Processing and analyzing multiple genomes alignments with MafFilter

As the number of available genome sequences from both closely related species and individuals withinspecies increased, theoretical and methodological convergences between the fields of phylogenomics andpopulation genomics emerged. Population genomics typically focuses on the analysis of variants, whilephylogenomics heavily relies on genome alignments. However, these are playing an increasingly importantrole in studies at the population level. Multiple genome alignments of individuals are used when structuralvariation is of primary interest and when genome architecture permits to assemblede novogenomesequences. Here I describe MafFilter, a command-line-driven program allowing to process genome align-ments in the Multiple Alignment Format (MAF). Using concrete examples based on publicly availabledatasets, I demonstrate how MafFilter can be used to develop efficient and reproducible pipelines withquality assurance for downstream analyses. I further show how MafFilter can be used to perform both basicand advanced population genomic analyses in order to infer the patterns of nucleotide diversity alonggenomes

Measurement of illumination exposure in postpartum women

BACKGROUND: Low levels of light exposure at critical times are thought to cause seasonal affective disorder. Investigators, in studies demonstrating the usefulness of bright light therapy, also have implicated light's role in non-seasonal depression. The precise cause of postpartum depression has not been delineated, but it seemed possible that new mothers would spend reduced time in daylight. The goal of this study was to examine the levels of illumination experienced by postpartum mothers and to discover any relationship between light exposure and mood levels experienced during the postpartum period. METHODS: Fifteen postpartum women, who did not have any baseline indication of depression, wore a wrist device (Actillume) for 72 hours to measure their exposure to light. At the end of the recording period, they completed a self-reported measure of mood. The mean light exposure of these postpartum women (expressed as the 24-hour average logarithm of illumination in lux) was compared with that of a representative sample of women of comparable age, residence, and seasonal months of recording. Mood levels were then rank-ordered and tested for correlation with light exposure levels. RESULTS: There was no significant difference between the amount of light [log(10)lux] experienced by postpartum (1.01 SD 0.236) and control women (1.06 SD 0.285). Mood was not correlated with illumination in the postpartum sample. CONCLUSIONS: Postpartum women in San Diego did not receive reduced light, nor was low mood related to low illumination

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Heterodimers of photoreceptor-specific nuclear receptor (PNR/NR2E3) and peroxisome proliferator-activated receptor (PPARγ) are disrupted by retinal disease-associated mutations

Photoreceptor-specific nuclear receptor (PNR/NR2E3) and Tailless homolog (TLX/NR2E1) are human orthologs of the NR2E group, a subgroup of phylogenetically related members of the Nuclear Receptor (NR) superfamily of transcription factors. We assessed the ability of these NRs to form heterodimers with other members of the human NRs representing all major subgroups. The TLX ligand binding domain (LBD) did not appear to form homodimers or interact directly with any other NR tested. The PNR LBD was able to form homodimers, but also exhibited robust interactions with the LBDs of PPARγ/NR1C3 and TRβ/NR1A2. The binding of PNR to PPARγ was specific for this paralog, as no interaction was observed with the LBDs of PPARαNR1C1 or PPARδNR1C2. In support of these findings, PPARγ and PNR were found to be co-expressed in human retinal tissue extracts and could be co-immunoprecipitated as a native complex. Selected sequence variants in the PNR LBD associated with human retinopathies, or a mutation in the dimerization region of PPARγ LBD associated with familial partial lipodystrophy type 3, were found to disrupt PNR/PPARγ complex formation. Wild type PNR, but not a PNR309G mutant, was able to repress PPARγ-mediated transcription in reporter assays. In summary our results reveal novel heterodimer interactions in the NR superfamily, suggesting previously unknown functional interactions of PNR with PPARγ and TRβ that have potential importance in retinal development and disease

