bluuebunny/crossref_metadata_2025_split huggingface dataset:
DAL PLURALISMO POLARIZZATO AL PLURALISMO MODERATO. IL MODELLO DI SARTORI E LA TRANSIZIONE ITALIANA
Authors: Pappalardo Adriano 
Published: September 2018

IntroduzioneNegli anni novanta, l'Italia è entrata in un processo di transizione che è ormai divenuto oggetto di un'abbondante letteratura nazionale e straniera. Piuttosto ovviamente, la natura di tale transizione è ben diversa da quelle dei paesi postcomunisti e, come ha opportunamente sottolineato Pasquino (1994; 1995), poco comparabile con altri precedenti storici. Anche la Francia, che questo autore considera il miglior termine di confronto, lo è in realtà assai relativamente sotto una varietà di punti di vista. Mentre infatti la Quarta e, per lungo tempo, anche la Quinta Repubblica sono rimasti classici casi di pluralismo polarizzato (Sartori 1982, 256–262), l'Italia degli anni novanta non può più essere definita tale, e proprio per questo (o, almeno, anche per questo) si è avviata alla presente transizione. Come è noto, inoltre, le riforme golliste investirono essenzialmente le principali istituzioni politiche della repubblica, ma lasciarono inalterati il subsistema burocratico e la struttura (centralizzata) dello Stato, che sono, invece, componenti tutt'altro che secondarie per comprendere il decorso e gli eventuali sbocchi della crisi italiana. Ma, infine, tale crisi si intreccia anche al declino dello Stato sociale e interventista, coinvolgendo la ridefinizione dei confini fra politica ed economia e il ruolo delle grandi organizzazioni degli interessi, sindacati in testa. Come dire che, oltre al sistema politico-istituzionale ed alla pubblica amministrazione, le relazioni industriali e i loro attori pubblici e privati rappresentano una terza dimensione di cambiamento, che altrove è stata poco importante (Francia), ovvero incomparabilmente diversa (regimi postcomunisti).
ALLA RICERCA DELLA COLLEGIALITÀ Dl GOVERNO: I VERTICI Dl MAGGIORANZA DAL 1970 AL 1994
Authors: Criscitiello Annarita 
Published: September 2018

PremessaLe radici della debolezza del governo collegiale nell'Italia repubblicana sono state individuate nel modello costituzionale formale così come fu ideato dai padri fondatori. Ma anche nel fatto che i governi italiani, tranne qualche eccezione, sono sempre stati governi di coalizione, una condizione che necessariamente rende il processo decisionale collegiale molto più complicato e controverso (Pappalardo 1978; Bogdanor 1983; Pridham 1986; Budge e Keman 1990; Laver e Schofield 1990).
PERCHÉ È DIFFICILE COSTRUIRE LE ISTITUZIONI
Authors: Lanzara Giovan Francesco 
Published: September 2018

IntroduzioneLa costruzione di un'istituzione, qualsiasi cosa possa significare, è comunque un processo che implica la formazione di una struttura, o codice, o pattern regolato di comportamenti che acquista legittimità e «funziona» in un contesto sociale specifico, fino a diventare un elemento costitutivo della vita sociale, stabile e persistente nel corso del tempo. Tale struttura può essere in parte il risultato di un progetto deliberato, in parte l'esito non intenzionale dell'azione umana e dell'interazione sociale. Il più delle volte è congiuntamente l'uno e l'altro, in combinazioni variabili a seconda delle contingenze. Se la struttura «funziona», essa potrà autosostenersi e riprodursi nel tempo. Ma in caso di «fallimento», provocato da un rendimento scadente o dall'erosione di legittimità morale e politica, non necessariamente verrà rimpiazzata in modo rapido e completo. Più verosimilmente le sue componenti fondamentali, anche se obsolete, continueranno a sopravvivere per lungo tempo «come frammenti di rotte catene, pendenti dalle volte di vecchi edifici» (Tocqueville 1969), senza alcuna funzione specifica, o forse subiranno un lento processo di mutamento, assumendo gradualmente nuove funzioni e significati col passare del tempo.
I CONFLITTI POLITICI IN EUROPA: PERSISTENZA E MUTAMENTO
Authors: Mair Peter 
Published: September 2018

