bluuebunny/crossref_metadata_2025 huggingface dataset:
β-conglycinin combined with fenofibrate or rosuvastatin have exerted distinct hypocholesterolemic effects in rats
Authors: Ferreira Ederlan S , Silva Maraiza A , Demonte Aureluce , Neves Valdir A
Published: January 2012

Background

There is increasing interest in non-pharmacological control of cholesterol and triglyceride levels in the plasma and diet-drug association represent an important area of studies. The objective of this study was to observe the hypocholesterolemic effect of soybean β-conglycinin (7S protein) alone and combined with fenofibrate and rosuvastatin, two hypolipidemic drugs.

Methods

The protein and drugs were administered orally once a day to rats and the effects were evaluated after 28 days. Wistar rats were divided into six groups (n = 9): hypercholesterolemic diet (HC), HC+7S protein (300 mg.kg-1 day-1) (HC-7S), HC+fenofibrate (30 mg.kg-1 day-1)(HC-FF), HC+rosuvastatin (10 mg.kg-1 day-1)(HC-RO), HC+7S+fenofibrate (HC-7S-FF) and HC+7S+rosuvastatin (HC-7S-RO).

Results

Animals in HC-7S, HC-FF and HC-RO exhibited reductions of 22.9, 35.8 and 18.8% in total plasma cholesterol, respectively. In HC-7S-FF, animals did not show significant alteration of the level in HC+FF while the group HC-7S-RO showed a negative effect in comparison with groups taking only protein (HC-7S) or drug (HC-RO). The administration of the protein, fenofibrate and rosuvastatin alone caused increases in the plasma HDL-C of the animals, while the protein-drug combinations led to an increase compared to HC-FF and HC-RO. The plasma concentration of triacylgycerides was significantly reduced in the groups without association, while HC-7S-FF showed no alteration and HC-7S-RO a little reduction.

Conclusion

The results of our study indicate that conglycinin has effects comparable to fenofibrate and rosuvastatin on the control of plasma cholesterol, HDL-C and triacylglycerides, when given to hypercholesterolemic rats, and suggests that the association of this protein with rosuvastatin alters the action of drug in the homeostasis of cholesterol.
Metal work-function-dependent barrier height of Ni contacts with metal-embedded nanoparticles to 4H-SiC
Authors: Kang Min-Seok , Ahn Jung-Joon , Moon Kyoung-Sook , Koo Sang-Mo
Published: January 2012

Metal, typically gold [Au], nanoparticles [NPs] embedded in a capping metal contact layer onto silicon carbide [SiC] are considered to have practical applications in changing the barrier height of the original contacts. Here, we demonstrate the use of silver [Ag] NPs to effectively lower the barrier height of the electrical contacts to 4H-SiC. It has been shown that the barrier height of the fabricated SiC diode structures (Ni with embedded Ag-NPs) has significantly reduced by 0.11 eV and 0.18 eV with respect to the samples with Au-NPs and the reference samples, respectively. The experimental results have also been compared with both an analytic model based on Tung's theory and physics-based two-dimensional numerical simulations.
Near optimal bound of orthogonal matching pursuit using restricted isometric constant
Authors: Wang Jian , Kwon Seokbeop , Shim Byonghyo
Published: January 2012

As a paradigm for reconstructing sparse signals using a set of under sampled measurements, compressed sensing has received much attention in recent years. In identifying the sufficient condition under which the perfect recovery of sparse signals is ensured, a property of the sensing matrix referred to as the restricted isometry property (RIP) is popularly employed. In this article, we propose the RIP based bound of the orthogonal matching pursuit (OMP) algorithm guaranteeing the exact reconstruction of sparse signals. Our proof is built on an observation that the general step of the OMP process is in essence the same as the initial step in the sense that the residual is considered as a new measurement preserving the sparsity level of an input vector. Our main conclusion is that if the restricted isometry constant δ

K
of the sensing matrix satisfies

δ

K

<

K
-
1

K
-
1
+
K

then the OMP algorithm can perfectly recover K(> 1)-sparse signals from measurements. We show that our bound is sharp and indeed close to the limit conjectured by Dai and Milenkovic.
Dual-task motor performance with a tongue-operated assistive technology compared with hand operations
Authors: Johnson Ashley N , Huo Xueliang , Ghovanloo Maysam , Shinohara Minoru
Published: January 2012

Background

To provide an alternative motor modality for control, navigation, and communication in individuals suffering from impairment or disability in hand functions, a Tongue Drive System (TDS) has been developed that allows for real time tracking of tongue motion in an unobtrusive, wireless, and wearable device that utilizes the magnetic field generated by a miniature disk shaped magnetic tracer attached to the tip of the tongue. The purpose of the study was to compare the influence of a concurrent motor or cognitive task on various aspects of simple movement control between hand and tongue using the TDS technology.

Methods

Thirteen young able-bodied adults performed rapid and slow goal-directed movements of hand and tongue (with TDS) with and without a concurrent motor (hand or tongue) or cognitive (arithmetic and memory) task. Changes in reaction time, completion time, speed, correctness, accuracy, variability of displacement, and variability of time due to the addition of a concurrent task were compared between hand and tongue.

Results

The influence of an additional concurrent task on motor performance was similar between the hand and tongue for slow movement in controlling their displacement. In rapid movement with a concurrent motor task, most aspects of motor performance were degraded in hand, while tongue speed during rapid continuous task was maintained. With a concurrent cognitive task, most aspects of motor performance were degraded in tongue, while hand accuracy during the rapid discrete task and hand speed during the rapid continuous task were maintained.

