bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical strategies for non-functioning pancreatic neuroendocrine tumours
Authors: Kim M J , Choi D W , Choi S H , Heo J S , Park H J , Choi K K , Jang K-T , Sung J-Y
Published: October 2012

Background

The purpose of this study was to identify management strategies for non-functioning pancreatic neuroendocrine tumours (NF-PNETs) by analysis of surgical outcomes at a single institution.

Methods

Archived records of patients with NF-PNETs who underwent surgery between 1994 and 2010 were reviewed.

Results

Among 125 patients, the median tumour size was 2·5 (range 0·15–20·5) cm. Of the 51 NF-PNETs with a diameter of no more than 2 cm, 12 (24 per cent) were diagnosed as carcinoma. Overall 20 patients (16·0 per cent) had metastases to the lymph nodes. The minimum size of the tumour with lymph node metastasis was 1·2 cm. Having a NF-PNET of 2 cm or larger significantly increased the probability of a poorly differentiated carcinoma (P = 0·006), and having a NF-PNET of at least 2·5 cm significantly increased the probability of lymph node metastasis (P = 0·048). The 5-year cumulative survival rate after curative resection was 89·7 per cent. During a median follow-up of 31·5 months, there were 27 recurrences (23·1 per cent) and 13 disease-specific deaths (11·1 per cent) among the 117 patients who had an R0 resection. All patients who underwent repeat operations were alive without additional recurrence after a mean(s.d.) follow-up of 27·1(18·0) months.

Conclusion

Curative surgery should be performed for control of primary NF-PNETs. Lymph node dissection for NF-PNETs of 2·5 cm or larger and at least node sampling for tumours with a diameter of 1 cm or more are recommended. Debulking surgery should be considered for advanced tumours.
External biliary drainage and liver regeneration after major hepatectomy
Authors: Otao R , Beppu T , Isiko T , Mima K , Okabe H , Hayashi H , Masuda T , Chikamoto A , Takamori H , Baba H
Published: October 2012

Background

Bile acid signalling and farnesoid X receptor activation are assumed to be essential for liver regeneration. This study was designed to investigate the association between serum bile acid levels and extent of liver regeneration after major hepatectomy.

Methods

Patients who underwent left- or right-sided hemihepatectomy between 2006 and 2009 at the authors' institution were eligible for inclusion. Patients were divided into two groups: those undergoing hemihepatectomy with external bile drainage by cystic duct tube (group 1) and those having hemihepatectomy without drainage (group 2). Serum bile acid levels were measured before and after hepatectomy. Computed tomography was used to calculate liver volume before hepatectomy and remnant liver volume on day 7 after surgery.

Results

A total of 46 patients were enrolled. Mean(s.d.) serum bile acid levels on day 3 after hemihepatectomy were significantly higher in group 2 than in group 1 (11·6(13·5) versus 2·7(2·1) µmol/l; P = 0·003). Regenerated liver volumes on day 7 after hepatectomy were significantly greater in group 2 138·1(135·9) ml versus 40·0(158·8) ml in group 1; P = 0·038). Liver regeneration volumes and rates on day 7 after hemihepatectomy were positively associated with serum bile acid levels on day 3 after hemihepatectomy (P = 0·006 and P < 0·001 respectively). The incidence of bile leakage was similar in the two groups.

Conclusion

Initial liver regeneration after major hepatectomy was less after biliary drainage and was associated with serum bile acid levels. External biliary drainage should be used judiciously after liver resection.
KRAS status and outcome of liver resection after neoadjuvant chemotherapy including bevacizumab
Authors: Stremitzer S , Stift J , Gruenberger B , Tamandl D , Aschacher T , Wolf B , Wrba F , Gruenberger T
Published: October 2012

Background

The prognostic value of KRAS mutation in patients with colorectal cancer liver metastases (CLM) receiving neoadjuvant chemotherapy including bevacizumab before liver resection is unclear.

Methods

The KRAS and BRAF status of resected CLM was assessed in prospectively studied patients. Mutations were correlated with recurrence-free and overall survival. Only patients with remaining vital tumour cells in the resected specimen and those without disease progression were analysed; those with progressive disease did not undergo resection.

Results

A total of 60 patients were enrolled. Fifteen (25 per cent) had a KRAS mutation, but none of the 60 patients had a BRAF mutation. The radiological response to neoadjuvant chemotherapy including bevacizumab, assessed according to the Response Evaluation Criteria In Solid Tumours, was partial in 52 patients (87 per cent) and the remaining eight had stable disease. The partial response rate was similar in patients with a KRAS mutation and those with the wild-type gene (12 of 15 versus 40 of 45 patients; P = 0·400). KRAS mutation had a negative prognostic effect on recurrence-free survival (hazard ratio (HR) 2·48, 95 per cent confidence interval 1·26 to 4·89; P = 0·009) and overall survival (HR 3·51, 1·30 to 9·45; P = 0·013).

Conclusion

This study provided further evidence for the prognostic importance of KRAS status in terms of recurrence-free and overall survival. Neoadjuvant chemotherapy including bevacizumab elicited a response, irrespective of KRAS status, in this selected group of patients with CLM.
Effects of hybrid minimally invasive oesophagectomy on major postoperative pulmonary complications8
Authors: Briez N , Piessen G , Torres F , Lebuffe G , Triboulet J-P , Mariette C
Published: October 2012

Background

Morbidity after oesophageal cancer surgery remains high, mainly due to major postoperative pulmonary complications (MPPCs). The aim of this study was to test the hypothesis that hybrid minimally invasive oesophagectomy (HMIO) decreases the 30-day MPPC rate without compromising oncological outcomes.

