bluuebunny/crossref_metadata_2025 huggingface dataset:
The 5′ Untranslated Region of the Human T-Cell Lymphotropic Virus Type 1 mRNA Enables Cap-Independent Translation Initiation
Authors: Olivares Eduardo , Landry Dori M. , Cáceres C. Joaquín , Pino Karla , Rossi Federico , Navarrete Camilo , Huidobro-Toro Juan Pablo , Thompson Sunnie R. , López-Lastra Marcelo
Published: March 2014

The human T-cell leukemia virus type 1 (HTLV-1) is a complex human retrovirus that causes adult T cell leukemia and of HTLV-associated myelopathy/tropical spastic paraparesis. The mRNA of some complex retroviruses, including the human and simian immunodeficiency viruses (HIV and SIV), can initiate translation using a canonical cap-dependent mechanism or through an internal ribosome entry site (IRES). In this study, we present strong evidence showing that like HIV-1 and SIV, the 5′-untranslated region (5′UTR) of the HTLV-1 full-length mRNA harbors an IRES. Cap-independent translational activity was evaluated and demonstrated using dual luciferase bicistronic mRNAs in rabbit reticulocyte lysate, in mammalian cell culture, and in
Xenopus laevis
oocytes. Characterization of the HTLV-1 IRES shows that its activity is dependent on the ribosomal protein S25 (RPS25) and that its function is highly sensitive to the drug edeine. Together, these findings suggest that the 5′UTR of the HTLV-1 full-length mRNA enables internal recruitment of the eukaryotic translation initiation complex. However, the recognition of the initiation codon requires ribosome scanning. These results suggest that, after internal recruitment by the HTLV-1 IRES, a scanning step takes place for the 40S ribosomal subunit to be positioned at the translation initiation codon.

IMPORTANCE
The mechanism by which retroviral mRNAs recruit the 40S ribosomal subunit internally is not understood. This study provides new insights into the mechanism of translation initiation used by the human T-cell lymphotropic virus type 1 (HTLV-1). The results show that the HTLV-1 mRNA can initiate translation via a noncanonical mechanism mediated by an internal ribosome entry site (IRES). This study also provides evidence showing the involvement of cellular proteins in HTLV-1 IRES-mediated translation initiation. Together, the data presented in this report significantly contribute to the understanding of HTLV-1 gene expression.
Conserved Features of the PB2 627 Domain Impact Influenza Virus Polymerase Function and Replication
Authors: Kirui James , Bucci Michael D. , Poole Daniel S. , Mehle Andrew
Published: March 2014

Successful replication of influenza virus requires the coordinated expression of viral genes and replication of the genome by the viral polymerase, composed of the subunits PA, PB1, and PB2. Polymerase activity is regulated by both viral and host factors, yet the mechanisms of regulation and how they contribute to viral pathogenicity and tropism are poorly understood. To characterize these processes, we created a series of mutants in the 627 domain of the PB2 subunit. This domain contains a conserved “P[F/P]AAAPP” sequence motif and the well-described amino acid 627, whose identity regulates host range. A lysine present at position 627 in most mammalian viral isolates creates a basic face on the domain surface and confers high-level activity in humans compared to the glutamic acid found at this position in avian isolates. Mutation of the basic face or the P[F/P]AAAPP motif impaired polymerase activity, assembly of replication complexes, and viral replication. Most of these residues are required for general polymerase activity, whereas PB2 K586 and R589 were preferentially required for function in human versus avian cells. Thus, these data identify residues in the 627 domain and other viral proteins that regulate polymerase activity, highlighting the importance of the surface charge and structure of this domain for virus replication and host adaptation.

IMPORTANCE
Influenza virus faces barriers to transmission across species as it emerges from its natural reservoir in birds to infect mammals. The viral polymerase is an important regulator of this process and undergoes discrete changes to adapt to replication in mammals. Many of these changes occur in the polymerase subunit PB2. Here we describe the systematic analysis of a key region in PB2 that controls species-specific polymerase activity. We report the importance of conserved residues that contribute to the overall charge of the protein as well as those that likely affect protein structure. These findings provide further insight into the molecular events dictating species-specific polymerase function and viral replication.
Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1 Matrix Proteins Specify Different Capabilities To Modulate B Cell Growth
Authors: Caccuri Francesca , Giagulli Cinzia , Reichelt Joachim , Martorelli Debora , Marsico Stefania , Bugatti Antonella , Barone Ines , Rusnati Marco , Guzman Carlos A. , Dolcetti Riccardo , Caruso Arnaldo
Published: March 2014

Exogenous HIV-1 matrix protein p17 (p17) deregulates the function of different cells after its N-terminal loop (AT20) binding to the chemokine receptors CXCR1 and CXCR2. One site within AT20 has been recently found to be the major determinant of viral fitness following transmission of simian immunodeficiency virus (SIV) to the human host. Therefore, we sought to determine whether SIV matrix protein (MA) was already capable of interacting with CXCR1 and CXCR2 and mimic p17 biological activities rather than this being a newly acquired function during host adaptation. We show here that SIV MA binds with the same affinity of p17 to CXCR1 and CXCR2 and displays both p17 proangiogenic on human primary endothelial cells and chemotactic activity on human primary monocytes and B cells. However, SIV MA exhibited a higher degree of plasticity than p17 in the C terminus, a region known to play a role in modulating B cell growth. Indeed, in contrast to p17, SIV MA was found to activate the phosphatidylinositol 3-kinase/Akt signaling pathway and strongly promote B cell proliferation and clonogenic activity. Interestingly, we have recently highlighted the existence of a Ugandan HIV-1 strain-derived p17 variant (S75X) with the same B cell growth-promoting activity of SIV MA. Computational modeling allowed us to hypothesize an altered C terminus/core region interaction behind SIV MA and S75X activity. Our findings suggest the appearance of a structural constraint in the p17 C terminus that controls B cell growth, which may help to elucidate the evolutionary trajectory of HIV-1.

