bluuebunny/crossref_metadata_2025 huggingface dataset:
A role for miR-155 in enabling tumor-infiltrating innate immune cells to mount effective antitumor responses in mice
Authors: Zonari Erika , Pucci Ferdinando , Saini Massimo , Mazzieri Roberta , Politi Letterio S. , Gentner Bernhard , Naldini Luigi
Published: March 2013

Key Points

miR-155 knockdown in myeloid cells accelerates spontaneous breast cancer development. miR-155 is required by TAMs for deploying antitumoral activity.
CGAP: a new comprehensive platform for the comparative analysis of chloroplast genomes
Authors: Cheng Jinkui , Zeng Xu , Ren Guomin , Liu Zhihua
Published: March 2013

Background

Chloroplast is an essential organelle in plants which contains independent genome. Chloroplast genomes have been widely used for plant phylogenetic inference recently. The number of complete chloroplast genomes increases rapidly with the development of various genome sequencing projects. However, no comprehensive platform or tool has been developed for the comparative and phylogenetic analysis of chloroplast genomes. Thus, we constructed a comprehensive platform for the comparative and phylogenetic analysis of complete chloroplast genomes which was named as chloroplast genome analysis platform (CGAP).

Results

CGAP is an interactive web-based platform which was designed for the comparative analysis of complete chloroplast genomes. CGAP integrated genome collection, visualization, content comparison, phylogeny analysis and annotation functions together. CGAP implemented four web servers including creating complete and regional genome maps of high quality, comparing genome features, constructing phylogenetic trees using complete genome sequences, and annotating draft chloroplast genomes submitted by users.

Conclusions

Both CGAP and source code are available at http://www.herbbol.org:8000/chloroplast. CGAP will facilitate the collection, visualization, comparison and annotation of complete chloroplast genomes. Users can customize the comparative and phylogenetic analysis using their own unpublished chloroplast genomes.
A high throughput multiplex PCR assay for simultaneous detection of seven aminoglycoside-resistance genes in Enterobacteriaceae
Authors: Hu Xiumei , Xu Banglao , Yang Yinmei , Liu Dayu , Yang Mengjie , Wang Ji , Shen Hongwei , Zhou Xiaomian , Ma Xuejun
Published: March 2013

Background

The aminoglycoside-resistance genes encoding aminoglycoside modifying enzymes and 16S rRNA methyltransferases are main factors contributing to increasing resistance to aminoglycosides. Characterization and distribution of antimicrobial resistance gene profiles provide important information on the potential difficulty of treatment of bacteria. Several molecular methods have been developed to investigate the prevalence of aminoglycoside-resistance genes. These existing methods are time-consuming, labor-intensive, expensive or limited sensitivity in the epidemiological investigation. Therefore, it is necessary to develop a rapid, less-costly and high throughput and sensitive method to investigate the distribution of antimicrobial resistance gene in clinical isolates.

Results

In this study, we developed a GeXP analyzer-based multiplex PCR assay to simultaneously detect seven aminoglycoside-resistance genes, including aac(3)-II, aac(6′
)-Ib, aac(6′
)-II, ant(3″
)-I,
aph(3′
)-VI,
armA and rmtB, and to analyze the distribution of these genes in clinical Enterobacteriaceae isolates. Under optimized conditions, this assay achieved a limit-of-detection as low as 10 copies of each of the seven genes. The presented method was applied to analyze the distribution of aminoglycoside-resistance genes in 56 clinical Enterobacteriaceae isolates, and the results were compared with that of the conventional single PCR assay. Kappa values of the two methods for detecting each of the seven resistance genes were 0.831, 0.846, 0.810, 0.909, 0.887, 0.810 and 0.825, respectively.

Conclusion

This GeXP assay is demonstrated to be a rapid, cost-effective and high throughput method with high sensitivity and specificity for simultaneously detecting seven common aminoglycoside-resistance genes.
Observation of sonified movements engages a basal ganglia frontocortical network
Authors: Schmitz Gerd , Mohammadi Bahram , Hammer Anke , Heldmann Marcus , Samii Amir , Münte Thomas F , Effenberg Alfred O
Published: March 2013

Background

Producing sounds by a musical instrument can lead to audiomotor coupling, i.e. the joint activation of the auditory and motor system, even when only one modality is probed. The sonification of otherwise mute movements by sounds based on kinematic parameters of the movement has been shown to improve motor performance and perception of movements.

Results

Here we demonstrate in a group of healthy young non-athletes that congruently (sounds match visual movement kinematics) vs. incongruently (no match) sonified breaststroke movements of a human avatar lead to better perceptual judgement of small differences in movement velocity. Moreover, functional magnetic resonance imaging revealed enhanced activity in superior and medial posterior temporal regions including the superior temporal sulcus, known as an important multisensory integration site, as well as the insula bilaterally and the precentral gyrus on the right side. Functional connectivity analysis revealed pronounced connectivity of the STS with the basal ganglia and thalamus as well as frontal motor regions for the congruent stimuli. This was not seen to the same extent for the incongruent stimuli.

