bluuebunny/crossref_metadata_2025 huggingface dataset:
A simple and sensitive resonance Rayleigh scattering method for determination of As(III) using aptamer‐modified nanogold as a probe
Authors: Tang Meiling , Wen Guiqing , Liang Aihui , Jiang Zhiliang
Published: October 2013

A simple and selective aptamer (ssDNA)‐modified nanogold probe (AussDNA) was prepared for the determination of trace As(III) in HEPES buffer solution (pH 8.2) containing 0.05 mol/L NaCl. The method coupled the aptamer reaction of AussDNA–As(III) and the resonance Rayleigh scattering (RRS) of nanogold aggregations at 278 nm. When the As(III) concentration increased, the RRS intensity at 278 nm increased to form more nanogold aggregation and a stable As(III)–ssDNA complex. Under selected conditions, the increased RRS intensity (ΔI) was linear to the concentration of As(III) in the range 3.8–230.4 ng/mL, with a detection limit of 1.9 ng/mL. This RRS method was applied to detect As(III) in water samples, with simplicity, sensitivity and selectivity. Copyright © 2013 John Wiley & Sons, Ltd.
A DAF‐16/FoxO3a‐dependent longevity signal is initiated by antioxidants
Authors: Kim Juewon , Ishihara Naoko , Lee Tae Ryong
Published: October 2013

The precise mechanisms of antioxidant‐mediated longevity are poorly understood. We show that an antioxidant treatment can extend the lifespan of Caenorhabditis elegans (C. elegans) through the nuclear translocation of the forkhead box O transcription factor (FoxO) homolog DAF‐16. This pathway was found to involve 3‐phosphoinositide‐dependent kinase‐1 (PDK‐1) and serum‐ and glucocorticoid‐regulated kinase‐1 (SGK‐1), distinct from the known oxidative stress‐mediated mechanism in which FoxO3a translocation is regulated by c‐Jun N‐terminal kinase (JNK) and mammalian sterile 20‐like kinase‐1 (MST‐1). The differences in the mechanisms of FoxO activation by antioxidants and oxidants result in differences in FoxO phosphorylation and target gene expression. Based on these results, we found that a combination of early antioxidant treatment and late oxidant treatment is most effective for lifespan extension in C. elegans. © 2013 BioFactors, 40(2):247–257, 2014
Thermal denaturation and aggregation of apoform of glycogen phosphorylase b. Effect of crowding agents and chaperones
Authors: Eronina Tatyana B. , Chebotareva Natalia A. , Roman Svetlana G. , Kleymenov Sergey Yu. , Makeeva Valentina F. , Poliansky Nikolay B. , Muranov Konstantin O. , Kurganov Boris I.
Published: October 2013

The effect of protein and chemical chaperones and crowders on thermal stability and aggregation of apoform of rabbit muscle glycogen phosphorylase b (apoPhb) has been studied at 37°C. Proline suppressed heat‐induced loss in ability of apoPhb to reconstitution at 37°C, whereas α‐crystallin did not reveal a protective action. To compare the antiaggregation activity of intact and crosslinked α‐crystallins, an adsorption capacity (AC) of a protein chaperone with respect to a target protein was estimated. This parameter is a measure of the antiaggregation activity. Crosslinking of α‐crystallin results in 11‐fold decrease in the initial AC. The nonlinear character of the relative initial rate of apoPhb aggregation versus the [intact α‐crystallin]/[apoPhb] ratio plot is indicative of the decrease in the AC of α‐crystallin with increasing the [α‐crystallin]/[apoPhb] ratio and can be interpreted as an evidence for dynamic chaperone structure and polydispersity of α‐crystallin–target protein complexes. As for chemical chaperones, a semisaturation concentration of the latter was used as a characteristic of the antiaggregation activity. A decrease in the semisaturation concentration for proline was observed in the presence of the crowders (polyethylene glycol and Ficoll‐70). © 2013 Wiley Periodicals, Inc. Biopolymers 101: 504–516, 2014.
Central metabolic responses to the overproduction of fatty acids in Escherichia coli based on 13C‐metabolic flux analysis
Authors: He Lian , Xiao Yi , Gebreselassie Nikodimos , Zhang Fuzhong , Antoniewicz Maciek R. , Tang Yinjie J. , Peng Lifeng
Published: October 2013

We engineered a fatty acid overproducing Escherichia coli strain through overexpressing tesA (“pull”) and fadR (“push”) and knocking out fadE (“block”). This “pull‐push‐block” strategy yielded 0.17 g of fatty acids (C12–C18) per gram of glucose (equivalent to 48% of the maximum theoretical yield) in batch cultures during the exponential growth phase under aerobic conditions. Metabolic fluxes were determined for the engineered E. coli and its control strain using tracer ([1,2‐13C]glucose) experiments and 13C‐metabolic flux analysis. Cofactor (NADPH) and energy (ATP) balances were also investigated for both strains based on estimated fluxes. Compared to the control strain, fatty acid overproduction led to significant metabolic responses in the central metabolism: (1) Acetic acid secretion flux decreased 10‐fold; (2) Pentose phosphate pathway and Entner–Doudoroff pathway fluxes increased 1.5‐ and 2.0‐fold, respectively; (3) Biomass synthesis flux was reduced 1.9‐fold; (4) Anaplerotic phosphoenolpyruvate carboxylation flux decreased 1.7‐fold; (5) Transhydrogenation flux converting NADH to NADPH increased by 1.7‐fold. Real‐time quantitative RT‐PCR analysis revealed the engineered strain increased the transcription levels of pntA (encoding the membrane‐bound transhydrogenase) by 2.1‐fold and udhA (encoding the soluble transhydrogenase) by 1.4‐fold, which is in agreement with the increased transhydrogenation flux. Cofactor and energy balances analyses showed that the fatty acid overproducing E. coli consumed significantly higher cellular maintenance energy than the control strain. We discussed the strategies to future strain development and process improvements for fatty acid production in E. coli. Biotechnol. Bioeng. 2014;111: 575–585. © 2013 Wiley Periodicals, Inc.
Aggregates of α‐chymotrypsinogen anneal to access more stable states
Authors: Maurer Ronald W. , Hunter Alan K. , Robinson Anne S. , Roberts Christopher J.
Published: October 2013

