bluuebunny/crossref_metadata_2025 huggingface dataset:
Future public pensions and changing employment patterns across birth cohorts
Authors: GEYER JOHANNES , STEINER VIKTOR
Published: November 2013

We analyse the impacts of changing employment patterns and pension reforms on the future level of public pensions across birth cohorts in Germany. The analysis is based on a microsimulation model and a rich data set that combines household survey data from the German Socio-Economic Panel Study (SOEP) and process-produced microdata from the German pension insurance. We account for cohort effects in individual employment and unemployment affecting earnings over the life cycle as well as the differential impact of recent pension reforms. For individuals born between 1937 and 1971, cohort effects vary greatly by region, gender and education, and strongly affect life cycle earnings profiles. The largest effects can be observed for younger cohorts in East Germany and for the low educated. Using simulated life cycle employment and income profiles, we project gross future pensions across cohorts taking into account changing demographics and recent pension reforms. Simulations show that pension levels for East German men and women will fall dramatically among younger birth cohorts, not only because of policy reforms but also due to higher cumulated unemployment. For West German men, the small reduction of average pension levels among younger birth cohorts is mainly driven by the impact of pension reforms, while future pension levels of West German women are increasing or stable due to rising labour market participation of younger birth cohorts.
On the Inappropriateness of Using Items to Calculate Total Scale Score Reliability via Coefficient Alpha for Multidimensional Scales
Authors: Gignac Gilles E.
Published: November 2013

Researchers have the implicit option of calculating internal consistency reliability (coefficient α) for total scale scores derived from multidimensional inventories based on either the inter-item correlation matrix (item unit-level) or the inter-subscale correlation matrix (subscale unit-level). It is demonstrated that item unit-level and subscale unit-level reliability estimates often diverge substantially in practice. Specifically, the item unit-level reliability estimation is often larger than the corresponding subscale unit-level estimate. It is recommended that if researchers calculate total scale score reliability at the item unit-level, then a model-based approach to the estimation of internal consistency reliability (i.e., omega hierarchical) should be applied, when the underlying model is multidimensional. If omega hierarchical cannot be applied for any particular reason, it is recommended that total scale score reliabilities be calculated at the subscale unit-level of analysis, not the item unit-level.
Economic Games
Authors: Baumert Anna , Schlösser Thomas , Schmitt Manfred
Published: November 2013

The psychometric properties of behaviors in economic games as indicators of stable latent dispositions of altruism and fairness were tested in two studies. Using latent state-trait analyses, we explored the factor structure of offers in the dictator game, rejection decisions in the ultimatum game, and altruistic punishment and altruistic compensation in a three-person game. Results showed that four distinct but intercorrelated latent dispositions best described the interindividual differences in these behaviors. The reliabilities and stabilities of these behaviors across 6 weeks were generally moderate to high. Correlations with self-report measures of personality suggested that offers in the dictator game and altruistic compensation reflect a concern for fairness coupled with a reluctance to harm others. Rejection decisions in the ultimatum game were correlated with competitiveness and the need for power. In sum, our results suggest that economic games have good psychometric qualities as instruments that can be used to assess stable latent dispositions and can be employed as objective personality tests sensu Cattell to gain a more complete picture of personality beyond self-reports.
Age-Related Decline in Emotional Prosody Discrimination
Authors: Mitchell Rachel L. C. , Kingston Rachel A.
Published: November 2013

It is now accepted that older adults have difficulty recognizing prosodic emotion cues, but it is not clear at what processing stage this ability breaks down. We manipulated the acoustic characteristics of tones in pitch, amplitude, and duration discrimination tasks to assess whether impaired basic auditory perception coexisted with our previously demonstrated age-related prosodic emotion perception impairment. It was found that pitch perception was particularly impaired in older adults, and that it displayed the strongest correlation with prosodic emotion discrimination. We conclude that an important cause of age-related impairment in prosodic emotion comprehension exists at the fundamental sensory level of processing.
Impact of Feedback on Three Phases of Performance Monitoring
Authors: Appelgren Alva , Penny William , Bengtsson Sara L
Published: November 2013

We investigated if certain phases of performance monitoring show differential sensitivity to external feedback and thus rely on distinct mechanisms. The phases of interest were: the error phase (FE), the phase of the correct response after errors (FEC), and the phase of correct responses following corrects (FCC). We tested accuracy and reaction time (RT) on 12 conditions of a continuous-choice-response task; the 2-back task. External feedback was either presented or not in FE and FEC, and delivered on 0%, 20%, or 100% of FCC trials. The FCC20 was matched to FE and FEC in the number of sounds received so that we could investigate when external feedback was most valuable to the participants. We found that external feedback led to a reduction in accuracy when presented on all the correct responses. Moreover, RT was significantly reduced for FCC100, which in turn correlated with the accuracy reduction. Interestingly, the correct response after an error was particularly sensitive to external feedback since accuracy was reduced when external feedback was presented during this phase but not for FCC20. Notably, error-monitoring was not influenced by feedback-type. The results are in line with models suggesting that the internal error-monitoring system is sufficient in cognitively demanding tasks where performance is ∼ 80%, as well as theories stipulating that external feedback directs attention away from the task. Our data highlight the first correct response after an error as particularly sensitive to external feedback, suggesting that important consolidation of response strategy takes place here.
A pharmaco‐epistasis strategy reveals a new cell size controlling pathway in yeast
Authors: Moretto Fabien , Sagot Isabelle , Daignan‐Fornier Bertrand , Pinson Benoît
Published: November 2013

