bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of the geographical scale of adaptive phenological variation and its underlying genetics in Arabidopsis thaliana
Authors: Brachi Benjamin , Villoutreix Romain , Faure Nathalie , Hautekèete Nina , Piquot Yves , Pauwels Maxime , Roby Dominique , Cuguen Joël , Bergelson Joy , Roux Fabrice 
Published: July 2013

AbstractDespite the increasing number of genomic tools, identifying the genetics underlying adaptive complex traits remains challenging in the model species Arabidopsis thaliana. This is due, at least in part, to the lack of data on the geographical scale of adaptive phenotypic variation. The aims of this study were (i) to tease apart the historical roles of adaptive and nonselective processes in shaping phenological variation in A. thaliana in France and (ii) to gain insights into the spatial scale of adaptive variation by identifying the putative selective agents responsible for this selection. Forty‐nine natural stands from four climatically contrasted French regions were characterized (i) phenologically for six traits, (ii) genetically using 135 SNP markers and (iii) ecologically for 42 variables. Up to 63% of phenological variation could be explained by neutral genetic diversity. The remaining phenological variation displayed stronger associations with ecological variation within regions than among regions, suggesting the importance of local selective agents in shaping adaptive phenological variation. Although climatic conditions have often been suggested as the main selective agents acting on phenology in A. thaliana, both edaphic conditions and interspecific competition appear to be strong selective agents in some regions. In a first attempt to identify the genetics of phenological variation at different geographical scales, we phenotyped worldwide accessions and local polymorphic populations from the French RegMap in a genome‐wide association (GWA) mapping study. The genomic regions associated with phenological variation depended upon the geographical scale considered, stressing the need to account for the scale of adaptive phenotypic variation when choosing accession panels for GWAS.
Vertical nontransovarial transmission of Bartonella in fleas
Authors: Morick Danny , Krasnov Boris R. , Khokhlova Irina S. , Gutiérrez Ricardo , Gottlieb Yuval , Harrus Shimon 
Published: July 2013

AbstractPathogens use diverse pathways to infect host populations by vertical and/or horizontal routes. Horizontal transmission of bacteria belonging to the Bartonella genus via haematophagous vectors is well known. Vertical transmission of Bartonella species was also suggested to occur but its routes remain to be unveiled. In a previous study, we showed the absence of transovarial transmission of Bartonella species OE 1‐1 in Xenopsylla ramesis fleas, and that fleas feeding on Bartonella‐positive jirds produced Bartonella‐positive gut voids. This current study aimed to investigate whether vertical nontransovarial transmission of Bartonella occurs in fleas. For this aim, the X. ramesis–Bartonella sp. OE 1‐1 model was used. Four groups of fleas including Bartonella‐positive and Bartonella‐negative female fleas and larval offspring had access to either Bartonella‐negative or Bartonella‐positive gut voids and faeces. Sixteen per cent of flea offspring that had access to Bartonella‐positive faeces and gut voids became Bartonella positive. Our findings demonstrate that Bartonella‐positive flea faeces and gut voids are proper infection sources for flea larvae and indicate that vertical nontransovarial transmission of bartonellae occurs in fleas. This information broadens our understanding of Bartonella transmission routes in flea vectors and enlightens pathways of bartonellae transmission and maintenance in flea populations in nature.
TNFα Secretion of Monocytes Exposed to Pulsed Radiofrequency Treatment: A Possible Working Mechanism of PRF Chronic Pain Management
Authors: Maretto Fabio , Vennik Marco , Albers Kim I. , van Duijn Bert 
Published: July 2013

AbstractPulsed radiofrequency treatment (PRF) is a promising new technique increasingly used in treatment of chronic pain. The molecular working mechanism of PRF is not exactly known and is currently being investigated. This study investigates a possible role of PRF‐induced modulation of TNFα secretion by differentiated monocytes in chronic pain management. The results show no significant PRF‐induced change in TNFα secretion of lipopolysaccharides (LPS)‐stimulated monocytes. However, PRF does significantly increase TNFα secretion of differentiated monocytes that have not been stimulated with LPS. This may indicate a possible role of PRF treatment in increasing TNFα production of nonstimulated monocytes. More research is needed to determine whether this is truly a part of the working mechanism of PRF in chronic pain management and which other factors are involved.
A multidisciplinary approach to understanding carbonate deposition under tectonically controlled hydrothermal circulation: A case study from a recent travertine mound in the Euganean hydrothermal system, northern Italy
Authors: Pola Marco , Gandin Anna , Tuccimei Paola , Soligo Michele , Deiana Rita , Fabbri Paolo , Zampieri Dario 
Published: July 2013

