bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific N‐terminal cleavage of ribosomal protein L27 in Staphylococcus aureus and related bacteria
Authors: Wall Erin A. , Caufield J. Harry , Lyons Charles E. , Manning Keith A. , Dokland Terje , Christie Gail E.
Published: November 2014

Ribosomal protein L27 is a component of the eubacterial large ribosomal subunit that has been shown to play a critical role in substrate stabilization during protein synthesis. This function is mediated by the L27 N‐terminus, which protrudes into the peptidyl transferase center. In this report, we demonstrate that L27 in Staphylococcus aureus and other Firmicutes is encoded with an N‐terminal extension that is not present in most Gram‐negative organisms and is absent from mature ribosomes. We have identified a cysteine protease, conserved among bacteria containing the L27 N‐terminal extension, which performs post‐translational cleavage of L27. Ribosomal biology in eubacteria has largely been studied in the Gram‐negative bacterium Escherichia coli; our findings indicate that there are aspects of the basic biology of the ribosome in S. aureus and other related bacteria that differ substantially from that of the E. coli ribosome. This research lays the foundation for the development of new therapeutic approaches that target this novel pathway.
VIII. CONCLUSIONS AND FUTURE DIRECTIONS OF THE RESEARCH ON PHYSICAL ACTIVITY AND CHILDHOOD COGNITIVE AND BRAIN HEALTH
Authors: Hillman Charles H.
Published: November 2014

This chapter serves as a summary to the monograph. The main purpose is to concisely merge the individual chapters into a cohesive summary around markers of health behaviors and their relation to childhood cognition and brain health. In addition, future directions for research in this area are briefly discussed with the goal of shaping future research in several directions. Issues surrounding the need for causality and ethical considerations are also described. Finally, this chapter places the link between health behaviors and cognition within the greater context of the educational environment, lifelong health, and effective function.
The c‐di‐GMP phosphodiesterase BifA is involved in the virulence of bacteria from the Pseudomonas syringae complex
Authors: Aragón Isabel M. , Pérez‐Mendoza Daniel , Gallegos María‐Trinidad , Ramos Cayo
Published: November 2014

In a recent screen for novel virulence factors involved in the interaction between Pseudomonas savastanoi pv. savastanoi and the olive tree, a mutant was selected that contained a transposon insertion in a putative cyclic diguanylate (c‐di‐GMP) phosphodiesterase‐encoding gene. This gene displayed high similarity to bifA of Pseudomonas aeruginosa and Pseudomonas putida. Here, we examined the role of BifA in free‐living and virulence‐related phenotypes of two bacterial plant pathogens in the Pseudomonas syringae complex, the tumour‐inducing pathogen of woody hosts, P. savastanoi pv. savastanoi NCPPB 3335, and the pathogen of tomato and Arabidopsis, P. syringae pv. tomato DC3000. We showed that deletion of the bifA gene resulted in decreased swimming motility of both bacteria and inhibited swarming motility of DC3000. In contrast, overexpression of BifA in P. savastanoi pv. savastanoi had a positive impact on swimming motility and negatively affected biofilm formation. Deletion of bifA in NCPPB 3335 and DC3000 resulted in reduced fitness and virulence of the microbes in olive (NCPPB 3335) and tomato (DC3000) plants. In addition, real‐time monitoring of olive plants infected with green fluorescent protein (GFP)‐tagged P. savastanoi cells displayed an altered spatial distribution of mutant ΔbifA cells inside olive knots compared with the wild‐type strain. All free‐living phenotypes that were altered in both ΔbifA mutants, as well as the virulence of the NCPPB 3335 ΔbifA mutant in olive plants, were fully rescued by complementation with P. aeruginosa BifA, whose phosphodiesterase activity has been demonstrated. Thus, these results suggest that P. syringae and P. savastanoi BifA are also active phosphodiesterases. This first demonstration of the involvement of a putative phosphodiesterase in the virulence of the P. syringae complex provides confirmation of the role of c‐di‐GMP signalling in the virulence of this group of plant pathogens.
Double‐blinded, randomized controlled trial of N‐acetylcysteine for prevention of acute kidney injury in high risk patients undergoing off‐pump coronary artery bypass
Authors: Song Jong Wook , Shim Jae Kwang , Soh Sarah , Jang Jaewon , Kwak Young Lan
Published: November 2014

Aim

The aim of this study was to investigate the influence of perioperative N‐acetylcysteine (NAC) administration, a known antioxidant, on the incidence of acute kidney injury (AKI) after off‐pump coronary bypass surgery (OPCAB) in patients with known risk factors of AKI.

Methods

One hundred and seventeen patients with ≥1 of the following risk factors of AKI were randomized into either the control (n = 57) or the NAC (n = 60) group; (i) preoperative serum creatinine >1.4 mg/dL; (ii) left ventricular ejection fraction <35% or congestive heart failure (iii) age >70 years (iv) diabetes or (v) re‐operation. Patients in the NAC group received 150 mg/kg of NAC IV bolus at anaesthetic induction followed by a continuous infusion at 150 mg/kg per day for 24 h. AKI was diagnosed based on Acute Kidney Injury Network criteria during 48 h postoperatively.

Results

The incidence of AKI was 32% (19/60) and 35% (20/57) in the control and the NAC group, respectively (P = 0.695). The serum concentrations of creatinine and cystatin C were similar between the groups throughout the study period. Fluid balance including the amount of blood loss and transfusion requirement were similar between the groups except the amount of postoperative urine output, which was higher in the control group compared with the NAC group (5528 ± 1247 mL vs. 4982 ± 1185 mL, control vs. NAC, P = 0.017).

