A genomic view of the NOD-like receptor family in teleost fish: identification of a novel NLR subfamily in zebrafish

<p>Abstract</p> <p>Background</p> <p>A large multigene family of NOD-like receptor (NLR) molecules have been described in mammals and implicated in immunity and apoptosis. Little information, however, exists concerning this gene family in non-mammalian taxa. This current study, therefore, provides an in-depth investigation of this gene family in lower vertebrates including extensive phylogenetic comparison of zebrafish NLRs with orthologs in tetrapods, and analysis of their tissue-specific expression.</p> <p>Results</p> <p>Three distinct NLR subfamilies were identified by mining genome databases of various non-mammalian vertebrates; the first subfamily (NLR-A) resembles mammalian NODs, the second (NLR-B) resembles mammalian NALPs, while the third (NLR-C) appears to be unique to teleost fish. In zebrafish, NLR-A and NLR-B subfamilies contain five and six genes respectively. The third subfamily is large, containing several hundred NLR-C genes, many of which are predicted to encode a C-terminal B30.2 domain. This subfamily most likely evolved from a NOD3-like molecule. Gene predictions for zebrafish NLRs were verified using sequence derived from ESTs or direct sequencing of cDNA. Reverse-transcriptase (RT)-PCR analysis confirmed expression of representative genes from each subfamily in selected tissues.</p> <p>Conclusion</p> <p>Our findings confirm the presence of multiple NLR gene orthologs, which form a large multigene family in teleostei. Although the functional significance of the three major NLR subfamilies is unclear, we speculate that conservation and abundance of NLR molecules in all teleostei genomes, reflects an essential role in cellular control, apoptosis or immunity throughout bony fish.</p

Banking from Leeds, not London: regional strategy and structure at the Yorkshire Bank, 1859–1952

Industrial philanthropist Edward Akroyd created the Yorkshire Penny Savings Bank in 1859. Despite competition from the Post Office Savings Bank after 1861 and a serious reserve problem in 1911, it sustained his overall strategy to become a successful regional bank. Using archival and contemporary sources to build on recent scholarship illustrating how savings banks were integrated into local economies and the complementary roles of philanthropy and paternalism, we analyse an English regional bank's strategy, including an assessment of strategic innovation, ownership changes and management structure. This will demonstrate that the founder's vision continued, even though the 1911 crisis radically altered both strategy and structure

Detecting genetic regions associated with height in the native ponies of the British Isles by using high density SNP genotyping

Height is an important characteristic in the equine industry, although little is known about its genetic control in native British breeds of ponies. This study aimed to map QTL data with the withers height in four pony breeds native to the British Isles, including two different sections within Welsh Cobs. In this study, a genome-wide analysis approach using the Illumina Equine SNP50 Infinium BeadChip was applied to 105 ponies and cobs. Analysis identified 222 highly significant height-associated SNPs (P < 10-5), among which three SNPs on ECA9 have also been previously reported elsewhere. The highest number of significant SNPs associated to height in the native British horses were located on ECA1, ECA8 and ECA16

The Flux-Anomaly-Forced Model Intercomparison Project (FAFMIP) contribution to CMIP6: investigation of sea-level and ocean climate change in response to CO₂ forcing

The Flux-Anomaly-Forced Model Intercomparison Project (FAFMIP) aims to investigate the spread in simulations of sea-level and ocean climate change in response to CO2 forcing by atmosphere–ocean general circulation models (AOGCMs). It is particularly motivated by the uncertainties in projections of ocean heat uptake, global-mean sea-level rise due to thermal expansion and the geographical patterns of sea-level change due to ocean density and circulation change. FAFMIP has three tier-1 experiments, in which prescribed surface flux perturbations of momentum, heat and freshwater respectively are applied to the ocean in separate AOGCM simulations. All other conditions are as in the pre-industrial control. The prescribed fields are typical of pattern and magnitude of changes in these fluxes projected by AOGCMs for doubled CO2 concentration. Five groups have tested the experimental design with existing AOGCMs. Their results show diversity in the pattern and magnitude of changes, with some common qualitative features. Heat and water flux perturbation cause the dipole in sea-level change in the North Atlantic, while momentum and heat flux perturbation cause the gradient across the Antarctic Circumpolar Current. The Atlantic meridional overturning circulation (AMOC) declines in response to the heat flux perturbation, and there is a strong positive feedback on this effect due to the consequent cooling of sea-surface temperature in the North Atlantic, which enhances the local heat input to the ocean. The momentum and water flux perturbations do not substantially affect the AMOC. Heat is taken up largely as a passive tracer in the Southern Ocean, which is the region of greatest heat input, while the weakening of the AMOC causes redistribution of heat towards lower latitudes. Future analysis of these and other phenomena with the wider range of CMIP6 FAFMIP AOGCMs will benefit from new diagnostics of temperature and salinity tendencies, which will enable investigation of the model spread in behaviour in terms of physical processes as formulated in the models

Phospho-regulation of ATOH1 Is Required for Plasticity of Secretory Progenitors and Tissue Regeneration

The intestinal epithelium is largely maintained by&nbsp;self-renewing stem cells but with apparently committed progenitors also contributing, particularly following tissue damage. However, the mechanism of, and requirement for, progenitor plasticity in mediating pathological response remain unknown. Here we show that phosphorylation of the transcription factor Atoh1 is required for both the contribution of secretory progenitors to the stem cell pool and for a robust regenerative response. As confirmed by lineage tracing, Atoh1+ cells (Atoh1(WT)CreERT2 mice) give rise to multilineage intestinal clones both in the steady state and&nbsp;after tissue damage. In a phosphomutant Atoh1(9S/T-A)CreERT2 line, preventing phosphorylation of ATOH1 protein acts to promote secretory differentiation and inhibit the contribution of progenitors to self-renewal. Following chemical colitis, Atoh1+ cells of Atoh1(9S/T-A)CreERT2 mice have reduced clonogenicity that affects overall regeneration. Progenitor plasticity maintains robust self-renewal in the intestinal epithelium, and the balance between stem and progenitor fate is directly coordinated by ATOH1 multisite phosphorylation

Early intervention in Portugal: study of professionals’ perceptions

Early intervention (EI) has been characterized by considerable advances in its domain, which has had great repercussions in the implementation of the family-centered approach. These changes have had implications in the practices and in the adoption and learning of new values that should be implemented in EI. This study evaluates the professional perspectives regarding familycentered practices in EI programs in Portugal. The results highlight the importance of effective collaboration and coordination between health, education, and social services and the importance of providing child and family support in a natural context. These results reinforce the need to invest in professional training to improve the quality of services offered to families in EI.Fundação para a Ciência e a Tecnologia (FCT) no âmbito do projecto PEst-OE/CED/UI1661/2014 do CIEd

The trigger system of the NOMAD experiment

The NOMAD trigger system is described in the present paper. It is made up of a largearea plastic scintillator veto system, two trigger scintillator planes inside a 0.4~Tmagnetic field and their associated trigger electronics. Special features of the systemconsist of the use of proximity mesh photomultipliers which allow the trigger scintillators to operate in the magnetic field, and the use of custom-built VME moduleswhich perform the trigger logic decisions, the signal synchronisation and gate generation,event counting and livetime calculations. This paper also includes a description of each of the NOMAD triggers, with their calculated and measured rates, efficiencies and livetimes

Futureproofing [18F]Fludeoxyglucose manufacture at an Academic Medical Center

Abstract Background We recently upgraded our [18F]fludeoxyglucose (FDG) production capabilities with the goal of futureproofing our FDG clinical supply, expanding the number of batches of FDG we can manufacture each day, and improving patient throughput in our nuclear medicine clinic. In this paper we report upgrade of the synthesis modules to the GE FASTLab 2 platform (Phase 1) and cyclotron updates (Phase 2) from both practical and regulatory perspectives. We summarize our experience manufacturing FDG on the FASTLab 2 module with a high-yielding self-shielded niobium (Nb) fluorine-18 target. Results Following installation of Nb targets for production of fluorine-18, a 55 μA beam for 22 min generated 1330 ± 153 mCi of [18F]fluoride. Using these cyclotron beam parameters in combination with the FASTLab 2, activity yields (AY) of FDG were 957 ± 102 mCi at EOS, corresponding to 72% non-corrected AY (n = 235). Our workflow, inventory management and regulatory compliance have been greatly simplified following the synthesis module and cyclotron upgrades, and patient wait times for FDG PET have been cut in half at our nuclear medicine clinic. Conclusions The combination of FASTlab 2 and self-shielded Nb fluorine-18 targets have improved our yield of FDG, and enabled reliable and repeatable manufacture of the radiotracer for clinical use.https://deepblue.lib.umich.edu/bitstream/2027.42/145727/1/41181_2018_Article_48.pd

Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis

The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving a frequency of TARDBP mutations in non-SOD1 FALS of 5% and SALS of 0.4%. Analysis of clinical data identified that patients had typical ALS, with limb or bulbar onset, and showed considerable variation in age of onset and rapidity of disease course. However, all cases had an absence of clinically overt cognitive dysfunction