bluuebunny/crossref_metadata_2025_split huggingface dataset:
The membranes of Gram-negative bacteria: progress in molecular modelling and simulation
Authors: Khalid Syma , Berglund Nils A. , Holdbrook Daniel A. , Leung Yuk M. , Parkin Jamie 
Published: August 2015

Molecular modelling and simulations have been employed to study the membranes of Gram-negative bacteria for over 20 years. Proteins native to these membranes, as well as antimicrobial peptides and drug molecules have been studied using molecular dynamics simulations in simple models of membranes, usually only comprising one lipid species. Thus, traditionally, the simulations have reflected the majority of in vitro membrane experimental setups, enabling observations from the latter to be rationalized at the molecular level.
In the last few years, the sophistication and complexity of membrane models have improved considerably, such that the heterogeneity of the lipid and protein composition of the membranes can now be considered both at the atomistic and coarse-grain levels of granularity. Importantly this means relevant biology is now being retained in the models, thereby linking the in silico and in vivo scenarios. We discuss recent progress in simulations of proteins in simple lipid bilayers, more complex membrane models and finally describe some efforts to overcome timescale limitations of atomistic molecular dynamics simulations of bacterial membranes.
How many lives does CLIMP-63 have?
Authors: Sandoz Patrick A. , van der Goot F. Gisou 
Published: August 2015

In 1995, in the Biochemical Society Transactions, Mundy published the first review on CLIMP-63 (cytoskeleton-linking membrane protein 63) or CKPA4 (cytoskeleton-associated protein 4), initially just p63 [1]. Here we review the following 20 years of research on this still mysterious protein. CLIMP-63 is a type II transmembrane protein, the cytosolic domain of which has the capacity to bind microtubules whereas the luminal domain can form homo-oligomeric complexes, not only with neighbouring molecules but also, in trans, with CLIMP-63 molecules on the other side of the endoplasmic reticulum (ER) lumen, thus promoting the formation of ER sheets. CLIMP-63 however also appears to have a life at the cell surface where it acts as a ligand-activated receptor. The still rudimentary information of how CLIMP-63 fulfills these different roles, what these are exactly and how post-translational modifications control them, will be discussed.
Sustained NRF2 activation in hereditary leiomyomatosis and renal cell cancer (HLRCC) and in hereditary tyrosinemia type 1 (HT1)
Authors: Sandhu Ivraj Singh , Maksim Nicholas James , Amouzougan Eva Alice , Gallion Bryce Wilson , Raviele Anthony L.J. , Ooi Aikseng 
Published: August 2015

The nuclear erythroid 2-like 2 transcription factor (NRF2), is a major regulator of cellular redox balance. Although NRF2 activation is generally regarded as beneficial to human health, recent studies have identified that sustained NRF2 activation is over-represented in many cancers. This raises the question regarding the role of NRF2 activation in the development and progression of those cancers. This review focuses on the mechanisms and the effects of NRF2 activation in two hereditary cancer predisposition syndromes: hereditary leiomyomatosis and renal cell cancer (HLRCC) and hereditary tyrosinemia type 1 (HT1). Because the cancer initiating mutations in these hereditary syndromes are well defined, they offer a unique opportunity to explore the roles of NRF2 activation in the early stages of carcinogenesis. Over the years, a variety of approaches have been utilized to study the biology of HLRCC and HT1. In HLRCC, in vitro studies have demonstrated the importance of NRF2 activation in sustaining cancer cell proliferation. In the mouse model of HT1 however, NRF2 activation seems to protect cells from malignant transformation. In both HT1 and HLRCC, NRF2 activation promotes the clearance of electrophilic metabolites, enabling cells to survive cancer-initiating mutations. Biological insights gained from the hereditary syndromes’ studies may shed light on to the roles of NRF2 activation in sporadic tumours.
Results of a large-scale randomized behavior change intervention on road safety in Kenya
Authors: Habyarimana James , Jack William 
Published: August 2015

Significance
Road accidents kill 1.3 million people each year, most in the developing world. Evocative messages inside Kenyan matatus, or mini-buses, that promote passenger agency and legitimize complaints against dangerous driving are found to reduce average maximum speeds and average moving speeds by 1–2 km/h and insurance claims by between one-quarter and one-third. The cost-effectiveness of the most impactful stickers is between $10 and $45 per disability-adjusted life-year saved.
Antibodies targeting human IL1RAP (IL1R3) show therapeutic effects in xenograft models of acute myeloid leukemia
Authors: Ågerstam Helena , Karlsson Christine , Hansen Nils , Sandén Carl , Askmyr Maria , von Palffy Sofia , Högberg Carl , Rissler Marianne , Wunderlich Mark , Juliusson Gunnar , Richter Johan , Sjöström Kjell , Bhatia Ravi , Mulloy James C. , Järås Marcus , Fioretos Thoas 
Published: August 2015

