bluuebunny/crossref_metadata_2025 huggingface dataset:
Synchrotron X‐Ray Scanning Tunneling Microscopy: Fingerprinting Near to Far Field Transitions on Cu(111) Induced by Synchrotron Radiation
Authors: Rose Volker , Wang Kangkang , Chien TeYu , Hiller Jon , Rosenmann Daniel , Freeland John W. , Preissner Curt , Hla Saw‐Wai
Published: March 2013

The combination of the high spatial resolution of scanning tunneling microscopy with the chemical and magnetic contrast provided by synchrotron X‐rays has the potential to allow a unique characterization of advanced functional materials. While the scanning probe provides the high spatial resolution, synchrotron X‐rays that produce photo‐excitations of core electrons add chemical and magnetic contrast. However, in order to realize the method's full potential it is essential to maintain tunneling conditions, even while high brilliance X‐rays irradiate the sample surface. Different from conventional scanning tunneling microscopy, X‐rays can cause a transition of the tip out of the tunneling regime. Monitoring the reaction of the z‐piezo (the element that controls the tip to sample separation) alone is not sufficient, because a continuous tip current is obtained. As a solution, an unambiguous and direct way of fingerprinting such near to far field transitions of the tip that relies on the simultaneous analysis of the X‐ray‐induced tip and sample current is presented. This result is of considerable importance because it opens the path to the ultimate resolution in X‐ray enhanced scanning tunneling microscopy.
Nanomaterial‐Based Fluorescent DNA Analysis: A Comparative Study of the Quenching Effects of Graphene Oxide, Carbon Nanotubes, and Gold Nanoparticles
Authors: Li Fan , Pei Hao , Wang Lihua , Lu Jianxin , Gao Jimin , Jiang Bowei , Zhao Xingchun , Fan Chunhai
Published: March 2013

A variety of nanomaterials have shown extraordinarily high quenching ability toward a broad range of fluorophores. Recently, there has been intense interest in developing new tools for fluorescent DNA analysis in solution or inside the cell based on this property, and by exploiting interactions between these nanoscale “superquenchers” and DNA molecules in the single‐stranded (ss‐) or double‐stranded (ds‐) forms. Here, a comparative study on the nanoqueching effects is performed by using a series of nanomaterials with different dimensions, i.e., gold nanoparticles (AuNPs, 0D), carbon nanotubes (CNTs, 1D), and graphene oxide (GO, 2D). The quenching efficiency, kinetics, differentiation ability, and influencing factors such as concentration and ionic strength are studied. Interestingly, GO exhibits superior quenching abilities to the other two materials in both the quenching efficiency and kinetics. As a result, a GO‐based fluorescent sensor, designed in a simple mix‐and‐detect format, can detect concentrations of DNA as low as 0.2 nM, which is better than either CNTs or AuNPs by an order of magnitude. This sensor can also differentiate single‐base mismatches much better than either CNTs‐ or AuNPs‐ based sensors. This study paves the way to better choice of nanomaterials for bioanalysis and elaborate design of biosensors for both in vitro diagnosis and in vivo bioimaging.
Nano‐Graphene Oxide: A Potential Multifunctional Platform for Cancer Therapy
Authors: Gonçalves Gil , Vila Mercedes , Portolés María‐Teresa , Vallet‐Regi María , Gracio José , Marques Paula Alexandrina A. P.
Published: March 2013

Nano‐GO is a graphene derivative with a 2D atomic layer of sp2 bonded carbon atoms in hexagonal conformation together with sp3 domains with carbon atoms linked to oxygen functional groups. The supremacy of nano‐GO resides essentially in its own intrinsic chemical and physical structure, which confers an extraordinary chemical versatility, high aspect ratio and unusual physical properties. The chemical versatility of nano‐GO arises from the oxygen functional groups on the carbon structure that make possible its relatively easy functionalization, under mild conditions, with organic molecules or biological structures in covalent or non‐covalent linkage. The synergistic effects resulting from the assembly of well‐defined structures at nano‐GO surface, in addition to its intrinsic optical, mechanical and electronic properties, allow the development of new multifunctional hybrid materials with a high potential in multimodal cancer therapy. Herein, a comprehensive review of the fundamental properties of nano‐GO requirements for cancer therapy and the first developments of nano‐GO as a platform for this purpose is presented.
The “Secret” in Secretions: Methodological Considerations in Deciphering Primate Olfactory Communication
Authors: DREA CHRISTINE M. , BOULET MARYLÈNE , DELBARCO‐TRILLO JAVIER , GREENE LYDIA K. , SACHA CAITLIN R. , GOODWIN THOMAS E. , DUBAY GEORGE R.
Published: March 2013

Olfactory communication in primates is gaining recognition; however, studies on the production and perception of primate scent signals are still scant. In general, there are five tasks to be accomplished when deciphering the chemical signals contained in excretions and secretions: (1) obtaining the appropriate samples; (2) extracting the target organic compounds from the biological matrix; (3) separating the extracted compounds from one another (by gas chromatography, GC or liquid chromatography, LC); (4) identifying the compounds (by mass spectrometry, MS and associated procedures); and (5) revealing biologically meaningful patterns in the data. Ultimately, because some of the compounds identified in odorants may not be relevant, associated steps in understanding signal function involve verifying the perception or biological activity of putative semiochemicals via (6) behavioral bioassays or (7) receptor response studies. This review will focus on the chemical analyses and behavioral bioassays of volatile, primate scent signals. Throughout, we highlight the potential pitfalls of working with highly complex, chemical matrices and suggest ways for minimizing problems. A recurring theme in this review is that multiple approaches and instrumentation are required to characterize the full range of information contained in the complex mixtures that typify primate or, indeed, many vertebrate olfactory cues. Only by integrating studies of signal production with those verifying signal perception will we better understand the function of olfactory communication. Am. J. Primatol. 75:621–642, 2013. © 2013 Wiley Periodicals, Inc.
Population Density of Red Langurs in Sabangau Tropical Peat‐Swamp Forest, Central Kalimantan, Indonesia
Authors: EHLERS SMITH DAVID A. , EHLERS SMITH YVETTE C.
Published: March 2013