Conclusion

Perioperative administration of NAC did not prevent the development of postoperative AKI after OPCAB in highly susceptible patients to AKI.
Begonia baik and B. padawanensis spp. nov. (Begoniaceae) from sandstone areas in Sarawak, Malaysia
Authors: Lin Che‐Wei , Chung Shih‐Wen , Peng Ching‐I
Published: November 2014

Two new species of Begonia (Begoniaceae), B. baik and B. padawanensis, from Sarawak are described and illustrated. Begonia baik, a member of sect. Petermannia, resembles B. conipila, but is distinguishable by having glabrous ovary (vs sparsely hispid) and margins of bracts dentate and glandular hairy (vs entire). Begonia padawanensis (sect. Reichenheimia) is similar to B. andersonii, differing in the leaves being obtriangular‐spatulate (vs orbicular) and having 5 pistillate flower tepals (vs 4). Both new species were discovered in a sandstone area in Padawan, Sarawak.
Epiphytic lichens onJuniperus communis– an unexplored component of biodiversity in threatened alvar grassland
Authors: Jüriado Inga , Leppik Ede , Lõhmus Piret , Randlane Tiina , Liira Jaan
Published: November 2014

Semi‐natural grasslands, among them thin‐soil calcareous grasslands (alvars), have great conservation value but have become increasingly rare in Europe. The main threat to alvar grasslands is the encroachment by juniperJuniperus communisand therefore it is usually removed during the restoration practice. Juniper can also be a host plant for many epiphytic lichens, but its role as a phorophyte is poorly known. We studied epiphytic lichen diversity on 126 junipers in 17 sites in western Estonia and found 140 lichenized taxa including several rare and red‐listed species. Using indirect and direct multivariate analyses (DCA, pCCA) and general linear models we revealed that both habitat and phorophyte properties affect lichen assemblies on juniper. Lichen species richness per site showed a unimodal relationship with compound factors of site productivity and juniper characteristics (stem circumference and juniper width). Lichen species richness per phorophyte was increasing with its size and with the proportion of dead branches, and was twice higher in plate alvars than in ryhk alvars. Also, the species composition in plate alvars differed from ryhk alvars by having 42 characteristic lichen species in plate alvars vs three indicators of ryhk alvars. The composition of lichens was significantly influenced by encroachment of alvars, e.g. by high juniper cover and shrub layer height, as well as by the proportion of dead branches and stem circumference of juniper. We conclude that the epiphytic lichen assemblies on junipers are threatened by grassland encroachment similarly to ground layer lichen assemblies. We suggest that some old and scencent junipers should be preserved during the restoration of alvar grasslands.
Aspidistra laotica, A. multiflora, A. oviflora and A. semiaperta spp. nov. (Asparagaceae, Convallariaceae s.s.) from eastern Indochina
Authors: Averyanov Leonid V. , Tillich H.‐J.
Published: November 2014

Aspidistra laotica, A. multiflora, A. oviflora and A. semiaperta discovered recently are described and illustrated as species new to science. All novelties are local endemics of northern Vietnam and central Laos.
TAL effectors – pathogen strategies and plant resistance engineering
Authors: Boch Jens , Bonas Ulla , Lahaye Thomas
Published: November 2014

Transcription activator‐like effectors (TALEs) from plant pathogenic Xanthomonas spp. and the related RipTALs from Ralstonia solanacearum are DNA‐binding proteins with a modular DNA‐binding domain. This domain is both predictable and programmable, which simplifies elucidation of TALE function in planta and facilitates generation of DNA‐binding modules with desired specificity for biotechnological approaches. Recently identified TALE host target genes that either promote or stop bacterial disease provide new insights into how expression of TALE genes affects the plant–pathogen interaction. Since its elucidation the TALE code has been continuously refined and now provides a mature tool that, in combination with transcriptome profiling, allows rapid isolation of novel TALE target genes. The TALE code is also the basis for synthetic promoter‐traps that mediate recognition of TALE or RipTAL proteins in engineered plants. In this review, we will summarize recent findings in plant‐focused TALE research. In addition, we will provide an outline of the newly established gene isolation approach for TALE or RipTAL host target genes with an emphasis on potential pitfalls.
Translational regulation during stage transitions in malaria parasites
Authors: Cui Liwang , Lindner Scott , Miao Jun
Published: November 2014

The complicated life cycle of the malaria parasite involves a vertebrate host and a mosquito vector, and translational regulation plays a prominent role in orchestrating the developmental events in the two transition stages: gametocytes and sporozoites. Translational regulation is executed in both global and transcript‐specific manners. Plasmodium uses a conserved mechanism involving phosphorylation of eIF2α to repress global protein synthesis during the latent period of sporozoite development in the mosquito salivary glands. Transcript‐specific translational regulation is achieved by a network of RNA‐binding proteins (RBPs), among which the Dhh1 RNA helicase DOZI and Puf family RBPs are by far the best studied in Plasmodium. While the DOZI complex defines a new P granule with a role in protecting certain gametocyte mRNAs from degradation, the Puf proteins appear to repress expression of mRNAs in both gametocytes and sporozoites. These examples underscore the significance of translational regulation in Plasmodium development.
Active dispersal is differentially affected by inter‐ and intraspecific competition in closely related nematode species
Authors: De Meester Nele , Derycke Sofie , Rigaux Annelien , Moens Tom
Published: November 2014

