bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Small-Molecule Inhibitor of MRCK Prevents Radiation-Driven Invasion in Glioblastoma
Authors: Birch Joanna L. , Strathdee Karen , Gilmour Lesley , Vallatos Antoine , McDonald Laura , Kouzeli Ariadni , Vasan Richa , Qaisi Abdulrahman Hussain , Croft Daniel R. , Crighton Diane , Gill Kathryn , Gray Christopher H. , Konczal Jennifer , Mezna Mokdad , McArthur Duncan , Schüttelkopf Alexander W. , McConnell Patricia , Sime Mairi , Holmes William M. , Bower Justin , McKinnon Heather J. , Drysdale Martin , Olson Michael F. , Chalmers Anthony J.
Published: October 2018

Glioblastoma (GBM) is an aggressive and incurable primary brain tumor that causes severe neurologic, cognitive, and psychologic symptoms. Symptoms are caused and exacerbated by the infiltrative properties of GBM cells, which enable them to pervade the healthy brain and disrupt normal function. Recent research has indicated that although radiotherapy (RT) remains the most effective component of multimodality therapy for patients with GBM, it can provoke a more infiltrative phenotype in GBM cells that survive treatment. Here, we demonstrate an essential role of the actin-myosin regulatory kinase myotonic dystrophy kinase-related CDC42-binding kinase (MRCK) in mediating the proinvasive effects of radiation. MRCK-mediated invasion occurred via downstream signaling to effector molecules MYPT1 and MLC2. MRCK was activated by clinically relevant doses per fraction of radiation, and this activation was concomitant with an increase in GBM cell motility and invasion. Furthermore, ablation of MRCK activity either by RNAi or by inhibition with the novel small-molecule inhibitor BDP-9066 prevented radiation-driven increases in motility both in vitro and in a clinically relevant orthotopic xenograft model of GBM. Crucially, treatment with BDP-9066 in combination with RT significantly increased survival in this model and markedly reduced infiltration of the contralateral cerebral hemisphere.

Significance: An effective new strategy for the treatment of glioblastoma uses a novel, anti-invasive chemotherapeutic to prevent infiltration of the normal brain by glioblastoma cells.Cancer Res; 78(22); 6509–22. ©2018 AACR.
HERC2 Facilitates BLM and WRN Helicase Complex Interaction with RPA to Suppress G-Quadruplex DNA
Authors: Wu Wenwen , Rokutanda Nana , Takeuchi Jun , Lai Yongqiang , Maruyama Reo , Togashi Yukiko , Nishikawa Hiroyuki , Arai Naoko , Miyoshi Yasuo , Suzuki Nao , Saeki Yasushi , Tanaka Keiji , Ohta Tomohiko
Published: October 2018

BLM and WRN are RecQ DNA helicasesessential for genomic stability. Here, we demonstrate that HERC2, a HECT E3 ligase, is critical for their functions to suppress G-quadruplex (G4) DNA. HERC2 interacted with BLM, WRN, and replication protein A (RPA) complexes during the S-phase of the cell cycle. Depletion of HERC2 dissociated RPA from BLM and WRN complexes and significantly increased G4 formation. Triple depletion revealed that HERC2 has an epistatic relationship with BLM and WRN in their G4-suppressing function. In vitro, HERC2 released RPA onto single-stranded DNA (ssDNA) rather than anchoring onto RPA-coated ssDNA. CRISPR/Cas9-mediated deletion of the catalytic ubiquitin-binding site of HERC2 inhibited ubiquitination of RPA2, caused RPA accumulation in the helicase complexes, and increased G4, indicating an essential role for E3 activity in the suppression of G4. Both depletion of HERC2 and inactivation of E3 sensitized cells to the G4-interacting compounds telomestatin and pyridostatin. Overall, these results indicate that HERC2 is a master regulator of G4 suppression that affects the sensitivity of cells to G4 stabilizers. Given that HERC2 expression is frequently reduced in many types of cancers, G4 accumulation as a result of HERC2 deficiency may provide a therapeutic target for G4 stabilizers.

Significance: HERC2 is revealed as a master regulator of G-quadruplex, a DNA secondary structure that triggers genomic instability and may serve as a potential molecular target in cancer therapy.

Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/22/6371/F1.large.jpg. Cancer Res; 78(22); 6371–85. ©2018 AACR.
Gene Expression Profiling Reveals Aberrant T-cell Marker Expression on Tumor Cells of Waldenström's Macroglobulinemia
Authors: Hao Mu , Barlogie Bart , Tricot Guido , Liu Lanting , Qiu Lugui , Shaughnessy John D. , Zhan Fenghuang
Published: October 2018

Purpose:

That the malignant clone of Waldenström's macroglobulinemia (WM) demonstrates significant intraclonal heterogeneity with respect to plasmacytoid differentiation indicates the mechanistic complexity of tumorigenesis and progression. Identification of WM genes by comparing different stages of B cells may provide novel druggable targets.

Experimental Design:

The gene expression signatures of CD19+ B cells (BC) and CD138+ plasma cells (PC) from 19 patients with WM were compared with those of BCs from peripheral blood and tonsil and to those of PCs from the marrow of healthy (N-PC) and multiple myeloma donors (MM-PC), as well as tonsil (T-PC). Flow cytometry and immunofluorescence were used to examine T-cell marker expression on WM tumor cells.

