bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intercellular propagated misfolding of wild-type Cu/Zn superoxide dismutase occurs via exosome-dependent and -independent mechanisms
Authors: Grad Leslie I. , Yerbury Justin J. , Turner Bradley J. , Guest William C. , Pokrishevsky Edward , O’Neill Megan A. , Yanai Anat , Silverman Judith M. , Zeineddine Rafaa , Corcoran Lisa , Kumita Janet R. , Luheshi Leila M. , Yousefi Masoud , Coleman Bradley M. , Hill Andrew F. , Plotkin Steven S. , Mackenzie Ian R. , Cashman Neil R. 
Published: February 2014

SignificanceAmyotrophic lateral sclerosis (ALS), an incurable motor neuron disease, is associated with mutation and misfolding of the Cu/Zn superoxide dismutase (SOD1) protein. Prior studies found that mutant misfolded SOD1 can convert wild-type (WT) SOD1 to a misfolded form inside living cells in a prion-like fashion. We now report that misfolded WT SOD1 can be transmitted from cell to cell, and that propagated protein misfolding can be perpetuated. Misfolded SOD1 transmission between cells can be mediated through release and uptake of protein aggregates or via small membrane-bounded transport vesicles called exosomes. These mechanisms may help explain why sporadic ALS, without a known genetic cause, can spread systematically from region to region in a progressive manner.
Toxoplasmaaldolase is required for metabolism but dispensable for host-cell invasion
Authors: Shen Bang , Sibley L. David 
Published: February 2014

SignificancePrevious studies have suggested that aldolase plays an essential role in parasite motility and host-cell invasion by connecting surface-adhesive proteins to the actin–myosin motor of the parasite. However, our studies show thatToxoplasmaaldolase is critical for metabolism but not directly required for parasite motility or invasion. Aldolase-depletedT. gondiicells were sensitive to glucose but showed normal motility and host-cell invasion when grown without glucose, indicating that aldolase does not fulfill an essential role in these important aspects of parasite biology. This conclusion was also supported by studies from adhesin mutants with altered interactions with aldolase in vitro. Taken together, our results force a revision to the current model for host-cell invasion of apicomplexan parasites.
Cortisol shifts financial risk preferences
Authors: Kandasamy Narayanan , Hardy Ben , Page Lionel , Schaffner Markus , Graggaber Johann , Powlson Andrew S. , Fletcher Paul C. , Gurnell Mark , Coates John 
Published: February 2014

Significance
Many influential models in economics, finance, and neurobiology assume risk preferences are a stable trait. In this study we find they are not. We examine the effects of chronic stress on financial risk taking by raising cortisol levels in volunteers over an 8-d period using individually tailored hydrocortisone regimens. We find that they become more risk-averse and that the overweighting of small probabilities becomes more exaggerated among men relative to women. We designed our protocol to maintain ecological validity: The increase in cortisol among participants replicated levels we had previously observed in real traders when faced with uncertainty and market volatility. Physiology-induced shifts in risk preferences may thus be a cause of market instability that has been hitherto overlooked by economists, risk managers, and central bankers.
Chemical-biogeographic survey of secondary metabolism in soil
Authors: Charlop-Powers Zachary , Owen Jeremy G. , Reddy Boojala Vijay B. , Ternei Melinda A. , Brady Sean F. 
Published: February 2014

Significance
A comparative analysis of conserved domain fragments amplified from nonribosomal peptide and polyketide-type gene clusters present in diverse soil microbiomes revealed a link between soil type, species composition, and biosynthetic richness, as well as an unexpected conservation of the meta-secondary metabolome present within microbiomes from similar soil types. Although the functional consequences of these enrichment patterns is not yet clear, it suggests that similar soil types contain functionally related collections of secondary metabolites that likely play conserved roles in the ecology of these soils. This work provides a model for the large-scale extension of molecular phylogenetic-type analyses directly to the study, characterization, and comparison of secondary metabolite biosynthetic gene clusters that remain hidden in diverse soil microbiomes.
Pregnancy without progesterone in horses defines a second endogenous biopotent progesterone receptor agonist, 5α-dihydroprogesterone
Authors: Scholtz Elizabeth L. , Krishnan Shweta , Ball Barry A. , Corbin C. Jo , Moeller Benjamin C. , Stanley Scott D. , McDowell Karen J. , Hughes Austin L. , McDonnell Donald P. , Conley Alan J. 
Published: February 2014

