Bulk properties of the van der Waals hard ferromagnet VI3

We present comprehensive measurements of the structural, magnetic, and electronic properties of layered van der Waals ferromagnet VI3 down to low temperatures. Despite belonging to a well-studied family of transition-metal trihalides, this material has received very little attention. We outline, from high-resolution powder x-ray diffraction measurements, a corrected room-temperature crystal structure to that previously proposed and uncover a structural transition at 79 K, also seen in the heat capacity. Magnetization measurements confirm VI3 to be a hard ferromagnet (9.1 kOe coercive field at 2 K) with a high degree of anisotropy, and the pressure dependence of the magnetic properties provide evidence for the two-dimensional nature of the magnetic order. Optical and electrical transport measurements show this material to be an insulator with an optical band gap of 0.67 eV - the previous theoretical predictions of d-band metallicity then lead us to believe VI3 to be a correlated Mott insulator. Our latest band-structure calculations support this picture and show good agreement with the experimental data. We suggest VI3 to host great potential in the thriving field of low-dimensional magnetism and functional materials, together with opportunities to study and make use of low-dimensional Mott physics

miR-93/miR-106b/miR-375-CIC-CRABP1: a novel regulatory axis in prostate cancer progression

Capicua (CIC) has been implicated in pathogenesis of spinocerebellar ataxia type-1 (SCA1) neurodegenerative disease and some types of cancer; however, the role of CIC in prostate cancer remains unknown. Here we show that CIC suppresses prostate cancer progression. CIC expression was markedly decreased in human prostatic carcinoma. CIC overexpression suppressed prostate cancer cell proliferation, invasion, and migration, whereas CIC RNAi exerted opposite effects. We found that knock-down of CIC derepresses expression of ETV5 and CRABP1 in LNCaP and PC-3 cells, respectively, thereby promoting cell proliferation and invasion. We also discovered that miR-93, miR-106b, and miR-375, which are known to be frequently overexpressed in prostate cancer patients, cooperatively down-regulate CIC levels to promote cancer progression. Altogether, we suggest miR-93/miR-106b/miR-375-CIC-CRABP1 as a novel key regulatory axis in prostate cancer progression.113324Ysciescopu

Effects of delayed remote ischemic preconditioning on peri-operative myocardial injury in patients undergoing cardiac surgery - A randomized controlled trial

BACKGROUND: Remote ischemic preconditioning (RIPC) has two time windows for organ protection: acute and delayed. Previous studies have mainly focused on the acute time window to evaluate organ protection by RIPC. We evaluated myocardial protection by delayed RIPC in adult patients undergoing cardiac surgery. METHODS: A total of 160 adult patients undergoing cardiac surgery with cardiopulmonary bypass were randomized to receive either delayed RIPC (four cycles of 5 min of ischemia followed by 5 min of reperfusion by inflation to 200 mm Hg and deflation of a blood pressure cuff on the upper arm) or the control treatment 24–48 h before surgery. The primary endpoint was post-operative troponin I levels serially measured for 72 h. Secondary endpoints included post-operative serum creatinine levels, acute kidney injury, and composite complications. RESULTS: There were no significant differences in post-operative troponin I values. The incidence of acute kidney injury, defined by the Acute Kidney Injury Network staging system, was lower in the delayed RIPC group compared to the control group (30.0% vs. 47.5%; relative risk, 0.768; 95% confidence interval, 0.599–0.985; p = 0.023). Moreover, the occurrence of composite complications was lower in the delayed RIPC group compared with the control group (65.0% vs. 81.3%; relative risk, 0.536; 95% confidence interval, 0.311–0.924; p = 0.020). CONCLUSIONS: While RIPC did not provide cardioprotective effects in patients undergoing cardiac surgery, it appeared to reduce acute kidney injury, as well as the rate of composite complications

Primary cilia elongation in response to interleukin-1 mediates the inflammatory response

Primary cilia are singular, cytoskeletal organelles present in the majority of mammalian cell types where they function as coordinating centres for mechanotransduction, Wnt and hedgehog signalling. The length of the primary cilium is proposed to modulate cilia function, governed in part by the activity of intraflagellar transport (IFT). In articular cartilage, primary cilia length is increased and hedgehog signaling activated in osteoarthritis (OA). Here, we examine primary cilia length with exposure to the quintessential inflammatory cytokine interleukin-1 (IL-1), which is up-regulated in OA. We then test the hypothesis that the cilium is involved in mediating the downstream inflammatory response. Primary chondrocytes treated with IL-1 exhibited a 50 % increase in cilia length after 3 h exposure. IL-1-induced cilia elongation was also observed in human fibroblasts. In chondrocytes, this elongation occurred via a protein kinase A (PKA)-dependent mechanism. G-protein coupled adenylate cyclase also regulated the length of chondrocyte primary cilia but not downstream of IL-1. Chondrocytes treated with IL-1 exhibit a characteristic increase in the release of the inflammatory chemokines, nitric oxide and prostaglandin E2. However, in cells with a mutation in IFT88 whereby the cilia structure is lost, this response to IL-1 was significantly attenuated and, in the case of nitric oxide, completely abolished. Inhibition of IL-1-induced cilia elongation by PKA inhibition also attenuated the chemokine response. These results suggest that cilia assembly regulates the response to inflammatory cytokines. Therefore, the cilia proteome may provide a novel therapeutic target for the treatment of inflammatory pathologies, including OA

