bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional Differences in Smoking, Drinking, and Physical Activities of Chinese Residents
Authors: Li Rongjie , Wang Debin , Chen Jing , Chai Jing , Tang Mengsha
Published: February 2012

Aims. This article aims at analyzing regional differences in smoking, drinking, and physical activities in China and informing cross-regional initiatives addressing these behaviors. Methods. Data were extracted from available large-scale surveys. Index of dissimilarity (ID), linear correlation, and geographical mapping were used to analyze regional differences in the prevalence of smoking (PS), smoking cessation (PSC), regular drinking (PRD), and physical activities (PPA). Results. Significant differences existed across regions in all the behaviors ( P < .01). IDs ranged from 0.04 to 0.42. IDs of PRD and PPA were much higher than IDs of PS and PSC. Linear correlation coefficients of the 4 indicators by regions varied substantially ranging (in absolute value) from 0.031 to 0.982. Characteristic formats of geographical distribution were found with PS, PSC, and PRD and PPA being in “high plateau,” “low plateau,” and “shifting” patterns, respectively. Conclusions. Distinct regional disparities in health behavior exist, and socioculturally and contextually competitive policies and interventions are needed.
Magnetorheological valve in servo applications
Authors: Kostamo Esa , Kostamo Jari , Kajaste Jyrki , Pietola Matti
Published: February 2012

In this article, the servo property of a high-performance magnetorheological valve will be evaluated by closing the pressure feedback loop. The magnetorheological valve developed in this study has two separately controllable fluid flow channels and is especially designed for high-frequency applications. A state space model of the magnetorheological valve from the control signal to the pressure output will be identified, and the identified model is used for tuning a proportional–integral–derivative controller and for simulation of the closed-loop system. Finally, the controller will be implemented to a control computer, and the pressure output will be controlled in a real-time control loop. By analyzing the dynamic and static performance of the magnetorheological servo valve, it can be stated that the magnetorheological valve has a good potential for high-frequency pressure and force control applications.
Organizing for the Green Economy
Authors: Charnovitz Steve
Published: February 2012

This essay discusses some current proposals for improving global environmental governance and suggests that the debate be shifted to the emerging paradigm of how to organize to achieve a green economy
Technology Is Not Enough
Authors: Mitchell Ronald B.
Published: February 2012

Reducing human emissions of carbon dioxide by 80% by 2100 requires more than technological innovation. Historical rates of emissions decline due to such innovation of about 0.7% are insufficient to offset the 3% growth in emissions that stems from population and per capita income growth. Existing scientific and political debates are dominated by a “technophilic optimism” that projects emission reductions from technological improvement that are not supported by the evidence. If we fail to develop policies proactively to constrain population, affluence, and consumption while respecting other human values, we will almost certainly face impacts from climate change that constrain population, affluence, and consumption for us.
On the existence of Eshelby’s equivalent ellipsoidal inclusion solution
Authors: Kuykendall William P , Cash William D , Barnett David M , Cai Wei
Published: February 2012

The existence of Eshelby’s equivalent inclusion solution is proved for a non-degenerate ‘transformed’ ellipsoidal inhomogeneity in an infinite anisotropic linear elastic matrix. We prove the invertibility of the fourth rank tensor expression, [Formula: see text], where C is the stiffness tensor of the matrix, C′ is the stiffness tensor of the inhomogeneity, I is the Eshelby tensor, and [Formula: see text] is the symmetric identity tensor. Taking advantage of the positive definiteness of certain tensor expressions, a proof-by-contradiction using energy arguments is posited that eliminates the possibility that the above expression is singular. Because the tensor expression is non-singular, it can always be inverted and Eshelby’s equivalent ellipsoidal inclusion method can be used to find the stress and strain fields in both the matrix and inhomogeneity.
Anesthetic Considerations During Minimally Invasive Mitral Valve Surgery
Authors: Vernick William J. , Woo Joseph Y.
Published: February 2012

Advances in instruments and visualization tools as well as circulatory systems for cardiopulmonary bypass during the late 1990s have stimulated widespread adoption of minimally invasive mitral valve surgery (MIMVS). Today, MIMVS is the standard approach for many surgeons and institutions. There are multiple benefits of MIMVS. Patient satisfaction and improved cosmesis are important. Additionally, studies have consistently shown faster recovery times and less associated pain with MIMVS. Statistically significant improvement in bleeding, transfusion, incidence of atrial fibrillation, and time to resumption of normal activities with MIMVS has also been shown when comparing MIMVS with conventional mitral surgery. Most important, these benefits have been achieved without sacrificing perioperative safety or durability of surgical repair. Although a steep learning curve still exists given the high level of case complexity, continued development fueled by increasing patient demand may allow for even further expansion in the use of minimal invasive techniques.
Ordering, Enrolling, and Dismissing
Authors: White Paul , Hillman Alexandra , Latimer Joanna
Published: February 2012

