bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe Energy Costs of Double Steric Interactions: Towards a Molecular Clamp
Authors: Nikitin Kirill , Fleming Conor , Müller‐Bunz Helge , Ortin Yannick , McGlinchey Michael J.
Published: August 2010

The factors determining the ease of rotation about carbon–carbon single bonds connecting two internally rigid fragments such as phenyl, indenyl, anthracenyl and triptycyl are analysed. The internal rotation barriers in these molecules have been estimated on the basis of kinetic data or variable‐temperature NMR measurements, and the crystal structures have been analysed in terms of steric strain. Computer simulation of the internal rotation indicates that the estimated Closest Approach Distance, CAD, between sterically interacting atoms of the two interconnected fragments can be a helpful parameter for evaluating their rotational freedom, but must be used with caution. Thus, the barrier to rotation of a 3‐indenyl moiety linked to the 9‐position of anthracene is very high (ΔG≠ ≈ 25 kcal mol–1) compared to that in 3‐indenyltriptycene (ΔG≠ ≈ 12 kcal mol–1) despite the fact that the nominal CADs in both cases are very similar. Moreover, dimeric 2‐methylindenyl fragments linked by a single bond at the 3‐position undergo relatively slow rotation (ΔG≠ ≈ 14–15 kcal mol–1) owing to the simultaneous close approach of two pairs of sterically interacting hydrogens. Although the rotational barrier for a 2‐indenyl or phenyl moiety attached to the bridgehead atom of triptycene, or to the related dibenzobicyclo[2.2.2]octane system, is relatively low (ΔG≠ ≈ 8–9 kcal mol–1), further extension of the bridge to dibenzobicyclo[2.2.4]dioxadecane leads to an activation energy barrier in excess of 23 kcal mol–1, attributable to an intramolecular simultaneous “clamping” of the phenyl rings by the edges of the aromatic rings of the dibenzobicyclo[2.2.4]dioxadecane moiety. The X‐ray crystal structures of 15 molecules, including mono‐ and di‐indenyl‐anthracenes, racemic‐ and meso‐2‐methylindenyl dimers, phenyl‐ and indenyl‐triptycenes and ‐barrelenes, are reported.
Solvent‐Free Chemoselective Cyanation of α,α‐Dibromoacetophenones Using Potassium Hexacyanoferrate(II) as an Eco‐Friendly Cyanide Source
Authors: Zhao Zhouxing , Li Zheng
Published: August 2010

A chemoselective route for the synthesis of 2‐aryl‐3,3‐dibromoacrylonitriles by solvent‐free cyanation of α,α‐dibromoacetophenones by using potassium hexacyanoferrate(II) as an eco‐friendly cyanide source is developed. The merits of this procedure include avoiding the use of a strong toxic cyanide source, a catalyst, and volatile organic solvents and the high yields of the products.
Convenient Synthesis of Tetrahydro‐γ‐carbolines and Tetrahydroquinolines through a Chemo‐ and Regioselectivity Switch by a Brønsted Acid Catalyzed, One‐Pot, Multicomponent Reaction
Authors: Cheng Hong‐Gang , Chen Cai‐Bao , Tan Fen , Chang Ning‐Jie , Chen Jia‐Rong , Xiao Wen‐Jing
Published: August 2010

An efficient, one‐pot, multicomponent reaction of aldehydes 1, p‐methoxyaniline (2a), and 2‐vinylindoles 3 was developed. This approach provides a practical approach to synthetically and biologically significant tetrahydro‐γ‐carboline and tetrahydroquinoline derivatives in good yields through a chemo‐ and regioselectivity switch, which can be tuned by simply changing the substituent on the indole component under identical reaction conditions.
A Cyclic Porphyrin Tetramer Linked by Azo and Butadiyne Bridges (Eur. J. Org. Chem. 23/2010)
Authors: Bašić Bruno , McMurtrie John C. , Arnold Dennis P.
Published: August 2010

The cover picture shows the tetranickel complex of a rectangular porphyrin array with novel connectivity. Conjugating azo and butadiyne bridges link the opposite sides of the rectangle, and the absorption spectrum demonstrates strong electronic communication between the chromophores. The synthesis and characterisation of this tetramer are described in the article by D. P. Arnold et al. on p. 4381 f. The molecule is set against a background of a sunset on the Great Barrier Reef, emphasising the role of porphyrinoid pigments in solar energy capture.
Protein phosphorylation in mitochondria – A study on fermentative and respiratory growth ofSaccharomyces cerevisiae
Authors: Ohlmeier Steffen , Hiltunen J. Kalervo , Bergmann Ulrich
Published: August 2010

Phosphorylation as a posttranslational protein modification is a common subject of proteomic studies, but phosphorylation in mitochondria is still poorly investigated. The study presented here applied 2‐DE to characterize phosphorylation in the yeast mitochondrial proteome and identified 59 spots corresponding to 34 phosphorylated mitochondrial or mitochondria‐associated proteins. Most of these proteins presented putative substrates of mitogen‐activated protein and target of rapamycin kinases, cAMP‐dependent protein kinase, cyclin‐dependent kinases and Snf1p suggesting them as key players in the phosphorylation of mitochondrial or mitochondria‐associated proteins. The dynamic behaviour of the phosphoproteome under a major metabolic change, the shift from fermentation to respiration (diauxic shift), was further studied. Eight proteins (Ald4p, Eft1p/2p, Eno1p, Eno2p, Om14p, Pda1p, Qcr2p, Sdh1p) had growth dependent changes in their phosphorylation, indicating a role of phosphorylation‐dependent regulation of translation, metabolic pathways (e.g.glucose fermentation, tricarboxylic acid cycle, pyruvate dehydrogenase and its bypass) and respiratory chain.
Construction of two fluorescence‐labeled non‐combined DNA index system miniSTR multiplex systems to analyze degraded DNA samples in the Chinese Han Population
Authors: Bai Xue , Li Shujin , Cong Bin , Li Xia , Guo Xia , He Lujun , Ye Jian , Pei Li
Published: August 2010