Conclusions

We conclude that sonification of movements amplifies the activity of the human action observation system including subcortical structures of the motor loop. Sonification may thus be an important method to enhance training and therapy effects in sports science and neurological rehabilitation.
Active inclusion bodies of acid phosphatase PhoC: aggregation induced by GFP fusion and activities modulated by linker flexibility
Authors: Huang Ziliang , Zhang Chong , Chen Shuo , Ye Fengchun , Xing Xin-Hui
Published: March 2013

Background

Biologically active inclusion bodies (IBs) have gained much attention in recent years. Fusion with IB-inducing partner has been shown to be an efficient strategy for generating active IBs. To make full use of the advantages of active IBs, one of the key issues will be to improve the activity yield of IBs when expressed in cells, which would need more choices on IB-inducing fusion partners and approaches for engineering IBs. Green fluorescent protein (GFP) has been reported to aggregate when overexpressed, but GFP fusion has not been considered as an IB-inducing approach for these fusion proteins so far. In addition, the role of linker in fusion proteins has been shown to be important for protein characteristics, yet impact of linker on active IBs has never been reported.

Results

Here we report that by fusing GFP and acid phosphatase PhoC via a linker region, the resultant PhoC-GFPs were expressed largely as IBs. These IBs show high levels of specific fluorescence and specific PhoC activities (phosphatase and phosphotransferase), and can account for up to over 80% of the total PhoC activities in the cells. We further demonstrated that the aggregation of GFP moiety in the fusion protein plays an essential role in the formation of PhoC-GFP IBs. In addition, PhoC-GFP IBs with linkers of different flexibility were found to exhibit different levels of activities and ratios in the cells, suggesting that the linker region can be utilized to manipulate the characteristics of active IBs.

Conclusions

Our results show that active IBs of PhoC can be generated by GFP fusion, demonstrating for the first time the potential of GFP fusion to induce active IB formation of another soluble protein. We also show that the linker sequence in PhoC-GFP fusion proteins plays an important role on the regulation of IB characteristics, providing an alternative and important approach for engineering of active IBs with the goal of obtaining high activity yield of IBs.
Dose–response tests and semi-field evaluation of lethal and sub-lethal effects of slow release pyriproxyfen granules (Sumilarv®0.5G) for the control of the malaria vectors Anopheles gambiae sensu lato
Authors: Mbare Oscar , Lindsay Steven W , Fillinger Ulrike
Published: March 2013

Background

Recently research has shown that larviciding can be an effective tool for integrated malaria vector control. Nevertheless, the uptake of this intervention has been hampered by the need to re-apply larvicides frequently. There is a need to explore persistent, environmentally friendly larvicides for malaria vector control to reduce intervention efforts and costs by reducing the frequency of application. In this study, the efficacy of a 0.5% pyriproxyfen granule (Surmilarv®0.5G, Sumitomo Chemicals) was assessed for the control of Anopheles gambiae sensu stricto and Anopheles arabiensis, the major malaria vectors in sub-Saharan Africa.

Methods

Dose–response and standardized field tests were implemented following standard procedures of the World Health Organization’s Pesticide Evaluation Scheme to determine: (i) the susceptibility of vectors to this formulation; (ii) the residual activity and appropriate retreatment schedule for field application; and, (iii) sub-lethal impacts on the number and viability of eggs laid by adults after exposure to Sumilarv®0.5G during larval development.

Results

Anopheles gambiae s.s. and An. arabiensis were highly susceptible to Sumilarv®0.5G. Estimated emergence inhibition (EI) values were very low and similar for both species. The minimum dosage that completely inhibited adult emergence was between 0.01-0.03 parts per million (ppm) active ingredient (ai). Compared to the untreated control, an application of 0.018 ppm ai prevented 85% (95% confidence interval (CI) 82%-88%) of adult emergence over six weeks under standardized field conditions. A fivefold increase in dosage of 0.09 ppm ai prevented 97% (95% CI 94%-98%) emergence. Significant sub-lethal effects were observed in the standardized field tests. Female An. gambiae s.s. that were exposed to 0.018 ppm ai as larvae laid 47% less eggs, and females exposed to 0.09 ppm ai laid 74% less eggs than females that were unexposed to the treatment. Furthermore, 77% of eggs laid by females exposed to 0.018 ppm ai failed to hatch, whilst 98% of eggs laid by females exposed to 0.09 ppm ai did not hatch.

Conclusion

Anopheles gambiae s.s. and An. arabiensis are highly susceptible to Sumilarv®0.5G at very low dosages. The persistence of this granule formulation in treated habitats under standardized field conditions and its sub-lethal impact, reducing the number of viable eggs from adults emerging from treated ponds, enhances its potential as malaria vector control tool. These unique properties warrant further field testing to determine its suitability for inclusion in malaria vector control programmes.
Induction chemotherapy in patients with resectable head and neck squamous cell carcinoma: a meta-analysis
Authors: Ma Jie , Liu Ying , Yang Xi , Zhang Chen-ping , Zhang Zhi-yuan , Zhong Lai-ping
Published: March 2013

Background

Induction chemotherapy has been investigated as a possible strategy to shrink or downstage locally advanced head and neck cancers, providing opportunity to remove the lesions completely after induction chemotherapy, especially in the patients with resectable advanced disease. The aim of this study was to investigate the definitive effect of induction chemotherapy in patients with resectable head and neck squamous cell carcinoma.