MultiMetEval: comparative and multi-objective analysis of genome-scale metabolic models

Comparative metabolic modelling is emerging as a novel field, supported by the development of reliable and standardized approaches for constructing genome-scale metabolic models in high throughput. New software solutions are needed to allow efficient comparative analysis of multiple models in the context of multiple cellular objectives. Here, we present the user-friendly software framework Multi-Metabolic Evaluator (MultiMetEval), built upon SurreyFBA, which allows the user to compose collections of metabolic models that together can be subjected to flux balance analysis. Additionally, MultiMetEval implements functionalities for multi-objective analysis by calculating the Pareto front between two cellular objectives. Using a previously generated dataset of 38 actinobacterial genome-scale metabolic models, we show how these approaches can lead to exciting novel insights. Firstly, after incorporating several pathways for the biosynthesis of natural products into each of these models, comparative flux balance analysis predicted that species like Streptomyces that harbour the highest diversity of secondary metabolite biosynthetic gene clusters in their genomes do not necessarily have the metabolic network topology most suitable for compound overproduction. Secondly, multi-objective analysis of biomass production and natural product biosynthesis in these actinobacteria shows that the well-studied occurrence of discrete metabolic switches during the change of cellular objectives is inherent to their metabolic network architecture. Comparative and multi-objective modelling can lead to insights that could not be obtained by normal flux balance analyses. MultiMetEval provides a powerful platform that makes these analyses straightforward for biologists. Sources and binaries of MultiMetEval are freely available from https://github.com/PiotrZakrzewski/MetEv​al/downloads

Scans for signatures of selection in Russian cattle breed genomes reveal new candidate genes for environmental adaptation and acclimation

Domestication and selective breeding has resulted in over 1000 extant cattle breeds. Many of these breeds do not excel in important traits but are adapted to local environments. These adaptations are a valuable source of genetic material for efforts to improve commercial breeds. As a step toward this goal we identified candidate regions to be under selection in genomes of nine Russian native cattle breeds adapted to survive in harsh climates. After comparing our data to other breeds of European and Asian origins we found known and novel candidate genes that could potentially be related to domestication, economically important traits and environmental adaptations in cattle. The Russian cattle breed genomes contained regions under putative selection with genes that may be related to adaptations to harsh environments (e.g., AQP5, RAD50, and RETREG1). We found genomic signatures of selective sweeps near key genes related to economically important traits, such as the milk production (e.g., DGAT1, ABCG2), growth (e.g., XKR4), and reproduction (e.g., CSF2). Our data point to candidate genes which should be included in future studies attempting to identify genes to improve the extant breeds and facilitate generation of commercial breeds that fit better into the environments of Russia and other countries with similar climates

Effects of Increasing Energy or Lysine in Soybean Meal-Based Diets on Early and Late Finishing Pig Performance