Methods

Consecutive patients undergoing curative oesophagectomy for cancer by laparoscopic gastric mobilization and open thoracotomy (HMIO) between January 2004 and December 2009 were matched to randomly selected patients undergoing a totally open approach during the same study interval. Matching variables were age, sex, cancer stage, location of the primary tumour, histological subtype, American Society of Anesthesiologists grade, malnutrition, neoadjuvant chemoradiation and epidural analgesia.

Results

MPPCs at 30 days were significantly less frequent after HMIO compared with open surgery (15·7 versus 42·9 per cent; P < 0·001). Postoperative in-hospital mortality and overall morbidity rates were 4·3 and 47·5 per cent respectively, again significantly lower in the HMIO group: 1·4 versus 7·1 per cent (P = 0·018) and 35·7 versus 59·3 per cent (P < 0·001). In multivariable analysis, HMIO, adenocarcinoma subtype, epidural analgesia and surgery after 2006 were independent protective factors against MPPCs, and HMIO was independently protective against acute respiratory distress syndrome (ARDS). Lymph node yields and survival were similar in the two groups.

Conclusion

HMIO for oesophageal cancer, using laparoscopic gastric mobilization and open right thoracotomy, offered a substantial and independent protective effect against MPPCs, including ARDS, without compromising oncological outcomes.
Author's reply: Comparison of 30-day, 90-day and in-hospital postoperative mortality for eight different cancer types (Br J Surg 2012; 99: 1149–1154)
Authors: Damhuis R A M
Published: October 2012

No
Liquid chromatography and mass spectrometry of haem biosynthetic intermediates: a review
Authors: Benton Christopher M. , Lim Chang Kee
Published: October 2012

This article discusses the separation, analysis and characterisation of intermediates and oxidative by‐products of the haem biosynthetic pathway by liquid chromatography and mass spectrometry. Techniques reviewed include high‐performance liquid chromatography, ultra‐high‐performance liquid chromatography, capillary electrophoresis, ion mobility spectrometry, mass spectrometry and tandem mass spectrometry. The emphasis was on the analysis of biological and clinical samples. Copyright © 2012 John Wiley & Sons, Ltd.
Two critical periods in early visual cortex during figure–ground segregation
Authors: Wokke Martijn E. , Sligte Ilja G. , Steven Scholte H. , Lamme Victor A. F.
Published: October 2012

The ability to distinguish a figure from its background is crucial for visual perception. To date, it remains unresolved where and how in the visual system different stages of figure–ground segregation emerge. Neural correlates of figure border detection have consistently been found in early visual cortex (V1/V2). However, areas V1/V2 have also been frequently associated with later stages of figure–ground segregation (such as border ownership or surface segregation). To causally link activity in early visual cortex to different stages of figure–ground segregation, we briefly disrupted activity in areas V1/V2 at various moments in time using transcranial magnetic stimulation (TMS). Prior to stimulation we presented stimuli that made it possible to differentiate between figure border detection and surface segregation. We concurrently recorded electroencephalographic (EEG) signals to examine how neural correlates of figure–ground segregation were affected by TMS. Results show that disruption of V1/V2 in an early time window (96–119 msec) affected detection of figure stimuli and affected neural correlates of figure border detection, border ownership, and surface segregation. TMS applied in a relatively late time window (236–259 msec) selectively deteriorated performance associated with surface segregation. We conclude that areas V1/V2 are not only essential in an early stage of figure–ground segregation when figure borders are detected, but subsequently causally contribute to more sophisticated stages of figure–ground segregation such as surface segregation.
Characterization of the weak calcium binding of trimeric globular adiponectin
Authors: Yu Dongmei , Zhang Chao , Wang Han , Qin Peiwu
Published: October 2012

Adiponectin is secreted from adipose tissue and functions as a protein hormone in regulating glucose metabolism and fatty acid catabolism. Adiponectin plays an important role as a novel risk factor and potential diagnostic and prognostic biomarker in cancer. Crystal structures of globular adiponectin have been resolved with three calcium‐binding sites on the top of its central tunnel. However, the calcium‐binding property of adiponectin remains elusive. Mouse globular adiponectin was cloned into pET11a and expressed in Escherichia coli. The folding of adiponectin was indicated by the spread of resonances in HSQC spectrum. Luminescence resonance energy transfer was used to obtain the binding constant (Kd) of Tb3+ and the inhibitor constant (Ki) of Ca2+ for globular adiponectin. The obtained calcium‐binding affinity to adiponectin is relatively low (~2 mM), which indicates that the high concentration of adiponectin in circulating system may function as calcium storage bank and buffer the free calcium concentration. Copyright © 2012 John Wiley & Sons, Ltd.
Targeted proteomic dissection of Toxoplasma cytoskeleton sub‐compartments using MORN1
Authors: Lorestani Alexander , Ivey F. Douglas , Thirugnanam Sivasakthivel , Busby Michele A. , Marth Gabor T. , Cheeseman Iain M. , Gubbels Marc‐Jan
Published: October 2012

