bluuebunny/crossref_metadata_2025_split huggingface dataset:
What does community participation in nature protection mean? The case of tropical national parks in Africa
Authors: VIMAL RUPPERT , KHALIL-LORTIE MAUDE , GATISO TSEGAYE 
Published: January 2018

SUMMARYIn spite of significant investment, community-based conservation often suffers from a lack of appropriate design. In this study, drawing on 86 interviews around six national parks in tropical Africa, we analyse the perceptions of different stakeholders (e.g. governmental officials, non-governmental organization staff and researchers) regarding community participation. Our results mainly reveal the absence of a clear and shared definition of community participation. While 67% of the participants defined community participation as a community's support of nature protection (low empowerment) and/or as its participation in conservation implementation (medium empowerment), 28% mentioned that the community should also participate in decision-making (high empowerment). Our study shows that participants with no university degree, belonging to governmental organizations and/or employed as workers tend to propose a lower level of empowerment, while those educated to a postgraduate level, belonging to research institutes and/or employed as researchers propose higher degrees of empowerment. Our study mainly suggests that the different degrees of empowerment proposed by the stakeholders depend on their relation to the space of conservation and their daily connection to practical management as drivers of the inclusion or exclusion of local communities in conservation decision-making. To properly design and implement community-based conservation, conservation actors above all must share a common definition of the concept.
Vaccine effectiveness and use of collar impregnated with insecticide for reducing incidence of Leishmania infection in dogs in an endemic region for visceral leishmaniasis, in Brazil
Authors: Lopes E. G. , Sevá A. P. , Ferreira F. , Nunes C. M. , Keid L. B. , Hiramoto R. M. , Ferreira H. L. , Oliveira T. M. F. S. , Ovallos F. G. , Galati E. A. B. , Villegas T. J. , Bortoletto D. V. , Valadas S. Y. O. B. , Soares R. M. 
Published: January 2018

AbstractAlthough a national programme for control of visceral leishmaniosis (VL) is being run in Brazil, the disease continues to spread. This programme is essentially based on culling infected dogs from endemic regions. Thus, there is an urgent need to develop other control measures against VL to deter its advance. Here, a subunit vaccine, a recombinant vaccine, an insecticide-impregnated collar and the associations between these measures were evaluated for reducing the incidence of Leishmania infection in dogs. This was through a cohort study conducted in an endemic region of Brazil, considering the incidence and time of total exposure over a period of 1 year. The incidence of VL was estimated by means of serological and molecular diagnostic tests, 180 and 360 days after the application of the control measures. The estimates of the effectiveness (EF) were not significant in any cohort. The EF of the subunit vaccine, the recombinant vaccine and the collar were 26.4%, 32.8% and 57.7% and the upper limit of the 95% confidence interval for EF were 63.7%, 67.9% and 82.5%, respectively. In conclusion, under the conditions of this study, none of the immunogens for VL control was sufficiently effective to protect dogs against infection. On the other hand, use of collars impregnated with insecticide seems to constitute a method with better prognosis, corroborating other studies in this field.
The reports of expunction are grossly exaggerated: a reply to Robert Klee
Authors: Ćirković Milan M. 
Published: January 2018

AbstractRecent paper by Robert Klee in this journal argues that we should endorse a form of cosmic pessimism due to the inevitable destruction of Earth and humanity, allegedly meaning the complete and total annihilation of all traces of humanity's existence (‘human expunction’). It could be shown that both the physical basis and philosophical methodology used by Klee to reach those bleak conclusions are at best premature and at worst unwarranted and misleading. Even worse, they reflect a mindset of unjustified and narrow-minded technological and societal pessimism, which contributes to the erosion of the Enlightenment values, the loss of public interest in space research and colonization, and could indeed increase vulnerability to real – as opposed to uncertain eschatological – global risks humanity is facing in this millennium.
The unity, diversity and conformity of bugs (Hemiptera) through time
Authors: Szwedo Jacek 
Published: January 2018

ABSTRACTThis paper outlines and discusses the fossil record of the Hemiptera – the fifth most diverse insect order. The diversity of these insects in comparison with the “Big Four” group is given, together with a short history of its classification. Updated information is presented about the fossil record of particular families, with a brief analysis. The main evolutionary traits of the major Hemiptera lineages are briefly described. The influence of biotic interactions with endosymbionts, shaping the evolution of the hemipterans as well as abiotic events and major global changes, is disputed. The innovations and perils of the evolutionary history of the Hemiptera are presented.
MicroRNA-146a-5p attenuates irradiation-induced and LPS-induced hepatic stellate cell activation and hepatocyte apoptosis through inhibition of TLR4 pathway
Authors: Chen Yuhan , Wu Zhifeng , Yuan Baoying , Dong Yinying , Zhang Li , Zeng Zhaochong 
Published: January 2018

