bluuebunny/crossref_metadata_2025 huggingface dataset:
We are Sweden Democrats because we care for others: Exploring racisms in the Swedish extreme right
Authors: Mulinari Diana , Neergaard Anders
Published: November 2013

During the last decades there has been an upsurge in research on xenophobic populist parties, mirroring their political successes. In the Swedish context, characterised by neoliberal restructuring, issues of ‘race’, citizenship and belonging have been important elements of the public debate. These issues have unfolded in parallel with the presence of a neo-Nazi social movement and the emergence of two new parliamentary parties in which cultural racism has been central. Research has especially focused on the xenophobic content and how to relate these parties to the wider research on party politics in western liberal democracies. While there have been some studies focusing on gendered differences in voting and activism highlighting the peripheral role of women, there are still very few studies analysing the worldview of women active in these parties, and the role of gender as metaphor, identity and policy within these parties. Inspired by feminist, postcolonial and Marxist research, the authors of this article are interested in analysing the worldview of women activists. The material is composed of 20 in-depth interviews with female Sweden Democrat politicians complemented by party texts and participant observation. The aim of the article is to explore how women within a Swedish version of these parties, the Sweden Democrats, name and reflect upon their experiences, especially focusing on how a care rhetoric is used in their narratives. These women have chosen to represent a racist party (although they do not see themselves or the party as racist). What inspires them? What visions of gender evolve from their worldview?
Private Speech During Problem-Solving Activities in Bilingual Speakers
Authors: Jiménez Jiménez Antonio F.
Published: November 2013

Based on the tenets of Vygotsky’s sociocultural theory, this research study investigated the private speech produced by 30 adult English/Spanish bilinguals while engaged in a problem-solving activity, with the objective of better understanding the regulatory role that each language plays in the bilingual mind. In order to obtain a spontaneous production of private speech, participants were unknowingly audio-recorded while working in a private room on 15 challenging questions in Spanish, which included problems of logic, mathematics, visual-spatial problems, and kinship questions. The 30 early bilinguals who participated were divided into three groups: The Spanish-dominant group, the English-dominant group, and the balanced group, who consisted of bilinguals who reported to be equally comfortable in both languages. Results showed that bilinguals’ dominant language played an important regulatory role in their verbalized thinking while the other language provided a complementary set of cognitive resources and strategies that were employed when needed.
Possibilities for and limits to enforcing tax compliance measures on ‘irregular’ workers
Authors: Rothengatter Maarten
Published: November 2013

This article is a contribution to ongoing studies of tax compliance by Australian taxi-cab operators and their drivers. The limits of the dominant academic literature and the industry-specific legislation on tax conformity will be assessed. The article’s core premise is that social and economic activities (legal and illicit) of cab drivers are embedded within unique networks of social relations. Cab drivers are subjected to a multitude of structural arrangements and informal social control mechanisms, which influence their attitudes and actions with regard to tax compliance. Regulatory initiatives towards diminishing non-compliance in the Australian taxi-cab industry continue to ignore the concept of mixed embeddedness and the interrelatedness between compliance rules, enforcement practices and broader legislative framework. It will be argued that changes to the employment status of Australian taxi drivers can produce a more expedient way for curtailing the deeply entrenched tax non-compliant modus operandi within this particular sector of Australia’s transport-services industry.
Family matters: Women who ‘marry’ women in Iceland
Authors: Einarsdóttir Anna
Published: November 2013

This article is based on study among women who ‘married’ other women in Iceland. It reveals complexity and controversial issues of visibility and acceptance, and illustrates the differing reception that same-sex partnership recognition receives in public, within families and within the non-heterosexual community in general. While same-sex partnership recognition has the potential to shape public opinion in positive ways, marriage neither guarantees acceptance from family nor does it automatically lead to visibility. These findings are interesting in light of the growing body of literature on the fading importance of tradition, growing individualization and the decline of the nuclear family, as they act to complicate such claims, showing that it is precisely through traditional family rituals that acceptance of same-sex relationships is communicated in small close-knit communities.
A new hybrid bonding technique: Adhesive-soft soldered joints
Authors: Kavak N , Altan E
Published: November 2013

Joining of components is usually accomplished by mechanical fastening, welding, or adhesive bonding. Apart from the classical methods, various hybrid methods applied with adhesives are widely used in industry to bond mechanical parts. This study describes a new hybrid bonding method as an alternative to currently used hybrid methods: adhesive-soft soldered joints. In this new hybrid technique, joints are made by adding various (5 wt%, 15 wt%, 25 wt%, and 50 wt%) amounts of soft soldering alloy powder into the adhesive at two different temperatures (180℃ and 200℃). The strength of the joints is measured by tensile shear tests. The mechanical strength of adhesive joints carried out by adding soft soldering powder melted at 200℃ is higher than that of joints with only adhesives and unmelted soft soldering powders. The developed hybrid method is applied to attach the insert to cutting tools used in the machining industry and the feasibility of the method is investigated with experiments.
Queer Sweet Home
Authors: Wight Jules
Published: November 2013

