Spectrochemical analysis of liquid biopsy harnessed to multivariate analysis towards breast cancer screening

Mortality due to breast cancer could be reduced via screening programs where preliminary clinical tests employed in an asymptomatic well-population with the objective of identifying cancer biomarkers could allow earlier referral of women with altered results for deeper clinical analysis and treatment. The introduction of well-population screening using new and less-invasive technologies as a strategy for earlier detection of breast cancer is thus highly desirable. Herein, spectrochemical analyses harnessed to multivariate classification techniques are used as a bio-analytical tool for a Breast Cancer Screening Program using liquid biopsy in the form of blood plasma samples collected from 476 patients recruited over a 2-year period. This methodology is based on acquiring and analysing the spectrochemical fingerprint of plasma samples by attenuated total reflection Fourier-transform infrared spectroscopy; derived spectra reflect intrinsic biochemical composition, generating information on nucleic acids, carbohydrates, lipids and proteins. Excellent results in terms of sensitivity (94%) and specificity (91%) were obtained using this method in comparison with traditional mammography (88–93% and 85–94%, respectively). Additional advantages such as better disease prognosis thus allowing a more effective treatment, lower associated morbidity, fewer false-positive and false-negative results, lower-cost, and higher analytical frequency make this method attractive for translation to the clinical setting

Adult body growth and reproductive investment vary markedly within and across Atlantic and Pacific herring: a meta-analysis and review of 26 stocks

Life-history traits of Pacific (Clupea pallasii) and Atlantic (Clupea harengus) herring, comprising both local and oceanic stocks subdivided into summer-autumn and spring spawners, were extensively reviewed. The main parameters investigated were body growth, condition, and reproductive investment. Body size of Pacific herring increased with increasing latitude. This pattern was inconsistent for Atlantic herring. Pacific and local Norwegian herring showed comparable body conditions, whereas oceanic Atlantic herring generally appeared stouter. Among Atlantic herring, summer and autumn spawners produced many small eggs compared to spring spawners, which had fewer but larger eggs—findings agreeing with statements given several decades ago. The 26 herring stocks we analysed, when combined across distant waters, showed clear evidence of a trade-off between fecundity and egg size. The size-specific individual variation, often ignored, was substantial. Additional information on biometrics clarified that oceanic stocks were generally larger and had longer life spans than local herring stocks, probably related to their longer feeding migrations. Body condition was only weakly, positively related to assumingly in situ annual temperatures (0–30 m depth). Contrarily, body growth (cm × y−1), taken as an integrator of ambient environmental conditions, closely reflected the extent of investment in reproduction. Overall, Pacific and local Norwegian herring tended to cluster based on morphometric and reproductive features, whereas oceanic Atlantic herring clustered separately. Our work underlines that herring stocks are uniquely adapted to their habitats in terms of trade-offs between fecundity and egg size whereas reproductive investment mimics the productivity of the water in question.publishedVersio

He II lambda-4686 in Eta Carinae: Collapse of the Wind-Wind Collision Region During Periastron Passage

The periodic spectroscopic events in Eta Carinae are now well established and occur near the periastron passage of two massive stars in a very eccentric orbit. Several mechanisms have been proposed to explain the variations of different spectral features, such as an eclipse by the wind-wind collision boundary, a shell ejection from the primary star or accretion of its wind onto the secondary. All of them have problems explaining all the observed phenomena. To better understand the nature of the cyclic events we performed a dense monitoring of Eta Carinae with 5 Southern telescopes during the 2009 low excitation event, resulting in a set of data of unprecedented quality and sampling. The intrinsic luminosity of the He II lambda-4686 emission line (L approx 310 solar L) just before periastron reveals the presence of a very luminous transient source of extreme UV radiation emitted in the wind-wind collision (WWC) region. Clumps in the primary's wind probably explain the flare-like behavior of both the X-ray and He II lambda-4686 light-curves. After a short-lived minimum, He II lambda-4686 emission rises again to a new maximum, when X-rays are still absent or very weak. We interpret this as a collapse of the WWC onto the "surface" of the secondary star, switching off the hard X-ray source and diminishing the WWC shock cone. The recovery from this state is controlled by the momentum balance between the secondary's wind and the clumps in the primary's wind

MicroScope: a platform for microbial genome annotation and comparative genomics

The initial outcome of genome sequencing is the creation of long text strings written in a four letter alphabet. The role of in silico sequence analysis is to assist biologists in the act of associating biological knowledge with these sequences, allowing investigators to make inferences and predictions that can be tested experimentally. A wide variety of software is available to the scientific community, and can be used to identify genomic objects, before predicting their biological functions. However, only a limited number of biologically interesting features can be revealed from an isolated sequence. Comparative genomics tools, on the other hand, by bringing together the information contained in numerous genomes simultaneously, allow annotators to make inferences based on the idea that evolution and natural selection are central to the definition of all biological processes. We have developed the MicroScope platform in order to offer a web-based framework for the systematic and efficient revision of microbial genome annotation and comparative analysis (http://www.genoscope.cns.fr/agc/microscope). Starting with the description of the flow chart of the annotation processes implemented in the MicroScope pipeline, and the development of traditional and novel microbial annotation and comparative analysis tools, this article emphasizes the essential role of expert annotation as a complement of automatic annotation. Several examples illustrate the use of implemented tools for the review and curation of annotations of both new and publicly available microbial genomes within MicroScope’s rich integrated genome framework. The platform is used as a viewer in order to browse updated annotation information of available microbial genomes (more than 440 organisms to date), and in the context of new annotation projects (117 bacterial genomes). The human expertise gathered in the MicroScope database (about 280,000 independent annotations) contributes to improve the quality of microbial genome annotation, especially for genomes initially analyzed by automatic procedures alone

