bluuebunny/crossref_metadata_2025 huggingface dataset:
Addressing inequities in access to primary health care: lessons for the training of health care professionals from a regional medical school
Authors: Larkins Sarah , Sen Gupta Tarun , Evans Rebecca , Murray Richard , Preston Robyn
Published: November 2011

Attention to the inequitable distribution and limited access to primary health care resources is key to addressing the priority health needs of underserved populations in rural, remote and outer metropolitan areas. There is little high-quality evidence about improving access to quality primary health care services for underserved groups, particularly in relation to geographic barriers, and limited discussion about the training implications of reforms to improve access. To progress equity in access to primary health care services, health professional education institutions need to work with both the health sector and policy makers to address issues of workforce mix, recruitment and retention, and new models of primary health care delivery. This requires a fundamental shift in focus from these institutions and the health sector, to each view themselves as partners in an integrated teaching, research and service-oriented health system. This paper discusses the challenges and opportunities for primary health care professionals, educators and the health sector in providing quality teaching and clinical experiences for increasing numbers of health professionals as a result of the reform agenda. It then outlines some practical strategies based on theory and evolving experience for dealing with some of these challenges and capitalising on opportunities.
Are the national preventive health initiatives likely to reduce health inequities?
Authors: Baum Fran , Fisher Matthew
Published: November 2011

This paper examines commitments to address health inequities within current (2008–11) Australian government initiatives on health promotion and chronic disease prevention. Specifically, the paper considers: the Council of Australian Governments’ ‘National partnership agreement on preventive health’; the National Preventative Health Taskforce report, ‘Australia: the healthiest country by 2020’; and the Australian Government’s response to the taskforce report, ‘Taking preventative action’. Arising from these is the recent establishment of the Australian National Preventive Health Agency. Together, these measures represent a substantial public investment in health promotion and disease prevention. The present paper finds that these initiatives clearly acknowledge significantly worse health outcomes for those subject to social or economic disadvantage, and contain measures aimed to improve health outcomes among Indigenous people and those in low socioeconomic status communities. However, we argue that, as a whole, these initiatives have (thus far) largely missed an opportunity to develop a whole of government approach to health promotion able to address upstream social determinants of health and health inequities in Australia. In particular, they are limited by a primary focus on individual health behaviours as risk factors for chronic disease, with too little attention on the wider socioeconomic and cultural factors that drive behaviours, and so disease outcomes, in populations.
'Community navigators': making a difference by promoting health in culturally and linguistically diverse (CALD) communities in Logan, Queensland
Authors: Henderson Saras , Kendall Elizabeth
Published: November 2011

A key component of the 2011 Australian National Health Reform, via the Access and Equity Policy, is to improve access to quality health services for all Australians including CALD communities. Awareness has been raised that certain CALD communities in Australia experience limited access to health care and services, resulting in poor health outcomes. To address this issue, the Community Navigator Model was developed and implemented in four CALD communities in Logan, Queensland, through a partnership between government and non-government organisations. The model draws on local natural leaders selected by community members who then act as a conduit between the community and health service providers. Nine ‘navigators’ were selected from communities with low service access including the Sudanese, Burmese, Afghan and Pacific Islander communities. The navigators were trained and employed at one of two local non-government organisations. The navigators’ role included assessing client needs, facilitating health promotion, supporting community members to access health services, supporting general practitioners (GPs) to use interpreters and making referrals to health services. This paper explores the ‘lived experience’ of the navigators using a phenomenological approach. The findings revealed three common themes, namely: (1) commitment to an altruistic attitude of servility allowing limitless community access to their services; (2) becoming knowledge brokers, with a focus on the social determinants of health; and (3) ‘walking the walk’ to build capacity and achieving health outcomes for the community. These themes revealed the extent to which the role of CALD community navigators has the potential to make a difference to health equity in these communities, thus contributing to the Australian National Health Reform.
Equity of colorectal cancer screening: which groups have inequitable participation and what can we do about it?
Authors: Ward Paul R. , Javanparast Sara , Wilson Carlene
Published: November 2011

The National Bowel Cancer Screening Program (NBCSP) offers population-based screening for colorectal cancer (CRC) across Australia. The aims of this paper were to highlight the inequities in CRC screening in South Australia (SA) and the system-related barriers and enablers to CRC screening from the perspective of participants identified as having inequitable participation. First, de-identified data for the SA population of the NBCSP were statistically analysed and then mapped. Second, 117 in-depth interviews were conducted with culturally and linguistically diverse (CALD) groups, Indigenous and Anglo-Saxon Australians. Participation rates in the NBCSP were geographically and statistically significantly different (P < 0.0001) on the basis of gender (higher for women), age (higher for older people) and socioeconomic status (higher for more affluent people). The main system-related barriers were the lack of awareness of CRC or CRC screening within these groups, the problems with language due to most of the information being in English and the lack of recommendation by a doctor. This study revealed that inequity exists in the NBCSP participation in SA, and we identified both barriers and facilitators to CRC screening that require action at the level of both policy and practice. There is a large role in primary health care of both recommending CRC screening and facilitating equitable participation.
Working in partnership with vulnerable families: the experience of child and family health practitioners
Authors: Rossiter Chris , Fowler Cathrine , Hopwood Nick , Lee Alison , Dunston Roger
Published: November 2011