Drawing on ethnographies of three areas of hospital life in the United Kingdom, this article explores the different logics played out through moments of access to hospital services. The authors make explicit the character of the hospital as heterotopia where different social actors are required to “fit” in with the organizational requirements of the hospital. What becomes clear is how the hospital as institution can accommodate particular logics at particular times that are incommensurate with the organization of the hospital and the “care” of patients. Such accommodation makes explicit the contestable characteristics of the hospital where alignments are made between multiple logics. Through processes of ordering, enrolling, or even dismissing potential patients (or even logics), the authors argue that divisions are labored across hospital life and are worked to accomplish particular social worlds. The issue of which social worlds are being labored and how they work for or against a logic of care is made explicit here. Through their ethnographic work, the authors show how through processes of ordering, enrolling, and dismissing persons, subject positions, and logics during moments of access, the hospital can be understood as a complex heterotopia that works politics through clinical and managerial practice.
Have the cake and eat it
Authors: Lindberg Staffan I
Published: February 2012

A vast literature suggests that voters in new democracies ‘sell’ their vote to patrons providing private or small-scale club goods, or, alternatively, that such goods are distributed along ethnic lines to reinforce ethnic voting. In either case the outcome is undermining democratic accountability. This study finds that citizens in one new democracy – Ghana – expect (and get) the patronage but at the same time engage in economic voting. Eighty-five percent of citizens first and foremost expect their legislators to supply private or small-scale ‘club’ goods. This acts as a strong incentive for politicians to actually supply such goods, which is confirmed by participants’ observational data and more than 250 interviews conducted by the author. Despite this, citizens do not vote based on how well or how poorly incumbent MPs provide clientelistic goods. A multivariate analysis reveals that voting for the opposition or the incumbent is determined by evaluations of the state of the national economy and of the government’s policies. What the literature has portrayed as an ‘either-or’ is ‘both’, and this is perfectly rational: Extract as much as one can in terms of private and small club goods but vote based on economic factors. The literature suggests that clientelism dominates elections in newer democracies and thus undermines democracy. The findings from this study suggest that while distribution of clientelistic goods is common, this does not necessarily undermine the mechanism of democratic accountability in elections.
Explaining MPs’ perceptions of voters’ positions in a party-mediated representation system
Authors: Belchior Ana Maria
Published: February 2012

The article addresses the crucial but still relatively understudied issue of political perceptions, specifically the perceptions of members of parliament (MPs) regarding the positioning of voters on the left–right spectrum, and the accuracy thereof. It focuses on the Portuguese case, which differs from others studied to date in terms of the links between MPs and voters (in contrast to prior research, Portuguese voters do not vote for an MP candidate but for a party list; the representation process is mediated by political parties). The article begins by characterizing Portuguese MP perceptions of voters’ left–right positions, and then explores the reasons for MPs’ perceptual accuracy. The findings show that MP perceptions are shaped by wishful thinking, reiterating previous research, and that party integration is an important new factor explaining perceptual accuracy.
A Perfusion fMRI Study of the Neural Correlates of Sustained-Attention and Working-Memory Deficits in Chronic Traumatic Brain Injury
Authors: Kim Junghoon , Whyte John , Patel Sunil , Europa Eduardo , Slattery John , Coslett H. Branch , Detre John A.
Published: February 2012

Background. Given that traumatic brain injury (TBI) results in chronic alteration of baseline cerebral perfusion, a perfusion functional MRI (fMRI) method that dissociates resting- and task-related cerebral blood flow (CBF) changes can be useful in noninvasively investigating the neural correlates of cognitive dysfunction and recovery in TBI. Objective. The authors used continuous arterial spin-labeled (ASL) perfusion fMRI to characterize CBF at rest and during sustained-attention and working-memory tasks. Methods. A total of 18 to 21 individuals with moderate to severe TBI and 14 to 18 demographically matched healthy controls completed 3 continuous 6-minute perfusion fMRI scans (resting, visual sustained attention, and 2-back working memory). Results. For both tasks, TBI participants showed worse behavioral performance than controls. Voxelwise neuroimaging analysis of the 2-back task found that group differences in task-induced CBF changes were localized to bilateral superior occipital cortices and the left superior temporal cortex. Whereas controls deactivated these areas during task performance, TBI participants tended to activate these same areas. These regions were among those found to be disproportionately hypoperfused at rest after TBI. For both tasks, the control and TBI groups showed different patterns of correlation between performance and task-related CBF changes. Conclusions. ASL perfusion fMRI demonstrated differences between individuals with TBI and healthy controls in resting perfusion and in task-evoked CBF changes as well as different patterns of performance-activation correlation. These results are consistent with the notion that sensory/attentional modulation deficits contribute to higher cognitive dysfunction in TBI.
‘The industry’s the new road’: Crime, commodification and street cultural tropes in UK urban music
Authors: Ilan Jonathan
Published: February 2012

