Expression of soluble, active fragments of the morphogenetic protein SpoIIE from Bacillus subtilis using a library-based construct screen

SpoIIE is a dual function protein that plays important roles during sporulation in Bacillus subtilis. It binds to the tubulin-like protein FtsZ causing the cell division septum to relocate from mid-cell to the cell pole, and it dephosphorylates SpoIIAA phosphate leading to establishment of differential gene expression in the two compartments following the asymmetric septation. Its 872 residue polypeptide contains a multiple-membrane spanning sequence at the N-terminus and a PP2C phosphatase domain at the C-terminus. The central segment that binds to FtsZ is unlike domains of known structure or function, moreover the domain boundaries are poorly defined and this has hampered the expression of soluble fragments of SpoIIE at the levels required for structural studies. Here we have screened over 9000 genetic constructs of spoIIE using a random incremental truncation library approach, ESPRIT, to identify a number of soluble C-terminal fragments of SpoIIE that were aligned with the protein sequence to map putative domains and domain boundaries. The expression and purification of three fragments were optimised, yielding multimilligram quantities of the PP2C phosphatase domain, the putative FtsZ-binding domain and a larger fragment encompassing both these domains. All three fragments are monomeric and the PP2C domain-containing fragments have phosphatase activity

Bibliometrics of systematic reviews : analysis of citation rates and journal impact factors

Background: Systematic reviews are important for informing clinical practice and health policy. The aim of this study was to examine the bibliometrics of systematic reviews and to determine the amount of variance in citations predicted by the journal impact factor (JIF) alone and combined with several other characteristics. Methods: We conducted a bibliometric analysis of 1,261 systematic reviews published in 2008 and the citations to them in the Scopus database from 2008 to June 2012. Potential predictors of the citation impact of the reviews were examined using descriptive, univariate and multiple regression analysis. Results: The mean number of citations per review over four years was 26.5 (SD +/-29.9) or 6.6 citations per review per year. The mean JIF of the journals in which the reviews were published was 4.3 (SD +/-4.2). We found that 17% of the reviews accounted for 50% of the total citations and 1.6% of the reviews were not cited. The number of authors was correlated with the number of citations (r = 0.215, P =5.16) received citations in the bottom quartile (eight or fewer), whereas 9% of reviews published in the lowest JIF quartile (<=2.06) received citations in the top quartile (34 or more). Six percent of reviews in journals with no JIF were also in the first quartile of citations. Conclusions: The JIF predicted over half of the variation in citations to the systematic reviews. However, the distribution of citations was markedly skewed. Some reviews in journals with low JIFs were well-cited and others in higher JIF journals received relatively few citations; hence the JIF did not accurately represent the number of citations to individual systematic reviews

Hormonal Signal Amplification Mediates Environmental Conditions during Development and Controls an Irreversible Commitment to Adulthood

Many animals can choose between different developmental fates to maximize fitness. Despite the complexity of environmental cues and life history, different developmental fates are executed in a robust fashion. The nematode Caenorhabditis elegans serves as a powerful model to examine this phenomenon because it can adopt one of two developmental fates (adulthood or diapause) depending on environmental conditions. The steroid hormone dafachronic acid (DA) directs development to adulthood by regulating the transcriptional activity of the nuclear hormone receptor DAF-12. The known role of DA suggests that it may be the molecular mediator of environmental condition effects on the developmental fate decision, although the mechanism is yet unknown. We used a combination of physiological and molecular biology techniques to demonstrate that commitment to reproductive adult development occurs when DA levels, produced in the neuroendocrine XXX cells, exceed a threshold. Furthermore, imaging and cell ablation experiments demonstrate that the XXX cells act as a source of DA, which, upon commitment to adult development, is amplified and propagated in the epidermis in a DAF-12 dependent manner. This positive feedback loop increases DA levels and drives adult programs in the gonad and epidermis, thus conferring the irreversibility of the decision. We show that the positive feedback loop canalizes development by ensuring that sufficient amounts of DA are dispersed throughout the body and serves as a robust fate-locking mechanism to enforce an organism-wide binary decision, despite noisy and complex environmental cues. These mechanisms are not only relevant to C. elegans but may be extended to other hormonal-based decision-making mechanisms in insects and mammals

Estimating population size, density and dynamics of Pre-Pottery Neolithic villages in the central and southern Levant: an analysis of Beidha, southern Jordan

The Pre-Pottery Neolithic (PPN) of the central and southern Levant played an integral role in the Neolithic Demographic Transition (NDT) from mobile hunter-gatherer to village-based, agro-pastoralist societies. An understanding of population dynamics is essential for reconstructing the trajectories of these early village societies. However, few investigations have produced absolute estimates of population parameters for these villages and those which have base estimates on a limited methodological framework. This research examines the methodological and theoretical basis for existing estimates, and explores a range of methodologies in order to derive more empirically-robust demographic data. Results reveal that commonly utilized methodologies and population density coefficients employed for estimating PPN village populations require re-evaluation. This article presents the application of methodologies to the PPNB site of Beidha in southern Jordan

Novel HBsAg mutations correlate with hepatocellular carcinoma, hamper HBsAg secretion and promote cell proliferation in vitro