Results:

Consistent with defective differentiation, both BCs and PCs from WM cases expressed abnormal differentiation markers. Sets of 55 and 46 genes were differentially expressed in WM-BC and WM-PC, respectively; and 40 genes uniquely dysregulated in WM samples were identified. Dysregulated genes included cytokines, growth factor receptors, and oncogenes not previously implicated in WM or other plasma cell dyscrasias. Interestingly, strong upregulation of both IL6 and IL6R was confirmed. Supervised cluster analysis of PC revealed that marrow-derived WM-PC was either MM-PC–like or T-PC–like, but not N-PC–like. The aberrant expression of T-cell markers was confirmed at the protein level in WM-BC.

Conclusions:

We showed that comparative microarray profiles allowed gaining more comprehensive insights into the biology of WM. The data presented here have implications for the development of novel therapies, such as targeting aberrant T-cell markers in WM.
Fusion Kinases Identified by Genomic Analyses of Sporadic Microsatellite Instability–High Colorectal Cancers
Authors: Sato Kazuhito , Kawazu Masahito , Yamamoto Yoko , Ueno Toshihide , Kojima Shinya , Nagae Genta , Abe Hiroyuki , Soda Manabu , Oga Takafumi , Kohsaka Shinji , Sai Eirin , Yamashita Yoshihiro , Iinuma Hisae , Fukayama Masashi , Aburatani Hiroyuki , Watanabe Toshiaki , Mano Hiroyuki
Published: October 2018

Purpose:

Colorectal cancers with microsatellite instability–high (MSI-H) status, due to mismatch repair deficiency, are associated with poor patient outcomes after relapse. We aimed to identify novel therapeutic targets for them.

Experimental Design:

We performed MSI analyses of over 2,800 surgically resected colorectal tumors obtained from consecutive patients treated in Japan from 1998 through June 2016. Whole-exome sequencing, transcriptome sequencing, and methylation analyses were performed on 149 of 162 tumors showing MSI in BAT25 and BAT26 loci. We analyzed patient survival times using Bonferroni-adjusted log-rank tests.

Results:

Sporadic MSI-H colorectal cancers with promoter methylation of MLH1 (called MM) had a clinicopathological profile that was distinct from that of colorectal cancers of patients with germline mutations (Lynch syndrome, LS-associated) or somatic, Lynch-like mutations in mismatch repair genes. MM tumors had more insertions and deletions and more recurrent mutations in BRAF and RNF43 than LS-associated or Lynch-like MSI-H tumors. Eleven fusion kinases were exclusively detected in MM MSI-H colorectal cancers lacking oncogenic KRAS/BRAF missense mutations and were associated with worse post-relapse prognosis. We developed a simple method to identify MM tumors and applied it to a validation cohort of 28 MSI-H colorectal cancers, identifying 16 MM tumors and 2 fusion kinases.

Conclusions:

We discovered that fusion kinases are frequently observed among sporadic MM MSI-H colorectal cancers. The new method to identify MM tumors enables us to straightforwardly group MSI-H patients into candidates of LS or fusion kinase carriers.
Arming an Oncolytic Herpes Simplex Virus Type 1 with a Single-chain Fragment Variable Antibody against PD-1 for Experimental Glioblastoma Therapy
Authors: Passaro Carmela , Alayo Quazim , DeLaura Isabel , McNulty John , Grauwet Korneel , Ito Hirotaka , Bhaskaran Vivek , Mineo Marco , Lawler Sean E. , Shah Khalid , Speranza Maria C. , Goins William , McLaughlin Eric , Fernandez Soledad , Reardon David A. , Freeman Gordon J. , Chiocca E. Antonio , Nakashima Hiroshi
Published: October 2018

Purpose:

Glioblastoma (GBM) is resistant to standard of care. Immune checkpoints inhibitors (such as anti-PD-1 mAbs) efficiently restore antitumor T-cell activity. We engineered a new oncolytic herpes simplex virus (oHSV) expressing a single-chain antibody against PD-1 (scFvPD-1) to evaluate its efficacy in mouse models of GBM.

Experimental Design:

NG34scFvPD-1 expresses the human GADD34 gene transcriptionally controlled by the Nestin promoter to allow replication in GBM cells and a scFvPD-1 cDNA transcriptionally controlled by the CMV promoter. ELISA assays were performed to detect binding of scFvPD-1 to mouse and human PD-1. In vitro cytotoxicity and replication assays were performed to measure NG34scFvPD-1 oncolysis, and scFvPD-1 expression and secretion were determined. In vivo survival studies using orthotopic mouse GBM models were performed to evaluate the therapeutic potency of NG34scFvPD-1.

Results:

NG34scFvPD-1–infected GBM cells express and secrete scFvPD-1 that binds mouse PD-1. The introduction of the scFvPD-1 sequence in the viral backbone does not alter the oncolytic properties of NG34scFvPD-1. In situ NG34scFvPD-1 treatment improved the survival with a tail of durable survivorship in 2 syngeneic immunocompetent mouse models of GBM. Mice that survived the first GBM challenge rejected the second challenge of GBM when implanted in the contralateral hemisphere. However, this was not true when athymic mice were employed as the recipients of the second challenge, consistent with the need for an intact immune system to obtain a memory response.