With original authors and audiences from the most disadvantaged and excluded communities across Western society, urban music has been equally scorned and sought out for its referencing of, and/or association with, criminal activity. Urban music (such as rap from the United States) can be understood as generating both ‘respectable fears’ and ‘subcultural capital’, appealing to youthful consumers who are seduced by its ostensibly transgressive character. This appeal is linked to the urban communities which incubated and popularised both the music and the ‘street culture’ of its underprivileged population. The wisdom has followed that the more ‘ghetto’ the music, the greater its ability to court controversy and generate record sales. Interestingly, the latest generation of UK urban artistes has bucked this trend, eschewing violent imagery and metaphor, courting a ‘mainstream’ aesthetic and actively referencing ‘respectable’ routes to inclusion such as engaging with education and running small businesses. This paper reflects on British ‘grime’ music, demonstrating that new media and music industry democratisation can alter the manner by which crime and street culture are commodified. It argues that where there is a perception of threat connected to street-level urban music authored by those with supposed links to criminality, the lines between real crime and its mediated representation can become blurred. The authorities and the music industry may respond by effectively criminalising and excluding an entire genre. In the case of UK urban music, artistes have adopted a strategy to succeed within the mainstream industry which, as opposed to US rappers, involves muting their links to street culture.
Grip strength characteristics using force–time curves in rheumatoid hands
Authors: Dias J. J. , Singh H. P. , Taub Nick , Thompson J.
Published: February 2012

The use of force–time curves in rheumatoid hands was investigated to assess peak force, average force, total grip time, area under the curve, and variability of the plateau region of the curves to identify the impact of different rheumatoid hand deformities on grip strength. We studied 43 patients — 10 men and 33 women — with established rheumatoid arthritis affecting their hands. Mean age was 61 years and mean duration of hand involvement was 13 years. Of the 86 hands, 38 had no finger deformity, eight had metacarpophalangeal joint ulnar deviation without any additional finger deformities, 16 had swan neck deformities, and 10 had boutonnière deformities. Fourteen hands had a combination of deformities. The hands with combined deformities were the weakest, had poor grip strength (34.7 N, SE 8), and were able to sustain grip for only a short time (22 sec, SE 3). Swan neck deformity also profoundly affects the magnitude (49.8 N, SE 7) and sustainability of grip (15 sec, SE 2). Even when only one finger had a swan neck deformity the mean strength was poor at 45 N. Swan neck deformity causes greater loss of strength than boutonnière deformity (82.7 N, SE 15). The strongest rheumatoid hands were those with only ulnar deviation deformities (90.8 N, SE 14). The area under the curve best predicted disability assessed using the Patient Evaluation Measure.
Fruit and Vegetable Consumption and Body Mass Index
Authors: Azagba Sunday , Sharaf Mesbah Fathy
Published: February 2012

Background: Empirical evidence on the relationship between consumption of fruits and vegetables and body weight is inconclusive. Previous studies mostly use linear regression methods to study the correlates of the conditional mean of body mass index (BMI). This approach may be less informative if the association between fruit and vegetable consumption and BMI significantly varies across the BMI distribution. Objective: The association between fruit and vegetable consumption and the BMI is examined using quantile regression. Methods: A nationally representative sample of 11,818 individuals from the Canadian Community Health Survey (2004) is used. A quantile regression model is estimated to account for the potential heterogeneous association between fruit and vegetable intake and BMI at different points of the conditional BMI distribution. The analyses are stratified by gender. Results: The multivariate analyses reveal that the association between fruit and vegetable intake and BMI is negative and statistically significant for both males and females; however, this association varies across the conditional quantiles of the BMI distribution. In particular, the estimates are larger for individuals at the higher quantiles of the distribution. The ordinary least squares (OLS) model overstates (understates) the association between FV intake and BMI at the lower (higher) half of the conditional BMI distribution. Conclusion: Findings of the standard models that assume uniform response across different quantiles of BMI distribution may be misleading. The findings of this paper suggest that increasing the intake of fruits and vegetables may be an effective dietary strategy to control weight and mitigate the risk of obesity.
ParentChecker: a computer program for automated inference of missing parental genotype calls and linkage phase correction
Authors: Hu Zhiqiu , Ehlers Jeffrey D , Roberts Philip A , Close Timothy J , Lucas Mitchell R , Wanamaker Steve , Xu Shizhong
Published: February 2012

Background

Accurate genetic maps are the cornerstones of genetic discovery, but their construction can be hampered by missing parental genotype information. Inference of parental haplotypes and correction of phase errors can be done manually on a one by one basis with the aide of current software tools, but this is tedious and time consuming for the high marker density datasets currently being generated for many crop species. Tools that help automate the process of inferring parental genotypes can greatly speed the process of map building. We developed a software tool that infers and outputs missing parental genotype information based on observed patterns of segregation in mapping populations. When phases are correctly inferred, they can be fed back to the mapping software to quickly improve marker order and placement on genetic maps.

Results

ParentChecker is a user-friendly tool that uses the segregation patterns of progeny to infer missing genotype information of parental lines that have been used to construct a mapping population. It can also be used to automate correction of linkage phase errors in genotypic data that are in ABH format.

Conclusion

ParentChecker efficiently improves genetic mapping datasets for cases where parental information is incomplete by automating the process of inferring missing genotypes of inbred mapping populations and can also be used to correct linkage phase errors in ABH formatted datasets.
Linking public health agencies and hospitals for improved emergency preparedness: North Carolina's public health epidemiologist program
Authors: Markiewicz Milissa , Bevc Christine A , Hegle Jennifer , Horney Jennifer A , Davies Megan , MacDonald Pia DM
Published: February 2012

Background

In 2003, 11 public health epidemiologists were placed in North Carolina's largest hospitals to enhance communication between public health agencies and healthcare systems for improved emergency preparedness. We describe the specific services public health epidemiologists provide to local health departments, the North Carolina Division of Public Health, and the hospitals in which they are based, and assess the value of these services to stakeholders.