Cell size is a complex quantitative trait resulting from interactions between intricate genetic networks and environmental conditions. Here, taking advantage of previous studies that uncovered hundreds of genes affecting budding yeast cell size homeostasis, we performed a wide pharmaco‐epistasis analysis using drugs mimicking cell size mutations. Simple epistasis relationship emerging from this approach allowed us to characterize a new cell size homeostasis pathway comprising the sirtuin Sir2, downstream effectors including the large ribosomal subunit (60S) and the transcriptional regulators Swi4 and Swi6. We showed that this Sir2/60S signaling route acts independently of other previously described cell size controlling pathways and may integrate the metabolic status of the cell through NAD+ intracellular concentration. Finally, although Sir2 and the 60S subunits regulate both cell size and replicative aging, we found that there is no clear causal relationship between these two complex traits. This study sheds light on a pathway of >50 genes and illustrates how pharmaco‐epistasis applied to yeast offers a potent experimental framework to explore complex genotype/phenotype relationships.
Relaxin and its role in fibrotic diseases
Authors: Chan Linda Jiaying , Samuel Chrishan S. , Separovic Frances , Hossain Mohammed Akhter , Wade John D.
Published: November 2013

Relaxin is a member of the insulin family of peptides. It is produced in the corpus luteum and/or placenta during pregnancy in mammals and is secreted into the blood where it has numerous essential endocrine functions. In addition to long-recognized roles in remodeling of reproductive tissues, it has an important role as a cardiovascular hormone during pregnancy with potent vasodilatory and renal actions. Additionally, relaxin has potent effects on collagen turnover in connective tissue. The positive effects of relaxin in induced fibrosis models show a significant role in ameliorating kidney, heart and lung fibrosis. Much work has thus been undertaken on the structure and function relationship of this peptide with the goal of understanding the molecular basis for relaxin's action and developing mimetics with potential therapeutic applications in fibrosis.
Experimental investigation of the mechanical grinding effect on graphene structure
Authors: Myekhlai Munkhshur , Munkhbayar B. , Lee Taejin , Tanshen Md. Riyad , Chung Hanshik , Jeong Hyomin
Published: November 2013

The improvements in dispersion and thermal characteristics of a graphene–water solution were investigated based on the morphological and structural changes.
Light ion production for a future radiobiological facility at CERN: Preliminary studies
Authors: Stafford-Haworth Joshua , Bellodi Giulia , Küchler Detlef , Lombardi Alessandra , Röhrich Jörg , Scrivens Richard
Published: November 2013

Recent medical applications of ions such as carbon and helium have proved extremely effective for the treatment of human patients. However, before now a comprehensive study of the effects of different light ions on organic targets has not been completed. There is a strong desire for a dedicated facility which can produce ions in the range of protons to neon in order to perform this study. This paper will present the proposal and preliminary investigations into the production of light ions, and the development of a radiobiological research facility at CERN. The aims of this project will be presented along with the modifications required to the existing linear accelerator (Linac3), and the foreseen facility, including the requirements for an ion source in terms of some of the specification parameters and the flexibility of operation for different ion types. Preliminary results from beam transport simulations will be presented, in addition to some planned tests required to produce some of the required light ions (lithium, boron) to be conducted in collaboration with the Helmholtz-Zentrum für Materialien und Energie, Berlin.
Rear illumination monolithically integrated GaSb thermophotovoltaic devices grown on semi-insulating GaAs substrate
Authors: Borrego J. M. , Brown E. , Greiff P. , Huffaker D. L. , Laghumavarapu R. B. , Kim J. , Dutta P. S.
Published: November 2013

This paper presents the device design, modeling, materials growth, and device fabrication results of wafer scale monolithically integrated modules (MIMs) of series interconnected GaSb thermo-photovoltaic (TPV) cells grown on 50 mm diameter semi-insulating (SI) GaAs substrates. The feasibility of using GaSb epi-layers grown on SI GaAs for fabricating modules of photovoltaic (PV) cells connected in series for the conversion of low temperature heat radiating sources into electrical energy has been demonstrated. Device modeling shows that assuming an Shockley-Read-Hall recombination lifetime of 100 ns, in addition to intrinsic radiative and Auger recombination in GaSb, it is possible to design PV cells that when placed at sub-micron distance from a 900 °C radiating source are able to convert the heat into electrical energy at a power density of 1.5 to 3 W/cm2 using GaSb epi-layers grown on SI GaAs. The advantage of using SI GaAs is that it is possible to produce MIM modules of PV cells that can have output voltages of 6 V to 10 V decreasing the internal resistance of the PV cell. The device design and fabrication process presented here can be used for large area device arrays high efficiency solar photovoltaic cells employing other semiconductor materials for terrestrial and space applications with back-side illumination architecture.
Nonlinear intrinsic variables and state reconstruction in multiscale simulations
Authors: Dsilva Carmeline J. , Talmon Ronen , Rabin Neta , Coifman Ronald R. , Kevrekidis Ioannis G.
Published: November 2013