Conclusion

Rapid goal-directed hand and tongue movements were more consistently susceptible to interference from concurrent motor and cognitive tasks, respectively, compared with the other movement.
A novel study on amyloid β peptide 40, 42 and 40/42 ratio in Saudi autistics
Authors: Al-Ayadhi Laila Y , Ben Bacha Abir G , Kotb Malak , El-Ansary Afaf K
Published: January 2012

Objectives

We examined whether plasma concentrations of amyloid beta (Aβ) as protein derivatives play a central role in the etiology of autistic features.

Design and Methods

Concentrations of human Aβ (1-42), Aβ (1-40), and Aβ (40/42) in the plasma of 52 autistic children (aged 3-16 years) and 36 age-matched control subjects were determined by using the ELISA technique and were compared.

Results

Compared to control subjects, autistic children exhibited significantly lower concentrations of both Aβ (1-40) and Aβ (1-42) and lower Aβ (40/42) concentration ratio. Receiver operating characteristics curve (ROC) analysis showed that these measurements of Aβ peptides showed high specificity and sensitivity in distinguishing autistic children from control subjects.

Conclusions

Lower concentrations of Aβ (1-42) and Aβ (1-40) were attributed to loss of Aβ equilibrium between the brain and blood, an imbalance that may lead to failure to draw Aβ from the brain and/or impairment of β- and γ- secretase's concentration or kinetics as enzymes involving in Aβ production.
Precursor uptake assays and metabolic analyses in isolated tomato fruit chromoplasts
Authors: Angaman Djédoux Maxime , Petrizzo Rocco , Hernández-Gras Francesc , Romero-Segura Carmen , Pateraki Irene , Busquets Montserrat , Boronat Albert
Published: January 2012

Background

Carotenoids are the most widespread group of pigments found in nature. In addition to their role in the physiology of the plant, carotenoids also have nutritional relevance as their incorporation in the human diet provides health benefits. In non-photosynthetic tissues, carotenoids are synthesized and stored in specialized plastids called chromoplasts. At present very little is known about the origin of the metabolic precursors and cofactors required to sustain the high rate of carotenoid biosynthesis in these plastids. Recent proteomic data have revealed a number of biochemical and metabolic processes potentially operating in fruit chromoplasts. However, considering that chloroplast to chromoplast differentiation is a very rapid process during fruit ripening, there is the possibility that some of the proteins identified in the proteomic analysis could represent remnants no longer having a functional role in chromoplasts. Therefore, experimental validation is necessary to prove whether these predicted processes are actually operative in chromoplasts.

Results

A method has been established for high-yield purification of tomato fruit chromoplasts suitable for metabolic studies. Radiolabeled precursors were efficiently incorporated and further metabolized in isolated chromoplast. Analysis of labeled lipophilic compounds has revealed that lipid biosynthesis is a very efficient process in chromoplasts, while the relatively low incorporation levels found in carotenoids suggest that lipid production may represent a competing pathway for carotenoid biosynthesis. Malate and pyruvate are efficiently converted into acetyl-CoA, in agreement with the active operation of the malic enzyme and the pyruvate dehydrogenase complex in the chromoplast. Our results have also shown that isolated chromoplasts can actively sustain anabolic processes without the exogenous supply of ATP, thus suggesting that these organelles may generate this energetic cofactor in an autonomous way.

Conclusions

We have set up a method for high yield purification of intact tomato fruit chromoplasts suitable for precursor uptake assays and metabolic analyses. Using targeted radiolabeled precursors we have been able to unravel novel biochemical and metabolic aspects related with carotenoid and lipid biosynthesis in tomato fruit chromoplasts. The reported chromoplast system could represent a valuable platform to address the validation and characterization of functional processes predicted from recent transcriptomic and proteomic data.
Engineering better biomass-degrading ability into a GH11 xylanase using a directed evolution strategy
Authors: Song Letian , Siguier Béatrice , Dumon Claire , Bozonnet Sophie , O'Donohue Michael J
Published: January 2012

Background

Improving the hydrolytic performance of hemicellulases on lignocellulosic biomass is of considerable importance for second-generation biorefining. To address this problem, and also to gain greater understanding of structure-function relationships, especially related to xylanase action on complex biomass, we have implemented a combinatorial strategy to engineer the GH11 xylanase fromThermobacillus xylanilyticus(Tx-Xyn).

Results

Followingin vitroenzyme evolution and screening on wheat straw, nine best-performing clones were identified, which display mutations at positions 3, 6, 27 and 111. All of these mutants showed increased hydrolytic activity on wheat straw, and solubilized arabinoxylans that were not modified by the parental enzyme. The most active mutants, S27T and Y111T, increased the solubilization of arabinoxylans from depleted wheat straw 2.3-fold and 2.1-fold, respectively, in comparison to the wild-type enzyme. In addition, five mutants, S27T, Y111H, Y111S, Y111T and S27T-Y111H increased total hemicellulose conversion of intact wheat straw from 16.7%tot. xyl(wild-type Tx-Xyn) to 18.6% to 20.4%tot. xyl. Also, all five mutant enzymes exhibited a better ability to act in synergy with a cellulase cocktail (Accellerase 1500), thus procuring increases in overall wheat straw hydrolysis.