Non‐native protein aggregates present a variety of problems in fundamental and applied biochemistry and biotechnology, from quality and safety issues in pharmaceutical development to their association with a number of chronic diseases. The aggregated, often amyloid, protein state is often considered to be more thermodynamically and kinetically stable than (partially) unfolded or folded monomers except under highly denaturing conditions. However, evolution of the structure and stability of aggregated states has received much less attention. Here it is shown that under mildly‐denaturing conditions (elevated temperature or [urea]), where the native monomer (N) is slightly favored compared to the unfolded state (U), α‐chymotrypsinogen A (aCgn) non‐native aggregates undergo a structural relaxation or annealing process to reach even more stable states. The annealed aggregates are more resistant to dissociation than aggregates that do not undergo this relaxation process. Aggregates without annealing dissociate via linear chain depolymerization, and annealing is accelerated under conditions that promote slow dissociation (partially denaturing conditions). This is consistent with a free energy landscape with multiple barriers and local minima that allows for a kinetic competition between aggregate dissociation and structural relaxation to more stable aggregate states. This highlights added complexities for protein refolding or aggregate dissociation processes, and may explain why it is often difficult to completely recover monomeric protein from aggregates. Biotechnol. Biotechnol. Bioeng. 2014;111: 782–791. © 2013 Wiley Periodicals, Inc.
Deceleration‐stats save much time during phototrophic culture optimization
Authors: Hoekema Sebastiaan , Rinzema Arjen , Tramper Johannes , Wijffels René H. , Janssen Marcel
Published: October 2013

In case of phototrophic cultures, photobioreactor costs contribute significantly to the total operating costs. Therefore one of the most important parameters to be determined is the maximum biomass production rate, if biomass or a biomass associated product is the desired product. This is traditionally determined in time consuming series of chemostat cultivations. The goal of this work is to assess the experimental time that can be saved by applying the deceleration stat (D‐stat) technique to assess the maximum biomass production rate of a phototrophic cultivation system, instead of a series of chemostat cultures. A mathematical model developed by Geider and co‐workers was adapted in order to describe the rate of photosynthesis as a function of the local light intensity. This is essential for the accurate description of biomass productivity in phototrophic cultures. The presented simulations demonstrate that D‐stat experiments executed in the absence of pseudo steady‐state (i.e., the arbitrary situation that the observed specific growth rate deviates <5% from the dilution rate) can still be used to accurately determine the maximum biomass productivity of the system. Moreover, this approach saves up to 94% of the time required to perform a series of chemostat experiments that has the same accuracy. In case more information on the properties of the system is required, the reduction in experimental time is reduced but still significant. Biotechnol. Bioeng. 2014;111: 792–802. © 2013 Wiley Periodicals, Inc.
A quantitative analysis of the polyamine in lung cancer patient fingernails by LC‐ESI‐MS/MS
Authors: Min Jun Zhe , Matsumoto Akihito , Li Gao , Jiang Ying‐Zi , Yu Hai‐fu , Todoroki Kenichiro , Inoue Koichi , Toyo'oka Toshimasa
Published: October 2013

A quantitative analysis of polyamines in lung cancer patient fingernails by the combination of 4‐(N,N‐dimethylaminosulfonyl)‐7‐fluoro‐2,1,3‐benzoxadiazole derivatives and liquid chromatography–electrospray ionization tandem mass spectrometry is described. The reaction of the reagent with eight kinds of polyamines, that is, N1‐acetylputrescine (N1‐actPUT), N8‐acetylspermidine, N1‐acetylspermine, 1,3‐diaminopropane, putrescine (PUT), cadaverine, spermidine and spermine (SPM) effectively occurs at 60 °C for 30 min. The detection limits (signal‐to‐noise ratio 5) were 5–100 fmol. A good linearity was achieved from the calibration curves, which was obtained by plotting the peak area ratios of the analytes relative to the internal standard (IS), that is, 1,6‐diaminohexane, vs the injected amounts of polyamines (r2 > 0.996), and the intra‐day and inter‐day assay precisions were <9.84%. Furthermore, the recoveries (%) of the polyamines spiked in the human fingernails were 89.14–110.64. The present method was applied to human fingernail samples from 17 lung cancer patients and 39 healthy volunteers. The polyamine concentration was different based on the gender, that is, the N1‐actPUT and PUT contents were 3.10 times and 2.56 times higher in healthy men than in women, respectively. Additionally, in the lung cancer patient group, as compared with the healthy volunteers, the concentrations of SPM had a statistically significant (p < 0.05) correlation. Therefore, because the proposed method provides a good mass accuracy and the trace detection of the polyamines in human fingernails, this analytical technique could be a noninvasive technique to assist in the diagnosis and assessment of disease activity in lung cancer patients. Copyright © 2013 John Wiley & Sons, Ltd.
Comparison of diabetes patients with “demyelinating” diabetic sensorimotor polyneuropathy to those diagnosed with CIDP
Authors: Dunnigan Samantha K. , Ebadi Hamid , Breiner Ari , Katzberg Hans D. , Lovblom Leif E. , Perkins Bruce A. , Bril Vera
Published: October 2013

Background

We have previously identified a subset of diabetic sensorimotor polyneuropathy (DSP) patients with probable demyelination related to poor glycemic control. We aimed to determine whether the clinical characteristics and electrodiagnostic classification of nerve injury in diabetes patients with “demyelinating” DSP (D‐DSP) differed from those diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) (CIDP + diabetes mellitus [DM]).

