomized controlled trails (RCTs) of different doses of intravenous immunoglobulin (IVIG) in children with severe hand, foot and mouth disease (HFMD) to provide the scientific basis for clinical practice. Methods: A search of PubMed-Medline, CNKI, Wanfang, and VIP database (until June 30, 2017) was performed and Software RevMan5.3 was used to evaluate the effect of different doses of IVIG on HFMD in RCTs. We used random-effects models (or fixed-effects models) and generic inverse variance methods to process quantitative data, followed by a leave-one-out method for sensitivity analysis. Results: From a total of 420 entries identified via searches, 8 RCTs involving 1,450 patients were included in the final analysis. The results of the meta-analysis showed that compared with conventional therapy alone, conventional therapy combined with IVIG had shorter fever clearance time, shorter rash regression time, and shorter clinical cure time. Subgroup analyses showed that the high-dose group (1 g/kg/day) had shorter fever clearance time (p < 0.05), shorter rash regression (p< 0.05), shorter remission time of neurological symptoms (p < 0.05), but longer clinical cure time (p > 0.05). Conclusion: The high-dose group has a better prognosis; however, the advantages and disadvantages should be carefully considered when deciding the doses in the treatment of severe HFMD.
Definir ou Não Definir Arte: objeções à tese da impossibilidade da definição de arte e perspectivas teóricas após Morris Weitz
Authors: Morokawa Rosi Leny
Published: January 2019

Este artigo trata da proposta apresentada por Morris Weitz de que não é possível definir arte em termos de condições necessárias e suficientes. Ele sustenta que as teorias em estética, ao buscarem uma definição que capture a essência da arte, tentam definir o que não pode ser definido. Este artigo mostra que o argumento de Weitz – centrado no uso do conceito de arte como “conceito aberto” e na análise da extensão do termo “arte” – é refutável por objeções que envolvem a noção de “semelhança de família”. Além disso, aponta-se duas perspectivas para o debate sobre a possibilidade de definir arte: uma que retoma a posição de Weitz e outra que propõe definições nos termos negados por ele.
A questão da moda moderna brasileira no Instituto de Arte Contemporânea do Museu de Arte de São Paulo (IAC-Masp) entre 1950 e 1953
Authors: Scarpa Soraia Pauli , Kanamaru Antonio Takao
Published: January 2019

Trata-se de estudo sobre a importância histórica de iniciativas e obras em relação à moda moderna brasileira, no espaço pioneiro do Instituto de Arte Contemporânea do Museu de Arte de São Paulo (IAC-Masp) no contexto de suas atividades entre 1950 e 1953. Análise baseada no periódico Habitat, principal órgão modernista do Masp, bem como na revista O Cruzeiro. Foi proposto contribuir com a abordagem desse capítulo da moda moderna brasileira, pouco valorizado, mas relevante naquele contexto bem como nos dias atuais.
Entrevendo olhares espectrais: as fotografias de vítimas das ditaduras em obras de arte contemporâneas
Authors: Santos Ana Carolina Lima
Published: January 2019

Este artigo analisa os catálogos de três exposições apresentadas no Memorial da Resistência de São Paulo que têm como principal material expressivo fotografias de mortos e desaparecidos políticos, vítimas das ditaduras civil- militares da Argentina, do Brasil e do Chile. “Buena memoria”, de Marcelo Brodsky, “Ausenc’as”, de Gustavo Germano, e “119”, de Cristian Kirby, são examinados pelo modo como mobilizam esses retratos, destacados em suas estratégias próprias. Guardadas as singularidades de cada trabalho, a análise aponta neles uma potência comum: a capacidade de agenciar os olhares encarnados nas imagens, que então podem mirar de volta os espectadores para deles exigir recordação, responsabilização e redenção.
Formalismo de quem?
Authors: Bois Yve-Alain , Euvaldo Célia
Published: January 2019

