bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive phylogeny of apid bees reveals the evolutionary origins and antiquity of cleptoparasitism
Authors: Cardinal Sophie , Straka Jakub , Danforth Bryan N.
Published: August 2010

Apidae is the most speciose and behaviorally diverse family of bees. It includes solitary, eusocial, socially parasitic, and an exceptionally high proportion of cleptoparasitic species. Cleptoparasitic bees, which are brood parasites in the nests of other bees, have long caused problems in resolving the phylogenetic relationships within Apidae based on morphological data because of the tendency for parasites to converge on a suite of traits, making it difficult to differentiate similarity caused by common ancestry from convergence. Here, we resolve the evolutionary history of apid cleptoparasitism by conducting a detailed, comprehensive molecular phylogenetic analysis of all 33 apid tribes (based on 190 species), including representatives from every hypothesized origin of cleptoparasitism. Based on Bayesian ancestral state reconstruction, we show that cleptoparasitism has arisen just four times in Apidae, which is fewer times than previously estimated. Our results indicate that 99% of cleptoparasitic apid bees form a monophyletic group. Divergence time estimates reveal that cleptoparasitism is an ancient behavior in bees that first evolved in the late Cretaceous 95 Mya [95% highest posterior density (HPD) = 87–103]. Our phylogenetic analysis of the Apidae sheds light on the macroevolution of a bee family that is of evolutionary, ecological, and economic importance.
Ancient pinnate leaf mimesis among lacewings
Authors: Wang Yongjie , Liu Zhiqi , Wang Xin , Shih Chungkun , Zhao Yunyun , Engel Michael S. , Ren Dong
Published: August 2010

Insects have evolved diverse methods of predator avoidance, many of which implicate complex adaptations of their wings (e.g., Phylliidae, Nymphalidae, Notodontidae). Among these, angiosperm leaf mimicry is one of the most dramatic, although the historical origins of such modifications are unclear owing to a dearth of paleontological records. Here, we report evidence of pinnate leaf mimesis in two lacewings (Neuroptera):
Bellinympha filicifolia
Y. Wang, Ren, Liu & Engel gen. et sp. nov. and
Bellinympha dancei
Y. Wang, Ren, Shih & Engel, sp. nov., from the Middle Jurassic, representing a 165-million-year-old specialization between insects and contemporaneous gymnosperms of the Cycadales or Bennettitales. Furthermore, such lacewings demonstrate a preangiosperm origin for leaf mimesis, revealing a lost evolutionary scenario of interactions between insects and gymnosperms. The current fossil record suggests that this enigmatic lineage became extinct during the Early Cretaceous, apparently closely correlated with the decline of Cycadales and Bennettitales at that time, and perhaps owing to the changing floral environment resulted from the rise of flowering plants.
Imaging mass spectrometry of intraspecies metabolic exchange revealed the cannibalistic factors of
Bacillus subtilis
Authors: Liu Wei-Ting , Yang Yu-Liang , Xu Yuquan , Lamsa Anne , Haste Nina M. , Yang Jane Y. , Ng Julio , Gonzalez David , Ellermeier Craig D. , Straight Paul D. , Pevzner Pavel A. , Pogliano Joe , Nizet Victor , Pogliano Kit , Dorrestein Pieter C.
Published: August 2010

During bacterial cannibalism, a differentiated subpopulation harvests nutrients from their genetically identical siblings to allow continued growth in nutrient-limited conditions. Hypothesis-driven imaging mass spectrometry (IMS) was used to identify metabolites active in a
Bacillus subtilis
cannibalism system in which sporulating cells lyse nonsporulating siblings. Two candidate molecules with sequences matching the products of
skfA
and
sdpC
, genes for the proposed cannibalistic factors sporulation killing factor (SKF) and sporulation delaying protein (SDP), respectively, were identified and the structures of the final products elucidated. SKF is a cyclic 26-amino acid (aa) peptide that is posttranslationally modified with one disulfide and one cysteine thioether bridged to the α-position of a methionine, a posttranslational modification not previously described in biology. SDP is a 42-residue peptide with one disulfide bridge. In spot test assays on solid medium, overproduced SKF and SDP enact a cannibalistic killing effect with SDP having higher potency. However, only purified SDP affected
B. subtilis
cells in liquid media in fluorescence microscopy and growth assays. Specifically, SDP treatment delayed growth in a concentration-dependent manner, caused increases in cell permeability, and ultimately caused cell lysis accompanied by the production of membrane tubules and spheres. Similarly, SDP but not SKF was able to inhibit the growth of the pathogens
Staphylococcus aureus
and
Staphylococcus epidermidis
with comparable IC
50
to vancomycin. This investigation, with the identification of SKF and SDP structures, highlights the strength of IMS in investigations of metabolic exchange of microbial colonies and also demonstrates IMS as a promising approach to discover novel biologically active molecules.
Oil sands development contributes elements toxic at low concentrations to the Athabasca River and its tributaries
Authors: Kelly Erin N. , Schindler David W. , Hodson Peter V. , Short Jeffrey W. , Radmanovich Roseanna , Nielsen Charlene C.
Published: August 2010

