bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flourishing ocean drives the end-Permian marine mass extinction
Authors: Schobben Martin , Stebbins Alan , Ghaderi Abbas , Strauss Harald , Korn Dieter , Korte Christoph 
Published: August 2015

Significance
This study provides geochemical evidence that links some of the most important finds associated with the end-Permian mass extinction, including climate warming, enhanced weathering, increased primary productivity, and widespread marine anoxia under a common denominator: the linked biogeochemical sulfur and carbon cycles. Lethal marine conditions are likely the result of climate feedback mechanisms acting to increase nutrient input to the ocean, thereby stimulating global organic carbon production. With future projected climate change in mind, such climate feedback mechanisms could induce widespread eutrophication and expansion of anoxic and sulfidic zones, thereby fundamentally altering marine ecosystems.
Creative template-dependent synthesis by human polymerase mu
Authors: Moon Andrea F. , Gosavi Rajendrakumar A. , Kunkel Thomas A. , Pedersen Lars C. , Bebenek Katarzyna 
Published: August 2015

Significance
Template-dependent DNA polymerases usually add nucleotides to the 3ʹ end of a primer, using the first available template-strand nucleotide as a guide. This behavior holds true for all polymerases, except one, DNA polymerase μ. When presented with 2-nt single- or double-strand gaps, polymerase μ (Pol μ) engages the substrate with the last available template-strand nucleotide closest to the 5′-phosphate on the downstream end of the gap, guiding synthesis. Crystal structures of Pol μ with a 2-nt gapped DNA substrate explain how the unpaired base is accommodated in the active site, and yield insights into the behavior of this polymerase within the context of nonhomologous end joining in DNA double-strand break repair.
Crowded growth leads to the spontaneous evolution of semistable coexistence in laboratory yeast populations
Authors: Frenkel Evgeni M. , McDonald Michael J. , Van Dyken J. David , Kosheleva Katya , Lang Gregory I. , Desai Michael M. 
Published: August 2015

SignificanceThe spontaneous emergence of stable coexistence between competing lineages in experimental evolution illustrates principles behind the creation and maintenance of biodiversity. Here, we present the first experimental observation of a general mechanism that leads to stable diversification in microbial populations despite competition for shared resources. Coexistence in our system depends on a tradeoff between growth and the ability to avoid cellular crowding. We elucidate the biophysical and genetic basis of this coexistence, and introduce a mathematical model that explains our results. Our analysis demonstrates that this coexistence can be perturbed by evolution on longer time scales, providing a unique quantitative example of how the interactions between ecological and evolutionary processes can create and destroy diversity in microbial populations.
Flow perfusion effects on three-dimensional culture and drug sensitivity of Ewing sarcoma
Authors: Santoro Marco , Lamhamedi-Cherradi Salah-Eddine , Menegaz Brian A. , Ludwig Joseph A. , Mikos Antonios G. 
Published: August 2015

Significance
Most preclinical drug screening systems fail to predict whether a given drug candidate will succeed in clinical trials due to the fact that cells are plated on culture dishes devoid of signaling cues present in vivo. Among other factors, biomechanical stimulation strongly affects tumor behavior. Toward this end, we cultured Ewing sarcoma cells on 3D scaffolds within a flow perfusion bioreactor, which provides mechanical stimulation in the form of flow-derived shear stress. Cells exposed to flow perfusion produced more insulin-like growth factor-1 (IGF-1) ligand and showed shear stress-dependent sensitivity to IGF-1 receptor targeted drugs when compared with static conditions. Collectively, this research provides an improved method to study cancer cells ex vivo and could narrow the gap between preclinical and clinical drug activity.
Switching of perpendicularly polarized nanomagnets with spin orbit torque without an external magnetic field by engineering a tilted anisotropy
Authors: You Long , Lee OukJae , Bhowmik Debanjan , Labanowski Dominic , Hong Jeongmin , Bokor Jeffrey , Salahuddin Sayeef 
Published: August 2015