Lançando mão de uma refutação meticulosa dos que o “acusam” de um formalismo de tipo greenberguiano, o autor replica a seus “acusadores”, declarando suas conexões profundas a linhagens históricas do formalismo, cujas origens remontam a Alois Riegl, ao formalismo russo e ao estruturalismo – a milhas de distância, ele sublinha, da busca idealista de Greenberg por uma ideia sublimatória de forma. Ao longo do artigo, Yve-Alain Bois declara de modo enfático o mais vivo interesse na significação histórica do trabalho de arte e sua convicção no enraizamento da forma na matéria histórica, contrariamente à condenação greenberguiana de quaisquer injunções do significado nessa discussão.
Ler Nietzsche como “nietzschiano”: questões de método
Authors: Marton Scarlett
Published: January 2019

Tomando como ponto de partida a análise das passagens em que Nietzsche fornece a seus leitores as indicações de como desejaria ser lido, este artigo conta, num primeiro momento, mostrar a sua insuficiência. Propondo-se discutir questões metodológicas, pretende evidenciar a especificidade do texto nietzschiano e as formas de abordá-lo.
Vontade de nada e vontade de saúde nos escritos tardios de Nietzsche
Authors: Araldi Clademir Luís
Published: January 2019

Nos escritos de 1888, Nietzsche retoma com interesse redobrado duas formas antagônicas da vontade: a vontade de saúde e a vontade de nada. Investigaremos, a partir da discussão com Scarlett Marton, se e como as atitudes sadias do próprio Nietzsche decorrem de suas condições fisiológicas e, no contexto dos dois primeiros capítulos de Ecce Homo, em que medida a configuração pulsional de Nietzsche dita a sua terapêutica e sua tarefa filosófica. Da perspectiva do Nietzsche ‘saudável’, a vontade de saúde predominaria sobre a vontade de nada. Num segundo momento, questionaremos a afirmação de Nietzsche, de que ele seria “fundamentalmente sadio”, a partir dos textos de 1885 a 1888, em que ele investiga também a vontade de nada. Enquanto doente, ele poderia ser médico de si mesmo e, com isso, médico da cultura? Admitindo sua dupla natureza, o Filósofo doente poderia investigar o trabalho secreto do instinto da decadência sem ser por ele influenciado?

Palavras-chaveVontade de Saúde; Vontade de Nada; Instinto; Niilismo; Transvaloração.
Sub specie saeculi, sub specie aeterni: tempo e eternidade no jovem Nietzsche
Authors: Nasser Eduardo
Published: January 2019

Para o jovem Nietzsche, a modernidade marca o início do ocaso da cultura ocidental em virtude da glorificação do conhecimento. Esse aspecto é a causa para que o homem moderno fique enclausurado numa perspectiva realista, sendo incapaz de se libertar do constrangimento infligido pelo vir-a-ser. Para reverter a condenação imposta à cultura pelo socratismo, é preciso restituir os direitos da arte, pois somente a arte viabiliza a recuperação do laço com a eternidade, fornecendo meios para o homem se proteger dos efeitos do tempo. Isso ocorre especialmente no âmbito da arte musical, quer em sua vertente apolínea (ritmo), quer em sua vertente dionisíaca (harmonia), na medida em que a supremacia das aparências ante a arte é enfraquecida.

Palavras-chaveTempo; Eternidade; Linguagem; Arte; Mito.
A fisiopsicologia de Nietzsche: o diagnóstico e a elevação da cultura como tarefa do médico filosófico
Authors: Frezzatti Jr. Wilson Antonio
Published: January 2019

As produções humanas, segundo Nietzsche, são expressões fisiológicas, ou seja, expressões de um conjunto de impulsos em luta por mais potência. Essa perspectiva ocupa papel central nas reflexões da maturidade do filósofo: sua fisiopsicologia desenvolve um diagnóstico das produções culturais e indica quais manifestações possuem um caráter saudável e quais delas são doentias. Nietzsche assume o papel de médico na medida em que se preocupa com um medicamento, isto é, com um contra-ideal, com um adversário da civilização entendida enquanto domesticação dos impulsos humanos. O médico nietzschiano antagoniza-se àquele proposto pela tradição filosófica: não é um médico de almas.

