bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ambulatory arterial stiffness index in children after kidney transplantation
Authors: Dégi Arianna , Kerti Andrea , Cseprekál Orsolya , Kis Éva , Sallay Péter , Szabó Attila J. , Reusz George S. 
Published: July 2013

AbstractGiven the increase in CV morbidity after RTx and the scarcity of CV events in pediatrics, surrogate markers should be assessed to characterize CV damage in this population. AASI is a marker of arterial stiffness in adults, predicting cardio‐ and cerebrovascular morbidity. Our aim was to assess the determinants of AASI in RTx children (n = 54, 15.5 ± 3.5 yr) and to examine its relationship to central PWV. AASI was calculated from 24 h ABPM. PWV was determined by applanation tonometry, body composition by multifrequency bioimpedance measurement. The dipping state, volume overload, and time on dialysis were the main predictors of AASI (p < 0.05). Children with established HT (n = 34) had increased AASI, extracellular body water, and BNP (p < 0.05). In contrast to AASI, PWV did not differ between HT and normotensive RTx patient groups. There was no correlation between AASI and PWV. PWV was increased in children who spent more than one yr on dialysis prior to RTx. In conclusion, increased AASI in HT RTx children better characterizes the actual volume‐ and pressure‐dependent arterial rigidity rather than long‐term morphological changes in large arteries as reflected by PWV.
Oral findings and dental treatment in a patient with Dandy–Walker syndrome: a case report
Authors: Kusumoto Yasuka , Shinozuka Osamu 
Published: July 2013

ABSTRACTDandy–Walker syndrome (DWS) is congenital disease characterized by hypoplasia of the cerebellum, the formation of cysts that communicate with the fourth ventricle of the posterior cranial fossa, and hydrocephalus. In addition to various other complications, cleft lip/palate, facial retrognathia, a high‐arched palate, and maldentition occur at an increased frequency in patients with DWS. However, few studies have reported the dental manifestations of DWS. Herein, we report the clinical manifestations, oral findings, and dental management of a DWS patient who was treated under general anesthesia. Poor oral hygiene, gingivitis, and several congenital dental abnormalities (e.g., generalized microdontia, conical tooth, transposition, and congenitally missing teeth) were observed. This report is the first to describe the oral findings and dental treatment of DWS. Our findings emphasize the importance of a multidisciplinary approach in the diagnosis and treatment of DWS.
Serum thymidine kinase 1 and C‐reactive protein as biomarkers for screening clinically healthy dogs for occult disease
Authors: Selting K. A. , Sharp C. R. , Ringold R. , Knouse J. 
Published: July 2013

AbstractThymidine kinase (TK1) is a biomarker that correlates well with diagnosis and prognosis in certain canine cancers. Canine C‐reactive protein (cCRP) is a widely accepted marker of inflammation correlated with increased risk and severity of various diseases. We evaluated serum TK1 and cCRP concentrations in apparently healthy dogs (n = 360). All dogs were followed up for a minimum of 6 months by health questionnaire. All dogs with cancer were identified using a proprietary dual‐biomarker algorithm [termed Neoplasia Index (NI)]. Specificity of positive NI is 0.91 and high positive is 0.98. All‐cause mortality was 20% in dogs with elevated cCRP and 3% in dogs with low cCRP. The performance of serum TK1 and cCRP as tools for screening for occult cancer is improved when evaluated together. Serum TK1 and cCRP (unified in the NI) are useful in the screening of occult canine cancer. cCRP is useful in screening for other serious diseases.
Hyperthermia does not alter the increase in cerebral perfusion during cognitive activation
Authors: Schlader Zachary J. , Lucas Rebekah A. I. , Pearson James , Crandall Craig G. 
Published: July 2013