Methods

We surveyed and/or interviewed public health epidemiologists, communicable disease nurses based at local health departments, North Carolina Division of Public Health staff, and public health epidemiologists' hospital supervisors to 1) elicit the services provided by public health epidemiologists in daily practice and during emergencies and 2) examine the value of these services. Interviews were transcribed and imported into ATLAS.ti for coding and analysis. Descriptive analyses were performed on quantitative survey data.

Results

Public health epidemiologists conduct syndromic surveillance of community-acquired infections and potential bioterrorism events, assist local health departments and the North Carolina Division of Public Health with public health investigations, educate clinicians on diseases of public health importance, and enhance communication between hospitals and public health agencies. Stakeholders place on a high value on the unique services provided by public health epidemiologists.

Conclusions

Public health epidemiologists effectively link public health agencies and hospitals to enhance syndromic surveillance, communicable disease management, and public health emergency preparedness and response. This comprehensive description of the program and its value to stakeholders, both in routine daily practice and in responding to a major public health emergency, can inform other states that may wish to establish a similar program as part of their larger public health emergency preparedness and response system.
Apoptosis inhibition or inflammation: the role of NAIP protein expression in Hodgkin and non-Hodgkin lymphomas compared to non-neoplastic lymph node
Authors: Mazrouei Safoura , Ziaei Amin , Tanhaee Amir Pouya , Keyhanian Kianoosh , Esmaeili Mahdad , Baradaran Azar , Salehi Mansoor
Published: February 2012

Background

Inhibitors of Apoptosis (IAP) family play a critical role in apoptosis and inflammatory response. Neuronal Apoptosis Inhibitory Protein (NAIP), as a member of both IAPs and NLR families (NOD-Like Receptor), is a unique IAP harboring NOD (Nucleotide Oligomerization Domain) and LLR (Leucine Rich Repeat) motifs. Considering these motifs in NAIP, it has been suggested that the main function of NAIP is distinct from other members of IAPs. As a member of NLR, NAIP mediates the assembly of 'Inflammasome' for inflammatory caspase activation. Pathologic expression of NAIP has been reported not only in some infectious and inflammatory diseases but also in some malignancies. However, there is no report to elucidate NAIP expression in lymphomatic malignancies.

Methods

In this study, we examined NAIP protein expression in 101 Formalin-Fixed Paraffin-Embedded blocks including samples from 39 Hodgkin Lymphoma and 23 Non Hodgkin Lymphoma cases in comparison with 39 control samples (30 normal and 9 Reactive Lymphoid Hyperplasia (RLH) lymph nodes) using semi-quantitative immuno-flourecent Staining.

Results

NAIP expression was not statistically different in lymphoma samples neither in HL nor in NHL cases comparing to normal samples. However, we evaluated NAIP expression in normal and RLH lymph nodes. Surprisingly, we have found a statistically significant-difference between the NAIP expression in RLH (M.R of NAIP/GAPDH expression = 0.6365 ± 0.017) and normal lymph node samples (M.R of NAIP/GAPDH expression = 0.5882 ± 0.047) (P < 0.01).

Conclusions

These findings show that the regulation of apoptosis could not be the main function of NAIP in the cell, so the pathologic expression of NAIP is not involved in lymphoma. But, we concluded that the over expression of NAIP has more effective role in the inflammatory response. Also, this study clarifies the NAIP expression level in lymphoma which is required for IAPs profiling in order to be used in potential translational applications of IAPs.
Fabrication mechanism of friction-induced selective etching on Si(100) surface
Authors: Guo Jian , Song Chenfei , Li Xiaoying , Yu Bingjun , Dong Hanshan , Qian Linmao , Zhou Zhongrong
Published: February 2012

As a maskless nanofabrication technique, friction-induced selective etching can easily produce nanopatterns on a Si(100) surface. Experimental results indicated that the height of the nanopatterns increased with the KOH etching time, while their width increased with the scratching load. It has also found that a contact pressure of 6.3 GPa is enough to fabricate a mask layer on the Si(100) surface. To understand the mechanism involved, the cross-sectional microstructure of a scratched area was examined, and the mask ability of the tip-disturbed silicon layer was studied. Transmission electron microscope observation and scanning Auger nanoprobe analysis suggested that the scratched area was covered by a thin superficial oxidation layer followed by a thick distorted (amorphous and deformed) layer in the subsurface. After the surface oxidation layer was removed by HF etching, the residual amorphous and deformed silicon layer on the scratched area can still serve as an etching mask in KOH solution. The results may help to develop a low-destructive, low-cost, and flexible nanofabrication technique suitable for machining of micro-mold and prototype fabrication in micro-systems.
Provider and clinic‐level correlates of deferring antiretroviral therapy for people who inject drugs: a survey of North American HIV providers
Authors: Westergaard Ryan P , Ambrose Bridget K , Mehta Shruti H , Kirk Gregory D
Published: February 2012

Background

Injection drug users (IDUs) face numerous obstacles to receiving optimal HIV care, and have been shown to underutilize antiretroviral therapy (ART). We sought to estimate the degree to which providers of HIV care defer initiation of ART because of injection drug use and to identify clinic and provider‐level factors associated with resistance to prescribing ART to IDUs.