Methods

A meta-analysis of randomized trials (1965–2011) was performed on the impact of induction chemotherapy on survival, disease control, and toxicity in this population of patients. Kaplan-Meier curves were read by Engauge-Digitizer. Data combining was performed using RevMan.

Results

Fourteen trials (2099 patients) were involved in this analysis. There was no significant difference on overall survival, disease free survival, or locoregional recurrence between the patients treated with and without induction chemotherapy (P >0.05). However, the patients treated with induction chemotherapy had a lower rate of distant metastasis by 8% (95% confidence interval 1%–16%, P = 0.02) than those treated without induction chemotherapy. In patients with laryngeal cancer, comparing to radical surgery, the larynx could be preserved in responders to induction chemotherapy without survival decease (P >0.05). Induction chemotherapy-associated death was 0%–5%.

Conclusions

Based on the results above, there is a significant benefit of induction chemotherapy on decreasing distant metastasis in patients with resectable head and neck squamous cell carcinoma. In patients with laryngeal cancer, induction chemotherapy provides larynx preservation in responders to induction chemotherapy.
Protocol design and performance analysis for cognitive cooperative networks with multiple antennas
Authors: Huang Yuzhen , Wu Qihui , Wang Jinlong , Cheng Yunpeng
Published: March 2013

In this article, we deal with a novel access protocol design for cognitive cooperative networks with multiple antennas. According to the principles of cognitive radio, the secondary user (SU) can exploit the primary user (PU) burstiness to access the licensed spectrum in the proposed access protocol. To get more access opportunities to the licensed spectrum, the SU simultaneously relays the PU’s packets and transmits its own packets based on the superposition coding. Furthermore, to concurrent transmission of the PU’s packets and SU’s packets based on the superposition coding such that they are received without the interference at the primary receiver and secondary receiver respectively, two weight vectors at the SU equipped with multiple antennas are designed based on zero-forcing algorithm. Specifically, from a networking perspective, we analyze the performance of the proposed access protocol in terms of the maximum stable throughput and the average end-to-end delay for both the PU and SU based on the principles of queueing theory. In addition, to protect the PU’s performance and exhibit the advantage of adopting multiple antenna technology, we jointly optimize the parameter of superposition coding and the number of antennas, and define the maximum stable throughput cooperative gain compared to the non-cooperative access scheme. More importantly, the impact of imperfect channel state information (CSI) at the SU on the maximum stable throughput and the average end-to-end delay performance is evaluated in the simulations from a practical point of view. Analysis and simulation results demonstrate that the proposed access protocol achieves significant performance gains for both the PU and the SU, outperforms the existing cooperative access protocol based on the dirty-paper coding, and keeps robust against to the imperfect CSI.
Rapid resolution of acute subdural hematoma in child with severe head injury: a case report
Authors: Park Jae-Young , Moon Kyung-Sub , Lee Jung-Kil , Jeung Kyung-Woon
Published: March 2013

Introduction

Rapid spontaneous resolution of traumatic acute subdural hematoma is an infrequent phenomenon and mainly develops in a case of simple acute subdural hematoma without parenchymal contusion. However, it has been rarely reported in a pediatric case with severe initial head injury.

Case presentation

A 7-year-old Asian girl with traumatic acute subdural hematoma was transferred to our hospital for an emergency operation based on the results of an initial computed tomography scan and neurological examination. However, a repeat computed tomography scan two hours after trauma disclosed considerable reduction of the hematoma and midline shift with neurological improvements. Serial follow-up imaging studies demonstrated apparent redistribution of the hematoma over the cerebellar tentorium, posterior interhemispheric fissure and subarachnoid space. The patient was discharged with mild confusion 40 days after the admission.

Conclusion

A follow-up computed tomography scan is strongly recommended before surgery when a child with a severe head injury presents with any sign of neurological improvement, especially with a mixed density hematoma on the initial computed tomography scan.
Recurrent visceral leishmaniasis in an immunocompetent patient: a case report
Authors: Lagadinou Maria , Dimitropoulou Dimitra , Assimakopoulos Stelios F , Davoulos George , Marangos Markos
Published: March 2013

Introduction

Current treatment options for visceral leishmaniasis (pentavalent antimony, amphotericin B, liposomal amphotericin B and mitelfosine) achieve long-term clinical cure in the majority of immunocompetent patients. Disease relapse is usually provoked by T-cell number or function impairment (corticosteroid or cytotoxic therapy, transplant recipients, advanced human immunodeficiency virus disease).

Case presentation

We report a case of visceral leishmaniasis with multiple relapses in a 75-year-old Greek immunocompetent man. Visceral leishmaniasis relapses occurred despite appropriate treatment with liposomal amphotericin B 3mg/kg/day on days one to five, 14 and 21 (for the first episode and the first relapse) and mitelfosine 150mg/day for 28 days (for the second relapse). The third relapse was treated with high-dose liposomal amphotericin B (10mg/kg for two consecutive days), followed by a secondary prophylaxis of 3mg/kg once per month, which prevented disease reappearance during one year of follow-up.