Competition is one of the main drivers of dispersal, which can be an important mechanism to achieve permanent or temporal coexistence of multiple species. This coexistence can be achieved by a dispersal‐competition tradeoff, spatial store effects or neutral dynamics. Here we test the effect of inter‐ and intraspecific competition on dispersal of four species of the marine nematode species complexLitoditis marina. A previous study in closed microcosms without a possibility for dispersal had demonstrated pronounced interspecific competition, leading to the exclusion of one species. We now investigated whether 1) the dispersal is affected by interspecific interactions, by intraspecific competition (density) or by food availability, 2) the dispersal dynamics influence assemblage composition and can lead to co‐occurrence of the species, and 3) the abiotic environment (here salinity) can affect these dynamics. We show that density is the main driver for dispersal in two of the four species. Dispersal of a third species always started at the same time irrespective of density, whereas in the fourth species interspecific interactions accelerated dispersal. Remarkably, this fourth species was not a strong competitor, suggesting that a dispersal–competition tradeoff does not explain the observed coexistence. Salinity did not alter the timing of dispersal when interspecific interactions were present but did affect assemblage composition. Consequently, spatial store effects may influence coexistence. All four species co‐occurred in fairly stable abundances throughout the present experiment indicating the importance of species specific dispersal strategies for coexistence. Co‐occurrence can be facilitated because competition is postponed or avoided by dispersal. Neutral dynamics also played a role as intra‐ and interspecific competition were of similar importance in three of the four species. We conclude that dispersal is a driver of the coexistence of closely related nematode species, and that population density and interspecific interactions shape these dynamics.
Prior Authorization in the Treatment of Patients with pDPN and FM
Authors: Placzek Hilary E. D. , Masters Elizabeth T. , Gu Tao , Cappelleri Joseph C. , Wasser Thomas E. , Clair Andrew G. , Cook Joseph P. , Eisenberg Debra F.
Published: November 2014

Purpose

To determine prior authorization (PA) impact on healthcare utilization, costs, and pharmacologic treatment patterns for painful diabetic peripheral neuropathy (pDPN) and fibromyalgia (FM).

Methods

This retrospective, observational, longitudinal cohort study used medical and pharmacy claims data. Newly diagnosed patients treated for FM or pDPN between 7/1/2007 and 12/31/2011 were included. PA and no PA groups were matched by propensity score 4:1. Medical resource utilization, direct medical and pharmacy costs, and treatment pattern differences were compared. Pre and postindex differences between PA and no PA cohorts were determined by difference in difference analysis.

Results

Analysis of 2,315 FM patients (1,852 PA; 463 no PA) demonstrated greater increases in postindex all‐cause costs ($197; P = 0.6673) and disease‐related costs ($72; P = 0.4186) in the PA cohort. Analysis of 1,300 pDPN patients (1,040 PA; 260 no PA) demonstrated postindex all‐cause cost increases of $1,155 more in the no PA cohort (P = 0.6248); disease‐related costs decreased $2,809 more in the no PA cohort (P = 0.4312). Treatment patterns were similar between cohorts; opioid usage was higher in the FM PA cohort (P = 0.0082).

Conclusions

There was no evidence of statistically significant differences between PA and no PA cohorts in either FM or pDPN populations for total all‐cause or disease‐related costs.
Prevalence of insomnia and its clinical correlates in a general population in Turkey
Authors: Benbir Gulcin , Demir Ahmet Ugur , Aksu Murat , Ardic Sadik , Firat Hikmet , Itil Oya , Ozgen Fuat , Yılmaz Hikmet , Karadeniz Derya
Published: November 2014

Aim

The prevalence of insomnia is influenced by environmental factors. This study aimed to investigate the prevalence of insomnia and its sociodemographic and clinical correlates in a general population‐based survey in Turkey.

Methods

This population‐based study included 4758 subjects among 5021 who participated in the Turkish Adult Population Epidemiology of Sleep Disorders study. Questionnaire items evaluating insomnia were adapted from the International Classification of Sleep Disorders II and the DSM‐IV‐TR. Subjects with restless legs syndrome were excluded.

Results

Insomnia was found to be associated with older age (18–24 years, 9.8%; 25–44 years, 11.7%; 45–64 years, 13.8%; 65 years or older, 13.9%), lower income level (<500 USD, 16.5%), time spent watching TV (6–8 h or more, 18.4%), tea consumption in the evening (≥6 glasses, 14.5%) and smoking status (current and ex‐smoker, both 14.2%) in multiple logistic regression analysis. In respect to other medical disorders, insomnia was significantly associated with the presence of hypertension, diabetes and heart diseases after the adjustment for relevant risk factors for each disease, across all age and sex groups.

Conclusions

Insomnia is a major health problem in our population, affecting subjects in the working age group and those of lower socioeconomic status. It should especially be screened in patients with chronic diseases. A relatively low proportion of insomnia diagnosed as a sleep disorder suggests that this condition and its clinical correlates are possibly under‐recognized.
High psychiatric comorbidity in adolescents with dissociative disorders
Authors: Bozkurt Hasan , Duzman Mutluer Tuba , Kose Cigdem , Zoroglu Salih
Published: November 2014

Aim

The aim of this study was to evaluate psychiatric comorbidity rates and patterns in a sample of clinically referred adolescents diagnosed with dissociative disorders (DD) by using a structured interview.