The basal complex in Toxoplasma functions as the contractile ring in the cell division process. Basal complex contraction tapers the daughter cytoskeleton toward the basal end and is required for daughter segregation. We have previously shown that the protein MORN1 is essential for basal complex assembly and likely acts as a scaffolding protein. To further our understanding of the basal complex, we combined subcellular fractionation with an affinity purification of the MORN1 complex and identified its protein composition. We identified two new components of the basal complex, one of which uniquely associated with the basal complex in mature parasites, the first of its kind. In addition, we identified several other novel cytoskeleton proteins with different spatiotemporal dynamics throughout cell division. Since many of these proteins are unique to Apicomplexa this study significantly contributes to the annotation of their unique cytoskeleton. Furthermore, we show that G‐actin binding protein TgCAP is localized at the apical cap region in intracellular parasites, but quickly redistributes to a cytoplasmic localization pattern upon egress. © 2012 Wiley Periodicals, Inc.
Polar expansion during cytokinesis
Authors: Gudejko Heather F.M. , Alford Lea M. , Burgess David R.
Published: October 2012

Vesicle trafficking and new membrane addition at the cleavage furrow have been extensively documented. However, less clear is the old idea that expansion at the cell poles occurs during cytokinesis. We find that new membrane is added to the cell poles during anaphase, causing the plasma membrane to expand coincident with the constriction of the contractile ring and may provide a pushing force for membrane ingression at the furrow. This membrane addition occurs earlier during mitosis than membrane addition at the furrow and is dependent on actin and astral microtubules. The membrane that is added at the polar regions is compositionally distinct from the original cell membrane in that it is devoid of GM1, a component of lipid rafts. These findings suggest that the growth of the plasma membrane at the cell poles during cell division is not due to stretching as previously thought, but due to the addition of compositionally unique new membrane. © 2012 Wiley Periodicals, Inc
Quantification of MAP and molecular motor activities on geometrically controlled microtubule networks
Authors: Portran Didier , Gaillard Jeremie , Vantard Marylin , Thery Manuel
Published: October 2012

The spatial organization of the microtubule (MT) network directs cell polarity and mitosis. It is finely regulated by hundreds of different types of microtubule‐associated proteins and molecular motors whose specific functions are difficult to investigate directly in cells. Here, we have investigated their functions using geometrically controlled MT networks in vitro in cell‐free assay. This was achieved by developing a new method to spatially define MT nucleation using MT microseeds adsorbed on a micropatterned glass substrate. This method could be used to control MT growth and the induction of complex MT networks. We selected the interaction of two radial arrays of dynamic and polarized MTs to analyze the formation of the central antiparallel MT bundle. We investigated the effects of the MT cross‐linker anaphase spindle elongation 1 (Ase1) and the kinesin motor Klp2, which are known to regulate MT organization in the spindle midzone. We thus identified the respective roles of each protein and revealed their synergy on the establishment of stable antiparallel MT bundles by quantifying MT interactions over hundreds of comparable MT networks. © 2012 Wiley Periodicals, Inc
A critical reevaluation of the stationary axonal cytoskeleton hypothesis
Authors: Brown Anthony , Jung Peter
Published: October 2012

Neurofilaments are transported along axons in a rapid intermittent and bidirectional manner but there is a long‐standing controversy about whether this applies to all axonal neurofilaments. Some have proposed that only a small proportion of axonal neurofilaments are mobile and that most are deposited into a persistently stationary and extensively cross‐linked cytoskeleton that remains fixed in place for many months without movement, turning over very slowly. In contrast, others have proposed that this hypothesis is based on a misinterpretation of the experimental data and that, in fact, all axonal neurofilaments move. These contrary perspectives have distinct implications for our understanding of how neurofilaments are organized and reorganized in axons both in health and disease. Here, we discuss the history and substance of this controversy. We show that the published data on the kinetics and distribution of neurofilaments along axons favor a simple “stop and go” transport model in which axons contain a single population of neurofilaments that all move in a stochastic, bidirectional and intermittent manner. Based on these considerations, we propose a dynamic view of the neuronal cytoskeleton in which all neurofilaments cycle repeatedly between moving and pausing states throughout their journey along the axon. The filaments move infrequently, but the average pause duration is on the order of hours rather than weeks or months. Against this fluid backdrop, the action of molecular motors on neurofilaments can have dramatic effects on neurofilament organization that would not be possible if the neurofilaments were extensively cross‐linked into a truly stationary network. © 2012 Wiley Periodicals, Inc
CD66c is a novel marker for colorectal cancer stem cell isolation, and its silencing halts tumor growth in vivo
Authors: Gemei Marica , Mirabelli Peppino , Di Noto Rosa , Corbo Claudia , Iaccarino Antonino , Zamboli Anna , Troncone Giancarlo , Galizia Gennaro , Lieto Eva , Del Vecchio Luigi , Salvatore Francesco
Published: October 2012

BACKGROUND:

Despite the well recognized expression of the cell surface markers cluster of differentiation 44 (homing cell adhesion molecule) and CD133 (Prominin 1) on human colorectal cancer stem cells (CCSCs), these molecules do not appear to be effective targets for stem cell‐directed therapies. Because the surface marker CD66c (also known as carcinoembryonic antigen‐related cell adhesion molecule 6) has demonstrated promise as a therapeutic target in pancreatic malignancy, the authors evaluated its potential as a target for stem cell‐directed treatment of colorectal cancer.

METHODS:

First, the authors characterized CD66c expression by flow cytometry and immunohistochemistry in colon cancer samples and in normal colon tissues. Then, the coexpression of CD66c and CD133 was evaluated on putative CCSCs. CD66c expression also was measured in stem cell‐enriched colon spheres. Finally, the effects of small‐interfering RNA‐mediated CD66c silencing on the in vitro and in vivo growth of Caco2 colon cancer cells were evaluated.

