bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the benefits of using mate-pairs to resolve repeats in de novo short-read prokaryotic assemblies
Authors: Wetzel Joshua , Kingsford Carl , Pop Mihai
Published: April 2011

Background

Next-generation sequencing technologies allow genomes to be sequenced more quickly and less expensively than ever before. However, as sequencing technology has improved, the difficulty of de novo genome assembly has increased, due in large part to the shorter reads generated by the new technologies. The use of mated sequences (referred to as mate-pairs) is a standard means of disambiguating assemblies to obtain a more complete picture of the genome without resorting to manual finishing. Here, we examine the effectiveness of mate-pair information in resolving repeated sequences in the DNA (a paramount issue to overcome). While it has been empirically accepted that mate-pairs improve assemblies, and a variety of assemblers use mate-pairs in the context of repeat resolution, the effectiveness of mate-pairs in this context has not been systematically evaluated in previous literature.

Results

We show that, in high-coverage prokaryotic assemblies, libraries of short mate-pairs (about 4-6 times the read-length) more effectively disambiguate repeat regions than the libraries that are commonly constructed in current genome projects. We also demonstrate that the best assemblies can be obtained by 'tuning' mate-pair libraries to accommodate the specific repeat structure of the genome being assembled - information that can be obtained through an initial assembly using unpaired reads. These results are shown across 360 simulations on 'ideal' prokaryotic data as well as assembly of 8 bacterial genomes using SOAPdenovo. The simulation results provide an upper-bound on the potential value of mate-pairs for resolving repeated sequences in real prokaryotic data sets. The assembly results show that our method of tuning mate-pairs exploits fundamental properties of these genomes, leading to better assemblies even when using an off -the-shelf assembler in the presence of base-call errors.

Conclusions

Our results demonstrate that dramatic improvements in prokaryotic genome assembly quality can be achieved by tuning mate-pair sizes to the actual repeat structure of a genome, suggesting the possible need to change the way sequencing projects are designed. We propose that a two-tiered approach - first generate an assembly of the genome with unpaired reads in order to evaluate the repeat structure of the genome; then generate the mate-pair libraries that provide most information towards the resolution of repeats in the genome being assembled - is not only possible, but likely also more cost-effective as it will significantly reduce downstream manual finishing costs. In future work we intend to address the question of whether this result can be extended to larger eukaryotic genomes, where repeat structure can be quite different.
Support for the reproductive ground plan hypothesis of social evolution and major QTL for ovary traits of Africanized worker honey bees (Apis melliferaL.)
Authors: Graham Allie M , Munday Michael D , Kaftanoglu Osman , Page Robert E , Amdam Gro V , Rueppell Olav
Published: April 2011

Background

The reproductive ground plan hypothesis of social evolution suggests that reproductive controls of a solitary ancestor have been co-opted during social evolution, facilitating the division of labor among social insect workers. Despite substantial empirical support, the generality of this hypothesis is not universally accepted. Thus, we investigated the prediction of particular genes with pleiotropic effects on ovarian traits and social behavior in worker honey bees as a stringent test of the reproductive ground plan hypothesis. We complemented these tests with a comprehensive genome scan for additional quantitative trait loci (QTL) to gain a better understanding of the genetic architecture of the ovary size of honey bee workers, a morphological trait that is significant for understanding social insect caste evolution and general insect biology.

Results

Back-crossing hybrid European x Africanized honey bee queens to the Africanized parent colony generated two study populations with extraordinarily large worker ovaries. Despite the transgressive ovary phenotypes, several previously mapped QTL for social foraging behavior demonstrated ovary size effects, confirming the prediction of pleiotropic genetic effects on reproductive traits and social behavior. One major QTL for ovary size was detected in each backcross, along with several smaller effects and two QTL for ovary asymmetry. One of the main ovary size QTL coincided with a major QTL for ovary activation, explaining 3/4 of the phenotypic variance, although no simple positive correlation between ovary size and activation was observed.

Conclusions

Our results provide strong support for the reproductive ground plan hypothesis of evolution in study populations that are independent of the genetic stocks that originally led to the formulation of this hypothesis. As predicted, worker ovary size is genetically linked to multiple correlated traits of the complex division of labor in worker honey bees, known as the pollen hoarding syndrome. The genetic architecture of worker ovary size presumably consists of a combination of trait-specific loci and general regulators that affect the whole behavioral syndrome and may even play a role in caste determination. Several promising candidate genes in the QTL intervals await further study to clarify their potential role in social insect evolution and the regulation of insect fertility in general.
Detection and function of an intramolecular disulfide bond in the pH-responsive CadC of Escherichia coli
Authors: Tetsch Larissa , Koller Christiane , Dönhöfer Alexandra , Jung Kirsten
Published: April 2011

Background

In an acidic and lysine-rich environmentEscherichia coliinduces expression of thecadBAoperon which encodes CadA, the lysine decarboxylase, and CadB, the lysine/cadaverine antiporter.cadBAexpression is dependent on CadC, a membrane-integrated transcriptional activator which belongs to the ToxR-like protein family. Activation of CadC requires two stimuli, lysine and low pH. Whereas lysine is detected by an interplay between CadC and the lysine-specific transporter LysP, pH alterations are sensed by CadC directly. Crystal structural analyses revealed a close proximity between two periplasmic cysteines, Cys208 and Cys272.

