bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing wild and reintroduced populations of the threatened orchid Diuris fragrantissima (Orchidaceae) in south-eastern Australia
Authors: Duncan Michael , Moloney Paul D.
Published: October 2018

Orchids have high rates of speciation and extinction, and are over-represented on threatened species lists. Reintroductions are being used with increasing frequency as an important tool for threatened orchid recovery. The ultimate aim of these reintroductions is to create a self-sustaining population that will reduce the risk of extinction for the species. In this case study, we test the hypotheses that state transition, annual survival, and seed production rates in a reintroduced population were equivalent to those in the wild population. These hypotheses were tested using long-term demographic monitoring datasets from a wild and a reintroduced population of Diuris fragrantissima, and analysed using Bayesian multistate capture–recapture and multinomial models. The results showed that emergent plants at the reintroduction site were more likely to transition to vegetative or unobserved states, and less likely to flower in the following year, than those at the wild site. This resulted in a strong trend through time away from emergent life states at the reintroduction site. The estimated annual survival rate was >90% at the wild site, and <80% in five of the seven years at the reintroduction site. Flowering was the most frequently recorded life state at the wild site. The fate of an individual flower was not affected by site (wild or reintroduction), but an increase in rainfall increased the probability that a flower would set seed and decreased the probability that it would be browsed. The reintroduction has failed to produce a stable, sustainable, long-term population, but it has been valuable in providing information that will inform the development and improvement of future D. fragrantissima reintroductions. Improving our knowledge in these areas should increase the chances of future D. fragrantissima reintroductions being assessed as a success.
Fate of dried meat baits aimed at wild dog (Canis familiaris) control
Authors: Kreplins T. L. , Kennedy M. S. , Adams P. J. , Bateman P. W. , Dundas S. D. , Fleming P. A.
Published: October 2018

Context
Livestock predation is a worldwide phenomenon, causing financial losses and emotional strain on producers. Wild dogs (Canis familiaris) cause millions of dollars of damage to cattle, sheep and goat production in Australia every year, and despite on-going control (baiting, trapping, shooting, and fencing), they remain a significant problem for livestock producers across many pastoral and agricultural regions of Australia.

Aims
We aimed to quantify the uptake of dried meat baits by wild dogs and determine whether an olfactory lure (fish oil) could increase uptake.

Methods
Camera traps and sand pads were used to monitor bait uptake for three baiting events on two pastoral properties in the southern rangelands of Western Australia in 2016 and 2017.

Key results
Of the 337 monitored baits with a known outcome, young wild dogs (<8 months old) removed only four, three of which were covered in a fish-oil lure. In warmer months, baits were largely consumed by varanids, and in cooler months, when baits were taken it was predominantly by corvids. Varanids and corvids took more baits than expected on the basis of activity indices. Kangaroos, feral cats and wild dogs consumed significantly fewer baits than expected from their activity on camera.

Conclusions
We have no evidence that adult wild dogs removed baits, despite many opportunities to do so (wild dogs passing cameras), and fewer wild dogs took baits than expected on the basis of activity events seen on camera. Olfactory lures may have the potential to increase bait uptake by naïve individuals (i.e. young dogs), but the sample size was small.

Implications
Increasing the number of baiting events per year, trialling novel baits, and baiting during low non-target activity are some of the recommended methods that may increase bait persistence and uptake by wild dogs.
Effect of sequential video shot comprehensibility on attentional synchrony: A comparison of children and adults
Authors: Kirkorian Heather L. , Anderson Daniel R.
Published: October 2018

To comprehend edited video, viewers must infer the meaning conveyed by successive video shots (i.e., continuous video segments separated by edit points, such as camera cuts). The central question here was whether comprehension-related top-down cognitive processes drive eye movements during sequential processing of video montage. Eye movements were recorded as 4 year olds and adults (n= 62) watched a video with the same constituent shots in either normal or random sequence. The key analyses compared eye movements to constituent shots when presented in normal order with those to the same shots presented in random order. The dependent variable was attentional synchrony or the extent to which viewers looked at the same location at the same time, indicating commonality of processing the video. This was calculated as the bivariate contour ellipse area within which points of gaze fell during each video frame. Results indicated that children were more scattered in their gaze locations than adults. Viewers became more similar to each other as normal vignettes unfolded over time; this was especially true in adults and possibly reflects a growing and shared understanding of the content. Conversely, adult attentional synchrony was reduced when watching random shot sequences. Thus, attentional synchrony during normal video viewing is driven not only by salient visual features, such as movement and areas of high contrast, but also, by the unfolding sequential comprehension of video montage, especially in adults. Differences between children and adults indicate that this top-down control of eye movements while watching video changes systematically over development.
Minds and brains of media multitaskers: Current findings and future directions
Authors: Uncapher Melina R. , Wagner Anthony D.
Published: October 2018