Conclusions

Analysis of the results allows us to hypothesize that the increased hydrolytic ability of the mutants is linked to (i) improved ligand binding in a putative secondary binding site, (ii) the diminution of surface hydrophobicity, and/or (iii) the modification of thumb flexibility, induced by mutations at position 111. Nevertheless, the relatively modest improvements that were observed also underline the fact that enzyme engineering alone cannot overcome the limits imposed by the complex organization of the plant cell wall and the lignin barrier.
Molecular prediction for atherogenic risks across different cell types of leukocytes
Authors: Cheng Feng , Keeley Ellen C , Lee Jae K
Published: January 2012

Background

Diagnosing subclinical atherosclerosis is often difficult since patients are asymptomatic. In order to alleviate this limitation, we have developed a molecular prediction technique for predicting patients with atherogenic risks using multi-gene expression biomarkers on leukocytes.

Methods

We first discovered 356 expression biomarkers which showed significant differential expression between genome-wide microarray data of monocytes from patients with familial hyperlipidemia and increased risk of atherosclerosis compared to normal controls. These biomarkers were further triaged with 56 biomarkers known to be directly related to atherogenic risks. We also applied a COXEN algorithm to identify concordantly expressed biomarkers between monocytes and each of three different cell types of leukocytes. We then developed a multi-gene predictor using all or three subsets of these 56 biomarkers on the monocyte patient data. These predictors were then applied to multiple independent patient sets from three cell types of leukocytes (macrophages, circulating T cells, or whole white blood cells) to predict patients with atherogenic risks.

Results

When the 56 predictor was applied to the three patient sets from different cell types of leukocytes, all significantly stratified patients with atherogenic risks from healthy people in these independent cohorts. Concordantly expressed biomarkers identified by the COXEN algorithm provided slightly better prediction results.

Conclusion

These results demonstrated the potential of molecular prediction of atherogenic risks across different cell types of leukocytes.
Nasopharyngeal carriage rate of Streptococcus pneumoniae in Ugandan children with sickle cell disease
Authors: Kateete David P , Kajumbula Henry , Kaddu-Mulindwa Deogratias H , Ssevviri Augustine K
Published: January 2012

Background

Nasopharyngeal carriage ofStreptococcus pneumoniaeis a determinant for invasive pneumococcal disease, which often complicates homozygous sickle cell disease. Here, we determined the nasopharyngeal carriage rate ofS. pneumoniaein Ugandan children with homozygous sickle cell disease, who attended the outpatient Sickle Cell Clinic at Mulago National Referral hospital in Kampala, Uganda.

Results

S. pneumoniaeoccurred in 27 of the 81 children with homozygous sickle cell disease (giving a carriage rate of 33%, 27/81). Twenty three children were previously hospitalized of whomS. pneumoniaeoccurred in only two (9%, 2/23), while among the 58 who were not previously hospitalized it occurred in 25 (43%, 25/58, χ2= 8.8,p= 0.003), meaning there is an association between high carriage rate and no hospitalization. Two children previously immunized with the pneumococcal conjugate vaccine did not carry the organism. Prior antimicrobial usage was reported in 53 children (65%, 53/81). There was high resistance of pneumococci to penicillin (100%, 27/27) and trimethoprime-sulfamethoxazole (97%, 26/27), but low resistance to other antimicrobials. Of the 70 children without sickle cell disease,S. pneumoniaeoccurred in 38 (54%, 38/70) of whom 43 were males and 27 females (53% males, 23/43, and 56% females, 15/27).

Conclusion

Nasopharyngeal carriage of penicillin resistant pneumococci in Ugandan children with homozygous sickle cell disease is high. While nasopharyngeal carriage ofS. pneumoniaeis a determinant for invasive pneumococcal disease, pneumococcal bacteremia is reportedly low in Ugandan children with sickle cell disease. Studies on the contribution of high carriage rates to invasive pneumococcal disease in these children will be helpful. This is the first report on pneumococcal carriage rate in Ugandan children with sickle cell disease.
Sialoglycoproteins adsorbed byPseudomonas aeruginosafacilitate their survival by impeding neutrophil extracellular trap through siglec-9
Authors: Khatua Biswajit , Bhattacharya Kaushik , Mandal Chitra
Published: January 2012

PA is an opportunistic pathogen that is commonly associated with severe infection in immunocompromised hosts. Siglec-9 binds with Sias by cis interaction on the neutrophil surface, thereby reducing immunological activity. However, neutrophils bind with pathogens through trans interactions of siglec-9 with Sias. Neutrophils kill invading pathogens by NETs, along with extracellular phagocytosis. Here, we report the mode of the adsorption of Sias by PA from host serum, the interaction of PA+Sias with human neutrophils, and the resulting neutrophil immunological activity. The α2–3-linked sialoglycoproteins adsorbed by PA exhibited potent binding with the soluble siglec-9-Fc chimeras, CHO-siglec-9 and siglec-9 on neutrophils. The binding between PA+Sias and neutrophils was blocked by the synthetic sialoglycan Neu5Acα2–3Galβ1–4GlcNAc, confirming the linkage-specific, Sias–siglec-9 interaction. The PA+Sias and siglec-9 interaction on neutrophils reduced the level of ROS and the release of elastase, resulting in a reduction of NETs formation, demonstrating the role of the sialoglycoproteins adsorbed by PA in the weakening of neutrophil activity. The resistance of PA+Sias to NETs was made evident by the increased survival of PA+Sias. Moreover, the decrease in PA−Sias survival demonstrated the involvement of NETs formation in the absence of the Sias–siglec-9 interaction. N-actylcysteine or sivelestat-pretreated neutrophils enhanced the survival of PA−Sias. DNAse-pretreated neutrophils did not exhibit any NETs formation, resulting in the enhanced escape of PA−Sias. Taken together, one of the survival mechanisms of PA+Sias is the diminution of innate immunity via its adsorption of sialoglycoproteins by its engagement of the inhibitory molecule siglec-9. This is possibly a general mechanism for pathogens that cannot synthesize Sias to subvert immunity.
Deletion of CaMKK2 from the Liver Lowers Blood Glucose and Improves Whole-Body Glucose Tolerance in the Mouse
Authors: Anderson Kristin A. , Lin Fumin , Ribar Thomas J. , Stevens Robert D. , Muehlbauer Michael J. , Newgard Christopher B. , Means Anthony R.
Published: January 2012

Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a member of the Ca2+/CaM-dependent protein kinase family that is expressed abundantly in brain. Previous work has revealed that CaMKK2 knockout (CaMKK2 KO) mice eat less due to a central nervous system -signaling defect and are protected from diet-induced obesity, glucose intolerance, and insulin resistance. However, here we show that pair feeding of wild-type mice to match food consumption of CAMKK2 mice slows weight gain but fails to protect from diet-induced glucose intolerance, suggesting that other alterations in CaMKK2 KO mice are responsible for their improved glucose metabolism. CaMKK2 is shown to be expressed in liver and acute, specific reduction of the kinase in the liver of high-fat diet-fed CaMKK2floxed mice results in lowered blood glucose and improved glucose tolerance. Primary hepatocytes isolated from CaMKK2 KO mice produce less glucose and have decreased mRNA encoding peroxisome proliferator-activated receptor γ coactivator 1-α and the gluconeogenic enzymes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, and these mRNA fail to respond specifically to the stimulatory effect of catecholamine in a cell-autonomous manner. The mechanism responsible for suppressed gene induction in CaMKK2 KO hepatocytes may involve diminished phosphorylation of histone deacetylase 5, an event necessary in some contexts for derepression of the peroxisome proliferator-activated receptor γ coactivator 1-α promoter. Hepatocytes from CaMKK2 KO mice also show increased rates of de novo lipogenesis and fat oxidation. The changes in fat metabolism observed correlate with steatotic liver and altered acyl carnitine metabolomic profiles in CaMKK2 KO mice. Collectively, these results are consistent with suppressed catecholamine-induced induction of gluconeogenic gene expression in CaMKK2 KO mice that leads to improved whole-body glucose homeostasis despite the presence of increased hepatic fat content.
“Intolerable Subjects”
Authors: Grinnell Lucinda
Published: January 2012

In 1982, responding to the worldwide economic crisis and an elevated national debt, Mexico enacted neoliberal reforms and sought to increase social control through stricter penal codes. While penal codes in Mexico City had criminalized violations of “public morality” for many years and there was a history of policing “sexual deviants” on the basis of such accusations, the discourse of “moral renovation” inadvertently opened the door for gay and lesbian activists to create counterdiscourses and participate in transnational countermovements. In both their pronouncements to the national public and requests for international solidarity, Mexican activists clearly connected the politics of austerity to the politics of morality and encouraged international actors to condemn repression and support broad-based human rights in Mexico. This essay examines the politics of “moral renovation” as it related to neoliberal economics and analyzes the varying strategies that lesbian and gay activists used in order to negotiate these social, political, and economic realities.
Neoliberal Captivities
Authors: Spira Tamara Lea
Published: January 2012

This article treats Pisagua prison in northern Chile, which intermittently served as a concentration camp for leftists and queer “sexual dissidents” throughout the twentieth century and was converted into a hotel after the transition to democracy in 1990. It proposes a theoretical formulation of neoliberal captivities, which the author defines as the process through which programs of counterrevolutionary backlash and war making become encrypted into neoliberal definitions of “peace” and “freedom,” and violence becomes subsumed into normative structures of daily life. The author's argument is twofold. First, she argues that Pisagua functions as a salient example of the shift between formal and informal modes of counterrevolutionary warfare — articulating a logic she characterizes as “low-intensity warfare” that has been central to the attempt to shore up hegemony in the wake of broader revolutionary upsurges of the 1960s and 1970s. Secondly, she argues that Pisagua reveals many of the unresolved contradictions — in particular, the deeper and yet-to-be-resolved gendered, racialized, sexualized, and classed contradictions endemic to capitalist modernity and nation building — that the neoliberal form attempts to mask. Placing Pisagua within a longer durée of struggle, the article scours the deep and multilayered histories of class, gender, racial, and imperial violence that take form within Pisagua — all of which are ironically neutralized through the figure of its torture-center-turned-hotel. In so doing, the author aims to reach beneath neoliberalism's sleek veneer and “low-intensity” forms — lending ultimately to a genealogy of struggle for radical justice that does not cede to neoliberalism's thwarting operations.
Imaginative Militancy and the Transnational Poetry Dialogue
Authors: Nowak Mark
Published: January 2012

This essay examines how small-scale projects grounded in imaginative militancy and transformatory global forms of solidarity can move workers from low levels of solidarity toward more radical levels. It focuses on a series of creative writing workshops facilitated by the author which brought workers at Ford plants in St. Paul, Minnesota, and Port Elizabeth and Pretoria, South Africa, into productive transnational “poetry dialogues.” It contends that while the dialogues raised workers' identity as workers to an international scale, their effects were limited due to a single industry focus and a reactive rather than productive stance. The essay concludes by arguing that small-scale projects grounded in imaginative militancy can serve an important role in contemporary labor education.
Old Elites in a New Republic: The Reconversion of Ottoman Bureaucratic Families in Turkey (1909–1939)
Authors: Bouquet Olivier
Published: January 2012

