bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancement of lung tumorigenesis in a Gprc5a Knockout mouse by chronic extrinsic airway inflammation
Authors: Barta Peter , Van Pelt Carolyn , Men Taoyan , Dickey Burton F , Lotan Reuben , Moghaddam Seyed Javad 
Published: January 2012

Abstract

Background
Although cigarette smoking is the principal cause of lung carcinogenesis, chronic obstructive pulmonary disease (COPD), an inflammatory disease of the lung, has been identified as an independent risk factor for lung cancer. Bacterial colonization, particularly with non-typeable Haemophilus influenzae (NTHi), has been implicated as a cause of airway inflammation in COPD besides cigarette smoke. Accordingly, we hypothesized that lung cancer promotion may occur in a chronic inflammatory environment in the absence of concurrent carcinogen exposure.

Results
Herein, we investigated the effects of bacterial-induced COPD-like inflammation and tobacco carcinogen-enhanced tumorigenesis/inflammation in the retinoic acid inducible G protein coupled receptor knock out mouse model (Gprc5a-/- mouse) characterized by late-onset, low multiplicity tumor formation. Three-month-old Gprc5a-/- mice received 4 intraperitoneal injections of the tobacco-specific carcinogen, NNK, followed by weekly exposure to aerosolized NTHi lysate for 6 months. The numbers of inflammatory cells in the lungs and levels of several inflammatory mediators were increased in Gprc5a-/- mice treated with NTHi alone, and even more so in mice pretreated with NNK followed by NTHi. The incidence of spontaneous lung lesions in the Gprc5a-/- mice was low, but NTHi exposure led to enhanced development of hyperplastic lesions. Gprc5a-/- mice exposed to NNK alone developed multiple lung tumors, while NTHi exposure increased the number of hyperplastic foci 6-fold and the tumor multiplicity 2-fold. This was associated with increased microvessel density and HIF-1α expression.

Conclusion
We conclude that chronic extrinsic lung inflammation induced by bacteria alone or in combination with NNK enhances lung tumorigenesis in Gprc5a-/- mice.
Global gene expression changes in human embryonic lung fibroblasts induced by organic extracts from respirable air particles
Authors: Líbalová Helena , Uhlířová Kateřina , Kléma Jiří , Machala Miroslav , Šrám Radim J , Ciganek Miroslav , Topinka Jan 
Published: January 2012

Abstract

Background
Recently, we used cell-free assays to demonstrate the toxic effects of complex mixtures of organic extracts from urban air particles (PM2.5) collected in four localities of the Czech Republic (Ostrava-Bartovice, Ostrava-Poruba, Karvina and Trebon) which differed in the extent and sources of air pollution. To obtain further insight into the biological mechanisms of action of the extractable organic matter (EOM) from ambient air particles, human embryonic lung fibroblasts (HEL12469) were treated with the same four EOMs to assess changes in the genome-wide expression profiles compared to DMSO treated controls.

Method
For this purpose, HEL cells were incubated with subtoxic EOM concentrations of 10, 30, and 60 μg EOM/ml for 24 hours and global gene expression changes were analyzed using human whole genome microarrays (Illumina). The expression of selected genes was verified by quantitative real-time PCR.

Results
Dose-dependent increases in the number of significantly deregulated transcripts as well as dose-response relationships in the levels of individual transcripts were observed. The transcriptomic data did not differ substantially between the localities, suggesting that the air pollution originating mainly from various sources may have similar biological effects. This was further confirmed by the analysis of deregulated pathways and by identification of the most contributing gene modulations. The number of significantly deregulated KEGG pathways, as identified by Goeman's global test, varied, depending on the locality, between 12 to 29. The Metabolism of xenobiotics by cytochrome P450 exhibited the strongest upregulation in all 4 localities and CYP1B1 had a major contribution to the upregulation of this pathway. Other important deregulated pathways in all 4 localities were ABC transporters (involved in the translocation of exogenous and endogenous metabolites across membranes and DNA repair), the Wnt and TGF-β signaling pathways (associated particularly with tumor promotion and progression), Steroid hormone biosynthesis (involved in the endocrine-disrupting activity of chemicals), and Glycerolipid metabolism (pathways involving the lipids with a glycerol backbone including lipid signaling molecules).