Media and technology are ubiquitous elements of our daily lives, and their use can offer many benefits and rewards. At the same time, decisions about how individuals structure their use of media can be informed by consideration of whether, and if so how, the mind and brain are shaped by different use patterns. Here we review the growing body of research that investigates the cognitive and neural profiles of individuals who differ in the extent to which they simultaneously engage with multiple media streams, or ‟media multitasking.” While the literature is still sparse, and is marked by both convergent and divergent findings, the balance of evidence suggests that heavier media multitaskers exhibit poorer performance in a number of cognitive domains, relative to lighter media multitaskers (although many studies find no performance differences between groups). When evidence points to a relationship between media multitasking level and cognition, it is often on tasks that require or are influenced by fluctuations in sustained goal-directed attention. Given the real-world significance of such findings, further research is needed to uncover the mechanistic underpinnings of observed differences, to determine the direction of causality, to understand whether remediation efforts are needed and effective, and to determine how measurement heterogeneity relates to variable outcomes. Such efforts will ultimately inform decisions about how to minimize the potential costs and maximize the many benefits of our ever-evolving media landscape.
Two are better than one: Infant language learning from video improves in the presence of peers
Authors: Lytle Sarah Roseberry , Garcia-Sierra Adrian , Kuhl Patricia K.
Published: October 2018

Studies show that young children learn new phonemes and words from humans significantly better than from machines. However, it is not clear why learning from video is ineffective or what might be done to improve learning from a screen. The present study, conducted with 9-month-old infants, utilized a manipulation—touch screen video—which allowed infants to control presentations of foreign-language video clips. We tested the hypothesis that infant learning from a screen would be enhanced in the presence of a peer, as opposed to learning alone. Brain measures of phonetic learning and detailed analyses of interaction during learning confirm the hypothesis that social partners enhance learning, even from screens.
Maize yields over Europe may increase in spite of climate change, with an appropriate use of the genetic variability of flowering time
Authors: Parent Boris , Leclere Margot , Lacube Sébastien , Semenov Mikhail A. , Welcker Claude , Martre Pierre , Tardieu François
Published: October 2018

Significance

The consequences of climate change on European maize yields may become positive if farmers in 2050 use the decision rules they currently follow for adapting plant cycle duration and sowing dates to the diversity of environmental conditions. Experiments and simulations show that the current genetic variability of flowering time allows identifying a cycle duration that maximizes yield at every maize field in Europe. The assumption that farmers use this optimal cycle length in each site was supported by comparison with historical data. Simulated European production for 2050 was stable under the hypotheses of unchanged practices but was increased if farmers continued adopting the decision rules they currently use for adjusting sowing date and crop cycle duration to local environment.
Rapid diversification ofPseudomonas aeruginosain cystic fibrosis lung-like conditions
Authors: Schick Alana , Kassen Rees
Published: October 2018

Chronic infection of the cystic fibrosis (CF) airway by the opportunistic pathogenPseudomonas aeruginosais the leading cause of morbidity and mortality for adult CF patients. Prolonged infections are accompanied by adaptation ofP. aeruginosato the unique conditions of the CF lung environment, as well as marked diversification of the pathogen into phenotypically and genetically distinct strains that can coexist for years within a patient. Little is known, however, about the causes of this diversification and its impact on patient health. Here, we show experimentally that, consistent with ecological theory of diversification, the nutritional conditions of the CF airway can cause rapid and extensive diversification ofP. aeruginosa. Mucin, the substance responsible for the increased viscosity associated with the thick mucus layer in the CF airway, had little impact on within-population diversification but did promote divergence among populations. Furthermore, in vitro evolution recapitulated traits thought to be hallmarks of chronic infection, including reduced motility and increased biofilm formation, and the range of phenotypes observed in a collection of clinical isolates. Our results suggest that nutritional complexity and reduced dispersal can drive evolutionary diversification ofP. aeruginosaindependent of other features of the CF lung such as an active immune system or the presence of competing microbial species. We suggest that diversification, by generating extensive phenotypic and genetic variation on which selection can act, may be a key first step in the development of chronic infections.
Racial disparities in pollution exposure and employment at US industrial facilities
Authors: Ash Michael , Boyce James K.
Published: October 2018

Significance

Debate about regulation of industrial polluters often concerns a presumed trade-off between negative pollution impacts and positive employment opportunities. These arguments are especially sensitive among communities of racial/ethnic minorities, who disproportionately suffer exposure to pollution and lack access to high-quality employment. We combine US Environmental Protection Agency (EPA) data on toxics exposure with Equal Employment Opportunity Commission (EEOC) data on employment to examine how the racial/ethnic distribution of industrial employment corresponds to the distribution of exposure to air toxics emitted by the same facilities. The share of pollution risk accruing to minority groups generally exceeds their share of employment and greatly exceeds their share of higher paying jobs. In aggregate, we find no evidence that facilities that create higher pollution risk for surrounding communities provide more jobs.
Mercury isotope signatures record photic zone euxinia in the Mesoproterozoic ocean
Authors: Zheng Wang , Gilleaudeau Geoffrey J. , Kah Linda C. , Anbar Ariel D.
Published: October 2018

Significance

The occurrence of toxic H
2
S-rich water in the photic zone of the ocean, a phenomenon called photic zone euxinia (PZE), had profound negative impacts on ancient biological evolution and modern marine ecosystems. We explore the possibility of using mercury (Hg) stable isotopes as a new proxy for PZE. We found that Hg-isotope compositions in sedimentary rocks deposited under oxic versus H
2
S-rich conditions are distinguishable. The difference in Hg isotopes is most likely caused by contrasting Hg chemical behavior in response to changes in surface ocean redox states. Thus, our data demonstrate that Hg isotopes in marine sediments are a promising proxy of PZE, useful in future studies to refine our understanding on PZE and its impact on life.
Natural forcing of the North Atlantic nitrogen cycle in the Anthropocene
Authors: Wang Xingchen Tony , Cohen Anne L. , Luu Victoria , Ren Haojia , Su Zhan , Haug Gerald H. , Sigman Daniel M.
Published: October 2018

Human alteration of the global nitrogen cycle intensified over the 1900s. Model simulations suggest that large swaths of the open ocean, including the North Atlantic and the western Pacific, have already been affected by anthropogenic nitrogen through atmospheric transport and deposition. Here we report an ∼130-year-long record of the15N/14N of skeleton-bound organic matter in a coral from the outer reef of Bermuda, which provides a test of the hypothesis that anthropogenic atmospheric nitrogen has significantly augmented the nitrogen supply to the open North Atlantic surface ocean. The Bermuda15N/14N record does not show a long-term decline in the Anthropocene of the amplitude predicted by model simulations or observed in a western Pacific coral15N/14N record. Rather, the decadal variations in the Bermuda15N/14N record appear to be driven by the North Atlantic Oscillation, most likely through changes in the formation rate of Subtropical Mode Water. Given that anthropogenic nitrogen emissions have been decreasing in North America since the 1990s, this study suggests that in the coming decades, the open North Atlantic will remain minimally affected by anthropogenic nitrogen deposition.
Drought losses in China might double between the 1.5 °C and 2.0 °C warming
Authors: Su Buda , Huang Jinlong , Fischer Thomas , Wang Yanjun , Kundzewicz Zbigniew W. , Zhai Jianqing , Sun Hemin , Wang Anqian , Zeng Xiaofan , Wang Guojie , Tao Hui , Gemmer Marco , Li Xiucang , Jiang Tong
Published: October 2018

Significance

We project drought losses in China under global warming of 1.5 °C and 2.0 °C. To assess future drought losses, we project the regional gross domestic product under shared socioeconomic pathways instead of using a static socioeconomic scenario. We identify increasing precipitation and evapotranspiration patterns. With increasing drought intensity and areal coverage across China, drought losses will increase considerably. The estimated losses in a sustainable development pathway at 1.5 °C warming will be 10 times higher than in the reference period 1986–2005 and three times higher than in 2006–2015. Yet, climate change mitigation, limiting the temperature increase to 1.5 °C, can considerably reduce the annual drought losses in China, compared with 2.0 °C warming.
Entropically driven aggregation of bacteria by host polymers promotes antibiotic tolerance in
Pseudomonas aeruginosa
Authors: Secor Patrick R. , Michaels Lia A. , Ratjen Anina , Jennings Laura K. , Singh Pradeep K.
Published: October 2018

Significance

Bacteria live in aggregates at sites of chronic infection, and aggregated growth is thought to be important in producing key infection phenotypes such as antibiotic tolerance. We found that entropic forces generated by polymers abundant at chronic infection sites can cause bacteria to aggregate by a mechanism known as “depletion aggregation.” This aggregation mechanism does not require biofilm formation functions, but it does cause bacteria to become much less susceptible to killing by antibiotics. These findings indicate that aggregation could be a default growth mode at infection sites. It might be useful to target mechanisms of depletion-mediated antibiotic tolerance for the treatment of chronic infections.
Early adolescent Rai1 reactivation reverses transcriptional and social interaction deficits in a mouse model of Smith–Magenis syndrome
Authors: Huang Wei-Hsiang , Wang David C. , Allen William E. , Klope Matthew , Hu Hailan , Shamloo Mehrdad , Luo Liqun
Published: October 2018

Significance

Losing one copy of the
RAI1
gene causes Smith–Magenis syndrome (SMS), a neurodevelopmental disorder. Using a newly generated SMS mouse model, this study demonstrates that restoring the
Rai1
gene dose in an early postnatal window could repair gene expression and social interaction deficits in this SMS model. The SMS mouse model also showed a reduced density of dendritic spines, anatomical correlates of excitatory synapses, in the prefrontal cortex. Artificial activation of prefrontal cortex neurons partially alleviated the behavioral deficits. These findings suggest that, similar to Rett syndrome, SMS is caused by disruption of a chromatin-modifying gene with reversible developmental phenotypes, highlighting the potential treatment windows in childhood or adolescence.
Functional muscle recovery with nanoparticle-directed M2 macrophage polarization in mice
Authors: Raimondo Theresa M. , Mooney David J.
Published: October 2018

Significance

Chronic inflammation contributes to the progression of many diseases, including 7 of the 10 leading causes of death. Macrophages play a central role in regulating inflammation because they adopt proinflammatory (M1) and proregenerative (M2) phenotypes. While an initial M1 response is critical, the prolonged presence of M1 macrophages, or the imbalance of M1 over M2 macrophages, can cause tissue damage and inhibit regeneration. We demonstrate that gold nanoparticles can be used to deliver a cytokine to direct M2 macrophage polarization following muscle injury in vivo. The polarization shift promoted regeneration and increased muscle strength. The ability to direct macrophage polarization in an inflammatory microenvironment may be useful in the treatment of many injuries and inflammatory diseases.
Space radiation triggers persistent stress response, increases senescent signaling, and decreases cell migration in mouse intestine
Authors: Kumar Santosh , Suman Shubhankar , Fornace Albert J. , Datta Kamal
Published: October 2018

Significance

Coordinated epithelial cell migration is key to maintaining functional integrity and preventing pathological processes in gastrointestinal tissue, and is essential for astronauts’ health and space mission success. Here we show that energetic heavy ions, which are more prevalent in deep space relative to low-Earth orbit, could persistently decrease intestinal epithelial cell migration, alter cytoskeletal remodeling, and increase cell proliferation with ongoing DNA damage and cell senescence, even a year after irradiation. Our study has provided the molecular underpinnings for energetic heavy-ion
56
Fe radiation-induced cell migration alterations, and raises a potentially serious concern, particularly for long-term deep-space manned missions.
Tradeoffs in environmental and equity gains from job accessibility
Authors: Stokes Eleanor C. , Seto Karen C.
Published: October 2018

Significance

Access to employment is key to the sustainability of urban areas. Although changes in access have consequences for multiple pillars of sustainability, in tandem, potential tradeoffs are rarely explored. This analysis measures employment accessibility trends over the past decade across and within US urban areas and assesses how these trends may be shaping emissions and social equity. We find that although US urban areas have increased in accessibility by 11% on average, few increases have provided both environmental and social value simultaneously. This study points to a paradox in sustainable development, where emissions mitigation and the welfare of low-income urban residents can be at odds.
Serotonin signaling regulates insulin-like peptides for growth, reproduction, and metabolism in the disease vector
Aedes aegypti
Authors: Ling Lin , Raikhel Alexander S.
Published: October 2018

Significance

Mosquitoes pose an enormous threat to humans by transmitting numerous dangerous diseases. To become reproductively competent and effective disease vectors, it is crucial for them to achieve optimal body size and nutritional status. Elucidation of these processes in mosquitoes has been hampered by the lack of classic genetics tools. CRISPR-Cas9 disruption of the fat-body–specific serotonin receptor
Aa5HT2B
impairs body growth and lipid accumulation in
Aedes aegypti
mosquitoes, the vectors of dengue fever, yellow fever, and Zika virus. Aa5HT2B controls insulin-like peptides. Using the CRISPR-Cas9 approach, we have uncovered differential roles of insulin-like peptides in the control of body size and metabolism, and provided a link between blood feeding and the fat-body–specific serotonin signaling.
Proinsulin C-peptide is an autoantigen in people with type 1 diabetes
Authors: So Michelle , Elso Colleen M. , Tresoldi Eleonora , Pakusch Miha , Pathiraja Vimukthi , Wentworth John M. , Harrison Leonard C. , Krishnamurthy Balasubramanian , Thomas Helen E. , Rodda Christine , Cameron Fergus J. , McMahon Jacinta , Kay Thomas W. H. , Mannering Stuart I.
Published: October 2018

Significance

Type 1 diabetes (T1D) is an incurable autoimmune disease caused by T cell-mediated destruction of insulin-producing beta cells. The beta-cell antigens recognized by human CD4
+
T cells in T1D are poorly defined. Here, we show that C-peptide, derived from proinsulin, is recognized by CD4
+
T cells from the blood of >60% of people with recent onset T1D. The majority of C-peptide–derived epitopes were recognized when presented by high-risk T1D HLA alleles. For some T cells, full-length C-peptide was a more potent stimulator than shorter peptides. Hence, our data suggests that full-length C-peptide may be uniquely antigenic in human T1D. C-peptide may be useful in assays to monitor changes in T cell autoimmunity and antigen-specific therapies for T1D.
Diplogastrellus
nematodes are sexually transmitted mutualists that alter the bacterial and fungal communities of their beetle host
Authors: Ledón-Rettig Cristina C. , Moczek Armin P. , Ragsdale Erik J.
Published: October 2018

A recent accumulation of studies has demonstrated that nongenetic, maternally transmitted factors are often critical to the health and development of offspring and can therefore play a role in ecological and evolutionary processes. In particular, microorganisms such as bacteria have been championed as heritable, symbiotic partners capable of conferring fitness benefits to their hosts. At the same time, parents may also pass various nonmicrobial organisms to their offspring, yet the roles of such organisms in shaping the developmental environment of their hosts remain largely unexplored. Here, we show that the nematode
Diplogastrellus monhysteroides
is transgenerationally inherited and sexually transmitted by the dung beetle
Onthophagus taurus
. By manipulating artificial chambers in which beetle offspring develop, we demonstrate that the presence of
D. monhysteroides
nematodes enhances the growth of beetle offspring, empirically challenging the paradigm that nematodes are merely commensal or even detrimental to their insect hosts. Finally, our research presents a compelling mechanism whereby the nematodes influence the health of beetle larvae:
D. monhysteroides
nematodes engineer the bacterial and fungal communities that also inhabit the beetle developmental chambers, including specific taxa known to be involved in biomass degradation, possibly allowing larval beetles better access to their otherwise recalcitrant, plant-based diet. Thus, our findings illustrate that nongenetic inheritance can include intermediately sized organisms that live and proliferate in close association with, and in certain cases enhance, the development of their hosts’ offspring.
High-throughput in vivo screen of functional mRNA delivery identifies nanoparticles for endothelial cell gene editing
Authors: Sago Cory D. , Lokugamage Melissa P. , Paunovska Kalina , Vanover Daryll A. , Monaco Christopher M. , Shah Nirav N. , Gamboa Castro Marielena , Anderson Shannon E. , Rudoltz Tobi G. , Lando Gwyneth N. , Munnilal Tiwari Pooja , Kirschman Jonathan L. , Willett Nick , Jang Young C. , Santangelo Philip J. , Bryksin Anton V. , Dahlman James E.
Published: October 2018

Significance

Nanoparticle-mediated delivery of siRNA to hepatocytes has treated disease in humans. However, systemically delivering RNA drugs to nonliver tissues remains an important challenge. To increase the number of nanoparticles that could be studied in vivo, we designed a high-throughput method to measure how >100 nanoparticles delivered mRNA that was translated into functional protein in vivo. We quantified how >250 lipid nanoparticles (LNPs) delivered mRNA in vivo, identifying two LNPs that deliver mRNA to endothelial cells. One of the LNPs codelivered Cas9 mRNA and single-guide RNA in vivo, leading to endothelial cell gene editing. This approach can identify nanoparticles that target new cells.
Bypassing a 8,5′-cyclo-2′-deoxyadenosine lesion by human DNA polymerase η at atomic resolution
Authors: Weng Peter J. , Gao Yang , Gregory Mark T. , Wang Pengcheng , Wang Yinsheng , Yang Wei
Published: October 2018

Oxidatively induced DNA lesions 8,5′-cyclopurine-2′-deoxynucleosides (cdPus) are prevalent and cytotoxic by impeding DNA replication and transcription. Both the 5′R- and 5′S-diastereomers of cdPu can be removed by nucleotide excision repair; however, the 5′S-cdPu is more resistant to repair than the 5′Rcounterpart. Here, we report the crystal structures of human polymerase (Pol) η bypassing 5′S-8,5′-cyclo-2′-deoxyadenosine (cdA) in insertion and the following two extension steps. The cdA-containing DNA structures vary in response to the protein environment. Supported by the “molecular splint” of Pol η, the structure of 5′S-cdA at 1.75-Å resolution reveals that the backbone is pinched toward the minor groove and the adenine base is tilted. In the templating position, the cdA takes up the extra space usually reserved for the thymine dimer, and dTTP is efficiently incorporated by Pol η in the presence of Mn2+. Rigid distortions of the DNA duplex by cdA, however, prevent normal base pairing and hinder immediate primer extension by Pol η. Our results provide structural insights into the strong replication blockage effect and the mutagenic property of the cdPu lesions in cells.
Lesion network localization of free will
Authors: Darby R. Ryan , Joutsa Juho , Burke Matthew J. , Fox Michael D.
Published: October 2018

Significance

Free will consists of a desire to act (volition) and a sense of responsibility for that action (agency), but the brain regions responsible for these processes remain unknown. We found that brain lesions that disrupt volition occur in many different locations, but fall within a single brain network, defined by connectivity to the anterior cingulate. Lesions that disrupt agency also occur in many different locations, but fall within a separate network, defined by connectivity to the precuneus. Together, these networks may underlie our perception of free will, with implications for neuropsychiatric diseases in which these processes are impaired.
Many roads lead to Rome, and we have found seven
Authors: Christidou Sophia
Published: October 2018

Through our academic research we developed a control mechanism for translation based on seven variables derived from the studies of the Belgian translatologist Dirk Delabastita. In this paper we implement the control mechanism for translation in the fields of solid waste management and liquid waste mechanics using the academic text-books Handbook of Solid Waste Management and Wastewater Engineering, Treatment and Reuse in order to investigate the quality of translations in Greek. We present an indicative psychometric questionnaire from the initial research conducted with telecommunications scientists, as well as an abstract outlining the processing of the relevant indices, followed by indicative processing in the academic field of environmental engineering. This could be the first step in research for the field of environmental engineering terminology.
Structural insight into microtubule stabilization and kinesin inhibition by Tau family MAPs
Authors: Shigematsu Hideki , Imasaki Tsuyoshi , Doki Chihiro , Sumi Takuya , Aoki Mari , Uchikubo-Kamo Tomomi , Sakamoto Ayako , Tokuraku Kiyotaka , Shirouzu Mikako , Nitta Ryo
Published: October 2018

The Tau family microtubule-associated proteins (MAPs) promote microtubule stabilization and regulate microtubule-based motility. They share the C-terminal microtubule-binding domain, which includes three to five tubulin-binding repeats. Different numbers of repeats formed by alternative splicing have distinct effects on the activities of these proteins, and the distribution of these variants regulates fundamental physiological phenomena in cells. In this study, using cryo-EM, we visualized the MAP4 microtubule complex with the molecular motor kinesin-1. MAP4 bound to the C-terminal domains of tubulins along the protofilaments stabilizes the longitudinal contacts of the microtubule. The strongest bond of MAP4 was found around the intertubulin–dimer interface such that MAP4 coexists on the microtubule with kinesin-1 bound to the intratubulin–dimer interface as well. MAP4, consisting of five repeats, further folds and accumulates above the intertubulin–dimer interface, interfering with kinesin-1 movement. Therefore, these cryo-EM studies reveal new insight into the structural basis of microtubule stabilization and inhibition of kinesin motility by the Tau family MAPs.
Legionella remodels the plasma membrane–derived vacuole by utilizing exocyst components as tethers
Authors: Arasaki Kohei , Kimura Hana , Tagaya Mitsuo , Roy Craig R.
Published: October 2018

During the initial stage of infection, Legionella pneumophila secretes effectors that promote the fusion of endoplasmic reticulum (ER)–derived vesicles with the Legionella-containing vacuole (LCV). This fusion leads to a remodeling of the plasma membrane (PM)–derived LCV into a specialized ER-like compartment that supports bacterial replication. Although the effector DrrA has been shown to activate the small GTPase Rab1, it remains unclear how DrrA promotes the tethering of host vesicles with the LCV. Here, we show that Sec5, Sec15, and perhaps Sec6, which are subunits of the exocyst that functions in the tethering of exocytic vesicles with the PM, are required for DrrA-mediated, ER-derived vesicle recruitment to the PM-derived LCV. These exocyst components were found to interact specifically with a complex containing DrrA, and the loss of Sec5 or Sec15 significantly suppressed the recruitment of ER-derived vesicles to the LCV and inhibited intracellular replication of Legionella. Importantly, Sec15 is recruited to the LCV, and Rab1 activation is necessary for this recruitment.
Bidirectional intraflagellar transport is restricted to two sets of microtubule doublets in the trypanosome flagellum
Authors: Bertiaux Eloïse , Mallet Adeline , Fort Cécile , Blisnick Thierry , Bonnefoy Serge , Jung Jamin , Lemos Moara , Marco Sergio , Vaughan Sue , Trépout Sylvain , Tinevez Jean-Yves , Bastin Philippe
Published: October 2018

Intraflagellar transport (IFT) is the rapid bidirectional movement of large protein complexes driven by kinesin and dynein motors along microtubule doublets of cilia and flagella. In this study, we used a combination of high-resolution electron and light microscopy to investigate how and where these IFT trains move within the flagellum of the protist Trypanosoma brucei. Focused ion beam scanning electron microscopy (FIB-SEM) analysis of trypanosomes showed that trains are found almost exclusively along two sets of doublets (3–4 and 7–8) and distribute in two categories according to their length. High-resolution live imaging of cells expressing mNeonGreen::IFT81 or GFP::IFT52 revealed for the first time IFT trafficking on two parallel lines within the flagellum. Anterograde and retrograde IFT occurs on each of these lines. At the distal end, a large individual anterograde IFT train is converted in several smaller retrograde trains in the space of 3–4 s while remaining on the same side of the axoneme.
Excitable RhoA dynamics drive pulsed contractions in the early C. elegans embryo
Authors: Michaux Jonathan B. , Robin François B. , McFadden William M. , Munro Edwin M.
Published: October 2018

Pulsed actomyosin contractility underlies diverse modes of tissue morphogenesis, but the underlying mechanisms remain poorly understood. Here, we combined quantitative imaging with genetic perturbations to identify a core mechanism for pulsed contractility in early Caenorhabditis elegans embryos. We show that pulsed accumulation of actomyosin is governed by local control of assembly and disassembly downstream of RhoA. Pulsed activation and inactivation of RhoA precede, respectively, the accumulation and disappearance of actomyosin and persist in the absence of Myosin II. We find that fast (likely indirect) autoactivation of RhoA drives pulse initiation, while delayed, F-actin–dependent accumulation of the RhoA GTPase-activating proteins RGA-3/4 provides negative feedback to terminate each pulse. A mathematical model, constrained by our data, suggests that this combination of feedbacks is tuned to generate locally excitable RhoA dynamics. We propose that excitable RhoA dynamics are a common driver for pulsed contractility that can be tuned or coupled differently to actomyosin dynamics to produce a diversity of morphogenetic outcomes.
Revisiting Copyright Theories: Democratic Culture and the Resale of Digital Goods
Authors: Sang Yoonmo
Published: October 2018

This study surveys theoretical justifications for copyright and considers the implications of the notion of cultural democracy in regard to copyright law and policy. In doing so, the study focuses on the first sale doctrine and advocates for the doctrine’s expansion to digital goods based on a discussion of the doctrine’s policy implications and a review of the arguments for and against a digital first sale doctrine. The study argues that democratic copyright theories, in general, and the notion of cultural democracy, in particular, can and should guide copyright reforms in conjunction with a digital first sale doctrine. This study contributes to the growing discussions about the democratic theories of copyright by demonstrating their applicability to copyright policy and doctrine.
Effects of Acute Exercise Combined With Calorie Restriction Initiated Late-in-Life on Insulin Signaling, Lipids, and Glucose Uptake in Skeletal Muscle From Old Rats
Authors: Oki Kentaro , Arias Edward B , Kanzaki Makoto , Cartee Gregory D
Published: October 2018

We evaluated effects of calorie restriction (CR: consuming 60–65% of ad libitum [AL] intake) initiated late-in-life with or without acute exercise on insulin-stimulated glucose uptake (ISGU) of skeletal muscle by studying four groups of 26-month-old rats: sedentary-AL, sedentary-CR (8-week duration), 3 hours post-exercise (3hPEX)-AL and 3hPEX-CR. ISGU was determined in isolated epitrochlearis muscles incubated ± insulin. Muscles were assessed for signaling proteins (immunoblotting) and lipids (mass spectrometry). ISGU from sedentary-CR and 3hPEX-AL exceeded sedentary-AL; 3hPEX-CR exceeded all other groups. Akt (Ser473, Thr308) and Akt substrate of 160 kDa (AS160; Ser588, Thr642, Ser704) phosphorylation levels tracked with ISGU. Among the 477 lipids detected, 114 were altered by CR (including reductions in 15 of 25 acylcarnitines), and 27 were altered by exercise (including reductions in 18 of 22 lysophosphatidylcholines) with only six lipids overlapping between CR and exercise. ISGU significantly correlated with 23 lipids, including: acylcarnitine 20:1 (r = .683), lysophosphatidylethanolamine19:0 (r = −.662), acylcarnitine 24:0 (r = .611), and plasmenyl-phosphatidylethanolamine 37:5 (r = −.603). Muscle levels of ceramides (a lipid class previously linked to insulin resistance) were not altered by CR and/or exercise nor significantly correlated with ISGU, implicating other mechanisms (which potentially involve other lipids identified in this study) for greater ISGU and Akt and AS160 phosphorylation with these interventions.
Daily Links Between Sleep and Anger Among Spouses of Chronic Pain Patients
Authors: Marini Christina M , Martire Lynn M , Jones Dusti R , Zhaoyang Ruixue , Buxton Orfeu M
Published: October 2018

Objectives

This study identified daily associations between sleep, emotion, and marital functioning in the context of chronic pain. Because spouses’ sleep is compromised on nights when patients experience more pain, we set out to identify implications of spouses’ sleep for their own emotion (anger) upon waking and marital interaction (marital tension) throughout the rest of the day. We further considered whether spouses’ critical attitudes about patients’ pain-related coping exacerbated associations between their sleep, morning anger, and marital tension.

Method

Data came from a study of knee osteoarthritis patients (50+ years old) and spouses (N = 138 couples) who completed daily diaries across 22 days. Multilevel models were estimated to test hypotheses.

Results

Spouses woke up angrier on mornings when they reported that their sleep was more unrefreshing than usual. This association was stronger among more critical spouses. Morning anger resulting from unrefreshing sleep, however, did not predict marital tension throughout the rest of the day.

Discussion

Findings highlight the potential value of intervention efforts aimed at promoting spouses’ sleep quality in an effort to offset negative emotional consequences that may undermine spouses’ and patients’ adjustment in the context of chronic pain.
Radiological Characteristics and Natural History of Adult IDH-Wildtype Astrocytomas with TERT Promoter Mutations
Authors: Izquierdo Cristina , Barritault Marc , Poncet Delphine , Cartalat Stéphanie , Joubert Bastien , Bruna Jordi , Jouanneau Emmanuel , Guyotat Jacques , Vasiljevic Alexandre , Fenouil Tanguy , Berthezène Yves , Honnorat Jérôme , Meyronet David , Ducray François
Published: October 2018

BACKGROUND

Adult IDH-wildtype astrocytomas with TERT promoter mutations (TERTp) are associated with a poor prognosis.

OBJECTIVE

To analyze the radiological presentation and natural history of adult IDH-wildtype astrocytomas with TERTp.

METHODS

We retrospectively reviewed the characteristics of 40 IDH-wildtype TERTp-mutant astrocytomas (grade II n = 19, grade III n = 21) and compared them to those of 114 IDH-mutant lower grade gliomas (LGG), of 92 IDH-wildtype TERTp-mutant glioblastomas, and of 15 IDH-wildtype TERTp-wildtype astrocytomas.

RESULTS

Most cases of IDH-wildtype TERTp-mutant astrocytomas occurred in patients aged >50 yr (88%) and presented as infiltrative lesions without contrast enhancement (73%) that were localized in the temporal and/or insular lobes (37.5%) or corresponded to a gliomatosis cerebri (43%). Thalamic involvement (33%) and extension to the brainstem (27%) were frequently observed, as was gyriform infiltration (33%). This radiological presentation was different from that of IDH-mutant LGG, IDH-wildtype TERTp-mutant glioblastomas, and IDH-wildtype TERTp-wildtype astrocytomas. Tumor evolution before treatment initiation was assessable in 17 cases. Ten cases demonstrated a rapid growth characterized by the apparition of a ring-like contrast enhancement and/or a median velocity of diametric expansion (VDE) ≥8 mm/yr but 7 cases displayed a slow growth (VDE <8 mm/yr) that could last several years before anaplastic transformation. Median overall survival of IDH-wildtype TERTp-mutant astrocytomas was 27 mo.

CONCLUSION

IDH-wildtype TERTp-mutant astrocytomas typically present as nonenhancing temporo-insular infiltrative lesions or as gliomatosis cerebri in patients aged >50 yr. In the absence of treatment, although rapid tumor growth is frequent, an initial falsely reassuring, slow growth can be observed.
The Effect of Ultra–low-dose Intrathecal Naloxone on Pain Intensity After Lumbar Laminectomy With Spinal Fusion: A Randomized Controlled Trial
Authors: Firouzian Abolfazl , Gholipour Baradari Afshin , Ehteshami Saeid , Zamani Kiasari Alieh , Shafizad Misagh , Shafiei Sajad , Younesi Rostami Fatemeh , Alipour Abbas , Ala Shahram , Darvishi-Khezri Hadi , Haddadi Kaveh
Published: October 2018

Background:

Despite advances in pain management, several patients continue to experience severe acute pain after lumbar spine surgery. The aim of this study was to assess the safety and effectiveness of single ultra–low-dose intrathecal (IT) naloxone in combination with IT morphine for reducing pain intensity, pruritus, nausea, and vomiting in patients undergoing lumbar laminectomy with spinal fusion.

Materials and Methods:

In this double-blind trial, patients scheduled for lumbar laminectomy with spinal fusion were randomly assigned to receive single ultra–low-dose IT naloxone (20 μg) and IT morphine (0.2 mg) (group M+N) or IT morphine (0.2 mg) alone (group M). The severity of postoperative pain, pruritus and nausea, and frequency of vomiting were assessed at recovery from anesthesia and, subsequently, at 1, 3, 6, 12, and 24 hours postoperatively using an 11-point (0-10) visual analogue scale.

Results:

A total of 77 patients completed the study, and there were significant differences in postoperative pain, pruritus, and nausea visual analogue scale between the groups (P<0.05). After adjusting for body mass index and surgery duration, IT naloxone administration reduced the pain score (coefficient=1.84; 95% confidence interval [CI], 1.05-2.63; P<0.001), and the scores of pruritus and nausea (coefficient=0.9; 95% CI, 0.44-1.37; P<0.001 and coefficient=0.71; 95% CI, 0.12-1.31; P=0.02, respectively) compared with IT morphine alone. No serious adverse effects were observed.

Conclusions:

The addition of ultra–low-dose IT naloxone to IT morphine provides excellent postoperative pain management and effectively controls pruritus and nausea in patients undergoing laminectomy with spinal fusion.
Uterine Tumor Resembling Ovarian Sex Cord Tumor
Authors: Dickson Brendan C. , Childs Timothy J. , Colgan Terrence J. , Sung Yun-Shao , Swanson David , Zhang Lei , Antonescu Cristina R.
Published: October 2018

Uterine tumor resembling ovarian sex-cord tumor (UTROSCT) is a rare and distinctive neoplasm of unclear histogenesis, and uncertain malignant potential. These neoplasms morphologically resemble sex-cord stromal tumors of the ovary, and possess a polyphenotypic immunophenotype. Their molecular pathogenesis has yet to be elucidated; notably, however, tumors lack alterations found in other uterine tumors bearing sex-cord–like differentiation, such as endometrial stromal sarcoma. Following identification of an index patient with anESR1-NCOA3fusion gene by RNA-sequencing, we undertook a retrospective review for additional cases of UTROSCT. We identified a total of 4 patients, with an average age of 53 years (range, 38 to 68 y). RNA-sequencing was performed in all cases, revealing anESR1-NCOA3fusion in 2 cases and one case each with relatedESR1-NCOA2andGREB1-NCOA2fusions. Each of the tumors showed histologic and an immunophenotype features within the previously reported spectrum of UTROSCT; interestingly, one case contained prominent spindle cell fascicles and another was largely comprised of sheets of small round cells. Our results demonstrate UTROSCT are defined by recurrent fusions involvingNCOA2orNCOA3, a finding that is directly amenable to diagnostic evaluation. This study confirms UTROSCT is molecularly distinct from endometrial stromal sarcoma, and raises intriguing new questions into the pathogenesis of these neoplasms and possible relationship with otherNCOAfusion-positive uterine tumors.
Heterogeneity of Fibrosis in Liver Biopsies of Patients With Heart Failure Undergoing Heart Transplant Evaluation
Authors: Dhall Deepti , Kim Stacey A. , Mc Phaul Christopher , Kransdorf Evan P. , Kobashigawa Jon A. , Sundaram Vinay , Mirocha James , Guindi Maha
Published: October 2018

Liver biopsies are commonly performed in heart transplant candidates to confirm congestive hepatopathy (CH) and to assess the degree of fibrosis. Heterogeneity of fibrosis is frequent in CH, making it difficult to stage fibrosis. In this study, we evaluated the prevalence of heterogeneity of fibrosis and nodular regenerative hyperplasia (NRH) in liver biopsies with CH secondary to heart failure. Fifty liver biopsies with CH secondary to heart failure were reviewed. The fibrosis was scored on trichrome stain as follows: stage 0 for no fibrosis, stage 1 for zone 3 fibrosis, stage 2 for zone 3 and portal fibrosis, stage 3 for bridging fibrosis, and stage 4 for cirrhosis. Both stage 3 and stage 4 fibrosis were classified as advanced fibrosis. A predominant pattern of fibrosis and a secondary pattern of fibrosis, defined as a different stage of fibrosis seen in at least 10% of the biopsy material, if present, were recorded. A biopsy was considered to show heterogenous fibrosis if there was at least a 2 stage difference between the predominant and secondary patterns. Thirteen biopsies (26%) showed heterogenous fibrosis. Sixteen biopsies (32%) showed some evidence of advanced fibrosis: 5 had uniform advanced fibrosis, 4 had predominant pattern of advanced fibrosis, and advanced fibrosis was focal in 7 biopsies from 6 patients. NRH-type changes were seen in 9 of 50 biopsies (18%). In conclusion, our study showed heterogenous fibrosis in the liver biopsy of a quarter of patients with CH due to heart failure, highlighting the limitations of fibrosis assessment in the biopsies, and suggests that correlation with the complete clinical information is essential for management decisions.