AbstractElevated toll-like receptor 4 (TLR4) expression is associated with a high risk of radiation-induced liver disease (RILD). MicroRNA (miR)-146a-5p is a key regulator of lipopolysaccharide (LPS)/TLR4 signaling, but its role in modulation of RILD remains unclear. Here, we found that irradiation and LPS stimulation induced TLR4 and miR-146a-5p expression in the human hepatic stellate cell (HSC) line LX2. Ectopic expression of miR-146a-5p in LX2 inhibited irradiation-induced and LPS-induced pro-inflammatory cytokine secretion and cell proliferation, and promoted cell apoptosis by down-regulating the expression levels of TLR4, interleukin-1 receptor associated kinase 1 (IRAK1), tumor necrosis factor receptor associated factor 6 (TRAF6) and phosphorylation of nuclear factor-kappa B. In addition, the culture medium from the irradiated and LPS-stimulated HSCs transfected with miR-146a-5p significantly attenuated apoptosis in irradiated hepatocytes. Overexpression of miR-146a-5p reduced α-smooth muscle actin production in irradiated and LPS-stimulated LX2 cells, which was associated with inhibition of TRAF6-mediated JNK and Smad2 phosphorylation. Knockdown of TRAF6 or IRAK1 mimicked the effects of miR-146a-5p on HSC function. Furthermore, miR-146a-5p treatment alleviated irradiation-induced and endotoxin-induced hepatic inflammatory response and fibrogenesis in mice through inhibition of the TLR4 signaling pathway. Collectively, this study reveals the anti-pro-inflammatory and anti-fibrotic effects of miR-146a-5p on liver injury, and suggests a potential application of miR-146a-5p in the therapeutic prevention of RILD.
AMP-activated protein kinase agonist N6-(3-hydroxyphenyl)adenosine protects against fulminant hepatitis by suppressing inflammation and apoptosis
Authors: Li Jin , Chen Bo , Zhong Liping , Gao Feng , Zhu Haibo , Wang Fengzhong 
Published: January 2018

AbstractBoth AMP-activated protein kinase (AMPK) agonist and inhibitor have been reported to protect against fulminant hepatitis, implying that AMPK may play a complicated role in the development of fulminant hepatitis. In this study, we exploited whether the novel AMPK agonist N6-(3-hydroxyphenyl)adenosine (named as M1) exerted protective effects on fulminant hepatitis and whether its beneficial effects were AMPK-dependent. Results showed that intraperitoneal injection of M1 improved liver function, ameliorated liver injury and finally raised the survival rate in d-galactosamine/lipopolysaccharide (GalN/LPS)-treated mice. These beneficial effects of M1 may attribute to the suppression of pro-inflammatory cytokines production and the prevention of hepatocyte apoptosis. Furthermore, M1 pretreatment mitigated LPS-stimulated TLR4 expression and NFκB activation in murine peritoneal macrophages and prevented actinomycin D (Act D)/tumor necrosis factor α (TNFα)-induced apoptosis by promoting protective autophagy in primary hepatocytes. Additionally, M1-induced AMPK activation was responsible both for its anti-inflammatory action in macrophages and for its anti-apoptotic action in hepatocytes. To our surprise, compared with the control AMPKα1lox/lox/AMPKα2lox/lox mice, liver-specific AMPKα1 knockout (AMPKα1LS−/−) mice were more sensitive to GalN/LPS administration but not AMPKα2LS−/−mice, and the beneficial effects of M1 on acute liver failure and the production of pro-inflammatory factors were dampened in AMPKα1LS−/− mice. Therefore, our study may prove that M1 could be a promising therapeutic agent for fulminant hepatitis, and targeting AMPK may be useful therapeutically in the control of LPS-induced hepatotoxicity.
Discovery of a small-molecule protein kinase Cδ-selective activator with promising application in colon cancer therapy
Authors: Bessa Cláudia , Soares Joana , Raimundo Liliana , Loureiro Joana B. , Gomes Célia , Reis Flávio , Soares Miguel L. , Santos Daniel , Dureja Chetna , Chaudhuri Saumya R. , Lopez-Haber Cynthia , Kazanietz Marcelo G. , Gonçalves Jorge , Simões Maria F. , Rijo Patrícia , Saraiva Lucília 
Published: January 2018

