bluuebunny/crossref_metadata_2025 huggingface dataset:
Processing and MHC class II presentation of exogenous soluble antigen involving a proteasome‐dependent cytosolic pathway in CD40‐activated B cells
Authors: Becker Hans Jiro , Kondo Eisei , Shimabukuro‐Vornhagen Alexander , Theurich Sebastian , von Bergwelt‐Baildon Michael S.
Published: November 2015

Activated B cells have the capacity to present antigen and induce immune responses as potent antigen‐presenting cells (APCs). As in other APCs, antigen presentation by B cells involves antigen internalization, antigen processing, and peptide loading onto MHC molecules. However, while the mechanism of antigen processing has been studied extensively in other APCs, this pathway remains elusive in B cells. The aim of this study was to investigate the MHC class II processing pathway in CD40‐activated B cells (CD40Bs), as a model for activated, antigen‐presenting B cells. Using CMV pp65 as a model antigen, we evaluated processing and presentation of the CD4 + T‐cell epitope 509‐523 (K509) by human CD40Bs in ELISPOT assays. As expected, stimulation of specific CD4 + T‐cell clones was attenuated after pretreatment of CD40Bs with inhibitors of classic class II pathway components. However, proteasome inhibitors such as epoxomicin limited antigen presentation as well. This suggests that the antigen is processed in a non‐classical, cytosolic MHC class II pathway. Further experiments with truncated protein variants revealed involvement of the proteasome in processing of the N and C extensions of the epitope. Access to the cytosol was shown to be size dependent. Epoxomicin sensitivity exclusively in CD40B cells, but not in dendritic cells, suggests a novel processing mechanism unique to this APC. Our data suggest that B cells process antigen using a distinct, non‐classical class II pathway.
Palmar process fractures of the distal phalanx in foals: A review
Authors: Faramarzi B. , Dobson H.
Published: November 2015

Distal phalanx fractures are well documented in adult horses, but our knowledge of such fractures in foals is limited. Recent studies showed a high incidence of distal phalanx palmar process (PP) fractures in foals, the aetiology is not yet known. Several hypotheses have been suggested as possible causes, including uneven compressive forces, unequal forces from the deep digital flexor tendon, composition and shape of the PP, and conformation. A better understanding of the aetiology and predisposing factors requires further research. Radiography is the commonly used imaging modality for diagnosis of such fractures; however, those fractures might be missed on routine radiographic projections. In order to have a high probability of identifying fractures, a series of 5 radiographs including the oblique views is required. This article reviews the incidence of distal phalanx PP fractures and discusses the diagnosis of such fractures.
Von Willebrand disease in the emergency department
Authors: Livesey K. , Yealy D. M. , Li J. , Moore C. G. , Ragni M. V.
Published: November 2015

Background

The emergency department (ED) is often the first medical contact point for von Willebrand disease (VWD) patients experiencing acute conditions, notably bleeding. However, knowledge of VWD disease types and management options by ED providers is uncertain.

Aim

To determine the scope of VWD bleeding and treatment in the ED.

Methods

We evaluated medical record data in an IRB‐approved study from 922 notes accounting for 385 ER visits by 183 VWD patients from a single large institution's emergency department.

Results

Over half the ED visits were for an active or suspected bleed, the majority of which were associated with trauma, surgery, epistaxis, gastrointestinal bleeding or gynaecologic bleeding. By treatment, only 25% of all bleeds, including 77.8% of those with menorrhagia and 50.0% of those with epistaxis, received DDAVP or von Willebrand factor concentrate (VWF). The likelihood of receiving treatment was related to referral source, with the highest rates of treatment in patients referred by a haematologist.

Conclusions

These data suggest more patient and physician education are needed in managing patients with VWD, preferably at the time of diagnosis, including confirmation of the diagnosis, response to DDAVP testing, indication for DDAVP testing and formulation of a plan for suspected or actual bleeding.
Impact of being overweight on factor VIII dosing in children with haemophilia A
Authors: Henrard S. , Hermans C.
Published: November 2015

Introduction

Treatment of haemophilia A (HA) requires infusions of factor VIII (FVIII) concentrates. The number of FVIII units infused to obtain a specific circulating FVIII level is calculated with the formula: [body weight (BW) (kg) × desired FVIII increase (%)]/2, with the assumption that each unit of FVIII infused per kg of BW increases the circulating FVIII level by 2%.

Aim

The aim of this study was to evaluate the impact of several morphometric parameters (BW, body mass index (BMI)‐for‐age, height), age and type of FVIII concentrate on FVIII recovery in children with HA.

Methods

A total of 66 children aged between 10 and 18 with severe HA selected from six pharmacokinetic (PK) clinical trials using two recombinant FVIII concentrates were included in the analysis. Regression tree (RT) was used to identify predictors of FVIII recovery.

Results

The median age was 14.5 years with a median FVIII recovery of 2.09 for all children. The median FVIII recovery was not significantly different between age groups. Two groups were created by RT: children with a BMI‐for‐age percentile <P95 (Median FVIII recovery: 1.94) and obese children with a BMI‐for‐age percentile ≥P95 (Median FVIII recovery: 2.65). The FVIII recovery was significantly different between these two groups (P < 0.001).

