bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and DNA‐binding study of imidazole linked thiazolidinone derivatives
Authors: War Javeed Ahmad , Srivastava Santosh Kumar , Srivastava Savitri Devi
Published: May 2016

A novel series of imidazole‐linked thiazolidinone hybrid molecules were designed and synthesized through a feasible synthetic protocol. The molecules were characterized with Fourier transform infrared (FT‐IR), 1H nuclear magnetic resonance (NMR), 13C NMR and high‐resolution mass spectrometry (HRMS) techniques. In vitro susceptibility tests against Gram‐positive (S. aureus and B. subtilis) and Gram‐negative bacteria (E. coli and P. aeruginosa) gave highly promising results. The most active molecule (3e) gave a minimal inhibitory concentration (MIC) value of 3.125 μg/mL which is on par with the reference drug streptomycin. Structure–activity relationships revealed activity enhancement by nitro and chloro groups when they occupied meta position of the arylidene ring in 2‐((3‐(imidazol‐1‐yl)propyl)amino)‐5‐benzylidenethiazolidin‐4‐ones. DNA‐binding study of the most potent molecule 3e with salmon milt DNA (sm‐DNA) under simulated physiological pH was probed with UV–visible absorption, fluorescence quenching, gel electrophoresis and molecular docking techniques. These studies established that compound 3e has a strong affinity towards DNA and binds at DNA minor groove with a binding constant (Kb) 0.18 × 102 L mol−1. Molecular docking simulations predicted strong affinity of 3e towards DNA with a binding affinity (ΔG) ‐8.5 kcal/mol. Van der Waals forces, hydrogen bonding and hydrophobic interactions were predicted as the main forces of interaction. The molecule 3e exhibited specific affinity towards adenine–thiamine base pairs. Copyright © 2016 John Wiley & Sons, Ltd.
Ethylenedisalicylic Acid Derivatives as Dual Inhibitors of PTP1B and IKKβ and their Antiobesity and Antidiabetic Effects in Mice
Authors: Aher Nilkanth G. , Park Ji‐Won , Park Byung Ho , Kim Chan Kyung , Han Inn‐Oc , Cho Hyeongjin
Published: May 2016

Ethylenedisalicylic acid (EDSA) was developed as a novel scaffold for dual inhibitors of protein tyrosine phosphatase (PTP) 1B and IkB kinase β (IKKβ). EDSA is a modified version of methylenedisalicylic acid (MDSA) and contains two salicylate moieties connected by an ethylene moiety. In this study, derivatives of EDSA were synthesized and their inhibitory potencies against PTP1B and IKKβ were investigated. Many of these derivatives exhibited half‐maximal inhibitory concentrations (IC50s) in the low micromolar range. The metabolic effects of
ESA4
, 7, and 8 were further examined in a mouse model system.
ESA4
and
ESA8
significantly suppressed diet‐induced weight gain, whereas
ESA7
had a marginal effect.
ESA4
, 7, and 8 also lowered fasting glucose levels and accelerated glucose clearance rates after glucose injection. These observations indicate that EDSA scaffold‐based compounds are promising candidates for the treatment of obesity and diabetes.
An inter‐laboratory cross‐validation study for the determination of perampanel in human plasma by liquid chromatography assays
Authors: Mano Yuji
Published: May 2016

For sample assay to support global clinical studies of perampanel, a novel AMPA receptor antagonist, six chromatographic assay methods in human plasma were developed and fully validated at each laboratory using liquid chromatography with tandem mass spectrometry (LC‐MS/MS) or LC with fluorescence detection (LC‐FL). In this study, samples fortified with known perampanel concentrations were assayed at six laboratories to find whether assay data are comparable. Perampanel was extracted by protein precipitation or liquid–liquid extraction, chromatographed on a reverse‐phase column then detected by MS/MS or FL to achieve the limit of quantification of 0.25 or 1 ng/mL. Cross‐validation samples at four concentrations prepared at a central laboratory were determined at six laboratories and the mean accuracy at each concentration was within ±15% except the low concentration at one laboratory (relative error −17.4%), suggesting that plasma concentrations of perampanel in clinical trials can be compared across laboratories.
Accuracy and procedural characteristics of standard needle compared with radiofrequency needle transseptal puncture for structural heart interventions
Authors: Sharma Gaurav , Singh Gagan D. , Smith Thomas W. , Fan Dali , Low Reginald I. , Rogers Jason H.
Published: May 2016

Objectives

Our objectives were to assess for differences between standard and radiofrequency (RF) needle in procedural times, success, and spatial accuracy.

Background

Targeted transseptal (TS) puncture is essential for structural heart interventions. Spatial accuracy of standard versus RF needle has not been reported.

Methods

Consecutive patients undergoing structural heart interventions requiring TS puncture were studied retrospectively. A standard needle was alternated with a RF needle. Procedural success and times were recorded. Measurements based on intraprocedural transesophageal echocardiograms of the intended versus final TS crossing site were obtained. Pre‐puncture and maximal tenting of the septum were also recorded.

Results

Twenty‐five patients underwent standard needle and 27 RF TS access. All RF needle attempts to cross were successful without an assistance wire. Three standard needle patients required assisted crossing. After failed TS access, two patients had successful RF TS access. TS procedural times significantly favored the RF needle for time from septum to puncture (P = 0.02). Both standard and RF access yielded accurate crossing with no significant differences between the intended and actual crossing site. Maximal tenting was significantly less with the RF needle (P = 0.004). There were no major complications.