Because of the large‐scale destruction of Borneo's rainforests on mineral soils, tropical peat‐swamp forests (TPSFs) are increasingly essential for conserving remnant biodiversity, particularly in the lowlands where the majority of habitat conversion has occurred. Consequently, effective strategies for biodiversity conservation are required, which rely on accurate population density and distribution estimates as a baseline. We sought to establish the first population density estimates of the endemic red langur (Presbytis rubicunda) in Sabangau TPSF, the largest remaining contiguous lowland forest‐block on Borneo. Using Distance sampling principles, we conducted line transect surveys in two of Sabangau's three principle habitat sub‐classes and calculated group density at 2.52 groups km−2(95% CI 1.56–4.08) in the mixed‐swamp forest sub‐class. Based on an average recorded group size of 6.95 individuals, population density was 17.51 ind km−2, the second highest density recorded in this species. The accessible area of the tall‐interior forest, however, was too disturbed to yield density estimates representative of the entire sub‐class, andP. rubicundawas absent from the low‐pole forest, likely as a result of the low availability of the species' preferred foods. This absence in 30% of Sabangau's total area indicates the importance of in situ population surveys at the habitat‐specific level for accurately informing conservation strategies. We highlight the conservation value of TPSFs forP. rubicundagiven the high population density and large areas remaining, and recommend 1) quantifying the response ofP. rubicundato the logging and burning of its habitats; 2) surveying degraded TPSFs for viable populations, and 3) effectively delineating TPSF sub‐class boundaries from remote imagery to facilitate population estimates across the wider peat landscape, given the stark contrast in densities found across the habitat sub‐classes of Sabangau. Am. J. Primatol. 75:837–847, 2013. © 2013 Wiley Periodicals, Inc.
Indian ocean crossroads: Human genetic origin and population structure in the maldives
Authors: Pijpe Jeroen , de Voogt Alex , van Oven Mannis , Henneman Peter , van der Gaag Kristiaan J. , Kayser Manfred , de Knijff Peter
Published: March 2013

The Maldives are an 850 km‐long string of atolls located centrally in the northern Indian Ocean basin. Because of this geographic situation, the present‐day Maldivian population has potential for uncovering genetic signatures of historic migration events in the region. We therefore studied autosomal DNA‐, mitochondrial DNA‐, and Y‐chromosomal DNA markers in a representative sample of 141 unrelated Maldivians, with 119 from six major settlements. We found a total of 63 different mtDNA haplotypes that could be allocated to 29 mtDNA haplogroups, mostly within the M, R, and U clades. We found 66 different Y‐STR haplotypes in 10 Y‐chromosome haplogroups, predominantly H1, J2, L, R1a1a, and R2. Parental admixture analysis for mtDNA‐ and Y‐haplogroup data indicates a strong genetic link between the Maldive Islands and mainland South Asia, and excludes significant gene flow from Southeast Asia. Paternal admixture from West Asia is detected, but cannot be distinguished from admixture from South Asia. Maternal admixture from West Asia is excluded. Within the Maldives, we find a subtle genetic substructure in all marker systems that is not directly related to geographic distance or linguistic dialect. We found reduced Y‐STR diversity and reduced male‐mediated gene flow between atolls, suggesting independent male founder effects for each atoll. Detected reduced female‐mediated gene flow between atolls confirms a Maldives‐specific history of matrilocality. In conclusion, our new genetic data agree with the commonly reported Maldivian ancestry in South Asia, but furthermore suggest multiple, independent immigration events and asymmetrical migration of females and males across the archipelago. Am J Phys Anthropol 151:58–67, 2013. © 2013 Wiley Periodicals, Inc.
JC virus antibody status underestimates infection rates
Authors: Berger Joseph R. , Houff Sidney A. , Gurwell Julie , Vega Nubia , Miller Craig S. , Danaher Robert J.
Published: March 2013

Objective

JC virus (JCV) seropositivity is a risk factor for progressive multifocal leukoencephalopathy (PML) in patients on natalizumab. Accordingly, the JCV serological antibody test is of paramount importance in determining disease risk.

Methods

We tested the accuracy of the JCV serum antibody test by comparing the results of JCV serology to JCV viruria and viremia in 67 patients enrolled in a single‐center, retrospective cohort study. Bodily fluids (urine and blood) were assessed for JCV DNA by real time quantitative polymerase chain reaction 6 to 47 months (mean = 26.1 months) before JCV antibody testing. In 10 individuals, blood and urine samples were obtained on 2 separate occasions at 6‐month intervals.

Results

Forty (59.7%) of the 67 patients were JCV seropositive. Of 27 JCV seronegative patients, 10 (37%) had JCV viruria. Urine JCV DNA copy numbers were significantly higher in the seropositive group (mean log copy number = 5.93, range = 1.85–9.21) than the seronegative group (mean log copy number = 2.41, range = 1.85–5.43; p = 0.0026). Considering all body fluid test results, 50 (74.6%) of the 67 patients were previously infected with JCV.