SignificanceAcute myeloid leukemia (AML) is a hematologic malignancy with poor survival. Current treatment with chemotherapy does not target the leukemic cells specifically and is associated with severe side effects. Here we demonstrate that antibodies directed at the cell surface molecule IL-1 receptor accessory protein (IL1RAP), expressed on immature AML cells, show strong antileukemic effects in mice transplanted with human AML cells and that the mechanism behind the cell killing is through recruitment of effector cells. Using antibodies against IL1RAP also capable of blocking IL-1 signaling, we show that the proliferation of human AML cells can be inhibited, providing a second mode of action of IL1RAP antibodies. These results provide critical evidence in support of a rapid clinical development of an antibody-based anti-IL1RAP therapy in AML.
Systems biology definition of the core proteome of metabolism and expression is consistent with high-throughput data
Authors: Yang Laurence , Tan Justin , O’Brien Edward J. , Monk Jonathan M. , Kim Donghyuk , Li Howard J. , Charusanti Pep , Ebrahim Ali , Lloyd Colton J. , Yurkovich James T. , Du Bin , Dräger Andreas , Thomas Alex , Sun Yuekai , Saunders Michael A. , Palsson Bernhard O. 
Published: August 2015

Significance
Defining a core functional proteome supporting the living process has importance for both developing fundamental understanding of cell functions and for synthetic biology applications. Comparative genomics has been the primary approach to achieve such a definition. Here, we use genome-scale models to define a core proteome that computationally supports basic cellular function. This core proteome for metabolism and protein expression, defined through systems biology methods, is validated and characterized by using multiple disparate data types.
Quantifying the impact of weak, strong, and super ties in scientific careers
Authors: Petersen Alexander Michael 
Published: August 2015

Significance
A scientist will encounter many potential collaborators throughout his/her career. As such, the choice to start or terminate a collaboration can be an important strategic consideration with long-term implications. While previous studies have focused primarily on aggregate cross-sectional collaboration patterns, here we analyze the collaboration network from a researcher’s local perspective along his/her career. Our longitudinal approach reveals that scientific collaboration is characterized by a high turnover rate juxtaposed with surprisingly frequent “life partners.” We show that these extremely strong collaborations have a significant positive impact on productivity and citations—the apostle effect—representing the advantage of “super” social ties characterized by trust, conviction, and commitment.
The amino acid sensor GCN2 inhibits inflammatory responses to apoptotic cells promoting tolerance and suppressing systemic autoimmunity
Authors: Ravishankar Buvana , Liu Haiyun , Shinde Rahul , Chaudhary Kapil , Xiao Wei , Bradley Jillian , Koritzinsky Marianne , Madaio Michael P. , McGaha Tracy L. 
Published: August 2015

Significance
Metabolic stress potently modifies immunity. Recently our laboratory identified the stress kinase GCN2 as a key modulator of macrophage responses to toll-like receptor ligands; however, the role of myeloid GCN2 signals in sterile inflammation and homeostatic tolerance is not known. In this study, we tested the requirement of GCN2 for tolerance to apoptotic cells and prevention of autoimmunity in a model of lupus. Our results show that GCN2 in myeloid cells is a critical effector of apoptotic cell-driven tolerance required for regulatory cytokine production and prevention of inflammatory immunity. Moreover, the data indicate that targeting GCN2 is an effective approach to preventing autoimmunity, providing a rationale for developing tools to manipulate GCN2 function in inflammatory immune disease.
Continuous evolutionary change in Plio-Pleistocene mammals of eastern Africa
Authors: Bibi Faysal , Kiessling Wolfgang 
Published: August 2015