Results

Substitution of Cys208 and/or Cys272 by alanine resulted in CadC derivatives that were active in response to only one stimulus, either lysine or pH 5.8. Differentialin vivothiol trapping revealed a disulfide bond between these two residues at pH 7.6, but not at pH 5.8. When Cys208 and Cys272 were replaced by aspartate and lysine, respectively, virtually wild-type behavior was restored indicating that the disulfide bond could be mimicked by a salt bridge.

Conclusion

A disulfide bond was found in the periplasmic domain of CadC that supports an inactive state of CadC at pH 7.6. At pH 5.8 disulfide bond formation is prevented which transforms CadC into a semi-active state. These results provide new insights into the function of a pH sensor.
OryzaPG-DB: Rice Proteome Database based on Shotgun Proteogenomics
Authors: Helmy Mohamed , Tomita Masaru , Ishihama Yasushi
Published: April 2011

Background

Proteogenomics aims to utilize experimental proteome information for refinement of genome annotation. Since mass spectrometry-based shotgun proteomics approaches provide large-scale peptide sequencing data with high throughput, a data repository for shotgun proteogenomics would represent a valuable source of gene expression evidence at the translational level for genome re-annotation.

Description

Here, we present OryzaPG-DB, a rice proteome database based on shotgun proteogenomics, which incorporates the genomic features of experimental shotgun proteomics data. This version of the database was created from the results of 27 nanoLC-MS/MS runs on a hybrid ion trap-orbitrap mass spectrometer, which offers high accuracy for analyzing tryptic digests from undifferentiated cultured rice cells. Peptides were identified by searching the product ion spectra against the protein, cDNA, transcript and genome databases from Michigan State University, and were mapped to the rice genome. Approximately 3200 genes were covered by these peptides and 40 of them contained novel genomic features. Users can search, download or navigate the database per chromosome, gene, protein, cDNA or transcript and download the updated annotations in standard GFF3 format, with visualization in PNG format. In addition, the database scheme of OryzaPG was designed to be generic and can be reused to host similar proteogenomic information for other species. OryzaPG is the first proteogenomics-based database of the rice proteome, providing peptide-based expression profiles, together with the corresponding genomic origin, including the annotation of novelty for each peptide.

Conclusions

The OryzaPG database was constructed and is freely available at http://oryzapg.iab.keio.ac.jp/.
Does age matter? - A MRI study on peritumoral edema in newly diagnosed primary glioblastoma
Authors: Seidel Clemens , Dörner Nils , Osswald Matthias , Wick Antje , Platten Michael , Bendszus Martin , Wick Wolfgang
Published: April 2011

Background

Peritumoral edema is a characteristic feature of malignant glioma related to the extent of neovascularisation and to vascular endothelial growth factor (VEGF) expression.

The extent of peritumoral edema and VEGF expression may be prognostic for patients with glioblastoma. As older age is a negative prognostic marker and as VEGF expression is reported to be increased in primary glioblastoma of older patients, age-related differences in the extent of peritumoral edema have been assessed.

Methods

In a retrospective, single-center study, preoperative magnetic resonance imaging (MRI) scans of steroid-naïve patients (n = 122) of all age groups were analysed. Patients with clinically suspected, radiologically likely or known evidence of secondary glioblastoma were not included.

Extent of brain edema was determined in a metric quantitative fashion and in a categorical fashion in relation to tumor size. Analysis was done group-wise related to age. Additionally, tumor size, degree of necrosis, superficial or deep location of tumor and anatomic localization in the brain were recorded.

Results

The extent of peritumoral edema in patients >65 years (ys) was not different from the edema extent in patients ≤ 65 ys (p = 0.261). The same was true if age groups ≤ 55 ys and ≥ 70 ys were compared (p = 0.308). However, extent of necrosis (p = 0.023), deep tumor localization (p = 0.02) and frontal localisation (p = 0.016) of the tumor were associated with the extent of edema. Tumor size was not linearly correlated to edema extent (Pearson F = 0.094, p = 0.303) but correlated to degree of necrosis (F = 0.355, p < 0.001, Spearman-Rho) and depth of tumor (p < 0.001). In a multifactorial analysis of maximum edema with the uncorrelated factors age, regional location of tumor and degree of necrosis, only the extent of necrosis (p = 0.022) had a significant effect.

Conclusion

Age at diagnosis does not determine degree of peritumoral edema, and tumor localization in the white matter is associated with greater extent of edema. The area of necrosis is reflective of volume of edema. In summary, the radiographic appearance of a glioblastoma at diagnosis does not reflect biology in the elderly patient.
Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: in vitro and in vivostudies
Authors: Cheung Stanley CK , Liu Li-zhong , Lan Lin-lin , Liu Qiao-quan , Sun Samuel SM , Chan Juliana CN , Tong Peter CY
Published: April 2011

Background

Human insulin-like growth factor-I (hIGF-I) is a growth factor which is highly resemble to insulin. It is essential for cell proliferation and has been proposed for treatment of various endocrine-associated diseases including growth hormone insensitivity syndrome and diabetes mellitus. In the present study, an efficient plant expression system was developed to produce biologically active recombinant hIGF-I (rhIGF-I) in transgenic rice grains.