New Findings
What is the central question of this study?Decreases in baseline cerebral perfusion impair the capacity to increase cerebral perfusion during cognitive activation. Hyperthermia reduces baseline cerebral perfusion, but it remains unknown whether hyperthermia also impairs the increase in cerebral perfusion during the execution of a cognitive task.
What is the main finding and its importance?This study shows that hyperthermia does not alter the increase in cerebral perfusion during a cognitive task. These findings have implications for individuals who are frequently exposed to heat stress in concert with a cognitive challenge.
This study tested the hypothesis that hyperthermia attenuates the increase in cerebral perfusion during cognitive activation. Mean middle cerebral artery blood velocity (MCAVmean) served as an index of cerebral perfusion, while the nBack test (a test of working memory) was the cognitive task. Hyperthermia was characterized by elevations (P < 0.001) in skin (by 5.0 ± 0.8°C) and intestinal temperatures (by 1.3 ± 0.1°C) and reductions (P < 0.020) in mean arterial pressure (by 11 ± 10 mmHg), end‐tidal CO2 tension (by 3 ± 6 mmHg) and MCAVmean (by 10 ± 9 cm s−1). Hyperthermia had no influence on nBack test performance (mean difference from normothermia to hyperthermia, −1 ± 11%; P= 0.276) or, counter to the hypothesis, the increase in MCAVmean during nBack testing (mean difference from normothermia to hyperthermia: 0 ± 16 cm s−1; P= 0.608). These findings indicate that the capacity to increase cerebral perfusion during cognitive activation is unaffected by hyperthermia.
Acute inhibition of diacylglycerol lipase blocks endocannabinoid‐mediated retrograde signalling: evidence for on‐demand biosynthesis of 2‐arachidonoylglycerol
Authors: Hashimotodani Yuki , Ohno‐Shosaku Takako , Tanimura Asami , Kita Yoshihiro , Sano Yoshikazu , Shimizu Takao , Di Marzo Vincenzo , Kano Masanobu 
Published: July 2013

Key points
2‐Arachidonoylglycerol (2‐AG), one of the best‐characterized retrograde messengers at central synapses, has been thought to be produced ‘on demand’ through a diacylglycerol lipase α (DGLα)‐dependent pathway upon activation of postsynaptic neurons (on‐demand synthesis hypothesis).
However, recent studies propose an alternative hypothesis that 2‐AG is pre‐synthesized by DGLα, stored in neurons, and released from such ‘pre‐formed pools’ without the participation of DGLα (pre‐formed pool hypothesis).
To test these hypotheses, we examined the effects of acute pharmacological inhibition of DGL by a novel potent DGL inhibitor, OMDM‐188, on retrograde 2‐AG signalling.
We found that 2‐AG‐mediated retrograde signalling was blocked after 1 h treatment with OMDM‐188 in acute slices from the hippocampus, striatum and cerebellum, and was blocked several minutes after OMDM‐188 application in cultured hippocampal neurons.
These results fit well with the on‐demand synthesis hypothesis, rather than the pre‐formed pool hypothesis.
Abstract  The endocannabinoid (eCB) 2‐arachidonoylglycerol (2‐AG) produced by diacylglycerol lipase α (DGLα) is one of the best‐characterized retrograde messengers at central synapses. It has been thought that 2‐AG is produced ‘on demand’ upon activation of postsynaptic neurons. However, recent studies propose that 2‐AG is pre‐synthesized by DGLα and stored in neurons, and that 2‐AG is released from such ‘pre‐formed pools’ without the participation of DGLα. To address whether the 2‐AG source for retrograde signalling is the on‐demand biosynthesis by DGLα or the mobilization from pre‐formed pools, we examined the effects of acute pharmacological inhibition of DGL by a novel potent DGL inhibitor, OMDM‐188, on retrograde eCB signalling triggered by Ca2+ elevation, Gq/11 protein‐coupled receptor activation or synergy of these two stimuli in postsynaptic neurons. We found that pretreatment for 1 h with OMDM‐188 effectively blocked depolarization‐induced suppression of inhibition (DSI), a purely Ca2+‐dependent form of eCB signalling, in slices from the hippocampus, striatum and cerebellum. We also found that at parallel fibre–Purkinje cell synapses in the cerebellum OMDM‐188 abolished synaptically induced retrograde eCB signalling, which is known to be caused by the synergy of postsynaptic Ca2+ elevation and group I metabotropic glutamate receptor (I‐mGluR) activation. Moreover, brief OMDM‐188 treatments for several minutes were sufficient to suppress both DSI and the I‐mGluR‐induced retrograde eCB signalling in cultured hippocampal neurons. These results are consistent with the hypothesis that 2‐AG for synaptic retrograde signalling is supplied as a result of on‐demand biosynthesis by DGLα rather than mobilization from presumptive pre‐formed pools.
Ca2+ and cAMP cross‐talk in mitochondria
Authors: Di Benedetto Giulietta , Pendin Diana , Greotti Elisa , Pizzo Paola , Pozzan Tullio 
Published: July 2013