Conclusion

These results are consistent with previous studies conducted in adults with HA and confirm that the long‐held and current practice of applying an arbitrary and universal recovery of two to the calculations of FVIII dosage should be abolished in both children and adults.
Taxanes‐induced cutaneous eruption: another histopathologic mimicker of malignancy
Authors: Prieto‐Torres L. , Llamas‐Velasco M. , Machan S. , Haro R. , de Asis S. , Carmo M. , Loredo A. , del Puerto C. , Fried I. , Kempf W. , Cerroni L. , Requena L.
Published: November 2015

Background

Paclitaxel and docetaxel are antineoplastic drugs that bind the microtubules, producing the arrest of mitoses, which may be seen histopathologically. These histopathologic changes may simulate an intraepidermal keratinocytic malignant neoplasm, and an accurate diagnosis may be only established by clinicopathological correlation.

Objectives

We report six cases of cutaneous eruptions by taxanes in which a striking cytotoxic effect was evident histopathologically.

Methods

Cutaneous biopsies were obtained in each patient.

Results

Atypical starburst‐like or ring‐like mitoses and dyskeratosis on basal and suprabasal layers of the epidermis. Areas of squamous syringometaplasia were also seen in one case.

Discussion

These findings were interpreted as expression of mitotic arrest due to taxanes. Similar changes have been described in association with other chemotherapeutic drugs such as vincristine, podophyllin and its derivative etoposide; colchicine, busulfan and maytansine, but cases like ours due to taxanes are exceptional or under‐reported.

Conclusion

Dermatopathologists should be aware of these effects in order to interpret carefully cutaneous biopsy specimens of patients receiving taxanes.
Paternal‐specific S‐allele transmission in sweet cherry (Prunus avium L.): the potential for sexual selection
Authors: Hedhly A. , Wünsch A. , Kartal Ö. , Herrero M. , Hormaza J. I.
Published: November 2015

Homomorphic self‐incompatibility is a well‐studied example of a physiological process that is thought to increase population diversity and reduce the expression of inbreeding depression. Whereas theoretical models predict the presence of a large number of S‐haplotypes with equal frequencies at equilibrium, unequal allele frequencies have been repeatedly reported and attributed to sampling effects, population structure, demographic perturbation, sheltered deleterious mutations or selection pressure on linked genes. However, it is unclear to what extent unequal segregations are the results of gametophytic or sexual selection. Although these two forces are difficult to disentangle, testing S‐alleles in the offspring of controlled crosses provides an opportunity to separate these two phenomena. In this work, segregation and transmission of S‐alleles have been characterized in progenies of mixed donors and fully compatible pollinations under field conditions in Prunus avium. Seed set patterns and pollen performance have also been characterized. The results reveal paternal‐specific distorted transmission of S‐alleles in most of the crosses. Interestingly, S‐allele segregation within any given paternal or maternal S‐locus was random. Observations on pollen germination, pollen tube growth rate, pollen tube cohort size, seed set dynamics and transmission patterns strongly suggest post‐pollination, prezygotic sexual selection, with male–male competition as the most likely mechanism. According to these results, post‐pollination sexual selection takes precedence over frequency‐dependent selection in explaining unequal S‐haplotype frequencies.
Müller cell‐mediated neurite outgrowth of the retinal ganglion cells via P2Y6 receptor signals
Authors: Taguchi Masanori , Shinozaki Youichi , Kashiwagi Kenji , Shigetomi Eiji , Robaye Bernard , Koizumi Schuichi
Published: November 2015

Müller cells, the primary macroglia of the retina, support various functions of retinal ganglion cells (RGCs). Here, we demonstrate a nucleotide‐mediated communication between these two types of cells, by which Müller cells control neurite outgrowth of RGCs by activation of P2 receptors such as P2Y6. Cultured mouse RGCs had significantly enhanced neurite outgrowth when cultured with either cultured mouse Müller cells or conditioned medium derived from Müller cells, and this was completely inhibited by the nucleotide‐degrading enzyme, apyrase. This increase in outgrowth was mimicked by exogenously applied nucleotides such as ATP, uridine triphosphate, and uridine diphosphate. Pharmacological and genetic analysis revealed that P2Y6 receptor in RGCs was responsible for the increased neurite outgrowth. P2Y6 receptor was expressed in the ganglion cell layer of the retina and in RGC primary cultures. High performance liquid chromatography has revealed that Müller cells constitutively release uridine triphosphate, which is immediately metabolized into uridine diphosphate, an endogenous agonist for P2Y6 receptor. In the in vitro ocular hypertension model (i.e., glaucoma model), neurite outgrowth in RGCs was significantly reduced, which was associated with a decrease in P2Y6 receptors. Taken together, Müller cells control neurite outgrowth of RGCs by activating P2 receptors such as P2Y6 receptor, and the receptor expression level might be down‐regulated in glaucoma.

image

Müller cells support various functions of retina including those of retinal ganglion cells (RGCs). Here, we report an importance of nucleotide‐mediated communication between these two types of cells. Müller cells were found to release uridine diphosphate (UTD), uridine triphosphate (UTP), and activate P2Y6 receptors in RGCs, which was essential for neurite outgrowth of RGCs. In addition, P2Y6 receptors in RGCs were reduced in a glaucoma model in vitro, suggesting an involvement of their dysfunction in the pathogenesis of glaucoma.
An isoform‐specific role of FynT tyrosine kinase in Alzheimer's disease
Authors: Lee Chingli , Low Clara Y. B. , Francis Paul T. , Attems Johannes , Wong Peter T.‐H. , Lai Mitchell K.P. , Tan Michelle G.K.
Published: November 2015