Methods

D‐DSP (56) and CIDP + DM (67) subjects underwent clinical examination and nerve conduction studies (NCS), and were compared using analysis of variance, contingency tables, and Kruskal–Wallis analyses.

Results

Of the 123 subjects with a mean age of 60.5 ± 15.6 years and mean hemoglobin A1c (HbA1c) of 8.2 ± 2.2%, 54% had CIDP + DM and 46% had D‐DSP. CIDP + DM subjects were older (P = 0.0003), had shorter duration of diabetes (P = 0.005), and more severe neuropathy as indicated by Toronto Clinical Neuropathy Score (TCNS) (P = 0.003), deep tendon reflexes (P = 0.02), and vibration perception thresholds (VPT) (P = 0.01, P = 0.02). The mean HbA1c value for D‐DSP subjects (8.9 ± 2.3%) was higher than in CIDP + DM subjects (7.7 ± 2.0%, P = 0.02).

Conclusions

The clinical phenotype and electrophysiological profile of CIDP + DM patients is marked by more severe neuropathy and better glycemic control than in patients with D‐DSP. These findings indicate that these two conditions – despite similarities in their electrophysiological pattern of demyelination – likely differ in etiology.
Do Greenhouse Gas Emissions Affect Financial Performance? – an Empirical Examination of Australian Public Firms
Authors: Wang Lei , Li Steven , Gao Simon
Published: October 2013

Previous studies that have attempted to relate corporate environmental performance to financial performance have generated conflicting results. This paper presents the findings of a study on the relationship between greenhouse gas (GHG) emissions and the financial performance of Australian corporations. Using multiple regression models and data from a sample of 69 Australian public companies, this paper finds a positive correlation between GHG emissions and corporate financial performance. By testing the statistical significance of GHG emission factors in determining company Tobin's q, this study finds that a stronger Tobin's q often correlates with higher GHG emissions across all industry sectors. This finding is contrary to evidence found in previous studies conducted in other countries. The positive correlation found in this study could be explained with reference to the unique economic structure and development of Australia, particularly its dominant mining industry. Copyright © 2013 John Wiley & Sons, Ltd and ERP Environment
The Neuroethics and Neurolaw of Brain Injury
Authors: Aggarwal Neil Krishan , Ford Elizabeth
Published: October 2013

Neuroethics and neurolaw are fields of study that involve the interface of neuroscience with clinical and legal decision‐making. The past two decades have seen increasing attention being paid to both fields, in large part because of the advances in neuroimaging techniques and improved ability to visualize and measure brain structure and function. Traumatic brain injury (TBI), along with its acute and chronic sequelae, has emerged as a focus of neuroethical issues, such as informed consent for treatment and research, diagnostic and prognostic uncertainties, and the subjectivity of interpretation of data. The law has also more frequently considered TBI in criminal settings for exculpation, mitigation and sentencing purposes and in tort and administrative law for personal injury, disability and worker's compensation cases. This article provides an overview of these topics with an emphasis on the current challenges that the neuroscience of TBI faces in the medicolegal arena. Copyright © 2013 John Wiley & Sons, Ltd.
Can Serial Rapists be Distinguished from One‐off Rapists?
Authors: Slater Chelsea , Woodhams Jessica , Hamilton‐Giachritsis Catherine
Published: October 2013

There are investigative advantages to being able to determine early in a police investigation whether a rape has been committed by a serial or a one‐off rapist. Previous research has found some differences in the crime‐scene behaviors of serial and one‐off rapists; however, this research suffers from the limitation of utilizing a sample of rapes within which there was a mixture of victim–offender relationships. To address this limitation, this study sampled 38 serial (two or more convictions) and 50 one‐off (one conviction)strangerrapists and compared their crime scene behavior across four domains (control, sex, escape and style behaviors). Serial and one‐off rapists differed in some control and sexual behaviors, in particular, in the type of victim targeted, the offense locations, methods of control and the sexual acts forced upon the victim. However, the results did not indicate a striking difference in the offending behavior of the two groups. The implications of these findings for criminal investigations are discussed. Copyright © 2013 John Wiley & Sons, Ltd.
Customization of copolymers to optimize selectivity and yield in polymer‐driven antibody purification processes
Authors: Capito Florian , Skudas Romas , Stanislawski Bernd , Kolmar Harald
Published: October 2013