Methods

All participants completed a comprehensive test battery, which consisted of a questionnaire for sociodemographic data and clinical history, Child Posttraumatic Stress Reaction Index, Childhood Abuse and Neglect Questionnaire and the Adolescent Dissociative Experiences Scale. Diagnosis was made by the Structured Clinical Interview for DSM‐IV Dissociative Disorders. Psychiatric comorbidity was assessed using the Schedule for Affective Disorders and Schizophrenia for School Age Children – Present and Lifetime Version.

Results

A total of 25 adolescent subjects aged 12–18 years participated in the study. Ten adolescents were diagnosed as having dissociative identity disorder and 15 of them were diagnosed as having dissociative disorder–not otherwise specified based on the Structured Clinical Interview for DSM‐IV Dissociative Disorders findings. Adolescents with dissociative identity disorder were found to have higher scores on the Adolescent Dissociative Experiences Scale and Child Posttraumatic Stress Reaction Index than the dissociative disorder–not otherwise specified group. Sexual and physical abuses were also found to be among the main traumatic events. Incest was reported in six cases of the study sample. All subjects had at least one comorbid psychiatric disorder. The most common psychiatric diagnoses were major depressive disorder (n = 25; 100%) and post‐traumatic stress disorder (n = 22; 88%).

Conclusion

High psychiatric comorbidity rates were found in adolescents diagnosed with DD. A prevalent history of abuse and traumatic events was represented. Clinicians should be aware of the impacts of DD on adolescents' mental health.
Judicial enforcement deputies: Causes and effects ofChinese judges enforcing environmental administrative decisions
Authors: Zhang Xuehua
Published: November 2014

This paper explores how and whyChinese courts became involved in regulating pollution by aiding administrative agencies in executing sanction decisions and collecting pollution levies. It also studies the effects of their regulatory involvement, both in terms of deterrence inferred from available information, as well as the compliance behavior of regulated actors defined as payment of regulatory penalties. It finds that judicial involvement in regulatory enforcement proved to be short‐lived and depended on a particular context at a particular period of time when a regulatory need coincided with administrative and financial judicial needs and particular judges. The paper also finds that court involvement enhanced deterrence in terms of certainty of punishment and to some extent the severity of punishment; however that deterrent effect was undermined by the close relationship between the courts and the regulated entities as fines and levies were almost always negotiated. In effect, deterrence increased the number of compliers paying levies without increasing the depth of compliance in terms of their full payment.
Learning to “Deal” and “De‐escalate”: How Men in Nursing Manage Self and Patient Emotions
Authors: Cottingham Marci D.
Published: November 2014

While prior research has explored how gender frames emotion management processes, little work has specifically examined the links between men's emotion management in a caring profession and theory on masculine emotionality. Stereotyped as less sensitive to their own and others' emotions, male nurses confront unique challenges in navigating the profession's emotional demands. Drawing on men's diaries and interviews, I examine emergent emotion‐based processes that characterize men's emotional labor—the strategies men use to manage their own and patient emotions on the job. In managing their own emotion, men's narratives reveal three distinct strategies: reframing the nurse role, distancing, and relinquishing situational control. In managing patient emotions, they frame control over their own emotions as a means for managing others and emphasize knowledge/education as a strategy for managing patient stress and anxiety. While both male and female nurses may engage these strategies, men's emotion management implicates the simultaneous reproduction and disruption of hegemonic masculinity and the reason/emotion dualisms that undergird the current gender system. Implications for masculinity and emotion management theory, as well as recruiting, training, and retaining male nurses are explored.
Irish Existentials in Context
Authors: McCloskey James
Published: November 2014

This paper aims to contribute to the comparative typology of existential constructions by examining Irish existentials in detail. It goes on to engage some of the central theoretical issues raised in that investigation and provides support for the bifurcated analysis of the definiteness restriction proposed by McNally (1992). It identifies what is argued to be a true existential predicate and argues that there is no common syntactic form for existentials crosslinguistically; rather, the observed commonalities among existentials across languages reflect semantic primitives out of which they are constructed. Diversity in the expression of existential propositions principally reflects different patterns of lexicalization.
Th/Ex, Agreement, and Case in Expletive Sentences
Authors: Sobin Nicholas
Published: November 2014

Recent accounts of existential sentences (ES) within the government‐and‐binding/Minimalist Program tradition (Chomsky 2000, 2001; Deal 2009) claim that nominative Case valuation and ϕ‐agreement take place inES(directly or indirectly) between T and the associateDP, essentially the same as between T and “subject” in non‐ES. However, the surface facts of Case and ϕ‐agreement inESrun contrary to such claims (e.g.,There is only me in that picture/*There am only I in that picture;There is/?*are a boy and a girl at the door). Furthermore, such accounts leave unexplained the short‐movement phenomenon (including Milsark's [1974] “LeftmostbeCondition”) found inES(e.g.,There is someone being arrested/* There is being someone arrestedorThere is a train arriving/*There is arriving a train). Following claims of Richards & Biberauer (2005) and Deal (2009) that merger ofthereinESis low, I explore the possibility that “short movement” inES, as well as the ban on multiple instances ofthere, is accounted for via Extended Projection Principle features of the relevant verbalizing functional heads that are articulated into their Agree and Merge components. Furthermore, an analysis of Case and ϕ‐agreement is presented that accounts directly for the broad range of ϕ‐agreement forms (including “frozen” forms and first‐conjunct agreement), the necessarily accusative Case form of pronominal associates allowableES, and the ban on ϕ‐agreement with pronominal associates inES.
Atg23 and Atg27 Act at the Early Stages of Atg9 Trafficking in S. cerevisiae
Authors: Backues Steven K. , Orban Daniel P. , Bernard Amélie , Singh Kushal , Cao Yang , Klionsky Daniel J.
Published: November 2014

