bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel G6B gene variant causes familial autosomal recessive thrombocytopenia and anemia
Authors: Melhem Motasem , Abu‐Farha Mohamed , Antony Dinu , Madhoun Ashraf Al , Bacchelli Chiara , Alkayal Fadi , AlKhairi Irina , John Sumi , Alomari Mohamad , Beales Phillip L. , Alsmadi Osama
Published: October 2016

Objective

To characterize the underlying genetic and molecular defects in a consanguineous family with lifelong blood disorder manifested with thrombocytopenia (low platelets count) and anemia.

Methods

Genetic linkage analysis, exome sequencing, and functional genomics were carried out to identify and characterize the defective gene.

Results

We identified a novel truncation mutation (p.C108*) in chromosome 6 open reading frame 25 (C6orf25) gene in this family. We also showed the p.C108* mutation was responsible for destabilizing the encoded truncated G6B protein. Unlike the truncated form, wild‐type G6B expression resulted in enhanced K562 differentiation into megakaryocytes and erythrocytes. C6orf25, also known as G6B, is an effector protein for the key hematopoiesis regulators, Src homology region 2 domain‐containing phosphatases SHP‐1 and SHP‐2.

Conclusion

G6B seems to act through an autosomal recessive mode of disease transmission in this family and regarded as the gene responsible for the observed hematological disorder. This inference is well supported further by in vivo evidence where similar outcomes were reported from G6b−/− and SHP1/2 DKO mouse models.
Market Risk Disclosures and Investment Efficiency: International Evidence from the Gulf Cooperation Council Financial Firms
Authors: Al‐Hadi Ahmed , Hasan Mostafa Monzur , Taylor Grantley , Hossain Mahmud , Richardson Grant
Published: October 2016

This study examines the association between market risk disclosures (MRDs) and the investment efficiency of financial firms from six emerging markets in the Gulf Cooperation Council (GCC) region. Based on a sample of 553 firm‐year observations over the 2007–2011 period, we find that MRDs are significantly and negatively associated with both under‐investment and over‐investment and that this association is more pronounced for larger firms. We also find that the association between MRDs and under‐investment is moderated during periods of economic distress such as the Global Financial Crisis of 2008 and that the association between MRDs and over‐investment is magnified during periods of reduced financial distress. Our results are consistent with the idea that MRDs reduce information asymmetry, which ultimately improves investment efficiency. We contribute to the literature in an emerging market context by providing empirical evidence on the association between MRDs and investment efficiency across six emerging GCC capital markets. This study also fills a gap in the literature by providing evidence on the factors affecting the investment efficiency of financial firms.
THE EMPIRICS OF THE MUNICIPAL FISCAL ADJUSTMENT
Authors: Martin‐Rodriguez Maria , Ogawa Hikaru
Published: October 2016

We summarize the literature that uses the vector error‐correction model approach to analyze the dynamics of the municipal fiscal adjustment. The international comparison between samples collected from entire countries and specific regions reveals interesting similarities, but also remarkable differences. The main similarities are the fulfillment of the intertemporal budget constraint, the volatility of the budgetary components, and the importance of the intergovernmental transfers as an adjustment instrument. The most remarkable difference is the preponderant role of the own revenues in the USA, probably reflecting the larger fiscal autonomy of US municipalities. In most cases, the large municipalities seem to be more dependent on grants than their small counterparts, although this pattern is broken in Japan. Finally, partial evidence supporting the existence of moral hazard problems and the flypaper effect is provided.
Blood oxygenation of masseter muscle during sustained elevated muscle activity in healthy participants
Authors: Suzuki S. , Castrillon E. E. , Arima T. , Kitagawa Y. , Svensson P.
Published: October 2016

Myofascial pain associated with temporomandibular disorders has often been linked to pathological muscle hyperactivity. As a result, localised disturbances of intramuscular blood flow could lead to a lower level of oxygen distribution, hypoxia and microcirculatory changes. To assess haemodynamic changes in the masseter muscle during sustained elevated muscle activity (SEMA). Sixteen healthy participants performed thirty 1‐min bouts of SEMA with intervals of 1‐min ‘rest’ periods between the bouts on a bite force transducer device. The participants completed three sessions with different percentage of their maximal voluntary occlusal bite force (MVOBF): 0% (no task), 10% or 40% MVOBF tasks. The order of the sessions was randomised with 1‐ to 2‐week intervals. Haemodynamic characteristics of the masseter muscle were estimated with use of a laser blood oxygenation monitor. Tissue blood oxygen saturation (StO2) during SEMA was lower than during rest (P < 0·001). The relative changes in total haemoglobin (Total‐Hb) and StO2 were influenced by condition (SEMA and rest) and with interactions between condition and session (0%, 10% and 40% MVOBF tasks). These results suggest that SEMA may lead to hypoxia in the masseter muscle and that the haemodynamic characteristics and muscle symptoms depend on the magnitude of muscle contractions. Overall, the present findings may help to provide better insights into relationships between jaw muscle activity, haemodynamic changes and symptom developments with implications for clinical conditions such as bruxism characterised by different levels of tooth‐grinding and tooth‐clenching muscle activity.
Plasticity of archaeal C/D box sRNA biogenesis
Authors: Tripp Vanessa , Martin Roman , Orell Alvaro , Alkhnbashi Omer S. , Backofen Rolf , Randau Lennart
Published: October 2016