Conclusions:

NG34scFvPD-1 treatment induces a durable antitumor response in 2 preclinical mouse models of GBM with evidence for antitumor memory.
Predictive Biomarkers for Checkpoint Immunotherapy: Current Status and Challenges for Clinical Application
Authors: Tray Nancy , Weber Jeffrey S. , Adams Sylvia
Published: October 2018

Immune-checkpoint blockade (ICB), in particular PD-1 inhibition, has rapidly changed the treatment landscape and altered therapeutic paradigms across many tumor types, with unprecedented rates of durable clinical responses in a number of cancers. Despite this success, only a subset of patients responds to ICB and, as a result, predictive biomarkers would be useful to guide the selection of patients for these therapies. This article highlights currently used biomarkers, as well as several promising novel candidates, and also discusses the challenges involved in establishing their analytic validity and clinical utility. Progress is being evaluated in melanoma and non–small cell lung cancer, for which PD-1 ± CTLA-4 inhibitors have become standard therapy, to other malignancies for which PD-L1 inhibitors remain investigational. Although single biomarkers have substantial limitations, a combination of biomarkers that reflect the interaction of host and tumor will likely be needed to provide a reproducible surrogate for the benefit of checkpoint modulation. Cancer Immunol Res; 6(10); 1122–8. ©2018 AACR.
Laitinen’s Subgenual Cingulotomy: Anatomical Location and Case Report
Authors: Huotarinen Antti , Kivisaari Riku , Hariz Marwan
Published: October 2018

Background: The widespread use of deep brain stimulation (DBS) for movement disorders has renewed the interest in DBS for psychiatric disorders. Lauri Laitinen was a pioneer of stereotactic psychosurgery in the 1950s to 1970s, especially by introducing the subgenual cingulotomy. Our aim here was to verify the anatomical target used by Laitinen, to report on a patient who underwent this procedure, and to review the literature. Materials and Methods: The records of Helsinki University Hospital were searched for psychosurgical cases performed between 1970 and 1974. Alive consenting patients were interviewed and underwent a brain MRI. Results: We found 1 patient alive who underwent subgenual cingulotomy in 1971 for obsessive thoughts, anxiety, and compulsions, diagnosed at that time as “schizophrenia psychoneurotica.” MRI showed bilateral subgenual cingulotomy lesions (254 and 160 mm3, respectively). The coordinates of the center of the lesions in relation to the midcommissural point for the right and left, respectively, were: 7.1 and 7.9 mm lateral; 0.2 mm inferior and 1.4 mm superior, and 33.0 and 33.9 anterior, confirming correct subgenual targeting. The patient reported retrospective satisfactory results. Conclusions: The lesion in this patient was found to be in the expected location, which gives some verification of the correct placement of Laitinen’s subgenus cingulotomy target.
Thermal Response of Epigenetic Genes Informs Turtle Sex Determination with and without Sex Chromosomes
Authors: Radhakrishnan Srihari , Literman Robert , Neuwald Jennifer L. , Valenzuela Nicole
Published: October 2018

Vertebrate sexual fate can be established by environmental cues (e.g., temperature-dependent sex determination, TSD) or by genetic content (genotypic sex determination, GSD). While methylation is implicated in TSD, the influence of broader epigenetic processes in sexual development remains obscure. Here, we investigated for the first time the embryonic gonadal expression of the genome-wide epigenetic machinery in turtles, including genes and noncoding RNAs (ncRNAs) involved in DNA/histone acetylation, methylation, ubiquitination, phosphorylation, and RNAi. This machinery was active and differentially thermosensitive in TSD versus GSD (ZZ/ZW) turtles. Methylation and histone acetylation genes responded the strongest. The results suggest these working hypotheses: (i) TSD might be mediated by epigenetically controlled hormonal pathways (via acetylation, methylation, and ncRNAs), or by (ii) hormonally controlled epigenetic processes, and (iii) key epigenetic events prior to the canonical thermosensitive period may explain differences between TSD and GSD. Novel epigenetic candidate regulators other than methylation were identified, including previously unknown ncRNAs that could potentially mediate gonadogenesis. These findings illuminate the molecular ecology of reptilian sex determination and permitted hypothesis building to help guide future functional studies on the epigenetic transduction of external cues in TSD versus GSD systems.
Resistance to Fas-Mediated Apoptosis Does Not Correlate to Structural Alterations or Expression Changes of the Death Receptor in Papillary Thyroid Carcinomas
Authors:   Fanourakis, Saetta Angelica A. , Lazaris Andreas C. , Miaouli Maria , Voutsinas Gerassimos E. , Patsouris Efstratios , Tseleni-Balafouta Sofia
Published: October 2018

Background: Malignant cells exhibit significant resistance to FAS-mediated cell death, through different processes, including FAS mutations, soluble FAS expression, or FAS transcriptional dysregulation by P53, eventually escaping from immune surveillance. Since thyroid carcinomas were shown to be resistant to FAS-mediated apoptosis, we investigated the above mechanisms in thyroid carcinoma samples. Methods: Thirty-seven thyroid carcinoma samples were analyzed for mutations in FAS exon 9 and TP53 exons 5–8 and protein expression by means of immunohistochemistry. Moreover, thyroid carcinoma mRNA samples were subjected to reverse transcription – PCR, to evaluate the relative expression of transmembrane FAS versus its soluble form. Results: Analysis revealed indications for TP53 mutations in the anaplastic carcinomas, but not in the other thyroid specimens examined for TP53 or FAS exon 9 mutations. FAS receptor expression was observed in almost all thyroid specimens (97%) with significant up-regulation in papillary carcinomas. P53 nuclear staining was observed only in anaplastic carcinomas. Full-length FAS mRNA was detected in all specimens examined, with soluble FAS mRNA being either absent or present in very low amounts. Conclusions: Our results denote that FAS death domain or TP53 DNA-binding domain mutations, down-regulation of FAS receptor expression, or expression of FAS soluble isoform are not responsible for the seeming inhibition of FAS-mediated apoptosis in papillary thyroid carcinoma cells.
Alveolar Echinococcosis Mimicking a Hepatic Neoplasm with Lymph Node Metastasis: A Case Report
Authors: Amano Takahiro , Hayashi Shiro , Nishida Tsutomu , Matsubara Tokuhiro , Takahashi Kei , Nakamatsu Dai , Tomimaru Yoshito , Yamamoto Masashi , Nakajima Sachiko , Fukui Koji , Tamura Hiromi , Adachi Shiro , Dono Keizo , Inada Masami
Published: October 2018

