bluuebunny/crossref_metadata_2025 huggingface dataset:
To Do No Harm: Humanitarian Aid in Conflict Demands Political Engagement
Authors: Patel Ronak B. , Wild Hannah B.
Published: January 2018

Humanitarian aid in settings of conflict has always been fraught with challenges. In the absence of political engagement, however, manipulation by state authorities, however, have the potential to pervert aid intervention to inflict harm. South Sudan exemplifies how states may abuse the humanitarian response to retreat from public responsibility, divert funds to further violence and conflict and dictate the distribution of aid. Recent trends toward nationalist policies in the West that favor disengagement and limited military strikes have the very effect of allowing this abuse to transform humanitarian aid into a tool for harm. (Disaster Med Public Health Preparedness. 2018;12:567–568)
Extraction and evaluation of transportation network grammars for efficient planning applications
Authors: Vitins B. J. , Axhausen K. W.
Published: January 2018

Grammars, with their generic approach and broad application potential in many planning fields, are accepted as adaptable and efficient tools for design and planning applications, bridging design rules and technical planning requirements. This paper provides a formal introduction of grammars for effective consolidation and application, including a rule-based notation and required specification information. Two proposed grammar evaluation methods – based on technical planning knowledge and using recent computational development – foster understanding of a grammar’s effects, often missing in other definitions. Knowledge gained enables efficient grammar rule application, e.g. in burgeoning planning software. This research focuses particularly on urban network design and road intersection grammars to validate proposed grammar evaluation methods. Results are specified in the proposed grammar notation with corresponding application specifications. Results generally show that network topology and intersection type choice both depend on transport mode characteristics and flow. Specifically, medium-dense gridiron networks are car-efficient in terms of travel costs and reliability at urban densities, when combined with high road and intersection capacities. Pedestrian networks ideally have higher intersection and road densities with lower capacities than car networks. Highly meshed networks improve overall travel cost efficiencies for all transport modes at various flow levels.
External Appeal, Internal Dominance: How Party Leaders Contribute to Successful Party Building
Authors: Van Dyck Brandon
Published: January 2018

Many successful political parties depend for their initial popularity and cohesion, and even for their long-term brand strength, on a leader. Nevertheless, literature on successful party building downplays the role of leaders. Thus, the question, what type of leader is good for party building?, remains undertheorized. This article presents and provides initial evidence for a leadership-centered theory of successful party building. It argues that externally appealing, internally dominant leaders facilitate party building by lifting new parties to electoral prominence and helping to prevent debilitating schisms. The article provides evidence for this argument through a most similar cases comparison of three new left parties in Latin America: two that took root (Brazil’s Workers’ Party, Mexico’s Party of the Democratic Revolution), and one that collapsed (Peru’s United Left).
Setting the Regional Agenda: A Critique of Posthegemonic Regionalism
Authors: Petersen Mark , Schulz Carsten-Andreas
Published: January 2018

There is a growing scholarly consensus that Latin American regionalism has entered a new phase. For some observers, the increasing complexity of regional cooperation initiatives renders collective action ineffective. For others, the creation of new schemes signals a “posthegemonic” moment that has opened a space for collaboration on social issues. Both camps attribute this shift to the absence of the United States and the presence of left-leaning governments. By contrast, this study demonstrates that this agenda is not new, nor has the United States impeded similar initiatives in the past. In fact, the United States was instrumental in expanding regional cooperation on social issues in the early twentieth century. Instead, this article argues that agenda shifts are best explained by an evolving consensus about the role of the state. The “new agenda” is in line with historical attempts by governments to use regionalism to bolster their own domestic reforms.
Electoral Reform Under Limited Party Competition: The Adoption of Proportional Representation in Latin America
Authors: Negretto Gabriel L. , Visconti Giancarlo
Published: January 2018

The adoption of proportional representation in Western Europe has been portrayed as either a defensive or an offensive competition strategy used by established parties to deal with the rise of new parties under majoritarian electoral rules. Neither explanation accounts for PR reform in other regions of the world, where the change took place in the absence of increased party competition. Analyzing the history of electoral reform in Latin America, this article argues that in a context of limited party competition, the initial adoption of PR was part of a strategy of controlled political liberalization promoted by authoritarian rulers. Subdividing this general reasoning, the article shows that PR reform followed different paths depending on the nature of the authoritarian regime and the events that called into question the existing majoritarian electoral system. This argument is supported with a comparative historical analysis of cases within and across each route to reform.
The Racialized Effects of Social Programs in Brazil
Authors: De Micheli David
Published: January 2018

Studies of the electoral effects of cash transfer programs in Latin America have largely treated the poor as a unitary group. This study considers how the effects of social benefits vary across groups among the targeted poor by exploring the consequences of race for the electoral effects of Brazil’s Bolsa Família program. A matching analysis of LAPOP survey data shows that race shapes baseline propensities to participate in elections and to support the incumbent PT at the polls; these tendencies then shape the mechanisms through which cash transfers boost support for the incumbent. Benefits mobilize Afro-Brazilians to participate but have little effect on their vote choice. By contrast, benefits have little effect on whites’ participation but persuade them to support the PT over the opposition. This article deepens understanding of how social benefits affect the electoral behavior of recipients and highlights how race shapes political behavior among the poor.
Costs and Benefits of Overlapping Regional Organizations in Latin America: The Case of the OAS and UNASUR
Authors: Nolte Detlef
Published: January 2018

