bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population genomic analysis uncovers African and European admixture in Drosophila melanogaster populations from the south‐eastern United States and Caribbean Islands
Authors: Kao Joyce Y. , Zubair Asif , Salomon Matthew P. , Nuzhdin Sergey V. , Campo Daniel 
Published: March 2015

AbstractDrosophila melanogaster is postulated to have colonized North America in the past several 100 years in two waves. Flies from Europe colonized the east coast United States while flies from Africa inhabited the Caribbean, which if true, make the south‐east US and Caribbean Islands a secondary contact zone for African and European D. melanogaster. This scenario has been proposed based on phenotypes and limited genetic data. In our study, we have sequenced individual whole genomes of flies from populations in the south‐east US and Caribbean Islands and examined these populations in conjunction with population sequences from the west coast US, Africa, and Europe. We find that west coast US populations are closely related to the European population, likely reflecting a rapid westward expansion upon first settlements into North America. We also find genomic evidence of African and European admixture in south‐east US and Caribbean populations, with a clinal pattern of decreasing proportions of African ancestry with higher latitude. Our genomic analysis of D. melanogaster populations from the south‐east US and Caribbean Islands provides more evidence for the Caribbean Islands as the source of previously reported novel African alleles found in other east coast US populations. We also find the border between the south‐east US and the Caribbean island to be the admixture hot zone where distinctly African‐like Caribbean flies become genomically more similar to European‐like south‐east US flies. Our findings have important implications for previous studies examining the generation of east coast US clines via selection.
The Pragmatics of Slurs
Authors: Bolinger Renée Jorgensen 
Published: March 2015

AbstractI argue that the offense generation pattern of slurring terms parallels that of impoliteness behaviors, and is best explained by appeal to similar purely pragmatic mechanisms. In choosing to use a slurring termratherthan its neutral counterpart, the speaker signals that she endorses the term (and its associations). Such an endorsement warrants offense, and consequently slurs generate offense whenever a speaker's use demonstrates a contrastive preference for the slurring term. Since this explanation comes at low theoretical cost and imposes few constraints on an account of the semantics of slurs, this suggests that we should not require semantic accounts to provide an independent explanation of the offense profile.
Herbert Rackow and Ernest Salanitre: the emergence of pediatric anesthesia as a specialty in the United States
Authors: Friesen Robert H. 
Published: March 2015

SummaryHerbert Rackow and Ernest Salanitre were pediatric anesthesiologists at Babies Hospital at the Columbia‐Presbyterian Medical Center in New York whose work spanned three decades beginning in the early 1950s. Their pioneering research included studies of the uptake and elimination of inhalational anesthetics and of the risk of cardiac arrest in infants and children. They were actively involved in the development of pediatric anesthesia as a specialty, and their efforts contributed to inter‐disciplinary collaboration and to the formation of the Section on Anesthesiology of the American Academy of Pediatrics. Their 1969 review article, ‘Modern Concepts in Pediatric Anesthesiology’, provides a fascinating view of pediatric anesthesia 50 years ago. In 1990, they were jointly awarded the Robert M. Smith award by the Section on Anesthesiology of the American Academy of Pediatrics.
Dexmedetomidine–ketamine combination and caudal block for superficial lower abdominal and genital surgery in children
Authors: Ibacache Mauricio E. , Muñoz Hernán R. , Fuentes Ricardo , Cortínez Luis I. 
Published: March 2015