Significance
When a spin orbit torque is applied to a magnet with perpendicular anisotropy, the induced spin accumulation is completely symmetric with respect to the magnetization. As a result, a deterministic switching cannot be achieved unless an external magnetic field is applied to break the symmetry. Here, we show that, by engineering a tilted anisotropy in a magnetic nanodot, the symmetry can effectively be broken and a deterministic switching of perpendicular magnetization can be achieved without needing the external magnetic field. These results are significant for the field of spintronics as the symmetry breaking provides new insight into the physics of spin orbit torque and the switching without a magnetic field could lead to significant impact in high-density storage applications.
Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment
Authors: Dou Zhen , Liu Xing , Wang Wenwen , Zhu Tongge , Wang Xinghui , Xu Leilei , Abrieu Ariane , Fu Chuanhai , Hill Donald L. , Yao Xuebiao 
Published: August 2015

Significance
The spindle assembly checkpoint (SAC) works as a surveillance mechanism to ensure accurate segregation of genetic materials during cell division. Protein kinase monopolar spindle 1 (Mps1) plays a key role in SAC, but the mechanism of Mps1 action in chromosome segregation remains elusive. In this study, we identified a previously undefined structural determinant of Mps1 named “IRK” (internal region for kinetochore localization) and demonstrated its functional importance in accurate kinetochore–microtubule attachment. Mechanistically, a dynamic hierarchical interaction between Mps1 and the nuclear division cycle 80 complex (Ndc80C) orchestrates accurate mitosis, because persistent association of inactive Mps1 with Ndc80C via the IRK perturbs correct kinetochore–microtubule attachment. Our results provide a new mechanistic insight into the spatiotemporal dynamics of Mps1 activity at the kinetochore in mitosis.
Siderocalin-mediated recognition, sensitization, and cellular uptake of actinides
Authors: Allred Benjamin E. , Rupert Peter B. , Gauny Stacey S. , An Dahlia D. , Ralston Corie Y. , Sturzbecher-Hoehne Manuel , Strong Roland K. , Abergel Rebecca J. 
Published: August 2015

Significance
The release of actinides in the environment, particularly after a nuclear power plant accident or the potential use of a radiological dispersal device, is a public health threat, as all actinides are radioactive and will trigger damage once internalized by the human body. The biological chemistry of actinide metal ions is largely unknown and new approaches to the understanding of pathways underlying contamination are needed. This work identifies a new mammalian pathway for the intracellular delivery of the radioactive toxic metal ions that are actinides, through the protein siderocalin. Spectroscopic tools, including X-ray diffraction and luminescence, provided insights on the coordination of these metal ions, which is crucial to devise new strategies for decontamination.
Direct calculation of ice homogeneous nucleation rate for a molecular model of water
Authors: Haji-Akbari Amir , Debenedetti Pablo G. 
Published: August 2015

Significance
Despite the importance of ice nucleation in a wide range of natural and technological systems, it is not trivial to predict its kinetics or unravel its mechanism experimentally. It is also challenging to study the stochastic nature of ice nucleation in computer simulations. The direct calculation of the nucleation rate for realistic molecular models of water is commonly regarded as one of the most challenging open problems in computational studies of water. By applying a novel coarse-graining modification to the forward-flux sampling technique, we perform the first direct rate calculation for TIP4P/Ice, one of the best existing molecular models of water. We also identify the molecular origin of the preference for the cubic polymorph during the homogeneous nucleation process.
In vivo imaging of axonal transport of mitochondria in the diseased and aged mammalian CNS
Authors: Takihara Yuji , Inatani Masaru , Eto Kei , Inoue Toshihiro , Kreymerman Alexander , Miyake Seiji , Ueno Shinji , Nagaya Masatoshi , Nakanishi Ayami , Iwao Keiichiro , Takamura Yoshihiro , Sakamoto Hirotaka , Satoh Keita , Kondo Mineo , Sakamoto Tatsuya , Goldberg Jeffrey L. , Nabekura Junichi , Tanihara Hidenobu 
Published: August 2015

Significance
The lack of intravital imaging of axonal transport of mitochondria in the living mammalian CNS precludes the characterization of transport dynamics in the diseased and aged mammalian CNS. Here we report minimally invasive intravital multiphoton imaging of mouse retinal ganglion cells that offers sequential time-lapse images of mitochondria transported in a single axon with submicrometer resolution. We show highly dynamic axonal transport of mitochondria in the mammalian CNS in vivo under physiological conditions and characterize disturbances of mitochondrial transport in a mouse glaucoma model and age-related changes in mitochondrial transport. Our method is useful for characterizing the dynamics of axonal transport of mitochondria and the dynamics of other submicrometer structures in the diseased and aged mammalian CNS in vivo.
RabGDIα is a negative regulator of interferon-γ–inducible GTPase-dependent cell-autonomous immunity toToxoplasma gondii
Authors: Ohshima Jun , Sasai Miwa , Liu Jianfa , Yamashita Kazuo , Ma Ji Su , Lee Youngae , Bando Hironori , Howard Jonathan C. , Ebisu Shigeyuki , Hayashi Mikako , Takeda Kiyoshi , Standley Daron M. , Frickel Eva-Maria , Yamamoto Masahiro 
Published: August 2015