MiniSTR loci have been demonstrated to be an effective approach in recovering genetic information from degraded specimens, because of the reduced PCR amplicon sizes which improved the PCR efficiency. Eight non‐combined DNA index system miniSTR loci suitable for the Chinese Han Population were analyzed in 300 unrelated Chinese Han individuals using two novel five fluorescence‐labeled miniSTR multiplex systems(multiplex I: D10S1248, D2S441, D1S1677 and D9S2157; multiplex II: D9S1122, D10S1435, D12ATA63, D2S1776 and Amelogenin). The allele frequency distribution and forensic parameters in the Chinese Han Population were reported in this article. The Exact Test demonstrated that all loci surveyed here were found to be no deviation from Hardy–Weinberg equilibrium. The accumulated power of discrimination and power of exclusion for the eight loci were 0.999999992 and 0.98, respectively. The highly degraded DNA from artificially degraded samples and the degraded forensic case work samples was assessed with the two miniSTR multiplex systems, and the results showed that the systems were quite effective.
Lamp‐based wavelength‐resolved fluorescence detection for protein capillary electrophoresis: Setup and detector performance
Authors: de Kort Bregje J. , de Jong Gerhardus J. , Somsen Govert W.
Published: August 2010

A lamp‐based fluorescence detection (Flu) system for CE was extended with a wavelength‐resolved (WR) detector to allow recording of full protein emission spectra. WRFlu was achieved using a fluorescence cell that employs optical fibres to lead excitation light from a Xe‐Hg lamp to the capillary window and protein fluorescence emission to a spectrograph equipped with a CCD. A 280 nm band pass filter etc. together with a 300 nm short pass cut‐off filter was used for excitation. A capillary cartridge was modified to hold the detection cell in a commercial CE instrument enabling WRFlu in routine CE. The performance of the WRFlu detection was evaluated and optimised using lysozyme as model protein. Based on reference spectral data, a signal‐intensity adjustment was introduced to correct for transmission losses in the detector optics that occurred for lower protein emission wavelengths. CE‐WRFlu of lysozyme was performed using BGEs of 50 mM sodium phosphate (pH 6.5 or 3.0) and a charged‐polymer coated capillary. Using the 3‐D data set, signal averaging over time and emission‐wavelength intervals was carried out to improve the S/N of emission spectra and electropherograms. The detection limit for lysozyme was 21 nM, providing sufficient sensitivity to obtain spectral information on protein impurities.
Sample stacking capillary electrophoretic microdevice for highly sensitive mini Y short tandem repeat genotyping
Authors: Chen Yuchao , Choi Jong Young , Choi Seok Jin , Seo Tae Seok
Published: August 2010

Lab‐on‐a‐chip provides an ideal platform for short tandem repeat (STR) genotyping due to its intrinsic low sample consumption, rapid analysis, and high‐throughput capability. One of the challenges, however, in the forensic human identification on the microdevice is the detection sensitivity derived from the nanoliter volume sample handling. To overcome such a sensitivity issue, here we developed a sample stacking CE microdevice for mini Y STR genotyping. The mini Y STR includes redesigned primer sequences to generate smaller‐sized PCR amplicons to enhance the PCR efficiency and the success rate for a low copy number and degraded DNA. The mini Y STR amplicons occupied in the 5‐ and 10‐mm stacking microchannels are preconcentrated efficiently in a defined narrow region through the optimized sample stacking CE scheme, resulting in more than tenfold improved fluorescence peak intensities compared with that of a conventional cross‐injection microcapillary electrophoresis method. Such signal enhancement allows us to successfully analyze the Y STR typing with only 25 pg of male genomic DNA, with high background of female genomic DNA, and with highly degraded male genomic DNA. The combination of the mini Y STR system with the novel sample stacking CE microdevice provides the highly sensitive Y STR typing on a chip, making it promising to perform high‐performance on‐site forensic human identification.
Covariance precoding schemes for MIMO OFDM over transmit‐antenna and path‐correlated channels
Authors: Fu Yu , Krzymień Witold A. , Tellambura Chintha
Published: August 2010

This paper considers covariance‐feedback based linear precoding (LP) and nonlinear Tomlinson–Harashima precoding (THP) for multiple‐input multiple‐output (MIMO) orthogonal frequency‐division multiplexing (OFDM) systems. Orthogonal space–time block coded (OSTBC)‡OFDM and spatially‐multiplexed (SM)§OFDM are analysed. The main objective is to design precoders to mitigate the impact of transmit‐antenna and path correlations. The impact of path correlations on the pairwise error probability (PEP) of MIMO OFDM is also analysed. Closed‐form, waterfilling‐based covariance precoders are derived to minimize the worst case PEP in OSTBC OFDM. An adaptive transmission strategy is also developed for switching between precoded SM OFDM and precoded OSTBC OFDM. The switching criterion is the minimum Euclidean distance of the received codebook. The switching decision sent to the transmitter requires one feedback bit per subcarrier. The proposed precoders considerably reduce the error rate in antenna and path‐correlated channels; nonlinear precoders perform better than linear precoders. We show that the adaptive strategy can achieve full diversity gain, and it outperforms either SM or OSTBC applied individually in terms of the bit error rate (BER). Copyright © 2010 John Wiley & Sons, Ltd.
Inhibitory stimulation of the ventral premotor cortex temporarily interferes with musical beat rate preference
Authors: Kornysheva Katja , von Anshelm‐Schiffer Anne‐Marike , Schubotz Ricarda I.
Published: August 2010