This project draws together queer and phenomenological perspectives, stressing a critical orientation of digital interfaces and digital space. I investigate the surfaces of these digital geographies as well as the otherwise underlying orientations and disorientations of/in digital social place. More specifically, I use the It Gets Better Project as a case study to describe places of everyday practice in digital space as place and as home—turning, or queering, the idea of home away from normative conceptualizations of home as being physically situated and toward a possibility for home in the digital and mediated. While digital place can serve as digital home for transgender youth, there are also aspects of digital home in the popular online campaign that have the potential to do injury and create unrest. Those who find home in the digital also engage or contend with the current digital landscapes of surveillance, continued media conglomerates, digital divides, neoliberal ideologies, and circularly destructive political economies.
Towards a diagnostic approach to media in fragile states: Examples from the Somali territories
Authors: Stremlau Nicole
Published: November 2013

Media interventions by international organizations and NGOs in conflict and post-conflict situations seek to develop and shape a media system to contribute to specific political and social ends. The analyses and assessments that inform these interventions are often based on an overview of the formal media and governance structures, such as mass media and state institutions, and overlook informal structures that may be instrumental for political and development goals. This article proposes a framework that can incorporate both the formal and informal modes of communication and participation that characterize a society. This framework encourages a ‘diagnostic’ approach centred around three areas: power, flows, and participation, and enables researchers to take into consideration features that are often overlooked such as customary law; a range of public authorities from politicians to Imams and local elders; information flows that may vary from poetry to mobile phones; and the culture of communication. Examples from the Somali territories, which are characterized by a weak central government, are employed to highlight how informal structures and actors intervene in shaping information flows and the importance of accounting for them.
The new breed of Chinese war correspondents: Their motivations and roles, and the impact of digital technology
Authors: Zhang Shixin Ivy
Published: November 2013

The reporting of international news in China has changed significantly in recent years. Since the late 1990s, driven by the demands of the domestic market, the growing financial strengths of national and metropolitan news organizations, the availability of digital technology, and the state’s strategy of enhancing soft power and making China’s voice heard in the global arena, more and more Chinese correspondents travel to war and conflict zones abroad to report and file news coverage back home – a rare occurrence in the past. This study examines a new breed of Chinese war correspondents arising from this very new journalistic environment – how they negotiate their changing and challenging roles by questioning their identities, motivations and perceptions, and how they reflect on their roles, and the use and impact of digital technologies such as micro-blogging. This article uses semi-structured in-depth interviews with 16 Chinese correspondents who have been posted abroad to cover war zones. The author finds that this new breed is neither traditionally Chinese in their approach nor western in their perceptions but uniquely pragmatic in negotiating a complex mix of identities, motivations, corporate influences and state interests.
CASALUD: an innovative health-care system to control and prevent non-communicable diseases in Mexico
Authors: Tapia-Conyer Roberto , Gallardo-Rincón Héctor , Saucedo-Martinez Rodrigo
Published: November 2013

Mexico and other Latin American countries are currently facing a dramatic increase in the number of adults suffering from non-communicable diseases (NCDs) such as diabetes, cardiovascular disease (CVD) and chronic kidney disease (CKD), which require prolonged, continuous care. This epidemiological shift has created new challenges for health-care systems. Both the World Health Organization (WHO) and the United Nations (UN) have recognised the growing human and economic costs of NCDs and outlined an action plan, recognising that NCDs are preventable, often with common preventable risk factors linked to risky health behaviours. In line with international best practices, Mexico has applied a number of approaches to tackle these diseases. However, challenges remain for the Mexican health-care system, and in planning a strategy for combating and preventing NCDs, it must consider how best to integrate these strategies with existing health-care infrastructure. Shifting the paradigm of care in Mexico from a curative, passive approach to a preventive, proactive model will require an innovative and replicable system that guarantees availability of medicines and services, strengthens human capital through ongoing professional education, expands early and continuous access to care through proactive prevention strategies and incorporates technological innovations in order to do so. Here, we describe CASALUD: an innovative model in health-care that leverages international best practices and uses innovative technology to deliver NCD care, control and prevention. In addition, we describe the lessons learned from the initial implementation of the model for its effective use in Mexico, as well as the plans for wider implementation throughout the country, in partnership with the Mexican Ministry of Health.
The Art and Science of Political Advocacy
Authors: Kosiorowski Donna
Published: November 2013

School nurses throughout the nation, individually and collectively, work to bring about change for the school nursing profession and to safeguard the health of children and the public. School nurses practice amidst education reform, health care reform, changes in society, and medical and technological advancements. School nurses must be active in decisions that affect their daily practice by involvement in the local, state, and federal political process. School nurses must craft the art and develop the science of political advocacy.
Enhanced in vitro osteoblast differentiation on TiO2 scaffold coated with alginate hydrogel containing simvastatin
Authors: Pullisaar Helen , Tiainen Hanna , Landin Maria A , Lyngstadaas Ståle P , Haugen Håvard J , Reseland Janne E , Østrup Esben
Published: November 2013