The Kemalist officers who set up the new regime in the aftermath of the Turkish national struggle for independence (1919–22) officially declared against the prominent senior dignitaries who had served the Ottoman imperial state. However, far from deeming it necessary to destroy a complete segment of the society as a prerequisite for establishing full control over the masses, the republican leaders pragmatically vested old families with the right to explore their competences and make use of their abilities. As far as the imperial state had been unchallenged in supervising the ongoing changes affecting the organization of socioprofessional activities, that is, the emergence of journalists, lawyers, or academics as elite segments, not only did old established families use their positions to organize their reconversion at the margins of the classical administrative sphere, but they were also promoted through the new official apparatus as diplomats, professors, and even politicians. Interestingly enough, the republican regime associated two apparent oppositions: declared antipathy toward Ottoman bureaucratic elites and the effective use of their heirs both as a way to organize the state.
Calligraphy and the Art of Statecraft in the Late Ottoman Empire and Modern Turkish Republic
Authors: Griffith Zoe
Published: January 2012

State building and nationalism have been widely examined in the context of both the late Ottoman Empire and the modern Turkish Republic. This article explores the role of Islamic calligraphy and calligraphers during the final decades of Ottoman rule and through the twentieth century in terms of their contribution, both materially and ideologically, to the development of national identity in Turkey. Because calligraphy in Turkey has always enjoyed a unique relationship with Islam, it has been impossible to fully separate the art from the Ottoman-Islamic past. Having survived the transition in modern Turkey from the Arabic to the Latin script, calligraphy thus serves as an alternative, and perhaps subtly oppositional, form of expression in the Turkish Republic. That Islamic calligraphy continues to be appreciated in Turkey demonstrates resistance to the national identity handed down by Kemalists in an attempt to erase Islam and the Turks’ immediate Ottoman past since the 1920s.
The Circuitous Origins of the Gender Perspective in Human Rights Advocacy: A Challenge for Transnational Feminisms
Authors: Quataert Jean H.
Published: January 2012

This article pieces together a complex genealogy of the multiple contexts that helped reshape women’s international organizing and create a global women’s human rights movement following the United Nations (UN) Decade for Women, 1975–85. It maps a multilayered history consisting of many different strands of women’s activities around the globe that increasingly converged in the 1970s, although in unanticipated ways. Through its broad focus on women in distinct social, political, and intellectual arenas, it links the UN human rights system and its oversight committees and commissions with the first two UN Development Decades of the 1960s and 1970s. And it interconnects these global structures, discourses, and activities with old and new patterns of women’s postwar organizing and with the emerging challenges to canons of knowledge and research methodologies from feminist theory and epistemology. Starting in the mid-1970s, four distinct yet overlapping endeavors converged: the work for international human rights, colonial and postcolonial expectations of economic development and well-being, women’s rights and liberation movements, and women’s studies in their global translations. This critical history, however, has all but been lost in the fraught contemporary debates about human rights as a vehicle for radical gender and social change.
The epigenetic H3S10 phosphorylation mark is required for counteracting heterochromatic spreading and gene silencing inDrosophila melanogaster
Authors: Wang Chao , Cai Weili , Li Yeran , Deng Huai , Bao Xiaomin , Girton Jack , Johansen Jørgen , Johansen Kristen M.
Published: January 2012

The JIL-1 kinase localizes specifically to euchromatin interband regions of polytene chromosomes and is the kinase responsible for histone H3S10 phosphorylation at interphase. Genetic interaction assays with strong JIL-1 hypomorphic loss-of-function alleles have demonstrated that the JIL-1 protein can counterbalance the effect of the major heterochromatin components on position-effect variegation (PEV) and gene silencing. However, it is unclear whether this was a causative effect of the epigenetic H3S10 phosphorylation mark, or whether the effect of the JIL-1 protein on PEV was in fact caused by other functions or structural features of the protein. By transgenically expressing various truncated versions of JIL-1, with or without kinase activity, and assessing their effect on PEV and heterochromatic spreading, we show that the gross perturbation of polytene chromosome morphology observed in JIL-1 null mutants is unrelated to gene silencing in PEV and is likely to occur as a result of faulty polytene chromosome alignment and/or organization, separate from epigenetic regulation of chromatin structure. Furthermore, the findings provide evidence that the epigenetic H3S10 phosphorylation mark itself is necessary for preventing the observed heterochromatic spreading independently of any structural contributions from the JIL-1 protein.
Candidate Serum Biomarkers for Prostate Adenocarcinoma Identified by mRNA Differences in Prostate Tissue and Verified with Protein Measurements in Tissue and Blood
Authors: Klee Eric W , Bondar Olga P , Goodmanson Marcia K , Dyer Roy B , Erdogan Sibel , Bergstralh Eric J , Bergen H. Robert , Sebo Thomas J , Klee George G
Published: January 2012

BACKGROUND

Improved tests are needed for detection and management of prostate cancer. We hypothesized that differential gene expression in prostate tissue could help identify candidate blood biomarkers for prostate cancer and that blood from men with advanced prostate disease could be used to verify the biomarkers presence in circulation.

METHODS

We identified candidate markers using mRNA expression patterns from laser-capture microdissected prostate tissue and confirmed tissue expression using immunohistochemistry (IHC) for the subset of candidates having commercial antisera. We analyzed tissue extracts with tandem mass spectrometry (MS/MS) and measured blood concentrations using immunoassays and MS/MS of trypsin-digested, immunoextracted peptides.