Conclusion

An unusual case of recurrent visceral leishmaniasis in an older immunocompetent patient was treated with high-dose liposomal amphotericin B and a monthly prophylaxis with no evidence of a relapse after one year of follow-up.
Postoperative neurological aggravation after anesthesia with sevoflurane in a patient with xeroderma pigmentosum: a case report
Authors: Fjouji Salaheddine , Bensghir Mustapha , Yafat Bahija , Bouhabba Najib , Boutayeb Elhoucine , Azendour Hicham , Kamili Nordine Drissi
Published: March 2013

Introduction

Xeroderma pigmentosum is a rare autosomal recessive disease that causes changes in skin pigmentation, precancerous lesions and neurological abnormalities. It is a defect in the nucleotide excision repair mechanism. It has been reported that volatile anesthetics has a possible genotoxic side effect and deranged nucleotide excision repair in cells obtained from a patient with xeroderma pigmentosum.

We report an unusual case of postoperative neurological aggravation in a patient with xeroderma pigmentosum anesthetized with sevoflurane.

Case presentation

A 24-year-old African woman, who has had xeroderma pigmentosum since childhood, was admitted to our hospital for a femoral neck fracture. A preoperative physical examination revealed that she had a resting tremor with ataxia. She had cutaneous lesions such as keratosis and hyperpigmentation on her face and both hands. There was no major alteration of cognitive function, muscular strength was maintained and her osteotendinous reflexes were preserved. Surgical fixation was performed under general anesthesia after the failure of spinal anesthesia. All parameters were stable during surgery. When she woke up four hours later, the patient presented with confusion and psychomotor agitation, sharpened reflexes and the Babinski reflex was present. Her postoperative test results and a magnetic resonance imaging scan were unremarkable. It was suggested that sevoflurane had had a probable deleterious effect on the neurological status of this patient.

Conclusion

The anesthetizing of a patient with xeroderma pigmentosum is associated with a risk of worsening neurological disorders. At present, there are no clear recommendations to avoid the use of volatile agents in the anesthetic management of patients with xeroderma pigmentosum. More clinical and experimental research is needed to confirm the sensitivity of patients with xeroderma pigmentosum to sevoflurane and other halogenated anesthetics.
Recombinant Arthrobacter β-1, 3-glucanase as a potential effector molecule for paratransgenic control of Chagas disease
Authors: Jose Christo , Klein Nicole , Wyss Sarah , Fieck Annabeth , Hurwitz Ivy , Durvasula Ravi
Published: March 2013

Background

Chagas disease is most often transmitted to humans by Trypanosoma cruzi infected triatomine bugs, and remains a significant cause of morbidity and mortality in Central and South America. Control of Chagas disease has relied mainly on vector eradication. However, development of insect resistance has prompted us to develop a paratransgenic strategy to control vectorial transmission of T. cruzi. Here, the potential role of recombinant endoglucanases as anti-trypanosomal agents for paratransgenic application is examined. The surface of T. cruzi is covered by a thick coat of mucin-like glycoproteins that have been proposed to play a role in the binding of T. cruzi to the membrane surface of the vector gut. We hypothesize that disruption of these glycoconjugates could arrest parasite development in the vector and abort the transmission cycle. In this work, we examine the effects of recombinant Arthrobacter luteus β-1, 3-glucanase expressed via Rhodococcus rhodnii on T. cruzi Sylvio II strain.

Methods and results

The coding sequence for β-1, 3-glucanase was cloned in-frame to a heterologous promoter/signal sequence from the Mycobacterium kansasii alpha antigen gene resident in an E. coli/R. rhodnii shuttle vector. The resulting construct was confirmed by sequencing, and electroporated into R. rhodnii. Expression products from positive clones were purified from log phase cultures followed by dialysis into physiological buffers. Lysates and media were quantitated by ELISA against rabbit antibody specific to β-1,3-glucanase. Glucanase-positive samples were applied to live T. cruzi parasites in culture and viability accessed by spectrophotometric and fluorescent microscopic measurements. R. rhodnii-expressed β-1,3-glucanase exhibited toxicity against T. cruzi compared to controls when applied at 5 and 10% of the total culture volume. The decrease in cell viability ranged from a maximum of 50% for the media treatments to 80% for the filtered lysates.

Conclusions

These results suggest that recombinant β-glucanase could be a powerful addition to the arsenal of effector molecules for paratransgenic control of Chagas disease. In future studies, the ability of β-glucanase to function in combination with other effector molecules will be explored. Dual targeting of T. cruzi should not only slow resistance but also permit synergistic or additive lethal effects on T. cruzi.
Tcf7l1 prepares epiblast cells in the gastrulating mouse embryo for lineage specification
Authors: Hoffman Jackson A. , Wu Chun-I , Merrill Bradley J.
Published: March 2013