Conclusion
The microarray data suggested a prominent role of activation of aryl hydrocarbon receptor-dependent gene expression.
Xylan oligosaccharides and cellobiohydrolase I (TrCel7A) interaction and effect on activity
Authors: Baumann Martin J , Borch Kim , Westh Peter 
Published: January 2012

Abstract

Background
The well-studied cellulase mixture secreted by Trichoderma reesei (anamorph to Hypocrea jecorina) contains two cellobiohydolases (CBHs), cellobiohydrolase I (TrCel7A) and cellobiohydrolase II (TrCeI6A), that are core enzymes for the solubilisation of cellulose. This has attracted significant research interest because of the role of the CBHs in the conversion of biomass to fermentable sugars. However, the CHBs are notoriously slow and susceptible to inhibition, which presents a challenge for the commercial utilisation of biomass. The xylans and xylan fragments that are also present in the biomass have been suggested repeatedly as one cause of the reduced activity of CHBs. Yet, the extent and mechanisms of this inhibition remain poorly elucidated. Therefore, we studied xylan oligosaccharides (XOSs) of variable lengths with respect to their binding and inhibition of both TrCel7A and an enzyme variant without the cellulose-binding domain (CBM).

Results
We studied the binding of XOSs to TrCel7A by isothermal titration calorimetry. We found that XOSs bind to TrCel7A and that the affinity increases commensurate with XOS length. The CBM, on the other hand, did not affect the affinity significantly, which suggests that XOSs may bind to the active site. Activity assays of TrCel7A clearly demonstrated the negative effect of the presence of XOSs on the turnover number.

Conclusions
On the basis of these binding data and a comparison of XOS inhibition of the activity of the two enzyme variants towards, respectively, soluble and insoluble substrates, we propose a competitive mechanism for XOS inhibition of TrCel7A with phosphoric swollen cellulose as a substrate.
Knockdown of menin affects pre-mRNA processing and promoter fidelity at the interferon-gamma inducible IRF1 gene
Authors: Auriemma Lauren B , Shah Shaili , Linden Lara M , Henriksen Melissa A 
Published: January 2012

Abstract

Background
The tumor suppressor menin (MEN1) is mutated in the inherited disease multiple endocrine neoplasia type I, and has several documented cellular roles, including the activation and repression of transcription effected by several transcription factors. As an activator, MEN1 is a component of the Set1-like mixed lineage leukemia (MLL) MLL1/MLL2 methyltransferase complex that methylates histone H3 lysine 4 (H3K4). MEN1 is localized to the signal transducer and activator of transcription 1 (STAT1)-dependent gene, interferon regulatory factor 1 (IRF1), and is further recruited when IRF1 transcription is triggered by interferon-γ signaling.

Results
RNAi-mediated knockdown of MEN1 alters the H3K4 dimethylation and H3 acetylation profiles, and the localization of histone deacetylase 3, at IRF1. While MEN1 knockdown does not impact the rate of transcription, IRF1 heteronuclear transcripts become enriched in MEN1-depleted cells. The processed mRNA and translated protein product are concomitantly reduced, and the antiviral state is attenuated. Additionally, the transcription start site at the IRF1 promoter is disrupted in the MEN1-depleted cells. The H3K4 demethylase, lysine specific demethylase 1, is also associated with IRF1, and its inhibition alters H3K4 methylation and disrupts the transcription start site as well.

