bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytokinin modulates proteomic, transcriptomic and growth responses to temperature shocks in Arabidopsis
Authors: ČERNÝ MARTIN , JEDELSKÝ PETR L. , NOVÁK JAN , SCHLOSSER ANDREAS , BRZOBOHATÝ BŘETISLAV
Published: January 2014

As sessile organisms, plants must sense environmental conditions and adjust their growth and development processes accordingly, through adaptive responses regulated by various internal factors, including hormones. A key environmental factor is temperature, but temperature‐sensing mechanisms are not fully understood despite intense research. We investigated proteomic responses to temperature shocks (15 min cold or heat treatments) with and without exogenous applications of cytokinin in Arabidopsis. Image and mass spectrometric analysis of the two‐dimensionally separated proteins detected 139 differentially regulated spots, in which 148 proteins were identified, most of which have not been previously linked to temperature perception. More than 70% of the temperature‐shock response proteins were modulated by cytokinin, mostly in a similar manner as heat shock. Data mining of previous transcriptomic datasets supported extensive interactions between temperature and cytokinin signalling. The biological significance of this finding was tested by assaying an independent growth response of Arabidopsis seedlings to heat stress: hypocotyl elongation. This response was strongly inhibited in mutants with deficiencies in cytokinin signalling or endogenous cytokinin levels. Thus, cytokinins may directly participate in heat signalling in plants. Finally, large proportions of both temperature‐shock and cytokinin responsive proteomes co‐localize to the chloroplast, which might therefore host a substantial proportion of the temperature response machinery.
Anterior cingulate cortex and cerebellar hemisphere neurometabolite changes in depression treatment: A 1H magnetic resonance spectroscopy study
Authors: Chen Li‐Ping , Dai Hai‐Yang , Dai Zhuo‐Zhi , Xu Chong‐Tao , Wu Ren‐Hua
Published: January 2014

Aim

We utilized single‐voxel 1H magnetic resonance spectroscopy to determine biochemical abnormalities related to major depressive disorder (MDD) in the bilateral dorsolateral prefrontal cortex, anterior cingulate cortex (ACC), and cerebellar hemisphere before and after antidepressant treatment.

Methods

Fifteen adult MDD patients and 15 age‐ and sex‐matched healthy controls were involved. Magnetic resonance spectroscopy of the brain was conducted in all subjects at the beginning of the study and the depressed subjects were reassessed after 8 weeks of antidepressant treatment.

Results

At baseline, N‐acetyl aspartate (NAA), total glutamine plus glutamate (Glx) and myo‐inositol (MI) levels in the bilateral ACC were significantly lower in MDD patients than in controls (P < 0.05/3). MI in the bilateral cerebellar hemisphere were also decreased in patients compared with controls. After the treatment, the lower NAA, Glx and MI in ACC were normalized in MDD patients and the NAA and Glx increased compared to baseline values. The MI levels in the bilateral cerebellar hemisphere were also normalized in patients. MI and choline levels in the right cerebellar hemisphere were elevated compared to those at baseline.

Conclusion

Our study suggests that metabolic abnormalities in the ACC and cerebellar hemisphere are implicated in MDD. Antidepressants may alter the local metabolic abnormalities in these areas.
Definition and stabilisation of the quiescent centre in rice roots
Authors: Ni J. , Shen Y. , Zhang Y. , Wu P.
Published: January 2014

The definition of a quiescent centre (QC) in Arabidopsis has been adequately demonstrated. However, the QC structure of rice has not yet been described in detail. In this research, using histological and marker gene expression analysis, we concluded that the rice QC is very small, and is similar to that of Arabidopsis. Next we investigated the stability of the rice QC during nutrient deficiencies or external hormone treatments, and found that nutrient deficiencies, auxin treatment and cytokinin treatment did not change the cell patterns of the QC. However, ethylene induced irregular transverse cell divisions in the QC and changed formative cell divisions of the ground tissue stem cells (GTSCs) in rice.
Auxin conjugated to fluorescent dyes – a tool for the analysis of auxin transport pathways
Authors: Sokołowska K. , Kizińska J. , Szewczuk Z. , Banasiak A.
Published: January 2014

Auxin is a small molecule involved in most processes related to plant growth and development. Its effect usually depends on the distribution in tissues and the formation of concentration gradients. Until now there has been no tool for the direct tracking of auxin transport at the cellular and tissue level; therefore the majority of studies have been based on various indirect methods. However, due to their various restrictions, relatively little is known about the relationship between various pathways of auxin transport and specific developmental processes. We present a new research tool: fluorescently labelled auxin in the form of a conjugate with two different fluorescent tracers, FITC and RITC, which allows direct observation of auxin transport in plant tissues. Chemical analysis and biological tests have shown that our conjugates have auxin‐like biological activity and transport; therefore they can be used in all experimental systems as an alternative to IAA. In addition, the conjugates are a universal tool that can be applied in studies of all plant groups and species. The conjugation procedure presented in this paper can be adapted to other fluorescent dyes, which are constantly being improved. In our opinion, the conjugates greatly expand the possibilities of research concerning the role of auxin and its transport in different developmental processes in plants.
Host specificity and genetic diversity of race 4 strains of Ralstonia solanacearum
Authors: Kumar A. , Prameela T. P. , Suseelabhai R. , Siljo A. , Anandaraj M. , Vinatzer B. A.
Published: January 2014

