bluuebunny/crossref_metadata_2025 huggingface dataset:
Reticulate evolution: frequent introgressive hybridization among chinese hares (genus lepus) revealed by analyses of multiple mitochondrial and nuclear DNA loci
Authors: Liu Jiang , Yu Li , Arnold Michael L , Wu Chun-Hua , Wu Shi-Fang , Lu Xin , Zhang Ya-Ping
Published: July 2011

Background

Interspecific hybridization may lead to the introgression of genes and genomes across species barriers and contribute to a reticulate evolutionary pattern and thus taxonomic uncertainties. Since several previous studies have demonstrated that introgressive hybridization has occurred among some species withinLepus, therefore it is possible that introgressive hybridization events also occur among ChineseLepusspecies and contribute to the current taxonomic confusion.

Results

Data from four mtDNA genes, from 116 individuals, and one nuclear gene, from 119 individuals, provides the first evidence of frequent introgression events via historical and recent interspecific hybridizations among six ChineseLepusspecies. Remarkably, the mtDNA ofL. mandshuricuswas completely replaced by mtDNA fromL. timidusandL. sinensis. Analysis of the nuclear DNA sequence revealed a high proportion of heterozygous genotypes containing alleles from two divergent clades and that several haplotypes were shared among species, suggesting repeated and recent introgression. Furthermore, results from the present analyses suggest that Chinese hares belong to eight species.

Conclusion

This study provides a framework for understanding the patterns of speciation and the taxonomy of this clade. The existence of morphological intermediates and atypical mitochondrial gene genealogies resulting from frequent hybridization events likely contribute to the current taxonomic confusion of Chinese hares. The present study also demonstrated that nuclear gene sequence could offer a powerful complementary data set with mtDNA in tracing a complete evolutionary history of recently diverged species.
QTLRel: an R Package for Genome-wide Association Studies in which Relatedness is a Concern
Authors: Cheng Riyan , Abney Mark , Palmer Abraham A , Skol Andrew D
Published: July 2011

Background

Existing software for quantitative trait mapping is either not able to model polygenic variation or does not allow incorporation of more than one genetic variance component. Improperly modeling the genetic relatedness among subjects can result in excessive false positives. We have developed an R package, QTLRel, to enable more flexible modeling of genetic relatedness as well as covariates and non-genetic variance components.

Results

We have successfully used the package to analyze many datasets, including F34 body weight data that contains 688 individuals genotyped at 3105 SNP markers and identified 11 QTL. It took 295 seconds to estimate variance components and 70 seconds to perform the genome scan on an Linux machine equipped with a 2.40GHz Intel(R) Core(TM)2 Quad CPU.

Conclusions

QTLRel provides a toolkit for genome-wide association studies that is capable of calculating genetic incidence matrices from pedigrees, estimating variance components, performing genome scans, incorporating interactive covariates and genetic and non-genetic variance components, as well as other functionalities such as multiple-QTL mapping and genome-wide epistasis.
Detection of segregation distortion loci in triticale (x Triticosecale Wittmack) based on a high-density DArT marker consensus genetic linkage map
Authors: Alheit Katharina V , Reif Jochen C , Maurer Hans Peter , Hahn Volker , Weissmann Elmar A , Miedaner Thomas , Würschum Tobias
Published: July 2011

Background

Triticale is adapted to a wide range of abiotic stress conditions, is an important high-quality feed stock and produces similar grain yield but more biomass compared to other crops. Modern genomic approaches aimed at enhancing breeding progress in cereals require high-quality genetic linkage maps. Consensus maps are genetic maps that are created by a joint analysis of the data from several segregating populations and different approaches are available for their construction. The phenomenon that alleles at a locus deviate from the Mendelian expectation has been defined as segregation distortion. The study of segregation distortion is of particular interest in doubled haploid (DH) populations due to the selection pressure exerted on the plants during the process of their establishment.

Results

The final consensus map, constructed out of six segregating populations derived from nine parental lines, incorporated 2555 DArT markers mapped to 2602 loci (1929 unique). The map spanned 2309.9 cM with an average number of 123.9 loci per chromosome and an average marker density of one unique locus every 1.2 cM. The R genome showed the highest marker coverage followed by the B genome and the A genome. In general, locus order was well maintained between the consensus linkage map and the component maps. However, we observed several groups of loci for which the colinearity was slightly uneven. Among the 2602 loci mapped on the consensus map, 886 showed distorted segregation in at least one of the individual mapping populations. In several DH populations derived by androgenesis, we found chromosomes (2B, 3B, 1R, 2R, 4R and 7R) containing regions where markers exhibited a distorted segregation pattern. In addition, we observed evidence for segregation distortion between pairs of loci caused either by a predominance of parental or recombinant genotypes.

Conclusions

We have constructed a reliable, high-density DArT marker consensus genetic linkage map as a basis for genomic approaches in triticale research and breeding, for example for multiple-line cross QTL mapping experiments. The results of our study exemplify the tremendous impact of different DH production techniques on allele frequencies and segregation distortion covering whole chromosomes.
Validation of the Turkish version of the Centre for Epidemiologic Studies Depression Scale (CES-D) in patients with Type 2 diabetes mellitus
Authors: Lehmann Vicky , Makine Ceylan , Karşıdağ Çagatay , Kadıoğlu Pinar , Karşıdağ Kubilay , Pouwer François
Published: July 2011

Background

Depression is a common co-morbid health problem in patients with diabetes that is underrecognised. Current international guidelines recommend screening for depression in patients with diabetes. Yet, few depression screening instruments have been validated for use in this particular group of patients. Aim of the present study was to investigate the psychometric properties of the Turkish version of the Centre for Epidemiologic Studies Depression Scale (CES-D) in patients with type 2 diabetes.