This manuscript describes customization of copolymers to be used for polymer‐driven protein purification in bioprocessing. To understand how copolymer customization can be used for fine‐tuning, precipitation behavior was analyzed for five target antibodies (mAbs) and BSA as model impurity protein, at ionic strength similar to undiluted cell culture fluid. In contrast to the use of standardized homopolymers, customized copolymers, composed of 2‐acrylamido‐2‐methylpropane sulfonic acid (AMPS) and 4‐(acryloylamino)benzoic acid (ABZ), exhibited antibody precipitation yields exceeding 90%. Additionally, copolymer average molecular weight (Mw) was varied and its influence on precipitation yield and contaminant coprecipitation was investigated. Results revealed copolymer composition as the major driving force for precipitation selectivity, which was also dependent on protein hydrophobicity. By adjusting ABZ content and Mw of the precipitant for each of the mAbs, conditions were found that allowed for high precipitation yield and selectivity. These findings may open up new avenues for using polymers in antibody purification processes. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:1484–1493, 2013
Continuous cultivation of human hamstring tenocytes on microcarriers in a spinner flask bioreactor system
Authors: Stich Stefan , Ibold Yvonne , Abbas Amro , Ullah Mujib , Sittinger Michael , Ringe Jochen , Schulze‐Tanzil Gundula , Müller Christiane , Kohl Benjamin , John Thilo
Published: October 2013

Tendon healing is a time consuming process leading to the formation of a functionally altered reparative tissue. Tissue engineering‐based tendon reconstruction is attracting more and more interest. The aim of this study was to establish tenocyte expansion on microcarriers in continuous bioreactor cultures and to study tenocyte behavior during this new approach. Human hamstring tendon‐derived tenocytes were expanded in monolayer culture before being seeded at two different seeding densities (2.00 and 4.00 × 106 cells/1000 cm2 surface) on Cytodex™ type 3 microcarriers. Tenocytes' vitality, growth kinetics and glucose/lactic acid metabolism were determined dependent on the seeding densities and stirring velocities (20 or 40 rpm) in a spinner flask bioreactor over a period of 2 weeks. Gene expression profiles of tendon extracellular matrix (ECM) markers (type I/III collagen, decorin, cartilage oligomeric protein [COMP], aggrecan) and the tendon marker scleraxis were analyzed using real time detection polymerase chain reaction (RTD‐PCR). Type I collagen and decorin deposition was demonstrated applying immunolabeling. Tenocytes adhered on the carriers, remained vital, proliferated and revealed an increasing glucose consumption and lactic acid formation under all culture conditions. “Bead‐to‐bead” transfer of cells from one microcarrier to another, a prerequisite for continuous tenocyte expansion, was demonstrated by scanning electron microscopy. Type I and type III collagen gene expression was mainly unaffected, whereas aggrecan and partly also decorin and COMP expression was significantly downregulated compared to monolayer cultures. Scleraxis gene expression revealed no significant regulation on the carriers. In conclusion, tenocytes could be successfully expanded on microcarriers. Therefore, bioreactors are promising tools for continuous tenocyte expansion. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 30:142–151, 2014
The stimulatory effect of mannitol on levan biosynthesis: Lessons from metabolic systems analysis of Halomonas smyrnensis AAD6T
Authors: Ates Ozlem , Arga Kazim Y. , Oner Ebru Toksoy
Published: October 2013

Halomonas smyrnensis AADT is a halophilic, gram‐negative bacterium that can efficiently produce levan from sucrose as carbon source via levansucrase activity. However, systems‐based approaches are required to further enhance its metabolic performance for industrial application. As an important step toward this goal, the genome‐scale metabolic network of Chromohalobacter salexigens DSM3043, which is considered a model organism for halophilic bacteria, has been reconstructed based on its genome annotation, physiological information, and biochemical information. In the present work, the genome‐scale metabolic network of C. salexigens was recruited, and refined via integration of the available biochemical, physiological, and phenotypic features of H. smyrnensis AAD6T. The generic metabolic model, which comprises 1,393 metabolites and 1,108 reactions, was then systematically analyzed in silico using constraints‐based simulations. To elucidate the relationship between levan biosynthesis and other metabolic processes, an enzyme‐graph representation of the metabolic network and a graph decomposition technique were employed. Using the concept of control effective fluxes, significant links between several metabolic processes and levan biosynthesis were estimated. The major finding was the elucidation of the stimulatory effect of mannitol on levan biosynthesis, which was further verified experimentally via supplementation of mannitol to the fermentation medium. The optimal concentration of 30 g/L mannitol supplemented to the 50 g/L sucrose‐based medium resulted in a twofold increase in levan production in parallel with increased sucrose hydrolysis rate, accumulated extracellular glucose, and decreased fructose uptake rate. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:1386–1397, 2013
The effects of membrane filters used in biopharmaceutical processes on the concentration and composition of polysorbate 20
Authors: Lei Ming , Hewitt Daniel , Cornell Christopher , Skidmore Ken , Kao Yung‐Hsiang , Sugahara Jimmy , Beane Diane , Ji Junyan
Published: October 2013

Polysorbate 20 (PS‐20) is often included in the formulation for therapeutic proteins to reduce protein aggregation and surface adsorption. During the production process of therapeutic proteins, various membrane filters are used to filter product pools containing PS‐20. The purpose of this study is to quantify the effects of these membrane filtration processes on the concentration and composition of PS‐20. A quantitative understanding of this process provides the knowledge base for better controlling the consistency of formulation excipients in drug products. PS‐20 solutions (without protein) were filtered through either 0.2 µm sterilizing filters or membrane filters with 30 kDa MWCO. The concentration of PS‐20 was measured by a mixed‐mode chromatography method and a nuclear magnetic resonance spectroscopy (NMR) assay. The composition of PS‐20 was characterized by 1H‐NMR and a reverse‐phase chromatography method. Non‐specific adsorption of PS‐20 on both the sterilizing filter and 30 kDa MWCO membrane filter was quantified. Composition of PS‐20 was altered after 30 kDa MWCO membrane filtration, possibly because the different interactions between heterogeneous PS‐20 components and the 30 kDa MWCO membrane were not uniform. As a result, the retentate after the 30 kDa MWCO membrane filtration step contains no POE sorbitan and increased amount of POE sorbitan di‐esters and tri‐esters. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:1503–1511, 2013
An unusual origin of the celiac trunk and the superior mesenteric artery in the thorax
Authors: Matusz Petru , Iacob Nicoleta , Miclaus Gratian D. , Pureca Ana , Ples Horia , Loukas Marios , Tubbs R. Shane
Published: October 2013