Family circumstances in infancy are persistent and powerful determinants of children’s physical and mental health, influencing inequalities that trace from childhood through to adulthood. While the social factors that perpetuate patterns of inequality are more complex than can be addressed through single interventions, child and family health (CFH) services represent crucial sites where trajectories of inequality can be disrupted. In particular, approaches that foster opportunities for practitioner–parent engagement that challenge traditional hierarchical health care practice, such as the Family Partnership Model (FPM), are recommended as ways of addressing disadvantage. Little is known about how practitioners implement models of working in partnership with families and, consequently, there is a gap in understanding how best to develop and sustain these new CFH practices. This paper reports a research project that investigated the experiences of 25 health professionals working within a FPM framework with vulnerable families. Through discussion of four key themes – redefining expertise, changing practices, establishing new relationships with parents and the complexities of partnership practice – the paper offers first-hand accounts of reframing practices that recognise the needs, skills and expertise of parents and thus contribute to empowerment of families.
Beyond the rhetoric: how can non-government organisations contribute to reducing health disparities for Aboriginal and Torres Strait Islander people?
Authors: Wood Lisa , Shilton Trevor , Dimer Lyn , Smith Julie , Leahy Timothy
Published: November 2011

The prevailing disparities in Aboriginal health in Australia are a sobering reminder of failed health reforms, compounded by inadequate attention to the social determinants shaping health and well-being. Discourse around health reform often focuses on the role of government, health professionals and health institutions. However, not-for-profit health organisations are also playing an increasing role in health policy, research and program delivery across the prevention to treatment spectrum. This paper describes the journey of the National Heart Foundation of Australia in West Australia (Heart Foundation WA hereafter) with Aboriginal employees and the Aboriginal community in taking a more proactive role in reducing Aboriginal health disparities, focusing in particular on lessons learnt that are applicable to other non-government organisations. Although the Heart Foundation WA has employed and worked with Aboriginal people and has long identified the Aboriginal community as a priority population, recent years have seen greater embedding of this within its organisational culture, governance, policies and programs. In turn, this has shaped the organisation’s response to external health reforms and issues. Responses have included the development of an action plan to eliminate disparities of cardiovascular care in the hospital system, and collaboration and engagement with health professional groups involved in delivery of care to Aboriginal people. Examples of governance measures are also described in this paper. Although strategies and the lessons learnt have been in the context of cardiovascular health disparities, they are applicable to other organisations across the health sector. Moreover, the most powerful lesson learnt is universal in its relevance; individual programs, policies and reforms are more likely to succeed when they are underpinned by whole of organisation ownership and internalisation of the need to redress disparities in health.
Glucocorticoid therapy of antigen-induced arthritis depends on the dimerized glucocorticoid receptor in T cells
Authors: Baschant Ulrike , Frappart Lucien , Rauchhaus Una , Bruns Lisa , Reichardt Holger M. , Kamradt Thomas , Bräuer Rolf , Tuckermann Jan P.
Published: November 2011

Despite several side effects, glucocorticoids (GCs) have been widely used for 60 y to treat rheumatoid arthritis on the basis of their antiinflammatory effects. However, the cells targeted by GCs and the transcriptional mechanisms underlying their actions through the glucocorticoid receptor (GR) in steroid therapy remain poorly defined. Using cell type-specific GR-deficient mice subjected to antigen-induced arthritis (AIA) as a model of human rheumatoid arthritis, we show that GC action on T cells but not myeloid cells is critical for therapeutic intervention in AIA. Furthermore, the resistance of mice expressing a DNA binding-defective GR (GRdim) to GC treatment reveals that dimerization of the GR is indispensable for the antiinflammatory effects. In these mice, the GC-induced suppression of TH1 and TH17 cell-derived proinflammatory cytokines is impaired. Our finding that IL-17A−/−mice are resistant to GC therapy, whereas IFN-γ−/−mice respond as efficiently as WT mice implies that IL-17–producing T cells and not IFN-γ–producing T cells are the most important targets for an efficient GC therapy. The present study's identification of the critical cell type and the mode of GR action in steroid therapy of AIA significantly advances our understanding of steroid therapy and should lead to therapies with greater efficiency and fewer side effects.
Metacommunity theory explains the emergence of food web complexity
Authors: Pillai Pradeep , Gonzalez Andrew , Loreau Michel
Published: November 2011

Food webs are highly complex ecological networks, dynamic in both space and time. Metacommunity models are now at the core of unified theories of biodiversity, but to date they have not addressed food web complexity. Here we show that metacommunity theory can explain the emergence of species-rich food webs with complex network topologies. Our analysis shows that network branching in the food web is maximized at intermediate colonization rates and limited dispersal scales, which also leads to concomitant peaks in species diversity. Increased food web complexity and species diversity are made possible by the structural role played by network branches that are supported by omnivore and generalist feeding links. Thus, in contrast to traditional food web theory, which emphasizes the destabilizing effect of omnivory feeding in closed systems, metacommunity theory predicts that these feeding links, which are commonly observed in empirical food webs, play a critical structural role as food webs assemble in space. As this mechanism functions at the metacommunity level, evidence for its operation in nature will be obtained through multiscale surveys of food web structure. Finally, we apply our theory to reveal the effects of habitat destruction on network complexity and metacommunity diversity.
Frozen steady states in active systems
Authors: Schaller Volker , Weber Christoph A. , Hammerich Benjamin , Frey Erwin , Bausch Andreas R.
Published: November 2011

