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Structural and functional aspects of the Helicobacter pylori secretome

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World Journal of Gastroenterology 2014年第6期20卷 1402-1423页

作者： Giuseppe Zanotti laura Cendron Department of Biomedical Sciences University of Padua Department of Biology University of Padua

Proteins secreted by Helicobacter pylori (H. pylori), an important human pathogen responsible for severe gastric diseases, are reviewed from the point of view of their biochemical characterization, both functional and structural. Despite the vast amount of experimental data available on the proteins secreted by this bacterium, the precise size of the secretome remains unknown. In this review, we consider as secreted both proteins that contain a secretion signal for the periplasm and proteins that have been detected in the external medium in in vitro experiments. In this way, H. pylori’s secretome appears to be composed of slightly more than 160 proteins, but this number must be considered very cautiously, not only because the definition of secretome itself is ambiguous but also because the included proteins were observed as secreted in in vitro experiments that were not representative of the environmental situation in vivo. The proteins that appear to be secreted can be grouped into different classes: enzymes (48 proteins), outer membrane proteins (43), components of flagella (11), members of the cytotoxic-associated genes pathogenicity island or other toxins (8 and 5, respectively), binding and transport proteins (9), and others (11). A final group, which includes 28 members, is represented by hypothetical uncharacterized proteins. Despite the large amount of data accumulated on the H. pylori secretome, a considerable amount of work remains to reach a full comprehension of the system at the molecular level.

关键词： Helicobacter pylori Secreted proteins Periplasmic space Secretion signal Secretome

Implications of metabolism-driven myeloid dysfunctions in cancer therapy

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Cellular & Molecular Immunology 2021年第4期18卷 829-841页

作者： laura Strauss Valentina Guarneri Alessandra Gennari Antonio Sica Department of Immunopharmacology and Immuno Oncology EMD Serono Research&Development InstituteInc.80119545A Middlesex TurnpikeBillericaMA 01821USA Department of Surgery Oncology and GastroenterologyUniversity of PadovaPadovaItaly Veneto Institute of Oncology-IRCCS PaduaItalyPadovaItaly Division of Oncology Department of Translational MedicineUniversity of Eastern PiedmontNovaraItaly Department of Pharmaceutical Sciences University of Eastern PiedmontA.Avogadrovia Bovio 6NovaraItaly Humanitas Clinical and Research Center IRCCSVia Manzoni 56RozzanoMilanItaly

Immune homeostasis is maintained by an adequate balance of myeloid and lymphoid *** chronic inflammatory states,including cancer,this balance is lost due to dramatic expansion of myeloid progenitors that fail to mature to functional inflammatory neutrophils,macrophages,and dendritic cells(DCs),thus giving rise to a decline in the antitumor effector lymphoid ***-related inflammation orchestrates the production of hematopoietic growth factors and cytokines that perpetuate recruitment and activation of myeloid precursors,resulting in unresolved and chronic *** pathologic inflammation creates profound alterations in the intrinsic cellular metabolism of the myeloid progenitor pool,which is amplified by competition for essential nutrients and by hypoxia-induced metabolic rewiring at the tumor ***,persistent myelopoiesis and metabolic dysfunctions contribute to the development of cancer,as well as to the severity of a broad range of diseases,including metabolic syndrome and autoimmune and infectious *** aims of this review are to(1)define the metabolic networks implicated in aberrant myelopoiesis observed in cancer patients,(2)discuss the mechanisms underlying these clinical manifestations and the impact of metabolic perturbations on clinical outcomes,and(3)explore new biomarkers and therapeutic strategies to restore immunometabolism and differentiation of myeloid cells towards an effector phenotype to increase host antitumor *** propose that the profound metabolic alterations and associated transcriptional changes triggered by chronic and overactivated immune responses in myeloid cells represent critical factors influencing the balance between therapeutic efficacy and immune-related adverse effects(irAEs)for current therapeutic strategies,including immune checkpoint inhibitor(ICI)therapy.

关键词： Myelopoiesis Tumor-associated macrophages Myeloid-derived suppressor cells Metabolism Cancer therapy

Longitudinal bending stiffness does not affect running economy in Nike Vaporfly Shoes

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Journal of Sport and Health Science 2022年第3期11卷 285-292页

作者： laura A.Healey Wouter Hoogkamer Integrative Locomotion Laboratory Department of KinesiologyUniversity of MassachusettsAmherstMA 01003-9258USA

