bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of an evolutionary deglaciation model for the Irish midlands based on the integration of morphostratigraphic and geophysical data analyses
Authors: Pellicer Xavier M. , Warren William P. , Gibson Paul , Linares Rogelio
Published: November 2012

Alternative, established models for the deglaciation of the midlands of Ireland are tested against an interpretation of a suite of deglacial sediments covering an area of 600 km2 in the east central midland area. Interpretation of the sediments is based on geomorphological mapping, lithostratigraphic characterization of exposures and geotechnical data supported by electrical resistivity tomography (ERT) and ground penetrating radar (GPR). GPR depicted small‐scale sedimentological and deformational structures within low‐conductivity soft sediments, such as cross‐bedding, planar bedding, channel‐like features and faulting planes, and revealed the internal architecture of eskers, glaciodeltas, subaqueous fans and raised bogs. ERT data permitted the detection of depth to bedrock and the lithological characterization of unconsolidated sediments. The ten sites presented were surveyed by traditional mapping methods and/or geophysical techniques. This allowed the construction of a local model of the deglaciation of the area which recognized five main stages. An ice sheet covering most of Ireland withdrew as a single body as far as the midlands. At this stage, two main directions of ice retreat are identified from the spatial distribution of meltwater/overflow channels, esker and morainic ridges, and ice‐marginal glaciolacustrine deposits. A pattern of deglacial sedimentation into an expanding ice‐marginal glacial lake is depicted. The glacial lake was dammed to the west by two ice dome fronts, one decaying to the north‐west and another to the south‐west, and by the Shannon Basin watershed to the east. Glacial lake outlets identified along the watershed and the altitude of the topset/foreset interface zone depicted in glaciodeltaic deposits allowed the identification of three lake water levels. The highest level is at 87–89 m Ordnance Datum (OD), the second lake level at 84 m OD and the third at 78 m OD. Copyright © 2012 John Wiley & Sons, Ltd.
New Amphiphilic Conjugates of Amino–Poly(ethylene glycols) With Lipoamino Acids as Surface Modifiers of Colloidal Drug Carriers
Authors: Pignatello Rosario , Pantò Valentina , Impallomeni Giuseppe , Carnemolla Giovanni Marco , Carbone Claudia , Puglisi Giovanni
Published: November 2012

Poly(ethylene glycol) (PEG2000) polymers containing one or two amine residues are linked to α‐lipoamino acids (LAA) to produce mono‐ and homo‐disubstituted PEG–LAA conjugates as new materials for the surface coating of colloidal drug carriers. Conjugates are characterized by FT‐IR, 1H‐NMR, and MALDI–TOF mass spectrometry. Differential scanning calorimetry studies are performed to assess the interaction of PEG2000–LAAs with a biomembrane model (dipalmitoylphosphatidylcholine multilamellar liposomes). Whereas the parent PEGs affect only the superficial structure of the bilayers, the amphiphilic PEG–LAA conjugates exert a modulated perturbing effect on the thermotropic profile of liposomes. A molar concentration between 5% and 10% is individuated as the more suitable to produce stable vesicles.
Does a vascular supercharge improve the clinical outcome for free jejunal transfer?
Authors: Numajiri Toshiaki , Sowa Yoshihiro , Nishino Kenichi , Fujiwara Hitoshi , Nakano Hiroshi , Shimada Taketoshi , Hisa Yasuo
Published: November 2012

To clarify whether a supercharged free jejunal transfer would have a different clinical outcome from the usual transfer method, we examined clinical data from cases of esophago‐pharyngeal reconstruction. Fifty‐three patients in whom the hypopharynx and cervical esophagus was reconstructed with a free jejunal transfer were divided into two groups: 19 normal procedures and 34 supercharged. Clinical outcomes including intraoperative and postoperative events, complications and deglutition were compared statistically. There were no significant differences between the groups in terms of the rates of free flap failure, leakage, stenosis, drinking status, dysphagia, or operating time. There were no significant advantages in clinical outcomes when using a supercharge. However, supercharged flaps with an intraoperative arterial thrombosis were all rescued and survived. Thus, a supercharge in free flap is not necessary for all cases. Its indication should be limited to cases when free flaps are not reliable because of intraoperative thrombosis and arterial insufficiency. © 2012 Wiley Periodicals, Inc. Microsurgery, 2013.
Sensorimotor polyneuropathy in patients with SMA type‐1: Electroneuromyographic findings
Authors: Duman Ozgur , Uysal Hilmi , Skjei Karen L. , Kizilay Ferah , Karauzum Sibel , Haspolat Senay
Published: November 2012

Introduction: Generally, spinal muscular atrophy (SMA) is believed to be a pure motor neuron disease. We retrospectively evaluated our electrodiagnostic findings in SMA type 1 patients to demonstrate co‐existence of sensorimotor neuropathies. Methods: Electroneuromyographic (ENMG) studies in 15 patients (11 boys, 4 girls) were reviewed independently by 2 neurophysiologists. Upper extremity findings were compared with normal right arm controls. Results: Patient ages ranged from 1.5 to 26 months. Four SMA patients (26.7%) had decreased sensory nerve action potentials (SNAPs) or sensory nerve conduction velocities. Of them, median SNAPs could not be elicited in 3, and sural SNAPs could not be elicited in 2. Compound muscle action potential amplitudes were severely decreased in 14 (93.3%) and normal in 1. Conclusions: Survival motor neuron 1 (SMN1) gene analysis should be considered if clinical features are consistent with SMA, even if pathological or electrophysiological findings demonstrate peripheral sensorimotor polyneuropathies. Muscle Nerve, 2013
Effective punching shear and moment capacity of flat plate-column connection with shear reinforcements for lateral loading
Authors: Song Jin-Kyu , Kim Jubum , Song Ho-Bum , Song Jeong-Won
Published: November 2012