Conclusions
Taken together, the data indicate that MEN1 contributes to STAT1-activated gene expression in a novel manner that includes defining the transcription start site and RNA processing.
The correlation between locomotor performance and hindlimb kinematics during burst locomotion in the Florida scrub lizard,Sceloporus woodi
Authors: McElroy Eric J. , Archambeau Kristen L. , McBrayer Lance D. 
Published: January 2012

SUMMARYBurst locomotion is thought to be closely linked to an organism's ability to survive and reproduce. During the burst, animals start from a standstill and then rapidly accelerate to near-maximum running speeds. Many previous studies have described the functional predictors of maximum running speed; however, only recently has work emerged that describes the morphological, functional and biomechanical underpinnings of acceleration capacity. Herein we present data on the three-dimensional hindlimb kinematics during burst locomotion, and the relationship between burst locomotor kinematics and locomotor performance in a small terrestrial lizard (Sceloporus woodi). We focus only on stance phase joint angular kinematics. Sceloporus woodi exhibited considerable variation in hindlimb kinematics and performance across the first three strides of burst locomotion. Stride 1 was defined by larger joint angular excursions at the knee and ankle; by stride 3, the knee and ankle showed smaller joint angular excursions. The hip swept through similar arcs across all strides, with most of the motion caused by femoral retraction and rotation. Metatarsophalangeal (MTP) kinematics exhibited smaller maximum angles in stride 1 compared with strides 2 and 3. The significant correlations between angular kinematics and locomotor performance were different across the first three strides. For stride 1, MTP kinematics predicted final maximum running speed; this correlation is likely explained by a correlation between stride 1 MTP kinematics and stride 2 acceleration performance. For stride 3, several aspects of joint kinematics at each joint predicted maximum running speed. Overall, S. woodi exhibits markedly different kinematics, performance and kinematics-performance correlations across the first three strides. This finding suggests that future studies of burst locomotion and acceleration performance should perform analyses on a stride-by-stride basis and avoid combining data from different strides across the burst locomotor event. Finally, the kinematics-performance correlations observed in S. woodi were quite different from those described for other species, suggesting that there is not a single kinematic pattern that is optimal for high burst performance.
Flexural stiffness of feather shafts: geometry rules over material properties
Authors: Bachmann Thomas , Emmerlich Jens , Baumgartner Werner , Schneider Jochen M. , Wagner Hermann 
Published: January 2012

SUMMARYFlight feathers of birds interact with the flow field during flight. They bend and twist under aerodynamic loads. Two parameters are mainly responsible for flexibility in feathers: the elastic modulus (Young's modulus, E) of the material (keratin) and the geometry of the rachises, more precisely the second moment of area (I). Two independent methods were employed to determine Young's modulus of feather rachis keratin. Moreover, the second moment of area and the bending stiffness of feather shafts from fifth primaries of barn owls (Tyto alba) and pigeons (Columba livia) were calculated. These species of birds are of comparable body mass but differ in wing size and flight style. Whether their feather material (keratin) underwent an adaptation in stiffness was previously unknown. This study shows that no significant variation in Young's modulus between the two species exists. However, differences in Young's modulus between proximal and distal feather regions were found in both species. Cross-sections of pigeon rachises were particularly well developed and rich in structural elements, exemplified by dorsal ridges and a well-pronounced transversal septum. In contrast, cross-sections of barn owl rachises were less profiled but had a higher second moment of area. Consequently, the calculated bending stiffness (EI) was higher in barn owls as well. The results show that flexural stiffness is predominantly influenced by the geometry of the feathers rather than by local material properties.
The polarization compass dominates over idiothetic cues in path integration of desert ants
Authors: Lebhardt Fleur , Koch Julja , Ronacher Bernhard 
Published: January 2012

SUMMARY
Desert ants, Cataglyphis, use the sky's pattern of polarized light as a compass reference for navigation. However, they do not fully exploit the complexity of this pattern, rather – as proposed previously – they assess their walking direction by means of an approximate solution based on a simplified internal template. Approximate rules are error-prone. We therefore asked whether the ants use additional cues to improve the accuracy of directional decisions, and focused on ‘idiothetic’ cues, i.e. cues based on information from proprioceptors. We trained ants in a channel system that was covered with a polarization filter, providing only a single e-vector direction as a directional ‘celestial’ cue. Then we observed their homebound runs on a test field, allowing full view of the sky. In crucial experiments, the ants were exposed to a cue conflict, in which sky compass and idiothetic information disagreed, by training them in a straight channel that provided a change in e-vector direction. The results indicated that the polarization information completely dominates over idiothetic cues. Two path segments with different e-vector orientations are combined linearly to a summed home vector. Our data provide additional evidence that Cataglyphis uses a simplified internal template to derive directional information from the sky's polarization pattern.
Origin and mechanism of thermal insensitivity in mole hemoglobins: a test of the ‘additional’ chloride binding site hypothesis
Authors: Signore Anthony V. , Stetefeld Jörg , Weber Roy E. , Campbell Kevin L. 
Published: January 2012