Purpose This study aimed to determine the independent effect of the curved carbon-fiber plate in the Nike Vaporfly 4%shoe on running economy and running *** Fifteen healthy male runners completed a metabolic protocol and a biomechanics *** both protocols participants wore 2 different shoes,an intact Nike Vaporfly 4%(VF_(intact))and a cut Nike Vaporfly 4%(VF_(cut)).The VF_(cut) had 6 medio-lateral cuts through the carbon-fiber plate in the forefoot to reduce the effectiveness of the *** the metabolic protocol,participants ran at 14 km/h for 5 min,twice with each shoe,on a force-measuring treadmill while we measured metabolic *** the biomechanics protocol,participants ran across a runway with embedded force plates at 14 km/*** calculated running economy,kinetics,and lower limb joint *** Running economy did not significantly differ between shoe conditions(on average,0.55%±1.77%(mean±SD))worse in the VF_(cut) compared to the VF_(intact);95%confidence interval(-1.44%to 0.40%).Biomechanical differences were only found in the metatarsophalangeal(MTP)joint with increased MTP dorsiflexion angle,angular velocity,and negative power in the VF_(cut).Contact time was 1%longer in the VF_(intact).Conclusion Cutting the carbon-fiber plate and reducing the longitudinal bending stiffness did not have a significant effect on the energy savings in the Nike Vaporfly 4%.This suggests that the plate's stiffening effect on the MTP joint plays a limited role in the reported energy savings,and instead savings are likely from a combination and interaction of the foam,geometry,and plate.

关键词： Biomechanics Footwear Mechanical doping Metabolic rate Performance

Therapeutic potential of α7 nicotinic receptor agonists to regulate neuroinflammation in neurodegenerative diseases

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Neural Regeneration Research 2017年第9期12卷 1418-1421页

作者： laura Foucault-Fruchard Daniel Antier UMR INSERM U930 Université Fran?ois Rabelais CHRU de Tours H?pital Bretonneau

Neurodegenerative diseases, such as Alzheimer＇s, Parkinson＇s and Huntington＇s diseases, are all character- ized by a component of innate immunity called neuroinflammation. Neuronal loss and neuroinflammation are two phenomena closely linked. Hence, the neuroinflammation is a relevant target for the management of the neurodegenerative diseases given that, to date, there is no treatment to stop neuronal loss. Several studies have investigated the potential effects of activators of alpha 7 nicotinic acetylcholine receptors in animal models of neurodegenerative diseases. These receptors are widely distributed in the central nervous system. After activation, they seem to mediate the cholinergic anti-inflammatory pathway in the brain. This anti-inflammatory pathway, first described in periphery, regulates activation of microglial cells considered as the resident macrophage population of the central nervous system. In this article, we shortly review the agonists of the alpha 7 nicotinic acetylcholine receptors that have been evaluated in vivo and we focused on the selective positive allosteric modulators of these receptors. These compounds represent a key element to enhance receptor activity only in the presence of the endogenous agonist.

关键词： α7 nicotinic receptors cholinergic anti-inflammatory pathway Alzheimer's disease Huntington's disease Parkinson's disease neuroinflammation neurodegeneration positive allosteric modulators

The Sendai Framework for Disaster Risk Reduction and Persons with Disabilities

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International Journal of Disaster Risk Science 2015年第2期6卷 140-149页

作者： laura M.Stough Donghyun Kang Department of Educational Psychology Center on Disability and Development Texas A&M University College Station

In this paper, the Sendai Framework for Disaster Risk Reduction 2015–2030(SFDRR) is evaluated with respect to its ramifications for persons with disabilities. In the SFDRR, persons with disabilities were referenced either directly or indirectly as part of the preamble,the guiding principles, the priorities for action, and the role of stakeholders. In addition, the 2015 World Conference on Disaster Risk Reduction, during which the SFDRR was adopted, incorporated explicit recommendations toward a disability-accessible and inclusive environment not evident in previous disaster risk reduction conferences. The infusion of disability-related terms and concepts such as accessibility, inclusion, and universal design throughout the SFDRR document was significant. These concepts,which have their origin in disability studies, are used in the SFDRR document to refer to the needs of all in disaster,not only to people with disabilities. These disability-related concepts will now serve the field of disaster risk reduction as important overarching disaster-related principles. The authors conclude that the SFDRR has firmly established people with disabilities and their advocacy organizations as legitimate stakeholders and actors in the design and implementation of international disaster risk reduction policies.

关键词： Disabilities International policy Sendai framework for disaster risk reduction World conference on disaster risk reduction

The intestinal epithelial response to damage

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Science China(Life Sciences) 2018年第10期61卷 1205-1211页

作者： laura Weichselbaum Ophir D.Klein Program in Craniofacial Biology and Department of Orofacial Sciences University of CaliforniaSan Francisco CA 94143USA Institute for Medical Immunology Université Libre de BruxellesGosselies 6041Belgium Laboratory of Experimental Gastroenterology Université libre de BruxellesBrussels 1070Belgium Department of Pediatrics and Institute for Human Genetics University of CaliforniaSan FranciscoCA 94143 USA

The constant renewal of the intestinal epithelium is fueled by intestinal stem cells(ISCs) lying at the base of crypts, and these ISCs continuously give rise to transit-amplifying progenitor cells during homeostasis. Upon injury and loss of ISCs, the epithelium has the ability to regenerate by the dedifferentiation of progenitor cells that then regain stemness and repopulate the pool of ISCs. Epithelial cells receive cues from immune cells, mesenchymal cells and the microbiome to maintain *** review focuses on the response of the epithelium to damage and the interplay between the different intestinal compartments.