In this study, three isolated interior flat slab-column connections that include three types of shear reinforcement details; stirrup, shear stud and shear band were tested under reversed cyclic lateral loading to observe the capacity of slab-column connections. These reinforced joints are 2/3 scale miniatures designed to have identical punching capacities. These experiments showed that the flexural failure mode appears in most specimens while the maximum unbalanced moment and energy absorbing capacity increases effectively, with the exception of an unreinforced standard specimen. Finally, the results of the experiments, as wel l as those of experiments previously carried out by researchers, are applied to the eccentricity shear stress model presented in ACI 318-08. The failure mode is therefore defined in this study by considering the upper limits for punching shear and unbalanced momen t. In addition, an intensity factor is proposed for effective widths of slabs that carry an unbalanced moment delivered by bending.
Homogenization of convex functionals which are weakly coercive and not equi-bounded from above
Authors: Briane Marc , Casado-Díaz Juan
Published: November 2012

This paper deals with the homogenization of nonlinear convex energies defined in

W_{0}^{1,1}(\Omega )

, for a regular bounded open set

Ω

of

\mathbb{R}^{N}

, the densities of which are not equi-bounded from above, and which satisfy the following weak coercivity condition: There exists

q > N−1

if

N > 2

, and

q⩾1

if

N = 2

, such that any sequence of bounded energy is compact in

W_{0}^{1,q}(\Omega )

. Under this assumption the

Γ

-convergence of the functionals for the strong topology of

L^{\infty }(\Omega )

is proved to agree with the

Γ

-convergence for the strong topology of

L^{1}(\Omega )

. This leads to an integral representation of the

Γ

-limit in

C_{0}^{1}(\Omega )

thanks to a local convex density. An example based on a thin cylinder with very low and very large energy densities, which concentrates to a line shows that the loss of the weak coercivity condition can induce nonlocal effects.
Characterization of the novel protein P9TLDR (temporal lobe down‐regulated) with a brain‐site‐specific gene expression modality in Alzheimer's disease brain
Authors: Yokota Tomoko , Akatsu Hiroyasu , Miyauchi Takashi , Heese Klaus
Published: November 2012

Alzheimer's disease (AD) is an aging‐related neurodegenerative disorder characterized by irreversible loss of higher cognitive functions. The disease is characterized by the presence of amyloid plaques and neurofibrillary tangles (NFT). In the current study we isolated from an intra‐cerebral brain‐site‐specific (AD temporal lobe vs. AD occipital lobe) polymerase chain reaction (PCR)‐select cDNA suppression subtractive hybridization (PCR‐cDNA‐SSH) expression analysis the novel gene P9TLDR, potentially a microtubule‐associated protein involved in neuronal migration, with an altered expression pattern: down‐regulated in the temporal lobe cortex of early stage AD brains. In an in vitro AD‐related cell model, amyloid‐β peptide (Aβ)‐treated neurons, reduced P9TLDR expression correlated with increased tau protein phosphorylation. In conclusion, interference with the P9TLDR signalling pathways might be a therapeutic strategy for the treatment of AD.
Wilderness Medical Society Practice Guidelines for Treatment of Eye Injuries and Illnesses in the Wilderness
Authors: Drake Brandy , Paterson Ryan , Tabin Geoffrey , Butler Frank K. , Cushing Tracy
Published: November 2012

A panel convened to develop an evidence-based set of guidelines for the recognition and treatment of eye injuries and illnesses that may occur in the wilderness. These guidelines are meant to serve as a tool to help wilderness providers accurately identify and subsequently treat or evacuate for a variety of ophthalmologic complaints. Recommendations are graded based on the quality of their supporting evidence and the balance between risks and benefits according to criteria developed by the American College of Chest Physicians.
CHANGING PERCEPTIONS OF WOMEN'S RELIGIOUS INSTITUTIONS IN EIGHTEENTH-CENTURY BOLOGNA
Authors: LEHTSALU LIISE
Published: November 2012

Eighteenth-century convents are little studied, and women's third order houses even less so, despite the growing numbers of the latter. Through a case-study, this article explores the origins and functions of one eighteenth-century third order house in an Italian urban community. Relying on the rich meeting minutes of Santa Maria Egiziaca in Bologna, the article analyses the everyday realities and the changing perceptions of women's religious institutions among the urban elites connected to the house. Santa Maria Egiziaca emerges as neither only a convent nor a shelter, the two institutional types recognized in current scholarship, but rather as both. The diverse goals of the house's administrators and benefactors suggest why third order houses thrived in the eighteenth century when more traditional convents came under increasing criticism and declined.
NEW PERSPECTIVES ON PIUS XII AND VATICAN FINANCIAL TRANSACTIONS DURING THE SECOND WORLD WAR
Authors: McGOLDRICK PATRICIA M.
Published: November 2012