IntroduzioneMalgrado un trentennio di attente analisi condotte da studiosi provenienti da diversi campi disciplinari e una voluminosa letteratura dedicata alla comprensione e spesso alla verifica della cosiddetta «ipotesi del congelamento» (freezing hypothesis), su ciò che Lipset e Rokkan pensassero si fosse consolidato negli anni '20 permane ancora oggi non poca confusione.
Disturbed interhemispheric functional connectivity in visual pathway in individuals with unilateral retinal detachment: A resting state fMRI study
Authors: YUAN QING , KANG HONG-HUA , SHI WEN-QING , GONG YING-XIN , SU TING , ZHU PEI-WEN , MIN YOU-LAN , YE LEI , JIANG NAN , SHAO YI 
Published: September 2018

AbstractPrevious neuroimaging studies demonstrated that retinal detachment (RD) subjects were associated with abnormal spontaneous brain activities; however, whether the altered interhemispheric functional connectivity (FC) occurred in RD patients remains unknown. The current study tried to explore the alternations of interhemispheric FC of the whole brain in unilateral RD patients using the voxel-mirrored homotopic connectivity (VMHC) method and their connections to clinical features. Methods: We recruited 30 patients with RD (16 males and 14 females) and 30 healthy controls (HCs) (16 males and 14 females) whose age and sex were closely matched. All subjects underwent the rs-fMRI scans. The VMHC method was applied to directly assess the hemispheres’ functional interaction. The VMHC in these brain areas, which could be used as biomarkers to differentiate RD from HC, was identified by the receiver operating characteristic (ROC) curve analyses. The relations between these patients’ clinical features and their mean VMHC signal values in multiple brain regions were calculated by Pearson correlation analysis. Results: RD patients had significantly lower VMHC values than HCs in the bilateral occipital lobe (Brodmann areas, BA 18), bilateral superior temporal gyrus (BA 39), and bilateral cuneus (BA 19). Moreover, the mean VMHC signal values of the bilateral cuneus were in positive correlation with the duration of the RD (r = 0.446, P = 0.013). Conclusion: Our results provided an evidence of disturbed interhemispheric FC in the visual area occurred in RD patients, which might provide some useful information to understand the neural mechanism of RD patients with acute vision loss. Furthermore, the VMHC values might indicate the progress of the RD.
Importance of Hydrothermal Vents in Scavenging Removal of 230Th in the Nansen Basin
Authors: Valk O. , Rutgers van der Loeff M. M. , Geibert W. , Gdaniec S. , Rijkenberg M. J. A. , Moran S. B. , Lepore K. , Edwards R. L. , Lu Y. , Puigcorbé V. 
Published: September 2018

AbstractIn this study we present dissolved and particulate 230Th and 232Th results, as well as particulate 234Th data, obtained as part of the GEOTRACES central Arctic Ocean sections GN04 (2015) and IPY11 (2007). Samples were analyzed following GEOTRACES methods and compared to previous results from 1991. We observe significant decreases in 230Th concentrations in the deep waters of the Nansen Basin. We ascribe this nonsteady state removal process to a variable release and scavenging of trace metals near an ultraslow spreading ridge. This finding demonstrates that hydrothermal scavenging in the deep‐sea may vary on annual time scales and highlights the importance of repeated GEOTRACES sections.
O-GlcNAcylation on Rab3A attenuates its effects on mitochondrial oxidative phosphorylation and metastasis in hepatocellular carcinoma
Authors: Wu Weicheng , Zheng Xixi , Wang Jing , Yang Tianxiao , Dai Wenjuan , Song Shushu , Fang Lan , Wang Yilin , Gu Jianxin 
Published: September 2018