Archaeal and eukaryotic organisms contain sets of C/D box s(no)RNAs with guide sequences that determine ribose 2′‐O‐methylation sites of target RNAs. The composition of these C/D box sRNA sets is highly variable between organisms and results in varying RNA modification patterns which are important for ribosomal RNA folding and stability. Little is known about the genomic organization of C/D box sRNA genes in archaea. Here, we aimed to obtain first insights into the biogenesis of these archaeal C/D box sRNAs and analyzed the genetic context of more than 300 archaeal sRNA genes. We found that the majority of these genes do not possess independent promoters but are rather located at positions that allow for co‐transcription with neighboring genes and their start or stop codons were frequently incorporated into the conserved boxC and D motifs. The biogenesis of plasmid‐encoded C/D box sRNA variants was analyzed in vivo in Sulfolobus acidocaldarius. It was found that C/D box sRNA maturation occurs independent of their genetic context and relies solely on the presence of intact RNA kink‐turn structures. The observed plasticity of C/D box sRNA biogenesis is suggested to enable their accelerated evolution and, consequently, allow for adjustments of the RNA modification landscape.
Physical activity and obesity: what we know and what we need to know*
Authors: Chin S.‐H. , Kahathuduwa C. N. , Binks M.
Published: October 2016

Creating a negative energy balance by decreasing caloric consumption and increasing physical activity is a common strategy used to treat obesity. A large number of review and original research papers have considered the role of physical activity in weight loss and maintenance. However, their conclusions are at times conflicting. In this review, we have critically evaluated the findings of systematic reviews and meta‐analyses and supplemented their conclusions with recently published, high‐quality clinical trials. We have eliminated studies that were methodologically flawed in an attempt to reduce the ambiguity in the literature. We further sought, through selective review of these publications, to isolate the effects of various types of exercise, independent of dietary interventions, to further clarify their independent contributions. Thus, our review describes (i) combined calorie restriction with physical activity interventions, (ii) physical activity interventions without calorie restriction and (iii) the role of physical activity on maintenance of weight loss. Through this critical examination of the literature, we have provided conclusions to address certain ambiguities regarding the role of physical activity in obesity treatment that will inform clinical practice. We have also identified several long‐standing gaps in knowledge that will inform future research.
Adaptive emotion regulation mediates the relationship between self‐compassion and depression in individuals with unipolar depression
Authors: Diedrich Alice , Burger Julian , Kirchner Mareike , Berking Matthias
Published: October 2016

Objectives

To identify the mechanisms involved in the association between self‐compassion and depression, we examined whether adaptive emotion regulation would mediate the relationship between self‐compassion and depression in individuals with unipolar depression. Furthermore, we explored which specific emotion regulation skills would be most important in this relationship.

Design and method

Sixty‐nine individuals with unipolar depression were assessed with the Self‐Compassion Scale and the Emotion Regulation Skills Questionnaire at baseline and with the Beck Depression Inventory‐II 1 week later.

Results

The results showed that successful application of emotion regulation skills mediates the association between self‐compassion and depression. Among eight specific emotion regulation skills, only the ability to tolerate negative emotions was identified as a significant mediator in the self‐compassion–depression relationship.

Conclusions

These findings provide preliminary evidence that systematically fostering self‐compassion might help depressed individuals cope with their symptoms by enhancing their abilities to tolerate undesired emotions.

Practitioner points

Systematically fostering self‐compassion through specific compassion‐focused interventions might facilitate a reduction in depressive symptoms by improving the person's emotion regulation abilities, especially by improving his or her ability to tolerate negative emotions.

Hence, compassion‐focused interventions might be particularly promising in depressed patients with a tendency to avoid negative emotions and deficits in tolerating them.
Therapeutic conversations: Therapists’ use of observational language contributes to optimal therapeutic outcomes
Authors: Banham James A. , Schweitzer Robert D.
Published: October 2016

Objective

Reflexivity is the process of critically examining one's own experience. Emerging literature suggests that reflexivity is a positive predictor of outcomes in psychotherapy. However, limited research has been conducted regarding therapists’ use of reflexivity as a therapeutic technique. In particular, we have a limited understanding of how therapists use language to initiate reflexive conversations. This study investigates the characteristics of therapist language that elicit reflexivity focused on internal and external processes.

Design and Methods

Therapeutic outcomes of 42 trainee‐therapists who provided psychotherapy to 173 clients were tracked with the OQ‐45.2 with the view of identifying client–trainee‐therapist dyads (CTTDs) with the best and poorest outcomes. Six best outcome and six poorest outcome CTTDs were identified. Thirty‐six therapy transcripts were initially coded with the Narrative Process Coding System to identify each Narrative Process Mode (NPM). Sixty external, internal, and reflexive NPMs (N = 180 NPMs) were randomly selected across all therapy transcripts for the best outcome group and the same number for the poorest outcome group. The Narrative Initiating Language Element Coding Manual, developed for this study, was used to code therapists’ use of language to initiate each NPM.

Results

Therapists belonging to the best outcome group utilized more observational language to initiate internal and reflexive NPMs. Therapists belonging to the poorest outcome group evidenced high proportions of questioning language to elicit each NPM.

Conclusions

Examining how therapists use language to elicit NPMs provides further insight as to how therapeutic language may contribute to successful therapeutic outcomes.

Practitioner points

Reflexive therapeutic conversations characterized by a greater use of observational language were associated with positive therapeutic outcomes.

Therapeutic conversations characterized by a high proportion of questioning language were associated with poorer therapeutic outcomes.