A 37-year-old man had an asymptomatic 17-mm mass in the liver by health check with ultrasonography. Five years later, he was referred to our hospital because the mass was slightly enlarged with a peripancreatic lymph node. We performed endoscopic ultrasonography fine-needle aspiration (EUS-FNA) to evaluate a lymph node, but it showed amorphous eosinophilic material and eosinophilic infiltrate in necrotic tissue of toothpaste-like white specimen. However, we diagnosed as potentially malignant liver mass with lymph node metastasis because of 2-deoxy-2-(fluorine-18) fluorodeoxyglucose uptake. We then performed hepatectomy and enucleation of the pancreas. DNA polymerase chain reaction analysis revealed Echinococcus multilocularis infection. Retrospectively, we could find a part of Echinococcus in the specimens of EUS-FNA.
Association of Environmental Tobacco Smoke with the Risk of Severe Early Childhood Caries among 3-Year-Old Japanese Children
Authors: Nakayama Yoshimi , Ohnishi Hirofumi , Mori Mitsuru
Published: October 2018

Severe early childhood caries (S-ECC) has serious consequences for primary dentition, affecting the overall health, well-being, and quality of life of the child. The aim of this study was to investigate the association of risk factors, including environmental tobacco smoke (ETS), with S-ECC in 3-year-old Japanese children by a cross-sectional study. Study subjects were 2,825 children aged 3 years old. Of these individuals, after excluding the study subjects with missing values, a total of 2,277 children were included in the present analysis. The self-administered questionnaire included such items as sex, whether a smoker resides in the home, the number of smokers in the home, snack time, drinking or eating sweets after dinner, frequency of parents brushing their child’s teeth, the use of fluoride toothpaste, and socioeconomic status. We obtained the number of decayed, missing, or filled teeth per person (dmft) from dental examinations. Logistic regression analysis was performed to estimate the odds ratio for S-ECC. The average number of decayed, missing, and filled teeth (dmft index) was 0.77. The prevalence of dental caries was 20.6%. There was at least 1 smoker in the homes of 1,370 subjects (60.2%). After excluding items of multicollinearity, the results of multivariate analysis were as follows: drinking or eating sweets after dinner, irregular snack times, parents brushing their child’s teeth less frequently, existence of smokers in the home, and no residence tax were significantly associated with S-ECC. This study suggests that there is a significant association between ETS from family members and S-ECC.
Schema Modes and Personality Disorder Symptoms in Alcohol-Dependent and Cocaine-Dependent Patients
Authors: Boog Michiel , van Hest Klaartje M. , Drescher Tamar , Verschuur Margot J. , Franken Ingmar H.A.
Published: October 2018

Substance use disorders (SUD) and personality disorders co-occur frequently. This relationship might be understood by studying schema modes (a key concept in Schema therapy), which explain the dysfunctions characterizing personality disorder patients. In the present study, we compared the schema modes and personality disorder symptoms between alcohol-dependent patients, cocaine-dependent patients and healthy controls. We found indications that specific schema modes are specific for SUD patients. However, no differences between specific subtypes of SUD patients (alcohol- vs. cocaine-dependent patients) could be found regarding schema modes. Further, it is suggested that borderline personality disorder symptoms are highly relevant for SUD patients. A first step is made in understanding the relationship between schema modes and SUD, which may contribute to the understanding of the problematic behaviour seen in patients with personality disorders and SUD (and may possibly contribute to the improvement of the treatment of this group of patients).
Overcoming Drug Resistance in Colon Cancer by Aptamer-Mediated Targeted Co-Delivery of Drug and siRNA Using Grapefruit-Derived Nanovectors
Authors: Yan Wei , Tao Mingyue , Jiang Baofei , Yao Mengchu , Jun Yali , Dai Weijie , Tang Zhuang , Gao Yong , Zhang Li , Chen Xiaofei , Wang Qi-long
Published: October 2018

Background/Aims: Multidrug resistance (MDR) is the most common cause of chemotherapy failure. Upregulation of P-glycoprotein (P-gp) is one of the main mechanisms underlying MDR. Methods: In this study, we developed a targeted drug and small interfering (si)RNA co-delivery system based on specific aptamer-conjugated grapefruit-derived nanovectors (GNVs) that we tested in MDR LoVo colon cancer cells. The internalization of nanovectors in cancer cells was tested by fluorescence microscopy and flow cytometry. The anti-cancer activity in vitro was determined by colony formation and cell apoptosis assays. The biodistribution of nanovectors was analyzed by live imaging and the anti-cancer activity in vivo was observed. Results: GNVs loaded with aptamer increased doxorubicin (Dox) accumulation in MDR LoVo cells, an effect that was abolished by pretreatment with DNase. The LA1 aptamer effectively promoted nanovector internalization into cells at 4°C and increased the targeted delivery of Dox to tumors. Constructs harboring Dox, LA1, and P-gp siRNA more effectively inhibited proliferation and enhanced apoptosis in cultured MDR LoVo cells while exhibiting more potent anti-tumor activity in vivo than free Dox or GNVs loaded with Dox alone or in conjunction with LA1, an effect that was associated with downregulation of P-gp expression. Conclusion: This GNV-based system may be an effective strategy for overcoming MDR in clinical settings.
Long Non-Coding MALAT1 Functions as a Competing Endogenous RNA to Regulate Vimentin Expression by Sponging miR-30a-5p in Hepatocellular Carcinoma
Authors: Pan Yujia , Tong Simeng , Cui Rongjun , Fan Jialin , Liu Chi , Lin Yucui , Tang Jiebing , Xie Hui , Lin Ping , Zheng Tianhu , Yu Xiaoguang
Published: October 2018