The aim of this study was to develop a three-dimensional porous bone graft material as vehicle for simvastatin delivery and to investigate its effect on primary human osteoblasts from three donors. Highly porous titanium dioxide (TiO2) scaffolds were submerged into simvastatin containing alginate solution. Microstructure of scaffolds, visualized by scanning electron microscopy and micro-computed tomography, revealed an evenly distributed alginate layer covering the surface of TiO2 scaffold struts. Progressive and sustained simvastatin release was observed for up to 19 days. No cytotoxic effects on osteoblasts were observed by scaffolds with simvastatin when compared to scaffolds without simvastatin. Expression of osteoblast markers (collagen type I alpha 1, alkaline phosphatase, bone morphogenetic protein 2, osteoprotegerin, vascular endothelial growth factor A and osteocalcin) was quantified using real-time reverse transcriptase–polymerase chain reaction. Secretion of osteoprotegerin, vascular endothelial growth factor A and osteocalcin was analysed by multiplex immunoassay (Luminex). The relative expression and secretion of osteocalcin was significantly increased by cells cultured on scaffolds with 10 µM simvastatin when compared to scaffolds without simvastatin after 21 days. In addition, secretion of vascular endothelial growth factor A was significantly enhanced from cells cultured on scaffolds with both 10 nM and 10 µM simvastatin when compared to scaffolds without simvastatin at day 21. In conclusion, the results indicate that simvastatin-coated TiO2 scaffolds can support a sustained release of simvastatin and induce osteoblast differentiation. The combination of the physical properties of TiO2 scaffolds with the osteogenic effect of simvastatin may represent a new strategy for bone regeneration in defects where immediate load is wanted or unavailable.
Effect of aging temperature on microstructure and mechanical properties of different rolling orientations in novel Al–Li alloy
Authors: Du Z. L. , Zeng W. D. , Yang W. H. , Zhang C. , Shi C. L. , Wang H. J. , Zhou Z. P.
Published: November 2013

Microstructure and properties of different rolling orientation with aging temperature varying in a newly developed Al–Li alloy was investigated by transmission electron microscopy (TEM) analysis. Sheets of experimental Al–Li alloy were solution treated at 510°C for 2 h. Predeformation of ∼3 was stretched in the 0 and 90° angle with respect to the original rolling orientation before aging treatment. All specimens were aged for 35 h at 138, 143, 148, 153, 158 and 163°C respectively. Tensile specimens were stretched along the previous orientation of predeformation. The results showed that the main strengthening phases in the alloy were δ′ (Al3Li), θ′ (Al2Cu)/ θ″ (Guinier–Preston II zone), δ′/ β′ (Al3Zr) and T1 (Al2CuLi) phase. Among the phases above, the strengthening effect of T1 phase surpassed the others. Moreover, very little of cubic σ (Al5Cu6Mg2) phase was observed in the alloy. The microstructure evolution was similar via comparing sheets in different stretched directions. At initial stage of aging, a large amount of fine T1, δ′, δ′/ β′ and θ′/ θ″ phases uniformly distributed in Al matrix with the aging temperature increasing. Subsequently, the quantity and size of T1 phase increased gradually. In the middle and later period, T1 phase was the main phase that grew at the cost of other phases. The peak aged temperature was 158°C with yield strength of 540 MPa when stretched at 0° angle to the original rolling orientation and 501 MPa when at 90° angle to the rolling direction. Meanwhile, the elongations were 9·5 and 10·9 respectively, which indicated that the anisotropy of the alloy was not obvious.
Recombinant production and characterization of full-length and truncated β-1,3-glucanase PglA from Paenibacillussp. S09
Authors: Cheng Rui , Chen Jinping , Yu Xiaohong , Wang Yang , Wang Shiming , Zhang Jianfa
Published: November 2013

Background

β-1,3-Glucanases catalyze the hydrolysis of glucan polymers containing β-1,3-linkages. These enzymes are of great biotechnological, agricultural and industrial interest. The applications of β-1,3-glucanases is well established in fungal disease biocontrol, yeast extract production and wine extract clarification. Thus, the identification and characterization of novel β-1,3-glucanases with high catalytic efficiency and stability is of particular interest.

Results

A β-1,3-glucanase gene designated PglA was cloned from a newly isolated strain Paenibacillus sp. S09. The gene PglA contained a 2631-bp open reading frame encoding a polypeptide of 876 amino acids which shows 76% identity with the β-1,3-glucanase (BglH) from Bacillus circulans IAM1165. The encoded protein PglA is composed of a signal peptide, an N-terminal leader region, a glycoside hydrolase family 16 (GH16) catalytic domain and a C-terminal immunoglobulin like (Ig-like) domain. The Escherichia coli expression system of PglA and five truncated derivatives containing one or two modules was constructed to investigate the role of catalytic and non-catalytic modules. The pH for optimal activity of the enzymes was slightly affected (pH 5.5-6.5) by the presence of different modules. However, the temperature for optimal activity was strongly influenced by the C-terminal domain and ranged from 50 to 60°C. Deletion of C-terminal domain resulted in obviously enhancing enzymatic thermostability. Specific activity assay indicated that PglA specifically hydrolyzes β-1,3-glucan. Insoluble β-1,3-glucan binding and hydrolysis were boosted by the presence of N-and C-terminal domains. Kinetic analysis showed that the presence of N-and C-terminus enhances the substrate affinity and catalytic efficiency of the catalytic domain toward laminarin. Carbohydrate-binding assay directly confirmed the binding capabilities of the N-and C-terminal domains.

