bluuebunny/crossref_metadata_2025 huggingface dataset:
Arsenic mobility and toxicity in South and South-east Asia – a review on biogeochemistry, health and socio-economic effects, remediation and risk predictions
Authors: Muehe E. Marie , Kappler Andreas
Published: September 2014

Environmental context The presence of high arsenic concentrations in South and South-east Asian groundwater causes dramatic health issues for the local population. As a consequence, scientists, governments and agencies investigate arsenic-related health issues and arsenic origin, fate and behaviour in ground- and drinking water and have started to provide remediation and mitigation strategies. This review broadly summarises our current knowledge on arsenic biogeochemistry, health and socio-economic effects, remediation and risk predications in Asia and discusses current and future research directions. Abstract The dramatic situation caused by high arsenic concentrations in ground and drinking water in South and South-east Asia has been investigated and discussed by the scientific community in the past twenty years. Multifaceted and interdisciplinary research extended our understanding of the origin, distribution and effects of As in this region of the world. Scientists have joined forces with local authorities and international non-governmental organisations (NGOs) and aid agencies to provide help, education, and assistance to the millions of people exposed to As. Current research focuses on predicting the behaviour of As in the subsurface, developing strategies to remove As from drinking water and remediating As-contaminated groundwater. This introductory review of the research front ‘Arsenic Biogeochemistry and Health’ gives a broad overview on the current knowledge of As biogeochemistry, exposure, health, toxicity and As-caused socioeconomic effects. Furthermore, the current research directions in predicting the presence and spreading of As in groundwater, assessing its risk and potential strategies to remove As from drinking water and to remediate contaminated environments are discussed.
Twitter tweets and twaddle: twittering at AHPA's National Health Promotion Conference
Authors: Anderson George , Gleeson Suzanne , Rissel Chris , Wen Li Ming , Bedford Karen
Published: September 2014

Issue addressed

This paper explored the first‐time use of Twitter by the Australian Health Promotion Association (AHPA) at its 2013 National Health Promotion Conference.

Methods

The @AHPA_AU Twitter account and #AHPA2013 hashtag were established and included in the conference program. Attendees were encouraged throughout the conference to use it. A total of 748 tweets were captured under the hashtag #AHPA2013 in chronological order from 16–19 June 2013. Tweets with photos and more than one hashtag were recorded. A thematic analysis of tweets was conducted.

Results

Thirteen broad themes were identified, with each of the 748 tweets allocated to one of the themes. Tweets about keynote sessions made up 38% of all tweets, followed by 14% for concurrent sessions. A photo was included in 11% of tweets, and 25% were sent to more than one hashtag. There were 96 tweeters; 75% of them posted five or less tweets and ~9%, including a professional blogger, posted greater than 20 tweets. At the Aboriginal and Torres Strait Islander pre‐conference workshop there was a relatively high level of Twitter engagement.

Conclusion

Twitter could potentially be useful for promoting conference content and activities, but what it adds in value to a health promotion conference cannot be determined by this study.

So what?

This paper highlights the engagement of tweeters with conference content and activities and suggests that tweeting benefited from the engagement of a professional health blogger.
Review of policies and guidelines concerning adults’ alcohol consumption and promotion in Australian government schools
Authors: Ward Bernadette M. , Buykx Penelope , Munro Geoff , Hausdorf Katrin , Wiggers John
Published: September 2014

Issue addressed

Schools are recognised as important settings for promoting student and community wellbeing through education, policies and the modelling of behaviour. Recently, there has been controversy regarding the promotion and use of alcohol by adults at school events. The aim of this study was to examine the policy approach of all Australian jurisdictions to the possession and use of alcohol, by adults, at government school events when students are present.

Methods

A desktop review of Australian governments' alcohol in schools policy/guidelines documents was undertaken.

Results

Eighteen documents across eight jurisdictions were retrieved. There were inconsistencies between jurisdictions and lack of policy clarity regarding the promotion and/or use of alcohol by adults at events organised by schools for recreation, celebration and fundraising purposes.

Discussion and conclusions

Clarity is needed about the role of alcohol in Australian schools, particularly in relation to its use of alcohol when there is a duty of care to children. The possession and/or use of alcohol by adults at school events may contribute to the pervasive role of drinking in Australian social life.

So what?

Clear and evidence‐based guidelines are needed to inform school policies across all jurisdictions as to whether, when and under which circumstances it is appropriate for schools to promote and/or supply alcohol. This would also strengthen the ability of school principals and communities to make appropriate evidence‐based decisions that focus on the interests of children.
Exploring matrix effects on photochemistry of organic aerosols
Authors: Lignell Hanna , Hinks Mallory L. , Nizkorodov Sergey A.
Published: September 2014

Significance

Recent discovery of highly viscous materials in organic aerosols prompted atmospheric scientists to reevaluate their views of organic particle growth and chemical aging. This work reveals dramatic differences in the effect of temperature on photolysis efficiency of organic compounds trapped in viscous organic matrix, in a liquid organic solvent, and in an aqueous solution. Given the paramount role of photochemistry in driving the chemical reactions in the environment, these results will have significant implications for predicting lifetimes of photolabile atmospheric organic compounds, including environmental toxins, trapped in organic particles. This work also demonstrates that changing from water to an organic solvent can drastically enhance photochemical activity of environmental toxins, thus underscoring the importance of particle-phase photochemistry.
Neural mechanism of optimal limb coordination in crustacean swimming
Authors: Zhang Calvin , Guy Robert D. , Mulloney Brian , Zhang Qinghai , Lewis Timothy J.
Published: September 2014

