bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying Antigenic Relationships among the Lyssaviruses
Authors: Horton D. L. , McElhinney L. M. , Marston D. A. , Wood J. L. N. , Russell C. A. , Lewis N. , Kuzmin I. V. , Fouchier R. A. M. , Osterhaus A. D. M. E. , Fooks A. R. , Smith D. J. 
Published: September 2010

ABSTRACT
All lyssaviruses cause fatal encephalitis in mammals. There is sufficient antigenic variation within the genus to cause variable vaccine efficacy, but this variation is difficult to characterize quantitatively: sequence analysis cannot yet provide detailed antigenic information, and antigenic neutralization data have been refractory to high-resolution robust interpretation. Here, we address these issues by using state-of-the-art antigenic analyses to generate a high-resolution antigenic map of a global panel of 25 lyssaviruses. We compared the calculated antigenic distances with viral glycoprotein ectodomain sequence data. Although 67% of antigenic variation was predictable from the glycoprotein amino acid sequence, there are in some cases substantial differences between genetic and antigenic distances, thus highlighting the risk of inferring antigenic relationships solely from sequence data at this time. These differences included epidemiologically important antigenic differences between vaccine strains and wild-type rabies viruses. Further, we quantitatively assessed the antigenic relationships measured by using rabbit, mouse, and human sera, validating the use of nonhuman experimental animals as a model for determining antigenic variation in humans. The use of passive immune globulin is a crucial component of rabies postexposure prophylaxis, and here we also show that it is possible to predict the reactivity of immune globulin against divergent lyssaviruses.
Functional Sindbis Virus Replicative Complexes Are Formed at the Plasma Membrane
Authors: Frolova Elena I. , Gorchakov Rodion , Pereboeva Larisa , Atasheva Svetlana , Frolov Ilya 
Published: September 2010

ABSTRACT
Formation of virus-specific replicative complexes (RCs) in infected cells is one of the most intriguing and important processes that determine virus replication and ultimately their pathogenesis on the molecular and cellular levels. Alphavirus replication was known to lead to formation of so-called type 1 cytopathic vacuoles (CPV1s), whose distinguishing feature is the presence of numerous membrane invaginations (spherules) and accumulation of viral nonstructural proteins (nsPs) at the cytoplasmic necks of these spherules. These CPV1s, modified endosomes and lysosomes, were proposed as the sites of viral RNA synthesis. However, our recent studies have demonstrated that Sindbis virus (SINV)-specific, double-stranded RNA (dsRNA)- and nonstructural protein (nsP)-containing RCs are initially formed at the plasma membrane. In this new study, we present extensive evidence that (i) in cells of vertebrate origin, at early times postinfection, viral nsPs colocalize with spherules at the plasma membrane; (ii) viral dsRNA intermediates are packed into membrane spherules and are located in their cavities on the external surface of the plasma membrane; (iii) formation of the membrane spherules is induced by the partially processed nonstructural polyprotein P123 and nsP4, but synthesis of dsRNA is an essential prerequisite of their formation; (iv) plasma membrane-associated dsRNA and protein structures are the active sites of single-stranded RNA (ssRNA) synthesis; (v) at late times postinfection, only a small fraction of SINV nsP-containing complexes are relocalized into the cytoplasm on the endosome membrane. (vi) pharmacological drugs inhibiting different endocytotic pathways have either only minor or no negative effects on SINV RNA replication; and (vii) in mosquito cells, at any times postinfection, dsRNA/nsP complexes and spherules are associated with both endosomal/lysosomal and plasma membranes, suggesting that mechanisms of RC formation may differ in cells of insect and vertebrate origins.
The biostratigraphical distribution of earliest tetrapods (Late Devonian): a revised version with comments on biodiversification
Authors: Blieck A. , Clément G. , Streel M. 
Published: September 2010

