bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of cryogenic cooling on surface layer alterations in machining of AISI 52100 steels
Authors: Umbrello D , Yang S , Dillon O W , Jawahir I S
Published: November 2012

Microstructural phase transformations, commonly known as white layer formation in hard turned steel components, have in recent times become an interesting research topic in machining as they are related to the surface integrity and functional performance of components. Three main theories have been proposed to justify the mechanisms of white layer formation: (1) rapid heating and quenching; (2) severe plastic deformation; and (3) surface reaction with the environment. Coolant application also affects the surface microstructural alterations resulting from machining operations, which have a significant influence on product performance and life. The present work aims at understanding the effects of cryogenic coolant application on the machined surface alterations during machining of hardened AISI 52100 bearing steel. Experiments were performed under dry and cryogenic cooling conditions using cubic boron nitride tool inserts with varying initial work material hardness, tool shape, cutting speed and feedrate. Optical and scanning electron microscopes (SEM) were used to analyse the affected layer in the machined subsurface, while X-ray diffraction technique was utilised to investigate the microstructural phase composition. The experimental results prove that the microstructural phase changes are heavily influenced by the cutting process parameters and the use of cryogenic cooling, in some cases leading to the total removal of martensite.
Corrosion resistance of organic coating pretreated by phytic acid
Authors: Cui X F , Jin G , Liu E B , Wang Z Y , Liu Z , Li Q F , Wang F H
Published: November 2012

In this study, phytic acid pretreatment is used as a substitute for toxic chromate pretreatment to improve the corrosion resistance of organic coating on AZ91D magnesium alloys. The microstructures of phytic acid conversion films are observed by a transmission electron microscope. The role of phytic acid pretreatment on the corrosion resistance of organic coating is investigated using salt spray test and electrochemical impedance spectroscopy. The experimental results show that the phytic acid conversion film exhibits a dense amorphous structure and phytic acid pretreatment can effectively improve the corrosion resistance of organic coating on magnesium alloys.
‘It is Ridiculous that the Borough Librarian of Croydon Should Decide the Policy of the Scottish Education Department’: The Establishment of Scotland’s Second Library School
Authors: Reid Peter H
Published: November 2012

In the middle of the 1960s, amid concerns about the direction of professional education in Scotland and problems with the number of places available for those to wishing to study librarianship, there emerged a strongly nationalistic debate surrounding proposals to establish a second school of librarianship in Scotland. The process of establishing that second school at Robert Gordon’s Institute of Technology in Aberdeen became protracted and fraught with difficulties. It was characterized by disputes and misunderstandings between the Library Association and the Scottish Library Association. Many of these differences of opinion took on a distinctly nationalistic quality and the debate within the library community at the time can be said to offer wider, allegorical lessons for the changing political landscape between Scotland and the rest of the United Kingdom. This article outlines this debate, principally from the perspective of the members of Scottish librarianship community. It draws extensively on a hitherto private archive of correspondence of those directly involved.
A diploid wheat TILLING resource for wheat functional genomics
Authors: Rawat Nidhi , Sehgal Sunish K , Joshi Anupama , Rothe Nolan , Wilson Duane L , McGraw Nathan , Vadlani Praveen V , Li Wanlong , Gill Bikram S
Published: November 2012

Background

Triticum monococcum L., an A genome diploid einkorn wheat, was the first domesticated crop. As a diploid, it is attractive genetic model for the study of gene structure and function of wheat-specific traits. Diploid wheat is currently not amenable to reverse genetics approaches such as insertion mutagenesis and post-transcriptional gene silencing strategies. However, TILLING offers a powerful functional genetics approach for wheat gene analysis.

Results

We developed a TILLING population of 1,532 M2 families using EMS as a mutagen. A total of 67 mutants were obtained for the four genes studied. Waxy gene mutation frequencies are known to be 1/17.6 - 34.4 kb DNA in polyploid wheat TILLING populations. The T. monococcum diploid wheat TILLING population had a mutation frequency of 1/90 kb for the same gene. Lignin biosynthesis pathway genes- COMT1, HCT2, and 4CL1 had mutation frequencies of 1/86 kb, 1/92 kb and 1/100 kb, respectively. The overall mutation frequency of the diploid wheat TILLING population was 1/92 kb.

Conclusion

The mutation frequency of a diploid wheat TILLING population was found to be higher than that reported for other diploid grasses. The rate, however, is lower than tetraploid and hexaploid wheat TILLING populations because of the higher tolerance of polyploids to mutations. Unlike polyploid wheat, most mutants in diploid wheat have a phenotype amenable to forward and reverse genetic analysis and establish diploid wheat as an attractive model to study gene function in wheat. We estimate that a TILLING population of 5, 520 will be needed to get a non-sense mutation for every wheat gene of interest with 95% probability.
A comparative study of 22-channel water-perfusion system and solid-state system with 36-sensors in esophageal manometery
Authors: Wang Kun , Duan Li-ping , Ge Ying , Xia Zhi-wei , Xu Zhi-jie
Published: November 2012

Background

To compare the characteristics between 22-channel water-perfusion manometry (WPM) and solid-state manometry (SSM) with 36 sensors of the pressure measurements, as well as patients’ discomfort indices in nose and pharynx, the preparation and operation time of the manometry.