Conclusions

In the hands of an experienced operator, there were no major clinically significant differences between the standard and RF needle approaches. However, procedural unassisted crossing success was higher with the RF needle approach as compared to standard needle. Procedural times and degree of septum tenting favored the RF over standard needle. Accuracy was similar with both approaches. RF was a successful strategy when standard needle failed. There were no major complications with either TS puncture strategy. © 2016 Wiley Periodicals, Inc.
ChemInform Abstract: Polarization Spectroscopy of SrI in a Heat Pipe: The B2ε+‐X2ε+(0,0) System.
Authors: SCHROEDER J. O. + , NITSCH C. , ERNST W. E.
Published: May 2016

Spectra of the B2ε+‐X2ε+(0,0) transition around 674 nm of SrI, produced from the reaction of Sr and NaI in a heat pipe oven, are recorded using Doppler‐free laser polarization spectroscopy.
ChemInform Abstract: Chemical Sources of Singlet Oxygen. Part 3. Peroxidation of Water‐Soluble Singlet Oxygen Carriers with the Hydrogen Peroxide‐Molybdate System.
Authors: AUBRY J. M. , CAZIN B. , DUPRAT F.
Published: May 2016

The β‐naphthalenepropionic acid (I) is oxidized under controlled conditions with singlet oxygen, generated from hydrogen peroxide and sodium molybdate in alkaline solution via a diperoxomolybdate, to form the endo‐peroxide (II).
Exome sequencing of extreme clopidogrel response phenotypes identifies B4GALT2 as a determinant of on‐treatment platelet reactivity
Authors: Scott SA , Collet J‐P , Baber U , Yang Y , Peter I , Linderman M , Sload J , Qiao W , Kini AS , Sharma SK , Desnick RJ , Fuster V , Hajjar RJ , Montalescot G , Hulot J‐S
Published: May 2016

Interindividual variability in platelet aggregation is common among patients treated with clopidogrel and both high on‐treatment platelet reactivity (HTPR) and low on‐treatment platelet reactivity (LTPR) increase risks for adverse clinical outcomes. CYP2C19 influences clopidogrel response but only accounts for ∼12% of the variability in platelet reactivity. To identify novel variants implicated in on‐treatment platelet reactivity, patients with coronary artery disease (CAD) with extreme pharmacodynamic responses to clopidogrel and wild‐type CYP2C19 were subjected to exome sequencing. Candidate variants that clustered in the LTPR subgroup subsequently were genotyped across the discovery cohort (n = 636). Importantly, carriers of B4GALT2 c.909C>T had lower on‐treatment P2Y12 reaction units (PRUs; P = 0.0077) and residual platelet aggregation (P = 0.0008) compared with noncarriers, which remained significant after adjusting for CYP2C19 and other clinical variables in both the discovery (P = 0.0298) and replication (n = 160; PRU: P = 0.0001) cohorts. B4GALT2 is a platelet‐expressed galactosyltransferase, indicating that B4GALT2 c.909C>T may influence clopidogrel sensitivity through atypical cell‐surface glycoprotein processing and platelet adhesion.
Tuning the Carbon Dioxide Absorption in Amino Acid Ionic Liquids
Authors: Firaha Dzmitry S. , Kirchner Barbara
Published: May 2016

One of the possible solutions to prevent global climate change is the reduction of CO2 emissions, which is highly desired for the sustainable development of our society. In this work, the chemical absorption of carbon dioxide in amino acid ionic liquids was studied through first‐principles methods. The use of readily accessible and biodegradable amino acids as building blocks for ionic liquids makes them highly promising replacements for the widely applied hazardous aqueous solutions of amines. A detailed insight into the reaction mechanism of the CO2 absorption was obtained through state‐of‐the‐art theoretical methods. This allowed us to determine the reason for the specific CO2 capacities found experimentally. Moreover, we have also conducted a theoretical design of ionic liquids to provide valuable insights into the precise tuning of the energetic and kinetic parameters of the CO2 absorption.
Free fatty acids sensitize dendritic cells to amplify TH1/TH17‐immune responses
Authors: Stelzner Kristin , Herbert Diana , Popkova Yulia , Lorz Axel , Schiller Jürgen , Gericke Martin , Klöting Nora , Blüher Matthias , Franz Sandra , Simon Jan C. , Saalbach Anja
Published: May 2016

Obesity is associated with body fat gain and impaired glucose metabolism. Here, we identified both body fat gain in obesity and impaired glucose metabolism as two independent risk factors for increased serum levels of free fatty acids (FFAs). Since obesity is associated with increased and/or delayed resolution of inflammation observed in various chronic inflammatory diseases such as psoriasis, we investigated the impact of FFAs on human monocyte‐derived and mouse bone marrow‐derived dendritic cell (DCs) functions relevant for the pathogenesis of chronic inflammation. FFAs such as palmitic acid (PA) and oleic acid (OA) did not affect the pro‐inflammatory immune response of DCs. In contrast, PA and OA sensitize DCs resulting in augmented secretion of TH1/TH17‐instructive cytokines upon pro‐inflammatory stimulation. Interestingly, obesity in mice worsened a TH1/TH17‐driven psoriasis‐like skin inflammation. Strong correlation of the amount of total FFA, PA, and OA in serum with the severity of skin inflammation points to a critical role of FFA in obesity‐mediated exacerbation of skin inflammation. Our data suggest that increased levels of FFAs might be a predisposing factor promoting a TH1/TH17‐mediated inflammation such as psoriasis in response to an inflammatory danger signal.
Natural Inhibitors of HMG‐CoA Reductase—An Insilico Approach Through Molecular Docking and Simulation Studies
Authors: Suganya Subramanian , Nandagopal Balaji , Anbarasu Anand
Published: May 2016