Background/Aims: Hepatocellular carcinoma (HCC) has a high morbidity as well as mortality and is believed to be one of the most prevalent cancers worldwide. The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in numerous cancers, including HCC. This study aimed to explore the role of MALAT1 in HCC progression. Methods: The expression levels of MALAT1 and Vimentin in HCC tissues and relative pair-matched adjacent normal liver tissues were analyzed by RT-PCR, and immunohistochemistry. Using bioinformatics analysis and dual-luciferase assay, we examined the correlation between MALAT1 and miR-30a-5p. Dual-luciferase assay and western blotting suggested that Vimentin was a target of miR-30a-5p. A wound healing assay and transwell assays were employed to determine the effect of MALAT1 and miR-30a-5p on cell migration and invasion in HCC. Results: Our data demonstrated that the levels of MALAT1 and Vimentin were upregulated in HCC tissues and that miR-30a-5p was a direct target of MALAT1. Silenced MALAT1 and overexpressed miR-30a-5p each inhibited cell migration and invasion. Additionally, dual-luciferase assay and western blotting demonstrated that MALAT1 could competitively sponge miR-30a-5p and thereby regulate Vimentin. Conclusion: Our data suggest that MALAT1 acts as an oncogenic lncRNA that promotes HCC migration and invasion. Therefore, the MALAT1-miR-30a-5p-Vimentin axis is a potential therapeutic target and molecular biomarker in HCC.
The Novel Effect of Immunomodulator-Glatiramer Acetate on Epileptogenesis and Epileptic Seizures
Authors: Lai Ming-Chi , Lin Kao-Min , Yeh Poh-Shiow , Wu Sheng-Nan , Huang Chin-Wei 
Published: October 2018

Background/Aims: Immunological mechanisms can be triggered as a response to central nervous system insults and can lead to seizures. In this study an investigation was made to determine if glatiramer acetate (GA), an immunomodulator currently used in the treatment of multiple sclerosis, could protect rats from pilocarpine-induced seizures and chronic epilepsy. Methods: Two groups of adult male Sprague-Dawley rats, experimental (GA) and control, were used in the study. The systemic IL-1α and IL-1β levels at baseline were checked as well as status epilepticus (SE), and the spontaneous recurrent seizure (SRS) stage by enzyme-linked immunosorbent assay. The GA group was given GA (150 μg/kg, ip) and the control group was given a saline injection prior to pilocarpine-induced seizures. Seizure susceptibility, severity and mortality were evaluated, using Racine seizure classification and hippocampal damage was evaluated by Nissl staining. The GA group received GA (150 μg/kg/day, ip) daily after SE, and the chronic spontaneous seizures were evaluated by long-term video recording, and mossy fiber sprouting was evaluated by Timm staining. The IL-1α and IL-1β levels were correlated with seizure activities. The TNF-α level in the hippocampus was determined at the SRS stage by immunohistochemistry. The effect of GA on ionic currents and action potentials (APs) in NG108-15 differentiated neurons was investigated using patch-clamp technology. Results: It was found that latency to severe seizures was significantly longer in the GA (p < 0.01) group, which also had SE of shorter duration and less frequent SRS (p < 0.01). GA attenuated acute hippocampal neuron loss and chronic mossy fiber sprouting in the CA3 and the SRS-reduction correlated with the reduction of IL-1α, but not with IL-1β or TNF-α levels. Mechanistically, GA reduced the peak amplitude of voltage-gated Na+ current (INa), with a negative shift in the inactivation curve of INa and reduced the amplitude of APs along with decreased firing of APs. Conclusion: GA might serve as a neuroexcitability modulator which attenuates pilocarpine-induced acute and chronic excitotoxicity. Sodium channel attenuation was partially independent of the immunomodulatory effect.
A Música e as Artes auxiliando o desenvolvimento humano
Authors: Lima Sonia Regina Albano de
Published: October 2018

São muitas as pesquisas que demonstram de que forma as Artes e o ensino artístico atuam no desenvolvimento psíquico, físico, sociocultural, mental e estético dos indivíduos. No que concerne ao cenário musical mais especificamente, pesquisas realizadas por A. Storr, J. Sloboda, H. Gardner, L. Meyer, entre outros, relatam o caráter ordenatório desta linguagem, a ligação que ela estabelece com o corpo humano, o seu efeito sensibilizador, a experiência emocional e estética que ela abriga. Esse trabalho investigativo traz para essa arte um sentido e função que transcende o caráter puramente estético que ela contempla, constituindo-se em uma linguagem integrada às demais linguagens, capaz de contribuir de forma benéfica na evolução integral dos indivíduos. Assim, a inclusão do ensino musical na educação básica, nos cursos de formação de docente e na educação informal sob diferentes propostas e condições torna-se uma medida salutar para a evolução humana.
The “Sole Legal Government of Vietnam”: The Bao Dai Factor and Soviet Attitudes toward Vietnam, 1947–1950
Authors: Szalontai Balázs
Published: October 2018