The core gene regulatory network (GRN) in embryonic stem cells (ESCs) integrates activities of the pro-self-renewal factors Oct4 (Pou5f1), Sox2 and Nanog with that of an inhibitor of self-renewal, Tcf7l1 (Tcf3). The inhibitor function of Tcf7l1 causes dependence on extracellular Wnt/β-catenin signaling activity, making its embryonic role within the ESC GRN unclear. By analyzing intact mouse embryos, we demonstrate that the function of Tcf7l1 is necessary for specification of cell lineages to occur concomitantly with the elaboration of a three-dimensional body plan during gastrulation. In Tcf7l1-/- embryos, specification of mesoderm is delayed, effectively uncoupling it from the induction of the primitive streak. Tcf7l1 repressor activity is necessary for a rapid switch in the response of pluripotent cells to Wnt/β-catenin stimulation, from one of self-renewal to a mesoderm specification response. These results identify Tcf7l1 as a unique factor that is necessary in pluripotent cells to prepare them for lineage specification. We suggest that the role of Tcf7l1 in mammals is to inhibit the GRN to ensure the coordination of lineage specification with the dynamic cellular events occurring during gastrulation.
De novo lumen formation and elongation in the developing nephron: a central role for afadin in apical polarity
Authors: Yang Zhufeng , Zimmerman Susan , Brakeman Paul R. , Beaudoin Gerard M. , Reichardt Louis F. , Marciano Denise K.
Published: March 2013

A fundamental process in biology is the de novo formation and morphogenesis of polarized tubules. Although these processes are essential for the formation of multiple metazoan organ systems, little is known about the molecular mechanisms that regulate them. In this study, we have characterized several steps in tubule formation and morphogenesis using the mouse kidney as a model system. We report that kidney mesenchymal cells contain discrete Par3-expressing membrane microdomains that become restricted to an apical domain, coinciding with lumen formation. Once lumen formation has been initiated, elongation occurs by simultaneous extension and additional de novo lumen generation. We demonstrate that lumen formation and elongation require afadin, a nectin adaptor protein implicated in adherens junction formation. Mice that lack afadin in nephron precursors show evidence of Par3-expressing membrane microdomains, but fail to develop normal apical-basal polarity and generate a continuous lumen. Absence of afadin led to delayed and diminished integration of nectin complexes and failure to recruit R-cadherin. Furthermore, we demonstrate that afadin is required for Par complex formation. Together, these results suggest that afadin acts upstream of the Par complex to regulate the integration and/or coalescence of membrane microdomains, thereby establishing apical-basal polarity and lumen formation/elongation during kidney tubulogenesis.
PUF-8 negatively regulates RAS/MAPK signalling to promote differentiation ofC. elegansgerm cells
Authors: Vaid Samir , Ariz Mohd , Chaturbedi Amaresh , Kumar Ganga Anil , Subramaniam Kuppuswamy
Published: March 2013

Signals that promote germ cell self-renewal by preventing premature meiotic entry are well understood. However, signals that control mitotic proliferation to promote meiotic differentiation have not been well characterized. In Caenorhabditis elegans, GLP-1 Notch signalling promotes the proliferative fate by preventing premature meiotic entry. The germline niche cell, which is the source of the ligand for GLP-1, spatially restricts GLP-1 signalling and thus enables the germ cells that have moved away from the niche to enter meiosis. Here, we show that the suppression of RAS/MAP kinase signalling in the mitotic and meiotic-entry regions is essential for the regulation of the mitosis-meiosis switch by niche signalling. We provide evidence that the conserved PUF family RNA-binding protein PUF-8 and the RAS GAP protein GAP-3 function redundantly to suppress the LET-60 RAS in the mitotic and meiotic entry regions. Germ cells missing both PUF-8 and GAP-3 proliferate in an uncontrolled fashion and fail to undergo meiotic development. MPK-1, the MAP kinase downstream of the LET-60 RAS, is prematurely activated in these cells; downregulation of MPK-1 activation eliminates tumours and restores differentiation. Our results further reveal that PUF-8 negatively regulates LET-60 expression at a post-transcriptional step. LET-60 is misexpressed in the puf-8(-) mutant germlines and PUF-8 physically interacts with the let-60 3′ UTR. Furthermore, PUF-8 suppresses let-60 3′ UTR-mediated expression in the germ cells that are transitioning from the mitotic to meiotic fate. These results reveal that PUF-8-mediated inhibition of the RAS/MAPK pathway is essential for mitotic-to-meiotic fate transition.
Cftr controls lumen expansion and function of Kupffer’s vesicle in zebrafish
Authors: Navis Adam , Marjoram Lindsay , Bagnat Michel
Published: March 2013

Regulated fluid secretion is crucial for the function of most organs. In vertebrates, the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) is a master regulator of fluid secretion. Although the biophysical properties of CFTR have been well characterized in vitro, little is known about its in vivo role during development. Here, we investigated the function of Cftr during zebrafish development by generating several cftr mutant alleles using TAL effector nucleases. We found that loss of cftr function leads to organ laterality defects. In zebrafish, left-right (LR) asymmetry requires cilia-driven fluid flow within the lumen of Kupffer’s vesicle (KV). Using live imaging we found that KV morphogenesis is disrupted in cftr mutants. Loss of Cftr-mediated fluid secretion impairs KV lumen expansion leading to defects in organ laterality. Using bacterial artificial chromosome recombineering, we generated transgenic fish expressing functional Cftr fusion proteins with fluorescent tags under the control of the cftr promoter. The transgenes completely rescued the cftr mutant phenotype. Live imaging of these transgenic lines showed that Cftr is localized to the apical membrane of the epithelial cells in KV during lumen formation. Pharmacological stimulation of Cftr-dependent fluid secretion led to an expansion of the KV lumen. Conversely, inhibition of ion gradient formation impaired KV lumen inflation. Interestingly, cilia formation and motility in KV were not affected, suggesting that fluid secretion and flow are independently controlled in KV. These findings uncover a new role for cftr in KV morphogenesis and function during zebrafish development.
Divergent roles for Wnt/β-catenin signaling in epithelial maintenance and breakdown during semicircular canal formation
Authors: Rakowiecki Staci , Epstein Douglas J.
Published: March 2013