Palavras-chaveCivilização; Cultura; Fisiopsicologia; Médico filosófico; Vontade de potência.
Novel Biomarkers for the Precisive Diagnosis and Activity Classification of Takayasu Arteritis
Authors: Cui Xiao , Qin Fang , Song Lei , Wang Tian , Geng Bin , Zhang Weili , Jin Ling , Wang Wenjie , Li Shuangyue , Tian Xinping , Zhang Huimin , Cai Jun
Published: January 2019

Background:

Establishing the diagnosis and determining disease activity of Takayasu arteritis (TA) remains challenging. Novel biomarkers might help to solve this problem.

Methods:

In the screening phase, by using large-scale protein arrays detecting samples from 90 subjects (TA active, 29; TA inactive 31; and controls, 30). In the validation phase, by using enzyme-linked immunosorbent assay (ELISA), potential biomarkers for TA diagnosis, and activity classification were measured in independent cohorts, respectively.

Results:

In the screening phase, 18 cytokines significantly differentially enriched between TA patients and controls and another 15 cytokines significantly differentially enriched between TA patient in active and inactive status were identified (adjusted
P
<0.05). In the validation phase, TIMP (tissue inhibitor of metalloproteinases)-1 was identified as a specific biomarker for TA diagnosis that a cutoff value of 221.86 μg/L could provide a specificity of 89.58% and a positive predictive value of 0.92. Meanwhile, we found it unreliable to use a single biomarker for TA activity classification. Considering this, we further built a logistic regression model based on multiple cytokines, including CA (cancer antigen) 125, FLRG (follistatin-related protein), IGFBP (insulin-like growth factor-binding protein)-2, CA15-3, GROa (growth-regulated alpha protein), LYVE (lymphatic vessel endothelial hyaluronic acid receptor)-1, ULBP (UL16-binding protein)-2, and CD (cluster of differentiation) 99, with an area under the curve reaching 0.909 for discriminating TA activity status.

Conclusions:

This study suggested TIMP-1 as a specific biomarker for TA diagnosis with a cutoff value of 221.86 μg/L. Furthermore, we provided a logistic regression model based on 8 biomarkers for the precisive activity classification of TA with an area under the curve of 0.909.
Familial Sinus Node Disease Caused by a Gain of GIRK (G-Protein Activated Inwardly Rectifying K
+
Channel) Channel Function
Authors: Kuß Johanna , Stallmeyer Birgit , Goldstein Matthias , Rinné Susanne , Pees Christiane , Zumhagen Sven , Seebohm Guiscard , Decher Niels , Pott Lutz , Kienitz Marie-Cécile , Schulze-Bahr Eric
Published: January 2019

Background:

Inherited forms of sinus node dysfunction (SND) clinically include bradycardia, sinus arrest, and chronotropic incompetence and may serve as disease models to understand sinus node physiology and impulse generation. Recently, a gain-of-function mutation in the G-protein gene
GNB2
led to enhanced activation of the GIRK (G-protein activated inwardly rectifying K
+
channel). Thus, human cardiac GIRK channels are important for heart rate regulation and subsequently, genes encoding their subunits Kir3.1 and Kir3.4 (
KCNJ3
and
KCNJ5
) are potential candidates for inherited SND in human.

Methods:

We performed a combined approach of targeted sequencing of
KCNJ3
and
KCNJ5
in 52 patients with idiopathic SND and subsequent whole exome sequencing of additional family members in a genetically affected patient. A putative novel disease-associated gene variant was functionally analyzed by voltage-clamp experiments using various heterologous cell expression systems (Xenopus oocytes, CHO cells, and rat atrial cardiomyocytes).