Significance
We have characterized the relative bioactivity of the physiological progestin, dihydroprogesterone (DHP), showing in vivo it maintains equine gestation in the absence of progesterone, generally believed the only steroid capable of supporting pregnancy. DHP activates the equine progesterone receptor (PR) as potently as progesterone itself, and the human PR potently enough to suggest support for human pregnancy. Thus, DHP joins this steroid class as the only other naturally synthesized progestin so defined. This settles five decades of speculation that DHP sustains equine pregnancies in the second half of gestation when circulating progesterone becomes undetectable. Expanding the progestin class in horses reminds us that the limited suite of physiologically relevant sex steroids currently recognized may be incomplete across taxa.
Gene expression differences underlying genotype-by-genotype specificity in a host–parasite system
Authors: Barribeau Seth M. , Sadd Ben M. , du Plessis Louis , Schmid-Hempel Paul 
Published: February 2014

SignificanceSome genotypes of parasites can infect some genotypes of hosts but not others, whereas hosts also vary in susceptibility to a given parasite genotype. Variation in genes important for defenses against parasites could produce this specificity. Here, we find that variation in gene expression depended on both the genotype of the host and the genotype of the parasite. Moreover, we found that bumblebees that were exposed to infectious genotypes of a trypanosome parasite had low gene expression of immune genes but upregulation of genes that control expression. A poorly infecting parasite genotype, however, induced expression of immune genes. These results suggest that variation in the regulation of gene expression may also contribute to producing genotype-by-genotype specificity.
Detecting and visualizing cell phenotype differences from microscopy images using transport-based morphometry
Authors: Basu Saurav , Kolouri Soheil , Rohde Gustavo K. 
Published: February 2014

SignificanceMuch of what is currently known about how cells work has been derived through visual interpretation of microscopy images. Computational methods for image analysis have emerged as quantitative alternatives to visual interpretation. We describe an analysis pipeline for cell image databases that combines statistical pattern recognition with the mathematics of optimal mass transport. The approach is fully automated and does not require the use of ad hoc numerical features. It enables the identification of discriminant phenotypic variations, or biomarkers, between sets of cells (e.g., normal vs. diseased) while at the same time allowing for the visualization of meaningful differences. The approach can be used for fully automated high content screening with a variety of microscopic image modalities.
Circulating giant macrophages as a potential biomarker of solid tumors
Authors: Adams Daniel L. , Martin Stuart S. , Alpaugh R. Katherine , Charpentier Monica , Tsai Susan , Bergan Raymond C. , Ogden Irene M. , Catalona William , Chumsri Saranya , Tang Cha-Mei , Cristofanilli Massimo 
Published: February 2014

Significance
Using microfiltration as a liquid biopsy for the recovery of circulating tumor cells (CTCs) has revealed an accompanying macrophage subset that we use as a highly sensitive biomarker for solid tumors. We supply evidence that this circulating giant cell is a subset of disseminated tumor-associated macrophages capable of binding CTCs in peripheral blood of cancer patients. The presence of this cell expands the concept of using a liquid biopsy not only to indicate cancer presence but also to track cancer treatment effects sequentially using other circulating blood cells. Further, we supply observational evidence hypothesizing a metastasis pathway model in which CTCs migrate with pro-angiogenic macrophages, linking cancer cell intravasation, migration, and extravasation and the formation of metastatic microenvironments.
Dynamic look at DNA unwinding by a replicative helicase
Authors: Lee Seung-Jae , Syed Salman , Enemark Eric J. , Schuck Stephen , Stenlund Arne , Ha Taekjip , Joshua-Tor Leemor 
Published: February 2014