Plant products have always been considered for many important metabolic disorders due to its abundant medicinal properties. Alarming adverse effects of overuse of statins has been reported for patients with dyslipidemia. This study was aimed to identify compounds with potent anti‐dyslipidemic property from selected plants and analyze them for their efficiency in binding with HMG‐CoA reductase, a key enzyme in lipid metabolism. The docking studies indicate rutin as the best compound that can inhibit HMG‐CoA reductase as it had strong binding affinity to the enzyme. The molecular dynamics simulation studies confirmed the stability of the HMG‐CoA reductase–rutin complex. RMSD, RMSF, Rg, H‐bond results indicated that the HMG‐CoA reductase–rutin complex is highly stable. Presently, statins are not preferred for individuals with pre‐existing liver disease. Our study identified rutin as a promising lead compound which could be further developed into an anti‐dyslipidemic molecule. Our results will be a good starting point for future experimental and clinical studies and if the results from such studies match international standards plant derived rutin might emerge as a good alternative to statins. J. Cell. Biochem. 118: 52–57, 2017. © 2016 Wiley Periodicals, Inc.
High prevalence of diffuse large B‐cell lymphoma in occult hepatitis B virus‐infected patients in the Tohoku district in Eastern Japan
Authors: Tajima Katsushi , Takahashi Naoto , Ishizawa Kenichi , Murai Kazunori , Akagi Tomoaki , Noji Hideyoshi , Sasaki Osamu , Wano Masaharu , Itoh Jugoh , Kato Yuichi , Scichishima Tsutomu , Ishida Yoji , Harigae Hideo , Sawada Kenichi ,   for the Tohoku Hematology Forum
Published: May 2016

Occult hepatitis B virus (HBV) infection is a clinical challenge, but its relationship to clinicopathologic features and the risk of progression to malignant lymphoma (ML) are poorly defined. We estimated the prevalence of HBV infection of 1,358 patients with newly diagnosed ML. HBV infection was more prevalent in ML than in control patients. The occult HBV infection group had a higher median onset age, no liver or spleen involvement, and higher prevalence of diffuse large B‐cell lymphoma than the other groups, indicating that occult HBV infection is a distinct clinicopathologic entity. J. Med. Virol. 88:2206–2210, 2016. © 2016 Wiley Periodicals, Inc.
A pilot study on the incidence of severe photosensitivity reactions leading to hospitalization linked to topical ketoprofen and other medications in selected European regions
Authors: Cazzaniga Simone , Naldi Luigi , Lecchi Silvia , Kürzinger Marie‐Laure , Auclert Laurent , Gori Mario , Chosidow Olivier , Hercogova Jana
Published: May 2016

The aim of this study was to assess the prevalence of exposure to topical nonsteroidal anti‐inflammatory drugs (NSAIDs), particularly ketoprofen, in a convenience sample of the population, to obtain estimates of the incidence of severe photosensitivity leading to hospitalization, and to assess causative factors in three catchment areas: the Paris metropolitan area, the Lombardy region (Italy) and the Prague area. All cases of severe photosensitivity not explained by underlying conditions and admitted to hospitals in the selected areas were included in the study. Controls were patients consecutively admitted to hospitals, in the same areas, for an acute condition or for an elective procedure not suspected of being related to medication use. From October 2012 to September 2013, 920 controls were recruited (median age 44 years, 50.8% females); 8 severe photosensitivity cases were reported in the population aged 18–74 years of the 3 geographical areas during the 1‐year surveillance period, corresponding to an incidence rate of 4.81 cases per 10 million person‐years (95% confidence interval – CI, 2.07–9.48). Six controls reported 1‐month exposure to topical ketoprofen, with an estimated prevalence of 0.65% (95% CI, 0.24–1.42). The population attributable risk for severe photosensitivity reactions linked to ketoprofen was 11.92% (95% CI, −0.12–52.99). This study was conducted in selected European areas and showed that the incidence of severe photosensitivity reactions leading to hospitalization as well as the exposure rate to topical ketoprofen were low. Among topical NSAIDs, topical ketoprofen was the leading cause of photosensitivity reactions but accounted for a limited number of hospitalized cases. Probably most of the relevant reactions were managed in the outpatient setting and a community based case–control study is advisable.
International Climate Migration: Evidence for the Climate Inhibitor Mechanism and the Agricultural Pathway
Authors: Nawrotzki Raphael J. , Bakhtsiyarava Maryia
Published: May 2016

