bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Upgrading and Labour in Global Production Networks: A Critique and an Alternative Conception
Authors: Selwyn Ben
Published: February 2013

Over the last two decades the global commodity chain, global value chain and global production network (GCC/GVC/GPN) frameworks have facilitated valuable research into contemporary global capitalism. However, much of this research has paid insufficient attention to work and workers. Recently, the concept of social upgrading, with a strong emphasis on workers' conditions, has been advanced by leading GCC/GVC/GPN theorists, as a potential remedy to the previous lacunae. This article welcomes this development, but also argues that the social upgrading concept represents an elite comprehension of relations between capital, the state and labour. It is argued that the concept, derived from the International Labour Organization's Decent Work Agenda, denies the reality of labour's exploitation by capital and is therefore only partially equipped to explain the existence of indecent work. The Decent Work Agenda and the social upgrading concept expect improvements in work to be delivered by elite actors such as firms, national states and international organizations. It is argued that, through re-visiting Marx's explication of the capitalist labour process, it is possible to comprehend the nature of capitalist exploitation, the root causes of indecent work and resistance to it, and thus to develop an alternative conception of social upgrading. The article presents evidence from North East Brazilian export horticulture to support these arguments.
International Supply Chains and the Labour Process
Authors: Robinson Pamela K. , Rainbird Helen
Published: February 2013

The changing nature of global production and distribution processes and their impact on the capital–labour relationship raise a number of questions for labour process analysis. Where business operates across national boundaries whether as multinational companies (MNCs) or as lead firms in international supply chains, the relational nature of power relationships between and within firms is significant to understanding the bargaining power of labour at the point of production (Coe et al., 2008a). Although there is no single body of theory relating to the analysis of international supply chains, the article argues that the perspectives developed by different authors relating to global commodity chains (GCCs), global value chains (GVCs) and global production networks (GPNs) have a contribution to make to labour process analysis. This contribution lies in the understanding of the contested nature of systems of managerial control, on the one hand, and the sources of resistance and ability of labour to mobilize, on the other.
European Gender Archaeologies in Historical Perspective
Authors: Dommasnes Liv Helga , Montón-Subías Sandra
Published: February 2013

This study presents an overview of the development of gender archaeologies in local academies across Europe, from the initial efforts in Norway in the early 1970s, to the founding of the multinational Archaeology and Gender in Europe (AGE) working group in 2009. In addition, the study seeks to show the scope of gender archaeology once contributions from different traditions in different languages are included, and to provide comparative historiographies for those European countries where gender archaeology is now a major strand of research. We hope that innovative approaches to the study of gender in the past will emerge in the future thanks to fruitful encounters between regional trends and developments.
On Mann-type iteration method for a family of hemicontractive mappings in Hilbert spaces
Authors: Hussain Nawab , Ćirić Ljubomir B , Cho Yeol Je , Rafiq Arif
Published: February 2013

Let K be a compact convex subset of a real Hilbert space H and

T
i

:
K
→
K

,

i
=
1
,
2
,
…
,
k

, be a family of continuous hemicontractive mappings. Let

α
n

,

β
n
i

∈
[
0
,
1
]

be such that

α
n

+

∑

i
=
1

k

β
n
i

=
1

and satisfying

{

α
n

}
,

β
n
i

⊂
[
δ
,
1
−
δ
]

for some

δ
∈
(
0
,
1
)

,

i
=
1
,
2
,
…
,
k

. For arbitrary

x
0

∈
K

, define the sequence

{

x
n

}

by (1.9) see below, then

{

x
n

}

converges strongly to a common fixed point in

⋂

i
=
1

k

F
(

T
i

)
≠
∅

.

MSC:05C38, 15A15, 05A15, 15A18.
An integrated approach to characterize transcription factor and microRNA regulatory networks involved in Schwann cell response to peripheral nerve injury
Authors: Chang Li-Wei , Viader Andreu , Varghese Nobish , Payton Jacqueline E , Milbrandt Jeffrey , Nagarajan Rakesh
Published: February 2013

Background

The regenerative response of Schwann cells after peripheral nerve injury is a critical process directly related to the pathophysiology of a number of neurodegenerative diseases. This SC injury response is dependent on an intricate gene regulatory program coordinated by a number of transcription factors and microRNAs, but the interactions among them remain largely unknown. Uncovering the transcriptional and post-transcriptional regulatory networks governing the Schwann cell injury response is a key step towards a better understanding of Schwann cell biology and may help develop novel therapies for related diseases. Performing such comprehensive network analysis requires systematic bioinformatics methods to integrate multiple genomic datasets.

Results

In this study we present a computational pipeline to infer transcription factor and microRNA regulatory networks. Our approach combined mRNA and microRNA expression profiling data, ChIP-Seq data of transcription factors, and computational transcription factor and microRNA target prediction. Using mRNA and microRNA expression data collected in a Schwann cell injury model, we constructed a regulatory network and studied regulatory pathways involved in Schwann cell response to injury. Furthermore, we analyzed network motifs and obtained insights on cooperative regulation of transcription factors and microRNAs in Schwann cell injury recovery.

Conclusions

This work demonstrates a systematic method for gene regulatory network inference that may be used to gain new information on gene regulation by transcription factors and microRNAs.
Sulphur limitation provokes physiological and leaf proteome changes in oilseed rape that lead to perturbation of sulphur, carbon and oxidative metabolisms
Authors: D’Hooghe Philippe , Escamez Sacha , Trouverie Jacques , Avice Jean-Christophe
Published: February 2013

Background

The decline in industrial emissions of sulphur (S) has led to a sulphate depletion in soil resulting in an alteration of crop performance. In oilseed rape, an S deficiency dramatically reduced the seed yield and/or quality. Paradoxically, little is known about the impact of sulphate limitation on oilseed rape leaf metabolism, despite it being a key determinant of growth. In order to identify the metabolic processes involved in the oilseed rape response to S restriction, an analysis of the young leaf proteome combined with a physiological study was carried out at the vegetative stage.