Supervisors of trainee‐therapists have a key role in coaching supervisees to use language that contributes to client treatment outcomes.
Targeted use of prednisolone with the second IVIG dose for refractory Kawasaki disease
Authors: Kimura Mitsuaki , Harazaki Masashi , Fukuoka Tetsuya , Asakura Isao , Sakai Hidemasa , Kamimaki Tsutomu , Ohkawara Ichiro , Akiyama Naoe , Tsurui Satoshi , Iwashima Satoru , Shimomura Masaki , Morishita Hideaki , Meguro Takaaki , Seto Shiro
Published: October 2016

Background

Prednisolone (PSL) has been suggested to be useful for the treatment of Kawasaki disease (KD) resistant to i.v. immunoglobulin (IVIG), but much remains to be elucidated regarding its use.

Methods

A total of 1087 subjects were involved in a two‐study multicenter prospective investigation of the effects of acute phase therapy on IVIG‐resistant KD. Subjects resistant to the first dose of IVIG were classified into high (≥10 mg/dL) and low (<10 mg/dL) serum C‐reactive protein (CRP) groups after the first dose of IVIG.

Results

In the first study, the efficacy of the second dose of IVIG in the high CRP group was significantly lower than in the low CRP group (47.8% vs 76.8%, P < 0.005). In the second study, PSL was co‐administered with the second dose of IVIG to the high CRP patients (intensified regimen). The efficacy of the intensified regimen was similar to that of the second dose of IVIG in the low CRP group (79.4% vs 83.3%). Although the difference in the incidence of persistent coronary artery lesions (CAL) between the high and low CRP groups was significant in the first study (19.6% vs 3.0%, P < 0.005), it was not significant in the second study (8.8% vs 2.4%).

Conclusions

The targeted use of PSL with the second dose of IVIG in KD patients resistant to the first dose of IVIG and who are predicted to be resistant to the second dose of IVIG, appears to be effective.
Association between genetic variability and titre of Grapevine Pinot gris virus with disease symptoms
Authors: Bertazzon N. , Forte V. , Filippin L. , Causin R. , Maixner M. , Angelini E.
Published: October 2016

The present work was carried out in order to verify the possible association between a new grapevine disease, characterized by leaf mottling and deformation, and the genetic variability and concentration of Grapevine Pinot gris virus (GPGV), a recently identified virus tentatively associated with the pathology. After vineyard surveys and the establishment of real‐time qPCR assays, characterization of GPGV isolates and evaluation of GPGV titre were assessed in more than 100 samples of grapevine Glera, collected from plants regardless of whether or not they showed the symptomatology. Results showed that there was an important association between the GPGV variants and manifestation of the symptoms, and that grapevines with symptoms harboured significantly higher GPGV titre than symptomless vines. Moreover, an interesting relationship among the phylogenetic clustering of the isolates originating from plants with symptoms and some epidemiological characteristics of the disease was found. The current study confirmed the role of GPGV in the emergent disease characterized by grapevine leaf mottling and deformation.
Prevalence and outcomes of diaphragmatic dysfunction assessed by ultrasound technology during acute exacerbation of COPD: A pilot study
Authors: Antenora Federico , Fantini Riccardo , Iattoni Andrea , Castaniere Ivana , Sdanganelli Antonia , Livrieri Francesco , Tonelli Roberto , Zona Stefano , Monelli Marco , Clini Enrico M. , Marchioni Alessandro
Published: October 2016

Background and objective

The prevalence and clinical consequences of diaphragmatic dysfunction (DD) during acute exacerbations of COPD (AECOPD) remain unknown. The aim of this study was (i) to evaluate the prevalence of DD as assessed by ultrasonography (US) and (ii) to report the impact of DD on non‐invasive mechanical ventilation (NIV) failure, length of hospital stay and mortality in severe AECOPD admitted to respiratory intensive care unit (RICU).

Methods

Forty‐one consecutive AECOPD patients with respiratory acidosis admitted over a 12‐month period to the RICU of the University Hospital of Modena were studied. Diaphragmatic ultrasound (DU) was performed on admission before starting NIV. A change in diaphragmatic thickness (ΔTdi) less than 20% during spontaneous breathing was considered to confirm the presence of dysfunction (DD+). NIV failure and other clinical outcomes (duration of mechanical ventilation MV, tracheostomy, length of hospital stay and mortality) were recorded.

Results

A total of 10 out of 41 patients (24.3%) presented DD+, which was significantly associated with steroid use (P = 0.002, R‐squared = 0.19). DD+ correlated with NIV failure (P < 0.001, R‐squared = 0.27), longer intensive care unit (ICU) stay (P = 0.02, R‐squared = 0.13), prolonged MV (P = 0.023, R‐squared = 0.15) and need for tracheostomy (P = 0.006, R‐squared = 0.20). Moreover, the Kaplan–Meyer survival estimates showed that NIV failure (log‐rank test P value = 0.001, HR = 8.09 (95% CI: 2.7–24.2)) and mortality in RICU (log‐rank test P value = 0.039, HR = 4.08 (95% CI: 1.0–16.4)) were significantly associated with DD+.