Behavioral studies suggest that preference for a beat rate (tempo) in auditory sequences is tightly linked to the motor system. However, from a neuroscientific perspective the contribution of motor‐related brain regions to tempo preference in the auditory domain remains unclear. A recent fMRI study (Kornysheva et al. [2010]: Hum Brain Mapp 31:48‐64) revealed that the activity increase in the left ventral premotor cortex (PMv) is associated with the preference for a tempo of a musical rhythm. The activity increase correlated with how strongly the subjects preferred a tempo. Despite this evidence, it remains uncertain whether an interference with activity in the left PMv affects tempo preference strength. Consequently, we conducted an offline repetitive transcranial magnetic stimulation (rTMS) study, in which the cortical excitability in the left PMv was temporarily reduced. As hypothesized, 0.9 Hz rTMS over the left PMv temporarily affected individual tempo preference strength depending on the individual strength of tempo preference in the control session. Moreover, PMv stimulation temporarily interfered with the stability of individual tempo preference strength within and across sessions. These effects were specific to the preference for tempo in contrast to the preference for timbre, bound to the first half of the experiment following PMv stimulation and could not be explained by an impairment of tempo recognition. Our results corroborate preceding fMRI findings and suggest that activity in the left PMv is part of a network that affects the strength of beat rate preference. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.
Effective connectivity of the multiplication network: A functional MRI and multivariate granger causality mapping study
Authors: Krueger Frank , Landgraf Steffen , van der Meer Elke , Deshpande Gopikrishna , Hu Xiaoping
Published: August 2010

Developmental neuropsychology and functional neuroimaging evidence indicates that simple and complex mental calculation is subserved by a fronto‐parietal network. However, the effective connectivity (connection direction and strength) among regions within the fronto‐parietal network is still unexplored. Combining event‐related fMRI and multivariate Granger Causality Mapping (GCM), we administered a multiplication verification task to healthy participants asking them to solve single and double‐digit multiplications. The goals of our study were first, to identify the effective connectivity of the multiplication network, and second, to compare the effective connectivity patterns between a low and a high arithmetical competence (AC) group. The manipulation of multiplication difficulty revealed a fronto‐parietal network encompassing bilateral intraparietal sulcus (IPS), left pre‐supplementary motor area (PreSMA), left precentral gyrus (PreCG), and right dorsolateral prefrontal cortex (DLPFC). The network was driven by an intraparietal IPS‐IPS circuit hosting a representation of numerical quantity intertwined with a fronto‐parietal DLPFC‐IPS circuit engaged in temporary storage and updating of arithmetic operations. Both circuits received additional inputs from the PreCG and PreSMA playing more of a supportive role in mental calculation. The high AC group compared to the low AC group displayed a greater activation in the right IPS and based its calculation more on a feedback driven intraparietal IPS‐IPS circuit, whereas the low competence group more on a feedback driven fronto‐parietal DLPFC‐IPS circuit. This study provides first evidence that multivariate GCM is a sensitive approach to investigate effective connectivity of mental processes involved in mental calculation and to compare group level performances for different populations. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
Framework and methodology for evaluating mental health policy and plans
Authors: Funk Michelle , Freeman Melvyn
Published: August 2010

The importance of monitoring and evaluation for mental health service planning and delivery is indubitable. Notwithstanding, monitoring and evaluation of mental health policy and plans has received only limited attention. This paper presents an approach developed by the World Health Organization for monitoring mental health policy and plans that can be adapted and utilized for evaluation and monitoring of policy and plans in most other health spheres as well. Four critical areas are outlined i.e., evaluation of the policy document and the plan derived from it; monitoring the implementation of the strategic plan; evaluation of the implementation of the plan; and evaluation of whether the objectives of the policy have been achieved. Overcoming difficulties in objective assessment of policy documents and plans is discussed and two WHO checklists for evaluating the process, content and operational aspects of policies and plans are introduced together with a five step guidance process for conducting policy and plan evaluations. Copyright © 2010 John Wiley & Sons, Ltd.
Retracted: Norepinephrine induces VEGF expression and angiogenesis by a hypoxia‐inducible factor‐1α protein‐dependent mechanism
Authors: Park Soon Young , Kang Joo Hee , Jeong Kang Jin , Lee Jangsoon , Han Jeong Whan , Choi Wahn Soo , Kim Yong Kee , Kang Jaeku , Park Chang Gyo , Lee Hoi Young
Published: August 2010

