bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary patterns–tested with cladistics–and processes in relation to palaeoenvironments of the Upper Barremian genus Gassendiceras (Ammonitina, Lower Cretaceous)
Authors: BERT DIDIER , BERSAC STÉPHANE 
Published: January 2013

Abstract:  Phylogenetic reconstruction of the Upper Barremian ammonite genus Gassendiceras (Gassendiceratinae) was performed using a cladistic analysis incorporating continuous data. Some morphological features were found to vary identically among all the analysed species and therefore carry no phylogenetic information (= symplesiomorphic). The single obtained cladogram allows interpreting the evolution of the Gassendiceras as an anagenetic succession of eight species, in stratigraphic order of appearance, Gassendiceras multicostatum, G. alpinum, G. hoheneggeri, G. rebouleti, G. bosellii, G. quelquejeui, G. coulletae and G. enayi. The clade Pseudoshasticrioceras/Imerites is derived from G. enayi, so the genus Gassendiceras appears to be paraphyletic. But here, we accept this fact as the best evolutive classification. The evolution over time of Gassendiceras is modulated by some processes, which could have constrained the inferred phylogenetic pattern with the drift of the global variability towards the most gracile forms over time. It is tempting to interpret this evolution as a constant selection over time of the Gassendiceras modulated by environmental control due to eustatic variation across a transgressive sequence. Thus, the most peramorphic (gracile) individuals seemed favoured at the expense of those most robust (paedomorphic).
Association between putative functional variants in the PSMB9 gene and risk of melanoma – re‐analysis of published melanoma genome‐wide association studies
Authors: Qian Ji , Liu Hongliang , Wei Sheng , Liu Zhensheng , Li Yangkai , Wang Li‐E , Chen Wei V. , Amos Christopher I. , Lee Jeffrey E. ,   GenoMEL investigators, Iles Mark M. , Law Matthew H. ,   Q‐MEGA AMFS investigators, Cust Anne E. , Barrett Jennifer H. , Montgomery Grant W. , Taylor John , Bishop Julia A. Newton , MacGregor Stuart , Bishop D. Timothy , Mann Graham J. , Hayward Nicholas K. , Wei Qingyi 
Published: January 2013

SummaryTo mine possibly hidden causal single‐nucleotide polymorphisms (SNPs) of melanoma, we investigated the association of SNPs in 76 M/G1 transition genes with melanoma risk using our published genome‐wide association study (GWAS) data set with 1804 melanoma cases and 1026 cancer‐free controls. We found multiple SNPs with P < 0.01 and performed validation studies for 18 putative functional SNPs in PSMB9 in two other GWAS data sets. Two SNPs (rs1351383 and rs2127675) were associated with melanoma risk in the GenoMEL data set (P = 0.013 and 0.004, respectively), but failed in validation using the Australian data set. Genotype–phenotype analysis revealed these two SNPs were significantly correlated with mRNA expression level of PSMB9. Further experiments revealed that SNP rs2071480, which is in high LD with rs1351383 and rs2127675, may have a weak effect on the promoter activity of PSMB9. Taken together, our data suggested that functional variants in PSMB9 may contribute to melanoma susceptibility.
Theoretical Study of Firefly Luciferin pKa Values—Relative Absorption Intensity in Aqueous Solutions
Authors: Hiyama Miyabi , Akiyama Hidefumi , Yamada Kenta , Koga Nobuaki 
Published: January 2013

AbstractGround‐state vibrational analyses of firefly luciferin and its conjugate acids and bases are performed. The Gibbs free energies obtained from these analyses are used to estimate pKa values for phenolic hydroxy and carboxy groups and the N–H+ bond in the N‐protonated thiazoline or benzothiazole ring of firefly luciferin. The theoretical pKa values are corrected using the experimental values. The concentrations of these chemical species in solutions with different pH values are estimated from their corrected pKa values, and the pH dependence of their relative absorption intensities is elucidated. With the results obtained we assign the experimental spectra unequivocally. Especially, the small peak near 400 nm at pH 1–2 in experimental absorption spectra is clarified to be due to the excitation of carboxylate anion with N‐protonated thiazoline ring of firefly luciferin. Our results show that the pKa values of chemical species, which are contained in the aqueous solutions, are effective to assign experimental absorption spectra.
Fluorescence Spectroscopy of the Retina from Scrapie‐Infected Mice
Authors: Bose Sayantan , Schönenbrücher Holger , Richt Jürgen A. , Casey Thomas A. , Rasmussen Mark A. , Kehrli Marcus E. , Petrich Jacob W. 
Published: January 2013