AbstractA multidisciplinary study was carried out on an Upper Pleistocene travertine mound (Montirone Hill; Abano Terme, south of Padova, Veneto, Italy) with the aim of developing a comprehensive understanding of the processes interacting in structurally controlled thermal springs and the consequent deposition of thermal limestones. The sedimentology, geochemistry, structural characteristics and hydrogeology of the mound, which is associated with the Euganean geothermal field and the related complex structural framework of the Schio‐Vicenza fault system, were investigated. A palaeo‐environmental model of the deposit has been reconstructed clarifying the connection between the travertine deposition and the regional structural setting. Calcium‐rich thermal waters rose from spring orifices (estimated temperature from 54°C to 61°C based on geochemical calculations) and produced a mound made of coalescent shield‐like bodies. The dominant lime‐mudstone facies resulted from the accumulation of lime mud at the bottom of shallow crater‐like basins located on top of stacked cones. Soft sediment deformations affecting the lime mud sediment were most probably produced by the recurrent uprising of gas bubbles. The overlying crystalline crusts were deposited on the flanks of the mound by waters overflowing from the vents with laminar flux. A deep hydrothermal circuit with a long period of water–rock interaction is supported by geochemical analyses. Furthermore, a local extensional regime, enhancing the migration of thermal fluids to the surface, is inferred based on the results of the structural analysis carried out on the fault/fracture mesh that affects the mound. These results corroborate the well‐established relation among travertine deposits, hydrothermal systems and fault systems, and substantiate the structurally controlled conceptual model of the Euganean hydrothermal system, suggesting that both the thermal and the fault systems were active at least since 34 ka.
Successful medical treatment for globe penetration following tooth extraction in a dog
Authors: Guerreiro Cleo E. , Appelboam Helen , Lowe Robert C. 
Published: July 2013

AbstractA five‐year‐old entire male Tibetan Terrier was referred for left‐sided periorbital swelling and blepharospasm 4 days following ipsilateral maxillary tooth extraction. Examination of the left eye revealed mild exophthalmos, pain on retropulsion, and absent menace response and pupillary light reflexes. Examination of the posterior segment was not possible owing to the anterior segment pathology. Differential diagnoses considered were iatrogenic globe penetration and peribulbar abscess/cellulitis. Ocular ultrasound was consistent with a penetrating wound to the globe. Treatment with systemic prednisolone and marbofloxacin, and topical atropine sulfate 1%, prednisolone acetate, and brinzolamide was started. Marked clinical improvement allowed visual confirmation of the perforation. Oral prednisolone was tapered over the following 10 weeks. At final re‐examination (10 months), the patient was visual, and fundic examination revealed an additional chorioretinal scar, most likely an exit wound that was obscured by vitreal debris on initial examinations. Neither scar was associated with retinal detachment. To the authors' knowledge, this is the first reported case of successful medical management of iatrogenic globe penetration following exodontic procedures.
Spinal TNFα is necessary for inactivity‐induced phrenic motor facilitation
Authors: Broytman Oleg , Baertsch Nathan A. , Baker‐Herman Tracy L. 
Published: July 2013

