bluuebunny/crossref_metadata_2025 huggingface dataset:
Managing intimate partner violence at the social services department of a Greek university hospital
Authors: Papadakaki Maria , Kastrinaki Eirini , Drakaki Renanthi , Chliaoutakis Joannes
Published: February 2012

• Summary:

Although abused patients are thought to access the health system at a range of potential entry points, social services are usually the only referral option within the various hospital sectors. In Greece, little is known about the prevalence of intimate partner violence (IPV) and the quality of care provided to cases of abuse at the social services. The current study explored the department’s response to IPV cases in a Greek university hospital. Two different research methods were employed: qualitative and document research. Qualitative data were collected through personal interviews with the 10 social workers employed at the department. Document research involved the review of all registries and social history forms recorded between January 2005 and April 2009 at the department. Two predefined screening criteria were employed to identify IPV cases. Seven socio-demographic variables were abstracted from all IPV cases that met the inclusion criteria.

• Findings:

Four main themes emerged from the qualitative analysis: 1) knowledge gap and openness to education, 2) poor assessment and recording practices, 3) concerns about intervention in confirmed cases, and 4) mistrust in referral resources. The document research revealed a total of 42 records (3.8%) having an IPV screening record present, out of the 1117 initially reviewed. The majority of the IPV patients were women ( n = 33, 78.6%), encountered at the age group of 28–37 years ( n = 16, 38.1%) and presented mixed types of abuse ( n = 32, 76.2%).

• Applications:

Developing training opportunities and introducing organizational changes could help social workers to better manage IPV cases in the hospital setting.
Integrative Psychodynamic Treatment of Ataque de Nervios
Authors: Sanchez Adrian , Shallcross Robin
Published: February 2012

With the evolving demographics in the U.S. population, Latinos are the largest racial/ethnic community in the United States and face many barriers to psychological well-being and overall health. Some Latinos present with culturally influenced idioms of distress such as ataque de nervios. Associations between ataque de nervios and a range of social and psychiatric vulnerabilities among Latinos living on the United States mainland have been found. An integrative, trauma-informed, and culturally sensitive psychodynamic perspective can help with understanding and treating ataque de nervios. This case study presents the treatment of a young undocumented Latina mother experiencing ataque de nervios. A psychodynamic approach, integrated with narrative therapy and cognitive-behavioral therapy techniques, is illustrated.
Differential Effects of Power Training Versus Functional Task Practice on Compensation and Restoration of Arm Function After Stroke
Authors: Corti Manuela , McGuirk Theresa E. , Wu Samuel S. , Patten Carolynn
Published: February 2012

Background. Improved upper-extremity (UE) movement with stroke rehabilitation may involve restoration of more normal or development of compensatory movement patterns. Objective. The authors investigated the differential effects of functional task practice (FTP) and dynamic resistance training (POWER) on clinical function and reaching kinematics in an effort to distinguish between mechanisms of gains. Methods. A total of 14 hemiparetic individuals were randomly assigned to 10 weeks of either FTP or POWER and then crossed over to 10 weeks of the alternate treatment. Treatment order A was FTP followed by POWER, whereas treatment order B was POWER followed by FTP. Evaluation before and after each treatment block included a battery of clinical evaluations and kinematics of paretic UE functional reach to grasp. Results. Both FTP and POWER improved movement accuracy, as revealed by a shift toward normal, including fewer submovements and reduced reach-path ratio. However, active range of motion revealed differential treatment effects. Shoulder flexion and elbow extension decreased with FTP and were associated with increased trunk displacement. In contrast, shoulder flexion and elbow extension excursion increased with POWER and were associated with significantly reduced trunk displacement. Treatment order B (POWER followed by FTP) revealed greater overall improvements. Conclusion. FTP increases compensatory movement patterns to improve UE function. POWER leads to more normal movement patterns. POWER prior to FTP may enhance the benefits of repetitive task practice.
Simulating Light Source Motion in Single Images for Enhanced Perceptual Object Detection
Authors: Hirsch Herb L , Moore Cathleen M
Published: February 2012

The SIPHER technique uses mathematically-uncomplicated processing to impart interesting effects upon a static image. Importantly, it renders certain areas of an image more perceptible than others, and draws a human observer’s attention to particular objects or portions of an image scene. By varying coefficients of the processing in a time-ordered sequence, we can create a multi-frame video wherein the frame-to-frame temporal dynamics further enhance human perception of image objects. In this article we first explain the mathematical formulations and present results from applying SIPHER to simple three-dimensional shapes. Then we explore SIPHER’s utility in enhancing visual perception of targets or objects of military interest, in imagery with some typical backgrounds. We also explore how and why these effects enhance human visual perception of the image objects.
Lolita speaks: ‘Sexting,’ teenage girls and the law
Authors: Karaian Lara
Published: February 2012