RESULTS:

CD66c expression was significantly higher in colon cancers than in contiguous normal colon tissues and paralleled cancer stage. CD66c was absent in CD133‐positive cells that were isolated from normal colon, whereas its expression was brightest (CD66cbright) in CD133‐positive cells from colon cancer samples. In vitro experiments demonstrated that colon spheres were considerably enriched in a CD66cbright population in a fashion comparable to the enrichment observed in fresh liver metastases. In vitro proliferation and clonogenic potential were hampered when CD66c was silenced in Caco2 cells. Finally, in vivo xenograft experiments demonstrated that CD66c silencing almost completely abrogated the tumorigenic potential of Caco2 cells.

CONCLUSIONS:

CD66cbright expression was associated with colon cancer stem cells and CD66c silencing blocked tumor growth, thereby opening the way to a potential new treatment for colon cancer. Cancer 2013. © 2012 American Cancer Society.
Patient‐specific finite element analysis of carotid artery stenting: a focus on vessel modeling
Authors: Auricchio F. , Conti M. , Ferrara A. , Morganti S. , Reali A.
Published: October 2012

Finite element analysis is nowadays a well‐assessed technique to investigate the impact of stenting on vessel wall and, given the rapid progression of both medical imaging techniques and computational methods, the challenge of using the simulation of carotid artery stenting as procedure planning tool to support the clinical practice can be approached. Within this context, the present study investigates the impact of carotid stent apposition on carotid artery anatomy by means of patient‐specific finite element analysis. In particular, we focus on the influence of the vessel constitutive model on the prediction of carotid artery wall tensional state of lumen gain and of vessel straightening. For this purpose, we consider, for a given stent design and CA anatomy, two constitutive models for the CA wall, that is, a hyperelastic isotropic versus a fiber‐reinforced hyperelastic anisotropic model. Despite both models producing similar patterns with respect to stress distribution, the anisotropic model predicts a higher vessel straightening and a more evident discontinuity of the lumen area near the stent ends as observed in the clinical practice. Although still affected by several simplifications, the present study can be considered as further step toward a realistic simulation of carotid artery stenting.Copyright © 2012 John Wiley & Sons, Ltd.
Evaluation of FMH QuikQuant for the detection and quantification of fetomaternal hemorrhage
Authors: Pastoret Cedric , Priol Jerome Le , Fest Thierry , Roussel Mikael
Published: October 2012

Background:

The Kleihauer–Betke test (KBT) is the most widely used assay for fetomaternal hemorrhage (FMH) detection in rhesus D negative women. In the current study, we sought to evaluate the performance of a flow cytometry (FCM) kit (FMH QuikQuant) using an anti‐HbF antibody.

Methods:

Eighty‐three pregnant women, 58 umbilical cord blood (UCB) dilutions in adult blood, and 6 control samples were tested in parallel with FCM and KBT.

Results:

Firstly, we compared for each assay, on the 58 UCB preparations, results obtained to dilutions prepared. FCM results showed an excellent correlation (r = 0.97), a high reproducibility with a coefficient of variation lower than 20% for values reaching 10 fetal RBCs. KBT values were correlated (r = 0.94) but exhibited a poor reproducibility. Then, we compared both techniques on all samples. FCM showed a good correlation with KBT (r = 0.87) but the KBT exhibited a systematic overestimation of the FMH. For 8 out of 83 pregnant women, KBT was positive. Five were concordant with FCM results (KBT+/FCM+). On the three discordant (KBT+/FCM−), 2 were finally classified as false positive of the KBT because a second control sample was negative and additionally, FCM identified an increased rate of F cells. One discordant case (KBT+/FCM−) remained unexplained. By receiver operating characteristic analysis, we found a threshold at 4.5 RBCs for FCM with a sensitivity of 89.8% and a specificity of 93.2%.

Conclusions:

The FMH QuikQuant kit is a reliable and highly reproductive FCM method for FMH quantification. © 2012 International Clinical Cytometry Society
Digital rights management system with user privacy, usage transparency, and superdistribution support
Authors: Yen Chih‐Ta , Liaw Horng‐Twu , Lo Nai‐Wei
Published: October 2012

In the modern world, digital content has been massively produced, distributed, and consumed by human beings; consequently, how to protect the rights and benefits of content consumers, producers, and distributors has become a crucial issue. One promising solution is to design a full‐fledged digital rights management (DRM) system. In this study we introduce a new design on the digital rights management system providing user privacy, usage transparency, and superdistribution. A comprehensive set of DRM processing functions and corresponding mechanisms are developed in our system to support various business process requirements. Superdistribution support is embedded in our system design. A prototype is implemented to verify our system design. To protect consumer privacy, a temporary identity is generated for each consumer using the KryptoKnight protocol. Elliptic curve cryptography‐based encryption scheme is adopted for messages transmitted among servers and client over an unsecure communication channel. For usage transparency, a user‐friendly DRM client package (software) is introduced in the proposed DRM system to achieve content protection and support user convenience in usage.Copyright © 2012 John Wiley & Sons, Ltd.
Protocol design and data detection for two‐way relay networks with fractional asynchronous delays
Authors: Fang Zhaoxi , Liang Feng , Zhang Shaozhong , Shi Jiong
Published: October 2012