Significance

Despite the general belief that neural circuits have evolved to optimize behavior, few studies have clearly identified the neural mechanisms underlying optimal behavior. The distinct limb coordination in crustacean swimming and the relative simplicity of the neural coordinating circuit have allowed us to show that the interlimb coordination in crustacean swimming is biomechanically optimal and how the structure of underlying neural circuit robustly gives rise to this coordination. Thus, we provide a concrete example of how an optimal behavior arises from the anatomical structure of a neural circuit. Furthermore, our results suggest that the connectivity of the neural circuit underlying limb coordination during crustacean swimming may be a consequence of natural selection in favor of more effective and efficient swimming.
Homeostatic IL-23 receptor signaling limits Th17 response through IL-22–mediated containment of commensal microbiota
Authors: Shih Vincent Feng-Sheng , Cox Jennifer , Kljavin Noelyn M. , Dengler Hart S. , Reichelt Mike , Kumar Pawan , Rangell Linda , Kolls Jay K. , Diehl Lauri , Ouyang Wenjun , Ghilardi Nico
Published: September 2014

Significance

Commensal microbiota are known to be required for the elicitation of host Th17 responses, which may mediate autoimmune diseases. Here, we demonstrate that the IL-23 pathway dynamically regulates the abundance of certain commensals and maintains barrier function. Barrier disruption results in systemic dissemination of microbial products, which invokes the IL-23 pathway, with both beneficial and potentially deleterious consequences. Through induction of IL-22, IL-23 contributes to barrier repair, and through induction of the Th17 response, it aims to neutralize escaped commensal microbes. Thus, barrier disruption results in a pro-Th17 environment in which not only antimicrobial but also potentially antihost Th17 cells can develop.
Global genomic and transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism
Authors: Fadista João , Vikman Petter , Laakso Emilia Ottosson , Mollet Inês Guerra , Esguerra Jonathan Lou , Taneera Jalal , Storm Petter , Osmark Peter , Ladenvall Claes , Prasad Rashmi B. , Hansson Karin B. , Finotello Francesca , Uvebrant Kristina , Ofori Jones K. , Di Camillo Barbara , Krus Ulrika , Cilio Corrado M. , Hansson Ola , Eliasson Lena , Rosengren Anders H. , Renström Erik , Wollheim Claes B. , Groop Leif
Published: September 2014

Significance

We provide a comprehensive catalog of novel genetic variants influencing gene expression and metabolic phenotypes in human pancreatic islets. The data also show that the path from genetic variation (SNP) to gene expression is more complex than hitherto often assumed, and that we need to consider that genetic variation can also influence function of a gene by influencing exon usage or splice isoforms (sQTL), allelic imbalance, RNA editing, and expression of noncoding RNAs, which in turn can influence expression of target genes.
Pleckstrin homology domain leucine-rich repeat protein phosphatases set the amplitude of receptor tyrosine kinase output
Authors: Reyes Gloria , Niederst Matt , Cohen-Katsenelson Ksenya , Stender Joshua D. , Kunkel Maya T. , Chen Muhan , Brognard John , Sierecki Emma , Gao Tianyan , Nowak Dawid G. , Trotman Lloyd C. , Glass Christopher K. , Newton Alexandra C.
Published: September 2014

Significance

This work unveils a previously unidentified function of the tumor suppressor pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) in inhibiting oncogenic signaling by suppressing the steady-state levels of receptor tyrosine kinases such as the EGF receptor. Specifically, PHLPP modifies the histone code to control the transcription of receptor tyrosine kinases. This epigenetic function can account for the upregulation of receptor tyrosine kinases in the multiple cancer types where PHLPP function is compromised.
Myosins XI modulate host cellular responses and penetration resistance to fungal pathogens
Authors: Yang Long , Qin Li , Liu Guosheng , Peremyslov Valera V. , Dolja Valerian V. , Wei Yangdou
Published: September 2014

Significance

Remodeling of actin cytoskeleton is thought to contribute to the establishment of effective barriers at the periphery of plant cells against fungal ingress. However, there is little information on the molecular mechanisms that regulate actin remodeling during interactions with invading pathogens. Here we show that disruption of myosin motors in
Arabidopsis
prevents dynamic reorganizations of actin filaments, focal organelle accumulation, and delivery of cell wall defense compounds toward the pathogen penetration site. Furthermore, the quadruple knockout mutant of class XI myosins exhibits impaired penetration resistance at the cell wall and enhanced overall disease susceptibility to both adapted and nonadapted fungal pathogens. This study provides insights into how myosins regulate cellular responses that contribute to plant immunity.
Visual stimuli recruit intrinsically generated cortical ensembles
Authors: Miller Jae-eun Kang , Ayzenshtat Inbal , Carrillo-Reid Luis , Yuste Rafael
Published: September 2014

Significance

This study demonstrates that neuronal groups or ensembles, rather than individual neurons, are emergent functional units of cortical activity. We show that in the presence and absence of visual stimulation, cortical activity is dominated by coactive groups of neurons forming ensembles. These ensembles are flexible and cannot be accounted for by the independent firing properties of neurons in isolation. Intrinsically generated ensembles and stimulus-evoked ensembles are similar, with one main difference: Whereas intrinsic ensembles recur at random time intervals, visually evoked ensembles are time-locked to stimuli. We propose that visual stimuli recruit endogenously generated ensembles to represent visual attributes.
Motor coupling through lipid membranes enhances transport velocities for ensembles of myosin Va
Authors: Nelson Shane R. , Trybus Kathleen M. , Warshaw David M.
Published: September 2014