Earlier historical studies often suggested that the Soviet leader Iosif Stalin, distrustful as he was of Ho Chi Minh's policies and attributing little importance to Vietnam, remained unwilling to recognize the Democratic Republic of Vietnam until the Chinese Communist leaders threw their weight behind their Vietnamese comrades. On the basis of Soviet press articles, Hungarian archival documents, United Nations (UN) records, and other sources, this article shows that in fact Soviet interest in Vietnam significantly increased as early as 1948–1949, well before the proclamation of the People's Republic of China. This interest, expressed in growing press coverage and sporadic efforts to represent North Vietnam's cause in various UN organs, seems to have been linked to Moscow's strong disapproval of France's attempts to create an anti-Communist “puppet state.” From the outset, the USSR took the position that the Communist North was the sole legitimate representative of the Vietnamese nation and, hence, that the Bao Dai regime in the South was ipso facto illegitimate. The article concludes that Chinese support to Ho Chi Minh was only one of the three major factors that persuaded Stalin to recognize North Vietnam; the two others were the “Bao Dai factor” and Moscow's dissatisfaction with France's new European policy.
Building a Black Bridge: China's Interaction with African-American Activists during the Cold War
Authors: Li Hongshan
Published: October 2018

This article examines the interactions between the People's Republic of China (PRC) and African-American activists during the Cold War. Relying mostly on archival records and personal documents in English as well as Chinese, the article shows that the construction of the new “black bridge” was made possible because of the PRC's determination to achieve its policy objectives, the African-American activists' needs in fighting for racial equality, and the U.S. government's strict ban on travel to China. Both the PRC and the black activists were new to these transnational interactions, and they worked together in such an unprecedented manner that they redefined the nature and function of Sino-American cultural relations. The black bridge facilitated a limited flow of people and information but also carried misinformation that eventually led to greater misunderstanding and fiercer confrontation. The bridge began to fade in the late 1960s and early 1970s as Beijing was forced to readjust its policy toward the United States, which soon lifted its ban on travel to the PRC.
RFE/RL Broadcasting and West German Society: Caught between Nature Protection Activism and Anti-Americanism
Authors: Komska Yuliya
Published: October 2018

This article contributes to the historiography of two separate topics that became intertwined in the final decade of the Cold War: wildlife protection activism and Cold War broadcasting. The article explains how the activities of Radio Free Europe (RFE), a U.S.-funded radio station based in the Federal Republic of Germany (FRG) that transmitted shortwave broadcasts to five Soviet-bloc countries, throw into sharp relief the fine line between the advantages of radio technologies and their pitfalls. The article focuses on a protracted conflict between RFE and the FRG's bird protection activists in the 1980s and early 1990s. Some U.S. officials viewed the fight over the station's superior “killer technologies” as reflecting anti-Americanism during Ronald Reagan's presidency, but West German officials saw it more as an outgrowth of the species protection movement that had recently become a part of the FRG's political mainstream. The article highlights the complex social and international political dimensions of the dispute.
A new approach to concept basicness and stability as a window to the robustness of concept list rankings
Authors: Dellert Johannes , Buch Armin
Published: October 2018

Based on a recently published large-scale lexicostatistical database, we rank 1,016 concepts by their suitability for inclusion in Swadesh-style lists of basic stable concepts. For this, we define separate measures of basicness and stability. Basicness in the sense of morphological simplicity is measured based on information content, a generalization of word length which corrects for distorting effects of phoneme inventory sizes, phonotactics and non-stem morphemes in dictionary forms. Stability against replacement by semantic shift or borrowing is measured by sampling independent language pairs, and correlating the distances between the forms for the concept with the overall language distances. In order to determine the relative importance of basicness and stability, we optimize our combination of the two partial measures towards similarity with existing lists. A comparison with and among existing rankings suggests that concept rankings are highly data-dependent and therefore less well-grounded than previously assumed. To explore this issue, we evaluate the robustness of our ranking against language pair resampling, allowing us to assess how much volatility can be expected, and showing that only about half of the concepts on a list based on our ranking can safely be assumed to belong on the list independently of the data.
Linguistic diversification as a long-term effect of asymmetric priming
Authors: Baumann Andreas , Sommerer Lotte
Published: October 2018

This paper tries to narrow the gap between diachronic linguistics and research on population dynamics by presenting a mathematical model corroborating the notion that the cognitive mechanism of asymmetric priming can account for observable tendencies in language change. The asymmetric-priming hypothesis asserts that items with more substance are more likely to prime items with less substance than the reverse. Although these effects operate on a very short time scale (e.g. within an utterance) it has been argued that their long-term effect might be reductionist, unidirectional processes in language change. In this paper, we study a mathematical model of the interaction of linguistic items that differ in their formal substance, showing that, in addition to reductionist effects, asymmetric priming also results in diversification and stable coexistence of two formally related variants. The model will be applied to phenomena in the sublexical as well as the lexical domain.
Three tree priors and five datasets
Authors: Rama Taraka
Published: October 2018

The age of the root of the Indo-European language family has received much attention since the application of Bayesian phylogenetic methods by Gray and Atkinson (2003). With the application of new models, the root age of the Indo-European family has tended to decrease from an age that supported the Anatolian origin hypothesis to an age that supports the Steppe origin hypothesis (Chang et al., 2015). However, none of the published work in Indo-European phylogenetics has studied the effect of tree priors on phylogenetic analyses of the Indo-European family. In this paper, I intend to fill this gap by exploring the effect of tree priors on different aspects of the Indo-European family’s phylogenetic inference. I apply three tree priors—Uniform, Fossilized Birth-Death (FBD), and Coalescent—to five publicly available datasets of the Indo-European language family. I evaluate the posterior distribution of the trees from the Bayesian analysis using Bayes Factor, and find that there is support for the Steppe origin hypothesis in the case of two tree priors. I report the median and 95 % highest posterior density (HPD) interval of the root ages for all three tree priors. A model comparison suggests that either the Uniform prior or the FBD prior is more suitable than the Coalescent prior to the datasets belonging to the Indo-European language family.
Taxa related to Diplotaxis virgata (Brassicaceae) in northwest Africa
Authors: MARTÍNEZ-LABORDE JUAN B.
Published: October 2018