Conclusion

In hospitalized AECOPD patients submitted to NIV, severe DD was seen in almost one‐quarter of patients. DD may cause NIV failure, and impacts on the use of clinical resources and on the patient's short‐term mortality.
Choline transporter‐like1 (CHER1) is crucial for plasmodesmata maturation in Arabidopsis thaliana
Authors: Kraner Max E. , Link Katrin , Melzer Michael , Ekici Arif B. , Uebe Steffen , Tarazona Pablo , Feussner Ivo , Hofmann Jörg , Sonnewald Uwe
Published: October 2016

Plasmodesmata (PD) are microscopic pores connecting plant cells and enable cell‐to‐cell transport. Currently, little information is known about the molecular mechanisms regulating PD formation and development. To uncover components of PD development we made use of the 17 kDa movement protein (MP17) encoded by the Potato leafroll virus (PLRV). The protein is required for cell‐to‐cell movement of the virus and localises to complex PD. Forward genetic screening for Arabidopsis mutants with altered PD binding of MP17 revealed several mutant lines, while molecular genetics, biochemical and microscopic studies allowed further characterisation. Map‐based cloning of one mutant revealed a point mutation in the choline transporter‐like 1 (CHER1) protein, changing glycine247 into glutamate. Mutation in CHER1 resulted in a starch excess phenotype and stunted growth. Ultrastructure analysis of shoot apical meristems, developing and fully developed leaves showed reduced PD numbers and the absence of complex PD in fully developed leaves. This indicates that cher1 mutants are impaired in PD formation and development. Global lipid profiling revealed only slight modifications in the overall lipid composition, however, altered composition of PD‐associated lipids cannot be ruled out. Thus, cher1 is devoid of complex PD in developed leaves and provides insights into the formation of complex PD at the molecular level.
The evolution of plant microRNAs: insights from a basal eudicot sacred lotus
Authors: Shi Tao , Wang Kun , Yang Pingfang
Published: October 2016

microRNAs (miRNAs) are important noncoding small RNAs that regulate mRNAs in eukaryotes. However, under which circumstances different miRNAs/miRNA families exhibit different evolutionary trajectories in plants remains unclear. In this study, we sequenced the small RNAs and degradome from a basal eudicot, sacred lotus (Nelumbo nucifera or lotus), to identify miRNAs and their targets. Combining with public miRNAs, we predicted 57 pre‐eudicot miRNA families from different evolutionary stages. We found that miRNA families featuring older age, higher copy and target number tend to show lower propensity for miRNA family loss (PGL) and stronger signature of purifying selection during divergence of temperate and tropical lotus. Further analyses of lotus genome revealed that there is an association between loss of miRNA families in descendent plants and in duplicated genomes. Gene dosage balance is crucial in maintaining those preferentially retained MIRNA duplicates by imposing stronger purifying selection. However, these factors and selection influencing miRNA family evolution are not applicable to the putative MIRNA‐likes. Additionally, the MIRNAs participating in lotus pollen–pistil interaction, a conserved process in angiosperms, also have a strong signature of purifying selection. Functionally, sequence divergence in MIRNAs escalates expression divergence of their target genes between temperate and tropical lotus during rhizome and leaf growth. Overall, our study unravels several important factors and selection that determine the miRNA family distribution in plants and duplicated genomes, and provides evidence for functional impact of MIRNA sequence evolution.
The RNA recognition motif protein CP33A is a global ligand of chloroplast mRNAs and is essential for plastid biogenesis and plant development
Authors: Teubner Marlene , Fuß Janina , Kühn Kristina , Krause Kirsten , Schmitz‐Linneweber Christian
Published: October 2016

Chloroplast RNA metabolism depends on a multitude of nuclear‐encoded RNA‐binding proteins (RBPs). Most known chloroplast RBPs address specific RNA targets and RNA‐processing functions. However, members of the small chloroplast ribonucleoprotein family (cpRNPs) play a global role in processing and stabilizing chloroplast RNAs. Here, we show that the cpRNP CP33A localizes to a distinct sub‐chloroplastic domain and is essential for chloroplast development. The loss of CP33A yields albino seedlings that exhibit aberrant leaf development and can only survive in the presence of an external carbon source. Genome‐wide RNA association studies demonstrate that CP33A associates with all chloroplast mRNAs. For a given transcript, quantification of CP33A‐bound versus free RNAs demonstrates that CP33A associates with the majority of most mRNAs analyzed. Our results further show that CP33A is required for the accumulation of a number of tested mRNAs, and is particularly relevant for unspliced and unprocessed precursor mRNAs. Finally, CP33A fails to associate with polysomes or to strongly co‐precipitate with ribosomal RNA, suggesting that it defines a ribodomain that is separate from the chloroplast translation machinery. Collectively, these findings suggest that CP33A contributes to globally essential RNA processes in the chloroplasts of higher plants.
14‐3‐3 Proteins regulate K2P5.1 surface expression on T lymphocytes
Authors: Fernández‐Orth Juncal , Ehling Petra , Ruck Tobias , Pankratz Susann , Hofmann Majella‐Sophie , Landgraf Peter , Dieterich Daniela C. , Smalla Karl‐Heinz , Kähne Thilo , Seebohm Guiscard , Budde Thomas , Wiendl Heinz , Bittner Stefan , Meuth Sven G.
Published: October 2016