This article investigates whether the overlapping of intergovernmental regional organizations in Latin America with regard to membership and mandate is harmful or beneficial to regional cooperation (with a special focus on mediation in domestic and international conflicts). The article begins by systematizing the discussion about the possible risks and potential benefits of overlapping regional organizations, and then outlines hypotheses that can be tested in concrete episodes of overlap of action. The article then analyzes nine episodes in which an overlap of action has occurred between two Latin American organizations, the Organization of American States (OAS) and the Union of South American Nations (UNASUR). The results of the study are mixed. However, the effects of overlapping seem to be much less problematic than a large body of literature generally assumes.
The Role of Psychosocial Resources in the Adjustment of Migrant Adolescents
Authors: Darmanaki Farahani Leila , Bradley Graham L.
Published: January 2018

Adolescents who immigrate face particular adjustment challenges. This study investigated (a) levels of wellbeing and depression in migrant adolescents and their Australian native counterparts, (b) associations between adjustment and four psychosocial resources, and (c) moderating effects of country of birth on the relationships between these resources and adjustment indices. The sample ( N = 327) included students born in Australia, English-speaking countries other than Australia, and non-English-speaking countries. Students born outside of Australia in English-speaking countries reported highest mean levels of wellbeing and ethnic identity. Ethnic identity did not have the expected protective effects on migrant adolescent adjustment. In contrast, a sense of school membership affected Australian-born adolescents more positively than it did their overseas-born peers. The results raise questions regarding sources of support and connectedness that might particularly help migrant adolescents.
New medications for treatment-resistant depression: a brief review of recent developments
Authors: Thase Michael E.
Published: January 2018

There is a great unmet need for new medications with novel mechanisms of action that can effectively treat patients who do not benefit from standard antidepressant therapies. After a period in which it seemed as if the pharmaceutical pipeline for new antidepressants was going dry, the past decade has witnessed renewed interest, beginning with discovery of the antidepressant effects of ketamine. This article briefly highlights more recent research on ketamine and other investigational antidepressants.
Is language interference (when it occurs) agradedor anall-or-noneeffect? Evidence from bilingual reported speech production
Authors: HATZIDAKI ANNA , SANTESTEBAN MIKEL , DUYCK WOUTER
Published: January 2018

Do cross-lingual interactions occur even with structures of different word order in different languages of bilinguals? Or could the latter provide immunity to interference of the contrasting characteristics of the other language? To answer this question, we examined the reported speech production (utterances reporting what just happened; e.g.,Holly asked what Eric ate) of two groups of proficient, unbalanced bilinguals with varying similarity between their native (L1-Spanish/L1-Dutch) and second language (L2-English). The results showed that both groups of bilinguals produced word order errors when formulating indirectWhat-questions in L2, regardless of how similar the L1 was to the L2 in that respect. Our findings suggest that in the case of reported speech production in the examined bilingual groups, cross-linguistic syntactic differences by themselves suffice to induce language interference, and that the degree of similarity between the L1 and the L2 does not seem to modulate the magnitude of this effect.
The Effects of Betaine on the Nuclear Fractal Dimension, Chromatin Texture, and Proliferative Activity in Hepatocytes in Mouse Model of Nonalcoholic Fatty Liver Disease
Authors: Vesković Milena , Labudović-Borović Milica , Zaletel Ivan , Rakočević Jelena , Mladenović Dušan , Jorgačević Bojan , Vučević Danijela , Radosavljević Tatjana
Published: January 2018

The effects of betaine on hepatocytes chromatin architecture changes were examined by using fractal and gray-level co-occurrence matrix (GLCM) analysis in methionine/choline-deficient (MCD) diet-induced, nonalcoholic fatty liver disease (NAFLD). Male C57BL/6 mice were divided into groups: (1) Control: standard diet; (2) BET: standard diet and betaine supplementation through drinking water (solution 1.5%); (3) MCD group: MCD diet for 6 weeks; (4) MCD+BET: fed with MCD diet + betaine for 6 weeks. Liver tissue was collected for histopathology, immunohistochemistry, and determination of fractal dimension and GLCM parameters. MCD diet induced diffuse micro- and macrovesicular steatosis accompanied with increased Ki67-positive hepatocyte nuclei. Steatosis and Ki67 immunopositivity were less prominent in the MCD+BET group compared with the MCD group. Angular second moment (ASM) and inverse difference moment (IDM) (textural homogeneity markers) were significantly increased in the MCD+BET group versus the MCD group (p<0.001), even though no difference between the MCD and the control group was evident. Heterogeneity parameters, contrast, and correlation were significantly increased in the MCD group versus the control (p<0.001). On the other hand, betaine treatment significantly reduced correlation, contrast, and entropy compared with the MCD group (p<0.001). Betaine attenuated MCD diet-induced NAFLD by reducing fat accumulation and inhibiting hepatocyte proliferation. Betaine supplementation increased nuclear homogeneity and chromatin complexity with reduction of entropy, contrast, and correlation.
Evaluation of Chemical Termination Options for Cover Crops
Authors: Palhano Matheus G. , Norsworthy Jason K. , Barber Tom
Published: January 2018