Recently, national and local media across North America have warned against the risks of ‘sexting’ – the practice of sending, posting or possessing sexually suggestive text messages and images via cell phones or the Internet. In response to this phenomenon, Pennsylvania District Attorney Skumanick threatened to bring child pornography charges against teenagers who had been caught sexting and who refused to attend a gender-based ‘re-education’ program designed to teach them about its dangers. Three girls refused the ultimatum, resulting in Miller v. Mitchell [2010], the first case to challenge the constitutionality of prosecuting teens for their digital sexual expression. This article critically considers dominant and intersecting cultural and legal narratives about sexting and troubles the predominant construction of teenage female sexters as dupes of the ‘pornification’ of a generation and as ‘self-sexually exploiting.’ The cultural and legal disavowal of girls’ narratives about digital sexual expression is considered through Judith Butler’s poststructural analysis of sexuality, speech and censorship. Drawing on two online studies of sexting, contributions to an online forum on the topic, and third-wave feminist writings on a generational re-envisioning of risk, respectability and privacy, I argue that that the foreclosure of the ‘domain of the sayable’ within which girls seek to speak works paradoxically to further render them fetishized sexual objects, thus engendering the very harm that criminal law seeks to remedy.
Interdisciplinary approach to the demography of Jamaica
Authors: Deason Michael L , Salas Antonio , Newman Simon P , Macaulay Vincent A , st A Morrison Errol Y , Pitsiladis Yannis P
Published: February 2012

Background

The trans-Atlantic slave trade dramatically changed the demographic makeup of the New World, with varying regions of the African coast exploited differently over roughly a 400 year period. When compared to the discrete mitochondrial haplotype distribution of historically appropriate source populations, the unique distribution within a specific source population can prove insightful in estimating the contribution of each population. Here, we analyzed the first hypervariable region of mitochondrial DNA in a sample from the Caribbean island of Jamaica and compared it to aggregated populations in Africa divided according to historiographically defined segments of the continent's coastline. The results from these admixture procedures were then compared to the wealth of historic knowledge surrounding the disembarkation of Africans on the island.

Results

In line with previous findings, the matriline of Jamaica is almost entirely of West African descent. Results from the admixture analyses suggest modern Jamaicans share a closer affinity with groups from the Gold Coast and Bight of Benin despite high mortality, low fecundity, and waning regional importation. The slaves from the Bight of Biafra and West-central Africa were imported in great numbers; however, the results suggest a deficit in expected maternal contribution from those regions.

Conclusions

When considering the demographic pressures imposed by chattel slavery on Jamaica during the slave era, the results seem incongruous. Ethnolinguistic and ethnographic evidence, however, may explain the apparent non-random levels of genetic perseverance. The application of genetics may prove useful in answering difficult demographic questions left by historically voiceless groups.
Antiadhesive activity of the biosurfactant pseudofactin II secreted by the Arctic bacterium Pseudomonas fluorescensBD5
Authors: Janek Tomasz , Łukaszewicz Marcin , Krasowska Anna
Published: February 2012

Background

Pseudofactin II is a recently identified biosurfactant secreted by Pseudomonas fluorescens BD5, the strain obtained from freshwater from the Arctic Archipelago of Svalbard. Pseudofactin II is a novel compound identified as cyclic lipopeptide with a palmitic acid connected to the terminal amino group of eighth amino acid in peptide moiety. The C-terminal carboxylic group of the last amino acid forms a lactone with the hydroxyl of Thr3.

Adhesion is the first stage of biofilm formation and the best moment for the action of antiadhesive and anti-biofilm compounds. Adsorption of biosurfactants to a surface e.g. glass, polystyrene, silicone modifies its hydrophobicity, interfering with the microbial adhesion and desorption processes. In this study the role and applications of pseudofactin II as a antiadhesive compound has been investigated from medicinal and therapeutic perspectives.

Results

Pseudofactin II lowered the adhesion to three types of surfaces (glass, polystyrene and silicone) of bacterial strains of five species: Escherichia coli, Enterococcus faecalis, Enterococcus hirae, Staphylococcus epidermidis, Proteus mirabilis and two Candida albicans strains. Pretreatment of a polystyrene surface with 0.5 mg/ml pseudofactin II inhibited bacterial adhesion by 36-90% and that of C. albicans by 92-99%. The same concentration of pseudofactin II dislodged 26-70% of preexisting biofilms grown on previously untreated surfaces. Pseudofactin II also caused a marked inhibition of the initial adhesion of E. faecalis, E. coli, E. hirae and C. albicans strains to silicone urethral catheters. The highest concentration tested (0.5 mg/ml) caused a total growth inhibition of S. epidermidis, partial (18-37%) inhibition of other bacteria and 8-9% inhibition of C. albicans growth.

Conclusion

Pseudofactin II showed antiadhesive activity against several pathogenic microorganisms which are potential biofilm formers on catheters, implants and internal prostheses. Up to 99% prevention could be achieved by 0.5 mg/ml pseudofactin II. In addition, pseudofactin II dispersed preformed biofilms. Pseudofactin II can be used as a disinfectant or surface coating agent against microbial colonization of different surfaces, e.g. implants or urethral catheters.
Bioinformatic identification of cassava miRNAs differentially expressed in response to infection by Xanthomonas axonopodis pv. manihotis
Authors: Pérez-Quintero Álvaro L , Quintero Andrés , Urrego Oscar , Vanegas Pablo , López Camilo
Published: February 2012

Background

microRNAs (miRNAs) are short RNA molecules that control gene expression by silencing complementary mRNA. They play a crucial role in stress response in plants, including biotic stress. Some miRNAs are known to respond to bacterial infection in Arabidopsis thaliana but it is currently unknown whether these responses are conserved in other plants and whether novel species-specific miRNAs could have a role in defense.