AbstractProtein kinase C (PKC) isozymes play major roles in human diseases, including cancer. Yet, the poor understanding of isozymes-specific functions and the limited availability of selective pharmacological modulators of PKC isozymes have limited the clinical translation of PKC-targeting agents. Here, we report the first small-molecule PKCδ-selective activator, the 7α-acetoxy-6β-benzoyloxy-12-O-benzoylroyleanone (Roy-Bz), which binds to the PKCδ-C1-domain. Roy-Bz potently inhibited the proliferation of colon cancer cells by inducing a PKCδ-dependent mitochondrial apoptotic pathway involving caspase-3 activation. In HCT116 colon cancer cells, Roy-Bz specifically triggered the translocation of PKCδ but not other phorbol ester responsive PKCs. Roy-Bz caused a marked inhibition in migration of HCT116 cells in a PKCδ-dependent manner. Additionally, the impairment of colonosphere growth and formation, associated with depletion of stemness markers, indicate that Roy-Bz also targets drug-resistant cancer stem cells, preventing tumor dissemination and recurrence. Notably, in xenograft mouse models, Roy-Bz showed a PKCδ-dependent antitumor effect, through anti-proliferative, pro-apoptotic, and anti-angiogenic activities. Besides, Roy-Bz was non-genotoxic, and in vivo it had no apparent toxic side effects. Collectively, our findings reveal a novel promising anticancer drug candidate. Most importantly, Roy-Bz opens the way to a new era on PKC biology and pharmacology, contributing to the potential redefinition of the structural requirements of isozyme-selective agents, and to the re-establishment of PKC isozymes as feasible therapeutic targets in human diseases.
NDRG2 contributes to cisplatin sensitivity through modulation of BAK-to-Mcl-1 ratio
Authors: Park Soojong , Oh Sang-Seok , Lee Ki Won , Lee Yeon-Kyeong , Kim Nae Yu , Kim Joo Heon , Yoo Jiyun , Kim Kwang Dong 
Published: January 2018

AbstractThe downregulation of N-Myc downstream-regulated gene 2 (NDRG2) is known to be associated with the progression and poor prognosis of several cancers. Sensitivity to anti-cancer may be associated with a good prognosis in cancer patients, and NDRG2, which is induced by p53, sensitizes the cells to chemotherapy. However, the unique function of NDRG2 as an inducer of apoptosis under chemotreatment has not been sufficiently studied. In this study, we investigated the role of NDRG2 in chemo-sensitivity, focusing on cisplatin in U937 histiocytic lymphoma, which has the loss-of-functional mutation in p53. NDRG2 promoted the sensitivity to cisplatin through the modulation of the BAK-to-Mcl-1 ratio. The degradation of Mcl-1 and increase in BAK were mediated by JNK activation and the eIF2α/p-eIF2α pathway, respectively, which depended on PKR activation in NDRG2-overexpressed U937 (U937-NDRG2) cells. NOX5 was highly expressed in U937-NDRG2 cells and contributed to ROS production after cisplatin treatment. ROS scavenging or NOX5-knockdown successfully inhibited the sensitivity of U937-NDRG2 cells to cisplatin. Taken together, these findings indicate that NDRG2 contributed to the increased sensitivity to ciplatin through the modulation of Bak-to-Mcl-1 ratio regulated by NOX5-ROS-PKR pathway; therefore, we suggest that NDRG2 may be a molecular target for improving the efficacy of drug treatment in cancer patients.
Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae
Authors: Benjak Andrej , Avanzi Charlotte , Singh Pushpendra , Loiseau Chloé , Girma Selfu , Busso Philippe , Fontes Amanda N. Brum , Miyamoto Yuji , Namisato Masako , Bobosha Kidist , Salgado Claudio G. , da Silva Moisés B. , Bouth Raquel C. , Frade Marco A. C. , Filho Fred Bernardes , Barreto Josafá G. , Nery José A. C. , Bührer-Sékula Samira , Lupien Andréanne , Al-Samie Abdul R. , Al-Qubati Yasin , Alkubati Abdul S. , Bretzel Gisela , Vera-Cabrera Lucio , Sakho Fatoumata , Johnson Christian R. , Kodio Mamoudou , Fomba Abdoulaye , Sow Samba O. , Gado Moussa , Konaté Ousmane , Stefani Mariane M. A. , Penna Gerson O. , Suffys Philip N. , Sarno Euzenir Nunes , Moraes Milton O. , Rosa Patricia S. , Baptista Ida M. F. Dias , Spencer John S. , Aseffa Abraham , Matsuoka Masanori , Kai Masanori , Cole Stewart T. 
Published: January 2018