Methods

A sample of 151 Turkish outpatients with type 2 diabetes completed the CES-D, the World Health Organization-Five Well-Being Index (WHO-5), and the Problem Areas in Diabetes scale (PAID). Explanatory factor analyses, various correlations and Cronbach's alpha were investigated to test the validity and reliability of the CES-D in Turkish diabetes outpatients.

Results

The original four-factor structure proposed by Radloff was not confirmed. Explanatory factor analyses revealed a two-factor structure representing two subscales: (1) depressed mood combined with somatic symptoms of depression and (2) positive affect. However, one item showed insufficient factor loadings. Cronbach's alpha of the total score was high (0.88), as were split-half coefficients (0.77-0.90). The correlation of the CES-D with the WHO-5 was the strongest (r = -0.70), and supported concurrent validity.

Conclusion

The CES-D appears to be a valid measure for the assessment of depression in Turkish diabetes patients. Future studies should investigate its sensitivity and specificity as well as test-retest reliability.
Upper limb children action-observation training (UP-CAT): a randomised controlled trial in Hemiplegic Cerebral Palsy
Authors: Sgandurra Giuseppina , Ferrari Adriano , Cossu Giuseppe , Guzzetta Andrea , Biagi Laura , Tosetti Michela , Fogassi Leonardo , Cioni Giovanni
Published: July 2011

Background

Rehabilitation for children with hemiplegic cerebral palsy (HCP) aimed to improve function of the impaired upper limb (UL) uses a wide range of intervention programs. A new rehabilitative approach, called Action-Observation Therapy, based on the recent discovery of mirror neurons, has been used in adult stroke but not in children. The purpose of the present study is to design a randomised controlled trial (RCT) for evaluating the efficacy of Action-Observation Therapy in improving UL activity in children with HCP.

Methods/Design

The trial is designed according to CONSORT Statement. It is a randomised, evaluator-blinded, match-pair group trial. Children with HCP will be randomised within pairs to either experimental or control group. The experimental group will perform an Action-Observation Therapy, called UP-CAT (Upper Limb-Children Action-Observation Training) in which they will watch video sequences showing goal-directed actions, chosen according to children UL functional level, combined with motor training with their hemiplegic UL. The control group will perform the same tailored actions after watching computer games. A careful revision of psychometric properties of UL outcome measures for children with hemiplegia was performed. Assisting Hand Assessment was chosen as primary measure and, based on its calculation power, a sample size of 12 matched pairs was established. Moreover, Melbourne and ABILHAND-Kids were included as secondary measures. The time line of assessments will be T0 (in the week preceding the onset of the treatment), T1 and T2 (in the week after the end of the treatment and 8 weeks later, respectively). A further assessment will be performed at T3 (24 weeks after T1), to evaluate the retention of effects. In a subgroup of children enrolled in both groups functional Magnetic Resonance Imaging, exploring the mirror system and sensory-motor function, will be performed at T0, T1 and T2.

Discussion

The paper aims to describe the methodology of a RCT for evaluating the efficacy of Action-Observation Therapy in improving UL activity in children with hemiplegia. This study will be the first to test this new type of treatment in childhood. The paper presents the theoretical background, study hypotheses, outcome measures and trial methodology.

Trial Registration

NCT01016496
The association between failed quit attempts and increased levels of psychological distress in smokers in a large New Zealand cohort
Authors: van der Deen Frederieke S , Carter Kristie N , Wilson Nick , Collings Sunny
Published: July 2011

Background

Although the association between smoking status and poorer mental health has been well documented, the association between quit status and psychological distress is less clear. The aim of the present study is to investigate the association of smoking status and quit status with psychological distress.

Methods

Data for this study is from a single year of the Survey of Families, Income and Employment (SoFIE) conducted in New Zealand (2004/05) (n = 18,525 respondents). Smoking status and quit status were treated as exposure variables, and psychological distress (Kessler-10) was treated as the outcome variable. Logistic regression analyses were performed to determine the association of smoking with psychological distress in the whole adult population and quit status with psychological distress in the ex- and current-smoking population.

Results

Current smokers had higher rates of high and very high psychological distress compared to never smokers (adjusted odds ratio (aOR) = 1.45; 95% CI: 1.24-1.69). Unsuccessful quitters had much higher levels of high to very high levels of psychological distress (16%) than any other group. Moreover, compared to long-term ex-smokers, unsuccessful quitters had a much higher odds of high to very high levels of psychological distress (aOR = 1.73; 95% CI: 1.36-2.21).

Conclusion

These findings suggest that the significant association between smoking and psychological distress might be partly explained by increased levels of psychological distress among current smokers who made a quit attempt in the last year. This issue needs further study as it has implications for optimising the design of quitting support.
Pre-ejection period by radial artery tonometry supplements echo doppler findings during biventricular pacemaker optimization
Authors: Taha Nima , Zhang Jing , Rafie Reza , Ranjan Rupesh , Qamruddin Salima , Naqvi Tasneem Z
Published: July 2011

Background

Biventricular (Biv) pacemaker echo optimization has been shown to improve cardiac output however is not routinely used due to its complexity. We investigated the role of a simple method involving computerized pre-ejection time (PEP) assessment by radial artery tonometry in guiding Biv pacemaker optimization.