Ralstonia solanacearum race 4 isolates were obtained from Zingiberaceae plants in India during bacterial wilt outbreaks. Polyphasic phenotypic and genotypic analysis revealed intraracial diversity and dominance of biovar 3 over biovar 4. Biovar 3 strains were isolated from very severely wilted Zingiberaceae plants in the field and found to be present across diverse geographical, host and seasonal boundaries. It was hypothesized that these isolates belong to a single, ‘fast wilting’, lineage. Using one ‘fast wilting’ isolate in controlled inoculations, rapid wilt was observed in ginger within 5–7 days. Wilting was also observed in several other closely and distantly related hosts such as turmeric (Curcuma longa), aromatic turmeric (Curcuma aromatica), black turmeric (Curcuma caesia), sand ginger (Kaempferia galanga), white turmeric (Curcuma zeodaria), awapuhi (Zingiber zerumbet), greater galangal (Alpinia galanga), globba (Globba sp.), small cardamom (Elettaria cardamomum) and large cardamom (Ammomum subulatum) of the Zingiberaceae family, and in tomato (Solanum lycopersicum). Molecular analysis, including multiplex PCR‐based phylotyping, sequence analysis of 16S rDNA, 16–23S intergenic spacer and the recN gene, and multilocus sequence typing, revealed minimal differences between fast wilting isolates, confirming that almost all belong to the same lineage. Biovar 4 was isolated from plants showing slow wilt progression and self‐limiting wilting in restricted geographical locations instead, and was identified to be genetically distinct from the fast wilting biovar 3 isolates. To the authors' knowledge, this is the first report of host range and genetic analysis of R. solanacearum race 4 in India.
Components of different signalling pathways regulated by a new orthologue of AtPROPEP1 in tomato following infection by pathogens
Authors: Trivilin A. P. , Hartke S. , Moraes M. G.
Published: January 2014

Plants express different defence mechanisms in response to pathogens. Understanding the recognition of pathogen‐associated molecular patterns (PAMPs) by specific receptors, and the role of endogenous signals such as AtPep1 that regulate expression of genes in Arabidopsis thaliana, has aided the understanding of the defence mechanisms in different species. The aim of this study was to identify possible orthologous sequences of AtPROPEPs in tomato (Solanum lycopersicum) and characterize its role in resistance to necrotrophic pathogens. The presence of an orthologue of the A. thaliana AtPROPEP1 gene in S. lycopersicum, SlPROPEP, by in silico analysis, is reported here. This has 96% identity with the C‐terminal region of a previously described potato peptide, another possible orthologue of AtPep1. A virus‐induced gene silencing (VIGS) system was employed to investigate the role of the SlPROPEP. Silencing of SlPROPEP in tomato made plants more susceptible to Pythium dissotocum; approximately 30% of SlPROPEP‐silenced plants showed stem constriction compared with 4% in control plants. Furthermore, quantification of P. dissotocum by qPCR revealed that the increase in symptom severity in SlPROPEP‐silenced plants was associated with a 15 times increase in growth of the pathogen compared to control plants. Silencing of SlPROPEP also resulted in decreased expression of genes involved in plant defence against pathogens, such as PR‐1, PR‐5, ERF1, LOX‐D and DEF2. These results suggest that SlPROPEP is involved in tomato resistance to P. dissotocum and probably acts as a pathogen‐associated molecular pattern through signalling pathways mediated by jasmonic acid/ethylene (JA/ET).
The Emerging New Concept of Services in the System of National Accounts and the Balance of Payments
Authors: Broussolle Damien
Published: January 2014

The new manuals of the National Accounts and of the Balance of Payments are implementing new features regarding services. The paper points out the emergence of an innovative concept of services which is highly relevant but whose consequences may not be fully understood. This new perspective helps to focus on the true nature of services, but it also redefines the borders between services and goods. The paper addresses the problems left unresolved, or brought in, by the revisions. Furthermore, it studies the treatment of non‐financial services in the BOP as compared to the SNA. Although the two approaches have been rendered more compatible, the BOP still incorporates several inconsistencies. The hesitancy to completely implement the new services definition tends to somewhat blur the measurement of trade in services.
Overlay removable denture for treatment of worn teeth
Authors: Beyth Nurit , Tamari Israel , Buller Sharon Anat
Published: January 2014

Rehabilitation of partially edentulous patients with excessively worn dentitions can be challenging. Factors including medical history as well as the cost of the treatment and patient wishes for simpler approaches must be considered. This manuscript describes the use of an overlay partial denture to treat patients with excessive wear of the maxillary teeth. We describe a technique to restore severely worn teeth using heat‐cured acrylic as part of a partial or full denture. Minimal preparations of the teeth are required, and the restoration provides protection from further wear, and stabilizes the occlusion. This solution was functionally and esthetically suitable to the patients. The technique can be used in medically complex patients where extractions are contraindicated, such as post radiation therapy or bisphosphonate treatment.
Facies architecture of asymmetrical branching distributary channels: Cretaceous Ferron Sandstone, Utah, USA
Authors: Li Yangyang , Bhattacharya Janok
Published: January 2014

