bluuebunny/crossref_metadata_2025_split huggingface dataset:
MOST: a software environment for constraint-based metabolic modeling and strain design
Authors: Kelley James J. , Lane Anatoliy , Li Xiaowei , Mutthoju Brahmaji , Maor Shay , Egen Dennis , Lun Desmond S. 
Published: October 2014

Summary: MOST (metabolic optimization and simulation tool) is a software package that implements GDBB (genetic design through branch and bound) in an intuitive user-friendly interface with excel-like editing functionality, as well as implementing FBA (flux balance analysis), and supporting systems biology markup language and comma-separated values files. GDBB is currently the fastest algorithm for finding gene knockouts predicted by FBA to increase production of desired products, but GDBB has only been available on a command line interface, which is difficult to use for those without programming knowledge, until the release of MOST.
Availability and implementation: MOST is distributed for free on the GNU General Public License. The software and full documentation are available at http://most.ccib.rutgers.edu/.
Contact: dslun@rutgers.edu.
IntSide: a web server for the chemical and biological examination of drug side effects
Authors: Juan-Blanco Teresa , Duran-Frigola Miquel , Aloy Patrick 
Published: October 2014

Summary: Drug side effects are one of the main health threats worldwide, and an important obstacle in drug development. Understanding how adverse reactions occur requires knowledge on drug mechanisms at the molecular level. Despite recent advances, the need for tools and methods that facilitate side effect anticipation still remains. Here, we present IntSide, a web server that integrates chemical and biological information to elucidate the molecular mechanisms underlying drug side effects. IntSide currently catalogs 1175 side effects caused by 996 drugs, associated with drug features divided into eight categories, belonging to either biology or chemistry. On the biological side, IntSide reports drug targets and off-targets, pathways, molecular functions and biological processes. From a chemical viewpoint, it includes molecular fingerprints, scaffolds and chemical entities. Finally, we also integrate additional biological data, such as protein interactions and disease-related genes, to facilitate mechanistic interpretations.
Availability and implementation: Our data and web resource are available online (http://intside.irbbarcelona.org/).
Contact: patrick.aloy@irbbarcelona.org
Supplementary information: Supplementary Data are available at Bioinformatics online.
Therapeutic uses of anti-α4-integrin (anti-VLA-4) antibodies in multiple sclerosis
Authors: Schwab Nicholas , Schneider-Hohendorf Tilman , Wiendl Heinz 
Published: October 2014

AbstractMultiple sclerosis (MS) is a disorder of putative autoimmune origin, where immune cells invade the central nervous system and cause damage by attacking the myelin sheath of nerve cells. The blockade of the integrin very late antigen-4 (VLA-4) with the monoclonal antibody natalizumab has become the most effective therapy against MS since its approval in 2004. It is assumed that the inhibition of VLA-4-mediated immune cell adhesion to the endothelium of the blood–brain barrier (BBB) alleviates pathogenic processes of MS and, therefore, reduces disease severity and burden. Not all approaches to treat additional immune-mediated disorders (e.g. Rasmussen encephalitis and neuromyelitis optica) with natalizumab have been successful, but allowed researchers to gain additional insight into mechanisms of specific immune cell subsets’ migration through the BBB in the human system. While the long-term efficacy and general tolerability of natalizumab in MS are clear, the over 400 cases of natalizumab-associated progressive multifocal leukoencephalopathy (PML) have been of great concern and methods of risk stratification in patients have become a major area of research. Modern risk stratification includes established factors such as treatment duration, previous immune-suppressive therapy, and anti-John Cunningham virus (JCV) antibody seropositivity, but also experimental factors such as anti-JCV antibody titers and levels of L-selectin. Today, anti-VLA-4 therapy is reserved for patients with highly active relapsing-remitting MS and patients are monitored closely for early signs of potential PML.
On the observability of coupled dark energy with cosmic voids
Authors: Sutter P. M. , Carlesi Edoardo , Wandelt Benjamin D. , Knebe Alexander 
Published: October 2014