Atg9 is a conserved multipass transmembrane protein with an essential role in autophagy. In Saccharomyces cerevisiae, it travels through the secretory pathway to a unique compartment, the Atg9 peripheral structures. These structures are then targeted to the phagophore assembly site (PAS), where they are proposed to help deliver membrane to the forming autophagosome. We used ‘in vivo reconstitution’ of this process in a multiple‐knockout strain to define four proteins, Atg11, Atg19, Atg23 and Atg27, as the core minimal machinery necessary and sufficient for the trafficking of Atg9 to the PAS. Atg23 and Atg27 function in the formation of the Atg9 peripheral structures. Overexpression of Atg9 can bypass the need for Atg23, suggesting that the amount of Atg9 in each peripheral structure is a critical factor in their targeting to the PAS. In contrast, overexpression of Atg23 or Atg27 interferes with Atg9 trafficking, suggesting that these proteins must be present in the appropriate stoichiometry in order to function properly. These data allow us to resolve existing controversies regarding the role of Atg23 and Atg27, and propose a model that ties together previous observations regarding the role of Atg9 in autophagosome formation.
Drawing It Out
Authors: Geismar Haidy
Published: November 2014

The fieldwork sketches of Arthur Bernard Deacon, made in Vanuatu in 1926–27, give us insight into the early methodologies of social anthropology and into the role of images in anthropological ways of thinking. Here I develop a perspective on field sketches that explores them not only as visual mediations of the fieldworker's subjectivity, but also as genre pieces that indicate very particular forms of training in “how to see.” I draw out the visual conventions, ways of thinking and seeing, that underscore the different strategies that Deacon used in his drawing.
Jai Bhim Comrade and the Politics of Sound in Urban Indian Visual Culture
Authors: Matzner Deborah
Published: November 2014

Indian documentary filmmaker Anand Patwardhan's latest release Jai Bhim Comrade (2012), which depicts protest music employed by the Dalit (previously “Untouchable”) movement in Maharashtra, presents challenges to the ways in which Patwardhan's work has been characterized. Key among these are the sonic practices in which Dalits in the film engage to assert presence and agency in defiance of their caste subjugation. Situating these practices in the everyday sonic ecologies of Indian cities, I think through the importance of sound to the study of South Asian visual culture and documentary, and interrogate the primacy of the visual in scholarship on visual culture.
Inking a Past; Visualization as a Shedding of Uncertainty
Authors: Westin Jonathan
Published: November 2014

This article explores how an idea about the past enters a visualization studio, and the processes by which it is transformed by the techniques of visual representation put in place to make possible the creation of inscriptions and sketches. It focuses on the formation of a fact around a series of inscriptions, as the idea is moved between a number of actants and in the process sheds all traces of uncertainty. The actions of the artists, as they interact with each other, the client and the archaeologists, are at center. As representations create ideas about the past and cement those ideas in society, one cannot separate popular visual representations from the world of science. The processes of their construction hidden from the recipient, they survive the theories that once brought them into being. As a method to describe the making of a visual representation, this article makes use of the actor–network theory concepts ofenrollment,inscription,negotiation, andtranslationto follow an idea into image and make the layers of translation in which image production is wrapped somewhat less opaque.
Sudden death of a horse with supraventricular tachycardia following oral administration of flecainide acetate
Authors: Dembek Katarzyna A. , Hurcombe Samuel D.A. , Schober Karsten E. , Toribio Ramiro E.
Published: November 2014

Objective

To describe a case of supraventricular tachycardia and sudden death in a horse following administration of flecainide acetate.

Case Summary

An 8‐year‐old Hanoverian warmblood gelding was treated for chronic, naturally occurring, supraventricular tachycardia with digoxin, procainamide hydrochloride, quinidine sulfate, and flecainide acetate. After oral administration of flecainide, polymorphic ventricular tachycardia (torsades de pointes) and ventricular fibrillation developed, leading to cardiovascular collapse and death.

New or Unique Information Provided

Atrial fibrillation is the most commonly diagnosed dysrhythmia associated with poor performance in horses, while atrial tachycardia is rarely documented. Here, we describe a case of sudden death in a horse with atrial tachycardia following the oral administration of flecainide acetate, after the lack of response to other antiarrhythmic drugs. Information provided in this case report is new and will make clinicians aware of the potential complications of flecainide alone or in combination with other drugs, in horses with cardiac dysrhythmias.
Selmer groups and class groups
Authors: Česnavičius Kęstutis
Published: November 2014