SummaryBackgroundThe use of dexmedetomidine–ketamine combination to perform different diagnostic and surgical pediatric procedures has increased. The optimal ketamine dose to combine with dexmedetomidine has not been determined. The goal of this study was to determine the ED50 and ED95 of ketamine, which in combination with, dexmedetomidine (1 μg·kg−1) provides an adequate anesthetic effect to perform a caudal block and then the ensuing superficial lower abdominal or genital surgery.Material and MethodsTwenty‐five patients, aged 1–8 years, scheduled for superficial lower abdominal or genital surgery, were studied. All patients received an intravenous dose of dexmedetomidine 1 μg·kg−1 and a random dose of ketamine from 1 mg·kg−1 to 2 mg·kg−1. After ketamine administration, a caudal block was performed and then surgery was initiated. Hemodynamics, respiratory variables, sedation level, and postoperative complications were recorded. The ED50 and ED95 of ketamine were calculated using logistic regression analysis.ResultsThe ED50 and ED95 of ketamine to perform a caudal block were 1.53 (1.29–1.76) mg·kg−1 and 2.25 (1.63–2.88) mg·kg−1, respectively. The ED50 and ED95 of ketamine to perform a caudal block and to complete the entire procedure were 1.76 (1.57–1.95) mg·kg−1, and 2.21 (1.77–2.64) mg·kg−1, respectively. Three patients presented mild, self‐limited, intraoperative bradycardia.ConclusionsThese results suggest that adding ketamine 2 mg·kg−1 to dexmedetomidine 1 μg·kg−1 should produce an effective anesthetic level to perform a caudal block and the ensuing superficial lower abdominal or genital surgery in children.
Detoxification function of the Arabidopsis sulphotransferase AtSOT12 by sulphonation of xenobiotics
Authors: CHEN JINHUA , GAO LIQIONG , BAEK DONGWON , LIU CHUNLIN , RUAN YING , SHI HUAZHONG 
Published: March 2015

AbstractCytosolic sulphotransferases have been implicated in inactivation of endogenous steroid hormones and detoxification of xenobiotics in human and animals. Yet, the function of plant sulphotransferases in xenobiotic sulphonation and detoxification has not been reported. In this study, we show that the Arabidopsis sulphotransferase AtSOT12 could sulphonate the bacterial‐produced toxin cycloheximide. Loss‐of‐function mutant sot12 exhibited hypersensitive phenotype to cycloheximide, and expression of AtSOT12 protein in yeast cells conferred resistance to this toxic compound. AtSOT12 exhibited broad specificity and could sulphonate a variety of xenobiotics including phenolic and polycyclic compounds. Enzyme kinetics analysis indicated that AtSOT12 has different selectivity for simple phenolics with different side chains, and the position of the side chain in the simple phenolic compounds affects substrate binding affinity and catalytic efficiency. We proposed that the broad specificity and induced production of AtSOT12 may have rendered this enzyme to not only modify endogenous molecules such as salicylic acid as we previously reported, but also sulphonate pathogen‐produced toxic small molecules to protect them from infection. Sulphonation of small molecules in plants may constitute a rapid way to inactivate or change the physiochemical properties of biologically active molecules that could have profound effects on plant growth, development and defence.
Light‐harvesting superstructures of green plant chloroplasts lacking photosystems
Authors: Belgio Erica , Ungerer Petra , Ruban Alexander V. 
Published: March 2015

AbstractThe light‐harvesting antenna of higher plant photosystem II (LHCII) is the major photosynthetic membrane component encoded by an entire family of homologous nuclear genes. On the contrary, the great majority of proteins of photosystems and electron transport components are encoded by the chloroplast genome. In this work, we succeeded in gradually inhibiting the expression of the chloroplast genes that led to the disappearance of the photosystem complexes, mimicking almost total photoinhibition. The treated plants, despite displaying only some early signs of senescence, sustained their metabolism and growth for several weeks. The only major remaining membrane component was LHCII antenna that formed superstructures – stacks of dozens of thylakoids or supergrana. Freeze‐fracture electron microscopy revealed specific organization, directly displaying frequently bifurcated membranes with reduced or totally absent photosystem II (PSII) reaction centre complexes. Our findings show that it is possible to accumulate large amounts of light‐harvesting membranes, organized into three‐dimensional structures, in the absence of reaction centre complexes. This points to the reciprocal role of LHCII and PSII in self‐assembly of the three‐dimensional matrix of the photosynthetic membrane, dictating its size and flexible adaptation to the light environment.
Freezing avoidance by supercooling inOlea europaeacultivars: the role of apoplastic water, solute content and cell wall rigidity
Authors: Arias Nadia S. , Bucci Sandra J. , Scholz Fabian G. , Goldstein Guillermo 
Published: March 2015