Conclusions

This study provides new insight into the impacts of non-catalytic modules on enzymatic properties of β-1,3-glucanase. Activity comparison of full-length PglA and truncated forms revealed the negative effect of C-terminal region on thermal stability of the enzyme. Both the N-and C-terminal domains exerted strong binding activity toward insoluble β-1,3-glucan, and could be classified into CBM families.
Comparison of the antibacterial activity of essential oils and extracts of medicinal and culinary herbs to investigate potential new treatments for irritable bowel syndrome
Authors: Thompson Aiysha , Meah Dilruba , Ahmed Nadia , Conniff-Jenkins Rebecca , Chileshe Emma , Phillips Chris O , Claypole Tim C , Forman Dan W , Row Paula E
Published: November 2013

Background

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, which may result from alteration of the gastrointestinal microbiota following gastrointestinal infection, or with intestinal dysbiosis or small intestinal bacterial overgrowth. This may be treated with antibiotics, but there is concern that widespread antibiotic use might lead to antibiotic resistance. Some herbal medicines have been shown to be beneficial, but their mechanism(s) of action remain incompletely understood. To try to understand whether antibacterial properties might be involved in the efficacy of these herbal medicines, and to investigate potential new treatments for IBS, we have conducted a preliminary studyin vitroto compare the antibacterial activity of the essential oils of culinary and medicinal herbs against the bacterium,Esherichia coli.

Methods

Essential oils were tested for their ability to inhibitE. coligrowth in disc diffusion assays and in liquid culture, and to killE. coliin a zone of clearance assay. Extracts of coriander, lemon balm and spearmint leaves were tested for their antibacterial activity in the disc diffusion assay. Disc diffusion and zone of clearance assays were analysed by two-tailed t tests whereas ANOVA was performed for the turbidometric assays.

Results

Most of the oils exhibited antibacterial activity in all three assays, however peppermint, lemon balm and coriander seed oils were most potent, with peppermint and coriander seed oils being more potent than the antibiotic rifaximin in the disc diffusion assay. The compounds present in these oils were identified by gas chromatography mass spectrometry. Finally, extracts were made of spearmint, lemon balm and coriander leaves with various solvents and these were tested for their antibacterial activity againstE. coliin the disc diffusion assay.In each case, extracts made with ethanol and methanol exhibited potent antibacterial activity.

Conclusions

Many of the essential oils had antibacterial activity in the three assays, suggesting that they would be good candidates for testing in clinical trials. The observed antibacterial activity of ethanolic extracts of coriander, lemon balm and spearmint leaves suggests a mechanistic explanation for the efficacy of a mixture of coriander, lemon balm and mint extracts against IBS in a published clinical trial.
Containing the accidental laboratory escape of potential pandemic influenza viruses
Authors: Merler Stefano , Ajelli Marco , Fumanelli Laura , Vespignani Alessandro
Published: November 2013

Background

The recent work on the modified H5N1 has stirred an intense debate on the risk associated with the accidental release from biosafety laboratory of potential pandemic pathogens. Here, we assess the risk that the accidental escape of a novel transmissible influenza strain would not be contained in the local community.

Methods

We develop here a detailed agent-based model that specifically considers laboratory workers and their contacts in microsimulations of the epidemic onset. We consider the following non-pharmaceutical interventions: isolation of the laboratory, laboratory workers’ household quarantine, contact tracing of cases and subsequent household quarantine of identified secondary cases, and school and workplace closure both preventive and reactive.

Results

Model simulations suggest that there is a non-negligible probability (5% to 15%), strongly dependent on reproduction number and probability of developing clinical symptoms, that the escape event is not detected at all. We find that the containment depends on the timely implementation of non-pharmaceutical interventions and contact tracing and it may be effective (>90% probability per event) only for pathogens with moderate transmissibility (reproductive number no larger than R0 = 1.5). Containment depends on population density and structure as well, with a probability of giving rise to a global event that is three to five times lower in rural areas.

Conclusions

Results suggest that controllability of escape events is not guaranteed and, given the rapid increase of biosafety laboratories worldwide, this poses a serious threat to human health. Our findings may be relevant to policy makers when designing adequate preparedness plans and may have important implications for determining the location of new biosafety laboratories worldwide.
Inhibition of Tetrodotoxin-Resistant Sodium Current in Dorsal Root Ganglia Neurons Mediated by D1/D5 Dopamine Receptors
Authors: Galbavy William , Safaie Elham , Rebecchi Mario J , Puopolo Michelino
Published: November 2013

Background

Dopaminergic fibers originating from area A11 of the hypothalamus project to different levels of the spinal cord and represent the major source of dopamine. In addition, tyrosine hydroxylase, the rate-limiting enzyme for the synthesis of catecholamines, is expressed in 8–10% of dorsal root ganglia (DRG) neurons, suggesting that dopamine may be released in the dorsal root ganglia. Dopamine has been shown to modulate calcium current in DRG neurons, but the effects of dopamine on sodium current and on the firing properties of small DRG neurons are poorly understood.

Results

The effects of dopamine and dopamine receptor agonists were tested on the tetrodotoxin-resistant (TTX-R) sodium current recorded from acutely dissociated small (diameter ≤ 25 um) DRG neurons. Dopamine (20 μM) and SKF 81297 (10 μM) caused inhibition of TTX-R sodium current in small DRG neurons by 23% and 37%, respectively. In contrast, quinpirole (20 μM) had no effects on the TTX-R sodium current. Inhibition by SKF 81297 of the TTX-R sodium current was not affected when the protein kinase A (PKA) activity was blocked with the PKA inhibitory peptide (6-22), but was greatly reduced when the protein kinase C (PKC) activity was blocked with the PKC inhibitory peptide (19-36), suggesting that activation of D1/D5 dopamine receptors is linked to PKC activity. Expression of D1and D5 dopamine receptors in small DRG neurons, but not D2 dopamine receptors, was confirmed by Western blotting and immunofluorescence analysis. In current clamp experiments, the number of action potentials elicited in small DRG neurons by current injection was reduced by ˜ 30% by SKF 81297.