Significance
Precise replication of the genome is essential for maintaining the integrity of genetic information in all forms of life. A key step in this process is the unwinding of the DNA double helix, a subject of intensive research and debate. We took a multifaceted approach to study fundamental mechanisms of helicase function, using the E1 helicase from papillomavirus. Our findings reveal that E1 employs a strand exclusion mechanism to unwind DNA with the N-terminal side leading at the replication fork. Intriguingly, DNA unwinding by E1 is modulated by the origin-recognition domain, suggesting a previously unsuspected role for this domain in regulating helicase activity.
Stochasticity, succession, and environmental perturbations in a fluidic ecosystem
Authors: Zhou Jizhong , Deng Ye , Zhang Ping , Xue Kai , Liang Yuting , Van Nostrand Joy D. , Yang Yunfeng , He Zhili , Wu Liyou , Stahl David A. , Hazen Terry C. , Tiedje James M. , Arkin Adam P. 
Published: February 2014

Significance
The study of ecological succession remains at the core of ecology. Understanding the trajectories and mechanisms controlling ecological succession is crucial to predicting the responses of ecosystems to environmental change and projecting their future states. By definition, deterministic succession is expected under homogeneous abiotic and biotic starting conditions. This study, however, shows that the succession of groundwater microbial communities in response to nutrient amendment is primarily stochastic, but that the drivers controlling biodiversity and succession are dynamic rather than static. By identifying the mechanisms controlling microbial community assembly and succession, this study makes fundamental contribution to the mechanistic understanding essential for a predictive microbial ecology of many systems ranging from microbiomes of humans and plants to natural and managed ecosystems.
Detecting grain rotation at the nanoscale
Authors: Chen Bin , Lutker Katie , Lei Jialin , Yan Jinyuan , Yang Shizhong , Mao Ho-kwang 
Published: February 2014

Significance
The plastic deformation of nanomaterials has long been wrapped in mystery. Grain rotation is suggested to be a dominant mechanism of plastic deformation for ultrafine nanomaterials. However, the in situ observation of grain rotation has been made possible only for coarse-grained materials. Here we report the in situ high-pressure detection of grain rotation at the nanoscale. The surprising observation is that the texture strength of the same-sized platinum drops rapidly with decreasing grain size of the nickel medium, indicating that more active grain rotation occurs in the smaller nickel nanocrystals. Insight into these processes provides a better understanding of the plastic deformation of nanomaterials at a few-nanometer length scale.
Oxygen requirements of the earliest animals
Authors: Mills Daniel B. , Ward Lewis M. , Jones CarriAyne , Sweeten Brittany , Forth Michael , Treusch Alexander H. , Canfield Donald E. 
Published: February 2014

SignificanceThe relationship between the origin of animals and the oxygen content of the atmosphere is a pressing issue in historical geology. Here we challenge the widely held view that low levels of atmospheric oxygen delayed the origin of animals up until 850–542 million years ago. We provide experimental evidence suggesting that the last common ancestor of animals could have thrived in oxygen levels as low as 0.5% to 4% of present atmospheric levels, which were likely met on Earth well before animals evolved. This was achieved by observing the survival of sponges, basal animals similar to the earliest metazoans, under low-oxygen conditions in the laboratory. These results encourage us to reconsider the environmental constraints on the origin of animal life.
Local immunostimulation leading to rejection of accepted male skin grafts by female mice as a model for cancer immunotherapy
Authors: Bourdeaux Christophe , Lurquin Christophe , Jacquemart Isabelle , Lethé Bernard , Brasseur Francis , van Baren Nicolas , Baurain Jean-François , Dyson Julian , Van Snick Jacques , Uyttenhove Catherine , Boon Thierry 
Published: February 2014

SignificanceMany cancer patients mount a spontaneous T-lymphocyte response against their tumor. In metastatic progressing patients, this response has evidently been incomplete. Moreover, it has stalled, and an immunosuppressive environment appears to be present within the tumor. This may constitute a major factor preventing success of immunotherapies such as antitumoral vaccination. Similar stalled responses are occasionnally observed in the area of tissue transplantation. In a mouse strain named CBA, this phenomenon is observed when male skin is grafted onto females. We used this system to find combinations of cytokines and Toll receptor ligands that, when applied locally, relieve the immunosuppression and reactivate the response. The combinations reported here may prove generally useful to boost the efficacy of cancer immunotherapy.
Dissociation of the trimeric gp41 ectodomain at the lipid–water interface suggests an active role in HIV-1 Env-mediated membrane fusion
Authors: Roche Julien , Louis John M. , Grishaev Alexander , Ying Jinfa , Bax Adriaan 
Published: February 2014