Cover crop acreage has substantially increased over the last few years due to the intent of growers to capitalize on federal conservation payments and incorporate sustainable practices into agricultural systems. Despite all the known benefits, widespread adoption of cover crops still remains limited due to potential cost and management requirements. Cover crop termination is crucial, because a poorly controlled cover crop can become a weed and lessen the yield potential of the current cash crop. A field study was conducted in fall 2015 and 2016 at the Arkansas Agricultural Research and Extension Center in Fayetteville to evaluate preplant herbicide options for terminating cover crops. Glyphosate-containing treatments controlled 97% to 100% of cereal rye and wheat, but glyphosate alone controlled less than 57% of legume cover crops. The most effective way to control hairy vetch, Austrian winterpea, and crimson clover with glyphosate resulted from mixtures of glyphosate with glufosinate, 2,4-D, and dicamba. Higher rates of auxin herbicides improved control in these mixtures. Glufosinate alone or in mixture controlled legume cover crops 81% or more. Paraquat plus metribuzin was effective in terminating both cereal and legume cover crops, with control of cereal cover crops ranging from 87% to 97% and control of legumes ranging from 90% to 96%. None of these herbicides or mixtures adequately controlled rapeseed.
Das Kind mit einer Hörbeeinträchtigung im Spital. Wie Eltern die Kommunikation zwischen Pflegenden und ihrem Kind erleben
Authors: Brooks Seraina , Eckerli-Wäspi Irene , Händler Schuster Daniela
Published: January 2018

Zusammenfassung.Hintergrund: Kinder mit einer Hörbeeinträchtigung sind in der alltäglichen Kommunikation eingeschränkt und auf elterliche Unterstützung angewiesen. Während eines Spitalaufenthalts ist die Gefahr unzureichender Informationsvermittlung und daraus resultierender Traumatisierungen des Kindes groß. Ziel dieser Studie ist es, die kommunikativen Bedürfnisse der Kinder aus Sicht der Eltern zu erforschen, um negative Konsequenzen eines Spitalaufenthalts und unangemessener Kommunikation durch Pflegende für das Kind zu vermeiden. Ziel: Mit dieser Studie wurde exploriert, wie Eltern eines Kindes mit einer Hörbeeinträchtigung die Kommunikation zwischen Pflegenden und ihrem Kind im Spital erleben. Methode: In Zusammenarbeit mit einer Beratungsstelle für hörbeeinträchtigte Kinder wurden die meisten Eltern rekrutiert. Es wurden narrative semistrukturierte Leitfaden-Interviews geführt. Diese wurden transkribiert und nach der Methode der interpretativen Phänomenologie analysiert. Ergebnisse: Die Eltern wünschen sich liebevolle verbale oder nonverbale Zuwendung für ihr Kind. Sie erlebten häufig, wie Pflegende wenig Zeit hatten, wie Kontinuität fehlte und wie die kommunikativen Bedürfnisse des Kindes nicht erkannt wurden. Da die Eltern den Pflegenden die Kommunikation mit dem Kind nicht zutrauten und es schützen wollten, nahmen sie eine vermittelnde Rolle ein. Schlussfolgerungen: Die Pflege eines Kindes mit einer Hörbeeinträchtigung erfordert neben der Sensibilisierung der Pflegenden Zeitressourcen, Kontinuität, Fürsorge und Fachwissen.
Targeting IL-2: an unexpected effect in treating immunological diseases
Authors: Ye Congxiu , Brand David , Zheng Song G.
Published: January 2018

Regulatory T cells (Treg) play a crucial role in maintaining immune homeostasis since Treg dysfunction in both animals and humans is associated with multi-organ autoimmune and inflammatory disease. While IL-2 is generally considered to promote T-cell proliferation and enhance effector T-cell function, recent studies have demonstrated that treatments that utilize low-dose IL-2 unexpectedly induce immune tolerance and promote Treg development resulting in the suppression of unwanted immune responses and eventually leading to treatment of some autoimmune disorders. In the present review, we discuss the biology of IL-2 and its signaling to help define the key role played by IL-2 in the development and function of Treg cells. We also summarize proof-of-concept clinical trials which have shown that low-dose IL-2 can control autoimmune diseases safely and effectively by specifically expanding and activating Treg. However, future studies will be needed to validate a better and safer dosing strategy for low-dose IL-2 treatments utilizing well-controlled clinical trials. More studies will also be needed to validate the appropriate dose of IL-2/anti-cytokine or IL-2/anti-IL-2 complex in the experimental animal models before moving to the clinic.
FBXL10 contributes to the development of diffuse large B-cell lymphoma by epigenetically enhancing ERK1/2 signaling pathway
Authors: Zhao Xiujuan , Wang Xing , Li Qian , Chen Wanbiao , Zhang Na , Kong Yu , Lv Junqiang , Cao Lei , Lin Dan , Wang Xi , Xu Guogang , Wu Xudong
Published: January 2018

Epigenetic modifiers have emerged as critical factors governing the biology of different cancers. Herein we show that FBXL10 (also called KDM2B or JHDM1B), an important member of Polycomb repressive complexes, is overexpressed in human diffuse large B-cell lymphoma (DLBCL) tissues and the derived cell lines. Knocking down FBXL10 by specific short hairpin RNAs in DLBCL cells inhibits cell proliferation and induces apoptosis in vitro. Moreover, FBXL10 depletion in DLBCL cells abrogates tumor growth in mouse xenograft models. Through the analysis of RNA sequencing, we find that one of the key derepressed genes by depletion of FBXL10 is DUSP6, encoding a phosphatase for ERK1/2. Mechanistically FBXL10 maintains the silencing of DUSP6 expression via recruitment of Polycomb group proteins and deposition of repressive histone modifications at the DUSP6 promoter. Consistently, FBXL10 is required for ERK1/2 phosphorylation in DLBCL cells. Furthermore, we show that ERK1/2 activation and the proliferation rate of FBXL10-depleted cells can be rescued by downregulation of DUSP6 expression. These findings indicate that FBXL10 may be a promising therapeutic target in DLBCL and establish a link of epigenetic regulators to kinase signaling pathways.
Nucleolin and ErbB2 inhibition reduces tumorigenicity of ErbB2-positive breast cancer
Authors: Wolfson Eya , Solomon Shira , Schmukler Eran , Goldshmit Yona , Pinkas-Kramarski Ronit
Published: January 2018