Alzheimer's disease (AD) is the leading cause of dementia in old age and is characterized by the accumulation of β‐amyloid plaques and neurofibrillary tangles (NFT). Recent studies suggest that Fyn tyrosine kinase forms part of a toxic triad with β‐amyloid and tau in the disease process. However, it is not known whether Fyn is associated with the pathological features of AD in an isoform‐specific manner. In this study, we identified selective up‐regulation of the alternative‐spliced FynT isoform with no change in FynB in the AD neocortex. Furthermore, gene ontology term enrichment analyses and cell type‐specific localization of FynT immunoreactivity suggest that FynT up‐regulation was associated with neurofibrillary degeneration and reactive astrogliosis. Interestingly, significantly increased FynT in NFT‐bearing neurons was concomitant to decreased FynB immunoreactivity, suggesting an involvement of alternative splicing in NFT formation. Furthermore, cultured cells of astrocytic origin have higher FynT to FynB ratio compared to those of neuronal origin. Lastly, primary rat mixed neuron‐astrocyte cultures treated with Aβ25‐35 showed selective up‐regulation of FynT expression in activated astrocytes. Our findings point to an isoform‐specific role of FynT in modulating neurofibrillary degeneration and reactive astrogliosis in AD.

image

Fyn kinase is known to interact with β‐amyloid and tau, and contributes to Alzheimer's disease pathogenesis. In this study, it is shown that the alternatively spliced FynT isoform is specifically up‐regulated in the AD neocortex, with no change in FynB isoform. The increased FynT correlated with markers of neurofibrillary degeneration and reactive astrogliosis. In primary mixed cultures, treatment with amyloid peptides specifically up‐regulated FynT in activated astrocytes. This study points to altered alternative splicing as a potential pathogenic mechanism in AD.
Phosphorylation of CaMKII in the rat dorsal raphe nucleus plays an important role in sleep–wake regulation
Authors: Cui Su‐Ying , Li Sheng‐Jie , Cui Xiang‐Yu , Zhang Xue‐Qiong , Yu Bin , Sheng Zhao‐Fu , Huang Yuan‐Li , Cao Qing , Xu Ya‐Ping , Lin Zhi‐Ge , Yang Guang , Song Jin‐Zhi , Ding Hui , Wang Zi‐Jun , Zhang Yong‐He
Published: November 2015

The Ca2+ modulation in the dorsal raphe nucleus (DRN) plays an important role in sleep–wake regulation. Calmodulin‐dependent kinase II (CaMKII) is an important signal‐transducing molecule that is activated by Ca2+. This study investigated the effects of intracellular Ca2+/CaMKII signaling in the DRN on sleep–wake states in rats. Maximum and minimum CaMKII phosphorylation was detected at Zeitgeber time 21 (ZT 21; wakefulness state) and ZT 3 (sleep state), respectively, across the light–dark rhythm in the DRN in rats. Six‐hour sleep deprivation significantly reduced CaMKII phosphorylation in the DRN. Microinjection of the CAMKII activation inhibitor KN‐93 (5 or 10 nmol) into the DRN suppressed wakefulness and enhanced rapid‐eye‐movement sleep (REMS) and non‐REM sleep (NREMS). Application of a high dose of KN‐93 (10 nmol) increased slow‐wave sleep (SWS) time, SWS bouts, the mean duration of SWS, the percentage of SWS relative to total sleep, and delta power density during NREMS. Microinjection of CaCl2 (50 nmol) in the DRN increased CaMKII phosphorylation and decreased NREMS, SWS, and REMS. KN‐93 abolished the inhibitory effects of CaCl2 on NREMS, SWS, and REMS. These data indicate a novel wake‐promoting and sleep‐suppressing role for the Ca2+/CaMKII signaling pathway in DRN neurons.

image

We propose that the intracellular Ca2+/CaMKII signaling in the dorsal raphe nucleus (DRN) plays wake‐promoting and sleep‐suppressing role in rats. Intra‐DRN application of KN‐93 (CaMKII activation inhibitor) suppressed wakefulness and enhanced rapid‐eye‐movement sleep (REMS) and non‐REMS (NREMS). Intra‐DRN application of CaCl2 attenuated REMS and NREMS. We think these findings should provide a novel cellular and molecular mechanism of sleep–wake regulation.
Construct validity of the Free and Cued Selective Reminding Test in older adults with memory complaints
Authors: Clerici Francesca , Ghiretti Roberta , Di Pucchio Alessandra , Pomati Simone , Cucumo Valentina , Marcone Alessandra , Vanacore Nicola , Mariani Claudio , Cappa Stefano Francesco
Published: November 2015

Introduction

The Free and Cued Selective Reminding Test (FCSRT) is the memory test recommended by the International Working Group on Alzheimer's disease (AD) for the detection of amnestic syndrome of the medial temporal type in prodromal AD. Assessing the construct validity and internal consistency of the Italian version of the FCSRT is thus crucial.

Methods

The FCSRT was administered to 338 community‐dwelling participants with memory complaints (57% females, age 74.5 ± 7.7 years), including 34 with AD, 203 with Mild Cognitive Impairment, and 101 with Subjective Memory Impairment. Internal Consistency was estimated using Cronbach's alpha coefficient. To assess convergent validity, five FCSRT scores (Immediate Free Recall, Immediate Total Recall, Delayed Free Recall, Delayed Total Recall, and Index of Sensitivity of Cueing) were correlated with three well‐validated memory tests: Story Recall, Rey Auditory Verbal Learning test, and Rey Complex Figure (RCF) recall (partial correlation analysis). To assess divergent validity, a principal component analysis (an exploratory factor analysis) was performed including, in addition to the above‐mentioned memory tasks, the following tests: Word Fluencies, RCF copy, Clock Drawing Test, Trail Making Test, Frontal Assessment Battery, Raven Coloured Progressive Matrices, and Stroop Colour‐Word Test.