Let $A$ be an abelian variety over a global field $K$ of characteristic $p\geqslant 0$. If $A$ has nontrivial (respectively full) $K$-rational $l$-torsion for a prime $l\neq p$, we exploit the fppf cohomological interpretation of the $l$-Selmer group $\text{Sel}_{l}\,A$ to bound $\#\text{Sel}_{l}\,A$ from below (respectively above) in terms of the cardinality of the $l$-torsion subgroup of the ideal class group of $K$. Applied over families of finite extensions of $K$, the bounds relate the growth of Selmer groups and class groups. For function fields, this technique proves the unboundedness of $l$-ranks of class groups of quadratic extensions of every $K$ containing a fixed finite field $\mathbb{F}_{p^{n}}$ (depending on $l$). For number fields, it suggests a new approach to the Iwasawa ${\it\mu}=0$ conjecture through inequalities, valid when $A(K)[l]\neq 0$, between Iwasawa invariants governing the growth of Selmer groups and class groups in a $\mathbb{Z}_{l}$-extension.
Developmentally regulated neurosteroid synthesis enhances GABAergic neurotransmission in mouse thalamocortical neurones
Authors: Brown Adam R. , Herd Murray B. , Belelli Delia , Lambert Jeremy J.
Published: November 2014

Key points

During neuronal development synaptic events mediated by GABAA receptors are progressively reduced in their duration, allowing for rapid and precise network function.

Here we focused on ventrobasal thalamocortical neurones, which contribute to behaviourally relevant oscillations between thalamus and cortex.

We demonstrate that the developmental decrease in the duration of inhibitory phasic events results predominantly from a precisely timed loss of locally produced neurosteroids, which act as positive allosteric modulators of the GABAA receptor.

The mature thalamus retains the ability to synthesise neurosteroids, thus preserving the capacity to enhance both phasic and tonic inhibition, mediated by synaptic and extrasynaptic GABAA receptors, respectively, in physiological and pathophysiological scenarios associated with perturbed neurosteroid levels.

Our data establish a potent, endogenous mechanism to locally regulate the GABAA receptor function and thereby influence thalamocortical activity.

During brain development the duration of miniature inhibitory postsynaptic currents (mIPSCs) mediated by GABAA receptors (GABAARs) progressively reduces, to accommodate the temporal demands required for precise network activity. Conventionally, this synaptic plasticity results from GABAAR subunit reorganisation. In particular, in certain developing neurones synaptic α2‐GABAARs are replaced by α1‐GABAARs. However, in thalamocortical neurones of the mouse ventrobasal (VB) thalamus, the major alteration to mIPSC kinetics occurs on postnatal (P) day 10, some days prior to the GABAAR isoform change. Here, whole‐cell voltage‐clamp recordings from VB neurones of mouse thalamic slices revealed that early in postnatal development (P7–P8), the mIPSC duration is prolonged by local neurosteroids acting in a paracrine or autocrine manner to enhance GABAAR function. However, by P10, this neurosteroid ‘tone’ rapidly dissipates, thereby producing brief mIPSCs. This plasticity results from a lack of steroid substrate as pre‐treatment of mature thalamic slices (P20–24) with the GABAAR‐inactive precursor 5α‐dihydroprogesterone (5α‐DHP) resulted in markedly prolonged mIPSCs and a greatly enhanced tonic conductance, mediated by synaptic and extrasynaptic GABAARs, respectively. In summary, endogenous neurosteroids profoundly influence GABAergic neurotransmission in developing VB neurones and govern a transition from slow to fast phasic synaptic events. Furthermore, the retained capacity for steroidogenesis in the mature thalamus raises the prospect that certain physiological or pathophysiological conditions may trigger neurosteroid neosynthesis, thereby providing a local mechanism for fine‐tuning neuronal excitability.
Defining inhibitory neurone function in respiratory circuits: opportunities with optogenetics?
Authors: Abdala Ana Paula , Paton Julian F. R. , Smith Jeffrey C.
Published: November 2014

Pharmacological and mathematical modelling studies support the view that synaptic inhibition in mammalian brainstem respiratory circuits is essential for generating normal and stable breathing movements. GABAergic and glycinergic neurones are known components of these circuits but their precise functional roles have not been established, especially within key microcircuits of the respiratory pre‐Bötzinger (pre‐BötC) and Bötzinger (BötC) complexes involved in phasic control of respiratory pump and airway muscles. Here, we review briefly current concepts of relevant complexities of inhibitory synapses and the importance of synaptic inhibition in the operation of these microcircuits. We highlight results and limitations of classical pharmacological studies that have suggested critical functions of synaptic inhibition. We then explore the potential opportunities for optogenetic strategies that represent a promising new approach for interrogating function of inhibitory circuits, including a hypothetical wish list for optogenetic approaches to allow expedient application of this technology. We conclude that recent technical advances in optogenetics should provide a means to understand the role of functionally select and regionally confined subsets of inhibitory neurones in key respiratory circuits such as those in the pre‐BötC and BötC.
Constitutive Relations and Parameter Estimation for Finite Deformations of Viscoelastic Adhesives
Authors: Antoine G. O. , Batra R. C.
Published: November 2014

We propose a constitutive relation for finite deformations of nearly incompressible isotropic viscoelastic rubbery adhesives assuming that the Cauchy stress tensor can be written as the sum of elastic and viscoelastic parts. The former is derived from a stored energy function and the latter from a hereditary type integral. Using Ogden’s expression for the strain energy density and the Prony series for the viscoelastic shear modulus, values of material parameters are estimated by using experimental data for uniaxial tensile and compressive cyclic deformations at different constant engineering axial strain rates. It is found that values of material parameters using the loading part of the first cycle, the complete first cycle, and the complete two loading cycles are quite different. Furthermore, the constitutive relation with values of material parameters determined from the monotonic loading during the first cycle of deformations cannot well predict even deformations during the unloading portion of the first cycle. The developed constitutive relation is used to study low-velocity impact of polymethylmethacrylate (PMMA)/adhesive/polycarbonate (PC) laminate. The three sets of values of material parameters for the adhesive seem to have a negligible effect on the overall deformations of the laminate. It is attributed to the fact that peak strain rates in the severely deforming regions are large, and the corresponding stresses are essentially unaffected by the long time response of the adhesive.
Electrochemical Characterization of Synthesized Ni–Co and Ni–Co–Fe Electrodes for Methanol Fuel Cell
Authors: Paul Subir , Naimuddin Sk
Published: November 2014