SUMMARY
The structural and evolutionary origins underlying the effect of temperature on the O2 binding properties of mammalian hemoglobins (Hbs) are poorly understood, despite their potential physiological importance. Previous work has shown that the O2 affinities of the blood of the coast mole (Scapanus orarius) and the eastern mole (Scalopus aquaticus) are significantly less sensitive to temperature changes than that of the star-nosed mole (Condylura cristata). It was suggested that this difference may arise from the binding of ‘additional’ chloride ions within a cationic pocket between residues 8His, 76Lys and 77Asn on the β-like δ-globin chains of coast and eastern mole Hbs. To test this hypothesis, we deduced the primary sequences of star-nosed mole and American shrew mole (Neurotrichus gibbsii) Hb, measured the sensitivity of these respiratory proteins to allosteric effector molecules and temperature, and calculated their overall oxygenation enthalpies (ΔH′). Here we show that the variability in ΔH′ seen among mole Hbs cannot be attributed to differential Cl– binding at δ8, δ76 and δ77, as the Cl– sensitivity of mole Hbs is unaffected by amino acid changes at this site (i.e. the proposed ‘additional’ Cl– binding site is not operational in mole Hbs). Rather, we demonstrate that the numerically low ΔH′ of coast and eastern mole Hbs results from heightened proton binding relative to other mole Hbs. Comparative sequence analysis and molecular modelling moreover suggest that this attribute evolved in a common ancestor of these two fossorial lineages and arises from the development of a salt bridge between a pair of amino acid residues (δ125His and α34Glu/Asp) that are not present in other mole Hbs.
Impaired puberty, fertility, and final stature in 45,X/46,XY mixed gonadal dysgenetic patients raised as boys
Authors: Martinerie Laetitia , Morel Yves , Gay Claire-Lise , Pienkowski Catherine , de Kerdanet Marc , Cabrol Sylvie , Lecointre Claudine , Coutant Regis , Baron Sabine , Colle Michel , Brauner Raja , Thibaud Elisabeth , Leger Juliane , Nihoul-Fekete Claire , Bouvattier Claire 
Published: January 2012

ContextGender assignment followed by surgery and hormonal therapy is a difficult decision in the management of 45,X/46,XY patients with abnormal external genitalia at birth considering the paucity of studies evaluating pubertal development and fertility outcome, most notably for patients raised as boys.ObjectiveThe purpose of this study was to describe the pubertal course of 20 45,X/46,XY patients born with ambiguous genitalia and raised as boys.MethodsThis is a multicenter retrospective study.ResultsMean age at study was 25.6±2.4 years. Eighty-five percent of the patients presented a ‘classical’ mixed gonadal dysgenetic phenotype at birth. Puberty was initially spontaneous in all but three boys, although in six other patients, testosterone therapy was subsequently necessary for completion of puberty. Sixty-seven percent of the remaining patients presented signs of declined testicular function at the end of puberty (increased levels of FSH and low levels of testosterone and/or inhibin B). Moreover, an abnormal structure of the Y chromosome, known to alter fertility, was found in 10 out of 16 (63%) patients. Two patients developed testicular cancer. Half of the patients have adult penile length of <80 mm. Mean adult height is 156.9±2 cm, regardless of GH treatment.ConclusionsIn summary, 45,X/46,XY children born with ambiguous genitalia and raised as boys have an altered pubertal course and impaired fertility associated with adult short stature, which should, therefore, be taken into consideration for the management of these patients.
A Microfluidic Assay for Measuring Electrical Conductivity of Gap Junction Channels
Authors: Bathany Cedric , Sachs Frederick , Hua Susan Z. 
Published: January 2012