IMPORTANCEThe HIV-1 matrix protein p17 (p17) deregulates the biological activities of different cells after binding to the chemokine receptors CXCR1 and CXCR2. The p17 functional domain responsible for receptors interaction includes an amino acid which is considered the major determinant of SIV replication in humans. Therefore, we sought to determine whether SIV matrix protein (SIV MA) already had the ability to bind to both chemokine receptors rather than being a function newly acquired during host adaptation. We show here that SIV MA binds to CXCR1 and CXCR2 and fully mimics the p17 proangiogenic and chemokine activity. However, it differs from p17 in its ability to signal into B cells and promote B cell growth and clonogenicity. Computational analysis suggests that the accumulation of mutations in the C-terminal region may have led to a further SIV MA adaptation to the human host. This finding in turn sheds light on the evolutionary trajectory of HIV-1.
Dengue Virus- and Hepatitis C Virus-Induced Replication and Assembly Compartments: the Enemy Inside—Caught in the Web
Authors: Chatel-Chaix Laurent , Bartenschlager Ralf
Published: March 2014

Dengue virus (DENV) and hepatitis C virus (HCV), members of the family
Flaviviridae
, are global human health concerns. As positive-strand RNA viruses, they each replicate in the cytoplasm of infected cells and induce distinct membranous replication compartments where most, if not all, steps of the viral life cycle occur. This Gem briefly reviews the most recent insights into the architecture and functional properties of membranous replication and assembly sites induced by DENV and HCV.
Bona Fide Evidence for Natural Vertical Transmission of Infectious Salmon Anemia Virus in Freshwater Brood Stocks of Farmed Atlantic Salmon (Salmo salar) in Southern Chile
Authors: Marshall Sergio H. , Ramírez Ramón , Labra Alvaro , Carmona Marisela , Muñoz Cristián
Published: March 2014

Infectious salmon anemia (ISA) is a severe disease that affects farmed Atlantic salmon (
Salmo salar
), causing outbreaks in seawater in most salmon-producing countries worldwide, with particular aggressiveness in southern Chile. The etiological agent of this disease is a virus belonging to the
Orthomyxoviridae
family, named infectious salmon anemia virus (ISAV). Although it has been suggested that this virus can be vertically transmitted, even in freshwater, there is a lack of compelling experimental evidence to confirm this. Here we demonstrate significant putative viral loads in the ovarian fluid as well as in the eggs of two brood stock female adult specimens that harbored the virus systemically but without clinical signs. The target virus corresponded to a highly polymorphic region 3 (HPR-3) variant, which is known to be virulent in seawater and responsible for recent and past outbreaks of this disease in Chile. Additionally, the virus recovered from the fluid as well as from the interior of the eggs was fully infective to a susceptible fish cell line. To our knowledge, this is the first robust evidence demonstrating mother-to-offspring vertical transmission of the infective virus on the one hand and the asymptomatic transmission of a virulent form of the virus in freshwater fish on the other hand.

IMPORTANCE
The robustness of the data presented here will contribute to a better understanding of the biology of the virus but most importantly will constitute a key management tool in the control of an aggressive agent constantly threatening the sustainability of the global salmon industry.
Hepatitis C Virus NS5A Hijacks ARFGAP1 To Maintain a Phosphatidylinositol 4-Phosphate-Enriched Microenvironment
Authors: Li Hongyan , Yang Xiaojie , Yang Guangbo , Hong Zhi , Zhou Liya , Yin Peiqi , Xiao Yan , Chen Lingyi , Chung Raymond T. , Zhang Leiliang
Published: March 2014

Phosphatidylinositol 4-phosphate (PI4P) is well known to be upregulated during hepatitis C virus (HCV) replication. The role of PI4 kinases in HCV has been extensively investigated. Whether the PI4P phosphatase Sac1 is altered by HCV remains unclear. Here, we identified ARFGAP1 to be a novel host factor for HCV replication. We further show that Sac1 interacts with ARFGAP1 and inhibits HCV replication. The elevation of PI4P induced by HCV NS5A is abrogated when the coatomer protein I (COPI) pathway is inhibited. We also found an interaction between NS5A and ARFGAP1. Furthermore, we identified a conserved cluster of positively charged amino acids in NS5A critical for interaction between NS5A and ARFGAP1, induction of PI4P, and HCV replication. Our data demonstrate that ARFGAP1 is a host factor for HCV RNA replication. ARFGAP1 is hijacked by HCV NS5A to remove COPI cargo Sac1 from the site of HCV replication to maintain high levels of PI4P.
Our findings provide an additional mechanism by which HCV enhances formation of a PI4P-rich environment.