The debate about the political allegiance of Pius XII and the Vatican during the Second World War remains unresolved. As more documents become available, they enable historians, detractors and defenders alike, to develop a more nuanced view on this contentious issue. Files recently released by The National Archives1 come within this category. They reveal that during the Second World War the British government systematically intercepted, monitored, and recorded in detail the financial transactions listed in the bank statements of the main financial agencies of the State of Vatican City from 1941 to 1943. These documents provide a detailed, if occasionally incomplete, day by day and month by month record of the Vatican's sources of income, expenditure priorities, investment strategies, and movements of money throughout its global network under the difficult wartime conditions of foreign exchange controls, blocked sterling and dollar accounts, Freezing Orders, and Trading with the Enemy restrictions imposed by the belligerent parties. This article examines the light they shed on Vatican finances throughout that period and what new insights they provide into the role of Pius XII and the Vatican during the Second World War, and, in particular, into the question of where their sympathies lay throughout the duration of that conflict.
How vegetables make the meal: their hedonic and heroic impact on perceptions of the meal and of the preparer
Authors: Wansink Brian , Shimizu Mitsuru , Brumberg Adam
Published: November 2012

Objective

Although most parents know that vegetables are healthful, vegetables are served at only 23 % of American dinners. If added nutrition is not a sufficient motivation, might a parent be more inspired to serve vegetables if doing so improved either the taste of the entrée or how loving and thoughtful the server would be perceived? The present paper details two studies which investigated whether serving vegetables changes the perception of the cook and the perception of an entrée's taste.

Design

In Study 1, people evaluated the personality of a cook who either did or did not include a vegetable in a family dinner. In Study 2, five different meals that either included or did not include a vegetable were rated in terms of the taste of the entrée and of the whole meal.

Setting

US-based online survey.

Subjects

American mothers (n 500), ranging in age from 18 to 65 years (mean age 38·4 years), with at least two children under the age of 18 years living at home.

Results

Serving vegetables improved taste expectations for the entrée as well as for the whole meal. Additionally, serving a vegetable with a meal also enhanced perceptions of the meal preparer. They were evaluated as being more thoughtful and attentive as well as less lazy, boring and self-absorbed.

Conclusions

These two studies show new hedonic and heroic motivations for serving vegetables: (i) they increase the hedonic appeal of the meal and (ii) they increase the heroic appeal of the cook. More vegetables are likely to be served with a meal if preparers know that the addition of vegetables makes them appear to be both a better cook and a better person.
Generalized likelihood uncertainty estimation (GLUE) and approximate Bayesian computation: What's the connection?
Authors: Nott David J. , Marshall Lucy , Brown Jason
Published: November 2012

There has been a recent debate in the hydrological community about the relative merits of the informal generalized likelihood uncertainty estimation (GLUE) approach to uncertainty assessment in hydrological modeling versus formal probabilistic approaches. Some recent literature has suggested that the methods can give similar results in practice when properly applied. In this note, we show that the connection between formal Bayes and GLUE is not merely operational but goes deeper, with GLUE corresponding to a certain approximate Bayesian procedure even when the “generalized likelihood” is not a true likelihood. The connection we describe relates to recent approximate Bayesian computation (ABC) methods originating in genetics. ABC algorithms involve the use of a kernel function, and the generalized likelihood in GLUE can be thought of as relating to this kernel function rather than to the model likelihood. Two interpretations of GLUE emerge, one as a computational approximation to a Bayes procedure for a certain “error‐free” model and the second as an exact Bayes procedure for a perturbation of that model in which the truncation of the generalized likelihood in GLUE plays a role. The intent of this study is to encourage cross‐fertilization of ideas regarding GLUE and ABC in hydrologic applications. The connection we outline suggests the possibility of combining a formal likelihood with a kernel based on a generalized likelihood within the ABC framework and also allows advanced ABC computational methods to be used in GLUE applications. The model‐based interpretation of GLUE may also be helpful in partially illuminating the implicit assumptions in different choices of generalized likelihood.
Spontaneous hot flow anomalies at quasi‐parallel shocks: 2. Hybrid simulations
Authors: Omidi N. , Zhang H. , Sibeck D. , Turner D.
Published: November 2012

Motivated by recent THEMIS observations, this paper uses 2.5‐D electromagnetic hybrid simulations to investigate the formation of Spontaneous Hot Flow Anomalies (SHFAs) upstream of quasi‐parallel bow shocks during steady solar wind conditions and in the absence of discontinuities. The results show the formation of a large number of structures along and upstream of the quasi‐parallel bow shock. Their outer edges exhibit density and magnetic field enhancements, while their cores exhibit drops in density, magnetic field, solar wind velocity, and enhancements in ion temperature. Using virtual spacecraft in the simulation, we show that the signatures of these structures in the time series data are very similar to those of SHFAs seen in THEMIS data and conclude that they correspond to SHFAs. Examination of the simulation data shows that SHFAs form as the result of foreshock cavitons interacting with the bow shock. Foreshock cavitons in turn form due to the nonlinear evolution of ULF waves generated by the interaction of the solar wind with the backstreaming ions. Because foreshock cavitons are an inherent part of the shock dissipation process, the formation of SHFAs is also an inherent part of the dissipation process leading to a highly nonuniform plasma in the quasi‐parallel magnetosheath including large‐scale density and magnetic field cavities.
Analytical solutions and numerical tests of elastic and failure behaviors of close‐packed lattice for brittle rocks and crystals
Authors: Liu Chun , Pollard David D. , Shi Bin
Published: November 2012