Results

This work addresses the role of miRNAs in the Manihot esculenta (cassava)-Xanthomonas axonopodis pv. manihotis (Xam) interaction. Next-generation sequencing was used for analyzing small RNA libraries from cassava tissue infected and non-infected with Xam. A full repertoire of cassava miRNAs was characterized, which included 56 conserved families and 12 novel cassava-specific families. Endogenous targets were predicted in the cassava genome for many miRNA families. Some miRNA families' expression was increased in response to bacterial infection, including miRNAs known to mediate defense by targeting auxin-responding factors as well as some cassava-specific miRNAs. Some bacteria-repressed miRNAs included families involved in copper regulation as well as families targeting disease resistance genes. Putative transcription factor binding sites (TFBS) were identified in the MIRNA genes promoter region and compared to promoter regions in miRNA target genes and protein coding genes, revealing differences between MIRNA gene transcriptional regulation and other genes.

Conclusions

Taken together these results suggest that miRNAs in cassava play a role in defense against Xam, and that the mechanism is similar to what's known in Arabidopsis and involves some of the same families.
Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids: importance of the mitochondrial function
Authors: Martins Amanda R , Nachbar Renato T , Gorjao Renata , Vinolo Marco A , Festuccia William T , Lambertucci Rafael H , Cury-Boaventura Maria F , Silveira Leonardo R , Curi Rui , Hirabara Sandro M
Published: February 2012

Insulin resistance condition is associated to the development of several syndromes, such as obesity, type 2 diabetes mellitus and metabolic syndrome. Although the factors linking insulin resistance to these syndromes are not precisely defined yet, evidence suggests that the elevated plasma free fatty acid (FFA) level plays an important role in the development of skeletal muscle insulin resistance. Accordantly, in vivo and in vitro exposure of skeletal muscle and myocytes to physiological concentrations of saturated fatty acids is associated with insulin resistance condition. Several mechanisms have been postulated to account for fatty acids-induced muscle insulin resistance, including Randle cycle, oxidative stress, inflammation and mitochondrial dysfunction. Here we reviewed experimental evidence supporting the involvement of each of these propositions in the development of skeletal muscle insulin resistance induced by saturated fatty acids and propose an integrative model placing mitochondrial dysfunction as an important and common factor to the other mechanisms.
Cellular transcripts of chicken brain tissues in response to H5N1 and Newcastle disease virus infection
Authors: Balasubramaniam Vinod RMT , Wai Tham H , Omar Abdul R , Othman Iekhsan , Hassan Sharifah S
Published: February 2012

Background

Highly-pathogenic avian influenza (HPAI) H5N1 and Newcastle disease (ND) viruses are the two most important poultry viruses in the world, with the ability to cause classic central nervous system dysfunction in poultry and migratory birds. To elucidate the mechanisms of neurovirulence caused by these viruses, a preliminary study was design to analyze host's cellular responses during infections of these viruses.

Methods

An improved mRNA differential display technique (Gene Fishing™) was undertaken to analyze differentially expressed transcripts regulated during HPAI H5N1 and velogenic neurotropic NDV infections of whole brain of chickens. The identification of differentially expressed genes (DEGs) was made possible as this technique uses annealing control primers that generate reproducible, authentic and long PCR products that are detectable on agarose gels.

Results

Twenty-three genes were identified to be significantly regulated during infections with both viruses, where ten of the genes have been selected for validation using a TaqMan® based real time quantitative PCR assay. Some of the identified genes demonstrated to be key factors involving the cytoskeletal system, neural signal transduction and protein folding during stress. Interestingly, Septin 5, one of the genes isolated from HPAI H5N1-infected brain tissues has been reported to participate in the pathogenic process of Parkinson's disease.

Conclusions

In this limited study, the differentially expressed genes of infected brain tissues regulated by the viruses were found not to be identical, thus suggesting that their neurovirulence and neuropathogenesis may not share similar mechanisms and pathways.
Molecular characterization of human calicivirus associated with acute diarrheal disease in mexican children
Authors: Gómez-Santiago Fabián , Ribas-Aparicio Rosa María , García-Lozano Herlinda
Published: February 2012

Background

Human caliciviruses (HuCV) are emerging enteric pathogens that are a common cause of diarrhea in humans worldwide. Due to the paucity of information on the molecular characterization of HuCV circulating in Mexico, the aim of this work was to investigate the diversity and molecular epidemiology of the HuCV infection associated with acute diarrheal disease in Mexican children aged up to 5 years.

Results

Of the 131/414 (32%) HuCV positive-specimens analyzed, 128 were identified as Norovirus (NoV) and three as Sapovirus (SaV). Of the NoV positive specimens, 118/128 (92%) were NoV GII and 10/128(8%) were untypeable by RT-PCR in both polymerase and capsid genes, whereas one SaV isolate was further confirmed by sequencing as GI.2. Phylogenetic analysis based on polymerase partial gene sequences from 89/131 (68%) HuCV isolates showed that 86/89 (97%) belong to NoV GII.4 with three main variant clusters of this genotype, 2/89 (2%) to NoV GII.2, and 1/89 (1%) to SaV GI.2. Furthermore, partial sequencing of the capsid gene VP1 of 63/131 (48%) strains indicated that 61/63 (97%) correlated with NoV GII.4, whereas only 2/63 (3%) clustered to NoV GII.2. HuCV infections were detected throughout the year, and the highest number of cases positive for NoV was found in children between 7 and 18 months of age (60%).