IMPORTANCE
PI4P is enriched in the replication area of HCV; however, whether PI4P phosphatase Sac1 is subverted by HCV is not established. The detailed mechanism of how COPI contributes to viral replication remains unknown, though COPI components were hijacked by HCV. We demonstrate that ARFGAP1 is hijacked by HCV NS5A to remove COPI cargo Sac1 from the HCV replication area to maintain high-level PI4P generated by NS5A. Furthermore, we identify a conserved cluster of positively charged amino acids in NS5A, which are critical for interaction between NS5A and ARFGAP1, induction of PI4P, and HCV replication. This study will shed mechanistic insight on how other RNA viruses hijack COPI and Sac1.
The efficacy of the Cook-Swartz implantable Doppler in the detection of free-flap compromise: a systematic review protocol
Authors: Agha Riaz A , Gundogan Buket , Fowler Alexander J , Bragg Thomas W H , Orgill Dennis P
Published: March 2014

Introduction

The Cook-Swartz implantable Doppler monitors venous or arterial blood flow from free flaps and can detect free-flap compromise. Previous studies have shown that the use of this Doppler can improve detection and salvage rates as it provides an earlier warning than the current method of clinical assessment. Such studies assert that the implantable Doppler is of great value in monitoring free flaps in current microsurgical units. This systematic review aims to compare the efficacy of the Cook-Swartz implantable Doppler in monitoring free-flap compromise against conventional clinical free-flap monitoring techniques.

Methods and analysis

Various electronic databases will be systematically searched for studies that compare the use of Cook-Swartz implantable Doppler with clinical assessment. The selected studies will then have their titles and abstracts screened by two authors. Articles selected after title and abstract screen will have full text downloaded and the complete article will be assessed for suitability. Once the articles have been selected for inclusion, data extraction will take place. For data analysis, the outcomes of the studies will be tabulated, with descriptive statistics performed as appropriate and the detection rate of the Doppler and clinical assessment will be compared and synthesised where possible.

Ethics and dissemination

The authors hope to disseminate the findings as widely as possible. This systematic review will be published in a peer-reviewed journal and include a number of recommendations as its conclusion based on the evidence contained within. Given the wide range of specialties now utilising flaps, it will be presented at a wide range of national and international conferences.

Protocol Registration in PROSPERO

CRD42013005818

The literature search and data extraction went on until 28 January 2014. These steps were revised in line with peer review comments.
Animal‐assisted interventions: making better use of the human‐animal bond
Authors: Mills Daniel , Hall Sophie
Published: March 2014

In the third of Veterinary Record 's series of articles promoting One Health, Daniel Mills and Sophie Hall discuss the therapeutic effects of companion animals, the influence of pets on childhood development and how researchers are elucidating the true value of animal companionship.
A review of developments in ballast water management
Authors: Balaji Rajoo , Yaakob Omar , Koh Kho King
Published: March 2014

Transportation and translocation of non-native species by ships through ballast water is one of the current issues the shipping industry is trying to address. The Ballast Water Convention is nearing full ratification after which treatment of ballast water will become mandatory for most of the trading merchant vessel categories. Ballast water management systems employing various technologies are commercially available but at high costs. Economics apart, the efficiency of these technologies and realistic ways to ensure compliance with stricter requirements of some Administrations are issues that need to be focussed upon. With the report of the Environmental Protection Agency as an assessment reference, this paper reviews the treatment technologies. Juxtaposing reports of Lloyd’s Register on the status, a concise overview of the technologies has been projected. A sustainable ballast water management based on data and assessments is proposed. The management must be extended to both shore and on-board platforms for practices, treatment, sampling, testing, and recycling. An exemplar system harvesting shipboard waste heat is projected as a route for thermal treatment in combination with technologies showing potential for optimized ballast water management.
Gauge invariant electromagnetic properties of fermions induced by CPT-violation in the Standard Model Extension
Authors: Moyotl A. , Novales-Sanchez H. , Toscano J. J. , Tututi E. S.
Published: March 2014

Low-energy Lorentz-invariant quantities could receive contributions from a fundamental theory producing small Lorentz-violating effects. Within the Lorentz-violating extension of quantum electrodynamics, we investigate, perturbatively, the contributions to the one-loop ffγ vertex from the CPT-violating axial coupling of a vector background field to fermions. We find that the resulting vertex function has a larger set of Lorentz structures than the one characterizing the usual, Lorentz-invariant, parametrization of the ffγ vertex. We prove gauge invariance of the resulting one-loop expression through a set of gauge invariant nonrenormalizable operators introducing new-physics effects at the first- and second-orders in Lorentz-violation, and which generate tree-level contributions to the ffγ vertex. Whereas loop contributions involving parameters that violate Lorentz-invariance at the first-order are CPT-odd, those arising at the second-order are CPT-even, so that contributions to low-energy physics are restricted to emerge for the first time at the second-order. In this context, we derive a contribution to anomalous magnetic moment (AMM) of fermions, which we use to set a bound on Lorentz-violation.
Adinkras and SUSY holography: Some explicit examples
Authors: Gates S. James , Hübsch T. , Stiffler Kory
Published: March 2014

We discuss the mechanism by which adinkras holographically store the required information for the Spin(1, 3) Clifford Algebra fiber bundle in the cases of three 4D, [Formula: see text] = 1 representations: the chiral, vector and tensor supermultiplets.
Systematic study of rapidity dispersion parameter in high energy nucleus–nucleus interactions
Authors: Bhattacharyya Swarnapratim , Haiduc Maria , Neagu Alina Tania , Firu Elena
Published: March 2014