The taxonomy of North African Diplotaxis taxa related to D. virgata is addressed. On the basis of extensive morphological observations on dried and living material, the status of D. virgata f. sahariensis (from southern Morocco and northwestern Algeria) is raised to species level as D. sahariensis comb. et stat. nov., and that of D. catholica var. tenuirostris is changed to D. virgata subsp. tenuirostris stat. nov. A new species, Diplotaxis australis sp. nov., is described from southwestern Morocco. A key for the identification of species within the D. virgata-alliance is provided.
Three novel species of Bacillariophyta (Diatoms) in the genera Surirella and Thalassiosira from Pleistocene Paleolake Lorenyang (~2 - 1.6 Ma) Turkana Basin, Kenya
Authors: BRINDLE MATTHEW , MOHAN JOSEPH , BECK CATHERINE , STONE JEFFERY R.
Published: October 2018

Three novel species of Bacillariophyta (diatom) are described from the sediments of Paleolake Lorenyang, a large lake that existed in the Turkana Basin, Kenya during the Gelasian age of the Pleistocene Epoch. Sediment cores extracted as part of the Hominin Sites and Paleolakes Drilling Project (HSPDP) were sampled to provide a diatom-based paleoecological record of Paleolake Lorenyang. Preliminary results of the paleoecological analysis unearthed three novel species of diatoms belonging to Surirella and Thalassiosira in the Natoo Member of the Nachukui Formation. Comparisons of Surirella from Paleolake Lorenyang are made to previous reports of Surirella from modern lakes in East Africa and comparisons of Thalassiosira species from the paleolake are made to modern and fossil species reported from East Africa. This is a first report of diatoms in the Natoo Member, which has previously been described as a floodplain deposit, and thus provides evidence of the last occurrence of Paleolake Lorenyang within the Turkana Basin. Herein we describe a new species of Surirella and two Thalassiosira with remarks on morphology and evolution of East African Surirella and Thalassiosira.
A monograph of the Afrotropical Cassidinae (Coleoptera: Chrysomelidae). Part 5. Revision of the genus Aethiopocassis Spaeth
Authors: BOROWIEC LECH
Published: October 2018

The genus Aethiopocassis Spaeth, 1922 is revised and 31 species are recognized as valid, all distributed in Sub-Saharan Africa. Seven species are described as new: Aethiopocassis angulicollis sp. nov. (Tanzania), Aethiopocassis dewittei sp. nov. (Democratic Republic of Congo), Aethiopocassis garambana sp. nov. (Democratic Republic of Congo), Aethiopocassis guineensis sp. nov. (Guinea), Aethiopocassis huilaensis sp. nov. (Angola), Aethiopocassis longidoana sp. nov. (Tanzania), and Aethiopocassis transvaalensis sp. nov. (Republic of South Africa). The following new synonyms are proposed: Aethiopocassis fugax (Spaeth, 1906) = Cassida (Aethiopocassis) scita Spaeth, 1924 syn. nov.; Aethiopocassis gallarum (Spaeth, 1906) = Cassida deplanata Spaeth, 1906 syn. nov. = Cassida sjoestedti Spaeth, 1906 syn. nov. = Cassida (Aethiopocassis) burensis Spaeth, 1924 syn. nov.; Aethiopocassis pauli (Weise, 1898) = Cassida pauli var. deleta Weise, 1899 syn. nov. = Cassida (Aethiopocassis) alluaudi Spaeth, 1924 syn. nov.; Aethiopocassis silphoides (Spaeth, 1906) = Cassida (Aethiopocassis) silphoides ssp. katangana Spaeth, 1933 syn. nov.; Aethiopocassis suspiciosa (Weise, 1903) = Cassida suspiciosa var. connexa Weise, 1906 syn. nov. = Cassida suspiciosa ssp. picturata Spaeth, 1934 syn. nov. = Cassida manubialis Spaeth, 1906 syn. nov., = Cassida decipiens Spaeth, 1906 syn. nov. = Cassida (Aethiopocassis) maynei Spaeth, 1933 syn. nov. = Aethiopocassis suspiciosa ssp. flavofemorata Spaeth, 1934 syn. nov. = Aethiopocassis maynei ssp. biramosa Spaeth, 1934 syn. nov. Colour photos, including intraspecific variablity, a key to species and maps of distribution are given.
Global guide of the flat wasps (Hymenoptera, Bethylidae)
Authors: AZEVEDO CELSO O. , ALENCAR ISABEL D.C.C. , RAMOS MAGNO S. , BARBOSA DIEGO N. , COLOMBO WESLEY D. , VARGAS JUAN M. R. , LIM JONGOK
Published: October 2018