SignificanceIFN-γ is a proinflammatory cytokine and stimulates induction of ∼2,000 genes, including IFN-γ–inducible GTPases, such as immunity-related GTPases (IRGs) and guanylate-binding proteins (GBPs), that are critically required for cell-autonomous host defense against the vacuolar pathogenToxoplasma gondii. Mechanisms of how recruitment of these GTPases to the vacuoles is positively regulated have been gradually elucidated. However, the negative regulation remains unknown. Here, we show that Rab GDP dissociation inhibitor α (RabGDIα) acts as a suppressor of IFN-γ–inducible GTPases, such as Gbp2 and Irga6. RabGDIα deficiency resulted in enhanced IFN-γ–mediatedT. gondiiclearance in vitro and in vivo. Furthermore, RabGDIα inhibited the act of Gbp2 and Irga6 through the lipid-binding pocket. Thus, our current study demonstrates a negative regulatory mechanism for IFN-γ–inducible GTPase-dependent cell-autonomous immunity.
Defect tolerance and the effect of structural inhomogeneity in plasmonic DNA-nanoparticle superlattices
Authors: Ross Michael B. , Ku Jessie C. , Blaber Martin G. , Mirkin Chad A. , Schatz George C. 
Published: August 2015

Significance
Materials constructed with metal nanoparticles interact strongly with light, enabling functions such as tunable color, molecular sensors, and light-based electronics. These materials, however, are often imperfect; nanoparticles vary in their size, shape, and surface morphology, which can affect the quality of their arrangement as well as their properties. We use DNA to synthesize precisely controlled crystalline arrangements of gold nanoparticles and survey how a variety of structural inhomogeneities affects their optical properties. The results reported herein identify specific metal nanoparticle-based materials whose optical properties are either sensitive or insensitive to inhomogeneity.
Hypertension Prevalence, Awareness, Treatment, and Control Following China’s Healthcare Reform
Authors: Hou Zhiyuan , Meng Qingyue , Zhang Yuting 
Published: August 2015

Abstract

BACKGROUND
In 2009, China started an impressive national healthcare system reform. One of the key components is to promote equity in access to essential healthcare services including chronic disease management. We assessed the changes in hypertension management and its equity before and after China’s healthcare reform in 2009.

METHODS
We used data from the 2008 and 2012 waves of the China Health and Retirement Longitudinal Study (CHARLS). The surveys were conducted in Zhejiang and Gansu provinces, containing 1,961 and 1,836 respondents aged 45 and older in 2008 and 2012 respectively. We measured the prevalence of hypertension, and proportions of respondents with hypertension aware of their conditions, receiving treatment and under effective control, separately for 2008 and 2012. We also reported these measures in provinces and rural/urban areas.

RESULTS
From 2008 to 2012, the age standardized prevalence of hypertension was steady at 46.2%, but hypertension management improved substantially. Among those with hypertension, the proportion of patients aware of their conditions increased from 57.8% to 69.9%, the proportion of patients receiving treatment increased from 38.1% to 56.1%, and the proportion of patients with hypertension under effective control increased from 21.7% to 36.4%. The highest improvement was found in rural areas of the underdeveloped province, which indicated that the inequity across regions declined over time.

CONCLUSIONS
Among Chinese population aged 45 and older in Zhejiang and Gansu provinces, hypertension management improved following healthcare reform. The rate of improvement was faster in rural and underdeveloped areas, possibly related to additional governmental subsidies to these areas.
Association of Endothelial and Mild Renal Dysfunction With the Severity of Left Ventricular Hypertrophy in Hypertensive Patients
Authors: Cao Cheng , Hu Jian-Xin , Dong Yi-Fei , Zhan Rui , Li Ping , Su Hai , Peng Qiang , Wu Tao , Huang Xiao , Sun Wen-Hua , Wu Qing-Hua , Cheng Xiao-Shu 
Published: August 2015

Abstract

BACKGROUND
The association between impaired renal function and increase left ventricular mass was shown to be related to increase in arterial stiffness, which indicates that vascular homeostasis and remodeling may impact the left ventricular hypertrophy (LVH) in patients with renal dysfunction.