Even simple active systems can show a plethora of intriguing phenomena and often we find complexity where we would have expected simplicity. One striking example is the occurrence of a quiescent or absorbing state with frozen fluctuations that at first sight seems to be impossible for active matter driven by the incessant input of energy. While such states were reported for externally driven systems through macroscopic shear or agitation, the investigation of frozen active states in inherently active systems like cytoskeletal suspensions or active gels is still at large. Using high-density motility assay experiments, we demonstrate that frozen steady states can arise in active systems if active transport is coupled to growth processes. The experiments are complemented by agent-based simulations which identify the coupling between self-organization, growth, and mechanical properties to be responsible for the pattern formation process.
Transcriptomic resilience to global warming in the seagrassZostera marina, a marine foundation species
Authors: Franssen Susanne U. , Gu Jenny , Bergmann Nina , Winters Gidon , Klostermeier Ulrich C. , Rosenstiel Philip , Bornberg-Bauer Erich , Reusch Thorsten B. H.
Published: November 2011

Large-scale transcription profiling via direct cDNA sequencing provides important insights as to how foundation species cope with increasing climatic extremes predicted under global warming. Species distributed along a thermal cline, such as the ecologically important seagrassZostera marina, provide an opportunity to assess temperature effects on gene expression as a function of their long-term adaptation to heat stress. We exposed a southern and northern European population ofZostera marinafrom contrasting thermal environments to a realistic heat wave in a common-stress garden. In a fully crossed experiment, eight cDNA libraries, each comprising ∼125 000 reads, were obtained during and after a simulated heat wave, along with nonstressed control treatments. Although gene-expression patterns during stress were similar in both populations and were dominated by classical heat-shock proteins, transcription profiles diverged after the heat wave. Gene-expression patterns in southern genotypes returned to control values immediately, but genotypes from the northern site failed to recover and revealed the induction of genes involved in protein degradation, indicating failed metabolic compensation to high sea-surface temperature. We conclude that the return of gene-expression patterns during recovery provides critical information on thermal adaptation in aquatic habitats under climatic stress. As a unifying concept for ecological genomics, we propose transcriptomic resilience, analogous to ecological resilience, as an important measure to predict the tolerance of individuals and hence the fate of local populations in the face of global warming.
Direct-bandgap light-emitting germanium in tensilely strained nanomembranes
Authors: Sánchez-Pérez Jose R. , Boztug Cicek , Chen Feng , Sudradjat Faisal F. , Paskiewicz Deborah M. , Jacobson RB , Lagally Max G. , Paiella Roberto
Published: November 2011

Silicon, germanium, and related alloys, which provide the leading materials platform of electronics, are extremely inefficient light emitters because of the indirect nature of their fundamental energy bandgap. This basic materials property has so far hindered the development of group-IV photonic active devices, including diode lasers, thereby significantly limiting our ability to integrate electronic and photonic functionalities at the chip level. Here we show that Ge nanomembranes (i.e., single-crystal sheets no more than a few tens of nanometers thick) can be used to overcome this materials limitation. Theoretical studies have predicted that tensile strain in Ge lowers the direct energy bandgap relative to the indirect one. We demonstrate that mechanically stressed nanomembranes allow for the introduction of sufficient biaxial tensile strain to transform Ge into a direct-bandgap material with strongly enhanced light-emission efficiency, capable of supporting population inversion as required for providing optical gain.
Conformational lability in the class II MHC 310helix and adjacent extended strand dictate HLA-DM susceptibility and peptide exchange
Authors: Painter Corrie A. , Negroni Maria P. , Kellersberger Katherine A. , Zavala-Ruiz Zarixia , Evans James E. , Stern Lawrence J.
Published: November 2011

HLA-DM is required for efficient peptide exchange on class II MHC molecules, but its mechanism of action is controversial. We trapped an intermediate state of class II MHC HLA-DR1 by substitution of αF54, resulting in a protein with increased HLA-DM binding affinity, weakened MHC-peptide hydrogen bonding as measured by hydrogen-deuterium exchange mass spectrometry, and increased susceptibility to DM-mediated peptide exchange. Structural analysis revealed a set of concerted conformational alterations at the N-terminal end of the peptide-binding site. These results suggest that interaction with HLA-DM is driven by a conformational change of the MHC II protein in the region of the α-subunit 310helix and adjacent extended strand region, and provide a model for the mechanism of DM-mediated peptide exchange.
An antinociceptive role for substance P in acid-induced chronic muscle pain
Authors: Lin Chia-Ching John , Chen Wei-Nan , Chen Chien-Ju , Lin Yi-Wen , Zimmer Andreas , Chen Chih-Cheng
Published: November 2011