The morphogenetic program that shapes the three semicircular canals (SSCs) must be executed with extreme precision to satisfy their complex vestibular function. The SSCs emerge from epithelial outgrowths of the dorsal otocyst, the central regions of which fuse and resorb to leave three fluid-filled canals. The Wnt/β-catenin signaling pathway is active at multiple stages of otic development, including during vestibular morphogenesis. How Wnt/β-catenin functionally integrates with other signaling pathways to sculpt the SSCs and their sensory patches is unknown. We used a genetic strategy to spatiotemporally modulate canonical Wnt signaling activity during SSC development in mice. Our findings demonstrate that Wnt/β-catenin signaling functions in a multifaceted manner during SSC formation. In the early phase, Wnt/β-catenin signaling is required to preserve the epithelial integrity of the vertical canal pouch perimeter (presumptive anterior and posterior SSCs) by establishing a sensory-dependent signaling relay that maintains expression of Dlx5 and opposes expression of the fusion plate marker netrin 1. Without this Wnt signaling activity the sensory to non-sensory signaling cascade fails to be activated, resulting in loss of vestibular hair and support cells and the anterior and posterior SSCs. In the later phase, Wnt/β-catenin signaling becomes restricted to the fusion plate where it facilitates the timely resorption of this tissue. Mosaic recombination of β-catenin in small clusters of canal pouch cells prevents their resorption, causing instead the formation of ectopic SSCs. Together, these disparate functions of the Wnt/β-catenin pathway in epithelial maintenance and resorption help regulate the size, shape and number of SSCs.
Hopx expression defines a subset of multipotent hair follicle stem cells and a progenitor population primed to give rise to K6+ niche cells
Authors: Takeda Norifumi , Jain Rajan , LeBoeuf Matthew R. , Padmanabhan Arun , Wang Qiaohong , Li Li , Lu Min Min , Millar Sarah E. , Epstein Jonathan A.
Published: March 2013

The mammalian hair follicle relies on adult resident stem cells and their progeny to fuel and maintain hair growth throughout the life of an organism. The cyclical and initially synchronous nature of hair growth makes the hair follicle an ideal system with which to define homeostatic mechanisms of an adult stem cell population. Recently, we demonstrated that Hopx is a specific marker of intestinal stem cells. Here, we show that Hopx specifically labels long-lived hair follicle stem cells residing in the telogen basal bulge. Hopx+ cells contribute to all lineages of the mature hair follicle and to the interfollicular epidermis upon epidermal wounding. Unexpectedly, our analysis identifies a previously unappreciated progenitor population that resides in the lower hair bulb of anagen-phase follicles and expresses Hopx. These cells co-express Lgr5, do not express Shh and escape catagen-induced apoptosis. They ultimately differentiate into the cytokeratin 6-positive (K6) inner bulge cells in telogen, which regulate the quiescence of adjacent hair follicle stem cells. Although previous studies have suggested that K6+ cells arise from Lgr5-expressing lower outer root sheath cells in anagen, our studies indicate an alternative origin, and a novel role for Hopx-expressing lower hair bulb progenitor cells in contributing to stem cell homeostasis.
Force generation by kinesin and myosin cytoskeletal motor proteins
Authors: Kull F. Jon , Endow Sharyn A.
Published: March 2013

Kinesins and myosins hydrolyze ATP, producing force that drives spindle assembly, vesicle transport and muscle contraction. How do motors do this? Here we discuss mechanisms of motor force transduction, based on their mechanochemical cycles and conformational changes observed in crystal structures. Distortion or twisting of the central β-sheet – proposed to trigger actin-induced Pi and ADP release by myosin, and microtubule-induced ADP release by kinesins – is shown in a movie depicting the transition between myosin ATP-like and nucleotide-free states. Structural changes in the switch I region form a tube that governs ATP hydrolysis and Pi release by the motors, explaining the essential role of switch I in hydrolysis. Comparison of the motor power strokes reveals that each stroke begins with the force-amplifying structure oriented opposite to the direction of rotation or swing. Motors undergo changes in their mechanochemical cycles in response to small-molecule inhibitors, several of which bind to kinesins by induced fit, trapping the motors in a state that resembles a force-producing conformation. An unusual motor activator specifically increases mechanical output by cardiac myosin, potentially providing valuable information about its mechanism of function. Further study is essential to understand motor mechanochemical coupling and energy transduction, and could lead to new therapies to treat human disease.
BAL1/ARTD9 represses the anti-proliferative and pro-apoptotic IFNγ-STAT1-IRF1-53 axes in diffuse large B-cell lymphoma
Authors: Camicia Rosalba , Bachmann Samia B. , Winkler Hans C. , Beer Marc , Tinguely Marianne , Haralambieva Eugenia , Hassa Paul O.
Published: March 2013