A growing number of studies have demonstrated that physiological factors can influence the progression of several cancers via cellular immune function, angiogenesis and metastasis. Recently, stress‐induced catecholamines have been shown to increase the expression of various cancer progressive factors, including vascular endothelial growth factor (VEGF), matrix metalloproteinases and interleukins. However, a detailed mechanism remains to be identified. In this study, we investigated the role of adrenergic receptors and hypoxia‐inducible factor (HIF)‐1α protein in catecholamine‐induced VEGF expression and angiogenesis. Treatment of the cells with norepinephrine (NE) or isoproterenol induced VEGF expression and HIF‐1α protein amount in a dose‐dependent manner. Induction of VEGF expression by NE was abrogated when the cells were transfected with HIF‐1α–specific siRNA. Similarly, adenylate cyclase activator forskolin and cyclic AMP‐dependent protein kinase A inhibitor H‐89 enhanced and decreased HIF‐1α protein amount, respectively. More importantly, conditioned medium of NE‐stimulated cancer cells induced angiogenesis in a HIF‐1α protein–dependent manner. In addition, pretreatment of cells with propranolol, a β‐adrenergic receptor (AR) blocker, completely abolished induction of VEGF expression and HIF‐1α protein amount by NE in all of the tested cancer cells. However, treatment with the α1‐AR blocker prazosin inhibited NE‐induced HIF‐1α protein amount and angiogenesis in SK‐Hep1 and PC‐3 but not MDA‐MB‐231 cells. Collectively, our results suggest that ARs and HIF‐1α protein have critical roles in NE‐induced VEGF expression in cancer cells, leading to stimulation of angiogenesis. These findings will help to understand the mechanism of cancer progression by stress‐induced catecholamines and design therapeutic strategies for cancer angiogenesis.
Decreased expression of updated NESG1 in nasopharyngeal carcinoma: Its potential role and preliminarily functional mechanism
Authors: Liu Zhen , Li Xin , He Xiufang , Jiang Qingping , Xie Siming , Yu Xiaoli , Zhen Yan , Xiao Guanghui , Yao Kaitai , Fang Weiyi
Published: August 2010

Human NESG1 (CCDC19) gene was originally isolated in our laboratory from human nasopharynx tissue. However, the biological and clinical significances of this gene remain largely unknown. In this report, two errors in the originally submitted sequence of human NESG1 gene were found, and the open reading frame sequence of NESG1 (Accession number: NM_012337.1) was revised and updated in the NCBI database (Accession number: NM_012337.2). The antibody raised against the revised sequence of NESG1 detected a single band of 66 kD in human nasopharynx tissues. NESG1 transcripts were specifically expressed in the nasopharynx epithelium. Expression of NESG1 transcripts and protein was downregulated or absent in nasopharyngeal carcinoma (NPC) tissues and cell lines in comparison to that in the normal nasopharynx tissues. The levels of NESG1 protein were significantly greater in the low‐grade NPC tissues than that in the high‐grade NPC tissues. Induced expression of NESG1 in otherwise NESG1‐negative 5‐8F cells not only significantly decreased cell proliferation, G1‐S phase transition, but also markedly inhibited the ability of cell migration and invasion as well as in vivo tumorigenesis. Furthermore, NESG1 also significantly regulated the expression of cell cycle regulator CCNA1 and p21. Our findings first provided evidence that NESG1 may act as a tumor suppressor by inhibiting cell proliferation, invasion and migration of NPC cells.
Predictors and survival of synchronous peritoneal carcinomatosis of colorectal origin: A population‐based study
Authors: Lemmens Valery E. , Klaver Yvonne L. , Verwaal Vic J. , Rutten Harm J. , Coebergh Jan Willem W. , de Hingh Ignace H.
Published: August 2010

The aim of our study was to provide population‐based data on incidence and prognosis of synchronous peritoneal carcinomatosis and to evaluate predictors for its development. Diagnosed in 1995–2008, 18,738 cases of primary colorectal cancer were included. Predictors of peritoneal carcinomatosis were analysed by multivariable logistic regression analysis. Median survival in months was calculated by site of metastasis. In the study period, 904 patients were diagnosed with synchronous peritoneal carcinomatosis (4.8% of total, constituting 24% of patients presenting with M1 disease). The risk of peritoneal carcinomatosis was increased in case of advanced T stage [T4 vs. T1,2: odds ratio (OR) 4.7, confidence limits 4.0–5.6), advanced N stage [N0 vs. N1,2: OR 0.2 (0.1–0.2)], poor differentiation grade [OR 2.1 (1.8–2.5)], younger age [<60 years vs. 70–79 years: OR 1.4 (1.1–1.7)], mucinous adenocarcinoma [OR 2.0 (1.6–2.4)] and right‐sided localisation of primary tumour [left vs. right: OR 0.6 (0.5–0.7)]. Median survival of patients with peritoneum as single site of metastasis remained dismal [1995–2001: 7 (6–9) months; 2002–2008: 8 (6–11) months], contrasting the improvement among patients with liver metastases [1995–2001: 8 (7–9) months; 2002–2008: 12 (11–14) months]. To conclude, synchronous peritoneal metastases from colorectal cancer are more frequent among younger patients and among patients with advanced T stage, mucinous adenocarcinoma, right‐sided tumours and tumours that are poorly differentiated. The prognosis of synchronous peritoneal carcinomatosis remains poor with a median survival of 8 months and even worse if concomitant metastases in other organs are present.
Dietary acrylamide intake and risk of esophageal cancer in a population‐based case‐control study in Sweden
Authors: Lin Yulan , Lagergren Jesper , Lu Yunxia
Published: August 2010

Acrylamide is a potential carcinogen, which commonly occurs in some food items. The relation between acrylamide and esophageal cancer deserves attention. In a Swedish nationwide, population‐based case‐control study, data were collected on diet among other variables in 1995–1997 through personal interviews. Included were 189 cases of esophageal adenocarcinoma (participation rate 88%), 262 cases of gastroesophageal junctional adenocarcinoma (84%), 167 cases of esophageal squamous cell carcinoma (73%), and 820 control participants (73%). Dietary intake of acrylamide exposure was assessed from a food‐frequency questionnaire and categorized into quartiles based on the consumption among the control participants. Unconditional logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI), with multivariable adjustment for known risk factors. Among participants in the highest quartile of acrylamide exposure compared to the lowest, the adjusted risk of all esophageal tumors combined was increased (OR 1.23; 95% CI 1.02–1.75), particularly among overweight or obese persons (OR 1.88; 95% CI 1.06–3.34). Increased point risk estimates were found for each type of esophageal cancer, but the association with esophageal squamous cell carcinoma seemed stronger and was statistically significant, particularly among nonsmokers in the highest quartile of acrylamide exposure (adjusted OR 2.82; 95% CI 1.16–6.87). Regarding squamous cell carcinoma only, a dose‐response association was identified (p for trend 0.01). Dietary intake of acrylamide might be a risk exposure for esophageal cancer, a stronger association among overweight or obese persons was indicated.
NADPH oxidase overexpression in human colon cancers and rat colon tumors induced by 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP)
Authors: Wang Rong , Dashwood Wan‐Mohaiza , Nian Hui , Löhr Christiane V. , Fischer Kay A. , Tsuchiya Naoto , Nakagama Hitoshi , Ashktorab Hassan , Dashwood Roderick H.
Published: August 2010