METHODS
We measured the peripheral arterial reactive hyperemia index (RHI) and estimated glomerular filtration rate (eGFR) in 317 hypertensive patients comprising 115 normal RHI (RHI &gt; 1.67) and normal eGFR (eGFR ≥ 90ml/min per 1.73 m 2 ), 136 low RHI (RHI ≤ 1.67), 27 low eGFR (60 ≤ eGFR &lt; 90ml/min per 1.73 m 2 ) and 39 low RHI combined with low eGFR.

RESULTS
Multivariate logistic regression analysis identified lg RHI (odds ratio (OR): 0.001, 95% confidence interval (CI): 10 –6 to 0.426, P = 0.024) and lg eGFR (OR: 0.009, 95% CI: 10 –4 to 0.414, P = 0.016) as independent factors correlated with LVH respectively in hypertensive patients. Compared with normal RHI and eGFR patients, the extent of LVH in patients with either low RHI (OR: 1.224 95% CI: 0.451 to 3.327, P = 0.691) or low eGFR (OR: 0.593 95% CI: 0.070 to 5.037, P = 0.632) did not significantly increase, while it increased significantly in patients with low RHI combined with low eGFR (OR: 4.629 95% CI: 1.592 to 13.458, P = 0.005).

CONCLUSIONS
The concurrence of endothelial and mild renal dysfunction was significantly associated with the severity of LVH in hypertensive patients.
PBAP: a pipeline for file processing and quality control of pedigree data with dense genetic markers
Authors: Nato Alejandro Q. , Chapman Nicola H. , Sohi Harkirat K. , Nguyen Hiep D. , Brkanac Zoran , Wijsman Ellen M. 
Published: August 2015

Abstract
Motivation: Huge genetic datasets with dense marker panels are now common. With the availability of sequence data and recognition of importance of rare variants, smaller studies based on pedigrees are again also common. Pedigree-based samples often start with a dense marker panel, a subset of which may be used for linkage analysis to reduce computational burden and to limit linkage disequilibrium between single-nucleotide polymorphisms (SNPs). Programs attempting to select markers for linkage panels exist but lack flexibility.
Results: We developed a pedigree-based analysis pipeline (PBAP) suite of programs geared towards SNPs and sequence data. PBAP performs quality control, marker selection and file preparation. PBAP sets up files for MORGAN, which can handle analyses for small and large pedigrees, typically human, and results can be used with other programs and for downstream analyses. We evaluate and illustrate its features with two real datasets.
Availability and implementation: PBAP scripts may be downloaded from http://faculty.washington.edu/wijsman/software.shtml.
Contact: wijsman@uw.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
AlignBucket: a tool to speed up ‘all-against-all’ protein sequence alignments optimizing length constraints
Authors: Profiti Giuseppe , Fariselli Piero , Casadio Rita 
Published: August 2015

Abstract
Motivation: The next-generation sequencing era requires reliable, fast and efficient approaches for the accurate annotation of the ever-increasing number of biological sequences and their variations. Transfer of annotation upon similarity search is a standard approach. The procedure of all-against-all protein comparison is a preliminary step of different available methods that annotate sequences based on information already present in databases. Given the actual volume of sequences, methods are necessary to pre-process data to reduce the time of sequence comparison.
Results: We present an algorithm that optimizes the partition of a large volume of sequences (the whole database) into sets where sequence length values (in residues) are constrained depending on a bounded minimal and expected alignment coverage. The idea is to optimally group protein sequences according to their length, and then computing the all-against-all sequence alignments among sequences that fall in a selected length range. We describe a mathematically optimal solution and we show that our method leads to a 5-fold speed-up in real world cases.
Availability and implementation: The software is available for downloading at http://www.biocomp.unibo.it/∼giuseppe/partitioning.html.
Contact: giuseppe.profiti2@unibo.it
Supplementary information: Supplementary data are available at Bioinformatics online.
Identifying a set that contains the best dynamic treatment regimes
Authors: Ertefaie Ashkan , Wu Tianshuang , Lynch Kevin G. , Nahum-Shani Inbal 
Published: August 2015