ErbB2, a member of the ErbB family of receptor tyrosine kinases, is an essential player in the cell’s growth and proliferation signaling pathways. Amplification or overexpression of ErbB2 is observed in ∼30% of breast cancer patients, and often drives cellular transformation and cancer development. Recently, we have shown that ErbB2 interacts with the nuclear-cytoplasmic shuttling protein nucleolin, an interaction which enhances cell transformation in vitro, and increases mortality risk and disease progression rate in human breast cancer patients. Given these results, and since acquired resistance to anti-ErbB2-targeted therapy is a major obstacle in treatment of breast cancer, we have examined the therapeutic potential of targeting the ErbB2–nucleolin complex. The effect of the nucleolin-specific inhibitor GroA (AS1411) on ErbB2-positive breast cancer was tested in vivo, in a mouse xenograft model for breast cancer; as well as in vitro, alone and in combination with the ErbB2 kinase-inhibitor tyrphostin AG-825. Here, we show that in vivo treatment of ErbB2-positive breast tumor xenografts with GroA reduces tumor size and leads to decreased ErbB2-mediated signaling. Moreover, we found that co-treatment of breast cancer cell lines with GroA and the ErbB2 kinase-inhibitor tyrphostin AG-825 enhances the anti-cancer effects exerted by GroA alone in terms of cell viability, mortality, migration, and invasiveness. We, therefore, suggest a novel therapeutic approach, consisting of combined inhibition of ErbB2 and nucleolin, which has the potential to improve breast cancer treatment efficacy.
Melatonin inhibits apoptotic cell death induced by Vibrio vulnificus VvhA via melatonin receptor 2 coupling with NCF-1
Authors: Lee Sei-Jung , Lee Hyun Jik , Jung Young Hyun , Kim Jun Sung , Choi Sang Ho , Han Ho Jae
Published: January 2018

Melatonin, an endogenous hormone molecule, has a variety of biological functions, but a functional role of melatonin in the infection of Gram-negative bacterium Vibrio vulnificus has yet to be described. In this study, we investigated the molecular mechanism of melatonin in the apoptosis of human intestinal epithelial (HCT116) cells induced by the hemolysin (VvhA) produced by V. vulnificus. Melatonin (1 μM) significantly inhibited apoptosis induced by the recombinant protein (r) VvhA, which had been inhibited by the knockdown of MT2. The rVvhA recruited caveolin-1, NCF-1, and Rac1 into lipid rafts to facilitate the production of ROS responsible for the phosphorylation of PKC and JNK. Interestingly, melatonin recruited NCF-1 into non-lipid rafts to prevent ROS production via MT2 coupling with Gαq. Melatonin inhibited the JNK-mediated phosphorylation of c-Jun responsible for Bax expression, the release of mitochondrial cytochrome c, and caspase-3/-9 activation during its promotion of rVvhA-induced apoptotic cell death. In addition, melatonin inhibited JNK-mediated phosphorylation of Bcl-2 responsible for the release of Beclin-1 and Atg5 expression during its promotion of rVvhA-induced autophagic cell death. These results demonstrate that melatonin signaling via MT2 triggers recruitment of NCF-1 into non-lipid rafts to block ROS production and JNK-mediated apoptotic and autophagic cell deaths induced by rVvhA in intestinal epithelial cells.
ZEB1 confers chemotherapeutic resistance to breast cancer by activating ATM
Authors: Zhang Xiang , Zhang Zhen , Zhang Qing , Zhang Quansheng , Sun Peiqing , Xiang Rong , Ren Guosheng , Yang Shuang
Published: January 2018

Although zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key factor in the regulation of breast cancer differentiation and metastasis, its potential role in modulating tumor chemoresistance has not been fully understood. Here, through the study of specimens from a large cohort of human breast cancer subjects, we showed that patients with tumors that expressed high levels of ZEB1 responded poorly to chemotherapy. Moreover, ZEB1 expression was positively correlated with expression of B-cell lymphoma-extra large (Bcl-xL) and cyclin D1, which are key components of tumor chemoresistant mechanisms. At the molecular level, ectopic expression of ZEB1 impaired the responsiveness of breast cancer cells to genotoxic drug treatment, such as epirubicin (EPI). During this process, ZEB1 transcriptionally activated the expression of ataxia-telangiectasia mutated (ATM) kinase by forming a ZEB1/p300/PCAF complex on its promoter, leading to increased homologous recombination (HR)-mediated DNA damage repair and the clearance of DNA breaks. Using a nude mouse xenograft model, we further confirmed that ectopic expression of ZEB1 decreased breast cancer responsiveness to EPI treatment in vivo. Collectively, our findings suggest that ZEB1 is a crucial determinant of chemotherapeutic resistance in breast cancer.
U-box ubiquitin ligase PPIL2 suppresses breast cancer invasion and metastasis by altering cell morphology and promoting SNAI1 ubiquitination and degradation
Authors: Jia Zhaojun , Wang Miao , Li Shujing , Li Xiahui , Bai Xiao-Yan , Xu Zhaowei , Yang Yangyang , Li Bowen , Li Yanan , Wu Huijian
Published: January 2018

