DNA DSB repair pathway choice: an orchestrated handover mechanism

DNA double strand breaks (DSBs) are potential lethal lesions but can also lead to chromosome rearrangements, a step promoting carcinogenesis. DNA non-homologous end-joining (NHEJ) is the major DSB rejoining process and occurs in all cell cycle stages. Homologous recombination (HR) can additionally function to repair irradiation-induced two-ended DSBs in G2 phase. In mammalian cells, HR predominantly uses a sister chromatid as a template for DSB repair; thus HR functions only in late S/G2 phase. Here, we review current insight into the interplay between HR and NHEJ in G2 phase. We argue that NHEJ represents the first choice pathway, repairing approximately 80% of X-ray-induced DSBs with rapid kinetics. However, a subset of DSBs undergoes end resection and repair by HR. 53BP1 restricts resection, thereby promoting NHEJ. During the switch fromNHEJ to HR, 53BP1 is repositioned to the periphery of enlarged irradiation-induced foci (IRIF) via a BRCA1-dependent process. K63-linked ubiquitin chains, which also form at IRIF, are also repositioned as well as receptor-associated protein 80 (RAP80), a ubiquitin binding protein. RAP80 repositioning requires POH1, a proteasome component. Thus, the interfacing barriers to HR, 53BP1 and RAP80 are relieved by POH1 and BRCA1, respectively. Removal of RAP80 from the IRIF core is required for loss of the ubiquitin chains and 53BP1, and for efficient replication protein A foci formation. We propose that NHEJ is used preferentially to HR because it is a compact process that does not necessitate extensive chromatin changes in the DSB vicinity

A novel laboratory scale method for studying heat treatment of cake flour

A lab-scale method for replicating the time–temperature history experienced by cake flours undergoing heat treatment was developed based on a packed bed configuration. The performance of heat-treated flours was compared with untreated and commercially heat-treated flour by test baking a high ratio cake formulation. Both cake volume and AACC shape measures were optimal after 15 min treatment at 130 °C, though their values varied between harvests. Separate oscillatory rheometry tests of cake batter at 80–100 °C exhibited similar behaviour to the baking tests. The gel strength parameter in the weak gel model, measured at 100 °C, was shown to correlate with flour quality and was identified as a possible alternative to test baking as a means of assessing flour quality after heat treatment.A CASE Ph.D. Studentship for AKSC from the Food Processing Faraday and support from Premier Foods are all gratefully acknowledged.This is the accepted manuscript version. The final version is available from Elsevier at http://www.sciencedirect.com/science/article/pii/S0260877414003112

Tannin Acyl Hydrolase Production by Citrobacter sp. isolated from Tannin rich Environment, using Tamarindus indica seed powder

Bacterial isolate, Citrobacter sp., from tannery effluent loaded sites has proved as a potent producer of tannase. Production of tannase was compared in solid-state and submerged fermentation using tamarindseed as sole carbon source. Two times increase in tannase activity was seen in solid-state fermentation (90 U) than submerged fermentation (50 U) at 48 h from 5 g substrate

Temperature is a poor proxy for synergistic climate forcing of plankton evolution

This is the author accepted manuscript. The final version is available from The Royal Society via the DOI in this record.Abundance data available in Figshare via the link in this record.Changes in biodiversity at all levels from molecules to ecosystems are often linked to climate change, which is widely represented univariately by temperature. A global environmental driving mechanism of biodiversity dynamics is thus implied by the strong correlation between temperature proxies and diversity patterns in a wide variety of fauna and flora. Yet climate consists of many interacting variables. Species likely respond to the entire climate system as opposed to its individual facets. Here, we examine ecological and morphological traits of 12,629 individuals of two species of planktonic foraminifera with similar ecologies but contrasting evolutionary outcomes. Our results show that morphological and ecological changes are correlated to the interactions between multiple environmental factors. Models including interactions between climate variables explain at least twice as much variation in size, shape and abundance changes as models assuming that climate parameters operate independently. No dominant climatic driver can be identified: temperature alone explains remarkably little variation through our highly resolved temporal sequences, implying that a multivariate approach is required to understand evolutionary response to abiotic forcing. Our results caution against the use of a ‘silver bullet’ environmental parameter to represent global climate while studying evolutionary responses to abiotic change, and show that more comprehensive reconstruction of paleobiological dynamics requires multiple biotic and abiotic dimensions.NERC Advanced Research Fellowship NE/J018163/1Royal Society Wolfson Research Merit Awar

Understanding and optimising an identification/brief advice (IBA) service about alcohol in the community pharmacy setting

This is the final report of an evaluation into the identification/brief advice (IBA) service about alcohol in community pharmacy settings in the North West of England. Since 2007, almost 100 pharmacies in the North West have - at some point - been commissioned to provide an identification and brief advice (IBA) service for alcohol. This evaluation sought to understand how the service had been adapted for and implemented in the community pharmacy setting, and how its potential might be maximised. Its aims were: 1. To characterise, consolidate and optimise both the constant and variable elements of the pharmacy alcohol identification/brief advice (IBA) service in NHS Northwest, and 2. To inform planning for current and future pharmacy based services promoting safe consumption of alcohol. The evaluation was split into three main workstreams, supported by a preliminary scoping phase, and combined quantitative and qualitative methods: • Descriptive and comparative statistical analysis of pharmacy alcohol IBA data; • In-pharmacy work, including observation of staff engagement with customers, recording consultations between staff and customers, follow-up telephone interviews with customers, and group feedback interviews with pharmacy staff; • Stakeholder engagement through self-completion surveys, semi-structured interviews and a workshop. This report gives the background to the project, and details the methods, results and implications

Complementarity of Spike- and Rate-Based Dynamics of Neural Systems

Relationships between spiking-neuron and rate-based approaches to the dynamics of neural assemblies are explored by analyzing a model system that can be treated by both methods, with the rate-based method further averaged over multiple neurons to give a neural-field approach. The system consists of a chain of neurons, each with simple spiking dynamics that has a known rate-based equivalent. The neurons are linked by propagating activity that is described in terms of a spatial interaction strength with temporal delays that reflect distances between neurons; feedback via a separate delay loop is also included because such loops also exist in real brains. These interactions are described using a spatiotemporal coupling function that can carry either spikes or rates to provide coupling between neurons. Numerical simulation of corresponding spike- and rate-based methods with these compatible couplings then allows direct comparison between the dynamics arising from these approaches. The rate-based dynamics can reproduce two different forms of oscillation that are present in the spike-based model: spiking rates of individual neurons and network-induced modulations of spiking rate that occur if network interactions are sufficiently strong. Depending on conditions either mode of oscillation can dominate the spike-based dynamics and in some situations, particularly when the ratio of the frequencies of these two modes is integer or half-integer, the two can both be present and interact with each other

Extracting a Detailed Magnetostratigraphy From Weakly Magnetized, Oligocene to Early Miocene Sediment Drifts Recovered at IODP Site U1406 (Newfoundland Margin, Northwest Atlantic Ocean)

Fine‐grained magnetic particles in deep‐sea sediments often statistically align with the ambient magnetic field during (and shortly after) deposition and can therefore record geomagnetic reversals. Correlation of these reversals to a geomagnetic polarity time scale is an important geochronological tool that facilitates precise stratigraphic correlation and dating of geological records globally. Sediments often carry a remanence strong enough for confident identification of polarity reversals, but in some cases a low signal‐to‐noise ratio prevents the construction of a reliable and robust magnetostratigraphy. Here we implement a data‐filtering protocol, which can be integrated with the UPmag software package, to automatically reduce the maximum angular deviation and statistically mask noisy data and outliers deemed unsuitable for magnetostratigraphic interpretation. This protocol thus extracts a clearer signal from weakly magnetized sediments recovered at Integrated Ocean Drilling Program (IODP) Expedition 342 Site U1406 (Newfoundland margin, northwest Atlantic Ocean). The resulting magnetostratigraphy, in combination with shipboard and shore‐based biostratigraphy, provides an age model for the study interval from IODP Site U1406 between Chrons C6Ar and C9n (∼21–27 Ma). We identify rarely observed geomagnetic directional changes within Chrons C6Br, C7r, and C7Ar, and perhaps within Subchron C8n.1n. Our magnetostratigraphy dates three intervals of unusual stratigraphic behavior within the sediment drifts at IODP Site U1406 on the Newfoundland margin. These lithostratigraphic changes are broadly concurrent with the coldest climatic phases of the middle Oligocene to early Miocene and we hypothesize that they reflect changes in bottom water circulation

Response to “Comment to “The transition on North America from the warm humid Pliocene to the glaciated Quaternary traced by eolian dust deposition at a benchmark North Atlantic Ocean drill site, by David Lang et al. Quaternary Science Reviews 93: 125-141””

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Coccolithophore calcification response to past ocean acidification and climate change

Anthropogenic carbon dioxide emissions are forcing rapid ocean chemistry changes and causing ocean acidification (OA), which is of particular significance for calcifying organisms, including planktonic coccolithophores. Detailed analysis of coccolithophore skeletons enables comparison of calcite production in modern and fossil cells in order to investigate biomineralization response of ancient coccolithophores to climate change. Here we show that the two dominant coccolithophore taxa across the Paleocene–Eocene Thermal Maximum (PETM) OA global warming event (~56 million years ago) exhibited morphological response to environmental change and both showed reduced calcification rates. However, only Coccolithus pelagicus exhibits a transient thinning of coccoliths, immediately before the PETM, that may have been OA-induced. Changing coccolith thickness may affect calcite production more significantly in the dominant modern species Emiliania huxleyi, but, overall, these PETM records indicate that the environmental factors that govern taxonomic composition and growth rate will most strongly influence coccolithophore calcification response to anthropogenic change

Categorical dilemmas: challenges for HIV prevention among men who have sex with men and transgender women in Vietnam

In Vietnam, HIV continues disproportionately to affect men who have sex with men and transgender women, and the increase in HIV prevalence in these populations may be related to a lack of tailoring of current prevention approaches, which often fail to address social diversity within these populations. To effectively respond to HIV in Vietnam, it is imperative to identify sub-populations within the broad category of ‘men who have sex with men’ (MSM), a term which in Vietnam as in many other sites frequently subsumes transgender women. In this paper, we document the different categories used to describe people who engage in same-sex sexual practices and/or non-normative gender performances drawing on data collected via in-depth interviews and focus groups with a total of 79 participants in Hanoi. We identified over 40 different categories used to describe men who have sex with men and/or transgender women. These categories could be described as behaviourally-based, identity-based, or emic, and each carried different meanings, uses (based on age and geography) and levels of stigma. The categories shine light on the complexity of identities among men who have sex with men and transgender women and have utility for future research and programming to more comprehensively address HIV in Vietnam