Methods

Blinded echo and radial artery tonometry were performed simultaneously in 37 patients, age 69.1 ± 12.8 years, left ventricular (LV) ejection fraction (EF) 33 ± 10%, during Biv pacemaker optimization. Effect of optimization on echo derived velocity time integral (VTI), ejection time (ET), myocardial performance index (MPI), radial artery tonometry derived PEP and echo-radial artery tonometry derived PEP/VTI and PEP/ET indices was evaluated.

Results

Significant improvement post optimization was achieved in LV ET (286.9 ± 37.3 to 299 ± 34.6 ms, p < 0.001), LV VTI (15.9 ± 4.8 cm to 18.4 ± 5.1 cm, p < 0.001) and MPI (0.57 ± 0.2 to 0.45 ± 0.13, p < 0.001) and in PEP (246.7 ± 36.1 ms to 234.7 ± 35.5 ms, p = 0.003), PEP/ET (0.88 ± 0.21 to 0.79 ± 0.17, p < 0.001), and PEP/VTI (17.3 ± 7 to 13.78 ± 4.7, p < 0.001). The correlation between comprehensive echo Doppler and radial artery tonometry-PEP guided optimal atrioventricular delay (AVD) and optimal interventricular delay (VVD) was 0.75 (p < 0.001) and 0.69 (p < 0.001) respectively. In 29 patients with follow up assessment, New York Heart Association (NYHA) class reduced from 2.5 ± 0.8 to 2.0 ± 0.9 (p = 0.004) at 1.8 ± 1.4 months.

Conclusion

An acute shortening of PEP by radial artery tonometry occurs post Biv pacemaker optimization and correlates with improvement in hemodynamics by echo Doppler and may provide a cost-efficient approach to assist with Biv pacemaker echo optimization.
Controlling liver cancer internationally: A qualitative study of clinicians' perceptions of current public policy needs
Authors: Bridges John FP , Gallego Gisselle , Blauvelt Barri M
Published: July 2011

Background

Liver cancer is the fifth most common cancer in men and the seventh for women. Usually because of late diagnosis, the prognosis for liver cancer remains poor, resulting in liver cancer being the third most common cause of death from cancer. While some countries have treatment guidelines, little is known or understood about the strategies needed for liver cancer control internationally.

Objective

To explore leading liver cancer clinician's perceptions of the current public policy needs to control liver cancer internationally.

Methods

Key informant interviews were conducted with a range of liver cancer clinicians involved in policy in eleven countries. Interviews were digitally recorded, transcribed verbatim, translated (where necessary), de-identified and analyzed by two researchers using a constant comparative method.

Results

Twenty in-depth semi-structured interviews were conducted in: Australia, China, France, Germany, Italy, Japan, Spain, South Korea, Taiwan, Turkey and the United States. Nine themes were identified and cluster into three groups: 1) Promoting prevention via early risk assessment, focusing on viral hepatitis and other lifestyle factors; 2) Increasing political, public and medical community awareness; and 3) Improving funding for screening, liver cancer surveillance and treatment.

Conclusion

This study is an important step towards developing an evidence-based approach to assessing preparedness for implementing comprehensive liver cancer control strategies. Evaluation mechanisms to assess countries' performance on the needs described are needed. Future research will concentrate of understanding how these needs vary across countries and the optimal strategies to improve the diagnosis and prognosis of patients with liver cancer internationally.
Liver mitochondrial dysfunction is reverted by insulin-like growth factor II (IGF-II) in aging rats
Authors: Garcia-Fernandez Maria , Sierra Inma , Puche Juan E , Guerra Lucia , Castilla-Cortazar Inma
Published: July 2011

Background

Serum IGF-I and IGF-II levels decline with age. IGF-I replacement therapy reduces the impact of age in rats. We have recently reported that IGF-II is able to act, in part, as an analogous of IGF-I in aging rats reducing oxidative damage in brain and liver associated with a normalization of antioxidant enzyme activities. Since mitochondria seem to be the most important cellular target of IGF-I, the aim of this work was to investigate whether the cytoprotective actions of IGF-II therapy are mediated by mitochondrial protection.

Methods

Three groups of rats were included in the experimental protocol young controls (17 weeks old); untreated old rats (103 weeks old); and aging rats (103 weeks old) treated with IGF-II (2 μg/100 g body weight and day) for 30 days.

Results

Compared with young controls, untreated old rats showed an increase of oxidative damage in isolated mitochondria with a dysfunction characterized by: reduction of mitochondrial membrane potential (MMP) and ATP synthesis and increase of intramitochondrial free radicals production and proton leak rates. In addition, in untreated old rats mitochondrial respiration was not blocked by atractyloside. In accordance, old rats showed an overexpression of the active fragment of caspases 3 and 9 in liver homogenates. IGF-II therapy corrected all of these parameters of mitochondrial dysfunction and reduced activation of caspases.