Significance

Intracellular cargo transport is carried out by ensembles of cytoskeleton-based molecular motors, such as myosin Va. Physiologically, motor molecules are bound to (and mechanically coupled through) the vesicular membrane, which is a fluid lipid bilayer. Utilizing a combination of experiment and computer simulation, we characterize the influence of three distinct aspects of the vesicular ensemble (vesicle size, membrane composition, and motor density) on cargo transport. We also demonstrate the presence of vesicle populations that travel at velocities up to twice the unloaded velocity of a single motor. These findings serve to bridge the gap between enhanced vesicular velocities measured in vivo and depressed velocities measured in vitro.
Experimental realization of a Szilard engine with a single electron
Authors: Koski Jonne V. , Maisi Ville F. , Pekola Jukka P. , Averin Dmitri V.
Published: September 2014

Significance

A Maxwell demon makes use of information to convert thermal energy of a reservoir into work. A quantitative example is a thought experiment known as a Szilard engine, which uses one bit of information about the position of a thermalized molecule in a box to extract
k

B

T
ln 2 of work. The second law of thermodynamics remains valid because, according to Landauer principle, erasure of the information dissipates at least the same amount of heat. Here, we present an experimental realization of a Maxwell demon similar to a Szilard engine, in the form of a single electron box. We provide, to our knowledge, the first demonstration of extracting nearly
k

B

T
ln 2 of work for one bit of information.
Channelrhodopsin-2–XXL, a powerful optogenetic tool for low-light applications
Authors: Dawydow Alexej , Gueta Ronnie , Ljaschenko Dmitrij , Ullrich Sybille , Hermann Moritz , Ehmann Nadine , Gao Shiqiang , Fiala André , Langenhan Tobias , Nagel Georg , Kittel Robert J.
Published: September 2014

Significance

Controlling neuronal activity in live tissue is a long sought-after goal in the neurosciences. Channelrhodopsin-2 (ChR2) is a microbial-type rhodopsin that can be genetically expressed to depolarize neurons with light. Thereby, this “optogenetic tool” delivers cellular specificity and elegant options for studying the neuronal basis of behavior in intact organisms. Unfortunately, low-light transmission through pigmented tissue greatly complicates light delivery to target cells and curtails experiments in freely moving animals. This study introduces a ChR mutant, ChR2-XXL, that gives rise to the largest photocurrents of all ChRs published so far and increases light sensitivity more than 10,000-fold over wild-type ChR2 in
Drosophila
larvae. As a result, behavioral photostimulation is evoked in freely moving flies using diffuse, ambient light.
Maturation of cortical circuits requires Semaphorin 7A
Authors: Carcea Ioana , Patil Shekhar B. , Robison Alfred J. , Mesias Roxana , Huntsman Molly M. , Froemke Robert C. , Buxbaum Joseph D. , Huntley George W. , Benson Deanna L.
Published: September 2014

Significance

Sensory experience exerts profound control over the structure and function of developing cortical circuits during an early postnatal critical period. Abnormalities in this process contribute to perceptual and cognitive deficits, but molecular mechanisms generating excitatory and inhibitory cortical networks during this period remain poorly understood. We show here that Semaphorin 7A (Sema7A) is highly expressed in mouse somatosensory cortex when tactile information conveyed by the thalamus shapes development of somatosensory cortical networks. In mice lacking Sema7A, the anatomical layout of the somatosensory cortex is disrupted, dendritic arbors are misoriented, inhibitory connections develop abnormally, and thalamocortical activity fails to elicit a normal balance of excitation and inhibition. Taken together, our data indicate that maturation of thalamocortical and local circuits in cortex requires Sema7A.
Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas
Authors: Duque-Correa María A. , Kühl Anja A. , Rodriguez Paulo C. , Zedler Ulrike , Schommer-Leitner Sandra , Rao Martin , Weiner January , Hurwitz Robert , Qualls Joseph E. , Kosmiadi George A. , Murray Peter J. , Kaufmann Stefan H. E. , Reece Stephen T.
Published: September 2014

Significance

Tuberculosis (TB) granulomas represent sites of both bacterial containment and tissue pathology. Macrophage killing of
Mycobacterium tuberculosis
(
Mtb
) in granulomas to contain infection must be regulated to prevent collateral tissue damage. Nitric oxide synthase-2 (NOS2) and arginase-1 (Arg1), macrophage enzymes metabolizing
l
-arginine, play key roles in this process. NOS2 produces reactive nitrogen intermediates to kill
Mtb
, whereas Arg1 regulates NOS2 activity via substrate competition. Arg1 activity could predominate in hypoxic regions of granulomas where NOS2 activity likely is suboptimal. Here we show that Arg1 plays a central role in restricting bacterial growth and restraining tissue damage within granulomas in TB and other chronic inflammatory diseases. These findings point to the modulation of Arg1 activity as a potential host-directed therapy for TB.
Biophysical implications of lipid bilayer rheometry for mechanosensitive channels
Authors: Bavi Navid , Nakayama Yoshitaka , Bavi Omid , Cox Charles D. , Qin Qing-Hua , Martinac Boris
Published: September 2014