Results:

In a 3-generation family with SND we identified a novel variant in
KCNJ5
which leads to an amino acid substitution (p.Trp101Cys) in the first transmembrane domain of the Kir3.4 subunit of the cardiac GIRK channel. The identified variant cosegregated with the disease in the family and was absent in the Exome Variant Server and Exome Aggregation Consortium databases. Expression of mutant Kir3.4 (±native Kir3.1) in different heterologous cell expression systems resulted in increased GIRK currents (
I
K,ACh
) and a reduced inward rectification which was not compensated by intracellular spermidine. Moreover, in silico modeling of heterotetrameric mutant GIRK channels indicates a structurally altered binding site for spermine.

Conclusions:

For the first time, an inherited gain-of-function mutation in the human GIRK3.4 causes familial human SND. The increased activity of GIRK channels is likely to lead to a sustained hyperpolarization of pacemaker cells and thereby reduces heart rate. Modulation of human GIRK channels may pave a way for further treatment of cardiac pacemaking.
Hemorrhagic Transformation After Thrombectomy for Tandem Occlusions
Authors: Zhu François , Labreuche Julien , Haussen Diogo C. , Piotin Michel , Steglich-Arnholm Henrik , Taschner Christian , Papanagiotou Panagiotis , Lapergue Bertrand , Dorn Franziska , Cognard Christophe , Killer Monika , Psychogios Marios N. , Spiotta Alejandro , Mazighi Mikael , Bracard Serge , Turjman Francis , Richard Sébastien , Gory Benjamin ,   the TITAN (Thrombectomy in Tandem Lesions) Investigators
Published: January 2019

Background and Purpose—

Carotid artery stenting in tandem large vessel occlusion strokes is usually avoided because of the intracranial hemorrhagic risks induced by antiplatelet therapy during thrombectomy interventions. This study aimed to evaluate the incidence of hemorrhagic transformation following thrombectomy in large vessel occlusion strokes patients with atherosclerotic cervical carotid occlusion, associated factors, and clinical relevance.

Methods—

The TITAN (Thrombectomy in Tandem Lesions) collaboration pooled individual data of prospectively collected multicentric thrombectomy databases for consecutive anterior circulation tandem large vessel occlusion strokes patients who underwent thrombectomy. Hemorrhagic infarction (HI) and parenchymal hematoma (PH) were assessed within 24 hours.

Results—

Among 289 patients with atherosclerotic cause, 66 (24.7%) patients developed HI and 38 (14.2%) PH. Intracranial carotid occlusion, diabetes mellitus, absence of prior intravenous thrombolysis, and complete extracranial carotid occlusion were independent predictors of HI. Similar predictors were found for PH with addition of higher baseline National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score <7. No detrimental effect of HI on 90-day clinical outcome was found. The occurrence of PH was associated with increased mortality rates (adjusted odds ratio, 2.63; 95% CI, 1.05–6.59;
P
=0.039) and had no detrimental effect on 90-day modified Rankin Scale 0 to 2 (adjusted odds ratio, 0.52; 95% CI, 0.20–1.28;
P
=0.25).

Conclusions—

Incidence of PH after tandem large vessel occlusion strokes thrombectomy is equivalent to those reported in the literature data for isolated occlusions. Similar predictors were found for PH and HI within 24 hours, whereas acute carotid artery stenting and antiplatelet therapy were not, suggesting an aggressive endovascular treatment of tandem occlusions.
Forgetting Memories and Their Attractiveness
Authors: Marinari Enzo
Published: January 2019

We study numerically the memory that forgets, introduced in 1986 by Parisi by bounding the synaptic strength, with a mechanism that avoids confusion; allows remembering the pattern learned more recently; and has a physiologically very well-defined meaning. We analyze a number of features of this learning for a finite number of neurons and finite number of patterns. We discuss how the system behaves in the large but finite [Formula: see text] limit. We analyze the basin of attraction of the patterns that have been learned, and we show that it is exponentially small in the age of the pattern.
Laypeople’s Beliefs Affect their Reports about the Subjective Experience of Time
Authors: Lee Yee Mun , Janssen Steve M. J.
Published: January 2019