AbstractRecently, we have proposed that the fluorescence spectra of sheep retina can be well correlated with the presence or absence of scrapie. Scrapie is the most widespread TSE (transmissible spongiform encephalopathy) affecting sheep and goats worldwide. Mice eyes have been previously reported as a model system to study age‐related accumulation of lipofuscin, which has been investigated by monitoring the increasing fluorescence with age covering its entire life span. The current work aims at developing mice retina as a convenient model system to diagnose scrapie and other fatal TSE diseases in animals such as sheep and cows. The objective of the research reported here was to determine whether the spectral features are conserved between two different species namely mice and sheep, and whether an appropriate small animal model system could be identified for diagnosis of scrapie based on the fluorescence intensity in retina. The results were consistent with the previous reports on fluorescence studies of healthy and scrapie‐infected retina of sheep. The fluorescence from the retinas of scrapie‐infected sheep was significantly more intense and showed more heterogeneity than that from the retinas of uninfected mice. Although the structural characteristics of fluorescence spectra of scrapie‐infected sheep and mice eyes are slightly different, more importantly, murine retinas reflect the enhancement of fluorescence intensity upon infecting the mice with scrapie, which is consistent with the observations in sheep eyes.
Variability of Memory B cell Markers in a Cohort of Common Variable Immune Deficiency Patients over 6 months
Authors: Koopmans W. , Woon S.‐T. , Zeng I. S. L. , Jordan A. , Brothers S. , Browett P. , Ameratunga R. 
Published: January 2013

AbstractCommon Variable Immunodeficiency Disorder (CVID) is a complex disorder that predisposes patients to recurrent and severe infections. Immunophenotypic classification schemes were developed to categorize patients with CVID into phenotypic and prognostic groups based on different memory B cell subsets. Whether the B cell subset analysis is stable over time has not been investigated. B cell phenotyping in patients with CVID (n = 15) and sex‐ and age‐matched controls (n = 26) were carried out according to the three B cell classifications. Patients with CVID were evaluated monthly over 6 months. Controls were assessed once during the study. We scored how often each patient was assigned to the same group within each classification. The Freiburg classification assigned patients to the same group at a rate of 73% and the Paris classification at 88%. The EUROclass classification of smB− versus smB+ was at 90%. The two subclassifications [(smB‐21low or smB‐21norm) and transitional B] were at 87% and 97%, respectively. The level of naïve B cells measured in all patients with CVID during the 6‐month evaluation was the most stable B cell subset. We conclude that all classifications systems show considerable variability, but the EUROclass classification was the most reliable scheme for our 15 CVID and 26 healthy cohorts. Our results indicate that phenotypic classifications within CVID will be difficult while there is variability of commonly used assays.
Cross‐border Economic Activities, Human Capital and Efficiency: A Stochastic Frontier Analysis for OECD Countries
Authors: Ghosh Sucharita , Mastromarco Camilla 
Published: January 2013

AbstractWe study the growth effects of outward‐ori,ented econ,o,mies by using sto,chas,tic fron,tier anal,y,sis to mea,sure the effi,ciency exter,nal,i,ties of three forms of eco,n,omic cross‐bor,der activ,i,ties – inter,na,tional trade, for,eign direct invest,ment (FDI) and migra,tion – for OECD coun,tries. The study also exam,ines whether the effi,ciency of these cross‐bor,der activ,i,ties is affected by the level of human cap,i,tal in the host coun,try. We find that inter,na,tional trade and FDI are impor,tant chan,nels for improv,ing effi,ciency, as is human cap,i,tal accu,mu,la,tion, and that the positive effects of inter,na,tional trade, FDI, and migra,tion depend cru,cially on the level of accu,mu,lated human cap,i,tal. Our results show that the impact of human cap,i,tal is impor,tant for increas,ing effi,ciency via inter,na,tional trade flows and FDI flows, while immi,gra,tion into coun,tries that are richer in human cap,i,tal enhances their effi,ciency rel,a,tively more than immi,gra,tion into coun,tries with lower human cap,i,tal. These results remain robust to alter,nate mea,sures of human cap,i,tal, con,trols on edu,ca,tion lev,els among immi,grants, and to a non‐para,met,ric esti,ma,tion of the model.
Corneal collagen cross‐linking (CXL) for the treatment of melting keratitis in cats and dogs: a pilot study
Authors: Spiess Bernhard M. , Pot Simon A. , Florin Marion , Hafezi Farhad 
Published: January 2013

