249 research outputs found
Validation and Clinical Application of a New Liquid Chromatography Coupled to Mass Spectrometry (HPLC-MS) Method for Dalbavancin Quantification in Human Plasma
Dalbavancin (DBV) is an intravenous long-acting second-generation glycolipopeptide antibiotic with high efficacy and excellent tolerability, approved for use in the treatment of Gram-positive skin and skin structure infections (ABSSSI). Nevertheless, little is known about its pharmacokinetic/pharmacodynamic (PK/PD) properties in real life, which is also due to technical challenges in its quantification in human plasma, preventing an effective application of therapeutic drug monitoring (TDM). In fact, DBV has a high affinity to plasma proteins, possibly resulting in poor recovery after extraction procedure. The aim of this study was to validate a simple, cheap and reliable HPLC-MS method for use in TDM, in accordance with FDA and EMA guidelines. The optimized protein precipitation protocol required 50 μL of plasma, while chromatographic analysis could be performed in 12 min/sample. This method fulfilled the guidelines requirements and then, it was applied for routine DBV TDM in patients receiving off-label high doses (two 1500 + 1500 mg weekly infusions instead of 1000 + 500 mg), with normal renal function or undergoing hemodialysis: continuous hemodiafiltration caused a relevant reduction in DBV exposure, while intermittent dialysis showed comparable DBV concentrations with those of patients with normal renal function. This confirmed the eligibility of the presented method for use in TDM and its usefulness in clinical practice
Vicinal silicon surfaces: from step density wave to faceting
This paper investigates faceting mechanisms induced by electromigration in
the regime where atomic steps are transparent. For this purpose we study
several vicinal orientations by means of in-situ (optical diffraction,
electronic microscopy) as well as ex-situ (AFM, microprofilometry)
visualization techniques. The data show that faceting proceeds in two stages.
The first stage is short and leads to the appearance of a step density wave,
with a wavelength roughly independent of the surface orientation. The second
stage is much slower, and leads to the formation of a hill-and-valley
structure, the period of which depends on the initial surface orientation. A
simple continuum model enables us to point out why the wavelength of the step
density wave does not depend on the microscale details of the surface. The
final wavelength is controlled by the competition between elastic step-step
interaction and facet edge energy cost. Finally, the surface stress angular
dependence is shown to emerge as a coarsed-grained picture from the step model.Comment: 26 pages, 9 figure
Secondary contact and admixture between independently invading populations of the Western corn rootworm, diabrotica virgifera virgifera in Europe
The western corn rootworm, Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae), is one of the most destructive pests of corn in North America and is currently invading Europe. The two major invasive outbreaks of rootworm in Europe have occurred, in North-West Italy and in Central and South-Eastern Europe. These two outbreaks originated from independent introductions from North America. Secondary contact probably occurred in North Italy between these two outbreaks, in 2008. We used 13 microsatellite markers to conduct a population genetics study, to demonstrate that this geographic contact resulted in a zone of admixture in the Italian region of Veneto. We show that i) genetic variation is greater in the contact zone than in the parental outbreaks; ii) several signs of admixture were detected in some Venetian samples, in a Bayesian analysis of the population structure and in an approximate Bayesian computation analysis of historical scenarios and, finally, iii) allelic frequency clines were observed at microsatellite loci. The contact between the invasive outbreaks in North-West Italy and Central and South-Eastern Europe resulted in a zone of admixture, with particular characteristics. The evolutionary implications of the existence of a zone of admixture in Northern Italy and their possible impact on the invasion success of the western corn rootworm are discussed
Using the Wigner-Ibach Surmise to Analyze Terrace-Width Distributions: History, User's Guide, and Advances
A history is given of the applications of the simple expression generalized
from the surmise by Wigner and also by Ibach to extract the strength of the
interaction between steps on a vicinal surface, via the terrace width
distribution (TWD). A concise guide for use with experiments and a summary of
some recent extensions are provided.Comment: 11 pages, 4 figures, reformatted (with revtex) version of refereed
paper for special issue of Applied Physics A entitled "From Surface Science
to Device Physics", in honor of the retirements of Prof. H. Ibach and Prof.