Because the general population may be familiar with the phenomenon that life appears to speed up as people become older, participants’ preconceptions may affect how they answer questionnaires about the subjective experience of time. To be able to account for these preconceptions in future research, we assessed laypeople’s beliefs about the phenomenon. Participants (N = 313) were asked whether they were familiar with the phenomenon, whether they experienced the phenomenon themselves, and what they thought that the cause or causes of the phenomenon might be. More than 80% of the participants had read or heard about the phenomenon prior to the study, suggesting that the phenomenon is well known among the general population. Furthermore, although most participants experienced the phenomenon themselves, familiarity with the phenomenon affected whether they felt that life appeared to be speeding up and whether time passed fast for them. Familiarity also affected whether participants attributed the phenomenon to changes in objective or subjective time but not the endorsement of the phenomenon’s causes. Finally, participants also had preconceptions about what time periods represent ‘the present’ and ‘the past’. Whereas nearly all participants considered the past to have lasted more than one year, two-third of the participants felt that the present represented a period less than one year.
Angusticopula rowlingiana, a new melosiroid diatom (Bacillariophyta) from Ascension Island (South Atlantic Ocean)
Authors: VAN DE VIJVER BART , WILFERT SANDRA , HOUK VACLAV , JOHN DAVID M.
Published: January 2019

During a diatom survey of some samples from Ascension Island, a remote island located in the southern Atlantic Ocean, an unknown melosiroid diatom species was studied using both light and scanning electron microscopy. It proved to be a new species described as Angusticopula rowlingiana sp. nov. and characterized by a large number of narrow copulae in the girdle, a marginal ring of small granules, very small pores covering the entire valve face and occasionally having internal valves.                The new species is compared with all Angusticopula species known worldwide and with several Melosira species showing a similar combination of characters. Short notes on its ecology are included.
Contributions to the systematics of the genera Dipseudopsis, Hyalopsyche and Pseudoneureclipsis (Trichoptera: Dipseudopsidae), with descriptions of 19 new species from the Oriental Region
Authors: OLÁH JÁNOS , JOHANSON KJELL ARNE
Published: January 2019

Nineteen new species of Dipseudopsidae from the Oriental Region are described and illustrated, including 6 new species of the genus Dipseudopsis: D. cocon, D. oliveri, D. gunung, D. rathnotoia, D. vienha, and D. viklundi; 2 new species of the genus Hyalopsyche: H. trunga and H. orissa; and 11 new species of the genus Pseudoneureclipsis: P. bonkybin, P. boquan, P. cauky, P. congkem, P. dongian, P. hailan, P. halongensis, P. loang, P. puyah, P. quancong, and P. vetcat. The genus Hyalopsychella Ulmer, 1930, is recognized as a new synonym of Hyalopsyche Ulmer, 1904. Hyalopsyche parvispinosa Schmid, 1959, and H. parvula Martynov, 1935, are recognized as new synonyms of H. sachalinica Martynov, 1910; Hyalopsyche similis Martynov, 1935, is recognized as a new synonym of Hyalopsychodes rivalis Betten, 1909; and Hyalopsychella haplotes Neboiss, 1989, is recognized as a new synonym of Hyalopsyche winkleri (Ulmer, 1930). New records of 14 other species are provided.
Revision of Ootheca Chevrolat, 1837 from tropical Africa—redescriptions, descriptions of new species and identification key (Coleoptera: Chrysomelidae, Galerucinae)
Authors: KORTENHAUS SABINE , WAGNER THOMAS
Published: January 2019