Significance

Given the extensive use of lipid bilayer reconstitution for the study of mechanosensitive channels, it is imperative to understand the biophysical properties of lipid bilayers. We have theoretically and experimentally proven that the traditional micropipette aspiration method fails to accurately describe these properties. Herein we introduce a superior framework, which combines computational modeling with patch fluorometry for the assessment of bilayer properties. Our results show the limitations of Laplace’s law for estimation of tension within a patch membrane. We also demonstrate, in contrast to the cell-attached configuration, there is a significant difference between the stress developed in the outer and in the inner monolayers of the bilayer in the excised patch configuration. These results are of critical importance for patch-clamp electrophysiology in general.
Evolution of ibrutinib resistance in chronic lymphocytic leukemia (CLL)
Authors: Komarova Natalia L. , Burger Jan A. , Wodarz Dominik
Published: September 2014

Significance

Chronic ymphocytic leukemia is the most common leukemia, mostly arising in patients over the age of 50. The disease has been treated with chemo-immunotherapies with varying outcomes, depending on the genetic make-up of the tumor cells. Recently, a promising new tyrosine kinase inhibitor, ibrutinib, has been developed, which resulted in successful responses in clinical trials, even for the most aggressive chronic lymphocytic leukemia types. The crucial current questions include how long disease control can be maintained in individual patients, when drug resistance is expected to arise, and what can be done to counter it. Computational evolutionary models, based on measured kinetic parameters of patients, allow us to address these questions and to pave the way toward a personalized prognosis.
Mantle updrafts and mechanisms of oceanic volcanism
Authors: Anderson Don L. , Natland James H.
Published: September 2014

Significance

Lord Kelvin’s name is associated with the laws of thermodynamics and the cooling Earth hypothesis. The widely accepted mantle plume conjecture has been justified by experiments and calculations that violate the laws of thermodynamics for an isolated cooling planet. Hotspots such as Hawaii, Samoa, Iceland, and Yellowstone are due to a thermal bump in the shallow mantle, a consequence of the cooling of the Earth. They are not due to ∼100- to 200-km-wide tubes extending upward from fixed points near the Earth’s core. Seismic imaging shows that features associated with hotspots are thousands of kilometers across, and inferred ascent rates are low. Plate tectonic-induced updrafts and a cooling planet explain hotspots and the volcanoes at oceanic ridges.
On the absence of sternal elements inAnchiornis(Paraves) andSapeornis(Aves) and the complex early evolution of the avian sternum
Authors: Zheng Xiaoting , O’Connor Jingmai , Wang Xiaoli , Wang Min , Zhang Xiaomei , Zhou Zhonghe
Published: September 2014

Significance

We have observed more than 200 specimens ofAnchiornis, the earliest known feathered dinosaur, and nearly 100 specimens ofSapeornis, one of the basalmost birds, and recognize no sternal ossifications. We propose that the sternum may have been completely lost in these two taxa (andArchaeopteryxas well) based on histological analysis and the excellent preservation of soft-tissue structures, thus suggesting the absence of a sternum could represent the plesiomorphic avian condition. Our discovery reveals an unexpected level of complexity and high degree of inherent developmental plasticity in the early evolution of the avian sternum.
Synthetic routes contaminate graphene materials with a whole spectrum of unanticipated metallic elements
Authors: Wong Colin Hong An , Sofer Zdeněk , Kubešová Marie , Kučera Jan , Matějková Stanislava , Pumera Martin
Published: September 2014

Significance

Graphene is well-poised to revolutionize many industries because of its multitude of exceptional properties. Current bulk synthesis of graphene materials typically starts with the oxidation of graphite to graphite oxide followed by a reduction step. Many different methods exist for both the oxidation and reduction steps, leading to highly variable types and amounts of metallic contaminations that originate from the reagents themselves. These impurities are able to alter the graphene materials’ properties significantly, which impacts the range of potential applications for which these graphene materials are suitable. Thus, proper characterization of metallic contamination is highly important to ensure the suitability of a chosen set of synthetic procedures to the final application of the graphene material.
Neuronal necrosis is regulated by a conserved chromatin-modifying cascade
Authors: Liu Kai , Ding Lianggong , Li Yuhong , Yang Hui , Zhao Chunyue , Lei Ye , Han Shuting , Tao Wei , Miao Dengshun , Steller Hermann , Welsh Michael J. , Liu Lei
Published: September 2014

Significance

Neuronal necrosis widely occurs in devastating neurodegenerative diseases, such as stroke, traumatic brain injury, and Alzheimer’s disease. However, it has long been considered a stochastic process lacking genetic regulations. Our inadequate understanding of its molecular mechanism has hindered pharmacological design to suppress this type of cell death. Through construction and studying of a
Drosophila
model of neuronal necrosis, we identified a chromatin-modifying cascade to play a key role in execution of neuronal necrosis. Our results indicate that neuronal necrosis is a stereotypically regulated process in both insect and mammalian neurons. This discovery provides previously unidentified biomarkers and potential therapeutic targets for neuronal necrosis.
Calcium sensitive ring-like oligomers formed by synaptotagmin
Authors: Wang Jing , Bello Oscar , Auclair Sarah M. , Wang Jing , Coleman Jeff , Pincet Frederic , Krishnakumar Shyam S. , Sindelar Charles V. , Rothman James E.
Published: September 2014

Significance

Synaptotagmin-1 is the calcium sensor for synchronous neurotransmitter release. It couples calcium influx to the soluble
N
-ethylmaleimide–sensitive factor activating protein receptor (SNARE)-catalyzed fusion, but how this coupling happens is unknown. Here, using electron microscopy, we report that the cytosolic domain of synaptotagmin can assemble into ring-like oligomers under calcium-free conditions, and these rings disassemble rapidly upon calcium binding. This process suggests a novel but speculative mechanism to explain calcium coupling, in which the synaptotagmin rings separate the vesicle and plasma membranes and prevent the completion of SNARE complex assembly until the influx of calcium.
Concentration of Sec12 at ER exit sites via interaction with cTAGE5 is required for collagen export
Authors: Saito Kota , Yamashiro Koh , Shimazu Noriko , Tanabe Tomoya , Kontani Kenji , Katada Toshiaki
Published: September 2014