Results

The plant-codon-optimized hIGF-I was introduced into rice viaAgrobacterium-mediated transformation. To enhance the stability and yield of rhIGF-I, the endoplasmic reticulum-retention signal and glutelin signal peptide were used to deliver rhIGF-I to endoplasmic reticulum for stable accumulation. We found that only glutelin signal peptide could lead to successful expression of hIGF-I and one gram of hIGF-I rice grain possessed the maximum activity level equivalent to 3.2 micro molar of commercial rhIGF-I.In vitrofunctional analysis showed that the rice-derived rhIGF-I was effective in inducing membrane ruffling and glucose uptake on rat skeletal muscle cells. Oral meal test with rice-containing rhIGF-I acutely reduced blood glucose levels in streptozotocin-induced and Zucker diabetic rats, whereas it had no effect in normal rats.

Conclusion

Our findings provided an alternative expression system to produce large quantities of biologically active rhIGF-I. The provision of large quantity of recombinant proteins will promote further research on the therapeutic potential of rhIGF-I.
Characterization of n-Hexane sub-fraction of Bridelia micrantha (Berth) and its antimycobacterium activity
Authors: Green Ezekiel , Obi Lawrence C , Samie Amidou , Bessong Pascal O , Ndip Roland N
Published: April 2011

Background

Tuberculosis, caused by Mycobacterium tuberculosis (MTB), is the most notified disease in the world. Development of resistance to first line drugs by MTB is a public health concern. As a result, there is the search for new and novel sources of antimycobacterial drugs for example from medicinal plants. In this study we determined the in vitro antimycobacterial activity of n-Hexane sub-fraction from Bridelia micrantha (Berth) against MTB H37Ra and a clinical isolate resistant to all five first-line antituberculosis drugs.

Methods

The antimycobacterial activity of the n-Hexane sub-fraction of ethyl acetate fractions from acetone extracts of B. micrantha barks was evaluated using the resazurin microplate assay against two MTB isolates. Bioassay-guided fractionation of the ethyl acetate fraction was performed using 100% n-Hexane and Chloroform/Methanol (99:1) as solvents in order of increasing polarity by column chromatography and Resazurin microtiter plate assay for susceptibility tests.

Results

The n-Hexane fraction showed 20% inhibition of MTB H37Ra and almost 35% inhibition of an MTB isolate resistant to all first-line drugs at 10 μg/mL. GC/MS analysis of the fraction resulted in the identification of twenty-four constituents representing 60.5% of the fraction. Some of the 24 compounds detected included Benzene, 1.3-bis (3-phenoxyphenoxy (13.51%), 2-pinen-4-one (10.03%), N(b)-benzyl-14-(carboxymethyl) (6.35%) and the least detected compound was linalool (0.2%).

Conclusions

The results show that the n- Hexane fraction of B. micrantha has antimycobacterial activity.
Isocaloric intake of a high-fat diet modifies adiposity and lipid handling in a sex dependent manner in rats
Authors: Estrany Maria E , Proenza Ana M , Lladó Isabel , Gianotti Magdalena
Published: April 2011

Background

High-fat (HF) diet feeding usually leads to hyperphagia and body weight gain, but macronutrient proportions in the diet can modulate energy intake and fat deposition. The mechanisms of fat accumulation and mobilization may differ significantly between depots, and gender can also influence these differences.

Aim

To investigate, in rats of both sexes, the effect of an isocaloric intake of a diet with an unbalanced proportion of macronutrients on fatty acid composition of visceral and subcutaneous adipose tissues and how this is influenced by both dietary fatty acids and levels of proteins involved in tissue lipid handling.

Methods

Eight-week-old Wistar rats of both sexes were fed a control diet (3% w/w fat) or high-fat diet (30% w/w fat) for 14 weeks. Fatty acid composition was analyzed by gas-chromatography and levels of LPL, HSL, α2-AR, β3-AR, PKA and CPT1 were determined by Western blot.

Results

The HF diet did not induce hyperphagia or body weight gain, but promoted an increase of adiposity index only in male rats. HF diet produced an increase of the proportion of MUFA and a decrease in that of PUFA in both adipose depots and in both sexes. The levels of proteins involved in the adrenergic control of the lipolytic pathway increased in the gonadal fat of HF females, whereas LPL levels increased in the inguinal fat of HF males and decreased in that of females.

Conclusion

Sexual dimorphism in adiposity index reflects a differential sex response to dietary fatty acid content and could be related to the levels of the proteins involved in tissue lipid management.
Oleic acid induces smooth muscle foam cell formation and enhances atherosclerotic lesion development via CD36
Authors: Ma Shuangtao , Yang Dachun , Li De , Tang Bing , Yang Yongjian
Published: April 2011

Background

Elevated plasma free fatty acid (FFA) levels have been linked to the development of atherosclerosis. However, how FFA causes atherosclerosis has not been determined. Because fatty acid translocase (FAT/CD36) is responsible for the uptake of FFA, we hypothesized that the atherogenic effects of FFA may be mediated via CD36.