Significance
Many have argued that major developments in mammalian (including human) evolution were timed with large and sudden changes to Earth’s climate. Our new analyses of the eastern African Plio-Pleistocene mammalian fossil record indicate that most species originations and extinctions took place continuously and gradually. This means that evolution was not clustered in short intervals, nor were sudden global climatic changes the main cause of species extinction in the past. Global climate may have influenced longer-term (million year) evolutionary trends, but local environmental changes and species interactions were more important at shorter (100,000 y) time scales.
Adaptive aneuploidy protects against thiol peroxidase deficiency by increasing respiration via key mitochondrial proteins
Authors: Kaya Alaattin , Gerashchenko Maxim V. , Seim Inge , Labarre Jean , Toledano Michel B. , Gladyshev Vadim N. 
Published: August 2015

Significance
Aneuploidy, a condition of abnormal chromosomal content, can support adaptive mechanisms in response to environmental cues but comes at the expense of decreased proliferation and dysfunction of cellular processes. Here we show that the gain of an extra copy of chromosome XI in yeast is an adaptive mechanism to deal with oxidative stress under conditions of antioxidant deficiency. We narrowed down the effect of adaptive aneuploidy to two genes on chromosome XI, which supported increased mitochondrial abundance and respiration, which in turn provided reducing equivalents for hydroperoxide removal. Forced expression of these genes eliminated aneuploidy, improved cell growth, and was sufficient for protection against oxidative stress. Thus, aneuploidy can adaptively reprogram cellular metabolism, protecting against oxidative stress by upregulating respiration.
Geometry and mechanics of two-dimensional defects in amorphous materials
Authors: Moshe Michael , Levin Ido , Aharoni Hillel , Kupferman Raz , Sharon Eran 
Published: August 2015

Significance
Modeling defects, or localized strain carriers, are a central challenge in the formulation of elasto-plastic theory of amorphous solids. Whereas in crystalline solids defects are identified as local deviations from the crystal order, it is not clear how, or even if, equivalent intrinsic entities can be defined in amorphous solids. This work presents a new way of defining and describing localized intrinsic geometrical defects in amorphous solids and for computing the stresses within defected bodies. The methods and results that are presented here can be integrated into phenomenological theories of plasticity and can be applied to biomechanical problems that involve strain localization.
Thermophilization of adult and juvenile tree communities in the northern tropical Andes
Authors: Duque Alvaro , Stevenson Pablo R. , Feeley Kenneth J. 
Published: August 2015

SignificanceUnderstanding how species respond to climate change is crucial to the development of effective conservation strategies. We found directional and systematic changes in the composition of both adult and juvenile tree species in tropical north Andean forests at rates consistent with concurrent temperature increases, supporting the hypothesis of upward species migrations resulting from global warming. Our results indicate that compositional shifts occur primarily via range retractions. This suggests elevated risk for species extinctions and local biodiversity loss with ongoing warming. Other environmental filters, such as species-soil adaptations, as well as anthropogenic disturbances (e.g., habitat loss and hunting) may limit future species migrations and decrease the ability of forest communities and their constituent species to respond to climate change.
Comanaging fresh produce for nature conservation and food safety
Authors: Karp Daniel S. , Gennet Sasha , Kilonzo Christopher , Partyka Melissa , Chaumont Nicolas , Atwill Edward R. , Kremen Claire 
Published: August 2015

Significance
Fresh produce has become the primary cause of foodborne illness in the United States. A widespread concern that wildlife vector foodborne pathogens onto fresh produce fields has led to strong pressure on farmers to clear noncrop vegetation surrounding their farm fields. We combined three large datasets to demonstrate that pathogen prevalence in fresh produce is rapidly increasing, that pathogens are more common on farms closer to land suitable for livestock grazing, and that vegetation clearing is associated with increased pathogen prevalence over time. These findings contradict widespread food safety reforms that champion vegetation clearing as a pathogen mitigation strategy. More generally, our work indicates that achieving food safety and nature conservation goals in produce-growing landscapes is possible.
Stationary States and Modulational Instability of Coupled Two-Component Bose–Einstein Condensates in a Ring Trap*
Authors: Deng Hai-Ming , Zhong Hong-Hua , Huang Jia-Hao , Dai Hui , Yao Min , Huang Xiao-Yi 
Published: August 2015

Abstract
We investigate modulational instability (MI) of a coupled two-component Bose–Einstein condensates in a rotating ring trap. The excitation spectrum and the MI condition of the system are presented analytically. We find that the coupling between the two components strongly modifies the MI condition, and the MI condition is phase-dependent. Furthermore, we discuss the effect of MI on both density excitation and spin excitation. If the inter- and intra-component interaction strengths are all equal, the MI causes density excitation but not spin excitation, and if the inter- and intra-component interaction strengths are different, the MI causes both density excitation and spin excitation. Our results provide a promising approach for controlling the stability and excitation of a rotating two-component Bose–Einstein condensates by modulating its coupling strength and interaction strength.
The Effect of Spin-Orbit Coupling and Spin-Spin Coupling of Compact Binaries on Chaos*
Authors: Wang Hong , Huang Guo-Qing 
Published: August 2015