Abstract
The 13 presently known genera of Late Devonian tetrapods are situated in the recently completed miospore zonation of Western Gondwana and Euramerica, in relation to the standard conodont zonation. Some of them are still unprecisely dated. The stratigraphic sequences of East Greenland, North China and East Australia are briefly reviewed to discuss the age of the tetrapods collected there and to analyse consequences in relation to the Frasnian–Famennian and Devonian–Carboniferous boundaries. Two episodes of biodiversification seem to have occurred: the first in the Frasnian and the second in the late and latest Famennian. Due to the currently known fossil evidence, the consensus scenario advocates a late Middle Devonian to early Late Devonian origin of tetrapods on the Old Red Sandstone Continent (Euramerica) at a time of warm climate and recovering atmospheric oxygen level during the building of a pre-Pangaean configuration of landmasses.
Osmotic tolerance and habitat of early stegocephalians: indirect evidence from parsimony, taphonomy, palaeobiogeography, physiology and morphology
Authors: Laurin M. , Soler-Gijón R. 
Published: September 2010

Abstract
There are probably many reasons for the widespread belief that temnospondyls and other early stegocephalians were largely restricted to freshwater, but three of the contributing factors will be discussed below. First, temnospondyls have been called amphibians (and thought to be more closely related to extant amphibians than to amniotes). Some authors may have simply concluded that, like extant amphibians, temnospondyls could not live in oceans and seas. Second, under some phylogenies, temnospondyls are more closely related to anurans (and possibly urodeles) than to gymnophionans and could be expected, for parsimony reasons, to share the intolerance of all extant amphibians to saltwater. Similarly, ‘lepospondyls’ are often thought to be more closely related to gymnophionans than to anurans, and could also be expected to lack saltwater tolerance. Third, extant lungfishes live exclusively in freshwater, and early sarcopterygians have long been thought to share this habitat. These interpretations probably explain the widespread belief that early amphibians and early stem-tetrapods were largely restricted to freshwater. However, these three interpretations have been refuted or questioned by recent investigations. A review of the evidence suggests that several (perhaps most) early stegocephalians tolerated saltwater, even although they also lived in freshwater.
Palaeogeographic and palaeoclimatic considerations based on Ordovician to Lochkovian vegetation
Authors: Steemans Philippe , Wellman Charles H. , Gerrienne Philippe 
Published: September 2010

Abstract
This paper summarizes research on Ordovician to Lochkovian vegetation development in a palaeogeographic framework. A terrestrialization model is described. Palaeogeographic maps are modified to explain the vegetation migrations. Land plants first evolved on the Gondwana plate and colonized Avalonia and later Laurentia and Baltica when those plates were in close proximity (Ashgill–Llandovery). South America was colonized during the Llandovery following the collapse of the ice sheet centred on the southern pole which had previously been an impassable barrier for miospores. An Aeronian–Telychian event related to the global early Silurian transgression modified the vegetation by destroying biotopes where the earliest vegetation was thriving. During the regression, trilete spore-producing plants appear to have been more able to respond to environmental changes and dominated the vegetation from the Homerian. Cryptospore-producing plants could survive under a wide range of climates, which helped them to survive during the Hirnantian glaciation. On the contrary, the earliest trilete spore-producing plants were probably climatically restricted, as suggested by latitudinal variation in assemblage composition. By the end of the Silurian, there were several phytogeographic units. Information on the earliest vegetation favours palaeogeographic reconstructions where plates are in close proximity.
First record of
Rellimia
Leclercq & Bonamo (Aneurophytales) from Gondwana, with comments on the earliest lignophytes
Authors: Gerrienne P. , Meyer-Berthaud B. , Lardeux H. , Régnault S. 
Published: September 2010