RESULTS

We selected 35 novel candidate prostate adenocarcinoma biomarkers. For all 13 markers having commercial antisera for IHC, tissue expression was confirmed; 6 showed statistical discrimination between nondiseased and malignant tissue, and only 5 were detected in tissue extracts by MS/MS. Sixteen of the 35 candidate markers were successfully assayed in blood. Four of 8 biomarkers measured by ELISA and 3 of 10 measured by targeted MS showed statistically significant increases in blood concentrations of advanced prostate cancer cases, compared with controls.

CONCLUSIONS

Seven novel biomarkers identified by gene expression profiles in prostate tissue were shown to have statistically significant increased concentrations in blood from men with advanced prostate adenocarcinoma compared with controls: apolipoprotein C1, asporin, cartilage oligomeric matrix protein, chemokine (C-X-C motif) ligand 11 (CXCL11), CXCL9, coagulation factor V, and proprotein convertase subtilisin/kexin 6.
Timothy Snyders „Bloodlands"
Authors: Zarusky Jürgen
Published: January 2012

Vorspann

Eine „Reise ins Herz der Finsternis“ verheißt der Klappentext der deutschen Ausgabe von Timothy Snyders aufsehenerregendem Buch „Bloodlands“. Es geht darin um die Geschichte jener Gebiete Ost und Ostmitteleuropas, die nacheinander von den Massenverbrechen der Regime Stalins und Hitlers betroffen waren. Jürgen Zarusky, Historiker am Institut für Zeitgeschichte, hat sich mit dem Buch eingehend auseinandergesetzt und kommt zu einer kritischen Einschätzung: Die „Bloodlands“ sind keine historische Landschaft, sondern ein Konstrukt, in dem geschichtliche Zusammenhänge teils zerschnitten, teils künstlich hergestellt werden. Stalinismus und Nationalsozialismus erscheinen dabei ähnlicher als sie es tatsächlich waren.
Ordentliche Beschäftigungspolitik?
Authors: Humann Detlev
Published: January 2012

Vorspann

Die Überwindung der Massenarbeitslosigkeit gilt noch immer als ein Erfolg des NS-Regimes. Die bloßen Zahlen belegen, dass es dem Regime bis 1939 gelang, für Vollbeschäftigung zu sorgen. Zu welchen Methoden die Nationalsozialisten dabei jahrelang griffen, ist bislang häufig übersehen worden. Eine Diktatur wie die nationalsozialistische schreckte nicht davor zurück, mit zum Teil außerordentlich rüden Methoden die Arbeitslosen „von der Straße zu bringen“ und so die offiziellen Statistiken zu schönen.
Leben nach dem GULAG
Authors: Sprau Mirjam
Published: January 2012

Vorspann

Nach Stalins Tod begann sich der GULAG zu leeren. Die ehemaligen Häftlinge atmeten auf, gingen aber in vielen Fällen auch dann einer ungewissen Zukunft entgegen, wenn sie selbst nach sowjetischen Maßstäben gänzlich unschuldig in das Räderwerk der Verfolgung geraten waren. Ohne Arbeit, ohne Wohnung, ohne Rehabilitierungschance blieben sie häufig am Rande der sowjetischen Gesellschaft, und ein Objekt der Willkür der kommunistischen Partei, wie Mirjam Sprau unter Rückgriff auf zahlreiche Petitionen beispielhaft und plastisch zu zeigen vermag. Bessere Rehabilitierungs- und damit persönliche Konsolidierungschancen hatten nur Angehörige der Parteielite, die nach der Haft ihre alten Beziehungen reaktivieren konnten.
Der Kreml und die Friedensbewegung Anfang der achtziger Jahre
Authors: Wettig Gerhard
Published: January 2012

Vorspann

Aus sowjetischer Sicht war, wie die internen Quellen und auch die faktische Politik belegen, die westliche Friedensbewegung ein äußerst wichtiger Faktor im Ost-West-Konflikt. Dieser Gesichtspunkt bestimmte das Verhältnis zu ihr. Die Frage, inwieweit die UdSSR diese Bewegung für ihre Zwecke einzusetzen vermochte, lässt sich nicht mit dem Hinweis beantworten, dass die Mehrzahl der daran Beteiligten anderen Vorstellungen folgte als der Kreml. Entscheidend ist vielmehr, wie weit sich diese Bewegung – auch entgegen den eigenen Absichten - von der Sowjetunion politisch vereinnahmen ließ und damit deren Ziele gegen die NATO faktisch unterstützte, auch wenn das ihrer Gesinnung eigentlich nicht entsprach.
Private Practices
Authors: Schlueter John P.
Published: January 2012

This essay uses selected works of Washington Irving and Ralph Waldo Emerson to delineate two different privacies. The first privacy is associated with secreted spaces, whether physical or personal, and is one that has been normalized. The other privacy is under-appreciated and far less understood: it is an unpredictable, speculative flight of what Irving calls “fancy.” The essay argues that each privacy comes with a distinct set of consequences. If we choose to associate privacy with secreted spaces, we ourselves become like texts, able to be read, and we then associate with others as if they can be read as well. If our privacy is “fanciful,” in contrast, we balance the pleasures of being alone with those of being with others. In the end, the essay hopes to dissociate privacy (or a version of it) from privation, and to offer it as a positive, cultural concept. In doing so, it aligns itself with recent explorations of privacy in the context of nineteenth-century American literature.
PTHrP-associated hypercalcemia of pregnancy resolved after delivery: a case report
Authors: Eller-Vainicher Cristina , Ossola Manuela Wally , Beck-Peccoz Paolo , Chiodini Iacopo
Published: January 2012