A systematic study of rapidity dispersion parameter as a quantitative measure of clustering of particles has been carried out in the interactions of 16 O , 28 Si and 32 S projectiles at 4.5 A GeV/c with heavy ( AgBr ) and light (CNO) groups of targets present in the nuclear emulsion. For all the interactions, the total ensemble of events has been divided into four overlapping multiplicity classes depending on the number of shower particles. For all the interactions and for each multiplicity class, the rapidity dispersion parameter values indicate the occurrence of clusterization during the multiparticle production at Dubna energy. The measured rapidity dispersion parameter values are found to decrease with the increase of average multiplicity for all the interactions. The dependence of rapidity dispersion parameter on the average multiplicity can be successfully described by a relation D(η) = a + b〈ns〉 + c〈ns〉2. The experimental results have been compared with the results obtained from the analysis of Monte Carlo simulated (MC-RAND) events. MC-RAND events show weaker clusterization among the pions in comparison to the experimental data.
SIGNIFICANCE OF THE ELECTROMYOGRAPHIC ANALYSIS OF THE UPPER LIMB MUSCLES OF CRICKET BOWLERS: RECOMMENDATIONS FROM STUDIES OF OVERHEAD-THROWING ATHLETES
Authors: AHAMED NIZAM UDDIN , SUNDARAJ KENNETH , AHMAD BADLISHAH , RAHMAN MATIUR , ALI MD. ASRAF , ISLAM MD. ANAMUL
Published: March 2014

The purpose of this study was twofold: (i) to review the existing literature on electromyographic (EMG) analysis of the upper limb muscles of present overhead-throwing (OT) athletes during throwing and of cricket bowlers (CBs) during cricket bowling (CB) and, (ii) to discuss the importance of and generate recommendations for the EMG assessment of the muscle activity of CBs with respect to previous studies of OT athletes. A literature search of the PubMed, Scopus and Google Scholar electronic databases was performed to identify relevant articles published up to December 2012. This search was performed to evaluate the following areas, (i) what are the upper limb muscles that should be evaluated during OT sports and cricket bowling? (ii) what types of EMG methodologies have been used? (iii) what are the anthropometric, performance and physical functional variables that are usually selected? and (iv) what recommendations can be made for the assessment of the muscle activity of CBs? The search identifies 32 publications on OT athletes and 4 on CBs. The results note the following conclusions: (i) there are relatively few CB-related papers that utilize EMG, particularly for the assessment of muscle activity and coordination, (ii) a total of 22 upper limb muscles were investigated using EMG (from both criteria), (iii) surface electrodes are used more frequently than needle electrodes, (iv) most of the article normalized and analyzed the EMG amplitudes than the frequency, and the data was more often analyzed through a descriptive statistical analysis and (v) the majority of the studies analyzed the right limb of physically normal (uninjured) male's both the amateur and professional athletes that were 20 to 29 years of age. Finally, the published evidence on CBs is inadequate to validate a sound recommendation for the assessment of the muscles of CBs using EMG. However, the studies on OT athletes do provide guidelines that can be used to analyze CBs. The overall conclusion of this review show that, further studies are needed to evaluate the efficacy of EMG for the assessment of the upper limb muscle of CBs to ultimately identify and prevent injury which is still a matter of discussion in the sports medicine community.
Al Khlata glacial deposits in the Oman Mountains and their implications
Authors: Heward A. P. , Penney R. A.
Published: March 2014

A thick succession of Al Khlata glacio-lacustrine deposits, including diamictites, crops out in the Wadi Daiqa inlier and there are other possible Al Khlata outcrops in Wadi Amdeh and Wadi al Arabiyin. These outcrops in the Oman Mountains are 100 km north of where the Al Khlata had been thought to pinch out by non-deposition or erosion. Fossil spores and pollen from Wadi Daiqa are highly carbonized having been subject to greenschist facies metamorphism, but are still clearly identifiable as taxa from the Late Carboniferous 2159A zone of the oil-producing areas of interior Oman. This northernmost Al Khlata is sand rich and interpreted to be glacio-lacustrine. Previously the sand-dominated Al Khlata successions north of the Central Oman High have been considered to be glacio-fluvial outwash largely based on their context. The Al Khlata deposits in Wadi Daiqa and the underlying several-kilometre-thick Amdeh succession are preserved in Saih Hatat, probably in a continuation of the Ghaba Salt Basin that itself overlies an accreted terrane from the Pan African orogeny.
Near-surface diagenesis of ophiolite-derived conglomerates of the Barzaman Formation, United Arab Emirates: a natural analogue for permanent CO
2
sequestration via mineral carbonation of ultramafic rocks
Authors: Lacinska Alicja Magdalena , Styles Michael Thomas , Farrant Andrew Roger
Published: March 2014

Carbon capture and storage by mineralization is a potential method for storing anthropogenic CO
2
emissions, and is based on the reaction between Mg silicate and CO
2
to form Mg carbonate. The conglomerates of the Barzaman Formation exposed in the eastern United Arab Emirates represent an excellent natural analogue of this process. These conglomerates were deposited as a series of alluvial fans along the western margin of the Hajar Mountains, part of the Oman-UAE Ophiolite, and are composed largely of ultramafic and lesser-mafic clasts. The clasts and matrix have been extensively altered to dolomite during diagenetic processes. Analysis and interpretation of rock textures provide evidence for the various factors that influenced the diagenetic processes and shed light on the silicate–carbonate transformation process. All the reactions have taken place in the near-surface environment; the silicate–carbonate conversion reaction is exothermic and occurs spontaneously at near-ambient pressure and temperature, probably no greater than 50 °C. Estimates of the amount of CO
2
stored in this way can be obtained from considerations of outcrop area, formation thickness and percentage of dolomite replacement, and show that
c.
150 billion tonnes (equivalent to about 4 years of worldwide CO
2
emissions at current rates) are stored.
Magma genesis controlled by tectonic styles in the northern part of the Arabia plate during Cenozoic time
Authors: Al-Kwatli Mohamad Amer , Gillot Pierre Yves , Lefèvre Jean Claude , Hildenbrand Anthony , Kluska Jean-Michel
Published: March 2014