Interpretation

The false‐negative rate of the JCV serology in this study was 37%; therefore, JCV serostatus does not appear to identify all patients infected with JCV. Thus, a negative JCV antibody result should not be conflated with absence of JCV infection. This discordance may be important in understanding JCV biology, risk for PML, and PML pathogenesis. Ann Neurol 2013;74:84–90
G51D α‐synuclein mutation causes a novel Parkinsonian–pyramidal syndrome
Authors: Lesage Suzanne , Anheim Mathieu , Letournel Franck , Bousset Luc , Honoré Aurélie , Rozas Nelly , Pieri Laura , Madiona Karine , Dürr Alexandra , Melki Ronald , Verny Christophe , Brice Alexis ,   for the French Parkinson's Disease Genetics Study Group
Published: March 2013

Objective

To date, 3 rare missense mutations in the SNCA (α‐synuclein) gene and the more frequent duplications or triplications of the wild‐type gene are known to cause a broad array of clinical and pathological symptoms in familial Parkinson disease (PD). Here, we describe a French family with a parkinsonian–pyramidal syndrome harboring a novel heterozygous SNCA mutation.

Methods

Whole exome sequencing of DNA from 3 patients in a 3‐generation pedigree was used to identify a new PD‐associated mutation in SNCA. Clinical and pathological features of the patients were analyzed. The cytotoxic effects of the mutant and wild‐type proteins were assessed by analytical ultracentrifugation, thioflavin T binding, transmission electron microscopy, cell viability assay, and caspase‐3 activation.

Results

We identified a novel SNCA G51D (c.152 G>A) mutation that cosegregated with the disease and was absent from controls. G51D was associated with an unusual PD phenotype characterized by early disease onset, moderate response to levodopa, rapid progression leading to loss of autonomy and death within a few years, marked pyramidal signs including bilateral extensor plantar reflexes, occasionally spasticity, and frequently psychiatric symptoms. Pathological lesions predominated in the basal ganglia and the pyramidal tracts and included fine, diffuse cytoplasmic inclusions containing phospho‐α‐synuclein in superficial layers of the cerebral cortex, including the entorhinal cortex. Functional studies showed that G51D α‐synuclein oligomerizes more slowly and its fibrils are more toxic than those of the wild‐type protein.

Interpretation

We have identified a novel SNCA G51D mutation that causes a form of PD with unusual clinical, neuropathological, and biochemical features. Ann Neurol 2013;73:459–471
Could artificial structures such as fish passes facilitate the establishment and spread of the ‘killer shrimp’ Dikerogammarus villosus (Crustacea: Amphipoda) in river systems?
Authors: Macneil Calum , Platvoet Dirk
Published: March 2013

Linkages between habitat structure, invasibility and direct species interactions were examined in a Central European river system, the Schipbeek in the Netherlands, invaded by the ‘killer shrimp’ amphipod Dikerogammarus villosus. The invader's arrival in other fresh waters is linked to declines in macroinvertebrate biodiversity, with previous studies indicating that the invader's impacts may be mediated by habitat heterogeneity and substrate type.

Using an extensive 50 km field survey, potential habitat factors influencing distribution were identified. Of 12 sites surveyed, two contained fish ‘passes’ (instream sections creating faster flows via concrete structures covered in cemented rocks). It was only in these sites that D. villosus was found and then only in the fish pass areas, as opposed to the surrounding river, which, like the remaining 10 sites of the survey, was characterized by sluggish flows and a muddy/silty substrate. Gammarus roeselii was the numerically dominant amphipod in these latter areas, with no D. villosus being detected. A repeated survey more than 2 years later, revealed the same distribution pattern.

Within both fish pass areas, D. villosus relative abundance was highest in faster flowing, less macrophyte dense patches, with the opposite true for G. roeselii. D. villosus numerical abundance decreased with increasing macrophyte cover in both passes.

A transplant experiment indicated high survivorship of D. villosus outside fish pass areas and showed that slow‐flowing watercourses with mud/silt substrates, previously deemed ‘unsuitable’, are not effective barriers to D. villosus spreading to more ‘suitable’, faster, rocky substrate watercourses.

We recommend that when the location and cost‐benefit analysis of instream rehabilitation structures, such as fish passes, is being considered, attention must be paid to the risk of hastening the spread of this invader. We also recommend that when monitoring programmes are designed for D. villosus in newly invaded regions, instream artificial structures should be included as part of the survey.

Copyright © 2013 John Wiley & Sons, Ltd.
Mitochondrial DNA variation of the bocachico Prochilodus magdalenae (Characiformes, Prochilodontidae) in the Magdalena River Basin, Colombia
Authors: Aguirre‐Pabón Juan , Narváez Barandica Juan , Castro García Lyda
Published: March 2013

The bocachico Prochilodus magdalenae is a freshwater migratory species of great importance for conservation in Colombia. The populations of this fish have been seriously threatened in the last decade, and there is limited knowledge of its genetic conditions.

In order to evaluate the genetic structure of P. magdalenae in the Magdalena River basin and some tributaries, the mitochondrial DNA control region was analysed in samples selected from 20 sites.

In total, 189 polymorphic sites were detected on a sequence of 500 bp of the control region among 292 individuals, defining 233 haplotypes from which 88.41% were private. Genetic diversity was high (HD = 0.997 and π = 0.0303), neither the analysis of molecular variance, the Φst statistic, nor the Mantel test values revealed significant differences of population subdivision in any of the hierarchical levels. The tests of neutrality and mismatch distribution detected a population expansion in the Middle Pleistocene.

