Not getting in too deep : A practical deep learning approach to routine crystallisation image classification

Using a relatively small training set of ~16 thousand images from macrmolecular crystallisation experiments, we compare classification results obtained with four of the most widely- used convolutional deep-learning network architectures that can be implemented without the need for extensive computational resources. We show that the classifiers have different strengths that can be combined to provide an ensemble classifier achieving a classification accuracy comparable to that obtained by a large consortium initiative. We use eight classes to effectively rank the experimental outcomes, thereby providing detailed information that can be used with routine crystallography experiments to automatically identify crystal forma- tion for drug discovery and pave the way for further exploration of the relationship between crystal formation and crystallisation conditions

Individually customisable non-invasive head immobilisation system for non-human primates with an option for voluntary engagement

Background: Head immobilisation is often necessary for neuroscientific procedures. A number of Non-invasive Head Immobilisation Systems (NHIS) for monkeys are available, but the need remains for a feasible integrated system combining a broad range of essential features. New method: We developed an individualised macaque NHIS addressing several animal welfare and scientific needs. The system comprises a customised-to-fit facemask that can be used separately or combined with a back piece to form a full-head helmet. The system permits presentation of visual and auditory stimuli during immobilisation and provides mouth access for reward. Results: The facemask was incorporated into an automated voluntary training system, allowing the animals to engage with it for increasing periods leading to full head immobilisation. We evaluated the system during performance on several auditory or visual behavioural tasks with testing sessions lasting 1.5–2 h, used thermal imaging to monitor for and prevent pressure points, and measured head movement using MRI. Comparison with existing methods: A comprehensive evaluation of the system is provided in relation to several scientific and animal welfare requirements. Behavioural results were often comparable to those obtained with surgical implants. Cost–benefit analyses were conducted comparing the system with surgical options, highlighting the benefits of implementing the non-invasive option. Conclusions: The system has a number of potential applications and could be an important tool in neuroscientific research, when direct access to the brain for neuronal recordings is not required, offering the opportunity to conduct non-invasive experiments while improving animal welfare and reducing reliance on surgically implanted head posts

The Barley Genome Sequence Assembly Reveals Three Additional Members of the <i>CslF </i>(1,3;1,4)-b-Glucan Synthase Gene Family

An important component of barley cell walls, particularly in the endosperm, is (1,3;1,4)-β-glucan, a polymer that has proven health benefits in humans and that influences processability in the brewing industry. Genes of the cellulose synthase-like (Csl) F gene family have been shown to be involved in (1,3;1,4)-β-glucan synthesis but many aspects of the biosynthesis are still unclear. Examination of the sequence assembly of the barley genome has revealed the presence of an additional three HvCslF genes (HvCslF11, HvCslF12 and HvCslF13) which may be involved in (1,3;1,4)-β-glucan synthesis. Transcripts of HvCslF11 and HvCslF12 mRNA were found in roots and young leaves, respectively. Transient expression of these genes in Nicotiana benthamiana resulted in phenotypic changes in the infiltrated leaves, although no authentic (1,3;1,4)-β-glucan was detected. Comparisons of the CslF gene families in cereals revealed evidence of intergenic recombination, gene duplications and translocation events. This significant divergence within the gene family might be related to multiple functions of (1,3;1,4)-β-glucans in the Poaceae. Emerging genomic and global expression data for barley and other cereals is a powerful resource for characterising the evolution and dynamics of complete gene families. In the case of the CslF gene family, the results will contribute to a more thorough understanding of carbohydrate metabolism in grass cell walls

Ancient DNA Suggests Dwarf and ‘Giant’ Emu Are Conspecific

) is unclear. King Island Emu were mainly distinguished by their much smaller size and a reported darker colour compared to modern Emu. oxidase subunit I (COI) region (1,544 bp), as well as a region of the melanocortin 1 receptor gene (57 bp) were sequenced using a multiplex PCR approach. The results show that haplotypes for King Island Emu fall within the diversity of modern Emu.These data show the close relationship of these emu when compared to other congeneric bird species and indicate that the King Island and modern Emu share a recent common ancestor. King Island emu possibly underwent insular dwarfism as a result of phenotypic plasticity. The close relationship between the King Island and the modern Emu suggests it is most appropriate that the former should be considered a subspecies of the latter. Although both taxa show a close genetic relationship they differ drastically in size. This study also suggests that rates of morphological and neutral molecular evolution are decoupled

Differential IRF8 Transcription Factor Requirement Defines Two Pathways of Dendritic Cell Development in Humans