Results

Cronbach's alpha coefficients for immediate recalls (IFR and ITR) and delayed recalls (DFR and DTR) were, respectively, .84 and .81. All FCSRT scores were highly correlated with those of the three well‐validated memory tests. The factor analysis showed that the FCSRT does not load on the factors saturated by non‐memory tests.

Conclusions

These findings indicate that the FCSRT has a good internal consistency and has an excellent construct validity as an episodic memory measure.
Social Skills Use of International Students in Japan
Authors: Tanaka Tomoko , Okunishi Yuri
Published: November 2015

This study investigated the cross‐cultural social skills use of international students in Japan. One hundred and forty questionnaires were sent out and 102 were returned. Participants evaluated their skills use with 21 items pertaining to cross‐cultural social skills in Japan, which were considered useful in forming interpersonal relationships with their Japanese hosts. They also evaluated how common such skills were in their own countries. The skills were divided into the following four categories: (a) skills used in Japan and recognized as being used in home countries, which seemed to be applications of original behavior repertory (Maintained skills); (b) skills used in Japan but not recognized in their own countries, which seemed to be developed in the Japanese sociocultural context (Acquired skills); (c) skills recognized in their home countries but not used in Japan, which seemed to be somehow suppressed in Japan (Avoided skills); and (d) skills rarely used in Japan and rarely recognized in their home countries, which seemed to be undesired (Neglected skills). Some skills were relatively common in their own countries but not always highly used in Japan. Students with higher Japanese proficiency or a longer duration of stay in Japan tended to show higher skills use. However, the assumption that students from neighboring countries were more skillful was not supported. The psychological background of cross‐cultural social skills use was also discussed.
Testicular Functions and Clinical Characterization of Patients with Gender Dysphoria (GD) Undergoing Sex Reassignment Surgery (SRS)
Authors: Schneider Florian , Neuhaus Nina , Wistuba Joachim , Zitzmann Michael , Heß Jochen , Mahler Dorothee , van Ahlen Hermann , Schlatt Stefan , Kliesch Sabine
Published: November 2015

Introduction

Cross-sex hormone treatment of gender dysphoria (GD) patients changing from male to female a prerequisite for sex reassignment. For initial physical adaptation, a combined treatment of anti-androgens and estrogens is used. Provided that patients fulfill specific criteria, sex reassignment surgery (SRS) presents the final step toward physical adaptation. However, systematic studies analyzing effects of hormone treatment regimens are lacking.

Aim

The aim of this study was to compare the effects of three different hormonal treatment strategies regarding endocrinological parameters and testicular histology.

Methods

Testicular tissues were obtained in a multicenter study from 108 patients on the day of SRS from three clinics following different treatment strategies. Patients either discontinued treatment 6 weeks (clinic A) or 2 weeks (clinic B) prior to SRS or not at all (clinic C). Testicular tissues, ethylenediaminetetraacetic acid blood and questionnaires were obtained on the day of SRS.

Main Outcome Measures

Blood hormone and intratesticular testosterone (ITT) levels were measured. Testicular weight and histology were evaluated and the percentage of luteinizing hormone/choriogonadotropin receptor (LHCGR) positive cells was determined.

Results

According to the questionnaires, patients showed desired phenotypical changes including breast growth (75%) and smooth skin (32%). While patients from clinics A and B presented with rather virilized hormonal levels, patients from clinic C showed generally feminized blood serum levels. Histological evaluation revealed highly heterogeneous results with about 24% of patients presenting with qualitatively normal spermatogenesis. In accordance with serum endocrine profile, ITT levels were lowest in clinic C and correlated with testosterone and free testosterone, but not with the spermatogenic state. The percentage of LHCGR-positive cells and ITT levels did not correlate.

Conclusion

Only patients that did not discontinue hormonal treatment showed feminized blood levels on the day of SRS. The ones who stopped re-virilized quickly. Interestingly, testicular histology was highly heterogeneous irrespective of the treatment strategy, a phenomenon that requires further investigation.
Genomic resources and their influence on the detection of the signal of positive selection in genome scans
Authors: Manel S. , Perrier C. , Pratlong M. , Abi‐Rached L. , Paganini J. , Pontarotti P. , Aurelle D.
Published: November 2015

Genome scans represent powerful approaches to investigate the action of natural selection on the genetic variation of natural populations and to better understand local adaptation. This is very useful, for example, in the field of conservation biology and evolutionary biology. Thanks to Next Generation Sequencing, genomic resources are growing exponentially, improving genome scan analyses in non‐model species. Thousands of SNPs called using Reduced Representation Sequencing are increasingly used in genome scans. Besides, genome sequences are also becoming increasingly available, allowing better processing of short‐read data, offering physical localization of variants, and improving haplotype reconstruction and data imputation. Ultimately, genome sequences are also becoming the raw material for selection inferences. Here, we discuss how the increasing availability of such genomic resources, notably genome sequences, influences the detection of signals of selection. Mainly, increasing data density and having the information of physical linkage data expand genome scans by (i) improving the overall quality of the data, (ii) helping the reconstruction of demographic history for the population studied to decrease false‐positive rates and (iii) improving the statistical power of methods to detect the signal of selection. Of particular importance, the availability of a high‐quality reference genome can improve the detection of the signal of selection by (i) allowing matching the potential candidate loci to linked coding regions under selection, (ii) rapidly moving the investigation to the gene and function and (iii) ensuring that the highly variable regions of the genomes that include functional genes are also investigated. For all those reasons, using reference genomes in genome scan analyses is highly recommended.
TcpM: a novel relaxase that mediates transfer of large conjugative plasmids from Clostridium perfringens
Authors: Wisniewski Jessica A. , Traore Daouda A. , Bannam Trudi L. , Lyras Dena , Whisstock James C. , Rood Julian I.
Published: November 2015