Widespread lava fields in the northern part of the Arabian platform are the subject of an open geodynamic debate on the origin of the intraplate volcanism. We present new K–Ar ages and whole-rock geochemical data for lava flows from Syria, which allow us to propose a new model of volcano-tectonic evolution highlighting how tectonics have controlled magma genesis in the region during the last 18 Ma. The Cenozoic Syrian lavas are alkaline and subalkaline rocks, typical of magma erupted in such a continental intraplate context. Basaltic samples from different Syrian volcanic provinces show significant variations in terms of incompatible trace element signatures. Crustal contamination plays a negligible role during magma migration and differentiation, and crystal fractionation is essentially restricted to olivine and clinopyroxene. Our results suggest that the Syrian lavas have been generated by variable degrees of partial melting (
c.
1–10%) from different levels of a locally heterogeneous lithospheric mantle. The light/medium rare Earth element (LREE/MREE) ratios not only illustrate how the degree of partial melting has changed spatially and temporally during the last
c.
18 Ma, but also indicate that the degree and the style of extensional tectonics has changed through time. We conclude that the Cenozoic Syrian volcanism is a consequence of extensional tectonics, under periodical influence of the north- and eastwards convergence at the Arabia–Eurasia margin, which induces rotational tectonic styles. This controls the partial melting at various depths in the mantle. The volcanism of northern Arabia developed in the framework of the Red Sea rifting and initiated at the same time as the southern Red Sea volcanism. It extends up to historical time, progressively smoothed to the north in a contradictory relation with the compressional/extensional setting of the Arabia–Eurasia margin.

Supplementary material:

Further information on the analytical results is available at
http://www.geolsoc.org.uk/SUP18681
.
Neoproterozoic evolution of the eastern Arabian basement based on a refined geochronology of the Marbat region, Sultanate of Oman
Authors: Rantakokko Nina E. , Whitehouse Martin J. , Pease Victoria , Windley Brian F.
Published: March 2014

New high spatial resolution secondary ion mass spectrometry (SIMS) U–Pb zircon data from the Sadh gneiss complex and the intruding Marbat granodiorite of the Marbat region, southern Sultanate of Oman, yield Cryogenian magmatic protolith ages for gneisses ranging from
c.
850 to 830 Ma. Zircon ages record a
c.
815–820 Ma period of deformation and migmatization, followed by intrusion of a hornblende gabbro/diorite and the undeformed Marbat granodiorite at
c.
795 Ma. Following break-up and rifting of Rodinia at
c.
870 Ma, crustal growth in the Marbat region occurred via arc accretion at
c.
850–790 Ma, possibly in the easternmost part of the Mozambique Ocean based on earlier cessation of accretion here compared to the Arabian–Nubian Shield. Similarity of the new zircon geochronology to peaks of detrital zircon ages in the unconformably overlying Ediacaran Marbat sandstone suggests relatively local derivation from uplifted basement for the latter.

Supplementary material:

Detailed petrographic descriptions and photographs of hand specimens and thin-sections are available at
http://www.geolsoc.org.uk/SUP18685
.
Structure of the metamorphic sole to the Oman Ophiolite, Sumeini Window and Wadi Tayyin: implications for ophiolite obduction processes
Authors: Cowan R. J. , Searle M. P. , Waters D. J.
Published: March 2014

Two localities where the inverted metamorphic sole of the Oman Ophiolite are best exposed, Sumeini Window and Wadi Tayyin, have been mapped and sampled in greater detail. In both areas an inverted pressure and temperature profile is exposed beneath the Semail Thrust, the base of the ophiolite, from garnet+clinopyroxene-bearing granulite to hornblende+plagioclase amphibolite down through epidote amphibolite and a variety of greenschist facies metasediments, dominantly cherts, marbles and quartzites. Thermobarometry on garnet- and clinopyroxene-bearing amphibolites immediately beneath the contact with mantle sequence harzburgites shows that the upper sole rocks formed at pressure–temperature (
P–T
) conditions of 770–900 °C and 11–13 kbar, equivalent to depths of 30–40 km in oceanic lithosphere. Heat for metamorphism can only have been derived from the overlying mantle sequence peridotites. Pressures are higher than can be accounted for by the thickness of the ophiolite (15–20 km). Timing of peak metamorphism was synchronous with the formation of the ophiolite gabbroic–trondhjemite crustal sequence and eruption of the pillow lavas (Cenomanian; 96–95 Ma). Metamorphic sole rocks have been structurally repeated by imbricate thrusting, casting doubt on previous estimates of thermal gradients. All the data support a subduction zone setting for metamorphism and a supra-subduction zone environment for ophiolite formation during the Cenomanian.
Methodological differences account for inconsistencies in reported free VEGF concentrations in pregnant rats
Authors: Weissgerber Tracey L. , McConico Andrea , Knudsen Bruce E. , Butters Kim A. , Hayman Suzanne R. , White Wendy M. , Milic Natasa , Miller Virginia M. , Garovic Vesna D.
Published: March 2014