The Afrotropical species of Ootheca Chevrolat, 1837 are revised based on examination of 9560 specimens. Crioceris mutabilis Sahlberg, 1829, the type species, is redescribed including comprehensive illustrations of its external and genitalic characters. Synonymy with Ergana Chapuis, 1879 is confirmed. Genitalic structures, in particular the median lobe, allow reliable species identification in this genus. Of the 33 species originally described in Ootheca and Ergana, eleven remain in Ootheca, with four new synonymies, resulting in the following nine valid species: O. mutabilis (Sahlberg, 1829) (= Malacosoma bicolor Allard, 1889 syn. nov.; = O. punctata Laboissière, 1931 syn. nov.); O. proteus (Chapuis, 1879) (= E. bifrons Laboissière, 1937 syn. nov.); O. chapuisi (Jacoby, 1899); O. bennigseni Weise, 1900 (= E. variceps Laboissière, 1939 syn. nov.); O. orientalis Weise, 1900; O. kibonotensis Weise, 1909; O. variabilis (Laboissière, 1920); O. frontalis Laboissière, 1923, O. meridiana Grobbelaar, 2008. Four species are herein described as new: O. eddae sp. n., O. julianae sp. n., O. tilmani sp. n., and O. ugandae sp. n. Redescriptions or descriptions are given for each of the 13 species, including illustrations of habitus outline, colouration, shape of basal antennomeres and the median lobe. Studied material is listed in detail, photographs of the primary types, distribution maps and a key are given. The 22 remaining described species from Ootheca have been previously transferred to other genera or will be in subsequent publications.
Taxonomic characterization of Paradoxical frogs (Anura, Hylidae, Pseudae): geographic distribution, external morphology, and morphometry
Authors: GARDA ADRIAN ANTONIO , SANTANA DIEGO JOSÉ , DE AVELAR SÃO-PEDRO VINÍCIUS
Published: January 2019

Paradoxical frogs (Pseudae) have been difficult to characterize morphologically, and their phylogenetic affinities have long remained elusive despite several taxonomic revisions of the group. Based on the analysis of 1388 specimens we evaluate morphological characters used to identify and group species throughout their distributions. We also suggest other, previously unreported phylogenetically informative morphological characters and evaluate morphometric differences among species. The geographic distribution of Pseudae in Brazil confirms, to a certain degree, their association with hydrographic basins. Geographic variation in morphology is extensive in some species. Some characters traditionally used to identify species (e.g. stripes on the ventral surface of the thigh) vary extensively among populations, and in most cases do not distinguish among species. Body shape differences, skin texture, size and number of carpal and metatarsal tubercles, supernumerary tubercles, vocal sac structure, dorsal coloration, ventral stripes on the thigh, and geographic distribution need to be considered together to correctly identify species. Size of reproductive Pseudis varies considerably, most likely as a response to local conditions altering larval size at metamorphosis, given that postmetamorphic growth is reduced or absent in Pseudis. The previously suggested suite of ecological characters that allow disproportionate larval growth are therefore substantiated, while the paradox of a conserved body plan coupled with extensive character variation is implicated as the cause for confusion in the taxonomy of paradoxical frogs.
Marine fishes from Galicia (NW Spain): an updated checklist
Authors: BAÑON RAFAEL , VILLEGAS-RÍOS DAVID , SERRANO ALBERTO , MUCIENTES GONZALO , ARRONTE JUAN CARLOS
Published: January 2019

An annotated checklist of the marine fishes from Galician waters is presented. The list is based on historical both literature records and on new revisions. The ichthyofauna list is composed by 398 species. It is diversified in 2 superclasses, 3 class, 35 orders, 139 families and 288 genuses. Perciformes is the most diverse order with 37 families, 91 genus and 136 species. Gobiidae (19 species) and Sparidae (19 species) are the richest families. Biogeographically, the Lusitanian is the most important group including 204 species (51.3%), followed by the Atlantic group with 149 species (37.4%), the Boreal group with 28 species (7%) and the 17 species (4.3%) of the African group. A total of 42 species have been included as new records for the study area, and 3 records have been identified as doubtful. Identification and registration of errors from previous studies have been also indicated.
Annotated checklist of the snapping shrimps of the genus Alpheus Fabricius, 1798 (Crustacea: Decapoda: Alpheidae) from the Persian Gulf and Gulf of Oman, Iran
Authors: DEHGHANI AMIR , SARI ALIREZA , NADERLOO REZA
Published: January 2019