Distributary channel systems are an important component of deltaic systems, but details of their branching pattern, stream‐order, internal variability and relation with adjacent levée, bay and bayhead delta are rather poorly documented in ancient examples. Photomosaic and measured sections collected along a gooseneck‐shaped canyon in southern Utah allow direct mapping of the branching pattern of an ancient distributary system. The main channel belt is ca 250 m wide and narrows to ca 200 m downstream of the branching point. A subordinate channel belt, ca 80 m wide, branches off of the main channel, forming a distinctly asymmetrical branching pattern. Water discharge in the main channel is estimated to be 85 to 170 m3 sec−1. Comparison with palaeodischarge estimates of trunk rivers mapped in previous studies suggests that the branching documented in this study probably is a fourth‐order split. The distributary channels are characterized by a U‐shaped geometry filled with medium‐grained, cross‐bedded sandstone, and are dominated by lateral accretion, suggesting limited lateral migration and moderate sinuosity. Tidally influenced facies and limited trace fossils indicate direct marine influence. The distributary channels erode into adjacent levée and underlying heterolithic bay‐fill deposits, and the marine influence suggests that they were deposited on a lower delta plain, rather than on a non‐marine floodplain. The subordinate channel fed a bayhead delta, suggesting that it was formed by a partial avulsion, rather than bifurcation around a mouth bar, as is more characteristic of terminal distributary channels. Channel‐floor drapes, bar‐accretion drapes and abandoned channel fills within the sandstone channel belts represent the most important heterogeneity from the perspective of reservoir characterization.
Phylogenetics and evolutionary morphology of the Neotropical true bug genus Epipolops (Hemiptera: Heteroptera: Geocoridae)
Authors: RENGIFO‐CORREA LAURA , BRAILOVSKY HARRY , HENRY THOMAS J. , MORRONE JUAN J.
Published: January 2014

Species of Epipolops Herrich‐Schaeffer (Hemiptera: Geocoridae), comprising the largest genus of Pamphantinae, are among the most bizarre true bugs because of their striking morphology. To elucidate evolutionary morphology in Epipolops, a phylogenetic analysis was performed using 17 species and 36 adult morphological characters. Two cladograms were obtained under equal and implied weight analyses, showing slight differences between them. Two new species, E. stridulatus sp.n. and E. univallensis sp.n., are described, and E. meridionalis Pirán is resurrected from synonymy with E. frondosus Herrich‐Schaeffer. A key to the known species of Epipolops is provided. The systematic relevance of the unique characters of the genus is discussed and the sequence of character state transformations for both the anterior and posterior lateral processes of the pronotum are optimized on the cladogram obtained under implied weights. Species of Epipolops are found in the Neotropical region and the Mexican Transition Zone, with some clades and species restricted to certain South American subregions.

This published work has been registered in ZooBank, http://zoobank.org/urn:lsid:zoobank.org:pub:CB72D5DA‐D86B‐4B91‐93A2‐88894F7120C9.
The novel allele, HLA‐B*08:113, identified in a German cord blood donor and his mother
Authors: Strobel J. , Ringwald J. , Hauck‐Dlimi B. , Eckstein R. , Zingsem J.
Published: January 2014

The novel allele HLA‐B*08:113 identified in two related individuals of Caucasian origin is described.
A novel KIR3DL1*0070104 allele found in individuals from Asia
Authors: Yindom L.‐M. , Wang L. , Dong T. , Rowland‐Jones S.L.
Published: January 2014

KIR3DL1*0070104 differs from KIR3DL1*0070101 at position 13889 (T > G) in the 3′UTR region of KIR3DL1/S1 locus.
Tim‐3 expression on peripheral monocytes and CD3+CD16/CD56+natural killer‐like T cells in patients with chronic hepatitis B
Authors: Rong Y.‐H. , Wan Z.‐H. , Song H. , Li Y.‐L. , Zhu B. , Zang H. , Zhao Y. , Liu H.‐L. , Zhang A.‐M. , Xiao L. , Xin S.‐J. , You S.‐L.
Published: January 2014

Hepatitis B virus (HBV) infection is one of the major causes of chronic liver inflammation. Tim‐3 acts as a negative regulatory molecule and plays a critical role in immune tolerance. In the current study, we investigated Tim‐3 expression on peripheral monocytes and CD3+CD16/CD56+ natural killer like T (NKT‐like) cells in chronic hepatitis B (CHB) patients. Peripheral blood mononuclear cells (PBMCs) were isolated from 52 CHB patients and 60 healthy controls. Tim‐3+CD14+ cells and Tim‐3+CD3+CD16/CD56+ cells were analyzed by flow cytometry. Results showed that expression of Tim‐3 was significantly increased on both the monocytes and NKT‐like cells in CHB patients than in controls (P = 0.002 and P < 0.001, respectively). Tim‐3 levels on monocytes and NKT‐like cells were further upregulated in patients with acute‐on‐chronic liver failure (ACLF). In addition, we assessed the correlation of Tim‐3 expression with levels of alanine aminotransferase (ALT) and tumor necrosis factor alpha (TNF‐α). Data revealed that Tim‐3 expression on both monocytes and NKT‐like cells was positively correlated with level of ALT (r = 0.59, P < 0.001, and r = 0.60, P < 0.001, respectively), whereas Tim‐3 expression on NKT‐like cells was negatively correlated with serum level of TNF‐α (r = −0.54, P < 0.001) in CHB patients. Our results suggest that Tim‐3 may play important roles in the pathogenesis of CHB.
Implication of HLA‐G 3′ untranslated region polymorphisms in human papillomavirus infection
Authors: Bortolotti D. , Gentili V. , Rotola A. , Di Luca D. , Rizzo R.
Published: January 2014

Human papillomavirus (HPV) infection is involved in cervical lesion development. It interferes with host immune response and modifies the expression of human leukocyte antigen‐G (HLA‐G), a nonclassical HLA‐I antigen with immune‐inhibitory functions. We analyzed the frequencies of two HLA‐G 3′ untranslated region polymorphisms (14 bp ins/del, +3142C>G), involved in HLA‐G modulation, in 33 condyloma acuminatum, 14 low grade squamous intraepithelial lesion and 100 invasive cervical cancer (ICC) HPV infected patients. We showed the involvement of HLA‐G polymorphisms in HPV infection and lesion development, and suggested that 14 bp del allele promotes high‐risk HPV infection, with del/C haplotype associated with ICC development. On the basis of these evidences, HLA‐G polymorphisms could represent a risk factor in HPV positive subjects.
A comprehensive analysis of constitutive naturally processed and presented HLA‐C*04:01 (Cw4) – specific peptides
Authors: Schittenhelm R. B. , Dudek N. L. , Croft N. P. , Ramarathinam S. H. , Purcell A. W.
Published: January 2014

