Exploring the phases of 3D artificial spin ice: From Coulomb phase to magnetic monopole crystal

Artificial spin-ices consist of lithographic arrays of single-domain magnetic nanowires organised into frustrated lattices. These geometries are usually two-dimensional, allowing a direct exploration of physics associated with frustration, topology and emergence. Recently, three-dimensional geometries have been realised, in which transport of emergent monopoles can be directly visualised upon the surface. Here we carry out an exploration of the three-dimensional artificial spin-ice phase diagram, whereby dipoles are placed within a diamond-bond lattice geometry. We find a rich phase diagram, consisting of a double-charged monopole crystal, a single-charged monopole crystal and conventional spin-ice with pinch points associated with a Coulomb phase. In our experimental demagnetised systems, broken symmetry forces formation of ferromagnetic stripes upon the surface, a configuration that forbids the formation of the lower energy double-charged monopole crystal. Instead, we observe crystallites of single magnetic charge, superimposed upon an ice background. The crystallites are found to form due to the intricate distribution of magnetic charge around a three-dimensional nanostructured vertex, which locally favours monopole formation. Our work suggests that engineered surface energetics can be used to tune the ground state of experimental three-dimensional ASI systems

Cobalt ferrite nanoparticles under high pressure

We report by the first time a high pressure X-ray diffraction and Raman spectroscopy study of cobalt ferrite (CoFe2O4) nanoparticles carried out at room temperature up to 17 GPa. In contrast with previous studies of nanoparticles, which proposed the transition pressure to be reduced from 20–27 GPa to 7.5–12.5 GPa (depending on particle size), we found that cobalt ferrite nanoparticles remain in the spinel structure up to the highest pressure covered by our experiments. In addition, we report the pressure dependence of the unit-cell parameter and Raman modes of the studied sample. We found that under quasi-hydrostatic conditions, the bulk modulus of the nanoparticles (B0 = 204 GPa) is considerably larger than the value previously reported for bulk CoFe2O4 (B0 = 172 GPa). In addition, when the pressure medium becomes non-hydrostatic and deviatoric stresses affect the experiments, there is a noticeable decrease of the compressibility of the studied sample (B0 = 284 GPa). After decompression, the cobalt ferrite lattice parameter does not revert to its initial value, evidencing a unit cell contraction after pressure was removed. Finally, Raman spectroscopy provides information on the pressure dependence of all Raman-active modes and evidences that cation inversion is enhanced by pressure under non-hydrostatic conditions, being this effect not fully reversible.Fil: Saccone, Fabio Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnologías y Ciencias de la Ingeniería; ArgentinaFil: Ferrari, Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnologías y Ciencias de la Ingeniería; ArgentinaFil: Errandonea, Daniel. Universidad de Valencia; EspañaFil: Florencia Grinblat. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnologías y Ciencias de la Ingeniería; ArgentinaFil: Bilovol, Vitaliy. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnologías y Ciencias de la Ingeniería; ArgentinaFil: Agouram, S.. Universidad de Valencia; Españ

Vitamin E bioavailability : past and present insights

Animal health and production in dairy cows. Cow milk is considered as a remarkable source of bioactive components promoting human health, which has renewed interest in the effects of vitamin E supplementation on its nutritional value, sensory quality and shelf life. Thus, defining relative bioavailability, utilisation and transfer into milk of different vita- min E formulations is particularly important to assess the adequate levels of supplementation for animal health and milk quality. In nature vitamin E is present under one isomeric form, RRR \u3b1-tocopherol; when \u3b1-tocopherol is synthe- sized chemically, a racemic mixture of 8 possible isomers of \u3b1-tocopherol in equimolar concentrations is produced (all-rac \u3b1-tocopherol). The different stereoisomers have different biopotencies in humans and livestock; the conversion factor between RRR and all-rac vitamin E was estimated by early studies on the basis of the rat foetal resorption bio- assay, and then extended to other species. Recent advances on the distribution of vitamin E stereoisomers in plasma and tissues have highlighted the need to formulate new conversion factors in dairy cows as well as in humans. On ac- count of this, the present article aims to consider past and recent data related to vitamin E in dairy cow nutrition