Results

We tested this hypothesis using cultured rat aortic smooth muscle cells (SMCs) treated with oleic acid (OA). We found that OA induces lipid accumulation in SMCs in a dose dependent manner. Rat aortic SMCs treated for 48 hours with OA (250 μmol/L) became foam cells based on morphological (Oil Red O staining) and biochemical (5 times increase in cellular triglyceride) criteria. Moreover, specific inhibition of CD36 by sulfo-N-succinimidyl oleate significantly attenuated OA induced lipid accumulation and foam cell formation. To confirm these results in vivo, we used ApoE-deficient mice fed with normal chow (NC), OA diet, NC plus lipolysis inhibitor acipimox or OA plus acipimox. OA-fed mice showed increased plasma FFA levels and enhanced atherosclerotic lesions in the aortic sinus compared to the NC group (both p < 0.01). This effect was partially reversed by acipimox (lesion area: OA: 3.09 ± 0.10 ×105 μm2 vs. OA plus acipimox: 2.60 ± 0.10 ×105 μm2, p < 0.05; FFA: OA: 0.91 ± 0.03 mmol/L vs. OA plus acipimox: 0.78 ± 0.03 mmol/L, p < 0.05).

Conclusions

These findings suggest that OA induces smooth muscle foam cell formation and enhances atherosclerotic lesions in part though CD36. Furthermore, these findings provide a novel model for the investigation of atherosclerosis.
A protocol to assess cell cycle and apoptosis in human and mouse pluripotent cells
Authors: Edel Michael J , Menchon Cristina , Vaquero Jose MiguelAndres , Izpisua Belmonte JuanCarlos
Published: April 2011

Embryonic stem cells (ESC) and induced pluripotent stem cells (iPSCs) present a great opportunity to treat and model human disease as a cell replacement therapy. There is a growing pressure to understand better the signal transduction pathways regulating pluripotency and self-renewal of these special cells in order to deliver a safe and reliable cell based therapy in the near future. Many signal transduction pathways converge on two major cell functions associated with self-renewal and pluripotency: control of the cell cycle and apoptosis, although a standard method is lacking across the field. Here we present a detailed protocol to assess the cell cycle and apoptosis of ESC and iPSCs as a single reference point offering an easy to use standard approach across the field.
Rational design of HIV vaccines and microbicides: report of the EUROPRISE network annual conference 2010
Authors: Brinckmann Sarah , da Costa Kelly , van Gils Marit J , Hallengärd David , Klein Katja , Madeira Luisa , Mainetti Lara , Palma Paolo , Raue Katharina , Reinhart David , Reudelsterz Marc , Ruffin Nicolas , Seifried Janna , Schäfer Katrein , Sheik-Khalil Enas , Sköld Annette , Uchtenhagen Hannes , Vabret Nicolas , Ziglio Serena , Scarlatti Gabriella , Shattock Robin , Wahren Britta , Gotch Frances
Published: April 2011

Novel, exciting intervention strategies to prevent infection with HIV have been tested in the past year, and the field is rapidly evolving. EUROPRISE is a network of excellence sponsored by the European Commission and concerned with a wide range of activities including integrated developmental research on HIV vaccines and microbicides from discovery to early clinical trials. A central and timely theme of the network is the development of the unique concept of co-usage of vaccines and microbicides. This review, prepared by the PhD students of the network captures much of the research ongoing between the partners. The network is in its 5th year and involves over 50 institutions from 13 European countries together with 3 industrial partners; GSK, Novartis and Sanofi-Pasteur. EUROPRISE is involved in 31 separate world-wide trials of Vaccines and Microbicides including 6 in African countries (Tanzania, Mozambique, South Africa, Kenya, Malawi, Rwanda), and is directly supporting clinical trials including MABGEL, a gp140-hsp70 conjugate trial and HIVIS, vaccine trials in Europe and Africa.
Genetic diversity and multiple introductions of porcine reproductive and respiratory syndrome viruses in Thailand
Authors: Tun Hein M , Shi Mang , Wong Charles LY , Ayudhya Suparlark NN , Amonsin Alongkorn , Thanawonguwech Roongroje , Leung Frederick CC
Published: April 2011

Porcine reproductive and respiratory syndrome virus (PRRSV) is prevalent in Thailand, causing a huge impact on the country's swine industry. Yet the diversity and origin of these Thai PRRSVs remained vague. In this context, we collected all the Thai PRRSV sequences described earlier and incorporated them into the global diversity. The results indicated that PRRSVs in Thailand were originated from multiple introductions involving both Type 1 and Type 2 PRRSVs. Many of the introductions were followed by extensive geographic expansion, causing regional co-circulation of diverse PRRSV variants in three major pig-producing provinces. Based on these results, we suggest (1) to avoid blind vaccination and to apply vaccines tailor-made for target diversity, (2) to monitor pig importation and transportation, and (3) to implement a better biosecurity to reduce horizontal transmissions as three potentially effective strategies of controlling PRRS in Thailand.
Gene Ontology Function prediction in Mollicutes using Protein-Protein Association Networks
Authors: Gómez Antonio , Cedano Juan , Amela Isaac , Planas Antoni , Piñol Jaume , Querol Enrique
Published: April 2011

Background

Many complex systems can be represented and analysed as networks. The recent availability of large-scale datasets, has made it possible to elucidate some of the organisational principles and rules that govern their function, robustness and evolution. However, one of the main limitations in using protein-protein interactions for function prediction is the availability of interaction data, especially for Mollicutes. If we could harness predicted interactions, such as those from a Protein-Protein Association Networks (PPAN), combining several protein-protein network function-inference methods with semantic similarity calculations, the use of protein-protein interactions for functional inference in this species would become more potentially useful.