The human B lymphoblastoid cell line C1R is widely regarded as human leukocyte antigen‐A (HLA‐A)/HLA‐B negative and is therefore frequently exploited as a recipient cell line to study HLA class I functions. However, the normal levels of HLA‐C*04:01 often hamper the investigation of introduced HLA class I allomorphs, which is particularly evident in sensitive applications such as mass spectrometry. Here we describe the comprehensive analysis of endogenous HLA‐C*04:01 ligands expressed on the surface of C1R cells to (i) define a large sequence dataset of HLA‐C*04:01 ligands, to (ii) refine the HLA‐C*04:01 peptide‐binding motif and (iii) to provide a resource that allows discrimination between peptides bound to introduced HLA class I subtypes and to the endogenous HLA‐C*04:01 molecules.
Photoresponse diversity among the five types of intrinsically photosensitive retinal ganglion cells
Authors: Zhao Xiwu , Stafford Ben K. , Godin Ashley L. , King W. Michael , Wong Kwoon Y.
Published: January 2014

Key points

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are a rare population of retinal output neurons that drives subconscious physiological responses to light, e.g. pupillary constriction, synchronization of daily rhythms to the light–dark cycle and regulation of hormone secretion.

This study investigated the functional diversity among the five known types of ipRGCs, named M1–M5.

We found that M2–M5 cells could detect spatial differences in light intensity, implicating an ability to analyse the form of visual stimuli.

All five ipRGC types responded robustly to moving lights, and M1–M4 cells appeared to respond optimally to different speeds, suggesting they might analyse the speed of motion.

M1–M4 cells were shown to project to the superior colliculus, a brain area known to detect novel objects in the visual scene, suggesting that the form and motion information signalled by these four types of ipRGCs could contribute to this visual function.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate non‐image‐forming visual responses, including pupillary constriction, circadian photoentrainment and suppression of pineal melatonin secretion. Five morphological types of ipRGCs, M1–M5, have been identified in mice. In order to understand their functions better, we studied the photoresponses of all five cell types, by whole‐cell recording from fluorescently labelled ipRGCs visualized using multiphoton microscopy. All ipRGC types generated melanopsin‐based (‘intrinsic’) as well as synaptically driven (‘extrinsic’) light responses. The intrinsic photoresponses of M1 cells were lower threshold, higher amplitude and faster than those of M2–M5. The peak amplitudes of extrinsic light responses differed among the ipRGC types; however, the responses of all cell types had comparable thresholds, kinetics and waveforms, and all cells received rod input. While all five types exhibited inhibitory amacrine‐cell and excitatory bipolar‐cell inputs from the ‘on’ channel, M1 and M3 received additional ‘off’‐channel inhibition, possibly through their ‘off’‐sublamina dendrites. The M2–M5 ipRGCs had centre–surround‐organized receptive fields, implicating a capacity to detect spatial contrast. In contrast, the receptive fields of M1 cells lacked surround antagonism, which might be caused by the surround of the inhibitory input nullifying the surround of the excitatory input. All ipRGCs responded robustly to a wide range of motion speeds, and M1–M4 cells appeared tuned to different speeds, suggesting that they might analyse the speed of motion. Retrograde labelling revealed that M1–M4 cells project to the superior colliculus, suggesting that the contrast and motion information signalled by these cells could be used by this sensorimotor area to detect novel objects and motion in the visual field.
Purinergic inhibitory regulation of murine detrusor muscles mediated by PDGFRα+ interstitial cells
Authors: Lee Haeyeong , Koh Byoung H. , Peri Lauren E. , Sanders Kenton M. , Koh Sang Don
Published: January 2014

Key points

Platelet‐derived growth factor receptor‐α‐positive (PDGFRα+) interstitial cells in detrusor muscles may participate in post‐junctional responses to neurotransmitters.

PDGFRα+ interstitial cells express purinergic receptors (P2Y) and small conductance Ca2+‐activated K+ channels (mainly SK3). ATP elicited large amplitude outward currents and hyperpolarization in PDGFRα+ cells. SK channel blockers and a P2Y1 receptor antagonist blocked responses to ATP.

ATP elicited only minor responses in PDGFRα+ cells of P2ry1−/− mice. ATP elicited transient inward currents in smooth muscle cells and purinergic receptor (P2X) agonists had no effect on PDGFRα+ cells.

A specific P2Y1 receptor blocker decreased electrical field stimulation‐induced relaxation.

Our findings provide an explanation for the purinergic relaxation of detrusor muscles and describe a novel mechanism for inhibitory regulation of bladder muscles that may control detrusor excitability during the filling phase.