AbstractWhile mitochondrial Ca2+ homeostasis has been studied for several decades and many of the functional roles of Ca2+ accumulation within the matrix have been at least partially clarified, the possibility of modulation of the organelle functions by cAMP remains largely unknown. In this contribution we briefly summarize the key aspects of Ca2+ and cAMP signalling pathways in mitochondria. In particular, we focus on recent findings concerning the discovery of an autonomous cAMP toolkit within the mitochondrial matrix, its crossroad with mitochondrial Ca2+ signalling and its role in controlling ATP synthesis. The discovery of a cAMP signalling, and the demonstration of a cross‐talk between cAMP and Ca2+ inside mitochondria, open the way to a re‐evaluation of these organelles as integrators of multiple second messengers. A description of the main methods presently available to measure Ca2+ and cAMP in mitochondria of living cells with genetically encoded probes is also presented.
Chimeric Cyanovirin-MPER Recombinantly Engineered Proteins Cause Cell-Free Virolysis of HIV-1
Authors: Contarino Mark , Bastian Arangassery R. , Kalyana Sundaram Ramalingam Venkat , McFadden Karyn , Duffy Caitlin , Gangupomu Vamshi , Baker Michelle , Abrams Cameron , Chaiken Irwin 
Published: July 2013

ABSTRACT

Human immunodeficiency virus (HIV) is the primary etiologic agent responsible for the AIDS pandemic. In this work, we used a chimeric recombinant protein strategy to test the possibility of irreversibly destroying the HIV-1 virion using an agent that simultaneously binds the Env protein and viral membrane. We constructed a fusion of the lectin cyanovirin-N (CVN) and the gp41 membrane-proximal external region (MPER) peptide with a variable-length (Gly
4
Ser)

x

linker (where
x
is 4 or 8) between the C terminus of the former and N terminus of the latter. The His-tagged recombinant proteins, expressed in BL21(DE3)pLysS cells and purified by immobilized metal affinity chromatography followed by gel filtration, were found to display a nanomolar efficacy in blocking BaL-pseudotyped HIV-1 infection of HOS.T4.R5 cells. This antiviral activity was HIV-1 specific, since it did not inhibit cell infection by vesicular stomatitis virus (VSV) or amphotropic-murine leukemia virus. Importantly, the chimeric proteins were found to release intraviral p24 protein from both BaL-pseudotyped HIV-1 and fully infectious BaL HIV-1 in a dose-dependent manner in the absence of host cells. The addition of either MPER or CVN was found to outcompete this virolytic effect, indicating that both components of the chimera are required for virolysis. The finding that engaging the Env protein spike and membrane using a chimeric ligand can destabilize the virus and lead to inactivation opens up a means to investigate virus particle metastability and to evaluate this approach for inactivation at the earliest stages of exposure to virus and before host cell encounter.
The
R
Enantiomer of the Antitubercular Drug PA-824 as a Potential Oral Treatment for Visceral Leishmaniasis
Authors: Patterson Stephen , Wyllie Susan , Stojanovski Laste , Perry Meghan R. , Simeons Frederick R. C. , Norval Suzanne , Osuna-Cabello Maria , De Rycker Manu , Read Kevin D. , Fairlamb Alan H. 
Published: July 2013

ABSTRACT

The novel nitroimidazopyran agent (
S
)-PA-824 has potent antibacterial activity against
Mycobacterium tuberculosis
in vitro
and
in vivo
and is currently in phase II clinical trials for tuberculosis (TB). In contrast to
M. tuberculosis
, where (
R
)-PA-824 is inactive, we report here that both enantiomers of PA-824 show potent parasiticidal activity against
Leishmania donovani
, the causative agent of visceral leishmaniasis (VL). In leishmania-infected macrophages, (
R
)-PA-824 is 6-fold more active than (
S
)-PA-824. Both des-nitro analogues are inactive, underlining the importance of the nitro group in the mechanism of action. Although the
in vitro
and
in vivo
pharmacological profiles of the two enantiomers are similar, (
R
)-PA-824 is more efficacious in the murine model of VL, with >99% suppression of parasite burden when administered orally at 100 mg kg of body weight
−1
, twice daily for 5 days. In
M. tuberculosis
, (
S
)-PA-824 is a prodrug that is activated by a deazaflavin-dependent nitroreductase (Ddn), an enzyme which is absent in
Leishmania
spp. Unlike the case with nifurtimox and fexinidazole, transgenic parasites overexpressing the leishmania nitroreductase are not hypersensitive to either (
R
)-PA-824 or (
S
)-PA-824, indicating that this enzyme is not the primary target of these compounds. Drug combination studies
in vitro
indicate that fexinidazole and (
R
)-PA-824 are additive whereas (
S
)-PA-824 and (
R
)-PA-824 show mild antagonistic behavior. Thus, (
R
)-PA-824 is a promising candidate for late lead optimization for VL and may have potential for future use in combination therapy with fexinidazole, currently in phase II clinical trials against VL.
DNA Microarray for Genotyping Antibiotic Resistance Determinants in Acinetobacter baumannii Clinical Isolates
Authors: Dally Simon , Lemuth Karin , Kaase Martin , Rupp Steffen , Knabbe Cornelius , Weile Jan 
Published: July 2013