Research often assumes that, in rural areas of developing countries, adverse climatic conditions increase (climate driver mechanism) rather than reduce (climate inhibitor mechanism) migration, and that the impact of climate on migration is moderated by changes in agricultural productivity (agricultural pathway). Using representative census data in combination with high‐resolution climate data derived from the novel Terra Populus system, we explore the climate–migration relationship in rural Burkina Faso and Senegal. We construct four threshold‐based climate measures to investigate the effect of heatwaves, cold snaps, droughts, and excessive precipitation on the likelihood of household‐level international outmigration. Results from multilevel logit models show that excessive precipitation increases international migration from Senegal while heatwaves decrease international mobility in Burkina Faso, providing evidence for the climate inhibitor mechanism. Consistent with the agricultural pathway, interaction models and results from a geographically weighted regression reveal a conditional effect of droughts on international outmigration from Senegal, which becomes stronger in areas with high levels of groundnut production. Moreover, climate change effects show a clear seasonal pattern, with the strongest effects appearing when heatwaves overlap with the growing season and when excessive precipitation occurs prior to the growing season. Copyright © 2016 John Wiley & Sons, Ltd.
Al‐density variation as one driving force for void formation in PERC solar cells
Authors: Horbelt Renate , Ebert Stefanie , Ulbikaite Vaidvile , Hahn Giso , Job Reinhart , Terheiden Barbara
Published: May 2016

The reduction of void formation in local Al contact structures is of high interest in studies dealing with passivated emitter and rear contact (PERC) solar cells. So far, several processing parameters and their impact on local contact formation were investigated in detail. However, up to now density variation of Al in dependence on temperature and Si content in the melt were not taken into account as a principal reason for void formation. In this context the current assumption of a constant volume of the Al paste particles is discussed in more detail. Based on the results of energy dispersive X‐ray spectroscopy, void formation implies either an expansion of paste particles or their burst during contact formation.

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(© 2016 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)
‘Cry “HAVOC!” and Let Slip the Dogs of War’: Regulating Private Military and Security Companies
Authors: Van Oeveren Anna
Published: May 2016

The second biggest contingent in Iraq after US forces, contractors have become something of a staple in contemporary conflict resolution and peacekeeping operations. The rise of private security and military firms is not a recent phenomenon. It has been a given since the end of the Cold War, thanks to a particular momentum in the market for force. Traditional armed forces have had their budgets cut and have sometimes had to undergo drastic economic reforms. At the same time, the market for force has seen the arrival of huge numbers of highly qualified military personnel. These developments have been beneficial to the rise of private military and security companies. However, they have also exposed the weakness of international law and regulation (and EU regulation in particular) when it comes to dealing with these firms.
Bonfire red titles
Authors: Lingard Lorelei
Published: May 2016

None
Extreme run-up events on a vertical wall due to nonlinear evolution of incident wave groups
Authors: Akrish Gal , Rabinovitch Oded , Agnon Yehuda
Published: May 2016

Nonlinear evolution of long-crested wave groups can lead to extreme interactions with coastal and marine structures. In the present study the role of nonlinear evolution in the formation of extreme run-up events on a vertical wall is investigated. To this end, the fundamental problem of interaction between non-breaking water waves and a vertical wall over constant water depth is considered. In order to simulate nonlinear wave–wall interactions, the high-order spectral method is applied to a computational domain which aims to represent a two-dimensional wave flume. Wave generation is simulated at the flume entrance by means of the additional potential concept. Through this concept, the implementation of a numerical wavemaker is applicable. In addition to computational efficiency, the adopted numerical approach enables one to consider the evolution of nonlinear waves while preserving full dispersivity. Utilizing these properties, the influence of the nonlinear wave evolution on the wave run-up can be examined for a wide range of water depths. In shallow water, it is known that nonlinear evolution of incident waves may result in extreme run-up events due to the formation of an undular bore. The present study reveals the influence of the nonlinear evolution on the wave run-up in deep-water conditions. The results suggest that extreme run-up events in deep water may occur as a result of the disintegration of incident wave groups into envelope solitons.
A Closed-Form Dynamics of a Novel Fully Wrist Driven by Revolute Motors
Authors: Enferadi J. , Shahi A.
Published: May 2016

This paper proposes a systematic methodology to obtain a closed-form formulation for dynamics analysis of a novel spherical robot that is called a 3(RPSP)-S parallel manipulator. The proposed manipulator provides high rotational displacement of the moving platform for low angular displacement of the motors. The advised robot is suitable for repetitive oscillatory applications (for example, wrist and ankle rehabilitation and table of autopilot and gyroscope life test, etc.). First, we describe the structure of the proposed manipulator and solve the inverse kinematics problem of the manipulator. Next, based on the principle of virtual work, a methodology for deriving the dynamical equations of motion is developed. The elaborated approach shows that the inverse dynamics of the manipulator can be reduced to solving a system of three linear equations in three unknowns. Finally, a computational algorithm to solve the inverse dynamics of the manipulator is advised and several trajectories of the moving platform are simulated and verified by a special dynamics modeling commercial software (MSC ADAMS).
Whole-grain consumption and the risk of all-cause, CVD and cancer mortality: a meta-analysis of prospective cohort studies
Authors: Wei Honglei , Gao Zong , Liang Rui , Li Zengqiang , Hao Hong , Liu Xu
Published: May 2016