Significance
Infection by HIV-1 requires fusion of viral and host cell membranes, a process mediated by viral protein gp41. Although extensive structural detail on both pre- and postfusion gp41 states is available from X-ray crystallography and cryo-EM studies, little is known about the actual transition. This NMR study of a trimeric gp41 ectodomain, which connects viral and host cell membranes in the prefusion state, suggests a fusion model, where this domain unzippers from opposite ends because of the affinity of its two α-helices for viral and host cell membranes. In this model, the change in orientation of the ectodomain helices, which is associated with membrane binding, provides the driving force that pulls the membranes into the close juxtaposition required for fusion.
Inhibition of Cullin-RING E3 ubiquitin ligase 7 by simian virus 40 large T antigen
Authors: Hartmann Thomas , Xu Xinsong , Kronast Mira , Muehlich Susanne , Meyer Kathleen , Zimmermann Wolfgang , Hurwitz Jerard , Pan Zhen-Qiang , Engelhardt Stefan , Sarikas Antonio 
Published: February 2014

Significance
Simian virus 40 (SV40) large tumor antigen (LT) is a viral oncoprotein with the ability to induce tumors by inhibition of cellular tumor suppressors such as p53 and members of the retinoblastoma protein family. Here we present evidence for a role of SV40 LT in suppressing the activity of Cullin-RING E3 ubiquitin ligase 7 in mediating the ubiquitin-dependent degradation of insulin receptor substrate 1 (IRS1). This SV40 LT-mediated protection of IRS1 leads to enhanced activation of promitogenic downstream signaling pathways AKT and Erk mitogen-activated pathway kinase, which may contribute to viral-induced oncogenic transformation.
The potential impact of climate change on the infectious diseases of commercially important shellfish populations in the Irish Sea—a review
Authors: Rowley Andrew F. , Cross Maud E. , Culloty Sarah C. , Lynch Sharon A. , Mackenzie Clara L. , Morgan Emer , O'Riordan Ruth M. , Robins Peter E. , Smith Amanda L. , Thrupp Tara J. , Vogan Claire L. , Wootton Emma C. , Malham Shelagh K. 
Published: February 2014

AbstractThe Irish Sea and surrounding regions are a rich source of shellfish production as a result of captive fishing and aquaculture. Key species produced include lobsters (Homarus gammarus), edible crabs (Cancer pagurus), langoustines (Nephrops norvegicus), flat oysters (Ostrea edulis), cockles (Cerestoderma edule) and blue mussels (Mytilus edulis). The role played by infectious disease in limiting the sustainability of the production of these species is largely neglected. This review summarizes our knowledge of the key diseases of commercially important crustaceans and bivalve molluscs and attempts to determine their role in limiting the population of animals available for food production both at present and in the future. It shows that the key diseases threatening the sustainability of shellfish production are bitter crab disease in langoustines and edible crabs, and a wide range of diseases caused by micro- and macro-parasites in some bivalve molluscs including oysters and cockles. Oceanographic models are also employed to predict how changes in climate over the next half century may affect these key diseases and their hosts as found in the Irish Sea. It is concluded that the paucity of information on the potential transfer of some disease agents in pelagic larval stages of hosts and vectors is a major hurdle in predicting how some changes in environmental conditions may influence the prevalence and severity of shellfish diseases in coming years.
Inhibition of acid‐sensing ion channel currents by propofol in rat dorsal root ganglion neurons
Authors: Lei Zhen , Li Xiaoyu , Wang Guizhi , Fei Jianchun , Meng Tao , Zhang Xinyu , Yu Jingya , Yu Jingui , Li Jingxin 
Published: February 2014

Summary

Acid‐sensing ion channels (ASICs), part of the epithelial sodium channel/degenerin family, are activated by extracellular protons. The ASICs play a significant role in the acidosis‐mediated perception of pain. The anaesthetic agent propofol also exerts antinociceptive effects, but the underlying mechanisms for this effect are not clear.