Conclusions

This study highlights the usefulness of analyzing both polymerase and capsid genes for molecular characterization of HuCV and demonstrates the relatedness and predominance of NoV GII.4 with acute diarrheal disease in young Mexican children, thus contributing to better understanding of the molecular epidemiology of this disease.
Efficacy of early neonatal vitamin A supplementation in reducing mortality during infancy in Ghana, India and Tanzania: study protocol for a randomized controlled trial
Authors:   NEOVITA Study Author Group, Bahl Rajiv , Bhandari Nita , Dube Brinda , Edmond Karen , Fawzi Wafaie , Fontaine Olivier , Kaur Jasmine , Kirkwood Betty R , Martines Jose , Masanja Honorati , Mazumder Sarmila , Msham Salum , Newton Sam , Oleary Maureen , Ruben Julia , Shannon Caitlin , Smith Emily , Taneja Sunita , Yoshida Sachiyo
Published: February 2012

Background

Vitamin A supplementation of 6-59 month old children is currently recommended by the World Health Organization based on evidence that it reduces mortality. There has been considerable interest in determining the benefits of neonatal vitamin A supplementation, but the results of existing trials are conflicting. A technical consultation convened by WHO pointed to the need for larger scale studies in Asia and Africa to inform global policy on the use of neonatal vitamin A supplementation. Three trials were therefore initiated in Ghana, India and Tanzania to determine if vitamin A supplementation (50,000 IU) given to neonates once orally on the day of birth or within the next two days will reduce mortality in the period from supplementation to 6 months of age compared to placebo.

Methods/Design

The trials are individually randomized, double masked, and placebo controlled. The required sample size is 40,200 in India and 32,000 each in Ghana and Tanzania. The study participants are neonates who fulfil age eligibility, whose families are likely to stay in the study area for the next 6 months, who are able to feed orally, and whose parent(s) provide informed written consent to participate in the study. Neonates randomized to the intervention group receive 50,000 IU vitamin A and the ones randomized to the control group receive placebo at the time of enrolment. Mortality and morbidity information are collected through periodic home visits by a study worker during infancy. The primary outcome of the study is mortality from supplementation to 6 months of age. The secondary outcome of the study is mortality from supplementation to 12 months of age. The three studies will be analysed independent of each other. Subgroup analysis will be carried out to determine the effect by birth weight, sex, and timing of DTP vaccine, socioeconomic groups and maternal large-dose vitamin A supplementation.

Discussion

The three ongoing studies are the largest studies evaluating the efficacy of vitamin A supplementation to neonates. Policy formulation will be based on the results of efficacy of the intervention from the ongoing randomized controlled trials combined with results of previous studies.

Trial Registration

Ghana: Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12610000582055
; India: CLINICALTRIALS.GOV - NCT01138449
; Tanzania: Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12610000636055.
The effect of low level laser on condylar growth during mandibular advancement in rabbits
Authors: Abtahi Mostafa , Poosti Maryam , Saghravanian Nasrollah , Sadeghi Kamran , Shafaee Hooman
Published: February 2012

Introduction

It has been shown that Low Level Laser (LLL) has a positive effect on bone formation. The aim of this study was to evaluate the effect of low level laser on condylar growth during mandibular advancement in rabbits.

Materials and methods

Continuous forward mandibular advancement was performed in fourteen male Albino rabbits with the mean age of 8 weeks and the mean weight of 1.5 ± 0.5 kg, with acrylic inclined planes. The rabbits were randomly assigned into two groups after 4 weeks. LLL (KLO3: wave length 630 nm) was irradiated at 3 points around the TMJ, through the skin in the first group. The exposure was performed for 3 minutes at each point (a total of 9 minutes) once a day for 3 weeks. The control group was not exposed to any irradiation. The rabbits in both groups were sacrificed after two months and the histological evaluation of TMJ was performed to compare fibrous tissue, cartilage, and new bone formation in condylar region in both groups. Disc displacement was also detected in both groups. Student's t-test, Exact Fisher and Chi square tests were used for the statistical analysis.

Results

The formation of fibrous tissue was significantly lower, while bone formation was significantly greater in lased group as compared with control group. The thickness of cartilage did not differ significantly between two groups.

Conclusion

Irradiation of LLL (KLO3) during mandibular advancement in rabbits, increases bone formation in condylar region, while neither increase in the cartilage thickness nor fibrous tissues was observed.
Increasing the sensitivity of controlled-source electromagnetics with synthetic aperture
Authors: Fan Y. , Snieder R. , Slob E. , Hunziker J. , Singer J. , Sheiman J. , Rosenquist M.
Published: February 2012

Controlled-source electromagnetics (CSEM) has been used as a derisking tool in the hydrocarbon exploration industry. We apply the concept of synthetic aperture to the low-frequency electromagnetic field in CSEM. Synthetic aperture sources have been used in radar imaging for many years. Using the synthetic aperture concept, big synthetic sources can be constructed by adding the response to small sources (building blocks) in different ways, and consequently, big sources with different radiation patterns can be created. We show that the detectability of hydrocarbons is significantly enhanced by applying synthetic aperture to CSEM data. More challenging targets such as deep reservoirs (4 km below sea floor) can be detected. The synthetic aperture technique also increases the sensitivity of the field to subsurface targets in the towing streamer acquisition. We also show that a pseudovertical source (orthogonally distributed dipole pairs) can be constructed synthetically, and that the detection capability of this pseudovertical source is increased by applying field steering. The synthetic aperture concept opens a new line of research in CSEM, with the freedom to design suitable synthetic aperture sources for a given purpose.
Polarity reversal correction for elastic reverse time migration
Authors: Du Qizhen , Zhu Yitong , Ba Jing
Published: February 2012