Free vascular endothelial growth factor (VEGF) is undetectable in plasma during human pregnancy. However, studies examining pregnant rats have reported both low (8–29 pg/ml) and high (527–1,030 pg/ml) free VEGF. These discrepancies cast uncertainty over the use of rat models to study angiogenic factors in pregnancy and preeclampsia. This study investigates methodological factors that may explain these discrepancies. Plasma VEGF in nonpregnant, day 7 pregnant, and day 19 pregnant rats was measured using rat and mouse ELISAs (R&D Systems). The rat ELISA detected VEGF in plasma from nonpregnant rats but not in plasma from day 19 pregnant rats. The mouse ELISA detected higher VEGF concentrations than the rat ELISA in every sample tested. This discrepancy was greater in day 19 pregnant rats (median: 2,273 vs. 0 pg/ml) than in nonpregnant (97 vs. 20 pg/ml) and day 7 pregnant (66 vs. 2 pg/ml) rats. Recovery of recombinant rat VEGF (rrVEGF) spiked into plasma from nonpregnant and day 7 pregnant rats was high for the rat ELISA (82–105%) but low for the mouse ELISA (17–22%). The rat ELISA did not recover rrVEGF in plasma from day 19 pregnant rats, suggesting that this ELISA measures free VEGF. The use of the rat versus mouse ELISA likely explains the differences in reported VEGF concentrations in pregnant rats. While the rat ELISA appears to measure free VEGF, plasma concentrations in nonpregnant and pregnant rats are below the assay sensitivity limit. As most previous studies of pregnant rats used the mouse VEGF ELISA, these data should be interpreted cautiously.
Endogenous Tim-1 promotes severe systemic autoimmunity and renal disease MRL-Faslprmice
Authors: Nozaki Yuji , Kitching A. Richard , Akiba Hisaya , Yagita Hideo , Kinoshita Koji , Funauchi Masanori , Matsumura Itaru
Published: March 2014

The T-cell immunoglobulin mucin 1, also known as kidney injury molecule-1, modulates CD4+ T-cell responses and is also expressed by damaged proximal tubules within the kidney. Both Th subset imbalance (Th1/Th2/Th17) and regulatory T-cell and B-cell alterations contribute to the pathogenesis of autoimmune disease. This study investigated the effects of an inhibitory anti-T-cell immunoglobulin mucin 1 antibody (RMT1–10) in lupus-prone MRL- Faslprmice. MRL- Faslprmice were treated with RMT1–10 or a control antibody intraperitoneally twice weekly from 3 mo of age for 16 wk. RMT1–10 treatment significantly improved survival, limited the development of lymphadenopathy and skin lesions, preserved renal function and decreased proteinuria, reduced serum anti-DNA antibody levels, and attenuated renal leukocyte accumulation. Th1 and Th17 cellular responses systemically and intrarenally were reduced, but regulatory T and B cells were increased. RMT1–10 treatment also reduced glomerular immunoglobulin and C3 deposition and suppressed cellular proliferation and apoptosis. Urinary excretion and renal expression of kidney injury molecule-1 was reduced, reflecting diminished interstitial injury. As RMT1–10 attenuated established lupus nephritis, manipulating immune system T-cell immunoglobulin mucin 1 may represent a therapeutic strategy in autoimmune diseases affecting the kidney.
Differences in susceptibility to develop parameters of diabetic nephropathy in four mouse strains with type 1 diabetes
Authors: Franzén Stephanie , Friederich-Persson Malou , Fasching Angelica , Hansell Peter , Nangaku Masaomi , Palm Fredrik
Published: March 2014

One-third of diabetes mellitus patients develop diabetic nephropathy, and with underlying mechanisms unknown it is imperative that diabetic animal models resemble human disease. The present study investigated the susceptibility to develop diabetic nephropathy in four commonly used and commercially available mouse strains with type 1 diabetes to determine the suitability of each strain. Type 1 diabetes was induced in C57Bl/6, NMRI, BALB/c, and 129Sv mice by alloxan, and conscious glomerular filtration rate, proteinuria, and oxidative stress levels were measured in control and diabetic animals at baseline and after 5 and 10 wk. Histological alterations were analyzed using periodic acid-Schiff staining. Diabetic C57Bl/6 displayed increased glomerular filtration rate, i.e., hyperfiltration, whereas all other parameters remained unchanged. Diabetic NMRI developed the most pronounced hyperfiltration as well as increased oxidative stress and proteinuria but without glomerular damage. Diabetic BALB/c did not develop hyperfiltration but presented with pronounced proteinuria, increased oxidative stress, and glomerular damage. Diabetic 129Sv displayed proteinuria and increased oxidative stress without glomerular hyperfiltration or damage. However, all strains displayed intrastrain correlation between oxidative stress and proteinuria. In conclusion, diabetic C57Bl/6 and NMRI both developed glomerular hyperfiltration but neither presented with histological damage, although NMRI developed low-degree proteinuria. Thus these strains may be suitable when investigating the mechanism causing hyperfiltration. Neither BALB/c nor 129Sv developed hyperfiltration although both developed pronounced proteinuria. However, only BALB/c developed detectable histological damage. Thus BALB/c may be suitable when studying the roles of proteinuria and histological alterations for the progression of diabetic nephropathy.
Theoretical assessment of renal autoregulatory mechanisms
Authors: Sgouralis Ioannis , Layton Anita T.
Published: March 2014