Finding informative low-dimensional descriptions of high-dimensional simulation data (like the ones arising in molecular dynamics or kinetic Monte Carlo simulations of physical and chemical processes) is crucial to understanding physical phenomena, and can also dramatically assist in accelerating the simulations themselves. In this paper, we discuss and illustrate the use of nonlinear intrinsic variables (NIV) in the mining of high-dimensional multiscale simulation data. In particular, we focus on the way NIV allows us to functionally merge different simulation ensembles, and different partial observations of these ensembles, as well as to infer variables not explicitly measured. The approach relies on certain simple features of the underlying process variability to filter out measurement noise and systematically recover a unique reference coordinate frame. We illustrate the approach through two distinct sets of atomistic simulations: a stochastic simulation of an enzyme reaction network exhibiting both fast and slow time scales, and a molecular dynamics simulation of alanine dipeptide in explicit water.
Nonlocal operators, parabolic-type equations, and ultrametric random walks
Authors: Chacón-Cortes L. F. , Zúñiga-Galindo W. A.
Published: November 2013

In this article, we introduce a new type of nonlocal operators and study the Cauchy problem for certain parabolic-type pseudodifferential equations naturally associated to these operators. Some of these equations are the p-adic master equations of certain models of complex systems introduced by Avetisov, V. A. and Bikulov, A. Kh., “On the ultrametricity of the fluctuation dynamicmobility of protein molecules,” Proc. Steklov Inst. Math. 265(1), 75–81 (2009) [Tr. Mat. Inst. Steklova 265, 82–89 (2009) (Izbrannye Voprosy Matematicheskoy Fiziki i p-adicheskogo Analiza) (in Russian)]; Avetisov, V. A., Bikulov, A. Kh., and Zubarev, A. P., “First passage time distribution and the number of returns for ultrametric random walks,” J. Phys. A 42(8), 085003 (2009); Avetisov, V. A., Bikulov, A. Kh., and Osipov, V. A., “p-adic models of ultrametric diffusion in the conformational dynamics of macromolecules,” Proc. Steklov Inst. Math. 245(2), 48–57 (2004) [Tr. Mat. Inst. Steklova 245, 55–64 (2004) (Izbrannye Voprosy Matematicheskoy Fiziki i p-adicheskogo Analiza) (in Russian)]; Avetisov, V. A., Bikulov, A. Kh., and Osipov, V. A., “p-adic description of characteristic relaxation in complex systems,” J. Phys. A 36(15), 4239–4246 (2003); Avetisov, V. A., Bikulov, A. H., Kozyrev, S. V., and Osipov, V. A., “p-adic models of ultrametric diffusion constrained by hierarchical energy landscapes,” J. Phys. A 35(2), 177–189 (2002); Avetisov, V. A., Bikulov, A. Kh., and Kozyrev, S. V., “Description of logarithmic relaxation by a model of a hierarchical random walk,” Dokl. Akad. Nauk 368(2), 164–167 (1999) (in Russian). The fundamental solutions of these parabolic-type equations are transition functions of random walks on the n-dimensional vector space over the field of p-adic numbers. We study some properties of these random walks, including the first passage time.
Multi-view fast-ion D-alpha spectroscopy diagnostic at ASDEX Upgrade
Authors: Geiger B. , Dux R. , McDermott R. M. , Potzel S. , Reich M. , Ryter F. , Weiland M. , Wünderlich D. ,   ASDEX Upgrade Team, Garcia-Munoz M.
Published: November 2013

A novel fast-ion D-alpha (FIDA) diagnostic that is based on charge exchange spectroscopy has been installed at ASDEX Upgrade. The diagnostic uses a newly developed high-photon-throughput spectrometer together with a low-noise EM-CCD camera that allow measurements with 2 ms exposure time. Absolute intensities are obtained by calibrating the system with an integrating sphere and the wavelength dependence is determined to high accuracy using a neon lamp. Additional perturbative contributions to the spectra, such as \documentclass[12pt]{minimal}\begin{document}$\rm {D_2}$\end{document}D2-molecular lines, the Stark broadened edge D-alpha emission, and passive FIDA radiation have been identified and can be subtracted or avoided experimentally. The FIDA radiation from fast deuterium ions after charge exchange reactions can therefore be analyzed continuously without superimposed line emissions at large Doppler shifts. Radial information on the fast ions is obtained from radially distributed lines of sight. The investigation of the fast-ion velocity distribution is possible due to three different viewing geometries. The independent viewing geometries access distinct parts of the fast-ion velocity space and make tomographic reconstructions possible.
Effect of Ta thickness on the perpendicular magnetic anisotropy in MgO/CoFeB/Ta/[Co/Pd]n structures
Authors: Chang Yao-Jen , Canizo-Cabrera A. , Garcia-Vazquez Valentin , Chang Yang-Hua , Wu Te-ho
Published: November 2013

We studied the effect of a thin Ta layer on the perpendicular magnetic anisotropy (PMA) of composite FM1/Ta/FM2 magnetic structures, where FM1 represents the subsystem MgO/CoFeB, and FM2 denotes a [Co/Pd]6 multilayer. The stack without Ta spacer layer shows no PMA. Once a Ta layer is inserted between the thin CoFeB layer and the [Co/Pd]6 multilayer, PMA is observed. The perpendicular magnetization loops show squareness ratios close to unity, indicating the presence of almost complete perpendicular anisotropy. These hysteresis loops also show sharp switching characteristics, indicating that the MgO/CoFeB bilayer and the [Co/Pd]6 multilayer are ferromagnetically coupled together. The coercive field Hc of the composite structure increases as Ta thickness increases. Our results show that Ta layer is essential for integrating MgO/CoFeB and [Co/Pd]6 into a composite magnetic structure with perpendicular anisotropy.
An exciton-polariton mediated all-optical router
Authors: Flayac H. , Savenko I. G.
Published: November 2013