Methods

12 volunteers were included in the study. Each of the volunteers underwent esophageal manometry by both 22-channel water-perfusion catheter (WPC) and solid-state catheter (SSC) with 36 sensors in random order, and separated by 30 min. The subjects gave a VAS score soon after each test. Non-parametric tests were used to analyze the differences and Bland-Altman plots were used to assess the consistency of the two systems.

Results

During the wet swallows, there were significant differences between the two systems in three measurements of location of lower esophageal sphincter (LES) upper margin (Z = -2.11, P = 0.035), LES relax ratio (Z = -2.20, P = 0.028) and IRP4s (Z = -2.05, P = 0.041). During the jelly pocket swallows, LES relax ratio measurements of the two systems showed significant differences (Z = -2.805, P = 0.005). Further Bland–Altman plots analysis presented good agreement between the two systems measurements of location of LES upper margin, LES relax ratio and IRP4s. The discomfort indices of subjects’ nasal sensation were higher when inserting the solid-state catheter [5(3.75-5)] than water-perfusion one (2.5(2-4)) (Z = -2.471, P = 0.013), as well as the discomfort indices of pharyngeal sensation (7.5(4.75-9) vs. 4.5(3.75-6.5)), (Z = -2.354, P = 0.019). The preparation time for WPC was 40(39-41) minutes, which was much longer than that for SSC 32.5(31.75-33) minutes, (Z = -3.087, P = 0.002). And the nurses reported it’s much easier to insert WPC (Z = -3.126, P = 0.002).

Conclusions

In conclusion, most pressure measurements were consistent between WPM and SSM. Patients tolerated better with WPC, while for operators, the SSC presented more convenient.
Ethnicity and elevated liver transaminases among newly diagnosed children with type 2 diabetes
Authors: Hudson Omar D , Nunez Martha , Shaibi Gabriel Q
Published: November 2012

Background

To examine the influence of ethnicity on liver transaminases among adolescents with type 2 diabetes mellitus (T2DM).

Methods

A retrospective medical chart review of 57 (30 males and 27 females) newly diagnosed patients with T2DM. Ethnicity was determined by self-report and height, weight, body mass index (BMI) and glycosylated hemoglobin (HbA1c) were obtained using standard clinical procedures. Fasting levels of alanine aminotransaminase (ALT) and aspartate aminotransferase (AST) were collected prior to the initiation of any therapy.

Results

Age, gender, height, weight, BMI, and HbA1c did not differ between ethnic groups. Compared to African-Americans, Hispanics had significantly higher ALT (23.9 ± 3.4 vs. 107.8 ± 20.3, p=0.002) and AST (17.7 ± 2.5 vs. 71.1 ± 15.7, p<0.001) and were significantly more likely to have ALT values above the upper limit of normal (20% vs. 71%, p=0.005) and twice the upper limit of normal (0% vs. 39%, p=0.05) as well as AST values above the upper limit of normal (0% vs. 53%, p=0.002). No differences in ALT or AST were found between Hispanics and non-Hispanic whites or between African-Americans and non-Hispanic whites.

Conclusions

These preliminary findings suggest that Hispanic children with T2DM may be at higher risk for developing non-alcoholic fatty liver disease and indicate that a comprehensive hepatic evaluation is warranted in this population. Future studies that incorporate more precise and proximal measures of liver health are warranted in this population.
Contextual determinants of health behaviours in an aboriginal community in Canada: pilot project
Authors: Joseph Pamela , Davis A Darlene , Miller Ruby , Hill Karen , McCarthy Honey , Banerjee Ananya , Chow Clara , Mente Andrew , Anand Sonia S
Published: November 2012

Background

Rapid change in food intake, physical activity, and tobacco use in recent decades have contributed to the soaring rates of obesity, type 2 diabetes and cardiovascular disease (CVD) in Aboriginal populations living in Canada. The nature and influence of contextual factors on Aboriginal health behaviours are not well characterized.

Methods

To describe the contextual determinants of health behaviours associated with cardiovascular risk factors on the Six Nations reserve, including the built environment, access and affordability of healthy foods, and the use of tobacco.

In this cross-sectional study, 63 adults from the Six Nations Reserve completed the modified Neighbourhood Environment Walkability Scale (NEWS), questionnaire assessing food access and availability, tobacco pricing and availability, and the Environmental Profile of Community Health (EPOCH) tool.

Results

The structured environment of Six Nations Reserve scored low for walkability, street connectivity, aesthetics, safety, and access to walking and cycling facilities. All participants purchased groceries off-reserve, although fresh fruits and vegetables were reported to be available and affordable both on and off-reserve. On average $151/week is spent on groceries per family. Ninety percent of individuals report tobacco use is a problem in the community. Tobacco is easily accessible for children and youth, and only three percent of community members would accept increased tobacco taxation as a strategy to reduce tobacco access.