Modeling complex genetic and environmental influences on comorbid bipolar disorder with tobacco use disorder

Abstract Background Comorbidity of psychiatric and substance use disorders represents a significant complication in the clinical course of both disorders. Bipolar Disorder (BD) is a psychiatric disorder characterized by severe mood swings, ranging from mania to depression, and up to a 70% rate of comorbid Tobacco Use Disorder (TUD). We found epidemiological evidence consistent with a common underlying etiology for BD and TUD, as well as evidence of both genetic and environmental influences on BD and TUD. Therefore, we hypothesized a common underlying genetic etiology, interacting with nicotine exposure, influencing susceptibility to both BD and TUD. Methods Using meta-analysis, we compared TUD rates for BD patients and the general population. We identified candidate genes showing statistically significant, replicated, evidence of association with both BD and TUD. We assessed commonality among these candidate genes and hypothesized broader, multi-gene network influences on the comorbidity. Using Fisher Exact tests we tested our hypothesized genetic networks for association with the comorbidity, then compared the inferences drawn with those derived from the commonality assessment. Finally, we prioritized candidate SNPs for validation. Results We estimate risk for TUD among BD patients at 2.4 times that of the general population. We found three candidate genes associated with both BD and TUD (COMT, SLC6A3, and SLC6A4) and commonality analysis suggests that these genes interact in predisposing psychiatric and substance use disorders. We identified a 69 gene network that influences neurotransmitter signaling and shows significant over-representation of genes associated with BD and TUD, as well as genes differentially expressed with exposure to tobacco smoke. Twenty four of these genes are known drug targets. Conclusions This work highlights novel bioinformatics resources and demonstrates the effectiveness of using an integrated bioinformatics approach to improve our understanding of complex disease etiology. We illustrate the development and testing of hypotheses for a comorbidity predisposed by both genetic and environmental influences. Consistent with our hypothesis, the selected network models multiple interacting genetic influences on comorbid BD with TUD, as well as the environmental influence of nicotine. This network nominates candidate genes for validation and drug testing, and we offer a panel of SNPs prioritized for follow-up.http://deepblue.lib.umich.edu/bitstream/2027.42/112449/1/12881_2009_Article_575.pd

In search of causal variants: refining disease association signals using cross-population contrasts

<p>Abstract</p> <p>Background</p> <p>Genome-wide association (GWA) using large numbers of single nucleotide polymorphisms (SNPs) is now a powerful, state-of-the-art approach to mapping human disease genes. When a GWA study detects association between a SNP and the disease, this signal usually represents association with a set of several highly correlated SNPs in strong linkage disequilibrium. The challenge we address is to distinguish among these correlated loci to highlight potential functional variants and prioritize them for follow-up.</p> <p>Results</p> <p>We implemented a systematic method for testing association across diverse population samples having differing histories and LD patterns, using a logistic regression framework. The hypothesis is that important underlying biological mechanisms are shared across human populations, and we can filter correlated variants by testing for heterogeneity of genetic effects in different population samples. This approach formalizes the descriptive comparison of p-values that has typified similar cross-population fine-mapping studies to date. We applied this method to correlated SNPs in the cholinergic nicotinic receptor gene cluster <it>CHRNA5-CHRNA3-CHRNB4</it>, in a case-control study of cocaine dependence composed of 504 European-American and 583 African-American samples. Of the 10 SNPs genotyped in the r²≥ 0.8 bin for <it>rs16969968</it>, three demonstrated significant cross-population heterogeneity and are filtered from priority follow-up; the remaining SNPs include <it>rs16969968 </it>(heterogeneity p = 0.75). Though the power to filter out rs16969968 is reduced due to the difference in allele frequency in the two groups, the results nevertheless focus attention on a smaller group of SNPs that includes the non-synonymous SNP rs16969968, which retains a similar effect size (odds ratio) across both population samples.</p> <p>Conclusion</p> <p>Filtering out SNPs that demonstrate cross-population heterogeneity enriches for variants more likely to be important and causative. Our approach provides an important and effective tool to help interpret results from the many GWA studies now underway.</p

