4,253 research outputs found

    A newly identified prophage-encoded gene, <i>ymfM</i>, causes SOS-inducible filamentation in <i>Escherichia coli</i>.

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    Rod-shaped bacteria such as Escherichia coli can regulate cell division in response to stress, leading to filamentation, a process where cell growth and DNA replication continues in the absence of division, resulting in elongated cells. The classic example of stress is DNA damage which results in the activation of the SOS response. While the inhibition of cell division during SOS has traditionally been attributed to SulA in E. coli, a previous report suggests that the e14 prophage may also encode an SOS-inducible cell division inhibitor, previously named SfiC. However, the exact gene responsible for this division inhibition has remained unknown for over 35 years. A recent high-throughput over-expression screen in E. coli identified the e14 prophage gene, ymfM, as a potential cell division inhibitor. In this study, we show that the inducible expression of ymfM from a plasmid causes filamentation. We show that this expression of ymfM results in the inhibition of Z ring formation and is independent of the well characterised inhibitors of FtsZ ring assembly in E. coli, SulA, SlmA and MinC. We confirm that ymfM is the gene responsible for the SfiC phenotype as it contributes to the filamentation observed during the SOS response. This function is independent of SulA, highlighting that multiple alternative division inhibition pathways exist during the SOS response. Our data also highlight that our current understanding of cell division regulation during the SOS response is incomplete and raises many questions regarding how many inhibitors there actually are and their purpose for the survival of the organism.Importance:Filamentation is an important biological mechanism which aids in the survival, pathogenesis and antibiotic resistance of bacteria within different environments, including pathogenic bacteria such as uropathogenic Escherichia coli Here we have identified a bacteriophage-encoded cell division inhibitor which contributes to the filamentation that occurs during the SOS response. Our work highlights that there are multiple pathways that inhibit cell division during stress. Identifying and characterising these pathways is a critical step in understanding survival tactics of bacteria which become important when combating the development of bacterial resistance to antibiotics and their pathogenicity

    Conceptualizing cultures of violence and cultural change

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    The historiography of violence has undergone a distinct cultural turn as attention has shifted from examining violence as a clearly defined (and countable) social problem to analysing its historically defined 'social meaning'. Nevertheless, the precise nature of the relationship between 'violence' and 'culture' is still being established. How are 'cultures of violence' formed? What impact do they have on violent behaviour? How do they change? This essay examines some of the conceptual aspects of the relationship between culture and violence. It brings together empirical research into nineteenth-century England with recent research results from other European contexts to examine three aspects of the relationship between culture and violence. These are organised under the labels 'seeing violence', 'identifying the violent' and 'changing violence'. Within a particular society, narratives regarding particular kinds of behaviour shape cultural attitudes. The notion 'violence' is thus defined in relation to physically aggressive acts as well as by being connected to other kinds of attitudes and contexts. As a result, the boundaries between physical aggression which is legitimate and that which is illegitimate (and thus 'violence') are set. Once 'violence' is defined, particular cultures form ideas about who is responsible for it: reactions to violence become associated with social arrangements such as class and gender as well as to attitudes toward the self. Finally, cultures of violence make efforts to tame or eradicate illegitimate forms of physical aggression. This process is not only connected to the development of new forms of power (e.g., new policing or punishment strategies) but also to less tangible cultural influences which aim at changing the behaviour defined as violence (in particular among the social groups identified as violent). Even if successful, this three-tiered process of seeing violence, identifying the violent and changing violence continues anew, emphasising the ways that cultures of violence develop through a continuous process of reevaluation and reinvention

    Structural and functional characterisation of human RNA helicase DHX8 provides insights into the mechanism of RNA-stimulated ADP release.

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    DHX8 is a crucial DEAH-box RNA helicase involved in splicing and required for the release of mature mRNA from the spliceosome. Here, we report the biochemical characterisation of full-length human DHX8 and the catalytically active helicase core DHX8Δ547, alongside crystal structures of DHX8Δ547 bound to ADP and a structure of DHX8Δ547 bound to poly(A)6 single-strand RNA. Our results reveal that DHX8 has an in vitro binding preference for adenine-rich RNA and that RNA binding triggers the release of ADP through significant conformational flexibility in the conserved DEAH-, P-loop and hook-turn motifs. We demonstrate the importance of R620 and both the hook-turn and hook-loop regions for DHX8 helicase activity and propose that the hook-turn acts as a gatekeeper to regulate the directional movement of the 3' end of RNA through the RNA-binding channel. This study provides an in-depth understanding of the activity of DHX8 and contributes insights into the RNA-unwinding mechanisms of the DEAH-box helicase family

    A Universal Model of Global Civil Unrest

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    Civil unrest is a powerful form of collective human dynamics, which has led to major transitions of societies in modern history. The study of collective human dynamics, including collective aggression, has been the focus of much discussion in the context of modeling and identification of universal patterns of behavior. In contrast, the possibility that civil unrest activities, across countries and over long time periods, are governed by universal mechanisms has not been explored. Here, we analyze records of civil unrest of 170 countries during the period 1919-2008. We demonstrate that the distributions of the number of unrest events per year are robustly reproduced by a nonlinear, spatially extended dynamical model, which reflects the spread of civil disorder between geographic regions connected through social and communication networks. The results also expose the similarity between global social instability and the dynamics of natural hazards and epidemics.Comment: 8 pages, 3 figure