A 35-year-old oriental woman, who was 32 weeks pregnant, was hospitalized with suspected preeclampsia. Subsequently, she developed stupor and lethargia. Biochemical assessment showed severe hypercalcemia (21 mg/dl) with undetectable parathyroid hormone (PTH) and markedly elevated PTH-related peptide (PTHrP) levels (26 pmol/l, normal values <1.1 pmol/l). The patient was treated with i.v. fluid administration, which resulted in an unsatisfactory reduction in serum calcium. Therefore, a cesarean section was performed to deliver the baby. Serum calcium levels promptly normalized after delivery with undetectable PTHrP levels. She delivered a healthy infant only presenting with transient mild jaundice and slightly prolonged QT interval with serum calcium level of 7.8–8.4 mg/dl (corrected for albumin levels). In the subsequent days, the patient developed a transient ‘hungry bone’ syndrome (calcium 6.7 mg/dl, phosphorous 2.1 mg/dl, and PTH 100.4 pg/ml). In conclusion, this pregnant patient presented with PTHrP-associated hypercalcemia, presumably of placental origin. Delivery resulted in prompt reduction of serum calcium levels and a transient ‘hungry bone’ syndrome.
Recognizing menopause in women with amenorrhea induced by cytotoxic chemotherapy for endocrine-responsive early breast cancer
Authors: Torino Francesco , Barnabei Agnese , De Vecchis Liana , Appetecchia Marialuisa , Strigari Lidia , Corsello Salvatore M
Published: January 2012

Cytotoxic anticancer treatment may induce amenorrhea or menopause to a variable extent. These side effects may not only impair or impede fertility but also cause sexual dysfunction, bone loss, and menopausal symptoms, with a strikingly negative effect on quality of life in many women. Aromatase inhibitors (AIs) are a recommended adjuvant endocrine treatment option in postmenopausal patients affected by early breast cancer (EBC) but are contraindicated in premenopausal women and in those with residual ovarian function. Women over 40 years of age with chemotherapy-induced amenorrhea (CIA) and routine hormonal levels consistent with menopause may receive an AI as adjuvant endocrine treatment. For these women, the tools available to identify menopause do not appear to be completely reliable. This review focused on the pathophysiology of ovarian toxicity induced by cytotoxic agents and on potentially useful methods to diagnose chemotherapy-induced menopause in patients treated with adjuvant chemotherapy for endocrine-responsive EBC. Moreover, practical approaches are proposed to distinguish true menopausal women, who would benefit from AIs, from those with transient or persistent CIA.
Activation of the Sonic Hedgehog pathway in thyroid neoplasms and its potential role in tumor cell proliferation
Authors: Xu Xiulong , Ding Helen , Rao Geetha , Arora Shalini , Saclarides Constantine P , Esparaz Joseph , Gattuso Paolo , Solorzano Carmen C , Prinz Richard A
Published: January 2012

The sonic hedgehog (SHH) pathway is activated in several types of malignancy and plays an important role in tumor cell proliferation and tumorigenesis. SHH binding to a 12-pass transmembrane receptor, Patched (PTCH), leads to freeing of Smoothened (SMO) and subsequent activation of GLI transcription factors. In the present study, we analyzed the expression of SHH, PTCH, SMO, and GLI1 in 31 follicular thyroid adenomas (FTA), 8 anaplastic thyroid carcinomas (ATC), and 51 papillary thyroid carcinomas (PTC) by immunohistochemical staining. More than 65% of FTA, PTC, and ATC specimens stained positive for SHH, PTCH, SMO, and GLI. However, the expression of the genes encoding these four molecules did not correlate with any clinicopathologic parameters, including the age, gender, the status ofBRAFgene mutation, tumor stage, local invasion, and metastasis. Three thyroid tumor cell lines (KAT-18, WRO82, and SW1736) all expressed the genes encoding these four molecules. 5-Bromo-2-deoxyuridine labeling and MTT cell proliferation assays revealed that cyclopamine (CP), an inhibitor of the SHH pathway, was able to inhibit the proliferation of KAT-18 and WRO82 cells more effectively than SW1736 cells. CP led to the arrest of cell cycle or apoptosis. Knockdown ofSHHandGLIexpression by miRNA constructs that targetSHHorGLImRNA in KAT-18 and SW1736 cells led to the inhibition of cell proliferation. Our results suggest that the SHH pathway is widely activated in thyroid neoplasms and may have potential as an early marker of thyroid cancer or as a potential therapeutic target for thyroid cancer treatment.
Applying new clinicopathological characteristics to prognostication in advanced thyroid carcinoma
Authors: Cabanillas Maria E , Sherman Steven I
Published: January 2012

In the February 2011 issue of Endocrine-Related Cancer, Deandreis et al. reported that increased FDG uptake was prognostic in patients with metastatic thyroid cancer. Fludeoxyglucose-positron emission tomography (FDG-PET) is routinely used in the staging and follow-up of patients with cancer. This study gives further evidence for the role of FDG-PET scanning in metastatic thyroid cancer, especially to identify patients with aggressive disease requiring systemic therapy.
Neoplasms Associated with Germline and Somatic NF1 Gene Mutations
Authors: Patil Sachin , Chamberlain Ronald S.
Published: January 2012

Learning Objectives

After completing this course, the reader will be able to: Describe phenotypic and clinical features associated with neurofibromatosis 1.Identify malignant tumors associated with neurofibromatosis 1.