NADPH oxidase/dual‐oxidase (Nox/Duox) family members have been implicated in nuclear factor kappa‐B (NFκB)‐mediated inflammation and inflammation‐associated pathologies. We sought to examine, for the first time, the role of Nox/Duox and NFκB in rats treated with the cooked meat heterocyclic amine carcinogen 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP). In the PhIP‐induced colon tumors obtained after 1 year, Nox1, Nox4, NFκB‐p50 and NFκB‐p65 were all highly overexpressed compared with their levels in adjacent normal‐looking colonic mucosa. Nox1 and Nox4 mRNA and protein levels also were markedly elevated in a panel of primary human colon cancers, compared with their matched controls. In HT29 human colon cancer cells, Nox1 knockdown induced G1 cell cycle arrest, whereas in Caco‐2 cells there was a strong apoptotic response, with increased levels of cleaved caspase‐3, ‐6, ‐7 and poly(ADP‐ribose)polymerase. Nox1 knockdown blocked lipopolysaccharide‐induced phosphorylation of IκB kinase, inhibited the nuclear translocation of NFκB (p50 and p65) proteins, and attenuated NFκB DNA binding activity. There was a corresponding reduction in the expression of downstream NFκB targets, such as MYC, CCND1 and IL1β. The results provide the first evidence for a role of Nox1, Nox4 and NFκB in PhIP‐induced colon carcinogenesis, including during the early stages before tumor onset. Collectively, the findings from this investigation and others suggest that further work is warranted on the role of Nox/Duox family members and NFκB in colon cancer development.
High‐throughput live‐cell imaging reveals differential inhibition of tumor cell proliferation by human fibroblasts
Authors: Flaberg Emilie , Markasz Laszlo , Petranyi Gabor , Stuber Gyorgy , Dicső Ferenc , Alchihabi Nidal , Oláh Èva , Csízy István , Józsa Tamás , Andrén Ove , Johansson Jan‐Erik , Andersson Swen‐Olof , Klein George , Szekely Laszlo
Published: August 2010

Increasing evidence indicates that cancer development requires changes both in the precancerous cells and in their microenvironment. To study one aspect of the microenvironmental control, we departed from Michael Stoker's observation (Stroker et al, J Cell Sci 1966;1:297–310) that normal fibroblasts can inhibit the growth of admixed cancer cells (neighbour suppression). We have developed a high‐throughput microscopy and image analysis system permitting the examination of live mixed cell cultures growing on 384‐well plates, at the single cell level and over time. We have tested the effect of 107 samples of low passage number (<5) primary human fibroblasts from pediatric and adult donors, on the growth of six human tumor cell lines. Three of the lines were derived from prostate carcinomas, two from lung carcinomas and one was an EBV‐transformed lymphoblastoid line. Labeled tumor cells were grown in the presence of unlabeled fibroblasts. The majority of the tested fibroblasts inhibited the proliferation of the tumor cells, compared to the control cultures where labeled tumor cells were co‐cultured with unlabeled tumor cells. The proliferation inhibiting effect of the fibroblasts differed depending on their site of origin and the age of the donor. Inhibition required direct cell contact. Mouse 3T3 fibroblasts inhibited the growth of SV40‐transformed 3T3 cells and human tumor cells, showing that the inhibitory effect could prevail across the species barrier. Our high‐throughput system allows the quantitative analysis of the inhibitory effect of fibroblasts on the population level and the exploration of differences depending on the source of the normal cells.
Rational Design of Multifunctional Polymer Therapeutics for Cancer Theranostics
Authors: Ofek Paula , Miller Keren , Eldar‐Boock Anat , Polyak Dina , Segal Ehud , Satchi‐Fainaro Ronit
Published: August 2010

Although anti‐angiogenic agents offer great therapeutic potential, preclinical and clinical studies suggest that these agents, used as monotherapies, have a delayed onset of activity and may have only limited effects on advanced malignancies. Multimodality targeted polymer therapeutics that include anti‐angiogenic agents and chemotherapeutics offer the potential for improved efficacy and diminished toxicity in the treatment of cancer and other angiogenesis‐dependent diseases. We have recently designed and characterized novel combined anti‐angiogenic and antitumor polymer–drug conjugates that target both the tumor and its microenvironment. These conjugates include combined anti‐angiogenic and chemotherapeutic drugs, such as TNP‐470 and paclitaxel, respectively. Several conjugates also incorporate bisphosphonates as targeting moieties for bone metastases and osteosarcomas or RGD peptidomimetics that target integrins overexpressed on tumor endothelial cells and several tumor cells. Using molecular imaging techniques, we have successfully established dormant and fast‐growing tumor mouse models to intravitally non‐invasively follow‐up tumor progression and response to novel polymer therapeutics. Our results point at our polymer therapeutics as novel bi‐specific conjugates targeting both the tumor epithelial and endothelial compartments, warranting their use on a wide spectrum of primary as well as metastatic tumors. The use of these novel architectures will potentially shed light on the molecular mechanisms underlying tumor dormancy and hopefully transform cancer into a chronically‐manageable disease.
Comparative study of tumor hypoxia by diffuse optical spectroscopy and immunohistochemistry in two tumor models
Authors: Maslennikova Anna V. , Orlova Anna G. , Golubiatnikov German Yu. , Kamensky Vladislav A. , Shakhova Natalia M. , Babaev Aleksey A. , Snopova Ludmila B. , Ivanova Irina P. , Plekhanov Vladimir I. , Prianikova Tatyana I. , Turchin Ilya V.
Published: August 2010