We propose an all-optical nonlinear router based on a double barrier gate connected to periodically modulated guides. A semiconductor microcavity is driven nonresonantly in-between the barriers to form an exciton-polariton condensate on a discrete state that is subject to the exciton blueshift. The subsequent coherent optical signal is allowed to propagate through a guide provided that the condensate energy is resonant with a miniband or is blocked if it faces a gap. While a symmetric sample operates as an optical switch, its asymmetric counterpart embodies a router turned to be polarization selective under applied magnetic field.
Analysis of critical process optimization in the black liquor gasification system
Authors: Lv Ganglin , Su Jixin , Zhang Lin , Li Qun , Xu Li , Zhao Lining
Published: November 2013

The energy balance of the black liquor gasification (BLG) system, which is the core part in the Pulp-Syngas-Heat and Electricity combined cycle system, was analysed in this paper. Based on existing engineering parameters, we compared the energy consumption, conversion efficiency and energy cost of the BLG system under the different process conditions, in particular the air separation and concentration sections. Comparative analysis of these critical processes would facilitate the optimization of energy conversion efficiency and energy cost, as well as ascertain the influence of electricity and heat price on them. Results showed the drive combination of mechanical vapour recompression concentrating black liquor and electric driven preparation of oxygen (MVR-Motor) had the highest energy conversion efficiency of 73.18% but maximal energy cost. The drive combination of multi-effect evaporation concentrating black liquor and back pressure steam turbine preparation of oxygen (MEE-BPST) had the lowest energy cost, despite its energy conversion efficiency a little lower than MVR-Motor. For the drive combination of MVR-Motor, BLG system can get 224.32 kgce net energy output per 1000 kg straw pulp. Selection of reasonable process technology would promote the commercialization of BLG and the links to paper industry, biomass energy industry, and chemical industry, which benefits the control of black liquor pollution.
Highly efficient terahertz detection by optical mixing in a GaAs photoconductor
Authors: Peytavit E. , Pavanello F. , Ducournau G. , Lampin J.-F.
Published: November 2013

It is shown from accurate on-wafer measurement that a low-temperature-grown GaAs photoconductor using a metallic mirror Fabry-Perot cavity can serve as highly efficient optoelectronic heterodyne mixer in the terahertz frequency range. Conversion losses of 22 dB at 100 GHz and ∼27 dB at 300 GHz were measured, which is an improvement by a factor of about 40 dB as compared with the previous values obtained with photoconductors. Experimental results are interpreted satisfactorily by means of a simple electrical model of the optoelectronic mixing process.
Spin current source based on a quantum point contact with local spin-orbit interaction
Authors: Nowak M. P. , Szafran B.
Published: November 2013

Proposal for construction of a source of spin-polarized current based on quantum point contact (QPC) with local spin-orbit interaction is presented. We show that spin-orbit interaction present within the narrowing acts like a spin filter. The spin polarization of the current is discussed as a function of the Fermi energy and the width of the QPC.
Note of clarification about: Oxygenated Terpenoids from the Australian Sponges Coscinoderma matthewsi and Dysidea sp., and the Nudibranch Chromodoris albopunctata [vol. 65, pp. 531–538]
Authors: Katavic Peter L. , Jumaryatno Pinus , Hooper John N. A. , Blanchfield Joanne T. , Garson Mary J.
Published: November 2013

The isolation and structure elucidation of seven new oxygenated terpenoids and eight known terpene metabolites from marine invertebrates collected at the Inner Gneerings Reef, South East Queensland, is discussed. Investigation of the sponge Coscinoderma matthewsi yielded an epoxylactone derivative (1) of the known furanoterpene tetradehydrofurospongin-1 (2). A chemical investigation of the dissected nudibranch Chromodoris albopunctata provided the new oxygenated diterpenes 12?-acetoxyspongian-16-one (10), 20-acetoxyspongian-16-one (12), 20-oxyspongian-16-one propionate (13) and 12?,20-dioxyspongian-16-one dipropionate (14) in conjunction with three other known diterpene metabolites, while two new chromodorolides, D (17) and E (18), in addition to four known diterpenes were isolated from a Dysidea sp.
Genetic variation for resistance to Fusarium head blight in winter durum material
Authors: Miedaner Thomas , Longin Carl Friedrich Horst
Published: November 2013

Durum is one of the most susceptible cereals to infection with Fusarium head blight (FHB) due to the lack of resistance sources. Data on the genetic variation and heritability of FHB in elite durum, and especially the new evolving winter durum, are lacking. Thus, we compared 105 elite, winter durum breeding lines with an international collection of 62 old and new winter durum cultivars. We evaluated the development of FHB after inoculation by Fusarium culmorum, heading time, and plant height at three field environments in Germany. Significant genetic variation for FHB was identified in the elite breeding material as well as in the collection. Mean FHB rating was normally distributed with a heritability of >0.7 for both sets, indicating the quantitative genetic nature of the trait. Taking heading time, plant height, and FHB resistance into account, the most interesting genotypes were identified in the elite breeding material. Consequences for the ongoing global efforts for improvement of FHB resistance of durum are discussed.
Overexpression of Twinkle-helicase protects cardiomyocytes from genotoxic stress caused by reactive oxygen species
Authors: Pohjoismäki Jaakko L. O. , Williams Siôn L. , Boettger Thomas , Goffart Steffi , Kim Johnny , Suomalainen Anu , Moraes Carlos T. , Braun Thomas
Published: November 2013