Methods

We administered an Internet‐based survey to 662 regular prescribers of ART in the United States and Canada. Questionnaire items assessed characteristics of providers' personal demographics and training, site of clinical practice and attitudes about drug use. Respondents then rated whether they would likely prescribe or defer ART for hypothetical patients in a series of scenarios involving varying levels of drug use and HIV disease stage.

Results

Survey responses were received from 43% of providers invited by email and direct mail, and 8.5% of providers invited by direct mail only. Overall, 24.2% of providers reported that they would defer ART for an HIV‐infected patient with a CD4+ cell count of 200 cells/mm3 if the patient actively injected drugs, and 52.4% would defer ART if the patient injected daily. Physicians were more likely than non‐physician providers to defer ART if a patient injected drugs (adjusted odds ratio 2.6, 95% CI 1.4‐4.9). Other predictors of deferring ART for active IDUs were having fewer years of experience in HIV care, regularly caring for fewer than 20 HIV‐infected patients, and working at a clinic serving a population with low prevalence of injection drug use. Likelihood of deferring ART was directly proportional to both CD4+ cell count and increased frequency of injecting.

Conclusions

Many providers of HIV care defer initiation of antiretroviral therapy for patients who inject drugs, even in the setting of advanced immunologic suppression. Providers with more experience of treating HIV, those in high injection drug use prevalence areas and non‐physician providers may be more willing to prescribe ART despite on‐going injection drug use. Because of limitations, including low response rate and use of a convenience sample, these findings may not be generalizable to all HIV care providers in North America.
Functional magnetic resonance imaging correlates of memory encoding in relation to achieving remission in first-episode schizophrenia
Authors: Bodnar Michael , Achim Amelie M. , Malla Ashok K. , Joober Ridha , Benoit Audrey , Lepage Martin
Published: February 2012

Background

Previous studies in schizophrenia have shown a strong relationship between memory deficits and a poor clinical outcome. However, no previous study has identified the functional neural correlates of memory encoding in relation to remission.

Aims

To determine whether functional magnetic resonance imaging (fMRI) activation patterns differed between individuals that later achieved remission v. those who did not.

Method

Forty-two participants with first-episode schizophrenia were divided into two groups after 1 year of treatment as per the 2005 remission in schizophrenia consensus definition. We then examined fMRI activation using three contrasts (associative v. item-oriented strategy, semantically unrelated v. related image pairs, and successful v. unsuccessful memory encoding) among 15 participants who had achieved remission (remitted group), 27 who had not (non-remitted group) and 31 healthy controls (control group).

Results

Participants in the non-remitted group displayed a positive activation in the posterior cingulate compared with those in the remitted group when encoding related images; no significant differences between the two groups were identified for the other contrasts. From the behavioural data, compared with the remitted and control groups, the non-remitted group demonstrated an inability to encode related images and displayed worse recognition memory overall.

Conclusions

This is the first study to identify differential neural activation between individuals with first-episode schizophrenia that later achieved remission v. those who did not. The behavioural and functional results together add to the growing evidence relating a poor clinical outcome in schizophrenia to memory-related deficits.
bHLH-O proteins are crucial for Drosophila neuroblast self-renewal and mediate Notch-induced overproliferation
Authors: Zacharioudaki Evanthia , Magadi Srivathsa S. , Delidakis Christos
Published: February 2012

Drosophila larval neurogenesis is an excellent system for studying the balance between self-renewal and differentiation of a somatic stem cell (neuroblast). Neuroblasts (NBs) give rise to differentiated neurons and glia via intermediate precursors called GMCs or INPs. We show that E(spl)mγ, E(spl)mβ, E(spl)m8 and Deadpan (Dpn), members of the basic helix-loop-helix-Orange protein family, are expressed in NBs but not in differentiated cells. Double mutation for the E(spl) complex and dpn severely affects the ability of NBs to self-renew, causing premature termination of proliferation. Single mutations produce only minor defects, which points to functional redundancy between E(spl) proteins and Dpn. Expression of E(spl)mγ and m8, but not of dpn, depends on Notch signalling from the GMC/INP daughter to the NB. When Notch is abnormally activated in NB progeny cells, overproliferation defects are seen. We show that this depends on the abnormal induction of E(spl) genes. In fact E(spl) overexpression can partly mimic Notch-induced overproliferation. Therefore, E(spl) and Dpn act together to maintain the NB in a self-renewing state, a process in which they are assisted by Notch, which sustains expression of the E(spl) subset.
Vimentin regulates peripheral nerve myelination
Authors: Triolo Daniela , Dina Giorgia , Taveggia Carla , Vaccari Ilaria , Porrello Emanuela , Rivellini Cristina , Domi Teuta , La Marca Rosa , Cerri Federica , Bolino Alessandra , Quattrini Angelo , Previtali Stefano Carlo
Published: February 2012