AbstractRab3A is a small Ras-like GTPase critical for membrane traffic. Although the functions of Rab3A have been reported in several cancers, the roles of Rab3A in hepatocellular carcinoma (HCC) have never been determined. To investigate the potential roles of Rab3A in HCC progression, we first determined Rab3A levels in HCC tissues and observed upregulated mRNA and protein levels of Rab3A in most tumor tissues. However, in vitro data showed that decreasing Rab3A in most HCC cell lines conferred no significant effects and overexpressing Rab3A in PLC/PRF/5 cells even inhibited migration and invasion. Meanwhile, the upregulation of Rab3A in HCC patients did not correlate with metastasis or overall survival of HCC patients. These contradict data suggested that Rab3A might act as metastatic suppressor and its effects might be attenuated in most HCC cells. Further experiments revealed that O-GlcNAcylation on Rab3A was key for attenuating Rab3A-mediated effects by regulating its GTP-binding activity, and verified the effects of Rab3A and its aberrant O-GlcNAcylation on HCC metastasis in vitro and in vivo. We also found that Rab3A and its O-GlcNAcylation had opposite roles in mitochondria oxidative phosphorylation (mtOXPHOS), and their functions on HCC metastasis were partially depended on their effects on metabolic reprogramming.
CPEB1 mediates hepatocellular carcinoma cancer stemness and chemoresistance
Authors: Xu Min , Fang Shiji , Song Jingjing , Chen Minjiang , Zhang Qianqian , Weng Qiaoyou , Fan Xiaoxi , Chen Weiqian , Wu Xulu , Wu Fazong , Tu Jianfei , Zhao Zhongwei , Ji Jiansong 
Published: September 2018

AbstractCancer stem cells (CSCs) are a subpopulation of cells within tumors that are believed to possess pluripotent properties and thought to be responsible for tumor initiation, progression, relapse and metastasis. Cytoplasmic polyadenylation element-binding protein 1 (CPEB1), a sequence-specific RNA-binding protein that regulates mRNA polyadenylation and translation, has been linked to cancer progression and metastasis. However, the involvement of CPEB1 in hepatocellular carcinoma (HCC) remains unclear. In this study, we have demonstrated that CPEB1 directly regulates sirtuin 1 (SIRT1) mRNA to mediate cancer stemness in HCC. Cancer stemness was analyzed by self-renewal ability, chemoresistance, metastasis, expression of stemness-related genes and CSC marker-positive cell populations. The results indicate that CPEB1 is downregulated in HCC. Overexpression of CPEB1 dramatically reduced HCC cell stemness, whereas silencing CPEB1 enhances it. Using site-directed mutagenesis, a luciferase reporter assay, and immunoprecipitation, we found that CPEB1 could directly target the 3′-UTR of SIRT1, control poly(A) tail length and suppress its translation to mediate cancer stemness in vitro and in vivo. Overall, our findings suggest that the negative regulation between CPEB1 and SIRT1 contributes to the suppression of cancer stemness in HCC. CPEB1 may have potential as a therapeutic target in HCC.
RETRACTED ARTICLE: miR-665 promotes hepatocellular carcinoma cell migration, invasion, and proliferation by decreasing Hippo signaling through targeting PTPRB
Authors: Hu Yuanchang , Yang Chao , Yang Shikun , Cheng Feng , Rao Jianhua , Wang Xuehao 
Published: September 2018