Analytical solutions of elastic properties and failure modes of a two‐dimensional close‐packed discrete element model are proposed. Based on the assumption of small deformation, the conversion formulas between five inter‐particle parameters of the lattice model and rock mechanical properties were derived. Using the formulas, the inter‐particle parameters can be determined by Young's modulus (E), Poisson's ratio (v), tensile strength (Tu), compressive strength (Cu), and coefficient of intrinsic friction (μi). The lattice defined by the parameters simulates the elastic and failure behaviors of rocks and crystals and therefore can be used to investigate the initiation and development of geological structures quantitatively. Furthermore, the solutions also provide a theoretical basis for the calibration of parameters of random discrete assemblies. The model of quartz was used as an example to validate the formulas and test the errors. The simulated results show that E and v converge to theoretical values when particle number increases. These elastic properties are almost constant when the magnitude of strain is lower than 10−3. The simulated Tu and Cu of a single three‐element unit are also consistent with the formulas. However, due to the boundary effects and stress concentrations, Tu and Cu of lattices with multiple units are lower than the values predicted by the formulas. Therefore, greater Tu and Cu can be used in the formulas to counteract this effect. The model is applicable to the simulation of complicated structures that involve deformation and failure at different scales.
Uncertainty quantification and parameter tuning in the CAM5 Zhang‐McFarlane convection scheme and impact of improved convection on the global circulation and climate
Authors: Yang Ben , Qian Yun , Lin Guang , Leung L. Ruby , Rasch Philip J. , Zhang Guang J. , McFarlane Sally A. , Zhao Chun , Zhang Yaocun , Wang Hailong , Wang Minghuai , Liu Xiaohong
Published: November 2012

In this study, we applied an uncertainty quantification (UQ) technique to improve convective precipitation in the global climate model, the Community Atmosphere Model version 5 (CAM5), in which the convective and stratiform precipitation partitioning is very different from observational estimates. We examined the sensitivity of precipitation and circulation to several key parameters in the Zhang‐McFarlane deep convection scheme in CAM5, using a stochastic importance‐sampling algorithm that can progressively converge to optimal parameter values. The impact of improved deep convection on the global circulation and climate was subsequently evaluated. Our results show that the simulated convective precipitation is most sensitive to the parameters of the convective available potential energy consumption time scale, parcel fractional mass entrainment rate, and maximum downdraft mass flux fraction. Using the optimal parameters constrained by the observed Tropical Rainfall Measuring Mission, convective precipitation improves the simulation of convective to stratiform precipitation ratio and rain‐rate spectrum remarkably. When convection is suppressed, precipitation tends to be more confined to the regions with strong atmospheric convergence. As the optimal parameters are used, positive impacts on some aspects of the atmospheric circulation and climate, including reduction of the double Intertropical Convergence Zone, improved East Asian monsoon precipitation, and improved annual cycles of the cross‐equatorial jets, are found as a result of the vertical and horizontal redistribution of latent heat release from the revised parameterization. Positive impacts of the optimal parameters derived from the 2° simulations are found to transfer to the 1° simulations to some extent.
Is eastern Mongolia drying? A long‐term perspective of a multidecadal trend
Authors: Davi Nicole K. , Pederson Neil , Leland Caroline , Nachin Baatarbileg , Suran Byambagerel , Jacoby Gordon C.
Published: November 2012

Key Points

Significantly spatially and temporally improved streamflow reconstruction

Greater variability captured then in the original reconstruction

Drought conditions seen over the past decade may be return to normal conditions
Strain-specific functional and numerical responses are required to evaluate impacts on predator–prey dynamics
Authors: Yang Zhou , Lowe Chris D , Crowther Will , Fenton Andy , Watts Phillip C , Montagnes David J S
Published: November 2012

We use strains recently collected from the field to establish cultures; then, through laboratory studies we investigate how among strain variation in protozoan ingestion and growth rates influences population dynamics and intraspecific competition. We focused on the impact of changing temperature because of its well-established effects on protozoan rates and its ecological relevance, from daily fluctuations to climate change. We show, first, that there is considerable inter-strain variability in thermal sensitivity of maximum growth rate, revealing distinct differences among multiple strains of our model species Oxyrrhis marina. We then intensively examined two representative strains that exhibit distinctly different thermal responses and parameterised the influence of temperature on their functional and numerical responses. Finally, we assessed how these responses alter predator–prey population dynamics. We do this first considering a standard approach, which assumes that functional and numerical responses are directly coupled, and then compare these results with a novel framework that incorporates both functional and numerical responses in a fully parameterised model. We conclude that: (i) including functional diversity of protozoa at the sub-species level will alter model predictions and (ii) including directly measured, independent functional and numerical responses in a model can provide a more realistic account of predator–prey dynamics.
The unaccounted yet abundant nitrous oxide-reducing microbial community: a potential nitrous oxide sink
Authors: Jones Christopher M , Graf Daniel R H , Bru David , Philippot Laurent , Hallin Sara
Published: November 2012