Abstract

The lignophytes (Embryophytes that possess a bifacial cambium) evolved during the Devonian period and include seed plants. Their advent was a major event in the history of life and had a profound impact on terrestrial environments. Recent reinvestigations of a Devonian locality, Dechra Aït Abdallah in Central Morocco, led to the discovery of a rich assemblage of fossil plants and Tentaculita. This paper focuses on a single specimen of the lignophyte
Rellimia
Leclercq & Bonamo.
Rellimia
(Aneurophytales) is a monospecific genus reported from a large number of Middle Devonian localities from western Europe (Belgium, Czech Republic, Germany and Scotland) and America. Its fertile organs are highly distinctive and borne helically on branches. They consist of a basal stalk that dichotomizes once near the base, the resulting branches dividing pinnately and bearing elongated sporangia terminally on ultimate divisions. According to the late Emsian age indicated by our sample of Tentaculita, this Moroccan specimen is to date the earliest representative of both the genus and the lignophytes. If confirmed, this occurrence suggests a possible origin of the Aneurophytalean lignophytes in Gondwana and their rapid and widespread colonization in the Middle Devonian towards Laurussia.
Embelin Suppresses Osteoclastogenesis Induced by Receptor Activator of NF-κB Ligand and Tumor CellsIn vitrothrough Inhibition of the NF-κB Cell Signaling Pathway
Authors: Reuter Simone , Prasad Sahdeo , Phromnoi Kanokkarn , Kannappan Ramaswamy , Yadav Vivek R. , Aggarwal Bharat B. 
Published: September 2010

AbstractMost patients with cancer die not because of the tumor in the primary site, but because it has spread to other sites. Common tumors, such as breast, multiple myeloma, and prostate tumors, frequently metastasize to the bone. It is now well recognized that osteoclasts are responsible for the osteolysis observed in bone metastases of the tumor. Receptor activator of NF-κB ligand (RANKL), a member of the tumor necrosis factor superfamily and an activator of the NF-κB signaling pathway, has emerged as a major mediator of bone loss, commonly associated with cancer and other chronic inflammatory diseases. Embelin (2,5-dihydroxy-3-undecyl-1,4-benzoquinone), derived from the Ayurvedic medicinal plant Embelia ribes, has been shown to bind and inhibit X-linked inhibitor of apoptosis protein and inhibit inflammatory pathways. We investigated whether embelin could inhibit osteoclastogenesis-associated bone loss induced by RANKL and by tumor cells in vitro. We found that embelin suppressed the RANKL-induced differentiation of monocytes into osteoclasts. This benzoquinone also suppressed the osteoclastogenesis induced by multiple myeloma and by breast cancer cells. This effect of embelin correlated with the suppression of NF-κB activation and inhibition of IκBα phosphorylation and IκBα degradation. Inhibition of IκBα phosphorylation was due to the inhibition of IκBα kinase (IKK) activation. Furthermore, by using an inhibitor of the IKKγ or NF-κB essential modulator (NEMO), the regulatory component of the IKK complex, we showed that the NF-κB signaling pathway is mandatory for RAW 264.7 cell differentiation into osteoclasts. Thus, embelin, an inhibitor of RANKL-induced NF-κB activation has great potential as a therapeutic agent for osteoporosis and cancer-linked bone loss. Mol Cancer Res; 8(10); 1425–36. ©2010 AACR.
Dobutamine-Induced Improvement in Inferior Myocardial Contractile Function Predicts Reduction in Functional Mitral Regurgitation
Authors: Tatsumi Kazuhiro , Kawai Hiroya , Sugiyama Daisuke , Norisada Kazuko , Kataoka Toshiya , Onishi Tetsuari , Tanaka Hidekazu , Hirata Ken-ichi 
Published: September 2010

Background—
Left ventricular (LV) remodeling can increase tethering force to mitral valve and functional mitral regurgitation (FMR). Because the relationship between FMR and regional myocardial function has not been quantitatively evaluated, we conducted a quantitative investigation of this association.

Methods and Results—

The effective regurgitant orifice (ERO) of FMR in 51 patients with depressed LV ejection fraction (32±9%) secondary to ischemic or nonischemic cardiomyopathy was compared with mitral deformation (valve and annulus), global LV remodeling (volume indices, function, and sphericity), and regional myocardial contractile function, as assessed by longitudinal peak systolic strain rate (Ssr) in LV anterior, anteroseptal, inferoseptal, inferior, inferolateral, and anterolateral segments at rest. Low-dose dobutamine (10 μg/kg per minute)-induced changes in ERO were compared with changes in the variables. Multivariable analysis identified the predictors of ERO at rest as mitral valvular tenting (β=0.062;
P
<0.001), Ssr in the inferior segment (inferior Ssr) (β=−0.178;
P
<0.001), and LV sphericity (β=0.414;
P
=0.001) and the predictors of valvular tenting at rest as inferior Ssr (β=−1.680;
P
<0.001), LV end-systolic volume index (β=0.022;
P
=0.001), and LV sphericity (β=3.886;
P
=0.012). Furthermore, dobutamine-induced reduction in ERO was predicted by reduction in valvular tenting (β=0.087;
P
<0.001) and increase in inferior Ssr (β=−0.082;
P
<0.001), and dobutamine-induced reduction in valvular tenting was predicted by increase in inferior Ssr (β=−0.860;
P
<0.001).