Pt based materials having high electrocatalytic properties are normally used for the electrodes of the fuel cell. But the cost of the material limits the commercialization of alcoholic fuel cell. Non-Pt based metals and alloys as electrode materials for methyl alcohol fuel cells have been investigated with an aim of finding high electrocatalytic surface property for the faster electrode reactions. Electrodes were fabricated by electrodeposition on pure Al foil, from an electrolyte of Ni, Co, and Fe salts. The optimum condition of electrodeposition was found by a series of experiments, varying the chemistry of the electrolyte, pH, temperature, current, and cell potential. Polarization study of the coated Ni–Co or Ni–Co–Fe alloy on pure Al was found to exhibit high exchange current density, indicating an improved electrocatalytic surface with faster charge–discharge reactions at anode and cathode and low overvoltage. Electrochemical impedance studies on the coated and uncoated surface clearly showed that the polarization resistance and impedance were decreased by Ni–Co or N–Co–Fe coating. X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), and atomic absorption spectroscopy (AAS) studies confirmed the presence of alloying elements and constituents of the alloy. The morphology of the deposits from scanning electron microscope (SEM) images indicated that the electrode surface was a three-dimensional space which increased the effective surface area for the electrode reactions to take place.
Trashing Misfolded Membrane Proteins
Authors: Hurtley Stella M.
Published: November 2014

A branch of the endoplasmic reticulum–associated protein degradation system degrades inner nuclear membrane proteins in yeast.
Knowing Where to S-Nitrosylate
Authors: Gough Nancy R.
Published: November 2014

The calcium-regulated inflammatory mediators S100A8 and S100A9 are necessary for site-specific S-nitrosylation.
Cyclin, Notch, and ALL
Authors: Ferrarelli Leslie K.
Published: November 2014

Cyclin C functions as a tumor suppressor in T cell acute lymphoblastic leukemia by inhibiting Notch signaling.
Testing Tuberculosis Drug Efficacy in a Zebrafish High-Throughput Translational Medicine Screen
Authors: Ordas Anita , Raterink Robert-Jan , Cunningham Fraser , Jansen Hans J. , Wiweger Malgorzata I. , Jong-Raadsen Susanne , Bos Sabine , Bates Robert H. , Barros David , Meijer Annemarie H. , Vreeken Rob J. , Ballell-Pages Lluís , Dirks Ron P. , Hankemeier Thomas , Spaink Herman P.
Published: November 2014

The translational value of zebrafish high-throughput screens can be improved when more knowledge is available on uptake characteristics of potential drugs. We investigated reference antibiotics and 15 preclinical compounds in a translational zebrafish-rodent screening system for tuberculosis. As a major advance, we have developed a new tool for testing drug uptake in the zebrafish model. This is important, because despite the many applications of assessing drug efficacy in zebrafish research, the current methods for measuring uptake using mass spectrometry do not take into account the possible adherence of drugs to the larval surface. Our approach combines nanoliter sampling from the yolk using a microneedle, followed by mass spectrometric analysis. To date, no single physicochemical property has been identified to accurately predict compound uptake; our method offers a great possibility to monitor how any novel compound behaves within the system. We have correlated the uptake data with high-throughput drug-screening data from
Mycobacterium marinum
-infected zebrafish larvae. As a result, we present an improved zebrafish larva drug-screening platform which offers new insights into drug efficacy and identifies potential false negatives and drugs that are effective in zebrafish and rodents. We demonstrate that this improved zebrafish drug-screening platform can complement conventional models of
in vivo
Mycobacterium tuberculosis
-infected rodent assays. The detailed comparison of two vertebrate systems, fish and rodent, may give more predictive value for efficacy of drugs in humans.
Molecular Characterization of Fluoroquinolone Resistance in Nontypeable Haemophilus influenzae Clinical Isolates
Authors: Puig Carmen , Tirado-Vélez José Manuel , Calatayud Laura , Tubau Fe , Garmendia Junkal , Ardanuy Carmen , Marti Sara , de la Campa Adela G. , Liñares Josefina
Published: November 2014