Conclusions

The cytoprotective effects of IGF-II are related to mitochondrial protection leading to increased ATP production reducing free radical generation, oxidative damage and apoptosis.
High-efficiency dye-sensitized solar cells based on robust and both-end-open TiO2 nanotube membranes
Authors: Lin Jia , Chen Jingfei , Chen Xianfeng
Published: July 2011

In the present work, dye-sensitized solar cells (DSSCs) were fabricated by incorporating transparent electrodes of ordered free-standing TiO2 nanotube (TNT) arrays with both ends open transferred onto fluorine-doped tin oxide (FTO) conductive glass. The high-quality TiO2 membranes used here were obtained by a self-detaching technique, with the superiorities of facile but reliable procedures. Afterwards, these TNT membranes can be easily transferred to FTO glass substrates by TiO2 nanoparticle paste without any crack. Compared with those DSSCs consisting of the bottom-closed membranes or attached to Ti substrate, the carefully assembled and front-side illuminated DSSCs showed an enhanced solar energy conversion efficiency as high as 5.32% of 24-μm-thick TiO2 nanotube membranes without further treatments. These results reveal that by facilitating high-quality membrane synthesis, this kind of DSSCs assembly with optimized tube configuration can have a fascinating future.
An OFDMA resource allocation algorithm based on coalitional games
Authors: Shams Farshad , Bacci Giacomo , Luise Marco
Published: July 2011

This work investigates a fair adaptive resource management criterion (in terms of transmit powers and subchannel assignment) for the uplink of an orthogonal frequency-division multiple access network, populated by mobile users with constraints in terms of target data rates. The inherent optimization problem is tackled with the analytical tools of coalitional game theory, and a practical algorithm based on Markov modeling is introduced. The proposed scheme allows the mobile devices to fulfill their rate demands exactly with a minimum utilization of network resources. Simulation results show that the average number of operations of the proposed iterative algorithm are much lower than K · N, where N and K are the number of allocated subcarriers and of mobile terminals.
An extragradient-like approximation method for variational inequalities and fixed point problems
Authors: Ceng Lu-Chuan , Ansari Qamrul Hasan , Wong Ngai-Ching , Yao Jen-Chih
Published: July 2011

The purpose of this paper is to investigate the problem of finding a common element of the set of fixed points of an asymptotically strict pseudocontractive mapping in the intermediate sense and the set of solutions of a variational inequality problem for a monotone and Lipschitz continuous mapping. We introduce an extragradient-like iterative algorithm that is based on the extragradient-like approximation method and the modified Mann iteration process. We establish a strong convergence theorem for two sequences generated by this extragradient-like iterative algorithm. Utilizing this theorem, we also design an iterative process for finding a common fixed point of two mappings, one of which is an asymptotically strict pseudocontractive mapping in the intermediate sense and the other taken from the more general class of Lipschitz pseudocontractive mappings.

1991 MSC: 47H09; 47J20.
Herpes simplex virus type 1 UL14 tegument protein regulates intracellular compartmentalization of major tegument protein VP16
Authors: Ohta Akane , Yamauchi Yohei , Muto Yoshifumi , Kimura Hiroshi , Nishiyama Yukihiro
Published: July 2011

Background

Herpes simplex virus type 1 (HSV-1) has a complicated life-cycle, and its genome encodes many components that can modify the cellular environment to facilitate efficient viral replication. The protein UL14 is likely involved in viral maturation and egress (Cunningham C. et al), and it facilitates the nuclear translocation of viral capsids and the tegument protein VP16 during the immediate-early phase of infection (Yamauchi Y. et al, 2008). UL14 of herpes simplex virus type 2 exhibits multiple functions (Yamauchi Y. et al, 2001, 2002, 2003).

Methods

To better understand the function(s) of UL14, we generated VP16-GFP-incorporated UL14-mutant viruses with either single (K51M) or triple (R60A, R64A, E68D) amino acid substitutions in the heat shock protein (HSP)-like sequence of UL14. We observed the morphology of cells infected with UL14-null virus and amino acid-substituted UL14-mutant viruses at different time points after infection.

Results

UL14(3P)-VP16GFP and UL14D-VP16GFP (UL14-null) viruses caused similar defects with respect to growth kinetics, compartmentalization of tegument proteins, and cellular morphology in the late phase. Both the UL14D-VP16GFP and UL14(3P)-VP16GFP viruses led to the formation of an aggresome that incorporated some tegument proteins but did not include nuclear-egressed viral capsids.

Conclusions

Our findings suggest that a cluster of charged residues within the HSP-like sequence of UL14 is important for the molecular chaperone-like functions of UL14, and this activity is required for the acquisition of functionality of VP16 and UL46. In addition, UL14 likely contributes to maintaining cellular homeostasis following infection, including cytoskeletal organization. However, direct interactions between UL14 and VP16, UL46, or other cellular or viral proteins remain unclear.
Streptozotocin-Induced Early Thermal Hyperalgesia is Independent of Glycemic State of Rats: Role of Transient Receptor Potential Vanilloid 1(TRPV1) and Inflammatory Mediators
Authors: Bishnoi Mahendra , Bosgraaf Christine A , Abooj uvil , Zhong Linlin , Premkumar Louis S
Published: July 2011

Background:

Streptozotocin (STZ) is used as a common tool to induce diabetes and to study diabetes-induced complications including diabetic peripheral neuropathy (DPN). Previously, we have reported that STZ induces a direct effect on neurons through expression and function of the Transient receptor potential vanilloid 1 (TRPV1) channel in sensory neurons resulting in thermal hyperalgesia, even in non-diabetic STZ-treated mice. In the present study, we investigated the role of expression and function of TRPV1 in the central sensory nerve terminals in the spinal cord in STZ-induced hyperalgesia in rats.