AbstractPlants can avoid freezing damage by preventing extracellular ice formation below the equilibrium freezing temperature (supercooling). We usedOlea europaeacultivars to assess which traits contribute to avoid ice nucleation at sub‐zero temperatures. Seasonal leaf water relations, non‐structural carbohydrates, nitrogen and tissue damage and ice nucleation temperatures in different plant parts were determined in five cultivars growing in thePatagonian cold desert. Ice seeding in roots occurred at higher temperatures than in stems and leaves. Leaves of cold acclimated cultivars supercooled down to −13 °C, substantially lower than the minimum air temperatures observed in the study site. During winter, leaf ice nucleation and leaf freezing damage (LT50) occurred at similar temperatures, typical of plant tissues that supercool. Higher leaf density and cell wall rigidity were observed during winter, consistent with a substantial acclimation to sub‐zero temperatures. Larger supercooling capacity and lowerLT50were observed in cold‐acclimated cultivars with higher osmotically active solute content, higher tissue elastic adjustments and lower apoplastic water. Irreversible leaf damage was only observed in laboratory experiments at very low temperatures, but not in the field. A comparative analysis of closely related plants avoids phylogenetic independence bias in a comparative study of adaptations to survive low temperatures.
Hematopoietic stem cell transplantation‐associated thrombotic microangiopathy accompanied by renal arteriolar C4d deposition
Authors: Sakamoto Kenichi , Imamura Toshihiko , Osone Shinya , Nishimura Ayako , Nishida Masashi , Ishida Hiroyuki , Hosoi Hajime 
Published: March 2015

AbstractHSCT‐associated thrombotic microangiopathy (TA‐TMA) is a severe complication with a poor prognosis. Recently, it has been reported that complement system dysregulation, such as CFH autoantibodies and deletions CFH‐related genes 3 and 1, induced TA‐TMA. In addition, C4d‐positive renal arterioles are both a good marker of complement system activation and a useful diagnostic tool for TA‐TMA. Because dysregulation of the complement system is associated with TA‐TMA, the complement system might be a therapeutic target, such as eculizumab, a terminal complement inhibitor. Herein, we describe an eight‐yr‐old boy who developed TA‐TMA accompanied by severe renal dysfunction. His renal specimen showed diffuse C4d deposition in the renal arterioles, which is consistent with TA‐TMA. Although the patient gradually improved without eculizumab, renal arteriolar C4d staining in sample with TA‐TMA shows the complement system activation and may guide the target therapy using the eculizumab.
Biomodulation of Inflammatory Cytokines Related to Oral Mucositis by Low‐Level Laser Therapy
Authors: Basso Fernanda G. , Pansani Taisa N. , Soares Diana G. , Scheffel Débora L. , Bagnato Vanderlei S. , de Souza Costa Carlos Alberto , Hebling Josimeri 
Published: March 2015

AbstractThis study evaluated the effects of LLLT on the expression of inflammatory cytokines related to the development of oral mucositis by gingival fibroblasts. Primary gingival fibroblasts were seeded on 24‐well plates (105 cells/well) for 24 h. Fresh serum‐free culture medium (DMEM) was then added, and cells were placed in contact with LPS (Escherichia coli, 1 μg mL−1), followed by LLLT irradiation (LaserTABLE—InGaAsP diode prototype—780 nm, 25 mW) delivering 0, 0.5, 1.5 or 3 J cm−². Cells without contact with LPS were also irradiated with the same energy densities. Gene expression of TNF‐α, IL‐1β, IL‐6 and IL‐8 was evaluated by Real‐Time PCR, and protein synthesis of these cytokines was determined by enzyme‐linked immunosorbent (ELISA) assay. Data were statistically analyzed by the Kruskal–Wallis test, complemented by the Mann–Whitney test (P < 0.05). LPS treatment increased the gene expression and protein synthesis of TNF‐α, IL‐6 and IL‐8, while the expression of IL‐1β was not affected. For LPS‐treated groups, LLLT promoted significant decreases in the expression of TNF‐α, IL‐6, and IL‐8 at 1.5 J cm−2 and 3 J cm−2. These results demonstrate that LLLT promoted a beneficial biomodulatory effect on the expression of inflammatory cytokines related to oral mucositis by human gingival fibroblasts.
Assessment of microcirculatory perfusion in healthy anesthetized cats undergoing ovariohysterectomy using sidestream dark field microscopy
Authors: Goodnight Michelle E. , Cooper Edward S. , Butler Amy L. 
Published: March 2015