Results of the relationships between dietary whole-grain consumption and the risk of all-cause, CVD and cancer-specific mortality are mixed. We summarised the evidence based on a meta-analysis of prospective cohort studies. Pertinent studies were identified by searching articles in the MEDLINE and EMBASE databases up to 20 January 2016 and by reviewing the reference lists of the retrieved articles. Random-effects models were used to calculate summary relative risks (SRR) and 95 % CI. In all, eleven prospective studies (ten publications) were included in the meta-analysis. There were a total of 816 599 subjects and 89 251 cases of all-cause mortality. On the basis of the highest v. the lowest categories of intake, whole grains may be associated with a lower risk of mortality from all causes (SRR 0·87; 95 % CI 0·84, 0·90), CVD (SRR 0·81; 95 % CI 0·75, 0·89) and all cancers (SRR 0·89; 95 % CI 0·82, 0·96). For each 3 servings/d increase in whole-grain intake, there was a 19 % reduction in the risk of all-cause mortality (SRR 0·81; 95 % CI 0·76, 0·85), a 26 % reduction in CVD mortality (SRR 0·74; 95 % CI 0·66, 0·83) and a 9 % reduction in cancer mortality (SRR 0·91; 95 % CI 0·84, 0·98). The current meta-analysis provides some evidence that high intake of whole grains was inversely associated with the risk of all-cause, CVD and cancer-specific mortality. Further well-designed studies, including clinical trials and in different populations, are required to confirm our findings.
Molecular cloning and expression of the vitellogenin gene and its correlation with ovarian development in an invasive pest Octodonta nipae on two host plants
Authors: Li Jin-Lei , Tang Bao-Zhen , Hou You-Ming , Xie Yi-Xing
Published: May 2016

There is an ongoing relationship between host plants and herbivores. The nutrient substances and secondary compounds found in the host plant can not only impact the growth and development process of herbivores, but, more importantly, may also affect their survival and reproductive fitness. Vitellogenesis is the core process of reproductive regulation and is generally considered as a reliable indicator for evaluating the degree of ovarian development in females. Vitellogenin (Vg) plays a critical role in the synthesis and secretion of yolk protein. In this study, the full-length cDNA of the Vg gene in an alien invasive species, the nipa palm hispid beetle Octodonta nipae Maulik (Coleoptera: Chrysomelidae) (OnVg) was cloned and, the effect of host plant on the OnVg expression level and ovarian development was investigated. The results revealed that the OnVg was highly and exclusively expressed in adult females, but barely detectable in larvae, pupae and adult males. The relative expression level of OnVg and egg hatchability were much higher in females fed on Phoenix canariensis (their preferred host) than those fed on Phoenix roebelenii. A positive correlation relationship between OnVg expression and egg hatchability was also detected. Additionally, the anatomy of the female reproductive system showed that the ovaries of individuals fed on P. canariensis were considerably more developed than in females fed on P. roebelenii. The results may be applicable to many pest management situations through reproductive disturbance by alternating host plant species or varieties or by reproductive regulation through vitellogenesis mediated by specific endocrine hormones.
Effect of a multi-sided concave liner barrel design on thickness and roughness of teat-end hyperkeratosis
Authors: Haeussermann Angelika , Britten Justine , Britten Allan , Pahl Christian , Älveby Nils , Hartung Eberhard
Published: May 2016

In a round liner barrel, the force of the closing liner is transferred by the two opposite sides of the liner wall to the teat apex. Liners with a multi-sided barrel shape close at three or more planes and distribute their force to a larger area of the teat apex. The objective of the study was to investigate effects of a liner with a multi-sided concave barrel design on the degree of teat-end hyperkeratosis, thickness and roughness, and on the time delay until thickness or roughness of teat-end hyperkeratosis responded to the experimental liner. The investigations were done on two dairy farms, one in USA and one in Germany. A split-udder arrangement of liners was used, and control treatment was a liner with round barrel shape. The test period comprised 14 weeks in the first study and 16 weeks in the second study. Thickness of teat-end hyperkeratosis was influenced by farm and test week. Roughness was influenced by farm, test week and treatment. In the first study, the incidence of rough teat-end hyperkeratosis was about 28 and 42% lower in teats milked with the experimental liner than in teats milked with the control liner by test weeks 11 and 14, respectively. In the second study, incidence of rough teat-end hyperkeratosis was rare in general, and in addition hardly occurred in teats milked with the experimental liner. The results indicate that the barrel design of the experimental liner causes similar effects on different farms but magnitude of the effect depends on initial incidence of teat end hyperkeratosis in the herd.
Comparative morphology of the urohyal bone of fishes collected from the Persian Gulf and Oman Sea
Authors: Jawad Laith A. , Khahe Jahromi Fatima Laghai , Teimori Azad , Mehraban Hamidreza , Esmaeili Hamid R.
Published: May 2016

The urohyal is incorporated within the hyoid and branchial arches and performs a significant role in the mouth opening-closing mechanism of fishes, and is considered a synapomorphy of teleostean fishes. Morphological variation of the urohyal, in terms of size and shape parameters, can allow species identification. Morphology of the urohyal in 49 species belonging to 43 genera and 29 families from the Persian Gulf and from the Oman Sea were compared using size and shape measurements. The results examine the suitability of using the urohyal morphology in differentiating fish species from this region; highlighting the taxonomic value of the urohyal, which until now, had been studied little in terms of use as a diagnostic feature in the classification of teleosts.
Deformations of Fell bundles and twisted graph algebras
Authors: RAEBURN IAIN
Published: May 2016

We consider Fell bundles over discrete groups, and theC*-algebra which is universal for representations of the bundle. We define deformations of Fell bundles, which are new Fell bundles with the same underlying Banach bundle but with the multiplication deformed by a two-cocycle on the group. Every graph algebra can be viewed as theC*-algebra of a Fell bundle, and there are many cocycles of interest with which to deform them. We thus obtain many of the twisted graph algebras of Kumjian, Pask and Sims. We demonstate the utility of our approach to these twisted graph algebras by proving that the deformations associated to different cocycles can be assembled as the fibres of aC*-bundle.
Field Reports: Yes, They Will Add to the Prehospital and Disaster Knowledge Base
Authors: Fattah Sabina , Rehn Marius , Wisborg Torben
Published: May 2016