Results:

We found that a proportion of STZ-treated rats were normoglycemic but still exhibited thermal hyperalgesia and mechanical allodynia. Immunohistochemical data show that STZ treatment, irrespective of glycemic state of the animal, caused microglial activation and increased expression of TRPV1 in spinal dorsal horn. Further, there was a significant increase in the levels of pro-inflammatory mediators (IL-1β, IL-6 and TNF-α) in spinal cord tissue, irrespective of the glycemic state. Capsaicin-stimulated release of calcitonin gene related peptide (CGRP) was significantly higher in the spinal cord of STZ-treated animals. Intrathecal administration of resiniferatoxin (RTX), a potent TRPV1 agonist, significantly attenuated STZ-induced thermal hyperalgesia, but not mechanical allodynia. RTX treatment also prevented the increase in TRPV1-mediated neuropeptide release in the spinal cord tissue.

Conclusions:

From these results, it is concluded that TRPV1 is an integral component of initiating and maintaining inflammatory thermal hyperalgesia, which can be alleviated by intrathecal administration of RTX. Further, the results suggest that enhanced expression and inflammation-induced sensitization of TRPV1 at the spinal cord may play a role in central sensitization in STZ-induced neuropathy.
Highly Localized Interactions between Sensory Neurons and Sprouting Sympathetic Fibers Observed in a Transgenic Tyrosine Hydroxylase Reporter Mouse
Authors: Xie Wenrui , Strong Judith A , Mao Juxian , Zhang Jun-Ming
Published: July 2011

Background:

Sprouting of sympathetic fibers into sensory ganglia occurs in many preclinical pain models, providing a possible anatomical substrate for sympathetically enhanced pain. However, the functional consequences of this sprouting have been controversial. We used a transgenic mouse in which sympathetic fibers expressed green fluorescent protein, observable in live tissue. Medium and large diameter lumbar sensory neurons with and without nearby sympathetic fibers were recorded in whole ganglion preparations using microelectrodes.

Results:

After spinal nerve ligation, sympathetic sprouting was extensive by 3 days. Abnormal spontaneous activity increased to 15% and rheobase was reduced. Spontaneously active cells had Aαβ conduction velocities but were clustered near the medium/large cell boundary. Neurons with sympathetic basket formations had a dramatically higher incidence of spontaneous activity (71%) and had lower rheobase than cells with no sympathetic fibers nearby. Cells with lower density nearby fibers had intermediate phenotypes. Immunohistochemistry of sectioned ganglia showed that cells surrounded by sympathetic fibers were enriched in nociceptive markers TrkA, substance P, or CGRP. Spontaneous activity began before sympathetic sprouting was observed, but blocking sympathetic sprouting on day 3 by cutting the dorsal ramus in addition to the ventral ramus of the spinal nerve greatly reduced abnormal spontaneous activity.

Conclusions:

The data suggest that early sympathetic sprouting into the sensory ganglia may have highly localized, excitatory effects. Quantitatively, neurons with sympathetic basket formations may account for more than half of the observed spontaneous activity, despite being relatively rare. Spontaneous activity in sensory neurons and sympathetic sprouting may be mutually re-enforcing.
Differential trafficking of AMPA receptors following activation of NMDA receptors and mGluRs
Authors: Sanderson Thomas M , Collingridge Graham L , Fitzjohn Stephen M
Published: July 2011

The removal of AMPA receptors from synapses is a major component of long-term depression (LTD). How this occurs, however, is still only partially understood. To investigate the trafficking of AMPA receptors in real-time we previously tagged the GluA2 subunit of AMPA receptors with ecliptic pHluorin and studied the effects of NMDA receptor activation. In the present study we have compared the effect of NMDA receptor and group I mGluR activation, using GluA2 tagged with super ecliptic pHluorin (SEP-GluA2) expressed in cultured hippocampal neurons. Surprisingly, agonists of the two receptors, which are both able to induce chemical forms of LTD, had clearly distinct effects on AMPA receptor trafficking. In agreement with our previous work we found that transient NMDA receptor activation results in an initial decrease in surface GluA2 from extrasynaptic sites followed by a delayed reduction in GluA2 from puncta (putative synapses). In contrast, transient activation of group I mGluRs, using DHPG, led to a pronounced but more delayed decrease in GluA2 from the dendritic shafts. Surprisingly, there was no average change in the fluorescence of the puncta. Examination of fluorescence at individual puncta, however, indicated that alterations did take place, with some puncta showing an increase and others a decrease in fluorescence. The effects of DHPG were, like DHPG-induced LTD, prevented by treatment with a protein tyrosine phosphatase (PTP) inhibitor. The electrophysiological correlate of the effects of DHPG in the SEP-GluA2 infected cultures was a reduction in mEPSC frequency with no change in amplitude. The implications of these findings for the initial mechanisms of expression of both NMDA receptor- and mGluR-induced LTD are discussed.
Feather barbs as a good source of mtDNA for bird species identification in forensic wildlife investigations
Authors: Speller Camilla F , Nicholas George P , Yang Dongya Y
Published: July 2011

Background

The ability to accurately identify bird species is crucial for wildlife law enforcement and bird-strike investigations. However, such identifications may be challenging when only partial or damaged feathers are available for analysis.

Results

By applying vigorous contamination controls and sensitive PCR amplification protocols, we found that it was feasible to obtain accurate mitochondrial (mt)DNA-based species identification with as few as two feather barbs. This minimally destructive DNA approach was successfully used and tested on a variety of bird species, including North American wild turkey (Meleagris gallopavo), Canada goose (Branta canadensis), blue heron (Ardea herodias) and pygmy owl (Glaucidium californicum). The mtDNA was successfully obtained from 'fresh' feathers, historic museum specimens and archaeological samples, demonstrating the sensitivity and versatility of this technique.