Purines induce transient contraction and prolonged relaxation of detrusor muscles. Transient contraction could be due to activation of inward currents in smooth muscle cells, but the mechanism of purinergic relaxation has not been determined. We recently reported a new class of interstitial cells in detrusor muscles and showed that these cells could be identified with antibodies against platelet‐derived growth factor receptor‐α (PDGFRα+ cells). The current density of small conductance Ca2+‐activated K+ (SK) channels in these cells is far higher (∼100 times) than in smooth muscle cells. Thus, we examined purinergic receptor (P2Y) mediated SK channel activation as a mechanism for purinergic relaxation. P2Y receptors (mainly P2ry1 gene) were highly expressed in PDGFRα+ cells. Under voltage clamp conditions, ATP activated large outward currents in PDGFRα+ cells that were inhibited by blockers of SK channels. ATP also induced significant hyperpolarization under current clamp conditions. A P2Y1 agonist, MRS2365, mimicked the effects of ATP, and a P2Y1 antagonist, MRS2500, inhibited ATP‐activated SK currents. Responses to ATP were largely abolished in PDGFRα+ cells of P2ry1−/− mice, and no response was elicited by MRS2365 in these cells. A P2X receptor agonist had no effect on PDGFRα+ cells but, like ATP, activated transient inward currents in smooth muscle cells (SMCs). A P2Y1 antagonist decreased nerve‐evoked relaxation. These data suggest that purines activate SK currents via mainly P2Y1 receptors in PDGFRα+ cells. Our findings provide an explanation for purinergic relaxation in detrusor muscles and show that there are no discrete inhibitory nerve fibres. A dual receptive field for purines provides the basis for inhibitory neural regulation of excitability.
The Algebraic Structure of Spaces of Intervals: Contribution of Svetoslav Markov to Interval Analysis and its Applications
Authors: Anguelov Roumen
Published: January 2014

In Interval Analysis addition of intervals is the usual Minkowski addition of sets. The fact that the additive inverse generally does not exist has been a major obstacle in applications, e.g. constructing narrow enclosures of a solution, and possibly one of the most important mathematical challenges associated with the development of the theory of spaces of intervals. The work on this issue during the last 50-60 years lead to new operations for intervals, extended concepts of interval, setting the interval theory within the realm of algebraic structures more general than group and linear space. This theoretical development was paralleled by development of interval computer arithmetic. Svetoslav Markov was strongly involved in this major development in modern mathematics and he in fact introduced many of the main concepts and theories associated with it.
TRAF6 Stimulates the Tumor-Promoting Effects of TGFβ Type I Receptor Through Polyubiquitination and Activation of Presenilin 1
Authors: Gudey Shyam Kumar , Sundar Reshma , Mu Yabing , Wallenius Anders , Zang Guangxiang , Bergh Anders , Heldin Carl-Henrik , Landström Marene
Published: January 2014

Preventing the cleavage of the TGFβ type I receptor by presenilin 1 could limit prostate tumor growth.
A Ligand-Independent VEGFR2 Signaling Pathway Limits Angiogenic Responses in Diabetes
Authors: Warren Carmen M. , Ziyad Safiyyah , Briot Anaïs , Der Aaron , Iruela-Arispe M. Luisa
Published: January 2014

Hyperglycemia restricts the formation of new blood vessels by preventing VEGFR2 from responding to its angiogenic ligand VEGF.
2013: Signaling Breakthroughs of the Year
Authors: Berndt Jason D. , Gough Nancy R.
Published: January 2014

The year’s highlights include structural insights into signaling proteins, advances in understanding signaling dynamics, and advances in methods for studying cellular regulatory phenomena.
More from mTOR
Authors: Kiberstis Paula A.
Published: January 2014

A drug in clinical use for other disorders delays progression of an untreatable mitochondrial disease in knockout mice.
Counteracting Cannabis
Authors: Stern Peter R.
Published: January 2014

The universal precursor of steroid hormones acts as a negative allosteric modulator of cannabinoid receptors.
Fucosylated Chondroitin Sulfate Inhibits Plasmodium falciparum Cytoadhesion and Merozoite Invasion
Authors: Bastos Marcele F. , Albrecht Letusa , Kozlowski Eliene O. , Lopes Stefanie C. P. , Blanco Yara C. , Carlos Bianca C. , Castiñeiras Catarina , Vicente Cristina P. , Werneck Claudio C. , Wunderlich Gerhard , Ferreira Marcelo U. , Marinho Claudio R. F. , Mourão Paulo A. S. , Pavão Mauro S. G. , Costa Fabio T. M.
Published: January 2014

Sequestration ofPlasmodium falciparum-infected erythrocytes (Pf-iEs) in the microvasculature of vital organs plays a key role in the pathogenesis of life-threatening malaria complications, such as cerebral malaria and malaria in pregnancy. This phenomenon is marked by the cytoadhesion of Pf-iEs to host receptors on the surfaces of endothelial cells, on noninfected erythrocytes, and in the placental trophoblast; therefore, these sites are potential targets for antiadhesion therapies. In this context, glycosaminoglycans (GAGs), including heparin, have shown the ability to inhibit Pf-iE cytoadherence and growth. Nevertheless, the use of heparin was discontinued due to serious side effects, such as bleeding. Other GAG-based therapies were hampered due to the potential risk of contamination with prions and viruses, as some GAGs are isolated from mammals. In this context, we investigated the effects and mechanism of action of fucosylated chondroitin sulfate (FucCS), a unique and highly sulfated GAG isolated from the sea cucumber, with respect toP. falciparumcytoadhesion and development. FucCS was effective in inhibiting the cytoadherence of Pf-iEs to human lung endothelial cells and placenta cryosections under static and flow conditions. Removal of the sulfated fucose branches of the FucCS structure virtually abolished the inhibitory effects of FucCS. Importantly, FucCS rapidly disrupted rosettes at high levels, and it was also able to block parasite development by interfering with merozoite invasion. Collectively, these findings highlight the potential of FucCS as a candidate for adjunct therapy against severe malaria.
High Rate of Fecal Carriage of Extended-Spectrum-β-Lactamase-Producing Escherichia coli in Healthy Children in Gipuzkoa, Northern Spain
Authors: Fernández-Reyes María , Vicente Diego , Gomariz María , Esnal Olatz , Landa Joseba , Oñate Eider , Pérez-Trallero Emilio
Published: January 2014

