A resource for large-scale RNA-interference-based screens in mammals

Gene silencing by RNA interference (RNAi) in mammalian cells using small interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) has become a valuable genetic tool. Here, we report the construction and application of a shRNA expression library targeting 9,610 human and 5,563 mouse genes. This library is presently composed of about 28,000 sequence-verified shRNA expression cassettes contained within multi-functional vectors, which permit shRNA cassettes to be packaged in retroviruses, tracked in mixed cell populations by means of DNA 'bar codes', and shuttled to customized vectors by bacterial mating. In order to validate the library, we used a genetic screen designed to report defects in human proteasome function. Our results suggest that our large-scale RNAi library can be used in specific, genetic applications in mammals, and will become a valuable resource for gene analysis and discovery.     

Further geological and palaeoanthropological investigations at the Maludong hominin site, Yunnan Province, Southwest China

Three-dimensional mapping and section work undertaken by us in 2008 have identified 11 stratigraphic units at Maludong site. AMS radiocarbon dating of charcoal established an accurate and internally consistent age profile for the sequence of 17.8±0.2 ka to 13.2±0.1 ka. Archaeomagnetic analysis showed changes in externally derived pedogenically enhanced material consistent with a warming in climate between the cold period of Henrich Event 1 and the Blling-AllerCd interstadial. Human remains recovered during the 1989 excavation were derived from a deposit dating to this interstadial, or between 14.3±0.3 ka and 13.5±0.1 ka. An- thropogenic features, including burnt rocks, baked sediment and thick charcoal and ash layers, were identified and examined through archaeomagnetic analysis. Two monkey fossils are described here, one of them being reassigned from Macaca robustus to M. aft＇. M. assamensis. They confirm the young age of the site and also show signs of anthropogenic alteration in the form of burning. Additional human cranial remains are reported for the first time and new data are provided for some specimens described previously. A range of new features is identified that strengthen the affinities of the Maludong remains to archaic humans. The presence of this globally unique mosaic of archaic and modern features raises important questions about human evolutionary his- tory in East Asia during the Late Upper Pleistocene.     

Comparison of prospective Hawkes and recursive point process models for Ebola in DRC

Point process models, such as Hawkes and recursive models, have recently been shown to offer improved accuracy over more traditional compartmental models for the purposes of modeling and forecasting the spread of disease epidemics. To explicitly test the performance of these two models in a real-world and ongoing epidemic, we compared the fit of Hawkes and recursive models to outbreak data on Ebola virus disease (EVD) in the Democratic Republic of the Congo in 2018–2020. The models were estimated, and the forecasts were produced, time-stamped, and stored in real time, so that their prospective value can be assessed and to guard against potential overfitting. The fit of the two models was similar, with both models resulting in much smaller errors in the beginning and waning phases of the epidemic and with slightly smaller error sizes on average for the Hawkes model compared with the recursive model. Our results suggest that both Hawkes and recursive point process models can be used in near real time during the course of an epidemic to help predict future cases and inform management and mitigation strategies.     

Wave acceleration of electrons in the Van Allen radiation belts

The Van Allen radiation belts are two regions encircling the Earth in which energetic charged particles are trapped inside the Earth's magnetic field. Their properties vary according to solar activity and they represent a hazard to satellites and humans in space. An important challenge has been to explain how the charged particles within these belts are accelerated to very high energies of several million electron volts. Here we show, on the basis of the analysis of a rare event where the outer radiation belt was depleted and then re-formed closer to the Earth, that the long established theory of acceleration by radial diffusion is inadequate; the electrons are accelerated more effectively by electromagnetic waves at frequencies of a few kilohertz. Wave acceleration can increase the electron flux by more than three orders of magnitude over the observed timescale of one to two days, more than sufficient to explain the new radiation belt. Wave acceleration could also be important for Jupiter, Saturn and other astrophysical objects with magnetic fields.     

Mouse prepro-epidermal growth factor synthesis by the kidney and other tissues

Epidermal growth factor (EGF), a protein comprising 53 amino acids, is derived from a precursor of 1,217 amino acids that includes at least seven EGF-like sequences. EGF has diverse biological activities: it is a potent mitogen for many tissue culture cells, inhibits gastric acid secretion from the intestinal mucosa and promotes healing of the corneal epithelium. EGF given to fetal animals accelerates several developmental processes including palate formation, incisor eruption, eyelid opening and lung maturation. However, the physiological roles of EGF in vivo are unknown. The presence of high-affinity receptors in many fetal and adult tissues suggests that EGF is involved in normal cellular functions. Immunocytochemical studies have revealed the presence of EGF in mouse and human submaxillary glands, rat brain and human intestine. The low levels of EGF in extracts from many tissues may reflect sequestration rather than synthesis of the polypeptide. We show here that several mouse tissues contain preproEGF mRNA and that it is synthesized mainly in the distal tubules of the kidney. PreproEGF does not seem to be processed to EGF or other peptides in this tissue.     

Interlevel Dynamics in Systemic Action Research

Levels of analysis are commonly used as frameworks for researching, understanding, and intervening in organizational systems. Levels of analysis typically refer to the identification of issues at units of complexity, such as the individual, the group, the intergroup, and the organization. The construct of levels of analysis is traditionally an important dimension of action research. This article reviews the traditional use of levels of analysis as the focus of action research and extends the notion to levels of aggregation or interlevel dynamics. It illustrates how interlevel dynamics are important both as the focus of action research and to the action research process itself.     

Developing Managers as Healing Agents in Organizations: A Co-Operative Inquiry Approach

This action research examines how a health service manager, with a clinical background, sought to develop his clinical skills in a management context. When asked to undertake an evaluation of an addiction counseling service, he found that there was evidence of systemic ill-health expressed through feelings of powerlessness, hurt, and alienation among the staff of the service. The article describes how the manager used action research, and in particular co-operative inquiry, to become an agent of healing in his own place of work. It illustrates how the co-operative inquiry process can be used to help individuals or groups to overcome feelings of alienation and powerlessness in organizations. By dealing with these feelings through a process of co-operative inquiry the conditions necessary to improve systemic health can be created to help develop a service and meet service objectives It explores the neglected subject of how managers can be agents of healing in organizations.