Conclusions

The built environment, access and affordability of healthy food and tobacco on the Six Nations Reserve are not perceived favourably. Modification of these contextual factors described here may reduce adverse health behaviours in the community.
Some southern African plant species used to treat helminth infections in ethnoveterinary medicine have excellent antifungal activities
Authors: Adamu Mathew , Naidoo Vinasan , Eloff Jacobus N
Published: November 2012

Background

Diseases caused by microorganisms and parasites remain a major challenge globally and particularly in sub-Saharan Africa to man and livestock. Resistance to available antimicrobials and the high cost or unavailability of antimicrobials complicates matters. Many rural people use plants to treat these infections. Because some anthelmintics e.g. benzimidazoles also have good antifungal activity we examined the antifungal activity of extracts of 13 plant species used in southern Africa to treat gastrointestinal helminth infections in livestock and in man.

Methods

Antifungal activity of acetone leaf extracts was determined by serial microdilution with tetrazolium violet as growth indicator against Aspergillus fumigatus, Cryptococcus neoformans and Candida albicans. These pathogens play an important role in opportunistic infections of immune compromised patients. Cytotoxicity was determined by MTT cellular assay. Therapeutic indices were calculated and selectivity for different pathogens determined. We proposed a method to calculate the relation between microbicidal and microbistatic activities. Total activities for different plant species were calculated.

Results

On the whole, all 13 extracts had good antifungal activities with MIC values as low as 0.02 mg/mL for extracts of Clausena anisata against Aspergillus fumigatus a nd 0.04 mg/mL for extracts of Zanthoxylum capense, Clerodendrum glabrum, and Milletia grandis, against A. fumigatus. Clausena anisata extracts had the lowest cytotoxicity (LC50) of 0.17 mg/mL, a reasonable therapeutic index (2.65) against A. fumigatus. It also had selective activity against A. fumigatus, an overall fungicidal activity of 98% and a total activity of 3395 mL/g against A. fumigatus. This means that 1 g of acetone leaf extract can be diluted to 3.4 litres and it would still inhibit the growth. Clerodendrum glabrum, Zanthoxylum capense and Milletia grandis extracts also yielded promising results.

Conclusions

Some plant extracts used for treatment of parasitic infections also have good antifungal activity. Because it is much easier to isolate antifungal compounds by bioassay guided fractionation, this approach may facilitate the isolation of anthelmintic compounds from active plant extracts. The viability of this approach can be tested by isolating the antifungal compounds and then determining its anthelmintic activity. Some of these plant extracts may also be useful in combating fungal infections.
The role of A20 in the pathogenesis of lymphocytic malignancy
Authors: Zhang Fan , Yang Lijiang , Li Yangqiu
Published: November 2012

Autoimmune phenomena were identified in many different cases of hematological diseases and solid tumors, which may be due to alterations in the expression and function of the NF-κB signaling pathway. Recently, a number of studies have shown that the deletion or mutation of A20, a negative regulator of NF-κB, is frequently found in lymphomas, suggesting that it may be a linker between the altered immune response and leukemogenesis. The aim of this review is to summarize current findings of the A20 biological functions and its molecular mechanism as a tumor suppressor and immune regulator. The identification of A20 mutations and deletions in lymphocytic malignancy and the predictive significance of these aberrations are also reviewed.
A comparison of E15.5 fetus and newborn rat serum proteomes
Authors: Wei Lilong , Jia Lulu , Zhu Lisi , Ma Sucan , Zhang Dan , Shao Chen , Sun Wei , Gao Youhe
Published: November 2012

Background

Serum proteins carry out several functions in the circulation, including transfer, immunological functions, messenger functions, coagulation, and regulation of homeostasis. To investigate changes in serum proteins that occur during development, the serum proteomes of embryonic 15.5 (E15.5) fetuses and newborn rats were compared using LC-MS/MS.

Results

A total of 958 proteins were identified in the serum of rats at both developmental stages. The serum proteome pattern of newborn rats was compared to E15.5 fetuses by relative quantitation. The expression patterns of hemoglobin subunits were different at the two stages, with most of the subunits having decreased expression in newborn rats compared to E15.5 fetuses. In addition, 8 of 12 apolipoproteins were significantly decreased and 10 of 11 identified complement molecules were increased, with 4 exhibiting a significant increase. Moreover, 11 of 14 of the significantly increased enzyme regulators were inhibitors. The serum proteome patterns of different littermates from both developmental stages were also compared. We found that the levels of many highly abundant serum proteins varied between littermates, and the variations were larger than the variations of the technical control.