We show that the oil sands industry releases the 13 elements considered priority pollutants (PPE) under the US Environmental Protection Agency's Clean Water Act, via air and water, to the Athabasca River and its watershed. In the 2008 snowpack, all PPE except selenium were greater near oil sands developments than at more remote sites. Bitumen upgraders and local oil sands development were sources of airborne emissions. Concentrations of mercury, nickel, and thallium in winter and all 13 PPE in summer were greater in tributaries with watersheds more disturbed by development than in less disturbed watersheds. In the Athabasca River during summer, concentrations of all PPE were greater near developed areas than upstream of development. At sites downstream of development and within the Athabasca Delta, concentrations of all PPE except beryllium and selenium remained greater than upstream of development. Concentrations of some PPE at one location in Lake Athabasca near Fort Chipewyan were also greater than concentration in the Athabasca River upstream of development. Canada's or Alberta's guidelines for the protection of aquatic life were exceeded for seven PPE—cadmium, copper, lead, mercury, nickel, silver, and zinc—in melted snow and/or water collected near or downstream of development.
Endosomal-sorting complexes required for transport (ESCRT) pathway-dependent endosomal traffic regulates the localization of active Src at focal adhesions
Authors: Tu Chun , Ortega-Cava Cesar F. , Winograd Paul , Stanton Marissa Jo , Reddi Alagarsamy Lakku , Dodge Ingrid , Arya Ranjana , Dimri Manjari , Clubb Robert J. , Naramura Mayumi , Wagner Kay-Uwe , Band Vimla , Band Hamid
Published: August 2010

Active Src localization at focal adhesions (FAs) is essential for cell migration. How this pool is linked mechanistically to the large pool of Src at late endosomes (LEs)/lysosomes (LY) is not well understood. Here, we used inducible
Tsg101
gene deletion, TSG101 knockdown, and dominant-negative VPS4 expression to demonstrate that the localization of activated cellular Src and viral Src at FAs requires the endosomal-sorting complexes required for transport (ESCRT) pathway.
Tsg101
deletion also led to impaired Src-dependent activation of STAT3 and focal adhesion kinase and reduced cell migration. Impairment of the ESCRT pathway or Rab7 function led to the accumulation of active Src at aberrant LE/LY compartments followed by its loss. Analyses using fluorescence recovery after photo-bleaching show that dynamic mobility of Src in endosomes is ESCRT pathway-dependent. These results reveal a critical role for an ESCRT pathway-dependent LE/LY trafficking step in Src function by promoting localization of active Src to FAs.
Identification of differential and functionally active miRNAs in both anaplastic lymphoma kinase (ALK)+and ALK−anaplastic large-cell lymphoma
Authors: Merkel Olaf , Hamacher Frank , Laimer Daniela , Sifft Eveline , Trajanoski Zlatko , Scheideler Marcel , Egger Gerda , Hassler Melanie R. , Thallinger Christiane , Schmatz Ana , Turner Suzanne D. , Greil Richard , Kenner Lukas
Published: August 2010

Aberrant anaplastic lymphoma kinase (ALK) expression is a defining feature of many human cancers and was identified first in anaplastic large-cell lymphoma (ALCL), an aggressive non-Hodgkin T-cell lymphoma. Since that time, many studies have set out to identify the mechanisms used by aberrant ALK toward tumorigenesis. We have identified a distinct profile of micro-RNAs (miRNAs) that characterize ALCL; furthermore, this profile distinguishes ALK+from ALK−subtypes, and thus points toward potential mechanisms of tumorigenesis induced by aberrant ALK. Using a nucleophosmin-ALK transgenic mouse model as well as human primary ALCL tumor tissues and human ALCL-derived cell lines, we reveal a set of overlapping deregulated miRNAs that might be implicated in the development and progression of ALCL. Importantly, ALK+and ALK−ALCL could be distinguished by a distinct profile of “oncomirs”: Five members of the miR-17–92 cluster were expressed more highly in ALK+ALCL, whereas miR-155 was expressed more than 10-fold higher in ALK−ALCL. Moreover, miR-101 was down-regulated in all ALCL model systems, but its forced expression attenuated cell proliferation only in ALK+and not in ALK−cell lines, perhaps suggesting different modes of ALK-dependent regulation of its target proteins. Furthermore, inhibition of mTOR, which is targeted by miR-101, led to reduced tumor growth in engrafted ALCL mouse models. In addition to future therapeutical and diagnostic applications, it will be of interest to study the physiological implications and prognostic value of the identified miRNA profiles.
Microbial community transcriptomes reveal microbes and metabolic pathways associated with dissolved organic matter turnover in the sea
Authors: McCarren Jay , Becker Jamie W. , Repeta Daniel J. , Shi Yanmei , Young Curtis R. , Malmstrom Rex R. , Chisholm Sallie W. , DeLong Edward F.
Published: August 2010

Marine dissolved organic matter (DOM) contains as much carbon as the Earth's atmosphere, and represents a critical component of the global carbon cycle. To better define microbial processes and activities associated with marine DOM cycling, we analyzed genomic and transcriptional responses of microbial communities to high-molecular-weight DOM (HMWDOM) addition. The cell density in the unamended control remained constant, with very few transcript categories exhibiting significant differences over time. In contrast, the DOM-amended microcosm doubled in cell numbers over 27 h, and a variety of HMWDOM-stimulated transcripts from different taxa were observed at all time points measured relative to the control. Transcripts significantly enriched in the HMWDOM treatment included those associated with two-component sensor systems, phosphate and nitrogen assimilation, chemotaxis, and motility. Transcripts from
Idiomarina
and
Alteromonas
spp., the most highly represented taxa at the early time points, included those encoding TonB-associated transporters, nitrogen assimilation genes, fatty acid catabolism genes, and TCA cycle enzymes. At the final time point,
Methylophaga
rRNA and non-rRNA transcripts dominated the HMWDOM-amended microcosm, and included gene transcripts associated with both assimilatory and dissimilatory single-carbon compound utilization. The data indicated specific resource partitioning of DOM by different bacterial species, which results in a temporal succession of taxa, metabolic pathways, and chemical transformations associated with HMWDOM turnover. These findings suggest that coordinated, cooperative activities of a variety of bacterial “specialists” may be critical in the cycling of marine DOM, emphasizing the importance of microbial community dynamics in the global carbon cycle.
Proline-rich tyrosine kinase-2 is critical for CD8 T-cell short-lived effector fate
Authors: Beinke Sören , Phee Hyewon , Clingan Jonathan M. , Schlessinger Joseph , Matloubian Mehrdad , Weiss Arthur
Published: August 2010