AbstractGrowing evidence suggests that aberrant microRNA (miRNA) expression contributes to hepatocellular carcinoma (HCC) development and progression. However, the potential role and mechanism of miR-665 in the progression of liver cancer remains largely unknown. Our current study showed that miR-665 expression was upregulated in HCC cells and tissues. High expression of miR-665 exhibited more severe tumor size, vascular invasion and Edmondson grading in HCC patients. Gain- or loss-of-function assays demonstrated that miR-665 promoted cell proliferation, migration, invasion, and the epithelial–mesenchymal transition (EMT) of HCC cells in vitro and in vivo. Tyrosine phosphatase receptor type B (PTPRB) was downregulated in HCC tissues, and was negatively correlated with miR-665 expression. Through western blotting and luciferase reporter assay, PTPRB was identified as a direct downstream target of miR-665. Restoration of PTPRB reverses the effects of miR-665 on HCC migration, invasion, and cell proliferation. A mechanistic study showed that PTPTRB mediated the functional role of miR-665 through regulation of the Hippo signaling pathway. In conclusion, our results suggested that miR-665 was a negative regulator of the PTPRB and could promote tumor proliferation and metastasis in HCC through decreasing Hippo signaling pathway activity, which can be a potential target for HCC treatment.
RB1CC1-enhanced autophagy facilitates PSCs activation and pancreatic fibrogenesis in chronic pancreatitis
Authors: Li Le , Wang Gang , Hu Ji-Sheng , Zhang Guang-Quan , Chen Hong-Ze , Yuan Yue , Li Yi-Long , Lv Xin-Jian , Tian Feng-Yu , Pan Shang-Ha , Bai Xue-Wei , Sun Bei 
Published: September 2018

AbstractChronic pancreatitis (CP) is described as a progressive fibro-inflammatory disorder of the exocrine disease, which eventually leads to damage of the gland. Excessive activation of pancreatic stellate cells (PSCs) is a critical participant in the initiation of CP. Autophagy is involved in multiple degeneration and inflammation in acute pancreatitis and CP. In our study, we report that retinoblastoma coiled coil protein 1 (RB1CC1) expression and the autophagic level are elevated in activated PSCs. RB1CC1 is positively correlated with pancreatic fibrogenesis in tissues and plasma of CP patients. Knockdown of RB1CC1 restrains alpha smooth muscle actin (α-SMA) and collagen expressions, and autophagy in activated PSCs in vitro. Furthermore, we show that RB1CC1 induces PSC activation via binding to ULK1 promoter and the direct interaction with ULK1 protein. These suppress ULK1 expression and its kinase activity. In mice, knockdown of RB1CC1 blocks autophagy and then inhibits the pancreatic duct ligation-induced pancreatic fibrosis. Consequently, our study highlights that RB1CC1-mediated autophagy is a key event for the activation of PSCs. Inhibition of RB1CC1 alleviates autophagy, which plays a critical role in anti-fibrotic activation in PSCs and CP progression. RB1CC1 could be a novel strategy for the treatment of pancreatic fibrosis.
MTP18 overexpression contributes to tumor growth and metastasis and associates with poor survival in hepatocellular carcinoma
Authors: Zhang Yu , Li Hui , Chang Hulin , Du Lixue , Hai Jun , Geng Xilin , Yan Xiang 
Published: September 2018

Abstract
Background
Human MTP18 (mitochondrial protein 18 kDa) is a novel nuclear-encoded mitochondrial membrane protein that is involved in controlling mitochondrial fission. Our bioinformatic analysis of TCGA data revealed an aberrant overexpression of MTP18 in hepatocellular carcinoma (HCC). We analyzed its biological effects and prognostic significance in this malignancy.

Methods
MTP18 expression was evaluated by qRT-PCR and western blot analysis in 20 paired tumor and peritumor tissues. Clinical impact of MTP18 overexpression was assessed in 156 patients with HCC. The effects of MTP18 knockdown or overexpression on cell growth and metastasis were determined by cell proliferation, colony formation, cell cycle, apoptosis, migration, and invasion assays. Furthermore, the underlying molecular mechanisms by which MTP18 overexpression promoted HCC cell growth and metastasis were explored.

Results
MTP18 was commonly overexpressed in HCC tissues mainly due to the downregulation of miR-125b, which significantly contributed to poor prognosis of HCC patients. Functional experiments revealed that MTP18 promoted both the growth and metastasis of HCC cells by inducing the progression of cell cycle, epithelial to mesenchymal transition (EMT) and production of MMP–9, and suppressing cell apoptosis. Mechanistically, increased mitochondrial fission and subsequent ROS production was found to be involved in the promotion of growth and metastasis by MTP18 in HCC cells.