A mathematical model of renal hemodynamics was used to assess the individual contributions of the tubuloglomerular feedback (TGF) mechanism and the myogenic response to glomerular filtration rate regulation in the rat kidney. The model represents an afferent arteriole segment, glomerular filtration, and a short loop of Henle. The afferent arteriole model exhibits myogenic response, which is activated by hydrostatic pressure variations to induce changes in membrane potential and vascular muscle tone. The tubule model predicts tubular fluid and Cl−transport. Macula densa Cl−concentration is sensed as the signal for TGF, which acts to constrict or dilate the afferent arteriole. With this configuration, the model afferent arteriole maintains stable glomerular filtration rate within a physiologic range of perfusion pressure (80–180 mmHg). The contribution of TGF to overall autoregulation is significant only within a narrow band of perfusion pressure values (80–110 mmHg). Model simulations of ramp-like perfusion pressure perturbations agree well with findings by Flemming et al. (Flemming B, Arenz N, Seeliger E, Wronski T, Steer K, Persson PB. J Am Soc Nephrol 12: 2253–2262, 2001), which indicate that changes in vascular conductance are markedly sensitive to pressure velocity. That asymmetric response is attributed to the rate-dependent kinetics of the myogenic mechanism. Moreover, simulations of renal autoregulation in diabetes mellitus predict that, due to the impairment of the voltage-gated Ca2+channels of the afferent arteriole smooth muscle cells, the perfusion pressure range in which single-nephron glomerular filtration rate remains stable is reduced by ∼70% and that TGF gain is reduced by nearly 40%, consistent with experimental findings.
Human mesenchymal stem cells alter macrophage phenotype and promote regeneration via homing to the kidney following ischemia-reperfusion injury
Authors: Wise Andrea F. , Williams Timothy M. , Kiewiet Mensiena B. G. , Payne Natalie L. , Siatskas Christopher , Samuel Chrishan S. , Ricardo Sharon D.
Published: March 2014

Mesenchymal stem cells (MSCs) ameliorate injury and accelerate repair in many organs, including the kidney, although the reparative mechanisms and interaction with macrophages have not been elucidated. This study investigated the reparative potential of human bone marrow-derived MSCs and traced their homing patterns following administration to mice with ischemia-reperfusion (IR) injury using whole body bioluminescence imaging. The effect of MSCs on macrophage phenotype following direct and indirect coculture was assessed using qPCR. Human cytokine production was measured using multiplex arrays. After IR, MSCs homed to injured kidneys where they afforded protection indicated by decreased proximal tubule kidney injury molecule-1 expression, blood urea nitrogen, and serum creatinine levels. SDS-PAGE and immunofluorescence labeling revealed MSCs reduced collagen α1(I) and IV by day 7 post-IR. Gelatin zymography confirmed that MSC treatment significantly increased matrix metalloproteinase-9 activity in IR kidneys, which contributed to a reduction in total collagen. Following direct and indirect coculture, macrophages expressed genes indicative of an anti-inflammatory “M2” phenotype. MSC-derived human GM-CSF, EGF, CXCL1, IL-6, IL-8, MCP-1, PDGF-AA, and CCL5 were identified in culture supernatants. In conclusion, MSCs home to injured kidneys and promote repair, which may be mediated by their ability to promote M2 macrophage polarization.
Na+-K+-2Cl−cotransporter-mediated fluid secretion increases under hypotonic osmolarity in the mouse submandibular salivary gland
Authors: Kidokoro Manami , Nakamoto Tetsuji , Mukaibo Taro , Kondo Yusuke , Munemasa Takashi , Imamura Atsushi , Masaki Chihiro , Hosokawa Ryuji
Published: March 2014

Water-handling epithelia are sensitive to the osmotic environment. In this study, the effects of a hypo-osmotic challenge on carbachol (CCh)-induced fluid secretion was investigated using an ex vivo submandibular gland perfusion technique and intracellular pH and Ca2+measurements. The osmolality of the perfusion solution was altered to examine the response of the gland to a hypotonic challenge. The flow rate was increased by 34% with a 30% hypotonic solution (225 mosmol/kgH2O), although the Ca2+response was unchanged. The lowering of the external Cl−by 50% abolished this increase in the 30% hypotonic solution. Furthermore, bumetanide, an inhibitor of the Na+-K+-2Cl−cotransporter (NKCC1), completely inhibited the fluid secretion increase caused by the 30% hypotonic solution, and both the total amount of fluid and the flow rate were identical to those of the isotonic solution. This finding was confirmed by measuring the NKCC1 bumetanide-dependent NH4+transport; Na+-K+-2Cl−transport was upregulated >40% by a 30% hypotonic challenge. Therefore, the increase in CCh-induced fluid secretion in response to hypotonic conditions can be attributed, to a large extent, to the specific activation of the NKCC1.
Voluntary and involuntary running in the rat show different patterns of theta rhythm, physical activity, and heart rate
Authors: Li Jia-Yi , Kuo Terry B. J. , Yen Jiin-Cherng , Tsai Shih-Chih , Yang Cheryl C. H.
Published: March 2014

Involuntarily exercising rats undergo more physical and mental stress than voluntarily exercising rats; however, these findings still lack electrophysiological evidence. Many studies have reported that theta rhythm appears when there is mental stress and that it is affected by emotional status. Thus we hypothesized that the differences between voluntary and involuntary movement should also exist in the hippocampal theta rhythm. Using the wheel and treadmill exercise models as voluntary and involuntary exercise models, respectively, this study wirelessly recorded the hippocampal electroencephalogram, electrocardiogram, and three-dimensional accelerations of young male rats. Treadmill and wheel exercise produced different theta patterns in the rats before and during running. Even though the waking baselines for the two exercise types were recorded in different environments, there did not exist any significant difference after distinguishing the rats' sleep/wake status. When the same movement-related parameters are considered, the treadmill running group showed more changes in their theta frequency (4–12 Hz), in their theta power between 9.5–12 Hz, and in their heart rate than the wheel running group. A positive correlation between the changes in high-frequency (9.5–12 Hz) theta power and heart rate was identified. Our results reveal various voluntary and involuntary changes in hippocampal theta rhythm as well as divergences in heart rate and high-frequency theta activity that may represent the effects of an additional emotional state or the sensory interaction during involuntary running by rats.
Integral Majorization Theorem for Invex Functions
Authors: Adil Khan M. , Kılıçman Adem , Rehman N.
Published: March 2014