Key points
A central neural apnoea in the absence of hypoxia elicits a form of respiratory plasticity known as inactivity‐induced phrenic motor facilitation (iPMF), a rebound increase in phrenic burst amplitude when central respiratory neural activity is restored.
iPMF requires spinal atypical protein kinase C (aPKC) activity in spinal segments encompassing the phrenic motor nucleus.
Here, we report novel findings that tumour necrosis factor‐α (TNFα) signalling in or near the phrenic motor pool is necessary and sufficient for iPMF as: (1) spinal TNFα inhibition inhibits iPMF; and (2) spinal TNFα elicits long‐lasting increases in phrenic burst amplitude via an aPKC‐dependent mechanism.
These data are consistent with the hypothesis that local mechanisms operating within or near the phrenic motor pool sense and respond to reduced respiratory neural activity, and suggest that TNFα‐induced activation of aPKC near phrenic motor neurons forms part of the core cellular pathway giving rise to iPMF.
Abstract  A prolonged reduction in central neural respiratory activity elicits a form of plasticity known as inactivity‐induced phrenic motor facilitation (iPMF), a ‘rebound’ increase in phrenic burst amplitude apparent once respiratory neural activity is restored. iPMF requires atypical protein kinase C (aPKC) activity within spinal segments containing the phrenic motor nucleus to stabilize an early transient increase in phrenic burst amplitude and to form long‐lasting iPMF following reduced respiratory neural activity. Upstream signal(s) leading to spinal aPKC activation are unknown. We tested the hypothesis that spinal tumour necrosis factor‐α (TNFα) is necessary for iPMF via an aPKC‐dependent mechanism. Anaesthetized, ventilated rats were exposed to a 30 min neural apnoea; upon resumption of respiratory neural activity, a prolonged increase in phrenic burst amplitude (42 ± 9% baseline; P < 0.05) was apparent, indicating long‐lasting iPMF. Pretreatment with recombinant human soluble TNF receptor 1 (sTNFR1) in the intrathecal space at the level of the phrenic motor nucleus prior to neural apnoea blocked long‐lasting iPMF (2 ± 8% baseline; P > 0.05). Intrathecal TNFα without neural apnoea was sufficient to elicit long‐lasting phrenic motor facilitation (pMF; 62 ± 7% baseline; P < 0.05). Similar to iPMF, TNFα‐induced pMF required spinal aPKC activity, as intrathecal delivery of a ζ‐pseudosubstrate inhibitory peptide (PKCζ‐PS) 35 min following intrathecal TNFα arrested TNFα‐induced pMF (28 ± 8% baseline; P < 0.05). These data demonstrate that: (1) spinal TNFα is necessary for iPMF; and (2) spinal TNFα is sufficient to elicit pMF via a similar aPKC‐dependent mechanism. These data are consistent with the hypothesis that reduced respiratory neural activity elicits iPMF via a TNFα‐dependent increase in spinal aPKC activity.
Mechanisms of retroaxonal barrage firing in hippocampal interneurons
Authors: Sheffield Mark E. J. , Edgerton Gabrielle B. , Heuermann Robert J. , Deemyad Tara , Mensh Brett D. , Spruston Nelson 
Published: July 2013

Key points
Persistent firing can be triggered in a population of inhibitory interneurons found in the hippocampus and neocortex. Repeated stimulation eventually triggers an autonomous barrage of spikes that is generated and maintained in the axon, followed by antidromic propagation to the soma.
This barrage of spikes is generated and maintained in the axon, followed by antidromic propagation to the soma. The mechanisms underlying this ‘retroaxonal barrage firing’ are unknown.
We find that retroaxonal barrage firing is Ca2+ dependent, is inhibited by the L‐type Ca2+ channel blockers cadmium, nifedipine and verapamil, and does not require synaptic transmission. Loading the stimulated interneuron with BAPTA did not block barrage firing, suggesting that the required Ca2+ entry may occur in other cells.
Retroaxonal barrage firing was observed in mice lacking the Cx36 isoform (most common neuronal isoform), indicating that this particular isoform is not required.
Abstract  We recently described a new form of neural integration and firing in a subset of interneurons, in which evoking hundreds of action potentials over tens of seconds to minutes produces a sudden barrage of action potentials lasting about a minute beyond the inciting stimulation. During this persistent firing, action potentials are generated in the distal axon and propagate retrogradely to the soma. To distinguish this from other forms of persistent firing, we refer to it here as ‘retroaxonal barrage firing’, or ‘barrage firing’ for short. Its induction is blocked by chemical inhibitors of gap junctions and curiously, stimulation of one interneuron in some cases triggers barrage firing in a nearby, unstimulated interneuron. Beyond these clues, the mechanisms of barrage firing are unknown. Here we report new results related to these mechanisms. Induction of barrage firing was blocked by lowering extracellular calcium, as long as normal action potential threshold was maintained, and it was inhibited by blocking L‐type voltage‐gated calcium channels. Despite its calcium dependence, barrage firing was not prevented by inhibiting chemical synaptic transmission. Furthermore, loading the stimulated/recorded interneuron with BAPTA did not block barrage firing, suggesting that the required calcium entry occurs in other cells. Finally, barrage firing was normal in mice with deletion of the primary gene for neuronal gap junctions (connexin36), suggesting that non‐neuronal gap junctions may be involved. Together, these findings suggest that barrage firing is probably triggered by a multicellular mechanism involving calcium signalling and gap junctions, but operating independently of chemical synaptic transmission.
How LeuT shapes our understanding of the mechanisms of sodium‐coupled neurotransmitter transporters
Authors: Penmatsa Aravind , Gouaux Eric 
Published: July 2013