Results

S limitation does not significantly reduce the total shoot biomass but inhibits growth and photosynthesis of young leaves. This photosynthesis decline is not due to a decrease in chlorophyll content, which remains similar to Control. The increase in anthocyanins and H2O2 content in young leaves of S-limited plants suggests that S restriction leads to an oxidative stress. Proteomic analysis at 35 d of S limitation also revealed the induction of 12-oxophitodienoate reductase and ACC synthase, respectively involved in jasmonate and ethylene biosynthesis, two phytohormones that could be implicated in oxidative stress. Proteins involved in photosynthesis and carbon metabolism were also modulated by S restriction. In particular, the decrease in plastocyanin and ferredoxin–NADP reductase suggests that H2O2 accumulation is associated with perturbation of the photosynthetic electron transport chain. The accumulation of chloroplastic Cu-Zn SOD reinforces the idea that an oxidative stress probably occurs in the chloroplast. Proteomic results suggest that the maintenance of chlorophyll in S-limited conditions is related to an accumulation of Water Soluble Chlorophyll binding Proteins, involved in the protection of chlorophyll against ROS. The accumulation of the catalytic α–subunit of chloroplastic ATP synthase suggests that energy production is maintained.

Conclusion

S limitation leads to photosynthesis and carbon metabolism disturbances that could be responsible for the oxidative stress observed in the young leaves of oilseed rape. Despite this, induction of proteins involved in oxidative stress resistance and energy production shows that the leaf capacity to capture and use photosynthetic active radiations for ATP production remains efficient for as long as possible.
Healthcare workers and prevention of hepatitis C virus transmission: exploring knowledge, attitudes and evidence-based practices in hemodialysis units in Italy
Authors: Bianco Aida , Bova Francesca , Nobile Carmelo GA , Pileggi Claudia , Pavia Maria ,   The Collaborative Working Group
Published: February 2013

Background

Evidence exists regarding the full prevention of HCV transmission to hemodialysis patients by implementing universal precaution. However, little information is available regarding the frequency with which hospitals have adopted evidence-based practices for preventing HCV infection among hemodialysis patients. A cross-sectional survey has been conducted among nurses in Calabria region (Italy) in order to acquire information about the level of knowledge, the attitudes and the frequencies of evidence-based practices that prevent hospital transmission of HCV.

Methods

All 37 hemodialysis units (HDU) of Calabria were included in the study and all nurses were invited to participate in the study and to fill in a self-administered questionnaire.

Results

90% of the nurses working in HDU participated in the study. Correct answers about HCV pattern of transmission ranged from 73.7% to 99.3% and were significantly higher in respondents who knew that isolation of HCV-infected patients is not recommended and among those who knew that previous bloodstream infections should be included in medical record and among nurses with fewer years of practice. Most correctly thought that evidence-based infection control measures provide adequate protection against transmission of bloodborne pathogens among healthcare workers. Positive attitude was significantly higher among more knowledgeable nurses. Self-reporting of appropriate handwashing procedures were significantly more likely in nurses who were aware that transmission of bloodborne pathogens among healthcare workers may be prevented through adoption of evidence-based practices and with a correct knowledge about HCV transmission patterns.

Conclusions

Behavior changes should be aimed at abandoning outdated practices and adopting and maintaining evidence-based practices. Initiatives focused at enabling and reinforcing adherence to effective prevention practices among nurses in HDU are strongly needed.
Finding an alternative diagnosis does not justify increased use of CT-pulmonary angiography
Authors: Chandra Subani , Sarkar Pralay K , Chandra Divay , Ginsberg Nicole E , Cohen Rubin I
Published: February 2013

Background

The increased use of computed tomography pulmonary angiography (CTPA) is often justified by finding alternative diagnoses explaining patients’ symptoms. However, this has not been rigorously examined.

Methods

We retrospectively reviewed CTPA done at our center over an eleven year period (2000 – 2010) in patients with suspected pulmonary embolus (PE). We then reviewed in detail the medical records of a representative sample of patients in three index years – 2000, 2005 and 2008. We determined whether CTPA revealed pulmonary pathology other than PE that was not readily identifiable from the patient’s history, physical examination and prior chest X-ray. We also assessed whether the use of pre-test probability guided diagnostic strategy for PE.

Results

A total of 12,640 CTPA were performed at our center from year 2000 to 2010. The number of CTPA performed increased from 84 in 2000 to 2287 in 2010, a 27 fold increase. Only 7.6 percent of all CTPA and 3.2 percent of avoidable CTPAs (low or intermediate pre-test probability and negative D-dimer) revealed previously unknown findings of any clinical significance. When we compared 2008 to 2000 and 2005, more CTPAs were performed in younger patients (mean age (years) for 2000: 67, 2005: 63, and 2008: 60, (p=0.004, one–way ANOVA)). Patients were less acutely ill with fewer risk factors for PE. Assessment of pre-test probability of PE and D-dimer measurement were rarely used to select appropriate patients for CTPA (pre-test probability of PE documented in chart (% total) in year 2000: 4.1%, 2005: 1.6%, 2008: 3.1%).