The B-aggressive lymphoma-1 protein and ADP-ribosyltransferase BAL1/ARTD9 has been recently identified as a novel risk-related gene product in aggressive diffuse large B-cell lymphoma (DLBCL). BAL1 is constitutively expressed in a subset of high-risk DLBCL with an active host inflammatory response and suggested to be associated with interferon related gene expression. Here we identify BAL1 as a novel oncogenic survival factor in DLBCL and show that constitutive overexpression of BAL1 in DLBCL tightly associates with intrinsic interferon-gamma (IFNγ) signaling and constitutive activity of signal transducer and activator of transcription (STAT)-1. Remarkably, BAL1 stimulates the phosphorylation of both STAT1 isoforms STAT1α and STAT1β, on Y701 and thereby promoting the nuclear accumulation of the antagonistically acting and transcriptionally repressive isoform STAT1β. Moreover, BAL1 physically interacts with both isoforms of STAT1, STAT1α and STAT1β through its macro domains in an ADP-ribosylation dependent manner. BAL1 directly inhibits together with STAT1β the expression of tumor suppressor and interferon response factor (IRF)-1. Conversely, BAL1 enhances the expression of the proto-oncogenes IRF2 and B-cell CLL/lymphoma (BCL)-6 in DLBCL. Our results show the first time that BAL1 represses the anti-proliferative and pro-apoptotic IFNγ-STAT1-IRF1-53 axes and mediates proliferation, survival and chemo-resistance in DLBCL. As a consequence constitutive IFNγ-STAT1 signaling does not lead to apoptosis but rather to chemo-resistance in DLBCL overexpressing BAL1. Our results suggest that BAL1 may induce an oncogenic switch in STAT1 from a tumor suppressor to an oncogene in high-risk DLBCL.
Activity-dependent synaptic localization of processing bodies and their role in dendritic structural plasticity
Authors: Oh Jun-Young , Kwon Ara , Jo Anna , Kim Hoon , Goo Yong-Sook , Lee Jin-A , Kim Hyong Kyu
Published: March 2013

In neurons, transport of a subset of mRNAs to subcellular regions and their translation has a role in synaptic plasticity. Recent studies have suggested a control mechanism of this local translation through mRNA compartmentalization or degradation. Here we report that processing bodies (P-bodies), which are involved in mRNA degradation or storage, are transported to dendrites by conventional kinesin (KIF5A) as a motor protein. Neuronal activation induced by depolarization increased the co-localization of P-bodies with PSD-95 in dendrites. This neuronal activity increased the release of Nd1 and Arp2 mRNA from the P-bodies, and consequently reversed the decrease of F-actin, induced by overexpression of Dcp1a, in the dendrites. Our data suggest that the activity-induced redistribution of P-bodies and mRNA release from P-bodies may have a role in synaptic structural plasticity by altering levels of mRNAs, which are involved in the dynamics of the actin cytoskeleton in dendrites.
Endovascular aortic stent graft infection with Streptococcus equi: the first documented case
Authors: Parmar Jitesh , Winterbottom Andrew , Cooke Fiona , Lever Andrew M L , Gaunt Michael
Published: March 2013

Streptococcus equi is a common equine infectious disease, but transmission to man is rare and confined to those who commonly come into close contact with horses. Similarly, prosthetic stent graft infection is a rare complication of endovascular aortic aneurysm repair. We describe the first reported case of aortic stent graft with S. equi occurring in a professional racehorse trainer. Clinical presentation, investigations, imaging and management of this case are described. In conclusion, clinicians should consider infection with rare organisms in patients with prosthetic implants who regularly come into contact with horses and other ruminants.
Brachial artery transection associated with open elbow dislocation in a 12-year-old: a case report
Authors: Nazli Yunus , Colak Necmettin , Uras Ismail , Komurcu Mahmut , Cakir Omer
Published: March 2013

Although acute elbow dislocations are common orthopedic injuries, concomitant neurovascular injury is rare. Brachial artery transection can result from open elbow dislocation and responds well to vascular repair. Rapid evaluation and a high level of suspicion are essential to facilitate immediate treatment. Delay to identify vascular injury after elbow dislocation or reduction can potentially lead to limb ischemia, and potential loss of limb. We present a case of relatively rare transection of the brachial artery, with an accompanying traumatic open elbow dislocation in a 12-year-old boy.
Compression of the dorsalis pedis artery: a novel cause of blue toe syndrome
Authors: Griffin K J , Rankine J , Kessel D , Berridge D C , Scott D J A
Published: March 2013

Blue toe syndrome (BTS) is an important vascular condition characterized by painful blue discoloration of one or more digits. It is frequently due to emboli and is important because of the risk of progressive ischemia and tissue loss. A 53-year-old male presented with recurrent episodes of painful blue discoloration and blistering of the skin of the right hallux. On examination, the patient was found to have a cool, blue-purple great toe; all peripheral pulses were present. The patient was investigated for coagulopathy and potential sources of emboli, but the only abnormality was significant stenosis of the dorsalis pedis artery due to extrinsic compression by the extensor hallucis brevis tendon. In the absence of any other embolic source or abnormality, we believe that this case presents a novel and potentially remediable cause of BTS and indicates the need for a careful search for an underlying lesion when common causes of BTS have been excluded.
Pulse wave velocity and the non-invasive methods used to assess it: Complior, SphygmoCor, Arteriograph and Vicorder
Authors: Davies Jennifer M , Bailey Marc A , Griffin Kathryn J , Scott D Julian A
Published: March 2013