AbstractNeurotransmitter transporters are ion‐coupled symporters that drive the uptake of neurotransmitters from neural synapses. In the past decade, the structure of a bacterial amino acid transporter, leucine transporter (LeuT), has given valuable insights into the understanding of architecture and mechanism of mammalian neurotransmitter transporters. Different conformations of LeuT, including a substrate‐free state, inward‐open state, and competitive and non‐competitive inhibitor‐bound states, have revealed a mechanistic framework for the transport and transport inhibition of neurotransmitters. The current review integrates our understanding of the mechanistic and pharmacological properties of eukaryotic neurotransmitter transporters obtained through structural snapshots of LeuT.
Identification of Extended-Spectrum-β-Lactamase-Positive Klebsiella pneumoniae Urinary Tract Isolates Harboring KPC and CTX-M β-Lactamases in Nonhospitalized Patients
Authors: Kopacz Joanna , Mariano Noriel , Colon-Urban Rita , Sychangco Paul , Wehbeh Wehbeh , Segal-Maurer Sorana , Urban Carl 
Published: July 2013

ABSTRACT

Forty-seven extended-spectrum-β-lactamase-positive
Klebsiella pneumoniae
urinary tract isolates from nonhospitalized patients were identified, and 79% harbored KPC and/or CTX-M β-lactamases. Approximately 90% of the isolates were resistant to trimethoprim-sulfamethoxazole and levofloxacin, and 40% were resistant to a carbapenem, while 92% were susceptible to polymyxin B, 87% were susceptible to tigecycline, and 79% were susceptible to fosfomycin. Increased use of broader-spectrum antibiotics may help to prevent their dissemination and reduce the risk of progression to invasive disease.
Cyclic AMP Effectors in African Trypanosomes Revealed by Genome-Scale RNA Interference Library Screening for Resistance to the Phosphodiesterase Inhibitor CpdA
Authors: Gould Matthew K. , Bachmaier Sabine , Ali Juma A. M. , Alsford Sam , Tagoe Daniel N. A. , Munday Jane C. , Schnaufer Achim C. , Horn David , Boshart Michael , de Koning Harry P. 
Published: July 2013

ABSTRACT

One of the most promising new targets for trypanocidal drugs to emerge in recent years is the cyclic AMP (cAMP) phosphodiesterase (PDE) activity encoded by
TbrPDEB1
and
TbrPDEB2
. These genes were genetically confirmed as essential, and a high-affinity inhibitor, CpdA, displays potent antitrypanosomal activity. To identify effectors of the elevated cAMP levels resulting from CpdA action and, consequently, potential sites for adaptations giving resistance to PDE inhibitors, resistance to the drug was induced. Selection of mutagenized trypanosomes resulted in resistance to CpdA as well as cross-resistance to membrane-permeable cAMP analogues but not to currently used trypanocidal drugs. Resistance was not due to changes in cAMP levels or in
PDEB
genes. A second approach, a genome-wide RNA interference (RNAi) library screen, returned four genes giving resistance to CpdA upon knockdown. Validation by independent RNAi strategies confirmed resistance to CpdA and suggested a role for the identified
cA
MP
R
esponse
P
roteins (CARPs) in cAMP action. CARP1 is unique to kinetoplastid parasites and has predicted cyclic nucleotide binding-like domains, and RNAi repression resulted in >100-fold resistance. CARP2 and CARP4 are hypothetical conserved proteins associated with the eukaryotic flagellar proteome or with flagellar function, with an orthologue of CARP4 implicated in human disease. CARP3 is a hypothetical protein, unique to
Trypanosoma
. CARP1 to CARP4 likely represent components of a novel cAMP signaling pathway in the parasite. As cAMP metabolism is validated as a drug target in
Trypanosoma brucei
, cAMP effectors highly divergent from the mammalian host, such as
CARP1
, lend themselves to further pharmacological development.
Combination of Pantothenamides with Vanin Inhibitors as a Novel Antibiotic Strategy against Gram-Positive Bacteria
Authors: Jansen Patrick A. M. , Hermkens Pedro H. H. , Zeeuwen Patrick L. J. M. , Botman Peter N. M. , Blaauw Richard H. , Burghout Peter , van Galen Peter M. , Mouton Johan W. , Rutjes Floris P. J. T. , Schalkwijk Joost 
Published: July 2013