The authors report a case of a 44‐year‐old male found to have unusual origins of the celiac trunk (CT) and superior mesernteric artrery (SMA) as revealed by routine multidetector computed tomograph (MDCT) angiography. The CT and SMA originate from the thoracic aorta (TA) 21 mm and 9 mm above the aortic hiatus, respectively. The median arcuate ligament (MAL) is located at the level of the L1–L2 intervertebral disc. The course of the CT descends in the thoracic cavity making a 14° acute downward angle in front of the TA; below the level of the MAL, the CT descends, making an angle of 47°. The course of the SMA descends at both the thoracic and abdominal level making an angle of 17°, and having an aortomesenteric distance of 9 mm at the level of the third part of the duodenum. In the present case, the supradiaphragmatic origin of the CT and the SMA was determined by their incomplete caudal descent, associated with a pronounced apparent descent of the diaphragm. A thoracic origin of the CT and SMA and the acute downward aortomesenteric angle (17°) associated with a reduced aortomesenteric distance at the level of the third part of the duodenum (9 mm), although no clinical signs are present, may predispose the patient to develop simultaneously a triple syndrome: the compression of CT by MAL (celiac axis compression syndrome), the compression of SMA by MAL (superior mesenteric artery compression syndrome), and the compression of the duodenum by the SMA (superior mesenteric artery syndrome). Clin. Anat. 26:975–979, 2013. © 2013 Wiley Periodicals, Inc.
Oncologists’ attitudes toward KRAS testing: a multisite study
Authors: Harris Julie N. , Liljestrand Petra , Alexander Gwen L. , Goddard Katrina A. B. , Kauffman Tia , Kolevska Tatjana , McCarty Catherine , O'Neill Suzanne , Pawloski Pamala , Rahm Alanna , Williams Andrew , Somkin Carol P.
Published: October 2013

Recent discoveries promise increasingly to help oncologists individually tailor anticancer therapy to their patients’ molecular tumor characteristics. One such promising molecular diagnostic is Kirsten ras (KRAS) tumor mutation testing for metastatic colorectal cancer (mCRC) patients. In the current study, we examined how and why physicians adopt KRAS testing and how they subsequently utilize the information when discussing treatment strategies with patients. We conducted 34 semi‐structured in‐person or telephone interviews with oncologists from seven different health plans. Each interview was audiotaped, transcribed, and coded using qualitative research methods. Information and salient themes relating to the research questions were summarized for each interview. All of the oncologists in this study reported using the KRAS test at the time of the interview. Most appeared to have adopted the test rapidly, within 6 months of the publication of National Clinical Guidelines. Oncologists chose to administer the test at various time points, although the majority ordered the test at the time their patient was diagnosed with mCRC. While oncologists expressed a range of opinions about the KRAS test, there was a general consensus that the test was useful and provided benefits to mCRC patients. The rapid adoption and enthusiasm for KRAS suggests that these types of tests may be filling an important informational need for oncologists when making treatment decisions. Future research should focus on the informational needs of patients around this test and whether patients feel informed or confident with their physicians’ use of these tests to determine treatment access.
Small endometrial carcinoma 10 mm or less in diameter: clinicopathologic and histogenetic study of 131 cases for early detection and treatment
Authors: Hasumi Katsuhiko , Sugiyama Yuko , Sakamoto Kimihiko , Akiyama Futoshi
Published: October 2013

Natural history and clinicopathologic features of early endometrial carcinoma are not evident. Its knowledge is essential to make up strategies for prevention, early detection, and treatment of endometrial carcinoma. Especially it is important to know pathways of endometrial carcinogenesis and frequency of endometrial carcinomas arising from endometrial hyperplasia. Clinicopathologically 131 patients with endometrial carcinoma measuring ≤10 mm in diameter (“small endometrial carcinoma”) were studied to get useful information for early diagnosis, treatment, and histogenesis. The entire endometrium of surgically removed uterus was step‐cut and examined. The patients were, on average, 5 years younger than the controls whose carcinomas measure >10 mm (P < 0.0001). Of the 131 patients, 20% were asymptomatic although only 5% of the controls were asymptomatic (P < 0.0001). Seventy‐six percent had the carcinomas located in the upper third section of the uterine corpus. Macroscopically 44% of the tumors were flat and 56% were elevated. Incidence of nodal and ovarian metastases were <1%. Forty percent of “small endometrial carcinomas” were associated with endometrial hyperplasia and 60% were not. It is logical to believe that there are two pathways of endometrial carcinogenesis: carcinomas occurring from hyperplasia (40%) and carcinomas occurring from normal endometrium (60%). As hyperplasia‐carcinoma sequence is not a main route, we cannot probably prevent carcinomas only by treatment of hyperplasia. Effort must be focused on detecting early de novo carcinomas. As most “small endometrial carcinomas” arise in the upper third of the corpus, careful endometrial sampling there is important for early detection.
Prognostic value of CtIP/RBBP8 expression in breast cancer
Authors: Soria‐Bretones Isabel , Sáez Carmen , Ruíz‐Borrego Manuel , Japón Miguel A. , Huertas Pablo
Published: October 2013