Polarity reversals in PS and SP images of elastic reverse time migration will cause destructive interference in the final stacked results, which may lead to an erroneous interpretation. We derive a polarity reversal correction based on an analysis of the polarity distribution of PS and SP images. The key aspect for a polarity reversal correction is the polarity distribution of the S-wave component. Polarity reversal correction methods can be performed according to the actual patterns of the polarity distribution in gathers. For the 2D isotropic case, a sign factor is introduced to represent the polarity distribution of the S-wave component; this sign factor can be computed using the energy flux density vector. We present a procedure to correct the polarity reversal for elastic reverse time migration in the common-shot domain. First, the sign factor is computed during the wavefield reconstruction for every imaging point. Then, the polarity reversal is corrected by multiplying the PS and SP images with the sign factor at every time step when an elastic imaging condition is applied. We also design a filter algorithm for the sign factor to improve its consistency along an event and thereby to diminish the impact of the inaccuracy of the energy flux density vector and to improve the imaging results. Numerical examples have shown that the polarity reversal correction procedure works and that the sign filter algorithm successfully eliminates the consequences of the inaccuracy of the energy flux density vector. The quality of the migration events is effectively improved.
miR-125 potentiates early neural specification of human embryonic stem cells
Authors: Boissart Claire , Nissan Xavier , Giraud-Triboult Karine , Peschanski Marc , Benchoua Alexandra
Published: February 2012

The role of microRNAs (miRNAs) as coordinators of stem cell fate has emerged over the last decade. We have used human embryonic stem cells to identify miRNAs involved in neural lineage commitment induced by the inhibition of TGFβ-like molecule-mediated pathways. Among several candidate miRNAs expressed in the fetal brain, the two isoforms of miR-125 alone were detected in a time window compatible with a role in neural commitment in vitro. Functional analysis indicated that miR-125 isoforms were actively involved in the promotion of pluripotent cell conversion into SOX1-positive neural precursors. miR-125 promotes neural conversion by avoiding the persistence of non-differentiated stem cells and repressing alternative fate choices. This was associated with the regulation by miR-125 of SMAD4, a key regulator of pluripotent stem cell lineage commitment. Activation of miR-125 was directly responsive to the levels of TGFβ-like molecules, placing miR-125 at the core of mechanisms that lead to the irreversible neural lineage commitment of pluripotent stem cells in response to external stimuli.
A zebrafish model of lethal congenital contracture syndrome 1 reveals Gle1 function in spinal neural precursor survival and motor axon arborization
Authors: Jao Li-En , Appel Bruce , Wente Susan R.
Published: February 2012

In humans, GLE1 is mutated in lethal congenital contracture syndrome 1 (LCCS1) leading to prenatal death of all affected fetuses. Although the molecular roles of Gle1 in nuclear mRNA export and translation have been documented, no animal models for this disease have been reported. To elucidate the function of Gle1 in vertebrate development, we used the zebrafish (Danio rerio) model system. gle1 mRNA is maternally deposited and widely expressed. Altering Gle1 using an insertional mutant or antisense morpholinos results in multiple defects, including immobility, small eyes, diminished pharyngeal arches, curved body axis, edema, underdeveloped intestine and cell death in the central nervous system. These phenotypes parallel those observed in LCCS1 human fetuses. Gle1 depletion also results in reduction of motoneurons and aberrant arborization of motor axons. Unexpectedly, the motoneuron deficiency results from apoptosis of neural precursors, not of differentiated motoneurons. Mosaic analyses further indicate that Gle1 activity is required extrinsically in the environment for normal motor axon arborization. Importantly, the zebrafish phenotypes caused by Gle1 deficiency are only rescued by expressing wild-type human GLE1 and not by the disease-linked FinMajor mutant form of GLE1. Together, our studies provide the first functional characterization of Gle1 in vertebrate development and reveal its essential role in actively dividing cells. We propose that defective GLE1 function in human LCCS1 results in both neurogenic and non-neurogenic defects linked to the apoptosis of proliferative organ precursors.
The fusion of early endosomes induces molecular motor-driven tubule formation and fission.
Authors: Skjeldal Frode M. , Strunze Sten , Bergeland Trygve , Walseng Even , FGregers Tone , Bakke Oddmund
Published: February 2012

Organelles in the endocytic pathway interact and communicate through the crucial mechanisms of fusion and fission. However, any specific link between fusion and fission has not yet been determined. To study the endosomal interactions with high spatial and temporal resolution, the endosomes were enlarged through two mechanistically different methods. Either expression of the MHC class II associated chaperone Invariant chain or Rab5 increased the fusion rate of early endosomes and resulted in enlarged endosomes. Fast homotypic fusions were studied, and immediately after the fusion a highly active and specific tubule formation and fission was observed. These explosive tubule formations following fusion seemed to be a direct effect of fusion. The tubule formations were dependent on microtubule interactions, and specifically controlled by Kif16b and dynein. Our results show that fusion of endosomes is a rapid process that destabilize the membrane and instantly induce molecular motor driven tubule formation and fission.
Acute depletion of plasma membrane Phosphatidylinositol 4,5-bisphosphate impairs specific steps in G protein-coupled receptor endocytosis
Authors: Tóth Dániel J. , Tóth József , Gulyás Gergő , Balla András , Balla Tamas , Hunyady László , Várnai Péter
Published: February 2012