ABSTRACT

In recent decades,
Acinetobacter baumannii
has emerged as an organism of great concern due to its ability to accumulate antibiotic resistance. In order to improve the diagnosis of resistance determinants in
A. baumannii
in terms of lead time and accuracy, we developed a microarray that can be used to detect 91 target sequences associated with antibiotic resistance within 4 h from bacterial culture to result. The array was validated with 60 multidrug-resistant strains of
A. baumannii
in a blinded, prospective study. The results were compared to phenotype results determined by the automated susceptibility testing system VITEK2. Antibiotics considered were piperacillin-tazobactam, ceftazidime, imipenem, meropenem, trimethoprim-sulfamethoxazole, amikacin, gentamicin, tobramycin, ciprofloxacin, and tigecycline. The average positive predictive value, negative predictive value, sensitivity, and specificity were 98, 98, 99, and 94%, respectively. For carbapenemase genes, the array results were compared to singleplex PCR results provided by the German National Reference Center for Gram-Negative Pathogens, and results were in complete concordance. The presented array is able to detect all relevant resistance determinants of
A. baumannii
in parallel. The short handling time of 4 h from culture to result helps to provide fast results in order to initiate adequate anti-infective therapy for critically ill patients. Another application would be data acquisition for epidemiologic surveillance.
Basis for Early and Preferential Selection of the E138K Mutation in HIV-1 Reverse Transcriptase
Authors: McCallum Matthew , Oliveira Maureen , Ibanescu Ruxandra-Ilinca , Kramer Victor G. , Moisi Daniela , Asahchop Eugene L. , Brenner Bluma G. , Harrigan P. Richard , Xu Hongtao , Wainberg Mark A. 
Published: July 2013

ABSTRACT
E138K, a G→A mutation in HIV-1 reverse transcriptase (RT), is preferentially selected by etravirine (ETR) and rilpivirine over other substitutions at position E138 that offer greater drug resistance. We hypothesized that there was a mutational bias for the E138K substitution and designed an allele-specific PCR to monitor the emergence of E138A/G/K/Q/R/V during ETR selection experiments. We also performed competition experiments using mutated viruses and quantified the prevalence of E138 minority species in drug-naive patients. E138K, as well as E138G, consistently emerged first during ETR selection experiments, followed by E138A and E138Q; E138R was never selected. Surprisingly, E138K was identified as a tiny minority in 23% of drug-naive subtype B patients, a result confirmed by ultradeep sequencing (UDS). This result could reflect a low fitness cost of E138K; however, E138K was one of the least fit substitutions at codon E138, even after taking into account the deoxynucleoside triphosphate pools of the cells used in competition experiments. Further UDS analysis revealed other minority species in a pattern consistent with the mutational bias of HIV RT. There was no evidence of APOBEC3-hypermutation in these selection experiments or in patients. Our results confirm the mutational bias of HIV-1 in patients and highlight the importance of G→A mutations in HIV-1 drug resistance evolution.
Abiotic and Microbiotic Factors Controlling Biofilm Formation by Thermophilic Sporeformers
Authors: Zhao Yu , Caspers Martien P. M. , Metselaar Karin I. , de Boer Paulo , Roeselers Guus , Moezelaar Roy , Nierop Groot Masja , Montijn Roy C. , Abee Tjakko , Kort Remco 
Published: July 2013