Release of substance P (SP) from nociceptive nerve fibers and activation of its receptor neurokinin 1 (NK1) are important effectors in the transmission of pain signals. Nonetheless, the role of SP in muscle pain remains unknown. Here we show that a single i.m. acid injection in mice lacking SP signaling by deletion of the tachykinin precursor 1 (
Tac1
) gene or coadministration of NK1 receptor antagonists produces long-lasting hyperalgesia rather than the transient hyperalgesia seen in control animals. The inhibitory effect of SP was found exclusively in neurons expressing acid-sensing ion channel 3, where SP enhances M-channel–like potassium currents through the NK1 receptor in a G protein-independent but tyrosine kinase-dependent manner. Furthermore, the SP signaling could alter action potential thresholds and modulate the expression of TTX-resistant sodium currents in medium-sized muscle nociceptors. Thus, i.m. SP mediates an unconventional NK1 receptor signal pathway to inhibit acid activation in muscle nociceptors, resulting in an unexpected antinociceptive effect against chronic mechanical hyperalgesia, here induced by repeated i.m. acid injection.
Oceanic islands are not sinks of biodiversity in spore-producing plants
Authors: Hutsemékers Virginie , Szövényi Péter , Shaw A. Jonathan , González-Mancebo Juana-María , Muñoz Jesús , Vanderpoorten Alain
Published: November 2011

Islands have traditionally been considered as migratory and evolutionary dead ends for two main reasons: island colonizers are typically assumed to lose their dispersal power, and continental back colonization has been regarded as unlikely because of niche preemption. The hypothesis that islands might actually represent dynamic refugia and migratory stepping stones for species that are effective dispersers, and in particular, for spore-producing plants, is formally tested here, using the archipelagos of the Azores, Canary Islands, and Madeira, as a model. Population genetic analyses based on nuclear microsatellite variation indicate that dispersal ability of the mossPlatyhypnidium riparioidesdoes not decrease in the island setting. The analyses further show that, unlike island populations, mainland (southwestern Europe and North Africa) populations underwent a severe bottleneck during the last glacial maximum (LGM). Our results thus refute the traditional view of islands as the end of the colonization road and point to a different perception of North Atlantic archipelagos as major sources of biodiversity for the postglacial recolonization of Europe by spore-producing plants.
Temporally structured metapopulation dynamics and persistence of influenza A H3N2 virus in humans
Authors: Bahl Justin , Nelson Martha I. , Chan Kwok H. , Chen Rubing , Vijaykrishna Dhanasekaran , Halpin Rebecca A. , Stockwell Timothy B. , Lin Xudong , Wentworth David E. , Ghedin Elodie , Guan Yi , Peiris J. S. Malik , Riley Steven , Rambaut Andrew , Holmes Edward C. , Smith Gavin J. D.
Published: November 2011

Populations of seasonal influenza virus experience strong annual bottlenecks that pose a considerable extinction risk. It has been suggested that an influenza source population located in tropical Southeast or East Asia seeds annual temperate epidemics. Here we investigate the seasonal dynamics and migration patterns of influenza A H3N2 virus by analysis of virus samples obtained from 2003 to 2006 from Australia, Europe, Japan, New York, New Zealand, Southeast Asia, and newly sequenced viruses from Hong Kong. In contrast to annual temperate epidemics, relatively low levels of relative genetic diversity and no seasonal fluctuations characterized virus populations in tropical Southeast Asia and Hong Kong. Bayesian phylogeographic analysis using discrete temporal and spatial characters reveal high rates of viral migration between urban centers tested. Although the virus population that migrated between Southeast Asia and Hong Kong persisted through time, this was dependent on virus input from temperate regions and these tropical regions did not maintain a source for annual H3N2 influenza epidemics. We further show that multiple lineages may seed annual influenza epidemics, and that each region may function as a potential source population. We therefore propose that the global persistence of H3N2 influenza A virus is the result of a migrating metapopulation in which multiple different localities may seed seasonal epidemics in temperate regions in a given year. Such complex global migration dynamics may confound control efforts and contribute to the emergence and spread of antigenic variants and drug-resistant viruses.
Different levels of the Tripartite motif protein, Anomalies in sensory axon patterning (Asap), regulate distinct axonal projections of
Drosophila
sensory neurons
Authors: Morikawa Rei K. , Kanamori Takahiro , Yasunaga Kei-ichiro , Emoto Kazuo
Published: November 2011

The axonal projection pattern of sensory neurons typically is regulated by environmental signals, but how different sensory afferents can establish distinct projections in the same environment remains largely unknown.
Drosophila
class IV dendrite arborization (C4da) sensory neurons project subtype-specific axonal branches in the ventral nerve cord, and we show that the Tripartite motif protein, Anomalies in sensory axon patterning (Asap) is a critical determinant of the axonal projection patterns of different C4da neurons. Asap is highly expressed in C4da neurons with both ipsilateral and contralateral axonal projections, but the Asap level is low in neurons that have only ipsilateral projections. Mutations in
asap
cause a specific loss of contralateral projections, whereas overexpression of Asap induces ectopic contralateral projections in C4da neurons. We also show by biochemical and genetic analysis that Asap regulates Netrin signaling, at least in part by linking the Netrin receptor Frazzled to the downstream effector Pico. In the absence of Asap, the sensory afferent connectivity within the ventral nerve cord is disrupted, resulting in specific larval behavioral deficits. These results indicate that different levels of Asap determine distinct patterns of axonal projections of C4da neurons by modulating Netrin signaling and that the Asap-mediated axonal projection is critical for assembly of a functional sensory circuit.
Wing patterning gene redefines the mimetic history ofHeliconiusbutterflies
Authors: Hines Heather M. , Counterman Brian A. , Papa Riccardo , Albuquerque de Moura Priscila , Cardoso Marcio Z. , Linares Mauricio , Mallet James , Reed Robert D. , Jiggins Chris D. , Kronforst Marcus R. , McMillan W. Owen
Published: November 2011