Receptor endocytosis plays an important role in regulating the responsiveness of cells to specific ligands. Phosphatidylinositol 4,5-bisphosphate (PtdInsP2) has been shown to be critical for endocytosis of some cell surface receptors, such as EGF and transferrin receptor, but its role in G protein-coupled receptor internalization has not been investigated. By employing luciferase-labeled type 1 angiotensin II (AT1), type 2C serotonin (5HT2C) or β2 adrenergic (β2A) receptors and fluorescently tagged proteins (β-arrestin 2, plasma membrane targeted Venus, Rab5) we were able to follow the sequence of molecular interactions along the endocytic route of the receptors in HEK 293 cells using the highly sensitive method of bioluminescence resonance energy transfer and confocal microscopy. To study the role of plasma membrane PtdInsP2 in receptor endocytosis, we used our previously developed rapamycin-inducible heterodimerization system, in which the recruitment of a 5-phosphatase domain to the plasma membrane degrades PtdInsP2. Here we show that ligand-induced interaction of AT1, 5HT2C and β2A receptors with β-arrestin 2 was unaffected by PtdInsP2 depletion. However, arrival of the receptors to Rab5-positive early endosomes was completely abolished in the absence of PtdInsP2. Remarkably, removal of the receptors from the plasma membrane was reduced but not eliminated after PtdInsP2 depletion. Under these conditions, stimulated AT1 receptors clustered along the plasma membrane but did not enter the cells. Our data suggest that in the absence of PtdInsP2, these receptors move into clathrin-coated membrane structures, but these are not cleaved efficiently and hence cannot reach the early endosomal compartment.
Ligand oligomerization state controls Tie2 receptor trafficking and Angiopoietin-2 ligand-specific responses
Authors: Pietilä Riikka , Nätynki Marjut , Tammela Tuomas , Kangas Jaakko , Pulkki Kristina H. , Limaye Nisha , Vikkula Miikka , Koh Gou Young , Saharinen Pipsa , Alitalo Kari , Eklund Lauri
Published: February 2012

Angiopoietin 1 (Ang1) is an activating ligand for the endothelial receptor tyrosine kinase Tie2, whereas Ang2 acts as a context-dependent agonist or antagonist that has a destabilizing effect on the vasculature. The molecular mechanisms responsible for the versatile functions of Ang2 are poorly understood. We show here that Ang2, but not Ang1, induces Tie2 translocation to the specific cell-matrix contact sites located at the distal end of focal adhesions. The Ang2-specific Tie2 translocation was associated with distinct Tie2 activation and downstream signals which differed from those of Ang1, and lead to impaired cell motility and weak cell-matrix adhesion. We demonstrate that the different oligomeric/multimeric forms of the angiopoietins induce distinct patterns of Tie2 trafficking; the lower oligomerization state of native Ang2 was critical for the Ang2-specific Tie2 redistribution, while multimeric structures of Ang1 and Ang2 induced similar responses. The Ang2-specific Tie2 trafficking to cell-matrix contacts was also dependent on cell substratum, α2β1 integrin-containing cell-matrix adhesion sites and intact microtubules. Our data indicate that the different subcellular trafficking of Tie2/Ang2 and Tie2/Ang1 complexes generates ligand-specific responses in the angiopoietin-Tie signaling pathway, including modulation of cell-matrix interactions.
Deficiency of Porcupine, an O-acyltransferase gene, impairs convergent extension during gastrulation in zebrafish embryos and does not affect equivalently the trafficking of different Wnt proteins.
Authors: Chen Qiuhong , Takada Ritsuko , Takada Shinji
Published: February 2012

Porcupine (Porcn), an O-acyltransferase located in the endoplasmic reticulum (ER), is required for lipidation of Wnt proteins in mammalian culture cells, and Porcn-mediated lipidation is required for trafficking of Wnt proteins from the ER. However, it is still unclear whether Porcn is equivalently required for trafficking of all members of the Wnt family. In this study, we investigated the function of Porcn in zebrafish embryos. We identified two zebrafish homologs of porcupine, porcn and porcupine-like (porcn-l). Zebrafish porcn, but not porcn-l, restores secretion of Wnt proteins in porcn-deficient mouse L cells. Morpholino-mediated knockdown of porcn in zebrafish embryos impairs convergence and extension (CE) during gastrulation without changing embryonic patterning. Moreover, porcn interacts genetically with wnt5b and wnt11 in regulating CE. In contrast, porcn-deficient embryos do not exhibit phenotypes caused by failure in canonical Wnt signaling, which is activated by several Wnt ligands, including Wnt3a. Furthermore, expression of genes regulated by the canonical Wnt signaling pathway is not perturbed in knockdown embryos relative to that in the controls. While the trafficking and lipidation of ectopically expressed zebrafish Wnt5b and mouse Wnt5a are impaired in porcn-deficient embryos, those of ectopically expressed Wnt3a are less or no affected. In addition, the secretion of Wnt5a is inhibited by less amount of Porcn inhibitor than that of Wnt3a in HEK293T cells. Thus, decrease of Porcn activity does not equivalently affect trafficking and lipidation of different Wnt proteins in zebrafish embryos and in mammalian culture cells.
Mucolipin controls lysosome exocytosis in Dictyostelium
Authors: Lima Wanessa C. , Leuba Florence , Soldati Thierry , Cosson Pierre
Published: February 2012