Abstract
Taking N-body simulations with volumes and particle densities tuned to match the sloan digital sky survey DR7 spectroscopic main sample, we assess the ability of current void catalogues to distinguish a model of coupled dark matter–dark energy from Λ cold dark matter cosmology using properties of cosmic voids. Identifying voids with the vide toolkit, we find no statistically significant differences in the ellipticities, but find that coupling produces a population of significantly larger voids, possibly explaining the recent result of Tavasoli et al. In addition, we use the universal density profile of Hamaus et al. to quantify the relationship between coupling and density profile shape, finding that the coupling produces broader, shallower, undercompensated profiles for large voids by thinning the walls between adjacent medium-scale voids. We find that these differences are potentially measurable with existing void catalogues once effects from survey geometries and peculiar velocities are taken into account.
Magnetic spiral arms and galactic outflows
Authors: Chamandy Luke , Shukurov Anvar , Subramanian Kandaswamy 
Published: October 2014

Abstract
Galactic magnetic arms have been observed between the gaseous arms of some spiral galaxies; their origin remains unclear. We suggest that magnetic spiral arms can be naturally generated in the interarm regions because the galactic fountain flow or wind is likely to be weaker there than in the arms. Galactic outflows lead to two countervailing effects: removal of small-scale magnetic helicity, which helps to avert catastrophic quenching of the dynamo, and advection of the large-scale magnetic field, which suppresses dynamo action. For realistic galactic parameters, the net consequence of outflows being stronger in the gaseous arms is higher saturation large-scale field strengths in the interarm regions as compared to in the arms. By incorporating rather realistic models of spiral structure and evolution into our dynamo models, an interlaced pattern of magnetic and gaseous arms can be produced.
The Weng'an biota and the Ediacaran radiation of multicellular eukaryotes
Authors: Xiao Shuhai , Muscente A. D. , Chen Lei , Zhou Chuanming , Schiffbauer James D. , Wood Andrew D. , Polys Nicholas F. , Yuan Xunlai 
Published: October 2014

AbstractThe rise of multicellularity represents a major evolutionary transition and it occurred independently in multiple eukaryote clades. Although simple multicellular organisms may have evolved in the Mesoproterozoic Era or even earlier, complex multicellular eukaryotes began to diversify only in the Ediacaran Period, just before the Cambrian explosion. Thus, the Ediacaran fossil record can provide key paleontological evidence about the early radiation of multicellular eukaryotes that ultimately culminated in the Cambrian explosion. The Ediacaran Weng'an biota in South China hosts exceptionally preserved eukaryote fossils, including various acanthomorphic acritarchs, pseudoparenchymatous thalli, tubular microfossils, and spheroidal fossils such as Megasphaera, Helicoforamina, Spiralicellula, and Caveasphaera. Many of these fossils have been interpreted as multicellular eukaryotes, although alternative interpretations have also been proposed. In this review, we critically examine these various interpretations, focusing particularly on Megasphaera, which has been variously interpreted as a sulfur-oxidizing bacterium, a unicellular protist, a mesomycetozoean-like holozoan, a volvocine green alga, a stem-group animal, or a crown-group animal. We conclude that Megasphaera is a multicellular eukaryote with evidence for cell-to-cell adhesion, a flexible membrane unconstrained by a rigid cell wall, spatial cellular differentiation, germ–soma separation, and programmed cell death. These features are inconsistent with the bacterium, unicellular protist, and mesomycetozoean-like holozoan interpretations. Thus, the surviving hypotheses, particularly the stem-group animal and algal interpretations, should be further tested with additional evidence. The Weng'an biota also hosts cellularly differentiated pseudoparenchymatous thalli with specialized reproductive structures indicative of an affinity with florideophyte red algae. The other Weng'an fossils reviewed here may also be multicellular eukaryotes, although direct cellular evidence is lacking in some and phylogenetic affinities are poorly constrained in others. The Weng'an biota offers many research opportunities to resolve the life histories and phylogenetic diversity of early multicellular eukaryotes and to illuminate the evolutionary prelude to the Cambrian explosion.
Recent experimental progress of fractional quantum Hall effect: 5/2 filling state and graphene
Authors: Lin Xi , Du Ruirui , Xie Xincheng 
Published: October 2014