Methylobacterium Genome Sequences: A Reference Blueprint to Investigate Microbial Metabolism of C1 Compounds from Natural and Industrial Sources

Methylotrophy describes the ability of organisms to grow on reduced organic compounds without carbon-carbon bonds. The genomes of two pink-pigmented facultative methylotrophic bacteria of the Alpha-proteobacterial genus Methylobacterium, the reference species Methylobacterium extorquens strain AM1 and the dichloromethane-degrading strain DM4, were compared. Methodology/Principal Findings The 6.88 Mb genome of strain AM1 comprises a 5.51 Mb chromosome, a 1.26 Mb megaplasmid and three plasmids, while the 6.12 Mb genome of strain DM4 features a 5.94 Mb chromosome and two plasmids. The chromosomes are highly syntenic and share a large majority of genes, while plasmids are mostly strain-specific, with the exception of a 130 kb region of the strain AM1 megaplasmid which is syntenic to a chromosomal region of strain DM4. Both genomes contain large sets of insertion elements, many of them strain-specific, suggesting an important potential for genomic plasticity. Most of the genomic determinants associated with methylotrophy are nearly identical, with two exceptions that illustrate the metabolic and genomic versatility of Methylobacterium. A 126 kb dichloromethane utilization (dcm) gene cluster is essential for the ability of strain DM4 to use DCM as the sole carbon and energy source for growth and is unique to strain DM4. The methylamine utilization (mau) gene cluster is only found in strain AM1, indicating that strain DM4 employs an alternative system for growth with methylamine. The dcm and mau clusters represent two of the chromosomal genomic islands (AM1: 28; DM4: 17) that were defined. The mau cluster is flanked by mobile elements, but the dcm cluster disrupts a gene annotated as chelatase and for which we propose the name “island integration determinant” (iid).Conclusion/Significance These two genome sequences provide a platform for intra- and interspecies genomic comparisons in the genus Methylobacterium, and for investigations of the adaptive mechanisms which allow bacterial lineages to acquire methylotrophic lifestyles.Organismic and Evolutionary Biolog

Don't Fall Off the Adaptation Cliff: When Asymmetrical Fitness Selects for Suboptimal Traits

The cliff-edge hypothesis introduces the counterintuitive idea that the trait value associated with the maximum of an asymmetrical fitness function is not necessarily the value that is selected for if the trait shows variability in its phenotypic expression. We develop a model of population dynamics to show that, in such a system, the evolutionary stable strategy depends on both the shape of the fitness function around its maximum and the amount of phenotypic variance. The model provides quantitative predictions of the expected trait value distribution and provides an alternative quantity that should be maximized (“genotype fitness”) instead of the classical fitness function (“phenotype fitness”). We test the model's predictions on three examples: (1) litter size in guinea pigs, (2) sexual selection in damselflies, and (3) the geometry of the human lung. In all three cases, the model's predictions give a closer match to empirical data than traditional optimization theory models. Our model can be extended to most ecological situations, and the evolutionary conditions for its application are expected to be common in nature

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

Four Regional Marine Biodiversity Studies: Approaches and Contributions to Ecosystem-Based Management

We compare objectives and approaches of four regional studies of marine biodiversity: Gulf of Maine Area Census of Marine Life, Baltic Sea History of Marine Animal Populations, Great Barrier Reef Seabed Biodiversity Project, and Gulf of Mexico Biodiversity Project. Each program was designed as an "ecosystem" scale but was created independently and executed differently. Each lasted 8 to 10 years, including several years to refine program objectives, raise funding, and develop research networks. All resulted in improved baseline data and in new, or revised, data systems. Each contributed to the creation or evolution of interdisciplinary teams, and to regional, national, or international science-management linkages. To date, there have been differing extents of delivery and use of scientific information to and by management, with greatest integration by the program designed around specific management questions. We evaluate each research program's relative emphasis on three principal elements of biodiversity organization: composition, structure, and function. This approach is used to analyze existing ecosystem-wide biodiversity knowledge and to assess what is known and where gaps exist. In all four of these systems and studies, there is a relative paucity of investigation on functional elements of biodiversity, when compared with compositional and structural elements. This is symptomatic of the current state of the science. Substantial investment in understanding one or more biodiversity element(s) will allow issues to be addressed in a timely and more integrative fashion. Evaluating research needs and possible approaches across specific elements of biodiversity organization can facilitate planning of future studies and lead to more effective communication between scientists, managers, and stakeholders. Building a general approach that captures how various studies have focused on different biodiversity elements can also contribute to meta-analyses of worldwide experience in scientific research to support ecosystem-based management