Conclusions—
Inferior regional myocardial dysfunction was quantitatively associated with mitral valvular tenting and FMR. Moreover, improvement with dobutamine of inferior myocardial contractile function attenuated valvular tenting and FMR. Inferior myocardial contractile function can affect the configuration of the mitral apparatus and predict FMR severity.
Remote Ischemic Conditioning in Patients With Myocardial Infarction Treated With Primary Angioplasty
Authors: Munk Kim , Andersen Niels Holmark , Schmidt Michael Rahbek , Nielsen Soren Steen , Terkelsen Christian Juhl , Sloth Erik , Bøtker Hans Erik , Nielsen Torsten Toftegaard , Poulsen Steen Hvitfeldt 
Published: September 2010

Background—
We have found that remote ischemic conditioning (rIC), adjunctive to primary angioplasty, increases myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI) and extensive myocardial area at risk (AAR). The present substudy aimed to evaluate the short-term effects of rIC on left ventricular (LV) function.

Methods and Results—

Patients with a first STEMI were randomized to rIC (4 cycles of 5 minutes upper-limb ischemia) during transfer to primary percutaneous coronary intervention (pPCI) (n=123) versus pPCI alone (n=119). Ejection fraction (EF), LV volumes, (2D and 3D echocardiography and myocardial perfusion imaging), and speckle-tracking global longitudinal strain were compared between treatment groups. There was no significant difference in LV function at day 1 (EF-2D, 0.51±0.10 versus 0.49±0.10;
P
=0.22) and after 30 days (EF-2D, 0.54±0.08 versus 0.53±0.10) between the rIC and the pPCI-alone groups. In patients with extensive AAR ≥35% of LV (n=53), EF after 30 days was higher after rIC than after pPCI alone (EF-2D, 0.51±0.07 versus 0.46±0.09;
P
=0.05). In patients with anterior infarction (n=97), rIC preserved LV function on day 1 (EF-2D, 0.51±0.11 versus 0.46±0.11;
P
=0.03) and persistently after 30 days (EF-2D, 0.55±0.08 versus 0.50±0.11;
P
=0.04; EF-myocardial perfusion imaging, 0.55±0.10 versus 0.49±0.12;
P
=0.02). These patients had similar AAR, whereas rIC reduced infarct size from 16% to 7% of LV (
P
=0.01).

Conclusions—
Although no significant overall effect was observed, rIC seemed to result in modest improvement in LV function in high-risk patients prone to develop large myocardial infarcts. These results need to be confirmed in larger trials.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00435266.
A Shovel With a Perforated Blade Reduces Energy Expenditure Required for Digging Wet Clay
Authors: Harivanam Sridhar , Marklin Richard W. , Papanek Paula E. , Cariapa Vikram 
Published: September 2010

Objective: A shovel with a blade perforated with small holes was tested to see whether a worker would use less whole-body energy to dig wet clay than with a shovel with an opaque blade. Background: A perforated shovel is hypothesized to require less whole-body energy on the basis of adhesion theory; a smaller surface area would require less physical effort to dig and release soil from the blade. Method: The study involved 13 workers from an electric utility who dug wet clay with two 1.5-m long-handled point shovels, which differed only in blade design (perforated and opaque). Oxygen consumption was measured with a portable system while each worker dug wet clay at a self-regulated pace for 10 min. Results: There was no significant difference in number of scoops dug during the 10-min sessions, but workers dug 9.5% more weight of clay with the perforated shovel than with the conventional shovel (404 kg vs. 369 kg, respectively). Furthermore, stable oxygen uptake normalized to weight of participant and to the weight of clay dug revealed that participants expended 11.7% less relative energy per kilogram of clay dug with the perforated shovel. Conclusion: A point shovel with a perforated blade is recommended for digging and shoveling wet clay. However, the extra weight that workers chose to dig with the perforated shovel may increase the loading on the spine and may offset the metabolic advantages. Application: Manual shoveling is a common task, and workers may experience less whole-body and muscle fatigue when using a perforated shovel.
Transferrin receptor 2 is a component of the erythropoietin receptor complex and is required for efficient erythropoiesis
Authors: Forejtnikovà Hana , Vieillevoye Maud , Zermati Yael , Lambert Mireille , Pellegrino Rosa Maria , Guihard Soizic , Gaudry Muriel , Camaschella Clara , Lacombe Catherine , Roetto Antonella , Mayeux Patrick , Verdier Frédérique 
Published: September 2010