Results showed that P. magdalenae forms a large panmictic population in the basin of the Magdalena River. A wide migratory capacity, the absence of geographical barriers and not enough time to accumulate genetic variation are likely reasons for the genetic homogeneity found in this species.

Copyright © 2013 John Wiley & Sons, Ltd.
Can accidental introductions of non‐native species be prevented by fish stocking audits?
Authors: Davies Gareth D. , Gozlan Rodolphe E. , Robert Britton J.
Published: March 2013

Accidental introductions of non‐native species into aquatic environments often result in invasive populations that cause substantial conservation concerns. They account for 8% of all fish introductions and often occur when fish consignments are intentionally released into the wild (‘stocked’) but are unknowingly contaminated with a ‘hitch‐hiking’ species that is also released.

This study tested the efficacy of a fish stocking audit procedure in preventing the introduction of a model hitch‐hiking fish (Pseudorasbora parva) within a batch of model native fish (Rutilus rutilus). It was tested in relation to different P. parva contamination levels (1, 5, 10, 20%), auditor expertise (Expert, Intermediate, Novice) and search effort.

There was considerable variability in the detection thresholds among contamination levels, auditor experience and search effort; false‐negative recordings reduced as all these parameters increased. Probability of P. parva detection (POD, 0 to 1) showed that at the lowest search effort, POD was greater than 0.80 for Expert auditors only when contamination levels exceeded 10%. At the highest search effort, POD was greater than 0.80 at the 1% contamination level for Experts, but was at 3 and 8% contamination for Intermediates and Novices.

Thus, while small non‐native fishes are at risk of being accidentally introduced owing to their difficulty of detection in stocking consignments, an effective audit procedure using experienced auditors and high search effort reduces this risk. Implementation should help prevent subsequent invasions, protecting native species from their adverse ecological consequences.

Copyright © 2013 John Wiley & Sons, Ltd.
Synthesis and Biological Evaluation of Some 1,2‐Disubstituted Benzimidazole Derivatives as New Potential Anticancer Agents
Authors: Yurttaş Leyla , Demirayak Şeref , Çiftçi Gülşen A. , Yıldırım Şafak Ulusoylar , Kaplancıklı Zafer A.
Published: March 2013

The synthesis of some new 1‐(2‐aryl‐2‐oxoethyl)‐2‐[(morpholine‐4‐yl)thioxomethyl]benzimidazole derivatives and investigation of their anticancer activities were the aims of this work. 2‐(Chloromethyl)benzimidazole compound was reacted with sulfur and morpholine via Willgerodt–Kindler reaction to give 2‐[(morpholine‐4‐yl)thioxomethyl]benzimidazole. Then, the obtained compound was reacted with appropriate α‐bromoacetophenone derivatives in the presence of potassium carbonate to give the final products. Structure elucidation of the final compounds was achieved by FT‐IR, 1H NMR spectroscopy and MS spectrometry. The anticancer activities of the final compounds were evaluated by MTT assay, BrdU method, and flow cytometric analysis on C6, MCF‐7, and A549 tumor cells. Most of the synthesized compounds exhibited considerable selectivity against the MCF‐7 and C6 cell lines.
Measuring the value of health query translation: An analysis by user language proficiency
Authors: Lopes Carla Teixeira , Ribeiro Cristina
Published: March 2013

English is by far the most used language on the web. In some domains, the existence of less content in the users' native language may not be problematic and even help to cope with the information overload. Yet, in domains such as health, where information quality is critical, a larger quantity of information may mean easier access to higher quality content. Query translation may be a good strategy to access content in other languages, but the presence of medical terms in health queries makes the translation process more difficult, even for users with very good language proficiencies. In this study, we evaluate how translating a health query affects users with different language proficiencies. We chose English as the non‐native language because it is a widely spoken language and it is the most used language on the web. Our findings suggest that non‐English–speaking users having at least elementary English proficiency can benefit from a system that suggests English alternatives for their queries, or automatically retrieves English content from a non‐English query. This awareness of the user profile results in higher precision, more accurate medical knowledge, and better access to high‐quality content. Moreover, the suggestions of English‐translated queries may also trigger new health search strategies.
Sirenomelia: A new type, Showing VACTERL Association with thomas syndrome and a review of literature
Authors: Lhuaire Martin , Jestin Agnès , Boulagnon Camille , Loock Mélanie , Doco‐Fenzy Martine , Gaillard Dominique , Diebold Marie‐Danièle , Avisse Claude , Labrousse Marc
Published: March 2013

Sirenomelia or “mermaid syndrome” is a rare congenital anomaly known since antiquity. This congenital anomaly is defined as a polymalformative syndrome that associates major muscle and skeleton abnormalities (unique lower limbs) with visceral abnormalities (unilateral or bilateral renal agenesis, anomalies of the abdominal vascularisation). This phenotype, typical of sirenomelia syndrome, may be more or less severe. The pathogenic mechanisms of this syndrome are still debated and its etiology remains unknown. We report here a new type of sirenomelia that we observed in a fetus belonging to the collection of the Department of Anatomy of Reims, which led us to perform a comprehensive review of the literature on the subject: this type has never been reported and cannot be classified according to the Stocker and Heifetz classification. Moreover, this case also presents a VACTERL association with Thomas syndrome. Birth Defects Research (Part A) 97:123–132, 2013. © 2013 Wiley Periodicals, Inc.
Difference in the structures of alanine tri‐ and tetra‐peptides with antiparallel β‐sheet assessed by X‐ray diffraction, solid‐state NMR and chemical shift calculations by GIPAW
Authors: Asakura Tetsuo , Yazawa Koji , Horiguchi Kumiko , Suzuki Furitsu , Nishiyama Yusuke , Nishimura Katsuyuki , Kaji Hironori
Published: March 2013