T-cell interactions with antigen-presenting cells are important for CD8 T-cell effector or memory fate determination. The integrin leukocyte function-associated antigen-1 (LFA-1) mediates T-cell adhesion but the contribution of LFA-1–induced signaling pathways to T-cell responses is poorly understood. Here we demonstrate that proline-rich tyrosine kinase-2 (PYK2) deficiency impairs CD8 T-cell activation by synergistic LFA-1 and T-cell receptor stimulation. Furthermore, PYK2 is essential for LFA-1-mediated CD8 T-cell adhesion and LFA-1 costimulation of CD8 T-cell migration. During lymphocytic choriomeningitis virus infection in vivo, PYK2 deficiency results in a specific loss of short-lived effector CD8 T cells but does not affect memory-precursor CD8 T-cell development. Similarly, lack of LFA-1 primarily impairs the generation of short-lived effector cells. Thus, PYK2 facilitates LFA-1–dependent CD8 T-cell responses and promotes CD8 T-cell short-lived effector fate, suggesting that PYK2 may be an interesting therapeutic target to suppress exacerbated CD8 T-cell responses.
Focal Müllerian duct retention in male mice with constitutively activated β-catenin expression in the Müllerian duct mesenchyme
Authors: Tanwar Pradeep S. , Zhang LiHua , Tanaka Yoshihiro , Taketo Makoto M. , Donahoe Patricia K. , Teixeira Jose M.
Published: August 2010

Müllerian-inhibiting substance (MIS), which is produced by fetal Sertoli cells shortly after commitment of the bipotential gonads to testicular differentiation, causes Müllerian duct (MD) regression. In the fetal female gonads, MIS is not expressed and the MDs will differentiate into the internal female reproductive tract. We have investigated whether dysregulated β-catenin activity affects MD regression by expressing a constitutively activated nuclear form of β-catenin in the MD mesenchyme. We show that constitutively activated (CA) β-catenin causes focal retention of MD tissue in the epididymides and vasa deferentia. In adult mutant mice, the retained MD tissues express α-smooth muscle actin and desmin, which are markers for uterine differentiation. MD retention inhibited the folding complexity of the developing epididymides and usually led to obstructive azoospermia by spermatoceles. The MDs of urogenital ridges from mutant female embryos showed less regression with added MIS in organ culture compared with control MDs when analyzed by whole mount in situ hybridization for Wnt7a as a marker for the MD epithelium. CA β-catenin did not appear to affect expression of either MIS in the embryonic testes or its type II receptor (AMHR2) in the MD mesenchyme nor did it inhibit pSmad1/5/8 nuclear accumulation, suggesting that dysregulated β-catenin must inhibit MD regression independently of MIS signaling. These studies suggest that dysregulated Wnt/β-catenin signaling in the MD mesenchyme might also be a contributing factor in persistent Müllerian duct syndrome, a form of male pseudohermaphroditism, and development of spermatoceles.
Multipotential hematopoietic blast colony-forming cells exhibit delays in self-generation and lineage commitment
Authors: Metcalf Donald , Ng Ashley , Mifsud Sandra , Di Rago Ladina
Published: August 2010

Murine hematopoietic blast colony-forming cells (BL-CFCs) are able to generate up to 30,000 progeny blast cells within 10 d in agar cultures. Contained in these populations are large numbers of lineage-committed progenitor cells in the granulocytic and macrophage lineages. Sequential analyses of blast colonies revealed that self-generation of BL-CFCs occurs but is surprisingly late in clonal expansion, as is the emergence of progenitor cells committed to megakaryocytic and eosinophil lineages. Self-generating BL-CFCs were highly enriched in lineage
−
Kit
+
Sca1
+
CD34
−
Flt3R
−
populations, and colonies generated by such cells contained colony-forming units–spleen and formed erythroid and lymphoid progeny in vivo. The data suggest the existence of a hierarchical structure in BL-CFC populations with at least a subset being cells assayable as colony-forming units–spleen. Because BL-CFCs can self-generate and are able to generate lymphoid and myeloid populations, BL-CFCs appear to be ideal cells in which to analyze the processes of self-generation and lineage commitment in clonal in vitro cultures.
Teaching mindfulness to psychotherapists in clinical practice: The Mindful Therapy Programme
Authors: Aggs Cameron , Bambling Matthew
Published: August 2010