CtIP/RBBP8 is a multifunctional protein involved in transcription, DNA replication, DNA repair by homologous recombination and the G1 and G2 checkpoints. Its multiple roles are controlled by its interaction with several specific factors, including the tumor suppressor proteins BRCA1 and retinoblastoma. Both its functions and interactors point to a putative oncogenic potential of CtIP/RBBP8 loss. However, CtIP/RBBP8 relevance in breast tumor appearance, development, and prognosis has yet to be established. We performed a retrospective analysis of CtIP/RBBP8 and RB1 levels by immunohistochemistry using 384 paraffin‐embedded breast cancer biopsies obtained during tumor removal surgery. We have observed that low or no expression of CtIP/RBBP8 correlates with high‐grade breast cancer and with nodal metastasis. Reduction on CtIP/RBBP8 is most common in hormone receptor (HR)‐negative, HER2‐positive, and basal‐like tumors. We observed lower levels of RB1 on those tumors with reduced CtIP/RBBP8 levels. On luminal tumors, decreased but not absence of CtIP/RBBP8 levels correlate with increased disease‐free survival when treated with a combination of hormone, radio, and chemo therapies.
Clinical and demographic characteristics associated with the receipt of chemotherapy treatment among 7951 elderly metastatic colon cancer patients
Authors: Reese Emily S. , Onukwugha Eberechukwu , Hanna Nader , Seal Brian S. , Mullins C. Daniel
Published: October 2013

Among older individuals diagnosed with metastatic colon cancer (mCC) there is limited evidence available that describes the characteristics associated with advancing to second‐ and subsequent lines of treatment with chemotherapy/biologics. Our objective was to describe the trends and lines of treatment received among elderly mCC patients. Elderly beneficiaries diagnosed with mCC from 2003 to 2007 were identified in the Surveillance, Epidemiology and End Results (SEER)‐Medicare dataset. Beneficiaries were followed up until death or censoring. Treatment lines were classified in combinations of chemotherapies and biologics. Modified Poisson regression was used to predict receipt of lines of treatment. Analyses controlled for age, race/ethnicity, gender, marital status, state buy‐in during diagnosis year, SEER‐registry site, Charlson comorbidity index (CCI), poor performance indicators, surgery of primary site, and surgery of regional/distal sites. Among 7951 Medicare beneficiaries identified with mCC, 3266 initiated therapy. Of these, 1440 advanced to second‐line treatment. Of these, 274 advanced to a subsequent‐line treatment. Surgeries of the primary tumor site and of the regional/distal sites and marital status were the most significant variables associated with advancing through second‐ and subsequent‐line treatments. Greater than 80 years of age, African American race, SEER‐registry area, less than 6 months state buy‐in assistance in mCC diagnosis year, and having poor performance indicators were inversely associated with receipt of second‐ or subsequent‐line treatments. Among elderly individuals diagnosed with mCC, we identified demographic, clinical, and regional factors associated with receipt of second‐ and subsequent‐line chemotherapy/biologics. Additional research is warranted to understand the role of physician versus patient preferences as well as geographic differences explaining why patients advance through lines of chemotherapy.
Risk and Protective Factors for Physical and Emotional Abuse Victimisation amongst Vulnerable Children in South Africa
Authors: Meinck Franziska , Cluver Lucie D. , Boyes Mark E. , Ndhlovu Lodrick D.
Published: October 2013

Little is known about risk and protective factors for emotional and physical child abuse in South Africa. Existing research has focused largely on sexual abuse and relied on recollections of childhood abuse from university and high‐school students or data from criminal reports. The objective of this study was to establish risk and protective factors for severe physical and emotional abuse amongst a large cross‐sectional community sample of South African youth. Confidential self‐report questionnaires were completed by children aged 13–19 (n = 603, 47.9% female) with local interviewers in deprived areas of South Africa. Standardised measures of abuse, hypothesised risk factors and socio‐demographic variables were used. Factors associated with severe physical and emotional child abuse were experience of family conflict (p = 0.003), unequal food distribution (p < 0.014), inconsistent discipline (p = 0.012), number of caregiver changes (p = 0.022), living with a step‐parent (p = 0.034), caregiver disability (p = 0.004), food insecurity (p = 0.006), bullying (p < 0.001), acquired immunodeficiency syndrome (AIDS)‐related stigma (p < 0.001), sexual abuse (p = 0.003), school non‐attendance (p = 0.006) and non‐achievement (p = 0.015). These identified risk and protective factors at community, school, caregiver and household levels have the potential to affect the risk of abuse for children in South Africa, and may be valuable fields for future intervention efforts. Copyright © 2013 John Wiley & Sons, Ltd.

‘The objective of this study was to establish risk and protective factors for severe physical and emotional abuse amongst a large cross‐sectional sample of South African youth’

Key Practitioner Messages

Risk and protective factors for physical and emotional child abuse have not been thoroughly studied in South Africa.

Risk and protective factors for child abuse in South Africa include poverty, AIDS‐related stigma, bullying, school non‐attendance and achievement, sexual abuse, caregiver disability, inconsistent discipline, family conflict and living with a step‐parent.