The capabilities of diffuse optical spectroscopy for noninvasive assessing of oxygen status in experimental tumors have been demonstrated. Specific features of the distribution of total hemoglobin, oxygenated hemoglobin, deoxygenated hemoglobin, and blood‐oxygen saturation were shown on two tumor models having different histological structure and functional characteristics. The results obtained by the optical technique were verified by immunohistochemical study of tissue samples marked with exogenous marker of hypoxia – pimonidazole. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Clinical application of multiphoton tomography in combination with high‐frequency ultrasound for evaluation of skin diseases
Authors: König Karsten , Speicher Marco , Köhler Martin J. , Scharenberg Rüdiger , Kaatz Martin
Published: August 2010

The first‐ever application of high‐frequency ultrasound combined with multiphoton tomography (MPT) and dermoscopy in a clinical trial is reported. 47 patients with different dermatoses such as benign and malign skin cancers, connective tissue diseases, inflammatory skin diseases, and autoimmune bullous skin diseases have been investigated with (i) state‐of‐the‐art and highly sophisticated ultrasound systems for dermatology, (ii) the femtosecond laser multiphoton tomograph and (iii) dermoscopes. Dermoscopy provides two‐dimensional color images of the skin surface with a magnification up to 70×. Depending on the ultrasonic frequencies from 7.5 MHz to 100 MHz, the signal depth varies from about 1 mm to 80 mm. Vertical ultrasound wide‐field images provide fast information on depth and volume of the lesion. The 100 MHz ultrasound allows imaging with resolutions down to 16 μm (axial) and 32 μm (lateral). Multiphoton tomography provides 0.36 × 0.36 × 0.001 mm3 horizontal optical sections of a particular region of interest with submicron resolution down to 200 μm tissue depth. The autofluorescence of mitochondrial coenzymes, keratin, melanin, and elastin as well as the network of collagen structures can be imaged. The combination of ultrasound and MPT opens novel synergistic possibilities in diagnostics of skin diseases with a special focus on the early detection of skin cancer as well as the evaluation of treatments. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Osteoblast-specific expression of MEF induces osteopenia through downregulation of osteoblastogenesis and upregulation of osteoclastogenesis
Authors: Seul Keyung-Jo , Cho Hye-Sim , Heo Sun-Hee , Baek Wook-Young , Kim Jung-Eun , Park Eui Kyun , Choi Je-Yong , Ryoo Hyun-Mo , Cho Je-Yoel
Published: August 2010

In bone remodeling, various transcriptional factors are involved, and the deficiency or overexpression of some of these factors results in bone defects. Myeloid elf-1-like factor (MEF) is one of the Ets transcription factors that control the expression of genes that are critical for biologic processes such as cell proliferation, differentiation, and death. Previously, we reported that MEF promotes cell proliferation and functions as a negative regulator of osteogenic differentiation by interacting directly with Runx2 and suppressing its transcriptional activity. To investigate the in vivo function of MEF in bone formation and bone remodeling in vivo, we generated transgenic mice that overexpress MEF in osteoblasts under the control of the 2.3-kb Col1α1 promoter, named Col1α1-MEF. Femoral bone in Col1α1-MEF transgenic mice exhibited low bone mass with fewer trabecular bones and thinner and less developed cortical bones. The mineralized volume fraction (BV/TV) and bone-forming rate (BFR) were remarkably decreased to about 63% and 40%, respectively, in 6-week-old MEF transgenic mice compared with wild-type mice. In addition, reduced bone mineral density was observed in lumbar vertebrae of Col1α1-MEF transgenic mice. The number of TRACP+ osteoclasts was increased in Col1α1-MEF transgenic mice and MEF-overexpressing MC3T3-E1 cells. All these in vivo results suggest that MEF suppresses bone formation by osteoblasts and facilitates bone resorption by activating osteoclasts indirectly. © 2011 American Society for Bone and Mineral Research.
Recycling and LFA‐1‐dependent trafficking of ICAM‐1 to the immunological synapse
Authors: Jo Jae‐Hyeok , Kwon Min‐Sung , Choi Hyang‐Ok , Oh Hyun‐Mee , Kim Hyang‐Jin , Jun Chang‐Duk
Published: August 2010