Abstract
The phenomenon of fractional quantum Hall effect (FQHE) was first experimentally observed 33 years ago. FQHE involves strong Coulomb interactions and correlations among the electrons, which leads to quasiparticles with fractional elementary charge. Three decades later, the field of FQHE is still active with new discoveries and new technical developments. A significant portion of attention in FQHE has been dedicated to filling factor 5/2 state, for its unusual even denominator and possible application in topological quantum computation. Traditionally, FQHE has been observed in high-mobility GaAs heterostructure, but new materials such as graphene also open up a new area for FQHE. This review focuses on recent progress of FQHE at 5/2 state and FQHE in graphene.
The Gentio-Oligosaccharide Gentiobiose Functions in the Modulation of Bud Dormancy in the Herbaceous PerennialGentiana
Authors: Takahashi Hideyuki , Imamura Tomohiro , Konno Naotake , Takeda Takumi , Fujita Kohei , Konishi Teruko , Nishihara Masahiro , Uchimiya Hirofumi 
Published: October 2014

AbstractBud dormancy is an adaptive strategy that perennials use to survive unfavorable conditions. Gentians (Gentiana), popular alpine flowers and ornamentals, produce overwintering buds (OWBs) that can persist through the winter, but the mechanisms regulating dormancy are currently unclear. In this study, we conducted targeted metabolome analysis to obtain clues about the metabolic mechanisms involved in regulating OWB dormancy. Multivariate analysis of metabolite profiles revealed metabolite patterns characteristic of dormant states. The concentrations of gentiobiose [β-d-Glcp-(1→6)-d-Glc] and gentianose [β-d-Glcp-(1→6)-d-Glc-(1→2)-d-Fru] significantly varied depending on the stage of OWB dormancy, and the gentiobiose concentration increased prior to budbreak. Both activation of invertase and inactivation of β-glucosidase resulted in gentiobiose accumulation in ecodormant OWBs, suggesting that gentiobiose is seldom used as an energy source but is involved in signaling pathways. Furthermore, treatment with exogenous gentiobiose induced budbreak in OWBs cultured in vitro, with increased concentrations of sulfur-containing amino acids, GSH, and ascorbate (AsA), as well as increased expression levels of the corresponding genes. Inhibition of GSH synthesis suppressed gentiobiose-induced budbreak accompanied by decreases in GSH and AsA concentrations and redox status. These results indicate that gentiobiose, a rare disaccharide, acts as a signal for dormancy release of gentian OWBs through the AsA-GSH cycle.
Interaction of morphology, thermal physiology and burrowing performance during the evolution of fossoriality in Gymnophthalmini lizards
Authors: Camacho Agustín , Pavão Rodrigo , Moreira Camila Nascimento , Pinto Ana Carolina B. C. Fonseca , Navas Carlos A. , Rodrigues Miguel Trefaut 
Published: October 2014

SummaryThe evolution of fossoriality in Squamata often leads to a phenotypic syndrome involving snake‐like body form, relatively low preferred temperature (TP) and low critical maximum temperatures (CTmax). However, how traits interacted among them and with the environment during the evolution of such syndrome remains poorly understood.We studied this process in ten species of gymnophthalmid lizards from the Brazilian Caatinga representing one full transition from typical lacertoid species to fossorial snake‐like (FSL) ones. We tested whether different morphotypes exhibited different burrowing performances in response to heat, and also differentTPand CTmax. Then, we estimated how changes in burrowing performance would relate to thermoregulation costs in terms of the number of daily hours for which preferred temperatures are available and of risk of overheating.Fossorial snake‐like species burrowed deeper, exhibited lowerTPbut kept very high CTmax, comparable to lacertoid species. A better burrowing performance and lowerTPallowed increasing the daily amount of time during whichTPwas accessible within the soil of the study region. In addition, temperatures above CTmaxof the studied species were present down to 5 cm deep, suggesting that just burrowing does not protect against exposure to extreme temperatures in species that are surface‐active during the day (all lacertoids and some FSL). Nonetheless, FSL species active at cool hours of the day exhibited lower CTmaxthan diurnal and syntopic, lacertoid and FSL species.Based on our data and previous literature, we propose a sequential explanation for the acquisition of the fossorial syndrome in Squamata.
Maternal effects and population regulation: maternal density‐induced reproduction suppression impairs offspring capacity in response to immediate environment in root voles Microtus oeconomus
Authors: Bian Jiang‐Hui , Du Shou‐Yang , Wu Yan , Cao Yi‐Fan , Nie Xu‐Heng , He Hui , You Zhi‐Bing 
Published: October 2014

Summary

The hypothesis that maternal effects act as an adaptive bridge in translating maternal environments into offspring phenotypes, and thereby affecting population dynamics has not been studied in the well‐controlled fields.