The prevalence of extended-spectrum-β-lactamase-producing
Enterobacteriaceae
(ESBLPE) was studied in stool samples from 125 8- to 16-month-old healthy children. Twenty-four percent of them and 10.7% of the 318 fecal samples studied yielded extended-spectrum-β-lactamase-producing
Escherichia coli
, with the types being SHV-12, CTX-M-1, CTX-M-14, and TEM-52, the most common types of β-lactamases. This high prevalence of ESBLPE in healthy people, which is to our knowledge the highest currently reported in Europe, may represent a risk for increased infections by these organisms in the future.
Characterization of Klebsiella sp. Strain 10982, a Colonizer of Humans That Contains Novel Antibiotic Resistance Alleles and Exhibits Genetic Similarities to Plant and Clinical Klebsiella Isolates
Authors: Hazen Tracy H. , Zhao LiCheng , Sahl Jason W. , Robinson Gwen , Harris Anthony D. , Rasko David A. , Johnson J. Kristie
Published: January 2014

A unique
Klebsiella
species strain, 10982, was cultured from a perianal swab specimen obtained from a patient in the University of Maryland Medical Center intensive care unit.
Klebsiella
sp. 10982 possesses a large IncA/C multidrug resistance plasmid encoding a novel FOX AmpC β-lactamase designated FOX-10. A novel variant of the LEN β-lactamase was also identified. Genome sequencing and bioinformatic analysis demonstrated that this isolate contains genes associated with nitrogen fixation, allantoin metabolism, and citrate fermentation. These three gene regions are typically present in either
Klebsiella pneumoniae
clinical isolates or
Klebsiella
nitrogen-fixing endophytes but usually not in the same organism. Phylogenomic analysis of
Klebsiella
sp. 10982 and sequenced
Klebsiella
genomes demonstrated that
Klebsiella
sp. 10982 is present on a branch that is located intermediate between the genomes of nitrogen-fixing endophytes and
K. pneumoniae
clinical isolates. Metabolic features identified in the genome of
Klebsiella
sp. 10982 distinguish this isolate from other
Klebsiella
clinical isolates. These features include the nitrogen fixation (
nif
) gene cluster, which is typically present in endophytic
Klebsiella
isolates and is absent from
Klebsiella
clinical isolates. Additionally, the
Klebsiella
sp. 10982 genome contains genes associated with allantoin metabolism, which have been detected primarily in
K. pneumoniae
isolates from liver abscesses. Comparative genomic analysis of
Klebsiella
sp. 10982 demonstrated that this organism has acquired genes conferring new metabolic strategies and novel antibiotic resistance alleles, both of which may enhance its ability to colonize the human body.
In Vivo
Efficacy of Ceftaroline Fosamil in a Methicillin-Resistant Panton-Valentine Leukocidin-Producing Staphylococcus aureus Rabbit Pneumonia Model
Authors: Croisier-Bertin Delphine , Hayez Davy , Da Silva Sonia , Labrousse Delphine , Biek Donald , Badiou Cedric , Dumitrescu Oana , Guerard Pascal , Charles Pierre-Emmanuel , Piroth Lionel , Lina Gerard , Vandenesch Francois , Chavanet Pascal
Published: January 2014

Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a cephalosporin with broad-spectrum
in vitro
activity against Gram-positive organisms, including methicillin-resistant
Staphylococcus aureus
(MRSA) and multidrug-resistant
Streptococcus pneumoniae
(MDRSP), and common Gram-negative pathogens. This study investigated the
in vivo
activity of ceftaroline fosamil compared with clindamycin, linezolid, and vancomycin in a severe pneumonia model due to MRSA-producing Panton-Valentine leukocidin (PVL). A USA300 PVL-positive clone was used to induce pneumonia in rabbits. Infected rabbits were randomly assigned to no treatment or simulated human-equivalent dosing with ceftaroline fosamil, clindamycin, linezolid, or vancomycin. Residual bacterial concentrations in the lungs and spleen were assessed after 48 h of treatment. PVL expression was measured using a specific enzyme-linked immunosorbent assay (ELISA). Ceftaroline, clindamycin, and linezolid considerably reduced mortality rates compared with the control, whereas vancomycin did not. Pulmonary and splenic bacterial titers and PVL concentrations were greatly reduced by ceftaroline, clindamycin, and linezolid. Ceftaroline, clindamycin, and linezolid were associated with reduced pulmonary tissue damage based on significantly lower macroscopic scores. Ceftaroline fosamil, clindamycin, and, to a lesser extent, linezolid were efficient in reducing bacterial titers in both the lungs and spleen and decreasing macroscopic scores and PVL production compared with the control.
Sphingolipid Biosynthetic Pathway Genes
FEN1
and
SUR4
Modulate Amphotericin B Resistance
Authors: Sharma Sushma , Alfatah   , Bari Vinay K. , Rawal Yashpal , Paul Sanjoy , Ganesan K.
Published: January 2014

Deletants of the sphingolipid biosynthetic pathway genes
FEN1
and
SUR4
of
Saccharomyces cerevisiae
, as well as deletants of their orthologs in
Candida albicans
, were found to be 2- to 5-fold-more sensitive to amphotericin B (AmB) than parent strains. The inhibition of sphingolipid biosynthesis in parent strains by myriocin sensitized them to AmB, which can be reversed by providing phytosphingosine, an intermediate in the sphingolipid pathway. These results indicate that sphingolipids modulate AmB resistance, with implications for mechanisms underlying AmB action and resistance.
In Vitro
Screening Test Using Leishmania Promastigotes Stably Expressing mCherry Protein
Authors: Vacchina Paola , Morales Miguel A.
Published: January 2014