Little is known about how adhesion molecules on APCs accumulate at immunological synapses. We show here that ICAM‐1 on APCs is continuously internalized and rapidly recycled back to the interface after antigen‐priming T‐cell contact. The internalization rate is high in APCs, including Raji B cells and dendritic cells, but low in endothelial cells. Internalization is significantly reduced by inhibitors of Na+/H+ exchangers (NHEs), suggesting that members of the NHE‐family regulate this process. Once internalized, ICAM‐1 is co‐localized with MHC class II in the polarized recycling compartment. Surprisingly, not only ICAM‐1, but also MHC class II, is targeted to the immunological synapse through LFA‐1‐dependent adhesion. Cytosolic ICAM‐1 is highly mobile and forms a tubular structure. Inhibitors of microtubule or actin polymerization can reduce ICAM‐1 mobility, and thereby block accumulation at immunological synapses. Membrane ICAM‐1 also moves to the T‐cell contact zone, presumably through an active, cytoskeleton‐dependent mechanism. Collectively, these results demonstrate that ICAM‐1 can be transported to the immunological synapse through the recycling compartment. Furthermore, the high‐affinity state of LFA‐1 on T cells is critical to induce targeted movements of both ICAM‐1 and MHC class II to the immunological synapse on APCs. J. Cell. Biochem. 111: 1125–1137, 2010. © 2010 Wiley‐Liss, Inc.
Reynolds adolescent depression scale‐second edition: a reliable and useful instrument
Authors: Osman Augustine , Gutierrez Peter M. , Bagge Courtney L. , Fang Qijuan , Emmerich Ashley
Published: August 2010

The authors conducted two studies to address issues of the dimensionality, scale reliability, and psychometric properties of scores on the Reynolds Adolescent Depression Scale‐Second Edition (RADS‐2; Reynolds, 2002) in samples of adolescent psychiatric inpatients. In Study 1 (N=262), they used bifactor analysis to further evaluate the general and specific components of the RADS‐2. In Study 2 (N=196), they used confirmatory factor analysis to evaluate the fit of a 1‐factor model, the original 4‐factor model, a second‐order model, and a bifactor model to a new sample data. In both studies, the total RADS‐2 and content‐specific subscale scores showed acceptable estimates of reliability (i.e., scale reliability estimates >.80). Estimates of concurrent validity were also examined. Scores of the RADS‐2 total and content‐specific subscale scores were useful in differentiating between the responses of youth with mood disorder diagnoses and those with other primary psychiatric disorder diagnoses. The authors also conducted correlation analyses to identify potential correlates for the total RADS‐2 scale and the proposed subscale scores. © 2010 Wiley Periodicals, Inc. J Clin Psychol 66:1–22, 2010.
Morphology and posthatching ontogeny of the autopodial skeleton of Bolitoglossa nicefori (Caudata: Plethodontidae)
Authors: Cabrera‐Téllez Laura , Tarazona Oscar A. , Ramírez‐Pinilla Martha Patricia
Published: August 2010

Webbed foot morphology is a highly homoplastic character in species of Bolitoglossa and has been assumed to be pedomorphic. This study examines the morphology and posthatching ontogeny of the autopodial skeleton of Bolitoglossa nicefori and compares the descriptive and morphometric results with other species of the genus. We show that the autopodial morphology of B. nicefori coincides with the generalized pattern of the genus; webbed foot morphology is produced by pedomorphosis that affect the phalange length of the digits, resulting in a synchronized growth of digits (length and ossification rates) and the fleshy web. Although the webbed foot morphology of B. nicefori might be explained by the pervasive pedomorphic developmental trend observed in the genus, the large degree of variation encountered in the morphology of the distal phalanges indicates that the pedomorphic processes acting in this species are neither a simple truncation of the autopodial developmental program during early posthatching development nor a global process acting over the whole body plan. Instead, this morphological pattern is probably a result of the modular nature of limb development. J. Morphol., 2010. © 2010 Wiley‐Liss, Inc.
Global climate change and its impacts on the terrestrial Arctic carbon cycle with special regards to ecosystem components and the greenhouse‐gas balance
Authors: Jahn Markus , Sachs Torsten , Mansfeldt Tim , Overesch Mark
Published: August 2010

The climatic changes on earth may have serious implications for the carbon (C) cycle in the terrestrial Arctic throughout the 21st century. Arctic vegetation takes up carbon dioxide (CO2) from the atmosphere producing biomass. In a cold and often moist soil environment, dead organic matter is preferentially preserved as soil organic matter (SOM) due to the inhibition of decomposition processes. However, viable soil microbes exhale huge amounts of CO2 and methane (CH4) annually. Hence, Arctic ecosystems exhibit annual fluxes of both carbon‐based (CO2 and CH4) greenhouse gases (GHGs) that are in an order of magnitude of millions of tons. Rising Arctic temperatures lead to the degradation of much of today's permafrost in the long run. As a result, large quantities of frozen SOM may become available for decomposers, and GHGs that are entrapped in permafrost may be released. At the same time, warming tends to stimulate the growth, development, and reproduction of many Arctic plants, at least transiently. The present northward migration of boreal shrubs and trees into southern tundra areas may be amplified by that, increasing the ecosystems' gross primary production and, thus, their C sequestration. On the other hand, rising temperatures boost SOM decomposition and microbial respiration rates. In general, soil temperature and soil moisture are key environmental variables to control the intensity of aerobic and anaerobic respiration by microbes, and autotrophic respiration by plants.