K2P5.1 channels (also called TASK‐2 or Kcnk5) have already been shown to be relevant in the pathophysiology of autoimmune disease because they are known to be upregulated on peripheral and central T lymphocytes of multiple sclerosis (MS) patients. Moreover, overexpression of K2P5.1 channels in vitro provokes enhanced T‐cell effector functions. However, the molecular mechanisms regulating intracellular K2P5.1 channel trafficking are unknown so far. Thus, the aim of the study is to elucidate the trafficking of K2P5.1 channels on T lymphocytes. Using mass spectrometry analysis, we have identified 14‐3‐3 proteins as novel binding partners of K2P5.1 channels. We show that a non‐classical 14‐3‐3 consensus motif (R‐X‐X‐pT/S‐x) at the channel's C‐terminus allows the binding between K2P5.1 and 14‐3‐3. The mutant K2P5.1/S266A diminishes the protein‐protein interaction and reduces the amplitude of membrane currents. Application of a non‐peptidic 14‐3‐3 inhibitor (BV02) significantly reduces the number of wild‐type channels in the plasma membrane, whereas the drug has no effect on the trafficking of the mutated channel. Furthermore, blocker application reduces T‐cell effector functions. Taken together, we demonstrate that 14‐3‐3 interacts with K2P5.1 and plays an important role in channel trafficking.
Metadisorder for designer light in random systems
Authors: Yu Sunkyu , Piao Xianji , Hong Jiho , Park Namkyoo
Published: October 2016

We propose the concept of metadisorder for globally collective and small-world–like waves in randomly coupled systems.
Monolignol ferulate conjugates are naturally incorporated into plant lignins
Authors: Karlen Steven D. , Zhang Chengcheng , Peck Matthew L. , Smith Rebecca A. , Padmakshan Dharshana , Helmich Kate E. , Free Heather C. A. , Lee Seonghee , Smith Bronwen G. , Lu Fachuang , Sedbrook John C. , Sibout Richard , Grabber John H. , Runge Troy M. , Mysore Kirankumar S. , Harris Philip J. , Bartley Laura E. , Ralph John
Published: October 2016

Plants have convergently evolved to use monolignol ferulate conjugates to produce lignins containing chemically labile backbone esters.
Sustained drag reduction in a turbulent flow using a low-temperature Leidenfrost surface
Authors: Saranadhi Dhananjai , Chen Dayong , Kleingartner Justin A. , Srinivasan Siddarth , Cohen Robert E. , McKinley Gareth H.
Published: October 2016

Establishing a vapor film on a low-temperature Leidenfrost surface leads to 80 to 90% drag reduction in a turbulent flow.
Determination of functional collective motions in a protein at atomic resolution using coherent neutron scattering
Authors: Hong Liang , Jain Nitin , Cheng Xiaolin , Bernal Ana , Tyagi Madhusudan , Smith Jeremy C.
Published: October 2016

Coherent neutron scattering determines the forms, time scales, and amplitudes of protein functional collective modes.
Quasi-particle interference of heavy fermions in resonant x-ray scattering
Authors: Gyenis András , da Silva Neto Eduardo H. , Sutarto Ronny , Schierle Enrico , He Feizhou , Weschke Eugen , Kavai Mariam , Baumbach Ryan E. , Thompson Joe D. , Bauer Eric D. , Fisk Zachary , Damascelli Andrea , Yazdani Ali , Aynajian Pegor
Published: October 2016

Probing the quasi-particle interference of heavy fermions by resonant x-ray scattering and scanning tunneling spectroscopy.
Microbial N Transformations and N
2
O Emission after Simulated Grassland Cultivation: Effects of the Nitrification Inhibitor 3,4-Dimethylpyrazole Phosphate (DMPP)
Authors: Duan Yun-Feng , Kong Xian-Wang , Schramm Andreas , Labouriau Rodrigo , Eriksen Jørgen , Petersen Søren O.
Published: October 2016

Grassland cultivation can mobilize large pools of N in the soil, with the potential for N leaching and N
2
O emissions. Spraying with the nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) before cultivation was simulated by use of soil columns in which the residue distribution corresponded to plowing or rotovation to study the effects of soil-residue contact on N transformations. DMPP was sprayed on aboveground parts of ryegrass and white clover plants before incorporation. During a 42-day incubation, soil mineral N dynamics, potential ammonia oxidation (PAO), denitrifying enzyme activity (DEA), nitrifier and denitrifier populations, and N
2
O emissions were investigated. The soil NO
3
−
pool was enriched with
15
N to trace sources of N
2
O. Ammonium was rapidly released from decomposing residues, and PAO was stimulated in soil near residues. DMPP effectively reduced NH
4
+
transformation irrespective of residue distribution. Ammonia-oxidizing archaea (AOA) and bacteria (AOB) were both present, but only the AOB
amoA
transcript abundance correlated with PAO. DMPP inhibited the transcription of AOB
amoA
genes. Denitrifier genes and transcripts (
nirK
,
nirS
, and clades I and II of
nosZ
) were recovered, and a correlation was found between
nirS
mRNA and DEA. DMPP showed no adverse effects on the abundance or activity of denitrifiers. The
15
N enrichment of N
2
O showed that denitrification was responsible for 80 to 90% of emissions. With support from a control experiment without NO
3
−
amendment, it was concluded that DMPP will generally reduce the potential for leaching of residue-derived N, whereas the effect of DMPP on N
2
O emissions will be significant only when soil NO
3
−
availability is limiting.