Conclusions

We conclude that activation of D1/D5 dopamine receptors inhibits TTX-R sodium current in unmyelinated nociceptive neurons and dampens their intrinsic excitability by reducing the number of action potentials in response to stimulus. Increasing or decreasing levels of dopamine in the dorsal root ganglia may serve to adjust the sensitivity of nociceptors to noxious stimuli.
Pharmacokinetics of piperacillin/tazobactam in cancer patients with hematological malignancies and febrile neutropenia after chemotherapy
Authors: Álvarez José C , Cuervo Sonia I , Garzón Javier R , Gómez Julio C , Díaz Jorge Augusto , Silva Edelberto , Sánchez Ricardo , Cortés Jorge A
Published: November 2013

Introduction

Patients with febrile neutropenia (FN) exhibit changes in extracellular fluid that may alter the plasma concentrations of beta-lactams and result in therapeutic failure or toxicity. We evaluated the pharmacokinetics of piperacillin/tazobactam in patients with hematological malignancies and FN after receiving chemotherapy at a primary public cancer center.

Methods

This was an open, nonrandomized, observational, descriptive, and prospective study. Samples from 15 patients with hematological malignancies and FN were evaluated after the administration of chemotherapy. Five blood samples were taken from each patient when the antibiotic level was at steady-state 10, 60, 120, 180, and 350 min after each dose. Antibiotic concentrations were measured using gel diffusion with Bacillus subtilis. All study participants provided written informed consent.

Results

We investigated the pharmacokinetics of piperacillin in 14 patients between the ages of 18 years and 59 years and with a mean absolute neutrophil count of 208 cells per mm3 (standard deviation (SD) ± 603.2). The following pharmacokinetic measurements were obtained: maximum concentration, 94.1–1133 mg/L; minimum concentration, 0.47–37.65 mg/L; volume of distribution, 0.08–0.65 L/kg (mean, 0.34 L/kg); drug clearance (CL), 4.42–27.25 L/h (mean, 9.93 L/h); half-life (t1/2), 0.55–2.65 h (mean, 1.38 h); and area under the curve, 115.12–827.16 mg · h/L.

Conclusion

Patients with FN after receiving chemotherapy exhibited significant variations in the pharmacokinetic parameters of piperacillin compared with healthy individuals; specifically, FN patients demonstrated an increase in t1/2 and decreased CL.
Evidence that TNF-β (lymphotoxin α) can activate the inflammatory environment in human chondrocytes
Authors: Buhrmann Constanze , Shayan Parviz , Aggarwal Bharat B , Shakibaei Mehdi
Published: November 2013

Introduction

Inflammatory cytokines play a key role in the pathogenesis of joint diseases such as rheumatoid arthritis (RA). Current therapies target mainly tumor necrosis factor α (TNF-α) as this has proven benefits. However, a large number of patients do not respond to or become resistant to anti-TNF-α therapy. While the role of TNF-α in RA is quite evident, the role of TNF-β, also called lymphotoxin-α (LT-α), is unclear. In this study we investigated whether TNF-β and its receptor play a role in chondrocytes in the inflammatory environment.

Methods

An in vitro model of primary human chondrocytes was used to study TNF-β-mediated inflammatory signaling.

Results

Cytokine-induced inflammation enhances TNF-β and TNF-β-receptor expression in primary human chondrocytes accompanied by the up-regulation of inflammatory (cyclooxygenase-2), matrix degrading (matrix metalloproteinase-9 and -13) and apoptotic (p53, cleaved caspase-3) signaling pathways, all known to be regulated by NF-κB. In contrast, anti-TNF-β, similar to the natural NF-κB inhibitor (curcumin, diferuloylmethane) or the knockdown of NF-κB by using antisense oligonucleotides (ASO), suppressed IL-1β-induced NF-κB activation and its translocation to the nucleus, and abolished the pro-inflammatory and apoptotic effects of IL-1β. This highlights, at least in part, the crucial role of NF-κB in TNF-β-induced-inflammation in cartilage, similar to that expected for TNF-α. Finally, the adhesiveness between TNF-β-expressing T-lymphocytes and the responding chondrocytes was significantly enhanced through a TNF-β-induced inflammatory microenvironment.

Conclusions

These results suggest for the first time that TNF-β is involved in microenvironment inflammation in chondrocytes during RA parallel to TNF-α, resulting in the up-regulation of NF-κB signaling and activation of pro-inflammatory activity.
Single-cell genomics reveal low recombination frequencies in freshwater bacteria of the SAR11 clade
Authors: Zaremba-Niedzwiedzka Katarzyna , Viklund Johan , Zhao Weizhou , Ast Jennifer , Sczyrba Alexander , Woyke Tanja , McMahon Katherina , Bertilsson Stefan , Stepanauskas Ramunas , Andersson Siv G E
Published: November 2013

Background

The SAR11 group of Alphaproteobacteria is highly abundant in the oceans. It contains a recently diverged freshwater clade, which offers the opportunity to compare adaptations to salt- and freshwaters in a monophyletic bacterial group. However, there are no cultivated members of the freshwater SAR11 group and no genomes have been sequenced yet.