ABSTRACT

One of the major concerns in the production of dairy concentrates is the risk of contamination by heat-resistant spores from thermophilic bacteria. In order to acquire more insight in the composition of microbial communities occurring in the dairy concentrate industry, a bar-coded 16S amplicon sequencing analysis was carried out on milk, final products, and fouling samples taken from dairy concentrate production lines. The analysis of these samples revealed the presence of DNA from a broad range of bacterial taxa, including a majority of mesophiles and a minority of (thermophilic) spore-forming bacteria. Enrichments of fouling samples at 55°C showed the accumulation of predominantly
Brevibacillus
and
Bacillus
, whereas enrichments at 65°C led to the accumulation of
Anoxybacillus
and
Geobacillus
species. Bacterial population analysis of biofilms grown using fouling samples as an inoculum indicated that both
Anoxybacillus
and
Geobacillus
preferentially form biofilms on surfaces at air-liquid interfaces rather than on submerged surfaces. Three of the most potent biofilm-forming strains isolated from the dairy factory industrial samples, including
Geobacillus thermoglucosidans
,
Geobacillus stearothermophilus
, and
Anoxybacillus flavithermus
, have been characterized in detail with respect to their growth conditions and spore resistance. Strikingly,
Geobacillus thermoglucosidans
, which forms the most thermostable spores of these three species, is not able to grow in dairy intermediates as a pure culture but appears to be dependent for growth on other spoilage organisms present, probably as a result of their proteolytic activity. These results underscore the importance of abiotic and microbiotic factors in niche colonization in dairy factories, where the presence of thermophilic sporeformers can affect the quality of end products.
The Evolutionary Divergence of Shiga Toxin-Producing Escherichia coli Is Reflected in Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) Spacer Composition
Authors: Yin Shuang , Jensen Mark A. , Bai Jiawei , DebRoy Chitrita , Barrangou Rodolphe , Dudley Edward G. 
Published: July 2013

ABSTRACT

The Shiga toxin-producing
Escherichia coli
(STEC) strains, including those of O157:H7 and the “big six” serogroups (i.e., serogroups O26, O45, O103, O111, O121, and O145), are a group of pathogens designated food adulterants in the United States. The relatively conserved nature of
c
lustered
r
egularly
i
nterspaced
s
hort
p
alindromic
r
epeats (CRISPRs) in phylogenetically related
E. coli
strains makes them potential subtyping markers for STEC detection, and a quantitative PCR (qPCR)-based assay was previously developed for O26:H11, O45:H2, O103:H2, O111:H8, O121:H19, O145:H28, and O157:H7 isolates. To better evaluate the sensitivity and specificity of this qPCR method, the CRISPR loci of 252 O157 and big-six STEC isolates were sequenced and analyzed along with 563 CRISPR1 and 624 CRISPR2 sequences available in GenBank. General conservation of spacer content and order was observed within each O157 and big-six serogroup, validating the qPCR method. Meanwhile, it was found that spacer deletion, the presence of an insertion sequence, and distinct alleles within a serogroup are sources of false-negative reactions. Conservation of CRISPR arrays among isolates expressing the same flagellar antigen, specifically, H7, H2, and H11, suggested that these isolates share an ancestor and provided an explanation for the false positives previously observed in the qPCR results. An analysis of spacer distribution across
E. coli
strains provided limited evidence for temporal spacer acquisition. Conversely, comparison of CRISPR sequences between strains along the stepwise evolution of O157:H7 from its O55:H7 ancestor revealed that, over this ∼7,000-year span, spacer deletion was the primary force generating CRISPR diversity.
Generation of Affinity-Tagged Fluoromycobacteriophages by Mixed Assembly of Phage Capsids
Authors: Piuri Mariana , Rondón Liliana , Urdániz Estefanía , Hatfull Graham F. 
Published: July 2013

ABSTRACT
Addition of affinity tags to bacteriophage particles facilitates a variety of applications, including vaccine construction and diagnosis of bacterial infections. Addition of tags to phage capsids is desirable, as modification of the tails can lead to poor adsorption and loss of infectivity. Although tags can readily be included as fusions to head decoration proteins, many phages do not have decoration proteins as virion components. The addition of a small (10-amino-acid) Strep-tag II (STAG II) to the mycobacteriophage TM4 capsid subunit, gp9, was not tolerated as a genetically homogenous recombinant phage but could be incorporated into the head by growth of wild-type phage on a host expressing the capsid-STAG fusion. Particles with capsids composed of wild-type and STAG-tagged subunit mixtures could be grown to high titers, showed good infectivities, and could be used to isolate phage-bacterium complexes. Preparation of a STAG-labeled fluoromycobacteriophage enabled capture of bacterial complexes and identification of infected bacteria by fluorescence.