Decomposers and root feeders interactively affect plant defence in Sinapis alba

Aboveground herbivory is well known to change plant growth and defence. In contrast, effects of soil organisms, acting alone or in concert, on allocation patterns are less well understood. We investigated separate and combined effects of the endogeic earthworm species Aporrectodea caliginosa and the root feeding nematode species Pratylenchus penetrans and Meloidogyne incognita on plant responses including growth and defence metabolite concentrations in leaves of white mustard, Sinapis alba. Soil biota had a strong impact on plant traits, with the intensity varying due to species combinations. Nematode infestation reduced shoot biomass and nitrogen concentration but only in the absence of earthworms. Earthworms likely counteracted the negative effects of nematodes. Infestation with the migratory lesion-nematode P. penetrans combined with earthworms led to increased root length. Earthworm biomass increased in the presence of this species, indicating that these nematodes increased the food resources of earthworms—presumably dead and decaying roots. Nitrogen-based defence compounds, i.e. glucosinolates, did not correlate with nitrogen levels. In the presence of earthworms, concentrations of aromatic glucosinolates in leaves were significantly increased. In contrast, infection with P. penetrans strongly decreased concentrations of glucosinolates (up to 81%). Infestation with the sedentary nematode M. incognita induced aromatic glucosinolates by more than 50% but only when earthworms were also present. Myrosinase activities, glucosinolate-hydrolysing enzymes, were unaffected by nematodes but reduced in the presence of earthworms. Our results document that root-feeding nematodes elicit systemic plant responses in defence metabolites, with the responses varying drastically with nematode species of different functional groups. Furthermore, systemic plant responses are also altered by decomposer animals, such as earthworms, challenging the assumption that induction of plant responses including defence traits is restricted to herbivores. Soil animals even interact and modulate the individual effects on plant growth and plant defence, thereby likely also influencing shoot herbivore attack

Mechanical performance and healing patterns of the novel sirolimus-eluting bioresorbable Fantom scaffold: 6-month and 9-month follow-up by optical coherence tomography in the FANTOM II study

Objectives We aimed to evaluate the mechanical properties and healing patterns 6 and 9 months after implantation of the sirolimus-eluting Fantom bioresorbable scaffold (BRS). Background The Fantom BRS (Reva Medical, San Diego, USA) has differentiating properties including radiopacity, strut thickness of 125 µm, high expansion capacity and has demonstrated favourable mid-term clinical and angiographic outcomes. Methods and results FANTOM II was a prospective, single arm study with implantation of the Fantom BRS in 240 patients with stable angina pectoris. Guidance by optical coherence tomography (OCT) was encouraged and was repeated at 6-month (cohort A) or 9-month follow-up (cohort B). Matched baseline and follow-up OCT recordings were available in 152 patients. In-scaffold mean lumen area in cohort A was 6.8±1.7mm2 and 5.7±1.4mm2 at baseline and follow-up (p<0.0001) and was 7.2±1.6mm2 and 5.6±1.4mm2 in cohort B (p<0.0001). Mean scaffold area remained stable from 7.1±1.5mm2 at baseline to 7.2±1.4mm2 at 6 months (p=0.12), and from 7.4±1.5mm2 to 7.3±1.4mm2 at 9 months. Strut malapposition was median 0.8 (IQR 0.0;3.5)% and 1.8 (IQR 0.3;6.0)% at baseline and was 0.0 (IQR 0.0;0.0)% in both groups at 6-month and 9-month follow-up. Strut tissue coverage was 98.1 (IQR 95.9;99.4)% at 6 months and 98.9 (IQR 98.3;100.0)% at 9 months. Conclusions The novel Fantom BRS had favourable healing patterns at 6-month and 9-month follow-up as malapposition was effectively resolved and strut coverage was almost complete. The scaffold remained stable through follow-up with no signs of systematic late recoil

DNA topoisomerase I and II expression in drug resistantgerm cell tumours

A small number of testicular germ cell tumours are refractory to current chemotherapy regimens. DNA topoisomerase I is the target for several new drugs and a potential candidate treatment for chemorefractory germ cell tumours. DNA topoisomerase IIα is the target for etoposide, which is currently used regularly in germ cell tumour treatment. The expression of DNA topoisomerase I and IIα were therefore assessed immunohistochemically in a range of testicular tumours, especially those with persistent malignant elements on retroperitoneal lymph node dissection. Pre-chemotherapy orchidectomy specimens were matched with post-chemotherapy retroperitoneal lymph node dissections to examine changes in expression. There was considerable variation in the expression of topoisomerase I in different tumour types. Both yolk sac tumours and teratoma, mature showed universal expression of topoisomerase I, while 38% of seminomas and 30% of embryonal carcinomas were positive. Strong topoisomerase IIα expression was found in embryonal carcinoma. There was a negative correlation between topoisomerase I and IIα expression (P=0.004) and downregulation of topoisomerase IIα after chemotherapy (P=0.02). Topoisomerase I expression appears to increase in those cases with residual teratoma, mature, but is largely unchanged in those cases remaining as embryonal carcinoma. These results suggest that topoisomerase I inhibitors may be useful in chemorefractory germ cell tumours, especially yolk sac tumours and where there are unresectable residual teratoma, mature deposits