Myelination is a complex process that requires coordinated Schwann cell-axon interactions during development and regeneration. Positive and negative regulators of myelination have been recently described, and can belong either to Schwann cells or neurons. Vimentin is a fibrous component present in both Schwann cell and neuron cytoskeleton, the expression of which is timely and spatially regulated during development and regeneration. We now report that vimentin negatively regulates myelination, as loss of vimentin results in peripheral nerve hypermyelination, owing to increased myelin thickness in vivo, in transgenic mice and in vitro in a myelinating co-culture system. We also show that this is due to a neuron-autonomous increase in the levels of axonal neuregulin 1 (NRG1) type III. Accordingly, genetic reduction of NRG1 type III in vimentin-null mice rescues hypermyelination. Finally, we demonstrate that vimentin acts synergistically with TACE, a negative regulator of NRG1 type III activity, as shown by hypermyelination of double Vim/Tace heterozygous mice. Our results reveal a novel role for the intermediate filament vimentin in myelination, and indicate vimentin as a regulator of NRG1 type III function.
Differential regulation of node formation, nodal ciliogenesis and cilia positioning by Noto and Foxj1
Authors: Alten Leonie , Schuster-Gossler Karin , Beckers Anja , Groos Stephanie , Ulmer Bärbel , Hegermann Jan , Ochs Matthias , Gossler Achim
Published: February 2012

The mouse transcription factor Noto is expressed in the node and controls node morphogenesis, formation of nodal cilia and left-right asymmetry. Noto acts upstream of Foxj1, which regulates ciliogenesis in other mouse tissues. However, the significance of Foxj1 for the formation of cilia in the mouse node is unclear; in non-amniote species Foxj1 is required for ciliogenesis in the structures equivalent to the node. Here, we analyzed nodes, nodal cilia and nodal flow in mouse embryos in which we replaced the Noto-coding sequence with that of Foxj1, or in embryos that were deficient for Foxj1. We show that Foxj1 expressed from the Noto locus is functional and restores the formation of structurally normal motile cilia in the absence of Noto. However, Foxj1 is not sufficient for the correct positioning of cilia on the cell surface within the plane of the nodal epithelium, and cannot restore normal node morphology. We also show that Foxj1 is essential for ciliogenesis upstream of Rfx3 in the node. Thus, the function of Foxj1 in vertebrate organs of asymmetry is conserved, and Noto regulates node morphogenesis and the posterior localization of cilia on node cells independently of Foxj1.
Evolution of self-organisation in Dictyostelia by adaptation of a non-selective phosphodiesterase and a matrix component for regulated cAMP degradation
Authors: Kawabe Yoshinori , Weening Karin E. , Marquay-Markiewicz Jacques , Schaap Pauline
Published: February 2012

Dictyostelium discoideum amoebas coordinate aggregation and morphogenesis by secreting cyclic adenosine monophosphate (cAMP) pulses that propagate as waves through fields of cells and multicellular structures. To retrace how this mechanism for self-organisation evolved, we studied the origin of the cAMP phosphodiesterase PdsA and its inhibitor PdiA, which are essential for cAMP wave propagation. D. discoideum and other species that use cAMP to aggregate reside in group 4 of the four major groups of Dictyostelia. We found that groups 1-3 express a non-specific, low affinity orthologue of PdsA, which gained cAMP selectivity and increased 200-fold in affinity in group 4. A low affinity group 3 PdsA only partially restored aggregation of a D. discoideum pdsA-null mutant, but was more effective at restoring fruiting body morphogenesis. Deletion of a group 2 PdsA gene resulted in disruption of fruiting body morphogenesis, but left aggregation unaffected. Together, these results show that groups 1-3 use a low affinity PdsA for morphogenesis that is neither suited nor required for aggregation. PdiA belongs to a family of matrix proteins that are present in all Dictyostelia and consist mainly of cysteine-rich repeats. However, in its current form with several extensively modified repeats, PdiA is only present in group 4. PdiA is essential for initiating spiral cAMP waves, which, by organising large territories, generate the large fruiting structures that characterise group 4. We conclude that efficient cAMP-mediated aggregation in group 4 evolved by recruitment and adaptation of a non-selective phosphodiesterase and a matrix component into a system for regulated cAMP degradation.
The conserved transcription factor Mef2 has multiple roles in adult Drosophila musculature formation
Authors: Soler Cedric , Han Jun , Taylor Michael V.
Published: February 2012