Conjugative transfer of toxin and antibiotic resistance plasmids in Clostridium perfringens is mediated by the tcp conjugation locus. Surprisingly, neither a relaxase gene nor an origin of transfer (oriT) has been identified on these plasmids, which are typified by the 47 kb tetracycline resistance plasmid pCW3. The tcpM gene (previously called intP) encodes a potential tyrosine recombinase that was postulated to be an atypical relaxase. Mutagenesis and complementation studies showed that TcpM was required for wild‐type transfer of pCW3 and that a tyrosine residue, Y259, was essential for TcpM activity, which was consistent with the need for a relaxase‐mediated hydrophilic attack at the oriT site. Other catalytic residues conserved in tyrosine recombinases were not required for TcpM activity, suggesting that TcpM was not a site‐specific recombinase. Mobilization studies led to the identification of the oriT site, which was located in the 391 bp intergenic region upstream of tcpM. The oriT site was localized to a 150 bp region, and gel mobility shift studies showed that TcpM could bind to this region. Based on these studies we postulate that conjugative transfer of pCW3 involves the atypical relaxase TcpM binding to and processing the oriT site to initiate plasmid transfer.
Novel features of the ISC machinery revealed by characterization of Escherichia coli mutants that survive without iron–sulfur clusters
Authors: Tanaka Naoyuki , Kanazawa Miaki , Tonosaki Keitaro , Yokoyama Nao , Kuzuyama Tomohisa , Takahashi Yasuhiro
Published: November 2015

Biological assembly of iron–sulfur (Fe–S) clusters is mediated by complex systems consisting of multiple proteins. Escherichia coli possesses two distinct systems called the ISC and SUF machineries encoded by iscSUA‐hscBA‐fdx‐iscX and sufABCDSE respectively. Deletion of both pathways results in absence of the biosynthetic apparatus for Fe–S clusters, and consequent lethality, which has hampered detailed genetic studies. Here we report that modification of the isoprenoid biosynthetic pathway can offset the indispensability of the Fe–S cluster biosynthetic systems and show that the resulting Δisc Δsuf double mutants can grow without detectable Fe–S cluster‐containing proteins. We also constructed a series of mutants in which each isc gene was disrupted in the deletion background of sufABCDSE. Phenotypic analysis of the mutants revealed that Fdx, an essential electron‐transfer Fe–S protein in the ISC machinery, is dispensable under anaerobic conditions, which is similar to the situation with IscA. Furthermore, we found that several suppressor mutations in IscU, an Fe–S scaffold protein responsible for the de novo Fe–S cluster assembly, could bypass the essential role of the chaperone system HscA and HscB. These findings pave the way toward a detailed molecular analysis to understand the mechanisms involved in Fe–S cluster biosynthesis.
Escherichia coli ClbS is a colibactin resistance protein
Authors: Bossuet‐Greif Nadège , Dubois Damien , Petit Claude , Tronnet Sophie , Martin Patricia , Bonnet Richard , Oswald Eric , Nougayrède Jean‐Philippe
Published: November 2015

The genomic pks island codes for the biosynthetic machinery that produces colibactin, a peptide‐polyketide metabolite. Colibactin is a genotoxin that contributes to the virulence of extra‐intestinal pathogenic Escherichia coli and promotes colorectal cancer. In this work, we examined whether the pks‐encoded clbS gene of unknown function could participate in the self‐protection of E. coli‐producing colibactin. A clbS mutant was not impaired in the ability to inflict DNA damage in HeLa cells, but the bacteria activated the SOS response and ceased to replicate. This autotoxicity phenotype was markedly enhanced in a clbS uvrB double mutant inactivated for DNA repair by nucleotide excision but was suppressed in a clbS clbA double mutant unable to produce colibactin. In addition, ectopic expression of clbS protected infected HeLa cells from colibactin. Thus, ClbS is a resistance protein blocking the genotoxicity of colibactin both in the procaryotic and the eucaryotic cells.
Time to talk about work‐hour impact on anesthesiologists
Authors: Saadat Haleh , Bissonnette Bruno , Tumin Dmitry , Thung Arlyne , Rice Julie , Barry N'Diris , Tobias Joseph
Published: November 2015

Background

A physician's fatigue raises significant concerns regarding personal and patient safety. Effects of sleep deprivation on clinical performance and the quality of patient care are major considerations of today's health care environment.

Aim

To evaluate the impact of partial sleep deprivation after a 17‐h overnight call (3 pm–7 am) on the mood status and cognitive skills of anesthesiologists in an academic clinical hospital setting, as compared to these parameters during regular working hours.

Methods

Taking circadian rhythm into account, the following measures were assessed in 21 pediatric anesthesiologists at two time points over the course of the study; (i) between 7 and 8 am on a regular non call day, and (ii) between 7 and 8 am after a 17‐h in‐house call (3 pm–7 am). Six mood states were assessed using the Profile of Mood States. A Total Mood Disturbance (TMD) score was obtained as the sum of all mood scores minus vigor. The total score provides a global estimate of affective state. Simple cognitive tests were similarly administered to assess cognitive skills. A two‐tailed paired t‐test was used to compare data between regular and post call days. A P < 0.05 was used.

