A Genome-wide gene-expression analysis and database in transgenic mice during development of amyloid or tau pathology

We provide microarray data comparing genome-wide differential expression and pathology throughout life in four lines of "amyloid" transgenic mice (mutant human APP, PSEN1, or APP/PSEN1) and "TAU" transgenic mice (mutant human MAPT gene). Microarray data were validated by qPCR and by comparison to human studies, including genome-wide association study (GWAS) hits. Immune gene expression correlated tightly with plaques whereas synaptic genes correlated negatively with neurofibrillary tangles. Network analysis of immune gene modules revealed six hub genes in hippocampus of amyloid mice, four in common with cortex. The hippocampal network in TAU mice was similar except that Trem2 had hub status only in amyloid mice. The cortical network of TAU mice was entirely different with more hub genes and few in common with the other networks, suggesting reasons for specificity of cortical dysfunction in FTDP17. This Resource opens up many areas for investigation. All data are available and searchable at http://www.mouseac.org

New records of marine invertebrates from Ascension Island (central Atlantic)

The sea anemone Telmatactis forskalii, the zoanthid Isaurus tuberculatus, the nemertine Baseodiscus delineatus, the echinoderms Ophiocoma wendtii and Mithrodia clavigera, the molluscs Colubraria canariensis, Glyphepithema turtoni, Tonna pennata, Trivia candidula, Melanella eburnea, Melanella n.sp., Echineulima leucophaes, Stylocheilus striatus, Limaria hians, Pteria hirundo and Callistoctopus macropus, and the crustaceans Tetraclitella sp., Oxynaspis celata, Thor amboinensis and Parribacus antarcticus are recorded from Ascension Island for the first time. A new depth record is given for the sea anemone Telmatactis cricoides. An undescribed shrimp species of the genus Lysmata and the shrimp Lysmata moorei were observed to clean fish at night

Dynamics of DNA replication loops reveal temporal control of lagging-strand synthesis

In all organisms, the protein machinery responsible for the replication of DNA, the replisome, is faced with a directionality problem. The antiparallel nature of duplex DNA permits the leading-strand polymerase to advance in a continuous fashion, but forces the lagging-strand polymerase to synthesize in the opposite direction. By extending RNA primers, the lagging-strand polymerase restarts at short intervals and produces Okazaki fragments. At least in prokaryotic systems, this directionality problem is solved by the formation of a loop in the lagging strand of the replication fork to reorient the lagging-strand DNA polymerase so that it advances in parallel with the leading-strand polymerase. The replication loop grows and shrinks during each cycle of Okazaki fragment synthesis. Here we use single-molecule techniques to visualize, in real time, the formation and release of replication loops by individual replisomes of bacteriophage T7 supporting coordinated DNA replication. Analysis of the distributions of loop sizes and lag times between loops reveals that initiation of primer synthesis and the completion of an Okazaki fragment each serve as a trigger for loop release. The presence of two triggers may represent a fail-safe mechanism ensuring the timely reset of the replisome after the synthesis of every Okazaki fragment.

Marine turtle harvest in a mixed small-scale fishery: Evidence for revised management measures

Copyright © 2013 Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in Ocean and Coastal Management. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Ocean and Coastal Management, 2013, Vol. 82, pp. 34 – 42 DOI: http://dx.doi.org/10.1016/j.ocecoaman.2013.05.004Small-scale fisheries (SSF) account for around half of the world's marine and inland fisheries, but their impact on the marine environment is usually under-estimated owing to difficulties in monitoring and regulation. Successful management of mixed SSF requires holistic approaches that sustainably exploit target species, consider non-target species and maintain fisher livelihoods. For two years, we studied the marine turtle fishery in the Turks and Caicos Islands (TCI) in the Wider Caribbean Region, where the main export fisheries are queen conch (Strombus gigas) and the spiny lobster (Panulirus argus); with fin-fish, green turtles (Chelonia mydas) and hawksbill turtles (Eretmochelys imbricata) taken for domestic consumption. We evaluate the turtle harvest in relation to the other fisheries and recommend legislation and management alternatives. We demonstrate the connectivity between multi-species fisheries and artisanal turtle capture: with increasing lobster catch-per-unit-effort (CPUE), hawksbill catch increased whilst green turtle catch decreased. With increasing conch CPUE, hawksbill catch declined and there was no demonstrable effect on green turtle catch. We estimate 176–324 green and 114–277 hawksbill turtles are harvested annually in TCI: the largest documented legal hawksbill fishery in the western Atlantic. Of particular concern is the capture of adult turtles. Current legislation focuses take on larger individuals that are key to population maintenance. Considering these data we recommend the introduction of maximum size limits for both species and a closed season on hawksbill take during the lobster fishing season. Our results highlight the need to manage turtles as part of a broader approach to SSF management

Risk factors for ulnar nerve compression at the elbow: a case control study

Background. Ulnar nerve compression at the elbow is frequently encountered as the second most common compression neuropathy in the arm. As dexterity may be severely affected, the disease entity can seriously interfere with daily life and work. However, epidemiological research considering the risk factors is rarely performed

Changes in climate extremes, fresh water availability and vulnerability to food insecurity projected at 1.5°C and 2°C global warming with a higher-resolution global climate model

This is the final version. Available on open access from the Royal Society via the DOI in this recordData accessibility: This article has no additional data.We projected changes in weather extremes, hydrological impacts and vulnerability to food insecurity at global warming of 1.5°C and 2°C relative to pre-industrial, using a new global atmospheric general circulation model HadGEM3A-GA3.0 driven by patterns of sea-surface temperatures and sea ice from selected members of the 5th Coupled Model Intercomparison Project (CMIP5) ensemble, forced with the RCP8.5 concentration scenario. To provide more detailed representations of climate processes and impacts, the spatial resolution was N216 (approx. 60 km grid length in mid-latitudes), a higher resolution than the CMIP5 models. We used a set of impacts-relevant indices and a global land surface model to examine the projected changes in weather extremes and their implications for freshwater availability and vulnerability to food insecurity. Uncertainties in regional climate responses are assessed, examining ranges of outcomes in impacts to inform risk assessments. Despite some degree of inconsistency between components of the study due to the need to correct for systematic biases in some aspects, the outcomes from different ensemble members could be compared for several different indicators. The projections for weather extremes indices and biophysical impacts quantities support expectations that the magnitude of change is generally larger for 2°C global warming than 1.5°C. Hot extremes become even hotter, with increases being more intense than seen in CMIP5 projections. Precipitation-related extremes show more geographical variation with some increases and some decreases in both heavy precipitation and drought. There are substantial regional uncertainties in hydrological impacts at local scales due to different climate models producing different outcomes. Nevertheless, hydrological impacts generally point towards wetter conditions on average, with increased mean river flows, longer heavy rainfall events, particularly in South and East Asia with the most extreme projections suggesting more than a doubling of flows in the Ganges at 2°C global warming. Some areas are projected to experience shorter meteorological drought events and less severe low flows, although longer droughts and/or decreases in low flows are projected in many other areas, particularly southern Africa and South America. Flows in the Amazon are projected to decline by up to 25%. Increases in either heavy rainfall or drought events imply increased vulnerability to food insecurity, but if global warming is limited to 1.5°C, this vulnerability is projected to remain smaller than at 2°C global warming in approximately 76% of developing countries. At 2°C, four countries are projected to reach unprecedented levels of vulnerability to food insecurity. This article is part of the theme issue 'The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'.European Union FP7Joint UK BEIS/Defra Met Office Hadley Centre Climate Programm

Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair.

Repair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification via homology directed repair (HDR) from donor DNA. Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away from other repair outcomes. Here, we utilize a pooled CRISPR screen to define host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor). We find that the Fanconi Anemia (FA) pathway is required for dsDonor HDR and that other genes act to repress HDR. Small molecule inhibition of one of these repressors, CDC7, by XL413 and other inhibitors increases the efficiency of HDR by up to 3.5 fold in many contexts, including primary T cells. XL413 stimulates HDR during a reversible slowing of S-phase that is unexplored for Cas9-induced HDR. We anticipate that XL413 and other such rationally developed inhibitors will be useful tools for gene modification

Microservice Transition and its Granularity Problem: A Systematic Mapping Study

Microservices have gained wide recognition and acceptance in software industries as an emerging architectural style for autonomic, scalable, and more reliable computing. The transition to microservices has been highly motivated by the need for better alignment of technical design decisions with improving value potentials of architectures. Despite microservices' popularity, research still lacks disciplined understanding of transition and consensus on the principles and activities underlying "micro-ing" architectures. In this paper, we report on a systematic mapping study that consolidates various views, approaches and activities that commonly assist in the transition to microservices. The study aims to provide a better understanding of the transition; it also contributes a working definition of the transition and technical activities underlying it. We term the transition and technical activities leading to microservice architectures as microservitization. We then shed light on a fundamental problem of microservitization: microservice granularity and reasoning about its adaptation as first-class entities. This study reviews state-of-the-art and -practice related to reasoning about microservice granularity; it reviews modelling approaches, aspects considered, guidelines and processes used to reason about microservice granularity. This study identifies opportunities for future research and development related to reasoning about microservice granularity.Comment: 36 pages including references, 6 figures, and 3 table

Does physical activity counselling enhance the effects of a pedometer-based intervention over the long-term : 12-month findings from the Walking for Wellbeing in the West study

Peer reviewedPublisher PD