Conclusions

By applying appropriate contamination controls, sufficient quantities of mtDNA can be reliably recovered and analyzed from feather barbs. This previously overlooked substrate provides new opportunities for accurate DNA species identification when minimal feather samples are available for forensic analysis.
Mild-stretch mechanical ventilation upregulates toll-like receptor 2 and sensitizes the lung to bacterial lipopeptide
Authors: Charles Pierre-Emmanuel , Tissières Pierre , Barbar Saber Davide , Croisier Delphine , Dufour Julien , Dunn-Siegrist Irène , Chavanet Pascal , Pugin Jérôme
Published: July 2011

Introduction

Mechanical ventilation (MV) could prime the lung toward an inflammatory response if exposed to another insult such as bacterial invasion. The underlying mechanisms are not so far clear. Toll-like receptors (TLRs) allow the host to recognize selectively bacterial pathogens and in turn to trigger an immune response. We therefore hypothesized that MV modulates TLR2 expression and in turn modifies responsiveness to agonists such as bacterial lipopeptide (BLP).

Method

Both in vitro and in vivo experiments were conducted. First, TLR2 expression and protein were measured in the A549 pulmonary epithelial cell line submitted to 8-hour cyclic stretch (20% elongation; 20/minute rate). After a 24-hour period of cyclic stretch, the inflammatory response of the A549 cells to the synthetic BLP, Pam3CSK4, was tested after 8 hours of exposure. In a second set of experiments, healthy anesthetized and paralyzed rabbits were submitted to 8-hour MV (tidal volume = 12 ml/kg, zero end-expiratory pressure; FIO2 = 50%; respiratory rate = 20/minute) before being sacrificed for TLR2 lung expression assessment. The lung inflammatory response to BLP was then tested in animals submitted to 24-hour MV before being sacrificed 8 hours after the tracheal instillation of Pam3CSK4.

Results

Cyclic stretch of human pulmonary epithelial cell lines increased both TLR2 mRNA and protein expression. Cells submitted to cyclic stretch also increased IL-6 and IL-8 secretion in response to Pam3CSK4, a classical TLR2 ligand. A mild-stretch MV protocol induced a 60-fold increase of TLR2 mRNA expression in lung tissue when compared with spontaneously breathing controls. Moreover, the combination of MV and airway exposure to Pam3CSK4 acted synergistically in causing lung inflammation and injury.

Conclusions

Mild-stretch MV increases lung expression of TLR2 and sensitizes the lung to bacterial TLR2 ligands. This may account for the propensity of mechanically ventilated patients to develop acute lung injury in the context of airway bacterial colonization/infection.
Role of alloreactive KIR2DS1+ NK cells in haploidentical hematopoietic stem cell transplantation
Authors: Marcenaro Emanuela , Carlomagno Simona , Pesce Silvia , Della Chiesa Mariella , Moretta Alessandro , Sivori Simona
Published: July 2011

In allo-HSCT, donor-derived, ″alloreactive″ NK cells have been shown to play a crucial role in the treatment of acute leukemia, contributing to eradication of leukemic blasts (GvL effect) and to clearance of residual recipient DCs and T lymphocytes (thus, preventing GvHD and graft rejection, respectively). Such alloreactive NK cells do not express CD94/NKG2A but express inhibitory KIRs, specific for HLA class I allotypes, present in the donor but lacking in the recipient. This review is focused on the role of the activating KIR2DS1 receptor (specific for the C2-epitope of HLA-C) in haplo-HSCT. Recent data indicate that KIR2DS1 expression in HSC donors may represent a remarkable advantage in alloreactive NK responses. This is a result of a substantial increase in the NK-mediated capability to kill, not only recipients' leukemic cells but also DCs and T cell blasts. The beneficial effects mediated by alloreactive KIR2DS1+ NK cells may occur after de novo expression of CCR7 upon interaction with allogeneic, KIR ligand-mismatched CCR7+ cells. As a consequence, they can be redirected to LNs, where they can prevent priming of donor T cells and induction of GvHD. Finally, KIR2DS1 expression may also significantly amplify the size of the alloreactive NK cell subset by switching a subset of “not alloreactive” NK cells into potent alloreactive cells.
Postlesion Estradiol Treatment Increases Cortical Cholinergic Innervations via Estrogen Receptor-α Dependent Nonclassical Estrogen Signaling in Vivo
Authors: Kőszegi Zsombor , Szegő Éva M. , Cheong Rachel Y. , Tolod-Kemp Emeline , Ábrahám István M.
Published: July 2011

17β-Estradiol (E2) treatment exerts rapid, nonclassical actions via intracellular signal transduction system in basal forebrain cholinergic (BFC) neurons in vivo. Here we examined the effect of E2 treatment on lesioned BFC neurons in ovariectomized mice and the role of E2-induced nonclassical action in this treatment. Mice given an N-methyl-d-aspartic acid (NMDA) injection into the substantia innominata-nucleus basalis magnocellularis complex (SI-NBM) exhibited cholinergic cell loss in the SI-NBM and ipsilateral cholinergic fiber loss in the cortex. A single injection of E2 after NMDA lesion did not have an effect on cholinergic cell loss in the SI-NBM, but it restored the ipsilateral cholinergic fiber density in the cortex in a time- and dose-dependent manner. The most effective cholinergic fiber restoration was observed with 33 ng/g E2 treatment at 1 h after NMDA lesion. The E2-induced cholinergic fiber restoration was absent in neuron-specific estrogen receptor-α knockout mice in vivo. Selective activation of nonclassical estrogen signaling in vivo by estren induced E2-like restorative actions. Selective blockade of the MAPK or protein kinase A pathway in vivo prevented E2's ability to restore cholinergic fiber loss. Finally, studies in intact female mice revealed an E2-induced restorative effect that was similar to that of E2-treated ovariectomized mice. These observations demonstrate that a single E2 treatment restores the BFC fiber loss in the cortex, regardless of endogenous E2 levels. They also reveal the critical role of nonclassical estrogen signaling via estrogen receptor-α and protein kinase A-MAPK pathways in E2-induced restorative action in the cholinergic system in vivo.
Transcriptomic Analysis of the Osmotic and Reproductive Remodeling of the Female Rat Supraoptic Nucleus
Authors: Qiu Jing , Hindmarch Charles C. T. , Yao Song T. , Tasker Jeffrey G. , Murphy David
Published: July 2011