Nitrous oxide (N2O) is a major radiative forcing and stratospheric ozone-depleting gas emitted from terrestrial and aquatic ecosystems. It can be transformed to nitrogen gas (N2) by bacteria and archaea harboring the N2O reductase (N2OR), which is the only known N2O sink in the biosphere. Despite its crucial role in mitigating N2O emissions, knowledge of the N2OR in the environment remains limited. Here, we report a comprehensive phylogenetic analysis of the nosZ gene coding the N2OR in genomes retrieved from public databases. The resulting phylogeny revealed two distinct clades of nosZ, with one unaccounted for in studies investigating N2O-reducing communities. Examination of N2OR structural elements not considered in the phylogeny revealed that the two clades differ in their signal peptides, indicating differences in the translocation pathway of the N2OR across the membrane. Sequencing of environmental clones of the previously undetected nosZ lineage in various environments showed that it is widespread and diverse. Using quantitative PCR, we demonstrate that this clade was most often at least as abundant as the other, thereby more than doubling the known extent of the overall N2O-reducing community in the environment. Furthermore, we observed that the relative abundance of nosZ from either clade varied among habitat types and environmental conditions. Our results indicate a physiological dichotomy in the diversity of N2O-reducing microorganisms, which might be of importance for understanding the relationship between the diversity of N2O-reducing microorganisms and N2O reduction in different ecosystems.
The DNA virus Invertebrate iridescent virus 6 is a target of the
Drosophila
RNAi machinery
Authors: Bronkhorst Alfred W. , van Cleef Koen W. R. , Vodovar Nicolas , İnce İkbal Agah , Blanc Hervé , Vlak Just M. , Saleh Maria-Carla , van Rij Ronald P.
Published: November 2012

RNA viruses in insects are targets of an RNA interference (RNAi)-based antiviral immune response, in which viral replication intermediates or viral dsRNA genomes are processed by Dicer-2 (Dcr-2) into viral small interfering RNAs (vsiRNAs). Whether dsDNA virus infections are controlled by the RNAi pathway remains to be determined. Here, we analyzed the role of RNAi in DNA virus infection using
Drosophila melanogaster
infected with Invertebrate iridescent virus 6 (IIV-6) as a model. We show that
Dcr-2
and
Argonaute-2
mutant flies are more sensitive to virus infection, suggesting that vsiRNAs contribute to the control of DNA virus infection. Indeed, small RNA sequencing of IIV-6–infected WT and RNAi mutant flies identified abundant vsiRNAs that were produced in a
Dcr-2
–dependent manner. We observed a highly uneven distribution with strong clustering of vsiRNAs to small defined regions (hotspots) and modest coverage at other regions (coldspots). vsiRNAs mapped in similar proportions to both strands of the viral genome, suggesting that long dsRNA derived from convergent overlapping transcripts serves as a substrate for Dcr-2. In agreement, strand-specific RT-PCR and Northern blot analyses indicated that antisense transcripts are produced during infection. Moreover, we show that vsiRNAs are functional in silencing reporter constructs carrying fragments of the IIV-6 genome. Together, our data indicate that RNAi provides antiviral defense against dsDNA viruses in animals. Thus, RNAi is the predominant antiviral defense mechanism in insects that provides protection against all major classes of viruses.
SmgGDS antagonizes BPGAP1-induced Ras/ERK activation and neuritogenesis in PC12 cell differentiation
Authors: Ravichandran Aarthi , Low Boon Chuan
Published: November 2012

BPGAP1 is a Rho GTPase-activating protein (RhoGAP) that regulates cell morphogenesis, cell migration, and ERK signaling by the concerted action of its proline-rich region (PRR), RhoGAP domain, and the BNIP-2 and Cdc42GAP homology (BCH) domain. Although multiple cellular targets for the PRR and RhoGAP have been identified, and their functions delineated, the mechanism by which the BCH domain regulates functions of BPGAP1 remains unclear. Here we show that its BCH domain induced robust ERK activation leading to PC12 cell differentiation by targeting specifically to K-Ras. Such stimulatory effect was inhibited, however, by both dominant-negative mutants of Mek2 (Mek2-K101A) and K-Ras (K-Ras-S17N) and also by the small G-protein GDP dissociation stimulator (SmgGDS). Consequently SmgGDS knockdown released this inhibition and resulted in a superinduction of K-Ras activation and PC12 differentiation mediated by BCH domain. These results demonstrate the versatility of the BCH domain of BPGAP1 in regulating ERK signaling by involving K-Ras and SmgGDS and support the unique role of BPGAP1 as a dual regulator for Ras and Rho signaling in cell morphogenesis and differentiation.
Effects of Tat proteins and Tat mutants of different human immunodeficiency virus type 1 clades on glial JC virus early and late gene transcription
Authors: Wright Clayton A. , Nance Jonas A. , Johnson Edward M.
Published: November 2012