Significance

In the present work, we show that overexpression of TWINKLE helicase reduces the amount of ROS-induced mtDNA mutations and ameliorates cardiomyopathy in Sod2+/−mice. We demonstrate that increased ROS in mitochondria result in a rise of base transversions and mtDNA rearrangements. Increased TWINKLE availability improves mtDNA integrity and protects cardiomyocytes by inhibiting apoptosis via p21. Our findings offer unique approaches to limit the loss of cardiomyocytes due to oxidative stress, a common problem in various disease conditions and during normal aging.
Site-2 protease substrate specificity and coupling in
trans
by a PDZ-substrate adapter protein
Authors: Schneider Jessica S. , Reddy Shilpa P. , E Hock Y. , Evans Henry W. , Glickman Michael S.
Published: November 2013

Significance

Site-2 proteases are ubiquitously distributed, and yet their regulation and substrate recognition remain poorly understood. Here, we describe a model for site-2 protease regulation in which regulated intramembrane protease 1 (Rip1), a site-2 protease crucial for virulence in
Mycobacterium tuberculosis
, is tethered to one of its substrates by an adapter protein, PDZ-interacting protease regulator (Ppr) 1.
Phosphoproteomic characterization of DNA damage response in melanoma cells following MEK/PI3K dual inhibition
Authors: Kirkpatrick Donald S. , Bustos Daisy J. , Dogan Taner , Chan Jocelyn , Phu Lilian , Young Amy , Friedman Lori S. , Belvin Marcia , Song Qinghua , Bakalarski Corey E. , Hoeflich Klaus P.
Published: November 2013

Significance

Growing evidence suggests that successful intervention in many human cancers will require combinations of therapeutic agents. Critical to this effort will be a detailed understanding of the crosstalk between signaling networks that modulate proliferation, cell death, drug sensitivity, and acquired resistance. Here we investigated DNA-damage signaling elicited by small-molecule inhibitors against MAP/ERK kinase (MEK) and PI3K in melanoma cells. This work, performed using cutting-edge mass spectrometry proteomics, uncovered a burst of signaling among proteins in the DNA-damage pathway upon initiation of the cell-death program by agents targeting the RAS–RAF–MEK and PI3K–AKT–mTOR pathways. These signals may prove important to the short- and long-term sensitivity of tumor cells to MEK- and PI3K-targeted therapies.
Serotonin regulates glucose-stimulated insulin secretion from pancreatic β cells during pregnancy
Authors: Ohara-Imaizumi Mica , Kim Hail , Yoshida Masashi , Fujiwara Tomonori , Aoyagi Kyota , Toyofuku Yukiko , Nakamichi Yoko , Nishiwaki Chiyono , Okamura Tadashi , Uchida Toyoyoshi , Fujitani Yoshio , Akagawa Kimio , Kakei Masafumi , Watada Hirotaka , German Michael S. , Nagamatsu Shinya
Published: November 2013

Significance

During pregnancy, maternal insulin secretion increases markedly. This increase is not simply a response to increased demand, as it precedes the insulin resistance that develops late in pregnancy, nor is it solely a result of increased β cell mass, as secretion per beta cell increases as well. Here we show that the increased islet serotonin induced by pregnancy signals through the 5-HT3 receptor (Htr3) to increase insulin secretion dramatically. Htr3 signaling increases the excitability of the β cell membrane, thereby decreasing the threshold for insulin secretion. These studies elucidate the mechanism for pregnancy-induced increase in insulin release.
Rewriting the rules for end joining via enzymatic splicing of DNA 3′-PO
4
and 5′-OH ends
Authors: Das Ushati , Chakravarty Anupam K. , Remus Barbara S. , Shuman Stewart
Published: November 2013

Significance

The ability to repair breaks in the DNA phosphodiester backbone is essential for genome integrity. When breakage results in 5′-PO
4
and 3′-OH termini, the ends can be rejoined to each other, or to novel partner strands, by classic DNA ligases that covalently activate the 5′-PO
4
end by linkage to AMP. However, when breakage leaves 5′-OH and 3′-PO
4
termini, the ends are considered “dirty” because they cannot be sealed by classic ligases. This paper shows that the unconventional ligase RtcB can evade the DNA dirty end chemistry problem by splicing DNA 3′-PO
4
ends to DNA 5′-OH ends. RtcB accomplishes this by attaching a GMP nucleotide to the DNA 3′-PO
4
end to activate it for nucleophilic attack by the 5′-OH.
Structural insights into the histone H1-nucleosome complex
Authors: Zhou Bing-Rui , Feng Hanqiao , Kato Hidenori , Dai Liang , Yang Yuedong , Zhou Yaoqi , Bai Yawen
Published: November 2013