Future research should focus on longitudinal data to establish causality and to examine the relationship between child abuse and caregiver AIDS sickness.
Young People's Experiences of Going Missing From Care: A Qualitative Investigation using Peer Researchers
Authors: Taylor Julie , Bradbury‐Jones Caroline , Hunter Helen , Sanford Kate , Rahilly Tom , Ibrahim Nayla
Published: October 2013

Looked after children are significantly more likely than other children to go missing. They face significant risk of harm through, for example, exposure to alcohol, drugs and sexual victimisation. While research identifies some factors which may reduce the likelihood of looked after children going missing, it is recognised that a greater understanding of effective practice is needed. The aim of the study was to investigate young people's experiences of going missing from care and to identify the issues that contributed to them running away; trigger factors that prompted episodes of going missing; support received during or following instances where they went missing; and factors that might prevent future absconding. Research on children's experiences is often reported from the adult's perspective rather than allowing children to have a voice. We therefore recruited two young people to collaborate with the researchers as peer researchers. A qualitative study was undertaken using the Critical Incident Technique. Twenty‐eight young people with a history of running away were recruited from different locations in Scotland. They took part in six focus groups, which were held during May 2012. Data were analysed using a framework approach. Four themes were identified regarding reasons for running away: authority and power; friction; isolation; and environmental issues. Commonly cited consequences were being ‘grounded’ and having shoes removed (to prevent further running away). Young people were critical of a lack of support on return and a lack of boundaries. They stressed the importance of being heard, being treated with respect, being able to exercise autonomy and feeling that someone cares. Copyright © 2013 John Wiley & Sons, Ltd.

Key Practitioner Messages

Looked after children are significantly more likely than other children to go missing.

When missing, young people are exposed to significant risk of harm.

Reasons for running away are: authority and power; friction; isolation; and environmental issues.

Approaches to responding to young people who go missing should be supportive and facilitative rather than punitive.

Being heard, being treated with respect, being able to exercise autonomy and feeling that someone cares are crucial preventative factors.

‘Research on children's experiences is often reported from the adult's perspective’

‘Young people were critical of a lack of support on return and a lack of boundaries’
Beyond Skills and Structure: Justice Dispositions as Antecedents of Young Citizens' Volunteering and Political Participation
Authors: Neufeind Max , Jiranek Patrick , Wehner Theo
Published: October 2013

Community involvement is usually attributed to opportunity structures and individuals' ability to be involved. Building on psychological justice research, this paper proposes that justice dispositions add to explaining why young citizens become active in their communities or not. Furthermore, it is argued that justice dispositions help to understand why most studies find only moderate relationships between youth volunteering and forms of political involvement. In a sample of 321 young Swiss volunteers, this study shows justice centrality and belief in a just world to predict the extent of volunteering and political participation, even after controlling for civic skills and opportunity structures. However, scrutinising the motivations to volunteer, self‐oriented motivations (enhancement, social, career and understanding) more strongly affected the level of volunteering than motivations related to justice dispositions (political responsibility and social responsibility). These findings have implications for the attraction and retention of volunteers as well as for the politics of volunteering and community development in general. Copyright © 2013 John Wiley & Sons, Ltd.
Differential gene expression of the key signalling pathway in para‐carcinoma, carcinoma and relapse human pancreatic cancer
Authors: Chang Zheng‐Yan , Sun Ran , Ma Yu‐Shui , Fu Da , Lai Xiao‐Long , Li Yu‐Sheng , Wang Xing‐Hong , Zhang Xiao‐Ping , Lv Zhong‐Wei , Cong Xian‐Ling , Li Wen‐Ping
Published: October 2013

Pancreatic cancer (PC) has a high rate of mortality and a poorly understood mechanism of progression. Investigation of the molecular mechanism of PC and exploration of the specific markers for early diagnosis and specific targets of therapy are key points to prevent and treat PC effectively and to improve their prognosis. In our study, expression profiles experiment of para‐carcinoma, carcinoma and relapse human PC was performed using Agilent human whole genomic oligonucleotide microarrays with 45 000 probes. Differentially expressed genes related with PC were screened and analysed further by Gene Ontology term analysis and Kyoto encyclopaedia of genes and genomes pathway analysis. Our results showed that there were 3853 differentially expressed genes associated with pancreatic carcinogenesis and relapse. In addition, our study found that PC was related to the Jak–STAT signalling pathway, PPAR signalling pathway and Calcium signalling pathway, indicating their potential roles in pancreatic carcinogenesis and progress. Copyright © 2013 John Wiley & Sons, Ltd.
Small‐Molecule Mechanism of Action Studies in Caenorhabditis elegans
Authors: Zlotkowski Katherine , Eliasen Anders M. , Mitra Aurpon , Siegel Dionicio
Published: October 2013

A general protocol for exogenous small‐molecule pull‐down experiments with Caenorhabditis elegans is described; it provides a link between small‐molecule screens in worms and existing mutant and RNAi technologies, thereby enabling organismal mechanism of action studies for the natural product clovanemagnolol. Forward chemical genetic screens followed by mechanism of action studies with C. elegans, when coupled with genetic validation of identified targets to reproduce the small molecule's phenotypic effects, provide a unique platform for discovering the biological targets of compounds that affect multicellular processes. First, the use of an immobilized FK506 derivative and soluble competition experiments with optimally prepared soluble C. elegans proteome successfully identified interactions with FK506 binding proteins 1 to 6. This approach was used to determine an unknown mechanism of action for clovanemagnolol, a small molecule that promotes axonal branching in both primary neuronal cultures and in vivo in C. elegans. Following the synthesis of an appropriately functionalized solid‐phase reagent bearing a clovanemagnolol analogue pull‐down experiments employing soluble competition identified kinesin light chain‐1 (KLC‐1), a protein involved in axonal cargo transport, as a putative target. This was corroborated through the use of mutant worms lacking klc‐1 and possessing GFP neuronal labeling, reproducing the axonal branching phenotype induced by the small molecule clovanemagnolol.
Cytoplasmic extension peptide of Pichia pastoris glucose sensor Gss1 is not compulsory for glucose signalling
Authors: Polupanov Andriy S. , Sibirny Andriy A.
Published: October 2013