Introduction: Initially proposed as a treatment modality for psychological disorders, mindfulness is now being promoted as a means of enhancing both therapist self care and therapeutic efficacy. The degree to which mindfulness can be learned by therapists to manage their own and clients' processes in therapy is as yet unknown. This study examines training outcomes of a standardised introductory mindfulness programme for mental health professionals. Methods: Forty‐seven mental health professionals completed an eight‐week mindful therapy (MT) training programme and associated measures. Results: Compared with baseline scores, participants demonstrated knowledge acquisition on all measures, including increased mindfulness in clinical work, increased capacity to intentionally invoke mindful states of consciousness, and higher participant ratings of well‐being over the course of training sessions. Discussion: This research provides preliminary evidence that a brief, standardised mindfulness training programme can achieve acceptable knowledge and skills outcomes for therapists that can aid their therapeutic practice. Of note, increased ‘therapeutic mindfulness’ in this study resulted from changed mindfulness ‘attitudes’ (i.e. a more accepting and equanimous orientation within therapeutic work) as opposed to a clear demonstration of increased attention‐regulation skills. The implications of these and other results for programme development and wider research are discussed.
Two distinct mechanisms target GAD67 to vesicular pathways and presynaptic clusters
Authors: Kanaani Jamil , Kolibachuk Julia , Martinez Hugo , Baekkeskov Steinunn
Published: August 2010

The inhibitory neurotransmitter γ-amino butyric acid (GABA) is synthesized by two isoforms of the enzyme glutamic acid decarboxylase (GAD): GAD65 and GAD67. Whereas GAD67 is constitutively active and produces >90% of GABA in the central nervous system, GAD65 is transiently activated and augments GABA levels for rapid modulation of inhibitory neurotransmission. Hydrophobic lipid modifications of the GAD65 protein target it to Golgi membranes and synaptic vesicles in neuroendocrine cells. In contrast, the GAD67 protein remains hydrophilic but has been shown to acquire membrane association by heterodimerization with GAD65. Here, we identify a second mechanism that mediates robust membrane anchoring, axonal targeting, and presynaptic clustering of GAD67 but that is independent of GAD65. This mechanism is abolished by a leucine-103 to proline mutation that changes the conformation of the N-terminal domain but does not affect the GAD65-dependent membrane anchoring of GAD67. Thus two distinct mechanisms target the constitutively active GAD67 to presynaptic clusters to facilitate accumulation of GABA for rapid delivery into synapses.
The NuRD chromatin–remodeling complex regulates signaling and repair of DNA damage
Authors: Smeenk Godelieve , Wiegant Wouter W. , Vrolijk Hans , Solari Aldo P. , Pastink Albert , van Attikum Haico
Published: August 2010

Cells respond to ionizing radiation (IR)–induced DNA double-strand breaks (DSBs) by orchestrating events that coordinate cell cycle progression and DNA repair. How cells signal and repair DSBs is not yet fully understood. A genome-wide RNA interference screen in Caenorhabditis elegans identified egr-1 as a factor that protects worm cells against IR. The human homologue of egr-1, MTA2 (metastasis-associated protein 2), is a subunit of the nucleosome-remodeling and histone deacetylation (NuRD) chromatin-remodeling complex. We show that knockdown of MTA2 and CHD4 (chromodomain helicase DNA-binding protein 4), the catalytic subunit (adenosine triphosphatase [ATPase]) of NuRD, leads to accumulation of spontaneous DNA damage and increased IR sensitivity. MTA2 and CHD4 accumulate in DSB-containing chromatin tracks generated by laser microirradiation. Directly at DSBs, CHD4 stimulates RNF8/RNF168-dependent formation of ubiquitin conjugates to facilitate the accrual of RNF168 and BRCA1. Finally, we show that CHD4 promotes DSB repair and checkpoint activation in response to IR. Thus, the NuRD chromatin–remodeling complex is a novel regulator of DNA damage responses that orchestrates proper signaling and repair of DSBs.
The mitosis-to-interphase transition is coordinated by cross talk between the SIN and MOR pathways in Schizosaccharomyces pombe
Authors: Ray Samriddha , Kume Kazunori , Gupta Sneha , Ge Wanzhong , Balasubramanian Mohan , Hirata Dai , McCollum Dannel
Published: August 2010

The mechanisms that regulate cytoskeletal remodeling during the transition between mitosis and interphase are poorly understood. In fission yeast the MOR pathway promotes actin polarization to cell tips in interphase, whereas the SIN signaling pathway drives actomyosin ring assembly and cytokinesis. We show that the SIN inhibits MOR signaling in mitosis by interfering with Nak1 kinase-mediated activation of the most downstream MOR component, the NDR family kinase Orb6. Inactivation of the MOR may be a key function of the SIN because attenuation of MOR signaling rescued the cytokinetic defects of SIN mutants and allowed weak SIN signaling to trigger ectopic cytokinesis. Furthermore, failure to inhibit the MOR is toxic when the cell division apparatus is compromised. Together, our results reveal a mutually antagonistic relationship between the SIN and MOR pathways, which is important for completion of cytokinesis and coordination of cytoskeletal remodeling at the mitosis-to-interphase transition.
Reduction of Seasonal Influenza Transmission among Healthcare Workers in an Intensive Care Unit: A 4-Year Intervention Study in Thailand
Authors: Apisarnthanarak Anucha , Uyeki Timothy M. , Puthavathana Pilaipan , Kitphati Rungrueng , Mundy Linda M.
Published: August 2010

Objective.

To evaluate the feasibility and effectiveness of an influenza control bundle to minimize healthcare-associated seasonal influenza transmission among healthcare workers (HCWs) in an intensive care unit (ICU) equipped with central air conditioning.

Methods.