Alanine oligomers provide a key structure for silk fibers from spider and wild silkworms.We report on structural analysis of l‐alanyl‐l‐alanyl‐l‐alanyl‐l‐alanine (Ala)4 with anti‐parallel (AP) β‐structures using X‐ray and solid‐state NMR. All of the Ala residues in the (Ala)4 are in equivalent positions, whereas for alanine trimer (Ala)3 there are two alternative locations in a unit cell as reported previously (Fawcett and Camerman, Acta Cryst., 1975, 31, 658–665). (Ala)4 with AP β‐structure is more stable than AP‐(Ala)3 due to formation of the stronger hydrogen bonds. The intermolecular structure of (Ala)4 is also different from polyalanine fiber structure, indicating that the interchain arrangement of AP β‐structure changes with increasing alanine sequencelength. Furthermore the precise 1H positions, which are usually inaccesible by X‐ray diffraction method, are determined by high resolution 1H solid state NMR combined with the chemical shift calculations by the gauge‐including projector augmented wave method. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 13–20, 2014.
Bioanalytical method development, validation and quantification of dorsomorphin in rat plasma by LC‐MS/MS
Authors: Karthikeyan K. , Mahat Mahamad Yunnus A. , Chandrasekaran S. , Gopal K. , Franklin P. X. , Sivakumar Balasubramanian Jaganatha , Singh Gajendra , Narayanan Shridhar , Gopalan B. , Khan Ansar A.
Published: March 2013

The present investigation describes the development and validation of a sensitive liquid chromatography–mass spectrometry/mass spectrometry (LC‐MS/MS) method for the estimation of dorsomorphin in rat plasma. A sensitive LC‐MS/MS method was developed using multiple reaction monitoring mode, with the transition of m/z (Q1/Q3) 400.2/289.3 for dorsomorphin and m/z (Q1/Q3) 306.2/236.3 for zaleplon. Chromatographic separation was achieved on a reverse phase Agilent XDB C18 column (100 × 4.6 mm, 5 µm). The mobile phase consisted of acetonitrile and 5 mm ammonium acetate buffer (pH 6.0) 90:10 v/v, at a flow rate of 0.8 mL/min. The effluence was ionized in positive ion mode by electrospray ionization (ESI) and quantitated by mass spectrometry. The retention times of dorsomorphin and internal standard were found to be 2.13 and 1.13 min, respectively. Mean extraction recovery of dorsomorphin and internal standard in rat plasma was above 80%. Dorsomorphin calibration curve in rat plasma was linear (r2 ≥ 0.99) ranging from 0.005 to 10 µg/mL. Inter‐day and intra‐day precision and accuracy were found to be within 85–115% (coefficient of variation). This method was successfully applied for evaluation of the oral pharmacokinetic profile of dorsomorphin in male Wistar rats. Copyright © 2013 John Wiley & Sons, Ltd.
Synthesis and application of a chiral ionic liquid functionalized β‐cyclodextrin as a chiral selector in capillary electrophoresis
Authors: Yu Jia , Zuo Lihua , Liu Hongjiao , Zhang Lijuan , Guo Xingjie
Published: March 2013

A novel chiral ionic liquid functionalized β‐cyclodextrin, 6‐O‐2‐hydroxpropyltrimethylammonium‐β‐cyclodextrin tetrafluoroborate ([HPTMA‐β‐CD][BF4]), was synthesized and used as a chiral selector in capillary electrophoresis. [HPTMA‐β‐CD][BF4] not only increased the solubility in aqueous buffer in comparison with the parent compound, but also provided a stable reversal electroosmotic flow, and the enantioseparation of eight chiral drugs was examined in phosphate buffer containing [HPTMA‐β‐CD][BF4] as the chiral selector. The effects of the [HPTMA‐β‐CD][BF4] concentration and the background electrolyte pH were studied. Moreover, the chiral separation abilities of β‐CD and [HPTMA‐β‐CD][BF4] were compared and possible mechanisms for the chiral recognition of [HPTMA‐β‐CD][BF4] are discussed. Copyright © 2013 John Wiley & Sons, Ltd.
Dopamine‐transporter levels drive striatal responses to apomorphine in Parkinson's disease
Authors: Passamonti Luca , Salsone Maria , Toschi Nicola , Cerasa Antonio , Giannelli Marco , Chiriaco Carmelina , Cascini Giuseppe Lucio , Fera Francesco , Quattrone Aldo
Published: March 2013

Dopaminergic therapy in Parkinson's disease (PD) can improve some cognitive functions while worsening others. These opposite effects might reflect different levels of residual dopamine in distinct parts of the striatum, although the underlying mechanisms remain poorly understood. We used functional magnetic resonance imaging (fMRI) to address how apomorphine, a potent dopamine agonist, influences brain activity associated with working memory in PD patients with variable levels of nigrostriatal degeneration, as assessed via dopamine‐transporter (DAT) scan. Twelve PD patients underwent two fMRI sessions (Off‐, On‐apomorphine) and one DAT‐scan session. Twelve sex‐, age‐, and education‐matched healthy controls underwent one fMRI session. The core fMRI analyses explored: (1) the main effect of group; (2) the main effect of treatment; and (3) linear and nonlinear interactions between treatment and DAT levels. Relative to controls, PD‐Off patients showed greater activations within posterior attentional regions (e.g., precuneus). PD‐On versus PD‐Off patients displayed reduced left superior frontal gyrus activation and enhanced striatal activation during working‐memory task. The relation between DAT levels and striatal responses to apomorphine followed an inverted‐U‐shaped model (i.e., the apomorphine effect on striatal activity in PD patients with intermediate DAT levels was opposite to that observed in PD patients with higher and lower DAT levels). Previous research in PD demonstrated that the nigrostriatal degeneration (tracked via DAT scan) is associated with inverted‐U‐shaped rearrangements of postsynaptic D2‐receptors sensitivity. Hence, it can be hypothesized that individual differences in DAT levels drove striatal responses to apomorphine via D2‐receptor‐mediated mechanisms.
Hybrid liposomes inhibit tumor growth and lung metastasis of murine osteosarcoma cells
Authors: Kitajima Hideki , Komizu Yuji , Ichihara Hideaki , Goto Koichi , Ueoka Ryuichi
Published: March 2013