Gender-related differences in physiologic color space: a functional transcranial Doppler (fTCD) study

Simultaneous color contrast and color constancy are memory processes associated with color vision, however, the gender-related differences of 'physiologic color space' remains unknown. Color processing was studied in 16 (8 men and 8 women) right-handed healthy subjects using functional transcranial Doppler (fTCD) technique. Mean flow velocity (MFV) was recorded in both right (RMCA) and left (LMCA) middle cerebral arteries in dark and white light conditions, and during color (blue and yellow) stimulations. The data was plotted in a 3D quadratic curve fit to derive a 'physiologic color space' showing the effects of luminance and chromatic contrasts. In men, wavelength-differencing of opponent pairs (yellow-blue) was adjudged by changes in the RMCA MFV for Yellow plotted on the Y-axis, and the RMCA MFV for Blue plotted on the X-axis. In women, frequency-differencing for opponent pairs (blue-yellow) was adjudged by changes in the LMCA MFV for Yellow plotted on the Y-axis, and the LMCA MFV for Blue plotted on the X-axis. The luminance effect on the LMCA MFV in response to white light with the highest luminous flux, was plotted on the (Z - axis), in both men and women. The 3D-color space for women was a mirror-image of that for men, and showed enhanced color constancy. The exponential function model was applied to the data in men, while the logarithmic function model was applied to the data in women. Color space determination may be useful in the study of color memory, adaptive neuroplasticity, cognitive impairment in stroke and neurodegenerative diseases

Evidence for Epithelial-Mesenchymal Transition in Cancer Stem Cells of Head and Neck Squamous Cell Carcinoma

Initiation, growth, recurrence, and metastasis of head and neck squamous cell carcinomas (HNSCC) have been related to the behavior of cancer stem cells (CSC) that can be identified by their aldehyde-dehydrogenase-isoform-1 (ALDH1) activity. We quantified and enriched ALDH1+ cells within HNSCC cell lines and subsequently characterized their phenotypical and functional properties like invasion capacity and epithelial-mesenchymal transition (EMT). Spheroid culture enriched CSC from five HNSCC cell lines by up to 5-fold. In spheroid-derived cells (SDC) and the parental monolayer-derived cell line ALDH1, CD44, CD24, E-Cadherin, α-SMA, and Vimentin expression was compared by flow-cytometry and immunofluorescence together with proliferation and cell cycle analysis. Invasion activity was evaluated by Matrigel assay and expression of stemness-related transcription factors (TF) Nanog, Oct3/4, Sox2 and EMT-related genes Snail1 and 2, and Twist by real-time PCR. All cell lines formed spheroids that could self-renew and be serially re-passaged. ALDH1 expression was significantly higher in SDC. ALDH1+ cells showed increased colony-formation. The proportion of cells with a putative CSC marker constellation of CD44+/CD24− was highly variable (0.5% to 96%) in monolayer and spheroid cultures and overlapped in 0%–33% with the CD44+/CD24−/ALDH1+ cell subset. SDC had significantly higher invading activity. mRNA of the stemness-related genes Sox2, Nanog, and Oct3/4 was significantly increased in SDC of all cell lines. Twist was significantly increased in two while Snail2 showed a significant increase in one and a significant decrease in SDC of two cell lines. SDC had a higher G0 phase proportion, showed high-level expression of α-SMA and Vimentin, but significantly decreased E-Cadherin expression. HNSCC-lines harbor potential CSC, characterized by ALDH1 and stemness marker TF expression as well as properties like invasiveness, quiescence, and EMT. CSC can be enriched by anchorage-independent culture techniques, which may be important for the investigation of their contribution to therapy resistance, tumor recurrence and metastasis