关键词： intestine regeneration microenvironment

Collecting Ophiocordyceps sinensis:an emerging livelihood strategy in the Garhwal,Indian Himalaya

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Journal of Mountain Science 2017年第2期14卷 390-402页

作者： laura CAPLINS Sarah J.HALVORSON Department of Society and Conservation College of Forestry and ConservationUniversity of MontanaMissoulaMontana59812USA Department of Geography College of Arts and SciencesUniversity of MontanaMissoulaMontana59812USA

In the Garhwal of Uttarakhand, India, the Bhotiya, an ethnically and culturally distinct tribal group, were historically engaged in seasonal migration(i.e. transhumance) to take advantage of scarce mountain resources and trade relations with Tibet. This livelihood practice has all but *** are adapting to these changing circumstances by engaging in the collection and sale of the valuable alpine medicinal fungus Ophiocordyceps sinensis, widely known as Cordyceps. The collection of this fungus has exploded, emerging as a lucrative yet high-risk livelihood strategy for many Bhotiya *** Bhotiyas' historic herding and trade-based interactions and knowledge of these alpine environments where Cordyceps are found uniquely positions them to access this valuable biological resource. Elsewhere in the Himalayan region, some households are earning as much as two-thirds of their income from the collection of Cordyceps; in China Cordyceps is now listed as an endangered species due to intense over-exploitation in the Tibetan *** paper seeks to fill the void in the scientific literature on the social, ecological and economic aspects of the emerging Cordyceps trade in the Garhwal. Our study investigates the socio-spatial dimensions of Cordyceps collection in the high alpine meadows. We document how a fusion of local knowledge and practice with alpine mountain systems has served to reinvigorate the economic integrity of mountain communities at a time of rapid socioeconomic change and to reimagine a new relationship between alpine resources and community *** article offers suggestions to address the sustainability of both Cordyceps collection and livelihood activities which hinge on this fungus population. We find a need for(1) community-based conservation measures that are rooted in(2) secure resource access rights for local communities to continue sustainable collection and sale of Cordyceps and(3) participatory-and science-based proc

关键词： Cordyceps ( Ophiocordyceps sinensis) Garhwal Himalaya Livelihood Alpine meadows Bhotiya Sustainability

Consistent individual differences in fathering in threespined stickleback Gasterosteus aculeatus

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Current Zoology 2012年第1期58卷 45-52页

作者： laura R Stein Alison M Bell Department of Animal Biology University of Illinois Urbana-Champaign Urbana IL 61801 USA.

There is growing evidence that individual animals show consistent differences in behavior. For example, individual threespined stickleback fish differ in how they react to predators and how aggressive they are during social interactions with con- specifics. A relatively unexplored but potentially important axis of variation is parental behavior. In sticklebacks, fathers provide all of the parental care that is necessary for offspring survival; therefore paternal care is directly tied to fitness. In this study, we assessed whether individual male sticklebacks differ consistently from each other in parental behavior. We recorded visits to nest, total time fanning, and activity levels of 11 individual males every day throughout one clutch, and then allowed the males to breed again. Half of the males were exposed to predation risk while parenting during the first clutch, and the other half of the males ex- perienced predation risk during the second clutch. We detected dranlatic temporal changes in parental behaviors over the course of the clutch： for example, total time fanning increased six-fold prior to eggs hatching, then decreased to approximately zero. De- spite these temporal changes, males retained their individually-distinctive parenting styles within a clutch that could not be ex- plained by differences in body size or egg mass. Moreover, individual differences in parenting were maintained when males re- produced for a second time. Males that were exposed to simulated predation risk briefly decreased fanning and increased activity levels. Altogether, these results show that individual sticklebacks consistently differ from each other in how they behave as parents [Current Zoology 58 （1）： 45-52, 2012].

关键词： Paternal care Personality Behavioral syndrome Fathers Temperament Antipredator behavior

Telecentres in Mountain Regions-A Peruvian Case Study of the Impact of Information and Communication Technologies on Remoteness and Exclusion

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Journal of Mountain Science 2009年第4期6卷 320-330页

作者： Richard Heeks laura León Kanashiro Centre for Development Informatics Arthur Lewis BuildingUniversity of Manchester

Communities in developing country mountain areas,in part due to their remoteness,find themselves excluded from social,political and economic systems; and excluded from access to resources. This paper aims to study the impact of information and communication technologies (ICTs) on remoteness and exclusion. It utilises two models - the resource movement framework,and the "information chain" - to analyse a telecentre in one district of mountainous Huancavelica,Peru's poorest region,set in the high Andes. It finds ICTs enabling new and positive resource flows for the two key user groups:teenaged school students and young farmers. These help to maintain social networks. They also support information searches that have improved agricultural practice where other information chain resources have been available. But non-use and ineffective use of the telecentre are found where information chain resources are lacking. ICTs have some impacts on intangible elements of remoteness. In this particular example,they also offer access to some previously-excluded resources. But they have not really addressed the systematic exclusions faced by mountain communities. And they so far appear to be a technology of inequality; favouring those residents who begin with better resource *** paper concludes by offering some recommendations for mountain ICT project practice.

关键词： Exclusion Telecentre Information and communication technologies (ICTs) New technology Andes Peru