In wireless two‐way relay systems, it is difficult to achieve perfect timing synchronization among different nodes. In this paper, we investigate relaying protocol design and data detect schemes for asynchronous two‐way relaying systems to combat the intersymbol interference caused by asynchronous transmission. We consider fractional asynchronous delays and two schemes are proposed based on cyclic prefixed single carrier block transmission, namely, the receiver frequency domain equalization scheme and relay synchronization and network coding (RSNC) scheme. In the receiver frequency domain equalization scheme, the relay simply amplifies the received signal and forwards to the two source nodes, and fractionally spaced frequency domain equalizer (FS‐FDE) is employed at the receiver to recover the transmit data. In the RSNC scheme, the asynchronous signals are resynchronized with an FS‐FDE at the relay node. The output signals of FS‐FDE are then demodulated and network coded before forwarding to the two source nodes. In this RSNC scheme, data detection at the source nodes is the same as that in synchronous networks because the asynchronous signals have already been synchronized at the relay node. Simulation results show that the performance of both schemes is almost the same as in the perfect synchronized two‐way relaying systems. Copyright © 2012 John Wiley & Sons, Ltd.
Functional redundancy between Cdc14 phosphatases in zebrafish ciliogenesis
Authors: Clément Aurélie , Solnica‐Krezel Lilianna , Gould Kathleen L.
Published: October 2012

Background: Cyclin‐dependent kinases (Cdks) and their counteracting phosphatases are key regulators of cell cycle progression. In yeasts, the Cdc14 family of phosphatases promotes exit from mitosis and progression through cytokinesis by reversing phosphorylation of Cdk1 substrates. In vertebrates, CDC14 paralogs, CDC14A and CDC14B, have so far been implicated in processes ranging from DNA damage repair, meiosis, centrosome duplication to ciliogenesis. However, the question of whether CDC14 paralogs can functionally compensate for each other has yet to be addressed. Results: Here, using antisense morpholino oligonucleotides to inhibit Cdc14A1 function, we observed that Cdc14A1 depleted zebrafish embryos displayed ventrally curved body and left‐right asymmetry defects, similar to Cdc14B deficient embryos and zebrafish mutants with cilia defects. Accordingly, we found that Cdc14A1, like Cdc14B, plays a role in ciliogenesis in the Kupffer's vesicle (KV) and other ciliated tissues, and can do so independently of its function in cell cycle. Furthermore, we observed reciprocal suppression of KV cilia length defects of Cdc14A1 and Cdc14B deficient embryos by cdc14b and cdc14a1 RNAs, respectively. Conclusions: Together, these studies demonstrate for the first time that Cdc14A and Cdc14B have overlapping functions in the ciliogenesis process during zebrafish development. Developmental Dynamics, 2012. © 2012 Wiley Periodicals, Inc.
Genomic variation in cline shape across a hybrid zone
Authors: Kingston Sarah E. , Jernigan Robert W. , Fagan William F. , Braun David , Braun Michael J.
Published: October 2012

Hybrid zones are unique biological interfaces that reveal both population level and species level evolutionary processes. A genome‐scale approach to assess gene flow across hybrid zones is vital, and now possible. In Mexican towhees (genus Pipilo), several morphological hybrid gradients exist. We completed a genome survey across one such gradient (9 populations, 140 birds) using mitochondrial DNA, 28 isozyme, and 377 AFLP markers. To assess variation in introgression among loci, cline parameters (i.e., width, center) for the 61 clinally varying loci were estimated and compiled into genomic distributions for tests against three empirical models spanning the range of observed cline shape. No single model accounts for observed variation in cline shape among loci. Numerous backcross individuals near the gradient center confirm a hybrid origin for these populations, contrary to a previous hypothesis based on social mimicry and character displacement. In addition, the observed variation does not bin into well‐defined categories of locus types (e.g., neutral vs. highly selected). Our multi‐locus analysis reveals cross‐genomic variation in selective constraints on gene flow and locus‐specific flexibility in the permeability of the interspecies membrane.
Fine‐scale selection by ovipositing females increases egg survival
Authors: Gall Brian G. , Brodie Edmund D. , Brodie Edmund D.
Published: October 2012

One of the most important defenses for the eggs of ovipositing female organisms is to avoid being laid in the same habitat as their predators. However, for most organisms, completely avoiding an offspring's predators is not possible. One mechanism that has been largely overlooked is for females to partition an oviposition site into microhabitats that differ in quality for offspring survival. We conducted a series of experiments to examine whether female newts avoid microhabitats utilized by their offspring's primary predator, caddisfly larvae. Female newts avoided laying eggs near predatory caddisflies and shifted egg laying upward in the water column when provided with a vertical dimension. Caddisflies were attracted to chemical stimuli from female newts and their eggs, yet primarily used benthic areas in experimental chambers. Finally, results from a field experiment indicate that the behavioral strategy employed by female newts increases offspring survival. This subset of non‐genetic maternal effects, micro‐oviposition avoidance, is likely an important yet underexplored mechanism by which females increase offspring survival.
Photocatalytic TiO2 Macroscopic Fibers Obtained Through Integrative Chemistry
Authors: Kinadjian Natacha , Le Bechec Mickael , Pigot Thierry , Dufour Fabien , Durupthy Olivier , Bentaleb Ahmed , Prouzet Eric , Lacombe Sylvie , Backov Rénal
Published: October 2012

The photocatalytic properties of titanium dioxide depend not only on its electronic properties, but also on the material size and shape, which can increase interactions between the reactants and catalyst. Most studies to date show that reducing the particle size down to the nanoscale increases photocatalytic efficiency, as a result of a higher surface to volume ratio and because a larger proportion of the material is actually irradiated by light. We demonstrate that a multiscale shape design, which integrates surface roughness, particle shape, and 1D material processing and orientation, can favor photocatalytic properties in the solid–gas regime, especially mineralization (conversion into CO2), when the hierarchical 1D orientation of the material is combined with unidirectional gas flow. Several materials with hierarchical structure were prepared and characterized. They have been tested for the photocatalytic mineralization of gaseous acetone and compared with commercial catalysts. Our study reveals that a suitable combination of multiscale design and optimization of the material orientation and gas flow favors high mineralization.
Competing Symmetry Breaking and Spin Crossover in [FeH2L2–Me](ClO4)2
Authors: Watanabe Hiroshi , Bréfuel Nicolas , Collet Eric , Toupet Loïc , Tanaka Koichiro , Tuchagues Jean‐Pierre
Published: October 2012