Mechanisms for exporting variably sized cargo from the endoplasmic reticulum (ER) using the same machinery remain poorly understood. COPII-coated vesicles, which transport secretory proteins from the ER to the Golgi apparatus, are typically 60–90 nm in diameter. However, collagen, which forms a trimeric structure that is too large to be accommodated by conventional transport vesicles, is also known to be secreted via a COPII-dependent process. In this paper, we show that Sec12, a guanine-nucleotide exchange factor for Sar1 guanosine triphosphatase, is concentrated at ER exit sites and that this concentration of Sec12 is specifically required for the secretion of collagen VII but not other proteins. Furthermore, Sec12 recruitment to ER exit sites is organized by its direct interaction with cTAGE5, a previously characterized collagen cargo receptor component, which functions together with TANGO1 at ER exit sites. These findings suggest that the export of large cargo requires high levels of guanosine triphosphate–bound Sar1 generated by Sec12 localized at ER exit sites.
Expression of HSF2 decreases in mitosis to enable stress-inducible transcription and cell survival
Authors: Elsing Alexandra N. , Aspelin Camilla , Björk Johanna K. , Bergman Heidi A. , Himanen Samu V. , Kallio Marko J. , Roos-Mattjus Pia , Sistonen Lea
Published: September 2014

Unless mitigated, external and physiological stresses are detrimental for cells, especially in mitosis, resulting in chromosomal missegregation, aneuploidy, or apoptosis. Heat shock proteins (Hsps) maintain protein homeostasis and promote cell survival. Hsps are transcriptionally regulated by heat shock factors (HSFs). Of these, HSF1 is the master regulator and HSF2 modulates Hsp expression by interacting with HSF1. Due to global inhibition of transcription in mitosis, including HSF1-mediated expression of Hsps, mitotic cells are highly vulnerable to stress. Here, we show that cells can counteract transcriptional silencing and protect themselves against proteotoxicity in mitosis. We found that the condensed chromatin of HSF2-deficient cells is accessible for HSF1 and RNA polymerase II, allowing stress-inducible Hsp expression. Consequently, HSF2-deficient cells exposed to acute stress display diminished mitotic errors and have a survival advantage. We also show that HSF2 expression declines during mitosis in several but not all human cell lines, which corresponds to the Hsp70 induction and protection against stress-induced mitotic abnormalities and apoptosis.
Activation of RhoA-ROCK-BMP signaling reprograms adult human corneal endothelial cells
Authors: Zhu Ying-Ting , Li Fu , Han Bo , Tighe Sean , Zhang Suzhen , Chen Szu-Yu , Liu Xin , Tseng Scheffer C.G.
Published: September 2014

Currently there are limited treatment options for corneal blindness caused by dysfunctional corneal endothelial cells. The primary treatment involves transplantation of healthy donor human corneal endothelial cells, but a global shortage of donor corneas necessitates other options. Conventional tissue approaches for corneal endothelial cells are based on EDTA-trypsin treatment and run the risk of irreversible endothelial mesenchymal transition by activating canonical Wingless-related integration site (Wnt) and TGF-β signaling. Herein, we demonstrate an alternative strategy that avoids disruption of cell–cell junctions and instead activates Ras homologue gene family A (RhoA)–Rho-associated protein kinase (ROCK)–canonical bone morphogenic protein signaling to reprogram adult human corneal endothelial cells to neural crest–like progenitors via activation of the miR302b-Oct4-Sox2-Nanog network. This approach allowed us to engineer eight human corneal endothelial monolayers of transplantable size, with a normal density and phenotype from one corneoscleral rim. Given that a similar signal network also exists in the retinal pigment epithelium, this partial reprogramming approach may have widespread relevance and potential for treating degenerative diseases.
Dlg1 controls planar spindle orientation in the neuroepithelium through direct interaction with LGN
Authors: Saadaoui Mehdi , Machicoane Mickaël , di Pietro Florencia , Etoc Fred , Echard Arnaud , Morin Xavier
Published: September 2014

Oriented cell divisions are necessary for the development of epithelial structures. Mitotic spindle orientation requires the precise localization of force generators at the cell cortex via the evolutionarily conserved LGN complex. However, polarity cues acting upstream of this complex in vivo in the vertebrate epithelia remain unknown. In this paper, we show that Dlg1 is localized at the basolateral cell cortex during mitosis and is necessary for planar spindle orientation in the chick neuroepithelium. Live imaging revealed that Dlg1 is required for directed spindle movements during metaphase. Mechanistically, we show that direct interaction between Dlg1 and LGN promotes cortical localization of the LGN complex. Furthermore, in human cells dividing on adhesive micropatterns, homogenously localized Dlg1 recruited LGN to the mitotic cortex and was also necessary for proper spindle orientation. We propose that Dlg1 acts primarily to recruit LGN to the cortex and that Dlg1 localization may additionally provide instructive cues for spindle orientation.
Oral-resident natural Th17 cells and γδ T cells control opportunistic Candida albicans infections
Authors: Conti Heather R. , Peterson Alanna C. , Brane Lucas , Huppler Anna R. , Hernández-Santos Nydiaris , Whibley Natasha , Garg Abhishek V. , Simpson-Abelson Michelle R. , Gibson Gregory A. , Mamo Anna J. , Osborne Lisa C. , Bishu Shrinivas , Ghilardi Nico , Siebenlist Ulrich , Watkins Simon C. , Artis David , McGeachy Mandy J. , Gaffen Sarah L.
Published: September 2014

