Prediction of survival by neutropenia according to delivery schedule of oxaliplatin-5-Fluorouracil-leucovorin for metastatic colorectal cancer in a randomized international trial (EORTC 05963)

Circadian clocks control cellular proliferation and drug metabolism over the 24?h. However, circadian chronomodulated chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (chronoFLO4) offered no survival benefit as compared with the non-time-stipulated FOLFOX2, in an international randomized trial involving patients with previously untreated metastatic colorectal cancer (EORTC 05963). The authors hypothesized that treatment near maximum tolerated dose could disrupt circadian clocks thus impairing the efficacy of chronoFLO4 but not of FOLFOX2. Patients with available data (N?=?556) were categorized into three subgroups according to the worst grade (G) of neutropenia experienced during treatment. Distinct multivariate models with time-dependent covariates were constructed for each treatment schedule. Neutropenia incidence (all grades) was 33% on chronoFLO4 and 61% on FOLFOX2 (p?相似文献   

Marine-freshwater colonizations of haptophytes inferred from phylogeny of environmental 18S rDNA sequences

The Haptophyta is a common algal group in many marine environments, but only a few species have been observed in freshwaters, with DNA sequences available from just a single species, Crysochromulina parva Lackey, 1939. Here we investigate the haptophyte diversity in a high mountain lake, Lake Finsevatn, Norway, targeting the variable V4 region of the 18S rDNA gene with PCR and 454 pyrosequencing. In addition, the freshwater diversity of Pavlovophyceae was investigated by lineage-specific PCR-primers and clone library sequencing from another Norwegian lake, Lake Svaersvann. We present new freshwater phylotypes belonging to the classes Prymnesiophyceae and Pavlovophyceae, as well as a distinct group here named HAP-1. This is the first molecular evidence of a freshwater species belonging to the class Pavlovophyceae. The HAP-1 and another recently detected marine group (i.e. HAP-2) are separated from both Pavlovophyceae and Prymnesiophyceae and may constitute new higher order taxonomic lineages. As all obtained freshwater sequences of haptophytes are distantly related to the freshwater species C. parva, the phylogeny demonstrates that haptophytes colonized freshwater on multiple independent occasions. One of these colonizations, which gave rise to HAP-1, took place very early in the history of haptophytes, before the radiation of the Prymnesiophyceae.     

Post‐Project Appraisals of River Restoration in Advanced University Instruction

Post‐project appraisals (PPAs) are systematic assessments of built restoration projects, which provide feedback on performance of restoration approaches to improve future restoration efforts. Unfortunately, most restoration projects are not subject to systematic assessment because of lack of institutional arrangements to sustain long‐term evaluation and the orientation of most funding agencies towards project implementation rather than “studies.” As semester‐long courses on river restoration increasingly appear in university curricula at the graduate and advanced undergraduate level, independent student research projects for such courses can provide a mechanism for building a database of PPAs (and components thereof) and providing the students with a powerful learning experience. In two UC Berkeley courses, we require independent student projects involving original field research, peer review of first drafts, instructor (and often outside) review of second drafts, and presentation of results to a public symposium. Since 1995, the revised, final papers have been added to the University of California library, where they constitute one of the largest collections of restoration‐related studies currently available for any region: over 300 restoration‐related studies, of which 80 are PPAs or components thereof. Since 2003, the papers have been posted on‐line, with 40,000 full text downloads through 2010. Some term projects have directly influenced river restoration programs, inducing changes in salmon habitat enhancement project design, documenting failure of projects based on inappropriate restoration approaches, and contributing to systematic assessments of step‐pool and compound channel designs in urban areas. Student evaluations cite the term projects as valuable learning experiences.     

The ecological niches of <Emphasis Type="Italic">Bythotrephes</Emphasis> and <Emphasis Type="Italic">Leptodora:</Emphasis> lessons for predicting long-term effects of invasion

We here exploit two large datasets on zooplankton in Norwegian lakes, spanning a wide range of geographical, physical, chemical and biological properties, to assess the ecological niches and habitats of Bythotrephes longimanus and Leptodora kindtii. The species overlapped geographically, yet co-occurred only in a limited number of lakes. Bythotrephes inhabited virtually all types of lakes, except alpine localities and productive lakes dominated by cyprinid communities where the hyaline Leptodora was most abundant. The zooplankton communities also differed in Bythotrephes and Leptodora lakes, probably both reflecting different predatory regimes, but also water quality and other lake-specific properties. We found no evidence for species being excluded by the presence of Bythotrephes, rather the diversity in general was higher in lakes with these predators present compared with those without. We found, however, a very close association between Bythotrephes and Daphnia galeata and to some extent also between Bythotrephes and D. longispina, suggesting that these species also may benefit from Bythotrephes invasion. Both Bythotrephes and Leptodora species occur naturally in this region, and knowledge about the ecological preferences and the zooplankton community composition in Bythotrephes—and Leptodora lakes will provide valuable information about the long-term effects of Bythotrephes invasion and potential interaction with of Leptodora as top invertebrate predator.     

Comparative genomics of <Emphasis Type="Italic">Lactobacillus sakei</Emphasis> with emphasis on strains from meat

Lactobacillus sakei is a lactic acid bacterium important in food microbiology mainly due to its ability to ferment and preserve meat. The genome sequence of L. sakei strain 23K has revealed specialized metabolic capacities that reflect the bacterium’s adaption to meat products, and that differentiate it from other LAB. An extensive genomic diversity analysis was conducted to elucidate the core features of the species, and to provide a better comprehension of niche adaptation of the organism. Here, we describe the genomic comparison of 18 strains of L. sakei originating mainly from processed meat against the 23K strain by comparative genome hybridization. Pulsed field gel electrophoresis was used to estimate the genome sizes of the strains, which varied from 1.880 to 2.175 Mb, and the 23K genome was among the smallest. Consequently, a large part of the genome of this strain belongs to a common gene pool invariant in this species. The majority of genes important in adaption to meat products, the ability to flexibly use meat components, and robustness during meat processing and storage were conserved, such as genes involved in nucleoside scavenging, catabolism of arginine, and the ability to cope with changing redox and oxygen levels, which is indicative of the role these genes play in niche specialization within the L. sakei species. Moreover, an additional set of sequenced L. sakei genes beyond the 23K genome was present on the microarray used, and it was demonstrated that all the strains carry remnants of or complete bacteriocin operons. The genomic divergence corresponded mainly to five regions in the 23K genome, which showed features consistent with horizontal gene transfer. Carbohydrate-fermentation profiles of the strains were evaluated in light of the CGH data, and for most substrates, the genotypes were consistent with the phenotypes. We have demonstrated a highly conserved organization of the L. sakei genomes investigated, and the 23K strain is a suitable model organism to study core features of the L. sakei species.     

Increased expression of the dyslexia candidate gene DCDC2 affects length and signaling of primary cilia in neurons

DCDC2 is one of the candidate susceptibility genes for dyslexia. It belongs to the superfamily of doublecortin domain containing proteins that bind to microtubules, and it has been shown to be involved in neuronal migration. We show that the Dcdc2 protein localizes to the primary cilium in primary rat hippocampal neurons and that it can be found within close proximity to the ciliary kinesin-2 subunit Kif3a. Overexpression of DCDC2 increases ciliary length and activates Shh signaling, whereas downregulation of Dcdc2 expression enhances Wnt signaling, consistent with a functional role in ciliary signaling. Moreover, DCDC2 overexpression in C. elegans causes an abnormal neuronal phenotype that can only be seen in ciliated neurons. Together our results suggest a potential role for DCDC2 in the structure and function of primary cilia.