Conclusions
MTP18 plays a pivotal oncogenic role in hepatocellular carcinogenesis; its overexpression may serve as a novel prognostic factor and a therapeutic target in HCC.
A structural investigation of NRZ mediated apoptosis regulation in zebrafish
Authors: Suraweera Chathura D. , Caria Sofia , Järvå Michael , Hinds Mark G. , Kvansakul Marc 
Published: September 2018

AbstractBcl-2 family proteins play a crucial role in regulating apoptosis, a process critical for development, eliminating damaged or infected cells, host-pathogen interactions and in disease. Dysregulation of Bcl-2 proteins elicits an expansive cell survival mechanism promoting cell migration, invasion and metastasis. Through a network of intra-family protein–protein interactions Bcl-2 family members regulate the release of cell death factors from mitochondria. NRZ is a novel zebrafish pro-survival Bcl-2 orthologue resident on mitochondria and the endoplasmic reticulum (ER). However, the mechanism of NRZ apoptosis inhibition has not yet been clarified. Here we examined the interactions of NRZ with pro-apoptotic members of the Bcl-2 family using a combination of isothermal calorimetry and mutational analysis of NRZ. We show that NRZ binds almost all zebrafish pro-apoptotic proteins and displays a broad range of affinities. Furthermore, we define the structural basis for apoptosis inhibition of NRZ by solving the crystal structure of both apo-NRZ and a holo form bound to a peptide spanning the binding motif of the pro-apoptotic zBad, a BH3-only protein orthologous to mammalian Bad. The crystal structure of NRZ revealed that it adopts the conserved Bcl-2 like fold observed for other cellular pro-survival Bcl-2 proteins and employs the canonical ligand binding groove to bind Bad BH3 peptide. NRZ engagement of Bad BH3 involves the canonical ionic interaction between NRZ R86 and Bad D104 and an additional ionic interaction between NRZ D79 and Bad R100, and substitution of either NRZ R86 or D79 to Ala reduces the binding to Bad BH3 tenfold or more. Our findings provide a detailed mechanistic understanding for NRZ mediated anti-apoptotic activity in zebrafish by revealing binding to both Bad and Noxa, suggesting that NRZ is likely to occupy a unique mechanistic role in zebrafish apoptosis regulation by acting as a highly promiscuous pro-apoptotic Bcl-2 binder.
Taurine attenuates arsenic-induced pyroptosis and nonalcoholic steatohepatitis by inhibiting the autophagic-inflammasomal pathway
Authors: Qiu Tianming , Pei Pei , Yao Xiaofeng , Jiang Liping , Wei Sen , Wang Zhidong , Bai Jie , Yang Guang , Gao Ni , Yang Lei , Qi Shuangyue , Yan Rushan , Liu Xiaofang , Sun Xiance 
Published: September 2018

AbstractArsenic exposure causes nonalcoholic steatohepatitis (NASH). Inflammation is a key contributor to the pathology of nonalcoholic fatty liver disease (NAFLD), including NASH. However, it is unclear how arsenic induces inflammation. In mouse livers, we show that arsenic trioxide (As2O3) induced NASH, increased autophagy and NLRP3 inflammasome activation, increased lipid accumulation, and resulted in dysregulation of lipid-related genes. Supplemented with taurine (Tau) attenuated the inflammation and autophagy caused by As2O3. In HepG2 cells, we found that As2O3-induced pyroptotic cell death was dependent upon the activation of NLRP3 inflammasome, which was CTSB-dependent. In addition, inhibiting autophagy alleviated the As2O3-induced increase of cytosolic CTSB expression and subsequent release of LDH, activation of the NLRP3 inflammasome, and pyroptosis. Moreover, we found that Tau alleviated As2O3-induced elevation of autophagy, CTSB expression, and activation of the NLRP3 inflammasome, and reduced the release of LDH, pyroptotic cell death, and inflammation. Interestingly, As2O3-induced lipid accumulation could not be alleviated by either inhibition of autophagy nor by inhibition of CTSB. Additionally, neither inhibition of the NLRP3 inflammasome or Tau treatment could alleviate lipid accumulation. These results demonstrated that As2O3-induced pyroptosis involves autophagy, CTSB, and the NLRP3 inflammasome cascade, and that Tau alleviates As2O3-induced liver inflammation by inhibiting the autophagic-CTSB-NLRP3 inflammasomal pathway rather than decreasing lipid accumulation. These findings give insight into the association of autophagy, inflammation, pyroptosis, and NASH induced by As2O3.
A miR-125b/CSF1-CX3CL1/tumor-associated macrophage recruitment axis controls testicular germ cell tumor growth
Authors: Batool Aalia , Wang Yu-Qian , Hao Xiao-Xia , Chen Su-Ren , Liu Yi-Xun 
Published: September 2018