Abstract
There are spin-orbit interaction and spin-spin interaction in a generic post-Newtonian Lagrangian formulation of comparable mass spinning compact binaries. The spin-orbit coupling or the spin-spin coupling plays a quite important role in changing the evolution of the system and may sometime cause chaotic behavior. How do the two types of couplings exert together any influences on chaos in this formulation? To answer it, we simply take the Lagrangian formulation of a special binary system, including the Newtonian term and the leading-order spin-orbit and spin-spin couplings. The key to this question can be found from a Hamiltonian formulation that is completely identical to the Lagrangian formulation. If the Lagrangian does not include the spin-spin coupling, its equivalent Hamiltonian has an additional term (i.e. the next-order spin-spin coupling) as well as those terms of the Lagrangian. The spin-spin coupling rather than the spin-orbit coupling makes the Hamiltonian typically nonintegrable and probably chaotic when two objects spin. When the leading-order spin-spin coupling is also added to the Lagrangian, it still appears in the Hamiltonian. In this sense, the total Hamiltonian contains the leading-order spin-spin coupling and the next-order spin-spin coupling, which have different signs. Therefore, the chaos resulting from the spin-spin interaction in the Legrangian formulations is somewhat weakened by the spin-orbit coupling.
Critical Behaviors and Universality Classes of Percolation Phase Transitions on Two-Dimensional Square Lattice*
Authors: Zhu Yong , Yang Zi-Qing , Zhang Xin , Chen Xiao-Song 
Published: August 2015

Abstract
We have investigated both site and bond percolation on two-dimensional lattice under the random rule and the product rule respectively. With the random rule, sites or bonds are added randomly into the lattice. From two candidates picked randomly, the site or bond with the smaller size product of two connected clusters is added when the product rule is taken. Not only the size of the largest cluster but also its size jump are studied to characterize the universality class of percolation. The finite-size scaling forms of giant cluster size and size jump are proposed and used to determine the critical exponents of percolation from Monte Carlo data. It is found that the critical exponents of both size and size jump in random site percolation are equal to that in random bond percolation. With the random rule, site and bond percolation belong to the same universality class. We obtain the critical exponents of the site percolation under the product rule, which are different from that of both random percolation and the bond percolation under the product rule. The universality class of site percolation differs different from that of bond percolation when the product rule is used.
Vizardous: interactive analysis of microbial populations with single cell resolution
Authors: Helfrich Stefan , Azzouzi Charaf E. , Probst Christopher , Seiffarth Johannes , Grünberger Alexander , Wiechert Wolfgang , Kohlheyer Dietrich , Nöh Katharina 
Published: August 2015

Abstract
Motivation: Single cell time-lapse microscopy is a powerful method for investigating heterogeneous cell behavior. Advances in microfluidic lab-on-a-chip technologies and live-cell imaging render the parallel observation of the development of individual cells in hundreds of populations possible. While image analysis tools are available for cell detection and tracking, biologists are still confronted with the challenge of exploring and evaluating this data.
Results: We present the software tool Vizardous that assists scientists with explorative analysis and interpretation tasks of single cell data in an interactive, configurable and visual way. With Vizardous, lineage tree drawings can be augmented with various, time-resolved cellular characteristics. Associated statistical moments bridge the gap between single cell and the population-average level.
Availability and implementation: The software, including documentation and examples, is available as executable Java archive as well as in source form at https://github.com/modsim/vizardous.
Contact: k.noeh@fz-juelich.de
Supplementary information: Supplementary data are available at Bioinformatics online.
Neuropathic Allodynia Involves Spinal Neurexin-1β-dependent Neuroligin-1/Postsynaptic Density-95/NR2B Cascade in Rats
Authors: Lin Tzer-Bin , Lai Cheng-Yuan , Hsieh Ming-Chun , Jiang Jian-Lin , Cheng Jen-Kun , Chau Yat-Pang , Ruan Ting , Chen Gin-Den , Peng Hsien-Yu 
Published: August 2015

AbstractAbstract
It was shown that the association of N-methyl-d-aspartate receptor NR2B subunits and postsynaptic density-95 scaffolding protein was enhanced in spinal cord dorsal horn neurons after nerve ligation in rats. The disruption of neurexin-1β–neuroligin-1 interaction reduced allodynia and NR2B–postsynaptic density-95 interactions in nerveligated rats.