AbstractObjectiveTo: (1) determine the feasibility of using sidestream dark field microscopy (SDM) to measure microcirculatory parameters in healthy, anesthetized cats and (2) determine if surgical tissue manipulation and anesthesia time alter these parameters during ovariohysterectomy.DesignProspective observational study.SettingUniversity teaching hospital.AnimalsEighteen healthy female cats.InterventionsSublingual mucosa microcirculatory videos were obtained under general anesthesia preoperatively, intraoperatively, and postoperatively using an SDM device in healthy cats presenting for ovariohysterectomy. At each video acquisition point, macrovascular parameters (heart rate, blood pressure, pulse oximetry, end‐tidal CO2) were recorded. Vascular analysis software was used to calculate standard microcirculatory parameters. Multivariate analysis was performed to compare microvascular and macrovascular parameters, as well as correlation with the effect of surgical manipulation and time under anesthesia.Measurements and Main ResultsTwelve of 18 cats were included in final video analysis; 6 were removed for poor video quality. Values for total vessel density (TVD, 47.7 ± 8.39 mm/mm2), proportion of perfused vessels (PPV, 88.2 ± 5.95%), perfused vessel density (PVD, 43.0 ± 9.00 mm/mm2), microcirculatory flow index (MFI, 2.33 ± 0.33) were determined preoperatively. There were no significant changes in TVD, PPV, and PVD across intervention points. The MFI increased significantly from preoperative to intra‐ and postoperative data collection points. No correlation between microcirculatory parameters and length of anesthesia or macrocirculatory values was found.Conclusions and Clinical RelevanceThis study demonstrated that SDM can be utilized to obtain sublingual microvascular parameters in healthy, anesthetized cats. Limitations include difficulty in obtaining high quality images, presumed need for general anesthesia, and need for off‐line video analysis. This technology has potential as a tool in experimental and clinical monitoring of microcirculatory changes in felines.
Gene conversion events between GYPB and GYPE abolish expression of the S and s blood group antigens
Authors: Willemetz A. , Nataf J. , Thonier V. , Peyrard T. , Arnaud L. 
Published: March 2015

Background and ObjectiveThe locus specifying the MNS blood group system is composed of three highly homologous genes, glycophorin A (GYPA), B (GYPB) and E (GYPE). While more than 20 hybrid genes between GYPA and GYPB have been identified, no hybrid genes between GYPB and GYPE have been reported so far. We serendipitously identified GYPB‐E‐B hybrid genes by studying three individuals whose rare S−s− blood phenotype failed to be predicted by our genotyping platform.Materials and MethodsLong‐range PCR amplification and extended Sanger sequencing were required to identify and characterize these GYPB‐E‐B hybrid genes. A PCR assay was developed to detect them in individual or pooled gDNA samples.ResultsThe first S−s− proband appeared to have two silenced GYPB alleles, one harbouring the so‐called P2 mutation and one harbouring GYPE Pseudoexon E4 in place of GYPB Exon B4 (GYPB‐E‐B hybrid). The two other S−s− probands were homozygous or hemizygous for other GYPB‐E‐B hybrid alleles, which also lack GYPB Exon B4 and thus do not carry the S/s polymorphism.ConclusionThe three GYPB‐E‐B hybrid genes reported here constitute the first evidence of recombination events between GYPB and GYPE. As these GYPB‐E‐B hybrid genes drive the S−s− blood phenotype, it is important to know they are a limitation for the current blood group genotyping methods, including those performed by commercial platforms.
Analysis of the Upper Respiratory Tract Microbiotas as the Source of the Lung and Gastric Microbiotas in Healthy Individuals
Authors: Bassis Christine M. , Erb-Downward John R. , Dickson Robert P. , Freeman Christine M. , Schmidt Thomas M. , Young Vincent B. , Beck James M. , Curtis Jeffrey L. , Huffnagle Gary B. 
Published: March 2015

ABSTRACT
No studies have examined the relationships between bacterial communities along sites of the upper aerodigestive tract of an individual subject. Our objective was to perform an intrasubject and intersite analysis to determine the contributions of two upper mucosal sites (mouth and nose) as source communities for the bacterial microbiome of lower sites (lungs and stomach). Oral wash, bronchoalveolar lavage (BAL) fluid, nasal swab, and gastric aspirate samples were collected from 28 healthy subjects. Extensive analysis of controls and serial intrasubject BAL fluid samples demonstrated that sampling of the lungs by bronchoscopy was not confounded by oral microbiome contamination. By quantitative PCR, the oral cavity and stomach contained the highest bacterial signal levels and the nasal cavity and lungs contained much lower levels. Pyrosequencing of 16S rRNA gene amplicon libraries generated from these samples showed that the oral and gastric compartments had the greatest species richness, which was significantly greater in both than the richness measured in the lungs and nasal cavity. The bacterial communities of the lungs were significantly different from those of the mouth, nose, and stomach, while the greatest similarity was between the oral and gastric communities. However, the bacterial communities of healthy lungs shared significant membership with the mouth, but not the nose, and marked subject-subject variation was noted. In summary, microbial immigration from the oral cavity appears to be the significant source of the lung microbiome during health, but unlike the stomach, the lungs exhibit evidence of selective elimination of Prevotella bacteria derived from the upper airways.