AbstractTumor growth is modulated by crosstalk between cancer cells and the tumor microenvironment. Recent advances have shown that miRNA dysfunction in tumor cells can modulate the tumor microenvironment to indirectly determine their progression. However, this process is poorly understood in testicular germ cell tumors (TGCTs). We reported here that miR-125b was repressed in TGCT samples by epigenetic modifications rather than genetic alternations. Furthermore, miR-125b overexpression significantly alleviated the tumor growth in two NCCIT human embryonic carcinoma xenograft models in vivo, whereas miR-125b did not stimulate autonomous tumor cell growth in vitro. Notably, forced expression of miR-125b in NCCIT embryonic carcinoma cells decreased the abundance of host tumor-associated macrophages (TAMs) within tumor microenvironment. Selective deletion of host macrophages by clodronate abolished the anti-tumoral ability of miR-125b in xenograft models. By RNA profiling, Western blot and luciferase reporter assay, we further observed that miR-125b directly regulated tumor cell-derived chemokine CSF1 and CX3CL1, which are known to control the recruitment of TAMs to tumor sites. Lastly, we found that one set of miRNAs, which are under the regulation of miR-125b, might convergently target CSF1/CX3CL1 in NCCIT cells using miRNA profiling. These findings uncover the anticancer effect of miR-125b via mediating tumor-stroma crosstalk in xenograft models of TGCTs and raise the possibility of targeting miR-125b as miRNA therapeutics.
IGF1R upregulation confers resistance to isoform-specific inhibitors of PI3K in PIK3CA-driven ovarian cancer
Authors: Zorea Jonatan , Prasad Manu , Cohen Limor , Li Nan , Schefzik Roman , Ghosh Susmita , Rotblat Barak , Brors Benedikt , Elkabets Moshe 
Published: September 2018

AbstractGenomic alterations (GA) in PIK3CA leads to the hyper-activation of the phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K) pathway in more than 20% of ovarian cancer (OC) patients. Therefore, PI3K therapies are under clinical evaluation for this subset of patients. Evidently, in clinical trials testing the efficacy of isoform-specific inhibitors of PI3K (PI3Ki), patients having a stable disease eventually relapse, as tumors become resistant to treatment. Hence, there is an urgent clinical need to develop new therapeutic combinations to improve the efficacy of PI3Ki in PIK3CA-driven OC patients. Here we identified the molecular mechanism that limits the efficacy of the beta-sparing PI3Ki, Taselisib (GDC0032), in PIK3CA-mutated OC cell lines (IGROV1 and OAW42) that acquired resistance to GDC0032. By comparing the molecular profile of GDC0032-sensitve and -resistant OC cell lines, we found that AKT/mTOR inhibition is required for GDC0032 efficacy. In resistant cells, the sustained activation of AKT/mTOR was regulated by the upregulation of the insulin growth factor 1 receptor (IGF1R). Knockdown of IGF1R re-sensitized cells to GDC0032 in vitro, and the combination of AEW541, an IGF1R inhibitor, with GDC0032 exhibited potent anti-tumor activity in vitro and in vivo. We further demonstrated that IGF1R regulates tumor cell proliferation in IGROV1 cells, whereas in OAW42, it determines autophagy as well. Overall, our findings suggest that the dual inhibition of PI3K and IGF1R may be considered as a new therapeutic strategy in PIK3CA-driven OC.