Muscle is an established paradigm for analysing the cell differentiation programs that underpin the production of specialised tissues during development. These programs are controlled by key transcription factors, and a well-studied regulator of muscle gene expression is the conserved transcription factor Mef2. In vivo, Mef2 is essential for the development of the Drosophila larval musculature: Mef2-null embryos have no differentiated somatic muscle. By contrast, a similar phenotype has not been seen in analyses of the function of Mef2 genes in other examples of myogenesis. These include using conditional mutant mice, using morpholinos in zebrafish and using hypomorphic mutants in Drosophila adult development. However, we show here that Mef2 is absolutely required for a diverse range of Drosophila adult muscle types. These include the dorso-longitudinal muscles (DLMs), the largest flight muscles, which are produced by tissue remodelling. Furthermore, we demonstrate that Mef2 has temporally separable functions in this remodelling and in muscle maintenance. Drosophila adult muscles are multi-fibre and physiologically diverse, in common with vertebrate skeletal muscles, but in contrast to Drosophila larval muscles. These results therefore establish the importance of Mef2 in multiple roles in examples of myogenesis that have parallels in vertebrates and are distinct from that occurring in Drosophila embryogenesis.
2-O-sulfotransferase regulates Wnt signaling, cell adhesion and cell cycle during zebrafish epiboly
Authors: Cadwalader Erin L. , Condic Maureen L. , Yost H. Joseph
Published: February 2012

O-sulfotransferases modify heparan sulfate proteoglycans (HSPGs) by catalyzing the transfer of a sulfate to a specific position on heparan sulfate glycosaminoglycan (GAG) chains. Although the roles of specific HSPG modifications have been described in cell culture and invertebrates, little is known about their functions or abilities to modulate specific cell signaling pathways in vertebrate development. Here, we report that 2-O-sulfotransferase (2-OST) is an essential component of canonical Wnt signaling in zebrafish development. 2-OST-defecient embryos have reduced GAG chain sulfation and are refractory to exogenous Wnt8 overexpression. Embryos in which maternally encoded 2-OST is knocked down have normal activation of several zygotic mesoderm, endoderm and ectoderm patterning genes, but have decreased deep cell adhesion and fail to initiate epiboly, which can be rescued by re-expression of 2-OST protein. Reduced cell adhesion and altered cell cycle regulation in 2-OST-deficient embryos are associated with decreased β-catenin and E-cadherin protein levels at cell junctions, and these defects can be rescued by reactivation of the intracellular Wnt pathway, utilizing stabilized β-catenin or dominant-negative Gsk3, but not by overexpression of Wnt8 ligand. Together, these results indicate that 2-OST functions within the Wnt pathway, downstream of Wnt ligand signaling and upstream of Gsk3β and β-catenin intracellular localization and function.
SNAREs, HOPS, and regulatory lipids control the dynamics of vacuolar actin during homotypic fusion
Authors: Karunakaran Surya , Sasser Terry , Rajalekshmi Sailasree , Fratti Rutilio A.
Published: February 2012

Homotypic vacuole fusion requires SNAREs, the Rab Ypt7p, the tethering complex HOPS, regulatory lipids, and actin. In Saccharomyces cerevisiae, actin functions at two stages of vacuole fusion. Pre-existing actin filaments are depolymerized to allow docking and assembly of the vertex ring; a microdomain enriched in proteins and lipids that mediate fusion. Actin is then polymerized late in the pathway to aid fusion. Here, we report that the fusion machinery regulates the accumulation of actin at the vertex ring. Using Cy3-labeled yeast actin to track its dynamics, we found that its vertex enrichment was abolished when actin monomers were stabilized by latrunculin-B, independent of the extent of incorporation. In contrast, stabilization of filamentous actin with jasplakinolide markedly augmented actin vertex enrichment. Importantly, agents that inhibit SNAREs, Ypt7p and HOPS inhibited the vertex enrichment of actin, demonstrating that the cytoskeleton and the fusion machinery are interdependently regulated. Actin mobilization was also inhibited by ligating ergosterol and PI3P, whereas the ligation or modification of PI(4,5)P2 augmented the vertex enrichment of actin. The proteins and lipids that regulated actin mobilization to the vertex did not affect the total incorporation of Cy3-actin, indicating that actin mobilization and polymerization activities can be dissociated during membrane fusion.
Disruption of Kif3a in osteoblasts results in defective bone formation and osteopenia
Authors: Qiu Ni , Xiao Zhousheng , Cao Li , Buechel Meagan M. , David Valentin , Roan Esra , Quarles L. Darryl
Published: February 2012

We investigated whether Kif3a in osteoblasts has a direct role in regulating postnatal bone formation. We conditionally deleted Kif3a in osteoblasts by crossing Osteocalcin (Oc)-Cre with Kif3aflox/null mice. Conditional Kif3a null mice (Kif3aOc-cKO) had a 75% reduction in Kif3a transcripts in bone and osteoblasts. Conditional deletion of Kif3a resulted in the reduction of primary cilia number by 51% and length by 27% in osteoblasts. Kif3aOc-cKO developed osteopenia by 6 weeks-of- age compared with Kif3aflox/+ control mice, as evidenced by reductions in femoral bone mineral density (22%); trabecular bone volume (42%); and cortical thickness (17%). In contrast, Oc-Cre;Kif3aflox/+ and Kif3aflox/null heterozygous mice exhibited no skeletal abnormalities. Loss of bone mass in Kif3aOc-cKO mice was associated with impaired osteoblast function in vivo, as reflected by a 54% reduction in mineral apposition rate and decreased expression of Runx2, Osterix, Osteocalcin, and Dmp1 compared to controls. Immortalized osteoblasts from Kif3aOc-cKO mice exhibited increased cell proliferation, impaired osteoblastic differentiation, and enhanced adipogenesis in vitro. Osteoblasts derived from Kif3aOc-cKO mice also had lower basal cytosolic calcium levels and impaired intracellular calcium responses to fluid flow shear stress. Sonic hedgehog-mediated Gli2 expression and Wnt3a-mediated β-catenin/Axin2 expression were also attenuated in Kif3aOc-cKO bone and osteoblast cultures. These data indicate that selective deletion of Kif3a in osteoblasts disrupts primary cilia formation/function and impairs osteoblast-mediated bone formation through multiple pathways including intracellular calcium, hedgehog, and Wnt signaling.
Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration
Authors: Suzuki Mihoko , Tsujikawa Motokazu , Itabe Hiroyuki , Du Zhao-Jiang , Xie Ping , Matsumura Nagakazu , Fu Xiaoming , Zhang Renliang , Sonoda Koh-hei , Egashira Kensuke , Hazen Stanley L. , Kamei Motohiro
Published: February 2012

Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Although pathogenic factors, such as oxidative stress, inflammation, and genetics are thought to contribute to the development of AMD, little is known about the relationships and priorities between these factors. Here, we show that chronic photo-oxidative stress is an environmental factor involved in AMD pathogenesis. We first demonstrated that light exposure induced phospholipid oxidation in the mouse retina, which was more prominent in aged animals. The induced oxidized phospholipids led to an increase in the expression of monocyte chemoattractant protein-1, which then resulted in macrophage accumulation, an inflammatory process. Antioxidant treatment prevented light-induced phospholipid oxidation and the subsequent increase of monocyte chemoattractant protein-1, which are the beginnings of the light-induced changes. Subretinal application of oxidized phospholipids induced choroidal neovascularization, a characteristic feature of wet-type AMD, which was inhibited by blocking monocyte chemoattractant protein-1. These findings strongly suggest that a sequential cascade from photic stress to inflammatory processes via phospholipid oxidation has an important role in AMD pathogenesis. Finally, we succeeded in mimicking human AMD in mice with low level, long-term photic stress, in which characteristic pathological changes, including choroidal neovascularization formation, were observed. Therefore, we propose a consecutive pathogenic pathway involving photic stress, oxidation of phospholipids, and chronic inflammation, leading to angiogenesis. These findings add to the current understanding of AMD pathology and suggest protection from oxidative stress or suppression of the subsequent inflammation as new potential therapeutic targets for AMD.
VANGL2 regulates membrane trafficking of MMP14 to control cell polarity and migration
Authors: Williams B. Blairanne , Cantrell V. Ashley , Mundell Nathan A. , Bennett Andrea C. , Quick Rachel E. , Jessen Jason R.
Published: February 2012

Planar cell polarity (PCP) describes the polarized orientation of cells within the plane of a tissue. Unlike epithelial PCP, the mechanisms underlying PCP signaling in migrating cells remain undefined. Here, the establishment of PCP must be coordinated with dynamic changes in cell adhesion and extracellular matrix (ECM) organization. During gastrulation, membrane type-1 matrix metalloproteinase (MMP14/MT1-MMP) is required for PCP and convergence and extension cell movements. We report that the PCP protein Vang-like 2 (VANGL2) regulates the endocytosis and cell surface availability of MMP14 in a focal adhesion kinase dependent manner. We demonstrate that zebrafish trilobite/vangl2 mutant embryos exhibit increased Mmp14 activity and decreased ECM. Furthermore, in vivo knockdown of Mmp14 partially rescues the Vangl2 loss of function convergence and extension phenotype. This study identifies a novel mechanism linking VANGL2 with MMP14 trafficking and suggests that establishment of PCP in migrating gastrula cells requires regulated proteolytic degradation/remodeling of ECM. Our findings implicate matrix metalloproteinases as downstream effectors of PCP and suggest a broadly applicable mechanism whereby VANGL2 affects diverse morphogenetic processes.
Sub-diffraction imaging on standard microscopes through Photobleaching Microscopy with non-linear Processing
Authors: Munck Sebastian , Miskiewicz Katarzyna , Sannerud Ragna , Menchon Silvia A. , Jose Liya , Heintzmann Rainer , Verstreken Patrik , Annaert Wim
Published: February 2012

Discerning organelles and molecules at nanometer resolution is revolutionizing biological sciences. However, such technology is still limitedly available for many cell biologists. We present here a novel approach using Photobleaching Microscopy with non-linear Processing (PiMP) for sub-diffraction imaging. Bleaching fluorophores both within the single molecule regime and beyond allows visualizing stochastic representations of sub-populations of fluorophores by imaging the same region over time. Our method is based on enhancing probable positions of the fluorophores underlying the images. The random nature of the bleached fluorophores is assessed by calculating the deviation of the local actual bleached fluorescence intensity to the average bleach expectation as given by the overall decay of intensity. Subtracting measured from estimated decay images yields differential images. Non-linear enhancement of maxima in these diffraction limited differential images approximates the positions of the underlying structure. Summing many such processed differential images yields a super-resolution PiMP image. PiMP allows multi-color, three-dimensional sub-diffraction imaging of cells and tissues using common fluorophores and can be implemented on standard widefield or confocal systems.