Significance

Linker H1 histones control the accessibility of linker DNA between two neighbor nucleosomes to DNA-binding proteins and regulate chromatin folding. We investigated the structure of the H1–nucleosome complex through a combination of multidimensional nuclear magnetic resonance spectroscopy, site-directed mutagenesis-isothermal-titration calorimetry and computational design/modeling. The results lead to a unique structural model for the globular domain of H1 in complex with the nucleosome that contains residue-level information and have implications for the dynamics of chromatin in vivo. In addition, our approach will be useful for testing the hypothesis that the globular domain of H1 variants might have distinct binding geometries within the nucleosome, and thereby contribute to the heterogeneity of chromatin structure.
Hox5
interacts with
Plzf
to restrict
Shh
expression in the developing forelimb
Authors: Xu Ben , Hrycaj Steven M. , McIntyre Daniel C. , Baker Nicholas C. , Takeuchi Jun K. , Jeannotte Lucie , Gaber Zachary B. , Novitch Bennett G. , Wellik Deneen M.
Published: November 2013

Significance

Mammalian
Hox
genes are important for limb development. Posterior
abdominal B
(
AbdB
)
Hox
groups (
Hox9
–
Hox13
) are required for establishment of the limb proximodistal axis. In addition,
Hox9
genes control the onset of
Hand2
expression in the posterior forelimb, and
HoxA/D
AbdB
genes are responsible for the initiation and maintenances of
Sonic Hedgehog
(
Shh
). In this study, we generated
Hox5
triple mutants, resulting in embryos with severe forelimb anterior patterning defects. We found that Hox5 proteins interact with
promyelocytic leukemia zinc finger
to restrict
Shh
expression in the forelimb bud. The hindlimb in
Hox5
mutants develops normally, revealing distinct differences in anteroposterior field establishment in the forelimb and hindlimb and unanticipated roles for non-
AbdB Hox
genes, including
HoxB
and
HoxC
group genes, in limb development.
Sonic hedgehog signals to multiple prostate stromal stem cells that replenish distinct stromal subtypes during regeneration
Authors: Peng Yu-Ching , Levine Charles M. , Zahid Sarwar , Wilson E. Lynette , Joyner Alexandra L.
Published: November 2013

Significance

Sonic hedgehog (SHH) signaling regulates adult stem cells in many self-renewing organs. However, whether SHH also regulates adult stem cells in tissues like the prostate is unclear. Improving therapy for prostate diseases, including benign prostatic hyperplasia and prostate cancer, will require a better understanding of the key signaling pathways that regulate prostate homeostasis and regeneration. We show that SHH signals from basal epithelial cells to the surrounding stroma in the adult prostate. Moreover, SHH responding cells repopulate the stroma and exhibit long-term self-renewal capacity during multiple rounds of involution and regeneration. Furthermore, we identified four stromal subtypes and present evidence for a model in which the three ductal stromal subtypes are maintained largely by distinct unipotent stem/progenitor cells.
The EM structure of the TRAPPIII complex leads to the identification of a requirement for COPII vesicles on the macroautophagy pathway
Authors: Tan Dongyan , Cai Yiying , Wang Juan , Zhang Jinzhong , Menon Shekar , Chou Hui-Ting , Ferro-Novick Susan , Reinisch Karin M. , Walz Thomas
Published: November 2013

Significance

Rab GTPases are critical determinants of membrane identity in eukaryotic cells. Typically, each GTPase is activated by a single guanine nucleotide exchange factor (GEF), but the Ypt1/Rab1 GTPase is activated by three related GEFs, transport protein particle (TRAPP) I, TRAPPII, and TRAPPIII, that function in distinct trafficking pathways. TRAPPIII is recruited to the phagophore assembly site when macroautophagy is induced. Here, we present the single-particle electron microscopy structure of TRAPPIII and evidence that TRAPPIII binds the coat protein complex (COP) II coat. We also show that the ER-Golgi fusion machinery that is present on COPII vesicles is needed for macroautophagy. Our results imply that TRAPPIII recruits COPII vesicles to the PAS and that COPII vesicles may provide one of the membrane sources used in autophagosome formation.
BMP9 ameliorates amyloidosis and the cholinergic defect in a mouse model of Alzheimer’s disease
Authors: Burke Rebecca M. , Norman Timothy A. , Haydar Tarik F. , Slack Barbara E. , Leeman Susan E. , Blusztajn Jan Krzysztof , Mellott Tiffany J.
Published: November 2013

Significance

Bone morphogenetic protein 9 (BMP9) is a trophic factor for basal forebrain cholinergic neurons (BFCN) and constitutes a candidate therapeutic molecule for diseases characterized by BFCN dysfunction. A prominent example of such an illness, for which effective therapies are critically needed, is Alzheimer’s disease (AD). A decline in BFCN function and diminished cholinergic marker expression occurs in brains of patients with AD and is observed in AD animal models. We report that BMP9 administration is effective in reducing the amyloid plaque burden, reversing cholinergic neuron abnormalities, and generating a neurotrophic milieu for cholinergic neurons in a mouse model of AD, thus providing evidence that the BMP9-signaling pathway may constitute a novel therapeutic target in AD.
Adult Recollections of Childhood Memories: What Details can be Recalled?
Authors: Wells Christine , Morrison Catriona M. , Conway Martin A.
Published: November 2013

In a memory survey, adult respondents recalled, dated, and described two earliest positive and negative memories that they were highly confident were memories. They then answered a series of questions that focused on memory details such as clothing, duration, weather, and so on. Few differences were found between positive and negative memories, which on average had 4/5 details and dated to the age of 6/6.5 years. Memory for details about activity, location, and who was present was good; memory for all other details was poorer or at floor. Taken together, these findings indicate that (full) earliest memories may be considerably later than previously thought and that they rarely contain the sort of specific details targeted by professional investigators. The resulting normative profile of memory details reported here can be used to evaluate overly specific childhood autobiographical memories and to identify memory details with a low probability of recall.
Religion and the state in contemporary Arab society: theoretically, practically and prospectively
Authors: Belkeziz Abdelilah
Published: November 2013