Results

In this work we show that using PPAN data combined with other approximations, such as functional module detection, orthology exploitation methods and Gene Ontology (GO)-based information measures helps to predict protein function in Mycoplasma genitalium.

Conclusions

To our knowledge, the proposed method is the first that combines functional module detection among species, exploiting an orthology procedure and using information theory-based GO semantic similarity in PPAN of the Mycoplasma species. The results of an evaluation show a higher recall than previously reported methods that focused on only one organism network.
Identification of a novel intronic enhancer responsible for the transcriptional regulation of musashi1 in neural stem/progenitor cells
Authors: Kawase Satoshi , Imai Takao , Miyauchi-Hara Chikako , Yaguchi Kunio , Nishimoto Yoshinori , Fukami Shin-ichi , Matsuzaki Yumi , Miyawaki Atsushi , Itohara Shigeyoshi , Okano Hideyuki
Published: April 2011

Background

The specific genetic regulation of neural primordial cell determination is of great interest in stem cell biology. The Musashi1 (Msi1) protein, which belongs to an evolutionarily conserved family of RNA-binding proteins, is a marker for neural stem/progenitor cells (NS/PCs) in the embryonic and post-natal central nervous system (CNS). Msi1 regulates the translation of its downstream targets, including m-Numb and p21 mRNAs. In vitro experiments using knockout mice have shown that Msi1 and its isoform Musashi2 (Msi2) keep NS/PCs in an undifferentiated and proliferative state. Msi1 is expressed not only in NS/PCs, but also in other somatic stem cells and in tumours. Based on previous findings, Msi1 is likely to be a key regulator for maintaining the characteristics of self-renewing stem cells. However, the mechanisms regulating Msi1 expression are not yet clear.

Results

To identify the DNA region affecting Msi1 transcription, we inserted the fusion gene ffLuc, comprised of the fluorescent Venus protein and firefly Luciferase, at the translation initiation site of the mouse Msi1 gene locus contained in a 184-kb bacterial artificial chromosome (BAC). Fluorescence and Luciferase activity, reflecting the Msi1 transcriptional activity, were observed in a stable BAC-carrying embryonic stem cell line when it was induced toward neural lineage differentiation by retinoic acid treatment. When neuronal differentiation was induced in embryoid body (EB)-derived neurosphere cells, reporter signals were detected in Msi1-positive NSCs and GFAP-positive astrocytes, but not in MAP2-positive neurons. By introducing deletions into the BAC reporter gene and conducting further reporter experiments using a minimized enhancer region, we identified a region, "D5E2," that is responsible for Msi1 transcription in NS/PCs.

Conclusions

A regulatory element for Msi1 transcription in NS/PCs is located in the sixth intron of the Msi1 gene. The 595-bp D5E2 intronic enhancer can transactivate Msi1 gene expression with cell-type specificity markedly similar to the endogenous Msi1 expression patterns.
SynCAM1, a Synaptic Adhesion Molecule, Is Expressed in Astrocytes and Contributes to erbB4 Receptor-Mediated Control of Female Sexual Development
Authors: Sandau Ursula S. , Mungenast Alison E. , Alderman Zefora , Sardi S. Pablo , Fogel Adam I. , Taylor Bethany , Parent Anne-Simone , Biederer Thomas , Corfas Gabriel , Ojeda Sergio R.
Published: April 2011

Female sexual maturation requires erythroblastosis B (erbB)4 signaling in hypothalamic astrocytes; however, the mechanisms by which erbB4 contributes to this process are incompletely understood. Here we show that SynCAM1, a synaptic adhesion molecule with signaling capabilities, is not only expressed highly in neurons, but also in hypothalamic astrocytes and is functionally associated with erbB4 receptor activity. Whereas SynCAM1 expression is diminished in astrocytes with impaired erbB4 signaling, ligand-dependent activation of astroglial erbB4 receptors results in rapid association of erbB4 with SynCAM1 and activation of SynCAM1 gene transcription. To determine whether astrocytic SynCAM1-dependent intracellular signaling is required for normal female reproductive function, we generated transgenic mice that express in an astrocyte-specific manner a dominant-negative form of SynCAM1 lacking the intracellular domain. The mutant protein was correctly targeted to the cell membrane and was functionally viable as shown by its ability to block intracellular calcium/calmodulin-dependent serine protein kinase redistribution, a major SynCAM1-mediated event. Dominant-negative-SynCAM1 female mice had a delayed onset of puberty, disrupted estrous cyclicity, and reduced fecundity. These deficits were associated with a reduced capacity of neuregulin-dependent erbB4 receptor activation to elicit prostaglandin E2 release from astrocytes and GnRH release from the hypothalamus. We conclude that one of the mechanisms underlying erbB4 receptor-mediated facilitation of glial-neuronal interactions in the neuroendocrine brain involves SynCAM1-dependent signaling and that this interaction is required for normal female reproductive function.
The Call to Intimacy and the Shame Effect
Authors: Bewes Timothy
Published: April 2011