Conclusions

The serum proteomes of newborn rats and E15.5 fetuses were compared. The expression patterns of hemoglobin subunits were different at the two developmental stages, with most of the subunits having decreased expression. The majority of apolipoproteins had significantly decreased expression, while almost all identified complement proteins had increased expression. The levels of several highly abundant serum proteins also varied among littermates at these two developmental stages. This is the first study using LC-MS/MS to investigate serum proteome development.
Activity of pemetrexed and high-dose gefitinib in an EGFR-mutated lung adenocarcinoma with brain and leptomeningeal metastasis after response to gefitinib
Authors: Yuan Ying , Tan Chunwen , Li Modan , Shen Hong , Fang Xuefeng , Hu Yinghong , Ma Shenglin
Published: November 2012

About 20% to 40% of patients with non-small cell lung cancer (NSCLC) will develop brain metastases during the natural course of their disease. The prognosis for such patients is very poor with limited survival. In addition to the standard whole brain radiation therapy (WBRT), some studies have shown that chemotherapy drugs and/or epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) can improve the outcome of these patients. Here, we report a stage IIIA patient who developed multiple brain metastases one year after operation. Oral gefitinib with concurrent WBRT were given as first-line therapy. Complete response and a 50-month progression-free survival (PFS) were obtained. Double dosage of gefitinib (500 mg per day) together with pemetrexed were given as the second-line therapy after the patient developed new brain lesions and leptomeningeal metastasis during the maintenance therapy of gefitinib. The PFS for the second-line therapy was six months. In total, the patient obtained an overall survival of 59 months since the first diagnosis of brain metastases. Mutational analysis showed a 15-nucleotide deletion and a missense mutation in exon 19 of the EGFR gene, and a missense mutation at codon 12 of the K-ras gene. These underlying genetic changes might partially explain the long-term survival of this patient after brain metastases when treated with concurrent or sequential therapies of EGFR-TKI, radiotherapy and chemotherapy.
Phosphotyrosine recognition domains: the typical, the atypical and the versatile
Authors: Kaneko Tomonori , Joshi Rakesh , Feller Stephan M , Li Shawn SC
Published: November 2012

SH2 domains are long known prominent players in the field of phosphotyrosine recognition within signaling protein networks. However, over the years they have been joined by an increasing number of other protein domain families that can, at least with some of their members, also recognise pTyr residues in a sequence-specific context. This superfamily of pTyr recognition modules, which includes substantial fractions of the PTB domains, as well as much smaller, or even single member fractions like the HYB domain, the PKCδ and PKCθ C2 domains and RKIP, represents a fascinating, medically relevant and hence intensely studied part of the cellular signaling architecture of metazoans. Protein tyrosine phosphorylation clearly serves a plethora of functions and pTyr recognition domains are used in a similarly wide range of interaction modes, which encompass, for example, partner protein switching, tandem recognition functionalities and the interaction with catalytically active protein domains. If looked upon closely enough, virtually no pTyr recognition and regulation event is an exact mirror image of another one in the same cell. Thus, the more we learn about the biology and ultrastructural details of pTyr recognition domains, the more does it become apparent that nature cleverly combines and varies a few basic principles to generate a sheer endless number of sophisticated and highly effective recognition/regulation events that are, under normal conditions, elegantly orchestrated in time and space. This knowledge is also valuable when exploring pTyr reader domains as diagnostic tools, drug targets or therapeutic reagents to combat human diseases.
Quantum conductance of silicon-doped carbon wire nanojunctions
Authors: Szczȩśniak Dominik , Khater Antoine , Ba̧k Zygmunt , Szczȩśniak Radosław , Ghantous Michel Abou
Published: November 2012

Unknown quantum electronic conductance across nanojunctions made of silicon-doped carbon wires between carbon leads is investigated. This is done by an appropriate generalization of the phase field matching theory for the multi-scattering processes of electronic excitations at the nanojunction and the use of the tight-binding method. Our calculations of the electronic band structures for carbon, silicon, and diatomic silicon carbide are matched with the available corresponding density functional theory results to optimize the required tight-binding parameters. Silicon and carbon atoms are treated on the same footing by characterizing each with their corresponding orbitals. Several types of nanojunctions are analyzed to sample their behavior under different atomic configurations. We calculate for each nanojunction the individual contributions to the quantum conductance for the propagatingσ,Π, andσ∗electron incidents from the carbon leads. The calculated results show a number of remarkable features, which include the influence of the ordered periodic configurations of silicon-carbon pairs and the suppression of quantum conductance due to minimum substitutional disorder and artificially organized symmetry on these nanojunctions. Our results also demonstrate that the phase field matching theory is an efficient tool to treat the quantum conductance of complex molecular nanojunctions.
Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy
Authors: Kandadi Machender R , Yu Xuejun , Frankel Arthur E , Ren Jun
Published: November 2012

Background

Lethal and edema toxins secreted byBacillus anthracisduring anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction.

Methods

Wild type (WT) and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.)). Cardiomyocyte contractile and intracellular Ca2+properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination.

Results

Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca2+handling), the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies.