Conclusions

Our data do not support the argument that increased CTPA use is justified by finding an alternative pulmonary pathology that could explain patients’ symptoms. CTPA is being increasingly used as the first and only test for suspected PE.
The effect of indomethacin on the muscarinic induced contractions in the isolated normal guinea pig urinary bladder
Authors: Rahnama’i Mohammad S , van Koeveringe Gommert A , van Kerrebroeck Philip EV , de Wachter Stefan GG
Published: February 2013

Background

To investigate the effect of prostaglandin depletion by means of COX-inhibition on cholinergic enhanced spontaneous contractions.

Methods

The urethra and bladder of 9 male guinea pigs (weight 270–300 g) were removed and placed in an organ bath with Krebs’ solution. A catheter was passed through the urethra through which the intravesical pressure was measured. The muscarinic agonist arecaidine, the non-selective COX inhibitor indomethacin, and PGE2 were subsequently added to the organ bath. The initial average frequency and amplitude of spontaneous contractions in the first 2 minutes after arecaidine application were labelled Fini and Pini, respectively. The steady state frequency (Fsteady) and amplitude (Psteady) were defined as the average frequency and amplitude during the 5 minutes before the next wash out.

Results

Application of 1 μM PGE2 increased the amplitude of spontaneous contractions without affecting frequency. 10 μM of indomethacin reduced amplitude but not frequency.

The addition of indomethacin did not alter Fini after the first application (p = 0.7665). However, after the second wash, Fini was decreased (p = 0.0005). Fsteady, Psteady and Pini were not significantly different in any of the conditions. These effects of indomethacin were reversible by PGE2 addition..

Conclusions

Blocking PG synthesis decreased the cholinergically stimulated autonomous contractions in the isolated bladder. This suggests that PG could modify normal cholinergically evoked response. A combination of drugs inhibiting muscarinic receptors and PG function or production can then become an interesting focus of research on a treatment for overactive bladder syndrome.
Bacterial inclusion bodies as potential synthetic devices for pathogen recognition and a therapeutic substance release
Authors: Talafová Klaudia , Hrabárová Eva , Chorvát Dušan , Nahálka Jozef
Published: February 2013

Background

Adhesins of pathogens recognise the glycans on the host cell and mediate adherence. They are also crucial for determining the tissue preferences of pathogens. Currently, glyco-nanomaterials provide potential tool for antimicrobial therapy. We demonstrate that properly glyco-tailored inclusion bodies can specifically bind pathogen adhesins and release therapeutic substances.

Results

In this paper, we describe the preparation of tailored inclusion bodies via the conjugation of indicator protein aggregated to form inclusion bodies with soluble proteins. Whereas the indicator protein represents a remedy, the soluble proteins play a role in pathogen recognition. For conjugation, glutaraldehyde was used as linker. The treatment of conjugates with polar lysine, which was used to inactivate the residual glutaraldehyde, inhibited unwanted hydrophobic interactions between inclusion bodies. The tailored inclusion bodies specifically interacted with the SabA adhesin from Helicobacter pylori aggregated to form inclusion bodies that were bound to the sialic acids decorating the surface of human erythrocytes. We also tested the release of indicator proteins from the inclusion bodies using sortase A and Ssp DNAB intein self-cleaving modules, respectively. Sortase A released proteins in a relatively short period of time, whereas the intein cleavage took several weeks.

Conclusions

The tailored inclusion bodies are promising “nanopills” for biomedical applications. They are able to specifically target the pathogen, while a self-cleaving module releases a soluble remedy. Various self-cleaving modules can be enabled to achieve the diverse pace of remedy release.
Abdominal adiposity is the main determinant of the C-reactive response to injury in subjects undergoing inguinal hernia repair
Authors: Irkulla Sashidhar , Ujam Bedri , Gaze David , Kumar Devinder , Mendall Michael A
Published: February 2013

Background

Obesity and serum C-reactive protein (CRP) (a sensitive marker of inflammatory activity) are associated with most chronic diseases. Abdominal adiposity along with age is the strongest determinant of baseline CRP levels in healthy subjects. The mechanism of the association of serum CRP with disease is uncertain. We hypothesized that baseline serum CRP is a marker of inflammatory responsiveness to injury and that abdominal adiposity is the main determinant of this responsiveness. We studied the effect of abdominal adiposity, age and other environmental risk factors for chronic disease on the CRP response to a standardised surgical insult, unilateral hernia repair to not only test this hypothesis but to inform the factors which must be taken into account when assessing systemic inflammatory responses to surgery.

Methods

102 male subjects aged 24-94 underwent unilateral hernia repair by a single operator. CRP was measured at 0, 6, 24 and 48 hrs. Response was defined as the peak CRP adjusted for baseline CRP.

Results

Age and waist:hip ratio (WHR) were associated both with basal CRP and CRP response with similar effect sizes after adjustment for a wide-range of covariates. The adjusted proportional difference in CRP response per 10% increase in WHR was 1.50 (1.17-1.91) p = 0.0014 and 1.15(1.00-1.31) p = 0.05 per decade increase in age. There was no evidence of important effects of other environmental cardiovascular risk factors on CRP response.