An impaired HBsAg-secretion can increase HBV oncogenic-properties. Here, we investigate genetic-determinants in HBsAg correlated with HBV-induced hepatocellular carcinoma (HCC), and their impact on HBsAg-secretion and cell-proliferation

Early invaders - Farmers, the granary weevil and other uninvited guests in the Neolithic

The Neolithic and the spread of agriculture saw several introductions of insect species associated with the environments and activities of the first farmers. Fossil insect research from the Neolithic lake settlement of Dispilio in Macedonia, northern Greece, provides evidence for the early European introduction of a flightless weevil, the granary weevil, Sitophilus granarius, which has since become cosmopolitan and one of the most important pests of stored cereals. The records of the granary weevil from the Middle Neolithic in northern Greece illuminate the significance of surplus storage for the spread of agriculture. The granary weevil and the house fly, Musca domestica were also introduced in the Neolithic of central Europe, with the expansion of Linear Band Keramik (LBK) culture groups. This paper reviews Neolithic insect introductions in Europe, including storage pests, discusses their distribution during different periods and the reasons behind the trends observed. Storage farming may be differentiated from pastoral farming on the basis of insect introductions arriving with incoming agricultural groups

Revisiting and modelling the woodland farming system of the early Neolithic Linear Pottery Culture (LBK), 5600–4900 B.C

International audienceThis article presents the conception and the conceptual results of a modelling representation of the farming systems of the Linearbandkeramik Culture (LBK). Assuming that there were permanent fields (PF) then, we suggest four ways that support the sustainability of such a farming system over time: a generalized pollarding and coppicing of trees to increase the productivity of woodland areas for foddering more livestock, which itself can then provide more manure for the fields, a generalized use of pulses grown together with cereals during the same cropping season, thereby reducing the needs for manure. Along with assumptions limiting bias on village and family organizations, the conceptual model which we propose for human environment in the LBK aims to be sustainable for long periods and can thereby overcome doubts about the PFs hypothesis for the LBK farming system. Thanks to a reconstruction of the climate of western Europe and the consequent vegetation pattern and productivity arising from it, we propose a protocol of experiments and validation procedures for both testing the PFs hypothesis and defining its eco-geographical area

Late Holocene climate: Natural or anthropogenic?

For more than a decade, scientists have argued about the warmth of the current interglaciation. Was the warmth of the preindustrial late Holocene natural in origin, the result of orbital changes that had not yet driven the system into a new glacial state? Or was it in considerable degree the result of humans intervening in the climate system through greenhouse gas emissions from early agriculture? Here we summarize new evidence that moves this debate forward by testing both hypotheses. By comparing late Holocene responses to those that occurred during previous interglaciations (in section 2), we assess whether the late Holocene responses look different (and thus anthropogenic) or similar (and thus natural). This comparison reveals anomalous (anthropogenic) signals. In section 3, we review paleoecological and archaeological syntheses that provide ground truth evidence on early anthropogenic releases of greenhouse gases. The available data document large early anthropogenic emissions consistent with the anthropogenic ice core anomalies, but more information is needed to constrain their size. A final section compares natural and anthropogenic interpretations of the δ13C trend in ice core CO2

The prevalence of non-fatal overdose among people who inject drugs:a multi-stage systematic review and meta-analysis

Background: People who inject drugs (PWID) are at an elevated risk of fatal overdose in the first year after experiencing a non-fatal event. Such non-fatal events may also result in overdose-related sequelae, ranging from physical injury to paralysis. Given variation in drug markets and treatment availability across countries and regions, we may see similar variations in non-fatal overdose prevalence. Monitoring non-fatal overdose prevalence among PWID is essential for informing treatment intervention efforts, and thus our review aims to estimate the global, regional, and national prevalence of non-fatal overdose, and determine characteristics associated with experiencing such an event.Methods: We conducted a systematic review and meta-analyses to estimate country, regional, and global estimates of recent and lifetime non-fatal overdose prevalence among PWID. Using meta-regression analyses we also determined associations between sample characteristics and non-fatal overdose prevalence.Results: An estimated 3.2 (1.8-5.2) million PWID have experienced at least one overdose in the previous year. Among PWID, 20.5% (15.0-26.1%) and 41.5% (34.6-48.4%) had experienced a non-fatal event in the previous 12 months and lifetime respectively. Frequent injecting was strongly associated with PWID reporting recent and lifetime non-fatal overdose. Estimates of recent non-fatal overdose were particularly high in Asia and North America. Conclusion: Around one in five PWID are at an elevated risk of fatally overdosing every year, however there is substantial geographical variation. In countries with higher rates of non-fatal overdose there is need to introduce or mainstream overdose prevention strategies such as opioid agonist treatment and naloxone administration training programs.<br/

The chronology of culture: a comparative assessment of European Neolithic dating approaches

Archaeologists have long sought appropriate ways to describe the duration and floruit of archaeological cultures in statistical terms. Thus far, chronological reasoning has been largely reliant on typological sequences. Using summed probability distributions, the authors here compare radiocarbon dates for a series of European Neolithic cultures with their generally accepted ‘standard’ date ranges and with the greater precision afforded by dendrochronology, where that is available. The resulting analysis gives a new and more accurate description of the duration and intensity of European Neolithic cultures