FattahS, RehnM, WisborgT. Field reports: yes, they will add to the prehospital and disaster knowledge base. Prehosp Disaster Med. 2016;31(4):461–461.
A genome-scale CRISPR-Cas9 screening method for protein stability reveals novel regulators of Cdc25A
Authors: Wu Yuanzhong , Zhou Liwen , Wang Xin , Lu Jinping , Zhang Ruhua , Liang Xiaoting , Wang Li , Deng Wuguo , Zeng Yi-Xin , Huang Haojie , Kang Tiebang
Published: May 2016

The regulation of stability is particularly crucial for unstable proteins in cells. However, a convenient and unbiased method of identifying regulators of protein stability remains to be developed. Recently, a genome-scale CRISPR-Cas9 library has been established as a genetic tool to mediate loss-of-function screening. Here, we developed a protein stability regulators screening assay (Pro-SRSA) by combining the whole-genome CRISPR-Cas9 library with a dual-fluorescence-based protein stability reporter and high-throughput sequencing to screen for regulators of protein stability. Using Cdc25A as an example, Cul4B-DDB1DCAF8 was identified as a new E3 ligase for Cdc25A. Moreover, the acetylation of Cdc25A at lysine 150, which was acetylated by p300/CBP and deacetylated by HDAC3, prevented the ubiquitin-mediated degradation of Cdc25A by the proteasome. This is the first study to report that acetylation, as a novel posttranslational modification, modulates Cdc25A stability, and we suggest that this unbiased CRISPR-Cas9 screening method at the genome scale may be widely used to globally identify regulators of protein stability.
Correction: Corrigendum: An integrative approach to investigate the respective roles of single-nucleotide variants and copy-number variants in Attention-Deficit/Hyperactivity Disorder
Authors: Lima Leandro de Araújo , Feio-dos-Santos Ana Cecília , Belangero Sintia Iole , Gadelha Ary , Bressan Rodrigo Affonseca , Salum Giovanni Abrahão , Pan Pedro Mario , Moriyama Tais Silveira , Graeff-Martins Ana Soledade , Tamanaha Ana Carina , Alvarenga Pedro , Krieger Fernanda Valle , Fleitlich-Bilyk Bacy , Jackowski Andrea Parolin , Brietzke Elisa , Sato João Ricardo , Polanczyk Guilherme Vanoni , Mari Jair de Jesus , Manfro Gisele Gus , do Rosário Maria Conceição , Miguel Eurípedes Constantino , Puga Renato David , Tahira Ana Carolina , Souza Viviane Neri , Chile Thais , Gouveia Gisele Rodrigues , Simões Sérgio Nery , Chang Xiao , Pellegrino Renata , Tian Lifeng , Glessner Joseph T. , Hashimoto Ronaldo Fumio , Rohde Luis Augusto , Sleiman Patrick M. A. , Hakonarson Hakon , Brentani Helena
Published: May 2016

Scientific Reports 6: Article number: 22851; published online: 07 March 2016; updated: 24 May 2016 The Acknowledgements section in this Article is incomplete. “This work was supported by the National Institute of Developmental Psychiatry for Children and Adolescents, a science and technology institute funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; National Council for Scientific and Technological Development; grant number 573974/2008-0) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; Research Support Foundation of the State of São Paulo; grant number 2008/57896-8).
Different prognostic value of circulating and disseminated tumor cells in primary breast cancer: Influence of bisphosphonate intake?
Authors: Kasimir-Bauer Sabine , Reiter Katharina , Aktas Bahriye , Bittner Ann-Kathrin , Weber Stephan , Keller Thomas , Kimmig Rainer , Hoffmann Oliver
Published: May 2016

Disseminated tumor cells (DTCs) in the bone marrow (BM) and circulating tumor cells (CTCs) in blood of breast cancer patients (pts) are known to correlate with worse outcome. Here we demonstrate a different prognostic value of DTCs and CTCs and explain these findings by early clodronate intake. CTCs (n = 376 pts) were determined using the AdnaTest BreastCancer (Qiagen Hannover GmbH, Germany) and DTCs (n = 525 pts) were analyzed by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Clodronate intake was recommended in case of DTC-positivity. CTCs were detected in 22% and DTCs in 40% of the pts, respectively. DTCs were significantly associated with nodal status (p = 0.03), grading (p = 0.01), lymphangiosis (p = 0.03), PR status (p = 0.02) and clodronate intake (p < 0.0001), no significant associations were demonstrated for CTCs. CTCs significantly correlated with reduced PFS (p = 0.0227) and negative prognostic relevance was predominantly related to G2 tumors (p = 0.044), the lobular (p = 0.024) and the triple-negative subtype (p = 0.005), HR-negative pts (p = 0.001), postmenopausal women (p = 0.013) and patients who had received radiation therapy (p = 0.018). No prognostic significance was found for DTCs. Therefore early clodronate intake can improve prognosis of breast cancer patients and CTCs might be a high risk indicator for the onset of metastasis not limited to bone metastasis.
Causes and consequences of intra-specific variation in vertebral number
Authors: Tibblin Petter , Berggren Hanna , Nordahl Oscar , Larsson Per , Forsman Anders
Published: May 2016