Nuclear repositioning of the non-translocated HLXB9 allele in the leukaemia cell line GDM-1 harbouring a t(6;7)(q23;q36)

Background/Aims. Transcriptionally active and inactive topologically associated domains (TADs) occupy different areas in the cell nucleus, and chromosomal rearrangements relocating TADs could determine ectopic expression of the repositioned genes. In this study, we investigated the HLXB9 gene in a myeloid leukaemia cell line, GDM-1, known to harbour a rearrangement involving the chromosome 7 with breakpoint distal to HLXB9, highly expressed in these cells. Methods. We used fluorescence in situ hybridisation (FISH) to target the regions involved in the translocation and to distinguish the translocated chromosome from the non-translocated one in interphase nuclei. Results. Two-dimensional (2D) analysis of the interphase FISH data indicated that the two HLXB9 alleles had a different localisation in the cell nuclei, with the translocated allele consistently positioned in the nuclear periphery and the normal one in the more internal portion of the nucleus, known as the transcriptionally active compartment. Conclusion. Our data may indicate that HLXB9 transcripts in GDM-1 cell line do not arise from the allele located in the rearranged chromosome 7, suggesting that regulation of gene expression in cancer cells harbouring chromosomal translocations might be more complex than previously thought, paving the path to further investigations on mechanisms of gene expression

Fetal brain hemodynamics in pregnancies at term: correlation with gestational age, birthweight and clinical outcome

Introduction: The primary aim of this study was to ascertain the strength of association between cerebral blood flow assessed in anterior (ACA), middle (MCA), and posterior (PCA) cerebral arteries and the following clinical outcomes: small for gestational age (SGA), induction of labor (IOL) for oligohydramnios and caesarean section (CS) for nonreassuring fetal status (NRFS) during labor. Material and methods: Retrospective analysis of prospectively collected data on consecutive singleton pregnancies from 40 0/7 to 41 6/7 week of gestation. UA, ACA, MCA, PCA pulsatility index (PI) were measured from 40 weeks of gestations. Furthermore, the ratios between cerebral blood flow and UA (CPR, ACA/UA and PCA/UA) were calculated and correlated with the observed outcomes. Results: Two hundred twenty-four singleton pregnancies were included in the study. Mean PI of either ACA (p = .04), MCA (p = .008), and PCA (p = .003) were lower in the SGA compared to non-SGA group; furthermore, mean PCA PI was significantly lower than MCA PI (p = .04). Furthermore, CPR (p = .016), ACA/UA (p = .02), and PCA/UA (p = .003) were significantly lower in the SGA group compared to controls. UA, ACA, MCA, and PCA PI were higher in women undergoing IOL for oligohydramnios compared to controls. Logistic regression analysis showed that CPR and PCA/UA ratio were independently associated with SGA. SGA, ACA PI, and ACA/UA were independently associated with CS for NRFS. Finally, birthweight centile, were independently associated with IOL oligohydramnios. Despite this, the predictive accuracy of Doppler in detecting any of the explored outcome was only poor to moderate. Conclusion: Redistribution of cerebral blood flow at term is significantly associated with SGA, IOL for oligohydramnios and CS for NRFS in labor. However, the predictive accuracy of Doppler at term is only poor to moderate, thus advising against its use in clinical practice as a standalone screening test for adverse perinatal outcome in pregnancies at term. Key Message Redistribution of cerebral blood flow at term is significantly associated with SGA, IOL for oligohydramnios and CS for NRFS in labor

From FISH to Hi-C: the chromatin architecture of the chromosomal region 7q36.3, frequently rearranged in leukemic cells, is evolutionary conserved