In this contribution, we describe the symmetry breaking that appears in the low‐spin phase of the spin crossover (SC) complex [FeH2L2–Me](ClO4)2, [H2L2–Me = Bis{[(2‐methylimidazol‐4‐yl)methylidene]‐3‐aminopropyl}ethylenediamine], for which low‐spin (LS) to high‐spin (HS) transition may be thermally activated or photoinduced. In the LS phase stable at low temperature, a symmetry breaking occurs at around 120 K, while in the photoinduced HS (PIHS) state the high symmetry is recovered. The relaxation from this PIHS state to the LS low‐symmetry phase occurs through an intermediate LS high‐symmetry phase. The sequence of phases was evidenced by using magnetic susceptibility, X‐ray diffraction, and infrared spectroscopy data.
Early assessment of acute coronary syndromes in the emergency department: the potential diagnostic value of circulating microRNAs
Authors: Oerlemans Martinus I. F. J. , Mosterd Arend , Dekker Marieke S. , de Vrey Evelyn A. , van Mil Alain , Pasterkamp Gerard , Doevendans Pieter A. , Hoes Arno W. , Sluijter Joost P. G.
Published: October 2012

Previous studies investigating the role of circulating microRNAs in acute coronary syndrome (ACS) were based on small patient numbers, performed no comparison with established markers of cardiac injury and did not have appropriate controls. We determined the potential diagnostic value of circulating microRNAs as novel early biomarkers in 332 suspected ACS patients on presentation to the emergency department (ED) in a prospective single‐centre study including cardiac miRNAs (miR‐1, ‐208a and ‐499), miR‐21 and miR‐146a. Levels of all miRs studied were significantly increased in 106 patients diagnosed with ACS, even in patients with initially negative high‐sensitive (hs) troponin or symptom onset <3 h. MiR‐1, miR‐499 and miR‐21 significantly increased the diagnostic value in all suspected ACS patients when added to hs‐troponin T (AUC 0.90). These three miRs were strong predictors of ACS independent of clinical co‐variates including patient history and cardiovascular risk factors. Interestingly, the combination of these three miRs resulted in a significantly higher AUC of 0.94 than hs‐troponin T (0.89). Circulating microRNAs hold great potential as novel early biomarkers for the management of suspected ACS patients.
Quantifying effects of deep and near‐surface chemical erosion on cosmogenic nuclides in soils, saprolite, and sediment
Authors: Riebe Clifford S. , Granger Darryl E.
Published: October 2012

Cosmogenic nuclides in rock, soil, and sediment are routinely used to measure denudation rates of catchments and hillslopes. Although it has been shown that these measurements are prone to biases due to chemical erosion in regolith, most studies of cosmogenic nuclides have ignored this potential source of error. Here we quantify the extent to which overlooking effects of chemical erosion introduces bias in interpreting denudation rates from cosmogenic nuclides. We consider two end‐member effects: one due to weathering near the surface and the other due to weathering at depth. Near the surface, chemical erosion influences nuclide concentrations in host minerals by enriching (or depleting) them relative to other more (or less) soluble minerals. This increases (or decreases) their residence times relative to the regolith as a whole. At depth, where minerals are shielded from cosmic radiation, chemical erosion causes denudation without influencing cosmogenic nuclide buildup. If this effect is ignored, denudation rates inferred from cosmogenic nuclides will be too low. We derive a general expression, termed the ‘chemical erosion factor’, or CEF, which corrects for biases introduced by both deep and near‐surface chemical erosion in regolith. The CEF differs from the ‘quartz enrichment factor’ of previous work in that it can also be applied to relatively soluble minerals, such as olivine. Using data from diverse climatic settings, we calculate CEFs ranging from 1.03 to 1.87 for cosmogenic nuclides in quartz. This implies that ignoring chemical erosion can lead to errors of close to 100% in intensely weathered regolith. CEF is strongly correlated with mean annual precipitation across our sites, reflecting climatic influence on chemical weathering. Our results indicate that quantifying CEFs is crucial in cosmogenic nuclide studies of landscapes where chemical erosion accounts for a significant fraction of the overall denudation. Copyright © 2012 John Wiley & Sons, Ltd.
Control of hydrothermal waves in a thermocapillary flow using a gradient‐based control strategy
Authors: Muldoon Frank
Published: October 2012

The problem of controlling the hydrothermal waves in a thermocapillary flow is addressed using a gradient‐based control strategy. The state equations are the two‐dimensional unsteady incompressible Navier–Stokes and energy equations under the Boussinesq approximation. The modeled problem is the ‘open boat’ process of crystal growth, the flow which is driven by Marangoni and buoyancy effects. The control is a spatially and temporally varying heat flux boundary condition at the free surface. The control that minimizes the hydrothermal waves is found using a conjugate gradient method, where the gradient of the objective function with respect to the control variables is obtained from solving a set of adjoint equations. The effectiveness of choices of the parameters governing the control algorithm is examined. Almost complete suppression of the hydrothermal waves is obtained for certain choices of the parameters governing the control algorithm. The numerical issues involved with finding the control using the optimizer are discussed, and the features of the resulting control are analyzed with the goal of understanding how it affects the flow.Copyright © 2012 John Wiley & Sons, Ltd.
Landscape of somatic allelic imbalances and copy number alterations in human lung carcinoma
Authors: Staaf Johan , Isaksson Sofi , Karlsson Anna , Jönsson Mats , Johansson Leif , Jönsson Per , Botling Johan , Micke Patrick , Baldetorp Bo , Planck Maria
Published: October 2012