This article discusses Dicle Koğacıoğlu's 2004 essay “The Tradition Effect: Framing Honor Crimes in Turkey.” It considers Koğacıoğlu's formulation of the “tradition effect” in the light of several other “effects” put forward by social theorists and philosophers: the “individual effect” (Foucault), the “society effect” (Althusser), the “knowledge effect” (Althusser), and the “state effect” (Mitchell). Through a reading of Georg Lukács's essay “The Moment and Form” and J. M. Coetzee's novel Diary of a Bad Year, the article introduces two further effects to be placed alongside these: the “subject effect” and the “shame effect.” What links these different effects, the author argues, is that in every case the effect is closely tied to a process of naming or stepping forth— what is here called “instantiation.” A theoretical account of instantiation is therefore necessary if we are to understand the logic that underlies these different effects. To this end, we need to pay special attention to shame; for shame, uniquely, comes into existence as a profound discordance with its own instantiation.
Seductions of the “Honor Crime”
Authors: Abu-Lughod Lila
Published: April 2011

The “honor crime” poses perhaps more starkly than any other contemporary cultural-legal category the dilemmas of feminist scholarship and rights activism in a transnational world. Marked as a culturally specific form of violence and given a special and stigmatizing association with Muslims, especially after the 1990s, the honor crime does significant political work in the world today. Through an examination of popular literature, human rights reports, and anthropological and sociological studies, this article uncovers the forces that produce and maintain this category of spectacular cultural violence; the elements of popular fantasy that animate it; the forms of modern state and transnational power the category occludes; and the ahistorical and divisive civilizational thinking it encourages. Drawing both on ethnography from one Egyptian Bedouin community in which honor is a key moral value and on the critical analysis of diverse representations of the honor crime in Germany, Sweden, Palestine, Turkey, Jordan, and elsewhere, the author explores how the seductive power of the honor crime, mixing sexual titillation and moral horror, and its truly polymorphous interpretive capacity have enabled it to emerge as a robust category implicated in projects that include the policing and exclusions of immigrants; nation-states' disciplinary penetration of rural and urban subaltern communities; dominance by specific national, ethnic, or class groups; manipulation of liberal values in the service of assertions of Western superiority; and justifications of international intervention and transnational governance in the name of women's rights, including by feminists.
Undocumented Migrants and the Double Binds of Rights Claims
Authors: Parla Ayse
Published: April 2011

This article explores the potentials for and pitfalls of the virtually nonexistent terrain of rights for undocumented migrants in Turkey to engage the broader question of whether the language of rights can serve emancipatory ends for subordinated groups. As in other capitalist regimes, the question of the rights of undocumented migrants in Turkey presents a major paradox. On the one hand, the undocumented migrants' lack of right to residence, work, and social security intensifies their vulnerability in the flexible, predominantly informal labor market. On the other hand, rights claims risk naturalizing deeper structural inequalities as they simultaneously seek to ameliorate them. The predicament of Bulgarian Turkish migrants brings its own twist to the thorny question of rights for undocumented migrants. Historically the most privileged among migrants in Turkey because of their “Turkish origins,” the recent Turkish migrants from Bulgaria continue to deploy the language of ethnic privilege in pursuing their claims. While such particularistic claims may result in individual gains for some migrants, they tend to preclude collective forms of migrant organizing and foreclose the articulation of more radical political and economic demands. After demonstrating the double binds of the specific rights claims available to Bulgarian Turkish migrants in Turkey, the article concludes by pondering the possibilities for an alternative, incipient discourse of rights that takes labor rather than ethnicity as the basis of entitlement.
A Clock-Setting Institute for the Market Age: The Politics of Importing “Competition” To Turkey
Authors: Türem Z. Umut
Published: April 2011

What is the “work” of neoliberal legal technologies in the global south? What do the processes of their transplantation to and appropriation in the semi-peripheries of the global political economy tell us about the sociopolitical context that made these technologies possible? This article approaches these questions from an unusual angle, focusing on the passing of competition and antitrust laws and the establishment of a Competition Authority in Turkey alongside the story of a fictional institute called The Clock Setting Institute in Ahmet Hamdi Tanpınar's novel of the same name. Arguing that Tanpınar's story, and the modernization parody it constructs, offers significant insights that help bring to light otherwise invisible dimensions of neoliberal state reforms, the author discusses how neoliberalism and its technologies are translated into a language of modernization and appropriated as tools in the service of civilizing the nation, in Turkey and in the global south. This translation—and transformation—not only shows how an otherwise alien legal and economic technology takes root by being translated into the local lingua of statehood in Turkey but also highlights a remarkable continuity between the practices of the modernizing state and the neoliberal state. According to this article, the real work of neoliberal technologies, competition law, and economics consists of importing and mobilizing the “scientific” (economic) tools of representing the economic reality “out there.” Such representations, similar to what clocks do for the concept of time in Tanpinar's novel, end up in fact producing what is “out there.”
Cortical localization of APC2 plays a role in actin organization but not in Wnt signaling inDrosophila
Authors: Zhou Meng-Ning , Kunttas-Tatli Ezgi , Zimmerman Sandra , Zhouzheng Fangyuan , McCartney Brooke M.
Published: April 2011