AbstractObjectiveUV‐A/riboflavin cross‐linking (CXL) of corneal collagen fibers is an established, highly promising therapy for corneal melting in physician‐based ophthalmology. A prospective pilot study was conducted to demonstrate proof of principle of this novel method for the treatment of melting corneal ulcers in dogs and cats.ProceduresAfter obtaining owner consent,CXLwas performed in three cats and three dogs with corneal melting, which either affected the entire corneal surface or was resistant to conventional antibiotic and anticollagenolytic therapy, and affected parts or all of the corneal surface. Medical therapy was continued in all patients. The available follow‐up ranged from 2 to 22.5 months and involved slit‐lamp examination, fluorescein staining, and photographic documentation during all rechecks.ResultsSurgical stabilization of the cornea was not necessary in any case, because progression of corneal melting was arrested in all cases within 1–20 days ofCXLtreatment. Corneal re‐epithelization occurred within 7–40 days in all eyes. At 40 days afterCXL, all eyes presented a quiescent corneal state without signs of active inflammation and with beginning scar formation. The complications observed in three of the six animals included a corneal sequestrum, superficial corneal stromal pigmentation, and bullous keratopathy.ConclusionsThis study shows the feasibility ofCXLto treat progressive corneal melting in veterinary patients.CXLmay represent a cost‐efficient and safe alternative therapy in the treatment for corneal melting in veterinary ophthalmology. More investigations comparing the effectivity and complication rate ofCXLto those of standard medical treatment are necessary.
Assessment of the use of spectral domain optical coherence tomography (SD‐OCT) for evaluation of the healthy and pathological cornea in dogs and cats
Authors: Famose Frank 
Published: January 2013

AbstractPurposeMorphologic evaluation of the cornea is based on the slit‐lamp examination. In human ophthalmology, optical coherence tomography (OCT) has opened a new field in the clinical approach to anterior segment disorders and more specifically the cornea. The aim of our study is to describe spectral domainOCTexamination of the cornea in dogs and cats in clinical practice conditions.Material and methodsOne hundred eyes were examined from 52 dogs and 41 cats presented to a private practice referral center with an Optovue iVue SD‐OCT device. Sixteen healthy animals were used as control group, and the others were examined for various corneal conditions. All animals were examined after sedation or anesthesia.ResultsNormal and pathological aspects of canine and feline cornea were described for various conditions such as corneal ulcers, microbial keratitis, corneal sequestrum, infiltrations, foreign bodies, corneal dystrophies, and surgical conditions.ConclusionSD‐OCTexamination of normal and pathological corneal conditions in dogs and cats gave an accurate evaluation of each component of the cornea. The advantage of the technique is thein vivo, real‐time evaluation of all corneal layers with the absence of corneal contact. Constraints included the necessity of sedation for precise focus and the low quality of images obtained with too pigmented or thickened corneas.
The essential role of peripheral respiratory chemoreceptor inputs in maintaining breathing revealed when CO2 stimulation of central chemoreceptors is diminished
Authors: Fiamma Marie‐Noëlle , O’Connor Edward T. , Roy Arijit , Zuna Ines , Wilson Richard J. A. 
Published: January 2013