Conclusions

Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca2+anomalies, possibly through regulation of autophagy and mitochondrial function.
Intercellular Communication within the Rat Anterior Pituitary Gland. XV. Properties of Spontaneous and LHRH-Induced Ca2+ Transients in the Transitional Zone of the Rat Anterior Pituitary in Situ
Authors: Hattori Kazuki , Shirasawa Nobuyuki , Suzuki Hikaru , Otsuka Takanobu , Wada Ikuo , Yashiro Takashi , Herbert Damon C , Soji Tsuyoshi , Hashitani Hikaru
Published: November 2012

In the transitional zone of the rat anterior pituitary, spontaneous and LHRH-induced Ca2+ dynamics were visualized using fluo-4 fluorescence Ca2+ imaging. A majority of cells exhibited spontaneous Ca2+ transients, while small populations of cells remained quiescent. Approximately 70% of spontaneously active cells generated fast, oscillatory Ca2+ transients that were inhibited by cyclopiazonic acid (10 μm) but not nicardipine (1 μm), suggesting that Ca2+ handling by endoplasmic reticulum, but not Ca2+ influx through voltage-dependent L-type Ca2+ channels, plays a fundamental role in their generation. In the adult rat anterior pituitary, LHRH (100 μg/ml) caused a transient increase in the Ca2+ level in a majority of preparations taken from the morning group rats killed between 0930 h and 1030 h. However, the second application of LHRH invariably failed to elevate Ca2+ levels, suggesting that the long-lasting refractoriness to LHRH stimulation was developed upon the first challenge of LHRH. In contrast, LHRH had no effect in most preparations taken from the afternoon group rats euthanized between 1200 h and 1400 h. In the neonatal rat anterior pituitary, LHRH caused a suppression of spontaneous Ca2+ transients. Strikingly, the second application of LHRH was capable of reproducing the suppression of Ca2+ signals, indicating that the refractoriness to LHRH had not been established in neonatal rats. These results suggest that responsiveness to LHRH has a long-term refractoriness in adult rats, and that the physiological LHRH surge may be clocked in the morning. Moreover, LHRH-induced excitation and associated refractoriness appear to be incomplete in neonatal rats and may be acquired during development.
Ligand-Dependent Actions of the Vitamin D Receptor Are Required for Activation of TGF-β Signaling during the Inflammatory Response to Cutaneous Injury
Authors: Luderer Hilary F. , Nazarian Rosalynn M. , Zhu Eric D. , Demay Marie B.
Published: November 2012

The vitamin D receptor (VDR) has both 1,25-dihydroxyvitamin D-dependent and -independent actions in the epidermis. Ligand-dependent actions of the VDR have been shown to promote keratinocyte differentiation and to regulate formation of the epidermal barrier. In contrast, the actions of the VDR that regulate postmorphogenic hair cycling do not require 1,25-dihydroxyvitamin D. The VDR also has immunomodulatory actions that are dependent on its ligand, 1,25-dihydroxyvitamin D. To determine whether the ligand-dependent or -independent actions of the VDR regulate the inflammatory response to cutaneous injury, studies were performed in control, VDR knockout, and vitamin D-deficient mice. These investigations demonstrate that absence of receptor or ligand impairs the dermal response to cutaneous injury. Although neutrophil recruitment is not affected, the absence of VDR signaling leads to defects in macrophage recruitment and granulation tissue formation. Studies performed to identify the molecular basis for this phenotype demonstrate that absence of the VDR, or its ligand, impairs TGF-β signaling in the dermis, characterized by decreased expression of monocyte chemotactic protein-1 and reduced phosphorylation of phosphorylated Smad-3 as well as attenuated phosphorylated Smad-3 phosphorylation in response to TGF-β in primary dermal fibroblasts lacking the VDR. Thus, these data demonstrate that the liganded VDR interacts with the TGF-β signaling pathway to promote the normal inflammatory response to cutaneous injury.
The where, when and how of microtubule nucleation – one ring to rule them all
Authors: Teixidó-Travesa Neus , Roig Joan , Lüders Jens
Published: November 2012

The function of microtubules depends on their arrangement into highly ordered arrays. Spatio-temporal control over the formation of new microtubules and regulation of their properties are central to the organization of these arrays. The nucleation of new microtubules requires γ-tubulin, an essential protein that assembles into multi-subunit complexes and is found in all eukaryotic organisms. However, the way in which γ-tubulin complexes are regulated and how this affects nucleation and, potentially, microtubule behavior, is poorly understood. γ-tubulin has been found in complexes of various sizes but several lines of evidence suggest that only large, ring-shaped complexes function as efficient microtubule nucleators. Human γ-tubulin ring complexes (γTuRCs) are composed of γ-tubulin and the γ-tubulin complex components (GCPs) 2, 3, 4, 5 and 6, which are members of a conserved protein family. Recent work has identified additional unrelated γTuRC subunits, as well as a large number of more transient γTuRC interactors. In this Commentary, we discuss the regulation of γTuRC-dependent microtubule nucleation as a key mechanism of microtubule organization. Specifically, we focus on the regulatory roles of the γTuRC subunits and interactors and present an overview of other mechanisms that regulate γTuRC-dependent microtubule nucleation and organization.
Delineating the core regulatory elements crucial for directed cell migration by examining folic-acid-mediated responses
Authors: Srinivasan Kamalakkannan , Wright Gus A. , Hames Nicole , Housman Max , Roberts Alayna , Aufderheide Karl J. , Janetopoulos Chris
Published: November 2012