A quasi-experimental study was conducted in a 500-bed tertiary care center in Thailand from July 1, 2005, through June 30, 2009. The medical ICU (MICU) implemented an influenza control bundle including healthcare worker (HCW) education, influenza screening of adult community-acquired pneumonia patients, antiviral treatment of patients and ill HCWs who tested positive for influenza, promotion of influenza vaccination among HCWs, and reinforcement of standard infection control policies. The surgical ICU (SICU) and coronary care unit (CCU) received no intervention.

Results.

The numbers of influenza infections among HCWs during the pre- and postintervention periods were 18 cases in 5,294 HCW-days and 0 cases in 5,336 HCW-days in the MICU (3.4 vs 0 cases per 1,000 HCW-days; P < .001), 19 cases in 4,318 HCW-days and 20 cases in 4,348 HCW-days in the SICU (4.4 vs 4.6 cases per 1,000 HCW-days; P = .80), and 18 cases in 5,000 HCW-days and 18 cases in 5,143 HCW-days in the CCU (3.6 vs 3.5 cases per 1,000 HCW-days; P = .92), respectively. Outbreak-related influenza occurred in 7 MICU HCWs, 6 SICU HCWs, and 4 CCU HCWs before intervention and 0 MICU HCWs, 9 SICU HCWs, and 8 CCU HCWs after intervention. Before and after intervention, 25 (71%) and 35 (100%) of 35 MICU HCWs were vaccinated, respectively (P < .001); HCW vaccination coverage did not change significantly in the SICU (21 [70%] of 30 vs 24 [80%] of 30; P = .89) and CCU (19 [68%] of 28 vs 21 [75%] of 28; P = .83). The estimated costs of US $6,471 per unit for postintervention outbreak investigations exceeded the intervention costs of US $4,969.

Conclusion.

A sustained influenza intervention bundle was associated with clinical and economic benefits to a Thai hospital.
Lyric Economies: Manufacturing Values in French Petrarchan Collections (1549–60)*
Authors: Alduy Cécile
Published: August 2010

Between 1549 and 1560, French Petrarchan sonnet sequences proliferated in the wake of Du Bellay'sDefense and Illustration of the French Tongueand Ronsard'sAmours. Yet this proliferation relied on a remarkable economy of means, in large part due to the constant recycling of metaphors, tropes, and forms. In fact, the genre can be read as a cost-efficient system that addressed the economic anxiety of a generation of poets caught between the aspiration to impose the autonomy of their art and their social dependence on a patron. It also preemptively solved the potential credit crisis that could have resulted from having had to borrow from the Italians in order to establish a new French canon. Looking at Ronsard, Du Bellay, and Ellain, this essay examines French Petrarchan collections as complex lyric economies that manufacture and negotiate aesthetic, literary, monetary, and national values.
Acute Anemia Elicits Cognitive Dysfunction and Evidence of Cerebral Cellular Hypoxia in Older Rats with Systemic Hypertension
Authors: Li Min , Bertout Jessica A. , Ratcliffe Sarah J. , Eckenhoff Maryellen F. , Simon M. Celeste , Floyd Thomas F.
Published: August 2010

Background

Postoperative cognitive dysfunction occurs frequently after cardiac, major vascular, and major orthopedic surgery. Aging and hypertensive cerebrovascular disease are leading risk factors for this disorder. Acute anemia, common to major surgery, has been identified as a possible contributor to postoperative cognitive dysfunction. The effect of hypoxia upon cognition and the cellular and molecular processes involved in learning and memory has been well described. Cerebrovascular changes related to chronic hypertension may expose cells to increased hypoxia with anemia.

Methods

Young to aged spontaneously hypertensive rats underwent testing for visuospatial memory and learning in the Morris water maze, measurement of cerebral tissue oxygenation via tissue oxygen probe, and measurement of hypoxia-sensitive genes and proteins, under conditions of sham and experimental isovolemic anemia.

Results

Acute isovolemic anemia elicited evidence of aging-dependent visuospatial working memory and learning impairment. Isovolemic anemia did not result in cerebral tissue hypoxia, when measured via tissue oxygen probe. Evidence of cellular hypoxia was, however, identified in response to the anemic challenge, as hypoxia-sensitive genes and proteins were up-regulated. Importantly, cellular hypoxic gene responses were increased with anemia in an age-dependent manner in this model of aging with chronic hypertension.

Conclusions

In a translational model of chronic hypertension, clinically relevant levels of acute anemia were associated with an age-dependent visuospatial working memory and learning impairment that was matched by an age-dependent cellular sensitivity to anemic hypoxia. These data offer support for a possible link between anemic hypoxia and postoperative cognitive dysfunction in humans.
Prediction of Pediatric Endotracheal Tube Size by Ultrasonography
Authors: Shibasaki Masayuki , Nakajima Yasufumi , Ishii Sachiyo , Shimizu Fumihiro , Shime Nobuaki , Sessler Daniel I.
Published: August 2010

Background

Formulas based on age and height often fail to reliably predict the proper endotracheal tube (ETT) size in pediatric patients. We, thus, tested the hypothesis that subglottic diameter, as determined by ultrasonography, better predicts optimal ETT size than existing methods.

Methods

A total of 192 patients, aged 1 month to 6 yr, who were scheduled for surgery and undergoing general anesthesia were enrolled and divided into development and validation phases. In the development group, the optimal ETT size was selected according to standard age-based formulas for cuffed and uncuffed tubes. Tubes were replaced as necessary until a good clinical fit was obtained. Via ultrasonography, the subglottic upper airway diameter was determined before tracheal intubation. We constructed a regression equation between the subglottic upper airway diameter and the outer diameter of the ETT finally selected. In the validation group, ETT size was selected after ultrasonography using this regression equation. The primary outcome was the fraction of initial cuffed and uncuffed tube sizes, as selected through the regression formula, that proved clinically optimal.