Results

We isolated ten single SAR11 cells from three freshwater lakes and sequenced and assembled their genomes. A phylogeny based on 57 proteins indicates that the cells are organized into distinct microclusters. We show that the freshwater genomes have evolved primarily by the accumulation of nucleotide substitutions and that they have among the lowest ratio of recombination to mutation estimated for bacteria. In contrast, members of the marine SAR11 clade have one of the highest ratios. Additional metagenome reads from six lakes confirm low recombination frequencies for the genome overall and reveal lake-specific variations in microcluster abundances. We identify hypervariable regions with gene contents broadly similar to those in the hypervariable regions of the marine isolates, containing genes putatively coding for cell surface molecules.

Conclusions

We conclude that recombination rates differ dramatically in phylogenetic sister groups of the SAR11 clade adapted to freshwater and marine ecosystems. The results suggest that the transition from marine to freshwater systems has purged diversity and resulted in reduced opportunities for recombination with divergent members of the clade. The low recombination frequencies of the LD12 clade resemble the low genetic divergence of host-restricted pathogens that have recently shifted to a new host.
Vitamin D Is a Regulator of Endothelial Nitric Oxide Synthase and Arterial Stiffness in Mice
Authors: Andrukhova Olena , Slavic Svetlana , Zeitz Ute , Riesen Sabine C. , Heppelmann Monika S. , Ambrisko Tamas D. , Markovic Mato , Kuebler Wolfgang M. , Erben Reinhold G.
Published: November 2013

The vitamin D hormone 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] is essential for the preservation of serum calcium and phosphate levels but may also be important for the regulation of cardiovascular function. Epidemiological data in humans have shown that vitamin D insufficiency is associated with hypertension, left ventricular hypertrophy, increased arterial stiffness, and endothelial dysfunction in normal subjects and in patients with chronic kidney disease and type 2 diabetes. However, the pathophysiological mechanisms underlying these associations remain largely unexplained. In this study, we aimed to decipher the mechanisms by which 1,25(OH)2D3 may regulate systemic vascular tone and cardiac function, using mice carrying a mutant, functionally inactive vitamin D receptor (VDR). To normalize calcium homeostasis in VDR mutant mice, we fed the mice lifelong with the so-called rescue diet enriched with calcium, phosphate, and lactose. Here, we report that VDR mutant mice are characterized by lower bioavailability of the vasodilator nitric oxide (NO) due to reduced expression of the key NO synthesizing enzyme, endothelial NO synthase, leading to endothelial dysfunction, increased arterial stiffness, increased aortic impedance, structural remodeling of the aorta, and impaired systolic and diastolic heart function at later ages, independent of changes in the renin-angiotensin system. We further demonstrate that 1,25(OH)2D3 is a direct transcriptional regulator of endothelial NO synthase. Our data demonstrate the importance of intact VDR signaling in the preservation of vascular function and may provide a mechanistic explanation for epidemiological data in humans showing that vitamin D insufficiency is associated with hypertension and endothelial dysfunction.
Dynamic Postnatal Developmental and Sex-Specific Neuroendocrine Effects of Prenatal Polychlorinated Biphenyls in rats
Authors: Walker Deena M. , Goetz Benjamin M. , Gore Andrea C.
Published: November 2013

Gestational exposures to estrogenic compounds, both endogenous hormones and exogenous endocrine-disrupting chemicals (EDCs), have long-term effects on reproductive physiology and behavior. We tested the hypothesis that prenatal treatment of rats with low doses of Aroclor 1221 (A1221), a weakly estrogenic polychlorinated biphenyl mix previously used in industry, or estradiol benzoate (EB), alters development of the hypothalamus in a sexually dimorphic manner and subsequently perturbs reproductive function. Pregnant Sprague-Dawley rats were injected on embryonic days 16 and 18 with vehicle (dimethylsulfoxide), A1221 (1 mg/kg), or EB (50 μg/kg). Developmental milestones were monitored, and on postnatal days 15, 30, 45, and 90, 1 male and 1 female per litter were euthanized. Because of their key roles in the mediation of steroid actions on reproductive function, the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (ARC) were punched for a low-density quantitative PCR array of 48 neuroendocrine genes and analysis of DNA methylation of a subset of genes. Gestational exposure to A1221 or EB delayed the timing of puberty in males and disrupted estrous cyclicity in females. In the AVPV, 28 genes were affected by treatment in a developmental stage–specific manner, mostly in females, which exhibited a masculinized expression profile. This included 2 clock genes, Per2 and Arntl, implicating circadian circuits as being vulnerable to endocrine disruption. DNA methylation analysis of 2 genes, Per2 and Ar, showed no effect of EDCs and suggested alternative mechanisms for the altered mRNA levels. In the ARC, 12 genes were affected by treatment, mostly in males, again with dynamic developmental changes. Bionetwork analysis of relationships among genes, hormones, and physiological markers showed sexually dimorphic effects of estrogenic EDC exposures, with the female AVPV and the male ARC being most vulnerable, and provided novel relationships among hypothalamic genes and postnatal reproductive maturation.
Function of theDrosophilareceptor guanylyl cyclase Gyc76C in PlexA-mediated motor axon guidance
Authors: Chak Kayam , Kolodkin Alex L.
Published: November 2013