Through an examination of the different types of relationships between religion and the state, this article argues that the two extremes of this relationship – namely, the case whereby the state exploits religion and the one where it tries to banish it – ultimately lead to the emergence of political Islam as a reaction. Political Islam can be seen as employing religion to gain political power, hence reinforcing the worldly aspects and self-interest of a certain group at the expense of intellectual, ethical and doctrinal considerations. Practically speaking, political Islam has pushed the idea of an Islamic state to suicidal theocratic ends. The main factor behind the ascent of Islamists to political power is the political vacuum resulting from the retreat of the left, added to absolute obstructionism in the political domain. In an attempt to redeem religion and the state in contemporary Arab society and end the struggle between Islamists and secularists, four suggestions are presented: (1) recognition of the right of any political movement to derive its basic ethos from religion, or religious heritage, on condition that this is considered a personal endeavour rather than a religious issue; (2) stressing the civil nature of all parties, whether secular or religious; (3) respecting the civil nature of the state; and (4) abiding by the democratic circulation of power. In sum, a revitalization of the modern state system is inevitable.
Representations of religion in secular states: the Muslim communities in Sweden
Authors: Lagervall Rickard
Published: November 2013

The presence of Muslim populations in Western European societies is a relatively new phenomenon which is raising questions about how these societies treat religious minorities. This article considers the situation in Sweden, beginning with a brief history of the development of the Swedish state from one based on the Lutheran faith to today’s secular society in which state and religion are officially separated. It moves on to discuss the emergence of a sizable Muslim population in the latter part of the 20th century and considers the ways in which the secular character and religious neutrality of the state offer such religious minorities space to practise their religions. However, as Swedish society, politics and law are still premised on certain Christian notions of what religion should be, Muslims and more particularly Islamic organizations in the country have to find ways to adapt themselves to these pre-existing religious structures. Thus the presence of a large Muslim minority has affected the mindset of the members of this minority as well as the Swedish host society.
Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo
Authors: Abdel-Wahab Omar , Gao Jie , Adli Mazhar , Dey Anwesha , Trimarchi Thomas , Chung Young Rock , Kuscu Cem , Hricik Todd , Ndiaye-Lobry Delphine , LaFave Lindsay M. , Koche Richard , Shih Alan H. , Guryanova Olga A. , Kim Eunhee , Li Sheng , Pandey Suveg , Shin Joseph Y. , Telis Leon , Liu Jinfeng , Bhatt Parva K. , Monette Sebastien , Zhao Xinyang , Mason Christopher E. , Park Christopher Y. , Bernstein Bradley E. , Aifantis Iannis , Levine Ross L.
Published: November 2013

Somatic Addition of Sex Combs Like 1 (ASXL1) mutations occur in 10–30% of patients with myeloid malignancies, most commonly in myelodysplastic syndromes (MDSs), and are associated with adverse outcome. Germline ASXL1 mutations occur in patients with Bohring-Opitz syndrome. Here, we show that constitutive loss of Asxl1 results in developmental abnormalities, including anophthalmia, microcephaly, cleft palates, and mandibular malformations. In contrast, hematopoietic-specific deletion of Asxl1 results in progressive, multilineage cytopenias and dysplasia in the context of increased numbers of hematopoietic stem/progenitor cells, characteristic features of human MDS. Serial transplantation of Asxl1-null hematopoietic cells results in a lethal myeloid disorder at a shorter latency than primary Asxl1 knockout (KO) mice. Asxl1 deletion reduces hematopoietic stem cell self-renewal, which is restored by concomitant deletion of Tet2, a gene commonly co-mutated with ASXL1 in MDS patients. Moreover, compound Asxl1/Tet2 deletion results in an MDS phenotype with hastened death compared with single-gene KO mice. Asxl1 loss results in a global reduction of H3K27 trimethylation and dysregulated expression of known regulators of hematopoiesis. RNA-Seq/ChIP-Seq analyses of Asxl1 in hematopoietic cells identify a subset of differentially expressed genes as direct targets of Asxl1. These findings underscore the importance of Asxl1 in Polycomb group function, development, and hematopoiesis.
Peregrination of the selectivity filter delineates the pore of the human voltage-gated proton channel hHV1
Authors: Morgan Deri , Musset Boris , Kulleperuma Kethika , Smith Susan M.E. , Rajan Sindhu , Cherny Vladimir V. , Pomès Régis , DeCoursey Thomas E.
Published: November 2013