Transgenic
Leishmania major
and
Leishmania donovani
axenic promastigotes constitutively expressing mCherry were used for
in vitro
antileishmanial drug screening. This method requires minimal sample manipulation and can be easily adapted to automatic drug tests, allowing primary high-throughput screenings without the need for expensive and sophisticated instruments.
Identification of a Key Lysine Residue in Heat Shock Protein 90 Required for Azole and Echinocandin Resistance in Aspergillus fumigatus
Authors: Lamoth Frédéric , Juvvadi Praveen R. , Soderblom Erik J. , Moseley M. Arthur , Asfaw Yohannes G. , Steinbach William J.
Published: January 2014

Heat shock protein 90 (Hsp90) is an essential chaperone involved in the fungal stress response that can be harnessed as a novel antifungal target for the treatment of invasive aspergillosis. We previously showed that genetic repression of Hsp90 reduced
Aspergillus fumigatus
virulence and potentiated the effect of the echinocandin caspofungin. In this study, we sought to identify sites of posttranslational modifications (phosphorylation or acetylation) that are important for Hsp90 function in
A. fumigatus
. Phosphopeptide enrichment and tandem mass spectrometry revealed phosphorylation of three residues in Hsp90 (S49, S288, and T681), but their mutation did not compromise Hsp90 function. Acetylation of lysine residues of Hsp90 was recovered after treatment with deacetylase inhibitors, and acetylation-mimetic mutations (K27A and K271A) resulted in reduced virulence in a murine model of invasive aspergillosis, supporting their role in Hsp90 function. A single deletion of lysine K27 or an acetylation-mimetic mutation (K27A) resulted in increased susceptibility to voriconazole and caspofungin. This effect was attenuated following a deacetylation-mimetic mutation (K27R), suggesting that this site is crucial and should be deacetylated for proper Hsp90 function in antifungal resistance pathways. In contrast to previous reports in
Candida albicans
, the lysine deacetylase inhibitor trichostatin A (TSA) was active alone against
A. fumigatus
and potentiated the effect of caspofungin against both the wild type and an echinocandin-resistant strain. Our results indicate that the Hsp90 K27 residue is required for azole and echinocandin resistance in
A. fumigatus
and that deacetylase inhibition may represent an adjunctive anti-
Aspergillus
strategy.
Mechanism of Resistance to an Antitubercular 2-Thiopyridine Derivative That Is Also Active against Burkholderia cenocepacia
Authors: Scoffone Viola C. , Spadaro Francesca , Udine Claudia , Makarov Vadim , Fondi Marco , Fani Renato , De Rossi Edda , Riccardi Giovanna , Buroni Silvia
Published: January 2014

The discovery of new compounds that are able to inhibit the growth of
Burkholderia cenocepacia
is of primary importance for cystic fibrosis patients. Here, the mechanism of resistance to a new pyridine derivative already shown to be effective against
Mycobacterium tuberculosis
and to have good activity toward
B. cenocepacia
was investigated. Increased expression of a resistance-nodulation-cell division (RND) efflux system was detected in the resistant mutants, thus confirming their important roles in
B. cenocepacia
antibiotic resistance.
Prior Exposure to Lamivudine Increases Entecavir Resistance Risk in Chronic Hepatitis B Patients without Detectable Lamivudine Resistance
Authors: Lee Jeong-Hoon , Cho Yuri , Lee Dong Hyeon , Lee Minjong , Yoo Jeong-ju , Choi Won-mook , Cho Young Youn , Lee Yun Bin , Yu Su Jong , Yoon Jung-Hwan , Lee Hyo-Suk , Kim Yoon Jun
Published: January 2014

The efficacy of entecavir (ETV) treatment in chronic hepatitis B (CHB) patients who were exposed to lamivudine (LAM) but had no detectable LAM resistance (LAM-R) is not well evaluated. In this study, we aimed to evaluate whether the probability of developing genotypic resistance to ETV in LAM-exposed patients with or without LAM-R is comparable to that in antiviral-naive patients. This retrospective cohort study included 500 consecutive patients with CHB who started ETV monotherapy at a single tertiary hospital in Korea. The patients were divided into three groups: nucleos(t)ide analogue (NA)-naive patients (group 1,
n
= 142), patients who were previously exposed to LAM and had no currently or previously detected LAM-R (group 2,
n
= 233), and patients with LAM-R when starting ETV (group 3,
n
= 125). The overall median ETV treatment duration was 48.7 months. The probabilities of virologic breakthrough were significantly increased not only in group 3 (hazard ratio [HR] = 14.4,
P
< 0.001) but also in group 2 (HR = 5.0,
P
< 0.001) compared to group 1. Genotypic ETV resistance (ETV-R) developed more frequently in group 2 (HR = 13.0,
P
= 0.013) as well as group 3 (HR = 43.9,
P
< 0.001) than in group 1: the probabilities of developing ETV-R in groups 1, 2, and 3 were <1.0%, 8.0%, and 28.2%, respectively, at month 48. The results of this study indicate that ETV-R occurred more frequently in LAM-exposed patients, even though they had no detectable LAM-R, than in NA-naive patients. Therefore, LAM-exposed CHB patients, regardless of the presence or absence of LAM-R, should be monitored more cautiously for the development of ETV-R during ETV monotherapy.
Complete Sequence of a KPC-Producing IncN Multidrug-Resistant Plasmid from an Epidemic Escherichia coli Sequence Type 131 Strain in China
Authors: Chen Liang , Hu Hongyan , Chavda Kalyan D. , Zhao Shulong , Liu Renkun , Liang Hui , Zhang Wei , Wang Xiumei , Jacobs Michael R. , Bonomo Robert A. , Kreiswirth Barry N.
Published: January 2014