The second messengers cAMP and cGMP modulate attraction and repulsion mediated by neuronal guidance cues. We find that the Drosophila receptor guanylyl cyclase Gyc76C genetically interacts with Semaphorin 1a (Sema-1a) and physically associates with the Sema-1a receptor plexin A (PlexA). PlexA regulates Gyc76C catalytic activity in vitro, and each distinct Gyc76C protein domain is crucial for regulating Gyc76C activity in vitro and motor axon guidance in vivo. The cytosolic protein dGIPC interacts with Gyc76C and facilitates Sema-1a-PlexA/Gyc76C-mediated motor axon guidance. These findings provide an in vivo link between semaphorin-mediated repulsive axon guidance and alteration of intracellular neuronal cGMP levels.
Meis2 is a Pax6 co-factor in neurogenesis and dopaminergic periglomerular fate specification in the adult olfactory bulb
Authors: Agoston Zsuzsa , Heine Peer , Brill Monika S. , Grebbin Britta Moyo , Hau Ann-Christin , Kallenborn-Gerhardt Wiebke , Schramm Jasmine , Götz Magdalena , Schulte Dorothea
Published: November 2013

Meis homeodomain transcription factors control cell proliferation, cell fate specification and differentiation in development and disease. Previous studies have largely focused on Meis contribution to the development of non-neuronal tissues. By contrast, Meis function in the brain is not well understood. Here, we provide evidence for a dual role of the Meis family protein Meis2 in adult olfactory bulb (OB) neurogenesis. Meis2 is strongly expressed in neuroblasts of the subventricular zone (SVZ) and rostral migratory stream (RMS) and in some of the OB interneurons that are continuously replaced during adult life. Targeted manipulations with retroviral vectors expressing function-blocking forms or with small interfering RNAs demonstrated that Meis activity is cell-autonomously required for the acquisition of a general neuronal fate by SVZ-derived progenitors in vivo and in vitro. Additionally, Meis2 activity in the RMS is important for the generation of dopaminergic periglomerular neurons in the OB. Chromatin immunoprecipitation identified doublecortin and tyrosine hydroxylase as direct Meis targets in newly generated neurons and the OB, respectively. Furthermore, biochemical analyses revealed a previously unrecognized complex of Meis2 with Pax6 and Dlx2, two transcription factors involved in OB neurogenesis. The full pro-neurogenic activity of Pax6 in SVZ derived neural stem and progenitor cells requires the presence of Meis. Collectively, these results show that Meis2 cooperates with Pax6 in generic neurogenesis and dopaminergic fate specification in the adult SVZ-OB system.
Induction of endocycles represses apoptosis independently of differentiation and predisposes cells to genome instability
Authors: Hassel Christiane , Zhang Bingqing , Dixon Michael , Calvi Brian R.
Published: November 2013

The endocycle is a common developmental cell cycle variation wherein cells become polyploid through repeated genome duplication without mitosis. We previously showed that Drosophila endocycling cells repress the apoptotic cell death response to genotoxic stress. Here, we investigate whether it is differentiation or endocycle remodeling that promotes apoptotic repression. We find that when nurse and follicle cells switch into endocycles during oogenesis they repress the apoptotic response to DNA damage caused by ionizing radiation, and that this repression has been conserved in the genus Drosophila over 40 million years of evolution. Follicle cells defective for Notch signaling failed to switch into endocycles or differentiate and remained apoptotic competent. However, genetic ablation of mitosis by knockdown of Cyclin A or overexpression of fzr/Cdh1 induced follicle cell endocycles and repressed apoptosis independently of Notch signaling and differentiation. Cells recovering from these induced endocycles regained apoptotic competence, showing that repression is reversible. Recovery from fzr/Cdh1 overexpression also resulted in an error-prone mitosis with amplified centrosomes and high levels of chromosome loss and fragmentation. Our results reveal an unanticipated link between endocycles and the repression of apoptosis, with broader implications for how endocycles may contribute to genome instability and oncogenesis.
GABA suppresses neurogenesis in the adult hippocampus through GABAB receptors
Authors: Giachino Claudio , Barz Michael , Tchorz Jan S. , Tome Mercedes , Gassmann Martin , Bischofberger Josef , Bettler Bernhard , Taylor Verdon
Published: November 2013

Adult neurogenesis is tightly regulated through the interaction of neural stem/progenitor cells (NSCs) with their niche. Neurotransmitters, including GABA activation of GABAA receptor ion channels, are important niche signals. We show that adult mouse hippocampal NSCs and their progeny express metabotropic GABAB receptors. Pharmacological inhibition of GABAB receptors stimulated NSC proliferation and genetic deletion of GABAB1 receptor subunits increased NSC proliferation and differentiation of neuroblasts in vivo. Cell-specific conditional deletion of GABAB receptors supports a cell-autonomous role in newly generated cells. Our data indicate that signaling through GABAB receptors is an inhibitor of adult neurogenesis.
Cullin5 destabilizes Cas to inhibit Src-dependent cell transformation
Authors: Teckchandani Anjali , Laszlo George S. , Simó Sergi , Shah Khyati , Pilling Carissa , Strait Alexander A. , Cooper Jonathan A.
Published: November 2013