Results

Subglottic upper airway diameter was highly correlated with outer ETT diameter deemed optimal on clinical grounds. The rate of agreement between the predicted ETT size based on ultrasonic measurement and the final ETT size selected clinically was 98% for cuffed ETTs and 96% for uncuffed ETTs.

Conclusions

Measuring subglottic airway diameter with ultrasonography facilitates the selection of appropriately sized ETTs in pediatric patients. This selection method better predicted optimal outer ETT diameter than standard age- and height-based formulas.
Modeling the Effect of Sevoflurane on Corrected QT Prolongation
Authors: Han Dong Woo , Park Kyungsoo , Jang Seong Bok , Kern Steven E.
Published: August 2010

Background

Sevoflurane may prolong the corrected QT (QTc) interval in healthy humans when administered for induction and maintenance of anesthesia. Little information is available about the dose-response relationship of sevoflurane on the QTc interval. We performed a pharmacodynamic analysis of the relationship between end-tidal sevoflurane concentration (CET) and the QTc.

Methods

Twenty-one patients aged 20-50 yr were enrolled in this study. Sevoflurane concentrations were progressively increased and then decreased over 15 min at the start of anesthesia; CET and automated QT interval were recorded continuously. Pharmacodynamic analysis using a sigmoid Emax model was performed to assess the concentration-effect relationship.

Results

Maximal CET was 4.30 ± 0.33%. Measured baseline and maximally prolonged QTc interval values were 351.7 ± 15.4 ms and 397.8 ± 17.5 ms, respectively. During sevoflurane anesthesia, increased concentrations were correlated with prolonged QTc interval. Hysteresis between the CET and QTc interval were observed and accounted for in the model. Ce50 and ke0 were 2.5 ± 1.4 and 2.0 ± 1.0, respectively. The median prediction error, median absolute prediction error, and the coefficient of determination (R) were 0.02%, 0.75%, and 0.95, respectively. The effect-site concentration (Ce50) and QTc interval data fit to a sigmoid Emax model.

Conclusions

Among patients receiving sevoflurane for anesthesia, QTc interval changes correlate to anesthetic level. The Ce50 for significant QTc change is at clinically relevant levels of sevoflurane anesthesia.
Familial Adenomatous Polyposis in Children and Adolescents
Authors: Alkhouri Naim , Franciosi James P , Mamula Petar
Published: August 2010

Background:

Familial adenomatous polyposis (FAP) is the most common inherited polyposis syndrome characterized by the development of hundreds of colorectal adenomatous polyps. The aim of this study was to review cases of FAP diagnosed at The Children's Hospital of Philadelphia in a 16‐year period.

Methods:

Medical records of patients diagnosed as having FAP between 1990 and 2005 were reviewed. The collected data included disease presentation, genetic profile, extraintestinal manifestations, surveillance, and treatment.

Results:

We identified 12 patients with FAP. The age range at presentation was 7 to 18 years. Seven (68%) patients presented due to symptoms, the most common of which was rectal bleeding (6 patients, 86%). The youngest age at which polyps were detected was 7 years. Eight patients (67%) had positive family history. Three patients had Gardner syndrome and 1 presented in infancy with hepatoblastoma. Four patients had adenomatous polyposis coli gene mutation identified. One patient was diagnosed as having rectal carcinoma in situ. Six patients (50%) had gastric fundic gland polyposis and 6 had duodenal adenomatous changes. Capsule endoscopy was performed in 3 patients; 1 had multiple polyps in the duodenum and the jejunum. Seven patients (58%) underwent total colectomy with no serious complications.

Conclusions:

FAP is a rare condition but with significant risk of cancer and comorbidity. In this series, patients commonly presented to medical attention due to their symptoms. The youngest patient with polyps detected was 7 years old. We identified 1 patient with rectal cancer in situ and high proportion of patients with duodenal adenomatous lesions. Majority of patients underwent early colectomy.
Evaluation of the Quality of Guidelines for Acute Gastroenteritis in Children With the AGREE Instrument
Authors: Lo Vecchio Andrea , Giannattasio Antonietta , Duggan Christopher , De Masi Salvatore , Ortisi Maria Teresa , Parola Luciana , Guarino Alfredo
Published: August 2010

Aim:

The aim of the study was to assess the quality of clinical practice guidelines (CPGs) using the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument, a validated international tool.

Materials and Methods:

CPGs were identified by searching MEDLINE (1966–January 2009) and Embase (1988–January 2009), CPG databases, and relevant Web sites of agencies and organizations that produce and/or endorse guidelines. Included in the study were CPGs in English that addressed the management of acute gastroenteritis in children. Retrieved CPGs were evaluated with the AGREE instrument for quality assessment by 6 independent reviewers. AGREE consists of 6 domains for a total of 23 items.

Results:

Nine CPGs were identified. Four were evidence based (EB) and 2 of these included tables of evidence. Eight CPGs (88%) scored <50% for “applicability,” 7 (77%) for “stakeholder involvement,” and 6 (66%) for “editorial independence.” Compared with non‐EB CPGs, EB CPGs had higher quality scores for all AGREE domains, with a better score for “rigor of development” (P < 0.001), “stakeholder involvement” and “clarity of presentation” (P < 0.01), and applicability (P < 0.05). Over time, the quality of guidelines tended to improve. The main recommendations of CPGs were similar. However, there were differences in the treatment of diarrhea, namely based on the settings and circumstances in which CPGs were produced.