The flat wasp family Bethylidae Haliday lacks global scale literature on their alpha taxonomy. The only world revision for the family was by Kieffer in 1914 and is fully out of date and somewhat useless; the only catalog for the family was made by Gordh & Móczár in 1990 and does not include hundreds of changes made since then; and the most recent world genera keys were proposed by Terayama in 2003, but do not reflect the current knowledge we have for the family. Given this scenario, we present a global guide of Bethylidae with diagnoses, taxonomic evaluation, keys, and a checklist of all their extant genera and subfamilies. We visited the main collections around the world, analyzed about 2,000 holotypes, and examined at least 400,000 specimens. To eliminate homonymies, we add the prefix “neo” to the original specific epithet when possible. The family is now composed by 2,920 species allocated in 96 genera distributed in eight subfamilies: Bethylinae, Pristocerinae, Epyrinae, Mesitiinae, Scleroderminae, Lancepyrinae, Holopsenellinae and Protopristocerinae. The latter three are extinct. One new family-group synonym is proposed: Fushunochrysidae Hong syn. nov. of Bethylidae. Two incertae sedis genera are allocated into Bethylinae: Cretobethylellus Rasnytsyn and Omaloderus Walker. One new genus-group synonym is revalidated: Pristepyris Kieffer stat. rev. from Acrepyris Kieffer. Sixteen new genus-group synonyms are proposed: Fushunochrysites Hong syn. nov. and Sinibethylus Hong syn. nov. of Eupsenella Westwood; Messoria Meunier syn. nov. of Goniozus Förster; Acrepyris Kieffer syn. nov. of Pristepyris Kieffer; Apristocera Kieffer syn. nov. and Parapristocera Brues syn. nov. of Pristocera Klug; Usakosia Kieffer syn. nov. of Prosapenesia Kieffer; Isobrachium Förster syn. nov., Leptepyris Kieffer syn. nov., Neodisepyris Kurian syn. nov., Rhabdepyris Kieffer syn. nov. of Epyris Westwood; Codorcas Nagy syn. nov., Hamusmus Argaman syn. nov. and Ukayakos Argaman syn. nov. of Heterocoelia Dahlbom; Domonkos Argaman syn. nov. of Incertosulcus Móczár; Ateleopterus Förster syn. nov. of Sclerodermus Latreille. One new genus-group synonym is revalidated: Topcobius Nagy syn. rev. of Sulcomesitius Móczár. One new genus-group revalidation is proposed: Incertosulcus Móczár stat. rev. from Anaylax Móczár. The following species-group nomenclatural acts are established: 153 new or revalidated combinations, 16 new names to avoid secondary homonyms, 11 species with revalidated status, and one synonym. Keys to the subfamilies and genera are provided. The text is supported by 599 illustrations organized onto 92 plates.
The Influence of Topography on the Stability of the Norwegian Atlantic Current off Northern Norway
Authors: Ghaffari Peygham , Isachsen Pål Erik , Nøst Ole Anders , Weber Jan Erik
Published: October 2018

The steep continental slope off the Lofoten–Vesterålen islands of northern Norway appears to be the source of the most intense mesoscale eddy field in all of the Nordic Seas. Here we use linearized two-layer shallow-water equations to study the stability of the Norwegian Atlantic Current in this region. The study extends previous works that used linearized quasigeostrophic vertical mode equations to examine the effects of bottom topography on baroclinic instability here. We find evidence of baroclinic instability in the stacked shallow-water model but also of barotropic instability that is associated with the upper-layer lateral shear. The calculations give an indication that growth rates of barotropic instability may be comparable to or larger than those of baroclinic instability over the steepest parts of the continental slope.
Evaluation of the Team Workload Questionnaire (TWLQ) in a Team-Choice Task
Authors: Greenlee Eric T. , Funke Gregory J. , Rice Lindsay
Published: October 2018

Objective:

The present study was designed to evaluate the team workload questionnaire (TWLQ) in a task that was distinct from the task used to create it.

Background:

The TWLQ was created from workload ratings generated by members of athletic sports teams. Given that such teams represent only a portion of the diversity of operational teams, we aimed to assess the generalizability of the TWLQ.

Method:

The present study applied the TWLQ in a collaborative choice task (hiring decision) to determine whether the factor structure reported in the initial publication of the scale would generalize from the execution tasks it was developed from to a disparate team task focused on consensus building.

Results:

Confirmatory factor analysis indicated that the present data ( N = 144) were a poor fit for the three-factor structure of the TWLQ. Subsequent exploratory factor analysis revealed a much more interrelated model of team workload with no clear division between the three conceptual factors described in the original validation of the TWLQ.

Conclusion:

The factor structure of the TWLQ did not generalize to the present team-choice task.

Application:

Given that the duties of operational teams vary, it is critical that future research examine how the conceptual structure of team workload may be altered by task type.
Difficult texts: Genesis 2.18 and 2.24
Authors: Agana Agana-Nsiire
Published: October 2018

It has long been argued on the basis of Genesis 2.18 that marriage is incumbent on all adults. With ministers and lay persons in the church urging that ‘it is not good for man to be alone’, the unmarried are frequently looked upon with ridicule, suspicion and outright disdain. However, an exegetical analysis of Genesis 2.18 does not support the view that marriage is a universal imperative.
Neighbourhood effects and beyond: Explaining the paradoxes of inequality in the changing American metropolis
Authors: Sampson Robert J
Published: October 2018

American cities today are simultaneously the same and different from Wilson’s classic portrayal in The Truly Disadvantaged ([1987] 2012), first published over 30 years ago. Concentrated poverty and racial segregation endure, as do racial gaps in multiple aspects of wellbeing. But mass incarceration, the dramatic drop in violent crime, immigration, rising income segregation, the suburbanisation of poverty, and other macrosocial trends have transformed the urban scene. The paradoxical result is that cities today are both better and worse off. In this paper, I put forth a unifying framework on persistence and change in urban inequality, highlighting a theory of neighbourhood effects and the higher-order structure of the contemporary metropolis. I apply this analytic framework to examine: (1) neighbourhood inequality as an important driver and mediator of urban transformation; (2) racial disparities across the life course in compounded deprivation, poisoned development, and intergenerational mobility; and (3) how everyday spatial mobility beyond the local neighbourhood is producing new forms of social isolation and higher-order segregation. I conclude with a challenge to dominant policy perspectives on urban racial inequality.