In the present study, shrimps belonging to the genus Alpheus from the Persian Gulf and Gulf of Oman are documented based on the existing literature and extensive new sampling from 2013 to 2018 along the Iranian coast. A total of 35 species are recorded from the region, of which 40% (14 species) and 60% (21 species) are new records for the Persian Gulf and Gulf of Oman, respectively. Among 19 sampling localities, A. lobidens De Haan, 1849, A. edwardsii (Audouin, 1826) and A. edamensis De Man, 1888 occurred in 14, 13 and 9 localities, respectively. Among the visited habitats, 14 species (40%) were associated with coral or other sessile invertebrates, 13 species (37%) were collected on sandy or rocky substrates, five species (14%) were obtained from muddy substrates, and three species (9%) were found associated with goby fishes. Among Alpheus species, three (10%) were endemic to the Persian Gulf. Most taxa show affinities to both western Indian Ocean and East Indian/West Pacific Oceans.
Revision of the Afrotropical flea beetle subgenus Blepharidina s. str. Bechyné (Coleoptera, Chrysomelidae)
Authors: D’ALESSANDRO PAOLA , IANNELLA MATTIA , BIONDI MAURIZIO
Published: January 2019

A taxonomic revision of the species attributed to the flea beetle subgenus Blepharidina s. str. Bechyné, 1968 from sub-Saharan Africa is provided. The subgenus comprises 20 species, including the following six new species here described: B. aliquantula sp. nov. from Somalia, B. himba sp. nov. from Namibia, B. kasigauensis sp. nov., B. kenyana sp. nov., B. regalini sp. nov. from Kenya, and B. matabelelandensis sp. nov. from Zimbabwe. A key to all the species is given, with photos of their habitus, aedeagus, spermatheca, and main external diagnostic characters. Taxonomic notes, with considerations on similarities and affinities, and ecological data on the habitat preference for each species, are also reported.
Three new species of the genus Choeras Mason, 1981 (Hymenoptera: Braconidae, Microgastrinae) from Iran
Authors: ABDOLI PARISA , TALEBI ALI ASGHAR , FARAHANI SAMIRA , FERNANDEZ-TRIANA JOSE
Published: January 2019

The genus Choeras Mason, 1981 (Hymenoptera: Braconidae, Microgastrinae) in northern Iran is studied taxonomically. Specimens were collected using Malaise traps during 2010 and 2011. A total of five species were identified, three being new species which are described and illustrated: Choeras formosus Abdoli & Fernandez-Triana sp. nov., C. fulviventris Fernandez-Triana & Abdoli sp. nov. and C. qazviniensis Fernandez-Triana & Talebi sp. nov. Two species (i.e., C. taftanensis and C. tiro) are new provincial records. The number of Choeras species in Iran is now raised to seven. An identification key to all West Palaearctic species of Choeras is provided.
What Is the Predictability Limit of Midlatitude Weather?
Authors: Zhang Fuqing , Sun Y. Qiang , Magnusson Linus , Buizza Roberto , Lin Shian-Jiann , Chen Jan-Huey , Emanuel Kerry
Published: January 2019

Understanding the predictability limit of day-to-day weather phenomena such as midlatitude winter storms and summer monsoonal rainstorms is crucial to numerical weather prediction (NWP). This predictability limit is studied using unprecedented high-resolution global models with ensemble experiments of the European Centre for Medium-Range Weather Forecasts (ECMWF; 9-km operational model) and identical-twin experiments of the U.S. Next-Generation Global Prediction System (NGGPS; 3 km). Results suggest that the predictability limit for midlatitude weather may indeed exist and is intrinsic to the underlying dynamical system and instabilities even if the forecast model and the initial conditions are nearly perfect. Currently, a skillful forecast lead time of midlatitude instantaneous weather is around 10 days, which serves as the practical predictability limit. Reducing the current-day initial-condition uncertainty by an order of magnitude extends the deterministic forecast lead times of day-to-day weather by up to 5 days, with much less scope for improving prediction of small-scale phenomena like thunderstorms. Achieving this additional predictability limit can have enormous socioeconomic benefits but requires coordinated efforts by the entire community to design better numerical weather models, to improve observations, and to make better use of observations with advanced data assimilation and computing techniques.
An Alternative Bias Correction Scheme for CrIS Data Assimilation in a Regional Model
Authors: Li Xin , Zou Xiaolei , Zeng Mingjian
Published: January 2019