The mimetic butterfliesHeliconius eratoandHeliconius melpomenehave undergone parallel radiations to form a near-identical patchwork of over 20 different wing-pattern races across the Neotropics. Previous molecular phylogenetic work on these radiations has suggested that similar but geographically disjunct color patterns arose multiple times independently in each species. The neutral markers used in these studies, however, can move freely across color pattern boundaries, and therefore might not represent the history of the adaptive traits as accurately as markers linked to color pattern genes. To assess the evolutionary histories across different loci, we compared relationships among races withinH. eratoand withinH. melpomeneusing a series of unlinked genes, genes linked to color pattern loci, andoptix, a gene recently shown to control red color-pattern variation. We found that although unlinked genes partition populations by geographic region,optixhad a different history, structuring lineages by red color patterns and supporting a single origin of red-rayed patterns within each species. Genes closely linked (80–250 kb) tooptixexhibited only weak associations with color pattern. This study empirically demonstrates the necessity of examining phenotype-determining genomic regions to understand the history of adaptive change in rapidly radiating lineages. With these refined relationships, we resolve a long-standing debate about the origins of the races within each species, supporting the hypothesis that the red-rayed Amazonian pattern evolved recently and expanded, causing disjunctions of more ancestral patterns.
Landslide-dammed paleolake perturbs marine sedimentation and drives genetic change in anadromous fish
Authors: Mackey Benjamin H. , Roering Joshua J. , Lamb Michael P.
Published: November 2011

Large bedrock landslides have been shown to modulate rates and processes of river activity by forming dams, forcing upstream aggradation of water and sediment, and generating catastrophic outburst floods. Less apparent is the effect of large landslide dams on river ecosystems and marine sedimentation. Combining analyses of 1-m resolution topographic data (acquired via airborne laser mapping) and field investigation, we present evidence for a large, landslide-dammed paleolake along the Eel River, CA. The landslide mass initiated from a high-relief, resistant outcrop which failed catastrophically, blocking the Eel River with an approximately 130-m-tall dam. Support for the resulting 55-km-long, 1.3-km
3
lake includes subtle shorelines cut into bounding terrain, deltas, and lacustrine sediments radiocarbon dated to 22.5 ka. The landslide provides an explanation for the recent genetic divergence of local anadromous (ocean-run) steelhead trout (
Oncorhynchus mykiss
) by blocking their migration route and causing gene flow between summer run and winter run reproductive ecotypes. Further, the dam arrested the prodigious flux of sediment down the Eel River; this cessation is recorded in marine sedimentary deposits as a 10-fold reduction in deposition rates of Eel-derived sediment and constitutes a rare example of a terrestrial event transmitted through the dispersal system and recorded offshore.
Socially transmitted gut microbiota protect bumble bees against an intestinal parasite
Authors: Koch Hauke , Schmid-Hempel Paul
Published: November 2011

Populations of important pollinators, such as bumble bees and honey bees, are declining at alarming rates worldwide. Parasites are likely contributing to this phenomenon. A distinct resident community of bacteria has recently been identified in bumble bees and honey bees that is not shared with related solitary bee species. We now show that the presence of these microbiota protects bee hosts against a widespread and highly virulent natural parasite (Crithidia bombi) in an experimental setting. We add further support to this antagonistic relationship from patterns found in field data. For the successful establishment of these microbiota and a protective effect, exposure to feces from nest mates was needed after pupal eclosion. Transmission of beneficial gut bacteria could therefore represent an important benefit of sociality. Our results stress the importance of considering the host microbiota as an “extended immune phenotype” in addition to the host immune system itself and provide a unique perspective to understanding bees in health and disease.
Nonlinear response of summer temperature to Holocene insolation forcing in Alaska
Authors: Clegg Benjamin F. , Kelly Ryan , Clarke Gina H. , Walker Ian R. , Hu Feng Sheng
Published: November 2011