Oropharyngeal candidiasis (OPC) is an opportunistic fungal infection caused by Candida albicans. OPC is frequent in HIV/AIDS, implicating adaptive immunity. Mice are naive to Candida, yet IL-17 is induced within 24 h of infection, and susceptibility is strongly dependent on IL-17R signaling. We sought to identify the source of IL-17 during the early innate response to candidiasis. We show that innate responses to Candida require an intact TCR, as SCID, IL-7Rα−/−, and Rag1−/− mice were susceptible to OPC, and blockade of TCR signaling by cyclosporine induced susceptibility. Using fate-tracking IL-17 reporter mice, we found that IL-17 is produced within 1–2 d by tongue-resident populations of γδ T cells and CD3+CD4+CD44hiTCRβ+CCR6+ natural Th17 (nTh17) cells, but not by TCR-deficient innate lymphoid cells (ILCs) or NK cells. These cells function redundantly, as TCR-β−/− and TCR-δ−/− mice were both resistant to OPC. Whereas γδ T cells were previously shown to produce IL-17 during dermal candidiasis and are known to mediate host defense at mucosal surfaces, nTh17 cells are poorly understood. The oral nTh17 population expanded rapidly after OPC, exhibited high TCR-β clonal diversity, and was absent in Rag1−/−, IL-7Rα−/−, and germ-free mice. These findings indicate that nTh17 and γδ T cells, but not ILCs, are key mucosal sentinels that control oral pathogens.
Regulation of proximal T cell receptor signaling and tolerance induction by deubiquitinase Usp9X
Authors: Naik Edwina , Webster Joshua D. , DeVoss Jason , Liu Jinfeng , Suriben Rowena , Dixit Vishva M.
Published: September 2014

The T cell hyperproliferation and autoimmune phenotypes that manifest in mice lacking E3 ubiquitin ligases such as Cbl, ITCH, or GRAIL highlight the importance of ubiquitination for the maintenance of peripheral T cell tolerance. Less is known, however, about the deubiquitinating enzymes that regulate T cell proliferation and effector function. Here, we define a cell intrinsic role for the deubiquitinase Usp9X during proximal TCR signaling. Usp9X-deficient T cells were hypoproliferative, yet mice with T cell–specific Usp9x deletion had elevated numbers of antigen-experienced T cells and expanded PD-1 and OX40-expressing populations consistent with immune hyperactivity. Aged Usp9x KO mice developed lupus-like autoimmunity and lymphoproliferative disease, indicating that ubiquitin ligases and deubiquitinases maintain the delicate balance between effective immunity and self-tolerance.
Quantum supergroups II. Canonical basis
Authors: Clark Sean , Hill David , Wang Weiqiang
Published: September 2014

Following Kashiwara’s algebraic approach, we construct crystal bases and canonical bases for quantum supergroups of anisotropic type and for their integrable modules.
Increased Diaphragmatic Contribution to Inspiratory Effort during Neurally Adjusted Ventilatory Assistance versus Pressure Support
Authors: Cecchini Jérôme , Schmidt Matthieu , Demoule Alexandre , Similowski Thomas
Published: September 2014

Background:

Neurally adjusted ventilatory assist (NAVA), regulated exclusively by the electromyographic activity (EA) of the diaphragm (EAdi), could affect the distribution of neural drive to the various inspiratory muscles. The objective of this study was to compare EAdi, EA of the scalene (EAscal), and EA of the alae nasi (EAan), according to the ventilatory mode and assist level in 12 mechanically ventilated patients.

Methods:

Seven assist levels of pressure support ventilation (PSV) and NAVA were sequentially applied. EAdi, EAscal, and EAan were quantified and expressed as a percentage of their maximum values. The relative contributions of extradiaphragmatic muscles to inspiratory efforts were assessed by calculating EAscal/EAdi and EAan/EAdi ratios. Three assist levels for each of the two ventilatory modes that resulted in EAdi values of 80 to 100%, 60 to 80%, and 40 to 60% were assigned to three groups (N1, N2, and N3). Results are expressed as median and interquartile range.

Results:

EA of inspiratory muscles decreased during PSV and NAVA (P < 0.0001). Although EAdi remained constant within groups (P = 0.9), EAscal was reduced during NAVA compared with PSV in N1 and N3 (65% [62 to 64] and 27% [18 to 34] in NAVA vs. 90% [81 to 100] and 49% [40 to 55] in PSV, P = 0.007). Altogether, EAscal/EAdi and EAan/EAdi ratios were lower in NAVA than PSV (0.7 [0.6 to 0.7] and 0.7 [0.6 to 0.8] in NAVA vs. 0.9 [0.8 to 1.1] and 0.9 [0.7 to 1.1] in PSV, P < 0.05).

Conclusions:

NAVA and PSV both reduced extradiaphragmatic inspiratory muscle activity, in proportion to the level of assistance. Compared with PSV, NAVA resulted in a predominant contribution of the diaphragm to inspiratory effort.
Brain Serotonin Content Regulates the Manifestation of Tramadol-induced Seizures in Rats
Authors: Fujimoto Yohei , Funao Tomoharu , Suehiro Koichi , Takahashi Ryota , Mori Takashi , Nishikawa Kiyonobu
Published: September 2014

Background:

Tramadol-induced seizures might be pathologically associated with serotonin syndrome. Here, the authors investigated the relationship between serotonin and the seizure-inducing potential of tramadol.