Pulse wave velocity (PWV) is a known indicator of arterial stiffness and cardiovascular risk. We critically evaluated the evidence supporting the four main non-invasive devices available to assess it: Complior, SphygmoCor, Arteriograph and Vicorder. PubMed and Medline databases (1960–2011) were searched to identify studies reporting carotid–femoral PWV in humans using one or more of the four devices. Of the 183 articles retrieved, 43 met inclusion criteria. The Arteriograph device demonstrated least variance but had poor agreement with the other devices. Undisputable reference values for PWV need to be established and internationally agreed, and a standardized method for superficial distance measurement generated to reduce variability. Further studies comparing all four devices with invasive assessment are necessary.
Pathophysiology and treatment of edema following femoropopliteal bypass surgery
Authors: Slaa A Te , Dolmans D E J G J , Ho G H , Moll F L , Van Der Laan L
Published: March 2013

Substantial lower-limb edema affects the majority of patients who undergo peripheral bypass surgery. Edema has impairing effects on the microvascular and the macrovascular circulation, causes discomfort and might delay the rehabilitation process of the patient. However, the pathophysiology of this edema is not well understood. The Cochrane Library and Medline were used to retrieve literature on edema following peripheral bypass surgery. Factors other than local wound healing alone are suggested in the literature to play a role, given the severity and duration of this edema. Hyperemia, microvascular permeability, reperfusion-associated inflammation and lymphatic disruptions are likely to facilitate the development of edema. Preventive methods could be lymphatic-sparing surgery, intraoperative antioxidative therapy and postoperative elevation. Successful treatment strategies to reduce postoperative edema are based on lymph massage and external compression. In conclusion, the pathophysiology of edema following peripheral surgery is not fully understood, although reperfusion-associated inflammation and lymphatic disruptions are likely to play a crucial role. When future less-invasive techniques prove to be successful, postoperative edema might be minimized. Until then, a careful lymphatic-sparing dissection should be executed when performing a peripheral bypass reconstruction. Postoperatively, the use of compression stockings and leg elevation are currently the golden standards.
Crossover ilio-iliac bypass and removal of femoro-femoral graft as first treatment for the infection of crossover bypass in aortouniiliac endovascular aneurysm repair
Authors: Bonardelli Stefano , Nodari Franco , De Lucia Maurizio , Cervi Edoardo , Giulini Stefano Maria
Published: March 2013

The crossover femoro-femoral bypass, classically used for the treatment of unilateral iliac arterial obstruction, has recently become an integral part of aortouniiliac endovascular aneurysm repair. We therefore, reconsider the therapeutic problems related to thrombosis and in particular to infection of the femoro-femoral prosthesis, when many attempts have been made to preserve the bypass and treat the infection. Showing a case treated and well eight months later, we put forward the old technique of crossover ilio-iliac bypass, followed by the removal of the infected femoro-femoral graft. In our opinion, this technique circumvents the need for autologous tissue and allows for the use of prosthetics in a new, sterile, uncontaminated field. As this approach for these cases has so far not been reported in the literature, further cases and long-term follow-up are needed.
Molecular data analysis of selected housekeeping and informational genes from nineteen Campylobacter jejuni genomes
Authors: Mohan Vathsala , Stevenson Mark
Published: March 2013

Campylobacter jejuni (C. jejuni) is a rapidly evolving bacterial species with massive genetic recombination potential to generate niche specific genotypes. Generally the housekeeping gene lineage has been evidenced to undergo lateral gene transfer and recombination fairly frequently compared to the information processing gene lineage. During such exchanges, gene amelioration takes place over time acquiring the host genomes’ molecular characteristics. In this study fifty genes that comprised twenty five housekeeping lineage genes and twenty five information processing lineage genes from nineteen C. jejuni genomes were studied. These nineteen genomes included seven C. jejuni isolates that belonged to the same genotype or multilocus sequence type ST-474. The genes from both lineages were tested for recombination and the guanine-cytosine (GC) variation. This paper details about the data collected and the analyses performed in the corresponding research article entitled ”Campylobacter jejuni genomes exhibit notable GC variation within housekeeping genes”. Further, this paper provides details on the results that are not included in the research paper to provide completeness to the study conducted. The gene sequences from the seven C. jejuni ST-474 isolates were submitted to the GenBank and the corresponding gene IDs are provided for referencing purposes.
Foundations for Group Decision Analysis
Authors: Keeney Ralph L.
Published: March 2013

This paper derives a general prescriptive model for group decision analysis based on a set of logical and operational assumptions analogous to those for individual decision analysis. The approach accounts for each group member's potentially different frames of their common decision, including different events and different consequences of concern. Assuming that each group member accepts the decision analysis assumptions to evaluate his or her analysis of what the group should do and that the group accepts an analogous set of decision analysis assumptions for the group's decision, it is proven that the group expected utility for an alternative should be a weighted sum of the individual member's expected utilities for the alternatives. After each group member does his or her decision analysis of the group's alternatives, the essence of the group decision analysis is to specify the weights based on the interpersonal comparison of utilities and on the relative importance or power of each individual in the group.