We used whole‐cell patch clamping to investigate the effect of propofol on proton‐gated currents in: (i) rat dorsal root ganglion (DRG) neurons; and (ii) HEK293 cells transfected with either ASIC1a or ASIC3.

Propofol inhibited the amplitude of proton‐gated currents in DRG neurons, but did not change the sensitivity of ASICs to H+. Notably, propofol altered acid‐evoked excitability of rat DRG neurons and decreased the number of action potentials induced by acid stimuli. In addition, we demonstrated that propofol inhibited ASICs by directly binding with these channels in HEK293 cells.

These results suggest that propofol inhibits proton‐gated currents in DRG neurons and that inhibition of proton‐gated currents explains, in part, the antinociceptive effects of propofol in primary afferent neurons.
Bitter tastants induce relaxation of rat thoracic aorta precontracted with high K+
Authors: Sai Wen‐Bo , Yu Meng‐Fei , Wei Ming‐Yu , Lu Zhongju , Zheng Yun‐Min , Wang Yong‐Xiao , Qin Gangjian , Guo Donglin , Ji Guangju , Shen Jinhua , Liu Qing‐Hua 
Published: February 2014

Summary

It has been reported that bitter tastants decrease blood pressure and relax precontracted vascular smooth muscle. However, the underlying mechanisms remain unclear. The aim of the present study was to determine the mechanism underlying the vasorelaxant effect of the bitter tastants.

Thoracic aortic rings were isolated from Wistar rats and contractions were measured using an isometric myograph. Intracellular Ca2+ ([Ca2+]i) in single rat thoracic aortic smooth muscle cells was recorded by calcium imaging. Calcium currents in single cells were recorded using patch‐clamp techniques. High K+ (140 mmol/L) induced contractions in rat thoracic aortic rings that were inhibited by 3 mmol/L chloroquine, 3 mmol/L denatonium and 10 μmol/L nifedipine. In single rat thoracic aortic smooth muscle cells, high K+ increased [Ca2+]i and this effect was also blocked by 3 mmol/L chloroquine and 10 μmol/L nifedipine. Under Ca2+‐free conditions, high K+ failed to induce contractions in rat thoracic aortic rings. On its own, chloroquine had no effect on the muscle tension of rat aortic rings and [Ca2+]i. The vasorelaxant effects of chloroquine on precontracted rat thoracic aortic rings were not altered by either 1 μg/mL pertussis toxin (PTX), an inhibitor of Gαo/i ‐protein, or 1 mmol/L gallein, an inhibitor of Gβγ‐protein. The results of patch‐clamp analysis in single cells indicate that 1 mmol/L chloroquine blocks voltage‐dependent L‐type Ca2+ channel (VDLCC) currents from both extracellular and intracellular sides.

Together, the results indicate that chloroquine can block VDLCC, independent of PTX‐ and gallein‐sensitive G‐proteins, resulting in relaxation of high K+‐precontracted thoracic aortic smooth muscle.
The Rise ofChina and Its Implications for the Global Economy: Evidence from a Global Vector Autoregressive Model
Authors: Feldkircher Martin , Korhonen Iikka 
Published: February 2014

AbstractThis paper studies empirically the role ofChina in the world economy. We examine both the way theChinese economy reacts to exchange rate shocks and the repercussions for the world economy of an output shock emanating fromChina. Based on a global vector autoregressive model and a new data set that excels in country coverage and covers the most recent time period including the global financial crisis, our results are threefold: First, we show that a +1% shock toChinese output translates to a permanent increase of 1.1% inChinese realGDPand a 0.1% to 0.5% rise in output for most large economies. Second, to benchmark the shock toChinese output, we examine the response to a +1% shock toUS GDP. The results show that theUSeconomy remains dominant in the world economy, as output rises in other advanced economies by 0.6 to 1%. By contrast,China seems to be little affected by theUSshock. Finally, we are the first to assess the impact of a real appreciation of the renminbi versus theUSdollar in a global model. Our results indicate that real appreciation of the renminbi decreases the level ofChineseGDPslightly and the long‐run effect is also negative for many countries exporting (e.g. raw materials) toChina.