Conclusion

Waist:hip ratio and age need to be considered when studying the inflammatory response to surgery. The finding that age and waist:hip ratio influence baseline and post-operative CRP levels to a similar extent suggests that baseline CRP is a measure of inflammatory responsiveness to casual stimuli and that higher age and obesity modulate the generic excitability of the inflammatory system leading to both higher baseline CRP and higher CRP response to surgery. The mechanism for the association of baseline CRP and waist:hip ratio to chronic disease outcomes could be through this increase in inflammatory system excitability.
The number and type of food retailers surrounding schools and their association with lunchtime eating behaviours in students
Authors: Seliske Laura , Pickett William , Rosu Andrei , Janssen Ian
Published: February 2013

Background

The primary study objective was to examine whether the presence of food retailers surrounding schools was associated with students’ lunchtime eating behaviours. The secondary objective was to determine whether measures of the food retail environment around schools captured using road network or circular buffers were more strongly related to eating behaviours while at school.

Methods

Grade 9 and 10 students (N=6,971) who participated in the 2009/10 Canadian Health Behaviour in School Aged Children Survey were included in this study. The outcome was determined by students’ self-reports of where they typically ate their lunch during school days. Circular and road network-based buffers were created for a 1 km distance surrounding 158 schools participating in the HBSC. The addresses of fast food restaurants, convenience stores and coffee/donut shops were mapped within the buffers. Multilevel logistic regression was used to determine whether there was a relationship between the presence of food retailers near schools and students regularly eating their lunch at a fast food restaurant, snack-bar or café. The Akaike Information Criteria (AIC) value, a measure of goodness-of-fit, was used to determine the optimal buffer type.

Results

For the 1 km circular buffers, students with 1–2 (OR= 1.10, 95% CI: 0.57-2.11), 3–4 (OR=1.45, 95% CI: 0.75-2.82) and ≥5 nearby food retailers (OR=2.94, 95% CI: 1.71-5.09) were more likely to eat lunch at a food retailer compared to students with no nearby food retailers. The relationships were slightly stronger when assessed via 1 km road network buffers, with a greater likelihood of eating at a food retailer for 1–2 (OR=1.20, 95% CI:0.74-1.95), 3–4 (OR=3.19, 95% CI: 1.66-6.13) and ≥5 nearby food retailers (OR=3.54, 95% CI: 2.08-6.02). Road network buffers appeared to provide a better measure of the food retail environment, as indicated by a lower AIC value (3332 vs. 3346).

Conclusions

There was a strong relationship between the presence of food retailers near schools and students’ lunchtime eating behaviours. Results from the goodness of fit analysis suggests that road network buffers provide a more optimal measure of school neighbourhood food environments relative to circular buffers.
Self-assembled monolayers of pyridylthio-functionalized carbon nanotubes used as a support to immobilize cytochrome c
Authors: Sun Qing , Liu Jiang , Huang Hong-Xiang , Chen Meng , Qian Dong-Jin
Published: February 2013

Self-assembled monolayers (SAMs) of pyridylthio-functionalized multiwalled carbon nanotubes (pythio-MWNTs) have been constructed on the gold substrate surface, which were used as a support to immobilize cytochrome c (Cyt c). The assembly processes of the SAMs and adsorption of Cyt c were monitored by using quartz crystal microbalance (QCM). Based on the frequency change of the QCM resonator, the surface coverage for the SAMs of pythio-MWNTs was estimated to be about 5.2 μg/cm2, and that of the Cyt c adsorbed was about 0.29 μg/cm2. For the gold electrode modified by the SAMs of pythio-MWNTs-Cyt c, a quasi-reversible redox wave was recorded with the cathodic and anodic potentials at about −0.55 and −0.28 V vs Ag/AgCl, respectively. Compositions and morphologies of the SAMs before and after immobilization of Cyt c were characterized by X-ray photoelectron spectroscopy, Raman spectroscopy, scanning electron microscopy, and atomic force microscopy.
Genome sequence and analysis of a broad-host range lytic bacteriophage that infects the Bacillus cereus group
Authors: El-Arabi Tarek F , Griffiths Mansel W , She Yi-Min , Villegas Andre , Lingohr Erika J , Kropinski Andrew M
Published: February 2013

Background

Comparatively little information is available on members of the Myoviridae infecting low G+C content, Gram-positive host bacteria of the family Firmicutes. While numerous Bacillus phages have been isolated up till now only very few Bacillus cereus phages have been characterized in detail.

Results

Here we present data on the large, virulent, broad-host-range B. cereus phage vB_BceM_Bc431v3 (Bc431v3). Bc431v3 features a 158,618 bp dsDNA genome, encompassing 239 putative open reading frames (ORFs) and, 20 tRNA genes encoding 17 different amino acids. Since pulsed-field gel electrophoresis indicated that the genome of this phage has a mass of 155-158 kb Bc431v3 DNA appears not to contain long terminal repeats that are found in the genome of Bacillus phage SPO1.

Conclusions

Bc431v3 displays significant sequence similarity, at the protein level, to B. cereus phage BCP78, Listeria phage A511 and Enterococcus phage ØEF24C and other morphologically related phages infecting Firmicutes such as Staphylococcus phage K and Lactobacillus phage LP65. Based on these data we suggest that Bc431v3 should be included as a member of the Spounavirinae; however, because of all the diverse taxonomical information has been addressed recently, it is difficult to determine the genus. The Bc431v3 phage contains some highly unusual genes such as gp143 encoding putative tRNAHis guanylyltransferase. In addition, it carries some genes that appear to be related to the host sporulation regulators. These are: gp098, which encodes a putative segregation protein related to FstK/SpoIIIE DNA transporters; gp105, a putative segregation protein; gp108, RNA polymerase sigma factor F/B; and, gp109 encoding RNA polymerase sigma factor G.
Potential of silver against human colon cancer: (synthesis, characterization and crystal structures of xylyl (Ortho, meta, & Para) linked bis-benzimidazolium salts and Ag(I)-NHC complexes: In vitroanticancer studies)
Authors: Iqbal Muhammad Adnan , Haque Rosenani A , Nasri Siti Fatimah , Majid AMS Abdul , Ahamed Mohamed B Khadeer , Farsi Elham , Fatima Tabinda
Published: February 2013

Background

Since the first successful synthesis of Ag(I)-N-heterocyclic carbene complex in 1993, this class of compounds has been extensively used for transmetallation reactions where the direct synthesis using other metal ions was either difficult or impossible. Initially, silver(I)-NHC complexes were tested for their catalytic potential but could not get fame because of lower potential compare to other competent compounds in this field; however, these compounds proved to have vital antimicrobial activities. These encouraging biomedical applications further convinced researchers to test these compounds against cancer. The current work has been carried out with this aim.