Polyomavirus JC (JCV) is the aetiological agent of progressive multifocal leukoencephalopathy (PML), a frequently fatal infection of the brain afflicting nearly 4 % of AIDS patients in the USA. Human immunodeficiency virus type 1 (HIV-1) Tat, acting together with cellular proteins at the JCV non-coding control region (NCCR), can stimulate JCV DNA transcription and replication. Tat in the brain is secreted by HIV-1-infected cells and incorporated by oligodendroglia, cells capable of infection by JCV. Thus far the effects of Tat on JCV have been studied primarily with protein encoded by the HIV-1 B clade most common in North America. Here, we determine the abilities of Tat from different HIV-1 clades to alter JCV early and late gene transcription and DNA replication initiated at the JCV origin. Tat from all clades tested stimulates both JCV early and late gene promoters, with clade B Tat being significantly most effective. Tat proteins from the HIV-1 clades display parallel patterns of differences in their effects on HIV-1 and JCV transcription, suggesting that Tat effects in both cases are mediated by the same cellular proteins. Clade B Tat is most effective at directing Smad mediators of tumour growth factor beta and cellular partner Purα to the NCCR. Tat proteins from all non-B clades inhibit initiation of JCV DNA replication. The effectiveness of HIV-1 clade B Tat at promoting JCV transcriptional and replicative processes highlights a need for further investigation to determine which molecular aspects of Tat from distinct HIV-1 substrains can contribute to the course of PML development in neuroAIDS.
The SMAD2/3 corepressor SNON maintains pluripotency through selective repression of mesendodermal genes in human ES cells
Authors: Tsuneyoshi Norihiro , Tan Ee Kim , Sadasivam Akila , Poobalan Yogavalli , Sumi Tomoyuki , Nakatsuji Norio , Suemori Hirofumi , Dunn N. Ray
Published: November 2012

Activin/Nodal signaling via SMAD2/3 maintains human embryonic stem cell (hESC) pluripotency by direct transcriptional regulation of NANOG or, alternatively, induces mesoderm and definitive endoderm (DE) formation. In search of an explanation for these contrasting effects, we focused on SNON (SKIL), a potent SMAD2/3 corepressor that is expressed in hESCs but rapidly down-regulated upon differentiation. We show that SNON predominantly associates with SMAD2 at the promoters of primitive streak (PS) and early DE marker genes. Knockdown of SNON results in premature activation of PS and DE genes and loss of hESC morphology. In contrast, enforced SNON expression inhibits DE formation and diverts hESCs toward an extraembryonic fate. Thus, our findings provide novel mechanistic insight into how a single signaling pathway both regulates pluripotency and directs lineage commitment.
Thioredoxin m4 Controls Photosynthetic Alternative Electron Pathways in Arabidopsis
Authors: Courteille Agathe , Vesa Simona , Sanz-Barrio Ruth , Cazalé Anne-Claire , Becuwe-Linka Noëlle , Farran Immaculada , Havaux Michel , Rey Pascal , Rumeau Dominique
Published: November 2012

In addition to the linear electron flow, a cyclic electron flow (CEF) around photosystem I occurs in chloroplasts. In CEF, electrons flow back from the donor site of photosystem I to the plastoquinone pool via two main routes: one that involves the Proton Gradient Regulation5 (PGR5)/PGRL1 complex (PGR) and one that is dependent of the NADH dehydrogenase-like complex. While the importance of CEF in photosynthesis and photoprotection has been clearly established, little is known about its regulation. We worked on the assumption of a redox regulation and surveyed the putative role of chloroplastic thioredoxins (TRX). Using Arabidopsis (Arabidopsis thaliana) mutants lacking different TRX isoforms, we demonstrated in vivo that TRXm4 specifically plays a role in the down-regulation of the NADH dehydrogenase-like complex-dependent plastoquinone reduction pathway. This result was confirmed in tobacco (Nicotiana tabacum) plants overexpressing the TRXm4 orthologous gene. In vitro assays performed with isolated chloroplasts and purified TRXm4 indicated that TRXm4 negatively controls the PGR pathway as well. The physiological significance of this regulation was investigated under steady-state photosynthesis and in the pgr5 mutant background. Lack of TRXm4 reversed the growth phenotype of the pgr5 mutant, but it did not compensate for the impaired photosynthesis and photoinhibition sensitivity. This suggests that the physiological role of TRXm4 occurs in vivo via a mechanism distinct from direct up-regulation of CEF.
Quantitative analysis of turbostratically disordered nontronite with a supercell model calibrated by the PONKCS method
Authors: Wang Xiaodong , Hart Robert D. , Li Jian , McDonald Robbie G. , van Riessen Arie
Published: November 2012

Two calibration-based quantitative X-ray diffraction (XRD) models for turbostratically disordered Bulong nontronite, the PONKCS (partial or no known crystal structure) approach and the supercell structural model, were compared in terms of the accuracy and refinement error from Rietveld quantitative phase analysis. The PONKCS approach achieved improved nontronite quantitative results with synchrotron diffraction patterns compared with those achieved with laboratory XRD data as a result of better data quality and the use of Debye–Scherrer geometry with significantly reduced preferred orientation effects. The introduction of a peak shape modifier (spherical harmonics) to correct the quantification result is mainly useful for laboratory XRD patterns containing nontronite collected from Bragg–Brentano geometry with appreciable preferred orientation effects. A novel calibration approach for the nontronite supercell model was developed, based on the Rietveld quantitative formula in theTOPASsymbolic computation system. The calibrated supercell model achieved better accuracy (deviation within 1 wt%) and lower refinement error than the PONKCS approach because the physically based description of turbostratic disorder requires fewer refinable parameters than the PONKCS approach. The drawbacks and limitations of the supercell approach are also discussed.
Diffraction/scattering computed tomography for three-dimensional characterization of multi-phase crystalline and amorphous materials
Authors: Álvarez-Murga M. , Bleuet P. , Hodeau J.-L.
Published: November 2012