Dictyostelium discoideum shows chemotaxis towards folic acid (FA) throughout vegetative growth, and towards cAMP during development. We determined the spatiotemporal localization of cytoskeletal and signaling molecules and investigated the FA-mediated responses in a number of signaling mutants to further our understanding of the core regulatory elements that are crucial for cell migration. Proteins enriched in the pseudopods during chemotaxis also relocalize transiently to the plasma membrane during uniform FA stimulation. In contrast, proteins that are absent from the pseudopods during migration redistribute transiently from the PM to the cytosol when cells are globally stimulated with FA. These chemotactic responses to FA were also examined in cells lacking the GTPases Ras C and G. Although Ras and phosphoinositide 3-kinase activity were significantly decreased in Ras G and Ras C/G nulls, these mutants still migrated towards FA, indicating that other pathways must support FA-mediated chemotaxis. We also examined the spatial movements of PTEN in response to uniform FA and cAMP stimulation in phospholipase C (PLC) null cells. The lack of PLC strongly influences the localization of PTEN in response to FA, but not cAMP. In addition, we compared the gradient-sensing behavior of polarized cells migrating towards cAMP to that of unpolarized cells migrating towards FA. The majority of polarized cells make U-turns when the cAMP gradient is switched from the front of the cell to the rear. Conversely, unpolarized cells immediately extend pseudopods towards the new FA source. We also observed that plasma membrane phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] levels oscillate in unpolarized cells treated with Latrunculin-A, whereas polarized cells had stable plasma membrane PtdIns(3,4,5)P3 responses toward the chemoattractant gradient source. Results were similar for cells that were starved for 4 hours, with a mixture of polarized and unpolarized cells responding to cAMP. Taken together, these findings suggest that similar components control gradient sensing during FA- and cAMP-mediated motility, but the response of polarized cells is more stable, which ultimately helps maintain their directionality.
Glutathione peroxidase 3, a new retinoid target gene, is crucial for human skeletal muscle precursor cell survival
Authors: El Haddad Marina , Jean Elise , Turki Ahmed , Hugon Gérald , Vernus Barbara , Bonnieu Anne , Passerieux Emilie , Hamade Aline , Mercier Jacques , Laoudj-Chenivesse Dalila , Carnac Gilles
Published: November 2012

Protection of satellite cells from cytotoxic damages is crucial to ensure efficient adult skeletal muscle regeneration and to improve therapeutic efficacy of cell transplantation in degenerative skeletal muscle diseases. It is therefore important to identify and characterize molecules and their target genes that control the viability of muscle stem cells. Recently, we demonstrated that high aldehyde dehydrogenase activity is associated with increased viability of human myoblasts. In addition to its detoxifying activity, aldehyde dehydrogenase can also catalyze the irreversible oxidation of vitamin A to retinoic acid; therefore, we examined whether retinoic acid is important for myoblast viability. We showed that when exposed to oxidative stress induced by hydrogen peroxide, adherent human myoblasts entered apoptosis and lost their capacity for adhesion. Pre-treatment with retinoic acid reduced the cytotoxic damage ex vivo and enhanced myoblast survival in transplantation assays. The effects of retinoic acid were maintained in dystrophic myoblasts derived from facioscapulohumeral patients. RT-qPCR analysis of antioxidant gene expression revealed glutathione peroxidase 3 (Gpx3), a gene encoding an antioxidant enzyme, as a potential retinoic acid target gene in human myoblasts. Knockdown of Gpx3 using short interfering RNA induced elevation in reactive oxygen species and cell death. The anti-cytotoxic effects of retinoic acid were impaired in GPx3-inactivated myoblasts, which indicates that GPx3 regulates the antioxidative effects of retinoic acid. Therefore, retinoid status and GPx3 levels may have important implications for the viability of human muscle stem cells.
Keratin 1 maintains skin integrity and participates in an inflammatory network in skin via interleukin-18
Authors: Roth Wera , Kumar Vinod , Beer Hans-Dietmar , Richter Miriam , Wohlenberg Claudia , Reuter Ursula , Thiering Sören , Staratschek-Jox Andrea , Hofmann Andrea , Kreusch Fatima , Schultze Joachim L , Vogl Thomas , Roth Johannes , Hausser Ingrid , Magin Thomas M
Published: November 2012

Keratin 1 (KRT1) and its heterodimer partner keratin 10 (KRT10) are major constituents of the intermediate filament cytoskeleton in suprabasal epidermis. KRT1 mutations cause epidermolytic ichthyosis in humans, characterized by loss of barrier integrity and recurrent erythema. In search of the largely unknown pathomechanisms and the role of keratins in barrier formation and inflammation control, we show here that Krt1 is crucial for maintenance of skin integrity and participates in an inflammatory network in murine keratinocytes. Absence of Krt1 caused a prenatal increase in interleukin-18 (IL-18) and S100A8/A9, accompanied by a barrier defect and perinatal lethality. Depletion of IL-18 partially rescued Krt1−/− mice. IL-18 release was keratinocyte-autonomous, KRT1- and caspase-1-dependent, supporting an upstream role of KRT1 in the pathology. Finally, transcriptome profiling revealed a Krt1-mediated gene expression signature similar to atopic eczema (AE) and psoriasis, but different from Krt5-deficiency and epidermolysis bullosa simplex (EBS). Our data suggest a functional link between KRT1 and human inflammatory skin diseases.
Structure, innervation and response properties of integumentary sensory organs in crocodilians
Authors: Leitch Duncan B. , Catania Kenneth C.
Published: November 2012