Phosphorylation-dependent protein ubiquitylation and degradation provides an irreversible mechanism to terminate protein kinase signaling. Here we report that mammary epithelial cells require Cullin 5 RING E3 ubiquitin ligase complexes (Cul5-CRLs) to prevent transformation by a Src-Cas signaling pathway. Removing Cul5 stimulates growth factor-independent growth and migration, membrane dynamics, and colony dysmorphogenesis, dependent on the endogenous tyrosine kinase, Src. Src is activated in Cul5-deficient cells, but Src activation alone is not sufficient to cause transformation. We found that Cul5 and Src together stimulate degradation of the Src substrate, p130Cas (Crk-associated substrate). Phosphorylation stimulates Cas binding to the Cul5-CRL adaptor protein SOCS6 and consequent proteasome-dependent degradation. Cas is necessary for the transformation of Cul5-deficient cells. Either SOCS6 knockdown or a degradation-resistant Cas mutant stimulates membrane ruffling but not other aspects of transformation. Our results show that endogenous Cul5 suppresses epithelial cell transformation by several pathways, including inhibiting Src-Cas-induced ruffling through SOCS6.
Frs2α and Shp2 signal independently of Gab to mediate FGF signaling in lens development
Authors: Li Hongge , Tao Chenqi , Cai Zhigang , Hertzler-Schaefer Kristina , Collins Tamica N. , Wang Fen , Feng Gen-Sheng , Gotoh Noriko , Zhang Xin
Published: November 2013

FGF signaling requires a plethora of adaptor proteins to elicit downstream responses, but the functional significances of these docking proteins remain controversial. In this study, we used lens development as a model to investigate Frs2α and its structurally related scaffolding protein Gab1 and Gab2 in FGF signaling. We show that genetic ablation of Frs2α alone has modest effect, but additional deletion of tyrosine phosphatase Shp2 causes a complete arrest of lens vesicle development. Biochemical evidence suggests that this Frs2α-Shp2 synergy reflects their epistatic relationship in FGF signaling cascade, as opposed to compensatory or parallel functions of these two proteins. Genetic interaction experiments further demonstrate that direct binding of Shp2 to Frs2α is necessary for activating ERK signaling, while constitutive activation of either Shp2 or Kras signaling can compensate for the absence of Frs2α in lens development. In contrast, knockouts of Gab1 and Gab2 failed to disrupt FGF signaling in vitro and lens development in vivo. These results establish Frs2α-Shp2 complex as the key mediator of FGF signaling in lens development.
The molecular basis for selective assembly of the UBAP1-containing, endosome-specific ESCRT-I complex
Authors: Wunderley Lydia , Brownhill Kim , Stefani Flavia , Tabernero Lydia , Woodman Philip
Published: November 2013

ESCRT-I is essential for the multivesicular body (MVB) sorting of ubiquitinated cargo such as epidermal growth factor receptor, as well as for divergent cellular functions such as cell division and retroviral budding. ESCRT-I has four subunits; TSG101, VPS28, VPS37 and MVB12. There are several members of VPS37 and MVB12 families in mammalian cells, and their differential incorporation into ESCRT-I could provide function-specific variants of the complex. However, it remains unclear whether these different forms of VPS37 and MVB12 combine randomly or generate selective pairings within ESCRT-I, and what the mechanistic basis for such pairing would be. Here we show that the incorporation into ESCRT-I of two MVB12 members, UBAP1 and MVB12A, is highly selective with respect to their VPS37 partners. We map the selective assembly of UBAP1/VPS37A to the core ESCRT-I binding domain of VPS37A. In contrast, selective integration of UBAP1 requires both the minimal ESCRT-I binding region and a neighbouring predicted helix. The biochemical specificity in ESCRT-I assembly is matched by functional specialisation, since siRNA-mediated depletion of UBAP1, but not MVB12A or MVB12B, disrupts ubiquitin-dependent sorting at the MVB.
Metal–Carbon Bonds in Biopolymer Conjugates: Bioorganometallic Nucleic Acid Chemistry
Authors: Duprey Jean-Louis H A , Tucker James H R
Published: November 2013

This review summarizes the field of bioorganometallic nucleic acid chemistry, with a specific focus on various synthetic approaches for utilizing organometallic groups, in particular ferrocene, as functional tags for existing nucleic acids or as components for novel nucleic acid analogues.
Stereochemical Communication within Tetrahedral Capsules
Authors: Castilla Ana M , Ramsay William J , Nitschke Jonathan R
Published: November 2013

The creation of isolated chirotopic environments that mimic enzyme binding pockets has been a long-term goal in supramolecular chemistry. Metal–organic cages with enclosed and defined inner spaces have proven useful for this purpose. Here, we provide a review of recent progress on understanding, and controlling the transmission of stereochemistry within [M4(L)6] and [M4(L)4] tetrahedral cages.
Personnel Policy and Personnel Management as Factors of Russia's Modernization
Authors: Турчинов  , Turchinov Alyeksandr
Published: November 2013

The article deals with current problems of management

theory and practice devoted to personnel policy, personnel management

in the context of the modernization of society, as well as risks, challenges

and threats to human resources of an organization and the state under

the conditions of a globalizing world.
To the questionon on the management of intellectual resources
Authors: Слезко  , Slezko Vyacheslav
Published: November 2013

The article deals with the evolution of the development of

intellectual resources. Shows the notions of intellectual property and intellectual

capital, which creates a theoretical basis for the formation of the

effective mechanism of management of intellectual resources.