Metastasis is the leading cause of breast cancer fatalities. To develop new therapeutic strategies, the mechanisms underlying breast cancer invasion and metastasis need to be further investigated. Peptidylprolyl isomerase (cyclophilin)-like 2 (PPIL2) is a U-box-type E3 ubiquitin ligase belonging to the cyclophilin family. Proteins within this family are the major cytosolic binding proteins of the immunosuppressant drug cyclosporine A (CsA). Although PPIL2 has been reported to potentially be involved in cell migration, its role in breast cancer is still unclear. Herein, we demonstrate that PPIL2 suppressed metastasis in a breast cancer model by altering cell morphology and suppressing the epithelial–mesenchymal transition (EMT) process. Moreover, elevated PPIL2 inhibited EMT and breast cancer invasion by interacting with the classical EMT transcription factor, SNAI1, to enhance its ubiquitin-dependent degradation. Furthermore, PPIL2 protein level and stability was upregulated after CsA treatment, indicating that PPIL2 might be involved in CsA-mediated repression of EMT in breast cancer. Analysis of tissue samples taken from breast cancer patients showed a significant correlation between the expression of PPIL2 and the degree of cancer invasion and metastasis. In summary, these results would shed light on a potential clinical use of CsA in breast cancer patients.
STIL balancing primary microcephaly and cancer
Authors: Patwardhan Dhruti , Mani Shyamala , Passemard Sandrine , Gressens Pierre , El Ghouzzi Vincent
Published: January 2018

Cell division and differentiation are two fundamental physiological processes that need to be tightly balanced to achieve harmonious development of an organ or a tissue without jeopardizing its homeostasis. The role played by the centriolar protein STIL is highly illustrative of this balance at different stages of life as deregulation of the human STIL gene expression has been associated with either insufficient brain development (primary microcephaly) or cancer, two conditions resulting from perturbations in cell cycle and chromosomal segregation. This review describes the recent advances on STIL functions in the control of centriole duplication and mitotic spindle integrity, and discusses how pathological perturbations of its finely tuned expression result in chromosomal instability in both embryonic and postnatal situations, highlighting the concept that common key factors are involved in developmental steps and tissue homeostasis.
SWELL1 is a glucose sensor regulating β-cell excitability and systemic glycaemia
Authors: Kang Chen , Xie Litao , Gunasekar Susheel K. , Mishra Anil , Zhang Yanhui , Pai Saachi , Gao Yiwen , Kumar Ashutosh , Norris Andrew W. , Stephens Samuel B. , Sah Rajan
Published: January 2018

Insulin secretion is initiated by activation of voltage-gated Ca2+ channels (VGCC) to trigger Ca2+-mediated insulin vesicle fusion with the β-cell plasma membrane. The firing of VGCC requires β-cell membrane depolarization, which is regulated by a balance of depolarizing and hyperpolarizing ionic currents. Here, we show that SWELL1 mediates a swell-activated, depolarizing chloride current (ICl,SWELL) in both murine and human β-cells. Hypotonic and glucose-stimulated β-cell swelling activates SWELL1-mediated ICl,SWELL and this contributes to membrane depolarization and activation of VGCC-dependent intracellular calcium signaling. SWELL1 depletion in MIN6 cells and islets significantly impairs glucose-stimulated insulin secretion. Tamoxifen-inducible β-cell-targeted Swell1 KO mice have normal fasting serum glucose and insulin levels but impaired glucose-stimulated insulin secretion and glucose tolerance; and this is further exacerbated in mild obesity. Our results reveal that β-cell SWELL1 modulates insulin secretion and systemic glycaemia by linking glucose-mediated β-cell swelling to membrane depolarization and activation of VGCC-triggered calcium signaling.
Lsd1 regulates skeletal muscle regeneration and directs the fate of satellite cells
Authors: Tosic Milica , Allen Anita , Willmann Dominica , Lepper Christoph , Kim Johnny , Duteil Delphine , Schüle Roland
Published: January 2018

Satellite cells are muscle stem cells required for muscle regeneration upon damage. Of note, satellite cells are bipotent and have the capacity to differentiate not only into skeletal myocytes, but also into brown adipocytes. Epigenetic mechanisms regulating fate decision and differentiation of satellite cells during muscle regeneration are not yet fully understood. Here, we show that elevated levels of lysine-specific demethylase 1 (Kdm1a, also known as Lsd1) have a beneficial effect on muscle regeneration and recovery after injury, since Lsd1 directly regulates key myogenic transcription factor genes. Importantly, selective Lsd1 ablation or inhibition in Pax7-positive satellite cells, not only delays muscle regeneration, but changes cell fate towards brown adipocytes. Lsd1 prevents brown adipocyte differentiation of satellite cells by repressing expression of the novel pro-adipogenic transcription factor Glis1. Together, downregulation of Glis1 and upregulation of the muscle-specific transcription program ensure physiological muscle regeneration.
Closed-loop stimulation of temporal cortex rescues functional networks and improves memory
Authors: Ezzyat Youssef , Wanda Paul A. , Levy Deborah F. , Kadel Allison , Aka Ada , Pedisich Isaac , Sperling Michael R. , Sharan Ashwini D. , Lega Bradley C. , Burks Alexis , Gross Robert E. , Inman Cory S. , Jobst Barbara C. , Gorenstein Mark A. , Davis Kathryn A. , Worrell Gregory A. , Kucewicz Michal T. , Stein Joel M. , Gorniak Richard , Das Sandhitsu R. , Rizzuto Daniel S. , Kahana Michael J.
Published: January 2018

Memory failures are frustrating and often the result of ineffective encoding. One approach to improving memory outcomes is through direct modulation of brain activity with electrical stimulation. Previous efforts, however, have reported inconsistent effects when using open-loop stimulation and often target the hippocampus and medial temporal lobes. Here we use a closed-loop system to monitor and decode neural activity from direct brain recordings in humans. We apply targeted stimulation to lateral temporal cortex and report that this stimulation rescues periods of poor memory encoding. This system also improves later recall, revealing that the lateral temporal cortex is a reliable target for memory enhancement. Taken together, our results suggest that such systems may provide a therapeutic approach for treating memory dysfunction.
The creation of electric wind due to the electrohydrodynamic force
Authors: Park Sanghoo , Cvelbar Uros , Choe Wonho , Moon Se Youn
Published: January 2018