A total of 2,265 finishing pigs (337 × 1050 PIC; initially 110.7 ± 6.14 lb) were used in two 28-d trials to determine the effect of increasing energy or lysine in soybean meal-based diets on early and late finishing pig performance. Pigs were housed in mixed gender pens with 27 pigs per pen and 21 pens per treatment. Soybean meal (SBM) NE values used in diet formulation were either 946 kcal/lb (78% NE of corn; NRC)3 or 1,212 kcal/lb (100% NE of corn). The treatments were structured as a completely randomized design. Treatments consisted of: 1) a diet containing a high level of SBM which was estimated at 100% NE of corn (High SBM); 2) a diet containing a low level of SBM which was estimated at 100% NE of corn with added feed-grade amino acids (Low SBM); 3) a diet containing a low level of SBM which was estimated at 78% NE of corn with added fat (Low SBM w/fat) to equal the NE in diets 1 and 2; and 4) a diet containing a low level of SBM which was estimated at 100% NE of corn with increased feed-grade AA and increased Lys:NE (Low SBM w/AA). Following the 28-d growth trial in the early finishing phase, pigs were fed a common diet for approximately 30 d. Pens were then randomly allotted to 1 of the same 4 treatments for the late finishing phase (initially 251.5 ± 7.40 lb BW). For both experiments, pigs were weighed and feed disappearance was measured every 14 d to determine ADG, ADFI, F/G, and caloric efficiency (CE). In the early finishing study, there were no differences in ADG (P \u3e 0.10), but pigs fed a low level of SBM with increased feed-grade AA and increased Lys:NE (Low SBM w/AA) had increased (P \u3c 0.05) ADFI compared to pigs fed a high level of SBM (High SBM). The increased ADFI without increased ADG resulted in poorer F/G (P \u3c 0.05) in pigs fed a low level of SBM with increased feed-grade AA and increased Lys:NE (Low SBM w/AA) compared to pigs fed a low level of SBM with added fat (Low SBM w/fat). For CE, pigs fed a low level of SBM with added fat (Low SBM w/fat) had improved (P \u3c 0.05) CE compared to pigs fed a low level of SBM with increased feed-grade AA and increased Lys:NE (Low SBM w/AA). In the late finishing study, there was a tendency (P = 0.092) for a treatment effect on F/G where pigs fed the High SBM diet had the best F/G, but there was not a significant difference between any two treatments when using a Tukey multiple comparison adjustment (P \u3e 0.05). There was no evidence (P \u3e 0.10) for a difference in ADG, ADFI, or CE. Based on the performance of pigs fed the low level of SBM with increased AA and increased Lys:NE (Low SBM w/AA), the lost performance of low SBM diets is not due to a lower Lys:Cal ratio that results when NE is underestimated. Using caloric efficiency, SBM is estimated to contain 94% of the NE of corn based on results of the early finishing study and 125% of the NE of corn based on results of the late finishing study

A hysteretic multiscale formulation for nonlinear dynamic analysis of composite materials

This article has been made available through the Brunel Open Access Publishing Fund.A new multiscale finite element formulation is presented for nonlinear dynamic analysis of heterogeneous structures. The proposed multiscale approach utilizes the hysteretic finite element method to model the microstructure. Using the proposed computational scheme, the micro-basis functions, that are used to map the microdisplacement components to the coarse mesh, are only evaluated once and remain constant throughout the analysis procedure. This is accomplished by treating inelasticity at the micro-elemental level through properly defined hysteretic evolution equations. Two types of imposed boundary conditions are considered for the derivation of the multiscale basis functions, namely the linear and periodic boundary conditions. The validity of the proposed formulation as well as its computational efficiency are verified through illustrative numerical experiments

Fabrication of Porous Anodic Alumina with Ultrasmall Nanopores

Anodization of Al foil under low voltages of 1–10 V was conducted to obtain porous anodic aluminas (PAAs) with ultrasmall nanopores. Regular nanopore arrays with pore diameter 6–10 nm were realized in four different electrolytes under 0–30°C according to the AFM, FESEM, TEM images and current evolution curves. It is found that the pore diameter and interpore distance, as well as the barrier layer thickness, are not sensitive to the applied potentials and electrolytes, which is totally different from the rules of general PAA fabrication. The brand-new formation mechanism has been revealed by the AFM study on the samples anodized for very short durations of 2–60 s. It is discovered for the first time that the regular nanoparticles come into being under 1–10 V at the beginning of the anodization and then serve as a template layer dominating the formation of ultrasmall nanopores. Under higher potentials from 10 to 40 V, the surface nanoparticles will be less and less and nanopores transform into general PAAs

ChromaSig: A Probabilistic Approach to Finding Common Chromatin Signatures in the Human Genome

Computational methods to identify functional genomic elements using genetic information have been very successful in determining gene structure and in identifying a handful of cis-regulatory elements. But the vast majority of regulatory elements have yet to be discovered, and it has become increasingly apparent that their discovery will not come from using genetic information alone. Recently, high-throughput technologies have enabled the creation of information-rich epigenetic maps, most notably for histone modifications. However, tools that search for functional elements using this epigenetic information have been lacking. Here, we describe an unsupervised learning method called ChromaSig to find, in an unbiased fashion, commonly occurring chromatin signatures in both tiling microarray and sequencing data. Applying this algorithm to nine chromatin marks across a 1% sampling of the human genome in HeLa cells, we recover eight clusters of distinct chromatin signatures, five of which correspond to known patterns associated with transcriptional promoters and enhancers. Interestingly, we observe that the distinct chromatin signatures found at enhancers mark distinct functional classes of enhancers in terms of transcription factor and coactivator binding. In addition, we identify three clusters of novel chromatin signatures that contain evolutionarily conserved sequences and potential cis-regulatory elements. Applying ChromaSig to a panel of 21 chromatin marks mapped genomewide by ChIP-Seq reveals 16 classes of genomic elements marked by distinct chromatin signatures. Interestingly, four classes containing enrichment for repressive histone modifications appear to be locally heterochromatic sites and are enriched in quickly evolving regions of the genome. The utility of this approach in uncovering novel, functionally significant genomic elements will aid future efforts of genome annotation via chromatin modifications