Results

The study cohort included 21 pediatric anesthesiologists at a tertiary care children's hospital. Tension, anger, fatigue, confusion, TMD, irritability, feeling jittery, and sleepiness were significantly affected (P < 0.05). A decrease in vigor, energy, and confidence was observed after a night call shift (P < 0.05). There was also a decrease in being “talkative” after the call shift (P < 0.05).

Conclusion

Partial sleep deprivation affects the total mood status of anesthesiologists and impacts their cognitive skills. These findings are particularly relevant in a context of increased work expectation, particularly on clinical performance in our modern medical system. Such observations suggest that there may be changes that impact the safety of our patients and the quality of health care that is provided.
Structured intervention for management of pain following day surgery in children
Authors: Walther‐Larsen Søren , Aagaard Gitte Bruun , Friis Susanne Molin , Petersen Trine , Møller‐Sonnergaard Jørn , Rømsing Janne
Published: November 2015

Summery

Background

Ambulatory surgery forms a large part of pediatric surgical practice. Several studies indicate that postoperative pain is poorly managed with more than 30% of children having moderate to severe pain. In a busy outpatient clinic contact between healthcare professionals and the family is increasingly limited calling for a global and efficient pain management regime.

Objective

The aim of this prospective observational cohort study was to determine postoperative pain intensity following day surgery in children after our structured intervention for pain management.

Methods

A number of interventions in an effort to address barriers to effective postoperative pain management after day surgery were identified in the literature. By introducing our concept structured intervention, we aimed to address the majority if not all these barriers. Accordingly, we adapted postoperative pain management to each child using a multimodal approach consisting of surgery‐specific analgesia with weight appropriate doses of acetaminophen and ibuprofen. Analgesics were handed out to the parents in formulations accepted by child and parent and after thorough information to the parents.

Results

Two hundred and forty‐five children were scheduled for surgery during the 3‐month period of which 149 children were available for analysis. The postoperative pain as assessed by the parents with a the Short Form of the Parents' Postoperative Pain Measure (PPPM‐SF) was well managed exhibiting a median pain score of 4 on postoperative day 0 (POD0) and median 1 on postoperative day 1 (POD1) and a numeric rating scale (NRS) median pain score of 2 on POD0 and median 1 on POD1. We found a highly significant correlation between the PPPM‐SF and the NRS scores.

Conclusion

After thorough information of the parents we have successfully implemented a surgery‐specific regime of primarily around‐the‐clock dosing of drug formulations acceptable for the specific child with dispensed medication ready available for the family.
Both foliar and residual applications of herbicides that inhibit amino acid biosynthesis induce alternative respiration and aerobic fermentation in pea roots
Authors: Armendáriz O. , Gil‐Monreal M. , Zulet A. , Zabalza A. , Royuela M.
Published: November 2015

The objective of this work was to ascertain whether there is a general pattern of carbon allocation and utilisation in plants following herbicide supply, independent of the site of application: sprayed on leaves or supplied to nutrient solution. The herbicides studied were the amino acid biosynthesis‐inhibiting herbicides (ABIH): glyphosate, an inhibitor of aromatic amino acid biosynthesis, and imazamox, an inhibitor of branched‐chain amino acid biosynthesis. All treated plants showed impaired carbon metabolism; carbohydrate accumulation was detected in both leaves and roots of the treated plants. The accumulation in roots was due to lack of use of available sugars as growth was arrested, which elicited soluble carbohydrate accumulation in the leaves due to a decrease in sink strength. Under aerobic conditions, ethanol fermentative metabolism was enhanced in roots of the treated plants. This fermentative response was not related to a change in total respiration rates or cytochrome respiratory capacity, but an increase in alternative oxidase capacity was detected. Pyruvate accumulation was detected after most of the herbicide treatments. These results demonstrate that both ABIH induce the less‐efficient, ATP‐producing pathways, namely fermentation and alternative respiration, by increasing the key metabolite, pyruvate. The plant response was similar not only for the two ABIH but also after foliar or residual application.
Gene mapping and functional analysis of the novel leaf color gene SiYGL1 in foxtail millet [Setaria italica (L.) P. Beauv]
Authors: Li Wen , Tang Sha , Zhang Shuo , Shan Jianguo , Tang Chanjuan , Chen Qiannan , Jia Guanqing , Han Yuanhuai , Zhi Hui , Diao Xianmin
Published: November 2015