The tumor suppressor Adenomatous polyposis coli (APC) has roles in both Wnt signaling and in actin and microtubule organization. Within the cell, APC proteins have been reported to localize in the cytoplasm, at the cell cortex and in the nucleus. How these localizations relate to the functions of the protein is an aspect of APC biology that is poorly understood. Using Drosophila S2 cells, we have dissected the structural and functional requirements for the cortical localization of Drosophila APC2. Here, we show that both the Armadillo repeats and a novel C-terminal domain are necessary for the cortical localization of APC2 in S2 cells and in the embryo, and that neither domain alone is sufficient for this localization. Furthermore, we show that the Armadillo repeats mediate self-association of APC2 molecules. To test the function of the cortical localization of APC2, we asked whether an APC2 protein deleted for the C-terminal localization domain could rescue APC mutant defects in Wnt signaling and actin organization in the Drosophila embryo. We show that although cortical localization is required for the APC2 function in organizing actin, cortical localization is dispensable for its role in regulating Wnt signaling.
Estrogen receptor mediates a distinct mitochondrial unfolded protein response
Authors: Papa Luena , Germain Doris
Published: April 2011

Unfolded protein responses (UPRs) of the endoplasmic reticulum and mitochondrial matrix have been described. Here, we show that the accumulation of proteins in the inter-membrane space (IMS) of mitochondria in the breast cancer cell line MCF-7 activates a distinct UPR. Upon IMS stress, overproduction of reactive oxygen species (ROS) and phosphorylation of AKT triggers estrogen receptor (ER) activity, which further upregulates the transcription of the mitochondrial regulator NRF1 and the IMS protease OMI (officially known as HTRA2). Moreover, we demonstrate that the IMS stress-induced UPR culminates in increased proteasome activity. Given our previous report on a proteasome- and OMI-dependent checkpoint that limits the import of IMS proteins, the findings presented in this study suggest that this newly discovered UPR acts as a cytoprotective response to overcome IMS stress.
Cortical actin dynamics driven by formins and myosin V
Authors: Yu Jerry H. , Crevenna Alvaro H. , Bettenbühl Mario , Freisinger Tina , Wedlich-Söldner Roland
Published: April 2011

Cell morphogenesis requires complex and rapid reorganization of the actin cytoskeleton. The budding yeast Saccharomyces cerevisiae is an invaluable model system for studying molecular mechanisms driving actin dynamics. Actin cables in yeast are formin-generated linear actin arrays that serve as tracks for directed intracellular transport by type V myosins. Cables are constantly reorganized throughout the cell cycle but the molecular basis for such dynamics remains poorly understood. By combining total internal reflection microscopy, quantitative image analyses and genetic manipulations we identify kinetically distinct subpopulations of cables that are differentially driven by formins and myosin. Bni1 drives elongation of randomly oriented actin cables in unpolarized cells, whereas both formins Bnr1 and Bni1 mediate slower polymerization of cables in polarized cells. Type V myosin Myo2 surprisingly acts as a motor for translational cable motility along the cell cortex. During polarization, cells change from fast to slow cable dynamics through spatio-temporal regulation of Bni1, Bnr1 and Myo2. In summary, we identify molecular mechanisms for the regulation of cable dynamics and suggest that fast actin reorganization is necessary for fidelity of cell polarization.
Endocytic membrane fusion and buckling-induced microtubule severing mediate cell abscission
Authors: Schiel John A. , Park Kristin , Morphew Mary K. , Reid Evan , Hoenger Andreas , Prekeris Rytis
Published: April 2011

Cytokinesis and abscission are complicated events that involve changes in membrane transport and cytoskeleton organization. We have used the combination of time-lapse microscopy and correlative high-resolution 3D tomography to analyze the regulation and spatio-temporal remodeling of endosomes and microtubules during abscission. We show that abscission is driven by the formation of a secondary ingression within the intracellular bridge connecting two daughter cells. The initiation and expansion of this secondary ingression requires recycling endosome fusion with the furrow plasma membrane and nested central spindle microtubule severing. These changes in endosome fusion and microtubule reorganization result in increased intracellular bridge plasma membrane dynamics and abscission. Finally, we show that central spindle microtubule reorganization is driven by localized microtubule buckling and breaking, rather than by spastin-dependent severing. Our results provide a new mechanism for mediation and regulation of the abscission step of cytokinesis.
Relative contribution of PECAM-1 adhesion and signaling to the maintenance of vascular integrity
Authors: Privratsky Jamie R. , Paddock Cathy M. , Florey Oliver , Newman Debra K. , Muller William A. , Newman Peter J.
Published: April 2011

PECAM-1 (CD31) is a cellular adhesion and signaling receptor that is highly expressed at endothelial cell–cell junctions in confluent vascular beds. Previous studies have implicated PECAM-1 in the maintenance of vascular barrier integrity; however, the mechanisms behind PECAM-1-mediated barrier protection are still poorly understood. The goal of the present study, therefore, was to examine the pertinent biological properties of PECAM-1 (i.e. adhesion and/or signaling) that allow it to support barrier integrity. We found that, compared with PECAM-1-deficient endothelial cells, PECAM-1-expressing endothelial cell monolayers exhibit increased steady-state barrier function, as well as more rapid restoration of barrier integrity following thrombin-induced perturbation of the endothelial cell monolayer. The majority of PECAM-1-mediated barrier protection was found to be due to the ability of PECAM-1 to interact homophilically and become localized to cell–cell junctions, because a homophilic binding-crippled mutant form of PECAM-1 was unable to support efficient barrier function when re-expressed in cells. By contrast, cells expressing PECAM-1 variants lacking residues known to be involved in PECAM-1-mediated signal transduction exhibited normal to near-normal barrier integrity. Taken together, these studies suggest that PECAM-1–PECAM-1 homophilic interactions are more important than its signaling function for maintaining the integrity of endothelial cell junctions.
Phenotypes of pseudohypoaldosteronism type II caused by the WNK4 D561A missense mutation are dependent on the WNK-OSR1/SPAK kinase cascade
Authors: Chiga Motoko , Rafiqi Fatema H. , Alessi Dario R. , Sohara Eisei , Ohta Akihito , Rai Tatemitsu , Sasaki Sei , Uchida Shinichi
Published: April 2011