IMPORTANCE
Residue incorporation following grassland cultivation can lead to mobilization of large pools of N and potentially to significant N losses via leaching and N
2
O emissions. This study proposed a mitigation strategy of applying 3,4-dimethylpyrazole phosphate (DMPP) prior to grassland cultivation and investigated its efficacy in a laboratory incubation study. DMPP inhibited the growth and activity of ammonia-oxidizing bacteria but had no adverse effects on ammonia-oxidizing archaea and denitrifiers. DMPP can effectively reduce the potential for leaching of NO
3
−
derived from residue decomposition, while the effect on reducing N
2
O emissions will be significant only when soil NO
3
−
availability is limiting. Our findings provide insight into how DMPP affects soil nitrifier and denitrifier populations and have direct implications for improving N use efficiency and reducing environmental impacts during grassland cultivation.
Identification and Characterization of a Large Protein Essential for Degradation of the Crystalline Region of Cellulose by Cytophaga hutchinsonii
Authors: Wang Sen , Zhao Dong , Bai Xinfeng , Zhang Weican , Lu Xuemei
Published: October 2016

Cytophaga hutchinsonii
is a Gram-negative bacterium that can efficiently degrade crystalline cellulose by a unique mechanism different from the free cellulase or cellulosome strategy. In this study,
chu_3220
, encoding the hypothetical protein CHU_3220 (205 kDa), was identified by insertional mutation and gene deletion as the first gene essential for degradation of the crystalline region but not the amorphous region of cellulose by
C. hutchinsonii
. A
chu_3220
deletion mutant was defective in the degradation of crystalline cellulose and increased the degree of crystallinity of Avicel PH101 but could still degrade amorphous cellulose completely. CHU_3220 was found to be located on the outer surface of the outer membrane and could bind to cellulose. It contains 15 PbH1 domains and a C-terminal domain (CHU_C) that was proved to be critical for the localization of CHU_3220 on the cell surface and the function of CHU_3220 in crystalline cellulose degradation. Moreover, the degradation of crystalline cellulose was intact-cell dependent and inhibited by NaN
3
. Further study showed that
chu_3220
was induced by cellulose and that the endoglucanase activity on the cell surface was significantly reduced without
chu_3220
. Real-time PCR revealed that the transcription of most genes encoding endoglucanases located on the cell surface was decreased in the
chu_3220
deletion mutant, indicating that
chu_3220
might also play a role in the regulation of the expression of some endoglucanases.

IMPORTANCE
Cytophaga hutchinsonii
could efficiently degrade crystalline cellulose with a unique mechanism without cellulosomes and free cellulases. It lacks proteins that are thought to play important roles in disruption of the crystalline region of cellulose, including exoglucanases, lytic polysaccharide monooxygenases, expansins, expansin-like proteins, or swollenins, and most of its endoglucanases lack carbohydrate binding modules. The mechanism of the degradation of crystalline cellulose is still unknown. In this study,
chu_3220
was identified as the first gene essential for the degradation of the crystalline region but not the amorphous region of cellulose. CHU_3220 is a high-molecular-weight protein located on the outer surface of the outer membrane and could bind to cellulose. We proposed that CHU_3220 might be an essential component of a protein complex on the cell surface in charge of the decrystallization of crystalline cellulose. The degradation of crystalline cellulose by
C. hutchinsonii
was not only dependent on intact cells but also required the energy supplied by the cells. This was obviously different from other known cellulose depolymerization system. Our study has shed more light on the novel strategy of crystalline cellulose degradation by
C. hutchinsonii
.
Disentangling the Taxonomy of Rickettsiales and Description of Two Novel Symbionts (“Candidatus Bealeia paramacronuclearis” and “Candidatus Fokinia cryptica”) Sharing the Cytoplasm of the Ciliate Protist Paramecium biaurelia
Authors: Szokoli Franziska , Castelli Michele , Sabaneyeva Elena , Schrallhammer Martina , Krenek Sascha , Doak Thomas G. , Berendonk Thomas U. , Petroni Giulio
Published: October 2016

In the past 10 years, the number of endosymbionts described within the bacterial order
Rickettsiales
has constantly grown. Since 2006, 18 novel
Rickettsiales
genera inhabiting protists, such as ciliates and amoebae, have been described. In this work, we characterize two novel bacterial endosymbionts from
Paramecium
collected near Bloomington, IN. Both endosymbiotic species inhabit the cytoplasm of the same host. The Gram-negative bacterium “
Candidatus
Bealeia paramacronuclearis” occurs in clumps and is frequently associated with the host macronucleus. With its electron-dense cytoplasm and a distinct halo surrounding the cell, it is easily distinguishable from the second smaller symbiont, “
Candidatus
Fokinia cryptica,” whose cytoplasm is electron lucid, lacks a halo, and is always surrounded by a symbiontophorous vacuole. For molecular characterization, the small-subunit rRNA genes were sequenced and used for taxonomic assignment as well as the design of species-specific oligonucleotide probes. Phylogenetic analyses revealed that “
Candidatus
Bealeia paramacronuclearis” clusters with the so-called “basal”
Rickettsiales
, and “
Candidatus
Fokinia cryptica” belongs to “
Candidatus
Midichloriaceae.” We obtained tree topologies showing a separation of
Rickettsiales
into at least two groups: one represented by the families
Rickettsiaceae
,
Anaplasmataceae
, and “
Candidatus
Midichloriaceae” (RAM clade), and the other represented by “basal
Rickettsiales
,” including “
Candidatus
Bealeia paramacronuclearis.” Therefore, and in accordance with recent publications, we propose to limit the order
Rickettsiales
to the RAM clade and to raise “basal
Rickettsiales
” to an independent order,
Holosporales
ord. nov., inside
Alphaproteobacteria
, which presently includes four family-level clades. Additionally, we define the family “
Candidatus
Hepatincolaceae” and redefine the family
Holosporaceae
.