Setaria italica and its wild ancestor Setaria viridis are emerging as model systems for genetics and functional genomics research. However, few systematic gene mapping or functional analyses have been reported in these promising C4 models. We herein isolated the yellow‐green leaf mutant (siygl1) in S. italica using forward genetics approaches. Map‐based cloning revealed that SiYGL1, which is a recessive nuclear gene encoding a magnesium‐chelatase D subunit (CHLD), is responsible for the mutant phenotype. A single Phe to Leu amino acid change occurring near the ATPase‐conserved domain resulted in decreased chlorophyll (Chl) accumulation and modified chloroplast ultrastructure. However, the mutation enhanced the light‐use efficiency of the siygl1 mutant, suggesting that the mutated CHLD protein does not completely lose its original activity, but instead, gains novel features. A transcriptional analysis of Chl a oxygenase revealed that there is a strong negative feedback control of Chl b biosynthesis in S. italica. The SiYGL1 mRNA was expressed in all examined tissues, with higher expression observed in the leaves. Comparison of gene expression profiles in wild‐type and siygl1 mutant plants indicated that SiYGL1 regulates a subset of genes involved in photosynthesis (rbcL and LHCB1), thylakoid development (DEG2) and chloroplast signaling (SRP54CP). These results provide information regarding the mutant phenotype at the transcriptional level. This study demonstrated that the genetic material of a Setaria species could be ideal for gene discovery investigations using forward genetics approaches and may help to explain the molecular mechanisms associated with leaf color variation.
Early dysautonomia detected by heart rate variability predicts late depression in female patients following mild traumatic brain injury
Authors: Sung Chih‐Wei , Lee Hsin‐Chien , Chiang Yung‐Hsiao , Chiu Wen‐Ta , Chu Shu‐Fen , Ou Ju‐Chi , Tsai Shin‐Han , Liao Kuo‐Hsing , Lin Chien‐Min , Lin Jia‐Wei , Chen Gunng‐Shinng , Li Wei‐Jiun , Wang Jia‐Yi
Published: November 2015

Depression is one of the frequent complications following a mild traumatic brain injury (mTBI). Recent research indicated that abnormalities in the autonomic nervous system (ANS) can be evaluated by a noninvasive power spectral analysis of the heart rate variability (HRV). In this study, we investigated whether a frequency‐domain analysis of HRV was correlated with late depression in mTBI patients. In total, 181 patients diagnosed with mTBI and 83 volunteers as healthy controls were recruited in 2010–2014. Beck Depression Inventory (BDI) scores were used to evaluate depression in the 1st week of assessment and at 1.5‐, 3‐, 6‐, 12‐, and 18‐month follow‐ups. Correlation and logistic regression analyses of the 1st week HRV parameters with BDI scores at 18 months were performed in individual female mTBI patients. Female mTBI patients were more vulnerable to depression accompanied by reduced HRV compared to healthy controls. Over time, depression was aggravated in female mTBI patients but was alleviated in male mTBI patients. A significantly lower parasympathetic proportion of the ANS was noted at 18 months with respect to the 1st week in female mTBI patients. In addition, depression in female mTBI patients at 18 months after injury was significantly correlated with a decrease in the parasympathetic proportion of the ANS in the 1st week (ρ = −0.411; p < .05). Dysautonomia resulted in higher risks of depression in female mTBI patients. We concluded that early dysautonomia following an mTBI contributes to late depression in female mTBI patients.
Changing physical activity and sedentary behaviour in people with COPD
Authors: Cavalheri Vinicius , Straker Leon , Gucciardi Daniel F. , Gardiner Paul A. , Hill Kylie
Published: November 2015

People with chronic obstructive pulmonary disease (COPD) engage in low levels of physical activity (PA). Given the evidence for the health benefits associated with participating in 150 min of moderate‐to‐vigorous intensity PA each week, there is considerable interest in methods to increase PA in people with COPD. Studies to date have focused largely on exercise training and behavioural approaches, and many have demonstrated minimal, if any effect. An intermediate goal that focuses on reducing time spent in sedentary behaviour (SB) and increasing participation in light intensity PA is a more realistic goal in this population and offers a gateway to higher intensity PA. Although strategies that are capable of reducing time spent in SB in COPD are unknown, studies that have shown some increase in PA in this population often provide individualized goal setting, motivational interviewing and frequent contact with health‐care professionals to provide advice regarding strategies to overcome barriers. Therefore, these approaches should be considered in interventions to reduce time in SB. There are a range of devices available to monitor time in SB for use in both clinical and research settings. To move this area forward, a theoretically informed and systematic approach to behaviour change is needed. The theoretical model, the ‘behaviour change wheel’, is described and an example is provided of how it can be applied to a person with COPD.
Effects of low‐dose morphine on perceived sleep quality in patients with refractory breathlessness: A hypothesis generating study
Authors: Martins Rodrigo T. , Currow David C. , Abernethy Amy P. , Johnson Miriam J. , Toson Barbara , Eckert Danny J.
Published: November 2015

Background and objective

The management of chronic refractory breathlessness is one of the indications for regular low‐dose (≤30 mg/24 h) oral sustained release morphine. Morphine may disrupt sleep in some conditions and improve sleep quality in others. This study aimed to determine any signal of regular, low‐dose morphine on perceived sleep disruption due to breathlessness and perceived sleep quality.

Methods

This is a secondary analysis of data from 38 participants with refractory breathlessness (30 male; 33 with COPD) aged 76 ± 0.9 years who completed a double‐blind, randomized, placebo‐controlled, cross‐over study in which they received 20 mg oral sustained release morphine daily and placebo for 4 days each. Participant ratings of sleep disruption due to breathlessness and perceived sleep quality were obtained daily throughout the 8‐day trial.

Results

Perceived sleep disruption due to breathlessness over the 4‐day period ranged between 13% and 32% of participants for placebo and 13% and 26% for morphine, decreasing by each day of the study during the morphine arm. Most participants reported ‘very good’ or ‘quite good’ sleep throughout the trial and were less likely to perceive poor sleep quality during the morphine arm (odds ratio = 0.55, 95% confidence interval: 0.34–0.88, P = 0.01). Participants who reported decreased breathlessness during the 4 days on morphine were also likely to report improved sleep quality with morphine (P = 0.039).