Integumentary sensory organs (ISOs) are densely distributed on the jaws of crocodilians and on body scales of members of the families Crocodilidae and Gavialidae. We examined the distribution, anatomy, innervation and response properties of ISOs on the face and body of crocodilians and documented related behaviors for an alligatorid (Alligator mississippiensis) and a crocodylid (Crocodylus niloticus). Each of the ISOs (roughly 4000 in A. mississippiensis and 9000 in C. niloticus) was innervated by networks of afferents supplying multiple different mechanoreceptors. Electrophysiological recordings from the trigeminal ganglion and peripheral nerves were made to isolate single-unit receptive fields and to test possible osmoreceptive and electroreceptive functions. Multiple small (<0.1 mm2) receptive fields, often from a single ISO, were recorded from the premaxilla, the rostral dentary, the gingivae and the distal digits. These responded to a median threshold of 0.08 mN. The less densely innervated caudal margins of the jaws had larger receptive fields (>100 mm2) and higher thresholds (13.725 mN). Rapidly adapting, slowly adapting type I and slowly adapting type II responses were identified based on neuronal responses. Several rapidly adapting units responded maximally to vibrations at 20–35 Hz, consistent with reports of the ISOs' role in detecting prey-generated water surface ripples. Despite crocodilians' armored bodies, the ISOs imparted a mechanical sensitivity exceeding that of primate fingertips. We conclude that crocodilian ISOs have diverse functions, including detection of water movements, indicating when to bite based on direct contact of pursued prey, and fine tactile discrimination of items held in the jaws.
Dine or dash? Turbulence inhibits blue crab navigation in attractive–aversive odor plumes by altering signal structure encoded by the olfactory pathway
Authors: Weissburg Marc , Atkins Lorin , Berkenkamp Kimberly , Mankin Danielle
Published: November 2012

Blue crabs can distinguish and navigate to attractive (food) odors even when aversive odors (injured crab metabolites) are released nearby. Blue crabs in these conditions detect the aversive odor and avoid it, but find the attractive source with nearly the same success rate as when the attractive source is presented alone. Spatially and temporally distinct odor filaments appear to signal to foragers that the two odor sources are not co-located, and hence navigating to the attractive odor entails an acceptable risk of predation. However, environmentally produced turbulence suppresses tracking by homogenizing the two odors; blue crabs fail to track to the attractive source when the aversive source is present, even though turbulence does not substantially inhibit tracking to the attractive source alone. Removal of sensory input from aesthetascs on the antennules, but not chemosensors on the legs, rescues navigation to attractive–aversive dual plumes in turbulent conditions. These results suggest that mixing in the natural environment may amplify the effects of predators by suppressing tracking to food odors when aversive cues are present, and that the olfactory pathway mediates the response.
Evidence-based facilities design in health care: a study of aged care facilities in Australia
Authors: Fleming Richard , Fay Roger , Robinson Andrew
Published: November 2012

Many facilities for people with dementia have been built with little translation of the substantial body of evidence available to inform design. Knowledge translation has been described as a four-stage process: awareness, agreement, adoption and adherence. This paper identifies where knowledge translation fails in the design of aged care facilities for people with dementia. Ten aged care facilities were audited using the Environmental Audit Tool. Senior managers and architects involved in the facility design were then interviewed to ascertain their knowledge of evidence-based principles of dementia design, their agreement with the principles and the nature of the obstacles they had encountered in their implementation. All architects claimed at least partial awareness of the design principles. Five facility managers claimed full awareness. Those facilities designed with the input of managers who were fully aware of the principles were of significantly higher design quality. There was little agreement on the significance of other obstacles. Once aged care providers are aware of the principles, they appear to find ways to implement them. If the next generation of residential aged care facilities is to be suitable for people with dementia, the facility managers must be made aware of the available design principles, architects encouraged to be more active in sharing their knowledge and ways found to improve the exchange of knowledge between the parties.
Use of a Fogarty catheter after tracheobronchial inhalation of a bead
Authors: Landy Christian , Massoure Pierre-Laurent , Gauthier Jerome , Eve Olivier , Kaiser Eric
Published: November 2012

We describe a case of tracheobronchial inhalation of a bead by a five-year-old girl in Djibouti. The bead was extracted using a Fogarty balloon catheter passed through the rigid bronchoscope without complication. This kind of accident is not exceptional and we discuss the management of such cases with limited diagnostic tools and therapeutic environments.
Semi-Blind Spectral Deconvolution with Adaptive Tikhonov Regularization
Authors: Yan Luxin , Liu Hai , Zhong Sheng , Fang Houzhang
Published: November 2012