Extraordinary selectivity is crucial to all proton-conducting molecules, including the human voltage-gated proton channel (hHV1), because the proton concentration is >106 times lower than that of other cations. Here we use “selectivity filter scanning” to elucidate the molecular requirements for proton-specific conduction in hHV1. Asp112, in the middle of the S1 transmembrane helix, is an essential part of the selectivity filter in wild-type (WT) channels. After neutralizing Asp112 by mutating it to Ala (D112A), we introduced Asp at each position along S1 from 108 to 118, searching for “second site suppressor” activity. Surprisingly, most mutants lacked even the anion conduction exhibited by D112A. Proton-specific conduction was restored only with Asp or Glu at position 116. The D112V/V116D channel strikingly resembled WT in selectivity, kinetics, and ΔpH-dependent gating. The S4 segment of this mutant has similar accessibility to WT in open channels, because R211H/D112V/V116D was inhibited by internally applied Zn2+. Asp at position 109 allowed anion permeation in combination with D112A but did not rescue function in the nonconducting D112V mutant, indicating that selectivity is established externally to the constriction at F150. The three positions that permitted conduction all line the pore in our homology model, clearly delineating the conduction pathway. Evidently, a carboxyl group must face the pore directly to enable conduction. Molecular dynamics simulations indicate reorganization of hydrogen bond networks in the external vestibule in D112V/V116D. At both positions where it produces proton selectivity, Asp frequently engages in salt linkage with one or more Arg residues from S4. Surprisingly, mean hydration profiles were similar in proton-selective, anion-permeable, and nonconducting constructs. That the selectivity filter functions in a new location helps to define local environmental features required to produce proton-selective conduction.
Correct developmental expression level of Rai1 in forebrain neurons is required for control of body weight, activity levels and learning and memory
Authors: Cao Lei , Molina Jessica , Abad Clemer , Carmona-Mora Paulina , Cárdenas Oyarzo Areli , Young Juan I. , Walz Katherina
Published: November 2013

Potocki–Lupski syndrome (PTLS) is a genomic disorder associated with an ∼3 Mb duplication in 17p11.2. Clinical features include leanness, intellectual disability, autistic features and developmental deficits. RAI1 gene dosage is associated with the PTLS phenotypes. To understand where and when Rai1 overexpression is detrimental, we generated a mouse that over-expresses Rai1 conditionally in forebrain neurons (I-Rai1). Phenotypic characterization of I-Rai1 mice showed significant underweight, hyperactivity and impaired learning and memory ability compared with wild-type littermates. Doxycycline administration can turn off the transgene expression allowing the restoration of Rai1 normal expression levels. When the transgene was turned off from conception to 3 months of age, no phenotypic differences were observed between I-Rai1 and their wild-type littermates. Surprisingly, we found that turning off the transgene expression before the onset of the phenotypes (1–3 months) or after the onset of the phenotypes (3–5 months) cannot prevent nor reverse the phenotypic outcomes. Our results indicate that Rai1 dosage in forebrain neurons is critical during the development and is related to body weight regulation, activity levels and learning and memory.
Comparative receptor tyrosine kinase profiling identifies a novel role for AXL in human stem cell pluripotency
Authors: Son Mi-Young , Seol Binna , Han Yong-Mahn , Cho Yee Sook
Published: November 2013

The extensive molecular characterization of human pluripotent stem cells (hPSCs), human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) is required before they can be applied in the future for personalized medicine and drug discovery. Despite the efforts that have been made with kinome analyses, we still lack in-depth insights into the molecular signatures of receptor tyrosine kinases (RTKs) that are related to pluripotency. Here, we present the first detailed and distinct repertoire of RTK characteristic for hPSC pluripotency by determining both the expression and phosphorylation profiles of RTKs in hESCs and hiPSCs using reverse transcriptase–polymerase chain reaction with degenerate primers that target conserved tyrosine kinase domains and phospho-RTK array, respectively. Among the RTKs tested, the up-regulation of EPHA1, ERBB2, FGFR4 and VEGFR2 and the down-regulation of AXL, EPHA4, PDGFRB and TYRO3 in terms of both their expression and phosphorylation levels were predominantly related to the maintenance of hPSC pluripotency. Notably, the specific inhibition of AXL was significantly advantageous in maintaining undifferentiated hESCs and hiPSCs and for the overall efficiency and kinetics of hiPSC generation. Additionally, a global phosphoproteomic analysis showed that ∼30% of the proteins (293 of 970 phosphoproteins) showed differential phosphorylation upon AXL inhibition in undifferentiated hPSCs, revealing the potential contribution of AXL-mediated phosphorylation dynamics to pluripotency-related signaling networks. Our findings provide a novel molecular signature of AXL in pluripotency control that will complement existing pluripotency-kinome networks.
Discover context-specific combinatorial transcription factor interactions by integrating diverse ChIP-Seq data sets
Authors: Teng Li , He Bing , Gao Peng , Gao Long , Tan Kai
Published: November 2013

Combinatorial interactions among transcription factors (TFs) are critical for integrating diverse intrinsic and extrinsic signals, fine-tuning regulatory output and increasing the robustness and plasticity of regulatory systems. Current knowledge about combinatorial regulation is rather limited due to the lack of suitable experimental technologies and bioinformatics tools. The rapid accumulation of ChIP-Seq data has provided genome-wide occupancy maps for a large number of TFs and chromatin modification marks for identifying enhancers without knowing individual TF binding sites. Integration of the two data types has not been researched extensively, resulting in underused data and missed opportunities. We describe a novel method for discovering frequent combinatorial occupancy patterns by multiple TFs at enhancers. Our method is based on probabilistic item set mining and takes into account uncertainty in both types of ChIP-Seq data. By joint analysis of 108 TFs in four human cell types, we found that cell–type-specific interactions among TFs are abundant and that the majority of enhancers have flexible architecture. We show that several families of transposable elements disproportionally overlap with enhancers with combinatorial patterns, suggesting that these transposable element families play an important role in the evolution of combinatorial regulation.