Regional climate responses to large-scale forcings, such as precessional changes in solar irradiation and increases in anthropogenic greenhouse gases, may be nonlinear as a result of complex interactions among earth system components. Such nonlinear behaviors constitute a major source of climate “surprises” with important socioeconomic and ecological implications. Paleorecords are key for elucidating patterns and mechanisms of nonlinear responses to radiative forcing, but their utility has been greatly limited by the paucity of quantitative temperature reconstructions. Here we present Holocene July temperature reconstructions on the basis of midge analysis of sediment cores from three Alaskan lakes. Results show that summer temperatures during 10,000–5,500 calibrated years (cal) B.P. were generally lower than modern and that peak summer temperatures around 5,000 were followed by a decreasing trend toward the present. These patterns stand in stark contrast with the trend of precessional insolation, which decreased by ∼10% from 10,000 y ago to the present. Cool summers before 5,500 cal B.P. coincided with extensive summer ice cover in the western Arctic Ocean, persistence of a positive phase of the Arctic Oscillation, predominantly La Niña-like conditions, and variation in the position of the Alaskan treeline. These results illustrate nonlinear responses of summer temperatures to Holocene insolation radiative forcing in the Alaskan sub-Arctic, possibly because of state changes in the Arctic Oscillation and El Niño-Southern Oscillation and associated land–atmosphere–ocean feedbacks.
Tripartite motif 8 (TRIM8) modulates TNFα- and IL-1β–triggered NF-κB activation by targeting TAK1 for K63-linked polyubiquitination
Authors: Li Qi , Yan Jie , Mao Ai-Ping , Li Chao , Ran Yong , Shu Hong-Bing , Wang Yan-Yi
Published: November 2011

The tripartite motif (TRIM)-containing proteins are a family of proteins that have been known to be involved in divergent biological processes, including important roles in immune responses through regulating various signaling pathways. In this study, we identified a member of the TRIM family, TRIM8, as a positive regulator of tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β)–triggered NF-κB activation. Overexpression of TRIM8 activated NF-κB and potentiated TNFα- and IL-1β–induced activation of NF-κB, whereas knockdown of TRIM8 had opposite effects. Coimmunoprecipitations indicated that TRIM8 interacted with TGFβ activated kinase 1 (TAK1), a serine/threonine kinase essential for TNFα- and IL-β–induced NF-κB activation. Furthermore, we found that TRIM8 mediated K63-linked polyubiquitination of TAK1 triggered by TNFα and IL-1β. Our findings demonstrate that TRIM8 serves as a critical regulator of TNFα- and IL-1β–induced NF-κB activation by mediating K63-linked polyubiquitination of TAK1.
Ecological mechanisms underlying the sustainability of the agricultural heritage rice–fish coculture system
Authors: Xie Jian , Hu Liangliang , Tang Jianjun , Wu Xue , Li Nana , Yuan Yongge , Yang Haishui , Zhang Jiaen , Luo Shiming , Chen Xin
Published: November 2011

For centuries, traditional agricultural systems have contributed to food and livelihood security throughout the world. Recognizing the ecological legacy in the traditional agricultural systems may help us develop novel sustainable agriculture. We examine how rice–fish coculture (RF), which has been designated a “globally important agricultural heritage system,” has been maintained for over 1,200 y in south China. A field survey demonstrated that although rice yield and rice-yield stability are similar in RF and rice monoculture (RM), RF requires 68% less pesticide and 24% less chemical fertilizer than RM. A field experiment confirmed this result. We documented that a mutually beneficial relationship between rice and fish develops in RF: Fish reduce rice pests and rice favors fish by moderating the water environment. This positive relationship between rice and fish reduces the need for pesticides in RF. Our results also indicate a complementary use of nitrogen (N) between rice and fish in RF, resulting in low N fertilizer application and low N release into the environment. These findings provide unique insights into how positive interactions and complementary use of resource between species generate emergent ecosystem properties and how modern agricultural systems might be improved by exploiting synergies between species.
Imaging guided trials of the angiogenesis inhibitor sunitinib in mouse models predict efficacy in pancreatic neuroendocrine but not ductal carcinoma
Authors: Olson Peter , Chu Gerald C. , Perry Samuel R. , Nolan-Stevaux Olivier , Hanahan Douglas
Published: November 2011

Preclinical trials in mice represent a critical step in the evaluation of experimental therapeutics. Genetically engineered mouse models (GEMMs) represent a promising platform for the evaluation of drugs, particularly those targeting the tumor microenvironment. We evaluated sunitinib, an angiogenesis inhibitor that targets VEGF and PDGF receptor signaling, in two GEMMs of pancreatic cancer. Sunitinib did not reduce tumor burden in pancreatic ductal adenocarcinoma (PDAC), whereas tumor burden was reduced in the pancreatic neuroendocrine tumor (PNET) model, the latter results confirming and extending previous studies. To explore the basis for the lack of pathologic response in PDAC, we used noninvasive microbubble contrast-enhanced ultrasound imaging, which revealed that sunitinib reduced blood flow both in PDAC and in PNET, concomitant with a reduction in vessel density; nevertheless, PDAC tumors continued to grow, whereas PNET were growth impaired. These results parallel the response in humans, where sunitinib recently garnered FDA and European approval in PNET, whereas two antiangiogenic drugs failed to demonstrate efficacy in PDAC clinical trials. The demonstration of on-target activity but with discordant benefit in the PDAC and PNET GEMMs illustrates the potential value of linked preclinical and clinical trials.
Nitrosyl hydride (HNO) replaces dioxygen in nitroxygenase activity of manganese quercetin dioxygenase
Authors: Kumar Murugaeson R. , Zapata Adrian , Ramirez Alejandro J. , Bowen Sara K. , Francisco Wilson A. , Farmer Patrick J.
Published: November 2011