Understanding the interactions between ionized matter and neutral particles is a prerequisite for discovering their impact on natural phenomena. One such phenomenon is the electric wind, which supposedly occurs due to the charged particle–neutral coupling in systems of weakly ionized gases, but this mechanism remains unclear. Here, we report direct evidence that electric wind is caused by an electrohydrodynamic force generated by the charged particle drag as a result of the momentum transfer from electrons/ions to neutrals. The model experiment is based on a pulsed plasma jet as a source of weakly ionized gases generated in the helium gas at atmospheric pressure using Schlieren photography. Studying the helium gas flow trajectories at different discharge parameters allows one to distinguish between the effects of streamer propagation or space charge drift causing the electric wind as well as to determine the role of electrons and (positive) ions in wind generation.
The ecological origins of snakes as revealed by skull evolution
Authors: Da Silva Filipe O. , Fabre Anne-Claire , Savriama Yoland , Ollonen Joni , Mahlow Kristin , Herrel Anthony , Müller Johannes , Di-Poï Nicolas
Published: January 2018

The ecological origin of snakes remains amongst the most controversial topics in evolution, with three competing hypotheses: fossorial; marine; or terrestrial. Here we use a geometric morphometric approach integrating ecological, phylogenetic, paleontological, and developmental data for building models of skull shape and size evolution and developmental rate changes in squamates. Our large-scale data reveal that whereas the most recent common ancestor of crown snakes had a small skull with a shape undeniably adapted for fossoriality, all snakes plus their sister group derive from a surface-terrestrial form with non-fossorial behavior, thus redirecting the debate toward an underexplored evolutionary scenario. Our comprehensive heterochrony analyses further indicate that snakes later evolved novel craniofacial specializations through global acceleration of skull development. These results highlight the importance of the interplay between natural selection and developmental processes in snake origin and diversification, leading first to invasion of a new habitat and then to subsequent ecological radiations.
AMPK activation counteracts cardiac hypertrophy by reducing O-GlcNAcylation
Authors: Gélinas Roselle , Mailleux Florence , Dontaine Justine , Bultot Laurent , Demeulder Bénédicte , Ginion Audrey , Daskalopoulos Evangelos P. , Esfahani Hrag , Dubois-Deruy Emilie , Lauzier Benjamin , Gauthier Chantal , Olson Aaron K. , Bouchard Bertrand , Des Rosiers Christine , Viollet Benoit , Sakamoto Kei , Balligand Jean-Luc , Vanoverschelde Jean-Louis , Beauloye Christophe , Horman Sandrine , Bertrand Luc
Published: January 2018

AMP-activated protein kinase (AMPK) has been shown to inhibit cardiac hypertrophy. Here, we show that submaximal AMPK activation blocks cardiomyocyte hypertrophy without affecting downstream targets previously suggested to be involved, such as p70 ribosomal S6 protein kinase, calcineurin/nuclear factor of activated T cells (NFAT) and extracellular signal-regulated kinases. Instead, cardiomyocyte hypertrophy is accompanied by increased protein O-GlcNAcylation, which is reversed by AMPK activation. Decreasing O-GlcNAcylation by inhibitors of the glutamine:fructose-6-phosphate aminotransferase (GFAT), blocks cardiomyocyte hypertrophy, mimicking AMPK activation. Conversely, O-GlcNAcylation-inducing agents counteract the anti-hypertrophic effect of AMPK. In vivo, AMPK activation prevents myocardial hypertrophy and the concomitant rise of O-GlcNAcylation in wild-type but not in AMPKα2-deficient mice. Treatment of wild-type mice with O-GlcNAcylation-inducing agents reverses AMPK action. Finally, we demonstrate that AMPK inhibits O-GlcNAcylation by mainly controlling GFAT phosphorylation, thereby reducing O-GlcNAcylation of proteins such as troponin T. We conclude that AMPK activation prevents cardiac hypertrophy predominantly by inhibiting O-GlcNAcylation.
Author Correction: In situ assembly of Ag nanoparticles (AgNPs) on porous silkworm cocoon-based wound film: enhanced antimicrobial and wound healing activity
Authors: Yu Kun , Lu Fei , Li Qing , Chen Honglei , Lu Bitao , Liu Jiawei , Li Zhiquan , Dai Fangying , Wu Dayang , Lan Guangqian
Published: January 2018

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
Pervasive Rise of Small-scale Deforestation in Amazonia
Authors: Kalamandeen Michelle , Gloor Emanuel , Mitchard Edward , Quincey Duncan , Ziv Guy , Spracklen Dominick , Spracklen Benedict , Adami Marcos , Aragão Luiz E. O. C. , Galbraith David
Published: January 2018

Understanding forest loss patterns in Amazonia, the Earth’s largest rainforest region, is critical for effective forest conservation and management. Following the most detailed analysis to date, spanning the entire Amazon and extending over a 14-year period (2001–2014), we reveal significant shifts in deforestation dynamics of Amazonian forests. Firstly, hotspots of Amazonian forest loss are moving away from the southern Brazilian Amazon to Peru and Bolivia. Secondly, while the number of new large forest clearings (>50 ha) has declined significantly over time (46%), the number of new small clearings (<1 ha) increased by 34% between 2001–2007 and 2008–2014. Thirdly, we find that small-scale low-density forest loss expanded markedly in geographical extent during 2008–2014. This shift presents an important and alarming new challenge for forest conservation, despite reductions in overall deforestation rates.
PD-L1 reverses depigmentation in Pmel-1 vitiligo mice by increasing the abundance of Tregs in the skin
Authors: Miao Xiao , Xu Rong , Fan Bin , Chen Jie , Li Xin , Mao Weiwei , Hua Shengyuan , Li Bin
Published: January 2018