This article is available for continuing medical education credit at CME.TheOncologist.com

Introduction.

Neurofibromatosis 1 is a tumor predisposition genetic syndrome with autosomal dominant inheritance and virtually 100% penetrance by the age of 5 years. NF1 results from a loss-of-function mutation in the NF1 gene, resulting in decreased levels of neurofibromin in the cell. Neurofibromin is a negative regulator of various intracellular signaling pathways involved in the cellular proliferation. Although the loss of heterozygosity in the NF1 gene may predispose NF1 patients to certain malignancies, additional genetic alterations are a prerequisite for their development. The precise nature of these additional genetic alterations is not well defined, and genetic testing of all malignancies in NF1 patients becomes an essential component of future research in this subset of patients. In addition to germline NF1 mutations, alteration of the somatic NF1 gene is associated with sporadic malignancies such as adenocarcinoma of the colon, myelodysplastic syndrome, and anaplastic astrocytoma.

Materials and Methods.

A comprehensive English and non-English language search for all articles pertinent to malignancies associated with NF1 was conducted using PubMed, a search engine provided by the U.S. National Library of Medicine and the National Institutes of Health. Key words searched included the following: “malignancies associated with NF1”, “tumors associated with NF1”, and “NF1 and malignancies”. A comprehensive analysis in terms age and mode of presentation, investigation and therapeutic modalities, and outcome of the published data was performed and compared with similar information on the sporadic cases.

Results.

Malignancies in NF1 patients typically occur at an earlier age and, with an exception of optic pathway gliomas, certain types of malignancies carry a poor prognosis compared with their sporadic counterparts. Malignancies are the leading cause of death in NF1 patients, resulting in a 10- to 15-year decreased life expectancy compared with the general population.

Conclusions.

The lack of well-defined screening tests for early detection and the nonspecific clinical presentation contributes to a poorer outcome in malignancies associated with NF1. Small study group size, mixed patient population, and a lack of uniformity in reporting research results make comparison of treatment outcome for this group difficult. An International Consensus Meeting to address and recommend best practices for screening, diagnosis, management, and follow-up of malignancies associated with NF1 is needed.
Habitat selection predicts genetic relatedness in an alpine ungulate
Authors: Shafer Aaron B. A. , Northrup Joseph M. , White Kevin S. , Boyce Mark S. , Côté Steeve D. , Coltman David W.
Published: January 2012

Landscape heterogeneity plays an integral role in shaping ecological and evolutionary processes. Despite links between the two disciplines, ecologists and population geneticists have taken different approaches to evaluating habitat selection, animal movement, and gene flow across the landscape. Ecologists commonly use statistical models such as resource selection functions (RSFs) to identify habitat features disproportionately selected by animals, whereas population genetic approaches model genetic differentiation according to the distribution of habitat variables. We combined ecological and genetic approaches by using RSFs to predict genetic relatedness across a heterogeneous landscape. We constructed sex‐ and season‐specific resistance surfaces based on RSFs estimated using data from 102 GPS (global positioning system) radio‐collared mountain goats (Oreamnos americanus) in southeast Alaska, USA. Based on mountain goat ecology, we hypothesized that summer and male surfaces would be the best predictors of relatedness. All individuals were genotyped at 22 microsatellite loci, which we used to estimate genetic relatedness. Summer resistance surfaces derived from RSFs were the best predictors of genetic relatedness, and winter models the poorest. Mountain goats generally selected for areas close to escape terrain and with a high heat load (a metric related to vegetative productivity and snow depth), while avoiding valleys. Male‐ and female‐specific surfaces were similar, except for winter, for which male habitat selection better predicted genetic relatedness. The null models of isolation‐by‐distance and barrier only outperformed the winter models. This study merges high‐resolution individual locations through GPS telemetry and genetic data, that can be used to validate and parameterize landscape genetics models, and further elucidates the relationship between landscape heterogeneity and genetic differentiation.
Neighborhood effects on seed dispersal by frugivores: testing theory with a mistletoe–marsupial system in Patagonia
Authors: Morales Juan Manuel , Rivarola María Daniela , Amico Guillermo , Carlo Tomás A.
Published: January 2012

The outcome of the dispersal process in zoochorous plants is largely determined by the behavior of frugivorous animals. Recent simulation studies have found that fruit removal rates and mean dispersal distances are strongly affected by fruiting plant neighborhoods. We empirically tested the effects of conspecific fruiting plant neighborhoods, crop sizes, and plant accessibility on fruit removal rates and seed dispersal distances of a mistletoe species exclusively dispersed by an arboreal marsupial in Northern Patagonia. Moreover, in this study, we overcome technical limitations in the empirical estimation of seed dispersal by using a novel 15N stable isotope enrichment technique together with Bayesian mixing models that allowed us to identify dispersed seeds from focal plants without the need of extensive genotyping. We found that, as predicted by theory, plants in denser neighborhoods had greater fruit removal and shorter mean dispersal distances than more isolated plants. Furthermore, the probability of dispersing seeds farther away decreased with neighborhood density. Larger crop sizes resulted in larger fruit removal rates and smaller probabilities of longer distance dispersal. The interplay between frugivore behavioral decisions and the spatial distribution of plants could have important consequences for plant spatial dynamics.