An important role for Myb-MuvB and its target gene KIF23 in a mouse model of lung adenocarcinoma

The conserved Myb-MuvB (MMB) multiprotein complex has an important role in transcriptional activation of mitotic genes. MMB target genes are overexpressed in several different cancer types and their elevated expression is associated with an advanced tumor state and a poor prognosis. This suggests that MMB could contribute to tumorigenesis by mediating overexpression of mitotic genes. However, although MMB has been extensively characterized biochemically, the requirement for MMB in tumorigenesis in vivo has not been investigated. Here we demonstrate that MMB is required for tumor formation in a mouse model of lung cancer driven by oncogenic K-RAS. We also identify a requirement for the mitotic kinesin KIF23, a key target gene of MMB, in tumorigenesis. RNA interference-mediated depletion of KIF23 inhibited lung tumor formation in vivo and induced apoptosis in lung cancer cell lines. Our results suggest that inhibition of KIF23 could be a strategy for treatment of lung cancer

The origins and spread of stock-keeping: the role of cultural and environmental influences on early Neolithic animal exploitation in Europe

It has long been recognised that the proportions of Neolithic domestic animal species—cattle, pig and sheep/goat—vary from region to region, but it has hitherto been unclear how much this variability is related to cultural practices or to environmental constraints. This study uses hundreds of faunal assemblages from across Neolithic Europe to reveal the distribution of animal use between north and south, east and west. The remarkable results present us with a geography of Neolithic animal society—from the rabbit-loving Mediterranean to the beef-eaters of the north and west. They also demonstrate that the choices made by early Neolithic herders were largely determined by their environments. Cultural links appear to have played only a minor role in the species composition of early Neolithic animal societie

Animal husbandry between the Roman times and the High Middle Ages in central Europe : a biometrical analysis of cattle, sheep and pig

This paper presents a meta-analysis of biometrical data of cattle (Bos taurus), sheep (Ovis aries), and pig (Sus domesticus), with a diachronic, long-term approach (first–twelfth centuries AD) and at a large regional scale (Switzerland and adjacent areas of France), with the aim of looking at changes in animal husbandry during the transition between Roman times and the Early Middle Ages. With this in mind, a comprehensive biometrical analysis is carried out, on the basis of the log-ratio technique (or logarithmic size index — LSI). The results show an increase of the size of domesticates during the Late Roman period, as well as a long period of size decrease in the subsequent centuries. The possible reasons behind this size decrease are discussed, focusing on three factors: a genetic change, less direct control over feeding and breeding, and changing patterns of herd sex ratios. We argue that these changes should be seen as an efficient adaptation of animal husbandry strategies to broader social, economic, and political transformations

modeling the laser ablation process

This chapter focuses on the problem of modeling the laser ablation process from a geometrical point of view. The objective is to create a model capable of describing the laser incision depth based on the knowledge of the laser parameters and inputs. The discussion starts with a statement of the problem, which is defined in terms of a supervised regression. Our approach is compared with existing heuristic models for the prediction of ablation depth

Does the disturbance hypothesis explain the biomass increase in basin-wide Amazon forest plot data?

Positive aboveground biomass trends have been reported from old-growth forests across the Amazon basin and hypothesized to reflect a large-scale response to exterior forcing. The result could, however, be an artefact due to a sampling bias induced by the nature of forest growth dynamics. Here, we characterize statistically the disturbance process in Amazon old-growth forests as recorded in 135 forest plots of the RAINFOR network up to 2006, and other independent research programmes, and explore the consequences of sampling artefacts using a data-based stochastic simulator. Over the observed range of annual aboveground biomass losses, standard statistical tests show that the distribution of biomass losses through mortality follow an exponential or near-identical Weibull probability distribution and not a power law as assumed by others. The simulator was parameterized using both an exponential disturbance probability distribution as well as a mixed exponential–power law distribution to account for potential large-scale blowdown events. In both cases, sampling biases turn out to be too small to explain the gains detected by the extended RAINFOR plot network. This result lends further support to the notion that currently observed biomass gains for intact forests across the Amazon are actually occurring over large scales at the current time, presumably as a response to climate change

MicroMotility: State of the art, recent accomplishments and perspectives on the mathematical modeling of bio-motility at microscopic scales

Mathematical modeling and quantitative study of biological motility (in particular, of motility at microscopic scales) is producing new biophysical insight and is offering opportunities for new discoveries at the level of both fundamental science and technology. These range from the explanation of how complex behavior at the level of a single organism emerges from body architecture, to the understanding of collective phenomena in groups of organisms and tissues, and of how these forms of swarm intelligence can be controlled and harnessed in engineering applications, to the elucidation of processes of fundamental biological relevance at the cellular and sub-cellular level. In this paper, some of the most exciting new developments in the fields of locomotion of unicellular organisms, of soft adhesive locomotion across scales, of the study of pore translocation properties of knotted DNA, of the development of synthetic active solid sheets, of the mechanics of the unjamming transition in dense cell collectives, of the mechanics of cell sheet folding in volvocalean algae, and of the self-propulsion of topological defects in active matter are discussed. For each of these topics, we provide a brief state of the art, an example of recent achievements, and some directions for future research

Disruption of Lateral Efferent Pathways: Functional Changes in Auditory Evoked Responses

The functional consequences of selectively lesioning the lateral olivocochlear efferent system in guinea pigs were studied. The lateral superior olive (LSO) contains the cell bodies of lateral olivocochlear neurons. Melittin, a cytotoxic chemical, was injected into the brain stem using stereotaxic coordinates and near-field evoked potentials to target the LSO. Brain stem histology revealed discrete damage to the LSO following the injections. Functional consequences of this damage were reflected in depressed amplitude of the compound action potential of the eighth nerve (CAP) following the lesion. Threshold sensitivity and N1 latencies were relatively unchanged. Onset adaptation of the cubic distortion product otoacoustic emission (DPOAE) was evident, suggesting a reasonably intact medial efferent system. The present results provide the first report of functional changes induced by isolated manipulation of the lateral efferent pathway. They also confirm the suggestion that changes in single-unit auditory nerve activity after cutting the olivocochlear bundle are probably a consequence of disrupting the more lateral of the two olivocochlear efferent pathways.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41379/1/10162_2002_Article_3018.pd