    Coherent spinor dynamics in a spin-1 Bose condensate

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    Collisions in a thermal gas are perceived as random or incoherent as a consequence of the large numbers of initial and final quantum states accessible to the system. In a quantum gas, e.g. a Bose-Einstein condensate or a degenerate Fermi gas, the phase space accessible to low energy collisions is so restricted that collisions be-come coherent and reversible. Here, we report the observation of coherent spin-changing collisions in a gas of spin-1 bosons. Starting with condensates occupying two spin states, a condensate in the third spin state is coherently and reversibly created by atomic collisions. The observed dynamics are analogous to Josephson oscillations in weakly connected superconductors and represent a type of matter-wave four-wave mixing. The spin-dependent scattering length is determined from these oscillations to be -1.45(18) Bohr. Finally, we demonstrate coherent control of the evolution of the system by applying differential phase shifts to the spin states using magnetic fields.Comment: 19 pages, 3 figure

    DETERMINATION OF THE THERMODYNAMIC PARAMETERS FOR TRANSFER OF ALKOXYPHENOLS FROM AQUEOUS-SOLUTION TO SDS MICELLES BY A TAYLOR-ARIS DIFFUSION TECHNIQUE

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    Using Taylor-Aris diffusion techniques, thermodynamic parameters have been measured for the transfer of a series of alkoxyphenols from water into SDS micelles. The results are compared with those for transfer to bulk organic solvents and to cells of Escherichia coli. The SDS micelles are found to be marginally more polar than n-octanol, but the results reveal significant differences between bulk solvents and the more ordered micellar pseudophase.87172741274

    Elevated arousal at time of decision-making is not the arbiter of risk avoidance in chickens

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    The somatic marker hypothesis proposes that humans recall previously experienced physiological responses to aid decision-making under uncertainty. However, little is known about the mechanisms used by non-human animals to integrate risk perception with predicted gains and losses. We monitored the behaviour and physiology of chickens when the choice between a high-gain (large food quantity), high-risk (1 in 4 probability of receiving an air-puff) option (HGRAP) or a low-gain (small food quantity), no-risk (of an air-puff) (LGNAP) option. We assessed when arousal increased by considering different stages of the decision-making process (baseline, viewing, anticipation, reward periods) and investigated whether autonomic responses influenced choice outcome both immediately and in the subsequent trial. Chickens were faster to choose and their heart-rate significantly increased between the viewing and anticipation (post-decision, pre-outcome) periods when selecting the HGRAP option. This suggests that they responded physiologically to the impending risk. Additionally, arousal was greater following a HGRAP choice that resulted in an air-puff, but this did not deter chickens from subsequently choosing HGRAP. In contrast to human studies, we did not find evidence that somatic markers were activated during the viewing period, suggesting that arousal is not a good measure of avoidance in non-human animals

    Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

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    FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD

    Increasing confidence and changing behaviors in primary care providers engaged in genetic counselling.

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    BackgroundScreening and counseling for genetic conditions is an increasingly important part of primary care practice, particularly given the paucity of genetic counselors in the United States. However, primary care physicians (PCPs) often have an inadequate understanding of evidence-based screening; communication approaches that encourage shared decision-making; ethical, legal, and social implication (ELSI) issues related to screening for genetic mutations; and the basics of clinical genetics. This study explored whether an interactive, web-based genetics curriculum directed at PCPs in non-academic primary care settings was superior at changing practice knowledge, attitudes, and behaviors when compared to a traditional educational approach, particularly when discussing common genetic conditions.MethodsOne hundred twenty one PCPs in California and Pennsylvania physician practices were randomized to either an Intervention Group (IG) or Control Group (CG). IG physicians completed a 6 h interactive web-based curriculum covering communication skills, basics of genetic testing, risk assessment, ELSI issues and practice behaviors. CG physicians were provided with a traditional approach to Continuing Medical Education (CME) (clinical review articles) offering equivalent information.ResultsPCPs in the Intervention Group showed greater increases in knowledge compared to the Control Group. Intervention PCPs were also more satisfied with the educational materials, and more confident in their genetics knowledge and skills compared to those receiving traditional CME materials. Intervention PCPs felt that the web-based curriculum covered medical management, genetics, and ELSI issues significantly better than did the Control Group, and in comparison with traditional curricula. The Intervention Group felt the online tools offered several advantages, and engaged in better shared decision making with standardized patients, however, there was no difference in behavior change between groups with regard to increases in ELSI discussions between PCPs and patients.ConclusionWhile our intervention was deemed more enjoyable, demonstrated significant factual learning and retention, and increased shared decision making practices, there were few differences in behavior changes around ELSI discussions. Unfortunately, barriers to implementing behavior change in clinical genetics is not unique to our intervention. Perhaps the missing element is that busy physicians need systems-level support to engage in meaningful discussions around genetics issues. The next step in promoting active engagement between doctors and patients may be to put into place the tools needed for PCPs to easily access the materials they need at the point-of-care to engage in joint discussions around clinical genetics
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