Quercetin dioxygenase (QDO) catalyzes the oxidation of the flavonol quercetin with dioxygen, cleaving the central heterocyclic ring and releasing CO. The QDO from
Bacillus subtilis
is unusual in that it has been shown to be active with several divalent metal cofactors such as Fe, Mn, and Co. Previous comparison of the catalytic activities suggest that Mn(II) is the preferred cofactor for this enzyme. We herein report the unprecedented substitution of nitrosyl hydride (HNO) for dioxygen in the activity of Mn-QDO, resulting in the incorporation of both N and O atoms into the product. Turnover is demonstrated by consumption of quercetin and other related substrates under anaerobic conditions in the presence of HNO-releasing compounds and the enzyme. As with dioxygenase activity, a nonenzymatic base-catalyzed reaction of quercetin with HNO is observed above pH 7, but no enhancement of this basal reactivity is found upon addition of divalent metal salts. Unique and regioselective N-containing products (
14
N/
15
N) have been characterized by MS analysis for both the enzymatic and nonenzymatic reactions. Of the several metallo-QDO enzymes examined for nitroxygenase activity under anaerobic condition, only the Mn(II) is active; the Fe(II) and Co(II) substituted enzymes show little or no activity. This result represents an enzymatic catalysis which we denote nitroxygenase activity; the unique reactivity of the Mn-QDO suggests a metal-mediated electron transfer mechanism rather than metal activation of the substrate’s inherent base-catalyzed reactivity.
Assessment of individual radionuclide distributions from the Fukushima nuclear accident covering central-east Japan
Authors: Kinoshita Norikazu , Sueki Keisuke , Sasa Kimikazu , Kitagawa Jun-ichi , Ikarashi Satoshi , Nishimura Tomohiro , Wong Ying-Shee , Satou Yukihiko , Handa Koji , Takahashi Tsutomu , Sato Masanori , Yamagata Takeyasu
Published: November 2011

A tremendous amount of radioactivity was discharged because of the damage to cooling systems of nuclear reactors in the Fukushima No. 1 nuclear power plant in March 2011. Fukushima and its adjacent prefectures were contaminated with fission products from the accident. Here, we show a geographical distribution of radioactive iodine, tellurium, and cesium in the surface soils of central-east Japan as determined by gamma-ray spectrometry. Especially in Fukushima prefecture, contaminated area spreads around Iitate and Naka-Dori for all the radionuclides we measured. Distributions of the radionuclides were affected by the physical state of each nuclide as well as geographical features. Considering meteorological conditions, it is concluded that the radioactive material transported on March 15 was the major contributor to contamination in Fukushima prefecture, whereas the radioactive material transported on March 21 was the major source in Ibaraki, Tochigi, Saitama, and Chiba prefectures and in Tokyo.
Heroin relapse requires long-term potentiation-like plasticity mediated by NMDA2b-containing receptors
Authors: Shen Haowei , Moussawi Khaled , Zhou Wenhua , Toda Shigenobu , Kalivas Peter W.
Published: November 2011

Persistent relapse to addictive drugs constitutes the most challenging problem in addiction therapy, and is linked to impaired prefrontal cortex regulation of motivated behaviors involving the nucleus accumbens. Using a rat model of heroin addiction, we show that relapse requires long-term potentiation (LTP)-like increases in synaptic strength in the prefrontal cortex projection to the nucleus accumbens. The increased synaptic strength was paralleled by dendritic spine enlargement in accumbens spiny neurons and required up-regulated surface expression of NMDA2b-containing receptors (NR2B). Accordingly, blocking NR2B before reinstating heroin-seeking prevented the induction of LTP-like changes in spine remodeling and synaptic strength, and inhibited heroin relapse. These data show that LTP-like neuroplasticity in prefrontal-accumbens synapses is initiated by NR2B stimulation and strongly contributes to heroin relapse. Moreover, the data reveal NR2B-containing NMDA receptors as a previously unexplored therapeutic target for treating heroin addiction.
Cesium-137 deposition and contamination of Japanese soils due to the Fukushima nuclear accident
Authors: Yasunari Teppei J. , Stohl Andreas , Hayano Ryugo S. , Burkhart John F. , Eckhardt Sabine , Yasunari Tetsuzo
Published: November 2011

The largest concern on the cesium-137 (
137
Cs) deposition and its soil contamination due to the emission from the Fukushima Daiichi Nuclear Power Plant (NPP) showed up after a massive quake on March 11, 2011. Cesium-137 (
137
Cs) with a half-life of 30.1 y causes the largest concerns because of its deleterious effect on agriculture and stock farming, and, thus, human life for decades. Removal of
137
Cs contaminated soils or land use limitations in areas where removal is not possible is, therefore, an urgent issue. A challenge lies in the fact that estimates of
137
Cs emissions from the Fukushima NPP are extremely uncertain, therefore, the distribution of
137
Cs in the environment is poorly constrained. Here, we estimate total
137
Cs deposition by integrating daily observations of
137
Cs deposition in each prefecture in Japan with relative deposition distribution patterns from a Lagrangian particle dispersion model, FLEXPART. We show that
137
Cs strongly contaminated the soils in large areas of eastern and northeastern Japan, whereas western Japan was sheltered by mountain ranges. The soils around Fukushima NPP and neighboring prefectures have been extensively contaminated with depositions of more than 100,000 and 10,000 MBq km
-2
, respectively. Total
137
Cs depositions over two domains: (
i
) the Japan Islands and the surrounding ocean (130–150 °E and 30–46 °N) and, (
ii
) the Japan Islands, were estimated to be more than 5.6 and 1.0 PBq, respectively. We hope our
137
Cs deposition maps will help to coordinate decontamination efforts and plan regulatory measures in Japan.
Evidence for an allosteric mechanism of substrate release from membrane-transporter accessory binding proteins
Authors: Marinelli Fabrizio , Kuhlmann Sonja I. , Grell Ernst , Kunte Hans-Jörg , Ziegler Christine , Faraldo-Gómez José D.
Published: November 2011