Intraspecific variation in vertebral number is taxonomically widespread. Much scientific attention has been directed towards understanding patterns of variation in vertebral number among individuals and between populations, particularly across large spatial scales and in structured environments. However, the relative role of genes, plasticity, selection, and drift as drivers of individual variation and population differentiation remains unknown for most systems. Here, we report on patterns, causes and consequences of variation in vertebral number among and within sympatric subpopulations of pike (Esox lucius). Vertebral number differed among subpopulations, and common garden experiments indicated that this reflected genetic differences. A QST-FST comparison suggested that population differences represented local adaptations driven by divergent selection. Associations with fitness traits further indicated that vertebral counts were influenced both by stabilizing and directional selection within populations. Overall, our study enhances the understanding of adaptive variation, which is critical for the maintenance of intraspecific diversity and species conservation.
Correlating the Energetics and Atomic Motions of the Metal-Insulator Transition of M1 Vanadium Dioxide
Authors: Booth Jamie M. , Drumm Daniel W. , Casey Phil S. , Smith Jackson S. , Seeber Aaron J. , Bhargava Suresh K. , Russo Salvy P.
Published: May 2016

Materials that undergo reversible metal-insulator transitions are obvious candidates for new generations of devices. For such potential to be realised, the underlying microscopic mechanisms of such transitions must be fully determined. In this work we probe the correlation between the energy landscape and electronic structure of the metal-insulator transition of vanadium dioxide and the atomic motions occurring using first principles calculations and high resolution X-ray diffraction. Calculations find an energy barrier between the high and low temperature phases corresponding to contraction followed by expansion of the distances between vanadium atoms on neighbouring sub-lattices. X-ray diffraction reveals anisotropic strain broadening in the low temperature structure’s crystal planes, however only for those with spacings affected by this compression/expansion. GW calculations reveal that traversing this barrier destabilises the bonding/anti-bonding splitting of the low temperature phase. This precise atomic description of the origin of the energy barrier separating the two structures will facilitate more precise control over the transition characteristics for new applications and devices.
Polarization induced two dimensional confinement of carriers in wedge shaped polar semiconductors
Authors: Deb S. , Bhasker H. P. , Thakur Varun , Shivaprasad S. M. , Dhar S.
Published: May 2016

A novel route to achieve two dimensional (2D) carrier confinement in a wedge shaped wall structure made of a polar semiconductor has been demonstrated theoretically. Tapering of the wall along the direction of the spontaneous polarization leads to the development of charges of equal polarity on the two inclined facades of the wall. Polarization induced negative (positive) charges on the facades can push the electrons (holes) inward for a n-type (p-type) material which results in the formation of a 2D electron (hole) gas at the central plane and ionized donors (acceptors) at the outer edges of the wall. The theory shows that this unique mode of 2D carrier confinement can indeed lead to a significant enhancement of carrier mobility. It has been found that the reduced dimensionality is not the only cause for the enhancement of mobility in this case. Ionized impurity scattering, which is one of the major contributer to carrier scattering, is significantly suppressed as the carriers are naturally separated from the ionized centers. A recent experimental finding of very high electron mobility in wedge shaped GaN nanowall networks has been analyzed in the light of this theoretical reckoning.
Magnesium inference screw supports early graft incorporation with inhibition of graft degradation in anterior cruciate ligament reconstruction
Authors: Cheng Pengfei , Han Pei , Zhao Changli , Zhang Shaoxiang , Zhang Xiaonong , Chai Yimin
Published: May 2016

Patients after anterior cruciate ligament (ACL) reconstruction surgery commonly encounters graft failure in the initial phase of rehabilitation. The inhibition of graft degradation is crucial for the successful reconstruction of the ACL. Here, we used biodegradable high-purity magnesium (HP Mg) screws in the rabbit model of ACL reconstruction with titanium (Ti) screws as a control and analyzed the graft degradation and screw corrosion using direct pull-out tests, microCT scanning and histological and immunohistochemical staining. The most noteworthy finding was that tendon graft fixed by HP Mg screws exhibited biomechanical properties substantially superior to that by Ti screws and the relative area of collagen fiber at the tendon-bone interface was much larger in the Mg group, when severe graft degradation was identified in the histological analysis at 3 weeks. Semi-quantitative immunohistochemical results further elucidated that the MMP-13 expression significantly decreased surrounding HP Mg screws with relatively higher Collagen II expression. And HP Mg screws exhibited uniform corrosion behavior without displacement or loosening in the femoral tunnel. Therefore, our results demonstrated that Mg screw inhibited graft degradation and improved biomechanical properties of tendon graft during the early phase of graft healing and highlighted its potential in ACL reconstruction.
Next-generation proteasome inhibitor MLN9708 sensitizes breast cancer cells to doxorubicin-induced apoptosis
Authors: Wang Hao , Yu Yang , Jiang Zheng , Cao Wen-Ming , Wang Zhenyu , Dou Jun , Zhao Yanling , Cui Yunfu , Zhang Hong
Published: May 2016