The three-dimensional characterization method described herein is based on diffraction and scattering techniques combined with tomography and uses the variation of these signals to reconstruct a two-dimensional/three-dimensional structural image. To emphasize the capability of the method in discriminating between different poorly ordered phases, it is named diffraction/scattering computed tomography (DSCT). This combination not only allows structural imaging but also yields an enhancement of the weak signals coming from minor phases, thereby increasing the sensitivity of structural probes. This article reports the suitability of the method for discrimination of polycrystalline and amorphous phases and for extraction of their selective local patterns with a contrast sensitivity of about 0.1% in weight of minor phases relative to the matrix. The required background in tomography is given and then the selectivity of scattering signal, the efficiency of the method, reconstruction artefacts and limitations are addressed. The approach is illustrated through different examples covering a large range of applications based on recent literature, showing the potential of DSCT in crystallography and materials science, particularly when functional and/or precious samples with sub-micrometre features have to be investigated in a nondestructive way.
VLD algorithm and hybrid Fourier syntheses
Authors: Burla Maria Cristina , Carrozzini Benedetta , Cascarano Giovanni Luca , Giacovazzo Carmelo , Polidori Giampiero
Published: November 2012

The VLD (vive la difference) phasing algorithm combines the model electron density with the difference electron densityviareciprocal space relationships to obtain new phase values and drive them to the correct values. The process is iterative and has been applied to small and medium-size structures and to proteins. Hybrid Fourier syntheses show properties that are intermediate between those of the observed synthesis (whose peaks should correspond to the most probable atomic positions) and those of the difference synthesis (whose positive and negative peaks should correspond to missed atomic positions and to false atoms of the model, respectively). Thanks to these properties some hybrid syntheses can be used in the phase extension and refinement step, to reduce the model bias and more rapidly move to the target structure. They have been recently revisitedviathe method of joint probability distribution functions [Burla, Carrozzini, Cascarano, Giacovazzo & Polidori (2011).Acta. Cryst. A67, 447–455]. The results suggested that VLD could be usefully combined, forab initiophasing, with the hybrid rather than with the difference Fourier synthesis. This paper explores the feasibility of such a combination and shows that the original VLD algorithm is only one of several variants, all with relevant phasing capacity. The study explores the role of several parameters in order to design a standard procedure with optimized phasing power.
Magnetic symmetry in the Bilbao Crystallographic Server: a computer program to provide systematic absences of magnetic neutron diffraction
Authors: Gallego Samuel V. , Tasci Emre S. , de la Flor Gemma , Perez-Mato J. Manuel , Aroyo Mois I.
Published: November 2012

MAGNEXTis a new computer program available from the Bilbao Crystallographic Server (http://www.cryst.ehu.es) that provides symmetry-forced systematic absences or extinction rules of magnetic nonpolarized neutron diffraction. For any chosen Shubnikov magnetic space group, the program lists all systematic absences, and it can also be used to obtain the list of the magnetic space groups compatible with a particular set of observed systematic absences. Absences corresponding to specific ordering modes can be derived by introducing effective symmetry operations associated with them. Although systematic extinctions in neutron diffraction do not possess the strong symmetry-resolving power of those in nonmagnetic crystallography, they can be important for the determination of some magnetic structures. In addition,MAGNEXTprovides the symmetry-adapted form of the magnetic structure factor for different types of diffraction vectors, which can then be used to predict additional extinctions caused by some prevailing orientation of the atomic magnetic moments. This program, together with a database containing comprehensive general information on the symmetry operations and the Wyckoff positions of the 1651 magnetic space groups, is the starting point of a new section in the Bilbao Crystallographic Server devoted to magnetic symmetry and its applications.
Diabetic retinopathy in patients with newly diagnosed type 2 diabetes mellitus in Jordan: Prevalence and associated factors (约旦新诊断2型糖尿病患者的糖尿病视网膜病变：患病率与相关因素)
Authors: Jammal Hisham , Khader Yousef , Alkhatib Shadi , Abujbara Mousa , Alomari Mousa , Ajlouni Kamel
Published: November 2012

Background

To determine the prevalence of diabetic retinopathy (DR) in patients with newly diagnosed type 2 diabetes mellitus (T2DM) in Jordan, as well as the factors associated with DR.

Methods

A cross‐sectional study was conducted among 127 consecutive newly diagnosed (within the past 6 months) patients with T2DM attending one of two diabetic care centers. Complete ocular examinations were performed by an ophthalmologist and relevant data were collected. A fundus examination was performed using slit lamp indirect ophthalmoscopy after pupillary dilation with 1% tropicamide drops, with DR defined and classified according to the scale developed by the Global Diabetic Retinopathy Project Group.

Results

Of all the patients examined, 7.9% had DR. Of those with DR, 40% already had clinically significant macular edema necessitating laser photocoagulation or intravitreal injections. Multivariate analysis revealed that age and HbA1c were significantly associated with DR. The odds of DR increased by 11% for each 1 year increase in age (odds ratio [OR] 1.11; 95% confidence interval [CI] 1.02–1.20). For each 1% increase in HbA1c, the odds of DR increased by 43% (OR 1.43; 95% CI 1.09–1.88).