The supraoptic nucleus (SON) of the hypothalamus is an important integrative brain structure that coordinates responses to perturbations in water balance and regulates maternal physiology through the release of the neuropeptide hormones vasopressin and oxytocin into the circulation. Both dehydration and lactation evoke a dramatic morphological remodeling of the SON, a process known as function-related plasticity. We hypothesize that some of the changes seen in SON remodeling are mediated by differential gene expression, and have thus used microarrays to document global changes in transcript abundance that accompany chronic dehydration in female rats, and in lactation. In situ hybridization analysis has confirmed the differential expression of three of these genes, namely TNF-induced protein 6, gonadotropin-inducible transcription factor 1, and ornithine decarboxylase antizyme inhibitor 1. Comparison of differential gene expression patterns in male and female rats subjected to dehydration and in lactating rats has enabled the identification of common elements that are significantly enriched in gene classes with particular functions. Two of these are related to the requirement for increased protein synthesis and hormone delivery in the physiologically stimulated SON (translation initiation factor activity and endoplasmic reticulum-Golgi intermediate compartment, respectively), whereas others are consistent with the concept of SON morphological plasticity (collagen fibril organization, extracellular matrix organization and biogenesis, extracellular structure organization and biogenesis, and homophilic cell adhesion). We suggest that the genes coordinately regulated in the SON as a consequence of dehydration and lactation form a network that mediates the plastic processes operational in the physiologically activated SON.
A One-Year Randomized Trial of Lorcaserin for Weight Loss in Obese and Overweight Adults: The BLOSSOM Trial
Authors: Fidler Meredith C. , Sanchez Matilde , Raether Brian , Weissman Neil J. , Smith Steven R. , Shanahan William R. , Anderson Christen M.
Published: July 2011

Context:

Lorcaserin is a novel selective agonist of the serotonin 2C receptor.

Objective:

Our objective was to evaluate the effects of lorcaserin on body weight, cardiovascular risk factors, and safety in obese and overweight patients.

Design and Setting:

This randomized, placebo-controlled, double-blind, parallel arm trial took place at 97 U.S. research centers.

Patients:

Patients included 4008 patients, aged 18–65 yr, with a body mass index between 30 and 45 kg/m2 or between 27 and 29.9 kg/m2 with an obesity-related comorbid condition.

Interventions:

Patients were randomly assigned in a 2:1:2 ratio to receive lorcaserin 10 mg twice daily (BID), lorcaserin 10 mg once daily (QD), or placebo. All patients received diet and exercise counseling.

Main Outcome Measures:

The ordered primary endpoints were proportion of patients achieving at least 5% reduction in body weight, mean change in body weight, and proportion of patients achieving at least 10% reduction in body weight at 1 yr. Serial echocardiograms monitored heart valve function.

Results:

Significantly more patients treated with lorcaserin 10 mg BID and QD lost at least 5% of baseline body weight (47.2 and 40.2%, respectively) as compared with placebo (25.0%, P < 0.001 vs. lorcaserin BID). Least squares mean (95% confidence interval) weight loss with lorcaserin BID and QD was 5.8% (5.5–6.2%) and 4.7% (4.3–5.2%), respectively, compared with 2.8% (2.5–3.2%) with placebo (P < 0.001 vs. lorcaserin BID; least squares mean difference, 3.0%). Weight loss of at least 10% was achieved by 22.6 and 17.4% of patients receiving lorcaserin 10 mg BID and QD, respectively, and 9.7% of patients in the placebo group (P < 0.001 vs. lorcaserin BID). Headache, nausea, and dizziness were the most common lorcaserin-related adverse events. U.S. Food and Drug Administration-defined echocardiographic valvulopathy occurred in 2.0% of patients on placebo and 2.0% on lorcaserin 10 mg BID.

Conclusions:

Lorcaserin administered in conjunction with a lifestyle modification program was associated with dose-dependent weight loss that was significantly greater than with placebo.
Famine, Aid, and Ideology: The Political Activism of Médecins sans Frontières in the 1980s
Authors: Davey Eleanor
Published: July 2011

This article concerns humanitarian debates in France in the 1980s, in particular as inspired by the activism of the organization Médecins sans Frontières (MSF). It examines three episodes of debate about compromise and the complicity of humanitarian activism in totalitarian repression: a protest march at the Cambodian border in 1980, spearheaded by MSF; the creation by MSF in 1985 of a political think tank, the Fondation Liberté sans Frontières, with its inaugural conference attacking Third Worldism; and finally, MSF's stand in 1985 against the manipulation of aid by the Ethiopian government. It seeks to demonstrate how the realization of humanitarianism's vulnerability to manipulation emerged from a period of intensified, politically targeted activism. The analysis focuses on two key strands of debate: attitudes to ideology, specifically Third Worldist ideology, and the use of the media as part of the sans-frontiériste practice of témoignage.