Key points
Central sleep apnoea is a condition characterized by oscillations between apnoea and hyperpnoea during sleep, which can have many serous health implications.
Each ventilatory overshoot following an apnoea attenuates peripheral chemoreceptor input which, in turn, has the potential to cause a further apnoea.
In a decerebrate, vagotomized, in situ rat preparation, we show that central apnoeas can be overcome both physiologically (with high peripheral CO2) and pharmacologically (with peripheral pituitary adenylate cyclase‐activating peptide).
We also show that the central apnoeic threshold, i.e. the CO2 level at which the animal stops breathing, can be lowered by increasing peripheral chemoreceptor stimulation.
These data suggest that stimulation of peripheral chemoreceptors may prevent central apnoeas, re‐affirming the peripheral chemoreceptors as possible therapeutic targets for some sleep apnea phenotypes.
Abstract  Central sleep apnoea is a condition characterized by oscillations between apnoea and hyperpnoea during sleep. Studies in sleeping dogs suggest that withdrawal of peripheral chemoreceptor (carotid body) activation following transient ventilatory overshoots plays an essential role in causing apnoea, raising the possibility that sustaining carotid body activity during ventilatory overshoots may prevent apnoea. To test whether sustained peripheral chemoreceptor activation is sufficient to drive breathing, even in the absence of central chemoreceptor stimulation and vagal feedback, we used a vagotomized, decerebrate dual‐perfused in situ rat preparation in which the central and peripheral chemoreceptors are independently and artificially perfused with gas‐equilibrated medium. At varying levels of carotid body stimulation (CB PO2/PCO2: 40/60, 100/40, 200/15, 500/15 Torr), we decreased the brainstem perfusate PCO2 in 5 Torr steps while recording phrenic nerve activity to determine the central apnoeic thresholds. The central apnoeic thresholds decreased with increased carotid body stimulation. When the carotid bodies were strongly stimulated (CB 40/60), the apnoeic threshold was 3.6 ± 1.4 Torr PCO2 (mean ± SEM, n = 7). Stimulating carotid body afferent activity with either hypercapnia (60 Torr PCO2) or the neuropeptide pituitary adenylate cyclase‐activating peptide restored phrenic activity during central apnoea. We conclude that peripheral stimulation shifts the central apnoeic threshold to very hypocapnic levels that would likely increase the CO2 reserve and have a protective effect on breathing. These data demonstrate that peripheral respiratory chemoreceptors are sufficient to stave off central apnoeas when the brainstem is perfused with low to no CO2.
Gastrin‐releasing peptide acts via postsynaptic BB2 receptors to modulate inward rectifier K+ and TRPV1‐like conductances in rat paraventricular thalamic neurons
Authors: Hermes M. L. H. J. , Kolaj M. , Coderre E. M. , Renaud L. P. 
Published: January 2013

Key points
Gastrin‐releasing peptide (GRP) is a mammalian bombesin‐like peptide that is widely distributed in the CNS. Whereas GRP is known to have a predominant excitatory action on neurons, details of the underlying membrane mechanism remain largely undefined.
We investigated GRP‐affected receptors and ionic conductances in the midline paraventricular thalamic nucleus, a brain region densely innervated by GRP‐like immunoreactive fibres.
Perforated patch clamp recording in acute brain slices showed that exposure of paraventricular thalamic nucleus neurons to low nanomolar concentrations of GRP resulted in membrane depolarization with rhythmic burst or tonic firing. These responses were due to a postsynaptic bombesin type 2 receptor‐mediated simultaneous suppression of a Ba2+‐sensitive inward rectifier K+ conductance and activation of a non‐selective cation conductance with transient receptor potential vanilloid 1‐like properties.
The data provide details on the nature of the receptor and ionic conductances involved in GRP's excitatory influence on midline thalamic neurons.
Abstract  Gastrin‐releasing peptide (GRP) is a bombesin‐like peptide with a widespread distribution in mammalian CNS, where it has a role in food intake, circadian rhythm generation, fear memory, itch sensation and sexual behaviour. While it has been established that GRP predominantly excites neurons, details of the membrane mechanism involved in this action remain largely undefined. We used perforated patch clamp recording in acute brain slice preparations to investigate GRP‐affected receptors and ionic conductances in neurons of the rat paraventricular thalamic nucleus (PVT). PVT is a component of the midline and intralaminar thalamus that participates in arousal, motivational drives and stress responses, and exhibits a prominence of GRP‐like immunoreactive fibres. Exposure of PVT neurons to low nanomolar concentrations of GRP induced sustained TTX‐resistant membrane depolarizations that could trigger rhythmic burst discharges or tonic firing. Membrane current analyses in voltage clamp revealed an underlying postsynaptic bombesin type 2 receptor‐mediated inward current that resulted from the simultaneous suppression of a Ba2+‐sensitive inward rectifier K+ conductance and activation of a non‐selective cation conductance with biophysical and pharmacological properties reminiscent of transient receptor potential vanilloid (TRPV) 1. A role for a TRPV1‐like conductance was further implied by a significant suppressant influence of a TRPV1 antagonist on GRP‐induced membrane depolarization and rhythmic burst or tonic firing. The results provide a detailed picture of the receptor and ionic conductances that are involved in GRP's excitatory action in midline thalamus.
Chimeric Beta-Defensin Analogs, Including the Novel 3NI Analog, Display Salt-Resistant Antimicrobial Activity and Lack Toxicity in Human Epithelial Cell Lines
Authors: Scudiero Olga , Galdiero Stefania , Nigro Ersilia , Del Vecchio Luigi , Di Noto Rosa , Cantisani Marco , Colavita Irene , Galdiero Massimiliano , Cassiman Jean-Jacques , Daniele Aurora , Pedone Carlo , Salvatore Francesco 
Published: January 2013