Mucolipidosis type IV is a still poorly understood lysosomal storage disease caused by alterations in the mucolipin lysosomal calcium channel. In this study, we generated mucolipin knockout Dictyostelium cells, and observed that lysosome exocytosis was markedly increased in these cells compared to wild-type cells. In addition, mucolipin KO cells were more resistant to calcium deprivation, and the calcium concentration in their secretory lysosomes was decreased, suggesting that mucolipin transfers calcium ions from the cytosol to the lumen of secretory lysosomes. We speculate that mucolipin attenuates the fusogenic effect of local cytosolic calcium increases by dissipating them into the lumen of lysosomal compartments.
Wnt3a-stimulated LRP6 phosphorylation is dependent upon arginine methylation of G3BP2
Authors: Bikkavilli Rama Kamesh , Malbon Craig C.
Published: February 2012

Wnt signaling is initiated upon binding of Wnts to Frizzleds and their co-receptors LRP5/6. The signal is then propagated to several downstream effectors, mediated by the phosphoprotein scaffold, Dishevelled. We report a novel role for arginine methylation in regulating Wnt3a-stimulated LRP6 phosphorylation. G3BP2, a Dishevelled-associated protein, is methylated in response to Wnt3a. The Wnt3a-induced LRP6 phosphorylation is attenuated by G3BP2 knock-down, chemical inhibition of methyl transferase activity, or expression of methylation-deficient mutants of G3BP2. Arginine methylation of G3BP2 appears to be a Wnt3a-sensitive “switch” regulating LRP6 phosphorylation and canonical Wnt/β-catenin signaling.
Heterodimerization of serotonin receptors 5-HT1A and 5-HT7 differentially regulates receptor signalling and trafficking
Authors: Renner Ute , Zeug Andre , Woehler Andrew , Niebert Markus , Dityatev Alexander , Dityateva Galina , Gorinski Nataliya , Guseva Daria , Abdel-Galil Dalia , Fröhlich Matthias , Döring Frank , Wischmeyer Erhard , Richter Diethelm W. , Neher Erwin , Ponimaskin Evgeni G.
Published: February 2012

Serotonin receptors 5-HT1A and 5-HT7 are highly co-expressed in brain regions implicated in depression. However, their functional interaction has not been established. In the present study we show that 5-HT1A and 5-HT7 receptors form heterodimers both in vitro and in vivo. Foerster resonance energy transfer-based assays revealed that, in addition to heterodimers, homodimers composed either by 5-HT1A or 5-HT7 receptors together with monomers co-exist in cells. The highest affinity to form the complex was obtained for the 5-HT7-5-HT7 homodimers, followed by the 5-HT7-5-HT1A heterodimers and 5-HT1A-5-HT1A homodimers. Functionally, heterodimerization decreases 5-HT1A receptor-mediated activation of Gi-protein without affecting 5-HT7 receptor-mediated signalling. Moreover, heterodimerization markedly decreases the ability of the 5-HT1A receptor to activate G-protein gated inwardly rectifying potassium channels in a heterologous system. The inhibitory effect on such channels was also preserved in hippocampal neurons, demonstrating a physiological relevance of heteromerization in vivo. In addition, heterodimerization is critically involved in initiation of the serotonin-mediated 5-HT1A receptor internalization and also enhances the ability of the 5-HT1A receptor to activate the mitogen-activated protein kinases. Finally, we found that production of 5-HT7 receptors in hippocampus continuously decreases during postnatal development, indicating that the relative concentration of 5-HT1A-5-HT7 heterodimers and, consequently, their functional importance undergoes pronounced developmental changes.
Molecular mechanism of interactions of the physiological anti-hypertensive peptide catestatin with the neuronal nicotinic acetylcholine receptor
Authors: Sahu Bhavani S. , Mohan Jagan , Sahu Giriraj , Singh Pradeep K. , Sonawane Parshuram J. , Sasi Binu K. , Allu Prasanna K. R. , Maji Samir K. , Bera Amal K. , Senapati Sanjib , Mahapatra Nitish R.
Published: February 2012

Catestatin (CST), a chromogranin A-derived peptide, is a potent endogenous inhibitor of the neuronal nicotinic acetylcholine receptor (nAChR). It exerts anti-hypertensive effect by acting as a “physiological brake” on transmitter release into the circulation. However, the mechanism of interaction of CST with nAChR is only partially understood. To unravel molecular interactions of the common/wild type human CST (CST-WT) as well as its naturally-occurring variants (viz. CST-364S and CST-370L having Gly→Ser and Pro→Leu substitutions, respectively) with the human α3β4 nAChR we generated a homology-modeled human α3β4 nAChR structure and solution structures of CST peptides. Docking and molecular dynamics simulations showed that ∼90% of interacting residues were within the N-terminal 15-residues of CST peptides. The rank order of binding affinity of these peptides with nAChR was: CST-370L>CST-WT>CST-364S; the extent of occlusion of the receptor pore by these peptides was also in the same order. In corroboration with computational predictions, circular dichroism analysis revealed significant differences in global structures of CST peptides (e.g., the order of alpha-helical content was: CST-370L>CST-WT>CST-364S). Consistently, CST peptides blocked various stages of nAChR signal transduction (viz. nicotine/acetylcholine-evoked inward current, intracellular-calcium rise, catecholamine secretion in/from neuron-differentiated PC12 cells) in the same rank order. Taken together, this study showed molecular interactions between human CST peptides and human α3β4 nAChR, and demonstrated that alterations in the CST secondary structure led to the gain of potency for CST-370L and loss of potency for CST-364S. These novel findings have implications for understanding the nicotinic cholinergic signaling in humans.
Creation of Functional and Structured Polymer Particles by Self-Organized Precipitation (SORP)
Authors: Yabu Hiroshi
Published: February 2012