Conclusions

Fewer than one‐tenth of newly diagnosed Jordanian patients with T2DM had DR, but more than one‐third of these patients had significant maculopathy. Therefore, early screening is strongly recommended for all newly diagnosed T2DM patients. Increased age and HbA1c values are associated with increased odds of DR. A study with a larger sample size is needed to elucidate the risk factors for DR in newly diagnosed T2DM.
Response assessment in Waldenström macroglobulinaemia: update from the VIth International Workshop
Authors: Owen Roger G. , Kyle Robert A. , Stone Marvin J. , Rawstron Andy C. , Leblond Veronique , Merlini Giampaolo , Garcia‐Sanz Ramon , Ocio Enrique M. , Morra Enrica , Morel Pierre , Anderson Kenneth C. , Patterson Christopher J. , Munshi Nikhil C. , Tedeschi Alessandra , Joshua Douglas E. , Kastritis Efstathios , Terpos Evangelos , Ghobrial Irene M. , Leleu Xavier , Gertz Morie A. , Ansell Stephen M. , Morice William G. , Kimby Eva , Treon Steven P.
Published: November 2012

This report represents a further update of the consensus panel criteria for the assessment of clinical response in patients with Waldenström macroglobulinaemia (WM). These criteria have been updated in light of further data demonstrating an improvement in categorical responses with new drug regimens as well as acknowledgement of the fact that such responses are predictive of overall outcome. A number of key changes are proposed but challenges do however remain and these include the variability in kinetics of immunoglobulin M (IgM) reduction with different treatment modalities and the apparent discrepancy between IgM and bone marrow/tissue response noted with some regimens. Planned sequential bone marrow assessments are encouraged in clinical trials.
JAK2‐V617F‐mediated signalling is dependent on lipid rafts and statins inhibit JAK2‐V617F‐dependent cell growth
Authors: Griner Lori N. , McGraw Kathy L. , Johnson Joseph O. , List Alan F. , Reuther Gary W.
Published: November 2012

Aberrant JAK2 signalling plays an important role in the aetiology of myeloproliferative neoplasms (MPNs). JAK2 inhibitors, however, do not readily eliminate neoplastic MPN cells and thus do not induce patient remission. Further understanding JAK2 signalling in MPNs may uncover novel avenues for therapeutic intervention. Recent work has suggested a potential role for cellular cholesterol in the activation of JAK2 by the erythropoietin receptor and in the development of an MPN‐like disorder in mice. Our study demonstrates for the first time that the MPN‐associated JAK2‐V617F kinase localizes to lipid rafts and that JAK2‐V617F‐dependent signalling is inhibited by lipid raft disrupting agents, which target membrane cholesterol, a critical component of rafts. We also show for the first time that statins, 3‐hydroxy‐3‐methyl‐glutaryl coenzyme A (HMG‐CoA) reductase inhibitors, widely used to treat hypercholesterolaemia, induce apoptosis and inhibit JAK2‐V617F‐dependent cell growth. These cells are more sensitive to statin treatment than non‐JAK2‐V617F‐dependent cells. Importantly, statin treatment inhibited erythropoietin‐independent erythroid colony formation of primary cells from MPN patients, but had no effect on erythroid colony formation from healthy individuals. Our study is the first to demonstrate that JAK2‐V617F signalling is dependent on lipid rafts and that statins may be effective in a potential therapeutic approach for MPNs.
What is the best diagnostic and therapeutic management strategy for an Addison patient during pregnancy?
Authors: Lebbe Marie , Arlt Wiebke
Published: November 2012

A new diagnosis of primary adrenal insufficiency (PAI) during pregnancy is extremely rare and difficult to recognize as signs and symptoms such as nausea, fatigue and hypotension may resemble features of normal pregnancy. However, if the diagnosis is overlooked and steroid replacement delayed, subsequent adrenal crisis triggered by hyperemesis gravidarum, fever or delivery can cause severe maternal and foetal morbidity and even mortality. In case of clinical suspicion of PAI, we recommend to measure paired samples of cortisol and ACTH and, if clinically feasible, a short synacthen test. We propose trimester‐specific pass cut‐offs for the short synacthen test that take into account the rise of total and also free cortisol during pregnancy. Empirical hydrocortisone treatment should never be delayed if the clinical suspicion is high. All pregnant women with PAI should be monitored by a team of endocrine and obstetric specialists. The third trimester is physiologically associated with a rise not only in total but also free cortisol and thus requires regular adjustment of the glucocorticoid dose. Mineralocorticoid requirements may change during pregnancy due to the anti‐mineralocorticoid properties of progesterone. As plasma renin physiologically increases in pregnancy, monitoring is limited to clinical assessment including blood pressure and serum electrolytes. It is crucial that a pregnant woman with PAI and her partner are well educated regarding the adjustment of glucocorticoid dose in intercurrent illness and that both are trained in hydrocortisone emergency injection techniques. The obstetric staff should be provided with clear and written guidance for hydrocortisone cover during labour and delivery. With the appropriate replacement therapy, PAI patients can expect to have an uneventful pregnancy and deliver a healthy infant.