Bias correction (BC) is a crucial step for satellite radiance data assimilation (DA). In this study, the traditional airmass BC scheme in the National Centers for Environmental Prediction (NCEP) Gridpoint Statistical Interpolation (GSI) is investigated for Cross-track Infrared Sounder (CrIS) DA. The ability of the airmass predictors to model CrIS biases is diagnosed. Correlations between CrIS observation-minus-background ( O − B) samples and the two lapse rate–related airmass predictors employed by GSI are found to be very weak, indicating that the bias correction contributed by the airmass BC scheme is small. A modified BC scheme, which directly calculates the moving average of O − B departures from data of the previous 2 weeks with respect to scan position and latitudinal band, is proposed and tested. The impact of the modified BC scheme on CrIS radiance DA is compared with the variational airmass BC scheme. Results from 1-month analysis/forecast experiments show that the modified BC scheme removes nearly all scan-dependent and latitude-dependent biases, while residual biases are still found in some channels when the airmass BC scheme is applied. Smaller predicted root-mean-square errors of temperature and specific humidity and higher equivalent threat scores are obtained by the DA experiment using the modified BC scheme. If O − B samples are replaced by observation-minus-analysis ( O − A) samples for bias estimates in the modified BC scheme, the forecast impacts are reduced but remain positive. A convective precipitation case that occurred on 21 August 2016 is investigated. Using the modified BC scheme, the atmospheric temperature structure and the geopotential height structures near trough/ridge areas are better resolved, resulting in better precipitation forecasts.
We’ve to Build the Pipeline. What’s the Problem? What’s Next? The Remix
Authors: Sharpe Rhonda Vonshay
Published: January 2019

Despite a history of initiatives to strengthen the doctorate pipeline and mentoring programs for graduate students and junior faculty, the economics profession has failed to achieve a representative level of diversity across ethnicity, gender and race. This National Economic Association presidential address looks at the 20-year production, 1996-2015, of economists by ethnicity, gender, race, and residential status with an interest in the production of Black economists. The findings suggest there is cause for alarm as the number of undergraduate economics degrees conferred to Black women was stagnant, and there has been a decrease in the number of doctorates conferred to Blacks men. In addition, the number of undergraduate mathematics degrees conferred to Blacks has decreased, which may have dire consequences for the economics and mathematics doctorate pipeline. Recommendations that promote the professional lives of Black and minority economists are provided.
Unequal urban rights: Critical reflections on property and urban citizenship
Authors: Brøgger Ditte
Published: January 2019

In the fast-growing cities of the Global South, urban forms of citizenship and urban rights are unequally defined and locally negotiated. The aim of this paper is to add the themes of property, landownership and housing as perspectives in the understanding of urban citizenship and to demonstrate how the urban is an arena for the negotiation of rights. This is done by examining urban citizenship and the graduated system of locally negotiated rights, including the right to property, the right to belong to an urban community and the right to urban resources. The research is located geographically in Nepal, where a typology of different classes of citizenship is developed in order to explain how classes of urban citizenship have different rights in the urban. Central to this is an analysis of unequal rights and unequal access to essential urban resources and services. The paper finds that the definition of (new) classes of urban citizenship in Nepal is critically embedded in historical practices and social structures. This demonstrates the relevance of further research into exclusionary practices in urban areas in the rapidly urbanising Global South and adds to the discussion of different types of urban citizenship and unequal rights to the urban space.