ABSTRACT

Human beta-defensins (hBDs) are crucial peptides for the innate immune response and are thus prime candidates as therapeutic agents directed against infective diseases. Based on the properties of wild-type hBD1 and hBD3 and of previously synthesized analogs (1C, 3I, and 3N), we have designed a new analog, 3NI, and investigated its potential as an antimicrobial drug. Specifically, we evaluated the antimicrobial activities of 3NI versus those of hBD1, hBD3, 1C, 3I, and 3N. Our results show that 3NI exerted greater antibacterial activity against
Pseudomonas aeruginosa
,
Escherichia coli
, and
Enterococcus faecalis
than did hBD1 and hBD3, even with elevated salt concentrations. Moreover, its antiviral activity against herpes simplex virus 1 was greater than that of hBD1 and similar to that of hBD3. Subsequently, we investigated the cytotoxic effects of all peptides in three human epithelial carcinoma cell lines: A549 from lung, CaCo-2 from colon, and Capan-1 from pancreas. None of the analogs significantly reduced cell viability versus wild-type hBD1 and hBD3. They did not induce genotoxicity or cause an increase in the number of apoptotic cells. Using confocal microscopy, we also investigated the localization of the peptides during their incubation with epithelial cells and found that they were distributed on the cell surface, from which they were internalized. Finally, we show that hBD1 and hBD3 are characterized by high resistance to serum degradation. In conclusion, the new analog 3NI seems to be a promising anti-infective agent, particularly given its high salt resistance—a feature that is relevant in diseases such as cystic fibrosis.
Pharmacodynamic Variability beyond That Explained by MICs
Authors: Soon Rachel L. , Ly Neang S. , Rao Gauri , Wollenberg Lance , Yang Kuo , Tsuji Brian , Forrest Alan 
Published: January 2013

ABSTRACT

Monte Carlo simulations (MCS) present a powerful tool to evaluate candidate regimens by determining the probability of target attainment. Although these assessments have traditionally incorporated variability in pharmacokinetic (PK) parameters and MICs, consideration of interstrain pharmacodynamic (PD) variability has been neglected. A population PK/PD model was developed for doripenem using murine thigh infection data based on 20 bacterial strains. PK data were fit to a linear two-compartment model with first-order input and elimination processes and an absorption lag time from a separate site (
r
2
> 0.96). PK parameters were utilized to simulate free-drug profiles for various regimens in PD studies, from which the percentage of the dosing interval for which free-drug concentrations exceed the MIC of the targeted strain (%
f
T>MIC) was calculated. Doripenem PD was excellently described with Hill-type models (
r
2
> 0.98); significant differences between mean PD estimates determined using a two-stage approach versus population analyses were not observed (
P
> 0.05); however, the variance in 50% effective concentration (EC
50
) and maximum effect (
E
max
) among strains was much greater using the two-stage approach. Even using the population approach, interstrain variability in EC
50
(coefficient of variation expressed as a percentage [CV%] = 29.2%) and
H
(CV% = 46.1%) parameters was substantive, while the variability in
E
max
(CV% = 19.7%) was modest. This resulted in extensive variability in the range of %
fT
>MIC targets associated with stasis to those associated with a 2-log
10
reduction in bacterial burden (CV% ∼ 50%). It appears that MCS, based on the assumption that PD variability is due to MIC alone, underestimates variability and may consequently underestimate treatment failures.