ABSTRACT

The emergence of resistance against current antibiotics calls for the development of new compounds to treat infectious diseases. Synthetic pantothenamides are pantothenate analogs that possess broad-spectrum antibacterial activity
in vitro
in minimal media. Pantothenamides were shown to be substrates of the bacterial coenzyme A (CoA) biosynthetic pathway, causing cellular CoA depletion and interference with fatty acid synthesis. In spite of their potential use and selectivity for bacterial metabolic routes, these compounds have never made it to the clinic. In the present study, we show that pantothenamides are not active as antibiotics in the presence of serum, and we found that they were hydrolyzed by ubiquitous pantetheinases of the vanin family. To address this further, we synthesized a series of pantetheinase inhibitors based on a pantothenate scaffold that inhibited serum pantetheinase activity in the nanomolar range. Mass spectrometric analysis showed that addition of these pantetheinase inhibitors prevented hydrolysis of pantothenamides by serum. We found that combinations of these novel pantetheinase inhibitors and prototypic pantothenamides like N5-Pan and N7-Pan exerted antimicrobial activity
in vitro
, particularly against Gram-positive bacteria (
Staphylococcus aureus
,
Staphylococcus epidermidis
,
Streptococcus pneumoniae
, and
Streptococcus pyogenes
) even in the presence of serum. These results indicate that pantothenamides, when protected against degradation by host pantetheinases, are potentially useful antimicrobial agents.
Synchrotron X-Ray Fluorescence Microscopy of Gallium in Bladder Tissue following Gallium Maltolate Administration during Urinary Tract Infection
Authors: Ball Katherine R. , Sampieri Francesca , Chirino Manuel , Hamilton Don L. , Blyth Robert I. R. , Sham Tsun-Kong , Dowling Patricia M. , Thompson Julie 
Published: July 2013

ABSTRACT

A mouse model of cystitis caused by uropathogenic
Escherichia coli
was used to study the distribution of gallium in bladder tissue following oral administration of gallium maltolate during urinary tract infection. The median concentration of gallium in homogenized bladder tissue from infected mice was 1.93 μg/g after daily administration of gallium maltolate for 5 days. Synchrotron X-ray fluorescence imaging and X-ray absorption spectroscopy of bladder sections confirmed that gallium arrived at the transitional epithelium, a potential site of uropathogenic
E. coli
infection. Gallium and iron were similarly but not identically distributed in the tissues, suggesting that at least some distribution mechanisms are not common between the two elements. The results of this study indicate that gallium maltolate may be a suitable candidate for further development as a novel antimicrobial therapy for urinary tract infections caused by uropathogenic
E. coli
.
Susceptibility to Alternative Oral Antimicrobial Agents in Relation to Sequence Type ST131 Status and Coresistance Phenotype among Recent Escherichia coli Isolates from U.S. Veterans
Authors: Johnson James R. , Drawz Sarah M. , Porter Stephen , Kuskowski Michael A. 
Published: July 2013

ABSTRACT

The rising prevalence of resistance to first-line antimicrobial agents in
Escherichia coli
, which has paralleled the emergence of
E. coli
sequence type ST131, has created a need for alternative oral options for use in treating outpatients with infections such as cystitis and chronic prostatitis. Accordingly, we determined susceptibility to six alternative oral agents (azithromycin, chloramphenicol, doxycycline, fosfomycin, minocycline, and rifampin) by Etest or disk diffusion for 120 recently obtained
E. coli
clinical isolates from Veterans Affairs Medical Centers across the United States. Isolates were randomly selected in three subgroups of 40 isolates each based on coresistance to fluoroquinolones with and without extended-spectrum cephalosporins (ESCs). Results were stratified according to trimethoprim-sulfamethoxazole (TMP-SMZ) phenotype. Overall, the prevalence of susceptible (or susceptible plus intermediate) isolates varied by agent, with rifampin being lowest (0%), fosfomycin highest (98 to 99%), and others in the mid-range (37 to 88%). Substantial proportions of isolates (15 to 27%) yielded intermediate results for azithromycin, chloramphenicol, doxycycline, and minocycline. Among isolates resistant (versus susceptible) to fluoroquinolones with or without ESCs, susceptibility to the above four agents declined significantly among non-ST131 isolates but not ST131 isolates. In contrast, in the presence of resistance to TMP-SMZ, susceptibility to azithromycin, doxycycline, and minocycline was significantly reduced among both ST131 and non-ST131 isolates. These findings identify potential alternative oral agents for use with
E. coli
isolates resistant to fluoroquinolones, ESCs, and/or TMP-SMZ and suggest that determination of ST131 status could help guide initial antimicrobial selection, pending susceptibility results.