AbstractLeprosy is a chronic human disease caused by the yet-uncultured pathogenMycobacterium leprae. Although readily curable with multidrug therapy (MDT), over 200,000 new cases are still reported annually. Here, we obtainM. lepraegenome sequences from DNA extracted directly from patients’ skin biopsies using a customized protocol. Comparative and phylogenetic analysis of 154 genomes from 25 countries provides insight into evolution and antimicrobial resistance, uncovering lineages and phylogeographic trends, with the most ancestral strains linked to the Far East. In addition to known MDT-resistance mutations, we detect other mutations associated with antibiotic resistance, and retrace a potential stepwise emergence of extensive drug resistance in the pre-MDT era. Some of the previously undescribed mutations occur in genes that are apparently subject to positive selection, and two of these (ribD,fadD9) are restricted to drug-resistant strains. Finally, nonsense mutations in thenthexcision repair gene are associated with greater sequence diversity and drug resistance.
Double-layered protein nanoparticles induce broad protection against divergent influenza A viruses
Authors: Deng Lei , Mohan Teena , Chang Timothy Z. , Gonzalez Gilbert X. , Wang Ye , Kwon Young-Man , Kang Sang-Moo , Compans Richard W. , Champion Julie A. , Wang Bao-Zhong 
Published: January 2018

AbstractCurrent influenza vaccines provide limited protection against circulating influenza A viruses. A universal influenza vaccine will eliminate the intrinsic limitations of the seasonal flu vaccines. Here we report methodology to generate double-layered protein nanoparticles as a universal influenza vaccine. Layered nanoparticles are fabricated by desolvating tetrameric M2e into protein nanoparticle cores and coating these cores by crosslinking headless HAs. Representative headless HAs of two HA phylogenetic groups are constructed and purified. Vaccinations with the resulting protein nanoparticles in mice induces robust long-lasting immunity, fully protecting the mice against challenges by divergent influenza A viruses of the same group or both groups. The results demonstrate the importance of incorporating both structure-stabilized HA stalk domains and M2e into a universal influenza vaccine to improve its protective potency and breadth. These potent disassemblable protein nanoparticles indicate a wide application in protein drug delivery and controlled release.
T cells specific for post-translational modifications escape intrathymic tolerance induction
Authors: Raposo Bruno , Merky Patrick , Lundqvist Christina , Yamada Hisakata , Urbonaviciute Vilma , Niaudet Colin , Viljanen Johan , Kihlberg Jan , Kyewski Bruno , Ekwall Olov , Holmdahl Rikard , Bäcklund Johan 
Published: January 2018

AbstractEstablishing effective central tolerance requires the promiscuous expression of tissue-restricted antigens by medullary thymic epithelial cells. However, whether central tolerance also extends to post-translationally modified proteins is not clear. Here we show a mouse model of autoimmunity in which disease development is dependent on post-translational modification (PTM) of the tissue-restricted self-antigen collagen type II. T cells specific for the non-modified antigen undergo efficient central tolerance. By contrast, PTM-reactive T cells escape thymic selection, though the PTM variant constitutes the dominant form in the periphery. This finding implies that the PTM protein is absent in the thymus, or present at concentrations insufficient to induce negative selection of developing thymocytes and explains the lower level of tolerance induction against the PTM antigen. As the majority of self-antigens are post-translationally modified, these data raise the possibility that T cells specific for other self-antigens naturally subjected to PTM may escape central tolerance induction by a similar mechanism.
Shielding and activation of a viral membrane fusion protein
Authors: Halldorsson Steinar , Li Sai , Li Mengqiu , Harlos Karl , Bowden Thomas A. , Huiskonen Juha T. 
Published: January 2018