Cet article porte sur les débats humanitaires en France pendant les années 1980, visant surtout les débats sur l'activisme de l'organisation Médecins sans frontières (MSF). Il présente trois épisodes dont le débat portait sur la compromission et la complicité de l'humanitarisme dans la répression totalitaire: une manifestation menée par MSF à la frontière cambodgienne en 1980; la création par la même organisation, en 1985, d'un centre de recherche politique, la Fondation Liberté sans frontières, avec son colloque inaugural s'attaquant au tiers-mondisme; et enfin la prise de position de MSF en 1985 contre la manipulation de l'aide humanitaire par le gouvernement éthiopien. Cet article cherche à démontrer comment, pendant la famine éthiopienne, l'articulation de la vulnérabilité de l'humanitarisme à la manipulation a été le résultat d'une période d'activisme politique intensifié. L'analyse se concentre sur deux motifs importants du débat: les attitudes envers l'idéologie, spécifiquement l'idéologie tiers-mondiste, et l'usage des médias comme partie intégrale de la pratique sans-frontiériste du témoignage.
Behind the Imperial Curtain: International Humanitarian Efforts and the Critique of French Colonialism in the Interwar Years
Authors: Daughton J. P.
Published: July 2011

This article examines the work of French critics of empire in the context of an international effort to minimize violence and suffering in Europe's colonies during the interwar years. Rather than highlight individual political motivations, the article considers the important similarities of these critics' works. Often writing in the style of documentary reportage and concerned with how policies caused suffering among non-European populations, authors as varied as Albert Londres, Félicien Challaye, and Paul Monet produced articles and books that critiqued colonial practices at their most fundamental level. They shared an interest in the impact of colonial rule with other European, American, and non-European individuals and institutions informally linked by the networks of the League of Nations and the International Labor Organization. The existence of these new networks removed key debates about colonialism from the national stage and opened them to the scrutiny of more international and, at times, anticolonial perspectives.

Cet article analyse les critiques françaises de l'empire d'outre-mer dans le contexte de l'effort international qui essayait de minimiser la violence et la misère des populations des colonies européennes pendant l'entre-deux-guerres. Au lieu de mettre en lumière les mobiles politiques individuels, l'article trace les ressemblances importantes entre certains ouvrages de ces critiques. Dans leurs articles et livres, Albert Londres, Félicien Challaye et Paul Monet critiquaient les pratiques coloniales dans leur aspect fondamental. Ecrits le plus souvent dans un style de reportage documentaire, ils témoignent d'une préoccupation concernant l'impact néfaste des politiques coloniales sur les populations autochtones. Par cette critique des effets de la politique coloniale, ils font preuve d'une affinité avec nombre d'individus et institutions européennes, américaines, et non européennes liés par des réseaux informels de la Société des nations et du Bureau international du travail. Finalement, l'apparition de ces nouveaux réseaux a déplacé ces débats importants sur le colonialisme de la scène nationale, pour les faire exposer à l'œil vigilant des groupes internationaux et/ou anticoloniaux.
Ezh2 regulates anteroposterior axis specification and proximodistal axis elongation in the developing limb
Authors: Wyngaarden Laurie A. , Delgado-Olguin Paul , Su I-hsin , Bruneau Benoit G. , Hopyan Sevan
Published: July 2011

Specification and determination (commitment) of positional identities precedes overt pattern formation during development. In the limb bud, it is clear that the anteroposterior axis is specified at a very early stage and is prepatterned by the mutually antagonistic interaction between Gli3 and Hand2. There is also evidence that the proximodistal axis is specified early and determined progressively. Little is known about upstream regulators of these processes or how epigenetic modifiers influence axis formation. Using conditional mutagenesis at different time points, we show that the histone methyltransferase Ezh2 is an upstream regulator of anteroposterior prepattern at an early stage. Mutants exhibit posteriorised limb bud identity. During later limb bud stages, Ezh2 is essential for cell survival and proximodistal segment elongation. Ezh2 maintains the late phase of Hox gene expression and cell transposition experiments suggest that it regulates the plasticity with which cells respond to instructive positional cues.
Notch-mediated repression of bantam miRNA contributes to boundary formation in the Drosophila wing
Authors: Becam Isabelle , Rafel Neus , Hong Xin , Cohen Stephen M. , Milán Marco
Published: July 2011

Subdivision of proliferating tissues into adjacent compartments that do not mix plays a key role in animal development. The Actin cytoskeleton has recently been shown to mediate cell sorting at compartment boundaries, and reduced cell proliferation in boundary cells has been proposed as a way of stabilizing compartment boundaries. Cell interactions mediated by the receptor Notch have been implicated in the specification of compartment boundaries in vertebrates and in Drosophila, but the molecular effectors remain largely unidentified. Here, we present evidence that Notch mediates boundary formation in the Drosophila wing in part through repression of bantam miRNA. bantam induces cell proliferation and we have identified the Actin regulator Enabled as a new target of bantam. Increased levels of Enabled and reduced proliferation rates contribute to the maintenance of the dorsal-ventral affinity boundary. The activity of Notch also defines, through the homeobox-containing gene cut, a distinct population of boundary cells at the dorsal-ventral (DV) interface that helps to segregate boundary from non-boundary cells and contributes to the maintenance of the DV affinity boundary.