Methods:

Two groups of rats received pretreatment to modulate brain levels of serotonin and one group was treated as a sham control (n = 6 per group). Serotonin modulation groups received either para-chlorophenylalanine or benserazide + 5-hydroxytryptophan. Serotonin, dopamine, and histamine levels in the posterior hypothalamus were then measured by microdialysis, while simultaneously infusing tramadol until seizure onset. In another experiment, seizure threshold with tramadol was investigated in rats intracerebroventricularly administered with either a serotonin receptor antagonist (methysergide) or saline (n = 6).

Results:

Pretreatment significantly affected seizure threshold and serotonin fluctuations. The threshold was lowered in para-chlorophenylalanine group and raised in benserazide + 5-hydroxytryptophan group (The mean ± SEM amount of tramadol needed to induce seizures; sham: 43.1 ± 4.2 mg/kg, para-chlorophenylalanine: 23.2 ± 2.8 mg/kg, benserazide + 5-hydroxytryptophan: 59.4 ± 16.5 mg/kg). Levels of serotonin at baseline, and their augmentation with tramadol infusion, were less in the para-chlorophenylalanine group and greater in the benserazide + 5-hydroxytryptophan group. Furthermore, seizure thresholds were negatively correlated with serotonin levels (correlation coefficient; 0.71, P < 0.01), while intracerebroventricular methysergide lowered the seizure threshold (P < 0.05 vs. saline).

Conclusions:

The authors determined that serotonin-reduced rats were predisposed to tramadol-induced seizures, and that serotonin concentrations were negatively associated with seizure thresholds. Moreover, serotonin receptor antagonism precipitated seizure manifestation, indicating that tramadol-induced seizures are distinct from serotonin syndrome.
Duodenal Hematoma Following EGD
Authors: Sahn Benjamin , Anupindi Sudha A. , Dadhania Neha J. , Kelsen Judith R. , Nance Michael L. , Mamula Petar
Published: September 2014

Background:

Duodenal hematoma (DH) is a rare complication of esophagogastroduodenoscopy (EGD) with duodenal biopsy and uncommon, but better described following blunt abdominal trauma (BAT). We aimed to describe DH incidence and investigate risk factors for DH development post‐EGD and compare its features to those post‐BAT.

Methods:

Multiple electronic databases were searched for the diagnosis of DH from 2000 to 2012. Inclusion criteria were patients 0 to 21 years of age who developed a DH following EGD with biopsy or BAT. Exclusion criteria were DH secondary to any other mechanism, EGD performed at another medical center, and insufficient information in the electronic medical record to determine treatments or outcomes.

Results:

A total of 14 post‐EGD and 15 post‐BAT patients with DH were included in the study. There were 26,905 EGDs with duodenal biopsies performed during the study period, for an incidence of 1:1922 procedures. Thirteen of 14 (93%) post‐EGD DH events occurred between 2007 and 2012 (P < 0.001). The proportion of procedures performed under general anesthesia versus moderate sedation, and performed in the supine position versus left lateral decubitus were close to but did not reach statistical significance. DH‐related complications and time to hematoma resolution was similar between groups.

Conclusions:

In a 13‐year study period, 14 patients developed DH after EGD, for an incidence of 1:1922. Method of sedation and supine positioning of the patient during endoscopy warrant further investigation as potential risks. The clinical course and time to recovery with conservative management are similar between patients with EGD and BAT‐induced DH.
Analysis of Adverse Events Associated With Adult Moderate Procedural Sedation Outside the Operating Room
Authors: Karamnov Sergey , Sarkisian Natalia , Grammer Rebecca , Gross Wendy L. , Urman Richard D.
Published: September 2014

Introduction

Moderate sedation outside the operating room is performed for a variety of medical and surgical procedures. It involves the administration of different drug combinations by nonanesthesia professionals. Few data exist on risk stratification and patient outcomes in the adult population. Current literature suggests that sedation can be associated with significant adverse outcomes.

Objectives

The aims of this study were to evaluate the nature of adverse events associated with moderate sedation and to examine their relation to patient characteristics and outcomes.

Methods

In this retrospective review, 52 cases with moderate sedation safety incidents were identified out of approximately 143,000 cases during an 8-year period at a tertiary care medical center. We describe types of adverse events and the severity of associated harm. We used bivariate and multivariate analyses to examine the links between event types and both patient and procedure characteristics.

Results

The most common adverse event and unplanned intervention were oversedation leading to apnea (57.7% of cases) and the use of reversal agents (55.8%), respectively. Oversedation, hypoxemia, reversal agent use, and prolonged bag-mask ventilation were most common in cardiology (84.6%, 53.9%, 84.6%, and 38.5% of cases, respectively) and gastroenterology (87.5%, 75%, 87.5%, and 50%) suites. Miscommunication was reported most frequently in the emergency department (83.3%) and on the inpatient floor (69.2%). Higher body mass index was associated with increased rates of hypoxemia and intubation but lower rates of hypotension. Advanced age boosted the rates of oversedation, hypoxemia, and reversal agent use. Women were more likely than men to experience oversedation, hypotension, prolonged bag-mask ventilation, and reversal agent use. Patient harm was associated with age, body mass index, comorbidities, female sex, and procedures in the gastroenterology suite.