AbstractEntry of enveloped viruses relies on insertion of hydrophobic residues of the viral fusion protein into the host cell membrane. However, the intermediate conformations during fusion remain unknown. Here, we address the fusion mechanism of Rift Valley fever virus. We determine the crystal structure of the Gn glycoprotein and fit it with the Gc fusion protein into cryo-electron microscopy reconstructions of the virion. Our analysis reveals how the Gn shields the hydrophobic fusion loops of the Gc, preventing premature fusion. Electron cryotomography of virions interacting with membranes under acidic conditions reveals how the fusogenic Gc is activated upon removal of the Gn shield. Repositioning of the Gn allows extension of Gc and insertion of fusion loops in the outer leaflet of the target membrane. These data show early structural transitions that enveloped viruses undergo during host cell entry and indicate that analogous shielding mechanisms are utilized across diverse virus families.
Pregnancy and infection: using disease pathogenesis to inform vaccine strategy
Authors: Vermillion Meghan S. , Klein Sabra L. 
Published: January 2018

AbstractVaccination is the mainstay of preventative medicine for many infectious diseases. Pregnant women, unborn fetuses, and neonates represent three at-risk populations that can be simultaneously protected by strategic vaccination protocols. Because the pathogenesis of different infectious microbes varies based on tissue tropism, timing of infection, and host susceptibility, the goals of immunization are not uniform across all vaccines. Mechanistic understanding of infectious disease pathogenesis and immune responses is therefore essential to inform vaccine design and the implementation of appropriate immunization protocols that optimize protection of pregnant women, fetuses, and neonates.
Novel insights on new particle formation derived from a pan-european observing system
Authors: Dall’Osto M. , Beddows D. C. S. , Asmi A. , Poulain L. , Hao L. , Freney E. , Allan J. D. , Canagaratna M. , Crippa M. , Bianchi F. , de Leeuw G. , Eriksson A. , Swietlicki E. , Hansson H. C. , Henzing J. S. , Granier C. , Zemankova K. , Laj P. , Onasch T. , Prevot A. , Putaud J. P. , Sellegri K. , Vidal M. , Virtanen A. , Simo R. , Worsnop D. , O’Dowd C. , Kulmala M. , Harrison Roy M. 
Published: January 2018

AbstractThe formation of new atmospheric particles involves an initial step forming stable clusters less than a nanometre in size (<~1 nm), followed by growth into quasi-stable aerosol particles a few nanometres (~1–10 nm) and larger (>~10 nm). Although at times, the same species can be responsible for both processes, it is thought that more generally each step comprises differing chemical contributors. Here, we present a novel analysis of measurements from a unique multi-station ground-based observing system which reveals new insights into continental-scale patterns associated with new particle formation. Statistical cluster analysis of this unique 2-year multi-station dataset comprising size distribution and chemical composition reveals that across Europe, there are different major seasonal trends depending on geographical location, concomitant with diversity in nucleating species while it seems that the growth phase is dominated by organic aerosol formation. The diversity and seasonality of these events requires an advanced observing system to elucidate the key processes and species driving particle formation, along with detecting continental scale changes in aerosol formation into the future.
Characterization of Dopaminergic System in the Striatum of Young Adult Park2−/− Knockout Rats
Authors: Gemechu Jickssa M. , Sharma Akhil , Yu Dongyue , Xie Yuran , Merkel Olivia M. , Moszczynska Anna 
Published: January 2018

AbstractMutations in parkin gene (Park2) are linked to early-onset autosomal recessive Parkinson’s disease (PD) and young-onset sporadic PD. Park2 knockout (PKO) rodents; however, do not display neurodegeneration of the nigrostriatal pathway, suggesting age-dependent compensatory changes. Our goal was to examine dopaminergic (DAergic) system in the striatum of 2 month-old PKO rats in order to characterize compensatory mechanisms that may have occurred within the system. The striata form wild type (WT) and PKO Long Evans male rats were assessed for the levels of DAergic markers, for monoamine oxidase (MAO) A and B activities and levels, and for the levels of their respective preferred substrates, serotonin (5-HT) and ß-phenylethylamine (ß-PEA). The PKO rats displayed lower activities of MAOs and higher levels of ß-PEA in the striatum than their WT counterparts. Decreased levels of ß-PEA receptor, trace amine-associated receptor 1 (TAAR-1), and postsynaptic DA D2 (D2L) receptor accompanied these alterations. Drug-naive PKO rats displayed normal locomotor activity; however, they displayed decreased locomotor response to a low dose of psychostimulant methamphetamine, suggesting altered DAergic neurotransmission in the striatum when challenged with an indirect agonist. Altogether, our findings suggest that 2 month-old PKO male rats have altered DAergic and trace aminergic signaling.