Antitumor effects of hybrid liposomes (HL) composed of l‐α‐dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene(23) dodecyl ether (C12(EO)23) on the metastatic growth of murine osteosarcoma (LM8) cells were investigated in vitro and in vivo. Remarkable inhibitory effects of HL‐23 on the growth of LM8 cells were obtained through the induction of apoptotic cell death in vitro. It was also indicated that HL‐23 should dramatically suppress the invasion of LM8 cells and the formation of filopodia on the cell surface in vitro. Furthermore, significantly high therapeutic effects were observed in the homograft mouse models of LM8 cells with lung metastasis after the treatment with HL‐23 in vivo. That is, the histological analysis demonstrated that the primary tumor growth of LM8 cells implanted subcutaneously into the mice was inhibited along with the induction of apoptosis. In addition, it was found that HL‐23 significantly decreased the lung metastasis of LM8 cells in the mouse models through the inhibition of primary tumor invasion. These results suggest that HL‐23 could be a novel agent for the chemotherapy of osteosarcoma.
T‐LAK cell‐originated protein kinase is essential for the proliferation of hepatocellular carcinoma SMMC‐7721 cells
Authors: Chen Fang , Li Ruwei , Wang Chenji , Cao Lihuan , Wang Yingli , Yu Long
Published: March 2013

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and typically has poor prognosis. Like most cancers, altered gene expression was always associated with the induction and maintenance of HCC. Here, we reported that the expression level of T‐LAK cell‐originated protein kinase (TOPK) is significantly up‐regulated in human HCC samples and cell lines. The suppression of TOPK by short hairpin RNA in HCC cell line SMMC‐7721 caused cell cycle arrest and reduced cell growth and colony formation ability. Moreover, the tumor formation ability of the TOPK‐suppression cells was significantly impaired compared with the control cells in nude mice. In addition, the knockdown expression of TOPK reduced the AKT phosphorylation. Taken together, we unveiled a novel role of TOPK which acts as an important positive regulator in human HCC cell proliferation. Copyright © 2013 John Wiley & Sons, Ltd.
Bridging the gap between metabolic profile determination and visualization in neurometabolic disorders: a multivariate analysis of proton magnetic resonance in vivo spectra
Authors: Skorupa Agnieszka , Jamroz Ewa , Paprocka Justyna , Sokół Maria , Wicher Magdalena , Kiełtyka Aleksandra
Published: March 2013

The purpose of this work was to check the degree of overlap between rare inborn errors of metabolism and other neurological disorders using principal component analysis of proton magnetic resonance spectroscopy (1H MRS) in vivo data. We examined 60 patients (median age of 22 months). Fourteen of them were diagnosed with neurometabolic disorders (three cases of metachromatic leukodystrophy, two cases of Canavan disease, two cases of megalencephalic leukoencephalopathy with subcortical cysts, three cases of mitochondrial cytopathy, one case of nonketotic hyperglycinemia, one case of globoid leukodystrophy, one case of congenital disorders of glycosylation, and one case of ethylmalonic encephalopathy). The remaining 46 patients were diagnosed with epilepsy, cerebral palsy, and developmental delay. Results obtained from principal component analysis of complete unresolved 1H MRS in vivo spectra were interpreted parallelly with LCModel‐derived metabolite levels. The main attention was paid to the following metabolites: N‐acetylaspartate, glutamate + glutamine, creatine, choline, myo‐inositol signal with an uncertain contribution of glycine, and glucose. 1H MRS in vivo coupled with multivariate analysis is an efficient tool in visualization of metabolic abnormalities in several inborn errors of metabolism (metachromatic leukodystrophy, globoid leukodystrophy, megalencephalic leukoencephalopathy with subcortical cysts, and Canavan disease). Copyright © 2013 John Wiley & Sons, Ltd.
Direct Evidence of Significantly Different Chemical Behavior and Excited‐State Dynamics of 1,7‐ and 1,6‐Regioisomers of Pyrrolidinyl‐Substituted Perylene Diimide
Authors: Dubey Rajeev K. , Niemi Marja , Kaunisto Kimmo , Efimov Alexander , Tkachenko Nikolai V. , Lemmetyinen Helge
Published: March 2013