We report here the nucleotide sequence of a novel
bla
KPC-2
-harboring incompatibility group N (IncN) plasmid, pECN580, from a multidrug-resistant
Escherichia coli
sequence type 131 (ST131) isolate recovered from Beijing, China. pECN580 harbors β-lactam resistance genes
bla
KPC-2
,
bla
CTX-M-3
, and
bla
TEM-1
; aminoglycoside acetyltransferase gene
aac
(
6
′)-
Ib-cr
; quinolone resistance gene
qnrS1
; rifampin resistance gene
arr-3
; and trimethoprim resistance gene
dfrA14
. The emergence of a
bla
KPC-2
-harboring multidrug-resistant plasmid in an epidemic
E. coli
ST131 clone poses a significant potential threat in community and hospital settings.
Dent's disease complicated by an acute Budd-Chiari syndrome
Authors: Platt Caroline , Jadresic Lyda , Dudley Jan , Hartley Jane L
Published: January 2014

We present the case of a young boy with Dent's disease, identified as having a mutation in the kidney-specific chloride-proton antitransporter CLCN5 during investigation for nephrotic-range proteinuria. He went on to develop growth hormone deficiency and was treated with recombinant growth hormone. He later presented acutely with hepatorenal failure and thrombotic occlusion of the middle and right hepatic veins consistent with a diagnosis of Budd-Chiari syndrome, which required a prolonged period of intensive care. The diagnosis of Dent's disease should be considered early in boys with nephrotic-range proteinuria in the absence of clinical oedema and hypoalbuminaemia to allow for the timely introduction of strategies, such as a high-citrate diet, to preserve renal function. The measurement of urinary β-2 microglobulin has been shown by this case to be a more reliable and specific marker of tubular dysfunction than the urinary retinol-binding protein.
Herbal medicine (Gan Mai Da Zao decoction) for depression: a systematic review protocol
Authors: Jun Ji Hee , Lee Ju Ah , Choi Tae-Young , Yun Kyung-Jin , Lim Hyun-Ja , Lee Myeong Soo
Published: January 2014

Introduction

The aim of this systematic review is to analyse trial data on the effectiveness of a herbal medicine (Gan Mai Da Zao (GMDZ) decoction) in treating depression.

Methods and analysis

12 databases will be searched from their inception: PubMed, EMBASE, AMED, the Cochrane Library, five Korean medical databases (KoreaMed, DBpia, OASIS, the Research Information Service System (RISS) and the Korean Studies Information Service System (KISS)) and three Chinese medical databases (China National Knowledge Infrastructure (CNKI), the Wanfang Database and the Chinese Scientific Journals Database (VIP)). Randomised clinical trials (RCTs) or quasi-RCTs using a GMDZ decoction for any type of depression will be considered. The selection of the studies, data abstraction and validations will be performed independently by two researchers.

Dissemination

The findings will be disseminated to appropriate audiences via peer-reviewed publication and conference presentations.

Trial registration number

PROSPERO 2013:CRD42013005100.
Intravenous paracetamol versus dexketoprofen in acute migraine attack in the emergency department: a randomised clinical trial
Authors: Turkcuer Ibrahim , Serinken Mustafa , Eken Cenker , Yilmaz Atakan , Akdag Ömer , Uyanık Emrah , Kiray Cihan , Elicabuk Hayri
Published: January 2014

Objective

Migraine is a common form of headache that is a major burden for patients who often seek emergency care. The goal of this study was to compare the effectiveness of intravenous non-steroidal anti-inflammatory medication (dexketoprofen) with paracetamol (acetaminophen) in the treatment of an acute migraine attack.

Materials and methods

This prospective, randomised, double blind, controlled study was conducted in a tertiary care emergency unit. Study patients were randomised into two groups to receive either 50 mg of dexketoprofen trometamol or 1000 mg of paracetamol intravenously by rapid infusion in 150 mL of normal saline. Pain reduction was measured at baseline, and after 15 and 30 min, using a Visual Analogue Scale (VAS)) as the primary outcome. VAS is a measurement tool ranging from 0 (no pain) to 100 mm (worst pain).

Results

200 patients were included in the final analysis. Mean (SD) age of the study subjects was 30.1±11 years and 81% (n=162) were women. Median reduction in VAS score at 30 min was 56 (IQR 30–78.5) for the paracetamol group and 55 (IQR 34–75) for the dexketoprofen group, with a difference of 1 mm (95% CI −7 to 10) between the two groups.

Conclusions

Intravenous paracetamol and dexketoprofen appear to produce equivalent pain relief for migraine in the emergency department.

ClinicalTrials.gov No

NCT01730326.
Clinicians’ views on low-lying intrauterine devices or systems
Authors: Golightly Ellen , Gebbie Ailsa E
Published: January 2014

Background

There is a lack of consensus and very little published guidance on the management of a low-lying or malpositioned intrauterine contraceptive device (IUD) or system (IUS).

Methods and results

A short e-mail questionnaire sent to senior medical staff working in contraceptive services confirmed the variation in views and management of this clinical area. Almost all respondents would replace an IUD/IUS lying either totally or partially in the cervical canal. The nearer the device was to the fundus the more likely respondents were to leave itin situand there was less concern if the device was an IUS, presumably in view of the hormonal action. In the presence of abnormal bleeding or pain, most respondents would look for other causes rather than assume that the low-lying device was to blame. Respondents expressed uncertainty as to whether low-lying devices were more likely to fail or not and around half the respondents felt that low-lying devices could migrate upwards within the cavity.

Conclusion

This survey highlighted the need for accurate evidence-based guidance to assist in this area of clinical contraceptive practice.