On the basis of published data on Arctic CO2 and CH4 fluxes, the calculations on the terrestrial C‐based Arctic GHG balance made in this review reveal a current annual GHG exchange that ranges between a weak storage of ≤ 225 Tg CO2 equivalent (eq.) y–1 and a huge release of ≤ 1990 Tg CO2 eq. y–1. Hence, the Arctic GHG balance does apparently already contribute positively to the climatic changes at present. Regarding the future, the relative development of the uptake and release of CO2 and CH4 by northern ecosystems is fundamental to the overall GHG status of the Arctic under scenarios of continued climate change.
The impact of silica gel pore and particle sizes on HPLC column efficiency and resolution for an immobilized, cyclodextrin‐based, chiral stationary phase
Authors: Qin Qing , Zhang Sheng , Zhang Wei‐Guang , Zhang Zhen‐Bin , Xiong Ya‐Jin , Guo Zi‐Yuan , Fan Jun , Run‐Zheng Sheng , Finlow David , Yin Yong
Published: August 2010

In this study, the CD derivative, mono (6A‐azido‐6A‐deoxy)‐per(p‐chlorophenylcarbamonylated) β‐CD was chemically immobilized onto the surface of an amino‐functionalized silica gel with different pore (100, 300, and 500Å) and particle (3, 5, and 10 μm) sizes to obtain novel chiral stationary phases. The impact of pore and particle size on the amount of immobilized Ph‐β‐CD, column performance, and enantioselectivity was investigated by evaluating the separation of a variety of racemates in both the normal‐ and the reversed‐phase modes. Experimental results revealed that the retention factor and resolution of racemates generally decreased with increasing pore size; the column prepared with the smallest (3 μm) silica gel particle size gave the best column performance and enantioselectivity in both the normal‐ and the reversed‐phase modes.
The influence of polymer concentration, applied voltage, modulation depth and pulse frequency on DNA separation by pulsed field CE
Authors: Li Zhenqing , Dou Xiaoming , Ni Yi , Sumitomo Keiko , Yamaguchi Yoshinori
Published: August 2010

DNA fragments (0.1–10 kbp (kbp, kilo base pair)) separation by square‐wave pulsed field CE in hydroxyethylcellulose (HEC, 1300 K) polymer was performed in this work. The effects of polymer concentration, pulse field strength, pulse frequency and modulation depth were investigated. We found that low HEC (about 0.1%) concentration is suitable for the separation of small DNA fragments (<1 kbp), whereas higher HEC concentration (>0.5%) is appropriated for high‐mass DNA molecular (>1 kbp) separation. The mobility of DNA fragments is nearly linearly related to average separation voltage under pulsed field conditions. Higher modulation depth is suited to separate the longer DNA fragments and lower modulation depth favors the resolution of short DNA fragments. Thus, the intermediate modulation depth (100%) and pulse frequency (about 31.3 Hz) are prerequisite for high‐resolution DNA separation.
Extension of the C18 stationary phase knowledge by using the carotenoid test
Authors: Lesellier Eric
Published: August 2010

The carotenoid test for octadecylsiloxane‐bonded stationary phases used in RPLC was developed some years ago. Additional experiments have now been performed with varied stationary phases. The effect of the bonding density and of the pore diameter on steric selectivity, polar surface activity and hydrophobicity was determined by using YMC series (J'Sphere and Pack ODSA). The test was also extended to estimate the phase evolution of several classical or hybrid silicas. The high loading phases were also studied, as well as the fused core silicas. The effect of the particle size reduction on the three previous phase properties was investigated in the goal to determine in which way this parameter could also modify the chemical properties of the phases.
Narrative exposure therapy for 7‐ to 16‐year‐olds: A randomized controlled trial with traumatized refugee children
Authors: Ruf Martina , Schauer Maggie , Neuner Frank , Catani Claudia , Schauer Elisabeth , Elbert Thomas
Published: August 2010

The authors examined the effectiveness of narrative exposure therapy for children (KIDNET) in treating posttraumatic stress disorder (PTSD) in refugee children living in exile. Twenty‐six children traumatized by organized violence were randomly assigned to KIDNET or to a waiting list. Significant treatment by time interactions on all PTSD‐relevant variables indicated that the KIDNET group, but not the controls, showed a clinically significant improvement in symptoms and functioning. Success of the KIDNET group remained stable at 12‐month follow‐up. This study confirms previous findings that, if left untreated, PTSD in children may persist for an extended period. However, it also shows that it is possible to effectively treat chronic PTSD and restore functioning in traumatized refugee children in only 8 treatment sessions.
Fear of anxiety as a partial mediator of the relation between trauma severity and PTSD symptoms
Authors: Reuther Erin T. , Davis III Thompson E. , Matthews Russell A. , Munson Melissa S. , Grills‐Taquechel Amie E.
Published: August 2010

Fear of anxiety has previously been found to be a predictor of overall symptoms of posttraumatic stress disorder (PTSD). The current exploratory study examines the relationship between fear of anxiety and symptoms of PTSD in a sample of adults exposed to Hurricane Katrina. Fear of anxiety was found to partially mediate the relationship between the severity of trauma and the severity of PTSD. Further, this mediation was found to operate differently by gender, with the mediation holding true for men but not for women. For both men and women, fear of anxiety was positively correlated with PTSD symptoms.
Synthesis of Linear Polyamines with Different Amine Spacings and their Ability to Form dsDNA/siRNA Complexes Suitable for Transfection
Authors: Fischer Wiebke , Brissault Blandine , Prévost Sylvain , Kopaczynska Marta , Andreou Ioanna , Janosch Andrea , Gradzielski Michael , Haag Rainer
Published: August 2010

In this paper we report on the synthesis of diversified linear polyamine architectures with different chain lengths and compositions and their interaction with phosphate groups of DNA/siRNA. The polyplex formation between model nucleotide (dsDNA) and these linear polyamines has been determined at different nitrogen to phosphorus (N/P) ratios using small‐angle neutron scattering (SANS) and atomic force microscopy (AFM) techniques. AFM images showed that while linear poly(ethylene imine) (PEI)/DNA complex results in bigger spherical aggregates, poly(propylene imine)s forms torroid and cigar shaped structures upon complexation with DNA. The poly(butylene imine)s (LPBI)s form compact and soluble DNA complexes with a radii range of Rg = 15–30 nm. Among the studied linear polyamines, the LPBIs did show the best transfection efficiency.

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