ABSTRACTWe have developed a microfluidic sensor to measure the electrical coupling through gap junctions across a 2D sheet of cultured Normal Rat Kidney cells. The chip is based on a tri-stream laminar flow with conductive solutions on either end and a nonconductive solution in the middle stream. When an electrical voltage is applied, the current can only pass through the cell sheet, thereby enabling us to measure the electrical coupling of gap junctions between cells. Using this sensor we have measured the effect of 2-aminoethoxydiphenyl borate (2-APB) on Cx43 channels. We show that 2-APB reversibly inhibits electrical coupling of Cx43 in NRK cells. Moreover, we screened other potential candidates to block Cx43, 1-Heptanol and GsMTx-4, and examined their effects on Cx43 gap junctions.
Nanostructured Selenium for Preventing Biofilm Formation on Medical Devices
Authors: Wang Qi , Webster Thomas J. 
Published: January 2012

ABSTRACTBiofilms are a common cause of persistent infections on medical devices as they are easy to form and hard to treat. Selenium and its compounds are considered to be a novel material for a wide range of applications including anticancer applications and antibacterial applications. The objective of this study was to coat selenium nanoparticles on the surface of polycarbonate medical devices and examine their effectiveness at preventing biofilm formation. The results of this in vitro study showed that the selenium coating significantly inhibited Staphylococcus aureus growth on the surface of polycarbonate after 24 hours. Thus, this study suggests that coating polymers with nanostructured selenium is a fast and effective way to reduce bacteria functions leading to medical device infections.
Anisotropic Cellular Alignment on Nano-Wrinkled Polymeric Surface
Authors: Fujie Toshinori , Greco Francesco , Taccola Silvia , Ricotti Leonardo , Menciassi Arianna , Mattoli Virgilio 
Published: January 2012

ABSTRACTConvenient preparation of nano/micro scale topography is crucial for the fabrication of low-cost biodevices, which could be useful tools for understanding cell biology mechanisms and for the development of scaffolds for tissue engineering. Such intelligent surfaces have been conventionally fabricated through photolithography, micro-contact printing, and nano/micro imprinting. However, considering the process integration, these approaches are not always adequate in order to produce large dimensional patterns in a convenient and rapid way. In this study, we focused on the convenient fabrication of nano-wrinkles based on the elastic instability between a shape memory polymer sheet and a conductive polymeric film, on which the behavior of murine skeletal muscle cells (C2C12) was evaluated. A tens-of-nm-thick layer of poly(3,4-ethylenedioxythiophene) with poly(styrenesulfonate) (PEDOT:PSS) was spincoated on a thermo-retractable polymer sheet. Then, thermal treatment produced different periodicity of the unidirectional nano-wrinkles on the polymer sheet covered with different thickness of PEDOT:PSS layer. Finally, adhesion and proliferation of C2C12 were evaluated, comparing different samples. The cells preferentially adhered and anisotropically aligned on low and narrow ridges (1.5 μm height) rather than on high and wide ones (2.5 μm height). Furthermore, we observed that these trends were confirmed in the differentiation stage of C2C12 into myotubes. The combination of living cells and tunable nano-wrinkles made of conductive polymeric materials will represent a unique tool for the development of innovative biomedical devices.
Acoustic Energy: a New Tool for MEMS Manufacturing
Authors: Dussault D. , Dragoi V. 
Published: January 2012

ABSTRACTThe use of non-standard materials (e.g. specific substrates shapes and dimensions or polymer materials) for MEMS applications imposed a requirement for the development of new techniques for even well-established processes. Acoustic energy in the MHz frequency range has been used in the semiconductor industry for various processes such as photoresist development, substrate cleaning and electro-plating enhancement. The work presented here is focusing on single wafer cleaning and on photoresist development.The cleaning process developed addresses mainly wafer cleaning prior to wafer bonding processes, in which particle contamination is of crucial importance.The photoresist development process was developed mainly for thick resist layers development (few hundreds of μm) in order to improve definition of high aspect ratio features but was used as well as a significant process time reduction factor for development of regular thickness resists (few μm).