Programmed cell death 1 ligand 1 (PD-L1) is a ligand of programmed cell death 1 (PD-1) that functions as an immune checkpoint by down-regulating immune responses. To determine whether PD-L1 is a therapy target in vitiligo treatment, Pmel-1 vitiligo mice were treated with a PD-L1 fusion protein. Treatment with this fusion protein significantly reversed/suppressed depigmentation development in adult Pmel-1 mice. Mechanistically, enrichment of regulatory T cells (Treg) in the skin was detected after PD-L1 fusion protein treatment in Pmel-1 mice. Furthermore, Tregs abundance was also increased in both the spleen and circulation of Pmel-1 mice treated with PD-L1. These data indicate that PD-L1 protein therapy inhibits the immune response and reverses depigmentation development in Pmel-1 vitiligo mice.
Human Rhinovirus 3C protease cleaves RIPK1, concurrent with caspase 8 activation
Authors: Croft Sarah N. , Walker Erin J. , Ghildyal Reena
Published: January 2018

Human Rhinovirus (HRV) is a pathogen of significant medical importance, being a major cause of upper respiratory tract infections (common colds) as well as causing the majority of virus-induced asthma exacerbations. We investigated whether HRV could modulate apoptosis, an innate antiviral response. Apoptotic signals are generated either extrinsically or intrinsically and are propagated via caspase cascades that lead to cell death, reducing viral replication, which relies on cellular machinery. Using HRV16 infected cells, in combination with chemical inducers and inhibitors of extrinsic apoptosis we show that HRV16 3C protease cleaves a key intermediate in extrinsic apoptosis. Receptor-interacting protein kinase-1 (RIPK1), an extrinsic apoptosis adaptor protein, was cleaved by caspase 8, as expected, during chemical induction of apoptosis. RIPK1 was cleaved in HRV infection albeit at a different site. Caspase 8 activation, which is associated with extrinsic apoptosis, was concurrent with HRV 3C protease mediated cleavage of RIPK1, and potentially increased the accessibility of the HRV 3C cleavage site within RIPK1 in-vitro. The caspase 8 mediated RIPK1 cleavage product has a pro-apoptotic function, and further cleavage of this pro-apoptotic cleavage product by HRV 3C may provide a mechanism by which HRV limits apoptosis.
Simultaneous bilateral total knee arthroplasty in patients with end-stage hemophilic arthropathy: a mean follow-up of 6 years
Authors: Jiang Chao , Zhao Yan , Feng Bin , Zhai Jiliang , Bian Yanyan , Qiu Guixing , Weng Xisheng
Published: January 2018

To investigate the safety, cost-effectiveness, and clinical outcomes of simultaneous bilateral total knee arthroplasty (TKA) in hemophilic arthropathy (HA), the requirements for transfusions, complications, costs, hospital stays, Hospital for Special Surgery (HSS) knee scores, knee range of motion (ROM) and revision rates were compared between simultaneous bilateral and unilateral TKA in HA patients. A total of 36 patients and 54 knees were included. Compared to the unilateral group, the bilateral group did not require more transfusions (2.39 ± 3.13 vs 0.83 ± 1.38 units of RBCs, p > 0.05) or consumption of coagulation factors (50091.67 ± 25168.5 vs 46477.78 ± 11348.32 IU, p > 0.05), complications rate (13/36 vs 6/18, p > 0.05), hospital stay (32.39 ± 19.77 vs 29.11 ± 12.67 days, p > 0.05), or costs excluding prostheses (14945.41 ± 6634.35 vs 14742.12 ± 5746.78 US dollars, p > 0.05). Additionally, the two groups exhibited similar medium-term knee HSS scores (83.67 ± 7.11 vs 81.00 ± 10.35, p > 0.05) and ROM (89.39° ± 13.66° vs 88.91° ± 12.90°, p > 0.05). Our data indicate that bilateral TKA is a safe and cost-effective treatment for HA with similar medium-term results compared to unilateral TKA.
The MDM2-p53 pathway is involved in preconditioning-induced neuronal tolerance to ischemia
Authors: Vecino Rebeca , Burguete Maria C. , Jover-Mengual Teresa , Agulla Jesus , Bobo-Jiménez Verónica , Salom Juan B. , Almeida Angeles , Delgado-Esteban Maria
Published: January 2018

Brain preconditioning (PC) refers to a state of transient tolerance against a lethal insult that can be evoked by a prior mild event. It is thought that PC may induce different pathways responsible for neuroprotection, which may involve the attenuation of cell damage pathways, including the apoptotic cell death. In this context, p53 is a stress sensor that accumulates during brain ischemia leading to neuronal death. The murine double minute 2 gene (MDM2), a p53-specific E3 ubiquitin ligase, is the main cellular antagonist of p53, mediating its degradation by the proteasome. Here, we study the role of MDM2-p53 pathway on PC-induced neuroprotection both in cultured neurons (in vitro) and rat brain (in vivo). Our results show that PC increased neuronal MDM2 protein levels, which prevented ischemia-induced p53 stabilization and neuronal death. Indeed, PC attenuated ischemia-induced activation of the p53/PUMA/caspase-3 signaling pathway. Pharmacological inhibition of MDM2-p53 interaction in neurons abrogated PC-induced neuroprotection against ischemia. Finally, the relevance of the MDM2-p53 pathway was confirmed in rat brain using a PC model in vivo. These findings demonstrate the key role of the MDM2-p53 pathway in PC-induced neuroprotection against a subsequent ischemic insult and poses MDM2 as an essential target in ischemic tolerance.
Alternating Droplet Formation by using Tapered Channel Geometry
Authors: Saqib Muhammad , Şahinoğlu O. Berkay , Erdem E. Yegân
Published: January 2018