AbstractA dynamic treatment regime (DTR) is a treatment design that seeks to accommodate patient heterogeneity in response to treatment. DTRs can be operationalized by a sequence of decision rules that map patient information to treatment options at specific decision points. The sequential, multiple assignment, randomized trial (SMART) is a trial design that was developed specifically for the purpose of obtaining data that informs the construction of good (i.e. efficacious) decision rules. One of the scientific questions motivating a SMART concerns the comparison of multiple DTRs that are embedded in the design. Typical approaches for identifying the best DTRs involve all possible comparisons between DTRs that are embedded in a SMART, at the cost of greatly reduced power to the extent that the number of embedded DTRs (EDTRs) increase. Here, we propose a method that will enable investigators to use SMART study data more efficiently to identify the set that contains the most efficacious EDTRs. Our method ensures that the true best EDTRs are included in this set with at least a given probability. Simulation results are presented to evaluate the proposed method, and the Extending Treatment Effectiveness of Naltrexone SMART study data are analyzed to illustrate its application.
Bodily Dis-ease in Contemporary French Women's Writing: Two Case Studies
Authors: Cairns Lucille 
Published: August 2015

Abstract

This article examines two twenty-first-century autobiographical accounts of the intense — and ultimately life-threatening — mental and bodily dis-ease endured by two young French women from adolescence into early adulthood. Annick Loupias's
La Tortue sur le dos
(2001) and Émilie Durand's
Ma folie ordinaire
(2006) are phenomenologically rich and visceral testimonies to their authors' experiences of anorexia nervosa, bulimia nervosa, other forms of self-harm (inter alia, self-cutting and self-burning), and even suicide attempts. I argue that, in common with the texts of many other French female writers who have approached these subjects in the last two decades, their value is not so much literary as more broadly cultural, allowing important sociopolitical and medical insights about these markedly gendered illnesses which have seen an inexorable rise in the late twentieth and early twenty-first centuries, but which are still often misunderstood, even by educated readers, and even by the healthcare professionals who attempt to treat sufferers. The article sets these texts in a material, extra-diegetic context, ascertains the aetiologies of the pathologies they inscribe, draws out some of the key insights they afford about those pathologies, and identifies some of the formal means by which these insights are conveyed.
Innocence and Childhood
Authors: Bühler-Niederberger Doris 
Published: August 2015

The notion of innocence refers to children’s simplicity, their lack of knowledge, and their purity not yet spoiled by mundane affairs. Such innocence is taken as the promise of a renewal of the world by the children. Innocence has been attributed to children and childhood by adults at all times, but content and social function of such glorifying assessments show considerable variation over time and context, and the valuation is never unanimous among contemporaries. Innocence used to be a religious notion in earlier times. With the Enlightenment and success of Rousseau’s Émile, nature becomes a new point of reference. From the 19th century onward, the idea of children’s innocence is strongly interrelated with children’s sexuality. Innocence is then emphasized to defend the assumption of an absence of sexuality in children and the demand for such absence. Innocence is not a scientific term; therefore, the numerous studies concerning processes, seminal ideas, and functions of the value assessment of children and childhood do not constitute a unified research area. Researchers deal with questions of children’s innocence often rather implicitly. They do so while analyzing the social construction and reconstruction of childhood at different times and in different historical and contemporary contexts. They do so as well in the interpretation of classic pedagogy, as innocence is a conceptual element in the writings of several pedagogues. Last but not least, we find references to notions of innocence in studies on discourses and political programs concerning children’s sexuality and in the scientific reconstruction of moral enterprises called “moral panics”: public outcries concerning improper childhoods. Put together, these studies, which are scattered over multiple research fields, support the following conclusions: (1) various value assessments of children and childhood may be found at all times, and the notion of innocence is never uncontested; (2) historical notions of innocence are complex and may as well recognize children’s agency; (3) the attribution of innocence to children is often functionalized by interest groups to support their claims and to devaluate rival or marginal groups; it may therefore be a value assessment of minor profit for the children, but of high profit for interest groups; (4) while the attribution of innocence has had a clear reference to religion and nature implicating far-reaching assumptions concerning humankind, it is almost completely narrowed down to debates on children’s sexuality and sexual endangerment in the early 21st century.