Conclusions:

The overall quality of CPGs on acute gastroenteritis management in children is fair. Aims, target population, synthesis of evidence, formulation of recommendations, and clarity of presentation are points of strength. Weak issues are applicability, including identification of organizational barriers and adherence parameters, and cost/efficacy analysis.
Maintenance Treatment With Proton Pump Inhibitors for Reflux Esophagitis in Pediatric Patients: A Systematic Literature Analysis
Authors: Illueca Marta , Wernersson Börje , Henderson Catherine , Lundborg Per
Published: August 2010

Objectives:

Short‐term treatment with a proton pump inhibitor (PPI) is effective for healing reflux esophagitis and improving reflux symptoms in pediatric patients. Our aim was to assess the efficacy and tolerability of maintenance PPI treatment after healing of reflux esophagitis in pediatric patients.

Materials and Methods:

Systematic searches of MEDLINE, Excerpta Medica database, and recent conference abstracts.

Results:

Five studies evaluated the efficacy of PPI maintenance therapy (6‐ to 90‐month follow‐up) in pediatric patients after healing of reflux esophagitis. Three found no relapse of reflux esophagitis or reflux symptoms during PPI maintenance therapy; however, a low relapse rate (1/14) was also found in the placebo group of the only prospective controlled study. Two of the 5 studies (both prospective) reported relapse of reflux esophagitis at half the original healing dose of omeprazole (7 of 51 patients relapsed after 3 months; 8 of 32 within 21 months), which resolved again in most patients when the healing dose or higher was given. Four studies evaluated relapse of reflux esophagitis and/or reflux symptoms after stopping PPI therapy. Reflux symptoms recurred in 18% to 76% of patients across all 4 studies. In the 4 studies that assessed the safety of PPI maintenance therapy, adverse events were infrequent and of low severity.

Conclusions:

Pediatric patients with gastroesophageal reflux disease and certain chronic comorbidities appear to have the greatest need of maintenance PPI treatment after healing of reflux esophagitis. In patients requiring maintenance therapy, PPIs appear to be well tolerated and effective in maintaining remission of reflux esophagitis and reflux symptoms.
Arabidopsis Calcium-Dependent Protein Kinase CPK10 Functions in Abscisic Acid- and Ca2+-Mediated Stomatal Regulation in Response to Drought Stress
Authors: Zou Jun-Jie , Wei Feng-Ju , Wang Cun , Wu Juan-Juan , Ratnasekera Disna , Liu Wen-Xin , Wu Wei-Hua
Published: August 2010

Plant calcium-dependent protein kinases (CDPKs) may function as calcium sensors and play important roles in the regulation of plant growth and development and in plant responses to biotic and abiotic stresses. The Arabidopsis (Arabidopsis thaliana) genome encodes 34 CDPKs, and most of them have not been functionally characterized. Here, we report the functional characterization of CPK10 in Arabidopsis response to drought stress. The cpk10 mutant, a T-DNA insertion mutant for the Arabidopsis CPK10 gene, showed a much more sensitive phenotype to drought stress compared with wild-type plants, while the CPK10 overexpression lines displayed enhanced tolerance to drought stress. Induction of stomatal closure and inhibition of stomatal opening by abscisic acid (ABA) and Ca2+ were impaired in the cpk10 mutants. Using yeast two-hybrid methods, a heat shock protein, HSP1, was identified as a CPK10-interacting protein. The interaction between CPK10 and HSP1 was further confirmed by pull-down and bimolecular fluorescence complementation assays. The HSP1 knockout mutant (hsp1) plants showed a similar sensitive phenotype under drought stress as the cpk10 mutant plants and were similarly less sensitive to ABA and Ca2+ in regulation of stomatal movements. Electrophysiological experiments showed that ABA and Ca2+ inhibition of the inward K+ currents in stomatal guard cells were impaired in the cpk10 and hsp1 mutants. All presented data demonstrate that CPK10, possibly by interacting with HSP1, plays important roles in ABA- and Ca2+-mediated regulation of stomatal movements.
Mammalian cell expression, purification, crystallization and microcrystal data collection of autotaxin/ENPP2, a secreted mammalian glycoprotein
Authors: Hausmann Jens , Christodoulou Evangelos , Kasiem Mobien , De Marco Valeria , van Meeteren Laurens A. , Moolenaar Wouter H. , Axford Danny , Owen Robin L. , Evans Gwyndaf , Perrakis Anastassis
Published: August 2010

Autotaxin (ATX or ENPP2) is a secreted glycosylated mammalian enzyme that exhibits lysophospholipase D activity, hydrolyzing lysophosphatidylcholine to the signalling lipid lysophosphatidic acid. ATX is an ∼100 kDa multi-domain protein encompassing two N-terminal somatomedin B-like domains, a central catalytic phosphodiesterase domain and a C-terminal nuclease-like domain. Protocols for the efficient expression of ATX from stably transfected mammalian HEK293 cells in amounts sufficient for crystallographic studies are reported. Purification resulted in protein that crystallized readily, but various attempts to grow crystals suitable in size for routine crystallographic structure determination were not successful. However, the available micrometre-thick plates diffracted X-rays beyond 2.0 Å resolution and allowed the collection of complete diffraction data to about 2.6 Å resolution. The problems encountered and the current advantages and limitations of diffraction data collection from thin crystal plates are discussed.
Annual, lunar and diel reproductive periodicity of a spawning aggregation of snapper Pagrus auratus (Sparidae) in a marine embayment on the lower west coast of Australia
Authors: Wakefield C. B.
Published: August 2010