In this study, the effects of maternal population density on offspring stress axis, reproduction and population dynamics were studied in root voles (Microtus oeconomus). Parental enclosures for breeding offspring were established by introducing six adults per sex into each of 4 (low density) and 30 adults per sex into each of another 4 (high density) enclosures. Live‐trapping started 2 weeks after. Offspring captured at age of 20–30 days were removed to the laboratory, housed under laboratory conditions until puberty, and subsequently used to establish offspring populations in these same enclosures, after parental populations had been removed. [Correction added on 8 January 2015 after first online publication: ‘10–20 days’ has been changed to ‘20–30 days.’] Offspring from each of the two parental sources were assigned into four enclosures with two for each of the two density treatments used in establishing parental populations (referred to as LL and LH for maternally unstressed offspring, assigned in low and highdensity, and HL and HH for maternally stressed offspring, assigned in low and high density). Faecal corticosterone metabolites (FCM) levels, offspring reproduction traits and population dynamics were tested following repeated live‐trapping over two seasons.

Differential fluctuations in population size were observed between maternally density‐stressed and density‐unstressed offspring. Populations in LL and LH groups changed significantly in responding to initial density and reached the similar levels at beginning of the second trapping season. Populations in HL and HH groups, however, were remained relatively steady, and in HL group, the low population size was sustained until end of experiment. Maternal density stress was associated with FCM elevations, reproduction suppression and body mass decrease at sexual maturity in offspring. The FCM elevations and reproduction suppression were independent of offspring population density and correlated with decreased offspring quality.

These findings indicate that intrinsic state alterations induced by maternal stress impair offspring capacity in response to immediate environment, and these alterations are likely mediated by maternal stress system. The maladaptive reproduction suppression seen in HL group suggests intrinsic population density as one of ecological factors generating delayed density‐dependent effects.
Fungal symbiont effects on dune plant diversity depend on precipitation
Authors: Rudgers Jennifer A. , Bell‐Dereske Lukas , Crawford Kerri M. , Emery Sarah M. 
Published: October 2014

Summary

Historically, mutualisms have been considered to be less important than antagonisms in affecting the composition of ecological communities. In plant communities, beneficial microbes may feature as keystone mutualists in structuring community composition. Understanding the direction and magnitude of mutualist effects at the community scale may be critical for making accurate predictions on plant responses to climate change, particularly for mutualists that ameliorate climate‐induced stressors. Such mitigation could shift outcomes between mutualist‐enhanced species diversity and mutualist‐reduced diversity, depending on whether a mutualist accelerates habitat modification or competitive exclusion by its partner species.

Here, we tested the relative importance and interactive effects of altered precipitation and symbiosis between an epichloid fungal endophyte and a dominant grass species for dune plant communities along the Great Lakes, USA. In 2010, we imposed field manipulations of endophyte presence in the foundation dune grass Ammophila breviligulata in combination with rainout shelters and rainfall additions. We monitored natural rates of colonization by new plant individuals over 3 years.

Under the current precipitation regime, endophyte symbiosis in A. breviligulata reduced colonizing plant diversity, species richness and evenness. This effect depended on the amount of precipitation, with the symbiosis having weaker effects on plant diversity under both augmented and reduced rainfall treatments.

Despite the overall negative effect of endophyte symbiosis on plant diversity, plant responses to the endophyte were species specific. A federally threatened forb, Cirsium pitcheri, increased in abundance when the symbiosis was present, regardless of precipitation regime. Endophyte symbiosis in A. breviligulata caused minor reductions in the abundance of other grass species; however, augmented precipitation benefited other grasses.