Conclusion

Four days of low‐dose morphine improved perceived sleep quality in elderly participants with refractory breathlessness. Regular low‐dose morphine targeted to reduce refractory breathlessness may yield associated benefits by reducing sleep disruption and improving sleep quality.
Suppressing methane emission and global warming potential from rice fields through intermittent drainage and green biomass amendment
Authors: Haque Md. M. , Biswas J. C. , Kim S. Y. , Kim P. J.
Published: November 2015

Winter cover crops are recommended to improve soil quality and carbon sequestration, although their use as green manure can significantly increase methane (CH4) emission from paddy soils. Soil management practices can be used to reduce CH4 emission from paddy soils, but intermittent drainage is regarded as a key practice to reduce CH4 emission and global warming potential (GWP). However, significantly greater emissions of carbon dioxide (CO2) and nitrous oxide (N2O) are expected when large amounts of cover crop biomass are incorporated into soils. In this study, we investigated the effects of midseason drainage on CH4 emission and GWP following incorporation of 0, 3, 6 and 12 Mg/ha of cover crop biomass. Methane, CO2 and N2O emission rates significantly (P < 0.05) increased with higher rates of cover crop biomass incorporation under both irrigation conditions. However, intermittent drainage effectively reduced seasonal CH4 fluxes by ca. 42–46% and GWP by 17–31% compared to continuous flooding. Moreover, there were no significant differences in rice yield between the two water management practices with similar biomass incorporation rates. In conclusion, intermittent drainage and incorporation of 3 Mg/ha of green biomass could be a good management option to reduce GWP.
Room temperature plasma enhanced atomic layer deposition for TiO2 and WO3 films
Authors: Strobel Alexander , Schnabel Hans-Dieter , Reinhold Ullrich , Rauer Sebastian , Neidhardt Andreas
Published: November 2015

This paper presents a study on plasma enhanced atomic layer deposition (ALD) of TiO2 and WO3 films on silicon substrates. At low temperatures, ALD processes, which are not feasible at high temperatures, could be possible. For example, temperatures at 180 °C and above allow no WO3 ALD process with WF6 as a precursor because etching processes hinder film growth. Further low temperature deposition techniques are needed to coat temperature sensitive materials. For the deposition, WF6 and TiCl4 are used as metal precursors and O2 and H2O as oxygen sources. The depositions were accomplished in the temperature range of 30 °C up to 180 °C for both metal oxides. Spectroscopic ellipsometry, x-ray reflection, and grazing incidence diffraction were used to investigate the deposited ALD thin films. Film growth, density, crystallinity, and roughness are discussed as functions of temperature after ensuring the ALD requirement of self-saturating adsorption. Growth rates and measured material properties are in good agreement with literature data.
Enhanced adhesion of electron beam resist by grafted monolayer poly(methylmethacrylate-co-methacrylic acid) brush
Authors: Viscomi Francesco Narda , Dey Ripon Kumar , Caputo Roberto , Cui Bo
Published: November 2015

In electron beam lithography, poor resist adhesion to a substrate may lead to resist structure detachment upon development. One popular method to promote resist adhesion is to modify the substrate surface. In this study, the authors will show that a poly(methylmethacrylate-co-methacrylic acid) [P(MMA-co-MAA)] monolayer “brush” can be grafted onto a silicon substrate using thermal annealing that leads to chemical bonding of the P(MMA-co-MAA) copolymer to the hydroxyl group-terminated substrate, followed by acetic acid wash to remove the bulk, unbonded copolymer. The monolayer brush has a thickness of 12 nm. The authors will show that it can greatly improve the adhesion of positive resist, the ZEP-520A, and negative resist polystyrene to bare silicon surfaces, which led to high resolution patterning without resist detachment upon development. The improvement was more dramatic when patterning dense sub-100 nm period grating structures. But the improvement was negligible for an aluminum substrate, because, even without the brush layer, resist adhesion to aluminum is found already to be strong enough to prevent resist structure peeling off. The current simple and low cost method could be very useful when resist adhesion to the substrate for a given developer is weak.
High resolution 3D imaging of synchrotron generated microbeams
Authors: Gagliardi Frank M. , Cornelius Iwan , Blencowe Anton , Franich Rick D. , Geso Moshi
Published: November 2015

Purpose:

Microbeam radiation therapy (MRT) techniques are under investigation at synchrotrons worldwide. Favourable outcomes from animal and cell culture studies have proven the efficacy of MRT. The aim of MRT researchers currently is to progress to human clinical trials in the near future. The purpose of this study was to demonstrate the high resolution and 3D imaging of synchrotron generated microbeams in PRESAGE® dosimeters using laser fluorescence confocal microscopy.

Methods:

Water equivalent PRESAGE® dosimeters were fabricated and irradiated with microbeams on the Imaging and Medical Beamline at the Australian Synchrotron. Microbeam arrays comprised of microbeams 25–50 μm wide with 200 or 400 μm peak‐to‐peak spacing were delivered as single, cross‐fire, multidirectional, and interspersed arrays. Imaging of the dosimeters was performed using a nikon a1 laser fluorescence confocal microscope.

Results:

The spatial fractionation of the MRT beams was clearly visible in 2D and up to 9 mm in depth. Individual microbeams were easily resolved with the full width at half maximum of microbeams measured on images with resolutions of as low as 0.09 μm/pixel. Profiles obtained demonstrated the change of the peak‐to‐valley dose ratio for interspersed MRT microbeam arrays and subtle variations in the sample positioning by the sample stage goniometer were measured.

Conclusions:

Laser fluorescence confocal microscopy of MRT irradiated PRESAGE® dosimeters has been validated in this study as a high resolution imaging tool for the independent spatial and geometrical verification of MRT beam delivery.