Novel bay‐functionalized perylene diimides with additional substitution sites close to the perylene core have been prepared by the reaction between 1,7(6)‐dibromoperylene diimide 6 (dibromo‐PDI) and 2‐(benzyloxymethyl)pyrrolidine 5. Distinct differences in the chemical behaviors of the 1,7‐ and 1,6‐regioisomers have been discerned. While the 1,6‐dibromo‐PDI produced the corresponding 1,6‐bis‐substituted derivative more efficiently, the 1,7‐dibromo‐PDI underwent predominant mono‐debromination, yielding a mono‐substituted PDI along with a small amount of the corresponding 1,7‐bis‐substituted compound. By varying the reaction conditions, a controlled stepwise bis‐substitution of the bromo substituents was also achieved, allowing the direct synthesis of asymmetrical 1,6‐ and 1,7‐PDIs. The compounds were isolated as individual regioisomers. Fullerene (C60) was then covalently linked at the bay region of the newly prepared PDIs. In this way, two separate sets of perylene diimide–fullerene dyads, namely single‐bridged (SB‐1,7‐PDI‐C60 and SB‐1,6‐PDI‐C60) and double‐bridged (DB‐1,7‐PDI‐C60 and DB‐1,6‐PDI‐C60), were synthesized. The fullerene was intentionally attached at the bay region of the PDI to achieve close proximity of the two chromophores and to ensure an efficient photoinduced electron transfer. A detailed study of the photodynamics has revealed that photoinduced electron transfer from the perylene diimide chromophore to the fullerene occurs in all four dyads in polar benzonitrile, and also occurs in the single‐bridged dyads in nonpolar toluene. The process was found to be substantially faster and more efficient in the dyads containing the 1,7‐regioisomer, both for the singly‐ and double‐bridged molecules. In the case of the single‐bridged dyads, SB‐1,7‐PDI‐C60 and SB‐1,6‐PDI‐C60, different relaxation pathways of their charge‐separated states have been discovered. To the best of our knowledge, this is the first observation of photoinduced electron transfer in PDI‐C60 dyads in a nonpolar medium.
Regioselective Synthesis and Photophysical and Electrochemical Studies of 20‐Substituted Cyanine Dye–Purpurinimide Conjugates: Incorporation of NiII into the Conjugate Enhances its Tumor‐Uptake and Fluorescence‐Imaging Ability
Authors: Ethirajan Manivannan , Chen Ping , Ohulchanskyy Tymish Y. , Goswami Lalit N. , Gupta Anurag , Srivatsan Avinash , Dobhal Mahabeer P. , Missert Joseph R. , Prasad Paras N. , Kadish Karl M. , Pandey Ravindra K.
Published: March 2013

We report herein a simple and efficient approach to the synthesis of a variety of meso‐substituted purpurinimides. The reaction of meso‐substituted purpurinimide with N‐bromosuccinimide regioselectively introduced a bromo functionality at the 20‐position, which on further reaction with a variety of boronic acids under Suzuki reaction conditions yielded the corresponding meso‐substituted analogues. Interestingly, the free base and the metalated analogues showed remarkable differences in photosensitizing efficacy (PDT) and tumor‐imaging ability. For example, the free‐base conjugate showed significant in vitro PDT efficacy, but limited tumor avidity in mice bearing tumors, whereas the corresponding NiII derivative did not produce any cell kill, but showed excellent tumor‐imaging ability at a dose of 0.3 μmol kg−1 at 24, 48, and 72 h post‐injection. The limited PDT efficacy of the NiII analogue could be due to its inability to produce singlet oxygen, a key cytotoxic agent required for cell kill in PDT. Based on electrochemical and spectroelectrochemical data in DMSO, the first one‐electron oxidation (0.52 V vs. SCE) and the first one‐electron reduction (−0.57–0.67 V vs. SCE) of both the free base and the corresponding NiII conjugates are centered on the cyanine dye, whereas the second one‐electron reduction (−0.81 V vs. SCE) of the two conjugates is assigned to the purpurinimide part of the molecule. Reduction of the cyanine dye unit is facile and occurs prior to reduction of the purpurinimide group, which suggests that the cyanine dye unit as an oxidant could be the driving force for quenching of the excited triplet state of the molecules. An interaction between the cyanine dye and the purpurinimide group is clearly observed in the free‐base conjugate, which compares with a negligible interaction between the two functional groups in the NiII conjugate. As a result, the larger HOMO–LUMO gap of the free‐base conjugate and the corresponding smaller quenching constant is a reason to decrease the intramolecular quenching process and increase the production of singlet oxygen to some degree.
Strong Morphological Effect of Mn3O4 Nanocrystallites on the Catalytic Activity of Mn3O4 and Au/Mn3O4 in Benzene Combustion
Authors: Fei Zhao‐Yang , Sun Bo , Zhao Liang , Ji Wei‐Jie , Au Chak‐Tong
Published: March 2013

Gold nanoparticles (3–4 nm) were deposited on Mn3O4 nanocrystallites with three distinct morphologies (cubic, hexagonal, and octahedral). The resulting structures were characterized, and their activities for benzene combustion were evaluated. The dominant exposed facets for the three kinds of Mn3O4 polyhedrons show the activity order: (103)≈(200)>(101). A similar activity order was derived for the interfaces between the Au and the Mn3O4 facet: Au/(200)≈Au/(103)>Au/(101). The metal–support interactions between the Au nanoclusters and specific facets of the Mn3O4 polyhedrons lead to a unique interfacial synergism in which the electronic modification of the Au nanoparticles and the morphology of the Mn3O4 substrate have a joint effect that is responsible for a significant enhancement in the catalytic activity of the Au/Mn3O4 system.
Reduced Carbon Dots versus Oxidized Carbon Dots: Photo‐ and Electrochemiluminescence Investigations for Selected Applications
Authors: Xu Yang , Wu Ming , Feng Xi‐Zeng , Yin Xue‐Bo , He Xi‐Wen , Zhang Yu‐Kui
Published: March 2013