Conclusions

Providers should take into account patient characteristics and procedure types when assessing the risks of harmful sedation-related complications.
A measurement of
G
with a cryogenic torsion pendulum
Authors: Newman Riley , Bantel Michael , Berg Eric , Cross William
Published: September 2014

A measurement of Newton's gravitational constant
G
has been made with a cryogenic torsion pendulum operating below 4 K in a dynamic mode in which
G
is determined from the change in torsional period when a field source mass is moved between two orientations. The source mass was a pair of copper rings that produced an extremely uniform gravitational field gradient, whereas the pendulum was a thin fused silica plate, a combination that minimized the measurement's sensitivity to error in pendulum placement. The measurement was made using an as-drawn CuBe torsion fibre, a heat-treated CuBe fibre, and an as-drawn Al5056 fibre. The pendulum operated with a set of different large torsional amplitudes. The three fibres yielded high
Q
-values: 82 000, 120 000 and 164 000, minimizing experimental bias from fibre anelasticity.
G
-values found with the three fibres are, respectively: {6.67435(10),6.67408(15),6.67455(13)}×10
−11
 m
3
 kg
−1
 s
−2
, with corresponding uncertainties 14, 22 and 20 ppm. Relative to the CODATA2010
G
-value, these are higher by 77, 37 and 107 ppm, respectively. The unweighted average of the three
G
-values, with the unweighted average of their uncertainties, is 6.67433(13)×10
−11
 m
3
 kg
−1
 s
−2
 (19 ppm).
Recommending a value for the Newtonian gravitational constant
Authors: Wood Barry M.
Published: September 2014

The primary objective of the CODATA Task Group on Fundamental Constants is ‘to periodically provide the scientific and technological communities with a self-consistent set of internationally recommended values of the basic constants and conversion factors of physics and chemistry based on all of the relevant data available at a given point in time’. I discuss why the availability of these recommended values is important and how it simplifies and improves science. I outline the process of determining the recommended values and introduce the principles that are used to deal with discrepant results. In particular, I discuss the specific challenges posed by the present situation of gravitational constant experimental results and how these principles were applied to the most recent 2010 recommended value. Finally, I speculate about what may be expected for the next recommended value of the gravitational constant scheduled for evaluation in 2014.
Preliminary determination of Newtonian gravitational constant with angular acceleration feedback method
Authors: Xue Chao , Quan Li-Di , Yang Shan-Qing , Wang Bing-Peng , Wu Jun-Fei , Shao Cheng-Gang , Tu Liang-Cheng , Milyukov Vadim , Luo Jun
Published: September 2014

This paper describes the preliminary measurement of the Newtonian gravitational constant
G
with the angular acceleration feedback method at HUST. The apparatus has been built, and preliminary measurement performed, to test all aspects of the experimental design, particularly the feedback function, which was recently discussed in detail by Quan
et al
. The experimental results show that the residual twist angle of the torsion pendulum at the signal frequency introduces 0.4 ppm to the value of
G
. The relative uncertainty of the angular acceleration of the turntable is approximately 100 ppm, which is mainly limited by the stability of the apparatus. Therefore, the experiment has been modified with three features: (i) the height of the apparatus is reduced almost by half, (ii) the aluminium shelves were replaced with shelves made from ultra-low expansion material and (iii) a perfect compensation of the laboratory-fixed gravitational background will be carried out. With these improvements, the angular acceleration is expected to be determined with an uncertainty of better than 10 ppm, and a reliable value of
G
with 20 ppm or below will be obtained in the near future.
The BIPM measurements of the Newtonian constant of gravitation,
G
Authors: Quinn Terry , Speake Clive , Parks Harold , Davis Richard
Published: September 2014

This paper is a complement to the two short papers published in 2001 and 2013 in which we presented the results of the two BIPM determinations of the Newtonian constant of gravitation
G
. While this review contains no new results, it includes more detailed descriptions of certain key parameters that enter into the determination of
G
. Following a description of the overall method and the two versions of the experiment, we discuss the properties of the torsion strip, including the effects of anelasticity, then the electrostatic torque transducer, the source and test masses, dimensional metrology, angle measurement, the calculation and measurement of the moment of inertia, calculation of the torque, possible magnetic interactions and finally we discuss uncertainties and correlations in the derivation of a value for
G
.
Sphingobacterium gobiense sp. nov., isolated from soil of the Gobi Desert
Authors: Zhao Peng , Zhou Zhengfu , Chen Ming , Lin Wenna , Zhang Wei , Wei Gehong
Published: September 2014

A Gram-stain-negative, short rod-shaped, non-motile, non-spore-forming bacterial strain, designated H7T, was isolated from the Gobi desert, Xinjiang Province of China. The temperature, NaCl and pH ranges for growth were 8–40 °C (optimum 30 °C), 0–5 % (w/v) NaCl and pH 6–10 (optimum pH 7), respectively. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain H7T belonged to the genus

Sphingobacterium

and showed highest sequence similarity (91 %) to

Sphingobacterium composti

DSM 18850. The genomic DNA G+C content was 44.3 mol%. MK-7 was identified as the predominant respiratory quinone. Strain H7T contained C16 : 1ω7c and/or C16 : 1ω6c, iso-C15 : 0 and iso-C17 : 0 3-OH as major fatty acids. These data support the affiliation of strain H7T to the genus

Sphingobacterium

while phenotypic data indicated it is a representative strain of a novel species for which the name Sphingobacterium
gobiense sp. nov. is proposed. The type strain is H7T ( = ACCC 05757T = KCTC 32293T).