Results

N-ipropylbenzimidazole was synthesized by reaction of benzimidazole with
i
propyl bromide. The subsequent treatment of the resulting N-alkylbenzimidazole with ortho/meta/para-(bromomethylene) benzene afforded corresponding bis-benzimidazolium bromides (5-7). The counter anion (Br-) of each salt was replaced by hexaflourophosphate (PF6
-) for the ease of handling and further purification (8-10). Each salt (Ligand), in halide form, was further allowed to react with Ag2O with stirring at room temperature for a period of two days to synthesize dinuclear Ag(I)-NHC complexes (11-13). All synthesized compounds were characterized by spectroscopic techniques and microanalysis. Molecular structures of compounds 5, 9 & 10 were established through single crystal x-ray diffraction technique. All the compounds were assessed for their anti-proliferation test on human colorectal cancer cell line (HCT 116). Results showed that the ligands (5-10) showed mild to negligible cytotoxicity on HCT 116 cells whereas respective silver complexes (11-13) exhibited dose dependent cytotoxicity towards the colon cancer cells with IC50 ranges between 9.7 to 44.5 μM. Interestingly, the complex 13 having para-xylyl spacer was found the most active (IC50 9.7 μM) that verifies our previously reported results.

Conclusions

All the bis-benzimidazolium salts (8-10) were found inactive whereas after bonding with silver cations, the Ag(I)-NHC complexes (11-13) showed a dose dependent cytotoxic activity. This proved that silver practice an important role in death of cancer cells. Also, the N-alkyl/aryl substitutions and ortho/metal/para xylyl units regulate the cytotoxicity.
Organotypic brain slices: a model to study the neurovascular unit micro-environment in epilepsies
Authors: Morin-Brureau Mélanie , De Bock Frédéric , Lerner-Natoli Mireille
Published: February 2013

Background

It is now recognized that the neuro-vascular unit (NVU) plays a key role in several neurological diseases including epilepsy, stroke, Alzheimer’s disease, multiple sclerosis and the development of gliomas. Most of these disorders are associated with NVU dysfunction, due to overexpression of inflammatory factors such as vascular endothelial growth factor (VEGF). Variousin vitromodels have been developed previously to study the micro-environment of the blood–brain barrier (BBB). However none of thesein vitromodels contained a complete complement of NVU cells, nor maintained their interactions, thus minimizing the influence of the surrounding tissue on the BBB development and function. The organotypic hippocampal culture (OHC) is an integrativein vitromodel that allows repeated manipulations over time to further understand the development of cell circuits or the mechanisms of brain diseases.

Methods/design

OHCs were cultured from hippocampi of 6–7 day-old Sprague Dawley rats. After 2 weeks in culture, seizures were induced by application of kainate or bicuculline into culture medium. The regulation of BBB integrity under physiological and pathological conditions was evaluated by immunostaining of the main tight junction (TJ) proteins and of the basal membrane of microvessels. To mimic or prevent BBB disassembly, we used diverse pro- or anti-angiogenic treatments.

Discussion

This study demonstrates that NVU regulation can be investigated using OHCs. We observed in this model system an increase in vascularization and a down-regulation of TJ proteins, similar to the vascular changes described in a chronic focus of epileptic patients, and in rodent models of epilepsy or inflammation. We observed that Zonula occludens-1 (ZO-1) protein disappeared after seizures associated with neuronal damage. In these conditions, the angiopoeitin-1 system was down-regulated, and the application of r-angiopoeitin-1 allowed TJ re-assembly. This article demonstrates that organotypic culture is a useful model to decipher the links between epileptic activity and vascular damage, and also to investigate NVU regulation in diverse neurological disorders.
High proportion of healthcare-associated urinary tract infection in the absence of prior exposure to urinary catheter: a cross-sectional study
Authors: Uçkay Ilker , Sax Hugo , Gayet-Ageron Angèle , Ruef Christian , Mühlemann Kathrin , Troillet Nicolas , Petignat Christiane , Bernasconi Enos , Balmelli Carlo , Widmer Andreas , Boubaker Karim , Pittet Didier ,   for the Swiss-NOSO network
Published: February 2013

Background

Exposure to urinary catheters is considered the most important risk factor for healthcare-associated urinary tract infection (UTI) and is associated with significant morbidity and substantial extra-costs. In this study, we assessed the impact of urinary catheterisation (UC) on symptomatic healthcare-associated UTI among hospitalized patients.

Methods

A nationwide period prevalence survey of healthcare-associated infections was conducted during 1 May to 30 June 2004 in 49 Swiss hospitals and included 8169 adult patients (4313 female; 52.8%) hospitalised in medical, surgical, intermediate, and intensive care wards. Additional data were collected on exposure to UC to investigate factors associated with UTI among hospitalised adult patients exposed and non-exposed to UC.