Doxorubicin (Dox), one of the most effective chemotherapy drug for cancer treatment, is limited by its severe side effects and chemoresistance. Dox induces DNA damage and leads to significant proteomic changes in the cancer cells, which makes the ubiquitin-proteasome system a potential target to enhance the efficacy of Dox therapy. The unsuccessful clinical trials of proteasome inhibitor PS-341 (bortezomib) in solid tumors led to the invention of MLN9708 (ixazomib), an orally bioavailable next-generation proteasome inhibitor with improved pharmacokinetic and pharmacodynamic features. In this preclinical study, we used eight human breast cancer cell lines, which represent the major molecular subtypes of breast cancer, to validate the cytotoxic effects of MLN9708, alone and in combination with Dox. We found that MLN9708 had cytotoxic effects, induced autophagy and MKP-1 expression, and enhanced Dox-induced apoptosis in these cell lines. MLN9708 also enhanced Dox-induced JNK and p38 phosphorylation and inhibited Dox-induced IκBα degradation. Our in vitro results suggest that MLN9708 has antitumor effects in breast cancer and can sensitize breast cancer cells to Dox treatment. This promising combination may be an effective and feasible therapeutic option for treating breast cancer and warrants clinical validation.
Cryopreserved Mesenchymal Stromal Cells Maintain Potency in a Retinal Ischemia/Reperfusion Injury Model: Toward an off-the-shelf Therapy
Authors: Gramlich Oliver W. , Burand Anthony J. , Brown Alex J. , Deutsch Riley J. , Kuehn Markus H. , Ankrum James A.
Published: May 2016

The ability to use mesenchymal stromal cells (MSC) directly out of cryostorage would significantly reduce the logistics of MSC therapy by allowing on-site cryostorage of therapeutic doses of MSC at hospitals and clinics. Such a paradigm would be especially advantageous for the treatment of acute conditions such as stroke and myocardial infarction, which are likely to require treatment within hours after ischemic onset. Recently, several reports have emerged that suggest MSC viability and potency are damaged by cryopreservation. Herein we examine the effect of cryopreservation on human MSC viability, immunomodulatory potency, growth factor secretion and performance in an ischemia/reperfusion injury model. Using modifications of established cryopreservation methods we developed MSC that retain >95% viability upon thawing, remain responsive to inflammatory signals and are able to suppress activated human peripheral blood mononuclear cells. Most importantly, when injected into the eyes of mice 3 hours after the onset of ischemia and 2 hours after the onset of reperfusion, cryopreserved performed as well as fresh MSC to rescue retinal ganglion cells. Thus, our data suggests when viability is maintained throughout the cryopreservation process, MSC retain their therapeutic potency in both in vitro potency assays and an in vivo ischemia/reperfusion model.
Genetic variant in CXCL13 gene is associated with susceptibility to intrauterine infection of hepatitis B virus
Authors: Wan Zhihua , Lin Xiaofang , Li Tongyang , Zhou Aifen , Yang Mei , Hu Dan , Feng Li , Peng Songxu , Fan Linlin , Tu Si , Bin Zhang  , Du Yukai
Published: May 2016

Intrauterine infection of hepatitis B virus (HBV), which accounts for the majority of mother-to-child transmission, is one of the main reasons for the failure of combined immunoprophylaxis against the transmission. Recent studies have identified that genetic background might influence the susceptibility to intrauterine infection of HBV. We conducted this study to investigate the associations between 10 genetic variants in 9 genes (SLC10A1, HLA-DP, HLA-C, CXCR5, CXCL13, TLR3, TLR4, TLR9 and UBE2L3) of mothers and their neonates and HBV intrauterine infection. A significantly decreased risk of HBV intrauterine transmission were found among mothers who carried the rs355687 CT genotypes in CXCL13 gene compared to those with CC genotypes (OR = 0.25, 95% CI, 0.08–0.82, P = 0.022); and a marginally significantly decreased risk was also observed under the dominant model (OR = 0.34, 95% CI, 0.11–1.01, P = 0.052). Besides, neonatal rs3130542 in HLA-C gene was found to be marginally significantly associated with decreased risk of HBV intrauterine infection under the additive model (OR = 0.55, 95% CI, 0.29–1.04, P = 0.064). However, we found no evidence of associations between the remaining 8 SNPs and risk of HBV intrauterine infection among mothers and their neonates. In conclusion, this study suggested that genetic variant in CXCL13 gene was associated with susceptibility to intrauterine infection of HBV.
Proline-rich tyrosine kinase 2 via enhancing signal transducer and activator of transcription 3-dependent cJun expression mediates retinal neovascularization
Authors: Kumar Raj , Singh Nikhlesh K. , Rao Gadiparthi N.
Published: May 2016

Despite the involvement of proline-rich tyrosine kinase 2 (Pyk2) in endothelial cell angiogenic responses, its role in pathological retinal angiogenesis is not known. In the present study, we show that vascular endothelial growth factor A (VEGFA) induces Pyk2 activation in mediating human retinal microvascular endothelial cell (HRMVEC) migration, sprouting and tube formation. Downstream to Pyk2, VEGFA induced signal transducer and activator of transcription 3 (STAT3) activation and cJun expression in the modulation of HRMVEC migration, sprouting and tube formation. Consistent with these observations, hypoxia induced activation of Pyk2-STAT3-cJun signaling axis and siRNA-mediated downregulation of Pyk2, STAT3 or cJun levels substantially inhibited hypoxia-induced retinal endothelial cell proliferation, tip cell formation and neovascularization. Together, these observations suggest that activation of Pyk2-mediated STAT3-cJun signaling is required for VEGFA-induced HRMVEC migration, sprouting and tube formation in vitro and hypoxia-induced retinal endothelial cell proliferation, tip cell formation and neovascularization in vivo.