Background:
Neuroligin-1 (NL1) forms a complex with the presynaptic neurexin-1β (Nrx1b), regulating clustering of N-methyl-d-aspartate receptors with postsynaptic density-95 (PSD-95) to underlie learning-/memory-associated plasticity. Pain-related spinal neuroplasticity shares several common features with learning-/memory-associated plasticity. The authors thereby investigated the potential involvement of NL1-related mechanism in spinal nerve ligation (SNL)–associated allodynia.

Methods:
In 626 adult male Sprague–Dawley rats, the withdrawal threshold and NL1, PSD-95, phosphorylated NR2B (pNR2B) expressions, interactions, and locations in dorsal horn (L4 to L5) were compared between the sham operation and SNL groups. A recombinant Nrx1b Fc chimera (Nrx1b Fc, 10 μg, 10 μl, i.t., bolus), antisense small-interfering RNA targeting to NL1 (10 μg, 10 μl, i.t., daily for 4 days), or NR2B antagonist (Ro 25-6981; 1 μM, 10 μl, i.t., bolus) were administered to SNL animals to elucidate possible cascades involved.

Results:
SNL-induced allodynia failed to affect NL1 or PSD-95 expression. However, pNR2B expression (mean ± SD from 13.1 ± 2.87 to 23.1 ± 2.52, n = 6) and coexpression of NL1–PSD-95, pNR2B–PSD-95, and NL1-total NR2B were enhanced by SNL (from 10.7 ± 2.27 to 22.2 ± 3.94, 11.5 ± 2.15 to 23.8 ± 3.32, and 8.9 ± 1.83 to 14.9 ± 2.27 at day 7, n = 6). Furthermore, neuron-localized pNR2B PSD-95–pNR2B double-labeled and NL1/PSD-95/pNR2B triple-labeled immunofluorescence in the ipsilateral dorsal horn was all prevented by Nrx1b Fc and NL1-targeted small-interfering RNA designed to block and prevent NL1 expression. Without affecting NL1–PSD-95 coupling, Ro 25-6981 decreased the SNL-induced PSD-95–pNR2B coprecipitation (from 18.7 ± 1.80 to 14.7 ± 2.36 at day 7, n = 6).

Conclusion:
SNL-induced allodynia, which is mediated by the spinal NL1/PSD-95/pNR2B cascade, can be prevented by blockade of transsynaptic Nrx1b–NL1 interactions.
Atp6v1b2Plays Important Roles in the Early Development of Hearing, the Pectoral Fin, the Cardiovascular System, and the Swim Bladder of the Zebrafish, Supporting a Role for the Gene in Syndromic Hearing Loss
Authors: Yuan Yongyi , Gao Xue , Xin Feng , Dai Pu 
Published: August 2015

AbstractBackgroundTheATP6V1B2gene plays a critical role in the auditory system, and a mutation in this gene is one genetic cause of DDOD syndrome (Dominant deafness-onychodystrophy syndrome, MIM 124480) and ZLS (Zimmermann-Laband syndrome, MIM 135500). However, whether and howATP6V1B2is involved in the development of other organs remains unknown. In the present study, we explored the effect ofatp6v1b2knockdown on early zebrafish development and verified that this gene plays a role in syndromic hearing loss.MethodsThree morpholinos (two splice-blocking, one translation-blocking) and theatp6v1b2c.1516 C>T plasmid were used to knockdown or overexpress atp6v1b2 in zebrafish after microinjection of fertilised embryos. Control andatp6v1b2embryo morphants were evaluated 6 days post-fertilisation in terms of motility, apoptosis, pectoral fin development, and hair cell number.ResultsAtp6v1b2-knockdown zebrafish exhibited decreased body length, pericardial oedema, hair cell loss, a non-inflated swim bladder, and shorter pectoral fins; the first three phenotypes were also evident in fish overexpressing the gene.ConclusionsAtp6v1b2plays important roles in the development of hearing, the pectoral fin, the cardiovascular system, and the swim bladder, thereby supporting a role for this gene in syndromic hearing loss.