Results

1917 (23.5%) patients were exposed to UC within the week prior to survey day; 126 (126/8169; 1.5%) developed UTI. Exposure to UC preceded UTI only in 73 cases (58%). By multivariate logistic regression analysis, UTI was independently associated with exposure to UC (odds ratio [OR], 3.9 [95% CI, 2.6-5.9]), female gender (OR, 2.1 [95% CI, 1.4-3.1]), an American Society of Anesthesiologists’ score > 2 points (OR, 3.2 [95% CI, 1.1-9.4], and prolonged hospital stay >20 days (OR, 1.9 [95% CI, 1.4-3.2]. Further analysis showed that the only significant factor for UTI with exposure to UC use was prolonged hospital stay >40 days (OR, 2.9 [95% CI, 1.3-6.1], while female gender only showed a tendency (OR, 1.6 [95% CI, 1.0-2.7]. In the absence of exposure to UC, the only significant risk factor for UTI was female gender (OR, 3.3 [95% CI, 1.7-6.5]).

Conclusions

Exposure to UC was the most important risk factor for symptomatic healthcare-associated UTI, but only concerned about half of all patients with UTI. Further investigation is warranted to improve overall infection control strategies for UTI.
VDR hypermethylation and HIV-induced T cell loss
Authors: Chandel Nirupama , Husain Mohammad , Goel Hersh , Salhan Divya , Lan Xiqian , Malhotra Ashwani , McGowan Joseph , Singhal Pravin C
Published: February 2013

HIV-induced T cell loss was mediated through ROS generation in response to HIV-induced VDR methylation and associated activation of the RAS.

Epigenetics contributes to the development of variety of diseases by modulation of gene expression. We evaluated the effect of HIV-induced VDR methylation on loss of TCs. HIV/TC displayed enhanced VDR-CpG methylation and increased expression of Dnmt3b but attenuated expression of VDR. A demethylating agent, AZA, inhibited this effect of HIV. HIV/TC also displayed the activation of the RAS, which was reversed by EB (a VDA). Further, HIV/TCs displayed enhanced generation of ROS and induction of DSBs but attenuated DNA repair response. However, in the presence of AZA, EB, LOS (a RAS blocker), Cat, and tempol (free radical scavengers), HIV-induced TC ROS generation and induction of DSBs were attenuated but associated with enhanced DNA repair. Additionally, AZA, EB, and LOS provided protection against HIV-induced TC apoptosis. These findings suggested that HIV-induced TC apoptosis was mediated through ROS generation in response to HIV-induced VDR methylation and associated activation of the RAS.
The Prenyl Group Contributes to Activities of Phytoestrogen 8-Prenynaringenin in Enhancing Bone Formation and Inhibiting Bone Resorption In Vitro
Authors: Ming Lei-Guo , Lv Xiang , Ma Xiao-Ni , Ge Bao-Feng , Zhen Ping , Song Peng , Zhou Jian , Ma Hui-Ping , Xian Cory J , Chen Ke-Ming
Published: February 2013

Previous studies have found that 8-prenylflavonoids have a higher osteogenic activity than do flavonoids, which suggested that the 8-prenyl group may play an active role in bone-protective properties. To address this hypothesis, activities of 8-prenylnaringenin (PNG) and naringenin (NG) in osteoblast and osteoclast differentiation and function were compared in vitro. PNG was found to have a stronger ability than NG to improve osteoblast differentiation and osteogenic function in cultured rat calvarial osteoblasts, as demonstrated by levels of alkaline phosphatase activity, osteocalcin, calcium deposition, and the number and area of mineralized bone nodules, as well as mRNA expression of osteogenesis-related genes Bmp-2, OSX, and Runx-2. In addition, although expression of osteoclastogenic inducer receptor activator of nuclear factor kappa-B ligand (RANKL) was not affected, that of osteoclastogenesis inhibitor osteoprotegerin (OPG) and consequently the OPG/RANKL ratio were increased, more potently by PNG than NG. PNG was also found to have a higher potency than NG in inhibiting the osteoclast formation in rabbit bone marrow cells and their resorptive activity, as revealed by lower numbers of osteoclasts formed, lower numbers and areas of bone resorption pits, and lower mRNA expression levels of tartrate-resistant acid phosphatase and cathepsin K. Furthermore, PNG induced apoptosis of mature osteoclasts at a higher degree and at an earlier time than did NG. These results indicate that the 8-prenyl group plays an important role and contributes to the higher bone-protective activity of PNG in comparison with NG.
Novel Higher-Order Epigenetic Regulation of theBdnfGene upon Seizures
Authors: Walczak Agnieszka , Szczepankiewicz Andrzej A. , Ruszczycki Blazej , Magalska Adriana , Zamlynska Katarzyna , Dzwonek Joanna , Wilczek Ewa , Zybura-Broda Katarzyna , Rylski Marcin , Malinowska Monika , Dabrowski Michal , Szczepinska Teresa , Pawlowski Krzysztof , Pyskaty Marta , Wlodarczyk Jakub , Szczerbal Izabela , Switonski Marek , Cremer Marion , Wilczynski Grzegorz M.
Published: February 2013