IMPORTANCE
In this paper, we provide the characterization of two novel bacterial symbionts inhabiting the same
Paramecium
host (Ciliophora, Alveolata). Both symbionts belong to “traditional”
Rickettsiales
, one representing a new species of the genus “
Candidatus
Fokinia” (“
Candidatus
Midichloriaceae”), and the other representing a new genus of a “basal”
Rickettsiales
. According to newly characterized sequences and to a critical revision of recent literature, we propose a taxonomic reorganization of “traditional”
Rickettsiales
that we split into two orders:
Rickettsiales sensu stricto
and
Holosporales
ord. nov. This work represents a critical revision, including new records of a group of symbionts frequently occurring in protists and whose biodiversity is still largely underestimated.
Effect of a national urgent care telephone triage service on population perceptions of urgent care provision: controlled before and after study
Authors: Knowles E , O'Cathain A , Turner J , Nicholl J
Published: October 2016

Objective

To measure the effect of an urgent care telephone service NHS 111 on population perceptions of urgent care.

Design

Controlled before and after population survey, using quota sampling to identify 2000 respondents reflective of the age/sex profile of the general population.

Setting

England. 4 areas where NHS 111 was introduced, and 3 control areas where NHS 111 had yet to be introduced.

Participants

28 071 members of the general population, including 2237 recent users of urgent care.

Intervention

NHS 111 offers advice to members of the general population seeking urgent care, recommending the best service to use or self-management. Policymakers introduced NHS 111 to improve access to urgent care.

Outcomes measures

The primary outcome was change in satisfaction with recent urgent care use 9 months after the launch of NHS 111. Secondary outcomes were change in satisfaction with urgent care generally and with the national health service.

Results

The overall response rate was 28% (28 071/100 408). 8% (2237/28 071) had used urgent care in the previous 3 months. Of the 652 recent users of urgent care in the NHS 111 intervention areas, 9% (60/652) reported calling NHS 111 in the ‘after’ period. There was no evidence that the introduction of NHS 111 was associated with a changed perception of recent urgent care. For example, the percentage rating their experience as excellent remained at 43% (OR 0.97, 95% CI 0.69 to 1.37). Similarly, there was no change in population perceptions of urgent care generally (1.06, 95% CI 0.95 to 1.17) or the NHS (0.94, 95% CI 0.85 to 1.05) following the introduction of NHS 111.

Conclusions

A new telephone triage service did not improve perceptions of urgent care or the health service. This could be explained by the small amount of NHS 111 activity in a large emergency and urgent care system.
State of the art of chronic spontaneous urticaria in Italy: a multicentre survey to evaluate physicians’ and patients’ perspectives
Authors: Rimoldi Marco , Rossi Oliviero , Rota Nadia
Published: October 2016

Objective

To assess the clinical status of chronic spontaneous urticaria (CSU) and understand treatment approaches in Italy through specialists who treat CSU (dermatologists and allergy specialists) and CSU patients' experience.

Design

Multicentre survey.

Setting

Online structured questionnaires (one for physicians and one for patients).

Participants

Physicians and patients with CSU in Italy.

Interventions

None.

Primary/secondary outcomes

Physician and patient attitudes/experiences.

Results

Survey results from 160 allergy and 160 dermatology specialists show that specialists see a median of 40 (IQR 20–80) patients with CSU/year. While most specialists (56%) know the CSU guidelines, only 27% use them regularly (36% of allergy specialists vs 18% of dermatologists). This is reflected in treatment choices with differences between physicians who use guidelines regularly and those who do not: 91.6% vs 71.7% choose standard-dose, non-sedating antihistamines as first-line treatment; 85.9% vs 56.0% select up-dosing for second-line treatment and 65.3% vs 37.2% add leukotriene receptor antagonists or H2-antihistamines as third-line treatment. The diaries from 1385 patients highlight that, regardless of treatment regimen, 29.4% of currently treated patients are refractory to therapy. Specialists aim to resolve symptoms and only 7.8% report improving quality of life (QoL) as a priority. Only 16.6% of specialists are familiar with and use the Urticaria Activity Score while 46.9% do not know it. Overall, 537 patients with CSU were surveyed (median age 37 years, IQR 30–46; 44.3% men; median disease duration 5 years, IQR 3–20). Approximately 62% confirm that CSU negatively impacts their QoL. Patients also complain of difficulties in getting information and support: <5% of medical centres provide patient support services.

Conclusions

In Italy, the gap between guideline-based care and QoL-related needs in CSU patients affects treatment satisfaction. This information could be used to improve the management of CSU in Italy.
Are prenatal mercury levels associated with subsequent blood pressure in childhood and adolescence? The Avon prebirth cohort study
Authors: Gregory Steve , Iles-Caven Yasmin , Hibbeln Joseph R , Taylor Caroline M , Golding Jean
Published: October 2016

Objectives

There have been conflicting data suggesting that prenatal mercury exposure is associated with adverse cardiovascular measures in children. We therefore analysed a large prospective population study to investigate whether prenatal mercury exposure might influence offspring blood pressure (BP) and heart rate adversely.

Design

Prospective birth cohort.

Setting

The Avon Longitudinal Study of Parents and Children (ALSPAC).