Lung cancer is the worldwide leading cause of death from cancer and has been shown to be a heterogeneous disease at the genomic level. To delineate the genomic landscape of copy number alterations, amplifications, loss‐of‐heterozygosity (LOH), tumor ploidy and copy‐neutral allelic imbalance in lung cancer, microarray‐based genomic profiles from 2,141 tumors and cell lines including adenocarcinomas (AC, n = 1,206), squamous cell carcinomas (SqCC, n = 467), large cell carcinomas (n = 37) and small cell lung carcinomas (SCLC, n = 88) were assembled from different repositories. Copy number alteration differences between lung cancer histologies were confirmed in 285 unrelated tumors analyzed by BAC array comparative genomic hybridization. Tumor ploidy patterns were validated by DNA flow cytometry analysis of 129 unrelated cases. Eighty‐nine recurrent copy number alterations (55 gains, 34 losses) were identified harboring genes with gene expression putatively driven by gene dosage through integration with gene expression data for 496 cases. Thirteen and 26 of identified regions discriminated AC/SqCC and AC/SqCC/SCLC, respectively, while 48 regions harbored recurrent (n > 15) high‐level amplifications comprising established and putative oncogenes, differing in frequency and coamplification patterns between histologies. Lung cancer histologies displayed differences in patterns/frequency of copy number alterations, genomic architecture, LOH, copy‐neutral allelic imbalance and tumor ploidy, with AC generally displaying less copy number alterations and allelic imbalance. Moreover, a strong association was demonstrated between different types of copy number alterations and allelic imbalances with tumor aneuploidy. In summary, these analyses provide a comprehensive overview of the landscape of genomic alterations in lung cancer, highlighting differences but also similarities between subgroups of the disease.
CEBP factors regulate telomerase reverse transcriptase promoter activity in whey acidic protein‐T mice during mammary carcinogenesis
Authors: Kumar Mukesh , Witt Britta , Knippschild Uwe , Koch Sylvia , Meena Jitendra K. , Heinlein Christina , Weise Julia M. , Krepulat Frauke , Kuchenbauer Florian , Iben Sebastian , Rudolph Karl‐Lenhard , Deppert Wolfgang , Günes Cagatay
Published: October 2012

Telomerase is activated in the majority of invasive breast cancers, but the time point of telomerase activation during mammary carcinogenesis is not clear. We have recently presented a transgenic mouse model to study human telomerase reverse transcriptase (TERT) gene expression in vivo (hTERTp‐lacZ). In the present study, hTERTp‐lacZxWAP‐T bitransgenic mice were generated to analyze the mechanisms responsible for human and mouse TERT upregulation during tumor progression in vivo. We found that telomerase activity and TERT expression were consistently upregulated in SV40‐induced invasive mammary tumors compared to normal and hyperplastic tissues and ductal carcinoma in situ (DCIS). Human and mouse TERT genes are regulated similarly in the breast tissue, involving the CEBP transcription factors. Loss of CEBP‐α and induction of CEBP‐β expression correlated well with the activation of TERT expression in mouse mammary tumors. Transfection of CEBP‐α into human or murine cells resulted in TERT repression, whereas knockdown of CEBP‐α in primary human mammary epithelial cells resulted in reactivation of endogenous TERT expression and telomerase activity. Conversely, ectopic expression of CEBP‐β activated endogenous TERT gene expression. Moreover, ChIP and EMSA experiments revealed binding of CEBP‐α and CEBP‐β to human TERT‐promoter. This is the first evidence indicating that CEBP‐α and CEBP‐β are involved in TERT gene regulation during carcinogenesis.
Phosphorylated tubulin adaptor protein CRMP‐2 as prognostic marker and candidate therapeutic target for NSCLC
Authors: Oliemuller Erik , Peláez Rafael , Garasa Saray , Pajares María J. , Agorreta Jackeline , Pío Rubén , Montuenga Luis M. , Teijeira Alvaro , Llanos Susana , Rouzaut Ana
Published: October 2012

Collapsin response mediator protein‐2 (CRMP‐2) is the first described and most studied member of a family of proteins that mediate the addition of tubulin dimers to the growing microtubule. CRMPs have mainly been studied in the nervous system, but recently, they have been described in other tissues where they participate in vesicle transport, migration and mitosis. In this work, we aimed at studying the role of CRMP‐2 in lung cancer cell division. We first explored the expression of CRMP‐2 and phosphorylated (Thr 514) CRMP‐2 in 91 samples obtained from patients with localized nonsmall cell lung cancer. We observed a significant correlation between high levels of nuclear phosphorylated CRMP‐2 and poor prognosis in those patients. Interestingly, this association was only positive for untreated patients. To provide a mechanistic explanation to these findings, we used in vitro models to analyze the role of CRMP‐2 and its phosphorylated forms in cell division. Thus, we observed by confocal microscopy and immunoprecipitation assays that CRMP‐2 differentially colocalizes with the mitotic spindle during cell division. The use of phosphodefective or phosphomimetic mutants of CRMP‐2 allowed us to prove that anomalies in the phosphorylation status of CRMP‐2 result in changes in the mitotic tempo, and increments in the number of multinucleated cells. Finally, here we demonstrate that CRMP‐2 phosphorylation impairment, or silencing induces p53 expression and promotes apoptosis through caspase 3 activation. These results pointed to CRMP‐2 phosphorylation as a prognostic marker and potential new target to be explored in cancer therapy.
B4GALT1 gene knockdown inhibits the hedgehog pathway and reverses multidrug resistance in the human leukemia K562/adriamycin‐resistant cell line
Authors: Zhou Huimin , Zhang Zhaohai , Liu Chunqing , Jin Changgong , Zhang Jianing , Miao Xiaoyan , Jia Li
Published: October 2012