Studies in cultured cells have demonstrated the existence of higher-order epigenetic mechanisms, determining the relationship between expression of the gene and its position within the cell nucleus. It is unknown, whether such mechanisms operate in postmitotic, highly differentiated cell types, such as neuronsin vivo. Accordingly, we examined whether the intranuclear positions ofBdnfandTrkbgenes, encoding the major neurotrophin and its receptor respectively, change as a result of neuronal activity, and what functional consequences such movements may have. In a rat model of massive neuronal activation upon kainate-induced seizures we found that elevated neuronal expression ofBdnfis associated with its detachment from the nuclear lamina, and translocation toward the nucleus center. In contrast, the position of stably expressedTrkbremains unchanged after seizures. Our study demonstrates that activation-dependent architectural remodeling of the neuronal cell nucleusin vivocontributes to activity-dependent changes in gene expression in the brain.
Rheb Activation in Subventricular Zone Progenitors Leads to Heterotopia, Ectopic Neuronal Differentiation, and Rapamycin-Sensitive Olfactory Micronodules and Dendrite Hypertrophy of Newborn Neurons
Authors: Lafourcade Carlos A. , Lin Tiffany V. , Feliciano David M. , Zhang Longbo , Hsieh Lawrence S. , Bordey Angélique
Published: February 2013

Mammalian target of rapamycin (mTOR) hyperactivity in perinatal neural progenitor cells (NPCs) of tuberous sclerosis complex 1 (Tsc1) heterozygote mice leads to heterotopia and abnormal neuronal morphogenesis as seen in patients with tuberous sclerosis. Considering that pathological hyperactive mTOR also occurs in individuals carrying no genetic mutations, we examined whether increasing mTOR activity in neonatal NPCs of wild-type mice would recapitulate the above phenotypes. Electroporation of a plasmid encoding constitutively active Ras-homolog enriched in brain (RhebCA) into subventricular zone NPCs increased mTOR activity in newborn cells. At 19 d post-electroporation (dpe), heterotopia and ectopic cells with a neuronal morphology were observed along the migratory path [rostral migratory stream (RMS)] and in the olfactory bulb (OB). These ectopic cells displayed action potentials and received synaptic inputs identifying them as synaptically integrated neurons. RMS heterotopias contained astrocytes, neurons, and entrapped neuroblasts. Immunostaining at 3 dpe revealed the presence of Mash1+Olig2−cells in the migratory route accompanied by ectopic neuronal differentiation and altered direction and speed of neuroblast migration at 7 dpe, suggesting a non-cell-autonomous disruption of migration. At >19 dpe, newborn RhebCA-expressing neurons displayed altered distribution and formed micronodules in the OB. In addition, they displayed increased dendritic complexity along with altered membrane biophysics and increased frequency of GABAergic synaptic inputs. OB heterotopia, micronodules, and dendrite hypertrophy were notably prevented by rapamycin treatment, suggesting their mTOR dependence. Collectively, these data show that increasing mTOR activity in neonatal NPCs of wild-type mice recapitulate the pathologies observed inTsc1mutant mice. In addition, increased mTOR activity in individuals without known mutations could significantly impact neurogenesis and circuit formation.
A-Kinase Anchoring Protein–Calcineurin Signaling in Long-Term Depression of GABAergic Synapses
Authors: Dacher Matthieu , Gouty Shawn , Dash Steven , Cox Brian M. , Nugent Fereshteh S.
Published: February 2013

The postsynaptic scaffolding A-kinase anchoring protein 79/150 (AKAP79/150) signaling complex regulates excitatory synaptic transmission and strength through tethering protein kinase A (PKA), PKC, and calcineurin (CaN) to the postsynaptic densities of neurons (Sanderson and Dell'Acqua, 2011), but its role in inhibitory synaptic transmission and plasticity is unknown. Using immunofluorescence and whole-cell patch-clamp recording in rat midbrain slices, we show that activation of postsynaptic D2-like family of dopamine (DA) receptor in the ventral tegmental area (VTA) induces long-term depression (LTD) of GABAergic synapses on DA neurons through an inositol triphosphate receptor-mediated local rise in postsynaptic Ca2+and CaN activation accompanied by PKA inhibition, which requires AKAP150 as a bridging signaling molecule. Our data also illuminate a requirement for a clathrin-mediated internalization of GABAAreceptors in expression of LTDGABA. Moreover, disruption of AKAP–PKA anchoring does not affect glutamatergic synapses onto DA neurons, suggesting that the PKA–AKAP–CaN complex is uniquely situated at GABAAreceptor synapses in VTA DA neurons to regulate plasticity associated with GABAAreceptors. Drug-induced modulation of GABAergic plasticity in the VTA through such novel signaling mechanisms has the potential to persistently alter the output of individual DA neurons and of the VTA, which may contribute to the reinforcing or addictive properties of drugs of abuse.
Mapping the Subcellular Distribution of α-Synuclein in Neurons using Genetically Encoded Probes for Correlated Light and Electron Microscopy: Implications for Parkinson's Disease Pathogenesis
Authors: Boassa Daniela , Berlanga Monica L. , Yang Mary Ann , Terada Masako , Hu Junru , Bushong Eric A. , Hwang Minju , Masliah Eliezer , George Julia M. , Ellisman Mark H.
Published: February 2013