Synthesis. We show that microbial mutualisms can have strong effects on community structure in a native ecosystem and that the amount of precipitation has the potential to alter how these keystone species interactions affect community composition. Predictions on future plant community structure, for both restored and native dunes, can be improved by accounting for the presence of fungal symbionts in the foundation plant species.
Salivary interleukin‐17 and tumor necrosis factor‐α in relation to periodontitis and glycemic status in type 2 diabetes mellitus
Authors: Gürsoy Ulvi Kahraman , Yildiz Çiftlikli Sinem , Könönen Eija , Gürsoy Mervi , Doğan Başak 
Published: October 2014

AbstractBackgroundPoorly‐controlled glycemic status in type 2 diabetes mellitus (T2DM) is suggested to play a role in the periodontal inflammatory process by aggregating the local cytokine response. Our objectives were to profile salivary interleukin (IL)‐17 and tumor necrosis factor (TNF)‐α levels in subjects with T2DM and to examine their relevance for the periodontal health status and glycemic control levels.MethodsUnstimulated whole saliva samples, together with full‐mouth periodontal recordings (plaque index [PI], bleeding on probing [BOP %], gingival index [GI], probing pocket depth [PPD], and clinical attachment level [CAL]), were collected from 123 subjects with T2DM. Additionally, demographic and general health parameters, including fasting blood glucose, glycated hemoglobin (HbA1c), were collected. Salivary IL‐17 and TNF‐α concentrations were analyzed using the Luminex®‐xMAP™ technique.ResultsSubjects with poorly‐controlled T2DM (HbA1c ≥ 7) had elevated serum triglyceride (P < 0.001) concentration as well as elevated scores of BOP % (P = 0.014), PI (P = 0.048), GI (P = 0.033), and CAL (P = 0.003) in comparison to those of well‐controlled T2DM (HbA1c < 7). When the subjects with detectable salivary IL‐17 were categorized in tertiles, the scores of PPD and BOP%, and salivary TNF‐α concentrations were significantly elevated in the highest (P = 0.007, P = 0.002 and P < 0.001, respectively) and middle (P = 0.052, P = 0.022, and P = 0.003, respectively) tertiles compared to subjects with non‐detectable salivary IL‐17. The adjusted association between PPD measurements and salivary IL‐17 concentrations was significant (P = 0.008).ConclusionsPoorly‐controlled glycemic status relates to the severity of periodontal disease in T2DM. The association between PPD and IL‐17 in saliva, however, is independent from the effect of glycemic status.
White coat effect and masked uncontrolled hypertension in treated hypertensive‐diabetic patients: Prevalence and target organ damage
Authors: Leiria Liana F. , Severo Mateus D. , Ledur Priscila S. , Becker Alexandre D. , Aguiar Fernanda M. , Massierer Daniela , Freitas Valéria C. , Schaan Beatriz D. , Gus Miguel 
Published: October 2014

AbstractBackgroundThe association between hypertensive phenotypes of controlled hypertension (CH), white‐coat effect (WCE), masked uncontrolled hypertension (MUH) and sustained hypertension (SH) with target organ damage have not been clearly established in diabetic hypertensive treated patients. The present study aims to evaluate the prevalence of the four phenotypes considering the current cut‐off points for office and 24 h‐ambulatory blood pressure monitoring (ABPM) and the association with left ventricle hypertrophy (LVH), diastolic function and nephropathy.MethodsCross‐sectional study with 304 patients on anti‐hypertensive treatment aged 57.6 ± 6.1 years, who were submitted to ABPM and echocardiography. They were classified into CH (normal office BP and ABPM), WCE (high office BP and normal ABPM), MUH (normal office BP and high ABPM), and SH (high office BP and ABPM).ResultsMedian HbA1c and diabetes duration were 7.9% (6.8–9.2), and 10 years (5–16), respectively. Prevalences of CH, WCE, MUH and SH were 27.3%, 17.1%, 18.8%, and 36.8%. MUH prevalence was higher than previously described. There was a significant increasing trend across the four groups in variables related to LVH (P < 0.001 for trend). There was not a clear “dose‐response” relationship of the four hypertensive phenotypes with nephropathy and diastolic function.ConclusionThe use of ABPM beyond the traditional cardiovascular risk stratification tools has limitations, but is still useful in high‐risk patients. Longitudinal studies could better evaluate the role of the use of ABPM in this scenario. Cut‐off points for normality of office and ABPM influence the prevalences of WCH and MUH.