Numerous membrane importers rely on accessory water-soluble proteins to capture their substrates. These substrate-binding proteins (SBP) have a strong affinity for their ligands; yet, substrate release onto the low-affinity membrane transporter must occur for uptake to proceed. It is generally accepted that release is facilitated by the association of SBP and transporter, upon which the SBP adopts a conformation similar to the unliganded state, whose affinity is sufficiently reduced. Despite the appeal of this mechanism, however, direct supporting evidence is lacking. Here, we use experimental and theoretical methods to demonstrate that an allosteric mechanism of enhanced substrate release is indeed plausible. First, we report the atomic-resolution structure of apo TeaA, the SBP of the Na
+
-coupled ectoine TRAP transporter TeaBC from
Halomonas elongata
DSM2581
T
, and compare it with the substrate-bound structure previously reported. Conformational free-energy landscape calculations based upon molecular dynamics simulations are then used to dissect the mechanism that couples ectoine binding to structural change in TeaA. These insights allow us to design a triple mutation that biases TeaA toward apo-like conformations without directly perturbing the binding cleft, thus mimicking the influence of the membrane transporter. Calorimetric measurements demonstrate that the ectoine affinity of the conformationally biased triple mutant is 100-fold weaker than that of the wild type. By contrast, a control mutant predicted to be conformationally unbiased displays wild-type affinity. This work thus demonstrates that substrate release from SBPs onto their membrane transporters can be facilitated by the latter through a mechanism of allosteric modulation of the former.
Thin-slicing study of the oxytocin receptor (OXTR) gene and the evaluation and expression of the prosocial disposition
Authors: Kogan Aleksandr , Saslow Laura R. , Impett Emily A. , Oveis Christopher , Keltner Dacher , Rodrigues Saturn Sarina
Published: November 2011

Individuals who are homozygous for the G allele of the rs53576 SNP of the oxytocin receptor (OXTR) gene tend to be more prosocial than carriers of the A allele. However, little is known about how these differences manifest behaviorally and whether they are readily detectable by outside observers, both critical questions in theoretical accounts of prosociality. In the present study, we used thin-slicing methodology to test the hypotheses that (
i
) individual differences in rs53576 genotype predict how prosocial observers judge target individuals to be on the basis of brief observations of behavior, and (
ii
) that variation in targets’ nonverbal displays of affiliative cues would account for these judgment differences. In line with predictions, we found that individuals homozygous for the G allele were judged to be more prosocial than carriers of the A allele. These differences were completely accounted for by variations in the expression of affiliative cues. Thus, individual differences in rs53576 are associated with behavioral manifestations of prosociality, which ultimately guide the judgments others make about the individual.
Developmental stalling and organ-autonomous regulation of morphogenesis
Authors: Miletich Isabelle , Yu Wei-Yuan , Zhang Ruofang , Yang Kai , Caixeta de Andrade Simone , Pereira Silvia Fontes do A. , Ohazama Atsushi , Mock Orin B. , Buchner Georg , Sealby Jane , Webster Zoe , Zhao Minglian , Bei Marianna , Sharpe Paul T.
Published: November 2011

Timing of organ development during embryogenesis is coordinated such that at birth, organ and fetal size and maturity are appropriately proportioned. The extent to which local developmental timers are integrated with each other and with the signaling interactions that regulate morphogenesis to achieve this end is not understood. Using the absolute requirement for a signaling pathway activity (bone morphogenetic protein, BMP) during a critical stage of tooth development, we show that suboptimal levels of BMP signaling do not lead to abnormal morphogenesis, as suggested by mutants affecting BMP signaling, but to a 24-h stalling of the intrinsic developmental clock of the tooth. During this time, BMP levels accumulate to reach critical levels whereupon tooth development restarts, accelerates to catch up with development of the rest of the embryo and completes normal morphogenesis. This suggests that individual organs can autonomously control their developmental timing to adjust their stage of development to that of other organs. We also find that although BMP signaling is critical for the bud-to-cap transition in all teeth, levels of BMP signaling are regulated differently in multicusped teeth. We identify an interaction between two homeodomain transcription factors, Barx1 and Msx1, which is responsible for setting critical levels of BMP activity in multicusped teeth and provides evidence that correlates the levels of
Barx1
transcriptional activity with cuspal complexity. This study highlights the importance of absolute levels of signaling activity for development and illustrates remarkable self-regulation in organogenesis that ensures coordination of developmental processes such that timing is subordinate to developmental structure.