We recently reported increased phosphorylation of the NaCl cotransporter (NCC) in Wnk4D561A/+ knock-in mice, an ideal model of the human hereditary hypertensive disease pseudohypoaldosteronism type II (PHAII). Although previous in vitro studies had suggested the existence of a phosphorylation cascade involving the WNK, OSR1 and SPAK kinases, whether the WNK-OSR1/SPAK cascade is in fact fully responsible for NCC phosphorylation in vivo and whether the activation of this cascade is the sole mediator of PHAII remained to be determined. To clarify these issues, we mated the Wnk4D561A/+ knock-in mice with Spak and Osr1 knock-in mice in which the T-loop threonine residues in SPAK and OSR1 (243 and 185, respectively) were mutated to alanine to prevent activation by WNK kinases. We found that NCC phosphorylation was almost completely abolished in Wnk4D561A/+SpakT243A/T243AOsr1T185A/+ triple knock-in mice, clearly demonstrating that NCC phosphorylation in vivo is dependent on the WNK-OSR1/SPAK cascade. In addition, the high blood pressure, hyperkalemia and metabolic acidosis observed in Wnk4D561A/+ mice were corrected in the triple knock-in mice. These results clearly establish that PHAII caused by the WNK4 D561A mutation is dependent on the activation of the WNK-OSR1/SPAK-NCC cascade and that the contribution of other mechanisms to PHAII (independent of the WNK-OSR1/SPAK cascade) could be minimal.
Staying the course: chemical signal spatial properties and concentration mediate cross-stream motion in turbulent plumes
Authors: Page Jennifer L. , Dickman Brian D. , Webster Donald R. , Weissburg Marc J.
Published: April 2011

This study examined the role of broadly distributed sensor populations in chemosensory searching, especially cross-stream heading adjustment. We used three-dimensional laser-induced fluorescence to collect chemical concentration data simultaneously with behavior observations of actively tracking blue crabs (Callinectes sapidus). Our analysis indicates that the spatial distribution of the odorant concentration field is necessary and sufficient to mediate correct cross-stream motion, although concentration provides information that supplements that obtained from the spatial distribution. Crab movement is continually adjusted to maintain an upstream heading, with corrections toward the source modulated only in the presence of chemical cues. Crabs detect and respond to shifts in the position of the center-of-mass (COM) of the odorant concentration distribution as small as 5% of the leg span, which corresponds to ∼0.8–0.9 cm. The reaction time after a 5% threshold shift in the position of the COM is in the range of 2–4 s. Data also indicate that these steering responses are dependent on stimulus history or other characteristics of the plume, with crabs taking longer to respond in conditions with large-scale spatial meanders. Although cross-stream motion is determined by chemical signal inputs to receptors on the walking legs, crabs do make rotational movements in response to chemical signals impinging on the antennules. These rotational movements do not affect the direction of travel, but rather, determine the crab's body angle with respect to the flow. Interestingly, these body angles seem to represent a compromise between reducing drag and obtaining better chemical signal information, and this trade-off is resolved differently under different plume conditions.
Insulin-like peptide genes in honey bee fat body respond differently to manipulation of social behavioral physiology
Authors: Nilsen Kari-Anne , Ihle Kate E. , Frederick Katy , Fondrk M. Kim , Smedal Bente , Hartfelder Klaus , Amdam Gro V.
Published: April 2011

Nutrient sensitive insulin-like peptides (ILPs) have profound effects on invertebrate metabolism, nutrient storage, fertility and aging. Many insects transcribe ILPs in specialized neurosecretory cells at changing levels correlated with life history. However, the major site of insect metabolism and nutrient storage is not the brain, but rather the fat body, where functions of ILP expression are rarely studied and poorly understood. Fat body is analogous to mammalian liver and adipose tissue, with nutrient stores that often correlate with behavior. We used the honey bee (Apis mellifera), an insect with complex behavior, to test whether ILP genes in fat body respond to experimentally induced changes of behavioral physiology. Honey bee fat body influences endocrine state and behavior by secreting the yolk protein precursor vitellogenin (Vg), which suppresses lipophilic juvenile hormone and social foraging behavior. In a two-factorial experiment, we used RNA interference (RNAi)-mediated vg gene knockdown and amino acid nutrient enrichment of hemolymph (blood) to perturb this regulatory module. We document factor-specific changes in fat body ilp1 and ilp2 mRNA, the bee's ILP-encoding genes, and confirm that our protocol affects social behavior. We show that ilp1 and ilp2 are regulated independently and differently and diverge in their specific expression-localization between fat body oenocyte and trophocyte cells. Insect ilp functions may be better understood by broadening research to account for expression in fat body and not only brain.