We obtain some general inequalities and establish integral inequalities of the majorization type for invex functions. We give applications to relative invex functions.
A Study on Compressive Anisotropy and Nonassociated Flow Plasticity of the AZ31 Magnesium Alloy in Hot Rolling
Authors: Wang Guoqiang , Qian Xiaolei , Li Xuefei , Hou Haijing , Liu Yi , Lou Yanshan
Published: March 2014

Effect of anisotropy in compression is studied on hot rolling of AZ31 magnesium alloy with a three‐dimensional constitutive model based on the quadratic Hill48 yield criterion and nonassociated flow rule (non‐AFR). The constitutive model is characterized by compressive tests of AZ31 billets since plastic deformations of materials are mostly caused by compression during rolling processes. The characterized plasticity model is implemented into ABAQUS/Explicit as a user‐defined material subroutine (VUMAT) based on semi‐implicit backward Euler′s method. The subroutine is employed to simulate square‐bar rolling processes. The simulation results are compared with rolled specimens and those predicted by the von Mises and the Hill48 yield function under AFR. Moreover, strip rolling is also simulated for AZ31 with the Hill48 yield function under non‐AFR. The strip rolling simulation demonstrates that the lateral spread generated by the non‐AFR model is in good agreement with experimental data. These comparisons between simulation and experiments validate that the proposed Hill48 yield function under non‐AFR provides satisfactory description of plastic deformation behavior in hot rolling for AZ31 alloys in case that the anisotropic parameters in the Hill48 yield function and the non‐associated flow rule are calibrated by the compressive experimental results.
Remanufacturing the Pinion: An Application of a New Design Method for Spiral Bevel Gears
Authors: Lei Baozhen , Cheng Guang , Löwe Harald , Wang Xunwei
Published: March 2014

Damages of a large spiral bevel gear drive as used in heavy industry typically affect the pinion. Even if the gear still could be used, the complete pair has to be changed. This leads to long off times, high costs, and unnecessary waste. This paper applies a recent design technology for spiral bevel gears to the production of a replacement pinion for the sake of energy saving, reduction of costs and off times, and for the realization of green engineering. The process involves the following steps. First, the real tool surface of the gear is measured by a CMM. Based on the new design method, the tooth surface of the mating pinion is derived from this discrete point cloud. In order to improve the meshing performance, the resulting surface of the pinion is modified in the third step. Finally, the pinion is produced on a CNC machining center. In contrast to other approaches, none of these steps needs the parameters of the special machine tool defining the original gear pair. It is worth noting that our technology can also be profitable to gain more freedom in the design of new gear pairs.
A New Feigenbaum-Like Chaotic 3D System
Authors: Zhao Huitao , Lin Yiping , Dai Yunxian
Published: March 2014

Based on Sprott N system, a new three-dimensional autonomous system is reported. It is demonstrated to be chaotic in the sense of having positive largest Lyapunov exponent and fractional dimension. To further understand the complex dynamics of the system, some basic properties such as Lyapunov exponents, bifurcation diagram, Poincaré mapping, and period-doubling route to chaos are analyzed with careful numerical simulations. The obtained results also show that the period-doubling sequence of bifurcations leads to a Feigenbaum-like strange attractor.
Reattack of a Certificateless Aggregate Signature Scheme with Constant Pairing Computations
Authors: Tu Hang , He Debiao , Huang Baojun
Published: March 2014

A new attack against a novel certificateless aggregate signature scheme with constant pairing computations is presented. To enhance security, a new certificateless signature scheme is proposed first. Then a new certificateless aggregate signature scheme with constant pairing computations based on the new certificateless signature scheme is presented. Security analysis shows that the proposed certificateless aggregate signature scheme is provably secured in the random oracle.
Optimal Finite Cancer Treatment Duration by Using Mixed Vaccine Therapy and Chemotherapy: State Dependent Riccati Equation Control
Authors: Ghaffari Ali , Nazari Mostafa , Arab Farhad
Published: March 2014

The main objective of this paper is to propose an optimal finite duration treatment method for cancer. A mathematical model is proposed to show the interactions between healthy and cancerous cells in the human body. To extend the existing models, the effect of vaccine therapy and chemotherapy are also added to the model. The equilibrium points and the related local stability are derived and discussed. It is shown that the dynamics of the cancer model must be changed and modified for finite treatment duration. Therefore, the vaccine therapy is used to change the parameters of the system and the chemotherapy is applied for pushing the system to the domain of attraction of the healthy state. For optimal chemotherapy, an optimal control is used based on state dependent Riccati equation (SDRE). It is shown that, in spite of eliminating the treatment, the system approaches the healthy state conditions. The results show that the development of optimal vaccine-chemotherapy protocols for removing tumor cells would be an appropriate strategy in cancer treatment. Also, the present study states that a proper treatment method not only reduces the population of the cancer cells but also changes the dynamics of the cancer.