Deconvolution has become one of the most used methods for improving spectral resolution. Deconvolution is an ill-posed problem, especially when the point spread function (PSF) is unknown. Non-blind deconvolution methods use a predefined PSF, but in practice the PSF is not known exactly. Blind deconvolution methods estimate the PSF and spectrum simultaneously from the observed spectra, which become even more difficult in the presence of strong noise. In this paper, we present a semi-blind deconvolution method to improve the spectral resolution that does not assume a known PSF but models it as a parametric function in combination with the a priori knowledge about the characteristics of the instrumental response. First, we construct the energy functional, including Tikhonov regularization terms for both the spectrum and the parametric PSF. Moreover, an adaptive weighting term is devised in terms of the magnitude of the first derivative of spectral data to adjust the Tikhonov regularization for the spectrum. Then we minimize the energy functional to obtain the spectrum and the parameters of the PSF. We also discuss how to select the regularization parameters. Comparative results with other deconvolution methods on simulated degraded spectra, as well as on experimental infrared spectra, are presented.
Deep-Ultraviolet (UV) Resonance Raman Spectroscopy as a Tool for Quality Control of Formulated Therapeutic Proteins
Authors: Arzhantsev Sergey , Vilker Vincent , Kauffman John
Published: November 2012

A deep-ultraviolet (UV) Raman spectrometer with excitation source tunable from 193 to 210 nm has been built and characterized. The dispersion of the spectrometer over the entire range was measured and described theoretically. The relative sensitivity of the spectrometer was estimated using the integrated intensity ratio of two Raman bands of cyclohexane. Resonance Raman spectra of three formulated insulin products were measured and compared. A band-targeted entropy minimization algorithm was applied to the collected spectra for mixture analysis of insulin products. We conclude that it is feasible to develop robust qualitative methods for quality control of protein-based formulated drug using DUVRR spectroscopy.
Chemometric Method of Spectra Analysis Leading to Isolation of Lysozyme and CtDNA Spectra Affected by Osmolytes
Authors: Bruździak Piotr , Rakowska Paulina W. , Stangret Janusz
Published: November 2012

In this paper we present a chemometric method of analysis leading to isolation of Fourier transform infrared (FT-IR) spectra of biomacromolecules (HEW lysozyme, ctDNA) affected by osmolytes (trimethylamine- N-oxide and N, N, N-trimethylglycine, respectively) in aqueous solutions. The method is based on the difference spectra method primarily used to characterize the structure of solvent affected by solute. The cyclical usage of factor analysis allows precise information to be obtained on the shape of “affected spectra” of analyzed biomacromolecules. “Affected spectra” of selected biomacromolecules give valuable information on their structure in the presence of the osmolytes in solution, as well as on the level of perturbation in dependence of osmolyte concentration. The method also gives a possibility of insight into the mechanism of interaction in presented types of systems. It can be easily adapted to various chemical and biochemical problems where vibrational or ultraviolet-visible (UV-Vis) spectroscopy is used.
Composition Analysis of Scattering Liquids Based on Spatially Offset Visible-Near-Infrared Spectroscopy
Authors: Xiong Chan , Li Gang , Lin Ling
Published: November 2012

Spatially offset visible–near-infrared (VIS-NIR) spectroscopy was used to analyze of chemical compositions of the scattering liquids in the visible and near-infrared region from 530 to 930 nm. An experimental setup was designed based on a supercontinuum white-light laser source, an electrically controlled translation stage, and a high-performance spectrometer. The spatially offset spectra of the scattering liquids (composed of diluted Intralipid® 20% in distilled water) were measured at 24 sequential positions in the radial distribution from the incident light. A partial least squares regression method was applied to obtain the Intralipid® concentration from the spatially offset spectra. The results showed that the prediction accuracy of the Intralipid® concentration obtained from the spectra collected at multiple sample points was better than that obtained from the spectra collected at a single sample point. The coefficient of determination in the prediction set is 0.9835 at the optimized number of sample points.
Single-Pulse Standoff Raman Detection of Chemicals from 120 m Distance during Daytime
Authors: Misra Anupam K. , Sharma Shiv K. , Acosta Tayro E. , Porter John N. , Bates David E.
Published: November 2012

The capability to analyze and detect the composition of distant samples (minerals, organics, and chemicals) in real time is of interest for various fields including detecting explosives, geological surveying, and pollution mapping. For the past 10 years, the University of Hawaii has been developing standoff Raman systems suitable for measuring Raman spectra of various chemicals in daytime or nighttime. In this article we present standoff Raman spectra of various minerals and chemicals obtained from a distance of 120 m using single laser pulse excitation during daytime. The standoff Raman system utilizes an 8-inch Meade telescope as collection optics and a frequency-doubled 532 nm Nd: YAG laser with pulse energy of 100 mJ/pulse and pulse width of 10 ns. A gated intensified charge-coupled device (ICCD) detector is used to measure time-resolved Raman spectra in daytime with detection time of 100 ns. A gate delay of 800 ns (equivalent to target placed at 120 m distance) was used to minimize interference from the atmospheric gases along the laser beam path and near-field scattering. Reproducible, good quality single-shot Raman spectra of various inorganic and organic chemicals and minerals such as ammonium nitrate, potassium perchlorate, sulfur, gypsum, calcite, benzene, nitrobenzene, etc., were obtained through sealed glass vials during daytime. The data indicate that various chemicals could easily be identified from their Raman fingerprint spectra from a far standoff distance in real time using single-shot laser excitation.