The study of the composition, morphology, and surface structure of carbon dots (Cdots) is critical to understanding their effect on the photo‐ and electrochemiluminescence (PL and ECL) of Cdots in selected applications. Herein, two kinds of Cdots were prepared with 3‐(3,4‐dihydroxyphenyl)‐L‐alanine (L‐DOPA) as precursor. The Cdots prepared by using a carbonization‐extraction strategy have a low oxidation level and are denoted as reduced Cdots (r‐Cdots). The Cdots obtained with a carbonization‐oxidation process are highly oxidized and are denoted as oxidized Cdots (o‐Cdots). The o‐Cdots have a carbon core and oxygen‐containing loose shell, but the r‐Cdots consist mainly of the carbon core. Whereas r‐Cdots have a strong blue PL but no apparent ECL response, o‐Cdots exhibit a relatively weak PL and strong ECL emission. These properties allow for selected applications of the Cdots. The r‐Cdots were used in cell imaging with their high PL emission. The o‐Cdots, with their high ECL efficiencies, were selected to sense Cu2+ with Cu2+‐inducing ECL quenching in the o‐Cdots/K2S2O8 system. This work provides the possibility to control the composition of Cdots for selected applications and shows a good way to characterize surface traps of Cdots because ECL is characterized by the surface‐state and PL is mainly related to the core‐state in Cdots.
Illicium Sesquiterpenes: Divergent Synthetic Strategy and Neurotrophic Activity Studies
Authors: Trzoss Lynnie , Xu Jing , Lacoske Michelle H. , Mobley William C. , Theodorakis Emmanuel A.
Published: March 2013

Majucin‐type sesquiterpenes from Illicium sp., such as jiadifenolide (2), jiadifenin (3), and (1R,10S)‐2‐oxo‐3,4‐dehydroxyneomajucin (4, ODNM), possess a complex caged chemical architecture and remarkable neurotrophic activities. As such, they represent attractive small‐molecule leads against various neurodegenerative diseases. We present an efficient, enantioselective, and unified synthesis of 2, 3, and 4 and designed analogues that diverge from tetracyclic key intermediate 7. The synthesis of 7 is highlighted by the use of an enantioselective Robinson annulation reaction (construction of the AB rings), a Pd‐mediated carbomethoxylation reaction (construction of the C ring), and a one‐pot oxidative reaction cascade (construction of the D ring). Evaluation of the neurotrophic activity of these compounds led to the identification of several highly potent small molecules that significantly enhanced the activity of nerve growth factor (NGF) in PC‐12 cells. Moreover, efforts to define the common pharmacophoric motif suggest that substitution at the C‐10 center significantly affects bioactivity, while the hemiketal moiety of 2 and 3 and the C‐1 substitution might not be critical to the neurotrophic activity.
The prognostic and predictive value of KRAS oncogene substitutions in lung adenocarcinoma
Authors: Villaruz Liza C. , Socinski Mark A. , Cunningham Diana E. , Chiosea Simion I. , Burns Timothy F. , Siegfried Jill M. , Dacic Sanja
Published: March 2013

BACKGROUND

The prognostic and therapeutic implications of the spectrum of v‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) oncogene substitutions in lung cancer remain poorly understood. The objective of this study was to determine whether KRAS oncogene substitutions differed with regard to prognosis or predictive value in lung adenocarcinoma.

METHODS

KRAS oncogene substitutions and mutant allele‐specific imbalance (MASI) were determined in patients with lung adenocarcinoma, and the associations with overall survival (OS), recurrence‐free survival (RFS), and chemotherapy interactions were assessed.

RESULTS

KRAS mutational analysis was performed on 988 lung adenocarcinomas, and 318 KRAS mutations were identified. In this predominantly early stage cohort (78.6% of patients had stage I‐III disease), OS and RFS did not differ according to the type of KRAS substitution (OS, P = .612; RFS, P = .089). There was a trend toward better OS in the subset of patients with KRAS codon 13 mutations (P = .052), but that trend was not significant in multivariate analysis (P = .076). RFS did not differ according to codon type in univariate analysis (P = .322). There was a marked difference in RFS based on the presence of MASI in univariate analysis (P = .004) and multivariate analysis (P = .009). A test for interaction was performed to determine whether the effect of chemotherapy on OS and RFS differed based on KRAS substitution type, codon type, or the presence of MASI. That test indicated that there were no differences in the effects of chemotherapy for any of variables examined.

CONCLUSIONS

KRAS codon 13 mutations and MASI were identified as candidate biomarkers for prognosis, and it may be useful to incorporate them into prospective studies evaluating novel therapies in KRAS‐mutant lung adenocarcinoma. Cancer 2013;119:2268–2274. © 2013 American Cancer Society.
Global and local parametric diagnosis of analog short‐channel CMOS circuits using homotopy‐simplicial algorithm
Authors: Tadeusiewicz Michał , Hałgas Stanisław
Published: March 2013

The paper offers an algorithm for local and global parametric diagnosis in nonlinear analog circuits, including both identification of the faulty parameters and determination their values. The algorithm exploits a nonlinear algebraic type test equations which may possess multiple solutions, corresponding to different sets of the parameters values which meet the test. To find the solutions, the homotopy concept is applied. Since the test equation is not given in explicit analytical form, the simplicial method is used to trace the homotopy path. The proposed approach can be applied to a broad class of analog circuits, including the complementary metal–oxide–semiconductor circuits fabricated in nanometer technology. The developed diagnostic procedure has been implemented in DELPHI, whereas the required by the algorithm repeated circuit analyses are carried out using IsSPICE 4 and both environments have been joined together. For illustration, two numerical examples are given. Copyright © 2013 John Wiley & Sons, Ltd.