The ability to produce a controlled sequence of alternating droplets from two separate sources inside a microfluidic system brings several advantages in microfluidic analysis. The effectiveness of this technique for use in an application depends on the ability of the device to replicate the pattern continuously and accurately. In this work we studied the effect of the dispersed phase channel geometry on generating a repeating pattern of alternating droplets in a cross junction microfluidic device. By measuring the radius of curvature of a droplet at the time of break up, and calculating the Laplace pressure using these values, we analyzed how the angle of taper of the dispersed phase inlet channel has an influence on the pattern repetition and uniformity of formed droplet size and spacing in between. The performance of devices with different angle of taper values were studied experimentally. This comparative study indicated that the ability of a cross junction device to generate alternating droplets with uniform size and spacing is highly dependent on the angle of taper of the inlet channels; and it improves with larger taper angles.
Contrasting temperature trends across the ice-free part of Greenland
Authors: Westergaard-Nielsen Andreas , Karami Mojtaba , Hansen Birger Ulf , Westermann Sebastian , Elberling Bo
Published: January 2018

Temperature changes in the Arctic have notable impacts on ecosystem structure and functioning, on soil carbon dynamics, and on the stability of permafrost, thus affecting ecosystem functions and putting man-built infrastructure at risk. Future warming in the Arctic could accelerate important feedbacks in permafrost degradation processes. Therefore it is important to map vulnerable areas most likely to be impacted by temperature changes and at higher risk of degradation, particularly near communities, to assist adaptation to climate change. Currently, these areas are poorly assessed, especially in Greenland. Here we quantify trends in satellite-derived land surface temperatures and modelled air temperatures, validated against observations, across the entire ice-free Greenland. Focus is on the past 30 years, to characterize significant changes and potentially vulnerable regions at a 1 km resolution. We show that recent temperature trends in Greenland vary significantly between seasons and regions and that data with resolutions down to single km2 are critical to map temperature changes for guidance of further local studies and decision-making. Only a fraction of the ice-free Greenland seems vulnerable due to warming when analyzing year 2001–2015, but the most pronounced changes are found in the most populated parts of Greenland. As Greenland represents important gradients of north/south coast/inland/distance to large ice sheets, the conclusions are also relevant in an upscaling to greater Arctic areas.
Synthesis and growth-inhibitory activities of imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamides related to the anti-tumour drug temozolomide, with appended silicon, benzyl and heteromethyl groups at the 3-position
Authors: Cousin David , Hummersone Marc G. , Bradshaw Tracey D. , Zhang Jihong , Moody Christopher J. , Foreiter Magdalena B. , Summers Helen S. , Lewis William , Wheelhouse Richard T. , Stevens Malcolm F. G.
Published: January 2018

The synthesis and biological evaluation of imidazotetrazines substituted at N-3 is described.
Viable stretchable plasmonics based on unidirectional nanoprisms
Authors: Lee Ji-Eun , Park Choojin , Chung Kyungwha , Lim Ju Won , Marques Mota Filipe , Jeong Unyong , Kim Dong Ha
Published: January 2018

Unique plasmon-coupling-based SERS properties were investigated based on unidirectional nanoprisms on stretchable substrates, which were corroborated by near-field coupling of surface plasmons. A specific configuration with tailored composition and stimuli-induced geometrical control exhibited highest sensing activity.
Homogenous photopolymerization of acrylic monomers initiated with ZnO-methacrylate in non-aqueous medium and production of luminescent nanocomposites
Authors: Ulku Irem , Morlet-Savary Fabrice , Lalevée Jacques , Yagci Acar Havva
Published: January 2018

Luminescent ZnO quantum dots coated with methacrylic acid initiate photopolymerization of methylmethacrylate in the absence of hole-scavengers producing luminescent nanocomposites.
Dual-responsive biocompatible microgels as high loaded cargo: understanding of encapsulation/release driving forces by NMR NOESY
Authors: Aguirre Garbiñe , Khoukh Abdeld , Chougrani Kamel , Alard Valérie , Billon Laurent
Published: January 2018

The suitability of biocompatible microgels as a new cosmetic carrier has been demonstrated through their ability of encapsulation/release of cosmetic active molecules.
Self-exfoliation of 2D covalent organic frameworks: morphology transformation induced by solvent polarity
Authors: Zhang Na , Wang Taisheng , Wu Xing , Jiang Chen , Chen Fang , Bai Wei , Bai Ruke
Published: January 2018

Self-exfoliation of boron-containing covalent organic frameworks (COFs) and their morphology transformation induced by solvent polarity.
Chitosan composite scaffolds for articular cartilage defect repair: a review
Authors: Li Huijun , Hu Cheng , Yu Huijun , Chen Chuanzhong
Published: January 2018

Properties of chitosan/polymer and chitosan/bioceramic composite scaffolds for articular cartilage defect repair are reviewed.
A rapid and simple UPLC-MS/MS method using collagen marker peptides for identification of porcine gelatin
Authors: Guo Shangwei , Xu Xiaobing , Zhou Xiangshan , Huang Yaqin
Published: January 2018

Gelatin, which is mainly derived from bovine and porcine sources, has been used in many foods and pharmaceutical products.