The formation of mammalian dendritic cells (DCs) is controlled by multiple hematopoietic transcription factors, including IRF8. Loss of IRF8 exerts a differential effect on DC subsets, including plasmacytoid DCs (pDCs) and the classical DC lineages cDC1 and cDC2. In humans, cDC2-related subsets have been described including AXL+ SIGLEC6+ pre-DC, DC2 and DC3. The origin of this heterogeneity is unknown. Using highdimensional analysis, in vitro differentiation, and an allelic series of human IRF8 deficiency, we demonstrated that cDC2 (CD1c+ DC) heterogeneity originates from two distinct pathways of development. The lymphoidprimed IRF8hi pathway, marked by CD123 and BTLA, carried pDC, cDC1, and DC2 trajectories, while the common myeloid IRF8lo pathway, expressing SIRPA, formed DC3s and monocytes. We traced distinct trajectories through the granulocyte-macrophage progenitor (GMP) compartment showing that AXL+ SIGLEC6+ pre-DCs mapped exclusively to the DC2 pathway. In keeping with their lower requirement for IRF8, DC3s expand to replace DC2s in human partial IRF8 deficiency

A comprehensive gene-environment interaction analysis in Ovarian Cancer using genome-wide significant common variants.

As a follow-up to genome-wide association analysis of common variants associated with ovarian carcinoma (cancer), our study considers seven well-known ovarian cancer risk factors and their interactions with 28 genome-wide significant common genetic variants. The interaction analyses were based on data from 9971 ovarian cancer cases and 15,566 controls from 17 case-control studies. Likelihood ratio and Wald tests for multiplicative interaction and for relative excess risk due to additive interaction were used. The top multiplicative interaction was noted between oral contraceptive pill (OCP) use (ever vs. never) and rs13255292 (p value = 3.48 × 10-4 ). Among women with the TT genotype for this variant, the odds ratio for OCP use was 0.53 (95% CI = 0.46-0.60) compared to 0.71 (95%CI = 0.66-0.77) for women with the CC genotype. When stratified by duration of OCP use, women with 1-5 years of OCP use exhibited differential protective benefit across genotypes. However, no interaction on either the multiplicative or additive scale was found to be statistically significant after multiple testing correction. The results suggest that OCP use may offer increased benefit for women who are carriers of the T allele in rs13255292. On the other hand, for women carrying the C allele in this variant, longer (5+ years) use of OCP may reduce the impact of carrying the risk allele of this SNP. Replication of this finding is needed. The study presents a comprehensive analytic framework for conducting gene-environment analysis in ovarian cancer

The 3--D ionization structure of NGC 6818: a Planetary Nebula threatened by recombination

Long-slit NTT+EMMI echellograms of NGC 6818 (the Little Gem) at nine equally spaced position angles, reduced according to the 3-D methodology introduced by Sabbadin et al. (2000a,b), allowed us to derive: the expansion law, the diagnostics and ionic radial profiles, the distance and the central star parameters, the nebular photo-ionization model, the 3-D reconstruction in He II, [O III] and [N II], the multicolor projection and a series of movies. The Little Gem results to be a young (3500 years), optically thin (quasi-thin in some directions) double shell (Mion~0.13 Msun) at a distance of 1.7 kpc, seen almost equatorial on: a tenuous and patchy spherical envelope (r~0.090 pc) encircles a dense and inhomogeneous tri-axial ellipsoid (a/2~0.077 pc, a/b~1.25, b/c~1.15) characterized by a hole along the major axis and a pair of equatorial, thick moustaches. NGC 6818 is at the start of the recombination phase following the luminosity decline of the 0.625 Msun central star, which has recently exhausted the hydrogen shell nuclear burning and is rapidly moving toward the white dwarf domain (log T*~5.22 K; log(L*/Lsun)~3.1). The nebula is destined to become thicker and thicker, with an increasing fraction of neutral, dusty gas in the outermost layers. Only over some hundreds of years the plasma rarefaction due to the expansion will prevail against the slower and slower stellar decline, leading to a gradual re-growing of the ionization front. The exciting star of NGC 6818 (mV~17.06) is a visual binary: a faint, red companion (mV~17.73) appears at 0.09 arcsec in PA=190deg, corresponding to a separation >=150 AU and to an orbital period >=1500 yearsComment: 23 pages, 18 figures, A&A accepted. 12 movies of NGC 6818 are available at http://web.pd.astro.it/sabbadin The paper may also be retrivied at http://web.pd.astro.it/supern/preprints.htm

Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs

Genetically Determined Height and Risk of Non-hodgkin Lymphoma

Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00–1.17, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01–1.31, p = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes