bluuebunny/crossref_metadata_2025 huggingface dataset:
Palliative care health professionals’ experiences of caring for patients with advance care directives
Authors: Johnson Claire E. , Singer Rachel , Masso Malcolm , Sellars Marcus , Silvester William
Published: January 2015

Objective
To explore the health professionals’ (HPs) perceptions and experiences of advance care directives (ACDs) and advance care planning in Australian palliative care services.

Methods
A nationwide survey of 105 palliative care services was conducted, with two HPs from each service invited to participate. A qualitative analysis of open responses about advance care planning was undertaken.

Results
Sixty questionnaires were returned with open responses. Most responders were nurses (75%), aged ≥40 years (80%) and with a mean of 12 years palliative care experience. Data were grouped into four key themes: (1) the ACD; (2) the process of developing ACDs; (3) the process of using ACDs; and (4) the consequences of having ACDs. Participants were positive about advance care planning, commenting that ongoing communication about end-of-life care ensures mutual understanding between patients, family and HPs. Provision of care was considered easier and more efficient with an ACD in place. ACDs were perceived to reduce distrust and conflict between family, friends and HPs, and promote communication. Suboptimal documentation, clarity and explicitness limited the usefulness of ACDs when they were available.

Conclusions
Advance care planning benefits HPs, patients and their family. To maximise these benefits, ACDs need to be clear, comprehensive, medically relevant and transportable documents.

What is known about the topic?
Ideally, advance care planning encompasses the identification and documentation of a person’s preferences for future medical treatments and care in preparation for an occasion when the person cannot express their values and wishes. The uptake and practice of advance care planning is inconsistent, and the extent to which it is used by health professionals and patients is variable. Many people are cared for at the end of life in specialist palliative care services, but the intersection between palliative care and advance care planning remains under-researched.

What does this paper adds?
ACDs facilitate communication and advance care planning; help establish trust between health professionals, patients and their families; and make multiple aspects of care easier for HPs. Processes surrounding ACDs, particularly inadequate documentation, limit adherence and application.

What are the implications for practitioners?
Clear communication is necessary for effective ACD development and application. The presence of an ACD makes communication and advance care planning easier, and improves trust between HPs, patients and their family. To be useful, ACDs must be clear, comprehensive, medically relevant, transportable documents.
Locally adaptive, spatially explicit projection of US population for 2030 and 2050
Authors: McKee Jacob J. , Rose Amy N. , Bright Edward A. , Huynh Timmy , Bhaduri Budhendra L.
Published: January 2015

Significance

Oak Ridge National Laboratory (ORNL) is a leader in population distribution and dynamics research, particularly in developing gridded population datasets. For this study, ORNL researchers leverage their expertise in intelligent dasymetric modeling to construct large-scale, national level, spatially distributed population projections for the contiguous United States. The model presented here departs from other spatially explicit projection models by accounting for socioeconomic and cultural characteristics that influence spatial population growth at smaller scales, while still projecting population at a large scale. The resulting projected population distribution can be exploited for long-term urban and infrastructure planning, and scientific modeling for climate change.
Fatty acid synthase is preferentially degraded by autophagy upon nitrogen starvation in yeast
Authors: Shpilka Tomer , Welter Evelyn , Borovsky Noam , Amar Nira , Shimron Frida , Peleg Yoav , Elazar Zvulun
Published: January 2015

Significance

Starvation-induced protein degradation by autophagy is considered to be nonselective. This study provides evidence, however, that upon nitrogen starvation fatty acid synthase is selectively degraded by autophagy. Our results suggest that fatty acid synthase degradation by the autophagic pathway is essential to maintain cell homeostasis under starvation.
Dynamics of a morbillivirus at the domestic–wildlife interface: Canine distemper virus in domestic dogs and lions
Authors: Viana Mafalda , Cleaveland Sarah , Matthiopoulos Jason , Halliday Jo , Packer Craig , Craft Meggan E. , Hampson Katie , Czupryna Anna , Dobson Andrew P. , Dubovi Edward J. , Ernest Eblate , Fyumagwa Robert , Hoare Richard , Hopcraft J. Grant C. , Horton Daniel L. , Kaare Magai T. , Kanellos Theo , Lankester Felix , Mentzel Christine , Mlengeya Titus , Mzimbiri Imam , Takahashi Emi , Willett Brian , Haydon Daniel T. , Lembo Tiziana
Published: January 2015

Significance

Morbilliviruses are a growing concern because of their ability to infect multiple species. The spill-over of canine distemper virus (CDV) from domestic dogs has been associated with severe declines in wild carnivores worldwide, and therefore mass dog vaccination has been suggested as a potential control strategy. Focusing on three decades of CDV exposure data in dogs and lions of the Serengeti, we show that cyclic infection dynamics in lions initially driven by dogs became more frequent and asynchronous, suggesting that the wider dog population and other wildlife species drive CDV dynamics. Hence, although widespread dog vaccination reduced the infection in dogs, transmission to lion populations still occurred, warranting further investigation into effective management options of CDV in this species-rich ecosystem.
Short time interval for condensation of high-temperature silicates in the solar accretion disk
Authors: Luu Tu-Han , Young Edward D. , Gounelle Matthieu , Chaussidon Marc
Published: January 2015

Significance

Combining bulk and in situ Mg isotope measurements allows dating the formation of chondrule precursors relative to that of chondrules themselves. This has never been achieved before and has profound implications for the origin of chondrules, the origin of their precursors, and the evolution of the solar protoplanetary disk. There is a minimum bulk chondrule isochron, analogous in some ways to the bulk calcium−aluminum-rich inclusion isochron, which dates either the cessation of condensation of chondrule precursors or the cessation of their transport to the regions where chondrules formed.
Autocrine regulation of ecdysone synthesis by β3-octopamine receptor in the prothoracic gland is essential for
Drosophila
metamorphosis
Authors: Ohhara Yuya , Shimada-Niwa Yuko , Niwa Ryusuke , Kayashima Yasunari , Hayashi Yoshiki , Akagi Kazutaka , Ueda Hitoshi , Yamakawa-Kobayashi Kimiko , Kobayashi Satoru
Published: January 2015

Significance

Metamorphosis is an important biological process by which animals alter their body structures to become sexually mature adults. We discovered that tyramine signaling through the β3-octopamine receptor plays an essential role in producing the steroid hormone ecdysone, which is critical for metamorphosis. Based on our observations, we propose that monoamine signaling acts downstream of a body size checkpoint that allows metamorphosis to occur only when a critical body weight is attained during larval development and nutrients are sufficiently abundant. This work also provides a new perspective on an evolutionarily conserved monoaminergic regulation of steroid hormone production during developmental transitions such as metamorphosis. This study provides a new understanding of how metamorphosis is coordinately regulated by nutritional conditions and developmental timing.
Abrupt tectonics and rapid slab detachment with grain damage
Authors: Bercovici David , Schubert Gerald , Ricard Yanick
Published: January 2015

Significance

Subduction zones are delineated by Earth’s ocean trenches, and are where tectonic plates sink into the mantle as cold heavy slabs, which in turn drive plate motion. But slabs can detach from their surface plates, thus altering tectonic driving forces. Slab detachment can occur if thick crust from continents or oceanic plateaux is swept by plate motion into the subduction zone, thus plugging it up. Detachment is also accelerated because mineral grains in the slab become smaller during deformation, causing the slab to weaken rapidly while being stretched. The combination of crustal plugs with weakening causes abrupt slab detachment in a few million years, which can account for observed precipitous changes in plate tectonic motion and rapid continental uplift.
X-ray crystallographic and EPR spectroscopic analysis of HydG, a maturase in [FeFe]-hydrogenase H-cluster assembly
Authors: Dinis Pedro , Suess Daniel L. M. , Fox Stephen J. , Harmer Jenny E. , Driesener Rebecca C. , De La Paz Liliana , Swartz James R. , Essex Jonathan W. , Britt R. David , Roach Peter L.
Published: January 2015

Significance

Hydrogenases are a source of environmentally benign bioenergy, catalyzing the reversible reduction of protons to form hydrogen. The most active subclass, the [FeFe]-hydrogenases, is dependent on a metallocofactor, the H cluster, which contains iron-bound CO and CN
−
ligands. Although the HydG maturase is known to catalytically form a CO- and CN
−
-bound iron precursor to the H cluster, mechanistic insight into this complex process has been hampered by the lack of structural information about HydG. We now describe the high-resolution crystal structure and EPR analysis of HydG. These results reveal a previously unreported [5Fe-5S] cluster that features a labile iron center proposed to provide the site of formation for a labile Fe(CO)
2
CN synthon, the precursor of the diiron subcluster hydrogenase H cluster.
Low spatial coherence electrically pumped semiconductor laser for speckle-free full-field imaging
Authors: Redding Brandon , Cerjan Alexander , Huang Xue , Lee Minjoo Larry , Stone A. Douglas , Choma Michael A. , Cao Hui
Published: January 2015

Significance

There has been an intense search for the ideal light sources for high-speed, full-field imaging applications ranging from next-generation microscopes and laser projectors to digital holography and photolithography. Traditional lasers, although providing the required brightness (i.e., power per mode), exhibit high spatial coherence, which introduces coherent artifacts such as speckle, corrupting image formation. At the other extreme, low spatial coherence sources such as thermal sources and light emitting diodes (LEDs) avoid speckle but lack sufficient power per mode for high-speed imaging. In this work, we demonstrate a new type of semiconductor laser based on a chaotic cavity, which combines low spatial coherence with high power per mode. Such a laser could enable a wide range of full-field imaging applications.
Higd1a
is a positive regulator of cytochrome
c
oxidase
Authors: Hayashi Takaharu , Asano Yoshihiro , Shintani Yasunori , Aoyama Hiroshi , Kioka Hidetaka , Tsukamoto Osamu , Hikita Masahide , Shinzawa-Itoh Kyoko , Takafuji Kazuaki , Higo Shuichiro , Kato Hisakazu , Yamazaki Satoru , Matsuoka Ken , Nakano Atsushi , Asanuma Hiroshi , Asakura Masanori , Minamino Tetsuo , Goto Yu-ichi , Ogura Takashi , Kitakaze Masafumi , Komuro Issei , Sakata Yasushi , Tsukihara Tomitake , Yoshikawa Shinya , Takashima Seiji
Published: January 2015

Significance

We identified hypoxia-inducible domain family, member 1A (Higd1a) as a positive regulator of cytochrome
c
oxidase (CcO). CcO, the terminal component of the mitochondrial electron transfer system, reductively converts molecular oxygen to water coupled to pump protons across the inner mitochondrial membrane. Higd1a is transiently induced under hypoxic conditions and increases CcO activity by directly interacting with CcO in the vicinity of its active center. Induction of Higd1a leads to increased oxygen consumption and subsequent mitochondrial ATP synthesis, thereby improving cell viability under hypoxia.
Neuronal UCP1 expression suggests a mechanism for local thermogenesis during hibernation
Authors: Laursen Willem J. , Mastrotto Marco , Pesta Dominik , Funk Owen H. , Goodman Jena B. , Merriman Dana K. , Ingolia Nicholas , Shulman Gerald I. , Bagriantsev Sviatoslav N. , Gracheva Elena O.
Published: January 2015

Significance

Mammalian hibernators can reduce their metabolic rate by 95% and body temperature to 2 °C. However, their central and peripheral nervous systems retain activity even in cold, through unknown mechanisms. We report here that neurons from hibernating squirrels express uncoupling protein 1 (UCP1), a protein known as a heat generator in brown adipose tissue. We show that squirrel UCP1 acts as the typical thermogenic protein and is up-regulated during torpor, suggesting its thermogenic capability is important during hibernation. Accordingly, we found that the temperature of squirrel brain during the deep torpor associated with hibernation is warmer than the surrounding tissues. We hypothesize that neuronal UCP1 allows squirrels to withstand the long hibernation season and tolerate temperatures prohibitively low for survival and neuronal function in nonhibernating species.
Specialized insulin is used for chemical warfare by fish-hunting cone snails
Authors: Safavi-Hemami Helena , Gajewiak Joanna , Karanth Santhosh , Robinson Samuel D. , Ueberheide Beatrix , Douglass Adam D. , Schlegel Amnon , Imperial Julita S. , Watkins Maren , Bandyopadhyay Pradip K. , Yandell Mark , Li Qing , Purcell Anthony W. , Norton Raymond S. , Ellgaard Lars , Olivera Baldomero M.
Published: January 2015

Significance

The discovery and characterization of insulin, a key hormone of energy metabolism, provided a life-saving drug for diabetics. We show that insulin can be subverted for nefarious biological purposes: Venomous cone snails use specialized insulins to elicit hypoglycemic shock, facilitating capture of their fish prey. This finding extends our understanding of the chemical and functional diversity of venom components, such that the snail’s arsenal includes a diverse set of neurotoxins that alters neuronal circuitry, as well as components that override glucose homeostasis. The highly expressed venom insulins are distinct from molluscan insulins and exhibit remarkable similarity to fish insulins. They are the smallest of all insulins characterized from any source, potentially providing new insights into structure-function elements of insulin action.
Improved tumor vascularization after anti-VEGF therapy with carboplatin and nab-paclitaxel associates with survival in lung cancer
Authors: Heist Rebecca S. , Duda Dan G. , Sahani Dushyant V. , Ancukiewicz Marek , Fidias Panos , Sequist Lecia V. , Temel Jennifer S. , Shaw Alice T. , Pennell Nathan A. , Neal Joel W. , Gandhi Leena , Lynch Thomas J. , Engelman Jeffrey A. , Jain Rakesh K.
Published: January 2015

Significance

A better mechanistic understanding of the survival benefits and identification of biomarkers of response would greatly enhance the optimal utilization of antiangiogenic agents such as bevacizumab in combination with chemotherapy in the treatment of cancer. This study indicates that the benefits of bevacizumab with chemotherapy in non–small cell lung cancer (NSCLC) patients may depend on tumor vascular function during treatment. These correlative studies also provide new insights into the selection of NSCLC patients most likely to benefit from the addition of bevacizumab treatment to chemotherapy. The imaging and circulating biomarker candidates should be further evaluated in larger studies.
A comparison of worldwide phonemic and genetic variation in human populations
Authors: Creanza Nicole , Ruhlen Merritt , Pemberton Trevor J. , Rosenberg Noah A. , Feldman Marcus W. , Ramachandran Sohini
Published: January 2015

Significance

Linguistic data are often combined with genetic data to frame inferences about human population history. However, little is known about whether human demographic history generates patterns in linguistic data that are similar to those found in genetic data at a global scale. Here, we analyze the largest available datasets of both phonemes and genotyped populations. Similar axes of human geographic differentiation can be inferred from genetic data and phoneme inventories; however, geographic isolation does not necessarily lead to the loss of phonemes. Our results show that migration within geographic regions shapes phoneme evolution, although human expansion out of Africa has not left a strong signature on phonemes.
Enhancer-bound LDB1 regulates a corticotrope promoter-pausing repression program
Authors: Zhang Feng , Tanasa Bogdan , Merkurjev Daria , Lin Chijen , Song Xiaoyuan , Li Wenbo , Tan Yuliang , Liu Zhijie , Zhang Jie , Ohgi Kenneth A. , Krones Anna , Skowronska-Krawczyk Dorota , Rosenfeld Michael G.
Published: January 2015

Significance

The apparent importance of promoter:enhancer looping is well established; however, the molecular mechanisms of these interactions in gene activation vs. gene repression remain to be fully elucidated. Here, we report that LIM domain-binding protein 1 (LDB1) can function in transcriptional enhancer-mediated gene activation mainly at the level of transcription initiation by regulating promoter:enhancer looping, consequent to the recruitment to basic helix-loop-helix–bound enhancers in pituitary corticotrope cells. Intriguingly, LDB1 also mediates promoter:enhancer looping required for target gene repression, acting at the level of promoter pausing, by recruiting metastasis-associated 1 family, member 2 to these repressive enhancers. These findings shed light on a regulatory aspect of the molecular function of LDB1, providing a putative mechanism of enhancer-dependent transcriptional repression.
Kinetics of protein–ligand unbinding: Predicting pathways, rates, and rate-limiting steps
Authors: Tiwary Pratyush , Limongelli Vittorio , Salvalaglio Matteo , Parrinello Michele
Published: January 2015

Significance

A crucial factor for drug efficacy is not just the binding affinity, but also the mean residence time in the binding pocket, usually quantified by its inverse,
k

off

. This is an important parameter that regulates the time during which the drug is active. Whereas the calculation of the binding affinity is by now routine, the calculation of
k

off

has proven more challenging because the timescales involved far exceed the limits of standard molecular dynamics simulation. We propose a metadynamics-based strategy that allows reaching timescales of seconds, and estimate
k

off

along with unbinding pathways and associated dynamical bottlenecks. The protocol is exemplified for trypsin–benzamidine unbinding. This work is a step towards a more effective computer-based drug design.
Clonal analysis reveals a common origin between nonsomite-derived neck muscles and heart myocardium
Authors: Lescroart Fabienne , Hamou Wissam , Francou Alexandre , Théveniau-Ruissy Magali , Kelly Robert G. , Buckingham Margaret
Published: January 2015

Significance

Head muscles, derived from the first and second pharyngeal arches, share common progenitors with myocardial cells of the heart. This is in contrast to somite-derived skeletal muscles of the trunk and limbs. Neck muscles, located in the transition zone between head and trunk, have both a somitic and nonsomitic origin. We now demonstrate a clonal relationship between nonsomitic neck muscles and myocardial cells located in the atria, inflow and outflow regions of the heart. This is distinct from that of the two head muscle lineages. Formation of these neck muscles, like those in the head, depends on a gene regulatory network shared with myocardial progenitors. We thus identify a third clonal group within cardiopharyngeal mesoderm, with implications for human malformations.
MITF drives endolysosomal biogenesis and potentiates Wnt signaling in melanoma cells
Authors: Ploper Diego , Taelman Vincent F. , Robert Lidia , Perez Brian S. , Titz Björn , Chen Hsiao-Wang , Graeber Thomas G. , von Euw Erika , Ribas Antoni , De Robertis Edward M.
Published: January 2015

Significance

MITF, a master regulator of melanocytes and a major melanoma oncogene amplified in 30-40% of melanomas, determines proliferative or invasive phenotypes. Previously unrecognized as a driver of lysosomal biogenesis, we found that
MITF
expression correlates with many lysosomal genes and generates late endosomes that are not functional in proteolysis. This accumulation of incomplete organelles expands the late endosomal compartment, enhancing Wnt signaling by entrapping the Wnt machinery in multivesicular bodies. Wnt signaling can stabilize many proteins besides β-catenin. Our study identifies MITF as an oncogenic protein stabilized by Wnt, and describes three novel glycogen synthase kinase 3-regulated phosphorylation sites in this oncogene. This study deepens our knowledge on proliferative stages of melanoma: MITF, multivesicular bodies, and Wnt may form a feedback loop that drives proliferation.
High-throughput plasmid construction using homologous recombination in yeast: its mechanisms and application to protein production for X-ray crystallography
Authors: Mizutani Kimihiko
Published: January 2015

Homologous recombination is a system for repairing the broken genomes of living organisms by connecting two DNA strands at their homologous sequences. Today, homologous recombination in yeast is used for plasmid construction as a substitute for traditional methods using restriction enzymes and ligases. This method has various advantages over the traditional method, including flexibility in the position of DNA insertion and ease of manipulation. Recently, the author of this review reported the construction of plasmids by homologous recombination in the methanol-utilizing yeast Pichia pastoris, which is known to be an excellent expression host for secretory proteins and membrane proteins. The method enabled high-throughput construction of expression systems of proteins using P. pastoris; the constructed expression systems were used to investigate the expression conditions of membrane proteins and to perform X-ray crystallography of secretory proteins. This review discusses the mechanisms and applications of homologous recombination, including the production of proteins for X-ray crystallography.
Precision of working memory for speech sounds
Authors: Joseph Sabine , Iverson Paul , Manohar Sanjay , Fox Zoe , Scott Sophie K. , Husain Masud
Published: January 2015

Memory for speech sounds is a key component of models of verbal working memory (WM). But how good is verbal WM? Most investigations assess this using binary report measures to derive a fixed number of items that can be stored. However, recent findings in visual WM have challenged such “quantized” views by employing measures of recall precision with an analogue response scale. WM for speech sounds might rely on both continuous and categorical storage mechanisms. Using a novel speech matching paradigm, we measured WM recall precision for phonemes. Vowel qualities were sampled from a formant space continuum. A probe vowel had to be adjusted to match the vowel quality of a target on a continuous, analogue response scale. Crucially, this provided an index of the variability of a memory representation around its true value and thus allowed us to estimate how memories were distorted from the original sounds. Memory load affected the quality of speech sound recall in two ways. First, there was a gradual decline in recall precision with increasing number of items, consistent with the view that WM representations of speech sounds become noisier with an increase in the number of items held in memory, just as for vision. Based on multidimensional scaling (MDS), the level of noise appeared to be reflected in distortions of the formant space. Second, as memory load increased, there was evidence of greater clustering of participants’ responses around particular vowels. A mixture model captured both continuous and categorical responses, demonstrating a shift from continuous to categorical memory with increasing WM load. This suggests that direct acoustic storage can be used for single items, but when more items must be stored, categorical representations must be used.
Telling faces together: Learning new faces through exposure to multiple instances
Authors: Andrews Sally , Jenkins Rob , Cursiter Heather , Burton A. Mike
Published: January 2015

We are usually able to recognize novel instances of familiar faces with little difficulty, yet recognition of unfamiliar faces can be dramatically impaired by natural within-person variability in appearance. In a card-sorting task for facial identity, different photos of the same unfamiliar face are often seen as different people. Here we report two card-sorting experiments in which we manipulate whether participants know the number of identities present. Without constraints, participants sort faces into many identities. However, when told the number of identities present, they are highly accurate. This minimal contextual information appears to support viewers in “telling faces together”. In Experiment 2 we show that exposure to within-person variability in the sorting task improves performance in a subsequent face-matching task. This appears to offer a fast route to learning generalizable representations of new faces.
Shared timing variability in eye and finger movements increases with interval duration: Support for a distributed timing system below and above one second
Authors: Karampela Olympia , Holm Linus , Madison Guy
Published: January 2015

The origins of the ability to produce action at will at the hundreds of millisecond to second range remain poorly understood. A central issue is whether such timing is governed by one mechanism or by several different mechanisms, possibly invoked by different effectors used to perform the timing task. If two effectors invoke similar timing mechanisms, then they should both produce similar variability increase with interval duration (interonset interval) and thus adhere to Weber's law (increasing linearly with the duration of the interval to be timed). Additionally, if both effectors invoke the same timing mechanism, the variability of the effectors should be highly correlated across participants. To test these possibilities, we assessed the behavioural characteristics across fingers and eyes as effectors and compared the timing variability between and within them as a function of the interval to be produced (interresponse interval). Sixty participants produced isochronous intervals from 524 to 1431 ms with their fingers and their eyes. High correlations within each effector indicated consistent performance within participants. Consistent with a single mechanism, temporal variability in both fingers and eyes followed Weber's law, and significant correlations between eye and finger variability were found for several intervals. These results can support neither the single clock nor the multiple clock hypotheses but instead suggest a partially overlapping distributed timing system.
Immediate inferences from quantified assertions
Authors: Khemlani Sangeet , Lotstein Max , Trafton J. Gregory , Johnson-Laird P. N.
Published: January 2015

We propose a theory of immediate inferences from assertions containing a single quantifier, such as: All of the artists are bakers; therefore, some of the bakers are artists. The theory is based on mental models and is implemented in a computer program, mReasoner. It predicts three main levels of increasing difficulty: (a) immediate inferences in which the premise and conclusion have identical meanings; (b) those in which the initial mental model of the premise yields the correct conclusion; and (c) those in which only an alternative to the initial model establishes the correct conclusion. These levels of difficulty were corroborated for inferences to necessary conclusions (in a reanalysis of data from Newstead, S. E., & Griggs, R. A. (1983). Drawing inferences from quantified statements: A study of the square of opposition. Journal of Verbal Learning and Verbal Behavior, 22, 535–546), for inferences to modal conclusions, such as, it is possible that all of the bakers are artists (Experiment 1), for inferences with unorthodox quantifiers, such as, most of the artists (Experiment 2), and for inferences about the consistency of pairs of quantified assertions (Experiment 3). The theory also includes three parameters in a stochastic system that predicted quantitative differences in accuracy within the three main sorts of inference.
Stem and Progenitor Cell Therapy for Pulmonary Arterial Hypertension: Effects on the Right Ventricle (2013 Grover Conference Series)
Authors: van der Laarse Arnoud , Cobbaert Christa M. , Umar Soban
Published: January 2015

In experimental animals and in patients with pulmonary arterial hypertension (PAH), a wide spectrum of structural and functional conditions is known that may be responsible for the switch of a state of “compensated” right ventricular (RV) hypertrophy to a state of RV failure. In recent years, therapy with differentiated cells, endothelial progenitor cells, and mesenchymal stem cells has been shown to cause partial or complete reversal of pathological characteristics of PAH. The therapeutic effects of stem or progenitor cell therapy are considered to be (1) paracrine effects from stem or progenitor cells that had engrafted in the myocardium (or elsewhere), by compounds that have anti‐inflammatory, antiapoptotic, and proangiogenic actions and (2) unloading effects on the right ventricle due to stem or progenitor cell–induced decrease in pulmonary vascular resistance and decrease in pulmonary artery pressure.
Doing Well by Doing Good: The Benevolent Halo of Corporate Social Responsibility
Authors: Chernev Alexander , Blair Sean
Published: January 2015

Corporate social responsibility is commonly viewed solely as a tool for enhancing company reputations and engendering goodwill among customers. In contrast, this research shows that the impact of corporate social responsibility can extend beyond public relations and customer goodwill to influence the way consumers evaluate a company’s products. Specifically, this research documents that acts of social goodwill—even when they are unrelated to the company’s core business, as in the case of charitable giving—can alter product perceptions, such that products of companies engaged in prosocial activities are perceived as performing better. More important, the data show that inferences drawn from a company’s prosocial actions are strong enough to alter the product evaluations even when consumers can directly observe and experience the product. The data further show that this effect is a function of the moral undertone of the company’s motivation for engaging in socially responsible behavior and is attenuated when consumers believe that the company’s behavior is driven by self-interest rather than by benevolence. By documenting that social goodwill can benefit consumer perceptions of product performance, these findings show that doing good can indeed translate into doing well.
Influence of provider and urgent care density across different socioeconomic strata on outpatient antibiotic prescribing in the USA
Authors: Klein Eili Y. , Makowsky Michael , Orlando Megan , Hatna Erez , Braykov Nikolay P. , Laxminarayan Ramanan
Published: January 2015

Objectives

Despite a strong link between antibiotic use and resistance, and highly variable antibiotic consumption rates across the USA, drivers of differences in consumption rates are not fully understood. The objective of this study was to examine how provider density affects antibiotic prescribing rates across socioeconomic groups in the USA.

Methods

We aggregated data on all outpatient antibiotic prescriptions filled in retail pharmacies in the USA in 2000 and 2010 from IMS Health into 3436 geographically distinct hospital service areas and combined this with socioeconomic and structural factors that affect antibiotic prescribing from the US Census. We then used fixed-effect models to estimate the interaction between poverty and the number of physician offices per capita (i.e. physician density) and the presence of urgent care and retail clinics on antibiotic prescribing rates.

Results

We found large geographical variation in prescribing, driven in part by the number of physician offices per capita. For an increase of one standard deviation in the number of physician offices per capita there was a 25.9% increase in prescriptions per capita. However, the determinants of the prescription rate were dependent on socioeconomic conditions. In poorer areas, clinics substitute for traditional physician offices, reducing the impact of physician density. In wealthier areas, clinics increase the effect of physician density on the prescribing rate.

Conclusions

In areas with higher poverty rates, access to providers drives the prescribing rate. However, in wealthier areas, where access is less of a problem, a higher density of providers and clinics increases the prescribing rate, potentially due to competition.
Alternative splicing regulates the expression of G9A and SUV39H2 methyltransferases, and dramatically changes SUV39H2 functions
Authors: Mauger Oriane , Klinck Roscoe , Chabot Benoit , Muchardt Christian , Allemand Eric , Batsché Eric
Published: January 2015

Alternative splicing is the main source of proteome diversity. Here, we have investigated how alternative splicing affects the function of two human histone methyltransferases (HMTase): G9A and SUV39H2. We show that exon 10 in G9A and exon 3 in SUV39H2 are alternatively included in a variety of tissues and cell lines, as well as in a different species. The production of these variants is likely tightly regulated because both constitutive and alternative splicing factors control their splicing profiles. Based on this evidence, we have assessed the link between the inclusion of these exons and the activity of both enzymes. We document that these HMTase genes yield several protein isoforms, which are likely issued from alternative splicing regulation. We demonstrate that inclusion of SUV39H2 exon 3 is a determinant of the stability, the sub-nuclear localization, and the HMTase activity. Genome-wide expression analysis further revealed that alternative inclusion of SUV39H2 exon 3 differentially modulates the expression of target genes. Our data also suggest that a variant of G9A may display a function that is independent of H3K9 methylation. Our work emphasizes that expression and function of genes are not collinear; therefore alternative splicing must be taken into account in any functional study.
A minimal ubiquitous chromatin opening element (UCOE) effectively prevents silencing of juxtaposed heterologous promoters by epigenetic remodeling in multipotent and pluripotent stem cells
Authors: Müller-Kuller Uta , Ackermann Mania , Kolodziej Stephan , Brendel Christian , Fritsch Jessica , Lachmann Nico , Kunkel Hana , Lausen Jörn , Schambach Axel , Moritz Thomas , Grez Manuel
Published: January 2015

Epigenetic silencing of transgene expression represents a major obstacle for the efficient genetic modification of multipotent and pluripotent stem cells. We and others have demonstrated that a 1.5 kb methylation-free CpG island from the human HNRPA2B1-CBX3 housekeeping genes (A2UCOE) effectively prevents transgene silencing and variegation in cell lines, multipotent and pluripotent stem cells, and their differentiated progeny. However, the bidirectional promoter activity of this element may disturb expression of neighboring genes. Furthermore, the epigenetic basis underlying the anti-silencing effect of the UCOE on juxtaposed promoters has been only partially explored. In this study we removed the HNRPA2B1 moiety from the A2UCOE and demonstrate efficient anti-silencing properties also for a minimal 0.7 kb element containing merely the CBX3 promoter. This DNA element largely prevents silencing of viral and tissue-specific promoters in multipotent and pluripotent stem cells. The protective activity of CBX3 was associated with reduced promoter CpG-methylation, decreased levels of repressive and increased levels of active histone marks. Moreover, the anti-silencing effect of CBX3 was locally restricted and when linked to tissue-specific promoters did not activate transcription in off target cells. Thus, CBX3 is a highly attractive element for sustained, tissue-specific and copy-number dependent transgene expression in vitro and in vivo.
Long-Term Care Facilities Are Reservoirs for Antimicrobial-Resistant Sequence Type 131 Escherichia coli
Authors: Burgess Mary J. , Johnson James R. , Porter Stephen B. , Johnston Brian , Clabots Connie , Lahr Brian D. , Uhl James R. , Banerjee Ritu
Published: January 2015

Background.  Emerging data implicate long-term care facilities (LTCFs) as reservoirs of fluoroquinolone-resistant (FQ-R) Escherichia coli of sequence type 131 (ST131). We screened for ST131 among LTCF residents, characterized isolates molecularly, and identified risk factors for colonization.

Methods.  We conducted a cross-sectional study using a single perianal swab or stool sample per resident in 2 LTCFs in Olmsted County, Minnesota, from April to July 2013. Confirmed FQ-R E. coli isolates underwent polymerase chain reaction-based phylotyping, detection of ST131 and its H30 and H30-Rx subclones, extended virulence genotyping, and pulsed-field gel electrophoresis (PFGE) analysis. Epidemiological data were collected from medical records.

Results.  Of 133 fecal samples, 33 (25%) yielded FQ-R E. coli, 32 (97%) of which were ST131. The overall proportion with ST131 intestinal colonization was 32 of 133 (24%), which differed by facility: 17 of 41 (42%) in facility 1 vs 15 of 92 (16%) in facility 2 (P = .002). All ST131 isolates represented the H30 subclone, with virulence gene and PFGE profiles resembling those of previously described ST131 clinical isolates. By PFGE, certain isolates clustered both within and across LTCFs. Multivariable predictors of ST131 colonization included inability to sign consent (odds ratio [OR], 4.16 [P = .005]), decubitus ulcer (OR, 4.87 [ P = .04]), and fecal incontinence (OR, 2.59 [P = .06]).

Conclusions.  Approximately one fourth of LTCF residents carried FQ-R ST131 E. coli resembling ST131 clinical isolates. Pulsed-field gel electrophoresis suggested intra- and interfacility transmission. The identified risk factors suggest that LTCF residents who require increased nursing care are at greatest risk for ST131 colonization, possibly due to healthcare-associated transmission.
Functional and Nutritional Characteristics of Soft Wheat Grown in No‐Till and Conventional Cropping Systems
Authors: Park Eun Young , Baik Byung‐Kee , Machado Stephen , Gollany Hero T. , Fuerst E. Patrick
Published: January 2015

The effects of no‐till versus conventional farming practices were evaluated on soft wheat functional and nutritional characteristics, including kernel physical properties, whole wheat composition, antioxidant activity, and end‐product quality. Soft white winter wheat cultivar ORCF 102 was evaluated over a two‐year period from three long‐term replicated no‐till versus conventional tillage studies in Oregon. Wheat from the no‐till cropping systems generally had greater test weight, kernel diameter, and kernel weight and had softer kernels compared with wheat from the conventional tillage systems. Compared with the conventional systems, no‐till whole wheat flour had lower protein and SDS sedimentation volume. Ash content as well as most minerals measured (calcium, copper, iron, magnesium, and zinc), except for manganese and phosphorus, were generally slightly lower in no‐till than in conventional wheat. Whole wheat flour from the no‐till cropping systems generally had slightly lower total phenolic content and total antioxidant capacity. Milling properties, including flour yield, break flour yield, and mill score, were not affected by tillage systems. Refined flour from no‐till systems had lower protein, SDS sedimentation volume, and lactic acid and sucrose solvent retention capacities compared with flour from conventional tillage. No‐till wheat generally had greater sugar‐snap cookie diameter than conventionally tilled wheat. In conclusion, no‐till soft white winter wheat generally had slightly reduced nutritional properties (protein, ash, most minerals, and total antioxidant content) compared with wheat from conventionally tilled systems, and it had equivalent or sometimes superior functional properties for baking cookie‐type products.
ARP2/3-Mediated Actin Nucleation Associated With Symbiosome Membrane Is Essential for the Development of Symbiosomes in Infected Cells of Medicago truncatula Root Nodules
Authors: Gavrin Aleksandr , Jansen Veerle , Ivanov Sergey , Bisseling Ton , Fedorova Elena
Published: January 2015

The nitrogen-fixing rhizobia in the symbiotic infected cells of root nodules are kept in membrane compartments derived from the host cell plasma membrane, forming what are known as symbiosomes. These are maintained as individual units, with mature symbiosomes having a specific radial position in the host cell cytoplasm. The mechanisms that adapt the host cell architecture to accommodate intracellular bacteria are not clear. The intracellular organization of any cell depends heavily on the actin cytoskeleton. Dynamic rearrangement of the actin cytoskeleton is crucial for cytoplasm organization and intracellular trafficking of vesicles and organelles. A key component of the actin cytoskeleton rearrangement is the ARP2/3 complex, which nucleates new actin filaments and forms branched actin networks. To clarify the role of the ARP2/3 complex in the development of infected cells and symbiosomes, we analyzed the pattern of actin microfilaments and the functional role of ARP3 in Medicago truncatula root nodules. In infected cells, ARP3 protein and actin were spatially associated with maturing symbiosomes. Partial ARP3 silencing causes defects in symbiosome development; in particular, ARP3 silencing disrupts the final differentiation steps in functional maturation into nitrogen-fixing units.
Optimizing Trehalose-Based Quantification of Live Eggs in Potato Cyst Nematodes (Globodera rostochiensis and G. pallida)
Authors: Ebrahimi N. , Viaene N. , Moens M.
Published: January 2015

Integrated management of potato cyst nematodes (PCN; Globodera rostochiensis and G. pallida) relies heavily on the determination of cyst population densities in soil as well as the viability of the eggs inside the cysts. This study aimed to optimize a quantitative method to determine the number of viable eggs of PCN based on trehalose present in live eggs. Trehalose was extracted from cysts and from a dilution series of eggs and quantified. More trehalose was detected when cysts were crushed than when left intact. Reaction volumes were adapted to the number of eggs because small reaction volumes hampered an accurate extraction of trehalose. A maximum of 10.5 eggs/μl of reaction volume should be used to obtain a significant linear relationship between detected trehalose content and egg numbers. The sensitivity of the trehalose-based method was evaluated by determining the lowest egg detection limit and was defined as five viable eggs. The reliability of this method was tested by comparing efficacy with that of two commonly used assays, visual assessment and hatching test. The trehalose-based method gave viability results similar to those of the visual assessment, which is time consuming, requires trained personnel, and can involve some subjectivity. The hatching test identified fewer viable eggs than the other two methods. In addition, the viability of dead eggs (heated and naturally dead) was tested. No false-positive results (dead eggs declared viable) were obtained with the trehalose-based method. The robustness of the test was demonstrated by measuring the viability of eggs of PCN in different experiments repeated in time. The viability assessment method based on trehalose proved to be an objective as well as sensitive, reliable, robust, fast, and cheap technique for assessing the number of viable eggs in PCN cysts.
Population Structure of Pythium irregulare, P. ultimum, and P. sylvaticum in Forest Nursery Soils of Oregon and Washington
Authors: Weiland Jerry E. , Garrido Patricia , Kamvar Zhian N. , Espíndola Andrés S. , Marek Stephen M. , Grünwald Niklaus J. , Garzón Carla D.
Published: January 2015

Pythium species are important soilborne pathogens occurring in the forest nursery industry of the Pacific Northwest. However, little is known about their genetic diversity or population structure and it is suspected that isolates are moved among forest nurseries on seedling stock and shared field equipment. In order to address these concerns, a total of 115 isolates of three Pythium species (P. irregulare, P. sylvaticum, and P. ultimum) were examined at three forest nurseries using simple sequence repeat (SSR) and amplified fragment length polymorphism (AFLP) markers. Analyses revealed distinct patterns of intraspecific variation for the three species. P. sylvaticum exhibited the most diversity, followed by P. irregulare, while substantial clonality was found in P. ultimum. For both P. irregulare and P. sylvaticum, but not P. ultimum, there was evidence for significant variation among nurseries. However, all three species also exhibited at least two distinct lineages not associated with the nursery of origin. Finally, evidence was found that certain lineages and clonal genotypes, including fungicide-resistant isolates, are shared among nurseries, indicating that pathogen movement has occurred.
Effect of Lateral Tilt Angle on the Volume of the Abdominal Aorta and Inferior Vena Cava in Pregnant and Nonpregnant Women Determined by Magnetic Resonance Imaging
Authors: Higuchi Hideyuki , Takagi Shunichi , Zhang Kan , Furui Ikue , Ozaki Makoto
Published: January 2015

AbstractAbstract

In 10 singleton parturients at term without anesthesia, the aorta at the mid- to upper lumbar disk levels was not compressed, although the inferior vena cava was. Tilt of 30°, but not 15°, partially relieved the inferior vena caval compression.

Background:

Left-lateral tilt position is used to reduce assumed aortocaval compression by the pregnant uterus.

Methods:

Magnetic resonance images of 10 singleton parturients at full term and 10 healthy nonpregnant women were obtained for measurement of the abdominal aorta and inferior vena cava volume between the L1–L2 disk and L3–L4 disk levels in both the supine and left-lateral tilt positions (15°, 30°, and 45°) maintained by insertion of a 1.5-m-long polyethylene foam placed under the right side of the parturient’s body.

Results:

Aortic volume did not differ significantly between parturients and nonpregnant women in the supine position (12.7 ± 2.0 vs.12.6 ± 2.1 ml, mean ± SD; mean difference, –0.1; 95% confidence interval [CI], −2.0 to 1.9; P = 0.95). Inferior vena cava volume in the supine position was significantly lower in parturients than in nonpregnant women (3.2 ± 3.4 vs.17.5 ± 7.8 ml; mean difference, 14.3; 95% CI, 8.3–20.2; P < 0.001). Aortic volume in parturients did not differ among left-lateral tilt positions. Inferior vena cava volume in the parturients was not increased at 15° (3.0 ± 2.1 ml; mean difference, −0.2; 95% CI, −1.5 to 1.2; P > 0.99), but was significantly increased at 30° (11.5 ± 8.6 ml; mean difference, 8.3; 95% CI, 2.3–14.2; P = 0.009) and 45° (10.9 ± 6.8 ml; mean difference, 7.7; 95% CI, 2.2–13.1; P = 0.015).

Conclusions:

In parturients, the aorta was not compressed, and a 15° left-lateral tilt position did not effectively reduce inferior vena cava compression.