In this account, we review recent developments in the preparation of various functional and nanostructured polymer particles by precipitation-based methods. First, we present an overview of recent polymer particle preparation methods including methods for precipitation-based particle preparation. Next, we introduce the self-organized precipitation and its advantages. We discuss the morphological control of polymer particles based on the types of polymer materials used for particle preparation. We also introduce the preparation of organic–inorganic composite particles. Finally, we discuss the future outlook of nanostructured polymer particles.
Sports behaviour among HIV-infected versus non-infected individuals in a Berlin cohort
Authors: Stein L , Hechler D , Jessen A B , Neumann K , Jessen H , Beneke R
Published: February 2012

Physical activity has been recommended based on beneficial effects described in HIV-infected patients. However, such guidelines do not take into account actual sport behaviours and general attitudes towards physical activity. To evaluate actual sport activity and attitudes towards sport in HIV-infected versus non-infected individuals we conducted an anonymous questionnaire investigating the prevalence, as well as possible changes, in sports engagement and the overall attitude to physical activity. A total of 283 patients of a general care facility specialized in the treatment of HIV/AIDS in Berlin, Germany, participated; 124 were HIV infected and 159 were non-infected, mostly men who have sex with men (MSM) (88%), with a median age of 35 years. The HIV-infected participants had a median CD4+ count of 554 cells/µL and 48.8% of them were using antiretroviral therapy (ART) at the time of survey. The proportion of patients actually performing physical activity was significantly lower ( P = 0.028) within the HIV-infected group (61.3%) than within the non-infected group (74.2%). This difference remained significant after accounting for possible confounders such as age, gender, injecting drug use and sexual preferences. Previously reported sport activity prevalence was similar in both groups on leaving school. From our data we could not identify an association between the time of HIV diagnosis and changes in sports activity. In conclusion, fewer HIV-infected individuals report physical activity than non-infected individuals. Sociodemographic studies to evaluate potential differences in sports behaviour are required in order to inform exercise guidelines for HIV-infected patients.
Cervical cytological abnormalities and factors associated with high-grade squamous intraepithelial lesions among HIV-infected women from Rio de Janeiro, Brazil
Authors: Luz P M , Velasque L , Friedman R K , Russomano F , Andrade A C , Moreira R I , Chicarino-Coelho J , Pires E , Veloso V G , Grinsztejn B
Published: February 2012

Although cervical cancer remains a major public health problem in Brazil, knowledge of cervical cytological abnormalities among HIV-infected women remains scarce. At baseline evaluation of a cohort followed in Rio de Janeiro, Brazil, 703 HIV-infected women underwent cytology-based cervical cancer screening and human papillomavirus (HPV) DNA testing. Poisson regression analysis was used to evaluate the association of factors with the presence of high-grade squamous intraepithelial lesions (HSIL). Cervical cytology was abnormal in 24.3% of the women; 4.1% had HSIL. Beyond HPV infection, factors independently associated with the presence of HSIL was age (≥25 and ≤40 years, prevalence ratio [PR] 2.60, 95% confidence interval [CI] 1.11–6.10), and more than three pregnancies was protective (PR 0.33, 95% CI 0.11–0.94). High coverage of cervical cancer screening is warranted to prevent morbidity and mortality from cervical cancer in this population.
Factors associated with viral load suppression in HIV-infected pregnant women in Rio de Janeiro, Brazil
Authors: Joao E C , Gouvêa M I , Menezes J A , Sidi L C , Cruz M L S , Berardo P T , Ceci L , Cardoso C A , Teixeira M de L B , Calvet G A , Matos H J
Published: February 2012

Viral load (VL) near delivery is a determinant of mother-to-child transmission (MTCT) of HIV. To evaluate factors associated with an undetectable VL near delivery in HIV-infected pregnant women receiving highly active antiretroviral therapy (HAART) and non-HAART regimens, HIV-infected pregnant women with a detectable VL at entry and having used antiretrovirals for ≥4 weeks before delivery were selected. Multivariate analysis was employed using binary logistic unconditional models; the dependent variable was having a VL <400 copies/mL near delivery. VL suppression was achieved in 403/707 women (57%): 65.4% in the HAART group, but only 26% in the non-HAART group P = 0.001. Duration of HAART was correlated with VL suppression, with maximum benefit seen after ≥12 weeks of therapy (odds ratio [OR]: 2.51; 95% confidence interval [CI]: 1.72–3.65). CD4+ cell count near delivery (OR: 1.53; 95% CI: 1.06–2.20) and baseline VL (OR: 0.74; 95% CI: 0.58–0.94) were also independently associated with VL suppression. Overall MTCT rate was 1.6%. HAART for ≥12 weeks, baseline VL and CD4 cell count near delivery were independently associated with viral suppression near delivery.