Modifications to the gene encoding human α-synuclein have been linked to the development of Parkinson's disease. The highly conserved structure of α-synuclein suggests a functional interaction with membranes, and several lines of evidence point to a role in vesicle-related processes within nerve terminals. Using recombinant fusions of human α-synuclein, including new genetic tags developed for correlated light microscopy and electron microscopy (the tetracysteine-biarsenical labeling system or the new fluorescent protein for electron microscopy, MiniSOG), we determined the distribution of α-synuclein when overexpressed in primary neurons at supramolecular and cellular scales in three dimensions (3D). We observed specific association of α-synuclein with a large and otherwise poorly characterized membranous organelle system of the presynaptic terminal, as well as with smaller vesicular structures within these boutons. Furthermore, α-synuclein was localized to multiple elements of the protein degradation pathway, including multivesicular bodies in the axons and lysosomes within neuronal cell bodies. Examination of synapses in brains of transgenic mice overexpressing human α-synuclein revealed alterations of the presynaptic endomembrane systems similar to our findings in cell culture. Three-dimensional electron tomographic analysis of enlarged presynaptic terminals in several brain areas revealed that these terminals were filled with membrane-bounded organelles, including tubulovesicular structures similar to what we observedin vitro. We propose that α-synuclein overexpression is associated with hypertrophy of membrane systems of the presynaptic terminal previously shown to have a role in vesicle recycling. Our data support the conclusion that α-synuclein is involved in processes associated with the sorting, channeling, packaging, and transport of synaptic material destined for degradation.
NF-κB Forms a Complex with the Chromatin Remodeler BRG1 to Regulate Schwann Cell Differentiation
Authors: Limpert Allison S. , Bai Shujun , Narayan Malathi , Wu Jiang , Yoon Sung Ok , Carter Bruce D. , Lu Q. Richard
Published: February 2013

In the developing peripheral nervous system, axon-derived signals stimulate Schwann cells to undergo a global genetic reprogramming involving the cessation of cellular division and the upregulation of myelin genes. How such a comprehensive change in gene transcription is regulated is poorly understood. Here we report that BRG1/SMARCA4, the central helicase of the mammalian SWI/SNF-related chromatin remodeling complex, is required for Schwann cells to differentiate and form myelin, bothin vitroandin vivo, in the mouse. BRG1 was highly activated in Schwann cells at early stages of myelination, and loss of the enzyme inhibited their differentiation and completely prevented myelin formation. Furthermore, we identify NF-κB as a key transcription factor that associates with the BRG1 complex in response to neuregulin 1 type III. During myelination, BRG1 was activated through the formation of a complex with NF-κB, and both proteins bound to the promoter region of Sox10, an inducer of myelination. These findings delineate a novel mechanism whereby axonal signals promote myelination through the remodeling of chromatin structure.
Auditory–Motor Interactions for the Production of Native and Non-Native Speech
Authors: Parker Jones 'Ōiwi , Seghier Mohamed L. , Kawabata Duncan Keith J. , Leff Alex P. , Green David W. , Price Cathy J.
Published: February 2013

During speech production, auditory processing of self-generated speech is used to adjust subsequent articulations. The current study investigated how the proposed auditory–motor interactions are manifest at the neural level in native and non-native speakers of English who were overtly naming pictures of objects and reading their written names. Data were acquired with functional magnetic resonance imaging and analyzed with dynamic causal modeling. We found that (1) higher activity in articulatory regions caused activity in auditory regions to decrease (i.e., auditory suppression), and (2) higher activity in auditory regions caused activity in articulatory regions to increase (i.e., auditory feedback). In addition, we were able to demonstrate that (3) speaking in a non-native language involves more auditory feedback and less auditory suppression than speaking in a native language. The difference between native and non-native speakers was further supported by finding that, within non-native speakers, there was less auditory feedback for those with better verbal fluency. Consequently, the networks of more fluent non-native speakers looked more like those of native speakers. Together, these findings provide a foundation on which to explore auditory–motor interactions during speech production in other human populations, particularly those with speech difficulties.
Persistent Receptor Activity Underlies Group I mGluR-Mediated Cellular Plasticity in CA3 Neuron
Authors: Young Steven R. , Chuang Shih-Chieh , Zhao Wangfa , Wong Robert K. S. , Bianchi Riccardo
Published: February 2013

Plastic changes in cortical activities induced by group I metabotropic glutamate receptor (mGluR) stimulation include epileptogenesis, expressedin vitroas the conversion of normal neuronal activity to persistent, prolonged synchronized (ictal) discharges. At present, the mechanism that maintains group I mGluR-induced plasticity is not known. We examined this issue using hippocampal slices from guinea pigs and mice. Agonist [(S)-3,5-dihydroxyphenylglycine (DHPG), 30–50 μm)] stimulation of group I mGluRs induces persistent prolonged synchronized (ictal-like) discharges in CA3 that are associated with three identified excitatory cellular responses—suppression of spike afterhyperpolarizations, activation of a voltage-dependent cationic current, and increase in neuronal input resistance. Persistent prolonged synchronized discharges and the underlying excitatory cellular responses maintained following induction were reversibly blocked by mGluR1 antagonists [(S)-+-α-amino-4-carboxy-2-methylbenzeneacetic acid (LY 367385), 50, 100 μm; CPCCOEt (hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester, 100 μm], and to a lesser extent by the mGluR5 antagonist MPEP [2-methyl-6-(phenylethynyl)pyridine hydrochloride, 50 μm]. Activation of persistent cellular responses to DHPG were unaffected by tetrodotoxin (0.5–1 μm) or perfusion with low Ca2+(0.2 mm)–Mn2+(0.5 mm) media—conditions that suppress endogenous glutamate release. The pharmacological profile of the blocking action of the group I mGluR antagonist MCPG [(RS)-α-methyl-4-carboxyphenylglycine, 50–500 μm] on persistent cellular responses was different from that on cellular responses directly activated by DHPG. These data indicate that transient stimulation of group I mGluRs alters receptor properties, rendering them persistently active in the absence of applied agonist or endogenous glutamate activation. Persistent receptor activities, primarily involving mGluR1, maintain excitatory cellular responses and emergent prolonged synchronized discharges.