H. L\"ut
Measuring the surface stress polar dependence
While measurements of the polar dependence of the surface free energy are
easily available, measurements of the whole polar dependence of the surface
stress of a crystal do not exist. In this paper is presented a new procedure
that allows, for the first time, the experimental determination of the surface
stress polar dependence of a crystal. For this purpose (1) electromigration is
used to control the kinetic faceting of surface orientations that belong to the
equilibrium shape of the crystal and (2) for each destabilised surface, the
period of faceting as well as the crystallographic angles of the appearing
facets are measured by AFM. The so-obtained data lead to a set of equations
whose mathematical solution, compatible with physical constraints, gives access
to the surface stress polar dependence of the whole crystal and thus to a
better understanding of surface stress properties.Comment: 8 pages, 6 Figure
Parallel Evolution of a Type IV Secretion System in Radiating Lineages of the Host-Restricted Bacterial Pathogen Bartonella
Adaptive radiation is the rapid origination of multiple species from a single ancestor as the result of concurrent adaptation to disparate environments. This fundamental evolutionary process is considered to be responsible for the genesis of a great portion of the diversity of life. Bacteria have evolved enormous biological diversity by exploiting an exceptional range of environments, yet diversification of bacteria via adaptive radiation has been documented in a few cases only and the underlying molecular mechanisms are largely unknown. Here we show a compelling example of adaptive radiation in pathogenic bacteria and reveal their genetic basis. Our evolutionary genomic analyses of the α-proteobacterial genus Bartonella uncover two parallel adaptive radiations within these host-restricted mammalian pathogens. We identify a horizontally-acquired protein secretion system, which has evolved to target specific bacterial effector proteins into host cells as the evolutionary key innovation triggering these parallel adaptive radiations. We show that the functional versatility and adaptive potential of the VirB type IV secretion system (T4SS), and thereby translocated Bartonella effector proteins (Beps), evolved in parallel in the two lineages prior to their radiations. Independent chromosomal fixation of the virB operon and consecutive rounds of lineage-specific bep gene duplications followed by their functional diversification characterize these parallel evolutionary trajectories. Whereas most Beps maintained their ancestral domain constitution, strikingly, a novel type of effector protein emerged convergently in both lineages. This resulted in similar arrays of host cell-targeted effector proteins in the two lineages of Bartonella as the basis of their independent radiation. The parallel molecular evolution of the VirB/Bep system displays a striking example of a key innovation involved in independent adaptive processes and the emergence of bacterial pathogens. Furthermore, our study highlights the remarkable evolvability of T4SSs and their effector proteins, explaining their broad application in bacterial interactions with the environment
Colonization history of the western corn rootworm (Diabrotica virgifera virgifera) in North America: insights from random forest ABC using microsatellite data
First described from western Kansas, USA, the western corn rootworm, Diabrotica virgifera virgifera, is one of the worst pests of maize. The species is generally thought to be of Mexican origin and to have incidentally followed the expansion of maize cultivation into North America thousands of years ago. However, this hypothesis has never been investigated formally. In this study, the genetic variability of samples collected throughout North America was analysed at 13 microsatellite marker loci to explore precisely the population genetic structure and colonization history of D. v. virgifera. In particular, we used up-to-date approximate Bayesian computation methods based on random forest algorithms to test a Mexican versus a central-USA origin of the species, and to compare various possible timings of colonization. This analysis provided strong evidence that the origin of D. v. virgifera was southern (Mexico, or even further south). Surprisingly, we also found that the expansion of the species north of its origin was recent—probably not before 1100 years ago—thus indicating it was not directly associated with the early history of maize expansion out of Mexico, a far more ancient event
Reconciling the biogeography of an invader through recent and historic genetic patterns: the case of topmouth gudgeon Pseudorasbora parva
© 2018 The Author(s) The genetic variability and population structure of introduced species in their native range are potentially important determinants of their invasion success, yet data on native populations are often poorly represented in relevant studies. Consequently, to determine the contribution of genetic structuring in the native range of topmouth gudgeon Pseudorasbora parva to their high invasion success in Europe, we used a dataset comprising of 19 native and 11 non-native populations. A total of 666 samples were analysed at 9 polymorphic microsatellite loci and sequenced for 597 bp of mitochondrial DNA. The analysis revealed three distinct lineages in the native range, of which two haplogroups were prevalent in China (100%), with a general split around the Qinling Mountains. Dating of both haplogroups closely matched past geological events. More recently, its distribution has been influenced by fish movements in aquaculture, resulting in gene flow between previously separated populations in Northern and Southern China. Their phylogeography in Europe indicate as few as two introductions events and two dispersal routes. Microsatellite data revealed native populations had higher genetic diversity than those in the invasive range, a contrast to previous studies on P. parva. This study confirms the importance of extensive sampling in both the native and non-native range of invasive species in evaluating the influence of genetic variability on invasion success
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