B4GALT1 gene encodes type II membrane‐bound glycoprotein, named β‐1, 4‐galactosyltransferase 1 (β1, 4‐Gal‐T1), which can transfer galactose to acceptor sugars. B4GALT1 gene plays important roles in physiological process and disease development. In this study, we investigate the possible role and mechanism of B4GALT1 gene in multidrug resistance of human leukemia cell line. Significantly, higher expression of B4GALT1 was observed in adriamycin‐resistant (ADR) K562 cell line (K562/ADR) than that in K562 cell line by real‐time polymerase chain reaction and Western blotting. The activity of β1, 4‐Gal‐T1 enzyme, and Galβ‐1,4GlcNAc structures on cell membrane glycoproteins was found at higher levels in K562/ADR cells than those in K562 cells. Further analysis of the B4GALT1 deregulation after using RNA interference approach showed that the silencing of B4GALT1 in K562/ADR cells resulted in increased sensitivity to chemotherapeutic drugs both in vitro and in vivo. The activity of the hedgehog signaling pathway affected the chemosensitivity of K562/ADR cells and was downregulated in K562/ADR cells with suppression of B4GALT1 gene. We hypothesize that B4GALT1 is responsible for the overcoming multidrug resistance in human leukemia therapy via regulating the activity of the hedgehog signaling pathway. © 2012 IUBMB, IUBMB Life, 64(11): 889–900, 2012
Role of androgen receptor polyQ chain elongation in Kennedy's disease and use of natural osmolytes as potential therapeutic targets
Authors: Kumar Raj
Published: October 2012

Instability of CAG triplet repeat encoding polyglutamine (polyQ) stretches in the gene for target protein has been implicated as a putative mechanism in several inherited neurodegenerative diseases. Expansion of polyQ chain length in the androgen receptor (AR) causes spinal and bulbar muscular atrophy (SBMA) or Kennedy's disease. Although the mechanisms underlying gain‐of‐neurotoxic function are not completely understood, suggested pathological mechanisms of SBMA involve the formation of AR nuclear and cytoplasmic aggregates, a characteristic feature of patients with SBMA. The fact that certain AR coactivators are sequestered into the nuclear inclusions in SBMA possibly through protein–protein interactions supports the notion that AR transcriptional dysregulation may be a potential pathological mechanism leading to SBMA. AR conformational states associated with aberrant polyQ tract also modulate the interaction of AR with several coactivators. In many cases, such diseases can be treated through protein replacement therapy; however, because recombinant proteins do not cross the blood–brain barrier, the effectiveness of such therapies is limited in case of neurodegenerative diseases that warrant alternative therapeutic approaches. Among different approaches, inhibiting protein aggregation with small molecules that can stimulate protein folding and reverse aggregation are the most promising ones. Thus, naturally occurring osmolytes or “chemical chaperones” that can easily cross the blood–brain barrier and stabilize the functional form of a mutated protein by shifting the folding equilibrium away from degradation and/or aggregation is a useful therapeutic approach. In this review, we discuss the role of polyQ chain length extension in the pathophysiology of SBMA and the use of osmolytes as potential therapeutic tool. © 2012 IUBMB, IUBMB Life, 64(11): 879–884, 2012
3.3: High‐Speed Shift‐Register for High Resolution AMD with Self‐aligned Coplanar a‐IGZO TFTs
Authors: Geng Di , Kang Dong Han , Seok Man Ju , Mativenga Mallory , Jang Jin
Published: October 2012

We report a high speed shift register (SR) for high resolution AMD using self‐aligned coplanar amorphous‐indium‐gallium‐zinc‐oxide (a‐IGZO) thin‐film transistors (TFTs). The SR could operate with clock frequency of 500 kHz without any distortion and ripple at a supply voltage (VDD) of 15 V, which confirm the use of a‐IGZO TFT shift registers for high‐speed and high resolution AMD.
3.4L: Late‐News Paper: Physical Model and Simulation Platform for High‐Level Instability‐Aware Design of Amorphous Oxide Semiconductor Thin‐Film Transistors
Authors: Kim Dae Hwan , Kim Woojoon , Kim Yongsik , Hur Inseok , Bae Minkyung , Kong Dongsik , Jeong Hyun Kwang , Kim Dong Myong , Du Ahn Byung , Kim Gun Hee , Lee Je‐Hun , Nahm Ho‐Hyun , Kim Yong‐Sung
Published: October 2012

The negative bias illumination stress (NBIS)‐induced VT instability of amorphous InGaZnO thin‐film transistors (TFTs) is quantitatively investigated and a shallow donor state‐creation model is proposed as a physical mechanism. Furthermore, the difference between InGaZnO and HfInZnO TFTs in perspective of NBIS‐induced instability is consistently elucidated. We expect that the proposed model and simulation platform are potentially powerful tools for high‐level instability‐aware design of oxide TFT devices and circuits.