Data Availability Statement: FISH data are available on request from the corresponding authors. Hi- C data are in the references [5,7,23,24,26], and visible in the Juicebox software version 1.5.2 from the Broad Institute and Aiden Lab (https://aidenlab.org/juicebox/ accessed on 16 June 2018) referenced in [7,32].© 2021 by the authors. FISH and Hi-C methods are largely used to investigate the three-dimensional organization of the genome in the cell nucleus, and are applied here to study the organization of genes (LMBR1, NOM1, MNX1, UBE3C, PTPRN2) localized in the human 7q36.3 band. This region contains the MNX1 gene, which is normally not expressed in human lymphocytes beyond embryonic development. However, this homeobox gene is frequently activated in leukemic cells and its expression is associated with an altered gene positioning in the leukemia cell nuclei. In this study, we used FISH on 3D-preserved nuclei to investigate the nuclear positioning of MNX1 in the leukemia-derived cell line K562. Of the five copies of the MNX1 gene present n K562, four alleles were positioned in the nuclear periphery and only one in the nuclear interior. Using the Juicebox’s Hi-C dataset, we identified five chromatin loops in the 7q36.3 band, with different extensions related to the size and orientation of the genes located here, and independent from their expression levels. We identified similar loops in 11 human and 3 mouse cell lines, showing that these loops are highly conserved in different human cell lines and during evolution. Moreover, the chromatin loop organization is well conserved also during neuronal cell differentiation, showing consistency in genomic organization of this region in development. In this report, we show that FISH and Hi-C are two different approaches that complement one another and together give complete information on the nuclear organization of specific chromosomal regions in different conditions, including cellular differentiation and genetic diseases.Research Plan PIACERI L.3 Starting Grant from Department of Biological, Geological and Environmental Sciences, University of Catania to C.F

Genetic and pharmacological regulation of the endocannabinoid CB1 receptor in Duchenne muscular dystrophy

The endocannabinoid system refers to a widespread signaling system and its alteration is implicated in a growing number of human diseases. However, the potential role of endocannabinoids in skeletal muscle disorders remains unknown. Here we report the role of the endocannabinoid CB1 receptors in Duchenne's muscular dystrophy. In murine and human models, CB1 transcripts show the highest degree of expression at disease onset, and then decline overtime. Similar changes are observed for PAX7, a key regulator of muscle stem cells. Bioinformatics and biochemical analysis reveal that PAX7 binds and upregulates the CB1 gene in dystrophic more than in healthy muscles. Rimonabant, an antagonist of CB1, promotes human satellite cell differentiation in vitro, increases the number of regenerated myofibers, and prevents locomotor impairment in dystrophic mice. In conclusion, our study uncovers a PAX7-CB1 cross talk potentially exacerbating DMD and highlights the role of CB1 receptors as target for potential therapies

Use of routine ureteral stents in cesarean hysterectomy for placenta accreta

OBJECTIVE: To evaluate benefits of use of ureteral stents in association with cesarean hysterectomy in case of placenta accreta. METHODS: This was a single center, cohort study. Clinical records of singleton pregnancies with placenta accreta who underwent cesarean hysterectomy were included in the study. For this study, pregnancies with diagnoses of placenta accreta, increta, or percreta were considered under the umbrella term of placenta accreta. For all women with placenta accreta, delivery was planned via cesarean hysterectomy at 340-356 weeks, without any attempt to remove the placenta. Reasons for earlier delivery included vaginal bleeding and spontaneous onset of labor. The primary outcome was the incidence of unintentional urinary tract injury. Outcomes were compared in a cohort of women who had planned the placement of ureteral stents and in those who did not. RESULTS: Forty-four singleton gestations with confirmed placenta accreta at the time of cesarean hysterectomy were included in the study. Twenty-four (54.5%) of the included women had the placing of ureteral stents prior to cesarean, while 20 (45.5%) did not. At histological confirmation, most of them had placenta accreta (17/44, 38.6%), 14 placenta increta (31.8%), and 13 placenta percreta (29.6%). Urinary tract injuries occurred in eight cases (18.2%), six in the ureteral stents and two in the non-ureteral stents group (25 versus 10%; p = .21). All the injuries were bladder injuries, while no cases of ureteral injury were recorded. All injuries were recognized intraoperatively. CONCLUSION: In case of placenta accreta, the use of ureteral stents in association with cesarean hysterectomy does not reduce the risk of urinary tract injury