Ichthyoplankton sampling and ovarian characteristics were used to elucidate whether the reproductive cycles of a spawning aggregation of snapper Pagrus auratus in a nearshore marine embayment were temporally and spatially specific and related with environmental conditions. The reproductive dynamics of this aggregation were studied over four consecutive years (2001–2004). Spawning occurred between September and January each year, when water temperatures ranged from 15·8 to 23·1° C. In all 4 years, the cumulative egg densities in Cockburn Sound were highest when water temperatures were between the narrow range of 19–20° C. The spawning fraction of females was monthly bimodal and peaked during new and the full moons at 96–100% and c. 75%, respectively. The backcalculated ages of P. auratus eggs collected from 16 ichthyoplankton surveys demonstrated that P. auratus in Cockburn Sound spawn at night during the 3 h following the high tide. The spatial distributions of P. auratus eggs in Cockburn Sound during the peak reproductive period in all 4 years were consistent, further implying spawning was temporally and spatially specific. High concentrations of recently spawned eggs (8–16 h old) demonstrated spawning also occurred within the adjacent marine embayments of Owen Anchorage and Warnbro Sound. Water circulation in Cockburn and Warnbro Sounds resembled an eddy that was most prominent during the period of highest egg densities, thereby facilitating the retention of eggs in these areas. The reproductive cycles of P. auratus described in this study have assisted managers with the appropriate temporal and spatial scale for a closed fishing season to protect these spawning aggregations.
Vaccination with peptides derived from cancer‐testis antigens in combination with CpG‐7909 elicits strong specific CD8+ T cell response in patients with metastatic esophageal squamous cell carcinoma
Authors: Iwahashi Makoto , Katsuda Masahiro , Nakamori Mikihito , Nakamura Masaki , Naka Teiji , Ojima Toshiyasu , Iida Takeshi , Yamaue Hiroki
Published: August 2010

Potent helper action is necessary for peptide‐based vaccines to efficiently induce antitumor immune responses against advanced cancer. A phase I trial for advanced esophageal squamous cell carcinoma was carried out for patients with HLA‐A*2402 using epitope peptides derived from novel cancer‐testis antigens, LY6K and TTK, in combination with CpG‐7909 (NCT00669292). This study investigated the feasibility and the toxicity as well as induction of tumor antigen‐specific immune responses. Nine patients were vaccinated on days 1, 8, 15, and 22 of each 28‐day treatment cycle with peptide LY6K‐177, peptide TTK‐567, and CpG‐7909 (level‐1; 0, level‐2; 0.02, level‐3; 0.1 mg/kg) and all were tolerated by this treatment. LY6K‐specific T cell responses in PBMCs were detected in two of the three patients in each level. In particular, two patients in level‐2/3 showed potent LY6K‐specific T cell responses. In contrast, only two patients in level‐2/3 showed TTK‐567‐specific T cell responses. The frequency of LY6K‐177 or TTK‐567‐specific CD8+ T cells increased in patients in level‐2/3 (with CpG). The vaccination with peptides and CpG‐7909 increased and activated both plasmacytoid dentritic cells and natural killer cells, and increased the serum level of α‐interferon. There were no complete response (CR) and partial response (PR), however, one of three patients in level‐1, and four of six patients in level‐2/3 showed stable disease (SD). In conclusion, vaccination with LY6K‐177 and TTK‐567 in combination with CpG‐7909 successfully elicited antigen‐specific CD8+ T cell responses and enhanced the innate immunity of patients with advanced esophageal squamous cell carcinoma. This vaccine protocol is therefore recommended to undergo further phase II trials. (Cancer Sci 2010; 101: 2510–2517)
RNAi‐mediated CD73 suppression induces apoptosis and cell‐cycle arrest in human breast cancer cells
Authors: Zhi Xiuling , Wang Yingjian , Zhou Xuerui , Yu Jerry , Jian Rongrong , Tang Shaoxian , Yin Lianhua , Zhou Ping
Published: August 2010

Ecto‐5′‐nucleotidase (CD73), a cell surface protein that hydrolyzes extracellular AMP into adenosine and phosphate, is overexpressed in many solid tumors. In this study, we tested the hypothesis that increased CD73 may promote tumor progression by examining the effect of CD73 suppression via RNA interference and CD73 overexpression on tumor growth in vivo and in vitro. Using digitized whole‐body images, plate clone forming assay and TUNEL assay in frozen tissue sections, we found that the cell growth rate was significantly lower in vivo and in vitro after CD73 suppression and late apoptosis was much higher in xenograft tumors developed from the CD73‐siRNA transfected MB‐MDA‐231 clone (P1). By flow cytometry, the P1 cell cycle was arrested in the G0/G1 phase. Moreover, Bcl‐2 was downregulated, while Bax and caspase‐3 were upregulated with CD73 suppression. CD73 inhibitor α,β‐methylene adenosine‐5′‐disphosphate (APCP) functioned similarly with RNAi‐mediated CD73 suppression. In addition, in transfected MCF‐7 cells, we found that CD73 overexpression increased cell viability and promoted cell cycle progression, depending on its enzyme activity. More intriguingly, CD73 overexpression in MCF‐7 breast cancer cells produces a tumorigenic phenotype. We conclude that CD73 plays an important role in breast cancer growth by affecting cell cycle progression and apoptosis. (Cancer Sci 2010; 101: 2561–2569)