IMPORTANCE
We have demonstrated that the bacterial communities of the healthy lung overlapped those found in the mouth but were found at lower concentrations, with lower membership and a different community composition. The nasal microbiome, which was distinct from the oral microbiome, appeared to contribute little to the composition of the lung microbiome in healthy subjects. Our studies of the nasal, oral, lung, and stomach microbiomes within an individual illustrate the microbiological continuity of the aerodigestive tract in healthy adults and provide culture-independent microbiological support for the concept that microaspiration is common in healthy individuals.
Finding the Sweet Spot: How Human Fungal Pathogens Acquire and Turn the Sugar Inositol against Their Hosts
Authors: Xue Chaoyang 
Published: March 2015

ABSTRACT

Inositol is an essential nutrient with important structural and signaling functions in eukaryotes. Its role in microbial pathogenesis has been reported in fungi, protozoans, and eubacteria. In a recent article, Porollo et al. [
mBio
5(6):e01834-14, 2014, doi:10.1128/mBio.01834-14] demonstrated the importance of inositol metabolism in the development and viability of Pneumocystis species—obligate fungal pathogens that remain unculturable
in vitro
. To understand their obligate nature, the authors used innovative comparative genomic approaches and discovered that Pneumocystis spp. are inositol auxotrophs due to the lack of inositol biosynthetic enzymes and that inositol insufficiency is a contributing factor preventing fungal growth
in vitro
. This work is in accord with other studies suggesting that inositol plays a conserved role in microbial pathogenesis. Inositol uptake and metabolism therefore may represent novel antimicrobial drug targets. Using comparative genomics to analyze metabolic pathways offers a powerful tool to gain new insights into nutrient utilization in microbes, especially obligate pathogens.
Glycan Engagement Dictates Hydrocephalus Induction by Serotype 1 Reovirus
Authors: Stencel-Baerenwald Jennifer , Reiss Kerstin , Blaum Bärbel S. , Colvin Daniel , Li Xiao-Nan , Abel Ty , Boyd Kelli , Stehle Thilo , Dermody Terence S. 
Published: March 2015

ABSTRACTReceptors expressed on the host cell surface adhere viruses to target cells and serve as determinants of viral tropism. Several viruses bind cell surface glycans to facilitate entry, but the contribution of specific glycan moieties to viral disease is incompletely understood. Reovirus provides a tractable experimental model for studies of viral neuropathogenesis. In newborn mice, serotype 1 (T1) reovirus causes hydrocephalus, whereas serotype 3 (T3) reovirus causes encephalitis. T1 and T3 reoviruses engage distinct glycans, suggesting that glycan-binding capacity contributes to these differences in pathogenesis. Using structure-guided mutagenesis, we engineered a mutant T1 reovirus incapable of binding the T1 reovirus-specific glycan receptor, GM2. The mutant virus induced substantially less hydrocephalus than wild-type virus, an effect phenocopied by wild-type virus infection of GM2-deficient mice. In comparison to wild-type virus, yields of mutant virus were diminished in cultured ependymal cells, the cell type that lines the brain ventricles. These findings suggest that GM2 engagement targets reovirus to ependymal cells in mice and illuminate the function of glycan engagement in reovirus serotype-dependent disease.IMPORTANCEReceptor utilization strongly influences viral disease, often dictating host range and target cell selection. Different reovirus serotypes bind to different glycans, but a precise function for these molecules in pathogenesis is unknown. We used type 1 (T1) reovirus deficient in binding the GM2 glycan and mice lacking GM2 to pinpoint a role for glycan engagement in hydrocephalus caused by T1 reovirus. This work indicates that engagement of a specific glycan can lead to infection of specific cells in the host and consequent disease at that site. Since reovirus is being developed as a vaccine vector and oncolytic agent, understanding reovirus-glycan interactions may allow manipulation of reovirus glycan-binding properties for therapeutic applications.