In the methylotrophic yeast, Pichia pastoris, Gss1 protein is a glucose sensor involved in pexophagy, glucose utilization and glucose catabolite repression. This study identifies that deletion of 150 residues of Gss1 affects slightly glucose catabolite repression and pexophagy, while maintaining signalling function of Gss1. Substitution of one conserved amino acid R180K of Gss1 protein has no visible phenotype, in contrast to corresponding changes in glucose sensors from other yeast species. We suggest that C‐terminal cytoplasmic extension of PpGss1plays different role to that of its homologs in Saccharomyces cerevisiae and Hansenula polymorpha.
Successful closure of residual leak following lariat procedure in a patient with high risk of stroke and hemorrhage
Authors: Yeow Wen‐Loong , Matsumoto Takashi , Kar Saibal
Published: October 2013

Percutaneous left atrial appendage suture ligation with the LARIAT® device (Sentre HEART, Redwood City, CA) was successfully performed on an 84‐year‐old woman with non‐valvular atrial fibrillation who developed intracranial hemorrhage on warfarin. However, a large gap developed at follow‐up precluding warfarin cessation. To the best of our knowledge, this case report represents the first description of the use of a Gore® Helex® Septal Occluder (W. L. Gore and Associates, Newark, Delaware) as a novel approach to close a gap following percutaneous LAA suture ligation. © 2013 Wiley Periodicals, Inc.
Complex cytogenetic rearrangements at the DURS1 locus in syndromic Duane retraction syndrome
Authors: Baris Hagit N. , Chan Wai‐Man , Andrews Caroline , Behar Doron M. , Donovan Diana J. , Morton Cynthia C. , Ranells Judith , Pal Tuya , Ligon Azra H. , Engle Elizabeth C.
Published: October 2013

Key Clinical Message

A patient with syndromic Duane retraction syndrome harbors a chromosome 811.1q13.2 inversion and 8p11.1‐q12.3 marker chromosome containing subregions with differing mosaicism and allele frequencies. This case highlights the potential requirement for multiple genetic methods to gain insight into genotype–phenotype correlation, and ultimately into molecular mechanisms that underlie human disease.
Prenatal diagnosis of complex rearrangement of chromosome 21: The significance of interphase and metaphase fluorescence in situ hybridization and comparative genomic hybridization
Authors: Namba Akira , Nishiyama Miyuki , Weiser Joseph J , Wyatt Phillip , Kimura Machiko , Niizawa Rei , Miki Akinori , Ishihara Osamu , Itakura Atsuo , Kamei Yoshimasa
Published: October 2013

Key Clinical Message

Maternal serum screening–positive patient had prenatal diagnosis with amniotic fluid, which showed inconsistent results between interphase fluorescence in situ hybridization (three signals of 21q22.13‐21q22.2) and G‐banding analysis (46,XY). Further analyses proved that the fetus had extremely complex rearrangements of chromosome 21, including the interstitial duplication of Down syndrome critical region.
Confinement of Metal Nanoparticles in Carbon Nanotubes
Authors: Trang Nguyen T. , Serp Philippe
Published: October 2013

The effect of several parameters that include carbon nanotube (CNT) pretreatment and diameter, and the nature of the metal (Co, Ru, Pd), the metal precursor (nitrate, chloride, organometallic complexes), and the solvent on the filling yield of metallic nanoparticles in CNT channels is reported. The obtained results show that it is possible to modulate the filling yield between 10 and 80 % by controlling the CNT opening and playing on the molecular recognition of the inner/outer surfaces by the metal molecular precursor. Interestingly, the best filling yields have been obtained on nitric acid oxidized nanotubes; a treatment often used for the preparation of most CNT‐supported metal catalysts. The confined nanoparticles systematically show a smaller particle size than those supported on the external surface. All the prepared samples were tested for the selective hydrogenation of cinnamaldehyde, and clear correlations were established between the catalytic performances and the filling yields.
Oxidative Additions of Aryl Halides to Palladium Proceed through the Monoligated Complex
Authors: Vikse Krista , Naka Tsuki , McIndoe J. Scott , Besora Maria , Maseras Feliu
Published: October 2013

Palladium(0) complexes facilitate many catalytic transformations that begin with the oxidative addition of a halobenzene. The ligation state of the palladium during this reaction is a vexing issue, owing to the inherent difficulty of isolating reactive, coordinatively unsaturated metal complexes. By isolating them in the gas phase in an ion‐trap mass spectrometer, the reactivity of mono‐ and bisligated palladium complexes can be directly compared, and the former proved to be several orders of magnitude more reactive towards halobenzenes. Calculations of barrier heights for the oxidative addition led to additional experiments, which demonstrated that although the reaction proceeded to completion for iodobenzene, the reaction was slower for bromobenzene and progressed only as far as an ion–molecule adduct for chloro‐ and fluorobenzene.