Nontypeable
Haemophilus influenzae
(NTHi) is a common cause of respiratory infections in adults, who are frequently treated with fluoroquinolones. The aims of this study were to characterize the genotypes of fluoroquinolone-resistant NTHi isolates and their mechanisms of resistance. Among 7,267
H. influenzae
isolates collected from adult patients from 2000 to 2013, 28 (0.39%) were ciprofloxacin resistant according to Clinical and Laboratory Standards Institute (CLSI) criteria. In addition, a nalidixic acid screening during 2010 to 2013 detected five (0.23%) isolates that were ciprofloxacin susceptible but nalidixic acid resistant. Sequencing of their quinolone resistance-determining regions and genotyping by pulse-field gel electrophoresis and multilocus sequence typing of the 25 ciprofloxacin-resistant isolates available and all 5 nalidixic acid-resistant isolates were performed. In the NTHi isolates studied, two mutations producing changes in two GyrA residues (Ser84, Asp88) and/or two ParC residues (Ser84, Glu88) were associated with increased fluoroquinolone MICs. Strains with one or two mutations (
n
= 15) had ciprofloxacin and levofloxacin MICs of 0.12 to 2 μg/ml, while those with three or more mutations (
n
= 15) had MICs of 4 to 16 μg/ml. Long persistence of fluoroquinolone-resistant strains was observed in three chronic obstructive pulmonary disease patients. High genetic diversity was observed among fluoroquinolone-resistant NTHi isolates. Although fluoroquinolones are commonly used to treat respiratory infections, the proportion of resistant NTHi isolates remains low. The nalidixic acid disk test is useful for detecting the first changes in GyrA or in GyrA plus ParC among fluoroquinolone-susceptible strains that are at a potential risk for the development of resistance under selective pressure by fluoroquinolone treatment.
Arthritis and Benznidazole: More Closely Related than We Thought
Authors: Aldasoro E. , Pinazo M. J. , Oliveira I. , Munoz J. , Posada E. , Requena-Méndez A. , Serret N. , Gascon J.
Published: November 2014

Chagas disease is a parasitic infection that leads to a significant public health problem in countries where the disease is endemic and where it is nonendemic. Benznidazole is the most commonly used drug for the etiological treatment of Chagas disease. Patients treated with benznidazole suffer frequent adverse drug reactions. Although arthralgia is common, arthritis has been reported as a very rare side effect. The objective of this study was to describe arthritis in a cohort of
Trypanosoma cruzi
-infected patients treated with benznidazole.
Mechanism of β-Lactam Action in Streptococcus pneumoniae: the Piperacillin Paradox
Authors: Philippe Jules , Gallet Benoit , Morlot Cécile , Denapaite Dalia , Hakenbeck Regine , Chen Yuxin , Vernet Thierry , Zapun André
Published: November 2014

The human pathogen
Streptococcus pneumoniae
has been treated for decades with β-lactam antibiotics. Its resistance is now widespread, mediated by the expression of mosaic variants of the target enzymes, the penicillin-binding proteins (PBPs). Understanding the mode of action of β-lactams, not only in molecular detail but also in their physiological consequences, will be crucial to improving these drugs and any counterresistances. In this work, we investigate the piperacillin paradox, by which this β-lactam selects primarily variants of PBP2b, whereas its most reactive target is PBP2x. These PBPs are both essential monofunctional transpeptidases involved in peptidoglycan assembly. PBP2x participates in septal synthesis, while PBP2b functions in peripheral elongation. The formation of the “lemon”-shaped cells induced by piperacillin treatment is consistent with the inhibition of PBP2x. Following the examination of treated and untreated cells by electron microscopy, the localization of the PBPs by epifluorescence microscopy, and the determination of the inhibition time course of the different PBPs, we propose a model of peptidoglycan assembly that accounts for the piperacillin paradox.
Carbapenem-Resistant Klebsiella pneumoniae Urinary Tract Infection following Solid Organ Transplantation
Authors: Brizendine Kyle D. , Richter Sandra S. , Cober Eric D. , van Duin David
Published: November 2014

Carbapenem-resistant
Klebsiella pneumoniae
(CRKP) is an emerging pathogen with a devastating impact on organ transplant recipients (OTRs). Data describing urinary tract infections (UTIs) due to CRKP, compared to extended-spectrum β-lactamase (ESBL)-producing and susceptible
K. pneumoniae
, are lacking. We conducted a retrospective cohort study comparing OTRs with a first episode of UTI due to CRKP, ESBL-producing
K. pneumoniae
, or susceptible
K. pneumoniae
. We identified 108 individuals; 22 (20%) had UTIs due to CRKP, 22 (20%) due to ESBL-producing
K. pneumoniae
, and 64 (60%) due to susceptible
K. pneumoniae
. Compared to susceptible
K. pneumoniae
(27%), patients with UTIs due to CRKP or ESBL-producing
K. pneumoniae
were more likely to have a ≥24-hour stay in the intensive care unit (ICU) before or after development of the UTI (64% and 77%, respectively;
P
< 0.001). Among 105/108 hospitalized patients (97%), the median lengths of stay prior to UTI with CRKP or ESBL-producing
K. pneumoniae
(7 and 8 days, respectively) were significantly longer than that for susceptible
K. pneumoniae
(1 day;
P
< 0.001). Clinical failure was observed for 8 patients (36%) with CRKP, 4 (18%) with ESBL-producing
K. pneumoniae
, and 9 (14%) with susceptible
K. pneumoniae
(
P
= 0.073). Microbiological failure was seen for 10 patients (45%) with CRKP, compared with 2 (9%) with ESBL-producing
K. pneumoniae
and 2 (3%) with susceptible
K. pneumoniae
(
P
< 0.001). In multivariable logistic regression analyses, CRKP was associated with greater odds of microbiological failure (versus ESBL-producing
K. pneumoniae
: odds ratio [OR], 9.36, 95% confidence interval [CI], 1.94 to 72.1; versus susceptible
K. pneumoniae
: OR, 31.4, 95% CI, 5.91 to 264). In conclusion, CRKP is associated with ICU admission, long length of stay, and microbiological failure among OTRs with UTIs. Greater numbers are needed to determine risk factors for infection and differences in meaningful endpoints associated with carbapenem resistance.