Participants

Maternal whole blood collected in the first half of pregnancy was assayed for mercury and selenium. The offspring were followed throughout childhood and adolescence.

Outcome measures

Offspring resting BP and heart rates measured under standard conditions on six occasions between ages 7 and 17 years (numbers analysed: 1754 at 7 years to 1102 at 17).

Results

Statistical analyses took account of various factors present in pregnancy, including family adversity, maternal age, parity, smoking and alcohol intake. Unadjusted and adjusted regression analyses assessed the relationship between maternal prenatal mercury levels and offspring resting systolic and diastolic BP, and heart rates. A final set of analyses took account of selenium. Each analysis was carried out for all offspring, those whose mothers had, and those that had not, consumed fish during pregnancy. Further analysis for all offspring ascertained whether there were significant interaction effects between the sexes. There was little evidence to suggest that prenatal mercury exposure resulted in a clinically important increase in offspring BP in the whole group, since no effect size for an increase of 1 SD of blood mercury level was >0.3 mm Hg. Only 1 association was significant at p<0.05 and therefore likely due to chance.

Conclusions

This study reveals no evidence to support the hypothesis that prenatal mercury exposure has adverse long-term effects on offspring BP or heart rates during childhood or adolescence.
Does a modified STarT Back Tool predict outcome with a broader group of musculoskeletal patients than back pain? A secondary analysis of cohort data
Authors: Hill J C , Afolabi E K , Lewis M , Dunn K M , Roddy E , van der Windt D A , Foster N E
Published: October 2016

Objectives

The STarT Back Tool has good predictive performance for non-specific low back pain in primary care. We therefore aimed to investigate whether a modified STarT Back Tool predicted outcome with a broader group of musculoskeletal patients, and assessed the consequences of using existing risk-group cut-points across different pain regions.

Setting

Secondary analysis of prospective data from 2 cohorts: (1) outpatient musculoskeletal physiotherapy services (PhysioDirect trial n=1887) and (2) musculoskeletal primary–secondary care interface services (SAMBA study n=1082).

Participants

Patients with back, neck, upper limb, lower limb or multisite pain with a completed modified STarT Back Tool (baseline) and 6-month physical health outcome (Short Form 36 (SF-36)).

Outcomes

Area under the receiving operator curve (AUCs) tested discriminative abilities of the tool's baseline score for identifying poor 6-month outcome (SF-36 lower tertile Physical Component Score). Risk-group cut-points were tested using sensitivity and specificity for identifying poor outcome using (1) Youden's J statistic and (2) a clinically determined rule that specificity should not fall below 0.7 (false-positive rate <30%).

Results

In PhysioDirect and SAMBA, poor 6-month physical health was 18.5% and 28.2%, respectively. Modified STarT Back Tool score AUCs for predicting outcome in back pain were 0.72 and 0.79, neck 0.82 and 0.88, upper limb 0.79 and 0.86, lower limb 0.77 and 0.83, and multisite pain 0.83 and 0.82 in PhysioDirect and SAMBA, respectively. Differences between pain region AUCs were non-significant. Optimal cut-points to discriminate low-risk and medium-risk/high-risk groups depended on pain region and clinical services.

Conclusions

A modified STarT Back Tool similarly predicts 6-month physical health outcome across 5 musculoskeletal pain regions. However, the use of consistent risk-group cut-points was not possible and resulted in poor sensitivity (too many with long-term disability being missed) or specificity (too many with good outcome inaccurately classified as ‘at risk’) for some pain regions. The draft tool is now being refined and validated within a new programme of research for a broader musculoskeletal population.

Trial registration number

ISRCTN55666618; Post results.
Mental health associations with eczema, asthma and hay fever in children: a cross-sectional survey
Authors: Hammer-Helmich Lene , Linneberg Allan , Obel Carsten , Thomsen Simon Francis , Tang Møllehave Line , Glümer Charlotte
Published: October 2016

Objective

This study aimed to examine the association of eczema, asthma and hay fever with mental health in a general child population and to assess the influence of parental socioeconomic position on these associations.

Methods

We conducted a cross-sectional health survey of children aged 3, 6, 11 and 15 years in the City of Copenhagen, Denmark. Individual questionnaire data on eczema, asthma, and hay fever and mental health problems assessed using the Strengths and Difficulties Questionnaire (SDQ) was linked to register data on demographics and parental socioeconomic position. 9215 (47.9%) children were included in the analyses.

Results

Linear regression analyses showed that children with current eczema symptoms had higher SDQ scores (mean difference, 95% CI) of emotional problems (0.26, 0.12 to 0.39), conduct problems (0.19, 0.09 to 0.29) and hyperactivity problems (0.32, 0.16 to 0.48); children with current asthma symptoms had higher SDQ scores of emotional problems (0.45, 0.32 to 0.58), conduct problems (0.28, 0.18 to 0.38) and hyperactivity problems (0.52, 0.35 to 0.69); and children with current hay fever symptoms had higher SDQ scores of emotional problems (0.57, 0.42 to 0.72), conduct problems (0.22, 0.11 to 0.33), hyperactivity problems (0.44, 0.26 to 0.61) and peer problems (0.14, 0.01 to 0.26), compared with children without current symptoms of the relevant disease. For most associations, parental socioeconomic position did not modify the effect.

Conclusions

Children with eczema, asthma or hay fever had more emotional, conduct and hyperactivity problems, but not peer problems, compared with children without these diseases. Atopic diseases added equally to the burden of mental health problems independent of socioeconomic position.