AbstractErythropoietin (Epo) is required for erythroid progenitor differentiation. Although Epo crosslinking experiments have revealed the presence of Epo receptor (EpoR)–associated proteins that could never be identified, EpoR is considered to be a paradigm for homodimeric cytokine receptors. We purified EpoR-binding partners and identified the type 2 transferrin receptor (TfR2) as a component of the EpoR complex corresponding to proteins previously detected in cross-linking experiments. TfR2 is involved in iron metabolism by regulating hepcidin production in liver cells. We show that TfR2 and EpoR are synchronously coexpressed during the differentiation of erythroid progenitors. TfR2 associates with EpoR in the endoplasmic reticulum and is required for the efficient transport of this receptor to the cell surface. Erythroid progenitors from TfR2−/−mice show a decreased sensitivity to Epo and increased circulating Epo levels. In human erythroid progenitors, TfR2 knockdown delays the terminal differentiation. Erythroid cells produce growth differentiation factor-15, a cytokine that suppresses hepatic hepcidin production in certain erythroid diseases such as thalassemia. We show that the production of growth differentiation factor-15 by erythroid cells is dependent on both Epo and TfR2. Taken together, our results show that TfR2 exhibits a non hepatic function as a component of the EpoR complex and is required for efficient erythropoiesis.
On the Choice and Number of Microarrays for Transcriptional Regulatory Network Inference
Authors: Cosgrove Elissa J , Gardner Timothy S , Kolaczyk Eric D 
Published: September 2010

AbstractBackgroundTranscriptional regulatory network inference (TRNI) from large compendia of DNA microarrays has become a fundamental approach for discovering transcription factor (TF)-gene interactions at the genome-wide level. In correlation-based TRNI, network edges can in principle be evaluated using standard statistical tests. However, while such tests nominally assume independent microarray experiments, we expect dependency between the experiments in microarray compendia, due to both project-specific factors (e.g., microarray preparation, environmental effects) in the multi-project compendium setting and effective dependency induced by gene-gene correlations. Herein, we characterize the nature of dependency in anEscherichia colimicroarray compendium and explore its consequences on the problem of determining which and how many arrays to use in correlation-based TRNI.ResultsWe present evidence of substantial effective dependency among microarrays in this compendium, and characterize that dependency with respect to experimental condition factors. We then introduce a measureneffof the effective number of experiments in a compendium, and find that corresponding to the dependency observed in this particular compendium there is a huge reduction in effective sample size i.e.,neff= 14.7 versusn= 376. Furthermore, we found that theneffof select subsets of experiments actually exceededneffof the full compendium, suggesting that the adage 'less is more' applies here. Consistent with this latter result, we observed improved performance in TRNI using subsets of the data compared to results using the full compendium. We identified experimental condition factors that trend with changes in TRNI performance andneff, including growth phase and media type. Finally, using the set of known E. coli genetic regulatory interactions from RegulonDB, we demonstrated that false discovery rates (FDR) derived fromneff-adjusted p-values were well-matched to FDR based on the RegulonDB truth set.ConclusionsThese results support utilization ofneffas a potent descriptor of microarray compendia. In addition, they highlight a straightforward correlation-based method for TRNI with demonstrated meaningful statistical testing for significant edges, readily applicable to compendia from any species, even when a truth set is not available. This work facilitates a more refined approach to construction and utilization of mRNA expression compendia in TRNI.